Blood glucose measurement remains a cornerstone in clinical biochemistry, playing a critical role in the diagnosis and monitoring of diabetes mellitus, including gestational diabetes. In France, the diagnosis of diabetes continues to rely exclusively on laboratory-based plasma or serum glucose measurement, as HbA1c is not currently accepted as a diagnostic marker. Nonetheless, several pre-analytical factors may compromise glucose measurement, particularly in vitro glycolysis, which can significantly reduce measured concentrations if not adequately controlled. In 2025, the French Society of Clinical Biology (SFBC) and the National College of Hospital Biochemistry (CNBH) established a working group with the following objectives: (i) to assess current laboratory practices for glucose measurement, and (ii) to review and update the available scientific literature to develop evidence-based recommendations. To achieve these goals, three thematic subgroups were created to conduct: 1) a literature review: focusing on pre-analytical variables, the analytical performance of blood collection tubes, the clinical indications for laboratory glucose testing, and the definition of context-specific reference values; 2) a field survey: designed to capture current practices among clinical biochemists in France and other French-speaking countries; 3) research studies involving on-site experimental trials to directly compare different methodological approaches and pre-analytical strategies. This initiative aims to provide a comprehensive overview of current practices, identify gaps in knowledge, and ultimately support the development of harmonized national recommendations for glucose measurement particularly in the diagnostic and clinical management of diabetes.

Résumé L’apolipoprotéine E (ApoE) est une glycoproteins clé du métabolisme lipidique cérébral, jouant un rôle déterminant dans la pathogenèse de la maladie d’Alzheimer (MA). Parmi ses trois isoformes principales – ApoE2, ApoE3 et ApoE4 –, l’allèle ε4 constitue le principal facteur de risque génétique connu de la MA sporadique. Les porteurs de l’allèle ε4 présentent un risque accru et une apparition plus précoce de la maladie. Sur le plan mécanistique, l’ApoE4 influence la clairance du peptide amyloïde β (Aβ), favorisant son accumulation et la formation de plaques séniles. Elle est également impliquée dans la dysfonction synaptique, la neuro-inflammation, et la déstabilisation du cytosquelette neuronal via la phosphorylation anormale de la protéine Tau. À l’inverse, l’ApoE2 exerce un effet protecteur potentiel, probablement par une meilleure régulation du métabolisme lipidique cérébral et une clairance accrue d’Aβ. Les avancées récentes, notamment l’approbation européenne du lecanemab (Leqembi®), confirment la pertinence des approches ciblant la cascade amyloïde. Cependant, les différences de réponse selon le génotype APOE soulignent la nécessité d’une médecine de précision. Cet article examine les mécanismes moléculaires reliant l’ApoE à la pathologie amyloïde et Tau, et discute des nouvelles perspectives thérapeutiques intégrant les traitements anti-Aβ et les stratégies de modulation d’ApoE.

BACKGROUND AND HYPOTHESIS:While physical activity (PA) is associated in observational studies with cardiovascular and renal protection few interventional studies have assessed its long-term effect on renal outcomes. This study is the first to specifically evaluate the impact of high-intensity PA on the slowing of renal function decline in type 2 diabetes (T2D) patients at high risk for kidney disease. METHODS:ActiDiaNe is an open, randomized controlled trial involving patients with T2D (pT2D) and rapid renal function decline (eGFR slope < -5 ml/min/year over 6-24 months). Participants were randomized to high-intensity PA (HIPA) or standard PA counseling (STPA) for two years. The primary endpoint was the slope of decline in cystatin C-derived eGFR (cys-eGFR). RESULTS:Across 21 centers, 178 patients were screened, 122 randomized, and 103 (29 women/74 men) analyzed for the primary endpoint (59 HIPA vs. 44 STPA). At baseline, mean age was 66 ± 8 years, median cys-eGFR was 54 ml/min/1.73m² (37; 65), and median eGFR decline was -9 ml/min/year (-12; -7). The primary endpoint showed a decline of -2.05 ml/min/year (95% CI: -3.46 to -0.64) in HIPA vs. -2.77 ml/min/year (95% CI: -4.40 to -1.14) in STPA (P = 0.512). Cardiovascular events and deaths occurred in 10 (17%) HIPA vs. 6 (14%) STPA patients (P = 0.646), with 3 deaths in HIPA (none of them protocol-related). Hypoglycemia was reported in 32 HIPA vs. 26 STPA patients (P = 0.623). CONCLUSION:In pT2D with rapid renal function decline, HIPA did not significantly alter renal function decline compared to STPA.

