妊娠合并糖尿病酮症酸中毒的识别和处理

妊娠合并糖尿病酮症酸中毒是产科严重的合并症,如未能及时诊断及处理,会造成母儿严重的不良结局.本文就妊娠合并DKA的临床识别及处理进行讨论.     

Maternal overweight and pregnancy outcome in women with Type-1 diabetes mellitus and different degrees of nephropathy

Objective.?We aimed to assess the parameters associated with complicated pregnancy in women with Type 1 diabetes mellitus (DM) and nephropathy.

Study design.?A cohort study of 46 consecutive women diagnosed with Type 1 DM with nephropathy prior to pregnancy was included during the years 2000–2007. Complicated pregnancy was defined as one or more of the following: first trimester abortion, superimposed pre-eclampsia, pre-term delivery?<34 weeks, small and large for gestational age neonate, macrosomia, admission to the neonatal intensive care unit and foetal loss (after 22 weeks' gestation).

Results.?Overall, 31/46 (67%) had at least one pregnancy complication. Body mass index (BMI) was the only parameter with a significant difference between the groups, being higher in the women with complicated pregnancy vs. uncomplicated pregnancy (27?±?9 vs. 24?±?3, p?=?0.027). On Multiple logistic regression model in which composite outcome (pregnancy complication) as the dependent variable, pre-pregnancy BMI was the only statistically significant parameter with a difference between the groups (p?=?0.044). No statistical difference was found between the groups in the rate of pre-pregnancy counselling (60% vs. 67%), glycaemic control prior to pregnancy (Hba1c 7.5 vs. 7.1%), the prevalence of patients achieving desired level of glycaemic control (44% vs. 42%), weight gain during pregnancy (12.4 vs. 10.6?kg), duration of DM (18.0 vs. 19.7 years) and proportion of patients treated with angiotensin converting enzyme inhibitors prior to pregnancy (26 vs. 33%).

Conclusion.?Overweight is associated with poor pregnancy outcome in patients with Type-1 DM and different degrees of nephropathy.     

妊娠合并糖尿病酮症酸中毒12例临床分析

目的:探讨妊娠合并糖尿病酮症酸中毒(DKA)的临床特征。方法:回顾性分析本院收治的资料完整的妊娠合并DKA 12例患者的临床特征和母儿结局。结果:本组妊娠合并DKA发病率0.36‰;发生在孕早期1例(8.3%)、孕中期2例(16.7%)、孕晚期9例(75.0%);孕前糖尿病(PGDM)8例(66.7%),妊娠期糖尿病(GDM)4例(33.3%)。12例均为单胎自然妊娠、均未进行孕前咨询及正规产检,有不良孕产史4例,孕前超重4例,既往血糖升高史1例,糖尿病家族史1例。12例均未规范产检且胰岛素用量不足;感染5例(41.7%),重度子痫前期3例(25.0%),地塞米松诱发2例(16.6%),先兆临产应激2例(16.6%),饮食不当1例(8.3%)。实验室检查,p H值7.050~7.319,BE-11.6~-28.8,平均血糖20.91±6.13 mmol/L,平均血酮体3.06±1.44 mmol/L,平均糖化血红蛋白(Hb A1c)为(9.04±2.09)%,10例患者尿糖阳性,12例患者尿酮体均为阳性,且均存在不同程度的电解质紊乱。12例患者均在4~8小时内成功酮体转阴,血糖控制达标。入院前就发生死胎者3例,难免流产1例;入院后仅8例继续妊娠,其中4例因妊娠合并症在DKA纠正后的1~3天终止妊娠,4例妊娠足月分娩,8例新生儿均存活。结论:妊娠合并DKA的发病率随孕周的增加而增加,PGDM比GDM者更易发生;患者存在不同程度的内环境紊乱及胰岛素使用不规范和感染。高危妇女应规范筛查并积极诊治糖尿病,早期识别并规范处置DKA,可获得良好的母儿预后。     

Use of angiotensin-converting enzyme inhibitors in patients with diabetic nephropathy

