Pathogenic factors of glucose intolerance in obese Japanese adolescents with type 2 diabetes

Kobayashi, Koji; Amemiya, Shin; Higashida, Kosuke; Ishihara, Tsukasa; Sawanobori, Emi; Kobayashi, Kenichi; Mochizuki, M.; Kikuchi, Nobuyuki; Tokuyama, Kunpie; Nakazawa, Shinpei

doi:10.1016/s0026-0495(00)91221-6

Cited by 52 publications

(35 citation statements)

References 32 publications

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“…In a recent investigation of nondiabetic youth, we demonstrated that hypoadiponectinemia is a strong and independent correlate of insulin resistance (7). Our findings with respect to lower FPIS and GDI in adolescents with type 2 diabetes are in agreement with the Japanese study in adolescents (14).…”

Section: Correlationssupporting

confidence: 92%

“…A Japanese study (14) using the frequently sampled intravenous glucose tolerance test revealed that obese nondiabetic adolescents and obese adolescents with type 2 diabetes were equally insulin resistant. This is in contrast to our findings of ϳ50% lower insulin sensitivity in the type 2 diabetic group compared with obese control subjects.…”

Section: Correlationsmentioning

confidence: 99%

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Youth Type 2 Diabetes

et al. 2005

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OBJECTIVE -This study evaluates insulin sensitivity, pancreatic ␤-cell function (BCF), and the balance between the two in youth with type 2 diabetes and assesses the relationship of diabetes duration and HbA 1c to insulin sensitivity and BCF.RESEARCH DESIGN AND METHODS -The subjects were 14 adolescents with type 2 diabetes and 20 obese control subjects of comparable age, BMI, body composition, and puberty. Insulin sensitivity was evaluated with a 3-h hyperinsulinemic (80 mU ⅐ m -2 ⅐ min -1 ) euglycemic clamp. First-phase insulin secretion (FPIS) and second-phase insulin secretion (SPIS) were evaluated with a 2-h hyperglycemic (12.5 mmol/l) clamp. Fasting glucose rate of appearance was determined with the use of [6,6-2 H 2 ]glucose.RESULTS -Fasting glucose rate of appearance was higher in type 2 diabetic patients than in obese control subjects (16.5 Ϯ 1.1 vs. 12.3 Ϯ 0.5 mol ⅐ kg -1 ⅐ min -1 ; P ϭ 0.002). Insulin sensitivity was lower in type 2 diabetic patients than in obese control subjects (1.0 Ϯ 0.1 vs. 2.0 Ϯ 0.2 mol ⅐ kg -1 ⅐ min -1 per pmol/l; P ϭ 0.001). Fasting insulin was higher in type 2 diabetic patients than in obese control subjects (289.8 Ϯ 24.6 vs. 220.2 Ϯ 18.0 pmol/l; P ϭ 0.007), and FPIS and SPIS were lower (FPIS: 357.6 Ϯ 42.0 vs. 1,365.0 Ϯ 111.0 pmol/l; SPIS: 652.2 Ϯ 88.8 vs. 1,376.4 Ϯ 88.8 pmol/l; P Ͻ 0.001 for both). The glucose disposition index (GDI ϭ insulin sensitivity ϫ FPIS) was ϳ86% lower in type 2 diabetic patients than in obese control subjects. HbA 1c correlated with FPIS (r ϭ Ϫ0.61, P ϭ 0.025) with no relationship to insulin sensitivity.CONCLUSIONS -Despite the impairment in both insulin sensitivity and BCF in youth with type 2 diabetes, the magnitude of the derangement is greater in BCF than insulin sensitivity when compared with that in obese control subjects. The inverse relationship between BCF and HbA 1c may either reflect the impact of deteriorating BCF on glycemic control or be a manifestation of a glucotoxic phenomenon on BCF. Future studies in youth type 2 diabetes should target the natural course of ␤-cell failure and means of retarding and/or preventing it. Diabetes Care 28:638 -644, 2005D espite the increasing rate of type 2 diabetes in youth, the information on its pathophysiology is mostly derived from adult studies (1). Decreased insulin sensitivity and impaired ␤-cell function (BCF) are the two key components in type 2 diabetes pathogenesis (2-4). The development sequence of these abnormalities has been long debated. Several studies in adults proposed that insulin resistance with compensatory hyperinsulinemia is the initial step in type 2 diabetes pathogenesis (2,4). This is an implication of the hyperbolic relationship between insulin sensitivity and BCF, which calls for an increase in insulin secretion when insulin sensitivity decreases (4). The subsequent step in type 2 diabetes pathogenesis is impaired early insulin secretion, leading to postprandial and, later, fasting hyperglycemia (at which time clinical diabetes becomes evident). This sequence has also been do...

