Gender,clamped hyperglycemia and arterial stiffness in patients with uncomplicated type 1 diabetes mellitus

Background: Diabetes mellitus (DM) reduces female gender-mediated protection against the development of renal disease possibly through effects on hyperglycemia. Women with DM also exhibit increased arterial stiffness, which may promote renal disease progression. The mechanisms responsible for increased arterial stiffness in women and the possible role of acute changes in ambient glycemia remain unknown.

Methods: Blood pressure, augmentation index (AIx), pulse wave velocity (PWV) and circulating mediators of the renin angiotensin system and nitric oxide (cGMP) were measured in men (n?=?22) and women (n?=?19) with uncomplicated type 1 DM under clamped euglycemic and hyperglycemic conditions.

Results: At baseline, men exhibited higher levels of angiotensin II (p?=?0.030) and lower cGMP levels (p?=?0.004), higher systolic blood pressure (124?±?2 versus 109?±?2?mmHg, p?p?p?p?p?=?0.853). In response to clamped hyperglycemia, systolic blood pressure increased in women (109?±?2 to 112?±?2?mmHg, p?=?0.005) but not men. Serum aldosterone increased and cGMP declined in women but not in men. Clamped hyperglycemia did not influence arterial stiffness in either group and radial and carotid AIx remained higher in women.

Conclusions: Arterial stiffness is higher in women with type 1 DM. This effect is not dependent on the effects of clamped hyperglycemia or neurohormonal activation.     

Serum 25-hydroxyvitamin D concentration and arterial stiffness among type 2 diabetes

Aim

To evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] and arterial stiffness in patients with type 2 diabetes.

Methods

Serum 25(OH)D was measured in a cross-sectional sample of 131 men and 174 women aged 30 years and over in Korea. Arterial stiffness was assessed by pulse wave velocity (PWV) obtained with a VP-2000 pulse wave unit. Fasting plasma glucose, insulin, lipid profile, HbA1c, calcium, phosphorous, and HS-CRP were measured.

Results

The prevalence of vitamin D deficiency was high (85.9%). Those with lower vitamin D levels had increased PWV. Using multivariate regression analysis, low 25(OH)D concentrations independently predicted PWV (p < 0.001) in people with type 2 diabetes after adjustment for other risk factors such as age, smoking, hypertension, HS-CRP, diabetes duration, hypertension duration, HbA1c, and BMI.

Conclusions

Vitamin D deficiency is common in type 2 diabetes, and a low 25(OH)D level is significantly associated with increased arterial stiffness in these patients. Vitamin D may influence the development of cardiovascular disease. Clinical intervention studies are needed to clarify whether treatment with vitamin D decreases the risk of cardiovascular disease in patients with type 2 diabetes.     

Maternal arterial stiffness in pregnancies affected by Type 1 diabetes mellitus

Aim There is little information about maternal central haemodynamics and arterial stiffness in pregnancies affected by Type 1 diabetes mellitus. The aim of the current study was to investigate whether maternal arterial stiffness is altered in pregnant women with Type 1 diabetes mellitus compared with women with uncomplicated pregnancies. Methods This was a cross‐sectional study involving 37 pregnant women without diabetes and 37 pregnant women with Type 1 diabetes mellitus during the second trimester of pregnancy. Maternal wave reflection (augmentation index) and pulse wave velocity of the carotid‐femoral and carotid‐radial part of the arterial tree were assessed non‐invasively using applanation tonometry. Results Pregnant women with normal pregnancies and Type 1 diabetes mellitus had similar augmentation index (3.7 ± 12.8 vs. 5.1 ± 12.6%, P = 0.6), even after adjusting for possible confounders. Within the group of diabetic women, augmentation index was associated with duration of diabetes (P = 0.003, r² = 0.22) but not with glycated haemoglobin. Pulse wave velocities were similar between the two groups of women (carotid‐femoral: 5.6 ± 0.9 vs. 5.7 ± 1.1 m/s, P = 0.4; carotid‐radial: 7.4 ± 1.2 vs. 7.8 ± 1 m/s, P = 0.1). In the diabetic women there was no significant association between the pulse wave velocities and either duration of diabetes or glycated haemoglobin. Conclusions Pregnancy in women with Type 1 diabetes mellitus is not associated with altered maternal systemic arterial stiffness. However, maternal wave reflections increase with the duration of diabetes.     

