Prolonged leucine supplementation does not augment muscle mass or affect glycemic control in elderly type 2 diabetic men.

The loss of muscle mass with aging has been, at least partly, attributed to a blunted muscle protein synthetic response to food intake. Leucine coingestion has been reported to stimulate postprandial insulin release and augment postprandial muscle protein accretion. We assessed the clinical benefits of 6 mo of leucine supplementation in elderly, type 2 diabetes patients. Sixty elderly males with type 2 diabetes (age, 71 ± 1 y; BMI, 27.3 ± 0.4 kg/m(2)) were administered 2.5 g L-leucine (n = 30) or a placebo (n = 30) with each main meal during 6 mo of nutritional intervention (7.5 g/d leucine or placebo). Body composition, muscle fiber characteristics, muscle strength, glucose homeostasis, and basal plasma amino acid and lipid concentrations were assessed prior to, during, and after intervention. Lean tissue mass did not change or differ between groups and at 0, 3, and 6 mo were 61.9 ± 1.1, 62.2 ± 1.1, and 62.0 ± 1.0 kg, respectively, in the leucine group and 62.2 ± 1.3, 62.2 ± 1.3, and 62.2 ± 1.3 kg in the placebo group. There also were no changes in body fat percentage, muscle strength, and muscle fiber type characteristics. Blood glycosylated hemoglobin did not change or differ between groups and was 7.1 ± 0.1% in the leucine group and 7.2 ± 0.2% in the placebo group. Consistent with this, oral glucose insulin sensitivity and plasma lipid concentrations did not change or differ between groups. We conclude that prolonged leucine supplementation (7.5 g/d) does not modulate body composition, muscle mass, strength, glycemic control, and/or lipidemia in elderly, type 2 diabetes patients who habitually consume adequate dietary protein.

Reduction of cardiovascular event rate: different effects of cardiac rehabilitation in CABG and PCI patients.

OBJECTIVE: In coronary artery disease, the implementation of a cardiac rehabilitation (CR) programme favourably affects cardiovascular prognosis. However, it remains uncertain whether patients benefit to a similar extent from CR after coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI). In this study, we have assessed whether CR is equally effective for suppressing the two-year cardiovascular event incidence after CABG or PCI. METHODS AND RESULTS: 194 PCI and 149 CABG patients participated in a three-month CR programme, while 245 PCI and 89 CABG patients received standard care. After the completion of CR during a two-year follow-up, data on cardiovascular risk factors, medication and cardiovascular events (repeat coronary revascularisation, acute myocardial infarction, and death) were collected from hospital files. Both CABG and PCI patients included into CR showed a significantly lower mortality, as compared to control patients (0.6% vs. 4.2%, P < 0.05). However, total cardiovascular disease incidence was significantly lower as a result of CR in CABG patients (4.7% vs. 14.0%, P < 0.05), but not in PCI patients (19.1% vs. 22.4%, P > 0.05). CONCLUSION: When following a similar 3-month cardiac rehabilitation programme, the reduction of cardiovascular disease incidence during 2 years of follow-up is different between PCI and CABG patients.

Muscle fibre capillarization is a critical factor in muscle fibre hypertrophy during resistance exercise training in older men.

BACKGROUND: Adequate muscle fibre perfusion is critical for the maintenance of muscle mass; it is essential in the rapid delivery of oxygen, nutrients and growth factors to the muscle, stimulating muscle fibre growth. Muscle fibre capillarization is known to decrease substantially with advancing age. However, whether (relative) low muscle fibre capillarization negatively impacts the muscle hypertrophic response following resistance exercise training in older adults is unknown. METHODS: Twenty-two healthy older men (71 ± 1 years) performed 24 weeks of progressive resistance type exercise training. To assess the change in muscle fibre characteristics, percutaneous biopsies from the vastus lateralis muscle were taken before and following 12 and 24 weeks of the intervention programme. A comparison was made between participants who had a relatively low type II muscle fibre capillary-to-fibre perimeter exchange index (CFPE; LOW group) and high type II muscle fibre CFPE (HIGH group) at baseline. Type I and type II muscle fibre size, satellite cell, capillary content and distance between satellite cells to the nearest capillary were determined by immunohistochemistry. RESULTS: Overall, type II muscle fibre size (from 5150 ± 234 to 6719 ± 446 µm2 , P < 0.05) and satellite cell content (from 0.058 ± 0.006 to 0.090 ± 0.010 satellite cells per muscle fibre, P < 0.05) had increased significantly in response to 24 weeks of resistance exercise training. However, these improvements where mainly driven by differences in baseline type II muscle fibre capillarization, whereas muscle fibre size (from 5170 ± 390 to 7133 ± 314 µm2 , P < 0.05) and satellite cell content (from 0.059 ± 0.009 to 0.102 ± 0.017 satellite cells per muscle fibre, P < 0.05) increased significantly in the HIGH group, no significant changes were observed in LOW group following exercise training. No significant changes in type I and type II muscle fibre capillarization were observed in response to 12 and 24 weeks of resistance exercise training in both the LOW and HIGH group. CONCLUSIONS: Type II muscle fibre capillarization at baseline may be a critical factor for allowing muscle fibre hypertrophy to occur during prolonged resistance exercise training in older men.

