Management of acute kidney disease in type 2 diabetes: the potential role of GLP-1 RAs and SGLT2-Is.

Acute kidney disease (AKD) is defined as subacute damage and/or loss of kidney function occurring 7 to 90 days after acute kidney injury (AKI), and bearing a high risk of progression to chronic kidney disease. Current management of AKD is non-specific and includes prevention of repeated AKI, early and regular follow-up by a nephrologist, resumption and dose adjustment of statins and renin-angiotensin system inhibitors, optimization of blood pressure control, nutrition management, and nephrotoxin avoidance. Recently, SGLT2i and GLP1- RAs have emerged as potential therapeutic tools preventing the transition from acute to chronic kidney disease due to their efficacy in preserving renal function.

Finerenone's Impact on Major Adverse Cardiovascular Events in Chronic Kidney Disease and Type 2 Diabetes Mellitus: A Systematic Review.

Chronic kidney disease (CKD) impacts about 10% of adults globally and substantially elevates the risk of major adverse cardiovascular events (MACE), such as heart attacks, strokes, cardiovascular-related deaths, and hospital admissions due to heart failure. The interplay between CKD and cardiovascular disease (CVD) leads to poor health outcomes. Nevertheless, there is a scarcity of systematic reviews focusing on the effectiveness of finerenone, a new non-steroidal mineralocorticoid receptor antagonist (MRA), in lowering these risks. In this systematic review, we aim to evaluate the impact of finerenone on reducing MACE in individuals with CKD and type 2 diabetes mellitus (T2DM). CKD pathophysiology involves hyperglycemia, hypertension, and dyslipidemia, leading to glomerular hyperfiltration, inflammation, and fibrosis. Traditional treatments, including angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i), often fall short in preventing cardiovascular events. Steroidal MRAs like spironolactone and eplerenone, while effective in reducing proteinuria, are limited by hyperkalemia risks. Finerenone offers a more selective mechanism, reducing sodium retention, inflammation, and fibrosis, with a lower risk of hyperkalemia. We searched five electronic databases comprehensively, identifying studies consistently demonstrating that finerenone significantly reduces MACE and improves renal outcomes by reducing albuminuria and slowing the fall in estimated glomerular filtration rate (eGFR). However, limitations include study heterogeneity, short follow-up periods, and potential publication bias. In conclusion, finerenone shows promise as a therapeutic option for CKD and T2DM, reducing MACE and improving renal outcomes. Further research is needed to understand its long-term benefits and safety across diverse populations.

High-intensity interval training reduces Tau and beta-amyloid accumulation by improving lactate-dependent mitophagy in rats with type 2 diabetes.

Objectives: This study aimed to investigate the effect of 8-week high-intensity interval training (HIIT) on lactate-induced mitophagy in the hippocampus of rats with type 2 diabetes. Materials and Methods: 28 Wistar male rats were divided into four groups randomly: (i) control (Co), (ii) exercise (EX), (iii) type 2 diabetes (T2D), and (iv) type 2 diabetes + exercise (T2D + Ex). The rats in the T2D and T2D + Ex groups were fed a high-fat diet for two months, then a single dose of STZ (35 mg/kg) was injected to induce diabetes. The EX and T2D + Ex groups performed 4-10 intervals of treadmill running at 80-100% of Vmax. Serum and hippocampal levels of lactate, as well as hippocampal levels of monocarboxylate transporter2 (MCT2), sirtuin1 (SIRT1), forkhead box protein O (FOXO3), light chain 3 (LC3), PTEN-induced kinase 1 (PINK1), parkin, beta-amyloid (Aß), hyperphosphorylated tau protein (TAU), Malondialdehyde (MDA), and antioxidant enzymes were measured. One-way ANOVA and Tukey post-hoc tests were used to analyze the data. Results: Serum and hippocampal levels of lactate as well as hippocampal levels of MCT2, SIRT1, FOXO3, LC3, PINK1, Parkin, and antioxidant enzymes were higher while hippocampal levels of Aß, TAU, and MDA were lower in T2D+EX compared to T2D group (P-value<0.05). Conclusion: HIIT could improve mitophagy through Lactate-SIRT1-FOXO3-PINK1/Parkin signaling in the hippocampus of rats with T2D reducing the accumulation of Tau and Aß, which may reduce the risk of memory impairments.

