High prevalence of polycystic ovaries and associated clinical, endocrine, and metabolic features in women with previous gestational diabetes mellitus

The prevalence of polycystic ovaries, according to ultrasonography, and associated clinical, endocrine, and metabolic features were investigated in women with previous gestational diabetes mellitus (GDM). Thirty-four women with GDM 3-5 yr before the investigation and 36 controls with uncomplicated pregnancies, selected for similar age, parity, and date of delivery, were investigated. The women with previous GDM showed a higher prevalence of polycystic ovaries [14 of 34 (41%) vs. 1 of 36 (3%); P < 0.0001], hirsutism (P < 0.01), irregular menstrual cycles (P < 0.01), and a higher body mass index (BMI; P < 0.001) than the controls. Five women (15%) with previous GDM had developed manifest diabetes (excluded in comparisons of metabolic variables). After dividing the women with previous GDM into subgroups according to ovarian appearance, the 2 subgroups showed similar glucose tolerance and prevalence of diabetes, whereas the women with polycystic ovaries were younger (mean +/- SD, 33.3 +/- 1.4 vs. 38.2 +/- 1.1; P < 0.01), had higher truncal-abdominal/femoral fat ratio according to skin folds (P < 0.05), had higher concentrations of androstenedione (P < 0.01) and testosterone (P < 0.01), and had a higher LH/FSH ratio (P < 0.01), lower levels of GH (P < 0.01), higher levels of triglycerides (P < 0.05) and cholesterol (P < 0.05) in very low density lipoprotein, all independent of age and BMI, and had a higher prevalence of pregnancy-induced hypertension (50% vs. 15%; P < 0.05) during the index pregnancy compared with the women with normal ovaries. The group of women with GDM showed a lower early insulin release after glucose (i.v. glucose tolerance test) for their degree of insulin resistance (euglycemic hyperinsulinemic clamp) compared with controls (P < 0.05). In the two subgroups, insulin sensitivity was lower in the polycystic ovaries group, independent of BMI (P < 0.05), than in the group with normal ovaries. In conclusion, ultrasonographic, clinical and endocrine signs of polycystic ovary syndrome were much increased in women with a history of GDM. Compared with the women with normal ovaries and previous GDM, those with polycystic ovaries formed a distinct subgroup that may be more prone to develop various features of the insulin resistance syndrome. Both groups showed a similarly disturbed balance between beta-cell activity and insulin sensitivity, but in women with polycystic ovaries, insulin resistance may be the dominant component.     

Cesarean delivery in relation to birth weight and gestational glucose tolerance: pathophysiology or practice style? Toronto Trihospital Gestational Diabetes Investigators

OBJECTIVES: To examine the relationship between birth weight and mode of delivery among women with untreated borderline gestational diabetes mellitus (GDM), treated overt GDM, and normoglycemia. DESIGN: Prospective cohort study. SETTING: Three Toronto, Ontario teaching hospitals. PATIENTS: A total of 3778 volunteers aged 24 years or older. INTERVENTIONS: Subjects underwent a 3-hour long, 100-g oral glucose tolerance test at 28 weeks' gestation, regardless of screening test results. Usual care was provided to 143 women who met the National Diabetes Data Group criteria for GDM. Physicians were blinded to glucose tolerance test results for all others, including 115 untreated women with borderline GDM by the broader criteria of Carpenter and Coustan. MAIN OUTCOME MEASURES: Crude and adjusted rates of cesarean delivery and neonatal macrosomia (birth weight >4000 g). RESULTS: Compared with normoglycemic controls, the untreated borderline GDM group had increased rates of macrosomia (28.7% vs 13.7%, P<.001) and cesarean delivery (29.6% vs 20.2%, P=.02). Cesarean delivery in this subgroup was associated with macrosomia (45.5% vs 23.5%, P=.03). Usual care of known GDM normalized birth weights, but the cesarean delivery rate was about 33% whether macrosomia was present or absent. A clearly increased risk of cesarean delivery among treated patients compared with normoglycemic controls persisted after adjustment for multiple maternal risk factors (adjusted odds ratio, 2.1; 95% confidence interval, 1.3 to 3.6). CONCLUSIONS: Infant macrosomia was a mediating factor in high cesarean delivery rates for women with untreated borderline GDM. While detection and treatment of GDM normalized birth weights, rates of cesarean delivery remained inexplicably high. Recognition of GDM may lead to a lower threshold for surgical delivery that mitigates the potential benefits of treatment.     

