Ambulatory blood pressure as predictor of preeclampsia in diabetic pregnancies with respect to urinary albumin excretion rate and glycemic regulation

BACKGROUND: Twenty-four-hour ambulatory blood pressure was evaluated as a predictor of preeclampsia in women with insulin-dependent diabetes mellitus with respect to urinary albumin excretion rate and glycemic regulation. METHODS: One hundred and fifty-one women with insulin-dependent diabetes mellitus were consecutively recruited from the outpatient maternity ward for 24 hour ambulatory blood pressure measurement with a portable monitor (SpaceLab 90207). Blood pressure was measured three times during pregnancy and once after delivery. Evaluation was performed with receiver-operator-characteristics curves in primiparous women. Stratified analysis and multiple regression was applied with respect to urinary albumin excretion rate, HbA1c, age, duration of diabetes mellitus, uric acid, and BMI. RESULTS: The incidence of preeclampsia was significantly associated with increasing urinary albumin excretion rate, primiparity, and ambulatory blood pressure. Ambulatory blood pressure was associated with HbA1c throughout pregnancy adjusted for urinary albumin excretion rate. The ambulatory blood pressure was higher from first trimester throughout pregnancy in women developing preeclampsia compared to women who did not have preeclampsia. The best sensitivity and specificity for predicting preeclampsia in primiparous women were at cut-off values of systolic and diastolic day ambulatory blood pressure above 122 and 74 mmHg, respectively. The relative risk of preeclampsia was significantly higher when ambulatory blood pressure was above the cut-off values and increased further with higher urinary albumin excretion rate. CONCLUSIONS: The relationship between ambulatory blood pressure and preeclampsia is not confined to women with macroalbuminuria but is also present in women with normo- and microalbuminuria. Poor glycemic control and increased urinary albumin excretion rate is associated with preeclampsia when ambulatory blood pressure is above cut-off values of 122/74 mmHg (systole/diastole). Ambulatory blood pressure is a reliable measurement for prediction of preeclampsia in primiparous women with insulin-dependent diabetes mellitus.     

Increased soluble VCAM-1 serum levels in preeclampsia are not correlated to urinary excretion or circadian blood pressure rhythm

OBJECTIVE: Soluble vascular cell adhesion molecule-1 (VCAM-1) is known to be elevated in serum of patients with preeclampsia, but there are no data available on the significance of urinary VCAM-1 excretion in preeclampsia. The aim of our study was to uncover possible circadian rhythms of VCAM-1 plasma levels and urinary VCAM-1 excretion in uncomplicated and hypertensive pregnancies and to ascertain their relation to blood pressure. STUDY DESIGN: A total of 10 normotensive and 10 preeclamptic pregnant women were included in this study. Venous blood was collected hourly, and urine samples were taken every 2 h over a period of 24 h. VCAM-1 levels were determined by ELISA. We compared these results with the circadian blood pressure rhythm. RESULTS: The median VCAM-1 plasma levels were significantly (P < 0.01) increased in preeclamptic patients (851.5 ng/mL) in comparison to normotensive pregnant women (659.3 ng/mL) without any circadian rhythm being apparent; however, the urinary excretion of VCAM-1 showed a typical circadian rhythm, with a higher excretion rate during daytime. CONCLUSION: For the first time we have demonstrated that urinary VCAM-1 excretion in pregnancy shows a circadian rhythm without correlation to plasma levels or the circadian blood pressure rhythm. In contrast, VCAM-1 serum levels did not show a diurnal rhythm. We assume that VCAM-1 serum levels do not correlate with systemic blood pressure or urinary excretion.     

Gestational Diabetes: Glycemic Control in the Last Two Weeks Before Delivery Contributes to Newborn Insulinemia

Introduction

Fetal hyperinsulinemia in gestational diabetes mellitus (GDM) not only is important during intrauterine life, a time when it can result in macrosomia, but also at delivery, since it can result in neonatal hypoglycemia and hyperbilirubinemia. The question is, how long before delivery does maternal glycemic control contribute to newborn insulinemia in GDM?

