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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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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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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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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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Reduced circulating levels of chemokine CXCL14 in adolescent girls with polycystic ovary syndrome: normalization after insulin sensitization.
García-Beltran, C, Cereijo, R, Quesada-López, T, Malpique, R, López-Bermejo, A, de Zegher, F, Ibáñez, L, Villarroya, F
BMJ open diabetes research & care. 2020;(1)
Abstract
OBJECTIVE CXCL14 (C-X-C motif chemokine ligand-14) is a chemokine released by active brown fat, showing protective effects against insulin resistance in experimental models. Polycystic ovary syndrome (PCOS) in adolescent girls is usually related to hepato-visceral fat excess and insulin resistance, and associates with comorbidities such as type 2 diabetes. Treatment with a low-dose combination of one antiandrogen and antimineralocorticoid drug (spironolactone) and two insulin sensitizers (pioglitazone/metformin) (SPIOMET) is particularly effective in improving these metabolic derangements. Adipose tissue may be involved in the metabolic alterations of PCOS, and it is a likely target of therapeutic action. We investigated the alterations in CXCL14 levels and the effects of drugs composing SPIOMET treatment on CXCL14 in human adipocytes. RESEARCH DESIGN AND METHODS We studied 51 adolescent patients with PCOS and 21 age-matched healthy controls. Thirty-one adolescent patients with PCOS under SPIOMET or oral contraception-based treatment were also studied. For studies in vitro, Simpson Golabi Behmel Syndrome (SGBS) adipose cells were used. Gene expression for CXCL14 and other genes was quantified using quantitative real-time PCR. The levels of CXCL14 and adipokines in serum and cell culture media were determined by ELISA. RESULTS Serum CXCL14 levels are reduced in patients with PCOS. One-year SPIOMET treatment normalized CXCL14 concentrations and improved the metabolic status of patients with PCOS. Pioglitazone induced CXCL14 expression in differentiating human SGBS adipocytes, in parallel with the induction of marker genes of brown adipogenesis. Spironolactone induced CXCL14 expression and release in differentiated human adipocytes. CONCLUSION Insulin sensitization with SPIOMET normalizes the abnormally low levels of CXCL14 in girls with PCOS. This is consistent with the effects of pioglitazone and spironolactone inducing CXCL14 expression and promoting a brown-like phenotype in adipocytes. CXCL14 may be a novel biomarker for PCOS as well as a potential mediator of the beneficial effects of the SPIOMET combination and may hold promise as a therapeutic modulator of the disorder. TRIAL REGISTRATION NUMBERS ISRCTN29234515 and ISCRCTN11062950.
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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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Can We Treat Neuroinflammation in Alzheimer's Disease?
Sánchez-Sarasúa, S, Fernández-Pérez, I, Espinosa-Fernández, V, Sánchez-Pérez, AM, Ledesma, JC
International journal of molecular sciences. 2020;(22)
Abstract
Alzheimer's disease (AD), considered the most common type of dementia, is characterized by a progressive loss of memory, visuospatial, language and complex cognitive abilities. In addition, patients often show comorbid depression and aggressiveness. Aging is the major factor contributing to AD; however, the initial cause that triggers the disease is yet unknown. Scientific evidence demonstrates that AD, especially the late onset of AD, is not the result of a single event, but rather it appears because of a combination of risk elements with the lack of protective ones. A major risk factor underlying the disease is neuroinflammation, which can be activated by different situations, including chronic pathogenic infections, prolonged stress and metabolic syndrome. Consequently, many therapeutic strategies against AD have been designed to reduce neuro-inflammation, with very promising results improving cognitive function in preclinical models of the disease. The literature is massive; thus, in this review we will revise the translational evidence of these early strategies focusing in anti-diabetic and anti-inflammatory molecules and discuss their therapeutic application in humans. Furthermore, we review the preclinical and clinical data of nutraceutical application against AD symptoms. Finally, we introduce new players underlying neuroinflammation in AD: the activity of the endocannabinoid system and the intestinal microbiota as neuroprotectors. This review highlights the importance of a broad multimodal approach to treat successfully the neuroinflammation underlying AD.
