Validation of the Body Scan®, a new device to detect small fiber neuropathy by assessment of the sudomotor function: agreement with the Sudoscan®

BackgroundSudomotor dysfunction is one of the earliest manifestations of small fiber neuropathy (SFN), reflecting the alteration of sympathetic C fiber innervation of the sweat glands. Among other techniques, such innervation can be assessed by measuring electrochemical skin conductance (ESC) in microsiemens (μS). In this study, ESC was measured at the feet to detect distal SFN. For this objective, the performance of a new device, the Body Scan® (Withings, France), intended for home use, was compared with that of a reference device, the Sudoscan® (Impeto Medical, France), which requires a hospital setting.MethodsIn patients with diabetes with or without neuropathy or non-diabetic patients with lower-limb neuropathy, the diagnostic performance of the Body Scan® measurement was assessed by calculating its sensitivity (Se) and specificity (Sp) to detect at least moderate SFN (Se70 and Sp70), defined by a value of feet ESC ≤ 70 μS and > 50 μS on the Sudoscan® measure, or severe SFN (Se50 and Sp50), defined by a value of feet ESC ≤ 50 μS on the Sudoscan® measure. The agreement between the two devices was assessed with the analysis of Bland–Altman plots, mean absolute error (MAE), and root mean squared error (RMSE) calculations. The repeatability of the measurements was also compared between the two devices.ResultsA total of 147 patients (52% men, mean age 59 years old, 76% diabetic) were included in the analysis. The sensitivity and specificity to detect at least moderate or severe SFN were: Se70 = 0.91 ([0.83, 0.96]), Sp70 = 0.97 ([0.88, 0.99]), Se50 = 0.91 ([0.80, 0.98]), and Sp50 = 0.99 ([0.94, 1]), respectively. The bias and 95% limits of agreement were 1.5 [−5.4, 8.4]. The MAE was 2.9 and the RMSE 3.8. The intra-sample variability was 2.0 for the Body Scan® and 2.3 for the Sudoscan®.ConclusionThe ESC measurements provided by the Body Scan® were in almost perfect agreement with those provided by the reference device, the Sudoscan®, which validates the accuracy of the Body Scan® for the detection of SFN. By enabling simple, rapid, and autonomous use by the patient at home, this new technique will facilitate screening and monitoring of SFN in daily practice.Clinical trial registrationClinicalTrials.gov, identifier NCT05178459

Etude du rôle des monocytes dans la pathogénèse du diabète et de ses complications

Introduction : Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular(CV) events and severe forms of COVID19. T2DM, atherosclerosis and COVID-19 have pathogenesis related to a pathological inflammatory state. Monocytes (Mono) have both pro- and anti-inflammatory capacities, they are also able to infiltrate tissues and to differentiate into macrophages. We are testing the hypothesis that mono could be associated with the onset of diabetes, atherosclerosis and severe COVID19. Methods : The Mono (totals and subtypes) of a T2DM cohort were quantified (by immunophenotyping (IP)), their correlations with clinicobiological and CV data were studied. The gestational diabetes model was used to assess monocytic changes between normoglycemia (NG), pre-diabetes (PrDt) and T2DM. The relationship between lipidomas and the characteristics of Monos has been studied. Mono from patients hospitalized for severe COVID19 were caracterised by IP and then compared between T2DM and healthy. Results : In the T2D population, the Mono count is associated with sex, smoking, serum creatinine and RCV. Only classical Monos (MC) are associated with the RCV. The percentage of MC increases between NG, PrDt and DT2 but no relation was identified with the lipidomic changes. T2D / COVID19 patients had less mono (decrease in CD) compared to non-T2D / COVID19, but larger ones. Conclusion : Due to their distributional modifications, Mono appears to be associated with the pathogenesis of T2DM and its complications. However, their exact roles remain to be explored.Introduction: Les patients diabétiques de type 2 (DT2) sont à haut risque de complications cardiovasculaires (CV) et de formes graves de COVID19. Le DT2, l’athérosclérose et le COVID-19 ont une pathogenèse liée à un état inflammatoire pathologique. Les monocytes (Mono) sont capables d’avoir une action propre anti- ou pro-inflammatoire, mais aussi de s’infiltrer dans les tissus et de s’y différencier en macrophages. Nous testons l’hypothèse qu’ils pourraient être associés à la mise en place du diabète et de ces 2 complications. Méthodes : Les Mono (totaux et sous-types) d’une cohorte de DT2 ont été quantifiés (en immunophénotypage(IP)), leurs corrélations avec les données clinicobiologiques et CV ont été étudiées. Le modèle du diabète gestationnel a été utilisé pour évaluer les changements monocytaires entre normo-glycémie (NG), pré-diabète(PrDt) et DT2. La relation entre leurs lipidomes et les caractéristiques des Mono a été étudiée. Les Mono analysés par IP de patients hospitalisés pour COVID19 sévère, DT2 ou non, ont été comparés. Résultats : Dans la population DT2, le compte de Mono est associé au sexe, au tabagisme, à la créatininémie et au RCV. Seuls les Mono classiques (MC) sont associés au RCV. Le pourcentage de MC augmente entre NG, PrDt et DT2 sans relation identifiée avec les modifications lipidomiques. Les patients DT2/COVID19 avaient une moins de mono (diminution des MC) par rapport aux non-DT2/COVID19, mais des plus gros. Conclusion : De par leurs modifications de répartition, les Mono semblent bien associés à la pathogenèse du DT2 et de ses complications. Néanmoins leurs rôles exacts restent à explorer avant de pouvoir imaginer en faire une cible thérapeutique

Etude du rôle des monocytes dans la pathogénèse du diabète et de ses complications

Introduction : Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular(CV) events and severe forms of COVID19. T2DM, atherosclerosis and COVID-19 have pathogenesis related to a pathological inflammatory state. Monocytes (Mono) have both pro- and anti-inflammatory capacities, they are also able to infiltrate tissues and to differentiate into macrophages. We are testing the hypothesis that mono could be associated with the onset of diabetes, atherosclerosis and severe COVID19. Methods : The Mono (totals and subtypes) of a T2DM cohort were quantified (by immunophenotyping (IP)), their correlations with clinicobiological and CV data were studied. The gestational diabetes model was used to assess monocytic changes between normoglycemia (NG), pre-diabetes (PrDt) and T2DM. The relationship between lipidomas and the characteristics of Monos has been studied. Mono from patients hospitalized for severe COVID19 were caracterised by IP and then compared between T2DM and healthy. Results : In the T2D population, the Mono count is associated with sex, smoking, serum creatinine and RCV. Only classical Monos (MC) are associated with the RCV. The percentage of MC increases between NG, PrDt and DT2 but no relation was identified with the lipidomic changes. T2D / COVID19 patients had less mono (decrease in CD) compared to non-T2D / COVID19, but larger ones. Conclusion : Due to their distributional modifications, Mono appears to be associated with the pathogenesis of T2DM and its complications. However, their exact roles remain to be explored.Introduction: Les patients diabétiques de type 2 (DT2) sont à haut risque de complications cardiovasculaires (CV) et de formes graves de COVID19. Le DT2, l’athérosclérose et le COVID-19 ont une pathogenèse liée à un état inflammatoire pathologique. Les monocytes (Mono) sont capables d’avoir une action propre anti- ou pro-inflammatoire, mais aussi de s’infiltrer dans les tissus et de s’y différencier en macrophages. Nous testons l’hypothèse qu’ils pourraient être associés à la mise en place du diabète et de ces 2 complications. Méthodes : Les Mono (totaux et sous-types) d’une cohorte de DT2 ont été quantifiés (en immunophénotypage(IP)), leurs corrélations avec les données clinicobiologiques et CV ont été étudiées. Le modèle du diabète gestationnel a été utilisé pour évaluer les changements monocytaires entre normo-glycémie (NG), pré-diabète(PrDt) et DT2. La relation entre leurs lipidomes et les caractéristiques des Mono a été étudiée. Les Mono analysés par IP de patients hospitalisés pour COVID19 sévère, DT2 ou non, ont été comparés. Résultats : Dans la population DT2, le compte de Mono est associé au sexe, au tabagisme, à la créatininémie et au RCV. Seuls les Mono classiques (MC) sont associés au RCV. Le pourcentage de MC augmente entre NG, PrDt et DT2 sans relation identifiée avec les modifications lipidomiques. Les patients DT2/COVID19 avaient une moins de mono (diminution des MC) par rapport aux non-DT2/COVID19, mais des plus gros. Conclusion : De par leurs modifications de répartition, les Mono semblent bien associés à la pathogenèse du DT2 et de ses complications. Néanmoins leurs rôles exacts restent à explorer avant de pouvoir imaginer en faire une cible thérapeutique

Etude du rôle des monocytes dans la pathogénèse du diabète et de ses complications

