Diabetes Obesity Research Articles

Neuroprotective effects of GLP-1 receptor agonists in neurodegenerative Disorders: A Large-Scale Propensity-Matched cohort study

BackgroundGLP-1 receptor agonists, traditionally used for treating type 2 diabetes mellitus and obesity, have demonstrated anti-inflammatory properties. However, their potential neuroprotective effects in neurodegenerative disorders remain unclear. ObjectiveTo evaluate the impact of GLP-1 receptor agonists on the risk of developing various neurodegenerative conditions in obese patients. MethodsThis comprehensive retrospective cohort study analyzed data from 5,307,845 obese adult patients across 73 healthcare organizations in 17 countries. Propensity score matching was performed, resulting in 102,935 patients in each cohort. We compared the risk of developing neurodegenerative disorders between obese patients receiving GLP-1 receptor agonist therapy and those who were not. ResultsObese patients treated with GLP-1 receptor agonists showed significantly lower risks of developing Alzheimer’s disease (RR = 0.627, 95 %CI = 0.481–0.817), Lewy body dementia (RR = 0.590, 95 %CI = 0.462–0.753), and vascular dementia (RR = 0.438, 95 %CI = 0.327–0.588). The risk reduction for Parkinson’s disease was not statistically significant overall (RR = 0.784, 95 %CI = 0.580–1.058) but was significant for semaglutide users (RR = 0.574, 95 %CI = 0.369–0.893). Semaglutide consistently showed the most pronounced protective effects across all disorders. Additionally, a significant reduction in all-cause mortality was observed (HR = 0.525, 95 %CI = 0.493–0.558). ConclusionThis study provides evidence that the effects of GLP-1 receptor agonists may extend beyond their known metabolic and cardioprotective benefits to include neuroprotection, associated with a decreased risk of developing various neurodegenerative disorders. These findings suggest the potential for expanding the therapeutic applications of GLP-1 receptor agonists to improve neurocognitive outcomes. Further research is warranted to elucidate the mechanisms underlying these neuroprotective effects and to explore their clinical applications in neurodegenerative disease prevention and treatment.

Effectiveness and Safety of GLP-1 Receptor Agonists in Patients with Type 1 Diabetes.

Background: GLP-1 receptor agonists (GLP-1RA) are used in the management of type II diabetes mellitus or obesity, although its role in patients with type I diabetes mellitus (T1DM) has been debated. This study aimed to investigate the efficacy and safety of GLP-1RA in patients with T1DM using real-world data. Methods: This multicenter, retrospective study was conducted at three tertiary medical centers in Riyadh, Saudi Arabia. The study followed up patients (>16 years old) with T1DM treated with insulin followed by GLP-1RA add-on therapy. The efficacy outcomes included changes in HbA1c, body weight, and insulin requirements from baseline to each follow-up visit. The main safety outcomes assessed included hypoglycemic events and gastrointestinal (GI) adverse events. Results: The study included 144 patients with a mean age of 33.0 ± 10.1 years. Semaglutide was the most used GLP-1RA (63.9%) followed by liraglutide (34.0%). From baseline to 3-month follow-up, HbA1c (mean difference (MD) = -0.8%; p = 0.0053), weight (MD = -2.4 kg; p = 0.0253), and daily basal insulin dose (MD = -2.1 units; p = 0.0349) were significantly reduced. Likewise, HbA1c (MD = -0.5%; p = 0.0004), weight (MD = -3.6 kg; p < 0.0001), and daily basal insulin (MD = -2.4 units; p = 0.0282) were significantly reduced at the 4-6-month follow-up. The significant reductions in HbA1c, weight, and daily basal insulin levels were consistent for up to 18-month follow-up. Only one patient had a major hypoglycemic event, whereas 8.3% of the patients had GI adverse events. Conclusions: Overall, significant improvements in glycemic control, weight loss, and insulin requirements were observed with the use of GLP-1RA in patients with T1DM, with a limited number of GI adverse events.

