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Transfusion Clinique et Biologique     Full-text available via subscription   (Followers: 1, SJR: 0.396, h-index: 30)
Transfusion Medicine Reviews     Hybrid Journal   (Followers: 1, SJR: 1.821, h-index: 48)
Translational Oncology     Open Access   (SJR: 1.282, h-index: 23)
Translational Proteomics     Open Access  
Translational Research     Full-text available via subscription   (Followers: 3, SJR: 1.443, h-index: 66)
Transplant Immunology     Hybrid Journal   (Followers: 2, SJR: 0.717, h-index: 48)
Transplantation Proceedings     Hybrid Journal   (Followers: 2, SJR: 0.481, h-index: 63)
Transplantation Reviews     Hybrid Journal   (Followers: 6, SJR: 0.843, h-index: 25)
Transport Policy     Hybrid Journal   (Followers: 9, SJR: 1.666, h-index: 40)
Transportation Geotechnics     Full-text available via subscription  
Transportation Research Part A: Policy and Practice     Hybrid Journal   (Followers: 27, SJR: 2.433, h-index: 65)
Transportation Research Part B: Methodological     Hybrid Journal   (Followers: 26, SJR: 3.306, h-index: 70)
Transportation Research Part C: Emerging Technologies     Hybrid Journal   (Followers: 16, SJR: 1.943, h-index: 55)
Transportation Research Part D: Transport and Environment     Hybrid Journal   (Followers: 22, SJR: 1.255, h-index: 44)
Transportation Research Part E: Logistics and Transportation Review     Hybrid Journal   (Followers: 11, SJR: 2.155, h-index: 52)
Transportation Research Part F: Traffic Psychology and Behaviour     Hybrid Journal   (Followers: 15, SJR: 1.016, h-index: 43)
Transportation Research Procedia     Open Access  
Trastornos Adictivos     Full-text available via subscription   (Followers: 1, SJR: 0.132, h-index: 4)
Travel Behaviour and Society     Full-text available via subscription   (Followers: 1)
Travel Medicine and Infectious Disease     Hybrid Journal   (Followers: 1, SJR: 0.554, h-index: 23)
Trends in Anaesthesia and Critical Care     Full-text available via subscription   (Followers: 21, SJR: 0.148, h-index: 12)
Trends in Biochemical Sciences     Full-text available via subscription   (Followers: 20, SJR: 11.198, h-index: 210)
Trends in Biotechnology     Full-text available via subscription   (Followers: 41, SJR: 3.859, h-index: 142)
Trends in Cardiovascular Medicine     Hybrid Journal   (Followers: 4, SJR: 1.158, h-index: 74)
Trends in Cell Biology     Full-text available via subscription   (Followers: 22, SJR: 10.198, h-index: 177)
Trends in Cognitive Sciences     Full-text available via subscription   (Followers: 90, SJR: 11.395, h-index: 179)
Trends in Ecology & Evolution     Full-text available via subscription   (Followers: 146, SJR: 10.524, h-index: 214)
Trends in Endocrinology & Metabolism     Full-text available via subscription   (Followers: 13, SJR: 5.254, h-index: 108)
Trends in Environmental Analytical Chemistry     Hybrid Journal   (Followers: 1)
Trends in Food Science & Technology     Hybrid Journal   (Followers: 18, SJR: 2.189, h-index: 104)
Trends in Genetics     Full-text available via subscription   (Followers: 18, SJR: 9.354, h-index: 170)
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Trends in Pharmacological Sciences     Full-text available via subscription   (Followers: 18, SJR: 5.392, h-index: 162)
Trends in Plant Science     Full-text available via subscription   (Followers: 21, SJR: 7.209, h-index: 163)
Trials in Vaccinology     Open Access  
Tribology and Interface Engineering Series     Full-text available via subscription   (Followers: 4)
Tribology Intl.     Hybrid Journal   (Followers: 33, SJR: 1.512, h-index: 64)
Tribology Series     Full-text available via subscription   (Followers: 4)
Tsinghua Science & Technology     Full-text available via subscription   (Followers: 1, SJR: 0.179, h-index: 18)
Tuberculosis     Hybrid Journal   (Followers: 4, SJR: 1.729, h-index: 61)
Tunnelling and Underground Space Technology     Hybrid Journal   (Followers: 3, SJR: 1.687, h-index: 41)
Tzu Chi Medical J.     Full-text available via subscription   (SJR: 0.121, h-index: 7)
Ultramicroscopy     Hybrid Journal   (Followers: 2, SJR: 1.818, h-index: 80)
Ultrasonics     Hybrid Journal   (Followers: 4, SJR: 0.702, h-index: 56)
Ultrasonics Sonochemistry     Hybrid Journal   (Followers: 2, SJR: 1.469, h-index: 68)
Ultrasound Clinics     Full-text available via subscription   (Followers: 2, SJR: 0.189, h-index: 6)
Ultrasound in Medicine & Biology     Full-text available via subscription   (Followers: 6, SJR: 0.939, h-index: 91)
UMK Procedia     Open Access  
Urban Forestry & Urban Greening     Hybrid Journal   (Followers: 8, SJR: 1.482, h-index: 29)
Urologic Clinics of North America     Full-text available via subscription   (Followers: 2, SJR: 0.85, h-index: 60)
Urologic Oncology: Seminars and Original Investigations     Hybrid Journal   (Followers: 5)
Urological Science     Full-text available via subscription   (Followers: 1, SJR: 0.155, h-index: 2)
Urology     Hybrid Journal   (Followers: 49, SJR: 1.299, h-index: 136)
Urology Case Reports     Open Access  
Urology Practice     Full-text available via subscription  
Utilities Policy     Hybrid Journal   (Followers: 1, SJR: 0.546, h-index: 25)
Vaccine     Hybrid Journal   (Followers: 12, SJR: 1.715, h-index: 126)
Vacunas     Full-text available via subscription   (SJR: 0.144, h-index: 5)
Vacuum     Hybrid Journal   (Followers: 9, SJR: 0.613, h-index: 53)
Value in Health     Hybrid Journal   (Followers: 21, SJR: 1.433, h-index: 54)
Vascular Pharmacology     Hybrid Journal   (Followers: 2, SJR: 1.281, h-index: 68)
Vehicular Communications     Full-text available via subscription  
Veterinary Clinics of North America: Equine Practice     Full-text available via subscription   (Followers: 10)
Veterinary Clinics of North America: Exotic Animal Practice     Full-text available via subscription   (Followers: 9, SJR: 0.341, h-index: 20)
Veterinary Clinics of North America: Food Animal Practice     Full-text available via subscription   (Followers: 6, SJR: 0.899, h-index: 41)
Veterinary Clinics of North America: Small Animal Practice     Full-text available via subscription   (Followers: 12, SJR: 1.014, h-index: 43)
Veterinary Immunology and Immunopathology     Hybrid Journal   (Followers: 9, SJR: 0.804, h-index: 67)
Veterinary Microbiology     Hybrid Journal   (Followers: 8, SJR: 1.425, h-index: 84)
Veterinary Parasitology     Hybrid Journal   (Followers: 10, SJR: 1.229, h-index: 81)
Vibrational Spectroscopy     Hybrid Journal   (Followers: 8, SJR: 0.52, h-index: 47)
Video J. and Encyclopedia of GI Endoscopy     Open Access  
Virology     Hybrid Journal   (Followers: 15, SJR: 1.784, h-index: 135)
Virology Reports     Open Access  
Virus Research     Hybrid Journal   (Followers: 3, SJR: 1.291, h-index: 78)
Vision Research     Hybrid Journal   (Followers: 14, SJR: 1.432, h-index: 113)
Vitamins & Hormones     Full-text available via subscription   (SJR: 0.891, h-index: 52)
Waste Management     Hybrid Journal   (Followers: 14, SJR: 1.88, h-index: 71)
Waste Management Series     Full-text available via subscription   (Followers: 2)
Water Research     Hybrid Journal   (Followers: 38, SJR: 3.026, h-index: 174)
Water Resources and Economics     Hybrid Journal   (Followers: 3)
Water Resources and Industry     Open Access   (Followers: 3)
Water Resources and Rural Development     Hybrid Journal  
Water Science : The National Water Research Center J.     Open Access  
Water Science and Engineering     Open Access   (Followers: 1)
Wave Motion     Hybrid Journal   (Followers: 2, SJR: 0.675, h-index: 38)
Wavelet Analysis and Its Applications     Full-text available via subscription   (Followers: 3)
Wear     Hybrid Journal   (Followers: 21, SJR: 1.371, h-index: 92)
Weather and Climate Extremes     Open Access   (Followers: 2)
Web Semantics: Science, Services and Agents on the World Wide Web     Hybrid Journal   (Followers: 10, SJR: 2.131, h-index: 49)
Wilderness & Environmental Medicine     Hybrid Journal   (Followers: 3)
Wine Economics and Policy     Open Access   (Followers: 5)
Woman : Psychosomatic Gynaecology and Obstetrics     Hybrid Journal  
Women and Birth     Full-text available via subscription   (Followers: 7, SJR: 0.584, h-index: 13)
Women's Health Issues     Full-text available via subscription   (Followers: 6, SJR: 1.237, h-index: 35)
Women's Studies Intl. Forum     Hybrid Journal   (Followers: 2, SJR: 0.378, h-index: 29)
World Crop Pests     Full-text available via subscription   (Followers: 1)

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Journal Cover   Diabetes & Metabolism
  [SJR: 0.971]   [H-I: 62]   [51 followers]  Follow
   Full-text available via subscription Subscription journal
   ISSN (Print) 1262-3636
   Published by Elsevier Homepage  [2812 journals]
  • Lower-extremity arterial revascularization: Is there any evidence for
           diabetic foot ulcer-healing'
    • Abstract: Publication date: Available online 10 June 2015
      Source:Diabetes & Metabolism
      Author(s): J. Vouillarmet , O. Bourron , J. Gaudric , P. Lermusiaux , A. Millon , A. Hartemann
      The presence of peripheral arterial disease (PAD) is an important consideration in the management of diabetic foot ulcers. Indeed, arteriopathy is a major factor in delayed healing and the increased risk of amputation. Revascularization is commonly performed in patients with critical limb ischaemia (CLI) and diabetic foot ulcer (DFU), but also in patients with less severe arteriopathy. The ulcer-healing rate obtained after revascularization ranges from 46% to 91% at 1 year and appears to be improved compared to patients without revascularization. However, in those studies, healing was often a secondary criterion, and there was no description of the initial wound or its management. Furthermore, specific alterations associated with diabetes, such as microcirculation disorders, abnormal angiogenesis and glycation of proteins, can alter healing and the benefits of revascularization. In this review, critical assessment of data from the literature was performed on the relationship between PAD, revascularization and healing of DFUs. Also, the impact of diabetes on the effectiveness of revascularization was analyzed and potential new therapeutic targets described.

