Physical activity in normal and impaired glucose tolerance and Type 2 diabetes mellitus Effects of walking and Nordic walking on health-related quality of life, cardiovascular risk factors and mitochondrial gene expression in overweight individuals

Sammanfattning: Background and aim: Type 2 diabetes mellitus (T2DM) is a disease associated with the risk of severe cardiovascular complications. Genetic predisposition, a sedentary lifestyle and overweight may increase the risk of developing T2DM. The aim was to study the effects of physical activity on risk factors of cardiovascular disease, health-related quality of life, and on the gene expression of enzymes involved in glucose and lipid metabolism, in overweight people with T2DM, impaired or normal glucose tolerance. Methods: Two different exercise intervention studies were conducted, both for a fourmonth period. Study 1, presented in paper I, included 52 T2DM patients, 26 controls, 26 in an intervention group. The intervention was to increase physical activity by brisk walking, 45 minutes three times per week. At baseline and after four months we assessed systolic (SBP) and diastolic (DBP) blood pressure, body mass index (BMI), glucose and lipid metabolic parameters, self-reported physical activity and physical fitness. Study 2 (papers II, III and IV) included 212 overweight individuals. The intervention was a weekly physical activity increase by 5 hours of walking with walking poles (Nordic walking). The participants were classified by an oral glucose tolerance test (OGTT) with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM), and randomized into a control group (n=125), or an exercise intervention group (n=87). Health-related quality of life (HRQoL) was recorded by questionnaire (paper II), and anthropometric and clinical data (papers II & III) were assessed at the time of inclusion and after four months. From 79 NGT and 33 T2DM male exercise participants a 20–100 mg biopsy was taken from the quadriceps muscle of the thigh, for the assessment of messenger RNA (mRNA) expression of mitochondrial genes, coding for enzymes involved in glucose and fatty acid metabolism (paper IV). Results: In study 1 there were no significant improvements of anthropometric parameters, physical fitness, blood pressure, glucose or lipid metabolism. The 17 patients in the intervention group who attained ?80% of the intended increment of physical activity significantly improved SBP, DBP, BMI and total plasma cholesterol, compared with the control group. In study 2 (papers II & III) quality of sleep, body weight, BMI and waist circumference were improved for NGT exercise participants, and in the IGT exercise group exercise capacity improved. Among the exercise participants ?80% compliant with the scheduled time of Nordic walking, exercise capacity improved significantly in all three (NGT, IGT and T2DM) exercise groups. Blood pressure, glycaemic control and blood lipids were unaffected. Baseline mRNA expression of 3 mitochondrial genes was increased in the T2DM group (paper IV). In the NGT group the expression of the enzyme PDK4 was increased after the exercise period, but not in the T2DM group. Conclusions: The exercise participants ?80% compliant with the exercise goals in paper I improved SBP, DBP and BMI. The exercise goal of Nordic walking, 5 hours per week, led to improved quality of sleep, body weight, BMI and waist circumference in the NGT group, and exercise capacity improved in the IGT group. The elevated baseline PDK4 expression and the unaltered post-exercise expression in the T2DM cohort may reflect an impaired utilization of glucose and lipid fuels inherent in T2DM, and a dysfunction of the appropriate adaptive responses to exercise in skeletal muscle associated with insulin resistance.