[Non-invasive glucose measurements : where do we stand?] / Mesures du glucose non invasives : où en est-on ?

The technologies used to measure blood glucose have significantly evolved the past few years, especially with the introduction of continuous interstitial glucose measurements, simplifying the management of the disease. More recently, there has been a lot of interest regarding some potential revolutionary methods, such as smartwatches, and glucose measurements in sweat, saliva, and even tears. In this article, we review the different technologies that are under development, and notice that although promising, they rest imprecise. False measurements can have fatal consequences for our patients. Nevertheless, these innovations are promising and have the potential to change the daily life of people with diabetes in the future.

Les technologies utilisées pour mesurer les glycémies des personnes présentant un diabète ont beaucoup évolué ces dernières années, avec notamment l'introduction des mesures interstitielles en continu, rendant le contrôle glycémique plus aisé. Depuis peu, il y a un intérêt croissant, notamment dans les médias, autour de potentielles méthodes révolutionnaires via des montres intelligentes, la sueur, la salive et même les larmes. Dans cet article, nous répertorions les différentes technologies en cours d'investigation et notons que plusieurs d'entre elles restent imprécises, empêchant leur utilisation pour nos patients diabétiques, chez qui des mesures incorrectes peuvent avoir de graves conséquences. Néanmoins, ces nouveautés sont prometteuses et ont le potentiel de changer le quotidien des personnes présentant un diabète dans le futur.

[The diabetic foot : a complex and multidisciplinary management]. / Pied diabétique : une prise en charge complexe et multidisciplinaire.

Diabetic foot syndrome is a common complication in people with diabetes and peripheral sensory impairment. This complex situation requires early clinical detection by various health care professionals, but also by patients and their relatives. The clinical course, the severity of the prognosis and the management will be determined by the speed of the diagnosis. In the case of confirmed disease, multidisciplinary management is necessary. The most important intervention, both for prevention and treatment, is the discharge of the affected foot.

Le syndrome du pied diabétique est une complication fréquente chez les personnes ayant un diabète et une atteinte de la sensibilité périphérique. Cette situation complexe nécessite une détection clinique précoce, par les divers professionnels de la santé mais aussi par les patients et leurs proches. L'évolution clinique, la gravité du pronostic et la prise en charge seront déterminées par la rapidité du diagnostic. En cas d'atteinte confirmée, une prise en charge multidisciplinaire est nécessaire. L'intervention la plus importante, tant pour la prévention que le traitement, est la décharge du pied atteint.

[Rapid and ultrarapid insulins: when and how?] / Insulines rapides et ultrarapides : quelles indications et utilités ?

Treatment combining long-acting and short-acting insulins is essential for people with type 1 diabetes, but may become also compulsory in other forms of diabetes in case of insulinopenia. The purpose of short-acting insulins is to mimic physiological insulin secretion in response to carbohydrate intake at meals. There is a delay between the injection and its action, sometimes limiting their use and effectiveness. Ultra-rapid insulins have been developed to more closely approximate the expected insulin response to a meal, through faster absorption. They do not improve diabetes control but allow more flexibility with mealtime injections. These new analogues are also an attractive alternative for use in insulin pumps.

Un traitement combinant insulines lente et rapide est essentiel pour les personnes avec un diabète de type 1, mais peut le devenir dans d'autres formes de diabète en cas d'insulinopénie. Le but des insulines rapides est de mimer la sécrétion physiologique d'insuline en réponse à la prise de glucides aux repas. Il y a un délai entre l'injection et son action, limitant parfois leur usage et leur efficacité. Des insulines ultrarapides ont été développées pour se rapprocher davantage de la réponse insulinique attendue à un repas, grâce à une absorption plus rapide. Elles n'améliorent pas le contrôle du diabète mais permettent plus de flexibilité avec les injections aux repas. Ces nouveaux analogues sont également une alternative intéressante pour une utilisation dans les pompes à insuline.

Efficacy of Ketogenic Diets on Type 2 Diabetes: a Systematic Review.