Association of Risk Factors of Acute Myocardial Infarction and Heart Blockage Among non-diabetic Patients in a Tertiary Care Hospital – An Observational Study

Introduction: Cardiovascular diseases (CVDs) are a leading cause of death in the world. In 2015, an estimated 442.7 million prevalent cases of CVD were present worldwide. Cardiovascular diseases account for more than 17 million deaths globally each year. Previous studies identified diabetes mellitus, hypertension, hypercholesterolemia, smoking, alcohol consumption, obesity and sedentary lifestyle as risk factors. Aim of the study: The aim of this study was to determine the risk factors for acute myocardial infarction associated with heart blockage among non-diabetic patients. Methods: This was an observational study conducted in the Department of Cardiology of Jashore Medical College Sadar Hospital, Jashore, Bangladesh during the period from April, 2021 to March, 2022. In this study, we included 120 non-diabetic patients who were diagnosed with myocardial infarction. Result: Mean age was 53.03±11.3 years &amp; most of our patients were male. Among all patients, majority (65%) patients had &gt;60% blockage, followed by 30(25%) patients had 40%-60% artery blockage, and &lt;40% blockage was found in 10% patients. Hypertension, dyslipidemia &amp; dyslipidemia with hypertension, age ≥60 years, family history of CHD, smoking, diabetes &amp; obesity were individual risk factors of CHD among non-diabetic patients. The most common risk factors for heart blockage were age &gt;45 years, high blood pressure, high LDL, unhealthy diet, and stressful life. Conclusion: In our study, we found hypertension, history of CHD, dyslipidemia, dyslipidemia with hypertension, stress, age ≥60 years, and obesity were individual risk factors for CHD. These elements work as crucial risk factors for myocardial infarction in non-diabetic patients. Risk factors like age &gt;45 years, high blood pressure, high LDL, unhealthy diet, and stressful life were responsible for the highest heart blockage in myocardial infarction patients. J Inv Clin Cardiol 2023; 5(2): 38-44

Anti-inflammatory effect of semaglutide: updated systematic review and meta-analysis

Abstract Background Glucagon-like peptide-1 (GLP-1RA) receptor agonists possess multiple favourable metabolic, anti-inflammatory effects and their use is associated with marked body weight reduction. More importantly, this drug class has been shown to reduce cardiovascular events in patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk or with established cardiovascular disease. Accordingly, current guidelines recommend the use of GLP-1RA sas first-line antidiabetic therapies in patients at high cardiovascular risk. Semaglutide is a potent GLP-1RA used in the treatment of T2DM with proven cardiovascular benefits. It is currently available in formulations for oral and subcutaneous administration. The anti-inflammatory effect could be one of the mechanisms by which semaglutide reduces cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) and/or obesity. Determining the anti-inflammatory effect of semaglutide was the objective of this systematic review and meta-analysis. Methods This meta-analysis was performed according to the PRISMA guidelines. A literature search was performed to detect randomised clinical trials that have quantified the effect of semaglutide on C-reactive protein (CRP) levels compared to placebo or a control group (other glucose-lowering drugs). The primary outcome was CRP index (final CRP/basal CRP). A random-effects model was used. Results Overall, this meta-analysis shows that semaglutide therapy was associated with lower CRP index values compared to placebo (SMD -0.56; 95% CI -0.69 to -0.43, I2 92%) or when comparing semaglutide treatment versus a control group consisting of patients medicated with other glucose-lowering drugs (SMD -0.45; 95% CI -0.68 to -0.23, I 3 82%). The stratified analysis was performed by analysing only the trials that used a placebo group as comparator, When the trials were analysed according to the different dosing schemes (subcutaneous vs. oral), the results were not statistically significantly different (oral semaglutide group: SMD -0.33; 95% CI -0.75 to 0.08, I2 95%); semaglutide subcutaneous dose group: SMD -0.69; 95% CI -0.78 to -0.60, I2 74%); interaction p = 0.098. Furthermore, when the trials were analysed according to the included populations (patients with or without T2DM), the results were similar (patients with T2DM: SMD -0.32; 95% CI -0.51 to -0.14, I2 86%); patients without T2DM: SMD -0.82; 95% CI -0.90 to -0.74, I2 58%); interaction p = &amp;lt; 0.0001. Conclusion The present meta-analysis demonstrated that the use of semaglutide was associated with a reduction in inflammation irrespective of the population evaluated or the treatment regimen used. These findings would explain one of the mechanisms by which semaglutide reduces cardiovascular events.

