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Journal Cover Diabetes & Metabolism
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     ISSN (Print) 1262-3636
     Published by Elsevier Homepage  [2566 journals]   [SJR: 0.871]   [H-I: 56]
  • Strong correlation between glycaemic variability and total glucose
           exposure in type 2 diabetes is limited to subjects with satisfactory
           glycaemic control
    • Abstract: Publication date: September 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 4
      Author(s): S. Suh , J.Y. Joung , S.M. Jin , M.Y. Kim , J.C. Bae , H.D. Park , M.S. Lee , M.K. Lee , J.H. Kim
      Aims This study investigated the relationship between markers of overall glucose exposure, postprandial glucose excursions and glycaemic variability in patients with type 2 diabetes mellitus (T2DM). Methods A total of 63 patients with T2DM (mean age 56 years) were enrolled. All wore a continuous glucose monitoring system (CGMS) device for 72h to collect data on markers of overall glucose exposure, postprandial glucose excursions and glycaemic variability parameters. Results Spearman's correlation analysis revealed significant correlations between all markers of overall glucose exposure and various parameters related to glucose excursions. The percent coefficient of variation (CV) showed the strongest correlation with glycated albumin (r =0.470, P <0.01). In participants with HbA1c levels<7.5% (n =33), almost all glycaemic markers and glycaemic variability parameters were significantly correlated with each other. Also, all postprandial glucose excursion parameters showed significant correlation with other glycaemic markers, and all markers of overall glucose exposure were significantly related to mean glucose, postprandial glucose excursions and glycaemic variability parameters (except CV). In contrast, in participants with HbA1c levels≥7.5% (n =30), no parameters of postprandial glucose excursions and glycaemic variability were related to any markers of chronic glycaemia. Conclusion Postprandial glucose excursions may explain glycaemic variability and total glucose exposures in well-controlled T2DM patients.


      PubDate: 2014-09-17T23:57:58Z
       
  • Prevention of unhealthy weight in children by promoting physical activity
           using a socio-ecological approach: What can we learn from intervention
           studies?
    • Abstract: Publication date: September 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 4
      Author(s): N. Kellou , F. Sandalinas , N. Copin , C. Simon
      Aim Our objectives was to identify the characteristics of interventions likely to successfully prevent overweight in youngsters by promoting physical activity (PA), with special focus on dimensions of the socio-ecological model of behaviour and health, and unresolved issues. Methods This was a systematic review of population-based interventions either promoting PA or limiting sedentary behaviour in children with measure of weight status as an endpoint. The efficacy of studies was evaluated according to the levels of PA determinants in the socio-ecological model (individual, interpersonal, institutional environment, community) targeted by the interventions. Results A total of 54 studies met our inclusion criteria, most of them published within the last 5years and targeting children aged 6–12years. Twenty-three interventions targeted individual and/or interpersonal PA determinants only; 26 targeted determinants at three or four levels with at least one environment component at the institutional level; and five were multilevel community-based interventions. Our review indicated that programmes targeting PA determinants at the different levels of the socio-ecological model, including the social and organizational/built environments, had the greatest potential for preventing obesity in youngsters. Targeting various facets of PA, including everyday PA, might represent another key element for program efficacy on weight status. Conclusion Data regarding the efficacy of comprehensive PA interventions that simultaneously address individual attitudes and skills, the social context, and the environment, to prevent overweight in children are encouraging. Further studies are needed to evaluate the maintenance of the effects and whether such strategies apply to young children and older adolescents, and to different cultural contexts.


      PubDate: 2014-09-17T23:57:58Z
       
  • Editorial Board
    • Abstract: Publication date: September 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 4




      PubDate: 2014-09-17T23:57:58Z
       
  • Clinical inertia, uncertainty and individualized guidelines
    • Abstract: Publication date: September 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 4
      Author(s): G. Reach
      Doctors often do not follow the guidelines of good practice based on evidence-based medicine, and this “clinical inertia” may represent an impediment to efficient care. The aims of this article are as follows: 1) to demonstrate that this phenomenon is often the consequence of a discrepancy between the technical rationality of evidence-based medicine and the modes of reasoning of physicians practiced in “real-life”, which is marked by uncertainty and risk; 2) to investigate in this context the meaning of the recent, somewhat paradoxical, concept of “individualized guidelines”; and 3) to revisit the real, essentially pedagogical, place of guidelines in medical practice.


      PubDate: 2014-09-17T23:57:58Z
       
  • Glucose metabolism: Focus on gut microbiota, the endocannabinoid system
           and beyond
    • Abstract: Publication date: September 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 4
      Author(s): P.D. Cani , L. Geurts , S. Matamoros , H. Plovier , T. Duparc
      The gut microbiota is now considered as a key factor in the regulation of numerous metabolic pathways. Growing evidence suggests that cross-talk between gut bacteria and host is achieved through specific metabolites (such as short-chain fatty acids) and molecular patterns of microbial membranes (lipopolysaccharides) that activate host cell receptors (such as toll-like receptors and G-protein-coupled receptors). The endocannabinoid (eCB) system is an important target in the context of obesity, type 2 diabetes (T2D) and inflammation. It has been demonstrated that eCB system activity is involved in the control of glucose and energy metabolism, and can be tuned up or down by specific gut microbes (for example, Akkermansia muciniphila). Numerous studies have also shown that the composition of the gut microbiota differs between obese and/or T2D individuals and those who are lean and non-diabetic. Although some shared taxa are often cited, there is still no clear consensus on the precise microbial composition that triggers metabolic disorders, and causality between specific microbes and the development of such diseases is yet to be proven in humans. Nevertheless, gastric bypass is most likely the most efficient procedure for reducing body weight and treating T2D. Interestingly, several reports have shown that the gut microbiota is profoundly affected by the procedure. It has been suggested that the consistent postoperative increase in certain bacterial groups such as Proteobacteria, Bacteroidetes and Verrucomicrobia (A. muciniphila) may explain its beneficial impact in gnotobiotic mice. Taken together, these data suggest that specific gut microbes modulate important host biological systems that contribute to the control of energy homoeostasis, glucose metabolism and inflammation in obesity and T2D.