Introduction : Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular(CV) events and severe forms of COVID19. T2DM, atherosclerosis and COVID-19 have pathogenesis related to a pathological inflammatory state. Monocytes (Mono) have both pro- and anti-inflammatory capacities, they are also able to infiltrate tissues and to differentiate into macrophages. We are testing the hypothesis that mono could be associated with the onset of diabetes, atherosclerosis and severe COVID19. Methods : The Mono (totals and subtypes) of a T2DM cohort were quantified (by immunophenotyping (IP)), their correlations with clinicobiological and CV data were studied. The gestational diabetes model was used to assess monocytic changes between normoglycemia (NG), pre-diabetes (PrDt) and T2DM. The relationship between lipidomas and the characteristics of Monos has been studied. Mono from patients hospitalized for severe COVID19 were caracterised by IP and then compared between T2DM and healthy. Results : In the T2D population, the Mono count is associated with sex, smoking, serum creatinine and RCV. Only classical Monos (MC) are associated with the RCV. The percentage of MC increases between NG, PrDt and DT2 but no relation was identified with the lipidomic changes. T2D / COVID19 patients had less mono (decrease in CD) compared to non-T2D / COVID19, but larger ones. Conclusion : Due to their distributional modifications, Mono appears to be associated with the pathogenesis of T2DM and its complications. However, their exact roles remain to be explored.Introduction: Les patients diabétiques de type 2 (DT2) sont à haut risque de complications cardiovasculaires (CV) et de formes graves de COVID19. Le DT2, l’athérosclérose et le COVID-19 ont une pathogenèse liée à un état inflammatoire pathologique. Les monocytes (Mono) sont capables d’avoir une action propre anti- ou pro-inflammatoire, mais aussi de s’infiltrer dans les tissus et de s’y différencier en macrophages. Nous testons l’hypothèse qu’ils pourraient être associés à la mise en place du diabète et de ces 2 complications. Méthodes : Les Mono (totaux et sous-types) d’une cohorte de DT2 ont été quantifiés (en immunophénotypage(IP)), leurs corrélations avec les données clinicobiologiques et CV ont été étudiées. Le modèle du diabète gestationnel a été utilisé pour évaluer les changements monocytaires entre normo-glycémie (NG), pré-diabète(PrDt) et DT2. La relation entre leurs lipidomes et les caractéristiques des Mono a été étudiée. Les Mono analysés par IP de patients hospitalisés pour COVID19 sévère, DT2 ou non, ont été comparés. Résultats : Dans la population DT2, le compte de Mono est associé au sexe, au tabagisme, à la créatininémie et au RCV. Seuls les Mono classiques (MC) sont associés au RCV. Le pourcentage de MC augmente entre NG, PrDt et DT2 sans relation identifiée avec les modifications lipidomiques. Les patients DT2/COVID19 avaient une moins de mono (diminution des MC) par rapport aux non-DT2/COVID19, mais des plus gros. Conclusion : De par leurs modifications de répartition, les Mono semblent bien associés à la pathogenèse du DT2 et de ses complications. Néanmoins leurs rôles exacts restent à explorer avant de pouvoir imaginer en faire une cible thérapeutique

Study of the role of monocytes in the pathogenesis of diabetes and its complications

Introduction: Les patients diabétiques de type 2 (DT2) sont à haut risque de complications cardiovasculaires (CV) et de formes graves de COVID19. Le DT2, l’athérosclérose et le COVID-19 ont une pathogenèse liée à un état inflammatoire pathologique. Les monocytes (Mono) sont capables d’avoir une action propre anti- ou pro-inflammatoire, mais aussi de s’infiltrer dans les tissus et de s’y différencier en macrophages. Nous testons l’hypothèse qu’ils pourraient être associés à la mise en place du diabète et de ces 2 complications. Méthodes : Les Mono (totaux et sous-types) d’une cohorte de DT2 ont été quantifiés (en immunophénotypage(IP)), leurs corrélations avec les données clinicobiologiques et CV ont été étudiées. Le modèle du diabète gestationnel a été utilisé pour évaluer les changements monocytaires entre normo-glycémie (NG), pré-diabète(PrDt) et DT2. La relation entre leurs lipidomes et les caractéristiques des Mono a été étudiée. Les Mono analysés par IP de patients hospitalisés pour COVID19 sévère, DT2 ou non, ont été comparés. Résultats : Dans la population DT2, le compte de Mono est associé au sexe, au tabagisme, à la créatininémie et au RCV. Seuls les Mono classiques (MC) sont associés au RCV. Le pourcentage de MC augmente entre NG, PrDt et DT2 sans relation identifiée avec les modifications lipidomiques. Les patients DT2/COVID19 avaient une moins de mono (diminution des MC) par rapport aux non-DT2/COVID19, mais des plus gros. Conclusion : De par leurs modifications de répartition, les Mono semblent bien associés à la pathogenèse du DT2 et de ses complications. Néanmoins leurs rôles exacts restent à explorer avant de pouvoir imaginer en faire une cible thérapeutique.Introduction : Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular(CV) events and severe forms of COVID19. T2DM, atherosclerosis and COVID-19 have pathogenesis related to a pathological inflammatory state. Monocytes (Mono) have both pro- and anti-inflammatory capacities, they are also able to infiltrate tissues and to differentiate into macrophages. We are testing the hypothesis that mono could be associated with the onset of diabetes, atherosclerosis and severe COVID19. Methods : The Mono (totals and subtypes) of a T2DM cohort were quantified (by immunophenotyping (IP)), their correlations with clinicobiological and CV data were studied. The gestational diabetes model was used to assess monocytic changes between normoglycemia (NG), pre-diabetes (PrDt) and T2DM. The relationship between lipidomas and the characteristics of Monos has been studied. Mono from patients hospitalized for severe COVID19 were caracterised by IP and then compared between T2DM and healthy. Results : In the T2D population, the Mono count is associated with sex, smoking, serum creatinine and RCV. Only classical Monos (MC) are associated with the RCV. The percentage of MC increases between NG, PrDt and DT2 but no relation was identified with the lipidomic changes. T2D / COVID19 patients had less mono (decrease in CD) compared to non-T2D / COVID19, but larger ones. Conclusion : Due to their distributional modifications, Mono appears to be associated with the pathogenesis of T2DM and its complications. However, their exact roles remain to be explored

Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study

International audienceAims Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe T2D study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. Methods We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of Liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs. We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and 3D vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. Results In the cohort of 3154 T2D patients, 10 % displayed severe DR. In multivariate analysis, sex, disease duration, HbA1c, micro and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (OR1.139 [0.800-1.622], p=0.47). We further showed no effect of Liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. Conclusions The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR

Long-term Metabolic and Socioeducational Outcomes of Transient Neonatal Diabetes: A Longitudinal and Cross-sectional Study.

Transient neonatal diabetes mellitus (TNDM) occurs during the 1st year of life and remits during childhood. We investigated glucose metabolism and socioeducational outcomes in adults. We included 27 participants with a history of TNDM currently with (n = 24) or without (n = 3) relapse of diabetes and 16 non-TNDM relatives known to be carriers of causal genetic defects and currently with (n = 9) or without (n = 7) diabetes. Insulin sensitivity and secretion were assessed by hyperinsulinemic-euglycemic clamp and arginine-stimulation testing in a subset of 8 TNDM participants and 7 relatives carrying genetic abnormalities, with and without diabetes, compared with 17 unrelated control subjects without diabetes. In TNDM participants, age at relapse correlated positively with age at puberty (P = 0.019). The mean insulin secretion rate and acute insulin response to arginine were significantly lower in TNDM participants and relatives of participants with diabetes than in control subjects (median 4.7 [interquartile range 3.7-5.7] vs. 13.4 [11.8-16.1] pmol/kg/min, P < 0.0001; and 84.4 [33.0-178.8] vs. 399.6 [222.9-514.9] µIU/mL, P = 0.0011), but were not different between participants without diabetes (12.7 [10.4-14.3] pmol/kg/min and 396.3 [303.3-559.3] µIU/mL, respectively) and control subjects. Socioeducational attainment was lower in TNDM participants than in the general population, regardless of diabetes duration. Relapse of diabetes occurred earlier in TNDM participants compared with relatives and was associated with puberty. Both groups had decreased educational attainment, and those with diabetes had lower insulin secretion capacity; however, there was no difference in insulin resistance in adulthood. These forms of diabetes should be included in maturity-onset diabetes of the young testing panels, and relatives of TNDM patients should be screened for underlying defects, as they may be treated with drugs other than insulin

Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID ‐19 in type 2 diabetes

International audienceEarly in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk factor for severe disease and mortality. Inflammation is central to the aetiology of both conditions where variations in immune responses can mitigate or aggravate disease course. Identifying at-risk groups based on immunoinflammatory signatures is valuable in directing personalised care and developing potential targets for precision therapy. This observational study charac-terised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leucocyte populations in peripheral circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lympho-cytopenia and specific loss of cytotoxic CD8 + lymphocytes were associated with severe COVID-19 and requirement for intensive care in both non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia restricted to classical CD14 Hi CD16 À monocytes was specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Increased expression of inflammatory markers reminiscent of the type 1 interferon pathway (IL6, IL8, CCL2, INFB1) underlaid the immunophenotype associated with T2D. These immunophenotypic and hyperinflammatory changes may contribute to increased voracity of COVID-19 in T2D. These findings allow precise identification of T2D patients with severe COVID-19 as well as provide evidence that the type 1 interferon pathway may be an actionable therapeutic target for future studies