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/m
2
; 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, HbA
1c
, 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.
Regulation of food intake is a recently identified endocrine function of bone that is mediated by Lipocalin-2 (LCN2). Osteoblast-secreted LCN2 suppresses appetite and decreases fat mass while ...improving glucose metabolism. We now show that serum LCN2 levels correlate with insulin levels and β-cell function, indices of healthy glucose metabolism, in obese mice and obese, prediabetic women. However, LCN2 serum levels also correlate with body mass index and insulin resistance in the same individuals and are increased in obese mice. To dissect this apparent discrepancy, we modulated LCN2 levels in mice. Silencing Lcn2 expression worsens metabolic dysfunction in genetic and diet-induced obese mice. Conversely, increasing circulating LCN2 levels improves metabolic parameters and promotes β-cell function in mouse models of β-cell failure acting as a growth factor necessary for β-cell adaptation to higher metabolic load. These results indicate that LCN2 up-regulation is a protective mechanism to counteract obesity-induced glucose intolerance by decreasing food intake and promoting adaptive β-cell proliferation.
Purpose of Review
In France, in order to describe the phenotypic characteristics of patients with diabetes hospitalized for coronavirus disease-2019 (COVID-19) and to identify the prognostic factors ...in this specific population, the CORONADO (CORONAvirus and Diabetes Outcomes) study was launched. This review will summarize the key findings from the CORONADO study and put them in perspectives with others studies published on the subject.
Recent Findings
For almost 2 years, the new SARS-CoV-2 (Severe Acute Respiratory Syndrome-CoronaVirus-2), which causes COVID-19, has spread all around the world leading to a pandemic. From the first epidemiological reports, diabetes mellitus has rapidly emerged as a major risk factor associated with severe forms of COVID-19 but few data were available about diabetes characteristics in hospitalized people with COVID-19.
Summary
Between March 10 and April 10, 2020, 2951 patients were included in 68 centers throughout the national territory, including overseas territories. In the CORONADO study, the primary outcome was a composite endpoint combining invasive mechanical ventilation (IMV) and/or death within day 7 (D7). Secondary outcomes included death, IMV, intensive care unit (ICU) admission, and hospital discharge, all considered within D7 and day 28 (D28). The primary outcome occurred in 29.0% participants within D7 following hospital admission. Within D28, the end of the follow-up period, the mortality rate was 20.6%, while 50.2% of patients were discharged. In multivariable analysis, advanced age, microvascular complications, treatment with insulin or statin prior to admission, dyspnea on admission, as well as biological markers reflecting the severity of the infection (high levels of transaminases, leukocytes and CRP, and low platelet levels) were associated with an increased risk of death. Several exploratory analyses were performed to clarify the influence of some parameters such as weight status, sex, type of diabetes, and some routine drugs, including metformin or statins.
In patients at metabolic risk, nonalcoholic fatty liver disease is a strong and highly prevalent predictor for type 2 diabetes. Its assessment in clinical practice is not easy but the fatty liver ...index (FLI) could be used as a surrogate. Here, we studied the association between the FLI and the conversion to new-onset diabetes (NOD) or prediabetes reversion in patients with prediabetes.
The IT-DIAB observational study included 389 individuals with prediabetes, defined as fasting plasma glucose (FPG) between 110 and 125 mg/dL. NOD conversion was defined as a first FPG value ≥ 126 mg/dL and prediabetes reversion as a first FPG value < 110 mg/dL. The associations of both events with baseline FLI were studied separately using multivariate Cox models.
After a median follow-up of 3.9 years (range 0.1-6.1), 138 individuals (35.5%) converted to NOD. FLI was associated with a higher risk of NOD conversion (unadjusted HR per SD = 1.54, 95%CI 1.27-1.86, p<0.0001), even after multiple adjustment on FPG, HbA1c and diabetes risk score (adjusted HR per SD 1.31, 95%CI 1.07-1.61, p = 0.008). FLI was also associated with prediabetes reversion: adjusted HR per SD = 0.85, 95%CI 0.75-0.96, p = 0.0077. Changes in FLI were significantly associated with changes in FPG during follow-up (p<0.0001). When compared to a full model including the diabetes risk score, FPG, HbA1C and FLI, only HbA1C added a significant prediction information (AUROC: 72.8% for full model vs 69.4% for the model without HbA1C; p = 0.028), while the removal of FLI to the full model did not alter its predictive value (AUROC 72.2%). The predictive value for NOD conversion was not significantly better for HOMA-IR compared to FLI (AUROC: 69.3 vs 63.7%, p = 0.067).
