Interactive effect of an acute bout of resistance exercise and dehydroepiandrosterone administration on glucose tolerance and serum lipids in middle-aged women

The present study determined the interactive effect of an acute bout of resistance exercise and dehydroepiandrosterone (DHEA) administration on glucose tolerance and serum lipids. Twenty middle-aged female subjects performed an acute bout of resistance exercise and were subsequently divided into two groups: placebo (age 40.7 +/- 2.0) and DHEA administered (age 39.0 +/- 2.7). Ten subjects who received DHEA (age 41.5 +/- 4.6) participated in a non-exercise control. DHEA (25 mg twice daily) or placebo was orally supplemented for 48 hours. Before exercise and 48 hours after the last exercise bout (14 hours after the last DHEA intake), an oral glucose tolerance test and an insulin concentration were determined. Levels of fasting serum cholesterol and triglyceride, tumor necrosis factor-alpha (TNF-alpha), creatine kinase (CK) were also measured. The DHEA administration significantly elevated the fasting dehydroepiandrosterone sulfate (DHEA-S) level by approximately 3-fold. Both acute resistance exercise and DHEA administration improved glucose tolerance, but no addictive effect was found. Furthermore, exercise and DHEA administration did not affect serum triglyceride and cholesterol levels, but both lipids were significantly lowered when DHEA was given following exercise. Resistance exercise induced elevations in serum CK and TNFalpha levels, but these increases were attenuated by the DHEA administration. The new finding of this study was that post-exercise DHEA administration decreased serum triglycerides and cholesterol. This effect appeared to be associated with its TNF-alpha lowering action.     

Positive effects of DHEA therapy on insulin resistance and lipids in men with angiographically verified coronary heart disease--preliminary study

OBJECTIVES: The aim of this study was to analyze the influence of DHEA therapy on insulin resistance (FIRI, FG/FI) and serum lipids in men with angiographically verified coronary heart disease (CHD). MATERIAL AND METHODS: The study included thirty men aged 41-60 years (mean age 52+/-0.90 yr) with serum DHEA-S concentration<2000 microg/l, who were randomized into a double-blind, placebo-controlled, cross-over trial. Subjects completed the 80 days study of 40 days of 150 mg oral DHEA daily or placebo, and next groups were changed after 30 days of wash-out. Fasting early morning blood samples were obtained at baseline and after each treatment to determine serum hormones levels (testosterone, DHEA-S, LH, FSH estradiol and IGF-1) and also metabolic profile (total cholesterol, LDL-cholesterol, triglicerides, HDL-cholesterol, insulin, glucose, fasting insulin resistance index--FIRI and FG/FI ratio). RESULTS: Administration of DHEA was associated with 4.5-fold increase in DHEA-S levels. Relative to baseline DHEA administration resulted in a decrease in insulin levels by 40% (p<0.005) and fasting insulin resistance index (FIRI) by 47% (p<0.004). Also total cholesterol levels and LDL-cholesterol levels decreased significantly (from 222.9+/-6.6 mg/dL to 207.4+/-6.6 mg/dL and from 143.9+/-6.9 mg/dL to 130.5+/-6.0 mg/dL respectively; p<0.05). Glucose levels dropped significant below baseline values after DHEA (p<0.001). Estrogen levels significantly increased after DHEA (p<0.05). While changes of serum concentrations of testosterone, LH, FSH, IGF-I, HDL-cholesterol, triglycerides were not statistical significant. Tolerance of the treatment was good and no adverse effects were observed. CONCLUSIONS: DHEA therapy in dose of 150 mg daily during 40 days in men with DHEA levels<2000 microg/l decreased total cholesterol concentration, insulin and glucose levels and fasting insulin resistance index (FIRI). This therapy may be a beneficial against CHD risk factors.     

Associations of iron status with breast cancer risk factors in adult women: Findings from National Health and Nutrition Examination Survey 2017–2018

