Comparison of the severity of non-alcoholic fatty liver disease in diabetic and non-diabetic obese patients

Introduction: Nonalcoholic fatty liver disease presents a broad spectrum of histopathological alterations, from steatosis to liver cirrhosis. Patients with diabetes mellitus (DM) present increased incidence and severity of NAFLD. Objective: Determine the prevalence and severity of NAFLD in diabetic and non-diabetic obese patients undergoing bariatric surgery. Method: The evaluation of liver biopsies was carried out through NAFLD activity score (NAS) in order to evaluate degree of hepatic steatosis, presence of ballooning, inflammatory activity and degree of fibrosis. Results: A total of 154 patients who have undergone bariatric surgery with intraoperative biopsy were observed and divided into two BMI ranges: from 35 to 44.9 and from 45 to 54.9. 32 (20.8%) from 154 patients were diabetic and 122 (79.2%) were nondiabetic. Patients with DM were significantly older than patients without the disease, presenting 41.29 ± 9.40 years vs 36.71 ± 10.13 years in the group with BMI of 35 to 44.9 (p=0.049); and 45.13 ± 7.10 years vs 37.00 ± 9.24 years in the group with BMI of 45 to 54.9 (p=0.024). In the histological evaluation, patients with DM from the BMI group of 35 to 44.9 had a strong association with higher prevalence and severity of steatosis, balloning, inflammation, fibrosis and steatohepatitis. Conclusion: The present study confirms the high prevalence of NAFLD in patients with Morbid Obesity. Prevalence and severity increase proportionally to BMI and who have DM as comorbidity.

triglycerides in hepatocytes 6 . This accumulation of lipid is associated with increased gluconeogenesis, decreased glycogen synthesis, which exacerbates IR and increases low-grade inflammation, leading to the progression of liver disease to fibrosis, cirrhosis, and increased risk of hepatocarcinoma 7 .
Weight loss is the most important factor in controlling NAFLD. The weight loss goal, when starting a diet with a caloric reduction of about 25%, is approximately 10%, although the need for weight loss varies according to the severity of the disease.
The effects of bariatric surgery on NAFLD are related to improved histology, including resolution of NASH in 75% of cases, reduction of fibrosis in 35% of cases 8 , and partial reversion of cirrhosis 9 , effects achieved with no other treatment, including diet and habits changing.
In 2015, the International Diabetes Federation published data estimating the prevalence of type 2 diabetes (T2DM) in 415 million people and with a prospect of growth to 642 million by the year 2040 10 .
Adequate glycemic control of T2DM is crucial in preventing complications, improving quality of life and reducing mortality 11 . However, even with new advances in clinical treatment, drug control is successful in less than 30% of patients 12,13 . In this context, bariatric surgery and metabolic surgery emerge as forms of control that go beyond weight loss, further improving metabolic control, with a consequent reduction in cardiovascular risk 14

PATIENTS AND METHODS
In this retrospective study, 228 obese, diabetic and non-diabetic patients who underwent bariatric surgery by the same team from the Irmandade Santa Casa de Misericórdia of Porto Alegre (ISCMPA), from 2016 to 2018, underwent perioperative liver biopsy.
We excluded 74 patients due to reported alcohol consumption greater than 140 g/week for men and 70 g/week for women 16 , use of drugs or hepatotoxic medications, presence of other liver diseases, previous weight reduction procedures -previous bariatric surgery or intra-gastric balloon insertion. We assessed the remaining 154 patients using anthropometric data, body mass index (BMI), laboratory variables and histopathological variables. We considered patients with T2DM those already in treatment with insulin and oral antidiabetics in the preoperative evaluation, and those without treatment but with fasting glucose greater than 126 mg/dL and with glycosylated hemoglobin (HbA1c) >6.5 in consecutive analyzes 17 . We considered hypertensive patients those in antihypertensive use or with blood pressure >130/85mmHg 18 . We divided the patients into two groups according to a BMI cutoff of 45kg/m 2 and, subsequently, between diabetics and non-diabetics, to try to quantify the effects of obesity according to its evolution and the association with  Kleiner 20 and collaborators, to assess the degree of HS, the presence of ballooning, inflammation activity and the degree of fibrosis.
We classified the degree of fibrosis as: stage 0, without fibrosis; grade 1a, when mild fibrosis was identified in zone 3; grade 1b, when moderate fibrosis was identified in zone 3; grade 1c, when only periportal/ portal fibrosis was identified; grade 2, when periportal/ portal fibrosis and zone 3 were identified; grade 3, when bridging fibrosis was identified; and grade 4, when cirrhosis was identified.

STATISTICAL ANALYSIS
In the descriptive analyzes, were expressed quantitative variables as mean ± standard deviation (SD) and median, and the qualitative variables, as frequency

RESULTS
The average hospital stay was 4.3 days for the entire group. There was no report of any surgical We categorized the laboratory variables Ott-Fontes Comparison of the severity of non-alcoholic fatty liver disease in diabetic and non-diabetic obese patients as normal or altered. According to the definition of metabolic syndrome, we considered, as altered values, total cholesterol (TC) >200 mg/dL, triglycerides (TG) ≥150 mg/dL, and HDL cholesterol <40 mg/dL for men and <50 mg/dL for women. Patients with T2DM are more prone to alterations in such laboratory tests, although this association has not been statistically significant. Table 2 shows the data collected in the laboratory tests.
The histological evaluation, shown in Table   3, indicates that patients with T2DM in the group with a BMI 35-44.9 kg/m 2 had increased prevalence and severity of HS, ballooning, inflammation, fibrosis and NASH.     Ott-Fontes Comparison of the severity of non-alcoholic fatty liver disease in diabetic and non-diabetic obese patients diabetic patients may be prone to develop diabetes and hypertension, as a pathophysiological sequence of the metabolic syndrome 27 .
Patients with T2DM are more prone to display alterations in laboratory markers for MS. Although this association has not been statistically significant, it is consistent with the literature.
NAFLD encompasses a wide spectrum of injuries, such as steatosis, steatohepatitis and fibrosis, and often one finds these three pathologies in the same patient. In the presence of fibrosis, progression to cirrhosis occurs in 20% of cases. Cirrhotic patients, on their turn, display 10% progression to hepatocarcinoma 28