Coronary Artery Calcification In Type Research Articles

Longitudinal Three-Year Associations of Dietary Fruit and Vegetable Intake with Serum hs-C-Reactive Protein in Adults with and without Type 1 Diabetes.

High-sensitivity C-reactive protein (hs-CRP) is a widely used clinical biomarker of systemic inflammation, implicated in many chronic conditions, including type 1 diabetes (T1D). Despite the increasing emphasis on dietary intake as a modifiable risk factor for systemic inflammation, the association of hs-CRP with fruit and vegetable consumption is relatively underexplored in T1D. To address this gap, we investigated the longitudinal associations of dietary pattern-derived fruit and vegetable scores with hs-CRP in adults with and without T1D. Additionally, we examined the impact of berry consumption as a distinct food group. Data were collected in the Coronary Artery Calcification in Type 1 Diabetes study over two visits that were three years apart. At each visit, participants completed a food frequency questionnaire, and hs-CRP was measured using a particle-enhanced immunonephelometric assay. Mixed effect models were used to examine the three-year association of fruit and vegetable scores with hs-CRP. Adjusted models found a significant inverse association between blueberry intake and hs-CRP in the nondiabetic (non-DM) group. Dietary Approaches to Stop Hypertension- and Alternative Healthy Eating Index-derived vegetable scores were also inversely associated with hs-CRP in the non-DM group (all p-values ≤ 0.05). Conversely, no significant associations were observed in the T1D group. In conclusion, dietary pattern-derived vegetable scores are inversely associated with hs-CRP in non-DM adults. Nonetheless, in T1D, chronic hyperglycemia and related metabolic abnormalities may override the cardioprotective features of these food groups at habitually consumed servings.

Carotid intima layer thickness but not intima-media thickness is related to coronary artery calcification in type 2 diabetes individuals: Results from the Brazilian diabetes study

Background and aimsCarotid intima-media thickness (cIMT) is inconsistent in predicting cardiovascular risk. This may stem from the variability of the media thickness (cM) outweighing the intimal thickness (cIT) as the sign of atherosclerosis. Thus, we evaluated in type 2 diabetes (T2D) individuals, the association between carotid measures and coronary artery calcification (CAC). Methods and resultsAssociation between the presence of CAC and cIT, cM, and cIMT were examined on 224 individuals. Logistic binary regression was used to assess CAC predictors. The Akaike information criterion (AIC) and log-likelihood test (LLT) were used to assess differences among univariate models. The cIT (0.335 mm vs 0.363 mm; p = 0.001) and cIMT (0.715 vs 0.730; p = 0.019), but not cM (0.386 mm vs 0,393 mm; p = 0.089) were higher among individuals with CAC. In unadjusted analysis, cIT (273;-134; p = 0.001) showed greater relationship with CAC, when compared to cIMT (279;-137; p = 0.022) and cM (281;-139; p = 0.112) based on the AIC and LLT, respectively. In multivariate logistic regression, CAC was related to carotid plaque (OR): 1.91, 95% confidence interval (CI):1.08, 3.38; p = 0.027), and high-cIT (OR: 2.70, 95%CI:1.51, 4.84; p = 0.001), but not to high-cIMT (OR:1.70, 95%CI:0.96, 3.00; p = 0.067) nor high-cM (OR:1.33, 95%CI:0.76, 2.34; p = 0.322). ConclusionIn T2D individuals, cIT is a better predictor of CAC than cIMT; cM is not associated with CAC.

