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Journal Cover   Diabetes & Metabolism
  [SJR: 0.871]   [H-I: 56]   [47 followers]  Follow
    
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   ISSN (Print) 1262-3636
   Published by Elsevier Homepage  [2589 journals]
  • EDB
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6




      PubDate: 2015-02-06T08:29:02Z
       
  • Regulation of growth hormone induced JAK2 and mTOR signalling by hepatic
           protein tyrosine phosphatase 1B
    • Abstract: Publication date: February 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 1
      Author(s): C. Owen , E.K. Lees , N. Mody , M. Delibegović
      Protein tyrosine phosphatase 1B (PTP1B) regulates various signalling pathways including insulin, leptin, IGF-1 and growth hormone (GH) signalling. Transmission of the GH signal depends on Janus kinase 2 (JAK2), which is how PTP1B is thought to modulate GH signalling in the liver, based on studies utilising global PTP1B knockout mice (Ptp1b −/−). Here, we investigated the liver-specific role of PTP1B in GH signalling, using liver-specific Ptp1b −/− mice (alb-crePtp1b −/−), under physiological (chow) or insulin resistant (high-fat diet [HFD]) feeding conditions. Body weight and adiposity were comparable between female alb-crePtp1b −/− and Ptp1b fl/fl control mice. On chow diet, under 48-hour fasting GH-resistant conditions, GH stimulation in vivo led to a robust stimulation of the JAK-STAT signalling pathway. Alb-crePtp1b −/− mice exhibited significantly higher GH-induced JAK2 phosphorylation and SOCS3 gene expression post-GH stimulation. However, STAT3, STAT5 and ERK1/2 phosphorylation and SOCS2 gene expression were similar between groups. Interestingly, GH-induced mTOR phosphorylation was significantly higher in alb-crePtp1b −/− mice 5-min post-GH stimulation compared to controls, revealing this part of the pathway under direct control of PTP1B. Under ad lib HFD-fed conditions, GH-induced STAT5 phosphorylation significantly increased in alb-crePtp1b −/− mice only, with no alterations in the controls. Overall, our data demonstrate that liver-specific PTP1B deletion leads to significant alterations in GH signalling with increased JAK2, STAT5 and mTOR phosphorylation and SOCS3 gene expression.


      PubDate: 2015-02-06T08:29:02Z
       
  • Associations between the common HNF1A gene variant p.I27L (rs1169288) and
           risk of type 2 diabetes mellitus are influenced by weight
    • Abstract: Publication date: February 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 1
      Author(s): K. Morita , J. Saruwatari , T. Tanaka , K. Oniki , A. Kajiwara , K. Otake , Y. Ogata , K. Nakagawa
      Aim The common variants p.I27L (rs1169288), p.A98V (rs1800574) and p.S487N (rs2464196) of the hepatocyte nuclear factor 1-α (HNF1A) gene have been inconsistently associated with impaired glucose tolerance and/or an increased risk of type 2 diabetes mellitus (T2DM). The present study aimed to investigate whether these associations are affected by weight. Methods A cross-sectional analysis was conducted among 861 Japanese subjects (males: 65.5%; 61.8±12.3years) attending a health-screening programme. Interactive effects between HNF1A variants and weight status on risk of T2DM or dysglycaemic status were determined. Results The 27L variant carriers were at higher risk of T2DM and dysglycaemic status than non-carriers, but only in normal-weight subjects [odds ratio (OR): 2.04, P =0.03 and OR: 2.56, P =0.01, respectively]. An interactive effect of the p.I27L (rs1169288) variant and weight status on the risk of dysglycaemic status was found (P =0.04). Age, but not body mass index (BMI), was a risk factor for dysglycaemic status in the 27L carriers (OR: 1.05, P =0.0003), whereas BMI was a risk factor in non-carriers (OR: 1.23, P =0.008). No carriers of 98V were identified, and 487N was not associated with either T2DM or dysglycaemic status in our study population. Conclusion These findings suggest that the HNF1A p.I27L (rs1169288) variant may be a significant risk factor of T2DM in normal-weight subjects and that earlier inconsistent results may have been due, in part, to subjects’ weight status. Further investigations in larger cohorts are needed to verify these findings.


      PubDate: 2015-02-06T08:29:02Z
       
  • Comparison of PEGylated FGF-21 with insulin glargine for long-lasting
           hypoglycaemic effect in db/db mice
    • Abstract: Publication date: February 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 1
      Author(s): X. Ye , J. Qi , Y. Wu , D. Yu , P. Xu , S. Li , S. Zhu , Q. Wu , G. Ren , D. Li
      Aim This study investigated the long-acting antidiabetic efficacy of PEGylated fibroblast growth factor (FGF)-21 in type 2 diabetic db/db mice. Methods PEGylated FGF-21 was prepared by modifying the N-terminus of human FGF-21 (hFGF-21) using mPEG-ALD. To compare the long-lasting hypoglycaemic effects of PEGylated FGF-21 and insulin glargine in diabetic db/db mice, their pharmacological efficacy was evaluated by changes in blood glucose levels, body weight, insulin levels, glycosylated haemoglobin levels, lipid profile and liver function parameters, and by oral glucose tolerance tests (OGTTs). Results Both PEGylated FGF-21 and insulin glargine decreased plasma glucose in db/db mice. However, compared with insulin glargine treatment, PEGylated FGF-21 therapy had more significant effects in lowering blood glucose and glycosylated haemoglobin levels, improving lipid profile and liver function parameters, alleviating insulin resistance and reducing the glucose area under the curve in OGTTs. Conclusion Our results suggest that PEGylated FGF-21 is an ideal candidate as a long-acting antidiabetes drug, and holds significant promise as an effective therapeutic agent in the treatment of type 2 diabetes patients.


      PubDate: 2015-02-06T08:29:02Z
       
  • Prevalence of anxiety and depression among diabetic African patients in
           Guinea: Association with HbA1c levels
    • Abstract: Publication date: February 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 1
      Author(s): A. Camara , N.M. Baldé , S. Enoru , J.S. Bangoura , E. Sobngwi , F. Bonnet
      Aim The prevalence and risk factors associated with symptoms of anxiety and depression were determined in African people with diabetes. Methods This cross-sectional study involved 491 outpatients with type 2 diabetes (T2D) recruited from four diabetes clinics (Conakry, Labé, Boké and Kankan) in Guinea. The Hospital Anxiety and Depression Scale (HADS) was used to evaluate symptoms of anxiety and depression. Logistic regression analysis stratified by gender was performed to identify the associated risk factors. Results Anxiety and depression symptoms were present in 58.7% and 34.4%, respectively, of the 491 patients with T2D (62.7% women, mean±SD age: 57.9±10.2years). Odds ratios (95% CI) of risk factors independently associated with anxiety were urban residence [2.98 (1.81–4.89)] in women, and low socioeconomic status [0.19 (0.05–0.70)] and HbA1c ≥9.0% [2.61 (1.0–6.39)] in men. Factors associated with depression were urban residence [2.13 (1.27–3.58)], older age [1.03 (1.01–1.06)], low socioeconomic status [2.21 (1.34–3.66)] and no previous measurement of HbA1c [12.45 (1.54–100.34)] in women, and insulin therapy [2.28 (1.05–4.92)] and HbA1c ≥9.0% [3.85 (1.02–14.48)] in men. Conclusion Anxiety and depression symptoms in people with type T2D are common in Guinea. Urban residence, low socioeconomic status and high levels of HbA1c were significantly associated with a greater risk of anxiety and depression, highlighting the psychological burden related to diabetes in Africa.


