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Age as independent determinant of glucose tolerance.

It has been proposed that the decline in glucose tolerance with age is not a primary aging effect but is secondary to a combination of other age-associated characteristics, i.e., disease, medication, obesity, central and upper-body fat deposition, and inactivity. To test this hypothesis, we first eliminated from analysis the Baltimore Longitudinal Study of Aging participants with identifiable diseases or medications known to influence glucose tolerance. Seven hundred forty-three men and women, aged 17-92 yr, remained for analysis. As indices of fatness, body mass index and percent body fat were determined. As indices of body fat distribution, waist-hip ratio and subscapular triceps skin-fold ratio were calculated. As indices of fitness, physical activity level, determined by detailed questionnaire, and maximum 02 consumption were calculated. We tested whether the effect of age on glucose tolerance remains when data were adjusted for fatness, fitness, and fat distribution; 2-h glucose values were 6.61, 6.78, and 7.83 mM for young (17-39 yr), middle-aged (40-59 yr), and old (60-92 yr) men and 6.22, 6.22, and 7.28 mM for the three groups of women, respectively. The differences between the young and middle-aged groups were not significant, but the old groups had significantly higher values than young or middle-aged groups. Fatness, fitness, and fat distribution can account for the decline in glucose tolerance from the young adult to the middle-aged years. However, age remains a significant determinant of the further decline in glucose tolerance of healthy old subjects.

Adipose Tissue↗

Obesity and aging.

This review focuses on studies that pertain to obesity and aging. The prevalence of obesity in the elderly is discussed, with an emphasis on body-fat distribution as it relates to morbidity and mortality rates. Treatment options, such as physical activity, growth hormones, and drug therapy, are briefly mentioned. A section that covers some of the most recent issues pertaining to the neuroregulation of feeding and energy expenditure is included. Finally, we briefly discuss anorexia in the aged.

Adult↗

[Blood lipid levels and atherogenic risk in an open urban population].

We present the results of a population based survey in a low income area of Mexico City. The equivalent of three census tracts were identified and enumerated. The age eligible population (35-64 yrs) in the zone comprised 2253 subjects. A household interview was obtained in 94.8% and a physical exam with laboratory determinations was performed in 62.6% of the total population. The total number of cases studied was 1411 of which 565 were males and 846 were females. Age group distribution was as follows: group 1 (35-44 y) 235 men, 367 women; group 2 (45-54 y) 203 men, 289 women; and group 3 (55-64 y) 127 men, 190 women. The physical exam included the following measurements: height, weight, blood pressure measured with a random zero sphygmomanometer, subscapular and triceps skinfold measurements, and waist and hip circumferences. The body mass index (BMI) was calculated according to a standard formula; the subscapular/triceps ratio was used as centrality index and the waist/hip ratio was used to indicate upper/lower body fat distribution. In addition, the following blood lipids were measured following a 12 hr fast: total and HDL, LDL, VLDL-cholesterol as well as triglycerides. The mean BMI for women was 28.9 kg/m2, for men it was 27 kg/m2. The subscapular/triceps skinfold ratio revealed a predominantly central fat distribution pattern in both sexes. The waist/hip circumference ratio showed a predominantly lower fat distribution pattern also in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Obesity and androgens: facts and perspectives.

