Type 2 Diabetes Patients Research Articles

Long-term exposure to NO2 and PM2.5 and the occurrence of chronic kidney disease among patients with type 2 diabetes in Taiwan

BackgroundIndividuals diagnosed with type 2 diabetes (T2D) frequently exhibit chronic kidney disease (CKD) which may be caused by environmental hazards such as exposure to air pollutants. However, limited research has explored the effects of prolonged exposure to air pollutants on CKD development in this population. This study examines the relationship between long-term exposure to air pollutants and CKD incidence in a longitudinal cohort of individuals with type 2 diabetes in Taiwan MethodsBetween 2003 and 2005, we recruited 1316 T2D patients (693 females [52.66 %]; mean age 56.16 ± 8.97 years). Patients were followed until December 31, 2012, with at least two clinical visits. Baseline demographics, medical history, and biomarker levels were collected. The development of CKD was determined by eGFR level < 60 mL/min/1.73 m2. Monthly averages of nitrogen dioxide (NO2) and fine particulate matter [PM ≤ 2.5 μm in aerodynamic diameter (PM2.5)] were acquired from 72 ambient air monitoring stations. The kriging method was employed to estimate the exposure levels to PM2.5, NO2, temperature, and relative humidity in the participants' residential areas. Cox regression with time-dependent covariates regression was applied to assess the impact of long-term exposure to air pollutants and CKD risk. ResultsOf 992 patients with normal renal function at baseline, 411 (41.43 %) experienced CKD occurrence over a median follow-up period of 5.45 years. The incidence of CKD was 93.96 cases per 1000 person-years. In multivariable adjusted models, patients exposed to PM2.5 levels above the third quartile of (>33.44 μg/m3) and NO2 levels above the fourth quartile (>22.55 ppb) were found to have an increased risk of CKD occurrence compared to lower exposure levels. ConclusionsThis longitudinal study highlights the increased risk of CKD in individuals with type 2 diabetes due to prolonged exposure to NO2 and PM2.5, emphasizing the need for tailored air quality management strategies for this high-risk population.

Patients with type 1 diabetes are at elevated risk of developing new hypertension, chronic kidney disease and diabetic ketoacidosis after COVID-19: Up to 40 months' follow-up.

The aim was to investigate whether COVID-19 increases new incidence of hypertension (HTN), chronic kidney disease (CKD) and diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) up to 40 months post-infection. Three groups of patients from the Montefiore Health System in the Bronx (1 March 2020 to 1 July 2023) were studied: T1D patients hospitalized for COVID-19 (H-COVID-19, n = 511), T1D patients with COVID-19 but not hospitalized for COVID-19 (NH-COVID-19, n = 306) and T1D patients without a positive COVID-19 test on record (non-COVID-19, n = 1547). COVID-19 patients were those with a positive polymerase-chain-reaction test on record, and non-COVID-19 patients were either tested negative or not tested on record. Cumulative incidences and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were computed with adjustment for competing risks. Compared to non-COVID-19 patients, both H-COVID-19 (unadjusted 19.72% vs. 3.14%, p < 0.001; aHR = 7.55 [3.33, 17.06], p < 0.001) and NH-COVID-19 (10.26% vs. 3.14%, p = 0.004; aHR = 5.08 [2.19, 11.78], p < 0.001) patients were more likely to develop new HTN. Compared to non-COVID-19 patients, both H-COVID-19 (11.41% vs. 1.14%, p < 0.001; aHR = 9.76 [4.248, 22.25], p < 0.001) and NH-COVID-19 (7.69% vs. 1.14%, p < 0.001; aHR = 6.54 [2.91, 14.67], p < 0.001) patients were more likely to develop new CKD. Compared to non-COVID-19 patients, both H-COVID-19 (4.09% vs. 1.06%, p < 0.001; aHR = 12.24 [4.09, 36.59], p < 0.001) and NH-COVID-19 (3.06% vs. 1.06%, p = 0.035; aHR = 12.94 [4.09, 40.89], p < 0.001) patients were more likely to develop new DKA at follow-up. T1D patients with COVID-19 are at higher risk of developing new HTN, CKD and DKA compared to T1D patients without COVID-19.

Brain Microvascular Pericyte Pathology Linking Alzheimer's Disease to Diabetes.

