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Continuous Subcutaneous Insulin Infusion Therapy Decreases Insulin Resistance in Type 1 Diabetes^*

HANNELE YKI-JÄRVINEN and VEIKKO A. KOIVISTO

Third Department of Medicine, University of Helsinki Haartmaninkatu 4, SF-00290 Helsinki 29, Finland

The influence of continuous sc insulin infusion therapy for 6 weeks on sensitivity to insulin (euglycemic clamp technique) and hepatic glucose production (3-[³H]glucose technique) was measured in 10 type 1 diabetic patients whose mean duration of diabetes was 8 yr. Mean diurnal blood glucose fell from 8.5 ± 0.8 (SEM) mmol/liter to 6.0 ± 0.6 mmol/liter (P < 0.05) and glycosylated hemoglobin from 10.5 ± 0.4% to 8.7 ± 0.3%. Insulin requirements declined by 23% from 47 ± 4 U/day prepump to 36 ± 2 U/day after 6 weeks of pump therapy (P < 0.01). During the insulin clamp, plasma insulin was maintained at approximately 90 mU/liter and plasma glucose at approximately 5.0 mmol/liter in all studies. The rate of glucose metabolism in diabetic patients during conventional therapy (4.65 ± 0.41 mg/kg.min) was 35% lower than in normal subjects (7.20 ± 0.42 mg/kg.min, n = 14, P < 0.001). After 6 weeks of pump therapy, total glucose uptake increased by 27% to 5.90 ± 0.60 mg/kg.min, P < 0.05 us. prepump). This was still 18% lower than in the normal subjects (P < 0.05).

Basal hepatic glucose production in the diabetic patients during conventional therapy (3.07 ± 0.14 mg/kg.min) was 70% higher than in the normal subjects (1.79 ± 0.07mg/kg.min, n = 7, P < 0.001). After 6 weeks of pump therapy, hepatic glucose production fell to 2.48 ± 0.19 mg/kg.min (P < 0.05), which was still 40% higher than in the normal subjects (P < 0.01). Basal hepatic glucose production was directly related to the fasting plasma glucose level (r = 0.67, P < 0.001) and inverselyproportional to fasting insulin concentration (r = –0.48, P < 0.05) in the diabetic patients. Specific tracer insulin binding to erythrocytes in the diabetic patients (19.4 ± 1.5%) was comparable to that in the normal subjects (19.6 ± 1.2%) and remained unchanged during pump therapy. Thus the improved metabolic control resulting from pump therapy is associated with enhancement in sensitivity to insulin, and reduction in basal hepatic glucose production.

^* This study was supported by grants from the Finnish CultureFoundation, the Finnish State Medical Research Council (Academy of Finland), the Foundation for Diabetes Research of the Finnish Diabetes Association, and Nordisk Insulinfond (Gentofte, Denmark).

To whom requests for reprints should be addressed.

Received July 22, 1983.

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