OBJECTIVE: This review discusses androgen status in male and female obesity, according to their specific phenotype, and the main mechanisms responsible. DESIGN: Published data in the literature of the last 20 years represented the basis of most of the data and concepts incorporated in the review. RESULT(S): Obesity is associated with profound alterations in androgen secretion, transport, metabolism, and action, according to a dichotomous behavior depending on sex. Obese men are characterized by a progressive decrease of testosterone levels with increasing body weight, whereas obese women, particularly those with the abdominal phenotype, tend to develop a condition of functional hyperandrogenism. Reduced sex hormone-binding globulin synthesis and circulating blood levels represent the sole common mechanism which is responsible in both sexes. Among other still partially undefined factors, mechanisms potentially responsible for the sex dichotomy in androgen levels involve specific alterations of gonadotropin secretion, estrogens, the hypothalamic-pituitary-adrenal axis, leptin, androgen receptors, specific steroidogenic enzymes in the peripheral tissues, and, possibly, ghrelin. In both sexes, androgens play an important role in determining the sex-dependent pattern of body fat distribution. Moreover there are theoretical possibilities that low testosterone in men and high free testosterone fraction in women may play a role in the development of the metabolic syndrome. This is exemplified by the well defined association between obesity and other features of the metabolic syndrome in women with polycystic ovary syndrome and in hypogonadal men. The effects of androgen and antiandrogens in obese men and women also represent arguments in favor of this association. CONCLUSION(S): Given the fundamental role of sex hormones in the regulation of body composition, fuel homeostasis, and reproduction in humans, more emphasis should be placed on the potential role of androgen dysregulation in the pathophysiology of different obesity phenotypes and the metabolic syndrome.

Clinical Trials as Topic↗

Central obesity and coronary heart disease in men.

The relation between central body fat distribution, determined by measurement of subscapular skinfold thickness (SSF), and the development of definite coronary heart disease (CHD) was examined after 12 years of follow-up in a cohort of 7692 men who participated in the Honolulu Heart Program. The risk of incident coronary events was directly related to SSF. Compared with men in the lowest tertile of SSF, those in the middle tertile experienced a 70% excess of definite CHD. For those in the highest tertile, the excess more than doubled. For a given level of body mass index (BMI), SSF remains a significant and independent predictor of definite CHD, even after adjustment for age, total cholesterol, glucose, triglycerides, hypertensive status, and cigarette smoking. In contrast, the independent effect of BMI was not significant after adjustment for SSF. Thus centrally obese individuals are at increased risk of CHD, independent of BMI.

Body Height↗

Insulin resistance, body mass index, waist circumference are independent risk factor for high blood pressure.

OBJECTIVES: The purpose of the present study was to investigate the relationships between blood pressure (BP), insulin resistance as determined by a homeostasis model (HOMA-IR), and body fat distribution. METHODS: Anthropometric indices of adiposity, metabolic variables (fasting serum insulin and a homeostasis model assessment [HOMA] index of insulin sensitivity), BP and several cardiovascular risk factors were measured during a cross sectional survey of 53477 apparently healthy Korean subjects who requested a health status check. Hypertension was defined as a systolic BP > or = 140 mmHg or a diastolic BP > or = 90 mmHg and we excluded the subjects taking BP-lowering medication. RESULTS: Systolic and diastolic blood pressure (SBP, DBP) were positively and significantly associated with age, body mass index, waist circumference, and waist/hip ratio. In addition, SBP and DBP were positively associated with fasting serum insulin levels and the HOMA index. By multiple regression analysis age, waist circumference, body mass index, HOMA index and female sex were independently associated with either increased SBP or DBP. When the population is divided into quintiles according to insulin resistance (measured by HOMA analysis) prevalence of hypertension in the second, third, fourth and fifth quintiles compared to subjects in the first quintile are 1.004(95% CI 0.875-1.152, p = 0.957), 1.200(95% CI 1.052-1.369, p = 0.007), 1.312(95% CI 1.151-1.494 p < 0.001 ), and 1.603(95% CI 1.408-1.825 p < 0.001). In addition age, sex, body mass index and waist circumference were found to be significantly associated with hypertension. CONCLUSION: Our results showed that insulin resistance, body mass index and waist circumference are independent risk factors of a high BP in Koreans.

Adult↗

Body mass index is associated with the development of the post-thrombotic syndrome.