Diabetic nephropathy is the most common cause of end-stage renal failure in the Western world. It accounts for 15–25% of all renal failure in patients requiring chronic dialysis. About 20% of patients with insulin-dependent diabetes and less than 15% of patients with non-insulin-dependent diabetes develop clinically significant nephropathy. The prevalence of diabetic nephropathy in pregnant patients with insulin-dependent diabetes is estimated to be 6%. Angiotensin converting enzyme (ACE) inhibitors are the drug of choice in treating women with diabetic nephropathy. In addition, many of these drugs may be started before conception. Unfortunately, these agents might be fetotoxic when taken during pregnancy. This article reviews the epidemiology and natural history of diabetic nephropathy, discusses the renoprotective effect of ACE inhibitors, reviews the effect of ACE inhibitors on fetomaternal outcome when used prior to and during pregnancy in women with diabetic nephropathy and discusses the new class of drugs, angiotensin II receptor antagonists, in the management of diabetics who have or are prone to developing diabetic nephropathy.     

糖尿病家族青春期多囊卵巢综合征胰岛素抵抗的临床特征和治疗

目的:探讨糖尿病(DM)家族青春期多囊卵巢综合征(PCOS)胰岛素抵抗(IR)的程度及应用二甲双胍治疗的效果。方法:选择父亲或母亲被确诊患DM的7例青春期PCOS患者为实验组,以无DM家族史的28例青春期PCOS患者为对照组。测体重指数(BM I)、基础体温(BBT),抽血测FSH、LH、PRL、T、E2、P,行75g葡萄糖耐量试验(OGTT)和胰岛素释放试验(IRT)。计算空腹血糖胰岛素比率(FGIR)、糖负荷120m in血糖胰岛素比率(G120/I120)及稳态模型的胰岛素抵抗指数(HOMA-IR)。确诊IR患者进行包括二甲双胍在内的综合治疗,每3月重复检测1次上述指标。结果:实验组7例均超重(BM I≥25),其比率明显高于对照组(7/7vs12/28,P<0.01);实验组IR患病率亦明显高于对照组(7/7vs 9/21,P<0.01),且IR程度明显高于对照组IR患者(HOMA-IR为14.35vs 6.02,P<0.01)。两组接受二甲双胍综合治疗的IR患者治疗6月后空腹胰岛素(I0)比治疗前明显降低(32.47vs 40.36,P<0.05),胰岛素敏感性(IS)明显提高(FGIR为3.42 vs2.99,P<0.05),T降低,并有3例卵巢恢复排卵。结论:DM家族青春期PCOS患者可能存在较重IR,坚持二甲双胍综合治疗可减轻IR程度并恢复卵巢排卵功能。     

Comparison of placental findings in type 1 and type 2 diabetic pregnancies

IntroductionThe aim of this study is to compare placental pathology and related clinical parameters between gravidas with type 1 and type 2 pregestational diabetes.MethodsThis is a retrospective cohort study of women with singleton gestations and pregestational diabetes who delivered at Women and Infants Hospital from 2003 to 2011. Pathology reports, maternal and neonatal outcomes were extracted and compared between the two groups.ResultsIn our cohort, 293 pregnancies were studied, including 117 with type 1 diabetes and 176 with type 2 diabetes. Women with type 1 diabetes had worse glycemic control during pregnancy, as characterized by higher HbA1c values and average fasting and postprandial blood sugars. More infants from the type 1 group were admitted to Neonatal ICU. Pregestational diabetes led to small for gestational age (SGA) placentas in nearly 20% pregnancies and large for gestational age (LGA) placentas in 30% of cases. Both groups shared similar incidences of preeclampsia and significant placental pathology related to uteroplacental (maternal) and fetal circulatory disorders; however, maternal decidual vasculopathy and placentas with insufficiency (fetal-to-placental weight ratio < 10th %tile) were more commonly found in placentas from women with type 2 diabetes.DiscussionBoth types of pregestational diabetes have significant impact on placental growth and development. The comparison between the two groups suggests different pathogenetic mechanisms and may be helpful for better management of diabetic pregnancy.     

