Effect of bariatric surgery on metabolism in diabetes and obesity comorbidity:Insight from recent research

Obesity is a prevalent cause of diabetes mellitus(DM)and is a serious danger to human health.Type 2 DM(T2DM)mostly occurs along with obesity.Foodborne obesity-induced DM is caused by an excessive long-term diet and surplus energy.Bariatric surgery can improve the symptoms of T2DM in some obese patients.But different types of bariatric surgery may have different effects.There are some models built by researchers to discuss the surgical procedures’effects on me-tabolism in diabetes animal models and diabetes patients.It is high time to conclude all this effects and recommend procedures that can better improve metabolism.

The Association between GLP-1 Receptor-Based Agonists and the Incidence of Asthma in Patients with Type 2 Diabetes and/or Obesity:A Meta-Analysis

Objective Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists(GLP-1RAs)on asthma,which is often comorbid with type 2 diabetes mellitus(T2DM)and obesity.Therefore,we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1(GLP-1)receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity.Methods PubMed,Web of Science,Embase,the Cochrane Central Register of Controlled Trials,and Clinicaltrial.gov were systematically searched from inception to July 2023.Randomized controlled trials(RCTs)of GLP-1 receptor-based agonists(GLP-1RA,GLP-1 based dual and triple receptor agonist)with reports of asthma events were included.Outcomes were computed as risk ratios(RR)using a fixedeffects model.Results Overall,39 RCTs with a total of 85,755 participants were included.Compared to non-GLP-1 receptor-based agonist users,a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments,although the difference was not statistically significant[RR=0.91,95%confidence interval(CI):0.68 to 1.24].Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users(RR=0.65,95%CI:0.43 to 0.99,P=0.043).We also performed sensitivity analyses for participant characteristics,study design,drug structure,duration of action,and drug subtypes.However,no significant associations were observed.Conclusion Compared with non-users,a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments.Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.

Drawing lines in the sand: The growing threat of obesity in type 1 diabetes

In this editorial,we comment on the article by Zeng et al published in the recent issue of the World Journal of Diabetes in 2024.We focus on the epidemiological,pathophysiological,and clinical interplay between obesity and type 1 diabetes mellitus(T1DM).Overweight and obesity represent a growing threat for modern societies and people with T1DM could not be an exception to this rule.Chronic exogenous insulin administration,genetic and epigenetic factors,and psy-chosocial and behavioral parameters,along with the modern way of life that incorporates unhealthy eating patterns and physical inactivity,set the stage for the increasing obesity rates in T1DM.As our knowledge of the underlying mechanisms that lead to the development of obesity and hyperglycemia expands,it becomes clear that there are overlap zones in the pathophysiology of the two main types of diabetes.Stereotypes regarding strict dividing lines between“autoimmune”and“metabolic”phenotypes increase the risk of trapping physicians into ineffective therapeutic approaches,instead of individualized diabetes care.In this context,the use of adjuncts to insulin therapy that have the potential to alleviate cardiorenal risk and decrease body weight can reduce the burden of obesity in patients with T1DM.

Diabetes and obesity:A debate on bariatric interventions and its implications

In this editorial,we comment on an article by Tang et al published in the World Journal of Diabetes.Obesity and diabetes are two pathological situations that are intrinsically related.Neither lifestyle changes nor pharmacological treatments have achieved diabetes remission.From this perspective,bariatric surgery has been widely used as an approach for weight loss in obese patients and as a strategy to promote metabolic modulation.The main effects of bariatric surgery involve direct action in improving cardiovascular function and endothelial function and reducing insulin resistance,leading to diabetes remission in the short term following surgery.In this context,it has been observed that hormones from the gastrointestinal tract and endothelium play a prominent role in this process.By reversing endothelial dysfunction,it is possible to balance pro-inflammatory cytokine production,improving the availability of nitric oxide and inhibiting vascular oxidative stress.Furthermore,it can be considered an efficient anti-inflammatory strategy,alleviating interferon-gamma-mediated adipose tissue inflammation.The current challenge must be to unravel the pathophysiological mechanisms and potential targets for treating metabolic diseases.

