Vitamin D Repletion Boosts Insulin Sensitivity in Prediabetes

Vitamin D repletion reduces adipose tissue fibrosis and improves insulin sensitivity in persons at risk for diabetes mellitus (DM), according to a new study.

Vitamin D reduces fibrosis in various tissues by inhibiting profibrotic processes and collagen synthesis. “When fat tissue is less inflammatory, the liver is more responsive in overweight, middle-aged patients bordering on diabetes who have insulin resistance,” Meredith Hawkins, MD, Professor of Medicine at Albert Einstein College of Medicine, Bronx, New York, told ConsultantLive.

Einstein researchers conducted a study to see whether vitamin D repletion could reduce adipose fibrosis and improve insulin sensitivity. They performed 2-step euglycemic, hyperinsulinemic pancreatic clamp studies in 9 obese, insulin-resistant patients. The patients, median age 43 years, had an average body mass index of 34 kg/m² and homeostasis model assessment-estimated insulin resistance of 5.1, before and after normalizing vitamin D levels with more than 30 ng/mL of oral vitamin D3.

Vitamin D repletion reduced subcutaneous adipose tissue fibrosis, reported Akankasha Goyal, MD, at the American Diabetes Association’s 74th Scientific Sessions in San Francisco (Abstract 90-OR). Gene expression of collagen I, collagen V, and HiF-1-alpha in whole fat decreased significantly, and collagen immunofluorescence decreased by 48%.

In addition, vitamin D repletion reduced adipose inflammation, with decreased expression of tumor necrosis factor alpha and PAI-1 in whole fat. It also significantly decreased expression of interleukin 6, inositol, and PAI-1by adipose macrophages. “These findings were associated with 34% greater ability of insulin to suppress endogenous glucose production. Glucose uptake was unaffected,” Dr Goyal said.

In conclusion, Dr Goyal said: “Vitamin D repletion reduced adipose tissue fibrosis in concert with improved hepatic insulin sensitivity and reduced adipose inflammation in obese patients. Correcting Vitamin D deficiency in susceptible individuals could have considerable metabolic benefit.”

Dr Hawkins noted that patients with normal glucose metabolism show no benefit with vitamin D replenishment, but “it can make a difference for those who are insulin resistant. We can’t show that vitamin D replenishment prevents diabetes, but people at risk for diabetes show a benefit.”

She added: “Our simple but intensive study looked at insulin resistance in muscle and liver. When we drilled down to the metabolic level, we found there really is a benefit.”

Researchers have been investigating the role of fibrosis in easing insulin resistance. “In people who put on weight, fat spills into the liver. Fibrosis is linked to inflammation of fat as inflammatory cells go into fat. It’s as though the fat is fighting off an infection,” Dr Hawkins said. “If we give vitamin D, we see fat tissue is both less fibrotic after a few months and less inflammatory, and the patient is less insulin sensitive.”

The next step in this research is to enroll patients with DM into a clinical study. “In diabetes, the disease may have advanced too far. We still advocate vitamin D replenishment for prediabetes,” Dr Hawkins said.

The key is to normalize vitamin D levels. “We replaced vitamin D to normal levels of 30 ng/mL and saw benefit. When we pushed replacement to 50 ng/mL, we saw no further benefit,” she said.

Dr Hawkins recommends that for those who are at risk for DM, clinicians should “check their vitamin D levels and maintain normal levels.”