The emerging role of metformin in gestational diabetes mellitus

Metformin use during pregnancy is controversial and there is disparity in the acceptance of metformin treatment in women with gestational diabetes mellitus (GDM) in Australia. Despite short term maternal and neonatal safety measures, the placental transfer of metformin during GDM treatment and the absence of long‐term safety data in offspring has regulators and prescribers cautious about its use. To determine the current role in GDM management, this literature review describes the physiological changes that occur in GDM and other forms of diabetes in pregnancy (DIP) and international changes in guidelines for GDM diagnosis. Management options are considered, with a focus on the evolving evidence for metformin, its mechanism of action, the maternal, foetal and neonatal outcomes associated with its use and benefit vs risk when compared with the current gold standard, insulin. Investigation reveals a favourable balance of evidence to support the safety and long‐term benefits, to mother and child, of using metformin as an alternate to insulin for treatment of GDM. Recent findings of the gastrointestinal‐directed action of metformin are at least as important as the hepatic effect and the availability of a novel delayed‐release metformin dose form to exploit this new information provides a product and therapeutic strategy ideally suited to the use of metformin in GDM.     

The association of gestational diabetes mellitus with fetal birth weight

Aims

Gestational diabetes mellitus (GDM) and different time-point glucose levels might have different effects on fetal birth weight. The aim of this study was to further evaluate the associations of GDM and different time-point blood glucose levels with fetal birth weight in a prospective cohort study.

Predictors of metformin failure in gestational diabetes mellitus (GDM)

Introduction and objective

The role of metformin in gestational diabetes mellitus (GDM) is also increasing. However, almost half of metformin-treated women required additional insulin. Therefore, identifying the characteristics of these women may help define optimal therapeutic strategy.

糖化血红蛋白不适用于妊娠糖尿病的筛查和诊断

目的 探讨糖化血红蛋白(HbA1c)在妊娠糖尿病(GDM)筛查与诊断中的价值. 方法 对1815例50g葡萄糖负荷试验(GCT)阳性的孕妇同时测定3hOGTT及HbA1c,比较糖耐量正常(NGT)组、妊娠糖耐量减低(GIGT)组和GDM组HbA1c分布情况,并计算ROC曲线下面积(AUC). 结果 3组HbA1c分布几乎重叠,ROC曲线下面积(AUC)为0.658,95%可信区间为[0.626, 0.690]. 结论 HbA1c不适用于GDM的早期筛查与诊断.     

Maternal serum and fetal cord blood irisin levels in gestational diabetes mellitus

Aim

To investigate the relationship between maternal and cord blood irisin in gestational diabetes mellitus (GDM).

Methods

Twenty women with GDM and 20 pregnant women with uncomplicated pregnancies were recruited for this case–control study. Maternal serum irisin and cord blood irisin levels were measured by enzyme-linked immunosorbent assay kit at the time of birth. The association of maternal serum and cord blood irisin levels with metabolic parameters was analyzed.

Results

Women with GDM had significantly lower mean serum irisin levels compared to control group (258.3 ± 127.9 vs. 393 ± 178.9 ng/ml, p < 0.05). Mean cord blood irisin levels for GDM and control groups were not significantly different (357.2 ± 248.0 vs. 333.2 ± 173.4 ng/ml, p > 0.05). No significant differences were found in terms of maternal age, gestational week at birth, BMI at birth, birth weight, neonatal height, systolic and diastolic blood pressure between the groups as well (p > 0.05). Serum irisin level was negatively correlated with BMI at birth and HOMA-IR (r = −0.401, p = 0.010; r = −0.395, p = 0.012, respectively). No correlations between irisin levels and others parameters were found in both groups.

Conclusions

Maternal serum irisin levels of patients with GDM are significantly lower compared with non-GDM controls. However, no significant difference was found between cord blood irisin levels of patients with GDM and healthy pregnant women.     

The impact of restricted gestational weight gain by dietary intervention on fetal growth in women with gestational diabetes mellitus

Aims/hypothesis

We aimed to investigate the impact of maternal gestational weight gain (GWG) during dietary treatment on fetal growth in pregnancies complicated by gestational diabetes (GDM).

Methods

This was a retrospective cohort study of 382 women consecutively diagnosed with GDM before 34 weeks’ gestation with live singleton births in our centre (Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark) between 2011 and 2017. The women were stratified into three groups according to restricted (53%), appropriate (16%) and excessive (31%) weekly GWG during dietary treatment (using the Institute of Medicine guidelines) to estimate compliance with an energy-restricted ‘diabetes diet’ (6000 kJ/day [1434 kcal/day], with approximately 50% of energy intake coming from carbohydrates with a low glycaemic index, and a carbohydrate intake of 175 g/day). Insulin therapy was initiated if necessary, according to local clinical guidelines.

Results

Glucose tolerance, HbA_1c, weekly GWG before dietary treatment (difference between weight at GDM diagnosis and pre-pregnancy weight, divided by the number of weeks) and SD score for fetal abdominal circumference were comparable across the three groups at diagnosis of GDM at 27⁶?±?5¹ weeks (gestation time is given as weeks^days). The women were followed for 10⁰?±?5¹ weeks, during which 54% received supplementary insulin therapy and the average (mean) GWG during dietary treatment was 0 kg, 3 kg and 5 kg in the three groups, respectively. Excessive weekly GWG during dietary treatment, reflecting poor dietary adherence was associated with increasing HbA_1c (p?=?0.014) from diagnosis of GDM to late pregnancy and infants with a birthweight-SD score of 0.59?±?1.6. In contrast, restricted weekly GWG during dietary treatment, reflecting strict dietary adherence, was associated with decreasing HbA_1c (p?=?0.001) from diagnosis of GDM to late pregnancy and infants with a birthweight-SD score of 0.15?±?1.1, without increased prevalence of infants born small for gestational age. Excessive GWG during dietary treatment and late-pregnancy HbA_1c were identified as potentially modifiable clinical predictors of infant birthweight-SD score (p?=?0.02 for both variables) after correction for confounders.

