Neil M. Johannsen

Effects of Aerobic and Resistance Training on Hemoglobin A1c Levels in Patients With Type 2 Diabetes: A Randomized Controlled Trial

CONTEXT Exercise guidelines for individuals with diabetes include both aerobic and resistance training although few studies have directly examined this exercise combination. OBJECTIVE To examine the benefits of aerobic training alone, resistance training alone, and a combination of both on hemoglobin A(1c) (HbA(1c)) in individuals with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS A randomized controlled trial in which 262 sedentary men and women in Louisiana with type 2 diabetes and HbA(1c) levels of 6.5% or higher were enrolled in the 9-month exercise program between April 2007 and August 2009. INTERVENTION Forty-one participants were assigned to the nonexercise control group, 73 to resistance training 3 days a week, 72 to aerobic exercise in which they expended 12 kcal/kg per week; and 76 to combined aerobic and resistance training in which they expended 10 kcal/kg per week and engaged in resistance training twice a week. Main Outcome Change in HbA(1c) level. Secondary outcomes included measures of anthropometry and fitness. RESULTS The study included 63.0% women and 47.3% nonwhite participants who were a mean (SD) age of 55.8 years (8.7 years) with a baseline HbA(1c) level of 7.7% (1.0%). Compared with the control group, the absolute mean change in HbA(1c) in the combination training exercise group was -0.34% (95% confidence interval [CI], -0.64% to -0.03%; P = .03). The mean changes in HbA(1c) were not statistically significant in either the resistance training (-0.16%; 95% CI, -0.46% to 0.15%; P = .32) or the aerobic (-0.24%; 95% CI, -0.55% to 0.07%; P = .14) groups compared with the control group. Only the combination exercise group improved maximum oxygen consumption (mean, 1.0 mL/kg per min; 95% CI, 0.5-1.5, P < .05) compared with the control group. All exercise groups reduced waist circumference from -1.9 to -2.8 cm compared with the control group. The resistance training group lost a mean of -1.4 kg fat mass (95% CI, -2.0 to -0.7 kg; P < .05) and combination training group lost a mean of -1.7 (-2.3 to -1.1 kg; P < .05) compared with the control group. CONCLUSIONS Among patients with type 2 diabetes mellitus, a combination of aerobic and resistance training compared with the nonexercise control group improved HbA(1c) levels. This was not achieved by aerobic or resistance training alone. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00458133.

The Role of Exercise and Physical Activity in Weight Loss and Maintenance

This review explores the role of physical activity (PA) and exercise training (ET) in the prevention of weight gain, initial weight loss, weight maintenance, and the obesity paradox. In particular, we will focus the discussion on the expected initial weight loss from different ET programs, and explore intensity/volume relationships. Based on the present literature, unless the overall volume of aerobic ET is very high, clinically significant weight loss is unlikely to occur. Also, ET also has an important role in weight regain after initial weight loss. Overall, aerobic ET programs consistent with public health recommendations may promote up to modest weight loss (~2 kg), however the weight loss on an individual level is highly heterogeneous. Clinicians should educate their patients on reasonable expectations of weight loss based on their physical activity program and emphasize that numerous health benefits occur from PA programs in the absence of weight loss.

Exercise and the Cardiovascular System: Clinical Science and Cardiovascular Outcomes

Substantial evidence has established the value of high levels of physical activity, exercise training (ET), and overall cardiorespiratory fitness in the prevention and treatment of cardiovascular diseases. This article reviews some basics of exercise physiology and the acute and chronic responses of ET, as well as the effect of physical activity and cardiorespiratory fitness on cardiovascular diseases. This review also surveys data from epidemiological and ET studies in the primary and secondary prevention of cardiovascular diseases, particularly coronary heart disease and heart failure. These data strongly support the routine prescription of ET to all patients and referrals for patients with cardiovascular diseases, especially coronary heart disease and heart failure, to specific cardiac rehabilitation and ET programs.

