|Year : 2017 | Volume
| Issue : 1 | Page : 8-11
Prevalence of nonalcoholic fatty liver disease in type 2 diabetes mellitus and its relation with insulin resistance in South Gujarat Region
Krishnakant Niranjan Bhatt, Vaidya Pranav, Yadav Dipika, Nama Dharmesh, Nittala Radhika, Sharma Arvind
Department of Medicine, Government Medical College, New Civil Hospital, Surat, Gujarat, India
|Date of Web Publication||14-Mar-2017|
Krishnakant Niranjan Bhatt
E-2/4, Prof. Bungalows, New Civil Hospital Campus, Surat, Gujarat
Source of Support: None, Conflict of Interest: None
Background: Nonalcoholic fatty liver disease (NAFLD) is commonly associated with type 2 diabetes mellitus (DM) though its prevalence is not well studied. We conducted a prospective study of prevalence of NAFLD in patients with type 2 DM and its relation with Insulin Resistance. Materials and Methods: 100 patients of Type 2DM attending Tertiary care center in South Gujarat were evaluated. Abdominal ultrasonography was performed to determine the presence of fatty liver. For assessment of Insulin Resistance, Homeostasis Model Assistant - Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated. A probability value of P < 0.05 was considered statistically significant. Results: The study group (n = 100) was divided into a NAFLD group (n = 45) and a non-NAFLD group (n = 55). The prevalence of NAFLD was 45%. The NAFLD subgroup had higher prevalence of obesity (measured by BMI), central obesity (measured by waist circumference and waist hip ratio), higher HbA1c, higher triglyceride levels. HOMA-IR and QUICKI indexes for Insulin Resistance were significantly higher in NAFLD group than Non NAFLD group (P value 0.03, 0.04). Conclusion: The prevalence of NAFLD is high in patients of Type 2 DM. Insulin resistance seems to be correlated with the presence of NAFLD among T2DM patients.
Keywords: Insulin Resistance, nonalcoholic fatty liver disease, type 2 diabetes mellitus
|How to cite this article:|
Bhatt KN, Pranav V, Dipika Y, Dharmesh N, Radhika N, Arvind S. Prevalence of nonalcoholic fatty liver disease in type 2 diabetes mellitus and its relation with insulin resistance in South Gujarat Region. J Mahatma Gandhi Inst Med Sci 2017;22:8-11
|How to cite this URL:|
Bhatt KN, Pranav V, Dipika Y, Dharmesh N, Radhika N, Arvind S. Prevalence of nonalcoholic fatty liver disease in type 2 diabetes mellitus and its relation with insulin resistance in South Gujarat Region. J Mahatma Gandhi Inst Med Sci [serial online] 2017 [cited 2017 Aug 16];22:8-11. Available from: http://www.jmgims.co.in/text.asp?2017/22/1/8/202001
| Introduction|| |
Nonalcoholic fatty liver disease (NAFLD) denotes a spectrum of conditions occurring in those who do not consume alcohol in amounts, generally considered to be harmful to the liver and characterized histologically by macrovesicular hepatic steatosis. NAFLD is the hepatic pandemic of the twenty- first century, being the leading cause of chronic hepatic disease in the world. It is emerging as the most common chronic liver disease in both Western countries and also in other parts of the world.,
NAFLD is a disease of our generation which has exploded onto the clinical landscape over the past 25 years. The problem of NAFLD is not confined to its potential to cause serious liver-related morbidity and mortality. It frequently occurs with features of the metabolic syndrome including obesity, type 2 diabetes mellitus., Dyslipidemia  and hypertension  Not surprisingly, 10–75% of NAFLD patients have T2DM and 21–72% of patients with diabetes are reported to have NAFLD.
NAFLD has been associated very closely with the presence of type 2 diabetes mellitus. DM is an important determinant of both presence and severity of NAFLD. Insulin resistance plays a central role in the pathogenesis of NAFLD although the initial site and cause of insulin resistance is unknown. The two key pathophysiologic abnormalities associated with insulin resistance that play a role in the genesis of a fatty liver are hyperinsulinemia and increased free fatty acid delivery to the liver.
