This page will try and summarize information on myotonic dystrophy and diabetes.

Study:

Pathogenesis of Diabetics in Myotonic Dystrophy.

Myotonic dystrophy (MD) is the most common adult form of muscular dystrophy with an estimated prevalence of 1 in 8000 and is often complicated by diabetes. MD is dominantly inherited and is due to heterozygosity for a tri-nucleotide repeat expansion mutation in a protein kinase gene and it was suggested that this induces derangement of RNA metabolism also able to reduce insulin receptor expression. To test whether the abnormal RNA metabolism or a specific malfunction of protein kinase gene may induce insulin resistance prior to the onset of diabetes, we studied 5 glucose-tolerant MD patients (3F/2M, 41 [+ or -] 8yrs, 59 [+ or -] 7 kg, BMI21 [+ or -] 2 kg/[m.sup.2]) and 5 matched healthy subjects, by means of a) dual x-ray energy absorption b) euglycemic-hyperinsulinemic clamp (1 mU/kg/min) c) primed-continuous infusion of 6,6-[d.sup.2]-glucose and I-[sup.13]C-leucine d) indirect calorimetry. Fasting plasma insulin were similar, but proinsulin concentrations were increased in M!

D patients (p=0.01) and the ratio intact proinsulin/insulin (20 [+ or -] 4% vs 5 [+ or -] 1%; p=0.01) was 4-fold higher in MD. MD showed increased body fat mass (35 [+ or -] 5 vs 26 [+ or -] 2%; p=0.05) but lipid oxidation and FFA concentration in the post absorptive and clamp conditions were comparable between the two groups. Glucose metabolism (oxidative and non-oxidative) during insulin stimulation was comparable to normals (6.9 [+ or -] 1.4 vs 8.2 [+ or -] 1.1 mg/]kg FFM.min]; p=0.49). Leucine flux in the post absorptive condition was slightly increased and its sensitivity to insulin was impaired in MD (suppression =8[+ or -]2 vs 19 [+ or -] 2%; p=0.05); also suppression of plasma glutamine (8 [+ or -] 5%) and phenylalanine (8 [+ or -] 2%) concentrations during the clamp were similar than in normals (33 [+ or -] 7 and 15 [+ or] 3% respectively; p=0.05). In summary, MD showed alterations of protein metabolism in both post absorptive and insulin stimulated conditions resulti!

ng in increased proteolysis and muscle wasting. Insulin dependent glucose metabolism is preserved; therefore insulin resistance for glucose is not a major factor in the pathogenesis of diabetes in MD. On the contrary, abnormal insulin cleavage leading to increased proinsulin levels, probably related to specific protein kinase gene malfunction, represents a marker of secretory dysfunction capable to induce diabetes mellitus.

GIANLUCA PERSEGHIN, MAURO COMOLA, CINZIA ARCELLONI, EMANUELA PAGLIATO, ROBERTO LANZI, ALBERTO BATTEZZATI(*), LIVIO LUZI(*), Milan, Italy

(*) ADA Professional Section Member. See Duality of Interest Information.