Wolffenbuttel B H, Sels J P, Rondas-Colbers G J, Menheere P P
Department of Endocrinology and Metabolism, University Hospital Maastricht, The Netherlands.
Neth J Med. 1999 Feb;54(2):63-9. doi: 10.1016/s0300-2977(98)00145-4.
To assess which factors influence or predict the efficacy of insulin therapy in subjects with type 2 diabetes, who were poorly controlled despite maximal doses of oral glucose lowering agents.
Seventy-five patients with type 2 diabetes participated (mean age (+/- SD), 67 +/- 8 years; body mass index, 25.8 +/- 5.0 kg/m2; median time since diagnosis of diabetes, 8 years (range 1-36); 27 males and 48 females). They were transferred to insulin therapy, in which case either insulin alone, or a combination of insulin and glibenclamide was employed. The importance of baseline parameters (glycaemic control, beta-cell function, measures of insulin resistance) was assessed by comparing good and poor responders (defined as achieved HbA1c < 8.0 or > 9.0%) to insulin therapy, and by multiple logistic regression analysis of these baseline parameters and achieved metabolic control.
During insulin therapy, HbA1c levels decreased from 10.9 +/- 1.3 to 8.2 +/- 1.1% (p < 0.001), and fasting blood glucose levels decreased from 14.0 +/- 2.3 to 8.2 +/- 2.1 mmol/l (p < 0.001). Thirty patients reached HbA1c levels < 8.0%, 21 of them even < 7.5%. The mean increase in body weight was 4.5 kg. HbA1c after 6 months was 7.0 +/- 0.6% in the good responders, and 9.8 +/- 0.6% in the poor responders (p < 0.001), despite a comparable insulin dose. Baseline metabolic control was similar in both groups. Also, glucagon-stimulated and calculated insulin secretion, as well as parameters of insulin resistance, such as fasting serum insulin levels, free fatty acids, and serum triglycerides, were not different between both groups, and certainly not higher in the poor responders. Also previous metformin use was not different. However, poor responders were more obese than good responders, and had significantly longer known duration of diabetes. Multiple logistic regression confirmed that only duration of diabetes and body mass index were independent predictors of response to insulin therapy.
We conclude that in elderly patients with type 2 diabetes improvement of glycaemic control can be achieved at the expense of some weight gain. Measurement of residual insulin secretion prior to institution of insulin treatment does not discriminate between good and poor responders to this model of therapy. Especially in obese patients with longer duration of diabetes more attention is needed in order to achieve optimal glycaemic control. Combination of insulin with newer drugs, like thiazolidinediones, may perhaps achieve this.
评估在尽管使用了最大剂量口服降糖药但血糖控制仍不佳的2型糖尿病患者中,哪些因素会影响或预测胰岛素治疗的疗效。
75例2型糖尿病患者参与研究(平均年龄(±标准差),67±8岁;体重指数,25.8±5.0kg/m²;糖尿病诊断后的中位时间,8年(范围1 - 36年);男性27例,女性48例)。他们转而接受胰岛素治疗,治疗方式为单独使用胰岛素或胰岛素与格列本脲联合使用。通过比较胰岛素治疗的良好应答者和不良应答者(定义为糖化血红蛋白(HbA1c)达到<8.0%或>9.0%),以及对这些基线参数和实现的代谢控制进行多因素逻辑回归分析,评估基线参数(血糖控制、β细胞功能、胰岛素抵抗指标)的重要性。
胰岛素治疗期间,HbA1c水平从10.9±1.3%降至8.2±1.1%(p<0.001),空腹血糖水平从14.0±2.3mmol/L降至8.2±2.1mmol/L(p<0.001)。30例患者的HbA1c水平<8.0%,其中21例甚至<7.5%。体重平均增加4.5kg。尽管胰岛素剂量相当,但良好应答者6个月后的HbA1c为7.0±0.6%,不良应答者为9.8±0.6%(p<0.001)。两组的基线代谢控制相似。此外,胰高血糖素刺激及计算得出的胰岛素分泌,以及胰岛素抵抗参数,如空腹血清胰岛素水平、游离脂肪酸和血清甘油三酯,两组之间并无差异,不良应答者也肯定不更高。既往使用二甲双胍的情况也无差异。然而,不良应答者比良好应答者更肥胖,且糖尿病病程明显更长。多因素逻辑回归证实,只有糖尿病病程和体重指数是胰岛素治疗反应的独立预测因素。
我们得出结论,在老年2型糖尿病患者中,可以通过增加一定体重来实现血糖控制的改善。在开始胰岛素治疗前测量残余胰岛素分泌并不能区分对这种治疗模式的良好应答者和不良应答者。尤其是在糖尿病病程较长的肥胖患者中,为实现最佳血糖控制需要更多关注。胰岛素与噻唑烷二酮类等新型药物联合使用或许可以实现这一点。