Surgical or medical treatment of obesity-associated type 2 diabetesan increasing clinical conundrum

In this editorial,we comment on the article by He et al,specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist(GLP-1RA)therapy in the management of type 2 diabetes(T2D)associated with obesity.Bariatric surgery has now also been shown to be safe and effective in pre-teens and teenagers with obesity and T2D,but information on newer GLP-1RAs in these groups is predictably limited.In older individuals(age>65 years),both bariatric surgery and GLP-1RA therapy improve cardiovascular outcomes.Baria-tric surgery is not infrequently associated with post-operative postprandial hypoglycemia,which is not the case with GLP-1RAs and,paradoxically,there is evidence that GLP-1RAs may reduce both the frequency and severity of postprandial hypoglycemia.Comparative trials of the long-term efficacy of bariatric surgery and GLP-1RAs are indicated.

Analysis of the Correlation Between Visceral Fat Area and Insulin Resistance in Patients with Type 2 Diabetes and Abdominal Obesity

Objective: To analyze the correlation between visceral fat area and insulin resistance index (HOMA-IR) in patients with type 2 diabetes mellitus (T2DM) and abdominal obesity and to provide a reference for screening and related research of such patients. Methods: Two hundred patients with T2DM admitted to Guandu People’s Hospital of Kunming were included. The study was carried out from October 2022 to December 2023. The patients were divided into three groups according to different abdominal visceral fat areas (VFA): Group A (n = 65) was less than 75cm2, Group B (n = 75) was 75-100 cm2, and Group C (n = 60) was greater than 100 cm2. The subjects in the three groups were all tested for glycated hemoglobin (HbA1c), fasting insulin (FINS), and fasting blood glucose (FPG). Height and weight were measured to calculate body mass index (BMI). The HOMA-IR and TYG (fasting triglyceride and glycemic index) were also calculated. Changes in the BMI, VFA, HOMA-IR, and TYG levels were observed in the three groups. Results: The VFA, BMI, HbA1c, FPG, FINS, HOMA-IR, and TYG of the patients all increased, with a more significant increase in the BMI, FINS, HOMA-IR, and TYG levels (P < 0.01). Multiple linear stepwise regression analyses used visceral fat area (VFA) as the dependent variable. The results showed that VFA was closely related to BMI, FINS, HOMA-IR, and TYG. Conclusion: Early reduction of VFA to reduce insulin resistance may be a better treatment and effective method for T2DM, providing powerful measures and new strategies for effective blood sugar control and early prevention in the treatment of metabolic diseases.

MiRNA-200a and miRNA-200b expression,and vitamin-D level:Prognostic significance in obese non-diabetic and obese type 2 diabetes mellitus individuals

