Effect of glucose ingestion on peripheral glucose metabolism in normal man

This study was designed to determine the forearm exchange of energetic substrates (glucose and free fatty acids) and the carbohydrate and lipid oxidation rates of normal individuals, in the postabsorptive state and after an oral glucose challenge. Seventeen healthy male volunteers were studied after an overnight fast (12-14 h) and during 3 hours after ingestion of 75 g of glucose. The forearm glucose uptake rate reached the maximum at 60 minutes (0.935 +/- 0.098 mg/100 ml of forearm.min), while 114.9 +/- 9.4 and 90.1 +/- 8.4 mg/100 ml of forearm were the total and incremental peripheral uptake of glucose in 3 hours of study, respectively. After the ingestion of 75 g of glucose, an increase in the oxidation rate of this hexose was observed, corresponding to an increment in the basal oxidation of 21.0 +/- 2.6 mg/100 ml of forearm in 3 hours. The arterial and venous plasma levels of free fatty acids decreased significantly after the glucose meal, associated with a decrease in the lipid oxidation rate. In conclusion, the results of this study showed that, in normal subjects after ingestion of 75 g of glucose, 30.3 +/- 2.1 g (40.4% of the ingested load) of this substrate were processed by the skeletal muscle in the body as a whole and 8.1 +/- 0.6 g were oxidized in this tissue during 3 hours.     

Sex-related differences in Japanese patients with peripheral arterial disease

Objective

The goal of the study was to examine possible sex-related differences in the clinical characteristics and risk factors in Japanese patients with peripheral arterial disease (PAD).

Methods

Sex-related differences in clinical profiles, risk factors and treatments were examined in 730 consecutive patients with PAD (148 women (20.3%) and 582 men (79.7%)).

Results

The mean age of the women was higher than that of the men (73.6 ± 11.2 vs. 70.9 ± 9.1 years old, p = 0.002) and the proportion of subjects aged ≥75 years old was also higher in women (P = 0.005). Women more frequently had critical limb ischemia (P < 0.001) and diabetes mellitus (P = 0.026), but less frequent smoking and alcohol intake, compared to men (P < 0.001). Total cholesterol (P < 0.001) and LDL cholesterol (P = 0.014) were higher in women. Fontaine stages were correlated with age, diabetes, cerebral infarction and women (p < 0.001). The prevalence of iliac artery lesions was higher in men (p < 0.001), whereas that for below the knee lesions was higher in women (p < 0.001). The number of affected below the knee arteries was also higher in women than in men (p < 0.001). The prevalence of medical treatment was higher in women (P = 0.009) and major amputation tended to be higher in women (p = 0.056).

Conclusions

Women had more severe symptomatic states and uncontrolled risk factors. The prevalence of iliac artery lesions was lower, but below the knee lesions were more severe in women.     

Sex-related differences in bone metabolism in osteoporosis observational study

Although the incidence is lower in men than women, osteoporosis remains a significant health issue in men as it may give rise to severe complications if not managed appropriately. As men and women show different biological and social backgrounds, we retrospectively evaluated the differences in the bone metabolism between men and women using bone biomarkers.Bone mineral density (BMD) was determined in all patients using dual-energy X-ray absorptiometry (DXA) and analyzing various bone biomarkers such as carboxyl-terminal collagen crosslinks (CTX), osteocalcin (OCT), and alkaline phosphatase (ALP). The CTX/OCT ratio was used to estimate the association between bone absorption and formation.OCT, CTX, and ALP levels were elevated in patients with osteoporosis. Women displayed a higher incidence of osteoporosis and greater reduction in BMD than men. The mean OCT level in men was lower than that in women. Moreover, men showed significantly lower OCT levels than women of aged 65 and under 80 years old. Among patients with osteoporosis, men had a higher ratio of bone markers than women.Levels of biomarkers of bone formation and absorption were increased in the osteoporosis group. However, men showed lower increases in bone formation biomarkers than did women, indicating that the rate of bone formation relative to bone absorption did not increase in men compared with that in women. Therefore, we suggest that men and women have different bone metabolism in old age.     