Whole body vibration therapy and diabetes type 2: a systematic review and meta-analysis.

Background: Vibration platforms have demonstrated systemic effects generated by the use of mechanical vibrations, which are similar to those of any physical activity. The effect that whole body vibration (WBV) generates on the organism could be recommended in Diabetes Mellitus 2 (DM 2) patients. Objective: To systematically review and meta-analyze the available evidence on the effects of WBV on glycemic control in patients with DM 2. Material and methods: Exhaustive bibliographic searches were carried out until October 2023 in different biomedical portals and databases: Public Medline (PubMed), Scientific Electronic Library Online (SciELO), VHL Regional Portal, Cochrane Central and Latin American and Caribbean Literature in Health Sciences (LILACS). Randomized clinical trials based on the effects of Whole Body Vibration on glycosylated hemoglobin levels, with control group and participants were non-insulin dependent were the inclusion criteria. Two reviewers extracted data independently. A third reviewer was available for discrepancies. Results: Six articles with 223 participants met the criteria and were included in the systematic review; only four of them met the criteria to be part of the meta-analysis. This meta-analysis reveals a positive and significant effect size (µ ê=0.5731), indicating a substantial difference between the groups studied. Although there is some variability between studies (heterogeneity of 30.05%), the overall direction of the effects is consistent. These findings conclusively suggest the presence of a significant influence of the variable evaluated, underscoring the robustness and consistency of the relationship observed in the literature reviewed. Conclusion: There are no conclusive results due to the lack of data for some variables, which prevents comparison; but WBV may be an effective therapy to improve glycemic control in DM 2 patients. More studies with more patients and longer follow-up are needed.

Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Heart Failure in Patients With Type 2 Diabetes Mellitus: A Systematic Review.

Type 2 diabetes mellitus (T2DM) is a major global health concern with a strong association with increased cardiovascular morbidity and mortality. The prevalence of heart failure is significantly higher in the T2DM population compared to non-diabetic individuals. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have emerged as a promising therapeutic class for managing T2DM, with potential cardioprotective effects. This systematic review aims to comprehensively evaluate the impact of SGLT-2 inhibitors on cardiovascular outcomes in adult patients with T2DM. A comprehensive electronic search was conducted across multiple databases and registries from May 8 to June 6, 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Studies published between January 2019 and June 6, 2024 that evaluated the effects of SGLT-2 inhibitors on cardiovascular outcomes in adults with T2DM were included. The risk of bias was assessed using appropriate tools based on the study design. A narrative synthesis was planned to summarize the findings. The search strategy identified 25 studies (22 randomized controlled trials, three cohort studies) for inclusion in the systematic review. Most of the included studies demonstrated a low overall risk of bias, although some observational studies had some limitations. The studies investigated the effects of various SGLT-2 inhibitors, including empagliflozin, canagliflozin, dapagliflozin, and others, on cardiovascular endpoints such as heart failure-related hospitalizations, mortality, cardiac structure and function, and biomarkers. The findings suggest that SGLT-2 inhibitors may have a beneficial impact on reducing the risk of heart failure-related hospitalizations and potentially improving other cardiovascular outcomes in patients with T2DM. This comprehensive systematic review provides valuable insights into the emerging role of SGLT-2 inhibitors in mitigating cardiovascular complications associated with T2DM. The findings have important clinical implications and may inform evidence-based guidelines and treatment strategies aimed at improving cardiovascular outcomes in this high-risk patient population.

Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss?

Recent studies have shown that pharmacologic weight loss with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination therapies is approaching magnitudes achieved with surgery. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. This primer aims to address whether muscle-related changes associated with weight loss treatments such as GLP-1 RAs may be maladaptive (ie, adversely affecting muscle health or function), adaptive (ie, a physiologic response to weight loss maintaining or minimally affecting muscle health or function), or perhaps an enhanced response to weight loss (ie, improved muscle health or function after treatment). Based on contemporary evidence with the addition of studies using magnetic resonance imaging, skeletal muscle changes with GLP-1 RA treatments appear to be adaptive: changes in muscle volume z-score indicate a change in muscle volume that is commensurate with what is expected given aging, disease status, and weight loss achieved, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function. Nevertheless, factors such as older age and prefrailty may influence the selection of appropriate candidates for these therapies because of risk for sarcopenia. Several pharmacologic treatments to maintain or improve muscle mass designed in combination with GLP-1-based therapies are under development. For future development of GLP-1-based therapies (and other therapies) designed for weight loss, as well as for patient-centered treatment optimization, the introduction of more objective and comprehensive ways of assessing muscle health (including accurate and meaningful assessments of muscle quantity, composition, function, mobility, and strength) is important for the substantial numbers of patients who will likely be taking these medications well into the future.

