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

TY - JOUR

T1 - Abnormal release of incretins and cortisol after oral glucose in subjects with insulin-resistant myotonic dystrophy

AU - Johansson, Asa

AU - Olsson, Tommy

AU - Cederquist, Kristina

AU - Forsberg, Hakan

AU - Holst, Jens Juul

AU - Seckl, Jonathan R

AU - Ahren, Bo

PY - 2002/3

Y1 - 2002/3

N2 - 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.

AB - 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.

KW - Adult

KW - Body Composition

KW - DNA

KW - Dose-Response Relationship, Drug

KW - Gastrointestinal Hormones

KW - Glucagon

KW - Glucagon-Like Peptide 1

KW - Glucagon-Like Peptides

KW - Glucose

KW - Humans

KW - Hydrocortisone

KW - Insulin Resistance

KW - Male

KW - Middle Aged

KW - Myotonic Dystrophy

KW - Peptide Fragments

KW - Regression Analysis

KW - Repetitive Sequences, Nucleic Acid

M3 - Journal article

C2 - 11888847

SN - 0804-4635

VL - 146

SP - 397

EP - 405

JO - Acta Endocrinologica, Supplement

JF - Acta Endocrinologica, Supplement

IS - 3

ER -