Volume 3 - 2009

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Volume 3 - 2009

Topics

Cardiovascular
Nutrition
Aging
Diabetes
Exercise and Physiology
Hormones
Cognitive
Miscellaneous
Letters to the Editor
Commentaries
Reviews

Cardiovascular

Headline—Family Testing of Congenital Heart Disease (CHD) Does Not Mean Family Member May Have CHD

Recurrence of congenital heart defects in families

Abbreviated Abstract: BACKGROUND: Knowledge of the familial contribution to congenital heart diseases (CHD) on an individual and population level is sparse. We estimated an individual's risk of CHD given a family history of CHD, as well as the contribution of CHD family history to the total number of CHD cases in the population. CONCLUSIONS: Specific CHDs showed highly variable but strong familial clustering in first-degree relatives, ranging from 3-fold to 80-fold compared with the population prevalence, whereas the crossover risks between dissimilar cases of CHD were weaker. Family history of any CHD among first-degree relatives accounted for a small proportion of CHD cases in the population.

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Øyen Poulsen G, Boyd HA, Wohlfahrt J, Jensen PK, Melbye M. Circulation. 2009 Jul 28;120(4):295-301.

Headline—High Blood Pressure Creates Greater Risk of Cognition in Men and Women 65 to 74 Years of Age

The effect of age on the association between blood pressure and cognitive function later in life

Abbreviated Abstract: OBJECTIVES: To determine the prospective relationship between blood pressure (BP) and cognitive function across a wide age range. DESIGN: Prospective population-based cohort study. SETTING: The Rotterdam Study and the Leiden 85-plus Study. PARTICIPANTS: Three thousand seventy-eight men and women, initial age 55 to 84 from the Rotterdam Study and 276 men and women, initial age 85, from the Leiden 85-plus Study. CONCLUSION: High BP was associated with greater risk of cognitive impairment in persons younger than 75 but with better cognitive function in older persons. Age-specific guidelines for BP management are needed, because the current directive that "lower is better" may not apply to BP levels in the very old.

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Euser SM, van Bemmel T, Schram MT, Gussekloo J, Hofman A, Westendorp RG, Breteler MM. J Am Geriatr Soc. 2009 Jul;57(7):1232-7.

Headline—Men with Low to Normal Testosterone Levels Have Increased Risk of Stroke and Transient Ischemic Attack

Lower testosterone levels predict incident stroke and transient ischemic attack in older men

Abbreviated Abstract: CONTEXT: Lower circulating testosterone concentrations are associated with metabolic syndrome, type 2 diabetes, carotid intima-media thickness, and aortic and lower limb arterial disease in men. However, it is unclear whether lower testosterone levels predict major cardiovascular events. OBJECTIVE: We examined whether lower serum testosterone was an independently significant risk factor for symptomatic cerebrovascular events in older men. DESIGN: This was a prospective observational study with median follow-up of 3.5 yr. SETTING: Community-dwelling, stroke-free older men were studied. PARTICIPANTS: A total of 3443 men at least 70 yr of age participated in the study. CONCLUSIONS: In older men, lower total testosterone levels predict increased incidence of stroke or TIA after adjusting for conventional risk factors for cardiovascular disease. Men with low-normal testosterone levels had increased risk. Further studies are warranted to determine whether interventions that raise circulating testosterone levels might prevent cerebrovascular disease in men.

Click here for full abstract. You must be a subscriber of Journal of Clinical Endocrinology and Metabolism to access full article. Click here to sign in or subscribe.

Yeap BB, Hyde Z, Almeida OP, Norman PE, Chubb SA, Jamrozik K, Flicker L, Hankey GJ. J Clin Endocrinol Metab. 2009 Jul;94(7):2353-9.

Headline—Six Out of 10 Deaths From Cardiovascular Disease Can be Prevented

Risk factors for cardiovascular disease in women

Abbreviated Abstract: Management of women's health seldom includes cardiovascular disease (CVD) prevention in spite of CVD being the most common cause of death in females being even more common than cancer, HIV/AIDS, malaria and tuberculosis combined. According to the World Heart Federation, CVD is indisputably the most serious, neglected health problem for women in both the developing and the developed worlds. A possible reason may be that CVD has traditionally been perceived as a 'man's illness'. Since 6 out of 10 deaths from CVD can be prevented, it is of utmost importance that there is more general awareness about CVD in women. The most important factors for developing CVD are dyslipidaemia, hypertension, smoking, stress, diabetes, obesity (especially abdominal fat distribution), physical inactivity, poor eating habits and possibly excessive alcohol intake. Some unique risk factors for CVD exist in women; of which older age at presentation is a major one as they are more likely to suffer from co-morbidities such as diabetes and hypertension.

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Schenck-Gustafsson K. Maturitas. 2009 Jul 20;63(3):186-90.

Nutrition

Headline—Vitamin D, Calcium and Physical Activity are Critical for Double-Diseased Burdened Individuals

Osteoporosis and congestive heart failure (CHF) in the elderly patient: double disease burden

Abbreviated Abstract: The present study aimed to evaluate the association between osteoporosis and CHF in elderly patients and to assess the effect of physical performance, vitamin D levels, inflammatory markers on this association. One hundred and twenty-six consecutive patients aged 65 years and above, with moderate to severe CHF who presented to our institution for CHF management and 54 age- and sex-matched controls were screened for osteoporosis. Bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry (DXA) were performed at the lumbar spine (LS) and femoral neck (FN). Physical performance assessment included grip strength, 6-min walk, "Get up and Go Test", activities of daily living (ADL) and frailty assessment. Biochemical assessment included measurement of levels of serum calcium, phosphorus, 1, 25-dihyroxycholecalciferol=1, 25(OH)(2)D (vitamin D(3)) and tumor necrosis factor-alpha (TNF-alpha). A significant association was found between EF and frailty score, p<0.001. The results suggest that there is an association between HF and lower BMD. The increased bone loss in conjunction with CHF is likely to increase fracture risk. Thus, strategies for optimal treatment of CHF and for optimizing vitamin D(3), calcium and physical activity to improve quality of life (QoL) in these patients who have double disease burden are critical in these individuals.

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Abou-Raya S, Abou-Raya A. Arch Gerontol Geriatr. 2009 Sep-Oct;49(2):250-4.

Headline—Popular Choices Mandates To Make Food Content Healthier

Cholesterol control beyond the clinic: New York City's trans fat restriction

Abbreviated Abstract: Decades after key modifiable risk factors were identified, cardiovascular disease remains the leading cause of preventable death, and only one quarter of persons with high cholesterol levels have attained recommended levels of control. Cholesterol control efforts have focused on consumer education and medical treatment. A powerful, complementary approach is to change the makeup of food in restaurants. Preliminary analyses suggest that replacement of artificial trans fat has resulted in products with more healthful fatty acid profiles. For example, in major restaurant chains, total saturated fat plus trans fat in French fries decreased by more than 50%. At 2 years, dozens of national chains had removed artificial trans fat, and 13 jurisdictions, including California, had adopted similar laws. Public health efforts that change food content to make default choices healthier enable consumers to more successfully meet dietary recommendations and reduce their cardiovascular risk.

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Angell SY, Silver LD, Goldstein GP, Johnson CM, Deitcher DR, Frieden TR, Bassett MT. Ann Intern Med. 2009 Jul 21;151(2):129-34.

Headline—Calorie Restriction Increases Overall Physical Activity

Influence of calorie restriction on measures of age-related cognitive decline: role of increased physical activity

Abbreviated Abstract: Controversy exists as to whether lifelong 40% calorie restriction (CR) enhances, has no effect on, or disrupts cognitive function during aging. Here, we report the effects of CR versus ad-lib feeding on cognitive function in male Brown Norway x Fisher344 rats across a range of ages (8-38 months), using two tasks that are differentially sensitive to age-related cognitive decline: object recognition and Morris water maze (MWM). All ages performed equally in object recognition, whereas, as a group, CR rats were impaired. In contrast, there was an age-related impairment in the MWM that was attenuated by CR as measured by time in proximity with and latency to reach the platform. Distance to the platform, a more sensitive measure, was not affected by CR. Finally, CR resulted in an overall increase in physical activity, one of several behavioral confounders to consider in the interpretation of cognitive outcomes in both tasks.