ObjectiveThis study examined the association between iron status and a set of breast cancer risk factors among U.S. adult women aged 20–80 years.MethodsData from National Health and Nutrition Examination Survey (2017–2018) were used to examine the relation between serum ferritin, serum iron and transferrin saturation with a set of breast cancer risk factors [body mass index (BMI), waist circumference, glycosylated hemoglobin (HbA1c), fasting plasma glucose, insulin and HOMA-IR]. The multivariable linear regressions were used controlling for age, race/ethnicity, menopause status, education level, smoking status, alcohol consumption, physical activity, high-sensitivity C-reactive protein (hsCRP) and total energy intake.ResultsHbA1c, BMI and waist circumference data were available for 1902 women with a fasting sample (n = 913) for fasting plasma glucose, insulin and HOMA-IR. Transferrin saturation had significant, inverse associations with BMI, waist circumference and HbA1c. The size of difference observed were that participants in the fourth quartile of transferrin saturation had a 4.50 kg/m² smaller BMI, a 9.36 cm smaller waist circumference and a 0.1 % lower HbA1c level than participants in the first quartile. Similarly, serum iron concentrations were inversely associated with BMI and waist circumference. In addition, serum iron had significant, inverse associations with insulin and HOMA-IR. Sensitivity analyses among men gave similar results. For serum ferritin, there was a trend towards a positive association between waist circumference, HbA1c and fasting plasma glucose with serum ferritin. However, the associations did not reach statistical significance among women.ConclusionsIron status may impact breast cancer risk via effects on adiposity or glucose metabolism. The findings should be confirmed with further prospective data.     

Insulin secretion and sensitivity in hyperthyroidism

To examine the effect of hyperthyroidism on carbohydrate metabolism, we studied glucose-stimulated insulin secretion and glucose utilization in 8 subjects with Graves' disease before and after treatment for hyperthyroidism and 8 age-, sex- and weight-matched normal subjects. Subjects with Graves' disease had significant elevated serum levels of thyroxine (24.81 +/- 2.44 micrograms/dl, mean +/- SEM) and triiodothyronine (459 +/- 5.5 ng/dl, mean +/- SEM). Simultaneous measurement of plasma glucose, serum insulin and C-peptide levels during fasting and every 30 minutes up to 180 minutes after 75 g oral glucose loading was determined. In addition, plasma glucose, serum insulin and serum C-peptide were measured during euglycemic glucose clamp with insulin infusion of 40 mU/m2 min-1. Mean fasting plasma glucose (P less than 0.05, serum insulin (P less than 0.005) and serum C-peptide (P less than 0.005) levels were significantly higher in the hyperthyroid patients. After glucose loading, the plasma glucose (P less than 0.05), serum insulin (P less than 0.05) and C-peptide (P less than 0.05) responses were significantly higher in hyperthyroid patients at all times up to 180 minutes. During euglycemic clamp studies, the steady-state serum insulin levels were identical in the two groups. The glucose disposal rate was lower in hyperthyroid patients before treatment (P less than 0.01) than in normal subjects. After thyroid function had been normalized for 2 to 4 weeks, the glucose disposal rate increased significantly (P less than 0.05), but was still significantly lower than those of normal subjects (P less than 0.05). Our data show that patients with Graves' hyperthyroidism manifest glucose intolerance, hyperinsulinemia and insulin resistance.     

The relationship between testosterone and dehydroepiandrosterone sulfate concentrations, insulin resistance and visceral obesity in elderly men

INTRODUCTION: Sex hormones deficiency--hypotestosteronemia (20-30% of men) and dehydroepian-drosterone sulfate deficiency (60-70% of men) are often observed in elderly men. In these men also changes of body composition (visceral obesity, increasing of fat mass), and metabolic disturbances (hypercholesterolemia, hyperinsulinism and insulin resistance) are common disorders. Visceral obesity and insulin resistance may be either reasons or effects of testosterone deficiency. Probably also DHEA-S deficiency is the risk factor of visceral obesity and insulin resistance, but it is not clear, whether this possible influence is independent from testosterone deficiency. OBJECTIVES: The aim of this study was to analyze the association between testosterone and DHEA deficiency and waist/hip ratio (WHR), levels of glucose and insulin resistance (HOMA and FG/FI) in elderly men as well as analysis, whether these sex hormones influent on measured parameters separately. MATERIAL AND METHODS: Together 85 men with age from 60 to 70 years men (mean 66.3+/-1.5 years; mean+/-SEM) was analyzed. Testosterone levels<4 ng/ml or DHEA levels<2000 ng/ml and BMI<30 kg/m2 were including criteria. Patients were divided into three groups: 52 with testosterone deficiency (L-T), 32 with DHEA deficiency (L-DHEA-S) and 67 with deficiency of both sex hormones (L-T/DHEA-S). Statistical analysis was made using Student-t, Kruskal-Wallis, and Mann-Whitney tests. RESULTS: Testosterone levels in L-T, L-DHEA and L-T/DHEA groups were respectively 3.19+/-0.23 ng/ml, 4.89+/-0.45 ng/ml and 3.25+/-0.34 g/ml (p<0.002). While DHEA-S levels were respectively 2498+/-98 ng/ml, 1435+/-1010 ng/ml and 1501+/-89 ng/ml). BMI values do not differ between groups. WHR ratio values were the highest in L-T/DHEA-S group (p<0.05 vs. L-T) group, significant lower in L-T group (p<0.005 vs. L-DHEA-S) and the lowest in L-DHEA-S group. Insulin fasting levels were lowest in L-DHEA-S group, higher in L-T group (p<0.01) and the highest in L-T/DHEA-S group (p<0.001 vs, L-T group). FG/FI values were the highest in L-DHEA-S group, lower in L-T group (NS) and lowest in L-T/DHEA group (p<0.002 vs. L-T group). HOMA ratio values similarly did not change significantly between L-T (6.6+/-3.21) and L-DHEA-S group (5.5+/-2.92), although tendency to higher values in L-T group was noticed, while WHR ratio values were significantly higher in L-T/DHEA group (7.3+/-2.45; p<0.002 vs. L-T group). CONCLUSIONS: DHEA-S and testosterone deficiency were independently associated with higher insulin resistance and obesity. WHR ratio seems to be more sensitive then BMI ratio to reflect the androgen deficiency on obesity and body composition in elderly men.     

