Comment on : Zhu et al. Fasting Plasma Glucose at 24–28 Weeks to Screen for Gestational Diabetes Mellitus : New Evidence From China. Diabetes Care 2013; 36:2038–2040

The article by Zhu et al. published inDiabetes Care concludes that a fasting plasma glucose (FPG) at 24–28 weeks’ gestation can be used in low-resource regions as a screening test to identify gestational diabetes mellitus (GDM) in Chinese patients. However, in their experience, a screening protocol using FPG cutoff points of $4.4 and #5.0 mmol/L would fail to identify about 12% of the GDM cases and require a formal oral glucose tolerance test (OGTT) to be performed in about half of the pregnant population. These observations contrast with our findings in a circum-Mediterranean population.peer-reviewe

Lower-extremity amputation as a marker for renal and cardiovascular events and mortality in patients with long standing type 1 diabetes

International audienceAbstractBackgroundWe evaluated the risks of renal and cardiovascular complications, and mortality associated with lower extremity amputation (LEA) in patients with type 1 diabetes.MethodsWe studied two cohorts of people with long standing type 1 diabetes: GENEDIAB (n = 456) and GENESIS (n = 611). Subsets of the cohorts (n = 260, n = 544) were followed for 9 and 5 years, respectively. Outcomes were the incidence of end stage renal disease (ESRD), myocardial infarction, stroke and mortality during follow-up. Analyses were performed in pooled cohorts.ResultsThe prevalence of LEA at baseline was 9.3 % (n = 99). A positive history of LEA was associated with the baseline prevalence of established (OR 4.50, 95 % CI 2.33–8.91, p < 0.0001) and advanced diabetic nephropathy (OR 5.50, 95 % CI 2.89–10.78, p < 0.0001), ESRD (OR 2.86, 95 % CI 1.43–5.50, p = 0.004), myocardial infarction (OR 3.25, 95 % CI 1.68–6.15, p = 0.0006) and stroke (OR 3.88, 95 % CI 1.67–8.72, p = 0.002, adjusted for sex, age, and cohort membership). A positive history of LEA at baseline was associated with the incidence during follow-up of ESRD (HR 2.69, 95 % CI 1.17–6.20, p = 0.02), and myocardial infarction (HR 3.53, 95 % CI 1.79–6.97, p = 0.0001). History of LEA was also associated with increased risk for all-cause (HR 3.55, 95 % CI 2.05–6.16, p < 0.0001), cardiovascular (HR 3.30, 95 % CI 1.36–8.02, p = 0.008), infectious disease (HR 5.18, 95 % CI 1.13–23.84, p = 0.03) and other-cause mortality (HR 2.81, 95 % CI 1.09–7.26, p = 0.03). History of LEA at baseline was associated with a 40 % reduction in the duration of survival in the subset of patients who died during follow-up. Population attributable risk of the history of LEA at baseline for total mortality during follow-up was 0.31.ConclusionsPatients with LEA have a higher risk of ESRD, myocardial infarction and cardiovascular and non-cardiovascular mortality. Our results highlight the importance of LEA as a key-predictor for major vascular events and premature death in type 1 diabetic patients

Les phases d’incision de la vallée de la Marne entre Joinville et Vitry-le-François(Est du bassin parisien / France)