Exploring heart failure prevalence and overlooked dimensions: a comprehensive NT Pro-BNP study in high-risk primary care patients

Abstract Background Heart failure (HF) is a prevalent syndrome linked to significant morbidity and mortality, especially in those with comorbid conditions like diabetes, hypertension, and atherosclerotic cardiovascular disease. Early detection and intervention are crucial. Natriuretic peptides, particularly NT-proBNP, are promising biomarkers for identifying at-risk individuals, but their use in primary care settings is not fully understood. Methods This prospective cohort study enrolled 874 participants aged 40 and above with documented risk factors for HF, such as diabetes mellitus, hypertension, metabolic syndrome, obesity, atherosclerotic cardiovascular disease, genetic variants for cardiomyopathy, or exposure to cardiotoxic agents. NT-proBNP levels were measured in blood samples collected at primary care clinics, and participants underwent comprehensive cardiac evaluations at a referral hospital. Clinical characteristics, laboratory findings, electrocardiography, and echocardiography results were recorded. Results The study included 874 patients with at least one risk factor for HF, with a mean age of 62.5 ± 9.1 years and 51.9% female. According to the 2022 AHA/ACC/HFSA HF Guideline, 69.1% were Stage A HF, 21.9% Stage B HF, and 9% Stage C HF. Clinical characteristics, laboratory and echocardiographic findings are shown in Picture 1. The majority had hypertension (71.1%), while other prevalent comorbidities included diabetes mellitus (43.4%), dyslipidemia (35.2%), obesity (27.1%), and atherosclerotic cardiovascular disease (26.2%). Laboratory findings showed a significant decrease in HbA1C, eGFR, LDL, triglycerides, and hemoglobin from Stage A to C HF. Median NT-proBNP levels rose from Stage A to C HF (46.4 pg/mL in Stage A, 219 pg/mL in Stage B, and 268.5 pg/mL in stage C), with 84.8% of Stage B HF patients exhibiting elevated levels. NT-proBNP levels were correlated positively with left atrial volume index, left ventricular mass index, age, E/e’, and estimated systolic pulmonary artery pressure levels. Conversely, NT-proBNP levels showed a negative correlation with estimated glomerular filtration rate and left ventricular ejection fraction. Among Stage C patients, 92.4% had HFpEF. The Picture 2 depicted the study's design and outcomes, providing a comprehensive visual representation. Conclusion NT-proBNP screening in primary care settings identified a substantial proportion of individuals with undiagnosed HF, particularly those in Stage B and Stage C. The high prevalence of HFpEF underscores the need for comprehensive evaluation and management strategies targeting this population. Early detection facilitated by NT-proBNP screening may lead to timely interventions and improved outcomes in individuals at risk for HF.

Prevalence and accumulation of metabolic risk factors of cardiovascular disease in Finland

Abstract Background Cardiovascular disease (CVD) remains the leading cause of death and disability in the world. We aimed to examine the prevalence of metabolic risk factors of CVD and their accumulation in the Finnish working-age population. Materials and methods The data consisted of individuals aged 20 to 69 who participated in the population-based Healthy Finland health examination survey in 2023 (n = 4375; participation rate 56%). We studied the accumulation of four risk factors: hypertension, hypercholesterolemia, diabetes and central obesity. The information was collected using health examination measurements and blood samples. Information on medical conditions and medication use was collected using questionnaires and national register data. All analyses utilized weighting coefficients. Adjusted results (age, sex) were calculated via logistic regression. Results The most common CVD risk factor was hypercholesterolemia (male= 69%, female= 63%), followed by central obesity (m = 41%, f = 44%), hypertension (m = 44%, f = 34%) and diabetes (m = 11%, f = 6%). At least three risk factors were present in 26% in male and 23% in female participants, while 17% of males and 22% of females had no risk factors. The prevalence and accumulation of metabolic risk factors became more common with age. Of those aged 60-69, more than 10% had all four risk factors and almost half had at least three. Central obesity increased the risk of hypertension (OR 3.11; 95% CI 2.61-3.71), diabetes (OR 3.97; 95% CI 2.86-5.52) and hypercholesterolemia (OR 1.75; 95% CI 1.48-2.07) compared to those without central obesity. Conclusions 81% of all participants had at least one metabolic risk factor for CVD and 50% had at least two. High prevalence and accumulation of CVD risk factors remains a major threat to future morbidity, mortality, and increased healthcare costs in the Finnish working-age population. It is particularly important to identify those individuals with several simultaneous risk factors. Key messages • Metabolic risk factors for CVD are common in the Finnish working-age population, with high prevalence especially hypercholesterolemia and central obesity. • If the increasing prevalence of risk factors is not addressed, morbidity, mortality and health care costs can be expected to increase in the future as the population ages.

Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US.

Emerging preclinical evidence suggests that semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA) for type 2 diabetes mellitus (T2DM) and obesity, protects against neurodegeneration and neuroinflammation. However, real-world evidence for its ability to protect against Alzheimer's disease (AD) is lacking. We conducted emulation target trials based on a nationwide database of electronic health records (EHRs) of 116 million US patients. Seven target trials were emulated among 1,094,761 eligible patients with T2DM who had no prior AD diagnosis by comparing semaglutide with seven other antidiabetic medications. First-ever diagnosis of AD occurred within a 3-year follow-up period and was examined using Cox proportional hazards and Kaplan-Meier survival analyses. Semaglutide was associated with significantly reduced risk for first-time AD diagnosis, most strongly compared with insulin (hazard ratio [HR], 0.33 [95% CI: 0.21 to 0.51]) and most weakly compared with other GLP-1RAs (HR, 0.59 [95% CI: 0.37 to 0.95]). Similar results were seen across obesity status, gender, and age groups. These findings support further studies to assess semaglutide's potential in preventing AD. Semaglutide was associated with 40% to 70% reduced risks of first-time AD diagnosis in T2DM patients compared to other antidiabetic medications, including other GLP-1RAs. Semaglutide was associated with significantly lower AD-related medication prescriptions. Similar reductions were seen across obesity status, gender, and age groups. Our findings provide real-world evidence supporting the potential clinical benefits of semaglutide in mitigating AD initiation and development in patients with T2DM. These findings support further clinical trials to assess semaglutide's potential in delaying or preventing AD.

GLP-1 analog use is associated with improved disease course in inflammatory bowel disease: a report from the Epi-IIRN.

The growing use of GLP-1 analogs for type 2 diabetes mellitus (DM2) and obesity necessitates studies about their use in patients with inflammatory bowel diseases (IBD). Data on patients with DM2 were retrieved from an Israeli nationwide cohort of patients with IBD (epi-IIRN), recording GLP-1 analog exposure for at least 6 months. Primary outcome was poor disease outcomes (i.e. composite of steroid-dependence, initiation of advanced IBD therapy, hospitalization, surgery, or death). Cox proportional hazard models with time-varying covariables were used to assess the impact of GLP-1 use on outcomes during follow-up. We included 3,737 patients (24,338 patient-years) with IBD and DM2 [(50.4% ulcerative colitis (UC)], of whom 633 were treated with GLP-1 analogs. Accounting for demographics IBD/DM2 related variables, medication use, and laboratory measurements, GLP-1 analog use was associated with reduced composite outcome in the full cohort (adjusted Hazard Ratio (aHR) 0.74, 95%CI 0.62-0.89) and in each subtype [UC (aHR 0.71, 95%CI 0.52-0.96) and Crohn's disease (aHR 0.78, 95%CI 0.62-0.99)]. Similar trends were seen in multivariate analyses of each individual outcome, although only hospitalization was significant (aHR 0.74, 95%CI 0.61-0.91). The protective effect of GLP-1 analogs was seen in patients with obesity (aHR 0.61, 95%CI 0.50-0.77), but not in non-obese (aHR 0.94, 95%CI 0.67-1.31). GLP-1 analogs are associated with improved outcomes in IBD, specifically in patients with obesity. The mechanisms of these effects require further investigation as well as their role in patients without DM2.

Neurodevelopmental Pathways to Obesity and Type 2 Diabetes: Insights From Prenatal Exposure to Maternal Obesity and Gestational Diabetes Mellitus: A Report on Research Supported by Pathway to Stop Diabetes.

