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  • Risk Factors for Severe Hypoglycemia in Black and White Adults With Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study
    Diabetes Care (IF 11.857) Pub Date : 2017-09-18
    Alexandra K. Lee; Clare J. Lee; Elbert S. Huang; A. Richey Sharrett; Josef Coresh; Elizabeth Selvin

    OBJECTIVE Severe hypoglycemia is a rare but important complication of type 2 diabetes. Few studies have examined the epidemiology of hypoglycemia in a community-based population. RESEARCH DESIGN AND METHODS We included 1,206 Atherosclerosis Risk in Communities (ARIC) Study participants with diagnosed diabetes (baseline, 1996–1998). Severe hypoglycemic events were identified through 2013 by ICD-9 codes from claims for hospitalizations, emergency department visits, and ambulance use. We used Cox regression to evaluate risk factors for severe hypoglycemia. RESULTS The mean age of participants was 64 years, 32% were black and 54% were female. During a median follow-up period of 15.2 years, there were 185 severe hypoglycemic events. Important risk factors after multivariable adjustment were as follows: age (per 5 years: hazard ratio [HR] 1.24; 95% CI 1.07–1.43), black race (HR 1.39; 95% CI 1.02–1.88), diabetes medications (any insulin use vs. no medications: HR 3.00; 95% CI 1.71–5.28; oral medications only vs. no medications: HR 2.20; 95% CI 1.28–3.76), glycemic control (moderate vs. good: HR 1.78; 95% CI 1.11–2.83; poor vs. good: HR 2.62; 95% CI 1.67–4.10), macroalbuminuria (HR 1.95; 95% CI 1.23–3.07), and poor cognitive function (Digit Symbol Substitution Test z score: HR 1.57; 95% CI 1.33–1.84). In an analysis of nontraditional risk factors, low 1,5-anhydroglucitol, difficulty with activities of daily living, Medicaid insurance, and antidepressant use were positively associated with severe hypoglycemia after multivariate adjustment. CONCLUSIONS Poor glycemic control, glycemic variability as captured by 1,5-anhydroglucitol, kidney damage, and measures of cognitive and functional impairments were strongly associated with increased risk of severe hypoglycemia. These factors should be considered in hypoglycemia risk assessments when individualizing diabetes care for older adults.

    更新日期:2017-09-19
  • Diabetes, Prediabetes, and Brain Volumes and Subclinical Cerebrovascular Disease on MRI: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)
    Diabetes Care (IF 11.857) Pub Date : 2017-09-12
    Andrea L.C. Schneider; Elizabeth Selvin; A. Richey Sharrett; Michael Griswold; Josef Coresh; Clifford R. Jack; David Knopman; Thomas Mosley; Rebecca F. Gottesman

    OBJECTIVE To examine the associations of prediabetes, diabetes, and diabetes severity (as assessed by HbA1c and diabetes duration) with brain volumes and vascular pathology on brain MRI and to assess whether the associations of diabetes with brain volumes are mediated by brain vascular pathology. RESEARCH DESIGN AND METHODS Cross-sectional study of 1,713 participants in the Atherosclerosis Risk in Communities Neurocognitive Study (mean age 75 years, 60% female, 27% black, 30% prediabetes, and 35% diabetes) who underwent 3T brain MRI scans in 2011–2013. Participants were categorized by diabetes-HbA1c status as without diabetes (<5.7% [reference]), with prediabetes (5.7 to <6.5%), and with diabetes ([defined as prior diagnosis or HbA1c ≥6.5%] <7.0% vs. ≥7.0%), with further stratification by diabetes duration (<10 vs. ≥10 years). RESULTS In adjusted analyses, compared with participants without diabetes and HbA1c <5.7%, participants with prediabetes and those with diabetes and HbA1c <7.0% did not have significantly different brain volumes or vascular pathology (all P > 0.05), but those with diabetes and HbA1c ≥7.0% had smaller total brain volume (β −0.20 SDs, 95% CI −0.31, −0.09), smaller regional brain volumes (including frontal, temporal, occipital, and parietal lobes; deep gray matter; Alzheimer disease signature region; and hippocampus [all P < 0.05]), and increased burden of white matter hyperintensities (WMH) (P = 0.016). Among participants with diabetes, those with HbA1c ≥7.0% had smaller total and regional brain volumes and an increased burden of WMH (all P < 0.05) compared with those with HbA1c <7.0%. Similarly, participants with longer duration of diabetes (≥10 years) had smaller brain volumes and higher burden of lacunes (all P < 0.05) than those with a diabetes duration <10 years. We found no evidence for mediation by WMH in associations of diabetes with smaller brain volumes by structural equation models (all P > 0.05). CONCLUSIONS More-severe diabetes (defined by higher HbA1c and longer disease duration) but not prediabetes or less-severe diabetes was associated with smaller brain volumes and an increased burden of brain vascular pathology. No evidence was found that associations of diabetes with smaller brain volumes are mediated by brain vascular pathology, suggesting that other mechanisms may be responsible for these associations.

    更新日期:2017-09-15
  • Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-09-13
    Francesca Santilli; Paola G. Simeone; Maria T. Guagnano; Marika Leo; Marica T. Maccarone; Augusto Di Castelnuovo; Cristina Sborgia; Riccardo C. Bonadonna; Ermanno Angelucci; Virginia Federico; Stefano Cianfarani; Lamberto Manzoli; Giovanni Davì; Armando Tartaro; Agostino Consoli

    OBJECTIVE Obesity is associated with an increased risk of type 2 diabetes and cardiovascular complications. The risk depends significantly on adipose tissue distribution. Liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We determined whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese subjects with prediabetes or early type 2 diabetes. RESEARCH DESIGN AND METHODS Sixty-two metformin-treated obese subjects with prediabetes or newly diagnosed type 2 diabetes, were randomized to liraglutide (1.8 mg/d) or lifestyle counseling. Changes in SAT and VAT levels (determined by abdominal MRI), insulin sensitivity (according to the Matsuda Index), and β-cell function (β-index) were assessed during a multiple-sampling oral glucose tolerance test; and circulating levels of IGF-I and IGF-II were assessed before and after a comparable weight loss (7% of initial body weight). RESULTS After comparable weight loss, achieved by 20 patients per arm, and superimposable glycemic control, as reflected by HbA1c level (P = 0.60), reduction in VAT was significantly higher in the liraglutide arm than in the lifestyle arm (P = 0.028), in parallel with a greater improvement in β-index (P = 0.021). No differences were observed in SAT reduction (P = 0.64). IGF-II serum levels were significantly increased (P = 0.024) only with liraglutide administration, and the increase in IGF-II levels correlated with both a decrease in VAT (ρ=-0.435, P = 0.056) and an increase in the β-index (ρ = 0.55, P = 0.012). CONCLUSIONS Liraglutide effects on visceral obesity and β-cell function might provide a rationale for using this molecule in obese subjects in an early phase of glucose metabolism dysregulation natural history.

    更新日期:2017-09-14
  • Antihyperglycemic Medications: A Claims-Based Estimate of First-Line Therapy Use Before Initialization of Second-Line Medications
    Diabetes Care (IF 11.857) Pub Date : 2017-08-31
    Yi-Ju Tseng; Gregory Steinberg; Kathe P. Fox; Joanne Armstrong; Kenneth D. Mandl

    OBJECTIVE The American Diabetes Association recommends metformin as first-line therapy for type 2 diabetes. However, nonadherence to antihyperglycemic medication is common, and a clinician could confuse nonadherence with pharmacologic failure, potentially leading to premature prescribing of second-line therapies. We measured metformin use before second-line therapy initialization. RESEARCH DESIGN AND METHODS This retrospective cross-sectional study used unidentifiable member claims data from individuals covered from 2010 to 2015 by Aetna, a U.S. health benefits company. Beneficiaries with two physician claims or one hospitalization with a type 2 diabetes diagnosis were included. Recommended use of metformin was measured by the proportion of days covered over 60 days. Through sensitivity analysis, we varied estimates of the percentage of beneficiaries who used low-cost generic prescription medication programs. RESULTS A total of 52,544 individuals with type 2 diabetes were eligible. Of 22,956 patients given second-line treatment, only 1,875 (8.2%) had evidence of recommended use of metformin in the prior 60 days, and 6,441 (28.0%) had no prior claims evidence of having taken metformin. At the top range of sensitivity, only 49.5% patients could have had recommended use. Patients were more likely to be given an additional second-line antihyperglycemic medication or insulin if they were given their initial second-line medication without evidence of recommended use of metformin (P < 0.001). CONCLUSIONS Despite published guidelines, second-line therapy often is initiated without evidence of recommended use of first-line therapy. Apparent treatment failures, which may in fact be attributable to nonadherence to guidelines, are common. Point-of-care and population-level processes are needed to monitor and improve guideline adherence.

    更新日期:2017-09-13
  • Longitudinal Change in Fasting Blood Glucose and Myocardial Infarction Risk in a Population Without Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-09-08
    Cheng Jin; Shuohua Chen; Anand Vaidya; Yuntao Wu; Zhijun Wu; Frank B. Hu; Penny Kris-Etherton; Shouling Wu; Xiang Gao

    OBJECTIVE To examine the change in fasting blood glucose (FBG) during repeated assessments over time and its potential impact on the risk of developing myocardial infarction (MI). RESEARCH DESIGN AND METHODS This prospective cohort study included 68,297 participants without diabetes (mean age 49 years) who were free of MI, stroke, and cancer prior to or in 2010 (baseline of the current analysis). FBG concentrations were measured in 2006, 2008, and 2010. The FBG trajectories during 2006–2010, the primary exposure of the current study, were identified by latent mixture modeling. Incident MI cases were confirmed via review of medical records by cardiologists. RESULTS We identified five discrete FBG trajectories according to FBG range and changing pattern over time: elevated-stable (n = 3,877), elevated-decreasing (n = 7,060), moderate-increasing (n = 10,298), moderate-stable (n = 40,352), and low-stable (n = 6,710). During 4 years of follow-up, we documented 283 incident MI cases. Relative to the moderate-stable pattern (FBG ranged 4.9 to 5.1 mmol/L), adjusted hazard ratios (HRs) were 1.53 (95% CI 1.04, 2.26) for the elevated-stable pattern (FBG ranged 6.1 to 6.3 mmol/L) and HR 0.61 (95% CI 0.38, 0.98) for the elevated-decreasing pattern (FBG decreased from 6.0 to 5.4 mmol/L), after adjustment for potential confounders such as age, sex, lifestyle factors, obesity, medical history, blood pressure, blood lipids, and C-reactive protein. Consistently, cumulative average and increasing rate of FBG during 2006–2010, but not a single baseline FBG, predicted future risk of MI. CONCLUSIONS We found that discrete FBG trajectories were significantly associated with subsequent risk of MI in individuals without diabetes. These observations suggest that long-term trajectories of FBG may be important for risk prediction of MI and possibly other macrovascular diseases.

    更新日期:2017-09-11
  • Cut Points for Identifying Clinically Significant Diabetes Distress in Adolescents With Type 1 Diabetes Using the PAID-Teen: Results From Diabetes MILES Youth–Australia
    Diabetes Care (IF 11.857) Pub Date : 2017-09-07
    Virginia Hagger; Christel Hendrieckx; Fergus Cameron; Frans Pouwer; Timothy C. Skinner; Jane Speight

    OBJECTIVE To establish cut point(s) for the Problem Areas in Diabetes–Teens (PAID-T) scale to identify adolescents with clinically meaningful, elevated diabetes distress. RESEARCH DESIGN AND METHODS Data were available from the Diabetes Management and Impact for Long-term Empowerment and Success (MILES) Youth–Australia Study, a national survey assessing various psychosocial indicators among self-selected National Diabetes Services Scheme registrants. Participants in the current study (n = 537) were (mean ± SD) 16 ± 2 years old, had type 1 diabetes for 6 ± 4 years, and 62% (n = 334) were girls. They completed measures of diabetes distress (PAID-T) and depressive symptoms (Patient Health Questionnaire for Adolescents) and self-reported their most recent HbA1c and frequency of self-monitoring of blood glucose (SMBG). Relationships between the PAID-T and the psychological and clinical variables were examined to identify a clinically meaningful threshold for elevated diabetes distress. ANOVAs were used to test whether these variables differed by levels of distress. RESULTS Two cut points distinguished none-to-mild (<70), moderate (70–90), and high (>90) diabetes distress. Moderate distress was experienced by 18% of adolescents and high distress by 36%. Mean depressive symptoms, self-reported HbA1c, and SMBG differed significantly across the three levels of diabetes distress (all P < 0.001), with moderate-to-large effect sizes. CONCLUSIONS Using the PAID-T, this study defined two clinically meaningful cut points to distinguish none-to-mild, moderate, and high diabetes distress in adolescents (aged 13–19). Based on these cut points, most respondents experienced at least moderate diabetes distress, which was clinically significant. Establishing thresholds for elevated diabetes distress will aid clinicians and researchers to interpret PAID-T scores, prompt discussion and intervention for those with unmet needs, and enable the effectiveness of interventions to be evaluated.

    更新日期:2017-09-08
  • Plasma Concentrations of Afamin Are Associated With Prevalent and Incident Type 2 Diabetes: A Pooled Analysis in More Than 20,000 Individuals
    Diabetes Care (IF 11.857) Pub Date : 2017-08-10
    Barbara Kollerits; Claudia Lamina; Cornelia Huth; Pedro Marques-Vidal; Stefan Kiechl; Ilkka Seppälä; Jackie Cooper; Steven C. Hunt; Christa Meisinger; Christian Herder; Ludmilla Kedenko; Johann Willeit; Barbara Thorand; Doreen Dähnhardt; Doris Stöckl; Karin Willeit; Michael Roden; Wolfgang Rathmann; Bernhard Paulweber; Annette Peters; Mika Kähönen; Terho Lehtimäki; Olli T. Raitakari; Steve E. Humphries; Peter Vollenweider; Hans Dieplinger; Florian Kronenberg

    OBJECTIVE The human vitamin E–binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in line with observations in transgenic mice. We thus investigated whether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR). RESEARCH DESIGN AND METHODS Individual-level baseline (n = 20,136) and follow-up data (n = 14,017) of eight prospective cohort studies were investigated. Study-level data were combined using random-effects meta-analyses. Main outcomes were prevalent and incident type 2 diabetes, prediabetes, and IR. Discrimination and reclassification of participants was analyzed for incident type 2 diabetes. RESULTS Mean afamin concentrations between studies ranged from 61 to 73 mg/L. The eight studies included 1,398 prevalent and 585 incident cases of type 2 diabetes. Each increase of afamin by 10 mg/L was associated with prevalent type 2 diabetes (odds ratio [OR] 1.19 [95% CI 1.12–1.26], P = 5.96 × 10−8). Afamin was positively associated with IR assessed by HOMA-IR (β 0.110 [95% CI 0.089–0.132], P = 1.37 × 10−23). Most importantly, afamin measured at baseline was an independent predictor for 585 incident cases of type 2 diabetes (OR 1.30 [95% CI 1.23–1.38], P = 3.53 × 10−19) and showed a significant and valuable gain in risk classification accuracy when added to this extended adjustment model. CONCLUSIONS This pooled analysis in >20,000 individuals showed that afamin is strongly associated with IR, prevalence, and incidence of type 2 diabetes independent of major metabolic risk factors or parameters. Afamin might be a promising novel marker for the identification of individuals at high risk for the development of type 2 diabetes.

