Abnormal release of incretins and cortisol after oral glucose in subjects with insulin-resistant myotonic dystrophy

Abstract

Objective: Although the incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), as well as glucagon and cortisol, are known to influence islet function, the role of these hormones in conditions of insulin resistance and development of type 2 diabetes is unknown. An interesting model for the study of hormonal perturbations accompanying marked insulin resistance without concomitant diabetes is myotonic dystrophy (DM1). Design: The work was carried out in an out-patient setting. Methods: An oral glucose tolerance test was performed in 18 males with DM1 and 18 controls to examine the release of incretins and counter-regulatory hormones. Genetic analyses were also performed in patients. Results: We found that the increment in GLP-1 after oral glucose was significantly greater in patients, while there was no significant difference in GIP or glucagon responses between patients and controls, although long CTG repeat expansions were associated with a more pronounced GIP response. Interestingly, the GLP-1 response to oral glucose correlated with the insulin response in patients but not in controls whereas, in controls, the insulin response closely correlated with the GIP response. Furthermore, cortisol and ACTH levels increased paradoxically in patients after glucose; this was more pronounced in patients with long CTG repeat expansions. Conclusions: This study showed that the GLP-1 and ACTH/cortisol responses to oral glucose are abnormal in insulin-resistant DM1 patients and that CTG triplet repeats are linked to GIP release. These abnormalities may contribute both to the severe insulin resistance and hyperinsulinemia in DM1 and to the preservation of adequate islet function, enabling glucose tolerance to be normal in spite of this marked insulin resistance in DM1.

Systematic thyroid screening in myotonic dystrophy: link between thyroid volume and insulin resistance

“…This relationship has been emphasized in the literature, both in obese people [17, 26] and in normal-weight, hyperinsulinemic, lipodystrophic patients [27]. Indeed, half of our DM patients were overweight, 39% were glucose intolerant or diabetic, and 25% were receiving statins; this confirms the frequency of insulin resistance confirmed by higher 120-min OGTT glucose and insulin levels [28]. This high prevalence of metabolic abnormalities has been demonstrated in other DM cohorts [29], with a range between 14.6 and 21.1% in 1856 patients, with no difference between genders.…”

Leptin and the metabolic syndrome in patients with myotonic dystrophy type 1

“…DM1 is characterized by hormonal disturbances including increase in insulin concentration, abnormal release of cortisol after oral glucose intake, increase in TNFR‐II, hypogonadism and lower testosterone levels (5, 18, 20, 21). Some of these hormones are modulators of leptin expression and secretion.…”

A cross-sectional study for glucose intolerance of myotonic dystrophy

“…Abnormal insulin secretion with preserved insulin sensitivity was also reported in young DM1 patients with preserved motor activity [10]. It seems that pathophysiology of glucose intolerance of DM1 may be quite complicated, since various endocrine and cytokine systems are also involved in DM1 [17][18][19][20][21][22]. Muscle wasting and hypoactivity can also aggravate insulin resistance [23][24][25].…”