Calcification In Subjects Research Articles

Sella turcica bridging and ponticulus posticus calcification in subjects with different dental anomalies

This study aimed to evaluate and compare the bridging and dimensions of the sella turcica and calcification of the ponticulus posticus in subjects with different dental anomalies. Pretreatment recordsof orthodontic patients with palatally impacted canines (n=95), mandibular second premolar agenesis (n=45), maxillary lateral incisor agenesis (n=75), tooth transpositions (TT, n=25), peg-shaped maxillary lateral incisors (n=30), and third molar agenesis (TMA, n=145) were analyzed and compared with the control group (CG) consisting of 145 subjects with skeletal Class I malocclusion and no dental anomalies. The length, diameter, and depth of the sella turcica were calculated for each patient. The degree of sella turcica bridging was scored as type I, II, and III, whereas the extent of ponticulus posticus was classified as Class I, II, and III. Only decreases in the length and diameter of the sella turcica in subjects with TT were found to be statistically significant. Although type II bridging frequency was found to be significantly lower in subjects with mandibular second premolar agenesis, maxillary lateral incisor agenesis, TT, and TMA, type III bridging frequency was found to be significantly higher only in subjects with TMA. The decrease in Class I calcificationfrequencies and the increase in Class II calcification frequencies were found to be significant in subjects with palatally impacted canines, TT, and TMA compared with the CG. In addition, the presence of Class III calcification was found to be significantly more frequent in subjects with TMA than in the CG. Although type II and type III bridging frequencies were found to be higher than in previous studies because of the higher type II bridging frequency in the CG, type II bridging frequency was found to be insignificant. Furthermore, an increased frequency of ponticulus posticus calcification was observed in subjects with palatally impacted canines, TT, and TMA.

Would acetazolamide inhibit progression of atheromatous vascular calcification?

Vascular calcification is a recognised source of morbidity among mid-age and elderly subjects. Its development follows classical mineralisation pathways, inhibited by acidosis. It is known that the final mechanism of tissue mineralization involves three processes, all of which are highly pH dependent. Calcium interacts with phosphate in its trivalent form, but this step is inhibited by pyrophosphate, itself a source of phosphate when hydrolysed by alkaline phosphatase. Separately, matrix vesicles create nucleation sites and may indirectly disrupt vascular smooth muscle cells. Metabolic acidosis acts at every point to delay mineralization. The diuretic acetazolamide creates a sustained mild acidosis with some phosphate loss and, though usually ineffective in the experimental model, has been used with success in certain clinical conditions. We suggest that acetazolamide, well studied and tolerated, might inhibit progression of vascular calcification in subjects at risk through its dual action of lowering tissue pH and local phosphate concentration.

Comparison of atherosclerotic inflammation and calcification in subjects with end stage renal disease (ESRD) on hemodialysis to normal controls utilizing 18F-FDG PET/CT.

Subjects with end stage renal disease (ESRD) are exposed to increased morbidity and mortality due to cardiovascular events. The primary underlying mechanism has been suggested as accelerated atherosclerosis in these patients. Our aim was to compare the atherosclerotic inflammation and calcification in subjects with ESRD on hemodialysis to that in normal controls utilizing fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT). Forthy two subjects who underwent 18F-FDG PET/CT imaging were retrospectively studied. Twenty one were subjects with ESRD on hemodialysis (67±11 years old; 14 male, 7 female) and 21 were age- and gender-matched controls. Average standardized uptake value maximum (SUVmax) and SUVmean for 4 segments of the aorta (ascending, arch, descending, abdominal) and for the common iliac arteries and common femoral arteries were measured. Standardized uptake value maximum and SUVmean for right atrial blood pool were also measured as the background. Average SUVmax, average SUVmean, average SUVmax/background ratio, and average SUVmean/background ratio were compared between subject groups for all segments. Presence or absence of macroscopic calcification on CT images for each arterial segment based on visual qualitative assessment was also noted and compared. For statistical analysis, two-sided t-test was used for continuous variables, and chi-square test was used for categorical variables. We considered a P value of <0.05 as statistically significant. Average SUVmax and SUVmean were statistically significantly greater in subjects with ESRD than in controls in all arterial segments. Average SUVmax/background ratios were statistically significantly greater in subjects with ESRD compared to normal controls in all arterial segments except for the left femoral artery. Average SUVmean/background ratios were statistically significantly greater in subjects with ESRD compared to normal controls in all arterial segments except for the right and left femoral arteries. Presence of calcification on CT was more frequently encountered in all arterial segments in subjects with ESRD, and was statistically significantly greater for the aortic arch, descending aorta, and right and left femoral arteries. SUV measurements representing the atherosclerotic inflammatory changes and macroscopic atherosclerotic calcifications appear to be accelerated in subjects with ESRD on hemodialysis compared to normal controls. Fluorine-18 FDG PET/CT is a valuable diagnostic tool for verifying and quantifying accelerated atherosclerosis secondary to ESRD.

