Prevalence of non-alcoholic fatty liver disease in urban south Indians in relation to different grades of glucose intolerance and metabolic syndrome

doi:10.1016/j.diabres.2008.11.039

Diabetes Research and Clinical Practice

Volume 84, Issue 1, April 2009, Pages 84-91

https://doi.org/10.1016/j.diabres.2008.11.039 Get rights and content

Abstract

Aim

To estimate prevalence of non-alcoholic fatty liver disease (NAFLD) and its association with glucose intolerance (type 2 diabetes (DM), prediabetes) and metabolic syndrome (MS) in urban south Indians.

Methods

This study was carried out in 541 subjects (response rate 92%) of the original sample of 26,001 subjects in the Chennai Urban Rural Epidemiology Study maintaining the representativeness. Anthropometry and lipid estimations were done in all and oral glucose tolerance test in all, except self-reported diabetic subjects. NAFLD was diagnosed by ultrasonography and MS by modified Adult Treatment Panel III (ATP III) criteria. DM, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were defined using WHO consulting group criteria.

Results

Overall prevalence of NAFLD was 32% (173/541 subjects) (men: 35.1%, women: 29.1%, p = 0.140). Prevalence of most cardio-metabolic risk factors was significantly higher in NAFLD subjects. Prevalence of NAFLD (54.5%) was higher in subjects with DM compared to those with prediabetes (IGT or IFG) (33%), isolated IGT (32.4%), isolated IFG (27.3%) and normal glucose tolerance (NGT) (22.5%) (DM vs. prediabetes: p < 0.05, DM vs. NGT: p < 0.001, prediabetes vs. NGT: p < 0.05). Even after adjusting for age, gender and waist circumference, NAFLD was associated with diabetes (OR: 2.9, 95% C.I.: 1.9–4.6, p < 0.001) and MS (OR: 2.0, 95% C.I.: 1.3–3.1, p < 0.001).

Conclusion

NAFLD is present in a third of urban Asian Indians and its prevalence increases with increasing severity of glucose intolerance and in MS. This is the first population-based prevalence of NAFLD from south Asia which faces the brunt of the diabetes epidemic.

Introduction

Non-alcoholic steatohepatitis (NASH) is a type of metabolic liver disease in which fatty change (steatosis) is associated with lobular inflammation, hepatocytic injury and/or hepatic fibrosis and not etiologically associated with alcohol abuse. Non-alcoholic fatty liver disease (NAFLD) is a term used to describe the broader spectrum of the disease that extends from steatosis to “cryptogenic cirrhosis” [1], [2], [3], [4]. The pathophysiological mechanisms underlying NAFLD are poorly understood although a close link with the ‘metabolic syndrome’ characterized by obesity, glucose intolerance, insulin resistance, hyperlipidemia and hypertension is well recognized [1], [2], [3], [4], [5]. Evaluation of liver histology by liver biopsy is undoubtedly the diagnostic test for fatty liver; however due to the attendant risks, expense and uncertain benefit to asymptomatic patients it is not applicable to population-based studies. Serum liver enzymes have been used in some studies although they are neither sensitive nor specific for NAFLD. Ultrasound of the liver although insensitive to pick up steatosis of less than 25–30%, is often used in epidemiological studies due its lower cost and lack of risk.

Although in the general population, the prevalence of NAFLD and NASH are approximately 20% and 3% respectively [6], [7], in obese populations, NAFLD may be present in 75% of subjects [8]. Indeed, in the morbidly obese, steatosis (NAFLD) has been found in almost all subjects [9], with NASH being present in 25–70% of these individuals [9], [10]. However, these studies were mainly done in western populations. South Asians (people belonging to India, Pakistan, Bangladesh, Nepal, Sri Lanka and Malaysia) in general and Asian Indians in particular, have very high rates of diabetes [11], insulin resistance [12], [13] and premature CAD [14]. Moreover, a recent clinic-based study suggests differences in the clinicopathological profile of Indian patients with NAFLD [15]. Thus, the current study was undertaken to establish the prevalence of NAFLD in a representative sample of an urban south Indian population and study its association with glucose intolerance and metabolic syndrome, as there is no population-based data from south Asia on NAFLD.

