• Users Online: 103
  • Print this page
  • Email this page


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 8  |  Issue : 3  |  Page : 68-73

Glucose intolerance and insulin resistance in non-alcoholic fatty liver disease: A Hospital-based Cross-sectional Study from Southern Karnataka, India


1 Department of Medicine, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
2 Department of Statistics, Manipal University, Manipal, Karnataka, India

Date of Web Publication29-Dec-2017

Correspondence Address:
Sudha Vidyasagar
Department of Medicine, Kasturba Medical College, Manipal University, Udupi, Manipal - 576 104, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jod.jod_12_17

Rights and Permissions
  Abstract 


Context: Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance (IR) and glucose intolerance. Indian data in this area are sparse, and hence, we undertook this study to find the relationship between NAFLD and diabetes. Objective: The objective of this study is to find the relationship between NAFLD and various levels of glucose intolerance and IR. Settings and Design: A cross-sectional study on 150 patients aged 18 or above and diagnosed to have NAFLD by ultrasonography from October 2013 to June 2015 who were admitted or outpatients in the Department of General Medicine, Kasturba Medical College, Manipal. Methodology: NAFLD was graded as mild, moderate or severe by a single radiologist using high-resolution B-mode ultrasonography system. Basic anthropometric, clinical examination and relevant biochemical investigations were done for all patients. Glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and post-load plasma glucose (PG) were measured in all subjects, fasting insulin levels were measured in all subjects by chemiluminescence method to determine IR and it was calculated using homeostasis model assessment model. Statistical Analysis Used: Data were analysed using SPSS software version 15 and P < 0.05 considered as statistically significant. Results: The percentage of pre-diabetes and diabetes in NAFLD patients were 52.7% and 30.7% respectively, There was a greater proportion of pre-diabetics and diabetics in the higher grades of NAFLD (P < 0.001). We observed mean FPG, PG and HbA1c levels increased as the severity of NAFLD increased in this study. The overall mean HOMA-IR score in our subjects was found to be 4.68 ± 2.81 and 76.7% of patients had IR was significantly (P < 0.001) higher in Grade 2 and Grade 3 NAFLD. Conclusions: There is a high prevalence of pre-diabetes and diabetes in patients with NAFLD, and this is associated with increasing IR in higher grades of NAFLD.

Keywords: Insulin resistance, non-alcoholic fatty liver disease, type 2 diabetes


How to cite this article:
Mathew T, Vidyasagar S, Varma MD, Nandakrishna B, Holla AM, Binu V S. Glucose intolerance and insulin resistance in non-alcoholic fatty liver disease: A Hospital-based Cross-sectional Study from Southern Karnataka, India. J Diabetol 2017;8:68-73

How to cite this URL:
Mathew T, Vidyasagar S, Varma MD, Nandakrishna B, Holla AM, Binu V S. Glucose intolerance and insulin resistance in non-alcoholic fatty liver disease: A Hospital-based Cross-sectional Study from Southern Karnataka, India. J Diabetol [serial online] 2017 [cited 2018 Apr 26];8:68-73. Available from: http://www.journalofdiabetology.org/text.asp?2017/8/3/68/222083




  Introduction Top


Non-alcoholic fatty liver disease (NAFLD) which is characterised by an accumulation of fat in the liver with little or no alcohol consumption is the most common cause of liver disease worldwide.[1] The prevalence estimates of NAFLD ranges from 25% to 45% in most studies.[2] The community prevalence of NAFLD in India varies from 5% to 28%.[3],[4],[5] Mohan et al. found 32% prevalence of NAFLD in the urban population of Chennai in 2009 using ultrasonography (USG).[6]

NAFLD is typically associated with central obesity, diabetes, hypertension, dyslipidaemia and metabolic syndrome.[7] Insulin resistance (IR) promotes the fatty acid accumulation and oxidative stress [8] and plays a key role in disease progression in the liver. Further, NAFLD is also known to contribute to glucose intolerance making this a vicious cycle. In India the prevalence of pre-diabetes and diabetes in NAFLD has been found to be variable from 33% to 64%.[6],[9],[10] Hence, we consider analysing the relationship between these two disorders in a south Indian rural population. This study aims to understand the relationship between various grades of NAFLD and level of glucose intolerance as well as IR.