Matrix metalloproteinase-10 deficiency delays atherosclerosis progression and plaque calcification

Background and aimsMatrix metalloproteinases (MMPs) have been implicated in atherosclerosis and vascular calcification. Among them, we reported that MMP10 is present in human atheroma, associated with atherosclerosis. However, it remains unclear whether MMP10 is involved in atherogenesis and vascular calcification. MethodsMMP10 was measured in serum from patients with subclinical atherosclerosis and analyzed in carotid endarterectomies by immunostaining. ApoE-deficient mice (Apoe−/−) were crossed to MMP10-deficient (Mmp10−/−) mice and followed up to 20 months. Plaque area and composition were assessed by histology and immunohistochemistry. Inflammatory markers were measured in atherosclerotic plaques by RT-qPCR, and leukocyte subpopulations were analyzed by flow cytometry. In vitro calcification assays were performed in aortic vascular smooth muscle cells (VSMC). ResultsMMP10 serum levels were associated with coronary calcification in subjects with subclinical atherosclerosis. Immunostaining revealed MMP10 expression in human atheromas, spatially associated with calcification areas, and complicated plaques released higher amounts of MMP10 than non-diseased segments. Interestingly, vascular MMP10 expression was confined to the atherosclerotic lesion in Apoe−/− mice, and Apoe−/−Mmp10−/− showed a substantial reduction in atherosclerotic lesion size, macrophage content and plaque calcification. Reduced local and systemic inflammatory markers could be demonstrated in Apoe−/−Mmp10−/− by gene expression and flow cytometry analysis. Calcium phosphate deposition and vascular calcification markers were downregulated in VSMC from Apoe−/−Mmp10−/− mice. ConclusionsDelayed plaque progression and altered cellular composition in the absence of MMP10 suggests that MMP10 plays a role in atherosclerosis, favoring inflammation, development and complication of the plaque.

Elevated serum uric acid predicts the development of moderate coronary artery calcification independent of conventional cardiovascular risk factors

Background and aimsHyperuricemia was frequently noted in subjects with a high risk of cardiovascular disease (CVD). This study aimed to elucidate whether serum uric acid (SUA) is associated with development of moderate coronary artery calcification in generally healthy adults. MethodsA total of 9297 subjects underwent multidetector CT for the evaluation of CAC at least two times during their annual health examinations. Among them, 4461 participants without CVD history and who had no (scores 0) or minimal CAC (scores 1–10) in their first examination were enrolled. The association between SUA as a continuous and categorical variable and development of moderate coronary artery calcification (CAC score > 100) was assessed by Cox regression analysis. Receiver-operating characteristic (ROC) curves were constructed to investigate the diagnostic efficacy of SUA. ResultsDuring a median follow-up of 4.1 years, 131 incident cases of moderate calcification developed. Baseline SUA concentration was significantly higher in subjects with progression to moderate coronary artery calcification (6.6 ± 1.3 vs. 5.8 ± 1.3 mg/dL, p < 0.001). SUA as a continuous variable (per 1 mg/dL) and divided into quartiles was positively associated with a higher risk of development of moderate calcification after adjustment for conventional CVD risk factors. The addition of SUA to the conventional CVD risk factors improved the predictive power for development of moderate coronary artery calcification. ConclusionsSUA was an independent predictor for development of moderate coronary artery calcification in subjects with no or minimal calcification.

Prognostic significance of arterial stiffness and osteoprotegerin in patients with stable coronary artery disease.

