Brachial Artery Distensibility Research Articles

Longitudinal study of birthweight, blood pressure, and markers of arterial stiffness in children age six among the TIDES cohort.

Although some studies have observed an association between birthweight and cardiovascular disease in adulthood, fewer have investigated whether birthweight is linked to cardiovascular health in early childhood. This study assesses the association between birthweight and cardiovascular outcomes in children 6 years of age. Birthweight, blood pressure (BP), and markers of arterial stiffness in children, including brachial artery distensibility and carotid-femoral pulse wave velocity (cfPWV), were obtained from 324 participants in The Infant Development and the Environment Study, a prospective multisite pregnancy cohort. Birthweight was converted into sex-specific birthweight-for-gestational-age (bw/ga) z -scores based on the INTERGROWTH-21st standard. Following 2017 American Academy of Pediatrics guidelines, SBP and DBP were transformed into sex, age, and height-specific z -scores. Associations between birthweight and cardiovascular outcomes were assessed using nested multivariable linear regression models among the overall and sex-stratified samples. Among the overall sample, bw/ga z -score was positively associated with cfPWV [b = 0.11 m/s, 95% confidence interval (CI): 0.01 m/s, 0.21 m/s] in crude and adjusted models. No associations between birthweight and cardiovascular outcomes were detected among the sex-stratified analyses. Overall, birthweight was not related to cardiovascular outcomes in children 6 years old. However, infants born with a higher birthweight may be at risk for higher cfPWV in childhood. Early intervention in pregnant people at risk of delivering high birthweight infants may be warranted if results are replicated.

Long-term exposure to ambient air pollution and measures of central hemodynamics and arterial stiffness among multiethnic Chicago residents

ObjectivesTo examine whether long-term air pollution exposure is associated with central hemodynamic and brachial artery stiffness parameters.MethodsWe assessed central hemodynamic parameters including central blood pressure, cardiac parameters, systemic vascular compliance and resistance, and brachial artery stiffness measures [including brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR)] using waveform analysis of the arterial pressure signals obtained from a standard cuff sphygmomanometer (DynaPulse2000A, San Diego, CA). The long-term exposures to particles with an aerodynamic diameter < 2.5 μm (PM2.5) and nitrogen dioxide (NO2) for the 3-year periods prior to enrollment were estimated at residential addresses using fine-scale intra-urban spatiotemporal models. Linear mixed models adjusted for potential confounders were used to examine associations between air pollution exposures and health outcomes.ResultsThe cross-sectional study included 2,387 Chicago residents (76% African Americans) enrolled in the ChicagO Multiethnic Prevention And Surveillance Study (COMPASS) during 2013–2018 with validated address information, PM2.5 or NO2, key covariates, and hemodynamics measurements. We observed long-term concentrations of PM2.5 and NO2 to be positively associated with central systolic, pulse pressure and BAR, and negatively associated with BAD, and BAC after adjusting for relevant covariates. A 1-µg/m3 increment in preceding 3-year exposures to PM2.5 was associated with 1.8 mmHg higher central systolic (95% CI: 0.98, 4.16), 1.0 mmHg higher central pulse pressure (95% CI: 0.42, 2.87), a 0.56%mmHg lower BAD (95% CI: -0.81, -0.30), and a 0.009 mL/mmHg lower BAC (95% CI: -0.01, -0.01).ConclusionThis population-based study provides evidence that long-term exposures to PM2.5 and NO2 is related to central BP and arterial stiffness parameters, especially among African Americans.

1233-P: The Association between Subgingival Microbiome, Subclinical Cardiovascular Disease, and Type 1 Diabetes

Background: Dysbiosis in the subgingival microbiome is the root cause of periodontal disease, a risk factor of cardiovascular disease (CVD), but its association with subclinical CVD, particularly among those with type 1 diabetes (T1D) is unclear. Methods: We included 283 subjects with (n=141) and without (n=142) T1D. We performed 16S rDNA sequencing on subgingival plaque samples and identified amplicon sequence variants. Subclinical CVD was measured by carotid intima-media thickness (cIMT), pulse wave velocity (PWV), and brachial artery distensibility (BrachD). Results: Beta diversity differed between T1D and the nondiabetes (ND) group (F = 1.66, P=0.024). As shown in Figure 1, in the stratified generalized linear model (adjusted for age, gender, race, smoking, alcohol drinking, BMI, and additionally HbA1c in the T1D model), we observed 4 taxa in the T1D group and 28 taxa in the ND group to be associated with cIMT (all Padj&amp;lt; 0.05). Moreover, 8 and 17 taxa were associated with BrachD (lower value suggests worse status) in T1D and ND groups, and 6 and 5 for PWV (all Padj &amp;lt; 0.05). Some associations were in opposite directions by diabetes status, especially for cIMT. Conclusion: We observed differences in the subgingival microbiome profile between those with and without T1D. Subgingival microbiome taxa were associated with subclinical CVD measures, with some differences observed by diabetes status. Disclosure M. Xiao: None. A. Sarkar: None. J.K. Snell-Bergeon: None. S. Chandrasekaran: None. L.R. Johnson: None. B.R. Burkhardt: None. J. Petrosino: None. A.C. Alman: None. Funding National Institutes of Health (5R01DE026480)