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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.
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Comparing the individual effects of metformin and rosiglitazone and their combination in obese women with polycystic ovary syndrome: a randomized controlled trial.
Li, Y, Tan, J, Wang, Q, Duan, C, Hu, Y, Huang, W
Fertility and sterility. 2020;(1):197-204
Abstract
OBJECTIVE To compare the effects of metformin, rosiglitazone, and their combination in obese polycystic ovary syndrome (PCOS) patients with insulin resistance. DESIGN Prospective randomized controlled trail. SETTING Tertiary teaching hospital. PATIENT(S): Obese Chinese women (body mass index [BMI] ≥25 kg/m2) with insulin resistance who fulfilled the Rotterdam criteria of PCOS. INTERVENTION(S): In group 1, 68 patients administered metformin (1,500 mg/day); in group 2, 67 patients administered rosiglitazone (4 mg/day); in group 3, 69 patients administered metformin (1,000 mg/day) and rosiglitazone (4 mg/day) for 6 months, all with the same diet and regular exercise lifestyle recommendation. MAIN OUTCOME MEASURE(S): Average menstrual interval, anthropometric measurements, androgen-related parameters, and metabolic features of insulin, carbohydrates, and lipids, with intention-to-treat analysis. RESULT(S): The baseline parameters showed no statistically significant differences. After the 6-month treatment, most participants showed an improved menstrual pattern. There were statistically significant decreases in acne scores, weight, BMI, waist circumference, waist-to-hip ratio, and serum testosterone. The metabolic indexes of insulin, carbohydrates, and lipids were improved obviously compared with the baseline in each group. Among the three groups, the patients administered 1,500 mg/day metformin experienced greater reductions in weight. However, the rosiglitazone users (alone or combined with metformin) showed a more notable decline in total cholesterol and triglyceride levels. CONCLUSION(S): Considering the benefits of metformin on weight loss, high-dose metformin (1,500 mg/day) along with lifestyle modification should be recommended for obese, insulin-resistant women with PCOS. Rosiglitazone alone or combined with low-dosage metformin plus lifestyle modification should be considered for the women with abnormal lipid profiles. CLINICAL TRIAL REGISTRATION NUMBER ChiCTR-TRC-13003642 (Chinese Clinical Trial Registry).
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Inhibition of the sodium-glucose co-transporter 2 in the elderly: clinical and mechanistic insights into safety and efficacy.
Cintra, R, Moura, FA, Carvalho, LSF, Barreto, J, Tambascia, M, Pecoits-Filho, R, Sposito, AC
Revista da Associacao Medica Brasileira (1992). 2019;(1):70-86
Abstract
The prevalence of type 2 diabetes mellitus (T2DM) in the elderly grew sharply over the last decade. Reduced insulin sensitivity and secretory capacity, weight gain, sarcopenia, and elevated adiposity are all common metabolic and body changes in the aging population that favor an increased risk of hypoglycemia, frailty syndrome, falls, and cognitive dysfunction. First line antidiabetic therapy is frequently not safe in older individuals because of its high risk of hypoglycemia and prevalent co-morbid diseases, such as chronic kidney disease, osteoporosis, cardiovascular disease, and obesity. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new class of antidiabetic therapy that inhibits glucose and sodium reabsorption on renal proximal convoluted tubule. Its effect is well demonstrated in various clinical scenarios in the younger population. This review and metanalysis describe particularities of the SGLT2i on the elderly, with mechanistic insights of the potential benefit and remaining challenges about the use of these drugs in this important age group. Further, we will present a meta-analysis of the main effects of SGLT2i reported in post-hoc studies in which the median age of the subgroups analyzed was over 60 years. Despite the absence of specific clinical trials for this population, our findings suggest that SGLT2i therapy on older individuals is effective to lower glucose and maintain its effect on systolic blood pressure and body weight.