Type 1 diabetes

Mitochondria the clue to diabetes complications

Adolescents with type 1 diabetes who are at high risk for complications such as cardiovascular, kidney and eye disease also exhibit evidence of mitochondrial dysfunction.

The problem, according to Professor Josephine Forbes from the Glycation and Diabetes Complications Research Group at Mater Research in Brisbane, is it’s hard to know what comes first.

Speaking ahead of the Australasian Diabetes Congress, Professor Forbes told the limbic her team was currently looking at kidney function in people with pre-diabetes and siblings of people with type 1 diabetes for exactly that reason.

“We are trying to understand whether they already have some evidence of mitochondria misbehaving or if they are just more susceptible to developing that when they get diabetes.”

“Either of those options are equally feasible, or both. We don’t really know.”

Professor Forbes said a study of adolescents from the Mater Young Adults Health Centre – a transitional care clinic for 15-25 year olds – showed the young people at high risk of kidney disease were the same patients with mitochondrial dysfunction.

“Your mitochondria are essentially your body’s power stations and we certainly know they are important for things like movement, such as a heart beat. But it is perhaps quite unappreciated that the other sites that are susceptible to complications of diabetes, such as the kidney and the retina, also require a lot of energy.”

She said people with mitochondrial disease often have kidney involvement, cardiovascular disease and diabetes.

“And in our pre-clinical studies we know that if we can manipulate a mitochondrial gene, we can actually cause kidney disease without getting those other manifestations until later.”

“Perhaps, cardiovascular disease, kidney disease and eye disease actually start much earlier than we thought in people with type 1 diabetes.”

Professor Forbes said the 2017 AdDIT study, which unsuccessfully trialed ACE-inhibitors and statin therapy in adolescents with type 1 diabetes, showed how difficult it was to intervene early to prevent known complications.

“Both of those interventions were unsuccessful and that’s perhaps not surprising because these are young people who don’t have high blood pressure; they don’t have a poor lipid profile.”

“And so I guess we are back to the drawing board in some ways although we know that we have to do something. This mitochondrial dysfunction we have identified is perhaps another potential target.”

She said they were currently working with a biotech company with a therapy that targets mitochondria.

“And this is being tested in other applications already, in humans, in Phase 2 trials, and we are hoping we might be able to repurpose this drug and test it in these young patients.”

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