Impaired beta-cell sensitivity to glucose and maximal insulin secretory capacity in adolescents with type 2 diabetes.
BACKGROUND
Adults with type 2 diabetes mellitus (T2DM) have broad impairments in beta-cell function, including severe attenuation of the first-phase insulin response to glucose, and reduced beta-cell mass. In adolescents with T2DM, there is some evidence that beta-cell dysfunction may be less severe. Our objective was to determine beta-cell sensitivity to glucose and maximal insulin secretory capacity (AIR(max)) in teenagers with T2DM.


METHODS
Fifteen adolescents with T2DM [11 F/4 M, age 18.4 +/- 0.3 yr, body mass index (BMI) 39.8 +/- 2.2 kg/m(2)] and 10 non-diabetic control subjects (7 F/3 M, age 17.4 +/- 0.5 yr, BMI 41.5 +/- 2.2 kg/m(2)) were studied. T2DM subjects had a mean duration of diabetes of 48.8 +/- 6.4 months, were treated with conventional therapies, and had good metabolic control [hemoglobin A1c (HbA1c) 6.7 +/- 1.2%]. Insulin and C-peptide were determined before and after a graded glucose infusion and after intravenous arginine at a whole blood glucose level of >or=22 mM.


RESULTS
The insulin response to increasing plasma glucose concentrations was blunted in the diabetic compared with control subjects (34.8 +/- 11.9 vs. 280.5 +/- 57.8 pmol/mmol; p < 0.0001), and AIR(max) was also significantly reduced in the diabetic group (1868 +/- 330 vs. 4445 +/- 606; p = 0.0005).


CONCLUSIONS
Even adolescents with well-controlled T2DM have severe impairments of insulin secretion. These data support beta-cell dysfunction as central in the pathogenesis of T2DM in young people, and indicate that these abnormalities can develop over a period of just several years.
Elder
Deborah A
DA
Cincinnati Children's Hospital Medical Center, Department of Pediatrics, Division of Endocrinology, Cincinnati, OH 45229, USA. deborah.elder@cchmc.org
Woo
Jessica G
JG
D'Alessio
David A
DA
D000293:Adolescent; D001120:Arginine / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005215:Fasting / Q000502:physiology; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male
D001120:Arginine; D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human