Extensive Type II Muscle Fiber Atrophy in Elderly Female Hip Fracture Patients.

BACKGROUND: Sarcopenia, or the loss of muscle mass and strength, is known to increase the risk for falls and (hip) fractures in older people. The objective of this study was to assess the skeletal muscle fiber characteristics in elderly female hip fracture patients. METHOD: Percutaneous needle biopsies were collected from the vastus lateralis muscle in 15 healthy young women (20 ± 0.4 years), 15 healthy elderly women (79 ± 1.7 years), and 15 elderly women with a fall-related hip fracture (82 ± 1.5 years). Immunohistochemical analyses were performed to assess Type I and Type II muscle fiber size, and myonuclear and satellite cell content. RESULTS: Type II muscle fiber size was significantly different between all groups (p < .05), with smaller Type II muscle fibers in the hip fracture patients (2,609 ± 185 µm2) compared with healthy elderly group (3,723 ± 322 µm2) and the largest Type II muscle fibers in the healthy young group (4,755 ± 335 µm2). Furthermore, Type I muscle fiber size was significantly lower in the hip fracture patients (4,684 ± 211 µm2) compared with the healthy elderly group (5,842 ± 316 µm2, p = .02). The number of myonuclei per Type II muscle fiber was significantly lower in the healthy elderly and hip fracture group compared with the healthy young group (p = .011 and p = .002, respectively). Muscle fiber satellite cell content did not differ between groups. CONCLUSION: Elderly female hip fracture patients show extensive Type II muscle fiber atrophy when compared with healthy young or age-matched healthy elderly controls. Type II muscle fiber atrophy is an important hallmark of sarcopenia and may predispose to falls and (hip) fractures in the older population.

There Are No Nonresponders to Resistance-Type Exercise Training in Older Men and Women.

OBJECTIVE: To assess the proposed prevalence of unresponsiveness of older men and women to augment lean body mass, muscle fiber size, muscle strength, and/or physical function following prolonged resistance-type exercise training. DESIGN/SETTING/PARTICIPANTS: A retrospective analysis of the adaptive response to 12 (n = 110) and 24 (n = 85) weeks of supervised resistance-type exercise training in older (>65 years) men and women. MEASUREMENTS: Lean body mass (DXA), type I and type II muscle fiber size (biopsy), leg strength (1-RM on leg press and leg extension), and physical function (chair-rise time) were assessed at baseline, and after 12 and 24 weeks of resistance-type exercise training. RESULTS: Lean body mass increased by 0.9 ± 0.1 kg (range: -3.3 to +5.4 kg; P < .001) from 0 to 12 weeks of training. From 0 to 24 weeks, lean body mass increased by 1.1 ± 0.2 kg (range: -1.8 to +9.2 kg; P < .001). Type I and II muscle fiber size increased by 324 ± 137 µm(2) (range: -4458 to +3386 µm(2); P = .021), and 701 ± 137 µm(2) (range: -4041 to +3904 µm(2); P < .001) from 0 to 12 weeks. From 0 to 24 weeks, type I and II muscle fiber size increased by 360 ± 157 µm(2) (range: -3531 to +3426 µm(2); P = .026) and 779 ± 161 µm(2) (range: -2728 to +3815 µm(2); P < .001). The 1-RM strength on the leg press and leg extension increased by 33 ± 2 kg (range: -36 to +87 kg; P < .001) and 20 ± 1 kg (range: -22 to +56 kg; P < .001) from 0 to 12 weeks. From 0 to 24 weeks, leg press and leg extension 1-RM increased by 50 ± 3 kg (range: -28 to +145 kg; P < .001) and 29 ± 2 kg (range: -19 to +60 kg; P < .001). Chair-rise time decreased by 1.3 ± 0.4 seconds (range: +21.6 to -12.5 seconds; P = .003) from 0 to 12 weeks. From 0 to 24 weeks, chair-rise time decreased by 2.3 ± 0.4 seconds (range: +10.5 to -23.0 seconds; P < .001). Nonresponsiveness was not apparent in any subject, as a positive adaptive response on at least one training outcome was apparent in every subject. CONCLUSIONS: A large heterogeneity was apparent in the adaptive response to prolonged resistance-type exercise training when changes in lean body mass, muscle fiber size, strength, and physical function were assessed in older men and women. The level of responsiveness was strongly affected by the duration of the exercise intervention, with more positive responses following more prolonged exercise training. We conclude that there are no nonresponders to the benefits of resistance-type exercise training on lean body mass, fiber size, strength, or function in the older population. Consequently, resistance-type exercise should be promoted without restriction to support healthy aging in the older population.

