The association of isocarbophos and isofenphos with different types of glucose metabolism: The role of inflammatory cells.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Visceral Fat and Diabetes: Associations With Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is increasing globally. Noninvasive methods, such as bioelectrical impedance analysis (BIA), which measures body composition, including visceral fat, are gaining interest in evaluating MASLD patients. Our study aimed to identify factors associated with significant liver fibrosis, compare noninvasive scores, and highlight the importance of visceral fat measurement using BIA. Methods: MASLD patients seen in our out-patient department underwent comprehensive evaluations, including liver stiffness using transient elastography, body composition analysis using BIA, and metabolic measurements. Significant fibrosis was defined as a liver stiffness measurement of ≥8.2 kPa. Using multivariate analysis, we identified factors associated with significant liver fibrosis and compared four noninvasive scores with a novel diabetes-visceral fat 15 (DVF15) score. Results: We analyzed data from 609 MASLD patients seen between February 2022 and March 2023. The median age was 43 years (81% male). Among these, 78 (13%) had significant fibrosis. Patients with significant fibrosis had higher rates of type 2 diabetes (41% vs 21%, P < 0.001) and elevated levels of aspartate aminotransferase, alanine aminotransferase, hemoglobin A1c, Fibosis-4, aspartate-aminotransferase-to platelet-ratio index, and NAFLD fibrosis scores. They also exhibited higher visceral and subcutaneous fat. Binary logistic regression revealed type 2 diabetes and a visceral fat level of >15% as associated with significant liver fibrosis. Additionally, the DVF15 score, combining these factors, showed a modest area under the receiver operating characteristic curve of 0.664 (P < 0.001). Conclusion: Our study identified diabetes and high visceral fat as factors associated with significant liver fibrosis in MASLD patients. We recommend that visceral fat measurement using BIA be an essential part of MASLD evaluation. The presence of either diabetes or a visceral fat level of >15% should prompt clinicians to check for significant fibrosis in MASLD patients. Further research is warranted to validate our findings and evaluate the utility of the DVF15 score in larger cohorts and diverse populations.

Evaluating the Causal Effect of Type 2 Diabetes on Alzheimer's Disease Using Large-Scale Genetic Data.

BACKGROUND: Alzheimer's disease (AD) has a high comorbidity with type 2 diabetes (T2D). However, there is still some controversy over whether T2D has a causal impact on AD at present. OBJECTIVES: We aimed to reveal whether T2D has a causal effect on AD using large-scale genetic data. METHODS: Firstly, we performed a primary two-sample Mendelian randomization (MR) analysis to assess the potential causal effects of T2D on AD. For this analysis, we used the largest available genome-wide association studies (GWAS) T2D (T2D1, including 80,154 cases and 853,816 controls) and AD (AD1, including 111,326 cases and 677,663 controls) datasets. Additionally, we performed a validation MR analysis using two largely overlapping-sample datasets from FinnGen, including T2D (T2D2, including 57,698 cases and 308,252 controls) and AD (AD2, including 13,393 cases and 363,884 controls). In all MR analyses, the inverse variance-weighted method was used as the primary analysis method, supplemented by the weighted-median and MR-Egger techniques. RESULTS: In the primary analysis, we found that T2D was not associated with the risk of AD (OR: 0.98, CI: 0.95-1.01, P=0.241). Similarly, no significant association was detected in the validation MR analysis (OR: 0.97, CI: 0.64-1.47, P=0.884). CONCLUSION: Our findings provide robust evidence that T2D does not have a causal impact on AD. Future studies need to further explore the effect of T2D on the non-AD components of the dementia phenotype.

Serum levels of the incretin-like peptide 26RFa are diminished in women living with obesity and diabetes and restored after sleeve gastrectomy: Results from the prospective pilot RFa-Ba-S study.