The mortality rate of diabetic patients due to cirrhosis is more than twice the general population and patients with both NAFLD and DM have a poorer prognosis in terms of higher rates of cirrhosis and mortality. Available literature on NAFLD and its relation to coronary artery disease in diabetes patients from India is sparse. This may be related to the presumption that the condition is benign and has a nonprogressive course. In addition, a large burden of viral hepatitis in India tends to reduce the priority accorded to this condition. Hence, the present study was planned to study the prevalence of NAFLD in type 2 Diabetes mellitus patients in south Gujarat and its correlation with Insulin Resistance.
| Materials and Methods|| |
The present study was carried out at Medicine Department, New Civil Hospital and Government Medical College, Surat from January 2012 to October 2013. An initial screening in the form of detailed history taking and clinical examination was carried out to include/exclude the patients in the study. A total 100 patients with age more than 18 years were included who were having diabetes of minimum 1-year duration. Exclusion criteria included: patients who consumed more than 40 g alcohol per week, patients who were found to have other liver diseases such as malignancies, hepatitis, liver abscesses, and patients having derangement of hepatic functions due to any other febrile illnesses/disease. The study was approved by the ethical committee.
A detailed history regarding the disease was taken, and complete physical examination was performed. BMI was calculated as a measure of obesity, whereas waist/hip ratio was measured as an index of splanchnic fat accumulation.,
After an overnight fast, serum samples were obtained from all subjects for liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and alkaline phosphates), serum lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]), fasting blood glucose (FBS), HBA1C, and fasting insulin levels. Homeostasis Model Assistant–Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity check Index (QUICKI) were calculated as measures of insulin resistance and sensitivity using following formula:
HOMA-IR= [fasting insulin (μU/ml) ×fasting glucose (mmol/l)]/22.5
QUICKI = 1/[log (fasting insulin (μU/ml)) ± log (glucose (mg/dl))]
All subjects underwent abdominal ultrasonography by the same radiologist as a routine investigation as other patients who attend hospital for evidence of fatty liver disease. Based on ultrasonography findings (diffuse increase in echogenicity as compared to that of the spleen or renal cortex), patients were categorized as those with NALFD and those without NALFD.
A detailed comparison was made between the prevalence of fatty liver in type 2 diabetics by the above four methods. Descriptive statistics were performed on all study parameters (mean, standard deviation and range). Statistical analysis was carried out for study parameters between the two groups (NAFLD and non-NAFLD) using student's t-test. P < 0.05 was considered significant.
| Results|| |
A total 100 patients with T2DM were enrolled during the study period. The mean age of the patient was 55.07 years. Out of 100 patients, 49 were males and 51 were females. None of the subjects had histories of alcohol consumption. Of 100 patients with T2DM, 45 (45%) were found to have changes of fatty liver disease in abdominal ultrasonography examination. Prevalence of fatty liver disease was almost same in males and females (22 males and 23 females). Elevated ALT (>40 IU/dl) was seen in 7 patients while 3 patients had AST >40 IU/dl. A large proportion of the study population was obese as mean BMI was 27.12 (17.2–37.05). [Table 1] demonstrates baseline clinical and biomedical parameters of the study population. Both NAFLD and non-NAFLD groups were compared in regard to demographic, anthropometric, and biomedical characteristics. BMI, waist/hip ratio, S. triglyceride level were significantly high [Table 2] in NAFLD group as compared to non-NAFLD group (P = 0.009,0.0001,0.003, respectively). Quantitative measures of insulin resistance S. fasting insulin, HOMA-IR score, and QUICKI score showed significant association of NAFLD with increased insulin resistance. None of the other parameters differed significantly between the two groups.
|Table 1: Demographic, anthropometric, and biomedical characteristics of 100 patients with type 2 DM|
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|Table 2: Comparison of parameters between NAFLD and Non-NAFLD diabetic patients|
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| Discussion|| |
In the present study, the prevalence of NAFLD in 100 patients of Type 2 diabetes mellitus was 45% based on abdominal ultrasound examination. This is similar to other studies that have reported the prevalence of NAFLD among DM patients at approximately 50% (range: 21–78%). There were no significant differences in sex distribution between the two groups. This is in contrast to previous studies where the prevalence of NAFLD among men and women were found to be varied. Whereas in some, NAFLD was considered to be more common among women,, in others it was reported to be more prevalent among men., In recent studies, as in ours, it has been suggested that both sexes might be afflicted equally.
We found that glycemic control both in terms of fasting glucose as well as HBA1C in patients with NAFLD were statistically not significant as compared to non-NAFLD.(P = 0.07 and 0.24, respectively). This observation suggests a noncausal relationship between glycemic control and fatty liver.
BMI was significantly higher in patients with NAFLD (28.27 ± 3.77) than those without NAFLD (26.19 ± 4.02 P = 0.009). Obesity is the most common entity associated with NAFLD that has been reported in various other studies.
