Published online before print September 29, 2003, doi: 10.1161/01.CIR.0000091339.70120.53
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(Circulation. 2003;108:1822.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Inflammation in the Prediabetic State Is Related to Increased Insulin Resistance Rather Than Decreased Insulin Secretion
From the Department of Medicine (A.F., S.M.H.), Division of Clinical Epidemiology, University of Texas Health Science Center at San Antonio, Tex; Eli Lilly & Company Area Medical Center (A.F.), Vienna, Austria; Department of Medicine (A.J.G.H.), Mount Sinai Hospital, University of Toronto, Ontario, Canada; Laboratory for Clinical Biochemistry Research (R.P.T.), Department of Pathology, University of Vermont College of Medicine, Burlington, Vt; and Department of Public Health Sciences (R.D.A.), Wake Forest University School of Medicine, Winston Salem, NC.
Correspondence to Steven M. Haffner, MD, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, MC 7873, San Antonio, TX 78229-3900. E-mail haffner{at}uthscsa.edu
Received February 12, 2003; de novo received June 3, 2003; revision received July 23, 2003; accepted July 23, 2003.
Background— Elevated levels of proinflammatory proteins are predictive of both cardiovascular (CV) disease and type 2 diabetes. Previously, atherogenic changes in traditional CV risk factors in the prediabetic state were mainly seen in insulin-resistant subjects rather than in those with a predominant defect in insulin secretion.
Methods and Results— We studied in prediabetic individuals from the Insulin Resistance Atherosclerosis Study (IRAS) the relation of C-reactive protein (CRP), plasminogen activator inhibitor (PAI)-1, and fibrinogen to defects in insulin sensitivity (SI) and first-phase insulin secretion, respectively, as assessed using a frequently sampled intravenous glucose tolerance test. One hundred forty-eight of 906 (16.3%) nondiabetic individuals developed diabetes after a mean follow-up of 5.2 years. Prediabetic individuals who were insulin resistant had higher levels of PAI-1 (mean [95% CI], 25.83 ng/mL [22.42 to 29.77] versus 16.31 ng/mL [12.56 to 21.18]; P=0.003) and CRP (mean [95% CI], 2.88 mg/L [2.33 to 3.56] versus 1.68 mg/L [1.13 to 2.49]; P=0.018) than insulin-sensitive individuals, but individuals with decreased acute insulin response tended to have lower rather than higher levels of inflammatory proteins compared with those with high insulin secretion. Prediabetic subjects who were predominantly insulin resistant had higher levels of inflammatory proteins compared with both prediabetic subjects with decreased insulin secretion as well as nonconverters. By contrast, prediabetic subjects with a predominant defect in first-phase insulin secretion had levels of inflammatory proteins indistinguishable from those in nonconverters.
Conclusions— We have shown an increased proinflammatory state in prediabetic individuals who are predominantly insulin resistant but not in those with a primary defect in ß-cell function. These results provide additional evidence that prediabetic subjects may be at an increased risk of heart disease, and this risk seems to be restricted to subjects with high insulin resistance.
Key Words: cardiovascular diseases • diabetes mellitus • epidemiology • inflammation
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