  Methodology Top


This cross-sectional study was initiated after obtaining clearance from the Ethical Committee of Kasturba Medical College (KMC), Manipal, Karnataka, India (IEC No: 508/2013). Patients aged 18 or above and diagnosed to have NAFLD by USG from October 2013 to June 2015 who were admitted or outpatients in the Department of General Medicine, KMC Manipal, after obtaining written informed consent were included. Relevant history regarding alcohol consumption and intake of hepatotoxic drug such as antituberculosis treatment was elicited and excluded. Hepatitis B and C screening was done in all patients to exclude other significant hepatic condition.

Sample size was calculated according to formula:



Where n stands for sample size, Zα stands for 95% percentile value of a standard normal distribution, P stands for anticipated prevalence, d stands for absolute precision.

With anticipated prevalence of 55% and 20% relative precision with 95% confidence interval, minimum sample size was calculated to be 141.

Ultrasound abdomen was performed by a single radiologist using high-resolution B mode ultrasonography system, Phillips IU 22 Machine, using curvilinear 3–5 MHz transducer and if fatty changes were present, it was graded as mild, moderate or severe by the radiologist.

Relevant history regarding alcohol consumption and other major etiologies of liver disease were asked to exclude patients. Basic anthropometric measures were done for 150 eligible patients. Clinical examination and relevant biochemical investigations were done for all patients. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured by ultraviolet with pyridoxal 5'phosphate method using Cobas 6000 auto analyser. Fasting lipid profile was measured including triglycerides (TGs) (GPO grinder method using Roche Cobas E601 analyser machine). The coefficient variation of ALT and AST was 2.36% and 1.50%, respectively; for fasting plasma glucose (FPG) and post-prandial glucose (PPG) were 1.26% and 1.15%, respectively; and for fasting insulin 2.20% and for TG 3.56%.

HbA1c was measured using NGSP certified high-performance liquid chromatography using BioRad Variant Haemoglobin analyser. FPG and PPG were measured using Hexokinase method using Roche Cobas E601 analyser machine. A 2 h oral glucose tolerance test (OGTT) to document impaired glucose tolerance (IGT) was done in patients with FPG in impaired fasting glucose (IFG) range (100–125 mg/dl) or in those with a HbA1c in the pre-diabetic range (5.7–6.4). Hexokinase method using Roche Cobas E601 analyser machine was used.

Fasting insulin levels were measured in all subjects by chemiluminescence using Roche Cobas E601 analyser machine) to determine IR, and it was calculated using Homeostasis Model Assessment Model (HOMA IR = fasting glucose [mg/dl] × fasting insulin [μU/mL] ÷405).

Definitions

Height

Height was measured with the patient standing against an upright surface touching it with heels, buttocks and back on a level smooth surface. The measurement was taken when the subject held the breath in inspiration and unit of measurement was meters.

Weight

Subject-wearing minimal clothing was made to stand in the centre of on an electronic weighing machine. Weight was recorded to the nearest tenth of a kilogram. The same machine was used for calculating the weight for all the subjects who underwent the study.

Body mass index

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

Waist circumference

Waist circumference (WC) was measured midway between inferior margin of ribs and the superior border of iliac crest with a plastic tape (WHO steps protocol).[11] WC of ≥90 cm for males and ≥80 cm for females were considered as abnormal (IDF criteria).[12]

Blood pressure recording

Two measurements under standard conditions were made, and the average was taken as the blood pressure (BP). Raised BP was defined as systolic pressure ≥140 mmHg, diastolic ≥90 mmHg or patient on antihypertensive treatment for previously diagnosed hypertension.

