Farming activity and risk of treated thyroid disorders: Insights from the TRACTOR project, a nationwide cohort study.

BACKGROUND: Epidemiological data regarding thyroid diseases are lacking, in particular for occupationally exposed populations. OBJECTIVES: To compare the risk of hypothyroidism and hyperthyroidism between farming activities within the complete population of French farm managers (FMs). METHODS: Digital health data from retrospective administrative databases, including insurance claims and electronic health/medical records, was employed. This cohort data spanned the entirety of French farm managers (FMs) who had undertaken work at least once from 2002 to 2016. Survival analysis with the time to initial medication reimbursement as timescale was used to examine the association (hazard ratio, HR) between 26 specific farming activities and both treated hypothyroidism and hyperthyroidism. A distinct model was developed for each farming activity, comparing FMs who had never engaged in the specific farming activity between 2002 and 2016 with those who had. All analyses were adjusted for potential confounders (e.g., age), and sensitivity analyses were conducted. RESULTS: Among 1088561 FMs (mean age 46.6 [SD 14.1]; 31% females), there were 31834 hypothyroidism cases (75% females) and 620 hyperthyroidism cases (67% females), respectively. The highest risks were observed for cattle activities for both hyperthyroidism (HR ranging from 1.75 to 2.42) and hypothyroidism (HR ranging from 1.41 to 1.44). For hypothyroidism, higher risks were also observed for several animal farming activities (pig, poultry, and rabbit), as well as fruit arboriculture (HR = 1.22 [1.14-1.31]). The lowest risks were observed for activities involving horses. Sex differences in the risk of hypothyroidism were observed for eight activities, with the risk being higher for males (HR = 1.09 [1.01-1.20]) than females in viticulture (HR = 0.97 [0.93-1.00]). The risk of hyperthyroidism was two times higher for male dairy farmers than females. DISCUSSION: Our findings offer a comprehensive overview of thyroid disease risks within the FM community. Thyroid ailments might not stem from a single cause but likely arise from the combined effects of various causal agents and triggering factors (agricultural exposome). Further investigation into distinct farming activities-especially those involving cattle-is essential to pinpoint potential risk factors that could enhance thyroid disease monitoring in agriculture.

Perigestational exposure of a combination of a high-fat diet and pesticide impacts the metabolic and microbiotic status of dams and pups; a preventive strategy based on prebiotics.

PURPOSE: Metabolic changes during the perinatal period are known to promote obesity and type-2 diabetes in adulthood via perturbation of the microbiota. The risk factors for metabolic disorders include a high-fat diet (HFD) and exposure to pesticide residues. The objective of the present study was to evaluate the effects of perigestational exposure to a HFD and chlorpyrifos (CPF) on glycemia, lipid profiles, and microbial populations in Wistar dams and their female offspring. We also tested a preventive strategy based on treatment with the prebiotic inulin. METHODS: From 4 months before gestation to the end of the lactation period, six groups of dams were exposed to either a standard diet, a HFD alone, CPF alone, a combination of a HFD and CPF, and/or inulin supplementation. All female offspring were fed a standard diet from weaning to adulthood. We measured the impacts of these exposures on glycemia, the lipid profile, and the microbiota (composition, metabolite production, and translocation into tissues). RESULTS: HFD exposure and CPF + HFD co-exposure induced dysmetabolism and an imbalance in the gut flora in both the dams and the female offspring. Inulin mitigated the impact of exposure to a HFD alone but not that of CPF + HFD co-exposure. CONCLUSION: Our results provide a better understanding of the complex interactions between environmental pollutants and diet in early life, including in the context of metabolic diseases.

The association between body mass index class and coronavirus disease 2019 outcomes.

BACKGROUND/OBJECTIVES: A growing body of data suggests that obesity influences coronavirus disease 2019 (COVID-19). Our study's primary objective was to assess the association between body mass index (BMI) categories and critical forms of COVID-19. SUBJECTS/METHODS: Data on consecutive adult patients hospitalized with laboratory-confirmed COVID-19 at Amiens University Hospital (Amiens, France) were extracted retrospectively. The association between BMI categories and the composite primary endpoint (admission to the intensive care unit or death) was probed in a logistic regression analysis. RESULTS: In total, 433 patients were included, and BMI data were available for 329: 20 were underweight (6.1%), 95 have a normal weight (28.9%), 90 were overweight (27.4%), and 124 were obese (37.7%). The BMI category was associated with the primary endpoint in the fully adjusted model; the odds ratio (OR) [95% confidence interval (CI)] for overweight and obesity were respectively 1.58 [0.77-3.24] and 2.58 [1.28-5.31]. The ORs [95% CI] for ICU admission were similar for overweight (3.16 [1.29-8.06]) and obesity (3.05 [1.25-7.82]) in the fully adjusted model. The unadjusted ORs for death were similar in all BMI categories while obesity only was associated with higher risk after adjustment. CONCLUSIONS: Our results suggest that overweight (and not only obesity) is associated with ICU admission, but overweight is not associated with death.

