Progression of Coronary Artery Calcification in Type 1 Diabetes

Snell‐Bergeon, Janet K.; Hokanson, John E.; Jensen, L. E.; MacKenzie, Todd A.; Kinney, Gregory L.; Dabelea, Dana; Eckel, Robert H.; Ehrlich, James; Garg, Satish K.; Rewers, Marian

doi:10.2337/diacare.26.10.2923

Cited by 136 publications

(98 citation statements)

References 34 publications

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“…Two studies (18,19) failed to demonstrate a relationship between glycemia and CAC in type 1 diabetes, whereas one did (20). These studies showed relationships with traditional CVD risk factors, but a smaller sex difference in CAC than is usual for the nondiabetic population, consistent with the reduction in the difference between sexes for CAD in type 1 diabetes.…”

supporting

confidence: 48%

The Effect of Intensive Glycemic Treatment on Coronary Artery Calcification in Type 1 Diabetic Participants of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

et al. 2006

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The Epidemiology of Diabetes Interventions and Complications (EDIC) study, an observational follow-up of the Diabetes Control and Complications Trial (DCCT) type 1 diabetes cohort, measured coronary artery calcification (CAC), an index of atherosclerosis, with computed tomography (CT) in 1,205 EDIC patients at ϳ7-9 years after the end of the DCCT. We examined the influence of the 6.5 years of prior conventional versus intensive diabetes treatment during the DCCT, as well as the effects of cardiovascular disease risk factors, on CAC. The prevalences of CAC >0 and >200 Agatston units were 31.0 and 8.5%, respectively. Compared with the conventional treatment group, the intensive group had significantly lower geometric mean CAC scores and a lower prevalence of CAC >0 in the primary retinopathy prevention cohort, but not in the secondary intervention cohort, and a lower prevalence of CAC >200 in the combined cohorts. Waistto-hip ratio, smoking, hypertension, and hypercholesterolemia, before or at the time of CT, were significantly associated with CAC in univariate and multivariate analyses. CAC was associated with mean HbA 1c (A1C) levels before enrollment, during the DCCT, and during the EDIC study. Prior intensive diabetes treatment during the DCCT was associated with less atherosclerosis, largely because of reduced levels of A1C during the DCCT. Diabetes 55: 3556 -3565, 2006 P atients with type 1 diabetes have a high risk of developing cardiovascular disease (CVD), which in young adulthood can be 10-fold higher than in the general population (1,2). The reasons for this increased risk have not been fully elucidated and can only be partly explained by standard cardiovascular risk factors. Surprisingly, cumulative hyperglycemia has not been shown consistently to be a risk factor for cardiovascular events in type 1 diabetes (3-8).The Diabetes Control and Complications Trial (DCCT)/ Epidemiology of Diabetes Interventions and Complications (EDIC) study provides an opportunity to explore the complex relationships among traditional CVD risk factors, glycemia, and CVD outcomes (9). The DCCT demonstrated the importance of glycemic control in preventing or delaying microvascular complications (10), but it did not reach a clear conclusion with respect to macrovascular complications, owing to the low prevalence of macrovascular disease in the relatively young cohort (11). The long-term EDIC follow-up included assessments of subclinical CVD with measurement of carotid intima-media thickness (IMT) (12,13) and with computerized tomography (CT) of the heart to detect and quantitate calcification in the coronary arteries, a marker of atherosclerosis (14). The EDIC study demonstrated a significant protective effect of prior intensive diabetes therapy, compared with conventional therapy, on the progression of IMT over a 6-year period that was associated with the level of HbA 1c (A1C) (13). Progression of IMT was associated with the level of glycemia (A1C) over time, consistent with some (15), but not all (16,17), reports in type 1 di...

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supporting

confidence: 48%

The Effect of Intensive Glycemic Treatment on Coronary Artery Calcification in Type 1 Diabetic Participants of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

et al. 2006

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“…In view of the increasing perception of the serious cardiovascular risk already present in young T1DM patients (32) and 460 of its rapid progression in young adults (33), early intervention should target the modifiable risk factors in genetically predisposed individuals (with a positive family history of atherosclerosis). Although metabolic control remains the primordial therapeutic target in these patients, it does not explain the total coronary artery disease risk in T1DM (34).…”

Section: Endothelium and Sod In Diabetic Childrenmentioning

confidence: 99%

Impact of Oxidative Stress on the Endothelial Dysfunction of Children and Adolescents With Type 1 Diabetes Mellitus: Protection by Superoxide Dismutase?