Diabetes

As per ADA criteria, i.e., FPG ≥126 mg/dl or 2 h post-load plasma glucose (2 h PG) ≥200 mg/dl or self-reported diabetic subjects on treatment by a physician.[13]

Impaired glucose tolerance

IGT was diagnosed if the 2 h PG was ≥140 mg/dl and <200 mg/dl and FPG <126 mg/dl.[13]

Impaired fasting glucose

IFG was diagnosed if the FPG was ≥100 mg/dl and <125 mg/dl PPG <140.[13]

  • Isolated IFG: FPG was ≥100 mg/dl and <125 mg/dl with normal PPG <140
  • Isolated IGT: 2 h PG was ≥140 mg/dl and <200 mg/dl with normal fasting glucose <126.


Pre-diabetes

Pre-diabetes was defined as IGT or IFG according to the ADA criteria. Isolated IGT and isolated IFG were also used separately in the analyses.[13]

Obesity

Generalised obesity was defined using the new WHO Asia Pacific guidelines,[14] i.e., body mass index ≥25 kg/m 2 and abdominal obesity as WC ≥90 cm for men and ≥80 cm for women.

NAFLD if present was classified based on standard ultrasonographic criteria as:[15]

  1. Grade 1 fatty liver or mild steatosis: Increased echogenicity of the liver with normal visualisation of a diaphragm and intrahepatic vessels
  2. Grade 2 fatty liver or moderate steatosis: Moderate increase echogenicity leading to impaired visualisation of diaphragm and intrahepatic vessels
  3. Grade 3 fatty liver or severe steatosis: Marked increase in echogenicity with poor visualisation of the posterior structures such as the diaphragm.[15]


Statistical analysis

Data were analysed using SPSS software (SPSS version 15, Chicago, IL, USA). Pearson's Chi-square test was used to study the relation between various categorical variables. Mean (or median) and standard deviation (or 25th percentile, 75th percentiles) values were calculated for continuous variables. One-way ANOVA test was done to study the relation between mean values of the required parameters and various categories of NAFLD.


  Results Top


A total of 150 subjects participated in the study, out of which 76 (50.7%) participants had Grade 1, 55 (36.7%), Grade 2 and 19 (12.7%) and Grade 3 of NAFLD. [Table 1] shows the general characteristics of the study participants. An advanced age, the greater proportion of male subjects, more subjects with obesity and increased WC was observed among higher grades of NAFLD.
Table 1: General characteristics of non.alcoholic fatty liver disease subjects

Click here to view


The WC of >80 cm in female and 90 cm in male considered abnormal. In this study, 73.6% males were having abnormal WC and 95% females were having abnormal WC and also we observed increase in the number of subjects with abnormal WC as severity of NAFLD increases and it was shown in [Figure 1].
Figure 1: Abnormal waist circumference in different grades of non-alcoholic fatty liver disease. In Grade 1 non-alcoholic fatty liver disease 63.2% males and 90% females had abnormal waist circumference while in Grade 2 non-alcoholic fatty liver disease 79.4% males and 95% females had abnormal waist circumference. In Grade 3 non-alcoholic fatty liver disease 86.7% males and 100% females were having abnormal waist circumference

Click here to view


The overall proportion of pre-diabetes and diabetes in NAFLD subjects was observed to be 79 (52.7%) and 46 (30.7%) subjects, respectively. The distribution of glycaemic status of subjects among different grades of NAFLD was shown in [Table 2]. There was a greater proportion of pre-diabetics and diabetics in the higher grades of NAFLD (P < 0.001).
Table 2: Glucose profiles in different grades of non-alcoholic fatty liver disease

Click here to view


Out of 79 pre-diabetics, isolated IFG were seen in 50 (63.2%) participants, 27 (34.1%) participants had both IFG and IGT and only IGT was observed in 2 (2.5%) participants. It was observed that mean FPG, PPG and HbA1c increased with increased severity of NAFLD. The laboratory profiles of glucose intolerance in different grades of NAFLD are shown in [Table 2].

