Diabetes & Metabolism (DIABETES METAB)

Publications in this journal

• Article: Skin autofluorescence is associated with past glycaemic control and complications in type 1 diabetes mellitus.

  M Genevieve, A Vivot, C Gonzalez, C Raffaitin, P Barberger-Gateau, H Gin, V Rigalleau
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  ABSTRACT: As skin autofluorescence (AF) can assess subcutaneous accumulation of fluorescent advanced glycation end-products (AGEs), this study aimed to investigate whether it was linked to glycaemic control and complications in patients with type 1 diabetes mellitus (T1DM). Using the AGE Reader™, AF was measured in T1DM patients referred to Haut-Levêque Hospital (Bordeaux, France); data on their HbA1c levels measured every 6months as far back as the last 5years were also collected. The association of AF with the patients' past glucose control, based on their latest HbA1c values, and the means of the last five and 10 HbA1c values, and with diabetic complications was also examined by linear regression analysis. The sample included 300 patients: 58% were male; the mean age was 49 (SD 17) years and the mean diabetes duration was 21 (SD 13) years. The median skin AF measurement was 2.0 [25th-75th percentiles: 1.7-2.4] arbitrary units (AU), and this was associated with age (β=0.15 per 10years, P<0.001) and diabetes duration (β=0.17 per 10years, P<0.001). After adjusting for age and estimated glomerular filtration rate (eGFR), the skin AF measurement was also related to the means of the last five and 10 HbA1c values (β=0.10 per 1% of HbA1c, P=0.005, and β=0.13 per 1% of HbA1c, P=0.001, respectively). In addition, the skin AF was associated with retinopathy (P<0.001), albuminuria (P<0.001) and decreased eGFR (P<0.001). In conclusion, the skin AF is related to the long-term glucose control and diabetic complications.
  Diabetes & Metabolism 05/2013;
• Article: Relationship between blood pressure, cognitive function and education level in elderly patients with diabetes: A preliminary study.

  J Talfournier, J Bitu, C Paquet, C Gobron, P J Guillausseau, J Hugon, J Dumurgier
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  ABSTRACT: AIMS: This study aimed to assess the relationship between blood pressure and cognitive function in elderly patients with diabetes mellitus (DM). METHODS: A total of 32 patients with DM aged≥65 years (seven women and 25 men; mean±SD age: 74.3±6.4 years) were included in this cross-sectional study. Relationships between blood pressure and neuropsychological tests were determined using Spearman's rank correlations (ρ) and multivariable linear regression models. RESULTS: Lower diastolic blood pressure was associated with lower scores on the Frontal Assessment Battery (ρ=0.32, P=0.02), longer times to complete the Trail Making Test Part B (ρ=0.51, P=0.003), lower scores for the Finger Tapping Test (ρ=0.36, P=0.046) and less verbal fluency (ρ=0.36, P=0.047). In multivariable models, these relationships were attenuated after adjusting for levels of education. CONCLUSION: There was an association between lower diastolic blood pressure and poorer executive function in this cohort of elderly DM patients. These results underline the importance of systematic cognitive evaluation in elderly patients with DM, and suggest that a too-low diastolic blood pressure may have deleterious effects on mental function. Larger studies in the future are required to confirm these preliminary results.
  Diabetes & Metabolism 05/2013;
• Article: Incretin dysfunction in type 2 diabetes: Clinical impact and future perspectives.

  B Ahrén
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  ABSTRACT: The incretin effect refers to the augmentation of insulin secretion after oral administration of glucose compared with intravenous glucose administration at matched glucose levels. The incretin effect is largely due to the release and action on beta-cells of the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). This system has in recent years had considerable interest due to the success of incretin therapy as a glucose-lowering strategy in type 2 diabetes. In non-diabetic subjects, the incretin effect is responsible for 50-70% of insulin release during oral glucose administration. In type 2 diabetes patients, the incretin effect is impaired and contributes to only 20-35% of the insulin response to oral glucose. The reason for the defective incretin effect in type 2 diabetes has been the subject of many studies. Although the reports in the literature are mixed, most studies of GIP and GLP-1 secretory responses to oral glucose or a mixed meal have shown fairly normal results in type 2 diabetes. In contrast, the insulinotropic effects of both GIP and GLP-1 are impaired in type 2 diabetes with greater suppression of insulin secretion augmentation with GIP than with GLP-1. The suggested causes of these defects are a defective beta-cell receptor expression or post-receptor defects secondary to the diabetes milieu, defective beta-cell function in general resulting in defective incretin effect and genetic factors initiating incretin hormone resistance. Identifying the mechanisms in greater detail would be important for understanding the strengths, weaknesses and efficacy of incretin therapy in individual patients to more specifically target this glucose-lowering therapy.
  Diabetes & Metabolism 05/2013;
• Article: Glycogen storage disease type 1 and diabetes: Learning by comparing and contrasting the two disorders.

