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  • Fasting C-peptide is a significant indicator of nonalcoholic fatty liver disease in obese children
    Diabetes Res. Clin. Pract. (IF 3.239) Pub Date : 2020-01-17
    Xiucui Han; Pengfei Xu; Jianming Zhou; Yongxia Liu; Hui Xu

    Aims Whether fasting C-peptide can be a potential indicator for nonalcoholic fatty liver disease (NAFLD) in obese children is unknown. This study aimed to assess whether fasting C-peptide represented a risk factor for NAFLD. Methods A total of 520 obese children (376 male, 144 female) aged 3.4-17.1 years were divided into two groups, obese with NAFLD and non-NAFLD, according to hepatic ultrasound results. Fasting plasma glucose, fasting C-peptide, hemoglobin A1c, renal function, liver function, blood lipid, fasting insulin and blood routine indices were measured. Insulin resistance by homoeostasis model (HOMA-IR) was calculated. Results Compared with the non-NAFLD group, the obese children with NAFLD had higher fasting C-peptide, fasting insulin and HOMA-IR (P < 0.001). Stepwise multiple logistic regression models showed that fasting C-peptide (odds ratio: OR = 2.367) was independent indicator of the presence of NAFLD in obese children as well as white blood cell (OR = 1.113), albumin (OR = 1.124), alanine aminotransferase(OR=1.030), triglycerides(OR=1.335), and waist circumference (OR=1.047). Furthermore, after adjustment for confounding variables, the prevalence of NAFLD in obese children was significantly higher according to increased serum fasting C-peptide levels. The adjusted OR for NAFLD according to fasting C-peptide tertiles were 1.00(as references), 1.896(1.045-3.436), and 4.169(1.822-9.537). Conclusion Our data suggested that obese children with high level of fasting C-peptide had an increased risk for developing NAFLD.

  • Toward a better understanding of the effects of endocrine disrupting compounds on health: Human-relevant case studies from sheep models
    Mol. Cell. Endocrinol. (IF 3.693) Pub Date : 2020-01-16
    Catherine Viguié; Elodie Chaillou; Véronique Gayrard; Nicole Picard-Hagen; Paul A. Fowler

    There are many challenges to overcome in order to properly understand both the exposure to, and effects of, endocrine disruptors (EDs). This is particularly true with respect to fetal life where ED exposures are a major issue requiring toxicokinetic studies of materno-fetal exchange and identification of pathophysiological consequences. The sheep, a monotocous large size species is very suitable for in utero fetal catheterization allowing a modelling approach predictive of human fetal exposure. Predicting adverse effects of EDs on human health is frequently impeded by the wide interspecies differences in the regulation of endocrine functions and their effect on biological processes. Because of its similarity to humans as regards gestational and thyroid physiologies and brain ontogeny, the sheep constitutes a highly appropriate model to move one step further on thyroid disruptor hazard assessment. As a grazing animal, sheep has also been proven to be useful in the evaluation of the consequences of chronic environmental exposure to “real-life” complex mixtures at different stages of the reproductive life cycle.

  • A noninferiority within-person study comparing the accuracy of transperineal to transrectal MRI–US fusion biopsy for prostate-cancer detection
    Prostate Cancer Prostatic. Dis. (IF 4.600) Pub Date : 2020-01-17
    Yaara Ber; Niv Segal; Shlomit Tamir; Ofer Benjaminov; Maxim Yakimov; Sivan Sela; Daniel Halstauch; Jack Baniel; Daniel Kedar; David Margel
  • Retinopathy in a Diet-Induced Type 2 Diabetic Rat Model, and Role of Epigenetic Modifications
    Diabetes (IF 7.199) Pub Date : 2020-01-16
    Renu A. Kowluru

    Type 2 diabetes accounts for 90% of diabetic population, and these patients are generally obese and hyperlipidemic. In addition to hyperglycemia, hyperlipidemia is also closely related with diabetic retinopathy. Aim was to investigate retinopathy in a model closely mimicking the normal progression and metabolic features of type 2 diabetic population, and elucidate the molecular mechanism. Retinopathy was evaluated in rats fed 45% kcal as fat diet for eight weeks before administering streptozotocin, 30mg/kg BW (T2D), and was compared with age- and duration-matched type 1 diabetic rats (T1D, 60mg/kg streptozotocin). The role of epigenetic modifications in mitochondrial damage was evaluated in retinal microvasculature. T2D rats were obese and severely hyperlipidemic, with impaired glucose and insulin tolerance compared to age-matched T1D rats. While at four months of diabetes, T1D rats had no detectable retinopathy, T2D rats had significant retinopathy, their mitochondrial copy numbers were lower, and mtDNA and Rac1 promoter DNA methylation were exacerbated. At six months, retinopathy was comparable in T2D and T1D rats, suggesting that obesity exaggerates hyperglycemia-induced epigenetic modifications, accelerating mitochondrial damage and diabetic retinopathy. Thus, maintenance of good life style and body mass index could be beneficial in regulating epigenetic modifications and preventing/retarding retinopathy in diabetic patients.

  • Five Stages of Evolving Beta-Cell Dysfunction During Progression to Diabetes
    Diabetes (IF 7.199) Pub Date : 2004-12-01
    Gordon C. Weir; Susan Bonner-Weir

    Progression to diabetes can be viewed as having definable stages characterized by changes in various metabolic parameters and β-cell function. At the very beginning, fasting plasma glucose levels increase from perfectly normal values of ∼4.5 mmol/l (80 mg/dl) to higher values that might be as low as 5.0 mmol/l (89 mg/dl). This change in glycemia would not be recognized as being clinically abnormal because it would fail to reach the official category of impaired fasting glucose (IFG; glucose level ≥5.6 mmol/l or 100 mg/dl) or impaired glucose tolerance (IGT; 2-h postglucose level of ≥7.8 mmol/l or 140 mg/dl) (1). Those destined to develop diabetes then progress to the IFG or IGT range, where they may remain for years before developing frank diabetes. Although this progression is mostly discussed in the context of type 2 diabetes, very similar changes occur as type 1 diabetes unfolds and as pancreas or islet transplants fail.

  • The Multiple Actions of GLP-1 on the Process of Glucose-Stimulated Insulin Secretion
    Diabetes (IF 7.199) Pub Date : 2002-12-01
    Patrick E. MacDonald; Wasim El-kholy; Michael J. Riedel; Anne Marie F. Salapatek; Peter E. Light; Michael B. Wheeler

    Glucagon-like peptide 1 (GLP-1) is a potent incretin hormone produced in the L-cells of the distal ileum and colon. In the L-cells, GLP-1 is generated by tissue-specific posttranslational processing of the proglucagon gene (1). Nutrients, including glucose, fatty acids, and dietary fiber, are all known to upregulate the transcription of the gene encoding GLP-1, and they can stimulate the release of this hormone (2). Although the majority of L-cells are located in the distal ileum and colon, the levels of GLP-1 rise rapidly upon food ingestion. It is now well accepted that nutrients, principally sugars and fats, liberate GLP-1 and GLP-1-releasing factors, including glucose-dependent insulinotropic peptide (GIP), gastrin-releasing peptide, and selective neural regulators that also stimulate GLP-1 secretion (rev. in 1–3). Upon its release, GLP-1 affects multiple target tissues throughout the body, actions thought to be mediated by a single G-protein-coupled receptor isoform. GLP-1 receptor transcripts and/or protein have been identified in several tissues, including pancreatic islets, lung, gastrointestinal (GI) tract, and the central nervous system (CNS) (2,3). More questionable is the expression of functional GLP-1 receptors in liver and skeletal muscle tissues, where gene expression has been detected (4). GLP-1’s ability to augment insulin release in a glucose-dependent manner is its most well-characterized physiological effect and one of its most promising characteristics from a clinical perspective.

  • Association of BMI, Fitness, and Mortality in Patients With Diabetes: Evaluating the Obesity Paradox in the Henry Ford Exercise Testing Project (FIT Project) Cohort
    Diabetes Care (IF 15.270) Pub Date : 2020-01-16
    Seamus P. Whelton; Paul A. McAuley; Zeina Dardari; Olusola A. Orimoloye; Clinton A. Brawner; Jonathan K. Ehrman; Steven J. Keteyian; Mouaz Al-Mallah; Michael J. Blaha

    OBJECTIVE To determine the effect of fitness on the association between BMI and mortality among patients with diabetes. RESEARCH DESIGN AND METHODS We identified 8,528 patients with diabetes (self-report, medication use, or electronic medical record diagnosis) from the Henry Ford ExercIse Testing Project (FIT Project). Patients with a BMI <18.5 kg/m2 or cancer were excluded. Fitness was measured as the METs achieved during a physician-referred treadmill stress test and categorized as low (<6), moderate (6–9.9), and high (≥10). Adjusted hazard ratios for mortality were calculated using standard BMI (kilograms per meter squared) cutoffs of normal (18.5–24.9), overweight (25–29.9), and obese (≥30). Adjusted splines centered at 22.5 kg/m2 were used to examine BMI as a continuous variable. RESULTS Patients had a mean age of 58 ± 11 years (49% women) with 1,319 deaths over a mean follow-up of 10.0 ± 4.1 years. Overall, obese patients had a 30% lower mortality hazard ( P < 0.001) compared with normal-weight patients. In adjusted spline modeling, higher BMI as a continuous variable was predominantly associated with a lower mortality risk in the lowest fitness group and among patients with moderate fitness and BMI ≥30 kg/m2. Compared with the lowest fitness group, patients with higher fitness had an ∼50% (6–9.9 METs) and 70% (≥10 METs) lower mortality hazard regardless of BMI ( P < 0.001). CONCLUSIONS Among patients with diabetes, the obesity paradox was less pronounced for patients with the highest fitness level, and these patients also had the lowest risk of mortality.

