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Journal Cover Diabetes & Metabolism
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     ISSN (Print) 1262-3636
     Published by Elsevier Homepage  [2563 journals]   [SJR: 0.871]   [H-I: 56]
  • 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
       
  • Colorectal cancer, diabetes and survival: Epidemiological insights
    • Abstract: Publication date: April 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 2
      Author(s): M.M.J. Zanders , P.A.J. Vissers , H.R. Haak , L.V. van de Poll-Franse
      Colorectal cancer (CRC) patients with pre-existing diabetes have significantly lower rates of overall survival compared with patients without diabetes. Against this backdrop, the American Diabetes Association and American Cancer Society in 2010 reviewed the scientific literature concerning diabetes and cancer. One of the key issues identified for further investigation was the need for a better understanding of whether diabetes influences cancer prognosis above and beyond the prognosis conferred by each disease state independently. Whether the worsened survival of CRC patients with diabetes could be explained by less favourable patient-, tumour- and treatment-related characteristics has also been evaluated in numerous recent studies. However, as most studies did not account for all the various potential confounders, such as cancer stage, comorbidities and body mass index (BMI) in their analyses, the current evidence for the association between diabetes and survival in CRC patients remains inconclusive. Nevertheless, based on multiple examples in the literature, the present review demonstrates that diabetes affects the presentation of CRC as well as its treatment and outcome, which may then result in lower overall rates of survival in patients with, compared to those without, diabetes.


      PubDate: 2014-04-20T06:45:12Z
       
  • Treating diabetes with islet transplantation: Lessons from the past decade
           in Lille
    • Abstract: Publication date: April 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 2
      Author(s): M.-C. Vantyghem , F. Defrance , D. Quintin , C. Leroy , V. Raverdi , G. Prévost , R. Caiazzo , J. Kerr-Conte , F. Glowacki , M. Hazzan , C. Noel , F. Pattou
      Type 1 diabetes (T1D) is due to the loss of both beta-cell insulin secretion and glucose sensing, leading to glucose variability and a lack of predictability, a daily issue for patients. Guidelines for the treatment of T1D have become stricter as results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. In this regard, glucometers, ambulatory continuous glucose monitoring, and subcutaneous and intraperitoneal pumps have been major developments in the management of glucose imbalance. Besides this technological approach, islet transplantation (IT) has emerged as an acceptable safe procedure with results that continue to improve. Research in the last decade of the 20th century focused on the feasibility of islet isolation and transplantation and, since 2000, the success and reproducibility of the Edmonton protocol have been proven, and the mid-term (5-year) benefit–risk ratio evaluated. Currently, a 5-year 50% rate of insulin independence can be expected, with stabilization of microangiopathy and macroangiopathy, but the possible side-effects of immunosuppressants, limited availability of islets and still limited duration of insulin independence restrict the procedure to cases of brittle diabetes in patients who are not overweight or have no associated insulin resistance. However, various prognostic factors have been identified that may extend islet graft survival and reduce the number of islet injections required; these include graft quality, autoimmunity, immunosuppressant regimen and non-specific inflammatory reactions. Finally, alternative injection sites and unlimited sources of islets are likely to make IT a routine procedure in the future.


      PubDate: 2014-04-20T06:45:12Z
       
  • Gastrointestinal changes after bariatric surgery
    • Abstract: Publication date: April 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 2
      Author(s): I. Quercia , R. Dutia , D.P. Kotler , S. Belsley , B. Laferrère
      Severe obesity is a preeminent health care problem that impacts overall health and survival. The most effective treatment for severe obesity is bariatric surgery, an intervention that not only maintains long-term weight loss but also is associated with improvement or remission of several comorbidies including type 2 diabetes mellitus. Some weight loss surgeries modify the gastrointestinal anatomy and physiology, including the secretions and actions of gut peptides. This review describes how bariatric surgery alters the patterns of gastrointestinal motility, nutrient digestion and absorption, gut peptide release, bile acids and the gut microflora, and how these changes alter energy homeostasis and glucose metabolism.


