Semaglutide for the management of diabesity: The real-world experience.

BACKGROUND: Diabesity (diabetes as a consequence of obesity) has emerged as a huge healthcare challenge across the globe due to the obesity pandemic. Judicious use of antidiabetic medications including semaglutide is important for optimal management of diabesity as proven by multiple randomized controlled trials. However, more real-world data is needed to further improve the clinical practice. AIM: To study the real-world benefits and side effects of using semaglutide to manage patients with diabesity. METHODS: We evaluated the efficacy and safety of semaglutide use in managing patients with diabesity in a large academic hospital in the United States. Several parameters were analyzed including demographic information, the data on improvement of glycated hemoglobin (HbA1c), body weight reduction and insulin dose adjustments at 6 and 12 months, as well as at the latest follow up period. The data was obtained from the electronic patient records between January 2019 to May 2023. RESULTS: 106 patients (56 males) with type 2 diabetes mellitus (T2DM), mean age 60.8 ± 11.2 years, mean durations of T2DM 12.4 ± 7.2 years and mean semaglutide treatment for 2.6 ± 1.1 years were included. Semaglutide treatment was associated with significant improvement in diabesity outcomes such as mean weight reductions from baseline 110.4 ± 24.6 kg to 99.9 ± 24.9 kg at 12 months and 96.8 ± 22.9 kg at latest follow up and HbA1c improvement from baseline of 82 ± 21 mmol/mol to 67 ± 20 at 12 months and 71 ± 23 mmol/mol at the latest follow up. An insulin dose reduction from mean baseline of 95 ± 74 units to 76.5 ± 56.2 units was also observed at the latest follow up. Side effects were mild and mainly gastrointestinal like bloating and nausea improving with prolonged use of semaglutide. CONCLUSION: Semaglutide treatment is associated with significant improvement in diabesity outcomes such as reduction in body weight, HbA1c and insulin doses without major adverse effects. Reviews of largescale real-world data are expected to inform better clinical practice decision making to improve the care of patients with diabesity.

Murraya koenigii (L.) Spreng. as a Natural Intervention for Diabesity: A Review.

BACKGROUND: Murraya koenigii (L.) Spreng. (family: Rutaceae), commonly known as curry leaf or sweet neem, is a tropical plant native to India and Southeast Asia. It is highly valued in Ayurveda for its medicinal properties. Almost every part (fresh leaves, fruits, bark, and roots) of this plant is used to treat various ailments. Its fresh leaves are considered to have numerous medicinal properties for various diseases, including piles, inflammation, itching, fresh cuts, dysentery, and edema. A combination of curry leaf and buttermilk is used to treat diseases, such as amoebiasis, diabetes, and hepatitis. Its leaves are also believed to possess antioxidant, anti-inflammatory, and antimicrobial properties. The bark has been traditionally used for treating snakebites. Its roots are utilized in Ayurveda for the treatment of body aches. Being a storehouse of carbazole alkaloids, M. koenigii has been reported to show anti-obesity and anti-diabetic activity in in vitro and in vivo studies. The review aimed to appraise the role of M. koenigii leaf in the prevention of diabesity. METHODS: We performed a literature search with the keywords "diabesity", "obesity", "diabetes", "adipose tissue", and "carbazole alkaloids" on Google Scholar, PubMed, and ScienceDirect databases. Several in vitro and in vivo studies conducted on cell lines and animals for anti-diabetic/anti-hyperglycemic and antihyperlipidemic activities have been included and appraised in the article, providing supporting evidence for the ethnomedicinal claims. RESULTS AND CONCLUSION: This review has been an attempt to summarize comprehensively the overall research done on M. koenigii with regard to obesity and diabetes. The studies on anti-diabetic/anti-hyperglycemic and anti-hyperlipidemic activities of the plant have ranged from studies on crude extracts to isolated compounds. However, some of the studies require further in-depth analysis and validation of obtained results.

Assessment of the Liver Steatosis and Fibrosis Risk in Metabolic Syndrome and Its Individual Components, Considering the Varying Definitions Used in Clinical Practice throughout Time: A Retrospective Cross-Sectional Study.