Insulin sensitivity: gender-related differences in subjects with normal glucose tolerance

BACKGROUND AND AIMS: To verify whether age and the perimenopausal state may herald the onset of the metabolic syndrome (MS) in females as compared to age-matched males, we studied subjects with normal glucose tolerance, according to ADA definition. METHODS AND RESULTS: In 368 eligible subjects subdivided into three age groups we measured insulin sensitivity by ISI-glycaemia, resistance by HOMA-IR, computed, during OGTT, from fasting and 2-h post-load plasma insulin and glucose concentrations. The significance of differences was tested between different age groups and between males and females within corresponding age groups. Insulin sensitivity fell slightly and insulin resistance rose significantly in the perimenopausal group as compared to younger and older female patients, and compared to men of the same age. This pattern remains after excluding patients with high blood pressure, and after adjusting for WHR and BMI by multivariate analysis. HOMA-IR averaged 2.9+/-1.8 in females, 2.2+/-1.2 in men aged 45-54 years (p<0.02), while in the other age groups insulin resistance was higher in men. CONCLUSION: The onset of MS during the menopause is associated with a physiological shift in insulin resistance occurring even in normal glucose tolerant subjects, suggesting that it may depend upon critical metabolic changes occurring specifically in that age period.     

Sex-related differences in the normal cardiac response to upright exercise

In previous studies from this laboratory, we found that approximately 30% of women with chest pain and normal coronary arteries demonstrated either a decrease in or a failure to increase radionuclide ejection fraction during exercise. To examine the hypothesis that this apparent abnormality in left ventricular function represents a physiologic difference between men and women, we prospectively studied central and peripheral cardiovascular responses to exercise in 31 age-matched healthy volunteers (16 women and 15 men). A combination of quantitative radionuclide angiography and expired-gas analysis was used to measure ejection fraction and relative changes in end-diastolic counts, stroke counts, count output, and arteriovenous oxygen difference during symptom-limited upright bicycle exercise. Normal male and female volunteers demonstrated comparable baseline left ventricular function and similar aerobic capacity, as determined by weight-adjusted peak oxygen consumption (22.1 +/- 5.1 and 22.6 +/- 4.3 ml/kg/min, respectively). However, their cardiac responses to exercise were significantly different. Ejection fraction increased from 0.62 +/- 0.09 at rest to 0.77 +/- 0.07 during exercise in men (p less than .001), but was unchanged from 0.63 +/- 0.09 at rest to 0.64 +/- 0.10 during exercise in women. The ejection fraction increased by 5 points or more in 14 of 15 men, but in only seven of the 16 women. End-diastolic counts increased by 30% in women (p less than .001), but was unchanged in men. Because decreases in ejection fraction were matched by increases in end-diastolic counts, relative increases in stroke counts and count output were the same for men and women. These data demonstrate a basic difference between men and women with respect to the mechanism by which they achieve a normal response of stroke volume to exercise; these differences must be taken into account when measurements of cardiac function during exercise stress are used for diagnostic purposes.     

Sex-related differences in hematological values

Summary Hematological data known or supposed to be influenced by individual sex hormones were evaluated in 18 untreated transsexuals (TS) and in 20 castrated or non-castrated TS on androgen and estrogen treatment, respectively. Profiting from a situation of clinically controlled hormonal sex-transformation it was tested, whether the circulating erythrocyte and granulocyte mass and iron metabolism are linked to a male and female sex-hormone constellation. The erythrocyte and granulocyte counts were significantly higher in untreated males and treated female-to-male TS than in untreated females and treated male-to-female TS. The unexpected finding of sex hormone-dependent granulocyte fluctuations was corroborated by parallel concentration changes of lactoferrin, a granulocytederived plasma protein. Iron metabolism as judged from plasma iron, total iron-binding capacity and serum ferritin was unaffected by sexual transformation. Plasma iron and the total iron-binding capacity did not differ significantly in untreated and treated TS of either type. The serum ferritin concentration, however, was significantly lower in untreated as well as in virilized females than in untreated and in feminized males, but was not significantly changed by long-term androgen or estrogen treatment. The present study demonstrates the potential of human transsexualism as a model for the study of sex-related biological processes.     