Acute Caffeine Ingestion and Glucose Tolerance in Women With or Without Gestational Diabetes Mellitus

ObjectiveRecent work showing that caffeine impairs glucose tolerance may be of particular concern in pregnancy because of a possible negative effect on fetal outcome. The current study sought to assess the effect of acute caffeine ingestion on glucose tolerance in women with or without gestational diabetes mellitus (GDM).MethodsNineteen women whose routine GDM test was negative (control) and eight women with an initial positive GDM screen completed two trials one week apart in a double-blind randomized crossover study. Following an overnight fast, subjects ingested caffeine (3 mg/kg pre-pregnancy body weight) or an identical-appearing placebo (gelatin) capsule and one hour later began a 75 g 2-hour oral glucose tolerance test.ResultsIn the control group, caffeine did not significantly affect blood glucose, insulin, or C-peptide. In the GDM group, glucose area under the curve (AUC) was greater (P < 0.01), C-peptide AUC was greater (P < 0.05), and insulin sensitivity index was lower (18%, P < 0.05) after caffeine than after placebo.ConclusionCaffeine impaired insulin sensitivity in women with GDM. Additional research regarding more specific dietary caffeine recommendations for women with GDM is warranted.     

Relationship of maternal glycosylated hemoglobin and fetal beta-cell activity with birth weight

A population of 40 mother-newborn pairs with a wide range of birth weight has been studied. Seventeen of the mothers were diabetic, while the other 23 were normal pregnant women. The chronic blood glucose levels were assessed in the mothers through the percentage of glycosylated hemoglobin (HbA1) at delivery. The functional activity of the pancreatic beta-cells in the newborns was estimated through the concentration of insulin and C-peptide in the cord blood. Maternal HbA1 was not quantitatively related to the birth weight ratio. In contrast, both insulin and C-peptide correlated significantly with it. Is is concluded that in populations with a good metabolic control, blood glucose levels, as measured by HbA1, are not the major determinant of fetal growth.     

Evaluation of insulin resistance and metabolic syndrome in patients with polycystic ovary syndrome

Aim.?Polycystic ovary syndrome (PCOS) is associated with the clustering of states including insulin resistance (IR), obesity, elevated blood pressure, and dyslipidemia that are termed as metabolic syndrome (MBS). This study was designed to assess the differences between homeostatic model assessment (HOMA) values in PCOS and healthy women.

Methods.?In a case–control study, 55 women with PCOS and 59 women with normal cycles (control group) aged 15–40 years old were evaluated. In all the subjects (after obtaining written informed consent), blood pressure, body weight, height, body mass index (BMI), waist /hip ratio(WHR) and fasting blood glucose (FBG), triglycerides (TG), HDL, C-peptide, insulin, HOMA Index, and FGIR (fasting glucose to insulin ratio) were measured.

Results.?In this study, the prevalence of MBS was significantly higher in PCOS group compared with the control group (p = 0.028). There were no significant differences in age, waist/hip ratio, fasting glucose, insulin, and C-peptide levels between patients with PCOS and control group. Furthermore, the prevalence of impaired fasting glucose (IFG) and the mean of HOMA and FGIR did not differ significantly between PCOS and control group.

Conclusion.?Criteria of MBS are frequently present in young women with PCOS and may be more useful as a prognostic factor than IR indexes in this age group. We suggest evaluation of IR in older age women with PCOS.     

Hirsute women with elevated androgen levels: Psychological characteristics,steroid hormones,and catecholamines

Fifteen hirsute women with oligomenorrhea were compared with age-matched, healthy, normally menstruating women during rest and experimentally induced stress to explore the relation between increased androgen levels and catecholamine excretion. Testosterone levels in serum (p<.0001) and basal catecholamine excretion (p<.05) were higher in hirsute women than in the control group. Testosterone levels of hirsute women were negatively correlated with serum Cortisol (p<.05) and urinary Cortisol (p<.01) levels. No significant correlations were found between urinary catecholamines and serum steroid hormone or urinary Cortisol levels. The control group responded to the experimentally induced stress with an increase in diastolic blood pressure (p<.001). In the personality measurements, the hirsute women scored higher than the control subjects as to introversion, anxiety proneness, psychasthenia, guilt, and inhibited aggression. They were more anxious to please others, and experienced a lack of control over personal life events, but did not differ as to self-reported masculinity-femininity.     

Simplification of continuous infusion of glucose with model assessment in the evaluation of insulin resistance in women with PCOS.