Arterial stiffness and vascular calcification significantly contribute to coronary atherosclerosis progression. The prognostic value of increased arterial stiffness and vascular calcification in subjects with stable coronary artery disease (CAD) after percutaneous coronary intervention(PCI) is currently under question. We randomly enrolled 262 patients with stable CAD 1month after successful PCI. Carotid-femoral pulse wave velocity (PWV) was measured as a well-established index of central aortic stiffness. Osteoprotegerin (OPG) plasma levels were measured as a biomarker of vascular calcification. Patients were followed up prospectively up to 52months. The primary endpoint was the composite of death from cardiovascular causes, myocardial infarction, stroke or hospitalization for cardiovascular causes. During the follow-up period, 48 patients presented the primary composite endpoint. Subjects who presented the primary endpoint, compared to subjects free of cardiovascular events, had significantly increased PWV (9.45±2.19m/s vs 8.73±2.07m/s, P=.04) and OPG levels (4.21±2.19pmol/L vs 3.18±1.74pmol/L, P=.003). Survival analysis indicated that PWV predicted adverse cardiac events MACE (Hazard ratio=1.29 95%CI: 1.07-1.57, P=.008) independently from confounders such as age, sex, smoking habits, ejection fraction, extent of coronary artery disease, hypertension and diabetes mellitus. Interestingly, for every increase in pulse wave velocity by 1m/s, there is an anticipated increase in the risk of major adverse cardiovascular event (MACE) by 29%. These findings extend the current knowledge concerning the role of arterial stiffness as powerful biomarkers in cardiovascular disease. Measurement of PWV might have a role in ascertaining prognosis and managing treatment in patients with stable CAD after PCI.

Increased risk for development of coronary artery calcification in subjects with non-alcoholic fatty liver disease and systemic inflammation.

BackgroundRecent studies have suggested the importance of non-alcoholic fatty liver disease (NAFLD) and systemic inflammation in the development of atherosclerosis. The aim of this study was to compare the risk for coronary artery calcification (CAC) development according to the status of NAFLD and inflammation over four years of follow-up in subjects without baseline CAC.MethodsA total of 1,575 participants in a health screening program were divided into four groups according to baseline NAFLD state and high-sensitivity C-reactive protein (hs-CRP) (median 0.06 mg/L) levels as follows: no NAFLD and hs-CRP <0.06 mg/L, no NAFLD and hs-CRP ≥0.06 mg/L, NAFLD and hs-CRP <0.06 mg/L, and NAFLD and hs-CRP ≥0.06 mg/L. Coronary artery calcium score (CACS) was repeatedly measured by multi-detector computed tomography at four-year intervals and CAC development during those intervals was monitored in subjects with baseline CACS = 0.ResultsOver four years, 148 subjects (9.4%) developed CAC. The proportion of subjects who developed CAC was significantly higher in subjects with NAFLD at baseline compared with those without NAFLD at baseline (6.8 vs. 12.4%, p<0.01), and it was also higher in subjects with hs-CRP ≥0.06 mg/L compared with those with hs-CRP <0.06 mg/L (7.2 vs. 11.5%, p<0.01). In addition, the proportion of subjects who developed CAC was highest in subjects with NAFLD and hs-CRP ≥0.06 mg/dL, followed by subjects with NAFLD, subjects without NAFLD and hs-CRP ≥0.06 mg/L, and subjects without NALFD and hs-CRP <0.05 mg/L at baseline, in that order (13.7, 10.0, 8.3, and 5.8%, respectively; p for trend<0.01). The odds ratio for CAC development was highest in subjects with NAFLD and hs-CRP ≥0.06 mg/L (1.67, 95% CI 1.01–2.77), though it was attenuated after adjustment for body mass index.ConclusionsThe concomitant presence of NAFLD and systemic inflammation as assessed by hs-CRP increases the risk of CAC development over four years.

