[ChatGPT in clinical practice: prospects and challenges]. / ChatGPT en pratique clinique : perspectives et limites.

Virtually unknown to the greater public before November 2022, ChatGPT was made available in open access in Autumn 2022, driving the perspective of artificial intelligence integration to the forefront of daily life. The field of medicine hasn't been left aside, and sparks as much interest as it does questions. Although this tool has considerable potential for use in clinical practice, it, like others, has limitations that need to be clearly understood to avoid misuse. In addition, the legal framework and issues of data confidentiality are currently poorly defined, and clinicians will need to keep a close eye on legislative developments in this area.

Quasiment inconnu avant novembre 2022, la mise à disposition en libre accès de ChatGPT (Chat Generative Pre-trained Transformer) en automne 2022 a permis au grand public d'être exposé pour la première fois à une forme d'intelligence artificielle (IA). La médecine n'a pas échappé à cette révolution technologique qui suscite autant d'intérêt que de questionnements. Bien que doté d'importantes capacités avec de nombreuses perspectives pour une utilisation en pratique clinique, cet outil, comme d'autres, présente des limites qu'il convient de bien comprendre pour éviter un mésusage. Par ailleurs, le cadre légal et les enjeux de confidentialité des données sont pour l'heure mal définis, et le clinicien devra suivre de manière attentive l'évolution de la législation en ce sens.

[The Internal medicine articles that struck us the most in 2021]. / Année 2021 mise en perspective par les internistes hospitaliers.

The year 2021 has seen many breakthroughs in general internal medicine, despite the ongoing COVID-19 pandemic, with multiple implications in our daily clinical practice. From shorter antibiotic treatment duration in community-acquired pneumonia, to new indications for colchicine treatment, without forgetting better targets of hemoglobin for transfusion, questioning of the interest of high dose vitamin D substitution when preventing falls in older patients and finally disappointing hopes for new indications of albumin substitution in cirrhosis, the literature is full of new evidence. Each year, the chief residents of the internal medicine ward in Lausanne university hospital (CHUV) in Switzerland meet up to share their readings: here is a selection of ten articles, chosen, summarized, and commented for you.

L'année 2021, malgré la pandémie de Covid-19, a vu de nombreux progrès en médecine interne générale, avec de multiples implications pour notre pratique quotidienne. D'une durée diminuée d'antibiothérapie pour le traitement de la pneumonie communautaire à de nouvelles indications au traitement de colchicine, en passant par des précisions sur les cibles de transfusion érythrocytaire, ainsi qu'une remise en question de l'intérêt de la vitamine D à haute dose dans la prévention des chutes chez la personne âgée, et pour finir des espoirs déçus de nouvelle indication à la substitution d'albumine dans la cirrhose, les nouveautés abondent dans la littérature. Chaque année, les cheffes et chefs de clinique du Service de médecine interne du CHUV se réunissent pour partager leurs lectures : voici une sélection de dix articles choisis, revus et commentés pour vous.

[Medical informatics in response to COVID-19 The experience of the Service of Internal Medicine at CHUV]. / Informatique médicale en réponse au Covid-19 - L'expérience du Service de médecine interne du CHUV.

Medical informatics played a decisive role in the management of the health crisis linked to COVID-19, in particular for the support of hospital clinical, governance and communication activities. In this article, we present the experience of CHUV's Internal Medicine Service in these three areas, and analyse some critical points of our information system revealed by the crisis. The development, implementation, and maintenance of new IT tools during the crisis is a challenge. The involvement of medical informatics in the decision-making processes of hospitals and the training of healthcare professionals in this field are essential to strengthen the efficiency of information technologies and the innovation of our healthcare systems.

L'informatique médicale a joué un rôle déterminant dans la gestion de la crise sanitaire liée au Covid-19, notamment pour le support des activités cliniques hospitalières, de gouvernance et de communication. Nous exposons dans cet article l'expérience vécue au sein du Service de médecine interne du CHUV dans ces trois domaines et analysons certains points critiques de notre système d'information révélés par la situation de crise. Le développement, l'implémentation et la maintenance de nouveaux outils informatiques durant la crise constituent un réel défi. L'implication de l'informatique médicale au cœur des processus décisionnels des hôpitaux et la formation des professionnels de santé dans ce domaine sont essentielles pour renforcer l'efficience des technologies de l'information et l'innovation de nos systèmes de santé.