Importance of the Hemoglobin Glycation Index for Risk of Cardiovascular and Microvascular Complications and Mortality in Individuals with Type 2 Diabetes.

Background: This study investigated the prognostic importance of the hemoglobin glycation index (HGI) for macrovascular and microvascular outcomes, mortality, and hypoglycemia occurrence in a type 2 diabetes cohort and compared it to glycated hemoglobin (HbA1c). Methods: Baseline and mean first-year HGI and HbA1c, and the variability thereof, were assessed in 687 individuals with type 2 diabetes (median follow-up, 10.6 years). Multivariable Cox regression was conducted to evaluate the associations of HGI and HbA1c parameters with macrovascular (total and major cardiovascular events) and microvascular outcomes (microalbuminuria, advanced renal failure, retinopathy, and peripheral neuropathy), mortality (all-cause and cardiovascular), and moderate/severe hypoglycemia occurrence. Results: During follow-up, there were 215 total cardiovascular events (176 major) and 269 all-cause deaths (131 cardiovascular). Microalbuminuria developed in 126 patients, renal failure in 104, retinopathy in 161, and neuropathy in 177. There were 90 hypoglycemia episodes. Both HGI and HbA1c predicted all adverse outcomes, except microalbuminuria and hypoglycemia. Their adjusted risks were roughly equivalent for all outcomes. For example, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), estimated for 1 standard deviation increments, of mean first-year HGI were 1.23 (1.05 to 1.44), 1.20 (1.03 to 1.38), 1.36 (1.11 to 1.67), 1.28 (1.09 to 1.67), and 1.29 (1.09 to 1.54), respectively, for cardiovascular events, all-cause mortality, renal failure, retinopathy, and neuropathy; whereas the respective HRs (95% CIs) of mean HbA1c were 1.31 (1.12 to 1.53), 1.28 (1.11 to 1.48), 1.36 (1.11 to 1.67), 1.33 (1.14 to 1.55), and 1.29 (1.09 to 1.53). Conclusion: HGI was no better than HbA1c as a predictor of adverse outcomes in individuals with type 2 diabetes, and its clinical use cannot be currently advised.

Recent trends in GLP-1 RA and SGLT2i use among people with type 2 diabetes and atherosclerotic cardiovascular disease in the USA.

INTRODUCTION: This study aimed to assess recent trends in the US use of glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD), including incident use following newly diagnosed ASCVD. RESEARCH DESIGN AND METHODS: This real-world, retrospective observational study used de-identified data from the TriNetX Dataworks-USA network. A longitudinal analysis of cross-sectional data (interval: January 01, 2018 to December 31, 2022) assessed the yearly prevalent use of GLP-1 RA and SGLT2i. A nested cohort study (January 01, 2017 to January 31, 2023) assessed the proportions of patients with T2D newly prescribed GLP-1 RAs and SGLT2is after incident ASCVD diagnosis. RESULTS: Prevalent use of GLP-1 RA and/or SGLT2i increased from 9.2% of patients in 2018 to 27.1% in 2022, with eligible annual patient numbers ranging from 279,474 to 348,997. GLP-1 RA-alone use rose from 5.2% to 9.9% and SGLT2i-alone use rose from 2.8% to 12.2% over this interval. Incident use of GLP-1 RA and/or SGLT2i within the year following ASCVD diagnosis increased from 5.9% to 17.0% (2018-2022). For GLP-1 RA alone, this increase was from 3.6% to 7.8%, while for SGLT2i alone, it was from 1.8% to 7.0%. CONCLUSIONS: Use of GLP-1 RAs/SGLT2is in patients with T2D and ASCVD has increased in recent years in the USA, but remains suboptimal given the prevalence of ASCVD and its high morbidity and mortality.

Protective Potential of Cicerbita alpina Leaf Extract on Metabolic Disorders and Oxidative Stress in Model Animals.

