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Background De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). Methods and findings Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970–1973 to 2006–2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3–75.5 years; % women = 20.4%–62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41–1.66; p < 0.001) for 16:0, 1.40 (1.33–1.48; p < 0.001) for 16:1n-7, 1.14 (1.05–1.22; p = 0.001) for 18:0, and 1.16 (1.07–1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%–73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94–1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors. Conclusions Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D., Fumiaki Imamura and colleagues investigate the association between concentrations of fatty acid involved in de-novo lipogensis and incidence of Type 2 diabetes., Author summary Why was this study done? De novo lipogenesis (DNL) is a metabolic pathway involved in the endogenous synthesis of specific fatty acids, such as 16:0, 16:1n7, 18:0, and 18:1n9, and it is linked to the pathophysiology of cardiometabolic diseases, including type 2 diabetes (T2D). Circulating or tissue concentrations of these fatty acids have been investigated for the associations with T2D incidence in epidemiological research. However, published studies reported inconsistent associations inconsistently and were subject to publication bias. Summary evidence is not available to date for the associations between these fatty acids and T2D incidence. An integration of available cohort studies would increase statistical power and allow assessment of generalizability, standardization of analytical strategies, and evidence synthesis with the potential publication bias minimized. What did the researchers do and find? As a part of the Fatty Acids and Outcomes Research Consortium (FORCE), we conducted new individual-participant data analyses of 17 cohort studies of a total of 65,225 adults free of T2D at baseline, among whom 15,383 developed incident T2D over up to 20 years of follow-up. The cohort studies analyzed the associations between fatty acids (16:0, 16:1n7, 18:0, and 18:1n9) and the risk of developing T2D with standardized analytic strategy. In pooled analyses, each of the fatty acids was positively associated with a higher risk of developing T2D. The associations were independent of major risk factors for T2D, such as age, sex, race/ethnicity, socioeconomic characteristics, smoking status, physical activity, and obesity. What do these findings mean? The findings provide the first summary evidence to date for the positive relationships of concentrations of the DNL-related fatty acids with a risk of T2D, indicating the strong relevance of DNL and its determinants to the development of T2D. These fatty acids potentially reflect the status of DNL activity, which may be stimulated or suppressed by a combination of carbohydrate intake, alcohol intake, polyunsaturated fatty acid intake, and other lifestyle and clinical factors. Therefore, the current findings indicate the need for investigation into determinants and consequences of elevated concentrations of these fatty acids. Despite several advantages of our individual-level data analysis in this pooling project, the results cannot establish whether elevated concentrations of these fatty acids caused the development of T2D or whether underlying peripheral or hepatic insulin resistance, for example, may elevate both the fatty acid concentrations and the risk of T2D independently.

AimWhile serum fructosamine may be a good marker of glucose control in pregnant women with diabetes, its relationship with macrosomia is still uncertain.MethodsIn 130 hyperglycaemic women with singleton pregnancies (117 gestational diabetes mellitus, 13 pregestational diabetes), serum fructosamine and HbA1c levels were measured at 25 ± 7 weeks of gestation. Levels in mothers of infants with and without macrosomic newborns (birth weight > 4000 g and/or large-for-gestational-age birth weight > 90th percentile) were compared using logistic regression analysis adjusted for macrosomia risk factors.ResultsThese 130 pregnant women were 33 ± 5 years old; their BMI before pregnancy was 27.7 ± 6.9 kg/m2, and they gained 7.5 ± 5.1 kg during the first 6 months of gestation. Glucose control was good according to HbA1c levels (5.3 ± 0.3%; 34 ± 2 mmol/mol), yet 17/130 (13%) newborns had macrosomia: 3900 ± 227 g vs 3057 ± 512 g (P < 0.001) in the others. These mothers were older and had higher parity, whereas their BMI scores before pregnancy and gestational weight gains did not differ. Fructosamine levels were also higher at 221 ± 40 μmol/L vs 192 ± 22 μmol/l (P < 0.001), respectively, and remained significant even after adjusting for maternal age, BMI, parity, type of diabetes, antecedents of macrosomia and excessive gestational weight gain. By contrast, HbA1c did not differ between the two groups. In fact, nearly two-thirds (64.7%) of the mothers of macrosomic newborns had fructosamine levels > 200 μmol/l vs 31.9% of mothers with non-macrosomic newborns (P < 0.05).ConclusionHigh fructosamine levels are associated with macrosomia in the newborns of well-controlled hyperglycaemic pregnant women.

Resume La glycation est un processus physiologique accru par l’hyperglycemie chronique. En cas de diabete, la glycation et l’oxydation induisent la formation de produits de la glycation avancee (Advanced Glycation End-products, AGEs), deleteres pour les tissus. Du fait de leurs proprietes optiques, il est possible de mesurer l’autofluorescence cutanee (AF), correlee aux concentrations tissulaires des AGEs. Cette mesure est de realisation facile, et non invasive. L’AF est un marqueur de la memoire metabolique, associe aux valeurs anciennes de l’HbA1c. Cependant, l’âge, la fonction renale et l’heredite influencent les valeurs d’AF. Elle est associee aux complications micro- et macroangiopathiques du diabete quel que soit leur type. En definitive, l’AF pourrait etre utilisee comme marqueur predictif precoce des complications du diabete. Meme si son interpretation reste delicate, l’utilisation de l’AF en pratique courante serait possible afin d’optimiser la prise en charge du patient vers une medecine personnalisee.

We were interested in the comment from Cosson et al. (1) on our recent report about high skin autofluorescence (sAF) in hyperglycemic mothers of large-for-gestational-age (LGA) newborns (2). Several reasons can explain why Cosson et al., and previously de Ranitz-Greven et al. (3), failed to detect a relationship between sAF and macrosomia. The first explanation is the low number of participants, 100 in de Ranitz-Greven et al. (3) and 148 in Cosson et al. (1), which can lead to an underpowered study and a lack of statistical power, versus 343 …

Background Although many type 2 diabetes mellitus (T2DM) risk factors have been identified, little is known regarding their contributions to the diabetes burden at the population level. Methods The study included 72 655 French women from the Etude Epidemiologique de Femmes de la Mutuelle Generale de l'Education Nationale (E3N) prospective cohort followed between 1993 and 2011. Cox multivariable models including the main T2DM risk factors (metabolic, dietary, clinical, socioeconomic and hormonal) and a healthy lifestyle index combining five characteristics (smoking, body mass index [BMI], alcohol consumption, fruit and vegetable consumption, and physical activity) were used to estimate hazard ratios and population attributable fractions (PAFs) for T2DM. Results In multivariate models, factors with the strongest effect on T2DM risk were, in decreasing order, BMI ≥ 30 kg/m2 (PAF = 43%; 95% confidence interval [CI] 37-47), high adherence to a Western dietary pattern (PAF = 30%; 95% CI 20-40), hypertension (PAF = 26%; 95% CI 20-32), an acidogenic diet (PAF = 24%; 95% CI 16-32), a family history of diabetes (PAF = 20%; 95% CI 17-22), and, with a negative correlation, moderate alcohol consumption (PAF-19%; 95% CI -34, -4). The PAF for an unhealthy lifestyle was 57% (95% CI 50-63). Conclusions We have been able to sort out and quantify the effect of various dietary and biological T2DM risk factors simultaneously in a single population, and to highlight the importance of a healthy lifestyle for primary prevention: more than half the T2DM cases could have been prevented through a healthier lifestyle.