      PubDate: 2014-04-20T06:45:12Z
       
  • Adiponectin: A multitasking player in the field of liver diseases
    • Abstract: Publication date: April 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 2
      Author(s): T.E. Silva , G. Colombo , L.L. Schiavon
      Adiponectin is the most abundant adipokine synthesized by adipose tissue and has been shown to be a key component in the relationship between adiposity, insulin resistance and inflammation. It circulates in plasma at physiological concentrations that represent 0.05% of all plasma proteins. Adiponectin has trimeric, hexameric and multimeric forms that bind to receptors AdipoR1, AdipoR2 and T-cadherin especially in liver, muscle and endothelial cells. Adiponectin is considered a potent modulator of lipid and glucose metabolism with antidiabetic, antiatherogenic and anti-inflammatory properties, and plays an important role in the pathogenesis of metabolic diseases. The hepatoprotective effects of adiponectin, especially in non-alcoholic fatty liver disease (NAFLD), have been widely investigated, and its antisteatotic, anti-inflammatory and antifibrogenic effects have already been described. Adiponectin levels are reduced in individuals with fatty liver disease independently of body mass index, insulin resistance and other adipokines, and are inversely related to the severity of steatosis and necroinflammation, suggesting an important role in the relationship between adipose tissue, the liver and insulin sensitivity. Adiponectin has also been found to be reduced in cases of hepatitis B and C infection, and in cholestatic and autoimmune diseases, but is increased in patients with cirrhosis of different aetiologies. In addition, an important role for the liver in the regulation of adiponectin secretion by adipocytes, mediated by bile acids, has recently been proposed. The present report describes the importance of adiponectin in hepatic diseases as well as some future perspectives of the role of adiponectin as a biomarker and therapeutic target in liver diseases.


      PubDate: 2014-04-20T06:45:12Z
       
  • Re: Factors predictive of macrosomia in pregnancies with a positive oral
           glucose challenge test: Importance of fasting plasma glucose
    • Abstract: Publication date: April 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 2
      Author(s): O. Sanu



      PubDate: 2014-04-20T06:45:12Z
       
  • 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
       
  • Factors associated with screening for glucose abnormalities after
           gestational diabetes mellitus: Baseline cohort of the interventional
           IMPACT study
    • Abstract: Publication date: April 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 2
      Author(s): H. Bihan , E. Cosson , C. Khiter , L. Vittaz , F. Faghfouri , D. Leboeuf , L. Carbillon , H. Dauphin , G. Reach , P. Valensi
      Introduction Although it is important to screen women who have had gestational diabetes mellitus (GDM) for abnormal post-partum glucose levels, such testing is rarely performed. The aim of this study was to use data from the first observational phase of the IMPACT study to determine rates of screening within 6 months of delivery in a multiethnic cohort, focusing in particular on the effects of social deprivation and the risk of future diabetes. Patients and methods To investigate the frequency of post-partum screening, charts were analyzed, and all women attending four centres located in a deprived area who had had GDM between January 2009 and December 2010 were contacted by phone. The Evaluation of Precarity and Inequalities in Health Examination Centres (EPICES) deprivation index and Finnish Diabetes Risk Score (FINDRISK) questionnaire were also evaluated. Results Data were evaluable for 589 of the 719 women contacted (mean age: 33.4±5.2years; mean body mass index: 27.6±5.4kg/m2), and 196 (33.3%) reported having been screened. On multivariate analysis, factors associated with a lack of screening were smoking [odds ratio (OR): 0.42 (0.20–0.90), P <0.05], low consumption of fruit and vegetables [OR: 0.58 (0.39–0.82), P <0.01] and heavier offspring birth weight (P <0.05), although there were no differences in FINDRISK and EPICES scores between screened and unscreened women. Conclusion One-third of women who had had GDM reported having been screened for dysglycaemia at 6 months post-partum. However, it is expected that the interventional phase of the IMPACT study will increase screening rates, especially in women with the risk factors associated with lower screening rates during this observational phase.