A protocol of screening of gestational diabetes mellitus

We evaluated GDM frequency in the Padua area. 490 non-diabetic pregnant women were divided into group A (234), with at least one GDM risk factor, and group B (256), with no risk factors. Group A underwent this screening program with oral glucose challenge test (OGCT) and OGTT when OGCT was positive at 10-14th gestational week (gw), at 24-28th gw and at 30-34th gw. Group B underwent the same screening starting at 24-28th gw. 46.9% of the pregnant women had positive OGCT with higher frequency in group A (group A vs group B p < 0.01). GDM prevalence in all women was 10.8% with higher frequency in group A women (group A vs group B p < 0.01). The anticipation of the screening at the first trimester of pregnancy in group A women allowed early diagnosis of 11.6% of GDM. Regarding maternal and fetal outcome the only significative differences between GDM and non-GDM were prevalence of macrosomia and of cesarean sections.     

Cloning and characterization of a mouse homologue (mNthl1) of Escherichia coli endonuclease III

The association patterns between maternal anthropometric characteristics (stature, prepregnancy weight, prepregnancy body mass index, pregnancy weight gain) and newborn size (birth weight, length, head circumference) were tested with 10,240 single births taking place between 1985 and 1995 in Vienna, Austria, and 3,452 single births taking place between 1989 and 1995 in Westerstede-Ammerland (Friesland), northern Germany. Maternal size and newborn size differed highly significantly (p < 0.001) between the two genetically and socioeconomically different population groups. Furthermore, the incidence of macrosomia among newborns (birth weight greater than 4000 g) was extraordinarily high (17.9%) in the Frisian group from northern Germany. In both populations taller and heavier women with a higher weight gain during pregnancy gave birth to heavier offspring. Nevertheless, the pregnancy weight gain, which indicates environmental conditions of the mother, had only a minor impact on newborn size compared with stature and prepregnancy weight, which reflect the maternal genetic potential to a higher degree.     

Insulin sensitivity and insulin response in women with gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is associated with much increased risk of developing diabetes later on in life. Using the frequently sampled intravenous glucose tolerance test and the minimal model analyses we have therefore determined the early insulin response to glucose (EIR) and insulin sensitivity (Si), in women with GDM of different severity (n = 14) and in normal women (n = 10). During the last trimester of pregnancy. GDMs compared to controls had significantly lower EIR (p < 0.001) and Si (p < 0.01). The reduction in EIR was less marked in GDM patients treated with diet alone (n = 6) as compared to GMD patients (n = 8) who subsequently during pregnancy needed treatment also with insulin. The insulin treated GDM group only had higher fasting glucose level than controls (5.2 vs 4.2 mmol/l, p < 0.001). Both GDM subgroups had slightly elevated basal levels of FFA and 3-hydroxybutyrate. Si and EIR were inversely correlated in control women and their fasting glucose correlated both to EIR (r = 0.63, p < 0.05) and to Si (r = 0.59, p < 0.05). In the GDM subgroups Si and EIR were unrelated and there were no correlations between fasting glucose and Si or EIR. These results suggest that glucose intolerance in GDM patients in the last trimester of pregnancy is characterized by both an impaired insulin secretion and an increased resistance to insulin. The impairment of insulin secretion and action increases with the severity of hyperglycemia, and the relative insulin deficiency characterizing GDM patients is associated with a selected defect in insulin action mainly affecting gluco-regulation.     

Impaired endothelium-dependent vasodilatation in women with previous gestational diabetes

OBJECTIVE: To assess whether otherwise healthy women with a history of gestational diabetes mellitus (GDM) may have abnormalities in endothelial function at a very early stage, before glucose intolerance occurs. RESEARCH DESIGN AND METHODS: A total of 33 women with previous GDM (17 nonobese [BMI < 27] and 16 obese [BMI > or = 27]) and 19 healthy nonobese women were examined. A 75-g oral glucose tolerance test was performed, and insulin levels and biochemical parameters were also measured. Using high-resolution ultrasound, we measured vasodilatory responses of the brachial artery during reactive hyperemia (endothelium-dependent vasodilatation), and after nitroglycerin administration, an endothelium-independent vasodilator. RESULTS: Flow-mediated dilatation (FMD) was significantly and equally decreased in both groups of women with previous GDM, compared with control subjects (1.6 +/- 3.7% in the nonobese GDM group and 1.6 +/- 2.5% in the obese GDM group vs. 10.3 +/- 4.4% in control subjects, P < 0.001). FMD correlated inversely with serum uric acid levels, BMI, serum total cholesterol, and basal insulin resistance (homeostasis model assessment). Nitrate-induced dilatation was significantly decreased only in the obese GDM group compared with control subjects, (21.4 +/- 5.1 vs. 27.9 +/- 9.5, P < 0.05). CONCLUSIONS: Endothelial dysfunction, which is considered as a very early index of atherogenesis, is already present in both obese and nonobese women with a history of GDM, even when they have normal glucose tolerance.     