BACKGROUND:Methylglyoxal (MGO) is a potent glycating agent that contributes to the pathogenesis of diabetes. However, MGO is unstable in plasma without demanding sample preparation at blood collection, limiting its clinical utility as a biomarker. We aimed to discover reliable MGO-glycated albumin (ALB)-derived biomarkers and to assess their association with new-onset diabetes (NOD) in people with prediabetes. METHODS:Bottom-up mass spectrometry-based proteomics was used to discover peptide biomarkers of MGO-glycated ALB, including MGO-derived hydroimidazolone (MGH)-ALB219-225, which proved to be biologically stable and reliable for large-scale analyses in human plasma. After assay validation, the IT-DIAB (Innovation Thérapeutique DIABète) prospective study, conducted in 300 individuals with impaired fasting plasma glucose (FPG) levels (110 to 125 mg/dL, 6.1 to 6.9 mmol/L), was used to assess the association between plasma MGH-ALB219-225 and NOD, defined as FPG ≥126 mg/dL (7 mmol/L), using Kaplan-Meier curves and Cox models. RESULTS:In total, 113 participants of the IT-DIAB study developed NOD during a median follow-up of 5 years. There was a graded association between the baseline plasma MGH-ALB219-225 concentration and incident NOD (log-rank P < 0.0001), in contrast to a lack of association for plasma MGO and total or glycated ALB (commercial kit). After adjustment for age, sex, body mass index, FPG, hemoglobin (Hb) A1c, and ALB, the plasma levels of MGH-ALB219-225 were associated with NOD (hazard ratio [HR] per one SD [95% CI] = 1.50 [1.26-1.78]; P < 0.0001). CONCLUSIONS:MGH-ALB219-225 is a novel and stable peptide biomarker of MGO-glycated ALB, whose plasma levels are positively associated with an increased risk of NOD in individuals with prediabetes, independently of traditional risk factors. ClinicalTrials.gov Registration Number: NCT01218061.

The quantification of neurofilament light chain (NfL) in blood and cerebrospinal fluid (CSF) has proved useful in many contexts, for the diagnosis and prognosis of various neurological disorders. There is, however, a diversity of practices between centers, essentially linked to the context of use (COU), analytical methods, consideration of comorbidities, determination of cut-points or use of interpretation scales. Finally, for the same biochemical profile, the interpretation and reporting of results may differ from one center to another, raising the question of test commutability. To date, no consensus has been reached between the different laboratories involved to define the most appropriate conclusions/comments based on COU and cut-points. This work is an essential step towards consensual harmonization of the clinical use of NfL after CSF and/or blood analysis in various neurological contexts, as advocated by the Alzheimer's Association "Biofluid Based Biomarkers PIA" working group. This international project involves 58 clinical laboratories in 16 countries, specializing in the biochemical diagnosis of neurological disorders. By means of a questionnaire, we obtained a description of the COU, pre-analytical and analytical (biological fluid and method used to quantify NfL) protocols of all the centers involved. Of the centers, 42% quantified NfL in CSF, 29% in serum and 28% in plasma, and 1% in dried blood spot. The COUs were as follows: Frontotemporal dementia (FTD, 17%), Alzheimer's disease (AD, 16%), multiple sclerosis (MS, 16%), amyotrophic lateral sclerosis (ALS, 11%), psychiatric syndrome (PS, 10%), Creutzfeldt-Jakob disease (CJD, 8%), Parkinson's disease (PD, 8%), peripheral neuropathy (PN, 7%) and traumatic brain injury (TBI, 7%). Most centers define pathological cut-points based on published literature and take age into account (50%). Our initial results highlight the state of the art in terms of the clinical use of NfL analysis in CSF and blood in the context of different neurological diseases. We have now defined a coordinator for each COU subgroup and are organizing consensus meetings to harmonize the use and reporting of NfL measurements for the identified clinical applications. The results of these next steps will be presented.