Metabolic disorders (MDs) include disease states such as diabetes mellitus, obesity, dyslipidemia, hyperuricemia, etc., affecting about 30% of the planet's population. The purpose of the present study was to investigate the protective potential of Cicerbita alpina leaf extract (ECA) against chemically induced type 2 diabetes in Wistar rats. Additionally, some biochemical parameters in the blood serum and liver, as well as histopathological investigation, were also performed. Quantitative analysis of the major compounds in the used extract was performed using ultrahigh-performance liquid chromatography-diode array detection (UHPLC-DAD) analyses using the external standard method. C. alpina extract revealed a beneficial effect on MDs, lowering blood sugar levels and MDA quantity in the liver, increasing the reduced glutathione level, and increasing antioxidant enzyme activity. Cichoric acid (CA) (91.93 mg/g dry extract (de) ± 4.64 mg/g de) was found to be the dominant compound in the extract, followed by caftaric (11.36 ± 2.10 mg/g de), and chlorogenic acid (CGA) (9.25 ± 0.05 mg/g de). In conclusion, C. alpina leaf extract (ECA) is rich in caffeoyltartaric and caffeoylquinic acids and provides beneficial effects on the diabetic animal model.

Metabolomics Revealed the Effects of Momordica charantia L. Saponins on Diabetic Hyperglycemia and Wound Healing in Mice.

Momordica charantia L. saponins (MCS) may promote wound-healing properties but the underlying mechanisms are unclear. This study aimed to examine the effects and mechanisms of MCS on diabetic wounds. The results have shown that higher MCS intake lowered fasting blood glucose levels, serum lipids, and lipopolysaccharides in diabetic mice. MCS-treated diabetic mice exhibited faster wound healing than the diabetic control groups. After three days, the diabetic control groups exhibited a wound area reduction of only 19.3%, while a 39.75% reduction was observed following high-dose MCS treatment. Five potential biomarkers were screened in the metabolomics study. The results revealed that MCS mainly regulated glycerophospholipid metabolism, fructose and mannose metabolism, steroid hormone biosynthesis, pyrimidine metabolism, and the Krebs cycle, thus affecting wound healing. Overall, MCS could not only exert a hypoglycemic effect but also promote diabetic wound healing, making it a potential treatment option for diabetes-related wounds.

Changes in the incidence of type 2 diabetes in Australia, 2005-2019, overall and by socio-demographic characteristics: a population-based study.

OBJECTIVES: To estimate changes in the incidence of clinically diagnosed type 2 diabetes in Australia, overall and by age, sex, socio-economic disadvantage, geographic remoteness, and country of birth. STUDY DESIGN: Population-based study; analysis of National Diabetes Services Scheme (NDSS) data (age-period-cohort models). SETTING, PARTICIPANTS: Data were extracted for incident cases of type 2 diabetes, 1 January 2005 to 31 December 2019, in residents of the Australian Capital Territory, New South Wales, Queensland, and Victoria aged 20 years or older registered with the NDSS. The numbers of people at risk were obtained from the Australian Bureau of Statistics. MAIN OUTCOME MEASURES: Changes in the incidence of type 2 diabetes, 2005-2019, by age, postcode-level socio-economic disadvantage (Index of Relative Socioeconomic Disadvantage) and remoteness (major city, inner regional, outer regional/remote/very remote), and country of birth, stratified by sex. RESULTS: During 2005-2019, 741 535 people aged 20 years or older with incident type 2 diabetes were registered with the NDSS; 421 190 were men (56.8%). Overall, the incidence of type 2 diabetes increased with age (until about age 70 years) and socio-economic disadvantage for both sexes; it was higher in inner regional areas than in major cities or outer regional/remote/very remote areas during 2005-2015, but highest among people in major cities after 2015. The age-standardised incidence of type 2 diabetes increased during 2005-2010, both among men (annual percentage change [APC], 4.4%; 95% confidence interval [CI], 3.6-5.2%) and women (APC, 2.9%; 95% CI, 2.2-3.7%); it declined during 2010-2019 among both men (APC, -5.2%; 95% CI, -5.4% to -4.9%) and women (APC, -6.5%; 95% CI, -6.8% to -6.2%). In general, similar patterns (but of differing magnitude) applied to all age, sex, socio-economic disadvantage, and remoteness groups. However, the incidence of type 2 diabetes increased during 2011-2019 among people born in Asia, North Africa and the Middle East, and the Pacific Islands. CONCLUSIONS: The incidence of type 2 diabetes in Australian adults declined during 2010-2019 across all age, sex, socio-economic disadvantage, and remoteness groups, but increased among people from Asia, North Africa and the Middle East, and the Pacific Islands.