    更新日期:2017-09-08
  • Pharmacologic Differences of Sulfonylureas and the Risk of Adverse Cardiovascular and Hypoglycemic Events
    Diabetes Care (IF 11.857) Pub Date : 2017-08-30
    Antonios Douros; Hui Yin; Oriana Hoi Yun Yu; Kristian B. Filion; Laurent Azoulay; Samy Suissa

    OBJECTIVE Sulfonylureas have been associated with an increased risk of cardiovascular adverse events and hypoglycemia, but it is unclear if these risks vary with different agents. We assessed whether the risks of acute myocardial infarction, ischemic stroke, cardiovascular death, all-cause mortality, and severe hypoglycemia differ between sulfonylureas grouped according to pancreas specificity and duration of action. RESEARCH DESIGN AND METHODS Using the U.K. Clinical Practice Research Datalink, linked with the Hospital Episodes Statistics and the Office for National Statistics databases, we conducted a cohort study among patients with type 2 diabetes initiating monotherapy with sulfonylureas between 1998 and 2013. Adjusted hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, comparing use of pancreas-nonspecific, long-acting sulfonylureas (glyburide/glimepiride) to pancreas-specific, short-acting sulfonylureas (gliclazide/glipizide/tolbutamide). RESULTS The cohort included 17,604 sulfonylurea initiators (mean [SD] follow-up 1.2 [1.5] years). Compared with specific, short-acting sulfonylureas (15,741 initiators), nonspecific, long-acting sulfonylureas (1,863 initiators) were not associated with an increased risk of acute myocardial infarction (HR 0.86; CI 0.55–1.34), ischemic stroke (HR 0.92; CI 0.59–1.45), cardiovascular death (HR 1.01; CI 0.72–1.40), or all-cause mortality (HR 0.81; CI 0.66–1.003), but with an increased risk of severe hypoglycemia (HR 2.83; CI 1.64–4.88). CONCLUSIONS The nonspecific, long-acting sulfonylureas glyburide and glimepiride do not have an increased risk of cardiovascular adverse events compared with the specific, short-acting sulfonylureas gliclazide, glipizide, and tolbutamide. However, nonspecific, long-acting sulfonylureas glyburide and glimepiride have an increased risk of severe hypoglycemia.

    更新日期:2017-09-08
  • Incidence, Demographics, and Clinical Characteristics of Diabetes of the Exocrine Pancreas (Type 3c): A Retrospective Cohort Study
    Diabetes Care (IF 11.857) Pub Date : 2017-08-31
    Chris Woodmansey; Andrew P. McGovern; Katherine A. McCullough; Martin B. Whyte; Neil M. Munro; Ana C. Correa; Piers A.C. Gatenby; Simon A. Jones; Simon de Lusignan

    OBJECTIVE This study was conducted to describe the incidence of diabetes following pancreatic disease, assess how these patients are classified by clinicians, and compare clinical characteristics with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS Primary care records in England (n = 2,360,631) were searched for incident cases of adult-onset diabetes between 1 January 2005 and 31 March 2016. We examined demographics, diabetes classification, glycemic control, and insulin use in those with and without pancreatic disease (subcategorized into acute pancreatitis or chronic pancreatic disease) before diabetes diagnosis. Regression analysis was used to control for baseline potential risk factors for poor glycemic control (HbA1c ≥7% [53 mmol/mol]) and insulin requirement. RESULTS We identified 31,789 new diagnoses of adult-onset diabetes. Diabetes following pancreatic disease (2.59 [95% CI 2.38–2.81] per 100,000 person-years) was more common than type 1 diabetes (1.64 [1.47–1.82]; P < 0.001). The 559 cases of diabetes following pancreatic disease were mostly classified by clinicians as type 2 diabetes (87.8%) and uncommonly as diabetes of the exocrine pancreas (2.7%). Diabetes following pancreatic disease was diagnosed at a median age of 59 years and BMI of 29.2 kg/m2. Diabetes following pancreatic disease was associated with poor glycemic control (adjusted odds ratio, 1.7 [1.3–2.2]; P < 0.001) compared with type 2 diabetes. Insulin use within 5 years was 4.1% (3.8–4.4) with type 2 diabetes, 20.9% (14.6–28.9) with diabetes following acute pancreatitis, and 45.8% (34.2–57.9) with diabetes following chronic pancreatic disease. CONCLUSIONS Diabetes of the exocrine pancreas is frequently labeled type 2 diabetes but has worse glycemic control and a markedly greater requirement for insulin.

    更新日期:2017-09-08
  • Dysglycemia and Index60 as Prediagnostic End Points for Type 1 Diabetes Prevention Trials
    Diabetes Care (IF 11.857) Pub Date : 2017-08-24
    Brandon M. Nathan; David Boulware; Susan Geyer; Mark A. Atkinson; Peter Colman; Robin Goland; William Russell; John M. Wentworth; Darrell M. Wilson; Carmella Evans-Molina; Diane Wherrett; Jay S. Skyler; Antoinette Moran; Jay M. Sosenko; the Type 1 Diabetes TrialNet and Diabetes Prevention Trial–Type 1 Study Groups

    OBJECTIVE We assessed dysglycemia and an Index60 ≥1.00 (on the basis of fasting C-peptide, 60-min glucose, and 60-min C-peptide levels) as prediagnostic end points for type 1 diabetes among Type 1 Diabetes TrialNet Pathway to Prevention Study participants. RESEARCH DESIGN AND METHODS Two cohorts were analyzed: 1) baseline normoglycemic oral glucose tolerance tests (OGTTs) with an incident dysglycemic OGTT and 2) baseline Index60 <1.00 OGTTs with an incident Index60 ≥1.00 OGTT. Incident dysglycemic OGTTs were divided into those with (DYS/IND+) and without (DYS/IND−) concomitant Index60 ≥1.00. Incident Index60 ≥1.00 OGTTs were divided into those with (IND/DYS+) and without (IND/DYS−) concomitant dysglycemia. RESULTS The cumulative incidence for type 1 diabetes was greater after IND/DYS− than after DYS/IND− (P < 0.01). Within the normoglycemic cohort, the cumulative incidence of type 1 diabetes was higher after DYS/IND+ than after DYS/IND− (P < 0.001), whereas within the Index60 <1.00 cohort, the cumulative incidence after IND/DYS+ and after IND/DYS− did not differ significantly. Among nonprogressors, type 1 diabetes risk at the last OGTT was greater for IND/DYS− than for DYS/IND− (P < 0.001). Hazard ratios (HRs) of DYS/IND− with age and 30–0-min C-peptide were positive (P < 0.001 for both), whereas HRs of type 1 diabetes with these variables were inverse (P < 0.001 for both). In contrast, HRs of IND/DYS− and type 1 diabetes with age and 30–0-min C-peptide were consistent (all inverse [P < 0.01 for all]). CONCLUSIONS The findings suggest that incident dysglycemia without Index60 ≥1.00 is a suboptimal prediagnostic end point for type 1 diabetes. Measures that include both glucose and C-peptide levels, such as Index60 ≥1.00, appear better suited as prediagnostic end points.

    更新日期:2017-09-08
  • Closed Loop Control During Intense Prolonged Outdoor Exercise in Adolescents With Type 1 Diabetes: The Artificial Pancreas Ski Study
    Diabetes Care (IF 11.857) Pub Date : 2017-08-30
    Marc D. Breton; Daniel R. Cherñavvsky; Gregory P. Forlenza; Mark D. DeBoer; Jessica Robic; R. Paul Wadwa; Laurel H. Messer; Boris P. Kovatchev; David M. Maahs

    OBJECTIVE Intense exercise is a major challenge to the management of type 1 diabetes (T1D). Closed loop control (CLC) systems (artificial pancreas) improve glycemic control during limited intensity and short duration of physical activity (PA). However, CLC has not been tested during extended vigorous outdoor exercise common among adolescents. RESEARCH DESIGN AND METHODS Skiing presents unique metabolic challenges: intense prolonged PA, cold, altitude, and stress/fear/excitement. In a randomized controlled trial, 32 adolescents with T1D (ages 10–16 years) participated in a 5-day ski camp (∼5 h skiing/day) at two sites: Wintergreen, VA and Breckenridge, CO. Participants were randomized to the University of Virginia (UVa)–CLC system or remotely monitored sensor-augmented pump (RM-SAP). The CLC and RM-SAP groups were coarsely paired by age and hemoglobin A1c (HbA1c). All subjects were remotely monitored 24 h per day by study physicians and clinical team. RESULTS Compared with physician-monitored open loop, percent time in range (70–180 mg/dL) improved using CLC: 71.3 vs. 64.7% (+6.6% [95% CI 1–12]; P = 0.005), with maximum effect late at night. Hypoglycemia exposure and carbohydrate treatments were improved overall (P = 0.001 and P = 0.007) and during the daytime with strong ski level effects (P = 0.0001 and P = 0.006); ski/snowboard proficiency was balanced between groups but with a very strong site effect: naïve in Virginia and experienced in Colorado. There were no adverse events associated with CLC; the participants’ feedback was overwhelmingly positive. CONCLUSIONS CLC in adolescents with T1D improved glycemic control and reduced exposure to hypoglycemia during prolonged intensive winter sport activities, despite the added challenges of cold and altitude.

    更新日期:2017-09-08
  • Identification of Novel Circulating Biomarkers Predicting Rapid Decline in Renal Function in Type 2 Diabetes: The Fremantle Diabetes Study Phase II
    Diabetes Care (IF 11.857) Pub Date : 2017-08-25
    Kirsten E. Peters; Wendy A. Davis; Jun Ito; Kaye Winfield; Thomas Stoll; Scott D. Bringans; Richard J. Lipscombe; Timothy M.E. Davis

    OBJECTIVE To assess the ability of plasma apolipoprotein (apo) A-IV (apoA4), apo C-III, CD5 antigen-like (CD5L), complement C1q subcomponent subunit B (C1QB), complement factor H–related protein 2, and insulin-like growth factor binding protein 3 (IBP3) to predict rapid decline in estimated glomerular filtration rate (eGFR) in type 2 diabetes. RESEARCH DESIGN AND METHODS Mass spectrometry was used to measure baseline biomarkers in 345 community-based patients (mean age 67.0 years, 51.9% males) from the Fremantle Diabetes Study Phase II. Multiple logistic regression was used to determine clinical predictors of rapid eGFR decline trajectory defined by semiparametric group-based modeling over a 4-year follow-up period. The incremental benefit of each biomarker was then assessed. Similar analyses were performed for a ≥30% eGFR fall, incident chronic kidney disease (eGFR <60 mL/min/1.73 m2), and eGFR decline of ≥5 mL/min/1.73 m2/year. RESULTS Based on eGFR trajectory analysis, 35 participants (10.1%) were defined as “rapid decliners” (mean decrease 2.9 mL/min/1.73 m2/year). After adjustment for clinical predictors, apoA4, CD5L, and C1QB independently predicted rapid decline (odds ratio 2.40 [95% CI 1.24–4.61], 0.52 [0.29–0.93], and 2.41 [1.14–5.11], respectively) and improved model performance and fit (P < 0.001), discrimination (area under the curve 0.75–0.82, P = 0.039), and reclassification (net reclassification index 0.76 [0.63–0.89]; integrated discrimination improvement 6.3% [2.1–10.4%]). These biomarkers and IBP3 contributed to improved model performance in predicting other indices of rapid eGFR decline. CONCLUSIONS The current study has identified novel plasma biomarkers (apoA4, CD5L, C1QB, and IBP3) that may improve the prediction of rapid decline in renal function independently of recognized clinical risk factors in type 2 diabetes.

    更新日期:2017-09-08
  • Pioglitazone Improves Left Ventricular Diastolic Function in Subjects With Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-08-28
    Geoffrey D. Clarke; Carolina Solis-Herrera; Marjorie Molina-Wilkins; Sandra Martinez; Aurora Merovci; Eugenio Cersosimo; Robert J. Chilton; Patricia Iozzo; Amalia Gastaldelli; Muhammad Abdul-Ghani; Ralph A. DeFronzo

    OBJECTIVE To examine the effect of pioglitazone on myocardial insulin sensitivity and left ventricular (LV) function in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Twelve subjects with T2D and 12 with normal glucose tolerance received a euglycemic insulin clamp. Myocardial glucose uptake (MGU) and myocardial perfusion were measured with [18F]fluoro-2-deoxy-d-glucose and [15O]H2O positron emission tomography before and after 24 weeks of pioglitazone treatment. Myocardial function and transmitral early diastolic relation/atrial contraction (E/A) flow ratio were measured with magnetic resonance imaging. RESULTS Pioglitazone reduced HbA1c by 0.9%; decreased systolic and diastolic blood pressure by 7 ± 2 and 7 ± 2 mmHg, respectively (P < 0.05); and increased whole-body insulin-stimulated glucose uptake by 71% (3.4 ± 1.3 to 5.8 ± 2.1 mg/kg · min; P < 0.01) in subjects with T2D. Pioglitazone enhanced MGU by 75% (0.24 ± 0.14 to 0.42 ± 0.13 μmol/min · g; P < 0.01) and myocardial perfusion by 16% (0.95 ± 0.16 to 1.10 ± 0.25 mL/min · g; P < 0.05). Measures of diastolic function, E/A ratio (1.04 ± 0.3 to 1.25 ± 0.4) and peak LV filling rate (349 ± 107 to 433 ± 99 mL/min), both increased (P < 0.01). End-systolic volume, end-diastolic volume, peak LV ejection rate, and cardiac output trended to increase (P not significant), whereas the ejection fraction (61 ± 6 to 66 ± 7%) and stroke volume increased significantly (71 ± 20 to 80 ± 20 L/min; both P < 0.05). CONCLUSIONS Pioglitazone improves whole-body and myocardial insulin sensitivity, LV diastolic function, and systolic function in T2D. Improved myocardial insulin sensitivity and diastolic function are strongly correlated.

