Serum beta-glycosidases in diabetes mellitus

Levels of fasting blood glucose, serum beta-glucuronidase and beta-N-acetylglucosaminidase in 47 Libyan diabetic patients were determined. The respective mean values were 254.5 +/- 11 mg/dl, 74 +/- 5.7 Sigma units/ml and 171.8 +/- 25.5 microM PNP/dl. The mean body mass index and duration of diabetes of the patients were 30.5 +/- 0.91 kg/m2 and 7.5 +/- 1.16 years, respectively. Statistically significant correlations were found between fasting blood glucose and serum beta-glucuronidase levels (r = 0.65; p less than 0.001) and also between fasting blood glucose and beta-N-acetylglucosaminidase levels (r = 0.58; p less than 0.001). The activities of these two enzymes increase in serum with increasing fasting blood glucose levels. Patients with positive family history of diabetes have higher activities of these two enzymes than those without positive history of diabetes in the family. Patients with secondary complications have both enzymes elevated as compared with patients without secondary complications. Female patients have higher beta-N-acetylglucosaminidase activity and lower beta-glucuronidase activity than males. Age and duration of diabetes do not appear to have any effect on the activities of these enzymes.     

Influence of short-term fasting on the pituitary-testicular axis in normal men

To investigate whether short-term fasting affects serum testosterone (T) in normal subjects, 10 healthy men of normal weight were studied on two occasions: after an overnight fast (8 h), and after an additional 48 h of fasting. Blood glucose declined by 22 +/- 3% between the tests (p less than 0.001). Basal serum T fell from 8.7 +/- 0.7 to 5.7 +/- 0.8 micrograms/l (p less than 0.01), and LH from 6.9 +/- 0.8 to 5.0 +/- 0.7 U/l (p less than 0.01). Serum estradiol (E2) and FSH remained unaffected. To explore possible mechanisms behind the decreased basal release of T and LH, 9 small doses of glucose were given orally at regular intervals during a 56-hour fast to 9 additional normal men to maintain blood glucose levels. These men did not experience a fall in serum T or LH. Six additional normal men were given 50 micrograms GnRH intravenously after an overnight fast, and after a fasting period of 56 h. No acute increase in T was seen after the overnight fast, but after the 56-hour fast GnRH raised serum T by 55 +/- 14% (p less than 0.02). Moreover, fasting augmented the GnRH-induced LH response by 64 +/- 15% (p less than 0.02. These results imply that: short-term fasting exerts inhibitory influence on Leydig cell function via a mechanism which might involve a reduced hypothalamic and/or pituitary stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of obesity on erythrocyte count and hemoglobin levels in Libyan diabetic patients

Fasting blood glucose, erythrocyte count and hemoglobin levels of obese and nonobese Libyan diabetic women were determined. The mean values of fasting blood glucose, erythrocyte count and hemoglobin of obese diabetic women were 209.55 +/- 8.85 mg/dl, 4.986 +/- 0.04 X 10(6)/mm3 and 14.51 +/- 0.18 g/dl. The respective values for nonobese diabetic women were 243.47 +/- 12.56 mg/dl, 4.865 +/- 0.06 X 10(6)/mm3 and 14.31 +/- 0.19 g/dl. The mean values of the three variables of obese patients were significantly different from those of the nonobese patients. Statistically significant correlations were found between fasting blood glucose levels and erythrocyte count, and hemoglobin levels in both obese and nonobese patients. The levels of erythrocyte count and hemoglobin of obese patients were higher than those of their nonobese counterparts. This elevation was attributed to the effect of obesity. It is suggested that regulation of body weight should be considered an essential step in the management of diabetes.     