Multiple modifications of metabolic syndrome diagnostic criteria have been made-NCEP: ATP III (from 2001, modified in 2004), IDF (2005), IDF Consortium (2009), or Polish Scientific Society Consortium standards (2022) are now frequently in use. Hepatosteatosis and hepatofibrosis are commonly mentioned aspects of metabolic syndrome that greatly increase the likelihood of developing complications. The objective of the study was to assess different diagnostic criteria for metabolic syndrome based on the prevalence of liver steatosis and fibrosis. A retrospective analysis was conducted on the medical data of 2102 patients. Out of all the single criteria, meeting the obesity criterion based on waist circumference showed the highest increase in the risk of hepatosteatosis (by 64-69%, depending on the definition used)-hypertriglyceridemia increased the risk of hepatofibrosis by 71%. Regardless of the specific criteria used, patients with metabolic syndrome had a 34-36% increased likelihood of developing hepatosteatosis-the probability of hepatofibrosis varied between 42% and 47% for the criteria established in 2004, 2005, and 2009, while the Polish 2022 criteria were not statistically significant (p = 0.818). It seems appropriate to establish consistent metabolic syndrome diagnostic criteria-the 2009 IDF guidelines are the most effective in assessing hepatosteatosis and fibrosis risk.

The KgA1c Paradox: Widening the spectrum.

The term KgA1c paradox is used to describe the unwanted rise in weight that occurs when HbA1c is controlled using conventional therapy. We highlight facets of pathophysiology, prevention, pharmacology, person centred care, and epidemiology, which correspond to the concept of KgA1c paradox. We suggest a novel index, KgA1c product [(BMI) x (HbA1c)], which can be used to evaluate efficacy of drugs, and assess metabolic control in persons with diabetes.

Effects of Low and High Doses of Aspirin on Inflammatory Markers in Diabesity Patients: A Quasi-Experimental Study.

Introduction The intertwined nature of obesity and diabetes, termed diabesity, is a significant health concern. Aspirin has been recognized for its potential in mitigating inflammation-related health issues, a key concern in managing diabesity. However, the optimal aspirin dosage and its impact on specific inflammatory markers, viz. high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, over time remain a subject of ongoing research. Objective This study investigated the effects of different doses of aspirin (150mg and 300mg) on the levels of hs-CRP and IL-6 over a period of 6 months. Methods This cross-sectional observational quasi-experiment study involved 125 confirmed type-2 diabetes mellitus (T2DM) patients with obesity aged ≥40 years. Blood samples were collected for analyzing hs-CRP and IL-6 levels. Demographics and clinical characteristics, such as BMI, waist-hip ratio, blood parameters, fasting blood sugar (FBS), and hs-CRP, were analyzed. Results At baseline, both the 150 mg and 300 mg aspirin dose groups had similar median levels of hs-CRP. After two months, there was no significant difference (p=0.150). However, by six months, the 150mg dose group had a significantly higher median hs-CRP than the 300 mg dose group (p=0.003). The 150 mg dose group had a significantly higher median level of IL-6 levels at baseline (median; 40.0) compared to the 300 mg dose group (median; 2.27, p<0.0001). After two months, the levels of IL-6 in both groups were similar (median; 2.27 and 2.23 respectively, p<0.0001). By the end of six months, the groups had no significant difference (median; 0.53 and 2.22 respectively, p=0.128). Conclusion The dose of aspirin may significantly impact the levels of hs-CRP and IL-6 over time, with the effects being more pronounced after six months of treatment. These findings suggest that aspirin, a commonly used and cost-effective medication, could potentially be leveraged in a more targeted manner to manage inflammation (CRP and IL-6 levels) in individuals with diabesity.

Long-term exposure to PM2.5 chemical constituents and diabesity: evidence from a multi-center cohort study in China.