Click here for full abstract. You must be a subscriber of Journals of Gerontology to access full article. Click here to sign in or subscribe.

Carter CS, Leeuwenburgh C, Daniels M, Foster TC. J Gerontol A Biol Sci Med Sci. 2009 Aug;64(8):850-9.

Headline—Fish Oil May Alter the Immune Response to Influenza Infection

Fish oil-fed mice have impaired resistance to influenza infection

Abbreviated Abstract: Dietary fish oils, rich in (n-3) PUFA, including eicosapentaenoic acid and docosahexaenoic acid, have been shown to have anti-inflammatory properties. Although the anti-inflammatory properties of fish oil may be beneficial during a chronic inflammatory illness, the same anti-inflammatory properties can suppress the inflammatory responses necessary to combat acute viral infection. Given that (n-3) fatty acid-rich fish oil supplementation is on the rise and with the increasing threat of an influenza pandemic, we tested the effect of fish oil feeding for 2 wk on the immune response to influenza virus infection. Lungs of infected fish oil-fed mice had significantly fewer CD8+ T cells and decreased mRNA expression of macrophage inflammatory protein-1-alpha, tumor necrosis factor-alpha, and interleukin-6. These results suggest that the anti-inflammatory properties of fish oil feeding can alter the immune response to influenza infection, resulting in increased morbidity and mortality.

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Schwerbrock NM, Karlsson EA, Shi Q, Sheridan PA, Beck MA. J Nutr. 2009 Aug;139(8):1588-94.

Headline—High-dose Oral Vitamin D3 Supplementation in the Elderly Rapidly and Safely Increases 250 Hydroxyvitamin D Level

High-dose oral vitamin D3 supplementation in the elderly

Abbreviated Abstract: SUMMARY: Daily dosing with vitamin D often fails to achieve optimal outcomes, and it is uncertain what the target level of 25-hydroxyvitamin D should be. This study found that large loading doses of vitamin D(3) rapidly and safely normalize 25OHD levels, and that monthly dosing is similarly effective after 3-5 months. With baseline 25OHD > 50 nmol/L, vitamin D supplementation does not reduce PTH levels. INTRODUCTION: There is concern that vitamin D supplementation doses are frequently inadequate, and that compliance with daily medication is likely to be suboptimal. METHODS: This randomized double-blind trial compares responses to three high-dose vitamin D(3) regimens and estimates optimal 25-hydroxyvitamin D (25OHD) levels, from changes in parathyroid hormone (PTH), and procollagen type I amino-terminal propeptide (P1NP) in relation to baseline 25OHD. Sixty-three elderly participants were randomized to three regimens of vitamin D supplementation: a 500,000-IU loading dose; the loading dose plus 50,000 IU/month; or 50,000 IU/month. CONCLUSIONS: Large loading doses of vitamin D(3) rapidly and safely normalize 25OHD levels in the frail elderly. Monthly dosing is similarly effective and safe, but takes 3-5 months for plateau 25OHD levels to be reached.

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Bacon CJ, Gamble GD, Horne AM, Scott MA, Reid IR. Osteoporos Int. 2009 Aug;20(8):1407-15.

Aging

Headline—Telomere Length-An Informative Biomarker of Healthy Aging

Association between telomere length, specific causes of death, and years of healthy life in health, aging, and body composition, a population-based cohort study

Abbreviated Abstract: Although telomere length (TL) is known to play a critical role in cellular senescence, the relationship of TL to aging and longevity in humans is not well understood. In a large biracial population-based cohort, we tested the hypotheses that elderly persons with shorter TL in peripheral white blood cells have poorer survival, shorter life span, and fewer years of healthy life (YHL). Associations were evaluated using Cox proportional hazard models and linear regression analyses where appropriate. TL (in kilo base pairs) was not associated with overall survival (hazard ratio 1.0; 95% confidence interval 0.9-1.1) or death from any specific underlying cause including infectious diseases, cancer, or cardiac and cerebrovascular diseases. TL, however, was positively associated with more YHL (beta = 0.08 +/- 0.04, p = .03). Findings suggest that TL may not be a strong biomarker of survival in older individuals, but it may be an informative biomarker of healthy aging.

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Njajou OT, Hsueh WC, Blackburn EH, Newman AB, Wu SH, Li R, Simonsick EM, Harris TM, Cummings SR, Cawthon RM; Health ABC study. J Gerontol A Biol Sci Med Sci. 2009 Aug;64(8):860-4.

Headline—Women Are Biologically Stronger Than Men

Biomarkers by gender

Abbreviated Abstract: Regressions were determined for age-related human biological functions containing information for both genders. Their intercept T(0) on the age axis (x) was used as a measure of the aging rate. The peak of the frequency distribution of T(0) was consistent with earlier estimates. The frequency distribution of the ratio R of T(0)(women)/T(0)(men) peaked at unity. However, when the T(0)-values were divided into two groups, namely those relating to functions involving musculature vs. the rest, respectively, the ratio of R for musculature was <1 and that for the latter significantly >1. This suggests that men are the stronger gender when musculature is involved, but, more broadly, women are "biologically stronger".

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Weale R. Arch Gerontol Geriatr. 2009 Sep-Oct;49(2):208-11.

Diabetes

Headline—Type 2 Diabetes and Other Cardiovascular Disease Risk Were Not Increased Due to Menopause

Type 2 diabetes mellitus and other cardiovascular risk factors are no more common during menopause: longitudinal study

Abbreviated Abstract: OBJECTIVE: The aim of this study was to undertake a prospective study of the changes in certain risk factors for cardiovascular disease occurring during menopause. METHODS: A longitudinal cohort study of 475 women was followed up for 6 years (Pizarra Study). The final menstrual period was defined after at least 6 months of amenorrhea. The women were classified into three groups: group 1, no menopause at either the first or second study; group 2, no menopause at the first study but menopause at the second study (6 y later); and group 3, menopause at the first study (and also at the second). The following are the main outcome measures used: age; body mass index; waist circumference; waist-to-hip ratio; skinfold thickness; arm circumference; intake of macronutrients (quantitative questionnaire); systolic and diastolic blood pressures; cholesterol, triglycerides; high-density lipoprotein cholesterol; uric acid; homeostasis model assessment of insulin resistance; and the prevalence of obesity, hypertension, type 2 diabetes mellitus, impaired glucose tolerance, and impaired fasting glucose. CONCLUSIONS: Menopause is a biological condition of the human species, for which has recently received attempts at medicalization that were not always justified. If menopause is not accompanied by any other cardiovascular risk factor independently of age, the stigma of menopause being considered a risk factor should cease. Although the results have the strength of a prospective study, the sample size forced us to consider these findings as preliminary.

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Soriguer F, Morcillo S, Hernando V, Valdés S, Ruiz de Adana MS, Olveira G, Fuentes EG, González I, Tapia MJ, Esteva I, Rojo-Martínez G. Menopause. 2009 Jul-Aug;16(4):817-21.