L’article porte sur l’analyse de l’incision de la vallée de la Marne, notamment sur la recherche et l’analyse des stades d’incision entre Joinville et Vitry-le-François, dans la traversée du plateau calcaire du Barrois et la dépression alluviale du Perthois. Le levé de la carte géomorphologique a permis de mettre en évidence sept niveaux d’incision visibles aujourd’hui dans le paysage par des formes de versants et/ou de terrasses. Ces sept niveaux peuvent être regroupés en trois familles de formes dont la construction s’étale sur la période « plio-quaternaire ». L’incision totale est de l’ordre de 200 m. Par ailleurs, un passage de la Marne vers le nord, en direction de la vallée de l’Aisne via les paléo-vallées de la Saulx et de l’Ornain, avait été envisagé par le fossé tectonique de Cousance et par la Forêt de Trois-Fontaines dès la fin du XIXe siècle. Les levés effectués montrent que dès la fin de la période de construction de la première famille de formes, la Marne avait un tracé suivant sa vallée actuelle en amont deSaint-Dizier. Le fossé de Cousancea donc été creusé par le jeu de l’érosion différentielle. L’hypothèse d’un paléo-tracé de la Marne par ce passage paraît donc devoir être abandonnée.The paper focuses on the analysis of the incision of the valley of the Marne, in particular on research and analysis of incision stages between Joinville and Vitry-le-François, where it traverses the Barrois limestone plateau and the alluvial plain of Perthois. Geomorphological mapping of slopes and/or terrace forms has revealed seven incision levels visible today in the landscape. These seven levels can be subdivised into three groups, the construction of which extends across the “Plio-Quaternary” period, with a total amount of incision in the order of 200 m. By the end of the nineteenth century, a northward passage of the Marne, in the direction of the Aisne valley via the palaeovalleys of the Saulx and the Ornain, had been envisaged through the Cousance trough and the « Forêt de Trois Fontaines ». The surveys carried out for this study show that, from the end of the period of construction of the first group of forms, the Marne followed a route along its present valley upstream of Saint-Dizier. The Cousance trough has therefore been cut by the action of differential erosion. The hypothesis of a palaeo-route of the Marne via this passage must therefore be abandoned.Der Artikel handelt von der Analyse der Eintiefung des Marnetals, insbesondere von der Untersuchung und Analyse der Eintiefungsstadien zwischen Joinville und Vitry-le-François im Übergang vom Kalkplateau des Barrois zur Alluvial-depression des Perthois. Die Aufnahme der geomorphologischen Karte hat sieben Eintiefungsniveaus deutlich gemacht, die heute in der Landschaft durch Hang- und Terrassenformen sichtbar sind. Diese sieben Niveaus können in drei Formfamilien gruppiert werden, deren Bildung sich über die Plio-Quartär-Periode erstreckt. Die gesamte Eintiefung beträgt etwa 200 m in der Region. Zudem wurde seit Ende des 19. Jahrhunderts ein Übergang der Marne nach Norden in Richtung des Aisnetals über die Paläotäler der Saulx und des Ornain in Betracht gezogen – durch den tektonischen Graben von Cousance und die Forêt des Trois Fontaines. Die Erhebungen zeigen, dass seit dem Ende der Ausbildungsperiode der ersten Formengeneration die Marne einen Verlauf hatte, der dem aktuellen des Tales flussaufwärts von Saint-Dizier folgt. Der Graben von Cousance wurde also durch das differenzierte Spiel der Erosion eingeschnitten. Die Hypothese von einem alten Verlauf der Marne durch diese Passage muss somit wohl verlassen werden

Les phases d’incision de la vallée de la Marne entre Joinville et Vitry-le-François(Est du bassin parisien / France)

L’article porte sur l’analyse de l’incision de la vallée de la Marne, notamment sur la recherche et l’analyse des stades d’incision entre Joinville et Vitry-le-François, dans la traversée du plateau calcaire du Barrois et la dépression alluviale du Perthois. Le levé de la carte géomorphologique a permis de mettre en évidence sept niveaux d’incision visibles aujourd’hui dans le paysage par des formes de versants et/ou de terrasses. Ces sept niveaux peuvent être regroupés en trois familles de formes dont la construction s’étale sur la période « plio-quaternaire ». L’incision totale est de l’ordre de 200 m. Par ailleurs, un passage de la Marne vers le nord, en direction de la vallée de l’Aisne via les paléo-vallées de la Saulx et de l’Ornain, avait été envisagé par le fossé tectonique de Cousance et par la Forêt de Trois-Fontaines dès la fin du XIXe siècle. Les levés effectués montrent que dès la fin de la période de construction de la première famille de formes, la Marne avait un tracé suivant sa vallée actuelle en amont deSaint-Dizier. Le fossé de Cousancea donc été creusé par le jeu de l’érosion différentielle. L’hypothèse d’un paléo-tracé de la Marne par ce passage paraît donc devoir être abandonnée.The paper focuses on the analysis of the incision of the valley of the Marne, in particular on research and analysis of incision stages between Joinville and Vitry-le-François, where it traverses the Barrois limestone plateau and the alluvial plain of Perthois. Geomorphological mapping of slopes and/or terrace forms has revealed seven incision levels visible today in the landscape. These seven levels can be subdivised into three groups, the construction of which extends across the “Plio-Quaternary” period, with a total amount of incision in the order of 200 m. By the end of the nineteenth century, a northward passage of the Marne, in the direction of the Aisne valley via the palaeovalleys of the Saulx and the Ornain, had been envisaged through the Cousance trough and the « Forêt de Trois Fontaines ». The surveys carried out for this study show that, from the end of the period of construction of the first group of forms, the Marne followed a route along its present valley upstream of Saint-Dizier. The Cousance trough has therefore been cut by the action of differential erosion. The hypothesis of a palaeo-route of the Marne via this passage must therefore be abandoned.Der Artikel handelt von der Analyse der Eintiefung des Marnetals, insbesondere von der Untersuchung und Analyse der Eintiefungsstadien zwischen Joinville und Vitry-le-François im Übergang vom Kalkplateau des Barrois zur Alluvial-depression des Perthois. Die Aufnahme der geomorphologischen Karte hat sieben Eintiefungsniveaus deutlich gemacht, die heute in der Landschaft durch Hang- und Terrassenformen sichtbar sind. Diese sieben Niveaus können in drei Formfamilien gruppiert werden, deren Bildung sich über die Plio-Quartär-Periode erstreckt. Die gesamte Eintiefung beträgt etwa 200 m in der Region. Zudem wurde seit Ende des 19. Jahrhunderts ein Übergang der Marne nach Norden in Richtung des Aisnetals über die Paläotäler der Saulx und des Ornain in Betracht gezogen – durch den tektonischen Graben von Cousance und die Forêt des Trois Fontaines. Die Erhebungen zeigen, dass seit dem Ende der Ausbildungsperiode der ersten Formengeneration die Marne einen Verlauf hatte, der dem aktuellen des Tales flussaufwärts von Saint-Dizier folgt. Der Graben von Cousance wurde also durch das differenzierte Spiel der Erosion eingeschnitten. Die Hypothese von einem alten Verlauf der Marne durch diese Passage muss somit wohl verlassen werden