      PubDate: 2015-06-14T08:10:37Z
  • Efficacy of dual-hormone artificial pancreas to alleviate the
           carbohydrate-counting burden of type 1 diabetes: A randomized crossover
    • Abstract: Publication date: Available online 10 June 2015
      Source:Diabetes & Metabolism
      Author(s): V. Gingras , R. Rabasa-Lhoret , V. Messier , M. Ladouceur , L. Legault , A. Haidar
      Aim Carbohydrate-counting is a complex task for many patients with type 1 diabetes. This study examined whether an artificial pancreas, delivering insulin and glucagon based on glucose sensor readings, could alleviate the burden of carbohydrate-counting without degrading glucose control. Methods Twelve adults were recruited into a randomized, three-way, crossover trial ( identifier No. NCT01930097). Participants were admitted on three occasions from 7AM to 9PM and consumed a low-carbohydrate breakfast (women: 30g; men: 50g), a medium-carbohydrate dinner (women: 50g; men: 70g) and a high-carbohydrate lunch (women: 90g; men: 120g). At each visit, glucose levels were randomly regulated by: (1) conventional pump therapy; (2) an artificial pancreas (AP) accompanied by prandial boluses, matching the meal's carbohydrate content based on insulin-to-carbohydrate ratios (AP with carbohydrate-counting); or (3) an AP accompanied by prandial boluses based on qualitative categorization (regular or large) of meal size (AP without carbohydrate-counting). Results The AP without carbohydrate-counting achieved similar incremental AUC values compared with carbohydrate-counting after the low- (P =0.54) and medium- (P =0.38) carbohydrate meals, but yielded higher post-meal excursions after the high-carbohydrate meal (P =0.004). The AP with and without carbohydrate-counting yielded similar mean glucose levels (8.2±2.1mmol/L vs. 8.4±1.7mmol/L; P =0.52), and both strategies resulted in lower mean glucose compared with conventional pump therapy (9.6±2.0mmol/L; P =0.02 and P =0.03, respectively). Conclusion The AP with qualitative categorization of meal size could alleviate the burden of carbohydrate-counting without compromising glucose control, although more categories of meal sizes are probably needed to effectively control higher-carbohydrate meals.

      PubDate: 2015-06-14T08:10:37Z
  • Low bilirubin levels are an independent risk factor for diabetic
           retinopathy and nephropathy in Japanese patients with type 2 diabetes
    • Abstract: Publication date: Available online 6 June 2015
      Source:Diabetes & Metabolism
      Author(s): S. Hamamoto , H. Kaneto , S. Kamei , M. Shimoda , K. Tawaramoto , Y. Kanda-Kimura , F. Kawasaki , M. Hashiramoto , M. Matsuki , T. Mune , K. Kaku

      PubDate: 2015-06-06T07:10:22Z
  • Periaortitis induced by metformin
    • Abstract: Publication date: Available online 4 June 2015
      Source:Diabetes & Metabolism
      Author(s): H. Hamasaki , M. Hakoshima , H. Yanai

      PubDate: 2015-06-06T07:10:22Z
  • Changes in N-terminal pro-B-type natriuretic peptide and incidence of
           diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA)
    • Abstract: Publication date: Available online 3 June 2015
      Source:Diabetes & Metabolism
      Author(s): O.A. Sanchez , D.A. Duprez , H. Bahrami , C.A. Peralta , L.B. Daniels , J.A. Lima , A. Maisel , A.R. Folsom , D.R. Jacobs
      Aims This study looked at whether the inverse association of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes is modified by changes in NT-proBNP (ΔNT-proBNP) levels. Methods Plasma NT-proBNP was assayed at baseline and 3.2years later (visit 3) in the Multi-Ethnic Study of Atherosclerosis (MESA). ΔNT-proBNP was calculated as NT-proBNPvisit3 –NT-proBNPbaseline. A Poisson distribution was fitted to determine the incidence density of diabetes, adjusted for age, race, gender, educational attainment, antihypertensive medication, total intentional exercise and plasma IL-6 levels. In the primary analysis (n =3236 without diabetes up to visit 3, followed for a mean of 6.3 years), incidence density was regressed for the following categories of baseline NT-proBNP: (1)<54.4pg/mL; (2) 54.4–85.9pg/mL; and (3) 86–54.2pg/mL. This was crossed with categories of ΔNT-proBNP as medians (ranges): (1) −6.2 (−131–11.7) pg/mL; (2) 19.8 (11.8–30.1) pg/mL; (3) 44.0 (30.2–67.9) pg/mL; and (4) 111.2 (68.0–3749.9) pg/mL. Results The incidence density of diabetes followed a U-shaped association across categories of ΔNT-proBNP within categories of baseline NT-proBNP after adjusting for other covariates (P =0.02). At each level of baseline NT-proBNP, the incidence density of diabetes was lowest for small-to-moderate increases in NT-proBNP. Conclusion This analysis suggests that NT-proBNP has a biphasic association with diabetes in which the risk of incident diabetes decreases within a ‘physiological range’ of ΔNT-proBNP, and plateaus or increases as NT-proBNP concentrations increase, probably in response to pathophysiological conditions leading to high levels of NT-proBNP.

      PubDate: 2015-06-06T07:10:22Z
  • Editorial board
    • Abstract: Publication date: June 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 3

      PubDate: 2015-06-06T07:10:22Z
  • Similar glucose control with basal–bolus regimen of insulin detemir
           plus insulin aspart and thrice-daily biphasic insulin aspart 30 in
           insulin-naive patients with type 2 diabetes: Results of a 50-week
           randomized clinical trial of stepwise insulin intensification
    • Abstract: Publication date: June 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 3
      Author(s): R. Malek , F. Ajili , S.H. Assaad-Khalil , A. Shinde , J.W. Chen , E. Van den Berg
      Objective This study aimed to demonstrate the non-inferiority of 50-week treatment with stepwise insulin intensification of basal–bolus insulin analogues [insulin detemir (IDet) and aspart (IAsp)] versus biphasic insulin aspart 30 (BIAsp30) in insulin-naive type 2 diabetes mellitus (T2DM) patients not controlled by oral glucose-lowering drugs (OGLDs). Research design and methods In this open-label multicentre, multinational, randomized, parallel-arm treat-to-target trial, 403 insulin-naive patients with T2DM in four African countries were randomized to either an IDet+IAsp (n =200) or BIAsp1-2-3 (n =203) treatment group. Stepwise insulin intensification was performed at the end of 14, 26 and 38 weeks, depending on HbA1c values. The primary endpoint was change in HbA1c after 50 weeks of treatment. Safety variables were hypoglycaemia incidence, occurrence of adverse events and weight gain. Results Non-inferiority of the IDet+IAsp versus BIAsp1-2-3 treatment regimen was demonstrated by their similar HbA1c levels at the end of trial (IDet+IAsp: baseline 8.6%, 50 weeks 7.4%; BIAsp1-2-3: baseline 8.7%, 50 weeks 7.3%; full analysis set difference: 0.1% [95% CI: −0.1, 0.3]; per protocol: 0.2% [95% CI: −0.1, 0.4]). At week 50, 40.3 and 44.9% of patients achieved HbA1c <7.0% with IDet+IAsp and BIAsp1-2-3, respectively. The rate of overall hypoglycaemia during the trial was also similar in both groups (IDet+IAsp: 9.4 events/patient-year; BIAsp1-2-3: 9.8 events/patient-year). Conclusion Insulin initiation and intensification using IDet+IAsp was not inferior to BIAsp1-2-3 in insulin-naive patients with T2DM not controlled by OGLDs. Both regimens led to similar reductions in HbA1c values after 50 weeks of treatment.

      PubDate: 2015-06-06T07:10:22Z
  • Comparing kidney outcomes in type 2 diabetes treated with different
           sulphonylureas in real-life clinical practice
    • Abstract: Publication date: June 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 3
      Author(s): Y.-h. Lee , C.J. Lee , H.S. Lee , E.Y. Choe , B.-W. Lee , C.W. Ahn , B.-S. Cha , H.C. Lee , B. Balkau , E.S. Kang
      Aim Although several sulphonylureas are widely used in type 2 diabetes (T2D), their differential impacts on long-term major kidney outcomes remain unclear. This study aimed to investigate the effects of the two most commonly prescribed sulphonylureas, glimepiride and gliclazide, on kidney outcomes in patients with T2D. Methods A total of 4486 patients treated with either glimepiride or gliclazide for more than 2years were followed for up to 5.5years (median: 4.7years). A propensity score based on baseline characteristics was used to match 1427 patients treated with glimepiride with 1427 gliclazide-treated patients; incidences of end-stage renal disease (ESRD) and sustained doubling of creatinine to>132.6μmol/L (1.5mg/dL) were also compared. Results In the matched cohort with 12,122 person-years of follow-up, there was no significant difference between groups in risk of ESRD [hazard ratio (HR): 0.57, 95% confidence interval (CI): 0.29–1.12] or doubling of creatinine (HR: 0.74, 95% CI: 0.44–1.26), although there was a trend towards higher risks in the glimepiride group. Subgroup analyses showed that, compared with glimepiride, gliclazide was associated with a lower risk of doubling of creatinine in patients with preserved renal function (glomerular filtration rate≥60mL/min/1.73m2, HR: 0.21, 95% CI: 0.04–0.99) and good glycaemic control (HbA1c <7%, HR: 0.35, 95% CI: 0.14–0.86), and in older subjects (≥62years, HR: 0.52, 95% CI: 0.27–0.99). Conclusion In a real-life setting, there was no significant difference in clinical outcomes of kidney disease for patients treated with glimepiride vs gliclazide. However, gliclazide appeared to protect against renal complication progression in certain populations.

