Modifiable Risk Factors for Cardiovascular Disease in Children with Type 1 Diabetes: Can Early Intervention Prevent Future Cardiovascular Events?

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Term Occurence Count Dictionary
hyperlipidemia 3 endocrinologydiseases
hypoglycemia 1 endocrinologydiseases
metabolic syndrome 1 endocrinologydiseases
obesity 10 endocrinologydiseases
Insulin 3 endocrinologydiseasesdrugs
diabetic neuropathy 1 endocrinologydiseases
hyperglycemia 9 endocrinologydiseases
metformin 10 endocrinologydiseasesdrugs
Exenatide 1 endocrinologydiseasesdrugs
Liraglutide 1 endocrinologydiseasesdrugs
atorvastatin 4 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
Exenatide 29803 T1DM and have shown some potential benefit in terms of improving their cardiovascular health [[]]. Exenatide has been found to improve weight, insulin sensitivity, and lipoprotein particles in adults with T1DM
Insulin 14926 [[]]. In the study by Rodriguez et al., LDL-C was independently associated with CIMT [[]].Obesity, Insulin Resistance, and Lack of ExerciseContrary to the typical clinical picture of a thin patient with T1DM,
Insulin 17303 correlated to increased arterial stiffness in the previously mentioned SEARCH CVD study by Shah et al. [[]]. Insulin resistance (IR) or low insulin sensitivity is associated with obesity and metabolic syndrome. While
Insulin 27669 such trial is on-going and is expected to provide some evidence on this topic in the near future [[]]. Insulin Sensitizing and Incretin Mimetic MedicationsGiven the emerging role of insulin resistance in CVD risk
Liraglutide 29920 been found to improve weight, insulin sensitivity, and lipoprotein particles in adults with T1DM [[]]. Liraglutide use in adults with T1DM leads to reductions in their hypoglycemic events, total daily insulin dose,
atorvastatin 25424 medications on CVD outcomes. One randomized, double-blinded, cross-over pilot study of 12 weeks using 20 mg atorvastatin vs placebo showed no improvement on arterial stiffness and endothelial function on primary analysis,
atorvastatin 26132 with average age 15 ± 0.3 years, HbA1c 8.8 ± 0.2%, and diabetes duration 6.8 ± 0.5 years to atorvastatin 20 mg daily or placebo for 6 months [[]]. Patients were enrolled if they had LDL-C > 100 mg/dl
atorvastatin 26341 LDL-C > 100 mg/dl and BMI < 95th percentile and excluded in they had LDL-C > 160 mg/dl [[]]. Patients in the atorvastatin group had a baseline HbA1c that was significantly lower than the HbA1c of the placebo group but otherwise
atorvastatin 26561 were not different in terms of their age, sex, race, and Tanner stage. The authors showed again that atorvastatin was overall safe and well-tolerated and one subject developed elevated creatinine kinase, which normalized
metformin 3101 “microalbuminuria,” “arterial stiffness,” and “depression” as well as “statin,” “ metformin ,” “ACE inhibitor,” “non-insulin therapies,” “lifestyle,” and “intervention.” We also
metformin 27799 Incretin Mimetic MedicationsGiven the emerging role of insulin resistance in CVD risk in youth with T1DM, metformin —which improves insulin resistance—has been used as adjuvant treatment off label by pediatric endocrinologists
metformin 28066 Recent randomized controlled pediatric studies have failed to demonstrate a significant benefit of metformin in improving glycemic control [[], []]. A large multicenter double-blind, placebo-controlled randomized
metformin 28338 with an average 15.3 ± 1.7 years and diabetes duration 7.0 ± 3.3 years and treated them with metformin or placebo for 26 weeks [[]]. The authors failed to demonstrate improvements in HbA1c or in the LDL-C,
metformin 28488 authors failed to demonstrate improvements in HbA1c or in the LDL-C, HDL, or total cholesterol; however, metformin decreased total daily dose and measurements of adiposity, in accordance with other similar studies [[],
metformin 28699 [[], []].A systematic review and meta-analysis examined data from 325 patients with T1DM treated with metformin as adjuvant to insulin therapy [[]] .The authors concluded that metformin has no benefit in improving
metformin 28773 patients with T1DM treated with metformin as adjuvant to insulin therapy [[]] .The authors concluded that metformin has no benefit in improving glycemic control but it can lead to modest reduction in the total daily
metformin 28932 it can lead to modest reduction in the total daily dose of insulin and the BMI, which suggests that metformin could be helpful in decreasing weight gain associated with insulin use and indirectly improve cardiovascular
metformin 29163 youth with T1DM [[]]. Another study was a 9-month randomized, double-blind, placebo controlled trial of metformin and placebo in 28 children with T1DM [[]]. The authors showed no improvements in glycemic control or
metformin 29437 to the smaller size of the study [[]]. An ongoing clinical trial aims to investigate the effect of metformin directly on CVD measurements such as flow-mediated dilation and carotid and aortic intima-media thickness
Select Disease Character Offset Disease Term Instance
diabetic neuropathy 23279 children as young as 7 or 8 years old [[]].Autonomic DysfunctionWhile autonomic dysfunction is a sign of diabetic neuropathy , it has a direct effect on cardiovascular health for patients with T1DM because it affects the autonomic
hyperglycemia 997 arterial stiffness, and endothelial and myocardial dysfunction. Modifiable risk factors for CVD include hyperglycemia , hyperlipidemia, obesity, hypertension, depression, and autonomic dysfunction. Very few randomized controlled