Associations of microvascular complications with all-cause death in patients with diabetes and COVID-19:the CORONADO, ABCD Covid-19 audit and AMERICADO study groups

AIM: To provide a detailled analysis of the microvascular burden in patients with diabetes hopitalized for COVD‐19. MATERIALS AND METHODS: We analysed data from the French CORONADO initiative and the UK Association of British Clinical Diabetologists (ABCD) COVID‐19 audit, two nationwide multicentre studies, and the AMERICADO, a multicentre study conducted in New York area. We assessed the association between risk of all‐cause death during hospital stay and the following microvascular complications in patients with diabetes hospitalized for COVID‐19: diabetic retinopathy and/or diabetic kidney disease and/or history of diabetic foot ulcer. RESULTS: Among 2951 CORONADO, 3387 ABCD COVID‐19 audit and 9327 AMERICADO participants, microvascular diabetic complications status was ascertained for 1314 (44.5%), 1809 (53.4%) and 7367 (79.0%) patients, respectively: 1010, 1059 and 1800, respectively, had ≥1 severe microvascular complication(s) and 304, 750 and 5567, respectively, were free of any complications. The patients with isolated diabetic kidney disease had an increased risk of all‐cause death during hospital stay: odds ratio [OR] 2.53 (95% confidence interval [CI] 1.66‐3.83), OR 1.24 (95% CI 1.00‐1.56) and OR 1.66 (95% CI 1.40‐1.95) in the CORONADO, the ABCD COVID‐19 national audit and the AMERICADO studies, respectively. After adjustment for age, sex, hypertension and cardiovascular disease (CVD), compared to those without microvascular complications, patients with microvascular complications had an increased risk of all‐cause death during hospital stay in the CORONADO, the ABCD COVID‐19 diabetes national audit and the AMERICADO studies: adjusted OR ((adj)OR) 2.57 (95% CI 1.69‐3.92), (adj)OR 1.22 (95% CI 1.00‐1.52) and (adj)OR 1.33 (95% CI 1.15‐1.53), respectively. In meta‐analysis of the three studies, compared to patients free of complications, those with microvascular complications had an unadjusted OR for all‐cause death during hospital stay of 2.05 (95% CI 1.42‐2.97), which decreased to 1.62 (95% CI 1.19‐2.119) after adjustment for age and sex, and to 1.50 (1.12‐2.02) after hypertension and CVD were further added to the model. CONCLUSION: Microvascular burden is associated with an increased risk of death in patients hospitalized for COVID‐19

Circulating amino acids and the risk of macrovascular, microvascular and mortality outcomes in individuals with type 2 diabetes : results from the ADVANCE trial

