Greater Risk Of Diabetes Research Articles

The Association of Adiposity and RAAS With Incident Diabetes in African Americans: The Jackson Heart Study.

The renin-angiotensin-aldosterone system (RAAS) and adiposity measures are independently associated with the development of diabetes in African American adults. However, studies have not examined the combined interaction between RAAS and adiposity measures in relation to diabetes risk in African American adults. We examined the longitudinal association of combined RAAS and adiposity measures with incident diabetes among African American adults in the Jackson Heart Study. African American adults were assessed at baseline (2000-2004) and over 12 years of follow-up. RAAS, anthropometric (waist circumference [WC], body mass index), and adipokine (adiponectin, leptin, leptin to adiponectin ratio [LAR]) measures were collected at baseline. Aldosterone, WC, and LAR were chosen as the best predictor variables. The final model, adjusting for age, sex, education, occupation, systolic blood pressure, smoking, physical activity and RAAS-altering medications, incorporated these variables and their interactions (WC*aldosterone + LAR*aldosterone) to explore their impact on incident diabetes. Among 3219 participants without diabetes at baseline, there were 554 incident cases over a median follow-up period of 7.5 years. Aldosterone, WC, and LAR were positively associated with incident diabetes (all P < .05). A significant interaction was found between WC and aldosterone, with a greater association among individuals with lower WC. This interaction was significant in participants with prediabetes but not in those with normoglycemia. No significant interaction was found between log-LAR and aldosterone with risk of incident diabetes. Higher aldosterone in participants is associated with greater risk of diabetes, particularly among individuals with prediabetes and lower WC.

Systemic Immune-Inflammation Index in Relation to Diabetes Markers in Saudi Adults: A Retrospective Study.

Background and objectives: Low-grade inflammation is associated with metabolic disturbances like diabetes. The systemic immune-inflammation index (SII) has been proposed as a predictive tool to identify individuals at a greater risk of diabetes. This study aims to examine the association between SII and diabetes markers. Method and materials: We used retrospective data from a large cohort of adults (n = 3895) aged ≥18 in Saudi Arabia. The SII was calculated, and the markers of diabetes such as fasting blood glucose (FBG), insulin, and hemoglobin A1c (HbA1c) were included. Results: Across the quartiles of SII, FBG, insulin, and HbA1c were significantly higher in adults with higher compared to lower SII (p < 0.0001, p = 0.04, p < 0.0001, respectively). A two SD higher FBG was significantly associated with an SII difference of 47.7 (95% CI: (15.5, 91.9)). In subgroup analysis, this relationship prevailed in normal-weight participants and among those with normoglycemia and prediabetes but was attenuated in participants with diabetes. The association also prevailed in separate analyses for males and females but was stronger among females. Linear regression models showed no significant association between insulin, HbA1c, and SII. Conclusions: SII was associated with the markers of diabetes. The utility of SII for predicting diabetes can be confirmed with prospective cohort studies.

GLP-1 Agonism for Kidney Transplant Recipients: A Narrative Review of Current Evidence and Future Directions Across the Research Spectrum.

Diabetes is the most common cause of kidney disease in individuals that receive a kidney transplant, and those without pre-existing diabetes are at greater risk of developing diabetes following kidney transplant. A class of diabetes treatment medications called glucagon-like peptide-1 receptor agonists (GLP-1RA) has seen recent widespread use for people with diabetes or obesity, with efficacy for improved glycemic control, weight loss, and reduced risk of cardiovascular events. Given these benefits, and indications for use that often co-occur in kidney transplant recipients, use of GLP-1RAs warrants consideration in this population. Therefore, we sought to review the current literature to better understand the mechanisms of action, clinical application, and person-centred considerations of GLP-1RAs in kidney transplant recipients. Original articles were identified between December 2023 and July 2024 from electronic databases including the Ovid MEDLINE database, PubMed, and Google Scholar using terms "kidney transplant," "GLP-1," "glucagon-like peptide-1 receptor agonist," and "diabetes." A comprehensive review of the literature was conducted to explore the relationship between GLP-1RAs and kidney transplant recipients. We reviewed the current state of evidence across the research disciplines of basic or fundamental science, clinical and health services research, and person-centred equity science, and highlighted important knowledge gaps that offer opportunities for future research. Numerous clinical studies have demonstrated the benefit of GLP-1RAs in people with and without diabetic kidney disease, including decreased risk of cardiovascular events. However, there is a paucity of high-quality randomized controlled trials and observational studies analyzing use of GLP-1RAs in kidney transplant recipients. Evidence of benefit in this population is therefore limited to small studies or inferred from research conducted in nontransplant populations. Growing evidence from preclinical and clinical studies may elucidate renoprotective mechanisms of GLP-1RAs and remove barriers to application of these drugs in the transplant recipient population. Individuals who are female, non-white, have lower socioeconomic status, and live in rural communities are at greater risk of diabetes and have lower uptake of GLP-1RAs. There is a need for clinical trials across diverse kidney transplant populations to estimate the efficacy of GLP-1RAs on important health outcomes. The search strategy for this narrative review may not have been sensitive to identify all relevant articles. Our search was limited to English language articles.

