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Aim: To evaluate the associations between metabolically healthy obesity (MHO) and different types of incident cardiovascular events in a contemporary population. Materials and Methods: All patients discharged from French hospitals in 2013 with at least 5 years of follow‐up and without a history of major adverse cardiovascular event (MACE; myocardial infarction, heart failure [HF], ischaemic stroke or cardiovascular death [MACE‐HF]) or underweight/malnutrition were identified. They were categorized by phenotypes defined by obesity and three metabolic abnormalities (diabetes, hypertension and hyperlipidaemia). Hazard ratios (HRs) for cardiovascular events during follow‐up were adjusted on age, sex and smoking status at baseline. Results: In total, 2 873 039 individuals were included in the analysis, among whom 272 838 (9.5%) had obesity. During a mean follow‐up of 4.9 years, when pooling men and women, individuals with MHO had a higher risk of MACE‐HF (multivariate‐adjusted HR 1.22, 95% confidence interval [CI]: 1.19‐1.24), new‐onset HF (HR 1.34, 95% CI 1.31‐1.37) and atrial fibrillation (AF; HR 1.33, 95% CI 1.30‐1.37) compared with individuals with no obesity and zero metabolic abnormalities. By contrast, risks were not higher for myocardial infarction (HR 0.92, 95% CI 0.87‐0.98), ischaemic stroke (HR 0.93, 95% CI 0.88‐0.98) and cardiovascular death (HR 0.99, 95% CI 0.93‐1.04). MHO in men was associated with a higher risk of clinical events compared with metabolically healthy men of normal weight (HR 1.12‐1.80), while women with MHO had a lower risk for most events than metabolically healthy women of normal weight (HR 0.49‐0.99). Conclusions: In a large and contemporary analysis of patients seen in French hospitals, individuals with MHO did not have a higher risk of myocardial infarction, ischaemic stroke or cardiovascular death than metabolically healthy individuals with no obesity. By contrast, they had a higher risk of new‐onset HF and new‐onset AF. However, notable differences were observed in men and women in the sex‐stratified analysis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether the association between obstructive sleep apnea severity and glucose control differs between patients with newly diagnosed and untreated type 2 diabetes, and patients with known and treated type 2 diabetes. This multicentre cross-sectional study included 762 patients investigated by sleep recording for suspected obstructive sleep apnea, 497 of whom were previously diagnosed and treated for type 2 diabetes (treated diabetic patients), while 265 had no medical history of diabetes but had fasting blood glucose ≥126 mg dL−1 and/or glycated haemoglobin (HbA1c) ≥6.5% consistent with newly diagnosed type 2 diabetes (untreated diabetic patients). Multivariate regression analyses were performed to evaluate the independent association between HbA1c and obstructive sleep apnea severity in treated and untreated patients with diabetes. In untreated diabetic patients, HbA1c was positively associated with apnea-hypopnea index ( P = 0.0007) and 3% oxygen desaturation index ( P = 0.0016) after adjustment for age, gender, body mass index, alcohol habits, metabolic dyslipidaemia, hypertension, statin use and study site. The adjusted mean value of HbA1c increased from 6.68% in the lowest quartile of the apnea-hypopnea index (<17) to 7.20% in the highest quartile of the apnea-hypopnea index (>61; P = 0.033 for linear trend). In treated patients with diabetes, HbA1c was associated with non-sleep variables, including age, metabolic dyslipidaemia and insulin use, but not with obstructive sleep apnea severity. Obstructive sleep apnea may adversely affect glucose control in patients with newly diagnosed and untreated type 2 diabetes, but may have a limited impact in patients with overt type 2 diabetes receiving anti-diabetic medications. [ABSTRACT FROM AUTHOR]

