Effect of Empagliflozin and Pioglitazone on left ventricular function in patients with type two diabetes and nonalcoholic fatty liver disease without established cardiovascular disease: a randomized single-blind clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder that increases the risk for cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Global longitudinal strain (GLS) is an indicator of left ventricular (LV) mechanics and can detect subclinical myocardial dysfunction. We compared the effects of pioglitazone and empagliflozin on GLS in patients with T2DM and NAFLD without established atherosclerotic cardiovascular disease. METHODS: This study was a 24-week randomized, single-blind, and parallel-group (1: 1 ratio) clinical trial. Seventy-three participants with T2DM (being treated with metformin) and NAFLD but without established atherosclerotic cardiovascular disease (ASCVD) were randomized to empagliflozin or pioglitazone. Liver steatosis and fibrosis were measured using transient elastography, and GLS was measured by echocardiography. The primary endpoint was the change in GLS from baseline to week 24. Secondary end points include changes in controlled attenuation parameter (CAP) and Liver stiffness measure (LSM). RESULTS: In this study, GLS improved by 1.56 ± 2.34% (P < 0.01) in the pioglitazone group and 1.06 ± 1.83% (P < 0.01) in the empagliflozin group without a significant difference between the two groups (P = 0.31). At baseline, GLS was inversely associated with the severity of liver fibrosis: r = - 0.311, P = 0.007. LSM in the pioglitazone and empagliflozin group [(-0.73 ± 1.59) and (-1.11 ± 1.33)] kpa (P < 0.01) decreased significantly. It was without substantial difference between the two groups (P = 0.26). Empagliflozin and pioglitazone both improved controlled attenuation parameter. The improvement was more critical in the empagliflozin group: -48.22 + 35.02 dB/m vs. -25.67 + 41.50 dB/m, P = 0.01. CONCLUSION: Subclinical cardiac dysfunction is highly important in patients with T2DM and with NAFLD. Empagliflozin and Pioglitazone improve LV mechanics and fibrosis in patients without established ASCVD. This has a prognostic importance on cardiovascular outcomes in high-risk patients with T2DM. Moreover, empagliflozin ameliorates liver steatosis more effectively them pioglitazone. This study can serve as a start point hypothesis for the future. Further studies are needed to explore the concept in larger populations. TRIAL REGISTRATION: This trial was registered in the Iranian Registry of Clinical Trials (IRCT): "A Comparison between the Effect of Empagliflozin and Pioglitazone on Echocardiographic Indices in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease" IRCT20190122042450N5, 29 November 2020. https://www.irct.ir/search/result?query=IRCT20190122042450N5 .

Non-alcoholic fatty liver disease and compromised endothelial function in people with type 2 diabetes.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) frequently coexists with type 2 diabetes mellitus (T2DM) and synergistically contributes to the development of atherosclerosis. Flow-mediated dilation (FMD) is a commonly used noninvasive test for assessing endothelial function. The main objective of this study was to explore FMD in patients with T2DM with and without NAFLD. METHODS: In this cross-sectional study, conducted on people with T2DM, NAFLD was defined as controlled attenuation parameter (CAP) score > 302 dB/m. Endothelial dysfunction was detected when arterial FMD of brachial artery was equal or less than 0.7%. Regression analyses were applied to assess factors associated with impaired FMD. RESULT: A total of 147 patients (72 with NAFLD and 75 without NAFLD) were included in the final analysis. Patients with NAFLD were more likely to develop FMD ≤ 7% (77.8% vs. 58.7%, P = 0.01). In multivariate analysis, NAFLD (OR = 2.581, 95% CI (1.18-5.62), P = 0.017) and hypertension (HTN) (OR = 3.114, 95% CI (1.31-7.35), P = 0.010) were associated with an increased risk of impaired FMD. However, female sex was associated with a decreased risk of impaired FMD (OR = 0.371, 95% CI (0.15-0.87), P = 0.024). CONCLUSION: NAFLD is associated with endothelial dysfunction in people with T2DM. This risk is comparable with the risk imposed by HTN, highlighting the importance of screening and management of NAFLD in these patients.

The combination of sofosbuvir and daclatasvir is effective and safe in treating patients with hepatitis C and severe renal impairment.

