Oded Langer’s research while affiliated with The University of Tennessee Medical Center at Knoxville and other places

The obesity and diabetes epidemic is an unintended consequence of economic, social and technological changes. In non-pregnancy, people identified as high risk to develop type 2 diabetes may delay progression by 30 to 70% with lifestyle interventions and pharmacological agents. In pregnancy, lifestyle interventions has been the primary focus to prevent fetal short and long term complications that may evolve into substantial weight gain and gestational diabetes mellitus (GDM). The dilemma for obstetricians is whether diabetes and obesity can be prevented and not simply treated after the fact. Interventions after women become pregnant may be too late to see the kinds of meaningful improvements in child and maternal health because there is a short interval from GDM diagnosis to delivery. Therefore, future efforts need to incorporate quality research, lifestyle interventions that designate time of initiation and duration during pregnancy, the preventative intervention of a pre-pregnant "fourth trimester" coupled with the concept of precision medicine so that there is the potential to make the "impossible dream" a reality.

Controversies persist over the most efficacious pharmacologic treatment for gestational diabetes mellitus. For purposes of accuracy in this article, the individual American College of Obstetricians and Gynecologists Practice Bulletin and American Diabetes Association Standards of Medical Care positions on each issue are quoted and then deliberated with evidence of counter claims presented in point/counterpoint. This is a review of all the relevant evidence for the most holistic picture possible. The main issues are (1) which diabetic drugs cross the placenta, (2) the quality of evidence and data source validity, (3) the rationale for the designation of glucose control as the primary outcome in gestational diabetes mellitus, and (4) which drugs (metformin, glyburide, or insulin) are most effective in improving secondary outcomes. The concept that 1 drug fits all, whether it be insulin, glyburide, or metformin, is a fallacy. Different drugs provide certain benefits but not all the benefits and not to all patients. In addition, the steps in the gestational diabetes mellitus management decision path and the current cost of the use of insulin, glyburide, or metformin are addressed. In the future, we must consider studying the potential of diabetic drugs that currently are used in nonpregnancy and incorporating the concept of precision medicine in the decision tree to maximize pregnancy outcomes.

The Diabetes in Pregnancy Study Group of North America (DPSG-NA) was founded in 1997 in San Antonio, Texas, out of the recognition that the field of maternal-fetal medicine should support and conduct research to address the specialized needs of pregnant women with type 1, type 2, or gestational diabetes mellitus. Since its inception, the DPSG-NA meetings have become a vehicle for the dissemination of data, gathered through collaboration among basic, translational, and clinical researchers and care centers, both in the United States and abroad. Although the meetings cover a range of topics related to diabetes in pregnancy, they have often highlighted a major, timely issue. Utilizing presentations, roundtable discussions, and debates, members of the DPSG-NA discussed the latest research, treatments, and approaches to significantly improve the health and wellbeing of pregnant women with diabetes and their offspring. The following commentary highlights the major contributions of each meeting. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Background Glyburide has replaced insulin as the first line of therapy in the treatment of gestational diabetes in the United States. Glyburide and metformin therapies were reported to be comparable to insulin yet also cost-effective, patient-friendly, and potentially compliance-enhancing. Recently, the efficacy of the use of these oral hypoglycemic drugs has been questioned. In this review, the questionable concerns will be addressed: Which diabetic drug(s) cross the placenta? What is the quality of evidence and the data source validity? Which treatment modalities are most effective in reducing the primary outcome in GDM? Which drug is most effective in improving secondary outcomes? Findings This review documents the methodological issues in study design that have impacted the results for the provision of health care interventions in GDM. The review summarizes the contents of the articles qualitatively and assesses the theoretical and empirical evidence. Multiple types of studies exist and every study design serves a specific purpose. Different study designs addressing the same question can yield varying results. The risk of presenting uncertain results without categorically knowing the direction and magnitude of the effect holds true for both randomized and nonrandomized controlled trials. The review further emphasizes the importance of achieving the targeted levels of glycemic control. Conclusion The implications of this review are critical to addressing the current gaps in the literature on the efficacy of the use of oral hypoglycemic agents in GDM. The emphasis needs to be placed on patient treatment in order to manage hyperglycemia to reduce fetal and maternal morbidity. In this regard, we need to delineate proper outcome criteria that will reflect disease severity and treat using appropriate pharmacological therapy.