1311-P: Insulin Resistance in Non-obese Young Adults with Type 1 Diabetes

Insulin resistance has been noted in youth and adults with type 1 diabetes (T1D) and is associated with higher levels of cardiovascular and kidney complications. Obesity is increasing in populations with T1D, and the degree of insulin resistance in younger adults with T1D who are free from complications and non-obese isn’t clear. We performed hyperinsulinemic euglycemic clamps in non-obese adults aged 20-45 with and without T1D. Inclusion criteria included diabetes duration &amp;gt; 5 years and HbA1c &amp;lt;9% among people with T1D, or no diabetes based on fasting glucose and HbA1c among controls; Body mass index (BMI) &amp;lt; 30 kg/m2, no use of statins or other medication affecting insulin sensitivity, non-smokers and normal thyroid function. Participants were given a fixed macronutrients study diet for 2 days and were asked to refrain from vigorous exercise for 72 hours. Clamps were performed by a single investigator after an overnight stay. A sliding scale insulin infusion was used overnight for participants with T1D. Arterial stiffness (brachial artery distensibility, pulse wave velocity and reactive hyperemia index) was assessed. There were 47 participants, 24 with T1D and 23 without diabetes. 53% were women (25/47), and the average age did not differ between controls and people with T1D (31 ± 6 years vs. 28 ± 6 years, p=0.12). Whole body insulin sensitivity estimated by glucose infusion rate (GIR) per kg fat free mass was reduced by more than half in adults with T1D (LS mean ± SE =5.4 ± 1.0 mg/kg FFM/min) compared to adults without diabetes (12.7 ± 1.0 mg/kg FFM/min, p&amp;lt;0.0001). In contrast, there were no differences in BMI, body fat, urinary albumin, or measures of arterial stiffness by diabetes status. Young, non-obese adults with T1D are profoundly insulin resistant compared to nondiabetic adults, even when no differences in vascular stiffness or kidney complications are apparent. These results suggest that insulin resistance may occur earlier than vascular or kidney complications in people with T1D and is independent of obesity. Disclosure C.J. Chartier-Logan: None. I.E. Schauer: None. M. Cree-Green: Consultant; Pollie Inc. Research Support; Amino Corp LLC. L. Pyle: None. B.C. Bergman: Research Support; Eli Lilly and Company. J.K. Snell-Bergeon: None. Funding JDRF (2-SRA-2019-849-S-B)

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.

Determinants of arterial elastic function in middle-aged and elderly people: A population-based cross-sectional study from a low-income population in China.

Arterial stiffness is closely associated with the occurrence of many cardiovascular and cerebrovascular diseases. However, the risk factors and mechanisms related to arterial stiffness development have only been partially elucidated. We aimed to describe arterial elastic function and its influencing factors in middle-aged and elderly people in rural China. This was a cross-sectional study conducted among residents, aged ≥45 years, of Tianjin, China, between April and July 2015. Data regarding participant demographics, medical history, lifestyle, and physical examination results were collected and assessed the association with arterial elastic function using linear regression. Of the 3,519 participants, 1,457 were male (41.4%). Brachial artery distensibility (BAD) decreased by 0.5%/mmHg with every 10-year increment in age. The mean BAD value was 0.864%/mmHg lower in women than in men. With each unit increase in mean arterial pressure, the BAD decreased by 0.042%/mmHg. In patients with hypertension or diabetes, the BAD decreased by 0.726 and 0.183%/mmHg, respectively, compared with those without hypertension or diabetes. For each unit increase in triglyceride (TG) level, the mean BAD increased by 0.043%/mmHg. With each increase in body mass index (BMI) category, the BAD increased by 0.113%/mmHg. Brachial artery compliance (BAC) decreased by 0.007 ml/mmHg with each 10-year increase in age, and brachial artery resistance (BAR) increased by 30.237 dyn s-1 cm-5. The mean BAC in women was 0.036 ml/mmHg lower and the mean BAR was 155.231 dyn s-1 cm-5 higher in women than in men. In individuals with hypertension, the mean BAC decreased by 0.009 ml/mmHg and the mean BAR increased by 26.169 dyn s-1 cm-5. With each increase in BMI category, the mean BAC increased by 0.005 ml/mmHg and the mean BAR decreased by 31.345 dyn s-1 cm-5. For each unit increase in TG level, the mean BAC increased by 0.001 ml/mmHg. These findings indicate that age, sex, mean arterial pressure, BMI, diabetes, hypertension, and TG level are independently associated with the components of peripheral arterial elasticity. Understanding the factors influencing arterial stiffness is important for developing interventions to minimize arterial aging and cardiovascular and cerebrovascular diseases caused by arterial aging.

