Risk Of Type 2 Diabetes Mellitus Research Articles

Dependent censoring bias assessment using inverse probability of censoring weights: Type 2 diabetes mellitus risk in patients initiating bisoprolol versus other antihypertensives in a Clinical Practice Research Datalink cohort study.

Dependent censoring involves a preferential attrition of a subgroup of interest; occurring in survival analysis, it may impact interpretation by introducing a selection bias. To assess the potential bias in a comparison of bisoprolol to other antihypertensives in terms of Type 2 diabetes mellitus (T2DM) incidence, inverse probability of censoring weights (IPCW) was used. It was further used to contextualize results obtained through competing risks analysis. Two estimands were considered to assess T2DM incidence while accounting for deviations from the initial antihypertensive monotherapy (DFM). A hypothetical estimand using IPCW, treating DFM as censoring, was interpreted together with a 'while-on-treatment' estimand, treating DFM as a competing risk. We illustrated our application with a cohort study based on Clinical Practice Research Datalink (CPRD) including 267,352 patients with newly diagnosed arterial hypertension between 2000 and 2017, initiating antihypertensive monotherapy among bisoprolol, other beta-blockers, renin-angiotensin system drugs (ACEi/ARB), diuretics and calcium-channel blockers. A mild dependent censoring process was hypothesized, leading to slight overestimation of T2DM incidence. Although subject to some limitations, a nonsignificant trend toward an excess of risk associated with ACEi/ARB was yielded consistently by IPCW and competing risks analyses. Conversely, in comparisons of bisoprolol versus either diuretics, other beta-blockers or calcium channel blockers, no significant differences or critical dependent censoring impact were found. Concurrent use of complementary estimands allowed formulating a refined interpretation of our findings: though not significant, the trend toward an excess of T2DM risk associated with a ACEi/ARB monotherapy compared with bisoprolol is likely not originating only from the minor dependent censoring. Reassessing identical estimands in other cohorts would provide insights to corroborate or refute this result.

Association Between Nontraditional Lipid Profiles and the Risk of Type 2 Diabetes Mellitus in Chinese Adults With Hypertension: Findings From the China Hypertension Registry Study.

The relationship between nontraditional lipid profiles and type 2 diabetes mellitus (T2DM) remains ambiguous within the hypertension population. The objective of this study is to examine the association between nontraditional lipid profiles and T2DM in Chinese adults with hypertension. The current investigation encompassed 13728 participants with hypertension from the China Hypertension Registry Study. Logistic regression analysis and smooth curve fitting were employed to evaluate the association between nontraditional lipid profiles and T2DM. The prevalence of T2DM was found to be 17.8%. In the fully adjusted model, atherogenic index of plasma (AIP) exhibited the highest odds ratios (ORs) for T2DM (OR: 2.71, 95% confidence interval [CI]: 2.26-3.26). Conversely, the fully adjusted ORs (95% CI) for total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)/HDL-C, and non-high-density lipoprotein cholesterol (Non-HDL-C) were 1.33 (1.25-1.41), 1.40 (1.29-1.51), and 1.41 (1.34-1.49), respectively. Additionally, the study demonstrated that AIP had a superior ability to identify T2DM. Subgroup analyses indicated that the relationship between AIP and Non-HDL-C with T2DM was more significant in the lighter weight population. In addition, the association of TC/HDL-C with LDL-C/HDL-C with T2DM was stronger in the lower homocysteine level population. Among the southern Chinese population with hypertension, all nontraditional lipid indices positively correlated with the risk of T2DM. Among these lipid indices, AIP exhibited superior discriminatory power in identifying T2DM compared to TC/HDL-C, LDL-C/HDL-C. Trial Registration: ChiCTR1800017274.

Exploring Risk Factors of Type 2 Diabetes Mellitus Using Decision Tree and Random Forest Models: Baseline Data From Kharameh Cohort Study

Background and aims: Identifying subjects that are at risk of type 2 diabetes mellitus (T2DM) and predicting the associated risk factors are highly important. Thus, this study aimed to explore the risk factors and find the prediction model for T2DM using decision trees (DTs) and random forest (RF) models. Methods: This cross-sectional study is a part of the Kharameh Cohort Study. Kharameh Cohort is a part of the Fars Cohort, which started in 2014 with 10663 people aged 40–70. In this study, the risk factors of T2DM were explored using two data mining methods. Accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were applied to evaluate the models. The data were statistically analyzed using R software. Results: The DT modeling showed that age, triglycerides (TG), physical activity, systolic blood pressure, low-density lipoproteins (LDL), and body mass index (BMI) were the most associated factors in D2MT, while applying RF revealed that fasting blood sugar, cholesterol, creatinine, TG, gamma-glutamyl transferase physical activity, BMI, and LDL were the most effective on T2DM. The RF model was superior to the DT based on the applied criteria. Sensitivity, specificity, accuracy, and AUC for the RF were 73.4, 70.10, 73.5, and 79.1. These findings for the DT were 63.8, 69.7, 62.8, and 66.8, respectively. Conclusion: Based on the inferences, a strong association was found between several risk factors and the risk of T2DM. Therefore, predictive analytics using the RF model can be applied to identify the risk factors of other chronic diseases.