Sex-related differences in heart failure

Heart failure (HF) is a complex syndrome that is generally defined as cardiac output not adequate to meet the circulatory demands of the body. HF is at the end of the continuum of cardiovascular disease and preceded by an initiating event such as myocardial infarction, untreated hypertension, idiopathic cause, congenital heart disease, or pulmonary hypertension. In recent years, research has revealed differences in various aspects of HF between men and women including risk factors, pathophysiology, clinical manifestations, and response to treatment. Therefore, the purpose of this review is to review these sex-related differences between men and women who live with HF.     

Effect of 50 and 100 g glucose loads on peripheral muscle glucose metabolism in normal man.

The present study was designed to determine the effects of 50 and 100 g glucose loads on forearm muscle glucose uptake, oxidation and nonoxidative glucose metabolism in normal man. Ten healthy male subjects were studied during the postabsorptive state (12-14 h overnight fast) and for 3 hours following glucose ingestion. Peripheral glucose metabolism was analysed by the use of the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Greater forearm muscle uptake and nonoxidative metabolism of glucose were observed in the subjects during the G.100 study than during the G.50 study (G.100 = 178.9 +/- 19.7 and 155.3 +/- 23.0 vs 103.5 +/- 16.6 and 85.2 +/- 16.7 mg/100 g forearm muscle. 3 h, respectively). the muscle glucose oxidation did not show significant difference after the two glucose loads. Insulin levels reached after 100 g glucose ingestion were significantly higher than after the 50 g glucose load. In conclusion, this study revealed a dose-dependent metabolic response in the muscular tissue of normal subjects to oral glucose loads of 50 and 100 g, with respect to forearm muscle glucose uptake and nonoxidative glucose metabolism. The oxidative responses of the muscle tissue to the oral glucose challenges seem not to be directly proportional to the ingested meals.     

Sex-related naloxone influence on growth hormone-releasing hormone-induced growth hormone secretion in normal subjects

The effect of opiate-receptor antagonist naloxone on growth hormone (GH) release after growth hormone-releasing hormone (GHRH) 1-44 administration was investigated in ten normal men and 18 normal women during different phases of their menstrual cycle. Naloxone was infused at a rate of 1.6 mg/h in women and 1.6- and 3.2 mg/h in men, starting one hour before GHRH administration (50 micrograms iv as a bolus). On different day sessions, naloxone, GHRH, or saline were administered as controls. Naloxone infusion reduced the GHRH-induced GH release in normal women. The mean % inhibition of peak GH response was 83% during follicular phase, 46.5% during periovulatory phase, and 77.6% during luteal phase. On the contrary, in normal men, both doses of naloxone infusion were ineffective in blunting the GH response to GHRH. Our studies indicate that naloxone infusion was capable of inhibiting GH release induced by direct stimulation with GHRH in normal women, suggesting an opiate-antagonist action at the anterior pituitary level. The absence of such an effect in normal men strongly indicates a sex dependence of naloxone effects and suggests a role of the sexual steroid environment in opioid modulation of pituitary hormone secretion.     

Body surface area may explain sex differences in findings from the oral glucose tolerance test among subjects with normal glucose tolerance

Background and aimsCurrent guidelines on prediabetes and diabetes (T2D) recommend to regularly perform an oral glucose tolerance test (OGTT) on subjects at risk of T2D. However, it is not known why women tend to have relatively higher 2-h post-load plasma (2hPG) glucose concentrations during OGTT than men. The aim of the present study is to investigate if there are sex differences in fasting plasma glucose (FPG) and 2hPG concentrations in relation to body size in apparently healthy non-diabetic subjects with normal glucose tolerance. We hypothesized that sex differences in glucose tolerance are physiological and related to different body surface area (BSA) in men and women.Methods and resultsA 2-h 75 g OGTT was performed on 2010 subjects aged 45–70 years. Their BSA was calculated using the Mosteller formula. Men and women were separately divided into five BSA levels. Within the normal 2hPG range, women had higher mean 2hPG concentrations during the OGTT than men in all BSA levels estimated by sex-standardized BSA (p for linearity < 0.001). BSA adjusted for age, waist circumference, leisure-time physical activity, and smoking, showed an inverse association with 2hPG concentration in both sexes. Mean FPG concentrations were higher in men than in women.ConclusionsBody size has a negative inverse association with 2hPG concentration in an OGTT even within a physiological plasma glucose range. This may cause underestimation of glucose disorders in individuals with larger BSA and overestimation in individuals with smaller BSA when using an OGTT.     