      PubDate: 2014-09-17T23:57:58Z
       
  • Impact of flexible insulin therapy on blood glucose variability, oxidative
           stress and inflammation in type 1 diabetic patients: The VARIAFIT study
    • Abstract: Publication date: September 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 4
      Author(s): P.Y. Benhamou , F. Somers , S. Lablanche , I. Debaty , A.L. Borel , L. Nasse , F. Stanke-Labesque , P. Faure , R. Boizel , S. Halimi
      Aims HbA1c only partially predicts vascular risk in patients with type 1 diabetes (T1D), and a role for blood glucose variability (BGV) is a matter of debate. For this reason, this study investigated the impact of an educational programme of flexible insulin therapy (FIT) on BGV and oxidative stress. Methods Tests were conducted on 30 adult T1D patients in a prospective, single-centre trial at baseline (M0), and at 3 and 6months (M3 and M6, respectively) of the FIT programme to determine BGV, as reflected by mean amplitude of glycaemic excursions (MAGE), low blood glucose index (LBGI), lability index (LI), average daily risk range (ADRR), glycaemic lability (scored by two diabetologists), urinary leukotriene E4 (LTE4), 11-dehydro-thromboxane B2 (TXB2) and 8-iso-prostaglandin F2α (PGF2). Results HbA1c (7.7±0.9%), ADRR, MAGE, LBGI and LI did not change from M0 to M3 and M6, although ADRR and LBGI significantly improved at M3 and M6 in patients with the highest baseline indices (≥ 40 and ≥ 5, respectively). TXB2 declined at M6 (832±625 vs. 633±972pg/mg; P =0.048), whereas LTE4 and PGF2 remained stable. ADRR showed the strongest correlation with glycaemic lability scores at all visits (r ≥0.84, P <0.0001). Conclusion A FIT educational programme improved BGV only in patients with the highest baseline variability, and led to no changes in HbA1c, while ADRR closely correlated with glycaemic lability score. Our data do not support a relationship between BGV and oxidative stress in T1D patients, although the impact of variability on TXB2 deserves further investigation (ClinicalTrials.gov NCT00973492).


      PubDate: 2014-09-17T23:57:58Z
       
  • Food insecurity in French patients with diabetes
    • Abstract: Publication date: September 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 4
      Author(s): S. Pilot , R. Cohen , G. Reach , E. Cosson , H. Le Clesiau , S. Hercberg , H. Bihan



      PubDate: 2014-09-17T23:57:58Z
       
  • A novel heterozygous mutation in the glucokinase gene conferring
           exercise-induced symptomatic hyperglycaemia responsive to sulfonylurea
    • Abstract: Publication date: September 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 4
      Author(s): M.S.E. Ebrahim , M.L. Lawson , M.T. Geraghty
      Aim To describe the atypical phenotype and genotype of an adolescent girl with symptomatic exercise-induced hyperglycaemia, responsive to sulfonylurea treatment. Methods Chart review, gene sequencing, and blinded continuous glucose monitoring (Medtronic iPro2) were used to characterise the case. Results A novel heterozygous mutation p.Q219x (c.655C>T) in exon 6 of the glucokinase gene (NM_000162.3) was confirmed in the patient and father. Initiation of gliclazide 20mg twice daily was associated with resolution of symptoms and normalization of haemoglobin A1C (5.6%). Blinded continuous glucose monitoring demonstrated significantly less time spent in the hyperglycaemic range (sensor glucose>8.0mmol/L) when on twice daily gliclazide versus intermittent or no gliclazide (mean minutes/day with sensor glucose>8mmol/L: 53.6±90.0 vs. 307.9±246.6; P =0.04). Conclusions This novel mutation in the glucokinase gene led to atypical symptomatic exercise-induced hyperglycaemia that was responsive to low dose sulfonylurea with self-reported additional benefit after reduction of carbohydrate intake. We postulate that her atypical clinical presentation was related to the intense elite-level physical activity combined with carbohydrate loading before exercise.


      PubDate: 2014-09-17T23:57:58Z
       
  • Early changes in respiratory quotient and resting energy expenditure
           predict later weight changes in patients treated for poorly controlled
           type 2 diabetes
    • Abstract: Publication date: September 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 4
      Author(s): C. Gonzalez , C. Fagour , E. Maury , B. Cherifi , S. Salandini , A. Pierreisnard , P. Masquefa-Giraud , H. Gin , V. Rigalleau
      Aim This study looked at whether early changes in resting energy expenditure (REE) and respiratory quotient (RQ) are correlated with later weight changes in patients with type 2 diabetes (T2D) being treated with insulin or GLP-1 analogues, or diet. Methods A total of 67 patients (age: 57±9 years; BMI: 33.7±5.0kg/m2; HbA1c: 9.9±1.5%) began taking an insulin analogue at bedtime (INS, n =28; initial dose: 0.2 IU/kg) or a GLP-1 analogue (GLP-1, n =23), or only a dietary intervention (diet, n =16; restricted carbohydrates and calories). Their respiratory exchanges were monitored on days 0, 1 and 2 before breakfast. Results Two days after starting the bedtime insulin analogue, fasting glycaemia improved (INS: −65±41mg/dL; GLP-1: −29±48mg/dL; diet: −31±46mg/dL; P <0.05), REE decreased (INS: −162±241kcal/24h; GLP-1: 0±141kcal/24h; diet: −41±154kcal/24h; P <0.05) and RQ increased (from 0.76±0.04 to 0.80±0.04; P <0.01), whereas only RQ decreased with diet (from 0.79±0.05 to 0.76±0.04; P <0.05) and remained unchanged with GLP-1 (P <0.005 for ΔRQ across treatments). Only 33 patients attended the scheduled examination three months later. HbA1c improved (INS, n =16: −1.7±1.4%; GLP-1, n =12: −2.1±1.4%; diet, n =5: −1.7±2.8%; NS), while weight changes differed (INS: +1.5±4.3kg; GLP-1: −2.8±2.8kg; diet: −2.2±2.7kg; P <0.005). After three months, weight changes correlated with early changes in REE (r=−0.37, P <0.05) and RQ (r=+0.43, P <0.01), and remained correlated when both changes were included in a multivariate regression analysis (r=0.58, P <0.005). Conclusion In poorly controlled patients with T2D and two days after the introduction of a bedtime insulin analogue, REE decreased by −9% while RQ increased by +5%, pointing to a reduction of lipid oxidation. These changes were predictive of later weight gain.