Type 2 diabetes metabolomics score and risk of progression to type 2 diabetes among women with a history of gestational diabetes mellitus.

Several metabolites are individually related to incident type 2 diabetes (T2D) risk. We prospectively evaluated a novel T2D-metabolite pattern with a risk of progression to T2D among high-risk women with a history of gestational diabetes mellitus (GDM). The longitudinal Nurses' Health Study II cohort enroled 116,429 women in 1989 and collected blood samples from 1996 to 1999. We profiled plasma metabolites in 175 incident T2D cases and 175 age-matched controls, all with a history of GDM before the blood draw. We derived a metabolomics score from 21 metabolites previously associated with incident T2D in the published literature by scoring according to the participants' quintile (1-5 points) of each metabolite. We modelled the T2D metabolomics score categorically in quartiles and continuously per 1 standard deviation (SD) with the risk of incident T2D using conditional logistic regression models adjusting for body mass index at the blood draw, and other established T2D risk factors. The percentage of women progressing to T2D ranged from 10% in the bottom T2D metabolomics score quartile to 78% in the highest score quartile. Adjusting for established T2D risk factors, women in the highest quartile had more than a 20-fold greater diabetes risk than women in the lowest quartile (odds ratios [OR]=23.1 [95% CI=8.6, 62.1]; p for trend<0.001). The continuous T2D metabolomics score was strongly and positively associated with incident T2D (adjusted OR=2.7 per SD [95% CI=1.9, 3.7], p<0.0001). A pattern of plasma metabolites among high-risk women is associated with a markedly elevated risk of progression to T2D later in life.

The Prevalence of Metabolically Unhealthy Normal Weight and Its Influence on the Risk of Diabetes.

Diabetes is a major health problem and metabolically unhealthy is an important risk factor. To conduct the first nationally representative study on epidemiological data of metabolically unhealthy normal weight (MUNW) focused only on nondiabetic subjects and determine the predictive effect on diabetes in China. A longitudinal study was conducted using data from the Rich Healthcare Group in China. Metabolic status was determined by the revised National Cholesterol Education Program Adult Treatment Panel III criteria, and individuals with 2 or more criteria were categorized as MUNW and diagnosed with metabolic syndrome (MetS) if they met 3 or more. Of a total of 63 830 nondiabetic normal-weight individuals, 8935 (14.0%) were classified as MUNW and 1916 (3.00%) were diagnosed with MetS. After adjusting for potential confounders, individuals with MUNW had a greater diabetes risk (4.234, 95% CI 3.089-5.803) than those without MUNW during an average of 3.10 years of follow-up. Also, the multivariable-adjusted hazard ratios for developing diabetes were 3.069 (95% CI 1.790-5.263), 7.990 (95% CI 4.668-13.677), and 11.950 (95% CI 6.618-21.579) for participants with 1, 2, and 3 or more components, respectively, compared with those without any components. Further analyses suggested that the number of MetS components present is associated with the risk of diabetes, especially in metabolically unhealthy normal-weight young male adults. Multivariable-adjusted hazard ratios (95% CI) for incident diabetes among individuals with 1, 2, and at least 3 components were 4.45 (1.45-13.72), 9.82 (3.05-31.64), and 15.13 (3.70-61.84) for participants aged ≤44 years, and 3.55 (1.81-6.97), 8.52 (4.34-16.73), and 13.69 (6.51-28.77) for male participants, respectively. The prevalence of MUNW is 14% in Chinese normal-weight nondiabetic individuals, and active intervention is necessary for this category of people. The presence of MUNW significantly increases the risk of diabetes, and the risk of diabetes is associated with the number of MetS components present in the patient.

Quantifying the Negative Impact of Fast-food Consumption on Liver Steatosis Among United States Adults With Diabetes and Obesity

Fast-food consumption is highly prevalent in the United States (U.S.) and associated with greater risk of diabetes and cardiovascular disease.1 However, little is known about the impact of fast-food consumption on the risk of nonalcoholic fatty liver disease (NAFLD), which affects over 30% of the U.S. population, or whether the effect of fast food on steatosis is different among persons with metabolic risk factors, including obesity and diabetes. Dietary intake has been hypothesized to be one of the most influential modifiable factors for NAFLD, yet there are major gaps in evidence linking diet with steatosis, particularly among high-risk groups, limiting public health efforts around dietary prevention and risk mitigation strategies to reduce fatty liver.

