Vered Lewy

Insulin resistance of puberty in African-American children: lack of a compensatory increase in insulin secretion

Abtract: Type 2 diabetes has been increasing in children, mostly affecting minority populations at around the age of puberty. Despite a multitude of studies demonstrating pubertal insulin resistance/hyperinsulinemia in white children, data are almost non‐existent in African‐American children. The aim of the present study was to investigate the impact of puberty on glucose metabolism, insulin sensitivity and secretion in African‐American children. Twenty prepubertal and 16 pubertal African‐American subjects participated. All underwent a 3‐h hyperinsulinemic (40 mU/m2/min) euglycemic clamp to determine insulin‐stimulated glucose disposal, and a 2‐h hyperglycemic (12.5 mmol/L) clamp to assess first‐ and second‐phase insulin secretion. Body composition was assessed by dual energy X‐ray absorptiometry (DEXA) and visceral and subcutaneous abdominal adiposity with computed tomography (CT) scan at L4–L5. Total glucose disposal, glucose oxidation and non‐oxidative glucose disposal were significantly lower in the pubertal group compared with the prepubertal one (53.8 ± 3.9 vs. 72.2 ± 5.0 µmol/kg/min, p = 0.009; 23.3 ± 1.1 vs. 31.6 ± 1.7 µmol/kg/min, p = 0.001; and 30.0 ± 3.3 vs. 40.5 ± 3.9 µmol/kg/min, p = 0.049, respectively). Insulin sensitivity was ∼30% lower in the adolescents compared with the prepubertal children. However, first‐ and second‐phase insulin secretions were not different between the two groups (971.4 ± 180.6 vs. 1044.0 ± 191.4 pmol/L and 999.6 ± 159.6 vs. 955.8 ± 142.2 pmol/L, respectively). In conclusion, despite ∼30% lower insulin sensitivity in African‐American adolescents compared with prepubertal children, insulin secretion is not higher. This is in contrast to published findings in white children in whom insulin secretion is higher during puberty. These racial differences in physiologic adaptation to puberty could play a role in the higher prevalence of type 2 diabetes in African‐American children at the time of puberty.

No association between body mass index and β3-adrenergic receptor variant (W64R) in children with premature pubarche and adolescent girls with hyperandrogenism ☆

OBJECTIVE To determine if the Trp(64)Arg (W64R) variant of the beta(3)-adrenergic receptor (ADRB3) could be used as a genetic marker to define risk for polycystic ovary syndrom (PCOS) and/or obesity in children and adolescents. DESIGN Association study. SETTING Academic research environment. PATIENT(S) Children referred for evaluation of premature pubic hair (n = 63), adolescent girls referred for evaluation of hirsutism and/or oligomenorrhea (n = 33), and healthy adult controls (n = 67). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Relationship of body mass index (BMI) to presence or absence of W64R variant and frequency of W64R variant in our patient population. RESULT(S) Body mass index (kg/m(2)) was determined for 63 children (55 girls and 8 boys) and 33 adolescent girls. Presence or absence of the W64R variant was assayed by polymerase chain reaction (PCR) amplification followed by allele-specific restriction fragment digest. Twelve subjects and 11 healthy controls were found to be heterozygous for the W64R variant. One subject was found to be homozygous for the W64R variant. Allele frequency for the W64R variant was comparable between patients and controls. Among the patients, mean BMI values were not different between carriers and noncarriers. CONCLUSION(S) Although other studies suggest that the W64R variant is associated with the development of obesity and insulin resistance, we cannot demonstrate that it has a major effect on BMI in children with premature pubarche or in adolescent girls with hyperandrogenism. Serial observations are necessary to determine if this variant predicts the development of obesity and/or PCOS in adulthood.

Insulin Sensitivity in African-American Children with and without Family History of Type 2 Diabetes

OBJECTIVE African-Americans are at increased risk for type 2 diabetes. We have previously demonstrated that African-American children are hyperinsulinemic and insulin resistant compared with their white American peers. The aim of the present investigation was to assess the impact of family history of type 2 diabetes on insulin sensitivity in African-American children. RESEARCH DESIGN AND METHODS A total of 13 prepubertal healthy children with negative family history (FH-) and 9 with positive family history (FH+) of type 2 diabetes underwent a 3-h hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp study to assess insulin sensitivity. The groups were comparable for age, pubertal status, total body adiposity determined by dual-energy X-ray absorptiometry, abdominal adiposity assessed by computed tomography scan at the level of L4-5 lumbar vertebra, and physical fitness measured by maximal oxygen consumption (VO2max). RESULTS The FH+, compared with the FH-, group had lower insulin-stimulated glucose disposal (10.9+/-1.2 vs. 14.2+/-0.9 mg x kg(-1) x min(-1), P = 0.035) and lower nonoxidative glucose disposal (5.7+/-0.8 vs. 8.3+/-0.6 mg x kg(-1) x min(-1), P = 0.015), with no differences in rates of glucose oxidation, fat oxidation, or insulin-mediated free fatty acid suppression. Fasting hepatic glucose production assessed with [6,6-2H2]glucose and basal rates of glucose and fat oxidation were not different between the two groups. CONCLUSIONS These data suggest that in African-American children, family history of type 2 diabetes is a risk factor for insulin resistance. These children manifest important metabolic alterations, including impaired insulin-stimulated total and nonoxidative glucose disposal early in the first decade of life. We propose that this familial tendency, combined with environmental influences, could lead to type 2 diabetes decades later.

Sex Hormone Binding Globulin (SHBG) and Insulin-Like Growth Factor Binding Protein-1 (IGF-BP1) in Children with Acanthosis Nigricans: A Marker for Insulin Resistance and/or Hyperinsulinemia? † 452

Sex Hormone Binding Globulin (SHBG) and Insulin-Like Growth Factor Binding Protein-1 (IGF-BP1) in Children with Acanthosis Nigricans: A Marker for Insulin Resistance and/or Hyperinsulinemia? † 452

Central Adiposity and Insulin Sensitivity in Healthy African-American Children |[bull]| 411

Abdominal adiposity has been implicated as a risk factor for insulin resistance and NIDDM in adults. African-Americans (AA) are at increased risk for obesity, CVD, hypertension and NIDDM. We have shown that healthy AA children are insulin resistant and have higher insulin secretion compared with their White peers (J Pediatr 129:1996; J Clin Endocrinol Metab 82:1997). Moreover, AA children are more obese with central distribution of fat compared with their White peers. Therefore, the aim of the present investigation was to study the relationship of central obesity to insulin resistance in AA children. We studied 19 (10M, 9F) healthy AA prepubertal children, age (9.8±0.2 yrs), BMI (19.6±1.0 kg/m2). Body composition was assessed with DEXA, and abdominal adiposity by CT scan at the level of L4-5with measurements of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). Insulin action was assessed by a 3hr hyperinsulinemic (40mu/m2/min)-euglycemic clamp. Insulin stimulated glucose disposal (Rd) was calculated over the last 30 min of the clamp. Results: (mean ± SEM) However, in a multiple regression analysis SAT was the only significant determinant of Rd explaining 64% of its variability independent of%BF. Table