International audience; AimsTo identify the most important determinants associated with not developing Type 2 diabetes in women considered to be at very high risk.MethodsBetween 1995 and 2014, we followed 402 women from the E3N cohort study who were considered to be at very high risk of Type 2 diabetes based on the D.E.S.I.R. score. We then computed a classification and regression tree model to identify, among a large set of risk factors, the top risk factors associated with not having Type 2 diabetes at the end of the follow‐up.ResultsDuring follow‐up, 117 women (29%) were diagnosed with Type 2 diabetes, while 285 (71%) were still free of the disease in 2014. A low Western dietary pattern score was the top characteristic associated with not developing Type 2 diabetes, as only 20% of the women at very high risk in the E3N study with that characteristic developed Type 2 diabetes (compared with 29% overall). In women with a moderate or high Western dietary pattern score, the most important characteristic associated with not developing Type 2 diabetes was a high total dietary antioxidant capacity, as only 26% of these women ultimately developed Type 2 diabetes.ConclusionsWe showed that the top characteristic associated with not developing Type 2 diabetes, despite being at very high risk, was a healthy diet, characterized by limiting Western dietary habits, but with a high intake of antioxidant‐rich foods. This underscores the importance of diet in the prevention of Type 2 diabetes in people at high risk.

Background Advanced glycation end-products play a role in diabetic vascular complications. Their optical properties allow to estimate their accumulation in tissues by measuring the skin autofluorescence (SAF). We searched for an association between SAF and major adverse cardiovascular events (MACE) incidence in subjects with Type 1 Diabetes (T1D) during a 7 year follow-up. Methods During year 2009, 232 subjects with T1D were included. SAF measurement, clinical [age, sex, body mass index (BMI), comorbidities] and biological data (HbA1C, blood lipids, renal parameters) were recorded. MACE (myocardial infarction, stroke, lower extremity amputation or a revascularization procedure) were registered at visits in the center or by phone call to general practitioners until 2016. Results The participants were mainly men (59.5%), 51.5 ± 16.7 years old, with BMI 25.0 ± 4.1 kg/m2, diabetes duration 21.5 ± 13.6 years, HbA1C 7.6 ± 1.1%. LDL cholesterol was 1.04 ± 0.29 g/L, estimated Glomerular Filtration Rates (CKD-EPI): 86.3 ± 26.6 ml/min/1.73 m2. Among these subjects, 25.1% were smokers, 45.3% had arterial hypertension, 15.9% had elevated AER (≥ 30 mg/24 h), and 9.9% subjects had a history of previous MACE. From 2009 to 2016, 22 patients had at least one new MACE: 6 myocardial infarctions, 1 lower limb amputation, 15 revascularization procedures. Their SAF was 2.63 ± 0.73 arbitrary units (AU) vs 2.08 ± 0.54 for other patients (p = 0.002). Using Cox-model, after adjustment for age (as the scale time), sex, diabetes duration, BMI, hypertension, smoking status, albumin excretion rates, statin treatment and a previous history of MACE, higher baseline levels of SAF were significantly associated with an increased risk of MACE during follow-up (HR = 4.13 [1.30–13.07]; p = 0.02 for 1 AU of SAF) and Kaplan–Meier curve follow-up showed significantly more frequent MACE in group with SAF upper the median (p = 0.001). Conclusion A high SAF predicts MACE in patients with T1D. Electronic supplementary material The online version of this article (10.1186/s12933-018-0718-8) contains supplementary material, which is available to authorized users.

BACKGROUND Micronutrients play a key role in type 2 diabetes mellitus (T2DM), but methodological difficulties arise from their collinearity and interdependencies with foods. The aim of the present study was to identify micronutrient dietary patterns in the E3N-EPIC (Etude Epidemiologique aupres de femmes de l'Education Nationale) cohort and to investigate their association with risk of T2DM. METHODS Principal component analysis was used to identify micronutrient patterns among 71 270 women from the E3N-EPIC cohort. Associations between micronutrient patterns and risk of T2DM were quantified by hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazards regression models, adjusted for potential confounders. RESULTS Six micronutrient patterns were identified explaining 78% of the total variance in micronutrient intake. A positive association was found between T2DM and a pattern highly correlated with intake of vitamins B2 and B5 (HR 1.34; 95% CI 1.16-1.56). Similarly, a positive association was found with a pattern characterized by high intakes of vitamin B12 and retinol, and a low intake of vitamin C (HR 1.30; 95% CI 1.15-1.48). An inverse association was observed between T2DM and another two patterns: one correlated with magnesium and vitamin B3 (HR 0.75; 95% CI 0.66-0.86), and the other correlated with manganese intake (HR 0.82; 95% CI 0.72-0.94). CONCLUSIONS The findings of the present study identify micronutrients that have an effect on the risk of T2DM, and enable better understanding of the complexity of the diet when investigating the association between micronutrients and T2DM.

Diabetic retinopathy is a microvascular complication of diabetes that threatens all individuals with diabetes, leading to vision loss or blindness if left untreated. It is frequently associated with diabetic macular edema, which can occur at any point during the development of diabetic retinopathy. The key factors known to lead to its development include hyperglycemia, hypertension, and the duration of diabetes. Though the diet is important in the development of diabetes, its role in diabetic retinopathy has not been clearly identified. In this systematic review, we aimed to identify, summarize and interpret the literature on the association between the diet and dietary intakes of specific foods, nutrients, and food groups, and the risk of diabetic retinopathy. We searched PubMed and Web of Science for English-language studies evaluating the association between the dietary intake of individual foods, macro or micronutrients, dietary supplements, and dietary patterns and their association with retinopathy or macular edema. After reviewing potentially relevant abstracts and, when necessary, full texts, we identified 27 relevant studies. Identified studies investigated intakes of fruit, vegetables, fish, milk, carbohydrates, fibre, fat, protein, salt, potassium, vitamins C, D, and E, carotenoids, dietary supplements, green tea and alcohol. Studies suggest that adherence to the Mediterranean diet and high fruit, vegetable and fish intake may protect against the development of diabetic retinopathy, although the evidence is limited. Studies concerning other aspects of the diet are not in agreement. The role of the diet in the development of diabetic retinopathy is an area that warrants more attention.

International audience; BACKGROUND:Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed.OBJECTIVE:We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies.METHODS:Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants.RESULTS:There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides.CONCLUSIONS:Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes.