Metabolic Syndrome and Diabetes, Alone and in Combination, as Predictors of Cardiovascular Disease Mortality Among Men

OBJECTIVE To examine cardiovascular disease (CVD) mortality risk in men with diabetes only, metabolic syndrome only, and concurrent metabolic syndrome and diabetes. RESEARCH DESIGN AND METHODS We examined CVD mortality risk by metabolic syndrome and diabetes status in men from the Aerobics Center Longitudinal Study (ACLS) (mean ± SD age 45.1 ± 10.2 years). Participants were categorized as having neither diabetes nor metabolic syndrome (n = 23,770), metabolic syndrome only (n = 8,780), diabetes only (n = 532), or both (n = 1,097). The duration of follow-up was 14.6 ± 7.0 years with a total of 483,079 person-years of exposure and 1,085 CVD deaths. RESULTS Age-, examination year–, and smoking-adjusted CVD death rates (per 1,000 man-years) in men with neither metabolic syndrome nor diabetes, metabolic syndrome only, diabetes only, and both were 1.9, 3.3, 5.5, and 6.5, respectively. CVD mortality was higher in men with metabolic syndrome only (hazard ratio 1.8 [95% CI 1.5–2.0]), diabetes only (2.9 [2.1–4.0]), and both (3.4 [2.8–4.2]) compared with men with neither. The presence of metabolic syndrome was not associated (1.2 [0.8–1.7]) with higher CVD mortality risk in individuals with diabetes. In contrast, the presence of diabetes substantially increased (2.1 [1.7–2.6]) CVD mortality risk in individuals with metabolic syndrome. CONCLUSIONS The presence of diabetes was associated with a threefold higher CVD mortality risk, and metabolic syndrome status did not modify this risk. Our findings support the fact that physicians should be aggressive in using CVD risk–reducing therapies in all diabetic patients regardless of metabolic syndrome status.

Nine Months of Combined Training Improves Ex Vivo Skeletal Muscle Metabolism in Individuals With Type 2 Diabetes

CONTEXT Type 2 diabetes (T2D) has features of disordered lipid and glucose metabolism, due in part to reduced mitochondrial content. OBJECTIVE Our objective was to investigate effects of different types of exercise on mitochondrial content and substrate oxidation in individuals with T2D (ancillary study of the randomized controlled trial Health Benefits of Aerobic and Resistance Training in Individuals with Type 2 Diabetes, HART-D). INTERVENTION T2D individuals were randomized to aerobic training (AT, n = 12), resistance training (RT, n = 18), combination training (ATRT, n = 12), or nonexercise control (n = 10). Blood draws, peak oxygen consumption tests, dual-energy x-ray absorptiometry scans and muscle biopsies of vastus lateralis were performed before and after 9 months. Ex vivo substrate oxidations ((14)CO2), mitochondrial content, and enzyme activities were measured. Glycated hemoglobin A1c and free fatty acids were also determined. RESULTS Mitochondrial content increased after RT and ATRT. Octanoate oxidation increased after AT and ATRT, whereas palmitate, pyruvate, and acetate oxidations increased in all exercise groups. Exercise-induced responses in mitochondrial DNA were associated with improvements in peak oxygen consumption, β-hydroxyacyl-coenzyme A dehydrogenase activity, and palmitate oxidation. CONCLUSIONS Nine months of AT and RT significantly improved most aspects of skeletal muscle mitochondrial content and substrate oxidation, whereas the combination improved all aspects. These exercise responses were associated with clinical improvements, indicating that long-term training, especially combination, is an effective lifestyle therapy for individuals with T2D by way of improving muscle substrate metabolism.