      PubDate: 2015-02-06T08:29:02Z
       
  • A family history of diabetes determines poorer glycaemic control and
           younger age of diabetes onset in immigrants from the Middle East compared
           with native Swedes
    • Abstract: Publication date: February 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 1
      Author(s): L. Bennet , U. Lindblad , P.W. Franks
      Aims Immigrant populations from the Middle East develop diabetes earlier than indigenous European populations; however, the underlying etiology is poorly understood. This study looked at the risk factors associated with early diabetes onset and, in non-diabetics, glycaemic control in immigrants from Iraq compared with native Swedes. Methods This cross-sectional population-based study comprised 1398 Iraqi immigrants and 757 Swedes (ages 30–75years) residing in the same area of Malmö, Sweden. Outcomes were age at diabetes onset and glycaemic control (HbA1c) as assessed by Cox proportional hazards and linear regression, respectively. Results In Iraqis vs Swedes, clustering in the family history (in two or more relatives) was more prevalent (23.2% vs 3.6%, P <0.001) and diabetes onset occurred earlier (47.6years vs 53.4years, P =0.001). Having an Iraqi background independently raised the hazard ratio (HR) for diabetes onset. Diabetes risk due to family history was augmented by obesity, with the highest HRs observed in obese participants with clustering in the family history (HR: 5.1, 95% CI: 3.2–8.2) after adjusting for country of birth and gender. In participants without previously diagnosed diabetes (Iraqis: n =1270; Swedes: n =728), HbA1c levels were slightly higher in Iraqis than in Swedes (4.5% vs 4.4%, P =0.038). This difference was explained primarily by clustering in the family history rather than age, obesity, lifestyle or socioeconomic status. Conclusion The study shows that the greater predisposition to diabetes in Middle Eastern immigrants may be explained by a more extensive family history of the disorder; clinical interventions tailored to Middle Eastern immigrants with such a family history are thus warranted.


      PubDate: 2015-02-06T08:29:02Z
       
  • Physical activity at home, at leisure, during transportation and at work
           
    • Abstract: Publication date: February 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 1
      Author(s): L. Cloix , A. Caille , C. Helmer , I. Bourdel-Marchasson , A. Fagot-Campagna , C. Fournier , P. Lecomte , J.M. Oppert , D. Jacobi
      Aim Our study assessed the distribution of physical activity during various typical tasks of daily life in adults with type 2 diabetes (T2D), a population typified by low physical activity. Methods We investigated the duration and intensity of physical activity in four domains (work, leisure, transportation and domestic), and how individual determinants might influence the repartition. The long-form International Physical Activity Questionnaire (IPAQ) was administered to participants from the échantillon national témoin représentatif des personnes diabétiques (ENTRED), a study of French adults with T2D (n =724, 65% men, age 62±10y, BMI 29±5kg.m−2, HbA1c 7.1±1.1%), and the associations between sociodemographic/clinical characteristics and categories of physical activity intensity (low, moderate or high) were examined by logistic regression. Results The median total physical activity was 2079 [Q1=893, Q3=3915]MET-min·week−1. The main contributors to total physical activity were domestic chores, followed by leisure-time activities and transportation (median: 630, 347 and 198MET-min·week−1, respectively). Absence of cardiovascular complications (OR=1.87, 95% CI=1.01–3.47), age<65y (OR=2.28, 95% CI=1.30–4.01) and better self-perceived health (OR=2.12, 95% CI=1.18–3.83) were associated with more physical activity. In all patient subgroups (defined by category of physical activity intensity or stratified by determinants of physical activity level), domestic chores were always the main contributor to total physical activity (P <0.0001). Conclusion Domestic chores are the predominant routine whereby adults with T2D engage in physical activity. This emphasizes the vast potential for promoting voluntary leisure-time physical activity in this population.


      PubDate: 2015-02-06T08:29:02Z
       
  • Editorial board
    • Abstract: Publication date: February 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 1




      PubDate: 2015-02-06T08:29:02Z
       
  • Anaemia, a common but often unrecognized risk in diabetic patients: A
           review
    • Abstract: Publication date: February 2015
      Source:Diabetes & Metabolism, Volume 41, Issue 1
      Author(s): A. Angelousi , E. Larger
      Anaemia in patients with diabetes, both type 1 and type 2, is a frequent clinical finding. The mechanisms of anaemia are multifactorial and often not very well understood. Iatrogenic causes, including oral antidiabetic drugs, ACE inhibitors and ARBs, and renal insufficiency are the major causes of anaemia in patients with type 2 diabetes. In patients with type 1, the cause is often an associated autoimmune disease, and screening for autoimmune gastritis, pernicious anaemia, Hashimoto's thyroiditis, coeliac disease and Addison's disease is recommended. Other rare causes – including G6PD deficiency, microangiopathic haemolytic anaemia and thiamine-responsive megaloblastic anaemia – should be suspected in young patients or when the classical causes are excluded. Early detection and recognition of the cause(s) of anaemia in patients with diabetes could help to prevent other clinical manifestations as well as the complications of diabetes.


      PubDate: 2015-02-06T08:29:02Z
       
  • Impact of diabetes on neutrophil-to-lymphocyte ratio and its relationship
           to coronary artery disease
    • Abstract: Publication date: Available online 2 February 2015
      Source:Diabetes & Metabolism
      Author(s): M. Verdoia , A. Schaffer , L. Barbieri , G. Aimaretti , P. Marino , F. Sinigaglia , H. Suryapranata , G. De Luca
      Background Coronary artery disease (CAD) is the leading cause of mortality among diabetic patients, and the neutrophil-to-lymphocyte ratio (NLR) has recently emerged from among inflammatory parameters as a potential indicator of vascular complications and poorer outcome in patients with diabetes. This study aimed to evaluate: 1) the impact of diabetes on NLR; and 2) the role of NLR on the extent of CAD among diabetic patients undergoing coronary angiography. Methods Consecutive patients undergoing coronary angiography were included. Diabetic status and main chemistry parameters were assessed at the time of admission. Significant CAD was defined as at least one vessel with stenosis>50%, while severe CAD was left main and/or three-vessel disease, as evaluated by quantitative coronary angiography (QCA). Results Diabetes was observed in 1377 of 3756 patients (36.7%); they were older, and displayed higher-risk cardiovascular profile and more complex CAD. Diabetic status was also associated with a significant increase in NLR (P =0.004). Among diabetics, higher NLR tertile values were related to ageing (P <0.001), dyslipidaemia (P <0.001), renal failure (P <0.001), body mass index (P <0.001), previous percutaneous coronary revascularization (P =0.004) and cerebrovascular events (P =0.003), acute presentation (P <0.001), treatment at admission with beta-blockers/statins/ASA (all P <0.001), diuretics (P =0.01) or clopidogrel (P =0.04), platelet count (P =0.03), white blood cell count, creatinine, glycaemia and C-reactive protein (P <0.001), and inversely related to haemoglobin, triglyceride levels (P <0.001) and smoking (P =0.03). NLR was associated with multivessel disease (P <0.001), degree of stenosis (P =0.01), type C lesions (P =0.02), coronary calcifications and intracoronary thrombus (P <0.001), but inversely with in-stent restenosis (P =0.003) and TIMI flow grade (P =0.02). Also, NLR was directly related to CAD prevalence (P <0.001; adjusted OR [95% CI]: 1.62 [1.27–2.07], P <0.001) and CAD severity (P <0.001; adjusted OR [95% CI]: 1.19 [1.00–1.43], P =0.05). Conclusion NLR is increased among diabetic patients and, in such patients, is independently associated with the prevalence and severity of CAD. Further studies are now needed to confirm present results and to evaluate the underlying pathophysiological mechanisms behind our findings.


      PubDate: 2015-02-05T08:23:39Z
       
  • Intermittent hypoxia is an independent marker of poorer glycaemic control
           in patients with uncontrolled type 2 diabetes
    • Abstract: Publication date: Available online 3 February 2015
      Source:Diabetes & Metabolism
      Author(s): M. Torrella , I. Castells , G. Gimenez-Perez , A. Recasens , M. Miquel , O. Simó , E. Barbeta , G. Sampol
      Aim This study investigated the association between intermittent hypoxia and glycaemic control in patients with uncontrolled type 2 diabetes (T2D) not treated for sleep apnoea. Methods This was a single-centre cross-sectional study of stable patients with T2D and HbA1c ≥7% (53mmol/mol). Patients underwent overnight pulse oximetry and, if intermittent hypoxia—defined by a 4% oxyhaemoglobin desaturation index≥15—was observed, respiratory polygraphy was performed. All participants completed the Pittsburgh Sleep Questionnaire and Hospital Anxiety and Depression Scale. The association between intermittent hypoxia and poorer glycaemic control (defined by an HbA1c level above the median of 8.5%) was estimated by multivariate logistic regression analysis. Results Out of 145 patients studied, 54 (37.2%) had intermittent hypoxia (with sleep apnoea confirmed in 53). Patients with intermittent hypoxia had 0.7% (7.7mmol/mol) higher median HbA1c levels than patients without intermittent hypoxia (P =0.001). Intermittent hypoxia was associated with poorer glycaemic control after adjusting for obesity, age at onset and duration of diabetes, insulin requirement, sleep quality and depressive mood (OR: 2.31, 95% CI: 1.06–5.04, model adjusted for body mass index; OR: 2.46, 95% CI: 1.13–5.34, model adjusted for waist-to-height ratio). Conclusion Intermittent hypoxia, a consequence of sleep apnoea, is frequent and has a strong independent association with poorer glycaemic control in patients with uncontrolled T2D.