Acute Effects of 160-Degree V-Shape Whole-Body Periodic Acceleration (WBPA) on Blood Pressure and Cardiovascular Hemodynamics

Whole-Body Periodic Acceleration (WBPA) has been reported to induce endothelial nitric oxide and cause vasodilation. However, the effects of WBPA on blood pressure and cardiovascular hemodynamics are still unclear and controversial. The objective of this study was to determine whether a single session of 160-degree V-shape Whole-Body Periodic Acceleration (WBPA-V-160), i.e., periodic motion of the supine body headward to footward, improved blood pressure and cardiovascular parameters. A pre-evaluation and post-evaluation of blood pressure and cardiovascular hemodynamics via DynaPulse Noninvasive and Quantitative Hemodynamic Profile Analysis were performed after a single 30 min trial of WBPA-V-160 with a moving distance, headward to footward, of 2 mm, at a constant frequency of 4 Hz. Systolic BP, diastolic BP, heart rate, end systolic pressure, end diastolic pressure, mean arterial BP, and pulse pressure at post-evaluation were significantly lower than at pre-evaluation after WBPA-V-160, whereas systemic vascular compliance and brachial artery distensibility at post-evaluation were significantly higher than at pre-evaluation. The WBPA-V-160, performed for 30 min, did improve blood pressure and cardiovascular hemodynamics by lowing the BP parameters and enhancing systemic vascular compliance.

1093-P: Vascular Health across the Lifespan in Women with and without Type 1 Diabetes (TID)

Introduction: Cardiovascular disease (CVD) is the leading cause of death in people with T1D, and women with T1D are disproportionately affected. However, few studies have examined how T1D affects vascular health in women across the lifespan. Methods: Women ages 18-79 with (N=309) and without T1D (n=351) were examined cross-sectionally for markers of CVD: pulse wave velocity (PWV) , augmentation index (AiX) , pulse height (PH) , brachial artery distensibility (BrachD) , subendocardial viability index (SVI) , and carotid intima thickness (cIMT) . Menopausal status was self-reported. Body composition was measured by Dual Xray Absorptiometry. CVD markers were examined by diabetes status and age using linear regression models adjusted for menopausal status. Results: Age did not differ in women with and without diabetes (49 ± 12 vs. 50±14 years, p=0.32) . Women with T1D had higher systolic blood pressure (SBP) , cIMT, PWV and PH, and lower BrachD and SVI than non-diabetic women (Table 1) . Changes in blood pressure, cIMT, AiX, and SVI with age differed by diabetes status, as demonstrated by a significant interaction. While SBP and Aix were increased more in women with T1D at younger ages, cIMT and SVI worsened with age to a greater extent in T1D. Conclusions: Women with T1D have worse CVD markers than women without diabetes across the lifespan, with more arterial stiffness at younger ages and more atherosclerosis and lower SVI later in life. Disclosure C.J.Chartier-logan: None. A.C.Alman: None. V.Shah: Advisory Panel; Medscape, Sanofi, Consultant; Dexcom, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc.

439-P: Disparate Effects of Menopause on Cardiovascular Risk in Women with Type 1 Diabetes

Introduction: Women with type 1 diabetes (T1D) are at increased risk for cardiovascular disease (CVD) , and menopause increases CVD risk. However, little is known about menopause and CVD risk in T1D. Methods: Women with (N=64) and without T1D (n=63) ages 47-55 years were examined for CVD risk factors and surrogate CVD markers: pulse wave velocity (PWV) , augmentation pressure (AP) and pulse height (PH) , brachial artery distensibility (BrachD) , and subendocardial viability index (SVI) . Body composition was measured by Dual Xray Absorptiometry. Menopausal status was determined by self-report. CVD markers were examined by diabetes and menopausal status using linear regression models adjusted for age. Results: Mean ± SD age was 51±2.5 years in women with T1D and 51 ± 2.4 years in women without diabetes (p=0.32) . The percentage postmenopausal did not differ (30% vs. 32%, p=0.8) between T1D and nondiabetes women. As shown in the table, women with T1D had higher systolic blood pressure and measures of arterial stiffness (PWV, AP, PH, and BrachD) and lower SVI than women without diabetes. Menopause was associated with a greater loss in fat free mass and a greater increase in PWV and AP among women with T1D compared to women without diabetes. Conclusions: Women with T1D have worse CVD markers, and menopause is associated with greater increases in arterial stiffness and loss in lean body mass than in nondiabetes women, independent of age. Disclosure H.K.Wise: None. E.Malecha: None. C.J.Chartier-logan: None. L.Pyle: None. A.Keshawarz: None. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc. Funding American Diabetes Association (7-13-CD-10)

