OBJECTIVE -The aim of this study was to estimate the prevalence of the metabolic syndrome in Finnish type 1 diabetic patients and to assess whether it is associated with diabetic nephropathy or poor glycemic control.RESEARCH DESIGN AND METHODS -In all, 2,415 type 1 diabetic patients (51% men, mean age 37 years, duration of diabetes 22 years) participating in the nationwide, multicenter Finnish Diabetic Nephropathy (FinnDiane) study were included. Metabolic syndrome was defined according to the National Cholesterol Education Program diagnostic criteria. Patients were classified as having normal albumin excretion rate (AER) (n ϭ 1,261), microalbuminuria (n ϭ 326), macroalbuminuria (n ϭ 383), or end-stage renal disease (ESRD) (n ϭ 164). Glycemic control was classified as good (HbA 1c Ͻ7.5%), intermediate (7.5-9.0%), or poor (Ͼ9.0%). Creatinine clearance was estimated with the Cockcroft-Gault formula.RESULTS -The overall prevalence of metabolic syndrome was 38% in men and 40% in women. The prevalence was 28% in those with normal AER, 44% in microalbuminuric patients, 62% in macroalbuminuric patients, and 68% in patients with ESRD (P Ͻ 0.001). Patients with metabolic syndrome had a 3.75-fold odds ratio for diabetic nephropathy (95% CI 2.89 -4.85), and all of the separate components of the syndrome were independently associated with diabetic nephropathy. The prevalence of metabolic syndrome was 31% in patients with good glycemic control, 36% in patients with intermediate glycemic control, and 51% in patients with poor glycemic control (P Ͻ 0.001). Similarly, metabolic syndrome increased with worsening creatinine clearance.CONCLUSIONS -The metabolic syndrome is a frequent finding in type 1 diabetes and increases with advanced diabetic nephropathy and worse glycemic control.

Background: The milk casein-derived biologically active tripeptides, isoleucyl-prolyl-proline (Ile-Pro-Pro) and valyl-prolyl-proline (Val-Pro-Pro), have documented antihypertensive effect probably related to reduced angiotensin formation. It has been suggested that these tripeptides may reduce arterial stiffness and improve endothelial function. Our aim was to evaluate whether the milk-based drink containing Ile-Pro-Pro and Val-Pro-Pro influence arterial stiffness, measured as augmentation index (AIx), and endothelial function in man. Methods: In a double-blind parallel group intervention study, 89 hypertensive subjects received daily peptide milk containing a low dose of tripeptides (5 mg/day) for 12 weeks and a high dose (50 mg/day) for the following 12 weeks, or a placebo milk drink to titrate the dose-response effect. Arterial stiffness was assessed by pulse wave analysis at the beginning and end of each intervention period. Endothelial function was tested by examining pulse wave reflection response to sublingual nitroglycerin and salbutamol inhalation. Blood pressure was measured by using office and 24-h ambulatory blood pressure measurement. Results: At the end of the second intervention period, AIx decreased significantly in the peptide group compared with the placebo group (peptide group À1.53% (95% confidence interval (CI) À2.95 to À0.12), placebo group 1.20% (95% CI 0.09-2.32), P ¼ 0 Á 013). No change in endothelial function index was observed (peptide group 0.02 (95% CI À0.06 to 0.08), placebo group 0.04 (95% CI À0.04 to 0.12), P ¼ 0.85). There were no statistically significant differences between the effects of the peptide and placebo treatment on office and 24-h ambulatory blood pressure. Conclusions: Long-term treatment with Lactobacillus helveticus-fermented milk containing bioactive peptides reduces arterial stiffness expressed as AIx in hypertensive subjects.

on behalf of the Finnish Diabetic Nephropathy (FinnDiane) Study Group 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 background population. 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 Ͻ40 years but lower in those Ͼ45 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.

The finding of impaired vascular dilatation several years after a pre-eclamptic pregnancy could contribute to the higher risk of cardiovascular disease in these women.

This study demonstrates that pulse wave reflection and, thus, systemic arterial stiffness are increased in pregnant women with preeclampsia, but not in normotensive nonpregnant women with a history of preeclampsia. The results support the concept of generalized vascular dysfunction in preeclampsia.

