scholarly journals 30-Year Cardiovascular Disease in Type 1 Diabetes: Risk and Risk Factors Differ by Long-Term Patterns of Glycemic Control

2021 ◽  
Author(s):  
Rachel G. Miller ◽  
Trevor J. Orchard ◽  
Tina Costacou

<b>Objective:</b> We hypothesized that there is heterogeneity in long-term patterns of glycemic control with respect to cardiovascular disease (CVD) development in type 1 diabetes and that risk factors for CVD differ by glycemic control pattern. Thus, we estimated associations between data-derived latent HbA1c trajectories and 30-year CVD risk in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood-onset (<17 years old) type 1 diabetes.<b> </b> <p><b>Research Design and Methods: </b>Participants (n=536 with ≥2 HbA1c measurements [median 6] and CVD-free at baseline; mean age 27 and diabetes duration 18 years) were followed from 1986-88 to 2016-18 to ascertain CVD incidence (CVD death, myocardial infarction, stroke, coronary revascularization or blockage ≥50%, ischemic ECG, or angina). Latent HbA1c trajectories and their association with time-to-CVD incidence were simultaneously assessed using Joint Latent Class Mixed Models.</p> <p><b>Results:</b> Two HbA1c trajectories with respect to differential CVD risk were identified: Low (HbA1c ~8% [64 mmol/mol] and improving over follow-up, 76% of cohort) and High (HbA1c ~10% [86 mmol/mol] and stable, 24%). Overall, 30-year CVD incidence was 47.4% (n=253); MACE incidence 31.0% (n=176). High HbA1c was associated with 3-fold increased CVD risk versus Low HbA1c. Both groups had similar age and diabetes duration. Non-HDLc and estimated glomerular filtration rate were associated with CVD risk only in Low HbA1c; albumin excretion rate was associated with CVD risk only in High HbA1c.<b> </b></p> <p><b>Conclusions: </b>These risk factor differences suggest that pathways to CVD may differ by glycemic control, potentially resulting in important implications for prognosis in type 1 diabetes.</p>

2021 ◽  
Vol 12 ◽  
Author(s):  
Eva O. Melin ◽  
Ralph Svensson ◽  
Jonatan Dereke ◽  
Magnus Hillman

Aims: Alexithymia has been linked to cardiovascular disease. The aim was to explore whether the immuno-inflammatory variables galectin-3 binding protein (Gal3BP), soluble (s)CD163 and galectin-3 were independently associated with alexithymia, while controlling for known risk factors for cardiovascular disease, such as depression, anxiety, impaired glycemic control, obesity, smoking, and physical inactivity in patients with type 1 diabetes (T1D).Methods: Cross-sectional design. The participants were consecutively recruited from one diabetes out-patient clinic. Alexithymia, depression and anxiety were assessed by self-report instruments. Blood samples, anthropometrics, and blood pressure were collected, supplemented with data from electronic health records. High Gal3BP was defined as ≥3.3 μg/ml, high sCD163 as ≥0.6 μg/ml, high galectin-3 as ≥2.6 ng/ml, impaired glycemic control as HbA1c &gt;70 mmol/mol (&gt;8.6%) and abdominal obesity as waist circumference ≥ 1.02 m for men and ≥ 0.88 m for women.Results: Two hundred and ninety two patients participated (men 56%, aged 18–59 years, alexithymia prevalence 15%). Patients with alexithymia had higher prevalence of depression (34 vs. 6%, p &lt; 0.001), anxiety (61 vs. 30%, p &lt; 0.001), high Gal3BP levels (39 vs. 17%, p = 0.004), high HbA1c levels (46 vs. 24%, p = 0.006), and abdominal obesity (29 vs. 15%, p = 0.045). Depression [adjusted odds ratio (AOR) 6.5, p &lt; 0.001], high Gal3BP levels (AOR 2.4, p = 0.035), and age (AOR 0.96, p = 0.027) were independently associated with alexithymia. Abdominal obesity (AOR 4.0, p &lt; 0.001), high Gal3BP levels (AOR 2.8, p = 0.002), and depression (AOR 2.9, p = 0.014) were associated with high HbA1c. Abdominal obesity and anxiety were associated [Crude odds ratio (COR) 2.4, p = 0.006].Conclusions: T1D patients with alexithymia had higher prevalence of high Gal3BP levels, depression, impaired glycemic control, anxiety, and abdominal obesity, which are known risk factors for cardiovascular disease. Only high Gal3BP levels, depression, and younger age were independently associated with alexithymia in adult patients with T1D.