BACKGROUND Obesity and type 2 diabetes mellitus(T2DM)are frequent co-occurring disorders that affect regular metabolic functions.Obesity has also been linked to an inc-reased risk of developing diabetes.Obesity and diabetes are on the rise,increa-sing healthcare costs and raising mortality rates.Research has revealed that the expression profile of microRNAs(miRNAs)changes as diabetes progresses.Fur-thermore,vitamin D may have an anti-obesity effect and inverse association with body weight and body mass index(BMI).Low vitamin D levels do not solely cause obesity,which could be a factor in the etiology of T2DM.METHODS This study included 210 participants,of which,82 were obese(BMI>30 kg/m2)without T2DM,28 were obese with T2DM,and 100 were healthy controls.BMI was evaluated and both fasting and postprandial blood glucose were used to confirm T2DM.Exosomal miRNA-200a and miRNA-200b expression were analyzed using real-time PCR using Taqman probes,and vitamin-D levels were evaluated using an electrochemiluminescence-based immunoassay technique.All data analyses were performed using SPSS 20.0 and GraphPad Prism 5 software.RESULTS Overall,a 2.20-and 4.40-fold increase in miRNA-200a and miRNA-200b expression was observed among participants compared to healthy controls.MiRNA-200a and miRNA-200b expression among obese participants increased 2.40-fold and 3.93-fold,respectively,while in obese T2DM participants these values were 2.67-fold,and 5.78-fold,respectively,and these differences were found to be statistically significant(P=0.02)(P<0.0001).Obese participants showed a vitamin D level of 34.27 ng/mL,while in obese-T2DM participants vitamin D level was 22.21 ng/mL(P<0.0001).Vitamin D was negatively correlated with miRNA-200a(r=-0.22,P=0.01)and miRNA-200b(r=-0.19,P=0.04).MiRNA-200a sensitivity was 75%,and specificity was 57%,with a cutoff value of 2.07-fold.MiRNA-200b sensitivity was 75%,and specificity was 71%with a cutoff value of 4.12-fold,suggesting that miRNA-200a and miRNA-200b with an increased expression of 2.07-and 4.12-fold could be predictive indicators for the risk of diabetes in obese participants.CONCLUSION MiRNA-200a and miRNA-200b were higher in diabetic obese participants vs non-diabetic obese participants,and insufficient vitamin D levels in obese T2DM participants may be involved in poor clinical outcome.

High-fat diet and oral infection induced type 2 diabetes and obesity development under different genetic backgrounds

Background:Type 2 diabetes(T2D)is an adult-onset and obese form of diabetes caused by an interplay between genetic,epigenetic,and environmental components.Here,we have assessed a cohort of 11 genetically different collaborative cross(CC)mouse lines comprised of both sexes for T2D and obesity developments in response to oral infection and high-fat diet(HFD)challenges.Methods:Mice were fed with either the HFD or the standard chow diet(control group)for 12 weeks starting at the age of 8 weeks.At week 5 of the experiment,half of the mice of each diet group were infected with Porphyromonas gingivalis and Fusobacterium nucleatum bacteria strains.Throughout the 12-week experimental period,body weight(BW)was recorded biweekly,and intraperitoneal glucose tolerance tests were performed at weeks 6 and 12 of the experiment to evaluate the glucose tolerance status of mice.Results:Statistical analysis has shown the significance of phenotypic variations between the CC lines,which have different genetic backgrounds and sex effects in different experimental groups.The heritability of the studied phenotypes was estimated and ranged between 0.45 and 0.85.We applied machine learning methods to make an early call for T2D and its prognosis.The results showed that classification with random forest could reach the highest accuracy classification(ACC=0.91)when all the attributes were used.Conclusion:Using sex,diet,infection status,initial BW,and area under the curve(AUC)at week 6,we could classify the final phenotypes/outcomes at the end stage of the experiment(at 12 weeks).

Diabetes exacerbates inflammatory bowel disease in mice with dietinduced obesity

BACKGROUND The increased prevalence of inflammatory bowel disease(IBD)among patients with obesity and type 2 diabetes suggests a causal link between these diseases,potentially involving the effect of hyperglycemia to disrupt intestinal barrier integrity.AIM To investigate whether the deleterious impact of diabetes on the intestinal barrier is associated with increased IBD severity in a murine model of colitis in mice with and without diet-induced obesity.METHODS Mice were fed chow or a high-fat diet and subsequently received streptozotocin to induce diabetic-range hyperglycemia.Six weeks later,dextran sodium sulfate was given to induce colitis.In select experiments,a subset of diabetic mice was treated with the antidiabetic drug dapagliflozin prior to colitis onset.Endpoints included both clinical and histological measures of colitis activity as well as histochemical markers of colonic epithelial barrier integrity.RESULTS In mice given a high-fat diet,but not chow-fed animals,diabetes was associated with significantly increased clinical colitis activity and histopathologic markers of disease severity.Diabetes was also associated with a decrease in key components that regulate colonic epithelial barrier integrity(colonic mucin layer content and epithelial tight junction proteins)in diet-induced obese mice.Each of these effects of diabetes in diet-induced obese mice was ameliorated by restoring normoglycemia.CONCLUSION In obese mice,diabetes worsened clinical and pathologic outcomes of colitis via mechanisms that are reversible with treatment of hyperglycemia.Hyperglycemia-induced intestinal barrier dysfunction offers a plausible mechanism linking diabetes to increased colitis severity.These findings suggest that effective diabetes management may decrease the clinical severity of IBD.