  • No Acute Effects of Exogenous Glucose-Dependent Insulinotropic Polypeptide on Energy Intake, Appetite, or Energy Expenditure When Added to Treatment With a Long-Acting Glucagon-Like Peptide 1 Receptor Agonist in Men With Type 2 Diabetes
    Diabetes Care (IF 15.270) Pub Date : 2020-01-16
    Natasha C. Bergmann; Lærke S. Gasbjerg; Sebastian M. Heimbürger; Liva S.L. Krogh; Flemming Dela; Bolette Hartmann; Jens J. Holst; Lene Jessen; Mikkel B. Christensen; Tina Vilsbøll; Asger Lund; Filip K. Knop

    OBJECTIVE Dual incretin receptor agonists in clinical development have shown reductions in body weight and hemoglobin A1c (HbA1c) in patients with type 2 diabetes, but the impact of glucose-dependent insulinotropic polypeptide (GIP) receptor activation remains unclear. Here, we evaluated the effects of high-dose exogenous GIP on energy intake, energy expenditure, plasma glucose, and glucose-regulating hormones in patients with type 2 diabetes treated with a long-acting glucagon-like peptide 1 receptor (GLP-1R) agonist. RESEARCH DESIGN AND METHODS In a randomized, double-blind design, men with type 2 diabetes ( n = 22, mean ± SEM HbA1c 6.8 ± 0.1% [51 ± 1.5 mmol/mol]) treated with metformin and long-acting GLP-1R agonists were subjected to two 5-h continuous infusions (separated by a washout period of ≥3 days): one with GIP (6 pmol/kg/min) and another with saline (placebo). After 60 min of infusion, a liquid mixed-meal test was performed and after 270 min of infusion, an ad libitum meal was served for evaluation of energy intake (primary end point). RESULTS Energy intake was similar during GIP and placebo infusion (648 ± 74 kcal vs. 594 ± 55 kcal, respectively; P = 0.480), as were appetite measures and energy expenditure. Plasma glucagon and glucose were higher during GIP infusion compared with placebo infusion ( P = 0.026 and P = 0.017) as assessed by area under the curve. CONCLUSIONS In patients with type 2 diabetes, GIP infusion on top of treatment with metformin and a long-acting GLP-1R agonist did not affect energy intake, appetite, or energy expenditure but increased plasma glucose compared with placebo. These results indicate no acute beneficial effects of combining GIP and GLP-1.

  • Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report
    Diabetes Care (IF 15.270) Pub Date : 2019-05-01
    Alison B. Evert; Michelle Dennison; Christopher D. Gardner; W. Timothy Garvey; Ka Hei Karen Lau; Janice MacLeod; Joanna Mitri; Raquel F. Pereira; Kelly Rawlings; Shamera Robinson; Laura Saslow; Sacha Uelmen; Patricia B. Urbanski; William S. Yancy

    This Consensus Report is intended to provide clinical professionals with evidence-based guidance about individualizing nutrition therapy for adults with diabetes or prediabetes. Strong evidence supports the efficacy and cost-effectiveness of nutrition therapy as a component of quality diabetes care, including its integration into the medical management of diabetes; therefore, it is important that all members of the health care team know and champion the benefits of nutrition therapy and key nutrition messages. Nutrition counseling that works toward improving or maintaining glycemic targets, achieving weight management goals, and improving cardiovascular risk factors (e.g., blood pressure, lipids, etc.) within individualized treatment goals is recommended for all adults with diabetes and prediabetes. Though it might simplify messaging, a “one-size-fits-all” eating plan is not evident for the prevention or management of diabetes, and it is an unrealistic expectation given the broad spectrum of people affected by diabetes and prediabetes, their cultural backgrounds, personal preferences, co-occurring conditions (often referred to as comorbidities), and socioeconomic settings in which they live. Research provides clarity on many food choices and eating patterns that can help people achieve health goals and quality of life. The American Diabetes Association (ADA) emphasizes that medical nutrition therapy (MNT) is fundamental in the overall diabetes management plan, and the need for MNT should be reassessed frequently by health care providers in collaboration with people with diabetes across the life span, with special attention during times of changing health status and life stages (1–3). This Consensus Report now includes information on prediabetes, and previous ADA nutrition position statements, the last of which was published in 2014 (4), did not. Unless otherwise noted, the research reviewed was limited to those studies conducted in adults diagnosed with prediabetes, type 1 diabetes, and/or type 2 diabetes. Nutrition therapy for children with diabetes or women …

  • Amount and Type of Dietary Fat, Postprandial Glycemia, and Insulin Requirements in Type 1 Diabetes: A Randomized Within-Subject Trial
    Diabetes Care (IF 15.270) Pub Date : 2020-01-01
    Kirstine J. Bell; Chantelle Z. Fio; Stephen Twigg; Sally-Anne Duke; Gregory Fulcher; Kylie Alexander; Margaret McGill; Jencia Wong; Jennie Brand-Miller; Garry M. Steil

    OBJECTIVE The American Diabetes Association recommends individuals with type 1 diabetes (T1D) adjust insulin for dietary fat; however, optimal adjustments are not known. This study aimed to determine 1 ) the relationship between the amount and type of dietary fat and glycemia and 2 ) the optimal insulin adjustments for dietary fat. RESEARCH DESIGN AND METHODS Adults with T1D using insulin pump therapy attended the research clinic on 9–12 occasions. On the first six visits, participants consumed meals containing 45 g carbohydrate with 0 g, 20 g, 40 g, or 60 g fat and either saturated, monounsaturated, or polyunsaturated fat. Insulin was dosed using individual insulin/carbohydrate ratio as a dual-wave 50/50% over 2 h. On subsequent visits, participants repeated the 20–60-g fat meals with the insulin dose estimated using a model predictive bolus, up to twice per meal, until glycemic control was achieved. RESULTS With the same insulin dose, increasing the amount of fat resulted in a significant dose-dependent reduction in incremental area under the curve for glucose (iAUCglucose) in the early postprandial period (0–2 h; P = 0.008) and increase in iAUCglucose in the late postprandial period (2–5 h; P = 0.004). The type of fat made no significant difference to the 5-h iAUCglucose. To achieve glycemic control, on average participants required dual-wave insulin bolus: for 20 g fat, +6% insulin, 74/26% over 73 min; 40 g fat, +6% insulin, 63/37% over 75 min; and 60 g fat, +21% insulin, 49/51% over 105 min. CONCLUSIONS This study provides clinical guidance for mealtime insulin dosing recommendations for dietary fat in T1D.

  • Urinary and Serum Angiogenic Markers in Women With Preexisting Diabetes During Pregnancy and Their Role in Preeclampsia Prediction
    Diabetes Care (IF 15.270) Pub Date : 2020-01-01
    Monica Zen; Suja Padmanabhan; Kewei Zhang; Adrienne Kirby; N. Wah Cheung; Vincent W. Lee; Thushari I. Alahakoon

    OBJECTIVE To determine the correlation between urinary and serum placental growth factor (PlGF) and investigate the predictive value as pregnancy progresses of urinary PlGF compared with serum PlGF, soluble fms-like tyrosine kinase 1 (sFLT-1), and the sFLT-1–to–PlGF ratio for the outcome of preeclampsia in women with preexisting diabetes. RESEARCH DESIGN AND METHODS A multicenter prospective cohort study was conducted of 158 women with preexisting insulin-requiring diabetes (41 with type 1 and 117 with type 2). Urinary PlGF and serum PlGF, sFLT-1, and the sFLT-1–to–PlGF ratio were assessed four times (14, 24, 30, and 36 weeks’ gestation), and the association with the outcome of preeclampsia was investigated. RESULTS A correlation between urinary and serum PlGF was demonstrated from 24 weeks’ gestation onward ( P < 0.001). At all time points, those who developed preeclampsia had lower serum PlGF levels ( P < 0.05), and receiver operating characteristic curves demonstrated that serum PlGF in this cohort performed better than the serum sFLT-1–to–PlGF ratio as a predictive test for preeclampsia. Preconception HbA1c ≥6.5% (48 mmol/mol) was an important discriminative predictor for preeclampsia ( P = 0.01). CONCLUSIONS This study prospectively describes the longitudinal changes in urinary PlGF alongside serum angiogenic markers throughout pregnancy in women with preexisting diabetes. We demonstrate correlation between urinary and serum PlGF and that in women with preexisting diabetes in pregnancy, serum PlGF is a better predictor of preeclampsia than the sFLT-1–to–PlGF ratio.

  • Excessive Weight Gain Before and During Gestational Diabetes Mellitus Management: What Is the Impact?
    Diabetes Care (IF 15.270) Pub Date : 2020-01-01
    Robyn A. Barnes; Tang Wong; Glynis P. Ross; Michelle M. Griffiths; Carmel E. Smart; Clare E. Collins; Lesley MacDonald-Wicks; Jeff R. Flack

    OBJECTIVE Conventional gestational diabetes mellitus (GDM) management focuses on managing blood glucose in order to prevent adverse outcomes. We hypothesized that excessive weight gain at first presentation with GDM (excessive gestational weight gain [EGWG]) and continued EGWG (cEGWG) after commencing GDM management would increase the risk of adverse outcomes, despite treatment to optimize glycemia. RESEARCH DESIGN AND METHODS Data collected prospectively from pregnant women with GDM at a single institution were analyzed. GDM was diagnosed on the basis of Australasian Diabetes in Pregnancy Society 1998 guidelines (1992–2015). EGWG means having exceeded the upper limit of the Institute of Medicine–recommended target ranges for the entire pregnancy, by GDM presentation. The relationship between EGWG and antenatal 75-g oral glucose tolerance test (oGTT) values and adverse outcomes was evaluated. Relationships were examined between cEGWG, insulin requirements, and large-for-gestational-age (LGA) infants. RESULTS Of 3,281 pregnant women, 776 (23.6%) had EGWG. Women with EGWG had higher mean fasting plasma glucose (FPG) on oGTT (5.2 mmol/L [95% CI 5.1–5.3] vs. 5.0 mmol/L [95% CI 4.9–5.0]; P < 0.01), after adjusting for confounders, and more often received insulin therapy (47.0% vs. 33.6%; P < 0.0001), with an adjusted odds ratio (aOR) of 1.4 (95% CI 1.1–1.7; P < 0.01). aORs for each 2-kg increment of cEGWG were a 1.3-fold higher use of insulin therapy (95% CI 1.1–1.5; P < 0.001), an 8-unit increase in final daily insulin dose (95% CI 5.4–11.0; P < 0.0001), and a 1.4-fold increase in the rate of delivery of LGA infants (95% CI 1.2–1.7; P < 0.0001). CONCLUSIONS The absence of EGWG and restricting cEGWG in GDM have a mitigating effect on oGTT-based FPG, the risk of having an LGA infant, and insulin requirements.