Beta cell response to a mixed meal in nigerian patients with type 2 diabetes

ABSTRACT: BACKGROUND: The pathophysiology of type2 diabetes involves both insulin resistance and poor beta cell function. Studies have been done in several populations to assess the relative importance of these mechanisms in individual patients. In our environment studies to assess beta cell function have been done with glucagon stimulation or an oral glucose tolerance test. This study was done to assess the response of the beta cell to a standardized mixed meal and its relationship with glycaemic control in patients with type2 diabetes. METHODS: Ninety patients with type 2 diabetes were recruited into the study. Weight, height, body mass index and waist circumference were measured. Blood samples were analysed for fasting plasma glucose (FPG) and fasting C peptide (FCP) and glycated haemoglobin (HbA1c). Patients were given their usual drugs for management of their diabetes and then served with a standard meal calculated to contain 50 g of carbohydrate, made up of 53 % carbohydrate, 17 % of protein and 30 % of lipids, providing 500 kcal. Blood samples 2 hours after the start of the meal were analysed for postprandial glucose (PPG) and postprandial C peptide (PCP). Fasting (M0) and postprandial beta cell responsiveness (M1) were calculated. RESULTS: The mean FPG and PPG were 7.51+/ 3.39 mmol/l and 11.02+/4.03 mmol/l respectively while the mean glycated haemoglobin (HbA1c) was 9.0+/2.5 %. The mean fasting C peptide was 1.44+/1.80ug/ml. Many of the patients (56.7 %) had low FCP levels. The mean postprandial C peptide was 4.0+/2.8 ng/ml. There were significant correlations between M1, HbA1c and PPG (p = 0.015, 0.024, 0.001 respectively) and also between M0, HbA1c, PPG and FPG (p = 0.001, 0.002, 0.001). HbA1c decreased across increasing tertiles of M0 (p < 0.001) and also M1 (p = 0.002). In step-wise linear regression analysis, M0 and M1 significantly predicted HbA1c. CONCLUSIONS: Many of the patients had low C peptide levels with poor beta cell response to the meal. The patients had poor glycaemic control and poor beta cell function. Both fasting and postprandial beta cell responsiveness were significant determinants of blood glucose and glycated haemoglobin levels. It is likely that putting these patients on insulin may have led to better glycaemic control in them.     

Dehydroepiandrosterone therapy in men with angiographically verified coronary heart disease: the effects on plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and fibrinogen plasma concentrations

