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  • Increased Liver Fatty Acid Uptake Is Partly Reversed and Liver Fat Content Normalized After Bariatric Surgery
    Diabetes Care (IF 11.857) Pub Date : 2017-11-17
    Heidi Immonen; Jarna C. Hannukainen; Nobuyuki Kudomi; Jussi Pihlajamäki; Virva Saunavaara; Jukka Laine; Paulina Salminen; Terho Lehtimäki; Tam Pham; Patricia Iozzo; Pirjo Nuutila

    OBJECTIVE Changes in liver fatty acid metabolism are important in understanding the mechanisms of diabetes remission and metabolic changes after bariatric surgery. RESEARCH DESIGN AND METHODS Liver fatty acid uptake (LFU), blood flow, and fat content (LFC) were measured in 25 obese subjects before bariatric surgery and 6 months after using positron emission tomography/computed tomography and MRS; 14 lean individuals served as the control subjects. RESULTS The increased LFU in obese subjects was associated with body adiposity. LFU was reduced postoperatively but was still high compared with the control subjects. LFC was normalized. Liver blood flow (per unit volume) was higher in obese subjects than in the control subjects at baseline and was further increased postoperatively; however, the total organ blood flow was unchanged as the liver volume decreased. CONCLUSIONS The findings suggest that in a postoperative state, intrahepatic fatty acids are not stored in the liver but are used for oxidation to provide energy. Changes in perfusion may contribute to improved liver metabolism postoperatively.

    更新日期:2017-11-20
  • Objectively Measured Physical Activity and Sedentary Time Are Associated With Cardiometabolic Risk Factors in Adults With Prediabetes: The PREVIEW Study
    Diabetes Care (IF 11.857) Pub Date : 2017-11-17
    Nils Swindell; Kelly Mackintosh; Melitta McNarry; Jeffrey W. Stephens; Diewertje Sluik; Mikael Fogelholm; Mathijs Drummen; Ian MacDonald; J. Alfredo Martinez; Teodora Handjieva-Darlenska; Sally D. Poppitt; Jennie Brand-Miller; Thomas M. Larsen; Anne Raben; Gareth Stratton

    OBJECTIVE The aim of the present cross-sectional study was to examine the association among physical activity (PA), sedentary time (ST), and cardiometabolic risk in adults with prediabetes. RESEARCH DESIGN AND METHODS Participants (n = 2,326; 25–70 years old, 67% female) from eight countries, with a BMI >25 kg ⋅ m−2 and impaired fasting glucose (5.6–6.9 mmol ⋅ L−1) or impaired glucose tolerance (7.8–11.0 mmol ⋅ L−1 at 2 h), participated. Seven-day accelerometry objectively assessed PA levels and ST. RESULTS Multiple linear regression revealed that moderate-to-vigorous PA (MVPA) was negatively associated with HOMA of insulin resistance (HOMA-IR) (standardized β = −0.078 [95% CI −0.128, −0.027]), waist circumference (WC) (β = −0.177 [−0.122, −0.134]), fasting insulin (β = −0.115 [−0.158, −0.072]), 2-h glucose (β = −0.069 [−0.112, −0.025]), triglycerides (β = −0.091 [−0.138, −0.044]), and CRP (β = −0.086 [−0.127, −0.045]). ST was positively associated with HOMA-IR (β = 0.175 [0.114, 0.236]), WC (β = 0.215 [0.026, 0.131]), fasting insulin (β = 0.155 [0.092, 0.219]), triglycerides (β = 0.106 [0.052, 0.16]), CRP (β = 0.106 [0.39, 0.172]), systolic blood pressure (BP) (β = 0.078 [0.026, 0.131]), and diastolic BP (β = 0.106 [0.39, −0.172]). Associations reported between total PA (counts ⋅ min−1) and all risk factors were comparable or stronger than for MVPA: HOMA-IR (β = −0.151 [−0.194, −0.107]), WC (β = −0.179 [−0.224, −0.134]), fasting insulin (β = −0.139 [−0.183, −0.096]), 2-h glucose (β = −0.088 [−0.131, −0.045]), triglycerides (β = −0.117 [−0.162, −0.071]), and CRP (β = −0.104 [−0.146, −0.062]). CONCLUSIONS In adults with prediabetes, objectively measured PA and ST were associated with cardiometabolic risk markers. Total PA was at least as strongly associated with cardiometabolic risk markers as MVPA, which may imply that the accumulation of total PA over the day is as important as achieving the intensity of MVPA.

    更新日期:2017-11-20
  • Impact of the 2013 National Rollout of CMS Competitive Bidding Program: the Disruption Continues
    Diabetes Care (IF 11.857) Pub Date : 2017-11-16
    Gary A. Puckrein; Irl B. Hirsch; Christopher G. Parkin; Bruce T. Taylor; Liou Xu; David G. Marrero

    OBJECTIVE Use of glucose monitoring is essential to the safety of individuals with insulin-treated diabetes. In 2011, the Centers for Medicare & Medicaid Services (CMS) implemented the Medicare Competitive Bidding Program (CBP) in nine test markets. This resulted in a substantial disruption of beneficiary access to self-monitoring of blood glucose (SMBG) supplies and significant increases in the percentage of beneficiaries with either reduced or no acquisition of supplies. These reductions were significantly associated with increased mortality, hospitalizations, and costs. The CBP was implemented nationally in July 2013. We evaluated the impact of this rollout to determine if the adverse outcomes seen in 2011 persisted. RESEARCH DESIGN AND METHODS This longitudinal study followed 529,627 insulin-treated beneficiaries from 2009 through 2013 to assess changes in beneficiary acquisition of testing supplies in the initial nine test markets (TEST, n = 43,939) and beneficiaries not affected by the 2011 rollout (NONTEST, n = 485,688). All Medicare beneficiary records for analysis were obtained from CMS. RESULTS The percentages of beneficiaries with partial/no SMBG acquisition were significantly higher in both the TEST (37.4%) and NONTEST (37.6%) groups after the first 6 months of the national CBP rollout, showing increases of 48.1% and 60.0%, respectively (both P < 0.0001). The percentage of beneficiaries with no record for SMBG acquisition increased from 54.1% in January 2013 to 62.5% by December 2013. CONCLUSIONS Disruption of beneficiary access to their prescribed SMBG supplies has persisted and worsened. Diabetes testing supplies should be excluded from the CBP until transparent, science-based methodologies for safety monitoring are adopted and implemented.

    更新日期:2017-11-17
  • Declining Rates of Hospitalization for Selected Cardiovascular Disease Conditions Among Adults Aged ≥35 Years With Diagnosed Diabetes, U.S., 1998–2014
    Diabetes Care (IF 11.857) Pub Date : 2017-11-17
    Nilka Ríos Burrows; YanFeng Li; Edward W. Gregg; Linda S. Geiss

    OBJECTIVE Reductions in heart attack and stroke hospitalizations are well documented in the U.S. population with diabetes. We extended trend analyses to other cardiovascular disease (CVD) conditions, including stroke by type, and used four additional years of data. RESEARCH DESIGN AND METHODS Using 1998–2014 National (Nationwide) Inpatient Sample data, we estimated the number of discharges having acute coronary syndrome (ACS) (ICD-9 codes 410–411), cardiac dysrhythmia (427), heart failure (428), hemorrhagic stroke (430–432), or ischemic stroke (433.x1, 434, and 436) as first-listed diagnosis and diabetes (250) as secondary diagnosis. Hospitalization rates for adults aged ≥35 years were calculated using estimates from the population with and the population without diabetes from the National Health Interview Survey and age-adjusted to the 2000 U.S. standard population. Joinpoint regression was used to analyze trends and calculate an average annual percentage change (AAPC) with 95% confidence limits (CLs). RESULTS From 1998 to 2014, in the population with diabetes, age-adjusted hospitalization rates declined significantly for ACS (AAPC −4.6% per year [95% CL −5.3, −3.8]), cardiac dysrhythmia (−0.7% [−1.1, −0.2]), heart failure (−3.6% [−4.6, −2.7]), hemorrhagic stroke (−1.1% [−1.4, −0.7]), and ischemic stroke (−2.9% [−3.9, −1.8]). In the population without diabetes, rates also declined significantly for these conditions, with the exception of dysrhythmia. By 2014, rates in the population with diabetes population remained two to four times as high as those for the population without diabetes, with the largest difference in heart failure rates. CONCLUSIONS CVD hospitalization rates declined significantly in both the population with diabetes and the population without diabetes. This may be due to several factors, including new or more aggressive treatments and reductions in CVD risk factors and CVD incidence.