BACKGROUND AND AIM: Many of the treatment regimens available for hepatitis C include sofosbuvir. Unfortunately, sofosbuvir has not been recommended for use in patients with severe renal impairment leaving these group of patients with very few options. Nevertheless, there are many reports in which these patients have been treated with sofosbuvir-containing regiments without important adverse events. This study aims at determining the safety and effectiveness of a sofosbuvir-based treatment in patients with severe renal impairment, including those on hemodialysis. METHOD: We enrolled subjects with hepatitis C and estimated glomerular filtration rate under ml/min/1.73m2 from 13 centers in Iran. Patients were treated for 12 weeks with a single daily pill containing 400-mg sofosbuvir and 60-mg daclatasvir. Patients with cirrhosis were treated for 24 weeks. Response to treatment was evaluated 12 weeks after end of treatment (sustained viral response [SVR]). ClinicalTrials.gov identifier: NCT03063879. RESULTS: A total of 103 patients were enrolled from 13 centers. Seventy-five patients were on hemodialysis. Thirty-nine had cirrhosis and eight were decompensated. Fifty-three were Genotype 1, and 27 Genotype 3. Twenty-seven patients had history of previous failed interferon-based treatment. Three patients died in which cause of death was not related to treatment. Six patients were lost to follow-up. The remaining 94 patients all achieved SVR. No adverse events leading to discontinuation of medicine was observed. CONCLUSIONS: The combination of sofosbuvir and daclatasvir is an effective and safe treatment for patients infected with all genotypes of hepatitis C who have severe renal impairment, including patients on hemodialysis.

Metabolic Syndrome Is Associated with Health-Related Quality of Life in Suspected Patients with Nonalcoholic Steatohepatitis.

OBJECTIVE: This study was designed to examine the effect of metabolic syndrome (MetS) on health-related quality of life (HRQOL) in patients with suspected nonalcoholic steatohepatitis (NASH). SUBJECTS AND METHODS: Three hundred thirty-two patients (236 males and 96 females) with suspected NASH from the Amol cohort study were included in this study. MetS was diagnosed based on Adult Treatment Panel III criteria and HRQOL was measured using the 12-Item Short-Form Health Survey (SF-12) questionnaire (with 8 subscales and 2 summary components). A multivariable linear regression model was used to assess the independent effect of MetS on HRQOL. RESULTS: The mean age of the study population was 42 ± 13 years (range 18-82). The prevalence of MetS was 43.4% (n = 144) and the mean scores on the Physical Component Summary (PCS) and the Mental Component Summary were 72.4 ± 20.86 and 42.7 ± 12.42, respectively. The multivariable linear regression model showed that MetS was negatively associated with 4 subscales of HRQOL that included: role limitations due to physical problems (RP) (B = -14.05, p = 0.004), bodily pain (BP) (B = -7.37, p = 0.02), vitality (VT) (B = -7.72, p = 0.022), and role limitations due to emotional problems (RE) (B = -12.67, p = 0.005) after adjustment for other variables. Also, MetS had a borderline association with the general health and mental health subscales and the PCS (p < 0.1). CONCLUSION: In this study, there was a strong association between MetS and 4 subscales (RP, BP, VT, and RE) of HRQOL in patients with suspected NASH; this could be considered as a part of health policy to improve general health.

Pattern of body mass index, chronic diseases, and physical component of quality of life in a population in North of Iran: A latent class analysis.

Background: Due to the rise of non-communicable diseases (NCDs) and lifestyle changes, this study aimed at determining the subclasses of Iranian adults based on body mass index, some NCDs, and status of physical component of quality of life. Methods: A total of 5207 participants of Amol cohort study were studied in this study. Latent class analysis (LCA) was used to determine the best model with the minimum AIC or BIC. Results: We decided that the 6 latent classes model was the best model. The first class described 35.1% of the participants and was characterized by individuals with no disease status. The sixth class described 0.7% of the individuals and was characterized by individuals exhibiting high probability of body mass index (BMI) equal or more than 25, kidney inadequacy, hypertension, and moderate physical component of quality of life status. Conclusion: This study showed the pattern of body mass index, chronic diseases, and physical component of quality of life. Our findings demonstrated that some risk factors and non-communicable diseases tend to accumulate in some classes, especially classes 5 and 6, and thus the risk of developing these diseases rises along with increase in their clustering abilities. These results point out the critical importance of designing specific preventive interventional programs for these stratums of individuals.

Identifying the pattern of unhealthy dietary habits among an Iranian population: A latent class analysis.