Targeting the cholinergic anti-inflammatory pathway for type 2 diabetes prevention: A retrospective cohort study.

Chronic inflammation is a key factor in type 2 diabetes mellitus (T2DM) development. The cholinergic anti-inflammatory pathway (CAP) reduces inflammation by activating α7 nicotinic acetylcholine receptors (α7nAChRs) on macrophages, suppressing proinflammatory cytokines. Acetylcholinesterase inhibitors (AChEis), primarily used for Alzheimer's disease (AD), may exert anti-inflammatory effects through the CAP. One AChEi, galantamine, also directly agonizes α7nAChRs, potentially enhancing its anti-inflammatory properties. This study aimed to investigate the association between AChEi use, particularly galantamine, and T2DM risk in AD patients. We conducted a retrospective analysis of Veterans Health Administration (VA) data, examining early- and late-onset AD patients receiving galantamine or other AD medications. Propensity score matching was used to balance groups and minimize confounding. Cox proportional hazard models assessed T2DM risk for galantamine, other AChEis and memantine. A total of 40 065 AD patients were included in the study. Among early-onset AD patients, galantamine use significantly reduced T2DM risk (hazard ratio [HR] = 0.80, 95% confidence interval [CI]: 0.66-0.98). Memantine also showed a protective effect (HR = 0.82, 95% CI: 0.69-1) in this group. Neither galantamine nor memantine influenced T2DM risk in late-onset AD. Other AD medications showed no association with T2DM risk. Galantamine use was associated with a lower risk of T2DM in early-onset AD patients, potentially due to enhanced anti-inflammatory effects through both AChE inhibition and direct α7nAChR agonism. Memantine also demonstrated a protective effect. These findings suggest potential new applications for existing AD medications in T2DM prevention, particularly in early-onset AD patients. Further research, including randomized controlled trials with diverse populations, is needed to confirm these results and the underlying mechanisms.

The Relationship between Dietary Habits and Type 2 Diabetes for Contribution to Health Promotion: Literature Review

Introduction: Type 2 Diabetes Mellitus (T2DM) is a chronic condition largely influenced by dietary habits and eating behaviors. Poor dietary choices, such as high consumption of refined sugars, unhealthy fats, and low intake of fiber, are well-established risk factors for the development of T2DM. The promotion of healthy eating behaviours and active lifestyles is essential to address the increasing prevalence of T2DM and improve public health. Objective: This study aimed to examine the impact of various dietary patterns and specific food intakes on the risk of T2DM, as well as the role of meal timing and dietary quality in influencing blood glucose levels and insulin sensitivity. Method: This research employs a literature review method by analyzing several relevant studies. The articles were sourced from Scopus and Google Scholar, using keywords such as "feeding behavior," "eating behavior," "feeding patterns," "food habits," "dietary habits," and "type 2 Diabetes," "diabetes Type 2," "type 2 diabetes mellitus," "diabetes mellitus type 2," and "T2DM." Result: The results of the article search revealed 13 articles from 2019-2024 that matched the criteria set. The results showed that Eating habits have a significant effect on the risk of developing Type 2 Diabetes Mellitus (T2DM). Poor food choices and irregular eating patterns increase the risk. Conclusion: The paper highlights the significant impact of dietary habits and eating behaviors on the development and progression of Type 2 Diabetes Mellitus. It emphasises the importance of healthy food choices and regular eating patterns in managing blood glucose levels and insulin sensitivity. These insights could contribute to designing an effective health promotion program.

Association between body mass index trajectories and type 2 diabetes incidence over an 18-year follow-up in the Tehran Lipid and Glucose Study.

