Katrien Benhalima

Analysis of Pregnancy Outcomes Using the New IADPSG Recommendation Compared with the Carpenter and Coustan Criteria in an Area with a Low Prevalence of Gestational Diabetes

Aims. This paper aims to evaluate characteristics and pregnancy outcomes in women prior classified normal by Carpenter and Coustan criteria (old criteria) and now gestational diabetes (GDM) by the IADPSG criteria. Methods. Retrospective analysis of 6727 pregnancies is used. Using the old criteria, 222 had GDM (old GDM). Using the IADPSG criteria, 382 had GDM of which 160 had a normal glucose tolerance with the old criteria (new GDM). We compared the new GDM group with the old GDM group and women with normal glucose tolerance with both criteria (NGT group, 6345). Results. New GDM women were younger (31.6 ± 4.7 versus 33.3 ± 7.2 years, P = 0.010) than old GDM women. Caesarean section was performed in 30.5% of new GDM, in 32.4% of old GDM (P = 0.706), and in 23.3% of NGT women (P = 0.001). Large for gestational age occurred in 10.8% of new GDM, in 13.8% of old GDM (P = 0.473), and in 9.0% of NGT women (P = 0.099). Shoulder dystocia occurred in 3.9% of new GDM, in 3.2% of old GDM (P = 0.736), and in 1.4% of NGT women (P = 0.007). Conclusion. Using the IADPSG criteria, more women are identified as having GDM, and these women carry an increased risk for adverse gestational outcome compared to women without GDM.

Maternal obesity in Europe: where do we stand and how to move forward?: A scientific paper commissioned by the European Board and College of Obstetrics and Gynaecology (EBCOG)

Paralleling the global epidemic of obesity figures in the general population, the incidence of maternal obesity (BMI>30kg/m(2) at the start of pregnancy) has been rising over the last world. While most European countries do not systematically report obesity figures in their pregnant population, the prevalence of maternal obesity varies from 7 to 25% and seems strongly related to social and educational inequalities. Obesity during pregnancy represents an important preventable risk factor for adverse pregnancy outcomes and is associated with negative long-term health outcomes for both mothers and offspring. These effects are often aggravated by the high incidence of abnormal glucose tolerance and excessive gestational weight gain found in this group. The main controversies around the management of the obese pregnant women are related to (1) the value of repeated weighing during pregnancy, (2) the optimal gestational weight gain to advise and the lifestyle messages to deliver in order to achieve this, (3) the optimal strategy and timing of screening for gestational diabetes (GDM) and (4) the optimal timing and mode of delivery. These controversies are reviewed in this review, with the exception of screening for gestational diabetes that is discussed extensively elsewhere in this issue (Benhalima et al.). An agenda for research is proposed with the hope that it will catch the attention of policy-makers and funders and ultimately lead to the development of European-wide evidence-based guidelines for clinicians.

Insulin analogues in type 1 diabetes mellitus: getting better all the time

The treatment of type 1 diabetes mellitus consists of external replacement of the functions of β cells in an attempt to achieve blood levels of glucose as close to the normal range as possible. This approach means that glucose sensing needs to be replaced and levels of insulin need to mimic physiological insulin-action profiles, including basal coverage and changes around meals. Training and educating patients are crucial for the achievement of good glycaemic control, but having insulin preparations with action profiles that provide stable basal insulin coverage and appropriate mealtime insulin peaks helps people with type 1 diabetes mellitus to live active lives without sacrificing tight glycaemic control. Insulin analogues enable patients to achieve this goal, as some have fast action profiles, and some have very slow action profiles, which gives people with type 1 diabetes mellitus the tools to achieve dynamic insulin-action profiles that enable tight glycaemic control with a risk of hypoglycaemia that is lower than that with human short-acting and long-acting insulins. This Review discusses the established and novel insulin analogues that are used to treat patients with type 1 diabetes mellitus and provides insights into the future development of insulin analogues.