    更新日期:2017-11-17
  • N-Glycan Profile and Kidney Disease in Type 1 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-11-14
    Mairead L. Bermingham; Marco Colombo; Stuart J. McGurnaghan; Luke A.K. Blackbourn; Frano Vučković; Maja Pučić Baković; Irena Trbojević-Akmačić; Gordan Lauc; Felix Agakov; Anna S. Agakova; Caroline Hayward; Lucija Klarić; Colin N.A. Palmer; John R. Petrie; John Chalmers; Andrew Collier; Fiona Green; Robert S. Lindsay; Sandra Macrury; John A. McKnight; Alan W. Patrick; Sandeep Thekkepat; Olga Gornik; Paul M. McKeigue; Helen M. Colhoun

    OBJECTIVE Poorer glycemic control in type 1 diabetes may alter N-glycosylation patterns on circulating glycoproteins, and these alterations may be linked with diabetic kidney disease (DKD). We investigated associations between N-glycans and glycemic control and renal function in type 1 diabetes. RESEARCH DESIGN AND METHODS Using serum samples from 818 adults who were considered to have extreme annual loss in estimated glomerular filtration rate (eGFR; i.e., slope) based on retrospective clinical records, from among 6,127 adults in the Scottish Diabetes Research Network Type 1 Bioresource Study, we measured total and IgG-specific N-glycan profiles. This yielded a relative abundance of 39 total (GP) and 24 IgG (IGP) N-glycans. Linear regression models were used to investigate associations between N-glycan structures and HbA1c, albumin-to-creatinine ratio (ACR), and eGFR slope. Models were adjusted for age, sex, duration of type 1 diabetes, and total serum IgG. RESULTS Higher HbA1c was associated with a lower relative abundance of simple biantennary N-glycans and a higher relative abundance of more complex structures with more branching, galactosylation, and sialylation (GP12, 26, 31, 32, and 34, and IGP19 and 23; all P < 3.79 × 10−4). Similar patterns were seen for ACR and greater mean annual loss of eGFR, which were also associated with fewer of the simpler N-glycans (all P < 3.79 × 10−4). CONCLUSIONS Higher HbA1c in type 1 diabetes is associated with changes in the serum N-glycome that have elsewhere been shown to regulate the epidermal growth factor receptor and transforming growth factor-β pathways that are implicated in DKD. Furthermore, N-glycans are associated with ACR and eGFR slope. These data suggest that the role of altered N-glycans in DKD warrants further investigation.

    更新日期:2017-11-16
  • Incretin-Based Therapies and the Short-Term Risk of Pancreatic Cancer: Results From Two Retrospective Cohort Studies
    Diabetes Care (IF 11.857) Pub Date : 2017-11-10
    Mathieu Boniol; Matteo Franchi; Maria Bota; Agnès Leclercq; Joeri Guillaume; Nancy van Damme; Giovanni Corrao; Philippe Autier; Peter Boyle

    OBJECTIVE Concerns have been raised about a possible increased risk of pancreatic cancer associated with incretin-based therapies. We examined the risk of pancreatic cancer among patients with diabetes prescribed incretin drugs. RESEARCH DESIGN AND METHODS With the use of public health insurance databases of Belgium and Lombardy Region, Italy, we created two retrospective cohorts that included adult patients who were first prescribed an incretin drug or another noninsulin antidiabetic drug (NIAD) from 1 July 2008 to 31 December 2013 in Belgium and from 1 January 2008 to 31 December 2012 in Lombardy Region. The risk of pancreatic cancer was evaluated by multivariate-adjusted Cox models that included time-dependent variables. Adjusted hazard ratios (aHRs) from Belgium and Italy were pooled by using fixed-effects meta-analyses. RESULTS The cohorts included 525,733 patients with diabetes treated with NIADs and 33,292 with incretin drugs. Results in both cohorts were similar. Eighty-five and 1,589 subjects who developed pancreatic cancer were registered among the incretin and NIAD new users, respectively, which represented an aHR of pancreatic cancer of 2.14 (95% CI 1.71–2.67) among those prescribed an incretin compared with an NIAD. The aHR with a drug use lag exposure of 6 months was 1.69 (1.24–2.32). The aHR decreased from 3.35 (2.32–4.84) in the first 3 months after the first incretin prescription to 2.12 (1.22–3.66) in months 3–5.9, 1.95 (1.20–3.16) in months 6–11.9, and 1.69 (1.12–2.55) after 12 months. Among those prescribed an NIAD, pancreatic cancer occurred mostly within the year after the first prescription. The risk of pancreatic cancer among patients subsequently prescribed insulin was 6.89 (6.05–7.85). CONCLUSIONS The recent prescription of incretin therapy is associated with an increased risk of pancreatic cancer. The reason for such an increase is likely the consequence of an occult pancreatic cancer that provokes or aggravates diabetes. Studies are warranted for assessing the risk of pancreatic cancer associated with long-term use of incretin drugs.

    更新日期:2017-11-16
  • Disparities in Environmental Exposures to Endocrine-Disrupting Chemicals and Diabetes Risk in Vulnerable Populations
    Diabetes Care (IF 11.857) Pub Date : 2017-10-20
    Daniel Ruiz; Marisol Becerra; Jyotsna S. Jagai; Kerry Ard; Robert M. Sargis

    Burgeoning epidemiological, animal, and cellular data link environmental endocrine-disrupting chemicals (EDCs) to metabolic dysfunction. Disproportionate exposure to diabetes-associated EDCs may be an underappreciated contributor to disparities in metabolic disease risk. The burden of diabetes is not uniformly borne by American society; rather, this disease disproportionately affects certain populations, including African Americans, Latinos, and low-income individuals. The purpose of this study was to review the evidence linking unequal exposures to EDCs with racial, ethnic, and socioeconomic diabetes disparities in the U.S.; discuss social forces promoting these disparities; and explore potential interventions. Articles examining the links between chemical exposures and metabolic disease were extracted from the U.S. National Library of Medicine for the period of 1966 to 3 December 2016. EDCs associated with diabetes in the literature were then searched for evidence of racial, ethnic, and socioeconomic exposure disparities. Among Latinos, African Americans, and low-income individuals, numerous studies have reported significantly higher exposures to diabetogenic EDCs, including polychlorinated biphenyls, organochlorine pesticides, multiple chemical constituents of air pollution, bisphenol A, and phthalates. This review reveals that unequal exposure to EDCs may be a novel contributor to diabetes disparities. Efforts to reduce the individual and societal burden of diabetes should include educating clinicians on environmental exposures that may increase disease risk, strategies to reduce those exposures, and social policies to address environmental inequality as a novel source of diabetes disparities.

    更新日期:2017-11-15
  • The Role of Peers for Diabetes Management in Adolescents and Emerging Adults With Type 1 Diabetes: A Longitudinal Study
    Diabetes Care (IF 11.857) Pub Date : 2017-10-04
    Koen Raymaekers; Leen Oris; Sofie Prikken; Philip Moons; Eva Goossens; Ilse Weets; Koen Luyckx

    OBJECTIVE The increasing importance of peers in adolescence and emerging adulthood has been widely acknowledged. However, longitudinal research linking the peer context to diabetes management and outcomes is scarce. The present longitudinal study in a large sample of youths with type 1 diabetes related both positive and negative peer variables to diabetes outcomes over a time interval of 1 year. RESEARCH DESIGN AND METHODS Our sample consisted of 467 adolescents (14–17 years of age) and emerging adults (18–25 years of age) with type 1 diabetes who participated in a two-wave longitudinal study. Questionnaires tapped into peer support, extreme peer orientation, parental responsiveness, diabetes-related distress, and treatment adherence. HbA1c values were obtained from the treating physicians of patients. Cross-lagged analysis from a structural equation modeling approach was performed to assess the directionality of effects. RESULTS Peer support negatively predicted diabetes-related distress over time. Extreme peer orientation positively predicted treatment distress over time. Parental responsiveness negatively predicted food distress over time. Treatment adherence negatively predicted extreme peer orientation, treatment distress, and HbA1c values over time. For emerging adults specifically, there was a reciprocal relationship between HbA1c values and extreme peer orientation, because they positively predicted each other. CONCLUSIONS This study highlights the importance of peers in predicting the functioning of youths with type 1 diabetes. Additionally, treatment adherence at baseline was found to negatively predict extreme peer orientation, treatment distress, and worse glycemic control over time. In sum, the current study underscores the importance of the peer context for adolescents and emerging adults with type 1 diabetes.

    更新日期:2017-11-15
  • Five-Year Effectiveness of the Multidisciplinary Risk Assessment and Management Program for Primary Care Patients With Type 2 Diabetes Mellitus‎ (RAMP-DM) on DM-Related Complications and Health Service Uses—A Population-Based and Propensity-Matched Cohort Study
    Diabetes Care (IF 11.857) Pub Date : 2017-10-24
    Eric Yuk Fai Wan; Colman Siu Cheung Fung; Fang Fang Jiao; Esther Yee Tak Yu; Weng Yee Chin; Daniel Yee Tak Fong; Carlos King Ho Wong; Anca Ka Chun Chan; Karina Hiu Yen Chan; Ruby Lai Ping Kwok; Cindy Lo Kuen Lam

    OBJECTIVE To evaluate the 5-year effectiveness of a multidisciplinary Risk Assessment and Management Program for primary care patients with type 2 Diabetes Mellitus (RAMP-DM)‎. RESEARCH DESIGN AND METHODS A 5-year prospective cohort study was conducted with 121,584 Chinese primary care patients with type 2 DM who were recruited between August 2009 and June 2011. Missing data were dealt with multiple imputations. After excluding patients with prior DM-related complications and one-to-one propensity score matching on all patient characteristics, 26,718 RAMP-DM participants and 26,718 matched usual-care patients were followed up for a median time of 4.5 years. The effect of RAMP-DM on nine DM-related complications and all-cause mortality were evaluated using Cox regressions. The first incidence for each event was used for all models. Health service use was analyzed using negative binomial regressions. Subgroup analyses on different patient characteristics were performed. RESULTS The cumulative incidence of all events (DM-related complications and all-cause mortality) was 23.2% in the RAMP-DM group and 43.6% in the usual-care group. RAMP-DM led to significantly greater reductions in cardiovascular disease (CVD) risk by 56.6% (95% CI 54.5, 58.6%); microvascular complications by 11.9% (95% CI 7.0, 16.6%); mortality by 66.1% (95% CI 64.3, 67.9%); specialist attendance by 35.0% (95% CI 33.6, 36.4%); emergency attendance by 41.2% (95% CI 39.8, 42.5%); and hospitalizations by 58.5% (95% CI 57.2, 59.7%). Patients with low baseline CVD risks benefitted the most from RAMP-DM, which decreased CVD and mortality risk by 60.4% (95% CI 51.8, 67.5%) and 83.6% (95% CI 79.3, 87.0%), respectively. CONCLUSIONS This naturalistic study highlighted the importance of early optimal DM control and risk factor management by risk stratification and multidisciplinary, protocol-driven, chronic disease model care to delay disease progression and prevent complications.