Ninety-seven women with polycystic ovary syndrome (PCOS) were tested for insulin resistance and glucose tolerance by means of the continuous infusion of glucose with model assessment (CIGMA) test. The mean concentrations of glucose and insulin at 50, 55 and 60 min of glucose infusion were interpreted using a mathematical model of glucose and insulin homeostasis, and an insulin resistance index (IR1) was obtained. Using insulin and glucose values at 60 min only, a new insulin resistance index (IR2) was obtained using the same mathematical method. In addition, fasting insulin, fasting C-peptide, fasting glucose, fasting insulin:glucose ratio and fasting C-peptide:glucose ratio were also used to assess insulin resistance. There were significant correlations between IR1 and IR2, fasting glucose, fasting insulin, fasting insulin:glucose ratio, fasting C-peptide:glucose ratio. IR2 had the highest correlation with IR1 (r = 0.97, p < 0.001) and provided the best combination of sensitivity (82.9%), specificity (93.9%), positive predictive value (91.9%) and negative predictive value (86.8%). In conclusion, the simplified CIGMA test, using insulin and glucose concentration at 60 min of glucose infusion only, is a highly sensitive and specific measure of insulin sensitivity in women with PCOS.     

Urinary iodine excretion and thyroid function in pregnant women of Bydgoszcz District prior to and after the introduction of iodized salt

INTRODUCTION: Before the introduction of the kitchen iodized salt in 1997 Poland was an area of mild and moderate iodine deficiency. AIM: The aim of the study was to determine the degree of iodine deficiency and thyroid function in pregnant women prior to and after the introduction of iodized salt. MATERIAL AND METHODS: Iodine urinary excretion and serum levels of TSH, fT3 and fT4 were determined in pregnant women divided into the two groups--with and without iodine supplementation. RESULTS: Before the introduction of the kitchen iodized salt iodine urinary excretion in pregnant women was 70.46 +/- 43.99 micrograms/l. The introduction of kitchen iodized salt increased iodine urinary excretion to 92.23 +/- 42.14 micrograms/l (p < 0.01). In pregnant women with iodine supplementation serum levels of TSH and fT3 were reduced. CONCLUSIONS: 1. There was a mild iodine deficiency in pregnant women before the introduction of the kitchen iodized salt programme. 2. The kitchen iodized salt increased iodine urinary excretion rates, 3. Reduced levels of serum TSH and fT3 after the introduction of iodized salt indicate diminished thyroid stimulation in pregnant women with higher iodine intake.     

Kidney function in pregnant women with hypertension in the course of chronic kidney disease]

In 53 pregnant patients in the III trimester of pregnancy kidney function investigations were carried. The group consisted of 23 patients with chronic kidney diseases with superimposed arterial hypertension (examined group) and of 30 healthy pregnant women (control group). In the examined group an increase of blood-serum urea, uric acid and creatinine concentrations were demonstrated. In these women the blood pH was decreased also. The urinary excretion of NH4+ and H+ ions was decreased, the excretion of Na+ and K+ was normal.     

The influence of short-term estrogen replacement therapy (ERT) on the blood pressure and daily urinary catecholamine excretion in a small group of post-menopausal women

The blood pressure and daily urinary catecholamine excretion were examined in nineteen non-smoking post-menopausal women, receiving estrogen replacement therapy for a period of 4 months. The estrogens administered consisted of 17 beta-estradiol combined with estriol and norethisterone acetate administered sequentially (Trisequens, Novo, Denmark). Before the institution of treatment, the blood pressure and urinary catecholamine excretion were normal. After a period of 4 months, no change in blood pressure was observed. However, a marked and significant increase in daily urinary catecholamine excretion was noticed (72.3 +/- 18.96 micrograms/day to 102.0 +/- 26.0 micrograms: p less than 0.01). The pathogenetic implications of this increase are discussed.     

