Impact of bariatric surgery on anthropometric, metabolic, and reproductive outcomes in polycystic ovary syndrome: a systematic review and meta-analysis.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in females. Modest weight loss improves reproductive and metabolic PCOS features. While lifestyle modifications and pharmacotherapies remain first-line weight loss strategies, bariatric surgery is emerging as a potentially effective treatment. We performed a systematic review and meta-analysis of published literature to examine the impact of bariatric surgery in PCOS to inform the 2023 International PCOS Evidence-based Guidelines. Electronic databases were searched for observational studies and trials comparing pharmacologic or lifestyle treatments to bariatric surgery in women with PCOS or bariatric surgery in women with or without PCOS. Anthropometric, reproductive, hormonal, and metabolic outcomes were included and, where possible, meta-analyzed using random-effects models. Risk of bias and evidence quality were assessed. Ten studies were included involving 432 women with and 590 women without PCOS. Comparisons between bariatric surgery and pharmacologic or lifestyle treatments were only reported in one study each, and most reproductive outcomes were limited to a single study; therefore, meta-analyses could not be performed. Meta-analysis found that women with PCOS experience similar improvements in anthropometric, hormonal, and metabolic outcomes after bariatric surgery compared to those without PCOS. Existing research is limited and of low quality with high risk of bias, especially in comparison to existing PCOS treatments and with respect to reproductive outcomes including pregnancy, highlighting the need for additional studies to inform clinical recommendations.

Precision gestational diabetes treatment: a systematic review and meta-analyses.

BACKGROUND: Gestational Diabetes Mellitus (GDM) affects approximately 1 in 7 pregnancies globally. It is associated with short- and long-term risks for both mother and baby. Therefore, optimizing treatment to effectively treat the condition has wide-ranging beneficial effects. However, despite the known heterogeneity in GDM, treatment guidelines and approaches are generally standardized. We hypothesized that a precision medicine approach could be a tool for risk-stratification of women to streamline successful GDM management. With the relatively short timeframe available to treat GDM, commencing effective therapy earlier, with more rapid normalization of hyperglycaemia, could have benefits for both mother and fetus. METHODS: We conducted two systematic reviews, to identify precision markers that may predict effective lifestyle and pharmacological interventions. RESULTS: There was a paucity of studies examining precision lifestyle-based interventions for GDM highlighting the pressing need for further research in this area. We found a number of precision markers identified from routine clinical measures that may enable earlier identification of those requiring escalation of pharmacological therapy (to metformin, sulphonylureas or insulin). This included previous history of GDM, Body Mass Index and blood glucose concentrations at diagnosis. CONCLUSIONS: Clinical measurements at diagnosis could potentially be used as precision markers in the treatment of GDM. Whether there are other sensitive markers that could be identified using more complex individual-level data, such as omics, and if these can feasibly be implemented in clinical practice remains unknown. These will be important to consider in future studies.

Gestational diabetes (GDM) is high blood sugar first detected during pregnancy. Normalizing blood sugar levels quickly is important to avoid pregnancy complications. Many women achieve this with lifestyle changes, such as to diet, but some need to inject insulin or take tablets. We did two thorough reviews of existing research to see if we could predict which women need medication. Firstly we looked for ways to identify the characteristics of women who benefit most from changing their lifestyles to treat GDM, but found very limited research on this topic. We secondly searched for characteristics that help identify women who need medication to treat GDM. We found some useful characteristics that are obtained during routine pregnancy care. Further studies are needed to test if additional information could provide even better information about how we could make GDM treatment more tailored for individuals during pregnancy.

Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine.

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.

A Randomized Trial of Closed-Loop Insulin Delivery Postpartum in Type 1 Diabetes.