We aimed to determine whether adherence to the Australian dietary guidelines and an index of healthy behavior was associated with a lower risk of type 2 diabetes (T2D) and to provide estimates of the proportion of preventable cases. Participants of the AusDiab cohort study were followed for 12 years (n = 6242), starting from May 1999, during which T2D cases were identified. The associations between T2D risk and a score of adherence to the dietary guidelines, its components, and a score of adherence to an index of healthy behaviors, (which included smoking, recreational physical activity, waist circumference and adherence to the dietary guidelines), were estimated using Cox proportional hazards ratios (HR) and 95% confidence intervals. The proportion of preventable cases was estimated using the population attributable fraction (PAF). Strong adherence to the dietary guidelines was not associated with T2D risk (HR = 0.64 [95% CI 0.39–1.06]), unless moderate alcohol consumption was considered as beneficial instead of no alcohol consumption (HR = 0.59 [0.36–0.96]). However, strong adherence to the guidelines regarding fruit and dairy intake were both associated with decreased risk of T2D (HR = 0.68 [0.51–0.91]; 0.56 [0.38–0.84], respectively) and could have prevented 23–37% of cases (PAF = 23.3% [7.3–38.2]; 37.1% [14.6–56.0], respectively). Strong adherence to the index of healthy behaviors was associated with decreased risk of T2D (HR = 0.30 [0.17–0.51]) and estimated to prevent almost 60% of T2D (PAF = 59.4% [34.3–76.6]). More than half of T2D cases could be preventable in Australia through modifying health behavior. These results could serve as a basis for prevention programs based on lifestyle modification.

International audience; The incidence of type 2 diabetes (T2D) is steadily rising worldwide since the past 30 years. There is increasing interest in understanding the contribution of exposure to endocrine disrupting chemicals (EDCs) to T2D trend. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are stable, persistent, and bioaccumulative synthetic compounds, suspected to act as EDCs and for which the diet is the main route of exposure. We investigated associations between estimated dietary exposure to PFOS and PFOA and the risk of T2D in the large E3N prospective cohort study. Among 71 270 women included in this study, 2680 cases of incident type 2 diabetes were validated during follow-up (1993-2012). Dietary exposure was estimated combining dietary consumption data collected in E3N and food contamination data provided by ANSES in the 2nd French Total Diet Study. The estimated mean dietary exposure to PFOS and PFOA was 0.50 ng/kg (body weight)/day and 0.86 ng/kg body weight/day respectively. An inverse U-shape association was found when considering PFOA and T2D: women in the 4th, 5th, and 6th decile groups had a HR [95%CI] of 1.21 [1.06-1.46], 1.35 [1.15-1.59], and 1.33 [1.05-1.41], respectively, when compared to women of the 1st decile group, while the other decile groups were not associated to the risk of T2D. The positive association had the strongest effect size for non-obese women (body mass index (BMI)

Summary Background Iodine is an essential micronutrient needed for the production of thyroid hormones. Consequently, iodine insufficient and excessive intakes are associated with thyroid disorders. Despite the increase in diabetes prevalence worldwide and the close relationship between thyroid function and the risk of diabetes, the relationship between iodine intake and diabetes has been overlooked. The objective of the present study is to investigate the link between iodine intake and the risk of type 2 diabetes. Methods Cox proportional hazards regression models adjusted on potential confounders were used to calculate the hazard ratios and 95% confidence intervals for the associations between dietary iodine intake and type 2 diabetes risk among 71,264 women of the E3N-EPIC cohort. Results The average iodine intake in the study population was 155.6 μg/day (±47.1 μg/day). After adjusting for the main risk factors for diabetes, for hypo/hyperthyroidism, as well as for phosphorus intakes and consumption of dairy products and seafood, the hazard ratios (95% CI) for type 2 diabetes of women in the 4th (160.7–190.5 μg/day) and 5th (190.6–596.8 μg/day) quintiles groups of iodine intake were 1.27 (1.10–1.47) and 1.28 (1.07–1.53), respectively, compared to women with iodine intake below the 1st quintile (29.3–116.9 μg/day). Conclusion This is the first study to investigate the relationship between dietary iodine intake and the risk of developing type 2 diabetes. More studies are warranted to further investigate the health effects of chronic high iodine intake, and in particular to investigate the biological mechanisms that underlie the association between iodine intake and type 2 diabetes.

Background We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D). Methods and findings Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance–weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73–0.87); of 17:0, 0.65 (0.59–0.72); of t16:1n7, 0.82 (0.70–0.96); and of their sum, 0.71 (0.63–0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist. Conclusions In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D., Fumiaki Imamura and colleagues reveal a correlation between higher levels of circulating and adipose odd-chain fatty and trans-palmitoleic acids and lower risk of developing diabetes., Author summary Why was this study done? Effects of dairy fat on type 2 diabetes (T2D) are not well established. While dairy fat contains palmitic acid that could increase risk of T2D, it also contains several other types of fatty acids and further reflects specific foods, such as cheese or yogurt, that could reduce risk. Most prior studies of dairy foods and T2D have relied on self-reported dietary questionnaires, which may have errors or bias in memory as well as challenges in assessing less apparent sources of dairy fat such as in creams, sauces, cheeses, and cooking fats in mixed meals and prepared foods. Circulating and tissue biomarker concentrations of odd-chain saturated fats (15:0, 17:0) and natural ruminant trans-fats (trans-16:1n7) at least partly reflect dairy fat consumption, help capture multiple dietary sources without relying on memory or subjective reporting, and reflect a complementary approach to investigate associations with T2D. A consortium strategy combining all available studies maximises statistical power and generalizability, allows standardised analytical approaches and methods including of key population subgroups, and minimises potential for publication bias. What did the researchers do and find? We conducted a consortium project to pool new participant-level analyses of 16 cohort studies as part of the Fatty Acids and Outcomes Research Consortium (FORCE), including a total of 63,682 adults free of T2D at baseline, among whom 15,158 developed incident T2D over up to 20 years of follow-up. Participating studies conducted standardised analysis of the prospective associations between fatty acid biomarkers (15:0, 17:0, trans-16:1n7, and their sum) and the risk of developing T2D. Pooling all studies, each of the biomarkers and their sum were associated with lower risk of developing T2D, independently of major risk factors for T2D, including age, sex, race/ethnicity, socioeconomic status, physical activity, and obesity. For example, for the sum of these biomarkers, participants with higher levels experienced 29% (95% CI 21% to 37%) lower risk of T2D than adults with lower levels, comparing between the midpoints of the top fifth and the bottom fifth of concentrations. What do these findings mean? Higher circulating and tissue concentrations of odd-chain saturated fats and a natural ruminant trans-fat are associated with lower risk of T2D. While these biomarkers are known to reflect dairy fat consumption, their levels could also be influenced by other unknown factors. The findings support the need for investigation of determinants of levels of these fatty acids as well as health effects of dairy fat in interventional studies. Despite the several advantages of evaluating fatty acid biomarkers, the results cannot distinguish between different types of dairy foods (e.g., milk, cheese, yogurt, others), which could have differential effects. The findings provide the strongest evidence to date for relationships of these fatty acid biomarkers with T2D, informing the potential health effects and corresponding dietary recommendations for consumption of selected dairy products.