The brain microvasculature, which delivers oxygen and nutrients and forms a critical barrier protecting the central nervous system via capillaries, is deleteriously affected by both Alzheimer's disease (AD) and type 2 diabetes (T2D). T2D patients have an increased risk of developing AD, suggesting potentially related microvascular pathological mechanisms. Pericytes are an ideal cell type to study for functional links between AD and T2D. These specialized capillary-enwrapping cells regulate capillary density, lumen diameter, and blood flow. Pericytes also maintain endothelial tight junctions to ensure blood-brain barrier integrity, modulation of immune cell extravasation, and clearance of toxins. Changes in these phenomena have been observed in both AD and T2D, implicating "pericyte pathology" as a common feature of AD and T2D. This review examines the mechanisms of AD and T2D from the perspective of the brain microvasculature, highlighting how pericyte pathology contributes to both diseases. Our review identifies voids in understanding how AD and T2D negatively impact the brain microvasculature and suggests future studies to examine the intersections of these diseases.

Importance of Studying Non-Coding RNA in Children and Adolescents with Type 1 Diabetes.

Type 1 diabetes (T1D) mellitus is a chronic illness in children and teens, with rising global incidence rates. It stems from an autoimmune attack on pancreatic β cells, leading to insufficient insulin production. Genetic susceptibility and environmental triggers initiate this process. Early detection is possible by identifying multiple autoantibodies, which aids in predicting future T1D development. A new staging system highlights T1D's onset with islet autoimmunity rather than symptoms. Family members of T1D patients face a significantly increased risk of T1D. Italy recently passed a law mandating national T1D screening for pediatric populations. Measurements of β cell function continue to be essential in assessing efficacy, and different models have been proposed, but more appropriate biomarkers are mandatory for both progression studies before the onset of diabetes and during therapeutic monitoring. Biomarkers like microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) play key roles in T1D pathogenesis by regulating gene expression. Understanding their roles offers insights into T1D mechanisms and potential therapeutic targets. In this review, we summarized recent progress in the roles of some non-coding RNAs (ncRNAs) in the pathogenesis of T1D, with particular attention to miRNAs, lncRNAs, and circRNAs.

Serum Uric Acid and Microalbuminuria: Predictors of Renal Dysfunction in Type 2 Diabetes Patients in South-Western Uganda.

Background Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by insulin resistance and high blood glucose levels, which has become a global pandemic in recent decades and is associated with several health complications, including renal dysfunction. Serum uric acid levels are associated with kidney damage and have been linked to various health conditions. Urine microalbumin is a sensitive marker of kidney damage and is commonly used to monitor renal dysfunction in diabetes. The study aimed to compare the predictive value of serum uric acid and urine microalbumin in detecting kidney damage among T2D patients. Method This secondary data analysis used a cross-sectional dataset of 140 diabetic patients from Mbarara Regional Referral Hospital(MRRH) in Mbarara, Uganda. The main outcome was renal dysfunction, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m². Key variables included serum uric acid, urinary microalbumin, and various demographic and clinical factors. Data were analyzed using logistic regression and receiver operating characteristic (ROC) curve analysis to evaluate predictive performance. Ethics approval was obtained from the Mbarara University Research Ethics Committee. Results This study involved 140 participants with a median age of 53 years (interquartile range (IQR) 44-60.5), predominantly females (95, 67.9%), primarily educated (76, 54.3%), and mostly married (104, 74.3%). Participants with renal dysfunction were older (median age 61 years, IQR 52-69) compared to those without (median age 49, IQR 40-56), with significant differences in urinary microalbumin and serum uric acid levels (p <0.05). Renal dysfunction prevalence was 33.6% (95% CI: 26.2-41.9), higher in participants with diabetes duration ≥5 years, microalbuminuria, certain marital statuses, and higher diastolic blood pressure. Microalbuminuria (adjusted odds ratio (aOR) 4.71, 95% CI: 1.27-17.50, P = 0.021) and serum uric acid (aOR 1.01, 95% CI: 1.0002-1.0153, P = 0.045) were significantly associated with renal dysfunction. Other associated factors included age, female gender, and diastolic hypertension. Both biomarkers had significant predictive power for renal dysfunction (area under the curve (AUC) 0.62 and 0.65, respectively). Conclusion This study confirms the high prevalence of renal dysfunction among T2D patients, with a finding of 33.6%. The significant association between microalbuminuria and renal dysfunction, as well as the predictive capacity of serum uric acid and urinary microalbumin, highlight the importance of these biomarkers in identifying individuals at risk of kidney complications.

Enzymatic and Non-enzymatic Collagen Cross-Links and Fracture Occurrence in Type 1 Diabetes Patients.

