Serum leptin concentration,obesity, and insulin resistance in Western Samoans: cross sectional study.

OBJECTIVE: To measure serum leptin concentrations in the Polynesian population of Western Samoa and to examine epidemiological associations of leptin with anthropometric, demographic, behavioural, and metabolic factors in this population with a high prevalence of obesity and non-insulin dependent diabetes mellitus. DESIGN: Cross sectional study, leptin concentration being measured in a subgroup of a population based sample. SUBJECTS: 240 Polynesian men and women aged 28-74 years were selected to cover the full range of age, body mass index, and glucose tolerance. MAIN OUTCOME MEASUREMENTS: Serum leptin, insulin, and glucose concentrations; anthropometric measures; physical activity; and area of residence. RESULTS: Leptin concentrations were correlated with body mass index (r = 0.80 in men, 0.79 in women) and waist circumference (r = 0.82 in men, 0.78 in women) but less so with waist to hip ratio. At any body mass index, leptin concentration was higher in women than men (geometric mean adjusted for body mass index 15.3 v 3.6 pg/l, P < 0.001). Leptin concentration also correlated with fasting insulin concentration (r = 0.63 in men, 0.64 in women) and insulin concentration 2 hours after a glucose load (r = 0.58 in men, 0.52 in women). These associations remained significant after controlling for body mass index; effects of physical activity and of rural or urban living on leptin concentration were eliminated after adjusting for obesity, except values remained high in urban men. 78% of variance in leptin was explained by a model including fasting insulin concentration, sex, body mass index, and a body mass index by sex interaction term. Similar results were obtained if waist circumference replaced body mass index. CONCLUSIONS: The strong relation of leptin with obesity is consistent with leptin production being proportional of mass to adipose tissue. The relation with insulin independent of body mass index suggests a possible role for leptin in insulin resistance or hyperinsulinaemia.     

Obesity Modulates the Association among APOE Genotype,Insulin, and Glucose in Men

Objective: Obesity, insulin resistance, and apolipoprotein E (APOE) genotype have all been associated with coronary heart disease. We examined the interaction between obesity and APOE genotype in determining fasting insulin and glucose levels. Research Methods and Procedures: From 1991 to 1995, 3799 subjects underwent a clinical examination and fasting insulin and glucose measurement. APOE genotypes were determined on 3500 participants. Participants taking oral hypoglycemic drugs or insulin preparations or with the rare APOE2/4 genotype were excluded. Finally, 2929 individuals were included in the present analysis. Results: In men, we observed a statistically significant interaction between obesity and APOE genotype on insulin and glucose level (p = 0.003 and 0.008, respectively). Obese men with the APOE4 genotype presented with higher levels of insulin and glucose than obese men in the other genotype groups. No association between genotype and insulin or glucose in nonobese men was observed. Obesity was associated with higher insulin levels in the three APOE genotypes groups, whereas obesity was directly associated with glucose in those with the APOE4 genotype. In women, the effect of interaction between APOE genotype and obesity on fasting insulin and glucose was not statistically significant. Obesity was associated with higher levels of fasting insulin and glucose. APOE genotype was not associated with insulin or glucose. Discussion: Obesity modulates the association between the APOE genotype and fasting insulin and glucose levels in men. Although weight control is important in all people, it may be especially important in APOE4 men to modify potentially elevated fasting insulin and glucose levels.     

Dietary Patterns,Metabolic Markers and Subjective Sleep Measures in Resident Physicians