414-P: Multiomic Plasma Markers of Diabetic Kidney Disease in Type 1 Diabetes

Diabetic kidney disease (DKD) is a major complication of type 1 diabetes (T1D). We investigated whether metabolomic, lipidomic and proteomic plasma markers were associated with albuminuria in the Coronary Artery Calcification in Type 1 Diabetes cohort. Two timed overnight urine collections were performed, and albumin excretion rates (AER) were averaged. If overnight samples were unable to be obtained, a spot urine sample was collected and albumin/creatinine ratio (ACR) was used to determine albuminuria status. Albuminuria was defined as an AER ≥ 20 ug/min or an ACR ≥ 30mg/g. Plasma samples from the baseline examination were assayed by LC-MS for multiple omics markers in 225 participants with T1D. Moderated t-tests using false discovery rate (FDR) adjustment for multiple comparisons were used to examine the markers associated with albuminuria presence. An FDR adjusted p-value <0.05 was considered to be statistically significant. Average ± SD for age was 36 ± 9 years and for diabetes duration was 23 ± 9 years, and 58% [n = 120] were female. The prevalence of albuminuria at baseline was 20.4% (n = 46). There were 15 metabolite markers (3 metabolites of symmetric dimethylarginine, 2 of glycyl-glycine, and one each of aspartyl-glycine, glycyl-aspartate and 1-methylhistidine, 7 uncertain) with higher expression in participants with DKD than in those without DKD. There were 7 lipid markers in the acylcarnitine family that were elevated in participants with DKD compared to those without DKD, and 19 glycated peptides (16 in fibrinogen, 1 in kininogen and 1 in hemopexin) showed higher expression in participants with DKD than in those without DKD. None of the unmodified proteins differed by DKD status. Multiple omics markers were higher in T1D participants with albuminuria than in people without any sign of DKD. These findings may suggest changes in lipids, metabolites and glycated proteins early in the course of DKD, and these markers should be explored as potential predictors of worsening DKD. Disclosure J.K.Snell-bergeon: None. R.K.Johnson: None. L.Pyle: None. G.Chen: None. M.M.Weldemariam: None. Q.Zhang: None.

1374-P: Ultra-processed Food Consumption and Cardiometabolic Risk in Individuals With and Without Type 1 Diabetes Mellitus

Background: Ultra-processed foods (UPFs) contribute to almost 60% of energy intake in the American diet. The longitudinal association between UPF consumption and cardiometabolic risk is less known, especially in people with type 1 diabetes mellites (T1DM) who are at a higher risk of developing cardiometabolic diseases than people without diabetes (non-DM). Methods: We performed a longitudinal analysis of data from the Coronary Artery Calcification in Type 1 Diabetes study (T1DM: n=652; non-DM: n=764) collected at baseline and years 3, 6, and 14. Baseline age was 37.8±9.3 years. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire, and cardiometabolic biomarkers (BMI, waist circumference, triglycerides, HDL-C, LDL-C, and systolic and diastolic blood pressure) were measured at all four time points. NOVA food classification was used to compute UPF consumption (servings/d). Linear mixed-effects models were used to estimate longitudinal associations of UPF consumption with cardiometabolic risk, adjusting for potential confounders (race, age, sex, education, physical activity, smoking, energy intake, antihypertensive and lipid-lowering drugs, and diabetes duration for T1DM). Results: People with T1DM consumed more UPFs, including processed meat, soft drinks, salty snacks, and margarine, than non-DM at baseline (8.7±7.8 vs. 7.3±6.7 servings/d, P<0.01). Higher UPF consumption was associated with higher anthropometric measures (BMI: β=0.01±0.01, waist circumference: β=0.03±0.01), worse lipid levels (triglycerides: β=0.21±0.09, HDL-C: β=-0.04±0.02), and higher systolic blood pressure (β=0.05±0.02) when adjusted for diabetes status and other covariates (all P<0.05). Conclusion: UPF consumption significantly worsened the cardiometabolic profile over time in people with and without T1DM. Decreasing UPF intake may reduce the risk of developing cardiometabolic diseases across the lifespan. Disclosure T.Pang: None. A.C.Alman: None. H.L.Gray: None. G.Dagne: None. A.Basu: None. A.W.Buro: None. J.K.Snell-bergeon: None. Funding American Diabetes Association (7-13-CD-10 to J.K.S-B.), (7-13-CE-02 to A.C.A.); National Heart, Lung, and Blood Institute (R01HL079611, R01HL113029); Diabetes Endocrinology Research Center (P30DK57516, P30DK1116073)

Longitudinal Associations of Healthy Dietary Pattern Scores with Coronary Artery Calcification and Pericardial Adiposity in United States Adults with and without Type 1 Diabetes

