Saturday Morning Research Review – April 30, 2016

Intensive diabetes management can delay development of diabetic complications

by Adam Burrack, PhD

One goal of continuous, careful, management of blood glucose levels is the hope that we are delaying the development of diabetes-related complications. A core tenet of our mission at YOUglycemia is that consistent exercise can serve as a pillar of effective diabetes management. The first systematic, large-scale attempt to study whether improved diabetes management does in fact improve long-term health outcomes relationship existed was the Diabetes Control and Complications Trial in the 1980s. DCCT was designed to test, essentially, whether more effort put into diabetes management correlated with (1) improved HbA1c measurements, and (2) long-term health benefits.

The editors of the journal Diabetes Care recently produced a compilation of long-term health outcome results from this study. These reports in demonstrate delay of each of the 4 major categories of complications from diabetes, long-term (ie for >30 years of follow-up), following a 5-ish year period of “intensive diabetes management” during the DCCT trial. As a refresher, here is a run-down of the 4 major categories of diabetic complications. First, cardiovascular disease. Similar to Americans in general, >50% of people with type 1 diabetes will die from CVD. Unfortunately, T1D accelerates and exacerbates CVD, for reasons which are not entirely understood. Second, retinopathy: diabetes is a leading cause of blindness due to proliferative retinopathy. As such, all people with type 1 diabetes are advised to get yearly eye exams (especially after 10 or more years of T1D) to assess the presence or progression of retinopathy. Third, peripheral neuropathy, or nerve damage, is a result of long-term poor blood glucose level management. This complication can be particularly debilitating: loss of nerve function can lead to loss of sensation in the lower legs, poor wound healing, and in worst-case scenarios, lower-leg amputation. Fourth and last, diabetes is a leading cause of kidney disease leading to renal failure and either kidney transplantation or long-term dialysis.

As a reminder, these are worst-case, long-term, poor-management scenarios. The hope with intensive diabetes management was that these complications would be largely mitigated by careful attention paid to blood sugar levels, over years and decades of diabetes management. It is a critical point that there is no such thing as perfect diabetes management – everyone will have ups and downs in their blood sugar levels. In my opinion (as a 31-year T1D patient) is that much of the “game” with diabetes is psychological: no failure with T1D is permanent, and neither is any success. Literally every day provides another chance to learn more about how your body works, to improve management of your diabetes.

For discussing the major diabetic complications, we need to discuss one key bit of physiology. Physicians and scientists believe some of the pathology of diabetic complications results from the formation of advanced glycation end products – which means the extra sugar in the circulation which defines diabetes can stick to things like the cells lining the blood vessels (called endothelium), which is part of the pathway setting in motion events leading to the above complications, in particular cardiovascular disease. To cut to the chase: AGEs promote inflammation, and as such promote insulin resistance. In a cruel twist of fate, AGEs are cleared by the kidneys, as is excess sugar, putting exponentially more stress on the individual filtration units of the kidneys, nephrons.

Another key player in development of diabetic complications is the polyol pathway. Long story short, excess sugar in the blood can directly affect nerves and the retina, since these tissues take glucose into themselves regardless of insulin. In context of high blood sugar levels, these tissues (1) take in sugar, which leads to (2) formation of reactive oxygen species, and (3) perturbs the normal production of nitric oxide, a key molecule which promotes dilation of blood vessels. These effects combine to yield unfavorable outcomes for nerves, kidney cells, and the retina.

To the data. 30-year follow-up studies on patients from the DCCT study show lower likelihood – regardless of diabetes management in the intervening 30 years – of cardiovascular disease, decreased incidence of diabetic retinopathy, decreased incidence of diabetic neuropathy, and improved outcomes in long-term kidney function.

These are all great outcomes for the individuals with T1D in the study, and have several important implications for all of us with T1D. First, a period of very good diabetes management (6.5 years in the DCCT study) has long-lasting benefits for the entire range of diabetic complications. Second, to minimize the development of diabetic complications, these studies emphasize the imperative to achieve as close to normal BG level control as possible as early as possible following T1D diagnosis. To conclude, diabetic complications are definitely NOT an inevitable consequence of long-term diabetes. The better our diabetes management, the less likely we are to develop any of the 4 major diabetic complications.

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