Headline—Frequency of Serious Complications in Patients with Type 1 Diabetes Decrease Due to Treatment

Modern-day clinical course of type 1 diabetes mellitus after 30 years' duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983-2005)

Abbreviated Abstract: BACKGROUND: Clinical treatment goals of type 1 diabetes mellitus (T1DM) have changed since the Diabetes Control and Complications Trial (DCCT) demonstrated reduced long-term complications with intensive diabetes therapy. There have been few longitudinal studies to describe the clinical course of T1DM in the age of intensive therapy. Our objective was to describe the current-day clinical course of T1DM. RESULTS: After 30 years of diabetes, the cumulative incidences of proliferative retinopathy, nephropathy, and cardiovascular disease were 50%, 25%, and 14%, respectively, in the DCCT conventional treatment group, and 47%, 17%, and 14%, respectively, in the Epidemiology of Diabetes Complications (EDC) cohort. The DCCT intensive therapy group had substantially lower cumulative incidences (21%, 9%, and 9%) and fewer than 1% became blind, required kidney replacement, or had an amputation because of diabetes during that time. CONCLUSION: The frequencies of serious complications in patients with T1DM, especially when treated intensively, are lower than that reported historically.

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Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group, Nathan DM, Zinman B, Cleary PA, Backlund JY, Genuth S, Miller R, Orchard TJ. Arch Intern Med. 2009 Jul 27;169(14):1307-16.

Headline—Potential Interventions in Type 2 Diabetes for Significant Public Health Impact

Type 2 diabetes prevention in the real world: three-year results of the GOAL lifestyle implementation trial

Abbreviated Abstract: OBJECTIVE: We study the effectiveness of the GOAL Lifestyle Implementation Trial at the 36-month follow-up. RESEARCH DESIGN AND METHODS Participants (n = 352, type 2 diabetes risk score FINDRISC = 16.2 +/- 3.3, BMI 32.6 +/- 5.0 kg/m(2)) received six lifestyle counseling sessions over 8 months. Measurements were at baseline, 12 months (88.6%), and 36 months (77.0%). RESULTS: Statistically significant risk reduction at 12 months was maintained at 36 months in weight (-1.0 +/- 5.6 kg), BMI (-0.5 +/- 2.1 kg/m(2)), and serum total cholesterol (-0.4 +/- 1.1 mmol/l). CONCLUSIONS: Maintenance of risk reduction in this "real world" trial proves the intervention's potential for significant public health impact.

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Absetz P, Oldenburg B, Hankonen N, Valve R, Heinonen H, Nissinen A, Fogelholm M, Talja M, Uutela A. Diabetes Care. 2009 Aug;32(8):1418-20.

Headline—Lifestyle Intervention May Be Cost-Effective for Diabetes Patients

Cost-effectiveness of lifestyle modification in diabetic patients

Abbreviated Abstract: OBJECTIVE: To explore the potential long-term health and economic consequences of lifestyle interventions for diabetic patients. RESEARCH DESIGN AND METHODS: A literature search was performed to identify interventions for diabetic patients in which lifestyle issues were addressed. We selected recent (2003-2008), randomized controlled trials with a minimum follow-up of 12 months. The long-term outcomes for these interventions, if implemented in the Dutch diabetic population, were simulated with a computer-based model. Costs and effects were discounted at, respectively, 4 and 1.5% annually. A lifelong time horizon was applied. Probabilistic sensitivity analyses were performed, taking account of variability in intervention costs and (long-term) treatment effects. CONCLUSIONS: Implementation of lifestyle interventions would probably yield important health benefits at reasonable costs. However, essential evidence for long-term maintenance of health benefits was limited. Future research should be focused on long-term effectiveness and multiple treatment strategies should be compared to determine incremental costs and benefits of one over the other.

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Jacobs-van der Bruggen MA, van Baal PH, Hoogenveen RT, Feenstra TL, Briggs AH, Lawson K, Feskens EJ, Baan CA. Diabetes Care. 2009 Aug;32(8):1453-8.

Headline—Higher Noncalcified Plaque in Patients with Type 2 Diabetes vs. Type 1 Diabetes

Differences in atherosclerotic plaque burden and morphology between type 1 and 2 diabetes as assessed by multislice computed tomography

Abbreviated Abstract: OBJECTIVE: It is unclear whether the coronary atherosclerotic plaque burden is similar in patients with type 1 and type 2 diabetes. By using multislice computed tomography (MSCT), the presence, degree, and morphology of coronary artery disease (CAD) in patients with type 1 and type 2 diabetes were compared. RESEARCH DESIGN AND METHODS: Prospectively, coronary artery calcium (CAC) scoring and MSCT coronary angiography were performed in 135 symptomatic patients (65 patients with type 1 diabetes and 70 patients with type 2 diabetes). The presence and extent of coronary atherosclerosis as well as plaque phenotype were assessed and compared between groups. CONCLUSIONS: Although CAC scores and the prevalence of coronary atherosclerosis were similar between patients with type 1 and type 2 diabetes, CAD was more extensive in the latter. Also, a relatively higher proportion of noncalcified plaques was observed in patients with type 2 diabetes. These observations may be valuable in the development of targeted management strategies adapted to diabetes type.

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Djaberi R, Schuijf JD, Boersma E, Kroft LJ, Pereira AM, Romijn JA, Scholte AJ, Jukema JW, Bax JJ. Diabetes Care. 2009 Aug;32(8):1507-12.

Headline—Reduction of Blood Glucose and Insulin are Independent to Anti-Inflammatory Effect in Type 2 Diabetes

Independent anti-inflammatory effect of insulin in newly diagnosed type 2 diabetes

Abbreviated Abstract: BACKGROUND: Although insulin has been reported to have an anti-inflammatory effect, whether this effect is independent of its property to reduce blood glucose with insulin treatment in type 2 diabetes has not been investigated in detail. The purpose of this study was to evaluate the independent anti-inflammatory effect of insulin in patients with newly diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS: An 8-week, randomized, parallel-group study that enrolled 90 patients with newly diagnosed type 2 diabetes, who were randomly assigned to receive either insulin or metformin, was carried out. The doses of insulin and metformin were titrated according to fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) during the 4 weeks; the target of FPG was 126 mg/dL and that of PPG was 160 mg/dL. The blood glucose levels were kept stabilized till the end of the study. The serum concentrations of high-sensitive C-reactive protein (hsCRP) and interleukin (IL)-6 were measured before starting the study and 4 and 8 weeks after initiation of insulin or metformin therapy. CONCLUSIONS: Our data suggest that insulin has an anti-inflammatory effect that is independent of the reduction it causes in blood glucose.

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Mao XM, Liu H, Tao XJ, Yin GP, Li Q, Wang SK. Diabetes Metab Res Rev. 2009 Jul;25(5):435-41.

Headline—Short-term Aerobics Positively Impacts Arterial Thickness Caused by Type 2 Diabetes and/or Hypertension

Short-term aerobic exercise reduces arterial stiffness in older adults with type 2 diabetes, hypertension, and hypercholesterolemia

Abbreviated Abstract: OBJECTIVE: The relationship between increased arterial stiffness and cardiovascular mortality is well established in type 2 diabetes. We examined whether aerobic exercise could reduce arterial stiffness in older adults with type 2 diabetes complicated by comorbid hypertension and hyperlipidemia. RESEARCH DESIGN AND METHODS: A total of 36 older adults (mean age 71.4 +/- 0.7 years) with diet-controlled or oral hypoglycemic-controlled type 2 diabetes, hypertension, and hypercholesterolemia were recruited. Subjects were randomly assigned to one of two groups: an aerobic group (3 months vigorous aerobic exercise) and a nonaerobic group (no aerobic exercise). Exercise sessions were supervised by a certified exercise trainer three times per week, and a combination of cycle ergometers and treadmills was used. Arterial stiffness was measured using the Complior device. CONCLUSIONS: Our findings indicate that a relatively short aerobic exercise intervention in older adults can reduce multifactorial arterial stiffness (type 2 diabetes, aging, hypertension, and hypercholesterolemia).

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Madden KM, Lockhart C, Cuff D, Potter TF, Meneilly GS. Diabetes Care. 2009 Aug;32(8):1531-5.

