Charles R. Gilkison

Amino acid supplementation increases lean body mass, basal muscle protein synthesis, and insulin-like growth factor-I expression in older women.

CONTEXT Inadequate dietary protein intake has been implicated in sarcopenia. OBJECTIVE AND DESIGN The objectives of this study were to determine whether: 1) chronic essential amino acid (EAA) supplementation improves postabsorptive muscle protein fractional synthesis rate (FSR), lean body mass (LBM), and one-repetition maximum muscle strength, and androgen receptor and IGF-I muscle protein expression; and 2) the acute anabolic response to EAA ingestion is preserved after a 3-month supplementation period. Using a randomized, double-blinded, placebo-controlled design, older women (68 +/- 2 yr) were assigned to receive either placebo (n = 7), or 15 g EAA/d [supplemented treatment group (SUP)] (n = 7) for 3 months. Metabolic outcomes were assessed in association with stable isotope studies conducted at 0 and 3 months. SETTING The study was performed at The University of Texas Medical Branch General Clinical Research Center. RESULTS Ingestion of 7.5 g EAA acutely stimulated FSR in both groups at 0 months (P < 0.05). Basal FSR at 3 months was increased in SUP only. The magnitude of the acute response to EAA was unaltered after 3 months in SUP. LBM increased in SUP only (P < 0.05). One-repetition maximum strength remained unchanged in both groups. Basal IGF-I protein expression increased in SUP after 3 months (P = 0.05), with no changes in androgen receptor or total and phosphorylated Akt, mammalian target of rapamycin, S6 kinase, and 4E-binding protein. CONCLUSIONS EAA improved LBM and basal muscle protein synthesis in older individuals. The acute anabolic response to EAA supplementation is maintained over time and can improve LBM, possibly offsetting the debilitating effects of sarcopenia.

Acanthosis Nigricans as a Risk Factor for Non-Insulin Dependent Diabetes Mellitus

The prevalences of obesity and of non-insulin dependent diabetes mellitus (NIDDM) have increased in the United States population over the past two decades, and thus diabetes preven tion has become a major concern of public health agencies such as the National Institutes of Health. Identification of individuals at risk for diabetes is an essential first step in designing and implementing intervention programs. Insulin resistance is the hallmark of the pathophysiology of NIDDM. Subjects with hyperinsulinemia, impaired glucose tolerance, or gestational diabetes are well accepted as being at high risk for diabetes. We propose that the easily identifiable skin lesion, acanthosis nigricans, is common in the major minority groups in the United States and that its presence is a surrogate for laboratory-determined hyperinsulinemia. Clin Pediatr. 1998;37:73-80

Effect of Growth Hormone Replacement Therapy on Cognition after Traumatic Brain Injury

Traumatic brain injury (TBI) is a major public health issue, and yet medical science has little to offer for the persistent symptoms that prevent many of these individuals from fully re-entering society. Post-traumatic hypopituitarism, and specifically growth hormone deficiency (GHD), has been found in a large percentage of individuals with chronic moderate to severe TBI. Presently, there are no published treatment studies of hormone replacement in this population. In this study, 83 subjects with chronic TBI were screened for hypopituitarism. Forty-two subjects were found to have either GHD or GH insufficiency (GHI), of which 23 agreed to be randomized to either a year of GH replacement or placebo. All subjects completed the study with no untoward side effects from treatment. A battery of neuropsychological tests and functional measures were administered before and after treatment. Improvement was seen on the following tests: Dominant Hand Finger Tapping Test, Wechsler Adult Intelligence Scale III-Information Processing Speed Index, California Verbal Learning Test II, and the Wisconsin Card Sorting Test (executive functioning). The findings of this pilot study provide preliminary evidence suggesting that some of the cognitive impairments observed in persons who are GHD/GHI after TBI may be partially reversible with appropriate GH replacement therapy.

A Randomized Pilot Study of Monthly Cycled Testosterone Replacement or Continuous Testosterone Replacement Versus Placebo in Older Men

CONTEXT Cycling androgens has been reported by athletes to improve physical performance by enhancing muscle mass and strength, a paradigm that has not been studied, and may have clinical value in older men being treated with testosterone. OBJECTIVE We investigated the efficacy of a monthly cycled testosterone regimen that uses half the testosterone dose as the current standard of care continuous therapy on body composition and muscle strength in older men. DESIGN, SETTING, AND PATIENTS Twenty-four community-dwelling older men 70 ± 2 yr of age with total testosterone levels below 500 ng/dl were randomized at the Institute for Translational Sciences-Clinical Research Center into a 5-month double-blind placebo-controlled trial. INTERVENTION Subjects were dosed weekly for 5 months, receiving continuous testosterone (TE, n = 8; 100 mg testosterone enanthate, im injection), monthly cycled testosterone (MO, n = 8; alternating months of testosterone and placebo), or placebo (PL, n = 8). MAIN OUTCOME MEASURES Main outcomes included body composition by dual-energy x-ray absorptiometry and upper and lower body muscle strength. Secondary outcomes included body weight, serum hormones, and mixed-muscle protein fractional synthesis rate (FSR). RESULTS Total lean body mass was increased and percent fat was reduced after 5 months in TE and MO (P < 0.05). Upper body muscle strength increased in TE, and lower body muscle strength increased in TE and MO (P < 0.05). FSR increased in TE and MO (P < 0.05) but not in PL. CONCLUSIONS Cycled testosterone improved body composition and increased muscle strength compared with placebo and increased FSR similarly to continuous testosterone.

