Pathogenic factors of glucose intolerance in obese Japanese adolescents with type 2 diabetes.
We attempted to identify the pathogenic factors involved in the progression to type 2 diabetes in obese Japanese adolescents. Subjects included 18 nondiabetic obese adolescents, 12 obese adolescents with type 2 diabetes on diet therapy, 10 obese adolescents with type 2 diabetes manifesting ketosis at onset or with a history of treatment with hypoglycemic agents, and 26 non-obese adolescent control subjects. The first-phase insulin response (FPIR), glucose disappearance constant (Kg), glucose effectiveness (Sg), and insulin sensitivity (S(I)) were obtained using an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT) and a minimal model analysis. The disposition index (DI, by FPIR x S(I)) was determined to assess any endogenous insulin effect. The results showed that Kg was decreased significantly (P = .0006) with the progression to severe diabetes in the obese groups. Although S(I) and Sg did not differ significantly among the 3 obese groups, both parameters were significantly lower in each obese group versus the non-obese controls. As a result of the significant decrease in FPIR (P < .0001), the DI decreased (P = .0006) with the progression to severe diabetes in the obese groups. In conclusion, an early manifestation of type 2 diabetes with occasional ketosis at onset may result from beta-cell dysfunction to glucose stimulation. This finding is demonstrated by the relatively low FPIR to decreased S(I) in obese Japanese adolescents, as well as the low Sg as a synergic role in glucose intolerance. The present findings from a Japanese population for pathogenic factors aside from obesity may help us to gain a better understanding of the progression to adolescent, early-onset, obese type 2 diabetes and its severity.
Kobayashi
K
K
Department of Pediatrics, Yamanashi Medical University, Nakakoma-gun, Japan.
Amemiya
S
S
Higashida
K
K
Ishihara
T
T
Sawanobori
E
E
Kobayashi
K
K
Mochizuki
M
M
Kikuchi
N
N
Tokuyama
K
K
Nakazawa
S
S
D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008954:Models, Biological; D009765:Obesity
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin