OBJECTIVE— To study the relationship of limited joint mobility(LJM) in type 1 diabetic patients with microvascular complications,hypertension, and early atherosclerosis and to determine whether sex has an influence on possible associations. RESEARCH DESIGN AND METHODS— A total of 335 consecutive unselected patients (191 women and 144 men), aged 14-40 years, were studied for LJM, retinopathy, nephropathy (stages III and IV), and hypertension. Standard laboratory tests were performed; the intima-media thickness (IMT) of the carotid arteries, which reflects the extent of early atherosclerosis, was measured by high-resolution ultrasound, and plaques were identified. RESULTS— The frequency of LJM was 33.7% (29.8% in women and 38.9% in men). Subjects with LJM had a longer diabetes duration (P< 0.001) than those without (women 16.7 ± 9.1 vs. 10.3 ± 6.0 years; men 15.0 ± 9.0 vs. 9.4 ± 6.3 years). Age,HbA1c, lipids, and systolic/diastolic blood pressure were not different between men and women with or without LJM. Men with LJM had a higher albumin excretion rate (37.1 vs. 13.1 μg/min, P < 0.05) than those without LJM and showed a higher risk of proteinuria (odds ratio 1.8, 95%CI 1.2-2.7; P < 0.05), retinopathy (2.4, 1.7-3.5; P <0.001), and hypertension (1.7, 1.2-2.6; P < 0.05). The occurrence of these complications was not different between women with and without LJM,but only women with LJM had a greater IMT (0.59 ± 0.13 vs. 0.55± 0.10 mm, P < 0.05) and a higher risk of plaques (odds ratio 2.1, 95% CI 1.3-3.4; P < 0.05) than women without LJM. In a multiple logistic regression analysis, adjusted for age and diabetes duration,male sex independently predicted the presence of LJM. Moreover, LJM proved to be an independent predictor of retinopathy in men only. CONCLUSIONS— LJM is an indicator of microvascular disease in men, and LJM is associated with early macrovascular disease in women.

To investigate associations between early atherosclerosis and possible risk factors for it in young patients with established Type 1 diabetes mellitus (DM), we measured the combined intima-media thickness (IMT) of the common carotid arteries with high resolution ultrasound in 310 young patients (age < or = 40 years, mean 27.9 +/- 6.5) with a diabetes duration > or = 2 years, and in two control groups of similar age (control 1:40 healthy subjects, control 2: 40 Type 1 DM recently diagnosed patients). Albumin excretion rate and lipids (total cholesterol and triglycerides) were measured and retinopathy and hypertension (systolic blood pressure > 140 or diastolic blood pressure > 90 mmHg) sought in the patients. Mean maximum IMT was 0.52 +/- 0.06 mm in control group 1 and 0.50 +/- 0.05 mm in control group 2 with a mean difference of 0.02 mm (95% CI: -0.01, 0.04). The more established Type 1 DM patients had a significantly greater IMT (0.57 +/- 0.13 mm, p < 0.001) than both control groups. In a subgroup analysis, patients with microvascular diabetic complications (n = 99) had a significantly greater IMT (0.63 +/- 0.17 vs 0.55 +/- 0.10 mm, p < 0.001) than those without (n = 211). In a multiple linear regression analysis with a significance level of < or = 0.10, the carotid artery IMT of our established diabetic patients was related to age, male gender, triglycerides and nephropathy, suggesting the latter as the main diabetes-specific risk for intima-media thickening in young Type 1 DM patients.

Our results suggest a relationship between the prevalence of hypertension and the deletion polymorphism of the ACE gene in young type 1 diabetic patients, but we could not find an association between carotid artery IMT and ACE genotype in this population.

Our results do not support the hypothesis that the ecNOS 4 a/b polymorphism interacts with the development of early carotid arteriosclerosis in young type-1 diabetic patients, but they give grounds to assume that in these patients it could influence the occurence of diabetic retinopathy.

The insertion/deletion (I/D) polymorphism of the angiotensin-converting-enzyme (ACE) gene has been reported to be associated with diabetic nephropathy in IDDM. We studied the relationship between this polymorphism and diabetic nephropathy in 210 IDDM patients. Their DNA was analyzed by polymerase chain reaction to type for the presence (I) or absence (D) of the 287 bp fragment in intron 16 of the ACE gene. The relative frequency of the different genotypes was 33.8% (DD), 43.8% (ID), and 22.4% (II). There were no significant differences between the genotypes in age, body-mass-index, blood pressure, plasma total cholesterol and triglycerides. The prevalence of microalbuminuria or nephropathy was 23.9% in the DD, 16.3% in the ID, and 17% in the II genotypes. The higher percentage of microalbuminuria or nephropathy in the DD genotypes was due to an increasing frequency of DD genotypes in the IDDM patients with long diabetes duration. After matching for diabetic retinopathy, gender, and diabetes duration, there was no association between the ACEI/D polymorphism and diabetic nephropathy. In conclusion, these results suggest that the ACE DD genotype cannot be regarded as a risk factor for diabetic nephropathy, but may even be associated with diabetes duration and thus longevity in IDDM patients.