Body mass index (BMI) is a well-known risk factor for type 2 diabetes mellitus (T2DM). We aimed to identify BMI trajectory patterns and evaluate their association with T2DM during 18 years of follow-up. We included 6026 participants aged 20 to 65 from the prospective population-based Tehran Lipid and Glucose Study (TLGS). The BMI trajectory patterns were identified using latent growth mixture modeling (LGMM) during the measurement period. The association between the BMI trajectory patterns and future T2DM was evaluated using the Cox proportional hazard regression models. Three BMI trajectory patterns of low-increasing (38.6%), medium-increasing (47.1%), and high-increasing (14.3%) were detected. The participants in the medium-increasing and high-increasing BMI trajectory groups had HRs of 1.87 (95% CI 1.53-2.28) and 3.41(95% CI 2.71-4.29) for T2DM incidence, respectively. Within the normoglycemic subpopulation, the high-increasing BMI group had an HR of 3.82 (95% CI 2.79-5.24) compared to the low-increasing BMI group, while in the prediabetic subpopulation, the high-increasing BMI group had an HR of 2.93 (95% CI 2.04-4.19) compared to the low-increasing BMI group. Body weight varies in a relatively stable pattern in adulthood over the long-term period. Medium and high-increasing BMI trajectory patterns have a significantly increased risk for future T2DM in both normoglycemic and prediabetic individuals. Identifying BMI trajectory patterns can help healthcare providers in early prediction, risk assessment, and monitoring strategies development for the prevention of T2DM.

Potassium inwardly-rectifying channel subfamily J member 11 (KCNJ11) gene polymorphism in Egyptian type 2 diabetic patients: a single-center study.

The KCNJ11 gene belongs to the potassium channel gene family. It has a major role inthe secretion of insulin. Genetic variations in KCNJ11 are possibly responsible for the progression of type 2 diabetes mellitus (T2DM). In this study, we investigated the possible correlation between KCNJ11 (rs5210) gene polymorphism and T2DM. This study included 92 individuals divided into two groups. Group 1 included 46 type 2 diabetic patients. Group 2 (control group) included 46 healthy participants. A complete history was taken and a full physical examination was performed. Anthropometric data were measured. Laboratory investigations included fasting blood glucose (FBG), two hours post-prandial blood glucose (2HPPBG), glycated hemoglobin (HbA1c), and fasting lipid profile. KCNJ11 (rs5210) single nucleotide polymorphism was detected by polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP). Both AG and GG genotypes were associated with increased risk for T2DM (OR 5.2, 95% CI 1.32-20.5, P = 0.01 for AG; and OR 18.2, 95% CI 2.99-31.7, P = 0.002 for GG). Also, the frequency of the G allele was significantly higher in type 2 diabetic patients compared to healthy controls (50% versus 23.9%, respectively). The G allele of rs5210 in KCNJ11 contributed to an increased risk of T2DM (OR 3.18, 95% CI 1.31-7.75, P = 0.01). There was a statistically significant association between increased 2HPPBG and HbA1c levels and the carrier of AG and GG genotypes (P = 0.01 and 0.007, respectively). There was a statistically significant association between total cholesterol(TC), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) levels and the carrier of AG and GG genotypes (P < 0.001, 0.02, and 0.007, respectively). Regression analysis detected that body mass index (BMI), 2HPPBG, TC, triglycerides (TG), and the G allele of rs5210 in KCNJ11 gene showed a significant association with T2DM (P = 0.004, 0.042, 0.003, 0.006, and 0.01, respectively) while no association was observed with FBG, HbA1c, LDL-c or HDL-c (P = 0.099, 0.123, 0.522, and 0.765, respectively). KCNJ11 rs5210 genetic polymorphism may raise the risk for the occurrence ofT2DM among Egyptians.

Association of intrinsic capacity with incident type 2 diabetes mellitus in older Chinese: Guangzhou Biobank Cohort Study

BackgroundThe World Health Organization introduced intrinsic capacity (IC) as a metric for healthy aging. However, we found no report on the association between IC and type 2 diabetes mellitus (T2DM). We investigated the association between IC and incident T2DM in older Chinese from the Guangzhou Biobank Cohort Study. MethodsIC was assessed across five domains equally: locomotion, vitality, cognition, psychological and sensory. Composite IC scores (0-10) were classified into three groups: poor (0-5.9), fair (6.0-8.9), and high (9.0-10), with higher scores representing greater IC. Multivariable linear regression and cox regression was used to analyze the association between IC with glycemia and T2DM, respectively. ResultsOf 3582 participants with a mean age of 59.1 years (standard deviation (SD)=7.13) without baseline diabetes, during an average follow-up of 3.3 years (SD=0.86), 497 (13.87%) developed T2DM. After adjustments for potential confounders, those with baseline poor IC, versus high, had higher fasting glucose, 2-hour post-load glucose and glycosylated hemoglobin A1c at follow-up, and a higher risk of incident T2DM (HR (95%CI): 1.80 (1.20, 2.72)). Among IC domains, only vitality impairment was associated with an increased risk of T2DM (P for trend < 0.001). ConclusionWe first reported the prospective associations of poor IC and vitality with higher glycemia and incident T2DM risk. Enhancing muscle strength to improve functional ability may be a possible intervention for reducing future risk of T2DM in older populations.

Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) dietary exposure is associated with an increased risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Aims/hypothesisThe aim of the present study was to investigate the association between dietary exposures to dioxins, dioxin-like polychlorinated biphenyls (DL-PCBs) and non-dioxin-like polychlorinated biphenyls (NDL-PCBs) and the incidence of type 2 diabetes mellitus (T2DM) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. MethodsThis prospective cohort study with a median 11.7 years of follow-up, included 318,416 individuals recruited in 21 centers in eight countries. Dietary intake of dioxins and PCBs was calculated by combining EPIC food consumption data with food contamination data from the European Food Safety Authority (EFSA). To identify incident cases of T2DM, a thorough review of various sources including self-reported information, linkage to primary and secondary care registers, drug registers, hospital admissions, and mortality data was conducted. Associations between dietary intake of dioxins and PCBs and T2DM were evaluated using multivariable Cox regressions. ResultsHigher T2DM risk was observed for higher estimated dietary intake of non-dioxin-like PCBs (NDL-PCBs; HR per 1 SD increment = 1.03 [95%CI 1.01;1.04], and HR (Q4 vs Q1) = 1.15 [1.08;1.22], P-trend < 0.001). The results were consistent in analyses stratified by gender, body mass index, country, median follow-up, or self-reported hypertension and hyperlipidemia, as well as when adjusting for fat intake. No consistent association was observed between dioxins+DL-PCBs intake and T2DM risk. Conclusion / interpretationResults obtained in this large European prospective study indicate a positive and linear association between dietary intake of NDL-PCBs and risk of T2DM. This association remained consistent across various stratified and sensitivity analyses. Further studies are warranted to better understand the biological mechanisms underlying this association.

The association between parity and type 2 diabetes mellitus: a cross-sectional, community-based study.

Limited published data exist on the association between parity (number of deliveries) and diabetes mellitus (DM). This study was conducted to evaluate the association between parity and type 2 DM (T2DM) among Sudanese women. A multistage sampling survey was conducted in four villages in the River Nile State, Sudan, between July and September 2022. The World Health Organization's three-level stepwise questionnaire was adopted to collect women's sociodemographic characteristics (age, sex, height, weight, marital status, parity, education level, occupation, detailed obstetric history, and family history of T2DM). Multivariate analyses were performed. A total of 397 women were recruited. Their median (interquartile range) age was 45.0 (33.0‒55.7) years. A total of 154 women (38.8%) were nulliparous, whereas 93 (23.4%), 70 (17.6%), and 80 (20.2%) had para 1‒3, 4 or 5, and more than 5, respectively. A total of 112 (28.2%) women had T2DM. In multivariate analysis, older age (adjusted odds ratio, AOR, 1.04, 95%, confidence interval, CI, 1.02‒1.06), high parity (AOR, 1.1, 95% C, 1.01‒1.20), and a family history of DM (AOR, 3.26, 95% CI, 1.98‒5.38) were associated with T2DM. Compared with the nulliparity, para 1‒3 (AOR, 2.33; 95% CI, 1.17‒4.61), para 4 or 5 (AOR, 2.12; 95% CI, 1.04‒4.30), and para > 5 (AOR, 2.16; 95% CI, 1.09‒4.27) were at higher risk of T2DM. In women aged < 50 years, high parity (AOR, 1.22; 95% CI, 1.06‒1.44) was associated with T2DM. Compared with the nulliparous women, para 4 or 5 (AOR, 3.47; 95% CI, 1.16‒10.34) and para > 5 (AOR, 4.63; 95% CI, 1.54‒13.87) were associated with T2DM, whereas para 1‒3 was not associated with T2DM. In the women aged ≥ 50 years, parity and parity groups were not associated with T2DM. There is a high prevalence of T2DM among Sudanese women. Parity and high parity are significant predictors of T2DM among these women in this part of Sudan.

Perspective on the health effects of unsaturated fatty acids and commonly consumed plant oils high in unsaturated fat.

Epidemiological and clinical trial evidence indicates that n-6 polyunsaturated fatty acid (PUFA) intake is cardioprotective. Nevertheless, claims that n-6 PUFA intake promotes inflammation and oxidative stress prevail. This narrative review aims to provide health professionals with an up-to-date evidence overview to provide the requisite background to address patient/client concerns about oils containing predominantly unsaturated fatty acids (UFA), including MUFA and PUFA. Edible plant oils, commonly termed vegetable oils, are derived from vegetables, nuts, seeds, fruits and cereal grains. Substantial variation exists in the fatty acid composition of these oils; however, all are high in UFA, while being relatively low in saturated fatty acids (SFA), except for tropical oils. Epidemiological evidence indicates that higher PUFA intake is associated with lower risk of incident CVD and type 2 diabetes mellitus (T2DM). Additionally, replacement of SFA with PUFA is associated with reduced risk of CVD and T2DM. Clinical trials show higher intake of UFA from plant sources improves major CVD risk factors, including reducing levels of atherogenic lipids and lipoproteins. Importantly, clinical trials show that increased n-6 PUFA (linoleic acid) intake does not increase markers of inflammation or oxidative stress. Evidence-based guidelines from authoritative health and scientific organisations recommend intake of non-tropical vegetable oils, which contain MUFA and n-6 PUFA, as part of healthful dietary patterns. Specifically, vegetable oils rich in UFA should be consumed instead of rich sources of SFA, including butter, tallow, lard, palm and coconut oils.

