MODIFICATION OF POSTPRANDIAL HYPERGLYCEMIA WITH INSULIN LISPRO IMPROVES GLUCOSE CONTROL IN PATIENTS WITH TYPE-2 DIABETES

OBJECTIVE - Insulin lispro is a rapid-acting analog of human insulin t hat can be used to target the postprandial rise in plasma glucose. We designed an open-label randomized crossover study of type 2 diabetic p atients with secondary failure of sulfonylurea therapy to determine wh ether improvement of postprandial hyperglycemia would affect total dai ly glucose control. RESEARCH DESIGN AND METHODS - Twenty-five type 2 d iabetic patients who were poorly controlled on a maximum dose of sulfo nylureas were studied in a university hospital clinical research cente r. In one arm of the study, patients continued therapy with maximum-do se sulfonylureas. In the other arm, patients used a combination therap y with insulin lispro before meals and sulfonylureas. After 4 months, patients were crossed over to the opposite arm. Fasting plasma glucose (FPG) and 1- and 2-h postprandial glucose (after a standardized meal) , HbA(1c), total, HDL, and LDL cholesterol, and triglyceride levels we re measured at the end of each arm of the study. RESULTS - Insulin lis pro in combination with sulfonylurea therapy significantly reduced 2-h postprandial glucose concentrations, compared with sulfonylureas alon e, from 18.6 to 14.2 mmol/l (P < 0.0001), and incremental postprandial glucose area from 617.8 to 472.9 mmol . min . l(-1) (P < 0.0007). FPG levels were decreased from 10.9 to 8.5 mmol/l (P < 0.0001), and HbA(1 c) values were reduced from 9.0 to 7.1% (P < 0.0001). Total cholestero l was significantly decreased in the lispro arm from 5.44 to 5.10 mmol /l (P < 0.02). HDL cholesterol concentrations were increased in the li spro arm from 0.88 to 0.96 mmol/l (P < 0.01). The patients weighed sig nificantly more after lispro therapy than after sulfonylureas alone, b ut the difference was small in absolute terms (sulfonylurea therapy al one, 90.6 kg; lispro therapy 93.8 kg; P < 0.0001). Two episodes of hyp oglycemia (glucose concentrations, <2.8 mmol/l) were reported by the p atients while using lispro. CONCLUSIONS - Previously, it has not been possible to address the effect of treatment of postprandial hyperglyce mia specifically. We have now shown that the treatment of postprandial hyperglycemia with insulin lispro markedly improves overall glucose c ontrol and some lipid parameters in patients with type 2 diabetes.