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Aim/objectives: This study aims to ascertain the prevalence and influencing factors of diabesity among adult patients visiting the General Outpatient clinic of three government healthcare facilities in Calabar, Nigeria. The objective is to enhance healthcare delivery to at-risk patients., Methods: A cross-sectional descriptive study design incorporating a mixed method approach, including quantitative and qualitative components such as Focused Group Discussions (FGD) and Key Informant Interviews (KII), was employed. The study population consisted of 190 participants aged 18 to 72 years with a body mass index (BMI) of ≥ 30kg/m2, selected using a systematic random sampling technique and analysed using SPSS and Atlas.ti., Results: Sociodemographic variables indicated that the highest number of respondents fell within the 35-44 years (37.3%), with 83.7% being female and 76.8% married. Furthermore, 65.8% were classified as having class 1 obesity, while only 38% self-identified as obese. The occurrence of diabesity was found to be 12.6% (i.e., BMI ≥30 vs. FBS ≥ 7.0), with 38% of cases being previously undiagnosed. Qualitative assessment through KIIs and FGDs revealed that unhealthy diets and lack of exercise were major contributing factors to diabesity., Conclusion: This study has disclosed a 12.6% occurrence of diabesity within the study population, with 38% of cases being previously undiagnosed. Unhealthy diets, snacking, and lack of exercise were identified as significant indicators of diabesity., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

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.

Background: 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)., Methods: 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., Results: 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., Conclusions: 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.

Aims: The purpose of this review is to explore the interconnected pathways of the microbiota-gut-brain axis (MGBA), focusing on the roles of the vagus nerve and glucagon like peptide-1 in appetite control, and in the development of obesity and diabetes., Methods: Type 2 diabetes mellitus (T2DM) and obesity are metabolic disorders whose prevalence has significantly increased in recent decades and is expected to increase every year, to pandemic proportions. These two pathologies often coexist and have substantial public health implications. The term "diabesity" defines the pathophysiological connection between overweight and T2DM. The gut microbiota affects many aspects of the host. Beyond the regulation of intestinal functions and the activation of immune responses, the gut microbiota plays a role in central nervous system functions (i.e., mood, and psychiatric conditions associated with stress and memory) and is a central regulator of metabolism and appetite., Results: The MGBA involves pathways such as the autonomic and enteric nervous systems, the hypothalamic- pituitary-adrenal axis, the immune system, enteroendocrine cells, and microbial metabolites. Notably, the vagus nerve plays an essential role in eating behavior by modulating appetite and learning nutritional preferences., Conclusions: Because of its enteroendocrine cell-mediated interaction with the gut microbiota, the vagus nerve may provide a potential pathway through which gut microorganisms influence host feeding behavior and metabolic control of physiological and pathological conditions., (© 2023. The Author(s).)

Introduction: To date, the 21 st Century has witnessed key developments in the management of diabesity (a conflation of obesity and Type 2 Diabetes Mellitus [T2D]), including Glucagon Like Peptide 1 (GLP1) receptor agonist therapies, and recently the 'designer' GLP1 Poly-agonist Peptides (GLP1PPs)., Areas Covered: A PubMed search of published data on the GLP1PP class of therapies was conducted. The gut-brain axis forms complex multi-directional interlinks that include autonomic nervous signaling, components of the gut microbiota (including metabolic by-products and gram-negative cell wall components [e.g. endotoxinaemia]), and incretin hormones that are secreted from the gut in response to the ingestion of nutrients. The development of dual-incretin agonist therapies includes combinations of the GLP1 peptide with Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon (Gcg), Cholecystokinin (CCK), Peptide YY (PYY), and Glucagon-Like Peptide 2 (GLP2). Triple incretin agonist therapies are also under development., Expert Opinion: At the dawn of a new era in the therapeutic management of diabesity, the designer GLP1PP class holds great promise, with each novel combination building on a preexisting palimpsest of clinical data and insights. Future innovations of the GLP1PP class will likely enable medically induced weight loss and glycemic control in diabesity to rival or even out-perform those resulting from bariatric surgery.

Obesity and type 2 diabetes (T2DM) are major public health concerns associated with serious morbidity and increased mortality. Both obesity and T2DM are strongly associated with adiposopathy, a term that describes the pathophysiological changes of the adipose tissue. In this review, we have highlighted adipose tissue dysfunction as a major factor in the etiology of these conditions since it promotes chronic inflammation, dysregulated glucose homeostasis, and impaired adipogenesis, leading to the accumulation of ectopic fat and insulin resistance. This dysfunctional state can be effectively ameliorated by the loss of at least 15% of body weight, that is correlated with better glycemic control, decreased likelihood of cardiometabolic disease, and an improvement in overall quality of life. Weight loss can be achieved through lifestyle modifications (healthy diet, regular physical activity) and pharmacotherapy. In this review, we summarized different effective management strategies to address weight loss, such as bariatric surgery and several classes of drugs, namely metformin, GLP-1 receptor agonists, amylin analogs, and SGLT2 inhibitors. These drugs act by targeting various mechanisms involved in the pathophysiology of obesity and T2DM, and they have been shown to induce significant weight loss and improve glycemic control in obese individuals with T2DM.