  • Absence of Islet Autoantibodies and Modestly Raised Glucose Values at Diabetes Diagnosis Should Lead to Testing for MODY: Lessons From a 5-Year Pediatric Swedish National Cohort Study
    Diabetes Care (IF 15.270) Pub Date : 2020-01-01
    Annelie Carlsson; Maggie Shepherd; Sian Ellard; Michael Weedon; Åke Lernmark; Gun Forsander; Kevin Colclough; Qefsere Brahimi; Camilla Valtonen-Andre; Sten A. Ivarsson; Helena Elding Larsson; Ulf Samuelsson; Eva Örtqvist; Leif Groop; Johnny Ludvigsson; Claude Marcus; Andrew T. Hattersley

    OBJECTIVE Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population. RESEARCH DESIGN AND METHODS Swedish patients ( n = 3,933) aged 1–18 years, diagnosed with diabetes May 2005 to December 2010, were recruited from the national consecutive prospective cohort Better Diabetes Diagnosis. Clinical data, islet autoantibodies (GAD insulinoma antigen-2, zinc transporter 8, and insulin autoantibodies), HLA type, and C-peptide were collected at diagnosis. MODY was identified by sequencing GCK , HNF1A , and HNF4A , through either routine clinical or research testing. RESULTS The minimal prevalence of MODY was 1.2%. Discriminatory factors for MODY at diagnosis included four islet autoantibody negativity (100% vs. 11% not-known MODY; P = 2 × 10−44), HbA1c (7.0% vs. 10.7% [53 vs. 93 mmol/mol]; P = 1 × 10−20), plasma glucose (11.7 vs. 26.7 mmol/L; P = 3 × 10−19), parental diabetes (63% vs. 12%; P = 1 × 10−15), and diabetic ketoacidosis (0% vs. 15%; P = 0.001). Testing 303 autoantibody-negative patients identified 46 patients with MODY (detection rate 15%). Limiting testing to the 73 islet autoantibody-negative patients with HbA1c <7.5% (58 mmol/mol) at diagnosis identified 36 out of 46 (78%) patients with MODY (detection rate 49%). On follow-up, the 46 patients with MODY had excellent glycemic control, with an HbA1c of 6.4% (47 mmol/mol), with 42 out of 46 (91%) patients not on insulin treatment. CONCLUSIONS At diagnosis of pediatric diabetes, absence of all islet autoantibodies and modest hyperglycemia (HbA1c <7.5% [58 mmol/mol]) should result in testing for GCK, HNF1A, and HNF4A MODY. Testing all 12% patients negative for four islet autoantibodies is an effective strategy for not missing MODY but will result in a lower detection rate. Identifying MODY results in excellent long-term glycemic control without insulin.

  • Elevation of the renal threshold for glucose is associated with insulin resistance and higher glycated hemoglobin levels
    J. Diabetes Investig. (IF 3.902) Pub Date : 2020-01-15
    Kunio Hieshima; Seigo Sugiyama; Akira Yoshida; Noboru Kurinami; Tomoko Suzuki; Hiroko Ijima; Fumio Miyamoto; Keizo Kajiwara; Katsunori Jinnouchi; Tomio Jinnouchi; Hideaki Jinnouchi
  • 更新日期:2020-01-16
  • Higher versus standard starting dose of insulin glargine 100 U/mL in overweight or obese Chinese patients with type 2 diabetes: results of a multicentre, open‐label, randomised controlled trial (BEYOND VII)
    Diabetes Obes. Metab. (IF 6.133) Pub Date : 2020-01-15
    Linong Ji; Hailong Wan; Binhong Wen; Xueying Wang; Junfen Wang; Rongwen Bian; Wuyan Pang; Jian Tian; Yan Wang; Fang Bian; Zhengnan Gao; Alex Condoleon; Wei Feng; Xia Zhang; Nan Cui

    To determine the safety of a higher starting dose of basal insulin in overweight/obese patients with type 2 diabetes (T2D).

  • Durability of glycaemic control in patients with type 2 diabetes after metformin failure: prognostic model derivation and validation using the DISCOVER study
    Diabetes Obes. Metab. (IF 6.133) Pub Date : 2020-01-15
    Suping Ling; Ping Sun; Francesco Zaccardi; Sajan Khosla; Andrew Cooper; Peter Fenici; Kamlesh Khunti

    Evidence on long‐term glucose reductions achieved by second‐line glucose‐lowering therapy is scarce.

  • Metformin: an old drug against old age and associated morbidities
    Diabetes Res. Clin. Pract. (IF 3.239) Pub Date : 2020-01-16
    Teresa Salvatore; Pia Clara Pafundi; Floriana Morgillo; Raimondo Di Liello; Raffaele Galiero; Riccardo Nevola; Raffaele Marfella; Lucio Monaco; Luca Rinaldi; Luigi Elio Adinolfi; Ferdinando Carlo Sasso

    Metformin represents a striking example of a “historical nemesis” of a drug. About 40 years after its marketing in Europe, once demonstrated its efficacy and safety, metformin was registered also in the U.S. A few years later, it has become a mainstay in T2DM treatment, according to all international Scientific Societies guidelines. Today, despite the advent of new innovative drugs, metformin still persists as a first-choice drug in T2DM. This success is largely justified. In fact, over the years, also positive effects on health increased. In particular, evidence has been accumulated on a beneficial impact against many other aging-related morbidities (obesity, metabolic syndrome, cardiovascular disease, cancer, cognitive decline and mortality). This literature review describes preclinical and clinical evidence favoring the “anti-aging” therapeutic potential of metformin outside of T2DM. The rationale to the use of metformin as part of a combined therapy in a variety of clinical settings, allowing for a reduction of the chemotherapy dose in cancer patients, has also been discussed. In particular, the focus was on metformin action on RAS/RAF/MAPK pathway. In the end, the real challenge for metformin could be to fully demonstrate beneficial effects on health even in non-diabetic subjects.

  • Insulin pumps use in Greece: efficacy and safety data from 140 patients with type 1 diabetes mellitus
    Diabetes Res. Clin. Pract. (IF 3.239) Pub Date : 2020-01-16
    Maria Somali; Stavroula A. Paschou; Zadalla Mouslech

    Objective The aim of this study was to investigate the efficacy and safety of continuous subcutaneous insulin infusion (CSII) regarding glycaemic control and quality of life in patients with type 1 diabetes mellitus (T1DM), who were previously treated with a multiple daily injections (MDI). Patients and Methods 140 patients with T1DM [mean age 33.7±22.1 years; 54 males, 76 females, 10 children; duration of diabetes 19.1±8.4 years; total daily insulin usage while on MDI (IU/kg/day) 57.86±15.32; HbA1c at the beginning of CSII treatment 8.67±1.54%] were included in the study. HbA1c, glucose levels, BMI, severe hypoglycemic and diabetic ketoacidosis (DKA) episodes were recorded and compared to the data prior to CSII introduction. The evaluation of the quality of life was assessed with a self-questionnaire adjusted from the SF-12 and diabetes quality of life (DQoL) questionnaires. Results HbA1c was reduced from 8.67±1.54 to 6.85±0.52% (p<0.001). This reduction was independent of age, gender, body mass index (BMI) and diabetes duration. Daily insulin requirements were lower at the end of the follow-up (36.40±12.20 IU/kg/day) compared with the needs during enrolment (57.86±15.32 IU/kg/day) (p<0.001). BMI presented no significant alterations. Ten (10) severe hypoglycemic episodes were recorded but the overall rate was decreased by 71.5% (p<0.001). Only 3 cases of ketoacidosis were recorded. Quality of life parameters were remarkably improved. Conclusions This study provided evidence that CSII treatment was superior to MDI for patients with T1DM in Greece. CSII offered a safe, effective alternative to MDI schemes, while improving glycaemic control, side-effects and quality of life.

  • Meta-analysis of the Effectiveness of the Trier Social Stress Test in Eliciting Physiological Stress Responses in Children and Adolescents
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2020-01-16
    Jessica A. Seddon; Violeta J. Rodriguez; Yannick Provencher; Jacquelyn Raftery-Helmer; Jacqueline Hersh; Patrick R. Labelle; Kristel Thomassin

    The Trier Social Stress Test (TSST) is known to reliably induce physiological stress responses in adult samples. Less is known about its effectiveness to elicit these responses in youth samples. We performed a meta-analysis of stress responses to the TSST in youth participants. Fifty-seven studies were included representing 5,026 youth participants. Results indicated that the TSST was effective at eliciting stress responses for salivary cortisol (sCort; effect size [ES] = 0.47, p = .006), heart rate (HR; ES = 0.89, p < .001), pre-ejection period (PEP; ES = -0.37, p < .001), heart rate variability (HRV; ES = -0.33, p = .028), and systolic blood pressure (ES = 1.17, p < .001), as well as negative affect (ES = 0.57, p = .004) and subjective anxiety (ES = 0.80, p = .004) in youth samples. Cardiac output (ES = 0.15, p = .164), respiratory sinus arrhythmia (ES = -0.10, p = .064), and diastolic blood pressure (ES = 2.36, p = .072) did not reach statistical significance. Overall, effect sizes for the TSST varied based on the physiological marker used. In addition, several physiological markers demonstrated variance in reactivity by youth age (sCort, HR, HRV, and PEP), gender (sCort), type of sample (i.e., clinical versus community sample; sCort and HR), duration of TSST (sCort, HR, HRV, negative affect, and subjective anxiety), number of judges present in TSST (HR and subjective anxiety), gender of judges (sCort), and time of day the marker was assessed (morning versus afternoon/evening; sCort). Overall, the findings provide support for the validity of the TSST as a psychosocial stressor for inducing physiological and psychological stress responses in children and adolescents, but also highlight that some markers may capture the stress response more effectively than others.

