Association between insulin resistance and lean mass loss and fat mass gain in older men without diabetes mellitus

OBJECTIVES: To examine the associations between insulin resistance and changes in body composition in older men without diabetes mellitus. DESIGN: Longitudinal cohort study of older men participating in the Osteoporotic Fractures in Men (MrOS) study. SETTING: Six U.S. clinical centers. PARTICIPANTS: Three thousand one hundred thirty‐two ambulatory men aged 65 and older at baseline. MEASUREMENTS: Baseline insulin resistance was calculated for men without diabetes mellitus using the homeostasis model assessment of insulin resistance (HOMA‐IR). Total lean, appendicular lean, total fat, and truncal fat mass were measured using dual energy X‐ray absorptiometry scans at baseline and 4.6 ± 0.3 years later in 3,132 men with HOMA‐IR measurements. RESULTS: There was greater loss of weight, total lean mass, and appendicular lean mass and less gain in total fat mass and truncal fat mass with increasing quartiles of HOMA‐IR (P<.001 for trend). Insulin‐resistant men in the highest quartile had higher odds of 5% or more loss of weight (odds ratio (OR)=1.88, 95% confidence interval (CI)=1.46–2.43), total lean mass (OR=2.09, 95% CI=1.60–2.73) and appendicular lean mass (OR=1.57, 95% CI=1.27–1.95) and lower odds of 5% or more gain in total fat mass (OR=0.56, 95% CI=0.45–0.68) and truncal fat mass (OR=0.52, 95% CI=0.42–0.64) than those in the lowest quartile. These findings remained significant after accounting for age, site, baseline weight, physical activity, and change in physical activity. These associations were also independent of other metabolic syndrome features and medications. CONCLUSION: Greater lean mass loss and lower fat mass gain occurred in insulin‐resistant men without diabetes mellitus than in insulin‐sensitive men. Insulin resistance may accelerate age‐related sarcopenia.     

The British Diabetic Association Cohort Study, I: all-cause mortality in patients with insulin-treated diabetes mellitus.

AIMS: To assess mortality in patients with diabetes incident under the age of 30 years. METHODS: A cohort of 23 752 diabetic patients diagnosed under the age of 30 years from throughout the United Kingdom was identified during 1972-93 and followed up to February 1997. Following notification of deaths during this period, age- and sex-specific mortality rates, attributable risks and standardized mortality rates were calculated. RESULTS: The 23 752 patients contributed a total of 317 522 person-years of follow-up, an average of 13.4 years per subject. During follow-up 949 deaths occurred in patients between the ages of 1 and 84 years, 566 in males and 383 in females. All-cause mortality rates in the patients with diabetes exceeded those in the general population at all ages and within the cohort were higher for males than females at all ages except between 5 and 15 years. The relative risk of death (standardized mortality ratio, SMR), was higher for females than males at all ages, being 4.0 (95% CI 3.6-4.4) for females and 2.7 (2.5-2.9) for males overall, but reaching a peak of 5.7 (4.7-7.0) in females aged 20-29, and of 4.0 (3.1-5.0) in males aged 40-49. Attributable risks, or the excess deaths in persons with diabetes compared with the general population, increased with age in both sexes. CONCLUSIONS: This is the first study from the UK of young patients diagnosed with diabetes that is large enough to calculate detailed age-specific mortality rates. This study provides a baseline for further studies of mortality and change in mortality within the United Kingdom.     

The enigma of increased non-cancer mortality after weight loss in healthy men who are overweight or obese

