Obese Non-diabetic Patients Research Articles

Risk-stratified hepatocellular carcinoma screening according to the degree of obesity and progression to cirrhosis for diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD) in Japan: a cost-effectiveness study.

To evaluate the cost-effectiveness of risk-stratified hepatocellular carcinoma (HCC) screening in diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD). A state-transition model from a healthcare payer perspective on a lifetime horizon. Japan. A hypothetical cohort of 50-year-old diabetic patients with MASLD risk-stratified according to degree of obesity and progression to cirrhosis. Metabolic dysfunction-associated steatotic liver (MASL), metabolic dysfunction-associated steatohepatitis (MASH) and MASH cirrhosis are progressive manifestations of this specific type of liver disease. Abdominal ultrasound (US), US with alpha-fetoprotein (AFP), US with AFP and lectin-reactive alpha-fetoprotein (AFP-L3), CT, extracellular contrast-media-enhanced MRI (ECCM-MRI), gadoxetic acid-enhanced MRI (EOB-MRI) and no screening. Costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), early-stage HCC cases, advanced-stage HCC cases and HCC-related deaths. EOB-MRI is the most cost-effective screening method for non-obese diabetic patients with MASH cirrhosis and for obese diabetic patients with MASH and MASH cirrhosis. Cost-effectiveness was sensitive to HCC incidence in non-obese diabetic patients with MASH cirrhosis and obese diabetic patients with MASH, and the adherence rate of HCC screening in obese diabetic patients with MASH. When the semiannual HCC incidence was between 0.008 and 0.0138 in non-obese diabetic patients with MASH cirrhosis, US with AFP was more cost-effective than EOB-MRI. Cost-effectiveness acceptability curves showed that EOB-MRI was 50.7%, 96.0% and 99.9% cost-effective in obese diabetic patients with MASH and non-obese diabetic patients with MASH cirrhosis, and obese diabetic patients with MASH cirrhosis at a willingness-to-pay level of $50 000 per QALY gained. Compared with no screening in 100 000 non-obese diabetic patients with MASH cirrhosis and obese diabetic patients with MASH cirrhosis, EOB-MRI reduced total costs by US$69 million and by US$142 million, increased lifetime effectiveness by 12 546 QALYs and by 15 815 QALYs, detected 17 873 and 21 014 early-stage HCC cases, and averted 2068 and 2471 HCC-related deaths, respectively. Of all HCC screening methods for diabetic patients with MASH cirrhosis, EOB-MRI yields the greatest cost-saving with the highest QALYs, detects the greatest number of early-stage HCC cases and averts the greatest number of advanced-stage HCC cases and HCC-related deaths. The findings provide important insights for the precise implementation of risk-stratified HCC surveillance to reduce morbidity and mortality and improve the quality of life in diabetic patients with MASLD.

Assessment of Left Arterial Function by using 2-Dimensional Speckle Tracking in Obese versus Non-Obese Diabetic Patients

Both obesity and diabetes are major problems for the public's health. Both are known to contribute to the development of atrial cardiomyopathy. However, the consequences of obesity on the function of the left atrium(LA) in diabetic individuals have not been determined as of yet. The aim of this study is to compare the peak atrial longitudinal strain (PALS) measured by two-dimensional (2D) speckle tracking in obese versus non-obese diabetic Iraqi patients. For a study that was designed to be cross-sectional, the data collection period lasted for a total of ten months. In this study, the participants had to have diabetes mellitus type 2. A comparison was made between patients who were obese and patients who were not obese using 2-D speckle tracking to measure the peak left atrial longitudinal strain. Several additional factors, such as age, gender, body mass index, conventional echocardiographic parameters, and volume-derived LA function, were investigated during this study. A total of 59 patients participated in this study. The ratio of males to females was exactly 1:1.5, and the average age was (54 ± 9.4) years old. Coexistent systemic arterial hypertension was observed in 25 % of the study population. Patients with type 2 diabetes mellitus and obesity had ad higher E/e` ratio and lower PALS than patients with type 2 diabetes mellitus without obesity, whereas all other parameters were statistically non-significant (EF, E/A, S prime, LA volume index). It was found that the peak longitudinal strain of the LA, which was measured using 2-D speckle tracking, was lower in the obese diabetic individuals. This was in contrast to diabetic people, who did not have obesity issues. An evaluation of the global strain in the left atrium can help in the early detection of remodeling and dysfunction in the left atrium if it is compared to the size of the left atrium and the filling pressures of the left ventricle, both of which are respectively determined by the E/e' ratio and the left atrial volume.