PURPOSE OF REVIEW: To assess the pleiotropic effects of ketogenic diets (KD) on glucose control, changes in medication, and weight loss in individuals with type 2 diabetes, and to evaluate its practical feasibility RECENT FINDINGS: KD results in improved HbA1c already after 3 weeks, and the effect seems to persist for at least 1 year. This is associated with a reduction in glucose-lowering medications. The weight loss observed after a short time period seems to be maintained with a long-term diet. Adequate support (supportive psychological counseling, enhancing positive affectivity, reinforcing mindful eating) is necessary to achieve a benefit and to assure adherence. Despite the documented decrease in HbA1, a definitive causal effect of KD remains to be proven. KD should be performed under strict medical supervision. Future research should clarify how compliance can be maximized and how ketosis can be optimally monitored.

Effect of nutrition on postprandial glucose control in hospitalized patients with type 2 diabetes receiving fully automated closed-loop insulin therapy.

Fully automated closed-loop insulin delivery may offer a novel way to manage diabetes in hospital. However, postprandial glycaemic control remains challenging. We aimed to assess the effect of nutritional intake on postprandial glucose control in hospitalized patients with type 2 diabetes receiving fully closed-loop insulin therapy. The effects of different meal types and macronutrient composition on sensor glucose time-in-target (TIT, 3.9-10.0 mmol/L) and mean sensor glucose were assessed with hierarchical linear models using a Bayesian estimation approach. TIT was lower and the mean sensor glucose slightly higher, after breakfast compared with lunch and dinner, whereas the insulin dose was higher. Across meals, when carbohydrates were replaced by fat, or to a lesser extent by protein, postprandial glucose control improved. For breakfast, a 3.9% improvement in TIT was observed when 10% of the energy from carbohydrates was replaced by fat. Improvements were slightly lower during lunch and dinner (3.2% and 3.4%) or when carbohydrates were replaced by protein (2.2 and 2.7%, respectively). We suggest that reducing carbohydrate at the expense of fat or protein, could further improve glucose control during fully closed-loop insulin therapy in hospital.

[New-onset diabetes and novel targeted therapies against cancer]. / Diabète secondaire aux nouvelles thérapies ciblées contre le cancer.

New systemic cancer therapies are increasingly oriented towards specific signaling pathways involved in carcinogenesis. However, these new treatments may lead to disorders of glycemic homeostasis ranging from glucose intolerance, diabetes or the occurrence of severe acute hyperglycemic syndrome due to blockade of certain pathways common to glucose metabolism. This article discusses the estimated frequency of new-onset diabetes, the pathophysiological mechanisms as well as the diagnostic, therapeutic, monitoring and prognostic management of glycemic dysfunction in patients treated with these novel systemic cancer therapies.

Les nouvelles thérapies du cancer sont de plus en plus orientées contre des voies de signalisation spécifiques à la carcinogenèse. Cependant, ces nouveaux traitements peuvent mener à des troubles de l'homéostasie glucidique, allant d'une intolérance au glucose au diabète insulinorequérant, avec une potentielle décompensation aiguë, en raison du blocage de certaines voies communes à l'homéostasie glucidique. Cet article discute de la fréquence estimée de la survenue du diabète, des mécanismes physiopathologiques ainsi que de la prise en charge diagnostique et thérapeutique, de la surveillance et du pronostic de la dysfonction glycémique chez les patients traités par ces nouvelles thérapies contre le cancer.

[Basal insulin therapy in patients with type 2 diabetes]. / Insulinothérapie basale chez les patients diabétiques de type 2.

Insulin therapy, often initiated after hygiene and dietary measures and non-insulin antidiabetics, is part of the treatment of patients with type 2 diabetes. Fear of injections or hypoglycemia often delays its implementation. However, its introduction is recommended in cases of poorly balanced diabetes despite a well-controlled therapeutic escalation but also in cases of acute imbalance. Introduction of insulin therapy requires patient education and close monitoring by the healthcare team. Type of insulin and its titration reduce the incidence of hypoglycemia in patients at risk. The determination of the fasting glycemic target - relative to HbA1c - for the titration of insulin is important to define for an optimal benefit (prevention of secondary complications)/risk (hypoglycemia, weight gain) balance.