Micronutrients play a key role in type 2 diabetes mellitus (T2DM), but methodological difficulties arise from their collinearity and interdependencies with foods. The aim of the present study was to identify micronutrient dietary patterns in the E3N-EPIC (Etude Epidémiologique auprès de femmes de l'Education Nationale) cohort and to investigate their association with risk of T2DM.Principal component analysis was used to identify micronutrient patterns among 71 270 women from the E3N-EPIC cohort. Associations between micronutrient patterns and risk of T2DM were quantified by hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazards regression models, adjusted for potential confounders.Six micronutrient patterns were identified explaining 78% of the total variance in micronutrient intake. A positive association was found between T2DM and a pattern highly correlated with intake of vitamins BThe findings of the present study identify micronutrients that have an effect on the risk of T2DM, and enable better understanding of the complexity of the diet when investigating the association between micronutrients and T2DM.

Aim To determine whether skin autofluorescence can help to detect those who have previously had abnormal glucose levels among women referred for diabetes during pregnancy. Methods Using an advanced glycation end product reader (AGE Readertm; DiagnOptics BV, Groningen, the Netherlands), we measured forearm skin autofluorescence at 24–30 weeks of gestation in all women who were referred to our Nutrition Diabetology unit for diabetes during pregnancy. Results The study included 230 women (200 with gestational diabetes and 30 with pre-gestational diabetes, of whom 21 had Type 1 and nine had Type 2 diabetes) and a reference group of 22 normoglycaemic non-pregnant women. Skin autofluorescence was significantly higher in women with pre-gestational diabetes (1.97 ± 0.44 arbitary units) compared with gestational diabetes (1.77 ± 0.32 arbitary units; P = 0.003) and lower in the reference group (1.60 ± 0.32 arbitary units; P = 0.009 vs all pregnant women). Among women with gestational diabetes, 71 had a history of hyperglycaemia (i.e. gestational diabetes or macrosomia in a previous pregnancy or discovery of diabetes before 24th gestational week in the present pregnancy). These women had higher levels of skin autofluorescence (1.83 ± 0.35 arbitary units) than women with gestational diabetes without previous history of hyperglycaemia (1.73 ± 0.30 arbitary units; P = 0.04, non-significant, adjusted for age). Skin autofluorescence increased with the number of criteria present for previous hyperglycaemia (P for trend = 0.008) and was significantly associated with having two or three criteria for hyperglycaemia after adjusting for age (P = 0.02). Conclusions Skin autofluorescence could reflect previous long-term hyperglycaemia in pregnant women, and could therefore be a marker of metabolic memory.

Background: Circulating saturated fatty acids are biomarkers of diet and metabolism that may influence the pathogenesis of diabetes. Unlike palmitic acid (16:0), which has been extensively studied, little is known of the relationship of very long-chain saturated fatty acids (VLSFAs), with 20 carbons or more, to diabetes risk. Objective: To investigate the associations of circulating levels of VLSFA with incident diabetes. Methods: A meta-analysis was conducted within a consortium of prospective (cohort or nested case-control) studies having circulating measures of one or more VLSFAs, including arachidic acid (20:0), behenic acid (22:0) and lignoceric acid (24:0). Standardized analysis was conducted in each study using pre-specified models, exposures, outcomes, and covariates. Study-specific estimates were pooled using fixed effects meta-analysis. Results: Current findings were based on 9 participating studies, including 46,549 total participants and 13,750 incident diabetes. In multivariable-adjusted analyses, higher levels of all 3 VLSFAs were associated with lower risk of incident diabetes. Pooled RRs (95% CI) per interquintile range were 0.80 (0.71-0.90) for 20:0; 0.83 (0.76-0.91) for 22:0; and 0.70 (0.63-0.79) for 24:0, after adjustment for demographics, lifestyle factors and clinical conditions. Additional adjustments for circulating palmitic acid and triglyceride levels moved the RRs toward the null (illustrated for 24:0, in model 3 of the Figure ). Conclusions: Based on meta-analysis of results from several studies around the world, biomarker levels of VLSFA are associated with lower risk of incident diabetes, potentially mediated by effects on circulating triglycerides and 16:0.

BACKGROUND The deposit of advanced glycation end-products is involved in diabetic complications. It can be evaluated by measuring the skin autofluorescence (sAF). We searched whether sAF progressed over 4 years in type 1 diabetes and analysed its relationship with the development of nephropathy. METHODS Two measurements of skin autofluorescence (sAF) were completed on 154 patients during years 2009 and 2013. Baseline factors associated with the progression of sAF were analysed by multivariate regression analysis. The relations among sAF progression, microalbuminuria, and impaired estimated glomerular filtration rate (eGFR) were analysed by logistic regression analysis. RESULTS The patients were 51 ± 16 years old, with duration of diabetes of 23 ± 13 years, HbA1c: 7.7 ± 1.0%, 20.7% were treated by continuous subcutaneous insulin infusion (CSII). The sAF progressed by +18.1% over 4 years. Two interacting (P = .04) variables were associated with the later progression of sAF: mildly impaired eGFR and treatment by CSII. The patients with mildly impaired eGFR had the highest progression of sAF (+11.5% P = .01). Continuous subcutaneous insulin infusion was associated with a reduced progression of sAF in patients without kidney impairment (s = -7.2%, P = .01). A +10% progression of sAF during the follow-up was associated with more microalbuminuria: OR = 1.45, P = .02, and more mildly impaired eGFR (

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since jeudi 30 mars 2017

Objectives Advanced glycation end-products (AGEs) are involved in diabetic retinopathy (DR). Their accumulation in tissues can be analyzed by measuring the skin autofluorescence (sAF). We hypothesized that renal insufficiency, another cause of high sAF, may disturb the relation between sAF and DR. Research Design and Methods We measured sAF with an AGE-Reader in 444 patients with type 2 diabetes (T2D), and we analyzed their retinal status. The associations of sAF with DR, and interaction with renal insufficiency were estimated by multivariate logistic regression analysis. Results Mean age was 62 years (standard deviation (SD) 10 years), diabetes duration 13 (9) years and mean HbA1C 8.9% (1.8). The prevalence of DR was 21.4% and increased with age, diabetes duration, arterial hypertension, renal parameters (serum creatinine and albumin excretion rates), and sAF. The prevalence of macular edema (ME) was 8.6% and increased with the duration of diabetes, but not with sAF (p = 0.11). There was a significant interaction between renal insufficiency and sAF for the relation with DR or ME (p = 0.02). For the 83% patients without renal insufficiency (estimated GFR > 60 mL/min/1.73 m2), sAF was related to DR or ME after multivariate adjustment: OR 1.87 (1.09–3.19). The 17% patients with renal insufficiency had the highest rates of DR or ME (38.6%) and the highest sAF, unrelated to each other. Conclusions In T2D patients with renal insufficiency, the high sAF does not relate to retinopathy, which should be systematically searched due to its high frequency. For other patients, a high sAF argues for DR screening.

