Serum leptin levels in pregnant women with type 1 diabetes mellitus.

BACKGROUND: Leptin is an important weight regulator and during pregnancy leptin is not only synthesized in adipose tissue but also in the placenta. AIM: To examine changes in serum leptin levels in women with type 1 diabetes mellitus during pregnancy and post delivery in relation to concomitant changes in maternal body weight, birth weight, glycemic control, and blood pressure. METHODS: Non-fasting serum leptin from 45 women with type 1 diabetes mellitus were studied consecutively throughout pregnancy and 3 months post partum. RESULTS: Serum leptin was positively associated with HbA1c in week 18, 22 and 30 (r=0.38, 0.41, and 0.54, respectively, p<0.05, adjusted for body weight). Moreover, serum leptin correlated positively with maternal body weight and BMI (0.4525 kg/m2), the changes during pregnancy and the level of serum leptin were significantly greater compared to lean women (p<0.05). The women with low ambulatory blood pressure (lower tertile, mean arterial blood pressure <83.4 mmHg) showed the lowest level of serum leptin throughout pregnancy and it changed significantly differently from the women with higher blood pressure (p<0.05). CONCLUSION: Changes in serum leptin levels of pregnant women with type 1 diabetes mellitus were associated with parallel changes in maternal body weight and glycemic control. Women with low blood pressure had the lowest serum leptin levels throughout pregnancy.     

血糖控制满意的妊娠期糖尿病孕妇血清性激素结合球蛋白水平与妊娠结局的关系

目的 探讨血糖控制满意的妊娠期糖尿病(GDM)孕妇血清性激素结合球蛋白(SHBG)水平与妊娠结局的关系.方法 选择2005年3月至2010年3月在中国医科大学附属盛京医院产科门诊确诊的妊娠24～28周GDM孕妇251例,其中经单纯饮食控制(169例)或加用胰岛素治疗(47例)后血糖控制满意的216例为血糖控制满意组;经单纯饮食控制或加用胰岛素治疗后血糖控制不满意的35例为血糖控制不满意组.选取同期妊娠24～28周的192例健康孕妇为健康对照组.分别于妊娠24～28周和妊娠＞36周两次测定孕妇血清SHBG水平和稳态模型的胰岛素抵抗(HOMA-IR)指数.依据美国糖尿病资料小组的GDM诊断标准采用"两步法"诊断GDM.记录并观察3组孕妇的妊娠结局.测定孕妇空腹血糖(FPG)和空腹胰岛素(FINS)水平.结果 (1)妊娠结局比较:血糖控制满意组孕妇的妊娠期高血压疾病(10.6%,23/216)、早产(8.3%,18/216)、大于胎龄儿(8.8%,19/216)、新生儿窒息(3.7%,8/216)和新生儿低血糖(2.3%,5/216)的发生率明显低于血糖控制不满意组[分别为42.9%(15/35)、34.3%(12/35)、31.4%(11/35)、22.9%(8/35)和11.4%(4/35)],两组分别比较,差异均有统计学意义(P＜0.05或P＜0.01);而两组孕妇羊水过多、产褥感染、产后出血和新生儿高胆红素血症的发生率比较,差异均无统计学意义(P＞0.05).血糖控制满意组孕妇早产、产褥感染(3.2%,7/216)、产后出血(5.1%,11/216)、新生儿窒息(3.7%,8/216)和新生儿低血糖(2.3%,5/216)的发生率,与健康对照组[分别为7.3%(14/192)、2.1%(4/192)、4.2%(8/192)、2.1%(4/192)和1.6%(3/192)]比较,差异均无统计学意义(P＞0.05).(2)妊娠24～28周与妊娠＞36周孕妇血清SHBG等项指标检测结果比较:血糖控制满意组孕妇血清SHBG水平[分别为(384±88)及(457±48)nmo]/L]均明显高于血糖控制不满意组[分别为(313±45)及(401±73)nmol/L];血糖控制满意组孕妇HOMA-IR指数(分别为5.3±1.1及5.5±1.1)均明显低于血糖控制不满意组(分别为7.0±1.3及7.6±1.7),两组分别比较,差异均有统计学意义(P＜0.01);血糖控制满意组孕妇血清SHBG水平均明显低于健康对照组[分别为(492±95)及(565±40)nmol/L];而HOMA-IR指数均明显高于健康对照组(分别为3.6±0.6及3.9±0.5),两组分别比较,差异均有统计学意义(P＜0.01);血糖控制满意组孕妇FPG水平[分别为(5.84±0.28)及(5.16±0.13)mmol/L]明显低于血糖控制不满意组[分别为(6.13±0.16)及(5.68±1.14)mmol/L],两组分别比较,差异均有统计学意义(P＜0.01);血糖控制满意组孕妇FINS水平[分别为(20.4±2.1)及(24.1±4.2)mmol/L]明显低于血糖控制不满意组[分别为(24.7±4.5)及(29.9±2.7)mmol/L],两组分别比较,差异均有统计学意义(P＜0.01).(3)相关性分析:妊娠24～28周时,3组孕妇(共443例)血清SHBG水平与HOMA-IR指数呈负相关(r=-0.952,P＜0.01);其中血糖控制满意组216例孕妇血清SHBG水平与HOMA-IR指数也呈负相关(r=-0.903,P＜0.01).结论 血糖控制满意的GDM孕妇并不能完全改善妊娠结局,GDM孕妇血清SHBG水平降低和高IR对其妊娠结局有一定影响.