IR was calculated for the subjects by HOMA-IR with the score above 3 denoting IR. The overall median HOMA-IR score in the study participants was found to be 4.12 (3.06, 5.48) and 114 (76.7%) participants had IR and it was significantly (P < 0.001) higher in Grade 2 and Grade 3 NAFLD as shown in [Table 2].

IR was further categorised as normal (HOMA-IR <3), moderate (HOMA-IR 3–5) and severe (HOMA IR >5).[16] Out of 150 study participants, 36 (24%) of them had normal IR while 60 (40%) had moderate and54 (36%) had severe IR. The number of the subjects with severe IR increased significantly (P < 0.001) as increased in severity of NAFLD. Proportion of subjects with different levels of IR in different grades of NAFLD is shown in [Table 3].
Table 3: Different levels of insulin resistance in different grades of non.alcoholic fatty liver disease

Click here to view


In our study, 88 (58.7%) subjects had dyslipidaemia, and this number was significantly higher (P = 0.001) with higher grades of NAFLD as shown in [Table 1]. 24 (16%) subjects had abnormal AST and 26 (17.3%) had abnormal ALT and these elevations between the three groups were not clinically significant. Hence, these turned out to be a poor indicator of the severity of NAFLD.


  Discussion Top


There is a paucity of data from India on the presence of glucose intolerance in NAFLD patients. Apart from a large epidemiological survey conducted by Mohan et al. which documented the prevalence of NAFLD in patients with glucose intolerance (starting from the opposite end of the spectrum), there is no significant data in this area.

In our hospital-based study, we found more patients with Grade 1 NAFLD than Grade 3. The possible explanations for this being that India may be in the initial stages of NAFLD epidemic or the earlier detection of the disease by USG.

NAFLD was found to be more prevalent in males from Indian and other Asian studies. Mahaling et al. in a study from Maharashtra also came up with similar statistics of male preponderance [17],[18] Male gender is also associated with the more severe disease with histological non-alcoholic steatohepatitis, hepatic fibrosis and higher overall mortality.[19],[20] It was also noted that male patients had severe grades of NAFLD as documented by Mohammadi et al.[21] Female hormones may have a protective effect against the disease and it is more common among post-menopausal women than younger age groups. In our study also, there was a higher percentage of males in Grade 3 NAFLD as compared to Grade 2 and 1.

Obesity was more prevalent in Grade 2 and Grade 3 NAFLD as shown in [Table 1]. Kwon et al.[22] and Abangah et al.[23] also found similar results from other parts of the world. In obese individuals, there is increased the supply of free fatty acid (FFA) to the liver from the diet, adipose tissue and also through de novo lipogenesis promoting hepatic steatosis. Due to excess of circulating FFA, an abundance of pro-inflammatory cytokines with a relative or absolute deficiency of anti-inflammatory cytokines, which is governed by the hormonally active adipose tissue.

Our subjects also had significant visceral fat with higher WC in Grade 2 and Grade 3 NAFLD. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) have different expression of adipokines and cytokines. SAT has a predominant expression of leptin and adiponectin whereas VAT predominantly secrets tumor-necrosis factor-alpha and interleukin 6 and 8. VAT may contribute more to IR than SAT due to its cytokine profile.

Type 2 diabetes mellitus (T2DM) and NAFLD are pathophysiologically related. This relationship among T2DM, IR and NAFLD are expected because insulin is subsequently delivered directly to the portal vein after secretion, taking the same route as the absorbed glucose, and the liver eliminates a large portion of portal insulin at the first pass.[24] In our study, 83.3% of our subjects had glucose intolerance of which the majority (52.7%) was pre-diabetic. Moreover, 30% of our patients had overt diabetes. This was in accordance with a western study by Ortiz-Lopez et al.[25] in which 85% of the subjects had abnormal glucose metabolism (pre-diabetes and diabetes). Singh et al.[26] in 2013, also demonstrated a higher glucose intolerance in patients with NAFLD.