[Computerized clinical decision support for medication in the electronic health record]. / Aide à la prescription médicamenteuse grâce au dossier médical électronique.

Medication prescribing is a critical feature in the electronic health record (EHR). Computerized Clinical Decision Support (CCDS) for medication prescribing has the potential to improve quality of care, patient safety and reduce cost. However, its development, implementation, and maintenance in the clinical environment, are major challenges. We describe the basics of the CCDS in medication prescribing, the acquired experience of the last years at the Lausanne University Hospital (CHUV), and we expose the perspectives and future challenges in this domain.

La prescription médicamenteuse représente une fonction clé au sein du dossier médical électronique. L'aide à la prescription médicamenteuse, qui peut prendre différentes formes (alertes, sets d'ordres), a le potentiel d'améliorer la qualité, la sécurité et l'économicité des soins. Cependant, son développement, son implémentation dans les services cliniques et sa maintenance représentent des défis majeurs. Nous passons en revue ici les principes de l'aide à la prescription médicamenteuse, l'expérience acquise au CHUV ces dernières années, avant d'exposer les perspectives et défis dans ce domaine.

Association of body temperature with obesity. The CoLaus study.

BACKGROUND AND AIMS: There is conflicting evidence regarding the association between body temperature and obesity. We aimed to assess the associations between body temperature and several adiposity and metabolic markers according to gender and menopausal status in a large population-based sample. METHODS: The data collected between 2009 and 2012 from 4224 participants (mean age 57.3 ± 10.4 years, 2225 women) of the CoLaus study (Lausanne, Switzerland). Body temperature was measured at the tympanic membrane. RESULTS: Mean body temperature was 36.1 ± 0.4, 36.4 ± 0.4 and 36.3 ± 0.4 °C in men, premenopausal, and postmenopausal women, respectively (p < 0.001). In men and postmenopausal women, body temperature was positively and significantly (p < 0.05) associated with body mass index (Spearman correlation coefficients 0.157 and 0.083, respectively), waist (r = 0.163 and r = 0.104), waist to hip ratio (r = 0.187 and r = 0.132), body area (r = 0.094 and r = 0.085), resting heart rate (r = 0.227 and r = 182), glucose (r = 0.104 and r = 0.088) and insulin (r = 0.148 and r = 0.117). Except for body area and BMI in postmenopausal women, all associations remained significant after multivariable adjustment. In premenopausal women, body temperature was positively associated with resting heart rate (r = 0.140) and insulin (r = 0.170), and no significant associations were found after multivariable adjustment. CONCLUSION: Body temperature is strongly associated with obesity markers in men and postmenopausal women. The absence of association in premenopausal women might be due to the influence of the menstrual cycle.

[Visual diagnosis†: between medical education and advances in artificial intelligence]. / Le diagnostic visuel†: au carrefour de la pédagogie médicale et des progrès en intelligence artificielle.

The electrocardiogram, chest x-ray, and skin lesion interpretation are a diagnostic process that applies image analysis. Knowledge and sufficient clinical experience are necessary to achieve expertise in these fields. However, recent advances in medical informatics, particularly in deep learning, are challenging this diagnostic process and physicians' performance. Only a fraction of clinical diagnostic support based on artificial intelligence (AI) has been validated in a clinical environment, limiting its use at the patient's bedside. Gradual AI integration into medical practice will require that the physicians remain able to assess the strengths and limitations of these new algorithms.

La lecture d'un ECG, l'analyse d'une radiographie du thorax ou l'approche d'une lésion dermatologique mettent l'interprétation d'une image au centre de la démarche diagnostique. Elles imposent un apprentissage des bases théoriques nécessaires et une exposition suffisante en milieu clinique. Or, les avancées récentes en informatique médicale, en particulier du deep learning, remettent en question l'approche diagnostique classique, disputant leurs performances aux médecins. Cependant, seul un petit nombre d'études relatives à l'intelligence artificielle sont validées à ce jour dans un contexte clinique, limitant son usage au lit du patient. A l'avenir, l'intelligence artificielle pourra progressivement être introduite dans la pratique médicale, pour autant que les médecins eux-mêmes restent capables d'évaluer la qualité de l'aide au diagnostic proposée par le deep learning.