Sex and gender-specific aspects in prediabetes and diabetes mellitus-clinical recommendations (Update 2023)

Metabolic diseases dramatically affect the life of men and women from infancy up to old age in different and manifold ways and are amajor challenge for the healthcare system. The treating physicians are confronted with the different needs of women and men in the clinical routine. Gender-specific differences affect pathophysiology, screening, diagnostic and treatment strategies of diseases as well as the development of complications and mortality rates. Impairments in glucose and lipid metabolism, regulation of energy balance and body fat distribution and therefore the associated cardiovascular diseases, are greatly influenced by steroidal and sex hormones. Furthermore, education, income and psychosocial factors play an important role in the development of obesity and diabetes differently in men and women. Males appear to be at greater risk of diabetes at ayounger age and at alower body mass index (BMI) compared to women but women feature adramatic increase in the risk of diabetes-associated cardiovascular diseases after the menopause. The estimated future years of life lost owing to diabetes is somewhat higher in women than men, with ahigher increase in vascular complications in women but ahigher increase of cancer deaths in men. In women prediabetes or diabetes are more distinctly associated with ahigher number of vascular risk factors, such as inflammatory parameters, unfavourable changes in coagulation and higher blood pressure. Women with prediabetes and diabetes have amuch higher relative risk for vascular diseases. Women are more often morbidly obese and less physically active but may have an even greater benefit in health and life expectation from increased physical activity than men. In weight loss studies men often showed ahigher weight loss than women; however, diabetes prevention is similarly effective in men and women with prediabetes with arisk reduction of nearly 40%. Nevertheless, along-term reduction in all cause and cardiovascular mortality was so far only observed in women. Men predominantly feature increased fasting blood glucose levels, women often show impaired glucose tolerance. Ahistory of gestational diabetes or polycystic ovary syndrome (PCOS) as well as increased androgen levels and decreased estrogen levels in women and the presence of erectile dysfunction or decreased testosterone levels in men are important sex-specific risk factors for the development of diabetes. Many studies showed that women with diabetes reach their target values for HbA1c, blood pressure and low-density lipoprotein (LDL)-cholesterol less often than their male counterparts, although the reasons are unclear. Furthermore, sex differences in the effects, pharmacokinetics and side effects of pharmacological treatment should be taken more into consideration.

Persistence of β-Cell Responsiveness for Over Two Years in Autoantibody-Positive Children With Marked Metabolic Impairment at Screening.

We studied longitudinal differences between progressors and nonprogressors to type 1 diabetes with similar and substantial baseline risk. Changes in 2-h oral glucose tolerance test indices were used to examine variability in diabetes progression in the Diabetes Prevention Trial-Type 1 (DPT-1) study (n = 246) and Type 1 Diabetes TrialNet Pathway to Prevention study (TNPTP) (n = 503) among autoantibody (Ab)+ children (aged <18.0 years) with similar baseline metabolic impairment (DPT-1 Risk Score [DPTRS] of 6.5-7.5), as well as in TNPTP Ab- children (n = 94). Longitudinal analyses revealed annualized area under the curve (AUC) of C-peptide increases in nonprogressors versus decreases in progressors (P ≤ 0.026 for DPT-1 and TNPTP). Vector indices for AUC glucose and AUC C-peptide changes (on a two-dimensional grid) also differed significantly (P < 0.001). Despite marked baseline metabolic impairment of nonprogressors, changes in AUC C-peptide, AUC glucose, AUC C-peptide-to-AUC glucose ratio (AUC ratio), and Index60 did not differ from Ab- relatives during follow-up. Divergence between nonprogressors and progressors occurred by 6 months from baseline in both cohorts (AUC glucose, P ≤ 0.007; AUC ratio, P ≤ 0.034; Index60, P < 0.001; vector indices of change, P < 0.001). Differences in 6-month change were positively associated with greater diabetes risk (respectively, P < 0.001, P ≤ 0.019, P < 0.001, and P < 0.001) in DPT-1 and TNPTP, except AUC ratio, which was inversely associated with risk (P < 0.001). Novel findings show that even with similarly abnormal baseline risk, progressors had appreciably more metabolic impairment than nonprogressors within 6 months and that the measures showing impairment were predictive of type 1 diabetes. Longitudinal metabolic patterns did not differ between nonprogressors and Ab- relatives, suggesting persistent β-cell responsiveness in nonprogressors.

