Glycaemic control influences heart rate responses to cardio-pulmonary exercise testing in type 1 diabetes

Othmar Moser1, Olivia McCarthy1, Rachel Deere1, Max L Eckstein1, Steve C Bain1, Hanne L Haahr2, Eric Zijlstra3, Tim Heise3, Richard M Bracken1

1Diabetes Research Group, Swansea University, Swansea, UK
2Novo Nordisk A/S, Søborg, Denmark
3Profil, Neuss, Germany

Background
In most healthy people, heart rate deviates from a sub-maximal linear increase during later stages of cardio-pulmonary exercise (CPX) testing. This myocardial response is thought to reflect a change in left ventricular ejection fraction (LVEF) and allows for identification of a heart rate turn point (HRTP) beyond which alters myocardial dynamics. In patients with type 1 diabetes both diastolic volume and LVEF fail to adequately increase during aerobic exercise compared with healthy individuals. However, it is not known if the heart rate change in relation to exercise intensity is altered dependent on the glycaemic control in individuals with type 1 diabetes. 

Aim
This study investigated heart rate dynamics during CPX testing and explored relationships to glycaemic state in a group of type 1 diabetes patients. 

Method
Following ethical approval and after providing informed consent sixty-four patients with type 1 diabetes (age: 34.7 ± 7.7 years; 13 females; length of diabetes: 17.1 ± 9 years; HbA1c: 7.81 ± 0.95 % (61.9 ± 13.1 mmol/mol) performed a CPX test until maximum volitional exhaustion (female/male; start: 30/40 watts, increase: 30/40 watts every 3 min). Cardio-pulmonary data were recorded using a PowerCube®-Ergo spirometry system (Ganshorn Medizin Electronic GmbH, GER). The deflection of the heart rate to performance curve was calculated by a second-degree polynomial representation between post-warm up and maximum power output. Relationships were examined between heart rate deflection and diabetes markers, anthropometry and exercise physiological markers and linear regression analysis was performed. ROC curves based on the slope of the increase in heart rate (KHR) for groups kHR < 0.20 vs. > 0.20 in relation to HbA1c and unpaired t-tests were performed with P≤0.05.

Results
We found significant relationships between kHR and HbA1c (r = -0.70, P<0.05), heart rate at HRTP (r = 0.47, P<0.05) and percentage of heart rate at HRTP from maximum heart (HRmax) (r = 0.50, P<0.05). Grouping data based on slope severity (kHR < 0.20, n = 26; 41 % of patients vs. kHR > 0.20, n = 38; 59 % of patients) demonstrated significant differences in HbA1c (8.5 ± 0.8 vs. 7.3 ± 0.7 %, P<0.05), heart rate at HRTP (153 ± 3 vs. 162 ± 2 b/min, P<0.05) and percentage of heart rate at HRTP from HRmax (84 ± 1 vs. 87 ± 1 %, P<0.05) despite similar HRmax (182 ± 2 vs. 186 ± 2 b/min, P>0.05). Furthermore, ROC curve analysis resulted in a HbA1c threshold of 7.9 % (81 % sensitivity, 82 % specificity). 

Discussion
Our data demonstrate atypical heart rate dynamics during CPX testing that was related to glycaemic control in a large group of patients with type 1 diabetes. Type 1 diabetes individuals with elevated HbA1c had a faster increase in heart rate beyond the heart rate turn point than those patients in good glycaemic control. Our data suggest efficacy of CPX testing as a useful assessment in determining alterations in myocardial dynamics based on glycaemic control and warrants more detailed imaging studies. Finally, our data suggest caution in applying physical training recommendations based on heart rate in patients with poor glycaemic control. 

1. 	Heise T, Bain SC, Bracken RM, Zijlstra E, Nosek L, Stender-Petersen K, Rabol R, Rowe E, Haahr HL. Similar risk of exercise-related hypoglycaemia for insulin degludec to that for insulin glargine in patients with type 1 diabetes: a randomized cross-over trial. Diabetes. Obes. Metab. 2016;18(2):196–199.
2. 	Pokan R, Hofmann P, Von Duvillard SP, Beaufort F, Schumacher M, Fruhwald FM, Zweiker R, Eber B, Gasser R, Brandt D, Smekal G, Klein W, Schmid P. Left ventricular function in response to the transition from aerobic to anaerobic metabolism. Med. Sci. Sports Exerc. 1997;29(8):1040–7.
3. 	Galassetti P, Riddell MC. Exercise and type 1 diabetes (T1DM). Compr. Physiol. 2013;3(3):1309–1336.