New gene functions in megakaryopoiesis and platelet formation.

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.

[The electronic patient record - a great opportunity to rethink medical information and its use]. / Dossier patient informatisé ­ belle opportunité de repenser l'information médicale et son utilisation.

Since the early 2000s, the management of information concerning patient care has fundamentally changed. Previously stored in separate medical and nursing paper medical records, patient data are now gathered in a single electronic health record (EHR) thanks to the digitization of our hospitals, whose development and mastery are a major issue in today's health system.

Depuis le début des années 2000, la gestion des informations liées à la prise en charge d'un patient a été profondément modifiée. Autrefois conservées sous la forme d'un dossier médical papier et d'un dossier infirmier distinct, les données du patient ont été rassemblées sous la forme d'un dossier patient informatisé (EHR, electronic health record) par la numérisation progressive de nos hôpitaux. Son développement et sa bonne maîtrise constituent aujourd'hui un sujet capital au sein d'un système de santé.

[2015 highlights in hospital-based internal medicine by chief residents]. / L'année 2015 mise en perspective par les internistes hospitaliers.

The year 2015 gave us many scientific publications, among whom some will have an impact on our daily practice and some will influence our way of considering some well known diseases. Chief residents in the Service of internal medicine of the Lausanne University hospital, gathered like every year, to share their readings together in order to presentyou a small part of the many publications of 2015, which have been considered to have an impact on our future daily practice.

A Machine Learning Application to Classify Patients at Differing Levels of Risk of Opioid Use Disorder: Clinician-Based Validation Study.

Background: Despite restrictive opioid management guidelines, opioid use disorder (OUD) remains a major public health concern. Machine learning (ML) offers a promising avenue for identifying and alerting clinicians about OUD, thus supporting better clinical decision-making regarding treatment. Objective: This study aimed to assess the clinical validity of an ML application designed to identify and alert clinicians of different levels of OUD risk by comparing it to a structured review of medical records by clinicians. Methods: The ML application generated OUD risk alerts on outpatient data for 649,504 patients from 2 medical centers between 2010 and 2013. A random sample of 60 patients was selected from 3 OUD risk level categories (n=180). An OUD risk classification scheme and standardized data extraction tool were developed to evaluate the validity of the alerts. Clinicians independently conducted a systematic and structured review of medical records and reached a consensus on a patient's OUD risk level, which was then compared to the ML application's risk assignments. Results: A total of 78,587 patients without cancer with at least 1 opioid prescription were identified as follows: not high risk (n=50,405, 64.1%), high risk (n=16,636, 21.2%), and suspected OUD or OUD (n=11,546, 14.7%). The sample of 180 patients was representative of the total population in terms of age, sex, and race. The interrater reliability between the ML application and clinicians had a weighted kappa coefficient of 0.62 (95% CI 0.53-0.71), indicating good agreement. Combining the high risk and suspected OUD or OUD categories and using the review of medical records as a gold standard, the ML application had a corrected sensitivity of 56.6% (95% CI 48.7%-64.5%) and a corrected specificity of 94.2% (95% CI 90.3%-98.1%). The positive and negative predictive values were 93.3% (95% CI 88.2%-96.3%) and 60.0% (95% CI 50.4%-68.9%), respectively. Key themes for disagreements between the ML application and clinician reviews were identified. Conclusions: A systematic comparison was conducted between an ML application and clinicians for identifying OUD risk. The ML application generated clinically valid and useful alerts about patients' different OUD risk levels. ML applications hold promise for identifying patients at differing levels of OUD risk and will likely complement traditional rule-based approaches to generating alerts about opioid safety issues.

Overlap between common genetic polymorphisms underpinning kidney traits and cardiovascular disease phenotypes: the CKDGen consortium.