FLI is a simple, practical score to further stratify the risk of conversion to NOD or the possibility of prediabetes reversion in clinical practice, independently of classical glucose parameters.
ClincialTrials.gov number NCT01218061 and NCT01432509.
Objective
To evaluate the association of ulnar artery occlusion (UAO) assessed using Doppler ultrasound (DUS) with the severity markers of systemic sclerosis (SSc).
Methods
Two hundred four ...unselected patients fulfilling the American College of Rheumatology/European League Against Rheumatism 2013 classification criteria for SSc were included in this cross‐sectional multicenter study. All patients underwent bilateral hand DUS to evaluate the presence of UAO and clinical/paraclinical visceral evaluation according to current guidelines. Univariable and multivariable ordinal regression models were applied, grading the severity of UAO as “no UAO,” “only one UAO,” and “UAO on both hands,” and assessing its association with clinical features of SSc. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.
Results
UAO was found in 76 patients (37.3%) and was bilateral in 49 patients (24%). UAO as an ordinal event was significantly associated with disease duration, history of fingertip ulcers, telangiectasia, higher modified Rodnan skin thickness score (MRSS), worse diffusing capacity for carbon monoxide (DLco) values, higher tricuspid jet velocity, late capillaroscopic pattern, and positivity for anticentromere antibodies (ACAs) (univariable analysis). In the adjusted multivariable ordinal model, UAO was less frequent in women (OR 0.35 95% CI 0.15–0.83, P = 0.017) and in patients receiving steroids (OR 0.24 95% CI 0.09–0.62, P = 0.0034). In multivariable analyses, significant association with UAO was retained for history of fingertip ulcers (OR 2.55 95% CI 1.24–5.21, P = 0.011), higher MRSS (OR 1.65 95% CI 1.06–2.56, P =0.025), lower DLco values (OR 0.85 95% CI 0.78–0.94, P = 0.0015), and ACA positivity (OR 2.89 95% CI 1.36–6.11, P = 0.0056).
Conclusion
UAO may represent a relevant severity marker of vasculopathy in SSc. Its predictive value for the onset of severe vascular manifestations such as pulmonary arterial hypertension, and its association with mortality, remain to be determined in longitudinal studies.
The identification of circulating biomarkers associated with the risk of type 2 diabetes (T2D) is useful for improving the current prevention strategies in the most at-risk patients. Here, we aimed ...to investigate the association of plasma apolipoprotein concentrations in prediabetes subjects with the incidence of new-onset T2D during follow-up.
In the IT-DIAB prospective study, 307 participants with impaired fasting glucose levels (fasting plasma glucose FPG: 110-125 mg/dL) were followed yearly for 5 years. The onset of T2D was defined as a first FPG value ≥ 126 mg/dL during follow-up. Apolipoprotein (apo)A-I, A-II, A-IV, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a) plasma concentrations were determined by mass spectrometry. Correlations between apolipoproteins and metabolic parameters at baseline were assessed by Spearman's coefficients. Kaplan-Meier curves were drawn using a ternary approach based on terciles and incident T2D. The association between plasma apolipoproteins concentrations and the incidence of T2D was determined using Cox proportional-hazards models.
