|Childhood Diabetes in Germany and Austria
Earlier identification and timely treatment of risk factors
may prevent future cardiovascular events.
BY K. OTFRIED SCHWAB, MD; JÜRGEN DOERFER, MD; and REINHARD W. HOLL, MD
for the DPV STUDY GROUP
|Type 1 diabetes is increasingly recognized as an independent risk factor for premature cardiovascular disease (CVD) and elevated cardiovascular death rate in patients aged 20 to 39 years.1 Postmortem studies in children and youth who died an unnatural death showed that the development of atherosclerotic lesions of the vessel wall starts in childhood, and that there is a close relationship to cardiovascular risk factors. My colleagues and I recently reported on this in Diabetes Care.2
In the Bogalusa Heart Study3 and the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study,4 the evaluation of premortal existing risk factors (HbA1c >8%, increased lipids, hypertension, obesity and smoking) verified their unfavorable influence on the progression of atherosclerosis.
Childhood and adolescent diabetes is commonly associated with additional risk factors. Therefore, this cross-sectional analysis of data from the German Diabetes Documentation and Quality Management System DPV was conducted to obtain reliable information on character and prevalence rate, as well as sex differences of potential atherogenic risk factors in 27,358 German children, adolescents and young adults with type 1 diabetes (Table 1).
ATHEROGENIC RISK FACTORS
Overall, 69% of 27,358 patients had one or more analyzed risk factor. The majority of patients showed one risk factor (53%), followed by patients with no risk factors (31%), two risk factors (14%) and three or four risk factors (2%).
The most frequently diagnosed nonlipid risk factor in our patients was HbA1c >7.5%. Poor glycemic control is particularly associated with the development of long-term microvascular complications.5 Further investigation may show that there is a direct relationship between HbA1c levels and the extent of atherosclerosis.
Gerstein et al6 found that intima-media thickness (IMT) increased 0.026 mm for every 0.9% increase in HbA1c (P<.0001). In another study, HbA1c >7.5% was identified as a strong risk factor for progression of coronary artery calcification in type 1 diabetes patients aged 22 to 50 years.7
Overweight (90th to 97th body mass index [BMI] percentile or BMI >25 kg/m2 ) and obesity (>97th BMI percentile or BMI >30 kg/m2 ) are thought to be cardiovascular risk factors with regard to the development of dyslipidemia, hypertension, type 2 diabetes and metabolic syndrome.8 If obese children become obese adults, one of the long-term consequences may be early atherosclerosis and increased cardiovascular morbidity.9 Twenty percent of our diabetic population had BMI >90th percentile.
According to the US National High Blood Pressure Education Program, hypertension is defined as systolic blood pressure and/or diastolic blood pressure ≥95th percentile by gender, age and height. Blood pressure between the 90th and 95th percentile is designated as prehypertension.10 In our patients, elevated systolic blood pressure was found in 8.2% and elevated diastolic blood pressure in 3.2%. Hypertension is regarded as an independent atherogenic risk factor and is positively correlated with increased carotid IMT in children and adolescents with type 1 diabetes.11,12
Smoking is a commonly accepted independent risk factor for atherosclerosis. The prevalence of smoking, nevertheless, is similar in diabetic patients compared with nondiabetic people.13 Despite the well-known health risk of smoking, >15% of our type 1 diabetes patients currently smoked.
Total cholesterol serves as a screening parameter for hypercholesterolemia. Values >200 mg/dL (>5.2 mmol/L) were defined as high risk14 and demonstrable in >26% of our patients.
LDL represents the principal atherogenic lipoprotein fraction. Plasma elevation >130 mg/dL (>3.4 mmol/L) was classified abnormal and concentrations >160 mg/dL (>4.1mmol/L) were used as the reference value for patients at high risk who require lipid-lowering pharmacotherapy if diet and lifestyle changes failed.14 In our patients, the percentage of LDL >130 mg/dL to 160 mg/dL was 11.8%, and 5.5% had LDL >160 mg/dL.
HDL particles are responsible for the reverse cholesterol transport from the periphery to the liver and have antiatherogenic activities. We considered HDL <35 mg/dL (<0.9 mmol/L) abnormal;14 this was found in 4.1 % of our diabetic population.
It is known that women with type 1 diabetes have an increased risk of developing CVD and, therefore, equalizing the advantageous sex difference seen in the general population.15 In our analysis, this is based on increased HbA1c, total cholesterol, LDL and BMI values in females compared with males who were conspicuous by elevated blood pressure and more frequent smoking.
MANAGEMENT OF RISK FACTORS
With regard to the management of additional atherogenic risk factors, there is a considerable discrepancy in juvenile type 1 diabetic patients between the high risk for future cardiovascular morbidity and the low treatment rate of modifiable risk factors such as hypertension and dyslipidemia. Although vascular complications are normally subclinical during childhood and adolescence, cardiovascular risk factors should be given our full attention to reduce risk by optimal metabolic control and lifestyle modification.16
Only if these efforts are insufficient is pharmacotherapy a reasonable form of treatment. It must be individualized based on type and number of atherogenic risk factors, family history and existing complications.
Hypertension in children and adolescents with type 1 diabetes may primarily be treated early with angiotensin-converting enzyme inhibitors. These agents have antihypertensive effects and reduce the incidence of microalbuminuria and nephropathy.17 In addition to hypertension, dyslipidemia is a common concomitant disease in patients with diabetes. The American Diabetes Association strongly recommends lipid-lowering pharmacotherapy for patients with LDL >160 mg/dL but for LDL between 130 mg/dL and 159 mg/dL only if nutrition therapy and lifestyle changes failed. In any case, the treatment target is LDL <100 mg/dL.18 So far, in a limited number of children with familial and severe hypercholesterolemia, statins showed good LDL cholesterol-lowering efficacy and a low rate of side effects.19
This representative analysis demonstrates the high frequency of atherogenic risk factors in children and adolescents with type 1 diabetes and underlines the importance of an early search for these cardiovascular risk factors. Significant sex differences were computed for most of the risk factors. The discrepancy between a high prevalence of cardiovascular risk factors and the low rate of antihypertensive and lipid-lowering treatment deserves special consideration.
Professor K. Otfried Schwab, MD, is from the Center for Children and Youth Medicine at the University of Freiburg Clinic, Freiburg, Germany. He may be reached at firstname.lastname@example.org. For the complete list of the DPV Study Group participating centers and sponsors see the original paper.
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19. Black DM. Statins in children: what do we know and what do we need to know? Curr Atheroscler Rep. 2001;3:29-34.
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