      PubDate: 2015-06-06T07:10:22Z
  • Malignant insulinoma may arise during the course of type 1 diabetes
           mellitus: A case report
    • Abstract: Publication date: June 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 3
      Author(s): S. Lablanche , M. Chobert-Bakouline , O. Risse , M.-H. Laverrière , O. Chabre , P.-Y. Benhamou

      PubDate: 2015-06-06T07:10:22Z
  • The metabolic syndrome and cancer: Is the metabolic syndrome useful for
           predicting cancer risk above and beyond its individual components'
    • Abstract: Publication date: Available online 30 May 2015
      Source:Diabetes & Metabolism
      Author(s): J. Harding , M. Sooriyakumaran , K.J. Anstey , R. Adams , B. Balkau , T. Briffa , T.M.E. Davis , W.A. Davis , A. Dobson , G.G. Giles , J. Grant , M. Knuiman , M. Luszcz , P. Mitchell , J.A. Pasco , C. Reid , D. Simmons , L. Simons , A. Tonkin , M. Woodward , J.E. Shaw , D.J. Magliano
      Aims The metabolic syndrome (MetS) is a risk factor for cancer. However, it is not known if the MetS confers a greater cancer risk than the sum of its individual components, which components drive the association, or if the MetS predicts future cancer risk. Materials and methods We linked 20,648 participants from the Australian and New Zealand Diabetes and Cancer Collaboration with complete data on the MetS to national cancer registries and used Cox proportional hazards models to estimate associations of the MetS, the number of positive MetS components, and each of the five MetS components separately with the risk for overall, colorectal, prostate and breast cancer. Hazard ratios (HR) and 95% confidence intervals (95%CI) are reported. We assessed predictive ability of the MetS using Harrell's c-statistic. Results The MetS was inversely associated with prostate cancer (HR 0.85; 95% CI 0.72-0.99). We found no evidence of an association between the MetS overall, colorectal and breast cancers. For those with five positive MetS components the HR was 1.12 (1.02-1.48) and 2.07 (1.26-3.39) for overall, and colorectal cancer, respectively, compared with those with zero positive MetS components. Greater waist circumference (WC) (1.38; 1.13-1.70) and elevated blood pressure (1.29; 1.01-1.64) were associated with colorectal cancer. Elevated WC and triglycerides were (inversely) associated with prostate cancer. MetS models were only poor to moderate discriminators for all cancer outcomes. Conclusions We show that the MetS is (inversely) associated with prostate cancer, but is not associated with overall, colorectal or breast cancer. Although, persons with five positive components of the MetS are at a 1.2 and 2.1 increased risk for overall and colorectal cancer, respectively, and these associations appear to be driven, largely, by elevated WC and BP. We also demonstrate that the MetS is only a moderate discriminator of cancer risk.

      PubDate: 2015-06-06T07:10:22Z
  • Liraglutide in whole-pancreas transplant patients with impaired glucose
           homoeostasis: A case series
    • Abstract: Publication date: June 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 3
      Author(s): B. Cariou , C. Bernard , D. Cantarovich
      Hyperglycaemia may develop after whole-pancreas transplantation (PTX) in patients with type 1 diabetes mellitus (T1DM), but the efficacy and tolerability of GLP-1 receptor agonists have not been assessed in this population. This report is a 6-month prospective follow-up of six T1DM recipients of PTX (mean time after PTX: 68.8±45.7 months), all of whom had an HbA1c >6.5% (48mmol/mol) [mean: 7.1% (54mmol/mol)] after initiation of liraglutide alone at 0.6mg once daily titrated to 1.2mg once daily at week 1. Gastrointestinal disorders were reported in three of the six patients, with discontinuation of liraglutide in only one patient. HbA1c improved in the five remaining patients, with a median decrease of 0.8% (0.0–2.7%) at 6 months, and the median decrease in body weight was 2.0kg. Immunosuppressive treatments remained unchanged with liraglutide. Thus, liraglutide appears to be an effective and well-tolerated option in PTX patients with impaired glucose homoeostasis, regardless of the cause.

      PubDate: 2015-06-06T07:10:22Z
  • Increased TSH in obesity: Evidence for a BMI-independent association with
    • Abstract: Publication date: June 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 3
      Author(s): C. Bétry , M.A. Challan-Belval , A. Bernard , A. Charrié , J. Drai , M. Laville , C. Thivolet , E. Disse
      Aim This study aimed to determine whether the association between thyroid-stimulating hormone (TSH) and body mass index (BMI) is related to leptin concentration in obese individuals. Methods Plasma TSH and leptin assays were performed in 800 consecutive patients, hospitalized for a nutritional checkup, with a BMI≥30kg/m2. Various anthropometric, hormonal and metabolic parameters, including age, weight, BMI, insulin, leptin and TSH, were measured or calculated. Univariate and multivariate regression analyses were performed to identify any significant relationships between these parameters. Also, characteristics of the patients in the lowest and highest quartiles of TSH distribution were compared. Results TSH was positively correlated with both BMI and leptin. When multiple regression analysis was performed, TSH and leptin maintained a significant association independent of BMI. Patients in the fourth quartile of TSH distribution displayed higher BMI and higher leptin levels in comparison to the first quartile. Conclusion Our study has confirmed an increase in TSH in conjunction with BMI in obese subjects. This increase was correlated with leptin independently of BMI. It is hypothesized that the increase in TSH observed in obese subjects was the consequence of both fat mass accumulation and a positive energy-balance.

      PubDate: 2015-06-06T07:10:22Z
  • Efficacy of vildagliptin and sitagliptin in lowering fasting plasma
           glucose: Results of a randomized controlled trial
    • Abstract: Publication date: June 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 3
      Author(s): R. Göke , P. Eschenbach , E.D. Dütting
      Aim This study compared the efficacy of vildagliptin and sitagliptin in lowering fasting plasma glucose (FPG) as single-pill combinations (SPCs) with metformin. Methods The randomized crossover, open-label, active-controlled study design assessed the FPG-lowering abilities of a vildagliptin/metformin (50/1000mg twice daily) SPC compared with a sitagliptin/metformin (50/1000mg twice daily) SPC after 2 weeks of treatment in 99 type 2 diabetes patients uncontrolled by stable metformin therapy (1000–2000mg/day). Results The change in FPG from baseline to day 14 was significantly greater (P <0.02, Wilcoxon) with vildagliptin [–21.9mg/dL (SD 27.0)] than with sitagliptin [–14.5mg/dL (SD 23.0)]. After 14 days of treatment, the mean FPG was 137.8mg/dL (SD 28.5) with vildagliptin and 140.1mg/dL (SD 26.5) with sitagliptin (P <0.05, Wilcoxon). Conclusion Both of these DPP-4 inhibitors, given as SPCs twice daily with metformin, lowered FPG after 14 days of treatment. However, vildagliptin produced a significantly greater reduction in FPG vs baseline compared with sitagliptin, which may translate into clinical relevance.

      PubDate: 2015-06-06T07:10:22Z
  • Screening for dysglycaemia during pregnancy: Proposals conciliating
           International Association of Diabetes and Pregnancy Study Group (IADPSG)
           and US National Institutes of Health (NIH) panels
    • Abstract: Publication date: June 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 3
      Author(s): E. Cosson , P. Valensi , L. Carbillon
      The International Association of Diabetes and Pregnancy Study Group (IADPSG) has proposed that blood glucose levels for the diagnosis of gestational diabetes mellitus (GDM) be the values associated with a 1.75-fold increase in the risk of neonatal complications in the Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) study. However, this recommendation was not adopted by the US National Institutes of Health (NIH) panel as it would have been responsible for a huge increase in the prevalence of GDM with no clear evidence of a reduction of events at such blood glucose values. Considering this aspect, we now propose the use of a blood glucose threshold combination associated with an odds-ratio of 2.0 for neonatal disorders [fasting plasma glucose (FPG)≥95mg/dL, or a 1-h glucose value after a 75-g oral glucose tolerance test (OGTT)≥191mg/dL or a 2-h glucose value≥162mg/dL] for GDM diagnosis. This would lead to a lower prevalence of GDM and concentrate medical resources on those with the highest risk of complications. This would also allow the use of a similar FPG value for both the diagnosis and therapeutic target of GDM. The IADPSG also proposed screening for dysglycaemia during early pregnancy, using FPG measurement with a similar threshold after 24 weeks of gestation. We propose the same strategy considering an FPG value≥95mg/dL as abnormal, but only after confirmatory measurements. We also believe that an OGTT should not be used before 24 weeks of gestation as normal values during that time are as yet unknown.

      PubDate: 2015-06-06T07:10:22Z
  • Association between thyroid hormones, thyroid antibodies and insulin
           resistance in euthyroid individuals: A population-based cohort
    • Abstract: Publication date: Available online 3 June 2015
      Source:Diabetes & Metabolism
      Author(s): A. Amouzegar , E. Kazemian , S. Gharibzadeh , L. Mehran , M. Tohidi , F. Azizi
      Aim The association between insulin resistance and thyroid function in euthyroid subjects has not yet been clarified. This study aimed to investigate the association between thyroid function within the normal reference range and insulin resistance in participants of the Tehran Thyroid Study (TTS). Methods This cross-sectional study was conducted within the framework of the TTS. Of 5786subjects aged≥20 years, 2758euthyroid subjects free of thyroid disorders, diabetes, chronic kidney disease and cardiovascular disease, and not taking steroids and lipid-lowering agents, were included. Serum concentrations of free thyroxine (FT4) and TSH were measured. The homoeostasis model assessment index for insulin resistance (HOMA-IR) was used to evaluate IR. Results On linear regression analysis, a negative association was found between serum FT4 levels and HOMA-IR in the model with age, smoking and physical activity (B=−0.09, P <0.001) and in the WC-adjusted model with age, smoking and physical activity for men (B=−0.06, P <0.01). In addition, there was a positive association between serum TSH levels and HOMA-IR in both models [with age, smoking and physical activity (B=0.07, P =0.006), and age, smoking, physical activity and adjusted for WC (B=0.05, P =0.01)] that was not more significant on logistic regression analysis. In women, neither serum FT4 nor TSH levels were associated with HOMA-IR; the prevalence of IR decreased from 27.2 to 19.1 with increasing tertiles of FT4 only in men (P =0.01). No significant differences were observed in HOMA-IR and its components between thyroid peroxidase antibody (TPOAb)-negative and -positive groups. Also, it was found that metabolically healthy but obese (MHO) subjects had higher levels of TSH than individuals who were MONW (metabolically obese but normal weight; P <0.01). Conclusion Low FT4 was independently associated with IR in healthy euthyroid Iranian men.

      PubDate: 2015-06-06T07:10:22Z
  • Determinants of changes in muscle mass after bariatric surgery
    • Abstract: Publication date: Available online 26 May 2015
      Source:Diabetes & Metabolism
      Author(s): C. Vaurs , C. Diméglio , L. Charras , Y. Anduze , M. Chalret du Rieu , P. Ritz
      Aim The constituents of weight loss following bariatric surgery are poorly known. There is an expectation of a limited loss of lean body mass (LBM), and a significant loss of fat mass (FM) as well as muscle mass (MM), which could lead to functional loss and metabolic impairment. This prospective study analysed the determinants of MM changes after Roux-en-Y gastric bypass and sleeve gastrectomy. Methods The study cohort comprised 114 consecutive candidates for bariatric surgery referred to a bariatric surgery centre. Using DEXA, the subjects’ body composition was assessed before, and three and 12 months (n =92) after, the surgery, along with their biological status. The main study outcome was changes in MM. Results At three months, patients had lost 20.3kg, made up of 41% LBM and 59% FM. The contribution of MM to weight loss was 16.4%. Cluster analysis showed that 52 patients lost<15% of their weight as MM, while 62 patients lost>15% as MM. At 12 months, patients had lost 37kg, made up of 70% FM and 30% LBM. At this time, only 27 patients lost>15% of their weight as MM. The determinants that were negatively and independently associated with MM changes at three months were FM loss and changes in glycaemia and thyroid-stimulating hormone ([TSH]; thyrotropin) before surgery, whereas change in glycaemia was the only 12-month determinant associated with MM changes. Conclusion Two phenotypes – one with muscle wasting and the other with acceptable muscle loss – with a threshold of 15% and very few predictive factors were identified by this study.