L'insulinothérapie, souvent mise en place après les mesures hygiéno-diététiques et les antidiabétiques non insuliniques, fait partie du traitement des patients diabétiques de type 2. La peur des injections ou des hypoglycémies retarde souvent sa mise en place. Cependant, son introduction est recommandée en cas de diabète mal équilibré malgré une escalade thérapeutique bien conduite mais aussi en cas de déséquilibre aigu. L'insulinothérapie implique un enseignement au patient et un suivi rapproché par l'équipe soignante. Le type d'insuline et sa titration progressive permettent de réduire l'incidence des hypoglycémies chez les patients à risque. La détermination de la cible glycémique pour la titration de l'insuline est importante à définir pour une balance bénéfice (prévention des complications secondaires)/risque (hypoglycémie, prise pondérale) optimale.

[Practical considerations in the use of SGLT2 inhibitors in cardiovascular diseases]. / Considérations pratiques pour l'utilisation des inhibiteurs du SGLT2 dans les maladies cardiovasculaires.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of drugs which offer cardiovascular (CV) and renal benefits. They are currently indicated as first-line treatments of type 2 diabetes mellitus (T2DM) in patients with CV disease, high CV risk, renal disease, or heart failure with reduced ejection fraction (HFrEF). Two randomized clinical trials have shown the benefits of dapagliflozin and empagliflozin in patients with HFrEF, regardless of the presence of T2DM. Despite an overall favorable safety profile, attention has to be paid to adverse events, such as an increased risk of euglycemic diabetic ketoacidosis and genital mycotic infections. We present an up-to-date narrative literature review of the physiological mechanisms of action, current indications, and side effects of SGLT2 inhibitors.

Les inhibiteurs du cotransporteur sodium-glucose de type 2 (iSGLT2) sont une classe d'antidiabétiques oraux ayant de nombreux bénéfices cardiovasculaires (CV) et rénaux. Ils sont indiqués chez les patients avec un diabète de type 2 (DT2) et une maladie CV, un risque CV élevé, une insuffisance rénale chronique ou une insuffisance cardiaque à fraction d'éjection réduite (ICFER). Des essais cliniques randomisés ont montré les bénéfices de la dapagliflozine et de l'empagliflozine chez les patients avec une ICFER, avec ou sans DT2. Malgré un profil de sécurité favorable, il convient de connaître les effets indésirables éventuels, tels que l'acidocétose euglycémique et les infections génito-urinaires. Nous présentons une revue narrative de la littérature à jour portant sur les mécanismes d'action, indications et effets secondaires des iSGLT2.

[Diabetes and COVID-19 infection]. / Diabète et infection à COVID-19.

Based on the epidemiological data currently available, diabetes does not seem to be a risk factor for infection with SARS-CoV-2 but may be associated with a more severe course. Diabetes is extremely common in older patients with co-morbidities who are at risk of unfavorable outcomes. As with any other infection, poorly controlled pre-existing diabetes can promote secondary infections and lead to acute complications related to hyperglycemia, worsened itself by the infection. It is important to advise patients to have enough diabetic equipment and supplies at home, to make regular blood glucose self-tests, and to contact a caregiver immediately in case of glycemic imbalance or signs of infection. Antidiabetic therapy may need adjustments following usual sick day rules. Insulin therapy should be considered to treat any persistent hyperglycemia in patients hospitalized for an acute infection.

D'après les données épidémiologiques actuellement disponibles, le diabète ne semble pas être un facteur de risque d'infection par le SARS-CoV-2. Il est cependant associé à une maladie plus sévère principalement en raison de sa haute prévalence chez les personnes âgées et polymorbides dont l'évolution est plus souvent défavorable. Comme lors de n'importe quelle autre infection, un diabète préexistant, surtout s'il est mal contrôlé, peut favoriser les surinfections et entraîner des complications aiguës liées à l'hyperglycémie, elle-même majorée par l'infection. Il est important de recommander aux patients d'avoir suffisamment de matériel à domicile, d'effectuer des automesures régulières de la glycémie, ainsi que de contacter un soignant immédiatement en cas de déséquilibre glycémique ou d'infection. Le traitement antidiabétique doit être adapté comme habituellement en cas d'infection. Une insulinothérapie doit être envisagée en cas d'hyperglycémie persistante chez tout patient hospitalisé pour une infection aiguë.

Combined immune checkpoint inhibitor therapy with nivolumab and ipilimumab causing acute-onset type 1 diabetes mellitus following a single administration: two case reports.

