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Baz Baz, Jean-Pierre Riveline, and Jean-François Gautier

Gestational diabetes (GDM) is defined as a glucose intolerance resulting in hyperglycaemia of variable severity with onset during pregnancy. This review aims to revisit the pathogenesis and aetiology of GDM in order to better understand its clinical presentation and outcomes. During normal pregnancy, insulin sensitivity declines with advancing gestation. These modifications are due to placental factors, progesterone and estrogen. In a physiological situation, a compensatory increase in insulin secretion maintains a normal glucose homeostasis. GDM occurs if pancreatic β-cells are unable to face the increased insulin demand during pregnancy. GDM is most commonly a forerunner of type 2 diabetes (T2D) – the most prevalent form of diabetes. These women share similar characteristics with predisposed subjects to T2D: insulin resistance before and after pregnancy, and carry more T2D risk alleles. Auto-immune and monogenic diabetes are more rare aetiologies of GDM. Adverse pregnancy outcomes of GDM are mainly related to macrosomia caused by fetal hyperinsulinism in response to high glucose levels coming from maternal hyperglycaemia. Screening recommendations and diagnosis criteria of GDM have been recently updated. High risk patients should be screened as early as possible using fasting plasma glucose, and if normal, at 24–28 weeks of gestation using 75 g oral glucose tolerance test. The treatment of GDM is based on education with trained nurses and dieticians, and if necessary insulin therapy.

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Blandine Tramunt, Sarra Smati, Sandrine Coudol, Matthieu Wargny, Matthieu Pichelin, Béatrice Guyomarch, Abdallah Al-Salameh, Coralie Amadou, Sara Barraud, Édith Bigot, Lyse Bordier, Sophie Borot, Muriel Bourgeon, Olivier Bourron, Sybil Charriere, Nicolas Chevalier, Emmanuel Cosson, Bruno Fève, Anna Flaus-Furmaniuk, Pierre Fontaine, Amandine Galioot, Céline Gonfroy-Leymarie, Bruno Guerci, Sandrine Lablanche, Jean-Daniel Lalau, Etienne Larger, Adele Lasbleiz, Bruno Laviolle, Michel Marre, Marion Munch, Louis Potier, Gaëtan Prévost, Eric Renard, Yves Reznik, Dominique Seret-begue, Paul Sibilia, Philippe Thuillier, Bruno Vergès, Jean-Francois Gautier, Samy Hadjadj, Bertrand Cariou, Franck Mauvais-Jarvis, and Pierre Gourdy

Objective:

Male sex is a determinant of severe coronavirus disease-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19.

Methods:

We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation [IMV], death, intensive care unit [ICU] admission and home discharge at day 7 [D7] or day 28 [D28]) in 2,380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736).

Results:

The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR 0.66 [0.49-0.88]), death (OR 0.49 [0.30-0.79]) and ICU admission (OR 0.57 [0.43-0.77]) at D7, but only with ICU admission (OR 0.58 [0.43-0.77]) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, CRP, AST and eGFR predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only.

Conclusions:

In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.