Background: Diabetes and obesity in adults are global issues. Obesity and type 2 diabetes mellitus (T2DM) are increasingly categorized under the umbrella term "diabesity." Health risk factors (HRFs), which include altering sleep habits and reducing sugar-sweetened beverages (SSBs) consumption, have emerged as relatively novel and crucial strategies for preventing and treating diabetes., Objective: We aimed to explore: 1) whether SSBs could affect diabesity in China's community; 2) whether HRFs could moderate this relationship; and 3) whether a three-way interaction exists between HRFs, SSBs, and diabesity., Methods: On December 10, 2018, we investigated diabetes complications in four cities in Anhui Province and obtained basic and lifestyle information using a detailed questionnaire. The primary exposure was SSBs and outcomes were body mass index (BMI) and waist circumference (WC), while glycated hemoglobin (HbA1c) and sleep patterns (including duration and disorders) were considered moderators., Results: Overall, 1920 participants were enrolled, and those who did not complete the questionnaire were excluded. Finally, this study included 1765 participants, with a response rate of 92.0%. The mean age was (57.10 ± 10.0) years. Patients with lower educational levels were more likely to have a lower prevalence of WC ( χ 2 = 2.73) and BMI ( χ 2 = 3.47), and some HRFs were positively correlated with WC and BMI. Additionally, SSBs were significantly associated with BMI (β = 1.29) and WC (β = 2.97), and there was also differences based on sex, some HRFs, such as HbA1c, FBG and TG, showed higher levels in male participants, whereas TC level was higher in female participants. In the moderation analysis, sleep patterns were also associated with total cholesterol, triglyceride, and BMI. Furthermore, there were three-way interaction effects among HbA1c, sleep patterns, and SSBs on total cholesterol, triglyceride, BMI, and WC. Moreover, sensitivity analysis demonstrated that our results were robust., Conclusion: SSBs positively correlated with patterns dose-dependently. Moreover, SSBs could also be associated with sleep patterns, and blood glucose levels were correlated with diabesity. A three-way interaction effect was discovered between SSBs, sleep patterns, blood glucose levels, and patterns. Therefore, understanding the diabesity caused by SSBs and other HRFs can help prevent its occurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Liu, Xu, Wang, Zhang, Jiang, Zhang and the China National Diabetic Chronic Complications Study Group.)

Cardiovascular disease (CVD) is the leading cause of death in the world. In 2019, 550 million people were suffering from CVD and 18 million of them died as a result. Most of them had associated risk factors such as high fasting glucose, which caused 134 million deaths, and obesity, which accounted for 5.02 million deaths. Diabesity, a combination of type 2 diabetes and obesity, contributes to cardiac, metabolic, inflammation and neurohumoral changes that determine cardiac dysfunction (diabesity-related cardiomyopathy). Epicardial adipose tissue (EAT) is distributed around the myocardium, promoting myocardial inflammation and fibrosis, and is associated with an increased risk of heart failure, particularly with preserved systolic function, atrial fibrillation and coronary atherosclerosis. In fact, several hypoglycaemic drugs have demonstrated a volume reduction of EAT and effects on its metabolic and inflammation profile. However, it is necessary to improve knowledge of the diabesity pathophysiologic mechanisms involved in the development and progression of cardiovascular diseases for comprehensive patient management including drugs to optimize glucometabolic control. This review presents the mechanisms of diabesity associated with cardiovascular disease and their therapeutic implications.