Background: Long-term exposure to PM2.5 is known to increase the risks for diabetes and obesity, but its effects on their coexistence, termed diabesity, remain uncertain. This study aimed to investigate the associations of long-term exposure to PM2.5 and its chemical constituents with the risks for diabesity, diabetes, and obesity. Methods: This cross-sectional study used the baseline data of a multi-center cohort, consisting of three provincially representative cohorts comprising a total of 134,403 participants from the eastern (Fujian Province), central (Hubei Province), and western (Yunnan Province) regions of China. Obesity and diabetes, and diabesity were identified by a body mass index (BMI) ≥28 kg/m2 and fasting plasma glucose (FPG) ≥126 mg/dL. The average concentrations of PM2.5 and five chemical constituents (NO3 -, SO4 2-, NH4 +, organic matter, and black carbon) over participants' residence during the past three years were estimated using machine learning models. Logistic regression models with double robust estimators, Bayesian kernel machine regression, and weighted quantile sum regression were employed to estimate independent and joint effects of PM2.5 chemical constituents on the risks for diabesity, diabetes, and obesity, as well as the differences from the effects on obesity. Stratified analyses were performed to examine effect modification of sociodemographic and lifestyle factors. Findings: There were 129,244 participants with a mean age of 54.1 ± 13.8 years included in the study. Each interquartile range increase in PM2.5 concentration (8.53 µg/m3) was associated with an increased risk for diabesity (OR = 1.23 [1.17, 1.30]), diabetes only (OR = 1.16 [1.13, 1.19]), and obesity only (OR = 1.03 [1.00, 1.05]). Long-term exposure to each PM2.5 chemical constituent was associated with an increased risk for diabesity, where organic matter exposure, with maximum weight (48%), was associated with a higher risk for diabesity (OR = 1.21 [1.16, 1.27]). Among those with obesity, black carbon contributed most (68%) to the joint effect of PM2.5 chemical constituents on diabesity (OR = 1.16 [1.11, 1.22]). Physical activity reduced adverse effects of PM2.5 on diabesity. Also, additive rather than multiplicative effects of obesity on the PM2.5-diabetes association were observed. Interpretation: Long-term exposure to PM2.5 and its chemical constituents was associated with an increased risk for diabesity, stronger than associations for diabetes and obesity alone. The main constituents associated with diabesity and obesity were black carbon and organic matter. Funding: National Natural Science Foundation of China (42271433, 723B2017), National Key R&D Program of China (2023YFC3604702), Fundamental Research Funds for the Central Universities (2042023kfyq04, 2042024kf1024), the Science and Technology Major Project of Tibetan Autonomous Region of China (XZ202201ZD0001G), Science and technology project of Tibet Autonomous Region（XZ202303ZY0007G), Key R&D Project of Sichuan Province (2023YFS0251), Renmin Hospital of Wuhan University (JCRCYG-2022-003), Jiangxi Provincial 03 Special Foundation and 5G Program (20224ABC03A05), Wuhan University Specific Fund for Major School-level Internationalization Initiatives (WHU-GJZDZX-PT07).

Comprehensive Strategies for Metabolic Syndrome: How Nutrition, Dietary Polyphenols, Physical Activity, and Lifestyle Modifications Address Diabesity, Cardiovascular Diseases, and Neurodegenerative Conditions.

Several hallmarks of metabolic syndrome, such as dysregulation in the glucose and lipid metabolism, endothelial dysfunction, insulin resistance, low-to-medium systemic inflammation, and intestinal microbiota dysbiosis, represent a pathological bridge between metabolic syndrome and diabesity, cardiovascular, and neurodegenerative disorders. This review aims to highlight some therapeutic strategies against metabolic syndrome involving integrative approaches to improve lifestyle and daily diet. The beneficial effects of foods containing antioxidant polyphenols, intestinal microbiota control, and physical activity were also considered. We comprehensively examined a large body of published articles involving basic, animal, and human studie, as well as recent guidelines. As a result, dietary polyphenols from natural plant-based antioxidants and adherence to the Mediterranean diet, along with physical exercise, are promising complementary therapies to delay or prevent the onset of metabolic syndrome and counteract diabesity and cardiovascular diseases, as well as to protect against neurodegenerative disorders and cognitive decline. Modulation of the intestinal microbiota reduces the risks associated with MS, improves diabetes and cardiovascular diseases (CVD), and exerts neuroprotective action. Despite several studies, the estimation of dietary polyphenol intake is inconclusive and requires further evidence. Lifestyle interventions involving physical activity and reduced calorie intake can improve metabolic outcomes.

Rising tide: The global surge of type 2 diabetes in children and adolescents demands action now.

Childhood-onset obesity has emerged as a major public healthcare challenge across the globe, fueled by an obesogenic environment and influenced by both genetic and epigenetic predispositions. This has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and adolescents. The looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most countries. Unless there is a collective global effort to curb the devastation caused by the situation, the impact is poised to be pro-found. A multifaceted research effort, governmental legislation, and effective social action are crucial in attaining this goal. This article delves into the current epidemiological landscape, explores evidence concerning potential risks and consequences, delves into the pathobiology of childhood obesity, and discusses the latest evidence-based management strategies for diabesity.