Life-course blood pressure trajectories and incident diabetes: A longitudinal cohort in a Chinese population.

Blood pressure levels are correlated with diabetes among middle-aged or older adults. However, longitudinal trajectories of blood pressure during young adulthood and their impact on diabetes have been insufficiently studied. The longitudinal cohort consisted of 4,625 adults who had blood pressure and body mass index (BMI) repeatedly measured five to nine times during 18-60 years of age. Distinct systolic blood pressure (SBP) trajectories were identified by a group-based trajectory model. Logistic regression analyses were used to investigate the association between trajectory patterns or quartiles of area under the curve values of SBP trajectories and incident diabetes, respectively. Four distinct trajectory groups were identified for SBP: normotensive-stable (n = 761, 16.5%), prehypertension-stable (n = 2,381, 51.5%), stage I hypertension-increasing (n = 1,231, 26.6%), and stage II hypertension-increasing (n = 251, 5.4%). Compared with subjects who remained at SBP <120 mmHg in the normotensive-stable group, individuals in the prehypertension-stable trajectory exhibited a normal SBP range (<140 mmHg), and they still had a significantly higher risk of diabetes (adjusted OR = 1.82, p = 0.029). Individuals had a greater risk of diabetes in the stage I hypertension-increasing group (adjusted OR = 2.31, p = 0.006) and the highest risk in the stage II hypertension-increasing group (adjusted OR = 3.91, p < 0.001) relative to the normotensive-stable group. Furthermore, compared with the first quartile, adjusted ORs (95% CIs) of the fourth quartile of SBP incremental and total AUC were 2.50 (1.61-3.97) and 1.82 (1.15-2.94), respectively. Long-term SBP trajectory is a significant predictor for incident diabetes, which is independent of baseline SBP and body weight, attaching importance to maintaining optimal blood pressure levels and controlling changing slopes of SBP for preventing diabetes.

S1240 Quantifying the Negative Impact of Fast-Food Consumption on Liver Steatosis Among U.S. Adults in the General Population

Introduction: Fast food (FF) consumption is highly prevalent in the US and is associated with high caloric intake and greater risk of diabetes. Little is known about the impact of FF consumption on NAFLD risk in healthy adults or whether the effect of FF on steatosis is different among persons with metabolic risk factors, including obesity and diabetes. We aimed to evaluate the quantitative impacts of FF consumption on steatosis risk in these populations. Methods: Adults (≥20 years) in the U.S. National Health and Nutrition Examination Survey 2017-2018 with valid transient elastography and FF data were included. Liver steatosis was measured continuously using the controlled attenuated parameter score (CAP; dB/m). FF intake was assessed using the two-day food frequency questionnaire and calculated as the percentage of daily calories from FF (either as an average of the two-day total or one day if only one day was available). We used multivariable linear regression to examine the association of FF consumption with steatosis. Results: 3,954 adults were included, of whom 2037 (52%) consumed any FF and 1,147 (29%) consumed >20% of daily calories from FF. Subjects consuming >20% of daily calories from FF (vs ≤20%) were more likely to be younger (42 vs 50 years), male (53% vs 47%), obese (50% vs 40%), consume sugar-sweetened beverages (SSBs; 43% vs 27%) and less likely to drink coffee (17% versus 24%). In the multivariable models, FF intake >20% of daily caloric intake was associated with a 4.3-point higher CAP (standard error [SE] 1.9) after controlling for age, gender, race/ethnicity, diabetes, body mass index, and consumption of SSBs or coffee. We identified interactions between FF intake >20% and metabolic comorbidities, including obesity (p< 0.001) and diabetes (p=0.054). Among diabetics, FF intake >20% (vs ≤20%) was associated with a 15.7-unit higher CAP (283[4.3] vs 268[4.2]), compared to only a 2.9-unit higher CAP among non-diabetics (249[1.4] vs 246[1.7]; Figure). Among obese persons, FF intake >20% was associated with a 11-unit higher CAP (296[3.1] vs 285[3.4]) compared to a 3-unit lower CAP compared to non-obese persons (232[1.4] vs 235[1.7]). Conclusion: Fast food consumption is associated with greater liver steatosis in the U.S. population, with striking elevations in risk among obese and diabetic persons. These findings should urge education around magnitude of risk among persons with obesity and diabetes and encourage policy efforts to improve access to healthier food options in the US.Figure 1.: Adjusted mean CAP score by the amount of fast-food consumption per daily caloric intake.