Shiftwork is common in medical training and is necessary for 24-h hospital coverage. Shiftwork poses difficulties not only because of the loss of actual sleep hours but also because it can affect other factors related to lifestyle, such as food intake, physical activity level, and, therefore, metabolic patterns. However, few studies have investigated the nutritional and metabolic profiles of medical personnel receiving training who are participating in shiftwork. The aim of the present study was to identify the possible negative effects of food intake, anthropometric variables, and metabolic and sleep patterns of resident physicians and establish the differences between genders. The study included 72 resident physicians (52 women and 20 men) who underwent the following assessments: nutritional assessment (3-day dietary recall evaluated by the Adapted Healthy Eating Index), anthropometric variables (height, weight, body mass index, and waist circumference), fasting metabolism (lipids, cortisol, high-sensitivity C-reactive protein [hs-CRP], glucose, and insulin), physical activity level (Baecke questionnaire), sleep quality (Pittsburgh Sleep Quality Index; PSQI), and sleepiness (Epworth Sleepiness Scale; ESS). We observed a high frequency of residents who were overweight or obese (65% for men and 21% for women; p?=?0.004). Men displayed significantly greater body mass index (BMI) values (p?=?0.002) and self-reported weight gain after the beginning of residency (p?=?0.008) than women. Poor diet was observed for both genders, including the low intake of vegetables and fruits and the high intake of sweets, saturated fat, cholesterol, and caffeine. The PSQI global scores indicated significant differences between genders (5.9 vs. 7.5 for women and men, respectively; p?=?0.01). Women had significantly higher mean high-density lipoprotein cholesterol (HDL-C; p?<?0.005), hs-CRP (p?=?0.04), and cortisol (p?=?0.009) values than men. The elevated prevalence of hypertriglyceridemia and abnormal values of low-density lipoprotein cholesterol (LDL-C; >100?mg/dL) were observed in most individuals. Higher than recommended hs-CRP levels were observed in 66% of the examined resident physicians. Based on current recommendations, a high prevalence of low sleep quality and excessive daytime sleepiness was identified. These observations indicate the need to monitor health status and develop actions to reassess the workload of medical residency and the need for permission to perform extra night shifts for medical residents to avoid worsening health problems in these individuals.     

Oral Glucose Tolerance and Related Factors in a Normal Population Sample—II. Interrelationship of Glycerides,Cholesterol, and other Factors with the Glucose and Insulin Response

The data available from the previous paper have been analysed to determine the interaction between the blood sugar and plasma insulin responses to oral glucose and a number of other biological variables. The total sugar and insulin responses were derived by calculating the total area and the incremental area under the curves.The blood sugar area was significantly correlated with age in both men and women, particularly the former. A striking degree of correlation was found in men between the level of fasting glycerides and the blood sugar area. There was a significant correlation also in women, but this was entirely due to the presence of the older, postmenopausal individuals. A lower degree of correlation was found in both sexes between fasting glycerides and the insulin area.Obesity, as defined by three interrelated factors—ponderal index, triceps fat-fold thickness, and arm girth —was significantly correlated with the insulin area (the association being stronger in the men) and with the blood sugar area only in men.The fasting cholesterol level was correlated with obesity in both sexes but with the blood sugar area and the insulin area only in men.     

The Activity of the Hypothalamic‐Pituitary‐Adrenal Axis and the Sympathetic Nervous System in Relation to Waist/Hip Circumference Ratio in Men

Objective: To investigate possible differences, between generally and abdominally obese men, in activity and regulation of the hypothalamic‐pituitary‐adrenal (HPA) axis and the sympathetic nervous system. Research Methods and Procedures: Fifty non‐diabetic, middle‐aged men were selected to obtain two groups with similar body mass index (BMI) but different waist/hip circumference ratio (WHR). Measurements were performed of the activity of the HPA axis and the sympathetic nervous system, as well as metabolic and endocrine variables. Results: Men with a high WHR, in comparisons with men with a low WHR, had higher insulin, glucose, and triglyceride values in the basal state and higher glucose and insulin after an oral glucose tolerance test. Men with high WHR had elevated diurnal adrenocorticotropic hormone (ACTH) values but similar cortisol values, except lower cortisol values in the morning. Diurnal growth hormone concentrations showed reduced peak size. Stimulation of the HPA axis with corticotropin‐releasing hormone (CRH) and laboratory stress showed no difference in ACTH values between groups, but cortisol values were lower in men with high WHR. In comparison with men with a low WHR, men with a high WHR had elevated pulse pressure and heart rate in the basal state and after challenges by CRH and laboratory stress. They also had increased urinary excretion of catecholamine metabolites. Discussion: These results suggest a mild dysregulation of the HPA axis, occurring with elevated WHR independent of the BMI. The results also indicate a central activation of the sympathetic nervous system, such as in the early phases of hypertension, correlating with insulin resistance.     