Obesity-associated diabetes mellitus, a chronic metabolic affliction accounting for 90% of all diabetic patients, has been affecting humanity extremely badly and escalating the risk of developing other serious disorders. It is observed that 0.4 billion people globally have diabetes, whose major cause is obesity. Currently, innumerable synthetic drugs like alogliptin and rosiglitazone are being used to get through diabetes, but they have certain complications, restrictions with severe side effects, and toxicity issues. Recently, the frequency of plant-derived phytochemicals as advantageous substitutes against diabesity is increasing progressively due to their unparalleled benefit of producing less side effects and toxicity. Of these phytochemicals, dietary polyphenols have been accepted as potent agents against the dual sword "diabesity". These polyphenols target certain genes and molecular pathways through dual mechanisms such as adiponectin upregulation, cannabinoid receptor antagonism, free fatty acid oxidation, ghrelin antagonism, glucocorticoid inhibition, sodium-glucose cotransporter inhibition, oxidative stress and inflammation inhibition etc. which sequentially help to combat both diabetes and obesity. In this review, we have summarized the most beneficial natural polyphenols along with their complex molecular pathways during diabesity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Type 2 diabetes with obesity is regarded as an incurable, progressive disease with many complications. The hypothesis was tested that glycated haemoglobin (HbA1c) and the insulin release curve can be restored by traceable systematic methods., Methods: 122 people with diabesity were investigated before and after three and 6 months of traceable systematic management methods. Basal body mass index (BMI), fatty liver, HbA1c, and insulin release curve were measured., Results: After 3 months of traceable systematic management, BMI decreased from 30.76 ± 0.48 to 21.86 ± 0.09 kg/m2 (p < 0.001) and remained stable during the last 3 months (21.82 ± 0.09 kg/m2 at 6 months). Colour Doppler ultrasound showed non-alcoholic fatty liver disease (NAFLD) in all diabesity participants at baseline. At 3 months, only one participant had low-grade fatty liver, and fatty liver was reversed in other participants (p < 0.001). The number and grade of fatty liver at 6 months were the same as at 3 months. Fasting plasma glucose decreased and continued to decrease thereafter (p < 0.001). Two-hour postprandial plasma glucose decreased and continued to decline until 6 months (p < 0.001). HbA1c also decreased and maintained this level at 6 months. At baseline, the peak value of insulin release was 1,141.09 ± 43.02 pmol/L at 2 h after meals, and the early phase of insulin secretion was lost. After 3 months of management, the insulin concentration was 621.62 ± 19.32 pmol/L at 2 h after meals. After 6 months, the value decreased, and the early phase of insulin secretion recovered., Conclusions: Normalization of the insulin release curve in type 2 diabetes was achieved by traceable systematic methods. This was associated with recovery from NAFLD. Diabesity is reversible by traceable systematic management., (© 2022 S. Karger AG, Basel.)

Background: Costs are important cause of therapeutic noncompliance in type-2 diabetes mellitus (T2DM). Half-tablet empagliflozin (EMPA)-25 mg has lowest monthly cost among all EMPA preparations; data is unavailable on efficacy of half EMPA-25. This study compared real world weight loss and glycaemic outcomes of 10 mg versus 12.5 mg versus 25 mg of EMPA., Methods: Data, retrospectively captured from records of 2 different centresfor patients > 35 years-age having T2DM on EMPA as part of standard pharmacotherapy for T2DM, having > 6 months follow-up data available was analysed. Patients were in 3-groups depending on EMPA dosage: Group 1 on EMPA 10 mg/day (1-tablet EMPA-10), Group-2 on EMPA 12.5 mg/day (half-tablet EMPA-25), and Group 3 on EMPA 25 mg/day (1-tablet EMPA-25). Primary endpoints were glycaemic efficacy and weight-loss., Results: Of 3601 records screened, data from 599 patients (184, 239 and 176 in Group-1, 2 and 3 respectively) was analysed. All 3 groups were comparable with regards to sex, blood pressure, haemoglobin, renal function, medications use. Group-3 were significantly older, had longest diabetes duration, highest HbA1c and lowest body mass index. Glycaemic efficacy was comparable among groups (ΔHbA1c Groups 1-3: -0.9 (-1.9 - 0.0), -1.0 (-1.8 - 0.5) and - 1.0 (-1.5 - 0.22], respectively; P = 0.363). Patients on EMPA 12.5 or 25 mg/d had significantly higher total (-1.4 [-3.0 -0.2] vs. -0.3 [-2.4 - 1.32] kg; P = 0.028) and percent weight-loss (-1.75% [-4.15 - 0.26] vs. -0.44% [-3.11 - 1.39]; P = 0.039), and significantly higherfraction achieving HbA1c < 5.7% (12% vs. 0; P = 0.021), compared to EMPA-10., Conclusion: Half EMPA-25 is the most cost effective way of using EMPA in clinical practice., Competing Interests: None

Introduction: Obesity is frequently a comorbidity of type 2 diabetes. Even modest weight loss can significantly improve glucose homeostasis and lessen cardiometabolic risk factors in patients with type 2 diabetes, but lifestyle-based weight loss strategies are not long-term effective. There is an increasing need to consider pharmacological approaches to assist weight loss in the so called diabesity syndrome. Aim of this review is to analyze the weight-loss effect of non-insulin glucose lowering drugs in patients with type 2 diabetes., Material and Methods: A systematic analysis of the literature on the effect of non-insulin glucose lowering drugs on weight loss in patients with type 2 diabetes was performed. For each class of drugs, the following parameters were analyzed: kilograms lost on average, effect on body mass index and body composition., Results: Our results suggested that anti-diabetic drugs can be stratified into 3 groups based on their efficacy in weight loss: metformin, acarbose, empagliflozin and exenatide resulted in a in a mild weight loss (less than 3.2% of initial weight); canagliflozin, ertugliflozin, dapagliflozin and dulaglutide induces a moderate weight loss (between 3.2% and 5%); liraglutide, semaglutide and tirzepatide resulted in a strong weight loss (greater than 5%)., Conclusions: This study shows that new anti-diabetic drugs, particularly GLP1-RA and Tirzepatide, are the most effective in inducing weight loss in patients with type 2 diabetes. Interestingly, exenatide appears to be the only GLP1-RA that induces a mild weight loss., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Obesity and type 2 diabetes mellitus have become a significant public health problem in the past decades. Their prevalence is increasing worldwide each year, greatly impacting the economic and personal aspects, mainly because they frequently coexist, where the term "diabesity" may be used. The drug class of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is one of the most modern therapy options in managing these metabolic disorders. This review focuses on the effects of liraglutide, a long-acting GLP-1 RA, in diabesity and non-diabetic excess weight. This drug class improves glycemic control by enhancing insulin secretion from the beta-pancreatic cells and inhibiting glucagon release. Furthermore, other effects include slowing gastric emptying, increasing postprandial satiety, and reducing the appetite and food consumption by influencing the central nervous system, with weight reduction effects. It also reduces cardiovascular events and has positive effects on blood pressure and lipid profile. A lower-dose liraglutide (1.2 or 1.8 mg/day) is used in patients with diabetes, while the higher dose (3.0 mg/day) is approved as an anti-obesity drug. In this review, we have summarized the role of liraglutide in clinical practice, highlighting its safety and efficacy as a glucose-lowering agent and a weight-reduction drug in patients with and without diabetes.