Background We aimed to analyze the relationships between skin autofluorescence (SAF) and incident macrovascular events and renal impairment after 4 years of follow-up in patients with type 1 diabetes (T1D). Methods Two hundred and forty-three patients (51.2 ± 16.7 years old) with T1D participated. SAF was measured by AGE-Reader-TM at inclusion. Macrovascular events (MVE), estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER) were recorded then and 4 years later. Multivariate logistic regression was used to analyze the relationships between SAF and incident MVE and renal profile 4 years later. Results Patients with incident MVE had a higher SAF (p = 0.003). SAF predicted incident MVE after adjustment for age, sex, body mass index, tobacco, diabetes duration, hypertension, HbA1c, AER, eGFR (OR 4.84 [95 % CI 1.31–17.89], p = 0.018). However, this relation was no longer significant after adjustment for history of MVE. An inverse relation was found between SAF and incident eGFR (p = 0.0001). Patients with incident eGFR

We were interested by the article from Kelly et al. (1), who reported that markers of subclinical renal damage predicted later preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM). Although the best predictor was neutrophil gelatinase-associated lipocalin, our interest focused on the higher estimated glomerular filtration rates (determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) before preeclampsia. Hyperfiltration is considered an important early step of diabetic nephropathy, but it should be noted that glomerular filtration rates are not properly predicted in pregnancy, by any formula, including the CKD-EPI (2). Much more common than T1DM, gestational diabetes mellitus (GDM) also …

Introduction Les produits de glycation avancee (AGEs) jouent un role dans le developpement de la microangiopathie diabetique. L'objectif de notre etude etait d'analyser l'association entre l'accumulation des AGEs estimee par la mesure de l'autofluorescence cutanee et la prevalence de la retinopathie diabetique chez les patients diabetiques de type 2. Materiels et Methodes Nous avons mesure l'autofluorescence cutanee chez 444 patients hospitalises pour diabete de type 2 desequilibre. La retinopathie diabetique a ete classee par un ophtalmologiste (de ville ou hospitalier) sur un fond d'oeil en les classes suivantes : absente, non proliferante legere, moderee a severe, proliferante ou compliquee. et presence ou non d'un œdeme maculaire. L'association entre autofluorescence cutanee et reti-nopathie diabetique a ete etudiee grâce a un modele de regression logistique multivariee ajustee sur la duree du diabete, l'HbA 1c et l'hypertension arterielle. Resultats Les 444 patients (59,3 % hommes) etaient âges de 62 ± 10 ans, la duree du diabete etait de 13,4 ± 9,6 ans, leur HbA 1c a 8,9 ± 1,8 %, 67,3 % etaient hypertendus et 63,7 % etaient traites par insuline. La retinopathie etait presente chez 21,4 % des patients : 13,5 % non proliferantes, 7,8 % proliferantes. La retinopathie diabetique etait significativement associee a l'âge ( p = 0,03), la duree du diabete ( p p = 0,04) et au debit de filtration glomerulaire (DFG) estime par EPI-CKD ( p p = 0,02). L'autofluorescence etait associee a l'âge ( p p = 0,0004), a l'HbA 1c ( p = 0,006) et a l'hypertension arterielle ( p = 0,02). L'autofluorescence cutanee chez les patients sans retinopathie diabe-tique etait en moyenne de 2,47 (ET : 0,62) contre 2,67 (ET : 0,53) chez les patients atteints de retinopathie diabetique (dont oedeme maculaire) OR = 1,65 IC 95 % [1,16 ; 2,35], p = 0,005. La difference restait significative apres ajuste-ment sur la duree du diabete, l'HbA 1c et l'hypertension arterielle : OR = 1,50 ; IC 95 % [1,03 ; 2,20], p = 0,036. Conclusions Chez les patients diabetiques de type 2, l'autofluorescence cutanee est associee a la presence d'une retinopathie diabetique, et ce meme apres ajustement sur la duree du diabete, l'HbA 1c et l'hypertension arterielle.

Background Advanced glycation end products are involved in the vascular complications of diabetes, in chronic kidney disease, and in the aging process. Their accumulation in the elderly people, as reflected by skin autofluorescence (sAF), may be a marker of metabolic memory. We aimed to examine the association of sAF with glycemic and renal status 10 years earlier in older persons. Methods In retrospective cohort study, 328 elderly community dwellers aged of 75 years and over had sAF measurement 10 years after their inclusion in the Three-City cohort. Fasting plasma glucose and serum creatinine were measured at baseline and at 10-year follow-up. In 125 participants, HbA1c was available at these two times. Associations between sAF and the glycemic and renal status 10 years before were analyzed by multivariate linear regression adjusted for age, sex, hypertension, body mass index, hypertriglyceridemia, and smoking. Results Participants were 82.4 (standard deviation = 4.1) years on average, and their mean sAF was 2.8 (standard deviation = 0.7) arbitrary units (AU). After adjustment, sAF was higher in participants with long-standing diabetes (+0.38 AU, p = .01) or chronic kidney disease (+0.29 AU, p = .02) compared with healthy participants. sAF was related to fasting plasma glucose (+1 mmol/L associated with +0.08 AU, p = .01) and HbA1c (+1% associated with +0.15 AU, p = .03) 10 years earlier, but not to the current fasting plasma glucose (p = .82) and HbA1c (p = .32). sAF was also related to the distal and current estimated glomerular filtration rates (p = .002 and .004, respectively). Conclusions sAF reflects glycemic and renal status 10 years before, supporting its value as a marker of metabolic memory in the elderly people.

Introduction La neuropathie peripherique est une complication frequente du diabete de type 1 (DT1) ; il est souhaitable de pouvoir identifier plus precocement les sujets a risque. L'autofluorescence (AF) cutanee, qui reflete le depot tissulaire des produits de glycation avancee, permet-elle de predire l'apparition de symptome de neuropathie ? Patients et methodes Deux cent quarante-trois patients DT1 ont beneficie en 2009 d'une mesure d'AF cutanee (AGE-Reader (Diagnoptics) resultats exprimes en Unites Arbitraires). En 2013, ils ont ete revus pour la recherche de l'apparition de nouveaux signes cliniques de neuropathie : douleurs neuropathiques, baisse de sensibilite superficielle, maux perforants, mesure de la sensibilite vibratoire (neuroesthesiometrie, Owen Munford). Resultats A l'inclusion en 2009 : 58,8 % d'hommes, âge 51 ± 16 ans, duree de diabete 21 ± 13 ans, AF : 2,13 ± 0,57 UA. Quatre ans plus tard : 29 perdus de vue, 6 deces (AF respectives en 2009 : 2,13 ± 0,62, AF : 2,23 ± 0,80) ; 214 patients sont revus dont 150 ont une mesure de neuro-esthesiometrie. Les scores DN4 de 2013 sont correles aux AF de 2009. Trente patients ont developpe des signes cliniques de neuropathie entre 2009 et 2013 : 4 des douleurs neuropathiques, 15 une baisse de sensibilite superficielle, 9 des maux perforants. Les patients qui ont vu apparaitre des signes de neuropathie differaient en 2009 des autres patients par leur âge (+12 ans, p p p =0,12), la presence d'une maladie renale chronique (54 % vs 18 %, p vs 2,08 ± 0,54 ( p p =0,02), la taille ( p =0,015) et l'AF ( p =0,002). Conclusion L'autofluorescence cutanee mesuree 4 ans plus tot semble etre un element predictif de l'apparition d'une neuropathie peripherique au cours du DT1. Declaration d’interet Les auteurs declarent ne pas avoir d'interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