Differential contribution of indigenous men and women to the formation of an urban population in the Amazon region as revealed by mtDNA and Y-dNA

The human populations of the Brazilian Amazon were formed by interethnic crosses between Europeans, Africans, and Amerindians. The relative contribution of men and women of different ethnic groups was not homogeneous, since the social policies of the first three centuries of Brazilian colonization encouraged mating between European men and indigenous women and, later on, African women. In order to test this model based on historical data, we compared the relative contribution of the Y-DNA and mtDNA of Amerindian and non-Amerindian populations to the formation of the urban population of the town of Belém, in the Amazon region, on the basis of a C→T mutation at locus DYS199 present in 90% of the Amerindian Y-DNA and of five markers that define 99% of the mitochondrial sequences of Amerindians. The contribution of indigenous men to the formation of this population was less than 5%, whereas the contribution of indigenous women was estimated at more than 50% of the mitochondrial sequences of the same population. Thus, the present results demonstrate that the contribution of indigenous women to the formation of the Belém population was 10 times higher than the contribution of indigenous men, a genetic consequence of social behavior and attitudes of the past; our results also help clarify the process of integration of indigenous communities into the urban societies in Brazil and possibly in other countries. Am J Phys Anthropol 109:175–180, 1999. © 1999 Wiley-Liss, Inc.     

Relationships of plasma C-peptide and gender to the urinary excretion of inositols in older people.

PURPOSE: The urinary excretions of myo-inositol and D-chiro-inositol are elevated in diabetes, and have been suggested as possible markers or effectors of insulin action. The aim of the present study was to measure the urinary excretion of these compounds, and to assess possible relationships with the metabolic control of glucose, in older, non-diabetic men and women. SUBJECTS: 32 older (age range 54-71 yrs), moderately overweight (body mass index 29.1 +/- 0.4 kg/m2, mean +/- SEM), non-diabetic men (n = 17) and women (n = 15). METHODS: 75 g oral glucose tolerance testing was done the day after all subjects had consumed nutrient-defined menus for five days. Plasma samples were analyzed for the concentrations of glucose, insulin, and C-peptide, and the 180-minute area under the curve (AUC) for each of these compounds was calculated. Samples from 24-hour urine collections were analyzed for the concentrations of myo-inositol, D-chiro-inositol, L-chiro-inositol, and pinitol. RESULTS: The fasting glucose, insulin, and C-peptide, and the AUC for glucose and insulin, were not different between men and women. C-peptide AUC was greater in the men versus the women (p < 0.001). The median urinary excretions (micromol/g creatinine) of myo-inositol (p < 0.001), D-chiro-inositol (p < 0.001), L-chiro-inositol (p < 0.05), and pinitol (p < 0.001) were higher, and the myo-inositol:D-chiro-inositol ratio was lower (p < 0.001), in the men versus women. For all subjects combined, C-peptide AUC was positively correlated with the urinary excretion of each of the measured inositols, as well as the myo-inositol:D-chiro-inositol ratio. The correlations between C-peptide AUC and these inositols were strongly influenced by the co-linear relationship between C-peptide AUC and gender. CONCLUSIONS: Collectively, these data show that older, moderately overweight, non-diabetic men and women with gender-related differences in glucose-stimulated C-peptide AUC, an indirect indicator of insulin secretion, also display differences in the urinary excretion of myo-inositol, D-chiro-inositol, L-chiro-inositol, and pinitol. The gender-related difference in the myo-inositol:D-chiro-inositol ratio suggests that, while the urinary excretion of all of the inositols measured were higher in the men than the women, the difference was more pronounced for D-chiro-inositol.     

