Diabesity, the concurrent occurrence of obesity and type-2 diabetes mellitus (T2DM), represents a pressing global health challenge characterized by intricate pathophysiological mechanisms and a wide range of associated comorbidities. Central to its development are insulin resistance, metabolic syndrome, and chronic low-grade inflammation mediated by dysregulated adipokine secretion and systemic metabolic dysfunction. These mechanisms underpin the progression of diabesity and its complications, including cardiovascular disease and hypertension. Management strategies encompass lifestyle interventions focusing on tailored dietary modifications and structured physical activity, pharmacological treatments targeting both glycemic control and weight loss, and surgical interventions such as bariatric surgery, which have demonstrated efficacy in achieving durable outcomes. Clinical trials and meta-analyses underscore the comparative advantages of different treatment modalities in terms of efficacy, safety, and sustainability. Moreover, long-term follow-up studies emphasize the critical need for sustained multidisciplinary interventions to prevent relapse and enhance patient outcomes. Future advancements in management include exploring precision medicine approaches that integrate individual metabolic profiles, lifestyle factors, and emerging therapeutic innovations. A multidisciplinary approach combining advanced therapeutic strategies and patient-centered care remains pivotal for optimizing management and improving prognoses for individuals with diabesity. This review highlights the complex interplay between obesity and T2DM, offering comprehensive insights into their pathophysiology, clinical presentation, and management paradigms.

Despite the recognition by key guidelines that achieving early glycaemic control has important benefits in individuals with type 2 diabetes (T2D) and that addressing excess adiposity is one of the central components of comprehensive person-centred T2D care, a substantial proportion of individuals with T2D do not meet their metabolic treatment goals. Prior treatment paradigms were limited by important treatment-associated risks such as hypoglycaemia and body weight gain. Therefore, a more conservative, sequential approach to treatment was typically utilized. One potential consequence of this approach has been a missed opportunity to achieve a 'legacy effect', where early treatment to reach glycaemic targets is associated with enduring long-term benefits in T2D. Additionally, while previous treatment approaches have addressed core defects in T2D, including insulin resistance and β-cell function decline, they have been unable to address one of the underlying causal abnormalities-excess adiposity. Here, we review currently available evidence for the beneficial long-term effects of early glycaemic control and management of body weight in people with T2D and discuss potential next steps.

The prevalence of obesity has increased significantly in recent years and is a causal risk factor for the development of type 2 diabetes. Moreover, chronic degenerative joint diseases are also triggered by obesity.

Both obesity-related secondary diseases-type 2 diabetes and chronic degenerative joint disease-can be prevented or at least delayed by lifestyle intervention aimed at weight reduction. The progression of these diseases can also be favourably influenced by radical weight loss. Diets with a reduction in carbohydrates-a so-called "low-carb" or ketogenic diet-appear to be superior to a low-fat diet.

If joint replacement surgery is necessary, preoperative and perioperative interdisciplinary care by a team of experienced therapists from the fields of orthopaedics and obesity/type 2 diabetes is required. The Düsseldorf TeDia model in the network of Catholic hospitals in Düsseldorf takes these requirements into account by providing interdisciplinary care for such patients at the orthopaedic centre at St. Vinzenz Hospital Düsseldorf and the West German Diabetes and Health Centre (WDGZ). Patients with pronounced obesity or diabetes mellitus are presented preoperatively at the WDGZ on an outpatient basis, and weight reduction therapy or optimization of the diabetic metabolic situation is initiated. If joint problems persist despite weight reduction or pronounced degenerative changes that require surgery, the WDGZ provides inpatient diabetology care in the orthopaedic clinic with the option of further outpatient follow-up care.

diabesity (coexistence of diabetes and obesity) and metabolic associated steatotic liver disease (MASLD) are two very frequent pathologies whose prevalence is increasing every day.

to find out how these two pathological entities are associated in a group of Spanish workers.

a descriptive, cross-sectional study was carried out in 219477 workers to assess the association between diabesity (applying a double criterion, the body mass index BMI and the Clínica Universitaria de Navarra body adiposity estimator CUN BAE) and different risk scales for MASLD and liver fibrosis.

all MASH and liver fibrosis risk scales show higher values in people with diabesity applying the two criteria compared to people without diabesity.

diabesity and MASLD and liver fibrosis risk scales show a significant association in our study.

Obesity has been identified as a crucial cause of non-communicable diseases, especially for healthcare workers who often take a brief lunch break with high energy and micro- and macronutrients deficient food.