      PubDate: 2014-09-17T23:57:58Z
       
  • Effects of alcohol consumption and the metabolic syndrome on 10-year
           incidence of diabetes: The ATTICA study
    • Abstract: Publication date: Available online 2 September 2014
      Source:Diabetes & Metabolism
      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: 2014-09-03T21:36:11Z
       
  • Anthropometric markers for detection of the metabolic syndrome in
           adolescents
    • Abstract: Publication date: Available online 6 August 2014
      Source:Diabetes & Metabolism
      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: 2014-08-09T20:40:02Z
       
  • Isoprostane as oxidative stress biomarker in the VARIAFIT study:
           Analytical and methodological considerations
    • Abstract: Publication date: Available online 30 June 2014
      Source:Diabetes & Metabolism
      Author(s): D. Monneret



      PubDate: 2014-07-28T19:33:53Z
       
  • Adiponectin is expressed in the pancreas of high-fat-diet-fed mice and
           protects pancreatic endothelial function during the development of type 2
           diabetes
    • Abstract: Publication date: Available online 27 June 2014
      Source:Diabetes & Metabolism
      Author(s): X.-X. Liu , K.-Y. Liu , P. Li , S. Han , X.-D. Peng , L. Shen
      Aim Adiponectin levels in skeletal muscle and adipose tissue have been reported to be involved in insulin resistance in rats fed with a high-fat diet (HFD). Our objective was to explore whether adiponectin is also expressed in the pancreas and what its potential role is during the development of type 2 diabetes (T2D) in outbred CD-1 mice. Methods Male 4-week-old outbred CD-1 mice were fed an HFD to induce a polygenic model of human T2D. Adiponectin expression was examined in mouse pancreas by quantitative real-time polymerase chain reaction (qPCR), western blots and immunofluorescence analyses. Human umbilical vein endothelium cells (HUVECs) were transfected with an adiponectin-expressing lentivirus to determine the effect of adiponectin on angiogenic function in vitro. Results Feeding mice an HFD for 9weeks resulted in constant hyperglycaemia, obesity, impaired glucose tolerance and insulin resistance. Additional hyperinsulinaemia emerged in mice fed an HFD for 18weeks. Interestingly, aberrant expression of adiponectin was detectable in the pancreatic vascular endothelial cells (VECs) of mice fed with an HFD, but not in mice fed with regular chow (RC). Expression levels of pancreatic adiponectin varied during the development of T2D. This extraordinary expression of adiponectin in pancreatic VECs played a role in protecting endothelial function against potential damage by HFD. Our in vitro study has demonstrated that adiponectin promotes angiogenic function. Conclusion These results reveal for the first time that adiponectin is expressed in pancreatic VECs of HFD-fed mice during the development of T2D as a protective adaptation in response to the HFD.


      PubDate: 2014-07-28T19:33:53Z
       
  • Anaemia, a common but often unrecognized risk in diabetic patients: A
           review
    • Abstract: Publication date: Available online 17 July 2014
      Source:Diabetes & Metabolism
      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: 2014-07-28T19:33:53Z
       
  • Retrospective cohort study evaluating exenatide twice daily and
           long-acting insulin analogs in a Veterans Health Administration population
           with type 2 diabetes
    • Abstract: Publication date: Available online 22 July 2014
      Source:Diabetes & Metabolism
      Author(s): M. Bounthavong , J.N. Tran , S. Golshan , N.F. Piland , C.M. Morello , A. Blickensderfer , J.H. Best
      Aim This was a retrospective cohort study that evaluated the differences in glycated haemoglobin (HbA1c) and body mass index (BMI) in veterans with type 2 diabetes mellitus (T2DM), prescribed exenatide twice daily (BID) versus long-acting insulin analog (LAIA) two years after initiation in the United States (US) veteran population. Materials and methods Patients were included if they were≥18 years old with T2DM, and initiated exenatide BID or LAIA at the Veterans Health Administration between January 1, 2006 and December 31, 2010. Multivariate models were used to evaluate the changes in HbA1c and BMI between groups, controlling for potential confounders. Logistic regression was used to evaluate the odds of achieving≥0.5% HbA1c reduction based on baseline HbA1c stratifications: low,<7%; moderate, 7% to<9%; and high,≥9%. Results A total of 446 exenatide BID and 51,531 LAIA patients met inclusion/exclusion criteria. On average, exenatide BID patients were significantly older (64 versus 60 years) with a higher BMI (37.8 versus 32.9kg/m2). Baseline HbA1c was 8.2% and 8.8% for exenatide BID and LAIA patients, respectively (P <0.001); otherwise, patients were similar for all other characteristics. Exenatide BID treatment was significantly associated with a 0.32% (95%CI: 0.18–0.47%) greater reduction in HbA1c at two years compared with LAIA. Similar findings were observed for BMI reduction (0.68kg/m2; 95%CI: 0.42–0.95kg/m2). Exenatide BID patients with moderate baseline HbA1c had significantly higher odds of achieving≥0.5% HbA1c reduction compared with LAIA patients (OR=1.5; 95%CI: 1.2–2.0). Conclusions Veterans treated with exenatide BID had significantly greater reduction in HbA1c and BMI compared with patients treated with LAIA patients two years after initiation.


      PubDate: 2014-07-28T19:33:53Z
       
  • LMNA gene mutation as a model of cardiometabolic dysfunction: From genetic
           analysis to treatment response
    • Abstract: Publication date: June 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 3
      Author(s): V. Chirico , V. Ferraù , I. Loddo , S. Briuglia , M. Amorini , V. Salpietro , A. Lacquaniti , C. Salpietro , T. Arrigo
      Aim This report highlights the metabolic, endocrine and cardiovascular comorbidities in a case of familial partial lipodystrophy (FPLD), and also evaluates the efficacy and safety of metformin therapy. Methods Mutational analysis was carried out of the LMNA gene in a teenage girl with an FPLD phenotype. Insulin resistance, sex hormones and metabolic parameters were also evaluated, and echocardiography, electrocardiography and 24-h blood pressure monitoring were also done. Results The patient showed atypical fat distribution, insulin resistance and hypertrophic cardiomyopathy. Physical examination revealed muscle hypertrophy with a paucity of fat in the extremities, trunk and gluteal regions, yet excess fat deposits in the face, neck and dorsal cervical region. LMNA sequencing revealed a heterozygous missense mutation (c.1543A>G) in exon 9, leading to substitution of lysine by glutamic acid at position 515 (K515E). Moderate hypertension and secondary polycystic ovary syndrome were also assessed. Treatment with metformin resulted in progressive improvement of metabolic status, while blood pressure values normalized with atenolol therapy. Conclusions Very rapid and good results with no side-effects were achieved with metformin therapy for FPLD. The association of an unusual mutation in the LMNA gene was also described.


      PubDate: 2014-06-27T16:48:13Z
       
  • Metformin accumulation without hyperlactataemia and metformin-induced
           hyperlactataemia without metformin accumulation
    • Abstract: Publication date: June 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 3
      Author(s): J.D. Lalau , M.L. Azzoug , F. Kajbaf , C. Briet , R. Desailloud
      Aim These case reports demonstrate that, at the individual level, blood metformin concentrations and metformin effects on lactate do not always correlate. Methods We report here on two unusual cases: metformin accumulation in the absence of hyperlactataemia; and metformin-induced hyperlactataemia with no metformin accumulation. Results Patient #1 presented with severe kidney failure, severe acidosis (pH: 7.04), normal lactataemia (0.90mmol/L) and marked metformin accumulation. Patient #2 presented with hyperlactataemia, even after dose reduction, during otherwise well-tolerated metformin treatment. Arterial lactate levels were 8.8, 8.2 and 4.7mmol/L during metformin therapy with daily doses of 2550, 1700 and 850mg, respectively. After withdrawal, metformin was reintroduced for 5-day periods at 500mg/day up to 2000mg/day with washout intervals. Lactate concentration, normal at baseline, rapidly exceeded 2mmol/L after metformin administration. Conclusion These clinical data suggest a new concept for metformin therapy: there may be either resistance or, conversely, hypersensitivity to metformin effects on lactate generation according to the individual patient.