Association of plasma fetuin-a levels with peripheral arterial disease and lower extremity arterial calcification in subjects with type 2 diabetes mellitus

AimsFetuin-A is a hepatic glycoprotein that is involved in insulin resistance and atherosclerosis. Herein we examined the association of plasma fetuin-A levels with peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM). Material and MethodsA total of 71 patients with T2DM and 57 non-diabetic individuals were recruited. Diagnosis of PAD was based on the absence of triphasic waveform at pedal arteries, while ankle–brachial index (ABI) was calculated. Radiographs of both feet and ankles were taken for the assessment of lower extremity arterial calcification (LEAC). Plasma fetuin-A levels were measured using ELISA. ResultsPatients with T2DM had higher fetuin-A levels than non-diabetic participants. Participants with diabetes and PAD had lower fetuin-A levels than non-PAD diabetic patients. In subjects with T2DM fetuin-A levels were associated with ABI. Multivariate analysis demonstrated that in patients with T2DM the odds of PAD increased with long diabetes duration, smoking, presence of arterial hypertension and dyslipidemia, as well as with lower fetuin-A levels. A trend towards higher fetuin-A levels in subjects with less severe LEAC was found. ConclusionPlasma fetuin-A levels are lower in patients with T2DM and PAD and are associated with PAD, irrespective of traditional cardiovascular risk factors. Moreover, fetuin-A may be involved in arterial calcification.

Fasting plasma glucose levels and coronary artery calcification in subjects with impaired fasting glucose.

BACKGROUNDPrediabetes is associated with an increased risk of cardiovascular disease (CVD). While the association of impaired glucose tolerance with CVD has been shown in many studies, the relationship between impaired fasting glucose (IFG) and CVD remains unclear.OBJECTIVESThe purpose of this study was to compare the coronary artery calcium (CAC) scores of participants with normal fasting glucose versus those with IFG, according to fasting plasma glucose (FPG) levels, and to assess whether differences in CAC scores were independent of important confounders.DESIGNRetrospective study.SETTINGHealth Promotion Center of the University Hospital (Gyeonggi-do, South Korea), during the period 2010–2014.PATIENTS AND METHODSParticipants were enrolled from the general population who visited for a medical check-up. CAC was assessed in asymptomatic individuals by multidetector computed tomography. Anthropometric parameters and metabolic profiles were also recorded. Subjects were divided into four fasting glucose groups. Participants with a history of CVD or diabetes mellitus were excluded.MAIN OUTCOME MEASURESCorrelation between FPG and CAC scores, CAC score categories, and association between CAC score and FPG categories.RESULTSOf 1112 participants, 346 (34.2%) had a CAC score >0. FPG values in the IFG patients were positively but weakly correlated with CAC scores (r=0.099, P=.001). The incidence of CAC differed according to FPG level (P<.001) and in Kruskal-Wallis test the mean CAC score differed by FPG group (P<.001). After adjustment for other factors in a multiple logistic regression analysis, those subjects with FPG ≥110 mg/dL had a significantly higher risk of CAC than did subjects with normal fasting glucose (110≤FPG [mg/dL] <120, OR=2.507, P=.002; 120≤FPG [mg/dL] <126, OR=3.568, P=.001 vs. <100 mg/dL)CONCLUSIONIFG (especially FPG≥110 mg/dL) could be an independent risk factor for CAC. These associations were not altered after adjustment for other possible confounders.LIMITATIONSPossible misclassification because data taken from a single blood test. No HbA1c tests or repeated FPG tests. No adjustment for other potentially important confounders.

Biomarkers Associated with Vascular Calcification in Peritoneal Dialysis.