      PubDate: 2015-02-05T08:23:39Z
       
  • More effective glycaemic control by metformin in African Americans than in
           Whites in the prediabetic population
    • Abstract: Publication date: Available online 4 February 2015
      Source:Diabetes & Metabolism
      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: 2015-02-05T08:23:39Z
       
  • Outcome of twin pregnancies associated with glucose intolerance
    • Abstract: Publication date: Available online 27 January 2015
      Source:Diabetes & Metabolism
      Author(s): C. Poulain , A. Duhamel , C. Garabedian , M. Cazaubiel , M.C. Rejou , A. Vambergue , P. Deruelle
      Objectives There is little information about the impact of hyperglycaemia in twin pregnancies. The objective of our study was to evaluate the maternal, foetal and neonatal complications in patients with twin pregnancy and glucose intolerance defined by gestational diabetes mellitus and gestational mild hyperglycaemia. Study design We performed a single-centre retrospective study. Screening for gestational diabetes was achieved by a two-step method. Patients were managed according to the French guidelines. After matching for age and body mass index, outcomes were compared in 177 patients with glucose intolerance and 509 controls. Macrosomia was defined as birth weight above the 90th percentile of gestational age adjusted for parity, foetal sex and maternal biometrics. Results Prevalence of glucose intolerance was 17.5% in our population. Complications of pregnancy and mode of delivery were similar between the two groups. Caesarean section was associated with age>35years, vascular complications of pregnancy and non-cephalic presentation of the first twin. Rate of macrosomia was not different between the two groups. The only risk factor for macrosomia was a history of macrosomia in a previous pregnancy (odds ratio=5.9, 95% confidence interval=1.8–19.2). Conclusion Twin pregnancies complicated by glucose intolerance were not associated with an increased risk of macrosomia or Caesarean section. Further studies should assess the value of screening gestational diabetes mellitus in twin pregnancies.


      PubDate: 2015-01-30T07:50:07Z
       
  • Sleep habits and diabetes
    • Abstract: Publication date: Available online 23 January 2015
      Source:Diabetes & Metabolism
      Author(s): S. Larcher , P.-Y. Benhamou , J.-L. Pépin , A.-L. Borel
      Sleep duration has been constantly decreasing over the past 50years. Short sleep duration, sleep quality and, recently, long sleep duration have all been linked to poor health outcomes, increasing the risk of developing metabolic diseases and cardiovascular events. Beyond the duration of sleep, the timing of sleep may also have consequences. Having a tendency to go early to bed (early chronotype) compared with the habit of going to bed later (late chronotype) can interfere considerably with social schedules (school, work). Eventually, a misalignment arises in sleep timing between work days and free days that has been described as ‘social jet lag’. The present review looks at how different sleep habits can interfere with diabetes, excluding sleep breathing disorders, and successively looks at the effects of sleep duration, chronotype and social jet lag on the risk of developing diabetes as well as on the metabolic control of both type 1 and type 2 diabetes. Finally, this review addresses the current state of knowledge of physiological mechanisms that could be linking sleep habits and metabolic health.


      PubDate: 2015-01-26T07:13:00Z
       
  • Neuregulin 1 affects leptin levels, food intake and weight gain in
           normal-weight, but not obese, db/db mice
    • Abstract: Publication date: Available online 5 January 2015
      Source:Diabetes & Metabolism
      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: 2015-01-08T05:57:26Z
       
  • Anthropometrics indices of obesity, and all-cause and cardiovascular
           disease-related mortality, in an Asian cohort with type 2 diabetes
           mellitus
    • Abstract: Publication date: Available online 6 January 2015
      Source:Diabetes & Metabolism
      Author(s): R.B.T. Lim , C. Chen , N. Naidoo , G. Gay , W.E. Tang , D. Seah , R. Chen , N.C. Tan , J. Lee , E.S. Tai , K.S. Chia , W.Y. Lim
      Aim The study investigated the relationship of general (body mass index [BMI]) and central (waist circumference [WC]; waist–hip ratio [WHipR]; waist–height ratio [WHeightR]) adiposity with all-cause and cardiovascular disease (CVD)-related mortality in an Asian population with diabetes. Methods A total of 13,278 participants with type 2 diabetes mellitus (T2DM) recruited from public-sector primary-care and specialist outpatients clinics in Singapore were followed-up for a median duration of 2.9 years, during which time there were 524 deaths. Cox proportional-hazards regression and competing-risk models were used to obtain hazard ratios (HRs) for anthropometric variables of all-cause and CVD-related mortality. Results After adjusting for BMI, the highest quintiles of WC, WHipR and WHeightR were all positively associated with mortality compared with the lowest quintiles, with WHeightR exhibiting the largest effect sizes [all-cause mortality HR: 2.13, 95% confidence interval (CI): 1.33–3.42; CVD-related mortality HR: 3.42, 95% CI: 1.62–7.19]. Being overweight but not obese (BMI:≥23.0 but<27.5kg/m2) was associated with a decreased risk of CVD-related mortality in those aged≥65 years (HR: 0.47, 95% CI: 0.29–0.75), but not in those aged<65 years (HR: 1.11, 95% CI: 0.49–2.50). Conclusion Overweight, but not obesity, was associated with a reduction in risk of mortality. This was seen in T2DM patients aged≥65 years, but not in those younger than this. At the same BMI, having higher central-obesity indices such as WC, WHipR and WHeightR also increased the risk of mortality.


      PubDate: 2015-01-08T05:57:26Z
       
  • Editorial. SGLT-2 receptor inhibitors: An opportunity to revise our
           therapeutic strategy for type 2 diabetes'
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6, Supplement 1
      Author(s): Fabrice Bonnet , André J. Scheen



      PubDate: 2015-01-03T05:05:30Z
       
  • Adverse effects and safety of SGLT-2 inhibitors
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6, Supplement 1
      Author(s): S. Halimi , B. Vergès
      In type 2 diabetes (T2DM), glycaemic control delays the development and slows the progression of complications. Although there are numerous glucose-lowering agents in clinical use, only approximately half of T2DM patients achieve glycaemic control, while undesirable side-effects, such as hypoglycaemia and body weight gain, often impede treatment in those taking these medications. Thus, there is a need for novel agents and treatment options. Sodium – glucose cotransporter-2 inhibitors (SGLT-2-i) have recently been developed for the treatment of T2DM. The available data suggest a good tolerability profile for the three available drugs – canagliflozin, dapagliflozin and empagliflozin – approved by the US Food and Drug Administration (FDA) for the American market as well as in other countries. The most frequently reported adverse events with SGLT-2-i are female genital mycotic infections, urinary tract infections and increased urination. The pharmacodynamic response to SGLT-2-i declines with increasing severity of renal impairment, requiring dosage adjustments or restrictions with moderate-to-severe renal dysfunction. Most patients treated with SGLT-2-i also have a modest reduction in blood pressure and modest effects on serum lipid profiles, some of which are beneficial (increased high-density lipoprotein cholesterol and decreased triglycerides) and others which are not (increased low-density lipoprotein cholesterol, LDL-C). A number of large-scale and longer-term cardiovascular trials are now ongoing. In patients treated with dapagliflozin, a non-significant excess number of breast and bladder cancers has been reported; considered as due to a bias, this is nevertheless being followed in the ongoing trials. No other significant safety issues have been reported so far. Although there is some benefit for several cardiovascular risk factors such as HbA1c, high blood pressure, obesity and increases in LDL-C, adequately powered trials are still required to determine the effects of SGLT-2-i on macrovascular outcomes.