  F Rajas, P Labrune, G Mithieux
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  ABSTRACT: Glycogen storage disease type 1 (GSD1) and diabetes may look at first like totally opposite disorders, as diabetes is characterized by uncontrolled hyperglycaemia, whereas GSD1 is characterized by severe fasting hypoglycaemia. Diabetes is due to a failure to suppress endogenous glucose production (EGP) in the postprandial state because of either a lack of insulin or insulin resistance. In contrast, GSD1 is characterized by a lack of EGP. However, both diseases share remarkably similar patterns in terms of pathophysiology such as the long-term progression of renal dysfunction and hepatic steatosis leading to renal failure and the development of hepatic tumours, respectively. Thus, much may be learned from considering the similarities between GSD1 and diabetes, especially in the metabolic pathways underlying nephropathy and fatty liver, and perhaps even more from their differences. In this review, the differences between diabetes and GSD1 are first highlighted, as both are characterized by alterations in EGP. The molecular pathways involved in liver pathologies, including steatosis, hepatomegaly (glycogenic hepatopathy) and the development of liver tumours are also compared. These pathologies are mainly due to the accumulation of lipids and/or glycogen in hepatocytes. Finally, the similar pathways leading to nephropathy in both diabetic and GSD1 patients are described. In conclusion, comparisons of these pathologies should lead to a better understanding of the crucial role of EGP in the control of glucose and energy homoeostasis. Moreover, it may highlight similar therapeutic targets for the two disorders. Thus, this review suggests that the treatment of adult patients with either GSD1 or diabetes could be carried out by the same specialists-diabetologists.
  Diabetes & Metabolism 05/2013;
• Article: Impaired endothelial function is not associated with arterial stiffness in adults with type 1 diabetes.

  G Llauradó, V Ceperuelo-Mallafré, C Vilardell, R Simó, L Albert, E Berlanga, J Vendrell, J M González-Clemente
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  ABSTRACT: AIM: This study investigated the relationship between endothelial dysfunction (ED) and arterial stiffness (AS) in adults with type 1 diabetes and no clinical cardiovascular (CV) disease. METHODS: A total of 68 patients with type 1 diabetes and 68 age- and gender-matched healthy (non-diabetic) subjects were evaluated. ED was assessed by reactive hyperaemia peripheral arterial tonometry (RH-PAT) and by serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin. AS was assessed by aortic pulse wave velocity (aPWV). All statistical analyses were stratified by gender. RESULTS: Adults with type 1 diabetes had RH-PAT index scores similar to those of their matching controls [men: 1.55 (1.38-1.98)% versus 1.61 (1.40-2.17)%, P=0.556; women: 2.07 (1.55-2.31)% versus 2.08 (1.79-2.49)%; P=0.215]. However, after adjusting for potential confounders, type 1 diabetes emerged as the main determinant of the RH-PAT index in women. Also, differences between genders in both the controls and type 1 diabetes patients disappeared. Men with diabetes had higher serum concentrations of E-selectin, and women had higher serum concentrations of sICAM-1, sVCAM-1 and E-selectin than their respective controls. However, after adjusting for potential confounders, only the differences in sICAM-1 (women) and E-selectin (both genders) remained significant. No association was found between aPWV and the RH-PAT index and ED markers after adjusting for CV risk factors. CONCLUSION: ED was increased in adults with type 1 diabetes compared with age-matched non-diabetic subjects. Also, gender differences in ED were lost in type 1 diabetes. However, ED was not associated with AS after adjusting for potential confounders. These findings suggest that ED occurs earlier than AS in type 1 diabetes.
  Diabetes & Metabolism 05/2013;
• Article: Prediction of macrosomia by serial sonographic measurements of fetal soft-tissues and the liver in women with pregestational diabetes.