Lower intake of saturated fatty acids is associated with persistently higher arterial stiffness in patients with type 2 diabetes

Aims/IntroductionThere are few studies to investigate the relationship between macronutrients and longitudinal changes in arterial stiffness in patients with type 2 diabetes mellitus. This exploratory study sought to determine whether macronutrients were correlated with increased arterial stiffness independently of conventional atherosclerotic risk factors.Materials and MethodsThe study participants comprised 733 type 2 diabetes outpatients who had no apparent history of cardiovascular diseases. The dietary schedule was assessed with a validated, brief, self‐administered diet history questionnaire. At baseline and at years 2 and 5, brachial‐ankle pulse wave velocity was measured. A multivariable linear mixed‐effects model was used to determine the predictive values of macronutrients and atherosclerotic risk factors for longitudinal changes in brachial‐ankle pulse wave velocity.ResultsThere was a significant increase in brachial‐ankle pulse wave velocity values over the 5‐year follow‐up period. In a multivariable linear mixed‐effects model that adjusted for age and sex, lower saturated fatty acid intake was significantly correlated with persistently higher brachial‐ankle pulse wave velocity, independently of other atherosclerotic risk factors. Lower intake of dairy products in particular showed this correlation.ConclusionsOur data showed that lower saturated fatty acids intake was correlated with persistently higher brachial‐ankle pulse wave velocity in type 2 diabetes patients. Among food sources of saturated fatty acids, lower dairy products specifically were correlated with elevated brachial‐ankle pulse wave velocity. This might be because the consumption of dairy products in Japan is much lower than in Western countries.     

Acute hyperglycaemia rapidly increases arterial stiffness in young patients with type 1 diabetes

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 non-smokers 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. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Long-term pioglitazone therapy improves arterial stiffness in patients with type 2 diabetes mellitus

Pioglitazone, a peroxisome proliferator-activated receptor γ agonist, not only improves insulin resistance and glycemic control, but may also have additional beneficial vascular effects in patients with type 2 diabetes mellitus. We investigated whether pioglitazone had an influence on arterial stiffness, which is an independent predictor of cardiovascular events, in 204 patients with type 2 diabetes mellitus. A prospective, nonrandomized, open-label trial was performed that involved 41 patients treated with pioglitazone, 46 patients receiving sulfonylureas, 67 patients on insulin, and 50 patients on diet/exercise only. The follow-up period was 56 ± 3 months. Arterial stiffness was evaluated by using the arterial stiffness index (ASI), which was based on analysis of the pulse wave amplitude pattern obtained during automated blood pressure measurement in the upper limb. The 4 groups had a similar baseline ASI, which was greater than the reference range in each group. Although antidiabetic therapies improved hemoglobin A_1c and low-density lipoprotein cholesterol, ASI only decreased significantly in the pioglitazone group. Thus, pioglitazone improved abnormal arterial stiffness in patients with type 2 diabetes mellitus via a mechanism beyond the metabolic improvement. These findings may have important clinical implications in the use of pioglitazone in patients with type 2 diabetes mellitus.     

The association of diabetes mellitus with carotid atherosclerosis and arterial stiffness in the Corinthia study

