Prevalence of non-alcoholic fatty liver disease among diabetes, prediabetes and healthy population

ABSTRACT

Introduction:

Non-alcoholic fatty liver disease (NAFLD) is a global emerging health issue, which is due to extra fat deposition in the liver that poses a serious risk of liver cirrhosis. Our study assessed the glycaemic status and NAFLD in health patients coming for a regular health check-ups.

Material and Methods:

This descriptive study was done on 192 healthy populations aged 30–70 years who underwent general health check-ups. History, clinical examination, heamtological and radiological workup were done and data were statistically evaluated.

Results:

The age of the study population was between 30 and 70 years with an average age of 50 years and the study sample size was 190. Prevalence of prediabetes was 35.93%, diabetes at 17.18% and euglycaemics were 45.83% in our study group. Among diabetics and prediabetics, 30% and 31% were having raised transaminase. Among euglycaemics, around 19% had raised transaminase. On ultrasound scans among the diabetic group, the prevalence of fatty liver was 57.6% whereas in the prediabetic group it was 46.4%. Among the normal euglycaemic group, 22.7% had fatty liver.

Conclusion:

NAFLD is multifactorial and associated with diabetes and can progress to cirrhosis of the liver if untreated. There is a need to have more focus on screening, awareness, nutritional counselling and treatment at the primary care level.

Introduction

Non-alcoholic fatty liver disease (NAFLD) burden has grown over the past years and has been recognised as one of the major health burdens. It is due to the accumulation of excess fat in form of triglycerides in the liver. Some patients may develop liver cell inflammation manifested as raised liver enzymes known as non-alcoholic steatohepatitis (NASH). A major concern with NASH is due to the risk of progression to cirrhosis of the liver, hepatocellular carcinoma and liver failure. As it can be prevented, it is imperative to diagnose this condition in general health check-ups.

NAFLD is becoming the most common liver disorder worldwide with a median prevalence of around 20% in the general population[1] and 42–70% in type 2 diabetes mellitus (T2DM).[2]

Many studies have shown a high prevalence of NAFLD among the diabetic population compared to the healthy population. There is an epidemic of T2DM in India and there has been a significant increase in prediabetes and T2DM patients in recent years and is expected to rise to 439 million by 2030.[3]

The rising prevalence of prediabetes is also a concern and an opportunity to achieve better glycaemic control. Indian Council of Medical Research–India Diabetes (ICMR-INDIAB) study revealed a higher prevalence of prediabetes at 10.3% compared to the 7.3% prevalence of diabetes mellitus.[4]

Fat in the liver has been much talked about from earlier times. In 1910, a landmark paper was published that demonstrate abnormal amount of fat distribution in the liver, in autopsy series.

NAFLD is an emerging public health burden in India and also worldwide. NAFLD consists of two distinct diseases, i.e., non-alcoholic fatty liver (NAFL) and NASH. NAFL is defined as hepatic steatosis with an absence of inflammation (both on imaging and histology) in a subject without significant alcohol consumption and in whom there are no other causes of secondary steatosis.

Prevalence of NAFLD has been well documented to be higher in diabetes mellitus and obesity but among prediabetes, there are only a few studies done. We did a cross-sectional study on general health check-up participants to assess their glycaemic status and evidence of fatty liver at the tertiary care centre in New Delhi and Patna.

Material and Methods

Study participants

This descriptive study was done on 190 healthy populations aged 30–70 years who underwent general health check-ups between July 2017 and November 2020 at a tertiary care centre in Delhi and Patna.

Sampling methods

Patients who gave a history of pre-existing diabetes, on Ayurveda medications, past history of viral hepatitis, known dyslipedaemics, unknown drugs, use of alcohol or having significant comorbidities like sepsis, organ failure and malignancy were excluded from this study.

Detailed medical history and clinical examination details were included. Physical examination details like height, weight and waist circumference were recorded. The haematological and biochemical investigation included fasting and postprandial blood sugar, fasting lipid profile, liver function test, glycosylated haemoglobin (HbA1c), human immunodeficiency virus (HIV), hepatitis B and C serology and ultrasound abdomen that were recorded as part of general health check-up.