Section snippets

Methodology

The Chennai Urban Rural Epidemiology Study (CURES) is a large cross-sectional study done on a representative population of metropolitan city of Chennai (formerly Madras) in southern India with a population of about 5 million people. The detailed study design of CURES is described elsewhere [16] and the sampling frame is shown in our website http://www.drmohansdiabetes.com/bio/WORLD/pages/pages/chennai.html. Briefly, of the 155 Corporation wards in Chennai, 46 wards were randomly selected across

Definitions

Body mass index (BMI) was calculated using the formula: weight (kg)/height (m)².

Waist circumference: Waist was measured using a non-stretchable fibre measuring tape. The subjects were asked to stand erect in a relaxed position with both feet together on a flat surface. Waist girth was measured as the smallest horizontal girth between the costal margins and the iliac crests at minimal respiration. Two measurements were made and the mean of the two was taken as the waist circumference.

Blood

Statistics

Statistical analyses were performed using SPSS for window version 10.0 software (SPSS Inc., Chicago, IL). Values are expressed as the means ± S.D. Student's t-test or one-way ANOVA, as appropriate, was used to compare continuous variables, and the χ²-test was used to compare proportions among groups. p-Value <0.05 was considered significant. Due to their skewed distribution, serum triglycerides and insulin resistance were transformed to natural logarithms and the values were expressed as median

Results

The overall prevalence of NAFLD in the population was 32% (173/541 subjects) (men: 35.1% and women: 29.1%, p = 0.140). Table 1 shows the general characteristics of the study subjects. Subjects with NAFLD were older and had significantly higher BMI, waist and hip circumference, systolic and diastolic blood pressure, fasting plasma glucose, HbA1c, total cholesterol, triglycerides, alanine aminotransferase, alkaline phosphatase, fasting insulin and HOMA-IR and lower HDL cholesterol values compared

Discussion

There are very few population-based studies on the prevalence of NAFLD in the general population as the majority of studies are in subjects with type 2 diabetes or in obesity. This study is the first, to our knowledge, to report on the prevalence of NAFLD in a south Asian population. This study makes the following points: (i) the prevalence of NAFLD was 32% among the urban general population and its prevalence increased with increasing severity of glucose intolerance; (ii) NAFLD was strongly

Conflict of interest

There are no conflicts of interest.

Acknowledgements

We are grateful to the Chennai Willingdon Corporate Foundation, Chennai for the financial support provided for the study. We thank the epidemiology team members for conducting the CURES field studies. This is the 56th publication from CURES (CURES–56).

References (48)

A.M. Diehl et al.
Alcoholic disease in nonalcoholics: a clinical and histologic comparison with alcohol-induced liver injury
Gastroenterology
(1988)
C.A. Matteoni et al.
Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity
Gastroenterology
(1999)
K.R. Falchuk et al.
Pericentral hepatic fibrosis and intracellular hyaline in diabetes mellitus
Gastroenterology
(1980)
S.S. Anand et al.
Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic Groups (SHARE)
Lancet
(2000)
A.E. Joseph et al.
Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease
Clin. Radiol.
(1991)
B.A. Neuschwander-Tetri et al.
Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference
Hepatology
(2003)
G. Bedogni et al.
Fatty liver: how frequent is it and why?
Ann. Hepatol.
(2004)
V. Ratziu et al.
Liver fibrosis in overweight patients
Gastroenterology
(2000)
B.R. Bacon et al.
Nonalcoholic steatohepatitis: an expanded clinical entity
Gastroenterology
(1994)
R.G. Lee
Nonalcoholic steatohepatitis: a study of 49 patients
Hum. Path.
(1989)

G. Marchesini et al.

Association of nonalcoholic fatty liver disease with insulin resistance

Am. J. Med.

(1999)

H. Cortez-Pinto et al.

Non-alcoholic fatty liver: another feature of the metabolic syndrome?

Clin. Nutr.

(1999)

A.J. Sanyal et al.

Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities

Gastroenterology

(2001)

V. Mohan et al.

Prevalence of coronary artery disease and its relationship to lipids in a selected population in south India. The Chennai Urban Population Study (CUPS No. 5)

J. Am. Coll. Cardiol.

(2001)

J.A. Marrero et al.

NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States

Hepatology

(2002)

E. Bugianesi et al.

Expanding the natural history of non-alcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma

Gastroenterology

(2002)

P. Angulo

Nonalcoholic fatty liver disease

N. Engl. J. Med.

(2002)

G.C. Farrel et al.

