Top

Diabetologia

Published in:

01-03-2008 | Article

Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients

Authors: G. Targher, L. Bertolini, S. Rodella, G. Zoppini, G. Lippi, C. Day, M. Muggeo

Published in: Diabetologia | Issue 3/2008

Abstract

Aims/hypothesis

Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease in type 2 diabetes. Currently, there is a lack of information on associations between NAFLD and microvascular complications of diabetes. We assessed the associations between NAFLD and both chronic kidney disease (CKD) and retinopathy in a large cohort of type 2 diabetic individuals using a cross-sectional design.

Methods

Prevalence rates of retinopathy (by ophthalmoscopy) and CKD (defined as overt proteinuria and/or estimated GFR ≤60 ml min⁻¹ 1.73 m⁻²) were assessed in 2,103 type 2 diabetic individuals who were free of diagnosed cardiovascular disease and viral hepatitis. NAFLD was ascertained by patient history, blood sampling and liver ultrasound.

Results

NAFLD patients had higher (p < 0.001) age- and sex-adjusted prevalence rates of both non-proliferative (39 vs 34%) and proliferative/laser-treated retinopathy (11 vs 5%), and CKD (15 vs 9%) than counterparts without NAFLD. In logistic regression analysis, NAFLD was associated with increased rates of CKD (odds ratio 1.87; 95% CI 1.3–4.1, p = 0.020) and proliferative/laser-treated retinopathy (odds ratio 1.75; 1.1–3.7, p = 0.031) independently of age, sex, BMI, waist circumference, hypertension, diabetes duration, HbA_1c, lipids, smoking status and medications use.

Conclusions/interpretation

Our findings suggest that NAFLD is associated with an increased prevalence of CKD and proliferative/laser-treated retinopathy in type 2 diabetic individuals independently of numerous baseline confounding factors. Further studies are required to confirm the reproducibility of these results and to evaluate whether NAFLD contributes to the development or progression of CKD and retinopathy.

Adams LA, Angulo P, Lindor KD (2005) Nonalcoholic fatty liver disease. CMAJ 172:899–905PubMed

Day CP (2006) Nonalcoholic fatty liver disease: current concepts and management strategies. Clin Med 6:19–25PubMed

McCullough AJ (2006) Pathophysiology of non-alcoholic steatohepatitis. J Clin Gastroenterol 40 (Suppl 1):S17–S29PubMed

Marchesini G, Marzocchi R, Agostini F, Bugianesi E (2005) Nonalcoholic fatty liver disease and the metabolic syndrome. Curr Opin Lipidol 16:421–427PubMedCrossRef

Clark JM, Brancati FL, Diehl AM (2003) The prevalence and aetiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 98:960–967PubMedCrossRef

Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S (2005) Prevalence of and risk factors for non-alcoholic fatty liver disease: the Dionysos Nutrition and Liver Study. Hepatology 42:44–52PubMedCrossRef

Browning JD, Szczepaniak LS, Dobbins R et al (2004) Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40:1387–1395PubMedCrossRef

Medina J, Fernandez-Salazar LI, Garcia-Buey L, Moreno-Otero R (2004) Approach to the pathogenesis and treatment of non-alcoholic steatohepatitis. Diabetes Care 27:2057–2066PubMedCrossRef

Targher G, Bertolini L, Padovani R et al. (2007) Prevalence of non-alcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 30:1212–1218PubMedCrossRef

10.

Targher G, Bertolini L, Padovani R et al (2006) Increased prevalence of cardiovascular disease among type 2 diabetic patients with non-alcoholic fatty liver disease. Diabet Med 23:403–409PubMedCrossRef

11.

Targher G, Bertolini L, Poli F et al (2005) Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 54:3541–3546PubMedCrossRef

12.

Targher G, Bertolini L, Rodella S et al (2007) Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients. Diabetes Care 30:2119–2121PubMedCrossRef

13.

Targher G, Arcaro G (2007) Nonalcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis 191:235–240PubMedCrossRef

14.

Levey AS, Coresh J, Balk E et al; National Kidney Foundation (2003) National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 139:137–147PubMed

15.

American Diabetes Association (2007) Standards of medical care in diabetes—2007. Diabetes Care 30 (Suppl 1):S4–S41CrossRef

16.

Wilkinson CP, Ferris FL, Klein RE et al; Global Diabetic Retinopathy Project Group (2003) Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110:1677–1682PubMedCrossRef

17.

Targher G, Bertolini L, Zoppini G, Lippi G, Zenari L (2007) Diabetic retinopathy predicts cardiovascular mortality in type 2 diabetic men and women: response to Juutilainen et al. [Letter]. Diabetes Care 30:e51PubMedCrossRef

18.