Mechanism of immune attack in the progression of obesity-related type 2 diabetes

Obesity and overweight are widespread issues in adults,children,and adolescents globally,and have caused a noticeable rise in obesity-related complications such as type 2 diabetes mellitus(T2DM).Chronic low-grade inflammation is an important promotor of the pathogenesis of obesity-related T2DM.This proinflammatory activation occurs in multiple organs and tissues.Immune cellmediated systemic attack is considered to contribute strongly to impaired insulin secretion,insulin resistance,and other metabolic disorders.This review focused on highlighting recent advances and underlying mechanisms of immune cell infiltration and inflammatory responses in the gut,islet,and insulin-targeting organs(adipose tissue,liver,skeletal muscle)in obesity-related T2DM.There is current evidence that both the innate and adaptive immune systems contribute to the development of obesity and T2DM.

Physiopathological mechanisms related to inflammation in obesity and type 2 diabetes mellitus

Overweight,obesity,and type 2 diabetes mellitus pose global health problems that are ever-increasing.A chronic low-grade inflammatory status and the presence of various pro-inflammatory markers either in circulation or within dysfunctional metabolic tissues are well established.The presence of these factors can,to some extent,predict disease development and progression.A central role is played by the presence of dysfunctional adipose tissue,liver dysfunction,and skeletal muscle dysfunction,which collectively contribute to the increased circulatory levels of proinflammatory factors.Weight loss and classical metabolic interventions achieve a decrease in many of these factors’circulating levels,implying that a better understanding of the processes or even the modulation of inflammation may alleviate these diseases.This review suggests that inflammation plays a significant role in the development and progression of these conditions and that measuring inflammatory markers may be useful for assessing disease risk and development of future treatment methods.

Destabilization of HIF-1a by Diabetes, Oxidative Stress, Obesity and Other Related Disorders

One of the most fundamental molecular processes in response to hypoxia is the activation and stabilization of a transcriptional factor called hypoxia induced factor 1a (HIF-1a), which is responsible for the regulation of many downstream effector genes. Multiple key biological pathways such as proliferation, energy metabolism, invasion, and metastasis are governed by these genes. This article discusses the role of hypoxia-inducible factor 1a (HIF-1a) in metabolic and pathological processes, particularly in adipose tissue, oxidative stress, inflammation, diabetes and cancer. HIF1A is a basic helix-loophelix PAS domain containing protein, and is considered as the master transcriptional regulator of cellular and developmental response to hypoxia. HIF-1a regulates the expression of genes involved in angiogenesis, glucose metabolism, inflammation and oxidative stress. In obesity, adipose tissue hypoxia leads to increased expression of HIF-1a, which can lead to chronic inflammation and adipose tissue dysfunction. Another field that HIF-1a is also involved in cancer pathogenesis pathways, such as proliferation, invasion, angiogenesis, and metastasis, and is considered a potential therapeutic target for metabolic/genetic diseases and cancer. Direct and indirect HIF-1 inhibitors have been identified, but only a few have entered clinical trials due to their multiple side effects.

