Prevalence Of T2D Research Articles

The Influence of Remnant Cholesterol on Cardiovascular Risk and Mortality in Patients with Non-Functional Adrenal Incidentalomas and Mild Autonomous Cortisol Secretion: A Retrospective Cohort Study.

Background: Increased cardiovascular risk has been described in individuals with adrenal incidentalomas. The aim of the present study is to assess the effect of remnant cholesterol (RC) on the cardiovascular risk and mortality of patients with adrenal incidentalomas. Methods: A retrospective cohort study was conducted with patients with adrenal incidentalomas between 2001 and 2024. One hundred thirty-seven patients (mean age of 61.2 ± 11.5 years; 56.6% women) with non-functioning adrenal incidentalomas and with mild autonomous cortisol secretion (MACS) (cortisol post-dexamethasone suppression test ≥1.8 µg/mL) were included. The patients were divided into two groups using 30 mg/dL as the cut-off for RC. Logistic regression models were used to study the impact of RC on major adverse cardiovascular events and mortality (MACEs). Results: Patients with RC ≥ 30 mg/dL exhibited a higher prevalence of type 2 diabetes mellitus (T2D) (p < 0.001), lower HDL-C (p < 0.001) and LDL-C (p = 0.025) levels, a higher frequency of treatment with statins (p = 0.032), and a higher rate of non-fatal major cardiovascular events (p = 0.038) and MACEs (p = 0.038). Patients with MACS showed no differences in RC or complications during the follow-up. The relative risk of high RC was 2.65 (1.04-6.77) for cardiovascular events and 2.27 (1.05-4.92) for MACEs, with p < 0.05 in both cases. The only variables independently affecting MACEs were age ([odds ratio] OR = 1.13 [p = 0.004]), female sex (OR = 0.20; p = 0.016), LDL-C (OR = 1.02; p = 0.029), and RC (OR = 1.06; p = 0.014). T2D and HDL-C were not independently associated with MACEs. Conclusions: RC ≥30 mg/dL in patients with adrenal incidentalomas was associated with a higher prevalence of T2D, lower HDL-C levels, and a higher risk of MACEs. MACS was not associated with RC or MACEs during the follow-up.

Global genomic profile of hippocampal endothelial cells by single-nuclei RNA sequencing in female diabetic mice is associated with cognitive dysfunction.

Type II diabetes mellitus (T2D) is a chronic metabolic disease and a risk factor for cardiovascular disease and cerebrovascular dysfunction including vascular dementia. Sex differences in the prevalence of T2D, dementia, and global genomic changes in the brain have been observed; however, most studies have been performed in males. Therefore, our aim was to evaluate the consequence of T2D on cognitive function and decipher the underlying molecular transcriptomic mechanisms of endothelial cells in an important brain memory center, the hippocampus, using a female murine diabetes model. We assessed cognitive function, metabolic parameters, and then performed hippocampal single-nuclei RNA sequencing (snRNA seq) in adult female db/db and control wild-type (WT) mice. db/db mice exhibited characteristic T2D metabolism with hyperglycemia, hyperinsulinemia, and hyperlipidemia when compared with WT mice. Female db/db mice presented cognitive decline compared with wild-type mice, as determined by open field and Morris water maze tests. snRNAseq showed that T2D induced significant changes in the global transcriptomic profile of hippocampal endothelial cells by modulating the expression of not only protein-coding genes but also long noncoding RNAs. These genes regulate cell-cell junctions, cell chemotaxis, actin cytoskeleton organization, and cell adhesion, suggesting that diabetes increases endothelial cell permeability. Observed genomic changes also correlated with the genetics of persons with clinical Alzheimer's disease and vascular dementia. In conclusion, T2D, by transcriptional and posttranscriptional regulation, regulates endothelial cell dysfunction predictive of increased vascular permeability, and negatively impacts cognitive function. Our work has implications for sex-specific molecular therapeutic targets for dementia in females.NEW & NOTEWORTHY Female db/db mice presented cognitive decline as determined by open field and Morris water maze tests. snRNAseq showed that T2D induced changes in the global transcriptomic profile of hippocampal endothelial cells by modulating the expression of not only protein-coding genes but also long noncoding RNAs. These genes regulate cell-cell junctions, cell chemotaxis, or cell adhesion, suggesting increased endothelial permeability. Genomic changes correlated with the genetics of persons with clinical Alzheimer's disease and vascular dementia.