Increased fracture risk in type 1 diabetes (T1D) patients is not fully captured by bone mineral density (BMD) by DXA. Advanced glycation end-products (AGEs) have been implicated in the increased fracture risk in T1D, yet recent publications question this. To test the hypothesis that enzymatic collagen cross-links rather than AGEs correlate with fracture incidence in T1D, we analyzed iliac crest biopsies from sex-matched, fracturing T1D patients (N = 5; T1DFx), 6 non-fracturing T1D patients (T1DNoFx), and 6 healthy subjects, by Raman microspectroscopy as a function of tissue age (based on double fluorescent labels), in intracortical and trabecular bone, to determine pyridinoline (Pyd), ε-N-Carboxymethyl-L-lysine, and pentosidine (PEN)). There were no differences in the clinical characteristics between the T1DFx and T1DNoFx groups. At trabecular forming surfaces, T1DFx patients had higher PEN and Pyd content compared to T1DNoFx ones. Previous studies have shown that elevated PEN does not necessarily correlate with fracture incidence in postmenopausal, long-term T1D patients. On the other hand, the elevated Pyd content in the T1DFx patients would be consistent with published studies showing a significant correlation between elevated trivalent enzymatic collagen cross-links and fracture occurrence independent of BMD. Collagen fibers with high Pyd content are more brittle. Thus, a plausible suggestion is that it is the enzymatic collagen cross-links that either by themselves or in combination with the adverse effects of increased AGE accumulation that result in fragility fracture in T1D.

Evaluating the Cost-Utility of Continuous Glucose Monitoring in Individuals with Type 1 Diabetes: A Systematic Review of the Methods and Quality of Studies Using Decision Models or Empirical Data.

This review presents a critical appraisal of differences in the methodologies and quality of model-based and empirical data-based cost-utility studies on continuous glucose monitoring (CGM) in type 1 diabetes (T1D) populations. It identifies key limitations and challenges in health economic evaluations on CGM and opportunities for their improvement. The review and its documentation adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. Searches for articles published between January 2000 and January 2023 were conducted using the MEDLINE, Embase, Web of Science, Cochrane Library, and Econlit databases. Published studies using models and empirical data to evaluate the cost utility of all CGM devices used by T1D patients were included in the search. Two authors independently extracted data on interventions, populations, model settings (e.g., perspectives and time horizons), model types and structures, clinical outcomes used to populate the model, validation, and uncertainty analyses. They subsequently met to confirm consensus. Quality was assessed using the Philips checklist for model-based studies and the Consensus Health Economic Criteria(CHEC) checklist for empirical studies. Model validation was assessed using the Assessment of the Validation Status of Health-Economicdecision models (AdViSHE) checklist. The extracted data were used to generate summary tables and figures. The study protocol is registered with PROSPERO (CRD42023391284). In total, 34 studies satisfied the selection criteria, two of which only used empirical data. The remaining 32 studies applied 10 different models, with a substantial majority adopting the CORE Diabetes Model. Model-based studies often lacked transparency, as their assumptions regarding the extrapolation of treatment effects beyond available evidence from clinical studies and the selection and processing of the input data were not explicitly stated. Initial scores for disagreements concerning checklists were relatively high, especially for the Philips checklist. Following their resolution, overall quality scores were moderate at 56%, whereas model validation scores were mixed. Strikingly, costing approaches differed widely across studies, resulting in little consistency in the elements included in intervention costs. The overall quality of studies evaluating CGM was moderate. Potential areas of improvement include developing systematic approaches for data selection, improving uncertainty analyses, clearer reporting, and explaining choices for particular modeling approaches. Few studies provided the assurance that all relevant and feasible options had been compared, which is required by decision makers, especially for rapidly evolving technologies such as CGM and insulin administration. High scores for disagreements indicated that several checklists contained questions that were difficult to interpret consistently for quality assessment. Therefore, simpler but comprehensive quality checklists may be needed for model-based health economic evaluation studies.

Improved Clinical Outcomes with the Combination Therapy of a Glucagon-like Peptide-1 Receptor Agonists and a Sodium-glucose Cotransporter-2 Inhibitor in Overweight/Obese People with Type 2 Diabetes: Real-world Evidence from the Indian Subcontinent.