  • Use of the triglyceride-glucose index (TyG) in cardiovascular disease patients
    Cardiovasc. Diabetol. (IF 5.948) Pub Date : 2020-01-15
    Javad Alizargar; Chyi-Huey Bai; Nan-Chen Hsieh; Shu-Fang Vivienne Wu

    Da Silva et al. showed that the triglyceride-glucose (TyG) index was positively associated with a higher prevalence of symptomatic coronary artery disease (CAD). TyG has been used in healthy individuals as a marker of insulin resistance. The use of this index as a marker of atherosclerosis in cardiovascular disease (CVD) patients might be influenced by diabetes and the hyperlipidemic state that led to CVD. Certain considerations might be necessary before we conclude that the TyG index can be used as a marker of atherosclerosis in CVD patients. These factors can highlight the role of fasting blood glucose and triglyceride levels that are used in the TyG formula. Comparing the fasting blood glucose and/or triglyceride levels with the TyG index in these patients to show how much value the TyG index can add to clinical practice seems to be necessary. Conclusions of such studies might be biased by these facts. Stratification by CAD disease category cannot help achieve an understanding of the role of TyG in CVD. Correlations do not imply causation, so the use of the TyG index as an index in CAD patients is questionable.

  • Association of dietary glycaemic index, glycaemic load, and total carbohydrates with incidence of type-2 diabetes in adults aged ≥40 years: The Multi-Rural Communities Cohort (MRCohort)
    Diabetes Res. Clin. Pract. (IF 3.239) Pub Date : 2020-01-15
    Se Young Kim; Hye Won Woo; Young-Hoon Lee; Dong Hoon Shin; Min-Ho Shin; Bo Youl Choi; Mi Kyung Kim

    Aims To examine potential associations between the glycaemic index (GI), glycaemic load (GL), and carbohydrates and the incidence risk of type-2 diabetes (T2D) and the effect modification of obesity among Korean adults aged ≥40 years. Method Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for T2D were estimated in 8,310 participants using a modified Poisson regression model. Dietary indices were averaged using repeated dietary assessments during follow-up. Result After adjusting for potential confounders, a positive association between GI and T2D was found among women (IRR=1.63, 95% CI=1.06-2.51 in the highest tertile (T3) vs. the lowest tertile (T1) for GI, p trend=0.0310), but not for GL and carbohydrate intake. This positive association with GI was stronger in obese women (IRR=1.91, 95% CI: 1.15-3.19 in T3 vs. T1, p trend=0.0137 for body mass index ≥ 23 kg/m2; IRR=2.35, 95% CI: 1.01-5.48, p trend=0.0350 for waist circumference (WC) ≥ 85 cm). In men, there was no association before stratification by obesity, but IRRs of GI (T3 vs. T1) were significant and stronger with increased WCs (IRR=2.26, 95% CI: 1.02-4.98, p trend=0.0439 for WC ≥90). Conclusion GI may be positively associated with the incidence of T2D in women, particularly in obese women. The association of GI with T2D incidence risk may also be positive even in men with high WC.

  • Prefrontal cortex brain damage and glycemic control in patients with type 2 diabetes
    J. Diabetes (IF 3.298) Pub Date : 2020-01-14
    Sarah E. Choi; Bhaswati Roy; Matthew Freeby; Rashmi Mullur; Mary A. Woo; Rajesh Kumar

    This study examined brain tissue integrity in sites that controls cognition (prefrontal cortices; PFC) and its relationships to glycemic outcomes in adults with type 2 diabetes mellitus (T2DM).

  • Amino acids levels in early pregnancy predict subsequent gestational diabetes
    J. Diabetes (IF 3.298) Pub Date : 2020-01-14
    Rong Jiang; Shuhua Wu; Chen Fang; Chang Wang; Ya Yang; Chao Liu; Ji Hu; Yun Huang

    We aimed to estimate the performance of amino acids levels in predicting the risk of subsequent gestational diabetes mellitus (GDM).

  • Enrolment criteria for diabetes cardiovascular outcome trials do not inform on generalizability to clinical practice. The case of GLP‐1 receptor agonists
    Diabetes Obes. Metab. (IF 6.133) Pub Date : 2020-01-14
    Veronica Sciannameo; Paola Berchialla; Emanuela Orsi; Olga Lamacchia; Susanna Morano; Fabrizio Querci; Agostino Consoli; Angelo Avogaro; Gian Paolo Fadini;

    To evaluate generalizability of cardiovascular outcome trials (CVOTs) on GLP‐1 receptor agonists (GLP‐1RA), we assessed which proportion of real‐world patients with of type 2 diabetes (T2D) constitute true CVOT‐like populations.

  • MicroRNAs expression in pituitary tumors: differences related to functional status, pathological features, and clinical behavior
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-14
    T. M. Vicchio, F. Aliquò, R. M. Ruggeri, M. Ragonese, G. Giuffrida, O. R. Cotta, F. Spagnolo, M. L. Torre, A. Alibrandi, A. Asmundo, F. F. Angileri, F. Esposito, F. Polito, R. Oteri, M. H. Aguennouz, S. Cannavò, F. Ferraù

    Abstract Background MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at post-transcriptional level, having a role in many biological processes, such as control of cell proliferation, cell cycle, and cell death. Altered miRNA expression has been reported in many neoplasms, including pituitary adenomas (PAs). Purpose In this study, we aimed to evaluate the expression of 20 miRNAs involved in pathways relevant to pituitary pathophysiology, in PAs and normal pituitary tissue and to correlate their expression profile with clinical and pathological features. Methods Pituitary tumor samples were obtained during transphenoidal surgery from patients with non-functioning (NFPA, n = 12) and functioning (n = 11, 5 GH-, 3 ACTH-, 3 PRL-omas) PAs. The expression of selected miRNAs in PAs and in normal pituitary was analyzed by RT-qPCR. miRNAs expression was correlated with demographic, clinical, and neuroradiological data and with histopathological features including pituitary hormones immunostaining, Ki-67 proliferation index, and p53 immunohistochemistry evaluation. Results All evaluated miRNAs except miR-711 were expressed in both normal and tumor pituitary tissue. Seventeen miRNAs were significantly down-regulated in pituitary tumors compared to normal pituitary. miRNAs were differentially expressed in functioning PAs or in NFPAs, as in the latter group miR-149-3p (p = 0.036), miR-130a-3p (p = 0.014), and miR-370-3p (p = 0.026) were significantly under expressed as compared to functioning tumors. Point-biserial correlation analysis demonstrated a negative correlation between miR-26b-5p and Ki-67 (p = 0.031) and between miR-30a-5p and ‘atypical’ morphological features (p = 0.038) or cavernous sinus invasion (p = 0.049), while 508-5p was inversely correlated with clinical aggressiveness (p = 0.043). Conclusions In this study, we found a significant down-regulation of 17 miRNAs in PAs vs normal pituitary, with differential expression profile related to functional status and tumor aggressiveness.

  • Effects of renin–angiotensin system blockers on renal and cardiovascular outcomes in patients with diabetic nephropathy: a meta-analysis of randomized controlled trials
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-14
    X. Liu, L. Ma, Z. Li

    Abstract Purpose This study aimed to evaluate the effect f angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) on renal or cardiovascular outcomes in patients with diabetic nephropathy (DN). Methods PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) evaluating the treatment effects of ACEI and ARB on renal or cardiovascular outcomes in patients with DN until August 2017. The outcomes included end-stage renal disease (ESRD), doubling of serum creatinine levels, all-cause mortality, major cardiovascular events (MACEs), myocardial infarction (MI), stroke, and cardiac death. Relative risks (RR) with 95% confidence intervals (CIs) were used for calculating the summary results using a random-effects model. Results Twenty-four RCTs including 57,818 patients with DN and 891 events of ESRD, 1050 doubling of serum creatinine concentration, 4352 all-cause mortality, 6342 MACEs, 1073 MI, 2900 stroke, and 1674 cardiac deaths were reported. Overall, the summary results suggested that in patients with DN, receiving ACEI did not have a significant effect on ESRD, doubling of serum creatinine levels, all-cause mortality, MI, stroke, and cardiac death, while ACEI significantly reduced the risk of total MACEs. Furthermore, ARB therapy was associated with a low risk of ESRD and doubling of serum creatinine levels, while it did not differ significantly on all-cause mortality, MACEs, MI, stroke, and cardiac death in patients with DN. Conclusions Patients with DN receiving ACEI had significantly reduced the risk of total MACEs, and ARB could reduce the incidence of ESRD and the doubling of serum creatinine levels.

  • Excess BMI Accelerates Islet Autoimmunity in Older Children and Adolescents
    Diabetes Care (IF 15.270) Pub Date : 2020-01-14
    Christine Ferrara-Cook; Susan Michelle Geyer; Carmella Evans-Molina; Ingrid M. Libman; Dorothy J. Becker; Stephen E. Gitelman; Maria Jose Redondo; the Type 1 Diabetes TrialNet Study Group

    OBJECTIVE Sustained excess BMI increases the risk of type 1 diabetes (T1D) in autoantibody-positive relatives without diabetes of patients. We tested whether elevated BMI also accelerates the progression of islet autoimmunity before T1D diagnosis. RESEARCH DESIGN AND METHODS We studied 706 single autoantibody–positive pediatric TrialNet participants (ages 1.6–18.6 years at baseline). Cumulative excess BMI (ceBMI) was calculated for each participant based on longitudinally accumulated BMI ≥85th age- and sex-adjusted percentile. Recursive partitioning analysis and multivariable modeling defined the age cut point differentiating the risk for progression to multiple positive autoantibodies. RESULTS At baseline, 175 children (25%) had a BMI ≥85th percentile. ceBMI range was −9.2 to 15.6 kg/m2 (median −1.91), with ceBMI ≥0 kg/m2 corresponding to persistently elevated BMI ≥85th percentile. Younger age increased the progression to multiple autoantibodies, with age cutoff of 9 years defined by recursive partitioning analysis. Although ceBMI was not significantly associated with progression from single to multiple autoantibodies overall, there was an interaction with ceBMI ≥0 kg/m2, age, and HLA ( P = 0.009). Among children ≥9 years old without HLA DR3-DQ2 and DR4-DQ8, ceBMI ≥0 kg/m2 increased the rate of progression from single to multiple positive autoantibodies (hazard ratio 7.32, P = 0.004) and conferred a risk similar to that in those with T1D-associated HLA haplotypes. In participants <9 years old, the effect of ceBMI on progression to multiple autoantibodies was not significant regardless of HLA type. CONCLUSIONS These data support that elevated BMI may exacerbate islet autoimmunity prior to clinical T1D, particularly in children with lower risk based on age and HLA. Interventions to maintain normal BMI may prevent or delay the progression of islet autoimmunity.