      PubDate: 2015-05-30T07:04:23Z
  • Treatment maintenance duration of dual therapy with metformin and
           sitagliptin in type 2 diabetes: The ODYSSEE observational study
    • Abstract: Publication date: Available online 12 May 2015
      Source:Diabetes & Metabolism
      Author(s): P. Valensi , G. de Pouvourville , N. Benard , C. Chanut-Vogel , C. Kempf , E. Eymard , C. Moisan , J. Dallongeville
      Aim The study compared the duration of maintenance of treatment in patients with type 2 diabetes (T2D) using dual therapy with either metformin and sitagliptin (M-Sita) or metformin and a sulphonylurea (M-SU). Materials and methods This observational study included adult patients with T2D who had responded inadequately to metformin monotherapy and therefore had started de-novo treatment with Met-Sita or Met-SU within the previous eight weeks. Patient follow-up and changes to treatment were performed according to their general practitioner's usual clinical practice. The primary outcome was time to change in treatment for whatever cause. HbA1c and symptomatic hypoglycaemia were also documented. Results The median treatment duration for patients in the M-Sita group (43.2 months) was significantly longer (P <0.0001) than in the M-SU group (20.2 months). This difference persisted after adjusting for baseline differences and confounders. A similar reduction in HbA1c was noted in both arms (–0.6%), and the incidence of hypoglycaemia prior to treatment modification was lower with M-Sita (9.7%) than with M-SU (21.0%). Adverse events potentially related to treatment were reported in 2.8% (n =52) and 2.7% (n =20) of patients in the M-Sita and M-SU arms, respectively. Conclusion Under everyday conditions of primary diabetes care, dual therapy with M-Sita can be maintained for longer than M-SU. In addition, while efficacy, as measured by changes in HbA1c, was similar between treatments, the incidence of hypoglycaemia was lower in patients taking M-Sita.

      PubDate: 2015-05-13T06:48:37Z
  • Is HbA1c a valid surrogate for macrovascular and microvascular
           complications in type 2 diabetes'
    • Abstract: Publication date: Available online 6 May 2015
      Source:Diabetes & Metabolism
      Author(s): T. Bejan-Angoulvant , C. Cornu , P. Archambault , B. Tudrej , P. Audier , Y. Brabant , F. Gueyffier , R. Boussageon
      Recent recommendations regarding type 2 diabetes (T2D) patients’ treatments have focused on personalizing glycosylated haemoglobin (HbA1c) targets. Because the relationship between HbA1c and diabetes prognosis has been established from large prospective cohorts, it is valid to question the extrapolation from population-based risk reduction estimations to individual predictions. Our study aimed to investigate the relationship between HbA1c reductions and clinical outcomes in randomized controlled trials (RCTs), using a meta-regression approach. Included were RCTs comparing intensive vs. standard glucose-lowering regimens for cardiovascular events and microvascular complications in T2D patients. Eight studies (33,396 patients) providing data for HbA1c reductions were found. In our meta-regression, HbA1c decreases were not significantly associated with reductions in our main study outcomes: total and cardiovascular mortality. They were also not associated with any of the secondary endpoints, including myocardial infarction, stroke and severe hypoglycaemia. Sensitivity analysis showed a significant correlation only between HbA1c-lowering and severe hypoglycaemia (P =0.014). Meta-regression analysis could find no significant association between HbA1c-lowering and a decrease in clinical outcomes, thereby questioning the use of HbA1c as a surrogate outcome for T2D-related complications. Thus, RCTs vs. placebo are urgently required to evaluate the risk–benefit ratios of therapeutic strategies beyond HbA1c control in T2D patients.

      PubDate: 2015-05-09T06:44:17Z
  • Intracellular diglycerides in relation to glycaemic control in the
           myocardium: A pilot study in humans
    • Abstract: Publication date: Available online 5 May 2015
      Source:Diabetes & Metabolism
      Author(s): C.A. Anastasiou , A. Stamatelopoulos , P. Dedeilias , C. Charitos , L.S. Sidossis , S.A. Kavouras
      Aim Intramyocellular diglycerides have been implicated in the development of insulin resistance in skeletal muscle. In the myocardium, excess lipid storage may also contribute to the appearance of diabetic cardiomyopathy, while diglycerides may have certain cardio-protective functions. However, little is known on intracellular diglyceride accumulation in the human heart. We aimed to determine diglyceride accumulation in the human myocardium in relation to diabetes status. Methods Six diabetic and six non-diabetic aged human subjects undergoing by-pass surgery participated in the study. Subjects were matched for age and body mass index. Intracellular diglyceride levels were measured in heart biopsy samples. Additional samples were taken from pectoralis major muscle that served as control. Whole body glycaemic control was assessed as the percent glycated haemoglobin. Results Intracellular diglycerides were significantly higher in the myocardium compared to pectoralis major (P <0.05). Although not statistically significant, diabetic subjects tended to accumulate smaller amounts of diglycerides compared to non-diabetic subjects in the myocardium. A linear negative correlation was observed between myocardial diglycerides and glycaemic control (r =0.632, P <0.05). Conclusions Our data suggest that poor glycaemic control and diabetes may be associated with a defective accumulation of myocardial diglycerides, possibly blunting intracellular processes and contributing to the development of cardiomyopathy.

      PubDate: 2015-05-09T06:44:17Z
  • Oral magnesium supplementation improves glycaemic status in subjects with
           prediabetes and hypomagnesaemia: A double-blind placebo-controlled
           randomized trial
    • Abstract: Publication date: Available online 27 April 2015
      Source:Diabetes & Metabolism
      Author(s): F. Guerrero-Romero , L.E. Simental-Mendía , G. Hernández-Ronquillo , M. Rodriguez-Morán
      Aim This study evaluated the efficacy of oral magnesium supplementation in the reduction of plasma glucose levels in adults with prediabetes and hypomagnesaemia. Methods A total of 116 men and non-pregnant women, aged 30 to 65years with hypomagnesaemia and newly diagnosed with prediabetes, were enrolled into a randomized double-blind placebo-controlled trial to receive either 30mL of MgCl2 5% solution (equivalent to 382mg of magnesium) or an inert placebo solution once daily for four months. The primary trial endpoint was the efficacy of magnesium supplementation in reducing plasma glucose levels. Results At baseline, there were no significant statistical differences in terms of anthropometric and biochemical variables between individuals in the supplement and placebo groups. At the end of follow-up, fasting (86.9±7.9 and 98.3±4.6mg/dL, respectively; P =0.004) and post-load glucose (124.7±33.4 and 136.7±23.9mg/dL, respectively; P =0.03) levels, HOMA-IR indices (2.85±1.0 and 4.1±2.7, respectively; P =0.04) and triglycerides (166.4±90.6 and 227.0±89.7, respectively; P =0.009) were significantly decreased, whereas HDL cholesterol (45.6±10.9 and 46.8±9.2mg/dL, respectively; P =0.04) and serum magnesium (1.96±0.27 and 1.60±0.26mg/dL, respectively; P =0.005) levels were significantly increased in those taking MgCl2 compared with the controls. A total of 34 (29.4%) people improved their glucose status (50.8% and 7.0% in the magnesium and placebo groups, respectively; P <0.0005). Conclusion Our results show that magnesium supplementation reduces plasma glucose levels, and improves the glycaemic status of adults with prediabetes and hypomagnesaemia.

      PubDate: 2015-05-01T06:34:35Z
  • Different associations of body mass index and visceral fat area with
           metabolic parameters and adipokines in Japanese patients with type 2
    • Abstract: Publication date: Available online 25 April 2015
      Source:Diabetes & Metabolism
      Author(s): H. Yanai , Y. Hirowatari

      PubDate: 2015-04-27T06:17:29Z
  • A novel heterozygous mutation in the glucokinase gene is responsible for
           an early-onset mild form of maturity-onset diabetes of the young, type 2
    • Abstract: Publication date: Available online 25 April 2015
      Source:Diabetes & Metabolism
      Author(s): D.T. Papadimitriou , P.J. Willems , C. Bothou , T. Karpathios , A. Papadimitriou

      PubDate: 2015-04-27T06:17:29Z
  • MicroRNAs and the functional β cell mass: For better or worse
    • Abstract: Publication date: Available online 22 April 2015
      Source:Diabetes & Metabolism
      Author(s): C. Guay , R. Regazzi
      Insulin secretion from pancreatic β cells plays a central role in the control of blood glucose levels. The amount of insulin released by β cells is precisely adjusted to match organism requirements. A number of conditions that arise during life, including pregnancy and obesity, can result in a decreased sensitivity of insulin target tissues and a consequent rise in insulin needs. To preserve glucose homoeostasis, the augmented insulin demand requires a compensatory expansion of the pancreatic β cell mass and an increase in its secretory activity. This compensatory process is accompanied by modifications in β cell gene expression, although the molecular mechanisms underlying the phenomenon are still poorly understood. Emerging evidence indicates that at least part of these compensatory events may be orchestrated by changes in the level of a novel class of gene regulators, the microRNAs. Indeed, several of these small, non-coding RNAs have either positive or negative impacts on β cell proliferation and survival. The studies reviewed here suggest that the balance between the actions of these two groups of microRNAs, which have opposing functional effects, can determine whether β cells expand sufficiently to maintain blood glucose levels in the normal range or fail to meet insulin demand and thus lead, as a consequence, towards diabetes manifestation. A better understanding of the mechanisms governing changes in the microRNA profile will open the way for the development of new strategies to prevent and/or treat both type 2 and gestational diabetes.

      PubDate: 2015-04-23T06:13:35Z
  • Lower serum zinc levels are associated with unhealthy metabolic status in
           normal-weight adults: The 2010 Korea National Health and Nutrition
           Examination Survey
    • Abstract: Publication date: Available online 20 April 2015
      Source:Diabetes & Metabolism
      Author(s): H.K. Yang , S.H. Lee , K. Han , B. Kang , S.Y. Lee , K.H. Yoon , H.S. Kwon , Y.M. Park
      Aim This study investigated whether serum zinc concentration is associated with glucose tolerance, insulin resistance and metabolic health status in Korean adults. Methods Subjects with available serum zinc levels were recruited from the fifth Korea National Health and Nutrition Examination Survey (KNHANESV) cohort. Those in the highest quartile on homoeostasis model assessment for insulin resistance (HOMA-IR) and with a body mass index (BMI) of 18.5–25kg/m2 were classified as metabolically obese and normal weight (MONW). Results A total of 1813 subjects with a mean age of 45.2±0.5 years and a mean BMI of 24.01±0.11kg/m2 were enrolled. Those in the lower serum zinc quartiles exhibited higher levels of fasting blood glucose and insulin resistance indices compared with those in the higher quartiles. However, these associations were positive only in normal-weight subjects. Those categorized as MONW exhibited significantly lower serum zinc levels than the metabolically healthy and normal weight (MHNW) subjects (131.6±3.0μg/dL vs 141.7±2.8μg/dL, respectively; P =0.0026), whereas serum zinc levels did not differ according to metabolic health in obese subjects. The odds ratio for being categorized as MONW was 4.12 (95% CI: 1.75, 9.72) among those in the lowest serum zinc quartile compared with those in the highest quartile even after adjusting for possible confounding factors. Conclusion Lower serum zinc levels were associated with unhealthy metabolic status in normal-weight adults. Further prospective studies are required to define the role of zinc in metabolic health.