    更新日期:2017-09-08
  • The Role of Hyperglycemia, Insulin Resistance, and Blood Pressure in Diabetes-Associated Differences in Cognitive Performance—The Maastricht Study
    Diabetes Care (IF 11.857) Pub Date : 2017-08-24
    Stefan L.C. Geijselaers; Simone J.S. Sep; Danny Claessens; Miranda T. Schram; Martin P.J. van Boxtel; Ronald M.A. Henry; Frans R.J. Verhey; Abraham A. Kroon; Pieter C. Dagnelie; Casper G. Schalkwijk; Carla J.H. van der Kallen; Geert Jan Biessels; Coen D.A. Stehouwer

    OBJECTIVE To study to what extent differences in cognitive performance between individuals with different glucose metabolism status are potentially attributable to hyperglycemia, insulin resistance, and blood pressure–related variables. RESEARCH DESIGN AND METHODS We used cross-sectional data from 2,531 participants from The Maastricht Study (mean age ± SD, 60 ± 8 years; 52% men; n = 666 with type 2 diabetes), all of whom completed a neuropsychological test battery. Hyperglycemia was assessed by a composite index of fasting glucose, postload glucose, glycated hemoglobin (HbA1c), and tissue advanced glycation end products; insulin resistance by the HOMA of insulin resistance index; and blood pressure–related variables included 24-h ambulatory pressures, their weighted SDs, and the use of antihypertensive medication. Linear regression analyses were used to estimate mediating effects. RESULTS After adjustment for age, sex, and education, individuals with type 2 diabetes, compared with those with normal glucose metabolism, performed worse in all cognitive domains (mean differences in composite z scores for memory −0.087, processing speed −0.196, executive function and attention −0.182; P values <0.032), whereas individuals with prediabetes did not. Diabetes-associated differences in processing speed and executive function and attention were largely explained by hyperglycemia (mediating effect 79.6% [bootstrapped 95% CI 36.6; 123.4%] and 50.3% [0.6; 101.2%], respectively) and, for processing speed, to a lesser extent by blood pressure–related variables (17.7% [5.6; 30.1%]), but not by insulin resistance. None of the factors explained the differences in memory function. CONCLUSIONS Our cross-sectional data suggest that early glycemic and blood pressure control, perhaps even in the prediabetic stage, may be promising therapeutic targets for the prevention of diabetes-associated decrements in cognitive performance.

    更新日期:2017-09-08
  • What End Users and Stakeholders Want From Automated Insulin Delivery Systems
    Diabetes Care (IF 11.857) Pub Date : 2017-08-25
    Diana Naranjo; Sakinah C. Suttiratana; Esti Iturralde; Katharine D. Barnard; Jill Weissberg-Benchell; Lori Laffel; Korey K. Hood

    OBJECTIVE The purpose of this study was to rigorously explore psychosocial factors associated with automated insulin delivery systems among people living with type 1 diabetes. RESEARCH DESIGN AND METHODS Across four sites in the U.S. and U.K., 284 participants completed structured interviews or focus groups on expectations, desired features, potential benefits, and perceived burdens of automated insulin delivery systems. Recorded audio files were transcribed and analyzed using NVivo. RESULTS Three themes were identified as critical for uptake of automated insulin delivery: considerations of trust and control, system features, and concerns and barriers to adoption. Children and adolescents with type 1 diabetes primarily identified needs specific to their life stage and social contexts (e.g., school). Adults with type 1 diabetes, parents of youth with type 1 diabetes, and partners of adults with type 1 diabetes were most concerned about the accuracy, adaptability, and algorithm quality alongside expectations that systems stabilize glucose levels and reduce risk for long-term complications. CONCLUSIONS Incorporating stakeholder perspectives on use of automated insulin delivery systems will improve the adoption of devices, quality of life, and likelihood of optimal health. Efforts to build trust in systems, optimize user-system interactions, and provide clear guidance about device capabilities and limitations may help potential users achieve optimal glycemic outcomes.

    更新日期:2017-09-08
  • Influences of Breakfast on Clock Gene Expression and Postprandial Glycemia in Healthy Individuals and Individuals With Diabetes: A Randomized Clinical Trial
    Diabetes Care (IF 11.857) Pub Date : 2017-08-21
    Daniela Jakubowicz; Julio Wainstein; Zohar Landau; Itamar Raz; Bo Ahren; Nava Chapnik; Tali Ganz; Miriam Menaged; Maayan Barnea; Yosefa Bar-Dayan; Oren Froy

    OBJECTIVE The circadian clock regulates glucose metabolism by mediating the activity of metabolic enzymes, hormones, and transport systems. Breakfast skipping and night eating have been associated with high HbA1c and postprandial hyperglycemia after lunch and dinner. Our aim was to explore the acute effect of breakfast consumption or omission on glucose homeostasis and clock gene expression in healthy individuals and individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS In a cross-over design, 18 healthy volunteers and 18 volunteers with 14.5 ± 1.5 years diabetes, BMI 30.7 ± 1.1 kg/m2, and HbA1c 7.6 ± 0.1% (59.6 ± 0.8 mmol/mol) were randomly assigned to a test day with breakfast and lunch (YesB) and a test day with only lunch (NoB). Postprandial clock and clock-controlled gene expression, plasma glucose, insulin, intact glucagon-like peptide-1 (iGLP-1), and dipeptidyl peptidase IV (DPP-IV) plasma activity were assessed after breakfast and lunch. RESULTS In healthy individuals, the expression level of Per1, Cry1, Rorα, and Sirt1 was lower (P < 0.05) but Clock was higher (P < 0.05) after breakfast. In contrast, in individuals with type 2 diabetes, Per1, Per2, and Sirt1 only slightly, but significantly, decreased and Rorα increased (P < 0.05) after breakfast. In healthy individuals, the expression level of Bmal1, Rorα, and Sirt1 was higher (P < 0.05) after lunch on YesB day, whereas the other clock genes remained unchanged. In individuals with type 2 diabetes, Bmal1, Per1, Per2, Rev-erbα, and Ampk increased (P < 0.05) after lunch on the YesB day. Omission of breakfast altered clock and metabolic gene expression in both healthy and individuals with type 2 diabetes. CONCLUSIONS Breakfast consumption acutely affects clock and clock-controlled gene expression leading to normal oscillation. Breakfast skipping adversely affects clock and clock-controlled gene expression and is correlated with increased postprandial glycemic response in both healthy individuals and individuals with diabetes.

    更新日期:2017-09-08
  • Acute Kidney Injury in Patients on SGLT2 Inhibitors: A Propensity-Matched Analysis
    Diabetes Care (IF 11.857) Pub Date : 2017-08-21
    Girish N. Nadkarni; Rocco Ferrandino; Alexander Chang; Aditya Surapaneni; Kinsuk Chauhan; Priti Poojary; Aparna Saha; Bart Ferket; Morgan E. Grams; Steven G. Coca

    OBJECTIVE Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new medications that improve cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). However, the Food and Drug Administration has issued alerts regarding increased acute kidney injury (AKI) risk with canagliflozin and dapagliflozin. We aimed to assess the real-world risk of AKI in new SGLT2 inhibitor users in two large health care utilization cohorts of patients with T2D. RESEARCH DESIGN AND METHODS We used longitudinal data from the Mount Sinai chronic kidney disease registry and the Geisinger Health System cohort. We selected SGLT inhibitor users and nonusers (patients with T2D without SGLT2 inhibitor prescription). We determined AKI by the KDIGO definition (AKIKDIGO). We performed 1:1 nearest-neighbor propensity matching and calculated unadjusted hazard ratios (HRs) and adjusted HRs (aHRs; accounting for covariates poorly balanced) for AKI in primary and sensitivity analyses. RESULTS We identified 377 SGLT2 inhibitor users and 377 nonusers in the Mount Sinai cohort, of whom 3.8 and 9.7%, respectively, had an AKIKDIGO event over a median follow-up time of 14 months. The unadjusted hazards of AKIKDIGO were 60% lower in users (HR 0.4 [95% CI 0.2–0.7]; P = 0.01), which was unchanged (aHR 0.4 [95% CI 0.2–0.7]; P = 0.004) postadjustment. Similarly, we identified 1,207 SGLT2 inhibitor users and 1,207 nonusers in the Geisinger cohort, of whom 2.2 and 4.6% had an AKIKDIGO event. AKIKDIGO unadjusted hazards were lower in users (HR 0.5 [95% CI 0.3–0.8]; P < 0.01) with modest attenuation postadjustment for covariates (aHR 0.6 [95% CI 0.4–1.1]; P = 0.09). These estimates did not qualitatively change across several sensitivity analyses. CONCLUSIONS Our findings do not suggest an increased risk of AKI associated with SGLT2 inhibitor use in patients with T2D in two large health systems.

    更新日期:2017-09-08
  • Association Between Adherence to Pharmacotherapy and Outcomes in Type 2 Diabetes: A Meta-analysis
    Diabetes Care (IF 11.857) Pub Date : 2017-08-18
    Kamlesh Khunti; Samuel Seidu; Setor Kunutsor; Melanie Davies

    OBJECTIVE A previous study suggests an association between poor medication adherence and excess mortality in chronic disease. The purpose of this study was to assess the association between medication adherence and risk of cardiovascular disease (CVD), all-cause mortality, and hospitalization in type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted an electronic search on many electronic databases from inception to 27 April 2016. We selected randomized controlled trials and case-control and cohort studies reporting on CVD, all-cause mortality, or hospitalization outcomes by adherence in adults with type 2 diabetes. Two reviewers independently screened for eligible studies and extracted outcome data. Pooled relative risks (RRs) were calculated using a random-effects meta-analysis; risk of bias in each of the included studies was assessed using the GRADE approach. RESULTS Eight observational studies were included (n = 318,125). The mean rate of poor adherence was 37.8% (95% CI 37.6–38.0). Adjusted estimates were provided by five studies only. The RRs of good (≥80%) versus poor adherence to medication were 0.72 (95% CI 0.62–0.82, I2 = 0%, three studies) for all-cause mortality and 0.90 (0.87–0.94, I2 = 63%, seven studies) for hospitalization. No evidence of small study bias was observed. Only one study reported CVD outcomes by adherence. CONCLUSIONS We identified no trials reporting on outcomes by adherence, suggesting a systematic failure to include this information. Pooled estimates from available observational studies suggest that good medication adherence is associated with reduced risk of all-cause mortality and hospitalization in people with type 2 diabetes, although bias cannot be excluded as an explanation for these findings.

    更新日期:2017-09-08
  • Effect of a Behavioral Intervention Strategy for Adoption and Maintenance of a Physically Active Lifestyle: The Italian Diabetes and Exercise Study (IDES) 2
    Diabetes Care (IF 11.857) Pub Date : 2017-08-18
    Stefano Balducci; Valeria D’Errico; Jonida Haxhi; Massimo Sacchetti; Giorgio Orlando; Patrizia Cardelli; Martina Vitale; Lucilla Bollanti; Francesco Conti; Silvano Zanuso; Antonio Nicolucci; Giuseppe Pugliese; for the Italian Diabetes and Exercise Study 2 (IDES­_2) Investigators

    OBJECTIVE Adherence to physical activity (PA) recommendations is hampered by the lack of effective strategies to promote behavior change. The Italian Diabetes and Exercise Study_2 is a randomized controlled trial evaluating a novel behavioral intervention strategy for increasing PA and decreasing sedentary time (SED-time) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS The study randomized 300 physically inactive and sedentary patients with type 2 diabetes 1:1 to receive theoretical and practical counseling once yearly for 3 years (intervention group [INT]) or standard care (control group [CON]). Here, we report the 4-month effects on objectively (accelerometer) measured daily light-intensity PA (LPA), moderate-to-vigorous–intensity PA (MVPA), and SED-time, and cardiovascular risk factors. RESULTS LPA and MVPA both increased, and SED-time decreased in both groups, although changes were significantly more marked in INT participants (approximately twofold for LPA and SED-time and approximately sixfold for MVPA). A significant reduction in HbA1c was observed only in INT subjects. An increase in LPA >0.92 h · day−1 and in MVPA >7.33 min · day−1 and a decrease in SED-time >1.05 h · day−1 were associated with a average decrease in HbA1c of ∼1% and also with significant improvements in fasting glucose, body weight, waist circumference, and hs-CRP. Changes in PA and SED-time were independent predictors of improvements in HbA1c. CONCLUSIONS This behavioral intervention is effective in the short-term for increasing LPA and MVPA and reducing SED-time. Significant improvements in cardiometabolic risk profiles were observed in subjects experiencing the most pronounced changes in PA and SED-time, even if below the recommended level.

    更新日期:2017-09-08
  • Efficacy and Safety of Diacerein in Patients With Inadequately Controlled Type 2 Diabetes: A Randomized Controlled Trial
    Diabetes Care (IF 11.857) Pub Date : 2017-08-17
    Claudia R.L. Cardoso; Nathalie C. Leite; Fernanda O. Carlos; Andréia A. Loureiro; Bianca B. Viegas; Gil F. Salles

    OBJECTIVE To assess, in a randomized, double-blind, and placebo-controlled trial, the efficacy and safety of diacerein, an immune modulator anti-inflammatory drug, in improving glycemic control of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Eighty-four patients with HbA1c between 7.5 and 9.5% (58–80 mmol/mol) were randomized to 48-week treatment with placebo (n = 41) or diacerein 100 mg/day (n = 43). The primary outcome was the difference in mean HbA1c changes during treatment. Secondary outcomes were other efficacy and safety measurements. A general linear regression with repeated measures, adjusted for age, sex, diabetes duration, and each baseline value, was used to estimate differences in mean changes. Both intention-to-treat (ITT) analysis and per-protocol analysis (excluding 10 patients who interrupted treatment) were performed. RESULTS Diacerein reduced HbA1c compared with placebo by 0.35% (3.8 mmol/mol; P = 0.038) in the ITT analysis and by 0.41% (4.5 mmol/mol; P = 0.023) in the per-protocol analysis. The peak of effect occurred at the 24th week of treatment (−0.61% [6.7 mmol/mol; P = 0.014] and −0.78% [8.5 mmol/mol; P = 0.005], respectively), but it attenuated toward nonsignificant differences at the 48th week. No significant effect of diacerein was observed in other efficacy and safety measures. Diarrhea occurred in 65% of patients receiving diacerein and caused treatment interruption in 16%. Seven patients in the diacerein group reduced insulin dosage, whereas 10 in the placebo group increased it; however, mild hypoglycemic events were equally observed. CONCLUSIONS Diacerein reduced mean HbA1c levels, with peak of effect at the 24th week of treatment. The drug was well tolerated and may be indicated as adjunct treatment in patients with type 2 diabetes, particularly in those with osteoarthritis.