Indices of iron and copper status during experimentally induced,marginal zinc deficiency in humans

This study examined the effect of diet-induced, marginal zinc deficiency for 7 wks in 15 men (aged 25.3 +/- 3.3 yrs; mean +/- SD) on selected indices of iron and copper status. The regimen involved low-zinc diets based on egg albumin and soy protein with added phytate and calcium such that mean [phytate]/[Zn] and [phytate] X [Ca]/[Zn] molar ratios were 209 and 4116, respectively, for 1 wk, followed by 70 and 2000, respectively, for 6 wks. Subjects were then repleted with 30 mg Zn/d for 2 wks. Plasma copper, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) activity in plasma and red blood cells (RBC), hemoglobin, hematocrit, and serum ferritin were determined weekly on fasting blood samples. Significant reductions (p less than 0.05) after 7 wks in RBC Cu,Zn-superoxide dismutase (49.5 +/- 7.2 vs 33.6 +/- 6.3 U/mg Hb) and serum ferritin (69.2 +/- 38.7 vs 53.8 +/- 33.7 micrograms/L) occurred; no comparable decline was noted for plasma Cu, hemoglobin, or hematocrit. Significant (p less than 0.05) but less consistent changes were also observed in plasma superoxide dismutase activity. None of the changes were associated with the decreases in plasma, urinary and hair zinc concentrations, and alkaline phosphatase activity in RBC membranes. Results indicate that the biochemical iron and copper status of the subjects was marginally impaired, probably from the dietary regimen that induced marginal zinc deficiency.     

Efficacy and safety of Touchi extract, an alpha-glucosidase inhibitor derived from fermented soybeans, in non-insulin-dependent diabetic mellitus

The water-extracted Touchi, a traditional Chinese food, exerted a strong inhibitory activity against rat intestinal alpha-glucosidase in foodstuffs. In borderline and developed diabetic subjects, 0.3 g of Touchi-extract (TE) significantly inhibited postprandial blood glucose levels. For confirmation of safety, 9 healthy subjects were given 1 g of TE before every meal (3 g/day) for 12 weeks. None indicated changes in hematological and relevant biochemical parameters, body weight or BMI. In a non-comparative study, 18 type-2 diabetic patients ingested 0.3 g of TE before every meal (0.9 g/day) for 6 months (mo). Blood glucose (mean; 9.31 +/- 0.71 mmol/L) and HbA(1c) (mean: 10.24 +/- 0.58%) levels gradually decreased, and significant effects were elicited on the blood glucose levels (8.61 +/- 0.66 mmol/L; p < 0.01) after 6 mo and HbA(1c) after 3 (9.13 +/- 0.43%; p < 0.05) and 6 mo (8.96 +/- 0.30%; p < 0.05) post-ingestion of TE. Indexes for serum lipids and total cholesterol level revealed moderate decreases with a slight increase in the high-density lipoprotein (HDL) level after TE ingestion. However, triglyceride (TG) levels significantly decreased at 3 (p < 0.05) and 6 mo (p < 0.01) post-ingestion of TE. In this study, other biochemical parameters were not affected in any of the patients, and no one complained of any side-effects or abdominal distension. TE, exhibiting alpha-glucosidase inhibitory activity, demonstrated an anti-hyperglycemic effect and may prove useful for improving glycemic control in patients suffering from non-insulin-dependent diabetic mellitus.     

Gamma-glutamyltranspeptidase and alkaline phosphatase serum activities: their relation to the outcome of Graves' disease

Gamma-glutamyltranspeptidase (GGT) and alkaline phosphatase (ALP) were assayed in the sera of 27 patients affected with Graves' disease prior to conventional (12-18 months) methimazole (30-5 mg/day) treatment, who were subsequently followed up over 36 +/- 1.5 months (m +/- SEM). Twelve patients underwent recurrence of thyrotoxicosis (relapsers) at variable intervals from withdrawal of treatment, whereas the remaining 12 remained euthyroid (nonrelapsers). In the study group as a whole, both GGT and ALP serum levels were significantly (p less than 0.001) increased with respect to 24 sex- and age-matched euthyroid controls (31.8 +/- 3.6 vs. 11.5 +/- 1.2 U/l and 203 +/- 13.8 vs. 110 +/- 7.3 U/l, m +/- SEM). Prevalence of GGT and ALP elevations was 56% (15/27) and 58% (15/26), respectively. Serum GGT activity was age dependent (r = 0.466, p less than 0.05) and inversely related to log2 microsomal antibody initial titer (r = 0.499, p less than 0.05) in the whole series. There was no difference in mean pretreatment thyroxine (T4) or triiodothyronine (T3) between the groups with supranormal enzyme and normal enzyme levels. However, in the group with enhanced enzyme levels, relapsed patients had higher initial T4 (20.3 +/- 0.8 vs. 17.1 +/- 0.7 micrograms/dl, p less than 0.01) and lower both initial T3 (452 +/- 31.1 vs. 551 +/- 57.8 ng/dl, p less than 0.02) than the nonrelapsed patients. Only in this group, initial T3:T4 ratio was a valuable indicator of the outcome of the disease, since it was below 30 in 7/7 (100%) relapsers vs. 2/8 (25%) nonrelapsers, but above 30 only in 6 subjects who remitted.     

