Reduced plasma levels of glucagon-like peptide-1 in elderly men are associated with impaired glucose tolerance but not with coronary heart disease.
OBJECTIVE
Besides the insulinotropic effects of glucagon-like peptide-1 (GLP-1) mimetics, their effects on endothelial dysfunction and myocardial ischaemia are of interest. No previous study has investigated associations between plasma levels of GLP-1 and CHD.


METHODS
We investigated longitudinal relationships of fasting GLP-1 with the dynamic GLP-1 response after OGTT (difference between 60 min OGTT-stimulated and fasting GLP-1 levels [DeltaGLP-1]) and CHD in a population-based cohort of 71-year-old men. In the same cohort, we also cross-sectionally investigated the association between stimulated GLP-1 levels and: (1) cardiovascular risk factors (blood pressure, lipids, urinary albumin, waist circumference and insulin sensitivity index [M/I] assessed by euglycaemic-hyperinsulinaemic clamp); and (2) impaired glucose tolerance (IGT) and type 2 diabetes mellitus.


RESULTS
During the follow-up period (maximum 13.8 years), of 294 participants with normal glucose tolerance (NGT), 69 experienced a CHD event (13.8 years), as did 42 of 141 with IGT and 32 of 74 with type 2 diabetes mellitus. DeltaGLP-1 did not predict CHD (HR 1.0, 95% CI 0.52-2.28). The prevalence of IGT was associated with DeltaGLP-1, lowest vs highest quartile (OR 0.3, 95% CI 0.12-0.58), with no such association for type 2 diabetes mellitus (OR 1.0, 95% CI 0.38-2.86). M/I was significantly associated with DeltaGLP-1 in the type 2 diabetes mellitus group (r = 0.38, p < 0.01), but not in the IGT (r = 0.11, p = 0.28) or NGT (r = 0.10, p = 0.16) groups.


CONCLUSIONS
Impaired GLP-1 secretion is associated with IGT, but not with type 2 diabetes mellitus. This finding in the latter group might be confounded by oral glucose-lowering treatment. GLP-1 does not predict CHD. Although DeltaGLP-1 was associated with insulin sensitivity in the type 2 diabetes mellitus group, GLP-1 does not seem to be a predictor of CHD in insulin-resistant patients.
Nathanson
D
D
Department of Internal Medicine, Karolinska Institutet, Södersjukhuset AB, SE-118 83 Stockholm, Sweden. david.nathanson@sodersjukhuset.se
Zethelius
B
B
Berne
C
C
Holst
J J
JJ
Sjöholm
A
A
Nyström
T
T
D000368:Aged; D000419:Albuminuria; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology; D005215:Fasting; D005500:Follow-Up Studies; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000097:blood / Q000453:epidemiology*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D016019:Survival Analysis; D055105:Waist Circumference
D007328:Insulin; D052216:Glucagon-Like Peptide 1; D002784:Cholesterol