Background and aimsEvaluation of arterial stiffness and carotid atherosclerotic burden can provide important prognostic information regarding the risk of future cardiovascular events. The aim of this study was to assess these vascular properties in patients with diabetes mellitus (DM).Methods and resultsIn the context of the observational “Corinthia” study, we analyzed 1757 participants with determined DM status. Carotid ultrasonography was performed to evaluate intima-media thickness (cIMT) and carotid plaque burden. Arterial stiffness was estimated via assessment of carotid-to-femoral pulse wave velocity (cfPWV). Individuals with DM had increased mean cIMT, maximum cIMT, carotid plaque burden, and cfPWV compared to those without DM. After multivariable regression analysis, the presence of DM was still associated with significantly increased mean cIMT (by 0.074 mm, p = .004), maximum cIMT (by 0.134 mm, p = .007), cfPWV (by 0.929 m/s, p < .001), and a higher prevalence of carotid plaques (odds ratio 1.52, 95% confidence intervals 1.11, 2.10, p = .01). In a propensity score-matched cohort, mean cIMT, maximum cIMT, and carotid plaque burden were significantly higher in individuals with DM. Analysis according to territory of cIMT measurement displayed substantial differences in left (DM: 1.32 ± 0.78 mm vs. no DM: 1.20 ± 0.66 mm, p = .04) and right carotid bulbs (DM: 1.33 ± 0.82 mm vs. no DM: 1.18 ± 0.69 mm, p = .02) with respect to DM status while non-significant variations were observed in left (DM: 0.98 ± 0.49 mm vs. no DM: 0.91 ± 0.35 mm, p = .06) and right common carotid artery (DM: 0.95 ± 0.50 mm vs. no DM: 0.92 ± 0.40 mm, p = .36).ConclusionsDiabetes mellitus is associated with increased cfPWV and cIMT, with more pronounced lesions in the carotid bulb.     

Decreased heart rate variability in patients with type 1 diabetes mellitus is related to arterial wall stiffness

OBJECTIVE: Low heart rate variability (HRV) is, in several patient groups, related to poor prognosis. The underlying mechanisms are still unclear. The aim was to study if there is a relationship between HRV, which is a measure of baroreceptor function, and atherosclerosis. DESIGN: The relationship between heart rate variability and carotid arterial wall stiffness was studied in subjects with type 1 diabetes mellitus in which autonomic dysfunction and early atherosclerosis are common. HRV was assessed from power spectral analysis of 24-h Holter recordings and arterial wall stiffness was assessed from an ultrasound study of the right common carotid artery. SETTING: A university hospital. SUBJECTS: Fifty-nine patients (41 +/- 8 years) from the Stockholm Diabetes Intervention Study (SDIS) were investigated. These patients were randomized to intensified conventional treatment or standard treatment approximately 12 years before this study. RESULTS: Patients with stiffer arteries had lower HRV in all spectral bands (r = -0.32 to -0.40, P = 0.06-0.001). This relation remained on correcting for age. All spectral parameters of HRV correlated with the mean HbA1c from 10 years of study (r = -0.37 to -0.40, P = 0.004-0.001). CONCLUSIONS: In patients with type 1 diabetes mellitus, heart rate variability and arterial wall stiffness are related to each other. The results suggests that the autonomic nervous system could be a link between diabetes and vascular disease.     

Effect of atorvastatin on regional arterial stiffness in patients with type 2 diabetes mellitus

OBJECTIVE: A statin, a potent lipid-lowering drug, improves pain-free walking distance in patients with peripheral arterial disease (PAD) without increasing the ankle-brachial pressure index (ABI). Arterial stiffness affects the blood flow of peripheral arteries. The purpose of this study was to evaluate the effect of cholesterol-lowering with atorvastatin on regional arterial stiffness in patients with type 2 diabetes mellitus. METHODS: The subjects were 22 type 2 diabetic patients with hypercholesterolemia, who received atorvastatin at a daily dose of 10 mg for 6 months. Before and after the treatment with atorvastatin, we measured pulse wave velocity (PWV) in the heart-brachial, heart-carotid, heart-femoral and femoral-ankle segments. RESULTS: Following treatment with atorvastatin, femoral-ankle PWV showed a significant reduction. The PWV of other arterial segments tended to decrease, although the changes were not statistically significant. We found no significant changes in blood pressure, heart rate, ABI, or plasma concentrations of glucose, L-arginine and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial function. CONCLUSIONS: Atorvastatin treatment was associated with an improvement in the stiffness of leg arteries in type 2 diabetes mellitus. This may partly explain the statin-mediated improvement of walking performance in those with PAD.     