OBJECTIVE: This study aimed to evaluate the efficacy of closed-loop insulin delivery postpartum. RESEARCH DESIGN AND METHODS: In this open-label, randomized controlled trial, postpartum individuals with type 1 diabetes were randomized to hybrid closed-loop insulin delivery with the MiniMed 670G/770G system in automode or sensor-augmented pump therapy in the first 12-weeks postpartum followed by a continuation phase with closed-loop insulin delivery for all until 24 weeks postpartum. RESULTS: Eighteen participants (mean ± SD age 32 ± 3.5 years, diabetes duration 22 ± 7.3 years, and early pregnancy HbA1c 52 ± 6.8 mmol/mol [6.9 ± 0.9%]) completed 24 weeks of postpartum follow-up. In the randomized phase, percent time in range 70-180 mg/dL (3.9-10 mmol/L) did not differ between groups (79.2 ± 8.7% vs. 78.2 ± 6.0%; P = 0.41). Participants randomized to closed-loop insulin delivery spent less time <70 mg/dL (3.9 mmol/L) and <54 mg/dL (3.0 mmol/L) (1.7 ± 0.8% vs. 5.5 ± 3.3% [P < 0.001] and 0.3 ± 0.2% vs. 1.1 ± 0.9% [P = 0.008]). Time >180 mg/dL (10 mmol/L) was not different between groups (18.7 ± 8.8% vs. 15.9 ± 7.7%; P = 0.21). In the continuation phase, those initially randomized to sensor-augmented pump therapy had less time <70 mg/dL after initiation of closed-loop insulin delivery (5.5 ± 3.3% vs. 3.3 ± 2.2%; P = 0.039). The closed-loop group maintained similar glycemic metrics in both study phases. There were no episodes of diabetic ketoacidosis or severe hypoglycemia in the randomized or continuation phase in either group. CONCLUSIONS: Women randomized to closed-loop insulin delivery postpartum had less hypoglycemia than those randomized to sensor-augmented pump therapy. There were no safety concerns. These findings are reassuring for use of closed-loop insulin delivery postpartum because of its potential to reduce hypoglycemia.

A Primer on Systematic Review and Meta-analysis in Diabetes Research.

A systematic review is a rigorous process that involves identifying, selecting, and synthesizing available evidence pertaining to an a priori-defined research question. The resulting evidence base may be summarized qualitatively or through a quantitative analytic approach known as meta-analysis. Systematic review and meta-analysis (SRMAs) have risen in popularity across the scientific realm including diabetes research. Although well-conducted SRMAs are an indispensable tool in informing evidence-based medicine, the proliferation of SRMAs has led to many reviews of questionable quality and misleading conclusions. The objective of this article is to provide up-to-date knowledge and a comprehensive understanding of strengths and limitations of SRMAs. We first provide an overview of the SRMA process and offer ways to identify common pitfalls at key steps. We then describe best practices as well as evolving approaches to mitigate biases, improve transparency, and enhance rigor. We discuss several recent developments in SRMAs including individual-level meta-analyses, network meta-analyses, umbrella reviews, and prospective meta-analyses. Additionally, we outline several strategies that can be used to enhance quality of SRMAs and present key questions that authors, editors, and readers should consider in preparing or critically reviewing SRMAs.

Changes in Prevalence and Incidence at the Population Level of Type 2 Diabetes in First Nations and All Other Adults in Manitoba.

OBJECTIVES: The prevalence of type 2 diabetes (T2D) is increasing and Indigenous populations are at highest risk. Canadian data are crucial for health planning. METHODS: Population-based, de-identified, linked databases were used to calculate the incidence and prevalence of T2D for registered adult First Nations Manitobans and all other adult Manitobans from 2011-2012 to 2016-2017. RESULTS: The crude prevalence of T2D increased over the 6-year study period. The crude incidence of T2D for First Nations Manitobans dropped from 11.02 to 9.74 per 1,000 person-years at risk and the crude incidence for all other Manitobans did not change; in the last 2-year period, it was 6.53 per 1,000 person-years at risk. When incidence was stratified by age, the results differed between the younger and older age groups. For First Nations individuals, the adjusted incidence of T2D for those <30 years old increased over time, with no change in those ≥30 years old. For all other Manitobans, crude incidence increased over time in the young and middle age ranges (i.e. 18 to 29 years and 35 to 44 years, respectively). Both age- and sex-adjusted relative prevalence (adjusted rate ratio [aRR], 3.47; 95% confidence interval [CI], 2.56 to 4.70) and incidence (aRR, 1.97; 95% CI, 1.51 to 2.56) were higher for First Nations Manitobans. CONCLUSIONS: The prevalence of T2D continues to increase and disproportionately affects First Nations populations. Furthermore, the incidence is increasing in the younger age groups. Prevention and screening programs must include younger age groups and partner with First Nations communities.

Treating to Target Glycaemia in Type 2 Diabetes Pregnancy.

There is an increasing awareness that in those who develop early-onset (18-39 years) adult type 2 diabetes, an increase in insulin resistance, deterioration in beta-cell, and clustering of cardiovascular risk factors are particularly pronounced. Pregnant women with type 2 diabetes have additional risk factors for serious adverse pregnancy outcomes as well as added barriers regarding healthcare access before, during, and after pregnancy. Compared to pregnant women with type 1 diabetes, those with type 2 diabetes are older, have higher body mass index (BMI), with more metabolic comorbidities and concomitant medications, are more likely to belong to minority ethnic groups, and live in the highest areas of socio-economic deprivation. Approximately, one in seven pregnant women with type 2 diabetes (median age 34 years) are taking ACE-inhibitors, statins (13%), and/or other potentially harmful diabetes therapies (7%). Fewer than one in four are taking a high dose of folic acid before pregnancy, which may suggest that planning for pregnancy is not a priority for women themselves, their healthcare professionals, or the healthcare system. Knowledge of the epidemiology, pathophysiology, and unique management considerations of early-onset type 2 diabetes is essential to providing evidence-based care to pregnant women with type 2 diabetes. This narrative review will discuss contemporary data regarding type 2 diabetes pregnancy outcomes and the increasing recognition that different types of diabetes may require different treatment strategies before, during, and after pregnancy.