Characteristics and outcomes of COVID-19 in hospitalized patients with and without diabetes.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic, with four million confirmed cases and 280 000 deaths at the time of writing. Some studies have suggested that diabetes is associated with a greater risk of developing severe forms of COVID-19. The primary objective of the present study was to compare the clinical features and outcomes in hospitalized COVID-19 patients with vs without diabetes. METHODS: All consecutive adult patients admitted to Amiens University Hospital (Amiens, France) with confirmed COVID-19 up until April 21st, 2020, were included. The composite primary endpoint comprised admission to the intensive care unit (ICU) and death. Both components were also analysed separately in a logistic regression analysis and a Cox proportional hazards model. RESULTS: A total of 433 patients (median age: 72; 238 (55%) men; diabetes: 115 (26.6%)) were included. Most of the deaths occurred in non-ICU units and among older adults. Multivariate analyses showed that diabetes was associated neither with the primary endpoint (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.66-1.90) nor with mortality (hazard ratio: 0.73; 95%CI: 0.40-1.34) but was associated with ICU admission (OR: 2.06; 95%CI 1.09-3.92, P = .027) and a longer length of hospital stay. Age was negatively associated with ICU admission and positively associated with death. CONCLUSIONS: Diabetes was prevalent in a quarter of the patients hospitalized with COVID-19; it was associated with a greater risk of ICU admission but not with a significant elevation in mortality. Further investigation of the relationship between COVID-19 severity and diabetes is warranted.

Correction to: Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study.

The authors regret a mistake in Table 1.

Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study.

AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736.

Congenital and acquired hypothyroidism: temporal and spatial trends in France from 2014 to 2019.

PURPOSE: To assess the incidence of congenital hypothyroidism (CH) and acquired hypothyroidism (AH) between 2014 and 2019 in continental France. METHODS: New cases of CH and AH were identified using the French National Health Data System (Système Nationale des Données de Santé, SNDS). Temporal trends were studied using linear regression models. Spatial distributions were studied using Moran's global index (I) and the statistical method and local indicators of spatial association. RESULTS: The incidence of permanent CH in females increased by 8.9% per year (2014: 36.9 [31.1-43.7] per 100,000 birth-years vs. 2019: 51 [43.9-59.3] per 100,000 birth-years, p < 0.01). The incidence of AH decreased between 2014 and 2019 for both females (2014: 535.7 [533.2-538.2] per 100,000 person-years vs 2019: 335.5 [333.6-337.4] per 100,000 person-years, p < 0.01) and males (2014: 197.5 [195.9-199] per 100,000 person-years vs 2019: 141.7 [140.4-142.9] per 100,000 person-years, p<0.01). The incidence of hypothyroidism was high in the Nord-Pas-De-Calais and Lorraine regions (CH and AH). CONCLUSIONS: The incidence of permanent CH in females has increased over time. AH incidence decreased. It seems necessary to investigate environmental factors in the disparity of incidence distribution.

Diabetes and cardiovascular risk according to sex: An overview of epidemiological data from the early Framingham reports to the cardiovascular outcomes trials.

Male sex is a major cardiovascular risk factor in the general population, with men showing higher age-adjusted prevalence of cardiovascular disease than women. Diabetes, another major cardiovascular risk factor, affects cardiovascular risk differentially between men and women. Data from prospective observational studies showed that women with diabetes had greater relative risk of cardiovascular events than men with diabetes, leading to a smaller difference between diabetic men and women than between non-diabetic men and women in terms of cardiovascular disease. This excess relative risk concerns cardiovascular death, coronary heart disease, stroke and heart failure. It is greatest in the youngest age group and decreases gradually with age. Although many mechanisms have been proposed to explain the greater cardiovascular burden in women with diabetes, little is known about the impact of diverse anti-hyperglycemic drugs on cardiovascular events according to sex. Hence, cardiovascular outcomes trials provide a unique opportunity to study the impact of novel anti-hyperglycemic drugs on cardiovascular outcomes in men and women with type-2 diabetes. Here, we present an overview of the epidemiological data concerning sex-related differences in cardiovascular disease in people with diabetes, with a focus on the effects of novel anti-hyperglycemic drugs on cardiovascular outcomes in men and women. In addition, we summarize proposed mechanisms to explain these differences, with relevant references for the interested reader.