1174-P: A Posteriori Dietary Patterns and Insulin-Resistance Status and Diabetes Risk by Hispanic/Latino Heritage in HCHS/SOL

We examined links among dietary patterns (DPs) , insulin resistance (IR) , and diabetes risk by heritage (Cuban, Dominican, Mexican, Puerto Rican, and Central and South American) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) . HCHS/SOL is a population-based cohort of 16,415 Hispanics/Latinos aged 18-74 y living in 4 US cities. At both visits, questionnaires and clinical examinations were administered, including two 24-hr diet recalls conducted at baseline only (2008-11) . Among 7,774 participants with 2nd-visit data (2014-17) and without diabetes at baseline, we performed heritage-specific principal factor analyses and characterized overarching DPs based on high-loading foods shared by ≥ 2 heritage groups. We classified 6-yr IR status (improved, unchanged, worsened) using a SD-change in fasting insulin. We defined incident diabetes using self-report, self-reported diabetes medication, or labs (fasting glucose (≥126 mg/dL) , post-OGTT (≥200 mg/dL) , or HbA1C (≥6.5%)) . We identified 5 overarching DPs: Burger, Fries, &amp; Soft Drinks; White Rice, Beans, &amp; Red Meats; Fish &amp; Whole Grains; Cheese &amp; Sweets; and Stew &amp; Corn. Comparing highest to lowest quintiles, the Burger, Fries, &amp; Soft Drinks DP in Dominicans (log-odds: 2.35, 95% CI: 1.02, 3.68, P trend=0.037) and White Rice, Beans, &amp; Red Meats DP in Cubans (log-odds: 1.27, 95% CI: 0.49, 2.06, P trend =0.009) were associated with worsened (vs. unchanged) 6-year IR status. The Burger, Fries, &amp; Soft Drinks DP in Puerto Ricans (OR: 3.00, 95% CI:1.50, 5.99, P trend=0.003) and the White Rice, Beans, &amp; Red Meats DP in Central Americans (OR: 2.41, 95% CI: 1.05, 5.50, P trend=0.032) were associated with greater diabetes risk. In sum, dietary interventions for diabetes prevention should be tailored by Hispanic/Latino heritage. Disclosure L.E.Maldonado: None. L.Gallo: None. S.Albrecht: None. D.Sotres-alvarez: None. J.Mattei: None. M.L.Daviglus: None. G.A.Talavera: None. K.M.Perreira: None. L.Van horn: None. Y.Mossavar-rahmani: None. M.N.Lecroy: None. Funding The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233) , University of Miami (N01-HC65234) , Albert Einstein College of Medicine (N01-HC65235) , Northwestern University (N01-HC65236) , and San Diego State University (N01-HC65237) . The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Center on Minority Health and Health Disparities, the National Institute of Deafness and Other Communications Disorders, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the Office of Dietary Supplements. This research received support from the National Heart, Lung, and Blood Institute Global Cardiometabolic Disease Training Grant (1T32HL129969-01A1) , the National Institute of Diabetes and Digestive and Kidney Diseases (K01DK107791) ,and from the Population Research Infrastructure Program (R24 HD050924) awarded to the Carolina Population Center at The University of North Carolina at Chapel Hill by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

C-reactive Protein and Racial Differences in Type 2 Diabetes Incidence: The REGARDS Study.

Black adults experience more type 2 diabetes mellitus and higher inflammatory markers, including C-reactive protein (CRP), than White adults. Inflammatory markers are associated with risk of incident diabetes but the impact of inflammation on racial differences in incident diabetes is unknown. We assessed whether CRP mediated the Black-White incident diabetes disparity. The REasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30 239 US Black and White adults aged ≥45 years in 2003-2007 with a second visit approximately 10 years later. Among participants without baseline diabetes, adjusted sex- and race-stratified risk ratios for incident diabetes at the second visit by CRP level were calculated using modified Poisson regression. Inverse odds weighting estimated the percent mediation of the racial disparity by CRP. Of 11 073 participants without baseline diabetes (33% Black, 67% White), 1389 (12.5%) developed diabetes. Black participants had higher CRP at baseline and greater incident diabetes than White participants. Relative to CRP < 3 mg/L, CRP ≥ 3 mg/L was associated with greater risk of diabetes in all race-sex strata. Black participants had higher risk of diabetes at CRP < 3 mg/L, but not at CRP ≥ 3 mg/L. In women, CRP mediated 10.0% of the racial difference in incident diabetes. This mediation was not seen in men. Higher CRP is a risk factor for incident diabetes, but the excess burden of diabetes in Black adults was only seen in those with lower CRP, suggesting that inflammation is unlikely to be the main driver of this racial disparity.

