Reference ranges of HOMA-IR in normal-weight and obese young Caucasians.

AIMS: Insulin resistance (IR) may develop very early in life being associated with occurrence of cardiometabolic risk factors (CMRFs). Aim of the present study was to identify in young Caucasians normative values of IR as estimated by the homeostasis model assessment (HOMA-IR) and cutoffs diagnostic of CMRFs. METHODS: Anthropometrics and biochemical parameters were assessed in 2753 Caucasians (age 2-17.8 years; 1204 F). Reference ranges of HOMA-IR were defined for the whole population and for samples of normal-weight and overweight/obese individuals. The receiver operator characteristic analysis was used to find cutoffs of HOMA-IR accurately identifying individuals with any CMRF among total cholesterol and/or triglycerides higher than the 95th percentile and/or HDL cholesterol lower than the 5th for age and sex, impaired glucose tolerance, and alanine aminotransferase levels ≥40 U/l. RESULTS: Overweight/obese individuals had higher HOMA-IR levels compared with normal-weight peers (p < 0.0001) at any age. HOMA-IR index rose progressively with age, plateaued between age 13 and 15 years and started decreasing afterward. HOMA-IR peaked at age 13 years in girls and at 15 years in boys. The 75th percentile of HOMA-IR in the whole population (3.02; AUROC = 0.73, 95 % CI = 0.70-0.75), in normal-weight (1.68; AUROC = 0.76, 95 % CI = 0.74-0.79), and obese (3.42; AUROC = 0.71, 95 % CI = 0.69-0.72) individuals identified the cutoffs best classifying individuals with any CMRF. CONCLUSIONS: Percentiles of HOMA-IR varied significantly in young Caucasians depending on sex, age, and BMI category. The 75th percentile may represent an accurate cutoff point to suspect the occurrence of one or more CMRFs among high total cholesterol and triglycerides, low HDL cholesterol, and ALT ≥ 40 UI/l.

Insulin sensitivity from preschool to school age in patients with severe obesity.

BACKGROUND: Insulin sensitivity decreases at puberty transition, but little information has been provided on its earlier time-course. Aim of the present study was to describe the time-course of insulin sensitivity in severely obese children at the transition from preschool to school age. RESEARCH DESIGN AND METHODS: Retrospective study of a cohort of 47 severely obese [Body Mass Index (BMI) ≥99° percentile] preschoolers evaluated twice, once between 2 and 6 years of age, and once before age 8. Glucose tolerance, Whole Body Insulin Sensitivity Index (WBISI), Insulinogenic Index (IGI); ß-cell demand index (BCDI) and Insulin Secretion-Sensitivity Index 2 (ISSI-2) were longitudinally estimated during the oral glucose tolerance test. RESULTS: After a median follow-up of 2.23 (1-4.52) y, obese patients showed significant decrease in WBISI (p<0.0001), and increase in fasting (p = 0.005) and 2 h glucose (2HG, p = 0.001). One child in preschool age and 4 school age children presented with 2HG between 7.8-11.1 mmol/l. Best predictors of WBISI, 2HG and BCDI in the school age were changes in BMI z-score (R(2) = 0.309; p = 0.002; ß = -0.556), ISSI-2 (R(2) = 0.465; p<0.0001; ß = -0.682), and BMI z-score (R(2) = 0.246; p = 0.008; 0.496), respectively. CONCLUSIONS: In morbidly obese children, insulin sensitivity seems to decline even before pubertal transition, but changes in total adiposity can only partially explain this variation.

Beyond the morphology of the glucose curve following an oral glucose tolerance test in obese youth.

BACKGROUND: To describe the morphology of glucose curve during the oral glucose tolerance test (OGTT) and any association with glucose tolerance, insulin action and secretion in obese youth. STUDY DESIGN: Cross-sectional. METHODS: OGTT data of 553 patients were analysed. Subjects were divided in groups based on the morphology (i.e. monophasic, biphasic, triphasic and upward monotonous) of glucose curve. Insulin action was estimated by the homeostasis model assessment of insulin resistance, the insulin sensitivity, the muscle insulin sensitivity and the hepatic insulin resistance indexes (HIRI), and the oral glucose insulin sensitivity (OGIS). Insulin secretion was estimated by the insulinogenic index (IGI). Disposition index, including the insulin secretion-sensitivity index-2, and areas under glucose (AUC(G)) and insulin (AUC(I)) curves were computed. RESULTS: In patients with normal glucose tolerance (n=522), prevalent morphology of the glucose curve was monophasic (n=285, 54%). Monophasic morphology was associated with the highest concentration of 1 h plasma glucose (P<0.0001) and AUC(G) (P<0.0001); biphasic morphology with better insulin sensitivity as estimated by OGIS (P<0.03) and lower AUC(I) (P<0.0001); triphasic morphology with the highest values of HIRI (P<0.02) and IGI (P<0.007). By combining morphologies of glucose and insulin curves or time of the glucose peak, a deeper characterisation of different phenotypes of glucose metabolism emerged. CONCLUSIONS: Morphologies of the glucose curve seem reflecting different metabolic phenotypes of insulin action and secretion, particularly when combined with morphologies of insulin curve or time of glucose peak. Such findings may deserve validation in cohort study, in which glucose metabolism would be estimated by using gold standard techniques.