Abstract. Nilsson PM, Nilsson J‐A, Hedblad B, Berglund G, Lindgärde F. (University Hospital, Malmö, Sweden). The enigma of increased non‐cancer mortality after weight loss in healthy men who are overweight or obese. J Intern Med 2002; 252: 70?78. Objective. To study effects on non‐cancer mortality of observational weight loss in middle‐aged men stratified for body mass index (BMI), taking a wide range of possible confounders into account. Design. Prospective, population based study. Setting. Male population of Malmö, Sweden. Participants. In all 5722 men were screened twice with a mean time interval of 6 years in Malmö, southern Sweden. They were classified according to BMI category at baseline (<21, 22?25, overweight: 26?30, and obesity: 30+ kg m^?2) and weight change category until second screening (weight stable men defined as having a baseline BMI ± 0.1 kg m^?2 year^?1 at follow‐up re‐screening). Main outcome measures. Non‐cancer mortality calculated from national registers during 16 years of follow‐up after the second screening. Data from the first year of follow‐up were excluded to avoid bias by mortality caused by subclinical disease at re‐screening. Results. The relative risk (RR; 95% CI) for non‐cancer mortality during follow‐up was higher in men with decreasing BMI in all subgroups: RR 2.64 (1.46?4.71, baseline BMI <21 kg m^?2), 1.39 (0.98?1.95, baseline BMI 22?25 kg m^?2), and 1.71 (1.18?2.47, baseline BMI 26+ kg m^?2), using BMI‐stable men as reference group. Correspondingly, the non‐cancer mortality was also higher in men with increasing BMI, but only in the obese group (baseline BMI 26+ kg m^?2) with RR 1.86 (1.31?2.65). In a subanalysis, nonsmoking obese (30+ kg m^?2) men with decreased BMI had an increased non‐cancer mortality compared with BMI‐stable obese men (Fischer's test: P=0.001). The mortality risk for nonsmoking overweight men who increased their BMI compared with BMI‐stable men was also significant (P=0.006), but not in corresponding obese men (P=0.094). Conclusions. Weight loss in self‐reported healthy but overweight middle‐aged men, without serious disease, is associated with an increased non‐cancer mortality, which seems even more pronounced in obese, nonsmoking men, as compared with corresponding but weight‐stable men. The explanation for these observational findings is still enigmatic but could hypothetically be because of premature ageing effects causing so‐called weight loss of involution.     

Frailty in older men: prevalence, progression, and relationship with mortality

OBJECTIVES: To describe the association between frailty and health status, the progression of frailty, and the relationship between frailty and mortality in older men. DESIGN: Cross-sectional and prospective cohort study. SETTING: Six U.S. clinical centers. PARTICIPANTS: Five thousand nine hundred ninety-three community-dwelling men aged 65 and older. MEASUREMENTS: Frailty was defined as three or more of the following: sarcopenia (low appendicular skeletal mass adjusted for height and body fat), weakness (grip strength), self-reported exhaustion, low activity level, and slow walking speed. Prefrail men met one or two criteria; robust men had none. Follow-up averaged 4.7 years. RESULTS: At baseline, 240 subjects (4.0%) were frail, 2,395 (40.0%) were prefrail, and 3,358 were robust (56.0%). Frail men were less healthy in most measures of self-reported health than prefrail or robust men. Frailty was somewhat more common in African Americans (6.6%) and Asians (5.8%) than Caucasians (3.8%). At the second visit, men who were frail at baseline tended to remain frail (24.2%) or die (37.1%) or were unable to complete the follow-up visit (26.2%); robust men tended to remain robust (54.4%). Frail men were approximately twice as likely to die as robust men (multivariate hazard ratio (MHR)=2.05, 95% confidence interval (CI)=1.55-2.72). Mortality risk for frail men was greater in all weight categories than for nonfrail men but was highest for normal-weight frail men (MHR=2.39, 95% CI=1.51-3.79, P for interaction=.01). The relationship between frailty and mortality was somewhat stronger in younger men than older men (P for interaction=.01). CONCLUSION: Frailty in older men is associated with poorer health and a greater risk of mortality.     

Bone loss predicts subsequent cognitive decline in older women: the study of osteoporotic fractures

OBJECTIVES: To determine whether the rate of bone loss predicts subsequent cognitive decline independently of baseline bone mass and whether apolipoprotein E (ApoE) genotype explains the association. DESIGN: A prospective cohort study. SETTING: Clinical centers in Baltimore, Maryland; Minneapolis, Minnesota; Pittsburgh, Pennsylvania; and Portland, Oregon. PARTICIPANTS: Four thousand four hundred sixty-two women aged 70 and older (mean = 75.8) participating in the Study of Osteoporotic Fractures. MEASUREMENTS: Total hipbone mineral density (BMD) was measured 2 and 6 years after enrollment (mean follow-up = 3.5 years), and expressed as annualized percentage rate of bone change. A modified Mini-Mental State Examination (mMMSE) was administered at 6 and 10 years (mean follow-up = 4.5 years) and defined cognitive decline as a decline of three or more points on repeat mMMSE score. ApoE genotype information was available on 883 women. RESULTS: Cognitive decline occurred in 12% of the women with the least bone loss (by quartile), 14% in the second, 16% in the third, and 20% in those with the greatest bone loss. After adjustment for age, education, stroke, functional status, estrogen use, body mass index, and smoking, the results were similar. Those who lost the most BMD were almost 40% more likely than women in the lowest quartile to develop cognitive decline in the multivariate model (odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.1-1.8). A similar association between hipbone loss and cognitive decline was observed in the multivariate model further adjusting for ApoE e4 (OR = 1.5, 95% CI = 0.8-2.7). CONCLUSIONS: Women with more rapid hipbone loss were more likely to develop cognitive decline than those who had lower rate of loss (or who gained bone mass). Differences in functional status, estrogen use, and ApoE did not explain this association. Further investigation is needed to determine the mechanisms that link osteoporosis and cognitive decline.     

