Continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) of rapid-acting insulin analogues and detemir in type 1 diabetic (T1D) pregnant women

Objective: To compare glycemic control, maternal-neonatal outcomes and fetal fat body mass growth of type 1 diabetic pregnant women treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) with the long-acting insulin analogue detemir as basal insulin.

Methods: Retrospective study of 53 women, attending the Unit of Prenatal Medicine of Careggi University Hospital, Florence, from 2009 to 2012: 35 treated with CSII, 18 with MDI-detemir. Each woman performed daily blood glucose self-monitoring, had an individualized nutritional therapy, weekly prenatal visits and ultrasound scans (US) according to the Tuscan guidelines. US were also performed every two weeks from 28 to 38 weeks of gestation to assess fetal fat body mass growth. Student’s t-test and Chi-square test were performed to compare the groups’ results.

Results: No significant differences were observed in metabolic control, in any maternal and neonatal outcome nor fetal fat body mass growth for either group. The MDI group needed higher daily doses of insulin (MDI: 1.00?±?0.32 UI/kg versus CSII: 0.75?±?0.29 UI/kg, p?=?0.007) to reach results comparable to the CSII group.

Conclusions: MDI therapy with detemir is a safe and effective alternative, with a good benefit–cost ratio compared to insulin pumps.     

Continuous glucose monitoring and insulin pump therapy for diabetes in pregnancy

Continuous glucose monitoring (CGM) systems and continuous subcutaneous insulin infusion (CSII) systems, or insulin pumps, offer great promise for improved glycemic control during pregnancy. Combined, these two devices could potentially constitute an artificial pancreas, where real-time blood glucose readings are relayed to an insulin pump that uses a personalized algorithm to decide how much insulin is needed by the patient’s body. However, the promise of these two systems have not yet been proven individually or in combination in controlled clinical trials to improve pregnancy outcomes. Such trials are urgently needed before the widespread use of these devices in pregnancy can be justified.     

儿童1型糖尿病动态血糖监测的临床意义

目的应用动态血糖监测系统(CGMS)观察1型糖尿病患儿血糖控制情况，寻找评价和改善血糖控制的方法。 方法收集复旦大学附属儿科医院2003年10月至2004年6月内分泌科门诊随访的儿童1型糖尿病患者28例，男16例，女12例，年龄(131±45)岁，病程(55±34)年，其中21例采用每天多次胰岛素注射(MDI),另7例使用胰岛素泵连续胰岛素输注(CSII)治疗。动态监测血糖3d，同时指尖血糖监测≥4次/d。 结果(1)研究对象体重指数(BMI)为(194±30)kg/m2,糖化血红蛋白(HbA1c)为(84±16)%。CSII组HbA1c(82±10)%,MDI组HbA1c(85±18)%,差异有显著性意义(P<005);(2)CGMS发现22例77次餐后2h高血糖，CSII组4例(571%),每例出现1次，MDI组18例(857%),每例出现(41±25)次,差异显著(P<001)；(3)CGMS发现17例79次低血糖，持续时间(766±928)min,而指尖血糖监测仅发现19次低血糖;白天低血糖持续时间(415±391)min，夜间(1124±1171)min，夜间低血糖持续时间显著长于白天(P<001)。(4)HbA1c≤8%组餐后高血糖发生率低于HbA1c>8%组(P<005)，而低血糖的发生率显著升高(P<001)。 结论1型糖尿病患儿多数存在低血糖和餐后高血糖；动态血糖监测系统是发现血糖异常波动的有效工具。动态血糖监测对指导1型糖尿病治疗，调整胰岛素剂量，从而改善血糖控制有着重要的临床意义。     

Continuous subcutaneous insulin infusion vs intensive conventional insulin therapy in pregnant diabetic women: a systematic review and metaanalysis of randomized, controlled trials

The objective of the study was to study the effects of continuous subcutaneous insulin infusion (CSII) vs multiple-dose insulin (MDI) therapy on glycemic control and pregnancy outcome in diabetic women. Randomized, controlled trials comparing CSII vs MDI in pregnant diabetic women were included after an electronic database search. Studies were rated for quality independently by 2 reviewers in accordance with the Quality of Reporting of Metaanalyses statement. Summary weighted mean difference and odds ratio were estimated for insulin dose, birthweight, gestational age, mode of delivery, hypoglycemic/ketotic episodes, worsening retinopathy, neonatal hypoglycemia, and rates of intrauterine fetal death. Six randomized clinical trials met the inclusion criteria. Pregnancy outcomes and glycemic control were not significantly different among treatment groups. Higher number of ketoacidotic episodes and diabetic retinopathy found in the CSII group did not reach statistical significance. This systematic review does not show any advantage or disadvantage of using CSII over MDI in pregnant diabetic women. Large multicenter, randomized, controlled trials addressing the quality of life/cost effectiveness are required.     

