Urine creatinine concentration and clinical outcomes in older adults: The Cardiovascular Health Study.

PURPOSE: Loss of muscle mass and strength are associated with long-term adverse health outcomes in older adults. Urine creatinine concentrations (Ucr; mg/dl) are a measure of muscle tissue mass and turnover. This study assessed the associations of a spot Ucr level with muscle mass and with risk of hospitalization, mortality, and diabetes mellitus in older adults. METHODS: We examined 3424 participants from the Cardiovascular Health Study who provided spot urine samples in 1996-1997 and who were followed through June 2015. All participants underwent baseline measurement of grip strength. In a sub-cohort, 1331 participants underwent dual energy X-ray absorptiometry (DEXA) scans, from which lean muscle mass was derived. Participants were followed for a median of 10 years for hospitalizations and mortality, and 9 years for diabetes mellitus. RESULTS: In linear regression analysis, a one standard deviation higher Ucr concentration (64.6 mg/dl) was associated with greater grip strength (kg force) ß = 0.44 [0.16, 0.72]; p = 0.002) and higher lean muscle mass (kg) (ß = 0.43 [0.08, 0.78]; p = 0.02). In Cox regression analyses, each standard deviation greater Ucr concentration was associated with lower rates of hospitalizations (0.94 [95% confidence interval, 0.90, 0.98]; p < 0.001) and lower mortality risk (0.92 [0.88, 0.97]; p < 0.001), while a one standard deviation increase in muscle mass derived from DEXA had no such significant association. Ucr levels were not associated with incident diabetes mellitus risk (0.97 [0.85, 1.11]; p = 0.65). CONCLUSION: A higher spot Ucr concentration was favorably associated with muscle mass and strength and with health outcomes in older community-living adults. The ease of obtaining a spot Ucr makes it an attractive analyte to use for gauging the health of older adults.

Exploration of muscle loss and metabolic state during prolonged critical illness: Implications for intervention?

BACKGROUND: Muscle wasting in the critically ill is up to 2% per day and delays patient recovery and rehabilitation. It is linked to inflammation, organ failure and severity of illness. The aims of this study were to understand the relationship between muscle depth loss, and nutritional and inflammatory markers during prolonged critical illness. Secondly, to identify when during critical illness catabolism might decrease, such that targeted nutritional strategies may logically be initiated. METHODS: This study was conducted in adult intensive care units in two large teaching hospitals. Patients anticipated to be ventilated for >48 hours were included. Serum C-reactive protein (mg/L), urinary urea (mmol/24h), 3-methylhistidine (µmol/24h) and nitrogen balance (g/24h) were measured on days 1, 3, 7 and 14 of the study. Muscle depth (cm) on ultrasound were measured on the same days over the bicep (bicep and brachialis muscle), forearm (flexor compartment of muscle) and thigh (rectus femoris and vastus intermedius). RESULTS: Seventy-eight critically ill patients were included with mean age of 59 years (SD: 16) and median Intensive care unit (ICU) length of stay of 10 days (IQR: 6-16). Starting muscle depth, 8.5cm (SD: 3.2) to end muscle depth, 6.8cm (SD: 2.2) were on average significantly different over 14 days, with mean difference -1.67cm (95%CI: -2.3 to -1cm), p<0.0001. Protein breakdown and inflammation continued over 14 days of the study. CONCLUSION: Our patients demonstrated a continuous muscle depth loss and negative nitrogen balance over the 14 days of the study. Catabolism remained dominant throughout the study period. No obvious 'nutritional tipping point" to identify anabolism or recovery could be identified in our cohort. Our ICU patient cohort is one with a moderately prolonged stay. This group showed little consistency in data, reflecting the individuality of both disease and response. The data are consistent with a conclusion that a time based assumption of a tipping point does not exist. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN79066838. Registration 25 July 2012.

Dietary Protein Sources and Muscle Mass over the Life Course: The Lifelines Cohort Study.