Aims: The relationship between iron status, obesity and type 2 diabetes mellitus (T2DM) has scarcely been tested. This study hypothesizes that patients with obesity and T2DM have altered iron metabolism., Methods: 537 T2DM patients were selected from the cross-sectional DICARIVA study excluding patients with high-sensitivity-C-reactive-protein (hs-CRP) ≥  10 mg/L. Three groups according to body mass index (BMI) and waist perimeter (WP) were analysed: a) BMI < 30 kg/m 2 , non-high WP (n = 105); b) BMI < 30 kg/m 2 , high WP (n = 202); and c) diabesity, BMI ≥  30 kg/m 2 , high WP (n = 230). Group differences on cardiometabolic and iron status markers were tested., Results: Women had significantly lower iron, ferritin, and transferrin saturation (TSAT) but higher transferrin and total iron binding capacity than men. Triglycerides/HDL-c ratio, as insulin-resistance (IR) marker, was higher in men while hs-CRP in women. TSAT was inversely related to BMI and hs-CRP. The diabesity group showed the highest hs-CRP (p < 0.001) and IR (p < 0.001) with the lowest TSAT (p = 0.003)., Conclusions: Low TSAT was highly prevalent in diabesity, mainly in women, suggesting that IR, inflammation, and abdominal adiposity alter iron transport and accumulation. The convenience of iron supplementation in diabesity patients with low TSAT should be urgently assessed, due the pro-oxidant effects of excess iron., (Copyright © 2021 Elsevier B.V. All rights reserved.)

(1) Aims: Diabesity, defined as diabetes occurring in the context of obesity, is a serious health problem that is associated with an increased risk of premature heart attack, stroke, and death. To date, a key challenge has been to understand the molecular pathways that play significant roles in diabesity. In this study, we aimed to investigate the genetic links between diabetes and obesity in diabetic individuals and highlight the role(s) of shared genes in individuals with diabesity. (2) Methods: The interactions between the genes were analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) tool after the compilation of obesity genes associated with type 1 diabetes (T1D), type 2 diabetes (T2D), and maturity-onset diabetes of the young (MODY). Cytoscape plugins were utilized for enrichment analysis. (3) Results: We identified 546 obesity genes that are associated with T1D, T2D, and MODY. The network backbone of the identified genes comprised 514 nodes and 4126 edges with an estimated clustering coefficient of 0.242. The Molecular Complex Detection (MCODE) generated three clusters with a score of 33.61, 16.788, and 6.783, each. The highest-scoring nodes of the clusters were AGT , FGB , and LDLR genes. The genes from cluster 1 were enriched in FOXO-mediated transcription of oxidative stress, renin secretion, and regulation of lipolysis in adipocytes. The cluster 2 genes enriched in Src homology 2 domain-containing (SHC)-related events triggered by IGF1R , regulation of lipolysis in adipocytes, and GRB2: SOS produce a link to mitogen-activated protein kinase (MAPK) signaling for integrins. The cluster 3 genes ere enriched in IGF1R signaling cascade and insulin signaling pathway. (4) Conclusion: This study presents a platform to discover potential targets for diabesity treatment and helps in understanding the molecular mechanism.

Obesity is a condition of rising prevalence worldwide, with important socioeconomic implications, being considered as a growing public health concern. Frequently, obesity brings other complications in addition to itself-like Type 2 Diabetes Mellitus (T2DM)-sharing origin, risk factors and pathophysiological mechanisms. In this context, some authors have decided to include both conditions as a unique entity known as "diabesity". In fact, understanding diabesity as a single disease is possible to maximise the benefits from therapies received in these patients. Gut microbiota plays a key role in individual's health, and their alterations, either in its composition or derived products are related to a wide range of metabolic disorders like T2DM and obesity. The present work aims to collect the different changes reported in gut microbiota in patients with T2DM associated with obesity and their possible role in the onset, development, and establishment of the disease. Moreover, current research lines to modulate gut microbiota and the potential clinical translation derived from the knowledge of this system will also be reviewed, which may provide support for a better clinical management of such a complex condition.