    更新日期:2017-11-15
  • Enhanced Predictive Capability of a 1-Hour Oral Glucose Tolerance Test: A Prospective Population-Based Cohort Study
    Diabetes Care (IF 11.857) Pub Date : 2017-10-25
    Manan Pareek; Deepak L. Bhatt; Mette L. Nielsen; Ram Jagannathan; Karl-Fredrik Eriksson; Peter M. Nilsson; Michael Bergman; Michael H. Olsen

    OBJECTIVE To examine whether the 1-h blood glucose measurement would be a more suitable screening tool for assessing the risk of diabetes and its complications than the 2-h measurement. RESEARCH DESIGN AND METHODS We conducted a prospective population-based cohort study of 4,867 men, randomly selected from prespecified birth cohorts between 1921 and 1949, who underwent an oral glucose tolerance test with blood glucose measurements at 0, 1, and 2 h. Subjects were followed for up to 39 years, with registry-based recording of events. Discriminative abilities of elevated 1-h (≥8.6 mmol/L) versus 2-h (≥7.8 mmol/L) glucose for predicting incident type 2 diabetes, vascular complications, and mortality were compared using Kaplan-Meier analysis, Cox proportional hazards regression, and net reclassification improvement. RESULTS Median age was 48 years (interquartile range [IQR] 48–49). During follow-up (median 33 years [IQR 24–37]), 636 (13%) developed type 2 diabetes. Elevated 1-h glucose was associated with incident diabetes (hazard ratio 3.40 [95% CI 2.90–3.98], P < 0.001) and provided better risk assessment than impaired glucose tolerance (C index 0.637 vs. 0.511, P < 0.001). Addition of a 1-h measurement in subjects stratified by fasting glucose provided greater net reclassification improvement than the addition of a 2-h measurement (0.214 vs. 0.016, respectively). Finally, the 1-h glucose was significantly associated with vascular complications and mortality. CONCLUSIONS The 1-h blood glucose level is a stronger predictor of future type 2 diabetes than the 2-h level and is associated with diabetes complications and mortality.

    更新日期:2017-11-15
  • Impact of Excessive Weight Gain on Cardiovascular Outcomes in Type 1 Diabetes: Results From the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study
    Diabetes Care (IF 11.857) Pub Date : 2017-10-25
    Jonathan Q. Purnell; Barbara H. Braffett; Bernard Zinman; Rose A. Gubitosi-Klug; William Sivitz; John P. Bantle; Georgia Ziegler; Patricia A. Cleary; John D. Brunzell; the DCCT/EDIC Research Group

    OBJECTIVE Intensive treatment (INT) of type 1 diabetes reduces the incidence of cardiovascular disease (CVD) events compared with conventional treatment (CONV), but it also results in more weight gain. Our objective was to examine whether excessive weight gain from INT of type 1 diabetes is independently associated with subsequent CVD events. RESEARCH DESIGN AND METHODS Quartiles (Q) of weight gain in 1,213 participants aged 18 years and older at enrollment in the Diabetes Control and Complications Trial (DCCT) were determined within randomized treatment groups (INT vs. CONV) using change in BMI from baseline to the closeout DCCT visits. Effects of this weight gain on CVD risk factors and outcomes during an additional 20 years of observational follow-up were then determined. RESULTS The Q4 INT group experienced greater proportional weight gain (median change in BMI, 6.08 kg/m2), increases in CVD risk factors, and need for medications for hypertension and lipids compared with the Q1–3 INT and comparable CONV groups. Over a mean of 26 years of follow-up, the numbers of major and total CVD events were not statistically different in Q4 compared with Q1–3 of either the INT or CONV group. By year 14, however, the incident CVD event curve became significantly higher in the Q4 INT group than in the Q1–3 INT groups (P = 0.024) and was similar to that for the CONV group. CONCLUSIONS For the first 13 years after DCCT, INT for type 1 diabetes reduced macrovascular events compared with CONV, even when excessive weight gain occurred. After this, total CVD events significantly increased in the Q4 INT group, becoming equivalent to those in the CONV group. Longer follow-up is needed to determine whether this trend continues and results in more major CVD events.

    更新日期:2017-11-15
  • Clinical and Histologic Characterization of Nonalcoholic Steatohepatitis in African American Patients
    Diabetes Care (IF 11.857) Pub Date : 2017-11-10
    Fernando Bril; Paola Portillo-Sanchez; I-Chia Liu; Srilaxmi Kalavalapalli; Kristin Dayton; Kenneth Cusi

    OBJECTIVE There has been a widespread misconception among physicians that African Americans are protected from developing nonalcoholic steatohepatitis (NASH). However, a formal histologic and metabolic comparison against well-matched Caucasians has never been performed. RESEARCH DESIGN AND METHODS Sixty-seven African American patients were matched 2:1 to Caucasians (n = 134) for age, sex, BMI, hemoglobin A1c, and prevalence of type 2 diabetes mellitus (T2DM). Screening for NASH included measurement of intrahepatic triglyceride content by proton MRS (1H-MRS), followed by a liver biopsy if patients had hepatic steatosis. Insulin resistance was estimated during an oral glucose tolerance test using the Matsuda Index. RESULTS Compared with Caucasians, African American patients had a lower intrahepatic triglyceride content ([mean ± SD] 6.1 ± 6.8% vs. 9.4 ± 7.5%, P = 0.007) and the presence of nonalcoholic fatty liver disease (NAFLD) was less common (25.0% vs. 51.9%, P = 0.003). However, prevalence of NASH was not different between ethnicities in patients with NAFLD (57.1% vs. 73.3%, P = 0.12). Moreover, they showed similar severity in each of the individual histological parameters (inflammation, ballooning, and fibrosis). Among patients with NAFLD, insulin resistance was similar between both ethnic groups (Matsuda Index: 3.3 ± 1.8 vs. 3.1 ± 1.9, P = 0.61; adipose tissue insulin resistance [Adipo-IR] index: 5.7 ± 4.6 vs. 6.4 ± 4.7 mmol/L ⋅ µU/mL, P = 0.53) but appeared to be worse in African American versus Caucasian patients without NAFLD (Matsuda Index: 4.9 ± 3.6 vs. 7.0 ± 4.9 P = 0.11; Adipo-IR: 3.9 ± 2.8 vs. 2.7 ± 2.3 mmol/L ⋅ µU/mL, P = 0.06). African American patients also had lower plasma triglycerides and higher HDL cholesterol, independent of the severity of intrahepatic triglyceride. CONCLUSIONS Although African Americans have lower intrahepatic triglyceride accumulation, once NAFLD develops, NASH occurs as frequently, and as severe, as in Caucasian patients. Therefore, African Americans with NAFLD should be screened for NASH with the same degree of clinical resolve as in Caucasian patients.

    更新日期:2017-11-13
  • The Association of Severe Hypoglycemia With Incident Cardiovascular Events and Mortality in Adults With Type 2 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-11-06
    Alexandra K. Lee; Bethany Warren; Clare J. Lee; John W. McEvoy; Kunihiro Matsushita; Elbert S. Huang; A. Richey Sharrett; Josef Coresh; Elizabeth Selvin

    OBJECTIVE There is suggestive evidence linking hypoglycemia with cardiovascular disease, but few data have been collected in a community-based setting. Information is lacking on individual cardiovascular outcomes and cause-specific mortality. RESEARCH DESIGN AND METHODS We conducted a prospective cohort analysis of 1,209 participants with diagnosed diabetes from the Atherosclerosis Risk in Communities (ARIC) Study (analytic baseline, 1996–1998). Severe hypoglycemic episodes were identified using first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls through 2013. Cardiovascular events and deaths were captured through 2013. We used adjusted Cox regression models with hypoglycemia as a time-varying exposure. RESULTS There were 195 participants with at least one severe hypoglycemic episode during a median fellow-up of 15.3 years. After severe hypoglycemia, the 3-year cumulative incidence of coronary heart disease was 10.8% and of mortality was 28.3%. After adjustment, severe hypoglycemia was associated with coronary heart disease (hazard ratio [HR] 2.02, 95% CI 1.27–3.20), all-cause mortality (HR 1.73, 95% CI 1.38–2.17), cardiovascular mortality (HR 1.64, 95% CI 1.15–2.34), and cancer mortality (HR 2.49, 95% CI 1.46–4.24). Hypoglycemia was not associated with stroke, heart failure, atrial fibrillation, or noncardiovascular and noncancer death. Results were robust within subgroups defined by age, sex, race, diabetes duration, and baseline cardiovascular risk. CONCLUSIONS Severe hypoglycemia is clearly indicative of declining health and is a potent marker of high absolute risk of cardiovascular events and mortality.