  C Garabedian, A Vambergue, J Salleron, P Deruelle
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  ABSTRACT: OBJECTIVES: This study aimed to determine whether antenatal ultrasound measurements of fetal soft-tissues and liver can predict macrosomia in women with pregestational diabetes. METHODS: Fetal biometry, soft-tissue thickness (anterior abdominal wall [STAW], thigh [STT], upper arm [STA], scapular [STS]) and liver size were measured sonographically at 23, 28, 31 and 34 weeks of gestation. Large for gestational age (LGA) was defined as a birth weight greater than 90th percentile for gestational age on standard curves adjusted for maternal height and weight, parity and fetal gender. The area (±standard error) under receiver operating characteristic (AUROC) curves were also calculated. RESULTS: A total of 29 pregnant women with pregestational diabetes were included, and a total of 663 measurements taken. Fifteen neonates were LGA. There was no significant difference in fetal soft-tissue thickness at 23, 28 and 31 weeks between the LGA and non-LGA neonates. In contrast, at 34 weeks, fetal soft-tissues were significantly thicker in LGA neonates (P<0.05), but with no difference in liver surface area between the two groups. The specificity and sensitivity of 34-week ultrasonography to detect macrosomia was 78.6% and 66.7%, respectively, for abdominal circumference (AC), 71.4% and 93.3% for STT, 85.7% and 80.0% for STA, and 71.4% and 86.7% for STAW. No parameter was more powerful than the others. The best AUROC curves were found for AC (0.807), STT (0.821), STA (0.855) and STAW (0.821). CONCLUSION: Third-trimester sonographic measurements of fetal soft-tissue may help to detect macrosomia in pregnancies complicated by pregestational diabetes.
  Diabetes & Metabolism 05/2013;
• Article: Prevalence of treatment for diabetes during 1997-2007, and trends in cardiovascular risk factors between 2001 and 2007 according to diabetic treatment, in the IPC (Investigations Préventives et Cliniques; Preventive and Clinical Investigations) cohort.

  F Thomas, E Eschwege, K Bean, B Pannier, N Danchin
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  ABSTRACT: AIM: This study aimed to evaluate changes in the prevalence of glucose-lowering agents in a large, unselected general French population from 1997 to 2007, with specific focus on changes in other cardiovascular risk factors in relation to diabetic status during 2001-2002 and 2006-2007. METHODS: The prevalence of treated diabetes was assessed in a large population who had a health check-up at the "Investigations Préventives et Cliniques" Center between 1997-2007. Baseline characteristics and risk profiles of individuals with and without treatment for diabetes were assessed and compared with data for 2001-2002 and 2006-2007. RESULTS: From 1997 to 2007, the prevalence of treatment for diabetes increased from 0.75% to 1.73% in men and from 0.7% to 2.28% in women. In 2006-2007 compared with 2001-2002, the odds ratios for receiving glucose-lowering agents, adjusted for age, body mass index (BMI) and educational level, were 1.54 (95% CI: 1.28-1.86) in men and 1.59 (95% CI: 1.26-2.03) in women. In those treated for diabetes compared with untreated subjects, greater decreases in blood pressure, cholesterol and glycaemia were found, stress and depression scores improved, and a greater increase in BMI was found. Smoking decreased in both treated and untreated individuals. Physical activity decreased in treated individuals, but remained unchanged in the general population. CONCLUSION: The prevalence of people treated with diabetes increased in the Paris area. Although most concomitant risk factors decreased more in treated individuals than in the general population, physical activity and BMI worsened, thus, emphasizing the need for improving patient education.
  Diabetes & Metabolism 04/2013;
• Article: Effects of tactile massage on metabolic biomarkers in patients with type 2 diabetes.