Strobilurin M, tetrachloropyrocatechol and tetrachloropyrocatechol methyl ether: new antibiotics from a Mycena species

OBJECTIVE: To describe lipid and lipoprotein perturbations in gestational diabetes mellitus (GDM) and to examine the potential consequences--e.g, increased birth weight and increased placental lipid transfer. STUDY DESIGN: Maternal and cord free fatty acids (FFAs) and total, very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) (and maternal HDL2 and HDL3), triglyceride (TG), and cholesterol and dietary intake were determined for women with diet-treated GDM and for healthy pregnant women with normal glucose tolerance. RESULTS: Women with GDM had higher hemoglobin A1c than controls, while body weight gain was significantly lower for women with GDM as compared to controls. Plasma and lipoprotein TG concentrations were greater for women with GDM, and although plasma FFAs were higher in women with GDM versus controls, the difference was not significant. No differences were observed between groups with respect to maternal plasma or lipoprotein cholesterol. Cord plasma and lipoprotein lipids were similar between groups; with the exception of VLDL + LDL TG, which was lower in women with GDM. In controls, there were significant correlations between maternal plasma TG and cord FFAs; maternal HDL2 cholesterol and cord plasma cholesterol; and maternal plasma TG, maternal HDL2 cholesterol, cord FFAs, and infant birth weight. In GDM, maternal plasma cholesterol and cord VLDL + LDL cholesterol correlated. There were no significant correlations between maternal or cord lipids and infant birth weight in women with GDM. CONCLUSION: Hypertriglyceridemia, rather than hypercholesterolemia, is a feature of GDM. However, elevations in maternal plasma and lipoprotein TGs in women with GDM were not related to fetal lipid concentrations or infant birth weight.     

Neurophysiologic signal recording. New technical and general practice aspects of EEG recording electrodes

BACKGROUND: The most serious complication of diabetes is the progressive development of vascular changes in which impaired hemocoagulation and fibrinolysis participate. The latter were investigated in diabetes type 1 and 2, but les is known about them in gestational diabetes (GDM). The objective of the submitted work was to assess wither these disorders occur also during GDM and to compare the assessed changes of haemostasis and fibrinolysis with findings in a) non-pregnant healthy controls (n = 58), b) healthy pregnant women (n = 41) and c) groups of pregnant women with impaired haemostasis during gestation/gestational hemorrhage (n = 15), preeclampsia (n = 22), varicosities (n = 15) and dead foetus syndrome (n = 16), but normal carbohydrate metabolism. The changes in GDM were moreover compared with changes found in diabetes type 1 and 2. METHODS AND RESULTS: In pregnant women with GDM (n = 29) which was diagnosed according to WHO criteria the following parameters were examined: number of thrombocytes, APTT, fibrinogen-Fbg (according to Clauss), euglobulin fibrinolysis-ECLT, t-PA concentration, PAI-I (Coaliza, Kabi) and by microturbidimetry the concentration of plasma proteins/orosomucoid (ORM), alpha-1-antitrypsin (A1AT), prealbumin (PREA), transferrin (TRF) and alpha-2-macroglobulin (A2M). In patients with GDM a high Fbg level was found (4.51 +/- 0.98 g/l, p<0.01) not only as compared with Fbg in non-pregnant women (2.42 +/- 0.40 g/l), Fbg in healthy pregnant women (3.63 +/- 0.70 g/l) but also Fg in other patient groups with a pathological pregnancy. In pregnant women with GDM a reduced fibrinolytic activity - ECLT (464 +/- 98 min., p<0.01) was observed as compared with the finding in non-pregnant women (273 +/- 98 min.) but also in healthy pregnant women (303 +/- 106 min.). Another important deviation as compared with findings in healthy pregnant women in GDM is the reduced value of two proteinase inhibitors: A2M (2.04 +/- 0.59 g/l vs. 2.89 +/- 0.90 g/l, p < 0.01) and A1AT (2.98 +/- 0.80 g/l vs. 3.96 +/- 0.85 g/l, p < 0.01). The rise of t-PA (Ag), PAI-1 (Ag), fibrinogen and reduction of fibrinolytic activity (longer ECLT) made the changes the haemostasis and fibrinolysis in GDM closer to findings in DM type 2 than type 1. CONCLUSIONS: In GDM a higher thrombophilia was found (higher Fbg, longer ECLT) than in other groups of pregnant women. Another pathological finding is the reduced A2M level (proteinase inhibitor but also of PDGF and interleukins) and A1AT (inhibitor of leucocytic proteinases). The authors assume that these deviations favour the development of possible vascular changes in GDM and possibly also diabetic foetopathy (reduced A2M).     