Correlations between serum Afamin, retinol binding protein-4 and plasminogen activator inhibitor-1 in obese diabetic and non-diabetic patients

Correlations between serum Afamin, retinol binding protein-4 and plasminogen activator inhibitor-1 in obese diabetic and non-diabetic patients

SELECT: Glucagon-like peptide-1 receptor agonist in obese patients with cardiovascular disease in the absence of diabetes.

Obesity is a global epidemic affecting 2.5 billion people and is recognized as the fourth leading cause of global mortality. Obesity is characterized by excessive accumulation of body fat and is associated with a range of health consequences, including an elevated risk of cardiovascular disease (CVD). Glucagon-like peptide-1 (GLP-1) receptor agonists have been proven to reduce cardiovascular outcomes in patients with diabetes. Study and results: The SELECT trial was a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, conducted at 804 clinical sites in 41 countries. Patients were randomly assigned in a 1:1 ratio, to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. The primary cardiovascular efficacy endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-first-event analysis. A total of 17,604 patients were recruited, with a mean age of 61.6 years and 72.3% males. The mean duration of exposure to semaglutide or placebo in the overall trial population was 34.2±13.7 months. The primary CVD endpoint occurred in 6.5% (n=569) of the semaglutide group and 8% (n=701) in the placebo group (hazard ratio, 0.80; 95% CI, 0.72 to 0.90; P<0.001). There was also a significant reduction of 9.39% in body weight among the patients taking semaglutide over 104 weeks after randomization versus 0.88% among the placebo group. Semaglutide reduces the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in obese and overweight non-diabetic patients with preexisting cardiovascular disease.

PREX proteins level correlation with insulin resistance markers and lipid profile in obese and overweight non-diabetic patients

Metabolic dysregulation and obesity are associated with many metabolic alterations, including impairment of insulin sensitivity and dyslipidemia. Recent studies highlight the key role of phosphatidylinositol 3,4,5-triphosphate-dependent Rac exchange proteins (PREX proteins) in the pathogenesis of obesity, advocating further elucidation of their potential therapeutic implications. The present study aimed to estimate the serum level of PREX proteins and its potential association with insulin resistance markers and plasma lipids level in obese and overweight non-diabetic patients. The study included 30 persons classified as obese, 30 as overweight, and 30 healthy individuals of similar age and gender. The levels of PREX1 and PREX2 were measured using ELISA kits, insulin, fasting glucose, glycosylated hemoglobin and total lipid profile were determined using appropriate photometric kits. HOMA-IR was used as a measure of insulin sensitivity. According to the obtained results, obese non-diabetic patients had higher serum PREX1 level compared to both overweight and normal-weight individuals. PREX1 correlated positively with the markers of insulin resistance and dyslipidemia. PREX2 level was shown to be lower both in obese compared to overweight patients and in overweight compared to normal-weight individuals. PREX2 correlated negatively with the markers of insulin resistance but not with the markers of dyslipidemia. Keywords: dyslipidemia, insulin resistance, obesity, overweight, PREX proteins

The Five-Year Incidence of Progression to Osteoarthritis and Total Joint Arthroplasty in Patients Prescribed Glucagon-Like Peptide 1 Receptor Agonists