After aseptic precautions, venous blood was collected in ethylene diamine tetra acetic acid and plain vacutainer after a minimum 8 h of fasting. Complete blood sugar profile, liver function tests and ultrasound of the whole abdomen was done in all patients.

Prediabetes state was defined where HbA1C was between 5.7 and 6.5%[5] and diabetic where HbA1C was equal to or more than 6.5%. Elevated liver enzymes alanine transaminase (ALT)/aspartate transaminase (AST) were considered when levels were more than 1.5 times the normal.

Ultrasound abdomen was used to categorise fatty liver. These included if liver echogenicity exceeds that of renal cortex and spleen and there was attenuation of the ultrasound wave, loss of definition of the diaphragm and poor delineation of the intrahepatic architecture.[6]

Statistical analysis

Analysis was performed using IBM SPSS 22.0 (SPSS, Inc., Chicago IL). The mean, standard deviation (SD) and range of the two measurements were calculated for the different parameters. To compare differences between saccades within the two measurements, the paired sample t-test was used, after checking the normality of the distribution visually. A probability level of alpha <0.05 was considered as significant.

All procedures followed were in accordance with the ethical standards of the responsible committee.

Results

The age of the study population was between 30 and 70 years with an average age of 50 years. Our study sample size was 190. Based on HbA1c, study participants were categorised into diabetic, prediabetes and glycaemic groups.

Prevalence of prediabetes was 36.32%, diabetes at 17.36% and euglycaemics were 46.32% in our study group [Table 1].

Table 1.

Classification based on study population (n=190)

Euglycaemic	88 (46.32%)
Prediabetic	69 (36.32%)
Diabetic	33 (17.36%)

Among those found to have diabetes, 30% were having raised transaminase whereas in prediabetic it was found to be 31%. Among euglycaemics, around 19% had raised transaminase [Table 2].

Table 2.

Elevated transaminase levels with blood sugar

Blood sugar	Raised Transaminase
Diabetic	30%
Prediabetic	31%
Normal blood sugar	19%

Ultrasound findings revealed the prevalence of fatty liver among 37.37% of the total study population [Table 3]. Among the diabetic group, the prevalence of fatty liver was 57.6% whereas in the prediabetic group it was 46.4%. Among the normal euglycaemic group, 22.7% had fatty liver. Chi-square test showed significant difference (p = 0.022).

Table 3.

Ultrasound findings of fatty liver

	Diabetes (n=33)	Prediabetes (n=69)	Euglycaemics (n=88)
Raised ALT	8	17	15
Raised AST	8	13	8
Normal liver enzymes	17	39	65
Fatty liver	19	32	20

Discussion

NASH is defined histologically as steatosis, inflammation with the presence of at least one of the three histological features (ballooning of hepatocytes, Mallory’s hyaline, fibrosis on liver histology).[7]

The definition of NASH also excludes hepatitis B and C and conditions like total parental nutrition, various inborn errors of metabolism and surgical procedures.[8]

The majority of patients with fatty liver are asymptomatic (48–100%); however, few may have symptoms of fatigue, right upper abdomen pain, occasional neurological deficit, obstructive sleep apnoea or polycystic ovarian syndrome. Acanthosis nigricans can be the only sign in addition to hepatomegaly.

There are many risk factors for diabetes in India. These include age, male sex, family history, urban residence, income status, hypertension and abdominal obesity. Abdominal obesity is also linked to fatty liver and liver dysfunction.

The relationship between insulin resistance and NAFLD becomes more complex with the term ‘hepatogenous diabetes’. It is a known fact that there is an increased prevalence of diabetes in cirrhosis of various aetiology. Insulin resistance is very common in NAFLD and hepatic steatosis usually precedes the development of diabetes. The factors on which the development of diabetes depends are susceptible person, obesity and ethnicity. In general, 75% of diabetes mellitus type 2 have fatty infiltration.[9]

The gold standard for diagnosis of NAFLD remains histopathology in light of chemical clinical history. It is an invasive process and macrovesicle steatosis occupying at least 5% of hepatocytes is the best way to diagnose fatty liver by histology. However, there are many flows like sampling error, small liver biopsy and variability of steatosis location in the liver.

