Calcification In Type 1 Diabetes Research Articles

Longitudinal associations of the alternative healthy eating index with coronary artery calcification and pericardial adiposity in US adults with and without type 1 diabetes

Background and aimLong-term associations between the alternative healthy eating index (AHEI) score and two predictive indicators for CVD, pericardial adipose tissue (PAT) and coronary artery calcification (CAC) volume, are lacking. Our study aims to investigate the longitudinal associations of the AHEI score with measures of CAC and PAT in adults with and without type 1 diabetes (T1D). Methods and resultsThe prospective Coronary Artery Calcification in T1D (CACTI) study included 652 people with T1D and 764 people without diabetes (non-DM) (19–56 years old) and was conducted in 2000–2002, 2003–2004, and 2006–2007. At each visit, food frequency questionnaires were collected and PAT and CAC were measured using electron beam computed tomography. Two variables were used for CAC analyses: a continuous variable for the square-root tranformed volume (SRV) for each visit and a second variable identified CAC progression from baseline to visit 3. Mixed effect models and a logistic regression model were used to conduct statistical analyses. A one-point increase in the AHEI score was significantly associated with a −0.12 cm3 (95% CI: −0.17, −0.08; p-value<0.0001) decrease in PAT volume in combined analyses, a −0.16 cm3 (95% CI: −0.22, −0.09; p-value<0.0001) decrease in the non-DM group, a marginally significant −0.07 cm3 (95% CI: −0.14, 0.002; p-value = 0.0571) decrease in the T1D group, and was not associated with either CAC outcome. ConclusionThe AHEI score is inversely associated with PAT; the association revealed greater magnitude of PAT reduction in the non-DM group. The AHEI score did not associate with CAC progression.

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.

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)

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

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.

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 Glycated Hemoglobin in Participants with and without Type 1 Diabetes.

Background: Diet has been associated with poor glycemic control in diabetes. Few studies have examined this association in people with type 1 diabetes (T1D), who are at a higher risk for cardiovascular disease than people without diabetes. Methods: We report data from cross-sectional and longitudinal analyses from a coronary artery calcification in type 1 diabetes (CACTI) study (n = 1257; T1D: n = 568; non-diabetic controls: n = 689) collected between the years 2000 and 2002. Participants completed a validated food frequency questionnaire, a physical examination, and biochemical analyses. Dietary patterns based on variations in food group intake were created with principal components analysis. Linear regression was used to examine the associations of dietary patterns, macronutrients, and food groups with HbA1c in a model adjusted for relevant covariates and stratified by diabetes status. Results: Three dietary patterns were identified: “fruits, veggies, meats, cereal”, “baked desserts” and “convenience foods and alcohol” patterns. At baseline, a higher intake of the “baked dessert” pattern was significantly associated with higher HbA1c in T1D at baseline as well at year 6 of the study when adjusted for age, sex, BMI, total calories, and diabetes duration. No such associations were observed in the case of non-diabetic controls. Dietary saturated fats and animal fats were also positively associated with HbA1c in adults with T1D at baseline and/or at year 6. Conclusions: The habitual intake of a dietary pattern that is characterized by an increased intake of added sugar and saturated fats, such as in baked desserts, may increase risks of poor glycemic control in T1D.

1542-P: Associations of Dietary Patterns with Glycemia in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study