Measuring Diabetic Medication Adherence and Factors That Lead to Non-adherence Among Patients in Erbil.

Introduction T2D is a chronic and progressive disorder characterized by persistent hyperglycemia resulting from inadequate insulin secretion or utilization. The global prevalence of T2D is increasing rapidly, posing a significant health burden in many regions. In the Kurdistan region of Iraq, T2D presents a significant health burden, exacerbated by socioeconomic changes, dietary shifts, and rising obesity rates. Poor adherence to antidiabetic medications is a major factor contributing to poor glycemic control, accelerating disease progression, and increasing complications. This study aims to assess medication adherence rates among adult T2D patients in Erbil using the Kurdish version of the Morisky Medication Adherence Scale-8 (MMAS-8) and identify factors associated with non-adherence. Methods We conducted a cross-sectional study at public and private clinics in Erbil City, Kurdistan, Iraq, between May 1 and September 30, 2023. A convenience sample of 300 adult Kurdish T2D patients, aged ≥ 25 years and on antidiabetic medications for three months or more, was recruited. Data were collected using a structured questionnaire comprising sociodemographic characteristics, clinical and anthropometric measures, and medication adherence assessed by the Kurdish version of the MMAS-8. Statistical analysis included analysis of variance, Kruskal-Wallis, chi-square, and logistic regression models to identify factors associated with medication adherence. Results Of the 300 participants, 81 (27%) demonstrated high adherence, 98 (32.6%) moderate adherence, and 121 (40.3%) low adherence based on the MMAS-8. Low adherence was significantly associated with lower education (56/121, 46.3% vs. 13/81, 16.0%, p < 0.001), unemployment (73/121, 60.3% vs. 29/81, 35.8%, p = 0.008), rural residence (41/121, 33.9% vs. 10/81, 12.3%, p < 0.001), and lower income (62/121, 51.2% vs. 12/81, 14.8%, p < 0.001). High adherence was linked to better diabetes knowledge, home glucose monitoring, and exercise. High adherence was also associated with better glycemic control, with 76/81 (93.8%) of highly adherent patients achieving glycated hemoglobin (HbA1c) <7%, compared to 15/121 (12.4%) in the low adherence group (p < 0.001). Multivariate analysis identified HbA1c, dyslipidemia, and home blood glucose monitoring as independent factors associated with high adherence. Conclusions This study highlights the substantial impact of socioeconomic, behavioral, and clinical factors on medication adherence among T2D patients in Erbil. Low adherence is associated with lower education, income, and awareness of diabetes management, while high adherence is linked to improved glycemic control and reduced complications. Targeted interventions addressing these factors are essential to enhance adherence and optimize T2D management in this population.

Global trends in clinical trials and interventions for the metabolic syndrome: A comprehensive analysis of the WHO International Clinical Trials platform

Metabolic syndrome has emerged as a significant global public health concern, necessitating comprehensive examination alongside cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2D). This study provides a comprehensive analysis of clinical trials, drawing upon data sourced from the International Clinical Trials Registry Platform (ICTRP), until April 2023. Information pertaining to trial attributes and intervention features was gathered and subsequently summarized. Among the 2379 studies found on ICTRP from 18 clinical registries, ClinicalTrials.gov was the most popular with 55 % of the studies, based on data emerging from the United States. Most trials were for treatment (44 %) and prevention (17 %), with fewer focused on basic science, and diagnostic purposes. Diet and exercise were the most prominent, with 710 and 247 studies, respectively. Metformin and statins emerge as leading pharmacological therapies, reflecting the prevalence of CVD and T2D in the context of metabolic syndrome. However, there is growing recognition of other promising interventions, such as Glucagon-Like Peptide-1 agonists and Dipeptidyl Peptidase IV inhibitors, which offer potential in slowing the progression of metabolic syndrome-related conditions. Notably, clinical trials primarily assessed diagnostic markers like lipid profiles, insulin, and blood pressure, rather than body mass and body mass index. These parameters are crucial for evaluating the effectiveness and safety of interventions for metabolic syndrome due to its multi-condition nature. Most studies aimed to address general symptom relief, while highlighting a need for additional well-designed treatment trials with rigorous methodologies in accordance with the World Health Organization's guidance for consistent evaluation and treatment.