Background: An unhealthy diet is one of the most important risk factors for chronic diseases. The goal of this study was to use the latent class analysis (LCA) modeling to define unhealthy diet habits among an Iranian population. Methods: This cross-sectional study was conducted within the framework of Amol (North of Iran) cohort health study (Phase 1). The participants aged 10 to 90 years. All participants provided written informed consent. Latent class analysis was used to classify the participants of the study. All analyses were conducted by PROC LCA in SAS 9.2 software. Significance level was set at 0.05. Results: The mean age of the participants was 42.58±17.23 years. Four classes of individuals with different diet habits were identified using LCA modeling: class 1: individuals with healthy diet patterns (92.6%); class 2: individuals with slightly unhealthy diet habits (6.3%); class 3: individuals with relatively unhealthy diet habits (0.8%); and class 4: individuals with unhealthy diet habits (0.2%). Being female and alcohol consumption increased the odds of membership in latent classes 2,3, and 4 compared to class 1. Physical activity decreased the odds of membership in classes 3 and 4 compared to class 1. Conclusion: Overall, almost more than 7.4% of all participants had some degree of unhealthy dietary habits, and some variables acted as risk factors for membership in risky classes. Therefore, focusing on these variables may help design and execute effective preventive interventions in groups with unhealthy dietary habits.

Application of the short form of quality of life instrument version 2 in a large population of Tehran.

Background: Quality of life (QoL) is now considered as a key indicator in health studies. Therefore, this study was conducted to evaluate QoL in the general population of Tehran (capital of Iran) using SF-12v2 questionnaire and determine some factors associated with it. Methods: This was part of a large population-based cross sectional study conducted in Tehran, Iran, in 2011. Participants were selected from all districts of Tehran using multistage cluster random sampling method. Data were collected using the Iranian version of the SF12v2 questionnaire. Linear regression model was used to assess the independent effect of surveyed variables of the study population on their QoL. P< 0.05 was considered statistically significant. Results: Overall, 30 809 individuals over the age of 20 from 22 urban districts were included in this study and evaluated by SF-12v2 questionnaire. The mean age of the study population was 44.5±15.9, and most of them were female (19 967 (64.8%)). The total mean score of SF-12v2 was 60.4 and the lowest and highest mean scores were observed in GH (46.9±26.5) and MH subscales (64.1±24.7), respectively. It was also observed that District 3 of Tehran had the highest mean score (65.2±18.7) in the total QoL and District 12 had the lowest mean score (56.6±18.7), respectively. The results of multiple linear regression model showed that sex, age, education, household size, presence of chronic disease in family, having insurance, smoking, and marital status were significantly related to most subscales and two summary components of QoL. Conclusion: The results of this study showed that the surveyed population of Tehran had a relatively moderate QoL, but it changed from district to district. It was also observed that age and education of the study population were important variables in relation to QoL.

Is household food insecurity a determinant of weight status in patients with type 2 diabetes in rural areas?

Background: There is mixed evidence about food insecurity and overweight/obesity coexisting, however it is unclear about association between food insecurity and weight status in people with type 2 diabetes. Therefore, the aim of this study was to evaluate the relationship between food insecurity and weight status in individuals with type 2 diabetes in rural areas in Iran. Methods: 1847 patients with type 2 diabetes who were residence in rural areas completed Household Food Security Scale (six-item short questionnaire). Logistic regression model was applied to assess the independent effect of food insecurity on weight status. Results: Mean age of the study population was 62.6±11.8 years, and the majority of them were female (70.4%). Most of the study population (70.4%) had unhealthy weight status. Food insecurity affected more than 46% (n=852) of the households of the study population. According to weight status, more than 40% (n=565) of overweight and obese subjects and 60% (n=18) of underweight subjects lived in households with food insecurity. The results of multiple logistic regression model showed that food insecurity was not an independent significant predictor of overweight or obesity in patients with type 2 diabetes. However, low food security (LFS) was an independent significant predictor for underweight in patients with type 2 diabetes (OR=2.35, P=0.041). Conclusion: It is concluded that food insecurity was frequent in all levels of weight status of patients with type 2 diabetes in rural regions. However this association observed in underweight individuals but there was no significant overall relationship between household food insecurity and in overweight and obesity in this group of patients.

Perianal Fistula; from Etiology to Treatment - A Review.

Anal fistula has been a challenging clinical issue for years due to its complex pathogenesis. The risk of frequent recurrence and incontinence complicates long-term treatment. Recent scientific literature has reviewed new techniques used for anal fistula treatment in recent years, assessing the advantages and disadvantages of each based on clinical outcomes. Although surgery is the main method used to treat anal fistula, there is no simple technique that can completely heal complex anal fistula. The surgical treatment should consider the healing outcome and the protection of anal function comprehensively. Several innovative techniques have emerged in recent years, such as combined techniques based on drainage seton and LIFT-plug, which appear to be relatively effective therapies. However, more multi-center prospective trials with long-term follow-up are needed to validate their effectiveness. In some situations, medical treatment may also be considered.