  • Randomized Controlled Trial of Mobile Closed-Loop Control
    Diabetes Care (IF 15.270) Pub Date : 2020-01-14
    Boris Kovatchev; Stacey M. Anderson; Dan Raghinaru; Yogish C. Kudva; Lori M. Laffel; Carol Levy; Jordan E. Pinsker; R. Paul Wadwa; Bruce Buckingham; Francis J. Doyle; Sue A. Brown; Mei Mei Church; Vikash Dadlani; Eyal Dassau; Laya Ekhlaspour; Gregory P. Forlenza; Elvira Isganaitis; David W. Lam; John Lum; Roy W. Beck; for the iDCL Study Group

    OBJECTIVE Assess the efficacy of inControl AP: a mobile closed-loop control (CLC) system. RESEARCH DESIGN AND METHODS This protocol, [NCT02985866][1], is a 3-month parallel group, multicenter, randomized unblinded trial designed to compare mobile CLC with sensor augmented pump (SAP) therapy. Eligibility criteria were type 1 diabetes for at least 1 year, use of insulin pumps for at least 6 months, age ≥14 years, and baseline HbA1c <10.5% (91 mmol/mol). The study was designed to assess two coprimary outcomes: superiority of CLC over SAP in continuous glucose monitor (CGM)–measured time below 3.9 mmol/L and noninferiority in CGM-measured time above 10 mmol/L. RESULTS Between November 2017 and May 2018, 127 participants were randomly assigned 1:1 to CLC ( n = 65) versus SAP ( n = 62); 125 participants completed the study. CGM time below 3.9 mmol/L was 5.0% at baseline and 2.4% during follow-up in the CLC group vs. 4.7% and 4.0%, respectively, in the SAP group (mean difference −1.7% [95% CI −2.4, −1.0%]; P < 0.0001 for superiority). CGM time above 10 mmol/L was 40% at baseline and 34% during follow-up in the CLC group vs. 43% and 39%, respectively, in the SAP group (mean difference −3.0% [95% CI −6.1, +0.1%]; P < 0.0001 for noninferiority). One severe hypoglycemic event occurred in the CLC group, which was unrelated to the study device. CONCLUSIONS In meeting its coprimary end points, superiority of CLC over SAP in CGM-measured time below 3.9 mmol/L and noninferiority in CGM-measured time above 10 mmol/L, the study has demonstrated that mobile CLC is feasible and could offer certain usability advantages over embedded systems, provided the connectivity between system components is stable. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02985866&atom=%2Fdiacare%2Fearly%2F2020%2F01%2F13%2Fdc19-1310.atom

  • Association between mean platelet volume in the pathogenesis of type 2 diabetes mellitus and diabetic macrovascular complications in Japanese patients
    J. Diabetes Investig. (IF 3.902) Pub Date : 2020-01-13
    Hiroyuki Inoue; Mayumi Saito; Kumiko Kouchi; Shun‐ichiro Asahara; Fumihiko Nakamura; Yoshiaki Kido
  • Increased urocortin 3 levels are associated with the risk of having type 2 diabetes mellitus
    J. Diabetes (IF 3.298) Pub Date : 2020-01-13
    Pınar Alarslan; Gokcen Unal Kocabas; Ismail Demir; Aslı Guler; Giray Bozkaya; Behnaz Aslanipour; Mehmet Calan

    Urocortin 3 (UCN3) is a peptide hormone playing a pivotal role in glucose and lipid metabolisms. However, its clinical implications remain unclear. Our aims were to investigate the altered levels of UCN3 in newly diagnosed type 2 diabetes mellitus (nT2DM) patients in comparison to subjects with normal glucose tolerance (NGT) and to determine the presence of any possible link between UCN3 levels and metabolic parameters.

  • Trends in neurodevelopmental disability burden due to early life chemical exposure in the USA from 2001 to 2016: A population-based disease burden and cost analysis
    Mol. Cell. Endocrinol. (IF 3.693) Pub Date : 2020-01-14
    Abigail Gaylord; Gwendolyn Osborne; Akhgar Ghassabian; Julia Malits; Teresa Attina; Leonardo Trasande

    Endocrine disrupting chemicals are known to cause neurodevelopmental toxicity through direct and indirect pathways. In this study we used data from the National Health and Nutrition Examination Surveys, along with known exposure-disease relationships, to quantify the intellectual disability burden attributable to in utero exposure to polybrominated diphenyl ethers (PBDEs), organophosphates, and methylmercury and early life exposure to lead. We also estimated the cost of the IQ points lost and cases of intellectual disability. PBDE exposure was the greatest contributor to intellectual disability burden, resulting in a total of 162 million IQ points lost and over 738,000 cases of intellectual disability. This was followed by lead, organophosphates, and methylmercury. From 2001 to 2016, IQ loss from PBDEs, methylmercury, and lead have decreased or remained stagnant. Organophosphate exposure measurements were only available up to 2008 but did show an increase in organophosphate-attributable IQ loss. Although most of these trends show benefit for children's neurodevelopmental health, they may also point towards the use of potentially harmful substitutions for chemicals that are being phased out.

  • Comparison of two glucagon‐like‐peptide‐1 analogs (GLP ‐1) dulaglutide vs liraglutide for the management of diabetes in solid organ transplant (SOT): a retrospective study
    Diabetes Obes. Metab. (IF 6.133) Pub Date : 2020-01-13
    Priyamvada Singh; Maryam Taufeeq; Todd E Pesavento; Kenneth Washburn; Debbie Walsh; Shumei Meng

    GLP‐1 analog are gaining popularity in the management of diabetes in solid organ transplant recepients. There are no studies available comparing the relative effectiveness and safety of the two GLP‐1 analog Dulaglutide and Liraglutide in this population. We performed a retrospective, chart‐review of SOT‐recipients (>18 years/old) with diabetes, and on either of the agents. There was a sustained, statistically significant reduction in primary‐endpoints of weight, Body mass index (BMI), and insulin requirement in 63 SOT‐recipients at 6, 12, and 24 months respectively. A total of 59, 50, and 13 recipients were followed during 6, 12 and 24 months with the mean of paired difference for weight reduction 2.07 (p‐value < 0·003), 4.007 (p‐value < 0·001), and 5.23 kgs (p‐value <0·034) and BMI reduction of 0.80 (p‐value < 0·001), 1.35 (p‐value < 0·005) and 2·015 Kg/m2 (p‐value <0·045) respectively. The mean paired difference for insulin reduction pre, and post‐dulaglutide was 5·94 units (p‐value < 0·0002). There was no increased risk of malignancies, cardiovascular morbidity, graft‐failure or all causes mortality. Gastrointestinal (GI) manifestations were rare, it was safe even in advanced CKD patients, and required no change in immunosuppressive agents. Dulaglutide can prove to be an important option for diabetes management in SOT.

  • Increased plasma CD14 levels 1 year postpartum in women with pre-eclampsia during pregnancy: a case–control plasma proteomics study
    Nutr. Diabetes (IF 3.098) Pub Date : 2020-01-14
    Antigoni Manousopoulou; Fatma S. Abad; Diana J. Garay-Baquero; Brian R. Birch; Bas B. van Rijn; Bashir A. Lwaleed; Spiros D. Garbis
  • Two novel truncating variants of the AAAS gene causative of the triple A syndrome
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-14
    V. Vezzoli, P. Duminuco, G. Pogliaghi, M. Saccone, B. Cangiano, M. C. Rosatelli, A. Meloni, L. Persani, M. Bonomi

    The triple A syndrome (AAAS) is an inherited condition associated with mutations in the AAAS gene, which encodes a protein of 546 amino acids known as ALADIN (alacrima achalasia adrenal insufficiency neurologic disorder) whose function is not well understood. This protein belongs to the WD-repeat family of regulatory proteins and is located in the nuclear pore complexes. Only a few cohorts of AAAS patients have been reported and fully characterized. Thus, the objective of the present study was to report on a mini cohort of Italian AAAS patients and to get insights on their predisposing genetic defects.

  • Clinical characterization of patients with primary aldosteronism plus subclinical Cushing’s syndrome
    BMC Endocr. Disord. (IF 1.816) Pub Date : 2020-01-13
    Shigemitsu Yasuda; Yusuke Hikima; Yusuke Kabeya; Shinichiro Iida; Yoichi Oikawa; Masashi Isshiki; Ikuo Inoue; Akira Shimada; Mitsuhiko Noda

    Primary aldosteronism (PA) plus subclinical Cushing’s syndrome (SCS), PASCS, has occasionally been reported. We aimed to clinically characterize patients with PASCS who are poorly profiled. A population-based, retrospective, single-center, observational study was conducted in 71 patients (age, 58.2 ± 11.2 years; 24 males and 47 females) who developed PA (n = 45), SCS (n = 12), or PASCS (n = 14). The main outcome measures were the proportion of patients with diabetes mellitus (DM), serum potassium concentration, and maximum tumor diameter (MTD) on the computed tomography (CT) scans. The proportion of DM patients was significantly greater in the PASCS group than in the PA group (50.0% vs. 13.9%, p < 0.05), without a significant difference between the PASCS and SCS groups. Serum potassium concentration was significantly lower in the PASCS group than in the SCS group (3.2 ± 0.8 mEq/L vs. 4.0 ± 0.5 mEq/L; p < 0.01), without a significant difference between the PASCS and PA groups. Among the 3 study groups of patients who had a unilateral adrenal tumor, MTD was significantly greater in the PASCS group than in the PA group (2.7 ± 0.1 cm vs. 1.4 ± 0.1 cm; p < 0.001), without a significant difference between the PASCS and SCS groups. Any reference criteria were not obtained that surely distinguish patients with PASCS from those with PA or SCS. However, clinicians should suspect the presence of concurrent SCS in patients with PA when detecting a relatively large adrenal tumor on the CT scans.