BackgroundResearch has suggested that glucagon-like peptide-1 receptor agonists (GLP-1-RAs) may have therapeutic effects on osteoarthritis of the hip and knee, in addition to managing diabetes and obesity. However, there is a lack of understanding regarding the association between GLP-1-RA use and the diagnosis of osteoarthritis (OA) of the hip and knee. MethodsA collaborative network analytics platform was queried for obese diabetic (n = 1,094,198), obese nondiabetic (n = 916,235), and nonobese diabetic (n = 157,305) patients who had an index visit between 2015 and 2017. Patients who had pre-existing hip and/or knee OA were excluded. A 1:1 propensity score matching was used to balance GLP-1-RA use in stratified cohorts for age, sex, race, body mass index, and hemoglobin A1c. The primary outcomes were rates of progression to hip OA, knee OA, major joint injections, total hip arthroplasty, and total knee arthroplasty. Cox proportional hazards models determined hazard ratios (HRs) between cohorts prescribed and not prescribed GLP-1-RAs. ResultsAll patients had a five-year follow-up. Rates of progression to hip and knee OA were higher among the GLP-1-RA users in both obese diabetic (hip HR: 1.63, 95% confidence interval [CI]: 1.46 to 1.82; knee HR: 1.52, CI: 1.41 to 1.64) and nonobese diabetic (hip HR: 1.78, CI: 1.50 to 2.10; knee HR: 1.58, CI: 1.39 to 1.80) cohorts. These diabetic cohorts received higher rates of major joint injections, though there was no difference in rates of total hip arthroplasty or total knee arthroplasty. No differences in five-year outcomes were seen when comparing obese, nondiabetic patients who were prescribed GLP-1-RAs with obese, nondiabetic patients not exposed to GLP-1-RAs. ConclusionsThis five-year analysis found a greater risk of progression to hip and knee OA among obese and non-obese diabetic GLP-1-RA users. Further studies should explore GLP-1-RA effects upon glucose management, weight loss, and lower extremity arthritis development. Level of EvidenceIII, retrospective cohort study.

Associations between Serum Kallistatin Levels and Markers of Glucose Homeostasis, Inflammation, and Lipoprotein Metabolism in Patients with Type 2 Diabetes and Nondiabetic Obesity.

Kallistatin is an endogenous serine proteinase inhibitor with various functions, including antioxidative, anti-inflammatory, and anti-atherosclerotic properties. To date, associations between kallistatin and lipoprotein subfractions are poorly investigated. In this study, we enrolled 62 obese patients with type 2 diabetes (T2D), 106 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index, as well as 49 gender- and age-matched healthy, normal-weight controls. Serum kallistatin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint® (Quantimetrix Corp., Redondo Beach, CA, USA) gel electrophoresis. Kallistatin concentrations were significantly higher in T2D patients compared to NDO and control groups. We found significant positive correlations between very-low-density lipoprotein (VLDL), small high-density lipoprotein (HDL) subfractions, glucose, hemoglobin A1c (HbA1c), betatrophin, and kallistatin, while negative correlations were detected between mean low-density lipoprotein (LDL) size, large and intermediate HDL subfractions, and kallistatin in the whole study population. The best predictor of kallistatin was HbA1c in T2D patients, high-sensitivity C-reactive protein (hsCRP) and betatrophin in NDO patients, and hsCRP in controls. Our results indicate that kallistatin expression might be induced by persistent hyperglycemia in T2D, while in nondiabetic subjects, its production might be associated with systemic inflammation. The correlation of kallistatin with lipid subfractions may suggest its putative role in atherogenesis.

Improvement of non-alcoholic steatohepatitis as measured by elastography in obese diabetic and non-diabetic patients undergoing bariatric surgery, after one-year follow-up

Improvement of non-alcoholic steatohepatitis as measured by elastography in obese diabetic and non-diabetic patients undergoing bariatric surgery, after one-year follow-up

Vitamin D status and steatohepatitis in obese diabetic and non-diabetic patients

Vitamin D status and steatohepatitis in obese diabetic and non-diabetic patients

Tirzepatide-Induced Ketoacidosis in Non-Diabetic Patients.

Tirzepatide is a novel glucagon-like peptide 1/glucose-dependent insulinotropic peptide (GLP-1/GIP) receptor agonist. It was recently approved for diabetes control and weight reduction in non-diabetic patients. We report the first case of ketoacidosis after the use of tirzepatide in an obese non-diabetic patient, secondary to the possibility of starvation ketoacidosis and insulin resistance. The dual-acting GLP-1 and GIP receptor agonists, tirzepatide, can induce ketoacidosis in obese non-diabetic patients. The dual-acting GLP-1 and GIP receptor agonists can cause ketoacidosis in obese non-diabetic patients.Ketoacidosis induced by tirzepatide is serious, and physicians should be aware of this complication and be alert to early symptoms, check serum and urine ketone levels, and stop medication.

The impact of metformin on weight and metabolic parameters in patients with obesity: A systematic review and meta-analysis of randomized controlled trials.