Does prenatal exposure to multiple airborne and tap-water pollutants increase neonatal thyroid-stimulating hormone concentrations? Data from the Picardy region, France.

OBJECTIVE: Systematic screening for congenital hypothyroidism by heel-stick sampling has revealed unexpected heterogeneity in the geographic distribution of newborn thyroid-stimulating hormone concentrations in Picardy, France. We explored a possible relationship with environmental pollutants. METHODS: Zip code geolocation data from mothers of newborns without congenital hypothyroidism born in 2021 were linked to ecological data for a set of airborne (particulate matter with a diameter of 2.5 µm or less [PM2.5] or 10 µm or less [PM10]) and tap-water (nitrate and perchlorate ions and atrazine) pollutants. Statistical associations between mean exposure levels during the third trimester of pregnancy and Thyroid-stimulating hormone (TSH) concentrations in 6249 newborns (51 % male) were investigated using linear regression models. RESULTS: Median neonatal TSH concentration (interquartile range, IQR) was 1.7 (1-2.8) mIU/L. An increase of one IQR in prenatal exposure to perchlorate ions (3.6 µg/L), nitrate ions (19.2 mg/L), PM2.5 (3.7 µg/m3) and PM10 (3.4 µg/m3), were associated with increases in TSH concentrations of 2.30 % (95 % CI: 0.95-3.66), 5.84 % (95 % CI: 2.81-8.87), 13.44 % (95 % CI: 9.65-17.28) and 6.26 % (95 % CI: 3.01-9.56), respectively. CONCLUSIONS: Prenatal exposure to perchlorate and nitrate ions in tap water and to airborne PM over the third trimester of pregnancy was significantly associated with increased neonatal TSH concentrations.

Protection by metformin against severe Covid-19: An in-depth mechanistic analysis.

Since the outbreak of Covid-19, several observational studies on diabetes and Covid-19 have reported a favourable association between metformin and Covid-19-related outcomes in patients with type 2 diabetes mellitus (T2DM). This is not surprising since metformin affects many of the pathophysiological mechanisms implicated in SARS-CoV-2 immune response, systemic spread and sequelae. A comparison of the multifactorial pathophysiological mechanisms of Covid-19 progression with metformin's well-known pleiotropic properties suggests that the treatment of patients with this drug might be particularly beneficial. Indeed, metformin could alleviate the cytokine storm, diminish virus entry into cells, protect against microvascular damage as well as prevent secondary fibrosis. Although our in-depth analysis covers many potential metformin mechanisms of action, we want to highlight more particularly its unique microcirculatory protective effects since worsening of Covid-19 disease clearly appears as largely due to severe defects in the structure and functioning of microvessels. Overall, these observations confirm that metformin is a unique, pleiotropic drug that targets many of Covid-19's pathophysiology processes in a diabetes-independent manner.

Screening for sleep-disordered breathing in people with type 1 diabetes by combining polysomnography with glucose variability assessment.

AIMS: There are few published data on sleep-disordered breathing (SDB) in type 1 diabetes (T1DM). Here, we used a combination of polysomnography and glucose variability assessment to screen for SDB. METHODS: In a prospective, single-centre study, adults with T1DM underwent polysomnography and continuous glucose monitoring during a single night. We measured high glucose variability and the occurrence of a low or very low glucose level. Mild and moderate-to-severe SDB were defined as an apnoea-hypopnoea index above 5/h and 15/h, respectively. RESULTS: We studied 46 patients (25 men; median age: 42 [35-54]; diabetes duration: 18 years [13-29]; body mass index (BMI): 24.8 kg/m2 [23.0-28.9]). SDB was present in 17 patients (37.0%) overall (mild SDB: n = 9; moderate-to-severe SDB; n = 8). When compared with the absence of SDB or mild SDB, moderate-to-severe SDB was associated with a higher BMI (29.8 kg/m2 [27.8-31.1]) and a longer diabetes duration (26 years [18-31]) but not with above-target glucose variability or more sleep disorder symptoms. Conversely, sleep disorder symptoms were not more frequent in patients with above-target glucose variability. CONCLUSION: SDB was highly prevalent and associated with obesity. According to the methods used here, sleep disorders were not associated with above-target glucose variability or low glucose values.

Thyrotropin Levels in Patients with Coronavirus Disease 2019: Assessment during Hospitalization and in the Medium Term after Discharge.

