The Use of Continuous Insulin Delivery Systems in Severely Insulin- Resistant Patients

Obese type 2 diabetic patients with severe insulin resistance tend to develop chronic hyperglycemia, despite maximal treatment with diet, physical exercise, and oral hypoglycemic agents. Insulin therapy in these patients usually does not lead to satisfactory glucose control, even when the insulin dosage is very high. High doses of insulin also cause weight to increase, which aggravates insulin resistance and exacerbates other cardiovascular risk factors.

Continuous subcutaneous insulin infusion (CSII) provided by an insulin pump reduces the incidence of both postprandial hyperglycemia and severe hypoglycemia. To determine whether CSII has a beneficial effect on insulin resistance in obese type 2 diabetic patients with severe insulin resistance, a trial of CSII was initiated in this group.

A total of 10 severely obese (BMI > 30 kg/m²) type 2 diabetic patients with severe insulin resistance (insulin dose of > 1 U · kg⁻¹ · day⁻¹) were recruited from a hospital-based practice. Subjects who qualified for the study had an HbA_1c > 8.5%, despite strict diet and compliance with the insulin regimen. After receiving training, patients were started on an insulin pump (Minimed 507) . Blood glucose levels were monitored with a glucometer and patients were instructed to measure their blood glucose at least four times a day. Insulin dosage was optimalized by the study physician. Weight, insulin dose, and HbA_1c levels were measured at baseline and throughout the study.

The patients’ age (mean ± SD) was 59 ± 10 years. The duration of the study was 40 weeks. All subjects in the study had a reduction in insulin requirements (in units per kilogram per day) from 1.46 ± 0.43 (mean ± SD) at week 0 to 1.19 ± 0.42 at week 40. Concomitantly, there was a slight decrease in weight (in kilograms), from 95.9 ± 13.2 at week 0 to 93.4 ± 12.7 at week 40. Most significantly, glycemic control improved, with a decrease in the percentage of HbA_1c levels from 12.34 ± 1.74 at week 0 to 9.56 ± 0.76 at week 40.

These findings suggest that CSII may be an effective therapy to reduce insulin resistance in obese type 2 diabetic patients without the deleterious side-effects associated with increasing insulin dosage. To further determine the effectiveness of CSII, the Israeli Diabetes Research Group is now conducting a randomized clinical trial with a cross-over design comparing CSII with intensive multiple-injection insulin treatment in this population.