Molecular mechanisms of noncoding RNA and epigenetic regulation in obesity with consequent diabetes mellitus development

Diabetes mellitus(DM)and obesity have become two of the most prevalent and challenging diseases worldwide,with increasing incidence and serious complications.Recent studies have shown that noncoding RNA(ncRNA)and epigenetic regulation play crucial roles in the pathogenesis of DM complicated by obesity.Identification of the involvement of ncRNA and epigenetic regulation in the pathogenesis of diabetes with obesity has opened new avenues of investigation.Targeting these mechanisms with small molecules or RNA-based therapies may provide a more precise and effective approach to diabetes treatment than traditional therapies.In this review,we discuss the molecular mechanisms of ncRNA and epigenetic regulation and their potential therapeutic targets,and the research prospects for DM complicated with obesity.

Implications of receptor for advanced glycation end products for progression from obesity to diabetes and from diabetes to cancer

Obesity and type 2 diabetes mellitus(T2DM)are chronic pathologies with a high incidence worldwide.They share some pathological mechanisms,including hyperinsulinemia,the production and release of hormones,and hyperglycemia.The above,over time,affects other systems of the human body by causing tissue hypoxia,low-grade inflammation,and oxidative stress,which lay the pathophysiological groundwork for cancer.The leading causes of death globally are T2DM and cancer.Other main alterations of this pathological triad include the accumulation of advanced glycation end products and the release of endogenous alarmins due to cell death(i.e.,damage-associated molecular patterns)such as the intracellular proteins high-mobility group box protein 1 and protein S100 that bind to the receptor for advanced glycation products(RAGE)-a multiligand receptor involved in inflammatory and metabolic and neoplastic processes.This review analyzes the latest advanced reports on the role of RAGE in the development of obesity,T2DM,and cancer,with an aim to understand the intracellular signaling mechanisms linked with cancer initiation.This review also explores inflammation,oxidative stress,hypoxia,cellular senescence,RAGE ligands,tumor microenvironment changes,and the“cancer hallmarks”of the leading tumors associated with T2DM.The assimilation of this information could aid in the development of diagnostic and therapeutic approaches to lower the morbidity and mortality associated with these diseases.

Bariatric surgery and diabetes:Current challenges and perspectives

Diabetes mellitus(DM)and obesity have become public issues of global concern.Bariatric surgery for the treatment of obesity combined with type 2 DM has been shown to be a safe and effective approach;however,there are limited studies that have systematically addressed the challenges of surgical treatment of obesity combined with DM.In this review,we summarize and answer the most pressing questions in the field of surgical treatment of obesity-associated DM.I believe that our insights will be of great help to clinicians in their daily practice.

Insulin resistance as the molecular link between diabetes and Alzheimer's disease

Diabetes mellitus(DM)and Alzheimer's disease(AD)are two major health concerns that have seen a rising prevalence worldwide.Recent studies have indicated a possible link between DM and an increased risk of developing AD.Insulin,while primarily known for its role in regulating blood sugar,also plays a vital role in protecting brain functions.Insulin resistance(IR),especially prevalent in type 2 diabetes,is believed to play a significant role in AD's development.When insulin signalling becomes dysfunctional,it can negatively affect various brain functions,making individuals more susceptible to AD's defining features,such as the buildup of beta-amyloid plaques and tau protein tangles.Emerging research suggests that addressing insulin-related issues might help reduce or even reverse the brain changes linked to AD.This review aims to explore the relationship between DM and AD,with a focus on the role of IR.It also explores the molecular mechanisms by which IR might lead to brain changes and assesses current treatments that target IR.Understanding IR's role in the connection between DM and AD offers new possibilities for treatments and highlights the importance of continued research in this interdisciplinary field.

Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

BACKGROUND Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus(T2DM),that is,patients who have insulin resistance,obesity,and other cardiovascular risk factors,suggesting that the presence of glutamic acid decarboxylase(anti-GAD65),islet antigen 2(anti-IA2),and zinc transporter 8(anti-Zn8T)antibodies could have deleterious effects on beta cell function,causing failure and earlier requirement for insulin treatment.AIM To evaluate anti-GAD65,anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of T2DM.METHODS This was a case–control study in patients with clinically diagnosed with T2DM(68 cases and 64 controls with and without early insulin dependence respectively),male and female,aged 12–18 years.Somatometry,blood pressure,glucose,insulin,C-peptide,glycated hemoglobin A1c,and lipid profiles were assessed.ELISA was used to measure anti-GAD65,anti-IA2,and anti-Zn8T antibodies.Descriptive statistics,Pearson'sχ2 test,Student's t test,and logistic regression was performed.P<0.05 was considered statistically significant.RESULTS There were 132 patients(53.8%female),with a mean age was 15.9±1.3 years,and there was a disease evolution time of 4.49±0.88 years.The presence of anti-GAD65,anti-IA2,and anti-Zn8T positivity was found in 29.5%,18.2%,and 15.9%,respectively.Dividing the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity:anti-GAD65 odds ratio(OR):2.42(1.112–5.303,P=0.026);anti-IA2:OR:1.55(0.859–2.818,P=0.105);and anti-Zn8T:OR:7.32(2.039–26.279,P=0.002).CONCLUSION Anti-GAD65 positivity was high in our study.Anti-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype,leading to an increased risk of early insulin dependence.

Impact of body mass index on adverse kidney events in diabetes mellitus patients: A systematic-review and meta-analysis

BACKGROUND The incidence of chronic kidney disease among patients with diabetes mellitus(DM)remains a global concern.Long-term obesity is known to possibly influence the development of type 2 diabetes mellitus.However,no previous meta-analysis has assessed the effects of body mass index(BMI)on adverse kidney events in patients with DM.AIM To determine the impact of BMI on adverse kidney events in patients with DM.METHODS A systematic literature search was performed on the PubMed,ISI Web of Science,Scopus,Ovid,Google Scholar,EMBASE,and BMJ databases.We included trials with the following characteristics:(1)Type of study:Prospective,retrospective,randomized,and non-randomized in design;(2)participants:Restricted to patients with DM aged≥18 years;(3)intervention:No intervention;and(4)kidney adverse events:Onset of diabetic kidney disease[estimated glomerular filtration rate(eGFR)of<60 mL/min/1.73 m2 and/or microalbuminuria value of≥30 mg/g Cr],serum creatinine increase of more than double the baseline or end-stage renal disease(eGFR<15 mL/min/1.73 m2 or dialysis),or death.RESULTS Overall,11 studies involving 801 patients with DM were included.High BMI(≥25 kg/m2)was significantly associated with higher blood pressure(BP)[systolic BP by 0.20,95%confidence interval(CI):0.15–0.25,P<0.00001;diastolic BP by 0.21 mmHg,95%CI:0.04–0.37,P=0.010],serum albumin,triglycerides[standard mean difference(SMD)=0.35,95%CI:0.29–0.41,P<0.00001],low-density lipoprotein(SMD=0.12,95%CI:0.04–0.20,P=0.030),and lower high-density lipoprotein(SMD=–0.36,95%CI:–0.51 to–0.21,P<0.00001)in patients with DM compared with those with low BMIs(<25 kg/m2).Our analysis showed that high BMI was associated with a higher risk ratio of adverse kidney events than low BMI(RR:1.22,95%CI:1.01–1.43,P=0.036).CONCLUSION The present analysis suggested that high BMI was a risk factor for adverse kidney events in patients with DM.

Adiposity in Chinese people with type 1 diabetes

Adiposity,synonymous with obesity,is prevalent among both children and adults with type 1 diabetes in China.Recent literature underscored the pathophysiological and socioeconomic factors associated with adiposity,and consistently highlighted its impact on cardiovascular,kidney,and metabolic diseases among Chinese individuals with type 1 diabetes.Addressing and managing adiposity in individuals with type 1 diabetes are complicated and entail comprehensive approaches including lifestyle modifications,cognitive-behavioral therapy,insulin dose titration,and other diabetes treatment medications.The condition calls for coordination among policymakers,researchers,clinicians,and patients.

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

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