Two diseases that keep turning up together

Here is a fact that does not get nearly enough attention. People with type 2 diabetes are more likely to develop dementia, including Alzheimer's disease, than people without it. The paper behind this series cites research putting the extra risk at about 60%.

That is not a small nudge. It is one of the more consistent links in modern medicine, and nobody has fully explained it.

The paper opens with the scale of the diabetes side of the problem. At the time of writing, about 463 million people worldwide had diabetes, a number expected to reach 700 million by 2045. Diabetes was linked to an estimated 4.2 million deaths a year among adults aged 20 to 79, around 11% of all deaths in that group.

Put those two facts together, rising diabetes and a strong link to dementia, and you get a problem that will land on a great many families over the next few decades.

What could connect blood sugar and memory?

The authors are honest that the molecular link between type 2 diabetes and Alzheimer's is still unknown. But they have a strong suspect, and it is the same one that runs through every series on SS-31: the mitochondria.

Mitochondria are the small power plants inside your cells. They turn fuel into energy, and when they struggle, they leak harmful oxygen molecules and the cell starts to suffer.

Mitochondrial problems show up in diabetes. They also show up in Alzheimer's. The research group behind this paper, led by P. Hemachandra Reddy at Texas Tech University Health Sciences Center, has spent years arguing that damaged mitochondria might be one of the shared early events that link the two.

If high blood sugar damages mitochondria throughout the body for years before memory problems appear, then understanding and protecting those mitochondria might matter long before anyone gets a dementia diagnosis.

Why study the liver?

This is the part that confuses people at first. If the worry is the brain, why look at the liver?

Because the liver is at the centre of how the body handles sugar. It stores glucose, releases it, and works hard to keep blood sugar steady. It is packed with mitochondria. And in diabetes, the liver is one of the first organs to show strain.

Studying the liver lets the team see what years of high blood sugar does to mitochondria in a tissue that is directly in the firing line. It is part of a larger programme. The same group had already published a study on the pancreas of the same mice, and this paper extends that work to the liver.

Where SS-31 comes in

SS-31 is a short peptide designed to slip into cells and settle on the inner membrane of the mitochondria. It is often called a mitochondria-targeted antioxidant. The paper notes that the Reddy group had already reported protective effects of SS-31 on mitochondria in models of type 2 diabetes, Alzheimer's disease and Huntington's disease.

So the question in this study is direct. If high blood sugar damages liver mitochondria in diabetic mice, can four weeks of SS-31 reverse some of that damage?

What the study looked at

In short, the team compared three groups of mice:

  • Normal, non-diabetic mice
  • Diabetic mice given a dummy injection
  • Diabetic mice given SS-31

They then measured, in the liver:

  • Hydrogen peroxide, a harmful oxygen molecule
  • Damage to fats in cell membranes
  • ATP, the energy molecule the mitochondria produce
  • The genes and proteins that control how mitochondria split, merge and multiply
  • What the liver tissue looked like under a microscope

The headline is that diabetic mice had clearly damaged liver mitochondria, and SS-31 pushed almost every measure back toward normal.

What this series will cover

Over the next parts we will meet the unusual mouse at the centre of this study, look at three warning signs of struggling mitochondria, get into the surprisingly important balance between mitochondria splitting and merging, look at how cells build new mitochondria, see what the microscope showed, and compare the dosing schedule with other SS-31 research.

Then, in the final part, I will point out the one measurement that is conspicuously missing from this paper. It is a big one, and once you notice it you cannot stop noticing it.

Keep in mind throughout: this is a mouse study. It is a useful window into biology. It is not evidence about what SS-31 does in a person with diabetes.

This series discusses a peer-reviewed laboratory study in mice. The results have not been shown in people. Nothing here is medical advice, and SS-31 is discussed for research purposes only.