  • GLUT1 expression in high-risk prostate cancer: correlation with 18 F-FDG-PET/CT and clinical outcome
    Prostate Cancer Prostatic. Dis. (IF 4.600) Pub Date : 2020-01-13
    Salma Meziou; Cassandra Ringuette Goulet; Hélène Hovington; Véronique Lefebvre; Étienne Lavallée; Michelle Bergeron; Hervé Brisson; Audrey Champagne; Bertrand Neveu; Didier Lacombe; Jean-Mathieu Beauregard; François-Alexandre Buteau; Julie Riopel; Frédéric Pouliot
  • ERRATUM FOR “Delayed Puberty—Phenotypic Diversity, Molecular Genetic Mechanisms, and Recent Discoveries”
    Endocr. Rev. (IF 15.167) Pub Date : 2020-01-11

    In the above-named article by Howard SR and Dunkel L (Endocr Rev. 2019;40(5):1285–1317; doi: 10.1210/er.2018-00248), the following error occurred during the production process of the accepted manuscript: In Table 1 “Klinefelter syndrome” under the heading “HH” should read “Kallmann syndrome.” The corrected table is shown here.

  • The Prevalence and Determinants of Cognitive Deficits and Traditional Diabetic Complications in the Severely Obese
    Diabetes Care (IF 15.270) Pub Date : 2020-01-13
    Brian C. Callaghan; Evan L. Reynolds; Mousumi Banerjee; Ericka Chant; Emily Villegas-Umana; Thomas W. Gardner; Kristen Votruba; Bruno Giordani; Rodica Pop-Busui; Subramaniam Pennathur; Eva L. Feldman

    OBJECTIVE To determine the prevalence of cognitive deficits and traditional diabetic complications and the association between metabolic factors and these outcomes. RESEARCH DESIGN AND METHODS We performed a cross-sectional study in severely obese individuals before bariatric surgery. Lean control subjects were recruited from a research website. Cognitive deficits were defined by the National Institutes of Health (NIH) Toolbox (less than the fifth percentile for lean control subjects). Cardiovascular autonomic neuropathy (CAN) was defined by an expiration-to-inspiration (E-to-I) ratio of less than the fifth percentile for lean control subjects. Retinopathy was based on retinal photographs and nephropathy on the estimated glomerular filtration rate (<60 mg/dL) and/or the albumin-to-creatinine ratio (ACR) (≥30 mg/g). NIH Toolbox, E-to-I ratio, mean deviation on frequency doubling technology testing, and ACR were used as sensitive measures of these outcomes. We used multivariable linear regression to explore associations between metabolic factors and these outcomes. RESULTS We recruited 138 severely obese individuals and 46 lean control subjects. The prevalence of cognitive deficits, CAN, retinopathy, and nephropathy were 6.5%, 4.4%, 0%, and 6.5% in lean control subjects, 22.2%, 18.2%, 0%, and 6.1% in obese participants with normoglycemia, 17.7%, 21.4%, 1.9%, and 17.9% in obese participants with prediabetes, and 25.6%, 31.9%, 6.1%, and 16.3% in obese participants with diabetes. Waist circumference was significantly associated with cognitive function (−1.48, 95% CI −2.38, −0.57) and E-to-I ratio (−0.007, 95% CI −0.012, −0.002). Prediabetes was significantly associated with retinal function (−1.78, 95% CI −3.56, −0.002). CONCLUSIONS Obesity alone is likely sufficient to cause cognitive deficits but not retinopathy or nephropathy. Central obesity is the key metabolic risk factor.

  • Intellectual Disability in KATP Channel Neonatal Diabetes
    Diabetes Care (IF 15.270) Pub Date : 2020-01-13
    Pernille Svalastoga; Åsta Sulen; Jarle R. Fehn; Stein M. Aukland; Henrik Irgens; Eivind Sirnes; Silje K.E. Fevang; Eivind Valen; Irene B. Elgen; Pål R. Njølstad

    OBJECTIVE Neonatal diabetes has been shown to be associated with high neuropsychiatric morbidity in a genotype-phenotype–dependent manner. However, the specific impact of different mutations on intellectual functioning is still insufficiently characterized. Specifically, only a small number of subjects with developmental delay have been comprehensively assessed, creating a knowledge gap for patients carrying the heaviest burden. RESEARCH DESIGN AND METHOD We here assessed the intellectual functioning and mental health of the complete Norwegian population of KATP channel neonatal diabetes. Eight sulfonylurea-treated children (five with the p.V59M genotype [ KCNJ11 ]) were assessed using age-matched control subjects with type 1 diabetes. The investigations included a physical and motor developmental examination, cerebral MRI, psychometrical examination, and questionnaires assessing intellectual capabilities and psychiatric morbidity. RESULTS A strong genotype-phenotype correlation was found, revealing the p.V59M genotype as highly associated with substantial intellectual disability, with no significant correlation with the time of sulfonylurea initiation. Consistent with previous studies, other genotypes were associated with minor cognitive impairment. Cerebral MRI verified normal brain anatomy in all but one. CONCLUSIONS We here presented a comprehensive assessment of intellectual functioning in the largest cohort of p.V59M subjects to date. The level of intellectual disability revealed not only changes the interpretation of other psychological measures but downplays a strong protective effect of sulfonylurea. Within the scope of this study, we could not find evidence supporting an early treatment start to be beneficial, although a weaker effect cannot be ruled out.

  • Effectiveness of Multidisciplinary Care Teams in Reducing Major Amputation Rate in Adults with Diabetes: A Systematic Review & Meta-Analysis
    Diabetes Res. Clin. Pract. (IF 3.239) Pub Date : 2020-01-11
    Rachel H. Albright; Nivethitha B. Manohar; Jennifer F. Murillo; Linda Anael M. Kengne; Juan J. Delgado-Hurtado; Matthew L. Diamond; Alyse L. Acciani; Adam E. Fleischer

    Aims To determine the pooled effectiveness of multidiscipinary care teams (MCTs) in reducing major amputation rates in adults with diabetes. Methods A systematic review and meta-analysis was performed, searching databases MEDLINE, EMBASE, Google Scholar, Cochrane Library, and Clinicaltrials.gov thru October 2018. We included only before-after studies comparing amputation rates before and after the implementation of a MCT for the prevention of major amputation in adults with diabetes. Our primary outcome was relative risk of major amputation. Risk ratios and 95% confidence intervals were calculated using a fixed effects model. Results Twenty studies met the inclusion criteria. Nine studies were included in the meta-analysis, and eleven were included in a qualitative analysis. Exposure to a MCT resulted in a protective effect ranging from a RR of 0.44 [p-value <0.00001 (95% CI 0.38, 0.51) I2 = 67%] to a RR of 0.61 [p-value <0.0001, (95% CI 0.50, 0.75) I2=0%] after sensitivity analysis, and remained robust in qualitative analysis. Conclusions Healthcare systems can expect a 39-56% amputation rate reduction after implementing an MCT amputation prevention program. These findings may justify the use of additional resources needed for program implementation by helping healthcare systems predict the anticipated benefit these teams have on “possible limbs saved”. Funding None

  • Simultaneous Development of Graves’ Disease and Type 1 Diabetes during Anti‐programmed Cell Death‐1 Therapy: A Case Report
    J. Diabetes Investig. (IF 3.902) Pub Date : 2020-01-11
    Susumu Kurihara; Yoichi Oikawa; Ritsuko Nakajima; Atsushi Satomura; Ryuhei Tanaka; Hiroshi Kagamu; Akira Shimada

    We present the first case of simultaneous development of Graves’ disease and type 1 diabetes during anti‐programmed cell death 1 (PD‐1) therapy. A 48‐year‐old man with parotid gland adenocarcinoma and lung metastasis had received 5 courses of nivolumab. Fourteen days after administration of the 6th course, his casual plasma glucose and hemoglobin A1c levels were 379 mg/dL and 7.2%, respectively. Moreover, thyrotoxicosis was detected with a blood test. Serum total ketone body and thyroid‐stimulating hormone receptor antibody levels increased, and serum C‐peptide level decreased to 0.01 ng/mL thereafter. Thus, we concluded that he simultaneously developed anti‐PD‐1 therapy‐associated type 1 diabetes and Graves’ disease. Among Japanese participants with autoimmune polyglandular syndrome type III, the frequency of human leukocyte antigen (HLA)‐DRB1*04:05 is higher in those with both type 1 diabetes and Graves’ disease. Our case had HLA‐DRB1*04:05, which might be associated with the simultaneous development of the two diseases.

  • nAChR signaling regulates IRE1α activation to protect β cells against terminal unfolded protein response under irremediable ER stress
    J. Diabetes Investig. (IF 3.902) Pub Date : 2020-01-10
    Tatsuya Ishibashi; Shuhei Morita; Shohei Kishimoto; Shinsuke Uraki; Ken Takeshima; Yasushi Furukawa; Hidefumi Inaba; Hiroyuki Ariyasu; Hiroshi Iwakura; Hiroto Furuta; Masahiro Nishi; Feroz R. Papa; Takashi Akamizu

    Under irremediable endoplasmic reticulum (ER) stress, hyperactivated inositol‐requiring enzyme 1α (IRE1α) triggers the terminal unfolded protein response (T‐UPR), causing crucial cell dysfunction and apoptosis. We hypothesized that nicotinic acetylcholine receptor (nAChR) signaling regulates IRE1α activation to protect β cells from the T‐UPR under ER stress.

