Reduced plasma levels of glucagon-like peptide-1 in elderly men are associated with impaired glucose tolerance but not with coronary heart disease
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.
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 [ΔGLP-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.
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. ΔGLP-1 did not predict CHD (HR 1.0, 95% CI 0.52–2.28). The prevalence of IGT was associated with ΔGLP-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 ΔGLP-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.
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 ΔGLP-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.
- Nyström, T (2008) The potential beneficial role of glucagon-like peptide-1 in endothelial dysfunction and heart failure associated with insulin resistance. Horm Metab Res 40: pp. 593-606 CrossRef
- Toft-Nielsen, MB, Damholt, MB, Madsbad, S (2001) Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 86: pp. 3717-3723 CrossRef
- Zethelius, B, Byberg, L, Hales, CN, Lithell, H, Berne, C (2002) Proinsulin is an independent predictor of coronary heart disease: report from a 27-year follow-up study. Circulation 105: pp. 2153-2158 CrossRef
- Nyström, T, Gutniak, MK, Zhang, Q (2004) Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol 287: pp. E1209-E1215 CrossRef
- Byberg, L, McKeigue, PM, Zethelius, B, Lithell, HO (2000) Birth weight and the insulin resistance syndrome: association of low birth weight with truncal obesity and raised plasminogen activator inhibitor-1 but not with abdominal obesity or plasma lipid disturbances. Diabetologia 43: pp. 54-60 CrossRef
- Merlo, J, Lindblad, U, Pessah-Rasmussen, H (2000) Comparison of different procedures to identify probable cases of myocardial infarction and stroke in two Swedish prospective cohort studies using local and national routine registers. Eur J Epidemiol 16: pp. 235-243 CrossRef
- DeFronzo, RA, Tobin, JD, Andres, R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237: pp. E214-E223
- Prigeon, RL, Quddusi, S, Paty, B, D'Alessio, DA (2003) Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect. Am J Physiol 285: pp. E701-E707
- Mannucci, E, Ognibene, A, Cremasco, F (2001) Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care 24: pp. 489-494 CrossRef
- Reduced plasma levels of glucagon-like peptide-1 in elderly men are associated with impaired glucose tolerance but not with coronary heart disease
Volume 53, Issue 2 , pp 277-280
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- Coronary heart disease
- Glucagon-like peptide-1
- Impaired glucose tolerance
- Type 2 diabetes
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- Author Affiliations
- 1. Department of Internal Medicine, Karolinska Institutet, Södersjukhuset AB, SE-118 83, Stockholm, Sweden
- 2. Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
- 3. Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden
- 4. Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark