Abstract 16055: Lipoprotein Subclasses, Size, and Statin-Associated Incident Diabetes: An Analysis From the JUPITER Trial

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sagar Dugani ◽  
Akintunde O Akinkuolie ◽  
Robert J Glynn ◽  
Paul M Ridker ◽  
Samia Mora
Keyword(s):  
Risk Factors ◽  
Cox Regression ◽  
Incident Diabetes ◽  
P Value ◽  
Random Allocation ◽  
Lipoprotein Subclass ◽  
Lipoprotein Subclasses ◽  
Ldl Particles ◽  
Ldl Size ◽  
Increased Risk

Statins reduce CVD events, LDL cholesterol (LDL-C) and triglycerides, with an increased risk of diabetes. The underlying predictors of statin-associated diabetes are unclear. We evaluated lipoprotein subclass and size changes in response to rosuvastatin to identify predictors of diabetes on statin therapy Among 11,918 non-diabetic participants in JUPITER (NCT00239681), lipoprotein subclasses and size were quantified by NMR spectroscopy (LipoScience, NC) prior to and 1 year after randomization to placebo or rosuvastatin (total 370 incident diabetes). Cox regression models were adjusted for diabetes risk factors Compared to baseline, rosuvastatin lowered LDL-C and particles by lowering cholesterol-enriched large LDL (58%) and IDL (46%), with less relative lowering of cholesterol-poor small LDL (22%), resulting in smaller LDL size (1.5%). Rosuvastatin lowered (15%-20%) triglycerides, VLDL triglycerides, and VLDL particles by lowering large (15%), medium (7%), and small (27%) particles, and increasing VLDL size (3%) (all p<0.0001). Among statin-allocated individuals, after adjusting for typical risk factors, incident diabetes was inversely associated with baseline levels of LDL-C, HDL-C, large LDL particles, and LDL size, and positively associated with baseline triglycerides, non-HDL-C, ApoB, LDL particles, VLDL particles, VLDL triglycerides and size (Table). Similar associations were seen in on-treatment rosuvastatin and placebo groups In JUPITER, random allocation to rosuvastatin altered the lipoprotein subclass profile in a manner associated with the development of diabetes Adjusted Hazard Ratios (95% CI) and Risk of Incident Diabetes with Rosuvastatin Baseline parameters HR per 1-SD p value LDL-C .86 (0.76-0.98) .02 HDL-C .69 (0.54-0.87) .002 Triglycerides 1.62 (1.41-1.86) <.0001 Non-HDL-C 1.20 (1.04-1.39) .01 ApoB 1.35 (1.18-1.55) <.0001 Total LDL* 1.32 (1.15-1.51) <.0001 Large LDL* .79 (0.71-0.87) <.0001 Small LDL* 1.71 (1.40-2.08) <.0001 IDL* .97 (0.85-1.11) .69 LDL size .66 (0.58-0.75) <.0001 Total VLDL* 1.16 (1.00-1.34) .046 Large VLDL* 1.78 (1.51-2.10) <.0001 Medium VLDL* 1.35 (1.15-1.58) .0002 Small VLDL* .93 (0.82-1.06) .30 VLDL size 1.58 (1.39-1.80) <.0001 VLDL triglycerides 1.51 (1.31-1.73) <.0001 *particles

scholarly journals Distribution of LDL Particle Size in a Population-Based Sample of Children and Adolescents and Relationship with Other Cardiovascular Risk Factors

2005 ◽  
Vol 51 (7) ◽  
pp. 1192-1200 ◽  
Author(s):  
Simona Stan ◽  
Emile Levy ◽  
Edgard E Delvin ◽  
James A Hanley ◽  
Benoît Lamarche ◽  
...  
Keyword(s):  
Risk Factors ◽  
Particle Size ◽  
Plasma Lipid ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Ldl Particle Size ◽  
Small Dense Ldl ◽  
Ldl Particles ◽  
Ldl Size ◽  
Increased Risk