The relationship between schizophrenia or schizoaffective disorder and type1 diabetes mellitus: ascoping review of observational studies.

Both schizophrenia and type1 diabetes mellitus (T1D) are known as immune-related disorders. We systematically reviewed observational studies to explore the relationship between schizophrenia or schizoaffective disorder and T1D. Apreliminary search of articles was completed using the following databases: Airiti Library, CINAHL Complete (via EBSCOhost), OVID MEDLINE, Embase, and PubMed. Two researchers independently assessed each study's quality based on Joanna Briggs Institute (JBI). Anarrative review summarized the potential relationship between the two diseases. Eleven studies were included in the final analysis. Six observational studies investigated the risk of schizophrenia and schizoaffective disorder in patients with T1D. Two studies showed negative correlations, one showed no correlation, and three showed positive correlations. On the other hand, five studies reported the prevalence of T1D in patients with schizophrenia. Two of them showed positive associations, and three others showed no association. Although the majority of the included studies suggested apositive association between the two medical conditions, these studies were still too heterogeneous to draw consistent results. We found conflicting results regarding the bidirectional relationship between schizophrenia or schizoaffective disorder and T1D. These may stem from differences in study design, sampling methods, or definition of diagnoses, which are essential aspects to consider in future research.

The future burden of type 2 diabetes in Belgium: a microsimulation model

ObjectiveTo forecast the annual burden of type 2 diabetes and related socio-demographic disparities in Belgium until 2030.MethodsThis study utilized a discrete-event transition microsimulation model. A synthetic population was created using 2018 national register data of the Belgian population aged 0–80 years, along with the national representative prevalence of diabetes risk factors obtained from the latest (2018) Belgian Health Interview and Examination Surveys using Multiple Imputation by Chained Equations (MICE) as inputs to the Simulation of Synthetic Complex Data (simPop) model. Mortality information was obtained from the Belgian vital statistics and used to calculate annual death probabilities. From 2018 to 2030, synthetic individuals transitioned annually from health to death, with or without developing type 2 diabetes, as predicted by the Finnish Diabetes Risk Score, and risk factors were updated via strata-specific transition probabilities.ResultsA total of 6722 [95% UI 3421, 11,583] new cases of type 2 diabetes per 100,000 inhabitants are expected between 2018 and 2030 in Belgium, representing a 32.8% and 19.3% increase in T2D prevalence rate and DALYs rate, respectively. While T2D burden remained highest for lower-education subgroups across all three Belgian regions, the highest increases in incidence and prevalence rates by 2030 are observed for women in general, and particularly among Flemish women reporting higher-education levels with a 114.5% and 44.6% increase in prevalence and DALYs rates, respectively. Existing age- and education-related inequalities will remain apparent in 2030 across all three regions.ConclusionsThe projected increase in the burden of T2D in Belgium highlights the urgent need for primary and secondary preventive strategies. While emphasis should be placed on the lower-education groups, it is also crucial to reinforce strategies for people of higher socioeconomic status as the burden of T2D is expected to increase significantly in this population segment.

Impact of the trans-ancestry polygenic risk score on type 2 diabetes risk, onset age and progression among population in Taiwan.

Type 2 diabetes (T2D) prevalence in adults at a younger age has increased but the disease status may go unnoticed. This study aimed to determine whether the onset age and subsequent diabetic complications can be attributed to the polygenic architecture of T2D in the Taiwan Han population. A total of 9,627 cases with T2D and 85,606 controls from the Taiwan Biobank were enrolled. Three diabetic polygenic risk scores (PRSs), PRS_EAS and PRS_EUR, and a trans-ancestry PRS (PRS_META), calculated using summary statistic from East Asian and European populations. The onset age was identified by linking to the National Taiwan Insurance Research Database, and the incidence of different diabetic complications during follow-up was recorded. PRS_META (7.4%) explained a higher variation for T2D status. And the higher percentile of PRS is also correlated with higher percentage of T2D family history and prediabetes status. More, the PRS was negatively associated with onset age (β = -0.91 yr), and this was more evident among males (β = -1.11 vs. -0.76 for males and females, respectively). The hazard ratio of diabetic retinopathy (DR) and diabetic foot were significantly associated with PRS_EAS and PRS_META, respectively. However, the PRS was not associated with other diabetic complications, including diabetic nephropathy, cardiovascular disease, and hypertension. Our findings indicated that diabetic PRS which combined susceptibility variants from cross-population could be used as a tool for early screening of T2D, especially for high-risk populations, such as individuals with high genetic risk, and may be associated with the risk of complications in subjects with T2D. NEW & NOTEWORTHY Our findings indicated that diabetic polygenic risk score (PRS) which combined susceptibility variants from Asian and European population affect the onset age of type 2 diabetes (T2D) and could be used as a tool for early screening of T2D, especially for individuals with high genetic risk, and may be associated with the risk of diabetic complications among people in Taiwan.