Changes in maternal serum aldosterone, potassium and prolactin levels during beta-receptor agonist treatment in third trimester pregnancies

Beta-receptor agonist (terbutalin or isoxsuprin) administration to pregnant women either because of premature labor (therapy group; T; n = 8) or as prophylactic treatment (prophylaxis group; p; n = 8) resulted in a marked drop in serum potassium (p less than 0.001) during the first two hours of infusion in all patients. In five diabetic women in the P group the prolactin was significantly decreased (P less than 0.01) as was serum aldosterone levels (p less than 0.01). These changes were not observed in the T group. The two groups of pregnant women responded with a significant increase in free fatty acids (FFA) and glucose but the magnitude and the time coarse differed. Thus in T women, FFA reached a peak after 30-60 minutes into treatment and then returned to baseline levels. A closer analysis revealed that this pattern was only obtained in patients receiving terbutalin. Among women given prophylactic treatment with terbutalin, a continuous increase in FFA was noted over the initial two hours (p less than 0.001). The increase in serum glucose was continuous in the two patient groups (p less than 0.001). It is suggested that beta-receptor agonists in diabetic women induces a dopaminergic type of response since serum prolactin levels but not TSH concentrations were affected. The possibility that an increased PGE2 synthesis at the expense of PGF2 alpha might mediate this effect of beta-receptor agonists in discussed. It is also suggested that an increased prostaglandin synthesis might interfere with aldosterone secretion. The possibility that falling serum potassium levels may activate dopaminergic systems via PGE2 synthesis is also emphasized.     

The antidiabetic activity of aloes: preliminary clinical and experimental observations

The dried sap of the aloe plant (aloes) is one of several traditional remedies used for diabetes in the Arabian peninsula. Its ability to lower the blood glucose was studied in 5 patients with non-insulin-dependent diabetes and in Swiss albino mice made diabetic using alloxan. During the ingestion of aloes, half a teaspoonful daily for 4-14 weeks, the fasting serum glucose level fell in every patient from a mean of 273 +/- 25 (SE) to 151 +/- 23 mg/dl (p less than 0.05) with no change in body weight. In normal mice, both glibenclamide (10 mg/kg twice daily) and aloes (500 mg/kg twice daily) induced hypoglycaemia after 5 days, 71 +/- 6.2 and 91 +/- 7.6 mg/dl, respectively, versus 130 +/- 7 mg/dl in control animals (p less than 0.01); only glibenclamide was effective after 3 days. In the diabetic mice, fasting plasma glucose was significantly reduced by glibenclamide and aloes after 3 days. Thereafter only aloes was effective and by day 7 the plasma glucose was 394 +/- 22.0 versus 646 +/- 35.9 mg/dl, in the controls and 726 +/- 30.9 mg/dl in the glibenclamide treated group (p less than 0.01). We conclude that aloes contains a hypoglycaemic agent which lowers the blood glucose by as yet unknown mechanisms.     

