Prognostic factors for successful insulin therapy in subjects with type 2 diabetes

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.