Childhood socioeconomic differences in type 2 diabetes: longitudinal results of The Maastricht study

Abstract Background Type 2 diabetes mellitus (T2DM) is a common chronic disease that disproportionally affects disadvantaged groups. People with a low socioeconomic position (SEP) have an increased risk of developing T2DM. Knowing the potential influence of early life on T2DM risk later in life, this study aims to examine longitudinal associations between childhood SEP and type 2 diabetes, independent of adult SEP. Methods Longitudinal data was used from 6,727 participants of The Maastricht Study without T2DM at baseline (participants with prediabetes were included in the study sample). T2DM status was determined by a standardized oral glucose test. Sample mean (SD) age was 58.7 (8.7) years and 55.2% was female. Childhood SEP was determined by the highest level of completed education for father and mother and a measurement for childhood income inadequacy. Adult SEP was determined by the highest completed level of education, equivalent household income and occupational position. Incident T2DM was self-reported yearly. Associations were studied annually over a 12-year period (median (IQR) 8.2 (4.9) years) with Cox regression analyses. Results A total of 247 participants (3.7%) without T2DM at baseline reported incident T2DM. Incident T2DM was more common in people with low childhood SEP versus high childhood SEP (4.5% vs. 2.7%, p = 0.008) and for people with low adult SEP versus high adult SEP (5.2% vs. 2.1%, p &amp;lt; 0.001). The impact of parental education on incident T2DM is mitigated by adult SEP. Childhood income inadequacy did predict T2DM independently of adult SEP, with a HR of 1.22 (1.01, 1.45). Conclusions Socioeconomic inequalities in childhood and adulthood are both predictive for incident T2DM. Experiencing income inadequacy in childhood increases the risk of developing T2DM in later life, independent of adulthood SEP. More attention is needed for deprivation in childhood and its impact on T2DM. Key messages • People who have experienced income inadequacy as a child have a higher risk of developing T2DM in later life, independent of their adult SEP. • More attention and research is needed for the impact of childhood poverty on developing T2DM in later life.

The Presence of Heavy Metals in Drinking Water and Its Possible Impact on the Development of Type 1 Diabetes in Children

This study aimed to determine the relationship between the concentration of heavy metals in drinking water and the number of type 1 diabetes mellitus (T1DM) cases in two regions of Poland. The number of births in 2015-16 in Pomeranian Voivodeship was 50,461, while the number of new T1DM cases was 219. In Lublin Voivodeship, the number of births in the same period reached 39,381, and the number of new T1DM cases was 221. The incidence of T1DM, calculated per 100 live births, amounted to 0.43 and 0.56 in Pomeranian and Lublin. The statistical analysis of collected data proved that the number of new T1DM cases in Pomeranian Voivodeship is correlated to the concentrations of selenium (Se; p &lt; 0.0001), lead (Pb; p &lt; 0.00001), cadmium (Cd; p &lt; 0.00001), zinc (Zn; p &lt; 0.00001) and arsenic (As; p = 0.00001). In the case of Lublin Voivodeship, the number of new T1DM cases was correlated to the concentrations of Se (p = 0.0000001), Pb (p &lt; 0.000001), Cd (p = 0.0000001) and Zn (p &lt; 0.00001) in drinking water. No correlation was found between the number of new T1DM cases and arsenic concentration in the drinking water samples from Lublin Voivodeship. The results indicated that environmental exposure to specific heavy metals may contribute to the risk of T1DM, underscoring the need for stringent environmental controls and public health policies to mitigate these risks.

The prevention and improvement effects of vitamin D on type 2 diabetes mellitus: evidence from an umbrella review on Meta-analyses of cohort studies and randomized controlled trials.