BackgroundPericardial adipose tissue volume (PAT) and coronary artery calcification (CAC) are prognostic indicators for future cardiovascular events; however, no studies have assessed the long-term associations of adherence to dietary patterns (DPs) with PAT and CAC in adults with and without type 1 diabetes (T1D). ObjectivesWe investigated the longitudinal associations of the Mediterranean Diet (MedDiet) and Dietary Approaches to Stop Hypertension (DASH) diet with PAT and CAC progression in adults with and without T1D. MethodsThe Coronary Artery Calcification in Type 1 Diabetes (CACTI) study is a population-based, prospective study of 652 T1D and 764 nondiabetic mellitus (nonDM) (19–56 y) participants that began in 2000–2002 with follow-up visits in 2003–2004 and 2006–2007. At each visit, food frequency questionnaires were collected and used to develop adherence scores for the MedDiet and DASH diets. PAT and CAC were measured at each visit using electron beam computed tomography. CAC progression was defined as a ≥2.5 mm square root-transformed volume. Mixed effect models were used to conduct statistical analyses. ResultsCombined models found a significant–0.09 cm3 (95% CI: −0.14, −0.03; P = 0.0027) inverse association in PAT for every 1-point increase in the MedDiet score and a significant–0.26 cm3 (95% CI: −0.38, −0.14; P < 0.0001) inverse association in PAT for every 1-point increase in the DASH score. In combined models, the DPs were not significantly associated with lower odds of CAC progression; however, both DPs had significant interactions by diabetes status for CAC. Only the DASH diet was associated with lower odds of CAC progression in the nonDM group (OR: 0.96; 95% CI: 0.93, 0.99; P = 0.0224). ConclusionsThese data suggest that the DPs are associated with lower PAT, which may reduce future cardiovascular events. The DASH diet may be beneficial for lower odds of CAC progression in those without T1D.

Periodontitis and cardiovascular risk factors in subjects with and without type 1 diabetes: A cross sectional analysis

AimsThis cross-sectional analysis explored the relationships between periodontal disease (PD) and subclinical CVD in a cohort of patients with type 1 diabetes and non-diabetic controls. MethodsData were collected from adults enrolled in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study or enrolled through the Barbara Davis Center for Diabetes Adult Clinic. A clinical periodontal exam measured attachment loss and probing depth. Brachial artery distensibility (brachD), carotid intima-media thickness (cIMT), and pulse wave velocity (PWV) were assessed as measures of subclinical cardiovascular structure and function. Results144 participants with T1D and 148 non-diabetics were enrolled. Compared to non-diabetic controls, T1D participants had a higher probing depth (2.6 mm vs. 2.5 mm; p = 0.04), higher attachment loss (2.7 mm vs. 2.4 mm; p < 0.01), lower brachD (mean 5.8 vs. 6.4 mmHg; p < 0.01), a higher cIMT (mean 0.68 vs. 0.64 mm; p < 0.01), and a higher PWV (mean 8.3 vs. 7.8 m/s; p < 0.01). There were no significant associations between PD and CVD metrics. ConclusionsPeriodontal and cardiovascular health was worse in participants with T1D compared to non-diabetics. No significant associations between PD measures and CVD were identified.

Ultra-processed food consumption and obesity indicators in individuals with and without type 1 diabetes mellitus: a longitudinal analysis of the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) cohort study.

To evaluate the associations of ultra-processed food (UPF) consumption and obesity indicators among individuals with and without type 1 diabetes mellitus (T1DM) from the Coronary Artery Calcification in Type 1 Diabetes cohort study. A secondary analysis. The consumption of UPF was assessed using the dietary data collected with the Harvard FFQ, and each food item was categorised according to the NOVA food processing classification. Height, weight and waist circumference were measured at baseline and after a mean of 14·6-year follow-up. Generalised estimating equations stratified by diabetes status were used to assess the associations between UPF intake and obesity indicators over 14 years of follow-up. USA. A total of 600 adults (256 T1DM and 344 non-diabetic controls) aged 39 ± 9·1 years at baseline and followed up for over 14 years were included. Participants with T1DM consumed significantly more UPF than non-diabetic controls at baseline: 7·6 ± 3·8 v. 6·6 ± 3·4 servings per day of UPF, respectively (P < 0·01). Participants with T1DM and with the highest UPF intake had the highest weight (βQ4 v. Q1 = 3·07) and BMI (βQ4 v. Q1 = 1·02, all P < 0·05) compared with those with the lowest UPF intake. Similar positive associations were observed in non-diabetic controls. Individuals with T1DM may consume more UPF than non-diabetic controls. Positive associations between UPF consumption and obesity indicators suggest that limiting UPF can be recommended for obesity prevention and management. Further research is needed to confirm these findings.