♦ Vascular calcification is strongly associated with cardiovascular disease and mortality. However, some factors related to vascular calcification in patients with end-stage renal disease receiving peritoneal dialysis (PD) remain unknown. This study aimed to evaluate the associations of osteoprotegerin (OPG), osteopontin (OPN), osteocalcin (OCN), fibroblast growth factor 23 (FGF-23), magnesium, and phosphate clearance with vascular calcification in PD subjects, assessed by plain radiographs. ♦ Simple vascular calcification scores (SVCS) obtained from plain X-rays of the pelvis and hands, and the Kauppila Index (KI) from lateral lumbar X-rays were assessed in 76 adults receiving PD for ≥ 6 months (43 women, median age 39 years, median time on PD 1.4 years). Levels of OPG, OPN, OCN, and FGF-23 were determined by luminometry. ♦ Serum OPG levels were higher in subjects with vascular calcification (n = 22 with SVCS > 3; n = 19 with KI > 7) compared with those with less calcification (p < 0.001). Spearman's correlation coefficients between OPG and SVCS and KI were r = 0.49 and r = 0.51, respectively (both p < 0.001). Subjects with vascular calcification had significantly lower renal phosphate clearance. Multiple regression analysis showed that vascular calcification assessed by SVCS was associated with age (r = 0.2, p = 0.042), diabetes mellitus (r = 2.4, p < 0.001), body mass index (BMI) (r = 0.09, p = 0.037), and OPG (r = 0.22, p = 0.001). Vascular calcification assessed by KI was associated with age (r = 0.16, p < 0.001), time on PD (r = 0.54, p = 0.001) and OPG (r = 0.08, p = 0.04). Osteocalcin, OPN, FGF-23, and magnesium were not associated with vascular calcification. ♦ Higher levels of OPG were consistently associated with vascular calcification in subjects on PD.

Increased risk for development of coronary artery calcification in insulin-resistant subjects who developed diabetes: 4-year longitudinal study

ObjectiveCoronary artery calcification (CAC) is considered a surrogate marker for atherosclerotic burden. The aim of this study was to analyze the risk of incident CAC associated with diabetes development in non-diabetic subjects with zero CAC score (CACS) at baseline. Methods2076 non-diabetic participants (mean age 40 years) in a health screening program in whom CACS were repeatedly measured by multi-detector computed tomography in four years of intervals and with zero CACS at baseline, were retrospectively analyzed. Glycemic status was assessed in both years, with subjects divided into three groups: subjects with ‘no progression’, ‘normal to impaired fasting glucose (IFG)’ and ‘progression to diabetes’. Insulin resistance was assessed by homeostasis model assessment-insulin resistance (HOMA-IR) index. ResultsOver 4 years, 204 subjects (9.8%) developed CAC. Subjects who developed diabetes showed the highest proportion of subjects with incident CAC among the three groups (21.0% vs. 9.3 and 10.4% in non-progressors and subjects from normal to IFG). The subjects with HOMA-IR level in higher half at baseline showed significantly increased risk for incident CAC in subjects who progressed from normal to IFG and in subjects who developed diabetes (1.740; 95% CI 1.014–2.985, 2.449; 95% CI 1.159–5.174) even after adjustment for confounding variables, whereas subjects with HOMA-IR level in lower half at baseline showed no significantly increased risk for incident CAC even in subjects who developed diabetes. ConclusionsIn this non-diabetic population, we found that increased risk for incident CAC in relation to diabetes development over 4 years was pronounced only in subjects with insulin resistance at baseline.

Vascular Calcification in Type 2 Diabetes: A Role for Allopurinol?

Vascular calcification contributes significantly to the vascular damage burden in type 2 diabetes. Chronic hyperglycaemia is the driver of initiation and progression of vascular damage in these subjects. Enhanced oxidative stress is widespread in these subjects due to complex metabolic, cytokine, inflammatory and ageing factors, on the background of chronic hyperglycaemia. All these factors together contribute to an increased risk of vascular damage leading to atherosclerosis and vascular calcification. The xanthine oxidase system is a major contributor to the development of enhanced oxidative stress through generation of excessive free radicals. Current standard therapy is focused on controlling hyperglycaemia and screening/treatment of known co-morbidities. However, these therapies do not target oxidative stress. Allopurinol, a potent xanthine oxidase inhibitor has demonstrated beneficial effects on several parameters of vascular health such as reduction in oxidative stress, proteinuria, reversal of vascular damage, regression of ventricular hypertrophy and arresting the rate of progression of chronic kidney disease. A randomised clinical trial of Allopurinol for amelioration of oxidative stress, endothelial cell dysfunction and vascular calcification in subjects with type 2 DM may be helpful to explore its potential in this area.