      PubDate: 2014-06-27T16:48:13Z
       
  • Body weight, weight gain and hyperglycaemia are associated with
           hypertensive disorders of pregnancy in women with gestational diabetes
    • Abstract: Publication date: June 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 3
      Author(s): B. Barquiel , L. Herranz , C. Grande , I. Castro-Dufourny , M. Llaro , P. Parra , M.A. Burgos , L.F. Pallardo
      Aim The aim of this study was to measure the capacity of glucose- and weight-related parameters to predict pregnancy-induced hypertensive disorders in women with gestational diabetes. Methods An observational study was conducted involving 2037 women with gestational diabetes. The associations of glycaemic and weight-related parameters with pregnancy-induced hypertensive disorders were obtained by univariate and adjusted multivariate analyses. Also, model predictability and attributable predictor risk percentages were calculated, and collinearity and factor interactions examined. Results Multivariate analyses revealed that hypertensive disorders were mainly predicted by average third-trimester glycated haemoglobin (HbA1c) levels≥5.9%, by being overweight or obese before pregnancy and by excess gestational weight gain after adjusting for age, tobacco use, chronic hypertension, parity, urinary tract infections and gestational age at delivery. Prepregnancy body weight (overweight and obesity) had the strongest impact on pregnancy-related hypertensive disorders (attributable risk percentages were 51.5% and 88.8%, respectively). The effect of being overweight or obese on hypertensive disorders was enhanced by HbA1c levels and gestational weight gain, with elevated HbA1c levels multiplying the effect of being overweight before pregnancy. Conclusion The average third-trimester HbA1c level is a novel risk factor for pregnancy-induced hypertensive disorders in women with gestational diabetes. HbA1c levels≥5.9%, prepregnancy overweight or obesity and excess gestational weight gain are all independent risk factors of pregnancy-related hypertensive disorders in such women. In treated gestational diabetes patients, the strongest influence on hypertensive disorders is prepregnancy obesity.


      PubDate: 2014-06-27T16:48:13Z
       
  • Baseline osteocalcin levels and incident diabetes in a 3-year prospective
           study of high-risk individuals
    • Abstract: Publication date: June 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 3
      Author(s): S. Liatis , P.P. Sfikakis , A. Tsiakou , C. Stathi , E. Terpos , N. Katsilambros , K. Makrilakis
      Aim Experimental evidence suggests that osteocalcin is a key messenger that affects both adipocytes and insulin-producing β cells. Epidemiological cross-sectional studies have shown a negative association between plasma levels of osteocalcin and glucose. For this reason, the hypothesis that lower baseline osteocalcin plasma levels are associated with diabetes was prospectively tested. Methods The study population consisted of individuals at high risk for type 2 diabetes who were screened for participation in the Greek arm of a European type 2 diabetes prevention study (the DE-PLAN study). All participants were free of diabetes at baseline and underwent a second evaluation 3 years later. Diabetes status was defined according to an oral glucose tolerance test. Results A total of 307 subjects were included in the present analysis. The population, including 154 men (50.3%), was middle-aged (54.4±10.2 years) and overweight (BMI: 29.5±4.9kg/m2). At baseline, mean total plasma osteocalcin was lower in those with impaired fasting glucose and/or impaired glucose tolerance compared with those with normal glucose tolerance (6.0±3.1ng/mL vs. 7.3±4.0ng/mL, respectively; P =0.01). After 3 years, 36 subjects had developed diabetes. In the prospective evaluation, there was no association between baseline osteocalcin levels and diabetes (OR: 1.04 per 1ng/mL, 95% CI: 0.93–1.15; P =0.49) on multivariable logistic regression analysis, nor was there any correlation with changes in plasma glucose after 3 years (r=0.09, P =0.38). Conclusion Our prospective results show that lower levels of circulating osteocalcin do not predict future diabetes development and, in contrast to most cross-sectional published data so far, suggest that this molecule may not be playing a major role in glucose homoeostasis in humans.


      PubDate: 2014-06-27T16:48:13Z
       
  • Central orchestration of peripheral nutrient partitioning and substrate
           utilization: Implications for the metabolic syndrome
    • Abstract: Publication date: June 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 3
      Author(s): R.G.P. Denis , A. Joly-Amado , C. Cansell , J. Castel , S. Martinez , A.S. Delbes , S. Luquet
      Energy homoeostasis is maintained through a complex interplay of nutrient intake and energy expenditure. The central nervous system is an essential component of this regulation, as it integrates circulating signals of hunger and satiety to develop adaptive responses at the behavioural and metabolic levels, while the hypothalamus is regarded as a particularly crucial structure in the brain in terms of energy homoeostasis. The arcuate nucleus (ARC) of the hypothalamus contains at least two intermingled neuronal populations: the neurons that produce neuropeptide Y (NPY); and the Agouti-related protein (AgRP) produced by AgRP/NPY neurons situated below the third ventricle in close proximity to proopiomelanocortin (POMC)-producing neurons. POMC neurons exert their catabolic and anorectic actions by releasing α-melanocyte-stimulating hormone (α-MSH), while AgRP neurons oppose this action by exerting tonic GABAergic inhibition of POMC neurons and releasing the melanocortin receptor inverse agonist AgRP. The release of neurotransmitters and neuropeptides by second-order AgRP neurons appears to take place on a multiple time scale, thereby allowing neuromodulation of preganglionic neuronal activity and subsequent control of nutrient partitioning – in other words, the coordinated regulation of conversion, storage and utilization of carbohydrates vs. lipids. This suggests that the function of AgRP neurons extends beyond the strict regulation of feeding to the regulation of efferent organ activity, such that AgRP neurons may now be viewed as an important bridge between central detection of nutrient availability and peripheral nutrient partitioning, thus providing a mechanistic link between obesity and obesity-related disorders.