Galectin-3 as a Novel Multifaceted and Not Only Cardiovascular Biomarker in Patients with Psoriasis with Regard to Systemic Treatment-Preliminary Data.

Simple SummaryGalectin-3 (gal-3) regulates many different biological processes and diseases, which are common accompanying diseases of psoriasis. Psoriasis is one of the most common skin diseases. There is little information about potential diagnostic role of gal-3 in psoriasis. Serum gal-3 concentrations were measured before and after twelve weeks of antipsoriatic treatment in patients with psoriasis and compared to 11 persons without psoriasis (control group). Serum gal-3 level in patients with psoriasis was significantly higher compared to the control group. In obese patients and long-lasting psoriasis positive relations of gal-3 and index of psoriasis severity were noted. In psoriatics with low gal-3 levels, it was noted that the higher the gal-3, the higher the BMI and glucose level. In patients with long history of psoriasis it was observed that the higher gal-3, the lower the lipids levels. The Gal-3 level might be a factor affecting the course of psoriasis and useful in prediction of cardiometabolic comorbidities, especially in patients with a long history of the disease or obesity. Patients with low serum gal-3 and a short history of psoriasis may have greater risk of diabetes. In obese patients with long-lasting psoriasis, gal-3 may have a beneficial influence against abnormal lipid profiles or perhaps further cardiovascular disorder development.Galectin-3 (gal-3) is a multifunctional regulator of various biological processes and diseases, which are common comorbidities in psoriasis. Data regarding potential diagnostic role of gal-3 in psoriasis are insufficient. Serum gal-3 levels were evaluated before and after twelve weeks of treatment with acitretin or methotrexate in 31 patients with plaque-type psoriasis and compared to 11 healthy control group. The mean serum galectin-3 level in patients with psoriasis was significantly higher compared to the control group (p < 0.01). In patients with obesity and long-lasting psoriasis (>20 years) positive relations of gal-3 and PASI were noted. In psoriatics with low gal-3 levels, positive correlations between the gal-3 and BMI, glucose level, and with the latter in short-lasting psoriasis (<20 years) were noted. In the long history of psoriasis, gal-3 was negatively correlated with lipids levels. The Gal-3 level might be a multifaceted modulator of the course of psoriasis and predictive factor of cardiometabolic comorbidities’ development, especially in patients with a long history of the disease or obesity. Patients with low serum gal-3 and short history of psoriasis are presumably at greater risk of diabetes. In patients with long-lasting psoriasis and concomitant obesity, gal-3 may exert a protective role against dyslipidemia or perhaps further CMD development.

Neurodegenerative brain changes are associated with area deprivation in the United Kingdom: findings from the Brains for Dementia Research study

Socioeconomic disadvantage is associated with greater risk of dementia. This has been theorised to reflect inequalities in cognitive reserve, healthcare access, lifestyle, and other health factors which may contribute to the clinical manifestation of dementia. We aimed to assess whether area deprivation in the United Kingdom was associated with greater risk or severity of the specific neurodegenerative diseases which lead to dementia in a multi-centre cohort with autopsy assessment. Participants underwent clinical assessment prior to brain tissue donation post-mortem. Each then underwent detailed, standardised neuropathological assessment. National area deprivation statistics were derived for each participant’s neighbourhood, for use as a predictor in binary and ordinal logistic models assessing the respective presence and severity of staging of key neuropathological changes, adjusting for theorised confounders. Individuals from among the 20% most deprived neighbourhoods in the United Kingdom had significantly higher neurofibrillary tangle and neuritic plaque staging, and increased risk of cerebral amyloid angiopathy. These findings were not explained by a greater risk of diabetes or hypertension, APOE genotype, alcohol misuse or tobacco smoking, sex, or age differences. A sensitivity analysis conditioning on baseline cognitive impairment did not meaningfully change the observed association. Socioeconomic disadvantage may contribute to dementia incidence through a greater severity of specific neuropathological changes (neurofibrillary tangles, neuritic plaques, and cerebral amyloid angiopathy), independent of other indirect influences. Mechanisms through which deprivation is associated with these require further exploration.

Relationship Between Insulin Secretion and Insulin Sensitivity and its Role in Development of Type 2 Diabetes Mellitus: Beyond the Disposition Index.