Correlation between osteoprotegerin and coronary artery calcification in diabetic subjects: a systematic review of observational studies

Coronary artery calcification (CAC) is one of the critical cardiovascular complications that lead to elevated morbidity and mortality among patients with type 2 diabetes (T2M). The association between osteoprotegerin (OPG) and CAC could potentially provide a reasonable chance for preventive therapy in type 2 diabetic patients and benefit the rate of mortality. Since measurement of CAC score is relatively expensive and requires radiation exposure, the current systematic review aims to provide clinical evidence for evaluating the prognostic role of OPG in determining CAC risk among subjects with T2M. Web of Science, PubMed, Embase, and Scopus, were investigated until July 2022. We assessed human studies investigating the association of OPG with CAC in type 2 diabetic patients. Quality assessment was performed by Newcastle–Ottawa quality assessment scales (NOS). Out of 459 records, 7 studies remained eligible to be included. Observational studies that provided odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between OPG and the risk of CAC were analyzed by random-effects model. In order to provide a visual summary of our findings, the estimation of pooled OR from cross-sectional studies was reported as 2.86 [95% CI 1.49–5.49], which is consistent with the findings of the cohort study. Results revealed that the association between OPG and CAC was significant among diabetic patients. OPG is hypothesized to be a potential marker in predicting the presence of high coronary calcium score among subjects with T2M that could be recognized as a novel target for further pharmacological investigations.

Associations of the Mediterranean-Style Dietary Pattern Score with Coronary Artery Calcification and Pericardial Adiposity in a Sample of US Adults.

Several studies have identified improvements in the risks of cardiovascular disease in adults following a Mediterranean dietary pattern. However, data are scarce on its association with coronary artery calcification (CAC) and pericardial adiposity (PAT) in US adults with and without diabetes. To address this gap, we conducted a case-control study using baseline data from the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study [n = 1255; Type 1 Diabetes (T1D): n = 563; non-Diabetes Mellitus (non-DM): n = 692]. Participants completed a validated food frequency questionnaire, fasting (12 h overnight fast) biochemical analyses, and a physical examination including anthropometric measures. CAC and PAT were measured using electron beam-computed tomography. Logistic regression models were used to examine the associations of the Mediterranean-Style Dietary Pattern Score (MSDPS) with CAC (presence or absence), and linear regression models were applied to PAT analyses. In all of the adjusted models, no significant associations with CAC were found. For PAT, an increasing MSDPS was consistently associated with its lower volume in models adjusted for age, sex, diabetes status, total calories, and body mass index (all p < 0.05). The association between MSDPS and PAT was attenuated after adjusting for serum lipids and physical activity. In conclusion, the baseline data from the CACTI study show that a greater adherence to MSDPS is associated with a lower PAT volume and provide evidence that the Mediterranean dietary pattern is associated with lower cardiovascular risk markers.

Associations of Dietary Antioxidants with Glycated Hemoglobin and Insulin Sensitivity in Adults with and without Type 1 Diabetes.

Type 1 diabetes (T1D) has been associated with increased risks of atherosclerotic cardiovascular disease, and poor glycemic control and oxidative stress play a major role in its pathology. There is a lack of data on the role of dietary antioxidant micronutrients, including vitamins and trace elements, in glycemic control in T1D. The aim of this study is to examine associations of dietary intakes of micronutrients with glycemic status. We report data from a cross-sectional analysis from the coronary artery calcification in type 1 diabetes (CACTI) study (n = 1257; T1D: n = 568; nondiabetic controls: n = 689) collected between the years 2000 and 2002. Participants completed a validated food frequency questionnaire, a physical examination, and biochemical analyses. Linear regression was used to examine the associations of dietary antioxidant micronutrients with HbA1c and estimated insulin sensitivity (eIS) in models adjusted for relevant covariates and stratified by diabetes status. In adults with T1D, we observed higher dietary manganese intake associated with higher eIS in the model adjusted for age, sex, diabetes duration, and total calories. In nondiabetic controls, higher intake of manganese associated with lower HbA1c and higher eIS values that persisted in models adjusted for all relevant covariates. On the other hand, dietary copper revealed a positive association with HbA1c in models adjusted for all covariates, except BMI and plasma lipids. No associations were noted for vitamins C and E and dietary carotenoids in either group. These findings reveal dietary antioxidant micronutrients, especially trace elements such as copper and manganese deserve special attention in glycemic control in adults with T1D as well as in nondiabetic controls.This trial is register with NCT00005754.