During a median follow-up of 5-year, 115 participants (37.5%) developed T2D. After adjustment for age, sex, body mass index, FPG, HbA
, and statin use, the plasma levels of apoC-I, apoC-II, apoC-III, apoE, apoF, apoH, apoJ, and apoL1 were positively associated with a high risk for T2D. After further adjustment for plasma triglycerides, only apoE (1 SD natural-log-transformed hazard ratio: 1.28 95% confidence interval: 1.06; 1.54; p = 0.010), apoF (1.22 1.01; 1.48; p = 0.037), apoJ (1.24 1.03; 1.49; p = 0.024), and apoL1 (1.26 1.05; 1.52; p = 0.014) remained significantly associated with the onset of T2D. Kaplan-Meier survival curves also showed that the lower third of plasma apoE levels (< 5.97 mg/dL) was significantly associated with a lower risk of conversion to T2D (log-rank test, p = 0.002) compared to the middle and upper thirds.
The plasma apoE levels are positively associated with the risk of T2D in prediabetes subjects, independently of traditional risk factors. The possible associations of apoF, apoJ, and apoL1 with T2D risk also pave the way for further investigations. Trial registration This trial was registered at clinicaltrials.gov as NCT01218061 and NCT01432509.
Oncocytic adrenocortical tumors are a rare subtype of adrenal tumors with challenging diagnosis and histoprognostic assessment. It is usually believed that oncocytic adrenocortical tumors have a more ...indolent clinical behavior than conventional adrenocortical tumors. As the Weiss score overestimates the malignancy of oncocytic adrenocortical tumors owing to intrinsic parameters, alternative scores have been proposed. The Lin–Weiss–Bisceglia score is currently recommended. We performed a large nationwide multicenter retrospective clinicopathologic study of oncocytic adrenocortical tumors. Among the 43 patients in our cohort, 40 patients were alive without disease, 2 patients died of their disease and 1 patient was alive with relapse after a median follow-up of 38 months (20–59). Our data revealed that over 50% of the oncocytic adrenocortical tumor cases were diagnosed as carcinoma whatever the classification systems used, including the Lin–Weiss–Bisceglia score. The exception is the Helsinki score, which incorporates the Ki-67 proliferation index and was the most specific prognostic score for oncocytic adrenocortical tumor malignancy without showing a loss in sensitivity. A comparison of malignant oncocytic adrenocortical tumors with conventional adrenocortical carcinomas matched for age, sex, ENS@T stage and surgical resection status showed significant better overall survival of malignant oncocytic adrenocortical tumors.
Background
Persistent primary hyperparathyroidism (PHPT) occurs in 2.5% to 15% of cases after parathyroidectomy. Few studies have evaluated the best pre-reoperative imaging approaches for persistent ...sporadic PHPT. This retrospective multicenter study aimed to evaluate the benefit of a second pre-reoperative
99m
Tc-methoxy-isobutyl-isonitrile (MIBI) scintigraphy for patients with persistent PHPT who had a
99m
Tc-MIBI before their initial surgery.
Methods
The study enrolled 50 patients with persistent sporadic PHPT who had reoperation between 2006 and 2016 in three French University Hospitals (Angers, Nantes, and La Pitié Salpêtrière-Paris). Preoperative
99m
Tc-MIBI scan was performed before each operation.
Results
After the reoperation, 42 patients (84%) were cured. By the second
99m
Tc-MIBI, 31 patients (62%) had a removed gland identified. A new pathologic gland was identified by a second
99m
Tc-MIBI in 25 patients (50%), and this imaging permitted correction of an initial surgical error in six patients (12%). A second
99m
Tc-MIBI showed a sensitivity of 63%, a specificity of 89%, a positive predictive value (PPV) of 78%, and a negative predictive value (NPV) of 80%. A concordant second
99m
Tc-MIBI and ultrasonography (17 patients) showed a sensitivity of 70%, a specificity of 81%, a PPV of 70%, and an NPV of 81%.
Conclusions
Performing a second
99m
Tc-MIBI scan permitted 62% of the persistent PHPT patients to be cured, allowing identification of new pathologic glands in 50% of the cases and correction of an initial surgical error in 12% of the cases, with high specificity and PPV. These results reinforce the fact that a second
99m
Tc-MIBI scan should be performed at first intention before reoperation of patients with persistent PHPT, regardless of the result from the initial
99m
Tc-MIBI scan.
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