Cardiovascular risk in pediatric type 1 diabetes: sex-specific intima-media thickening verified by automatic contour identification and analyzing systems.

OBJECTIVES: To improve screening and quantification of subclinical atherosclerosis in children and adolescents with type 1 diabetes (T1D), we investigated the distribution of cardiovascular risk factors (cRFs) and carotid intima-media thickness (cIMT) percentiles with regard to sex-specific differences. METHODS: This cross-sectional analysis included clinical parameters, blood lipids, and B-mode ultrasound examination of the bilateral mean cIMT using an automatic contour identification procedure combined with computerized analysis. RESULTS: A total of 270 patients were eligible for evaluation (126 females, mean age 13.7 yr; 144 males, mean age 13.8 yr). In the total group, cIMT was significantly related to sex and diabetes duration but not to age. In males, cIMT was significantly higher than in females and sex-specific cIMT percentiles were calculated. Both pulse pressure and diabetes duration in boys and low-density lipoprotein (LDL)-cholesterol, hemoglobin A1c (HbA1c), and diabetes duration in girls showed a significant association with cIMT. CONCLUSIONS: On the basis of sex differences of cRFs and cIMT in pediatric T1D, the assessment of sex-specific IMT percentiles facilitates a differentiated interpretation of subclinical atherosclerosis. The underlying diabetes and additional cRFs seem to be more important determinants of intima-media thickening than age. To improve the comparability of IMT measurements of relevant studies, the international harmonization of IMT measurements should be aimed for.

Synergistic effects of elevated systolic blood pressure and hypercholesterolemia on carotid intima-media thickness in children and adolescents.

This study aimed to investigate the synergistic effects of elevated systolic blood pressure (SBP) and hypercholesterolemia on carotid intima-media thickness (cIMT). For this study, 60 children with hypercholesterolemia and 40 healthy control children were divided into four subgroups: hypercholesterolemic children with normal (<90th percentile) or elevated (>or= 90th percentile) SBP and control children with normal or elevated SBP. The highest mean and maximal cIMT values were found in the hypercholesterolemic children with elevated SBP and were significantly different from those of all the other groups. The synergistic effects of elevated SBP and hypercholesterolemia lead to a significant increase in cIMT as a subclinical sign of early atherosclerosis.

Marked smoking-associated increase of cardiovascular risk in childhood type 1 diabetes.

Type 1 diabetes is a generally accepted atherogenic risk factor, and diabetic patients who smoke markedly accelerate the atherosclerotic process. The main intentions of our investigation were to ascertain differences between juvenile active/passive smokers and non-smokers with type 1 diabetes regarding the number and spectrum of cardiovascular risk factors and their associations with smoking. Ninety-two patients were enrolled comprising 19 active/passive smokers (median age 15.9 years) and 73 non-smokers (median age 12.3 years). To determine age-dependent influences we compared age- and gender-matched groups of 12 smokers with 12 non-smokers. Smokers had significantly higher HbA1c, fructosamine, total cholesterol, LDL cholesterol, apolipoprotein B, serum P-selectin, and lower serum L-selectin than non-smokers. However, L-selectin levels were not different between the age-matched smoker and non-smoker groups. A significant positive relation (Spearman rank correlation) was found between smoking and age, HbAlc, fructosamine, total cholesterol, apolipoprotein B, and P-selectin; a negative relationship between smoking and L-selectin. We conclude that smoking in children and adolescents with type 1 diabetes increases the cardiovascular risk through the deterioration of glucose metabolism, lipid profile, and endothelial function. Therefore, smoking diabetic juveniles may increase their number of cardiovascular risk factors from 1, diabetes, by another four factors, i.e. smoking, hyperglycemia, dyslipidemia, and endothelial perturbation.

Early atherosclerosis in childhood type 1 diabetes: role of raised systolic blood pressure in the absence of dyslipidaemia.