Various biochemical parameters of renal tubular function in patients with type I diabetes in the third trimester of pregnancy

The studied group comprised 47 women in the 3rd trimester of pregnancy (29-40 weeks), including 17 with type I diabetes (study group) and 30 healthy women (control group). In the study group in one case diabetes was diagnosed during pregnancy and treated with diet only, in the remaining 16 pregnant women the mean diabetes duration was 6.2 years and the mean daily insulin dose was 70 u. According to White's classification one patient was in class A, 10 in class B and 6 in class C. In all cases renal function was normal, with normal blood values of creatinine, urea, electrolytes, uric acid, protein and acid-base equilibrium. Endogenous creatinine clearance was also normal. The studied biochemical parameters of renal tubular function included: 1) deamination of amino acids--with measurement of ammonium ion (NH4+) excretion with urine, 2) carbonic acid metabolism--with determination of urinary excretion of hydrogen ions (H+), 3) urinary excretion of sodium (Na+) and potassium (K+) ions. Besides that 24-hour urine was always measured. The studied women were similarly hydrated (standard diet, fluid balance control). The results were subjected to statistical analysis. In women with type I diabetes the volume of 24-hour urine was increased, although it fell within the normal range, urinary excretion of Na+ and K+ was raised. No change was found in amino-acid deamination an carbonic acid metabolism since the excretion of NH4+ and H+ was normal.     

Magnesium supplementation to prevent high blood pressure in pregnancy: a randomised placebo control trial

Purpose

To assess if hypertension during the last part of pregnancy could be prevented by magnesium supplementation.

Methods

Pregnant primagravida women from a local antenatal care unit were given an oral supply of 300 mg magnesium as citrate or placebo from pregnancy week 25 in a randomised double-blind setup. Blood pressure was recorded during pregnancy as well as pregnancy outcome.

Results

In the magnesium-supplemented group, the average diastolic blood pressure at week 37 was significantly lower than in the placebo group (72/1.4 mean/SEM vs 77/1.4, p = 0.031). The number of women with an increase in diastolic blood pressure of ≥15 mmHg was significantly lower in the magnesium group compared with the women who received placebo (p = 0.011). There was an inverse relation between the urinary excretion of magnesium during pregnancy and the diastolic blood pressure (p = 0.005).

Conclusions

Magnesium supplementation prevented an increase in diastolic blood pressure during the last weeks of pregnancy. The relation between diastolic blood pressure and urinary excretion of magnesium suggests that magnesium is involved in the regulation of blood pressure and that the increase in diastolic blood pressure in pregnancy could be due to a lack of magnesium.     

Effects of a low-dose estrogen-antiandrogen combination (Diane-35) on lipid and carbohydrate metabolism in patients with polycystic ovary syndrome

This study was undertaken in order to evaluate the effect of an oral contraceptive containing 35 micrograms of ethinyl estradiol and 2 mg of cyproterone acetate (Diane-35) on carbohydrate and lipid metabolism in patients with polycystic ovary syndrome (PCOS). Twenty three patients with PCOS were treated with Diane-35 for between 9 and 18 cycles without interruption (a total of 318 treated cycles). Metabolic evaluations, which included measurements of fasting blood glucose, insulin, C-peptide, total cholesterol, triglyceride, total lipids, HDL-cholesterol, LDL-cholesterol and apolipoproteins (Apo A1, Apo A2 and Apo B), were performed before treatment and every 3rd cycle during the treatment period. In the case of 5 women an oral glucose tolerance test (oGTT) was performed before and after the 12th cycle of Diane-35 treatment, with blood samples taken for glucose, insulin and C-peptide measurements. Total cholesterol showed a significant increase after the 6th cycle (p less than 0.001) and reached the mean maximal value after the 9th cycle. A similar increasing trend was observed with LDL-cholesterol, which also reached the maximal mean level after the 9th cycle of treatment (p less than 0.05). There were no significant changes in HDL-cholesterol levels. Significant increases in serum triglyceride (p less than 0.01) and total lipids (p less than 0.001) were observed after the 3rd cycle. Apo A2 concentrations increased significantly after the 6th cycle (p less than 0.001) and showed an increasing trend thereafter. A significant increase was also observed in Apo B concentrations after the 6th cycle but these decreased after the 12th cycle. In spite of these observed increases in serum lipids and lipoproteins, the mean levels remained within the normal range throughout the treatment period. Fasting serum glucose, insulin and C-peptide concentrations did not show any significant changes during the study. Higher insulin and C-peptide responses during the oGTT were observed after the 12th cycle but the differences in the areas under the curve before and after treatment were not significant. A deterioration of blood glucose was observed after treatment with Diane-35, a significant difference in mean values being noted 150 minutes after the glucose overload (p less than 0.005). However, the areas under the curve in blood glucose response before (34.92 +/- 4.12) and after (43.45 +/- 3.61) treatment were not significantly different.(ABSTRACT TRUNCATED AT 400 WORDS)     