Evaluation of Lipid Profile Modulation by Berberis asiatica, Withania somnifera, and Their Synergy in Type 2 Diabetic Wistar Rats.

Introduction Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and hyperglycemia, leading to complications such as dyslipidemia, which increases cardiovascular risks. Current treatments for dyslipidemia often have undesirable side effects. This study aims to evaluate the effects of Berberis asiatica (BA), Withania somnifera (WS), and their combination in the ratio of 1:1 on the lipid profile in T2DM-induced Wistar rats. Additionally, the study investigates the potential synergistic effects of these two herbs. Materials and methods Mature albino Wistar rats of both sexes were employed, weighing 150-250 g. Rats were obtained from the Central Animal House of Krishna Institute of Medical Sciences and kept under standard laboratory conditions. The study was conducted per the guidelines set by the Committee for Control and Supervision of Experiments on Animals (CCSEA). T2DM was induced using streptozotocin (STZ) and nicotinamide (NIC). Thirteen groups of rats were formed, including normal control (NC), diabetic control (DC), and various treatment groups received varying dosages of BA, WS, their polyherbal combination (PHC), and the conventional medications metformin (MET) and glimepiride (GLI). Lipid profiles were measured, and the data were analyzed using one-way ANOVA, followed by the Tukey-Kramer post-hoc test. Results The study revealed that both BA and WS showed statistically significant lipid-lowering effects in diabetic rats. The BA-treated groups displayed a statistically significant and considerable decrease in total cholesterol (TC) and low-density lipoprotein (LDL) levels compared to the DC group. Similarly, WS-treated groups also showed statistically significant reduced levels of TC and LDL, along with an increase in high-density lipoprotein (HDL). The PHC of BA and WS exhibited enhanced lipid-lowering effects compared to individual treatments. No significant differences in triglyceride (TG) levels were observed among the treatment groups. Conclusion BA and WS, individually and in combination, effectively modulate lipid profiles in T2DM rats. Their synergistic effects provide a promising alternative for managing dyslipidemia in diabetic patients. Further research is needed to determine the clinical consequences of these findings.

Neuroprotective Effects of Bexarotene and Icariin in a Diabetic Rat Model.

Objective Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder affecting over 400 million people globally, is increasingly recognized for its detrimental impact on the central nervous system. T2DM is linked to neurodegenerative diseases like Alzheimer's and vascular dementia. This study investigates the neuroprotective effects of bexarotene and icariin in a T2DM rat model, focusing on brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and neurofilament-light chain (NfL) levels. Methods Before the study, rats underwent fasting blood glucose tests, lipid profile assessments, and general health evaluations, followed by a high-fat diet for two weeks and a single streptozotocin dose (35 mg/kg). Rats with fasting blood glucose levels ≥250 mg/dl were classified as diabetes mellitus (DM) and continued on the high-fat diet throughout the experiment. Forty-seven male Wistar Albino rats were divided into six groups: a healthy control group, a DM control group, a DM group treated with bexarotene, a DM group treated with icariin, and two DM groups treated with combinations of low and high doses of bexarotene and icariin. After the 45-day treatment, blood samples were collected under thiopental sodium anesthesia, with HbA1c (glycosylated hemoglobin) and hematological parameters analyzed within eight hours, and serum stored at -80°C for further analysis. The animals were then euthanized, and brain tissues were harvested, frozen, and stored at -80°C until further examination. Brain tissues were analyzed for BDNF, GFAP, and NfL levels using ELISA (enzyme-linked immunosorbent assay). For comparing multiple groups, the Kruskal-Wallis test was applied to nonparametric data, and one-way ANOVA was used for parametric data, followed by Bonferroni's post hoc test for pairwise comparisons. Statistical significance was determined with two-tailed tests at p < 0.05. Results Significant changes in GFAP levels were observed across groups (p < 0.001). The DM control group showed the highest GFAP levels, while treatment groups exhibited reductions. The DM control group also showed the highest BDNF levels, while treatment groups exhibited reductions. The DM control group showed the lowest NfL levels, while treatment groups exhibited increments. Conclusion This study highlights the neuroprotective potential of bexarotene and icariin in a diabetic rat model, evidenced by significant changes in GFAP levels. The lack of significant changes in BDNF and NfL suggests that longer study durations may be necessary to observe these effects. Future research should include extended study periods, larger sample sizes, varied dosages, and comprehensive behavioral assessments to better understand the therapeutic potential of these agents.

