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Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss.
Pouwels, S, Sakran, N, Graham, Y, Leal, A, Pintar, T, Yang, W, Kassir, R, Singhal, R, Mahawar, K, Ramnarain, D
BMC endocrine disorders. 2022;(1):63
Abstract
Given the increasing prevalence of diabetes and obesity worldwide, the deleterious effects of non-alcoholic fatty liver disease (NAFLD) are becoming a growing challenge for public health. NAFLD is the most common chronic liver disease in the Western world. NAFLD is closely associated with metabolic disorders, including central obesity, dyslipidaemia, hypertension, hyperglycaemia and persistent abnormalities of liver function tests.In general NAFLD is a common denominer for a broad spectrum of damage to the liver, which can be due to hepatocyte injury, inflammatory processes and fibrosis. This is normally seen on liver biopsy and can range from milder forms (steatosis) to the more severe forms (non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis and liver failure). In these patients, advanced fibrosis is the major predictor of morbidity and liver-related mortality, and an accurate diagnosis of NASH and NAFLD is mandatory. Histologic evaluation with liver biopsy remains the gold standard to diagnose NAFLD. Diagnosis of NAFLD is defined as presence of hepatic steatosis, ballooning and lobular inflammation with or without fibrosis. Weight loss, dietary modification, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established. Dietary recommendations and lifestyle interventions, weight loss, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established with promising results but are difficult to maintain. Pioglitazone and vitamin E are recommended by guidelines in selected patients. This review gives an overview of NAFLD and its treatment options.
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Effects of liraglutide on visceral and ectopic fat in adults with overweight and obesity at high cardiovascular risk: a randomised, double-blind, placebo-controlled, clinical trial.
Neeland, IJ, Marso, SP, Ayers, CR, Lewis, B, Oslica, R, Francis, W, Rodder, S, Pandey, A, Joshi, PH
The lancet. Diabetes & endocrinology. 2021;(9):595-605
Abstract
BACKGROUND Visceral and ectopic fat are key drivers of adverse cardiometabolic outcomes in obesity. We aimed to evaluate the effects of injectable liraglutide 3·0 mg daily on body fat distribution in adults with overweight or obesity without type 2 diabetes at high cardiovascular disease risk. METHODS In this randomised, double-blind, placebo-controlled, phase 4, single centre trial, we enrolled community-dwelling adults, recruited from the University of Texas Southwestern Medical Center, with BMI of at least 30 kg/m2 or BMI of at least 27 kg/m2 with metabolic syndrome but without diabetes and randomly assigned them, in a 1:1 ratio, to 40 weeks of treatment with once-daily subcutaneous liraglutide 3·0 mg or placebo, in addition to a 500 kcal deficient diet and guideline-recommended physical activity counselling. The primary endpoint was percentage reduction in visceral adipose tissue (VAT) measured with MRI. All randomly assigned participants with a follow-up imaging assessment were included in efficacy analyses and all participants who received at least one dose of study drug were included in the safety analyses. The trial is registered on ClinicalTrials.gov: NCT03038620. FINDINGS Between July 20, 2017 and Feb 21, 2020 from 235 participants assessed for eligibility, 185 participants were randomly assigned (n=92 liraglutide, n=93 placebo) and 128 (n=73 liraglutide, n=55 placebo) were included in the final analysis (92% female participants, 37% Black participants, 24% Hispanic participants, mean age 50·2 years (SD 9·4), mean BMI 37·7 kg/m2). Mean change in VAT over median 36·2 weeks was -12·49% (SD 9·3%) with liraglutide compared with -1·63% (SD 12·3%) with placebo, estimated treatment difference -10·86% (95% CI -6·97 to -14·75, p<0·0001). Effects seemed consistent across subgroups of age, sex, race-ethnicity, BMI, and baseline prediabetes. The most frequently reported adverse events were gastrointestinal-related (43 [47%] of 92 with liraglutide and 12 [13%] of 93 with placebo) and upper respiratory tract infections (10 [11%] of 92 with liraglutide and 14 [15%] of 93 with placebo). INTERPRETATION In adults with overweight or obesity at high cardiovascular disease risk, once-daily liraglutide 3·0 mg plus lifestyle intervention significantly lowered visceral adipose tissue over 40 weeks of treatment. Visceral fat reduction may be one mechanism to explain the benefits seen on cardiovascular outcomes in previous trials with liraglutide among patients with type 2 diabetes. FUNDING NovoNordisk.