Post-thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT). Little is known about prognostic factors that might identify patients at high risk for the development of PTS. Body mass index (BMI) has been previously reported to be associated to the development of PTS. The aim of this study was to assess the association between BMI and other anthropometric parameters and PTS in a general population of DVT patients. In a prospective cohort study, 83 consecutive patients with objective diagnosis of DVT underwent physical examination. BMI was recorded at baseline and at 12 months, and waist circumference was recorded at 12 months to assess individual patterns of body fat distribution. The presence of PTS at 12 months was ascertained using a validated clinical scale. Sixty-three patients (75.9%) were overweight or obese at 12 months, 60 (72.3%) had a weight gain over 1 year. Twenty patients developed PTS (24.1%). Mean BMI was significantly higher in patients who developed PTS than in patients who did not (29.6 and 27.2 Kg/m(2), respectively, p = 0.022). A BMI of > 28 Kg/m(2) predicted early onset of PTS (OR 3.54, 95% CI 1.07-12.08, p = 0.017). Neither patterns of fat distribution nor weight gain in 1 year were correlated with PTS (p = 0.918 and p = 0.775, respectively). BMI is significantly correlated with the development of PTS. Patients with DVT should be encouraged to avoid weight gain. Reducing patient weight might be an important strategy to prevent PTS.

Adult↗

PLTP activity in premenopausal women. Relationship with lipoprotein lipase, HDL, LDL, body fat, and insulin resistance.

Plasma phospholipid transfer protein (PLTP) is thought to play a major role in the facilitated transfer of phospholipids between lipoproteins and in the modulation of high density lipoprotein (HDL) particle size and composition. However, little has been reported concerning the relationships of PLTP with plasma lipoprotein parameters, lipolytic enzymes, body fat distribution, insulin, and glucose in normolipidemic individuals, particularly females. In the present study, 50 normolipidemic healthy premenopausal females were investigated. The relationships between the plasma PLTP activity and selected variables were assessed. PLTP activity was significantly and positively correlated with low density lipoprotein (LDL) cholesterol (r(s) = 0.53), apoB (r(s) = 0.44), glucose (r(s) = 0.40), HDL cholesterol (r(s) = 0.38), HDL(3) cholesterol (r(s) = 0.37), lipoprotein lipase activity (r(s) = 0.36), insulin (r(s) = 0.33), subcutaneous abdominal fat (r(s) = 0.36), intra-abdominal fat (r(s) = 0.29), and body mass index (r(s) = 0.29). HDL(2) cholesterol, triglyceride, and hepatic lipase were not significantly related to PLTP activity. As HDL(2) can be decreased by hepatic lipase and hepatic lipase is increased in obesity with increasing intra-abdominal fat, the participants were divided into sub-groups of non-obese (n = 35) and obese (n = 15) individuals and the correlation of PLTP with HDL(2) cholesterol was re-examined. In the non-obese subjects, HDL(2) cholesterol was found to be significantly and positively related to PLTP activity (r(s) = 0.44). Adjustment of the HDL(2) values for the effect of hepatic lipase activity resulted in a significant positive correlation between PLTP and HDL(2) (r(s) = 0.41), indicating that the strength of the relationship between PLTP activity and HDL(2) can be reduced by the opposing effect of hepatic lipase on HDL(2) concentrations. We conclude that PLTP-facilitated lipid transfer activity is related to HDL and LDL metabolism, as well as lipoprotein lipase activity, adiposity, and insulin resistance.

Adipose Tissue↗

[Adipose tissue: an innervated endocrine gland].

Until recently, adipose tissue was considered to function as a passive store of triglycerides and therefore of calories. Fascinating research over the past ten years has altered this traditional perspective. Adipose tissue has been shown to produce hormones. Leptin was discovered in 1994; one of its main functions is to adapt the organism to starvation. Sympathetic nerve fibres were shown to innervate adipose tissue and to facilitate lipolysis leading to the release of glycerol and free fatty acids. In addition, parasympathetic innervation of adipose tissue was recently demonstrated, with anabolic effects. Different sets of autonomic neurons in the brain stem appear to innervate either the abdominal or the subcutaneous fat compartment. This may be the anatomical substrate for the hitherto unexplained regulation of body fat distribution (subcutaneous versus intra-abdominal). Moreover, fat distribution under physiological conditions (sex steroids, glucocorticoids) and pathological conditions (e.g., AIDS lipodystrophy, Cushing syndrome) might be mediated via the central nervous system. The developments in this research area have the potential to increase our insights into the pathogenesis of metabolic disorders such as hypertriglyceridaemia and type-2 diabetes mellitus.