Evaluation of serum ischemia-modified albumin levels in pregnant women with and without gestational diabetes mellitus

Objective. To investigate serum ischemia-modified albumin (IMA) levels in gestational diabetes mellitus and the effect of treatment with continuous subcutaneous insulin infusion on the biomarker. Methods. The gestational diabetes mellitus women in the second trimester were evaluated before and after the two kinds of treatments with continuous subcutaneous insulin infusion and medical nutrition therapy for 6 weeks. Maternal serum ischemia-modified albumin and metabolic parameters were measured at baseline and at the 6th week. Results.Serum ischemia-modified albumin levels and metabolic parameters were higher in patients with gestational diabetes mellitus at baseline than in controls. Ischemia-modified albumin levels were correlated with plasma glucose (p < 0.05). Variables of glycemic control and ischemia-modified albumin levels were significantly reduced at the 6th week. The effect of insulin treatment was generally better than diet therapy. Linear regression analysis showed that fasting plasma glucose was an independent determinant for IMA levels (β = 0.611, p = 0.035).Fetal outcome was similar except for macrosomia and Apgar score at 5 min. Conclusion.Serum ischemia-modified albumin levels were higher in gestational diabetes mellitus compared to normal pregnancy. Continuous subcutaneous insulin infusion consistently improved metabolic disorder control. Gestational diabetes mellitus women were associated to a higher risk of oxidative stress and pregnancy complications.     

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.     

Maternal BMI and HDL as predictors of pregnancy outcome in women with type 1 diabetes

Abstract

Objective: Diabetes in pregnancy is associated with increased risks of maternal as well as foetal complications.

Methods: Retrospective data on 96 women and their 96 newborns were anonymously statistically analysed to assess pregnancies of type 1 diabetes (T1D) women managed in our hospital in past nine years. The outcomes of the neonates were divided into three categories according to the clinical status, presence of congenital abnormalities and infant’s treatment.

Results: We found out that the outcome of newborn infants associated with maternal HbA1c before gestation as well as during the whole course of pregnancy (p?<?0.02 for all). Surprisingly, neonatal outcome was strongly associated with the maternal BMI (p?<?0.05). In our model, a lowering of BMI by one grade led to an 18% increase in the chance that the newborn will have no health problems. We did not observe an important worsening of chronic diabetic complications in mothers; however, regarding maternal clinical status, we found that preeclampsia occurrence was strongly and independently connected to HDL level (p?<?0.01).

Conclusion: Our data demonstrate that lower pregestational BMI could substantially improve T1D mothers' pregnancy outcome. Lower HDL levels in T1D mothers during pregnancy correlate with higher risk of preeclampsia development.     

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.     

Attitudes towards preconception care in Maltese women with type 1 diabetes mellitus

Introduction: The aim of this study was to assess the level of knowledge and awareness related to preconception care among Maltese women of reproductive age with type 1 diabetes mellitus (T1DM). Methods: Thirty-seven T1DM women, aged 12–30 years, were self-administered a questionnaire related to diabetes self-management and preconception care. The participants then underwent an educational intervention and re-took the same questionnaire. Results: Before the intervention, 26 participants (70%) claimed they did not have any knowledge about the preconception care of diabetes. Of the remaining 11 participants, the main reported source of information about diabetes care was the diabetologist (n = 8; 6.7%). The response rate was 70% (26 out of 37 participants completed the questionnaire after the educational intervention). Six of the participants who initially reported no preconception care knowledge claimed an increased awareness after the event. There was a statistically significant increase in the knowledge scores after the intervention. Conclusion: It is evident that there is a lack of awareness of the importance of pre-pregnancy planning to avoid pregnancy-related complications with diabetes. This emphasizes the need for more education and it is imperative for healthcare professionals to address these issues with adolescent female patients.     