Prediction of proteinuria and microalbuminuria in diabetic pregnancies with a random single void

Objective.?To determine whether a single urine specimen could effectively replace the 24 hour (24-h) urine collection in screening for microalbuminuria and proteinuria in pregnant women with pregestational diabetes.

Materials and Methods.?A total of 42 pregnant women with pregestational diabetes mellitus were involved in the eventual analysis. Demographic and clinical variables were collected and analyzed. Urinary Protein (P) to Creatinine (Cr) ratio and microalbumin (MA) to Cr ratios were measured for the spot sample, and the total P, total MA, and serum Cr were measured for the 24-h urine sample. Analysis was done using linear regression and the Pearson correlation coefficient (r).

Results.?Mean maternal age was 30.8 years, and the mean gestational age at collection was 19.8 weeks. A strong correlation exists between the spot MA to Cr value and 24-h MA, with an r?=?0.81 (P?<?0.0001). The association between the spot P to Cr ratio and 24-h urinary P was not as strong, r?=?0.58 (P?<?0.0001).

Conclusions.?A strong association between spot MA to Cr ratio and 24-h urinary microalbuminuria may suggest a predictive role for random urine assessment of MA in pregnant pregestational diabetic patients. However, based on our data, the spot P to Cr ratio may be inadequate for assessing proteinuria in pregestational diabetic pregnancies.     

Experience with real time continuous glucose monitoring in stabilising fluctuating glycaemia during intensive care of the preterm infant of a diabetic mother

Abstract

Objective: The newborns of diabetic mothers suffer from perinatal complications more frequently than the newborns of healthy women.

Methods: We used for 7 days a real time continuous glucose monitoring system (RT-CGMS) to monitor glucose homeostasis and manage glucose administration in a premature newborn of a diabetic mother.

Results: The boy was born at 35?+?5 gestational weeks with typical signs of diabetic fetopathy. RT-CGMS revealed 2 late hypoglycaemia episodes on the 2nd and 4th days. The sensor readings correlated well with glycaemia measured in the laboratory (r?=?0.908, p?=?0.005). To support conclusions of this case report, we attached the data of five other preterm newborns of diabetic mothers who were later successfully treated according to the RT-CGMS data as well.

Conclusions: This approach allows timely response to glycaemia instability and is applicable even in preterm infants.     

Estriol reaction test for evaluation of the fetoplacental function: preliminary data on normal and diabetic pregnancies in the third trimester

A single i.v. injection of 4 mg dexamethasone was given to 6 diabetic gravidas and 4 controls in the 36th–38th gestational week. Unconjugated estriol (E₃) was measured by radioimmunoassay in maternal serum before dexamethasone injection and 4, 8, 24, 28 and 32 h thereafter. During such an estriol reaction test (E₃RT) the following were noted: (1) suppression of the fetal adrenals causes a drop in maternal E₃ on day 1 of the test in both groups; (2) on day 2, E₃ in the controls is rising faster than in the diabetics; (3) rising E₃ levels in the controls show a distinctive course, which is significantly different from that in the diabetics (P < 0.05) and which reveals an ‘overshoot’ of E₃; (4) this ‘overshoot’ on day 2 finds confirmation by polynomial curve-fitting; and (5) analysis of E₃ response in maternal serum might be helpful in differentiating between normal fetoplacental function and fetoplacental impairment in pregnancies complicated by diabetes mellitus. However, the clinical application of the E₃RT awaits further data collected from a larger number of patients.     