Mechanisms of spinophilin-dependent pancreas dysregulation in obesity.

Spinophilin is an F-actin binding and protein phosphatase 1 (PP1) targeting protein that acts as a scaffold of PP1 to its substrates. Spinophilin knockout (Spino-/-) mice have decreased fat mass, increased lean mass, and improved glucose tolerance, with no difference in feeding behaviors. Although spinophilin is enriched in neurons, its roles in nonneuronal tissues, such as ß cells of the pancreatic islets, are unclear. We have corroborated and expanded upon previous studies to determine that Spino-/- mice have decreased weight gain and improved glucose tolerance in two different models of obesity. We have identified multiple putative spinophilin-interacting proteins isolated from intact pancreas and observed increased interactions of spinophilin with exocrine, ribosomal, and cytoskeletal protein classes that normally act to mediate peptide hormone production, processing, and/or release in Leprdb/db and/or high-fat diet-fed (HFF) models of obesity. In addition, we have found that spinophilin interacts with proteins from similar classes in isolated islets, suggesting a role for spinophilin in the pancreatic islet. Consistent with a pancreatic ß cell type-specific role for spinophilin, using our recently described conditional spinophilin knockout mice, we found that loss of spinophilin specifically in pancreatic ß cells improved glucose tolerance without impacting body weight in chow-fed mice. Our data further support the role of spinophilin in mediating pathophysiological changes in body weight and whole body metabolism associated with obesity. Our data provide the first evidence that pancreatic spinophilin protein interactions are modulated by obesity and that loss of spinophilin specifically in pancreatic ß cells impacts whole body glucose tolerance.NEW & NOTEWORTHY To our knowledge, these data are the first to demonstrate that obesity impacts spinophilin protein interactions in the pancreas and identify spinophilin specifically in pancreatic ß cells as a modulator of whole body glucose tolerance.

Advancements in the management of obesity: a review of current evidence and emerging therapies.

INTRODUCTION: Obesity is the modern world's current epidemic, with substantial health and economic impact. This study aimed to provide a narrative overview of the past, currently available, and future treatment options that offer therapeutic and preventive advantages for obesity management. AREAS COVERED: Historically, rimonabant, and lorcaserin, were approved and used for managing non-syndromic obesity. Currently, orlistat, naltrexone/bupropion, glucagon-like peptide-1 receptor agonist (GLP-1 RA), and a few promising therapeutic agents are under investigation, including retatrutide, cagrilintide and orforglipron, which show promising weight reduction effects. We have developed a search string of the Medical Subject Headings (MeSH), including the terms GLP-1 RAs, obesity, and weight loss. This string was then used to perform a systematic literature search in the database including PubMed, EMBASE, MEDLINE, and Scopus up to January 31st, 2024. EXPERT OPINION: Managing obesity often requires medical interventions, particularly in cases of severe obesity or obesity-related comorbidities. Thus, it is important to approach obesity management holistically, considering individual needs and circumstances. In our opinion, consulting with healthcare professionals is crucial to developing a personalized plan that addresses both weight loss and overall health improvement.

Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus: A real-world experience.