  • American Indian young adults display diminished cardiovascular and cortisol responses to acute psychological stress
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2020-01-11
    Neha A. John-Henderson; Hannah E. Gruman; Cory J. Counts; Annie T. Ginty

    American Indian adults are at an increased risk for cardiovascular disease compared with non-Hispanic white adults. Scant research exists examining the underlying physiological and psychological mechanisms associated with these risks. This study aimed to examine possible psychological and physiological stress-related mechanisms related to cardiovascular disease risk in healthy American Indian and non-Hispanic white adults. Forty American Indian (60% female, Mean age = 19.93, SD = 2.08 years) and 45 non-Hispanic white (70% female, Mean age = 20.18, SD = 2.22 years) participants attended an in-person laboratory session. Salivary cortisol and cardiovascular activity were measured before (baseline), during, and after exposure to a 10-minute mental arithmetic task. Compared to non-Hispanic white participants, American Indian had diminished salivary cortisol (p < .001), blood pressure (p’s < .001), and heart rate (p = .041) responses to acute psychological stress. These effects could not be accounted for by differences in task performance or self-reported engagement. Previous research has shown that exaggerated responses to stress are associated with increased risk of cardiovascular disease. However, diminished responses to stress are associated with early childhood stress and future adverse behaviors (e.g., addiction, obesity). Diminished reactivity may influence behaviors that can impact future development of cardiovascular disease in American Indian populations.

  • The continuing quest for better subcutaneously administered prandial insulins: a review of recent developments and potential clinical implications
    Diabetes Obes. Metab. (IF 6.133) Pub Date : 2020-01-13
    David R. Owens; Geremia B. Bolli

    The class of rapid‐acting insulin analogues were introduced more than 20 years ago to better control postprandial plasma glucose (PPG) excursions than unmodified regular human insulin (RHI). Insulins lispro, aspart and glulisine all achieved an earlier onset of action, a greater peak effect, and shorter duration of action resulting in lower PPG levels and a reduced risk of late post‐prandial hypoglycaemia. However, the subcutaneous absorption rate of these analogues still fails to match the physiological profile of insulin in the systemic circulation following a meal. Recent reformulations of aspart and lispro have generated a second generation of more rapid‐acting insulin analogue candidates including fast‐acting aspart (faster aspart), ultra‐rapid lispro and BioChaperone lispro. These modifications have the potential to better mimic physiologic prandial insulin secretion with an even earlier onset of action with improved PPG control, a shorter duration of effect and a reduced risk of hypoglycemia. Recent phase 3 trials in type 1 and type 2 diabetes show that faster aspart and ultra‐rapid lispro compared to conventional aspart and lispro, achieved lesser PPG excursions with a small increase in post‐meal hypoglycaemia but similar or marginally superior HbA1c levels, and suggest need for parallel optimization of basal insulin replacement. Phase 1 trials for BioChaperone lispro are equally encouraging with Phase 3 trials yet to be initiated. Comparative analysis of the clinical and pharmacological evidence for these new prandial insulin candidates in the treatment of type 1 and type 2 diabetes, is the main focus of this review.

  • Primary hyperparathyroidism presenting as a brown tumor in the mandible: a case report
    BMC Endocr. Disord. (IF 1.816) Pub Date : 2020-01-13
    Bojin Xu; Jie Yu; Yingli Lu; Bing Han

    Primary hyperparathyroidism is characterized by hypercalcemia and elevated or inappropriately normal serum levels of parathyroid hormone. Brown tumor of bone is a rare non-neoplastic lesion resulted from abnormal bone metabolism in hyperparathyroidism. However, nowadays, skeletal disease caused by primary hyperparathyroidism is uncommon. We report a case of brown tumor in the mandible as the initial exhibition of primary hyperparathyroidism associated with an atypical parathyroid adenoma. The patient was a 49-year-old female, she had a pain mass on the right mandible a year ago and was treated with root canal therapy and marginal resection. After seven months, the mass recurred and enlarged. Enhanced CT scan, laboratory examination, Ultrasonography, 99mTc-MIBI SPECT-CT scintiscan and pathological examination were used to confirm the diagnosis of brown tumor. The patient’s symptom improved after parathyroidectomy. 99mTc-MIBI SPECT/CT scintigraphy is a highly sensitive examination of the localization diagnosis of hyperparathyroidism. Brown tumors should be considered in the differential diagnosis of osteolytic lesions to avoid unnecessary and harmful interventions.

  • Walkability and its association with prevalent and incident diabetes among adults in different regions of Germany: results of pooled data from five German cohorts
    BMC Endocr. Disord. (IF 1.816) Pub Date : 2020-01-13
    Nadja Kartschmit; Robynne Sutcliffe; Mark Patrick Sheldon; Susanne Moebus; Karin Halina Greiser; Saskia Hartwig; Detlef Thürkow; Ulrike Stentzel; Neeltje van den Berg; Kathrin Wolf; Werner Maier; Annette Peters; Salman Ahmed; Corinna Köhnke; Rafael Mikolajczyk; Andreas Wienke; Alexander Kluttig; Gavin Rudge

    Highly walkable neighbourhoods may increase transport-related and leisure-time physical activity and thus decrease the risk for obesity and obesity-related diseases, such as type 2 diabetes (T2D). We investigated the association between walkability and prevalent/incident T2D in a pooled sample from five German cohorts. Three walkability measures were assigned to participant’s addresses: number of transit stations, points of interest, and impedance (restrictions to walking due to absence of intersections and physical barriers) within 640 m. We estimated associations between walkability and prevalent/incident T2D with modified Poisson regressions and adjusted for education, sex, age at baseline, and cohort. Of the baseline 16,008 participants, 1256 participants had prevalent T2D. Participants free from T2D at baseline were followed over a mean of 9.2 years (SD: 3.5, minimum: 1.6, maximum: 14.8 years). Of these, 1032 participants developed T2D. The three walkability measures were not associated with T2D. The estimates pointed toward a zero effect or were within 7% relative risk increase per 1 standard deviation with 95% confidence intervals including 1. In the studied German settings, walkability differences might not explain differences in T2D.

  • Global prevalence of cardiometabolic risk factors in the military population: a systematic review and meta-analysis
    BMC Endocr. Disord. (IF 1.816) Pub Date : 2020-01-13
    Fereshteh Baygi; Kimmo Herttua; Olaf Chresten Jensen; Shirin Djalalinia; Armita Mahdavi Ghorabi; Hamid Asayesh; Mostafa Qorbani

    Although there are numerous studies on the global prevalence of cardiometabolic risk factors (CMRFs) in military personnel, the pooled prevalence of CMRFs in this population remains unclear. We aimed to systematically review the literature on the estimation of the global prevalence of CMRFs in the military population. We simultaneously searched PubMed and NLM Gateway (for MEDLINE), Institute of Scientific Information (ISI), and SCOPUS with using standard keywords. All papers published up to March 2018 were reviewed. Two independent reviewers assessed papers and extracted the data. Chi-square-based Q test was used to assess the heterogeneity of reported prevalence among studies. The overall prevalence of all CMRFs, including overweight, obesity, high low-density lipoprotein (LDL), high total cholesterol (TC), high triglyceride (TG), low high-density lipoprotein (HDL), hypertension (HTN) and high fasting blood sugar (FBS) was estimated by using the random effects meta-analysis. A total of 37 studies met the eligibility criteria and were included in the meta-analysis. According the random effect meta-analysis, the global pooled prevalence (95% confidence interval) of MetS, high LDL, high TC, high TG, low HDL and high FBS were 21% (17–25), 32% (27–36), 34% (10–57), 24% (16–31), 28% (17–38) and 9% (5–12), respectively. Moreover, global pooled prevalence of overweight, generalized obesity, abdominal obesity and HTN were estimated to be 35% (31–39), 14% (13–16), 29% (20–39) and 26 (19–34), respectively. The overall prevalence of some cardio-metabolic risk factors was estimated to be higher in military personnel. Therefore, the necessary actions should be taken to reduce risk of developing cardiovascular diseases. CRD42018103345

  • Tear inflammatory cytokines and ocular surface changes in patients with active thyroid eye disease treated with high-dose intravenous glucocorticoids
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-11
    N. Xu, Y. Cui, D. Fu, F. Sun

    To evaluate high-dose intravenous glucocorticoid treatment on tear inflammatory cytokines and ocular surface parameters in patients with active TED. Correlations between tear inflammatory cytokines and clinical parameters were also investigated.

  • Clinical features may help to identify children and adolescents with greatest risk for thyroid nodules
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-11
    N. Allen, N. Desai, C. Song, J. Yu, U. Prasad, G. Francis

    Abstract Background Thyroid nodules (TN) are detected in a small number of asymptomatic children and adolescents but are more frequently malignant (22–26%) than in adults leading some clinicians to perform thyroid ultrasound (US) for all children with goiter or autoimmune thyroiditis (AIT). Our study was designed to determine if suspicious clinical features predict the presence of TN in children with goiter or AIT so that US could be performed on those at highest risk. Methods This was a retrospective review of 223 children and adolescents with goiter or AIT evaluated at a single institution. US was not performed on all patients. It is our practice to define glands that are large, firm, or nodular to palpation as “suspicious”. Suspicious glands were interrogated by US and if TN was confirmed, this was further evaluated by fine-needle aspiration followed by surgery if indicated. Results The median age was 12.9 years with 74.4% female. TN were confirmed by US in 16.6% of all patients but only 4.8% of those with AIT. By univariate analysis, TN were more common in those with family history of TN or differentiated thyroid carcinoma (DTC), thyroid asymmetry, and lower thyrotropin (TSH) levels. Differentiated thyroid carcinoma (DTC) was identified in 10.8% of TN and 1.8% of all patients. Firmness was significantly more common in patients with DTC (p = 0.0013). Conclusion TN were less common in those with AIT than reported in previous studies, suggesting that clinical features might fail to identify the majority of TN in patients with AIT. However, patients with asymmetric thyroid and a family history of TN or DTC have greatest risk for TN.