Plasma tumor necrosis factor-alpha levels and insulin resistance in nondiabetic hypertensive subjects

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is associated with insulin resistance in certain conditions. However, whether TNF-alpha is related to insulin resistance in hypertensive subjects is still controversial. The aim of this study was to determine the status of TNF-alpha and insulin resistance in hypertension. METHODS: Newly diagnosed nondiabetic 17 essentially hypertensive (6 men, 11 women) patients, and 11 control healthy subjects (5 men, 6 women) are involved in the study. Body mass index (BMI), insulin, fasting blood glucose, cholesterol, triglyceride, and TNF-alpha levels were measured. Insulin resistance is assessed according to homeostasis model of assessment (HOMA-IR). RESULTS: Serum insulin (8.4 +/- 2.7 vs. 6.1 +/- 1.4 mIU/ml; p < 0.01), triglyceride (245.0 +/- 39.9 vs. 193.0 +/- 22.8 mg/dl; p < 0.01), and TNF-alpha (4.2 +/- 0.7 vs. 3.0 +/- 0.6 pg/ml; p < 0.001) levels, and HOMA-IR (2.0 +/- 0.8 vs. 1.3 +/- 0.3; p < 0.001) were significantly higher in the hypertensive patients compared to the normotensive control group. There were positive correlations between TNF-alpha levels and body mass index (r = 0.64, p < 0.01), and triglyceride (r = 0.55 p = 0.02) levels in the whole study group. However, there was no correlation of either TNF-alpha or HOMA-IR. CONCLUSIONS: Our data revealed that hypertensive patients have insulin resistance and higher TNF-alpha levels, but there is no relation between TNF-alpha levels and insulin resistance.     

Influence of thyroid function on serum bone Gla protein

The serum BGP level was assayed in patients with hyperthyroidism (untreated and remittent cases) and hypothyroidism. The mean serum BGP concentration was 9.7 +/- 0.90 ng/ml in 30 patients with untreated hyperthyroidism which was significantly higher than the 2.7 +/- 0.38 ng/ml in 15 remittent patients and 1.3 +/- 0.31 ng/ml in 13 patients with hypothyroidism (p less than 0.001, p less than 0.001). Serum BGP had a significant positive correlation with the concentrations of free triiodothyronine and alkaline phosphatase in the serum, while it had a significant negative correlation with serum PTH. In the patients with hypothyroidism, serum BGP increased significantly in parallel with increases in serum free triiodothyronine with thyroxine therapy. In the patients with hyperthyroidism, serum free triiodothyronine decreased significantly after the first month of methimazole treatment, and fluctuated within the normal range after two months. Serum alkaline phosphatase and BGP did not show significant changes during the first six months of treatment, although they were eventually reduced significantly at the end of one year. These results suggest that thyroid hormone directly stimulates the synthesis and secretion of BGP in existent osteoblasts and also acts on the bone remodeling cycle, therapy accelerating the rate of bone formation; the latter action may occur over a long period.     

The effect of calcium supplements on plasma alkaline phosphatase and urinary hydroxyproline in postmenopausal women

Although calcium supplements are widely used in the treatment of osteoporosis, their beneficial effect is not conclusively established. We now report some effects of a calcium supplement (1 g/day) given for 6 to 12 weeks to 15 postmenopausal osteoporotic women. The mean fasting urinary hydroxyproline/creatinine ratio decreased from 0.021 +/- 0.002 to 0.015 +/- 0.001 (P less than 0.0025), indicating a significant reduction in bone resorption. The mean plasma alkaline phosphatase fell from 123 +/- 5 U/l to 104 +/- 3.1 U/l (P less than 0.01), probably representing some secondary reduction in bone formation following the inhibition of bone resorption. These results support the concept that calcium supplementation is useful in the treatment of postmenopausal osteoporosis.     

Serum levels of TNF-alpha,sIL-2R,IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet's disease