The effect of exercise training on the course of cardiac troponin T and I levels: three independent training studies.

With the introduction of high-sensitive assays, cardiac troponins became potential biomarkers for risk stratification and prognostic medicine. Observational studies have reported an inverse association between physical activity and basal cardiac troponin levels. However, causality has never been demonstrated. This study investigated whether basal cardiac troponin concentrations are receptive to lifestyle interventions such as exercise training. Basal high-sensitive cardiac troponin T (cTnT ) and I (cTnI) were monitored in two resistance-type exercise training programs (12-week (study 1) and 24-week (study 2)) in older adults (≥65 years). In addition, a retrospective analysis for high sensitive troponin I in a 24-week exercise controlled trial in (pre)frail older adults was performed (study 3). In total, 91 subjects were included in the final data analyses. There were no significant changes in cardiac troponin levels over time in study 1 and 2 (study 1: cTnT -0.13 (-0.33-+0.08) ng/L/12-weeks, cTnI -0.10 (-0.33-+0.12) ng/L/12-weeks; study 2: cTnT -1.99 (-4.79-+0.81) ng/L/24-weeks, cTnI -1.59 (-5.70-+2.51) ng/L/24-weeks). Neither was there a significant interaction between training and the course of cardiac troponin in study 3 (p = 0.27). In conclusion, this study provides no evidence that prolonged resistance-type exercise training can modulate basal cardiac troponin levels.

Elderly men and women benefit equally from prolonged resistance-type exercise training.

This study compares the effects of 6 months resistance-type exercise training (three times per week) between healthy elderly women (n = 24; 71±1 years) and men (n = 29; 70±1 years). Muscle mass (dual-energy x-ray absorptiometry-computed tomography), strength (one-repetition maximum), functional capacity (sit-to-stand time), muscle fiber characteristics (muscle biopsies), and metabolic profile (blood samples) were assessed. Leg lean mass (3% ± 1%) and quadriceps cross-sectional area (9% ± 1%) increased similarly in both groups. One-repetition maximum leg extension strength increased by 42% ± 3% (women) and 43% ± 3% (men). Following training, type II muscle fiber size had increased, and a type II muscle fiber specific increase in myonuclear and satellite cell content was observed with no differences between genders. Sit-to-stand time decreased similarly in both groups. Glycemic control and blood lipid profiles improved to a similar extent in both women and men. A generic resistance-type exercise training program can be applied for both women and men to effectively counteract the loss of muscle mass and strength with aging.

The decline in skeletal muscle mass with aging is mainly attributed to a reduction in type II muscle fiber size.

BACKGROUND: The loss of skeletal muscle mass with aging has been attributed to a decline in muscle fiber number and muscle fiber size. OBJECTIVE: To define to what extent differences in leg muscle cross-sectional area (CSA) between young and elderly men are attributed to differences in muscle fiber size. METHODS: Quadriceps muscle CSA and type I and type II muscle fiber size were measured in healthy young (n=25; 23 ± 1 y) and older (n=26; 71 ± 1 y) men. Subsequently, the older subjects performed 6 months of resistance type exercise training, after which measurements were repeated. Differences in quadriceps muscle CSA were compared with differences in type I and type II muscle fiber size. RESULTS: Quadriceps CSA was substantially smaller in older versus young men (68 ± 2 vs 80 ± 2 cm(2), respectively; P<0.001). Type II muscle fiber size was substantially smaller in the elderly vs the young (29%; P<0.001), with a tendency of smaller type I muscle fibers (P=0.052). Differences in type II muscle fiber size fully explained differences in quadriceps CSA between groups. Prolonged resistance type exercise training in the elderly increased type II muscle fiber size by 24 ± 8% (P<0.01), explaining 100 ± 3% of the increase in quadriceps muscle CSA (from 68 ± 2 to 74 ± 2 cm(2)). CONCLUSION: Reduced muscle mass with aging is mainly attributed to smaller type II muscle fiber size and, as such, is unlikely accompanied by substantial muscle fiber loss. In line, the increase in muscle mass following prolonged resistance type exercise training can be attributed entirely to specific type II muscle fiber hypertrophy.

Patients with type 2 diabetes show a greater decline in muscle mass, muscle strength, and functional capacity with aging.