Abstract Background: Smaller, denser LDL particles are associated with an increased risk for cardiovascular diseases (CVD). In youths, data on the distribution of LDL particle size and on its association with other CVD risk factors are limited. Methods: We determined LDL peak particle size by nondenaturing 2%–16% gradient gel electrophoresis in a representative sample of 2249 youths 9, 13, and 16 years of age who participated in a school-based survey conducted in 1999 in the province of Quebec, Canada. Standardized clinical measurements and fasting plasma lipid, glucose, and insulin concentrations were available. Results: The LDL peak particle size distribution was gaussian. The 5th, 50th (median), and 95th percentiles by age and sex were 255.5–258.6, 262.1–263.2, and 268.1–269.5 Å, respectively. The prevalence of the small, dense LDL phenotype (LDL peak particle size ≤255 Å) was 10% in participants with insulin resistance syndrome (IRS), in contrast to 1% in those without IRS. In a multiple regression analysis, the association of LDL size with other CVD risk factors [apolipoprotein B, HDL-cholesterol (HDL-C), triglyceride (TG), and insulin concentrations, and body mass index] was strongest with TG and HDL-C concentrations: a 1 SD increase in loge-transformed TG concentration was associated with a 1.2 Å reduction in LDL size, and a 1 SD increase in HDL-C was associated with a 1.1 Å increase in LDL size. Conclusions: Although the small, dense LDL phenotype is less prevalent in youths than adults, its prevalence is clearly increased in childhood IRS. Metabolic correlates of LDL size are similar in youths and adults.

scholarly journals Risk Factors for Disability Pension among Young Adults Diagnosed with Attention-deficit Hyperactivity Disorder (ADHD) in Adulthood

2021 ◽  
pp. 108705472110256
Author(s):  
Lingjing Chen ◽  
Ellenor Mittendorfer-Rutz ◽  
Emma Björkenstam ◽  
Syed Rahman ◽  
Klas Gustafsson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Young Adults ◽  
Disability Pension ◽  
Cox Regression ◽  
Related Factors ◽  
Adult Age ◽  
Work Related ◽  
Hyperactivity Disorder ◽  
Increased Risk ◽  
Similar Risk

Objective: To investigate risk factors of disability pension (DP) in young adults diagnosed with ADHD in Sweden. Method: In total, 9718 individuals diagnosed with incident ADHD in young adult age (19–29 years) 2006 to 2011, were identified through national registers. They were followed for 5 years and Cox regression models were applied to analyze the DP risk (overall and by sex), associated with socio-demographics, work-related factors, and comorbid disorders. Results: Twenty-one percent of all received DP. Being younger at diagnosis (hazard ratio [HR] = 1.54; 95%confidence interval [CI] 1.39–1.71); low educational level (HR = 1.97; 95%CI 1.60–2.43 for <10 years); work-related factors at baseline (no income from work [HR = 2.64; 95%CI 2.35–2.98] and sickness absence >90 days [HR = 2.48; 95%CI2.17–2.83]); and schizophrenia/psychoses (HR = 2.16; 95%CI 1.66–2.80), autism (HR = 1.87; 95%CI 1.42–2.46), anxiety (HR = 1.34; 95%CI 1.22–1.49) were significantly associated with an increased risk of DP. Similar risk patterns were found in men and women. Conclusion: Work-related factors and comorbid mental disorders need to be highlighted in early vocational rehabilitation for individuals with ADHD.

scholarly journals Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation study

2021 ◽  
Vol 8 (1) ◽  
pp. e000759
Author(s):  
Daniel Higbee ◽  
Raquel Granell ◽  
Esther Walton ◽  
Roxanna Korologou-Linden ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lung Function ◽  
Causal Relationship ◽  
Mendelian Randomisation ◽  
P Value ◽  
Unmeasured Confounding ◽  
Increased Risk ◽  
Shared Risk

RationaleLarge retrospective case-control studies have reported an association between chronic obstructive pulmonary disease (COPD), reduced lung function and an increased risk of Alzheimer’s disease. However, it remains unclear if these diseases are causally linked, or due to shared risk factors. Conventional observational epidemiology suffers from unmeasured confounding and reverse causation. Additional analyses addressing causality are required.ObjectivesTo examine a causal relationship between COPD, lung function and Alzheimer’s disease.MethodsUsing two-sample Mendelian randomisation, we used single nucleotide polymorphisms (SNPs) identified in a genome wide association study (GWAS) for lung function as instrumental variables (exposure). Additionally, we used SNPs discovered in a GWAS for COPD in those with moderate to very severe obstruction. The effect of these SNPs on Alzheimer’s disease (outcome) was taken from a GWAS based on a sample of 24 807 patients and 55 058 controls.ResultsWe found minimal evidence for an effect of either lung function (OR: 1.02 per SD; 95% CI 0.91 to 1.13; p value 0.68) or liability for COPD on Alzheimer’s disease (OR: 0.97 per SD; 95% CI 0.92 to 1.03; p value 0.40).ConclusionNeither reduced lung function nor liability COPD are likely to be causally associated with an increased risk of Alzheimer’s, any observed association is likely due to unmeasured confounding. Scientific attention and health prevention policy may be better focused on overlapping risk factors, rather than attempts to reduce risk of Alzheimer’s disease by targeting impaired lung function or COPD directly.

