Vitamin D Shows Pancreatic Dysfunction Link in T2D With Obesity

Marlene Busko, for Medscape

May 02, 2022

Researchers published the study covered in this summary on as a preprint that has not yet been peer reviewed.

Key Takeaways

  • Levels of 25-hydroxyvitamin D (25[OH]D), also known as vitamin D3 and the major circulating form of vitamin D, inversely associated with levels of glucagon (secreted by pancreatic islet α-cells) and connecting peptide (C-peptide; secreted by pancreatic islet β-cells during insulin production) in 4670 Chinese patients with type 2 diabetes and abdominal obesity, in a cross-sectional study.

  • Higher 25(OH)D levels associated with better homeostasis between pancreatic α-cells and β-cells in patients who had type 2 diabetes for a short time as well as abdominal obesity.

Why This Matters

  • Most research into the effect of 25(OH)D on pancreatic islet function in type 2 diabetes has focused almost entirely on pancreatic β-cells (which secrete insulin), even though vitamin D-binding proteins are present in pancreatic α-cells as well as β-cells.

  • Higher levels of 25(OH)D may negatively influence glucagon secretion from islet α-cells, and decreased glucagon may in turn reduce insulin secretion from islet β-cells. In short, the findings suggest that 25(OH)D might modulate intra-islet crosstalk between α- and β-cells.

  • If confirmed and expanded on in future investigations, the current findings could potentially lead to new approaches for treating disorders of glucose metabolism.  

Study Design

  • As part of the prospective, cross-sectional Environmental Pollutant Exposure and Metabolic Diseases in Shanghai study that began in 2018, the researchers identified 4670 patients with type 2 diabetes and complete data from a cohort of 5827 patients who were aged 23-99 years when they were seen at healthcare centers in Shanghai, China.

  • Participants completed a detailed questionnaire and the researchers determined the participants' height, weight, waist circumference, and blood pressure. 

  • Blood samples from participants underwent analysis for a range of components that included 25(OH)D, C-peptide, glucagon, fasting insulin (FINS), and fasting plasma glucose (FPG).

  • The researchers calculated β-cell function (HOMA-β) and insulin resistance (HOMA-IR) based on the Homeostasis Model Assessment for Insulin Resistance.

  • The researchers divided the participants into quartiles based on their 25(OH)D levels, and they also divided participants into those with and without abdominal obesity.

Key Results

  • The lowest 25(OH)D quartile had levels of ≤ 30.79 ng/mL, whereas the highest quartile had levels of ≥ 48.92 ng/mL

  • Compared with participants in the lowest 25(OH)D quartile, those in the highest vitamin D quartile were younger and more likely to be male.  

  • Among patients with type 2 diabetes without abdominal obesity, 25(OH)D levels inversely and significantly associated with fasting plasma glucose, A1c, glucagon, and HOMA-β levels, after adjusting for multiple variables.

  • Among patients with type 2 diabetes with abdominal obesity, 25(OH)D levels inversely and significantly associated with A1c, glucagon, fasting insulin, fasting C-peptide, and HOMA-IR levels, after adjusting for multiple variables.

  • In patients with type 2 diabetes for a short time plus abdominal obesity, those with higher 25(OH)D levels had a lower ratio of glucagon to C-peptide (that is, they had a better homeostasis between islet α-cells and β-cells) than those with lower 25(OH)D levels.


  • This was a cross-sectional study, so it cannot determine whether 25(OH)D causes islet function homeostasis.

  • The study lacked data on, and hence could not adjust for, use of vitamin D supplements nor for variations in sun exposure.

  • The researchers did not measure postprandial C-peptide and glucagon levels, so it remains unknown whether the association between 25(OH)D and postprandial islet function homeostasis also extends to improved A1c levels.


  • The study did not receive commercial funding.

  • The authors had no disclosures.

This is a summary of a preprint research study , "25-hydroxyvitamin D is associated with islet function homeostasis in type 2 diabetes patients with abdominal obesity diabetes," written by researchers at Shanghai JiaoTong University School of Medicine on Research Square, provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on

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