    更新日期:2017-11-11
  • 2017 National Standards for Diabetes Self-Management Education and Support
    Diabetes Care (IF 11.857) Pub Date : 2017-10-01
    Joni Beck; Deborah A. Greenwood; Lori Blanton; Sandra T. Bollinger; Marcene K. Butcher; Jo Ellen Condon; Marjorie Cypress; Priscilla Faulkner; Amy Hess Fischl; Theresa Francis; Leslie E. Kolb; Jodi M. Lavin-Tompkins; Janice MacLeod; Melinda Maryniuk; Carolé Mensing; Eric A. Orzeck; David D. Pope; Jodi L. Pulizzi; Ardis A. Reed; Andrew S. Rhinehart; Linda Siminerio; Jing Wang

    By the most recent estimates, 30.3 million people in the U.S. have diabetes. An estimated 23.1 million have been diagnosed with diabetes and 7.2 million are believed to be living with undiagnosed diabetes. At the same time, 84.1 million people are at increased risk for type 2 diabetes. Thus, more than 114 million Americans are at risk for developing the devastating complications of diabetes (1).Diabetes self-management education and support (DSMES) is a critical element of care for all people with diabetes. DSMES is the ongoing process of facilitating the knowledge, skills, and ability necessary for diabetes self-care, as well as activities that assist a person in implementing and sustaining the behaviors needed to manage his or her condition on an ongoing basis, beyond or outside of formal self-management training. In previous National Standards for Diabetes Self-Management Education and Support (Standards), DSMS and DSME were defined separately, but these Standards aim to reflect the value of ongoing support and multiple services.The Standards define timely, evidence-based, quality DSMES services that meet or exceed the Medicare diabetes self-management training (DSMT) regulations, however, these Standards do not guarantee reimbursement. These Standards provide evidence for all diabetes self-management education providers including those that do not plan to seek reimbursement for DSMES. The current Standards’ evidence clearly identifies the need to provide person-centered services that embrace the ever-increasing technological engagement platforms and systems. The hope is that payers will view these Standards as a tool for reviewing DSMES reimbursement requirements and consider change to align with the way their beneficiaries’ engagement preferences have evolved. Research confirms that less than 5% of Medicare beneficiaries utilize their DSMES benefits (2,3). Changes in reimbursement policies stand to increase DSMES access and utilization, which will result in positive impact to beneficiaries’ clinical outcomes, quality of …

    更新日期:2017-11-10
  • 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:2017-11-10
  • 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:2017-11-10
  • Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-11-07
    Clare B. Kelly; Michelle B. Hookham; Jeremy Y. Yu; Alicia J. Jenkins; Alison J. Nankervis; Kristian F. Hanssen; Satish K. Garg; James A. Scardo; Samar M. Hammad; M. Kathryn Menard; Christopher E. Aston; Timothy J. Lyons

    OBJECTIVE This study was conducted to determine the utility of tubular (urinary/plasma neutrophil gelatinase-associated lipocalin [NGAL] and urinary kidney injury molecule 1 [KIM-1]) and glomerular (estimated glomerular filtration rate [eGFR]) biomarkers in predicting preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM) who were free of microalbuminuria and hypertension at the first trimester. RESEARCH DESIGN AND METHODS This was a prospective study of T1DM pregnancy. Maternal urinary and plasma NGAL urinary KIM-1 (ELISA of frozen samples), and eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) were determined at three study visits (V1: 12.4 ± 1.8; V2: 21.7 ± 1.4; V3: 31.4 ± 1.5 weeks’ gestation [mean ± SD]) in 23 women with T1DM with subsequent PE (DM+PE+), 24 who remained normotensive (DM+PE−), and, for reference, in 19 normotensive pregnant women without diabetes (DM−). The groups with diabetes were matched for age, diabetes duration, HbA1c, and parity. All subjects were normotensive and free of microalbuminuria or albuminuria at V1. All study visits preceded the onset of PE. RESULTS Urinary creatinine-corrected NGAL (uNGALcc, ng/mg) was significantly elevated at V1 in DM+PE+ versus DM+PE− women (P = 0.01); this remained significant after exclusion of leukocyte-positive samples (5 DM+PE+ and 2 DM+PE−) (P = 0.02). Accounting for BMI, HbA1c, and total daily insulin dose, a doubling of uNGALcc at V1 conferred a sevenfold increase in risk for PE (P = 0.026). In contrast, neither plasma NGAL nor urinary KIM-1 predicted PE. Also at V1, eGFR was elevated in DM+PE+ versus DM+PE− (P = 0.04). CONCLUSIONS Early tubular and glomerular dysfunction may predict PE in first trimester women with T1DM, even if free of microalbuminuria. These data suggest that subclinical renal tubular and glomerular injury, if present early in pregnancy, may predispose women with T1DM to PE.

    更新日期:2017-11-09
  • Prospective Postmarketing Surveillance of Acute Myocardial Infarction in New Users of Saxagliptin: A Population-Based Study
    Diabetes Care (IF 11.857) Pub Date : 2017-11-09
    Sengwee Toh; Marsha E. Reichman; David J. Graham; Christian Hampp; Rongmei Zhang; Melissa G. Butler; Aarthi Iyer; Malcolm Rucker; Madelyn Pimentel; Jack Hamilton; Samuel Lendle; Bruce H. Fireman; for the Mini-Sentinel Saxagliptin-AMI Surveillance Writing Group

    OBJECTIVE The cardiovascular safety of saxagliptin, a dipeptidyl-peptidase 4 inhibitor, compared with other antihyperglycemic treatments is not well understood. We prospectively examined the association between saxagliptin use and acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS We identified patients aged ≥18 years, starting from the approval date of saxagliptin in 2009 and continuing through August 2014, using data from 18 Mini-Sentinel data partners. We conducted seven sequential assessments comparing saxagliptin separately with sitagliptin, pioglitazone, second-generation sulfonylureas, and long-acting insulin, using disease risk score (DRS) stratification and propensity score (PS) matching to adjust for potential confounders. Sequential testing kept the overall chance of a false-positive signal below 0.05 (one-sided) for each pairwise comparison. RESULTS We identified 82,264 saxagliptin users and more than 1.5 times as many users of each comparator. At the end of surveillance, the DRS-stratified hazard ratios (HRs) (95% CI) were 1.08 (0.90–1.28) in the comparison with sitagliptin, 1.11 (0.87–1.42) with pioglitazone, 0.79 (0.64–0.98) with sulfonylureas, and 0.57 (0.46–0.70) with long-acting insulin. The corresponding PS-matched HRs were similar. Only one interim analysis of 168 analyses met criteria for a safety signal: the PS-matched saxagliptin-pioglitazone comparison from the fifth sequential analysis, which yielded an HR of 1.63 (1.12–2.37). This association diminished in subsequent analyses. CONCLUSIONS We did not find a higher AMI risk in saxagliptin users compared with users of other selected antihyperglycemic agents during the first 5 years after U.S. Food and Drug Administration approval of the drug.

    更新日期:2017-11-09
  • Association Between Inflammatory Markers and Progression to Kidney Dysfunction: Examining Different Assessment Windows in Patients With Type 1 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-11-06
    Nathaniel L. Baker; Kelly J. Hunt; Danielle R. Stevens; Gabor Jarai; Glenn D. Rosen; Richard L. Klein; Gabriel Virella; Maria F. Lopes-Virella; the DCCT/EDIC Research Group

    OBJECTIVE To determine whether biomarkers of inflammation and endothelial dysfunction are associated with the development of kidney dysfunction and the time frame of their association. RESEARCH DESIGN AND METHODS Biomarkers were measured at four time points during 28 years of treatment and follow-up in patients with type 1 diabetes in the DCCT/EDIC cohort. In addition to traditional biomarkers of inflammation (C-reactive protein and fibrinogen), we measured interleukin-6 (IL-6) and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1/2), markers of endothelial dysfunction (soluble intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin [sE-selectin]), and fibrinolysis (total and active plasminogen activator inhibitor-1 [PAI-1]). Renal outcomes were defined as progression to incident chronic kidney disease (stage 3 or more severe) or macroalbuminuria (albumin excretion rate ≥300 mg/24 h). Prospective multivariate event-time analyses were used to determine the association of each biomarker with each subsequent event within prespecified intervals (3-year and 10-year windows). RESULTS Multivariate event-time models indicated that several markers of inflammation (sTNFR-1/2), endothelial dysfunction (sE-selectin), and clotting/fibrinolysis (fibrinogen and PAI-1) are significantly associated with subsequent development of kidney dysfunction. Although some markers showed variations in the associations between the follow-up windows examined, the results indicate that biomarkers (sTNFR-1/2, sE-selectin, PAI-1, and fibrinogen) are associated with progression to chronic kidney disease in both the 3-year and the 10-year windows. CONCLUSIONS Plasma markers of inflammation, endothelial dysfunction, and clotting/fibrinolysis are associated with progression to kidney dysfunction in type 1 diabetes during both short-term and long-term follow-up.