      PubDate: 2015-01-03T05:05:30Z
       
  • SGLT-2 inhibition in patients with kidney disease
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6, Supplement 1
      Author(s): R.E. Gilbert
      Accustomed to managing diabetes with agents that mostly act by modulating the secretion and actions of insulin, with the advent of sodium-glucose linked transporter-2 (SGLT-2) inhibitors, physicians are now aware that the kidney also needs to be considered in the spectrum of action of anti-hyperglycaemic agents. Though familiar with the need for dose adjustment when prescribing many of our current anti-hyperglycaemic drugs in the setting of kidney dysfunction, with the SGLT-2 inhibitors pharmacodynamic as well as pharmacokinetic aspects also need to be considered. Finally, through their ability to reduce intraglomerular pressure, systemic blood pressure and plasma uric acid concentration, the SGLT-2 inhibitors offers the possibility of kidney protection. An hypothesis that will need to be tested with long term studies that address changes in the kidney beyond albuminuria, assessing the rate of decline in glomerular filtration rate and ‘hard’kidneyrelated endpoints such as the need for renal replacement therapy (dialysis, transplantation) will be important in this setting.


      PubDate: 2015-01-03T05:05:30Z
       
  • Beyond Glycosuria: Exploring the intrarenal effects of SGLT-2 inhibition
           in diabetes
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6, Supplement 1
      Author(s): M.C. Thomas , K. Jandeleit-Dahm , F. Bonnet
      For millennia, the syndrome that has become known as diabetes was considered to be primarily a disease of the urinary system and, by association, of dysfunction in the kidneys (recognized as the source of urine). In the last decade, there has been renewed interest in the role of the kidneys in the development and maintenance of high glucose levels. This has led to the development of novel agents to inhibit sodiumglucose cotransporter 2 (SGLT-2) as a means to control glucose levels and augment calorie-wasting leading to weight loss. However, beyond actions on glycaemic control, inhibition of proximal glucose absorption via SGLT-2 has significant direct effects to attenuate hyperfiltration and reduce renal hypertrophy. Increased distal sodium delivery may also act to suppress the intrarenal renin-angiotensin-aldosterone system, although systemic activity may be modestly increased due to osmotic diuresis. Reducing proximal glucose reabsorption may also protect the tubular cells from exposure to excess glucose and glucose-induced reactive oxygen species. On the other hand, distal glucose delivery following inhibition of SGLT-2 may increase glycogen deposition, the significance of which is unclear. However, subjects with familial glycosuria appear to have a benign renal prognosis. Some studies have demonstrated significant reductions in albumin excretion in various experimental models and as post-hoc observations in clinical trials. Whether these reflect renoprotection or are simply the result of intraglomerular haemodynamic changes remains unclear. Although promising, such actions remain to be established by comprehensive clinical trials with a renal focus, many of which are currently in progress.


      PubDate: 2015-01-03T05:05:30Z
       
  • Familial renal glycosuria and modifications of glucose renal excretion
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6, Supplement 1
      Author(s): D. Prié
      Under physiological conditions, the kidneys contribute to glucose homoeostasis by producing glucose by gluconeogenesis and preventing glucose loss in urine. The glucose filtered by the glomeruli is completely reabsorbed in the renal proximal tubule. Renal gluconeogenesis produces 25% of the circulating glucose in the postabsorptive state, while the amount of glucose reabsorbed by the kidneys largely exceeds the quantity synthesized by kidney gluconeogenesis. Sodium-glucose cotransporter type 2 (SGLT-2) and glucose transporter 2 (GLUT2) carry out more than 90% of renal glucose uptake. In diabetes, both gluconeogenesis and renal glucose reabsorption are increased. The augmentation of glucose uptake in diabetes is due to the overexpression of renal glucose transporters SGLT-2 and GLUT2 in response to the increase in expression of transcription activator hepatic nuclear factor 1-alpha (HNF1α). The rise in glucose uptake contributes to hyperglycaemia and induces glomerular hyperfiltration by increasing sodium and water reabsorption in the proximal tubule that, in turn, modifies urine flux at the macula densa. SGLT-2 inhibitors improve glycaemic control and prevent renal hyperfiltration in diabetes. Loss of SGLT-2 transporter function is a benign state characterized by glycosuria. In contrast, mutations of other glucose transporters expressed in the kidney are responsible for severe disorders.


      PubDate: 2015-01-03T05:05:30Z
       
  • Metabolic effects of SGLT-2 inhibitors beyond increased glucosuria: A
           review of the clinical evidence
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6, Supplement 1
      Author(s): A.J. Scheen , N. Paquot
      Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by facilitating glucose excretion through the kidneys. However, this simple renal mechanism that results in sustained glucose urinary loss leads to more complex indirect metabolic effects. First, by reduction of chronic hyperglycaemia and attenuation of glucose toxicity, SGLT-2 inhibitors can improve both insulin secretion by beta cells and peripheraltissue insulin sensitivity. In the case of canagliflozin, because of low-potency SGLT1 inhibition, a non-renal (intestinal) effect may also be considered, which may contribute to better control of postprandial hyperglycaemia, although this contribution remains to be better analyzed in humans. Second, chronic glucose loss most probably leads to compensatory mechanisms. One of them, although not well evidenced in humans, might involve an increase in energy intake, an effect that may limit weight loss in the long run. Another could be an increase in endogenous glucose production, most probably driven by increased glucagon secretion, which may somewhat attenuate the glucoselowering effect. Nevertheless, despite these compensatory mechanisms and most probably because of the positive effects of the reduction in glucotoxicity, SGLT-2 inhibitors exert clinically relevant glucose-lowering activity while promoting weight loss, a unique dual effect among oral antidiabetic agents. Furthermore, the combination of SGLT-2 inhibitors with other drugs that either have anorectic effects (such as incretin-based therapies) or reduce hepatic glucose output (like metformin) and, thus, may dampen these two compensatory mechanisms appears appealing for the management of type 2 diabetes mellitus.


      PubDate: 2015-01-03T05:05:30Z
       
  • Relationship between cardiac tissue glycation and skin autofluorescence in
           patients with coronary artery disease
    • Abstract: Publication date: Available online 29 December 2014
      Source:Diabetes & Metabolism
      Author(s): B. Hofmann , K. Jacobs , A. Navarrete Santos , A. Wienke , R.E. Silber , A. Simm
      Aim During ageing, advanced glycation end-products (AGEs) accumulate in extracellular matrix proteins like collagen and contribute to a decline in organ function. As skin autofluorescence (sAF) can assess subcutaneous accumulation of fluorescent AGEs, this study aimed to investigate the relationship between AGE-modified cardiac tissue collagen and AGE-related sAF in coronary artery bypass graft (CABG) surgery patients. Methods Between January 2011 and January 2012, data from 72 consecutive male patients undergoing isolated CABG were prospectively recorded. Collagen fractions were isolated from the right atrial appendages of these patients by proteolysis and collagenase digestion. Collagen was quantified by hydroxyproline assay, and AGEs by AGE-related intrinsic fluorescence; sAF was measured using an autofluorescence reader. Results Biochemical analysis showed that the insoluble cardiac collagen fraction contained the highest amounts of accumulated AGEs; the AGE-related intrinsic fluorescence of this fraction increased with age (P =0.0001), blood glucose (P =0.002), HbA1c (P =0.01) and sAF (P =0.008). Conclusion This study demonstrated for the first time a relationship between cardiac tissue glycation and AGE-related sAF. In addition, cardiac tissue glycation was associated with age, blood glucose and long-term glucose values in patients with coronary artery disease.


      PubDate: 2015-01-03T05:05:30Z
       
  • Adverse drug reaction: A possible case of glimepiride-induced syndrome of
           inappropriate antidiuretic hormone secretion
    • Abstract: Publication date: Available online 2 January 2015
      Source:Diabetes & Metabolism
      Author(s): H. Adachi , H. Yanai



      PubDate: 2015-01-03T05:05:30Z
       
  • Type 2 diabetes mellitus in France in 2012: Results from the ObEpi survey
    • Abstract: Publication date: Available online 24 December 2014
      Source:Diabetes & Metabolism
      Author(s): E. Eschwege , A. Basdevant , A. Crine , C. Moisan , M.-A. Charles
      Aim This analysis estimates the prevalence of type 2 diabetes mellitus (T2DM) in French adults participating in the ObEpi (obesity epidemiology) 2012 survey and also proposes a description of that population, according to comorbidities, treatments and sociodemographic factors related to the disease. Methods A self-administered questionnaire was posted to 20,000 households from the Kantar Health panel. In total, 25,714 adults aged≥18 years and representative of the French population completed the survey between January and March 2012. Results The prevalence of T2DM was 5.5±0.3% (95% CI) in this representative sample of the adult French population. Average age of patients was 65.9 years; 55% were men. Mean body mass index was 29.9kg/m2 (men: 29.4kg/m2, women: 30.6 kg/m2; P< 0.01); the prevalence of obesity was 43.1% (men: 39.9%, women: 47.1%; P< 0.01). Patient-reported treatments for comorbidities were frequent: high blood pressure, 59.1%; dyslipidaemia, 59.9%; myocardial infarction/angina pectoris, 9.7%; revascularization, 7.8%; heart failure, 7.4%; sleep apnoea, 8.3%; and osteoarthritis, 10.7%. With regards to known treatments, 81.4% of patients were taking oral antidiabetic drugs (OADs), and 15.3% were using insulin therapy. Also, 18.8% of diabetic respondents reported financial hardship. Conclusion T2DM remains a disease of major concern: compared with the non-diabetic population, all parameters surveyed showed unfavourable ratings, particularly for women.


