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


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.
Division of Weight Management and Wellness, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. fbacha@bcm.edu
Fida
F
Bacha
Neslihan
N
Gungor
Sojung
S
Lee
Silva A
SA
Arslanian
D015502:Absorptiometry, Photon; D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology*; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D056128:Obesity, Abdominal / Q000150:complications / Q000503:physiopathology*
D001786:Blood Glucose; D006442:Glycated Hemoglobin