Incidences of childhood obesity and type 2 diabetes (T2D) are climbing at alarming rates. Evidence points to prenatal exposures to maternal obesity and gestational diabetes mellitus (GDM) as key contributors to these upward trends. Children born to mothers with these conditions face higher risks of obesity and T2D, beyond genetic or shared environmental factors. The underpinnings of this maternal-fetal programming are complex. However, animal studies have shown that such prenatal exposures can lead to changes in brain pathways, particularly in the hypothalamus, leading to obesity and T2D later in life. This article highlights significant findings stemming from research funded by my American Diabetes Association Pathway Accelerator Award and is part of a series of Perspectives that report on research funded by the American Diabetes Association Pathway to Stop Diabetes program. This critical support, received more than a decade ago, paved the way for groundbreaking discoveries, translating the neural programming findings from animal models into human studies and exploring new avenues in maternal-fetal programming. Our BrainChild cohort includes >225 children, one-half of whom were exposed in utero to maternal GDM and one-half born to mothers without GDM. Detailed studies in this cohort, including neuroimaging and metabolic profiling, reveal that early fetal exposure to maternal GDM is linked to alterations in brain regions, including the hypothalamus. These neural changes correlate with increased energy intake and predict greater increases in BMI, indicating that early neural changes may underlie and predict later obesity and T2D, as observed in animal models. Ongoing longitudinal studies in this cohort will provide critical insights toward breaking the vicious cycle of maternal-child obesity and T2D.

The role of dietary inflammatory index in metabolic diseases: the associations, mechanisms, and treatments.

In recent years, the prevalence of metabolic diseases has increased significantly, posing a serious threat to global health. Chronic low-grade inflammation is implicated in the development of most metabolic diseases, such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia, and cardiovascular disease, serving as a link between diet and these conditions. Increasing attention has been directly toward dietary inflammatory patterns that may prevent or ameliorate metabolic diseases. The Dietary Inflammatory Index (DII) was developed to assess the inflammatory potential of dietary intake. Consequently, a growing body of research has examined the associations between the DII and the risk of several metabolic diseases. In this review, we explore the current scientific literature on the relationships between the DII, T2DM, obesity, and dyslipidemia. It summarizes recent findings and explore potential underlying mechanisms from two aspects: the interaction between diet and inflammation, and the link between inflammation and metabolic diseases. Furthermore, this review discusses the therapeutic strategies, including dietary modifications, prebiotics, and probiotics, and discusses the application of the DII in metabolic diseases, as well as future research directions.

Is Weight Loss the Most Effective Method for the Prevention of Type 2 Diabetes? A Discussion in View of Evidence from Landmark Studies

Type 2 Diabetes mellitus (T2DM) and obesity are a continuum and intertwined in a complex way. Both these chronic conditions pose a significant challenge to the global health system, if the current trend continues, it is estimated that by 2045 the number of people affected globally will increase by almost 700 million. Considering the above, effective strategies have to be implemented to tackle this global pandemic. The main strategies discussed in the literature are lifestyle intervention (ESI) with or without weight loss and medication. This article looked at the evidence from the various landmark studies which include the Diabetes Prevention Program (DPP) and Diabetes Prevention Study (DPS) Outcomes of these studies suggest that ELSI with loss is superior to ELSI without weight loss and metformin in risk reduction of T2DM. The evidence from the Swedish obese subject study also concludes that weight loss achieved through bariatric surgery reduces the risk. Lifestyle modification programmes even without weight loss have greater health benefits but as far as risk reduction for T2DM the evidence is not conclusive. This review article concludes that reducing weight is paramount for preventing T2DM, especially in high-risk individuals, compliance plays a vital role in overcoming these challenges and stresses the importance of tailored strategies for person-to-person characteristics to overcome those challenges.

The role of incretins in gestational diabetes: a case-control study on the impact of obesity

BackgroundThis study aimed to evaluate the role of serum Glucagon-Like Peptide-1 (GLP-1), Glucagon-Like Peptide-2 (GLP-2), and Glucose-Dependent Insulinotropic Polypeptide (GIP) levels in relation to obesity and gestational diabetes mellitus (GDM) in pregnancy.MethodsA case-control study was conducted, including 96 pregnant women with singleton pregnancies who underwent the Oral Glucose Tolerance Test (OGTT) for GDM diagnosis during the 24th–28th weeks of gestation. Blood samples were collected for measuring GLP-1, GLP-2, GIP, and fasting glucose. Statistical analyses included receiver operating characteristic (ROC) curves and correlation analysis.ResultsAmong the 96 women, no significant difference in age was observed between the groups, but Body Mass Index (BMI) was significantly higher in GDM-O (Gestational Diabetes Mellitus-Obese) and non-GDM-O groups (p < 0.001). GLP-1 had an area under the curve (AUC) of 0.666 (95% CI: 0.553–0.778, p = 0.005) for diagnosing GDM. The optimal GLP-1 cutoff was 815.86 ng/mL, with 65% sensitivity and 77% specificity. A significant correlation was found between GLP-2 and GIP (r = 0.289, p = 0.004), but no significant correlations were observed between GLP-1 and other peptides or gestational age (p > 0.05).ConclusionsImpaired secretion of GLP-1, GLP-2, and GIP likely contributes to the pathogenesis of GDM. GLP-1 may serve as a potential biomarker for diagnosing GDM.