      PubDate: 2014-04-20T06:45:12Z
       
  • Acute caloric restriction improves glomerular filtration rate in patients
           with morbid obesity and type 2 diabetes
    • Abstract: Publication date: April 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 2
      Author(s): I. Giordani , I. Malandrucco , S. Donno , F. Picconi , P. Di Giacinto , A. Di Flaviani , L. Chioma , S. Frontoni
      Aim The role of caloric restriction in the improvement of renal function following bariatric surgery is still unclear; with some evidence showing that calorie restriction can reduce proteinuria. However, data on the impact of caloric restriction on renal function are still lacking. Methods Renal function, as measured by glomerular filtration rate (GFR), was evaluated in 14 patients with type 2 diabetes mellitus, morbid obesity and stage 2 chronic kidney disease before and after a 7-day very low-calory diet (VLCD). Results After the VLCD, both GFR and overall glucose disposal (M value) significantly increased from 72.6±3.8mL/min/1.73m−2 BSA to 86.9±6.1mL/min/1.73m−2 BSA (P =0.026) and from 979±107μmol/min1/m2 BSA to 1205±94μmol/min1/m2 BSA (P =0.008), respectively. A significant correlation was observed between the increase in GFR and the rise in M value (r =0.625, P =0.017). Conclusion Our observation of improved renal function following acute caloric restriction before weight loss became relevant suggesting that calory restriction per se is able to affect renal function.


      PubDate: 2014-04-20T06:45:12Z
       
  • Type 2 diabetes prevalence, health status and quality of care among the
           North African immigrant population living in France
    • Abstract: Publication date: April 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 2
      Author(s): S. Fosse-Edorh , A. Fagot-Campagna , B. Detournay , H. Bihan , A. Gautier , M. Dalichampt , C. Druet
      Aim This report is an overview of type 2 diabetes (DT2) in the North African immigrant population living in France. Methods Data were collected in two separate cross-sectional national surveys. DT2 prevalence was estimated using a population-based survey involving 13 959 people aged ≥ 45 years (EDS), while health status and quality of care were evaluated using a sample of 3894 DT2 patients (ENTRED). Results Prevalence of DT2 and obesity was 14.0% [CI 95%: 9.9; 18.0] and 20.5% [15.7; 25.3], respectively, in participants born in North Africa (BNA) and 7.5% [7.0; 8.0] and 15.8% [14.7; 16.8], respectively, in those born in France (BIF). DT2 was associated with region of birth in women after adjusting for age, body mass index and income or occupation, but not after adjusting for education level. In men, DT2 was not associated with region of birth. BNA and BIF patients with diabetes frequently benefited from free medical coverage (88% vs. 84%, respectively), although BNA diabetic patients visited a general practitioner less frequently than BIF (8.5 vs. 9.0 visits/year, respectively). The percentage of BNA vs. BIF diabetes patients tested three times a year for HbA1c was lower (39% vs. 44%), while HbA1c was higher in BNA vs. BIF diabetics (> 8%: 30% vs. 15%). Ophthalmological complications were also more frequent in BNA vs. BIF patients with diabetes (25% vs. 18%, respectively). Conclusion The greater prevalence of DT2 in BNA women and the poorer glycaemic control observed in the BNA population overall both probably contribute to disparity in diabetes mortality compared with BIF diabetics, a fact that has been observed in previous studies.


      PubDate: 2014-04-20T06:45:12Z
       
  • Ketoacidosis at diagnosis of type 1 diabetes in French children and
           adolescents
    • Abstract: Publication date: April 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 2
      Author(s): C. Choleau , J. Maitre , A. Filipovic Pierucci , C. Elie , P. Barat , A.-M. Bertrand , M. de Kerdanet , C. Letallec , C. Levy-Marchal , M. Nicolino , N. Tubiana-Rufi , M. Cahané , J.-J. Robert
      Objectives This study aimed to evaluate the frequency of diabetic ketoacidosis (DKA) and its associated factors at the diagnosis of type 1 diabetes (T1D) in French children and adolescents prior to launching a public-health campaign of information to prevent DKA. Patients and methods Over a 1-year period, 1299 youngsters (aged<15 years) were diagnosed with T1D at 146 paediatric centres in all regions of France. Age, gender, duration of symptoms, patient's pathway to diagnosis, clinical and biological signs, and family history of T1D were collected for each newly diagnosed patient. DKA was defined as pH<7.30 or bicarbonate<15mmol/L, and severe DKA as pH<7.10 or bicarbonate<5mmol/L. Results At the time of diagnosis, 26% of the children were aged 0–5 years, 34% were 5–10 years and 40% were 10–15 years. The overall prevalence of DKA was 43.9% (0–5 years: 54.2%; 5–10 years: 43.4%; and 10–15 years: 37.1%) and 14.8% for severe DKA (0–5 years: 16.6%; 5–10 years: 14.4%; and 10–15 years: 13.9%;<2 years: 25.3%). Severe DKA was more frequent when the child was hospitalized at the family's behest (26.6%) than when referred by a general practitioner (7.6%) or paediatrician (5.1%; 30.6%, 53.7% and 9.2%, respectively, by patients’ age group). The frequency of DKA decreased to 20.1% (severe DKA: 4.4%) in families with a history of T1D. Multivariate analysis showed that age, pathway to diagnosis, duration of polyuria/polydipsia (< 1 week) and family history of T1D were associated with the presence of DKA, while pathway to diagnosis and family history of T1D were associated with severe DKA. Conclusion DKA at the time of T1D diagnosis in children and adolescents is frequent and often severe. Patients’ age, pathway to hospitalization and family history of diabetes were the main factors associated with DKA. These data suggest that a public-health campaign to prevent DKA at diagnosis can help reduce the frequency of DKA and also provide baseline data for evaluating the efficacy of such a campaign.


