High prevalence of prediabetes in a Swedish cohort of severely obese children.

OBJECTIVE: In this cohort of severely obese children and adolescents in Sweden we investigate the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance, (IGT) and silent type 2 diabetes (T2D), in relation to insulin resistance, insulin secretion, disposition index and cardio respiratory fitness. METHODS: A total of 134 obese children and adolescents [57 females, 77 males, age 13.7 ± 2.7, body mass index (BMI) standard deviation score (SDS) 3.6 ± 0.6] consecutively referred to the National Childhood Obesity Centre performed an oral glucose tolerance test (OGTT), frequently sampled intravenous glucose tolerance test (fs-IVGTT), dual X-ray absorptiometry (DEXA), bicycle ergometer test and fasting levels of glucose, insulin and c-peptide were obtained and homeostatic model of insulin resistance (HOMA-IR) was calculated. RESULTS: Isolated impaired fasting glucose (i-IFG) were present in 35.8 and 6% had isolated IGT. Combined IGT and IFG were present in 14.2%. The subjects with combined IGT/IFG had significantly lower acute insulin response (AIR) compared with subjects who had normal glucose metabolism or i-IFG (p < 0.05). Among the prepubertal children (n = 24), 25% (6/24) had i-IFG and 25% (6/24) had IGT/IFG and it was predominantly males. Disposition index was the major determinant of 2-h glucose levels (ß = -0.49, p = 0.0126). No silent diabetes was detected. CONCLUSION: In this cohort of severely obese children and adolescents the prevalence of prediabetes was very high. IFG was two times higher in this cohort of severely obese children than in a recently published unselected cohort of obese children in Sweden. In spite of the high prevalence of prediabetes, no subjects with silent diabetes were found.

HOMA-IR and QUICKI: decide on a general standard instead of making further comparisons.

AIM: To limit further comparisons between the two fasting indices Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI), and to examine their robustness in assessing insulin sensitivity. METHODS: A total of 191 obese children and adolescents (age 13.9 ± 2.9 years, BMI SDS 6.1 ± 1.6), who had undergone a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT), were included. Receiver operating characteristic curve (ROC) analysis was used to compare indices in detecting insulin resistance and Bland-Altman plots to investigate agreement between three consecutive fasting samples when compared to using single samples. RESULTS: ROC analysis showed that the diagnostic accuracy was identical for QUICKI and HOMA-IR [area under the curve (AUC) boys 0.80, 95%CI 0.70-0.89; girls 0.80, 0.71-0.88], while insulin had a nonsignificantly lower AUC (boys 0.76, 0.66-0.87; girls 0.75, 0.66-0.84). Glucose did not perform better than chance as a diagnostic test (boys 0.47, 0.34-0.60; girls 0.57, 0.46-0.68). Indices varied with consecutive sampling, mainly attributable to fasting insulin variations (mean maximum difference in HOMA-IR -0.8; -0.9 to -0.7). CONCLUSIONS: Using both HOMA-IR and QUICKI in further studies is superfluous as these indices function equally well as predictors of the FSIVGTT sensitivity index. Focus should be on establishing a general standard for research and clinical purposes.

Adiposity measures as indicators of metabolic risk factors in adolescents.

AIM: To examine the relation between adiposity assessment methods (percentage body fat (%BF), BMI, and waist circumference (WC)) and individual metabolic risk factors (f-insulin, HDL cholesterol, triglycerides) and a combined measure of metabolic risk. METHODS: Crosssectional study of 300 males (BMI 20.8 +/- 3.0 kg/m(2)) and females (BMI 21.3 +/- 2.9 kg/m(2)) 17 years of age. F-insulin and components of the metabolic syndrome defined by the International Diabetes Federation (IDF) were used as metabolic risk indicators, with samples stratified into BMI, %BF, and WC groups, respectively. Diagnostic accuracy was expressed as the area under the ROC curve (AUC). RESULTS: In males, diagnostic accuracy for HDL and f-insulin was poor to fair for BMI (AUC 0.70, p = 0.001; 0.60, p = 0.22), WC (0.68, p = 0.003; 0.63, p = 0.11), and %BF (0.65, p = 0.009; 0.66, p = 0.04). The diagnostic accuracy for triglycerides was greater for all three measures (BMI 0.92, WC 0.95, %BF 0.87; all p < 0.001). For females, neither test performed better than chance for f-insulin and HDL, and only %BF performed better than chance for triglycerides (0.65, p = 0.08). All three measures exhibited higher accuracy for presence of > or =2 metabolic risk factors (AUCs 0.76-0.91, p < 0.001) in both sexes. CONCLUSION: %BF was not superior to BMI and WC for detecting metabolic risk in the general adolescent population.

Alternative methods of insulin sensitivity assessment in obese children and adolescents.

OBJECTIVE: To validate fasting indexes against minimal model analysis (MMOD) of the frequently sampled intravenous glucose tolerance test (FSIVGTT) in an obese pediatric population. RESEARCH DESIGN AND METHODS: FSIVGTT-MMOD results were compared with homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin with the sample stratified by sex, puberty, and sensitivity index (S(i)) median in 191 children (82 males and 109 females, 13.9 +/- 2.9 years of age, BMI 36.9 +/- 6.2 kg/m(2), BMI SD score 6.1 +/- 1.6). RESULTS: Across pubertal groups, correlation coefficients between S(i) and HOMA-IR ranged from -0.43 to -0.78 in males and from -0.53 to -0.57 in females (age and BMI adjusted, P < 0.05 in all instances). Similar results were seen for fasting insulin. In females, the relationship was significantly weaker in more-insulin-resistant subjects. CONCLUSIONS: The validity of fasting indexes in explaining S(i) was sex dependent, varied with pubertal stage, and in females was influenced by degree of insulin sensitivity. In obese pediatric populations, we generally discourage the use of fasting indexes, although the validity varies within subgroups.

Transthyretin constitutes a functional component in pancreatic beta-cell stimulus-secretion coupling.

Transthyretin (TTR) is a transport protein for thyroxine and, in association with retinol-binding protein, for retinol, mainly existing as a tetramer in vivo. We now demonstrate that TTR tetramer has a positive role in pancreatic beta-cell stimulus-secretion coupling. TTR promoted glucose-induced increases in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) and insulin release. This resulted from a direct effect on glucose-induced electrical activity and voltage-gated Ca(2+) channels. TTR also protected against beta-cell apoptosis. The concentration of TTR tetramer was decreased, whereas that of a monomeric form was increased in sera from patients with type 1 diabetes. The monomer was without effect on glucose-induced insulin release and apoptosis. Thus, TTR tetramer constitutes a component in normal beta-cell function. Conversion of TTR tetramer to monomer may be involved in the development of beta-cell failure/destruction in type 1 diabetes.