      PubDate: 2014-06-27T16:48:13Z
       
  • Managing the manager: Gut microbes, stem cells and metabolism
    • Abstract: Publication date: June 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 3
      Author(s): M. Serino , V. Blasco-Baque , S. Nicolas , R. Burcelin
      One major discovery of the last decade in the field of metabolic diseases is that the microorganisms comprising the gut microbiota are now considered a metabolic “organ”, modulating multiple functions of the host, such as intestinal immune system maturation, adiposity, cardiac metabolism, liver triglyceride storage, and brain development and behaviour. The corresponding mechanisms involve increased energy harvesting through the production by microbiota of short-chain fatty acids for use by the host, and the release of pro-inflammatory compounds, such as lipopolysaccharide (LPS), flagellin and peptidoglycan. In particular, a high-fat diet (HFD) modifies gut microbiota, resulting in an increase of plasma LPS levels known as “metabolic endotoxaemia”, a major driver of the onset of metabolic diseases through a CD14-dependent mechanism. The LPS-sensitive cell types can be seen within bone marrow-derived cells (BMC), which are involved in the development of inflammation in the adipose tissue of obese and type 2 diabetic mice. Furthermore, the expression of LPS receptor/cofactor CD14 cells from the stromal vascular fraction of adipose depots can also be directly targeted by LPS to initiate precursor cell development and adiposity. Moreover, data from the literature also indicate an impact of gut microbiota on intestinal stem cells. Thus, this mini review presents the experimental evidence supporting a relationship between gut microbiota and stem cells as a new axis of metabolic homoeostasis control.


      PubDate: 2014-06-27T16:48:13Z
       
  • Effects of pharmacological treatments on micro- and macrovascular
           complications of type 2 diabetes: What is the level of evidence'
    • Abstract: Publication date: June 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 3
      Author(s): R. Boussageon , F. Gueyffier , C. Cornu
      Antidiabetic drugs for type 2 diabetes receive marketing authorization if they show efficacy in reducing levels of HbA1c. However, efficacy on this biological criterion does not necessarily reflect clinical benefit to patients. Several randomized clinical trials have shown that antidiabetic drugs reduce HbA1c without a corresponding reduction in clinical events. This suggests a need to focus on the clinical effectiveness (morbimortality criteria) of our available antidiabetic drugs. In this non-extensive review of the literature, it was found that none of the current antidiabetic drugs have clearly proven their superiority over placebo in the gold standard double-blind randomized clinical trials. Thus, in 2013, the level of evidence for the clinical efficacy of antidiabetic drugs is disappointing and does not support the millions of prescriptions being written for them.


      PubDate: 2014-06-27T16:48:13Z
       
  • Editorial Board
    • Abstract: Publication date: June 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 3




      PubDate: 2014-06-27T16:48:13Z
       
  • Regulation of growth hormone induced JAK2 and mTOR signalling by hepatic
           protein tyrosine phosphatase 1B
    • Abstract: Publication date: Available online 16 June 2014
      Source:Diabetes & Metabolism
      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: 2014-06-27T16:48:13Z
       
  • Maternal diabetes, programming of beta-cell disorders and
           intergenerational risk of type 2 diabetes
    • Abstract: Publication date: Available online 16 June 2014
      Source:Diabetes & Metabolism
      Author(s): A. Chavey , M.-D. Ah Kioon , D. Bailbé , J. Movassat , B. Portha
      A substantial body of evidence suggests that an abnormal intra-uterine milieu elicited by maternal metabolic disturbances as diverse as malnutrition, placental insufficiency, diabetes and obesity may be able to programme susceptibility of the foetus to later develop chronic degenerative diseases such as obesity, hypertension, cardiovascular diseases and type 2 diabetes (T2D). As insulin-producing cells have been placed centre stage in the development of T2D, this review examines developmental programming of the beta-cell mass (BCM) in various rodent models of maternal protein restriction, calorie restriction, overnutrition and diabetes. The main message is that whatever the initial maternal insult (F0 generation) and whether alone or in combination, it gives rise to the same programmed BCM outcome in the daughter generation (F1). The altered BCM phenotype in F1 females prohibits normal BCM adaptation during pregnancy and, thus, diabetes (gestational diabetes) ensues. This gestational diabetes is then passed from one generation (F1) to the next (F2, F3 and so on). This review highlights a number of studies that have identified epigenetic mechanisms that may contribute to altered BCM development and beta-cell failure, as observed in diabetes. In addition to their role in instilling the programmed defect, these non-genomic mechanisms may also be involved in its intergenerational transmission.


      PubDate: 2014-06-27T16:48:13Z
       
  • 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
       
  • Serum bilirubin as a predictor of incident metabolic syndrome: A 4-year
           retrospective longitudinal study of 6205 initially healthy Korean men
    • Abstract: Publication date: Available online 18 June 2014
      Source:Diabetes & Metabolism
      Author(s): M.J. Lee , C.H. Jung , Y.M. Kang , J.Y. Hwang , J.E. Jang , J. Leem , J.-Y. Park , H.-K. Kim , W.J. Lee
      Aim Serum bilirubin is an endogenous antioxidant with anti-inflammatory properties. Several cross-sectional studies have reported that bilirubin was negatively associated with oxidative stress-mediated diseases, including the metabolic syndrome (MetS). However, the clinical relevance of bilirubin as a risk factor for incident MetS remains controversial. For this reason, the longitudinal effects of baseline serum bilirubin concentrations on incident MetS were evaluated in Korean men. Methods This 4-year retrospective longitudinal observational study involved 6205 Korean men without MetS. Subjects underwent routine health examinations in 2007 and returned for a follow-up examination in 2011. Baseline serum bilirubin concentrations were determined using the vanadate oxidation method. Results During the 4-year period, 936 cases of incident MetS (15.1%) were identified. Its incidence decreased across baseline bilirubin quartile categories (P <0.001), with an odds ratio (OR) for developing MetS being significantly lower in the highest quartile group (≥1.40mg/dL) compared with the lowest (≤0.90mg/dL) after adjusting for all confounding variables [OR=0.70, 95% confidence interval (CI) 0.54–0.90; P for trend=0.019]. Among individual components of MetS, bilirubin was found to be negatively associated with only the risk of incident hypertriglyceridaemia. The OR (95% CI) for incident hypertriglyceridaemia in the highest vs lowest quartile was 0.75 (0.61–0.91; P for trend=0.002). Conclusion Serum total bilirubin level was negatively associated with incidence of MetS in healthy Korean men over a 4-year period.