Type 2 diabetes (T2D) mellitus is increasing exponentially in India, with overweight/obesity being prime contributors. This study aimed at assessing the clinical impact of the combination therapy of a glucagon-like peptide-1 receptor agonist (GLP-1RA) injection (inj.) and a sodium-glucose cotransporter-2 inhibitor (SGLT-2i) in overweight/obese patients from the Indian subcontinent. In two real-world evidence (RWE) studies (RWE1 and 2), we retrospectively observed the effect of the combination therapy of a GLP-1RA, injection dulaglutide (DU) 1.5 mg/week, and an SGLT-2i, canagliflozin (CAN) 100 mg/day at weeks 16, 32, and 52 on HbA1c, body weight (weight), systolic blood pressure (SBP), lipids, change in doses of antidiabetic agents (ADA) and antihypertensive agents (AHA) in overweight/obese Asian Indian subjects with T2D, who had suboptimal glycemic control. A total of 95 T2D patients [51 males (M), 44 females (F)] completed the two RWE studies. In RWE 1, 40 patients (20 M/20 F), mean [standard deviation (SD)] age 49.4 (10.7) years (Y), weight 92.6 (6.6) kg, body mass index (BMI) 30.6 (2.3) kg/m2, duration of T2D 8.1 (3.2) Y, completed the study. At week 32, the mean (SD) reduction in A1c (%) was -1.3% [8.4 (0.7) to 7.1 (0.3); p < 0.01] and mean (SD) weight (kg) loss was -5.5 [92.6 (6.6) to 87.9 (7.02); p < 0.00001]. This group was then followed up until week 52. In RWE 2, 55 patients (31 M/24 F), age 51 (5.8) Y, weight 92.6 ± 3.4 kg, BMI 31.1 ± 2.1 kg/m2, SBP 142.4 ± 3.9 mm Hg, estimated glomerular filtration rate (eGFR) 62 ± 5 mL/minute/1.73 m2, with 8.4 ± 3.3 Y duration of diabetes met the inclusion criteria. In 71% of subjects, A1c decreased by -1.4% [8.5 ± 0.4 to 7.1 ± 0.2; p < 0.0001] at week 16 and was 6.8 ± 0.3 (p = 0.0002) in 18% at week 32. A statistically significant (SS) improvement in glycemic control, weight, and improvement in cardiovascular (CV) risk factors was observed with the GLP-1RA/SGLT-2i combination, which was well tolerated.

Triglyceride-Glucose Index Levels Positively Associated with Higher Risk of Low Muscle Mass in Patients with Type 2 Diabetes.

Although the interplay of insulin resistance (IR) and low muscle mass is increasingly recognized, it remains unknown whether the triglyceride-glucose (TyG) index, as an indicator of IR, is associated with low muscle mass in patients with type 2 diabetes (T2D). Our study aimed to investigate the association between TyG index and low muscle mass in hospitalized T2D patients. This cross-sectional study involved 2687 hospitalized participants with T2D. The TyG index was calculated by fasting plasma glucose (FPG) and triglyceride levels. The outcome variables were defined as appendicular skeletal muscle mass index (ASMI) and low muscle mass. To explore the relationship between TyG index and low muscle mass, we conducted the multivariate linear regression, multivariate logistic regression, and subgroup analysis. In the fully adjusted multivariate linear regression, there was a negative correlation between TyG index (β=-0.10, 95% CI: -0.14, -0.06) and ASMI. TyG index (OR = 1.34, 95% CI: 1.08, 1.65) had a more significant association with low muscle mass compared to FPG (OR = 1.05, 95% CI: 1.01, 1.09) and glycated hemoglobin A1c (OR = 1.07, 95% CI: 0.99, 1.15). The statistical significance of the trend persisted among the TyG index quartile groups. Subgroup analysis revealed stronger positive associations between TyG index and low muscle mass in females, individuals aged 60 years or older, those with a body mass index of 28kg/m2 or higher, and HbA1c levels of 6.5% or higher, as well as those with hypertension and dyslipidemia. A higher TyG index level is positively associated with a higher risk of low muscle mass, suggesting that TyG index could be a potential biomarker of low muscle mass in hospitalized T2D patients.

Association of overexpression of PLD6, CHRAC1 and PDCD5 with type 2 diabetes mellitus

