Insulin Supplement in Type 2 Diabetic Patients with Secondary Failure to Oral Agents Ameliorates Hepatic and Peripheral Insulin Sensitivity but not Insulin Secretion

In order to investigate the mechanism of amelioration of metabolic abnormalities with supplementary doses of insulin, islet B‐cell function and insulin sensitivity were measured in 10 patients with Type 2 diabetes in secondary failure to oral agents. A small dose of ultralente insulin (0.26 ± 0.07 U kg‐ideal‐body‐weight⁻¹) was added in the morning before breakfast. After 3 months insulin therapy and progressive improvement of metabolic control (HbA₁ from 10.5 ± 0.4 to 9.0 ± 0.3 % at the end of insulin treatment, p < 0.001), basal C‐peptide and incremental area during an oral glucose tolerance test were unchanged. In vivo peripheral insulin sensitivity (euglycaemic clamp with insulin infusion of 40, 160, and 600 mU m⁻² min⁻¹, respectively) was significantly improved (glucose requirement: to 4.7 ± 1.0 from 3.0 ± 0.6 mg kg⁻¹ min⁻¹, p< 0.05 at first insulin level; to 10.8 ± 0.5 from 9.3 ± 0.7 mg kg⁻¹ min⁻¹, p<0.01 at second level; to 13.3 ± 0.6 from 11.8 ± 0.8 mg kg⁻¹ min⁻¹, p< 0.025 at third level). Basal hepatic glucose production was also significantly reduced (from 4.3 ± 0.4 to 3.3 ± 0.3 mg kg⁻¹ min⁻¹, p< 0.05), and residual glucose production further suppressed after insulin supplement (from 1.1 ± 0.4 to 0.3 ± 0.2 mg kg⁻¹ min⁻¹ after 120 min at 100 mU I⁻¹ plasma insulin, p< 0.05). Specific insulin binding to mononuclear leucocytes was unchanged (from 3.1 ± 0.3 to 3.5 ± 0.3 %, NS). 1990 Diabetes UK