Kyung Ah Han

Effects of Exercise on sRAGE Levels and Cardiometabolic Risk Factors in Patients with Type 2 Diabetes: A Randomized Controlled Trial

CONTEXT Low levels of soluble receptor for advanced glycation end-products (sRAGE) have been linked to systemic inflammation and vascular complications in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE We examined the effects of exercise on sRAGE and its association with diverse cardiometabolic risk factors and indicators of atherosclerosis in patients with T2DM. DESIGN, SETTING, AND PARTICIPANTS Seventy-five patients with T2DM were randomized into a control group and an aerobic exercise group (60 min at moderate intensity, five times/wk for 12 wk). MAIN OUTCOME MEASURES We evaluated sRAGE, energy expenditure, dietary energy intake, cardiorespiratory fitness, inflammatory markers, visceral fat area, pulse-wave velocity, and flow-mediated dilatation. RESULTS Baseline sRAGE concentrations were independently associated with age, glycated hemoglobin, glucose, triglyceride, and high-density lipoprotein cholesterol levels (R2=0.244). After 12 wk of exercise training, the exercise group showed significantly decreased body weight, waist circumference, blood pressure, glycated hemoglobin, apolipoprotein B, and free fatty acid levels. Concurrently, cardiorespiratory fitness assessed by oxygen uptake at anaerobic threshold was improved, and body fat percentage and visceral fat area were significantly decreased in the exercise group, although pulse-wave velocity and flow-mediated dilatation were not changed. Furthermore, sRAGE levels were increased and high-sensitivity C-reactive protein levels were decreased in the exercise group but not in the control group. Percent change of sRAGE level was negatively correlated with that of high-sensitivity C-reactive protein during the study period (r=-0.27; P=0.019). CONCLUSIONS Aerobic exercise increases sRAGE levels along with improvement of various cardiometabolic risk factors in patients with T2DM.

The effects of resistance training on muscle and body fat mass and muscle strength in type 2 diabetic women.

Background Our goal was to investigate the effects of low intensity resistance training on body fat, muscle mass and strength, cardiovascular fitness, and insulin sensitivity in type 2 diabetes. Methods Twenty-eight overweight women with type 2 diabetes were randomly assigned to a resistance training group (RG, n = 13) or a control group (CG, n = 15). RG performed resistance training using elastic bands, of which strength was equal to 40 to 50% of one repetition maximum (1RM), for three days per week. Each exercise consisted of three sets for 60 minutes. We assessed abdominal fat using computed tomography, muscle mass using dual-energy X-ray absorptiometry, and muscle strength using Keisers chest and leg press. Insulin sensitivity was measured using the insulin tolerance test, and aerobic capacity was expressed as oxygen uptake at the anaerobic threshold (AT-VO2) before and after the 12-week exercise program. Results The age of participants was 56.4 ± 7.1 years, duration of diabetes was 5.9 ± 5.5 years, and BMI was 27.4 ± 2.5 kg/m2, without significant differences between two groups. During intervention, a greater increase in muscle mass and greater decreases in both total fat mass and abdominal fat were observed in RG compared to those of CG (P = 0.015, P = 0.011, P = 0.010, respectively). Increase in 1RM of upper and lower extremities was observed in the RG (P = 0.004, P = 0.040, respectively), without changes in AT-VO2 and insulin resistance in either group. Conclusion In conclusion, the low intensity resistance training was effective in increasing muscle mass and strength and reducing total fat mass without change of insulin sensitivity in type 2 diabetic patients.

The effects of caloric restriction on fetuin-A and cardiovascular risk factors in rats and humans: a randomized controlled trial.

The liver‐secreted protein fetuin‐A is associated with insulin resistance, metabolic syndrome, type 2 diabetes and atherosclerosis. We examined the effect of caloric restriction (CR) on fetuin‐A levels and concomitant changes in hepatic steatosis and cardiovascular risk factors in rats and humans.

Effects of Pinitol on Glycemic Control, Insulin Resistance and Adipocytokine Levels in Patients with Type 2 Diabetes Mellitus

Background: Pinitol is thought to mediate insulin action and improve insulin resistance. We evaluated the effects of pinitol on glycemic control, insulin resistance and adipocytokine levels in type 2 diabetic patients. Material and Method: A total of 66 patients with type 2 diabetes who had been taking oral hypoglycemic agents for at least 3 months were enrolled and randomized to receive pinitol (n = 33) or matching placebo (n = 33). All subjects took 1,200 mg pinitol or placebo and maintained their current oral hypoglycemic agents throughout the study. Results: Mean HbA1c, fasting plasma glucose, and HOMA-IR were significantly lowered more in patients taking pinitol than in those given a placebo. Patients who had an HbA1c over 8.0% showed a greater reduction (p < 0.01) than those who had an HbA1c below 8.0% (p =0.16). In addition, in the group of patients with a HOMA-IR over 2.5, there was a significant decrease in HbA1c compared to that in the group of patients with a HOMA-IR below 2.5. There were no differences in the changes in adiponectin, FFA and CRP between the two groups. Conclusions: Pinitol can mediate insulin action to improve glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus, especially in patients with insulin resistance.