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim &amp;lt;/strong&amp;gt;Diabetes type 2 (DT2) is a metabolic disease characterized by high blood sugar caused by insulin resistance and/or insufficient insulin production. The pathogenesis of DT2 is complicated by both genetic predisposition and environmental and lifestyle variables. At least 150 genetic variants have been linked to the probability of having DT2. The aim of this study was to determine the expression of PLD6, CHRAC1, and PDCD5 genes in type 2 diabetic patients.&amp;amp;nbsp;&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods &amp;lt;/strong&amp;gt;Information on 12 DT2 patients was obtained from the Gene Expression Omnibus (GEO) using the series identification (ID) (GSE34008). The analysis tools GEO2R, String Utils (STRING), University of Alabama at Birmingham Cancer data analysis (UAL-CAN), and the Cancer Genome Atlas (TCGA) were used. The human protein atlas provided details on gene cancer.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results &amp;lt;/strong&amp;gt;Only ten genes with expression differences ranging from low to high were selected. PLD6, CHRAC1, and PDCD5 were detected to have higher expression in patients compared to controls. The number of patients with primary pancreatic adenocarcinoma for SLC16A4, DERK2, and CHRAC1 was greater than that of healthy controls. Concerning the severity of cancer, all chosen genes demonstrated a greater proportion of affected individuals compared to the control group.&amp;amp;nbsp;&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion &amp;lt;/strong&amp;gt;There are multiple genes whose increased expression is linked to type 2 diabetes.&amp;lt;/p&amp;gt;

P191 CO-EXISTING HYPERTENSION: AN INDEPENDENT RISK FACTOR FOR DIABETIC RETINOPATHY IN TYPE-2 DIABETES

Background and Objectives: Hypertension has plausible reason to be show the interaction due to its independent effect on retina. Epidemiological studies also provide clue that for hypertension as a possible effect modifier in the risk development of retinopathy in diabetic patients. It is worth exploring whether subgroup in diabetic population with Hypertension have different risk potential of developing retinopathy. The present study aimed to assess the association of hypertension as a risk factor for diabetic retinopathy (DR) in type 2 diabetes mellitus. Methods: A total of 977 type-2 diabetic patients recruited retrospectively in 2008 from Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorder (BIRDEM) based on hospital records for determining the incidence of diabetic retinopathy (DR), who were naı̈ve type-2 diabetes during 1993. At the end of 15 year follow-up 495 patients were diagnosed as DR by retinal colour photography. Data on diabetes and lipid profile with serum creatinine, blood pressure and biophysical measures were obtained at baseline, 5, 10 and 15 years follow-up. Binary logistic regression model was used to assess the associations of co-existing hypertension with retinopathy risk adjusting for clinical, biochemical and anthropometric variables. Results: In all three follow-up points, including at baseline, mean systolic and diastolic blood pressure were found to significantly higher among patients who developed DR (P&lt;.001). Binary logistic regression model confirmed coexisting hypertension (OR 3.2; 95% CI 2.2 -4.7) as a significant risk factor of DR adjusting for possible confounders; serum creatinine (OR 21.9; 95% CI 14.0 -35.4) and glycemic control status (OR 17.2; 95% CI 9.4 -31.4). Interaction between hypertension, glycemic control and raised serum creatinine did not appear to be statistically significant (P&gt;0.05). Conclusions: Co-existing hypertension is a significant risk factor of DR irrespective of nephropathy or glycolic control status among Type 2 diabetes mellitus.

Generalizability and treatment with sodium-glucose co-trasporter-2 inhibitors (SGLT2i) among patients with type 2 diabetes: an assessment using an Italian primary care database.

This study aimed to assess the proportions of type 2 diabetes (T2D) subjects meeting cardiovascular outcome trials (CVOTs) criteria for sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and estimate SGLT2i utilization, along with associated demographic and clinical characteristics, in a primary care setting. T2D patients in Italy were selected between January 1, 2021, and December 31, 2022, from The Health Improvement Network (THIN®) database. Representativeness was determined by dividing patients meeting key inclusion criteria for four CVOTs (CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, VERTIS-CV) to the total T2D population. Demographic and clinical characteristics of eligible T2D subjects and SGLT2i users were compared, and logistic regression models assessed the likelihood of receiving SGLT2i. Out of 17,102 T2D patients, 8,828 met eligibility criteria for at least one CVOT. DECLARE-TIMI 58 exhibited the highest representativeness (51.1%), compared to CANVAS (21.1%), EMPA-REG OUTCOME (5.5%), and VERTIS-CV (4.9%) trials. Eligible CVOTs patients were older (74.6 vs. 68.3 years), with a longer disease duration (10.2 vs. 9.7 years), and higher established cardiovascular disease (CVD) prevalence (36.0 vs. 27.3%) compared to SGLT2i users. Less than 10% of eligible T2D patients received SGLT2i. Males (OR: 1.43; 95%CI: 1.24-1.66) were more likely to be prescribed SGLT2i than other antidiabetic drugs, while the elderly (80 + vs. 40-64 years, OR: 0.17; 95% CI: 0.14-0.22) were less likely. Eligible T2D patients with CVD reported an increased likelihood of receiving SGLT2is compared to other antidiabetics. This study highlights significant variability in the proportion of T2D subjects meeting SGLT2i CVOT inclusion criteria, with DECLARE-TIMI-58 being the most represented. Low SGLT2i prescription rates in the Italian primary care setting, along with substantial demographic and clinical differences between SGLT-2i users and T2D eligible patients, emphasize the need for targeted interventions to optimize the use of these medications in primary care settings.