There are conflicting data on the weight-reducing potential of metformin (MTF) in nondiabetic patients with obesity. The purpose of this systematic review and meta-analysis was to evaluate the effect of MTF on weight and cardiometabolic parameters in adults with overweight/obesity with or without nonalcoholic fatty liver disease (NAFLD) (CRD42018085512). We included randomized controlled trials (RCTs) in adults without diabetes mellitus, with mean body mass index (BMI) ≥ 25 kg/m2, with or without NAFLD, comparing MTF to placebo/control, lifestyle modification (LSM) or a US Food and Drug Administration-approved anti-obesity drug, reporting on weight or metabolic parameters, and extending over at least 3 months. We conducted a systematic search in MEDLINE, EMBASE, PubMed and the Cochrane Library without time limitation (until March 2022). We screened and selected eligible articles, abstracted relevant data, and assessed the risk of bias. All steps were in duplicate and independently. We conducted a random-effects model meta-analysis using Review Manager version 5.3, with prespecified subgroup analyses in case of heterogeneity. We identified 2650 citations and included 49 trials (55 publications). Compared to placebo, MTF was associated with a significant reduction in BMI (mean difference [MD] -0.56 [-0.74, -0.37] kg/m2; p < 0.0001), at doses ranging from 500 to 2550 mg/day, and with a significant percentage change in BMI of -2.53% (-2.90, -2.17) at the dose 1700 mg/day. There was no interaction by baseline BMI, MTF dose or duration, nor presence or absence of NAFLD. There was no significant difference between MTF and LSM. Orlistat was more effective than MTF (at doses of 1000-1700 mg/day) in terms of weight loss, with an MD in BMI of -3.17 (-5.88; -0.47) kg/m2, favouring the former. Compared to placebo/control, MTF improved insulin parameters, while no effect was detected when compared to LSM. A few small trials showed heterogenous effects on liver parameters in patients with NAFLD treated with MTF compared to placebo/control. There was a large variability in the expression of outcome measures and RCTs were of low quality. In conclusion, MTF was associated with a modest weight reduction in obese nondiabetic patients. Further high-quality and better powered studies are needed to examine the impact of MTF in patients with insulin resistance and NAFLD.

Genetic Investigation of the Trail Mechanism in Diabetic and Non-diabetic Obese Patients.

Obesity is an important healthcare issue caused by abnormally increased adipose tissue because of energy-intake overcoming energy expenditure. Disturbances in the physiological function of adipose tissue mediate the development of diabetes. It is a metabolic disease that results from decreased insulin-levels and/or changes in the insulin action mechanism. Tumor Necrosis Factor-Associated Apoptosis-Inducing Ligand(TRAIL), which is a member of the Tumor Necrosis Factor(TNF)-family with an important role in adipose tissue biology, is included in many studies with its ability to induce apoptosis in cancer cells, but the number of human-studies conducted on the gene related to its protective-role against diabetes and obesity at this level is insufficient. Our study was carried out as a case and control and included three groups (80 diabetic obese, 80 non-diabetic obese, and 80 healthy individuals as the control group). The Real-Time-PZR(RT-qPZR), and DNA Sanger-Sequencing Methods were used for gene expression and gene squences. As a result of the analyses, TRAIL gene expression level was found to be higher in the controls than in the diabetic-obese and non-diabetic-obese group. This change in TRAIL gene expression suggests that TRAIL maybe a protective factor against diabetes. The presence of rs781673405, rs143353036, rs1244378045, rs767450259, rs759369504, rs750556128, and rs369143448 mutations, which was determined with the Sequencing-Method, was shown for the first time in the present study. In addition, it is the first study in which human TRAIL gene-expression and sequencing were performed together. We believe that these data will make an important contribution to the literature.

Metabolomic signature between diabetic and non-diabetic obese patients: A protocol for systematic review.

Type 2 diabetes mellitus (T2DM) is a chronic and progressive condition defined by hyperglycemia caused by abnormalities in insulin production, insulin receptor sensitivity, or both. Several studies have revealed that higher body mass index (BMI) is associated with increasing risk of developing diabetes. In this study, we perform a protocol for systematic review to explore metabolite biomarkers that could be used to identify T2DM in obese subjects. The protocol of this review was registered in PROSPERO (CRD42023405518). Three databases, EMBASE, PubMed, and Web of Science were selected to collect potential literature from their inceptions to July December 2023. Data for collection will include title, authors, study subjects, publication date, sample size, detection and analytical platforms, participant characteristics, biological samples, confounding factors, methods of statistical analysis, the frequency and directions of changes in potential metabolic biomarkers, and major findings. Pathway analysis of differential metabolites will be performed with MetaboAnalyst 5.0 based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Human Metabolome Database. The results of this systematic review will be published in a peer-reviewed journal. This systematic review will summarize the potential biomarkers and metabolic pathways to provide a new reference for the prevention and treatment of T2DM in obese subjects.