Assessing the readiness to transition to adult care, perceived medication barriers, and glycemic control among teens with type 1 diabetes

AimThis study assessed the readiness to transition (RT) from pediatric to adult care, perceived medication barriers (PMB), and glycemic control in teens with type one diabetes (T1D). BackgroundDuring the transition from pediatric to adult care, teens with T1D are at risk of long-term complications related to impaired adherence. With the increasing prevalence of T1D in Saudi Arabia, research is required to identify the challenges facing teens with T1D during their transition. MethodsThis was a cross-sectional study with a convenient sample of 83 adolescents (12–17 years old) diagnosed with T1D for ≥6 months, their parents, and their pediatric endocrinologists from the pediatric endocrinology clinic in a tertiary hospital in Riyadh. The RT Questionnaire was used to measure RT, and the Medication Barriers Scale was used to measure PMB. Glycemic control was measured using hemoglobin A1c (HbA1c). ResultsAbout 96 % of teens had HbA1c > 7 %. Male teens had higher HbA1c than female teens. Teens and their parents reported high PMB and low RT. PMB (teens), disease duration, family history of diabetes mellitus, and comorbidity were significant predictors of RT (parents). PMB (teens), teens' age, and having a family history of diabetes mellitus were significant predictors of RT (providers). RT (parents) and RT (providers) were the only significant predictors of HbA1c, with RT (providers) being the strongest predictors of HbA1c. ConclusionsHealth policy reform is required to develop national RT programs to prepare teens with T1D to take full responsibility for managing their medical conditions while ensuring adherence.

Type 2 diabetes severity in the workforce: An occupational sector analysis using German claims data.

Individuals of working age spend a significant amount of time at the workplace making it an important context for disease prevention and management. The temporal development and prevalence of T2D have been shown to differ in the working population based on gender, age group and occupational sector regardless of socioeconomic status. Given potential differences in risk factors associated with different work environments, this study aims to define vulnerable occupational groups by examining T2D severity and its trends in working men and women with T2D of two age groups and among nine occupational sectors. The study is based on claims data of the statutory health insurance provider AOKN. The study population consisted of all insured working individuals with T2D. T2D severity was measured using the adapted diabetes complications severity index-complication count (DCSI-CC). Mean DCSI-CC scores were calculated over four time periods between 2012 and 2019 for men and women of the age groups 18-45 and 46+ years and among nine occupational sectors. Trends of DCSI-CC were investigated using ordinal logistic regression analyses to examine the effect of time-period on the odds of having higher DCSI scores. Overall, there was a significant rise in T2D severity over time in working men and women of the older age group. Moreover, the study displayed occupational sector differences in T2D severity and its trends. Over all, working men of all sectors had higher DCSI-CC scores compared to working women. Individuals working in the sector "Transport, logistics, protection and security" and "Construction, architecture, measuring and building technology" had higher T2D severity, while those working in the "Health sector, social work, teaching & education" had relatively lower T2D severity. There was a gender-specific significant increase over time in T2D severity in the above-mentioned occupational sectors. The study displayed gender, age group and occupational sector differences in T2D severity and its trends. Working individuals could thus benefit from personalized prevention interventions that consider occupational contexts. As a next step, examining T2D trends and severity in specific occupations within the vulnerable occupational sectors is needed.

Altered Gut Microbiota as a Potential Risk Factor for Coronary Artery Disease in Diabetes: A Two-Sample Bi-Directional Mendelian Randomization Study.