Optimizing physician-encounter frequency for type 2 diabetes patients in primary care based on cardiovascular risk assessment: A target trial emulation study.

To investigate whether the physician-encounter interval for patients with type 2 diabetes (T2D) can be optimized from 2-3 to 4-6 months among those with a calculated 10-year cardiovascular disease (CVD) risk score of less than 20% without compromising their long-term outcomes. Using territory-wide public electronic medical records in Hong Kong, we emulated a target trial to compare the effectiveness of the physician-encounter intervals of 4-6 versus 2-3 months for T2D patients without prior CVDs and with a predicted risk for CVDs of less than 20% (i.e. those patients not in the high-risk category). Propensity score matching was used to emulate the randomization of participants at baseline, where 42 154 matched individuals were included for analysis. The marginal structural model was applied to estimate the hazard ratio (HR) for CVD incidence and all-cause mortality, the incidence rate ratio of secondary and tertiary care utilization, as well as the between-group differences in HbA1c, blood pressure and cholesterol levels. During a follow-up period of up to 12 (average: 5.1) years, there was no significantly increased risk of CVD in patients with physician-encounter intervals of 4-6 months compared with those patients with physician-encounter intervals of 2-3 months (HR [95% confidence interval {CI}]: 1.01 [0.90, 1.14]; standardized 10-year risk difference [95% CI]: -0.1% [-0.7%, 0.6%]), nor for all-cause mortality (HR: 1.00 [0.84, 1.20]; standardized 10-year risk difference: -0.1% [-0.5%, 0.3%]). Additionally, there was no observable difference in the utilization of secondary and tertiary care or key clinical parameters between these two follow-up frequencies. For T2D patients with a calculated 10-year CVD risk of less than 20%, the interval of regular physician encounters can be optimized from 2-3 to 4-6 months without compromising patients' long-term outcomes and saving substantial service resources in primary care.

Islet amyloid polypeptide fibril catalyzes amyloid-β aggregation by promoting fibril nucleation rather than direct axial growth

Aberrant aggregation of amyloid-β (Aβ) and islet amyloid polypeptide (IAPP) into amyloid fibrils underlies the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes (T2D), respectively. T2D significantly increases AD risk, with evidence suggesting that IAPP and Aβ co-aggregation and cross-seeding might contribute to the cross-talk between two diseases. Experimentally, preformed IAPP fibril seeds can accelerate Aβ aggregation, though the cross-seeding mechanism remains elusive. Here, we computationally demonstrated that Aβ monomer preferred to bind to the elongation ends of preformed IAPP fibrils. However, due to sequence mismatch, the Aβ monomer could not directly grow onto IAPP fibrils by forming multiple stable β-sheets with the exposed IAPP peptides. Conversely, in our control simulations of self-seeding, the Aβ monomer could axially grow on the Aβ fibril, forming parallel in-register β-sheets. Additionally, we showed that the IAPP fibril could catalyze Aβ fibril nucleation by promoting the formation of parallel in-register β-sheets in the C-terminus between bound Aβ peptides. This study enhances our understanding of the molecular interplay between Aβ and IAPP, shedding light on the cross-seeding mechanisms potentially linking T2D and AD. Our findings also underscore the importance of clearing IAPP deposits in T2D patients to mitigate AD risk.

Okinawa-Based Nordic Diet Decreases Plasma Glial Fibrillary Acidic Protein Levels in Type 2 Diabetes Patients.

Elevated levels of glial fibrillary acidic protein (GFAP) in plasma reflect neuroinflammation and are linked to cognitive decline. Preclinical studies show that dietary change can attenuate astrocyte reactivity and neuroinflammation. In the current study, we investigate if the Okinawa-based Nordic (O-BN) diet alters plasma GFAP levels in patients with Type 2 Diabetes (T2D), a metabolic disorder associated with cognitive disturbances and an increased risk of dementia. Plasma GFAP levels were measured in T2D patients (n = 30) at baseline, after 3 months of the diet, and after a subsequent 4 months of unrestricted diets. The GFAP levels decreased significantly after 3 months of the diet (p = 0.048) but reverted to baseline levels after 4 months of unrestricted diets. At baseline, the GFAP levels correlated significantly with levels of the neurodegeneration marker neurofilament light polypeptide (r = 0.400*) and, after correcting for age, sex, and body mass index, with proinflammatory plasma cytokines (ranging from r = 0.440* to r = 0.530**) and the metabolic hormone islet amyloid polypeptide (r = 0.478*). We found no correlation with psychological well-being. These results suggest that the O-BN diet reduces neuroinflammation in T2D patients and may thus be an important preventive measure for managing T2D and reducing the risk of neurodegenerative disorders.