2020 ◽  
Vol 105 (5) ◽  
pp. e2032-e2038 ◽  
Author(s):  
Viral N Shah ◽  
Ryan Bailey ◽  
Mengdi Wu ◽  
Nicole C Foster ◽  
Rodica Pop-Busui ◽  
...  

Abstract Context Cardiovascular disease (CVD) is a major cause of mortality in adults with type 1 diabetes. Objective We prospectively evaluated CVD risk factors in a large, contemporary cohort of adults with type 1 diabetes living in the United States. Design Observational study of CVD and CVD risk factors over a median of 5.3 years. Setting The T1D Exchange clinic network. Patients Adults (age ≥ 18 years) with type 1 diabetes and without known CVD diagnosed before or at enrollment. Main Outcome Measure Associations between CVD risk factors and incident CVD were assessed by multivariable logistic regression. Results The study included 8,727 participants (53% female, 88% non-Hispanic white, median age 33 years [interquartile ratio {IQR} = 21, 48], type 1 diabetes duration 16 years [IQR = 9, 26]). At enrollment, median HbA1c was 7.6% (66 mmol/mol) (IQR = 6.9 [52], 8.6 [70]), 33% used a statin, and 37% used blood pressure medication. Over a mean follow-up of 4.6 years, 325 (3.7%) participants developed incident CVD. Ischemic heart disease was the most common CVD event. Increasing age, body mass index, HbA1c, presence of hypertension and dyslipidemia, increasing duration of diabetes, and diabetic nephropathy were associated with increased risk for CVD. There were no significant gender differences in CVD risk. Conclusion HbA1c, hypertension, dyslipidemia and diabetic nephropathy are important risk factors for CVD in adults with type 1 diabetes. A longer follow-up is likely required to assess the impact of other traditional CVD risk factors on incident CVD in the current era.


2021 ◽  
Author(s):  
Valma Harjutsalo ◽  
Drazenka Pongrac Barlovic ◽  
Daniel Gordin ◽  
Carol Forsblom ◽  
George King ◽  
...  

<b>Objective</b> <p>The aim of this study was to determine the incidence of cardiovascular disease (CVD) and mortality as well as their risk factors in type 1 diabetes (T1D) with more than 50-years duration. </p> <p><b>Methods</b><b></b></p> <p>From 5,396 individuals included in the Finnish Diabetic Nephropathy Study, 729 diagnosed in 1967 or earlier survived with T1D for more than 50 years. In this FinnDiane 50-year cohort, cumulative incidence of CVD events was assessed from the diagnosis of diabetes, and the excess CVD risk, compared to matched 12,710 individuals without diabetes, was calculated by Fine and Gray’s method. In addition, at the baseline visit (median duration of diabetes of 39 years) risk factors for different types of CVD (both non-fatal and fatal) and mortality were analyzed and cause-specific hazard ratios were estimated during a median follow-up of 16.6 years from the baseline visit. </p> <p><b>Results</b> </p> <p>In individuals with diabetes duration of more than 50 years, the 60-year cumulative incidence of CVD from the diagnosis of diabetes was 64.3% (62.5-66.0). Compared to individuals without diabetes, the standardized incidence ratio for CVD was 7.4 (6.5-8.3) and was in persons with normoalbuminuria 4.9 (4.0-5.9). Mean HbA<sub>1c</sub> and HbA<sub>1c</sub> variability, dyslipidemia, BMI, kidney disease, age and diabetes duration were the variables associated with incident CVD. In particular, HbA<sub>1c </sub>was associated with peripheral artery disease (PAD). Standardized mortality ratio compared with the Finnish background population was 3.2 (2.8-3.7). The factors, associated with mortality were diabetes duration, increased HbA<sub>1c</sub> variability, inflammation, insulin resistance, kidney disease and PAD.</p> <p><b> </b></p> <p><b>Conclusions</b></p> <p>Individuals with T1D of very long duration are at a high risk of CVD. In addition, throughout the lifespan, optimal glycemic control remains central to CVD and excess mortality prevention. </p>