      PubDate: 2015-04-23T06:13:35Z
  • Using the respective contributions of postprandial and basal glucose for
           tailoring treatments in type 2 diabetes
    • Abstract: Publication date: Available online 17 April 2015
      Source:Diabetes & Metabolism
      Author(s): L. Monnier , C. Colette

      PubDate: 2015-04-18T05:29:25Z
  • Individualizing treatment of type 2 diabetes by targeting postprandial or
           fasting hyperglycaemia: Response to a basal vs a premixed insulin regimen
           by HbA1c quartiles and ethnicity
    • Abstract: Publication date: Available online 14 April 2015
      Source:Diabetes & Metabolism
      Author(s): A.J. Scheen , H. Schmitt , H.H. Jiang , T. Ivanyi
      Aim This study evaluated the proportions of prandial (PHG) vs fasting hyperglycaemia (FHG) over 24h in a group of patients with type 2 diabetes (overall and for Caucasian vs Asian patients), and tested the hypothesis that an insulin regimen with a prandial component allows a greater response than basal insulin at low glycated haemoglobin (HbA1c) levels with a higher proportion of PHG than FHG. Methods Relative contributions of PHG and FHG to overall hyperglycaemia were analyzed by baseline HbA1c quartiles and by ethnicity at baseline and after 24-week treatment with either insulin glargine or insulin lispro mix 25 in the DURABLE study. Results With increasing baseline HbA1c, the mean relative contribution of PHG to the total area under the curve decreased (from 41% to 27%) while FHG was increased (from 59% to 73%). Both insulins decreased FHG, but only insulin lispro mix 25 decreased PHG. More patients with baseline HbA1c <9%, where PHG was more relevant, achieved the target HbA1c of<7% at endpoint with insulin lispro mix 25 compared with glargine. On average, Asians had a 10% larger contribution of PHG at all HbA1c quartiles, and a lower proportion of Asians reached the HbA1c target of<7% with either insulin treatment compared with Caucasians. Conclusion At baseline, the contribution of FHG to overall hyperglycaemia predominated at all HbA1c quartiles, whereas PHG was more clinically relevant at lower HbA1c levels and with a greater response to insulin lispro mix 25. Asians had a greater proportion of PHG and a lesser response to either insulins compared with Caucasians. Thus, responses to diabetes drugs by baseline HbA1c and ethnicity are worth investigating to better target and individualize treatment.

      PubDate: 2015-04-18T05:29:25Z
  • Are third-trimester adipokines associated with higher metabolic risk among
           women with gestational diabetes'
    • Abstract: Publication date: Available online 15 April 2015
      Source:Diabetes & Metabolism
      Author(s): D. Honnorat , E. Disse , L. Millot , E. Mathiotte , M. Claret , A. Charrie , J. Drai , L. Garnier , C. Maurice , E. Durand , C. Simon , O. Dupuis , C. Thivolet
      Aim This study aimed to determine whether third-trimester adipokines during gestational diabetes (GDM) are associated with higher metabolic risk. Methods A total of 221 women with GDM (according to IADPSG criteria) were enrolled between 2011/11 and 2013/6 into a prospective observational study (IMAGE), and categorized as having elevated fasting blood glucose (FBG) or impaired fasting glucose (IFG, n =36) if levels were≥92mg/dL during a 75-g oral glucose tolerance test (OGTT), impaired glucose tolerance (IGT, n =116) if FBG was<92mg/dL but with elevated 1-h or 2-h OGTT values, or impaired fasting and stimulated blood glucose (IFSG, n =69) if both FBG was≥92mg/dL and 1-h or 2-h OGTT values were elevated. Results Pre-gestational body mass index (BMI) was higher in women with IFG or IFSG compared with IGT (P <0.001), as were leptin levels in women with IFG vs IGT [34.7 (10.5–119.7) vs 26.6 (3.56–79.4) ng/L; P =0.008]. HOMA2-IR scores were higher in women with IFG or IFSG vs IGT (1.87±1.2 or 1.72±0.9 vs 1.18±0.8, respectively; P <0.001). Also, those with IFSG vs those with IGT had significantly lower HOMA2-B scores (111.4±41.3 vs 127.1±61.6, respectively; P <0.05) and adiponectin levels [5.00 (1.11–11.3) vs 6.19 (2.11–17.7) μg/mL; P <0.001], and higher levels of IL-6 [1.14 (0.33–20.0) vs 0.90 (0.31–19.0); P =0.012] and TNF-α [0.99 (0.50–10.5) vs 0.84 (0.45–11.5) pg/mL; P =0.003]. After adjusting for age, parity, and pre-gestational and gestational BMI, the difference in adiponectin levels remained significant. Conclusion Diagnosing GDM by IADSPG criteria results in a wide range of heterogeneity. Our study has indicated that adipokine levels in addition to FBG may help to select women at high metabolic risk for appropriate monitoring and post-delivery interventions ( number NCP02133729).

      PubDate: 2015-04-18T05:29:25Z
  • Active and passive exposure to tobacco smoke in relation to insulin
           sensitivity and pancreatic β-cell function in Japanese subjects
    • Abstract: Publication date: April 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 2
      Author(s): S. Oba , E. Suzuki , M. Yamamoto , Y. Horikawa , C. Nagata , J. Takeda
      Aim Several studies have suggested that cigarette-smoking affects insulin sensitivity in Western populations. The present study evaluated glucose tolerance, pancreatic β-cell function and insulin sensitivity in relation to active and passive smoking among the Japanese. Methods A total of 411 men and 586 women were recruited into a community-based cross-sectional study in Gifu, Japan. Diabetes, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were screened for by a 75g oral glucose tolerance test. HOMA and insulinogenic (ΔI0−30/ΔG0−30) indexes were used to estimate insulin secretion and sensitivity. To assess the possible association of self-reported smoking status and parameters of glucose metabolism, logistic regression was applied after adjusting for potential confounders. Results Currently smoking women were more likely to have diabetes, IGT or IFG compared with never-smoking women (OR: 2.26, 95% CI: 1.05–4.84). Heavy-smoking men (≥25 cigarettes/day) were likely to be in the lowest tertile group of ΔI0–30/ΔG0–30 compared with never-smoking men (OR: 2.64, 95% CI: 1.05–6.68, P trend =0.04). The number of cigarettes/day was borderline significantly associated with diabetes in men. Also with borderline significance, never-smoking women with smoking husbands were more likely to have diabetes, IGT or IFG (OR: 1.62, 95% CI: 1.00–2.62) and significantly more likely to have lower HOMA-β (OR: 2.17, 95% CI: 1.36–3.48) than those without smoking husbands. Conclusion The greater the number of cigarettes smoked per day appears to be associated with diabetes among men whereas, among women, both active and passive smoking appear to be associated with diabetic states, including IGT and IFG. An association between smoking status and insulin secretion is also suggested, whereas no significant association was observed with HOMA-IR in this Japanese subjects, suggesting that the influence of smoking on glucose metabolism may differ among races.

      PubDate: 2015-04-14T04:12:24Z
  • Effects of alcohol consumption and the metabolic syndrome on 10-year
           incidence of diabetes: The ATTICA study
    • Abstract: Publication date: April 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 2
      Author(s): E. Koloverou , D.B. Panagiotakos , C. Pitsavos , C. Chrysohoou , E.N. Georgousopoulou , V. Metaxa , C. Stefanadis
      Aim The purpose of this prospective study was to investigate the effect of alcohol consumption on the 10-year diabetes incidence. Methods In 2001–2002, a random sample of 1514 men (18–89 years old) and 1528 women (18–87 years old) was selected to participate in the ATTICA study (Athens metropolitan area, Greece). Among various other characteristics, average daily alcohol intakes (abstention, low, moderate, high) and type of alcoholic drink were evaluated. Diabetes was defined according to American Diabetes Association criteria. During 2011–2012, the 10-year follow-up was performed. Results The 10-year incidence of diabetes was 13.4% in men and 12.4% in women. After making various adjustments, those who consumed up to 1 glass/day of alcohol had a 53% lower diabetes risk (RR=0.47; 95% CI: 0.26, 0.83) compared with abstainers, while trend analysis revealed a significant U-shaped relationship between quantity of alcohol drunk and diabetes incidence (P <0.001 for trend). Specific types of drinks were not associated with diabetes incidence; however, a one-unit increase in ratio of wine/beer/vodka vs. other spirits was associated with an 89% lower risk of diabetes (RR=0.11; 95% CI: 0.02, 0.67). The protective effect of low alcohol consumption on diabetes incidence was more prominent among individuals with stricter adherence to the Mediterranean diet (RR=0.08; 95% CI: 0.011, 0.70) and without the metabolic syndrome (RR=0.34; 95% CI: 0.16, 0.70). Conclusion This work revealed the protective effect of modest alcohol consumption of particularly wine and beer against the long-term incidence of diabetes, possibly due to their pleiotropic health effects.

      PubDate: 2015-04-14T04:12:24Z
  • Adverse drug reaction: A possible case of glimepiride-induced syndrome of
           inappropriate antidiuretic hormone secretion
    • Abstract: Publication date: April 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 2
      Author(s): H. Adachi , H. Yanai

      PubDate: 2015-04-14T04:12:24Z
  • More effective glycaemic control by metformin in African Americans than in
           Whites in the prediabetic population
    • Abstract: Publication date: April 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 2
      Author(s): C. Zhang , R. Zhang
      Aim Metformin, a first-line diabetes drug, delays the onset of type 2 diabetes in the prediabetic population; however, in prediabetic patients, differences in glycaemic response to metformin among racial groups are unknown. We aimed to compare glucose-lowering effects of metformin between Whites and African Americans (AAs). Methods We performed a secondary analysis using data from the diabetes prevention program, a multi-center randomized clinical trial, in which all participants were prediabetic. The metformin group (582 Whites and 210 AAs) received 850mg of metformin twice daily, and was followed for 3years. Results We found that after 6months on metformin, Whites had a drop of 3.89±0.39 (mg/dL, mean±SEM) in the fasting plasma glucose level, significantly less than that in African Americans (6.04±0.72, P =0.006); at years 1 and 2, the differences were also significant. Consistently, the linear mixed model showed that, within 1year of metformin treatment, the rate in reduction of glucose levels was more pronounced in AAs than in Whites (P =0.025 following adjustment for age and sex). Conclusions Therefore, AAs have a better glycaemic response to metformin treatment than Whites in the prediabetic population.