Aerobic capacity and growth hormone deficiency after traumatic brain injury

CONTEXT GH deficiency occurs in approximately 20% of all individuals who suffer from a moderate to severe traumatic brain injury. OBJECTIVE This study determined whether GH deficiency secondary to traumatic brain injury had an effect on aerobic capacity. DESIGN Subjects were screened for GH deficiency by the glucagon stimulation test and performed a maximal treadmill exercise test. SETTING Patients were studied in the postacute recovery phase after traumatic brain injury. PARTICIPANTS Thirty-five individuals were studied. Groups were formed as follows: normal GH axis, greater than 8 ng/ml response (n = 12); insufficient, GH 3-8 ng/ml response (n = 11); and deficient, less than 3 ng/ml response (n = 12). INTERVENTION There was no intervention. MAIN OUTCOME MEASURE Aerobic capacity was assessed by measuring expired gases during a graded treadmill exercise test. One-way and two-way ANOVAs were carried out on all peak and submaximal cardiorespiratory variables, respectively. Appropriate post hoc comparisons followed as necessary. RESULTS Significantly higher peak oxygen consumption was found in traumatic brain injury subjects with GH normal vs. GH insufficient and deficient [26.4 +/- 6.9, 20.8 +/- 4.6, and 19.7 +/- 5.0, respectively (P < 0.05)]. Submaximal oxygen consumption was significantly higher in the GH normal group. All other variables were statistically similar. CONCLUSIONS This study shows that individuals with traumatic brain injury with normal GH secretion have below normal aerobic capacity and those patients who have GH insufficiency/deficiency are further deconditioned. Studies of GH replacement in these subjects should be conducted to assess whether GH therapy can improve cardiorespiratory fitness and prevent secondary disability.

Effect of recombinant growth hormone replacement in a growth hormone deficient subject recovering from mild traumatic brain injury: A case report.

Objective: To assess the effects of growth hormone (GH) replacement in an individual who sustained mild traumatic brain injury (mTBI) as an adult and was found to have GH deficiency by glucagon stimulation testing. Participant: A 43-year old woman who sustained a mild TBI at age 37 years. She was 6.8 years post-injury when she began supplementation. Intervention: Recombinant human GH (rhGH) subcutaneously per day for 1 year. Main outcome measures: Single fibre muscle function was evaluated from muscle biopsies. Body composition, muscle strength and peak aerobic capacity were also measured. In addition, neuropsychological tests of memory, processing speed and motor dexterity and speed, as well as a self-report depression inventory were administered. All assessments were performed at baseline and after 6 and 12 months of rhGH replacement therapy. Results: Single muscle fibre changes were greatest at 6 months. Body composition showed continuous improvement. Muscle strength improved for knee extension. Peak oxygen consumption increased at 6 months and total work and ventilatory equivalents continued to improve at 12 months. Significant improvements in neuropsychological test performance were not found, with the exception of performance on a test of motor dexterity and speed. Conclusion: rhGH replacement in a subject with GH deficiency after mild TBI improves muscle force production, body composition and aerobic capacity. Reliable improvements on tests of cognition were not found in this subject.

Getting the Story Straight: Evaluating the Test-Retest Reliability of a University Health History Questionnaire

This study was designed to establish the reliability of a health history questionnaire used as a screening tool for incoming university students. The authors used a test-retest design, with a test interval of 6 months, on a sample of medical and nursing students. The analysis focused on overall reliability of the questionnaire and reproducibility of specific items, based on question format. Questionnaire items of specific interest were those with dichotomous yes/no response options versus open-ended format questions, those using the words frequently or recently, or those that asked multiple questions. Demographic characteristics of the subjects were considered in the evaluation of reliability. Overall reliability of the questionnaire (93.6%) was above the anticipated level of 90%, and subject sex or program of study did not show any significant differences in reproducibility of responses. Although wording of questions did not affect item reliability, dichotomous format questions demonstrated a higher degree of reliability (96.4%) than the overall reliability of the questionnaire. Recommendations for enhancing the reliability of the questionnaire are based on item analysis and information gathered from interviews with subjects.