BACKGROUND: The use of immune checkpoint inhibitor (ICI) therapy is becoming a standard of care for several cancers. Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) or its ligand (PD-L1) cause a broad spectrum of autoimmune adverse events. ICI-induced type 1 diabetes mellitus (T1DM) is extremely rare (< 1%) but potentially life-threatening. It appears to be more common with PD-1 blockade (or combination immunotherapy) than with anti-CTLA-4 therapy, often during the first three to six months of therapy. CASES PRESENTATION: We report an acute onset T1DM with severe inaugural diabetic ketoacidosis (DKA) and remarkably elevated Glutamic Acid Decarboxylase antibody (GADA) titres following a single administration of combined ICI therapy with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) in two adult patients with advanced metastatic melanoma. In these cases, the time to diabetes onset was remarkably short (two and five weeks), and one presented with fulminous T1DM in a previous long-standing type 2 diabetes mellitus. CONCLUSIONS: Oncological patients treated with combination therapy of anti-PD-1 and anti-CTLA-4 can develop a particular pattern of T1DM, with very rapid onset within a few weeks after starting ICI therapy, even in the presence of an existing type 2 diabetes. ICI-induced T1DM is a medical emergency in presence of severe inaugural DKA and requires a collaboration between specialists and primary care physicians, as well as patient education, for early diagnosis and supportive care.

[Statin-associated muscle symptoms : Current management in 2018]. / Symptômes musculaires associés aux statines : quelle prise en charge en 2018 ?

Statins are the first line treatment in hyperlipidemia, either in primary or secondary prevention of cardiovascular diseases. One of the most prescribed drug class worldwide, this drug class is often the focus of highly publicized drug controversies. Various adverse effects have been attributed to statins, in particular statin-associated muscle symptoms (SAMS). This condition varies in severity (from frequent isolated myalgia to rare severe myositis, even rhabdomyolysis) and often leads to treatment termination. Because SAMS are a daily challenge in clinical practice, we review here the recent medical literature on this topic and suggest a management strategy to be shared with the patient as an active partner.

Les statines représentent la première ligne de traitement en cas d'hypercholestérolémie, que ce soit en prévention primaire ou secondaire des maladies cardiovasculaires. C'est l'une des classes médicamenteuses les plus prescrites au monde, mais qui fait l'objet de controverses médiatisées. De nombreux effets indésirables ont été attribués à la prise de statines, notamment les symptômes musculaires associés aux statines (SMAS). On relève différents types d'atteinte, d'intensité croissante (de myalgies fréquentes à une myosite sévère mais rare, voire une rhabdomyolyse), pouvant mener à l'arrêt du traitement. Au vu du défi que représentent les SMAS dans la pratique courante ambulatoire, cet article donne au praticien un aperçu de la littérature récente, ainsi qu'une proposition de prise en charge à partager avec le patient.

[Type 1 diabetes, physical activity and novel technology]. / Diabète de type 1, activité physique et nouvelles technologies.

Physical activity is recommended for all patients with diabetes, but it is important to be particularly attentive in patients with type 1 diabetes. Because of their treatment, these patients have a higher risk of hypoglycemia. The challenge for both caregivers and the patient is to find the best possible strategy to practice the desired physical activity without any significant hypo- or hyperglycemia. Thus, an adaptation of the insulin and/or nutritional treatment is necessary, depending on the type, intensity and duration of the physical activity. Moreover, many technological devices are now available that can improve patient care, but they also have some limitations to take into account. Allover, an interdisciplinary approach is highly recommended, both for a specific or a regular physical activity practice.

L'activité physique est recommandée pour tous les patients avec un diabète, mais une attention particulière est nécessaire en cas de diabète de type 1. En effet, ces patients sont à haut risque d'hypoglycémie. Le défi des soignants et du patient est donc de trouver la meilleure stratégie possible pour pouvoir pratiquer l'activité physique souhaitée, et cela sans faire d'hypo ou d'hyperglycémie. Une adaptation du traitement d'insuline et/ou de l'alimentation est nécessaire, en fonction du type, de l'intensité et de la durée de l'activité physique. Il existe désormais plusieurs outils technologiques permettant d'améliorer la prise en charge du patient, lesquels ont également des limitations. Ainsi, une prise en charge interdisciplinaire diabétologique est recommandée en vue de la pratique d'une activité physique régulière ou ponctuelle.

[Ketogenic diets : the miraculous solution ?] / Diètes cétogènes : la solution miracle ?