Insulin resistance induced by hydrocortisone is increased in patients with abdominal obesity

Glucocorticoids hypersensitivity may be involved in the development of abdominal obesity and insulin resistance. Eight normal weight and eight obese women received on two occasions a 3-h intravenous infusion of saline or hydrocortisone (HC) (1.5 microg x kg(-1) x min(-1)). Plasma cortisol, insulin, and glucose levels were measured every 30 min from time(-30) (min) (time(-30)) to time(240). Free fatty acids, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were measured at time(-30), time(180), and time(240). At time(240), subjects underwent an insulin tolerance test to obtain an index of insulin sensitivity (K(ITT)). Mean(30-240) cortisol level was similar in control and obese women after saline (74 +/- 16 vs. 75 +/- 20 microg/l) and HC (235 +/- 17 vs. 245 +/- 47 microg/l). The effect of HC on mean(180-240) insulin, mean(180-240) insulin resistance obtained by homeostasis model assessment (HOMA-IR), and K(ITT) was significant in obese (11.4 +/- 2.0 vs. 8.2 +/- 1.3 mU/l, P < 0.05; 2.37 +/- 0.5 vs. 1.64 +/- 0.3, P < 0.05; 2.81 +/- 0.9 vs. 3.32 +/- 1.02%/min, P < 0.05) but not in control women (3.9 +/- 0.6 vs. 2.8 +/- 0.5 mU/l; 0.78 +/- 0.1 vs. 0.49 +/- 0.1; 4.36 +/- 1.1 vs. 4.37 +/- 1.2%/min). In the whole population, the quantity of visceral fat, estimated by computerized tomography scan, was correlated with the increment of plasma insulin and HOMA-IR during HC infusion [Delta mean(30-240) insulin (r = 0.61, P < 0.05), Delta mean(30-240) HOMA-IR (r = 0.66, P < 0.01)]. The increase of PAI-1 between time(180) and time(240) after HC was higher in obese women (+25%) than in controls (+12%) (P < 0.05), whereas no differential effect between groups was observed for free fatty acids or adiponectin. A moderate hypercortisolism, equivalent to that induced by a mild stress, has more pronounced consequences on insulin sensitivity in abdominally obese women than in controls. These deleterious effects are correlated with the amount of visceral fat.     

Effect of low birth weight on adrenal steroids and carbohydrate metabolism in early adulthood

AIM: Data are inconsistent whether hyperinsulinemia might be associated with adrenal hyperandrogenism in young adults born with low birth weight (LBW). METHOD: We investigated the insulin and adrenal steroid production of 70 young LBW adults [33 women (birth weight: 1,795 +/- 435 g) and 37 men (birth weight: 1,832 +/- 337 g)]. Their results were compared to those of 30 controls (14 men, 16 women), born with normal weight. RESULTS: In LBW women, we measured higher basal DHEA (33.5 +/- 13.1 vs. 23.6 +/- 8.7 nmol/l, p < 0.05), DHEAS (8.0 +/- 2.3 vs. 6.3 +/- 2.1 micromol/l, p < 0.05), androstenedione (8.3 +/- 2.8 vs. 6.0 +/- 2.2 nmol/l, p < 0.05) and cortisol (0.25 +/- 0.07 vs. 0.20 +/- 0.07 micromol/l, p < 0.05) levels and higher insulin response during oral glucose tolerance test (log.AUCins: 2.62 +/- 0.06 vs. 2.57 +/- 0.03, p < 0.05). DHEA levels correlated with fasting insulin levels (r = 0.45, p < 0.01) and insulin response (r = 0.33, p < 0.05). In LBW men, higher cortisol (0.27 +/- 0.06 vs. 0.22 +/- 0.06 micromol/l, p < 0.01) and SHBG (18.4 +/- 10.4 vs. 12.7 +/- 5.9 nmol/l, p < 0.05) levels were found. CONCLUSIONS: Our results suggest that modest hypercortisolism is present in young LBW adults. While the endocrine sequel of hypercortisolism raised insulin response and hyperandrogenism is detectable in apparently healthy young LBW women, it is absent in young LBW men. This suggests that gender-dependent mechanisms might play a role in the development of insulin resistance in LBW adults.     