    更新日期:2017-09-08
  • Prognosis and Its Predictors After Incident Stroke in Patients With Type 1 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-08-10
    Stefanie Hägg-Holmberg; Lena M Thorn; Carol M Forsblom; Daniel Gordin; Nina Elonen; Valma Harjutsalo; Ron Liebkind; Jukka Putaala; Turgut Tatlisumak; Per-Henrik Groop; on behalf of the FinnDiane Study Group

    OBJECTIVE Although patients with type 1 diabetes have a poor prognosis after a stroke, predictors of survival after an incident stroke in these patients are poorly studied. RESEARCH DESIGN AND METHODS In this observational study, a total of 144 patients of 4,083 with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study suffered an incident stroke in 1997–2010, and were followed for a mean 3.4 ± 3.1 years after the stroke. Information was recorded on hard cardiovascular events and death as a result of cardiovascular or diabetes-related cause, collectively referred to as vascular composite end point. Information was collected from medical records, death certificates, and the National Care Register of Health Care. Predictors at the time of the incident stroke were studied for the end points. RESULTS During follow-up, 104 (72%) patients suffered a vascular composite end point. Of these, 33 (32%) had a recurrent stroke, 33 (32%) a hard cardiovascular event, and 76 (53%) died of cardiovascular or diabetes-related causes, with an overall 1-year survival of 76% and 5-year survival of 58%. The predictors of a vascular composite end point were hemorrhagic stroke subtype (hazard ratio 2.03 [95% CI 1.29–3.19]), as well as chronic kidney disease stage 2 (2.48 [1.17–5.24]), stage 3 (3.04 [1.54–6.04]), stage 4 (3.95 [1.72–9.04]), and stage 5 (6.71 [3.14–14.34]). All-cause mortality increased with deteriorating kidney function. CONCLUSIONS Patients with type 1 diabetes with an incident stroke have a poor cardiovascular prognosis and a high risk of all-cause mortality. In particular, hemorrhagic stroke subtype and progression of diabetic kidney disease conveys worse outcome.

    更新日期:2017-09-08
  • Can Secure Patient-Provider Messaging Improve Diabetes Care?
    Diabetes Care (IF 11.857) Pub Date : 2017-08-10
    Sukyung Chung; Laura Panattoni; Jeffrey Chi; Latha Palaniappan

    OBJECTIVE Internet-based secure messaging between patients and providers through a patient portal is now common in the practice of modern medicine. There is limited evidence on how messaging is associated with use and clinical quality measures among patients with type 2 diabetes. We examine whether messaging with physicians for medical advice is associated with fewer face-to-face visits and better diabetes management. RESEARCH DESIGN AND METHODS Patients with diabetes who were enrolled in an online portal of an outpatient health care organization in 2011–2014 were studied (N = 37,762 patient-years). Messages from/to primary care physicians or diabetes-related specialists for medical advice were considered. We estimated the association of messaging with diabetes quality measures, adjusting for patient and provider characteristics and patient-level clustering. RESULTS Most patients (72%) used messaging, and those who made frequent visits were also more likely to message. Given visit frequency, no (vs. any) messaging was negatively associated with the likelihood of meeting an HbA1c target of <8% (64 mmol/mol) (odds ratio [OR] 0.83 [95% CI 0.77, 0.90]). Among message users, additional messages (vs. 1) were associated with better outcome (two more messages: OR 1.17 [95% CI 1.06, 1.28]; three more messages: 1.38 [1.25, 1.53]; four more messages: 1.55 [1.43, 1.69]). The relationship was stronger for noninsulin users. Message frequency was also positively associated, but to a smaller extent, with process measures (e.g., eye examination). Physician-initiated messages had effects similar to those for patient-initiated messages. CONCLUSIONS Patients with diabetes frequently used secure messaging for medical advice in addition to routine visits to care providers. Messaging was positively associated with better diabetes management in a large community outpatient practice.

    更新日期:2017-09-08
  • Type 2 Diabetes in the Real World: The Elusive Nature of Glycemic Control
    Diabetes Care (IF 11.857) Pub Date : 2017-08-10
    Steven V. Edelman; William H. Polonsky

    Despite U.S. Food and Drug Administration (FDA) approval of over 40 new treatment options for type 2 diabetes since 2005, the latest data from the National Health and Nutrition Examination Survey show that the proportion of patients achieving glycated hemoglobin (HbA1c) <7.0% (<53 mmol/mol) remains around 50%, with a negligible decline between the periods 2003–2006 and 2011–2014. The Healthcare Effectiveness Data and Information Set reports even more alarming rates, with only about 40% and 30% of patients achieving HbA1c <7.0% (<53 mmol/mol) in the commercially insured (HMO) and Medicaid populations, respectively, again with virtually no change over the past decade. A recent retrospective cohort study using a large U.S. claims database explored why clinical outcomes are not keeping pace with the availability of new treatment options. The study found that HbA1c reductions fell far short of those reported in randomized clinical trials (RCTs), with poor medication adherence emerging as the key driver behind the disconnect. In this Perspective, we examine the implications of these findings in conjunction with other data to highlight the discrepancy between RCT findings and the real world, all pointing toward the underrealized promise of FDA-approved therapies and the critical importance of medication adherence. While poor medication adherence is not a new issue, it has yet to be effectively addressed in clinical practice—often, we suspect, because it goes unrecognized. To support the busy health care professional, innovative approaches are sorely needed.

    更新日期:2017-09-08
  • Understanding the Gap Between Efficacy in Randomized Controlled Trials and Effectiveness in Real-World Use of GLP-1RA and DPP4 Therapies in Patients With Type 2 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-08-10
    Ginger S. Carls; Edward Tuttle; Ruo-Ding Tan; Johnny Huynh; John Yee; Steven V. Edelman; William H. Polonsky

    OBJECTIVE This objective of this study was to estimate and explain the gap between clinical efficacy and real-world (RW) effectiveness of type 2 diabetes medications. RESEARCH DESIGN AND METHODS This mixed-methods quasi-experimental study used retrospective claims (Optum/Humedica) to compare the change in HbA1c of RW patients with type 2 diabetes 12 months after starting a glucagon-like peptide-1 receptor agonist (GLP-1RA) or dipeptidyl peptidase-4 inhibitor (DPP4) with published findings from randomized controlled trials (RCTs) evaluating these drugs. Selected RW patients were similar to RCT patients, and regression analysis was used in the RW data to adjust for differences between poorly adherent and adherent patients to explain why RCT and RW findings may differ. RESULTS RW patients initiating a GLP-1RA (n = 221) or a DPP4 (n = 652) experienced smaller reductions in HbA1c (GLP-1RA: −0.52% [−6 mmol/mol], DPP4: −0.51% [−6 mmol/mol])than reported in RCTs (−1.30% [−14 mmol/mol] from seven GLP-1RA RCTs, n = 2,600; −0.68% [−8 mmol/mol] from four DPP4 RCTs, n = 1,889). Baseline HbA1c, additional medications, and adherence were significant explanatory factors in the RW HbA1c change. Modeled estimates of RCT efficacy (−1.04% GLP-1RA [−12 mmol/mol], −0.69% DPP4 [−8 mmol/mol]) were within the RCTs’ reported range (GLP-1RA: −0.84% to −1.60% [−9 to −18 mmol/mol]; DPP4: −0.47% to −0.90% [−5 to −10 mmol/mol]). Poor medication adherence accounted for approximately three-fourths of the gap between RW and expected RCT results (gap = 0.51% [6 mmol/mol] GLP1-RA; 0.18% [3 mmol/mol] DPP4). CONCLUSIONS Poor medication adherence is primarily why RW effectiveness is significantly less than RCT efficacy, suggesting an urgent need to effectively address adherence among patients with type 2 diabetes.

    更新日期:2017-09-08
  • The Association of Falling Insulin Requirements With Maternal Biomarkers and Placental Dysfunction: A Prospective Study of Women With Pre-existing Diabetes in Pregnancy
    Diabetes Care (IF 11.857) Pub Date : 2017-08-09
    Suja Padmanabhan; Vincent W. Lee; Mark Mclean; Neil Athayde; Valeria Lanzarone; Qemer Khoshnow; Michael J. Peek; N. Wah Cheung

    OBJECTIVE To investigate the association of falling insulin requirements (FIR) among women with pre-existing diabetes with adverse obstetric outcomes and maternal biomarkers longitudinally in pregnancy. RESEARCH DESIGN AND METHODS A multicenter prospective cohort study of 158 women (41 with type 1 diabetes and 117 with type 2 diabetes) was conducted. Women with FIR of ≥15% from the peak total daily dose after 20 weeks gestation were considered case subjects (n = 32). The primary outcome was a composite of clinical markers of placental dysfunction (pre-eclampsia, small for gestational age [≤5th centile], stillbirth, premature delivery [<30 weeks], and placental abruption). Maternal circulating angiogenic markers (placental growth factor [PlGF] and soluble fms-like tyrosine kinase 1 [sFlt-1]), placental hormones (human placental lactogen, progesterone, and tumor necrosis factor-α), HbA1c, and creatinine were studied serially during pregnancy. RESULTS FIR ≥15% was associated with an increased risk of the composite primary outcome (odds ratio [OR] 4.38 [95% CI 1.9–10.3]; P < 0.001), pre-eclampsia (OR 6.76 [95% CI 2.7–16.7]; P < 0.001), and was more common among women with type 1 diabetes (36.6 vs. 14.5%; P = 0.002). Creatinine was modestly elevated among women with FIR ≥15%; however, there was no difference in HbA1c. The ratio of sFlt-1 to PlGF was significantly higher among women with FIR at 25, 30, and 36 weeks, with differences maintained in the subgroup that developed pre-eclampsia. There was no difference in placental hormones between the groups. CONCLUSIONS This is the first prospective study to associate FIR with altered expression of placental antiangiogenic factors and pre-eclampsia. FIR is an important clinical sign, among women with pre-existing diabetes, that should alert the clinician to investigate underlying placental dysfunction.

    更新日期:2017-09-08
  • The Changing Tides of the Type 2 Diabetes Epidemic—Smooth Sailing or Troubled Waters Ahead? Kelly West Award Lecture 2016
    Diabetes Care (IF 11.857) Pub Date : 2017-08-04
    Edward W. Gregg

    The Kelly West Award for Outstanding Achievement in Epidemiology is given in memory of Kelly M. West, widely regarded as the “father of diabetes epidemiology,” to an individual who has made significant contributions to the field of diabetes epidemiology. Edward W. Gregg, PhD, of the Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA, received the prestigious award at the American Diabetes Association's 76th Scientific Sessions, 10–14 June 2016, in New Orleans, LA. He presented the Kelly West Award Lecture, “Changing Tides of the Type 2 Diabetes Epidemic—Smooth Sailing or Troubled Waters Ahead?” on Sunday, 12 June 2016.

    更新日期:2017-09-08
  • Effect of Intensive Versus Standard Blood Pressure Treatment According to Baseline Prediabetes Status: A Post Hoc Analysis of a Randomized Trial
    Diabetes Care (IF 11.857) Pub Date : 2017-08-08
    Adam P. Bress; Jordan B. King; Kathryn E. Kreider; Srinivasan Beddhu; Debra L. Simmons; Alfred K. Cheung; Yingying Zhang; Michael Doumas; John Nord; Mary Ellen Sweeney; Addison A. Taylor; Charles Herring; William J. Kostis; James Powell; Anjay Rastogi; Christianne L. Roumie; Alan Wiggers; Jonathan S. Williams; Reem Yunis; Athena Zias; Greg W. Evans; Tom Greene; Michael V. Rocco; William C. Cushman; David M. Reboussin; Mark N. Feinglos; Vasilios Papademetriou; for the SPRINT Research Group

    OBJECTIVE To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with prediabetes versus those with fasting normoglycemia at baseline in the Systolic Blood Pressure Intervention Trial (SPRINT). RESEARCH DESIGN AND METHODS This was a post hoc analysis of SPRINT. SPRINT participants were categorized by prediabetes status, defined as baseline fasting serum glucose ≥100 mg/dL versus those with normoglycemia (fasting serum glucose <100 mg/dL). The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment among those with prediabetes and normoglycemia. RESULTS Among 9,361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 3,898 and 5,425 had baseline prediabetes and normoglycemia, respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.69 (95% CI 0.53, 0.89) and 0.83 (95% CI 0.66, 1.03) among those with prediabetes and normoglycemia, respectively (P value for interaction 0.30). For all-cause mortality, the hazard ratio with intensive SBP treatment was 0.77 (95% CI 0.55, 1.06) for prediabetes and 0.71 (95% CI 0.54, 0.94) for normoglycemia (P value for interaction 0.74). Effects of intensive versus standard SBP treatment on prespecified renal outcomes and serious adverse events were similar for prediabetes and normoglycemia (all interaction P > 0.05). CONCLUSIONS In SPRINT, the beneficial effects of intensive SBP treatment were similar among those with prediabetes and fasting normoglycemia.

    更新日期:2017-09-08
  • Arteriolar Hyalinosis Predicts Increase in Albuminuria and GFR Decline in Normo- and Microalbuminuric Japanese Patients With Type 2 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-08-03
    Tatsumi Moriya; Kazuki Omura; Madoka Matsubara; Yuki Yoshida; Kei Hayama; Motoshi Ouchi

    OBJECTIVE This study investigated the association between renal histology, as assessed by morphometric analysis using light (LM) and electron (EM) microscopy, and changes in urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in Japanese people with type 2 diabetes in the early stages of diabetic nephropathy. RESEARCH DESIGN AND METHODS We performed percutaneous renal biopsies in 29 patients with type 2 diabetes (22 men, mean ± SD age 49 ± 10 years and GFR 119 ± 27 mL/min/1.73 m2, with 15 normoalbuminuric [UAE <20 μg/min], and 14 microalbuminuric [UAE 20–200 μg/min]) to clarify which histological factors were associated with changes in UAE and GFR during 8.0 ± 3.5 years’ follow-up. Glomerular structural changes including mesangial volume fraction [Vv(Mes/glom)] were estimated using EM, whereas the index of arteriolar hyalinosis (IAH) score was assessed by LM. Patients underwent annual measurement of GFR using iohexol injection with simultaneous urine collections for UAE. RESULTS Vv(Mes/glom) was negatively correlated with baseline and follow-up GFR but not with UAE. The IAH score was positively correlated with UAE and negatively correlated with GFR at follow-up, but it was not correlated with either UAE or GFR at baseline. GFR at follow-up was significantly decreased from baseline in patients with IAH scores ≥2.0 and significantly lower than in patients with IAH scores <2.0. Patients with IAH scores <2.0 showed no significant change in GFR during follow-up. CONCLUSIONS Arteriolar hyalinosis is an additional histological predictor for albuminuria increase and GFR decline in normo- and microalbuminuric Japanese people with type 2 diabetes.