Social deprivation and mortality in adults with diabetes mellitus

To investigate the relationship between measures of social deprivation and mortality in adults with diabetes, data from 2104 randomly selected adults (>16 years of age) with Type 1 and Type 2 diabetes mellitus from 8 hospital out-patient departments were analysed. A total of 38 % of subjects had Type 1 (diagnosed before the age of 36 years and treated with insulin), 55 % were male and 85 % Caucasian. During a follow-up period (mean (SD) of 8.4 (0.9) years), 293 (14 %) of the subjects died, the most commonly recorded cause of death being cardiovascular disease. Duration adjusted odds ratios (OR) and 95 % confidence intervals (CI) were calculated separately for Type 1 and Type 2 subjects. The mortality rates for men were higher than for women (Type 1: OR 1.27, CI 0.61–2.62; Type 2: OR 1.79, CI 1.27–2.52); were higher for those of lower vs higher social class (Type 1: OR 1.34, CI 0.61–2.96; Type 2: OR 2.0, CI 1.41–2.85); and were higher for those who left school before 16 years of age compared to those who left school at or after 16 years of age (Type 1: OR 3.98, CI 1.96–8.06; Type 2: OR 2.86, CI 1.93–4.25). Subjects who were unemployed had a higher mortality rate than those employed at the time of the study (Type 1: OR 3.10, CI 1.67–5.79; Type 2: OR 2.88, CI 2.12–3.91) and those living in council housing had a greater mortality than those who were living in other types of housing (Type 1: OR 2.57, CI 1.35–4.91, Type 2: OR 2.76, CI 2.05–3.73). Also for both Type 1 and Type 2 subjects mortality was significantly higher in those subjects who had a least one diabetic complication at baseline and reported one or more hospital admissions in the previous year and in Type 2 subjects with poor glycaemic control. After adjusting for duration of diabetes, hospital admissions, and the presence of diabetic complications, being unemployed, male, in poor glycaemic control (Type 2 only), and less educated were significant risk factors for mortality (p<0.001). These results suggest that there are important indicators of social deprivation which predict mortality over and above diabetic health status itself. Locally targeted action will be required if these inequalities in health experienced by people with diabetes are to be reduced. © 1998 John Wiley & Sons, Ltd.     

Benefits of moderate weight loss in patients with type 2 diabetes

Weight loss is a primary goal of therapy in overweight patients with type 2 diabetes. This review examines whether positive patient outcomes are observed even after relatively small amounts of weight loss, that is, weight loss being more easily attainable in practice. Clinical studies demonstrate that therapeutic benefit rises with increasing weight loss, but that losses as low as 0.45–4 kg (1–9 lb) have positive effects on metabolic control, cardiovascular risk factors and mortality rates. Even the intention to lose weight, without significant success, can improve outcomes in patients with diabetes, presumably because of the healthy behaviours associated with the attempt. The current data support a continued focus on weight loss, including moderate weight loss, as a key component of good care for overweight patients with type 2 diabetes.     