Hormonal profile and glucose tolerance in late pregnancy and postpartum

Oral glucose tolerance, plasma insulin and basal levels of glucagon, hGH, hPRL, hPL, TSH, T4, T3, thyroxine-binding globulin (TBG), cortisol, corticosteroid-binding globulin (CBG) and estriol were measured in 23 normal pregnant women in late gestation (31 +/- 0.4 weeks of pregnancy). Twelve of these subjects could be re-examined 14 +/- 2 weeks postpartum. Blood glucose was lower basal and after glucose load (100 g) in the pregnant group. Fasting plasma insulin and glucose-induced insulin release were higher in pregnancy. The insulinogenic index and the beta cell response were significantly greater antepartum, while peripheral insulin activity was unchanged. The insulin:glucagon ratio as well as TSH and hGH showed no significant differences between ante- and postpartum values. However, T4, T3, TBG, cortisol, CBG, estriol, hPRL and hPL were significantly higher during gestation than after delivery. T4:TBG and T3:TBG ratios were much lower antepartum, while the cortisol:CBG ratio was comparable ante- and postpartum. To our knowledge this is the first report in which such an extensive hormonal and metabolic analysis was performed in the same women ante- and postpartum. It could be shown that glucose tolerance is not worsened during pregnancy in healthy subjects. The higher gestational insulin values are discussed with respect to the various significant hormonal changes.     

Association of Total and Central Adiposity Measures with Fasting Insulin in a Biracial Population of Young Adults with Normal Glucose Tolerance: the CARDIA Study

SIDNEY, STEPHEN, CORA E. LEWIS, JAMES O. HILL, CHARLES P. QUESENBERRY, JR, ELIZABETH R. STAMM, ANN SCHERZINGER, KIMBERLY TOLAN, AND BRUCE ETTINGER. Association of total and central adiposity measures with fasting insulin in a biracial population of young adults with normal glucose tolerance: the CARDIA study. Obes Res. Objective: To determine the association of computed tomography (CT)-measured visceral adipose tissue (AT) and other measures of adiposity with fasting insulin in a biracial (African American and Caucasian) study population of young adults. Research Methods and Procedures: The study population consisted of 251 young adults with normal glucose tolerance (NGT), ages 28–40 years, who were volunteers from the Birmingham, Alabama, and Oakland, California centers of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Results: In regression models with total adiposity measures (body mass index or dual-energy X-ray absorptiometry-measured percent fat), visceral AT (measured as a cross-sectional area in cm²) was generally a stronger predictor of insulin than overall adiposity in all race/gender groups (partial correlation coefficients ranging from 0. 31 to 0. 47) except for black men, in whom the associations were nonsignificant. Partial correlation coefficients between waist circumference and insulin, controlling for percent fat, were nearly identical to those between visceral AT and insulin in women and in white men. Analyses performed on 2060 NGT CARDIA subjects who were not in this study of visceral AT showed significant correlations of waist circumference with insulin in all racelgender groups, including black men, and that black men in the visceral AT study group were significantly leaner than other black male CARDIA subjects. Discussion: We conclude that visceral AT was associated with fasting insulin in NGT participants in three of the four race/gender groups (black men excepted) and that waist circumference was a good surrogate for visceral AT in examining associations of central adiposity with fasting insulin.     

Aging influences the level and functions of fasting plasma ghrelin levels: the POWIRS-Study

OBJECTIVE: Ghrelin, known for its orexigenic activity, also have functions such as vasodilation and a growth hormone releasing action. It is uncertain whether these functions change with increasing age. This study aimed to determine whether ghrelin levels differ between young and older women with different levels of obesity; and secondly whether the associations of ghrelin with metabolic syndrome (MS) components, adipocytokines, coagulation factors, and cortisol change with increasing age. METHODS AND RESULTS: Caucasian women (N=107) were divided into young (19-29 years) and older groups (30-56 years). Fasting ghrelin, leptin, adiponectin, glucose, insulin, cortisol, fibrinogen and plasminogen activator inhibitor-1 (PAI-1) levels were determined. Blood pressure (BP), body mass index and waist circumferences were measured. Older lean women showed lower levels of ghrelin (p<0.05) than young lean women, with no differences regarding BP, obesity, lipids, adipokines or insulin resistance (IR). Ghrelin levels of older women remained constant with increasing obesity, but younger women showed significantly reduced ghrelin levels in obese groups. Only younger women showed significant correlations between ghrelin and leptin, adiponectin, fibrinogen and PAI-1 (adjusted for age, obesity and menstrual phase), whereas both age groups showed significant correlations with IR. In younger women factor analysis grouped ghrelin with coagulation factors and all MS components. In older women ghrelin was absent from the MS cluster, but was associated with lower BP, cortisol and IR. CONCLUSIONS: Ghrelin levels were not significantly elevated in lean older women, and did not change with increased obesity in older women--as were observed in younger women. The functions of ghrelin also seem to change with increased age since only in young women ghrelin was associated with obesity, coagulation factors and leptin.     