AIM: To investigate the evolution of the incretin-like peptide 26RFa in a prospective cohort of women living with obesity with or without type 2 diabetes (T2D) before and after sleeve gastrectomy (SG). METHODS: In this study, a total of 61 women were divided into three groups: women living with severe obesity without T2D (WlwOB group), women living with severe obesity and T2D (WlwOB-T2D group) and lean healthy volunteers (control group). Serum 26RFa concentrations were measured using a 26RFa enzyme-linked immunosorbent assay developed specifically for this study during meal tests before SG, and 30 and 180 days after SG. RESULTS: At baseline, serum 26RFa levels were reduced in the WlwOB (P < .05) and WlwOB-T2D (P < .01) groups compared with controls. In the WlwOB-T2D group, fasting 26RFa levels were found to increase throughout the entire follow-up period up to 6 months after the SG (P < .001). During the meal tests, serum 26RFa levels increased, especially in the WlwOB-T2D group at baseline. At the end of the follow-up, the profile of 26RFa concentrations obtained during the meal test in patients with severe obesity and T2D was similar to that of the controls. CONCLUSIONS: This prospective clinical study provides the first evidence that circulating 26RFa is altered mainly in WlwOB-T2D, and that these defects are partially reversed after SG.

Assessments of coagulation profile among good glycemic control and poor glycemic control type 2 diabetic patient attending at Wolkite University specialized hospital, Central Ethiopia: a comparative study.

INTRODUCTION: Diabetes Mellitus (DM) is a worldwide health issue that is defined by elevated blood glucose levels and impaired metabolism of fat, carbohydrates, and proteins. Atherosthrombotic events are very likely to occur in patients with diabetes mellitus. This results in the development of both microvascular and macrovascular complications. OBJECTIVE: To compare the coagulation profile parameters between patients with good glycemic control and poor glycemic control and to evaluate the association of coagulation profile and glycemic control in type 2 DM patients. MATERIALS AND METHODS: This study was conducted in Wolkite university specialized hospital on 90 type 2 Diabetics patients among which 45 were with good glycemic control and 45 were with poor glycemic control. Seven ml blood samples were collected from each study participant and analyzed to assess coagulation profile including Platelet Count, activated Partial Thromboplastin Time (aPTT), and Prothrombin Time (PT). Using SPSS 21.0, an independent sample t-test was used for statistical analysis. RESULTS: According to the current study, when comparing Type 2 Diabetes with poor glycemic control to those with good glycemic control, there was an increase in PT and aPTT concentration (statistically significant, p < 0.05). The platelet counts of the two groups did not differ significantly. CONCLUSION: People with Type 2 diabetes have altered coagulation profiles, which have demonstrated that hyperglycemia causes abnormalities in coagulation. Patients with Type 2 diabetes who have poor glycemic control are particularly vulnerable to atherothrombotic and hemorrhagic events. In order to prevent the onset of microvascular and macrovascular illness as soon as possible, physicians may find it helpful to evaluate the coagulation profile of diabetic patients.

Bone marrow mesenchymal stem cell and mononuclear cell combination therapy in patients with type 2 diabetes mellitus: a randomized controlled study with 8-year follow-up.

BACKGROUND: To investigate the long-term effects of combining bone marrow mesenchymal stem cells (MSCs) with mononuclear cells (MCs) in the treatment of type 2 diabetes mellitus (T2DM). METHODS: T2DM patients were divided into the combination group (Dual MSC + MC, n = 33), the mononuclear cell group (MC-Only, n = 32) and the control group (Control, n = 31). All groups were treated with insulin and metformin. The Dual MSC + MC group additionally received MSC and MC infusion and the MC-Only group additionally received MC infusion. The patients were followed up for 8 years. The primary endpoint was the C-peptide area under the curve (C-p AUC) at 1 year. This study was registered with clinicaltrial.gov (NCT01719640). RESULTS: A total of 97 patients were included and 89 completed the follow-up. The area under the curve of C-peptide of the Dual MSC + MC group and the MC-Only group was significantly increased (50.6% and 32.8%, respectively) at 1 year. After eight years of follow-up, the incidence of macrovascular complications was 13.8% (p = 0.009) in the Dual MSC + MC group and 21.4% (p = 0.061) in the MC-Only group, while it was 44.8% in the Control group. The incidence of diabetic peripheral neuropathy (DPN) was 10.3% (p = 0.0015) in the Dual MSC + MC group, 17.9% (p = 0.015) in the MC-Only group, and 48.3% in the Control group. CONCLUSIONS: The combination of MSC and MC therapy can reduce the incidence of chronic diabetes complications and improves metabolic control with mild side effects in T2DM patients.

Circulating Interleukin-17A is associated with executive function in middle aged adults with and without type 2 diabetes.

