Intensive Conventional Insulin Therapy for Type II Diabetes: Metabolic effects during a 6-mo outpatient trial

Objective— To determine whether tight glycemic control can be obtained using intensive conventional split-dose insulin therapy in the outpatient management of type II diabetes without development of unacceptable side effects. Research Design and Methods— Fourteen type II diabetic subjects were treated with an intensive program of conventional insulin (subcutaneous NPH and regular insulin before breakfast and supper) for 6 mo. Insulin dose adjustments were based on an algorithm built on frequent CPG measurements (4–6 times/day). Patients were monitored biweekly as outpatients and admitted 1 day/mo for metabolic evaluation. Results— Glycemic control was achieved by 1 mo (mean plasma glucose fell from 17.5 ± 0.9 to 7.7 ± 0.7 mM, P < 0.001) and remained in this range thereafter. Hypoglycemic events at 1 mo were infrequent (mean ± SE events per patient per month: 4.1 ± 0.3) and mild in nature, and progressively decreased to 1.3 ± 0.5 events/mo by 6 mo. After treatment, basal HGO fell 44% from 628 ± 44 to 350 ± 17 μmol·m−2·min−1 (P < 0.001), and maximal rates of glucose disposal measured by hyperinsulinemic euglycemic clamp (1800 pmol·m−2·min−1) improved from 1418 ± 156 to 1657 ± 128 μmol·m−2·min−1 (P < 0.05). The total dose of exogenous insulin required was 86 ± 13 U at 1 mo and 100 ± 24 U at 6 mo. During treatment, mean serum insulin levels increased from 308 ± 80 to 510 ± 102 pM (P < 0.05), while body weight increased from 93.5 ± 5.8 to 102.2 ± 6.8 kg (P < 0.001). Both pre- and posttreatment glucose disposal rates correlated with the total exogenous insulin dose required to achieve glycemic control (r = −0.75 and −0.78, both P < 0.005). Weight gain was inversely related to the pretreatment glucose disposal rate (r = −0.53, P < 0.05) and directly correlated with both mean day-long serum insulin level (r = 0.67, P < 0.01) and total exogenous insulin dose (r = 0.62, P < 0.02). Conclusions— Intensive CIT, when combined with CBG measurements, can be used to rapidly improve glycemic control in type II diabetes without development of unacceptable hypoglycemia. This degree of metabolic improvement, however, requires large doses of exogenous insulin to overcome peripheral insulin resistance and results in greater hyperinsulinemia with progressive weight gain.