36-OR: Bromocriptine Quick Release (BCQR) Improves Vascular Health in Youth with Type 1 Diabetes Even if Normal Weight

Background: Global vascular dysfunction is well-recognized in youth with type 1 diabetes (T1D) , accentuating lifetime cardiovascular event risk and making therapeutic strategies to mitigate vascular dysfunction a high priority. In the BCQR-T1D study, we tested the hypothesis that BCQR, a medication used in obese adults with type 2 diabetes, would improve vascular health in T1D youth. Methods: BCQR-T1D was a placebo-controlled, random-order, double-blinded, cross-over study investigating cardiovascular and metabolic impacts of BCQR in T1D. Youth were randomized 1:1 to phase-1: 4-weeks of BCQR or placebo after which blood pressure (BP) , peripheral vascular stiffness by brachial artery distensibility (BrachD) , and central aortic stiffness by pulse wave velocity (PWV) , relative area change (RAC) and distensibility from phase-contrast MRI, were performed. Following a 4-week washout period, phase 2 was performed in identical fashion with the alternate treatment. Results: Forty-two adolescents (mean age 15.9 years, HbA1c 8.6%, BMI %ile 71.4, T1D duration 5.8 years) with T1D were enrolled. Compared to placebo, BCQR therapy decreased systolic (∆ = -5 mmHg, p&amp;lt;0.001) and diastolic BP (∆ = -2 mmHg, p=0.039) . BCQR reduced ascending aortic (AA) PWV (∆ = -0.4 m/s, p=0.005) , and increased RAC (∆ = -2.6%, p=0.022) and distensibility (∆ = 0.%/mmHg, p=0.010) . In the thoraco-abdominal aorta, BCQR decreased PWV (∆ = -0.2 m/s, p=0.013) and increased distensibility (∆ = 0.%/mmHg, p=0.032) . Of interest, in the normal-weight participants, BCQR improved systolic BP (∆ = -5 [95.0%CI: -7, -1] mmHg, p= 0.009) , AA PWV (∆ = -0.4 [95.0%CI: -0.7, 0] m/s, p= 0.030) and BrachD (∆ = 0.56 %/mmHg, p=0.023) , and tended to improve AA distensibility (∆ = 0.[95.0%CI: -0.01, 0.19] %/mmHg, p= 0.084) . Conclusions: BCQR improved BP, central and peripheral aortic stiffness and pressure hemodynamics in T1D adolescents over 4 weeks vs. placebo, even if normal weight, supporting future longer-term studies. Disclosure M.Schäfer: None. I.E.Schauer: None. K.J.Nadeau: None. L.Browne: None. U.Truong: None. P.Bjornstad: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Horizon Therapeutics plc, LG Chem, Lilly, Novo Nordisk, Consultant; AstraZeneca, Bristol-Myers Squibb Company. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc. A.Baumgartner: None. K.S.Hunter: None. J.Reusch: Advisory Panel; Medtronic. A.J.Barker: None. Funding JDRF BROM QR THERP3-SRA-2015-125-M-R

