Hormone replacement therapy and physical function in healthy older men. Time to talk hormones?

Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established.     

Interpreting oral health-related quality of life data

The most common way of presenting data from studies using quality of life or patient-based outcome (PBO) measures is in terms of mean scores along with testing the statistical significance of differences in means. We argue that this is insufficient in and of itself and call for a more comprehensive and thoughtful approach to the reporting and interpretation of data. PBO scores (and their means for that matter) are intrinsically meaningless, and differences in means between groups mask important and potentially different patterns in response within groups. More importantly, they are difficult to interpret because of the absence of a meaningful benchmark. The minimally important difference (MID) provides that benchmark to assist interpretability. This commentary discusses different approaches (distribution-based and anchor-based) and specific methods for assessing the MID in both longitudinal and cross-sectional studies, and suggests minimum standards for reporting and interpreting PBO measures in an oral health context.     

Whole-body vibration in addition to strength and balance exercise for falls-related functional mobility of frail older adults: a single-blind randomized controlled trial

Objectives: To investigate the effects of whole-body vibration in addition to an exercise programme on functional mobility and related outcomes for frail older fallers. Design: Single-blind randomized parallel group trial. Setting: UK; National Health Service assessment and rehabilitation facility for older people. Participants: Frail older fallers: 38 (80 ± 8.6 years) performed the exercise with whole-body vibration (vibration group), and 39 (82 ± 8.1 years) without (exercise group). Intervention: Sixty minutes supervised exercise class three times weekly for eight weeks ± whole-body vibration (up to 5 × 1 minute, 15-30 Hz and 2-8 mm peak-to-peak). Measurements: Timed Up and Go, 6-m walk, static balance, fear of falling (FES-I) and self-reported health status (SF-12 version 2) were assessed at baseline, four weeks (mobility measures only), eight weeks and six months. Results: Timed Up and Go and 6-m walk improved in both groups at eight weeks (P < 0.01), but significantly more in the vibration group (timed up and go: 38 vs. 20%, P < 0.05); 6-m walk: (36 vs. 18.1%, P < 0.05, respectively). Balance, fear of falling and physical component of the self-reported health status improved similarly in both groups (P < 0.05). At follow-up, no significant differences from baseline remained for any measure. The mean total time experienced was 37% of maximal target. Conclusion: The addition of whole-body vibration to strength and balance exercise resulted in greater improvements in functional mobility than exercise alone, despite achieving lower than anticipated exposure. Gains from neither intervention were sustained at six months.     

Novel glucagon-like peptide-1 (GLP-1) analog (Val8)GLP-1 results in significant improvements of glucose tolerance and pancreatic beta-cell function after 3-week daily administration in obese diabetic (ob/ob) mice

This study evaluates the antidiabetic potential of an enzyme-resistant analog, (Val8)GLP-1. The effects of daily administration of a novel dipeptidyl peptidase IV-resistant glucagon-like peptide-1 (GLP-1) analog, (Val8)GLP-1, on glucose tolerance and pancreatic beta-cell function were examined in obese-diabetic (ob/ob) mice. Acute intraperitoneal administration of (Val8)GLP-1 (6.25-25 nmol/kg) with glucose increased the insulin response and reduced the glycemic excursion in a dose-dependent manner. The effects of (Val8)GLP-1 were greater and longer lasting than native GLP-1. Once-daily subcutaneous administration of (Val8)GLP-1 (25 nmol/kg) for 21 days reduced plasma glucose concentrations, increased plasma insulin, and reduced body weight more than native GLP-1 without a significant change in daily food intake. Furthermore, (Val8)GLP-1 improved glucose tolerance, reduced the glycemic excursion after feeding, increased the plasma insulin response to glucose and feeding, and improved insulin sensitivity. These effects were consistently greater with (Val8)GLP-1 than with native GLP-1, and both peptides retained or increased their acute efficacy compared with initial administration. (Val8)GLP-1 treatment increased average islet area 1.2-fold without changing the number of islets, resulting in an increased number of larger islets. These data demonstrate that (Val8)GLP-1 is more effective and longer acting than native GLP-1 in obese-diabetic ob/ob mice.     

Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever,cold sensitivity,sensorineural deafness,and AA amyloidosis

Objective

Familial cold urticaria (FCU) and Muckle‐Wells syndrome (MWS) are dominantly inherited autoinflammatory disorders that cause rashes, fever, arthralgia, and in some subjects, AA amyloidosis, and have been mapped to chromosome 1q44. Sensorineural deafness in MWS, and provocation of symptoms by cold in FCU, are distinctive features. This study was undertaken to characterize the genetic basis of FCU, MWS, and an overlapping disorder in French Canadian, British, and Indian families, respectively.

Methods

Mutations in the candidate gene NALP3, which has also been named CIAS1 and PYPAF1, were sought in the study families, in a British/Spanish patient with apparent sporadic MWS, and in matched population controls. Identified variants were sought in 50 European subjects with uncharacterized, apparently sporadic periodic fever syndromes, 48 subjects with rheumatoid arthritis (RA), and 19 subjects with juvenile idiopathic arthritis (JIA).

Results

Point mutations, encoding putative protein variants R262W and L307P, were present in all affected members of the Indian and French Canadian families, respectively, but not in controls. The R262W variant was also present in the subject with sporadic MWS. The V200M variant was present in all affected members of the British family with MWS, in 2 of the 50 subjects with uncharacterized periodic fevers, and in 1 of 130 Caucasian and 2 of 48 Indian healthy controls. No mutations were identified among the subjects with RA or JIA.

Conclusion

These findings confirm that mutations in the NALP3/CIAS1/PYPAF1 gene are associated with FCU and MWS, and that disease severity and clinical features may differ substantially within and between families. Analysis of this gene will improve classification of patients with inherited or apparently sporadic periodic fever syndromes.