The Role of Genetics in Diabetes Complications

Almost 30 years ago research found that chronic hyperglycemia (high blood glucose), as well as the length of time a person has diabetes, are associated with the development of complications. However, researchers have recently discovered that there is more to the story.

Someone can have an HbA1C of 10 or 11% their entire life without developing many diabetes complications. On the other hand, some people with consistent HbA1Cs of 6% since diagnosis develop numerous complications. This may seem counterintuitive given the fact that we are all told to keep our blood glucose in the target range as much as possible in order to prevent and/or delay complications.

Additional research and data have accumulated to suggest that genetics has a role in the development of complications—but how and why is still unclear.

Genetics

Studies have found people in the same family who have diabetes develop the same type of complications but not other types, so this suggests genetic involvement. This is true for both microvascular (e.g., eye, kidney and nerve diseases) and macrovascular (stroke, heart disease, peripheral disease/reduced blood flow in extremities) complications.¹ This might partially explain, for example, why only one-third of people with diabetes and not everyone, eventually develop kidney disease.²

In addition, researchers have been pinpointing specific genes and locations on these genes that are associated with certain complications like eye, kidney, or heart disease. New mechanisms by which the diabetes-related complications develop have also been discovered.³ More research is showing that a person’s behaviors and environments (epigenetics) such as exercise or diet, interact with genetic factors to develop complications.^4,5

Historically there has been focus on and progress in researching treatments for diabetes as well as the genetics of type 1 and type 2 diabetes. In comparison, there has been significantly less research on the genetic basis of diabetes-related complications. More research and larger studies are planned that will hopefully help to identify which specific complications an individual is at risk for, assist in creating new ways of detecting complications earlier, and aid in the development of new treatments for people with these diabetes-related complications.⁶

What we know

For now, until we understand more about the genetics of complications, we know that chronically high blood glucose and duration of diabetes (the longer a person has diabetes) play important roles in the development of complications. But, don’t despair—we also know that:

• More intensive diabetes management (keeping blood glucose levels as close to the target range as possible) greatly lowers a person’s chance of developing eye, kidney, and nerve diseases as shown in the landmark studies—the Diabetes Control and Complication Trial (DCCT) that included people with type 1 diabetes and the United Kingdom Prospective Diabetes Study (UKPDS) that included people with type 2 diabetes.^7,8 Even in genetic-risk studies, high blood glucose plays a central role in the development and progression of complications.⁵
• There are long-term benefits of intensively managing blood glucose and doing it as early as possible to reduce the future development of diabetes-related complications.⁸
• Keeping blood glucose as close to the target range as early as possible also lengths lifespan, so people with diabetes can live long and healthy lives.⁸

Although we need to learn a lot more about complications, we do know that we have an important role in our long-term health. By adopting a healthy lifestyle (eating healthy, exercising, stopping smoking, limiting alcohol intake, etc.), going to recommended appointments for screening and managing our blood glucose as best we can (keeping our blood glucose as close to our target range as possible), we can help to prevent and/ or delay developing and potentially slow progression of complications.

1. Alkayyali S, Lyssenko V. Genetics of diabetes complications. Mamm Genome. 2014;25(9-10):384-400. doi:10.1007/s00335-014-9543-x
2. Liu R, Lee K, He JC. Genetics and Epigenetics of Diabetic Nephropathy. Kidney Dis (Basel). 2015;1(1):42-51. doi:10.1159/000381796
3. Dahlström, E., Sandholm, N. Progress in Defining the Genetic Basis of Diabetic Complications. Curr Diab Rep. 2017;17:80 doi: 10.1007/s11892-017-0906-z
4.Villeneuve LM, Natarajan R. Epigenetics of diabetic complications. Expert Rev Endocrinol Metab. 2010;5(1):137-148. doi:10.1586/eem.09.54
5. Ma RC. Genetics of cardiovascular and renal complications in diabetes. J Diabetes Investig. 2016;7(2):139-154. doi:10.1111/jdi.12391
6. Implications of the Diabetes Control and Complications Trial. American Diabetes Association Diabetes Care. 2003;26(1):s25-s27. doi: 10.2337/diacare.26.2007.S25
7. American Diabetes Association: Implications of the United Kingdom Prospective Diabetes Study (Position Statement). Diabetes Care. 2002,25(1): S28–S32. doi: 10.2337/diacare.25.2007.S28
8.David M. Nathan, for the DCCT/EDIC Research Group. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study at 30 Years: Overview. Diabetes Care. 2014,37(1):9-16. doi: 10.2337/dc13-2112

Educational content related to diabetes complications is made possible with support from Allergan, an active partner of Beyond Type 1 at the time of publication. Editorial control rests solely on Beyond Type 1.