Midlife cardiovascular risk factors such as Type 2 Diabetes (T2DM) and obesity are associated with the later development of cognitive impairment and dementia. Systemic inflammation is postulated as a crucial mechanism, yet there are few studies examining this at the earliest stages prior to overt cognitive impairment. To assess this, we recruited a cohort of middle-aged cognitively-unimpaired individuals with and without uncomplicated T2DM. Comprehensive neuropsychological assessment was performed at baseline and at 4-year follow-up. Ten serum chemokines and cytokines (Eotaxin, MCP-1, MIP-1ß, CXCL10, IL-6, IL-10, IL12p70, IL-17A, IFN-γ and TNF-α) were measured at both baseline and follow-up using high-sensitivity assays. Overall, 136 participants were recruited including 90 with uncomplicated midlife T2DM (age 52.6 ± 8.3; 47% female) and 46 without (age 52.9 ± 8.03; 61% female). Cognitive trajectories were stable over time and did not differ with T2DM. Yet on cross-sectional analyses at both baseline and follow-up, greater circulating IL-17A was consistently associated with poorer performance on tests of executive function/attention (ß: 0.21; -0.40, -0.02, p = 0.03 at baseline; ß: 0.26; -0.46, -0.05, p = 0.02 at follow-up). Associations persisted on covariate adjustment and did not differ by T2DM status. In summary, we provide evidence that greater circulating IL-17A levels were associated with poorer executive function in midlife, independent of T2DM. Long-term follow-up of this and other cohorts will further elucidate the earliest stages in the relationship between systemic inflammation and cognitive decline to provide further mechanistic insights and potentially identify those at greatest risk for later cognitive decline.

Reference gene panel for urinary exosome-based molecular diagnostics in patients with kidney disease.

BACKGROUND: Kidney disease is a severe complication of diabetes that often leads to end-stage renal disease. Early diagnosis is crucial for prevention or delay. However, the current diagnostic methods, with their limitations in detecting the disease in its early stages, underscore the urgency and importance of finding new solutions. miRNAs encapsulated inside urinary exosomes (UEs) have potential as early biomarkers for kidney diseases. The need for reference miRNAs for accurate interpretation currently limits their translational potential. AIM: To identify consistently expressing reference miRNAs from UEs of controls and patients with type 2 diabetesmellitus (T2DM) and biopsy-confirmed kidney diseases. METHODS: miRNA profiling was performed on UEs from 31 human urine samples using a rigorous and unbiased method. The UEs were isolated from urine samples collected from healthy individuals (n = 6), patients with T2DM (n = 13), and T2DM patients who also had kidney diseases (including diabetic nephropathy, n = 5; membranous nephropathy, n = 5; and IgA nephropathy, n = 2) through differential ultracentrifugation. After characterizing the UEs, miRNA expression profiling using microarray technology was conducted. RESULTS: Microarray data analysis identified 14 miRNAs that were consistently expressed in UEs from 31 human samples, representing various kidney conditions: diabetic controls, diabetic nephropathy, membrane nephropathy, IgA nephropathy, and healthy controls. Through in silico analysis, we determined that 10 of these miRNAs had significant potential to serve as reference genes in UEs. CONCLUSION: We identified uniformly expressing UE miRNAs that could serve as reference genes kidney disease biomarkers.

Effect of probiotics on glycemic control and lipid profiles in patients with type 2 diabetes mellitus: a randomized, double blind, controlled trial.