99-OR: HbA1c Variability Predicts Both Coronary Atherosclerosis and CVD Events in Type 1 Diabetes

Introduction: Interventions that decrease mean glucose have reduced rates of type 1 diabetes (T1D) vascular complications, but the difference in cardiovascular disease (CVD) risk between people with T1D and the general population endures. This suggests that factors beyond hemoglobin A1c (HbA1c) normalization may drive T1D CVD outcomes. HbA1c variability is an established predictor of T1D microvascular disease, but thus far only the FinnDiane Study has implicated it as a risk factor for T1D CVD events. No studies have examined the relationship of HbA1c variability to both CVD risk factors and events in a prospective T1D cohort. Methods: We used multivariable logistic regression to analyze the Coronary Artery Calcification in Type 1 Diabetes (CACTI) T1D cohort (N=597) . Primary outcomes were square root-transformed coronary artery calcium (CAC) volume and CVD events. CVD events were defined as myocardial infarction, coronary artery bypass grafting, angioplasty, or cardiovascular death. HbA1c variability was defined as a 1-standard deviation increment in HbA1c and calculated as standard deviation of all HbA1c values for each subject. Results: After adjustment for age, sex, and T1D duration, HbA1c variability predicted both CVD events (HR: 1.562, 95% CI: 1.052-2.318, P=0.0269) and CAC volume (rpartial= 0.3346, P&amp;lt;0.001) , while mean HbA1c predicted CVD events (HR: 1.399, 95% CI: 1.079-1.816, P=0.0114) but not CAC volume (rpartial= 0.0934, P=0.2886) . Further investigation revealed that the relationship between HbA1c variability and CVD events was strongest in those with good glycemic control (HR: 6.330 at mean HbA1c of 6.0%, HR: 3.920 at mean HbA1c of 7.0%, HR: 2.428 at mean HbA1c of 8.0%, HR: 1.5at mean HbA1c of 9.0%, and HR: 0.931 at mean HbA1c of 10.0%) . Conclusion: HbA1c variability may be a risk factor for both coronary atherosclerosis and CVD events in T1D, and the appropriate care strategy for this population may include maintaining an HbA1c value over time that is both at-target and stable. Disclosure W.B.Horton: None. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc. Funding National Institutes of Health (R01DK116731) National Institutes of Health (R01HL113029)

98-OR: Prediction of Cardiovascular Disease in People with Type 1 Diabetes with Novel Omics Biomarkers

Introduction: Type 1 diabetes (T1D) increases risk for cardiovascular disease (CVD) at least 2-4 fold, with only half the excess risk explained by known risk factors. We sought to identify novel proteomic, lipidomic, and metabolomic biomarkers of CVD in T1D. Methods: We first built a predictive model of coronary artery calcium progression (CACp) using LASSO regression of clinical variables measured at baseline in 365 participants with T1D in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. The selected model was refit to a subgroup of 102 participants with complete clinical information and measured omics markers (targeted and untargeted metabolomics, global proteomics, glycated proteomics, and lipidomics) . Omics biomarkers were identified for inclusion in the final model by retaining the top markers that predicted CACp by moderated t-tests and sPLS-DA models. Results: The table shows variables retained in the clinical model (AUC=0.91) and in the model with biomarkers added (AUC=0.94) . Higher age, urine albumin:creatinine, and insulin dose predicted CACp in both models. Longer duration of T1D predicted CACp in the clinical model. In the model with D-Glucosamine/D-galactosamine and glycated fibrinogen peptides, D-Glucosamine/D-Galactosamine predicted CACp. Conclusion: Novel metabolites improved prediction of CACp in people with T1D. Disclosure L.Pyle: None. T.B.Vigers: None. R.K.Johnson: None. Q.Zhang: None. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc. Funding American Heart Association (17CSA33570025) , NIH (P30-DK116073)