Our study aims to investigate the clinical and economic effectiveness of the "Food Education Program" (FEP) among healthcare workers having weight problems. Four questionnaires were administered before and after FEP to explore the risk of psychological injury ("Psychological Injury Risk Indicator"), mental and general health status ("Goldberg's General Health Questionnaire-12" and "Short Form-36 health survey") and eating behavior ("Eating Attitudes Test"). The Return on Investment (ROI) was calculated on the base of absenteeism reduction in the 1-year period after FEP.

Fifty-one participants (78.4% females, mean age: 52.04 ± 8.94) were included in the study. They were mainly nurses (56.9%). 54.9% were obese and 43.1% overweight. The success rate was 32.1%; the reduction in BMI was more evident in the overweight participants than the obese subjects. A significant reduction of waist-to-hip ratio, glycosylated hemoglobin, total and LDL cholesterol, and an increase in vitamin D was observed (p-value: 0.047, 0.002, <0.001, 0.001, and 0.03). Scores on general health significantly improved (p-value <0.001 and 0.011). A mean per capita reduction of 3.70 days was observed in 1-year period after the intervention, with a ROI of 6.97.

Food Education Program represents a successful program to improve psychophysical wellbeing of healthcare workers through healthy nutritional plans, also having a notable positive impact on the organization, including its financial accounts.

Obesity is one of the biggest health problems in the 21st century and the leading health disorder amongst women of fertile age. Maternal obesity is associated with several adverse maternal and fetal outcomes. In this group of women, the risk for the development of hypertensive disorders of pregnancy (HDPs), such as gestational hypertension (GH) and pre-eclampsia (PE), is increased. In fact, there is a linear association between an increase in pre-pregnancy body mass index (BMI) and PE. Excessive weight gain during pregnancy is also related to the development of PE and GH. The role of obesity in the pathophysiology of HDP is complex and is most likely due to an interaction between several factors that cause a state of poor maternal cardiometabolic health. Adipokines seem to have a central role in HDP development, especially for PE. Hypoadiponectinemia, hyperleptinemia, insulin resistance (IR), and a proinflammatory state are metabolic disturbances related to PE pathogenesis, contributing to its development by inducing a state of maternal endothelial dysfunction. Hypertriglyceridemia is suggested to also be a part of the disease mechanisms of HDP. Therefore, this review seeks to explore the scientific literature to assess the complications of maternal obesity and its association with the development of HDP.

Obesity is now recognized as a multifaceted chronic disease that is intricately linked to metabolic, biochemical, and psychosocial dysfunction. In this article, we review the epidemiology of obesity, current understanding of its physiopathology, and the recommended staging system used to approach it as a chronic disease, and we include an overview of its health implications.

The global prevalence of obesity and type 2 diabetes mellitus (T2D) has risen in parallel over recent decades. Most individuals diagnosed with T2D exhibit adiposopathy-related diabetes (ARD), a condition characterized by hyperglycemia accompanied by three core features: increased ectopic and visceral fat deposition, dysregulated adipokine secretion favoring a pro-inflammatory state, and insulin resistance. Despite advancements in precision medicine, international guidelines for T2D continue to prioritize individualized therapeutic approaches focused on glycemic control and complications, and many healthcare providers predominantly maintain a glucocentric strategy. This review advocates for an adipocentric treatment paradigm for most individuals with T2D, emphasizing the importance of prioritizing weight loss and visceral fat reduction as key drivers of therapeutic intensification. By combining lifestyle modifications with pharmacological agents that promote weight loss-including SGLT-2 inhibitors, GLP-1 receptor agonists, or dual GLP-1/GIP receptor agonists-and, when appropriate, metabolic surgery, this approach offers the potential for disease remission in patients with shorter disease duration. For others, it enables superior metabolic control compared to traditional glucose-centered strategies while simultaneously delivering cardiovascular and renal benefits. In conclusion, an adipocentric treatment framework for ARD, which represents the majority of T2D cases, effectively integrates glucocentric and cardio-nephrocentric goals. This approach constitutes the optimal strategy for ARD due to its efficacy in achieving disease remission, improving metabolic control, addressing obesity-related comorbidities, and reducing cardiovascular and renal morbidity and mortality.

To determine if the positive outcomes from clinical trials regarding the safety and efficacy of metabolic bariatric surgery are reproducible at a national level.

A longitudinal registry-based observation study with data collected from all persons undergoing metabolic bariatric surgery in Australia from 28 February 2012-31 December 2021 including data from 122,567 index patients who underwent 134,625 completed bariatric procedures.

Defined adverse outcomes at 90-days (unplanned readmission, intensive care admission and re-operation; death), annual change in weight (percent total body weight loss (TBWL)), diabetes treatment and need for re-operation.