BACKGROUND: Chronic kidney disease is associated with cardiovascular disease. We tested for evidence of a shared genetic basis to these traits. STUDY DESIGN: We conducted 2 targeted analyses. First, we examined whether known single-nucleotide polymorphisms (SNPs) underpinning kidney traits were associated with a series of vascular phenotypes. Additionally, we tested whether vascular SNPs were associated with markers of kidney damage. Significance was set to 1.5×10(-4) (0.05/325 tests). SETTING & PARTICIPANTS: Vascular outcomes were analyzed in participants from the AortaGen (20,634), CARDIoGRAM (86,995), CHARGE Eye (15,358), CHARGE IMT (31,181), ICBP (69,395), and NeuroCHARGE (12,385) consortia. Tests for kidney outcomes were conducted in up to 67,093 participants from the CKDGen consortium. PREDICTOR: We used 19 kidney SNPs and 64 vascular SNPs. OUTCOMES & MEASUREMENTS: Vascular outcomes tested were blood pressure, coronary artery disease, carotid intima-media thickness, pulse wave velocity, retinal venular caliber, and brain white matter lesions. Kidney outcomes were estimated glomerular filtration rate and albuminuria. RESULTS: In general, we found that kidney disease variants were not associated with vascular phenotypes (127 of 133 tests were nonsignificant). The one exception was rs653178 near SH2B3 (SH2B adaptor protein 3), which showed direction-consistent association with systolic (P = 9.3 ×10(-10)) and diastolic (P = 1.6 ×10(-14)) blood pressure and coronary artery disease (P = 2.2 ×10(-6)), all previously reported. Similarly, the 64 SNPs associated with vascular phenotypes were not associated with kidney phenotypes (187 of 192 tests were nonsignificant), with the exception of 2 high-correlated SNPs at the SH2B3 locus (P = 1.06 ×10(-07) and P = 7.05 ×10(-08)). LIMITATIONS: The combined effect size of the SNPs for kidney and vascular outcomes may be too low to detect shared genetic associations. CONCLUSIONS: Overall, although we confirmed one locus (SH2B3) as associated with both kidney and cardiovascular disease, our primary findings suggest that there is little overlap between kidney and cardiovascular disease risk variants in the overall population. The reciprocal risks of kidney and cardiovascular disease may not be genetically mediated, but rather a function of the disease milieu itself.

Association between circulating cytokine levels, diabetes and insulin resistance in a population-based sample (CoLaus study).

OBJECTIVE: The associations between inflammation, diabetes and insulin resistance remain controversial. Hence, we assessed the associations between diabetes, insulin resistance (using HOMA-IR) and metabolic syndrome with the inflammatory markers high-sensitive C-reactive protein (hs-CRP), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). DESIGN: Cross-sectional study. PARTICIPANTS: Two thousand eight hundred and eighty-four men and 3201 women, aged 35-75, participated in this study. METHODS: C-reactive protein was assessed by immunoassay and cytokines by multiplexed flow cytometric assay. In a subgroup of 532 participants, an oral glucose tolerance test (OGTT) was performed to screen for impaired glucose tolerance (IGT). RESULTS: IL-6, TNF-α and hs-CRP were significantly and positively correlated with fasting plasma glucose (FPG), insulin and HOMA-IR. Participants with diabetes had higher IL-6, TNF-α and hs-CRP levels than participants without diabetes; this difference persisted for hs-CRP after multivariate adjustment. Participants with metabolic syndrome had increased IL-6, TNF-α and hs-CRP levels; these differences persisted after multivariate adjustment. Participants in the highest quartile of HOMA-IR had increased IL-6, TNF-α and hs-CRP levels; these differences persisted for TNF-α and hs-CRP after multivariate adjustment. No association was found between IL-1ß levels and all diabetes and insulin resistance markers studied. Finally, participants with IGT had higher hs-CRP levels than participants with a normal OGTT, but this difference disappeared after controlling for body mass index (BMI). CONCLUSION: We found that subjects with diabetes, metabolic syndrome and increased insulin resistance had increased levels of IL6, TNF-α and hs-CRP, while no association was found with IL-1ß. The increased inflammatory state of subjects with IGT is partially explained by increased BMI.

Physical activity and energy expenditure in rheumatoid arthritis patients and matched controls.