Headline—Adult Offspring of Women with Diet-Treated Type 1 Diabetes are at Risk for Metabolic Syndrome

Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes

Abbreviated Abstract: CONTEXT: In animal studies, exposure to intrauterine hyperglycemia increases the risk of cardiovascular disease through only partly understood epigenetic mechanisms. Human long-term follow-up studies on the same topic are few. OBJECTIVE: The aim was to study the risk of overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus (GDM) or type 1 diabetes, and additionally to study associations between estimates of maternal hyperglycemia and outcome in the offspring. DESIGN AND SETTING: We conducted a follow-up study of 1066 primarily Caucasian women aged 18-27 yr in the Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark. PARTICIPANTS: Offspring of women with diet-treated GDM (n = 168) and an unexposed reference group (n = 141) participated, as well as offspring of women with type 1 diabetes (n = 160) and offspring from the background population representing an unexposed reference group (n = 128). The follow-up rate was 56% (597 of 1066). CONCLUSIONS: Adult offspring of women with diet-treated GDM or type 1 diabetes are risk groups for overweight and the metabolic syndrome. Intrauterine hyperglycemia may in addition to genetics and other factors contribute to the pathogenesis of overweight and the metabolic syndrome.

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Clausen TD, Mathiesen ER, Hansen T, Pedersen O, Jensen DM, Lauenborg J, Schmidt L, Damm P. J Clin Endocrinol Metab. 2009 Jul;94(7):2464-70.

Exercise and Physiology

Headline—Tai Chi Improves Motor Ability in the Elderly

Is Tai Chi Chuan effective in improving lower limb response time to prevent backward falls in the elderly?

Abbreviated Abstract: To evaluate the training effect of Tai Chi Chuan (TCC) in postural control and backward fall prevention in the elderly, balance assessment and visually guided lower limb response time were analyzed in a case-control study conducted in a community setting. Thirty-one elderly subjects (mean age: 68.2 +/- 6.8 years) participated in the TCC group, 30 community-dwelling elderly subjects with matched age and body composition served as the elderly control group, with 13 young adults (mean age: 27.5 +/- 3.8 years) serving as young controls. The TCC group had practiced TCC regularly five times per week, for over 30 min per day for at least 4 years. Lower limb response time were measured using a computerized dance machine that we developed, which contains two blocks during testing: single and dual feet. The TCC group had better dual feet response than the elderly controls in the forward-backward, forward-right and forward-left directions. Practicing TCC may improve motor responses and postural control in the elderly, particularly in more challenging situations. Subjects showed better postural responses to unexpected perturbation in the forward-backward and forward-sideways direction than sideways or backward-sideways directions, which may have clinical relevance.

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Wong AM, Pei YC, Lan C, Huang SC, Lin YC, Chou SW. Age (Dordr). 2009 Jun;31(2):163-70.

Headline—A 30-day Period of Interruption of Physical Activity Did Not Alter the Values of Physical Capacity of Active Women

The effects of periodic interruptions of physical activities on the physical capacities of adult active women

Abbreviated Abstract: Physical activity programs adapted to the elderly have been proposed with the purpose of minimizing the alterations provoked by aging. These programs usually present break periods of more than 30 days, at least once a year. The aim of this study was to verify if 30-day interruptions cause alterations in the acquisition of physical capacities for senescent women. 125 senescent women completed a physical activity program consisting of stretching, aerobic resistance, strength, power and resistance exercises; coordination, agility and flexibility activities; respiratory and relaxation exercises during almost 2 years. The main outcome measures were manual pressing strength, flexibility, dynamic balance and physical conditioning (VO2max). During the program, the dynamic balance showed significant difference (p<0.0001), but there was no significant difference in the interruption periods. It was possible to observe that 30 days of interruption of physical activities in both studied periods were not enough to significantly alter the values of physical capacities of senescent active women.

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Greve P, Wanderley Fda S, Rebelatto JR. Arch Gerontol Geriatr. 2009 Sep-Oct;49(2):268-71.

Headline—Swim Training in Mice Retarded the Development of Ehrlich Tumors

Swim training suppresses tumor growth in mice

Abbreviated Abstract: The present study was designed to determine the effects of physical training on the development of cancer induced by the injection of Ehrlich tumor cells in mice. Male Swiss mice were subjected to a swim training protocol (5 days/wk for 6 wk, 1 h at 50% of maximal capacity-trained groups) or remained sedentary in their cages (sedentary groups). Heart and solid tumor weights were recorded, and tumor volumes were calculated. Portions of the tumors were used for the evaluation of macrophages and neutrophil accumulation or fixed in neutral 10% buffered formalin for histological analysis. The tumor volume and weight were, respectively, approximately 270% and 280% greater in sedentary mice than in trained mice. Macrophage infiltration in the tumor tissue was significantly lower in trained mice (0.65 +/- 0.16 vs. 1.78 +/- 0.43 macrophages x 10(3) in the sedentary group). Moreover, neutrophil accumulation in tumors was slightly reduced after exercise training, and the amount of tumor cells was reduced in trained mice. Exercise capacity was substantially increased in trained mice, as determined by a 440% increase in the exercise time at 50% of maximal capacity. In summary, swim training retarded the development of Ehrlich tumors in mice, accompanied by a reduction in macrophage infiltration and neutrophil accumulation. These findings provide conceptual support for clinical observations that controlled physical activities may be a therapeutically important approach to preventing cancer progression and may improve the outcome of cancer treatment.

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Almeida PW, Gomes-Filho A, Ferreira AJ, Rodrigues CE, Dias-Peixoto MF, Russo RC, Teixeira MM, Cassali GD, Ferreira E, Santos IC, Garcia AM, Silami-Garcia E, Wisløff U, Pussieldi GA. J Appl Physiol. 2009 Jul;107(1):261-5.

Headline—Exercise in a Warm Environment Mitigates the Post-Exercise Fall in Cardiac Output

Fluid replacement and heat stress during exercise alter post-exercise cardiac haemodynamics in endurance exercise-trained men

Abbreviated Abstract: It has been reported that endurance exercise-trained men have decreases in cardiac output with no change in systemic vascular conductance during post-exercise hypotension, which differs from sedentary and normally active populations. As inadequate hydration may explain these differences, we tested the hypothesis that fluid replacement prevents this post-exercise fall in cardiac output, and further, exercise in a warm environment would cause greater decreases in cardiac output. We studied 14 trained men (VO2,peak 4.66 +/- 0.62 l min(-1)) before and to 90 min after cycling at 60% VO2,peak for 60 min under three conditions: Control (no water was consumed during exercise in a thermoneutral environment), Fluid (water was consumed to match sweat loss during exercise in a thermoneutral environment) and Warm (no water was consumed during exercise in a warm environment). Arterial pressure and cardiac output were measured pre- and post-exercise in a thermoneutral environment. The fall in mean arterial pressure following exercise was not different between conditions (P = 0.453). Higher post-exercise cardiac output (Delta 0.41 +/- 0.17 l min(-1); P = 0.027), systemic vascular conductance (Delta 6.0 +/- 2.2 ml min(-1) mmHg(-1); P = 0.001) and stroke volume (Delta 9.1 +/- 2.1 ml beat(-1); P < 0.001) were seen in Fluid compared to Control, but there was no difference between Fluid and Warm (all P > 0.05). These data suggest that fluid replacement mitigates the post-exercise decrease in cardiac output in endurance-exercise trained men. Surprisingly, exercise in a warm environment also mitigates the post-exercise fall in cardiac output.

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Lynn BM, Minson CT, Halliwill JR. J Physiol. 2009 Jul 15;587(Pt 14):3605-17.