The influence of dietary protein intake on muscle mass in adults remains unclear. Our objective was to investigate the association between protein intake and muscle mass in 31,278 men and 45,355 women from the Lifelines Cohort. Protein intake was estimated by food frequency questionnaire and muscle mass was estimated from 24 h urinary creatinine excretion. The age range was 18⁻91 years and mean total protein intake was 1.0 ± 0.3 g/kg/day. Across increasing quartiles of total protein intake, animal protein intake, and fish/meat/egg protein intake, creatinine excretion significantly increased in both men (+4% for total and +6% for fish/meat/egg protein intake, p < 0.001) and women (+3% for total and +6% for fish/meat/egg protein intake, p < 0.001). The associations were not systematically stronger or weaker with increasing age, but associations were strongest for young men (26⁻45 years) and older women (>75 years). The association between total protein intake and muscle mass was dependent on physical activity in women (p interaction < 0.001). This study suggests that total protein intake, animal protein intake, and in particular fish/meat/egg protein intake may be important for building and preserving muscle mass. Dietary protein sources should be further studied for their potential to build and preserve muscle mass.

Dietary animal protein intake: association with muscle mass index in older women.

BACKGROUND: Aging is associated with reductions in muscle mass and strength, so-called sarcopenia, and is generally characterized using muscle mass index (MMI = FFM (kg)/height (m)2). It is believed that adequate nutrition especially regarding protein intake, can delay this progression and enhance the quality of life of elders. OBJECTIVES: We examined whether the predominant source of protein consumed (animal or vegetal) by older women was associated with MMI. DESIGN: Thirty-eight healthy, normal weight, sedentary women, aged between 57-75 years (mean age: 66 +/- 5 years old), and taking no medication that could influence metabolism were recruited. Body composition was measured by dual-energy X-ray absorptiometry; muscle protein content was measured by the use of creatinine excretion. Physical activity metabolism was obtained by the use of accelerometry, and indirect calorimetry. Finally, protein intake was measured with a 3-day dietary record. RESULTS: Significant correlations were observed between MMI and body mass index, fat-free mass, muscle protein content, total protein intake, animal protein intake, fat mass, visceral fat and daily energy expenditure. However, a stepwise regression analysis showed animal protein intake to be the only independent predictor of MMI (r2=0.19; p=0.008). CONCLUSIONS: Our results suggest that protein intake, especially from animal sources, may be associated with a better preservation of MMI. However, more research is needed to confirm our results.

Rate of urinary urea output correlates to degree of muscular atrophy induced by triamcinolone acetonide.

1. The effect of administering triamcinolone acetonide (10 mg kg-1 day-1) as seven consecutive single daily subcutaneous injections on urinary urea output and muscular atrophy was studied in rabbits. 2. The ratio of the wet weight of the lateral vastus of the quadriceps muscle to body weight (MI) varied greatly among the rabbits. 3. The ratio of urinary urea output after to before triamcinolone injection correlated significantly to MI. 4. These findings suggest that the ratio of urinary urea output can be used as a predictive index for steroid myopathy.

Dicarboxylic aciduria in an infant with spinal muscular atrophy.

A 1-year-old infant with classic Werdnig-Hoffmann disease was found to excrete abnormally large amounts of dicarboxylic acids in both fed and fasting states, with especially notable increases in the longer-chain (C10 and C12) 3-hydroxydicarboxylic acids. Dicarboxylic aciduria has not previously been associated with Werdnig-Hoffmann disease and suggests a primary or secondary defect of fatty acid metabolism in the disorder.

Skeletal muscle catabolism in amyotrophic lateral sclerosis and chronic spinal muscular atrophy.