Functional Changes after Recombinant Human Growth Hormone Replacement in Patients with Chronic Traumatic Brain Injury and Abnormal Growth Hormone Secretion

We explored the effects of recombinant human growth hormone (rhGH) replacement on physical and cognitive functioning in subjects with a moderate-to-severe traumatic brain injury (TBI) with abnormal growth hormone (GH) secretion. Fifteen individuals who sustained a TBI at least 12 months prior to study enrollment were identified as having abnormal GH secretion by glucagon stimulation testing (maximum GH response less than 8 ng/mL). Peak cardiorespiratory capacity, body composition, and muscle force testing were assessed at baseline and one year after rhGH replacement. Additionally, standardized neuropsychological tests that assess memory, processing speed, and cognitive flexibility, as well as self-report inventories related to depression and fatigue, were administered at baseline and 1 year after rhGH replacement. Comparison tests were performed with proper post hoc analyses. All analyses were carried out at α < 0.05. Peak O2 consumption, peak oxygen pulse (estimate of cardiac stroke volume), and peak ventilation all significantly increased (p < 0.05). Maximal isometric and isokinetic force production were not altered. Skeletal muscle fatigue did not change but the perceptual rating of fatigue was reduced by ∼25% (p = 0.06). Cognitive performance did not change significantly over time, whereas self-reported symptoms related to depression and fatigue significantly improved. The observed changes suggest that rhGH replacement has a positive impact on cardiorespiratory fitness and a positive impact on perceptual fatigue in survivors of TBI with altered GH secretion.

EFFECT OF ADDING A SULFONYLUREA IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES MELLITUS PREVIOUSLY WELL CONTROLLED WITH INSULIN

OBJECTIVE To determine whether insulin-requiring patients with non-insulin-dependent diabetes mellitus (NIDDM) and good glycemic control would benefit in weight control, serum lipid concentrations, or blood pressure from a reduction in exogenous insulin treatment. METHODS Eighteen patients with well-controlled NIDDM who required insulin therapy were entered into a randomized, placebo-controlled, double-blind, crossover study of the addition for 12 weeks of treatment with a second-generation sulfonylurea agent (micronized glyburide). RESULTS The mean fasting plasma glucose at entry was 7.00 +/- 0.22 mmol/L and at the end of the 12-week treatment phase was 7.67 +/- 0.39 mmol/L with placebo and 7.28 +/- 0.44 mmol/L with active drug. Hemoglobin A(1c) was unchanged during the study (7.5 +/- 0.2% at entry, 7.5 +/- 0.3% with placebo, and 7.4 +/- 0.3% with active drug). Addition of the orally administered agent resulted in a 29% decrease in exogenous insulin requirements and a 37% increase in 24-hour urinary C-peptide excretion. Patients had no change in weight after 12 weeks of either placebo or active drug. Plasma cholesterol levels declined slightly during the study, but they did not differ significantly during drug and placebo treatment. Blood pressure was unchanged in both the subjects with and without hypertension. CONCLUSION In patients with NIDDM and good glycemic control with insulin treatment, a glyburide-related increase in endogenous insulin secretion caused a proportionate decrease in exogenous insulin requirements. With continued good glycemic control, however, the orally administered agent showed no additional benefit on weight, blood pressure, plasma triglycerides, or low-density lipoprotein or high-density lipoprotein cholesterol.

Efficacy of Testosterone plus NASA Exercise Countermeasures during Head-Down Bed Rest

Introduction Prolonged confinement to head-down bed rest (HDBR) results in musculoskeletal losses similar to those observed during long-duration space flight. Exercise countermeasures by themselves have not completely prevented the deleterious losses in muscle mass or function in HDBR or space flight. Purpose The objective was to investigate the safety and efficacy of intermittent, low-dose testosterone treatment in conjunction with NASA exercise (SPRINT) countermeasures during 70 d of 6° HDBR. Methods Healthy men (35 ± 8 yr) were randomized into one of three groups that remained inactive (CON) or performed exercise 6 d·wk−1 in addition to receiving either placebo (PEX) or testosterone treatment (TEX, 100 mg·wk−1). Testosterone/placebo injections were administered once a week for 2 wk, followed by 2 wk off and so on, during HDBR. Results Total, leg, and trunk lean body mass (LBM) consistently decreased in CON, increased in TEX, and had little or no changes in PEX. Total, leg, and trunk fat mass consistently increased in CON and PEX and decreased in TEX. Leg strength decreased in CON, whereas PEX and TEX were protected against loss in strength. Changes in leg LBM correlated positively with changes in leg muscle strength. Conclusions Addition of a testosterone countermeasure enhanced the preventative actions of exercise against body composition changes during long-term HDBR in healthy eugonadal men. This is the first report to demonstrate that cycled, low-dose testosterone treatment increases LBM under conditions of strict exercise control. These results are clinically relevant to the development of safe and effective therapies against muscle atrophy during long-term bed rest, aging, and disease where loss of muscle mass and strength is a risk. The potential space flight applications of such countermeasure combinations deserve further investigations.