Psychometrics properties of type 2 diabetes treatment adherence questionnaire (DTAQ): a study based on Pender’s health promotion model

BackgroundManagement of type 2 diabetes (T2D) as a chronic disease requires treatment adherence such as controlling the blood glucose level and adopting a healthy lifestyle. The present study aimed to develop and psychometrically evaluate a questionnaire based on the Pender’s Health Promotion Model (HPM) to measure treatment adherence and the associated factors among T2D patients.MethodsThe present study was conducted in qualitative and the quantitative phases between March 2022 and March 2023. The participants were T2D patients visiting Shahid Mohammadi hospital Diabetes Clinic in Bandar Abbas in the south of Iran. The first draft of items was extracted from the qualitative phase. The present study used interviews with T2D patients, item construction, validity and reliability evaluation of the instrument, and the relevant statistical analyses. It emphasized the significance of content, face, and construct validity, along with reliability testing using Cronbach’s alpha and test-retest method. Data were analyzed using SPSS software, V16 and AMOS, V23.ResultsA 97-item questionnaire was developed through the qualitative phase and, after content validity, it was reduced to 86 items. Five items were removed in face validation, and after the test-retest method, 79 items were retained. The confirmatory factors analysis confirmed a 65-item model with appropriate fitness of data. Cronbach’s alpha coefficient showed an acceptable reliability of the diabetes treatment adherence questionnaire (α = 0.92).ConclusionThe questionnaire developed based on the HPM model provides a standard and comprehensive measurement of the degree of adherence to treatment and the associated factors among Iranian T2D patients. This is especially valuable in the Iranian healthcare context, where effective management of chronic diseases such as diabetes is of a top priority. Questionnaires can help identify barriers and facilitators of treatment adherence to inform systematic and goal-oriented interventions. The proposed questionnaire had good psychometric properties, and can be used as a valid and practical instrument to measure the factors related to treatment adherence behaviors.

KIR2DL5+CD8+ T cells associate with dietary lipid intake and are active in type 1 diabetes

BackgroundRecent studies have shown that KIR+CD8+ T cells play a role in suppressing autoimmunity by eliminating pathogenic CD4+ T cells. However, their specific role in type 1 diabetes (T1D) remains unclear. MethodsIn this study, we enrolled 108 patients diagnosed with T1D and 86 healthy individuals. We conducted flow cytometric analysis to examine the various subtypes of KIR+CD8+ T cells derived from peripheral blood mononuclear cells. Additionally, CD8+ T cells were isolated from the peripheral blood of T1D patients to assess the functions of different KIR+CD8+ T cell subtypes. To investigate the influence of lipids on the characteristics and activities of these T cell subtypes, the isolated CD8+ T cells were cultured with varying concentrations of palmitic acid (PA). Furthermore, we utilized an NSG (NOD scid gamma) mouse adoptive transfer model to assess the impact of dietary lipid intake on the functionality of KIR2DL5+CD8+ T cells in vivo. ResultsWe observed variations in circulating KIR+CD8+ T cell subtypes between patients with T1D and healthy controls. Notably, we observed a significant negative correlation between the frequencies of circulating KIR+CD8+ T cells and the titers of ZnT8 autoantibodies in individuals with T1D. Among these subtypes, KIR2DL5+CD8+ T cells demonstrated a positive association with dietary fat intake, characterized by increased perforin expression and reduced PD-1 expression. Importantly, KIR2DL5+CD8+ T cells exhibited enhanced proliferative capacity compared to other KIR+CD8+ T cell subsets. Palmitic acid (PA) was found to enhance the activation of KIR2DL5+CD8+ T cells and strengthened their ability to suppress CD4+ T cell proliferation in T1D patients. Moreover, dietary lipid intake significantly enhanced the functionality of KIR2DL5+CD8+ T cells in an NSG mouse adoptive transfer model. ConclusionOur findings suggest that lipid intake enhances the functionality of human KIR2DL5+CD8+ T cells and may offer implications for immunotherapy in T1D.