Adipose Tissue↗

Selected metabolic and morphologic complications associated with highly active antiretroviral therapy.

Metabolic and morphologic changes have been described in patients with human immunodeficiency virus (HIV) infection. In the short term, these disorders can be debilitating and may require medical intervention, including alterations in antiretroviral therapy regimens. The long-term consequences have not been fully realized, but are important, particularly in the era of durable HIV disease management with highly active antiretroviral therapy. This review focuses on 3 of the important morphologic or metabolic changes, namely alterations in body fat distribution, dyslipidemia, and lactic acidosis. The prevalence of each of these disorders remains unknown due to varied definitions and difficulty in recognition of the conditions for both the patient and the clinician. Treatment regimens directed at these abnormalities are being developed, but clinical trials are needed to fully ascertain the efficacy and safety of such interventions.

Acidosis, Lactic↗

Obesity as a potential risk factor for adenocarcinomas and squamous cell carcinomas of the uterine cervix.

BACKGROUND: Hormonal factors may play a more prominent role in cervical adenocarcinoma than squamous cell carcinoma. The authors evaluated whether obesity, which can influence hormone levels, was associated with adenocarcinoma and squamous cell carcinoma. METHODS: This case-control study included 124 patients with adenocarcinoma, 139 matched patients with squamous cell carcinoma, and 307 matched community control participants. All participants completed interviews and provided cervicovaginal samples for human papillomavirus (HPV) testing. Polytomous logistic regression-generated odds ratios (ORs) and 95% confidence intervals (95% CIs) for self-reported height and weight, body mass index (BMI; kg/m(2)), and measured waist-to-hip ratio (WHR) for both histologic types were adjusted and stratified for HPV and other confounders. RESULTS: Height, weight, BMI, and WHR were positively associated with adenocarcinoma. BMI >or= 30 kg/m(2) (vs. BMI < 25 kg/m(2); OR, 2.1 and 95% CI, 1.1-3.8) and WHR in the highest tertile (vs. the lowest tertile; OR, 1.8 and 95% CI, 0.97-3.3) were associated with adenocarcinoma. Neither height nor weight was found to be associated with squamous cell carcinoma, and associations for BMI >or= 30 kg/m(2) (OR, 1.6) and WHR in the highest tertile (OR, 1.6) were weaker and were not statistically significant. Analyses using only HPV positive controls showed similar associations. The data were adjusted for and stratified by screening, but higher BMI and WHR were associated with higher disease stage at diagnosis, even among recently and frequently screened patients with adenocarcinoma. Thus, residual confounding by screening could not be excluded as an explanation for the associations. CONCLUSIONS: Obesity and body fat distribution were associated more strongly with adenocarcinoma than with squamous cell carcinoma. Although questions about screening remain, obesity may have a particular influence on the risk of glandular cervical carcinoma.

Adenocarcinoma↗

Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process?