Cross-Sectional Associations of Fruit and Vegetable Intake with Coronary Artery Calcification and Pericardial Adiposity

ObjectivesTo examine the associations between fruit and vegetable (F&V) scores derived from the Mediterranean Diet (MedDiet) and Healthy Eating Index (HEI, 2015) with coronary artery calcification (CAC) and pericardial adiposity (PAT) in adults with and without type 1 diabetes (T1D).MethodsWe conducted a cross-sectional analysis of baseline data from the Coronary Artery Calcification in Type 1 Diabetes study [n = 1255; T1D: n = 563; non-DM: n = 692]. Participants completed a validated food frequency questionnaire, a physical examination, and fasting (12 h overnight fast) biochemical analyses. CAC and PAT were measured using electron beam computed tomography. Logistic regression models examined associations of F&V scores with CAC (presence or absence) and linear regression models were applied to PAT analyses. Model 1 was adjusted for age, sex and diabetes status, model 2 added total calories, and model 3 added BMI and lipids (LDL and HDL-cholesterol).ResultsF&V scores had no associations with CAC in any of these models. In models 1 and 2, a one-point increase in the MedDiet-derived total fruit score was associated with a significant −1.79% (95% CI: (−0.03, −0.01); p-value = 0.0001) decrease in PAT. In model 3, a one-point increase in the MedDiet-derived total fruit score was associated with a borderline significant decrease of −0.74% (95% CI: (−0.01, 0.00); p-value = 0.054) in PAT. In models 1 and 2 for the HEI-derived total fruit score, a one-point increase in the total fruit score was associated with a significant −3.22% (95% CI: (−0.05, −0.01); p-value = 0.0012) decrease in PAT. In model 3 for the HEI-derived total fruit score, there was no significant association between the HEI-derived total fruit score and PAT (p-value = 0.140).ConclusionsBaseline analyses show MedDiet and HEI-derived total fruit scores maintained a significant to borderline significant inverse relationship with PAT, but F&V scores were not associated with presence of CAC.Funding SourcesNIH and ADA.

Abstract 445: Pulmonary Surfactant Protein B Carried By HDL Is Associated With Incident Cardiovascular Disease In Patients With Type 1 Diabetes

Atherosclerotic cardiovascular disease (CVD) is the major cause of death in people with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome associate with prevalent CVD in T1DM. We therefore determined which proteins carried by HDL are associated with incident CVD in T1DM patients. We conducted a case-cohort study of incident CVD in the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. We randomly sampled 145 CACTI participants without prevalent CVD, 11 of whom subsequently developed a CVD event as a cohort, plus all additional T1DM participants in CACTI (N=36) who developed an incident CVD event (a total of 47 CVD cases). Using targeted MS/MS, we quantified 51 proteins in HDL isolated from baseline plasma samples. We used Cox proportional regression analysis and a case-cohort design to test associations of HDL proteins with incident CVD (myocardial infarction, coronary artery bypass grafting, angioplasty, or death from coronary heart disease). Only one HDL protein—SFTPB (pulmonary surfactant protein B)—was associated with incident CVD in T1DM in all of the models tested. In a fully adjusted model that controlled for smoking status, lipids and other risk factors, the hazard ratio was 2.17 per SD increase of SFTPB (95% confidence interval, 1.12-4.21, P=0.022). Plasma fractionation and targeted MS/MS quantification demonstrated that nearly 95% of plasma SFTPB is quantitatively bound to HDL. Our results show that elevated levels of SFTPB in HDL are strongly associated with incident CVD in CACTI subjects with T1DM independently of smoking status and a wide range of other confounding factors. Because HDL is the major carrier of SFTPB in plasma, our observations support the proposal that SFTPB carried by HDL is a novel marker of CVD risk in patients with T1DM.