  P E Wändell, J Arnlöv, A Nixon Andreasson, K Andersson, L Törnkvist, A C Carlsson
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  ABSTRACT: AIM: Tactile massage (TM) is a gentle and superficial form of massage. A pilot study of patients with type 2 diabetes in primary care reported a reduction of 0.8% in glycosylated haemoglobin (HbA1c), whereas a randomized study comparing the effects of 10weeks of TM once per week with relaxation exercises performed once per week as per instructions on a CD found no effects of TM on HbA1c in an intention-to-treat analysis. However, a significant reduction in waist circumference (WC) was found between the groups. METHODS: This was a secondary per-protocol analysis of the effect of TM (n=21) compared with relaxation (n=25) on other metabolic biomarkers. Anthropometrics (BMI and WC) and metabolic factors (B HbA1c, S IGF, fS insulin, S adiponectin, S leptin and fP ghrelin) were assessed, insulin resistance (IR) was determined by modified homoeostasis model assessment (HOMA2-IR) using fP glucose and fS insulin, and ratios of adiponectin-to-leptin, adiponectin-to-HOMA-IR, adiponectin-to-WC and adiponectin-to-HbA1c were calculated at baseline, and at 10weeks and 6months after the intervention. RESULTS: Significant results adjusted for age, gender and changes in lifestyle and medical factors were shown for WC in women (-6.2cm [95% CI: -10.4, -1.9]), but not in men. In addition, improvements in the TM group were found for adiponectin and ratios of adiponectin-to-leptin and adiponectin-to-HbA1c levels. CONCLUSION: Our data indicate that TM therapy may affect metabolic markers in type 2 diabetes despite the lack of significant effects on HbA1c. The clinical implications of our findings need to be evaluated in further studies.
  Diabetes & Metabolism 04/2013;
• Article: Treatment of diabetic ketoacidosis with subcutaneous insulin lispro: A review of the current evidence from clinical studies.

  M Vincent, E Nobécourt
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  ABSTRACT: AIM: Low-dose intravenous infusions of regular insulin, usually initiated in the emergency department and continued in the intensive care unit (ICU), are the standard care for patients with diabetic ketoacidosis (DKA) to ensure rapid resolution of hyperglycaemia and ketoacidosis. Several studies have evaluated whether subcutaneous injections of the rapid-acting analogue insulin lispro may be an alternative to intravenous insulin infusion for avoiding ICU admissions of uncomplicated DKA cases. METHODS: This review summarizes the current clinical evidence for the effectiveness and safety of subcutaneous insulin lispro injections in non-severe DKA patients. Relevant studies were identified by a systematic literature search through the PubMed database. RESULTS: To date, four small randomized studies (156 patients overall; three studies in adults and one in paediatric patients with diabetes) have directly compared subcutaneous insulin lispro injections every 1-2h vs continuous intravenous infusions of regular insulin. Patients with severe complications were excluded. In all studies, the mean time to resolution of DKA was similar in both treatment groups [range (three studies): lispro 10-14.8h; regular insulin 11-13.2h]. The mean time to resolution of hyperglycaemia, total insulin doses required, number of hospitalization days and number of hypoglycaemic episodes were similar in both treatment groups; no severe complications or DKA recurrences were reported, and one study showed a 39% cost reduction for the insulin lispro group. CONCLUSION: In patients with mild-to-moderate DKA, subcutaneous injections of insulin lispro every 1-2h offer a feasible alternative to continuous intravenous infusions of regular insulin, and should now be evaluated in larger, more appropriately powered studies.
  Diabetes & Metabolism 04/2013;
• Article: The association of type 2 diabetes and insulin resistance/secretion with persistent organic pollutants in two First Nations communities in northern Ontario.

  S Pal, J M Blais, M A Robidoux, F Haman, E Krümmel, T A Seabert, P Imbeault
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  ABSTRACT: AIMS: Recent evidence suggests an association between persistent organic pollutants (POPs) and type 2 diabetes. In two First Nations communities where wild food is consumed by a large portion of the population, we compared pollutants in plasma between diabetic and non-diabetic individuals, and investigated the strength of association between pollutants and insulin resistance/secretion in non-diabetic individuals. METHODS: The study population consisted of 72 participants. Oral Glucose Tolerance Tests were used to assess diabetes status. Plasma was used to determine POP concentrations and mercury concentrations were determined from hair samples. RESULTS: Age-adjusted plasma concentrations of some pollutants were significantly higher in diabetic than in non-diabetic individuals. When taking into account age, adiposity levels, and smoking status, POP levels were not associated with insulin resistance nor with insulin secretion in non-diabetic individuals. CONCLUSIONS: These findings confirm that POP concentrations in plasma may be higher in diabetic than in non-diabetic individuals. No association was however seen between POP concentrations and markers of insulin resistance/secretion in non-diabetic individuals.
  Diabetes & Metabolism 04/2013;
• Article: Interference of the most frequent haemoglobin variants on quantification of HbA1c: Comparison between the LC-MS (IFCC reference method) and three routinely used methods.