79.0% of participants were female. Mean age on the day of surgery was 44.0 years (SD 11.8; range 12.9-87.9 years) and mean BMI 41.7 kg/m2 (SD 7.6). At 5-years participants who underwent one anastomosis gastric bypass had TBWL 34.88% (SD 8.67%), roux-en-Y gastric bypass 30.73 % (SD 9.47%); sleeve gastrectomy 26.5% (SD 10.5%) and adjustable gastric bands 17.6% (SD 12.1%). At 90-days 3.6% of procedures recorded a defined adverse event. 13,904 (13.6%) primary participants reported being treated for diabetes at baseline. No medication for diabetes was required by 71.6% (follow-up 58%) at 1-year and 61% (follow-up 22%) at 5-years. 13 904 (13.6%) primary participants reported being treated for diabetes at baseline. No medication for diabetes was required by 71.6% (follow-up 58%) at 1-year and 61% (follow-up 22%) at 5-years.

Metabolic bariatric surgery is safe and induces substantial weight loss with reduced need for diabetes medications in the real-world.

NCT03441451.

Physical exercise is crucial in type 2 diabetes management (T2D), and training in the aquatic environment seems to be a promising alternative due to its physical properties and metabolic, functional, cardiovascular, and neuromuscular benefits. Research on combined training in aquatic and dry-land training environments is scarce, especially in long-term interventions. Thus, this study aims to investigate the effects of combined training in both environments on health outcomes related to the management of T2D patients.

This is a randomized, unicentric, single-blinded, comparator clinical trial with two parallel arms. Participants with T2D, of both sexes, aged at 45 to 80 years old, will be randomized into two groups (aquatic combined training (AQUA) and dry-land combined training (LAND)), both performing combined aerobic and resistance training three times a week on alternate days for 24 weeks. Aerobic training will be performed using continuous and pyramidal methods, with linear exercise intensity and duration progression. Intensity will be prescribed by rated effort perception (Borg scale 6 to 20). Resistance training will be performed using exercise for the trunk, upper and lower limbs maximum speed, and target repetition zone in aquatic and dry-land environments, respectively, using multiple sets in a linear dosage progression. Before, at 12 weeks, and after the 24 weeks of training, biochemical analyses, functional capacity, maximum muscle strength, body composition assessments, cardiovascular measures, and the administration of questionnaires to assess mental, cognitive, sleep quality, and quality of life will be conducted. Throughout the 24 weeks, the training load date and acute capillary glucose and blood pressure measurements will also be conducted. The data will be analyzed using the SPSS (29.0) statistical package, using a significance level of 0.05. For intra- and inter-group comparisons, generalized estimating equations will be applied and analyzed by intention-to-treat and per-protocol adopting the Bonferroni post hoc test.

The obtained results may provide insights to enhance understanding of the benefits of the aquatic and dry-land environment on various health outcomes, as well as acute aspects and safety considerations of the training. Moreover, this could support the development of intervention strategies to optimize the T2D management.

Brazilian Clinical Trial Registry (ReBEC) RBR-10fwqmfy. Registered on April 16, 2024.

Nonpharmacologic interventions (NPIs) constitute an important part of treatment for older adults, cover a broad and diverse range of interventions, and have advantages over pharmacologic interventions (eg, limited adverse side effects). However, an unambiguous definition of NPIs is still lacking. Defining NPIs may facilitate research on this topic and enhance comparability of results between studies, and might help to face the challenges of recognition, acceptation, funding, and implementation. Therefore, the aim of this review was to provide an overview and comparison of the definitions of NPIs used in the current literature on older adults.

A systematic review was performed to provide an overview of the definitions of NPIs that are used in the current literature on older populations and to organize the characteristics involved in the definitions.

People ≥60 years of age were included, not limited to a specific setting.

A systematic search was performed in the following 5 databases: PubMed, Embase, Clarivate Analytics/Web of Science Core Collection, Cumulative Index to Nursing and Allied Health Literature, and Wiley/Cochrane Library. The time frame within the databases was from inception to December 4, 2023. Review articles, editorials and consensus papers were included.

We included 28 articles. We organized the definitions of NPI according to 4 different aspects: types of interventions involved, target population, goals the interventions addressed, and requirements of the interventions. Definitions in the current literature can generally be divided into 2 groups: NPIs described as not involving medication, and more elaborated multidomain definitions. Based on the results, we formulated criteria for types of interventions that can be considered an NPI.

Using current descriptions and characteristics, elements for a new definition for NPIs were proposed. To improve research in this field, consensus needs to be reached regarding elements covered by a definition of NPIs.