    更新日期:2017-09-08
  • All-Cause and Specific-Cause Mortality Risk After Roux-en-Y Gastric Bypass in Patients With and Without Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-07-27
    Michelle R. Lent; Peter N. Benotti; Tooraj Mirshahi; Glenn S. Gerhard; William E. Strodel; Anthony T. Petrick; Jon D. Gabrielsen; David D. Rolston; Christopher D. Still; Annemarie G. Hirsch; Fahad Zubair; Adam Cook; David J. Carey; G. Craig Wood

    OBJECTIVE This study assessed all-cause and specific-cause mortality after Roux-en-Y gastric bypass (RYGB) and in matched control subjects, stratified by diabetes status. RESEARCH DESIGN AND METHODS RYGB patients were matched by age, BMI, sex, and diabetes status at time of surgery to nonsurgical control subjects using data from the electronic health record. Kaplan-Meier curves and Cox regression were used to assess differences in all-cause and specific-cause mortality between RYGB patients and control subjects with and without diabetes. RESULTS Of the 3,242 eligible RYGB patients enrolled from January 2004 to December 2015, control subjects were identified for 2,428 (n = 625 with diabetes and n = 1,803 without diabetes). Median postoperative follow-up was 5.8 years for patients with diabetes and 6.7 years for patients without diabetes. All-cause mortality was reduced in RYGB patients compared with control subjects only for those with diabetes at the time of surgery (adjusted hazard ratio = 0.44; P < 0.0001). Mortality was not significantly improved in RYGB patients without diabetes compared with control subjects without diabetes (adjusted hazard ratio 0.84; P = 0.37). Deaths from cardiovascular diseases (P = 0.011), respiratory conditions (P = 0.017), and diabetes P = 0.011) were more frequent in control subjects with diabetes than in RYGB patients with diabetes. RYGB patients without diabetes were less likely to die of cancer (P = 0.0038) and respiratory diseases (P = 0.046) than control subjects without diabetes, but were at higher risk of death from external causes (P = 0.012), including intentional self-harm (P = 0.025) than control subjects without diabetes. CONCLUSIONS All-cause mortality benefits of RYGB are driven predominantly by patients with diabetes at the time of surgery. RYGB patients with diabetes were less likely to die of cardiovascular diseases, diabetes, and respiratory conditions than their counterparts without RYGB.

    更新日期:2017-09-08
  • Comparison of Ipragliflozin and Pioglitazone Effects on Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Randomized, 24-Week, Open-Label, Active-Controlled Trial
    Diabetes Care (IF 11.857) Pub Date : 2017-07-28
    Daisuke Ito; Satoshi Shimizu; Kazuyuki Inoue; Daigo Saito; Morifumi Yanagisawa; Kouichi Inukai; Yuji Akiyama; Yoshihiro Morimoto; Mitsuhiko Noda; Akira Shimada

    OBJECTIVE To compare the efficacy of ipragliflozin versus pioglitazone in patients with type 2 diabetes complicated by nonalcoholic fatty liver disease (NAFLD). RESEARCH DESIGN AND METHODS In this open-label, randomized, active-controlled trial, we randomly assigned 66 patients with type 2 diabetes and NAFLD to receive ipragliflozin 50 mg (n = 32) or pioglitazone 15–30 mg (n = 34) orally once daily. The primary outcome was a change from baseline in the liver-to-spleen attenuation ratio (L/S ratio) on computed tomography at week 24. RESULTS At week 24, the mean ± SD L/S ratio had increased by 0.22 (from 0.80 ± 0.24 to 1.00 ± 0.18) in the ipragliflozin group and 0.21 (from 0.78 ± 0.26 to 0.98 ± 0.16) in the pioglitazone group (P = 0.90). Serum aspartate and alanine aminotransferase levels, HbA1c, and fasting plasma glucose were similarly reduced in the two treatment groups. Nevertheless, body weight and visceral fat area showed significant reductions only in the ipragliflozin group compared with the pioglitazone group (P < 0.0001 and P = 0.0013, respectively). There were no serious adverse events in either group. CONCLUSIONS Compared with pioglitazone, ipragliflozin exerts equally beneficial effects on NAFLD and glycemic control during the treatment of patients with type 2 diabetes complicated by NAFLD. Furthermore, ipragliflozin significantly reduced body weight and abdominal fat area.

    更新日期:2017-09-08
  • Defects in α-Cell Function in Patients With Diabetes Due to Chronic Pancreatitis Compared With Patients With Type 2 Diabetes and Healthy Individuals
    Diabetes Care (IF 11.857) Pub Date : 2017-07-27
    Lena Mumme; Thomas G.K. Breuer; Stephan Rohrer; Nina Schenker; Björn A. Menge; Jens J. Holst; Michael A. Nauck; Juris J. Meier

    OBJECTIVE Diabetes frequently develops in patients with chronic pancreatitis. We examined the alterations in the glucagon response to hypoglycemia and to oral glucose administration in patients with diabetes due to chronic pancreatitis. RESEARCH DESIGN AND METHODS Ten patients with diabetes secondary to chronic pancreatitis were compared with 13 patients with type 2 diabetes and 10 healthy control subjects. A stepwise hypoglycemic clamp and an oral glucose tolerance test (OGTT) were performed. RESULTS Glucose levels during the OGTT were higher in patients with diabetes and chronic pancreatitis and lower in control subjects (P < 0.0001). Insulin and C-peptide levels were reduced, and the glucose-induced suppression of glucagon was impaired in both groups with diabetes (all P < 0.0001 vs. control subjects). During hypoglycemia, glucagon concentrations were reduced in patients with chronic pancreatitis and with type 2 diabetes (P < 0.05). The increase in glucagon during the clamp was inversely related to the glucose-induced glucagon suppression and positively related to β-cell function. Growth hormone responses to hypoglycemia were lower in patients with type 2 diabetes (P = 0.0002) but not in patients with chronic pancreatitis. CONCLUSIONS α-Cell responses to oral glucose ingestion and to hypoglycemia are disturbed in patients with diabetes and chronic pancreatitis and in patients with type 2 diabetes. The similarities between these defects suggest a common etiology.

    更新日期:2017-09-08
  • A National Effort to Prevent Type 2 Diabetes: Participant-Level Evaluation of CDC’s National Diabetes Prevention Program
    Diabetes Care (IF 11.857) Pub Date : 2017-07-20
    Elizabeth K. Ely; Stephanie M. Gruss; Elizabeth T. Luman; Edward W. Gregg; Mohammed K. Ali; Kunthea Nhim; Deborah B. Rolka; Ann L. Albright

    OBJECTIVE To assess participant-level results from the first 4 years of implementation of the National Diabetes Prevention Program (National DPP), a national effort to prevent type 2 diabetes in those at risk through structured lifestyle change programs. RESEARCH DESIGN AND METHODS Descriptive analysis was performed on data from 14,747 adults enrolled in year-long type 2 diabetes prevention programs during the period February 2012 through January 2016. Data on attendance, weight, and physical activity minutes were summarized and predictors of weight loss were examined using a mixed linear model. All analyses were performed using SAS 9.3. RESULTS Participants attended a median of 14 sessions over an average of 172 days in the program (median 134 days). Overall, 35.5% achieved the 5% weight loss goal (average weight loss 4.2%, median 3.1%). Participants reported a weekly average of 152 min of physical activity (median 128 min), with 41.8% meeting the physical activity goal of 150 min per week. For every additional session attended and every 30 min of activity reported, participants lost 0.3% of body weight (P < 0.0001). CONCLUSIONS During the first 4 years, the National DPP has achieved widespread implementation of the lifestyle change program to prevent type 2 diabetes, with promising early results. Greater duration and intensity of session attendance resulted in a higher percent of body weight loss overall and for subgroups. Focusing on retention may reduce disparities and improve overall program results. Further program expansion and investigation is needed to continue lowering the burden of type 2 diabetes nationally.

    更新日期:2017-09-08
  • Incidence and Trends in Hypoglycemia Hospitalization in Adults With Type 1 and Type 2 Diabetes in England, 1998–2013: A Retrospective Cohort Study
    Diabetes Care (IF 11.857) Pub Date : 2017-07-17
    Victor W. Zhong; Juhaeri Juhaeri; Stephen R. Cole; Evangelos Kontopantelis; Christina M. Shay; Penny Gordon-Larsen; Elizabeth J. Mayer-Davis

    OBJECTIVE To determine trends in hospitalization for hypoglycemia in adults with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in England. RESEARCH DESIGN AND METHODS Adults with T1DM or T2DM were identified from 398 of the 684 practices within the Clinical Practice Research Datalink, for which linkage to the Hospital Episode Statistics was possible. Hypoglycemia as primary reason for hospitalization between 1998 and 2013 was extracted. Trends were estimated using joinpoint regression models for adults with T1DM, young and middle-aged adults with T2DM (18–64 years), and elderly adults with T2DM (≥65 years), respectively. RESULTS Among 23,246 adults with T1DM, 1,591 hypoglycemia hospitalizations occurred during 121,262 person-years. Among 241,441 adults with T2DM, 3,738 hypoglycemia hospitalizations occurred during 1,344,818 person-years. In adults with T1DM, the incidence increased 3.74% (95% CI 1.70–5.83) annually from 1998 to 2013. In young and middle-aged adults with T2DM, the annual incidence increase was 4.12% (0.61–7.75) from 1998 to 2013. In elderly adults with T2DM, the incidence increased 8.59% (5.76–11.50) annually from 1998 to 2009, and decreased 8.05% (−14.48 to −1.13) annually from 2009 to 2013, but the incidence was still higher in 2013 than 1998 (adjusted rate ratio 3.01 [1.76–5.14]). Trends in HbA1c level did not parallel trends of hypoglycemia hospitalization for both diabetes types. A possible reason for declined hypoglycemia trend in 2009–2013 in elderly adults with T2DM may be continuously decreased sulfonylurea use after 2009, which was not seen in young and middle-aged adults with T2DM. CONCLUSIONS Hypoglycemia requiring hospitalization has been an increasing burden in adults with T1DM and T2DM in England in the previous two decades, with the exception of the decline in elderly adults with T2DM starting in 2009.

    更新日期:2017-09-08
  • Dulce Digital: An mHealth SMS-Based Intervention Improves Glycemic Control in Hispanics With Type 2 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-06-02
    Addie L. Fortmann; Linda C. Gallo; Maria Isabel Garcia; Mariam Taleb; Johanna A. Euyoque; Taylor Clark; Jessica Skidmore; Monica Ruiz; Sapna Dharkar-Surber; James Schultz; Athena Philis-Tsimikas

    OBJECTIVE Type 2 diabetes is growing in epidemic proportions and disproportionately affects lower income, diverse communities. Text messaging may provide one of the most rapid methods to overcome the “digital divide” to improve care. RESEARCH DESIGN AND METHODS A randomized, nonblinded, parallel-groups clinical trial design allocated N = 126 low-income, Hispanic participants with poorly controlled type 2 diabetes to receive the Dulce Digital intervention or usual care (UC). Dulce Digital participants received up to three motivational, educational, and/or call-to-action text messages per day over 6 months. The primary outcome was HbA1c; lipids, blood pressure, and BMI were secondary outcomes. Satisfaction and acceptability were evaluated via focus groups and self-report survey items. RESULTS The majority of patients were middle aged (mean age 48.43 years, SD 9.80 years), female (75%), born in Mexico (91%), uninsured (75%), and reported less than a ninth-grade education level (73%); mean baseline HbA1c 9.5% (80 mmol/mol), SD 1.3, and fasting plasma glucose 187.17 mg/dL, SD 64.75. A statistically significant time-by-group interaction effect indicated that the Dulce Digital group achieved a significantly greater reduction in HbA1c over time compared with UC (P = 0.03). No statistically significant effects were observed for secondary clinical indicators. The number of blood glucose values texted in by participants was a statistically significant predictor of month 6 HbA1c (P < 0.05). Satisfaction and acceptability ratings for the Dulce Digital intervention were high. CONCLUSIONS Use of a simple, low-cost text-messaging program was found to be highly acceptable in this sample of high-risk, Hispanic individuals with type 2 diabetes and resulted in greater improvement in glycemic control compared with UC.

    更新日期:2017-09-08
  • Diabetes, Associated Clinical Spectrum, Long-term Prognosis and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1 B (HNF1B) Molecular Defects
    Diabetes Care (IF 11.857) Pub Date : 2017-04-17
    Danièle Dubois-Laforgue; Erika Cornu; Cécile Saint-Martin; Joël Coste; Christine Bellanné-Chantelot; José Timsit; for the Monogenic Diabetes Study Group of the Société Francophone du Diabète

    OBJECTIVE Molecular defects of hepatocyte nuclear factor 1B (HNF1B) are associated with a multiorgan disease, including diabetes (maturity-onset diabetes of the young 5) and kidney abnormalities. The HNF1B-syndrome is related to HNF1B mutations or to a 17q12 deletion spanning 15 genes, including HNF1B. Here, we described HNF1B-related diabetes and associated phenotypes and assessed genotype/phenotype correlations at diagnosis and in the long-term. RESEARCH DESIGN AND METHODS This multicenter retrospective cohort study included 201 patients, aged 18 or older at follow-up, with HNF1B mutations (n = 101) or deletion (n = 100). RESULTS Diabetes was present in 159 patients. At diagnosis, clinical symptoms of diabetes were present in 67 of 144 patients, and HNF1B-renal disease in 64 of 102. Although responsiveness to sulfonylureas/repaglinide was observed in 29 of the 51 tested, 111 of 140 patients (79%) were treated with insulin at follow-up. Diabetic retinopathy and/or neuropathy were present in 46 of 114 patients. Renal cysts were present in 122 of 166 patients, chronic kidney disease (CKD) stages 3–4 in 75 of 169 (44%), and end-stage renal disease (ESRD) in 36 of 169 (21%). Compared with the patients with mutations, those with HNF1B deletion had less often CKD3–4/ESRD at diagnosis (11 of 43 vs. 27 of 35, P < 10−4) and in the long-term (40 of 78 vs. 71 of 91, P = 0.0003). They were leaner and more frequently treated with insulin. CONCLUSIONS In patients with HNF1B-syndrome, diabetes complications, cardiovascular risk factors, CKD3–4, and ESRD are highly prevalent. At diabetes diagnosis, the presence of morphological and/or functional kidney disease may help etiological diagnosis. Genotype/phenotype correlations may have implications for the care and the prognosis of these patients.