To clarify whether Vitamin D prevent the occurrence of type 2 diabetes mellitus (T2DM) and improve glucose control in T2DM patients, we conducted this umbrella review, taking into account the inconsistent results of existing Meta-analyses. We aim to reveal the causal relationship between Vitamin D and T2DM through summarizing Meta-analyses of observational studies, and clarify the improvement on glucose control in T2DM patients through summarizing Meta-analyses of RCT studies between Vitamin D supplementation and T2DM patients, especially in T2DM patients with Vitamin D deficiency. We collected the Meta-analyses of observational studies and RCTs in PubMed, Scopus, Embase, Web of Science, and Cochrane. 16 Meta-analyses (6 effect sizes for cohort studies and 10 effect sizes for RCTs) were included in the umbrella Meta-analyses. Random-effects model was carried out to calculate the pooled point estimates and their respective 95% confidence intervals (CI). The results revealed that lower 25(OH)D levels increased the risk of T2DM (Pooled ESRR = 1.34; 95%CI: 1.16, 1.53), Vitamin D supplementation ameliorated FBG (ES = -0.56; 95%CI: -1.00, -0.11), HbA1c (ES = -0.11; 95%CI: -0.20, -0.02), insulin (ES = -0.38; 95%CI: -0.59, -0.18) and HOMA-IR (ES = -0.37; 95%CI: -0.57, -0.16) in T2DM patients, especially in those with Vitamin D deficiency (FBG = -0.98; HbA1c = -0.27; HOMA-IR = -0.52). The present umbrella Meta-analyses demonstrates the potential benefits of higher serum Vitamin D levels and Vitamin D supplementation in reducing the development and symptoms of T2DM.

GC–MS analysis, molecular docking, and pharmacokinetic studies on Dalbergia sissoo barks extracts for compounds with anti-diabetic potential

Diabetes is a metabolic condition defined by abnormal blood sugar levels. Targeting starch-hydrolyzing enzymes and Dipeptidyl Peptidase 4 (DPP-4) expressed on the surface of numerous cells is one of the key strategies to lower the risk of Type-2 diabetes mellitus (T2DM). Dalbergia sissoo Roxb. bark (DSB) extracts have been reported to have anti-diabetic properties. This study intended to scientifically validate use of alcoholic and hydro-alcoholic extracts of DSB for T2DM by conducting preliminary phytochemical investigations, characterising potential phytochemicals using Fourier transform infrared (FT-IR) spectroscopy and Gas chromatography-mass spectrometry (GC–MS) analysis followed by comprehensive in-silico analysis. A qualitative phytochemical evaluation indicated the presence of alkaloids, phenolics, glycosides, conjugated acids and flavonoids. Ethanolic extracts showed highest total phenolic content (TPC) (127.072 ± 14.08031 μg GAE/g dry extract) and total flavonoid content (106.911 ± 5.84516 μg QE /g dry extract). Further FT-IR spectroscopy also revealed typical band values associated with phenol, alcohol, alkene, alkane and conjugated acid functional groups. The GC–MS analysis identified 139 compounds, 18 of which had anti-diabetic potential. In-silico ADMET analysis of potential compounds revealed 15 compounds that followed Lipinski’s rule and demonstrated drug-like properties, as well as good oral bioavailability. Molecular docking was utilised to analyse their potential to interact with three targets: α-amylase, α-glucosidase, and DPP-4, which are crucial in managing diabetes-related problems. Molecular Docking analysis and membrane permeability test utilising the PerMM platform revealed that compounds in the extracts, such as Soyasapogenol B and Corydine, had better interactions and permeability across the plasma membrane than standard drugs in use. Molecular dynamics simulations also showed that selected compounds remained stable upon interaction with α-amylase. Overall, using the in-silico approaches it was predicted that DSB extracts contain potential phytochemicals with diverse anti-diabetic properties. It further needs to be investigated for possible development as formulation or drug of choice for treating T2DM.

Association between visceral adiposity index, lipid accumulation product and type 2 diabetes mellitus in US adults with hypertension: a cross-sectional analysis of NHANES from 2005 to 2018

BackgroundThe presence of hypertension significantly increases the risk of diabetes, particularly type 2 diabetes. Recently, Visceral Adiposity Index (VAI) has been introduced as a straightforward and robust alternative indicator for early detection of metabolic syndrome, cardiovascular disease, and T2DM. Visceral adiposity, more dangerous than subcutaneous fat, is associated with metabolic syndrome and cardiovascular diseases. The VAI and Lipid Accumulation Product (LAP) are indices that quantify visceral fat and lipid overaccumulation, respectively. This study aims to explore the association between VAI, LAP, and type 2 diabetes mellitus (T2DM) in US adults with hypertension using NHANES data from 2005 to 2018.MethodsWe analyzed data from 5,620 participants with hypertension in The National Health and Nutrition Examination Survey (NHANES). VAI and LAP were calculated using established formulas. The VAI is calculated based on a combination of waist circumference, body mass index (BMI), triglycerides, and high-density lipoprotein (HDL) cholesterol levels. Logistic regression models were applied to evaluate the association between these indices and T2DM, adjusting for potential confounders. Subgroup analyses by age and gender were also conducted to assess variations in risk.ResultsIn all, 5,620 participants were enrolled in our analysis, with 2,754 (49%) being female, and a mean (standard deviation, SD) age of 57 (15) years. The mean (SD) cumulative average VAI and LAP among all participants was 241 (2.71) and 75 (67), respectively. Totally, higher VAI and LAP indices were significantly associated with an increased risk of T2DM in individuals with hypertension. For VAI, the odds ratios (OR) for T2DM were higher in older adults (≥ 60 years) [95% confidence interval (CI): 1.37, 1.22–1.53, per 1 SD increase] and females [95% confidence interval (CI): 1.39, 1.27–1.52, per 1 SD increase], indicating age and gender differences in risk. Non-linear relationships were observed, suggesting thresholds beyond which the risk of T2DM escalates dramatically.ConclusionsBoth VAI and LAP are reliable markers for assessing T2DM risk in individuals with hypertension. Incorporating these indices into clinical practice could enhance the identification of high-risk individuals and facilitate early intervention strategies. Future longitudinal studies are needed to confirm these associations and explore targeted interventions.