  S Jaisson, N Leroy, C Desroches, M Tonye-Libyh, E Guillard, P Gillery
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  ABSTRACT: AIM: Assaying HbA1c in patients with haemoglobin variants has long been a technical challenge, despite methodological advances that have progressively limited the problem. The purpose of this study was to evaluate the impact of the most frequent haemoglobin variants on three routine separation methods compared with the IFCC reference method. PATIENTS: Blood samples from heterozygous patients (AS, AC, AD, AE) were analyzed using the IFCC reference method (LC-MS), and the results compared with those obtained by capillary electrophoresis (CAPILLARYS 2 Flex Piercing, Sebia) and two HPLC methods using cation-exchange (Variant II, Bio-Rad) and affinity chromatography (Ultra(2), Primus). RESULTS: HbA1c values obtained by the IFCC reference method were comparable to those obtained by the three tested methods whatever the haemoglobin variant. Mean relative biases did not exceed the threshold of 7% (above which differences are generally considered clinically significant), although some individual values were above this limit with Variant II in samples with HbS and for all three methods in samples with HbE. CONCLUSION: This comparative study of the LC-MS reference method and three field methods has demonstrated that these assays are not clinically influenced by the presence of the most common haemoglobin variants. The present results also confirm that the interpretation of HbA1c values in patients with Hb variants remains complex and depends on the assays used and should, in some cases, take into account parameters other than analytical ones (such as differences in glycation rates and half-lives of haemoglobin variants).
  Diabetes & Metabolism 04/2013;
• Article: A novel GATA6 mutation leading to congenital heart defects and permanent neonatal diabetes: A case report.

  G Catli, A Abaci, S E Flanagan, E De Franco, S Ellard, A Hattersley, H Guleryuz, E Bober
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  ABSTRACT: Permanent neonatal diabetes mellitus is a rare condition mostly due to heterozygous mutations in the KCNJ11, ABCC8 and INS genes. Neonatal diabetes due to pancreatic agenesis is extremely rare. Mutations in PDX1, PTF1A, HNF1B, EIF2AK3, RFX6 and GATA6 genes have been shown to result in pancreatic agenesis or hypoplasia. This report describes a 40-day-old male infant diagnosed with permanent neonatal diabetes associated with atrial septal defect, pulmonary stenosis, patent ductus arteriosus and a novel de novo heterozygous missense mutation (p.N466S) in the GATA6 gene with no evidence of exocrine pancreas insufficiency. In addition to permanent neonatal diabetes, the patient had transient idiopathic neonatal cholestasis and hypoglycaemic episodes unrelated to insulin treatment, features that are rarely described in children with permanent neonatal diabetes.
  Diabetes & Metabolism 04/2013;
• Article: High prevalence of undiagnosed diabetes and high risk for diabetes using HbA1c criteria in middle-aged patients undergoing cataract surgery.

  S Feldman-Billard, N Sedira, P-Y Boelle, F Poisson, E Héron
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  ABSTRACT: AIM: This study assessed the prevalence of undiagnosed diabetes and a high risk for diabetes using glycated haemoglobin (HbA1c) values in middle-aged patients undergoing cataract surgery. METHODS: The study comprised 137 consecutive patients, aged 40 to 65 years, with no known diabetes undergoing cataract surgery at a French national eye centre. Fasting glucose, obesity parameters, and vascular and ocular cataract risk factors were recorded. HbA1c was measured on the day of cataract surgery. Prevalence of undiagnosed diabetes (HbA1c≥6.5%) and a high risk of diabetes (≥6.0% but<6.5%) in the study population was compared with recently published estimates from general French, Dutch and US populations. RESULTS: In the study population, undiagnosed diabetes was found in 12 patients (9%; 95% CI: 4-14%) and a high risk for diabetes in 47 (34%; 95% CI: 26-42%). These prevalences were four to 11 times higher than the corresponding population-based estimates, whereas obesity parameters recorded in the general populations and in our study population were similar according to HbA1c subcategories. Of the 125 patients with HbA1c less than 6.5%, values were higher in patients without ocular cataract risk factors (n=73; 58%) than in those with cataract risk factors (n=52; 42%) at 5.92±0.30% and 5.57±0.29%, respectively (P<0.001), thereby suggesting a significant role for blood glucose levels in cataractogenesis. CONCLUSION: Middle-aged patients undergoing cataract surgery showed a high prevalence of diabetes and a high risk for diabetes not recognized before surgery, suggesting that this patient population should be targeted for diabetes screening and prevention.
  Diabetes & Metabolism 04/2013;
• Article: SLC29A3 mutation in a patient with syndromic diabetes with features of pigmented hypertrichotic dermatosis with insulin-dependent diabetes, H syndrome and Faisalabad histiocytosis.