The treatment of obesity and cardiovascular diseases is one of the most difficult and important challenges nowadays. Weight loss is frequently offered and aimed at improving some of the components of the metabolic syndrome. Among various diets, carbohydrate restriction is popular, specifically ketogenic diets, which are very low in carbohydrates and usually high in fats and /or proteins. Results are controversial, but some benefits such as weight loss and improved glycemic control have been described. Nevertheless, these effects seem to be limited in time. Moreover, these diets are not totally safe and can be associated with some adverse events such as the development of nonalcoholic fatty liver disease. The aim of this review is to discuss the role of ketogenic diets on different cardiovascular risk factors based on available evidence.

La prise en charge de l'obésité et des maladies cardiovasculaires est l'un des plus difficiles et importants défis. Perdre du poids est fréquemment proposé afin d'améliorer les différents composants du syndrome métabolique. Parmi les nombreux régimes existants, la limitation en glucides est populaire, notamment les diètes cétogènes. Ces dernières sont pauvres en hydrates de carbone et souvent riches en graisses et/ou protéines. Leurs effets sont controversés, mais certains bénéfices tels que perte de poids et amélioration glucométabolique sont décrits. Cependant, ces effets semblent limités dans le temps. Ces régimes ne sont pas dépourvus d'effets secondaires et pourraient même favoriser le développement d'une stéatose hépatique. Nous allons donc passer en revue l'impact de ces diètes sur les différents facteurs de risque cardiovasculaire.

Effects of empagliflozin on reproductive system in men without diabetes.

Sodium-glucose cotransporter (SGLT) 2 inhibition is a well-known target for the treatment of type 2 diabetes, renal disease and chronic heart failure. The protein SGLT2 is encoded by SLC5A2 (Solute Carrier Family 5 Member 2), which is highly expressed in renal cortex, but also in the testes where glucose uptake may be essential for spermatogenesis and androgen synthesis. We postulated that in healthy males, SGLT2 inhibitor therapy may affect gonadal function. We examined the impact on gonadal and steroid hormones in a post-hoc analysis of a double-blind, randomized, placebo-controlled research including 26 healthy males who were given either placebo or empagliflozin 10 mg once daily for four weeks. After one month of empagliflozin, there were no discernible changes in androgen, pituitary gonadotropin hormones, or inhibin B. Regardless of BMI category, the administration of empagliflozin, a highly selective SGLT2 inhibitor, did not alter serum androgen levels in men without diabetes. While SGLT2 is present in the testes, its inhibition does not seem to affect testosterone production in Leydig cells nor inhibin B secretion by the Sertoli cells.

Effects of Aerobic Exercise on Systemic Insulin Degludec Concentrations in People with Type 1 Diabetes.

BACKGROUND: There is conflicting evidence on the effect of exercise on systemic insulin concentrations in adults with type 1 diabetes. METHODS: This prospective single-arm study examined the effect of exercise on systemic insulin degludec (IDeg) concentrations. The study involved 15 male adults with type 1 diabetes (age 30.7 ± 8.0 years, HbA1c 6.9 ± 0.7%) on stable IDeg regimen. Blood samples were collected every 15 minutes at rest, during 60 minutes of cycling (66% VO2max) and until 90 minutes after exercise termination. IDeg concentrations were quantified using high-resolution mass-spectrometry and analyzed applying generalized estimation equations. RESULTS: Compared to baseline, systemic IDeg increased during exercise over time (P < .001), with the highest concentrations observed toward the end of the 60-minute exercise (17.9% and 17.6% above baseline after 45 minutes and 60 minutes, respectively). IDeg levels remained elevated until the end of the experiment (14% above baseline at 90 minutes after exercise termination, P < .001). CONCLUSIONS: A single bout of aerobic exercise increases systemic IDeg exposure in adults on a stable basal IDeg regimen. This finding may have important implications for future hypoglycemia mitigation strategies around physical exercise in IDeg-treated patients.

Impact of Risk Factors on Short and Long-Term Maternal and Neonatal Outcomes in Women With Gestational Diabetes Mellitus: A Prospective Longitudinal Cohort Study.