Introduction L'autofluorescence cutanee (AF), reflet de l'accumulation tissulaire des produits avances de la glycation, est associee au risque d'evenements cardiovasculaires chez le diabetique de type 2. Nous avons recherche si cette relation existait au cours du diabete de type 1 (DT1) en tenant compte du facteur predicteur majeur qu'est la maladie renale chronique. Patients et methodes Les donnees cliniques et biologiques de sujets avec un DT1 ont ete colligees en 2009 et 2013. L'AF a ete mesuree a l'inclusion avec l'AGE ReaderTM (DiagnOpticsTechnologies B.V., Groningen, Netherlands), exprimee en unites arbitraires (UA). La presence de macroangiopathies (MA) ete recherchee a l'inclusion puis apres 4 ans. Analyse statistique avec le logiciel SPSS (Anova, regression logistique). Resultats 243 sujets ont ete inclus en 2009 (âge moyen: 51 ± 16 ans, hommes: 59 %), 21,3 % presentaient une maladie renale chronique et 9,8 % une macroangiopathie (5 accidents vasculaires cerebraux (AVC), 9 coronaropathies, 1 gangrene et 9 gestes de revascularisation). En 2013, 14 nouvelles manifestations de macroangiopathie etaient apparues (3 AVC, 4 coronaropathies, 7 revascularisations). L'AF de 2009 etait superieure chez les sujets ayant une MA prealable (2,57 ± 0,70 vs autres 2,08 ± 0,54, p =0,014). Ce resultat restait significatif apres ajustement a l'âge, au sexe, au tabac, a la duree du diabete, a la presence d'une hypertension arterielle et d'une maladie renale chronique (Exp (B)=2,94 ; p =0,023). Les sujets ayant une nouvelle macroangiopathie en 2013, avaient une AF initiale superieure (2,58 ± 0,72 vs autres 2,10 ± 0,55, p =0,002). Ce resultat restait significatif apres les memes ajustements (Exp (B)=3,3 ; p =0,032) mais devenait non significatif une fois ajuste a la presence d'une macroangiopathie prealable. Conclusion Au cours du DT1, l'AF est associee a la survenue d'evenements cardiovasculaires independamment des facteurs de risque classiques. Cette association persiste apres ajustement a la maladie renale chronique. Le facteur predictif le plus puissant demeure cependant l'existence d'une macroangiopathie prealable. Declaration d’interet Les auteurs declarent ne pas avoir d'interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

Introduction et but de l’etude La mesure non-invasive de l’autofluorescence (AF) cutanee, quantifie l’accumulation des produits de glycation avances (AGEs). Les AGEs sont des molecules toxiques dont l’accumulation refleterait l’exposition a l’hyperglycemie chronique, ou a la deficience renale au long cours, temoignant de la « memoire metabolique ». Chez les personnes âgees, l’AF pourrait etre un indicateur de l’anciennete d’un diabete ou d’une insuffisance renale. L’objectif etait d’analyser l’association entre la mesure d’AF cutanee et le niveau glycemique / la fonction renale, mesures 10 ans auparavant des personnes âgees de la cohorte des 3-Cites (3C). Materiel et methodes Dans cette etude de cohorte retrospective, 328 personnes âgees de 75 ans et plus ont eu une mesure d’AF par AGE Reader © 10 ans apres leur inclusion dans 3C (T10). La mesure de la glycemie a jeun et de la creatininemie ainsi que le recueil des medicaments regulierement consommes avaient ete effectues a l’inclusion (T0) puis a T10. L’insuffisance renale a ete definie par un debit de filtration glomerulaire (DFG) Au cours du suivi, l’insuffisance renale et le diabete etaient consideres comme « absent» si les participants n’avaient pas la maladie a T0 ni a T10, « recent » si elle etait presente uniquement a T10 et « ancien » si elle etait presente a T0 et a T10. Les associations entre l’AF cutanee (variable dependante) et le statut renal et glycemique concomitant et 10 ans avant ont ete analysees par regressions lineaires multivariees ajustees sur l’âge, le sexe, l’hypertension, l’hypertriglyceridemie et le tabac. Resultats et Analyse statistique Par rapport a l’absence de diabete (N = 282), seul un diabete ancien (N = 19) etait significative-ment associe a une AF plus elevee de 0,38 UA (IC95 % 0,08 ; 0,69), les diabetiques recents (N = 27) avaient une AF intermediaire (β = 0,12, IC95 % −0,14 ; 0,39), apres ajustement. De la meme maniere, par rapport a l’absence d’une d’insuffisance renale (N = 191), seule une insuffisance renale ancienne (N = 34) etait significativement associee a une AF plus elevee 0,29 UA (IC95 % 0,05 ; 0,52), les insuffisants renaux recents avaient une AF intermediaire (β = 0,15, IC95 % −0,14 ; 0,39), apres ajustement. L’AF etait significativement associee a une elevation 10 ans auparavant de la glycemie de 1 mmol/L (P = 0,08, IC95 % 0,01 ; 0,15), mais pas l’elevation de la glycemie concomitante. Par contre l’AF etait significativement associee a une elevation 10 ans auparavant mais aussi concomitante du DFG de 10 mL/min/1,73 m2 (P = −0,07, IC95 % −0,12 ; 0,00 et β = −0,08, IC95 % −0,13 ; 0,00, respectivement). Conclusion L’AF cutanee reflete le statut glycemique et renal des personnes âgees 10 ans auparavant. Compte tenu du caractere l’insidieux du diabete et de l’insuffisance renale, cette methode non-invasive, pourrait aider a identifier les personnes a plus haut risques de complication.

Objective Advanced glycation end products (AGEs) are involved in diabetes complications. We aimed to investigate whether the accumulation of AGEs measured by skin autofluorescence (sAF) was associated with signs of diabetic peripheral neuropathy and to sensitivity, pain, motor and autonomic function 4 years later in patients with type 1 diabetes. Methods At baseline, 188 patients (age 51 years, diabetes duration 22 years) underwent skin autofluorescence measurement using the AGE Reader. Four years later, signs of diabetic peripheral neuropathy were defined as the presence of neuropathic pain and/or feet sensory loss or foot ulceration. Neurological tests were systematically performed: vibration perception threshold by neuroesthesiometry, neuropathic pain by the Douleur Neuropathique en 4 Questions score, muscle strength by dynamometry and electrochemical skin conductance. Multivariate analyses were adjusted by age, sex, height, body mass index, tobacco, HbA1c , diabetes duration, estimated glomerular filtration rate and albumin excretion rate. Results At the 4-year follow-up, 13.8% of patients had signs of diabetic peripheral neuropathy. The baseline sAF was higher in those with signs of diabetic peripheral neuropathy (2.5 ± 0.7 vs 2.1 ± 0.5 arbitrary units (AU), p 2.4 AU) compared with the lowest quartiles after multivariate adjustment. Conclusion This non-invasive measurement of skin autofluorescence may have a value for diabetic peripheral neuropathy in type 1 diabetes and a potential clinical utility for detection of diabetic peripheral neuropathy. Copyright © 2016 John Wiley & Sons, Ltd.