      PubDate: 2015-04-14T04:12:24Z
  • Neuregulin 1 affects leptin levels, food intake and weight gain in
           normal-weight, but not obese, db/db mice
    • Abstract: Publication date: April 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 2
      Author(s): G. Ennequin , N. Boisseau , K. Caillaud , V. Chavanelle , M. Etienne , X. Li , C. Montaurier , P. Sirvent
      Aim Studies in vitro have highlighted the potential involvement of neuregulin 1 (NRG1) in the regulation of energy metabolism. This effect has also been suggested in vivo, as intracerebroventricular injection of NRG1 reduces food intakes and weight gain in rodents. Thus, it was hypothesised that NRG1 might affect serum leptin levels in mice. Methods Weight, food intakes, energy expenditure, spontaneous physical activity and serum leptin levels were evaluated in normal-weight C57BL/6JRJ mice following intraperitoneal administration of NRG1 (50μg/kg, three times/week) or saline for 8 weeks. Based on the results of this first experiment, leptin-resistant obese db/db mice were then given NRG1 for 8 weeks. Results Leptin serum concentrations were six times higher in C57BL/6JRJ mice treated with NRG1 than in the animals given saline. NRG1 treatment also reduced weight gain by 10% and food intakes by 15% compared with saline treatment, while energy expenditure remained unchanged. In db/db mice, serum leptin concentrations, weight gain, food intakes, energy expenditure and spontaneous physical activity were not altered by NRG1 treatment. Conclusion The decrease in food intakes and weight gain associated with NRG1 treatment in C57BL/6JRJ mice may be partly explained by increased leptin levels, whereas db/db mice were not affected by the treatment, suggesting resistance to NRG1 in this pathological state.

      PubDate: 2015-04-14T04:12:24Z
  • Impact of socioeconomic status and gender on glycaemic control,
           cardiovascular risk factors and diabetes complications in type 1 and 2
           diabetes: A population based analysis from a Scottish region
    • Abstract: Publication date: April 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 2
      Author(s): A. Collier , S. Ghosh , M. Hair , N. Waugh
      Aims In this cross-sectional study, the aims were to investigate the association of the socioeconomic status and gender on the prevalence of type 1 and 2 diabetes, glycaemic control, cardiovascular risk factors plus the complications of diabetes in a population-based analysis in the county of Ayrshire and Arran, Scotland. Methods Quality Outcome Framework data was obtained from General Practices in Ayrshire and Arran, Scotland (n =15,351 patients). Results In type 1 diabetes, there was an increasing linear trend in HbA1c across deprivation levels (P <0.01). In type 1 diabetes, obesity in women (P <0.01) and increased non-fasting triglyceride levels in both men and women were associated with deprivation (P <0.05). In type 2 diabetes, there was a significant prevalence trend with deprivation for women (P <0.01) but not with glycaemic control (P =0.12). Smoking, ischaemic heart disease and neuropathy (P <0.01) were all associated with increasing deprivation with gender differences. In type 2 diabetes, reduced HDL cholesterol (P <0.01 both genders), and percentage of people on lipid lowering therapy (men P <0.05; women P <0.01) were associated with deprivation. Smoking, ischaemic heart disease, peripheral vascular disease and neuropathy plus foot ulcers (P <0.05) were all associated with increasing deprivation with gender differences. Conclusions Socioeconomic status and gender are associated with changes in glycaemic control and cardiovascular risk factors plus complication development in both type 1 and 2 diabetes. The mechanisms are unclear but follow-up of these patients should allow greater understanding.

      PubDate: 2015-04-14T04:12:24Z
  • Anthropometric markers for detection of the metabolic syndrome in
    • Abstract: Publication date: April 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 2
      Author(s): K. Benmohammed , P. Valensi , M. Benlatreche , M.T. Nguyen , F. Benmohammed , J. Pariès , S. Khensal , C. Benlatreche , A. Lezzar
      Objectives This study aimed to estimate, in a large group of Algerian adolescents, the prevalence of the metabolic syndrome (MetS), using four definitions (by Cook, De Ferranti, Viner and the IDF), and to test the validity of unique thresholds of waist circumference, waist/height ratio and BMI in screening for the MetS regardless of the definition used. Subjects and methods A total of 1100 adolescent students, aged 12–18 y, were randomly selected from schools and classrooms in the city of Constantine; all had anthropometric measurements taken and 989 had blood tests. Results Prevalences of the MetS were: 2.6% for boys and 0.6% for girls by the Cook definition; 4.0% for boys and 2.0% for girls by the De Ferranti definition; 0.7% for boys and 0% for girls by the Viner definition; and 1.3% for boys and 0.5% for girls by the 2007 IDF definition. Prevalences ranged from 3.7% to 13.0% in obese adolescents. Unique thresholds, independent of gender, age and height, of 80cm for waist circumference, 0.50 for waist/height ratio and 25kg/m2 for BMI had sensitivities of 72–100%, 67–100% and 72–100%, respectively, and specificities of 74–78%, 74–86% and 74–78%, respectively, depending on the MetS definition used. Conclusion The MetS is present in Algerian adolescents and the prevalence is especially high in obese young people. Our thresholds for waist circumference, waist/height ratio and BMI for screening for the MetS should now be tested in other adolescent populations.

      PubDate: 2015-04-14T04:12:24Z
  • The dawn phenomenon in type 2 diabetes: How to assess it in clinical
    • Abstract: Publication date: April 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 2
      Author(s): L. Monnier , C. Colette , S. Dejager , D. Owens
      Aim The study was aimed at determining whether the dawn phenomenon in type 2 diabetes (T2D) can be predicted and quantified using simple and easily accessible glucose determinations. Methods A total of 210 non-insulin-treated persons with T2D underwent continuous glucose monitoring (CGM). The dawn phenomenon was quantified as the absolute increment from the nocturnal glucose nadir to the pre-breakfast value (Δdawn, mg/dL). Pre-lunch (preL) and pre-dinner (preD) glucose, and their averaged values (preLD), were compared with the nocturnal nadir. These pre-meal values were subtracted from the pre-breakfast values. The differences obtained (Δpre-mealL, Δpre-meal D and Δpre-meal LD) were correlated with Δdawn values. The receiver operating characteristic (ROC) curve was used to select the optimal Δpre-meal value that best predicted a dawn phenomenon, set at a threshold of 20mg/dL. Results All pre-meal glucose levels and differences from pre-breakfast values (Δpre-meal) significantly correlated (P <0.0001) with the nocturnal nadir and Δdawn values, respectively. The strongest correlations were observed for the parameters averaged at preL and preD time points: r =0.83 for preLD and r =0.58 for Δpre-meal LD. ROC curve analysis indicated that the dawn phenomenon at a threshold of 20mg/dL can be significantly predicted by a Δpre-meal LD cut off value of 10mg/dL. The relationship between Δdawn (Y, mg/dL) and Δpre-meal LD (X, mg/dL) was Y=0.49 X+15. Conclusion The self-monitoring of preprandial glucose values at the three main mealtimes can predict the presence/absence of the dawn phenomenon, and permits reliable assessment of its magnitude without requiring continuous overnight glucose monitoring.

      PubDate: 2015-04-14T04:12:24Z
  • Hypoglycaemia requiring medical assistance in patients with diabetes: A
           prospective multicentre survey in tertiary hospitals
    • Abstract: Publication date: April 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 2
      Author(s): S. Liatis , M. Mylona , S. Kalopita , A. Papazafiropoulou , S. Karamagkiolis , A. Melidonis , A. Xilomenos , I. Ioannidis , G. Kaltsas , L. Lanaras , S. Papas , C. Basagiannis , A. Kokkinos
      Aim Hypoglycaemia is considered a factor contributing to morbidity and mortality in patients with diabetes. The aim of the present study was to examine the frequency, clinical characteristics, predisposing factors and outcomes of iatrogenic hypoglycaemia requiring medical assistance. Methods Eight hospitals participated in this prospective survey of documented iatrogenic hypoglycaemia at their emergency departments. Cases with type 2 diabetes (T2D) were compared with a control group, consisting of patients visiting the outpatients’ diabetes clinics of the same hospitals during the same time period. Results Median survey duration was 16.5 months, and 295 episodes of iatrogenic hypoglycaemia were recorded. Frequency varied across centres from 0.25 to 0.78 cases per 100 presenting patients. Most cases (90.8%) were observed in patients with T2D (mean age: 76.7±10.1 years), while 8.1% of events were recorded in patients with type 1 diabetes (mean age: 42.7±18.3 years). Total in-hospital mortality was 3.4%, and all involved patients with T2D. In T2D patients, advanced age (OR: 1.3 [1.20–1.45] for 5-year increase), use of sulphonylureas (OR: 4.0 [2.5–6.36]), use of insulin (OR: 2.35 [1.42–3.95]), lower estimated GFR (OR: 1.15 [1.07–1.23] at 10mL/min) and number of comorbidities (OR: 1.74 [1.34–2.27]) were each independently associated with hypoglycaemia requiring medical assistance. Conclusion Hypoglycaemia requiring medical assistance in patients with diabetes is a moderately common condition seen in emergency departments and has a mortality rate of 3.4%. The majority of cases involve elderly individuals with T2D who are suffering from serious comorbidities and treated with insulin and/or sulphonylureas.

      PubDate: 2015-04-14T04:12:24Z
  • Frequency and predictors of confirmed hypoglycaemia in type 1 and
           insulin-treated type 2 diabetes mellitus patients in a real-life setting:
           Results from the DIALOG study
    • Abstract: Publication date: April 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 2
      Author(s): B. Cariou , P. Fontaine , E. Eschwege , M. Lièvre , D. Gouet , D. Huet , S. Madani , S. Lavigne , B. Charbonnel
      Aim DIALOG assessed the prevalence and predictors of hypoglycaemia in patients with type 1 (T1DM) or insulin-treated type 2 diabetes mellitus (T2DM) in a real-life setting. Methods In this observational study, insulin-treated patients (n =3048) completed prospective daily questionnaires reporting the frequency and consequences of severe/confirmed non-severe hypoglycaemia over 30 days. Patients (n =3743) also retrospectively reported severe hypoglycaemia over the preceding year. Results In this prospective survey, 85.3% and 43.6% of patients with T1DM and T2DM, respectively, reported experiencing at least one confirmed hypoglycaemic event over 30 days, while 13.4% and 6.4%, respectively, reported at least one severe event. Hypoglycaemia frequency increased with longer duration of diabetes and insulin therapy. Strongly predictive factors for hypoglycaemia were previous hypoglycaemia, >2 injections/day, BMI<30kg/m2 and duration of insulin therapy>10 years. HbA1c level was not predictive of hypoglycaemia in either T1DM or T2DM. The confirmed hypoglycaemia rate was increased in the lowest compared with the highest tertile of HbA1c in T1DM, but not T2DM. At the time of enrolment, physicians reported severe hypoglycaemia in 23.6% and 11.9% of T1DM and T2DM patients, respectively, during the preceding year; the retrospective survey yielded frequencies of 31.5% and 21.7%, respectively. Also, severe hypoglycaemia led to medical complications in 10.7% and 7.8% of events in T1DM and T2DM patients, respectively, over 30 days. Conclusion Using a unique combined prospective and retrospective approach, the DIALOG study found a relatively high frequency of hypoglycaemia among insulin-treated patients. These findings emphasize the importance of a patient-centred approach for managing diabetes in which hypoglycaemia risk evaluation is critical. Trial registration NCT01628341.