Low-calorie, high-protein diets, regardless of protein source, improve glucose metabolism and cardiometabolic profiles in subjects with prediabetes or type 2 diabetes and overweight or obesity.

The aim was to study the effect of two low-calorie, high-protein (HP) diets, with most of the protein coming from animal or plant sources, on glycaemic and other cardiometabolic outcomes in subjects with overweight or obesity and glucose metabolism disorders. A total of 117 participants aged >18 years with body mass index over 27.5 kg/m2 and prediabetes or type 2 diabetes mellitus (T2DM) were randomized to one of two HP low-calorie diets (35% of total calories from protein), in which 75% of the protein was from either plant-based sources (HPP) or animal sources (HPA). For both diets, 30% and 35% of the total calories were from fat and carbohydrates, respectively. The dietary intervention lasted 6 months. Both diets improved body composition to a similar extent, including weight loss (-8.05 ± 5.12 kg for the HPA diet and -7.70 ± 5.47 kg for the HPP diet at 6 months) and fat mass, mainly visceral fat. Both diets had a similar beneficial effect on glucose metabolism, including fasting glucose, insulin, homeostasis model assessment of insulin resistance index and glycated haemoglobin. Other biochemical parameters, including lipid profiles, liver enzymes, adipokines and inflammatory biomarkers, similarly improved in both groups. Fasting incretins, mainly glucagon-like peptide 1, decreased significantly in both groups, and this effect correlated with weight loss. Low-calorie HP diets improved body composition, glucose metabolism and other cardiometabolic outcomes, regardless of protein source (either animal or plant sources), in outpatients with prediabetes or T2DM. The clinical trial was registered in ClinicalTrials.gov (identifier: NCT05456347) https://clinicaltrials.gov/study/NCT05456347?term=NCT05456347&rank=1.

From Mother to Child: Epigenetic Signatures of Hyperglycemia and Obesity during Pregnancy.

In utero exposure to maternal hyperglycemia and obesity can trigger detrimental effects in the newborn through epigenetic programming. We aimed to assess the DNA methylation levels in the promoters of MC4R and LPL genes from maternal blood, placenta, and buccal swab samples collected in children born to mothers with and without obesity and Gestational Diabetes Mellitus (GDM). A total of 101 Caucasian mother-infant pairs were included in this study. Sociodemographic characteristics, clinical parameters, physical activity, and adherence to the Mediterranean diet were evaluated in the third trimester of pregnancy. Clinical parameters of the newborns were recorded at birth. A negative relationship between MC4R DNA methylation on the fetal side of the GDM placenta and birth weight (r = -0.630, p = 0.011) of newborns was found. MC4R DNA methylation level was lower in newborns of GDM women (CpG1: 2.8% ± 3.0%, CpG2: 3.8% ± 3.3%) as compared to those of mothers without GDM (CpG1: 6.9% ± 6.2%, CpG2: 6.8% ± 5.6%; p < 0.001 and p = 0.0033, respectively), and it was negatively correlated with weight (r = -0.229; p = 0.035), head circumference (r = -0.236; p = 0.030), and length (r = -0.240; p = 0.027) at birth. LPL DNA methylation was higher on the fetal side of the placenta in obese patients as compared to normal-weight patients (66.0% ± 14.4% vs. 55.7% ± 15.2%, p = 0.037), and it was associated with maternal total cholesterol (r = 0.770, p = 0.015) and LDL-c (r = 0.783, p = 0.012). These results support the role of maternal MC4R and LPL methylation in fetal programming and in the future metabolic health of children.