Background: Diabetes has become one of the most challenging public health problems due to the alarming increase in prevalence and the morbidity and mortality attributed to its acute and chronic complications. Objective: This study aimed to investigate the development of chronic microvascular complications in sulfonylureas-treated diabetic patients and their correlations with glycemic control, risk factors and duration of the disease. Methods: This study included 200 patients that presented to "Providența" Medical Center, Iași. The information was obtained in a retrospective manner based on the observation sheets of the patients. A database was created, analyzed and statistically processed using the Microsoft Excel software (Version 15) and the chi-square test of independence. Results: The prevalence of diabetic polyneuropathy was 33.5%, while diabetic retinopathy was found in 27% of cases. For diabetic polyneuropathy, the results of the statistical analysis demonstrated a statistically significant dependence of the risk factors hyperlipidemia (significance level = 0.01) and overweight/obesity (significance level = 0.05). For diabetic retinopathy, the results demonstrated a statistically significant dependence of the risk factors hypertension (significance level = 0.05) and hyperlipidemia (significance level = 0.01). Conclusions: The present study reveals a strong correlation between the presence of risk factors and the development of microvascular complications of diabetes.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and diabesity (diabetes related to obesity) are interrelated since glucose and lipid alterations play a vital role in the development of both disorders. Due to their multi-variant metabolic features, more than one drug or natural product may be required to achieve proper therapeutic effects. This study aimed to evaluate the effectiveness of a formulation containing co-micronized palmitoylethanolamide and rutin (PEA-Rut) associated with hydroxytyrosol (HT), namely NORM3, against hepatic damage and metabolic alterations in high-fat diet (HFD)-induced diabesity in mice. NORM3 decreased the body weight and fat mass of obese mice. The formulation improved HFD-altered insulin sensitivity and hepatic glucose production and metabolism, as shown by glucose, insulin, pyruvate tolerance tests, Western blot, and real-time PCR. In the liver, NORM3 limited macro- and micro-vacuolar steatosis, as revealed by morphological analysis, and reduced the associated hepatic inflammation. NORM3 counteracted lipid dysfunctions of HFD animals, activating AMPK, a key cellular energy sensor, and normalizing the expression of carnitine palmitoyl-transferase (CPT)1, a rate-limiting enzyme of fatty acid β-oxidation, and other genes involved in lipid homeostasis. Relevantly, the hepatic antioxidant activity of NORM3 was proved (reduced ROS and increased detoxifying factors and enzymes). Finally, in vitro synergistic protective effects of the components (PEA-Rut and HT) on H2O2-induced oxidative challenge in HepG2 were determined (ROS production, inflammation, and antioxidant defense). Our results show the beneficial effect of NORM3 and its potential as an innovative phytotherapeutic combination in limiting hepatic damage progression and counteracting glucose and lipid dysmetabolism associated with diabesity.

This study investigated the protective effect of dapagliflozin on H9c2 cardiomyocyte function under high glucose and hypoxia/reoxygenation (HG-H/R) conditions and identified the underlying molecular mechanisms. Dapagliflozin reduced the level of lactate dehydrogenase and reactive oxygen species in cardiomyocytes under HG-H/R conditions and was accompanied by a decrease in caspase-3/9 activity. In addition, Dapagliflozin significantly reduced mitochondrial permeability transition pore opening and increased ATP content, accompanied by upregulation of OPA1 with autophagy-related protein molecules and activation of the AMPK/mTOR signalling pathway in HG-H/R treated cardiomyocytes. OPA1 knockdown or compound C treatment attenuated the protective effects of dapagliflozin on the cardiomyocytes under HG-H/R conditions. Downregulation of OPA1 expression increased mitochondrial intolerance in cardiomyocytes during HG-H/R injury and the AMPK-mTOR-autophagy signalling is a key mechanism for protecting mitochondrial function and reducing cardiomyocyte apoptosis. Collectively, dapagliflozin exerted protective effects on the cardiomyocytes under HG-H/R conditions. Dapagliflozin attenuated myocardial HG-H/R injury by activating AMPK/mTOR-OPA1-mediated mitochondrial autophagy.