OBJECTIVES: To compare daily energy expenditure between RA patients and matched controls, and to explore the relationship between daily energy expenditure or sedentariness and disease-related scores. METHODS: One hundred and ten patients with RA and 440 age- and sex-matched controls were included in this study. Energy expenditure was assessed using the validated physical activity (PA) frequency questionnaire. Disease-related scores included disease activity (DAS-28), functional status (HAQ), pain visual analogue scale (VAS) and fatigue VAS. Total energy expenditure (TEE) and the amount of energy spent in low- (TEE-low), moderate- (TEE-mod) and high-intensity (TEE-high) PAs were calculated. Sedentariness was defined as expending <10% of TEE in TEE-mod or TEE-high activities. Between-group comparisons were computed using conditional logistic regression. The effect of disease-related scores on TEE was investigated using linear regression. RESULTS: TEE was significantly lower for RA patients compared with controls [2392 kcal/day (95% CI 2295, 2490) and 2494 kcal/day (2446, 2543), respectively, P = 0.003]. A significant difference was found between groups in TEE-mod (P = 0.015), but not TEE-low (P = 0.242) and TEE-high (P = 0.146). All disease-related scores were significantly poorer in sedentary compared with active patients. TEE was inversely associated with age (P < 0.001), DAS-28 (P = 0.032) and fatigue VAS (P = 0.029), but not with HAQ and pain VAS. CONCLUSION: Daily energy expenditure is significantly lower in RA patients compared with matched controls, mainly due to less moderate-intensity PAs performed. Disease activity and fatigue are important contributing factors. These points need to be addressed if promoting PA in RA patients is a health goal. Trial registration. ClinicalTrials.gov, http://clinicaltrials.gov, NCT01228812.

Impact of smoking on fertility and age of menopause: a population-based assessment.

BACKGROUND AND AIMS: Studies in patients seeking medically assisted reproduction have shown that smoking reduces fertility, but little information is available in the general population. We assessed the associations between smoking and the number of children, childbearing planning and age at menopause in a representative sample of the population of Lausanne, Switzerland. METHODS: Data from 6711 participants (3530 women, age range 35-75 years) collected between 2003 and 2006 and again in 2009 and 2012. Smoking status, number of offsprings and age of menopause were assessed. RESULTS: Women who currently smoke had significantly less children than former or never smokers: the number of children per women (average±SD) was 1.38±1.05, 1.45±1.07 and 1.576±1.16, respectively (p<0.001). Women who currently smoke had their first child at an earlier age than the others: 26.7±5.2, 27.4±5.4 and 26.9±5.2 years old for current, former and never smokers, respectively, (p=0.01). Similar findings were found for men: number of children per men 1.475±1.16, 1.67±1.13 and 1.55±1.22 for current, former and never smokers, respectively (p<0.001); no difference was found regarding age at the first child. The difference persisted after multivariate adjustment (adjusted for age, body mass index, Caucasian origins, alcohol consumption, caffeinated drinks consumption, educational level, receiving social help and women taking contraceptives) for the age at first child among women. No association was found between Heaviness of Smoking Index and the number of children among current smokers in both genders. Women who smoke had their menopause more than 1 year prior than never-smoking women (48.9±0.2 years compared with 47.8±0.3 years, respectively, p=0.002). CONCLUSIONS: Smoking is associated with an earlier age of having the first child and of menopause among women.

Association between anti-apolipoprotein A-1 antibodies and cardiovascular disease in the general population. Results from the CoLaus study.

We aimed to determine the association between autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) and prevalent cardiovascular (CV) disease (CVD) as well as markers of CV risk in the general population. Cross-sectional data were obtained from 6649 subjects (age 52.6 ± 10.7 years, 47.4 % male) of the population-based CoLaus study. CVD was defined as myocardial infarction, angina pectoris, percutaneous revascularisation or bypass grafting for ischaemic heart disease stroke or transient ischaemic attack, and was assessed according to standardised medical records. Anti-apoA-1 IgG and biological markers were measured by ELISA and conventional automated techniques, respectively. Prevalence of high anti-apoA-1 IgG levels in the general population was 19.9 %. Presence of anti-apoA-1 IgG was significantly associated with CVD [odds ratio 1.34, 95 % confidence interval (1.05-1.70), p=0.018], independently of established CV risk factors (CVRFs) including age, sex, hypertension, smoking, diabetes, low and high-density lipoprotein cholesterol levels. The n=455 (6.8 %) study participants with a history of CVD (secondary prevention subgroup) presented higher median anti-ApoA-1 IgG values compared with subjects without CVD (p=0.029). Among patients in the secondary prevention subgroup, those with positive anti-apoA-1 IgG levels had lower HDL (p=0.002) and magnesium (p=0.001) levels, but increased uric acid and high-sensitivity C-reactive protein levels (p=0.022, and p<0.001, respectively) compared to patients with negative anti-apoA-1 IgG levels. In conclusion, anti-apoA-1 IgG levels are independently associated with CVD in the general population and also related to CV biomarkers in secondary prevention. These findings indicate that anti-apoA-1 IgG may represent a novel CVRF and need further study in prospective cohorts.