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Meta-analysis of trials in non-alcoholic fatty liver disease with therapeutic interventions for metabolic syndrome.
Albert, SG, Wood, EM
Diabetes & metabolic syndrome. 2021;(5):102232
Abstract
AIMS: Non-alcoholic fatty liver disease [NAFLD] is associated with metabolic syndrome [MS]. Current guidelines restrict therapy for NAFLD, other than weight loss, in early non-fibrotic disease. It was postulated that intervention with therapies for MS may improve liver fat content. METHODS A systematic evaluation of Cochrane and PubMed databases was performed for NAFLD or NASH if they were: 1) interventions for metabolic syndrome or diabetes mellitus 2) randomized controlled trials [RCT], with 3) primary outcomes of liver fat content [LFC] (by magnetic resonance spectroscopy [MRS] or liver biopsy (Nonalcoholic Fatty Liver Disease Activity Score [NAS]). RESULTS There were 30 RCT (in 24 publications) of 2409 subjects. LFC decreased with pioglitazone (MRS, -8.0 ± 1.0 %, p < 0.001), diet and exercise (-7.8 ± 1.7 %, p < 0.001) and omega-3 fatty acids (-6.0 ± 2.5 %, p = 0.02). Decreases in NAS scores were significant for pioglitazone (-1.4 ± 0.4 units, p < 0.001) and D&E (-1.0 ± 0.1 units, p < 0.001). Weight loss correlated with improvement in LFC (p < 0.001) and NAS (p < 0.001). Lowered serum triglycerides correlated with final LFC (p < 0.001) and NAS scores (p < 0.001). CONCLUSIONS Therapies of MS with weight loss, antiglycemic and triglyceride lowering medicines improved LFC and NAS scores. Further studies are necessary to demonstrate if these therapies would pre-emptively limit progression of disease.
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Diabetes Mellitus and COVID-19: Review Article.
Nassar, M, Daoud, A, Nso, N, Medina, L, Ghernautan, V, Bhangoo, H, Nyein, A, Mohamed, M, Alqassieh, A, Soliman, K, et al
Diabetes & metabolic syndrome. 2021;(6):102268
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Abstract
BACKGROUND AND AIMS We aim to cover most of the current evidence on the mutual effect of diabetes & COVID-19 infection on each other and the management of the COVID-19 patients with diabetes. METHODS We utilized databases to review the current evidence related to diabetes mellitus and COVID-19. RESULTS We discussed the most recent evidence of diabetes milieus and COVID-19 regarding risk factors, management, complications, and telemedicine. CONCLUSION Diabetes mellitus is associated with a significant risk of complications, extended hospital stays, and mortality in COVID-19 infected patients.
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Policaptil Gel Retard in adult subjects with the metabolic syndrome: Efficacy, safety, and tolerability compared to metformin.
Guarino, G, Della Corte, T, Strollo, F, Gentile, S, ,
Diabetes & metabolic syndrome. 2021;(3):901-907
Abstract
BACKGROUND Policaptil Gel Retard® (PGR), is a new macromolecule complex based on polysaccharides slowing the rate of carbohydrate and fat absorption. It proved to significantly reduce body weight, acanthosis nigricans expression, HbA1c levels, and glucose metabolism abnormalities in obese, hyper-insulinemic adolescents. No such data are available for adults. AIM: to compare the effects of PGR vs. metformin in adult subjects with the Metabolic Syndrome (MS) and T2DM on a Low Glycemic Index diet. SUBJECTS AND METHODS This spontaneous clinical, longitudinal, single-blind, randomized study based on a per-protocol analysis enrolled 100 outpatients with MS and T2DM consecutively referring to our clinic for three months, and randomly assigned to either the active treatment (Group A:, 6 tablets/day) or the comparator (Group B: Metformin tablets, 1500-2000 mg/day in two divided doses during the two main meals, to minimize side effects) to be taken 30 min before each main meal in equally divided doses. Serum lipid profile, anthropometry, HOMA-IR index, and tolerability parameters were evaluated before and after a 6-month follow-up period. RESULTS all parameters improved at a similar rate in both groups but for the lipid profile, which got even better in Group A. Group A also experienced less prominent gastrointestinal side effects than its counterpart. CONCLUSION For the first time, we showed the non-inferiority of PGR compared to metformin in obese adult subjects with the MS and T2DM as for glycemic control and a clear-cut superiority of PGR in terms of both serum lipid-lowering capacity and tolerability.