AIM:Observational studies in the general population suggest that low concentrations of lipoprotein (a) [Lp(a)] are associated with an increased risk of type 2 diabetes. Here, we aim to determine whether Lp(a) plasma concentration and Kringle-IV (K-IV) repeat polymorphism were associated with new-onset diabetes (NOD) in individuals with prediabetes. METHODS:IT-DIAB is an observational, prospective study including 303 participants with impaired fasting glucose (fasting plasma glucose [FPG]: 110-125 mg/dl) followed annually for 5 years. The primary endpoint was the development of NOD, defined as a first FPG value ≥ 126 mg/dl during follow-up. Lp(a) concentrations were measured by immunoturbidimetry, apo(a) concentrations and the number of K-IV domains by mass spectrometry. Survival analyses for NOD were modeled using Kaplan-Meier curves and a multivariable Cox model, after binarization on threshold values of Lp(a) or K-IV. RESULTS:Among the participants, 113 (37%) developed NOD during follow-up. The concentrations of Lp(a) and the number of K-IV domains were not significantly different according to NOD status. Similarly, the percentage of patients with a non-detectable (≤ 7 nmol/l) or elevated (>125 nmol/l) Lp(a) concentration was similar between those with or without NOD: 68.1 vs 63.7% (P = 0.46) and 8.8 vs 8.9% (P > 0.99), respectively. Kaplan-Meier curves and Cox models did not show any association between Lp(a) concentration (threshold 7 nmol/l and 125 nmol/l) or number of K-IV domain (threshold 23) and the risk of NOD. CONCLUSION:In a high-risk population, Lp(a) concentration or polymorphic size do not appear to be substantially associated with type 2 diabetes risk.

Introduction: Iron and vitamin B12 deficiencies are common in patients with atrophic gastritis, but there are limited data on the prevalence of these deficiencies in different types of atrophic gastritis. Methods: This multicenter, prospective study assessed micronutrient concentrations in histologically confirmed autoimmune gastritis (AIG, n = 45), Helicobacter pylori-related non-autoimmune gastritis (NAIG, n = 109), and control patients (n = 201). A multivariate analysis was performed to determine factors influencing those deficiencies. Results: The median vitamin B12 concentration was significantly lower in AIG (367.5 pg/mL, Q1, Q3: 235.5, 524.5) than in NAIG (445.0 pg/mL, Q1, Q3: 355.0, 565.0, p = 0.001) and control patients (391.0 pg/mL, Q1, Q3: 323.5, 488.7, p = 0.001). Vitamin B12 deficiency was found in 13.3%, 1.5%, and 2.8% of AIG, NAIG, and control patients, respectively. Similarly, the median ferritin concentration was significantly lower in AIG (39.5 ng/mL, Q1, Q3: 15.4, 98.3 ng/mL) than in NAIG (80.5 ng/mL, Q1, Q3: 43.6, 133.9, p = 0.04) and control patients (66.5 ng/mL, Q1, Q3: 33.4, 119.8, p = 0.007). Iron deficiency and iron deficiency adjusted to CRP were present in 28.9% and 33.3% of AIG, 12.8% and 16.5% of NAIG, and 12.9% and 18.4% of controls, respectively. Multivariate analysis demonstrated that AIG patients had a higher risk of developing vitamin B12 deficiency (OR: 11.52 [2.85-57.64, p = 0.001]) and iron deficiency (OR: 2.92 [1.32-6.30, p = 0.007]) compared to control patients. Factors like age, sex, and H. pylori status did not affect the occurrence of vitamin B12 or iron deficiency. Conclusion: Iron and vitamin B12 deficiencies are more commonly observed in patients with AIG than in those with NAIG or control patients. Therefore, it is essential to screen for both iron and vitamin B12 deficiencies in AIG patients and include the treatment of micronutrient deficiencies in the management of atrophic gastritis patients.