青春早期SD雌性大鼠在阿霉素肾病模型过程中生长发育的变化

目的观察青春早期SD雌性大鼠在阿霉素肾病模型过程中生长发育的变化。方法选取4周龄SPF级雌性SD大鼠10只,随机分为观察组和对照组各5只。观察组大鼠经尾静脉注射阿霉素6.5mg/kg制备肾病模型,对照组大鼠经尾静脉注射等量生理盐水。观察阿霉素注射后1、2、3、4周SD大鼠体质量、子宫湿重、头尾长、胫骨长度变化及测定24h尿蛋白;透射电镜下观察足细胞超微结构变化;放射免疫法分析血清雌二醇(E_2)、促黄体生成素(LH)、促卵泡生成素(FSH)、胰岛素样生长因子1(IGF-1)、胰岛素样生长因子结合蛋白3(IGFBP-3)的变化。结果阿霉素注射后4周青春早期SD雌性大鼠尿蛋白显著高于对照组,差异有统计学意义(P0.05)。青春期雌性SD大鼠在阿霉素注射后足细胞足突融合逐渐加剧,在阿霉素注射后4周雌性SD大鼠肾小球足细胞足突出现广泛融合。观察组体质量在阿霉素注射后2、3、4周减轻逐渐加剧,与对照组比较差异有统计学意义(P0.05)。观察组头尾长在阿霉素注射后4周较对照组明显减少,差异有统计学意义(P0.05)。观察组胫骨长度和子宫湿重在阿霉素注射后2、3、4周后与对照组比较无明显减少,差异无统计学意义(P0.05)。观察组血清LH、FSH、E_2、IGF-1和IGFBP-3在阿霉素注射后2、3、4周与对照组比较无明显改变,差异无统计学意义(P0.05)。结论青春早期雌性SD大鼠在阿霉素肾病模型过程中未出现明显的生长发育迟滞,血清生长相关激素和性激素分泌未出现明显降低。     

High Uric Acid Level During the First 20 Weeks of Pregnancy is Associated with Higher Risk for Gestational Diabetes Mellitus and Mild Preeclampsia

Objective. To examine the association between uric acid (UA) level during the first 20 weeks of pregnancy and the development of gestational diabetes mellitus (GDM) and preeclampsia in the second half of pregnancy. Methods. The study population included registered births (n = 5507) between 2001 and 2007 in a tertiary medical center. The UA levels during the first 20 weeks of pregnancy were sorted by UA ≤ 2.4 mEq/L; UA = 2.5–4.0 mEq/L, UA = 4.1–5.5 mEq/L, and UA > 5.5 mEq/L. The linear-by-linear chi-square test and ROC curves were used to determine the association between UA level during the first 20 weeks and pregnancy complications. Multivariate analyses were performed to demonstrate whether UA level is an independent factor for the prevalence of preeclampsia and GDM. Results. Significant linear association was documented between UA level in the first 20 weeks and the prevalence of GDM and mild preeclampsia. The lowest and the highest prevalence of GDM were found in the UA ≤ 2.4 mEq/L group (6.3%) and in the UA > 5.5 mEq/L group (10.5%) (p < 0.001), respectively. Mild preeclampsia was diagnosed in 2.1% of the patients from the UA ≤ 2.4 mEq/L group, 3.3% from the UA = 2.5–4.0 mEq/L group, 5.3% from the UA = 4.1–5.5 mEq/L group, and 4.5% from the UA > 5.5 mEq/L group (p < 0.001). Three multiple logistic regression models controlling for maternal age showed that UA level is an independent risk factor for both GDM and mild preeclampsia. Conclusions. UA levels in the highest quartile of the normal range during the first 20 weeks of pregnancy are associated with higher risk for the development of GDM and mild preeclampsia.     