et al. 2007

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Diabetes mellitus is associated with endothelial dysfunction and oxidative stress (OS). We investigated whether these abnormalities are interrelated in children and adolescents with type 1 diabetes mellitus (T1DM) and if early OS markers predictive of vascular dysfunction can be identified. Thirty-five T1DM patients were matched for sex, age, height, and weight with nondiabetic subjects as healthy controls (CO). Flow-mediated dilatation (FMD), carotid intima media thickness (IMT), and OS status in fasting blood were measured. Diabetic children had impaired FMD (6.68 Ϯ 1.98 versus 7.92 Ϯ 1.60% in CO, p ϭ 0.004), which was more pronounced in boys. The degree of FMD impairment was not related to the lower plasma levels of antioxidants or to the higher glucose, glycation, lipids, and peroxidation products. Erythrocyte superoxide dismutase activity, copper/zinc superoxide dismutase (Cu/Zn SOD), was higher in diabetic subjects (1008 Ϯ 224 versus 845 Ϯ 195 U/g Hb in CO, p ϭ 0.003) and was positively associated with FMD. After correcting for diabetes and gender, the subgroup of children with high Cu/Zn SOD (Ͼ955 U/g Hb) had a significantly better FMD (p ϭ 0.035). These results suggest that higher circulating Cu/Zn SOD could protect T1DM children and adolescents against endothelial dysfunction. Low Cu/Zn SOD is a potential early marker of susceptibility to diabetic vascular disease. (Pediatr Res 62: 456-461, 2007) D iabetes mellitus is an important risk factor for atherosclerosis and both the incidence and mortality of cardiovascular disease are increased in diabetic patients (1). Among the various pathophysiological mechanisms mediating the atherosclerotic process, both oxidative stress (OS) and endothelial dysfunction occur at an early stage in animal models of diabetes (2).Oxidative stress is defined as the change in the pro-oxidant/ antioxidant balance in favor of the former, potentially leading to biologic damage to macromolecules and cell dysfunction (3). As a result of hyperglycemia, excessive pro-oxidants (free radicals and reactive oxygen species) are formed via autooxidation of glucose, nonenzymatic glycation and formation of advanced glycation end products, increased flux through the polyol and hexosamine pathways, and activation of protein kinase C. These processes also lead to decreased antioxidant defenses. Brownlee (4) has linked all these abnormalities to the excessive production of superoxide by the mitochondria.In children with type 1 diabetes mellitus (T1DM), increased OS has been reported to be present even shortly after diagnosis (5). Other reports showed the parallelism between OS and abnormal markers of endothelial cell function (such as ESelectin and ICAM-1) in young T1DM patients, suggesting a link between these two abnormalities (6). Ultrasound testing of skin microcirculation and of brachial artery flow-mediated dilatation (FMD) have demonstrated early endothelial dysfunction in diabetic children and adolescents (7).Since it has been shown that foam cell accumulation in the vascular w...

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“…5 Although CAC is associated with measures of obesity obtained at the same time as the CAC measurement, 6 only one study has investigated the association between obesity and progression of CAC, and that study included only those with type I diabetes. 7 Thus, little is known about the role of obesity in the progression of CAC in asymptomatic individuals free of diabetes.…”

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confidence: 99%

Progression of Subclinical Coronary Atherosclerosis

et al. 2005

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Background-Obesity is associated with coronary artery calcification (CAC), a marker of the presence and extent of subclinical coronary atherosclerosis. Obesity adds incremental information in identifying those at higher risk of coronary heart disease to traditional risk factor assessment. The present study examined associations between obesity measures and progression of CAC in those at higher (Ն10%) and lower (Ͻ10%) 10-year coronary heart disease risk according to the Framingham risk equation. Methods and Results-In this study, 443 asymptomatic white individuals Ͼ30 years of age (243 men) had baseline and follow-up CAC measurements an average of 8.9 years apart. Multivariable linear regression models were fit to determine associations of obesity measures at baseline with progression of CAC defined as log e of the difference between follow-up and baseline CAC area plus 1 divided by time (in years) between examinations, adjusting for baseline CAC quantity, age, sex, baseline hypertension status, and baseline cholesterol level. Among 329 participants (74.3%) in the lower-risk group, waist circumference (Pϭ0.024), waist-to-hip ratio (PϽ0.001), body mass index (Pϭ0.036), and being overweight compared with being underweight or of normal weight (Pϭ0.008) were each significantly positively associated with progression of CAC. Among those at higher coronary heart disease risk, no baseline obesity measures were associated with CAC progression. Conclusions-Various measures of obesity were associated with increased progression of CAC in those at lower risk of coronary heart disease. Future studies examining the effectiveness of weight reduction strategies in reducing CAC progression among those with an otherwise favorable risk factor profile may be warranted.

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Progression of Coronary Artery Calcification in Type 1 Diabetes

Cited by 136 publications

References 34 publications

The Effect of Intensive Glycemic Treatment on Coronary Artery Calcification in Type 1 Diabetic Participants of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

The Effect of Intensive Glycemic Treatment on Coronary Artery Calcification in Type 1 Diabetic Participants of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

Impact of Oxidative Stress on the Endothelial Dysfunction of Children and Adolescents With Type 1 Diabetes Mellitus: Protection by Superoxide Dismutase?

Progression of Subclinical Coronary Atherosclerosis

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