hyperglycemia 1844 life, and by the time they are young adults, most of them have been potentially exposed to chronic hyperglycemia for more than two decades. By the time they reach 55 years of age, 35% of patients with T1D will die
hyperglycemia 10543 Trial (DCCT) that has the longest follow-up (30 years) of adult patients with T1DM have shown that hyperglycemia as assessed by mean HbA1c correlated significantly with the longitudinal changes in all of the traditional
hyperglycemia 11059 multivariate models assessed the association of traditional and novel risk factors—such as hypertension, hyperglycemia defined by average HbA1c, duration of diabetes, nephropathy, hypoglycemic events, hyperlipidemia, family
hyperglycemia 11549 similar results from cross-sectional and retrospective studies, indirectly assessing the effect of hyperglycemia on established CVD risk factors such as the LDL-C. In the SEARCH study, there were significantly higher
hyperglycemia 23009 to diabetes therapy and in the blood glucose monitoring and indirectly affect CVD risk by worsening hyperglycemia and subsequently lipoprotein profile as well [[]••, [], []]. The American Diabetes Association recommends
hyperglycemia 24287 follow-up of the Diabetes Control and Complications Trial (DCCT) cohort of adults with T1DM that improved hyperglycemia can improve significantly the cardiovascular outcomes and that glycemic control is closely correlated
hyperglycemia 30250 exenatide in eight children with T1DM showed decreased total insulin dose and improved post-prandial hyperglycemia ; however, the role of exenatide on CVD risk factors was not investigated [[]].Overall, more randomized
hyperglycemia 36406 Multiple modifiable risk factors contribute to their increased risk for CVD, such as dyslipidemia, hyperglycemia , obesity, insulin resistance, lack of exercise, depression, and autonomic dysfunction. Limited pediatric
hyperlipidemia 1012 and endothelial and myocardial dysfunction. Modifiable risk factors for CVD include hyperglycemia, hyperlipidemia , obesity, hypertension, depression, and autonomic dysfunction. Very few randomized controlled studies
hyperlipidemia 11155 hypertension, hyperglycemia defined by average HbA1c, duration of diabetes, nephropathy, hypoglycemic events, hyperlipidemia , family history of diabetes, and smoking—with major atherosclerotic cardiovascular events in the DCCT
hyperlipidemia 21884 that microalbuminuria can be mediated by the presence of other CVD risk factors such as hypertension, hyperlipidemia , and IR [[]]. Microalbuminuria can also progress to macroalbuminuria and diabetic kidney disease, which
hypoglycemia 19352 []]. Youth with T1DM tends to exercise less than youth without diabetes, most likely due to fear of hypoglycemia due to insulin [[]••, []]. Studies have shown that youth with T1DM who exercises more have better
metabolic syndrome 17385 Shah et al. [[]].Insulin resistance (IR) or low insulin sensitivity is associated with obesity and metabolic syndrome . While traditionally IR (or low insulin sensitivity) has been thought to be part of the pathophysiology
obesity 1028 and myocardial dysfunction. Modifiable risk factors for CVD include hyperglycemia, hyperlipidemia, obesity , hypertension, depression, and autonomic dysfunction. Very few randomized controlled studies have been
obesity 15036 Resistance, and Lack of ExerciseContrary to the typical clinical picture of a thin patient with T1DM, obesity is very common today in children with T1DM. Based on baseline data in the T1D Exchange registry obtained
obesity 15292 average age of 15.4 ± 1.4 years and HbA1c 8.7 ± 1.8%, overweight status was present in 22.9% and obesity was present in 13.1% in the overall sample [[]]. Obesity was highest among girls (40.8%) and adolescents
obesity 15804 duration of 4.7 ± 3.0 years [[]]. In the European study, factors that were associated with increased obesity during the course of diabetes were higher insulin doses, female gender, low BMI at diabetes onset, intensified
obesity 16174 higher BMI z score than the international and their respective normal national data, indicating that obesity among children with T1DM is a significant problem [[]]. This is in accordance with adult data from the
obesity 16439 higher insulin doses also had increased weight gain and higher total cholesterol and LDL-C, central obesity , insulin resistance, blood pressure, more coronary artery calcifications, and higher CIMT on follow-up,
obesity 16574 pressure, more coronary artery calcifications, and higher CIMT on follow-up, underlying the role of obesity in promoting CVD in patients with T1DM [[]].Obesity is associated with atherogenic lipoproteins in youth
obesity 17373 CVD study by Shah et al. [[]].Insulin resistance (IR) or low insulin sensitivity is associated with obesity and metabolic syndrome. While traditionally IR (or low insulin sensitivity) has been thought to be part
obesity 31920 diabetes association recommends lifestyle change as the first line treatment to address high cholesterol, obesity , and hypertension in youth with diabetes [[]]. A few randomized trials have looked at the effect of
obesity 36421 modifiable risk factors contribute to their increased risk for CVD, such as dyslipidemia, hyperglycemia, obesity , insulin resistance, lack of exercise, depression, and autonomic dysfunction. Limited pediatric randomized

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