      PubDate: 2015-04-14T04:12:24Z
  • Editorial board
    • Abstract: Publication date: April 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 2

      PubDate: 2015-04-14T04:12:24Z
  • Endocrine disruptors: New players in the pathophysiology of type 2
    • Abstract: Publication date: April 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 2
      Author(s): N. Chevalier , P. Fénichel
      The prevalence of type 2 diabetes (T2D) has dramatically increased worldwide during the last few decades. While lifestyle factors, such as decreased physical activity and energy-dense diets, together with genetic predisposition, are well-known actors in the pathophysiology of T2D, there is accumulating evidence suggesting that the increased presence of endocrine-disrupting chemicals (EDCs) in the environment, such as bisphenol A, phthalates and persistent organic pollutants, may also explain an important part in the incidence of metabolic diseases (the metabolic syndrome, obesity and T2D). EDCs are found in everyday products (including plastic bottles, metal cans, toys, cosmetics and pesticides) and used in the manufacture of food. They interfere with the synthesis, secretion, transport, activity and elimination of natural hormones. Such interferences can block or mimic hormone actions and thus induce a wide range of adverse effects (developmental, reproductive, neurological, cardiovascular, metabolic and immune). In this review, both in vivo and in vitro experimental data and epidemiological evidence to support an association between EDC exposure and the induction of insulin resistance and/or disruption of pancreatic β-cell function are summarized, while the epidemiological links with disorders of glucose homoeostasis are also discussed.

      PubDate: 2015-04-14T04:12:24Z
  • Long-term impact of childhood-onset type 1 diabetes on social life,
           quality of life and sexuality
    • Abstract: Publication date: Available online 11 April 2015
      Source:Diabetes & Metabolism
      Author(s): H. Mellerio , S. Guilmin-Crépon , P. Jacquin , M. Labéguerie , C. Lévy-Marchal , C. Alberti
      Aim This study describes the socio-professional outcomes, health-related quality of life (HRQOL) and sexuality of adults with childhood-onset type 1 diabetes (T1D). Methods The study participants (n =388), recruited from a nationwide registry (age: 28.5±3.1 years; T1D duration: 17.0±2.7 years), completed a questionnaire (198 items); the results were compared with the French general population using standardized incidence ratios (SIRs) and Z scores matched for age, gender and period with/without education levels and patterns of family life. Linear regression models also investigated correlates of SF-36 Physical (PCS) and Mental Composite Scores (MCS). Results Compared with the French general population, education levels of people with T1D were similar, with 68.6% having at least a high-school diploma or higher (SIR: 1.06, 95% CI: 0.93; 1.20), as were also their patterns of family life. Unemployment was higher in T1D women (15.3%, SIR: 1.50, 1.00; 2.05), but not in T1D men (8.6%, SIR: 0.96, 0.51; 1.57). Social discrimination was more common (SIR: 5.64, 4.64; 6.62), and frequency of daily alcohol consumption was higher (SIR: men, 3.34, 2.38; 4.54; women, 6.53, 4.57; 12.99). PCS and MCS were decreased moderately (mean±SD: 52.0±7.5; mean Z score: −0.2, 95% CI: −0.3; −0.1) and substantially (mean±SD: 42.1±12.4; mean Z score: −0.7, −0.8; −0.6), respectively. Fatigue and abandoning sports were predictive of a lower HRQOL. Both men and women were more frequently dissatisfied with their sex life. Prevalence of sexual problems was higher in women (SIR for: dysorgasmia, 1.91, 1.21–2.88; decreased/loss of desire: 2.11, 1.35–3.08), but similar in men. Participants with T1D-related complications had preserved social outcomes, but altered HRQOL. Conclusion Young adults with T1D have satisfactory social participation. However, their higher alcohol consumption, lower MCS and frequent dissatisfaction with sexuality suggest a heavy impact of the disease on morale, especially in women. Improving the everyday well-being of these young adults represents a key challenge for diabetes healthcare.

      PubDate: 2015-04-14T04:12:24Z
  • O02 Régulation de la lipolyse et du métabolisme oxydatif
           musculaire par la périlipine 5
    • Abstract: Publication date: March 2015
      Source:Diabetes & Metabolism, Volume 41, Supplement 1
      Author(s): C. Laurens , P.-M. Badin , K. Louche , D.R. Joanisse , D. Langin , V. Bourlier , C. Moro
      Introduction Les triglycérides intramusculares constituent une source d’énergie importante pour le muscle squelettique, notamment au cours d’un exercice physique. Des travaux précédents chez le rongeur indiquent que la périlipine 5 (PLIN5), protéine localisée à la surface de gouttelettes lipidiques de triglycérides, pourrait jouer un rôle dans le métabolisme lipidique musculaire. L’objec-tif de ce travail était de caractériser et d’étudier le rôle de PLIN5 dans la régulation de la lipolyse et du métabolisme oxydatif musculaire. Matériels et méthodes Nous avons caractérisé l’expression protéique de PLIN5 dans différents muscles de souris et chez des individus de poids normal sédentaires, entraînés en endurance, et obèses intolérants au glucose (IGT). Nous avons également surexprimé PLIN5 par une approche adénovirale dans des cultures primaires de cellules musculaires squelettiques humaines pour étudier son rôle fonctionnel dans la régulation du métabolisme énergétique. Résultats Nos résultats montrent que PLIN5 est fortement exprimé dans les muscles oxydatifs par rapport aux muscles glycolytiques. Nous montrons également une forte corrélation positive de PLIN5 avec la sensibilité à l’insuline (r2 = 0,42, p < 0,0001), ainsi qu’une augmentation de son expression chez des individus entraînés et une diminution chez des obèses IGT. Une surexpression de PLIN5 dans des cellules musculaires humaines freine la déplétion en triglycérides (− 53 %, p = 0,0025), ainsi que la mobilisation et l’utilisation des acides gras issus de la lipolyse des triglycérides (− 46 %, p = 0,0035). Ceci s’accompagne d’une augmentation de l’oxydation du glucose et de la synthèse de glycogène, concomitante avec une diminution de l’expression génique de PDK4 (Pyruvate Dehydrogenase Kinase 4). Conclusion Ces résultats indiquent que PLIN5 joue un rôle important dans la régulation de la lipolyse et du métabolisme oxydatif musculaire. PLIN5 pour-rait en partie déterminer la sensibilité à l’insuline en modulant le flux d’acides gras dans le muscle squelettique. Déclaration d’intérêt Les auteurs déclarent ne pas avoir d’intérêt direct ou indirect (financier ou en nature) avec un organisme privé, industriel ou commercial en relation avec le sujet présenté.

      PubDate: 2015-04-05T03:52:16Z
  • Evaluation of the relationship between cardiovascular risk factors and
           periaortic fat thickness in children with type 1 diabetes mellitus
    • Abstract: Publication date: Available online 23 March 2015
      Source:Diabetes & Metabolism
      Author(s): N. Akyürek , M.E. Atabek , B.S. Eklioglu , H. Alp

      PubDate: 2015-04-05T03:52:16Z
  • O01 Obtention d’adipocytes beiges humains fonctionnels in vitro et
           in vivo à partir de cellules souches à pluripotence induite
    • Abstract: Publication date: March 2015
      Source:Diabetes & Metabolism, Volume 41, Supplement 1
      Author(s): A.-C. Guénantin , N. Briand , E. Capel , F. Stillitano , D. Jeziorowska , R. Morichon , J.-P. Siffroi , B. Fève , J. Capeau , J.-S. Hulot , C. Vigouroux
      Rationnel La mise en évidence de tissu adipeux brun puis beige chez l’homme adulte a ouvert de nouvelles perspectives thérapeutiques dans l’obésité et le diabète de type 2. En effet, les adipocytes de ces tissus peuvent, après activation, dissiper l’énergie grâce au découplage mitochondrial médié par UCP1. Les cellules souches humaines à pluripotence induite (hiPSC), issues de la reprogrammation de cellules somatiques, peuvent s’autorenouveler et se différencier dans les trois feuillets embryonnaires, générant une source illimitée de cellules in vitro. Le développement de modèles d’adipocytes beiges en culture à partir de ces cellules constituerait un prérequis permettant d’étudier le développement et la physiologie des adipocytes humains thermogéniques. Matériels et méthodes Nous avons soumis trois lignées d’hiPSC témoins, issues de fibroblastes cutanés, à plusieurs milieux de culture successifs afin d’obtenir des adipocytes beiges sans avoir recours à une surexpression génique ectopique. Résultats Notre méthode de différenciation a permis d’obtenir des précurseurs adipocytaires qui expriment séquentiellement les facteurs adipogéniques C/EBPβ, C/EBPδ, C/EBPα et PPARγ. Après 20 jours de différenciation, les adipocytes expriment la périlipine et Glut-4, stockent des lipides et répondent à l’insuline par une phosphorylation de son récepteur et d’AKT. Leur phénotype beige est attesté par le marquage CITED1, et par l’induction d’UCP1 et de la mitochondriogenèse (induction de PGC1α et DIO2, augmentation du nombre de mitochondries) en réponse aux analogues de l’AMPc. Après injection in vivo chez la souris immunodéficiente, ces précurseurs adipocytaires humains forment un pannicule adipeux. Conclusion Notre méthode originale d’obtention d’adipocytes beiges humains à partir d’hiPSC (demande de brevet FR n º1457357) est simple, rapide et effi-cace. Elle permet d’explorer la physiologie et la physiopathologie de la différenciation adipocytaire beige in vitro. Ces adipocytes pourraient être utilisés pour cribler des molécules thérapeutiques activant la dissipation d’énergie, et ouvrent de nouvelles perspectives en thérapie cellulaire. Déclaration d’intérêt Les auteurs déclarent ne pas avoir d’intérêt direct ou indirect (financier ou en nature) avec un organisme privé, industriel ou commercial en relation avec le sujet présenté.