Calcium–phosphorus product concentration is a risk factor of coronary artery disease in metabolic syndrome

BackgroundHigh serum phosphorus and the calcium–phosphorus product concentration has been associated with increased mortality and cardiovascular events in patients with chronic kidney disease. ObjectiveThis study was designed to determine the relationship between calcium–phosphorus product concentration and the presence of coronary artery calcification in subjects with metabolic syndrome (MetS). MethodsWe reviewed the medical records of 2056 general subjects with a mean age of 55.1 ± 9.9 years and a glomerular filtration rate of 88.9 ± 16.2 mL/min/1.73 m2. The enrolled subjects consisted of 384 (18.7%) subjects with MetS and 1672 (81.3%) subjects without MetS. The severity of coronary artery calcification was assessed by the coronary artery calcification score (CACS) using multi-detector computed tomography (MDCT). ResultsThe CACS correlated with calcium–phosphorus product concentration in subjects with MetS (r = 0.184, P < 0.01). The odds ratio of calcium–phosphorus product concentration having CACS >50 was 1.053 in subjects with MetS (P < 0.05). After adjustment for age, sex, diabetes, and dyslipidemia, calcium–phosphorus product concentrations had a positive correlation with CACS in subjects with MetS. In single regression analysis, calcium–phosphorus product concentration as independent variable was the significant predictor of CACS in subjects with MetS. Using a multivariate analysis, calcium–phosphorus product concentration remained a significant factor associated with CACS in subjects with MetS. ConclusionsCalcium–phosphorus product concentration was weakly associated with CACS and an independent factor predicting for CACS by MDCT in subjects with MetS. These results suggest that calcium–phosphorus product concentration might be considered as a risk factor of coronary artery disease in subjects with MetS.

Styloid process elongation and calcification in subjects with tmd: clinical and radiographic aspects

Knowledge of the Eagle's syndrome shows that its symptoms can be very easily confused with other types of craniomandibular disorders, especially temporomandibular disorders (TMD). The aim of this study was to find a possible correlation between the presence of TMD and elongation of the styloid process as well relate to presence of calcification of the stilohyoid chain. Fifty patients with TMD, confirmed from the RDC/TMD, were examined clinically and radiographically. Radiographic documentation consisted of digital panoramic radiograph and digital lateral cephalometric radiograph. Radiocef software (Radiomemory) was used for the analysis of radiographs by means of specific cephalometric tracing and linear measurements of the styloid process. Each radiograph was traced and measured three times with intervals of 1 month to spread the error. Statistical analysis was performed by Pearson's test (p=0.001) using Biostat 4.0 statistical software. Result showed an incidence of 76% elongation of the styloid process in the sample. There was a correlation between the bilateral measures taken in panoramic radiographs (?<0.001) and also for measures of styloid process length carried out in different panoramic radiographs and lateral cephalometric radiographs (?<0.001). It was concluded that there is prevalence of elongated styloid process in patients with TMD. However, no relationship was found between measurements on the stylohyoid chain and symptoms of headache, orofacial pain, tinnitus and vertigo.

Vitamin D Deficiency and Coronary Artery Calcification in Subjects With Type 1 Diabetes

OBJECTIVEThe objective of this study is to examine the relationship among serum levels of 25-hydroxyvitamin D (25[OH]D), polymorphisms in vitamin D-associated genes, and the presence and progression of coronary artery calcification (CAC) in adults with type 1 diabetes.RESEARCH DESIGN AND METHODSThis prospective study included 374 non-Hispanic white individuals with type 1 diabetes (mean age 40 ± 9 years; 46% were male). CAC was measured at the baseline and 3- and 6-year follow-up visits were determined by electron beam computed tomography. Serum 25[OH]D levels were measured by liquid chromatography tandem mass spectrometry at the 3-year visit.RESULTSNormal (>30 ng/mL), insufficient (20–30 ng/mL), and deficient (<20 ng/mL) 25-[OH]D levels were present in 65%, 25%, and 10% of the individuals with type 1 diabetes, respectively. 25[OH]D deficiency was associated with the presence of CAC at the 3-year visit, odds ratio (OR) = 3.3 (95% CI 1.6–7.0), adjusting for age, sex, and hours of daylight. In subjects free of CAC at the 3-year visit, 25[OH]D deficiency predicted the development of CAC over the next 3 years in those with the vitamin D receptor M1T CC genotype (OR = 6.5 [1.1–40.2], P = 0.04) than in those with the CT or TT genotype (OR = 1.6 [0.3–8.6], P = 0.57).CONCLUSIONSVitamin D deficiency independently predicts prevalence and development of CAC, a marker of coronary artery plaque burden, in individuals with type 1 diabetes.