2021 ◽  
Vol 22 (19) ◽  
pp. 10192
Author(s):  
Darja Smigoc Schweiger ◽  
Tadej Battelino ◽  
Urh Groselj

Cardiovascular disease (CVD) is the primary cause of higher and earlier morbidity and mortality in people with type 1 diabetes (T1D) compared to people without diabetes. In addition, women with T1D are at an even higher relative risk for CVD than men. However, the underlying pathophysiology is not well understood. Atherosclerotic changes are known to progress early in life among people with T1D, yet it is less clear when excess CVD risk begins in females with T1D. This review explores the prevalence of classical CVD risk factors (such as glycemic control, hypertension, dyslipidemia, obesity, albuminuria, smoking, diet, physical inactivity), as well as of novel biomarkers (such as chronic inflammation), in children and adolescents with T1D with particular regard to sex-related differences in risk profile. We also summarize gaps where further research and clearer clinical guidance are needed to better address this issue. Considering that girls with T1D might have a more adverse CVD risk profile than boys, the early identification of and sex-specific intervention in T1D would have the potential to reduce later CVD morbidity and excess mortality in females with T1D. To conclude, based on an extensive review of the existing literature, we found a clear difference between boys and girls with T1D in the presence of individual CVD risk factors as well as in overall CVD risk profiles; the girls were on the whole more impacted.


2021 ◽  
Author(s):  
Valma Harjutsalo ◽  
Drazenka Pongrac Barlovic ◽  
Daniel Gordin ◽  
Carol Forsblom ◽  
George King ◽  
...  

<b>Objective</b> <p>The aim of this study was to determine the incidence of cardiovascular disease (CVD) and mortality as well as their risk factors in type 1 diabetes (T1D) with more than 50-years duration. </p> <p><b>Methods</b><b></b></p> <p>From 5,396 individuals included in the Finnish Diabetic Nephropathy Study, 729 diagnosed in 1967 or earlier survived with T1D for more than 50 years. In this FinnDiane 50-year cohort, cumulative incidence of CVD events was assessed from the diagnosis of diabetes, and the excess CVD risk, compared to matched 12,710 individuals without diabetes, was calculated by Fine and Gray’s method. In addition, at the baseline visit (median duration of diabetes of 39 years) risk factors for different types of CVD (both non-fatal and fatal) and mortality were analyzed and cause-specific hazard ratios were estimated during a median follow-up of 16.6 years from the baseline visit. </p> <p><b>Results</b> </p> <p>In individuals with diabetes duration of more than 50 years, the 60-year cumulative incidence of CVD from the diagnosis of diabetes was 64.3% (62.5-66.0). Compared to individuals without diabetes, the standardized incidence ratio for CVD was 7.4 (6.5-8.3) and was in persons with normoalbuminuria 4.9 (4.0-5.9). Mean HbA<sub>1c</sub> and HbA<sub>1c</sub> variability, dyslipidemia, BMI, kidney disease, age and diabetes duration were the variables associated with incident CVD. In particular, HbA<sub>1c </sub>was associated with peripheral artery disease (PAD). Standardized mortality ratio compared with the Finnish background population was 3.2 (2.8-3.7). The factors, associated with mortality were diabetes duration, increased HbA<sub>1c</sub> variability, inflammation, insulin resistance, kidney disease and PAD.</p> <p><b> </b></p> <p><b>Conclusions</b></p> <p>Individuals with T1D of very long duration are at a high risk of CVD. In addition, throughout the lifespan, optimal glycemic control remains central to CVD and excess mortality prevention. </p>


2019 ◽  
Vol 7 (1) ◽  
pp. e000625 ◽  
Author(s):  
Stephanie Jones ◽  
Amal R Khanolkar ◽  
Evelien Gevers ◽  
Terence Stephenson ◽  
Rakesh Amin

