24-hour central aortic systolic pressure and 24-hour central pulse pressure are related to diabetic complications in type 1 diabetes - a cross-sectional study.

BACKGROUND: Non-invasive measurements of 24 hour ambulatory central aortic systolic pressure (24 h-CASP) and central pulse pressure (24 h-CPP) are now feasible. We evaluate the relationship between 24 h central blood pressure and diabetes-related complications in patients with type 1 diabetes. METHODS: The study was cross-sectional, including 715 subjects: 86 controls (C), 69 patients with short diabetes duration (< 10 years), normoalbuminuria (< 30 mg/24 h) without receiving antihypertensive treatment (SN), 211 with longstanding diabetes (≥ 10 years) and normoalbuminuria (LN), 163 with microalbuminuria (30-299 mg/24 h) (Mi) and 186 with macroalbuminuria (> 300 mg/24 h) (Ma).24 h-CASP and 24 h-CPP was measured using a tonometric wrist-watch-like device (BPro, HealthStats, Singapore) and derived using N-point moving average. RESULTS: In C, SN, LN, Mi and Ma mean ± SD 24 h-CASP was: 114 ± 17, 115 ± 13, 121 ± 13, 119 ± 16 and 121 ± 13 mmHg (p < 0.001); and 24 h-CPP: 38 ± 8, 38 ± 7, 44 ± 10, 46 ± 11 and 46 ± 11 mmHg, (p < 0.001).Following rigorous adjustment (24 h mean arterial pressure and conventional risk factors), 24 h-CASP and 24 h-CPP increased with diabetes, albuminuria degree, previous cardiovascular disease (CVD), retinopathy and autonomic dysfunction (p ≤ 0.031).Odds ratios per 1 standard deviation increase in 24 h-CASP, 24 h-CPP and 24 h systolic blood pressure (24 h-SBP) were for CVD: 3.19 (1.68-6.05), 1.43 (1.01-2.02) and 2.39 (1.32-4.33), retinopathy: 4.41 (2.03-9.57), 1.77 (1.17-2.68) and 3.72 (1.85-7.47) and autonomic dysfunction: 3.25 (1.65-6.41), 1.64 (1.12-2.39) and 2.89 (1.54-5.42). CONCLUSIONS: 24 h-CASP and 24 h-CPP was higher in patients vs. controls and increased with diabetic complications independently of covariates. Furthermore, 24 h-CASP was stronger associated to complications than 24 h-SBP.The prognostic significance of 24 h-CASP and 24 h-CPP needs to be determined in follow-up studies. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT01171248.

Tonometric devices for central aortic systolic pressure measurements in patients with type 1 diabetes: comparison of the BPro and SphygmoCor devices.

OBJECTIVE: Central blood pressure may be a better risk marker than brachial blood pressure and can be measured noninvasively by tonometric devices. We investigate whether tonometric measurements are feasible in patients with diabetes and whether the degree of albuminuria or increased arterial stiffness affects measurements. PATIENTS AND METHODS: In 676 patients with type 1 diabetes, comparison of central aortic systolic pressure (CASP) measurements by the BPro and the SphygmoCor devices were made. The BPro device can obtain both office and 24-h measurements, whereas the SphygmoCor device is an accepted device for CASP measurements. RESULTS: Measurements of CASP with both BPro and SphygmoCor were available in 598 (88.5%) patients (mean age 54 years; mean diabetes duration 33 years; 45.2% women), and mean±SD of CASP was 122±17 and 118±17 mmHg, respectively (P<0.001). Linear and intraclass correlation coefficients between CASP estimated from BPro and SphygmoCor were r equal to 0.96 and 0.95 (P<0.001 for both). The mean±SD difference between devices was 3.6±4.8 mmHg (P<0.001).Analyses according to the level of albuminuria or degree of arterial stiffness were confirmatory. CONCLUSION: In patients with type 1 diabetes, tonometric measurements of CASP with BPro and SphygmoCor showed strong correlations, although values differed by ∼4 mmHg between devices. Level of CASP, arterial stiffness, and degree of albuminuria did not interfere with the agreement between devices.In addition, the BPro device can obtain 24-h measurements and may thus be useful to assess the diurnal patterns of CASP.