Overweight,Waist Circumference,Age, Gender,and Insulin Resistance as Risk Factors for Hyperleptinemia

Objective: To evaluate the influence of overweight, waist circumference, age, gender, and insulin resistance as risk factors for hyperleptinemia. Research Methods and Procedures: A cross‐sectional study was carried out in a population of 197 subjects: 59 men (21 aged <60 years and 38 aged ≥60 years) and 138 women (37 aged <60 years and 101 aged ≥60 years). The groups were stratified by overweight and normal weight. After a 12‐hour fasting period, we measured serum leptin and insulin levels with radioimmunoassay methods. We also measured serum glucose and lipid profile. The data were analyzed by means of comparative tests. A variance‐stabilizing transformation (natural logarithmic) was used to meet multiple linear regression, analysis of covariance, and logistic regression models. Results: The leptin serum levels were higher and statistically significant in young and older women than they were in men. We observed an interaction between gender and body mass index to explain the difference in leptin levels (p < 0.0001). Our study demonstrated an inverse relationship between leptin with age and high‐density lipoprotein cholesterol. In logistic regression analysis, the overweight × gender interaction and waist circumference have a statistically significant influence as independent variables on hyperleptinemia (overweight × gender odds ratio = 6.81; 95% confidence interval, 1.10 to 46.86; p < 0.05 and waist circumference odds ratio = 4.34; 95% confidence interval, 1.47 to 12.83; p = 0.001). Discussion: Women who were overweight or had a higher waist circumference (women ≥ 88 cm and men ≥ 102 cm) have a significantly higher risk of having hyperleptinemia. The increase in age as an isolated variable is not a risk factor for hyperleptinemia.     

Glucoregulatory hormones in man at high altitude

Concentrations of glucose, lactic acid, free fatty acid (FFA), insulin, cortisol and growth hormone (GH) in the blood were monitored in 15 euglycaemic men (sojourners, SJ) at sea level (SL) and while at altitudes of 3500 m and 5080 m, in acclimatised low landers (ALL) and in high altitude natives (HAN). In SJ, blood glucose and insulin concentrations showed a significant increase on the 3rd and 7th day after arrival at high altitude (HA), thereafter returning to sea level values and remaining the same during the entire period of their stay at 3500 m. Subsequently, on arrival at higher altitude (5080 m) the glucose concentrations again showed an increase over the preceding values and returned to SL values on day 41 while at 5080 m. A significant increase in cortisol concentrations was seen on day 3 after arrival at HA and the increased levels were maintained until day 21 at 3500 m. The cortisol concentrations on day 30 after arrival at 5080 m came down to SL values and remained unchanged thereafter. No appreciable change in GH and FFA was seen during the sojourn at HA. On the other hand, blood lactic acid concentration decreased significantly. There was no difference between the fasting glucose concentrations in ALL at 3500 m and in HAN at 3500 m and 4200 m compared to values of SJ at SL, whereas ALL at 4200 m had higher glucose values. Concentrations of plasma insulin and GH in ALL and HAN were higher than the values of SJ at SL, whereas cortisol values did not show any difference. These observations indicated that at HA the glucose values were high for the insulin concentration observed and might have been due to increased secretion of GH by the pituitary gland.     

Depression,changes in peripheral blood cell count,and changes in selected biochemical parameters related to lead concentration in whole blood (Pb-B) of women in the menopausal period