      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
       
  • Associations between the common HNF1A gene variant p.I27L (rs1169288) and
           risk of type 2 diabetes mellitus are influenced by weight
    • Abstract: Publication date: Available online 2 June 2014
      Source:Diabetes & Metabolism
      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: 2014-06-07T14:49:20Z
       
  • Anti-sRAGE autoimmunity in obesity: Downturn after bariatric surgery is
           independent of previous diabetic status
    • Abstract: Publication date: Available online 2 June 2014
      Source:Diabetes & Metabolism
      Author(s): R. Lorenzi , F. Pattou , J.-B. Beuscart , N. Grossin , M. Lambert , P. Fontaine , R. Caiazzo , M. Pigeyre , A. Patrice , M. Daroux , E. Boulanger , S. Dubucquoi
      Aim Morbid obesity increases the risk of cardiovascular disease (CVD). The receptor for advanced glycation end-products (RAGE) is implicated in proinflammatory processes that underlie CVD. Its soluble form (sRAGE) has been proposed as a vascular biomarker. Recently, anti-sRAGE autoantibodies were described and found to be increased in diseases where RAGE is overexpressed. This study aimed to investigate serum levels of anti-sRAGE autoantibodies in morbidly obese patients. Methods After exclusion based on specific criteria, 150 subjects (50 normoglycemics, 50 glucose-intolerants and 50 diabetics) were randomly recruited from a cohort of 750 obese patients (ABOS). Serum sRAGE and anti-sRAGE autoantibodies were measured before bariatric surgery. Sixty-nine patients were followed for up to 1year after gastric bypass, and their levels of sRAGE and anti-sRAGE autoantibodies measured. The control group consisted of healthy blood donors. Results Compared with controls, baseline levels of sRAGE and anti-sRAGE autoantibodies were significantly higher in all obese patients independently of glucose regulation (P <0.001). At 1year after gastric bypass, sRAGE and anti-sRAGE were decreased (P <0.001). The decrease in anti-sRAGE autoantibodies was correlated with an increase in high-density lipoprotein (HDL; P =0.02). Conclusion Independently of previous diabetic status, morbid obesity increases sRAGE and anti-sRAGE levels. Weight loss after gastric bypass is followed by a decrease in both titres. The decrease in anti-sRAGE correlates with an increase in HDL.


      PubDate: 2014-06-07T14:49:20Z
       
  • 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
       
  • Erratum to “The impact of anxiety and depression on patients within
           a large type 1 diabetes insulin pump population. An observational
           study” [Diabetes Metab. 29 (2013) 439–44]
    • Abstract: Publication date: Available online 28 May 2014
      Source:Diabetes & Metabolism
      Author(s): P. Grant , D. Dworakowska , N. DeZoysa , D. Barnes



      PubDate: 2014-06-01T14:24:10Z
       
  • Prevalence of anxiety and depression among diabetic African patients in
           Guinea: Association with HbA1c levels
    • Abstract: Publication date: Available online 28 May 2014
      Source:Diabetes & Metabolism
      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: 2014-06-01T14:24:10Z
       
  • Erratum to “Telemedicine and type 1 diabetes: Is technology per se
           sufficient to improve glycaemic control'” [Diabetes Metab. 40
           (2014) 61–6]
    • Abstract: Publication date: Available online 27 May 2014
      Source:Diabetes & Metabolism
      Author(s): S. Franc , S. Borot , O. Ronsin , J.-L. Quesada , D. Dardari , C. Fagour , E. Renard , A.-M. Leguerrier , C. Vigeral , F. Moreau , P. Winiszewski , A. Vambergue , H. Mosnier-Pudar , L. Kessler , S. Reffet , B. Guerci , L. Millot , S. Halimi , C. Thivolet , P.-Y. Benhamou , A. Penfornis , G. Charpentier , H. Hanaire



      PubDate: 2014-06-01T14:24:10Z
       
  • Prevalence of diabetes and depressive symptomatology and their effect on
           mortality risk in elderly Italians: The Italian Longitudinal Study on
           Aging
    • Abstract: Publication date: Available online 28 May 2014
      Source:Diabetes & Metabolism
      Author(s): F. Limongi , M. Noale , G. Crepaldi , S. Maggi
      Aim This study assessed the prevalence of depressive symptomatology (DS) in older individuals with diabetes to determine whether diabetes and DS are independent predictors of mortality, and if their coexistence is associated with an increased mortality risk. Methods Analyses were based on data from the Italian Longitudinal Study on Aging (ILSA), a prospective community-based cohort study in which 5632 individuals aged 65–84years were enrolled. The role of diabetes and DS in all-cause mortality was evaluated using the Cox model, adjusted for possible confounders, for four groups: 1) those with neither diabetes nor DS (reference group); 2) those with DS but without diabetes; 3) those with diabetes but no DS; and 4) those with both diabetes and DS. Results Type 2 diabetes mellitus (T2DM) was present in 13.8% of the participants; they presented with higher baseline rates of DS compared with the non-diabetic controls. During the first follow-up period, participants with DS but not diabetes had a 42% higher risk of all-cause mortality compared with the reference control group (HR=1.42; 95% CI: 1.02–1.96), while participants with diabetes but not DS had an 83% higher risk of death than the reference group (HR=1.83; 95% CI: 1.19–2.80). The risk of death for those with both disorders was more than twice that for the reference group (HR=2.58; 95% CI: 1.55–4.29). Analyses of deaths from baseline to the second follow-up substantially confirmed these results. Conclusion The prevalence rate of DS is higher in elderly people with diabetes and their coexistence is associated with an increased mortality risk.


      PubDate: 2014-06-01T14:24:10Z
       
  • Glycaemic variability and ambient hyperglycaemia: How and when are they
           linked'
    • Abstract: Publication date: Available online 19 May 2014
      Source:Diabetes & Metabolism
      Author(s): L. Monnier , C. Colette



      PubDate: 2014-05-25T16:16:38Z
       
  • 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
       
  • Longitudinal left ventricular strain impairment in type 1 diabetes
           children and adolescents: A 2D speckle strain imaging study
    • Abstract: Publication date: Available online 9 May 2014
      Source:Diabetes & Metabolism
      Author(s): F. Labombarda , M. Leport , R. Morello , V. Ribault , D. Kauffman , J. Brouard , A. Pellissier , P. Maragnes , A. Manrique , P. Milliez , E. Saloux
      Aim Type 1 diabetes (T1D) involves complex metabolic disturbances in cardiomyocytes leading to morphological and functional abnormalities of the myocardium. The relationship between T1D and cardiac structure and function in children is not well established. Our study investigated whether T1D is associated with early subclinical myocardial disturbances in children and adolescents, and whether the state of metabolic control and diabetes duration are influential factors. Methods Standard echocardiography, tissue Doppler imaging (TDI) and two-dimensional (2D) strain imaging were prospectively performed in 100 T1D children (age: 11.3±3.6years, 52 boys) and compared with 79 controls. Results The diabetic and control children were comparable with respect to age, gender, heart rate and blood pressure. There were no significant differences between the two groups in left ventricular (LV) ejection fraction, LV remodelling and TDI parameters. Conventional mitral Doppler demonstrated significantly fewer diastolic filling abnormalities with an early filling wave in the diabetes group. Global longitudinal strain (GLS) was also significantly lower in the T1D children, while circumferential strain and radial strain did not differ. GLS correlated with HbA1c (r =0.52; P <0.01), but there was no correlation with diabetes duration. Conclusion Our results suggest that LV longitudinal myocardial deformation is decreased in young patients with T1D, and glycaemic control may be the main risk factor for these changes. Further follow-up is now necessary to precisely determine the clinical significance of these myocardial changes detected by 2D strain imaging in T1D children.


