c-peptide and Myotonic-Dystrophy

Growth hormone (GH) levels were measured in 12 patients with myotonic dystrophy (MD; 7 men and 5 women, aged 21-49 years) and 14 volunteers after administration of 100 micrograms GH-releasing hormone (GHRH; 1-29). A 75-g oral glucose tolerance test was carried out to determine glucose, insulin, plasma C-peptide, and urinary C-peptide. The GH level in six MD patients responded normally to GHRH (group I), with a peak of 17.1 +/- 1.46 micrograms/l, compared with controls (27.8 +/- 19.6 micrograms/l, NS), and that in the other six patients responded subnormally, with a peak of 3.15 +/- 1.46 micrograms/l, lower than in controls and in group I patients (P < 0.001). In group I the insulin response to the glucose tolerance test showed hyperinsulinism and was lower than that in group II patients; stimulated C-peptide was also higher in group II than in group I and in controls; urinary C-peptide levels were parallel to those in previous data. In all MD patients there were a negative correlation between absolute values of GH response to GHRH and insulin response to glucose tolerance test (r = -0.79, P < 0.001). Our data suggest that the failure in GH release and peripheral insulin action is due to a generalized defect in cellular membrane function in MD patients.

Topics: Adult; C-Peptide; Evaluation Studies as Topic; Female; Glucose Tolerance Test; Growth Hormone; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Myotonic Dystrophy

One of the clinical features of myotonic dystrophy is insulin resistance with non-obese diabetes mellitus (DM). Recently, the mechanism of insulin resistance in patients with myotonic dystrophy was revealed. The optimal treatment of DM with myotonic dystrophy has not been established. We report the effect of metformin in a patient with myotonic dystrophy without obesity.. A 58-year-old woman (BMI = 22.1 kg/m2) with myotonic dystrophy and DM was followed at our clinic. She had been treated with glimepiride for DM for the last 6 months, without achieving good control (HbA(1c) 9.3%). She was admitted with congestive heart failure and cholecystitis. She was treated with diuretics, antibiotics and insulin. As her blood glucose fell, we discontinued insulin and started glimepiride, but her glycaemic control had worsened. We started metformin instead of glimepiride. After 4 weeks of metformin, HbA(1c) was decreased to 7.4%, while HOMA-IR during glimepiride treatment was 4.9, and 3.7 with metformin. Three months later, HbA(1c) was maintained (7.5%).. It is important to choose the optimal treatment for DM in myotonic dystrophy, because the patients have hyperinsulinemia caused by specific mechanism and could not reduce the insulin resistance. Metformin improved hyperglycemia through increased insulin-independent glucose uptake in peripheral muscle. We believe metformin is the optimal agent for these patients.

Topics: Blood Glucose; C-Peptide; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Metformin; Middle Aged; Myotonic Dystrophy; Sulfonylurea Compounds

Hyperinsulinaemia is a reported feature of the inherited multisystem disorder myotonic dystrophy. This phenomenon has been attributed to a compensatory beta cell response to tissue insulin resistance. In this study, circulating concentrations of insulin, proinsulin, and split proinsulin molecules were determined after an overnight fast in ten patients with myotonic dystrophy using two-site monoclonal antibody-based immunoradiometric assays. Results were compared with ten healthy control subjects matched for age, gender, and body mass index. Oral glucose tolerance (75 g), as defined by World Health Organization criteria, was normal in all subjects. Fasting plasma immunoreactive insulin concentration, as determined using a conventional radioimmunoassay, was almost three times higher (p < 0.005) in the myotonic dystrophy patients than the healthy control subjects. By contrast, fasting concentrations (mean +/- SEM) of C-peptide (0.75 +/- 0.09 vs 0.52 +/- 0.03 nmol/l, p = 0.07) and immunoradiometrically-determined insulin (60 +/- 12 vs 38 +/- 4 pmol/l, p = 0.09) were not significantly different between the groups. Fasting concentrations of proinsulin (10.3 +/- 2.9 vs 1.6 +/- 0.3 pmol/l, p < 0.01), and 32-33 split proinsulin (7.8 +/- 2.5 vs 2.9 +/- 0.4 pmol/l, p < 0.05) were significantly elevated in the patients with myotonic dystrophy. Accordingly, the mean fasting proinsulin:insulin ratio, expressed as a percentage, was significantly increased in the myotonic patients (20 +/- 5 vs 4 +/- 1%, p < 0.01). The overall C-peptide response to the oral glucose challenge was significantly greater in the myotonic patients compared with the healthy control subjects (p < 0.001). These results provide corroborative evidence of increased beta-cell secretion in myotonic dystrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: C-Peptide; Fasting; Glucose Tolerance Test; Humans; Insulin; Myotonic Dystrophy; Proinsulin; Radioimmunoassay; Reference Values