ALTERATIONS IN IMMUNOREACTIVE PROINSULIN AND INSULIN-CLEARANCE INDUCED BY WEIGHT-LOSS IN NIDDM
ALTERATIONS IN IMMUNOREACTIVE PROINSULIN AND INSULIN-CLEARANCE INDUCED BY WEIGHT-LOSS IN NIDDM
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DOI：
10.2337/diabetes.43.7.871
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发表时间：
1994-07-01
期刊：
影响因子：
7.7
通讯作者：
HENRY, RR
中科院分区：
文献类型：
--
作者：
POLONSKY, KS;GUMBINER, B;HENRY, RR
对显性非胰岛素依赖型糖尿病（NIDDM）患者与肥胖非糖尿病对照组和亚临床糖尿病患者进行了比较研究。胰腺胰岛素分泌率测定外周C肽在24小时内，而受试者消耗等热量的混合饮食的去卷积。然后受试者进行至少6周的热量限制，在此期间体重下降至少10%。然后恢复固体混合膳食再喂养至少2周，直到达到等热量摄入，然后重复膳食曲线。减肥前，亚临床糖尿病患者的胰岛素、C肽和胰岛素分泌率显著高于其他两组。两组糖尿病患者的胰岛素原浓度显著高于对照组，但是，当以总胰岛素免疫反应性的百分比表示时，仅在显性糖尿病组中差异显著。由于低热量喂养导致体重减轻，内源性分泌的胰岛素的清除率显着增加，但不影响C肽的清除。在肥胖受试者和亚临床糖尿病患者中，体重减轻与胰岛素分泌率降低相关，可能是胰岛素敏感性改善的结果。在显性糖尿病和高血糖症患者中，体重减轻改善了β细胞对葡萄糖的反应性，并与胰岛素清除率增加和胰岛素原免疫反应性降低相关。由于胰岛素清除率的变化和胰岛素原对总胰岛素免疫反应性的贡献，单独测量总胰岛素样免疫反应性可能会在比较胰岛素抵抗、葡萄糖耐受不良和糖尿病患者体重减轻前后的β细胞功能时提供误导性信息。
Subjects with overt non-insulin-dependent diabetes mellitus (NIDDM) were studied in comparison to obese nondiabetic control subjects and patients with subclinical diabetes. Pancreatic insulin secretion rates were measured by deconvolution of peripheral C-peptide over a 24-h period while subjects consumed an isocaloric mixed diet. Subjects mere then placed on caloric restriction for at least 6 weeks, during which time body weight fell by at least 10%. Refeeding with solid mixed meals was then resumed for at least 2 weeks until isocaloric intake was attained, and then the meal profiles were repeated. Before weight loss, insulin, C-peptide, and insulin secretion rates were significantly higher in subjects with subclinical diabetes than in the other two groups. Proinsulin concentrations were significantly greater in the two diabetic groups than in control subjects, but, when expressed as a percentage of the total insulin immunoreactivity, the differences were significant only in the group with overt diabetes. Weight loss because of hypocaloric feeding resulted in a significant increase in the rate of clearance of endogenously secreted insulin but did not affect the clearance of C-peptide. In obese subjects and those with subclinical diabetes, weight loss was associated with a reduction in insulin secretion rates, presumably as a result of improvements in insulin sensitivity. In patients with overt diabetes and hyperglycemia, weight loss improved beta-cell responsiveness to glucose and was associated with an increase in insulin clearance and a reduction in proinsulin immunoreactivity. As a result of changes in insulin clearance and the contribution of proinsulin to total insulin immunoreactivity, measurement of total insulin-like immunoreactivity alone may provide misleading information in comparing beta-cell function before and after weight loss in patients with insulin resistance, glucose intolerance, and diabetes.