We assessed whether the relationship between insulin secretion and sensitivity predicted development of type 2 diabetes in American Indians participating in a longitudinal epidemiologic study. At baseline, when all subjects did not have diabetes, 1566 participants underwent oral tests and 420 had intravenous measures of glucose regulation with estimates of insulin secretion and sensitivity. Standardized major axis regression was used to study the relationship of secretion and sensitivity. Distances away from and along the regression line estimated compensatory insulin secretion and secretory demand, respectively. This relationship differed according to glucose tolerance and BMI categories. The distance away from the line is similar to the disposition index (DI) defined as the product of estimated secretion and sensitivity, but the regression line may differ from a line with constant DI (i.e., it is not necessarily hyperbolic). Subjects with the same DI but different levels of insulin secretion and sensitivity had different incidence rates of diabetes; lower sensitivity with higher secretory demand was associated with greater diabetes risk. Insulin secretion and insulin sensitivity, analyzed together, predict diabetes better than DI alone. Physiologically, this may reflect long-term risk associated with increased allostatic load resulting from the stimulation of insulin hypersecretion by increased glycemia.

A clinical diabetes risk prediction model for prediabetic women with prior gestational diabetes.

Without treatment, prediabetic women with a history of gestational diabetes mellitus (GDM) are at greater risk for developing type 2 diabetes compared with women without a history of GDM. Both intensive lifestyle intervention and metformin can reduce risk. To predict risk and treatment response, we developed a risk prediction model specifically for women with prior GDM. The Diabetes Prevention Program was a randomized controlled trial to evaluate the effectiveness of intensive lifestyle intervention, metformin (850mg twice daily), and placebo in preventing diabetes. Data from the Diabetes Prevention Program (DPP) was used to conduct a secondary analysis to evaluate 11 baseline clinical variables of 317 women with prediabetes and a self-reported history of GDM to develop a 3-year diabetes risk prediction model using Cox proportional hazards regression. Reduced models were explored and compared with the main model. Within three years, 82 (25.9%) women developed diabetes. In our parsimonious model using 4 of 11 clinical variables, higher fasting glucose and hemoglobin A1C were each associated with greater risk for diabetes (each hazard ratio approximately 1.4), and there was an interaction between treatment arm and BMI suggesting that metformin was more effective relative to no treatment for BMI ≥ 35kg/m2 than BMI < 30kg/m2. The model had fair discrimination (bias corrected C index = 0.68) and was not significantly different from our main model using 11 clinical variables. The estimated incidence of diabetes without treatment was 37.4%, compared to 20.0% with intensive lifestyle intervention or metformin treatment for women with a prior GDM. A clinical prediction model was developed for individualized decision making for prediabetes treatment in women with prior GDM.

249-OR: Type 2 Diabetes (T2D) Genetic Clusters for Association with Glycemic Responses to Intervention for Diabetes Prevention

Polygenic scores (PS) of T2D genetic variants based on pathophysiologic mechanisms underlying diabetes have been developed. We investigated whether T2D cluster PS influences response to interventions for diabetes prevention. We examined 2,647 DPP participants with impaired glucose tolerance and genetic data randomized to intensive lifestyle, metformin or placebo arms for diabetes prevention. We generated five PS clusters including β-cell related clusters (β-cell, proinsulin) and insulin resistance clusters (liver/lipid, obesity, lipodystrophy). We examined associations of PS with baseline and 1-year glycemic traits after intervention derived from oral glucose tolerance tests using general linear models, and with diabetes incidence over an average period of 3 years using Cox Regression Models. Models were adjusted for sex, age, and 10 principal components, respective baseline trait, and treatment group. At one-year follow-up, β-cell PS was associated with reduction in the insulinogenic index and corrected insulin response, in each treatment group and, statistically significant, in all combined (P&amp;lt;0.001), with no statistically significant interaction term between treatment groups, a finding consistent with a slightly increased diabetes incidence (HR 1.02 per weighted allele [CI 95% 1.00, 1.03]). The remaining PS were associated with baseline participant features, but not with diabetes incidence or change in glycemic parameters from baseline. We conclude that high genetic burden in β-cell cluster PS is associated with greater risk of diabetes and a decrease in insulin secretion, seen across all treatment groups. Despite interventions with intensive lifestyle and metformin, participants with high β-cell cluster genetic burden had an increased risk of diabetes and worsening in insulin secretion similar to placebo group. These data suggest that alternate therapies may be needed to prevent β-cell decline in this subset of prediabetes patients. Disclosure L. K. Billings: Advisory Panel; Self; Bayer Inc., Lilly Diabetes, Novo Nordisk, Sanofi. S. Raghavan: None. S. Srinivasan: None. J. Xu: None. J. C. Florez: Consultant; Self; Goldfinch Bio, Inc., Other Relationship; Self; Novo Nordisk. M. Udler: None. D. Research group: None. K. A. Jablonski: None. P. W. Franks: Advisory Panel; Self; Zoe Global Limited, Consultant; Self; Eli Lilly and Company, Novo Nordisk. R. B. Goldberg: None. M. Hivert: None. S. E. Kahn: Advisory Panel; Self; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk, Pfizer Inc. W. C. Knowler: None. C. Lee: None. J. Merino: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK048489)

Impact of HCV infection and ethnicity on incident type 2 diabetes: findings from a large population-based cohort in British Columbia

IntroductionIncreasing evidence indicates that chronic hepatitis C virus (HCV) infection is associated with higher risk of diabetes. Previous studies showed ethnic disparities in the disease burden of diabetes, with increased...

