Assessment of factors associated with pre-diabetes in HCV infection including direct and dynamic measurements of insulin action

N A Mukhtar, C Ayala, J J Maher, M Khalili, N A Mukhtar, C Ayala, J J Maher, M Khalili

Abstract

Although hepatitis C (HCV) is associated with diabetes, few studies have examined pre-diabetes in this population. We aimed to evaluate factors associated with pre-diabetes in HCV-infected patients, including direct measurement of insulin action. Ninety-seven non-cirrhotic, non-diabetic and HCV-infected patients underwent clinical evaluation and oral glucose tolerance testing (OGTT). Insulin sensitivity was measured directly by steady-state plasma glucose (SSPG) concentration during insulin suppression test. Early phase and total insulin secretion were determined using OGTT. Rates of pre-diabetes were as follows: 21% impaired fasting glucose (IFG), 7% impaired glucose tolerance (IGT) and 9% combined IFG/IGT. Twelve percent of Caucasians, 50% of African Americans and 70% of Latinos had pre-diabetes (P = 0.002). Patient characteristics among the glucose metabolism categories were similar except those with combined IFG/IGT had a higher body mass index (BMI) vs normal glucose tolerance (NGT) (30 vs 26 kg/m(2), P = 0.007) and lower LDL vs NGT and IGT (74, 104 and 112 mg/dL, respectively, P ≤ 0.01). On multivariable analysis, non-Caucasian race (OR 23.1, P = 0.003), BMI (OR 3.4, P = 0.02) and greater liver inflammation (OR 7.9, P = 0.03) predicted IFG, whereas non-Caucasian race (OR 14.8, P = 0.01) and SSPG (OR 1.1 per 10 units, P = 0.01) predicted IGT. Early and total insulin secretion adjusted for the degree of insulin resistance was decreased in pre-diabetes compared with NGT (P = 0.01 and P = 0.02, respectively). Pre-diabetes is highly prevalent among HCV-infected patients, and in some instances, coincides with host responses to the virus. In most cases, however, factors that are associated with pre-diabetes in HCV-infected patients are similar to those observed in the non-HCV population.

Conflict of interest statement

Conflict of Interest: No conflicts of interest exist.

© 2011 Blackwell Publishing Ltd.

Figures

Figure 1
Figure 1
A. Plasma glucose responses to oral glucose during OGTT in subjects with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT. Values represent mean plasma glucose concentrations (± SE) measured during OGTT for N=97 patients. B. Plasma insulin responses to oral glucose during OGTT in subjects with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT. Values represent mean plasma insulin concentrations (± SE) measured during OGTT for N=97 patients.
Figure 1
Figure 1
A. Plasma glucose responses to oral glucose during OGTT in subjects with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT. Values represent mean plasma glucose concentrations (± SE) measured during OGTT for N=97 patients. B. Plasma insulin responses to oral glucose during OGTT in subjects with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT. Values represent mean plasma insulin concentrations (± SE) measured during OGTT for N=97 patients.
Figure 2. Insulin resistance (SSPG) by glucose…
Figure 2. Insulin resistance (SSPG) by glucose metabolism categories
Box plots illustrate median and range of SSPG concentrations for all four groups of subjects, with boundaries of the box representing upper and lower quartiles. • Outliers with values between 1.5 and 3 box lengths from the boundaries of the box.