Aims: Universal screening of gestational diabetes mellitus (GDM) in women with no risk factors (RF) for GDM remains controversial. This study identified the impact of the presence of RF on perinatal and postpartum outcomes. Methods: This prospective cohort study included 780 women with GDM. GDM RF included previous GDM, first grade family history of type 2 diabetes, high-risk ethnicity and pre-pregnancy overweight/obesity (OW/OB). Outcomes included obstetrical, neonatal and maternal metabolic parameters during pregnancy and up to 1 year postpartum. Results: Out of 780 patients, 24% had no RF for GDM. Despite this, 40% of them needed medical treatment and they had a high prevalence of glucose intolerance of 21 and 27% at 6-8 weeks and 1-year postpartum, respectively. Despite similar treatment, women with RF had more neonatal and obstetrical complications, but they had especially more frequent adverse metabolic outcomes in the short- and long-term. The most important RF for poor perinatal outcome were previous GDM and pre-pregnancy OW/OB, whereas high-risk ethnicity and pre-pregnancy OW/OB were RF for adverse postpartum metabolic outcomes. Increasing number of RF were associated with worsened perinatal and long-term postpartum outcomes except for pregnancy-induced hypertension, C-section delivery and neonatal hypoglycaemia. Conclusion: Women with no RF had a high prevalence of adverse perinatal and postpartum outcomes, while the presence of RF particularly increased the risk for postpartum adverse metabolic outcomes. This calls for a RF-based long-term follow-up of women with GDM.

Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on ß-Cell Function at 1 Year After Surgery: A Systematic Review.

Bariatric surgery is a highly effective obesity treatment resulting in substantial weight loss and improved glucose metabolism. We hereby aimed to summarize available evidence of the effect of the 2 most common bariatric surgery procedures, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), on dynamic measures of ß-cell function (BCF). A systematic search of the literature was conducted in 3 bibliographic databases for studies reporting effects of RYGB and/or SG on BCF assessed using dynamic metabolic perturbation (oral or intravenous bolus stimulation), performed before and 1 year (±3 months) after surgery. Twenty-seven unique studies (6 randomized controlled trials and 21 observational studies), involving a total of 1856 obese adults, were included for final analysis. Twenty-five and 9 studies report effects of RYGB and SG on BCF, respectively (7 studies compared the 2 procedures). Seven studies report results according to presurgical diabetes status. Owing to variable testing procedures and BCF indices reported, no meta-analysis was feasible, and data were summarized qualitatively. For both surgical procedures, most studies suggest an increase in BCF and disposition index, particularly when using oral stimulation, with a more pronounced increase in diabetic than nondiabetic individuals. Additionally, limited indications for greater effects after RYGB versus SG were found. The quality of the included studies was, in general, satisfactory. The considerable heterogeneity of test protocols and outcome measures underscore the need for a harmonization of BCF testing in future research.

Cardio-Metabolic and Mental Health Outcomes Before and During the COVID-19 Pandemic in a Cohort of Women With Gestational Diabetes Mellitus in Switzerland.

Background: The COVID-19 pandemic has been associated with worsened metabolic and mental health in the general and perinatal population. The postpartum is a critical moment regarding these outcomes particularly in women with gestational diabetes mellitus (GDM). We investigated the cardio-metabolic and mental health outcomes before and during the pandemic in this population. Methods: This cohort study included 418 women with GDM, recruited during two distinct periods. This included 180 women exposed to the pandemic (E+) and recruited between May 2020-April 2021 and 238 women who were not exposed to the pandemic during their postpartum period (attended a year before=non-exposed (E-)) and recruited between January-December 2019. Among the E+, a nested-subcohort of 120 women were exposed both during pregnancy and postpartum. During the pandemic, we adopted a hybrid follow-up of women that consisted of in-person consultations, regular contact via phone calls (35%), sent recorded exercise guide to patients to follow at home and linked to our website. We specifically focused on maintaining motivation and keeping a strong focus on healthy lifestyle behaviors. Obstetric, neonatal, cardio-metabolic and mental health outcomes were assessed during pregnancy and postpartum. Results: The pandemic was not associated with worsened weight, weight retention, glucose tolerance, metabolic syndrome, well-being or depression in the postpartum with the exception of a minimally increased HbA1c, diastolic blood pressure and lower emotional eating scores in E+ women (all p ≤ 0.046). In the nested subcohort, E+ women had a slightly increased HbA1c at the first GDM visit and a higher need for glucose-lowering medication (both p ≤ 0.014), but HbA1c at the end of pregnancy and other cardio-metabolic, mental health, obstetric and neonatal outcomes during pregnancy were similar. Conclusions: The pandemic was not associated with any clinically relevant worsening of cardio-metabolic, mental health, obstetrical and neonatal outcomes in our GDM cohort. This was possibly due to a continued hybrid follow-up, and the partial lockdown in Switzerland.