      PubDate: 2014-12-29T04:57:59Z
       
  • Increased TSH in obesity: Evidence for a BMI-independent association with
           leptin
    • Abstract: Publication date: Available online 22 December 2014
      Source:Diabetes & Metabolism
      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: 2014-12-24T04:56:57Z
       
  • Polymerase chain reaction–denaturing gradient gel electrophoresis
           (PCR–DGGE): A promising tool to diagnose bacterial infections in
           diabetic foot ulcers
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6
      Author(s): C. Dunyach-Remy , A. Cadière , J.-L. Richard , S. Schuldiner , S. Bayle , B. Roig , A. Sotto , J.-P. Lavigne
      Aim The diagnosis of diabetic foot infections is difficult due to limitations of conventional culture-based techniques. The objective of this study was to evaluate the contribution of denaturing gradient gel electrophoresis (DGGE) in the microbiological diagnosis of diabetic foot ulcers in comparison to conventional techniques, and also to evaluate the need to perform a biopsy sample for this diagnosis. Methods Twenty diabetic patients (types 1 and 2) with foot ulcers (grades 1–4) were included. After debridement of their wounds, samples were taken in duplicate by surface swabbing and deep-tissue biopsy. The samples were analyzed by conventional culture and by a new molecular biology tool, DGGE technology. Results Polymerase chain reaction (PCR)–DGGE led to the identification of more bacteria than did conventional cultures (mean: 2.35 vs 0.80, respectively). In 11 cases, the technology detected pathogenic species not isolated by classical cultures. PCR–DGGE also identified significantly more pathogenic species at deep levels compared with species detected at superficial levels (87% vs 58%, respectively; P =0.03). In 9/20 cases, pathogenic bacteria were detected only in deep samples, revealing the need to perform tissue biopsy sampling. Conclusion DGGE, achievable in 48h, could be a useful technique for the bacteriological diagnosis of diabetic foot infections. It may help to identify pathogenic bacteria in deeply infected ulcers, thereby contributing to a more appropriate use of antibiotics.


      PubDate: 2014-12-20T03:34:28Z
       
  • Association between metabolically unhealthy overweight/obesity and chronic
           kidney disease: The role of inflammation
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6
      Author(s): S. Chen , S. Zhou , B. Wu , Y. Zhao , X. Liu , Y. Liang , X. Shao , H. Holthöfer , H. Zou
      Aim Our study explored the association between subtypes of increased fat mass (with or without associated metabolic alterations) and the presence of chronic kidney disease (CKD). Methods In this cross-sectional survey in China, body mass index (BMI) was used to assess fat mass. Metabolically healthy was defined as no insulin resistance or any metabolic syndrome components except abdominal obesity. We also used two previous definitions of metabolically healthy. Multiple logistic regression models were used. Normal weight with metabolic health was designated the reference group. Three other subgroups included normal weight with metabolic unhealthiness, overweight/obesity with metabolic health and overweight/obesity with metabolic unhealthiness. Results Of the 2324 subjects, 11.77% overweight/obese subjects were metabolically healthy. Compared with normal-weight subjects who were metabolically healthy, overweight/obese subjects who were metabolically healthy did not have an increased risk of CKD (OR: 0.79, 95% CI: 0.29–2.14; P =0.64), whereas overweight/obese subjects who were metabolically unhealthy had a significantly higher risk of CKD (OR: 2.47, 95% CI: 1.5–3.95; P <0.001). Normal-weight subjects who were metabolically unhealthy also had a higher risk of CKD, but the P value was of borderline significance. On further adjusting for C-reactive protein (CRP) levels, ORs were much attenuated, but did not alter the associations observed. Using two other definitions of metabolically healthy resulted in similar results. Conclusion Metabolically unhealthy overweight/obesity, but not metabolically healthy overweight/obesity, is associated with an increased risk of CKD. Inflammation might mediate at least part of the association between metabolic changes and CKD prevalence.


      PubDate: 2014-12-20T03:34:28Z
       
  • Incretin-based therapy and pancreatic beta cells
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6
      Author(s): S. Chon , J.-P. Riveline , B. Blondeau , J.-F. Gautier
      Type 2 diabetes (T2D) is a complex, progressive disease with life-threatening complications and one of the most serious public-health problems worldwide. The two main mechanisms of T2D pathogenesis are pancreatic beta cell dysfunction and insulin resistance. It is now recognized that pancreatic beta cell dysfunction is a necessary factor for T2D development. Traditional therapies for controlling blood glucose are suboptimal as they fail to meet target goals for many patients. Glucagon-like peptide-1 receptor agonists (GLP1RA) and dipeptidyl peptidase-4 inhibitors (DPP4I) are an attractive class of therapy because they reduce blood glucose by targeting the incretin hormone system and, in particular, have the potential to positively affect pancreatic beta cell biology. This review outlines our current understanding of pancreatic beta cell incretin system dysfunction in T2D and summarizes recent evidence of the effect of incretin-based therapies on beta cell function and mass. Incretin-based therapies have shown strong evidence for beneficial effects on beta cell function and mass in animal studies. In humans, incretin-based therapies are effective glucose-lowering agents, but further study is still required to evaluate their long-term effects on beta cell function and safety as well as beta cell mass expansion.


      PubDate: 2014-12-20T03:34:28Z
       
  • Molecular mechanisms of GLUT4 regulation in adipocytes
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6
      Author(s): R. Govers
      Insulin resistance is strongly linked to type 2 diabetes and associated with a reduced uptake of glucose by muscle and adipose tissue. The transporter that is responsible for this uptake and whose function is disturbed in insulin resistance and type 2 diabetes is GLUT4. In the non-stimulated state, GLUT4 is efficiently sequestered intracellularly. This retention prevents GLUT4 from reaching the cell surface and transporting glucose into muscle and fat cells when blood glucose levels are low. After a meal when blood glucose levels rise, insulin is secreted by the pancreas, which, upon binding to its receptor, triggers an intracellular signaling cascade, leading to the translocation of GLUT4 from intracellular compartments to the cell surface, resulting in glucose uptake and normalization of the blood glucose levels. Its regulation is dominated by its localization, efficient intracellular retention and sensitivity to insulin and contraction, which makes GLUT4 an interesting and unique molecule. These aspects of the intracellular regulation of GLUT4 are described in this review.


      PubDate: 2014-12-20T03:34:28Z
       
  • Liraglutide treatment in a patient with HIV, type 2 diabetes and sleep
           apnoea–hypopnoea syndrome
    • Abstract: Publication date: Available online 6 November 2014
      Source:Diabetes & Metabolism
      Author(s): M.D. García de Lucas , J. Olalla Sierra , J. Piña Fernández



      PubDate: 2014-12-20T03:34:28Z
       
  • The impact of hyperfiltration on the diabetic kidney
    • Abstract: Publication date: Available online 18 November 2014
      Source:Diabetes & Metabolism
      Author(s): E. Premaratne , S. Verma , E.I. Ekinci , G. Theverkalam , G. Jerums , R.J. MacIsaac
      More than two decades ago, hyperfiltration (HF) in diabetes was postulated to be a maladaptive response observed early in the course of diabetic kidney disease (DKD), which may eventually predispose to irreversible damage to nephrons and development of progressive renal disease. Despite this, the potential mechanisms leading to renal HF in diabetes are not fully understood, although several hypotheses have been proposed, including alterations in glomerular haemodynamic function and tubulo-glomerular feedback. Furthermore, the role of HF as a causative factor in renal disease progression is still unclear and warrants further prospective longer-term studies. Although HF has been entrenched as the first stage in the classic albuminuric pathway to end-stage renal disease in DKD, and HF has been shown to predict the progression of albuminuria in many, but not all studies, the concept that HF predisposes to the development of chronic kidney disease (CKD) stage 3, that is, glomerular filtration rate (GFR) decline to<60mL/min/1.73m2, remains to be proved. Further long-term studies of GFR gradients therefore are required to establish whether HF ultimately leads to decreased kidney function, after adjustment for glycaemic control and other confounders. Whether reversal of HF with therapeutic agents is protective against reducing the risk of development of albuminuria and renal impairment is also worth investigating in prospective randomized trials.