Conclusions/interpretation

Restricted GWG during dietary treatment was associated with healthier fetal growth in women with GDM. GWG during dietary treatment and late-pregnancy HbA_1c were identified as potentially modifiable clinical predictors of infant birthweight-SD score.

     

Progesterone in gestational diabetes mellitus: guilty or not guilty?

Insulin resistance is one of the metabolic changes in pregnancy, but only a fraction of women develop overt impaired glucose tolerance or frank diabetes. Most women are able to compensate this altered metabolic state by increasing the amount of insulin produced by the pancreatic beta cells. Progesterone might well be the key to the development of gestational diabetes. Previously high progesterone levels have already been shown to be correlated with the development of glucose abnormalities in pregnancy and now, in a new paper, progesterone receptor-knockout mice are found to have improved glucose tolerance. These mice showed increased insulin secretion, which is probably linked to the presence of increased numbers of beta cells in their pancreas. Is progesterone therefore the 'ultimate bad guy', prohibiting normal adaptation of the pancreatic beta-cell reserve during pregnancy?     

Birth weight influence on the subsequent development of gestational diabetes mellitus

Epidemiological observations have suggested a relationship between type 2 diabetes and a low or high birth weight. However, there are many confounding variables and problems with retrospective data collection. The study of women with gestational diabetes mellitus (GDM), who are likely to develop type 2 diabetes in the future, may help clarify these observations. Women diagnosed as suffering from GDM (n=162) were included in the study if their own birth weight data were available. The birth-weight distribution of the general population was obtained from published data for the same period. A family history of diabetes prevalence was assessed from medical records for the 162 GDM subjects, and by direct interview of 250 non-diabetic pregnant controls. The birth-weight distribution of women with GDM, when normalized to that of the general population, showed a statistically significant U-shape with a greater proportion of GDM women having low (1000–2000 g) or high (>4500 g) birth weight. Compared to non-diabetic pregnant controls, a statistically higher proportion of GDM women had a maternal family history of diabetes; the mean birth weight of these women was also statistically higher than that of GDM women with no family history of diabetes. No such differences were noted among women with a paternal family history. These data suggest that the intrauterine millieur Interieur, whether one of nutritional deprivation or one of nutritional plenty, results in changes in pancreatic development and peripheral response to insulin that may lead to adult-onset GDM and type 2 diabetes. Genetic predisposition, unless determined by mitrochondrial genetic material, does not apparently have any part in determining birth weight. Received: 5 August 2002 / Accepted in revised form: 12 February 2003 Correspondence to C. Savona-Ventura     

妊娠糖尿病发病机制研究进展

妊娠糖尿病(GDM)主要指妊娠期首次发现的糖耐量异常.GDM与非妊娠期的糖尿病都是遗传因素与环境因素共同作用所致的多基因复杂疾病,其发病机制涉及遗传易感性、胰岛素抵抗和分泌缺陷、慢性炎性反应等.而且,GDM病史是女性产后发展为糖尿病的高危因素.因此,深入了解GDM的发病机制具有重要意义.     

妊娠糖尿病的药物治疗

妊娠糖尿病是在妊娠过程中首次发现的任何程度的糖耐最异常,其发病机制与多种因素相关.妊娠期间血糖水平对母体、妊娠结局及围产儿的预后有着重要的影响.治疗妊娠糖尿病的药物选择要求能够有效控制血糖,及对胎儿影响小,低血糖事件少,患者依从性好等.目前治疗妊娠糖尿病的药物仍以胰岛素为主,但部分口服降糖药也逐渐进入人们的视野.现就妊娠糖尿病的药物治疗进行概述.     

Hemostatic changes in gestational diabetes mellitus

The purpose was to characterize the hemostatic changes in women with gestational diabetes mellitus (GDM). In this case–control study, 50 women with newly diagnosed GDM at 24–28 weeks of pregnancy and 41 normal pregnant women, matched for age, body mass index, and gestational age, were enrolled. Anthropometric, metabolic patterns, coagulation parameters, and plasminogen were measured in each subject. Plasma fibrinogen levels, plasminogen, and von Willebrand factor (vWF) activities were significantly higher in patients with GDM as compared to normal pregnant women (p < 0.001, p < 0.001, and p < 0.05, respectively). Although protein S was significantly elevated in diabetic group (p < 0.05), free protein S was similar in both groups. Coagulation factors VIII and IXa were significantly higher in patients with GDM (p < 0.001 and p < 0.01, respectively). In the group with GDM, factor VIII was positively correlated with HbA1c (r = 0.192, p < 0.001). A weak but significant negative correlation was observed between protein S and fasting glucose (r =−0.006, p < 0.05). GDM potentiates the alteration in coagulation and fibrinolysis during normal pregnancy. The question of whether the hemostatic balance is unchanged or shifts toward a hypercoagulable status remains unanswered.

     

Circulating Pro-Neurotensin in gestational diabetes mellitus

Background and aims

Pro-Neurotensin (NT), a stable surrogate parameter of NT, has recently been introduced as a peptide predicting the development of obesity, diabetes mellitus, cardiovascular diseases, and cardiovascular mortality. However, regulation of Pro-NT in gestational diabetes mellitus (GDM) remains uninvestigated.