Headline—A Year Long Exercise Intervention Decreases C-Reactive Protein Among Obese Post Menopausal Women

A yearlong exercise intervention decreases CRP among obese postmenopausal women

Abbreviated Abstract: PURPOSE: To investigate the effect of a yearlong moderate-intensity aerobic exercise intervention on C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) among overweight or obese postmenopausal women. METHODS: In a randomized controlled trial, 115 postmenopausal, overweight or obese, sedentary women, aged 50-75 yr were randomized to an aerobic exercise intervention of moderate-intensity (60%-75% observed maximal HR), for > or = 45 min x d(-1), 5 d x wk (n = 53), or to a 1-d x wk(-1) stretching control (n = 62), on an intent-to-treat basis. CRP, SAA, and IL-6 were measured at baseline, at 3 months, and at 12 months. CONCLUSIONS: A moderate-intensity exercise intervention reduced CRP for 12 months among women who were obese at baseline. These findings support the role of exercise in modulating inflammatory processes that are related to increased risk of chronic disease among obese women.

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Campbell PT, Campbell KL, Wener MH, Wood BL, Potter JD, McTiernan A, Ulrich CM. Med Sci Sports Exerc. 2009 Aug; 41(8):1533-9.

Headline—The Expenditure of Physical Activity Energy Increased During Extended Exercise

Effects of exercise training amount on physical activity energy expenditure

Abbreviated Abstract: INTRODUCTION: We examined the effects of three exercise training interventions on total physical activity energy expenditure (PAEE) or nonexercise PAEE in a randomized controlled trial where sedentary, overweight, and obese men and women were assigned to inactive control, low-amount/moderate-intensity, low-amount/vigorous-intensity, or high-amount/vigorous-intensity aerobic exercise. METHODS: To measure PAEE, triaxial RT3 accelerometers were worn by subjects for 7 d at the beginning and end of an 8-month exercise intervention. In total, 50 subjects (control, n = 8; two low-amount groups, n = 28; high-amount group, n = 14) had usable PAEE data collected at both time points. RESULTS: At baseline, subjects had an average age of 53.2 yr, had a body mass index of 29.7 kg x m(-2), and a relative peak VO2 of 28.7 mL x kg(-1) x min(-1). There were no significant differences between groups at baseline. After the intervention, average change in total PAEE was 8.4 +/- 20.9 kJ x h(-1) for controls, 58.6 +/- 20.9 kJ x h(-1) for the two low-amount groups, and 138.1 +/- 33.5 kJ x h(-1) for the high-amount group (means +/- SE). The high-amount group experienced a significantly greater increase in total PAEE compared with the controls (P = 0.02). As expected, total PAEE increased with increasing exercise volume. Average change in nonexercise PAEE was 8.4 +/- 20.9 kJ x h(-1) for control, 25.1 +/- 20.9 kJ x h(-1) for the low-amount groups combined, and 62.8 +/- 29.3 kJ x h(-1) for the high-amount group. There was no statistically significant difference in change of nonexercise PAEE among groups. CONCLUSIONS: We conclude that in middle-aged overweight or obese subjects participating in an extended exercise intervention, total PAEE increased, and there was no compensatory decrease in nonexercise PAEE.

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Hollowell RP, Willis LH, Slentz CA, Topping JD, Bhakpar M, Kraus WE. Med Sci Sports Exerc. 2009 Aug;41(8):1640-4.

Headline—Effects of Lean and Fat Mass on Bone Mineral Density and Arterial Stiffness in Elderly Men

Effects of lean and fat mass on bone mineral density and arterial stiffness in elderly men

Abbreviated Abstract: SUMMARY: The role of body composition on arterial stiffness and osteoporosis remains unclear, especially in the elderly male population. Our results indicate that elderly men with high lean mass and low fat mass exhibit the best arterial and bone profile with the lowest arterial stiffness and the highest bone mineral density. INTRODUCTION: The aim of this study was to evaluate the influence of fat and lean mass on both arterial stiffness and bone mass density (BMD) in elderly men. METHODS: This study was performed in 169 French males over 60 years old. Aortic stiffness was assessed by carotid/femoral pulse wave velocity (PWV). BMD and body composition were determined with a dual-energy X-ray absorptiometry device in the lumbar spine L1-L4, femoral neck, and total body. CONCLUSIONS: In males from a general population over 60 years of age, bone and arterial aging are differently influenced by lean and fat mass. Our results indicate that elderly men with high lean mass and low fat mass exhibit the best arterial and bone profile with the lowest arterial stiffness and the highest BMD.

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Benetos A, Zervoudaki A, Kearney-Schwartz A, Perret-Guillaume C, Pascal-Vigneron V, Lacolley P, Labat C, Weryha G. i>Osteoporos Int. 2009 Aug;20(8):1385-91.

Hormones

Headline—Gabapentin Appears to be Favorable For Hot Flushes

Non-hormonal treatment of hot flushes in breast cancer survivors: gabapentin vs. vitamin E

Abbreviated Abstract: Objectives: To assess the efficacy and the tolerability of gabapentin 900 mg/day compared to vitamin E for the control of vasomotor symptoms in 115 women with breast cancer. The secondary objective was to evaluate the effect of the treatments on the quality of sleep and other aspects of the quality of life. Conclusion: Gabapentin appears to be effective for the treatment of hot flushes with a favorable effect on quality of sleep. Vitamin E has only marginal effect on vasomotor symptoms.

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Biglia N, Sgandurra P, Peano E, Marenco D, Moggio G, Bounous V, Tomasi Cont N, Ponzone R, Sismondi P. Climacteric. 2009 May 2:1-9.

Headline-Testosterone Enhances Cognition Effect in Rats

Chronic administration of androgens with actions at estrogen receptor beta have anti-anxiety and cognitive-enhancing effects in male rats

Abbreviated Abstract: Androgen levels decline with aging. Some androgens may exert anti-anxiety and cognitive-enhancing effects; however, determining which androgens have anxiolytic-like and/or mnemonic effects is of interest given the different mechanisms that may underlie some of their effects. Androsterone, another metabolite of T, does not bind well to ERbeta. To investigate the effects of T metabolites, male rats were subjected to gonadectomy then implanted with silastic capsules of 3alpha-diol, 3beta-diol, androsterone, or oil control. After recovery, the rats were tested in elevated plus maze (EPM), light/dark transition (LD), and Morris water maze (MWM). 3alpha-diol both decreased anxiety-like behavior in the EPM and LD, and increased cognition in MWM, while 3beta-diol improved cognition in MWM, but had no effects on anxiety behavior, compared to vehicle or androsterone. These data suggest that the actions of 3alpha-diol and 3beta-diol at ERbeta may be responsible for some of testosterone's anti-anxiety and cognitive-enhancing effects.

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Osborne DM, Edinger K, Frye CA. Age (Dordr). 2009 Sep;31(3):191-8.

Headline—Postmenopausal Women With No Bleeding Do Not Require Automatic Testing

The role of transvaginal ultrasound or endometrial biopsy in the evaluation of the menopausal endometrium

Abbreviated Abstract: All postmenopausal women with vaginal bleeding need endometrial assessment. Disposable suction piston biopsy devices have virtually replaced dilatation and curettage despite little scientific validation. In patients with known carcinoma, false-negative rates with such devices range from 2.5-32.4%. Large prospective studies have shown that an endometrial thickness <or= 4 mm on transvaginal ultrasound in postmenopausal women with bleeding has a risk of malignancy of 1 in 917. Thus, in postmenopausal patients with bleeding, biopsy is not indicted when endometrial thickness is <or= 4 mm. The significance of a thick endometrial echo in nonbleeding postmenopausal women has not been validated and need not require automatic tissue sampling.

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Goldstein SR. Am J Obstet Gynecol. 2009 Jul;201(1):5-11.