  • 更新日期:2020-01-13
  • Sex-specific estrogen regulation of hypothalamic astrocyte estrogen receptor expression and glycogen metabolism in rats
    Mol. Cell. Endocrinol. (IF 3.693) Pub Date : 2020-01-11
    Mostafa M.H. Ibrahim; Khaggeswar Bheemanapally; Paul W. Sylvester; Karen P. Briski

    Brain astrocytes are implicated in estrogenic neuroprotection against bio-energetic insults, which may involve their glycogen energy reserve. Forebrain estrogen receptors (ER)-alpha (ERα) and -beta (ERβ) exert differential control of glycogen metabolic enzyme [glycogen synthase (GS); phosphorylase (GP)] expression in hypoglycemic male versus female rats. Studies were conducted using a rat hypothalamic astrocyte primary culture model along with selective ER agonists to investigate the premise that estradiol (E2) exerts sex-dimorphic control over astrocyte glycogen mass and metabolism. Female astrocyte GS and GP profiles are more sensitive to E2 stimulation than the male. E2 did not regulate expression of phospho-GS (inactive enzyme form) in either sex. Data also show that transmembrane G protein-coupled ER-1 (GPER) signaling is implicated in E2 control of GS profiles in each sex and alongside ERα, GP expression in females. E2 increases total 5′-AMK-activated protein kinase (AMPK) protein in female astrocytes, but stimulated pAMPK (active form) expression with equivalent potency via GPER in females and ERα in males. In female astrocytes, ERα protein was up-regulated at a lower E2 concentration and over a broader dosage range compared to males, whereas ERβ was increased after exposure to 1–10 nM versus 100 pM E2 levels in females and males, respectively. GPER profiles were stimulated by E2 in female, but not male astrocytes. E2 increased astrocyte glycogen content in female, but not male astrocytes; selective ERβ or ERα stimulation elevated glycogen levels in the female and male, respectively. Outcomes imply that dimorphic astrocyte ER and glycogen metabolic responses to E2 may reflect, in part, differential steroid induction of ER variant expression and/or regulation of post-receptor signaling in each sex.

  • The START-domain proteins in intracellular lipid transport and beyond
    Mol. Cell. Endocrinol. (IF 3.693) Pub Date : 2020-01-10
    Barbara J. Clark

    The Steroidogenic Acute Regulatory Protein-related Lipid Transfer (START) domain is a ∼210 amino acid sequence that folds into an α/β helix-grip structure forming a hydrophobic pocket for lipid binding. The helix-grip fold structure defines a large superfamily of proteins, and this review focuses on the mammalian START domain family members that include single START domain proteins with identified ligands, and larger multi-domain proteins that may have novel roles in metabolism. Much of our understanding of the mammalian START domain proteins in lipid transport and changes in metabolism has advanced through studies using knockout mouse models, although for some of these proteins the identity and/or physiological role of ligand binding remains unknown. The findings that helped define START domain lipid-binding specificity, lipid transport, and changes in metabolism are presented to highlight that fundamental questions remain regarding the biological function(s) for START domain-containing proteins.

  • Insulin resistance is associated with urinary albumin‐creatinine ratio in normal weight individuals with hypertension and diabetes: The REACTION study
    J. Diabetes (IF 3.298) Pub Date : 2020-01-10
    Shi Gu; Anping Wang; Guang Ning; Linxi Zhang; Yiming Mu

    The relationship between albuminuria and insulin resistance (IR) has not been clarified in previous studies. This study was conducted to examine whether IR is associated with albuminuria in subjects with diverse blood pressure and glycometabolism statuses.

  • TXNIP hypomethylation and its interaction with obesity and hypertriglyceridemia increase type 2 diabetes mellitus risk: a nested case‐control study
    J. Diabetes (IF 3.298) Pub Date : 2020-01-09
    Dongdong Zhang; Cheng Cheng; Meng Cao; Tieqiang Wang; Xiaoliang Chen; Yang Zhao; Bingyuan Wang; Yongcheng Ren; Dechen Liu; Leilei Liu; Xu Chen; Feiyan Liu; Qionggui Zhou; Gang Tian; Quanman Li; Chunmei Guo; Honghui Li; Jian Wang; Ruirong Cheng; Dongsheng Hu; Ming Zhang

    To estimate the T2DM incidence with DNA methylation of thioredoxin‐interacting protein gene (TXNIP) and its interaction with environmental factors.

  • Cumulative cortisol exposure increases during the academic term: Links to performance-related and social evaluative stressors
    Psychoneuroendocrinology (IF 4.013) Pub Date : 2020-01-10
    Cinnamon A. Stetler; Victoria Guinn

    Objective To examine whether cumulative cortisol production changes during a period of increased demands when cortisol and stress are assessed concurrently. The study also compared stress perceptions vs. cumulative stressful events on their respective association with cortisol output. Finally, it explored whether certain types of stressful events, those involving school/job performance or social-evaluative threat, were linked to cortisol levels across multiple weeks. Method The current study assessed cumulative cortisol production via hair sample in 56 undergraduates (88% female) during both lower stress (summer break) and higher stress (academic term) periods. During the latter, both negative events (checklist) and stress perceptions were assessed weekly, and these reports were aggregated across the 10-weeks to minimize retrospective bias. Results Cortisol levels in hair samples were significantly higher (d = 0.84) during the academic term (M = 14.24 pg/mg, SD = 11.36) compared to summer break (M = 8.00 pg/mg, SD = 4.14), suggesting greater cumulative exposure to cortisol. Although perceived stress was not associated with cortisol levels (rpartial(53) = .10, p = .46), exposure to more stressful events (rpartial(53) = .27, p = .047), particularly events involving academic demands (rpartial(53) = .37, p = .006), or negative evaluation/social rejection (rpartial(53) = .27, p = .045), was positively associated with cumulative cortisol exposure. Conclusions This study demonstrates that cortisol levels in hair may be linked to cumulative exposure to stressors when measured concurrently (3 months), and that stressful events, rather than perceptions, are reflected in HPA axis activity. Real-world stressors involving performance demands and social-evaluative threat accumulate to enhance cortisol production, consistent with their acute HPA effects in the lab. Hair samples may provide a window into the past by allowing researchers to feasibly assess cortisol production before, during, and after the onset of a chronic stressor.

  • Sodium–glucose cotransporter 2 inhibitor Dapagliflozin attenuates diabetic cardiomyopathy
    Cardiovasc. Diabetol. (IF 5.948) Pub Date : 2020-01-10
    M. Arow; M. Waldman; D. Yadin; V. Nudelman; A. Shainberg; N. G. Abraham; D. Freimark; R. Kornowski; D. Aravot; E. Hochhauser; M. Arad

    Diabetes mellitus type 2 (DM2) is a risk factor for developing heart failure but there is no specific therapy for diabetic heart disease. Sodium glucose transporter 2 inhibitors (SGLT2I) are recently developed diabetic drugs that primarily work on the kidney. Clinical data describing the cardiovascular benefits of SGLT2Is highlight the potential therapeutic benefit of these drugs in the prevention of cardiovascular events and heart failure. However, the underlying mechanism of protection remains unclear. We investigated the effect of Dapagliflozin—SGLT2I, on diabetic cardiomyopathy in a mouse model of DM2. Cardiomyopathy was induced in diabetic mice (db/db) by subcutaneous infusion of angiotensin II (ATII) for 30 days using an osmotic pump. Dapagliflozin (1.5 mg/kg/day) was administered concomitantly in drinking water. Male homozygous, 12–14 weeks old WT or db/db mice (n = 4–8/group), were used for the experiments. Isolated cardiomyocytes were exposed to glucose (17.5–33 mM) and treated with Dapagliflozin in vitro. Intracellular calcium transients were measured using a fluorescent indicator indo-1. Angiotensin II infusion induced cardiomyopathy in db/db mice, manifested by cardiac hypertrophy, myocardial fibrosis and inflammation (TNFα, TLR4). Dapagliflozin decreased blood glucose (874 ± 111 to 556 ± 57 mg/dl, p < 0.05). In addition it attenuated fibrosis and inflammation and increased the left ventricular fractional shortening in ATII treated db/db mice. In isolated cardiomyocytes Dapagliflozin decreased intracellular calcium transients, inflammation and ROS production. Finally, voltage-dependent L-type calcium channel (CACNA1C), the sodium–calcium exchanger (NCX) and the sodium–hydrogen exchanger 1 (NHE) membrane transporters expression was reduced following Dapagliflozin treatment. Dapagliflozin was cardioprotective in ATII-stressed diabetic mice. It reduced oxygen radicals, as well the activity of membrane channels related to calcium transport. The cardioprotective effect manifested by decreased fibrosis, reduced inflammation and improved systolic function. The clinical implication of our results suggest a novel pharmacologic approach for the treatment of diabetic cardiomyopathy through modulation of ion homeostasis.

  • Perimenopause, body fat, metabolism and menopausal symptoms in relation to serum markers of adiposity, inflammation and digestive metabolism
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-10
    G. Palla, C. Ramírez-Morán, M. M. Montt-Guevara, D. Salazar-Pousada, J. Shortrede, T. Simoncini, I. Grijalva-Grijalva, F. R. Pérez-López, P. Chedraui

    Perimenopausal women gain weight that may alter inflammatory status, endocrine equilibrium, and the intensity of vasomotor symptoms.

  • Glucose-Dependent Insulinotropic Polypeptide Receptor Therapies for the Treatment of Obesity, Do Agonists = Antagonists?
    Endocr. Rev. (IF 15.167) Pub Date : 2019-09-12
    Killion E, Lu S, Fort M, et al.

    Glucose-dependent insulinotropic polypeptide receptor (GIPR) is associated with obesity in human genome-wide association studies. Similarly, mouse genetic studies indicate that loss of function alleles and glucose-dependent insulinotropic polypeptide overexpression both protect from high-fat diet–induced weight gain. Together, these data provide compelling evidence to develop therapies targeting GIPR for the treatment of obesity. Further, both antagonists and agonists alone prevent weight gain, but result in remarkable weight loss when codosed or molecularly combined with glucagon-like peptide-1 analogs preclinically. Here, we review the current literature on GIPR, including biology, human and mouse genetics, and pharmacology of both agonists and antagonists, discussing the similarities and differences between the 2 approaches. Despite opposite approaches being investigated preclinically and clinically, there may be viability of both agonists and antagonists for the treatment of obesity, and we expect this area to continue to evolve with new clinical data and molecular and pharmacological analyses of GIPR function.

  • Tackling obesity in 2020—with a great resolution comes shared responsibility
    Lancet Diabetes Endocrinol. (IF 24.540) Pub Date : 2020-01-09
    The Lancet Diabetes & Endocrinology
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上海纽约大学William Glover