Defects in insulin secretion and action in women with a history of gestational diabetes

Gestational diabetes mellitus (GDM) is associated with defects in insulin secretion and insulin action, and women with a history of GDM carry a high risk for the development of non-insulin-dependent diabetes mellitus (NIDDM). Assessment of subjects with a history of GDM who are currently normoglycemic should help elucidate some of the underlying defects in insulin secretion or action in the evolution of NIDDM. We have studied 14 women with normal oral glucose tolerance who had a history of GDM. They were compared with a group of control subjects who were matched for both body mass index (BMI) and waist-to-hip ratio (WHR). All subjects underwent tests for the determination of oral glucose tolerance, ultradian oscillations in insulin secretion during a 28-h glucose infusion, insulin secretion in response to intravenous glucose, glucose disappearance after intravenous glucose (Kg), and insulin sensitivity (SI) as measured by the Bergman minimal model method. The BMI in the post-GDM women was similar to that in the control subjects (24.9 +/- 1.2 vs. 25.4 +/- 1.4 kg/m2, respectively), as was the WHR ratio (0.80 +/- 0.01 vs. 0.76 +/- 0.01, respectively). The post-GDM women were slightly older (35.2 +/- 0.9 vs. 32.1 +/- 1.4 years, P = 0.04). The fasting plasma glucose levels were significantly higher in the post-GDM group than in the control group (4.9 +/- 0.1 vs. 4.4 +/- 0.1 mmol/l, respectively, P < 0.001) and remained higher at each of the subsequent determinations during the oral glucose tolerance test, although none had a result indicative of either diabetes or impaired glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differentiation of BCS-TC2 human colon adenocarcinoma cells by sodium butyrate: increase in 5''-nucleotidase activity

Body mass index (BMI) is the most commonly used measure of obesity. Recently, some investigators have advocated direct measurement of adiposity rather than use of the BMI. This study was undertaken to determine the ability of BMI to predict body fat levels in three populations of West African heritage living in different environments. A total of 1,054 black men and women were examined in Nigeria, Jamaica, and the United States during 1994 and 1995. A standardized protocol was used to measure height, weight, waist and hip circumferences, and blood pressure at all sites; percentage of body fat was estimated using bioelectrical impedance analysis. Percentage of body fat and BMI were highly correlated within site- and sex-specific groups, and the resulting r2 ranged from 0.61 to 0.85. The relation was quadratic in all groups except Nigerian men, in whom it was linear. The regression coefficients were similar across sites, yet the mean body fat levels differed significantly (p < 0.001) as estimated by the intercept, making intersite comparison difficult. Compared with BMI, percentage of body fat was not a better predictor of blood pressure or waist or hip circumference.     

Insulin resistance and essential hypertension in Vietnamese subjects

Several epidemiological and experimental studies suggest that essential arterial hypertension is associated with hyperinsulinism and insulin resistance in obese subjects and also in subjects with normal body weight. Undernutrition remains frequent in adult Vietnamese people and mean body mass index is around 18.5 kg/m2 in Vietnam. The aim of this study was to look for insulin resistance in hypertensive Vietnamese subjects, despite a markedly lower BMI in Vietnam than in occidental countries. One hundred and eight hypertensive patients (51 men and 57 women) over 40 years (mean = 65.4 years) were compared with 36 healthy subjects (23 men and 13 women) over 40 years (mean = 63.8 years). Hypertensive patients had significantly higher BMI (20.5 +/- 0.3 (SEM) kg/m2 vs 18.4 +/- 0.4 kg/m2; p < 0.01), thicker triceps skinfold (1.26 +/- 0.07 cm vs 0.71 +/- 0.07 cm; p < 0.001) and not significantly different waist/hip ratio (0.88 +/- 0.01 vs 0.85 +/- 0.01). Blood glucose at fasting and 2 hours after 75 g glucose taken orally were similar in hypertensive and normotensive subjects. Plasma insulin at fasting and 2 hours after glucose were significantly higher in hypertensive patients (44.4 +/- 5.1 pmol/L vs 21.6 +/- 3.2 pmol/L; p < 0.05 and 271.1 +/- 21.6 pmol/L vs 139.1 +/- 15.2 pmol/L; p < 0.001). Thus, despite under-nutrition, hypertensive Vietnamese patients have a moderate but significant increase in BMI and fat mass without predominant abdominal localization, and a state of insulin-resistance, compared with normotensive healthy subjects.     

