Association of 25(OH)D and PTH with Metabolic Syndrome and Its Traditional and Nontraditional Components

Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 10/2010; 96(1):168-75. DOI: 10.1210/jc.2010-1439
Source: PubMed


Emerging evidence suggests that 25-hydroxy vitamin D [25(OH)D] and PTH may play a role in the etiology of the metabolic syndrome (MetS). However, evidence to date is limited and inconsistent, and few studies have examined associations with nontraditional MetS components.
The objective of the study was to examine the association of vitamin D and PTH with MetS and its traditional and nontraditional components in a large multiethnic sample.
In this cross-sectional study, we examined 654 participants from London and Toronto, Ontario, Canada, aged 30 yr and older with risk factors for type 2 diabetes.
Presence of MetS and its traditional and nontraditional components was measured.
Approximately 43% of the study participants were classified as having MetS. Higher 25(OH)D was significantly associated with a reduced presence of MetS after adjustment for age, sex, season, ethnicity, supplement use, physical activity, and PTH (odds ratio 0.76, 95% confidence interval 0.62-0.93). PTH was not associated with the presence of MetS after multivariate adjustment. Multivariate linear regression analyses indicated significant adjusted inverse associations of 25(OH)D with waist circumference, triglyceride level, fasting insulin, and alanine transaminase (P < 0.041). Elevated PTH was positively associated with waist circumference and high-density lipoprotein cholesterol (P < 0.04). Other associations between PTH and MetS components were attenuated after adjustment for adiposity.
Serum 25(OH)D, but not PTH, was significantly associated with MetS as well as a number of MetS components after multivariate adjustment. These results suggest that low 25(OH)D may play a role in the etiology of the MetS.

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    • "However, even across the normal range, higher PTH is accompanied by a substantially increased risk of cardiovascular events and mortality[5]–[7]. Some studies have reported associations between PTH and metabolic syndrome components[47], but in the NHANES 2001–2006 cohort, diastolic blood pressure is the only cardiovascular risk factor independently associated with greater PTH[48]. As with the reported association between PTH and cardiovascular mortality, we find that higher-normal PTH is associated with greater albuminuria independently of all traditional risk factors and previous history of cardiovascular disease. "
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    ABSTRACT: Even within accepted normal ranges, higher serum phosphorus, dietary phosphorus density, parathyroid hormone (PTH) and alkaline phosphatase (ALP) are independent predictors of cardiovascular mortality. Lower serum 25-hydroxy vitamin D (25(OH)D) also predicts adverse cardiovascular outcomes. We hypothesized that vascular dysfunction accompanying subtle disturbances of these bone metabolism parameters would result in associations with increased low grade albuminuria. We examined participants in the National Health and Nutrition Examination Surveys 1999-2010 (N = 19,383) with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m(2) and without severe albuminuria (urine albumin:creatinine ratio (ACR) <300 mg/g). Albuminuria was quantified as ACR and fractional albumin excretion (FEalb). Increasing quintiles of dietary phosphorus density, serum phosphorus and ALP were not associated with higher ACR or FEalb. The lowest versus highest quintile of 25(OH)D was associated with greater albuminuria, but not after adjustment for other covariates including cardiovascular risk factors. An association between the highest versus lowest quintile of bone-specific ALP and greater ACR persisted after covariate adjustment, but was not accompanied by an independent association with FEalb. Increasing quintiles of PTH demonstrated associations with both higher ACR and FEalb that were not abolished by adjusting for covariates including age, gender, race, body mass index, diabetes, blood pressure, history of cardiovascular disease, smoking, eGFR, 25(OH)D, season of measurement, lipids, hemoglobin and C-reactive protein. Adjusted increases in ACR and FEalb associated with the highest versus lowest quintile of PTH were 19% (95% confidence interval 7-28% p<0.001) and 17% (8-31% p = 0.001) respectively. In this population, of the bone mineral parameters associated with cardiovascular outcomes, only PTH is independently associated with ACR and FEalb.
    PLoS ONE 02/2014; 9(2):e88388. DOI:10.1371/journal.pone.0088388 · 3.23 Impact Factor
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    • "Vitamin D deficiency has been implicated in susceptibility to the development of hypertension, obesity, insulin resistance , T2DM and MetS [102] [103]. Accordingly, subjects with vitamin D insufficiency (defined as 25-OH vitamin D levels <20 ng/ml) show a higher risk for insulin resistance and MetS [104] [105]. Moreover, plasma 25-OH vitamin D levels are positively associated with insulin sensitivity and negatively associated with first-and second-phase insulin secretion, triglyceride levels, fasting insulin and waist circumference [106]. "
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    ABSTRACT: The metabolic syndrome (MetS) is a clustering of risk factors for the development of cardiovascular disease and type 2 diabetes mellitus. These risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. MetS has become a serious public health and clinical problem whose prevalence and incidence are increasing along with the worldwide rise in rates of obesity and sedentary lifestyles. A number of studies have shown that MetS is associated with a state of low-grade inflammation, characterized by abnormal pro-inflammatory cytokine production, increased acute-phase reactants, and activation of a network of inflammatory signalling pathways. Moreover, MetS has also been linked to oxidative stress, a consequence of a reduction in the antioxidant systems and an increase in the production of reactive oxygen species. Nevertheless, agreement exists that dietary intervention may modulate the pro-inflammatory state and lessen oxidative stress related to MetS, thereby decreasing the cardiovascular risk. In this review we address the current available evidence regarding dietary modulation of inflammation and oxidative stress associated with MetS.
    Current Vascular Pharmacology 10/2013; 11(6). DOI:10.2174/15701611113116660175 · 2.97 Impact Factor
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    • "The association of PTH with lipid concentrations, specifically the cholesterol levels was demonstrated earlier and we suggest that this is mainly due to the positive association of PTH to body composition and adiposity, rather than the cholesterol itself [19,20]. Also, the inverse association of FT3 to circulating levels of 25(OH)D should be interpreted with caution. "
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    ABSTRACT: Sub-clinical hypothyroid dysfunction, a relatively understudied disorder in the Kingdom of Saudi Arabia (KSA), has significant clinical implications if not properly monitored. Also from KSA, more than 50% of the population suffer from hypovitaminosis D (<50nmol/l). In this cross-sectional case-control study, we described the differences and associations in the metabolic patterns of adult Saudis with and without hypothyroid dysfunction in relation to their vitamin D status, PTH, calcium and lipid profile. A total of 94 consenting adult Saudis [52 controls (without subclinical hypothyroidism), 42 cases (previously diagnosed subjects)] were included in this cross-sectional study. Anthropometrics were obtained and fasting blood samples were taken for ascertaining lipid and thyroid profile, as well as measuring PTH, 25(OH) vitamin D and calcium. Cases had a significantly higher body mass index than the controls (p < 0.001). Circulating triglycerides was also significantly higher in cases than the controls (p = 0.001). A significant positive association between HDL-cholesterol and PTH (R = 0.56; p = 0.001), as well as a negative and modestly significant negative association between LDL-cholesterol and PTH (R = - 20.0; p = 0.04) were observed. FT3 was inversely associated with circulating 25 (OH) vitamin D (R = -0.25; p = 0.01). Patients with hypothyroid dysfunction possess several cardiometabolic risk factors that include obesity and dyslipidemia. The association between PTH and cholesterol levels as well as the inverse association between vitamin D status and FT3 needs to be reassessed prospectively on a larger scale to confirm these findings.
    BMC Endocrine Disorders 08/2013; 13(1):31. DOI:10.1186/1472-6823-13-31 · 1.71 Impact Factor
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