Insulin Sensitivity and Variability in Hepatitis C Virus Infection Using Direct Measurement
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Background and Aims
Studies investigating insulin resistance (IR) in chronic hepatitis C virus (HCV) infection have used surrogate measures of IR that have limited reliability. We aimed to describe the distribution and risk factors associated with IR and its change over time in HCV using direct measurement.
One hundred two non-cirrhotic, non-diabetic, HCV-infected subjects underwent clinical, histologic, and metabolic evaluation, and 27 completed repeat evaluation at 6 months. Insulin-mediated glucose uptake was measured by steady-state plasma glucose (SSPG) concentration during the insulin suppression test.
Three subjects with diabetes were excluded and 95 completed all testing. SSPG ranged from 39 to 328 mg/dL (mean 135 mg/dL) and was stable over time (mean SSPG change −0.3 mg/dL). SSPG was associated with Latino ethnicity (Coef 67, 95 % CI 37–96), BMI (Coef 19 per 5 kg/m2, 95 % CI 5–32), ferritin (Coef 1.4 per 10 ng/ml, 95 % CI 0.2–2.5), male gender (Coef −48, 95 % CI −80 to −16), and HDL (Coef −16, 95 % CI −28 to −5 mg/dL). Current tobacco use (Coef 55, 95 % CI 19–90), steatosis (Coef −44, 95 % CI −86 to −3), and increases in BMI (Coef 30 per 5 kg/m2, 95 % CI 6–53) and triglyceride (Coef 3.5 per 10 mg/dL, 95 % CI 0.3–6.7) predicted change in SSPG.
There was a wide spectrum of insulin resistance in our HCV population. Host factors, rather than viral factors, appeared to more greatly influence insulin action and its change in HCV.
- Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med. 1999;341:556–562. CrossRef
- DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004;88:787–835, ix.
- Facchini FS, Hua N, Abbasi F, Reaven GM. Insulin resistance as a predictor of age-related diseases. J Clin Endocrinol Metab. 2001;86:3574–3578. CrossRef
- Yip J, Facchini FS, Reaven GM. Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab. 1998;83:2773–2776. CrossRef
- Grasso A, Malfatti F, De Leo P, 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;51:984–990. CrossRef
- Petta S, Camma C, Di Marco V, et al. Insulin resistance and diabetes increase fibrosis in the liver of patients with genotype 1 HCV infection. Am J Gastroenterol. 2008;103:1136–1144. CrossRef
- Romero-Gomez M, Del Mar Viloria M, Andrade RJ, et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005;128:636–641. CrossRef
- 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;54:1003–1008. CrossRef
- Moucari R, Asselah T, Cazals-Hatem D, et al. Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. 2008;134:416–423. CrossRef
- Hui JM, Sud A, Farrell GC, et al. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected]. Gastroenterology. 2003;125:1695–1704. CrossRef
- 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;10:349–355. CrossRef
- Lam KD, Bacchetti P, Abbasi F, et al. Comparison of surrogate and direct measurement of insulin resistance in chronic hepatitis C virus infection: impact of obesity and ethnicity. Hepatology. 2010;52:38–46. CrossRef
- Yeni-Komshian H, Carantoni M, Abbasi F, Reaven GM. Relationship between several surrogate estimates of insulin resistance and quantification of insulin-mediated glucose disposal in 490 healthy nondiabetic volunteers. Diabetes Care. 2000;23:171–175. CrossRef
- Greenfield MS, Doberne L, Kraemer F, Tobey T, Reaven G. Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp. Diabetes. 1981;30:387–392. CrossRef
- Vanni E, Abate ML, Gentilcore E, et al. Sites and mechanisms of insulin resistance in nonobese, nondiabetic patients with chronic hepatitis C. Hepatology. 2009;50:697–706. CrossRef
- Milner KL, van der Poorten D, Trenell M, et al. Chronic hepatitis C is associated with peripheral rather than hepatic insulin resistance. Gastroenterology. 2010;138:932–941, e1–3. CrossRef
- Brandman D, Bacchetti P, Ayala CE, Maher JJ, Khalili M. Impact of insulin resistance on HCV treatment response and impact of HCV treatment on insulin sensitivity using direct measurements of insulin action. Diabetes Care. 2012;35:1090–1094. CrossRef
- Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003;26:S5–S20.
