Immune From Diabetes Complications

Why do some people develop terrible complications from diabetes, while others skate through with no complications at all? Is there such a thing as immunity from complications, and if so how can you get that immunity for yourself?


Unfortunately, nobody knows the answer to those questions, and until now, few have even looked into them. We know from the Diabetes Control and Complications Trial (DCCT) and from other studies that blood glucose control makes a big difference in complications of diabetes. But there is much more to the story.

In the DCCT, and the long-term follow-up study called EDIC (Epidemiology of Diabetes Interventions and Complications), people with Type 1 practicing “intensive blood glucose control” reduced diabetic kidney disease by 50%, heart attacks by 57%, nerve disease by 60%, and eye disease by 76%. Pretty good, but what about the 25% to 50% of intensive control subjects who got the complications anyway? And what about the 10% to 15% of people with Type 1 who never seem to get severe complications, without practicing intensive control?

You would think such a basic question — where do complications come from — would have received more attention. People with diabetes certainly care. On the Web site TuDiabetes, a reader with Type 1 asked, “I [have had diabetes for over 38 years] with no complications. [For many years] my control was impossible. Why has nothing untoward happened after it was drilled into me that [complications] and death would soon follow?”

Now Swedish scientists are finally starting to look at this basic question. Valeriya Lyssenko, MD, PhD, and Peter Nilsson, MD, PhD, both from Lund University Diabetes Center, are conducting the PROLONG (PROtective Genes in Diabetes and LONGevity ) study, looking at Swedes who have had diabetes for more than 30 years, half of them without complications. They will be compared to others who have had diabetes less than 15 years and have already developed major complications.

According to the Lund University researchers, “Despite decades of intensive research on diabetes complications, the fundamental mechanisms are not yet fully known. Neither is it possible to prevent or treat the damage to the blood vessels that affects the majority of diabetics.”

At least scientists are finally looking. Another study at Joslin Diabetes Center in Boston is following people who have had Type 1 for over 50 years, to find out what keeps them complication-free, or close to it.

What’s Known About Complications?
According to Dr. Nilsson, complications arise because “The blood vessels and other organs of the body become sugar coated and stiff. It is reminiscent of premature biological aging.” I would call that a pretty unsophisticated level of understanding.

They’re starting to learn more at the cellular level, at least in mice. Washington University researchers say that blood vessel damage in diabetes may involve a deficiency of fatty acid synthase (FAS) an enzyme that helps protect blood vessel walls. Mice engineered to lack FAS had a lot of blood vessel damage. People with low insulin production or high insulin resistance also tend to have low levels of FAS.

According to Dr. Lyssenko “About half of these diabetic veterans do not have major complications. Two-thirds of those who have had diabetes for more than 50 years have escaped complications. Clearly they are different and we want to find out what it is that protects them.”

The Lund study participants will answer questions about their lifestyle and diseases they, or their closest relatives, may have. Genetic tests will be analyzed, and close relatives of the participants will also be invited to take part.

How does this research relate to people with Type 2? Scientists at the University of Aarhus in Denmark are wrapping up the first phase of a study of how the immune system affects vascular complications of Type 2. They suspect that “sugar-coating” of blood vessels does not fully explain complications. They think the immune system is involved. “Molecules called PRMs (pattern recognition molecules) in the immune system contribute to a chronic low grade inflammation in diabetic patients,” they write. “Variation in PRM’s… is associated with the degree of … inflammation, and probably also with the prevalence of vascular complications.”

It’s looking more and more like all types of diabetes should be considered inflammatory diseases. Hopefully this will lead to new treatments and paths to prevention, but how does this knowledge apply to self-management? I hope readers have some ideas, but all I can do is refer you back to this article on inflammation from 2009, or this one on anti-inflammatory diets. Other than that, it seems like the best thing you can do is to have good genes, and the second is to keep glucose well controlled. A person concerned about inflammation could certainly take cheap anti-inflammatories such as salsalate or ibuprofen. One could also reduce stress, meditate and relax more, and move one’s body more.

One encouraging note from the Swedes: They have found that “a person who has had diabetes for [over 30 years] without developing complications is unlikely to develop them later in life.” So if you’ve made it that far, things are looking good!

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  • calgarydiabetic

    A true mystery that is not explained by the tightness of the blood sugar control alone. Richard a 50 year veteran suspects that the c-peptide that was contained in the old animal insulin was a protective agent and some diabetics still have some level of their own insulin production with associated c-peptide. If so then the new insulins are no good at protecting from complications.

  • Bob Fenton

    David, Thank you for this post. It is well balanced and explains some things that many people just ignore and then become upset about when they develop a complication. It will be very interesting to see the results of the PROLONG study.

  • Betty Martin

    I can happily say that I’ve been a type 1 Diabetic for 44 years with no major complications. I’m a 72 y/o RN who still sorks in Public Health. I have minor kidney damage because at age 45, I had severe Lupus Nephritis….100mg. of Prednisone for about 7 months plus other major meds. I have had minimal retinopathy. I have not been well controlled, having lows and over treating, causing highs. I’m on the pump for 12 years. I consider myself very fortunate because of excellent health insurance coverage. I would love to take part in a study.
    Betty Martin, New Jersey

  • beenT1/`88

    I asked my endo that very question on my last visit…22 yrs.T1, stuggling to keep any control nevermmind tight ctrl…but I do find myself very fortunate and blessed for not having any complications as yet..1 of my worries is that I`ll wake up one day and all the complications that I most fear will just be there.. I`ve recently started pumping and while control has improved my weight has jumped..this article was a good read

  • Susan Shaw

    Fantastic article. Thanks David.

  • Diane

    What about low dose aspirin daily? Do you think that will help with inflammation as well? I’ve often thought about it. T2 for 8 years.

  • David Spero RN

    Diane, I think low-dose aspirin is worth a try. Studies have found salsalate, another anti-inflammatory similar to aspirin, has benefits for diabetes. It’s prescription, though. I wrote about it here:

  • rosalyn marsh

    I’ve had type 1 for 30 years now, and am now 47. The only problems I have had is flamatory problems such as tendonitis and carpal tunnel syndrome etc. I rebelled for many many years and never checked my sugars, I literally made up the results in the waiting room… Four years ago I became pregnant at 42 and checked my sugars at least 9 times a days, and since having my daughter, I now check every day which is amazing for me! After being pregnant diabetic Rhinopathy and also protein started to show in my urine, it seemed to me that the pregnancy had contributed to me to them start developing complications. My eye doctor said he disagreed the eye problems were as a result of the pregnancy, due to diabetics after 30 years would always have some degree of eye disease? However, since having my daughter, my eyes are improving and the protein now all but gone, so am back to pre pregancy diabetes with No major complications. I realise that I am incredibly lucky, although I have to mention that I have NEVER been on human insulin, and after reading comments about the c-peptide being in the animal insulin, I think I may just stay on it.

    • Richard Vaughn

      I have read that animal insulin produced now does not contain c-peptide.

  • Celsus

    The figures given are wrong, since only one-third of patients living 50 years or more with type 1 diabetes are free of complications, while two-thirds are not. One point not frequently noted is that anyone who has now survived 50 years or more with the disease had to spend at least 20 years as a diabetic before home glucose monitoring was possible, so these patients have not done well or lived long because of strict glucose control, but rather, in spite of a long history of poor control.