  J de Jesus, Z Imane, V Senée, S Romero, P-J Guillausseau, A Balafrej, C Julier
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  ABSTRACT: AIMS: Atypical forms of diabetes may be caused by monogenic mutations in key genes controlling beta-cell development, survival and function. This report describes an insulin-dependent diabetes patient with a syndromic presentation in whom a homozygous SLC29A3 mutation was identified. METHODS: SLC29A3 was selected as the candidate gene based on the patient's clinical manifestations, and all exons and flanking regions in the patient's genomic DNA were sequenced. RESULTS: A homozygous splice mutation (c.300+1G>C) resulting in a frameshift and truncated protein (p.N101LfsX34) was identified. The patient had insulin-dependent diabetes, congenital deafness, short stature, hyperpigmented patches on the skin, dysmorphic features, cardiomegaly, arthrogryposis, hepatosplenomegaly, anaemia with erythroblastopenia, and an inflammatory syndrome with fever and arthritis; she also presented with a fibrotic mediastinal mass. These clinical features overlapped with pigmented hypertrichosis with insulin-dependent diabetes (PHID), H syndrome, Faisalabad histiocytosis and sinus histiocytosis with massive lymphadenopathy (SHML), all of which are also caused by SLC29A3 mutations. CONCLUSION: This is the most severe case reported of SLC29A3 mutations with cumulative features of all these syndromes. This extreme severity coincides with the most N-terminal location of the truncation mutation, thereby affecting all alternative transcripts of the gene. This case report extends the clinical variability of homozygous SLC29A3 mutations that result in a spectrum of multisystemic manifestations.
  Diabetes & Metabolism 04/2013;
• Article: Transcription factor gene MNX1 is a novel cause of permanent neonatal diabetes in a consanguineous family.

  A Bonnefond, E Vaillant, J Philippe, B Skrobek, S Lobbens, L Yengo, M Huyvaert, H Cavé, K Busiah, R Scharfmann, M Polak, M Abdul-Rasoul, P Froguel, M Vaxillaire
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  ABSTRACT: AIM: Permanent neonatal diabetes mellitus (PNDM) is a rare monogenic form of non-autoimmune diabetes. Genetic defects have been identified in∼60% of cases, with mutations in ABCC8, KCNJ11 and INS being the most frequent causes of PNDM. Recognition of genetic subtypes strongly impacts on both patients' care and family counseling. This study aimed to identify the genetic aetiology of PNDM in a diabetic girl born of consanguineous parents. METHODS: DNA samples from both the proband and her non-diabetic parents were analyzed for homozygosity mapping, using Illumina Infinium 660K SNP microarrays, focusing on the runs of homozygosity (ROHs) detected only in the patient. Standard Sanger sequencing of candidate genes (MNX1 and GATA6) present in the ROHs was subsequently performed, as well as expression analyses on human embryonic and adult pancreatic islet samples. RESULTS: A putative causal homozygous mutation in the transcription factor gene MNX1 (c.816C>A/p.Phe272Leu) was identified in the PNDM patient, who was clinically diagnosed as a typical case of PNDM with no developmental pancreatic defects or other clinical features. The probable deleterious mutation was located within the MNX1 homeodomain helix 2 that is highly conserved between species. In human embryonic pancreatic islet samples, it has been shown that MNX1 expression is significantly enriched in pancreatic epithelium compared with mesenchyme, suggesting a role for MNX1 in human pancreatic beta-cell development. CONCLUSION: This study found a new putative cause of PNDM in a consanguineous family. Replication in other cohorts would help to clarify the clinical spectrum of MNX1 mutations in PNDM patients.
  Diabetes & Metabolism 04/2013;
• Article: Impact of objectively measured sedentary behaviour on changes in insulin resistance and secretion over 3years in the RISC study: Interaction with weight gain.