ADIPOPHILIN PEPTIDE (ADPH 129-137) IS NOT A TARGET ANTIGEN FOR CD8+ T-CELLS IN PATIENTS WITH OBESITY.

In obesity, the infiltration of leukocytes into adipose tissue seems to play a key role in the development of inflammation and insulin resistance. Over-expression of adipophilin (ADPH) in adipose tissue, a protein which regulates lipid droplet structure and formation, has been reported in some studies. To investigate the role of ADPH 129-137 as a target for CD8+ T-cells in PBMCs of patients with obesity. PBMCs were obtained from 9 non-diabetic obese patients and 11 healthy subjects expressing the HLA-A0201 molecule. The ELISPOT assay used to monitor the presence of IFN-γ producing CD8+ T-cells against a HLA class I-restricted epitope derived from Adipophilin (ADPH 129-137) and two control peptides: Flu MP58-66 and Melan-A27-35. The outcomes showed no significant difference between patient group and healthy donors in response to ADPH 129-137. These results demonstrated that ADPH 129-137 peptide possibly does not act as an autoantigen in patients with obesity.

Comparison of glucagon-like peptide-1 receptor agonists vs. placebo on any cardiovascular events in overweight or obese non-diabetic patients: a systematic review and meta-analysis.

Glucagon-like peptide 1 receptor agonists (GLP-1 RA) have been extensively used to treat obesity in recent years. These novel drugs are effective at reducing body weight and also the risk of major adverse cardiovascular events in individuals with type 2 diabetes. However, the data of its efficacy in reducing cardiovascular events in individuals without type 2 diabetes is not as robust. We aim to update and conduct a systematic review and meta-analysis to assess the same. The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guideline. Researchers searched PubMed, EMBASE, and Clinicaltrails.gov for English literature from inception to 2024. Randomized Controlled trails enrolling adult participants (age ≥ 18 years) who are overweight or obese (BMI > 25 Kg/m2) with a comparison of all cardiovascular events between patients taking GLP1-RA and placebo were included. The analysis was done by Revman version 5.4. A total of 17 RCTs among 34,419 participants were included in the analysis. The pooled risk ratio from 17 studies illustrated that patients with GLP-1 RA had a significantly lower risk of cardiovascular events compared to patients who had a placebo (RR = 0.75; 95% confidence interval 0.64-0.89, p-value = 0.0008). Semaglutide was found to have a statistically significant greatest risk reduction than other drug types. This meta-analysis found that GLP-1 RA significantly reduced all types of cardiovascular events in overweight and obese patients without diabetes. Semaglutide was found to be superior to others in CV event reductions. But still, the results of ongoing trials are needed. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=553048, PROSPERO (CRD42024553048).

HAMSAB diet ameliorates dysfunctional signaling in pancreatic islets in autoimmune diabetes

An altered gut microbiota is associated with type 1 diabetes (T1D), affecting the production of short-chain fatty acids (SCFA) and glucose homeostasis. We previously demonstrated that enhancing serum acetate and butyrate using a dietary supplement (HAMSAB) improved glycemia in non-obese diabetic (NOD) mice and patients with established T1D. The effects of SCFA on immune-infiltrated islet cells remain to be clarified. Here, we performed single-cell RNA sequencing on islet cells from NOD mice fed an HAMSAB or control diet. HAMSAB induced a regulatory gene expression profile in pancreas-infiltrated immune cells. Moreover, HAMSAB maintained the expression of β-cell functional genes and decreased cellular stress. HAMSAB-fed mice showed preserved pancreatic endocrine cell identity, evaluated by decreased numbers of poly-hormonal cells. Finally, SCFA increased insulin levels in human β-like cells and improved transplantation outcome in NOD/SCID mice. Our findings support the use of metabolite-based diet as attractive approach to improve glucose control in T1D.

Gender-Dependent Associations between Serum Betatrophin Levels and Lipoprotein Subfractions in Diabetic and Nondiabetic Obese Patients.