BACKGROUND: Sodium glucose cotransporter-2 inhibitors (SGLT-2i) are a class of drugs with modest antidiabetic efficacy, weight loss effect, and cardiovascular benefits as proven by multiple randomised controlled trials (RCTs). However, real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse. AIM: To study the comparative efficacy and safety of SGLT-2i using real-world clinical data. METHODS: We evaluated the comparative efficacy data of 3 SGLT-2i drugs (dapagliflozin, canagliflozin, and empagliflozin) used for treating patients with type 2 diabetes mellitus. Data on the reduction of glycated hemoglobin (HbA1c), body weight, blood pressure (BP), urine albumin creatinine ratio (ACR), and adverse effects were recorded retrospectively. RESULTS: Data from 467 patients with a median age of 64 (14.8) years, 294 (62.96%) males and 375 (80.5%) Caucasians were analysed. Median diabetes duration was 16.0 (9.0) years, and the duration of SGLT-2i use was 3.6 (2.1) years. SGLT-2i molecules used were dapagliflozin 10 mg (n = 227; 48.6%), canagliflozin 300 mg (n = 160; 34.3%), and empagliflozin 25 mg (n = 80; 17.1). Baseline median (interquartile range) HbA1c in mmol/mol were: dapagliflozin - 78.0 (25.3), canagliflozin - 80.0 (25.5), and empagliflozin - 75.0 (23.5) respectively. The respective median HbA1c reduction at 12 months and the latest review (just prior to the study) were: 66.5 (22.8) & 69.0 (24.0), 67.0 (16.3) & 66.0 (28.0), and 67.0 (22.5) & 66.5 (25.8) respectively (P < 0.001 for all comparisons from baseline). Significant improvements in body weight (in kilograms) from baseline to study end were noticed with dapagliflozin - 101 (29.5) to 92.2 (25.6), and canagliflozin 100 (28.3) to 95.3 (27.5) only. Significant reductions in median systolic and diastolic BP, from 144 (21) mmHg to 139 (23) mmHg; (P = 0.015), and from 82 (16) mmHg to 78 (19) mmHg; (P < 0.001) respectively were also observed. A significant reduction of microalbuminuria was observed with canagliflozin only [ACR 14.6 (42.6) at baseline to 8.9 (23.7) at the study end; P = 0.043]. Adverse effects of SGLT-2i were as follows: genital thrush and urinary infection - 20 (8.8%) & 17 (7.5%) with dapagliflozin; 9 (5.6%) & 5 (3.13%) with canagliflozin; and 4 (5%) & 4 (5%) with empagliflozin. Diabetic ketoacidosis was observed in 4 (1.8%) with dapagliflozin and 1 (0.63%) with canagliflozin. CONCLUSION: Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c, body weight, and better than those reported in RCTs, with low side effect profiles. A review of large-scale real-world data is needed to inform better clinical practice decision making.

From classical dualistic antagonism to hormone synergy: potential of overlapping action of glucagon, insulin and GLP-1 for the treatment of diabesity.

The increasing prevalence of 'diabesity', a combination of type 2 diabetes and obesity, poses a significant global health challenge. Unhealthy lifestyle factors, including poor diet, sedentary behaviour, and high stress levels, combined with genetic and epigenetic factors, contribute to the diabesity epidemic. Diabesity leads to various significant complications such as cardiovascular diseases, stroke, and certain cancers. Incretin-based therapies, such as GLP-1 receptor agonists and dual hormone therapies, have shown promising results in improving glycaemic control and inducing weight loss. However, these therapies also come with certain disadvantages, including potential withdrawal effects. This review aims to provide insights into the cross-interactions of insulin, glucagon, and GLP-1, revealing the complex hormonal dynamics during fasting and postprandial states, impacting glucose homeostasis, energy expenditure, and other metabolic functions. Understanding these hormonal interactions may offer novel hypotheses in the development of 'anti-diabesity' treatment strategies. The article also explores the question of the antagonism of insulin and glucagon, providing insights into the potential synergy and hormonal overlaps between these hormones.

Amylin, Another Important Neuroendocrine Hormone for the Treatment of Diabesity.

Diabetes mellitus is a devastating chronic metabolic disease. Since the majority of type 2 diabetes mellitus patients are overweight or obese, a novel term-diabesity-has emerged. The gut-brain axis plays a critical function in maintaining glucose and energy homeostasis and involves a variety of peptides. Amylin is a neuroendocrine anorexigenic polypeptide hormone, which is co-secreted with insulin from ß-cells of the pancreas in response to food consumption. Aside from its effect on glucose homeostasis, amylin inhibits homeostatic and hedonic feeding, induces satiety, and decreases body weight. In this narrative review, we summarized the current evidence and ongoing studies on the mechanism of action, clinical pharmacology, and applications of amylin and its analogs, pramlintide and cagrilintide, in the field of diabetology, endocrinology, and metabolism disorders, such as obesity.

Gut microbiome as therapeutic target for diabesity management: opportunity for nanonutraceuticals and associated challenges.

Diabesity is showing rising prevalence. Current treatment modalities include pharmacological and non-pharmacological approaches, yet associated with various drawbacks. Recently, gut microbial dysbiosis is documented as a crucial factor in the pathogenesis of diabesity. Targeting gut microbiome using modulators shows promising therapeutic strategy for diabesity management. In this line, nanonutraceuticals represent new class of gut microbial modulators. The present article explores the potential of nanonutraceuticals including nanoprobiotics, nanoprebiotics, and plant-derived nanovesicles that are fabricated on the ecofriendly food based scaffold with gut microbial modulatory potential for diabesity management. A number of compelling evidences from different studies support Bifidobacterium, Enterococcus, and Bacteroides genera and Lactobacillus plantarum and Akkermansia muciniphila species significant in diabesity management. The probable mechanisms reported for gut microbial dysbiosis-induced diabesity are mentioned. The review findings suggest gut microbiome as significant therapeutic target for diabesity management. Moreover, ecofriendly nanonutraceuticals developed using natural products including food-grade materials are efficient modulators of gut microbiome and indicate next-generation diabesity therapeutics. Clinical studies are imperative as further exploration may provide new dimensions to the future research.