Serum isthmin-1 is a potential biomarker for metabolic dysfunction associated fatty liver disease in patients with metabolic syndrome and type 2 diabetes mellitus.

INTRODUCTION: Metabolic dysfunction associated fatty liver disease (MAFLD) is a prevalent condition in patients with type 2 diabetes mellitus (T2DM). Isthmin-1 (ISM1) is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis. Although ISM1 has been shown to be associated with T2DM, its role in patients with MAFLD and metabolic syndrome (MetS) remains insufficiently examined. This study aimed to investigate the relationship between serum ISM1 and MAFLD in patients with T2DM and the potential involvement of MetS in this association. RESEARCH DESIGN AND METHODS: A total of 250 participants were divided into four groups: 60 patients with T2DM and MAFLD, 60 with newly diagnosed T2DM, 60 with MAFLD, and 70 healthy controls. Serum ISM1 levels were measured using ELISA. The distribution of ISM1 concentration in the combined data was divided into quartiles, and the Cochran-Armitage trend test was performed to estimate the significant trends across increasing quartiles. RESULTS: Compared with the controls, patients with coexisting MAFLD, MetS, and T2DM exhibited significantly elevated serum ISM1 concentrations. Serum ISM1 levels in the overweight/obese group were also higher than those in the lean group. Serum ISM1 levels were positively correlated with body mass index (BMI), uric acid, alanine aminotransferase, aspartate aminotransferase, total cholesterol (TC), low-density lipoprotein cholesterol, fasting insulin, and homeostasis model assessment of insulin resistance and negatively associated with age and high-density lipoprotein cholesterol (HDL-C). BMI, TC, and HDL-C were independently associated with serum ISM1 concentration. The relative risks for MAFLD, T2DM, and T2DM with MAFLD increased significantly with higher ISM1 quartiles. Furthermore, a positive correlation was observed between serum ISM1 levels and the number of MetS components, with the elevated plasma levels of ISM1 escalating the risk of developing MetS to some extent. CONCLUSIONS: The combination of ISM1 with TG and UA was identified as the best predictive factor for diagnosing MAFLD and MetS, potentially due to their contribution to aggravating the metabolic state.

The Association of Weight Categories in Adolescence with Cardiovascular Morbidity in Young Adult Israeli Arabs-A Nationwide Study.

Objectives. The health consequences of adolescent obesity are understudied in young adult Israeli Arabs. We aimed to evaluate the association of weight categories during adolescence with hypertension (HTN), diabetes mellitus type 2 (DM2), and the composite endpoint of ischemic stroke (IS), myocardial infarction (MI), and heart failure (HF) in young adult Israeli Arabs on a nationwide level. Methods. A retrospective cohort study of 53,726 Arab adolescents born from 1988-1992 was conducted. The cohort was followed, beginning with BMI measurements at ages 17-19 years, until whichever came first among the diagnosis of outcome disease, death, discontinuation of health insurance, or age of 30 years. Results. The incidence (95% CI) of HTN, DM2, and the composite endpoint of IS, MI, and HF was 138.2 (129.1-147.9), 136.7 (127.6-146.3), and 27.3 (23.3-31.7) cases per 105 person-years, respectively. The risk for DM and HTN increased gradually, starting from the 'overweight' category, and reaching fully adjusted HRs (95% CI) of 2.80 (1.82-4.30), and 1.97 (1.31-2.96), respectively, in the 'class 3 obesity' category. The Hazard ratio (HR) for the composite endpoint, its incidence and components, was highest in the 'overweight' category (aHR of 1.64 (1.08-2.50)). Conclusions. The findings emphasize the long-term health consequences of adolescent obesity in early adulthood and, hence, the need for interventions aimed at reducing the rate of adolescent overweight and obesity. The finding of a very high rate of DM2 incidence in early adulthood, even among adolescents without obesity, necessitates an integrated public health approach to all risk factors to prevent DM2 in this population.

Pathogenic Mechanisms That May Link Periodontal Disease and Type 2 Diabetes Mellitus-The Role of Oxidative Stress.