Abstract：

Objective To explore the relationship between sex hormone-binding globulin (SHBG) of gestational diabetes mellitus ( GDM ) pregnant women with well-controlled glucose and pregnancy outcomes. Methods Two hundred and fifty-one GDM pregnant women of 24 - 28 weeks in Shengjing Hospital of China Medical University were recruited from Mar. 2005 to Mar. 2010. Two hundred and sixteen cases of GDM with well-controlled glucose were defined as glycemic satisfied group, and they were treated by diet therapy ( 169 cases) or insulin therapy (47 cases) . Thirty-five cases with unsatisfied glucose were defined as glycemic unsatisfied group. One hundred and ninety-two healthy pregnant women of 24 - 28 weeks were defined as healthy control group. Serum SHBG and homeostasis model analysis of insulin resistance ( HOMA-IR) at 24 - 28 weeks and above 36 weeks were measured. GDM was diagnosed by " two-step" method according to the National Diabetes Data Group ( NDDG) criteria. The pregnancy outcomes and complications of the three groups were recorded. Results ( 1 ) Comparison of pregnancy outcomes and complications: glycemic satisfied group was less likely to develop hypertensive disorders in pregnancy ( 10. 6% ) , premature birth(8. 3% ) ,large for gestational age ( LGA) (8. 8% ) , neonatal asphyxia(3. 7% ) and neonatal hypoglycemia ( 2. 3% ) compared to glycemic unsatisfied group ( 42. 9% , 34. 3% , 31. 4% , 22. 9% and 11. 4% ,respectively). And the difference was statistically significant (P ＜0. 05 or P ＜0. 01). There was no significant difference for incidence of polyhydramnios, pueperal infection, postpartum hemorrhage, neonatal hyperbilirubinemia between the two groups ( P＞ 0. 05 ) . When compared to healthy control group(7. 3% ,2. 1% ,4. 2% ,2. 1% and 1. 6% ) ,no significant difference was found for incidence of premature birth( 8. 3% ) , pueperal infection ( 3. 2% ) , postpartum hemorrhage (5. 1% ) , neonatal asphyxia (3. 7% )and neonatal hypoglycemia(2. 3% ,P ＞0. 05). (2) Comparison of results of 24 - 28 weeks and above 36 weeks: serum SHBG of glycemic satisfied group [( 384 ± 88 ) , (457 ± 48 ) nmol/L]was significantly higher than that of glycemic unsatisfied group[(313 ±45) ,(401 ±73) nmol/L];HOMA-IR of glycemic satisfied group (5. 3 ±1.1,5.5 ±1.1) was significantly lower than that of glycemic unsatisfied group (7. 0 ± 1. 3 ,7. 6 ± 1. 7 ; P ＜ 0. 01). Serum SHBG of glycemic satisfied group was significantly lower than that of healthy control group [( 492 ± 95 ) , (565 ± 40 ) nmol/L]; and HOMA-IR of glycemic satisfied group(5. 3 ± 1. 1,5. 5 ± 1. 1) was significantly higher than that of healthy control group (3. 6 ±0. 6,3. 9 ± 0. 5 ;P ＜ 0. 01 ) . FPG of glycemic satisfied group [( 5. 84 ± 0. 28 ) , ( 5. 16 ± 0. 13 ) mmol/L]was significantly lower than that of glycemic unsatisfied group [(6. 13 ± 0. 16 ) , ( 5. 68 ± 1. 14) mmol/L; P ＜ 0. 01]. FINS of glycemic satisfied group [( 20. 4 ± 2. 1 ) , ( 24. 1 ± 4. 2 ) mmol/L]was significantly lower than that of glycemic unsatisfied group [(24. 7 ± 4. 5 ) , ( 29. 9 ± 2. 7 ) mmol/L; P ＜ 0. 01]. ( 3 ) Correlation analysis. Between 24 - 28 weeks, SHBG was negatively correlated with HOMA-IR in the three groups ( r = -0. 952, P ＜0. 01) ; and SHBG was negatively correlated with HOMA-IR in glycemic satisfied group ( r = -0. 903, P ＜0. 01). Conclusions Well-controlled glucose can not completely improve maternal and fetal outcomes of GDM pregnant women. High insulin resistance and low serum SHBG can influence pregnancy outcomes.     