  E Lahjibi, B Heude, J M Dekker, K Højlund, M Laville, J Nolan, J-M Oppert, B Balkau
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  ABSTRACT: AIMS: The importance of reducing sedentary time is increasingly being recognized in the prevention of diabetes and cardiovascular disease. Despite this, the prospective association between sedentary time and physical activity with insulin sensitivity and cardiometabolic risk factors has been little studied. METHODS: In an analysis of data from the European RISC study, sedentary time and time spent in activity of moderate or vigorous intensity were assessed by accelerometry at baseline in 313 men and 414 women, aged 30-60years, with insulin sensitivity as measured by euglycaemic-hyperinsulinaemic clamp. Three years later, cardiometabolic risk factors (anthropometry, glucose, insulin, lipids) were available for 549 participants. RESULTS: In cross-sectional analyses using baseline data, after adjusting for age, gender, recruitment centre and time spent in activity of moderate or vigorous intensity, significant unfavourable associations were observed between higher sedentary time with body weight, HDL cholesterol, triglycerides, clamp-measured insulin sensitivity and insulin secretion (all Ptrend<0.002). Sedentary time remained significantly associated with insulin secretion after adjusting for insulin sensitivity (Ptrend=0.02). In longitudinal analyses, higher baseline sedentary time was associated with 3-year increases in fasting glucose, fasting insulin and the HOMA insulin-resistance index score for the 50% of the study population who increased their BMI by at least 0.3kg/m(2) (all Ptrend<0.01); these relationships remained significant after adjusting for time spent in activity of moderate or vigorous intensity. The 3-year increase in insulin secretion was lower in those spending more time doing activity of moderate or vigorous intensity (Ptrend=0.03). CONCLUSION: These prospective data suggest that less sedentary behaviour may partly counteract some of the negative effects of increasing body weight on glucose-insulin homoeostasis.
  Diabetes & Metabolism 03/2013;
• Article: Metformin revisited: A critical review of the benefit-risk balance in at-risk patients with type 2 diabetes.

  A J Scheen, N Paquot
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  ABSTRACT: Metformin is unanimously considered a first-line glucose-lowering agent. Theoretically, however, it cannot be prescribed in a large proportion of patients with type 2 diabetes because of numerous contraindications that could lead to an increased risk of lactic acidosis. Various observational data from real-life have shown that many diabetic patients considered to be at risk still receive metformin and often without appropriate dose adjustment, yet apparently with no harm done and particularly no increased risk of lactic acidosis. More interestingly, recent data have suggested that type 2 diabetes patients considered at risk because of the presence of traditional contraindications may still derive benefit from metformin therapy with reductions in morbidity and mortality compared with other glucose-lowering agents, especially sulphonylureas. The present review analyzes the benefit-risk balance of metformin therapy in special populations, namely, patients with stable coronary artery disease, acute coronary syndrome or myocardial infarction, congestive heart failure, renal impairment or chronic kidney disease, hepatic dysfunction and chronic respiratory insufficiency, all conditions that could in theory increase the risk of lactic acidosis. Special attention is also paid to elderly patients with type 2 diabetes, a population that is growing rapidly, as older patients can accumulate several comorbidities classically considered contraindications to the use of metformin. A review of the recent scientific literature suggests that reassessment of the contraindications of metformin is now urgently needed to prevent physicians from prescribing the most popular glucose-lowering therapy in everyday clinical practice outside of the official recommendations.
  Diabetes & Metabolism 03/2013;
• Article: Difficulty adhering to antidiabetic treatment: Factors associated with persistence and compliance.

