Rita R. Kalyani

Association of Diabetes, Comorbidities, and A1C With Functional Disability in Older Adults: Results from the National Health and Nutrition Examination Survey (NHANES), 1999–2006

OBJECTIVE To examine the relationship of diabetes and functional disability in older adults and the possible mediating roles of comorbidities and A1C. RESEARCH DESIGN AND METHODS We analyzed data from a nationally representative sample of 6,097 participants aged ≥60 years in the National Health and Nutrition Examination Survey, 1999–2006. Diabetes was defined by self-report. Disability was defined as difficulty performing a physical task. We evaluated disability by grouping 19 physical tasks into five functional groups: lower-extremity mobility (LEM), general physical activities (GPA), activities of daily living (ADL), instrumental activities of daily living (IADL), and leisure and social activities (LSA). RESULTS Older U.S. adults with diabetes had the greatest disability in GPA (prevalence 73.6% [95% CI 70.2–76.9]), followed by LEM (52.2% [48.5–55.9]), IADL (43.6% [40.1–47.2]), ADL (37.2% [33.1–41.3]), and LSA groups (33.8% [30.8–36.9]). Diabetes was associated with two to three times increased odds of disability across functional groups (all P < 0.05). Comorbidities, mostly cardiovascular disease and obesity, and poor glycemic control (A1C ≥8%) together explained up to 85% of the excess odds of disability associated with diabetes, whereas poor glycemic control alone explained only ∼10% of the excess odds. Adjustment for comorbidities, A1C, and diabetes duration fully attenuated the associations of diabetes with disability in all functional groups (all P > 0.05). CONCLUSIONS Older adults with diabetes have a high prevalence of disabilities with variable associations attributable to comorbidities and A1C. Aggressive management of cardiovascular risk factors and obesity may significantly reduce the burden of disability in this population.

Vitamin D Treatment for the Prevention of Falls in Older Adults: Systematic Review and Meta‐Analysis

OBJECTIVES: To systematically review and quantitatively synthesize the effect of vitamin D therapy on fall prevention in older adults.

Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases

The term sarcopenia refers to the loss of muscle mass that occurs with ageing. On the basis of study results showing that muscle mass is only moderately related to functional outcomes, international working groups have proposed that loss of muscle strength or physical function should also be included in the definition. Irrespective of how sarcopenia is defined, both low muscle mass and poor muscle strength are clearly highly prevalent and important risk factors for disability and potentially mortality in individuals as they age. Many chronic diseases, in addition to ageing, could also accelerate decrease of muscle mass and strength, and this effect could be a main underlying mechanism by which chronic diseases cause physical disability. In this Review, we address both age-related and disease-related muscle loss, with a focus on diabetes and obesity but including other disease states, and potential common mechanisms and treatments. Development of treatments for age-related and disease-related muscle loss might improve active life expectancy in older people, and lead to substantial health-care savings and improved quality of life.

Androgen deficiency, diabetes, and the metabolic syndrome in men.

Purpose of reviewThe burden of androgen deficiency in men with diabetes and the metabolic syndrome has become increasingly apparent in population-based studies. This article focuses on the mechanisms underlying the interdependent relationship between these conditions. Recent findingsVarious definitions of hypogonadism, the metabolic syndrome and diabetes have been proposed and are used in the literature. Cross-sectional studies have found that between 20 and 64% of men with diabetes have hypogonadism, with higher prevalence rates found in the elderly. Hypogonadism can be a risk factor for the development of diabetes and the metabolic syndrome through various mechanisms including changes in body composition; androgen receptor polymorphisms; glucose transport; and reduced antioxidant effect. Conversely, diabetes and the metabolic syndrome can be risk factors for hypogonadism through some similar but mostly distinct mechanisms, such as increased body weight; decreased sex hormone binding globulin levels; suppression of gonadotrophin release or Leydig cell testosterone production; cytokine-mediated inhibition of testicular steroid production; and increased aromatase activity contributing to relative estrogen excess. SummaryThe relationship between diabetes, the metabolic syndrome and androgen deficiency is complex. Testosterone supplementation, by either oral or intramuscular routes and through exogenous or endogenous delivery, has a promising role in this population although further clinical trials are needed.