Diabetes mellitus (DM) affects 537 million people as of 2021, and is projected to rise to 783 million by 2045. This positions DM as the ninth leading cause of death globally. Among DM patients, cardiovascular disease (CVD) is the primary cause of morbidity and mortality. Notably, the prevalence rates of CVD is alarmingly high among diabetic individuals, particularly in North America and the Caribbean (46.0%), and Southeast Asia (42.5%). The predominant form of CVD among diabetic patients is coronary artery disease (CAD), accounting for 29.4% of cases. The pathophysiology of DM is complex, involving insulin resistance, β-cell dysfunction, and associated cardiovascular complications including diabetic cardiomyopathy (DCM) and cardiovascular autonomic neuropathy (CAN). These conditions exacerbate CVD risks underscoring the importance of managing key risk factors including hypertension, dyslipidemia, obesity, and genetic predisposition. Understanding the genetic networks and molecular processes that link diabetes and cardiovascular disease can lead to new diagnostics and therapeutic interventions. Imeglimin, a novel mitochondrial bioenergetic enhancer, represents a promising medication for diabetes with the potential to address both insulin resistance and secretion difficulties. Effective diabetes management through oral hypoglycemic agents (OHAs) can protect the cardiovascular system. Additionally, certain antihypertensive medications can significantly reduce the risk of diabetes-related CVD. Additionally, lifestyle changes, including diet and exercise are vital in managing diabesity and reducing CVD risks. These interventions, along with emerging therapeutic agents and ongoing clinical trials, offer hope for improved patient outcomes and long-term DM remission. This study highlights the urgent need for management strategies to address the overlapping epidemics of DM and CVD. By elucidating the underlying mechanisms and risk factors, this study aims to guide future perspectives and enhance understanding of the pathogenesis of CVD complications in patients with DM, thereby guiding more effective treatment strategies.

Bariatric interventions have shown the best therapeutic benefits in individuals with obesity. They can be classified into surgical procedures (bariatric/metabolic surgery) and endoscopic procedures. Common surgical procedures include sleeve gastrectomy, Roux-en-Y gastric bypass, bilio-pancreatic diversion with or without duodenal switch and Stomach Intestinal Pylorus Sparing Surgery. Endoscopic procedures include intragastric balloons, transpyloric shuttle, endoscopic gastroplasties, aspiration therapy, duodenal mucosal resurfacing, duodeno-jejunal bypass liner, gastro-duodeno-jejunal bypass and incisionless magnetic anastomosis system among others. However, these procedures are limited by lack of wide availability, high costs, immediate and long-term complications and poor acceptability in some regions. Weight re-gain is a common concern and revisional metabolic surgery is often required. Appropriate pre-operative evaluation and correction of nutritional deficiencies post-surgery are very important. The most appropriate procedure for a person would depend on multiple factors like the intended magnitude of weight-loss, comorbidities and surgical fitness, as well as choice of the patient. Recently, glucagon-like insulinotropic peptide-1 receptor agonists (GLP) and the GLP-1/gastric inhibitory polypeptide co-agonist-Tirzepatide have shown remarkable weight loss potential, which is at par with bariatric interventions in some patients. How far these can help in avoiding invasive bariatric procedures in near future remains to be explored. An updated and comprehensive clinical review by He et al in the recent issue of World Journal of Diabetes address has addressed the avenues and challenges of currently available bariatric surgeries which will enable clinicians to make better decisions in their practice, including their applicability in special populations like the elderly and pediatric age groups, type 1 diabetes mellitus, and non-diabetics.

Overweight and obesity are conditions associated with serious comorbidities, such as diabetes and cardiovascular disease. Prevalence of excessive fat accumulation is increasing worldwide, and thus the need for efficient and sustainable weight loss regimes has become a major issue in clinical practice. Despite the important advances in the development of anti-obesity medications (AOM), their side effects, cost, and accessibility, are limiting factors for their routine use. Conversely, the studies of medicinal plants for weight management holds strong promise as a growing area of research. This review consolidates the representative evidence about the beneficial impacts of Morus alba on weight management and associated metabolic parameters, encompassing: inhibition of digestive enzymes, and thus contribution to the energy deficit required for weight loss, improvements in glucose and lipid metabolism, and attenuation of adiposity. Findings from in vitro, in vivo, and clinical investigations reviewed in the paper, demonstrate that white mulberry extracts have the potency to supplement efficiently and safely a healthy weight management approach.

Roux-en-Y gastric bypass (RYGB) has demonstrated excellent glycemic control and type 2 diabetes mellitus (T2DM) remission for patients with obesity and T2DM. Duration of T2DM is a consistent negative predictor of remission after RYGB. However, the exact timing to offer surgical intervention during the course of the disease is not well elucidated.

The authors performed a retrospective cohort study between 2008 and 2020 to establish the exact association between duration of T2DM and remission after RYGB. The authors divided our cohort into quartiles of preoperative disease duration to quantify the change in remission rates for each year of delay between T2DM diagnosis and RYGB. The authors also compared the average time to remission and changes in glycemic control parameters.