      PubDate: 2014-04-20T06:45:12Z
       
  • Autonomic function is not associated with the incidence of type 2 diabetes
           in a high-risk population: The Hoorn study
    • Abstract: Publication date: April 2014
      Source:Diabetes & Metabolism, Volume 40, Issue 2
      Author(s): S. Hillebrand , R. de Mutsert , M. den Heijer , S. le Cessie , C.D.A. Stehouwer , G. Nijpels , J.M. Dekker
      Aim Impaired autonomic function is a complication of type 2 diabetes mellitus (DM2), but may also be involved in its development. For this reason, this study looked at the association of autonomic function with the incidence of DM2 in a homogeneous Caucasian population. Methods This Hoorn study was a prospective population-based study of individuals aged 50–75 years. For the 631 participants, the standard deviation of all normal-to-normal intervals (SDNN) and eight other parameters of autonomic function were calculated at baseline. Fasting and 2-h glucose were measured during follow-up by oral glucose tolerance test (OGTT). DM2 at baseline and follow-up was ascertained by questionnaire and OGTT. After excluding participants with DM2 at baseline, the association of parameters of autonomic function with incident diabetes was examined using logistic-regression analysis while adjusting for possible confounders. Results After excluding those with known (n =67) or newly diagnosed (n =126) DM2 at baseline and those missing follow-up data (n =140), 298 participants were eligible for the study (182 with normal glucose tolerance, 19 with impaired fasting glucose and 97 with impaired glucose tolerance). During a median follow-up of 9.2 (range 4.5–11.1) years, 94 incident cases of DM2 were observed. After adjusting for confounding variables, the DM2 odds ratio was 1.12 (95% CI: 0.77, 1.64) per SDNN increase. Results for other parameters of autonomic function were similar. Conclusion The present study found no evidence of an association between autonomic function and DM2 incidence in a population at high risk of diabetes. This implies that previously observed associations between autonomic function and glucose metabolism in cross-sectional settings may reflect reverse causation.


      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
       
  • Measurement of muscle insulin sensitivity in obese men
    • Abstract: Publication date: Available online 19 March 2014
      Source:Diabetes & Metabolism
      Author(s): M. Wilson , R. Ross
      Aims In 2007, a novel estimate of skeletal muscle insulin sensitivity was derived from the oral glucose tolerance test (OGTT). The aim of this investigation is to assess whether and to what extent the proposed index of skeletal muscle insulin sensitivity derived from the OGTT was associated with muscle insulin sensitivity measured using the hyperinsulinemic-euglycaemic clamp technique. Methods Forty-six middle-aged, abdominally obese men (age 44±8years, waist circumference 107.4±6.2) were studied. Each participant participated in a 2-hour, 75-g OGTT and a 3-hour hyperinsulinemic-euglycaemic clamp protocol. Results The OGTT-derived index of muscle insulin sensitivity correlated with muscle insulin sensitivity measured with the insulin clamp (r =0.55, P <0.01), however, the standard error of estimate (SEE) when predicting muscle insulin sensitivity by the OGTT-derived index was 5.3 (50%). Conclusion Our findings suggest that despite a statistically significant association between the two methods, the OGTT approach lacks precision and is not a useful method for estimating skeletal muscle insulin sensitivity in abdominally obese men.


      PubDate: 2014-03-21T07:16:38Z
       
  • 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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