Insulin, Glucagon and Growth Hormone and CIMT in Glucose Intolerance
AbstractObjective: There is an increasing evidence that glucagon and growth hormone (GH)-insulin-like growth factor (IGF) axis may play an important role in glucose metabolism since early stages of glucose intolerance. Carotid intima media thickness is a marker for subclinical atherosclerosis. We aimed to evaluate glucagon, GH and IGF-1 in prediabetic states and their relationship with carotid intima media thickness.Methods: One hundred subjects underwent a 75 gr oral glucose tolerance test and were divided into 4 groups according to their state of glucose tolerance: (i) normal glucose tolerance (NGT)/Controls (n=21), (ii) impaired glucose tolerance (IGT) (n=35), (iii) impaired fasting glucose (IFG) (n=22), (iv) type 2 diabetes mellitus (n=22). Insulin, glucagon and GH were measured at 0, 60 and 120. minutes of OGTT and their area under the curve (AUC) were calculated. Fasting IGF-1 levels and carotid intima media thickness were determined in all participants. Results: AUC for Glucagon was significantly higher in subjects with IGT, IFG and type 2 diabetes mellitus compared to NGT subjects. AUC for GH was significantly higher in subjects with IFG compared to subjects with IGT, type 2 diabetes mellitus and NGT. Plasma IGF-1 levels were significantly lower in subjects with abnormal glucose tolerance. CIMT was significantly higher in IFG group and CIMT was found to be negatively correlated with IGF-1 levels in subjects with IFG. Conclusion: There are pathological alterations of glucagon, GH-IGF-1 and insulin in prediabetic stages. Among these alterations insulin resistance and IGF-1 are associated with CIMT. Further studies needed to investigate the role of treatments targeting insulin sensitivity will have an impact on the association between insulin and early atherogenesis
Del Prato S, Marchetti P. Beta- and alpha-cell dysfunction in type 2 diabetes. Horm Metab Res 2004;36:775-81.
DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am 2004;88:787-835, ix.
Holt RI, Simpson HL, Sonksen PH. The role of the growth hormone-insulin-like growth factor axis in glucose homeostasis. Diabet Med 2003;20:3-15.
Diabetes mellitus: a major risk factor for cardiovascular disease. A joint editorial statement by the American Diabetes Association; The National Heart, Lung, and Blood Institute; The Juvenile Diabetes Foundation International; The National Institute of Diabetes and Digestive and Kidney Diseases; and The American Heart Association. Circulation 1999;100:1132-3.
Karbek B, Cakal E, Cakir E, et al. Cardiovascular risk factors, carotid artery intima media thickness, and HSCRP levels in patients with impaired glucose metabolism. Minerva Endocrinol 2013;38:297-304.
Shin JY, Lee HR, Lee DC. Increased arterial stiffness in healthy subjects with high-normal glucose levels and in subjects with pre-diabetes. Cardiovasc Diabetol 2011;10:30.
American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes Care 2013;36 Suppl 1:S67-74.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry 1972;18:499-502.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-9.
Spellman CW. Pathophysiology of type 2 diabetes: targeting islet cell dysfunction. J Am Osteopath Assoc 2010;110:S2-7.
Virally M, Blickle JF, Girard J, Halimi S, Simon D, Guillausseau PJ. Type 2 diabetes mellitus: epidemiology, pathophysiology, unmet needs and therapeutical perspectives. Diabetes Metab 2007;33:231-44.
Dunning BE, Gerich JE. The role of alpha-cell dysregulation in fasting and postprandial hyperglycemia in type 2 diabetes and therapeutic implications. Endocr Rev 2007;28:253-83.
Sarraju A, Kim SH, Knowles JW. Cardiometabolic Effects of Glucagon-Like Peptide-1 Agonists. Curr Atheroscler Rep 2016;18:7.
Colao A, Spiezia S, Di Somma C, et al. Circulating insulin-like growth factor-I levels are correlated with the atherosclerotic profile in healthy subjects independently of age. J Endocrinol Invest 2005;28:440-8.
Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D. The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study. The Journal of clinical endocrinology and metabolism 2004;89:114-20.
Denti L, Annoni V, Cattadori E, et al. Insulin-like growth factor 1 as a predictor of ischemic stroke outcome in the elderly. The American journal of medicine 2004;117:312-7.
Spilcke-Liss E, Friedrich N, Dorr M, et al. Serum Insulin-like Growth Factor-I and its Binding Protein 3 in their Relation to Intima Media Thickness: Results of the Study of Health in Pomerania (SHIP). Clinical endocrinology 2011.
Sirbu A, Nicolae H, Martin S, et al. IGF-1 and Insulin Resistance Are Major Determinants of Common Carotid Artery Thickness in Morbidly Obese Young Patients. Angiology 2016;67:259-65.
Martin RM, Gunnell D, Whitley E, et al. Associations of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein (IGFBP)-2 and IGFBP-3 with ultrasound measures of atherosclerosis and plaque stability in an older adult population. The Journal of clinical endocrinology and metabolism 2008;93:1331-8.
Arnqvist HJ, Bornfeldt KE, Chen Y, Lindstrom T. The insulin-like growth factor system in vascular smooth muscle: interaction with insulin and growth factors. Metabolism 1995;44:58-66.
Wang J, Razuvaev A, Folkersen L, et al. The expression of IGFs and IGF binding proteins in human carotid atherosclerosis, and the possible role of IGF binding protein-1 in the regulation of smooth muscle cell proliferation. Atherosclerosis 2012;220:102-9.
Berryman DE, Glad CA, List EO, Johannsson G. The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations. Nat Rev Endocrinol 2013;9:346-56.
Andreozzi F, Gastaldelli A, Mannino GC, et al. Increased carotid intima-media thickness in the physiologic range is associated with impaired postprandial glucose metabolism, insulin resistance and beta cell dysfunction. Atherosclerosis 2013;229:277-81.
Roussel R, Natali A, Balkau B, et al. Beta-cell function is associated with carotid intima-media thickness independently of insulin resistance in healthy individuals. J Hypertens 2016;34:685-91.
Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 2006;113:1888-904.
Sesti G, Sciacqua A, Cardellini M, et al. Plasma concentration of IGF-I is independently associated with insulin sensitivity in subjects with different degrees of glucose tolerance. Diabetes Care 2005;28:120-5.
Rajpathak SN, Gunter MJ, Wylie-Rosett J, et al. The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetes. Diabetes Metab Res Rev 2009;25:3-12.
All opinions and reports within the articles that are published in the Gazi Medical Journal are the personal opinions of author(s). Gazi University, Editors and the publisher do not accept any responsibility for these articles. The journal is printed on acid-free paper.