Associations between body morphology and bone mineral density in premenopausal women

To investigate whether body morphology, obesity and its long time evolution were associated with lumbar and femoral bone mineral density (BMD) in premenopausal women of the same age. DESIGN: Cross-sectional study. SUBJECTS: 72 healthy premenopausal women born in 1950 (42 years) with a regular physical activity. MEASUREMENTS: BMD measured by dual-X-ray absorptiometry (DEXA) at lumbar spine and proximal femur; body weight, body mass index (BMI), BMI at 20 years (BMI-20), increase in BMI since age of 20 (BMI->20), body circumferences (breast, waist, hip) and their ratios (WHR, BHR, WBR), smoking and alcohol intake. RESULTS: Lumbar spine BMD did not correlate with any anthropometric measurement. Femoral BMDs correlated positively with weight, BMI, BMI-20, breast, waist, WHR and BHR. The BMI-20 explained the 5% and the current BMI the 13% of variance of total femur BMD. After adjustment for weight or BMI, breast circumference and BHR remained significantly correlated with all femoral BMDs sites except neck. Weight was the best predictor for neck BMD (R2 = 0.08; p < 0.02), and BHR for Ward's triangle (R2 = 0.12; p < 0.01) and trochanter (R2 = 0.10; p < 0.001). Alcohol intake, cigarette smoking, and age of menarche were not related to BMDs. CONCLUSION: In premenopausal women of the same age, lumbar spine BMD was not associated with any anthropometric measurement. Greater BHR and its long time of evolution may be determinants of greater femoral BMD (trabecular), whereas body weight may be determinant of femoral neck BMD (cortical). Further studies are needed to determine whether large breast to hip ratio may be considered as a protective factor for femoral osteoporosis.     

History of gestational diabetes leads to distinct metabolic alterations in nondiabetic African-American women with a parental history of type 2 diabetes

OBJECTIVE: Gestational diabetes mellitus (GDM) and positive parental history of type 2 diabetes are predictors of the future development of type 2 diabetes in several populations. However, the relative importance of parental history of diabetes and/or history of GDM as risk factors for the pathogenesis of diabetes in African-Americans remains unknown. Thus, the objectives of the present study were 1) to characterize the glucose homeostatic regulations and 2) to examine the contribution of parental history of type 2 diabetes to the potential metabolic alterations found in nondiabetic African-American women with a history of GDM (HGDM). RESEARCH DESIGN AND METHODS: We evaluated beta-cell secretion, insulin sensitivity (SI), and glucose-dependent glucose disposal (SG) in 15 glucose-tolerant African-American women with a parental history of type 2 diabetes and prior GDM (HGDM) and 35 women with a parental history of type 2 diabetes but without prior GDM (NHGDM). Fifteen healthy nonobese nondiabetic subjects without a family history of diabetes served as control subjects. Body composition was determined by bioelectrical impedance analyzer, and body fat distribution pattern was determined by waist-to-hip ratio (WHR). Insulin-modified frequently sampled intravenous glucose tolerance (FSIGT) test was performed in each subject. SI and SG were determined by the minimal model method. RESULTS: The mean age, BMI, percent body fat content, and lean body mass were not different between the subgroups of relatives with and without a history of GDM, but were greater than those of the healthy control subjects. Mean fasting and postchallenge serum glucose levels were slightly but significantly greater in the HGDM versus NHGDM subjects and the healthy control subjects. However, the 2-h glucose levels were greater in the relatives with and without GDM when compared with the healthy control subjects. In contrast, mean postprandial serum insulin responses were significantly lower between t = 30 and 120 min in the HGDM versus NHGDM groups and the healthy control subjects. The mean serum insulin levels were not different in the NHGDM subjects and healthy control subjects. During the FSIGT test, acute first-phase insulin release (t = 0-5 min) was significantly lower in the HGDM versus NHGDM groups and healthy control subjects. Mean SI was significantly (P < 0.05) lower in the HGDM versus NHGDM subjects and healthy control subjects (1.87 +/- 0.47 vs. 2.87 +/- 0.35 and 3.09 +/- 0.27 x 10(-4).min-1.[microU/ml]-1, respectively). SG was significantly lower in HGDM than NHGDM subjects and healthy control subjects (2.11 +/- 0.15 vs. 3.25 +/- 0.50 and 2.77 +/- 0.22 x 10(-2).min-1, respectively). Mean glucose effectiveness at zero insulin concentrations (GEZI) was significantly lower in the HGDM subjects when compared with the NHGDM and healthy control subjects. CONCLUSIONS: The present study demonstrates that in African-American women with a parental history of type 2 diabetes and GDM, defects in early-phase beta-cell secretion, as well as a decreased SI, SG, and GEZI, persist when compared with those without GDM. We suggest that African-American women with a positive history of GDM have additional genetic defects that perhaps differ from that conferred by a parental history of diabetes alone. Alternatively, the metabolic and hormonal milieu during GDM may be associated with permanent alterations in beta-cell function, SI, and glucose effectiveness in African-American women. These defects could play a significant role in the development of GDM, and perhaps in the subsequent development of type 2 diabetes, in African-American women.     