Missed antenatal diabetes care appointments and neonatal outcomes for pregnancies with Type 1 and Type 2 diabetes.

BACKGROUND: There is limited information regarding the association between missed appointments and neonatal outcomes for diabetes in pregnancy. STUDY METHODS: This retrospective live birth cohort included pregnant women with Type 1 or 2 diabetes who attended specialized clinics from 2008 to 2020. The association between at least one missed antenatal diabetes appointments and outcomes were assessed using logistic regression and reported as adjusted odds ratios (aOR) (95% confidence interval). Mediation analyses were conducted to examine if above target HbA1c mediated these relationships. RESULTS: The cohort included 407 and 902 women with Type 1 and 2 diabetes, respectively, of whom 25.1% and 34.5% missed at least one appointment. Women with Type 1 diabetes who missed an appointment were more likely to have a caesarean section (aOR 1.95 [1.15, 3.31]) and their babies more likely to be admitted to the neonatal intensive care unit (aOR 2.25 [1.35, 3.75]). Women with Type 2 diabetes who missed an appointment were more likely to have a large-for-gestational-age infant (aOR 1.61 [1.13, 2.28]), and an extreme large-for-gestational-age infant (aOR 1.69 [1.02, 2.81]) compared with women who did not miss appointments. Above target HbA1c mediated the relationship between missed appointments and caesarean delivery in Type 1 diabetes and large-for-gestational age and extreme large-for-gestational age in Type 2 diabetes. CONCLUSION: In individuals with Type 1 and 2 diabetes, there are differences in neonatal outcomes between those who missed an appointment compared to those who did not. It remains unclear if missed diabetes appointments are causative or a marker of other health behaviours or risk factors leading to neonatal morbidity.

Maternal and neonatal outcomes in pregnancies with type 2 diabetes in First Nation and other Manitoban people: a population-based study.

BACKGROUND: First Nation people living in Canada experience a high prevalence of type 2 diabetes in pregnancy. In this study, we aimed to describe maternal and neonatal outcomes in First Nation and all other females with type 2 diabetes living in Manitoba, Canada. METHODS: This was a population-level retrospective cohort study using linked administrative data from Manitoba (2012-2017). We compared First Nation females with type 2 diabetes with all other Manitoban females with type 2 diabetes, using relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: A total of 2181 females with type 2 diabetes were included, and 1218 (55.8%) were First Nation. First Nation females with type 2 diabetes were significantly more likely to experience stillbirth (RR 2.14, 95% CI 1.11-4.13) and perinatal death (RR 2.39, 95% CI 1.37-4.17) than all other Manitoban females with type 2 diabetes. Offspring of First Nation females with type 2 diabetes had a higher risk of most neonatal complications than offspring of all other Manitoban females with type 2 diabetes, including a higher risk of congenital malformations (RR 1.97, 95% CI 1.30-2.99), but First Nation people did not have a higher risk of most maternal complications. INTERPRETATION: First Nation pregnant individuals living with type 2 diabetes experienced a higher risk for adverse pregnancy outcomes than all other Manitoban females with type 2 diabetes. Additional studies are needed to identify both high-risk and protective factors for pregnancy complications in First Nation people living with type 2 diabetes in pregnancy.