Background: The endoscopically implanted duodenal-jejunal bypass liner (DJBL) is an attractive alternative to bariatric surgery for obese diabetic patients. This article aims to study dynamical aspects of the glycaemic profile that may influence DJBL effects., Methods: Thirty patients underwent DJBL implantation and were followed for 10 months. Continuous glucose monitoring (CGM) was performed before implantation and at month 10. Dynamical variables from CGM were measured: coefficient of variation of glycaemia, mean amplitude of glycaemic excursions (MAGE), detrended fluctuation analysis (DFA), % of time with glycaemia under 6.1 mmol/L (TU6.1), area over 7.8 mmol/L (AO7.8) and time in range. We analysed the correlation between changes in both anthropometric (body mass index, BMI and waist circumference) and metabolic (fasting blood glucose, FBG and HbA1c) variables and dynamical CGM-derived metrics and searched for variables in the basal CGM that could predict successful outcomes., Results: There was a poor correlation between anthropometric and metabolic outcomes. There was a strong correlation between anthropometric changes and changes in glycaemic tonic control (∆BMI-∆TU6.1: rho = - 0.67, P < .01) and between metabolic outcomes and glycaemic phasic control (∆FBG-∆AO7.8: r = .60, P < .01). Basal AO7.8 was a powerful predictor of successful metabolic outcome (0.85 in patients with AO7.8 above the median vs 0.31 in patients with AO7.8 below the median: Chi-squared = 5.67, P = .02)., Conclusions: In our population, anthropometric outcomes of DJBL correlate with improvement in tonic control of glycaemia, while metabolic outcomes correlate preferentially with improvement in phasic control. Assessment of basal phasic control may help in candidate profiling for DJBL implantation., (© 2020 John Wiley & Sons Ltd.)

Diabesity is the combination of type 2 diabetes and obesity characterized by chronic low-grade inflammation. The Wnt signaling act as an evolutionary pathway playing crucial role in regulating cellular homeostasis and energy balance from hypothalamus to metabolic organs. Aberrant activity of certain appendages in the canonical and non-canonical Wnt system deregulates metabolism and leads to adipose tissue expansion, this key event initiates metabolic stress causing metaflammation and obesity. Metaflammation induced obesity initiates abnormal development of adipocytes mediating through the non-canonical Wnt signaling inhibition of canonical Wnt pathway to fan the flames of adipogenesis. Moreover, activation of toll like receptor (TLR)-4 signaling in metabolic stress invites immune cells to release pro-inflammatory cytokines for recruitment of macrophages in adipose tissues, further causes polarization of macrophages into M1(classically activated) and M2 (alternatively activated) subtypes. These events end with chronic low-grade inflammation which interferes with insulin signaling in metabolic tissues to develop type 2 diabetes. However, there is a dearth in understanding the exact mechanism of Wnt-TLR axis during diabesity. This review dissects the molecular facets of Wnt and TLRs that modulates cellular components during diabesity and provides current progress, challenges and alternative therapeutic strategies at preclinical and clinical level., Competing Interests: Declaration of Competing Interest Authors declared no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Diabesity is an abnormal metabolic condition shown by patients with obesity that develop type 2 diabetes mellitus. Patients with diabesity present with insulin resistance, reduced vascular response to insulin, and vascular endothelial dysfunction. Along with the several well-described mechanisms of insulin resistance, a state of endoplasmic reticulum (ER) stress, where the primary human targets are the adipose tissue, liver, skeletal muscle, and the foetoplacental vasculature, is apparent. ER stress characterises by the activation of the unfolded protein response via three canonical ER stress sensors, i.e., the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6. Slightly different cell signalling mechanisms preferentially enable in diabesity in the ER stress-associated insulin resistance for adipose tissue (IRE1α/X-box binding protein 1 mRNA splicing/c-jun N-terminal kinase 1 activation), skeletal muscle (tribbles-like protein 3 (TRB3)/proinflammatory cytokines activation), and liver (PERK/activating transcription factor 4/TRB3 activation). There is no information in human subjects with diabesity in the foetoplacental vasculature. However, the available literature shows that pregnant women with pre-pregnancy obesity or overweight that develop gestational diabetes mellitus (GDM) and their newborn show insulin resistance. ER stress is recently reported to be triggered in endothelial cells from the human umbilical vein from mothers with pre-pregnancy obesity. However, whether a different metabolic alteration to obesity in pregnancy or GDM is present in women with pre-pregnancy obesity that develop GDM, is unknown. In this review, we summarised the findings on diabesity-associated mechanisms of insulin resistance with emphasis in the primary targets adipose, skeletal muscle, liver, and foetoplacental tissues. We also give evidence on the possibility of a new GDM-associated metabolic condition triggered in pregnancy by maternal obesity, i.e. gestational diabesity, leading to ER stress-associated insulin resistance in the human foetoplacental vasculature., (Copyright © 2018. Published by Elsevier Ltd.)