Abstract P023: Leukocyte Count, Adiposity And Incident Diabetes In A Biracial Cohort

Background: Diabetes is one the costliest diseases in the U.S, and excess inflammation associates with greater diabetes risk. Greater adiposity is associated with higher leukocyte count, but the interrelations of body size phenotype, leukocytes, and incident diabetes is unknown. Hypothesis: Body size phenotype and incident diabetes can be further understood using leukocyte count in Black and White people. Methods: The study included 8075 Black and White participants without diabetes at baseline (2003-2007) in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Body size phenotypes included metabolically healthy non-obese, metabolically healthy obese, metabolically unhealthy non-obese, and metabolically unhealthy obese. The interaction of leukocyte count with body size phenotype was assessed. As an exploratory analysis, data were further stratified by race. Results: The interaction of leukocyte count with body size phenotype was significant (p=0.02). In metabolically healthy individuals with or without obesity, the risk of diabetes increased across leukocyte quartiles. In healthy non-obese individuals, the risk of diabetes was 3 times higher in the top compared to the bottom quartile of leukocyte count and 4.5 times higher in unhealthy obese individuals. In contrast, there was no association in metabolically unhealthy participants with or without obesity. Considering race differences, in metabolically healthy non-obese persons, the association was 4 times higher for Black individuals and 2 times higher among White individuals. In the healthy obese group, these associations was larger in White than Black people. Conclusions: Higher leukocyte count is associated with the risk of diabetes in metabolically healthy individuals with or without obesity, but not among metabolically unhealthy individuals. Inflammation, as assessed by leukocyte count, does not identify added risk among those who are already classified as metabolically unhealthy.

Abstract P052: Less Appendicular Lean Mass Adjusted For Body Mass Index Is Associated With Higher Incident Diabetes In Middle-aged Adults In The CARDIA Study

Although less muscle mass is associated with greater diabetes prevalence in cross-sectional studies, prospective data in middle-aged Black and White adults are lacking. Middle age is a critical window as accelerated muscle loss is yet to occur, and preventing diabetes reduces lifelong morbidity and mortality. We hypothesized that lower appendicular lean mass adjusted for body mass index (ALM/BMI) is associated with higher incident diabetes in middle-aged Black and White adults in the Coronary Artery Risk Development in Young Adults (CARDIA) study. ALM/BMI was measured by dual x-ray energy absorptiometry (DXA) in 2005-06 among middle-aged US men (n=855) and women (n=1045) in CARDIA. Incident diabetes occurred if any of the following were met in 2010-11 or 2015-16 among persons without diabetes in 2005-06: fasting glucose ≥7 mmol/L (126 mg/dL), 2-hour glucose ≥11.1 mmol/L (200 mg/dL) on a 75-gram glucose tolerance test, HbA 1C ≥48 mmol/mol (6.5%), or use of glucose-lowering medications. We used logistic regression models with sex stratification given sex differences in ALM. In men, mean age was 45.0 ± 3.5 y, BMI 28.0 ± 4.3 kg/m 2 , and ALM/BMI 1.07 ± 0.14 m 2 . In women, mean age was 45.2 ± 3.6 years, BMI 28.4 ± 6.4 kg/m 2 , and ALM/BMI 0.73 ± 0.12 m 2 . Diabetes developed in 70 men (8.2%) and 72 women (6.9%). For each standard deviation increase in ALM/BMI (m 2 ), the risk of diabetes decreased by 22% in men and 29% in women (Table 1). After adjusting for age, race, smoking, education, physical activity, and waist circumference, the association of ALM/BMI with diabetes incidence was no longer significant. Associations were similar between race-ethnic groups. In conclusion, less relative skeletal muscle mass is associated with a greater risk of developing diabetes in middle-aged men and women over 10 years, which is largely explained by the relationship of ALM/BMI to other metabolic risk factors. Low skeletal muscle mass in middle age is a marker for greater diabetes risk and may be a target for preventative interventions.