Christel Joergensen

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 D3 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.

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, HbA1c, 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.

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, HbA1c, 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.

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.

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 analogue therapy, cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy: a randomized trial

To evaluate the effects of therapy with the vitamin D analogue paricalcitol on markers of cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy.

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

ObjectiveCentral 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 methodsIn 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. ResultsMeasurements 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. ConclusionIn 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.

Diabetes: Effect of vitamin D on diabetic kidney disease in T1DM

Low circulating levels of vitamin D metabolites were found to be associated with development of microalbuminuria in patients with type 1 diabetes mellitus from the DCCT/EDIC study. Could interventions aimed at improving vitamin D levels be a new option for the prevention of diabetic kidney disease?

Discrepancy Between Tonometric Ambulatory and Cuff-Based Office Blood Pressure Measurements in Patients With Type 1 Diabetes

J Clin Hypertens (Greenwich). 2012;14:686–693. ©2012 Wiley Periodicals, Inc.

VITAMIN D LEVELS AND MORTALITY IN TYPE 2 DIABETES: PP.17.143

Objective: To evaluate vitamin D as predictor of all-cause and cardiovascular mortality and risk of progression to micro- or macroalbuminuria in type 2 diabetic patients. Design and Methods: Prospective observational follow-up study. 289 type 2 diabetic patients followed for a median (range) of 15.5 (0.2–17.0) years. Mean (SD) age 54 (9) years, normoalbuminuria (n = 172), microalbuminuria (n = 73) and macroalbuminuria (n = 44) at baseline. Plasma 25(OH)D3 levels were determined by high performance liquid chromatography/tandem mass spectrometry on baseline samples. Severe vitamin D deficiency was defined as the lower 10% percentile (<13.9nmol/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 (eGFR), urinary albumin excretion rate (UAER) or HbA1c at baseline, but low levels were weakly associated with elevated systolic blood pressure (R = 0.13, p = 0.03). During follow-up, 141 (49%) patients died, 101 (35%) from cardiovascular causes. All-cause mortality was increased in patients with severe vitamin D deficiency (HR [95% CI] 2.03 [1.26–3.26], p < 0.01). The association persisted after adjustment for UAER, eGFR, HbA1c and conventional cardiovascular risk factors (HR 1.94 [1.19–3.16], p < 0.01). Furthermore severe vitamin D deficiency was associated with increased cardiovascular mortality (unadjusted HR 1.93 [1.1–3.39], p = 0.02; adjusted HR 1.49 [1.16–1.93], p < 0.01). 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 determined.