INTRODUCTION: The aim of this study was to analyze the influence of DHEA therapy on fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) plasma concentrations in men with decreased serum DHEA-S levels and angiographically verified coronary heart disease (CHD). MATERIAL AND METHODS: The study included thirty men aged 41-60 years (mean age 52 +/- 0.90 yr) with serum DHEA-S concentration < 2000 mg/l, who were randomized into a double-blind, placebo-controlled, cross-over trial. Subjects completed the 80 days study of 40 days of 150 mg oral DHEA daily or placebo, and next groups were changed after 30 days of wash-out. Fasting early morning blood samples were obtained at baseline and after each treatment to determine serum hormones levels (testosterone, DHEA-S, LH, FSH and estradiol) and also fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) plasma concentrations. RESULTS: Administration of DHEA was associated with 4.5-fold increase in DHEA-S levels. Estrogen levels significantly increased after DHEA from 22.1 +/- 0.7 pg/ml to 26.4 +/- 1.6 pg/l (mean +/- SEM; p < 0.05), while testosterone levels did not changed. Fibrinogen concentrations significantly decreased in DHEA group from 4.5 +/- 0.3 g/l to 3.83 +/- 0.2 g/l (p < 0.05 vs. placebo). Changes of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were not statistical significant (respectively: 8.37 +/- 0.4 ng/ml vs. 8.93 +/- 0.5 ng/ml and 82.3 +/- 6.3 ng/ml vs. 92.7 +/- 9.1 ng/ml (mean +/- SEM; NS vs. placebo). Tolerance of the treatment was good and no adverse effects were observed. CONCLUSIONS: DHEA therapy in dose of 150 mg daily during 40 days in men with DHEAS levels < 2000 mg/l and angiographically verified coronary heart disease (CHD) was connected with significant decreasing of fibrinogen concentration and increasing of estradiol levels, and did not influence on plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) plasma concentrations.     

Dehydroepiandrosterone in relation to adiposity, glucose tolerance and lipid spectra in Czech non-diabetic population

This study aimed to examine relationships between DHEA(S), anthropometric parameters, oral glucose tolerance test derived data and lipid spectra in a Czech non-diabetic population. 380 healthy volunteers both with and without a family history of diabetes type 2 (DM2) were enrolled into the study (women: n=235, age 28.9+/-9.4 years, BMI 22.3+/-4.5 kg/m(2), men: n=145, age 32.3+/-10.0 years, BMI 24.7+/-3.6 kg/m(2)). Spearman's correlations (both without and with the adjustment for age, age and BMI), as well as ANCOVA were used. Non-adjusted data showed many "beneficial" correlations between DHEA(S) and both anthropometric and metabolic variables. Statistical analysis revealed that almost all correlations of DHEA(S) to adiposity and fat distribution in men as well as in women disappeared after the adjustment. There are, however, differences between men and women in the correlation of DHEA(S) to insulin sensitivity and lipid levels. The use of hormonal contraceptives (COC) is also an important factor in this relationship. In men and also in women using COC, DHEA-S after adjustment correlated positively with fasting and stimulated glucose, insulin and C-peptide, and negatively with insulin sensitivity. In this respect, the benefit of DHEA(S) supplementation seems -- at least in terms of its alleged antiobesity and antidiabetogenic effects -- to be more than controversial.     

The relationship between androgens concentrations (testosterone and dehydroepiandrosterone sulfate) and metabolic syndrome in non-obese elderly men

INTRODUCTION: The metabolic syndrome characterized by central obesity, insulin and lipid dysregulation, and hypertension, is a precursor state for atherosclerotic process and, in consequence, cardiovascular disease. Decline of both testicular and adrenal function with aging causes a decrease in androgen concentration in men. It has been postulated that low levels of total testosterone and dehydroepiandrosterone sulfate (DHEA-S) are associated with unfavorable levels of several strong cardiovascular disease risk factors, such as lipids and blood pleasure, which are components of the metabolic syndrome, and insulin levels. Both testosterone and DHEA-S deficiency are risk factors of obesity and insulin resistance, but it is not clear, whether this possible influence is independent. The aim of this study was to determined whether lower androgens (testosterone and DHEA-S) levels are associated with the development of metabolic syndrome in non-obese elderly men as well as analysis, whether these sex hormones influents on measured parameters separately. MATERIAL AND METHODS: Together 85 men age from 60 to 70 years (mean 66.3 +/- 1.5 years; mean +/- SEM) were analyzed. Testosterone levels < 4 ng/ml or DHEA levels < 2000 ng/ml and BMI < 30 kg/m(2) were including criteria. Patients were divided into three groups: 52 with testosterone deficiency (L-T), 32 with DHEA deficiency (L-DHEA-S) and 67 with deficiency of both sex hormones (L-T/DHEA-S). The influence of sex hormones deficiency in these groups on blood pressure, lipids, visceral obesity and fasting glucose were measured (according to metabolic syndrome definition NCEP III/IDF). RESULTS: Testosterone levels in L-T, L-DHEA and L-T/DHEA-S groups were respectively 3.19 +/- 0.23 ng/ml, 4.89 +/- 0.45 ng/ml and 3.25 +/- 0.34 g/ml (p < 0.002). While DHEA-S levels were respectively 2498 +/- 98 ng/ml, 1435 +/- 1010 ng/ml and 1501 +/- +/- 89 ng/ml). BMI values do not differ between groups. Waist circumference was significantly higher in L-T/DHEA-S group than in L-T i L-DHEA-S groups (respectively: 99.9 +/- 6,1 cm, 97.1 +/- 7.1 cm i 96.2 +/- 6.4 cm; mean +/- SD, p < 0.05 vs. L-T and L-DHEA-S groups). Mean triglycerides concentration in L-T/DHEA-S group was significantly higher than in L-T and L-DHEA-S groups (respectively: 188.2 +/- 13.3 mg/dl, 161.7 +/- 14.7 mg/dl and 152.2 +/- 12.8 mg/dl (mean +/- SD; p < 0.02 vs. L-T and L-DHEA-S groups). Analysis of prevalence of risk factors showed, that in L-T/DHEA-S group they were more frequent than in other groups. The most significant percentage difference was observed for triglycerides: concentration > or = 150 mg/dl was measured in 31% men in L-T group, 28% men in L-DHEA-S group and 42% men in L-T/DHEA-S group. According metabolic syndrome definition NCEP III/IDF prevalence of this syndrome was: 71% patients in L-T/DHEA-S group, 67% patients in L-T group and 64% patients in L-DHEA-S group. CONCLUSIONS: The DHEA-S and testosterone deficiency was a significant and independent risk factor of the metabolic syndrome in non-obese elderly men. It seems, that triglycerides concentration and waist circumference are more sensitive then others parameters to reflect the influence of sex hormones deficiency on risk of the metabolic syndrome in elderly men.     