The risk of preeclampsia beyond the first pregnancy among women with type 1 diabetes parity and preeclampsia in type 1 diabetes

AimTo estimate the incidence of preeclampsia (PE) among nulliparous and multiparous patients with type 1 diabetes and to study predictors of PE.MethodsWe prospectively collected data on all pregnancies of patients with pregestational type 1 diabetes, followed at our Prenatal Medicine Unit between 1993 and 2008. Medical records were prospectively reviewed by two obstetricians for maternal demographics, pregnancy data, maternal and fetal outcomes. Data were analyzed according to the development of PE and parity.ResultsWe identified and collected data on 291 eligible pregnancies (195 among nulliparae and 96 among multiparae). The incidence of PE was 9.2% (95% CI: 5.6–14.2) among nulliparae and 9.4% (95% CI: 4.4–17.0) among multiparae. Patients who developed PE had higher HbA1c during pregnancy compared to patients who did not (p = 0.026 among nulliparae and p = 0.032 among multiparae). Chronic hypertension [OR 17.12 (3.22, 91.00)], microalbuminuria at the beginning of the pregnancy [OR 3.77 (1.22, 11.61)], weight gain during pregnancy [OR 1.13 (1.04, 1.23)] and HbA1c in the first trimester [2.81 (1.12, 7.05)], but not parity, were significant predictors of PE.ConclusionsAmong patients with type 1 diabetes the incidence of PE was similar among nulliparae and multiparae, unlikely in the general population where PE is a disease of the first pregnancy. An increased risk of PE should be assumed for both nulliparous and multiparous women with pregestational diabetes.     

妊娠期糖尿病和2型糖尿病患者HLA-II类基因的比较研究

目的:从免疫遗传学角度比较妊娠期糖尿病和2型糖尿病的异同。方法:采用顺序特异引物聚合酶链反应技术检测48例妊娠期糖尿病和48例2型糖尿病患者的部分HLA-II等位基因频率,并与48名正常孕妇比较。结果:两患者组的HLA-DRB1*0301等位基因频率为18.8%,35.4%,均明显高于对照组,差异有显著性(P=0.025,P=0.066);两患者组的HLA-DQA1*0301等位基因频率分别为64.6%,75.0%,均明显高于对照组,差异有显著性(P=0.024,P=0.001);两患者组之间所测各等位基因频率比较,差异无显著性。结论:妊娠期糖尿病及2型糖尿病均与HLA-DRB1*0301、DQA1*0301相关,从所测部分HLA-II类等位基因角度分析,二者的发病机理可能有共同之处。     

化学药物对卵巢恶性肿瘤患者血糖代谢的影响

目的 探讨化学药物对卵巢恶性肿瘤患者血糖代谢的影响。方法 收集1997年1月－2001年12月收治的卵巢恶性肿瘤患者375例化学药物治疗（化疗）前后的血糖检测报告及相关临床资料,并对其进行回顾性分析。结果 375例患者中,化疗前合并糖尿病9例,其余化疗前血糖水平正常。化疗后空腹血糖升高32例,占8.5%。32例中明确诊断为糖尿病14例,糖耐量低减9例,一过性血糖升高9例,分别占同期接受化疗的卵巢恶性肿瘤患者的3.7%、2.4%和2.4%。其中,接受以紫杉醇类药物为主的中患者208例,发生血糖异常23例,占同类化疗11.1%(23/208),占同期化疗6.1%（23／375）;接受以铂类药物为主的化序患者141例,发生血糖异常8例,占同类化疗5.7%(8/141),占同期化疗2.1%（8／375）;接受其他化疗方案患者26例,发生血糖异常1例,占同期化疗0.3%（1／375）。以紫杉醇类为主化疗与以铂类为主化疗引起的血糖异常的发生率相比较,差异有显著性（P＜0.05）。化疗诱发的血糖异常多数发生的化疗后1－3个疗程。结论 卵巢恶性肿瘤患者接受化疗后可能会出现血糖异常,甚至发生糖耐量低减或糖尿病,以紫杉醇为主的化疗方案治疗中这种情况更加常见,且多发生于治疗的第1－3个疗程,对此应予以重视。     

孕前糖尿病围孕期咨询和评估及降糖药应用

孕前糖尿病占所有妊娠合并糖尿病的5%~10%,妊娠前咨询内容包括了解血糖水平、评估慢性并发症及合并症以确定合适的妊娠时机。资料表明,相对比较安全的孕期口服降糖药是格列本脲和二甲双胍,目前仍推荐孕期使用胰岛素控制血糖。