We aimed to analyze the shape of the glucose, insulin, and C-peptide curves during a 3-h oral glucose tolerance test (OGTT). Another aim was defining an index of shape taking into account the whole OGTT pattern. Five-hundred ninety-two OGTT curves were analyzed, mainly from women with former gestational diabetes, with glycemic concentrations characterized by normal glucose tolerance ( n = 411), impaired glucose metabolism ( n = 134), and Type 2 diabetes ( n = 47). Glucose curves were classified according to their shape (monophasic, biphasic, triphasic, and 4/5-phases), and the metabolic condition of the subjects, divided according to the glucose shape stratification, was analyzed. Indices of shape based on the discrete second-order derivative of the curve patterns were also defined. We found that the majority of the glucose curves were monophasic ( n = 262). Complex shapes were less frequent but not rare ( n = 37 for the 4/5-phases shape, i.e., three peaks). There was a tendency toward the amelioration of the metabolic condition for increasing complexity of the shape, as indicated by lower glucose concentrations, improved insulin sensitivity and β-cell function. The shape index computed on C-peptide, WHOSHCP (WHole-Ogtt-SHape-index–C-peptide), showed a progressive increase [monophasic: 0.93 ± 0.04 (dimensionless); 4/5-phases: 1.35 ± 0.14], and it showed properties typical of β-cell function indices. We also found that the type of glucose shape is often associated to similar insulin and C-peptide shape. In conclusion, OGTT curves can be characterized by high variability, and complex OGTT shape is associated with better glucose tolerance. WHOSHCP (WHole-Ogtt-SHape-index) may be a powerful index of β-cell function much simpler than model-based indices.

OBJECTIVEThere is growing evidence that osteocalcin, an osteoblast-derived protein locally acting on bone formation, can increase insulin secretion as well as insulin sensitivity and thus prevent the development of obesity and diabetes in experimental animals. In humans, osteocalcin has been reported to be decreased in patients with type 2 diabetes. Because gestational diabetes mellitus (GDM) can serve as a model of pre–type 2 diabetes, the aim of this study was to investigate osteocalcin in GDM.RESEARCH DESIGN AND METHODSOsteocalcin measurement and an oral glucose tolerance test were performed in 78 pregnant women (26 women had GDM and 52 women had normal glucose tolerance [NGT] during pregnancy; women were matched for age and BMI) and in 34 women postpartum.RESULTSDuring pregnancy osteocalcin was significantly higher in the women with GDM than in the women with NGT (15.6 ± 6.4 vs. 12.6 ± 4.0 ng/ml; P < 0.015), whereas no difference was observed between the two groups at 12 weeks postpartum (36.2 ± 10.2 vs. 36.2 ± 13.0 ng/ml), when osteocalcin was found to be increased compared with the level in the pregnant state in all women (+145 ± 102% in GDM vs. +187 ± 119% in NGT; P < 0.0001). Moreover, osteocalcin showed a significant correlation with basal and total insulin secretion in the whole study group (R = 0.3, P < 0.01).CONCLUSIONSIn GDM osteocalcin was higher and thus less restrained than in women with NGT during pregnancy and furthermore correlated with insulin secretion parameters. Therefore, it could be hypothesized that osteocalcin can enhance insulin secretion in insulin-resistant states; alternatively an effect of hyperinsulinemia on osteocalcin secretion cannot be excluded.

CS appears to be a rare cause of morbid obesity. Normalization of slightly elevated thyrotropin after weight loss suggests that obesity causes TSH elevation rather than the reverse.