SGLT2-INHIBITORS: A NOVEL CLASS FOR THE TREATMENT OF TYPE 2 DIABETES INTRODUCTION OF SGLT2-INHIBITORS IN CLINICAL PRACTICE

Abstract Treatment of type 2 diabetes (T2DM) continues to present challenges, with significant proportion of patients failing to achieve and maintain glycemic targets. Despite the availability of many oral antidiabetic agents, therapeutic efficacy is offset by side effects such as weight gain and hypoglycemia. Therefore, the search for novel therapeutic agents with an improved benefit-risk profile continues. Recent research has focused on the kidney as a potential therapeutic target, especially because maximal renal glucose reabsorption is increased in T2DM. Under normal physiological conditions, nearly all filtered glucose is reabsorbed in the proximal tubule of the nephron, principally via the sodium-glucose cotransporter 2 (SGLT2). SGLT2- inhibitors are a new class of oral antidiabetics, which reduce hyperglycemia by increasing urinary glucose excretion independently of insulin secretion or action. Clinical results are promising with significant lowering of HbA1c without increased risk of hypoglycemia, reduction of body weight and reduction of systolic blood pressure. Dapagliflozin is the first highly selective SGLT2-inhibitor approved by the European Medecine Agency. Canagliflozin and empagliflozin are undergoing phase III trials. Actual safety issues are an increased risk for genital- and urinary tract infections and a possible increased risk for bladder and breast cancer. This led to refusal of dapagliflozin by the Food and Drug Administration (FDA). A large randomized control trial is therefore warranted by the FDA. This review provides an overview of the current evidence available so far on the therapeutic potential of the SGLT2-inhibitors for the treatment of T2DM.

Screening and management of gestational diabetes

Gestational diabetes (GDM) is a frequent medical condition during pregnancy. It is associated with an increased risk of complications for both the mother and the baby during pregnancy and post partum. The International Association of Diabetes and Pregnancy Study Groups (IADPSG) has proposed a new screening strategy for overt diabetes in pregnancy and screening for GDM. However, there is still a lack of international uniformity in the approach to the screening and diagnosis of GDM. Controversies include universal versus selective screening, the optimal time for screening, appropriate tests and cutoff values, and whether testing should be conducted in one or two steps. This review gives an update on screening for GDM and overt diabetes during pregnancy. We also give an overview on the medical and obstetrical management of GDM.

Sodium glucose transporter protein 2 inhibitors: focusing on the kidney to treat type 2 diabetes

Type 2 diabetes mellitus (T2DM) is increasing worldwide. Treatment of T2DM continues to present challenges, with a significant proportion of patients failing to achieve and maintain glycemic targets. Despite the availability of many oral antidiabetic agents, therapeutic efficacy is also offset by side effects such as weight gain and hypoglycemia. Therefore, the search for novel therapeutic agents with an improved benefit–risk profile continues. In the following review we focus on a novel class of oral antidiabetic drugs, the sodium glucose transporter protein 2 (SGLT2) inhibitors, which have unique characteristics. SGLT2 inhibitors focus on the kidney as a therapeutic target, where they inhibit the reabsorption of glucose in the proximal tubule, causing an increase in urinary glucose excretion. Doing this, they reduce plasma glucose independently of the β-cell function of the pancreas. SGLT2 inhibitors are effective at lowering hemoglobin A1c, but also induce weight loss and reduce blood pressure, with a low risk of hypoglycemia. In general, the SGLT2 inhibitors are well tolerated, with the most frequent adverse events being mild urinal and genital infections. Since their primary site of effect is the kidney, these drugs are less effective in patients with impaired kidney function but evidence is emerging that these drugs may also have a protective effect against diabetic nephropathy. This review focuses on the most extensively studied SGLT2 inhibitors dapagliflozin, canagliflozin and empagliflozin. Dapagliflozin and canagliflozin have already been approved for marketing by the US Food and Drug Administration. The European Medicines Agency has accepted all three drugs for marketing.

Survey by the European Board and College of Obstetrics and Gynaecology on screening for gestational diabetes in Europe

OBJECTIVES More uniformity is necessary in screening and diagnosis for gestational diabetes (GDM) across Europe. The European Board and College of Obstetrics and Gynaecology (EBCOG) has recently recommended to use the 2013 World Health Organization (WHO) criteria for the diagnosis of GDM. We evaluated the uptake of these EBCOG recommendations in guidelines for GDM screening across Europe. METHODS Between September and November 2015, an online survey on the current national or regional recommendations for GDM screening was directed to the 33 European countries that are members of EBCOG. RESULTS There was a response rate of 84.8% (28 countries). From Belgium, data were separately obtained from the Dutch-and the French-speaking parts and from the UK data were also obtained from Scotland, leading to data from 30 responders. The response rates were high in Central Europe (100%), Northern Europe (100%) and Southern Europe (85.7%) with lower response rates in Eastern Europe (71.4%). 82.1% of guidelines recommend screening for unknown diabetes at first prenatal visit and 67.9% recommend to screen for GDM before 24 weeks of pregnancy. All guidelines recommend to screen for GDM ≥24 weeks, based on risk factors in 64.3% and by universal screening in 35.7%. The most commonly used diagnostic criteria for GDM are the 2013 WHO criteria in 67.9%, the 1999 WHO criteria in 10.7%, the European Association for the Study of Diabetes criteria in 7.1% and the Carpenter & Coustan criteria in 7.1%. Of all societies advising the use of the 2013 WHO criteria, 52.6% recommends this based on risk factors, 10.5% recommends universal screening in a two-step strategy and 36.8% recommends a universal one-step approach with a 75g OGTT. CONCLUSIONS Our survey shows that the majority of European societies now advise to use the 2013 WHO criteria for GDM. However, only 36.8% recommends a universal one-step approach with a 75g OGTT with the majority of societies recommending screening based on risk factors. The use of common diagnostic criteria for GDM by the majority of societies is an important first step towards achieving uniformity in GDM screening across Europe.