Further, we found that there is a direct relationship between glucose intolerance and severity of NAFLD with increasing pre-diabetes and diabetes, as we move from Grade 1 to Grade 3 NAFLD, with Grade 3 having a very high percentage of diabetic patients (78.9%) as shown in [Table 2]. By definition, pre-diabetes and diabetes are states of relative insulin deficiency that, when combined with excess caloric intake and obesity, will commonly contribute to increased portal fatty acids and ectopic fat deposition, including in the liver. In addition, the glucose intolerance may significantly increase the hepatic destruction as shown by Haukeland et al.[27] who opined that T2DM and pre-diabetes are the only predictors for development of steatohepatitis and fibrosis in patients with NAFLD.

In our study group, the majority of the subjects had pre-diabetes which included IFG/IGT/IFG andIGT. In patients having IFG alone (63.2%), about half the number (34.1%) had IFG + IGT which was detected after a standard 75 g OGTT, showing the pre-diabetes tendency throughout the glycaemic range. Yun et al.[28] did OGTT in 48 patients with NAFLD and impaired fasting glucose and found 37.6% to have IGT also. Only 2% of our subjects were found to be having isolated IGT without IFG. The pathophysiology of IFG seems to include the following key defects: reduced hepatic insulin sensitivity, beta cell dysfunction and/or chronic low beta cell mass, altered glucagon-like peptide-1 secretion and inappropriately elevated glucagon secretion. This clearly explains the increased proportion of IFG in this study.[29]

NAFLD is considered the hepatic component of the metabolic syndrome and IR represents its pathophysiological hallmark. IR in NAFLD is characterised by reduced whole-body, hepatic and adipose tissue insulin sensitivity. Hepatic steatosis and IR are considered to be the parts of a vicious cycle both being the cause and effect of the other. Moreover, Asian Indians phenotypes have increased WC and visceral fat which in turn makes them more susceptible to IR.[30]

The majority of study participants, specifically 76.7% had IR and the median HOMA-IR score was 4.12 (3.06, 5.48). In a study by Park et al.,[31] 77.8% of the subjects were found to have IR. The two Indian studies which looked for IR in NAFLD were by Bajaj et al.[32] and Bhat et al.[33] and the prevalence of IR in these studies were 46.15% and 97.5%, respectively. We further classified the subjects into three categories-normal IR, moderate IR and severe IR according to Matthews et al.[16] and analysed their proportion in each grade of NAFLD. Proportion of subjects with severe IR progressively increased through the grades of NAFLD as illustrated in [Table 3]. Singh et al. showed IR in 60% of the subjects and he too demonstrated rising IR from 61.8% to 100% in Grades 1–3.[26]

There are some limitations in our study. The diagnosis of fatty liver was based on ultrasonography and not by liver biopsy. It is well known that liver enzymes are poor indicators of NAFLD and hence could be relied upon for diagnosis. Liver biopsy is an invasive procedure with inherent complications which limits its usage in routine clinical practice. USG is non-invasive and well accepted as diagnostic criteria for NAFLD and has been used in other major studies such as by Mohan et al. Hence, we preferred this method of diagnosis. The second limitation could be that since this is a cross-sectional study, temporal or causal relations between NAFLD and glucose intolerance cannot be established. The strength of the study is that the USG was interpreted by a single trained radiologist in a tertiary care setting. This translated into fewer errors in the grading of NAFLD in our study group. Further, all patients with glucose intolerance underwent OGTT to clearly define their glycaemic status, and this helped us to classify them correctly.