Diabesity phenotype in relation to the incidence and resolution of nonalcoholic fatty liver disease: A prospective cohort study.

BACKGROUND: Diabesity is a term used to emphasize the dual epidemic and the combined detrimental effects of diabetes and obesity. We aimed to investigate the associations of diabesity with the incidence and resolution of nonalcoholic fatty liver disease (NAFLD). METHODS: This prospective cohort study included 5549 participants with a median follow-up of 4.3 years (2010-2015). Diabesity was defined as six categories by the combinations of glucose tolerance status (normal glucose tolerance [NGT], prediabetes, and diabetes) diagnosed by fasting and oral glucose tolerance test 2-h glucose and hemoglobin A1c and general or abdominal obesity status. We examined the odds ratios (ORs) for the incidence and resolution of NAFLD associated with diabesity categories, respectively. RESULTS: For NAFLD incidence, compared with the diabesity category of NGT with nonobesity, the categories of either glucose intolerance or general obesity were associated with higher risks of NAFLD, of which the categories with obesity, regardless of glucose intolerance status, exhibited greater risks (ORs ranged from 3.19 to 4.49) than the categories of nonobesity. For NAFLD resolution, the categories of prediabetes or diabetes with obesity were associated with decreased likelihoods of a resolution of NAFLD (ORs ranged from 0.40 to 0.58). These association patterns were consistent across various definitions of diabesity by glucose tolerance status diagnosed by different combinations of glycemic parameters and general or abdominal obesity. CONCLUSIONS: The diabesity association pattern with NAFLD incidence was mainly determined by obesity, while that with NAFLD resolution was driven by the combined phenotype of glucose intolerance and obesity.

Metabolic Syndrome: A Narrative Review from the Oxidative Stress to the Management of Related Diseases.

Metabolic syndrome (MS) is a growing disorder affecting thousands of people worldwide, especially in industrialised countries, increasing mortality. Oxidative stress, hyperglycaemia, insulin resistance, inflammation, dysbiosis, abdominal obesity, atherogenic dyslipidaemia and hypertension are important factors linked to MS clusters of different pathologies, such as diabesity, cardiovascular diseases and neurological disorders. All biochemical changes observed in MS, such as dysregulation in the glucose and lipid metabolism, immune response, endothelial cell function and intestinal microbiota, promote pathological bridges between metabolic syndrome, diabesity and cardiovascular and neurodegenerative disorders. This review aims to summarise metabolic syndrome's involvement in diabesity and highlight the link between MS and cardiovascular and neurological diseases. A better understanding of MS could promote a novel strategic approach to reduce MS comorbidities.

Prevalence and Crucial Parameters in Diabesity-Related Liver Fibrosis: A Preliminary Study.

Diabetes and obesity have been recognized as confirmed risk factors for the occurrence of liver fibrosis. Despite the long-standing acknowledgment of "diabesity", the simultaneous existence of diabetes and obesity, scholarly literature has shown limited attention to this topic. The aim of this pilot study was to assess the prevalence of liver fibrosis among individuals with diabetes (specifically those who are obese) in order to identify the key factors associated with hepatofibrosis and determine the most important associations and differences between patients with and without liver fibrosis. The research included a total of 164 participants (48.17% had comorbid obesity). Liver elastography (Fibroscan) was performed on these individuals in addition to laboratory tests. Liver fibrosis was found in 34.76% of type 2 diabetes patients; male gender almost doubled the risk of hepatofibrosis (RR 1.81) and diabesity nearly tripled this risk (RR 2.81; however, in degree III of obesity, the risk was elevated to 3.65 times higher). Anisocytosis, thrombocytopenia, or elevated liver enzymes raised the incidence of liver fibrosis by 1.78 to 2.47 times. In these individuals, liver stiffness was negatively correlated with MCV, platelet count, and albumin concentration; GGTP activity and HbA1c percentage were positively correlated. The regression analysis results suggest that the concentration of albumin and the activity of GGTP are likely to have a substantial influence on the future management of liver fibrosis in patients with diabesity. The findings of this study can serve as the basis for subsequent investigations and actions focused on identifying potential therapeutic and diagnostic avenues.