Exercise Training and Quality of Life in Individuals With Type 2 Diabetes A randomized controlled trial

OBJECTIVE To establish whether exercise improves quality of life (QOL) in individuals with type 2 diabetes and which exercise modalities are involved. RESEARCH DESIGN AND METHODS Health Benefits of Aerobic and Resistance Training in individuals with type 2 Diabetes (HART-D; n = 262) was a 9-month exercise study comparing the effects of aerobic training, resistance training, or a combination of resistance and aerobic training versus a nonexercise control group on hemoglobin A1c (HbA1c) in sedentary individuals with type 2 diabetes. This study is an ancillary analysis that examined changes in QOL after exercise training using the Short Form-36 Health Survey questionnaire compared across treatment groups and with U.S. national norms. RESULTS The ancillary sample (n = 173) had high baseline QOL compared with U.S. national norms. The QOL physical component subscale (PCS) and the general health (GH) subscale were improved by all three exercise training conditions compared with the control group condition (resistance: PCS, P = 0.005; GH, P = 0.003; aerobic: PCS, P = 0.001; GH, P = 0.024; combined: PCS, P = 0.015; GH, P = 0.024). The resistance training group had the most beneficial changes in bodily pain (P = 0.026), whereas physical functioning was most improved in the aerobic and combined condition groups (P = 0.025 and P = 0.03, respectively). The changes in the mental component score did not differ between the control group and any of the exercise groups (all P > 0.05). The combined training condition group had greater gains than the aerobic training condition group in the mental component score (P = 0.004), vitality (P = 0.031), and mental health (P = 0.008) and greater gains in vitality compared with the control group (P = 0.021). CONCLUSIONS Exercise improves QOL in individuals with type 2 diabetes. Combined aerobic/resistance exercise produces greater benefit in some QOL domains.

The effect of exercise training modality on serum brain derived neurotrophic factor levels in individuals with type 2 diabetes.

Introduction Brain derived neurotrophic factor (BDNF) has been implicated in memory, learning, and neurodegenerative diseases. However, the relationship of BDNF with cardiometabolic risk factors is unclear, and the effect of exercise training on BDNF has not been previously explored in individuals with type 2 diabetes. Methods Men and women (N = 150) with type 2 diabetes were randomized to an aerobic exercise (aerobic), resistance exercise (resistance), or a combination of both (combination) for 9 months. Serum BDNF levels were evaluated at baseline and follow-up from archived blood samples. Results Baseline serum BDNF was not associated with fitness, body composition, anthropometry, glucose control, or strength measures (all, p>0.05). Similarly, no significant change in serum BDNF levels was observed following exercise training in the aerobic (−1649.4 pg/ml, CI: −4768.9 to 1470.2), resistance (−2351.2 pg/ml, CI:−5290.7 to 588.3), or combination groups (−827.4 pg/ml, CI: −3533.3 to1878.5) compared to the control group (−2320.0 pg/ml, CI: −5750.8 to 1110.8). However, reductions in waist circumference were directly associated with changes in serum BDNF following training (r = 0.25, p = 0.005). Conclusions Serum BDNF was not associated with fitness, body composition, anthropometry, glucose control, or strength measures at baseline. Likewise, serum BDNF measures were not altered by 9 months of aerobic, resistance, or combination training. However, reductions in waist circumference were associated with decreased serum BDNF levels. Future studies should investigate the relevance of BDNF with measures of cognitive function specifically in individuals with type-2 diabetes.

Effect of Different Doses of Aerobic Exercise on Total White Blood Cell (WBC) and WBC Subfraction Number in Postmenopausal Women: Results from DREW