Saadeh S, Younossi ZM, Remer EM et al (2002) The utility of radiological imaging in non-alcoholic fatty liver disease. Gastroenterology 123:745–750PubMedCrossRef

19.

Targher G, Bertolini L, Padovani R, Zenari L, Zoppini G, Falezza G (2004) Relation of non-alcoholic hepatic steatosis to early carotid atherosclerosis in healthy men. Role of visceral fat accumulation. Diabetes Care 27:1498–1500

20.

Ryu S, Chang Y, Kim DI, Kim WS, Suh BS (2007) Gamma-glutamyltransferase as a predictor of chronic kidney disease in nonhypertensive and nondiabetic Korean men. Clin Chem 53:71–77PubMedCrossRef

21.

Ratziu V, Imbert-Bismut F, Messous D, Poynard T (2004) The elusiveness of “normal” ALT in fatty liver. Hepatology 39:1172PubMedCrossRef

22.

Belfort R, Harrison SA, Brown K et al (2006) A placebo-controlled trial of pioglitazone in subjects with non-alcoholic steatohepatitis. N Engl J Med 355:2297–2307PubMedCrossRef

23.

Alessi MC, Bastelica D, Mavri A et al (2003) Plasma PAI-1 levels are more strongly related to liver steatosis than to adipose tissue accumulation. Arterioscler Thromb Vasc Biol 23:1262–1268PubMedCrossRef

24.

Targher G, Bertolini L, Scala L et al (2007) Plasma PAI-1 levels are increased in patients with non-alcoholic steatohepatitis. Diabetes Care 30:e31–e32PubMedCrossRef

25.

Targher G (2006) Relationship between high-sensitivity C-reactive protein levels and liver histology in subjects with non-alcoholic fatty liver disease. J Hepatol 45:879–881PubMedCrossRef

26.

Targher G, Bertolini L, Padovani R, Rodella S, Arcaro G, Day C (2007) Differences and similarities in early atherosclerosis between patients with non-alcoholic steatohepatitis and chronic hepatitis B and C. J Hepatol 46:1126–1132PubMedCrossRef

27.

Brownlee M (2005) The pathobiology of diabetic complications. Diabetes 54:1615–1625PubMedCrossRef

28.

Horiuchi S (2002) The liver is the main site for metabolism of circulating advanced glycation end products. J Hepatol 36:123–125PubMedCrossRef

29.

Abiru S, Migita K, Maeda Y et al (2006) Serum cytokine and soluble cytokine receptor levels in patients with non-alcoholic steatohepatitis. Liver Int 26:39–45PubMedCrossRef

30.

Holt HB, Wild SH, Wood PJ et al (2006) Non-esterified fatty acid concentrations are independently associated with hepatic steatosis in obese subjects. Diabetologia 49:141–148PubMedCrossRef

31.

Chalasani N, Deeg MA, Crabb DW (2004) Systemic levels of lipid peroxidation and its metabolic and dietary correlates in patients with non-alcoholic steatohepatitis. Am J Gastroenterol 99:1497–1502PubMedCrossRef

32.

Albano E, Mottaran E, Vidali M et al (2005) Immune response towards lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease to advanced fibrosis. Gut 54:987–993PubMedCrossRef

33.

Chen AYS, Kong APS, Wong VWS et al (2006) Chronic hepatitis B viral infection independently predicts renal outcome in type 2 diabetic patients. Diabetologia 49:1777–1784CrossRef

34.

Groop PH, Forsblom C, Thomas MC (2005) Mechanisms of disease: pathway-selective insulin resistance and microvascular complications of diabetes. Nat Clin Pract Endocrinol Metab 1:100–110PubMedCrossRef

35.

Sarafidis PA, Ruilope LM (2006) Insulin resistance, hyperinsulinemia, and renal injury: mechanisms and implications. Am J Nephrol 26:232–244PubMedCrossRef

36.

Marshall SM, Flyvbjerg A (2006) Prevention and early detection of vascular complications of diabetes. BMJ 333:475–480PubMedCrossRef

Title: Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients
Authors: G. Targher
L. Bertolini
S. Rodella
G. Zoppini
G. Lippi
C. Day
M. Muggeo
Publication date: 01-03-2008
Publisher: Springer-Verlag
Published in: Diabetologia / Issue 3/2008
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-007-0897-4

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Please log in to get access to this content

Other articles of this Issue 3/2008

Autoantibodies to IA-2β improve diabetes risk assessment in high-risk relatives

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program

USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study

Different contribution of class II HLA in fulminant and typical autoimmune type 1 diabetes mellitus

The association between the IFIH1 locus and type 1 diabetes

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page