Introduction Certaines recommandations internationales exigent la mesure de la vitesse de conduction nerveuse(VCN) pour etablir le diagnostic de neuropathie diabetique. Nous la mesurons par DPN-Check, au lit du patient. La VCN est elle influencee par sa glycemie ? Patients et Methodes 23 sujets diabetiques hospitalises ont eu des mesures repetees par DPN Check, en hyperglycemie (a l'admission) puis en normoglycemie (trois jours apres). 10 sujets controles ont aussi eu des mesures repetees afin de verifier la reproductibilite. Tous beneficiaient de 4 mesures par DPN Check, applique au nerf sural : VCN et amplitude de potentiel(PA), bilaterales. Nous avons compare nos mesures, aux deux niveaux glycemiques, par tests t pour echantillons apparies et entre les groupes par ANOVA. Resultats Chez les 10 sujets normaux(20 % d'hommes, âge 22,6 ± 1,2 an, glycemies digitales a 0,91 ± 0,17 g/L), la reproductibilite etait excellente pour les VCN (ICC a 0,84 (0,40-0,96) a droite et 0,99 (0,97-1,00) a gauche) et bonne pour les PA (ICC a 0,63 (0,09-0,89) a droite et 0,75 (0,26-0,93) a gauche). Les 23 patients diabetiques(47,8 % hommes) etaient âges de 56,7 ± 15,0 ans, duree de diabete 18 ± 16 ans et HbA 1c 8,9 ± 2,7 %. Leurs mesures etaient realisees en hyperglycemie (2,47 ± 0,41 g/L) puis en normoglycemie(1,17 ± 0,24 g/L ; p p = 0,012), les PA de 6,6 ± 5,6 a 7,7 ± 6,0 V ( p = 0,065). En hyper comme en normoglycemie, ces valeurs etaient significativement alterees par rapport a celles des controles non diabetiques (VC N = 58 ± 4 ; PA : 14,7 ± 4,0 ; p 15V aux hallux), leurs VCN etaient significativement alterees en hyperglycemie a 37 ± 6 m/s par rapport aux 12 qui avaient une sensi-bilite vibratoire normale (47 ± 8 ; p = 0,04) et s'amelioraient en normoglycemie a 44 ± 6 (50 ± 7 si sensibilite normale ; p = 0,03). Conclusions Le DPN-Check fournit des mesures reproductibles de VCN et PA, realisables en 10 minutes au lit du patient. Les resultats sont alteres en cas de neuropathie. Les mesures de VCN sont influencees par le niveau glycemique et s'ameliorent de 6 m/s en normoglycemie.

Introduction Au cours du diabete de type 1 (DT1) la maladie renale chronique (MRC) est definie par l'alteration du debit de filtration glomerulaire (DFG 2 ) et/ou de l'excretion urinaire d'albumine (EUA ≥ 30 mg/24 h L'accumulation des produits avances de la glycation, mesurable par autofluorescence cuta-nee (AFC), joue probablement un role dans cette atteinte renale. Objectif : Evaluer la relation entre l'AFC et le risque d'atteinte renale 4 ans plus tard chez le DT1. Patients et Methodes Nous avons collige les caracteristiques cliniques et biologiques de sujets DT1 en 2009 et 2013. L'AFC a ete mesuree a l'inclusion avec l'AGE ReaderTM (DiagnOpticsTechnologies B.V., Groningen, Netherlands). Le profil renal des patients (DFG estime par la formule EPI-CKD, EUA, MRC) a ete analyse a l'inclusion puis apres 4 ans. Analyse statistique avec le logiciel SPSS (Anova, regressions lineaires et logistiques). Resultats 243 sujets ont ete inclus (59 % hommes, âge moyen : 51 ± 16 ans, duree du diabete : 23 ± 27 ans, IMC : 25 ± 8 kg/m 2 , HbA 1c : 7,6 ± 2,3 %). Profil renal a l'inclusion : 15,0 % des sujets avaient une EUA ≥ 30 mg/24 h, 13,9 % avaient un DFG 2 , 21,3 % presentaient une MRC. Apres 4 ans, l'incidence des nouvelles alterations renales etait respectivement de 5,3 %, 2,9 % et 6,1 %. Une correlation inverse etait retrouvee entre AFC et DFG quatre ans plus tard (r = − 0,38, p = 0,0001). Les sujets ayant un DFG 2 a 4 ans avaient une AFC initiale plus elevee que ceux dont le DFG etait normal : 2,45 ± 0,68 vs 2,06 ± 0,50, p = 0,04. Ce resultat restait significatif apres ajustement a l'âge, au sexe, au tabac, a la duree du diabete, a la presence d'une hypertension arterielle, a l'antecedent de macroangiopathie, a l'EUA ≥ 30 mg/24 h et au DFG 2 a l'inclusion (Exp (B) = 4,31 [1,31-14,19] ; p = 0,016). L'AFC n'etait pas significativement differente chez les sujets ayant une microalbuminurie pathologique ou une MRC incidentes a 4 ans compares aux sujets qui en etaient indemnes. Conclusions Chez le DT1, l'AFC predit la survenue d'une alteration du debit de filtration glomerulaire independamment de la microalbuminurie et de la fonction renale initiales.

Introduction La mesure non-invasive de l'autofluorescence (AF) cutanee des produits de glycation avances (AGE), est un reflet de la « memoire metabolique ». Notre objectif a ete d'identifier les facteurs associes a l'evolution de l'AF sur 4 ans, puis d'analyser la relation entre cette evolution et l'atteinte renale a 4 ans de suivi, chez des patients atteint d'un diabete de type 1 (DT1). Patients et Methodes Dans cette etude prospective, 154 patients ayant un DT1 ont eu deux mesures d'AF (AGE READER, Diagnoptics) : a l'inclusion en 2009, puis a 4 ans de suivi (2013). Les evenements etudies a 4 ans de suivi etaient la presence d'une diminution du debit de filtration glomerulaire (DFG, par la formule EPI-CKD 2 ) ou d'une micro ou macro-albuminurie (Albuminurie > 30mg/24h). Les associations ont ete analysees grâce a un modele de regression logistique multivarie. Resultats A l'inclusion les 154 sujets DT1 etaient âges de 51±15 ans, leur duree du diabete 23±13 ans, leur HbA 1c 7,6±0,9 %, 32 (20,7 %) etaient traites par pompe externe a insuline. En 4 ans de suivi l'AF a significativement augmente de 2,13±0,56 a 2,48±0,68UA, ( p 2 (OR=1,20 IC 95 %=1,02-1,43 p =0,03) et de micro ou macro-albuminurie (OR=1,32 IC 95 %=1,01-1,73 p =0,04) a 4 ans de suivi, apres multi-ajustement. Chez 22 sujets (15 %), l'AF a diminue pendant le suivi. Les facteurs a l'inclusion associes a cette diminution de l'AF etaient l'utilisation de la pompe a insuline (OR=3,01 IC 95 %=1,02-8,89, p =0,03) et un DFG augmente (OR=1,03 IC 95 %=1,00-1,07 p =0,04) apres ajustement sur l'âge, la duree du diabete et l'HbA 1c . Conclusions L'utilisation de la pompe parait avoir un effet sur l'evolution de L'AF cutanee des AGE, marqueur du risque de complications renales dans le DT1.