AIM: Behçet''s disease (BD) is asystemic immunoinflammatory disorder and the aetiopathogenesis is to be specified. Cytokines play a role in immune response and in many inflammatory diseases. The aim of this case-control study is to investigate serum pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta), soluble IL-2 receptor (sIL-2R), IL-6, and chemokine IL-8 levels in patients with BD. We also determined the end product of lipid peroxidation (malondialdehyde (MDA)) in BD patients as an index for oxidative stress. METHODS: A total of 37 patients (19 men, 18 women) with BD (active, n = 17; inactive, n = 20) and 20 age-matched and sex-matched healthy control subjects (11 men, nine women) included in this cross-sectional, blinded study. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a spectrophotometer technique using the immulite chemiluminescent immunometric assay. Lipid peroxidation was evaluated by Wasowicz et aL The levels of cytokines and lipid peroxidation in the active period were compared with the inactive period of the disease. Results are expressed as mean +/- standard error. RESULTS: IL-1beta levels were below the detection limits of the assay (< 5 pg/ml) in all samples. Mean levels of MDA (8.1+/-0.7 micromol/l), sIL-2R (800+/-38 U/ml), IL-6 (12.6+/-1.1 pg/ml), IL-8 (7.2+/-0.4 pg/ml), and TNF-alpha (7.9+/-0.5 pg/ml) in active BD patients were significantly higher than those in inactive patients (4.3+/-0.5 micromol/l, p < 0.01; 447+/-16 U/ml, p < 0.001; 8.3+/-0.6 pg/ml, p = 0.006; 5.3+/-0.1 pg/ml, p < 0.001; and 5.1 0.2 pg/ml, p < 0.001; respectively) or control subjects (2.1+/-0.2 micromol/l, p < 0.001; 446+/-20 U/ml, p < 0.001; 6.4+/-0.2 pg/ml, p < 0.001; 5.4+/-0.1 pg/ml, p < 0.001; and 4.7+/-0.1 pg/ml, p < 0.001, respectively). On the contrary, only the mean IL-6 level was significantly different between inactive BD and control subjects (p = 0.02). All acute phase reactants were significantly higher in active BD than in inactive period (for each, p < 0.01). Conclusions: High levels of sIL-2R, IL-6, IL-8 and TNF-alpha indicate the activation of immune system in BD. Serum sIL-2R, IL-6, IL-8 and TNF-alpha seem to be related to disease activity. Increased lipid peroxidation suggests oxidative stress in BD and therefore tissue damage in such patients. Amelioration of clinical manifestations would be envisaged by targeting these cytokines, chemokines and lipid peroxidation with pharmacological agents.     

The effect of exogenous growth hormone on insulin requirements during closed loop insulin delivery in insulin-dependent diabetes mellitus

The amount of insulin required to maintain similar blood glucose concentrations during an eight hour infusion of either saline or growth hormone (2 micrograms/kg/hr) was determined in five fed, insulin-dependent diabetic subjects during closed-loop insulin delivery. Elevations of serum growth hormone concentrations to levels previously observed in poorly controlled diabetic subjects were not accompanied by differences in the amount of insulin required to maintain blood glucose concentrations at levels comparable to those observed during the saline infusion. Specifically, no early insulin-like nor late anti-insulin effects of physiologic increases in serum growth hormone concentrations (10.27 +/- 0.23 mg/ml vs 5.69 +/- 1.5 mg/ml, P less than 0.05) on mean hourly blood glucose levels or mean hourly insulin requirements were observed. These studies suggest that serum growth hormone concentrations similar to those observed in poorly controlled diabetics do not affect the insulin requirements of well-insulinized diabetic subjects.     

Reversibility of decreased insulin-stimulated glucose transport capacity in diabetic muscle with in vitro incubation. Insulin is not required

The mechanisms by which insulin deficiency affects muscle glucose transport were investigated. Epitrochlearis muscles from rats with streptozotocin-induced diabetes and from controls were incubated in vitro for 0.5-14 h. The incubation was shown not to impair muscle energy stores or tissue oxygenation. Diabetes decreased basal 3-O-methylglucose transport by 40% (p less than 0.01), and insulin-stimulated (20 milli-units/ml) glucose transport capacity by 70% (p less than 0.001). In vitro incubation gradually normalized insulin responsiveness (3.77 +/- 0.38 before versus 8.97 +/- 0.65 mumol X ml-1 X h-1 after 12 h of incubation). Basal glucose transport remained significantly reduced. The reversal of the insulin responsiveness did not require the presence of rat serum and, furthermore, took place even in the absence of insulin. In fact, insulin responsiveness was higher after incubation (14 h) with no insulin than with 100 microunits/ml insulin (9.85 +/- 0.59 versus 8.06 +/- 0.59 mumol X ml-1 X h-1, p less than 0.05). Glucose at 30 mM did not affect the normalization of the insulin-stimulated glucose transport capacity, whereas incubation in serum from diabetic rats resulted in a slightly (26%) blunted reversal (7.60 +/- 0.39 versus 8.89 +/- 0.45 mumol X ml-1 X h-1 with diabetic versus control serum for 14 h, p less than 0.05; before incubation the value was 3.87 +/- 0.40). Inhibition of protein synthesis by cycloheximide blocked the normalization by 80%. These results suggest the presence in diabetic serum of some labile factor that might inhibit the glucose transport system. The results indicate that the decreased insulin-stimulated glucose transport capacity, in the insulin-deficient diabetic muscle, is not a direct consequence of the lack of insulin or of high glucose concentrations.     

