青少年2型糖尿病：胰岛素抵抗、β细胞功能衰竭，还是两者皆有？
Youth type 2 diabetes: insulin resistance, beta-cell failure, or both?
作者信息
Gungor Neslihan, Bacha Fida, Saad Rola, Janosky Janine, Arslanian Silva
机构信息
Division of Pediatric Endocrinology, Children's Hospital of Pittsburgh, 3705 Fifth Ave. at DeSoto St., Pittsburgh, PA 15213, USA.
出版信息
Diabetes Care. 2005 Mar;28(3):638-44. doi: 10.2337/diacare.28.3.638.
OBJECTIVE
This study evaluates insulin sensitivity, pancreatic beta-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 . m(-2) . 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 +/- 1.1 vs. 12.3 +/- 0.5 micromol . kg(-1) . min(-1); P = 0.002). Insulin sensitivity was lower in type 2 diabetic patients than in obese control subjects (1.0 +/- 0.1 vs. 2.0 +/- 0.2 micromol . kg(-1) . min(-1) per pmol/l; P = 0.001). Fasting insulin was higher in type 2 diabetic patients than in obese control subjects (289.8 +/- 24.6 vs. 220.2 +/- 18.0 pmol/l; P = 0.007), and FPIS and SPIS were lower (FPIS: 357.6 +/- 42.0 vs. 1,365.0 +/- 111.0 pmol/l; SPIS: 652.2 +/- 88.8 vs. 1,376.4 +/- 88.8 pmol/l; P < 0.001 for both). The glucose disposition index (GDI = insulin sensitivity x FPIS) was approximately 86% lower in type 2 diabetic patients than in obese control subjects. HbA(1c) correlated with FPIS (r = -0.61, P = 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 beta-cell failure and means of retarding and/or preventing it.
目的
本研究评估2型糖尿病青年患者的胰岛素敏感性、胰岛β细胞功能（BCF）以及二者之间的平衡，并评估糖尿病病程和糖化血红蛋白（HbA1c）与胰岛素敏感性和BCF的关系。
研究设计与方法
研究对象为14例2型糖尿病青少年及20例年龄、BMI、身体成分和青春期情况相近的肥胖对照者。采用3小时高胰岛素血症（80 mU·m⁻²·min⁻¹）正常血糖钳夹技术评估胰岛素敏感性。采用2小时高血糖（12.5 mmol/l）钳夹技术评估第一相胰岛素分泌（FPIS）和第二相胰岛素分泌（SPIS）。使用[6,6-(²)H₂]葡萄糖测定空腹血糖输注速率。
结果
2型糖尿病患者的空腹血糖输注速率高于肥胖对照者（16.5±1.1 vs. 12.3±0.5 μmol·kg⁻¹·min⁻¹；P = 0.002）。2型糖尿病患者的胰岛素敏感性低于肥胖对照者（1.0±0.1 vs. 2.0±0.2 μmol·kg⁻¹·min⁻¹ per pmol/l；P = 0.001）。2型糖尿病患者的空腹胰岛素水平高于肥胖对照者（289.8±24.6 vs. 220.2±18.0 pmol/l；P = 0.007），且FPIS和SPIS较低（FPIS：357.6±42.0 vs. 1365.0±111.0 pmol/l；SPIS：652.2±88.8 vs. 1376.4±88.8 pmol/l；两者P均<0.001）。2型糖尿病患者的葡萄糖处置指数（GDI = 胰岛素敏感性×FPIS）比肥胖对照者低约86%。HbA1c与FPIS相关（r = -0.61，P = 0.025），与胰岛素敏感性无关。
结论
尽管2型糖尿病青年患者的胰岛素敏感性和BCF均受损，但与肥胖对照者相比，BCF的紊乱程度大于胰岛素敏感性。BCF与HbA1c之间的负相关关系可能反映了BCF恶化对血糖控制的影响，或者是BCF上糖毒性现象的一种表现。未来针对2型糖尿病青年患者的研究应针对β细胞功能衰竭的自然病程以及延缓和/或预防其发生的方法。
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