Glucose intolerance in early postpartum in women with gestational diabetes: Who is at increased risk?

Women with a history of gestational diabetes (GDM) have an increased risk for developing type 2 diabetes in the years after the index pregnancy. Some women with GDM already develop glucose intolerance in early postpartum. The best screening strategy for glucose intolerance in early postpartum among women with a history of GDM is still debated. We review the most important risk factors of women with GDM to develop glucose intolerance within one year postpartum. We also discuss the current recommendations for screening in early postpartum and the many challenges to organize postpartum follow up in primary care.

Screening for pregestational and gestational diabetes in pregnancy: a survey of obstetrical centers in the northern part of Belgium

BackgroundThere is lack of consensus concerning the best screening strategy for gestational diabetes (GDM). The aim of our survey was therefore to investigate attitudes and practices of all obstetrical centers in the northern part of Belgium regarding screening for pregestational diabetes in early pregnancy and screening for GDM. We also aimed to identify the penetrance of the ‘International Association of Diabetes in Pregnancy Study Groups’ (IADPSG) screening strategy for GDM.MethodsThe survey was conducted from May 2012 till January 2013. The survey was distributed to every obstetrical center in the northern part of Belgium by email and/or mail with reminders by phone and personal contact.ResultsFrom the 65 obstetrical centers, 69% responded. Of all centers, 27% had a structured database on the number of women with GDM. Of all centers, 82% screened for pregestational diabetes in early pregnancy and 56% of centers screened for GDM before 24 weeks. Screening before 24 weeks was mostly based on risk factors. Screening for GDM after 24 weeks, was done universally in 87% of centers. The mean estimated prevalence of GDM was 7 ± 5%. The most commonly used screening strategy was a two-step approach with a glucose challenge test (GCT) and 100 g oral glucose tolerance test (OGTT), used by 56% of centers, with 23 centers using the Carpenter & Coustan criteria. The 75 g OGTT with the IADPSG criteria was used by 33% of centers but 4 of these centers still used a GCT before proceeding to the full OGTT.ConclusionsThis survey demonstrates that in the northern part of Belgium, there still is a large variation in screening strategy for pregestational diabetes in early pregnancy and GDM. Only 25% of centers have already implemented the one-step IADPSG screening strategy.

The importance of glycemic control: how low should we go with HbA1c? Start early, go safe, go low

Epidemiologic data indicate a continuous relationship between hemoglobin A1c (HbA1c) and risk for microvascular and macrovascular complications of diabetes. Intensive glycemic control reduces risk of microvascular complications in Type 1 and Type 2 diabetes, and long-term treatment and follow-up studies have shown that initial intensive control is associated with reduced cardiovascular risk. Recent intervention trials in older, high-risk patients with Type 2 diabetes have not shown a benefit of intensive control in reducing cardiovascular risk over a rather short-term follow-up period of up to 5 years, with some data indicating that intensive control accompanied by hypoglycemia is detrimental in patients with high cardiovascular risk. Indeed, hypoglycemia with current antidiabetic agents--primarily insulin and sulphonylureas--is the main limiting factor in achieving desirable levels of glycemic control. Still, the goal in treating both Type 1 and Type 2 diabetes should be to safely get HbA1c as close to normal as possible. In Type 2 diabetes, this goal should be tempered for the time being in patients with shorter life expectancy or co-existing cardiovascular disease or other co-morbidities, in whom a target of 7.0-7.5% may be advisable until we can demonstrate that lower targets in such patients can be safely achieved. Newer agents with lower risk of hypoglycemia--e.g., insulin analogues, incretin mimetics and incretin enhancers-may form an integral component of strategies for safely achieving lower HbA1c levels.