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Threshold Effects of 25-Hydroxyvitamin D on Glucose Tolerance and Insulin Resistance

A threshold level of 25-hydroxyvitamin D may exist with potential benefits on glycemic control…. 

Vitamin D supplementation is a common practice throughout the United States. Levels of 25-hydroxyvitamin D, 25(OH)D, that are considered normal are based upon guidelines established primarily from bone metabolism studies. Aside from the important role of Vitamin D on bone metabolism, several associations between non-bone endpoints have been found, including; glucose intolerance, type 2 diabetes, insulin resistance, hypertension, hyperlipidemia, and cardiovascular disease.

In this cross-sectional, retrospective observational study researchers set out to see if a threshold concentration exists for 25(OH)D levels in regards to non-bone endpoints. Researchers further examined the relation between 25(OH)D and race-specific normal ranges to see if a difference exists. Participants in this study included 239 sedentary, postmenopausal women without diabetes who were considered either overweight or obese (average BMI: 33; IQR 29.3 to 35.8). The average age of study participants was 59.7 years (IQR 54 to 64). Of study participants 83 were African American and 156 were Caucasian.

After collecting data researches using piecewise linear regressions to look for threshold effects in the association among 25(OH)D and the following variables: plasma lipids, glucose, insulin, homeostasis model assessment of insulin resistance, insulin-like growth factor-1, parathyroid hormone (PTH), aerobic fitness, body composition, subcutaneous abdominal and visceral fat, and blood pressure.

The percentage of participants with impaired fasting glucose did not differ significantly by race (African Americans 30%, Caucasians 28%; P < 0.76) or impaired glucose tolerance (African Americans 43%, Caucasians: 36%; P < 0.29). Significant inverse predictors of 25(OH)D concentration included BMI, waist circumference, fat-free mass, percentage fat, visceral fat area, and the ratio of visceral fat to total abdominal fat. Aerobic fitness (VO2max) was found to be directly related to 25(OH)D. No relationships between 25(OH)D levels and blood pressure, IGF-1 (P< 0.071), LDL-C or total cholesterol were found – with the exception of triglycerides.

Bivariate scatter grams of 2-h plasma glucose concentration, fasting insulin concentrations, and insulin resistance plotted against 25(OH)D suggested the presence of a critical 25(OH)D concentration. No evidence was found to suggest race-specific 25(OH)D concentration.

Results from this study suggest a threshold effect of 25(OH)D on glucose–insulin metabolism such that 25(OH)D concentrations <26 mcg/L are inversely associated with outcome and concentrations ≥26 mcg/L are unrelated to outcome in overweight and obese black and white postmenopausal women. While the associations found in this study are interesting, a large, prospective interventional study is needed to confirm the existence of a 26 mcg/L threshold for improving glucose homeostasis and insulin sensitivity.

Additional studies are needed to confirm that these results hold true in other patient populations and sub-populations.

Practice Pearls:

  • Multiple associations between Vitamin D levels and non-bone endpoints have been found over the years however a threshold vitamin D level remains unknown – even if one exists
  • A 25(OH)D threshold level ≥ 26 mcg/L may potentially be associated with improvements in glucose homeostasis and insulin sensitivity – regardless of African or Caucasian race/ethnicity
  • Further studies are needed to confirm these findings and possible clinical implications

Sorkin JD, Vasaitis TS, Streeten E, Ryan AS, Goldberg AP. Evidence for threshold effects of 25-hydroxyvitamin d on glucose tolerance and insulin resistance in black and white obese postmenopausal women. J Nutr. 2014;144(5):734-42.