Banishing diabetes with bypass?

PHILADELPHIA—Gastric bypass surgery is an effective option for many people seeking to lose weight or control their weight gain when other options have failed. But this surgery option can also lead to remission for individuals with type 2 diabetes mellitus (T2DM), and a new study out of Nanjing University has uncovered how gastric bypass helps beyond weight loss. The results were published in a paper titled “Gastric Bypass Surgery Reverses Diabetic Phenotypes in Bdnf-Deficient Mice,” which was published in The American Journal of Pathology.

 

The research—led by lead investigator Dr. Xiang Gao of State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute and the Collaborative Innovation Center of Genetics and Development, Nanjing University—was conducted in a T2DM mouse model that can mimic key symptoms of the disease, including insulin resistance, high blood levels of lipids, metabolic inflammation and obesity. Specifically, the animals in this mouse model type have a genetic mutation in brain-derived neurotrophic factor (Bdnf) that leads to Bdnf deficiency. Bdnf is part of the neurotrophic family of growth factors and plays a role in regulating brain function and metabolic balance.

 

“Our findings suggest that Bdnf deficiency-induced diabetes can be reversed by DJB surgery in mice, which has potential for the treatment of diabetes in humans,” stated Dr. Gao.

 

As it turns out, bypass surgery reversed the metabolic abnormalities in diabetes patients without altering Bdnf expression. In addition to improved glucose tolerance and insulin sensitivity, less fat accumulation was seen in the liver and white adipose tissue. Following surgery, the mice achieved insulin sensitivity within two weeks after surgery, and it was maintained for at least eight weeks. Six weeks after surgery, oral glucose tolerance in the treated mice was significantly lower than in the mice that had had a fake operation and was similar to levels seen in untreated controls.

 

The team also found that while bypass surgery improves both glucose tolerance and insulin sensitivity, those improvements happened in conjunction with changes in gut microorganisms as well.

 

“Our research showed that duodenum-jejunum gastric bypass (DJB) surgery may be applied to cure diabetes of both genetic (mutation) and environmental (diet-induced) origin,” Gao noted in a press release. “We found that DJB surgery induced gut microbiota alterations, which may be the key reason for diabetes remission after bariatric surgery. Our data indicate that suppressed inflammation is the result, not the cause, of diabetes reversal in these genetically modified mice.”

 

Upon examining the bacteria and microorganisms in the guts of mouse models before and after bypass surgery, and in comparison with the control group, Gao and his team saw a decrease in pathogenic bacteria and an uptick in beneficial microflora that coincided with the beginning of better glycemic control. Though these are promising results, Gao remarked that “More mechanistic studies of gut microbiota alterations after bypass surgery are needed to explain how different families of microbiota may regulate nutrient metabolism in the host.”

 

Changes were also seen in inflammation levels as well. Inflammation, particularly in white fat tissue (the 'bad' kind of fat) and the liver, is believed to play a role in both obesity and T2DM. Eight weeks out from surgery, the mice who had received gastric bypass presented with significant reductions in inflammatory indicators in the liver and fat tissue; however, post-surgical anti-inflammatory effects took place after insulin sensitivity improved.

 

This work was supported by the Ministry of Science and Technology of China, National Natural Science Foundation of China, and the Natural Science Foundation of the Jiangsu Higher Education Institutions of China.