Arterial stiffness is associated with cardiovascular, renal, retinal, and autonomic disease in type 1 diabetes.

OBJECTIVE: In patients with type 1 diabetes, we investigated the association between arterial stiffness and diabetes complications. RESEARCH DESIGN AND METHODS: This was a cross-sectional study including 676 Caucasian patients with type 1 diabetes (374 [55%] men, aged 54 ± 13 years [mean ± SD]) and 51 nondiabetic controls (28 [55%] men, aged 47 ± 13 years). Aortic pulse wave velocity (PWV) was measured with SphygmoCor (AtCor Medical, Sydney, Australia) for 635 patients and all 51 controls. RESULTS: PWVs (mean ± SD) in patients and controls were 10.4 ± 3.4 and 7.6 ± 1.9 m/s, respectively (P < 0.001). After multivariate adjustment, PWV correlated with age, diabetes duration, urinary albumin excretion rate, heart rate, and blood pressure (P < 0.05 for all). ANCOVA was used for comparisons between groups and adjusted for gender, age, estimated glomerular filtration rate, heart rate, HbA(1c), and 24-h mean arterial pressure. PWVs in normoalbuminuric, microalbuminuric, and macroalbuminuric patients were 9.5 ± 3.2, 11.0 ± 3.6, and 11.4 ± 3.0 m/s, respectively (adjusted P < 0.001). PWV in patients with previous cardiovascular disease, versus patients without, was 12.1 ± 3.5 vs. 10.0 ± 3.2 m/s, respectively (adjusted P < 0.001). PWVs in patients with high (≥140/90 mmHg) versus intermediate (130-40/80-89 mmHg) and low (<130/80 mmHg) blood pressure were 11.8 ± 3.6, 10.0 ± 3.0, and 9.8 ± 3.3 m/s, respectively (adjusted P < 0.001). Furthermore, PWV increased with increasing degree of retinopathy: 8.0 ± 2.5 m/s (nil), 10.0 ± 2.8 m/s (simplex), 12.1 ± 3.5 m/s (proliferative), and 12.7 ± 2.4 m/s (blind), respectively (adjusted P < 0.001). Finally, PWV increased with abnormal heart rate variability: 11.5 ± 3.3 m/s vs. 10.1 ± 3.1 m/s (borderline) and 8.1 ± 2.1 m/s (normal) (adjusted P = 0.027). CONCLUSIONS: Arterial stiffness increased with presence and duration of type 1 diabetes. Furthermore, PWV increased with all the investigated diabetes complications (cardiovascular, renal, retinal, and autonomic disease) independently of other risk factors.

Discrepancy between tonometric ambulatory and cuff-based office blood pressure measurements in patients with type 1 diabetes.

The aim of the current study was to compare ambulatory blood pressure (ABP) with office blood pressure (OBP) in diagnosing hypertension (HTN) in type 1 diabetes. The cross-sectional study included 569 type 1 diabetes patients, with a mean ± standard deviation (SD) age of 55 ± 13 years and diabetes duration of 33 ± 16 years, and 315 (55%) men. Blood pressure ≥ 130/80 mm Hg defined HTN. ABP was measured by tonometry and OBP by sphygmomanometry. Elevated ABP with normal OBP defined masked uncontrolled HTN, and normal ABP with elevated OBP defined isolated uncontrolled clinic HTN. Mean ± SD 24-hour ABP, daytime ABP, and OBP was 128 ± 16/75 ± 10 mm Hg, 133 ± 16/77 ± 11 mm Hg, and 136 ± 14/76 ± 8 mm Hg, respectively (P<.001). With 24-hour and daytime ABP, HTN was present in 256 (45%) and 304 (53%) patients; normal BP in 102 (18%) and 88 (15%) patients; isolated uncontrolled clinic HTN in 154 (27%) and 104 (%) patients; and masked uncontrolled HTN in 57 (10%) and 73 (13%) patients. Twenty-four-hour ABP and OBP showed disagreement in diagnosing HTN in 211 (37%) patients. Daytime ABP and OBP disagreed in 177 (31%) patients. HTN by 24-hour and daytime ABP was present in 313 (55%) and 377 (66%) patients. ABP measurements were well-tolerated and successful in 98%. A total of 92% would volunteer for repeat measurements and 83% preferred the tonometry to conventional cuff-based devices. In patients with type 1 diabetes, tonometric ABP measurements are feasible. ABP and OBP disagree in diagnosing HTN in 31% to 37% of patients. Furthermore, 55% to 66% of patients do not reach target BP of <130/80 mm Hg despite regular follow-up.