  L Guénette, J Moisan, M-C Breton, C Sirois, J-P Grégoire
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  ABSTRACT: AIMS: This study aimed to assess the 1-year treatment persistence and compliance of new oral antidiabetic drug (OAD) users with their treatment, and to identify the factors associated with both persistence and compliance. METHODS: This population-based cohort study of new OAD users aged 18 years or above used the Quebec health insurance board databases. Those having a prescription filled for antidiabetic treatment during the period leading up to the 1-year anniversary of their first claim were considered to be persistent with their antidiabetic treatment. Of these patients, individuals with a medication possession ratio (MPR) greater or equal to 80% for OAD or insulin were deemed compliant. Also identified were the characteristics associated with both outcomes, using a multivariate logistic regression model. RESULTS: Our cohort consisted of 151,173 individuals, 119,832 (79.3%) of whom were considered persistent. Of these, 93,418 (78.0%) were also deemed compliant. Persistence and compliance were associated with older ages, living in a rural region, low socioeconomic status, having the first OAD prescribed by a general practitioner and a history of using five different drugs or more. People were less likely to be persistent and compliant if their initial OAD was a secretagogue and if they had consulted a physician eight times or more during the year prior to starting treatment. CONCLUSION: One year after OAD treatment initiation, 21% had discontinued their treatment and 22% of those still being treated were non-compliant. These results could help to tailor interventions aimed at optimizing the use of OAD treatments.
  Diabetes & Metabolism 03/2013;
• Article: Incretins: What is known, new and controversial in 2013?

  R Burcelin, B Thorens
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  ABSTRACT: Glucagon-like peptide (GLP)-1 action involves both endocrine and neural pathways to control peripheral tissues. In diabetes the impairment of either pathway may define different subsets of patients: some may be better treated with GLP-1 receptor agonists that are more likely to directly stimulate beta-cells and extrapancreatic receptors, while others may benefit from dipeptidyl peptidase (DPP)-4 inhibitor treatments that are more likely to increase the neural gut-brain-pancreas axis. Elevated plasma concentrations of GLP-1 associated with agonist treatment or bariatric surgery also appear to exert neuroprotective effects, ameliorate postprandial and fasting lipids, improve heart physiology and protect against heart failure, thereby expanding the possible positioning of GLP-1-based therapies. However, the mechanisms behind GLP-1 secretion, the role played by proximal and distal intestinal GLP-1-producing cells as well as the molecular basis of GLP-1 resistance in diabetes are still to be ascertained. The pharmacological features distinguishing GLP-1 receptor agonists from DPP-4 inhibitors are discussed here to address their respective positions in type 2 diabetes.
  Diabetes & Metabolism 03/2013;
• Article: MRI measurement of liver fat content predicts the metabolic syndrome.

  P-H Ducluzeau, J Boursier, S Bertrais, S Dubois, A Gauthier, V Rohmer, F Gagnadoux, G Leftheriotis, P Cales, R Andriantsitohaina, V Roullier, C Aubé
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  ABSTRACT: BACKGROUND AND AIMS: The prevalence of non-alcoholic fatty liver disease among cardiometabolic patients is not completely known because liver biopsy cannot be routinely performed. However, as magnetic resonance imaging (MRI) allows accurate and safe measurement of the hepatic fat fraction (HFF), the aim of this study was to quantify liver fat content in a dysmetabolic adult population. METHODS: A total of 156 adults were included in this cross-sectional study. Liver and visceral fat were assessed by MRI in these subjects, who presented with zero to five metabolic components of the metabolic syndrome (MetS). Arterial stiffness was recorded by ultrasonography, and the maximum Youden index was used to set the optimal HFF cutoff value predictive of the presence of the MetS. RESULTS: Overall, 72% of participants displayed three or more MetS components. HFF ranged from 0.3% to 52% (mean 13.4%). Age- and gender-adjusted HFF was positively correlated with BMI (r=0.44), blood pressure (r=0.19), triglyceridaemia (r=0.22) and glycaemia (r=0.31). MRI-measured visceral adipose tissue did not influence the relationship of steatosis with glycaemia, HOMA-IR and carotid stiffness, but there was a dose-response relationship between the number of MetS components and mean HFF. The optimal HFF for predicting the MetS was found to be 5.2% according to the maximum Youden index point. CONCLUSION: This study highlighted the impact of liver steatosis on cardiometabolic abnormalities with an optimal cutoff value of 5.2% for defining increased metabolic risk.
  Diabetes & Metabolism 03/2013;