Insulin Resistance, Defective Insulin-Mediated Fatty Acid Suppression, and Coronary Artery Calcification in Subjects With and Without Type 1 Diabetes

OBJECTIVETo assess insulin action on peripheral glucose utilization and nonesterified fatty acid (NEFA) suppression as a predictor of coronary artery calcification (CAC) in patients with type 1 diabetes and nondiabetic controls.RESEARCH DESIGN AND METHODSInsulin action was measured by a three-stage hyperinsulinemic-euglycemic clamp (4, 8, and 40 mU/m2/min) in 87 subjects from the Coronary Artery Calcification in Type 1 Diabetes cohort (40 diabetic, 47 nondiabetic; mean age 45 ± 8 years; 55% female).RESULTSPeripheral glucose utilization was lower in subjects with type 1 diabetes compared with nondiabetic controls: glucose infusion rate (mg/kg FFM/min) = 6.19 ± 0.72 vs. 12.71 ± 0.66, mean ± SE, P < 0.0001, after adjustment for age, sex, BMI, fasting glucose, and final clamp glucose and insulin. Insulin-induced NEFA suppression was also lower in type 1 diabetic compared with nondiabetic subjects: NEFA levels (μM) during 8 mU/m2/min insulin infusion = 370 ± 27 vs. 185 ± 25, P < 0.0001, after adjustment for age, sex, BMI, fasting glucose, and time point insulin. Lower glucose utilization and higher NEFA levels, correlated with CAC volume (r = −0.42, P < 0.0001 and r = 0.41, P < 0.0001, respectively) and predicted the presence of CAC (odds ratio [OR] = 0.45, 95% CI = 0.22–0.93, P = 0.03; OR = 2.4, 95% CI = 1.08–5.32, P = 0.032, respectively). Insulin resistance did not correlate with GHb or continuous glucose monitoring parameters.CONCLUSIONSType 1 diabetic patients are insulin resistant compared with nondiabetic subjects, and the degree of resistance is not related to current glycemic control. Insulin resistance predicts the extent of coronary artery calcification and may contribute to the increased risk of cardiovascular disease in patients with type 1 diabetes as well as subjects without diabetes.

Study design and subject baseline characteristics in the ADVANCE Study: effects of cinacalcet on vascular calcification in haemodialysis patients

The ADVANCE (A Randomized Study to Evaluate the Effects of Cinacalcet plus Low-Dose Vitamin D on Vascular Calcification in Subjects with Chronic Kidney Disease Receiving Haemodialysis) Study objective is to assess the effect of cinacalcet plus low-dose active vitamin D versus flexible dosing of active vitamin D on progression of coronary artery calcification (CAC) in haemodialysis patients. We report the ADVANCE Study design and baseline subject characteristics. ADVANCE is a multinational, multicentre, randomized, open-label study. Adult haemodialysis patients with moderate to severe secondary hyperparathyroidism (intact parathyroid hormone [iPTH] >300 pg/mL or bio-intact PTH >160 pg/mL) and baseline CAC score >or=30 were stratified by CAC score (>or=30-399, >or=400-999, >or=1000) and randomized in a 1:1 ratio to cinacalcet (30-180 mg/day) plus low-dose active vitamin D (cinacalcet group) or flexible dosing of active vitamin D alone (control). The study had three phases: screening, 20-week dose titration and 32-week follow-up. CAC scores obtained by cardiac computed tomography were determined at screening and weeks 28 and 52. The primary end point was percentage change in CAC score from baseline to Week 52. Subjects (n = 360) were randomized to cinacalcet or control. Mean age was 61.5 years, 43% were women, and median dialysis vintage was 36.7 months (range, 2.7-351.5 months). The baseline geometric mean CAC score by the Agatston method was 548.7 (95% confidence interval, 480.5-626.6). Baseline CAC score was independently associated with age, sex, dialysis vintage, diabetes and iPTH. Subjects also had extensive aortic and valvular calcification at baseline. Subjects enrolled in ADVANCE have extensive CAC at baseline. The ADVANCE Study should help determine whether cinacalcet attenuates progression of vascular calcification.