A study finds that people without diabetes with high blood glucose levels have a greater risk of developing dementia.
A recent study found a positive correlation between one's level of blood glucose and his or her risk of developing dementia in the next 6-7 years. (Glucose levels and risk of dementia, 2013. Paul Crane, et al.). This association was found in patients without diabetes, but not those with diabetes. The study was published in the New England Journal of Medicine.
The study utilized 2,067 study participants with an average age of 76. 232 of the patients were diagnosed with dementia. Glycemia measurements were averaged over the course of five years. Dementia was assessed during a follow-up period that lasted a median of 6.8 years. 524 of the patients developed dementia during the follow-up period. Dementia was assessed by all causes including Alzheimer's disease, vascular disease and Lewybody disease.
Different relationships were found in diabetics and non-diabetics. A positive relationship was found across the entire range of blood glucose levels in non-diabetics. This means that an increase in blood glucose would be associated with a higher risk of dementia. Likewise, diabetics demonstrated a positive association between blood glucose levels and risk of developing dementia at above average blood glucose levels. However, at low blood glucose levels, diabetics showed a negative relationship between risk of developing dementia and blood glucose levels. The authors acknowledge that this negative relationship may be driven by three diabetic patients with atypical courses of Type II diabetes. The figures below illustrate these relationships between blood glucose levels and risk of dementia in diabetics and non-diabetics.
Although this study shows a clear, positive relationship between dementia risk and blood glucose levels in non-diabetics, the mechanism has not been determined. Possible mechanisms include acute and chronic hyperglycemia and insulin resistance, and microvascular disease of the central nervous system. Whether actively lowering blood glucose would decrease the risk of dementia has not been determined, but it may be advisable for elderly patients with high levels of blood glucose to partake in dementia prevention strategies such as exercise and maintaining a healthy diet.
A study finds that potential physiological mechanisms that explain why elderly people fail to recover from muscle atrophy are myostatin expression and Pax7+ stem cell proliferation.
Exercise should be a lifelong endeavor. Unfortunately, as we age, the human body's capacity for muscle growth diminishes. A new study has found some potential factors that prevent elderly people from regrowing muscle as fast as their younger counterparts. Understanding why elderly people fail to produce new muscle in at a sufficient rate for regrowth can help the biomedical community develop new therapies for muscle atrophy. The aforementioned study points to satellite stem cells and the muscle growth inhibitor myostatin as the primary physiological links between aging and muscle regrowth (Ageing is associated with diminished muscle re-growth and myogenic precursor cell expansion early after immobility-induced atrophy in human skeletal muscle, 2013. Suetta, et al.).
Because the primary findings of the study are focused on the effects of Pax7+ stem cells and myostatin it is important to have a bit of background in them. Pax7+ stem cells are satellite cells around the skeletal myofibers. A myofiber is multinucleate, which means it has multiple nuclei spanning the length of the cell. When the muscle cell grows, the Pax7+ stem cells are incorporated into the cell. While Pax7+ cells play a role in muscle growth, or hypertrophy, myostatin is a negative regulator of hypertrophy. Myostatin is labeled a growth and differentiation factor, but it opposes muscle growth.
The study utilized 20 healthy male subjects, 11 of which were designated young males (21-30 years of age) and 9 of which were designated older males (61-74 years of age). The study design is as follows. The subjects underwent two weeks of unilateral whole-leg casting using a light-weight whole-leg cast. The subjects then had 4 weeks of retraining for the immobilized leg. The training was supervised and was held three times a week. Muscle biopsies were taken and analyzed before immobilization, after immobilization, 3 days into retraining and at the conclusion of the 4 week retraining program.
The figure below shows how pax7+ stem cells were counted. Pax7 is a protein expressed in the stem cells that can be identified using antibodies, a process called immunohistochemistry. The pax7+ cells were then associated with Type I (slow twitch) and Type II (fast twitch) muscle fibers.
Age effects were seen chiefly with the type II myofibers. Type II myofibers are fast-twitch muscle fibers and rely primarily on glycolytic energy. Thus, type II fibers are used for anaerobic activity like sprinting or lifting weights. No age effects were observed in the Type I fibers, which are slow-twitch, oxidative and used for aerobic activities like standing, walking and endurance running. The Type II myofiber area was found to be significantly larger in the young males after retraining. No age effect in myofiber area following retraining was found in the Type I myofibers. A similar result was observed with Pax7+ stem cells per muscle fiber. The age related effect in Pax7+ stem cells per myofiber following retraining was only observed in the Type II fibers. Young males were observed at 3 days and 4 weeks into the retraining program to have significantly higher amounts of Pax7+ stem cells per type II fiber than the older males. However, the young males did significantly increase Pax7+ cells per Type I fiber over the course of the retraining program, just not significantly compared to the older males. The figure below highlights the changes in Pax7+ cells per type I myofiber and type II myofiber over the course of the study.
A number of growth factors that play a role in regulating muscle growth were looked at. These included insulin-like growth factor-1, MyoD1, hepatocyte growth factor, fibroblast growth factors, cyclin inhibitors and myostatin. Growth factor expression was measured and quantified using mRNA levels in the muscle biopsies. Only myostatin showed a significant age effect. Three days into the retraining program, the young males showed significantly depressed levels of myostatin relative to their older counterparts. Recall that myostatin is a negative regulator of muscle growth. Therefore, having a reduced amount of myostatin would facilitate muscle regeneration. As an aside, myostatin inhibitors have been looked at for their potential use as a therapy for muscle dystrophy and an illegal mechanism for increasing muscle mass in competitive athletes.
In summary, it appears that there are age-related physiological differences in recovering from muscle atrophy. During retraining from muscle immobilization, young males showed an enlargement in Type II muscle fiber area, an increase in Pax7+ stem cell localization with Type II myofibers and down regulation in myostatin expression.