The prevalence of "diabesity" - diabetes related to obesity - has increased tremendously over the past few decades because of the global obesity epidemic. Although bariatric surgery is the best treatment option for patients with diabesity, a majority of patients are managed only with antidiabetic drugs for various reasons. Diabetes control with antidiabetic agents may affect diabesity outcomes positively or negatively because of their effects on body weight and other metabolic parameters. For this reason, rational use of anti-diabetic medications is imperative to optimise long-term management of diabesity. Understanding the molecular mechanisms of antidiabetic drugs and/or drug combinations on diabesity outcomes are therefore important not only for the basic scientists but also for clinicians. This review explores the molecular signalling cascades of antidiabetic medications in the management of diabesity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Obesity and type 2 diabetes mellitus (T2DM) are diseases associated with hypertension and metabolic alterations. A significant group of patients present both obesity and T2DM, a condition defined as diabesity. One of the metabolic features in these conditions is the clinical presentation of insulin resistance. Several tissues, including the liver, skeletal muscle, and vasculature, and patients with T2DM, gestational diabetes, and obesity show insulin resistance. The vascular effect of insulin, including vasodilation, is mainly mediated by the generation of nitric oxide. Several mechanisms are proposed to elucidate the origin of insulin resistance; nevertheless, a common finding is the endothelial dysfunction in these diseases. Endothelial cells from subjects with obesity show reduced nitric oxide synthesis, an effect that is unaltered by insulin. Individuals with T2DM show a misbalance between the synthesis, release, and biological actions of vasodilators and vasoconstrictors such as nitric oxide and endothelin-1. However, whether these mechanisms are involved in the vascular alterations seen in patients with diabesity is unclear. In this review, we discussed the modifications on insulin signalling, insulin resistance in obesity and T2DM, and the reported changes in signalling pathways in diabesity., (Copyright © 2019. Published by Elsevier Ltd.)

Diabetes mellitus, obesity, and cancer are diseases that in recent years have caused a large number of deaths worldwide, so have been in the front line of biomedical research. On the other hand, obesity is a risk factor for several types of cancer and type 2 diabetes mellitus. The metabolic disorder and global inflammatory environment seen in obese patients is also critical for the treatment of both diabetes mellitus and gliomas. Several molecules are increased in patients with obesity and are considered risk factors in the failure of multimodal therapies for diabetes mellitus and gliomas. These molecules include adenosine, insulin, adenosine deaminases, adenosine kinase, lipids, as well as adenosine receptors, adenosine membrane transporters, and the immune response. The role of adenosine will be explained in depth since it is a nucleoside aberrantly increased in patients with these diseases, is one of the main causes of diabetes mellitus progression and the failure of glioma therapies. In addition, the role of type 2 diabetes mellitus/obesity, i.e., diabesity, and its implication in glioma treatment is discussed., (Copyright © 2019. Published by Elsevier Ltd.)