Depression with atypical features and increase in obesity, body mass index, waist circumference, and fat mass: a prospective, population-based study.

IMPORTANCE: Depression and obesity are 2 prevalent disorders that have been repeatedly shown to be associated. However, the mechanisms and temporal sequence underlying this association are poorly understood. OBJECTIVE: To determine whether the subtypes of major depressive disorder (MDD; melancholic, atypical, combined, or unspecified) are predictive of adiposity in terms of the incidence of obesity and changes in body mass index (calculated as weight in kilograms divided by height in meters squared), waist circumference, and fat mass. DESIGN, SETTING, AND PARTICIPANTS: This prospective population-based cohort study, CoLaus (Cohorte Lausannoise)/PsyCoLaus (Psychiatric arm of the CoLaus Study), with 5.5 years of follow-up included 3054 randomly selected residents (mean age, 49.7 years; 53.1% were women) of the city of Lausanne, Switzerland (according to the civil register), aged 35 to 66 years in 2003, who accepted the physical and psychiatric baseline and physical follow-up evaluations. EXPOSURES: Depression subtypes according to the DSM-IV. Diagnostic criteria at baseline and follow-up, as well as sociodemographic characteristics, lifestyle (alcohol and tobacco use and physical activity), and medication, were elicited using the semistructured Diagnostic Interview for Genetic Studies. MAIN OUTCOMES AND MEASURES: Changes in body mass index, waist circumference, and fat mass during the follow-up period, in percentage of the baseline value, and the incidence of obesity during the follow-up period among nonobese participants at baseline. Weight, height, waist circumference, and body fat (bioimpedance) were measured at baseline and follow-up by trained field interviewers. RESULTS: Only participants with the atypical subtype of MDD at baseline revealed a higher increase in adiposity during follow-up than participants without MDD. The associations between this MDD subtype and body mass index (ß = 3.19; 95% CI, 1.50-4.88), incidence of obesity (odds ratio, 3.75; 95% CI, 1.24-11.35), waist circumference in both sexes (ß = 2.44; 95% CI, 0.21-4.66), and fat mass in men (ß = 16.36; 95% CI, 4.81-27.92) remained significant after adjustments for a wide range of possible cofounding. CONCLUSIONS AND RELEVANCE: The atypical subtype of MDD is a strong predictor of obesity. This emphasizes the need to identify individuals with this subtype of MDD in both clinical and research settings. Therapeutic measures to diminish the consequences of increased appetite during depressive episodes with atypical features are advocated.

Current genetic data do not improve the prediction of type 2 diabetes mellitus: the CoLaus study.

CONTEXT: Several genetic risk scores to identify asymptomatic subjects at high risk of developing type 2 diabetes mellitus (T2DM) have been proposed, but it is unclear whether they add extra information to risk scores based on clinical and biological data. OBJECTIVE: The objective of the study was to assess the extra clinical value of genetic risk scores in predicting the occurrence of T2DM. DESIGN: This was a prospective study, with a mean follow-up time of 5 yr. SETTING AND SUBJECTS: The study included 2824 nondiabetic participants (1548 women, 52 ± 10 yr). MAIN OUTCOME MEASURE: Six genetic risk scores for T2DM were tested. Four were derived from the literature and two were created combining all (n = 24) or shared (n = 9) single-nucleotide polymorphisms of the previous scores. A previously validated clinic + biological risk score for T2DM was used as reference. RESULTS: Two hundred seven participants (7.3%) developed T2DM during follow-up. On bivariate analysis, no differences were found for all but one genetic score between nondiabetic and diabetic participants. After adjusting for the validated clinic + biological risk score, none of the genetic scores improved discrimination, as assessed by changes in the area under the receiver-operating characteristic curve (range -0.4 to -0.1%), sensitivity (-2.9 to -1.0%), specificity (0.0-0.1%), and positive (-6.6 to +0.7%) and negative (-0.2 to 0.0%) predictive values. Similarly, no improvement in T2DM risk prediction was found: net reclassification index ranging from -5.3 to -1.6% and nonsignificant (P ≥ 0.49) integrated discrimination improvement. CONCLUSIONS: In this study, adding genetic information to a previously validated clinic + biological score does not seem to improve the prediction of T2DM.