The aimThe aim of this study was to assess the severity of depression, vasomotor symptoms, changes in peripheral blood cell count, and selected biochemical parameters in relation to the concentration of lead in whole blood of women in the perimenopausal period.MethodsThe study sample consisted of 233 women from the general population of the West Pomeranian Province (Poland) in age between 44–65 years. The intensity of menopausal symptoms was examined using the Blatt-Kupperman Index, and the severity of depression using the Beck Depression Inventory. The following biochemical data were evaluated: concentrations of glucose, triglycerides, HDL, C-reactive protein, glycated haemoglobin, cortisol, insulin, blood cell count, and lead concentration in whole blood (Pb-B).ResultsA whole blood Pb concentration below 5 μg/dl was found in 55 subjects (23.61 %), in 142 women (60.94 %) it ranged from 5 to 10 μg/dl, while in 36 women (15.45 %) was higher than 10 μg/dl. There was a strong positive correlation between Pb concentration in the blood of the examined women and the severity of depressive symptoms (Rs=+0.60, p = 0.001). The lowest mean values for total leukocytes (5.07 ± 1.22 thousand/μl) and neutrophils (2.76 ± 0.86 thousand/μl) were found in women with Pb concentration above 10 μg/dl (p < 0.05). There was a significant negative correlation between the number of total leukocytes (r=-0.45, p = 0.002) and neutrophils (r=-0.50, p = 0.001) and blood Pb concentration. Analysis showed statistically significant differences in glucose concentration (p < 0.05) between groups. Blood glucose was higher in women with Pb-B <5 and between 5−10 μg/dl than in women with Pb-B >10 μg/dl.ConclusionExposure to Pb may be a factor playing a significant role in the development of depressive symptoms in menopausal women. It may also be associated with glucose metabolism disorders and immunosuppression in women during this period of life.     

Leptin responses to physical inactivity induced by simulated weightlessness

Physical inactivity induced by head-down bed rest (HDBR) affects body composition (BC). Leptin is involved in BC regulation by acting on fuel homeostasis. We investigated whether leptin and counterregulatory hormone levels are affected by a 7-day HDBR. Fasting blood was sampled daily (0700) in males (n = 8) and on alternating days in females (n = 8) for measurements of leptin, insulin, norepinephrine (NE), epinephrine (Epi), growth hormone (GH), cortisol, nonesterified fatty acid (NEFA), and glucose. BC was measured by H(2)(18)O dilution. Energy intake (men 10.5 +/- 0.2 MJ/day, women 7.9 +/- 0.3 MJ/day) and BC were unchanged by HDBR. Increased levels of leptin (men 40%, P = 0.003; women 20%, P = 0. 050), insulin (men 34%, P = 0.018; women 25%, P = 0.022), and the insulin-to-glucose ratio (men 30%, P = 0.049; women 25%, P = 0.031) were noted. GH, NE, Epi, and cortisol levels were unaltered. NEFA dropped in both sexes, but glucose decreased only in women. In conclusion, HDBR increased leptin levels independently of stress response, changes in fat mass, energy intake, or gender. These changes were correlated to the insulin-resistance development in men. Further analyses are required, but the results have to be considered for longer HDBR periods with 1) the well-described drop in energy intake and 2) the BC changes.     

Contribution of the lean body mass to insulin resistance in postmenopausal women with visceral obesity: a Monet study

Some insulin-resistant obese postmenopausal (PM) women are characterized by an android body fat distribution type and higher levels of lean body mass (LBM) compared to insulin-sensitive obese PM women. This study investigates the independent contribution of LBM to the detrimental effect of visceral fat (VF) levels on the metabolic profile. One hundred and three PM women (age: 58.0+/-4.9 years) were studied and categorized in four groups on the basis of their VF (higher vs. lower) and lean BMI (LBMI=LBM (kg)/height (m2); higher vs. lower). Measures included: fasting lipids, glucose homeostasis (by euglycemic/hyperinsulinemic clamp technique and 2-h oral glucose tolerance test (OGTT)), C-reactive protein (CRP) levels, fat distribution (by computed tomography (CT) scan), and body composition (by dual-energy X-ray absorptiometry). Women in the higher VF/higher LBMI group had lower glucose disposal and higher plasma insulin levels compared to the other groups. They also had higher plasma CRP levels than the women in the lower VF/lower LBMI group. VF was independently associated with insulin levels, measures of glucose disposal, and CRP levels (P<0.05). LBMI was also independently associated with insulin levels, glucose disposal, and CRP levels (P<0.05). Finally, significant interactions were observed between LBMI and VF levels for insulin levels during the OGTT and measures of glucose disposal (P<0.05). In conclusion, VF and LBMI are both independently associated with alterations in glucose homeostasis and CRP levels. The contribution of VF to insulin resistance seems to be exacerbated by increased LBM in PM women.     