High-fat diet promotes type 2 diabetes mellitus by disrupting gut microbial rhythms and short-chain fatty acid synthesis.

Diabetes ranks among the top 10 causes of death globally, with over 90% of individuals diagnosed with diabetes having type 2 diabetes mellitus (T2DM). It is acknowledged that a high-fat diet (HFD) poses a serious risk for T2DM. The imbalance of intestinal flora, mediated by HFD, can potentially exacerbate the onset and progression of T2DM. However, the impact of HFD on pathological indicators and the intestinal microbiome in the development of T2DM has not been systematically investigated. Therefore, a HFD mouse model and a T2DM mouse model were established, respectively, in this study. The role of HFD as a driving factor in the development of T2DM was assessed using various measures, including basic pathological indicators of T2DM, lipid metabolism, liver oxidative stress, intestinal permeability, levels of inflammatory factors, gut microbiota, and short-chain fatty acids (SCFAs). The findings indicated that HFD could influence the aforementioned measures to align with T2DM changes, but the contribution of HFD varied across different pathological metrics of T2DM. The impact of HFD on low-density lipoprotein cholesterol, glutathione peroxidase, malondialdehyde, and tumor necrosis factor-α did not show a statistically significant difference from those observed in T2DM during its development. In addition, regarding gut microbes, HFD primarily influenced the alterations in bacteria capable of synthesizing SCFAs. The notable decrease in SCFA content in both serum and cecal matter further underscored the effect of HFD on SCFA-synthesising bacteria in mice. Hence, this research provided a systematic assessment of HFD's propelling role in T2DM's progression. It was inferred that gut microbes, particularly those capable of synthesizing SCFAs, could serve as potential targets for the future prevention and treatment of T2DM instigated by HFD.

Role of vitamin D in prevention of type 2 diabetes mellitus: A systematic review and meta‑analysis.

The escalating prevalence of diabetes mellitus, projected to affect over 700 million by 2045, underscores the urgent need for effective management and prevention strategies, with type 2 diabetes mellitus (T2DM) constituting over 90% of these cases globally. The present meta-analysis aims to rigorously evaluate the potential of vitamin D supplementation in mitigating the onset of T2DM, amidst the backdrop of its biological plausibility yet inconclusive evidence regarding its efficacy in reducing new incidences of the disease. A comprehensive literature search up to December 2023 in MEDLINE, EMBASE and the Cochrane Library, employing a strategy focused on diabetes and vitamin D, identified randomized controlled trials (RCTs) that explore the impact of vitamin D supplementation on T2DM onset in adults with impaired glucose regulation, incorporating quality assessment via the Cochrane ROB2 tool and utilizing meta-analysis with RevMan Web to evaluate effect magnitude and heterogeneity. In a meta-analysis of 11 RCTs with 5,221 prediabetic patients, vitamin D supplementation was associated with a 10% reduction in the progression to T2DM [RR, 0.90; 95% CI, (0.81-0.99)] and a significant increase in regression to normoglycemia [RR, 1.24; 95% CI, (1.08-1.43)], with no significant heterogeneity or publication bias observed. This meta-analysis of 11 RCTs shows that vitamin D supplementation in prediabetic patients lowers the risk of T2DM and promotes regression to normoglycemia, with no significant differences in subgroup analyses or interaction with baseline vitamin D levels, ethnicity, or body mass index (BMI). Despite indications from some trials that baseline vitamin D status may influence outcomes, the present comprehensive analysis found benefits of vitamin D across diverse populations, including non-obese individuals, without conclusive evidence linking supplementation to changes in BMI or age-specific advantages.