Contribution of skeletal muscle mass on sex differences in 2-hour plasma glucose levels after oral glucose load in Thai subjects with normal glucose tolerance

Women have higher 2-hour plasma glucose levels after oral glucose challenge than men. The smaller skeletal muscle mass in women may contribute to the higher postload glucose levels. The objective of this study was to test the hypothesis that the different amount of skeletal muscle mass between men and women contributed to sex difference in postload plasma glucose levels in subjects with normal glucose tolerance. Forty-seven Thai subjects with normal glucose tolerance, 23 women and 24 age- and body mass index-matched men, were studied. Body fat, abdominal fat, and appendages lean mass were measured by dual-energy x-ray absorptiometry. Skeletal muscle insulin sensitivity was determined by euglycemic-hyperinsulinemic clamp. First-phase insulin secretion and hepatic insulin sensitivity were determined from oral glucose tolerance data. β-Cell function was estimated from the homeostasis model assessment of %B by the homeostasis model assessment 2 model. Correlation and linear regression analysis were performed to identify factors contributing to variances of postload 2-hour plasma glucose levels. This study showed that women had significantly higher 2-hour plasma glucose levels and smaller skeletal muscle mass than men. Measures of insulin secretion and insulin sensitivity were not different between men and women. Male sex (r = −0.360, P = .013) and appendages lean mass (r = −0.411, P = .004) were negatively correlated with 2-hour plasma glucose, whereas log 2-hour insulin (r = 0.571, P < .0001), total body fat (r = 0.348, P = .016), and log abdominal fat (r = 0.298, P = .042) were positively correlated with 2-hour plasma glucose. The correlation of 2-hour plasma glucose and sex disappeared after adjustment for appendages lean mass. By multivariate linear regression analysis, log 2-hour insulin (β = 18.9, P < .0001), log 30-minute insulin (β = −36.3, P = .001), appendages lean mass (β = −1.0 × 10⁻³, P = .018), and hepatic insulin sensitivity index (β = −17.3, P = .041) explained 54.2% of the variance of 2-hour plasma glucose. In conclusion, the higher postload 2-hour plasma glucose levels in women was not sex specific but was in part a result of the smaller skeletal muscle mass. The early insulin secretion, hepatic insulin sensitivity, and skeletal muscle mass were the significant factors negatively predicting 2-hour postload plasma glucose levels in Thai subjects with normal glucose tolerance.     

Glutamine and glucose metabolism in human peripheral lymphocytes

The metabolism of glutamine and glucose in resting and concanavalin A-stimulated human peripheral lymphocytes was investigated. Glutamine was metabolized at a high rate by resting and mitogen-stimulated human peripheral lymphocytes and the major end-products of glutamine metabolism were glutamate, aspartate, CO2, and ammonia: the carbon from glutamine may contribute about 21% to respiration. Concanavalin A enhanced the formation of all end-products except glutamate, indicating that more glutamine was metabolized beyond the stage of glutamate in the mitogen-stimulated cells. Mitogenic stimulation caused an increase in the rates of glucose utilization, lactate production and 14CO2 from variously labeled [14C] glucose. Concanavalin A caused an increase in the oxidation of pyruvate as indicated by the enhanced release of 14CO2 from [2-14C]-, [3,4-14C]-, and [6-14C]-glucose. When both glucose and glutamine were presented to the cells, the rates of utilization of both substrates increased and the increased rates of glucose and glutamine utilization could be accounted for mainly by increased rates of lactate and glutamate production, respectively.     