Carotid stiffness and microalbuminuria in patients with type 2 diabetes

Microalbuminuria is associated with higher cardiovascular mortality, especially in diabetics. But the direct association between microalbuminuria and vascular wall properties is still not clear. We investigated quantitative carotid stiffness (QCS) index in relation to microalbuminuria in 260 Chinese diabetic patients. In categorical analyses, patients with elevated urinary albumin-to-creatinine ratio (uACR) had higher QCS than those with normal uACR (P < 0.001). The corresponding values for QCS values were 4.4 and 5.9, respectively. In multiple stepwise regression analyses, QCS was significantly associated with age, uACR, plasma glycosylated hemoglobin A_1C (HbA_1C), and current smoking (P < 0.05 for all). In conclusion, carotid stiffness as measured by QCS, a local functional measurement of the arterial wall, is increased in type 2 diabetes with microalbuminuria. Wei-Wei Zhan and Yu-Hong Chen have contributed equally to this article.     

Carotid intima-media thickness and stiffness in relation to type 2 diabetes in Chinese

We investigated carotid intima-media thickness (IMT) and quantitative carotid stiffness (QCS) index in relation to plasma glycosylated hemoglobin A_1C (HbA_1C) and duration of diabetes mellitus in 337 Chinese diabetic patients. In categorical analyses, carotid IMT was 710 μm in subjects with a duration of diabetes mellitus ≤2 years, 760 μm in subjects with a duration of diabetes mellitus more than two years and with plasma HbA_1C < 6.5% (P < 0.05), and 790 μm in subjects with a duration of diabetes mellitus more than two years but with plasma HbA_1C ≥ 6.5% (P < 0.01). The corresponding values for QCS values were 4.5, 4.6 and 5.1 (P < 0.05), respectively. In multiple stepwise regression analyses carotid IMT was significantly associated with the duration of diabetes mellitus, systolic blood pressure and serum concentration of total cholesterol, whereas QCS was significantly associated with age, HbA_1C, systolic and diastolic blood pressure (P < 0.05). In conclusion, carotid IMT as a structural measure of arterial wall is increased in patients with a longer history of diabetes mellitus, whereas QCS as functional index is mainly influenced by the quality of blood glucose control.     

老年2型糖尿病患者糖化血红蛋白与动脉僵硬度的关系

目的探讨老年2型糖尿病患者不同糖化血红蛋白(HbA1c)与动脉僵硬度的关系。方法选择老年2型糖尿病患者108例,根据年龄分为60～69岁组39例,70～79岁组39例,80～89岁组30例。以HbA1c作为评分标准:分为血糖控制不佳患者56例和血糖控制良好患者52例。以颈动脉-股动脉脉搏波传导速度(cfPWV)作为评价动脉僵硬度指标,进行cfPWV及下肢动脉多普勒超声、血脂检测,并进行相关因素分析。结果 60～69岁组、70～79岁组、80～89岁组血糖控制不佳患者cfPWV、LDL-C、TG水平明显高于血糖控制良好患者,差异有统计学意义(P<0.05,P<0.01)。回归分析显示,cfPWV与HbA1c、甘油三酯呈正相关(r=0.652,r=0.425,P=0.000)。结论血糖控制不佳是老年2型糖尿病患者动脉僵硬度增加的重要危险因素。     

Prevalence of arterial stiffness in adolescents with type 2 diabetes in the TODAY cohort: Relationships to glycemic control and other risk factors

Aims

We aimed to determine the prevalence of arterial stiffness in young adults with youth-onset type 2 diabetes who previously participated in the TODAY clinical trial and whether arterial stiffness is influenced by their prior diabetes treatment assignment or glycemic control.