The microbiota-dependent tryptophan metabolite alleviates high-fat diet–induced insulin resistance through the hepatic AhR/TSC2/mTORC1 axis

Type 2 diabetes (T2D) is potentially linked to disordered tryptophan metabolism that attributes to the intricate interplay among diet, gut microbiota, and host physiology. However, underlying mechanisms are substantially unknown. Comparing the gut microbiome and metabolome differences in mice fed a normal diet (ND) and high-fat diet (HFD), we uncover that the gut microbiota-dependent tryptophan metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) is present at lower concentrations in mice with versus without insulin resistance. We further demonstrate that the microbial transformation of tryptophan into 5-HIAA is mediated by Burkholderia spp. Additionally, we show that the administration of 5-HIAA improves glucose intolerance and obesity in HFD-fed mice, while preserving hepatic insulin sensitivity. Mechanistically, 5-HIAA promotes hepatic insulin signaling by directly activating AhR, which stimulates TSC2 transcription and thus inhibits mTORC1 signaling. Moreover, T2D patients exhibit decreased fecal levels of 5-HIAA. Our findings identify a noncanonical pathway of microbially producing 5-HIAA from tryptophan and indicate that 5-HIAA might alleviate the pathogenesis of T2D.

Bidirectional association between type 2 diabetes and irritable bowel syndrome: A large-scale prospective cohort study.

To examine the bidirectional association between type 2 diabetes (T2D) and irritable bowel syndrome (IBS) in a large prospective population cohort. Participants free of IBS at baseline in the UK Biobank were included in the analysis of T2D and incident IBS (cohort 1), with 11 140 T2D patients and 413 979 non-T2D patients. Similarly, those free of T2D at baseline were included in the analysis of IBS and incident T2D (cohort 2), with 21 944 IBS patients and 413 979 non-IBS patients. Diagnoses of T2D and IBS were based on International Classification of Disease-10 codes. The Cox proportional hazards model was used to estimate adjusted hazard ratios (HRs). In cohort 1, 8984 IBS cases were identified during a median 14.5-year follow-up. Compared with non-T2D, T2D patients had a 39.0% increased risk of incident IBS (HR = 1.39, 95% confidence interval [CI]: 1.23-1.56, P < .001), with a higher IBS risk in those with higher fasting blood glucose levels (HR = 1.43, 95% CI: 1.19-1.72, P < .001) or longer T2D duration (HR = 1.47, 95% CI: 1.23-1.74, P < .001). In cohort 2, 29 563 incident T2D cases were identified. IBS patients had an 18.0% higher risk of developing T2D versus non-IBS patients (HR = 1.18, 95% CI: 1.12-1.24, P < .001). A similar excess T2D risk was observed in IBS patients with a duration of either less than 10 years, or of 10 years or longer. Further sensitivity analysis and subgroup analysis indicated consistent findings. T2D and IBS exhibit a bidirectional association, with an increased risk of co-morbidity. Awareness of this association may improve the prevention and management of both diseases.

Periphery Biomarkers Predicting Conversion of Type 2 Diabetes to Pre-Alzheimer-Like Cognitive Decline: A Multicenter Follow-Up Study.

The prevalence of Alzheimer's disease (AD) is increasing, therefore, identifying biomarkers to predict those vulnerable to AD is imperative. Type 2 diabetes (T2D) serves as an independent risk factor for AD. Early prediction of T2D patients who may be more susceptible to AD, so as to achieve early intervention, is of great significance to reduce the prevalence of AD. To establish periphery biomarkers that could predict conversion of T2D into pre-AD-like cognitive decline. A follow-up study was carried out from 159 T2D patients at baseline. The correlations of cognitive states (by MMSE score) with multi-periphery biomarkers, including APOE genotype, plasma amyloid-β level, platelet GSK-3β activity, and olfactory score were analyzed by logistic regression. ROC curve was used for establishing the prediction model. Additionally, MRI acquired from 38 T2D patients for analyzing the correlation among cognitive function, biomarkers and brain structure. Compared with the patients who maintained normal cognitive functions during the follow-up period, the patients who developed MCI showed worse olfactory function, higher platelet GSK-3β activity, and higher plasma Aβ42/Aβ40 ratio. We conducted a predictive model which T2D patients had more chance of suffering from pre-AD-like cognitive decline. The MRI data revealed MMSE scores were positively correlated with brain structures. However, platelet GSK-3β activity was negatively correlated with brain structures. Elevated platelet GSK-3β activity and plasma Aβ42/Aβ40 ratio with reduced olfactory function are correlated with pre-AD-like cognitive decline in T2D patients, which used for predicting which T2D patients will convert into pre-AD-like cognitive decline in very early stage.