Introduction: This double-blind, placebo-controlled, randomized (1:1) clinical trial was conducted at the West China Hospital, Sichuan University, from March to September 2017. Methods: Eligible participants included adults aged 18 years and older, living in the community, diagnosed with type 2 Diabetes Mellitus according to ADA guidelines, capable of self-managing their diabetes, and able to visit the study site for follow-up. The intervention group received 25 ml of a probiotic beverage containing with over 10^8 CFU/mL of Lactobacillus, administered four times daily. An equal volume of inactivated Lactobacillus was administered to the control group and the control group was administered the same volume of inactivated Lactobacillus. This study aimed to evaluate the effectiveness of probiotics on glycemic control and other diabetes-related outcomes in patients with type 2 diabetes patients. The primary outcomes were changes in HbA1c and FBG levels post-intervention. Investigators, participants, and study site personnel were blinded to the treatment allocation until the conclusion of the study. This double-blind, randomized, placebo-controlled clinical trial was registered in the Chinese Clinical Trial Registry (ChiCTR-POR-17010850). Results: Of the 490 participants screened, 213 were randomized to either the probiotics group (n = 103) or the placebo group (n = 110). After 16 weeks of follow-up, the probiotic group showed reductions in HbA1c [-0.44 (-0.66 to -0.22)] and FBG [-0.97 (-1.49 to 0.46)] post-intervention, similar to the placebo group with reductions in HbA1c [-0.33 (-0.52 to -0.15)] and FBG [-0.90 (-1.32 to -0.47)], but these changes were not statistically significant in PP and ITT analyses (P>0.05). Adverse events were similarly distributed among groups, indicating comparable safety profiles. Discussion: Overall, 16-week probiotic supplementation showed no beneficial effects on glycemic control, lipid profiles, or weight. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=18421, identifier ChiCTR-POR-17010850.

Assessment of correlation between lipid ratios and body mass index in patients with type 2 diabetes mellitus in Sarajevo, Bosnia and Herzegovina.

Objective. Studies that have evaluated correlation between body mass index (BMI) and novel lipid indices such as triglycerides (TG)/high-density lipoprotein-cholesterol (HDL-C), total cholesterol (TC)/HDL-C, and low-density lipoprotein cholesterol (LDL-C)/HDL-C in type 2 diabetes mellitus (T2DM) are scarce. Hence, the aim of the present study was to explore the correlation between BMI and novel lipid indices in Bosnian patients with T2DM. Methods. Present study included 117 patients with T2DM (mean age: 66.51 years) and 68 controls (mean age: 68.37 years). BMI was calculated as weight/height². Lipids were measured by standard methods. TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratios were separately calculated. The differences between the groups were assessed by Student's t-test or Man Whitney U test. Correlations were determined by Spearman's test. Results. In a total sample of T2DM patients, 41.0% were overweight and 44.4% were obese. In the control group, 51.5% of subjects were overweight and 25.0% were obese. In T2DM group, a significant correlation was observed between BMI and HDL-C, LDL-C, TG/HDL, TC/HDL-C, and LDL-C/HDL-C ratios. In the control group, there was a significant correlation found between BMI and HDL-C, TG, TG/HDL, TC/HDL-C, and LDL-C/HDL-C-ratios. Correlation between BMI and other lipid parameters in T2DM and the control group was not determined. Conclusion. The present study showed significant correlation between BMI and novel lipid indices in both T2DM patients and the control group of subjects. Possible explanation for the observed results might be prevalence of overweight and obese participants in this study sample. Since novel lipid indices are used in the prediction of cardiometabolic risk, results obtained in the present study have valuable clinical implications.

Dairy consumption and risk of prediabetes and type 2 diabetes in the Fenland study.

BACKGROUND & AIMS: Limited observational evidence suggests that a higher intake of high-fat dairy may be associated with lower prediabetes risk, while opposite associations have been observed for low-fat milk intake. This study aimed to examine associations between baseline and changes in dairy consumption, risk of prediabetes, and glycaemic status. METHODS: 7521 participants from the prospective UK Fenland study were included (mean age 48.7 ± 2.0 years, 51.9 % female). Dairy intake was measured using self-reported food frequency questionnaires. Associations with prediabetes risk and glycaemic status were analysed using Poisson regression models adjusted for social demographics, health behaviours, family history of diabetes and food group intake. RESULTS: At a mean follow-up of 6.7 ± 2.0 years, 290 participants developed prediabetes (4.3 %). Most dairy products were not significantly associated with prediabetes risk. A higher baseline intake of high-fat dairy (RRservings/day 1.20, 95%CI 1.03-1.39) and high-fat milk (RRservings/day 1.22, 1.01-1.47) were associated with higher prediabetes risk. Conversely, low-fat milk was associated with lower prediabetes risk (RRservings/day 0.86, 0.75-0.98). In the analyses evaluating dietary changes over time, increases in high-fat milk were inversely associated with risk of progressing from normoglycaemia to prediabetes or type 2 diabetes (RRservings/day 0.86, 95%CI 0.75-0.99). CONCLUSIONS: This population-based study showed that most dairy products are not associated with prediabetes risk or progression in glycaemic status. Positive associations of high-fat dairy, high-fat milk, and the inverse association of low-fat milk with prediabetes risk found were inconsistent with prior literature and suggestive of the need for future research on environmental, behavioural, and biological factors that explain the available evidence.