Diabetes and diabesity in the view of proteomics, drug, and plant-derived remedies.

Diabetes and obesity are highly prevalent in the world. Proteomics is a promising approach to better understanding enzymes, proteins, and signaling molecules involved in diabetes processes which help recognize the basis of the disease better and find suitable new treatments. This study aimed to summarize the molecular mechanisms from the beginning of insulin secretion in response to stimuli to the pathology of the insulin signaling pathway and, finally, the mechanisms of drugs/chemicals remedies that affect this process. The titles and subtitles of this process were determined, and then for each of them, the articles searched in PubMed and ScienceDirect were used. This review article starts the discussion with the molecular basis of insulin biosynthesis, secretion, insulin's mechanism of action, and molecular aspect of diabetes and diabesity (a new term showing the relation between diabetes and obesity) and ends with the drug and plant-derived intervention for hyperglycemia.

Melatonin Improves Skeletal Muscle Structure and Oxidative Phenotype by Regulating Mitochondrial Dynamics and Autophagy in Zücker Diabetic Fatty Rat.

Obesity-induced skeletal muscle (SKM) inflexibility is closely linked to mitochondrial dysfunction. The present study aimed to evaluate the effects of melatonin on the red vastus lateralis (RVL) muscle in obese rat models at the molecular and morphological levels. Five-week-old male Zücker diabetic fatty (ZDF) rats and their age-matched lean littermates (ZL) were orally treated either with melatonin (10 mg/kg body weight (BW)/24 h) (M-ZDF and M-ZL) or non-treated (control) (C-ZDF and C-ZL) for 12 weeks. Western blot analysis showed that mitochondrial fission, fusion, and autophagy were altered in the C-ZDF group, accompanied by reduced SIRT1 levels. Furthermore, C-ZDF rats exhibited depleted ATP production and nitro-oxidative stress, as indicated by increased nitrites levels and reduced SOD activity. Western blotting of MyH isoforms demonstrated a significant decrease in both slow and fast oxidative fiber-specific markers expression in the C-ZDF group, concomitant with an increase in the fast glycolytic fiber markers. At the tissue level, marked fiber atrophy, less oxidative fibers, and excessive lipid deposition were noted in the C-ZDF group. Interestingly, melatonin treatment partially restored mitochondrial fission/fusion imbalance in the RVL muscle by enhancing the expression of fission (Fis1 and DRP1) markers and decreasing that of fusion (OPA1 and Mfn2) markers. It was also found to restore autophagy, as indicated by increased p62 protein level and LC3BII/I ratio. In addition, melatonin treatment increased SIRT1 protein level, mitochondrial ATP production, and SOD activity and decreased nitrites production. These effects were associated with enhanced oxidative phenotype, as evidenced by amplified oxidative fiber-specific markers expression, histochemical reaction for NADH enzyme, and muscular lipid content. In this study, we showed that melatonin might have potential therapeutic implications for obesity-induced SKM metabolic inflexibility among patients with obesity and T2DM.

Fetoplacental endothelial dysfunction in gestational diabetes mellitus and maternal obesity: A potential threat for programming cardiovascular disease.

Gestational diabetes mellitus (GDM) and maternal obesity (MO) increase the risk of adverse fetal outcomes, and the incidence of cardiovascular disease later in life. Extensive research has been conducted to elucidate the underlying mechanisms by which GDM and MO program the offspring to disease. This review focuses on the role of fetoplacental endothelial dysfunction in programming the offspring for cardiovascular disease in GDM and MO pregnancies. We discuss how pre-existing maternal health conditions can lead to vascular dysfunction in the fetoplacental unit and the fetus. We also examine the role of fetoplacental endothelial dysfunction in impairing fetal cardiovascular system development and the involvement of nitric oxide and hydrogen sulfide in mediating fetoplacental vascular dysfunction. Furthermore, we suggest that the L-Arginine-Nitric Oxide and the Adenosine-L-Arginine-Nitric Oxide (ALANO) signaling pathways are pertinent targets for research. Despite significant progress in this area, there are still knowledge gaps that need to be addressed in future research.