Adverse metabolic outcomes in the early and late postpartum after gestational diabetes are broader than glucose control.

INTRODUCTION: Gestational diabetes mellitus is associated with an increased cardiovascular risk. To better target preventive measures, we performed an in-depth characterization of cardiometabolic risk factors in a cohort of women with gestational diabetes in the early (6-8 weeks) and late (1 year) postpartum. RESEARCH DESIGN AND METHODS: Prospective cohort of 622 women followed in a university gestational diabetes clinic between 2011 and 2017. 162 patients who attended the late postpartum visit were analyzed in a nested long-term cohort starting in 2015. Metabolic syndrome (MetS) was based on the International Diabetes Federation definition, and then having at least two additional criteria of the MetS (blood pressure, triglycerides, high-density lipoprotein (HDL) cholesterol, plasma glucose above or below the International Diabetes Federation cut-offs). RESULTS: Compared with prepregnancy, weight retention was 4.8±6.0 kg in the early postpartum, and the prevalence of obesity, pre-diabetes, MetS-body mass index (BMI) and MetS-waist circumference (WC) were 28.8%, 28.9%, 10.3% and 23.8%, respectively. Compared with the early postpartum, weight did not change and waist circumference decreased by 2.6±0.6 cm in the late postpartum. However, the prevalence of obesity, pre-diabetes, MetS-WC and MetS-BMI increased (relative increase: 11% for obesity, 82% for pre-diabetes, 50% for MetS-WC, 100% for MetS-BMI; all p≤0.001).Predictors for obesity were the use of glucose-lowering treatment during pregnancy and the prepregnancy BMI. Predictors for pre-diabetes were the early postpartum fasting glucose value and family history of diabetes. Finally, systolic blood pressure in pregnancy and in the early postpartum, the 2-hour post oral glucose tolerance test glycemia and the HDL-cholesterol predicted the development of MetS (all p<0.05). CONCLUSIONS: The prevalence of metabolic complications increased in the late postpartum, mainly due to an increase in fasting glucose and obesity, although weight did not change. We identified predictors of late postpartum obesity, pre-diabetes and MetS that could lead to high-risk identification and targeted preventions.

Exposure to alirocumab during the first trimester of pregnancy: A case report.

BACKGROUND: Familial hypercholesterolemia can be efficiently treated with combined lipid-lowering drugs. Lipid-lowering drugs are usually withdrawn for pregnancy and breastfeeding, ideally preconception, followed by lipid apheresis, however, careful plans can be precipitated due to unexpected pregnancy. CASE: A 28-year old woman with familial hypercholesterolemia due to heterozygous LDLR mutations had an LDL-cholesterol level at 14.6 mmol/L and Lp(a) at 1150 mg/L. She required a three-vessel coronary artery bypass graft, drug-eluting stents, rosuvastatin, ezetimibe, and alirocumab at maximal dosage. Contraception was advised during the following 12 months, with a planned drug withdrawal to bridge with lipid apheresis, such as the direct adsorption of lipoproteins (DALI). However, an unplanned pregnancy required an abrupt stop of all oral medications at six gestational weeks, except for aspirin. Lipid apheresis controlled LDL-cholesterol in the range of 4.9-7.9 mmol/L (before DALI session) to 1.2-3.2 mmol/L (after DALI session). Later, the regular pregnancy ultrasounds highlighted an isolated agenesis of the corpus callosum later confirmed by magnetic resonance imaging. CONCLUSIONS: A causal link between the early pregnancy exposure to PCSK9 inhibitors (or statins and ezetimibe taken concomitantly) and the observed complete agenesis of the corpus callosum seems unlikely in this case. Guidelines do not specifically recommend preconception measures to lower fetal and/or maternal risks of patients with severe FH considering pregnancy. We argue that lipid apheresis and other measures should be discussed with women with FH and maternity project on an individual basis, until pharmacoepidemiology studies assessing the safety of PCSK9 inhibitors in pregnancy are available.