  Conclusion Top


This study has important clinical implications. Given the high proportion of pre-diabetes and diabetes in patients with NAFLD, it is mandatory to screen patients with NAFLD for hyperglycaemia. An early diagnosis of diabetes in this high-risk group of patients would provide an opportunity to direct therapy toward IR and optimal glycaemic control to create a favourable 'metabolic memory' early in the disease. That would reduce the subsequent risk of diabetes complications specifically and also perhaps liver complications such as progression to cirrhosis.[34]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012;55:2005-23.  Back to cited text no. 1
    
2.
Ratziu V, Bellentani S, Cortez-Pinto H, Day C, Marchesini G. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol 2010;53:372-84.  Back to cited text no. 2
    
3.
Madan K, Batra Y, Panda SK, Dattagupta S, Hazari S, Jha JK, et al. Role of polymerase chain reaction and liver biopsy in the evaluation of patients with asymptomatic transaminitis: Implications in diagnostic approach. J Gastroenterol Hepatol 2004;19:1291-9.  Back to cited text no. 3
    
4.
Agarwal SR, Malhotra V, Sakhuja P, Sarin SK. Clinical, biochemical and histological profile of nonalcoholic steatohepatitis. Indian J Gastroenterol 2001;20:183-6.  Back to cited text no. 4
[PUBMED]    
5.
Duseja A, Chawla Y. Nonalcoholic fatty liver disease in India – How much? How soon? Trop Gastroenterol 2005;26:1-3.  Back to cited text no. 5
    
6.
Mohan V, Farooq S, Deepa M, Ravikumar R, Pitchumoni CS. Prevalence of non-alcoholic fatty liver disease in urban South Indians in relation to different grades of glucose intolerance and metabolic syndrome. Diabetes Res Clin Pract 2009;84:84-91.  Back to cited text no. 6
    
7.
Hamaguchi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med 2005;143:722-8.  Back to cited text no. 7
    
8.
Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis. Ann Intern Med 1997;126:137-45.  Back to cited text no. 8
    
9.
Das K, Das K, Mukherjee PS, Ghosh A, Ghosh S, Mridha AR, et al. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology 2010;51:1593-602.  Back to cited text no. 9
    
10.
Prashanth M, Ganesh HK, Vima MV, John M, Bandgar T, Joshi SR, et al. Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. J Assoc Physicians India 2009;57:205-10.  Back to cited text no. 10
    
11.
WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157-63.  Back to cited text no. 11
    
12.
Alberti KG, Zimmet P, Shaw J, IDF Epidemiology Task Force Consensus Group. The metabolic syndrome – A new worldwide definition. Lancet 2005;366:1059-62.  Back to cited text no. 12
    
13.
American Diabetes Association. Classification and diagnosis of diabetes. Diabetes care. 2015 Jan 1;38(Supplement 1):S8-16.  Back to cited text no. 13
    
14.
World Health Organization, Western Pacific Region, The Asia Pacific Perspective. Redefining Obesity and its Treatment, World Health Organization, International Associaton for the Study of Obesity and International Obesity Task Force. Melbourne: International Diabetes Institute; 2000.  Back to cited text no. 14
    
15.
Joseph AE, Saverymuttu SH, al-Sam S, Cook MG, Maxwell JD. Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease. Clin Radiol 1991;43:26-31.  Back to cited text no. 15
    
16.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC, et al. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-9.  Back to cited text no. 16
    
17.
Mahaling DU, Basavaraj MM, Bika AJ. Comparison of lipid profile in different grades of non-alcoholic fatty liver disease diagnosed on ultrasound. Asian Pac Trop Biomed 2013;3:907-12.  Back to cited text no. 17
    
18.
Chen ZW, Chen LY, Dai HL, Chen JH, Fang LZ. Relationship between alanine aminotransferase levels and metabolic syndrome in nonalcoholic fatty liver disease. J Zhejiang Univ Sci B 2008;9:616-22.  Back to cited text no. 18
    
19.
Kallwitz ER, Kumar M, Aggarwal R, Berger R, Layden-Almer J, Gupta N, et al. Ethnicity and nonalcoholic fatty liver disease in an obesity clinic: The impact of triglycerides. Dig Dis Sci 2008;53:1358-63.  Back to cited text no. 19
    
20.
Papatheodoridis GV, Goulis J, Christodoulou D, Manolakopoulos S, Raptopoulou M, Andrioti E, et al. High prevalence of elevated liver enzymes in blood donors: Associations with male gender and central adiposity. Eur J Gastroenterol Hepatol 2007;19:281-7.  Back to cited text no. 20
    