Headline-Lower Dosages and Non-Oral Routes Used For HT Since 2002

Changes of menopausal hormone therapy use pattern since 2000: results of the Berlin Spandau Longitudinal Health Study

Abbreviated Abstract: Background: There are virtually no prospective cohort studies in Germany regarding the changes of menopausal hormone therapy (HT) use pattern and factors associated with HT discontinuation after the release of the Women's Health Initiative (WHI) trial results. Conclusions: Substantial declines in HT user prevalence as well as changes in HT use patterns to lower-dose estrogen preparations and non-oral routes of administration are likely to reflect effects of the publication of the WHI results. Consulting a gynecologist appeared to be relevant for a woman's decision to continue HT.

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Du Y, Scheidt-Nave C, Schaffrath Rosario A, Ellert U, Doren M, Knopf H. Climacteric. 2009 May 11:1-12.

Headline—Low Risk Postmenopausal Diabetic Women Should Be Offered Appropriate Hormone Therapy

Diabetes and the menopause

Abbreviated Abstract: Diabetes mellitus is the commonest chronic disease in post-menopausal women and is a predisposing factor for cardiovascular disease, which is the leading cause of death in this cohort in Western societies. Diabetes and the menopause are two independent risk factors for development of cardiovascular disease. Risk factor modification in terms of diabetes appears straightforward; however, correction of estrogen deficiency which hallmarks the menopause appears complex. Our aim is to discuss this question based on the evidence available. Co-morbid diseases are common in post-menopausal diabetics. Hence, it not easy to either conduct or establish clear causal relationships in randomized controlled trials. Consequently, making decisions about treatment becomes difficult. However, it is important adopt strategies to help post-menopausal diabetic women alleviate their menopausal symptoms and to minimize the adverse consequences of their condition. We conclude that the low-risk diabetic post-menopausal women should be offered appropriate hormone replacement therapy, whereas non-oestrogen-based treatments should be the treatment of choice for high-risk women.

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Wedisinghe L, Perera M. Maturitas. 2009 Jul 20;63(3):200-3.

Headline-Salivary Testing Does Not Reduce the Same Results As Serum in Post Menopausal Women

Comparison of salivary versus serum testosterone levels in postmenopausal women receiving transdermal testosterone supplementation versus placebo

Abbreviated Abstract: OBJECTIVE: Clinical assessment of androgen action and its correlation to testosterone levels in women has been challenging. The current gold standard for measuring biologically active testosterone (T) is serum free T by equilibrium dialysis. Alternative methods are desirable due to the cost, complexity, and limited availability of the equilibrium dialysis method. Salivary testing has been proposed as a possible substitute for serum testing. This study compared salivary versus serum measurements of total T (TT), bioavailable T (BT; consisting of free T [FT] and albumin-bound T), and FT from samples collected simultaneously in women who were either receiving transdermal T patch supplementation (300 microg/d) or a placebo patch. METHODS: Naturally and surgically postmenopausal women receiving concomitant hormone therapy were recruited to participate in a 24- to 52-week phase III trial of a 300 microg/day transdermal T patch for the treatment of hypoactive sexual desire disorder. CONCLUSIONS: Although salivary testing of T concentrations is an appealing alternative because it is inexpensive and noninvasive, our results do not support the routine use of salivary T levels in postmenopausal women.

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Flyckt RL, Liu J, Frasure H, Wekselman K, Buch A, Kingsberg SA. Menopause. 2009 Jul-Aug;16(4):680-8.

Headline—Low Dose Conjugated Estrogens Cream Used Daily or Twice a Week Relieves Symptoms in Postmenopausal Women

Efficacy and safety of low-dose regimens of conjugated estrogens cream administered vaginally

Abbreviated Abstract: OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of low-dose conjugated estrogens (CE) cream for treatment of atrophic vaginitis. METHODS: Postmenopausal women (N = 423) with moderate-to-severe vaginal atrophy were randomized to CE cream 0.3 mg or placebo once daily (21 days on/7 days off) or twice weekly for 12 weeks, followed by open-label treatment with CE cream for 40 weeks consistent with their prior regimen. Primary endpoints were changes in vaginal maturation index (VMI; percentage of superficial cells), vaginal pH, and severity of participant-reported most bothersome symptom (vaginal dryness, itching, burning, or dyspareunia) at week 12. Endometrial safety was assessed by transvaginal ultrasound and endometrial biopsy for 52 weeks. CONCLUSIONS: Daily and twice-weekly use of low-dose CE cream was equally effective in relieving symptoms of vulvovaginal atrophy. Both regimens showed endometrial safety and sustained efficacy during 1 year of therapy.

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Bachmann G, Bouchard C, Hoppe D, Ranganath R, Altomare C, Vieweg A, Graepel J, Helzner E. Menopause. 2009 Jul-Aug;16(4):719-27.

Headline—Synthetic Conjugated Estrogens Vaginal Cream Effects in Treating Vaginal Atrophy

Twice-weekly synthetic conjugated estrogens vaginal cream for the treatment of vaginal atrophy

Abbreviated Abstract: OBJECTIVE: The aim of this study was to evaluate low-dose synthetic conjugated estrogens A (SCE-A) cream administered twice weekly for the treatment of moderate to severe vulvovaginal atrophy (VVA) in a symptomatic postmenopausal population. METHODS: In a multicenter, double-blind, randomized, placebo-controlled study, 305 women with symptoms of VVA were treated with either 1 g SCE-A cream (n = 150) or matching placebo (n = 155) for a period of up to 12 weeks. Participants had to have a vaginal pH of greater than 5, less than or equal to 5% superficial cells on a vaginal smear, and at least one of five symptoms of VVA (dryness, soreness, irritation, pain with intercourse, and bleeding after intercourse) that was moderate or severe in intensity. Women had to select one moderate or severe symptom as the most bothersome. CONCLUSIONS: A low dose (1 g = 0.625 mg) of SCE-A vaginal cream administered twice weekly was shown to be effective compared with placebo in treating VVA in postmenopausal women for the three coprimary efficacy measures of maturation index, pH, and severity of the MBS.

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Freedman M, Kaunitz AM, Reape KZ, Hait H, Shu H. Menopause. 2009 Jul-Aug;16(4):735-41.

Cognitive

Headline-Age and Depression Have an Effect on Cognitive Function

Relationships between health status, depression and cognitive functions of institutionalized male veterans

Abbreviated Abstract: The purpose of this study was to explore the relationships among health state, depression, and cognitive functions of institutionalized male veterans. A cross-sectional and correlation research design with a cluster sampling was conducted. A total of 223 veterans who were above 65 years old, with no psychiatric disorders and no organic brain lesions were recruited from two veterans' institutions in Southern Taiwan. The results of this study were as follows: (1) Veterans who were able to read, were married, had good dietary habits, avoided over-oiled and high-fat food to keep healthy, took exercise at least 30 min each time, and had static leisure activities had significant differences in cognitive functions. (2) Cognitive functions were significantly negatively correlated with age and depression, whereas positively correlated with education level, the number of children and perceived health status. (3) Depression, literacy, education level and age were the four predictors of cognitive functions, accounting for 29% of the variance. The findings of this study provide a reference to caregivers and health care professionals for home care, clinical practice and cohort study in the future.

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Chung PJ, Chiou CJ, Chou FH. Arch Gerontol Geriatr. 2009 Sep-Oct;49(2):215-9.

Miscellaneous

Headline—Prevalence of Erectile Dysfunction in Men Screened for Prostate Cancer

Prevalence of erectile dysfunction in men screened for prostate cancer

Abbreviated Abstract: OBJECTIVES: The Sexual Health Inventory for Men (SHIM) is a widely used scale for the screening and diagnosis of erectile dysfunction (ED). Our objective was to incorporate the SHIM into our prostate cancer screening program to estimate the prevalence of ED among men screened for prostate cancer. METHODS: During September 2006, men younger than 75 years of age living in the Washington, DC area were invited to participate in the George Washington University Prostate Cancer Screening Program. The SHIM questionnaire was administered to all participants. Information regarding primary care physician use, phosphodiesterase-5 inhibitor use, serum prostate-specific antigen levels, and digital rectal examination findings was also obtained. Those who registered SHIM scores of 17 or less or who were taking a phosphodiesterase-5 inhibitor were considered to have ED. CONCLUSIONS: The results of our study have shown that ED increases in a nonlinear fashion with age, consistent with the findings of previous reports. Of greater concern, however, given the strong association between ED and cardiovascular disease, was the number of those with ED who lacked a primary care physician.

