We read with great interest the recent letter from Öncül et al. (1) reporting the correlation of serum leptin levels with insulin sensitivity in patients with chronic hepatitis C virus (HCV) infection. Their findings showed that fasting serum insulin levels and serum leptin levels were significantly elevated in patients with chronic HCV infection compared with control subjects and that fasting serum leptin and insulin levels and homeostasis model assessment–estimated insulin sensitivity were correlated in the whole group. Öncül et al. concluded that HCV infection may serve as an additional risk factor for the development of type 2 diabetes due to insulin resistance and hyperleptinemia.

Certainly, insulin resistance plays an important role for the development of type 2 diabetes in patients with chronic HCV infection because levels of fasting serum C-peptide were significantly more elevated in non–insulin-treated diabetic patients with (n = 18) than in those without (n = 72) HCV infection (0.73 ± 0.27 vs. 0.57 ± 0.27 nmol/l; P = 0.0321) who were matched by BMI. The authors should show the correlation of serum leptin levels with insulin sensitivity not in the whole group but only in patients with chronic HCV infection, and should exclude the effect of BMI to demonstrate the correlation of serum leptin levels with insulin sensitivity in patients with chronic HCV infection. Conversely, elevated levels of serum leptin and insulin resistance might be correlated regardless of HCV infection (2). Contrary to the conclusion by Öncül et al., that HCV infection may serve as an additional risk factor for the development of type 2 diabetes due to insulin resistance and hyperleptinemia, there are some reports that leptin reverses insulin resistance (3,4). Elevated levels of serum leptin in patients with chronic HCV infection were compatible with previous data (5), although the reason was not fully determined. The mechanism of insulin resistance in patients with chronic HCV infection may be due to decreased liver carbohydrate metabolism and hypersecretion of insulin-resistant cytokines, such as interleukin-6 (6) and tumor necrosis factor (7), which have been shown to be elevated in patients with chronic HCV infection, most likely as a result of HCV-induced inflammation (8,9).

1.
Öncül O, Top C, Cavuslu T: Correlation of serum leptin levels with insulin sensitivity in patients with chronic hepatitis-C infection (Letter).
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2002
2.
Ruige JB, Dekker JM, Blum WF, Stehouwer CD, Nijpels G, Mooy J, Kostense PJ, Bouter LM, Heine RJ: Leptin and variables of body adiposity, energy balance, and insulin resistance in a population-based study: the Hoorn Study.
Diabetes Care
 
22
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1097
–1104,
1999
3.
Petersen KF, Oral EA, Dufour S, Befroy D, Ariyan C, Yu C, Cline GW, DePaoli AM, Taylor SI, Gorden P, Shulman GI: Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy.
J Clin Invest
 
109
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2002
4.
Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ: Acute stimulation of glucose metabolism in mice by leptin treatment.
Nature
 
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1997
5.
Testa R, Franceschini R, Giannini E, Cataldi A, Botta F, Fasoli A, Tenerelli P, Rolandi E, Barreca T: Serum leptin levels in patients with viral chronic hepatitis or liver cirrhosis.
J Hepatol
 
33
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33
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2000
6.
Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G: Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance.
Am J Physiol Endocrinol Metab
 
280
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E745
–E751,
2001
7.
Bestard JP, Maachi M, Nhieu JT, Jardel C, Bruckert E, Grimaldi A, Robert JJ, Capeau J, Hainque B: Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro.
J Clin Endocrinol Metab
 
87
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2084
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2002
8.
Malaguarnera M, Di Fazio I, Romeo MA, Restuccia S, Laurino A, Trovato BA: Elevation of interleukin 6 levels in patients with chronic hepatitis due to hepatitis C virus.
J Gastroenterol
 
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9.
Nelson DR, Lim HL, Marousis CG, Fang JW, Davis GL, Shen L, Urdea MS, Kolberg JA, Lau JY: Activation of tumor necrosis factor-alpha system in chronic hepatitis C virus infection.
Dig Dis Sci
 
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1997

Address correspondence to Michiaki Fukui, First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan. E-mail: [email protected].

DIABETES CARE
2002