Age-dependent changes in insulin action and body fat distribution are risk factors for the development of type 2 diabetes. To examine whether the accumulation of visceral fat (VF) could play a direct role in the pathophysiology of insulin resistance and type 2 diabetes, we monitored insulin action, glucose tolerance, and the expression of adipo-derived peptides after surgical removal of VF in aging (20-month-old) F344/Brown Norway (FBN) and in Zucker Diabetic Fatty (ZDF) rats. As expected, peripheral and hepatic insulin action were markedly impaired in aging FBN rats, and extraction of VF (accounting for approximately 18% of their total body fat) was sufficient to restore peripheral and hepatic insulin action to the levels of young rats. When examined at the mechanistic level, removal of VF in ZDF rats prevented the progressive decrease in insulin action and delayed the onset of diabetes, but VF extraction did not alter plasma free fatty acid levels. However, the expression of tumor necrosis factor-alpha and leptin in subcutaneous (SC) adipose tissue were markedly decreased after VF removal (by approximately three- and twofold, respectively). Finally, extracted VF retained approximately 15-fold higher resistin mRNA compared with SC fat. Our data suggest that insulin resistance and the development of diabetes can be significantly reduced in aging rats by preventing the age-dependent accumulation of VF. This study documents a cause-and-effect relationship between VF and major components of the metabolic syndrome.

Abdomen↗

A low sympathoadrenal activity is associated with body weight gain and development of central adiposity in Pima Indian men.

To investigate the possible role of impaired sympathetic nervous system and/or adrenal medullary function in the etiology of human obesity, we studied 64 Pima Indian men (28 +/- 6 years, 101 +/- 25 kg, 34 +/- 9% body fat, mean +/- SD) in whom sympathoadrenal function was estimated at baseline by measurements of 24-hour urinary norepinephrine (NE) and epinephrine (Epi) excretion rates under weight-maintenance conditions. Body weight, body composition (hydrodensitometry), and body fat distribution (waist-to-thigh circumference ratio, W/T) were measured at baseline and follow-up. Follow-up data were available on 44 subjects who gained on average 8.4 +/- 9.5 kg over 3.3 +/- 2.1 years. In these subjects, baseline NE excretion rate, adjusted for its determinants (i.e., fat free mass, fat mass, and W/T), correlated negatively with bodyweight gain (r = -0.38; p = 0.009). Baseline Epi excretion rate correlated negatively with changes in W/T (r = -0.44; p = 0.003). In conclusion, our data show for the first time that a flow sympathetic nervous system activity is associated with body weight gain in humans. Also, a low activity of the adrenal medulla is associated with the development of central adiposity.

Adipose Tissue↗

Hyperinsulinemia as a possible etiology for the high prevalence of non insulin dependent diabetes in Mexican Americans.

The prevalence of non-insulin dependent diabetes mellitus (NIDDM) is higher in Mexican Americans (MAs) than in non-Hispanic whites (NHWs) even after adjustment for the former's greater overall and more centralized adiposity. We previously have shown that MAs are more hyperinsulinemic than NHWs even after adjustment for body mass index (BMI), waist-to-hip ratio (WHR), subscapular-to-triceps skinfold ratio, and glucose tolerance. We now confirm these findings in much larger population (n = 1,182). Since hepatic extraction of insulin may be decreased with upper body adiposity, we also measured fasting and 2-hour C-peptides in a subset of subjects (n = 70). C-peptide concentrations were higher in MAs than in NHWs indicating that MAs have higher insulin secretion. We examined whether the increased insulin concentrations in MAs may be associated with a bimodal distribution of insulin concentrations in which the second or higher mode might represent pre-diabetics. No evidence of bimodality, however, was apparent. The effect of overall adiposity (BMI) and upper body adiposity was similar in both Mexican Americans (a high risk population for NIDDM) and non-Hispanic whites (a low risk population for NIDDM). These data indicate that, like other populations at high risk for NIDDM such as Pima Indians in the U.S. Southwest and Micronesians in the South Pacific, Mexican Americans have more hyperinsulinemia than can be accounted for by their adiposity and body fat distribution. Prolonged insulin secretion (secondary to increased insulin resistance), is one possible explanation for this phenomenon which could lead to islet cells decomposition and eventual clinical diabetes.

Adult↗

Physiological effects of human growth hormone produced after hydrodynamic gene transfer of a plasmid vector containing the human ubiquitin promotor.

