SIT LESS 2: Effect of Sitting Less on Glucose Regulation in People With Diabetes Mellitus Type 2 (SIT LESS 2)

Introduction: Changes in lifestyle are responsible for an important part of the type 2 diabetes epidemic of the last decennia. Current guidelines for physical activity focus mainly on high energy expenditure advising 30 minutes per day moderate to vigorous physical activity (most often physical exercise). Recent studies suggest that sitting has negative metabolic effects independent of the time spent exercising (Duvivier et al. PLOS ONE 2013). Low intensity physical activity (LIPA) -such as walking and standing- has been suggested to be an alternative to decrease the hyperglycaemic effect of sitting. Compared to exercise, LIPA might be a more feasible strategy. But, it remains to be determined whether reducing sitting time by replacing it by LIPA, results in lower 24 hour blood glucose levels and less blood glucose fluctuations (glycaemic variability) in type 2 diabetes patients and whether these effects are independent of the increase in energy expenditure Methods: The study population will involve 19 people with type 2 diabetes (BMI: 25-35 kg/m2) who perform no, or only little, exercise and who are treated with diet only or with oral blood glucose lowering medication. They will perform three regimes of each four days: 1) a sitting regime, 2) an exercise regime and a 3) sit less regime. Daily energy expenditure of the exercise regime will be identical to that of the sit less regime. Sitting, walking and standing will be objectively measured by a 24 hour physical activity monitor. The energy spent during exercise will be standardised and quantified by using a bicycle ergometer; energy intake will be standardised as well. During each regime blood glucose will be measured with a 24 hour continuous glucose sensor.

The subjects will follow the sitting regime during four days. Each day: 14 hours sitting, 1 hour walking and 1 hour standing for daily care and 8 hours sleeping or lying.

Subjects will follow the sit less regime during four days. Each day will consist of 3 hours walking, 4 hours standing, 9 hours sitting and 8 hours sleeping or lying. The additional 2 hours of walking and 3 hours of standing, compared to the sitting regime, will be done in a minimum of four bouts with a time interval of > 1 hour. The subjects will be instructed to walk on a slow pace. i.e. 2-3 km/h, which is comparable to walking during shopping, walking to the office etc.

Subjects will follow the exercise regime during four days. Each day will consist of 13 hours and 15 minutes sitting, ± 45 minutes supervised cycling on an ergometer, 1 hour walking and 1 hour standing for daily care and 8 hours sleeping or lying.

Inclusion Criteria: Signed informed consent Men and women: 40-75 years old Diabetes mellitus type 2, developed after the age of 40 years old Treatment with diet or oral blood glucose lowering medication (metformin and/or SU-derivatives and/or DPP-IV inhibitors) HbA1c: < 10% BMI: 25.0 - 35.0 kg/m2 Maximum 2.5 hours of MVPA per week (during last 3 months) Internet availability on a daily basis Exclusion Criteria: Pregnancy or intention of becoming pregnant Alcohol use: > 2 units per day (during the last 3 months) Experimental drug use (during the last 3 months) Use of insulin, corticosteroids, vitamin K antagonists and immunosuppressive drugs in the last 3 months Triglyceride level > 10.0 mmol/L Fasting plasma glucose level > 10 mmol/L Heart failure NYHA 3 or higher Angina pectoris or signs of cardiac ischemia during exercise testing COPD Gold 3 or higher Glomerular filtration rate (GFR) < 30 ml/min Diagnosis of active cancer (not cancer in the past that is cured) Diabetes mellitus type 1 Intermittent claudication with a walking distance < 500 meter Not able to cycle for ± 45 minutes, as judged from the incremental exhaustive exercise bicycle-ergometer test at Visit 1 Based on historical information not able to walk for 3 hours per day and stand for 4 hours per day Mental or physical disability which makes physical activity not possible Participation in a clinical trial with medication use (in the last 3 months) Severe loss of vision Active foot ulcer or venous leg ulcer

Duvivier BM, Schaper NC, Bremers MA, van Crombrugge G, Menheere PP, Kars M, Savelberg HH. Minimal intensity physical activity (standing and walking) of longer duration improves insulin action and plasma lipids more than shorter periods of moderate to vigorous exercise (cycling) in sedentary subjects when energy expenditure is comparable. PLoS One. 2013;8(2):e55542. doi: 10.1371/journal.pone.0055542. Epub 2013 Feb 13. Erratum In: PLoS One. 2014;9(8):e105135.

Duvivier BM, Schaper NC, Hesselink MK, van Kan L, Stienen N, Winkens B, Koster A, Savelberg HH. Breaking sitting with light activities vs structured exercise: a randomised crossover study demonstrating benefits for glycaemic control and insulin sensitivity in type 2 diabetes. Diabetologia. 2017 Mar;60(3):490-498. doi: 10.1007/s00125-016-4161-7. Epub 2016 Nov 30.