      PubDate: 2015-04-05T03:52:16Z
  • Predicting factors of hypoglycaemia in elderly type 2 diabetes patients:
           Contributions of the GERODIAB study
    • Abstract: Publication date: Available online 3 April 2015
      Source:Diabetes & Metabolism
      Author(s): L. Bordier , M. Buysschaert , B. Bauduceau , J. Doucet , C. Verny , V. Lassmann Vague , J.P. Le Floch
      The burden of hypoglycaemia is important, particularly in elderly type 2 diabetes (T2D) patients. Unfortunately, however, few studies are available concerning this population. GERODIAB is a prospective, multicentre, observational study that aims to describe the 5-year morbidity and mortality of 987 T2D patients aged 70years and older. After analyzing the frequency of and factors associated with hypoglycaemia in the 6months prior to study inclusion, it was found that hypoglycaemia was associated with retinopathy, lower levels of LDL cholesterol and altered mini-Geriatric Depression Scale (GDS) scores.

      PubDate: 2015-04-05T03:52:16Z
  • Severe hypoglycaemia the “tip of the iceberg”: An
           underestimated risk in both type 1 and type 2 diabetic patients
    • Abstract: Publication date: Available online 29 March 2015
      Source:Diabetes & Metabolism
      Author(s): S. Halimi

      PubDate: 2015-04-05T03:52:16Z
  • Low early B-cell factor 1 (EBF1) activity in human subcutaneous adipose
           tissue is linked to a pernicious metabolic profile
    • Abstract: Publication date: Available online 16 March 2015
      Source:Diabetes & Metabolism
      Author(s): P. Petrus , N. Mejhert , H. Gao , J. Bäckdahl , E. Arner , P. Arner , M. Rydén
      Aim Recently, in both human and murine white adipose tissue (WAT), transcription factor early B-cell factor 1 (EBF1) has been shown to regulate adipocyte differentiation, adipose morphology and triglyceride hydrolysis (lipolysis). This study investigated whether EBF1 expression and biological activity in WAT is related to different metabolic parameters. Methods In this cross-sectional study of abdominal subcutaneous WAT, EBF1 protein levels were examined in 18 non-obese subjects, while biological activity was determined in 56 obese and non-obese subjects. Results were assessed by anthropometric measures and blood pressure as well as by plasma lipid levels and insulin sensitivity. Results EBF1 protein levels were negatively associated with waist circumference (r =−0.56; P =0.015), but not with body mass index (BMI) or body fat (P =0.10–0.29). Biological activity of EBF1 correlated negatively with plasma triglycerides (r =−0.46; P =0.0005) and plasma insulin (r =−0.39; P =0.0027), but positively with plasma HDL cholesterol (r =0.48; P =0.0002) and insulin sensitivity, as assessed by intravenous insulin tolerance test (r =0.64; P <0.0001). These relationships, except for plasma insulin, remained statistically significant after adjusting for BMI and adipose morphology. EBF1 activity was not associated with age, systolic/diastolic blood pressure or total plasma cholesterol (P =0.17–0.48). In contrast to EBF1 activity, after adjusting for BMI, EBF1 mRNA levels displayed only an association with plasma triglycerides. Conclusion Low EBF1 protein expression and activity in abdominal subcutaneous WAT is a BMI-independent marker for several traits associated with the metabolic syndrome. However, whether EBF1 constitutes a novel treatment target remains to be demonstrated.

      PubDate: 2015-03-20T03:19:37Z
  • Antidiabetic agents: Potential anti-inflammatory activity beyond glucose
    • Abstract: Publication date: Available online 18 March 2015
      Source:Diabetes & Metabolism
      Author(s): A.J. Scheen , N. Esser , N. Paquot
      A growing body of evidence is emerging to show that abdominal obesity, the metabolic syndrome, type 2 diabetes, cardiovascular disease and microvascular diabetic complications are intimately related to chronic inflammation. These observations pave the way to the development of new pharmacological strategies that aim to reduce silent inflammation. However, besides specific anti-inflammatory agents, glucose-lowering medications may also exert anti-inflammatory effects that could contribute to improved outcomes in diabetic patients. Most studies have used metformin, an AMP-activated protein kinase (AMPK) activator, and thiazolidinediones (TZDs), which act as peroxisome proliferator-activated receptor-gamma (PPARγ) agonists. Both pharmacological classes (considered insulin-sparing agents or insulin sensitizers) appear to have greater anti-inflammatory activity than insulin-secreting agents such as sulphonylureas or glinides. In particular, TZDs have shown the widest range of evidence of lowered tissue (visceral fat and liver) and serum inflammation. In contrast, despite reducing postprandial hyperglycaemia, the effect of α-glucosidase inhibitors on inflammatory markers appears rather modest, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) and glucagon-like peptide-1 (GLP-1) receptor agonists appear more promising in this respect. These incretin-based therapies exert pleiotropic effects, including reports of anti-inflammatory activity. No human data are available so far regarding sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Although they may have indirect effects due to reduced glucotoxicity, their specific mode of action in the kidneys does not suggest systemic anti-inflammatory activity. Also, in spite of the complex relationship between insulin and atherosclerosis, exogenous insulin may also exert anti-inflammatory effects. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and potential anti-inflammatory effects related to intrinsic actions of the pharmacological class. Finally, it would also be of major clinical interest to define what role the anti-inflammatory effects of these glucose-lowering agents may play in the prevention of macrovascular and microvascular diabetic complications.

      PubDate: 2015-03-20T03:19:37Z
  • Contribution of mitochondria and endoplasmic reticulum dysfunction in
           insulin resistance: Distinct or interrelated roles'
    • Abstract: Publication date: Available online 19 March 2015
      Source:Diabetes & Metabolism
      Author(s): J. Rieusset
      Mitochondria and the endoplasmic reticulum (ER) regulate numerous cellular processes, and are critical contributors to cellular and whole-body homoeostasis. More important, mitochondrial dysfunction and ER stress are both closely associated with hepatic and skeletal muscle insulin resistance, thereby playing crucial roles in altered glucose homoeostasis in type 2 diabetes mellitus (T2DM). The accumulated evidence also suggests a potential interrelationship between alterations in both types of organelles, as mitochondrial dysfunction could participate in activation of the unfolded protein response, whereas ER stress could influence mitochondrial function. The fact that mitochondria and the ER are physically and functionally interconnected via mitochondria-associated membranes (MAMs) supports their interrelated roles in the pathophysiology of T2DM. However, the mechanisms that coordinate the interplay between mitochondrial dysfunction and ER stress, and its relevance to the control of glucose homoeostasis, are still unknown. This review evaluates the involvement of mitochondria and ER independently in the development of peripheral insulin resistance, as well as their potential roles in the disruption of organelle crosstalk at MAM interfaces in the alteration of insulin signalling.

      PubDate: 2015-03-20T03:19:37Z
  • Metabolic roles of PGC-1α and its implications for type 2 diabetes
    • Abstract: Publication date: Available online 5 March 2015
      Source:Diabetes & Metabolism
      Author(s): A. Besseiche , J.-P. Riveline , J.-F. Gautier , B. Bréant , B. Blondeau
      PGC-1α is a transcriptional coactivator expressed in brown adipose tissue, liver, pancreas, kidney, skeletal and cardiac muscles, and the brain. This review presents data illustrating how PGC-1α regulates metabolic adaptations and participates in the aetiology of type 2 diabetes (T2D). Studies in mice have shown that increased PGC-1α expression may be beneficial or deleterious, depending on the tissue: in adipose tissue, it promotes thermogenesis and thus protects against energy overload, such as seen in diabetes and obesity; in muscle, PGC-1α induces a change of phenotype towards oxidative metabolism. In contrast, its role is clearly deleterious in the liver and pancreas, where it induces hepatic glucose production and inhibits insulin secretion, changes that promote diabetes. Previous studies by our group have also demonstrated the role of PGC-1α in the fetal origins of T2D. Overexpression of PGC-1α in β cells during fetal life in mice is sufficient to induce β-cell dysfunction in adults, leading to glucose intolerance. PGC-1α also is associated with glucocorticoid receptors in repressing expression of Pdx1, a key β-cell transcription factor. In conclusion, PGC-1α participates in the onset of diabetes through regulation of major metabolic tissues. Yet, it may not represent a useful target for therapeutic strategies against diabetes as it exerts both beneficial and deleterious actions on glucose homoeostasis, and because PGC-1α modulation is involved in neurodegenerative diseases. However, its role in cellular adaptation shows that greater comprehension of PGC-1α actions is needed.

      PubDate: 2015-03-16T01:41:42Z
  • High-sensitivity C-reactive protein does not improve the differential
           diagnosis of HNF1A–MODY and familial young-onset type 2 diabetes: A
           grey zone analysis
    • Abstract: Publication date: Available online 5 March 2015
      Source:Diabetes & Metabolism
      Author(s): C. Bellanné-Chantelot , J. Coste , C. Ciangura , M. Fonfrède , C. Saint-Martin , C. Bouché , E. Sonnet , R. Valéro , D.-J. Lévy , D. Dubois-Laforgue , J. Timsit
      Aim Low plasma levels of high-sensitivity C-reactive protein (hs-CRP) have been suggested to differentiate hepatocyte nuclear factor 1 alpha–maturity-onset diabetes of the young (HNF1A–MODY) from type 2 diabetes (T2D). Yet, differential diagnosis of HNF1A–MODY and familial young-onset type 2 diabetes (F-YT2D) remains a difficult challenge. Thus, this study assessed the added value of hs-CRP to distinguish between the two conditions. Methods This prospective multicentre study included 143 HNF1A–MODY patients, 310 patients with a clinical history suggestive of HNF1A–MODY, but not confirmed genetically (F-YT2D), and 215 patients with T2D. The ability of models, including clinical characteristics and hs-CRP to predict HNF1A–MODY was analyzed, using the area of the receiver operating characteristic (AUROC) curve, and a grey zone approach was used to evaluate these models in clinical practice. Results Median hs-CRP values were lower in HNF1A–MODY (0.25mg/L) than in F-YT2D (1.14mg/L) and T2D (1.70mg/L) patients. Clinical parameters were sufficient to differentiate HNF1A–MODY from classical T2D (AUROC: 0.99). AUROC analyses to distinguish HNF1A–MODY from F-YT2D were 0.82 for clinical features and 0.87 after including hs-CRP. For the grey zone analysis, the lower boundary was set to miss<1.5% of true positives in non-tested subjects, while the upper boundary was set to perform 50% of genetic tests in individuals with no HNF1A mutation. On comparing HNF1A–MODY with F-YT2D, 65% of patients were classified in between these categories – in the zone of diagnostic uncertainty – even after adding hs-CRP to clinical parameters. Conclusion hs-CRP does not improve the differential diagnosis of HNF1A–MODY and F-YT2D.

      PubDate: 2015-03-16T01:41:42Z
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