HDL, heart disease, and the lung

HDL, heart disease, and the lung

Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes

Atherosclerotic CVD is the major cause of death in patients with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome have been shown to associate with prevalent CVD in T1DM. We therefore sought to determine which proteins carried by HDL might predict incident CVD in patients with T1DM. Using targeted MS/MS, we quantified 50 proteins in HDL from 181 T1DM subjects enrolled in the prospective Coronary Artery Calcification in Type 1 Diabetes study. We used Cox proportional regression analysis and a case-cohort design to test associations of HDL proteins with incident CVD (myocardial infarction, coronary artery bypass grafting, angioplasty, or death from coronary heart disease). We found that only one HDL protein—SFTPB (pulmonary surfactant protein B)—predicted incident CVD in all the models tested. In a fully adjusted model that controlled for lipids and other risk factors, the hazard ratio was 2.17 per SD increase of SFTPB (95% confidence interval, 1.12–4.21, P = 0.022). In addition, plasma fractionation demonstrated that SFTPB is nearly entirely bound to HDL. Although previous studies have shown that high plasma levels of SFTPB associate with prevalent atherosclerosis only in smokers, we found that SFTPB predicted incident CVD in T1DM independently of smoking status and a wide range of confounding factors, including HDL-C, LDL-C, and triglyceride levels. Because SFTPB is almost entirely bound to plasma HDL, our observations support the proposal that SFTPB carried by HDL is a marker—and perhaps mediator—of CVD risk in patients with T1DM.

Empirical dietary inflammatory pattern and metabolic syndrome: prospective association in participants with and without type 1 diabetes mellitus in the coronary artery calcification in type 1 diabetes (CACTI) study

The inflammatory potential of diet, assessed by Empirical Dietary Inflammatory Pattern (EDIP), may play a crucial role in the development of metabolic syndrome (MetS). However, limited research on this relationship is available. We hypothesized that EDIP is positively associated with MetS and its components. This longitudinal study included 1177 participants (526 with type 1 diabetes mellitus [T1DM] and 651 without) from the Coronary Artery Calcification in Type 1 Diabetes study. Dietary assessment and anthropometric and biochemical measurements were assessed at baseline and 14-year follow-up. MetS status was defined using the Harmonization criteria. EDIP scores were computed based on a food frequency questionnaire. Generalized linear mixed models were applied and subgroup analyses were performed by diabetes status. Mean age of study participants was 38 years and 48% were male at baseline. EDIP was positively associated with MetS (βT3 versus T1=0.81, P < .01) in T1DM but not in nondiabetic controls. Of the MetS components, low HDL-C and hypertriglyceridemia had positive associations with EDIP in both groups. Individuals with T1DM consumed more pro-inflammatory diets and had a greater risk of developing MetS than those without diabetes. The consumption of processed meat, red meat, high- and low- energy beverages was significantly higher in those with MetS than those without this condition (all P < .05). Reduced consumption of pro-inflammatory foods such as processed meat, red meat, sugar-sweetened beverages, and diet drinks may lower MetS risk in T1DM.

1060-P: Associations of Dietary Patterns and Nutrients with Biomarkers of Inflammation in Adults with and without Type 1 Diabetes

Background: People with type 1 diabetes (T1D) have a greater risk of developing cardiovascular diseases than people without diabetes. Inflammation plays a key role in atherosclerosis and diet has been known to modify inflammation. However, little is known about this association in T1D. Methods: We conducted a six-year longitudinal analysis of data from Coronary Artery Calcification in Type 1 Diabetes study [n=1255; T1D: n=563; non-DM: n=692] collected at baseline, year 3 and year 6. Participants completed a validated food frequency questionnaire, a physical examination, and fasting (12h overnight fast) biochemical analyses. Biomarkers of inflammation and atherosclerosis [C-reactive protein (CRP), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), homocysteine (hcy) and adiponectin] were determined in serum samples at three time points. Dietary patterns were identified using factor analysis. Generalized estimating equations were used to examine associations of dietary patterns with inflammation in models adjusted for traditional cardiovascular risks. Results: In a multivariate model, increasing intake of carbohydrates and total fats were positively associated with CRP [β (95% CI): 0.013 (0.003, 0.023) and 0.025 (0.011, 0.039), respectively) and fibrinogen (0.007 (0.005, 0.010) and 0.010 (0.006, 0.014), respectively) when adjusted for age, sex, time, total calories, and diabetes status. Dietary fiber revealed an inverse association with CRP [-0.014 (-0.021, -0.007)], PAI-1 [-0.009 (-0.015, -0.003)], and hcy [-0.002 (-0.005, 0.000)], and a positive association with adiponectin [0.005 (0.000, 0.009)]. A dietary pattern characterized by ‘veggies, meats and alcohol’ was positively associated with adiponectin [0.022 (0.001, 0.043)]. Conclusions: Dietary carbohydrates and total fats were associated with biomarkers of inflammation and atherosclerosis, while fiber revealed protective associations in adults with and without T1D. Disclosure A. Basu: None. L. Chien: None. A. C. Alman: None. J. K. Snell-bergeon: Stock/Shareholder; Self; GlaxoSmithKline plc. Funding National Institutes of Health (R01HL61753)

