Winter-Swimming and Brown Adipose Tissue Activity in Middel-aged Obese Subjects (WinterBAT). (WinterBAT)

The Impact of Winter Swimming on Brown Adipose Tissue Recruitment and Metabolic Health in Middel-aged Obese Pre-diabetic Subjects.

This study investigates repetitive cold-water exposure on brown fat activity assessed by infrared thermography imagine. Furthermore we will assess glucose control upon winter-swimming. Obese prediabetic men and women will be randomized to winter-swimming or control conditions for 4 months.

Brown fat (BAT) is an energy-consuming tissue. Long-term activation of BAT in adults increases clearance of blood glucose and non-esterified fatty acids (NEFA), insulin sensitivity and metabolic rate. Moreover, adipokines released from BAT, known as batokines, represent a promising but currently unexplored area in terms of metabolic regulation. Cooling activates BAT; however, current cooling protocols fail to activate BAT in a large part of the population. Whether this failure in activation is related to biology, inefficient detection or cooling protocols is unknown. With our initial acute cooling study (protocol number: H-16038581), these protocols have successfully been optimized whereupon novel batokines will be identified. Having established a methodology for assessing BAT activity and batokine profiles, a longer-term cooling intervention (winter swimming) will be performed to examine the effect of repetitive cold-water exposure on BAT activity. Obese pre-diabetic subjects will be included in a 4-month supervised winter swimming (WS) intervention. It is hypothesized, that repetitive cold-water exposure constituted by WS, alters increase BAT activation and volume, followed by improved glycemic control in obese pre-diabetic subjects. Method The study is a randomized controlled, parallel-group intervention study. The investigator will recruit 30 obese pre-diabetic non-winter-swimmers to participate in a WS intervention group (n=15) or control group (n=15) with no WS activities. Subjects will either be randomized to the WS group, who will winter-swim 4 months, 2-3 times/week including sauna-visits if desired, or control conditions with no WS during the 4 months (October to May). Main aims To assess whether WS will have an immediate effect on BAT recruitment or function. To assess whether WS will have an effect on glycemic control.

Adipose Tissue, Brown, Brown Adipose Tissue, Uncoupling Protein 1, Cold Exposure, Obesity, Type 2 Diabetes Mellitus, Winter Swimming

Difference in brown adipose tissue (BAT) activity after cooling between Winter Swimmers (WS) and No-Winter Swimmers (NWS).

BAT activity is measured by skin temperature in the supraclavicular BAT depot using infrared thermography imaging. Difference between peak temperature change (peak temperature minus baseline temperature) during 3 hours of cooling is calculated.

Glycemic control is measured by a 2 hour oral glucose tolerance test. Difference in the 2 hour sample will be calculated before and after the 4 months winter swimming intervention.

Difference in glucose control after a 2 hour oral glucose tolerance test before versus after 4 months of winter swimming.

Inclusion Criteria: Waist circumference above 80 cm for women and 94 cm for men. BMI > 25 but <40 kg/m2 Age > 40 years. Low to moderate physical activity level (no physical activity or on average 30 minutes of moderate physical activity per day and not more than 3 hours of training pr. Week) Subjects will be included in either one of these cases after the screening: Fasting plasma glucose above 5.6 millimol per liter (mmoL/L). HbA1C >39 millimol per mol (mmol/mol). 2 hour plasma glucose after a 75 g. oral glucose tolerance test (OGTT) above 7.8 mmol/L. Exclusion Criteria: Winter swimmer Any history of Cancer, Clinically significant liver, kidney, heart, inflammatory or lung-disease. Pregnancy Taking medication (not for hay fever), including glucose-lowering treatment. HbA1c >55 mmol/mol and/or 2-h plasma glucose in the 75-g OGTT > 15 mmol/L, fasting plasma glucose above 6.9. Iron deficiency Increased International Normalised Ratio for coagulation (INR). Femoral hernia, vene prostheses (pants prosthesis), thrombs in v. Femoralis. Abnormal ultrasound echocardiography of the heart found at the health-examination day. Contraindications to cold exposure including severe Raynauds disease. History of alcohol abuse or use of more than 14 units pr. Week. History of drug abuse, including marihuana. Smoking including occasional smoking. Pacemaker or other electronics implanted in the body. Claustrophobia, communication problems, including understanding the experimental protocol. History of contrast allergy.

Hanssen MJ, Hoeks J, Brans B, van der Lans AA, Schaart G, van den Driessche JJ, Jorgensen JA, Boekschoten MV, Hesselink MK, Havekes B, Kersten S, Mottaghy FM, van Marken Lichtenbelt WD, Schrauwen P. Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Nat Med. 2015 Aug;21(8):863-5. doi: 10.1038/nm.3891. Epub 2015 Jul 6.

Hanssen MJ, van der Lans AA, Brans B, Hoeks J, Jardon KM, Schaart G, Mottaghy FM, Schrauwen P, van Marken Lichtenbelt WD. Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans. Diabetes. 2016 May;65(5):1179-89. doi: 10.2337/db15-1372. Epub 2015 Dec 30.

van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009 Apr 9;360(15):1500-8. doi: 10.1056/NEJMoa0808718. Erratum In: N Engl J Med. 2009 Apr 30;360(18):1917.

Lee P, Smith S, Linderman J, Courville AB, Brychta RJ, Dieckmann W, Werner CD, Chen KY, Celi FS. Temperature-acclimated brown adipose tissue modulates insulin sensitivity in humans. Diabetes. 2014 Nov;63(11):3686-98. doi: 10.2337/db14-0513. Epub 2014 Jun 22.

Gibas-Dorna M, Checinska Z, Korek E, Kupsz J, Sowinska A, Krauss H. Cold Water Swimming Beneficially Modulates Insulin Sensitivity in Middle-Aged Individuals. J Aging Phys Act. 2016 Oct;24(4):547-554. doi: 10.1123/japa.2015-0222. Epub 2016 Aug 24.