Human growth hormone (hGH) deficiency causes retarded growth and abnormalities in body fat distribution and abundance, muscle growth, and bone mineralization. While injection of recombinant hGH may reverse or ameliorate symptoms of deficiency, therapy aiming at in vivo synthesis of hGH is still of considerable clinical interest. Hydrodynamic injection of a simple plasmid vector containing a human ubiquitin promotor and the hGH gene were found to result in high and prolonged expression. Synthesis of hGH was achieved both in NOD/SCID mice and in three different inbred strains of immune competent mice. Although hGH antibodies were produced in immunocompetent mice, physiological effects of the protein were documented by increase in body weight, increased serum levels of insulin-like growth factor I and relative increased weight of the internal organs. Nonviral gene therapy may be regarded as a potential future way of reconstituting hGH expression in deficient individuals.

Animals↗

[Morphological and metabolic abnormalities related to antiretroviral therapy].

The long term use of antiretroviral therapy is associated with metabolic and morphological abnormalities named lipodystrophy. The understanding of its epidemiology is in progress. NRTIs and Pls are involved in the origin of these abnormalities. So, NRTIs inhibit mitochondrial gamma polymerase and induce body fat distribution disorders. PIs interfere with lipid metabolism, leading to hyperlipidaemia and insulin resistance symptomatology. The diagnosis is made by clinical (far wasting or accumulation, or mixed syndrome) and biological signs (hyperlipidaemia, hyperglycaemia, hyperlactacidaemia). Radiological exams can quantify morphological abnormalities. The management consists in drug substitution, diet and exercise, and corrective drugs. Plastic surgery can be useful.

Adipose Tissue↗

Risk factors for non-insulin-dependent diabetes mellitus.

UNLABELLED: RISK FACTORS AND PREDICTORS: The risk factors for non-insulin-dependent diabetes mellitus (NIDDM) include age, overall adiposity, an adverse body fat distribution, adverse glucose and insulin concentrations, insulin resistance and lack of physical exercise. The strongest predictors of NIDDM appear to be metabolic factors, including impaired glucose tolerance and insulin resistance. TREATMENT: Pharmacological agents that improve insulin sensitivity are being tested in multicenter clinical trials. In patients with a high risk of NIDDM, it seems prudent to avoid the use of pharmacologic agents that increase insulin resistance.

Adipose Tissue↗

Abdominal obesity and the risk of Barrett's esophagus.

BACKGROUND: The association between overweight/obesity and the risk of Barrett's esophagus (BE) is unclear. Further, the association between body fat distribution and the risk of BE is unknown. METHODS: We conducted a retrospective case-control study in patients who underwent endoscopy at a single large VA Medical Center between 2000 and 2003. Cases were patients with documented BE who had an abdominal CT scan within 1 yr of the endoscopy, whereas controls were patients without BE (with or without erosive esophagitis) who also had an abdominal CT scan. The surface areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated from CT scan images at level of intervertebral disc between L4 and L5, and body mass index (BMI) in kg/m2 at the time of endoscopy was also recorded. Cases and controls were compared in univariate and multivariable analyses. RESULTS: We identified 36 cases and 93 controls. There were no significant differences between cases and controls in age (mean 63 yr), gender (98% men), or race (71% white Caucasian). BMI was significantly greater in cases than controls (27 vs 24; p= 0.006). BMI >30 kg/m2 was associated with a greater risk of BE than lower BMI (odds ratio 4.0; 95% CI: 1.4-11.1, p= 0.008). VAT was approximately 1.5-fold greater in cases than controls (183 vs 115 cm2; p < 0.0001), whereas SAT was less different (248 vs 200 cm2; p= 0.03). We estimated that each 10-cm2 increase in VAT was associated with 9% increase in risk of BE. Interestingly, VAT remained independently associated with BE in the model that adjusted for BMI, and in that model, BMI was not significantly associated with BE. CONCLUSIONS: Obesity seems to be associated with an increased risk of BE. Abdominal visceral adiposity might mediate most of this risk.

Adipose Tissue↗