Genes play a role...

An interesting study from the Joslin Diabetes Centre in the USA. They've been studying those who have survived type 1 diabetes for 50+ years, and it looks like genes play a HUGE role in the development (or not) of complications.

May, 2007

In the three years since the start of the second phase of the Joslin 50-Year Medalist study, we have studied over 275 Medalists who have traveled to Joslin. In addition, we are scheduled to study another 150 Medalists in the last year of this study. To those who have already participated, we would like to thank you for all your efforts and help. For those of you who are scheduled to come during the next few months, we are looking forward to meeting you and learning from you.

In the following, I will provide a brief summary of the results that we have obtained thus far. In the first phase of the study, which took place three years ago, we asked many of you to fill out an extensive questionnaire and provide some laboratory data from your doctor. The results from these questionnaires and lab results provided the very interesting finding that close to 50% of you appear to have escaped complications which occur in almost all diabetic patients by 30 years duration. These complications include eye disease (retinopathy), kidney disease (nephropathy) and nerve disease (neuropathy). Further, we have found that both genetic and metabolic factors are important in the prevention of complications in type 1 diabetic patients.

The results showed that as a group, Medalists have controlled their glucose very well for many years. In addition, hemoglobin A1c, a measure of chronic glucose control, does not seem to correlate with the various complications described above. This means that the long survival of Medalists is due to both their own efforts in controlling diabetes and their genes, which protect them from the adverse effects of elevated glucose levels. These are very exciting findings which will be published in the journal *Diabetes Care* in the next few months.

In the second phase of the study, we are bringing many of you to Joslin and examining the status of your complications with respect to your eye, kidney, nerve and heart function. We are also studying the metabolic changes in your blood and your body's ability to produce insulin. We are also studying your genes in order to determine whether you have typical type 1 diabetes or a different, yet unknown type, and whether your body is still producing auto-antibodies against insulin producing cells found in the pancreas.

Data from over 200 of you have been analyzed and we have made very exciting discoveries. The data showed that most of you have clinical and laboratory findings consistent with patients who have been identified with "typical" type 1 diabetes. We have confirmed the results of the questionnaire to show that the parameters of glucose control such as hemoglobin A1C and glycated albumin do not correlate with the presence of eye, kidney and nerve dysfunction in the Medalists. The eye studies, which took pictures of the back of the eye, showed that about 40% of the Medalists do not have significant eye disease even after 50-80 years of type 1 diabetes. In addition, we also analyzed the lipid or fat profile of blood samples, which showed that many of you have elevated levels of HDL, the good cholesterol that protects people from developing cardiovascular disease.

From a complications point of view, these findings are very exciting since they showed that 40% of the Medalists have factors or genes which have protected them from developing diabetic eye disease. In the next phase of this study, we are planning to perform genetic studies with the hope of detecting genes which can protect all diabetic patients from developing complications. The results are clearly telling us that further genetic studies are needed in order to find these diabetes complication-preventing genes.

In addition to the exciting findings regarding diabetic complications the results from the Medalists have also yielded an unexpected finding regarding your pancreatic functions. Surprisingly. the pancreatas of over 20% of Medalists appear to produce a small amount of insulin. This finding is clearly very important and exciting since it suggests that in some type 1 diabetic patients, the pancreas, which makes insulin, may still be functional after 50-70 years' duration. If this finding can be confirmed, then it raises the possibility that many type 1 diabetics who have fewer years of diabetes may continue to have functional pancreatic tissues that could make insulin. Thus, in the last few months and in the near future, we have/will bring some of the Medalists back to Joslin for further studies to determine whether their pancreatic islets can potentially make insulin. In response to various known stimulations of insulin secretion

In the above, I have summarized the new findings from the Medalist study, which have clearly suggested that we should do the following: 1.) Further genetic studies are needed to determine which genes are present in approximately 40% of the Medalists that are protective factors for preventing blood vessel problems. 2.) New stimulation tests are needed in order to determine whether some of the Medalists still have functional insulin-producing islets after such a long time with type 1 diabetes. 3.) Further collections from new Medalists must be done in order to continue the study and gather more data.