妊娠糖尿病患者血清HbA1c与CRP水平的相关性分析

目的:为明确妊娠期糖尿病(gestational diabetes mellitus,GDM)患者血清糖化血红蛋白(glycosylated hemoglobin,Hb A1c)与C反应蛋白(C-reactive protein,CRP)的关系,本研究检测了GDM患者血糖、血清Hb A1c与CRP水平,并对Hb A1c与CRP的相关性进行了分析。方法:以68例2015年4月至2017年4月于我院诊治的GDM孕妇为研究对象,所有患者均符合《妇产科学》中关于GDM的诊断标准,另选取68例正常孕妇为对照组。采用葡萄糖氧化酶法检测血糖水平(空腹血糖及餐后2 h血糖水平),采用免疫凝集法检测和比较两组血清糖化血红蛋白(HbA1c)水平,采用免疫透射比浊法检测血清C反应蛋白(CRP)水平,并分析HbA1c与CRP的相关性。结果:GDM组患者空腹血糖(fasting plasma glucose,FPG)、2 h血糖(plasma glucose,PG)、血清HbA1c和CRP水平均显著高于正常组(P0.05),GDM患者血清Hb A1c和CRP水平呈显著正相关关系(r=0.654,P0.05)。结论:GDM患者血清HbAlC和CRP水平相较于正常孕妇有显著提高,且二者呈显著的正相关关系,二者联合检测可能作为GDM早期诊断的筛查的重要参考指标。     

Correlation between Serum Electrolytes and Fasting Glucose and Hb1Ac in Saudi Diabetic Patients

In subjects with impaired insulin action, alterations of the serum sodium and potassium concentrations have been reported. The resulting cationic imbalance, along with the osmotic effect of the elevated sugar levels, could influence the course of diabetes mellitus management. Therefore, this study was conducted to compare the fasting blood glucose and HbA1c levels with those of the serum electrolytes. Blood samples were collected for assessment of HbA1c, fasting blood glucose (FBS), and electrolytes using different automated methods. A significant association between the serum sodium and FBS levels among types 1 and 2 insulin-treated patients, and type 2 oral agent patients was observed. A total of 138 diabetic subjects were randomly selected from any gender aged between 25 and 65?years at the University Diabetes Center, King Saud University, Riyadh KSA. The subjects were classified into types 1 or 2 DM using ADA criteria. Blood samples were collected for assessment of HbA1c, FBS, and electrolytes using different automated methods. It showed a significant association between serum sodium, FBS among type 1, type 2 insulin treated, and type 2 oral agent groups. However, the association of sodium and HbA1c was insignificant when analyzed individually. A statistically significant association (P?相似文献   

Pioneer study: PPARgamma activation results in overall improvement of clinical and metabolic markers associated with insulin resistance independent of long-term glucose control.

