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High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis
Authors:D. A. McClain  D. Abraham  J. Rogers  R. Brady  P. Gault  R. Ajioka  J. P. Kushner
Affiliation:(1) Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA;(2) Salt Lake City Veterans Administration Health Care System, Salt Lake City, UT, USA;(3) Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, 30 N. 2030 East, Salt Lake City, UT 84132, USA
Abstract:Aims/hypothesis The prevalence and mechanisms of diabetes in hereditary haemochromatosis are not known. We therefore measured glucose tolerance, insulin secretory capacity and insulin sensitivity in adults with haemochromatosis.Subjects and methods Subjects recruited from referrals to a haemochromatosis clinic underwent OGTT and frequently sampled IVGTT. A chart review of former clinic patients was also performed.Results The prevalence of diabetes (23%) and IGT (30%) was increased in haemochromatosis compared with matched control subjects (0% diabetes and 14% IGT). Subjects with haemochromatosis and diabetes were overweight (14%) or obese (86%). The prevalence of diabetes, as determined by chart review of fasting glucose values, in subjects who had haemochromatosis and were in the 40–79 years age range was 26%. Overall, patients with haemochromatosis and control subjects had similar values for acute insulin response to glucose and insulin sensitivity. However, patients with haemochromatosis and IGT had a 68% decrease in acute insulin response to glucose (p<0.02) compared with those with NGT. They were not insulin-resistant, exhibiting instead a 62% increase in insulin sensitivity (NS). Haemochromatosis subjects with diabetes exhibited further declines in acute insulin response to glucose, insulin resistance, or both.Conclusions/interpretation Diabetes and IGT are common in haemochromatosis, justifying screening for diabetes and therapeutic phlebotomy. The major abnormality associated with IGT is decreased insulin secretory capacity. Diabetes is usually associated with obesity and concomitant insulin resistance.
Keywords:Diabetes  Haemochromatosis  Impaired glucose tolerance  Insulin resistance  Insulin secretion
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