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Bianco FJ Jr, McHone BR, Wagner K, King A, Burgess J, Patierno S, Jarrett TW. Urology. 2009 Jul;74(1):89-93.

Headline-90% of Women over 60 and Men over 50 May Need Statin Treatment

Is measuring C-reactive protein useful for guiding treatment in women > or = 60 years and men > or = 50 years of age?

Abbreviated Abstract: Using the results of the JUPITER trial, a recent report estimated that up to 11 million older United States (US) adults with C-reactive protein (CRP) levels > or =2 mg/L not currently recommended statins may benefit from treatment. However, the need to measure CRP in making this treatment decision has not been evaluated. Using data from 887 older US men and women (men > or =50 years old, women > or =60 years old) not currently on or recommended statin therapy participating in the National Health and Nutrition Examination Survey 2003 to 2006, we determined the sensitivity, specificity, and positive and negative predictive values of patient characteristics in identifying the presence of CRP > or =2 mg/L. In conclusion, these findings suggest patient characteristics cannot be easily used to identify patients with CRP > or =2 mg/L. Given the demonstrated benefits of statin therapy, cost of measuring CRP, and large percentage of older US adults with high CRP, universal statin therapy for older US adults warrants investigation.

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Muntner P, Mann D, Razzouk L, Klarenbach S, Manns B, Tonelli M, Farkouh ME. Am J Cardiol. 2009 Aug 1; 104(3):354-8.

Headline—Heightening Level of Lipid Peroxidation and High Level of Copper Could Increase Cardiovascular Risk

Effects of oral contraception with ethinylestradiol and drospirenone on oxidative stress in women 18-35 years old

Abbreviated Abstract: BACKGROUND: Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status. STUDY DESIGN: A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ethinylestradiol and 3 mg drospirenone have been compared to a matched control group of 30 noncontraception users (NCU). Blood levels of antioxidants, trace elements and markers of lipid peroxidation were assessed by biochemical methods. A microarray analysis of whole blood mRNA levels of 200 genes involved in OS-dependant pathway was also performed. CONCLUSIONS: The recently introduced combination of ethinylestradiol and drospirenone induced the heightening of lipid peroxidation correlated with high levels of copper, a situation that could be associated with increased cardiovascular risk.

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De Groote D, d'Hauterive SP, Pintiaux A, Balteau B, Gerday C, Claesen J, Foidart JM. Contraception. 2009 Aug;80(2):187-93.

Letters to the Editor

Letter to the Editor of Circulation Research

Inflammation, Adipose Tissue, and T Cells: What Is the "Straight Skinny" on Lean Versus Fat Mice?

Extract: Obesity is associated with chronic inflammation in adipose tissue (AT), as evidenced by increased levels of cytokines/chemokines and accumulation and activation of macrophages and T cells, which are acknowledged as important contributors to insulin resistance in obesity. Recently, using Apoe-/-xCD4dnTGFbR mice, Sultan et al reported that T cell-mediated inflammation does not cause insulin resistance in lean mice. Compared to controls (Apoe-/- mice), lean Apoe-/-xCD4dnTGFbR mice showed increased inflammation in AT (but not specifically in AT), as indicated by increased content of T cells and macrophages, higher levels of tumor necrosis factor- , interferon- , and monocyte chemoattractant protein-1, but a comparable level of interleukin (IL)-6. However, lean Apoe-/-xCD4dnTGFbR mice did not show worsened insulin resistance compared to Apoe-/- mice. Therefore, the authors concluded that T cell-mediated inflammation in AT does not cause insulin resistance in hyperlipidemic mice. We acknowledge Sultan et al for their report on the study of the role of T cell-mediated inflammation in insulin resistance. However, because of the following limitations of this study, we feel that it is too early to make any firm conclusions on the potential role of T cell-mediated AT inflammation in metabolic dysfunctions, particularly with diet-induced obesity, which is commonly accompanied by dyslipidemia.

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Wu H, Ballantyne CM. Circ Res. 2009 Jul 17;105(2):e3-4; author reply e5.

Letters to the Editor of Archives of Internal Medicine

The Difficult Clinical Encounter and Bothersome Patient Behaviors

Extract: I read the survey by An et al and the accompanying editorial by Kroenke with interest. However, the survey design permits addressing only some of the sources of frustration with patients. We performed a survey of neurologists, with the premise that although much is known about patient complaints about physicians, little is known about physician complaints about patients. We chose what we believed to be a more neutral term, i.e., bothersome patient behaviors rather than difficult patients. Participants were presented with 30 patient behaviors (including the 8 in the An et al1 survey) and asked how often they had seen patients with these behaviors in the prior 1 year and how bothersome the behaviors were to them.

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Evans RW. Arch Intern Med. 2009 Jul 27;169(14):1339-40.

The Difficult Clinical Encounter and Bothersome Patient Behaviors-Reply

Extract: We thank Dr Evans for his comment regarding our recent article.1 His survey findings serve to illuminate and further delineate characteristics of patients involved in difficult encounters with their physicians. We agree that a neutral term is best, and selected difficult encounters rather than difficult patients for this reason. Dr Evans' survey complements our work by adding several additional ways in which encounters are perceived as challenging or difficult by physicians. What strikes us is that among his top 5 issues, 4 (no shows, poor compliance, late arrivals, and not knowing medications) could be addressed through novel mechanisms such as patient navigators2-3 and care managers or simple reminder telephone calls.

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An PG, Rabatin JS, Manwell LB, Linzer M, Brown RL, Schwartz MD; MEMO Investigators. Arch Intern Med. 2009 Jul 27;169(14): author reply 1340.

Online Letter in Diabetes Care

Relationship Between Baseline Glycemic Control and Cognitive Function in Individuals With Type 2 Diabetes and Other Cardiovascular Risk Factors: The Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) Trial

Extract: In their recent article, Cukierman-Yaffe et al. (1) performed a cross-sectional study comparing the relationship of A1C and fasting plasma glucose (FPG) levels with performance on four cognitive tests of subjects from the Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. These authors showed that a chronic marker of hyperglycemia, A1C, was associated with significantly lower cognitive performance, whereas FPG did not have any effect. These findings extend those from previous reports regarding the progressive relationship between the degree of chronic hyperglycemia and cognitive dysfunction.

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Abbatecola AM, Paolisso G. Diabetes Care. 2009 Aug;32(8):e102; author reply e103.