In 2012, NAFLD guidelines published in the hepatology journal provided evidence of steatosis ‘either by imaging or histology’ thereby providing another non-invasive test to diagnose fatty liver without biopsy. Various imaging modalities have been used to define NASH like ultrasound, computerised tomography (CT) scan, magnetic resonance imaging (MRI) or Transient elastography (FibroScan).

Since it is not a practise to do a liver biopsy on this widely prevalent condition, Fibroscan (elastography) has been used as an upcoming tool to differentiate between simple steatosis and NASH. With such a high prevalence of fatty liver in diabetes, it is important to consider the use of transient elastography in the wellness clinic.

Currently, ultrasound is the most commonly used modality to evaluate hepatic steatosis as the cost is low, its easy availability and safety.

Ultrasound is a non-invasive way to diagnose fatty liver. Although ultrasound is operator-dependent but bright liver hepatic echogenicity and measurement of the difference between liver and kidney in echo amplitude, help to diagnose fatty liver. Ultrasound can also be used to grade fatty liver. There is inter and intraobserver variation and also this grading does not correlate to histology.[6] In a study, it was found that ultrasound as a screening modality is as sensitive as a CT scan for the diagnosis of fatty liver.[10]

Various other parameters like the ratio of AST/ALT help to predict the severity of NASH. NASH-related liver cirrhosis and hepatocellular carcinoma are now distinct identities. Liver enzymes are a cost-effective test to diagnose liver dysfunction.

Many laboratory abnormalities have been associated with NAFL. The most obvious is elevated AST/ALT and in one study, the average level of 55 and 74 U/L have been recorded. The ratio of AST: ALT < 1 suggests mild disease whereas >1 indicates fibrosis. The other findings are elevated gamma glutamyl transferase, hyperuricaemia, positive antinuclear antibody (ANA) (~30%) and elevated iron indices (in 20–60%) patients.[11]

In our study, patients with diabetes having raised transaminases are 30%, while prediabetics have 31% and non-diabetics have 19%. Patients having raised transaminases (AST/ALT) along with abnormal ultrasound are 44%.

Various studies in India have shown the prevalence of NASH to vary from 9% to 35%. There is a difference in rural/urban prevalence reported in one study from Bengal, with an expected more prevalence in urban settings.[7]

The prevalence is more in diabetics and obese patients. The prevalence of fatty liver on ultrasound also varies from 50% to 75% in diabetes mellitus type 2.[12]

Weight loss agents (orlistat, sibutramine, Rimonabant) have shown good results on liver fat and are usually not recommended. Bariatric surgery (gastric banding, gastric bypass) improves the weight, insulin resistance and liver histology in NASH. These surgeries are indicated when the conventional approach to weight reduction fails and patients have morbid obesity. Monotherapy with ursodeoxycholic acid (UDCA) has not been shown to benefit liver histology in randomised control trial (RCT). This is compared to a combination of UDCA with vitamin E (800 IU/day) over 2 years. Among the oral hypoglycaemic agents, both metformin and pioglitazones have shown improvement in transaminase and also hepatic steatosis.

As both prediabetic state and fatty liver can progress and increase mortality, both pharmacological and non-pharmacological (diet, exercise, weight loss) interventions to prevent complications must be suggested at the time of first diagnosis/health check-up.

Limitations

Several epidemiological studies use a presumptive diagnosis of NAFLD/NASH based on abnormal transaminase, with blood test negative for viral studies and echogenic or bright liver on ultrasound consistent with fatty infiltration. As there is no histological correlation, this is a major drawback of our study.

Conclusion

NAFLD is a rapidly evolving public health problem, which needs urgent attention. Awareness regarding the importance of lifestyle modification, risk factors and symptoms may help in its early diagnosis. Access to the family doctor and strengthening primary health care would help in prevention, early diagnosis and treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.