21.
Mohammadi A, Bazazi A, Maleki-Miyandoab T, Ghasemi-Rad M. Evaluation of relationship between grading of fatty liver and severity of atherosclerotic finding. Int J Clin Exp Med 2012;5:251-6.  Back to cited text no. 21
    
22.
Kwon YM, Oh SW, Hwang SS, Lee C, Kwon H, Chung GE, et al. Association of nonalcoholic fatty liver disease with components of metabolic syndrome according to body mass index in Korean adults. Am J Gastroenterol 2012;107:1852-8.  Back to cited text no. 22
    
23.
Abangah G, Yousefi A, Asadollahi R, Veisani Y, Rahimifar P, Alizadeh S, et al. Correlation of body mass index and serum parameters with ultrasonographic grade of fatty change in non-alcoholic fatty liver disease. Iran Red Crescent Med J 2014;16:e12669.  Back to cited text no. 23
    
24.
Leite NC, Salles GF, Araujo AL, Villela-Nogueira CA, Cardoso CR. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int 2009;29:113-9.  Back to cited text no. 24
    
25.
Ortiz-Lopez C, Lomonaco R, Orsak B, Finch J, Chang Z, Kochunov VG, et al. Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD). Diabetes Care 2012;35:873-8.  Back to cited text no. 25
    
26.
Singh SP, Singh A, Pati GK, Misra B, Misra D, Kar SK, et al. A study of prevalence of diabetes and prediabetes in patients of non-alcoholic fatty liver disease and the impact of diabetes on liver histology in coastal Eastern India. J Diabetes Mellit 2014;4:290-6.  Back to cited text no. 26
    
27.
Haukeland JW, Konopski Z, Linnestad P, Azimy S, Marit Løberg E, Haaland T, et al. Abnormal glucose tolerance is a predictor of steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease. Scand J Gastroenterol 2005;40:1469-77.  Back to cited text no. 27
    
28.
Yun JW, Cho YK, Park JH, Kim HJ, Park DI, Sohn CI, et al. Abnormal glucose tolerance in young male patients with nonalcoholic fatty liver disease. Liver Int 2009;29:525-9.  Back to cited text no. 28
    
29.
Faerch K, Borch-Johnsen K, Holst JJ, Vaag A. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: Does it matter for prevention and treatment of type 2 diabetes? Diabetologia 2009;52:1714-23.  Back to cited text no. 29
    
30.
Deepa R, Sandeep S, Mohan V. Abdominal obesity, visceral fat and Type 2 diabetes – Asian Indian Phenotype. In: Mohan V, Rao Gundu HR, editors. Type 2 Diabetes in South Asians: Epidemiology, Risk Factors and Prevention. Under the Aegis of SASAT, Jaypee Brothers Medical Publishers; 2006. p. 138-52.  Back to cited text no. 30
    
31.
Park SH, Jeon WK, Kim SH, Kim HJ, Park DI, Cho YK, et al. Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults. J Gastroenterol Hepatol 2006;21:138-43.  Back to cited text no. 31
    
32.
Bajaj S, Nigam P, Luthra A, Pandey RM, Kondal D, Bhatt SP, et al. A case-control study on insulin resistance, metabolic co-variates and prediction score in non-alcoholic fatty liver disease. Indian J Med Res 2009;129:285-92.  Back to cited text no. 32
[PUBMED]  [Full text]  
33.
Bhat G, Baba CS, Pandey A, Kumari N, Choudhuri G. Insulin resistance and metabolic syndrome in nonobese Indian patients with non-alcoholic fatty liver disease. Trop Gastroenterol 2013;34:18-24.  Back to cited text no. 33
    
34.
Pirola L, Balcerczyk A, Okabe J, El-Osta A. Epigenetic phenomena linked to diabetic complications. Nat Rev Endocrinol 2010;6:665-75.  Back to cited text no. 34
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Methodology
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed370    
    Printed29    
    Emailed0    
    PDF Downloaded99    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]