January 14, 2020

Research continues to reveal new information concerning mechanisms of the diabetes drug metformin and the mineral magnesium’s antidiabetic effects.

A systematic review and pooled study published on November 22, 2019 in Diabetes/Metabolism Research and Reviews affirmed an association between increasing magnesium intake and a lower risk of type 2 diabetes. Furthermore, supplementing with the mineral was found to be associated with improvement of factors relating to glucose metabolism.

Binghao Zhao and colleagues selected 26 articles reporting observational studies that included a total of 1,219,636 men and women for the study of magnesium intake’s effect on diabetes incidence. Participants had no diabetes or insulin usage upon enrollment and were followed for a median of 11.2 years. 11 studies measured magnesium from food alone and 15 measured total magnesium from diet and supplements.

The authors categorized magnesium intake as high or low. When subjects whose magnesium intake was high were compared to those whose levels were low, the risk of developing type 2 diabetes was 22% lower. For each 100-milligram increase in daily magnesium intake, the risk of diabetes was lowered by 6%.

For their investigation of the effects of magnesium supplementation on glucose metabolism, 26 randomized, controlled trials were selected that included a total of 1,168 participants who had type 2 diabetes or were at high risk of the disease. Supplementing with magnesium was associated with improvements in fasting plasma glucose, two hour oral glucose tolerance test results, fasting insulin levels, insulin resistance, triglycerides, and systolic and diastolic blood pressure. “Interestingly, magnesium supplementation had a positive effect on HDL cholesterol levels, and it should be acknowledged that supplementation may have long-term effects on glucose metabolism and lipid levels,” Dr Zhao and associates remarked.

“For type 2 diabetes prevention, current evidence supports the recommendation for individuals to increase magnesium-rich diet consumption or supplement with magnesium,” they conclude. “Such alternatives targeting a reduction in public health and economic burdens will not only guide policy decisions but also possibly launch a global dietary reform.”

Other research has found new mechanisms of action for the front-line diabetes drug metformin, which is being investigated for its potential role in slowing aspects of aging. A known mechanism of metformin is that of activating AMP-activated protein kinase (AMPK), an intracellular enzyme that reduces blood glucose by promoting energy utilization; however, the exploration of additional biochemical pathways has been limited. In a study published in the December 3, 2019 issue of Cell Reports, Benjamin D. Stein and colleagues investigated metformin-induced signaling in mouse liver tissue. They discovered that metformin activates two kinases (proteins that transfer phosphate groups), known as protein kinase D (PKD) and MAPKAPK2 (MK2), which are activated by stress.

"We never imagined these two kinases would have anything to do with metformin," commented corresponding author Reuben J. Shaw, who is the director of the Salk Institute’s Cancer Center. "The results broaden our understanding of how metformin induces a mild stress that triggers sensors to restore metabolic balance, explaining some of the benefits previously reported, such as extended healthy aging in model organisms taking metformin. The big questions now are what targets of metformin can benefit the health of all individuals, not just type 2 diabetics."

These recent findings may be promising for those with diabetes or prediabetes, and for all of us who want to live longer.