    更新日期:2017-11-08
  • Diabetes Care Disparities in Long-standing Type 1 Diabetes in Canada and the United States: A Cross-Sectional Comparison
    Diabetes Care (IF 11.857) Pub Date : 2017-11-06
    Alanna Weisman; Leif E. Lovblom; Hillary A. Keenan; Liane J. Tinsley; Stephanie D’Eon; Genevieve Boulet; Mohammed A. Farooqi; Julie A. Lovshin; Andrej Orszag; Yuliya Lytvyn; Michael H. Brent; Narinder Paul; Vera Bril; David Z. Cherney; Bruce A. Perkins

    OBJECTIVE To assess national differences in diabetes care and quality of life (QOL) between individuals with long-standing type 1 diabetes (≥50 years) in Canada and the U.S. RESEARCH DESIGN AND METHODS Cross-sectional data from identical surveys administered in the Canadian Study of Longevity in Diabetes and the Joslin Medalist Study, collected in 2013–2016 and 2005–2011, respectively, were compared. Laboratory values and ophthalmic examination were completed by clinical care physicians for Canadians and the Joslin Clinic for Americans. Univariate comparisons and multivariable regression for HbA1c, QOL, insulin pump use, and coronary artery disease (CAD) were performed. Nephropathy, CAD, and peripheral arterial disease (PAD) were self-reported; neuropathy was defined by a Michigan Neuropathy Screening Instrument (Questionnaire component) score ≥3, and proliferative retinopathy was documented from ophthalmic examination. QOL was self-reported on an ordinal scale. RESULTS Three hundred sixty-one Canadians and 668 Americans had similar ages (mean 65.78 years [SD 8.67 years] vs. 66.38 years [7.66 years], P = 0.27) and durations of diabetes (median 53.00 years [interquartile range 51.00, 58.00 years] vs. 53.00 years [51.00, 57.00 years], P = 0.51). Canadians had higher HbA1c (mean 7.53% [SD 1.03% (59 mmol/mol)] vs. 7.22% [0.98% (55 mmol/mol)], P < 0.0001), lower QOL (36.9% vs. 48.7% with “excellent” QOL, P = 0.0002), and less CAD (29.7% vs. 41.2%, P = 0.0003), and insulin pump use (43.3% vs. 55.6%, P = 0.0002). Other complication rates were similar. Residual differences for Canadians compared with Americans remained after adjustment for age, sex, CAD, PAD, education, and relevant a priori selected variables: 0.28% higher HbA1c (P = 0.0004); and odds ratios of 0.68 (95% CI 0.51–0.90), 0.46 (0.31–0.68), and 0.71 (0.52–0.96) for higher QOL, CAD, and insulin pump use, respectively. CONCLUSIONS Although Canadians and Americans have similar rates of complications other than CAD, further research is required to understand why Canadians have higher HbA1c levels, lower QOL, and less insulin pump use.

    更新日期:2017-11-08
  • FGF23 Concentration and APOL1 Genotype Are Novel Predictors of Mortality in African Americans With Type 2 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-11-06
    Gary C. Chan; Jasmin Divers; Gregory B. Russell; Carl D. Langefeld; Lynne E. Wagenknecht; Fang-Chi Hsu; Jianzhao Xu; S. Carrie Smith; Nicholette D. Palmer; Pamela J. Hicks; Donald W. Bowden; Thomas C. Register; Lijun Ma; J. Jeffrey Carr; Barry I. Freedman

    OBJECTIVE Cardiovascular and renal complications contribute to higher mortality in patients with diabetes. We assessed novel and conventional predictors of mortality in African American–Diabetes Heart Study participants. RESEARCH DESIGN AND METHODS Associations between mortality and subclinical atherosclerosis, urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), plasma fibroblast growth factor 23 (FGF23) concentration, African ancestry proportion, and apolipoprotein L1 genotypes (APOL1) were assessed in 513 African Americans with type 2 diabetes; analyses were performed using Cox proportional hazards models. RESULTS At baseline, participants were 55.6% female with median (25th, 75th percentile) age 55 years (49.0, 62.0), diabetes duration 8 years (5.0, 13.0), glycosylated hemoglobin 60.7 mmol/mol (48.6, 76.0), eGFR 91.3 mL/min/1.73 m2 (76.4, 111.3), UACR 12.5 mg/mmol (4.2, 51.2), and coronary artery calcium 28.5 mg Ca2+ (1.0, 348.6); 11.5% had two APOL1 renal-risk variants. After 6.6-year follow-up (5.8, 7.5), 54 deaths were recorded. Higher levels of coronary artery calcified plaque, carotid artery calcified plaque, albuminuria, and FGF23 were associated with higher mortality after adjustment for age, sex, and African ancestry proportion. A penalized Cox regression that included all covariates and predictors associated with mortality identified male sex (hazard ratio [HR] 4.17 [95% CI 1.96–9.09]), higher FGF23 (HR 2.10 [95% CI 1.59–2.78]), and absence of APOL1 renal-risk genotypes (HR 0.07 [95% CI 0.01–0.69]) as the strongest predictors of mortality. CONCLUSIONS Accounting for conventional risk factors, higher FGF23 concentrations and APOL1 non–renal-risk genotypes associated with higher mortality in African Americans with diabetes. These data add to growing evidence supporting FGF23 association with mortality; mechanisms whereby these novel predictors impact survival remain to be determined.

    更新日期:2017-11-07
  • Cardiovascular Complications Over 5 Years, and Their Association With Survival in the GERODIAB Cohort of Elderly French Patients With Type 2 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-11-06
    Bernard Bauduceau; Jean-Pierre Le Floch; Serge Halimi; Christiane Verny; Jean Doucet; the SFD/SFGG Intergroup

    OBJECTIVE The GERODIAB study is a multicenter prospective observational study performed over 5 years in French patients aged 70 years or above with type 2 diabetes. This report deals with their cardiovascular complications and their relationship with survival. RESEARCH DESIGN AND METHODS Consecutive patients (n = 987, median age = 77 years) were included from 56 diabetes centers over 1 year. Individual characteristics, history and complications of diabetes, geriatric factors, and clinical and biological parameters were recorded. Survival was analyzed using the Kaplan-Meier method and proportional hazards regression models. RESULTS The frequency of cardiovascular complications increased from 47% at inclusion to 67% at 5 years. The most frequent complications were coronary heart disease (increasing from 30% to 41%) and vascular disease of the lower limbs (25% to 35%) and of the cerebral vessels (15% to 26%). Heart failure was less common, but its frequency doubled during the follow-up (9% to 20%). It was strongly associated with poor survival (P < 0.0001), as was vascular disease of the lower limbs (P = 0.0004), whereas coronary heart disease (P = 0.0056) and vascular disease of cerebral vessels (P = 0.026) had mild associations. Amputation (P < 0.0001) and foot wounds (P < 0.0001) were strongly associated with survival. In multivariate models, heart failure was the strongest predictor of poor survival (hazard ratio [HR] 1.96 [95% CI 1.45–2.64]; P < 0.0001). It remained significant when other factors were considered simultaneously (HR 1.92 [95% CI 1.43–2.58]; P < 0.0001). CONCLUSIONS Cardiovascular complications are associated with poor survival in elderly patients with type 2 diabetes, especially heart failure.

    更新日期:2017-11-07
  • Long-term Trends in Antidiabetes Drug Usage in the U.S.: Real-world Evidence in Patients Newly Diagnosed With Type 2 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-11-06
    Olga Montvida; Jonathan Shaw; John J. Atherton; Frances Stringer; Sanjoy K. Paul

    OJBECTIVE To explore temporal trends in antidiabetes drug (ADD) prescribing and intensification patterns, along with glycemic levels and comorbidities, and possible benefits of novel ADDs in delaying the need for insulin initiation in patients diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes aged 18–80 years, who initiated any ADD, were selected (n = 1,023,340) from the U.S. Centricity Electronic Medical Records. Those who initiated second-line ADD after first-line metformin were identified (subcohort 1, n = 357,482); the third-line therapy choices were further explored. RESULTS From 2005 to 2016, first-line use increased for metformin (60–77%) and decreased for sulfonylureas (20–8%). During a mean follow-up of 3.4 years post metformin, 48% initiated a second ADD at a mean HbA1c of 8.4%. In subcohort 1, although sulfonylurea usage as second-line treatment decreased (60–46%), it remained the most popular second ADD choice. Use increased for insulin (7–17%) and dipeptidyl peptidase-4 inhibitors (DPP-4i) (0.4–21%). The rates of intensification with insulin and sulfonylureas did not decline over the last 10 years. The restricted mean time to insulin initiation was marginally longer in second-line DPP-4i (7.1 years) and in the glucagon-like peptide 1 receptor agonist (6.6 years) group compared with sulfonylurea (6.3 years, P < 0.05). CONCLUSIONS Most patients initiate second-line therapy at elevated HbA1c levels, with highly heterogeneous clinical characteristics across ADD classes. Despite the introduction of newer therapies, sulfonylureas remained the most popular second-line agent, and the rates of intensification with sulfonylureas and insulin remained consistent over time. The incretin-based therapies were associated with a small delay in the need for therapy intensification compared with sulfonylureas.

    更新日期:2017-11-06
  • Severity of Neuropathy Is Associated With Long-Term Spinal Cord Stimulation Outcome in Painful Diabetic Peripheral Neuropathy: Five-Year Follow-up of a Prospective Two-Center Clinical Trial
    Diabetes Care (IF 11.857) Pub Date : 2017-11-06
    Maarten van Beek; José W. Geurts; Rachel Slangen; Nicolaas C. Schaper; Catharina G. Faber; Elbert A. Joosten; Carmen D. Dirksen; Robert T. van Dongen; Sander M.J. van Kuijk; Maarten van Kleef

    OBJECTIVE Evidence from prospective studies for long-term treatment efficacy of spinal cord stimulation (SCS) in painful diabetic polyneuropathy (PDPN) is not available. We report prospective data on the effect of SCS on pain ratings, treatment success and failure, and complications during a 5-year follow-up in patients with PDPN. RESEARCH DESIGN AND METHODS Patients with PDPN (n = 48) were included in this prospective multicenter study. The Michigan Diabetic Neuropathy Score (MDNS) was used to assess the severity of neuropathy. Numerical rating scale (NRS) score for pain, Patient’s Global Impression of Change (PGIC), and treatment success (50% reduction of NRS score or significant PGIC) during 5 years of follow-up were evaluated. Complications of SCS were reported, and associations between baseline characteristics and SCS trial success or failure during a 5-year follow-up were investigated by using survival analyses. RESULTS Treatment success was observed in 55% of patients after 5 years. Median duration of SCS treatment was 60 months (minimum 1 month, maximum 60 months), and 80% of patients with a permanent implant still used their SCS device after 5 years. Higher MDNS was associated with treatment failure during the 5-year follow-up (hazard ratio 3.9 [95% CI 1.3–11.6]; P = 0.014). CONCLUSIONS SCS is successful in reducing chronic pain symptoms in the lower extremities of patients with PDPN up to 5 years after initiation of treatment. Furthermore, 80% of patients with PDPN still use their SCS device after 5 years. Moreover, the severity of neuropathy is associated with a higher chance of long-term treatment failure during a 5-year follow-up.