The last decades have been marked by an increased prevalence in non-communicable diseases such as obesity and type 2 diabetes (T2D) as well as by population aging and age-related (brain) diseases. The current notion that the brain and the body are interrelated units is gaining the attention of the scientific and medical community. Growing evidence demonstrates that there is a significant overlap in risk, comorbidity, and pathophysiological mechanisms across obesity, T2D and brain disturbances; settings that seem to be worsened when both obesity and T2D occur simultaneously, the so-called diabesity. Thereupon, there is a great concern to critically appraise and understand the mechanisms by which diabesity can affect brain responses, and may accelerate the decline in brain health. In this framework, metabolic disturbances mediated by altered insulin signaling and mitochondrial function arise among the multifactorial interactions described to occur between obesity, T2D and neurocognitive deficits. In this review we have compiled all the notions and evidence describing how diabesity negatively influences brain function putting the emphasis on insulin signaling pathway disturbances and mitochondrial anomalies. We also debate lifestyle interventions as amenable strategies to lessen metabolic anomalies and, consequently, diabesity-associated brain alterations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Diabesity, obesity, and type 2 diabetes mellitus (T2DM) are the most prevalent diseases nowadays and associate with high risk of cardiovascular complications. The impaired signalling pathways associated with the metabolism of D-glucose, lipids, and insulin have been studied for many years aiming to understand the cellular mechanisms of these diseases. Extracellular vesicles (EVs), including exosomes and microvesicles, carry different microRNAs or proteins as cargoes, acting as a mechanism of cell-to-cell communication to modulate different cell functions altering the metabolic regulatory pathways. Several studies have shown an altered number or cargo of EVs in metabolic diseases, including T2DM and obesity, suggesting that these vesicles may play an important role in the regulation of metabolic signalling pathways in diabesity. In this review, we described some of the current studies involving EVs and hypothesize about the role of these structures in the impaired metabolism in T2DM, obesity, and diabesity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Strong evidence has shown that metabolic surgery is more effective than medical treatment in the treatment of type 2 diabetic patients. However, no study demonstrated a survival benefit and reduction of diabetes-related end-organ damage. Here, we describe the study design of a large prospective cohort study, the Taiwan Diabesity Study (TDS) which would compare the long-term survival rate and end-organ damage between overweight/obese type 2 diabetic patients receiving metabolic surgery and medical treatment., Methods: Eligibility criteria include type 2 diabetic patients with duration > 6 months, body mass index (BMI) over 25 kg/m 2 and age between 20 and 67 years. Exclusion criteria are serum creatinine over 2.0 mg/dL, C-peptide below 1.0 ng/ml, recent history of cancer, and major diabetic complications. Eligible participants were recruited from six medical centers in Taiwan. The survival rate and diabetes-related end organ damage will be compared between the metabolic surgery group and medical group after follow-up for 10 years., Results: In 3 years, 1016 participants were identified from 38,751 patients. The average BMI of patients was 30.6 (±2.6) kg/m 2 and the average hemoglobin A1c was 8.2% (±1.5%) with 18% of them receiving insulin treatment. Among them, 126 patients received metabolic surgery and 890 patients received conventional medical treatment. The metabolic surgery group are younger, have a higher proportion of females, higher BMI and blood lipids as compared to the medical group., Conclusion: The TDS recruited 1016 overweight/obese type 2 diabetic patients including 126 patients receiving metabolic surgery and 890 patients receiving medical treatment., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Objectives: Diabesity (obesity and diabetes mellitus) has been identified as a potential contributor to early-onset frailty. Impairments contributing to early onset of physical frailty in this population are not well understood, and there is little evidence of the impact of peripheral neuropathy on frailty. The purpose of this study was to determine impairments that contribute to early-onset physical frailty in individuals with diabesity and peripheral neuropathy., Methods: We studied 105 participants, 82 with diabesity and peripheral neuropathy (57 years of age, body mass index [BMI] 31 kg/m 2 ); 13 with diabesity only (53 years of age, BMI 34 kg/m 2 ) and 10 obese controls (67 years of age, BMI 32 kg/m 2 ). Peripheral neuropathy was determined using Semmes Weinstein monofilaments; physical frailty was classified using the 9-item, modified Physical Performance Test; and knee extension and ankle plantarflexion peak torques were measured using isokinetic dynamometry., Results: Participants with diabesity and peripheral neuropathy were 7.4 times more likely to be classified as physically frail. Impairments in lower-extremity function were associated with classification of frailty., Conclusions: Individuals with diabesity and peripheral neuropathy are particularly likely to be classified as frail. Earlier identification and interventions aimed at improving lower-extremity function may be important to mitigate the early-onset functional decline., (Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.)

Bariatric surgery is used to induce weight loss (baros = weight). Evidence has shown that bariatric surgery improves the comorbid conditions associated with obesity such as hypertension, hyperlipidemia, and type 2 diabetes mellitus T2DM. Hence, shifting towards using metabolic surgery instead of bariatric surgery is currently more appropriate in certain subset of patients. Endocrine changes resulting from operative manipulation of the gastrointestinal tract after metabolic surgery translate into metabolic benefits with respect to the comorbid conditions. Other changes include bacterial flora rearrangement, bile acids secretion, and adipose tissue effect. The aim of this systematic review is to examine clinical trials regarding long-term effects of bariatric and metabolic surgery on patients with T2DM and to evaluate the potential mechanisms leading to the improvement in the glycaemic control.

Adipocyte fate commitment is characterized by morphological changes of fibroblastic pre-adipocyte cells, and specifically by accumulation of lipid droplets (LDs) as part of the adipogenesis metabolism. Formation of LDs indicates the production of triglycerides from glucose through an insulin-regulated glucose internalization process. In obesity, adipocytes typically become insulin resistant, and glucose transport into the cells is impaired, resulting in type 2 diabetes. In the present study, we monitored the adipogenesis in 3T3-L1 cultured cells exposed to high (450 mg/dL hyperglycemia) and low (100 mg/dL physiological) glucose concentrations, in a novel cell culture model system of diabesity. In addition to glucose conditions, cells were concurrently exposed to different substrate tensile strains (12% and control) based on our prior work which revealed that adipogenesis is accelerated in cultures subjected to static, chronic substrate tensile deformations. Phase-contrast images were taken throughout the adipogenesis process (3 weeks) and were analyzed by an image processing algorithm which quantitatively monitors cell differentiation and lipid accumulation (number of LDs per cell and their radius as well as cell size and shape). The results indicated that high glucose concentrations and substrate tensile strains delivered to adipocytes accelerated lipid production by 1.7- and 1.4-fold, respectively. In addition, significant changes in average cell projected area and in other morphological attributes were observed during the differentiation process. The importance of this study is in characterizing the adipogenesis parameters as potential read-outs that can predict the occurrence of insulin resistance in the development of diabesity.