In our study, the waist/hip ratio was significantly different between the two groups (P = 0.0001). Waist/hip ratio denotes abdominal fat distribution. Kral et al. observed significant correlation between waist/hip ratio and the degree of hepatic steatosis, even in patients with normal BMI. Visceral fat and fatty liver represent special depots of adiposity-related to the pathogenesis of Insulin Resistance and may be part of an overall axis of central adiposity. Organ-specific deposition of fat is a strong predictor of hyperinsulinemia and/or insulin resistance. Analogous to fat in the liver, increased intra-myocellular triglyceride content as accessed via muscle biopsy  or magnetic resonance imaging/computed tomography, closely correlates with muscle IR. The sequence of events leading to ectopic accumulation of triglycerides has been referred to as the overflow hypothesis, according to which IR is the result of the inability of the adipose organ to expand to accommodate excess calories. Once the capacity of the fat cell to store triglycerides is exceeded, fat overflows to other tissues (muscle and liver), where the intracellular triglyceride metabolism interferes with insulin signaling, glucose transport/phosphorylation, and glycogen synthesis in muscle and augments hepatic gluconeogenesis.
In the present study, we observed that patients in the NAFLD group had a higher prevalence of Insulin resistance as measured by S. fasting insulin, HOMA-IR, and QUICKI; as compared to non-NAFLD group (P − 0.03 and 0.04, respectively). In insulin-resistant states, hyperinsulinemia may induce membrane-bound transcription factor SREBP-1c, which activates most genes involved in lipogenesis. Hyperinsulinemia per SE may trigger hepatic fat deposition, as empirically demonstrated by the hepatic steatosis occurring under the capsule of livers in patients undergoing peritoneal dialysis, where insulin is routinely added to the dialysate. These observations suggest a primary role of dysfunctional lipid metabolism in the onset and persistence of NAFLD, as part of a more generalized event referred to as lipotoxicity, leading to ectopic lipid accumulation. Perhaps the strongest evidence supporting the importance of IR in the pathophysiology of NAFLD are then ascent data provided by recent clinical strategies that have been designed to improve insulin sensitivity in the liver ,,, (Metfromin) and the periphery  (Thiazolidinediones) in patients with NAFLD.
We observed mean cholesterol, HDL, and LDL levels did not defer significantly between the two groups. Only the mean triglyceride levels showed significant correlation with the presence of NAFLD (P = 0.03). Dyslipidemia are commonly associated with NAFLD. Previous Studies have shown that 20–92% of patients diagnosed with NAFLD have hyperlipidemia, including hypertriglyceridemia, hypercholesterolemia or both. In one study, almost 50% of the patients diagnosed with hyperlipidemia had NAFLD on ultrasound evaluations but only hypertriglyceridemia and not hypercholesterolemia was shown to pose a risk of developing liver fatty disease. Hypertriglyceridemia along with diabetes and obesity increases the risk of NAFLD development.
We found that transaminase levels were not statistically significant between the NAFLD and non-NAFLD groups (P = 0.06 and 0.05 for AST and ALT, respectively). Previous studies have shown that mild to moderate elevations of serum aminotransferase are common in NAFLD, and normal values can be found in up to 78% of patients at any time, even when complete histological findings are present. Suggesting a poor correlation between transaminase levels and disease severity.
The clinical spectrum of NAFLD warrants continued research to determine its pathogenesis and to improve diagnostic modalities. It is hoped that improved imaging techniques and the discovery of serum biomarkers, as well as the development of clinical algorithms, will enable a more accurate diagnosis of NASH without the need for a liver biopsy. A multimodal treatment plan that targets obesity, insulin resistance, hyperlipidemia, and hypertension might be the best option.
A limitation of this study is that the diagnosis of NAFLD was based on ultrasonography and exclusion of known etiologic factors of chronic liver disease, but it was not confirmed by liver biopsy. It is known that none of the radiological features can distinguish between steatohepatitis and other types of NAFLD and that only liver biopsy can assess the severity of damage and the prognosis., However, liver biopsy is not easily applied in large epidemiological studies. Conversely, ultrasonography is by far the most common method of diagnosing NAFLD in clinical practice and has a very good sensitivity and specificity in detecting moderate and severe steatosis in patients with the biopsy-proven disease.,, Indeed, it has been reported that the presence of >33% fat on liver biopsy is optimal for ultrasound detection of steatosis, although ultrasonography is not completely sensitive, particularly when hepatic fat infiltration is <33%.
| Conclusion|| |
The present study revealed a high incidence of NAFLD in Type 2 diabetes patients stressing the need for early screening. Further, our findings support the hypothesis that Insulin resistance was correlated with the presence of NAFLD among diabetic patients. Future follow-up studies using larger cohorts of patients are necessary to validate these results and to extend these findings among NAFLD patients without type 2 diabetes.
Dean Dr. R. Dixit, Medical Suprintendent and Professor of Radiology Dr. M. K. Vadel, Professor of Biochemisry, Dr. S. M. Patel, Associate Professor of Community Medicine Dr. Abhay Kavishwer.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]