scholarly journals Long-term fasting improves lipoprotein-associated atherogenic risk in humans

2021 ◽  
Author(s):  
Franziska Grundler ◽  
Dietmar Plonné ◽  
Robin Mesnage ◽  
Diethard Müller ◽  
Cesare R. Sirtori ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Apolipoprotein A1 ◽  
Health Concern ◽  
Low Density ◽  
Lipoprotein Subclasses ◽  
Ldl Particles ◽  
Increased Risk

Abstract Purpose Dyslipidemia is a major health concern associated with an increased risk of cardiovascular mortality. Long-term fasting (LF) has been shown to improve plasma lipid profile. We performed an in-depth investigation of lipoprotein composition. Methods This observational study included 40 volunteers (50% men, aged 32–65 years), who underwent a medically supervised fast of 14 days (250 kcal/day). Changes in lipid and lipoprotein levels, as well as in lipoprotein subclasses and particles, were measured by ultracentrifugation and nuclear magnetic resonance (NMR) at baseline, and after 7 and 14 fasting days. Results The largest changes were found after 14 fasting days. There were significant reductions in triglycerides (TG, − 0.35 ± 0.1 mmol/L), very low-density lipoprotein (VLDL)-TG (− 0.46 ± 0.08 mmol/L), VLDL-cholesterol (VLDL-C, − 0.16 ± 0.03 mmol/L) and low-density lipoprotein (LDL)-C (− 0.72 ± 0.14 mmol/L). Analysis of LDL subclasses showed a significant decrease in LDL1-C (− 0.16 ± 0.05 mmol/L), LDL2-C (− 0.30 ± 0.06 mmol/L) and LDL3-C (− 0.27 ± 0.05 mmol/L). NMR spectroscopy showed a significant reduction in large VLDL particles (− 5.18 ± 1.26 nmol/L), as well as large (− 244.13 ± 39.45 nmol/L) and small LDL particles (− 38.45 ± 44.04 nmol/L). A significant decrease in high-density lipoprotein (HDL)-C (− 0.16 ± 0.04 mmol/L) was observed. By contrast, the concentration in large HDL particles was significantly raised. Apolipoprotein A1 decreased significantly whereas apolipoprotein B, lipoprotein(a), fibrinogen and high-sensitivity C-reactive protein were unchanged. Conclusion Our results suggest that LF improves lipoprotein levels and lipoprotein subclasses and ameliorates the lipoprotein-associated atherogenic risk profile, suggesting a reduction in the cardiovascular risk linked to dyslipidemia. Trial Registration Study registration number: DRKS-ID: DRKS00010111 Date of registration: 03/06/2016 “retrospectively registered”.

Abstract MP50: Serum Metabolomic Profile of Incident Diabetes

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Casey M Rebholz ◽  
Bing Yu ◽  
Zihe Zheng ◽  
Patrick Chang ◽  
Adrienne Tin ◽  
...  
Keyword(s):  
Fasting Glucose ◽  
Ultra Performance Liquid Chromatography ◽  
Diabetes Risk ◽  
Incident Diabetes ◽  
P Value ◽  
Metabolic Disturbances ◽  
Isoleucine Leucine ◽  
Metabolomics Data ◽  
Metabolomic Profiling ◽  
Increased Risk