OBJECTIVES:Hemolysis is a contributor to CS-AKI. Biochemistry analyzers provide a hemolysis index to quantify in vitro hemolysis, a condition that can, for example, affect the accuracy of potassium concentration measurements. We aimed to assess whether the postoperative plasma level of the hemolysis index (HIpostoperative) could aid the early recognition of patients at risk for cardiac surgery-associated acute kidney injury (CS-AKI) and also to evaluate other hemolysis indicators: plasma carboxyhemoglobin (COHbpostoperative) and methemoglobin (MetHbpostoperative). DESIGN:One-year retrospective study. SETTING:University hospital. PARTICIPANTS:Patients undergoing elective cardiac surgery. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:In 1090 patients, the median HIpostoperative was higher in patients who developed CS-AKI compared to patients who did not (11 mg/dL [interquartile range (IQR), 5-38 mg/dL] v 7 mg/dL [IQR, 3-16 mg/dL]; p < 0.001). HIpostoperative refined the early recognition of CS-AKI: the area under the precision-recall curve (AUPRC) for HIpostoperative was 37% (95% confidence interval [CI], 31%-42%), whereas the AUPRC associated with no discriminative power, equal to the prevalence of CS-AKI in the whole population, was 21%. Among the 611 patients with measurements for all 3 biomarkers, the AUPRC of HIpostoperative was higher than that of COHbpostoperative or MetHbpostoperative (+6.6% and +7.4% respectively; p < 0.0001 for both). Unlike COHbpostoperative or MetHbpostoperative, the incorporation of HIpostoperative into a model (trained on a sample then validated in another sample) of CS-AKI early recognition significantly enhanced its performance, with a +1.9% (95% CI, 1.6%-2.1%) increase in AUPRC (p < 0.0001). CONCLUSIONS:Elevated HIpostoperative represents an early alert signal for the development of CS-AKI. Our findings support the incorporation of HIpostoperative, a readily available biomarker, into predictive scores of CS-AKI.

The diagnosis ofsubarachnoid hemorrhage (SAH) is extremely important for appropriate management. Cerebral computed tomography (CT), used as the first-line investigation to detect bleeding, has excellent sensitivity if performed promptly, but its sensitivity falls sharply with the time elapsed since the onset of SAH. Oxyhemoglobin and bilirubin, the breakdown products of heme, are detectable in cerebrospinal fluid (CSF) by spectrophotometric absorption, which defines the search for xanthochromia pigment in CSF. Both parameters can be sought when imaging is negative or doubtful with a strong suspicion of SAH based on clinical signs. In this context, our working group at the Soci & eacute;t & eacute; Fran & ccedil;aise de Biologie Clinique (SFBC) is proposing recommendations to provide medical biologists with support for the implementation and validation of "oxyhemoglobin and bilirubin in CSF" test and enabling them to play their part in the diagnostic process. From the pre-analytical stages through to the delivery of results, we will summarize the pitfalls to be avoided, the main decision values and different physiological and pathological profiles.