    更新日期:2017-11-06
  • Changes in Albuminuria and the Risk of Major Clinical Outcomes in Diabetes: Results From ADVANCE-ON
    Diabetes Care (IF 11.857) Pub Date : 2017-10-25
    Min Jun; Toshiaki Ohkuma; Sophia Zoungas; Stephen Colagiuri; Giuseppe Mancia; Michel Marre; David Matthews; Neil Poulter; Bryan Williams; Anthony Rodgers; Vlado Perkovic; John Chalmers; Mark Woodward

    OBJECTIVE To assess the association between 2-year changes in urine albumin-to-creatinine ratio (UACR) and the risk of clinical outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS We analyzed data from 8,766 participants in the ADVANCE-ON study. Change in UACR was calculated from UACR measurements 2 years apart, classified into three groups: decrease in UACR of ≥30%, minor change, and increase in UACR of ≥30%. By analyzing changes from baseline UACR groups, categorized into thirds, we repeated these analyses accounting for regression to the mean (RtM). The primary outcome was the composite of major macrovascular events, renal events, and all-cause mortality; secondary outcomes were these components. Cox regression models were used to estimate hazard ratios (HRs). RESULTS Over a median follow-up of 7.7 years, 2,191 primary outcomes were observed. Increases in UACR over 2 years independently predicted a greater risk of the primary outcome (HR for ≥30% UACR increase vs. minor change: 1.26; 95% CI 1.13–1.41), whereas a decrease in UACR was not significantly associated with lower risk (HR 0.93; 95% CI 0.83–1.04). However, after allowing for RtM, the effect of “real” decrease in UACR on the primary outcome was found to be significant (HR 0.84; 95% CI 0.75–0.94), whereas the estimated effect on an increase was unchanged. CONCLUSIONS Changes in UACR predicted changes in the risk of major clinical outcomes and mortality in type 2 diabetes, supporting the prognostic utility of monitoring albuminuria change over time.

    更新日期:2017-10-27
  • Prediction of Type 2 Diabetes by Hemoglobin A1c in Two Community-Based Cohorts
    Diabetes Care (IF 11.857) Pub Date : 2017-10-25
    Aaron Leong; Natalie Daya; Bianca Porneala; James J. Devlin; Dov Shiffman; Michael J. McPhaul; Elizabeth Selvin; James B. Meigs

    OBJECTIVE Hemoglobin A1c (HbA1c) can be used to assess type 2 diabetes (T2D) risk. We asked whether HbA1c was associated with T2D risk in four scenarios of clinical information availability: 1) HbA1c alone, 2) fasting laboratory tests, 3) clinic data, and 4) fasting laboratory tests and clinic data. RESEARCH DESIGN AND METHODS We studied a prospective cohort of white (N = 11,244) and black (N = 2,294) middle-aged participants without diabetes in the Framingham Heart Study and Atherosclerosis Risk in Communities study. Association of HbA1c with incident T2D (defined by medication use or fasting glucose [FG] ≥126 mg/dL) was evaluated in regression models adjusted for 1) age and sex (demographics); 2) demographics, FG, HDL, and triglycerides; 3) demographics, BMI, blood pressure, and T2D family history; or 4) all preceding covariates. We combined results from cohort and race analyses by random-effects meta-analyses. Subsidiary analyses tested the association of HbA1c with developing T2D within 8 years or only after 8 years. RESULTS Over 20 years, 3,315 individuals developed T2D. With adjustment for demographics, the odds of T2D increased fourfold for each percentage-unit increase in HbA1c. The odds ratio (OR) was 4.00 (95% CI 3.14, 5.10) for blacks and 4.73 (3.10, 7.21) for whites, resulting in a combined OR of 4.50 (3.35, 6.03). After adjustment for fasting laboratory tests and clinic data, the combined OR was 2.68 (2.15, 3.34) over 20 years, 5.79 (2.51, 13.36) within 8 years, and 2.23 (1.94, 2.57) after 8 years. CONCLUSIONS HbA1c predicts T2D in different common scenarios and is useful for identifying individuals with elevated T2D risk in both the short- and long-term.

    更新日期:2017-10-27
  • Physical Activity Reduces Risk of Premature Mortality in Patients With Type 1 Diabetes With and Without Kidney Disease
    Diabetes Care (IF 11.857) Pub Date : 2017-10-13
    Heidi Tikkanen-Dolenc; Johan Wadén; Carol Forsblom; Valma Harjutsalo; Lena M. Thorn; Markku Saraheimo; Nina Elonen; Heikki O. Tikkanen; Per-Henrik Groop

    OBJECTIVE The aims of the study were to assess how baseline leisure-time physical activity (LTPA) and its exercise components intensity, duration, and frequency are associated with all-cause and cardiovascular mortality in patients with type 1 diabetes 1) overall, 2) stratified by presence or absence of chronic kidney disease (CKD), and 3) stratified by sex. RESEARCH DESIGN AND METHODS The study design was prospective and observational and included 2,639 patients with type 1 diabetes from the ongoing nationwide multicenter Finnish Diabetic Nephropathy (FinnDiane) Study. Mean follow-up time was 11.4 ± 3.5 years. LTPA was assessed by using a validated self-report questionnaire. Three hundred ten patients (11.7%) had CKD defined as an estimated glomerular filtration rate of ≤60 mL/min/1.73 m2. RESULTS During follow-up, 270 deaths occurred. LTPA and all its components were associated with all-cause mortality, even after adjustment for the potential confounders sex, diabetic nephropathy, duration of diabetes, age at onset of diabetes, systolic blood pressure, triglycerides, BMI, and HbA1c. Only exercise intensity was associated with cardiovascular mortality after adjustment for the confounders. Of the patients with CKD, 127 died during follow-up. The total amount of LTPA and exercise frequency were independently associated with lower risk of all-cause mortality when adjusted for covariates. CONCLUSIONS Exercise is associated with a lower risk of premature all-cause and cardiovascular mortality in patients with type 1 diabetes. This study also demonstrates that physical activity is associated with a lower risk of mortality in patients with type 1 diabetes and CKD.

    更新日期:2017-10-26
  • Hyperbaric Oxygen Therapy in the Treatment of Ischemic Lower Extremity Ulcers in Patients With Diabetes: Results of the DAMO2CLES Multicenter Randomized Clinical Trial
    Diabetes Care (IF 11.857) Pub Date : 2017-10-25
    Katrien T.B. Santema; Robert M. Stoekenbroek; Mark J.W. Koelemay; Jim A. Reekers; Laura M.C. van Dortmont; Arno Oomen; Luuk Smeets; Jan J. Wever; Dink A. Legemate; Dirk T. Ubbink

    OBJECTIVE Conflicting evidence exists on the effects of hyperbaric oxygen therapy (HBOT) in the treatment of chronic ischemic leg ulcers. The aim of this trial was to investigate whether additional HBOT would benefit patients with diabetes and ischemic leg ulcers. RESEARCH DESIGN AND METHODS Patients with diabetes with an ischemic wound (n = 120) were randomized to standard care (SC) without or with HBOT (SC+HBOT). Primary outcomes were limb salvage and wound healing after 12 months, as well as time to wound healing. Other end points were amputation-free survival (AFS) and mortality. RESULTS Both groups contained 60 patients. Limb salvage was achieved in 47 patients in the SC group vs. 53 patients in the SC+HBOT group (risk difference [RD] 10% [95% CI −4 to 23]). After 12 months, 28 index wounds were healed in the SC group vs. 30 in the SC+HBOT group (RD 3% [95% CI −14 to 21]). AFS was achieved in 41 patients in the SC group and 49 patients in the SC+HBOT group (RD 13% [95% CI −2 to 28]). In the SC+HBOT group, 21 patients (35%) were unable to complete the HBOT protocol as planned. Those who did had significantly less major amputations and higher AFS (RD for AFS 26% [95% CI 10–38]). CONCLUSIONS Additional HBOT did not significantly improve complete wound healing and limb salvage in patients with diabetes and lower limb ischemia.

    更新日期:2017-10-26
  • Improving the Clinical Value and Utility of CGM Systems: Issues and Recommendations
    Diabetes Care (IF 11.857) Pub Date : 2017-10-24
    John R. Petrie; Anne L. Peters; Richard M. Bergenstal; Reinhard W. Holl; G. Alexander Fleming; Lutz Heinemann

    The first systems for continuous glucose monitoring (CGM) became available over 15 years ago. Many then believed CGM would revolutionize the use of intensive insulin therapy in diabetes; however, progress toward that vision has been gradual. Although increasing, the proportion of individuals using CGM rather than conventional systems for self-monitoring of blood glucose on a daily basis is still low in most parts of the world. Barriers to uptake include cost, measurement reliability (particularly with earlier-generation systems), human factors issues, lack of a standardized format for displaying results, and uncertainty on how best to use CGM data to make therapeutic decisions. This Scientific Statement makes recommendations for systemic improvements in clinical use and regulatory (pre- and postmarketing) handling of CGM devices. The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and health outcomes for more people with diabetes.