0599 Sleep duration across the lifespan in type 1 diabetes and association with cardiometabolic risk

Abstract Introduction Individuals with type 1 diabetes (T1D) are at high risk for morbidity and mortality from cardiovascular disease which begins as early as adolescence. Some studies have reported a high prevalence of insufficient sleep in this population which may be due to behavioral and physiological aspects of T1D and its management. Emerging evidence suggests a link between short sleep duration and increased cardiometabolic risk, but this has not been specifically examined across the lifespan in individuals with T1D. Methods Inclusion criteria were T1D duration &amp;gt; 9 months, HbA1c 6.5-10% for adults and ≤ 12% for adolescents, and ages 12-60 years. Participants completed home monitoring for one week with continuous glucose monitoring (CGM) and wrist actigraphy prior to a study visit with anthropometric measurements, fasting autonomic/orthostatic and laboratory testing. Peripheral arterial stiffness was measured by Dynapulse brachial artery distensibility (BAD), and insulin sensitivity was estimated by the validated CACTI equation utilizing waist circumference, fasting triglycerides, adiponectin, and diastolic blood pressure. Sleep variables, glycemic markers and health parameters were examined by age group (adolescent vs. adult) using students t-test for univariate comparisons, and linear regression models for age, sex and diabetes duration-adjusted comparisons by age group. Results Forty-two adolescents (mean age 16 ± 3 years, diabetes duration 7.4 ± 5 years, HbA1c 8.4 ± 1.1%) and 42 adults (mean age 41 ± 10 years, diabetes duration 21 ± 13 years, HbA1c 7.4 ± 0.9%) completed the study. Sixty-two percent of adolescents and 74% of adults obtained insufficient sleep (&amp;lt; 7 hours of sleep per night). When examined in linear regression adjusted for age group, sex, diabetes duration and age, insufficient sleep was associated with higher BMI (adults), BMI percentile (adolescents), waist circumference, systolic blood pressure, and lower estimated insulin sensitivity and BAD (all p &amp;lt; 0.05). Conclusion Most adolescents and adults with T1D obtained insufficient sleep. Objectively-estimated insufficient sleep was associated with worse markers of cardiometabolic risk. Further study examining the impact of sleep health interventions in this population is warranted as sleep may be an important and novel target for improving cardiometabolic health in individuals with T1D. Support (If Any) JDRF grant 3-SRA-2015-125-M-R

Abstract P162: Cardiovascular Disease And Periodontal Disease In Type 1 Diabetes

Type 1 diabetes (T1D) is a condition in which the body’s immune system destroys insulin-producing beta cells, resulting in hyperglycemia. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in those with T1D. Periodontal disease (PD) is the 6th major complication of T1D. Oral bacteria have been detected in atherosclerotic plaques. Thus, oral bacteria may play a causal role in cardiovascular disease. The aims of this study are to determine how subclinical measures of cardiovascular disease differ by diabetes status and how they are related to the extent of periodontal disease. It is hypothesized that people with T1D will have stiffer vessels with higher pulse wave velocity (PWV), lower brachial artery distensibility (BrachD), and higher carotid intima-media thickness (cIMT) compared to non-diabetic controls. It is also hypothesized that people with T1D will have a higher prevalence of PD compared to non-diabetic controls. Study visits were performed to assess cardiovascular and periodontal outcomes in people with T1D (n=144) and non-diabetic controls (n=147). Univariate analysis was performed using t-test and chi-square to test for significant differences in vascular measures and periodontal status between T1D and controls. Age and sex-adjusted multivariate linear and logistic regression was used to further examine differences in vascular measures and periodontal disease by diabetes status. PWV was significantly higher in people with T1D compared to controls (8.390 +/- 0.111 vs. 7.822 +/- 0.108, p=0.0003). BrachD was significantly lower in people with T1D compared to controls (5.795 +/- 0.095 vs. 6.413 +/- 0.094, p&lt;0.0001). cIMT was significantly higher in people with T1D compared to controls (0.679 +/- 0.009 vs. 0.626 +/- 0.009, p&lt;0.0001). Adults with T1D were significantly more likely to have moderate to severe PD compared to controls (OR = 2.759, 95% CI [1.310-5.811], p=0.0076). Adults with T1D have worse cardiovascular health as measured by stiffer central vessels, more subclinical atherosclerosis, and lower peripheral vessel distensibility. Adults with T1D had almost 3-fold higher risk of moderate to severe PD compared to non-diabetic adults. The relationship between PD and the increased CVD risk in people with T1D warrants further examination.

Increased Arterial Stiffness Is Associated With Reduced Diastolic Function in Youth With Obesity and Type 2 Diabetes.

Background: Increased arterial stiffness is associated with diastolic dysfunction in adults. Data in youth are lacking, so we examined the impact of arterial stiffness on diastolic function in youth.Methods: We obtained diastolic function and augmentation index, pulse wave velocity, brachial artery distensibility, and carotid stiffness on 612 youth [10–24 years, 65% female, 38% normal weight, 36% obese, and 26% with type 2 diabetes mellitus (T2DM)]. Participants were classified as compliant (C) vs. stiff (S) arteries based on seven arterial stiffness parameters [Global Stiffness Index (GSI), S = GSI > 4). Mean differences in covariates were evaluated by Student's t-tests. A stepwise regression analysis was performed to determine if GSI was an independent predictor of diastolic function.Results: Lower diastolic function and more adverse cardiovascular disease (CVD) risk factors were present in the S group (n = 67) than the C group (n = 545) (p < 0.001). Covariates that were associated with diastolic dysfunction were higher GSI, male sex, higher body mass index (BMI), and systolic blood pressure (SBP) z-score (R2 = 0.18 to 0.25; p ≤ 0.05).Conclusion: Adverse diastolic function is seen in youth with increased arterial stiffness independent of CVD risk factors. Interventions to improve arterial stiffness prior to clinical onset of diastolic dysfunction are needed to prevent development of heart failure.

