Progressive deterioration of β-cell function in obese youth with type 2 diabetes

Pediatr Diabetes. 2013 Mar;14(2):106-11. doi: 10.1111/j.1399-5448.2012.00915.x. Epub 2012 Aug 23.

Abstract

Objective: In adults, type 2 diabetes (T2DM) is characterized with progressive deterioration in insulin secretion. Data are scanty in youth. We investigated prospectively the change in β-cell function and in insulin sensitivity in youth with T2DM.

Research design and methods: Six adolescents with T2DM [hemoglobin A1c (HbA1c) 6.6 ± 1.0%] underwent evaluation of hepatic glucose production (HGP; [6,6-²H₂] glucose), insulin-stimulated glucose disposal (Rd; hyperinsulinemic-euglycemic clamp), first- and second-phase insulin/C-peptide secretion (hyperglycemic clamp), body composition dual energy X-ray absorptiometry (DEXA), and abdominal adiposity (computed tomography) within 3 yr of the diagnosis of diabetes and after 12-16 months of follow-up.

Results: Weight, body mass index (37.1 ± 6.9), HbA1c (6.3 ± 0.7%), HGP (2.8 ± 1.2 mg/kg/min), and Rd (4.9 ± 3.4 mg/kg/min) did not change significantly from baseline. However, first-phase insulin and C-peptide declined (152.6 ± 261.2 vs. 75.9 ± 108.5 μU/mL, p = 0.028; 8.0 ± 6.3 vs. 5.9 ± 4.4 ng/mL, p = 0.048, respectively) with no significant change in second-phase insulin/C-peptide. The rate of decline in β-cell function was ∼20% per year.

Conclusions: After a median duration of 20 months of diabetes, youth with T2DM manifest a rapid decline in β-cell function with no significant changes in peripheral or hepatic insulin sensitivity. Interventions to retard this deterioration in β-cell function should be investigated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Blood Glucose / metabolism
  • Body Composition
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Glucose Clamp Technique
  • Glycated Hemoglobin A
  • Humans
  • Insulin Resistance / physiology
  • Insulin-Secreting Cells / physiology*
  • Male
  • Obesity, Abdominal / complications
  • Obesity, Abdominal / physiopathology*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A