Persistence of Pre-Diabetes in Overweight and Obese Hispanic Children : Association With Progressive Insulin Resistance, Poor β-Cell Function, and Increasing Visceral Fat

OBJECTIVE—To examine changes in risk factors in overweight and obese Hispanic children at high risk of developing type 2 diabetes. RESEARCH DESIGN AND METHODS—We recruited 128 overweight/obese Hispanic children with a family history of type 2 diabetes primarily from clinics in East Los Angeles. Children were evaluated annually for 4 years with an oral glucose tolerance test, applying American Diabetes Association criteria to define diabetes and pre-diabetes. Insulin sensitivity (S(i)), acute insulin response (AIR) to glucose, and β-cell function (BCF) were determined from frequently sampled intravenous glucose tolerance tests, and total body fat by dual-energy X-ray absorptiometry and intra-abdominal and subcutaneous abdominal adipose tissue (IAAT and SAAT) by magnetic resonance imaging were assessed in years 1, 2, and 4. RESULTS—No subjects developed type 2 diabetes, 40% never had pre-diabetes, 47% had intermittent pre-diabetes with no clear pattern over time, and 13% had persistent pre-diabetes. At baseline, those with persistent pre-diabetes had lower BCF and higher IAAT. In repeated measures, S(i) deteriorated regardless of pre-diabetes, and there was a significant effect of pre-diabetes on AIR (42% lower in pre-diabetes; P = 0.01) and disposition index (34% lower in pre-diabetes; P = 0.021) and a significant interaction of pre-diabetes and time on IAAT (greater increase over time in those with pre-diabetes; P = 0.034). CONCLUSIONS—In this group of Hispanic children at high risk of type 2 diabetes, 1) pre-diabetes is highly variable from year to year; 2) the prevalence of persistent pre-diabetes over 3 years is 13%; and 3) children with persistent pre-diabetes have lower BCF, due to a lower AIR, and increasing visceral fat over time.