Effects of Aerobic Exercise on Abdominal Fat, Thigh Muscle Mass and Muscle Strength in Type 2 Diabetic Subject

Background Aerobic exercise can effectively reduce visceral fat. However, few studies have examined the effect of daily physical activity on obesity and cardiopulmonary function in the subjects with diabetes. We examined the effect of moderate intensity of walking in obese diabetes patients by monitoring of daily activity and measuring the change in abdominal fat area, muscle are and maximal muscle strength. Methods We randomly assigned 27 obese women with type 2 diabetes to an aerobic exercise group (AG, n = 13) and control group (CG, n = 14). The AG performed moderate intensity walking for 60 minutes per exercise, 5 times per week, and for 12 weeks. The activity energy expenditure was monitored by a multi-record accelerometer. The CG maintained routine daily activities. At the time of the initiation of the study and after 12 weeks of exercise, the aerobic exercise capacity was assessed using oxygen consumption rate at anaerobic threshold (VO2-AT). The abdominal fat area and the quadriceps muscle area were measured by computed tomography, and the maximum muscle strength of the upper and lower limbs was measured by a chest press and a leg press, respectively. Results The mean age of the study subjects was 56.6 ± 8.0 years, the mean duration of diabetes was 6.3 ± 6.0 years, and the body weight index (BMI) was 27.3 ± 2.7 kg/m2. The BMI of the AG was significantly decreased (P = 0.003). In the AG, the visceral fat area and subcutaneous fat area were also significantly decreased (P = 0.018 and P < 0.001, respectively) but not in CG. VO2-AT of the AG was significantly improved, while that of the CG did not change (P = 0.009 and P = 0.115, respectively). The quadriceps muscle mass and the maximal muscle strength of the AG did not change, however, the CG showed a significant decrease. Duration of moderate intensity exercise was correlated with the decrease in total abdominal fat area (r = -0.484; P = 0.011) and that of high intensity exercise was correlated with improvement of cardiopulmonary function (r = 0.414; P = 0.032). Conclusion Daily moderate intensity aerobic exercise is effective at reducing abdominal fat mass, while high intensity exercise improves cardiopulmonary function.

Valsartan Increases Circulating Adiponectin Levels without Changing HOMA-IR in Patients with Type 2 Diabetes Mellitus and Hypertension

Evaluating increasing circulating adiponectin levels is becoming an important strategy in the prevention of diabetes mellitus and cardiovascular events. This study was designed to investigate the effect of the angiotensin II receptor blocker valsartan on blood adiponectin levels and insulin sensitivity in patients with type 2 diabetes and mild-to-moderate hypertension. A total of 91 Korean patients were treated with 80 mg/day valsartan for 4 weeks followed by 160 mg/day for a further 8 weeks. Blood pressure, adiponectin levels and metabolic parameters were measured before and after treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as an insulin sensitivity index. Valsartan significantly decreased mean blood pressure and increased circulating adiponectin levels. There were no differences in metabolic parameters, including HOMA-IR, glycosylated haemoglobin and lipid levels before and after treatment. These results indicated that valsartan increases circulating adiponectin levels, but does not change insulin sensitivity in patients with type 2 diabetes and mild-to-moderate hypertension.

Effects of Aerobic Exercise Intensity on Abdominal and Thigh Adipose Tissue and Skeletal Muscle Attenuation in Overweight Women with Type 2 Diabetes Mellitus

Background We investigated the effects of exercise intensity on abdominal and mid-thigh adipose tissue, attenuation of skeletal muscle, and insulin sensitivity in overweight women with type 2 diabetes mellitus (T2DM). Methods Twenty-eight patients were randomly assigned to control (CG, n=12), moderate intensity exercise (MEG, n=8), or vigorous intensity exercise (VEG, n=8) group. Subjects in both exercise groups completed a 12-week exercise program (MEG, 3.6 to 5.2 METs; VEG, ≥5.2 METs) that was monitored by accelerometers. We assessed body mass index (BMI), total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), mid-thigh intramuscular adipose tissue (TIMAT), total skeletal muscle (TTM), low density skeletal muscle (TLDM), and normal density skeletal muscle (TNDM) using computed tomography, and measured insulin sensitivity with an insulin tolerance test (KITT), before and after the intervention. Results At baseline, the mean age was 53.8±7.9 years, duration of diabetes was 3.8±2.3 years, and BMI was 26.6±2.6 kg/m2. After 12 weeks, the percent change (%C) in BMI, TIMAT, and TLDM were not different among three groups. However, %C in TFA and VFA were significantly reduced in MEG compared to CG (P=0.026 and P=0.008, respectively). %C SFA was significantly reduced in VEG compared to CG (P=0.038) and %C TTM, TNDM, and KITT were significantly increased in VEG compared to the CG (P=0.044, P=0.007, and P=0.016, respectively). Conclusion Although there was no difference in the change in BMI among groups, TFA and VFA were more reduced in MEG, and only VEG increased TTM, TNDM, and insulin sensitivity compared to CG.

