Proinsulin in girls: relationship to obesity, hyperinsulinemia, and puberty.
In adults with impaired glucose tolerance (IGT) and obesity (OB), an elevated proinsulin (PI) is predictive of type 2 diabetes mellitus (DM) and precedes the diagnosis by 5-20 yr. In type 2 DM, the PI is disproportionately elevated, i.e. increased PI/insulin ratio (PI/I). Few studies have evaluated PI in children at risk for type 2 DM. In the face of the current epidemic, we evaluated the relationship of PI and PI/I to IGT, insulin resistance (IR) defined by homeostasis model of assessment (HOMA), degree of OB, and stage of puberty in 70 girls (mean age 10.8 yr; body mass index z-score 3.5; ethnicity 64% Hispanic, 19% white, 16% African-American, and 1% other). Family history of DM was reported in 83%, and acanthosis nigricans was present in 80%. Subjects underwent a 2-h oral glucose tolerance test with glucose, insulin, and PI determinations every 30 min. All had normal hemoglobin A1c and fasting glucose. Five had IGT. With higher HOMA-IR, PI increased (P < 0.05), yet the ratio of fasting PI/I was lower (P < 0.05). Girls with body mass index z-score greater than 4 (n = 29) had higher PI than nonobese girls (n = 19, P < 0.05), but PI/I ratios were not different. PI-0 was increased in late puberty (n = 29), compared with prepuberty (n = 26, P < 0.05), but PI/I ratios showed no statistical difference. We found PI increased with increasing IR and OB in girls. Overall, PI/I was not different, suggesting the elevated PI reflects increased beta-cell output proportional to the elevated insulin in these groups and not a defect in PI processing or secretion. In fact, the lower fasting PI/I of the highest HOMA-IR quartile vs. the lowest HOMA quartile indicates more efficient conversion of PI to I in the presence of increasing IR in these girls.
D000293:Adolescent; D044383:Black People; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006630:Hispanic or Latino; D006706:Homeostasis; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000378:metabolism; D009765:Obesity / Q000097:blood*; D011384:Proinsulin / Q000097:blood*; D011627:Puberty; D012307:Risk Factors; D044465:White People; D001741:Black or African American
D011384:Proinsulin