Levels of Catechols in Epileptogenic and Nonepileptogenic Regions of the Human Brain

Recent reports about tyrosine hydroxylase and alpha 1-adrenoceptors in epileptic foci have suggested increased regional catecholaminergic activity, which may serve a compensatory, inhibitory role. We measured levels of catechols, including the precursor 3,4-dihydroxyphenylalanine (DOPA) and the catecholamines dopamine (DA) and norepinephrine (NE), in surgically removed foci identified by electrocorticography and in nonepileptogenic sites from 23 patients with intractable temporal lobe epilepsy. The following values (mean +/- 1 SD) were obtained: DOPA = 142 +/- 60 ng/g of protein in the focus vs. 115 +/- 39 ng/g in the nonfocus (p less than 0.01); DA = 168 +/- 85 vs. 106 +/- 54 ng/g (p less than 0.001); and NE = 267 +/- 117 vs. 181 +/- 80 ng/g (p less than 0.001). The results are consistent with increased catecholaminergic activity in epileptic foci.     

Diabetes-induced decrease in rat brain microsomal Ca2+-ATPase activity

The Ca(2+)-ATPase activity of rat brain microsomes was studied in streptozotocin (STZ)-induced diabetes. Male rats, 200-250 g, were rendered diabetic by injection of STZ (45 mg kg(-1) body weight) via the teil vein. Brain tissues were collected at 1, 4 and 10 weeks after diabetes was induced for determination of Ca(2+)-ATPase activity, lipid peroxidation and tissue calcium levels. Diabetic rats had significantly elevated blood glucose levels compared to controls. Blood glucose levels were 92.92 +/- 1.22 mg dl(-1) (mean +/- SEM) for the control group, 362.50 +/- 9.61 mg dl(-1) at 1 week and >500 mg dl(-1) at 4, 8 and 10 weeks for the diabetics. Enzyme activities were significantly decreased at 1, 4, 8 and 10 weeks of diabetes relative to the control group (p < 0.001). Ca(2+)-ATPase activity was 0.084 +/- 0.008 U l(-1), 0.029 +/- 0.005 U l(-1), 0.029 +/- 0.006 U l(-1), 0.033 +/- 0.003 U l(-1) and 0.058 +/- 0.006 U l(-1) (mean +/- SEM) at control, 1, 4, 8 and 10 week of diabetes respectively. The change in calcium levels in diabetic rat brain at 8 and 10 weeks of diabetes was significantly higher than that of the control group (p < 0.05). On the other hand lipid peroxidation measured as TBARS (thiobarbituric acid reactive substances) was significantly higher at 8 and 10 weeks of diabetes (p < 0.05). The increase in lipid peroxidation observed in diabetic rat brain may be partly responsible for the decrease in calcium ATPase activity.     