Helicobacter pylori infection and arterial stiffness in patients with type 2 diabetes mellitus

Epidemiologic studies have suggested possible atherogenic roles for such pathogens as Chlamydia pneumoniae, Helicobacter pylori (Hp), cytomegalovirus, and herpes simplex virus. The aim of the present study was to examine the relationship between seropositivity of antibodies to Hp (Hp infection) and arterial stiffness determined by pulse wave velocity (PWV) in 130 patients (73 men and 57 women) with type 2 diabetes mellitus without a history of cardiovascular disease. The prevalence of Hp infection in patients with type 2 diabetes mellitus was 53.8%. Age (66.7 ± 11.3 vs 60.0 ± 12.2 years, P = .0014) and systolic blood pressure (138 ± 19 vs 131 ± 22 mm Hg, P = .0420) were significantly higher in patients with Hp infection than in those without. Serum C-reactive protein was higher in patients with Hp infection than in those without, although it did not reach statistical significance (0.23 ± 0.27 vs 0.18 ± 0.20 mg/dL, P = .2205). Pulse wave velocity was significantly higher in patients with Hp infection than in those without (1877 ± 550 vs 1585 ± 331 cm/s, P = .0005). Multiple regression analysis demonstrated that age (β = .388, P < .0001), mean arterial pressure (β = .289, P = .0006), hypertensive treatment (β = .185, P = .0282), and presence of Hp infection (β = .169, P = .0220) were independent determinants of PWV. In conclusion, Hp infection is associated with arterial stiffness determined by PWV in patients with type 2 diabetes mellitus.     

Association between bone metabolism regulators and arterial stiffness in type 2 diabetes patients

Background and Aim

Osteopontin (OPN), osteonectin (ON) and osteocalcin (OC) play an important role in the development of vascular calcifications, but it is unclear whether these bone metabolism regulators contribute to the development of arterial stiffness in type 2 diabetes patients. We therefore aim to determine the relationship between plasma concentrations of OPN, ON, OC and arterial stiffness in type 2 diabetes patients.

Angiotensin II type 1 receptor blockers prevent aortic arterial stiffness in elderly patients with hypertension

Backgrounds and aims: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blockers (ARBs) are potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of ARBs in aged patients with essential hypertension are not entirely investigated.

Methods: The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension.

Results: In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared to patients without essential hypertension. In correlation analysis, PWV was associated positively with age, hypertension duration, and carotid atherosclerosis. However, there was no relationship between PWV and gender in aged patients with essential hypertension. In a perspective study, 6–12 months administration of ARBs (losartan, 50 mg/day; telmisartan, 40 mg/day; valsartan 80 mg/day; irbesartan, 150 mg/day) remarkably reduced PWV in aged patients with essential hypertension. Regression analyses of multiple factors indicated that the effects of ARBs on arterial stiffness were not associated with the reduction of blood pressure.

Conclusion: ARB treatment is a negative risk factor of arterial stiffness in aged patients with essential hypertension.     

Regional arterial stiffness associated with ischemic heart disease in type 2 diabetes mellitus

Arterial stiffness is increased in type 2 diabetes mellitus, and diabetes preferentially affects arterial stiffness of the central (elastic, capacitive) over peripheral (muscular, conduit) arteries. We hypothesized that arterial stiffness of the central artery may be more closely associated with ischemic heart disease (IHD) than stiffness of peripheral arteries in type 2 diabetes mellitus. The subjects were 595 type 2 diabetes patients including 70 with IHD. Arterial stiffness was measured as pulse wave velocity (PWV) in the heart-carotid, heart-femoral, heart-brachial, and femoral-ankle regions. The PWV values of the four segments correlated with each other in patients without IHD. However, the correlations were less impressive in those with IHD, suggesting unequal stiffening of regional arteries in IHD. As compared with patients without IHD, the IHD group showed significantly higher PWV values of the four arterial segments, particularly of the heart-femoral region. The presence of IHD was significantly associated with higher heart-femoral PWV, and this association remained significant and independent of other factors in a multiple logistic regression analysis. Pulse pressure was more strongly correlated with PWV of the heart-femoral than other arterial regions. Thus, diabetic patients with IHD have increased stiffness of arteries, particularly of the aorta, supporting the concept that central arterial stiffness plays an important role in the development of IHD.