    更新日期:2017-10-26
  • In This Issue of Diabetes Care
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    American Diabetes Association

    By Max Bingham, PhD Skipping breakfast likely leads to alterations in the way circadian clock genes are expressed with the result being altered glucose regulation, particularly after lunch. According to Jakubowicz et al. ( p. 1573 ), this occurs in both healthy individuals and those with type 2 diabetes, but importantly it points to breakfast consumption as being a potential strategy for glycemic control in type 2 diabetes. Using a crossover study design, the authors randomly assigned healthy individuals ( n = 18) and individuals with established type 2 diabetes ( n = 18) to a test day with breakfast and lunch and a day with only lunch. Clock-related gene expression was then assessed in blood samples before and after the meals, along with plasma glucose, insulin, glucagon-like peptide 1 (GLP-1), and dipeptidyl peptidase IV activity. Skipping breakfast did alter gene expression, but in both healthy individuals and individuals with type 2 diabetes. Skipping breakfast also resulted in a notable drop in insulin response after lunch in individuals with type 2 diabetes while the glucose spike following lunch was much greater. In both groups, GLP-1 response was ∼35% lower when breakfast was skipped. While the authors cover a number of genes involved in circadian rhythms, they highlight specifically that Ampk expression levels fell when breakfast was skipped but were upregulated when it was consumed. The significance? AMPK activation is known to stimulate glucose uptake, so the upregulation probably indicates improved glycemic control. According to author Oren Froy: “As breakfast skipping adversely affects clock and clock-controlled gene expression and is correlated with increased postprandial glycemic response, consumption of breakfast should be an important strategy when targeting glycemic control in type 2 diabetes. In addition, as the circadian clock controls …

    更新日期:2017-10-24
  • Type 2 Diabetes in the Real World: The Elusive Nature of Glycemic Control
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    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:2017-10-24
  • The Promise and Practice of Genetics on Diabetes Care: The Fog Rises to Reveal a Field of Genetic Complexity in HNF1B
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    Stephen S. Rich

    Diabetes is a common disease characterized by the disruption of glucose homeostasis that results when insulin, the hormone that converts glucose from the blood into energy used by the body’s cellular machinery, is absent (through autoimmune destruction of the pancreatic β-cells in type 1 diabetes) or inefficient (increased insulin resistance or reduced insulin sensitivity in type 2 diabetes). There are multiple pathways to developing diabetes, yet practically all involve an underlying genetic etiology with an environmental trigger. The extent of knowledge of genetic factors and environmental factors differs across the forms of diabetes. In the case of type 1 diabetes, the concordance in monozygotic twins (genetically identical) is ∼50%, with familial aggregation and modeling suggesting a major impact of genetics on risk (1). The genetic contribution to type 1 diabetes is well described, with HLA genes accounting for one-half of the genetic risk (2) and ∼50 other sites in the genome contributing the majority of the remaining genetic risk (3). The familial (heritable) contribution to type 2 diabetes has also been estimated through twin studies, with monozygotic twin concordance rising from ∼50% in middle age to nearly 80% later in life (4). Complexity in assessment of the contribution of genetic factors to type 2 diabetes arises from the impact of other familial and behavioral factors that are associated with risk, including obesity, reduced physical activity, and dietary habits. Although the overall risk of type 2 diabetes appears “more heritable” than type 1 diabetes, the estimated effects of ∼100 sites across the genome account for ∼10% of the risk (5). Similar investigations have shown other types of diabetes to be heritable, including neonatal diabetes (6), maturity-onset diabetes of the young (MODY) (7), gestational diabetes mellitus (8), and latent autoimmune diabetes in adults (LADA) (9), and numerous studies have shown diabetes complications …

    更新日期:2017-10-24
  • Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B (HNF1B) Molecular Defects
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    Danièle Dubois-Laforgue; Erika Cornu; Cécile Saint-Martin; Joël Coste; Christine Bellanné-Chantelot; José Timsit

    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 years 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 stages 3–4 (CKD3–4) 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 less often had 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:2017-10-24
  • Effect of a Behavioral Intervention Strategy for Adoption and Maintenance of a Physically Active Lifestyle: The Italian Diabetes and Exercise Study 2 (IDES_2)
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    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

    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 (IDES_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 an 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:2017-10-24
  • What End Users and Stakeholders Want From Automated Insulin Delivery Systems
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    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:2017-10-24
  • Cut Points for Identifying Clinically Significant Diabetes Distress in Adolescents With Type 1 Diabetes Using the PAID-T: Results From Diabetes MILES Youth–Australia
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    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–teen version (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. ANOVA was 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:2017-10-24
  • Understanding the Gap Between Efficacy in Randomized Controlled Trials and Effectiveness in Real-World Use of GLP-1 RA and DPP-4 Therapies in Patients With Type 2 Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    Ginger S. Carls; Edward Tuttle; Ruo-Ding Tan; Johnny Huynh; John Yee; Steven V. Edelman; William H. Polonsky

    OBJECTIVE The 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-1 RA) or dipeptidyl peptidase 4 (DPP-4) inhibitor 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-1 RA (n = 221) or a DPP-4 (n = 652) experienced smaller reductions in HbA1c (GLP-1 RA: −0.52% [−6 mmol/mol], DPP-4: −0.51% [−6 mmol/mol])than reported in RCTs (−1.30% [−14 mmol/mol] from seven GLP-1 RA RCTs, n = 2,600; −0.68% [−8 mmol/mol] from four DPP-4 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-1 RA [−12 mmol/mol], −0.69% DPP-4 [−8 mmol/mol]) were within the RCTs’ reported range (GLP-1 RA: −0.84% to −1.60% [−9 to −18 mmol/mol], DPP-4: −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] GLP-1 RA; 0.18% [3 mmol/mol] DPP-4). 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:2017-10-24
  • Acute Kidney Injury in Patients on SGLT2 Inhibitors: A Propensity-Matched Analysis
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    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 (Kidney Disease: Improving Global Outcomes) 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:2017-10-24
  • Incidence, Demographics, and Clinical Characteristics of Diabetes of the Exocrine Pancreas (Type 3c): A Retrospective Cohort Study
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    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:2017-10-24
  • Dysglycemia and Index60 as Prediagnostic End Points for Type 1 Diabetes Prevention Trials
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    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 a T1D Diagnostic Index60 (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- to 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- to 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:2017-10-24
  • Antihyperglycemic Medications: A Claims-Based Estimate of First-line Therapy Use Prior to Initialization of Second-line Medications
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    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 prior to 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:2017-10-24
  • Pharmacologic Differences of Sulfonylureas and the Risk of Adverse Cardiovascular and Hypoglycemic Events
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    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:2017-10-24
  • 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 : 2017-11-01
    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 (ARIC-NCS) (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:2017-10-24
  • Elevated Postoperative Endogenous GLP-1 Levels Mediate Effects of Roux-en-Y Gastric Bypass on Neural Responsivity to Food Cues
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    Jennifer S. ten Kulve; Dick J. Veltman; Victor E.A. Gerdes; Liselotte van Bloemendaal; Frederik Barkhof; Carolyn F. Deacon; Jens J. Holst; Madeleine L. Drent; Michaela Diamant; Richard G. IJzerman

    OBJECTIVE It has been suggested that weight reduction and improvements in satiety after Roux-en-Y gastric bypass (RYGB) are partly mediated via postoperative neuroendocrine changes. Glucagon-like peptide-1 (GLP-1) is a gut hormone secreted after food ingestion and is associated with appetite and weight reduction, mediated via effects on the central nervous system (CNS). Secretion of GLP-1 is greatly enhanced after RYGB. We hypothesized that postoperative elevated GLP-1 levels contribute to the improved satiety regulation after RYGB via effects on the CNS. RESEARCH DESIGN AND METHODS Effects of the GLP-1 receptor antagonist exendin 9-39 (Ex9-39) and placebo were assessed in 10 women before and after RYGB. We used functional MRI to investigate CNS activation in response to visual food cues (pictures) and gustatory food cues (consumption of chocolate milk), comparing results with Ex9-39 versus placebo before and after RYGB. RESULTS After RYGB, CNS activation was reduced in the rolandic operculum and caudate nucleus in response to viewing food pictures ( P = 0.03) and in the insula in response to consumption of palatable food ( P = 0.003). GLP-1 levels were significantly elevated postoperatively ( P < 0.001). After RYGB, GLP-1 receptor blockade resulted in a larger increase in activation in the caudate nucleus in response to food pictures ( P = 0.02) and in the insula in response to palatable food consumption ( P = 0.002). CONCLUSIONS We conclude that the effects of RYGB on CNS activation in response to visual and gustatory food cues may be mediated by central effects of GLP-1. Our findings provide further insights into the mechanisms underlying the weight-lowering effects of RYGB.