The Association of Endogenous Sex Hormones, Adiposity, and Insulin Resistance with Incident Diabetes in Postmenopausal Women

CONTEXT In postmenopausal women, endogenous bioavailable testosterone (T) and estradiol (E2) have been positively associated, and SHBG has been negatively associated, with incident type 2 diabetes (T2DM). Previous studies have not explored possible factors explaining these relationships. OBJECTIVE Our objective was to examine the association of endogenous sex hormones with incident T2DM in postmenopausal women and possible explanatory factors. DESIGN, SETTING, AND PARTICIPANTS The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective study that included 1612 postmenopausal women aged 45-84 yr, followed between the years 2000-2006, who were not taking hormone replacement therapy, had no prevalent cardiovascular disease or diabetes, and had complete ascertainment of sex hormones. MAIN OUTCOME MEASURES T2DM was defined based on fasting glucose and/or treatment for diabetes. RESULTS There were 116 incident cases of diabetes during follow-up. Across higher quartiles of bioavailable T and E2 and lower quartiles of SHBG, we found significantly greater hazards of developing incident T2DM (all P for trend <or=0.001). After adjustment for body mass index and insulin resistance estimated by homeostasis model assessment of insulin resistance, bioavailable T was no longer associated with incident T2DM. The associations of E2 and SHBG with incident T2DM were partially explained by body mass index and insulin resistance but persisted in fully adjusted models (both P for trend <0.02). Dehydroepiandrosterone had no relationship with incident T2DM. CONCLUSIONS Adiposity and insulin resistance explained most of the association of bioavailable T but only partially explained the associations of E2 and SHBG with incident T2DM among postmenopausal women.

Frailty in Older Adults: A Nationally Representative Profile in the United States

BACKGROUND Frailty assessment provides a means of identifying older adults most vulnerable to adverse outcomes. Attention to frailty in clinical practice is more likely with better understanding of its prevalence and associations with patient characteristics. We sought to provide national estimates of frailty in older people. METHODS A popular, validated frailty phenotype proposed by Fried and colleagues was applied to 7,439 participants in the 2011 baseline of the National Health and Aging Trends Study, a national longitudinal study of persons aged 65 and older. All measures drew on a 2-hour in-person interview. Weighted estimates of frailty prevalence were obtained. RESULTS Fifteen percent (95% CI: 14%, 16%) of the older non-nursing home population is frail, and 45% is prefrail (95% CI: 44%, 47%). Frailty is more prevalent at older ages, among women, racial and ethnic minorities, those in supportive residential settings, and persons of lower income. Independently of these characteristics, frailty prevalence varies substantially across geographic regions. Chronic disease and disability prevalence increase steeply with frailty. Among the frail, 42% were hospitalized in the previous year, compared to 22% of the prefrail and 11% of persons considered robust. Hip, back, and heart surgery in the last year were associated with frailty. Over half of frail persons had a fall in the previous year. CONCLUSIONS Our findings support the importance of frailty in late-life health etiology and potential value of frailty as a marker of risk for adverse health outcomes and as a means of identifying opportunities for intervention in clinical practice and public health policy.

Frailty assessment instruments: Systematic characterization of the uses and contexts of highly-cited instruments.

The medical syndrome of frailty is widely recognized, yet debate remains over how best to measure it in clinical and research settings. This study reviewed the frailty-related research literature by (a) comprehensively cataloging the wide array of instruments that have been utilized to measure frailty, and (b) systematically categorizing the different purposes and contexts of use for frailty instruments frequently cited in the research literature. We identified 67 frailty instruments total; of these, nine were highly-cited (≥ 200 citations). We randomly sampled and reviewed 545 English-language articles citing at least one highly-cited instrument. We estimated the total number of uses, and classified use into eight categories: risk assessment for adverse health outcomes (31% of all uses); etiological studies of frailty (22%); methodology studies (14%); biomarker studies (12%); inclusion/exclusion criteria (10%); estimating prevalence as primary goal (5%); clinical decision-making (2%); and interventional targeting (2%). The most common assessment context was observational studies of older community-dwelling adults. Physical Frailty Phenotype was the most used frailty instrument in the research literature, followed by the Deficit Accumulation Index and the Vulnerable Elders Survey. This study provides an empirical evaluation of the current uses of frailty instruments, which may be important to consider when selecting instruments for clinical or research purposes. We recommend careful consideration in the selection of a frailty instrument based on the intended purpose, domains captured, and how the instrument has been used in the past. Continued efforts are needed to study the validity and feasibility of these instruments.