Increased myocardial lipid content (MYCL) recently has been linked to the development of cardiomyopathy in diabetes. In contrast to steatosis in skeletal muscle and liver, previous investigations could not confirm a link between MYCL and insulin resistance. Thus, we hypothesized that cardiac steatosis might develop against the background of the metabolic environment typical for prediabetes and early type 2 diabetes: combined hyperglycemia and hyperinsulinemia. Therefore, we aimed to prove the principle that acute hyperglycemia (during a 6-h clamp) affects MYCL and function (assessed by 1H magnetic resonance spectroscopy and imaging) in healthy subjects (female subjects: n = 8, male subjects: n = 10; aged 28 ± 5 years; BMI 22.4 ± 2.6 kg/m2). Combined hyperglycemia (202.0 ± 10.6 mg/dL) and hyperinsulinemia (110.6 ± 59.0 μU/mL) were, despite insulin-mediated suppression of free fatty acids, associated with a 34.4% increase in MYCL (baseline: 0.20 ± 0.17%, clamp: 0.26 ± 0.22% of water signal; P = 0.0009), which was positively correlated with the area under the curve of insulin (R = 0.59, P = 0.009) and C-peptide (R = 0.81, P < 0.0001) during the clamp. Furthermore, an increase in ejection fraction (P < 0.0001) and a decrease in end-systolic volume (P = 0.0002) were observed, which also were correlated with hyperinsulinemia. Based on our findings, we conclude that combined hyperglycemia and hyperinsulinemia induce short-term myocardial lipid accumulation and alterations in myocardial function in normal subjects, indicating that these alterations might be directly responsible for cardiac steatosis in metabolic diseases.

Aim of this study was analyzing the time trajectories of the metabolic parameters in European women with former gestational diabetes (fGDM), and determining predictors of type 2 diabetes onset. A group of seventy-six fGDM women were studied at the outpatient department of the University Clinic of Vienna. They were evaluated yearly with a 3 h-oral glucose tolerance test (OGTT) up to 7-years from delivery. At baseline, women also underwent an intravenous glucose tolerance test (IVGTT). Insulin sensitivity and beta-cell function were assessed by both OGTT and IVGTT. Women were divided into progressors (PROG) to diabetes (n = 19) and non-progressors (n = 57). Time trajectories of glycemia and other parameters were analyzed after synchronization to time of diabetes onset or last OGTT. Then, Cox proportional hazard regression analysis was performed to assess the predictive power of studied variables for diabetes onset. We found that, in PROG, time trajectories of glycemia were flat until diabetes onset, when they showed a marked increase (P<0.0001). Insulin sensitivity showed similar marked decrease (P<0.0001) at diabetes onset, together with a tendency to continuous slow decline in the previous years. At contrast, beta-cell function showed only continuous slow decline. Major predictors of diabetes onset were glycemic levels, BMI, insulin resistance, and condition of impaired glucose tolerance. In conclusion, in fGDM, marked deterioration of insulin sensitivity is associated with diabetes onset. Prevention strategies aimed at opposing to the insulin sensitivity derangement may be particularly beneficial.

Summary Background The obesity epidemic might affect patients with type 1 diabetes (T1DM), historically described as lean and insulin-sensitive subjects. Insulin resistance in T1DM might increase diabetic complications, especially cardiovascular disease. Therefore, the body mass index (BMI) in T1DM patients was analyzed in comparison to the general population. Furthermore, the impact of increased BMI on glycemic control and metabolic alterations was assessed. Methods Body mass index was compared overall and among four different age groups between adult T1DM ( n = 186), treated in the outpatient clinic between 2014 and 2016, and 15,771 individuals from the general population who took part at an Austrian health survey. Furthermore, parameters of glycemic control, lipid state, blood pressure and additional medication were compared between T1DM with a BMI under or above 27.5 kg/m 2 . Results Patients with T1DM had significantly higher BMI values than general population (25.9 ± 4.2 kg/m 2 vs. 25.3 ± 4.5 kg/m 2 ; p = 0.027), controlling for age group; however, prevalence of overweight (39.8% vs. 33.1%) and obesity (14% vs. 13.8%) was not significantly different. Within the 4 age groups only T1DM patients between 30 years and 49 years old had significantly higher BMI values compared to the general population (mean difference 1.9 kg/m 2 ; 95% confidence interval, CI: 0.96–2.83 kg/m 2 ). In T1DM, a BMI ≥27.5 kg/m 2 was associated with increased rates of hypertension, dyslipidemia, microalbuminuria, and increased insulin demand, whereas glycemic control was not affected. Conclusions In contrast to common descriptions T1DM patients have a higher BMI compared to the general population. Rates of overweight and obesity in T1DM equal those of the general population. Therefore, it is concluded that the obesity epidemic has reached T1DM patients and “double diabetes” might be an entity to consider.

Acromegaly represents a unique condition characterized by low myocardial and hepatic lipid content despite decreased insulin sensitivity, hyperinsulinemia, and hyperglycemia. Hence, ectopic lipid accumulation does not appear to contribute to cardiac morbidity, and increased lipid oxidation might counteract ectopic lipid accumulation in GH excess.

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