Vitamin D, parathyroid hormone, glucose metabolism and incident diabetes in the multiethnic study of atherosclerosis

Abstract

IntroductionHigher concentrations of serum 25-hydroxyvitamin D (25(OH)D) and lower concentrations of parathyroid hormone (PTH) are associated with lower insulin resistance and incident diabetes in non-Hispanic White and Hispanic Americans. Results are mixed in other populations, with no observational studies in a large multiethnic cohort. The association of serum 25(OH)D with diabetes may vary by adiposity level.Research design and methodsAmong 5611 participants in the Multi-Ethnic Study of Atherosclerosis without diabetes at baseline, cross-sectional associations of serum 25(OH)D with homeostasis model assessment of insulin resistance (HOMA-IR) and HOMA-β were examined using linear regressions. The association of 25(OH)D with incident diabetes over 9 years was examined using Cox proportional hazard regression.ResultsBlack Americans had the highest proportion of individuals with 25(OH)D<20 ng/mL (61%) and White Americans had the least (17%). Serum 25(OH)D was inversely associated with HOMA-IR in fully adjusted models (−0.34% difference in HOMA-IR per ng/mL higher 25(OH)D, p<0.0001). Longitudinally, a 1 ng/mL higher serum 25(OH)D was associated with 2% lower risk of incident diabetes (HR 0.982, CI 0.974 to 0.991), and a 1 pg/mL higher serum PTH was associated with 1% higher risk of incident diabetes (HR 1.007, CI 1.004 to 1.010), both prior to adjustment for waist circumference. After adjusting for waist circumference, a 1 ng/mL higher 25(OH)D was associated with 1% lower risk of incident diabetes (HR 0.991, CI 0.983 to 1.000). The magnitude of association of serum 25(OH)D with incident diabetes was largest at lower waist circumference (p for interaction=0.025). There was no heterogeneity by race/ethnicity (p=0.317).ConclusionsSerum 25(OH)D is inversely associated with insulin resistance and incident diabetes in a diverse cohort, including non-Hispanic White, Black, Hispanic and Chinese Americans. Future research should explore mechanisms for the interaction between serum 25(OH)D and adiposity in this relationship.

The Role of Vitamin D in Reducing the Risk of Metabolic Disturbances That Cause Cardiovascular Diseases

“…It is also thought that PTH might block the interchange of sodium and hydrogen, which adds to the impact of spontaneous hypertension [41]. In addition, the increase in PTH hormone produces an increase in insulin resistance and inflammation, both of which contribute to the development of atherosclerosis [42]. With regard to the proliferation and differentiation of cells, vitamin D affects the activity of several genes that are essential for the activation of numerous signaling pathways, as well as the equilibrium of the extracellular matrix, hence preserving the development and remodeling of blood vessels [43].…”

The Relationship between Renin–Angiotensin–Aldosterone System (RAAS) Activity, Osteoporosis and Estrogen Deficiency in Type 2 Diabetes

“…MR and AT1R are expressed in the parathyroid glands [56]. T2D leads to upregulation of aldosterone and the ACE/Ang II/AT1R axis, potentially resulting in the parathyroid glands being over-stimulated and leading to increased PTH and 1,25-hydroxy vitamin D concentrations that could further lead to osteoporosis [3,50,59,60]. Furthermore, PTH stimulates the release of aldosterone from the adrenal glands due to the expression of type 1 PTH receptors in the adrenal glands, indicating a cycle of continued activity [56].…”