VANCOUVER – Patients with type 2 diabetes mellitus who lose weight after bariatric surgery experience a reduction in pancreatic triacylglycerol that is not seen in similarly treated nondiabetic individuals, according to a new study that sheds more light on the etiology and reversibility of this disease.
Dr. Roy Taylor and his colleagues performed specialized magnetic resonance imaging in 18 patients with diabetes and 9 matched control patients with normal glucose tolerance, all of whom underwent bariatric surgery.
Dr. Roy Taylor
Despite similar overall weight and fat loss in the diabetic and control groups at 8 weeks after surgery, pancreatic triacylglycerol had fallen by 18% in the former – corresponding to loss of about 0.6 g of fat from the organ – but remained essentially unchanged in the latter, he reported at the World Diabetes Congress.
The findings lend further support to the twin cycle hypothesis of type 2 diabetes, maintained Dr. Taylor, who is a professor with the Institute of Cellular Medicine, Department of Diabetes & Metabolism, Newcastle upon Tyne, England.
According to this hypothesis, positive caloric balance and pre-existing insulin resistance set up dual reinforcing vicious cycles, whereby fat accumulates first in the liver and then in the pancreas, including the islets (Diabetologia. 2008 Oct;51:1781-9). Chronic exposure of beta cells to fat ultimately leads to reduced acute secretion of insulin, contributing to elevated plasma glucose levels.
“Weight loss over 8 weeks brings about loss of pancreatic triglyceride specifically in type 2 diabetes,” he concluded of the study. “[I]t is likely that type 2 diabetes is caused by less than 1 g of fat in the pancreas.”
One session attendee wondered about the role of initially elevated insulin levels in the development of type 2 diabetes. “Do you have any data that reducing insulin levels, not through weight loss or hypocaloric diet, can do the same thing?” he asked.
“Yes, the pre-existing raised insulin levels will be a vital part of the genesis of type 2 diabetes,” Dr. Taylor replied. “Are there other ways to reducing that? Well, I have to say that I don’t know any better way of reducing plasma insulin than weight loss. It has a profound effect: the insulin levels come down entirely into the normal range. If there was some other clever way of doing it, we would expect that to help. But in the practical world, I think we are left with weight loss as the most likely way ahead.”
Another attendee wondered whether the change in pancreatic triacylglycerol was an epiphenomenon. “If you looked at some other tissue and measured triglycerides in the kidney or the heart, would you see a similar relationship? Or is there a way to show that this is actually producing a change in insulin secretion independent of the triglyceride change itself?” he asked.
“I think the clearest data come from the in vitro studies where we can manipulate the islets and show that it will produce the effect,” Dr. Taylor replied, additionally pointing to a recent study in mice in which knocking out fatty acid receptors specifically in the pancreas stopped the development of diabetes in response to obesity (Nat Med. 2015 Feb;21:173-7).
“So I think we have a clear biological model that will be difficult to show in humans. But I would suggest that in view of the totality of the evidence, it’s now beyond a reasonable doubt that we are looking at a causal effect,” he said.
Giving more background to his study, Dr. Taylor noted that previous research has shown that as pancreatic fat content declines in diabetic patients, insulin secretion normalizes (Diabetologia. 2011 Oct;54:2506-14).
“But critics pointed out that if people lose substantial weight, well, of course the fat in the organ will go down. It will happen in anyone, won’t it?” he said. “Well, if it happened only in people with diabetes, the causal relationship would be very strong. If on the other hand it happened in anyone, then perhaps it is a coincidence.”
The patients studied had diabetes for about 7 years, on average. They were matched for age, weight, and sex with control patients having normal glucose tolerance. All had Roux-en-Y gastric bypass surgery.
The investigators performed in-phase, out-of-phase magnetic resonance imaging before and 8 weeks after surgery to quantify the amount of triacylglycerol in the patients’ pancreas and liver.
Results reported at the meeting and simultaneously published (Diab Care. 2015 Dec 1. doi: 10.2337/dc15-0750) showed that after surgery, the control and diabetic groups had a similar reduction in weight (12.8% and 13.6%) and fat mass (11.3 and 13.6 kg).