The serum uric acid to serum creatinine ratio is an independent risk factor for type 2 diabetes in community-dwelling elderly: A longitudinal analysis.

BACKGROUND AND AIM: Elevated serum uric acid (SUA) levels are an important marker of metabolic disorders. However, SUA levels largely depend on renal clearance function. This study aims to investigate the relationship between renal function-normalized SUA [SUA to serum creatinine (SCr) ratio] and the risk of developing type 2 diabetes in a community-dwelling elderly population. METHODS AND RESULTS: A retrospective cohort study was conducted on elderly, non-diabetic individuals from the Kunshan community in China, who participated in annual health check-ups between January 2018 and December 2023. The relationship between the baseline SUA/SCr ratio and the risk of type 2 diabetes was examined using Cox regression models, restricted cubic splines (RCS), and subgroup analyses. After a median follow-up of 3.88 years, 778 cases of type 2 diabetes were identified among 7671 elderly non-diabetic individuals. Adjusting for confounding variables, the baseline SUA/SCr ratio was significantly linked to type 2 diabetes risk (P < 0.001). Individuals in the highest SUA/SCr ratio quartile had a 1.323 times higher risk of developing type 2 diabetes compared to those in the lowest quartile (HR = 1.323, 95% CI 1.053-1.661, P = 0.016). RCS analysis further confirmed this positive association. Additionally, subgroup analyses suggested that this relationship was particularly pronounced in female individuals. CONCLUSIONS: In Chinese elderly community residents, the baseline SUA/SCr ratio is linked to the risk of type 2 diabetes. Monitoring this ratio could aid in predicting and assessing the risk of type 2 diabetes.

Efficacy and Safety of Ertugliflozin Compared to Placebo in Patients With Type 2 Diabetes: An Updated Systematic Review and Meta-Analysis.

Background: No comprehensive meta-analysis has evaluated the efficacy and safety of ertugliflozin compared to a placebo in patients with Type 2 diabetes (T2D) until now. This meta-analysis fills this gap in knowledge. Methods: A systematic search was carried out in electronic databases to identify randomized controlled trials (RCTs) that included patients with T2D receiving ertugliflozin in the treatment group and placebo in the control group. The change in HbA1c from the baseline values was the primary outcome, whereas changes in plasma glucose and other metabolic parameters and adverse events (AEs), including hypoglycemia, were the secondary outcomes. Results: Seven RCTs involving 7283 subjects met the inclusion criteria. Ertugliflozin outperformed placebo in reducing HbA1c in both 5 mg (MD -0.62%, 95% CI [-0.80, -0.44], p < 0.00001, I 2 = 91%) and 15 mg (MD -0.69%, 95% CI [-0.91, -0.47], p < 0.00001, I 2 = 93%) doses. A higher proportion of patients achieved HbA1c < 7.0% with ertugliflozin than with placebo. Ertugliflozin was also superior to placebo in lowering fasting plasma glucose (FPG), body weight, and systolic and diastolic blood pressure (BP). Ertugliflozin and placebo had comparable AE profiles, including urinary tract infection (UTI) and hypoglycemia, except for the greater risk of genital mycotic infections (GMIs) with ertugliflozin. Ertugliflozin 5 and 15 mg have equivalent efficacy and safety profiles except for greater weight reduction with ertugliflozin 15 mg. Conclusion: Ertugliflozin has a good glycemic efficacy and a reassuring safety profile in managing T2D. Trial Registration: Registration number: CRD42023456450.

Relationship between advanced glycation end-products and advanced oxidation protein products in patients with type 2 diabetes with and without albuminuria: A cross-sectional survey.