      PubDate: 2014-05-10T06:28:54Z
       
  • Differences in vitamin D concentration between metabolically healthy and
           unhealthy obese adults: Associations with inflammatory and cardiometabolic
           markers in 4391 subjects
    • Abstract: Publication date: Available online 5 May 2014
      Source:Diabetes & Metabolism
      Author(s): A. Esteghamati , Z. Aryan , A. Esteghamati , M. Nakhjavani
      Aim This study aimed to compare concentrations of serum 25-hydroxy vitamin D and inflammatory markers in metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), and to determine whether the relationship between vitamin D levels and both cardiometabolic and inflammatory markers differs between MHO and MUO. Methods This cross-sectional study comprised 4391 obese subjects aged>18 years. A panel of cardiometabolic and inflammatory markers, including anthropometric variables, glycaemic indices, lipid profiles, liver enzymes, homocysteine, C-reactive protein (CRP), fibrinogen and serum 25-hydroxy vitamin D levels, was investigated. All cardiometabolic and inflammatory markers in MHO and MUO as well as in vitamin D deficiency were compared. Results Prevalence of MHO was 41.9% in our obese subjects using International Diabetes Federation criteria. Considering insulin resistance and inflammation, the prevalence of MHO was 38.4%. Individuals with MHO had significantly higher vitamin D concentrations compared with MUO, and this difference in vitamin D status persisted after accounting for BMI and waist circumference. Subjects with MHO had significantly better metabolic status, lower liver enzymes, lower inflammatory markers and higher serum 25-hydroxy vitamin D than those with MUO. Associations between vitamin D levels and inflammatory and cardiometabolic markers differed according to MHO/MUO status. Among MUO subjects, vitamin D deficiency was associated with higher liver marker and homocysteine levels. Serum vitamin D was negatively associated with fasting plasma glucose and HbA1c in MHO only. Conclusion Serum 25-hydroxy vitamin D levels were lower in MUO vs MHO, and reduced vitamin D concentrations were more strongly associated with cardiometabolic and inflammatory markers in MUO than in MHO subjects. These findings suggest that a deficiency in vitamin D could be a key component of MUO.


      PubDate: 2014-05-10T06:28:54Z
       
  • 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
       
  • Effects of glucose-lowering agents on vascular outcomes in type 2
           diabetes: A critical reappraisal
    • Abstract: Publication date: Available online 30 April 2014
      Source:Diabetes & Metabolism
      Author(s): A.J. Scheen , B. Charbonnel
      Type 2 diabetes mellitus (T2DM) is strongly associated with cardiovascular complications, especially coronary artery disease. Numerous epidemiological studies have shown a close relationship between major cardiovascular events and glycaemia, and several pathophysiological mechanisms have been described that explain how hyperglycaemia induces vascular damage. However, randomized controlled trials investigating either an intensive glucose-lowering strategy vs standard care or the addition of a new glucose-lowering agent vs a placebo have largely failed to demonstrate any clinical benefits in terms of cardiovascular morbidity or mortality. This lack of evidence has led some people to contest the clinical efficacy of lowering blood glucose in patients with T2DM, despite its positive effects on microvascular complications. This article analyzes the various reasons that might explain such discrepancies. There are still strong arguments in favour of targeting hyperglycaemia while avoiding other counterproductive effects, such as hypoglycaemia and weight gain, and of integrating the glucose-lowering approach within a global multi-risk strategy to reduce the burden of cardiovascular disease in T2DM.


      PubDate: 2014-05-05T11:18:02Z
       
  • Polymerase chain reaction–denaturing gradient gel electrophoresis
           (PCR–DGGE): A promising tool to diagnose bacterial infections in
           diabetic foot ulcers
    • Abstract: Publication date: Available online 21 April 2014
      Source:Diabetes & Metabolism
      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: 2014-04-25T11:16:16Z
       
  • Ethnic differences in the relationship between birth weight and type 2
           diabetes mellitus in postmenopausal women
    • Abstract: Publication date: Available online 21 April 2014
      Source:Diabetes & Metabolism
      Author(s): K.K. Ryckman , E. Rillamas-Sun , C.N. Spracklen , R.B. Wallace , L. Garcia , F.A. Tylavsky , B.V. Howard , S. Liu , Y. Song , E.S. LeBlanc , M.V. White , N.I. Parikh , J.G. Robinson
      Aim The objective of this study is to examine the relationship between self-reported birth weight and the adult occurrence of type 2 diabetes mellitus in a large multi-ethnic population of women. Methods Baseline data from the Women's Health Initiative Observational Study [n =75,993] was used to examine the association between participant birth weight category and prevalent type 2 diabetes mellitus. Models were adjusted for age, ethnicity, body mass index and other pertinent risk factors. Sub-analyses were performed stratifying by ethnicity. Results There was a strong inverse association between birth weight and type 2 diabetes mellitus with a birth weight of <6 pounds (lbs) (OR: 1.16, 95% CI: 1.01, 1.33) significantly associated with an increased risk of type 2 diabetes mellitus and a birth weight of ≥10 lbs (OR: 0.72, 95% CI: 0.57, 0.92) associated with a decreased risk of type 2 diabetes mellitus compared to women who reported their birth weight between 7 and 8 lbs 15 ounces (oz). Stratifying by ethnicity, the inverse association between birth weight and type 2 diabetes mellitus was only apparent in White women, but not Black, Hispanic or Asian women. Conclusion Lower birth weight was associated with increased T2D risk in American White and Black post-menopausal women.