Adipocytokines, hepatic and inflammatory biomarkers and incidence of type 2 diabetes. the CoLaus study.

CONTEXT: There is contradictory information regarding the prognostic importance of adipocytokines, hepatic and inflammatory biomarkers on the incidence of type 2 diabetes. The objective was to assess the prognostic relevance of adipocytokine and inflammatory markers (C-reactive protein - CRP; interleukin-1beta - IL-1ß; interleukin-6- IL-6; tumour necrosis factor-α - TNF-α; leptin and adiponectin) and gamma-glutamyl transpeptidase (γGT) on the incidence of type 2 diabetes. METHODS: Prospective, population-based study including 3,842 non-diabetic participants (43.3% men, age range 35 to 75 years), followed for an average of 5.5 years (2003-2008). The endpoint was the occurrence of type 2 diabetes. RESULTS: 208 participants (5.4%, 66 women) developed type 2 diabetes during follow-up. On univariate analysis, participants who developed type 2 diabetes had significantly higher baseline levels of IL-6, CRP, leptin and γGT, and lower levels of adiponectin than participants who remained free of type 2 diabetes. After adjusting for a validated type 2 diabetes risk score, only the associations with adiponectin: Odds Ratio and (95% confidence interval): 0.97 (0.64-1.47), 0.84 (0.55-1.30) and 0.64 (0.40-1.03) for the second, third and forth gender-specific quartiles respectively, remained significant (P-value for trend = 0.05). Adding each marker to a validated type 2 diabetes risk score (including age, family history of type 2 diabetes, height, waist circumference, resting heart rate, presence of hypertension, HDL cholesterol, triglycerides, fasting glucose and serum uric acid) did not improve the area under the ROC or the net reclassification index; similar findings were obtained when the markers were combined, when the markers were used as continuous (log-transformed) variables or when gender-specific quartiles were used. CONCLUSION: Decreased adiponectin levels are associated with an increased risk for incident type 2 diabetes, but they seem to add little information regarding the risk of developing type 2 diabetes to a validated risk score.

Associations between alcohol consumption and selected cytokines in a Swiss population-based sample (CoLaus study).

OBJECTIVE: To assess the associations between alcohol consumption and cytokine levels (interleukin-1beta - IL-1ß; interleukin-6 - IL-6 and tumor necrosis factor-α - TNF-α) in a Caucasian population. METHODS: Population sample of 2884 men and 3201 women aged 35-75. Alcohol consumption was categorized as nondrinkers, low (1-6 drinks/week), moderate (7-13/week) and high (14+/week). RESULTS: No difference in IL-1ß levels was found between alcohol consumption categories. Low and moderate alcohol consumption led to lower IL-6 levels: median (interquartile range) 1.47 (0.70-3.51), 1.41 (0.70-3.32), 1.42 (0.66-3.19) and 1.70 (0.83-4.39) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p<0.01, but this association was no longer significant after multivariate adjustment. Compared to nondrinkers, moderate drinkers had the lowest odds (Odds ratio=0.86 (0.71-1.03)) of being in the highest quartile of IL-6, with a significant (p<0.05) quadratic trend. Low and moderate alcohol consumption led to lower TNF-α levels: 2.92 (1.79-4.63), 2.83 (1.84-4.48), 2.82 (1.76-4.34) and 3.15 (1.91-4.73) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p<0.02, and this difference remained borderline significant (p=0.06) after multivariate adjustment. Moderate drinkers had a lower odds (0.81 [0.68-0.98]) of being in the highest quartile of TNF-α. No specific alcoholic beverage (wine, beer or spirits) effect was found. CONCLUSIONS: Moderate alcohol consumption is associated with lower levels of IL-6 and (to a lesser degree) of TNF-α, irrespective of the type of alcohol consumed. No association was found between IL-1ß levels and alcohol consumption.