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

¹Departments of Preventive Medicine, Physiology, Biophysics, and Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California 90033

Objective: To examine changes in risk factors in overweight and obese Hispanic children at high risk of developing type 2 diabetes (T2D).

Research Design & Methods: 128 overweight/obese Hispanic children with a family history of T2D were recruited primarily from clinics in East Los Angeles. Children were evaluated annually for 4 years with an oral glucose tolerance test, applying ADA criteria to define diabetes and pre-diabetes (PD). Insulin sensitivity (S_i), the acute insulin response to glucose (AIR) and beta-cell function (BCF) were determined from frequently sampled intravenous glucose tolerance tests, total body fat by DEXA and intra-abdominal and subcutaneous abdominal adipose tissue (IAAT and SAAT) by MRI were assessed in years 1, 2 and 4.

Results: None subjects developed T2D, 40% never had PD, 47% had intermittent PD with no clear pattern over time, and 13% had persistent PD. At baseline, those with persistent PD had lower BCF, and higher IAAT. In repeated measures, S_i deteriorated regardless of PD, and there was a significant effect of PD on AIR (42% lower in PD; p=0.01) and DI (34% lower in PD; p=0.021) and a significant interaction of PD*time on IAAT (greater increase over time in those with PD; p=0.034).

Conclusions: In this group of Hispanic children at high risk of type 2 diabetes: a) pre-diabetes is highly variable from year to year; b) the prevalence of persistent pre-diabetes over 3 years is 13%; and, c) children with persistent pre-diabetes have lower beta-cell function, due to a lower acute insulin response, and increasing visceral fat over time.

Key Words: impaired glucose tolerance • pre-diabetes • visceral fat • beta-cell function • insulin sensitivity • obesity • type 2 diabetes

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