Cardiorespiratory Fitness, Fat Mass, and Cardiometabolic Health with Endothelial Function, Arterial Elasticity, and Stiffness.

This study aimed to determine whether estimated cardiorespiratory fitness (CRF), fat mass (FM), lean mass (LM), and adiponectin bidirectionally associate with arterial function and structure and if CRF mediates the relationship between cardiometabolic health and arterial outcomes in 9- to 11-yr-old children drawn from the Avon Longitudinal Study of Parents and Children birth cohort, United Kingdom. Brachial artery flow-mediated dilation (FMD), distensibility coefficient (DC), and carotid-radial pulse wave velocity (PWV) were measured by ultrasonography; CRF was measured during the submaximal ergometer test; total FM, trunk FM, and LM were measured by dual-energy x-ray absorptiometry; plasma adiponectin was measured by enzyme assay; and cardiometabolic health was computed based on the International Diabetes Federation criteria for diagnosing metabolic syndrome. We tested bidirectionality by including CRF, FM, LM, and adiponectin as exposures and FMD, DC, and PWV as outcomes, alternatively. Among 5566 participants (2816 (51%) girls; median age, 9.75 yr), CRF per body mass0.21 was directly related to DC (β (95% confidence interval) = 0.004 (<0.0001 to 0.008); P = 0.046), whereas CRF per LM0.54 was inversely associated with PWV (-0.034 (-0.063 to -0.003); 0.032) after adjusting for covariates. These associations remained in bidirectional analyses. Total FM, trunk FM, and LM were bidirectionally and positively associated with FMD and DC. Total FM and trunk FM but not LM had bidirectional and inverse associations with PWV. Adiponectin was not related to FMD, DC, or PWV. CRF partially mediated the associations of cardiometabolic health with FMD (1.5% mediation), DC (12.1% mediation), and PWV (3.5% mediation). Associations of poor cardiometabolic health with adverse arterial structure and function in childhood may be mitigated by increasing CRF. Higher CRF was associated with better arterial structure whereas higher total FM and trunk FM were associated with better arterial function and structure. In the reverse analysis, healthy arterial structure and function were independently associated with increased total FM and trunk FM, suggesting an "arterial paradox."

Impact of Obesity on Measures of Cardiovascular and Kidney Health in Youth With Type 1 Diabetes as Compared With Youth With Type 2 Diabetes.

Insulin resistance and obesity are independently associated with type 1 diabetes (T1D) and are known risk factors for cardiovascular and kidney diseases, the leading causes of death in T1D. We evaluated the effect of BMI on cardiovascular and kidney outcomes in youth with T1D versus control youth with normal weight or obesity and youth with type 2 diabetes (T2D). Pubertal youth (n = 284) aged 12-21 years underwent assessments of resting heart rate (RHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), leptin, hs-CRP, adiponectin, ratio of urine albumin to creatinine, and estimated glomerular filtration rate. Participants with T1D underwent bicycle ergometry for VO2peak, monitoring for peripheral brachial artery distensibility (BAD), endothelial function testing for reactive hyperemic index, and aortic MRI for central arterial stiffness or shear. In adolescents with T1D, RHR, SBP, DBP, mean arterial pressure, leptin, hs-CRP, and hypertension prevalence were significantly higher, and BAD, descending aorta pulse wave velocity, and VO2peak lower with an obese versus normal BMI. Although hypertension prevalence and RHR were highest in obese adolescents with T1D and adiponectin lowest in youth with T2D, other measures were similar between obese adolescents with T1D and those with T2D. Obesity, now increasingly prevalent in people with T1D, correlates with a less favorable cardiovascular and kidney risk profile, nearly approximating the phenotype of youth with T2D. Focused lifestyle management in youth-onset T1D is critically needed to reduce cardiovascular risk.