Dietary advices on carbohydrate intake for pregnant women with type 1 diabetes

The impact of the quality and quantity of carbohydrate intake on glycaemic control and pregnancy outcome was evaluated with focus on pregnant women with type 1 diabetes. For women with type 1 diabetes, a gestational weight gain within the lower range of the guidelines of the Institute of Medicine (IOM) is generally recommended. A low-glycaemic index diet is considered safe, and has shown, positive effects on the glycaemic control and pregnancy outcomes for both healthy women, those with type 2 diabetic and gestational diabetes (GDM). In general, carbohydrate counting does improve glycaemic control in type 1 diabetes. A moderately low carbohydrate diet with a carbohydrate content of 40% of the calories results in better glycaemic control and comparable obstetric outcomes in type 2 diabetes and GDM when compared to a diet with a higher carbohydrate content, and is regarded safe in diabetic pregnancy. In type 1 diabetes pregnancy, a moderately low carbohydrate diet with 40% carbohydrates has been suggested; however, a minimum intake of 175?g carbohydrate daily is recommended. Despite limited evidence the combination of a low-glycaemic index diet with a moderately low carbohydrate intake, using carbohydrate counting can be recommended for pregnant women with type 1 diabetes.     

Macrophage migration-inhibitory factor is elevated in pregnant women with gestational diabetes mellitus

Objective: In reports, abnormal macrophage migration-inhibitory factor (MIF) production has been associated with several diseases. Furthermore, despite scarce data, increasing evidence suggest that MIF plays a central role in glucose homeostasis and in the development of type 1 and type 2 diabetes. However, serum MIF levels in gestational diabetes mellitus (GDM) have not yet been investigated. To address this question, we performed a prospective study between a group of pregnant women with GDM and healthy pregnant controls. Materials and methods: GDM group consisted of 43 pregnant women, whereas the control group consisted of 40 healthy pregnant women. In the morning after an overnight fast, venous blood was sampled for the measurement of serum concentrations of insulin and MIF. Serum was separated by centrifugation and immediately stored at ?80°C until the assay. Results: There was no significant difference between the groups for maternal characteristics. Women with GDM had significantly higher levels of serum insulin (14.37?±?9.92 µU/ml vs. 8.78?±?4.35 µU/ml; p?=?0.001) and serum MIF concentrations (11.31?±?4.92?ng/ml vs. 5.31?±?4.07?ng/ml; p?<?0.001) when compared with healthy pregnant control group. Conclusion: Our data demonstrated that serum levels of MIF are significantly elevated in patients with GDM. Our findings indicate that MIF might have a role in GDM; however, there is a need for further investigation.     

Endothelial function in myometrial resistance arteries of normal pregnant women perfused with syncytiotrophoblast microvillous membranes

Objective To investigate the effects of syncytiotrophoblast microvillous membranes (STBM) in concentrations, found in vivo in women with pre-eclampsia, on endothelial function in isolated resistance arteries.
Setting Department of Obstetrics and Gynaecology, Huddinge University Hospital, Stockholm.
Sample Twenty-nine myometrial resistance arteries isolated from biopsies of healthy term pregnant women, obtained during caesarean section.
Methods The myometrial arteries were mounted in a pressure arteriograph and perfused intraluminally for three hours with STBM (20 to 2000ng/mL) or with erythrocyte membranes or physiological salt solution as controls, all substituted with 0.5% bovine serum albumin. Bradykinin concentration-response curves were performed before and after perfusion.
Main outcome measures The bradykinin concentrationresponse curves were fitted to the Hill equation and maximal dilation and the  pEC₅₀  values were determined from these fits. Differences within groups were analysed with a paired  Student's t test  . Electron microscopic evaluation of the endothelium was performed.
Results Neither STBM nor erythrocyte membrane perfusion affected maximal dilation or the  pEC₅₀  values of the bradykinin concentration-response curves at any concentration. Examination by electron microscopy showed no obvious damage to the endothelium after perfusion with STBM or erythrocyte membranes.
Conclusion Perfusion with STBM in concentrations up to 100 times those reported in pre-eclampsia has no significant effect on bradykinin-mediated dilation in isolated myometrial arteries.     