Aims/hypotheses We aimed to quantify the association of individual circulating amino acids with macrovascular disease, microvascular disease and all-cause mortality in individuals with type 2 diabetes. Methods We performed a case-cohort study (N = 3587), including 655 macrovascular events, 342 microvascular events (new or worsening nephropathy or retinopathy) and 632 all-cause mortality events during follow-up, in a secondary analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study. For this study, phenylalanine, isoleucine, glutamine, leucine, alanine, tyrosine, histidine and valine were measured in stored plasma samples by proton NMR metabolomics. Hazard ratios were modelled per SD increase in each amino acid. Results In models investigating associations and potential mechanisms, after adjusting for age, sex and randomised treatment, phenylalanine was positively, and histidine inversely, associated with macrovascular disease risk. These associations were attenuated to the null on further adjustment for extended classical risk factors (including eGFR and urinary albumin/creatinine ratio). After adjustment for extended classical risk factors, higher tyrosine and alanine levels were associated with decreased risk of microvascular disease (HR 0.78; 95% CI 0.67, 0.91 and HR 0.86; 95% CI 0.76, 0.98, respectively). Higher leucine (HR 0.79; 95% CI 0.69, 0.90), histidine (HR 0.89; 95% CI 0.81, 0.99) and valine (HR 0.79; 95% CI 0.70, 0.88) levels were associated with lower risk of mortality. Investigating the predictive ability of amino acids, addition of all amino acids to a risk score modestly improved classification of participants for macrovascular (continuous net reclassification index [NRI] +35.5%, p <0.001) and microvascular events (continuous NRI +14.4%, p = 0.012). Conclusions/interpretation We report distinct associations between circulating amino acids and risk of different major complications of diabetes. Low tyrosine appears to be a marker of microvascular risk in individuals with type 2 diabetes independently of fundamental markers of kidney function.Peer reviewe

Circulating amino acids and the risk of macrovascular, microvascular and mortality outcomes in individuals with type 2 diabetes : results from the ADVANCE trial

Aims/hypotheses We aimed to quantify the association of individual circulating amino acids with macrovascular disease, microvascular disease and all-cause mortality in individuals with type 2 diabetes. Methods We performed a case-cohort study (N = 3587), including 655 macrovascular events, 342 microvascular events (new or worsening nephropathy or retinopathy) and 632 all-cause mortality events during follow-up, in a secondary analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study. For this study, phenylalanine, isoleucine, glutamine, leucine, alanine, tyrosine, histidine and valine were measured in stored plasma samples by proton NMR metabolomics. Hazard ratios were modelled per SD increase in each amino acid. Results In models investigating associations and potential mechanisms, after adjusting for age, sex and randomised treatment, phenylalanine was positively, and histidine inversely, associated with macrovascular disease risk. These associations were attenuated to the null on further adjustment for extended classical risk factors (including eGFR and urinary albumin/creatinine ratio). After adjustment for extended classical risk factors, higher tyrosine and alanine levels were associated with decreased risk of microvascular disease (HR 0.78; 95% CI 0.67, 0.91 and HR 0.86; 95% CI 0.76, 0.98, respectively). Higher leucine (HR 0.79; 95% CI 0.69, 0.90), histidine (HR 0.89; 95% CI 0.81, 0.99) and valine (HR 0.79; 95% CI 0.70, 0.88) levels were associated with lower risk of mortality. Investigating the predictive ability of amino acids, addition of all amino acids to a risk score modestly improved classification of participants for macrovascular (continuous net reclassification index [NRI] +35.5%, p <0.001) and microvascular events (continuous NRI +14.4%, p = 0.012). Conclusions/interpretation We report distinct associations between circulating amino acids and risk of different major complications of diabetes. Low tyrosine appears to be a marker of microvascular risk in individuals with type 2 diabetes independently of fundamental markers of kidney function.Peer reviewe

The common-866G > A variant in the promoter of UCP2 is associated with decreased risk of coronary artery disease in type 2 diabetic men