Overview: an introduction to NASH and related fatty liver disorders

E.M. Brunt

Nonalcoholic steatohepatitis

Semin. Liver Dis.

(2004)

J. Ludwig et al.

Nonalcoholic steatohepatitis: Mayo Clinic experience with a hitherto unnamed disease

Mayo Clin. Proc.

(1980)

B.P. Mulhall et al.

Non-alcoholic fatty liver disease: an overview

J. Gastroenterol. Hepatol.

(2002)

S. Itoh et al.

Comparison between non-alcoholic steatohepatitis and alcoholic hepatitis

Am. J. Gastroenterol.

(1987)

S.G. Sheth et al.

Nonalcoholic steatohepatitis

Ann. Intern. Med.

(1997)

S. Wild et al.

Global prevalence of diabetes, estimates for the year 2000 and projections for 2030

Diabet. Care

(2004)

Cited by (158)

Prevalence of nonalcoholic fatty liver disease in type 2 diabetes mellitus patients from the Eastern region of India
2023, Diabetes Epidemiology and Management
The risk of nonalcoholic fatty liver disease (NAFLD) is increased significantly in individuals having Type 2 diabetes mellitus (T2DM) and the presence of T2DM enormously drives NAFLD progression. However, in clinical practice, it is overlooked despite the significant clinical effects of NAFLD in T2DM. Our study aimed to estimate the prevalence of NAFLD in T2DM patients from the eastern region of India.
This cross-sectional study assessed 132 T2DM patients for NAFLD. Anthropometry and lipid estimations were done in all the individuals. Hepatic fibrosis was diagnosed by transient elastography (TE) using a TOUCH 502 Fiber Scanner using M‑probe. A fibrosis score ≥ 11 kgpascals (kPa) was used to define advanced fibrosis (F3).
Overall prevalence of NAFLD in T2DM patients was 57% (75/132 subjects) and the prevalence is higher in males (54.6%). Results showed that approximately 26% of patients with NAFLD will develop into NASH, among them 37.3% developed mild to moderate steatosis and 26.6% developed severe steatosis.
The prevalence of NAFLD is high in the eastern region of India, need for early diagnosis and treatment of NAFLD in T2DM. The use of TE with other serum markers can be helpful for the diagnosis of advanced fibrosis.
Prevalence and associated factors for non-alcoholic fatty liver disease among adults in the South Asian Region: a meta-analysis
2023, The Lancet Regional Health - Southeast Asia
Non-alcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease worldwide. We estimated the prevalence and predefined associated factors for NAFLD among South-Asian adults.
We searched PubMed and included descriptive, epidemiological studies with satisfactory methodology, reporting the prevalence of NAFLD with ultrasound. Two authors screened and extracted data independently. Gender, urban/rural settings, general population and individuals with metabolic diseases (MetD) stratified the analysis. In addition, a random-effects meta-analysis of the prevalence and effect sizes of associations of NAFLD was performed.
Twenty-two publications were included after the quality assurance process. The difference in the NAFLD prevalence between the general population and people with MetD was found to be statistically significant (Q = 15.8, DF = 1, P < 0.001). The pooled overall prevalence of NAFLD in the general population was 26.9% (95% CI: 18.9–35.8%) with high heterogeneity. The prevalence was similar among men and women (Q = 0.06, DF = 1, P = 0.806). The NAFLD prevalence in the rural communities was 22.6% (95% CI: 13.6–33.1%), and the prevalence in urban communities was 32.9% (95% CI: 22.8–43.8%) and the difference was not statistically significant (Q = 1.92, DF = 1, P = 0.166). The pooled overall prevalence of NAFLD in patients with MetD was 54.1% (95% CI: 44.1–63.9%) with high heterogeneity. The pooled overall prevalence of NAFLD in the non-obese population was 11.7% (95% CI: 7.0–17.3%). The pooled prevalence of non-obese NAFLD in the NAFLD population was 43.4% (95% CI: 28.1–59.4%). Meta-analysis of binary variables showed that NAFLD in the South Asian population was associated with diabetes mellitus, hypertension, dyslipidaemia, general obesity, central obesity and metabolic syndrome. Gender was not associated with NAFLD.
The overall prevalence of NAFLD among adults in South Asia is high, especially in those with MetD, and a considerable proportion is non-obese. In the South Asian population, NAFLD was associated with diabetes mellitus, hypertension, dyslipidaemia, general obesity, central obesity, and metabolic syndrome.
None.
Liver Stiffness Values in Persons with Normal Histology
2023, Journal of Clinical and Experimental Hepatology
Citation Excerpt :
NAFLD is commonly associated with obesity but can occur in lean patients also.11,12 NAFLD is very common in India with a prevalence in urban Indians ranging from 16% to 53%.13–16 The prevalence is higher in patients with type 2 diabetes.17,18
Most studies to date have focused on liver stiffness measurement (LSM) in patients with different chronic liver diseases, and normal LSM is defined based on normal liver function tests or the absence of fibrosis. Very few studies have defined LSM based on completely normal liver biopsies. The current study was done to define the distribution of LSM values in individuals with normal liver biopsies.
All prospective liver donors presenting to Medanta, the Medicity hospital between September 2020 and September 2021 fulfilling the eligibility criteria were included in this study.
A total of 63 donors (36 females and 27 males) were included in the study, 37 (58.7%) donors had normal liver biopsies, and 26 (41.2%) donors showed the presence of non-alcoholic fatty liver disease. LSM values in the normal liver histology group were 5.01 ± 1.99 kPa by the M probe and 5.34 ± 2.25 kPa by the XL probe. Even though the correlation was weak (r = 0.29, P = 0.03), M probe LSM correlated positively with body mass index. There was a good correlation between the LSM measured by the M probe and the XL probe (r = 0.73, P = <0.001).