Introduction Certaines recommandations internationales exigent la mesure de la vitesse de conduction nerveuse (VCN) pour etablir le diagnostic de neuropathie diabetique. Nous la mesurons par DPN-Check, au lit du patient. La VCN estelle influencee par sa glycemie ? Patients et Methodes 23 sujets diabetiques hospitalises ont eu des mesures repetees par DPN Check, en hyperglycemie (a l'admission) puis en normoglycemie (trois jours apres). 10 sujets controles ont aussi eu des mesures repetees afin de verifier la reproductibilite. Tous beneficiaient au total de 4 mesures par le par DPN Check, applique au nerf sural : VCN et amplitude de potentiel (PA), de maniere bilaterale. Resultats Chez les 10 sujets normaux (20 % d'hommes, âge 22,6 ± 1,2 an, glycemies digitales a 0,91 ± 0,17 g/L), la reproductibilite etait excellente pour les VCN (ICC a 0,84 (0,40-0,96) a droite et 0,99 (0,97-1,00) a gauche) et bonne pour les PA (ICC a 0,63 (0,09-0,89) a droite et 0,75 (0,26-0,93) a gauche). Les 23 patients diabetiques (47,8 % hommes), etaient âges de 56,7 ± 15,0 ans, duree de diabete 18 ± 16 ans et HbA1c 8,9 ± 2,7 %. Leurs mesures ont ete realisees en hyperglycemie (2,47 ± 0,41 g/L) puis en normoglycemie (1,17 ± 0,24 g/L ; p 15V aux hallux), leurs VCN etaient significativement alterees en hyperglycemie a 37 ± 6 m/s par rapport aux 12 qui avaient une sensibilite vibratoire normale (47 ± 8 ; p = 0,04) et s'amelioraient en normoglycemie a 44 ± 6 (50 ± 7 si sensibilite normale ; p = 0,03). Conclusions Le DPN-Check fournit des mesures reproductibles de VCN et de PA, realisables en 10 minutes au lit du patient. Les resultats sont alteres en cas de neuropathie. Les mesures de VCN sont influencees par le niveau glycemique et s'ameliorent de 6 m/s en normoglycemie.

Introduction Le diabete et l’insuffisance renale chronique peuvent engendrer au long cours des complications degeneratives. La mesure non invasive par auto-fluorescence (AF) cutanee du depot tissulaire des produits de glycation avances (AGEs), impliques dans ce phenomene, pourrait etre un biomarqueur de troubles glycemiques et renaux anciens chez les personnes âgees. L’objectif etait d’analyser l’association entre l’AF cutanee et l’HbA1c et le debit de filtration glomerulaire (DFG) mesures 10 ans auparavant chez les personnes âgees de la cohorte des 3-Cites (3C). Materiels et methodes Dans cette cohorte retrospective, 125 participants âges de 78 ans et plus ont eu une mesure d’AF cutanee par AGE Reader© a 10 ans de suivi (T10). L’HbA1c et le DFG (equation MDRD) ont ete mesures a l’inclusion (T0) et a T10. Les associations entre l’AF cutanee (variable dependante) et l’HbA1c et le DFG concomitants, et 10 ans auparavant, ont ete analysees par regression lineaire multivariee ajustee sur l’âge, le sexe, l’hypertension, l’IMC, l’hypertriglyceridemie et le tabac. Resultats A 10 ans de suivi l’AF moyenne etait de 2,89 ± 0,71 UA. En 10 ans la prevalence du diabete est passee de 15,2 % a 26,4 %, l’HbA1c a augmente de 5,9 a 6,3 % et le DFG a diminue de 10 ml/min/1,73 m2. Une HbA1c plus haute de 1 % et un DFG plus faible de 10 ml/min/1,73 m2, 10 ans auparavant etaient respectivement associes a une augmentation de 0,15 unite arbitraire (UA) (IC 95 %: 0,02 ; 0,28) et de 0,10 UA (IC 95 %: 0,01 ; 0,16) de l’AF, apres ajuste-ment. Par contre le taux d’HbA1c et le DFG concomitants n’etaient pas associes a l’AF. Conclusion L’AF cutanee reflete le statut glycemique et renal des personnes âgees 10 ans auparavant, ce qui parait bien correspondre a un biomarqueur de memoire metabolique. Declaration d’interet Les auteurs declarent ne pas avoir d’interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

Introduction Le diabete gestationnel, defini comme un trouble de la regulation glucidique apparaissant ou decouvert au cours de la grossesse, inclut des patientes ayant un diabete meconnu preexistant a la grossesse. L’autofluorescence (AF) cutanee reflete l’accumulation cutanee des produits de glycation avancee. L’objectif de notre etude est de determiner si l’AF cutanee pourrait detecter des patientes ayant eu des hyperglycemies anterieures. Patients et methodes Nous avons mesure l’AF cutanee grâce a l’AGE ReaderTM, entre la 24 e et la 30 e semaines d’amenorrhee chez des patientes enceintes adressees pour la prise en charge du diabete. Resultats Nous avons inclus 230 patientes (200 avec diabete gestationnel et 30 avec diabete preexistant : 21 type 1 et 9 type 2). L’AF cutanee etait significativement plus elevee chez les patientes avec diabete preexistant (1,97 ± 0,43 A.U.) que chez les patientes avec un diabete gestationnel (1,77 ± 0,32) ; ( p = 0,0007 ajuste sur l’âge). Parmi les patientes ayant un diabete gestationnel, 71 avaient une histoire anterieure d’hyperglycemie (antecedent de diabete gestationnel : n = 49, et/ou de macrosomie lors d’une grossesse precedente : n = 25, et/ou hyperglycemie precoce avant la 24 e semaine d’amenorrhee lors de la grossesse actuelle, n = 29). L’HbA1C et la fructosaminemie de ces patientes ne differaient pas de celles des autres, mais elles avaient une AF cutanee plus elevee (1,83 ± 0,35) que les patientes sans antecedent d’hyperglycemie (1,73 ± 0,30), ( p = 0,04, NS ajuste sur l’âge). L’AF cutanee augmentait significativement avec le nombre de criteres d’hyperglycemie anterieure ( p de tendance = 0,008), et sa valeur restait significativement superieure apres ajustement a l’âge, chez les patientes qui presentaient deux ou trois criteres d’hyperglycemie anterieure. Conclusion Ces resultats suggerent que l’AF cutanee est un marqueur de la memoire metabolique chez des patientes enceintes diabetiques. Notre projet est maintenant d’etudier si l’autofluorescence peut aider a predire le pronostic de l’enfant (macrosomie ?), et de la mere (diabete persistant apres grossesse ?). Declaration d’interet Les auteurs declarent ne pas avoir d’interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.