Decreased stature in gestational diabetes mellitus

Short stature has been associated with various degrees of abnormal glucose tolerance in middle-aged people, where the effects of age and metabolic control would be difficult to exclude. We chose to examine body stature in women with gestational diabetes mellitus (GDM), a prediabetic state affecting a young group of people. A sample of 2772 Greek pregnant women, referred for GDM screening was examined. After a 100-g oral glucose tolerance test, 1787 women were classified as normal (N), 300 women were found with one abnormal glucose value (OAV) and 685 women with GDM. Basal insulin resistance was calculated in 640 women by homeostasis model assessment. In addition, 51 pregnant women with pre-existing Type II (non-insulin-dependent) diabetes mellitus and 109 with pre-existing Type I (insulin-dependent) diabetes mellitus were included in the study. There was a gradual decrease in mean height (cm) as glucose intolerance became more severe: N: 161.0 +/- 6.2, OAV:160.2 +/- 6.1, GDM:158.7 +/- 6.3, Type II diabetes 158.2 +/- 7.0 (p < 0.001, analysis of variance]. Height in Type I diabetes (160.1 +/- 5.9) did not differ from the normal group. The difference in height between the normal and GDM groups remained (p < 0.001) when body weight, age, birth before or after 1960 and educational status were also taken into account. An independent correlation was also found between height and insulin resistance (n = 640) adjusted for the above mentioned variables. In conclusion, short stature appears to be associated with glucose intolerance as an independent variable, even when this intolerance is both mild and temporary. The previously unrecognised independent association of stature with basal insulin resistance merits further investigation.     

Atypical involvement of undifferentiated carcinomas of the nasopharyngeal type. Apropos of 3 cases

This study compared body sway, a measure of postural stability, between regular brisk walkers and control subjects. Furthermore, the relationship between body sway and physical activity duration in postmenopausal women was examined. Subjects were 31 healthy postmenopausal women, aged 61-71 years. They were recruited from a randomized controlled study of the influence of brisk walking on bone: 16 women had been completing 20 min d-1 brisk walking, whilst 15 controls had been completing habitual activities only. Body sway was measured using a swaymeter that measured displacement at the waist whilst subjects stood on a compliant surface, with eyes closed, for 1 min. The activity was measured using activity monitors which were worn at the waist for 3 consecutive days. Body sway (eyes closed, standing on a compliant surface) was lower in walkers than in controls: 2,958 +/- (SE) 270 versus 5,225+/-371 mm2 min-1, respectively (p < 0.05). A negative correlation was found between body sway and minutes of physical activity (r = -0.47, p < 0.01). Analysis of variance revealed that body sway differed significantly (p < 0.05) between groups of differing physical activity participation, being 4,839 +/- 499, 4,167 +/- 516, and 2,877 +/- 362 mm2 min-1, respectively, in women completing <20, 20-40, and >40 min d-1 of physical activity. Body sway was significantly lower in the most active group than in the least active (p < 0.01). These data suggest that postural stability is better in regular walkers than in control subjects. Furthermore, a dose-response relationship was observed between physical activity and postural stability in postmenopausal women. These findings provide a preliminary indication that brisk walking, a low-cost and acceptable form of physical activity for the elderly, could be incorporated into strategies for improving balance in the elderly.     