Background and Aims: Literature suggests that oxidative stress plays a crucial role in the progression of diabetes. Since poor glycemic control enhances the formation of advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP) in individuals with diabetes, exploring the association between glycation and oxidative states in diabetes could also shed light on potential consequences. This study evaluated the effects of albuminuria on AGEs and AOPP levels and measured their relationship in participants with type 2 diabetes (T2D) with or without albuminuria. Methods: A cross-sectional, matched case-control study was designed, including 38 T2D subjects with albuminuria and 38 matched T2D subjects with normoalbuminuria. Patients were matched by their body mass index (BMI), age, and duration of diabetes. The unadjusted and adjusted correlation between AGEs and AOPP in the studied groups were analyzed by multiple logistic regression. Using ggplot2, the ties between these two biochemical factors in cases and controls were plotted. Results: This study elucidated a significant association between AGEs and AOPP in participants with normoalbuminuria (r = 0.331, p-value < 0.05), which continued to be significant after controlling for BMI, age, systolic blood pressure (SBP), and diastolic blood pressure (DBP) (r = 0.355, p-value < 0.05). However, there was no significant association between AGEs and AOPP in those with albuminuria in the unadjusted model (r = 0.034, p-value = 0.841) or after controlling for BMI, age, SBP, and DBP (r = 0.076, p-value = 0.685). Conclusion: Oxidation and glycation molecular biomarkers were correlated in patients without albuminuria; however, this association was not observed in those with albuminuria.

Recent advances in precision nutrition and cardiometabolic diseases.

A growing body of research on nutrition omics has led to recent advances in cardiovascular disease epidemiology and prevention. Within the PREDIMED trial, significant associations between diet-related metabolites and cardiovascular disease were identified, which were subsequently replicated in independent cohorts. Some notable metabolites identified include plasma levels of ceramides, acyl-carnitines, branched-chain amino acids, tryptophan, urea cycle pathways, and the lipidome. These metabolites and their associated pathways have been associated with incidence of both cardiovascular disease and type 2 diabetes. Future directions in precision nutrition research include: a) developing more robust multimetabolomic scores to predict long-term risk of cardiovascular disease and mortality; b) incorporating more diverse populations and a broader range of dietary patterns; and c) conducting more translational research to bridge the gap between precision nutrition studies and clinical applications.

Longitudinal Patterns of Ankle-Brachial Index and Their Association With Progression of CKD in Patients With Type 2 Diabetes and Elevated Body Mass Index.

RATIONALE & OBJECTIVE: Ankle-brachial index (ABI) is used to screen for vascular complications in the setting of diabetes. This study sought to examine the relationship of longitudinal ABI data and chronic kidney disease (CKD) progression in patients with type 2 diabetes (T2D) and elevated body mass index (BMI). STUDY DESIGN: A post-hoc analysis of the Look AHEAD trial. SETTING & PARTICIPANTS: This study included 3,631 participants in the Look AHEAD trial with a baseline glomerular filtration rate (eGFR) >60 ml/min/1.73 m2. EXPOSURES: Average ABI and average annual change in ABI were calculated based on annual ABI measurements during the first 4 years of the study. OUTCOME: CKD progression, defined as kidney failure requiring maintenance dialysis or the occurrence of eGFR<60 ml/min/1.73 m2 with a drop of ≥30% at a follow-up visit relative to the first eGFR measurement. ANALYTICAL APPROACH: Restricted cubic spline and Cox proportional hazards models were fit to estimate associations and to explore non-linearity. RESULTS: Over a median follow-up of 10.1 years, 1,051 participants developed CKD progression. There was a reversed J-shaped relationship of CKD progression with average ABI (when ABI <1.17: HR (per SD decrement), 1.23; 95%CI, 1.06-1.42; when ABI ≥ 1.17: HR (per SD increment), 1.10; 95%CI, 1.00-1.22) and average annual change in ABI (when change in ABI <-0.007: HR (per SD decrement), 1.37; 95%CI, 1.12-1.66; when change in ABI ≥-0.007: HR (per SD increment), 1.13; 95%CI, 1.03-1.24). LIMITATIONS: Observational study, potential unmeasured confounding. CONCLUSIONS: Low and high average ABI, even at clinically normal values, as well as decreasing and increasing average annual ABI, were associated a higher risk of CKD progression in patients with T2D and elevated BMI. Monitoring ABI and its changes over time may facilitate CKD risk stratification in patients with T2D.

Bridging brain insulin resistance to Alzheimer's pathogenesis.

Emerging evidence links type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD), with brain insulin resistance (BIR) as a key factor. In a recent study, Lanzillotta et al. reveal that reduced biliverdin reductase-A (BVR-A) impairs glycogen synthase kinase 3ß (GSK3ß) phosphorylation, causing mitochondrial dysfunction and exacerbating brain insulin resistance in the progression of both T2DM and AD.