      PubDate: 2014-04-25T11:16:16Z
       
  • Editorial Board
    • Abstract: Publication date: April 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 2




      PubDate: 2014-04-20T06:45:12Z
       
  • Do not forget that type 2 diabetes does not only expose to cardiovascular
           complications
    • Abstract: Publication date: Available online 18 April 2014
      Source:Diabetes & Metabolism
      Author(s): S. Halimi



      PubDate: 2014-04-20T06:45:12Z
       
  • Characterization of metabolically healthy but obese individuals: Should we
           add vitamin D to the puzzle'
    • Abstract: Publication date: Available online 16 April 2014
      Source:Diabetes & Metabolism
      Author(s): A.D. Karelis , R. Rabasa-Lhoret



      PubDate: 2014-04-20T06:45:12Z
       
  • Update on cognitive decline and dementia in elderly patients with diabetes
    • Abstract: Publication date: Available online 2 April 2014
      Source:Diabetes & Metabolism
      Author(s): L. Bordier , J. Doucet , J. Boudet , B. Bauduceau
      Aim This article is an update of the relationship between type 2 diabetes (T2D), cognitive dysfunction and dementia in older people. Methods and results The number of older patients consulting for diabetes who also exhibit cognitive difficulties is consistently growing because of the increased longevity of the population as a whole and, according to a number of studies, the increased risk of cognitive impairment and dementia in older diabetic patients. Many studies have demonstrated a link between poor glucose control and deteriorated cognitive function in diabetic patients. A history of severe hypoglycaemic episodes has also been associated with a greater risk of late-in-life cognitive deficits and dementia in patients with T2D. Several processes are thought to promote cognitive decline and dementia in diabetics. Based on both clinical and non-clinical findings, the factors most likely to alter brain function and structure are cerebrovascular complications of diabetes, alterations in glucose and insulin, and recurrent hypoglycaemia. Together with other diabetes complications, cognitive deficits contribute to functional impairment, increased frequency of depression-related symptoms, greater incidence of recurrent hypoglycaemia, poorer adherence to treatment and, finally, poorer prognosis, as evidenced by recent longitudinal studies. Conclusion Clinical guidelines have recently been devised for older diabetic patients, particularly those with cognitive deficits and a reduced capacity to self-manage. In the most vulnerable patients, specific treatment strategies have been proposed for glycaemic control to limit metabolic decompensation and avoid the risk of hypoglycaemia. Educational measures, provided mainly to maintain patient autonomy and avoid hospital admission, have also been adapted according to patients’ cognitive and functional status.


      PubDate: 2014-04-05T01:42:05Z
       
  • Effects of adipose tissue distribution on maximum lipid oxidation rate
           during exercise in normal-weight women
    • Abstract: Publication date: Available online 31 March 2014
      Source:Diabetes & Metabolism
      Author(s): L. Isacco , D. Thivel , M. Duclos , J. Aucouturier , N. Boisseau
      Aim Fat mass localization affects lipid metabolism differently at rest and during exercise in overweight and normal-weight subjects. The aim of this study was to investigate the impact of a low vs high ratio of abdominal to lower-body fat mass (index of adipose tissue distribution) on the exercise intensity (Lipoxmax) that elicits the maximum lipid oxidation rate in normal-weight women. Methods Twenty-one normal-weight women (22.0±0.6 years, 22.3±0.1kg.m−2) were separated into two groups of either a low or high abdominal to lower-body fat mass ratio [L-A/LB (n =11) or H-A/LB (n =10), respectively]. Lipoxmax and maximum lipid oxidation rate (MLOR) were determined during a submaximum incremental exercise test. Abdominal and lower-body fat mass were determined from DXA scans. Results The two groups did not differ in aerobic fitness, total fat mass, or total and localized fat-free mass. Lipoxmax and MLOR were significantly lower in H-A/LB vs L-A/LB women (43±3% VO2max vs 54±4% VO2max, and 4.8±0.6mgmin−1 kg FFM−1 vs 8.4±0.9mgmin−1 kg FFM−1, respectively; P <0.001). Total and abdominal fat mass measurements were negatively associated with Lipoxmax (r =–0.57 and r =–0.64, respectively; P <0.01) and MLOR [r =–0.63 (P <0.01) and r =–0.76 (P <0.001), respectively]. Conclusion These findings indicate that, in normal-weight women, a predominantly abdominal fat mass distribution compared with a predominantly peripheral fat mass distribution is associated with a lower capacity to maximize lipid oxidation during exercise, as evidenced by their lower Lipoxmax and MLOR.


      PubDate: 2014-04-05T01:42:05Z
       
  • Post-breakfast closed-loop glucose control is improved when accompanied
           with carbohydrate-matching bolus compared to weight-dependent bolus
    • Abstract: Publication date: Available online 19 March 2014
      Source:Diabetes & Metabolism
      Author(s): A. Haidar , D. Farid , A. St-Yves , V. Messier , V. Chen , D. Xing , A.-S. Brazeau , C. Duval , B. Boulet , L. Legault , R. Rabasa-Lhoret
      Aim We compared post-breakfast closed-loop glucose control either matched with a carbohydrate-matching bolus or a weight-dependent bolus. Methods Twelve adults with type 1 diabetes consumed a 75g CHO breakfast on two occasions. In random order, the breakfast was accompanied by a full carbohydrate-matching insulin bolus (8.30U [7.50U–11.50U]) or a partial weight-dependent insulin bolus (0.047U/kg; 3.45U [2.95U–3.75U]). Postprandial glucose was regulated by sensor-responsive insulin and glucagon delivery. Results Glucose control after the weight-dependent bolus was safe and feasible (glucose values returned to pre-prandial levels after 5h). However, 5-hr incremental area under the curve and percentage of time above 10mmol/L were lower after the full bolus compared to the partial bolus (IAUC, 2.1 [0.8–4.2]mmol/L/hr vs 8.3 [6.5–11.4] mmol/L/hr; time in hyperglycaemia, 24% [6%–29%] vs 50% [25%–63%]; P <0.001). Conclusions Post-breakfast closed-loop glucose control without carbohydrate counting, but based on weight-dependent bolus is feasible but a carbohydrate-matching bolus provides better glucose control. Clinical trial registry NCT01519102


      PubDate: 2014-03-21T07:16:38Z
       
  • Novel T-cell inhibiting peptides delay the onset of Type 1 diabetes in
           non-obese diabetic mice
    • Abstract: Publication date: Available online 11 March 2014
      Source:Diabetes & Metabolism
      Author(s): M.S. Wong , A. Tso , M. Ali , W.J. Hawthorne , N. Manolios
      The aim of this study was to investigate the effectiveness of immunomodulatory peptides in preventing the spontaneous onset of Type 1 diabetes in NOD mice. Two such peptides, CP and C1, were injected intraperitoneally in NOD mice three times a week starting at two different time points, nine weeks and 11weeks of age, and blood sugar levels monitored for the development of diabetes. CP was shown to be effective in delaying the onset of diabetes compared to control (P =0.006). The timing of peptide administration was crucial since delay in treatment did not prevent the onset of diabetes (nine weeks versus 11weeks of age). C1 was effective in delaying the onset of Type 1 diabetes with borderline significance when given at week 11 (P =0.05). These findings confirm the efficacy of these peptides in the prevention and possible treatment for Type 1 diabetes and thereby create new opportunities for genetic manipulation.


      PubDate: 2014-03-16T07:31:33Z
       
 
 
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