title: Prospective associations of vitamin D status with β-cell function, insulin sensitivity, and glycemia: the impact of parathyroid hormone status.
abstract: Previous studies have yielded conflicting findings on the relationship between low vitamin D (25-OH-D) and impaired glucose homeostasis. In this context, we hypothesized that combined assessment of 25-OH-D with its regulator parathyroid hormone (PTH) may be required for optimal evaluation of the impact of vitamin D status on glucose metabolism. Thus, we evaluated the prospective associations of 25-OH-D and PTH at 3 months postpartum with β-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]), insulin sensitivity (Matsuda index), and glycemia at 12 months postpartum in 494 women undergoing serial metabolic characterization. Notably, 32% of those with prediabetes/diabetes mellitus at 12 months postpartum had both vitamin D deficiency and PTH in the highest tertile at 3 months postpartum. On multiple-adjusted linear regression analyses, vitamin D deficiency/insufficiency with PTH in the highest tertile at 3 months independently predicted poorer β-cell function (P = 0.03) and insulin sensitivity (P = 0.01) and increased fasting (P = 0.03) and 2-h glucose (P = 0.002) at 12 months postpartum. In contrast, vitamin D deficiency/insufficiency with lower PTH did not predict these outcomes. In conclusion, only vitamin D deficiency/insufficiency with increased PTH is an independent predictor of β-cell dysfunction, insulin resistance, and glycemia, highlighting the need for consideration of the PTH/25-OH-D axis when studying the impact of vitamin D status on glucose homeostasis.
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Caroline K
authors.initials: CK
authors.lastname: Kramer
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Balakumar
authors.initials: B
authors.lastname: Swaminathan
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hanley
authors.affiliation: Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Connelly
authors.affiliation: Division of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mathew
authors.initials: M
authors.lastname: Sermer
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada rretnakaran@mtsinai.on.ca.
authors.forename: Ravi
authors.initials: R
authors.lastname: Retnakaran
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000097:blood* / Q000378:metabolism; D049590:Postpartum Period / Q000378:metabolism; D011446:Prospective Studies; D014807:Vitamin D / Q000097:blood* / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000150:complications
chemical_list: D001786:Blood Glucose; D010281:Parathyroid Hormone; D014807:Vitamin D