New scores and biochemical markers have recently been published for diagnosis of insulin resistance and beta-cell dysfunction (such as intact proinsulin, adiponectin, IRISII-score). One goal of this 6-month prospective controlled study was to evaluate the impact of pioglitazone (45 mg) vs. glimepiride (1-6 mg, in the intend to optimize therapy) on these markers. Observation parameters were: IRIS-II score, HOMA-score, ATP III score, HbA (1c), fasting glucose, lipids, intact proinsulin, adiponectin, and adverse events. The study was completed by 173 patients (66 female, 107 male, age +/- STD: 63 +/- 8 years, disease duration: 7.2 +/- 7.2 years, HbA (1c): 7.53 +/- 0.85 %, pioglitazone arm: 89 patients). The groups were not different for any of the observation parameters at baseline, and a similar reduction in HbA (1c) was seen in both groups (p < 0.001). In the pioglitazone group, reductions were observed for the IRIS-II and HOMA scores (p < 0.001 vs. glimepiride at endpoint) fasting glucose (p < 0.001), insulin (p < 0.001), LDL/HDL ratio (p < 0.001), hsCRP (p < 0.05), intact proinsulin (p < 0.001), and an increase was seen in HDL (p < 0.001), adiponectin (p < 0.001) and BMI (p < 0.001). In conclusion, treatment with pioglitazone resulted in an improvement of markers for insulin resistance and beta-cell dysfunction, independent from blood glucose control. Adiponectin, intact proinsulin, and the IRIS-II score may be suitable parameters for monitoring of these additional beneficial therapeutic effects.     

Effect of a two-month detraining on glucose tolerance and insulin sensitivity in athletes--link to adrenal steroid hormones

Reduction in physical activity has been demonstrated to associate with the increased risk in insulin resistance and type 2 diabetes. To determine whether alteration in insulinemia, due to abstention from regular exercise training, is associated with changes in serum dehydroepiandrosterone sulfate (DHEA-S) and cortisol, 18 highly trained badminton players (21.2 +/- 0.3 years) were enrolled into a 2-month detraining study. Fasting serum insulin, glucose, DHEA-S, and cortisol were determined at trained state and at day 60 of detraining. Glucose tolerance and insulin sensitivity were assessed by an oral glucose tolerance test (OGTT). The 2-month detraining increased fasting glucose and insulin concentrations and body weight slightly, but did not significantly affect glucose tolerance and insulin response curve, in which 10 subjects had increased and 8 subjects had slightly decreased in the area under curve for insulin (IAUC). In the subjects with increased IAUC, serum cortisol was also elevated (from 0.44 +/- 0.07 to 0.83 +/- 0.26 U/l, P < 0.05) in parallel, and serum creatine kinase (CK) was unaltered during detraining. Whereas in the subjects with decreased IAUC, serum cortisol (from 0.51 +/- 0.19 to 0.54 +/- 0.14 U/l, no significance) was not changed and serum creatine kinase (from 461 +/- 179 to 151 +/- 21 U/l) was decreased during detraining. Two groups of detrained subjects exhibited a similar reduction in serum DHEA-S levels and slight elevation in body weight. The novel finding of the study is that the changes in serum cortisol, but not DHEA-S, were associated with the change in insulin sensitivity during early phase of lifestyle change from physically active to sedentary, and this response appears to be varied individually among athletes.     

Increased insulin-insensitive glucose transport in polymorphonuclear leukocytes from non-insulin-dependent diabetic patients.

We studied the transport rate of a non-metabolizable hexose analogue, 3-O-methyl-D-glucose, in polymorphonuclear leukocytes (insulin-insensitive cells) from patients with untreated non-insulin-dependent diabetes mellitus. The mean glucose transport rate was significantly elevated in the diabetic patients compared with healthy controls (13.3 +/- 3.7 vs 10.4 +/- 2.5 fl/cell.sec, mean +/- SD, p less than 0.01). In the diabetic subjects, glucose transport rates were positively correlated with HbA1c levels (r = 0.563, p less than 0.01) but had no relations with ambient plasma glucose concentrations. Short-term incubation with 20 mM D-glucose had no effect on glucose transport in those cells. When glucose transport rates, HbA1c and fasting plasma glucose levels were simultaneously measured at weekly intervals over a four-week period in three diabetic subjects, the alterations in transport rates generally paralleled the changes observed in HbA1c levels rather than plasma glucose concentrations. It can be concluded that unlike insulin-sensitive cells such as adipocytes and muscle, glucose transport in human polymorphonuclear leukocytes, which are insulin insensitive cells, is increased in patients with non-insulin-dependent diabetes mellitus. Long-term, not short-term, derangement of glucose metabolism seems to be associated with increased glucose transport rate found in those patients.     