To evaluate treatment effectiveness (diet alone, insulin or glyburide) on maternal weight gain in gestational diabetes (GDM). GDM patients were treated with diet alone, insulin or glyburide. Weight gain was stratified into: prior to GDM diagnosis, from diagnosis to delivery and total pregnancy weight gain. Good glycemic control was defined as mean blood glucose ≤105 mg/dl and obesity as Body Mass Index (BMI) ≥ 30 kg/m(2), overweight BMI 25-29 kg/m(2) and normal < 25 kg/m(2). Total weight gain was similar in all the treatment groups. Two-thirds of weight gain occurred prior to diagnosis (diet 85%, insulin 67% and glyburide 78%). Post-diagnosis, patients on diet alone gained less weight than those on insulin or glyburide (p < 0.001); insulin-treated patients showed greater weight gain than glyburide-treated patients (p < 0.001). Patients on diet with good glycemic control showed less weight gain after diagnosis than patients on insulin or glyburide (2.8 ± 13, 6.6 ± 10, 5.2 ± 7.9 lbs, respectively, p < 0.02). Poorly-controlled patients, regardless of treatment, had similar patterns of weight gain throughout pregnancy. Patterns of maternal weight gain in GDM pregnancies are associated with treatment modality and level of glycemic control.

Abstract Objective: To examine impact on perinatal outcome of untreated gestational diabetes (GDM) and non-diabetics stratified by BMI. Research design and methods: This is a secondary analysis of our investigation of the consequences of not treating GDM. We evaluated 555 untreated GDMs matched to 1100 non-diabetics. BMI was determined using subjects' recalled pre-pregnancy weight. A primary composite variable consisted of stillbirth, neonatal macrosomia/LGA, neonatal hypoglycemia, erythrocytosis, and hyperbilirubinemia. Secondary outcomes included shoulder dystocia, respiratory complications, cesarean delivery and pregnancy-related hypertension. Results: Normal weight category revealed an approximate 2-folds increase for composite outcome and LGA and a 7-folds increase in metabolic complications. The overweight untreated group showed composite outcome, LGA and metabolic complications 2-3 folds higher and induction of labor 5-folds higher. For obese untreated GDMs, significantly higher rates of composite outcome, LGA and metabolic complications, induction of labor and cesarean delivery were 10-folds, 3-folds, 5-folds, 4-folds, and 9-folds, respectively. Perinatal outcome for normal weight untreated GDM was similar to obese non-diabetics. Conclusions: Maternal obesity and GDM are independently associated with adverse pregnancy outcome. The combination has a greater impact than each one alone. However, level of glycemia contributes a greater portion to the adverse pregnancy equation.

Lowering glucose is of pivotal importance in the treatment of diabetes in pregnancy. A spectrum of different glucose thresholds can be established and used appropriately to prevent each complication. This article outlines the concept of normality and what definition of normality should be used to evaluate the relationship between the level of glycemia and perinatal outcome.

To date, The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria for the diagnosis of gestational diabetes mellitus (GDM) have not been analyzed systematically for medical, social, and economic ramifications if used in substitution for the current GDM diagnostic criteria. The IADPSG dependence on expert opinion and consensus rather than on rigorously obtained outcome measures is concerning given the dramatic changes in clinical intervention and medical-resource reallocation that would follow their wide adoption. This commentary attempts to highlight needed research as well as the key knowledge gaps that should prevent adoption of the revised criteria until their effect on perinatal outcomes and health care costs is determined. In light of the overall, ethnic, and regional variation in GDM prevalence and the demands of increased GDM diagnosis on clinical resources, it may not be realistic and practical to impose universal strategies and standards for diagnosis. The newly proposed criteria may affect medical care negatively, unnecessarily stigmatize patients with a "sick label," and adversely affect health care costs without ensuring the desired improvements in maternal and neonatal outcomes. This commentary serves as a caution to not promote a new endeavor until it has been compared rigorously with current practice and its implications are understood fully.

Abstract The new criteria for diagnosis of gestational diabetes mellitus proposed by the International Diabetes in Pregnancy Consensus group (IADPSG) transports back the controversy and the lack of agreement to the frontlines. The recommended criteria are based on results of the observational hyperglycemia and adverse pregnancy outcome study (HAPO). These criteria will increase the frequency of gestational diabetes diagnosis by 2-8 fold, depending upon ethnicity, and prevalence of obesity. Do the costs and implied resources justify using the proposed endpoints that will define pregnancy outcome and severity especially when the appropriate outcomes and odds ratio used to define the diagnosis are questionable? Furthermore, due to the large disparity around the globe in relation to the prevalence of GDM raises the question if single diagnostic criteria can be made to fit all?!? The current review analyzes the risks, costs and benefits that may influence the rate of GDM in relation to the worldwide prevalence.