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Section: Correlationssupporting

confidence: 92%

Section: Correlationsmentioning

confidence: 99%

Youth Type 2 Diabetes

et al. 2005

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“…Studies investigating the pathophysiology of youth type 2 diabetes are very limited and have conflicting results (3)(4)(5)(6)26). In one of the earliest studies, first-phase insulin response during a frequently sampled intravenous glucose tolerance test was lower in type 2 diabetic patients compared with obese control subjects with no difference in insulin sensitivity (3).…”

Section: Discussionmentioning

confidence: 99%

“…Diabetes in humans is classified into two main types: type 1 diabetes, where the pathophysiology is autoimmune destruction of the pancreatic ␤-cells; and type 2 diabetes, where insulin resistance is central to the disease process together with a nonimmune-mediated ␤-cell failure relative to insulin resistance (2). Limited data in the pediatric literature suggest that the pathophysiology of youth type 2 diabetes is a combination of severe insulin resistance and relative insulin deficiency (3)(4)(5)(6).…”

mentioning

confidence: 99%

Phenotypic Type 2 Diabetes in Obese Youth

et al. 2009

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OBJECTIVE— Some obese youth with a clinical diagnosis of type 2 diabetes have evidence of islet cell autoimmunity with positive autoantibodies. In this study, we investigated the differences in insulin sensitivity and secretion between autoantibody-negative (Ab − ) and -positive (Ab + ) youth with clinically diagnosed type 2 diabetes in comparison with control subjects. RESEARCH DESIGN AND METHODS— Sixteen Ab − and 26 Ab + clinically diagnosed type 2 diabetic patients and 39 obese control youth underwent evaluation of insulin sensitivity (3-h hyperinsulinemic-euglycemic clamp), substrate oxidation (indirect calorimetry), first- and second-phase insulin secretion (2-h hyperglycemic clamp), body composition and abdominal adiposity (dual energy X-ray absorptiometry and computed tomography scan, respectively), and glucose disposition index (first-phase insulin secretion × insulin sensitivity). RESULTS— Insulin-stimulated total, oxidative, and nonoxidative glucose disposal, and suppression of fat oxidation during hyperinsulinemia were significantly lower in Ab − compared with Ab + clinically diagnosed type 2 diabetic and control subjects with no difference between the latter two. First- and second-phase insulin secretion and C-peptide were lower in Ab + compared with Ab − type 2 diabetes. Glucose disposition index was not different between the Ab − and Ab + clinically diagnosed type 2 diabetic patients, but both were significantly lower than that in control subjects. Systolic blood pressure and alanine aminotransferase were higher in Ab − versus Ab + clinically diagnosed type 2 diabetic patients, whereas the frequency of ketonuria at diagnosis was higher in Ab + versus Ab − patients. CONCLUSIONS— Islet-cell Ab − clinically diagnosed type 2 diabetic youth are characterized by severe insulin resistance and relative insulin deficiency, whereas Ab + youth have severe insulin deficiency and β-cell failure. The former group has additional features of insulin resistance. These important metabolic differences could influence the natural history of hyperglycemia, insulin dependence, and clinical outcomes in these youth.

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“…In a variety of ethnic groups, obesity is associated with evidence of insulin resistance and impaired insulin secretion among children, as in adults (85,86). Central obesity is of particular importance as a determinant of hyperinsulinemia (87).…”

Section: Insulin Resistancementioning

confidence: 99%