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Background. Diabetic nephropathy (DN) is a severe long-term complication of diabetes characterized by continuous albuminuria, a relentless decline in renal function, and an increased arterial blood pressure. Aims. Our aim was to find out if single nucleotide polymorphisms (SNPs) within the SLC22A1, SLC22A2, and SLC22A3 genes encoding organic cation transporters (OCTs) associate with DN or hypertension. Subjects and methods. We selected 90 SNPs (≈1 SNP/4 kb) in and surrounding SLC22A1, SLC22A2, and SLC22A3 using the HapMap data. The SNPs were tested for association with DN and hypertension in 1,086 unrelated Finnish patients with type 1 diabetes mellitus (T1DM). Eight of the SNPs were genotyped in 1,252 additional Finnish patients to verify the findings. Results. We detected nominal evidence of association ( P < 0.05) between the SLC22A2 (SNPs rs653753, rs596881, and rs316019) and SLC22A3 (SNPs rs376563, rs2048327, rs2457576, and rs1567438) genes and DN and hypertension in Finnish men with T1DM. We were not, however, able to replicate the associations, and none of them reached the significance limit adjusted for multiple testing ( P < 0.00009). Conclusions. There was no clear association between the SLC22A1, SLC22A2, and SLC22A3 genes and DN or hypertension. Although several SLC22A2 and SLC22A3 SNPs indicated association, lack of association was evident after the replication study. [ABSTRACT FROM AUTHOR]

In the general population, there is an inverse relationship between birth weight and adult systolic blood pressure. Because blood pressure in diabetic patients at least in part seems to be regulated by different mechanisms than in nondiabetic subjects, it is not known whether a similar correlation exists in diabetic individuals. Therefore, we obtained data on birth weight from original birth certificates in 1543 type 1 diabetic patients. Blood pressure was measured auscultatorily on a single occasion. In the 1225 patients born at term (after 37 weeks of gestation), the age- and sex-adjusted regression coefficients between systolic blood pressure and birth weight was -1.90 mm Hg/kg (95% confidence interval [CI], -3.71 to -0.09). The finding remained unchanged after adjustment for body mass index, current smoking, duration of diabetes, social class, antihypertensive therapy, glomerular filtration rate, glycemic control, and elevated albuminuria. The regression coefficient between birth weight and pulse pressure was of a similar magnitude. The age-adjusted regression coefficient between systolic blood pressure and birth weight seemed stronger in females (-3.34 mm Hg/kg; 95% CI, -6.06 to -0.62) than in males (-0.42 mm Hg/kg; 95% CI, -2.80 to 1.95), although this difference was not statistically significant. As a new finding, we report an inverse relationship between weight at birth and systolic blood pressure and pulse pressure in adult type 1 diabetic patients. Given the deleterious effects of elevated arterial blood pressure in diabetes, the impact of intrauterine growth retardation on the development of end-organ damage needs to be clarified.

Background: Pulse pressure (PP) increases with age as a result of arterial stiffening and is a powerful predictor of cardiovascular disease. Type 1 diabetes is associated with excessive cardiovascular mortality and increased arterial stiffness. We examined whether the age-related blood pressure changes in type 1 diabetic patients differ from those of the nondiabetic, Methods and Results: We performed a cross-sectional, case-control study of 2988 consecutively selected diabetic subjects and 5486 randomly selected nondiabetic control subjects. Blood pressure was measured twice by mercury sphygmomanometry on a single occasion. Compared with controls, diabetic subjects had a higher systolic blood pressure in all age groups, whereas diastolic blood pressure was higher in those <40 years but lower in those >45 years of age. Consequently, diabetic subjects had a higher PP and a higher prevalence of isolated systolic hypertension. The early age-related rise in PP was more pronounced in subjects with diabetic nephropathy but was also evident in diabetic subjects with normal albumin excretion rate. In a multiple regression analysis, PP in diabetic patients was associated with age, male sex, duration of diabetes, and albuminuria., Conclusions: A higher systolic pressure and an earlier decrease in diastolic pressure result in a higher and more rapidly increasing PP in type 1 diabetic patients. Our findings indicate accelerated arterial aging, which may contribute to the higher cardiovascular morbidity and mortality in these patients.