Background: Metabolomic profiling offers the potential to reveal metabolic pathways relevant to diabetes pathophysiology and to improve diabetes risk prediction. Methods: We prospectively analyzed metabolites and incident diabetes from baseline (1987-1989) through December 31, 2015 in a subset of 2,939 Atherosclerosis Risk in Communities (ARIC) Study participants with metabolomics data and without diabetes at baseline. Metabolomic profiling was conducted in stored serum specimens collected at baseline using a reverse phase, untargeted ultra-performance liquid chromatography tandem mass spectrometry approach. Results: Among the 245 named compounds we identified, 7 metabolites were significantly associated with incident diabetes after Bonferroni correction and covariate adjustment (age, sex, race, center, batch, education, blood pressures, body mass index, lipids, smoking, physical activity, history of cardiovascular disease, eGFR, fasting glucose). These 7 metabolites consisted of a xenobiotic (erythritol) and compounds involved in amino acid metabolism [isoleucine, leucine, valine, asparagine, 3-(4-hydoxyphenyl)lactate] and glucose metabolism (trehalose). Higher levels of the metabolites were associated with an increased risk of incident diabetes, with the exception of asparagine which was associated with a lower risk of diabetes (HR per 1 SD increase: 0.78, 95% CI: 0.71, 0.85; p=4.19x10 -8 ). The 7 metabolites improved the prediction of incident diabetes beyond fasting glucose and established risk factors (C statistic for model with vs. without 7 metabolites, respectively: 0.744 vs. 0.735; p-value for difference in C statistics=0.001). Conclusions: Branched chain amino acids may play a role in diabetes development. Our study is the first to report asparagine as a protective biomarker of diabetes risk. The serum metabolome reflects known and novel metabolic disturbances that improve diabetes prediction.

scholarly journals Clinical profile and factors determining outcome of intramural very low birth weight babies in a tertiary care centre: a retrospective study

2017 ◽  
Vol 5 (2) ◽  
pp. 520
Author(s):  
Devi Meenakshi K. ◽  
Arasar Seeralar A. T. ◽  
Srinivasan Padmanaban
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Logistic Regression Analysis ◽  
Very Low Birth Weight ◽  
Tertiary Care ◽  
P Value ◽  
Increased Risk

Background: Very low birth weight (VLBW) babies are at increased risk of a number of complications both immediate and late. Worldwide it has been observed that these babies contribute to a significant extent to neonatal mortality and morbidity. Aim of the study was to study the risk factors contributing to mortality in VLBW babies and to evaluate the morbidity pattern in these infants.Methods: A retrospective analysis of data retrieved from the case records of VLBW babies admitted in the NICU of Kilpauk Medical College between January 2015 to December 2015. Out of the 2360 intramural babies admitted during the study period, 99 babies were less than 1500 gms. The risk factors for these babies were analyzed for their association with the outcome. Data were statistically analyzed.Results: In present study, we found that sex of the baby, gestational age, obstetric score, birth asphyxia, pulmonary haemorrhage, ROP and presence of shock were found to be associated with increased mortality. By logistic regression analysis it was observed that birth weight of the baby (p value 0.002), duration of stay (p value 0.0006), presence of shock (p<0.0001), were the risk factors significantly associated with poor outcome.Conclusions: Among the maternal and neonatal factors analyzed in the study using logistic regression analysis, birth weight, duration of hospital stay and presence of shock were significantly related to poor outcome. Of these presence of shock was the single most important factor that predicted increased mortality.

scholarly journals COMPUTER VISION SYNDROME: PREVALENCE AND ASSOCIATED RISK FACTORS AMONG UNDERGRADUATES IN A TERTIARY INSTITUTION IN NORTH WESTERN NIGERIA

2021 ◽  
Vol 15 (1) ◽  
pp. 1-8
Author(s):  
Nwankwo B ◽  
◽  
Mumueh KP ◽  
Olorukooba AA ◽  
Usman NO
Keyword(s):  
Risk Factors ◽  
Computer Vision ◽  
Computer Use ◽  
P Value ◽  
Tertiary Institution ◽  
Blurred Vision ◽  
Cross Sectional ◽  
Computer Vision Syndrome ◽  
Increased Risk ◽  
Associated Risk Factors

Background: Computers and other visual display devices have become essential in the present era and have led to a rise in computer-related health problems. Using computers in homes, universities and other institutions has increased output greatly but has also led to an increased risk of developing Computer vision syndrome (CVS). Objectives: To determine the prevalence and risk factors associated with computer vision syndrome among undergraduates. Methodology: A cross-sectional study was conducted among153 respondents who were selected using a multi-stage sampling technique. A pretested, structured, interviewer-administered questionnaire was used to collect data. SPSS version 23 was used to analyze the data. A Chi-square test was used to determine the relationship between CVS and associated risk factors at a P-value of <0.05. Results: The mean age of respondents was 22.4 ± 3.4 years. The prevalence of CVS in this study was 83 (54.3%). The common symptoms experienced among the respondents were headache (51, 61.4%), eye strain (48, 57.8%) and blurred vision (42, 50.6%). The risk factors significantly associated with CVS in this study were duration of computer use, hours of computer use per day, level of a computer screen and taking breaks during computer use. Conclusion: About half of the students in this study had at least one symptom of CVS. Therefore, awareness of CVS should be created by the institution during which students would be educated on CVS and its prevention.