The association between gestational diabetes and stillbirth: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: Controversy exists over whether gestational diabetes increases the risk of stillbirth. The aim of this review was to examine the association between gestational diabetes and stillbirth. METHODS: We performed searches of the published literature to May 2021. Study selection and data extraction were performed in duplicate by independent reviewers. Meta-analyses of summary measures were conducted using random-effect models for cohort and case-control studies separately. The study protocol was registered in PROSPERO (registration ID CRD42020166939). RESULTS: From 9981 citations, 419 were identified for full-text review and 73 met inclusion criteria (n = 70,292,090). There was no significant association between gestational diabetes and stillbirth in cohort studies (pooled OR 1.04 [95% CI 0.90, 1.21]; I2 86.1%) or in case-control studies (pooled OR 1.57 [95% CI 0.83, 2.98]; I2 94.8%). Gestational diabetes was associated with lower odds of stillbirth among cohort studies presenting with an adjusted OR (pooled OR 0.78 [95% CI 0.68, 0.88]; I2 42.7%). Stratified analyses by stillbirth ≥28 weeks' gestation, studies published prior to 2013 and studies identified as low quality demonstrated a significantly higher odds of stillbirth in meta-regression (p = 0.016, 0.023 and 0.005, respectively). Egger's test for all included cohort studies (p = 0.018) suggests publication bias for the main meta-analysis. CONCLUSIONS/INTERPRETATION: Given the substantial heterogeneity across studies, there are insufficient data to define the relationship between stillbirth and gestational diabetes adequately. In the main analyes, gestational diabetes was not associated with an increased risk of stillbirth. However, heterogeneity across studies means this finding should be interpreted cautiously.

Metformin in Pregnancy for Women with Type 2 Diabetes: a Review.

PURPOSE OF REVIEW: To review the current evidence for the use of metformin in pregnancy for women with type 2 diabetes. RECENT FINDINGS: A large, multicenter, double-blind randomized controlled trial found that women with type 2 diabetes in pregnancy treated with metformin as an adjunct to insulin therapy had less gestational weight gain, insulin requirements, caesarian sections, macrosomia, and neonatal adiposity, but more neonates were small for gestational age (SGA) compared with insulin alone. It is unclear if the higher number of SGA infants are a direct result of metformin exposure or mediated through other effects such as less gestational weight gain and improved glycemic control. Additional follow-up studies of offspring exposed to metformin in utero are required. Metformin may be a useful adjunctive treatment for women with type 2 diabetes in pregnancy to help meet glycemic targets if there are no concerns for or indications of SGA.

An exploration of differences in infant feeding practices among women with and without diabetes in pregnancy: A mixed-methods study.

AIMS: (1) To determine the likelihood of full breastfeeding at 3 months postpartum in women with and without diabetes in pregnancy (DiP); (2) to explore the associations between diabetes management practices and infant feeding practices in those who had DiP and (3) to examine women's experiences of feeding their infants after having DiP. METHODS: The quantitative study used data from Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study. Participants who had DiP (n = 62) were matched 1:3 to participants without DiP for pre-pregnancy BMI, parity, mode of delivery and pre-term birth. Infant feeding questionnaires, prospective breastfeeding diaries and medical chart data were analysed to determine likelihood of fully breastfeeding at 3 months postpartum. For the qualitative study, interviews were conducted with postpartum women who had DiP to explore the experiences of infant feeding. Interviews were thematically analysed, and the results were compared between women who were categorized as 'full breast feeders' or 'mixed feeders'. RESULTS: The odds of fully breastfeeding were 50% lower in women with DiP than women without DiP (OR: 0.50, 95% CI 0.25-0.99, p = 0.04). Qualitative interviews identified that although all women showed resilience in the face of infant feeding challenges, those who were fully breastfeeding reported seeking out external infant feeding supports, for example, classes or Doula's. Mixed Feeders perceived there was a lack of infant feeding information and support given to them prior to giving birth. CONCLUSION: Women with DiP may require additional prenatal and postnatal infant feeding support to be better prepared to overcome feeding challenges they may face.

Novel Biochemical Markers of Glycemia to Predict Pregnancy Outcomes in Women With Type 1 Diabetes.

OBJECTIVE: The optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA1c, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes. RESEARCH DESIGN AND METHODS: One hundred fifty-seven women from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) were included in this prespecified secondary analysis. HbA1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5-anhydroglucitol, fructosamine, glycated albumin) were compared at ∼12, 24, and 34 weeks' gestation using logistic regression and receiver operating characteristic (ROC) curves to predict pregnancy complications (preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, admission to neonatal intensive care unit). RESULTS: HbA1c, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal outcomes at 24 weeks' gestation. More outcomes were associated with CGM metrics during the first trimester and with laboratory markers (area under the ROC curve generally <0.7) during the third trimester. Time in range (TIR) (63-140 mg/dL [3.5-7.8 mmol/L]) and time above range (TAR) (>140 mg/dL [>7.8 mmol/L]) were the most consistently predictive CGM metrics. HbA1c was also a consistent predictor of suboptimal pregnancy outcomes. Some alternative laboratory markers showed promise, but overall, they had lower predictive ability than HbA1c. CONCLUSIONS: HbA1c is still an important biomarker for obstetric and neonatal outcomes in type 1 diabetes pregnancy. Alternative biochemical markers of glycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared with widely available HbA1c and increasingly available CGM metrics (TIR and TAR).