    更新日期:2017-09-08
  • National Standards for Diabetes Self-Management Education and Support
    Diabetes Care (IF 11.857) Pub Date : 2012-11-01
    Linda Haas; Melinda Maryniuk; Joni Beck; Carla E. Cox; Paulina Duker; Laura Edwards; Edwin B. Fisher; Lenita Hanson; Daniel Kent; Leslie Kolb; Sue McLaughlin; Eric Orzeck; John D. Piette; Andrew S. Rhinehart; Russell Rothman; Sara Sklaroff; Donna Tomky; Gretchen Youssef; on behalf of the 2012 Standards Revision Task Force

    By the most recent estimates, 18.8 million people in the U.S. have been diagnosed with diabetes and an additional 7 million are believed to be living with undiagnosed diabetes. At the same time, 79 million people are estimated to have blood glucose levels in the range of prediabetes or categories of increased risk for diabetes. Thus, more than 100 million Americans are at risk for developing the devastating complications of diabetes (1).

    更新日期:2017-09-08
  • Economic Costs of Diabetes in the U.S. in 2012
    Diabetes Care (IF 11.857) Pub Date : 2013-04-01
    American Diabetes Association

    OBJECTIVE This study updates previous estimates of the economic burden of diagnosed diabetes and quantifies the increased health resource use and lost productivity associated with diabetes in 2012. RESEARCH DESIGN AND METHODS The study uses a prevalence-based approach that combines the demographics of the U.S. population in 2012 with diabetes prevalence, epidemiological data, health care cost, and economic data into a Cost of Diabetes Model. Health resource use and associated medical costs are analyzed by age, sex, race/ethnicity, insurance coverage, medical condition, and health service category. Data sources include national surveys, Medicare standard analytical files, and one of the largest claims databases for the commercially insured population in the U.S. RESULTS The total estimated cost of diagnosed diabetes in 2012 is $245 billion, including $176 billion in direct medical costs and $69 billion in reduced productivity. The largest components of medical expenditures are hospital inpatient care (43% of the total medical cost), prescription medications to treat the complications of diabetes (18%), antidiabetic agents and diabetes supplies (12%), physician office visits (9%), and nursing/residential facility stays (8%). People with diagnosed diabetes incur average medical expenditures of about $13,700 per year, of which about $7,900 is attributed to diabetes. People with diagnosed diabetes, on average, have medical expenditures approximately 2.3 times higher than what expenditures would be in the absence of diabetes. For the cost categories analyzed, care for people with diagnosed diabetes accounts for more than 1 in 5 health care dollars in the U.S., and more than half of that expenditure is directly attributable to diabetes. Indirect costs include increased absenteeism ($5 billion) and reduced productivity while at work ($20.8 billion) for the employed population, reduced productivity for those not in the labor force ($2.7 billion), inability to work as a result of disease-related disability ($21.6 billion), and lost productive capacity due to early mortality ($18.5 billion). CONCLUSIONS The estimated total economic cost of diagnosed diabetes in 2012 is $245 billion, a 41% increase from our previous estimate of $174 billion (in 2007 dollars). This estimate highlights the substantial burden that diabetes imposes on society. Additional components of societal burden omitted from our study include intangibles from pain and suffering, resources from care provided by nonpaid caregivers, and the burden associated with undiagnosed diabetes.

    更新日期:2017-09-08
  • Long-Acting Glucagon-Like Peptide 1 Receptor Agonists
    Diabetes Care (IF 11.857) Pub Date : 2011-05-01
    Alan J. Garber

    Targeting the incretin system has become an important therapeutic approach for treating type 2 diabetes. Two drug classes have been developed: glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors. Clinical data have revealed that these therapies improve glycemic control while reducing body weight (GLP-1 receptor agonists, specifically) and systolic blood pressure (SBP) in patients with type 2 diabetes. Furthermore, incidence of hypoglycemia is relatively low with these treatments (except when used in combination with a sulfonylurea) because of their glucose-dependent mechanism of action. There are currently two GLP-1 receptor agonists available (exenatide and liraglutide), with several more currently being developed. This review considers the efficacy and safety of both the short- and long-acting GLP-1 receptor agonists. Head-to-head clinical trial data suggest that long-acting GLP-1 receptor agonists produce superior glycemic control when compared with their short-acting counterparts. Furthermore, these long-acting GLP-1 receptor agonists were generally well tolerated, with transient nausea being the most frequently reported adverse effect.

    更新日期:2017-09-08
  • Effects of Coffee Consumption on Fasting Blood Glucose and Insulin Concentrations
    Diabetes Care (IF 11.857) Pub Date : 2004-12-01
    Rob M. van Dam; Wilrike J. Pasman; Petra Verhoef

    Higher habitual coffee consumption was associated with higher insulin sensitivity (1) and a lower risk for type 2 diabetes (2–6) in diverse populations. In contrast, short-term metabolic studies showed that caffeine intake can acutely lower insulin sensitivity (7–9) and increase glucose concentrations (10–15). Randomized intervention studies are needed to examine whether tolerance to these acute effects develops after longer-term consumption (16). We therefore examined the effects of coffee and caffeine on fasting blood concentrations of glucose and insulin over 2–4 weeks in two crossover studies in healthy volunteers.

    更新日期:2017-09-08
  • George Alberti: A Myriad of Contributions to Diabetes and Beyond
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Philip Home

    K. George M.M. Alberti Medawar and Pyke, in Hitler’s Gift (1), record the movement out of Germany in the 1930s of world-class academic talent from within the Jewish diaspora. But among the Jewish migrants was one too young yet to show such talent, indeed a mere toddler, escaping with mother and brother as the door closed in 1939. Kurt George Matthew Mayer Alberti was born in September of 1937. His father William Peter (after the family’s names were duly anglicized) was a printer, and his mother Edith Elizabeth was a research physicist before marriage. Mayer-Alberti-Strasse can still in found in Koblenz, but the young George Alberti settled with his family in Gateshead, U.K.; U.K. citizenship was granted to all in November 1946. The northeast of England was clearly a hit with the young Alberti—he returned later in life from the south of England to be professor of Clinical Biochemistry and subsequently professor of Medicine in Newcastle (see below). But as a lad he crossed the River Tyne to Newcastle’s Royal Grammar School, an institution with a strong record for forwarding its pupils to England’s top universities; George went on to Balliol College Oxford. Balliol is perhaps better known as a cradle of high-flying politicians and civil servants, and this may have confirmed George Alberti’s (partly correct) view of his own personality as “laid back, iconoclastic, irreverent” in an interview for The BMJ in 2016 (2). More Cambridge than Oxford in fact. Young George. Left: George and older brother (Peter) with grandparents (Willi and Hedwig Lachmann) in Koblenz, Germany, prior to the family’s move to England. Middle: George as a schoolboy, circa 1947. Right: George and his mother, Edith, circa 1962 Medical students at Oxford usually studied Animal Physiology as an intercalated Bachelor of Arts degree, and it was not unusual …

    更新日期:2017-09-08
  • In This Issue of Diabetes Care
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    American Diabetes Association

    By Max Bingham, PhD A team-based gaming approach delivering self-managed diabetes education via a mobile app and e-mail can lead to reductions in HbA1c that are comparable to starting a new diabetes medication, according to Kerfoot et al. ( p. 1218 ). They suggest this may represent a scalable solution to improve outcomes among patients with poorly controlled diabetes across wide geographic areas. The spaced education paradigm involves presenting various health scenarios to participants who are then asked to immediately answer multiple-choice questions on the subjects. Following their answers, the participants receive the correct answers combined with an explanation of the topic and a score based on their performance. The material is then presented again to the participants in the following weeks and months to reinforce learning and generate meaningful behavior change. The approach is not unique to diabetes education and has previously been employed in diverse environments such as commercial sales where learning and behavior change are key objectives. Traditional diabetes self-management education has had some success in achieving meaningful short-term reductions in HbA1c. However, the effects reportedly wear off quickly. By modifying the approach to include spaced education, the authors hypothesized that they might be able to generate more sustained HbA1c reductions. In a randomized trial design, the researchers assigned ∼200 patients who are veterans with poorly controlled diabetes to the diabetes self-management education game and ∼200 others to an active control game. They found that the intervention group had significantly greater reductions in HbA1c over 12 months in comparison to control subjects. Going further with a post-hoc analysis, they showed that additional reductions might be possible when baseline HbA1c is particularly high and out of control. Commenting further, author B. Price …

    更新日期:2017-09-08
  • Declines in the Incidence of Diabetes in the U.S.—Real Progress or Artifact?
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Elizabeth Selvin; Mohammed K. Ali

    National surveillance data show a sustained decline in the incidence rate of diagnosed diabetes, which has been heralded as a success in the battle against diabetes in the U.S. In this Perspective, we take a closer look at these data and provide additional insights to help interpret these trends. We examine multiple sources of data on the prevalence and incidence of diabetes in the U.S. as well as data on trends in diabetes risk factors to provide context for these national surveillance findings. Although some of the incidence decline may represent real progress against diabetes, it is likely that there are also nonbiological factors at play, especially changes in diagnostic criteria for diabetes. We present and discuss data that suggest improved detection and changes in screening and diagnostic practices may have resulted in the depletion of the “susceptible population.” Providing this context for the recent declines in new diabetes diagnoses observed in national data is critical to help avoid misinterpretation. We argue that it is premature to declare victory against the epidemic of diabetes in the U.S. and discuss how we might better focus current public health efforts, including a specific emphasis to address prediabetes.

    更新日期:2017-09-08
  • Composite Primary End Points in Cardiovascular Outcomes Trials Involving Type 2 Diabetes Patients: Should Unstable Angina Be Included in the Primary End Point?
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Nikolaus Marx; Darren K. McGuire; Vlado Perkovic; Hans-Juergen Woerle; Uli C. Broedl; Maximilian von Eynatten; Jyothis T. George; Julio Rosenstock

    Reductions in cardiovascular (CV) outcomes in recently reported trials, along with the recent approval by the U.S. Food and Drug Administration of an additional indication for empagliflozin to reduce the risk of CV death in type 2 diabetes patients with evidence of CV disease, have renewed interest in CV outcome trials (CVOTs) of glucose-lowering drugs. Composite end points are a pragmatic necessity in CVOTs to ensure that sample size and duration of follow-up remain reasonable. Combining clinical outcomes into a composite end point increases the numbers of events ascertained and thus statistical power and precision. Historically, composite CV end points in diabetes trials have included a larger number of components, while more recent CVOTs almost exclusively use a composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke—the so-called three-point major adverse CV event (3P-MACE) composite—or add hospitalization for unstable angina (HUA) to these three outcomes (4P-MACE). The inclusion of HUA increases the number of events for analysis, but noteworthy disadvantages include clinical subjectivity in ascertainment of HUA and its lower prognostic relevance compared with CV death, MI, or stroke. Furthermore, results from recent CVOTs indicate that glucose-lowering agents seem to have minimal impact on HUA. Its inclusion therefore potentially favors a shift of the hazard ratio (HR) toward the null, which is especially problematic in trials designed to demonstrate noninferiority. The primary outcome of 3P-MACE may offer a better balance than 4P-MACE between statistical efficiency, operational complexity, the likelihood of diagnostic precision (and therefore clinical relevance) for each of the component outcomes, clinical importance, and the aim to adequately capture any potential treatment effect of the intervention. Nevertheless, as individual medications may mechanistically differ in their impact on CV outcomes, no particular individual or composite end point can be seen as a “gold standard” for CVOTs of all glucose-lowering drugs.

    更新日期:2017-09-08
  • The War Is Not Yet Won
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Laura A. Young; John B. Buse

    In this issue of Diabetes Care , Selvin and Ali (1) have done a masterful job of exploring and explaining both the rise in the incidence of diabetes over 20 years and the fall in the incidence of diabetes over the last 5 years in the U.S. You may want to skip this and just read their article. The bottom line is that we as clinicians can confirm that they, as epidemiologists, have almost certainly gotten it right. Importantly, their analysis has critical implications for policy makers. There are a couple of critical definitions that need to be clarified. First, the term “incidence” refers to an annual rate of new diagnoses. That is the feature of diabetes explored in this article and here refers specifically to the number of people who report in a survey that a health care professional told them for the first time that they had diabetes in the last year. That number has dropped about 20% since 2009 (2). Incidence needs to be distinguished from “prevalence,” which refers to the number or proportion affected by a condition. For diabetes, that is a number that continues to rise and is only peripherally addressed (3). While clinicians tend to not focus on research methodology, in this case the methods are crucial to understand. The data from which incidence rates are derived is national survey data. These data …

    更新日期:2017-09-08
  • George Alberti: A Myriad of Contributions to Diabetes and Beyond
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Philip Home

    K. George M.M. Alberti Medawar and Pyke, in Hitler’s Gift (1), record the movement out of Germany in the 1930s of world-class academic talent from within the Jewish diaspora. But among the Jewish migrants was one too young yet to show such talent, indeed a mere toddler, escaping with mother and brother as the door closed in 1939. Kurt George Matthew Mayer Alberti was born in September of 1937. His father William Peter (after the family’s names were duly anglicized) was a printer, and his mother Edith Elizabeth was a research physicist before marriage. Mayer-Alberti-Strasse can still in found in Koblenz, but the young George Alberti settled with his family in Gateshead, U.K.; U.K. citizenship was granted to all in November 1946. The northeast of England was clearly a hit with the young Alberti—he returned later in life from the south of England to be professor of Clinical Biochemistry and subsequently professor of Medicine in Newcastle (see below). But as a lad he crossed the River Tyne to Newcastle’s Royal Grammar School, an institution with a strong record for forwarding its pupils to England’s top universities; George went on to Balliol College Oxford. Balliol is perhaps better known as a cradle of high-flying politicians and civil servants, and this may have confirmed George Alberti’s (partly correct) view of his own personality as “laid back, iconoclastic, irreverent” in an interview for The BMJ in 2016 (2). More Cambridge than Oxford in fact. Young George. Left: George and older brother (Peter) with grandparents (Willi and Hedwig Lachmann) in Koblenz, Germany, prior to the family’s move to England. Middle: George as a schoolboy, circa 1947. Right: George and his mother, Edith, circa 1962 Medical students at Oxford usually studied Animal Physiology as an intercalated Bachelor of Arts degree, and it was not unusual …

    更新日期:2017-09-08
  • Diabetes in a Large Dementia Cohort: Clinical Characteristics and Treatment From the Swedish Dementia Registry
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Juraj Secnik; Pavla Cermakova; Seyed-Mohammad Fereshtehnejad; Pontus Dannberg; Kristina Johnell; Johan Fastbom; Bengt Winblad; Maria Eriksdotter; Dorota Religa

    OBJECTIVE We aimed to investigate the differences in clinical characteristics and pharmacological treatment associated with the presence of diabetes in a large cohort of patients with dementia. RESEARCH DESIGN AND METHODS A cross-sectional registry-based study was conducted using data from the Swedish Dementia Registry (SveDem). Data on dementia diagnosis, dementia type, and demographic determinants were extracted from SveDem. Data from the Swedish Patient Register and Prescribed Drug Register were combined for the diagnosis of diabetes. Data on antidiabetic, dementia, cardiovascular, and psychotropic medications were extracted from the Swedish Prescribed Drug Register. Logistic regression was used to determine whether the variables were associated with diabetes after adjustment for confounders. In total, 29,630 patients were included in the study, and 4,881 (16.5%) of them received a diagnosis of diabetes. RESULTS In the fully adjusted model, diabetes was associated with lower age at dementia diagnosis (odds ratio [OR] 0.97 [99% CI 0.97–0.98]), male sex (1.41 [1.27–1.55]), vascular dementia (1.17 [1.01–1.36]), and mixed dementia (1.21 [1.06–1.39]). Dementia with Lewy bodies (0.64 [0.44–0.94]), Parkinson disease dementia (0.46 [0.28–0.75]), and treatment with antidepressants (0.85 [0.77–0.95]) were less common among patients with diabetes. Patients with diabetes who had Alzheimer disease obtained significantly less treatment with cholinesterase inhibitors (0.78 [0.63–0.95]) and memantine (0.68 [0.54–0.85]). CONCLUSIONS Patients with diabetes were younger at dementia diagnosis and obtained less dementia medication for Alzheimer disease, suggesting less optimal dementia treatment. Future research should evaluate survival and differences in metabolic profile in patients with diabetes and different dementia disorders.