scholarly journals Morbidity and mortality outcomes of COVID-19 patients with and without hypertension in Lagos, Nigeria: A retrospective cohort study

2020 ◽  
Author(s):  
Akin Osibogun ◽  
Akin Abayomi ◽  
Oluchi Kanma-Okafor ◽  
Jide Idris ◽  
Abimbola Bowale ◽  
...  
Keyword(s):  
Cohort Study ◽  
Critical Illness ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Cox Regression ◽  
Outcome Data ◽  
Morbidity And Mortality ◽  
P Value ◽  
Hypertensive Patients ◽  
Increased Risk

Abstract Background: The current pandemic of coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown epidemiological and clinical characteristics that appear worsened in hypertensive patients. The morbidity and mortality of the disease among hypertensive patients in Africa have yet to be well described.Methods: In this retrospective cohort study all confirmed COVID-19 adult patients (≥18 years of age) in Lagos between February 27 to July 6 2020 were included. Demographic, clinical and outcome data were extracted from electronic medical records of patients admitted at the COVID-19 isolation centers in Lagos. Outcomes included dying, being discharged after recovery or being evacuated/transferred. Descriptive statistics considered proportions, means and medians. The Chi-square and Fisher’s exact tests were used in determining associations between variables. Kaplan–Meier survival analysis and Cox regression were performed to quantify the risk of worse outcomes among hypertensives with COVID-19 and adjust for confounders. P-value ≤0.05 was considered statistically significant.Results: A total of 2075 adults with COVID-19 were included in this study. The prevalence of hypertension, the most common comorbidity, was 17.8% followed by diabetes (7.2%) and asthma (2.0%). Overall mortality was 4.2% while mortality among the hypertensives was 13.7%. Severe symptoms and mortality were significantly higher among the hypertensives and survival rates were significantly lowered by the presence of an additional comorbidity to 50% from 91% for those with hypertension alone and from 98% for all other patients (P<0.001). After adjustment for confounders (age and sex), severe COVID-19and death were higher for hypertensives {severe/critical illness: HR=2.41, P=0.001, 95%CI=1.4–4.0, death: HR=2.30, P=0.001, 95%CI=1.2–4.6, for those with hypertension only} {severe/critical illness: HR=3.76, P=0.001, 95%CI=2.1–6.4, death: crude HR=6.63, P=0.001, 95%CI=3.4–1.6, for those with additional comorbidities}. Hypertension posed an increased risk of severe morbidity (approx. 4-fold) and death (approx. 7-fold) from COVID-19 in the presence of multiple comorbidities. Conclusion: The potential morbidity and mortality risks of hypertension especially with other comorbidities in COVID-19 could help direct efforts towards prevention and prognostication. This provides the rationale for improving preventive caution for people with hypertension and other comorbidities and prioritizing them for future antiviral interventions.

Abstract P036: Effects of Exercise Training and Increasing Non-Exercise Physical Activity on Lipoprotein Subclass and Size: Results From the I-CAN Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Damon L Swift ◽  
Mark A Sarzynski ◽  
Joshua McGee ◽  
Savanna Barefoot ◽  
Patricia M Brophy ◽  
...  
Keyword(s):  
Physical Activity ◽  
Exercise Training ◽  
Aerobic Training ◽  
Analysis Of Covariance ◽  
Control Group ◽  
Resonance Spectroscopy ◽  
Lipoprotein Subclass ◽  
Lipoprotein Subclasses ◽  
Ldl Particles ◽  
The Impact