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The effects of myo-inositol vs. metformin on the ovarian function in the polycystic ovary syndrome: a systematic review and meta-analysis.
Azizi Kutenaei, M, Hosseini Teshnizi, S, Ghaemmaghami, P, Eini, F, Roozbeh, N
European review for medical and pharmacological sciences. 2021;(7):3105-3115
Abstract
OBJECTIVE Recent studies have revealed that myo-inositol could be more influential in patients with polycystic ovary syndrome (PCOS). This study was aimed to determine and compare the effects of myo-inositol and metformin on hormonal and metabolic profiles and fertility outcomes. MATERIALS AND METHODS A comprehensive search was carried out among the English-language databases, including PubMed, Scopus, Cochrane Library, Google Scholar, and Web of Science, and the articles published from April 2010 to February 2019 were tracked down. The fixed and random-effects meta-analysis was used to estimate the pooled effect size. The meta-analysis was performed in Stata Version 14.0. RESULTS Nine studies with 331 patients treated with metformin and 307 patients treated with myo-inositol groups were included in the analysis. The research groups did not diverge significantly in terms of the basic characteristics, such as age and Body Mass Index (BMI). In the myo-inositol group, the levels of Luteinizing Hormone (LH) [12.55% (95% I: 11.41-13.68%)], S. testosterone [44.38% (95% CI: 38.09-50.67%)] and prolactin [7.97% (95% CI: 6.58- 9.37%)] were significantly higher than those recorded, i.e., LH [7.97% (95% CI: 6.58- 9.37%)], S. testosterone [8.48% (95% CI: 3.14-13.83%)] and prolactin [7.14% (95% CI: 1.50-14.79%)] for the metformin group (p<0.001). CONCLUSIONS Due to the dearth of related research and the high heterogeneity of the Randomized Clinical Trials (RCTs) included in other studies, the present systematic review could not establish any differences between metformin and myo-inositol concerning the hormonal profile and the ovarian function. However, the findings indicated that myo-inositol could improve fertility outcomes by modulating hyperandrogenism. Randomized trials are required to understand the mechanistic actions of myo-inositol in comparison with those of metformin regarding oocyte and embryo quality, fertilization, pregnancy, and live birth rates.
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Impact of myoinositol with metformin and myoinositol alone in infertile PCOS women undergoing ovulation induction cycles - randomized controlled trial.
Prabhakar, P, Mahey, R, Gupta, M, Khadgawat, R, Kachhawa, G, Sharma, JB, Vanamail, P, Kumari, R, Bhatla, N
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2021;(4):332-336
Abstract
PURPOSE To evaluate the benefits of myoinositol plus metformin versus myoinositol alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction cycles. MATERIALS AND METHODS Total 116 infertile PCOS women were randomized: Group I (n = 57): metformin (1500 mg) plus myoinositol (4 g) per day; Group II (n=59): myoinositol 4 g per day. Subjects were advised to try for spontaneous conception. Those who did not conceive after three months were given three cycles of ovulation induction. Primary outcome was clinical pregnancy rate after 6 months. Secondary outcomes were improvement in metabolic and endocrine parameters, ongoing pregnancy, abortion and multiple pregnancy rate. RESULTS Baseline demographic, metabolic and hormonal parameters were comparable in two groups. After 3 months of therapy, both study groups had comparable improvement in metabolic and hormonal parameters. After 6 months, clinical pregnancy rate was 42.0% in Group I and 45.5% Group II respectively (RR 0.92(95% CI:0.60-1.43) (p > .05). Side-effects (mainly gastrointestinal) were significantly higher in Group I than group II. CONCLUSIONS Myoinositol (4 g) might be used alone as an insulin sensitizer to improve metabolic, hormonal and reproductive outcome in infertile PCOS women. Further studies with large numbers are warranted to confirm the role of myoinostiol as a sole insulin sensitizer.
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Integrated Network Pharmacology Analysis and Experimental Validation to Reveal the Mechanism of Anti-Insulin Resistance Effects of Moringa oleifera Seeds.