OBJECTIVE-Uncoupling protein 2 (UCP2) is a physiological downregulator of reactive oxygen species generation and plays an antiatherogenic role in the vascular wall. A common variant in the UCP2 promoter (-866G>A) modulates mRNA expression, with increased expression associated with the A allele. We investigated association of this variant with coronary artery disease (CAD) in two cohorts of type 2 diabetic subjects.RESEARCH DESIGN and METHODS-We studied 3,122 subjects from the 6-year prospective Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events, and Ramipril (DIABHYCAR) Study (14.9% of CAD incidence at follow-up). An independent, hospital-based cohort of 335 men, 52% of whom had CAD, was also studied.RESULTS-We observed an inverse association of the A allele with incident cases of CAD in a dominant model (hazard risk 0.88 [95% CI 0.80-0.96]; P = 0.006). Similar results were observed for baseline cases of CAD. Stratification by sex confirmed an allelic association with CAD in men, whereas no association was observed in women. All CAD phenotypes considered-myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), and sudden death-contributed significantly to the association. Results were replicated in a cross-sectional study of an independent cohort (odds ratio 0.47 [95% CI 0.25-0.89]; P = 0.02 for a recessive model).CONCLUSIONS-The A allele of the -866G>A variant of UCP2 was associated with reduced risk of CAD in men with type 2 diabetes in a 6-year prospective study. Decreased risk of myocardial infarction, angina pectoris, CABG, and sudden death contributed individually and significantly to the reduction of CAD risk. This association was independent of other common CAD risk factors.INSERM, Fac Med Xavier Bichat, U695, F-75018 Paris, FranceCochin Hosp, AP HP, Dept Immunol & Diabetol, Paris, FranceUniv São Paulo, Lab Cellular & Mol Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilFed Fac Fdn Med Sci Porto Alegre, Post Grad Program Med Sci, Porto Alegre, RS, BrazilHop La Pitie Salpetriere, Dept Cardiol, AP HP, Paris, FranceUniv Paris 07, Paris, FranceUniv Paris 05, Paris, FranceUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilWeb of Scienc

Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study

We investigated associations of allelic variations in the WFS1 gene with insulin secretion and risk of type 2 diabetes in a general population prospective study.We studied 5,110 unrelated French men and women who participated in the prospective Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. Additional cross-sectional analyses were performed on 4,472 French individuals with type 2 diabetes and 3,065 controls. Three single nucleotide polymorphisms (SNPs) were genotyped: rs10010131, rs1801213/rs7672995 and rs734312.We observed statistically significant associations between the major alleles of the three variants and prevalent type 2 diabetes in the DESIR cohort at baseline. Cox analyses showed an association between the G-allele of rs10010131 and incident type 2 diabetes (HR 1.34, 95% CI 1.08-1.70, p = 0.007). Similar results were observed for the G-allele of rs1801213 and the A-allele of rs734312. the GGA haplotype was associated with an increased risk of diabetes as compared with the ACG haplotype (HR 1.26, 95% CI 1.04-1.42, p = 0.02). We also observed statistically significant associations of the three SNPs with plasma glucose, HbA(1c) levels and insulin secretion at baseline and throughout the study in individuals with type 2 diabetes or at risk of developing diabetes. However, no association was observed in those who remained normoglycaemic at the end of the follow-up. Associations between the three variants and type 2 diabetes were replicated in cross-sectional studies of type 2 diabetic patients in comparison with a non-diabetic control group.The most frequent haplotype at the haplotype block containing the WFS1 gene modulated insulin secretion and was associated with an increased risk of type 2 diabetes.Societe Francophone du Diabete (SFD - Alfediam)Association Diabete Risque Vasculaire (ADRV), FranceCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)INSERMCNAMTSLillyNovartis PharmaSanofi-AventisINSERM (Reseaux en Sante Publique, Interactions entre les determinants de la sante)Association Diabete Risque VasculaireFederation Francaise de CardiologieLa Fondation de FranceALFEDIAMONIVINSArdix MedicalBayer DiagnosticsBecton DickinsonCardionicsMerck SanteNovo NordiskPierre FabreRocheTopconUniv Paris 07, INSERM, Res Unit 695, F-75018 Paris, FranceFed Univ Hlth Sci Porto Alegre, Postgradut Program Hlth Sci, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilAssistance Publ Hop Paris Cochin Hosp, Dept Immunol & Diabetol, Paris, FranceUniv Paris 05, UFR Med, Paris, FranceUniv Paris 07, UFR Med, Paris, FranceAssistance Publ Hop Paris Bichat Hosp, Dept Endocrinol Diabetol & Nutr, Paris, FranceInst Inter Reg Sante IRSA, La Riche, FranceINSERM, U1018, CESP, Ctr Res Epidemiol & Populat Hlth, Villejuif, FranceUniv Paris 11, UMRS 1018, Villejuif, FranceUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilCAPES: 1798-09-0Web of Scienc