Introduction: Previous studies have shown that lipoprotein particle size and lipoprotein subclasses are associated with cardiovascular and type 2 diabetes risk, and have independent prognostic value above traditional lipid concentrations. The impact of exercise training and increasing non-exercise physical activity on lipoprotein subclasses and size has not been previously investigated. Methods: In this pilot study, 35 obese adults were randomized to aerobic exercise training (50-75% of VO 2 max) (AERO, n=11), aerobic training and increasing non-exercise physical activity (AERO-PA, n=10, ~3,000 steps above baseline levels), or a non-exercise control group (n=14) for 6 months. Baseline and follow-up blood samples were analyzed for lipoprotein subclass, size, and lipoprotein insulin resistance score (LP-IR) using nuclear magnetic resonance spectroscopy (Liposcience, NC). Analysis of covariance was used to evaluate the change in outcome variables following the intervention across groups with adjustment for baseline value and age. Participants who changed lipid medications during the intervention (n=2) or who were non-adherent to exercise training (n=2) were excluded from the analysis. Results: Significant reductions were observed for mean VLDL size in the AERO-PA group (-4.7 nm, CI: -8.7 to -0.8) compared to control group (0.7 nm, CI: -2.7 to 4.4) and the AERO group (1.1 nm, CI: -2.9 to 5.0). Reductions in triglyceride concentrations were observed in the AERO-PA group (-28.3 mg/dL, CI: -50.3 to -6.4) compared to control (4.1 mg/dL, CI: -14.6 to 22.8). Additionally, we observed a trend for LP-IR index (p=0.055) and the concentration of small HDL particles (p=0.093) to decrease in the AERO-PA group compared to controls, with no differences compared to the AERO group (p>0.10). No significant changes were observed for other notable lipoprotein measures, such as LDL size, HDL size, concentration of small LDL particles, or chylomicron measures (p>0.05). In the AERO-PA group, the change in steps was associated with the change in LP-IR index (r= -0.71, p=0.013), but not with change in VLDL size (r= -0.24, p=0.463) or triglyceride concentrations (r=-0.28, p=0.388). Conclusions: Aerobic training combined with increasing non-exercise physical activity leads to favorable changes in the lipoprotein profile, specifically reductions in VLDL size and triglycerides, and may have promise for other lipoprotein traits (reductions in LP-IR and small HDL particles) that were not observed with aerobic training alone.

Abstract P060: Plasma Osteocalcin And Incident Diabetes Mellitus: The Atherosclerosis Risk In Communities (ARIC) Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Jeffrey R Misialek ◽  
Elizabeth R Stremke ◽  
Elizabeth Selvin ◽  
Sanaz Sedaghat ◽  
James S Pankow ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cox Regression ◽  
Self Report ◽  
Incident Diabetes ◽  
Blood Levels ◽  
Total Plasma ◽  
Phone Calls ◽  
Increased Risk ◽  
Primary Model

Introduction: Diabetes is a major risk factor for cardiovascular disease. Osteocalcin is a vitamin K-dependent, bone-derived hormone that functions as an endocrine regulator of energy metabolism, male fertility, and cognition. Early studies of endocrine effects of osteocalcin have shown that genomic deletion of osteocalcin in mice resulted in a diabetic phenotype (i.e. glucose intolerance, and insulin resistance). However, results from clinical studies have shown mixed associations between blood levels of osteocalcin and risk of incident type 2 diabetes mellitus. Hypothesis: Lower values of plasma osteocalcin would be associated with an increased risk of diabetes. Methods: A total of 11,557 ARIC participants without diabetes at baseline were followed from ARIC visit 3 (1993-1995) through 2018. Diabetes cases were identified through self-report on annual and semi-annual follow-up phone calls. Plasma osteocalcin data was measured using an aptamer-based proteomic profiling platform (SomaLogic). We used Cox regression to evaluate the association of quintiles of plasma osteocalcin and incident diabetes. The primary model adjusted for age, sex, and race-center. Results: Participants were age 60 ± 5.6 years at visit 3, 56% identified as female, 21% identified as Black. There were 3,031 incident diabetes cases over a median follow-up of 17.9 years. Mean ± SD was 10.053 ± 0.775. When comparing the highest quintile of plasma osteocalcin (values 10.42 to 14.66) to the lowest quintile (values 9.03 to 9.52), there was no association with incident diabetes (HRs [95% CIs]: 0.92 [0.81, 1.02]). There was also no significant trend across the quintiles (p = 0.19). Results were similar when adjusting for additional potential confounders, and when limiting the follow-up time to 10 years. Conclusions: These data do not support the hypothesis that total plasma osteocalcin, as measured by Somalogic proteomic panel, is a biomarker associated with diabetes risk. It is possible that total plasma or serum osteocalcin and/or other isoforms of osteocalcin protein (i.e. gamma carboxylated or uncarboxylated osteocalcin) measured via other validated methodologies may be linked to diabetes.

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