Letter to the Editor of Journal of American College of Cardiology

Don't Throw the Baby Out with the Bath Water

Full Letter: Budoff et al. have presented important information from the MESA (Multi-Ethnic Study of Atherosclerosis) trial about the interpretation of coronary artery calcium (CAC) scores. There has been some controversy as to how to interpret what constitutes a high-risk score. Is the age/sex/ethnicity adjusted percentile score or the absolute total score best? To me it seems to depend on what is your question about high risk. In the Budoff et al. article, clearly the authors are interpreting high risk as the risk for a cardiac event in the short term (46 months). However, to the clinician and patient, it is of great importance to determine which individuals are at high risk in the longer term (i.e., decades). The authors cite an example of a 50-year-old Hispanic woman who has a CAC score of 25, which places her in the 95th percentile for age/sex/ethnicity compared with an 83-year-old white man with a CAC of 1,572, which places him in the 72nd percentile for his age/sex/ethnicity. The main point of the article is that although the man has a lower percentile than the woman, he is at much greater risk for a short-term cardiac event. No argument, the greater the atherosclerotic burden the greater the short-term risk. However, I think it is important to recognize that the percentile score has clinically useful information that the absolute score does not. The fact that the 50-year-old woman's score places her in the 95th percentile for age/sex/ethnicity means she will reach the high-risk score of 400 at a much earlier age, probably within 15 years, compared with many of her peers, who had the more likely score of 0 and will take 35 years or longer to achieve a high-risk score. I believe this is very useful information for the physician and the patient and will significantly impact decision-making about diet, lifestyle, and medications. In other words, I think we and our patients are interested in both the short- and long-term risk. If I am a 39-year-old white man with a score of 50, I certainly would want to know that I am likely to have a high-risk score within 10 years. Knowing both short- and long-term risk is useful. The percentile score predicts the long-term risk and tells us how soon, untreated, we will reach a high-risk score. The absolute score represents the atherosclerotic burden currently present and therefore best predicts the short-term risk. However, the Budoff et al. article and the accompanying editorial seem to downplay the importance and value of the percentile score in their enthusiasm to identify the most powerful predictor of short-term risk. The data presented support their enthusiasm, but please don't throw the baby out with the bath water.

Brundage BH.J Am Coll Cardiol. 2009 Aug 4;54(6):574; author reply 574-5.

Commentaries

Vitamin D in diabetes mellitus-a new field of knowledge poised for D-velopment

Extract: This commentary reviews the current state of knowledge regarding the role of vitamin D in the pathogenesis of diabetes mellitus. In type 1 diabetes mellitus or in adult onset latent autoimmune diabetes (LADA), vitamin D exhibits immunomodulatory actions, influencing the activity of lymphocytes and interleukins. In type 2 diabetes mellitus vitamin D appears to act through different mechanisms, affecting insulin secretion and insulin sensitivity through its effects on the beta cells, mediators of inflammation and parathyroid hormone. Much work remains to be done in this new field of knowledge before the role of vitamin D in the pathogenesis of diabetes mellitus is completely understood.

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Alfonso B, Liao E, Busta A, Poretsky L. Diabetes Metab Res Rev. 2009 Jul;25(5):417-9.

Telomerase, mitochondria and oxidative stress

Extract: Telomerase plays an important role in cellular proliferation capacity and survival under conditions of stress. A large part of this protective function is due to telomere capping and maintenance. Thus it contributes to cellular immortality in stem cells and cancer. Recently, evidence has accumulated that telomerase can contribute to cell survival and stress resistance in a largely telomere-independent manner. Telomerase has been shown to shuttle dynamically between different cellular locations. Under increased oxidative stress telomerase is excluded from the nucleus and can be found within the mitochondria. This phenotype correlates with decreased oxidative stress within telomerase expressing cells and improved mitochondrial function by currently largely unknown mechanisms. Our data suggest that mitochondrial protection could be an important non-canonical function for telomerase in cell survival and ageing. This review summarizes briefly our knowledge about extra-telomeric functions of telomerase and discusses the potential significance of its mitochondrial localization.

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Saretzki G. Exp Gerontol. 2009 Aug ;44(8):485-92.

Reviews

Clinical review: Realistic expectations and practical use of continuous glucose monitoring for the endocrinologist

Extract: CONTEXT: Real-time continuous glucose monitoring (CGM) has been available for type 1 diabetes for several years. This paper is a status report on our early experiences with this next technology. EVIDENCE ACQUISITION: The two major sources of data acquisition included PubMed search strategies and personal experience of the author from clinical experience. EVIDENCE SYNTHESIS: Data assessing CGM accuracy, short-term outcomes (12 wk), and longer term outcomes (6 months) are reported. Potential strategies for successful and efficient use in an office or clinic setting are also discussed. Practical aspects of CGM use (alarm settings, using glycemic trending information) are also reviewed. CONCLUSIONS: Accuracy of this technology has improved in the short amount of time it has been available. Six-month data suggest that patient selection is a key for success. Patients who do not understand or practice the basics of intensive insulin therapy have the greatest challenges. Those who do best watch the receiver frequently, continue with frequent home blood glucose monitoring, use the trending information to make insulin adjustments, and understand the limitations of the technology. With insurance reimbursement improving, CGM is gaining acceptance as an important tool for the management of type 1 diabetes. Like home blood glucose monitoring and insulin pump therapy, this technology by itself is not a panacea for diabetes control. However, it further adds to our ability to improve the lives of people with diabetes. Long-term, the hope is that this technology will pave the way for a "closed-loop" device.

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Hirsch IB. J Clin Endocrinol Metab. 2009 Jul;94(7):2232-8.

Exercise to reduce vasomotor and other menopausal symptoms: a review

Extract: Many women are reluctant to consider HRT as a therapeutic option for menopausal symptoms and are keen to use non-pharmacological treatments. Evidence from randomized controlled trials (RCTs) concerning the effects of aerobic exercise on vasomotor and other menopausal symptoms is limited but what evidence we do have suggests that aerobic exercise can improve psychological health and quality of life in vasomotor symptomatic women. In addition, several RCTs of middle-aged/menopausal-aged women have found that aerobic exercise can invoke significant improvements in several common menopause-related symptoms (e.g. mood, health-related QoL and insomnia), relative to non-exercise comparison groups. There is some evidence that alternative forms of low intensity exercise such as yoga are beneficial in reducing vasomotor symptoms and improving psychological well-being in menopausal women. Collectively, these RCTs highlight the broader potential that exercise could have for women during the menopause transition. Whilst both the Royal College of Obstetricians and Gynecologists in the UK and the North American Menopause Society have recommended that women be advised to consider aerobic exercise as a treatment for vasomotor menopausal symptoms, to make any evidence-based conclusions regarding the effectiveness of exercise in managing these symptoms, more high quality research is needed.

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Daley AJ, Stokes-Lampard HJ, Macarthur C. Maturitas. 2009 Jul 20;63(3):176-80.

Diagnostic tools for dementia

Extract: As population ageing means that dementia is becoming more prevalent, it is increasingly important that clinicians from all types of practice are familiar with assessing patients who have possible cognitive impairment. The diagnosis of the syndrome of dementia remains a clinical process, supplemented by relevant investigations including cognitive testing. This paper reviews some of the more commonly used tools for assessing cognition, behavior and overall functioning in patients with possible or established dementia. Several categories of instruments are considered, including brief screening tests, neuropsychological test batteries, scales for behavioural and psychiatric symptoms, and functional and global assessments. It is recommended that clinicians familiarize themselves with a small number of scales that can be readily employed in everyday practice.

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Hatfield CF, Dudas RB, Dening T. Maturitas. 2009 Jul 20;63(3):181-5.

Shared decision-making in the context of menopausal health: where do we stand?

Extract: Most health decisions occur in contexts of scientific uncertainty, the "grey zone" of decision-making and many decisions faced by menopausal women are no exception. These contexts are characterized either by scientific evidence that points to a balance between harms and benefits within or between options, or by the absence or insufficiency of scientific evidence: both situations give rise to degrees of uncertainty. Moreover, probabilities of risks and benefits in a population cannot be directly attributed at the individual level, and so uncertainty inevitably exists when considering individual decisions. Consequently, both clinicians and menopausal women need help in resolving uncertainty when facing clinical decisions. In other words, we argue that the ideal model for making decisions in the context of scientific uncertainty is the sharing of decisions between a clinician and a patient, a process known as shared decision-making (SDM). The objectives of this paper are to: (1) review the theoretical basis underlying effective interventions for SDM to occur in the context of menopausal health; (2) present the evidence regarding existing decision support interventions for menopausal women; and (3) identify implications for clinicians, health professional educators and researchers.

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Légaré F, Brouillette MH. Maturitas. 2009 Jul 20;63(3):169-75.