Ambulatory tonometric blood pressure measurements in patients with diabetes.

BACKGROUND: Arterial tonometry is a novel technique for measuring ambulatory blood pressure (AMBP). The watch-like device BPro(®) (HealthSTATS International, Singapore) captures radial pulsewave reflection and calculates brachial blood pressure (BP). In this study we investigate if arterial tonometry is applicable and reliable in patients with diabetes. SUBJECTS AND METHODS: We compared tonometric (BPro) to cuff-based oscillometric and auscultatoric BPs (Takeda model TM2421, A&D Medical, Tokyo, Japan) in 25 Caucasian patients with type 1 or type 2 diabetes. Patients were seen twice within 2 weeks. At visit 1, a 15-min rest was followed by the recording of three cuff-based BPs and 2-min continuous tonometric BPs. At both visits 24-h AMBP measurements were recorded with the BPro device. RESULTS: At Visit 1, auscultatoric BP (mean±SD) was 136±19/72±8 mm Hg versus 138±19/78±8 mm Hg with the tonometric device. Visit 1 AMBP was 131±20/76±9 mm Hg versus 131±12/75±9 mm Hg at Visit 2. Mean 24-h AMBP, daytime BP, nighttime BP, and dipping at the two visits were similar (P>0.40). Linear and intraclass correlations coefficients between auscultatoric and tonometric systolic and diastolic BP were r=0.86 and 0.65, respectively (P<0.001 for both), and r=0.83 and 0.77, respectively (P<0.001 for both). The mean differences between devices were 1.9±10 and 5.5±6.6 mm Hg for systolic and diastolic BP, respectively. CONCLUSIONS: In patients with diabetes tonometric and cuff-based BPs are comparable, and tonometric AMBPs are reproducible and feasible.

Vitamin D levels and asymptomatic coronary artery disease in type 2 diabetic patients with elevated urinary albumin excretion rate.

OBJECTIVE: Coronary artery disease (CAD) is the major cause of morbidity and mortality in type 2 diabetic patients. Severe vitamin D deficiency has been shown to predict cardiovascular mortality in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We investigated the association among severe vitamin D deficiency, coronary calcium score (CCS), and asymptomatic CAD in type 2 diabetic patients with elevated urinary albumin excretion rate (UAER) >30 mg/24 h. This was a cross-sectional study including 200 type 2 diabetic patients without a history of CAD. Severe vitamin D deficiency was defined as plasma 25-hydroxyvitamin D (p-25[OH]D3) <12.5 nmol/L. Patients with plasma N-terminal pro-brain natriuretic peptide >45.2 ng/L or CCS ≥400 were stratified as being high risk for CAD (n= 133). High-risk patients were examined by myocardial perfusion imaging (MPI; n = 109), computed tomography angiography (n = 20), or coronary angiography (CAG; n = 86). Patients' p-25(OH)D3 levels were determined by high-performance liquid chromatography/tandem mass spectrometry. RESULTS: The median (range) vitamin D level was 36.9 (3.8-118.6) nmol/L. The prevalence of severe vitamin D deficiency was 9.5% (19/200). MPI or CAG demonstrated significant CAD in 70 patients (35%). The prevalence of CCS ≥400 was 34% (68/200). Severe vitamin D deficiency was associated with CCS ≥400 (odds ratio [OR] 4.3, 95% CI [1.5-12.1], P = 0.005). This association persisted after adjusting for risk factors (4.6, 1.5-13.9, P = 0.007). Furthermore, severe vitamin D deficiency was associated with asymptomatic CAD (adjusted OR 2.9, 1.02-7.66, P = 0.047). CONCLUSIONS: In high-risk type 2 diabetic patients with elevated UAER, low levels of vitamin D are associated with asymptomatic CAD.