LSM value in the biopsy-proven normal liver histology group was 5.01 ± 1.99 by the M probe and 5.34 ± 2.25 by the XL probe.
2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis
2022, Clinical Gastroenterology and Hepatology
The increasing rates of obesity and type 2 diabetes mellitus may lead to increased prevalence of nonalcoholic fatty liver disease (NAFLD). We aimed to determine the current and recent trends on the global and regional prevalence of NAFLD.
Systematic search from inception to March 26, 2020 was performed without language restrictions. Two authors independently performed screening and data extraction. We performed meta-regression to determine trends in NAFLD prevalence.
We identified 17,244 articles from literature search and included 245 eligible studies involving 5,399,254 individuals. The pooled global prevalence of NAFLD was 29.8% (95% confidence interval [CI], 28.6%–31.1%); of these, 82.5% of included articles used ultrasound to diagnose NAFLD, with prevalence of 30.6% (95% CI, 29.2%–32.0%). South America (3 studies, 5716 individuals) and North America (4 studies, 18,236 individuals) had the highest NAFLD prevalence at 35.7% (95% CI, 34.0%–37.5%) and 35.3% (95% CI, 25.4%–45.9%), respectively. From 1991 to 2019, trend analysis showed NAFLD increased from 21.9% to 37.3% (yearly increase of 0.7%, P < .0001), with South America showing the most rapid change of 2.7% per year, followed by Europe at 1.1%.
Despite regional variation, the global prevalence of NAFLD is increasing overall. Policy makers must work toward reversing the current trends by increasing awareness of NAFLD and promoting healthy lifestyle environments.
Prevalence of Non-alcoholic Fatty Liver Disease in India: A Systematic Review and Meta-analysis
2022, Journal of Clinical and Experimental Hepatology
Citation Excerpt :
Subgroup analyses were performed for age group, gender, risk category, and urban/rural populations. The literature search identified 50 studies5,9–12,14,15,20–62 (Figure 1, PRISMA flow chart) which provided NAFLD prevalence among children (n = 8) and adults (n = 54). The characteristics of the included studies are summarized in Table 1.
Non-alcoholic fatty liver disease (NAFLD) contributes to a large proportion of liver disease burden in the world. Several groups have studied the prevalence of NAFLD in the Indian population.
A systematic review of the published literature and meta-analysis was carried out to estimate the prevalence of NAFLD in the Indian population.
English language literature published until April 2021 was searched from electronic databases. Original data published in any form which had reported NAFLD prevalence in the Indian population were included. The subgroup analysis of prevalence was done based on the age (adults or children) and risk category, i.e., average-risk group (community population, participants of control arm, unselected participants, hypothyroidic individuals, athletes, aviation crew, and army personnel) and high-risk group (obesity or overweight, diabetes mellitus, coronary artery disease, etc.). The prevalence estimates were pooled using the random-effects model. Heterogeneity was assessed with I².
Sixty-two datasets (children 8 and adults 54) from 50 studies were included. The pooled prevalence of NAFLD was estimated from 2903 children and 23,581 adult participants. Among adults, the estimated pooled prevalence was 38.6% (95% CI 32–45.5). The NAFLD prevalence in average-risk and high-risk subgroups was estimated to be 28.1% (95% CI 20.8–36) and 52.8% (95% CI 46.5–59.1), respectively. The estimated NAFLD prevalence was higher in hospital-based data (40.8% [95% CI 32.6–49.3%]) than community-based data (28.2% [95% CI 16.9–41%]). Among children, the estimated pooled prevalence was 35.4% (95% CI 18.2–54.7). The prevalence among non-obese and obese children was 12.4 (95% CI 4.4–23.5) and 63.4 (95% CI 59.4–67.3), respectively.
Available data suggest that approximately one in three adults or children have NAFLD in India.
Diagnostic Accuracy and Optimal Cut-off of Controlled Attenuation Parameter for the Detection of Hepatic Steatosis in Indian Population
2022, Journal of Clinical and Experimental Hepatology
Ultrasound of the liver is not good to pick up mild steatosis. Controlled attenuation parameter (CAP) evaluated in transient elastography (FibroScan) is widely available in India. However, data regarding the diagnostic accuracy and optimal cut-off values of CAP for diagnosing hepatic steatosis are scarce in Indian population. MRI-PDFF is an accurate technique for quantifying hepatic steatosis. Thus, this study examined the diagnostic accuracy and optimal cut-off values of CAP for diagnosing steatosis with MRI-PDFF as reference standard.
A total of 137 adults underwent CAP and MRI-PDFF measurements prospectively. A subset of participants (n = 23) underwent liver biopsy as part of liver transplantation evaluation. The optimal cut-off values, area under the receiver operating characteristic (AUROC) curves, sensitivity, and specificity for CAP in detecting MRI-PDFF ≥5% and ≥10% were assessed.
The mean age and body mass index (BMI) were 44.2 ±10.4 years and 28.3 ±3.9 kg/m², respectively. The mean hepatic steatosis was 13.0 ±7.7% by MRI-PDFF and 303 ±54 dB/m by CAP. The AUROC of CAP for detecting hepatic steatosis (MRI-PDFF ≥5%) was 0.93 (95% CI, 0.88–0.98) at the cut-off of 262 dB/m, and of MRI-PDFF ≥10% was 0.89 (95% CI, 0.84–0.94) at the cut-off of 295 dB/m. The CAP of 262 dB/m had 90% sensitivity and 91% specificity for detecting MRI-PDFF ≥5%, while the CAP of 295 dB/m had 86% sensitivity and 77% specificity for detecting MRI-PDFF ≥10%.
The optimal cut-off of CAP for the presence of liver steatosis (MRI-PDFF ≥5%) was 262 dB/m in Indian individuals. This CAP cut-off was associated with good sensitivity and specificity to pick up mild steatosis.