Aims/hypothesis Augmentation index (AIx) and pulse wave velocity (PWV), both measures of arterial stiffness, constitute risk factors for cardiovascular disease. Notably, hyperglycaemia during an acute cardiovascular event is associated with poor prognosis. The objective of this study was to investigate whether acute hyperglycaemia increases arterial stiffness in patients with type 1 diabetes and in healthy subjects. Methods Twenty-two male patients with type 1 diabetes and thirteen healthy men, who were age-matched nonsmokers and without any diabetic complications, underwent a 120 min hyperglycaemic clamp (15 mmol/l). AIx was calculated to assess arterial stiffness. Before and during the clamp, carotid-radial (brachial) and carotid-femoral (aortic) PWV was measured. Results At baseline there was a difference in the AIx between patients with type 1 diabetes and healthy volunteers (−5±2.7 vs −20±2.8%, p<0.05). Acute hyperglycaemia rapidly increased AIx in patients with type 1 diabetes (−5±2.7 vs 8±2.5%, p<0.001) and healthy volunteers (−20±2.8 vs 6±8.8%, p<0.001). Brachial PWV increased during acute hyperglycaemia in patients with type 1 diabetes (7.1±1.2 vs 8.0±1.0 m/s, p<0.001), but not in healthy men (7.4±1.7 vs 7.3±1.4 m/s, NS). Conclusions/interpretation Acute hyperglycaemia increases the stiffness of intermediate-sized arteries and resistance arteries in young patients with type 1 diabetes and consequently emphasises the importance of strict daily glycaemic control. No change was observed in aortic PWV during the clamp, indicating that acute hyperglycaemia does not affect the large vessels.

GIANCARLO VIBERTI, MD, FRCP 4PER-HENRIK GROOP, MD, DMSC 2 OBJECTIVE -Dyslipidemia contributes to the progression of microvascular disease in diabetes. However, different lipid variables may be important at different stages of nephropathy. This study examines the pattern of dyslipidemia associated with the progression of nephropathy in patients with type 1 diabetes.RESEARCH DESIGN AND METHODS -A total of 152 patients with type 1 diabetes were recruited in order to represent various phases of nephropathy. Patients were followed for 8 -9 years, during which time they received standard care. Renal progression was defined a priori as a doubling in albumin excretion (in patients with normo-or microalbuminuria) or a decline in creatinine clearance (in those with macroalbuminuria). A panel of lipid variables was determined and correlated with indexes of progression.RESULTS -In patients with normoalbuminuria (n ϭ 66), progression was associated with male sex (P Ͻ 0.05), borderline albuminuria (P ϭ 0.02), and LDL-free cholesterol (P ϭ 0.02). In patients with microalbuminuria (n ϭ 51), progression was independently associated with triglyceride content of VLDL and intermediate-density lipoprotein (both P Ͻ 0.05). In patients with macroalbuminuria (n ϭ 36), a significant decline in the renal function (Ͼ3 ml ⅐ min Ϫ1 ⅐ year Ϫ1 ) was independently associated with poor glycemic control, hypertension, and LDL size (P Ͻ 0.05). When all patients with progressive nephropathy were analyzed together, only LDL cholesterol was predictive on multivariate analysis (P Ͻ 0.05), which masked the importance of triglyceride enrichment in microalbuminuria.CONCLUSIONS -Lipid variables are associated with progression of diabetic kidney disease, but the relationship is not the same at all stages. This finding has implications for the design of renoprotective strategies and the interpretation of clinical trials in type 1 diabetes. Diabetes Care 29:317-322, 2006T he control of blood lipids is one of the cornerstones in the treatment of type 1 diabetes. Apart from effects on macrovascular outcomes (1), dyslipidemia potentially contributes to microvascular disease (2,3). Prospective studies have confirmed a link between serum lipids and nephropathy (4 -10), although lipid fractions measured in these studies have been limited, and parameters associated with kidney disease have not been consistently identified (8,9). It remains to be established which lipids or lipoproteins are most important in the pathogenesis of nephropathy and should therefore be targeted for intervention. Furthermore, it may be that different lipid variables are important at different stages of diabetic kidney disease. For example, triglycerides and cholesterol appeared to have different effects on the progression of nephropathy, depending upon the duration of diabetes (10). Consequently, this study makes a detailed examination of the pattern of dyslipidemia associated with the progression of nephropathy, at each stage of renal disease, in patients with type 1 diabetes followed fo...

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