Relation of Absolute or Relative Adiposity to Insulin Resistance, Retinol Binding Protein-4, Leptin, and Adiponectin in Type 2 Diabetes

Background Central fat mass (CFM) correlates with insulin resistance and increases the risk of type 2 diabetes and cardiovascular complications; however, peripheral fat mass (PFM) is associated with insulin sensitivity. The aim of this study was to investigate the relation of absolute and relative regional adiposity to insulin resistance index and adipokines in type 2 diabetes. Methods Total of 83 overweighted-Korean women with type 2 diabetes were enrolled, and rate constants for plasma glucose disappearance (KITT) and serum adipokines, such as retinol binding protein-4 (RBP4), leptin, and adiponectin, were measured. Using dual X-ray absorptiometry, trunk fat mass (in kilograms) was defined as CFM, sum of fat mass on the lower extremities (in kilograms) as PFM, and sum of CFM and PFM as total fat mass (TFM). PFM/TFM ratio, CFM/TFM ratio, and PFM/CFM ratio were defined as relative adiposity. Results Median age was 55.9 years, mean body mass index 27.2 kg/m2, and mean HbA1c level 7.12±0.84%. KITT was positively associated with PMF/TFM ratio, PMF/CFM ratio, and negatively with CFM/TFM ratio, but was not associated with TFM, PFM, or CFM. RBP4 levels also had a significant relationship with PMF/TFM ratio and PMF/CFM ratio. Adiponectin, leptin, and apolipoprotein A levels were related to absolute adiposity, while only adiponectin to relative adiposity. In correlation analysis, KITT in type 2 diabetes was positively related with HbA1c, fasting glucose, RBP4, and free fatty acid. Conclusion These results suggest that increased relative amount of peripheral fat mass may aggravate insulin resistance in type 2 diabetes.

The Effect of an Angiotensin Receptor Blocker on Arterial Stiffness in Type 2 Diabetes Mellitus Patients with Hypertension

Background Hypertension and type 2 diabetes mellitus are major risk factors for cardiovascular disease. This study analyzed the changes in central aortic waveforms and pulse wave velocity as well as related parameters after treatment with valsartan, an angiotensin II type 1 receptor blocker, in patients with type 2 diabetes and hypertension. Methods We used pulse wave analysis to measure central aortic waveform in a total of 98 subjects. In 47 of these patients, pulse wave velocity measurements were obtained before and after 12 weeks of treatment with valsartan. Results In the central aortic waveform analysis, the aortic pulse pressure and augmentation index were significantly decreased after valsartan treatment, as was the aortic pulse wave velocity. Factors contributing to the improvement in pulse wave velocity were the fasting blood glucose and haemoglobin A1c levels. Conclusion Short-term treatment with valsartan improves arterial stiffness in patients with type 2 diabetes and hypertension, and the glucose status at baseline was associated with this effect.

Cardiovascular Risk Assessment with Vascular Function, Carotid Atherosclerosis and the UKPDS Risk Engine in Korean Patients with Newly Diagnosed Type 2 Diabetes

Background Patients with type 2 diabetes have an increased risk of cardiovascular disease. Few studies have evaluated the cardiovascular disease (CVD) risk simultaneously using the United Kingdom Prospective Diabetes Study (UKPDS) risk engine and non-invasive vascular tests in patients with newly diagnosed type 2 diabetes. Methods Participants (n=380; aged 20 to 81 years) with newly diagnosed type 2 diabetes were free of clinical evidence of CVD. The 10-year coronary heart disease (CHD) and stroke risks were calculated for each patient using the UKPDS risk engine. Carotid intima media thickness (CIMT), flow mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AI) were measured. The correlations between the UKPDS risk engine and the non-invasive vascular tests were assessed using partial correlation analysis, after adjusting for age, and multiple regression analysis. Results The mean 10-year CHD and 10-year stroke risks were 14.92±11.53% and 4.03±3.95%, respectively. The 10-year CHD risk correlated with CIMT (P<0.001), FMD (P=0.017), and PWV (P=0.35) after adjusting for age. The 10-year stroke risk correlated only with the mean CIMT (P<0.001) after adjusting for age. FMD correlated with age (P<0.01) and systolic blood pressure (P=0.09). CIMT correlated with age (P<0.01), HbA1c (P=0.05), and gender (P<0.01). Conclusion The CVD risk is increased at the onset of type 2 diabetes. CIMT, FMD, and PWV along with the UKPDS risk engine should be considered to evaluate cardiovascular disease risk in patients with newly diagnosed type 2 diabetes.