Simplification of continuous infusion of glucose with model assessment in the evaluation of insulin resistance in women with PCOS

Ninety-seven women with polycystic ovary syndrome (PCOS) were tested for insulin resistance and glucose tolerance by means of the continuous infusion of glucose with model assessment (CIGMA) test. The mean concentrations of glucose and insulin at 50 ,55 and 60 min of glucose infusion were interpreted using a mathematical model of glucose and insulin homeostasis ,and an insulin resistance index (IR₁) was obtained. Using insulin and glucose values at 60 min only ,a new insulin resistance index (IR₂) was obtained using the same mathematical method. In addition ,fasting insulin ,fasting C-peptide, fasting glucose ,fasting insulin : glucose ratio and fasting C-peptide : glucose ratio were also used to assess insulin resistance. There were significant correlations between IR₁ and IR₂, fasting glucose ,fasting insulin ,fasting insulin : glucose ratio ,fasting C-peptide : glucose ratio. IR₂ had the highest correlation with IR₁ (r =0.97 ,p < 0.001) and provided the best combination of sensitivity (82.9%) ,specificity (93.9%) ,positive predictive value (91.9%) and negative predictive value (86.8%). In conclusion ,the simplified CIGMA test ,using insulin and glucose concentration at 60 min of glucose infusion only ,is a highly sensitive and specific measure of insulin sensitivity in women with PCOS.     

Amino acid concentrations in maternal plasma and amniotic fluid in relation to fetal insulin secretion during the last trimester of pregnancy in gestational and type I diabetic women and women with small-for-gestational-age infants

Free amino acid concentrations were determined in maternal plasma and amniotic fluid (AF) under standardized and unstressed conditions in four groups of women comprising 6 gestational and 13 type I diabetics, 10 women with small-for-gestational-age (SGA) infants, and 18 healthy control women between 36 and 39 weeks of gestation. Plasma values for branched chain amino acids (the sum of leucine, isoleucine and valine) did not differ significantly between the four groups. The corresponding values in AF were significantly higher (P less than 0.05) in the type I diabetic group and significantly lower (P less than 0.05) in the gestational diabetic group as compared to the control group. The mean AF C-peptide concentration was elevated but not significantly so in gestational (0.69 nmol/l) or type I diabetic (0.54 nmol/l) pregnancies and significantly lower (P less than 0.05) in women with SGA infants (0.28 nmol/l) as compared to the control group (0.38 nmol/l). There was a significant correlation between C-peptide in AF and branched chain amino acids in maternal plasma (r = 0.63; P less than 0.05) as well as to maternal blood glucose (r = 0.79; P less than 0.01) in the type I diabetic group, which merely suggests a greater beta cell reactivity to insulin secretagogues in offspring of diabetic mothers. The correlation between AF C-peptide and branched chain amino acids in maternal plasma was significantly inverse in women with SGA infants (r = -0.75; P less than 0.05). Both individual, branched chain, or total amino acid concentration in AF were unrelated to AF C-peptide.     

Pyridoxine treatment of chemical diabetes in pregnancy.

Thirteen women with chemical diabetes diagnosed in late pregnancy were found to excrete excessive amounts of urinary xanthurenic acid after a tryptophan load, indicative of a relative pyridoxine (vitamin B6) deficiency. Treatment with 100 mg pyridoxine daily for 14 to 23 days restored the urinary xanthurenic acid excretion to normal in all patients. Improvement of glucose tolerance was observed in only two of the patients studied, deterioration in six, and no significant change in the remaining five. The insulin response to glucose was unaltered during pyridoxine therapy.     