Betatrophin, also known as angiopoietin-like protein 8 (ANGPTL8), mainly plays a role in lipid metabolism. To date, associations between betatrophin and lipoprotein subfractions are poorly investigated. For this study, 50 obese patients with type 2 diabetes (T2D) and 70 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index (BMI) as well as 49 gender- and age-matched healthy, normal-weight controls were enrolled. Serum betatrophin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint gel electrophoresis. Betatrophin concentrations were found to be significantly higher in the T2D and NDO groups compared to the controls in all subjects and in females, but not in males. We found significant positive correlations between triglyceride, very low density lipoprotein (VLDL), large LDL (low density lipoprotein), small LDL, high density lipoprotein (HDL) -6-10 subfractions, and betatrophin, while negative correlations were detected between betatrophin and IDL, mean LDL size, and HDL-1-5. Proportion of small HDL was the best predictor of betatrophin in all subjects. Small LDL and large HDL subfractions were found to be the best predictors in females, while in males, VLDL was found to be the best predictor of betatrophin. Our results underline the significance of serum betatrophin measurement in the cardiovascular risk assessment of obese patients with and without T2D, but gender differences might be taken into consideration.

Evaluation Of Lipid Profile, and Preptin Between Obese Non-Diabetic Patients and Women with Polycystic Ovary Syndrome in Al Diwaniyah, Iraq

Evaluation Of Lipid Profile, and Preptin Between Obese Non-Diabetic Patients and Women with Polycystic Ovary Syndrome in Al Diwaniyah, Iraq

Plasma Adiponectin and Its Correlation with Carotid Intima-Media Thickness in Obesity and in Type 2 Diabetes and Nonalcoholic Fatty Liver Disease.

The study included 200 Egyptian subjects. They were divided into four equal groups: group 1: obese patients with NAFLD and T2DM (O+/NAFLD+/DM+), group 2: nonobese patients with NAFLD and T2DM (O-/NAFLD+/DM+), group 3: obese nondiabetic patients with NAFLD (O+/NAFLD+/DM-), and group 4: nonobese healthy control subjects. Plasma adiponectin was measured using ELISA (enzyme-linked immunosorbent assay) technique. Ultrasonography was used to diagnose NAFLD. CIMT was assessed using Doppler ultrasonography. Plasma adiponectin was significantly lower and CIMT was significantly higher in O+/NAFLD+/DM+, as compared with O-/NAFLD+/DM+, O+/NAFLD+/DM-, and control subjects (p < 0.001 for all). A significant negative correlation was found between adiponectin and CIMT in obese patients with NAFLD (p < 0.05), but not in patients with NAFLD and T2DM. The significant independent predictors of CIMT were diabetes duration, BMI (body mass index), albumin/creatinine ratio, and cholesterol. Plasma adiponectin is inversely correlated with CIMT in obese patients with NAFLD, but not in patients with NAFLD and T2DM. Hypoadiponectinemia could be a good indicator of cardiovascular risk in obese patients with NAFLD, with or without T2DM, but not in nonobese patients with NAFLD.

Nanotargeted Delivery of Immune Therapeutics in Type 1 Diabetes.

Immune therapeutics holds great promise in the treatment of type 1 diabetes (T1D). Nonetheless, their progress is hampered by limited efficacy, equipoise, or issues of safety. To address this, a novel and specific nanodelivery platform for T1D that targets high endothelial venules (HEVs) presented in the pancreatic lymph nodes (PLNs) and pancreas is developed. Data indicate that the pancreata of nonobese diabetic (NOD) mice and patients with T1D are unique in their expression of newly formed HEVs. Anti-CD3 mAb is encapsulated in poly(lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles (NPs), the surfaces of which are conjugated with MECA79 mAb that recognizes HEVs. Targeted delivery of these NPs improves accumulation of anti-CD3 mAb in both the PLNs and pancreata of NOD mice. Treatment of hyperglycemic NOD mice with MECA79-anti-CD3-NPs results in significant reversal of T1D compared to those that are untreated, treated with empty NPs, or provided free anti-CD3. This effect is associated with a significant reduction of T effector cell populations in the PLNs and a decreased production of pro-inflammatory cytokine in the mice treated with MECA79-anti-CD3-NPs. In summary, HEV-targeted therapeutics may be used as a means by which immune therapeutics can be delivered to PLNs and pancreata to suppress autoimmune diabetes effectively.