The current body of research points to a notable correlation between an imbalance in gut microbiota and the development of type 2 diabetes mellitus (T2D) as well as its consequential ailment, coronary artery disease (CAD). The complexities underlying the association, especially in the context of diabetic coronary artery disease (DCAD), are not yet fully understood, and the causal links require further clarification. In this study, a bidirectional Mendelian randomization (MR) methodology was utilized to explore the causal relationships between gut microbiota, T2D, and CAD. By analyzing data from the DIAGRAM, GERA, UKB, FHS, and mibioGen cohorts and examining GWAS databases, we sought to uncover genetic variants linked to T2D, CAD, and variations in gut microbiota and metabolites, aiming to shed light on the potential mechanisms connecting gut microbiota with DCAD. Our investigation uncovered a marked causal link between the presence of Oxalobacter formigenes and an increased incidence of both T2D and CAD. Specifically, a ten-unit genetic predisposition towards T2D was found to be associated with a 6.1% higher probability of an increase in the Oxalobacteraceae family's presence (β = 0.061, 95% CI = 0.002-0.119). In a parallel finding, an augmented presence of Oxalobacter was related to an 8.2% heightened genetic likelihood of CAD (β = 0.082, 95% CI = 0.026-0.137). This evidence indicates a critical pathway by which T2D can potentially raise the risk of CAD via alterations in gut microbiota. Additionally, our analyses reveal a connection between CAD risk and Methanobacteria, thus providing fresh perspectives on the roles of TMAO and carnitine in the etiology of CAD. The data also suggest a direct causal relationship between increased levels of certain metabolites - proline, lysophosphatidylcholine, asparagine, and salicylurate - and the prevalence of both T2D and CAD. Sensitivity assessments reinforce the notion that changes in Oxalobacter formigenes could pose a risk for DCAD. There is also evidence to suggest that DCAD may, in turn, affect the gut microbiota's makeup. Notably, a surge in serum TMAO levels in individuals with CAD, coinciding with a reduced presence of methanogens, has been identified as a potentially significant factor for future examination.

Dopamine D2 receptor antagonist counteracts hyperglycemia and insulin resistance in diet-induced obese male mice.

Obesity leads to insulin resistance (IR) and type 2 diabetes. In humans, low levels of the hormone prolactin (PRL) correlate with IR, adipose tissue (AT) dysfunction, and increased prevalence of T2D. In obese rats, PRL treatment promotes insulin sensitivity and reduces visceral AT adipocyte hypertrophy. Here, we tested whether elevating PRL levels with the prokinetic and antipsychotic drug sulpiride, an antagonist of dopamine D2 receptors, improves metabolism in high fat diet (HFD)-induced obese male mice. Sulpiride treatment (30 days) reduced hyperglycemia, IR, and the serum and pancreatic levels of triglycerides in obese mice, reduced visceral and subcutaneous AT adipocyte hypertrophy, normalized markers of visceral AT function (PRL receptor, Glut4, insulin receptor and Hif-1α), and increased glycogen stores in skeletal muscle. However, the effects of sulpiride reducing hyperglycemia were also observed in obese prolactin receptor null mice. We conclude that sulpiride reduces obesity-induced hyperglycemia by mechanisms that are independent of prolactin/prolactin receptor activity. These findings support the therapeutic potential of sulpiride against metabolic dysfunction in obesity.

CONSANGUINITY AS A SIGNIFICANT RISK FACTOR FOR DIABETES MELLITUS: A SYSTEMATIC REVIEW

Objectives:This systematic review aims to study the recent updates regarding the association between consanguinity and DM. Methods:PubMed, SCOPUS, Web of Science, and Science Direct were systematically searched for relevant literature. Rayyan QRCI was employed throughout this comprehensive process. Results&amp; interpretation: Our results included ten studies with a total of 8878 patients, and 4565 (51.4%) were males. Eight studies included patients with T2D, and two included T1D. The prevalence of consanguinity ranged from 21.9% to 95% in T2D and 70.8% in T1D.PreoperThe development of T2D was significantly influenced by consanguinity, consanguineous marriages, and maternal diabetes, particularly in developing Arab countries where the prevalence of T2D in families is very high. Significant risk variables for T2D in MetS patients were consanguineous marriages, maternal aunts, maternal grandpas, and the presence of MetS in the parents family. A family history of autoimmune disease in children or paternal consanguinity is not strongly associated with the complexity of T1D.