    更新日期:2017-09-08
  • My Child Is Islet Autoantibody Positive: Impact on Parental Anxiety
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Suzanne Bennett Johnson; Kristian F. Lynch; Roswith Roth; Desmond Schatz; the TEDDY Study Group

    OBJECTIVE To assess parent anxiety in response to genetic and islet autoantibody (IA) testing in children at increased genetic risk for type 1 diabetes followed from birth in The Environmental Determinants of Diabetes in the Young (TEDDY) study. RESEARCH DESIGN AND METHODS Parent anxiety about TEDDY children’s risk was assessed with the State Anxiety Inventory (SAI). Parents completed the SAI when the child was 3, 6, and 15 months old and annually thereafter. Children were tested for IA every 3 months for 4 years and every 6 months thereafter. Parent SAI scores of 6,799 children followed with IA testing for at least 1 and up to 6 years were examined. RESULTS At study inception, parents showed high levels of anxiety in response to their child’s increased genetic type 1 diabetes risk; mothers were more anxious than fathers, and parents with diabetes in the family were more anxious than parents with no family history. In response to repeated IA-negative (IA−) test results, parent anxiety declined to normal levels. Anxiety increased in parents faced with an IA-positive (IA+) test result. Parents faced with two or more types of IA+ test results showed particularly high levels of anxiety (all P < 0.001). CONCLUSIONS Infant genetic screening for type 1 diabetes raises parent anxiety when the child is at increased risk, but anxiety dissipates over time in cases of repeated IA− results. IA+ results heighten parent anxiety, and parents faced with two or more types of IA+ results may experience considerable anxiety for longer periods.

    更新日期:2017-09-08
  • Improvement in Glycemic Control of Type 2 Diabetes After Successful Treatment of Hepatitis C Virus
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Justine Hum; Janice H. Jou; Pamela K. Green; Kristin Berry; James Lundblad; Barbara D. Hettinger; Michael Chang; George N. Ioannou

    OBJECTIVE Hepatitis C virus (HCV) infection is associated with diabetes and may worsen glycemic control in patients with diabetes. We aimed to investigate whether eradication of HCV infection with direct-acting antiviral (DAA) agents is associated with improved glycemic control in patients with diabetes. RESEARCH DESIGN AND METHODS We identified 2,435 patients with diabetes who underwent interferon-free and ribavirin-free DAA-based antiviral treatment for HCV in the national Veterans Affairs health care system. Changes in average hemoglobin A1c (HbA1c) level and use of antidiabetic medications 1 year before and after antiviral treatment were compared between patients who achieved sustained virologic response (SVR) and those who did not. RESULTS Among patients with elevated baseline HbA1c, the drop in HbA1c associated with antiviral treatment was greater in those who achieved SVR (0.98%) than in those who sustained treatment failure (0.65%) (adjusted mean difference 0.34, P = 0.02). Use of antidiabetic medications decreased more in patients who achieved SVR than in those who sustained treatment failure, especially for the use of insulin, which dropped significantly from 41.3% to 38% in patients achieving SVR compared with a slight increase from 49.8% to 51% in those who sustained treatment failure. CONCLUSIONS DAA-based eradication of HCV is associated with improved glycemic control in patients with diabetes as evidenced by decreased mean HbA1c and decreased insulin use. These endocrine benefits of SVR provide additional justification for considering antiviral treatment in all patients with diabetes.

    更新日期:2017-09-08
  • Poor Reliability and Poor Adherence to Self-Monitoring of Blood Glucose Are Common in Women With Gestational Diabetes Mellitus and May Be Associated With Poor Pregnancy Outcomes
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Emmanuel Cosson; Baz Baz; Françoise Gary; Isabelle Pharisien; Minh Tuan Nguyen; Dorian Sandre-Banon; Yahya Jaber; Camille Cussac-Pillegand; Isabela Banu; Lionel Carbillon; Paul Valensi

    OBJECTIVE To evaluate the compliance with self-monitoring of blood glucose (SMBG) and the reliability of diabetes logbooks in women with gestational diabetes mellitus (GDM), as well as the associated determinants and outcomes. RESEARCH DESIGN AND METHODS We prospectively selected French-speaking women with newly diagnosed GDM who had been referred to our diabetes management program and understood SMBG principles. At the next follow-up visit, we collected SMBG results from glucose meters and logbooks. We analyzed pregnancy outcomes. RESULTS Data were analyzed over 13 ± 3 days in 91 women. Only 61.5% had performed ≥80% of the required tests. Poor compliance was associated with a family history of diabetes, social deprivation, and non-European origin. The average time between pre- and postprandial tests was 141 ± 20 min, with 46.5% of women performing ≥80% of postprandial measurements 100–140 min after meals. Inadequate timing was associated with ethnicity and higher HbA1c at baseline. A total of 23.1% of women had <90% matched values in diary and meter memory, and a poor concordance was associated with a family history of diabetes. Poor adherence was associated with more preeclampsia (12.2 vs. 1.9%, P = 0.049), and inadequate postprandial test timing with a higher HbA1c at delivery (5.3 ± 0.4 vs. 5.0 ± 0.3% [34 ± 2 vs. 31 ± 2 mmol/mol], P < 0.01), despite more frequent insulin therapy. CONCLUSIONS Although women with GDM are considered to be highly motivated, SMBG adherence and reliability are of concern and may be associated with poor gestational prognosis, suggesting that caregivers should systematically check the glucose meter memory to improve GDM management.

    更新日期:2017-09-08
  • Hemoglobin A1c Variability Predicts Symptoms of Depression in Elderly Individuals With Type 2 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Ramit Ravona-Springer; Anthony Heymann; James Schmeidler; Erin Moshier; Elizabeth Guerrero-Berroa; Laili Soleimani; Mary Sano; Derek Leroith; Rachel Preiss; Ruth Tzukran; Jeremy M. Silverman; Michal Schnaider Beeri

    OBJECTIVE This study aimed to analyze the relationship of variability in hemoglobin A1c (HbA1c) over years with subsequent depressive symptoms. RESEARCH DESIGN AND METHODS Subjects (n = 837) were participants of the Israel Diabetes and Cognitive Decline (IDCD) study, which aimed to examine the relationship of characteristics of long-term type 2 diabetes with cognitive decline. All pertain to a diabetes registry established in 1998, which contains an average of 18 HbA1c measurements per subject. The results presented here are based on the IDCD baseline examination. Symptoms of depression were assessed using the 15-item version of the Geriatric Depression Scale (GDS). To quantify the association between variability in glycemic control (measured as the SD of HbA1c measurements [HbA1c-SD]) since 1998 with the number of depression symptoms at IDCD baseline, incidence rate ratios (IRRs) and corresponding 95% CIs were estimated via negative binomial regression modeling and used to account for the overdispersion in GDS scores. RESULTS Subjects’ ages averaged 72.74 years (SD 4.63 years), and the mean number of years in the diabetes registry was 8.7 (SD 2.64 years). The mean GDS score was 2.16 (SD 2.26); 10% of subjects had a GDS score ≥6, the cutoff for clinically significant depression. Mean HbA1c significantly correlated with HbA1c-SD (r = 0.6625; P < 0.0001). The SD, but not the mean, of HbA1c measurements was significantly associated with the number of subsequent depressive symptoms. For each additional 1% increase in HbA1c-SD, the number of depressive symptoms increased by a factor of 1.31 (IRR = 1.31 [95% CI 1.03–1.67]; P = 0.03). CONCLUSIONS Variability in glycemic control is associated with more depressive symptoms.

    更新日期:2017-09-08
  • Genetic and Environmental Interactions Modify the Risk of Diabetes-Related Autoimmunity by 6 Years of Age: The TEDDY Study
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Jeffrey P. Krischer; Kristian F. Lynch; Åke Lernmark; William A. Hagopian; Marian J. Rewers; Jin-Xiong She; Jorma Toppari; Anette-G. Ziegler; Beena Akolkar; the TEDDY Study Group

    OBJECTIVE We tested the associations between genetic background and selected environmental exposures with respect to islet autoantibodies and type 1 diabetes. RESEARCH DESIGN AND METHODS Infants with HLA-DR high-risk genotypes were prospectively followed for diabetes-related autoantibodies. Single nucleotide polymorphisms (SNPs) came from the Illumina ImmunoChip and environmental exposure data were by parental report. Children were followed to age 6 years. RESULTS Insulin autoantibodies occurred earlier than GAD antibody (GADA) and then declined, while GADA incidence rose and remained constant (significant in HLA-DR4 but not in the DR3/3 children). The presence of SNPs rs2476601 (PTPN22) and rs2292239 (ERBB3) demonstrated increased risk of both autoantibodies to insulin (IAA) only and GADA only. SNP rs689 (INS) was protective of IAA only, but not of GADA only. The rs3757247 (BACH2) SNP demonstrated increased risk of GADA only. Male sex, father or sibling as the diabetic proband, introduction of probiotics under 28 days of age, and weight at age 12 months were associated with IAA only, but only father as the diabetic proband and weight at age 12 months were associated with GADA only. Mother as the diabetic proband was not a significant risk factor. CONCLUSIONS These results show clear differences in the initiation of autoimmunity according to genetic factors and environmental exposures that give rise to IAA or GADA as the first appearing indication of autoimmunity.

    更新日期:2017-09-08
  • Cardiac Stress and Inflammatory Markers as Predictors of Heart Failure in Patients With Type 2 Diabetes: The ADVANCE Trial
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Toshiaki Ohkuma; Min Jun; Mark Woodward; Sophia Zoungas; Mark E. Cooper; Diederick E. Grobbee; Pavel Hamet; Giuseppe Mancia; Bryan Williams; Paul Welsh; Naveed Sattar; Jonathan E. Shaw; Kazem Rahimi; John Chalmers

    OBJECTIVE This study examined the individual and combined effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and hs-CRP on the prediction of heart failure incidence or progression in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A nested case-cohort study was conducted in 3,098 participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. RESULTS A higher value of each biomarker was significantly associated with a higher risk of heart failure incidence or progression, after adjustment for major risk factors. The hazard ratios per 1-SD increase were 3.06 (95% CI 2.37, 3.96) for NT-proBNP, 1.50 (1.27, 1.77) for hs-cTnT, 1.48 (1.27, 1.72) for IL-6, and 1.32 (1.12, 1.55) for hs-CRP. The addition of NT-proBNP to the model including conventional risk factors meaningfully improved 5-year risk-predictive performance (C statistic 0.8162 to 0.8800; continuous net reclassification improvement [NRI] 73.1%; categorical NRI [<5%, 5–10%, >10% 5-year risk] 24.2%). In contrast, the addition of hs-cTnT, IL-6, or hs-CRP did not improve the prediction metrics consistently in combination or when added to NT-proBNP. CONCLUSIONS Only NT-proBNP strongly and consistently improved the prediction of heart failure in patients with type 2 diabetes beyond a wide range of clinical risk factors and biomarkers.

    更新日期:2017-09-08
  • Visit-to-Visit Variations in Fasting Plasma Glucose and HbA1c Associated With an Increased Risk of Alzheimer Disease: Taiwan Diabetes Study
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Tsai-Chung Li; Chun-Pai Yang; Shih-Ting Tseng; Chia-Ing Li; Chiu-Shong Liu; Wen-Yuan Lin; Kai-Lin Hwang; Sing-Yu Yang; Jen-Huai Chiang; Cheng-Chieh Lin

    OBJECTIVE The relationship between glycemic variability and the incidence of Alzheimer disease (AD) in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to examine visit-to-visit variations in fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) represented by the coefficient of variation (CV) and to determine whether they were independently associated with AD, irrespective of HbA1c and other traditional risk factors in such patients. RESEARCH DESIGN AND METHODS Patients with T2DM enrolled in the National Diabetes Care Management Program, age ≥60 years, and without diagnosis of AD (n = 16,706) were included in the study. Potential risk factors were analyzed using extended Cox proportional hazards regression models for competing risk of mortality on AD incidence. RESULTS During a median follow-up of 8.88 years, 831 incident cases of AD were identified, with a crude incidence rate of 3.5/1,000 person-years. After adjustment for sociodemographic factors, lifestyle behaviors, diabetes-related variables, FPG and HbA1c, drug-related variables, and comorbidities, both FPG CV and HbA1c CV were found to be significant predictors of AD, with corresponding hazard ratios of 1.27 (95% CI 1.06–1.52) for the third tertile in FPG CV and 1.32 (95% CI 1.11–1.58) for the third tertile in HbA1c CV. CONCLUSIONS FPG CV and HbA1c CV are independently associated with AD. The associations between glycemic variability and AD demonstrated in this study suggest a linked pathophysiological mechanism, which is worthy of further investigation. Further research is required to confirm our results and to evaluate whether FPG CV and HbA1c CV can be valuable therapeutic targets for patients with T2DM at risk.

