Endocrine Abstracts (2011) 26 P671

Insulin resistance of multiple metabolic pathways in patients with type 1 diabetes on long term continuous s.c. insulin infusion therapy

E Donga1, M van Dijk1, R P L M Hoogma2, E P M Corssmit1 & J A Romijn1,3

1Leiden University Medical Center, Leiden, The Netherlands; 2Groene Hart Hospital, Gouda, The Netherlands; 3Amsterdam Medical Center, Amsterdam, The Netherlands.

Objective: The aim of the present study was to determine whether insulin resistance is important in well controlled, uncomplicated patients with type 1 diabetes on long term CSII, compared to matched healthy controls.

Research design and methods: We studied 8 patients (4 men and 4 women) with type 1 diabetes on stable continuous subcutaneous insulin pump therapy and 8 healthy controls, matched for age, gender and BMI. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies with infusion of [6,6-2H2] glucose.

Results: Endogenous glucose production (EGP) did not differ in the basal state between patients and controls. However, EGP was less suppressed during clamp conditions in patients compared to controls (64 vs 79%, P=0.01), indicating decreased hepatic insulin sensitivity. During the clamp, glucose disposal rate was ~38% lower in patients compared to controls (24.4±2.5 vs 39.7±5.6 μmol.kgLBM−1.min−1, P=0.04). Accordingly, the rate of infusion of glucose was ~51% lower in patients (17.7±2.8 vs 39.7±5.7 μmol.kgLBM−1.min−1, P=0.02). Finally, NEFA levels were ~2.5 times higher in patients during steady state clamp conditions (150±26 vs 58±4 pmol/l, P=0.01), reflecting decreased insulin sensitivity of lipolysis.

Conclusions: Insulin resistance is a prominent feature of patients with type 1 diabetes on long term and stable treatment with CSII. Insulin resistance involves multiple unrelated metabolic pathways in these patients.

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