A total of 519 patients (67.2% female; age 53.4±10.7 year; BMI 46.6±8.4 kg/m 2 ) with a follow-up period of 6.6±3.8 years were included. Remission was demonstrated in 51% of patients. Longer duration of T2DM was a significant negative predictor of remission with an estimated decrease in remission rates of 7% for each year of delay [(OR=0.931 (95% CI: 0.892-0.971); P< 0.001)]. Compared to patients with <3 years of T2DM, remission decreased by 37% for patients with 3-6 years, 64% for those with 7-12 years, and 81% for patients with more than 12 years ( P <0.001). Half of the patients reached T2DM remission after 0.5 and 1.1 years, respectively, for the first and second quartiles, while patients in the other quartiles never reached 50% remission. Lastly, The authors noted an overall improvement in all glycemic control parameters for all quartiles at last follow-up.

Patients with a recent history of T2DM who undergo early RYGB experience significantly higher and earlier T2DM remission compared to patients with a prolonged history of preoperative T2DM, suggesting potential benefit of early surgical intervention to manage patients with obesity and T2DM.

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.

To study the real-world benefits and side effects of using semaglutide to manage patients with diabesity.

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.

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.

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.

Investigations involving high-intensity interval training (HIIT) have proven to be efficient in controlling diabesity. This study aimed to assess the impact of discontinuing HIIT and retraining within the context of diabesity. 75 C57BL6 mice went through 5 stages: baseline, induction of diabesity with Western diet, training, detraining, and retraining (6 weeks each period). Detraining led to elevated adiposity, exacerbated metabolic parameters and intestinal health, and altered gut microbiota composition. Retraining restored blood glucose regulation and enhanced intestinal health yet did not induce fat reduction. While both training and retraining exerted an effect on the composition of the gut microbiota, the impact of diet demonstrates a more substantial potency compared to that of exercise concerning intestinal health and microbiome. These findings may contribute to a broader understanding of diabesity management and introduce perspectives for the use of specific physical training to enhance patient outcomes and intestine health.

Insulin resistance (IR) is a global health challenge, often initiated by dysfunctional adipose tissue. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may have different effects on IR, but the mechanisms are unknown. This study aims to evaluate the protective effect of EPA and DHA against IR in a high-fat diet (HFD) mice model and investigate whether EPA and DHA alter IR modulate the G-protein-poupled receptor 120/peroxisome proliferator-activated receptor γ (GPR120/PPARγ) pathway in macrophages and adipocytes, which may affect IR in adipocytes. The findings of this study show that 4% DHA had a better effect in improving IR and reducing inflammatory cytokines in adipose tissue of mice. Additionally, in the cell experiment, the use of AH7614 (a GPR120 antagonist) inhibited the glucose consumption increase and the increasable expression of PPARγ and insulin signaling molecules mediated by DHA in adipocytes. Furthermore, GW9662 (a PPARγ antagonist) hindered the upregulation of glucose consumption and insulin signaling molecule expression induced by EPA and DHA in adipocytes. DHA exhibited significant effects in reducing the number of migrated cells and inflammation. The compounds AH7614 and GW9662 hindered the suppressive effects of EPA and DHA on macrophage-induced IR in adipocytes. These findings suggest that DHA has a stronger potential in improving IR in adipocytes through the GPR120/PPARγ pathway in macrophages, when compared to EPA.

To compare the acute effects of aquatic walking/running versus dry-land walking/running on blood glucose and plasma renin activity (PRA) in individuals with type 2 diabetes, participants with type 2 diabetes performed deep-water or dry-land walking and/or running sessions in a swimming pool or on an athletics track, respectively. Both sessions comprised seven blocks of 3 min at 85-90% of the heart rate deflection point (HRDP), interspersed with 2 min at <85% HRDP, totaling 35 min, with a 48 h interval between sessions. PRA and blood glucose were assessed before and immediately after the sessions. Generalized estimation equations were used to verify the session effects, with the Bonferroni post hoc test, considering the significance level as 0.05. Twelve individuals (53.2 ± 8.9 years) diagnosed with type 2 diabetes for 6.3 ± 6.34 years participated in the study. A reduction in PRA was found only after the aquatic session (-7.75 ng/mL/h; -69%; p: 0.034), while both aquatic and dry-land sessions similarly reduced the blood glucose levels (aquatic: -38 mg/dL, -21%; dry-land: -26 mg/dL, -14%; time effect, p = 0.007). Despite yielding similar glycemic reductions as dry-land walking/running, aquatic walking/running led to an expressive decrease in PRA among individuals with type 2 diabetes.

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.

To investigate the joint associations of diabetes and obesity with all-cause and cardiovascular disease (CVD) mortality in the Mexico City Prospective Study.