CONSANGUINITY AS A SIGNIFICANT RISK FACTOR FOR DIABETES MELLITUS: A SYSTEMATIC REVIEW

Objectives:This systematic review aims to study the recent updates regarding the association between consanguinity and DM. Methods:PubMed, SCOPUS, Web of Science, and Science Direct were systematically searched for relevant literature. Rayyan QRCI was employed throughout this comprehensive process. Results&amp; interpretation: Our results included ten studies with a total of 8878 patients, and 4565 (51.4%) were males. Eight studies included patients with T2D, and two included T1D. The prevalence of consanguinity ranged from 21.9% to 95% in T2D and 70.8% in T1D.PreoperThe development of T2D was significantly influenced by consanguinity, consanguineous marriages, and maternal diabetes, particularly in developing Arab countries where the prevalence of T2D in families is very high. Significant risk variables for T2D in MetS patients were consanguineous marriages, maternal aunts, maternal grandpas, and the presence of MetS in the parents family. A family history of autoimmune disease in children or paternal consanguinity is not strongly associated with the complexity of T1D.

191-LB: The Impact of Urbanization on the People of the Upper Amazon

Although it has gotten little attention, T2D has become a public health issue in the Peruvian Amazon, particularly among urban dwellers. The growing rate of T2D in the global south has been attributed to greater access to industrial foods and sedentary lifestyles ensuant of rapid urbanization. In Amazonia, people migrate from rural communities to urban hubs searching for socioeconomic opportunities. As a result, prevalence of T2D and obesity has rapidly increased in these cities. Our study compared the diabetes status of people living in Yurimaguas (YU) with those living in traditional rural villages in the Balsapuerto District (BD), Peru, to understand health differences between rural and urban Amazonians. Methods Participants were recruited in YU (M/F = 114/52) and 11 rural villages in BD (F/M = 92/77). We collected blood pressure, glucose, insulin, glycosylated hemoglobin (A1c), lipids panels, and body measurements. T2D status was determined using ADA guidelines for A1c and glucose. Results Mean age of participants was younger in BD (44.4 yrs) compared to YU (50.3 yrs; t335 = 3.52, p &amp;lt; 0.01). After adjusting for age, we found participants in YU had greater A1c (F2, 328 = 49.14, p &amp;lt; 0.01), BMI (F2, 328 = 28.79, p &amp;lt; 0.01), glucose (F2, 328 = 8.85, p &amp;lt; 0.01), insulin (F2, 328 = 7.11, p &amp;lt; 0.01), triglycerides (F2, 328 = 3.84, p &amp;lt; 0.01), and systolic pressure (F2, 328 = 37.45, p &amp;lt; 0.01) compared to participants living in BD. The proportion of individuals with diabetes and prediabetes was greater in YU (37%, 34% respectively) compared to BD (4%, 12% respectively; χ2 = 119.9, df =2, p &amp;lt; 0.01). The percentage of individuals with BMIs &amp;gt; 25 in YU was 68% (n = 112) and 29% (n = 49) in BD respectively (χ2 = 51.8, df =1, p &amp;lt; 0.01). Discussion Results suggest Peruvians living in YU generally had poor health profiles, higher incidence of diabetes, and higher BMIs compared to their rural counterparts 40km away. Given the stark differences between these communities, efforts should be made to understand the nutritional and lifestyle factors leading to this health decline. Disclosure C. Gerhold: None. D. C. Robbins: None. M. Garcia-touza: None. B. C. Dean: None. Funding Kansas University Diabetes Institute

1288-P: Predictive Modeling of Type 2 Diabetes and Complications Using Machine Learning