Background: Among the modifiable risk factors, diet plays an important role in the risks and progression of poor glycemic control in diabetes. However, few studies have examined this association in people who have type 1 diabetes (T1D), who are at a greater risk of developing cardiovascular diseases than people without diabetes. Methods: We conducted cross-sectional and longitudinal analyses of data from CACTI study [n=1257; T1D: n=568; nondiabetic controls: n=689] collected between March 2000 and April 2002. Participants completed a validated food frequency questionnaire, a physical examination and fasting biochemical analyses (12h fast). At baseline, dietary patterns based on variations in food group intake were created with principal components analysis (PCA). Linear regression was used to examine associations of dietary patterns with HbA1c in a model adjusted for age and sex and stratified by diabetes status. Results: Three dietary patterns were identified using PCA as follows: ’fruits, veggies, meats, cereal’, ’baked desserts’ and ’convenience foods and alcohol’ patterns. At baseline, higher intake of ’baked dessert’ pattern was significantly associated with higher HbA1c in T1D (β±SE: 0.10±0.05, p=0.03), but not in nondiabetic controls (0.06±0.04, p=0.21) when adjusted for age, sex and baseline total calories, as well as diabetes duration for T1D. At year-6, baseline higher intake of ’baked dessert’ pattern tended to be associated with increasing HbA1c in T1D (β±SE: 0.11±0.06, p=0.06), but not in nondiabetic controls (0.01±0.04, p=0.68) when adjusted for the same covariates. Conclusions: Habitual intake of a dietary pattern that is characterized by an increased intake of added sugar and saturated fats, such as in baked desserts may increase risks of poor glycemic control in T1D. Disclosure A. Basu: None. A.C. Alman: None. J.K. Snell-Bergeon: Stock/Shareholder; Self; GlaxoSmithKline plc. Funding American Diabetes Association (7-13-CD-10 to J.K.S-B.)

Abstract P128: Periodontal Disease and Coronary Artery Calcium in Adults With Type 1 Diabetes

Introduction: Adults with type 1 diabetes (T1D) have at least a two-fold risk of developing coronary artery disease (CAD) compared to adults without diabetes (Non-DM); Periodontal disease is also increased in T1D, due at least in part to hyperglycemia. There is increasing recognition that periodontal disease is linked to CAD through systemic inflammation, which may be a mechanism through which diabetes increases CAD. In this study, we examined the association between self-reported gum disease and coronary artery calcium (CAC) in the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) cohort. Methods: There were 1416 adults (652 with T1D, 764 Non-DM, mean±SD age 37±8years, 48% men) enrolled in the CACTI cohort in 2000. The cohort completed four visits between 2000 and 2018: at baseline and after 3, 6 and 14 years of follow-up. At each visit, participants self-reported gum disease diagnosis. CAC volume was measured by computed tomography at each visit and was square root transformed for analysis. Linear mixed effects models were used to examine the association between self-reported gum disease and change in CAC volume. Results: At baseline, 12% of Non-DM and 16% of T1D participants (p=0.054) reported having gum disease. The prevalence of gum disease increased across visits to 18% in participants with T1D vs. 13% in Non-DM participants at visit 2 (p=0.01); 22% in participants with T1D at visit 3 vs. 14% in Non-DM participants (p=0.0009) and 25% in participants with T1D vs. 17% in Non-DM participants at visit 4 (p=0.023). Self-reported gum disease was associated with a significantly greater increase in CAC volume over time (Table, p&lt;0.0001) among people with T1D, but not in people without diabetes (p=0.13) when adjusted for age, sex, body mass index, LDL cholesterol and smoking (p-value for diabetes x gum disease interaction &lt;0.0001). Conclusion: Periodontal disease prevalence was increased in adults with T1D, and was independently associated with increase in CAC volume over 14 years of follow-up in this population.

Increased apolipoprotein C3 drives cardiovascular risk in type 1 diabetes.

Type 1 diabetes mellitus (T1DM) increases the risk of atherosclerotic cardiovascular disease (CVD) in humans by poorly understood mechanisms. Using mouse models of T1DM-accelerated atherosclerosis, we found that relative insulin deficiency rather than hyperglycemia elevated levels of apolipoprotein C3 (APOC3), an apolipoprotein that prevents clearance of triglyceride-rich lipoproteins (TRLs) and their remnants. We then showed that serum APOC3 levels predict incident CVD events in subjects with T1DM in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. To explore underlying mechanisms, we investigated the impact of Apoc3 antisense oligonucleotides (ASOs) on lipoprotein metabolism and atherosclerosis in a mouse model of T1DM. Apoc3 ASO treatment abolished the increased hepatic Apoc3 expression in diabetic mice - resulting in lower levels of TRLs - without improving glycemic control. APOC3 suppression also prevented arterial accumulation of APOC3-containing lipoprotein particles, macrophage foam cell formation, and the accelerated atherosclerosis in diabetic mice. Our observations demonstrate that relative insulin deficiency increases APOC3 and that this results in elevated levels of TRLs and accelerated atherosclerosis in a mouse model of T1DM. Because serum levels of APOC3 predicted incident CVD events in the CACTI study, inhibiting APOC3 might reduce CVD risk in T1DM patients.

