Higher Vitamin D3 Levels Link to Less Insulin Resistance

Marlene Busko, for Medscape

March 24, 2022

Researchers published the study covered in this summary on Research Square as a preprint that has not yet been peer reviewed.

Data from five sequential National Health and Nutrition Examination Survey (NHANES) reports using US population samples in 2009-2018 showed each 1-unit increase in serum levels of vitamin D₃ (25-hydroxyvitamin D₃) (measured as nmol/L) was significantly associated with an 11% lower risk of developing insulin resistance.
This association between higher serum vitamin D₃ levels and a reduced risk for insulin resistance was strongest in people with a body mass index (BMI) of 24 to 28 kg/m² (overweight). The association was weaker in people with BMIs below and above this range.

Vitamin D₃ deficiency is common worldwide.
The findings further strengthen the understanding of insulin resistance in the context of widespread vitamin D₃ deficiency and suggest that vitamin D₃ supplementation might reduce insulin resistance and prevent development of diabetes in the general US population.
Previous studies examining the connection between vitamin D₃ and insulin resistance have focused on patients with diabetes, whereas this study used data from the general US population.
The authors say this is the first study to find that BMI influences the strength of interaction between vitamin D₃ levels and insulin resistance.

Researchers analyzed data from 49,694 participants in five consecutive NHANES cycles from 2009 to 2018, and from this cohort they examined data from 2746 people age 18 and older; had data for vitamin D₃, fasting insulin, and fasting glucose; did not have diabetes, hypertension, hypercholesterolemia, or hyperuricemia; and met several other inclusion and exclusion criteria
They estimated insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR), which is equal to fasting insulin (μU/mL) times fasting glucose (mmol/L) divided by 22.5.
Insulin resistance was defined as HOMA-IR ≥ 2.6 and the absence of IR as HOMA-IR < 2.6.

862 participants had insulin resistance and 1884 participants did not have insulin resistance.
Participants were an average age of 35 years old, and 44% were men.
Median vitamin D₃ level, measured by liquid chromatography-tandem mass spectrometry, was 50.9 nmol/L in those with insulin resistance and 58.5 nmol/L in those without insulin resistance.
In the fully adjusted multivariable model, patients had a significant 11% lower rate of prevalent insulin resistance for each 1-unit increase in serum vitamin D₃.

The cohort examined did not include enough nonsmokers to determine whether smoking affects the link between insulin resistance and vitamin D₃ levels.
The study excluded people with hyperlipidemia, hyperglycemia, and hyperuricemia, and so the findings are not generalizable to the entire US population.
It remains unclear how genetics might impact the relationship between vitamin D₃ levels and risk of insulin resistance, as this was not included as part of the analyses.
HOMA-IR does not provide reproducible nor fully accurate measurements of insulin resistance.