Patients with coronavirus disease 2019 (COVID-19) are reported to have a greater prevalence of hyperglycaemia. Cytokine release as a consequence of severe acute respiratory syndrome coronavirus 2 infection may precipitate the onset of metabolic alterations by affecting glucose homeostasis. Here we describe abnormalities in glycometabolic control, insulin resistance and beta cell function in patients with COVID-19 without any pre-existing history or diagnosis of diabetes, and document glycaemic abnormalities in recovered patients 2 months after onset of disease. In a cohort of 551 patients hospitalized for COVID-19 in Italy, we found that 46% of patients were hyperglycaemic, whereas 27% were normoglycaemic. Using clinical assays and continuous glucose monitoring in a subset of patients, we detected altered glycometabolic control, with insulin resistance and an abnormal cytokine profile, even in normoglycaemic patients. Glycaemic abnormalities can be detected for at least 2 months in patients who recovered from COVID-19. Our data demonstrate that COVID-19 is associated with aberrant glycometabolic control, which can persist even after recovery, suggesting that further investigation of metabolic abnormalities in the context of long COVID is warranted.

The relationship between in utero fetal growth and fetal leptin concentrations was investigated between 19 and 41 wk in 40 normal (appropriate for gestational age, AGA) fetuses, in 25 intrauterine growth-restricted (IUGR) fetuses, and in 18 fetuses from gestational diabetic mothers (GDM), representing different intrauterine growth patterns. Umbilical venous plasma leptin concentrations were determined at the time of either in utero fetal blood sampling or delivery. Plasma leptin was measurable as early as 19 wk of gestation. A significant difference was observed between umbilical venous and arterial plasma leptin concentrations (0.6 Ϯ 0.6 ng/mL; p Ͻ 0.01). In AGA and in IUGR fetuses, significant positive relationships were found between fetal leptin concentrations and both gestational age (p Ͻ 0.001) and fetal weight (p Ͻ 0.001). Leptin concentrations were significantly higher in AGA than IUGR only after 34 wk (p Ͻ 0.05), but leptin per kilogram fetal weight (leptin/kg) was not significantly different. In IUGR with abnormal umbilical arterial Doppler velocimetry and fetal heart rate, leptin/kg significantly higher than in IUGR with normal biophysical and biochemical parameters was found (p Ͻ 0.05). Both circulating plasma leptin and leptin/kg were significantly higher in GDM than in normal fetuses (p Ͻ 0.001) and correlated with abdominal fat mass measured by ultrasound. No gender differences were observed in any group of fetuses. These findings indicate a clear relationship between fetal leptin concentrations and fetal fat mass. Data in severe IUGR suggest the presence of increased leptin concentrations associated with in utero signs of fetal distress. Abbreviations AGA, appropriate for gestational age IUGR, intrauterine growth restricted LGA, large for gestational age GDM, gestational diabetes mellitus PI, pulsatility index FHR, fetal heart rate FBS, fetal blood sampling Leptin is a circulating polypeptide hormone expressed abundantly in the adipose tissue (1) that regulates body weight and energy expenditure through a negative feedback signal between the adipose tissue and the hypothalamic centers of satiety (2). In humans, there is a positive correlation between leptin and body fat content or body mass index (BMI), with a sexual dimorphism in its regulation at the same level of fatness or BMI, and significantly higher concentrations in females than in males (3, 4). Moreover, leptin deficiency is accompanied by reduced fertility in ob/ob female mice and leptin treatment restored fertility along with decreased dietary intake, body weight, and fat mass (5). Recently, these data have been confirmed in a 9-y-old girl with congenital leptin deficiency treated with recombinant leptin that lead to a sustained reduction in body weight and percent body fat, which was associated with an increase in gonadotropin concentrations and pulsatility (6).Leptin concentrations have been measured in cord blood of newborn infants and a significant relationship has been reported with fetal weight (7-11). Both fetal and placental pr...

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Background: Ghrelin exerts a wide range of metabolic functions. In contrast to the body of information accumulated on the role of ghrelin on energy balance, the possible relevance of the peptide on GH secretion in physiological and pathological conditions has so far been poorly investigated. Aim: The aim of the present study was to evaluate circulating ghrelin levels in acromegalic patients in basal conditions and in response to oral glucose tolerance test (OGTT). Patients: Serum ghrelin, insulin and leptin levels were measured in 31 healthy normal weight subjects as controls, 25 patients with simple obesity and 17 non-diabetic acromegalic patients. Ghrelin and insulin response to OGTT was evaluated in six controls, four obese and six acromegalic patients. Results: The acromegalic patients showed ghrelin levels lower than those observed in normal weight subjects (201^20 vs 329^32 pmol=l; P , 0:05) and similar to those found in obese subjects (165^14 pmol=l; P ¼ not significant). Both obese and acromegalic patients had insulin levels significantly higher than controls, while high levels of leptin were detected only in obese subjects. Serum ghrelin levels showed a significant negative correlation with insulin, leptin and body mass index ðP , 0:05Þ in normal and obese subjects. No correlation was observed in acromegalic patients, although those with severe insulin resistance showed the lowest ghrelin values ð161^20 pmol=lÞ: In controls and obese subjects, ghrelin levels showed a significant decrease (25 -40%) during OGTT, while no effect was detectable in acromegalic patients. Conclusions: This study reports that patients with active acromegaly show low levels of circulating ghrelin that are not further reduced by OGTT, this pattern of secretion probably depending on both GH-induced insulin resistance and the putative GH/IGF-I negative feedback control on ghrelin secretion.

Objective: Ghrelin is a GH secretagog isolated recently from rat stomach and involved in the stimulation of food intake and adiposity in rodents and humans. Moreover, subsequent studies showed that ghrelin is expressed in rat and human placenta, suggesting a possible influence of the peptide on fetal growth. The aim of this study was to evaluate circulating levels of ghrelin in appropriate for gestational age (AGA) or intrauterine growth-restricted (IUGR) fetuses. Subjects and methods: Ghrelin levels between 20 and 39 weeks of gestation were measured in 16 AGA and nine IUGR fetuses in whom blood was collected by cordocentesis performed for prenatal diagnosis of different diseases or during elective cesarean section. In most samples, GH, cortisol and leptin levels were also evaluated. Results are expressed as means^S.D. Differences were tested using the Student's t-test with Welch correction. P , 0.05 was considered significant. Results: All fetuses showed levels of ghrelin in the umbilical venous blood (100^99 pmol/l) that did not correlate with the gestational age or the maternal ghrelin levels. No difference was found between umbilical venous and arterial concentrations, suggesting that fetal tissues are a source of ghrelin. Ghrelin levels in IUGR fetuses were significantly higher than those found in AGA fetuses (176^125 vs 58^44 pmol/l; P , 0.005). Moreover, in samples obtained at birth, ghrelin concentrations correlated negatively with birth weight (P , 0.05). In IUGR fetuses, GH and cortisol concentrations were higher and leptin levels lower than in AGA fetuses, although no significant correlation between these parameters and ghrelin levels was found. Conclusion: The presence of ghrelin in the fetal circulation as well as its increase in IUGR fetuses suggest a role of this peptide during intrauterine development.

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Cortisol excess did not directly affect ghrelin and ApN levels in patients with CD. The observation that ghrelin levels were low during the active phase of CD and increased after recovery suggests that glucocorticoids may influence ghrelin levels indirectly by modulating adiposity and metabolic signals over the long term.

OSAS is associated with reduced levels of adiponectin independently of insulin-resistance and BMI. These low adiponectin levels may contribute to the increased mortality seen in such patients.