Sudden fetal death in women with well-controlled, intensively monitored gestational diabetes.

An intensive antepartum monitoring system for women with gestational diabetes mellitus was evaluated over a 5-year period. Early diagnosis and liberal treatment with insulin was concomitantly followed with non-stress testing: weekly from 28 to 34 weeks' gestation and semi-weekly thereafter. Despite maternal euglycemia and satisfactory antepartum assessment, three fetal deaths occurred within 72 hours of reassuring fetal monitoring. Additionally, 24 (7%) fetuses were delivered on the basis of a low biophysical profile score (less than 6) at term. The stillbirth rate for women with gestational diabetes was 7.7/1000, whereas the stillbirth rate for nondiabetic low-risk patients was 4.8/1000. Women with gestational diabetes continue to be in a high-risk category for antepartum fetal death, requiring intensive monitoring with consideration for timely delivery.     

Obstetric interventions for women with type 1 or type 2 diabetes

Objective

To determine whether differences exist in the rates of obstetric intervention between women with type 1 diabetes and those with type 2 diabetes, and whether there has been any change in cesarean rates over time, paralleling that seen in the general obstetric population.

Methods

Data were examined from a prospectively collected series on the outcomes of 1030 deliveries (382 by women with type 1 diabetes, 648 by women with type 2 diabetes) from 1988 to 2008.

Results

There was a secular trend to increasing maternal age (type 1, P < 0.003; type 2, P < 0.03). Intervention rates (induction of labor or elective cesarean) did not differ between type 1 (88%) and type 2 (85%) diabetes. The overall cesarean rate was 52%–55% with no secular trend. Poorer glycemic control in early pregnancy and primiparity were associated with primary cesarean in both groups. In women with type 1 diabetes, greater maternal obesity and retinopathy were also associated with primary cesarean.

Conclusion

Intervention rates are high in pregnancies among women with type 1 diabetes and those with type 2 diabetes but they have not changed significantly. Secular trends toward increasing maternal age and obesity suggest that intervention rates are unlikely to decrease in the near future.     

Sexual function in women with type 1 diabetes matched with a control group: depressive and psychosocial aspects

IntroductionSexual dysfunction in women with diabetes, despite its important consequences to their quality of life, has been investigated only recently with conflicting results about its prevalence and association with complications and psychological factors.AimsTo assess the prevalence of the alteration of sexual function and the influence of metabolic control and psychological factors on female sexuality.MethodsSeventy-seven adult Italian women with type 1 diabetes, matched with a control group (n = 77), completed questionnaires evaluating sexual function (Female Sexual Function Index, FSFI), depressive symptoms (Self-Rating Depression Scale, SRDS), social and family support (Multidimensional Scale of Perceived Social Support), and diabetes-related quality of life (Diabetes Quality of Life). Clinical and metabolic data were collected.Main Outcome MeasuresPrevalence and magnitude of sexual dysfunction in terms of alteration of sexual functioning as measured by the FSFI scores.ResultsThe prevalence of sexual dysfunction was similar in diabetes and control groups (33.8% vs. 39.0%, not significant), except for higher SRDS scores in the diabetes group (47.39 ± 11.96 vs. 43.82 ± 10.66; P = 0.047). Diabetic patients with an alteration of sexual function showed a significantly higher SRDS score (53.58 ± 14.11 vs. 44.24± 9.38, P = 0.004). Depression symptoms and good glycemic control (A1C < 7.0%) were predictors of alteration of sexual function only in diabetic patients (odds ratio [OR] = 1.082; 95% confidence interval [CI]: 1.028–1.140; OR = 5.085; 95% CI: 1.087–23.789), since we have not found any significant predictor of sexual dysfunction in the control group.ConclusionsThe prevalence of sexual dysfunction in our type 1 diabetes patients' sample is similar to those reported in other studies. Diabetic patients are similar to healthy people except for higher depression scores. Further studies are necessary to understand whether the correlation between an alteration of sexual function and good glycemic control may be related to the role of control as a mental attitude. Tagliabue M, Gottero C, Zuffranieri M, Negro M, Carletto S, Picci RL, Tomelini M, Bertaina S, Pucci E, Trento M, and Ostacoli L. Sexual function in women with type 1 diabetes matched with a control group: Depressive and psychosocial aspects.     