    更新日期:2017-09-08
  • A Team-Based Online Game Improves Blood Glucose Control in Veterans With Type 2 Diabetes: A Randomized Controlled Trial
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    B. Price Kerfoot; David R. Gagnon; Graham T. McMahon; Jay D. Orlander; Katherine E. Kurgansky; Paul R. Conlin

    OBJECTIVE Rigorous evidence is lacking whether online games can improve patients’ longer-term health outcomes. We investigated whether an online team-based game delivering diabetes self-management education (DSME) to patients via e-mail or mobile application (app) can generate longer-term improvements in hemoglobin A1c (HbA1c). RESEARCH DESIGN AND METHODS Patients ( n = 456) on oral diabetes medications with HbA1c ≥58 mmol/mol were randomly assigned between a DSME game (with a civics booklet) and a civics game (with a DSME booklet). The 6-month games sent two questions twice weekly via e-mail or mobile app. Participants accrued points based on performance, with scores posted on leaderboards. Winning teams and individuals received modest financial rewards. Our primary outcome measure was HbA1c change over 12 months. RESULTS DSME game patients had significantly greater HbA1c reductions over 12 months than civics game patients (−8 mmol/mol [95% CI −10 to −7] and −5 mmol/mol [95% CI −7 to −3], respectively; P = 0.048). HbA1c reductions were greater among patients with baseline HbA1c >75 mmol/mol: −16 mmol/mol [95% CI −21 to −12] and −9 mmol/mol [95% CI −14 to −5] for DSME and civics game patients, respectively; P = 0.031. CONCLUSIONS Patients with diabetes who were randomized to an online game delivering DSME demonstrated sustained and meaningful HbA1c improvements. Among patients with poorly controlled diabetes, the DSME game reduced HbA1c by a magnitude comparable to starting a new diabetes medication. Online games may be a scalable approach to improve outcomes among geographically dispersed patients with diabetes and other chronic diseases.

    更新日期:2017-09-08
  • Prevalence of and Risk Factors for Diabetic Peripheral Neuropathy in Youth With Type 1 and Type 2 Diabetes: SEARCH for Diabetes in Youth Study
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Mamta Jaiswal; Jasmin Divers; Dana Dabelea; Scott Isom; Ronny A. Bell; Catherine L. Martin; David J. Pettitt; Sharon Saydah; Catherine Pihoker; Debra A. Standiford; Lawrence M. Dolan; Santica Marcovina; Barbara Linder; Angela D. Liese; Rodica Pop-Busui; Eva L. Feldman

    OBJECTIVE We assessed the prevalence of and risk factors for diabetic peripheral neuropathy (DPN) in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) enrolled in the SEARCH for Diabetes in Youth (SEARCH) study. RESEARCH DESIGN AND METHODS The Michigan Neuropathy Screening Instrument (MNSI) was used to assess DPN in 1,734 youth with T1D (mean ± SD age 18 ± 4 years, T1D duration 7.2 ± 1.2 years, and HbA1c 9.1 ± 1.9%) and 258 youth with T2D (age 22 ± 3.5 years, T2D duration 7.9 ± 2 years, and HbA1c 9.4 ± 2.3%) who were enrolled in the SEARCH study and had ≥5 years of diabetes duration. DPN was defined as an MNSI exam score of >2. Glycemic control over time was estimated as area under the curve for HbA1c. RESULTS The prevalence of DPN was 7% in youth with T1D and 22% in youth with T2D. Risk factors for DPN in youth with T1D were older age, longer diabetes duration, smoking, increased diastolic blood pressure, obesity, increased LDL cholesterol and triglycerides, and lower HDL cholesterol (HDL-c). In youth with T2D, risk factors were older age, male sex, longer diabetes duration, smoking, and lower HDL-c. Glycemic control over time was worse among those with DPN compared with those without for youth with T1D (odds ratio 1.53 [95% CI 1.24; 1.88]) but not for youth with T2D (1.05 [0.7; 1.56]). CONCLUSIONS The high rates of DPN among youth with diabetes are a cause of concern and suggest a need for early screening and better risk factor management. Interventions in youth that address poor glycemic control and dyslipidemia may prevent or delay debilitating neuropathic complications.

    更新日期:2017-09-08
  • The Prognostic Value of Fasting Plasma Glucose, Two-Hour Postload Glucose, and HbA1c in Patients With Coronary Artery Disease: A Report From EUROASPIRE IV
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Bahira Shahim; Dirk De Bacquer; Guy De Backer; Viveca Gyberg; Kornelia Kotseva; Linda Mellbin; Oliver Schnell; Jaakko Tuomilehto; David Wood; Lars Rydén

    OBJECTIVE Three tests are recommended for identifying dysglycemia: fasting glucose (FPG), 2-h postload glucose (2h-PG) from an oral glucose tolerance test (OGTT), and glycated hemoglobin A1c (HbA1c). This study explored the prognostic value of these screening tests in patients with coronary artery disease (CAD). RESEARCH DESIGN AND METHODS FPG, 2h-PG, and HbA1c were used to screen 4,004 CAD patients without a history of diabetes (age 18–80 years) for dysglycemia. The prognostic value of these tests was studied after 2 years of follow-up. The primary end point included cardiovascular mortality, nonfatal myocardial infarction, stroke, or hospitalization for heart failure and a secondary end point of incident diabetes. RESULTS Complete information including all three glycemic parameters was available in 3,775 patients (94.3%), of whom 246 (6.5%) experienced the primary end point. Neither FPG nor HbA1c predicted the primary outcome, whereas the 2h-PG, dichotomized as <7.8 vs. ≥7.8 mmol/L, was a significant predictor (hazard ratio 1.38, 95% CI 1.07–1.78; P = 0.01). During follow-up, diabetes developed in 78 of the 2,609 patients (3.0%) without diabetes at baseline. An FPG between 6.1 and 6.9 mmol/L did not predict incident diabetes, whereas HbA1c 5.7–6.5% and 2h-PG 7.8–11.0 mmol/L were both significant independent predictors. CONCLUSIONS The 2h-PG, in contrast to FPG and HbA1c, provides significant prognostic information regarding cardiovascular events in patients with CAD. Furthermore, elevated 2h-PG and HbA1c are significant prognostic indicators of an increased risk of incident diabetes.

    更新日期:2017-09-08
  • Computed Tomography Angiography Images of Coronary Artery Stenosis Provide a Better Prediction of Risk Than Traditional Risk Factors in Asymptomatic Individuals With Type 2 Diabetes: A Long-term Study of Clinical Outcomes
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Kwan Yong Lee; Byung-Hee Hwang; Tae-Hoon Kim; Chan Jun Kim; Jin-Jin Kim; Eun-Ho Choo; Ik Jun Choi; Young Choi; Ha-Wook Park; Yoon-Seok Koh; Pum-Joon Kim; Jong Min Lee; Mi-Jeong Kim; Doo Soo Jeon; Jae-Hyoung Cho; Jung Im Jung; Ki-Bae Seung; Kiyuk Chang

    OBJECTIVE We investigated the efficacy of coronary computed tomography angiography (CCTA) in predicting the long-term risks in asymptomatic patients with type 2 diabetes and compared it with traditional risk factors. RESEARCH DESIGN AND METHODS We analyzed 933 patients with asymptomatic type 2 diabetes who underwent CCTA. Stenosis was considered obstructive (≥50%) in each coronary artery segment using CCTA. The extent and severity scores for coronary artery disease (CAD) were evaluated. The primary end point was major adverse cardiovascular events (MACE), including all-cause mortality, nonfatal myocardial infarction, and late coronary revascularization during a mean follow-up period of 5.5 ± 2.1 years. RESULTS Ninety-four patients with MACE exhibited obstructive CAD with a greater extent and higher severity scores (P < 0.001 for all). After adjusting for confounding risk factors, obstructive CAD remained an independent predictor of MACE (hazard ratio 3.11 [95% CI 2.00–4.86]; P < 0.001]). The performance of a risk prediction model based on C-statistics was significantly improved (C-index 0.788 [95% CI 0.747–0.829]; P = 0.0349) upon the addition of a finding of obstructive CAD using CCTA to traditional risk factors, including age, male, hypertension, hyperlipidemia, smoking, estimated glomerular filtration rate, and HbA1c. Both integrated discrimination improvement (IDI) and net reclassification improvement (NRI) analyses further supported this finding (IDI 0.046 [95% CI 0.020–0.072], P < 0.001, and NRI 0.55 [95% CI 0.343–0.757], P < 0.001). In contrast, the risk prediction power of the coronary artery calcium score remained unimproved (C-index 0.740, P = 0.547). CONCLUSIONS Based on our data, the addition of CCTA-detected obstructive CAD to models that include traditional risk factors improves the predictions of MACE in asymptomatic patients with type 2 diabetes.

    更新日期:2017-09-08
  • Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes Predicts Poor Long-term Glycemic Control
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Lindsey M. Duca; Bing Wang; Marian Rewers; Arleta Rewers

    OBJECTIVE This study tested the hypothesis that diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in children predicts poor long-term glycemic control independently of established risk factors. RESEARCH DESIGN AND METHODS This was a prospective cohort study of 3,364 Colorado residents diagnosed with type 1 diabetes before 18 years of age, in 1998–2012, and monitored for up to 15 years. Of those, 1,297 (39%) had DKA at diagnosis (blood glucose >250 mg/dL, and venous pH <7.3 or bicarbonate <15 mEq/L). Severity of DKA was further classified as mild/moderate (pH 7.10–7.29 or bicarbonate 5–14 mEq/L) or severe (pH <7.10 or bicarbonate <5 mEq/L). HbA1c levels were measured an average of 2.8 times/year (median 20 HbA1c values/patient). A linear mixed model was used to examine the effect of DKA on long-term HbA1c levels, adjusting for age, race/ethnicity, sex, family history of diabetes, health insurance, and insulin pump use. RESULTS DKA at diagnosis predicted persistently elevated HbA1c levels. Compared with children without DKA, HbA1c tracked 1.4% (15.3 mmol/mol) higher in those with severe DKA (P < 0.0001) and 0.9% (9.8 mmol/mol) higher in those with mild/moderate DKA at diagnosis (P < 0.0001). These effects were independent of ethnic minority status or lack of health insurance at diagnosis that predicted higher HbA1c by 0.5% (5.5 mmol/mol; P < 0.0001) and 0.2% (2.2 mmol/mol; P < 0.0001), respectively. Insulin pump use or having a parent or sibling with type 1 diabetes predicted lower long-term HbA1c by, respectively, 0.4% (4.4 mmol/mol; P < 0.0001) and 0.2% (2.2 mmol/mol; P = 0.01). CONCLUSIONS DKA at diagnosis of type 1 diabetes in children predicts poor long-term glycemic control, independent of demographic and socioeconomic factors.

    更新日期:2017-09-08
  • Skeletal Muscle Microvascular-Linked Improvements in Glycemic Control From Resistance Training in Individuals With Type 2 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Ryan D. Russell; Donghua Hu; Timothy Greenaway; Sarah J. Blackwood; Renee M. Dwyer; James E. Sharman; Graeme Jones; Kathryn A. Squibb; Aascha A. Brown; Petr Otahal; Meg Boman; Hayder Al-Aubaidy; Dino Premilovac; Christian K. Roberts; Samuel Hitchins; Stephen M. Richards; Stephen Rattigan; Michelle A. Keske

    OBJECTIVE Insulin increases glucose disposal in part by enhancing microvascular blood flow (MBF) and substrate delivery to myocytes. Insulin’s microvascular action is impaired with insulin resistance and type 2 diabetes. Resistance training (RT) improves glycemic control and insulin sensitivity, but whether this improvement is linked to augmented skeletal muscle microvascular responses in type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS Seventeen (11 male and 6 female; 52 ± 2 years old) sedentary patients with type 2 diabetes underwent 6 weeks of whole-body RT. Before and after RT, participants who fasted overnight had clinical chemistries measured (lipids, glucose, HbA1c, insulin, and advanced glycation end products) and underwent an oral glucose challenge (OGC) (50 g × 2 h). Forearm muscle MBF was assessed by contrast-enhanced ultrasound, skin MBF by laser Doppler flowmetry, and brachial artery flow by Doppler ultrasound at baseline and 60 min post-OGC. A whole-body DEXA scan before and after RT assessed body composition. RESULTS After RT, muscle MBF response to the OGC increased, while skin microvascular responses were unchanged. These microvascular adaptations were accompanied by improved glycemic control (fasting blood glucose, HbA1c, and glucose area under the curve [AUC] during OGC) and increased lean body mass and reductions in fasting plasma triglyceride, total cholesterol, advanced glycation end products, and total body fat. Changes in muscle MBF response after RT significantly correlated with reductions in fasting blood glucose, HbA1c, and OGC AUC with adjustment for age, sex, % body fat, and % lean mass. CONCLUSIONS RT improves OGC-stimulated muscle MBF and glycemic control concomitantly, suggesting that MBF plays a role in improved glycemic control from RT.

    更新日期:2017-09-08
  • Exercise Training Improves but Does Not Normalize Left Ventricular Systolic and Diastolic Function in Adolescents With Type 1 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-09-01
    Silmara Gusso; Teresa Pinto; James C. Baldi; José G.B. Derraik; Wayne S. Cutfield; Tim Hornung; Paul L. Hofman

    OBJECTIVE To determine the impact of 20 weeks of exercise training in aerobic capacity on left ventricular function and glycemic control in adolescents with and without type 1 diabetes. RESEARCH DESIGN AND METHODS Fifty-three adolescents with type 1 diabetes (aged 15.6 years) were divided into two groups: exercise training ( n = 38) and nontraining ( n = 15). Twenty-two healthy adolescents without diabetes (aged 16.7 years) were included and, with the 38 participants with type 1 diabetes, participated in a 20-week exercise-training intervention. Assessments included VO2max and body composition. Left ventricular parameters were obtained at rest and during acute exercise using MRI. RESULTS Exercise training improved aerobic capacity (10%) and stroke volume (6%) in both trained groups, but the increase in the group with type 1 diabetes remained lower than trained control subjects. Increased stroke volume in adolescents with type 1 diabetes resulted from greater left ventricular contractility (9% increase in ejection fraction and an 11% reduction in end-systolic volumes) and, to a lesser extent, improved left ventricular filling (6%), suggesting that impaired diastolic function can be affected by exercise training in adolescents with type 1 diabetes. Insulin use decreased by ∼10%, but no change in glycemic status was observed. CONCLUSIONS These data demonstrate that in adolescents, the impairment in left ventricular function seen with type 1 diabetes can be improved, although not normalized, with regular intense physical activity. Importantly, diastolic dysfunction, a common mechanism causing heart failure in older subjects with diabetes, appears to be partially reversible in this age group.

    更新日期:2017-09-08
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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