In total, 154 128 participants (67.2% women) were included in this prospective analysis. Diabetes was self-reported, while body mass index was used to calculate obesity. Using diabetes and obesity classifications, six groups were created: (a) normal (no diabetes and normal weight); (b) normal weight and diabetes; (c) overweight but not diabetes (overweight); (d) overweight and diabetes (prediabesity); (e) obesity but not diabetes (obesity); and (f) obesity and diabetes (diabesity). Associations between these categories and outcomes were investigated using Cox proportional hazard models adjusted for confounder factors.

During 18.3 years of follow-up, 27 197 (17.6%) participants died (28.5% because of CV causes). In the maximally adjusted model, participants those with the highest risk {hazard ratio (HR): 2.37 [95% confidence interval (CI): 2.24-2.51]}, followed by those with diabesity [HR: 2.04 (95% CI: 1.94-2.15)]. Similar trends of associations were observed for CVD mortality. The highest CV mortality risk was observed in individuals with diabesity [HR: 1.80 (95% CI: 1.63-1.99)], followed by normal weight and diabetic individuals [HR: 1.78 (95% CI: 1.60-1.98)].

This large prospective study identified that diabetes was the main driver of all-cause and CVD mortality in all the categories studied, with diabesity being the riskiest. Given the high prevalence of both conditions in Mexico, our results reinforce the importance of initiating prevention strategies from an early age.

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.

Heparin-induced thrombocytopenia can occur in obese subjects. The medical comorbidities associated with obesity may contribute to the pathogenesis of this disease. It is unknown, however, which specific medical comorbidities and if higher odds of thrombosis are present in obese heparin-induced thrombocytopenia patients. We sought to determine whether obese heparin-induced thrombocytopenia subjects had higher odds of both comorbidities and thrombosis, hypothesizing that this patient population would have higher odds of both these conditions.

This was a multi-center retrospective study utilizing TriNetX©, an electronic health record database, in subjects aged 18-99 years diagnosed with heparin-induced thrombocytopenia. The cohort was divided into two groups (1) non-obese (body mass index < 30 kg/m2) and (2) obese (body mass index ⩾ 30 kg/m2). We evaluated patient characteristics, diagnostic, laboratory, medication, and procedure codes.

A total of 1583 subjects (696 (44.0%) non-obese and 887 (56.0%) obese) were included. Obese subjects had higher odds of diabetes with complications (OR = 1.73, 95% CI = 1.35-2.22, p < 0.001) and without complications (OR = 1.81, 95% CI = 1.47-2.22, p < 0.001). This association was still present after correcting for demographic and clinical factors. There were no increased odds of thrombosis observed in the obesity group.

Our study found that obese heparin-induced thrombocytopenia subjects had higher odds of having a diabetes mellitus comorbidity, but did not have higher odds of thrombosis. Given obesity is considered a hypercoagulable state, further study may be needed to understand why obese subjects diagnosed with heparin-induced thrombocytopenia do not have higher rates of thrombosis.

The treatment of obesity and its comorbidities ranges from clinical management involving lifestyle changes and medications to bariat-ric and metabolic surgery. Various endoscopic bariatric and metabolic therapies recently emerged to address an important therapeutic gap by offering a less invasive alternative to surgery that is more effective than conservative therapies. This article compre-hensively reviews the technical aspects, mechanism of action, outcomes, and future perspectives of one of the most promising endoscopic bariatric and metabolic therapies, named duodenojejunal bypass liner. The duodenojejunal bypass liner mimics the mechanism of Roux-en-Y gastric bypass by preventing food contact with the duodenum and proximal jejunum, thereby initiating a series of hormonal changes that lead to delayed gastric emptying and malabsorptive effects. These physiological changes result in significant weight loss and improved metabolic control, leading to better glycemic levels, preventing dyslipidemia and non-alcoholic fatty liver disease, and mitigating cardiovascular risk. However, concern ex-ists regarding the safety profile of this device due to the reported high rates of severe adverse events, particularly liver abscesses. Ongo-ing technical changes aiming to reduce adverse events are being evaluated in clinical trials and may provide more reliable data to sup-port its routine use in clinical practice.

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.

To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.

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.

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.

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.

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 β-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.

