磺脲类药物撤药对非胰岛素依赖型糖尿病患者胰岛素原水平、B细胞功能及葡萄糖处置的影响。

Effect of sulfonylurea withdrawal on proinsulin levels, B cell function, and glucose disposal in subjects with noninsulin-dependent diabetes mellitus.

作者信息

Prigeon R L, Jacobson R K, Porte D, Kahn S E

机构信息

Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, USA.

出版信息

J Clin Endocrinol Metab. 1996 Sep;81(9):3295-8. doi: 10.1210/jcem.81.9.8784086.

DOI:10.1210/jcem.81.9.8784086

PMID:8784086

Abstract

To examine the effect of sulfonylurea withdrawal on the proinsulin (PI) to immunoreactive insulin (IRI) ratio in subjects with noninsulin dependent diabetes mellitus (NIDDM), we measured fasting and arginine-stimulated PI and IRI levels in 15 subjects with NIDDM (mean age, 64.4 yr; body mass index, 27.3 kg/m2) during chronic treatment with glyburide (n = 12) or other sulfonylureas (n = 3) and after withdrawal from the medication for 2-4 weeks. Additionally, we performed iv glucose tolerance tests to measure the insulin sensitivity index, glucose effectiveness at zero insulin, iv glucose tolerance, and the acute insulin response to glucose. Discontinuation of sulfonylurea therapy resulted in an increase in fasting plasma glucose from 10.5 +/- 0.8 to 13.1 +/- 0.9 mmol/L (P < 0.001). This was associated with a decrease in the fasting IRI concentration (120 +/- 21 to 92 +/- 21 pmol/L; P < 0.005) and the fasting PI concentration (58 +/- 10 to 41 +/- 7 pmol/L; P < 0.01); however, the PI/IRI ratio did not differ (50 +/- 6% during medication and 48 +/- 5% after withdrawal; P = 0.43). Similarly, the acute PI/IRI ratio did not change (8.6 +/- 2.4% on therapy; 8.4 +/- 1.2% off therapy; P = 0.91). No change was observed in other metabolic parameters, including insulin sensitivity index (0.76 +/- 0.21 x 10(-5) min-1/pM on therapy; 0.76 +/- 0.19 x 10(-5) min-1/pM off therapy), acute insulin response to arginine (225 +/- 37 pmol/L on therapy; 225 +/- 40 pmol/L off therapy), acute insulin response to glucose (10 +/- 6 pmol/L on therapy; 5 +/- 4 pmol/L off therapy), glucose effectiveness at zero insulin (0.0127 +/- 0.0007 min-1 on therapy; 0.0119 +/- 0.0009 min-1 off therapy), and iv glucose tolerance (0.85 +/- 0.05%/min on therapy; 0.71 +/- 0.07%/min off therapy). We conclude that sulfonylurea therapy does not correct the elevated PI/IRI ratio or absent first phase insulin response of NIDDM and does not have an effect on parameters of peripheral tissue glucose uptake.

摘要

为研究停用磺脲类药物对非胰岛素依赖型糖尿病（NIDDM）患者胰岛素原（PI）与免疫反应性胰岛素（IRI）比值的影响，我们测定了15例NIDDM患者（平均年龄64.4岁；体重指数27.3kg/m²）在使用格列本脲（n = 12）或其他磺脲类药物（n = 3）进行长期治疗期间以及停药2 - 4周后的空腹及精氨酸刺激后的PI和IRI水平。此外，我们进行了静脉葡萄糖耐量试验，以测量胰岛素敏感性指数、零胰岛素状态下的葡萄糖效能、静脉葡萄糖耐量以及对葡萄糖的急性胰岛素反应。停用磺脲类药物治疗导致空腹血糖从10.5±0.8mmol/L升高至13.1±0.9mmol/L（P < 0.001）。这与空腹IRI浓度降低（从120±21pmol/L降至92±21pmol/L；P < 0.005）和空腹PI浓度降低（从58±10pmol/L降至41±7pmol/L；P < 0.01）相关；然而，PI/IRI比值并无差异（用药期间为50±6%，停药后为48±5%；P = 0.43）。同样，急性PI/IRI比值也未改变（治疗时为8.6±2.4%；停药后为8.4±1.2%；P = 0.91）。其他代谢参数未见变化，包括胰岛素敏感性指数（治疗时为0.76±0.21×10⁻⁵min⁻¹/pM；停药后为0.76±0.19×10⁻⁵min⁻¹/pM）、对精氨酸的急性胰岛素反应（治疗时为225±37pmol/L；停药后为225±40pmol/L）、对葡萄糖的急性胰岛素反应（治疗时为10±6pmol/L；停药后为5±4pmol/L）、零胰岛素状态下的葡萄糖效能（治疗时为0.0127±0.0007min⁻¹；停药后为0.0119±0.0009min⁻¹）以及静脉葡萄糖耐量（治疗时为0.85±0.05%/min；停药后为0.71±0.07%/min）。我们得出结论，磺脲类药物治疗不能纠正NIDDM患者升高的PI/IRI比值或缺失的第一相胰岛素反应，且对周围组织葡萄糖摄取参数无影响。