Given the posited role of oxidative stress in the pathogenesis of both periodontitis and type 2 diabetes mellitus (T2DM), it may also serve as a link between these highly prevalent chronic inflammatory diseases. This view is supported by an ample body of evidence indicating that the severity and progression of periodontitis is in part driven by diabetes, while periodontal infection may hinder the attainment of adequate glycemic control in diabetic patients. Thus, this review focuses on the potential synergistic interactions along the oxidative stress-inflammation pathway characterizing both conditions. Because periodontitis and T2DM share the same risk factors and compromise patients' quality of life, to develop effective strategies for combatting both conditions, their mutual influence needs to be explored.

Insulin Resistance in Long COVID-19 Syndrome.

Background: The COVID-19 pandemic has caused severe health issues worldwide and contributed to huge financial losses. Key comorbidities linked to an increased risk of severe COVID-19 and higher mortality rates include cardio-metabolic disorders such as type 1 and type 2 diabetes mellitus (T1DM and T2DM), atherosclerotic cardiovascular disease, chronic kidney disease, hypertension, heart failure, and obesity. The persistence of symptoms even after the acute phase is over is termed long COVID-19 syndrome. This study aimed to evaluate the relationship between long COVID-19 syndrome and the development of insulin resistance in previously non-diabetic patients. Methods: A prospective observational study was performed on 143 non-diabetic patients who had tested positive for SARS-CoV-2 infection by a PCR test and were hospitalized in our hospital between January 2020 and December 2022. The clinical and para-clinical data at 0, 4, and 12 months of hospital admission for post-COVID-19 infection follow-up was collected and labeled as t0, t4, and t12. Blood glucose, insulin, and C-peptide levels were measured at the beginning and further at 2, 5, 10, and 30 min after the intravenous arginine stimulation test. Similarly, BMI was calculated, and hs-CRP and ESR levels were noted. The results obtained were statistically analyzed. Results: More than one-third (30.7%) of the included patients developed long COVID-19 syndrome. It was found that 75% of patients with long COVID-19 hospitalized in our clinic developed diabetes within a year of acute infection with COVID-19; therefore, it can be said that the presence of long COVID-19 is a major risk for an altered metabolic status, which can cause diabetes. When comparing the glycemia levels (106 mg/dL) with the BMI at t0, t4, and t12 time intervals, the p-values were found to be 0.214, 0.042, and 0.058, respectively. Almost 62% of the patients having BMI > 30 kg/m2 were found to have an increase in blood glucose levels at 1 year. Similarly, insulin resistance was noted during this interval. A negative correlation of 0.40 for hsCRP and 0.38 for ESR was noted when compared with acute infection with COVID-19. Conclusions: The association between long COVID-19 and insulin resistance highlights the varied and widespread impacts of SARS-CoV-2 infection. Addressing the complexities of long COVID-19 requires a holistic strategy that encompasses both respiratory and metabolic considerations, which is crucial for enhancing the well-being of those enduring this persistent condition.

Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy.

AIM: To investigate the efficacy of Palmitoylethanolamide (PEA, 300 mg), Superoxide Dismutase (SOD, 70 UI), Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), nicotinamide (9 mg), and minerals (Mg 30 mg, Zn 2.5 mg) in one tablet in people with Diabetic Neuropathy (DN). PATIENTS-METHODS: In the present pilot study, 73 people (age 63.0 ± 9.9 years, 37 women) with type 2 Diabetes Mellitus (DMT2) (duration 17.5 ± 7.3 years) and DN were randomly assigned to receive either the combination of ten elements (2 tablets/24 h) in the active group (n = 36) or the placebo (n = 37) for 6 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured vibration perception threshold (VPT) with biothesiometer, and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Sudomotor function was assessed with SUDOSCAN, which measures electrochemical skin conductance in hands and feet (ESCH and ESCF). Pain score (PS) was assessed with Pain DETECT questionnaire. Quality of life was assessed by questionnaire. RESULTS: In the active group, there was a large improvement of pain (PS from 20.9 to 13.9, p < 0.001). There was also a significant improvement of vitamin B12 (B12) levels, MNSIQ, SNCV, VPT, and ESCF (222.1 vs. 576.3 pg/ mL, p < 0.001; 6.1 vs. 5.9, p = 0.017; 28.8 vs. 30.4, p = 0.001; 32.1 vs. 26.7, p = 0.001; and 72.2 vs. 74.8, p < 0.001 respectively). In the placebo group, neither pain (21.6 vs. 21.7, p = 0.870) or any other aforementioned parameters changed significantly, and MNSIE worsened (2.9 vs. 3.4, p < 0.001). As a result, changes from baseline to follow-up in pain, B12 levels, VPT, and MNSIQ differed significantly between the two groups (p < 0.001, 0.025, 0.009, and <0.001, respectively). CARTs, SNAP, ESCH did not significantly change in either of the two groups. CONCLUSIONS: The combination of the ten elements in one tablet for 6 months at a daily dose of two tablets in people with DN significantly improves pain, vibration perception threshold, and B12 levels.