Effect of parathyroid function on serum bone Gla protein

The serum bone Gla protein (BGP) level was measured in patients with idiopathic hypoparathyroidism, and primary hyperparathyroidism, and normal volunteers. The mean serum BGP level was 4.5 +/- 0.20 micrograms/l in 40 normal volunteers. It was significantly lower in 12 patients with idiopathic hypoparathyroidism (1.6 +/- 0.21 micrograms/l, p less than 0.001) and significantly higher in 33 patients with primary hyperparathyroidism (13.0 +/- 1.3 micrograms/l, p less than 0.001). When a single intravenous injection of 30 micrograms of human PTH 1-34 was administered to the patients with idiopathic hypoparathyroidism, there was no significant change in serum BGP within the next 24 hours. Following a therapeutic oral dose of alfacalcidol, serum BGP was appreciably increased (p less than 0.001) from the preadministration value of 1.6 +/- 0.21 micrograms/l to 3.9 +/- 0.34 micrograms/l. In patients with primary hyperparathyroidism, the surgical excision of parathyroid adenoma led to a sharp decrease in serum PTH but a gradual decrease in serum BGP. The latter approximately paralleled the decline in serum alkaline phosphatase. Thus, serum BGP is a marker that reflects bone turnover status in parathyroid disease. It appears that the active form of vitamin D directly increases the secretion of BGP in existing osteoblasts and PTH mainly affects serum BGP to stimulate the bone remodeling cycles with its long term effect.     

Glucose kinetics differ between women and men, during and after exercise.

As exercise can improve the regulation of glucose and carbohydrate metabolism, it is important to establish biological factors, such as sex, that may influence these outcomes. Glucose kinetics, therefore, were compared between women and men at rest, during exercise, and postexercise. It was hypothesized that glucose flux would be significantly lower in women than men during both the exercise and postexercise periods. Subjects included normal weight, healthy, eumenorrehic women and men, matched for habitual activity level and maximal oxygen uptake per kilogram lean body mass. Testing occurred following 3 days of diet control, with no exercise the day before. Subjects were tested in the overnight-fasted condition with women studied in the midluteal phase of the menstrual cycle. Resting (120 min), exercise (85% lactate threshold, 90 min), and postexercise (180 min) measurements of glucose flux and substrate metabolism were made. During exercise, women had a significantly lower rate of glucose appearance (Ra) (P<0.001) and disappearance (Rd) (P<0.002) compared with men. Maximal values were achieved at 90 min of exercise for both glucose Ra (mean+/-SE: 22.8+/-1.12 micromol.kg body wt-1.min-1 women and 33.6+/-1.79 micromol.kg body wt-1.min-1 men) and glucose Rd (23.2+/-1.26 and 34.1+/-1.71 micromol.kg body wt-1.min-1, respectively). Exercise epinephrine concentration was significantly lower in women compared with men (P<0.02), as was the increment in glucagon from rest to exercise (P<0.04). During the postexercise period, glucose Ra and Rd were also significantly lower in women vs. men (P<0.001), with differences diminishing over time. In conclusion, circulating blood glucose flux was significantly lower during 90 min of moderate exercise, and immediately postexercise, in women compared with men. Sex differences in the glucagon increase to exercise, and/or the epinephrine levels during exercise, may play a role in determining these sex differences in exercise glucose turnover.     

Diagnostic value of serum IGF-I and IGFBP-3 in growth hormone disorders in adults

