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- Title
Insulin resistance is a risk factor for progression to Type 1 diabetes.
- Authors
Fourlanos, S.; Narendran, P.; Byrnes, G. B.; Colman, P. G.; Harrison, L. C.
- Abstract
Aims/hypothesis. Glucose homeostasis is determined by an interplay between insulin secretion and insulin action. In Type 1 diabetes, autoimmune destruction of pancreatic beta cells leads to impaired insulin secretion. However, the contribution of impaired insulin action (insulin resistance) to the development of Type 1 diabetes has received little attention. We investigated whether insulin resistance was a risk factor !br progression to Type 1 diabetes. Methods. Islet-antibody-positive first-degree relatives of Type 1 diabetes probands were followed for 4.0 years (median). Insulin secretion was measured as first-phase insulin response (FPIR) to intravenous glucose. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-R). We compared subjects who progressed (n=43) and subjects who did not progress (n=6 1) to diabetes, including 21 pairs matched !br age, sex, islet antibodies and 1-PIR. Results. Progressors had higher insulin resistance relative to insulin secretion at baseline (median HOMA-R : FPIR 0.033 vs 0.013, p<0.0001). According to Cox proportional hazards analysis, islet antibody number, FPIR, Pasting plasma glucose, Pasting serum insulin, HOMA-R and log(HOMA-R : FPIR) were each predictive of progression to diabetes. However, log(HOMA-R : FPIR) (hazard ratio 2.57 per doubling, p<0.001) was the only metabolic variable independently associated with progression. In the matched comparison, progressors had higher Pasting glucose, Pasting insulin, HOMA-R and HOMA-R : 1-PIR, both at baseline and during the follow-up pre-clinical phase. Conclusions/interpretation. Relatives positive for islet antibodies who progress most rapidly to diabetes have a subtle disturbance of insulin-glucose homeostasis years before the onset of symptoms, distinguished by greater insulin resistance for their level of insulin secretion. Taking steps to reduce this insulin resistance could therefore delay the development of Type 1 diabetes.
- Subjects
INSULIN resistance; DISEASE risk factors; DIABETES; AUTOIMMUNE diseases; PANCREATIC beta cells; GLUCOSE; IMMUNOGLOBULINS
- Publication
Diabetologia, 2004, Vol 47, Issue 10, p1661
- ISSN
0012-186X
- Publication type
Article
- DOI
10.1007/s00125-004-1507-3