1063-P: Effects of Bromocriptine Quick-Release (BCQR) Therapy on Glycemic Control, Insulin Sensitivity, and Vascular Function in Type 1 Diabetes (T1D)

BCQR is approved for adjunct therapy in type 2 diabetes (T2D). BCQR improves glycemic control and appears to reduce cardiovascular events in T2D. People with T1D have decreased insulin sensitivity (IS), correlating with vascular dysfunction. We evaluated the effects of BCQR on glycemic control, estimated IS, and vascular function in a random order, placebo-controlled crossover study of a 4-week intervention with BCQR in adolescents (12-21 yrs) and adults (22-60 yrs) with T1D. Outcomes included: insulin total daily dose (TDD), urine albumin to creatinine ratio (UACR), vascular markers using Dynapulse and EndoPAT, CGM, estimated IS scores (from CACTI and RESISTANT study models), and a mixed meal tolerance test (MMTT). Treatment effect was examined in mixed models and reported as LS mean ± SE adjusted for age, sex, phase, and treatment order. Interactions were examined by age and diabetes duration (DD). Participants‡ (n=84) were 50% adult, age 28.6 ± 14.5 yrs, 44% male, and 49% lean, with HbA1c 7.8% [7, 8.5] and DD 14.2 ± 11.7 yrs. Insulin TDD, log UACR, and CGM outcomes (average glucose, SD, % time BG&amp;gt;180 or &amp;lt;70 mg/dL) did not differ by treatment. SBP was lower on BCQR (114 ± 1.2 vs. 118 ± 1.2, p=0.0001). DBP was lower on BCQR in those with DD&amp;gt;5 yrs (68 ± 1.2 vs. 72 ± 1.2, p=0.0038). Reactive hyperemia index (endothelial function estimate) was lower on BCQR in adolescents (2.03 ± 0.12 vs. 2.32 ± 0.12, p=0.0039), and systemic vascular resistance (SVR) was lower on BCQR in adults (1408 ± 62 vs. 1479 ± 63, p=0.006). Dynapulse cardiac output and brachial artery distensibility did not differ by treatment. MMTT triglyceride (TG) peak minus baseline was lower on BCQR (22 ± 3.0 vs. 27 ± 2.9, p=0.0360). IS measured by MMTT fasting and AUC glucose/insulin, and by CACTI and RESISTANT scores, did not differ by treatment. In sum, BCQR did not affect CGM glycemia or estimated IS, but it improved cardiovascular measures such as SBP, DBP, SVR, and TG. ‡Mean ± SD or Median [Interquartile Range]. Disclosure S. Tell: None. J.K. Snell-Bergeon: Stock/Shareholder; Self; GlaxoSmithKline plc. T.B. Vigers: None. A. Baumgartner: None. E. Lyon: None. S. Gross: None. M. Schäfer: None. S. Polsky: None. K.J. Nadeau: None. I.E. Schauer: None. Funding JDRF (3-SRA-2015-125-M-R)

Abstract P137: Women Experience A Greater Decline In Brachial Artery Distensibility With Age Than Men

Introduction: Brachial artery distensibility is reduced in type 1 diabetes and can predict future coronary artery disease (CAD). Although women generally have reduced cardiovascular risk as compared with men, type 1 diabetes increases cardiovascular risk to a greater degree in women such that their cardiovascular risk matches that in men. Sex differences in arterial distensibility may contribute to the increased cardiovascular risk in women with type 1 diabetes. Hypothesis: We tested the hypothesis that brachial distensibility differed by sex and by diabetes status in a cohort of adults with and without type 1 diabetes. Methods: We measured brachial distensibility via DynaPulse instrument (PulseMetric, San Diego, CA) in 268 adults with type 1 diabetes (mean age 44±9 years) and 373 adults without diabetes (mean age 47 ±8 years) who completed clinical study visits 8±0.89 years apart. A linear mixed model was used to calculate mean brachial distensibility by age at the study visits in men and women by diabetes status. This model was adjusted for age, sex, diabetes status, and visit number. An age group*sex*diabetes interaction was used to calculate least squares means (LSmeans) brachial distensibility and examine trends in each stratum of interest. Results: Brachial distensibility decreases with increasing age (Figure 1). This reduction is greatest for women with type 1 diabetes and smallest for men without diabetes, with decreases from the oldest to youngest age group of 2.6 %/mmHg and 0.98 %/mmHg, respectively. Prior to the age of 40 years, women have better brachial distensibility than men regardless of diabetes status, while men have better brachial distensibility than women beginning in the 40-45 years age group. Conclusions: Women experience a steeper decline in their brachial distensibility than men regardless of diabetes status. Rapid reduction in brachial distensibility may contribute to the increases in cardiovascular risk in women with type 1 diabetes.