OBJECTIVE--The pathophysiological mechanisms to explain the association between risk of type 2 diabetes and elevated concentrations of γ/-glutamyltransferase (GGT) and alanineaminotransferase (ALT) remain poorly characterized. We explored the association of liver enzymes with peripheral and hepatic insulin resistance, insulin secretion, insulin clearance, and glucagon concentration. RESEARCH DESIGN AND METHODS--We studied 1,309 nondiabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study; all had a euglycemic-hyperinsulinemic clamp and an oral glucose tolerance test (OGTT) with assessment of insulin secretion and hepatic insulin extraction. The hepatic insulin resistance index was calculated in 393 individuals. RESULTS--In both men and women, plasma concentrations of GGT and ALT were inversely related with insulin sensitivity (M/I) (all P < 0.01). Likewise, the hepatic insulin resistance index was positively correlated with both GGT (r = 0.37, P < 0.0001, men; r = 0.36, P < 0.0001, women) and ALT (r = 0.25, P = 0.0005, men; r = 0.18, P = 0.01, women). These associations persisted in multivariable models. Increased GGT and ALT were significantly associated with higher insulin secretion rates and with both reduced endogenous clearance of insulin and hepatic insulin extraction during the OGTT (P = 0.0005 in men; P = 0.003 in women). Plasma fasting glucagon levels increased over ALT quartiles (men, quartile 4 vs. quartile 1 11.2 ± 5.1 vs. 9.3 ± 3.8 pmol/L, respectively, P = 0.0002; women, 9.0 ± 4.3 vs. 7.6 ± 3.1, P = 0.001). CONCLUSIONS--In healthy individuals, increased GGT and ALT were biomarkers of both systemic and hepatic insulin resistance with concomitant increased insulin secretion and decreased hepatic insulin clearance. The novel finding of a positive correlation between ALT and fasting glucagon level concentrations warrants confirmation in type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--The clinical expression of maturity-onset diabetes of the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-α (HNF1A) gene mutation. RESEARCH DESIGN AND METHODS--We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis of diabetes. RESULTS--Missense mutations prevailed in the dimerization and DNA-binding domains (74%), while truncating mutations were predominant in the transactivation domain (62%). The majority (83%) of the mutations were located in exons 1- 6, thus affecting the three HNF1A isoforms. Age at diagnosis of diabetes was lower in patients with truncating mutations than in those with missense mutations (18 vs. 22 years, P = 0.005). Missense mutations affecting the dimerization/DNA-binding domains were associated with a lower age at diagnosis than those affecting the transactivation domain (20 vs. 30 years, P = 10-4). Patients with missense mutations affecting the three isoforms were younger at diagnosis than those with missense mutations involving one or two isoforms (P = 0.03). CONCLUSIONS--These data show that part of the variability of the clinical expression in MODY3 patients may be explained by the type and the location of HNF1A mutations. These findings should be considered in studies for the search of additional modifier genetic factors. Diabetes 57:503-508, 2008 [ABSTRACT FROM AUTHOR]

Examines the clinical presentation of maternally inherited diabetes and deafness (MIDD) in France.

To investigate whether diabetes confers higher relative risks of cardiovascular events in women compared with men using contemporary data and also whether such gender-differences are dependent on age. All patients discharged from French hospitals in 2013 with at least 5 years of follow-up and no history of major adverse cardiovascular events including heart failure (MACE-HF; heart failure, myocardial infarction, ischaemic stroke, cardiovascular death) were identified and categorized by diabetes status. Overall and age-stratified incidence rates, hazard ratios (HRs) and women-to-men ratios (WMRs) for MACE-HF leading to hospitalization were also calculated. Adjustments were then made for age and baseline characteristics according to cardiovascular risk factors and non-cardiovascular comorbidities. The study included 2,953,816 subjects, among whom 349,928 (11.9%) had diabetes. Of those with diabetes, the absolute rate of MACE-HF was higher in men than in women (96 vs 66 per 1000 person-years); corresponding absolute rates in men and women without diabetes were 44 vs 27 per 1000 person-years. Comparing those with and without diabetes, women had a higher unadjusted HR of MACE-HF (2.45, 95% CI: 2.42–2.47) than men (2.15, 95% CI: 2.14–2.17), with an adjusted WMR of 1.13 (95% CI: 1.12–1.15). HRs of MACE-HF related to diabetes were highest in women aged around 45 years and in the youngest men and decreased with advancing age in both these groups. However, HRs were higher in women of all ages > 40 years. After adjustment, this effect was more apparent for myocardial infarction (adjusted WMR: 1.43, 95% CI: 1.38–1.48) than for either ischaemic stroke (adjusted WMR: 1.10, 95% CI: 1.07–1.14) or heart failure (adjusted WMR: 1.13, 95% CI: 1.11–1.14). Although men have higher absolute risks of cardiovascular complications, the relative risks of cardiovascular complications associated with diabetes are higher in women than in men. [ABSTRACT FROM AUTHOR]

Abstract: Low-dose aspirin is largely but non-homogeneously used in primary prevention of cardiovascular complication in type-2 diabetic patients. We hypothesised that low-dose aspirin could interfere with the cutaneous neurovascular responses in type-2 diabetic patients. Galvanic current-induced vasodilatation (CIV) is an original non-noxious integrative model of neurovascular interaction and is impaired under low-dose aspirin in healthy subjects. Twenty type-2 diabetic patients (ten not receiving aspirin: D-NA and ten regularly receiving ≤150 mg/day aspirin: D-A), and ten age-, BMI-, and gender-matched non-diabetic control volunteers (MC), underwent macro- and microvascular investigations, including: CIV, acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis, post-occlusive hyperemia (POH), neuropathy symptom (NSS) and disability (NDS) scores, and thermal and vibration sensory thresholds. Results are presented as median [25–75 centile] and microvascular results are expressed in multiple from baseline conductance (%Cb). CIV was 554 [349–769] %Cb in MC, 251 [190–355] %Cb in D-NA and 159 [136–202] %Cb in D-A (p <0.05). No differences were observed between the three groups except for CIV, which is impaired in diabetic patients and further impaired in those regularly receiving low-dose aspirin, while other macrovascular, microvascular and clinical-sensitivity investigations show no significant difference. Potential clinical markers for the impairment of the neurovascular interaction are still required in diabetes. Correlation of the CIV response with the risk of cutaneous complications in diabetic patients remains to be tested. [Copyright &y& Elsevier]