Background: Given the prevalence of T2D worldwide, early detection and prevention of both T2D and its complications are of utmost importance. We propose comprehensive person-centered machine learning (ML) risk prediction models for T2D and complications. Methods: From the UK biobank (UKBB), we identified a prevalent T2D group at baseline (9,136 cases and 108,615 controls), an incident T2D group over 10 years of follow-up (29,845 cases and 354,818 controls), and an incident diabetic kidney disease (DKD) group (4435 cases and 33083 controls). We included 3 types of risk factors: clinical (biomarkers and diseases with known diabetes risk like CVD), genetic in the form of polygenic risk scores (PRS) for the pathogenesis of T2D and other clinical risks, and lifestyle. For each group, we trained a model using decision-tree-based ensemble ML algorithm. We then used SHAP values to determine feature importance and chose the top 10 predictors to build a final model. Results: The T2D prevalence model included 74 features and had an AUC of 0.97, and area under the precision-recall curve (PR AUC) of 0.83. The final model with the top features (HbA1c, T2D PRS, primary HTN, LDL, major dietary changes in the last 5 years, age, plasma glucose, waist circumference, and total cholesterol) had an AUC of 0.98, and PR AUC of 0.88. The T2D incidence model included the same 74 features and had an AUC of 0.92, and PR AUC of 0.57. The final model with the top features had an AUC of 0.93, and PR AUC of 0.65. The DKD risk prediction model comprised 85 features, and it had an AUC of 0.81, and PR AUC of 0.37. The final model with the top features (Cystatin C, primary HTN, eGFR, age, HbA1c, T2D PRS, urea, BMI, BMI PRS, NAFLD PRS) had an AUC of 0.80, and PR AUC of 0.39. Conclusions: This study is an ongoing work; our interim results show the capability of ML to identify relevant risk factors and that comprehensive ML models could help clinicians decide on more precise and individualized T2D screening and treatment approaches to prevent T2D and complications. Disclosure A.Khattab: None. S.Chen: None. H.J.Sadaei: None. A.Torkamani: None.

The impact of childhood traumatization on diabetes mellitus type 2 (T2D) risk in World War II refugees and their offspring.

T2D is a chronic disease that is influenced by different factors. The extent to which degree adverse childhood events (ACEs) can modify the potential to development of T2D is still not explored and therefore represents one of the central questions of the CELLO (childhood escape - late life outcome, DRKS00012419) study. In addition, transgenerational effects were considered in the analyses. The study analyzed the association of self-reported traumatic experiences and T2D disease of refugees from East Prussia, who were displaced from their former homeland at the end of the World War II. In addition, an independent sample consisting of participants of first-generation offspring of refugees was analyzed. Of the 242 refugees, all aged between 73 and 93, 17.36% reported T2D disease, while among the offspring (n = 272), aged between 47 and 73, it was 5.5%, meaning reduced T2D prevalence for both generations compared to the German population of comparable age. In the refugee generation, emotional neglect showed a negative association with development of T2D in later life. In women, separation from close caregivers in childhood showed a negative association with later T2D. In contrast, experiencing emotional abuse in childhood showed a positive association with later T2D. The offspring generation showed no associations of ACEs and reported T2D diagnoses in later life. Our results demonstrate that individual trauma in childhood is responded to with different mechanisms that can lead to both increased and decreased reported T2D diagnoses in adulthood and thus should by no means be considered in a generalized manner.

Personalized diet intervention in Thai ageing populations

Personalized diet intervention in Thai ageing populations Professor Apichart Vanavichit a Rice Genomic Breeding Expert at the Rice Science Center looks at diet intervention and therapy for the ageing population of Thailand to prevent disease. Thailand has rapidly become an ageing society, and the average age of the Thais will be 30 years older compared to 1975. As the elderly population increases, it is anticipated that there will be more incidences of non-communicable diseases (NCDs) such as obesity (OB), diabetes (T2D), and cardiovascular disease (CVD). Notably, the prevalence of T2D has increased rapidly from 6.5% in 2015 to 10.7% in 2030 (estimated), with the most significant increase will be found among the elderly population (72%). In developing countries, NCD has become the most immense burden among the poor elderly whose life depends on their children. There are strong links between consuming high glycemic index foods, a sedentary lifestyle, and NCDs. So, developing lower glycemic index meals and changing lifestyles with diet intervention programmes are sensible solutions to slow down the prevalence of future NCDs.

Association between serum calcium level and type 2 diabetes: An NHANES analysis and Mendelian randomization study.

