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© 2003 by the American Diabetes Association, Inc.
Pathophysiology/Complications |
Contribution of Abnormal Insulin Secretion and Insulin Resistance to the Pathogenesis of Type 2 Diabetes in Myotonic Dystrophy
1 Section of Nutrition/Metabolism, Istituto Scientifico H San Raffaele, Milan, Italy
2 Unit of Clinical Spectroscopy, Istituto Scientifico H San Raffaele, Milan, Italy
3 Laboratory of Separative Techniques, Istituto Scientifico H San Raffaele, Milan, Italy
4 International Center for the Assessment of Nutritional Status, Università degli Studi di Milano
5 Division of Neurology, Istituto Scientifico H San Raffaele-Università Vita e Salute San Raffaele, Milan, Italy
Address correspondence and reprint requests to Gianluca Perseghin, MD, Internal Medicine, Section of Nutrition/Metabolism & Unit of Clinical Spectroscopy, via Olgettina 60, 20132, Milan, Italy. E-mail: perseghin.gianluca{at}hsr.it.
OBJECTIVE—Myotonic dystrophy (MyD), the most common adult form of muscular dystrophy, is often complicated by diabetes. MyD is dominantly inherited and is due to heterozygosity for a trinucleotide repeat expansion mutation in a protein kinase gene able to induce derangement of RNA metabolism responsible of an aberrant insulin receptor expression.
RESEARCH DESIGN AND METHODS—To assess insulin sensitivity and secretion before the onset of diabetes, we studied 10 MyD patients, 10 offspring of type 2 diabetes (OFF), and 10 healthy subjects with no family history of diabetes (control subjects) with dual X-ray energy absorption, euglycemic-hyperinsulinemic clamp (40 mU/[m2 · min]) combined with infusion of [6,6-D2]-glucose and oral glucose tolerance test (OGTT).
RESULTS—MyD had reduced lean body mass, but peripheral insulin sensitivity was not different to that of control subjects in contrast to OFF, which showed insulin resistance. Insulin secretion, obtained by deconvolution of OGTT data, was also shown to be comparable with that of OFF and control subjects (index of ß-cell function = 
; P = 0.91) even if increased parameters of insulin secretion were found during the first 30 min (30; P = 0.05) of the oral glucose challenge. Fasting plasma proinsulin concentrations (P = 0.01) and the ratio to insulin (P = 0.01) were increased in MyD patients. The proinsulin levels also failed to be suppressed during the clamp and showed exaggerated response after the OGTT. Increased proinsulin levels were shown to be peculiar of MyD patients when compared with OFF.
CONCLUSIONS—In nondiabetic, young MyD patients, insulin sensitivity was preserved, and an increased early secretory response to oral glucose was detected. Abnormal plasma proinsulin levels in the fasting state, during the clamp, and during the OGTT were shown to be secretory dysfunctions peculiar of MyD patients and may be more important than insulin resistance in determining the high risk to develop diabetes in these patients.
Abbreviations: AUC, area under the curve • DEXA, dual energy X-ray absorption • LBM, lean body mass • MyD, myotonic dystrophy • OFF, study group of offspring of diabetic parents • OGTT, oral glucose tolerance test • PIM, proinsulin immunoreactivity • QUICKI, quantitative insulin sensitivity check index • SIp(clamp), clamp-derived index of insulin sensitivity
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  G. Perseghin, M. Comola, P. Scifo, S. Benedini, F. De Cobelli, R. Lanzi, F. Costantino, G. Lattuada, A. Battezzati, A. Del Maschio, et al. Postabsorptive and insulin-stimulated energy and protein metabolism in patients with myotonic dystrophy type 1 Am. J. Clinical Nutrition, August 1, 2004; 80(2): 357 - 364. [Abstract] [Full Text] [PDF]
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