Improved beta-cell function after intensive insulin treatment in severe non-insulin-dependent diabetes

In type II, non-insulin-dependent diabetes, insulin secretion is often reduced to the point where oral hypoglycaemic agents fail to control the plasma glucose level. We studied 12 patients (age 41-66 years; 4 lean, 8 obese) with Type II diabetes mellitus for 1-25 years who were uncontrolled despite maximal dose glibenclamide and metformin. After withdrawal of medication, blood glucose control was determined by measuring glucose before and 2 h after each meal for 48 h, and beta-cell function by insulin or C-peptide response to glucagon and to iv glucose. Following these tests, intensive insulin treatment (CSII) was initiated, and near-euglycaemia (mean of 7 daily glucose determinations < 7.7 mmol/l) was maintained for 16.6 ± 1.5 days, at which time the tests were repeated. Mean daily insulin requirement was 61 ± 9 IU (0.81 ± 0.09 IU/kg). Glucose control was improved after cessation of CSII (mean glucose 12.7 ± 0.6 mmol/l after vs 20 ± 1.5 mmol/l before, P < 0.005). Maximum incremental C-peptide response improved both to glucagon (214 ± 32 after vs 134 ± 48 pmol/l before, P = 0.05) and to glucose iv bolus injection (284 ± 53 vs 113 ± 32 pmol/l, P < 0.05). Peak insulin response, measured after iv glucose infusion, also tended to be higher in the post-CSII test (42 ± 18 vs 22 ± 5.6 mU/l). Basal and stimulated proinsulin concentrations were high relative to C-peptide levels during the pre-treatment period, but returned to normal after CSII. Thus: 1) adequate blood glucose control could be obtained in most of our patients using moderate doses of insulin even in those who were obese; 2) short-term euglycaemia resulted in improved insulin response to both glucagon and glucose, and reduction of the relative proinsulin secretion; 3) although beta-cell function improved in most patients, only 6 could be adequately controlled with oral agents after hospital discharge. In those patients who do not respond well to conventional treatment, CSII is an attractive alternative.