Rola Saad

Progression from normal glucose tolerance to type 2 diabetes in a young girl: longitudinal changes in insulin sensitivity and secretion assessed by the clamp technique and surrogate estimates

Abstract:  The pathophysiology of type 2 diabetes (T2DM) involves insulin resistance and relative insulin deficiency in at‐risk youth. We‐report longitudinal changes in insulin sensitivity and secretion in a high‐risk African‐American youth with obesity and polycystic ovary syndrome who progressed from normal glucose tolerance to impaired glucose tolerance to T2DM within 5 yr. This report demonstrates that in our patient: (i) insulin resistance was the pre‐existing abnormality, but it was the marked decline in insulin secretion which led to T2DM and (ii) surrogate estimates of insulin sensitivity using fasting glucose and insulin concentrations were not reliable indices in reflecting the changes in in vivo insulin sensitivity in this case.

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.

Does adiponectin explain the lower insulin sensitivity and hyperinsulinemia of African-American children?

Abstract:  Adiponectin is an adipocytokine with antidiabetogenic properties. The present study investigated: (i) the effect of race on adiponectin levels and (ii) the relationship of adiponectin levels in children to insulin sensitivity and secretion. Fasting adiponectin levels were determined in 22 healthy prepubertal black compared with 22 white children of similar body composition. We previously reported these black children to have lower insulin sensitivity and higher first‐phase insulin secretion than their white peers. Fasting adiponectin levels were lower in black children (9.9 ± 1.0 µg/mL vs. 15.7 ± 1.1 µg/mL, p < 0.001). Adiponectin correlated positively with insulin 
sensitivity (r = 0.29, p = 0.06) and negatively with first‐phase insulin levels (r = −0.47, p = 0.001). In a multiple regression analysis, 48% of the variance in first‐phase insulin secretion was explained by the independent effects of race (p = 0.017), adiponectin (p = 0.03), and percentage of body fat (p < 0.001). Adiponectin did not contribute significantly to the variance in insulin sensitivity. In summary, black children have approximately 35% lower adiponectin levels than their white peers. Lower adiponectin does not seem to explain the racial differences in insulin sensitivity. The relationship of hyperinsulinemia and hypoadiponectinemia needs to be further explored.