      PubDate: 2014-12-20T03:34:28Z
       
  • Endocrine disruptors: New players in the pathophysiology of type 2
           diabetes'
    • Abstract: Publication date: Available online 20 November 2014
      Source:Diabetes & Metabolism
      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: 2014-12-20T03:34:28Z
       
  • 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: Available online 24 November 2014
      Source:Diabetes & Metabolism
      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 ClinicalTrials.gov: NCT01628341.


      PubDate: 2014-12-20T03:34:28Z
       
  • Use of insulin in type 2 diabetes: What we learned from recent clinical
           trials on the benefits of early insulin initiation
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6
      Author(s): M. Hanefeld
      The majority of people with type 2 diabetes mellitus (T2DM) require insulin therapy to maintain HbA1c levels<7% during the first decade of diagnosis. Large prospective trials investigating the cardiovascular (CV) benefits of intensive glycaemic control have produced inconsistent results; however, meta-analyses have suggested that intensive glycaemic control provides both micro- and macrovascular benefits. The ORIGIN study investigated the impact of basal insulin glargine therapy targeting ≤ 5.3mmol/L for fasting plasma glucose compared with standard care on CV outcomes in people with pre- or early diabetes, and demonstrated a neutral effect on CV outcomes with long-term use of insulin glargine early in the course of diabetes, with a low rate of severe hypoglycaemia and modest weight gain. The EARLY, GLORY and EASIE studies also demonstrated that insulin use earlier in the treatment pathway led to improved glycaemic control, reduced weight gain and fewer hypoglycaemic episodes than when insulin was added later in the course of disease. The beneficial effect of early transient intensive insulin therapy (TIIT) at diagnosis has been demonstrated in a number of trials; it rapidly limits the damage caused by gluco- and lipotoxicity, improving residual β-cell function and potentially slowing disease progression. The evidence suggests that people newly diagnosed with T2DM and HbA1c >9% should be given early TIIT to achieve normoglycaemia within weeks, after which standard care should then be adopted. Insulin use earlier in the treatment pathway should be considered, as it reduces the risk of hypoglycaemia as well as allows β-cell rest, which can help preserve β-cell function.


      PubDate: 2014-12-20T03:34:28Z
       
  • 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: Available online 4 December 2014
      Source:Diabetes & Metabolism
      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: 2014-12-20T03:34:28Z
       
  • Potential risks associated with increased plasma plant-sterol levels
    • Abstract: Publication date: Available online 9 December 2014
      Source:Diabetes & Metabolism
      Author(s): B. Vergès , F. Fumeron
      The consumption of plant sterols is associated with a decrease in LDL cholesterol. However, it is also associated with an increase in plasma plant-sterol (sitosterol, campesterol) levels that may be detrimental. Indeed, the genetic disease sitosterolaemia, which is characterized by elevated plasma levels of plant sterol, is associated with premature atherosclerosis. Yet, although plasma plant-sterol levels are recognized markers of cholesterol absorption, the relationship between such levels and atherosclerosis is not clear. Several studies have analysed the association between plasma plant-sterol levels and cardiovascular disease (CVD), but have found conflicting results. Although the largest prospective trials and genome-wide association studies suggest that high plasma levels of plant sterols are associated with increased CV risk, other studies have reported no such association and even an inverse relationship. Thus, the available data cannot confirm an increased CV risk with plant sterols, but cannot rule it out either. Only a prospective interventional trial to analyse the effects of plant-sterol-enriched food on the occurrence of CV events can exclude a potential CV risk linked with their consumption.


      PubDate: 2014-12-20T03:34:28Z
       
  • Effect of phytosterols/stanols on LDL concentration and other surrogate
           markers of cardiovascular risk
    • Abstract: Publication date: Available online 9 December 2014
      Source:Diabetes & Metabolism
      Author(s): J.-M. Bard , F. Paillard , J.-M. Lecerf
      Plant sterols and stanols are well-known to reduce LDL-cholesterol (LDL-C) concentrations. It is generally accepted that supplementation with 2g/day of sterols/stanols leads to a 10% reduction in LDL. However, most of the clinical trials supporting this conclusion were of short-term duration, and the results of longer interventions are scanty. In four studies, interventions lasting>6 months were carried out and the LDL-C-lowering effects were maintained over this longer duration, although some results suggest that a reduced effect may be observed with sterols, while stanols maintain their effect. In any case, the data are too limited to be definitive. In a free-living population as well as in multiparametric interventional studies, however, the LDL-C-lowering effect has been confirmed, although to a lesser extent than in clinical studies. In the absence of data on cardiovascular morbidity and mortality, data for surrogate markers of cardiovascular risk could be considered adequate alternatives. Several studies have been conducted on this basis, but their results failed to demonstrate any favourable effects. The present report summarizes the different results obtained in long-term studies, and in those comparing the effects of sterols and stanols on lipids and other surrogate markers of cardiovascular risk.


      PubDate: 2014-12-20T03:34:28Z
       
  • Ten-year improvement of insulin resistance and growth with recombinant
           human insulin-like growth factor 1 in a patient with insulin receptor
           mutations resulting in leprechaunism
    • Abstract: Publication date: Available online 25 November 2014
      Source:Diabetes & Metabolism
      Author(s): M. de Kerdanet , M. Caron-Debarle , S. Nivot , T. Gaillot , O. Lascols , B. Fremont , M. Bonaure , S. Gie , C. Massart , J. Capeau
      Aim Leprechaunism, a rare genetic disease resulting from mutations in two alleles of the insulin receptor gene, is characterized by severe insulin resistance, retarded growth and, usually, premature death. The ability of treatment with recombinant human insulin-like growth factor 1 (rhIGF1) to improve metabolic and clinical parameters in the long-term is still controversial. Methods Mutations were looked for in the insulin receptor gene of a four-month-old female baby with leprechaunism. The patient's skin fibroblasts were analyzed for response to insulin and IGF1. At the clinical level, the very long-term effects of treatment with rhIGF1/rhIGFBP3 were evaluated by clinical and metabolic parameters. Results The patient's diagnosis was based on compound heterozygous mutations in two alleles of the insulin receptor gene, thus confirming leprechaunism. Cultured fibroblasts showed a decreased number of insulin receptors and were insulin-resistant. However, IGF1 was able to stimulate IGF1 receptor signalling, suggesting possible activation of a salvage pathway. Treatment with IGF1/IGFBP3 for 8.7years, then IGF1 for 2years, resulted in normalization of circulating levels of IGF1 and IGFBP3. Large daily variations in glycaemia and insulinaemia persisted, but mean glycaemia decreased. Regarding growth, the patient's BMI Z score normalized and length/height score improved. Our patient presented normal neurological development and academic achievement. The treatment was free of adverse effects. Conclusion Our results provide evidence that rhIGF1 with and without rhIGFBP3 can prevent fatal outcomes, and improve growth and metabolic parameters, for more than 10years in a patient with leprechaunism. Long-term rhIGF1 for severe insulin resistance syndrome should be considered.