Assessment of self monitoring of blood glucose (SMBG) and continuous subcutaneous insulin infusion (CSII) in diabetic pregnant women

We instructed pregnant women with insulin dependent diabetes mellitus (IDDM) or noninsulin dependent diabetes mellitus (NIDDM) how to monitor their own blood glucose concentrations and evaluated the efficiency and feasibility of continuous subcutaneous insulin infusion (CSII) therapy. Self-monitored glucose concentrations with a reflectance meter correlated with those of hospital laboratory measurements (hexokinase method) with a coefficient of more than 0.9. Glycosylated hemoglobin (HbA1) levels of the patients were normalized with insulin treatment based on the self-monitored glucose concentrations. In pregnant women with NIDDM who monitored their blood glucose concentrations before breakfast, the fasting glucose concentrations could be lowered by insulin administration and the duration of hospitalization could be shortened compared to non-monitored patients. Although diurnal variations were prominent in pregnant women with IDDM and precise control of their blood glucose concentrations was difficult with conventional insulin administration, even if the patients had monitored their glucose concentrations 7 times a day, the mean glucose concentrations and M values could be kept in the optimum range in patients treated with CSII. These methods have contributed to the improvement in maternal and infant complications.     

糖代谢异常孕妇胰岛素抵抗程度与巨大儿的关系

目的探讨糖代谢异常孕妇中胰岛素抵抗（IR）和胰岛β细胞功能的关系,以及胰岛素抵抗程度与巨大儿发生的关系。方法测定35例妊娠期糖耐量异常孕妇（GIGT）和12例妊娠期糖尿病孕妇（GDM）的空腹血糖、胰岛素,采用稳态模型评估法（HOMA）计算GIGT和GDM的胰岛素抵抗指数（HOMA-IR）和胰岛β细胞功能指数（HBCI）。结果GIGT、GDM两组孕妇HBCI无统计学差异（P〉0.05）,而HOMA-IR差异有统计学意义（P〈0.05）;HOMA-IR与巨大胎儿的发生没有显著相关性。结论GDM较GIGT孕妇存在更为明显的胰岛素抵抗,没有发现胰岛素抵抗指数与巨大儿的发生相关。     

Pregnancy planning in type 1 diabetic women improves glycemic control and pregnancy outcomes

Objective: Pregnancy in women with type 1 diabetes is associated with increased risks. The aim of this study was to evaluate the effect of pregnancy planning on outcomes of type 1 diabetic pregnancies.

Methods: We retrospectively assessed pregnancy outcomes of type 1 diabetic women who were patients of Diabetes Clinic of North Karelia hospital between 2000 and 2012. We evaluated the medical records of 73 women experiencing 145 pregnancies and data of their infants.

Results: Altogether 96 (66.2%) pregnancies were planned. HbA1c levels were significantly lower before and during the whole pregnancy when pregnancy was planned than if it was not planned (all p <0.001). Planned pregnancies resulted in significantly fewer congenital anomalies (p <0.001). Pregnancy planning reduced the age-adjusted risk of Cesarean sections (OR 0.25, p = 0.021). Pregnancy planning was associated with a reduced risk of adverse pregnancy outcomes (including miscarriages and congenital anomalies). This association was independent of age, HbA1c before pregnancy, smoking, hypertension, microvascular complications, and thyroid disease (OR 0.26; 95% CI 0.09, 0.76).

Conclusions: Pregnancy planning is beneficial for glycemic control and pregnancy outcomes of type 1 diabetic women. The benefit of pregnancy planning was independent of other risk factors for adverse pregnancy outcomes.     