ALS and chronic spinal muscular atrophy are characterized by wasting of skeletal muscle, suggesting accelerated catabolism or reduced synthesis of muscle protein. We studied seven patients with ALS and three with chronic spinal muscular atrophy using 24-hour urinary 3-methylhistidine excretion as a measure of the rate of muscle catabolism and 24-hour urinary creatinine excretion as an index of significantly and similarly higher in both groups of patients than in controls (p less than 0.0005), implying a state of accelerated skeletal muscle protein catabolism in these diseases.

[Diabetic amyotrophy--a polygenetic syndrome (author's transl)]. / Die diabetische Amyotrophie--ein polygenetisches Syndrom.

Detailed clinical and biochemical investigations were done in 14 patients with the syndrome of diabetic amyotrophy. Three patients suffered from manifest insulin-dependent diabetes, five had only diminished glucose tolerance. Simultaneously, excretion of creatinine was reduced indicating reduction of healthy muscle mass. In these cases disturbance of glucose tolerance must be considered symptom and not cause of amyotrophy. Further investigations revealed neoplasia (n = 2), generalised amyloidosis (n = 3), polycythaemia vera (n = 1), chronic infectious disease (n = 3), and motor neuron degeneration (n = 3). The attribute "diabetic" must not bea considered representing a single cause in this connection. With treatment aimed at more than one factor, satisfactory results of therapy may be expected in the majority of cases.

[Use of lithium carbonate to treat Kugelberg--Welander spinal amyotrophy]. / Primenenie uglekislogo litiia dlia lecheniia spinal'noi amiotrofii Kugel'berga--Velandera.

On the basis of data on disturbances of the metabolism of cyclic 3',5'-adenosine monophosphate in patients with Kugelberg-Welander's amyotrophy it is suggested that lithium carbonate which is an inhibitor of adenylcyclase should be used as a medicine. It was shown that the drug exerted a stabilizing influence on the pathological process. Positive clinical and biochemical changes due to the application of lithium carbonate are noted.

[Aminoacid levels in Werding-Hoffmann and Kugelberg-Welander diseases (author's transl)]. / Alterazioni degli aminoacidi nella malattia di Werdnig-Hoffmann: studio comparativo con la malattia di Kugelberg-Welander.

The concentration of free aminoacids in plasma and urine were estimated in 10 patients suffering from Werdnig-Hoffmann's disease of long duration. The age of the patients was between 5 and 14 years. Estimations were also made in 10 patients with Kugelberg-Welander's disease aged between 11 and 34 years. The aminoacid concentrations were estimated on samples of plasma and 24 hours samples of urine by means of chromatography on ion-exchange resins. The data obtained were compared respectively with groups of thirty and ten healthy subjects of the same age. In the group of patients with Werdnig-Hoffmann's disease a significant increase of taurine (p less than 0.001) and of glutamic acid (p less than 0.001) was found in the plasma. The urinary excretion of glutamine was increased in the same group of patients (p less than 0.001) and in the group with Kugelberg-Welander's disease (p less than 0.005). These aminoacid levels are interpreted as an expression of a reduced oxygen metabolism and increased proteolysis in the skeletal muscles in conditions of chronic denervation.

Effect of 14 days of bed rest on urine metabolite excretion and plasma enzyme levels.

After one week of ambulatory baseline measurement, a group of eight men 19-26 years of age remained continuously recumbent for 14 days. Studies were continued for one week following the prolonged recumbency. Urine excretion rates for a number of constituents were determined 2 days before bed rest, on day 14 of bed rest, and day 6 after bed rest. Blood plasma samples were also obtained at these times, and analyzed for several enzymes. On day 14 of bed rest significant increases were observed in urine excretion of total osmotically active substances, magnesium, calcium, phosphate, creatinine, hydroxyproline, and 17-OH corticosteroids. A decrease occurred in urinary glucose excretion. Plasma levels of alkaline phosphatase and LDH-3 were depressed, while plasma GPT was elevated. Many of these changes persisted on day 6 after bed rest, and are interpreted as concomitants of the disuse atrophy of the musculoskeletal system that characterizes prolonged bed rest and weightlessness.