Diabetes, cardiovascular co-morbidity and environmental temperature: a randomized experimental study (DiabColdHeat)
Purpose: Both high and low environmental temperatures are associated worldwide with higher morbidity and mortality and an estimated 8% of the mortality is estimated to relate to non-optimum temperatures (1). The majority of the adverse health effects occur at to low, and not high temperatures, and already with a modest change in temperature. Persons with type 2 diabetes can be sensitive to the effect of temperature due to their altered neural, metabolic and circulatory functions (2). Our recent population study showed that those with type 2 diabetes reported more cardiac symptoms (arrhythmias, chest pain) during the winter compared with healthy individuals. Furthermore, reporting of cold-related symptoms increased with worsening glycaemia (3). The pathophysiological responses of type 2 diabetes in a cold and hot environment are not known.
Objectives: The aim of the study is to examine how advanced type 2 diabetes (disease progression >10 years) alone, an in conjunction with coronary artery diseases and hypertension affect neural, cardiovascular and metabolic responses in a cold and hot environment.
Hypotheses: Type 2 diabetes is associated with altered neural regulation, weakened cardiovascular function, structural changes in blood vessels, altered blood constitution and metabolic disturbances. These affect thermoregulation and result in increased susceptibility to cold (lesser heat production, increased heat loss) and heat (lesser sweating and heat loss). In addition, type 2 diabetes together with coronary artery disease (CAD) and hypertension (HTN) further weaken cold and heat tolerance due to e.g. changes in the autonomic nervous system, function of superficial blood vessels, impaired endothelial function and altered structure of blood vessels, weakened cardiac function and increase in blood coagulation potential.
Implementation: The patients are exposed under controlled conditions in a random order to both cold (+10°C) and heat (+44°C) while resting and lightly clothed for 90 min at a time. The exposure itself is preceded by baseline measurements of the parameters of interest, and followed by repeating the same measurements after the exposure. The selected exposures are estimated to cause an increase in heat production in cold and initiation of sweating in the heat and are executed at two-week intervals. The research is initiated by pilot measurements (winter 2018), which enables to further define patient selection criteria, as well as optimize the employed cold and heat exposure in the actual broader research entity. The first phase research includes patients with type 2 diabetes and matched controls.
The main parameters of interest of the research are blood pressure (central, peripheral, finger beat-to-beat) and ECG (12-channal, morphology of ECG, arrhythmias, hear rate variability). Secondary parameters of interest: endothelial function (FMD-measurements), skin blood flow, perspiration (heat), oxygen consumption (cold, heat), body and skin temperaturue, blood inflammation factors (CRP, TNFalpha, IL-6, ET-1), stress factors (NA, A), coagulation factors (FVII,vWF, fibrinogen, D-Dimer), lipids (cholesterol), glycemia (HbA1c).
Research results and their applicability: The topic of the research is very relavant due to the worldwide epidemic of type 2 diabetes. Simultaneously, the comorbid conditions associated with diabetes become more common and are related to a higher occurrence of cardiac events. The research information is useful for all individuals with type 2 diabetes in their protection and self-management of the disease, and enabling to maintain functional ability in a cold or hot environment. The research knowledge can be utilized when developing weather warning systems for the identification of susceptible populations. Health care personnel may utilize the research information while advising their patients and for proper care. An increased awareness of the health effects of both low and high temperatures improve the functional ability of individuals and reduced help reducing morbidity and mortality from weather conditions.
Ethical aspects: The controlled study has been apporved by the ethical committee of the Northern Ostrobothnia Hospital District (EETTMK: 199/2016).
Schedule: The project started in 2018 and where pilot measurements will first be conducted. The duration of the broader research is estimated to be three years.
Funding: Yrjö Jahnsson Foundation and Juho Vainio Foundation. Funding has been, and is applied for, the broader research program.
- Gasparrini A, Guo Y, Hashizume M, Lavigne E, Zanobetti A, Schwartz J, Tobias A, Tong S, Rocklöv J, Forsberg B, Leone M, De Sario M, Bell ML, Guo YL, Wu CF, Kan H, Yi SM, de Sousa Zanotti Stagliorio Coelho M, Saldiva PH, Honda Y, Kim H, Armstrong B.Mortality risk attributable to high and low ambient temperature: a multicountry observational study.Lancet. 2015 Jul 25;386(9991):369-75. doi: 10.1016/S0140-6736(14)62114-0.
- Kenny GP, Sigal RJ, McGinn R. Body temperature regulation in diabetes.Temperature (Austin). 2016 Jan 4;3(1):119-45. doi: 10.1080/23328940.2015.1131506.
- Ikäheimo TM, Jokelainen J, Hassi J, Hiltunen L, Keinänen-Kiukaanniemi S, Laatikainen T, Jousilahti P, Peltonen M, Moilanen L, Saltevo J, Näyhä S. Diabetes and impaired glucose metabolism is associated with more cold-related cardiorespiratory symptoms. Diabetes Res Clin Pract. 2017 Jul;129:116-125. doi: 10.1016/j.diabres.2017.04.022.
CERH project website: https://www.oulu.fi/cerh/diabcoldheat_en
Project coordinatorUniversity of Oulu
- Ikäheimo TM, Jokelainen J, Hassi J, Hiltunen L, Keinänen-Kiukaanniemi S, Laatikainen T, Jousilahti P, Peltonen M, Moilanen L, Saltevo J, Näyhä S.Diabetes and impaired glucose metabolism is associated with more cold-related cardiorespiratory symptoms. Diabetes Res Clin Pract. 2017 Jul;129:116-125. doi: 10.1016/j.diabres.2017.04.022. Epub 2017 May 4. https://www.sciencedirect.com/science/article/pii/S0168822717307015?via%3Dihub
- Ikäheimo TM, Jokelainen J, Hassi J, Hiltunen L, Keinänen-Kiukaanniemi S, Laatikainen T, Jousilahti P, Peltonen M, Moilanen L, Saltevo J, Näyhä S. Diabetesta ja sen esiasteita sairastavat oireilevat kylmässä ympäristössä. Best Practice October 2018. https://bestprac.fi/2018/08/31/diabetesta-ja-sen-esiasteita-sairastavat-oireilevat-kylmassa-ymparistossa/
CERH/University of Oulu: Docent Tiina Ikäheimo, Professor Jouni Jaakkola, Doctoral student MHSc. Rasmus Valtonen, Project secretary Riitta Aittamaa
Oulu University Hospital, Research team of cardiovascular diseases: Professor Heikki Huikuri, Docent Juha Perkiömäki, Docent Antti Kiviniemi
Oulu University Hospital, Internal medicine/endocrinology: Docent Tapani Ebeling
City of Oulu/Diabetes polyclinic: Docent Liisa Hiltunen
Finnish Red Cross/Blood Services: MD, Ph.D. Leena Hiltunen
University of Texas Southwestern Medical Center: Professor Craig Crandall
University of Maastricht: Professor Wouter van Marken Liechtenbelt
- Center for Environmental and Respiratory Health Research (CERH)