Background Elevated total white blood cell (WBC) count is associated with an increased risk of coronary heart disease and death. Aerobic exercise is associated with lower total WBC, neutrophil, and monocyte counts. However, no studies have evaluated the effect of the amount of aerobic exercise (dose) on total WBC and WBC subfraction counts. Purpose To examine the effects of 3 different doses of aerobic exercise on changes in total WBC and WBC subfraction counts and independent effects of changes in fitness, adiposity, markers of inflammation (IL-6, TNF-α, C-reactive protein), fasting glucose metabolism, and adiponectin. Methods Data from 390 sedentary, overweight/obese postmenopausal women from the DREW study were used in these analyses. Women were randomized to a non-exercise control group or one of 3 exercise groups: energy expenditure of 4, 8, or 12 kcal kg−1⋅week−1 (KKW) for 6 months at an intensity of 50% VO2peak. Results A dose-dependent decrease in total WBC counts (trend P = 0.002) was observed with a significant decrease in the 12KKW group (−163.1±140.0 cells/µL; mean±95%CI) compared with the control (138.6±144.7 cells/µL). A similar response was seen in the neutrophil subfraction (trend P = 0.001) with a significant decrease in the 12KKW group (−152.6±115.1 cells/µL) compared with both the control and 4KKW groups (96.4±119.0 and 21.9±95.3 cells/µL, respectively) and in the 8KKW group (−102.4±125.0 cells/µL) compared with the control. When divided into high/low baseline WBC categories (median split), a dose-dependent decrease in both total WBCs (P = 0.003) and neutrophils (P<0.001) was observed in women with high baseline WBC counts. The effects of exercise dose on total WBC and neutrophil counts persisted after accounting for significant independent effects of change in waist circumference and IL-6. Conclusion Aerobic exercise training reduces total WBC and neutrophil counts, in a dose-dependent manner, in overweight/obese postmenopausal women and is especially beneficial for those with systemic low grade inflammation. Clinical Trials Identifier: NCT00011193

A transcriptional signature of “exercise resistance” in skeletal muscle of individuals with type 2 diabetes mellitus

AIMS/HYPOTHESIS Exercise benefits most, but not all, individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to determine whether a proportion of individuals with T2DM would fail to demonstrate exercise-induced metabolic improvements. We hypothesized that this lack of response would be related to their skeletal muscle transcriptional profile. METHODS 42 participants with T2DM from the previously reported HART-D study underwent a 9-month supervised exercise intervention. We performed a principal components analysis to distinguish Responders from Non-Responders (n=9 each) based on: decreases in (1) HbA1c, (2) %fat (3) BMI and (4) increase in skeletal muscle mtDNA. mRNA expression patterns in muscle tissue at baseline were assessed by microarray and qRT-PCR analysis in both groups. RESULTS Of 186 genes identified by microarray analysis, 70% were up-regulated in Responders and down-regulated in Non-Responders. Several genes involved in substrate metabolism and mitochondrial biogenesis were significantly different (fold-change>1.5, p<0.05) between the groups at baseline, indicating a blunted oxidative capacity at baseline in Non-Responders. CONCLUSIONS/INTERPRETATIONS These data suggest that a unique baseline expression pattern of genes involved in muscle fuel metabolism may predict an individuals lack of exercise response in metabolic outcomes, thus allowing exercise interventions to be targeted to these individuals and aid in the identification of novel approaches to treat Non-Responders in the future.

Low cardiorespiratory fitness in African Americans: a health disparity risk factor?

Low cardiorespiratory fitness (CRF) is a well-established risk factor for all-cause and cardiovascular disease mortality. African Americans have higher rates of cardiovascular disease compared with their Caucasian counterparts. However, the extent to which lower CRF levels contribute to the excess risk in African Americans has not been fully explored. The purpose of this review is to: (i) explore the literature evaluating the relationship between CRF and mortality specifically in African American populations; and (ii) critically evaluate the studies which have compared CRF between African American and Caucasians in epidemiological studies and clinical trials. We have further discussed several potential mechanisms that may contribute to the observation of lower CRF levels in African American compared with Caucasian adults, including potential racial differences in physical activity levels, muscle fiber type distribution, and hemoglobin levels. If lower CRF is generally present in African Americans compared with Caucasians, and is of a clinically meaningful difference, this may represent an important public health concern.