Vitamin D levels, microvascular complications, and mortality in type 1 diabetes.

OBJECTIVE: To evaluate vitamin D as a predictor of all-cause mortality, progression from normoalbuminuria to micro- or macroalbuminuria, and the development of background or proliferative retinopathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A prospective observational follow-up study in which an inception cohort of type 1 diabetic patients was followed from onset of diabetes diagnosed between 1979 and 1984. Plasma vitamin D [25(OH)D3] levels were determined by high performance liquid chromatography/tandem mass spectrometry in 227 patients before the patients developed microalbuminuria. Values equal to or below the 10% percentile (15.5 nmol/L) were considered severe vitamin D deficiency. RESULTS: Median (range) vitamin D was 44.6 (1.7-161.7) nmol/L. Vitamin D level was not associated with age, sex, urinary albumin excretion rate (UAER), or blood pressure. During follow-up, 44 (18%) patients died. In a Cox proportional hazards model, the hazard ratio for mortality in subjects with severe vitamin D deficiency was 2.7 (1.1-6.7), P = 0.03, after adjustment for UAER, HbA(1c), and conventional cardiovascular risk factors (age, sex, blood pressure, cholesterol, smoking). Of the 220 patients, 81 (37%) developed microalbuminuria and 27 (12%) of these progressed to macroalbuminuria. Furthermore, 192 (87%) patients developed background retinopathy, whereas 34 (15%) progressed to proliferative retinopathy. Severe vitamin D deficiency at baseline did not predict the development of these microvascular complications. CONCLUSIONS: In patients with type 1 diabetes, severe vitamin D deficiency independently predicts all-cause mortality but not development of microvascular complications in the eye and kidney. Whether vitamin D substitution in type 1 diabetic patients can improve the prognosis remains to be investigated.

Vitamin D levels and mortality in type 2 diabetes.

OBJECTIVE: To evaluate vitamin D as a predictor of all-cause and cardiovascular mortality and risk of progression to micro- or macroalbuminuria in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In a longitudinal observational follow-up study, 289 type 2 diabetic patients with normoalbuminuria (n = 172), microalbuminuria (n = 73), and macroalbuminuria (n = 44) at baseline were followed for a median (range) of 15.0 (0.2-23) years. Mean ± SD age was 54 ± 9 years. Plasma 25-hydroxyvitamin D(3) levels were determined by high-performance liquid chromatography/tandem mass spectrometry on baseline samples. Severe vitamin D deficiency was defined as the lower 10th percentile (<13.9 nmol/l). RESULTS: Median (range) vitamin D level was 35.7 (5-136.7) nmol/l. Vitamin D levels were not associated with age, sex, estimated glomerular filtration rate, urinary albumin excretion rate (UAER), or A1C at baseline, but low levels were weakly associated with elevated systolic blood pressure (R = 0.13, P = 0.03). During follow-up, 196 (68%) patients died. All-cause mortality was increased in patients with severe vitamin D deficiency (hazard ratio 1.96 [95% CI 1.29-2.98]). The association persisted after adjustment for UAER, A1C, diabetes duration, and conventional cardiovascular risk factors (2.03 [1.31-3.13]). Severe vitamin D deficiency was associated with increased cardiovascular mortality (1.95 [1.11-3.44]), and the association persisted after adjustment (1.90 [1.15-3.10]). Severe vitamin D deficiency at baseline did not predict progression to micro- or macroalbuminuria. CONCLUSIONS: In type 2 diabetic patients, severe vitamin D deficiency predicts increased risk of all-cause and cardiovascular mortality, independent of UAER and conventional cardiovascular risk factors. Whether vitamin D substitution improves prognosis remains to be investigated.