1584-P: Associations of Dietary Patterns with Atherosclerosis in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study

Background: Among the modifiable risk factors, diet plays an important role in the risks and progression of atherosclerotic cardiovascular disease (ASCVD). However, few studies have examined this association in people with type 1 diabetes (T1D) who are at a greater risk of developing ASCVD than nondiabetic (non-DM) controls. Methods: We conducted cross-sectional and longitudinal analyses of data from CACTI study [n=1257; T1D: n=568; non-DM: n=689] collected between March 2000 and April 2002. Participants completed a validated food frequency questionnaire, a physical examination and fasting biochemical analyses (12h fast), and coronary artery calcification (CAC) was measured using electron beam computed tomography. At baseline, dietary patterns based on variations in food group intake were created with principal components analysis (PCA). Logistic regression was used to examine associations of dietary patterns with the CAC prevalence in a model adjusted for age and sex and stratified by diabetes status. Results: Three dietary patterns were identified using PCA as follows: ‘fruits, veggies, meats, cereal’, ‘baked desserts’ and ‘convenience foods and alcohol’ patterns. At baseline, no significant associations of dietary patterns with CAC prevalence were observed. At year-6, ‘baked dessert’ pattern was significantly associated with increased risk of CAC (&amp;lt;0 vs. 0) in T1D [odds ratios (OR) and 95% CI: 2.05 (1.19, 3.51)], but not in non-DM [0.74 (0.51, 1.06)] when adjusted for age, sex and baseline total calories, as well as duration of diabetes for T1D. Conclusions: Habitual intake of a dietary pattern that is characterized by an increased intake of added sugar and fats, such as in baked desserts may increase risks of atherosclerosis in T1D. Thus, dietary adjustments to improve this pattern may be atheroprotective. Disclosure A. Basu: None. A.C. Alman: None. J.K. Snell-Bergeon: None. Funding American Diabetes Association (7-13-CD-10 to J.K.S-B.)

407-P: Growth Differentiation Factor 15, Coronary Atherosclerosis and Diabetic Kidney Disease in Adults with Type 1 Diabetes (T1D)

Objective: In health, circulating growth differentiation factor (GDF)-15 is low, and concentrations are thought to increase rapidly in response to cardiac and renal injuries. GDF-15 is secreted in response to inflammation, oxidative stress and hypoxia, and therefore may be a biomarker of subclinical vascular disease. Yet, the relationships between GDF-15, coronary artery disease and diabetic kidney disease (DKD) remain incompletely understood. Accordingly, the objective of this study was to delineate these relationships in adults with T1D. Methods: Participants with (n=377, HbA1c 7.8±1.3%, duration 37.1±8.6 years) and without T1D (n=456) in the Coronary Artery Calcification in type 1 diabetes (CACTI) study were assessed for serum GDF-15, coronary artery calcification (CAC) measured using 128-slice spiral CT, urinary albumin-to-creatinine ratio (UACR) and eGFR calculated by CKD-EPI creatinine. Impaired GFR was defined as eGFR &amp;lt;60mL/minutes/1.73m2, albuminuria as UACR ≥30 mg/g, high and very high CAC score as ≥100 and ≥300 AU. Multivariable (age, sex, HbA1c, and antihypertensive medication use) logistic models were applied to examine the relationships. Results: Participants with T1D had greater GDF-15 concentrations than nondiabetics (666.4 [95% CI 633.9-700.5] vs. 579.1 [558.7-600.4] ng/l, p&amp;lt;0.0001). In participants with type 1 diabetes, higher GDF-15 was associated with greater odds of impaired GFR (OR: 4.40, 95% CI 2.51-7.73, p&amp;lt;0.0001), albuminuria (2.47, 1.60-3.80, p&amp;lt;0.0001), high CAC (1.67, 1.16-2.41, p=0.006) and very high CAC (1.62, 1.01-2.58, p=0.04) in multivariable models (per 1 SD increase in natural log GDF-15). Conclusion: In this cross-sectional analysis, GDF-15 was strongly associated with DKD and coronary atherosclerosis in adults with T1D, independent of glycemic control. As a biomarker, GDF-15 holds promise to aid in risk stratification and clinical trial enrichment. Disclosure P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. R.M. Sippl: None. M. Rewers: None. J.K. Snell-Bergeon: None. Funding National Institutes of Health; JDRF