The Incidence of, risk factors for, and sequelae of herpes zoster among HIV patients in the highly active antiretroviral therapy era

Background:Whereas the incidence, risk factors, and clinical sequelae of herpes zoster have been studied in the general population and in HIV patients in the era before highly active antiretroviral therapy (HAART), they have yet to be fully understood in the current era of HAART. Methods:We conducted a retrospective cohort study of patients enrolled in an urban HIV clinic between January 1, 1997 and December 31, 2001. Patients with an episode of herpes zoster during this period were identified, and their charts were reviewed. A nested case-control analysis was used to assess factors associated with an initial episode of herpes zoster. Multivariate conditional logistic regression analyses were used to assess risk factors for zoster. Logistic regression was performed to assess factors associated with complicated zoster. Results:Two hundred eighty-two episodes of herpes zoster were identified in 239 patients. Of these episodes, 158 were new occurrences of zoster and 124 were recurrent zoster events. The incidence of zoster during the study period was 3.2 per 100 person-years of follow-up. The incident cases reflected the clinic population, with most patients being male (63%) and African American (77%) and having injection drug use as their HIV risk factor (49%). The mean age of the patients was 41 years. Sixty-seven percent of patients had single dermatomal involvement, and the thorax was involved in 41%. In multivariate regression, being on HAART (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.65 to 3.49) and a CD4 count of 50 to 200 cells/mm3 (OR = 2.69, 95% CI: 1.44 to 5.01) compared with a CD4 count less than 50 cells/mm3 were associated with an increased risk of zoster. Twenty-eight patients (18%) developed post-herpetic neuralgia (PHN), and 29 patients (18%) had other complications. Male-to-male sex as an HIV risk factor (P = 0.02) and being on HAART at a zoster episode (P = 0.03) were protective against complicated zoster. Conclusions:Our results suggest that zoster infection rates have not changed in the current HAART era but that a significant percentage of patients develop complications, particularly PHN, which is quite remarkable considering the young age of our population.

Quadriceps Strength, Quadriceps Power, and Gait Speed in Older U.S. Adults with Diabetes Mellitus:: Results from the National Health and Nutrition Examination Survey, 1999-2002

To examine the independent association between diabetes mellitus (and its duration and severity) and quadriceps strength, quadriceps power, and gait speed in a national population of older adults.

Sex Differences in Diabetes and Risk of Incident Coronary Artery Disease in Healthy Young and Middle-Aged Adults

OBJECTIVE Controversy exists about the coronary artery disease (CAD) risk conveyed by diabetes in young and middle-aged women. We investigated sex differences in CAD by diabetes status among healthy individuals with different underlying risks of heart disease. RESEARCH DESIGN AND METHODS We examined subjects aged <60 years without CAD at enrollment in the high-risk GeneSTAR Study (n = 1,448; follow-up ∼12 years), Multi-Ethnic Study of Atherosclerosis (MESA; n = 3,072; follow-up ∼7 years), and National Health and Nutrition Examination Survey III (NHANES III) Mortality Follow-up Study (n = 6,997; follow-up ∼15 years). Diabetes was defined by report, hypoglycemic use, and/or fasting glucose ≥126 mg/dL. The outcome was any CAD event during follow-up (fatal CAD in NHANES). RESULTS In the absence of diabetes, CAD rates were lower among women in GeneSTAR, MESA, and NHANES (4.27, 1.66, and 0.40/1,000 person-years, respectively) versus men (11.22, 5.64, and 0.88/1,000 person-years); log-rank P < 0.001 (GeneSTAR/MESA) and P = 0.07 (NHANES). In the presence of diabetes, CAD event rates were similar among women (17.65, 7.34, and 2.37/1,000 person-years) versus men (12.86, 9.71, and 1.83/1,000 person-years); all log-rank P values > 0.05. Adjusting for demographics, diabetes was associated with a significant four- to fivefold higher CAD rate among women in each cohort, without differences in men. In meta-analyses of three cohorts, additionally adjusted for BMI, smoking, hypertension, HDL, and non-HDL cholesterol, antihypertensive and cholesterol-lowering medication use, the hazard ratio of CAD in men versus women among nondiabetes was 2.43 (1.76–3.35) and diabetes was 0.89 (0.43–1.83); P = 0.013 interaction by diabetes status. CONCLUSIONS Though young and middle-aged women are less likely to develop CAD in the absence of diabetes, the presence of diabetes equalizes the risk by sex. Our findings support aggressive CAD prevention strategies in women with diabetes and at similar levels to those that exist in men.