Dehydroepiandrosterone decreases elevated hepatic glucose production in C57BL/KsJ-db/db mice

Dehydroepiandrosterone (DHEA) is known to improve hyperglycemia in diabetic db/db mice that are obese and insulin resistant. In a previous study, we reported that DHEA suppresses the elevated hepatic gluconeogenic glucose-6-phosphatase (G6Pase) activity and gene expression in C57BL/KsJ-db/db mice. In the present study, we evaluated the total amount of gluconeogenesis using NaH[(14)C]CO(3) and hepatic glucose production using fructose as a substrate in primary cultured hepatocytes. Despite hyperinsulinemia, the glucose production of db/db mice in the total body and hepatocytes was elevated as compared to their heterozygote littermate C57BL/KsJ-db/+m mice. Administration of DHEA significantly decreased the blood glucose level and increased the plasma insulin level in db/db mice. Administration of DHEA decreased the elevated total body and hepatic glucose production in db/db mice. In addition, the glucose production in the primary cultured hepatocytes of db/db mice was decreased significantly by the direct addition of DHEA or DHEA-S to the medium. These results suggest that administration of DHEA suppresses the elevated total body and hepatic glucose production in db/db mice, and this effect on the liver is considered to result from increased plasma insulin and DHEA or DHEA-S itself.     

2 型糖尿病患者血浆成纤维细胞生长因子-21 水平的变化及意义

目的:探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者血浆成纤维细胞生长因子-21(fibroblast growth factor 21,FGF-21)水平变化以及观察短期胰岛素强化治疗对FGF-21水平的影响。方法:选择我院2013年1月至2015年1月收治的T2DM患者64例,其中初诊T2DM患者32例(T2DM组),T2DM合并大血管病变患者32例(合并大血管病变组),并选择同期体检健康者30例(对照组)。采用酶联免疫法测定三组血浆FGF-21水平以及胰岛素强化治疗前后的变化,分析血浆FGF-21水平与体质量指数(BMI)、腰臀比(WHR)、血脂、血糖、空腹血浆胰岛素(FINS)和糖化血红蛋白(Hb A1C)等水平的关系。结果:T2DM组及T2DM合并大血管病变组患者空腹血浆FGF-21水平明显高于对照组(P0.05),T2DM合并大血管病变组患者空腹血浆FGF-21水平明显高于T2DM组和对照组(P0.05)。空腹血浆FGF-21水平与T2DM患者FPG、Hb A1C水平呈明显正相关,WHR、舒张压、Hb A1C是影响血浆FGF-21水平的独立相关因素。经胰岛素强化治疗后,血浆FGF-21水平较治疗前明显下降(P0.05)。结论:T2DM患者血浆FGF-21水平明显升高,可能参与了T2DM及其大血管病变的发生和发展,胰岛素强化治疗可明显降低T2DM患者血浆FGF-21水平,血浆FGF-21可能作为T2DM病情和疗效评估的参考指标。     

Glucagon-Like Peptide-1 Secretory Function as an Independent Determinant of Blood Pressure: Analysis in the Tanno-Sobetsu Study

Aims

Roles of glucagon-like peptide-1 (GLP-1) in extra-pancreatic tissues remain unclear. The aim of this study was to examine determinants of GLP-1 secretory function and possible contribution of GLP-1 to blood pressure (BP) regulation.

Methods and Results

We recruited 128 subjects who received annual examinations and 75g-oral glucose tolerance tests (OGTT) in the Tanno-Sobetsu cohort. Subjects on regular medications for cardiovascular and/or metabolic diseases were excluded, and data for the remaining 103 subjects were used for the univariate and multivariate analyses. Age, plasma glucose (PG), hemoglobin A1c (HbA1c), plasma insulin, and serum lipids were not selected as independent determinants of fasting GLP-1 level by multiple linear regression analysis. However, age and female sex were selected as independent positive determinants of the area under the curve of GLP-1 level during OGTT (AUC_GLP-1), an index of GLP-1 secretory function. Multiple linear regression analysis indicated that AUC_GLP-1 was an independent negative predictor of systolic BP (SBP), while AUC_GLP-1 was not correlated with fasting PG or HbA1c level. In subgroup analyses using the median of AUC_GLP-1 to divide the study subjects into high and low GLP-1 response groups, AUC_GLP-1 was significantly correlated with both SBP and diastolic BP (r = 0.40 and 0.28, respectively) in the low GLP-1 response group but not in the high GLP-1 response group.

Conclusions

The results of the present study suggest that GLP-1 secretory function is involved in prevention of BP elevation and that the GLP-1 response to oral glucose rather increases with aging perhaps as an adaptive phenomenon.     