Huang, Q, Liu, R, Liu, J, Huang, Q, Liu, S, Jiang, Y
Drug design, development and therapy. 2020;:4069-4084
Abstract
BACKGROUND AND PURPOSE Insulin resistance (IR) is one of the factors that results in metabolic syndrome, type 2 diabetes mellitus and different aspects of cardiovascular diseases. Moringa oleifera seeds (MOS), traditionally used as an antidiabetic food and traditional medicine in tropical Asia and Africa, have exhibited potential effects in improving IR. To systematically explore the pharmacological mechanism of the anti-IR effects of MOS, we adopted a network pharmacology approach at the molecular level. METHODS By incorporating compound screening and target prediction, a feasible compound-target-pathway network pharmacology model was established to systematically predict the potential active components and mechanisms of the anti-IR effects of MOS. Biological methods were then used to verify the results of the network pharmacology analysis. RESULTS Our comprehensive systematic approach successfully identified 32 bioactive compounds in MOS and 44 potential targets of these compounds related to IR, as well as 37 potential pathways related to IR. Moreover, the network pharmacology analysis revealed that glycosidic isothiocyanates and glycosidic benzylamines were the major active components that improved IR by acting on key targets, such as SRC, PTPN1, and CASP3, which were involved in inflammatory responses and insulin-related pathways. Further biological research demonstrated that the anti-IR effects of MOS were mediated by increasing glucose uptake and modulating the expression of SRC and PTPN1. CONCLUSION Our study successfully predicts the active ingredients and potential targets of MOS for improving IR and helps to illustrate mechanism of action at a systemic level. This study not only provides new insights into the chemical basis and pharmacology of MOS but also demonstrates a feasible method for discovering potential drugs from traditional medicines.
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Gender difference in cardiovascular outcomes with SGLT-2 inhibitors and GLP-1 receptor agonist in type 2 diabetes: A systematic review and meta-analysis of cardio-vascular outcome trials.
Singh, AK, Singh, R
Diabetes & metabolic syndrome. 2020;(3):181-187
Abstract
BACKGROUND AND AIMS Type 2 diabetes confers a differential risk of cardiovascular (CV) disease according to the gender. Whether newly approved anti-diabetic drugs like sodium-glucose co-transport-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) that have shown a significant reduction in the CV end-points in CV outcome trials (CVOTs) also have a differential impact gender-wise, is still not clearly known. METHODS We systematically searched the medical database up to December 31, 2019 and retrieved all the dedicated CVOTs conducted with SGLT-2Is and GLP-1RAs that explicitly reported the outcome of major adverse cardiac events (MACE). Subsequently, we pooled the hazard ratio (HR) of MACE in both sexes separately and meta-analyzed the result gender-wise. RESULTS The meta-analysis of three CVOTs conducted with SGLT-2Is (N = 34,322), demonstrated a significant reduction in MACE in men but not in women (Men - HR, 0.90; 95% CI, 0.83 to 0.97; P = 0.006; Women - HR, 0.88; 95% CI, 0.77 to 1.00; P = 0.06) compared to placebo. The meta-analysis of seven CVOTs conducted with GLP-1RAs (N = 56,004) demonstrated a significant reduction in MACE in both sex (Men - HR, 0.88; 95% CI, 0.82 to 0.93; P < 0.0001; Women - HR, 0.88; 95% CI, 0.79 to 0.99; P = 0.03), against the placebo. CONCLUSIONS The reduction in MACE with SGLT-2Is appears to be significantly less in women with diabetes vs men, while GLP-1RAs confers a similar reduction in MACE, irrespective of the gender. Whether these results are related to inadequate statistical power (underrepresentation of women) in CVOT, or it reflects a true gender difference, still remains to be established.
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Clinical considerations in patients with diabetes during times of COVID19: An update on lifestyle factors and antihyperglycemic drugs with focus on India.
Gupta, R, Misra, A
Diabetes & metabolic syndrome. 2020;(6):1777-1781
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Abstract
BACKGROUND Diabetes is recognized as an important comorbidity in patients with COVID-19 and a large amount of literature has become available regarding this. The aim of this article is to review the literature regarding various aspects of association between diabetes and COVID-19 and to highlight clinically relevant points with focus on India. METHODS We searched Pubmed and Google Scholar databases for articles regarding diabetes and COVID-19 published between March 19, 2020 and August 30, 2020. RESULTS Diabetes and poor glycemic control are associated with increased severity and mortality in patients with COVID-19. Several clinical scenarios about hyperglycemia and COVID-19 are identified and each of these needs specific management strategies. CONCLUSION It is prudent to maintain good glycemic control in patients with diabetes in order to minimize the complications of COVID-19. There is a need for well conducted studies to asses the role of individual antihyperglycemic therapies in COVID-19 and also the behavior of new onset diabetes diagnosed either after COVID-19 infection or during this time.