Functional status and health outcomes in older americans with diabetes mellitus

OBJECTIVES: To determine how baseline functional status affects health outcomes in older adults with diabetes mellitus (DM). DESIGN: Nationally representative cross-sectional and longitudinal health interview survey. SETTING: Waves I (1993) and II (1995) of the Assets and Health Dynamics of the Oldest Old Survey (AHEAD) in the United States. PARTICIPANTS: AHEAD respondents aged 70 and older (n = 7,447, including 995 with DM). MEASUREMENTS: At baseline, the entire sample was divided into three groups: high-functioning group, defined as having no physical limitations or instrumental activities of daily living/activities of daily living (IADL/ADL) disabilities (39%); low-functioning group, having three or more limitations or IADL/ADL disabilities (24%); and intermediate-functioning group, those in the middle (36%). Older adults with and without DM, within each of the functioning groups, were compared at 2-year follow-up with respect to demographic characteristics, weight/body mass index, baseline and incident chronic diseases and conditions, and follow-up functioning. RESULTS: Of people aged 70 and older, 28% with DM and 41% without were high functioning; 38% with DM and 22% without were low functioning (both P <.001). High-functioning people with DM remained high functioning at 2 years but had a significantly higher incidence of heart disease and mortality than high-functioning people without DM. Low-functioning people with DM were significantly more likely to have vascular comorbidities at baseline than low-functioning people without DM, but their 2-year outcomes were similar. The intermediate-functioning group showed the most differences between those with and without DM; those with DM were significantly (P <.01) more likely to have baseline vascular disease, low cognitive performance, increased incident vascular disease, and significantly worse 2-year functioning and to have experienced falls (P <.001). CONCLUSION: Differences in baseline functional status in older adults with DM were associated with outcome differences. High-functioning older people with DM tended to remain high functioning but demonstrated significantly higher incidence of heart disease and mortality than those without DM, whereas low-functioning people with and without DM had similar outcomes. However, intermediate-functioning older diabetics had worse health and functioning outcomes than a similarly impaired group without DM. DM management adjusted to functional status can potentially address the most-relevant outcomes in the heterogeneous older population with DM.     

Glucose, blood pressure, and lipid control in older people with and without diabetes mellitus: the Cardiovascular Health Study

OBJECTIVES: To determine the prevalence of cardiovascular risk-factor treatment and control in older adults with normal fasting glucose, impaired fasting glucose, and diabetes mellitus and whether those with diabetes mellitus had better risk factor control than older adults with normal fasting glucose. DESIGN: Secondary analysis of data from population-based, prospective cohort study of risk factors for cardio-vascular and cerebrovascular disease in older people (Cardiovascular Health Study). SETTING: Community-based. PARTICIPANTS: Community-dwelling adults aged 65 and older. MEASUREMENTS: Fasting plasma glucose, serum cholesterol and its subfractions, systolic and diastolic blood pressures, and body mass index. RESULTS: There were 579 (18%) cohort members with diabetes mellitus (77% receiving antidiabetic medication, 23% with fasting glucose > or =126 mg/dL and no treatment), 213 (6%) with impaired fasting glucose, and 2,582 (77%)with normal fasting glucose. Of diabetic participants, 12% had recommended fasting glucose levels of less than 110 mg/dL. Of participants with hypertension, a larger proportion of diabetic participants than nondiabetic participants (89% versus 75%, P < .01) was treated with antihypertensive agents, but a smaller proportion of diabetic participants had recommended blood pressure levels of 129/85 mmHg or lower than nondiabetic participants had recommended blood pressure levels of 139/89 mmHg or lower (27% vs 48%, P < .01). Diabetic dyslipidemic participants were treated less often with lipid-lowering therapy (26% versus 55%, P < .01) and achieved recommended low-density lipoprotein goals less often (8%versus 54%, P < .01) than nondiabetic dyslipidemic participants. CONCLUSIONS: Overall, treatment and control of cardiovascular risk factors were suboptimal in this older population, especially among those with diabetes mellitus. Optimizing risk-factor control can improve health outcomes in older adults with and without diabetes mellitus.     

A prospective study of Type 2 diabetes and depressive symptoms in the elderly: the Rancho Bernardo Study.

AIMS: The association between Type 2 diabetes and depressive symptoms was examined prospectively to assess possible causal relationships between the two diseases. METHODS: A cohort of 971 men and women aged 50 and older from the adult population of Rancho Bernardo, California had an oral glucose tolerance test and completed the Beck Depression Inventory (BDI) at two clinic visits, 1984-87 and 1992-96. RESULTS: Depressive symptoms at baseline were associated with higher follow-up levels of non-fasting plasma glucose (P = 0.001) and an increased risk of developing Type 2 diabetes [odds ratio (OR) = 2.50; 95% confidence interval (CI) = 1.29-4.87], independent of sex, age, exercise and body mass index. Conversely, baseline non-fasting plasma glucose was not significantly associated with follow-up depressive symptoms and Type 2 diabetes at baseline was not significantly associated with the onset of BDI scores > or = 11 by the second visit (OR = 0.73; 95% CI = 0.41-1.30). CONCLUSIONS: Depressed mood is more likely to be a risk factor for Type 2 diabetes in older adults than the reverse.