Dietary fiber intake and glycemic control: coronary artery calcification in type 1 diabetes (CACTI) study

BackgroundDietary fiber has been recommended for glucose control, and typically low intakes are observed in the general population. The role of fiber in glycemic control in reported literature is inconsistent and few reports are available in populations with type 1 diabetes (T1D).MethodsUsing data from the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study [n = 1257; T1D: n = 568; non-diabetic controls: n = 689] collected between March 2000 and April 2002, we examined cross-sectional (baseline) and longitudinal (six-year follow-up in 2006–2008) associations of dietary fiber and HbA1c. Participants completed a validated food frequency questionnaire, and a physical examination and fasting biochemical analyses (12 h fast) at baseline visit and at the year 6 visit. We used a linear regression model stratified by diabetes status, and adjusted for age, sex and total calories, and diabetes duration in the T1D group. We also examined correlations of dietary fiber with HbA1c.ResultsBaseline dietary fiber intake and serum HbA1c in the T1D group were 16 g [median (IQ): 11–22 g) and 7.9 ± 1.3% mean (SD), respectively, and in the non-diabetic controls were 15 g [median (IQ): 11–21 g) and 5.4 ± 0.4%, respectively. Pearson partial correlation coefficients revealed a significant but weak inverse association of total dietary fiber with HbA1c when adjusted for age, sex, diabetes status and total calories (r = − 0.07, p = 0.01). In the adjusted linear regression model at baseline, total dietary fiber revealed a significant inverse association with HbA1c in the T1D group [β ± SE = − 0.32 ± 0.15, p = 0.034], as well as in the non-diabetic controls [− 0.10 ± 0.04, p = 0.009]. However, these results were attenuated after adjustment for dietary carbohydrates, fats and proteins, or for cholesterol and triglycerides. No such significance was observed at the year 6 follow-up, and with the HbA1c changes over 6 years.ConclusionThus, at observed levels of intake, total dietary fiber reveals modest inverse associations with poor glycemic control. Future studies must further investigate the role of overall dietary quality adjusting for fiber-rich foods in T1D management.

Serum Uromodulin Predicts Less Coronary Artery Calcification and Diabetic Kidney Disease Over 12 Years in Adults With Type 1 Diabetes: The CACTI Study.

Novel biomarkers are needed to better predict coronary artery calcification (CAC), a marker of subclinical atherosclerosis, and diabetic kidney disease (DKD) in type 1 diabetes. We evaluated the associations between serum uromodulin (SUMOD [a biomarker associated with anti-inflammatory and renal protective properties]), CAC progression, and DKD development over 12 years. Participants (n = 527, 53% females) in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study were examined during 2002-2004, at a mean age of 39.6 ± 9.0 years and a median duration of diabetes of 24.8 years. Urine albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) determined by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation were measured at baseline and after a mean follow-up period of 12.1 ± 1.5 years. Elevated albumin excretion was defined as ACR ≥30 mg/g, rapid GFR decline (>3 mL/min/1.73 m2/year), and impaired GFR as eGFR <60 mL/min/1.73 m2. SUMOD was measured on stored baseline plasma samples (Meso Scale Discovery). CAC was measured using electron beam computed tomography. CAC progression was defined as a change in the square root-transformed CAC volume of ≥2.5. Higher baseline SUMOD level conferred lower odds of CAC progression (odds ratio 0.68; 95% CI 0.48-0.97), incident elevated albumin excretion (0.37; 0.16-0.86), rapid GFR decline (0.56; 0.35-0.91), and impaired GFR (0.44; 0.24-0.83) per 1 SD increase in SUMOD (68.44 ng/mL) after adjustment for baseline age, sex, systolic blood pressure, LDL cholesterol, and albuminuria/GFR. The addition of SUMOD to models with traditional risk factors also significantly improved the prediction performance for CAC progression and incident DKD. Higher baseline SUMOD level predicted lower odds of both CAC progression and incident DKD over 12 years in adults with type 1 diabetes.