Thyroid hormones modulate serum leptin levels: observations in thyrotoxic and hypothyroid women

Thyroid hormones and leptin are both involved in the regulation of energy metabolism. Serum leptin concentrations were measured in women with thyrotoxicosis (n = 21, mean age 45 years) or hypothyroidism (n = 14, mean age 44 years) before and 3 months after restoration of the euthyroid state. Serum leptin concentration tended to increase in both hypothyroid (14.7+/-3.5 vs 17.8+/-3.9 ng/ml, p = 0.06) and thyrotoxic (11.9+/-1.7 vs 14.4+/-2.0, p = 0.08) women after treatment (values given as mean +/- SE in the untreated and the euthyroid state respectively). Body mass index (BMI) was lower in thyrotoxic women than in hypothyroid women in the untreated state (22.1+/-0.7 vs. 26.2+/-1.9, p < 0.05). BMI was not different between both groups after treatment (24.5+/-0.7 vs. 26.3+/-2.1, p = 0.37), due to an increase of BMI in the thyrotoxic women; BMI did not change in the hypothyroid group. After controlling for BMI in a multivariate regression analysis, serum leptin concentrations were lower in hypothyroid women than in thyrotoxic women (p < 0.05), whereas posttreatment values of leptin did not differ (p = 0.44). When leptin concentrations were expressed as standard deviation scores (Z-scores) from the mean value of female controls matched for BMI and age as reported earlier, Z-scores were lower in the hypothyroid than in the thyrotoxic women (-0.63+/-0.21 vs. 0.53+/-0.18, p = 0.001). After treatment, Z-scores did not deviate from the expected values (0.05+/-0.28 vs. 0.08+/-0.16, p = 0.98). Z-scores differed before and after treatment in both hypothyroid (p = 0.01) and thyrotoxic (p = 0.02) patients. In conclusion, these data obtained in thyrotoxic and hypothyroid women indicate that thyroid states modulates serum leptin concentrations independent of BMI, with a small decrease in hypothyroidism and a small increase in thyrotoxicosis.     

Glycosylated hemoglobin and fetal growth in normal, gestational and insulin dependent diabetes mellitus pregnancies

Aims of the study were: evaluation of HbA1c levels in the peripheral blood of pregnant women with insulin dependent diabetes, gestational diabetes, glucose intolerance, and healthy pregnant controls; implications of HbA1c concentration on detection and the control of women with impaired carbohydrate metabolism in pregnancy; comparison of HbA1c levels with appearance of miscarriages, and premature deliveries; comparison of weight gain during pregnancy to HbA1c levels; comparison of difference from ideal body weight with HbA1c in diabetic pregnant women; comparison of neonatal birth weight and HbA1c levels. 290 pregnant women were enrolled to the study. The highest value of HbA1c was in the group IDDM pregnant women (7.7% +/- 1.8%), and the lowest value of HbA1c was in the control group (4.1% +/- 0.5%). Statistically significant coefficients were found between HbA1c and weight gain during pregnancy, between weight deviation from ideal body weight and HbA1c (r = 0.54 and r = 0.48 respectively); and between newborns weight and HbA1c (r = 0.51). Well regulated glycemia and intensive pregnancy follow-up of diabetic women reduces stillbirths, neonatal complications and neonatal macrosomia incidence.     

Effects of pneumoperitoneum with carbon dioxide, argon, or helium on hemodynamic and respiratory function

In this study we investigated ob gene expression and plasma leptin levels in Psammomys obesus (the Israeli Sand Rat), a polygenic animal model of obesity and non-insulin-dependent diabetes mellitus. The ob gene was expressed exclusively in adipocytes of Psammomys obesus. DNA sequencing revealed a high degree of homology with other species (90% with mouse, 88% with rat and 79% with human). No ob gene sequence differences were found between lean and obese Psammomys obesus, and the codon 105 mutation found in ob/ob mice was not detected. Ob gene expression in Psammomys obesus correlated with body weight (r = 0.436, p < 0.001), percent body fat (r = 0.645, p < 0.001) and plasma insulin concentration (r = 0.651, p < 0.001). This is the first time that ob gene expression has been shown to increase steadily over a continuous wide range of body weight or plasma insulin in an animal model of obesity. Ob gene expression was significantly elevated in obese compared with lean Psammomys obesus (p < 0.05). No significant difference in ob gene expression was found between the four adipose tissue depots tested. Psammomys obesus plasma leptin levels correlated with body weight (r = 0.36, p < 0.05), percent body fat (r = 0.702, p < 0.01) and plasma insulin concentration (r = 0.735, p < 0.001). Plasma leptin concentrations were significantly increased in insulin-resistant animals independent of body weight. These results show that Psammomys obesus is an excellent animal model in which to study the ob gene and leptin, and confirm the importance of insulin as a significant factor in the regulation of leptin and ob gene expression.     