Trends in prevalence and outcomes of pregnancy in women with pre-existing type I and type II diabetes

Objective  To describe recent trends in prevalence, outcomes and indicators of care for women with pre-existing type I or type II diabetes.
Design  Regional population-based survey.
Setting  All maternity units in the North of England.
Population  A total of 1258 pregnancies in women with pre-existing diabetes delivered between 1996 and 2004.
Methods  Data from the Northern Diabetic Pregnancy Survey. Outcome of pregnancy cross-validated with the Northern Congenital Abnormality Survey and the Northern Perinatal Mortality Survey.
Main outcome measures  Perinatal mortality, congenital anomaly and total adverse perinatal outcome (perinatal mortality and live births with congenital anomaly).
Results  The prevalence of pregestational diabetes increased from 3.1 per 1000 births in 1996–98 to 4.7 per 1000 in 2002–04 (test for linear trend, P < 0.0001), driven mainly by a sharp increase in type II diabetes. Perinatal mortality declined from 48 per 1000 births in 1996–98 to 23 per 1000 in 2002–04 ( P = 0.064). There was a significant reduction in total adverse perinatal outcome rate ( P = 0.0194) from 142 per 1000 in 1996–98 to 86 per 1000 in 2002–04. There were substantial improvements in indicators of care before and during pregnancy and in glycaemic control throughout pregnancy, but indicators of preconceptual care, such as use of folic acid, remained disappointing.
Conclusion  We observed improvements in pregnancy care and outcomes for women with diabetes in a region with an established audit and feedback cycle. There remains considerable scope for further improvement, particularly in periconceptual glycaemic control. The rising prevalence of type II diabetes presents a challenge to further improvement.     

Perinatal outcomes and macrosomia in a multi-ethnic population of women with type 2 diabetes

We reviewed pregnancy outcomes of women with type 2 diabetes giving birth over a six-year period, comparing the main ethnic groups. Asian women had significantly smaller babies and lower rates of macrosomia as defined by standard growth charts. Other outcomes were similar between the Asian, European and Polynesian women.     

Benefits, risks, costs, and patient satisfaction associated with insulin pump therapy for the pregnancy complicated by type 1 diabetes mellitus

OBJECTIVE: Glycemic control, perinatal outcome, and health care costs were evaluated among women with type 1 diabetes mellitus who began insulin pump therapy during pregnancy (group 1, n = 24), were treated with multiple insulin injections (group 2, n = 24), or were already using an insulin pump before pregnancy (group 3, n = 12). Patient satisfaction and continuation of pump therapy post partum were assessed. STUDY DESIGN: A retrospective review of maternal and neonatal medical records was performed, and a questionnaire was sent to patients after delivery. Patients in groups 1 and 2 were matched for age, age at onset and duration of diabetes mellitus, White class, and date of delivery. RESULTS: No differences in glycosylated hemoglobin A levels were observed among groups 1, 2 or 3 in the first, second, or third trimester. Patients in group 1 started pump therapy at a mean of 16.8 weeks' gestation, and 17 (70.8%) began therapy as outpatients. No deterioration in glycemic control was noted during the 2- to 4-week period after the start of pump treatment. Among the women in group 1 eight had at least one episode of severe hypoglycemia before starting pump therapy, but only one had such an episode after this treatment was begun. Two episodes of ketoacidosis occurred in group 1, and no episodes occurred in groups 2 and 3. No significant differences in perinatal outcomes or health care costs were observed among groups 1, 2, and 3. After delivery 94. 7% of the women in group 1 continued to use the pump because it provided better glycemic control and a more flexible lifestyle. Postpartum glycosylated hemoglobin A values were 7.2% in group 1 and 9.1% in group 2, a significant difference. CONCLUSIONS: Insulin pump therapy was initiated during pregnancy without a deterioration of glycemic control and was associated with maternal and perinatal outcomes and health care costs comparable to those among women who were already using the pump before pregnancy or who received multiple-dose insulin therapy. Women who began pump therapy in pregnancy were highly likely to continue pump use after delivery and preferred the flexible lifestyle that this treatment allowed.     

The prevalence of congenital malformations is still higher in pregnant women with pregestational diabetes despite near-normal HbA1c: a literature review

Aims/hypothesis: We assessed the association between congenital malformations and maternal hyperglycemia in pregnant women with pregestational (type 1 or type 2) diabetes and investigated if the rate of congenital malformations was similar in women with near-normal glycemic control compared to the background population. We also assessed the association between congenital malformations and maternal hyperglycemia in pregnant women with pregestational diabetes with special focus on women with near-normal HbA1c in early pregnancy.

Materials and methods: This is a literature review based on an electronic literature search of the databases PubMed, Cochrane, Embase and Web of Science conducted in July 2017 using the search terms diabetes, pregnancy, HbA1c or glycemic control and congenital anomaly or congenital anomaly. We included original papers in English published after 1997 with data on congenital malformations and HbA1c in at least 250 women with pregestational diabetes.