In 2021, the International Diabetes Federation (IDF) reported that the prevalence of diabetes in Pakistan was 9.6%, higher than the global average. However, adherence to treatment guidelines, e.g., American Diabetes Association and Pakistan Endocrine Society and prescription patterns for Oral anti-diabetes (OAD), is poorly understood in Pakistan. Therefore, this study aimed to examine the prescribing practices of anti-diabetic medications, an association of lifestyle modification with drugs prescribed, and their effectiveness in preserving ideal glycemic levels in diabetic patients undergoing treatment in tertiary care teaching hospitals in rural and urban Pakistan. In this cross-sectional study, data were collected from prescriptions of outpatient diabetic patients from different rural and urban tertiary care hospitals between October 2021 and February 2022. 388 participants were enrolled in the study for a detailed interview on prescription evaluation and glycemic control. The coinvestigators conducted an interview with the patient and used a pre-validated questionnaire to collect the data. The relationship between following treatment guidelines and clinical and demographic factors was found using chi-square tests for bivariate analyses. The study reported that out of 388, the mean ages of the patients were 48 ± 12.4, and the majority were female. It was observed that 60.1% and 66.5% have uncontrolled fasting and random blood glucose, respectively. The education level of the study participants was also below par to have a complete understanding of the medical condition and self-management therapy. Even though they were taking the right medications-an average prescription regimen included 5.08 medications-52.1% of the studied people had glycated haemoglobin (HbA1c) levels higher than the therapeutic threshold set by the International Diabetes Federation. In this modern era, it was observed that the prescribing trend was still focused on traditional therapeutic options Biguanides, sulfonylureas, and dipeptidyl peptidase-4 inhibitors were prescribed in 64.6% of the patients. A significant association was found between glycemic control and body mass index, adherence to lifestyle modifications, and the number of medications prescribed (p-value < 0.05). The study reveals that Pakistan's prescribing practices do not align with international and national guidelines, leading to a high prevalence of uncontrolled diabetes and widespread use of polypharmacy among patients. To address this issue, policymakers should prioritize establishing a comprehensive national diabetes action plan. Additionally, there is a pressing need to develop diabetes education and awareness programs emphasizing the importance of lifestyle modifications for effective diabetes management.

Diabesity, the intersection of obesity and diabetes, presents a global health crisis with profound implications. Addressing diabesity requires multifaceted strategies, with diet playing a pivotal role. Over the last 15 years, clinical studies have intensified their exploration of various dietary approaches in diabesity management. This literature review aims to synthesize findings from clinical studies conducted in the last 15 years, shedding light on the efficacy, mechanisms, and nuances of different diet types in diabesity management with special focus on the Mediterranean diet (MD).

Thorough research of academic databases yielded a collection of relevant clinical studies. These studies encompassed a range of dietary strategies, including the MD, low-carbohydrate diets, plant-based diets, high-protein diets, low-fat regimens, and intermittent fasting. Key findings, methodologies, and outcomes were thoroughly extracted and analyzed.

The last 15 years have witnessed considerable improvements in recognizing the role of human nutritional habits in diabesity management. The MD appears to be the most well-recognized diet, exerting favorable effects against both obesity and diabetes. Low-carbohydrate diets were found to enhance glycemic regulation and decrease insulin resistance. Plant-based diets demonstrated potential benefits in weight management and cardiometabolic health. High-protein, low-fat dietary models exhibited positive effects on satiety and body weight decline. Intermittent fasting regimens also exerted metabolic improvements and body weight decline. Personalization emerged as a crucial factor in dietary recommendations.

Clinical studies from the last 15 years underscore the intricate relationship between diet types and diabesity management. The above results contribute to an increasing body of evidence, emphasizing the need for tailored dietary approaches and especially the MD. Healthcare providers can utilize this knowledge to offer personalized dietary recommendations for individuals with diabesity, potentially curbing the rise of these twin epidemics and improving the well-being of affected populations.

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.

It is widely accepted that pancreatic islet β-cell failure and the onset of type 2 diabetes (T2DM) constitute an intricate interplay between the genetic expression of the disease and a host of intracellular events including increased metabolic (oxidative, endoplasmic reticulum) stress under the duress of glucolipotoxicity. Emerging evidence implicates unique roles for Caspase Recruitment Domain containing protein 9 (CARD9) in the onset of metabolic diseases, including obesity and insulin resistance. Mechanistically, CARD9 has been implicated in the regulation of p38MAPK and NFkB signaling pathways culminating in cellular dysfunction. Several regulatory factors, including B-cell lymphoma/leukemia 10 (BCL10) have been identified as modulators of CARD9 function in multiple cell types. Despite this evidence on regulatory roles of CARD9-BCL10 signalome in the onset of various pathological states, putative roles of this signaling module in islet β-cell dysfunction in metabolic stress remain less understood. This brief review is aimed at highlighting roles for CARD9 in islet β-cell function under acute (physiological insulin secretion) and long-term (cell dysfunction) exposure to glucose. Emerging roles of other signaling proteins, such as Rac1, BCL10 and MALT1 as contributors to CARD9 signaling in the islet β-cells are also reviewed. Potential avenues for future research toward the development of novel therapeutics for the prevention CARD9-BCL10-Rac1 (CBR) signalome-induced β-cell defects under metabolic stress are discussed.