Serial Liver Stiffness Measurement and Fibrosis-4 Scores in Metabolic Dysfunction-Associated Steatotic Liver Disease.

In patients with metabolic dysfunction-associated steatotic liver disease (MASLD), there are limited data on how changes in FIB4 and liver stiffness measurement (LSM) correlate in non-biopsy cohorts. Our objective was to evaluate associations between changes in FIB4 and LSM in MASLD patients. We included MASLD patients with serial VCTE from 2015-2022. The primary predictors were change in FIB4 and presence of diabetes, obesity, and high alanine aminotransferase (ALT). The primary outcome, applied only to patients with LSM1 < 8kPa, was incident significant fibrosis (SF) defined as a ≥ 20% increase in LSM2 vs. LSM1 and LSM2 ≥ 8kPa. A secondary outcome was LSM progression with a similar definition but applied to all participants, not only those with LSM1 < 8kPa. Of 285 included patients, 216 had LSM1 < 8kPa and were included in the primary analysis; of these, 34 (16%) had incident SF. Changes in FIB4 correlated with changes in LSM (R = 0.16, p = 0.016). Independent predictors of incident SF included comorbid diabetes mellitus (OR 2.43, 95% CI 1.04-6.56), obesity (OR 3.88, 95% CI 1.63-9.25), and baseline ALT ≥ 30 (OR 8.55, 95% CI 1.10-66.29). A model including ALT, diabetes, and obesity outperformed a model with FIB4 change alone. Among patients with MASLD, changes in FIB4 correlated with changes in LSM but more significant correlates of incident significant fibrosis included diabetes mellitus, obesity, and high baseline ALT.

Addressing Obesity in Diabetes

Addressing Obesity in Diabetes

Pre-pregnancy and gestational interventions to prevent childhood obesity.

Childhood obesity is a significant global health issue with complex and multifactorial origins, often beginning before conception and influenced by both maternal and paternal health. The increased prevalence of pre-pregnancy obesity and gestational diabetes mellitus in women of reproductive age contributes to a heightened risk of metabolic dysfunction in offspring. Current clinical practices often implement lifestyle interventions after the first trimester, and have limited success, implying that they miss a critical window for effective metabolic adjustments. This review examines the limitations of lifestyle interventions during pregnancy in improving perinatal outcomes and highlights the importance of initiating such interventions before conception to positively impact parental health and fetal development. A re-evaluation of strategies is needed to enhance the metabolic health of prospective parents as a preventive measure against childhood obesity.

Prenatal maternal diabetes, comorbidities, and risk for neurodevelopmental impairment in the first two years.

Maternal diabetes is a known risk for neurodevelopmental delay in offspring, and often presents with comorbid metabolic conditions, such as obesity and hypertension. However, their combined effects on neurodevelopmental outcomes remain unclear. We investigated the independent and combined associations of maternal diabetes and comorbidities with the risk of neurodevelopmental delay in children aged 12 and 24 months. A prospective longitudinal cohort of children from Pregnancy during the COVID-19 Pandemic study. Neurodevelopmental screening at 12 and 24 months was conducted using the Ages and Stages Questionnaire, which assesses domain-specific development. Maternal diabetes was not associated with neurodevelopmental risks either at 12 or 24 months. However, in combined analyses, maternal diabetes and pre-pregnancy overweight were associated with an increased risk of neurodevelopmental delay in personal-social skills (odds ratio [OR], 1.75 [95%CI,1.01-3.01]) at 24 months, though not at 12 months. Maternal diabetes and pre-pregnancy obesity were also associated with an increased risk for neurodevelopmental delay in communication (OR, 1.71 [95%CI,1.01-2.82]) and personal-social skills (OR, 2.01 [95%CI,1.03-3.73]) at 24 months. Furthermore, maternal diabetes and hypertensive disorders of pregnancy (HDP) had higher rates of positive screening for delay in fine-motor skills (OR, 3.54 [95%CI, 1.28-8.41]) at 12 months but not at 24 months. Post-hoc analysis revealed an independent association of maternal pre-pregnancy obesity, but not overweight, with an increased risk of neurodevelopmental delay in communication, fine-motor, and personal-social skills (ORs ranging from 1.44 to 1.71) at 24 months but not 12 months. Similarly, there was an independent association of maternal HDP with an increased risk of neurodevelopmental delay in fine-motor and and personal-social skills (ORs ranging from 2.01 to 2.19) at 24 months. Maternal diabetes with comorbid conditions is likely to increase the risk of neurodevelopmental delay during infancy than individual exposure, suggesting the persistent influence of prenatal exposure on offspring neurodevelopment. 1. Identifying modifiable prenatal risk factors for neurodevelopmental impairment in offspring is crucial for targeted interventions and providing support to mothers during pregnancy, which can lead to improved child health outcomes. 2. Maternal diabetes was not associated with neurodevelopmental delays in children at 12 or 24 months. 3. Maternal diabetes in combination with pre-pregnancy overweight or obesity increased the risk of cognitive delay at 24 months. 4. Maternal pre-pregnancy obesity but not overweight, and hypertensive disorders of pregnancy independently increased risks of cognitive and motor delays at 24 months.