BackgroundFor childhood onset type 1 diabetes (T1D), the pathogenesis of atherosclerosis is greatly accelerated and results in early cardiovascular disease (CVD) and increased mortality. However, cardioprotective interventions in this age group are not routinely undertaken.AimsTo document prevalence of cardiovascular risk factors from diagnosis of childhood T1D and their relationship with disease duration and ethnicity.MethodsRoutinely collected clinical records for 565 children with T1D were retrospectively analyzed. Data were collected from diagnosis and at routine check-ups at pediatric diabetes clinics across Barts Health National Health Service Trust. Age at diagnosis was 8.5 years (0.9–19.4). Mean follow-up 4.3 years (0–10.8). 48% were boys and 60% were non-white. Linear longitudinal mixed effects models were used to evaluate relationships between risk factors and diabetes duration.ResultsCVD risk factors were present at first screening; 33.8% of children were overweight or obese, 20.5% were hypertensive (elevated diastolic blood pressure (BP)) and total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were abnormal in 63.5%, 34.2% and 22.0%, respectively. Significant associations between diabetes duration and annual increases of body mass index (0.6 kg/m2), BP (0.1 SD score) and lipids (0.02–0.06 mmol/L) were noted. Annual increases were significantly higher in black children for BP and Bangladeshi children for lipids. Bangladeshi children also had greatest baseline levels.ConclusionsCVD risk factors are present in up to 60% of children at diagnosis of T1D and increase in prevalence during the early years of the disease. Commencing screening in younger children and prioritizing appropriate advice and attention to ethnic variation when calculating risk should be considered.


2021 ◽  
Vol 9 ◽  
Author(s):  
Scott T. Chiesa ◽  
M. Loredana Marcovecchio

Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in individuals with type 1 diabetes (T1D). Adolescence appears to be a critical time for the development of early subclinical manifestations of CVD, with these changes likely driven by a deterioration in glycemic control during the progression through puberty, combined with the emergence of numerous other traditional cardiometabolic risk factors (e.g., hypertension, dyslipidemia, smoking, alcohol use, obesity, etc.) which emerge at this age. Although hemoglobin A1C has long been the primary focus of screening and treatment strategies, glycemic control remains poor in youth with T1D. Furthermore, screening for cardiovascular risk factors—which are often elevated in youth with T1D—is suboptimal, and use of pharmacological interventions for hypertension and dyslipidemia remains low. As such, there is a clear need not only for better screening strategies for CVD risk factors in youth, but also early interventions to reduce these, if future CVD events have to be prevented. Accumulating evidence has recently suggested that early increases in urinary albumin excretion, even within the normal range, may identify adolescents with T1D who are at an increased risk of complications, and results from pharmacological intervention with statins and ACE inhibitors in these individuals have been encouraging. These data join a growing evidence highlighting the need for a whole-life approach to prevention starting from childhood if efforts to improve CVD outcomes and related mortality in T1D are to be maintained.


2021 ◽  
Author(s):  
Ionut Bebu ◽  
Sareh Keshavarzi ◽  
Xiaoyu Gao ◽  
Barbara H. Braffett ◽  
Angelo J. Canty ◽  
...  

<b>Background</b> The role of genetic factors on the risk of cardiovascular disease (CVD) risk in type 1 diabetes remains unknown. We therefore examined whether previously identified genetic factors for coronary artery disease (CAD) are associated with the risk of CVD <i>above and beyond</i> established demographic and clinical factors in The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. <p><b>Methods</b> Polygenic risk scores (PRS) and individual genetic variants identified in previous studies were obtained from genome-wide genotyping performed in 1371 DCCT/EDIC participants. Two composite CVD outcomes were considered: major adverse cardiovascular events (MACE) (CVD death or non-fatal myocardial infarction or stroke) and any-CVD (MACE plus confirmed angina, silent MI, revascularization, or congestive heart failure). Cox proportional hazards models assessed the association between the genetic factors and the risk of CVD when adjusted for other factors (including age, lipids, blood pressure and glycemia). </p> <p><b>Results</b> CAD PRS was strongly associated with the subsequent risk of any-CVD (42% and 38% higher risk per 1 standard deviation (SD) increase in unadjusted and fully adjusted models, respectively, p<0.0001), and with the risk of MACE (50% and 40% higher risk per 1SD increase in unadjusted and fully adjusted models, respectively, p<0.0001). Several individual SNPs were also nominally associated with the risk of any-CVD and MACE.</p> <p><b>Conclusions </b>Genetic factors are associated with the risk of subsequent cardiovascular disease in individuals with type 1 diabetes, above and beyond the effect of established risk factors such as age, lipids, blood pressure and glycemia. </p>


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