    更新日期:2017-10-24
  • Pioglitazone Improves Left Ventricular Diastolic Function in Subjects With Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    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:2017-10-24
  • 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 : 2017-11-01
    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:2017-10-24
  • 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 : 2017-11-01
    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 (FDS2). 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:2017-10-24
  • 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 : 2017-11-01
    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/day) 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:2017-10-24
  • Longitudinal Change in Fasting Blood Glucose and Myocardial Infarction Risk in a Population Without Diabetes
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    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 from 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 from 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:2017-10-24
  • 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 : 2017-11-01
    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 crossover 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:2017-10-24
  • Does Cardiorespiratory Fitness Attenuate the Adverse Effects of Severe/Morbid Obesity on Cardiometabolic Risk and Insulin Resistance in Children? A Pooled Analysis
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    Christine Delisle Nyström; Pontus Henriksson; Vicente Martínez-Vizcaíno; María Medrano; Cristina Cadenas-Sanchez; Natalia María Arias-Palencia; Marie Löf; Jonatan R. Ruiz; Idoia Labayen; Mairena Sánchez-López; Francisco B. Ortega

    OBJECTIVE To investigate 1) differences in cardiometabolic risk and HOMA of insulin resistance (HOMA-IR) across BMI categories (underweight to morbid obesity), 2) whether fit children have lower cardiometabolic risk/HOMA-IR than unfit children in each BMI category, and 3) differences in cardiometabolic risk/HOMA-IR in normal-weight unfit children and obese fit children. RESEARCH DESIGN AND METHODS A pooled study including cross-sectional data from three projects (n = 1,247 children aged 8–11 years). Cardiometabolic risk was assessed using the sum of the sex- and age-specific z scores for triglycerides, HDL cholesterol, glucose, and the average of systolic and diastolic blood pressure and HOMA-IR. RESULTS A significant linear association was observed between the risk score and BMI categories (P trend ≤0.001), with every incremental rise in BMI category being associated with a 0.5 SD higher risk score (standardized β = 0.474, P < 0.001). A trend was found showing that as BMI categories rose, cardiorespiratory fitness (CRF) attenuated the risk score, with the biggest differences observed in the most obese children (−0.8 SD); however, this attenuation was significant only in mild obesity (−0.2 SD, P = 0.048). Normal-weight unfit children had a significantly lower risk score than obese fit children (P < 0.001); however, a significant reduction in the risk score was found in obese fit compared with unfit children (−0.4 SD, P = 0.027). Similar results were obtained for HOMA-IR. CONCLUSIONS As BMI categories rose so did cardiometabolic risk and HOMA-IR, which highlights the need for obesity prevention/treatment programs in childhood. Furthermore, CRF may play an important role in lowering the risk of cardiometabolic diseases in obese children.

    更新日期:2017-10-24
  • Association Between Adherence to Pharmacotherapy and Outcomes in Type 2 Diabetes: A Meta-analysis
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    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:2017-10-24
  • Prognostic Impact of Diabetes on Long-term Survival Outcomes in Patients With Heart Failure: A Meta-analysis
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    Marco Dauriz; Alessandro Mantovani; Stefano Bonapace; Giuseppe Verlato; Giacomo Zoppini; Enzo Bonora; Giovanni Targher

    OBJECTIVE Several studies have explored the impact of diabetes on mortality in patients with heart failure (HF). However, the extent to which diabetes may confer risk of mortality and hospitalization in this patient population remains imperfectly known. Here we examine the independent prognostic impact of diabetes on the long-term risk of mortality and hospitalization in patients with HF. RESEARCH DESIGN AND METHODS PubMed, Scopus, and Web of Science from January 1990 to October 2016 were the data sources used. We included large (n ≥1,000) observational registries and randomized controlled trials with a follow-up duration of at least 1 year. Eligible studies were selected according to predefined keywords and clinical outcomes. Data from selected studies were extracted, and meta-analysis was performed using random-effects modeling. RESULTS A total of 31 registries and 12 clinical trials with 381,725 patients with acute and chronic HF and 102,036 all-cause deaths over a median follow-up of 3 years were included in the final analysis. Diabetes was associated with a higher risk of all-cause death (random-effects hazard ratio [HR] 1.28 [95% CI 1.21, 1.35]), cardiovascular death (1.34 [1.20, 1.49]), hospitalization (1.35 [1.20, 1.50]), and the combined end point of all-cause death or hospitalization (1.41 [1.29, 1.53]). The impact of diabetes on mortality and hospitalization was greater in patients with chronic HF than in those with acute HF. Limitations included high heterogeneity and varying degrees of confounder adjustment across individual studies. CONCLUSIONS This updated meta-analysis shows that the presence of diabetes per se adversely affects long-term survival and risk of hospitalization in patients with acute and chronic HF.

    更新日期:2017-10-24
  • Erratum. Cardiovascular Disease and Type 2 Diabetes: Has the Dawn of a New Era Arrived? Diabetes Care 2017;40:813–820
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    Muhammad Abdul-Ghani; Ralph A. DeFronzo; Stefano Del Prato; Robert Chilton; Rajvir Singh; Robert E.J. Ryder

    In the article listed above, the sentence on page 814 that reads “There also were more serious hypoglycemic events …

    更新日期:2017-10-24
  • Erratum. Application of Zone Model Predictive Control Artificial Pancreas During Extended Use of Infusion Set and Sensor: A Randomized Crossover-Controlled Home-Use Trial. Diabetes Care 2017;40:1096–1102
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    Gregory P. Forlenza; Sunil Deshpande; Trang T. Ly; Daniel P. Howsmon; Faye Cameron; Nihat Baysal; Eric Mauritzen; Tatiana Marcal; Lindsey Towers; B. Wayne Bequette; Lauren M. Huyett; Jordan E. Pinsker; Ravi Gondhalekar; Francis J. Doyle; David M. Maahs; Bruce A. Buckingham; Eyal Dassau

    In the above-mentioned article, the supplementary data had the incorrect figure listed for …

    更新日期:2017-10-24
  • Issues and Events
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    American Diabetes Association

    The American Diabetes Association offers a variety of continuing education opportunities and materials for health care professionals. Educational offerings include live and free online programs. For more information, including a complete list of American Diabetes Association programs, please visit professional.diabetes.org/ce. The 78th annual American Diabetes Association Scientific Sessions will be held in Orlando, Florida, on 22–26 June 2018, at the Orange County Convention Center. The largest of its kind, this meeting brings together scientists and health care …

    更新日期:2017-10-24
  • Comment on Lovshin et al. Dipeptidyl Peptidase 4 Inhibition Stimulates Distal Tubular Natriuresis and Increases in Circulating SDF-1α1-67 in Patients With Type 2 Diabetes. Diabetes Care 2017;40:1073–1081
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    Michaël J.B. van Baar; Daniël H. van Raalte; Marcel H.A. Muskiet

    We read with interest the study by Lovshin et al. (1) investigating the natriuretic effect of the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin in patients with type 2 diabetes (T2D). The authors report that 1 month of sitagliptin therapy increases creatinine-based fractional sodium excretion (FENa) compared with placebo, which is in line with our previous observation (2). As lithium clearance and (intra)renal hemodynamics were not affected, the authors suggest that sitagliptin inhibits tubular sodium reabsorption at a level that is likely downstream of the macula densa. In parallel with enhanced FENa, DPP-4 inhibition increased intact stromal cell–derived factor (SDF)-1α1–67 levels, suggesting a relevant natriuretic role for this DPP-4 substrate. We agree with the authors that their mechanistic findings are of potential clinical relevance, particularly when hypothesizing about the added natriuretic effect of combined pharmacological DPP-4/sodium–glucose cotransporter …

    更新日期:2017-10-24
  • Response to Comment on Lovshin et al. Dipeptidyl Peptidase 4 Inhibition Stimulates Distal Tubular Natriuresis and Increases in Circulating SDF-1α1-67 in Patients With Type 2 Diabetes. Diabetes Care 2017;40:1073-1081
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    Julie A. Lovshin; Leif E. Lovblom; David Z.I. Cherney

    We thank van Baar et al. (1) for their interest in our study (2). We agree that the chronic natriuretic effect(s) of the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin occurred in the early postprandial state (3 h after a standardized liquid meal during a euglycemic clamp). We cannot, however, rule out that DPP-4 inhibitor–mediated effect(s) on natriuresis persisted for several hours after this sampling period. Recognizing feasibility concerns around having research participants in a highly controlled research setting for prolonged periods, we limited our fractional sodium excretion (FENA) and renal hemodynamic function measurements to 3 h. This was in addition to the 4–5 h that patients had already been in the lab for baseline testing. We agree that …

    更新日期:2017-10-24
  • Comment on Ely et al. A National Effort to Prevent Type 2 Diabetes: Participant-Level Evaluation of CDC’s National Diabetes Prevention Program. Diabetes Care 2017;40:1331–1341
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    Natalie D. Ritchie; Peter Kaufmann; Katherine A. Sauder

    Ely et al. (1) from the Centers for Disease Control and Prevention (CDC) provide a first report of National Diabetes Prevention Program (National DPP) effectiveness since its 2012 launch. It is impressive that 4.2% mean weight loss was achieved in a large-scale translation of the original DPP (1), which obtained 4.9% weight loss with the rigor of a randomized controlled trial (2). However, only approximately 0.04% of the 86 million adults in the U.S. with prediabetes were reached in 4 years of implementation (1). Moreover, the authors did not address two critical implications of the findings: 1 ) future reach of the National DPP is projected to decrease, and 2 ) the program may contribute to, rather than ameliorate, health disparities as currently implemented. First, the authors briefly noted recognition is …

    更新日期:2017-10-24
  • Response to Comment on Ely et al. A National Effort to Prevent Type 2 Diabetes: Participant-Level Evaluation of CDC’s National Diabetes Prevention Program. Diabetes Care 2017;40:1331–1341
    Diabetes Care (IF 11.857) Pub Date : 2017-11-01
    Elizabeth K. Ely; Stephanie M. Gruss; Elizabeth T. Luman; Ann L. Albright

    In response to Ritchie et al. (1) regarding the first report from the Centers for Disease Control and Prevention (CDC) of findings from the National Diabetes Prevention Program (National DPP) (2), we respectfully submit the following. Our article (2) is an initial, preliminary report of data from the first few years of program implementation and data collection only. It describes the experience of 14,747 adults enrolled in year-long type 2 diabetes prevention programs from February 2012 through January 2016. As of July 2017, the National DPP had …

    更新日期:2017-10-24
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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