Elevated copeptin, arterial stiffness, and elevated albumin excretion in adolescents with type 1 diabetes

We sought to evaluate copeptin concentrations in adolescents with and without type 1 diabetes (T1D) and examine the associations between copeptin and measures of arterial stiffness and kidney dysfunction. This analysis included 169 adolescents with T1D (12-19 years of age, 59% girls, mean HbA1c 9.0 ± 1.5% and diabetes duration of 8.6 ± 2.9 years), in addition to 61 controls without T1D. Arterial stiffness including carotid-femoral pulse wave velocity (CF-PWV), carotid-radial PWV (CR-PWV), augmentation index normalized to heart rate of 75 bpm (AIx@HR75), and brachial artery distensibility (BAD). Serum copeptin, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) by serum creatinine and cystatin C were also assessed. Compared to controls, adolescents with T1D had higher median (Q1-Q3) copeptin (7.5 [5.2-11.3] vs 6.4 [4.8-8.3] pmol/L, P = .01), mean ± SD eGFR (121 ± 23 vs 112 ± 16 mL/min/1.73m2 , P = .002) and lower BAD (7.1 ± 1.3 vs 7.2 ± 1.2%, P = .02). Adolescents with T1D in the in high tertile copeptin group (>9.1 pmol/L) had higher AIx@HR75 (10.7 ± 1.2 vs 5 ± 1.2, P = .001), CR-PWV (5.30 ± 1.0 vs 5.18 ± 1.0 m/s, P = .04), and UACR (12 ± 1 vs 8 ± 1 mg/g, P = .025) compared to those in low tertile (<5.8 pmol/L) after adjusting for age, sex, and eGFR. Copeptin inversely associated with CF-PWV independent of age, sex, eGFR, SBP, and HbA1c in T1D adolescents. Our data demonstrate that elevated copeptin was associated with worse arterial stiffness in adolescents with T1D. These findings suggest that copeptin could improve CVD risk stratification in adolescents with T1D.

216-OR: Cardiovascular (CV) Impact of BMI in Youth with Type 1 Diabetes (T1D)

Insulin resistance (IR) and obesity are independently associated with T1D and are known risk factors for CV disease, the leading cause of mortality in T1D. We evaluated the impact of BMI on CV outcomes in T1D youth and compared obese T1D (OT1D) youth to youth with type 2 diabetes (T2D). Pubertal youth aged 12-21 years with T1D and T2D were recruited from the RESistance to InSulin in type 1 and type 2 diabetes (RESISTANT) and Effects of MEtformin on CardiovasculaR Function in AdoLescents with type 1 Diabetes (EMERALD) cohorts. Participants were stratified as lean (LT1D), overweight, or obese T1D or T2D (Table). CV outcomes included resting heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), leptin, hsCRP, and adiponectin. T1D participants performed bicycle ergometry for peak oxygen consumption (VO2peak), brachial artery (BA) distensibility by Dynapulse, and aortic MRI. HR, SBP, DBP, mean arterial pressure, and prevalence of hypertension were higher and BA distensibility, descending aorta oscillatory shear index, VO2peak, leptin, and hsCRP were worsened in OT1D vs. LT1D. Beyond hypertension prevalence in OT1D vs. T2D, which was worse in OT1D, T2D did not differ significantly from OT1D. Higher BMI, which is increasingly prevalent in T1D, is associated with a worsened CV profile in T1D youth, nearly approximating the CV phenotype of T2D youth. Closer attention to lifestyle management in T1D youth is needed to help reduce CV risk. Disclosure K.L. Tommerdahl: None. K.V. Baumgartner: None. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. A. Baumgartner: None. L. Pyle: None. J.G. Regensteiner: None. J.E.B. Reusch: Board Member; Self; American Diabetes Association. Other Relationship; Self; Merck &amp; Co., Inc. K.J. Nadeau: None. Funding American Diabetes Association (7-11-CD-08 to K.J.N.); JDRF (11-2010-343); National Institutes of Health (1R56DK088971-01)

Brachial artery stiffening in healthy primigravidas is associated with weight gain and increased cardiac output

ABSTRACTObjective: To assess brachial artery distensibility and associated factors in healthy primigravidas.Methods: We assessed brachial artery distensibility using the DynaPulse 5,000A in 37 women each trimester, and 6–8 weeks and 1–5 years postpartum. Associations with physical and cardiometabolic measures were considered.Results: Mean (SE) brachial artery distensibility (%Δ/mmHg) decreased (stiffened) from 7.50 (0.20) 12–14 weeks to 6.93 (0.22) 36–38 weeks (p < .01) and returned to baseline 7.52 (0.44) at 2.7 years postpartum. Weight gain and greater cardiac output were significantly related to greater stiffness.Conclusion: Increased weight and cardiac output of pregnancy were associated with brachial artery stiffening.