      PubDate: 2014-12-20T03:34:28Z
       
  • Switching from insulin glargine to insulin degludec reduced HbA1c, daily
           insulin doses and anti-insulin antibody in anti-insulin antibody-positive
           subjects with type 1 diabetes
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6
      Author(s): H. Hamasaki , H. Yanai



      PubDate: 2014-12-20T03:34:28Z
       
  • Acylated-based long-acting insulin analogues: Is “misfolding”
           the problem' Commentary letter on Hamasaki H and Yanai H. The
           switching from insulin glargine to insulin degludec reduced HbA1c, daily
           insulin doses and anti-insulin antibody in anti-insulin antibody-positive
           subjects with type 1 diabetes
    • Abstract: Publication date: December 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 6
      Author(s): L. Monnier , C. Colette , D. Owens



      PubDate: 2014-12-20T03:34:28Z
       
  • New insights on glucose homoeostasis during Ramadan
    • Abstract: Publication date: Available online 15 December 2014
      Source:Diabetes & Metabolism
      Author(s): L. Monnier , F. Bonnet , C. Colette



      PubDate: 2014-12-20T03:34:28Z
       
  • Glucose excursions and glycaemic control during Ramadan fasting in
           diabetic patients: Insights from continuous glucose monitoring (CGM)
    • Abstract: Publication date: Available online 10 December 2014
      Source:Diabetes & Metabolism
      Author(s): N. Lessan , Z. Hannoun , H. Hasan , M.T. Barakat
      Aim Ramadan fasting represents a major shift in meal timing and content for practicing Muslims. This study used continuous glucose monitoring (CGM) to assess changes in markers of glycaemic excursions during Ramadan fasting to investigate the short-term safety of this practice in different groups of patients with diabetes. Methods A total of 63 subjects (56 with diabetes, seven healthy volunteers; 39 male, 24 female) had CGM performed during, before and after Ramadan fasting. Mean CGM curves were constructed for each group for these periods that were then used to calculate indicators of glucose control and excursions. Post hoc data analyses included comparisons of different medication categories (metformin/no medication, gliptin, sulphonylurea and insulin). Medication changes during Ramadan followed American Diabetes Association guidelines. Result Among patients with diabetes, there was a significant difference in mean CGM curve during Ramadan, with a slow fall during fasting hours followed by a rapid rise in glucose level after the sunset meal (iftar). The magnitude of this excursion was greatest in the insulin-treated group, followed by the sulphonylurea-treated group. Markers of control deteriorated in a small number (n =3) of patients. Overall, whether fasting or non-fasting, subjects showed no statistically significant changes in mean interstitial glucose (IG), mean amplitude of glycaemic excursion (MAGE), high and low blood glucose indices (HBGI/LBGI), and number of glucose excursions and rate of hypoglycaemia. Conclusion The main change in glycaemic control with Ramadan fasting in patients with diabetes is in the pattern of excursions. Ramadan fasting caused neither overall deterioration nor improvement in the majority of patients with good baseline glucose control.


      PubDate: 2014-12-20T03:34:28Z
       
  • Screening for gestational diabetes in the Lombardy region: A
           population-based study
    • Abstract: Publication date: Available online 16 December 2014
      Source:Diabetes & Metabolism
      Author(s): F. Nicotra , C. Molinari , N. Dozio , M.T. Castiglioni , B. Ibrahim , A. Zambon , G. Corrao , M. Scavini
      Aim As the treatment of hyperglycaemia during pregnancy with diet or insulin reduces the risk of adverse maternal outcomes and perinatal complications, screening for gestational diabetes mellitus (GDM) is included, albeit to variable extents, in all guidelines of care for pregnant women. The aim of the present investigation was to estimate the proportion of pregnancies screened for GDM in Lombardy between 2007 and 2010, and to identify predictors of screening. Methods A retrospective cross-sectional study using regional healthcare utilization databases of Lombardy was conducted. The study included all residents of Lombardy without pregestational diabetes who delivered between 1 January 2007 and 31 December 2010. The proportion of pregnancies with at least one screening test for GDM was calculated, along with the odds ratios and 95% confidence intervals associated with selected covariates for GDM screening. Results Of the 362,818 pregnancies included in the sample, 30% were screened for GDM. The proportion of pregnancies screened increased slightly from 2007 (27%) to 2010 (33%) and with maternal age (from 28% among women<25 years to 32% among those ≥35years), and varied widely across local health management organizations (HMOs) of residence (range: 20% to 68%). Socioeconomic indicators (education, immigrant status), obstetric history and prepregnancy hypertension were independent predictors of GDM screening. Conclusion The study finding of a low rate of pregnant women screened for GDM among residents of Lombardy supports the need for programmes to improve training of healthcare professionals, to raise women's awareness of GDM and to eliminate barriers to GDM screening.


      PubDate: 2014-12-20T03:34:28Z
       
  • Clinical utility of serum beta-2-microglobulin as a predictor of diabetic
           complications in patients with type 2 diabetes without renal impairment
    • Abstract: Publication date: Available online 7 October 2014
      Source:Diabetes & Metabolism
      Author(s): M.K. Kim , K.-J. Yun , H.J. Chun , E.-H. Jang , K.-D. Han , Y.-M. Park , K.-H. Baek , K.-H. Song , B.-Y. Cha , C.S. Park , H.-S. Kwon
      Aim As serum beta-2-microglobulin (B2M) levels are usually elevated in patients with renal failure, they have been suggested as a surrogate marker of cardiovascular mortality for patients with chronic kidney disease. Glycation of B2M is cytotoxic and may contribute to the risk of diabetic complications in patients with diabetes. Our objective was to evaluate the relationship between B2M and diabetic complications in patients with type 2 diabetes (T2D) and normal kidney function. Methods A total of 366 patients with T2D and preserved renal function with no clinical evidence of cardiovascular disease were enrolled consecutively into this study. High B2M was defined as a median serum B2M level ≥ 1.8mg/L. Subclinical atherosclerosis was defined as a carotid artery intima–media thickness (C-IMT) ≥ 0.9mm or the presence of carotid plaque. The definition of diabetic nephropathy was based on the presence of albuminuria (≥ 30mg/g creatinine). Results Patients with high B2M were older, and had diabetes of longer duration, higher serum creatinine, microalbuminuria, and increased vascular stiffness and C-IMT compared with patients with low B2M. B2M levels were positively correlated with C-IMT and vascular stiffness, and these associations remained constant after adjusting for age. In addition, after adjusting for age, gender, body mass index, serum creatinine, hypertension, smoking and alcohol consumption, the adjusted odds ratio (OR) for atherosclerosis was 2.01 [95% confidence interval (CI): 1.02–3.94] per 1mg/L increase in B2M. The prevalences of diabetic retinopathy and nephropathy were significantly higher with a high B2M than with a low B2M. The multiple adjusted OR for diabetic nephropathy was 2.29 (95% CI: 1.11–4.72) per 1mg/L increase of B2M. Conclusion Higher serum B2M was an independent risk factor for subclinical atherosclerosis and diabetic nephropathy in patients with T2D without renal impairment.


      PubDate: 2014-10-10T03:22:03Z
       
  • Perceived psychosocial stress and glucose intolerance among pregnant
           Hispanic women
    • Abstract: Publication date: Available online 16 June 2014
      Source:Diabetes & Metabolism
      Author(s): M.L. Silveira , B.W. Whitcomb , P. Pekow , B. Braun , G. Markenson , N. Dole , J.E. Manson , C.G. Solomon , E.T. Carbone , L. Chasan-Taber
      Aim Prior literature suggests a positive association between psychosocial stress and the risk of diabetes in non-pregnant populations, but studies during pregnancy are sparse. We evaluated the relationship between stress and glucose intolerance among 1115 Hispanic (predominantly Puerto Rican) prenatal care patients in Proyecto Buena Salud, a prospective cohort study in Western Massachusetts (2006–2011). Methods Cohen's Perceived Stress Scale (PSS-14) was administered in early (mean=12.3weeks gestation; range 4.1–18weeks) and mid- (mean=21.3weeks gestation; range 18.1–26weeks) pregnancy. Participants were classified as having a pregnancy complicated by gestational diabetes mellitus, impaired glucose tolerance, and abnormal glucose tolerance, based on the degree of abnormality on glucose tolerance testing between 24 and 28weeks of gestation. Results The prevalence of gestational diabetes mellitus, impaired glucose tolerance, and abnormal glucose tolerance was 4.1%, 7.2%, and 14.5%, respectively. Absolute levels of early or mid-pregnancy stress were not significantly associated with glucose intolerance. However, participants with an increase in stress from early to mid-pregnancy had a 2.6-fold increased odds of gestational diabetes mellitus (95% confidence intervals: 1.0–6.9) as compared to those with no change or a decrease in stress after adjusting for age and pre-pregnancy body mass index. In addition, every one-point increase in stress scores was associated with a 5.5mg/dL increase in screening glucose level (β=5.5; standard deviation=2.8; P =0.05), after adjusting for the same variables. Conclusion In this population of predominantly Puerto Rican women, stress patterns during pregnancy may influence the risk of glucose intolerance.