Obesity is a prominent risk factor for type 2 diabetes. Management of type 2 diabetes requires weight management in addition to glycemic parameters. For obese type 2 diabetes patients, metformin, Sodium-glucose co-transporter-2 inhibitors or Glucagon-Like Peptide-1 Receptor Agonists should be prescribed as the first priority for controlling both hyperglycemia and body weight or fat distribution. The combination of these drugs with sulfonylureas, thiazolidinediones, and insulin may also be required in chronic cases. These drugs cause weight gain. Fortunately, many phytochemicals having a beneficial effect on diabetes and obesity, have minimum side-effects as compared to synthetic drugs. This review discusses the treatment strategies for controlling glycemia and weight management, with the focus on anti-diabetic drugs and phytochemicals. Glucagonostatic role, activation of Adenosine monophosphate-activated protein kinase and adipocyte targeting potential of anti-diabetic drugs and phytochemicals are also discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Diabesity-obesity resulting in diabetes-is a major health problem globally because of the obesity epidemic. Several anti-diabetic medications cause weight gain and may worsen obesity, and possibly diabeisty. Two recent small retrospective cohort studies showed weight loss and diabetes improvement with combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type-2 (SGLT-2) inhibitors in obese subjects. We assessed the effect of combination therapy with GLP-1 agonists and SGLT-2 inhibitors in the management of diabesity in a retrospective study at the Wolverhampton Diabetes Centre. Out of 79 patients on this combination regimen with other anti-diabetic medications, 37 cases who had follow up at 3-6 months were studied. Mean age and duration of follow up were 57.4 (+/-7.8) and 139 (+/-32.6) days, respectively. Twenty-two patients (59.5 %) were Asians. Statistically significant improvements in clinical parameters such as body weight reduction (3.07 kg), glycated haemoglobin (HbA1c) reduction (1.05 %), lower BMI (-1.13 kg/M 2 ) and insulin dose reduction (6.8 units) were observed (p < 0.05 for all) in patients on combination regimen. Linear regression analysis showed that baseline HbA1c and baseline insulin dose were independent predictors of HbA1c reduction and insulin dose reduction, respectively. Our results suggest that combination therapy with GLP-1 agonists and SGLT-2 inhibitors is a promising option for patients with diabesity.

Obesity is a chronic metabolic disease affecting adults and children worldwide. It has become one of the leading causes of death, as obesity is known to be the main risk factor for a number of non-communicable diseases, in particular type 2 diabetes. This close relationship led to the connotation 'diabesity', highlighting the fact that the majority of individuals with diabetes are overweight or obese. Until today the BMI is still used to classify overweight and obesity. Since reduced muscle mass is highly prevalent throughout the BMI range, the measurement of body composition is strongly recommended. Moreover, it is essential for monitoring the course of weight reduction, which is part of every effective anti-obesity treatment. Weight reduction can be achieved via different weight loss strategies, including lifestyle intervention (diet and exercise), pharmacotherapy, or bariatric surgery. However, not all of these strategies are suitable for all patients, and any further needs should be considered. Besides, attention should also be drawn to concomitant therapies. These therapies may promote additional weight gain and further trigger the deterioration of blood glucose control. Thus, therapeutic strategies are warranted, which can be easily used for the management of obese patients with type 2 diabetes to achieve their glycemic and weight loss goals., (© 2017 The Author(s) Published by S. Karger GmbH, Freiburg.)

It is widely accepted that high calorie diets and a sedentary lifestyle sturdily influence the incidence and outcome of type 2 diabetes and obesity, which can occur simultaneously, a situation called diabesity. Tightly linked with metabolic and energy regulation, a close association between diabetes and Alzheimer's disease (AD) has been proposed. Among the common pathogenic mechanisms that underpin both conditions, insulin resistance, brain glucose hypometabolism, and metabolic dyshomeostasis appear to have a pivotal role. This century is an unprecedented diabetogenic period in human history, so therapeutic strategies and/or approaches to control and/or revert this evolving epidemic is of utmost importance. This chapter will make a brief contextualization about the impact that diabetes and obesity can exert in brain structure and function alongside with a brief survey about the role of insulin in normal brain function, exploring its roles in cognition and brain glucose metabolism. Later, attention will be given to the intricate relation of diabesity, insulin resistance, and AD. Finally, both pharmacological and lifestyle interventions will also be reviewed as strategies aimed at fighting diabesity and/or AD-related metabolic effects.

The prevalence of diabetes and adiposity has increased at an alarming rate and together they contribute to the rise in morbidity and mortality worldwide. Genetic studies till date have succeeded in explaining only a proportion of heritability, while a major component remains unexplained. Early life determinants of future risk of these diseases are likely contributors to the missing heritability and thus have a significant potential in disease prevention. Epidemiological and animal studies show the importance of intrauterine and early postnatal environment in programming of the fetus to adverse metabolic outcomes and support the notion of Developmental Origins of Health and Disease (DOHaD). Emerging evidence highlights the role of epigenetic mechanisms in mediating effects of environmental exposures, which in certain instances may exhibit intergenerational transmission even in the absence of exposure. In this article, we will discuss the complexity of diabetes and increased adiposity and mechanisms of programming of these adverse metabolic conditions.