The intentions of our investigation were (1) to search for atherogenic risk factors and signs of incipient atherosclerosis in children and adolescents with type 1 diabetes (T1DM) in comparison to well-matched control subjects, (2) to evaluate risk factor associations with carotid intima media thickness (cIMT) in diabetic patients and control subjects, and (3) to acquire a better knowledge of early atherogenesis in children and adolescents with and without T1DM. 94 diabetic children (age median 12.3 years, HbA1c median 7.7%) and 40 non-diabetic controls (age median 12.3 years) were investigated. Mean cIMT was determined using high-resolution B-mode ultrasound with an automated contour identification procedure. Compared to controls, subjects with diabetes had significantly elevated cIMT (p = 0.041) and systolic BP (p = 0.007) but showed a less atherogenic lipid profile. Most markers of inflammation, endothelial function and fibrinolytic activity were higher in diabetic subjects than in controls. Multiple linear regression analysis revealed a significant relationship (r = 0.53, p = 0.036) between bilateral mean cIMT and diverse risk factors in patients with T1DM. Spearman rank correlation showed that diabetes duration (rho = 0.32, p = 0.029), systolic BP (rho = 0.32, p = 0.004), weight (rho = 0.257, p = 0.022), and height (rho = 0.265, p = 0.018) significantly correlated with bilateral mean cIMT in the 94 diabetic patients. In conclusion, in well-controlled type 1 diabetic children systolic BP may be of greater importance than dyslipidaemia in early atherogenesis. BMI, markers of sustained inflammation, endothelial dysfunction and fibrinolytic activity are increased in diabetic versus non-diabetic children but none of them correlates significantly with cIMT. Their prognostic value remains to be determined.

Adult-like but regressive increase of intima-media thickness and roughness in a child with type 1 diabetes.

A 12-yr-old Kosovo-Albanian boy with insufficiently controlled type 1 diabetes since his second year of life developed severely increased intima-media thickness (IMT) and roughness (IMR) of the common carotid artery (CCA): max/mean IMT=0.81/0.68 mm and IMR=0.048 mm. Intima-media thickening, comparable with that in a 50- to 60-yr-old healthy adult, decreased within 41 months (max/mean carotid IMT=0.72/0.56 mm and IMR=0.036 mm) by intensive treatment of diabetes. Moyamoya disease (MMD), complicated by cerebral infarction, occurred coincidentally but regressed within 6 months. This case report points out that (i) chronic hyperglycemia in childhood may lead to adult-like increase of carotid IMT/IMR as early signs of subclinical atherosclerosis, (ii) increased carotid IMT/IMR may be regressive by intensive diabetes control, and (iii) a screening examination for carotid IMT/IMR should be considered in patients at high risk of atherosclerosis.

Pioglitazone reduces atherogenic dense LDL particles in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study.

OBJECTIVE: The oral antidiabetic agent pioglitazone improves insulin sensitivity and glycemic control and appears to lower atherogenic dense LDL in type 2 diabetes. Insulin resistance may occur frequently in nondiabetic patients with hypertension. This study is the first to report the effect of pioglitazone on LDL subfractions in normolipidemic, nondiabetic patients with arterial hypertension. RESEARCH DESIGN AND METHODS: We performed a monocentric, double-blind, randomized, parallel-group comparison of 45 mg pioglitazone (n = 26) and a placebo (n = 28), each given once daily for 16 weeks. Fifty-four moderately hypertensive patients (LDL cholesterol, 2.8 +/- 0.8 mmol/l; HDL cholesterol, 1.1 +/- 0.3 mmol/l; triglycerides, 1.4 mmol/l (median; range 0.5-7.1) were studied at baseline and on treatment. RESULTS: At baseline, dense LDLs were elevated (apolipoprotein [apo]B in LDL-5 plus LDL-6 >250 mg/l) in 63% of all patients. Sixteen weeks of treatment with pioglitazone did not significantly change triglycerides, total, LDL, and HDL cholesterol. However, pioglitazone reduced dense LDLs by 22% (P = 0.024). The mean diameter of LDL particles increased from 19.83 +/- 0.30 to 20.13 +/- 0.33 nm (P < 0.001 vs. placebo), whereas the mean LDL density decreased from 1.0384 +/- 0.0024 to 1.0371 +/- 0.0024 kg/l (P = 0.005 vs. placebo). The effect of pioglitazone on LDL size and density was independent of fasting triglycerides and HDL cholesterol at baseline and of changes in fasting triglycerides and HDL cholesterol. CONCLUSIONS: The prevalence of atherogenic dense LDL in nondiabetic, hypertensive patients is similar to patients with type 2 diabetes. Pioglitazone significantly reduces dense LDL independent from fasting triglycerides and HDL cholesterol. The antiatherogenic potential of pioglitazone may thus be greater than that expected from its effects on triglycerides, LDL, and HDL cholesterol alone.