Association between urinary calcium excretion level and mortality in inhabitants of the Jinzu River basin area of Japan

A follow-up study on 5442 inhabitants (2699 men, 2743 women) was conducted to determine the association between urinary Ca excretion level and mortality of the general population of three different areas of the Jinzu River basin area, namely, non-Jinzu River, mixed, and the Jinzu River water systems, over a period of 6127 d. More than 98% of the subjects were followed completely in each area. In comparison with the low- and high-Ca-excretion groups (cutoff values; 25.1 mg/dL in men, 20.4 mg/dL in women), the mortality rates per 1000 person-years and standardized mortality ratios (SMRs) tended to be greater in the low-Ca-excretion groups than in the high-Ca-excretion groups in both sexes for each of the three areas. Moreover, Cox’s hazard ratios in men and women of the three areas exhibited negative values, 0.99 except for men of the mixed water system. These values were statistically significant in both sexes for the Jinzu River water system and in women for the non-Jinzu River water system. We conclude that the life-span becomes shorter as urinary Ca excretion levels become lower.     

Obesity, insulin resistance, and skeletal muscle nitric oxide synthase

The molecular mechanisms responsible for impaired insulin action have yet to be fully identified. Rodent models demonstrate a strong relationship between insulin resistance and an elevation in skeletal muscle inducible nitric oxide synthase (iNOS) expression; the purpose of this investigation was to explore this potential relationship in humans. Sedentary men and women were recruited to participate (means ± SE: nonobese, body mass index = 25.5 ± 0.3 kg/m(2), n = 13; obese, body mass index = 36.6 ± 0.4 kg/m(2), n = 14). Insulin sensitivity was measured using an intravenous glucose tolerance test with the subsequent modeling of an insulin sensitivity index (S(I)). Skeletal muscle was obtained from the vastus lateralis, and iNOS, endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) content were determined by Western blot. S(I) was significantly lower in the obese compared with the nonobese group (～43%; P < 0.05), yet skeletal muscle iNOS protein expression was not different between nonobese and obese groups. Skeletal muscle eNOS protein was significantly higher in the nonobese than the obese group, and skeletal muscle nNOS protein tended to be higher (P = 0.054) in the obese compared with the nonobese group. Alternative analysis based on S(I) (high and low tertile) indicated that the most insulin-resistant group did not have significantly more skeletal muscle iNOS protein than the most insulin-sensitive group. In conclusion, human insulin resistance does not appear to be associated with an elevation in skeletal muscle iNOS protein in middle-aged individuals under fasting conditions.     

Insulin sensitivity regulates cholesterol metabolism to a greater extent than obesity: lessons from the METSIM Study

Cholesterol synthesis is upregulated and absorption downregulated in insulin resistance and in type 2 dia-betes. We investigated whether alterations in cholesterol metabolism are observed across the glucose tolerance status, from normoglycemia through impaired glucose tolerance to type 2 diabetes, in 781 randomly selected men 45 to 70 years of age from a population-based Metabolic Syndrome in Men Study. Cholesterol metabolism was assayed using surrogate serum markers, squalene, and noncholesterol sterols. The study population was classified into subgroups according to glucose tolerance as follows: normoglycemia, impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes. LDL cholesterol did not differ between the groups. Cholesterol synthesis markers were lowest and absorption markers highest in normoglycemia. Sitosterol was lower in subjects with impaired fasting glucose compared with normoglycemic subjects (113 ± 7 vs. 136 ± 3 10² μmol/mmol of cholesterol, P < 0.05). LDL cholesterol was not associated with lathosterol/sitosterol ratio, a marker of cholesterol metabolism. Peripheral insulin sensitivity evaluated by the Matsuda index was associated with the lathosterol/sitosterol ratio in the entire population (r = −0.457, P < 0.001) and with that of lathosterol/cholestanol independently of obesity. In conclusion, cholesterol metabolism was altered already from subjects with impaired fasting glucose. Upregulated cholesterol synthesis was associated with peripheral insulin resistance independent of obesity.