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)