Clinical outcomes of pregnancy in women with type 1 diabetes(1)

OBJECTIVE:To evaluate predictors of neonatal hypoglycemia and macrosomia in 107 consecutive pregnancies in type 1 diabetic women. METHODS:We conducted a case record analysis of singleton type 1 diabetic pregnancies between January 1994 and January 1999 following institution of standardized management. RESULTS:The duration of diabetes in the women was 12.9 +/- 6.8 years, and 44 were primigravidas. The mean HbA1c throughout pregnancy was 7.2 +/- 0.8%. There was no relationship between neonatal blood glucose (checked before the second feed) and HbA1c at any point in pregnancy or mean pregnancy HbA1c (R = 0.20, P >.1). However, there was a negative correlation between neonatal blood glucose and maternal blood glucose during labor (R = -0.33, P <.001). When maternal blood glucose during labor was greater than 8 mM (144 mg/dL), neonatal blood glucose was usually less than 2.5 mM (mean 1.7 +/- 0.4 mM or 31 mg/dL). There was no relationship between mean HbA1c and birth weight (R = 0.02, P >.1) or between maximum insulin dose and birth weight (R = 0.09, P >.1). Fetal abdominal circumference measured by ultrasound at 34 weeks correlated strongly with birth weight (R = 0.72, P <.001). CONCLUSION:Neonatal hypoglycemia correlates with maternal hyperglycemia in labor, not with HbA1c during pregnancy. Macrosomia does not correlate with HbA1c during pregnancy.     

Activity of alpha-amylase in serum and urine of pregnant women with diabetes mellitus type I]

The investigations covered 33 women in the III trimester of pregnancy with diagnosed, insulin-dependent diabetes mellitus, and 108 healthy women in the control group. The alpha-amylase activity was measured in the blood-serum and urine samples using the Caravay technique. An increased activity was demonstrated in the blood-serum samples in the examined group. The values were not related to the levels of glycemia. The urinary alpha-amylase activity was similar to that in the control patients. No coincidence between the activity and glycemia or acetone levels could be demonstrated.     

Cyproterone acetate improves beta-cell function in postmenopausal women with diabetes mellitus type 2

Menopause is associated with two main risk factors for the development of type 2 diabetes mellitus--impaired beta-cell insulin secretion and insulin resistance. Physiologically estrogens improve carbohydrate metabolism, but this is not the case with different progestogens. The aim of the present study was to evaluate the effect of Cyproterone acetate (a progestogen with antiandrogenic activity) on insulin secretion, peripheral insulin sensitivity, lipid parameters and parameters of oxidative stress. Seven type 2 diabetic females, of mean age 55.4 +/- 4.7 years and mean BMI 30.8 +/- 9.39 kg/m2, in menopause for average 5 years, in good borderline glycaemic control (mean HbAic 7.8%), with dyslipidaemia, normal parameters of calcium and phosphate metabolism and with osteopenia (T-score < 88%) were enrolled in the study. They were treated with Estradiol valerate + Cyproterone acetate (Climen, Schering) for three months. Phases of insulin secretion--first phase (FPIS), second phase (SPIS) and AUC for FPIS and SPIS were assessed during IVGTT. Insulin sensitivity was determined with the manual method of euglycaemic hyperinsulinaemic clamp technique. The postmenopausal diabetic women in the present study were with overweight and obesity; they did not increase their body weight during HRT and even decreased it by mean 0.7%. Insulin secretion improved after Climen--FPIS increased by 16% and SPIS by 44%. Insulin sensitivity increased by 15%; triglycerides decreased by 16% and HDL-cholesterol increased by 27%. Total antioxidant capacity of the serum (TAOK) increased by 7%. The favourable effect on the pathophysiological mechanisms improved metabolic control--HbAic was reduced by mean 3% after 3 months. In conclusion, our results suggest that HRT with the progestogen Cyproterone acetate (Climen) should be preferred in postmenopausal type 2 diabetic females with predominant beta-cell insulin secretion defect.     

The influence of prenatal glucocorticoids on glycemic control among pregnant women with type I diabetes

The purpose of this study was to determine the impact of glucocorticoids treatment, administered for a severe risk of premature delivery. The study material consisted of 30 diabetic mothers treated with intensive insulin therapy. The effects of steroid treatment on glucose level two days prior, one day prior, during 1-, or 2-, or 3-days therapy and the first 2 days following treatment were determined. No case of ketoacidosis was reported.