Hormonal changes during puberty. IV. Longitudinal study of acrenal androgen secretions.

Longitudinal studies of plasma dehydroepiandrosterone sulfate (DHEA-S) and dehydroepiandrosterone (DHEA) were made in 13 girls aged 7 years and 14 aged 10 years, during 3 years, at 6-month intervals. Similarly, two groups of 12 boys aged 8 years and 11 years were followed. In addition, 3 girls with premature adrenarche and 4 male patients with Addison's disease were studied. In the normal girls a significant rise of plasma DHEA-S and DHEA occurred from 6 years of bone age (51.4 +/- 9.0 ng/ml and 50.5 +/-9.2 ng/100 ml, respectively) to 8 years (119. 7 +/- 19.1 ng/ml and 94.5 +/- 16.5 ng/100 ml). A further significant rise was apparent at 11 years (385.8 +/-60.9 ng/ml) and 329.0 +/- 78.4 ng/100 ml). In boys, a similar rise of DHEA-S and DHEA was observed between 6 years of bone age (75.8 %/- 12 ng/ml and 44.3 +/- 7.6 ng/100 ml) and 8 years (157.4 +/- 28.9 ng/ml and 76.1 +/- 8.9 ng/100 ml). Furhter significant rise of DHEA-S and DHEA were seen at 13 years of bone age (563.7 +/- 123.7 ng/ml and 267.9 +/- 50.0 ng/100 ml, respectively). Testosterone in both sexes rose 2-3 years later than DHEA-S and DHEA. In female patients with premature adrenarche, higher plasma levels of DHEA-S and DHEA were found when compared to normal levels at similar chronological and bone ages. Very low plasma concentrations of DHEA-S and DHEA were obsrved in the patients with Addison's disease.     

Effect of resistance exercise on dehydroepiandrosterone sulfate concentrations during a 72-h recovery: relation to glucose tolerance and insulin response

Serum dehydroepiandrosterone sulfate (DHEA-S) concentration is known to be associated with the whole-body insulin sensitivity. The main purpose of the study was to investigate the effect of resistance exercise on DHEA-S concentration during a 72 h post-exercise recovery, and its relation to glucose tolerance and insulin sensitivity. Morning fasted serum samples was obtained from 19 male volunteers (aged 21.1+/-0.4 years) 24 h before the onset of exercise and 24 h, 48 h, and 72 h following exercise for measurements of DHEA-S, cortisol, and TNF-alpha. Oral glucose tolerance test (OGTT) and insulin response were determined 24 h before and 48 h after exercise. We found that resistance exercise causes a delayed suppression in serum DHEA-S levels during recovery (48 h and 72 h). This exercise challenge did not affect glucose tolerance, but insulin response during OGTT was significantly elevated. The increased insulin level was not associated with serum levels of cortisol and TNF-alpha. In conclusion, the present study found that resistance exercise has a DHEA-S lowering effect that persisted for 72 h. This change could be related to the elevated insulin concentrations during OGTT.     

Association of serum adiponectin concentration to lipid and glucose metabolism in healthy humans.

BACKGROUND: Adiponectin is a recently discovered plasma protein with many associations to glucose and lipid metabolism. Due to its central role in cardiovascular diseases and insulin resistance, we studied the relationship between serum adiponectin and factors reflecting glucose and lipid metabolism. METHODS AND RESULTS: Thirty healthy participants (20M/10F, age 32.0 +/- 2.1 years, BMI 25.8 +/- 0.9 kg/m (2) and HbA (1c) 5.2 +/- 0.1 %) were studied four times at approximately one week intervals. The effects of a 4-hour euglycemic hyperinsulinemia (40 mU/m (2)/min), saline infusion (control), oral glucose, and oral fat load on serum adiponectin were studied. No significant correlation was found between serum adiponectin and insulin sensitivity before (r = 0.25) or after adjustment for age, BMI and gender (r = 0.04). Adiponectin concentration correlated inversely with HbA (1c) (r = - 0.43, p < 0.05), insulin concentration (r = - 0.38, p < 0.05) and triglyceride concentration (r = - 0.42, p < 0.05) but positively with HDL cholesterol (r = 0.38, p < 0.05). Metabolic procedures had no effect on serum adiponectin. CONCLUSIONS: Our findings favor the interpretation that adiponectin is not causally related to insulin sensitivity in healthy participants. The strongest associations of adiponectin in healthy participants are to be found to lipid metabolism. Serum levels of adiponectin are very stable and not acutely affected by hyperinsulinemia, oral glucose or fat load.