Over the recent decades, the development of animal models allowed us to better understand various pathologies and identify new treatments. Hemorrhagic shock, i.e., organ failure due to rapid loss of a large volume of blood, is associated with a highly complex pathophysiology involving several pathways. Numerous existing animal models of hemorrhagic shock strive to replicate what happens in humans, but these models have limits in terms of clinical relevance, reproducibility, or standardization. The aim of this study was to refine these models to develop a new model of hemorrhagic shock. Briefly, hemorrhagic shock was induced in male Wistar Han rats (11-13 weeks old) by a controlled exsanguination responsible for a drop in the mean arterial pressure. The next phase of 75 min was to maintain a low mean arterial blood pressure, between 32 mmHg and 38 mmHg, to trigger the pathophysiological pathways of hemorrhagic shock. The final phase of the protocol mimicked patient care with an administration of intravenous fluids, Ringer Lactate solution, to elevate the blood pressure. Lactate and behavioral scores were assessed 16 h after the protocol started, while hemodynamics parameters and plasmatic markers were evaluated 24 h after injury. Twenty-four hours post-hemorrhagic shock induction, the mean arterial and diastolic blood pressure were decreased in the hemorrhagic shock group (p < 0.05). Heart rate and systolic blood pressure remained unchanged. All organ damage markers were increased with the hemorrhagic shock (p < 0.05). The lactatemia and behavioral scores were increased compared to the sham group (p < 0.05). In conclusion, we demonstrated that the protocol described here is a relevant model of hemorrhagic shock that can be used in subsequent studies, particularly to evaluate the therapeutic potential of new molecules.

Background: The impact of parathyroidectomy on bone mineral density in men with primary hyperparathyroidism is poorly known. This study aimed to evaluate the bone mineral density and bone remodeling biomarker changes in men with primary hyperparathyroidism 1 year after parathyroidectomy.Methods: Men operated for sporadic primary hyperparathyroidism between 2016 and 2022, enrolled in a monocentric prospective cohort, were analyzed. Patients with follow-up <1 year or missing data were excluded. Bone mineral density (dual X-ray absorptiometry) was measured before and 12 months after parathyroidectomy. Bone mineral density change >= 0.03g/cm(2) was deemed significant. Bone remodeling biomarkers were serum cross-linked C-telopeptide, procollagen type 1 N-terminal propeptide, and bone-specific alkaline phosphatases.Results: Forty-five men were included (mean age 58.8 +/- 13.1 years). Before surgery, 49% had osteopenia, and 11% had osteoporosis. Mean serum calcium and median serum parathyroid hormone levels decreased significantly after surgery (P < .0001). One year after parathyroidectomy, the mean bone mineral density increased significantly at the lumbar spine (+0.04g/cm(2) [0.01;0.70], P = .0054), femoral neck (+0.04g/cm(2) [0.03;0.05], P < .0001) and total hip (+0.02g/cm(2) [0.01;0.03], P = .0002). Considering significant bone mineral density gain (+1 point) and loss (-1 point) at each site, 29/45 patients (64% [95% CI 49;78]) improved. Bone remodeling biomarker concentrations significantly decreased (P < .001). Conclusion: Parathyroidectomy positively affects bone mineral density in men with primary hyper-parathyroidism, supporting osteopenia as a surgical indication in these patients.(c) 2023 Elsevier Inc. All rights reserved.

Résumé L’augmentation de troponine hors contexte de syndrome coronarien aigu représente une réalité au quotidien et concerne 40 % des demandes de dosage des services d’urgences. Dans l’infarctus du myocarde (IDM), l’augmentation de la troponine cardiaque est liée à la nécrose des cardiomyocytes. Mais toute lésion des cardiomyocytes, réversible ou irréversible, peut s’accompagner d’une augmentation de troponine cardiaque. Il convient de savoir distinguer les causes sans réel impact délétère, comme l’exercice physique intense, des nombreuses causes pathologiques où la valeur élevée de troponine cardiaque constitue un facteur pronostique : insuffisance rénale, embolie pulmonaire, sepsis, chirurgie non cardiaque. La particularité de l’augmentation de la seule troponine T cardiaque dans différentes atteintes musculaires semble de plus en plus fréquente et amène à s’interroger sur la nécessité de disposer du dosage à la fois de troponine T cardiaque et de troponine I cardiaque.