Results: Nine papers with in total 6225 women with type 1 diabetes and 2334 women with type 2 diabetes were included. The prevalence of congenital malformations was 6.4% in women with type 1 diabetes and 4.3% in women with type 2 diabetes and for the combined group of women with pregestational diabetes, the relative risk compared to the background population was 3.2. In women with HbA1c?Conclusions: In pregnant women with pregestational diabetes the prevalence of congenital abnormalities was threefold higher in women with pregestational diabetes compared to the background population. However, HbA1c below 53?mmol/mol (7.0%) in early pregnancy was also associated with a two times increased risk of congenital malformations compared to the background population.     

妊娠期糖尿病患者与正常孕妇妊娠中晚期胰岛素抵抗及胰岛B细胞功能观察

目的前瞻性纵向观察中期妊娠诊断为妊娠期糖尿病(GDM)患者及血糖正常孕妇在妊娠中晚期胰岛素抵抗及胰岛B细胞功能变化,并比较两者之间的差别。方法 2009年2月至2010年3月在中山大学孙逸仙纪念医院产前检查的82例孕妇于妊娠20～24周行葡萄糖耐量试验(OGTT)及胰岛素释放试验,诊断为GDM43例为GDM组,血糖正常的39例为对照组。于32～36周复查OGTT及胰岛素释放试验,纵向观察两组孕妇胰岛素抵抗及胰岛B细胞功能的变化。结果两组的胰岛B细胞分泌指数(HOMA-β)晚期妊娠均高于中期妊娠,时间主效应有统计学意义(F=7.863,P=0.007);GDM组的早期胰岛素分泌指数(△I30/△G30)中期妊娠及晚期妊娠均低于对照组,组间主效应差异有统计学意义(F=6.052,P=0.018),但GDM组从中期妊娠到晚期妊娠有所升高,而对照组逐渐下降。GDM组的血糖曲线下面积(AUCG)在中期妊娠及晚期妊娠均大于对照组(分别为P<0.0001,P=0.001),同时对照组的AUCG晚期妊娠显著高于中期妊娠(P=0.001);稳态模式胰岛素抵抗指数(HOMA-IR)及混合胰岛素敏感度的时间及组间主效应差异均无统计学意义。结论中晚期妊娠正常孕妇及GDM患者胰岛素抵抗均增加,后者胰岛素抵抗程度高于前者,胰岛B细胞代偿功能两者均增强;GDM组的早期胰岛素分泌功能较正常妊娠组下降。胰岛素抵抗和胰岛素分泌代偿不足是GDM发生、发展的重要机制。     

Beta cell function and insulin sensitivity in women with polycystic ovary syndrome: Influence of the family history of type 2 diabetes mellitus

Aim.?To study the impact of family history (FH) of type 2 diabetes mellitus on β-cell compensatory mechanism in women with polycystic ovary syndrome (PCOS).

Subjects and methods.?A total of 70 women with PCOS, 14 with first-degree relative with type 2 diabetes mellitus (T2DM) (FH+), 56 with negative FH of T2DM (FH?) and 72 age and BMI matched control healthy women (CNT) underwent oral glucose tolerance test (OGTT). Insulin resistance was evaluated as oral glucose index (OGIS); insulin and C-peptide secretion as the insulinogenic index in 30th min of OGTT.

Results.?Fasting blood glucose levels were significantly higher in FH+ than in FH? (p < 0.05). Fasting insulin was higher in FH+ than in CNT (p < 0.05). Fasting C-peptide was significantly higher in both FH? and FH+ than in CNT (p < 0.05 and p < 0.01, respectively). OGIS was lower in FH+ than in FH? or in CNT (p < 0.05). Insulinogenic index calculated from C-peptide values (II-Cp) was lower in FH+ than in CNT (p < 0.05). Adaptation index calculated from the values of OGIS and insulinogenic index was significantly lower in FH+ than in CNT or in FH? (p < 0.0001 and p < 0.01, respectively).

Conclusions.?Insulin resistance and defective early-phase insulin secretion is present only in those PCOS-affected subjects who had positive FH of T2DM.