BACKGROUND: The objectives of this study were (1) to compare TSH levels between inpatients with critical versus non-critical coronavirus disease 19 (COVID-19), and (2) to describe the status of TSH levels three months after hospitalization. METHODS: We collected data on adult patients hospitalized with COVID-19 at Amiens University Hospital. We compared TSH levels between inpatients with critical (intensive care unit admission and/or death) versus non-critical COVID-19. Thereafter, survivors were invited to return for a three-month post-discharge visit where thyroid function tests were performed, regardless of the availability of TSH measurement during hospitalization. RESULTS: Among 448 inpatients with COVID-19, TSH assay data during hospitalization were available for 139 patients without prior thyroid disease. Patients with critical and non-critical forms of COVID-19 did not differ significantly with regard to the median (interquartile range) TSH level (0.96 (0.68-1.71) vs. 1.27 mIU/L (0.75-1.79), p = 0.40). Abnormal TSH level was encountered in 17 patients (12.2%); most of them had subclinical thyroid disease. TSH assay data at the three-month post-discharge visit were available for 151 patients without prior thyroid disease. Only seven of them (4.6%) had abnormal TSH levels. Median TSH level at the post-discharge visit was significantly higher than median TSH level during hospitalization. CONCLUSIONS: Our findings suggest that COVID-19 is associated with a transient suppression of TSH in a minority of patients regardless of the clinical form. The higher TSH levels three months after COVID-19 might suggest recovery from non-thyroidal illness syndrome.

Pituitary apoplexy in the aftermath of a SARS-CoV-2 infection: a case series from Amiens University Hospital.

Objective: Since the outbreak of the COVID-19 pandemic, several cases of pituitary apoplexy (PA) following a SARS-CoV-2 infection have been described in several countries. Here, we describe a case series of PA occurring in the aftermath of a SARS-CoV-2 infection to alert physicians about possible neuro-endocrinological damage caused by the virus that can lead to visual sequelae and hypopituitarism. Design and methods: We retrospectively identified all the adult patients treated at Amiens University Hospital between March 2020 and May 2021 for PA confirmed by cerebral imaging and following an RT-PCR-confirmed SARS-CoV-2 infection. Results: Eight cases (six women, two men) occurred between March 2020 and May 2021 and were reviewed in this study. The mean age at diagnosis was 67.5 ± 9.8 years. Only one patient had a 'known' non-functional pituitary macroadenoma. The most common symptom of PA was a sudden headache. Brain imaging was typical in all cases. Only two patients required decompression surgery, whereas the others were managed conservatively. The clinical outcome was favorable for all patients but without recovery of their pituitary deficiencies. There was no diabetes insipidus. Conclusion: This case series, the largest in the literature, reinforces the strength, consistency, and coherence of the association between SARS-CoV-2 infection and PA. Our study provides support for the hypothesis that SARS-CoV-2 may be a new precipitating factor for PA. It is essential that practitioners be alerted about possible pituitary disease due to the virus so that such patients are recognized and appropriately managed, hence improving their prognosis.

Smoking and diabetes interplay: A comprehensive review and joint statement.

Evidence shows that smoking increases the risk of pre-diabetes and diabetes in the general population. Among persons with diabetes, smoking has been found to increase the risk of all-cause mortality and aggravate chronic diabetic complications and glycemic control. The current paper, which is a joint position statement by the French-Speaking Society on Tobacco (Société Francophone de Tabacologie) and the French-Speaking Society of Diabetes (Société Francophone du Diabète), summarizes the data available on the association between smoking and diabetes and on the impact of smoking and smoking cessation among individuals with type 1, type 2, and gestational diabetes mellitus. It also provides evidence-based information about the pharmacological and behavioral strategies for smoking cessation in these patients.

Clinical aspects of multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome characterized by the co-occurrence of primary hyperparathyroidism, duodenopancreatic neuroendocrine tumours (NETs) and/or pituitary adenomas. MEN1 can predispose patients to other endocrine and non-endocrine tumours, such as cutaneous tumours, central nervous system tumours and breast cancer. Endocrine tumours in patients with MEN1 differ from sporadic tumours in that they have a younger age at onset, present as multiple tumours in the same organ and have a different clinical course. Therefore, patients with overt MEN1 and those who carry a MEN1 mutation should be offered tailored biochemical and imaging screening to detect tumours and evaluate their progression over time. Fortunately, over the past 10 years, knowledge about the clinical phenotype of these tumours has markedly progressed, thanks to the implementation of national registries, particularly in France and the Netherlands. This Review provides an update on the clinical management of MEN1-related tumours. Epidemiology, the clinical picture, diagnostic work-up and the main lines of treatment for MEN1-related tumours are summarized. Controversial therapeutic aspects and issues that still need to be addressed are also discussed. Moreover, special attention is given to MEN1 manifestations in children and adolescents.