This study investigated the association between serum calcium levels and the prevalence of T2D using a cross-sectional study and Mendelian randomization analysis. Cross-sectional data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Serum calcium levels were divided into three groups (low, medium and high groups) according to the tertiles. Logistic regression was used to estimate the association between serum calcium levels and T2D prevalence. Instrumental variables for serum calcium levels were obtained from the UK Biobank and a two-sample MR analysis was performed to examine the causal relationship between genetically predicted serum calcium levels and the risk of T2D. A total of 39,645 participants were available for cross-sectional analysis. After adjusting for covariates, participants in the high serum calcium group had significantly higher odds of T2D (OR=1.18, 95% CI=1.07, 1.30, p=0.001) than those in the moderate group. Restricted cubic spline plots showed a J-shaped curve relationship between serum calcium level and prevalence of T2D. Consistently, Mendelian randomization analysis showed that higher genetically predicted serum calcium levels were causally associated with a higher risk of T2D (OR=1.16, 95% CI: 1.01, 1.33, p = 0.031). The results of this study suggest that higher serum calcium levels are causally associated with a higher risk of T2D. Further studies are needed to clarify whether intervening in high serum calcium could reduce the risk of T2D.

Dopamine receptor agonists mechanism of actions on glucose lowering and their connections with prolactin actions.

Robust experiment evidence suggests that prolactin can enhance beta-cell proliferation and increase insulin secretion and sensitivity. Apart from acting as an endocrine hormone, it also function as an adipokine and act on adipocytes to modulate adipogenesis, lipid metabolism and inflammation. Several cross-sectional epidemiologic studies consistently showed that circulating prolactin levels positive correlated with increased insulin sensitivity, lower glucose and lipid levels, and lower prevalence of T2D and metabolic syndrome. Bromocriptine, a dopamine receptor agonist used to treat prolactinoma, is approved by Food and Drug Administration for treatment in type 2 diabetes mellitus since 2009. Prolactin lowering suppress insulin secretion and decrease insulin sensitivity, therefore dopamine receptor agonists which act at the pituitary to lower serum prolactin levels are expected to impair glucose tolerance. Making it more complicating, studies exploring the glucose-lowering mechanism of bromocriptine and cabergoline have resulted in contradictory results; while some demonstrated actions independently on prolactin status, others showed glucose lowering partly explained by prolactin level. Previous studies showed that a moderate increase in central intraventricular prolactin levels stimulates hypothalamic dopamine with a decreased serum prolactin level and improved glucose metabolism. Additionally, sharp wave-ripples from the hippocampus modulates peripheral glucose level within 10 minutes, providing evidence for a mechanistic link between hypothalamus and blood glucose control. Central insulin in the mesolimbic system have been shown to suppress dopamine levels thus comprising a feedback control loop. Central dopamine and prolactin levels plays a key role in the glucose homeostasis control, and their dysregulation could lead to the pathognomonic central insulin resistance depicted in the "ominous octet". This review aims to provide an in-depth discussion on the glucose-lowering mechanism of dopamine receptor agonists and on the diverse prolactin and dopamine actions on metabolism targets.

Role of leisure sedentary behavior on type 2 diabetes and glycemic homeostasis: a Mendelian randomization analysis.

Utilize Mendelian randomization (MR) to examine the impact of leisure sedentary behavior (LSB) on the prevalence of type 2 diabetes mellitus (T2D) and glycemic homeostasis impairment, as well as to identify potential mediating pathways involved in these associations. We chose genetic variants linked to LSB from a large genome-wide association study (GWAS) to use as instrumental variables (IVs). Then, we used a two-sample MR study to investigate the link between LSB and T2D and glycemic homeostasis. Multivariate MR (MVMR) and mediation analysis were also used to look at possible mediating paths. MR analysis showed a genetical link between leisure TV watching and T2D (OR 1.64, 95% CI 1.39-1.93, P< 0.001) and impaired Glycemic Homeostasis, while leisure computer use seemed to protect against T2D prevalence (OR 0.65, 95% CI 0.50-0.84, P< 0.001). It was found that leisure TV watching increases the risk of T2D through higher BMI (mediation effect 0.23, 95% CI 0.11-0.35, P< 0.001), higher triglycerides (mediation effect 0.07, 95% CI 0.04-0.11, P< 0.001), and less education (mediation effect 0.16, 95% CI 0.08-0.24, P< 0.001). Sensitivity and heterogeneity analyses further substantiated the robustness of these findings. Reverse MR analysis did not yield significant results. This study shows LSB is linked to a higher rate of T2D and impaired glycemic homeostasis through obesity, lipid metabolism disorders, and reduced educational attainment.