7515 Plasma proteomic signatures for type 2 diabetes mellitus and related traits in the UK Biobank

Abstract Disclosure: T. Gupte: None. Z. Azizi: None. K. Nzenkue: None. P. Kho: None. M. Chen: None. J. Zhou: None. R. Guarischi-Sousa: None. D.J. Panyard: None. F. Abbasi: None. K. Watson: None. S. Clarke: None. P.S. Tsao: None. T.L. Assimes: None. Background: The plasma proteome holds promise as a future diagnostic and prognostic tool that can accurately reflect complex human traits and disease processes. We assessed the ability of plasma proteins to associate with two primary risk factors of type 2 diabetes mellitus (T2DM) and to predict incident T2DM. Methods: Clinical, genetic, and high-throughput proteomic data from three subcohorts of 5586, 5584, and 36339 individuals in the UK Biobank were analyzed for association with DXA-measured truncal fat, maximum VO2, and incident T2DM, respectively. Exclusion criteria included prevalent T2DM, history of T1DM, or elevated A1c (&amp;gt;48 mmol/mol) values. We used LASSO to assess relative ability of 13 clinical variables including the Q-Diabetes (Q-D) score, 36 polygenic risk scores (PRSs), and 2923 proteins to associate with each trait by comparing variances explained (R2) and AUC statistics between data types. Stability selection with randomized LASSO identified the most robustly associated proteins for each trait. The benefit of proteomic signatures (PSs) over the Q-D score was evaluated through the derivation of Δ AUC values. Separate case-control groups were developed to evaluate T2DM prediction in the adiposity and fitness cohorts. Results: Across all three subcohorts, the mean age was 56.6 years, 54.9% were female, and 5.4% developed T2DM over a median follow-up of 7.7 years. In the adiposity cohort, a protein-only LASSO model explained 73.2% of the variance in truncal fat and GLIPR1, CLMP, LEP, FABP4, and FAM3C were among the top proteins selected. In the fitness cohort, a protein-only LASSO model explained 61.9% of the variance in maximum VO2 and LEP, CD99, AGRN, ELN, and CA14 were among the top proteins selected. LASSO-derived PSs increased the R2 of truncal fat and maximum VO2 over clinical and genetic factors by 13% and 1%, respectively, with the former also improving risk prediction of T2DM over Q-D [Δ AUC: 0.026 (95% CI -0.007, 0.060)]. In the T2DM cohort, a protein-only LASSO model returned an AUC of 0.856 (95% CI 0.840, 0.871) and PLXNB2, PODXL, PLA2G7, FGFR2, and NFASC were among the top proteins selected. We observed a similar improvement in T2DM prediction over Q-D [Δ AUC: 0.015 (95% CI 0.009, 0.023)] when using a PS derived strictly from the T2DM outcome and augmented with non-overlapping proteins associated with fat and fitness. A few proteins (ranging between 15-33 for each trait) identified by stability selection algorithms offered most of the improvement in risk prediction. Conclusion: Plasma PS modestly improves the prediction of T2DM over that possible with clinical and genetic factors. Further studies are warranted to better elucidate the clinical utility of these signatures in predicting T2DM risk over the standard practice of using the Q-D score. Presentation: 6/2/2024

Relationships between APOE, Type 2 Diabetes, and Cardiovascular Disease in Postmenopausal Women.

The Apolipoprotein E (APOE) ε4 allele, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD) are well-established risk factors for dementia. Relationships between APOE and incidence of T2DM and CVD are not fully understood but may shed light on the mechanisms underlying dementia pathogenesis. Postmenopausal women (N=6,795) from the Women's Health Initiative hormone therapy clinical trial with APOE genotyping and no prior diagnosis of T2DM or CVD were included. We examined associations of APOE status (APOE2+ [ε2/ε2, ε2/ε3], APOE3 [ε3/ε3], and APOE4+ [ε4/ε4, ε3/ε4] carriers) with incidence of T2DM, coronary heart disease (CHD), stroke, and total CVD events using Cox regression. CVD outcomes were examined in baseline non-statin users and adjusted for statin initiation over follow-up to account for possible confounding by statins. Among all participants (mean age 66.7±6.5 years, 100% non-Hispanic white), 451 (6.6%) were using statins at baseline. Over the follow-up (mean 14.9 and 16.0 years for T2DM and CVD, respectively), 1,564 participants developed T2DM and 1,578 developed CVD. T2DM incidence did not differ significantly by APOE status (ps≥0.09). Among non-statin users, APOE4+ had higher incidence of total CVD (hazard ratio [95% confidence interval]=1.18 [1.02-1.38], p=0.03) compared to APOE3 carriers, but risks for CHD (1.09 [0.87-1.36], p=0.47) and stroke (1.14 [0.91-1.44], p=0.27) were not significantly elevated when examined individually. CVD outcomes did not differ between APOE2+ and APOE3 carriers (ps≥0.11). T2DM risk did not differ by APOE status among postmenopausal women, but APOE4+ carriers not using statins had an increased risk of total CVD events.