Impaired Glucose Tolerance and Reduced β-Cell Function in Overweight Latino Children with a Positive Family History for Type 2 Diabetes

Abstract

The objective of this study was to examine relationships between impaired glucose tolerance (IGT) and body composition and insulin-related phenotypes in 150 overweight Latino children with a family history of type 2 diabetes. Glucose tolerance was assessed by an oral glucose challenge. Body composition was assessed by dual energy x-ray absorptiometry and magnetic resonance imaging. Insulin sensitivity, the acute insulin response, and the disposition index (DI), as an index of beta-cell function, were determined by an iv glucose tolerance test and compared between normal glucose-tolerant and IGT children. IGT was present in 28% of children, and was similar across obesity groups, but higher in children exposed to gestational diabetes mellitus (41% IGT). There were no significant differences in body composition, fat distribution, insulin sensitivity, or acute insulin response, but DI was significantly lower in IGT children by 16% (P < 0.02), and DI was inversely related to age. In conclusion, IGT is present in 28% of overweight Latino children with a family history of type 2 diabetes, is not influenced by obesity, is more prevalent in children exposed to gestational diabetes mellitus, and is related to poor beta-cell function, which shows signs of deterioration with age in this population.

Insulin sensitivity, insulin secretion and β-cell function during puberty in overweight Hispanic children with a family history of type 2 diabetes

“…Tanner stage was assessed by a physician according to the wellestablished criteria of Marshall and Tanner. 16,17 Consistent with our earlier reports, [9][10][11][12][13] Tanner stage was expressed based upon breast development in girls and pubic hair growth in boys, those aspects of pubertal development that reflect the biological activity of gonadal steroid exposure in each sex (testosterone in boys and estrogen in girls). Gonadal steroids were not measured in this study.…”

“…Findings from this investigation have been published previously. [9][10][11][12][13] Participants met the following inclusion criteria at their initial visit: age-and gender-specific BMI Z85th percentile; 14 Hispanic background (all four grandparents of Hispanic descent); 8-13-y old; family history of type 2 diabetes (sibling, parent, or grandparent) and absence of diabetes evaluated through an oral glucose tolerance test (OGTT). 15 Participants were neither currently taking any medication(s) nor carried a previous clinical diagnosis known to influence body composition, insulin sensitivity, insulin secretion, diet or physical activity.…”

“…32 The progressive loss of b-cell function is thought to precede the development of IGT and type 2 diabetes 33 and DI is an important feature distinguishing overweight Hispanic youth with and without IGT. 12 Longitudinal analyses will be required for supportive evidence, but if SI remains low in these children as they mature (a likely scenario given their high fat mass), insulin secretion must remain elevated to help maintain normoglycemia. Over time, the increased secretory demands associated with prolonged insulin resistance may not be sustainable.…”

Prevalence of type 2 diabetes among women with a previous history of gestational diabetes mellitus

“…However, the product of insulin sensitivity and the acute insulin response, an index of b-cell compensation in response to insulin sensitivity termed the disposition index (DI), is more familial than first-phase insulin secretion or insulin sensitivity alone [28]. The DI is significantly lower in subjects with a family history of T2DM [29][30][31][32] than in controls. These studies support the notion that individuals with a family history of T2DM have an underlying genetic defect that renders them susceptible to this disease.…”

Cardiovascular fitness and physical activity in children with and without impaired glucose tolerance

“…Recent data suggest that nearly 30% of overweight children have IGT. [2][3][4] In adults, IGT is thought to be an intermediate stage in the pathogenesis of type 2 diabetes. 5 Although the predictive value of IGT in children is yet to be established, cross-sectional evidence indicates that early signs of b-cell insufficiency suggest a higher risk for the development of type 2 diabetes in these youth.…”