GDM孕中、晚期及子代胰岛素抵抗与正常妊娠的对照研究

目的探讨妊娠期糖尿病(GMD)与正常妊娠孕中、晚期及子代胰岛素抵抗、胰岛β细胞功能及胎儿脐血流的差异。方法选择上海交通大学医学院附属国际和平妇幼保健院产检、分娩的70例GDM产妇及其子代为GDM组,同期产检、分娩的70例健康母子配对样本为对照组。两组孕妇孕24~28周OGTT筛查时行胰岛素释放试验、孕33~34周、孕37~38周检测空腹血糖、胰岛素及C肽;比较两组稳态模型评估的胰岛素抵抗指数(HOMA-IR);B超测定孕晚期胎儿脐血流;分娩时检测脐血血糖、胰岛素及C肽值并获取胎儿出生体重、胎龄等资料;比较两组母子配对样本间各项指标的差异。结果 GDM组OGTT时胰岛素峰值较对照组延迟1h;GDM组孕33~34周母血空腹胰岛素、C肽高于对照组,差异有统计学意义(P<0.05);孕37~38周母血空腹胰岛素、C肽虽仍高于对照组,但差异无统计学意义(P>0.05);GDM组孕中、晚期HOMA-IR高于对照组,差异有统计学意义(P<0.05);GDM组新生儿脐血胰岛素、C肽高于对照组,差异有统计学意义(P<0.05);两组间孕晚期胎儿脐动脉S/D值、搏动指数(PI)、阻力指数(RI)比较差异无统计学意义(P>0.05)。结论 GDM患者孕中、晚期胰岛素抵抗较正常孕妇增加,并出现胰岛β细胞功能下降,其胎儿在宫内已发生糖代谢异常,但脐血流未受到显著影响。     

Urinary tissue kallikrein excretion in black African women with severe pre-eclampsia

BACKGROUND: A study of tissue kallikrein excretion in African women with severe pre-eclampsia. METHODS: Random untimed urine samples were collected from all women (n=198) recruited to this study; 66 women with severe pre-eclampsia, 66 normotensive pregnant women of similar length of gestation and 66 normotensive non-pregnant women. Urine specimens were analyzed for urinary tissue kallikrein using a selective, synthetic chromogenic tripeptide substrate (S2266) having the sequence H-D-Val-Leu-Arg-pNA. RESULTS: Urinary tissue kallikrein levels were decreased in women with severe pre-eclampsia compared with those of gestation matched normotensive pregnant women at 28 weeks of gestation (1.55+/-0.95 vs. 3.02+/-1.35 ng TK/microg protein; p<0.0001) and at near delivery date (1.21+/-0.53 vis. 3.11+/-1.2 ng TK/microg protein; p<0.0001). In the normotensive pregnant group, there was no significance difference in urinary tissue kallikrein excretion close at delivery date compared to 28 weeks of gestation (3.02+/-1.35 vs. 3.11+/-1.21 ngTK/microg protein; p=0.23). No statistical difference in urinary tissue kallikrein excretion was observed between normotensive pregnant and normotensive non pregnant women (3.02+/-1.35 vs. 2.97+/-1.12 ngTK/microg protein; p=0.16). Urinary tissue kallikrein excretion correlated positively with urinary creatinine levels at 28 weeks of gestation (r=0.69; p<0.0001) and close to delivery date (r=0.84; p<0.0001). There was no correlation between neonatal birthweight and urinary tissue kallikrein levels (r=-0.44; p=0.41). CONCLUSION: The decreased levels of urinary tissue kallikrein excretion in pre-eclamptic patients suggests an etiological role for this serine protease in hypertensive disorders of pregnancy.     

The influence of abnormal glucose tolerance (hyperglycaemia and hypoglycaemia) on pregnancy outcome when oestriol excretion is subnormal.

Subnormal urinary oestriol excretion was present in 611 (13.9 per cent) of 4403 consecutive patients in whom a glucose tolerance test had been performed and urinary oestriol excretion measured during the third trimester of pregnancy. Hypoglycaemia (less than 5th centile) had a significant association with subnormal oestriol excretion. The perinatal mortality rate was significantly higher in the presence of abnormal glucose tolerance when oestriol excretion was low. Normoglycaemia was associated with a perinatal mortality rate of 1.7 per cent when oestriol excretion was persistently low, whereas in the presence of hyperglycaemia (greater than 95th centile) the perinatal mortality rate was 12.5 per cent (P less than 0.01) and when there was hypoglycaemia the rate was 14.8 per cent (P less than 0.001). Small-fordates babies occurred in 46.3 per cent of pregnancies complicated by hypoglycaemia and persistently subnormal urinary oestriol excretion. The advantage of routine urinary oestriol assay and glucose tolerance testing in pregnancy is emphasized.