418-P: Adults with T1D, Neuropathy, and Depressive Symptoms Are in Need of Clinical Intervention

Prolonged T1D and suboptimal glycemic control contributes to diabetic peripheral neuropathy, which may occur with impairing psychological symptoms. This study examined the association between neuropathy and depressive symptoms in adults with T1D.Neuropathy was assessed using the Michigan Neuropathy Screening Instrument history and physical assessment (clinical scores >2 indicate neuropathy) in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study. Depressive symptoms were assessed by the Beck Depression Inventory (BDI-II; scores >14 indicate clinically elevations).Neuropathy was detected in 22% of participants with T1D (N=364; 55% female; age=51±9 years; T1D duration=38±9 years) and elevated depressive symptoms in 10%. Participants with neuropathy were older and had longer T1D duration and higher BDI-II scores; they were more likely to have elevated depressive symptoms. In logistic regression models adjusted for age, sex, T1D duration, and A1C, neuropathy was associated with a 7-fold increased odds of elevated depressive symptoms (OR [95% CI] = 7.5 [3.1-17.9, p<0.0001). It is well known that significant pain and depression result in functional impairment across various domains of daily life. Interventions to reduce clinically elevated depressive symptoms and promote adaptive coping in adults with T1D with neuropathy are largely absent, and critically needed.View largeDownload slideView largeDownload slide DisclosureS. E. Wetter: None. K. A. Driscoll: None. J. K. Snell-bergeon: Stock/Shareholder; Self; GlaxoSmithKline plc.FundingNational Institutes of Health (R01HL113029)

Associations of dietary patterns and nutrients with coronary artery calcification and pericardial adiposity in a longitudinal study of adults with and without type 1 diabetes.

To examine the associations of dietary patterns and nutrients with coronary artery calcification (CAC) and pericardial adiposity (PAT) in adults with and without type 1 diabetes. We conducted a six-year longitudinal analysis of data from Coronary Artery Calcification in Type 1 Diabetes study [n = 1255; T1D: n = 563; non-DM: n = 692] collected at baseline, year 3 and year 6. Participants completed a validated food frequency questionnaire, a physical examination, and fasting (12h overnight fast) biochemical analyses. CAC and PAT were measured using electron beam computed tomography. Dietary patterns were identified using factor analysis. Generalized estimating equations were used to examine associations of dietary patterns and nutrients with CAC and PAT in models adjusted for traditional cardiovascular risks. The 'starchy veggies, meats and alcohol pattern' was associated with significantly increased risk of CAC presence in all adjusted models; an increasing trend was observed with CAC progression. Increasing intake of dietary proteins and total fats were also associated with higher risk of the presence and/or progression of CAC in adjusted models (all p < 0.05). PAT was positively associated with dietary total fats, and inversely associated with dietary intakes of saturated fats, omega-3 fats and fiber in models adjusted for age, sex, total calories, time, diabetes status, systolic blood pressure, serum lipids and physical activity. Diets high in total fats and proteins, and in meats (processed and red) and alcohol may increase risks of CAC, while saturated fats, omega-3-fats and fiber may be protective against pericardial adiposity as a risk factor for coronary artery disease. ClinicalTrials.gov Identifier: NCT00005754.