- Marchesini G, Bianchi GP, Forlani G, et al. Insulin resistance is the main determinant of impaired glucose tolerance in patients with liver cirrhosis. Dig Dis Sci. 1987;32:1118–1124. CrossRef
- Letiexhe MR, Scheen AJ, Gerard PL, et al. Insulin secretion, clearance, and action on glucose metabolism in cirrhotic patients. J Clin Endocrinol Metab. 1993;77:1263–1268. CrossRef
- Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995;19:1409–1417. CrossRef
- McLaughlin T, Deng A, Gonzales O, et al. Insulin resistance is associated with a modest increase in inflammation in subcutaneous adipose tissue of moderately obese women. Diabetologia. 2008;51:2303–2308. CrossRef
- Shintani Y, Fujie H, Miyoshi H, et al. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology. 2004;126:840–848. CrossRef
- 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;38:1384–1392.
- Kawaguchi T, Yoshida T, Harada M, 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;165:1499–1508. CrossRef
- Imazeki F, Yokosuka O, Fukai K, Kanda T, Kojima H, Saisho H. Prevalence of diabetes mellitus and insulin resistance in patients with chronic hepatitis C: comparison with hepatitis B virus-infected and hepatitis C virus-cleared patients. Liver Int. 2008;28:355–362. CrossRef
- Tsochatzis E, Manolakopoulos S, Papatheodoridis GV, et al. Serum HCV RNA levels and HCV genotype do not affect insulin resistance in nondiabetic patients with chronic hepatitis C: a multicentre study. Aliment Pharmacol Ther. 2009;30:947–954. CrossRef
- Yazicioglu G, Isitan F, Altunbas H, et al. Insulin resistance in chronic hepatitis C. Int J Clin Pract. 2004;58:1020–1022. CrossRef
- Carter JS, Pugh JA, Monterrosa A. Non-insulin-dependent diabetes mellitus in minorities in the United States. Ann Intern Med. 1996;125:221–232.
- Cowie CC, Rust KF, Byrd-Holt DD, et al. Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: national health and nutrition examination survey 1999–2002. Diabetes Care. 2006;29:1263–1268. CrossRef
- Furutani M, Nakashima T, Sumida Y, et al. Insulin resistance/beta-cell function and serum ferritin level in non-diabetic patients with hepatitis C virus infection. Liver Int. 2003;23:294–299. CrossRef
- D’Souza RF, Feakins R, Mears L, Sabin CA, Foster GR. Relationship between serum ferritin, hepatic iron staining, diabetes mellitus and fibrosis progression in patients with chronic hepatitis C. Aliment Pharmacol Ther. 2005;21:519–524. CrossRef
- Sumida Y, Kanemasa K, Fukumoto K, Yoshida N, Sakai K. Hepatic iron accumulation may be associated with insulin resistance in patients with chronic hepatitis C. Hepatol Res. 2007;37:932–940. CrossRef
- Facchini F, Humphreys MH, Jeppesen J, Reaven GM. Measurements of insulin-mediated glucose disposal are stable over time. J Clin Endocrinol Metab. 1999;84:1567–1569. CrossRef
- Reaven G, Tsao PS. Insulin resistance and compensatory hyperinsulinemia: the key player between cigarette smoking and cardiovascular disease? J Am Coll Cardiol. 2003;41:1044–1047. CrossRef
- Ryan MC, Fenster FHM, Abbasi F, Reaven GM. Comparison of waist circumference versus body mass index in diagnosing metabolic syndrome and identifying apparently healthy subjects at increased risk of cardiovascular disease. Am J Cardiol. 2008;102:40–46. CrossRef
- Howard BV, Mayer-Davis EJ, Goff D, et al. Relationships between insulin resistance and lipoproteins in nondiabetic African Americans, Hispanics, and non-Hispanic whites: the insulin resistance atherosclerosis study. Metabolism. 1998;47:1174–1179. CrossRef
- Cena H, Fonte ML, Turconi G. Relationship between smoking and metabolic syndrome. Nutr Rev. 2011;69:745–753. CrossRef
- Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120:1640–1645. CrossRef
- Insulin Sensitivity and Variability in Hepatitis C Virus Infection Using Direct Measurement
Digestive Diseases and Sciences
Volume 58, Issue 4 , pp 1141-1148
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Insulin resistance
- Oral glucose tolerance test
- Industry Sectors
- Author Affiliations
- 1. Department of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA
- 2. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA
- 3. Liver Center, University of California San Francisco, San Francisco, CA, USA
- 4. San Francisco General Hospital, University of California, San Francisco, 1001 Potrero Avenue, NH-3D, San Francisco, 94110, CA, USA