OBJECTIVE: To investigate the diagnostic value of serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) measurements in adult patients with acromegaly and GH deficiency (GHD). METHODS: Serum IGF-I and IGFBP-3 levels were measured in 39 active acromegalic patients, 34 adult patients with GHD and 150 healthy adults. Disease activity in patients with acromegaly was confirmed by nadir GH levels during an oral glucose tolerance test (OGTT). Among patients with acromegaly, 15 had not been treated previously and 24 had been treated but not cured. GHD in adults was diagnosed by an insulin tolerance test (ITT). Among patients with GHD, 15 were aged 20-40 years (9 men and 6 women) and 19 were aged over 40 years (9 men and 10 women). One hundred and fifty healthy subjects were recruited as a control group. To compare the individual serum IGF-I and IGFBP-3 levels of patients with the results of the gold standard, we calculated age- and sex-corrected standard deviation scores (SDS) for individual IGF-I and IGFBP-3 levels. The sensitivities of serum IGF-I and IGFBP-3 measurements for the disease diagnosis were analyzed using the mean +/- 2 SD of the values of healthy control subjects as a diagnostic cutoff, defining 95% specificity. RESULTS: The mean IGF-I and IGFBP-3 SDS levels were significantly higher in active acromegalic patients, both untreated and treated but not cured, than in the control subjects (p < 0.05). The sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of acromegaly were 97.4 and 81.8%, respectively. In untreated patients with acromegaly, the sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of disease were 100 and 100%, while these were 95.8 and 72.7% in treated patients with acromegaly. In adult patients with GHD, the mean IGF-I and IGFBP-3 SDS were significantly lower than those of the control subjects (IGF-I, -2.2 +/- 0.8 vs. 0.0 +/- 1.0 SDS, p < 0.0001); IGFBP-3, -1.7 +/- 1.2 vs. 0.0 +/- 1.0 SDS, p < 0.0001), but there was a considerable overlap between GHD in adults and the controls. In all patients with GHD, the sensitivities of serum IGF-I and IGFBP-3 measurements were 64.7 and 52.9%, respectively. In the group of women aged 20-40 years, the sensitivity of IGF-I measurement for the diagnosis of GHD was 100%, although the number of patients was only 6. CONCLUSION: Both serum IGF-I and IGFBP-3 measurements are comparable to an oral glucose tolerance test in patients with untreated acromegaly, but in acromegalic patients that have undergone surgery and/or radiotherapy, serum IGF-I is more valuable for determining disease activity than serum IGFBP-3. Serum IGF-I and IGFBP-3 measurements are not valuable for the diagnosis of GHD in adults, but in women aged 20-40 years serum IGF-I measurement appears to be useful in the diagnosis of GHD.     

Reduced ecto-5'-nucleotidase activity and enhanced OKT10 and HLA-DR expression on CD8 (T suppressor/cytotoxic) lymphocytes in the acquired immune deficiency syndrome: evidence of CD8 cell immaturity

Markedly reduced ecto-5'-nucleotidase activity was found in peripheral blood lymphocytes from 27 out of 30 homosexual men with the acquired immune deficiency syndrome (AIDS) in association with Kaposi's sarcoma (AIDS-KS; 2.67 +/- 1.70 U/10(6) cells; n = 13), opportunistic infections (AIDS-OI; 9.29 +/- 7.32; n = 7), or the AIDS-related complex (ARC; 9.82 +/- 6.12; n = 10). These values were significantly different from healthy controls (22.70 +/- 4.58; p less than 0.001). In AIDS-KS patients, both T cells and non-T cells exhibited significantly reduced ecto-5'-NT activity (p less than 0.001). AIDS-KS CD8 cells contained 20% of the mean ecto-5'-NT activity (7.04 +/- 3.53) displayed by control CD8 cells (34.07 +/- 4.86; p less than 0.001). No significant difference in enzyme level was observed between control and AIDS-KS CD4 cells (11.93 +/- 4.98 vs 7.98 +/- 3.28, respectively). In AIDS patients, lymphocyte ecto-5'-NT activity was inversely related (r = -0.518; p less than 0.01) to the absolute number of OKT10+ cells, but no correlation was found with the number of HLA-DR+ cells (r =-0.224). Two-color analysis of lymphocytes from AIDS-KS patients revealed that 75 +/- 12% of circulating CD8 cells expressed the OKT10 antigen, whereas only 10 +/- 6% of control CD8 cells did. HLA-DR antigens, which are not normally found on circulating resting T cells, were expressed in AIDS-KS CD8 cells, although to a lesser extent than OKT10. These data demonstrate that most AIDS CD8 cells differ from control CD8 cells. Although it has been suggested that these cells are activated cytotoxic or suppressor cells, the data presented here support the hypothesis they are immature. Reduced T cell ecto-5'-NT activity and enhanced expression of OKT10 and HLA-DR antigens on circulating CD8 cells, in conjunction with lack of transferrin receptor-(OKT9) and IL 2 receptor-(Tac) bearing lymphocytes, sustain this latter hypothesis. The correlation of the numerical reduction of CD4 cells with the reduced levels of ecto-5'-NT (r = 0.606; p less than 0.01) suggests that the abnormal maturation of CD8 cells seen in AIDS might be a consequence of the CD4 deficiency characteristic of this syndrome.