Irregular breakfast eating in type 2 diabetes mellitus is associated with greater social jetlag and poorer metabolic health.

Circadian disruption, arising from conflict between internal circadian time and behavioural sleep-wake and fasting-feeding rhythms, may contribute to the prevalence of type 2 diabetes mellitus and disease severity. Previous studies have demonstrated a link between irregular breakfast eating and poorer metabolic health. We aimed to further explore the relationships between breakfast habits, circadian misalignment (social jetlag), and metabolic parameters in a cohort of adult participants with type 2 diabetes mellitus. A total of 330 adult participants with type 2 diabetes mellitus attending for routine clinical review completed structured questionnaires to assess habitual sleep timing, chronotype, and social jetlag. Statistical analysis was via inferential groupwise approaches and path analysis to establish interdependencies of effects of social jetlag, chronotype, and breakfast eating regularity on HbA1c. 22.7% of the participants reported eating breakfast five times or fewer a week, and were categorised as irregular breakfast eaters. Compared with those who ate breakfast six or seven times a week, irregular breakfast eaters had significantly higher HbA1c and diastolic blood pressure, were younger and had greater social jetlag. In the path analysis, irregular breakfast eating exerted a direct effect on HbA1c, whilst social jetlag exerted only an indirect effect on HbA1c through breakfast eating regularity. Chronotype did not exert any effect on HbA1c, but did exert an indirect effect on breakfast eating regularity via social jetlag. Our results showed that adult participants with type 2 diabetes mellitus, who ate breakfast irregularly had poorer metabolic health and greater social jetlag. The relationship between social jetlag and glycaemic control appears to be mediated through breakfast eating habits.

Frailty, Body Composition, and Glycemic Control in Older Adults with Type 2 Diabetes.

The relationship between frailty and glycemic control in older adults with diabetes remains uncertain, mainly due to the fact that previous studies have not accounted for measures of body composition. In older adults with diabetes, we examined the association between three types of frailty measures and glycemic control, while accounting for fat-free mass (FFM) and waist circumference (WC). Eighty older adults (age ≥65, 27 women and 53 men, mean age 80.5 ± 0.6 years) had gait speed, Cardiovascular Health Study Index (CHSI), Rockwood Clinical Frailty Scale (RCFS), and glycosylated hemoglobin (HgA1C) measured. HgA1C showed a negative association only with CHSI (standardized ß = -0.255 ± 0.120, p = 0.038), but no association with gait speed or the RCFS. Even after accounting for FFM and WC, we demonstrated a negative association between glycated hemoglobin and increasing frailty in older adults with diabetes.

The risk of type 2-diabetes among persons with intellectual disability: a Danish population-based matched cohort study.

BACKGROUND: Previous research shows that obesity, unhealthy eating, physical inactivity and a high use of psychotropic medications are prevalent among persons with intellectual disability (ID), which might increase the risk of type 2-diabetes (T2DM). This study aims to investigate: (1) whether persons with ID have an increased risk of T2DM compared with an age- and sex-matched reference group and (2) differences in T2DM risk by sex, birth year, ID inclusion diagnosis and ID severity. METHODS: This study is a nationwide cohort study, including 65 293 persons with ID and 659 723 persons in an age- and sex-matched reference group without ID. Incidence rates for T2DM were calculated and Cox proportional regression models were used to estimate adjusted hazard ratios (aHRs) for the association between ID and T2DM. Follow-up began from the 1 January 1977 (when T2DM data were available), participants' 22nd birthday or from the date the participants immigrated to Denmark, whichever came last and continued until the onset of T2DM, emigration, death or end of follow-up (31 December 2021), whichever came first. RESULTS: Persons with ID had more than double risk of T2DM compared with the reference group [aHR = 2.15, 95% confidence interval (CI): 2.09-2.20]. The strongest associations were found among women, persons born between 1980 and 1999 and among persons with mild ID. CONCLUSIONS: Persons with ID have an increased risk of T2DM. This knowledge is important in relation to the development and prioritising of preventive initiatives among persons with ID in the healthcare sector. Future research should focus on the underlying mechanisms that can explain the possible association between ID and T2DM as it allows a more targeted prevention strategy.