Treatment system for drug-dependence syndrome

OBJECTIVE: There is emerging evidence that women with visceral obesity may have hyper-responsiveness of the hypothalamic-pituitary-adrenal axis. There are no studies on basal daily secretory pattern of ACTH and cortisol in subjects with different obesity phenotypes. DESIGN AND PATIENTS: In this study we examined daytime pulsatile secretion of ACTH and cortisol in two groups of premenopausal obese women with visceral (V-BFD) (BMI 37.1 +/- 1.7) and subcutaneous (S-BFD) (BMI 38.8 +/- 1.5) body fat distribution (measured by CT scan) and in a group of normal weight healthy controls (BMI 21.1 +/- 0.5). After an overnight fast, blood samples were taken at 15-minute intervals for 12 h (49 samples, from 0800 h until 2000 h). All women avoided breakfast but had a normal lunch and dinner, both containing similar food, energy and nutrient composition. ACTH and cortisol responses to mixed meals at noon and in the evening were also investigated. RESULTS: Mean values of ACTH and cortisol did not differ between the groups. However, ACTH pulse frequency was significantly higher in V-BFD (P < 0.06) and S-BFD (P < 0.02) obese women than in controls, without any significant differences between the two obese subgroups. Mean ACTH pulse amplitude was lower in the V-BFD than in S-BFD obese (P < 0.02) and control (P < 0.05) groups. Cortisol episodic characteristics did not differ between V-BFD and S-BFD obese and controls. All differences in ACTH pulsatile parameters between obese and controls and between the two obese subgroups were evident only in the morning, with no further significant differences during the early and late afternoon. There were no significant differences in cortisol parameters during the three periods of the day between the various groups, apart from late afternoon cortisol pulse frequencies, which were significantly lower in V-BFD than in controls. After lunch, ACTH and cortisol levels significantly increased in all groups, but the cortisol increase tended to be more rapid in V-BFD than in the other two groups. After dinner, ACTH significantly increased in V-BFD and controls but not in the S-BFD group, whereas cortisol rose significantly in all groups, but significantly less in S-BFD than in V-BFD and controls. CortisolAUC (but not ACTHAUC) after lunch was significantly higher than after dinner in all groups. ACTH response after each meal was similar in all groups, but cortisolAUC after dinner was significantly lower in S-BFD than in V-BFD women. CONCLUSION: This study demonstrates that in premenopausal women, obesity, particularly the visceral phenotype, is associated with several abnormalities of ACTH pulsatile secretion, particularly in the morning. On the contrary, no major differences were present in either blood concentrations, diurnal rhythm or secretory pattern of cortisol between obese and controls. The responses to meals seem to indicate a much more rapid cortisol response after lunch in women with visceral obesity and a reduced activation of the hypothalamic-pituitary-adrenal axis after dinner in women with subcutaneous obesity.     

The establishment of a three dimensional PCR screening system and quality evaluation of human YAC library

To determine whether pregnancy provides an improved milieu for fetal/neonatal pancreas/islet transplantation, we studied neonatal pancreatic implants into non-obese diabetic (NOD) female mice during early gestation. We monitored maternal glycemic status, birthweight of the offspring, and graft histology to assess the efficacy of transplantation. One hundred and thirteen twelve-week-old NOD female mice were randomized into four groups as follows: (1) non-pregnant NOD mice received a sham operation; (2) non-pregnant NOD mice received neonatal pancreatic transplants; (3) pregnant NOD mice received a sham operation; and (4) pregnant NOD mice received neonatal pancreatic transplants. Pancreas segments from 3 neonatal NOD mice were placed via an incision 1 to 2 mm distal to the ear-skull junction of each of the recipients. Maternal blood glucose and glycated hemoglobin were determined between days 18 and 20 after the surgery. Pups were weighed within 5 to 6 hours after delivery. Pregnant NOD that received transplants (n = 29) had lower glucose and glycated hemoglobin (GHb) than sham operated pregnant controls (n = 26) (4.9 +/- 0.05 versus 9.0 +/- 5.0 mmol/L, p < 0.001 for glucose and 2.0 > or = 0.2 versus 3.0 > or = 1.2%, p < 0.008 for GHb) at 18 to 20 days of gestation. Controlling for litter size showed a decrease in birthweight for offspring of transplant recipients versus offspring of pregnant controls (1.59 +/- 0.08 versus 1.65 +/- 0.08 g, p < 0.002). Histological scoring of transplanted tissue at day 21 indicated that the lymphocytic infiltration in the pregnant group was significantly less than the control group (2.9 +/- 1.2 versus 4.9 +/- 0.2, p < 0.0001). We conclude that the pregnant NOD mouse provides a useful transplant model, that pregnancy provides an opportunity to increase beta-cell mass with transplanted tissue, and that pancreatic transplantation decrease birthweight and macrosomia in the offspring of NOD mice.