BACKGROUND: The loss of muscle mass with aging reduces muscle strength, impairs functional capacity, and increases the risk of developing chronic metabolic disease. It has been suggested that the development of type 2 diabetes results in a more rapid decline in muscle mass, strength, and functional capacity. OBJECTIVE: To investigate the impact of type 2 diabetes on muscle mass, strength, and functional capacity in an older population. METHODS: Muscle mass (DXA and muscle biopsies), strength (1-repetition maximum), functional capacity (sit-to-stand test and handgrip strength), and reaction time performance (computer task) were compared between 60 older men with type 2 diabetes (71 ± 1 years) and 32 age-matched normoglycemic controls (70 ± 1 years). Data were analyzed using ANCOVA to adjust for several potential confounders. RESULTS: Leg lean mass and appendicular skeletal muscle mass were significantly lower in older men with type 2 diabetes (19.1 ± 0.3 and 25.9 ± 0.4 kg, respectively) compared with normoglycemic controls (19.7 ± 0.3 and 26.7 ± 0.5 kg, respectively). Additionally, leg extension strength was significantly lower in the group with type 2 diabetes (84 ± 2 vs 91 ± 2 kg, respectively). In agreement, functional performance was impaired in the men with type 2 diabetes, with longer sit-to-stand time (9.1 ± 0.4 vs 7.8 ± 0.3 seconds) and lower handgrip strength (39.5 ± 5.8 vs 44.6 ± 6.1 kg) when compared with normoglycemic controls. However, muscle fiber size and reaction time performance did not differ between groups. CONCLUSION: Older patients with type 2 diabetes show an accelerated decline in leg lean mass, muscle strength, and functional capacity when compared with normoglycemic controls. Exercise intervention programs should be individualized to specifically target muscle mass, strength, and functional capacity in the older population with type 2 diabetes.

Protein supplementation during resistance-type exercise training in the elderly.

INTRODUCTION: Resistance training has been well established as an effective treatment strategy to increase skeletal muscle mass and strength in the elderly. We assessed whether dietary protein supplementation can further augment the adaptive response to prolonged resistance-type exercise training in healthy elderly men and women. METHODS: Healthy elderly men (n = 31, 70 ± 1 yr) and women (n = 29, 70 ± 1 yr) were randomly assigned to a progressive, 24-wk resistance-type exercise training program with or without additional protein supplementation (15 g·d-1). Muscle hypertrophy was assessed on a whole-body Dual-energy X-ray absorptiometry (DXA), limb (computed tomography), and muscle fiber (biopsy) level. Strength was assessed regularly by 1-repetition maximum (RM) strength testing. Functional capacity was assessed with a sit-to-stand and handgrip test. RESULTS: One-RM strength increased by 45% ± 6% versus 40% ± 3% (women) and 41% ± 4% versus 44% ± 3% (men) in the placebo versus protein group, respectively (P < 0.001), with no differences between groups. Leg muscle mass (women, 4% ± 1% vs 3% ± 1%; men, 3% ± 1% vs 3% ± 1%) and quadriceps cross-sectional area (women, 9% ± 1% vs 9% ± 1%; men, 9% ± 1% vs 10% ± 1%) increased similarly in the placebo versus protein groups (P < 0.001). Type II muscle fiber size increased over time in both placebo and protein groups (25% ± 13% vs 30% ± 9% and 23% ± 12% vs 22% ± 10% in the women and men, respectively). Sit-to-stand improved by 18% ± 2% and 19% ± 2% in women and men, respectively (P < 0.001). CONCLUSION: Prolonged resistance-type exercise training increases skeletal muscle mass and strength, augments functional capacity, improves glycemia and lipidemia, and reduces blood pressure in healthy elderly men and women. Additional protein supplementation (15 g·d-1) does not further increase muscle mass, strength, and/or functional capacity.

Leucine as a pharmaconutrient to prevent and treat sarcopenia and type 2 diabetes.

Amino acids function as precursors for de novo protein synthesis. In addition, however, they play a key role as nutritional signals that regulate multiple cellular processes. There is ample in vitro and in vivo evidence showing that muscle tissue responds to increases in amino acid availability via signal transduction pathways that are also regulated by insulin, glucagon, growth hormone, and insulin growth factor 1. The increased amino acid availibility results in the upregulation of mRNA translation, thereby increasing muscle protein synthesis, which, in turn, leads to greater net muscle protein accretion. These findings have been particularly pronounced for the amino acid leucine. Furthermore, leucine has the ability to act as a strong insulin secretagogue. Consequently, it has been suggested that leucine represents an effective pharmaconutrient for the prevention and treatment of sarcopenia and type 2 diabetes. In accordance, recent in vivo studies in humans show that free leucine ingestion can reverse the blunted response of muscle protein synthesis to amino acid/protein intake in the elderly. Although short-term studies suggest that leucine supplementation can stimulate muscle mass accretion in the elderly, there are no long-term nutritional intervention studies to confirm this or the other proposed benefits of leucine as a pharmaconutrient.