LISBON – Exercise was associated with a lower risk of all-cause mortality in patients with type 1 diabetes mellitus, regardless of whether or not they also had chronic kidney disease, according to an analysis of data from a large ongoing population study.

Fully adjusted hazard ratios comparing low versus moderate-to-high amounts of physical activity, intensity, frequency, and duration were a respective 1.63, 2.17, 2.07, and 1.86 in patients without CKD.

The corresponding HRs in patients with comorbid CKD were 1.47, 1.39, 1.90, and 1.49, although only the total exercise amount and frequency were statistically significant in this study group.

“We know that exercise improves blood pressure, improves endothelial function, lowers inflammation and sympathetic [nervous system] load, improves our lipid profile, reduces weight, A1c, and improves insulin sensitivity,” Heidi Tikkanen-Dolenc, MD, of Helsinki University Central Hospital, reported at the annual meeting of the European Association for the Study of Diabetes.

“So far, we know little about exercise and mortality in type 1 diabetes in a prospective setting,” Dr. Tikkanen-Dolenc added. There have been two large studies – the Pittsburgh Study (Diabetes. 1984;33:271-6) and the EURODIAB study (Diabetologia. 2013;56:82-91) – that have been conducted previously. The first showed a benefit of greater participation in team sports and leisure time physical activity (LTPA) in men only, and the second showed a borderline inverse association between a higher amount of LTPA and mortality in both sexes, she said. There are even fewer data specifically in patients with comorbid CKD, although exercise is recommended and appears to be safe, she said.

Dr. Tikkanen-Dolenc and her associates have previously shown that diabetic nephropathy largely accounts for the increased mortality risk in T1DM (Diabetes. 2009;58:1651-8), and that the intensity of exercise rather than the total amount could be important (Diabetologia. 2015;58:929-36). They have also found that high intensity and frequency of LTPA was associated with a decreased risk of cardiovascular events in patients with T1DM (Diabetologia. 2017;60:574-80). Now, they wanted to look more specifically at how LTPA might be associated with mortality in T1DM and also do a separate investigation of what happens when there is concomitant loss of kidney function.

Patients included in the analysis were part of the Finnish Diabetic Nephropathy (FinnDiane) Study, which is a nationwide study being conducted in 90 centers in Finland to look for risk factors and mechanisms behind diabetic complications. To date, the study involves around 5,000 participants, and 2,369 were included in the present analysis. Of these, 310 also had CKD, which was defined by an estimated glomerular filtration rate of 60 mL/min per 1.73 m² or lower.

A previously validated questionnaire was used to measure LTPA. The total LTPA was calculated by measuring the time spent doing an activity by the intensity index expressed in metabolic equivalents (MET). The latter is a widely used unit in exercise research, Dr. Tikkanen-Dolenc said, and gives a measure of the ratio of the metabolic rate during activity to the rate at rest.

Over a follow-up of 11 years, 270 patients died and 2,099 were alive. Patients who died were significantly (P less than .001) older (50 vs. 38 years), had a longer duration of diabetes (33 vs. 22 years), higher systolic blood pressure (146 vs. 134 mm Hg), lower high-density lipoprotein cholesterol (1.38 vs. 1.44 mmol/L), and higher triglycerides (1.25 vs. 0.96 mmol/L). They were also more sedentary, with baseline LTPAs of 8.6 versus 17.2 MET/h (P less than .001). These factors were taken into account while analyzing the data in multiple ways for static and dynamic risk factors.

“These are great data, and this is one of the best clinical studies at the meeting,” observed Viktor Jörgens, MD, former executive director of the EASD and of the European Foundation for the Study of Diabetes, during the post-presentation discussion.

Dr. Jörgens suggested, however, that there was perhaps one important caveat before doctors around the globe started encouraging their patients to exercise more: the level of patient education around the risk for severe hypoglycemia with increasing exercise and routine availability of blood glucose monitoring.

“The problem with severe exercise in type 1 is severe hypoglycemia, and I know Finland is one of the leading countries for patient education and intensified insulin therapy,” Dr. Jörgens cautioned. “Therefore I assume that most of your patients were well educated on blood glucose monitoring, and knew everything about exercise and reducing the dosage [of insulin therapy].” Not all countries may have such high levels of patient education of monitoring, he suggested.

Dr. Tikkanen-Dolenc responded that “of course patient education is needed, such as on continuous glucose monitoring, and there is a risk, but when we look to current recommendations, we still do recommend exercise, even in type 1 diabetes, and it appears to be safe, but that’s a good point and that’s something we need to note.”

Neither Dr. Tikkanen-Dolenc or Dr. Jörgens had anything to disclose.

cenews@frontlinemedcom.com

Exercise reduces T1DM mortality risk