Akkermansia muciniphila for the Prevention of Type 2 Diabetes and Obesity: A Meta-Analysis of Animal Studies.

More than half of the states in the U.S. report that over 30% of adults are obese. Obesity increases the risk of many chronic diseases, including type 2 diabetes, hypertension, and cardiovascular disease, and can even reduce one's lifespan. Similarly, the prevalence of type 2 diabetes follows a comparable trend. As a result, researchers are striving to find solutions to reduce obesity rates, with a particular focus on gut health, which has been previously linked to both obesity and type 2 diabetes. Recent studies suggest that Akkermansia muciniphila (Akk) may have a positive probiotic effect on preventing the onset of type 2 diabetes and obesity. We conducted a quantitative meta-analysis of 15 qualified animal studies investigating the effects of Akk administration as a probiotic. The statistical analyses showed that Akk administration significantly reduced body weight gain by 10.4% and fasting blood glucose by 21.2%, while also significantly improving glucose tolerance by 22.1% and increasing blood insulin levels by 26.9%. However, our analysis revealed substantial heterogeneity between the control and experimental groups across all subgroups. Overall, Akk appears to be effective at reducing the onset of type 2 diabetes and diet-induced obesity. Long-term studies with larger sample sizes are needed to confirm these beneficial effects, as the current animal studies were of short duration (less than 20 weeks).

Ameliorative effects of Penthorum chinense Pursh on insulin resistance and oxidative stress in diabetic obesity db/db mice.

Penthorum chinense Pursh (PCP), a medicinal and edible plant, has been reported to protect against liver damage by suppressing oxidative stress. Type 2 diabetes mellitus (T2DM) is associated with liver dysfunction and oxidative stress. In the present study, we aim to investigate the hypoglycemic effect of PCP on db/db mice and further explore the underlying mechanisms. Thirty-two db/db mice were randomized into four groups, including a diabetic model control group (MC) and three diabetic groups treated with low (LPCP, 300 mg/kg/d), medium (MPLP, 600 mg/kg/d), and high doses of PCP (HPCP, 1200 mg/kg/d), and the normal control group (NC) of eight db/m mice were included. Mice in the NC and MC groups received the ultrapure water. After four weeks of intervention, parameters of fasting blood glucose (FBG), insulin resistance (IR), blood lipid levels, hepatic oxidative stress, and enzymes related to hepatic glucose metabolism were compared in the groups. PCP administration significantly reduced FBG and IR in diabetic db/db mice, and improved hepatic glucose metabolism by increasing glucose transporter 2 (GLUT2) and glucokinase (GCK) protein expression. Meanwhile, PCP supplementation ameliorated hepatic oxidative stress by decreasing malonaldehyde content and increasing the activities of superoxide dismutase and glutathione peroxidase in db/db mice. Furthermore, PCP treatment reduced obesity and food intake in db/db mice, and improved dyslipidemia demonstrated by increasing high-density lipoprotein cholesterol (HDL-C) while decreasing total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (HDL-C). All doses of PCP treatment decreased the values of LDL-C/HDL-C in a dose-response relationship. PCP significantly alleviated hyperglycemia, hyperinsulinemia, hyperlipidemia, and obesity, inhibited hepatic oxidative stress, and enhanced hepatic glucose transport in T2DM mice. Based on the above findings, the hypoglycemic effect of PCP may be attributed to the activation of the GLUT2/GCK expression in the liver and the reduction of hepatic oxidative stress.