      PubDate: 2014-06-27T16:48:13Z
       
  • Insights from a thermography-based method suggesting higher carotid
           inflammation in patients with diabetes mellitus and coronary artery
           disease
    • Abstract: Publication date: Available online 26 June 2014
      Source:Diabetes & Metabolism
      Author(s): K. Toutouzas , G. Benetos , M. Drakopoulou , P. Bounas , D. Tsekoura , K. Stathogiannis , I. Koutagiar , C. Aggeli , A. Karanasos , D. Panagiotakos , E. Siores , C. Stefanadis
      Aim Diabetes mellitus (DM) is an independent risk factor for stroke. In a DM population, carotid atheromatosis is a major cause of stroke. The role of carotid plaque inflammation remains conflicting. Microwave radiometry (MWR) is a new non-invasive method allowing in vivo measurement of the temperature of tissues, so reflecting inflammation. The aim of this prospective study was to evaluate the impact of DM on carotid artery inflammation in patients with documented coronary artery disease (CAD). Methods Consecutive patients (n =300) with significant CAD were evaluated by: (1) ultrasound study of both carotid arteries; and (2) the temperature difference (ΔT) along each carotid artery on MWR. ΔT≥0.90°C was considered high ΔT. Vessel- and patient-based analyses were performed to determine the impact of DM on morphological and functional characteristics of carotid arteries. Results Out of 300 patients, 113 (37.7%) had DM. Patients with DM had similar carotid plaque thickness compared with patients without DM in both vessel- and patient-based analyses. In contrast, patients with DM exhibited higher ΔT values in both vessel- and patient-based analyses. On multivariate logistic regression analysis, DM was an independent predictor of high ΔT both unilaterally and bilaterally (OR: 1.66, 95% CI: 1.06–2.58, P =0.03 and OR: 1.96, 95% CI: 1.01–3.81, P =0.05, respectively). Conclusion In patients with CAD, DM was an independent predictor of local carotid plaque inflammatory activation. Whether or not the assessment of functional plaque characteristics by MWR can be an additional prognostic tool independent of structural factors now needs to be further investigated.


      PubDate: 2014-06-27T16:48:13Z
       
  • Serum and intraocular concentrations of erythropoietin and vascular
           endothelial growth factor in patients with type 2 diabetes and
           proliferative retinopathy
    • Abstract: Publication date: Available online 27 May 2014
      Source:Diabetes & Metabolism
      Author(s): F. Semeraro , A. Cancarini , F. Morescalchi , M.R. Romano , R. dell’Omo , G. Ruggeri , L. Agnifili , C. Costagliola
      Aim This study compared systemic and intraocular concentrations of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in patients with type 2 diabetes (T2D) and proliferative diabetic retinopathy (PDR) with levels in patients without diabetes, and looked for possible correlations between the concentrations found and other variables analyzed. Methods Concentrations of EPO and VEGF were measured in the aqueous and vitreous humours and serum of patients undergoing vitrectomy for PDR (33 patients) or for macular holes or puckers (20 control patients). EPO was assayed by radioimmunoassay, with a lower limit of detection (LOD) of 1.0 mIU/mL. VEGF was assayed using enzyme-linked immunosorbent assay (ELISA), with a lower LOD of 10.0pg/mL. Results EPO concentrations in serum did not differ significantly between the two groups, whereas EPO in vitreous and aqueous were higher in diabetic than in non-diabetic patients. VEGF in serum was lower in diabetic patients than in non-diabetics; conversely, VEGF concentrations in vitreous were significantly higher in diabetic patients. A direct correlation was found between vitreous and aqueous EPO concentrations, and between vitreous EPO and blood glucose concentrations. A significant, negative correlation between vitreous EPO concentration and age was also recorded. Conclusion High EPO concentrations in the vitreous of patients with PDR and its correlation with blood glucose suggest that EPO could play a role in the pathogenesis of PDR. All possible factors affecting serum and ocular concentrations of EPO and VEGF should be determined to identify compounds able to prevent and control this serious microvascular complication of diabetes.


      PubDate: 2014-06-01T14:24:10Z
       
  • Association of endothelial lipase Thr111Ile polymorphism with
           proliferative retinopathy in type 2 diabetes patients
    • Abstract: Publication date: Available online 19 May 2014
      Source:Diabetes & Metabolism
      Author(s): C. Arndt , I. Leclercq , P. Nazeyrollas , A. Durlach , A. Ducasse , I. Movesayan , E. Socquard , C. Clavel , M.M. Malloy , C.R. Pullinger , J.P. Kane , V. Durlach
      Aim Our previous study demonstrated that the endothelial lipase (EL) C.584C>T polymorphism (rs2000813, p.Thr111Ile) was significantly associated with diabetic retinopathy (DR). The present work was conducted to see if this specific variant of the EL gene was more specifically linked to the severity of DR. Methods This retrospective cohort study was based on a review of the institutional charts of 287 type 2 diabetes patients (mean age=59.7years; mean BMI=29.0kg/m2; mean HbA1c =8.4%) genotyped for the EL C.584C>T polymorphism (rs2000813, p.Thr111Ile). The stage of DR was also determined for each genotype (CC, CT, TT). Results On univariate analysis, the minor allele homozygote TT variant was significantly associated with severe DR (OR: 4.3; 95% CI: 1.4, 13.1) compared with the major CC homozygote. No significant result was found for the CT heterozygote. Multivariate analysis revealed an increased risk for TT homozygotes to present with severe non-proliferative DR (OR: 8.09; 95% CI: 1.23, 53.1) or proliferative DR. Other associations were not significant. Conclusion Minor allele homozygosity for this EL variant (c.584C>T) could be a significant risk factor for developing severe, sight-threatening disease due to proliferative DR. Further prospective studies of this EL polymorphism in a larger population sample are needed to confirm these results.


      PubDate: 2014-05-25T16:16:38Z
       
  • Serum sex steroids and steroidogenesis-related enzyme expression in
           skeletal muscle during experimental weight gain in men
    • Abstract: Publication date: Available online 30 April 2014
      Source:Diabetes & Metabolism
      Author(s): K. Sato , D. Samocha-Bonet , D.J. Handelsman , S. Fujita , G.A. Wittert , L.K. Heilbronn
      Objectives Low-circulating testosterone is associated with development of type 2 diabetes in obese men. In this study, we examined the effects of experimental overfeeding and weight gain on serum levels of sex hormones and skeletal muscle expression of steroidogenic enzymes in healthy men with (FH+) and without (FH–) a family history of type 2 diabetes. Methods Following a 3-day lead in energy balanced diet, FH+ (n =9) and FH– men (n =11) were overfed by 5200kJ/day (45% fat) for 28days. Body weight, fasting glucose, insulin, sex steroid, sex hormone binding globulin (SHBG) levels, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and body fat (DXA) were assessed in all individuals at baseline and day28, and sex steroidogenesis-related enzyme expression in vastus lateralis biopsies was examined in a subset (n =11). Results Body weight, fat mass and fasting insulin levels were increased by overfeeding (P <0.01) and insulin was increased significantly more in FH+ men (P <0.01). Serum sex hormone binding globulin (SHBG) and 5α-dihydrotestosterone (DHT) were reduced with overfeeding (P <0.05), and serum testosterone and DHT were reduced to a greater extent in FH+ men (P <0.05). Overfeeding reduced mRNA expression of 3β-hydroxysteroid dehydrogenase (HSD) and 17βHSD (P ≤0.007), independently of group. 5α-Reductase (SRD5A1) mRNA expression was not changed overall, but a time by group interaction was observed (P =0.04). Conclusion Overfeeding reduced SHBG and muscle expression of enzymes involved in the formation of testosterone in skeletal muscle. Men with a family history of T2DM were more susceptible to deleterious outcomes of overfeeding with greater reductions in serum testosterone and DHT and greater increases in markers of insulin resistance, which may contribute to increased risk of developing type 2 diabetes.


      PubDate: 2014-05-05T11:18:02Z
       
 
 
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