View all citing articles on Scopus

View full text

Prevalence of non-alcoholic fatty liver disease in urban south Indians in relation to different grades of glucose intolerance and metabolic syndrome

Abstract

Aim

Methods

Results

Conclusion

Introduction

Section snippets

Methodology

Definitions

Statistics

Results

Discussion

Conflict of interest

Acknowledgements

Gastroenterology

Gastroenterology

Gastroenterology

Lancet

Clin. Radiol.

Hepatology

Ann. Hepatol.

Gastroenterology

Gastroenterology

Hum. Path.

Am. J. Med.

Clin. Nutr.

Gastroenterology

J. Am. Coll. Cardiol.

Hepatology

Gastroenterology

Nonalcoholic fatty liver disease

N. Engl. J. Med.

Overview: an introduction to NASH and related fatty liver disorders

Nonalcoholic steatohepatitis

Semin. Liver Dis.

Nonalcoholic steatohepatitis: Mayo Clinic experience with a hitherto unnamed disease

Mayo Clin. Proc.

Non-alcoholic fatty liver disease: an overview

J. Gastroenterol. Hepatol.

Comparison between non-alcoholic steatohepatitis and alcoholic hepatitis

Am. J. Gastroenterol.

Nonalcoholic steatohepatitis

Ann. Intern. Med.

Global prevalence of diabetes, estimates for the year 2000 and projections for 2030

Diabet. Care