Pterin metabolism in normal subjects and hyperphenylalaninaemic patients

The application of high performance liquid chromatography to the estimation of urinary pterins is illustrated by results from normal subjects and from patients with phenylketonuria, dihydropteridine reductase deficiency and biopterin synthetase deficiency. In normal subjects following a phenylalanine load the is a temporary increase in pterin elimination, the pattern being different to that seen in chronic hyperphenylalaninaemia.     

Pterin metabolism in normal subjects and hyperphenylalaninaemic patients

The application of high performance liquid chromatography to the estimation of urinary pterins is illustrated by results from normal subjects and from patients with phenylketonuria, dihydropteridine reductase deficiency and biopterin synthetase deficiency. In normal subjects following a phenylalanine load there is a temporary increase in pterin elimination, the pattern being different to that seen in chronic hyperphenylalaninaemia.     

Sex-related differences in the insulin resistance syndrome

In the insulin resistance (IR) syndrome, sex-specific differences have been reported. First, hypertension more often correlates with hyperinsulinemia in women than in men with the IR syndrome. In addition, salt sensitivity of blood pressure appears to be independent of the activity of the renin-angiotensin system in women, whereas in men there is a strong correlation between the two variables. Secondly, the dyslipidemia found in women with the IR syndrome is characterized by less postprandial plasma insulin, triglycerides, and fatty acid response to a standardized meal. However, this sex difference in lipids disappears after correction for visceral fat mass. Fat physiology and biochemistry differ between the two sexes. In women, adipose cells express less glucocorticoid receptors and less 11β-hydroxysteroid dehydrogenase. In women visceral fat accumulation appears to be a constant feature of the IR syndrome but in men the syndrome can be present without central obesity. Lastly, during the reproductive years of women, the IR syndrome, such as in pre-eclampsia, may cause fetal growth retardation that has been proposed together with maternal malnutrition to be at the origin of the increased risk for impaired glucose tolerance, hyperinsulinemia, and hypertension in adult life. This gives yet another dimension to this disease in women since in essence they may ultimately transmit this syndrome to both sexes.     

Further evidence that insulin metabolism is a major determinant of peripheral insulin response to oral glucose in subjects with mild glucose intolerance

In mild glucose intolerance plasma concentration of C-peptide seems to give an estimate of pancreatic B cell secretion more reliable than plasma insulin itself. In the present study we measured the plasma levels of insulin and C-peptide after oral glucose load in 100 mildly glucose intolerant subjects, focusing our attention on high and low insulin responders. According to an insulin incremental area after oral glucose higher or lower than the mean +/- SD of the mean, 16 subjects were classified as "high insulin responders", and 17 as "low insulin responders". The two groups were similar for sex, age and bw. Mean insulin incremental area was almost 9-fold greater in high insulin responders than in low insulin responders (0.88 +/- 0.03 vs 0.10 +/- 0.01 pmol/ml min, p less than 0.001). Also mean C-peptide incremental area was significantly greater in high insulin responders than in low insulin responders, but the differences between the two groups were smaller. Indeed, mean C-peptide area was approximately 2.5-fold greater in high insulin responders than in low insulin responders (1.58 +/- 0.12 vs 0.66 +/- 0.07 pmol/ml min, p less than 0.001). These results give further support to the concept that in mild glucose intolerance insulin metabolism is a major determinant of peripheral insulin response to oral glucose load.     

北京地区360例糖耐量正常人五年后糖代谢状态再分析

本研究组曾于 1994年对北京地区部分人群进行了糖尿病筛查及对 15 66人行口服葡萄糖耐量试验 (ＯＧＴＴ) ,获得了有关北京地区糖尿病及糖耐量低减 (ＩＧＴ)患病率及其患病特点的数据〔1〕。在此基础上 ,于 1999至 2 0 0 0年对上述部分人群进行了 5年后随访。本研究选择其中 3 60例于 1994年经ＯＧＴＴ证实为糖耐量正常 (ＮＧＴ)者 ,探讨其 5年后糖代谢改变及影响因素。一、对象和方法1.对象 :本研究组于 1994年对北京地区进行了糖尿病筛查 ,抽样方法详见文献〔1〕。根据ＷＨＯ糖尿病诊断标准(1985年 ) ,经ＯＧＴＴ证实为ＮＧＴ者 85 8人。 5…