References

    1. NIH Consensus Statement on Management of Hepatitis C: 2002. NIH Consens State Sci Statements. 2002 Jun 10–12;19(3):1–46.
    1. Mehta SH, Brancati FL, Sulkowski MS, Strathdee SA, Szklo M, Thomas DL. Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med. 2000 Oct 17;133(8):592–599.
    1. Karve A, Hayward RA. Prevalence, diagnosis, and treatment of impaired fasting glucose and impaired glucose tolerance in nondiabetic U.S. adults. Diabetes Care. 2010 Nov;33(11):2355–2359.
    1. Levitan EB, Song Y, Ford ES, Liu S. Is nondiabetic hyperglycemia a risk factor for cardiovascular disease? A meta-analysis of prospective studies. Arch Intern Med. 2004 Oct 25;164(19):2147–2155.
    1. Hui JM, Sud A, Farrell GC, Bandara P, Byth K, Kench JG, et al. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected] Gastroenterology. 2003 Dec;125(6):1695–1704.
    1. Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005 Mar;128(3):636–641.
    1. Khalili M, Lim JW, Bass N, Ascher NL, Roberts JP, Terrault NA. New onset diabetes mellitus after liver transplantation: the critical role of hepatitis C infection. Liver Transpl. 2004 Mar;10(3):349–355.
    1. Nathan DM, Davidson MB, DeFronzo RA, Heine RJ, Henry RR, Pratley R, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care. 2007 Mar;30(3):753–759.
    1. Abdul-Ghani MA, DeFronzo RA. Plasma glucose concentration and prediction of future risk of type 2 diabetes. Diabetes Care. 2009 Nov;32(Suppl 2):S194–S198.
    1. Grasso A, Malfatti F, De Leo P, Martines H, Fabris P, Toscanini F, et al. Insulin resistance predicts rapid virological response in non-diabetic, non-cirrhotic genotype 1 HCV patients treated with peginterferon alpha 2b plus ribavirin. J Hepatol. 2009 Dec;51(6):984–990.
    1. Lam KD, Bacchetti P, Abbasi F, Ayala CE, Loeb SM, Shah V, et al. Comparison of surrogate and direct measurement of insulin resistance in chronic hepatitis C virus infection: impact of obesity and ethnicity. Hepatology. 2010 Jul;52(1):38–46.
    1. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003 Jan;26(Suppl 1):S5–S20.
    1. Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995 Dec;19(12):1409–1417.
    1. McLaughlin T, Deng A, Gonzales O, Aillaud M, Yee G, Lamendola C, et al. Insulin resistance is associated with a modest increase in inflammation in subcutaneous adipose tissue of moderately obese women. Diabetologia. [Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural] 2008 Dec;51(12):2303–2308.
    1. Phillips DI, Clark PM, Hales CN, Osmond C. Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabet Med. 1994 Apr;11(3):286–292.
    1. Abdul-Ghani MA, Tripathy D, DeFronzo RA. Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care. 2006 May;29(5):1130–1139.
    1. Abdul-Ghani MA, Williams K, DeFronzo RA, Stern M. What is the best predictor of future type 2 diabetes? Diabetes Care. 2007 Jun;30(6):1544–1548.
    1. Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldstein DE, Little RR, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988–1994. Diabetes Care. 1998 Apr;21(4):518–524.
    1. Festa A, D'Agostino R, Jr, Hanley AJ, Karter AJ, Saad MF, Haffner SM. Differences in insulin resistance in nondiabetic subjects with isolated impaired glucose tolerance or isolated impaired fasting glucose. Diabetes. 2004 Jun;53(6):1549–1555.
    1. Hsu CS, Liu CJ, Liu CH, Wang CC, Chen CL, Lai MY, et al. High hepatitis C viral load is associated with insulin resistance in patients with chronic hepatitis C. Liver Int. 2008 Feb;28(2):271–277.
    1. Fartoux L, Poujol-Robert A, Guechot J, Wendum D, Poupon R, Serfaty L. Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C. Gut. 2005 Jul;54(7):1003–1008.
    1. Kawaguchi T, Yoshida T, Harada M, Hisamoto T, Nagao Y, Ide T, et al. Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3. Am J Pathol. 2004 Nov;165(5):1499–1508.
    1. Aytug S, Reich D, Sapiro LE, Bernstein D, Begum N. Impaired IRS-1/PI3-kinase signaling in patients with HCV: a mechanism for increased prevalence of type 2 diabetes. Hepatology. 2003 Dec;38(6):1384–1392.
    1. Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, et al. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology. 2004 Mar;126(3):840–848.
    1. Abdul-Ghani MA, Jenkinson CP, Richardson DK, Tripathy D, DeFronzo RA. Insulin secretion and action in subjects with impaired fasting glucose and impaired glucose tolerance: results from the Veterans Administration Genetic Epidemiology Study. Diabetes. 2006 May;55(5):1430–1435.
    1. Hanefeld M, Koehler C, Fuecker K, Henkel E, Schaper F, Temelkova-Kurktschiev T. Insulin secretion and insulin sensitivity pattern is different in isolated impaired glucose tolerance and impaired fasting glucose: the risk factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes study. Diabetes Care. 2003 Mar;26(3):868–874.
    1. Weyer C, Bogardus C, Pratley RE. Metabolic characteristics of individuals with impaired fasting glucose and/or impaired glucose tolerance. Diabetes. 1999 Nov;48(11):2197–2203.

Source: PubMed

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