Advances in insulin: a review of icodec as a novel once-weekly treatment for type 2 diabetes.

Type 2 diabetes (T2D) is a chronic condition that requires not only a team-based approach but also substantial self-management by those affected. Patient-clinician barriers such as lack of educational resources, hesitancy in initiation of therapy, concerns over treatment-related side effects, frequency of dosing, and the establishment of treatment goals, can prevent a patient from achieving optimal glycemic management. Recently, advances in diabetes technology and insulin formulations have helped to address some of these concerns. Insulin icodec, the first once-weekly basal insulin analog, has demonstrated efficacy and safety comparable to traditional basal insulin formulations. Since clinicians and patients may benefit from a once-weekly therapy, this review sought to evaluate the potential clinical implications of insulin icodec. A literature search was performed using PubMed, Google Scholar, and ClinicalTrials.gov up to 31 January 2024. Key search terms such as once-weekly basal insulin, icodec, and ONWARDS were utilized to compile relevant publications. Further, studies involving patients living with T2D on once-weekly insulin icodec compared with once-daily basal insulin were considered for this review. Findings from this review suggest insulin icodec can offer a reduced dosing frequency that may improve medication adherence, provide effective glycemic management, and a comparable safety profile to existing basal insulins. In summary, insulin icodec may help to remove patient-clinician barriers associated with suboptimal glycemic management with its once-weekly dosing schedule. Clinicians can further support a patient's ability to self-manage the disease through continued monitoring and guidance on the use of icodec.

Type 2 diabetes can be a challenging illness to manage since patients and clinicians often encounter obstacles such as limited access to educational resources, concerns about starting treatment, worries about side effects, and inconvenient dosing schedules. While recent advancements in diabetes technology and insulin formulations have helped, there's still a need for more information to ease concerns about treatment. Insulin icodec, an insulin taken just once a week, has shown to be just as effective and safe as traditional daily insulins. Since both clinicians and patients may benefit from the use of a once-weekly therapy, we evaluated the possible impact of insulin icodec on clinical practice and patient outcomes. To do this, researchers collected and read scientific articles published online on or before 31 January 2024. Key search terms were used during the online search. After a review of the articles, the authors found that insulin icodec could not only simplify treatment by reducing the number of injections needed but also control blood sugar as effectively as existing insulin options. In summary, insulin icodec has the potential to address many of the challenges associated with managing type 2 diabetes, offering a simpler dosing schedule that could improve adherence and overall blood sugar. Continued support and guidance from clinicians and interdisciplinary team members can further enhance a patient's ability to manage their diabetes effectively with insulin icodec.

Benefit and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors in Older Patients with Type 2 Diabetes Mellitus.

People with type 2 diabetes mellitus (T2DM) are at higher risk of developing cardiovascular disease, heart failure, chronic kidney disease, and premature death than people without diabetes. Therefore, treatment of diabetes aims to reduce these complications. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown beneficial effects on cardiorenal and metabolic health beyond glucose control, making them a promising class of drugs for achieving the ultimate goals of diabetes treatment. However, despite their proven benefits, the use of SGLT2 inhibitors in eligible patients with T2DM remains suboptimal due to reports of adverse events. The use of SGLT2 inhibitors is particularly limited in older patients with T2DM because of the lack of treatment experience and insufficient long-term safety data. This article comprehensively reviews the risk-benefit profile of SGLT2 inhibitors in older patients with T2DM, drawing on data from prospective randomized controlled trials of cardiorenal outcomes, original studies, subgroup analyses across different age groups, and observational cohort studies.