Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.

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.

Strong adherence to dietary and lifestyle recommendations is associated with decreased type 2 diabetes risk in the AusDiab cohort study.

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.

Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.

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.

Diet and risk of diabetic retinopathy: a systematic review.

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.

Progression of skin autofluorescence of AGEs over 4 years in patients with type 1 diabetes.

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 (ß = -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 (<90 mL/min/1.73 m2 ): OR 1.22, P = .03 at 4 years of follow-up. CONCLUSIONS: The skin autofluorescence of advanced glycation end-products progresses in patients with type 1 diabetes, more if they have diabetic nephropathy, less if they are treated by continuous subcutaneous insulin infusion. This progression is associated with the development of nephropathy.

Skin autofluorescence predicts cardio-renal outcome in type 1 diabetes: a longitudinal study.

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 <60 ml/min/1.73 m(2) had a SAF higher than patients with normal eGFR. After adjustment for the previous criteria, SAF remained associated with the risk of impaired incident eGFR (OR 7.42 [95 % CI 1.59-34.65], p = 0.018). No relation was found between SAF and increased AER 4 years later. CONCLUSIONS: SAF predicts MVE in patients with T1D, adjusted for cardiovascular risk factors but the most powerful predictive factor remains history of MVE. SAF also predicts eGFR impairment, adjusted for initial AER and renal function. SAF could be a useful non-invasive tool for estimating risk of cardiovascular or renal impairment in patients with T1D.

Population attributable fractions of the main type 2 diabetes mellitus risk factors in women: Findings from the French E3N cohort.

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 Générale 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.

High iodine dietary intake is associated with type 2 diabetes among women of the E3N-EPIC cohort study.

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.

Skin Autofluorescence of Pregnant Women With Diabetes Predicts the Macrosomia of Their Children.

Advanced glycation end products (AGEs) accumulated during long-term hyperglycemia are involved in diabetes complications and can be estimated by skin autofluorescence (sAF). During pregnancy, hyperglycemia exposes women to the risk of having a macrosomic newborn. The aim of this study was to determine whether sAF of women with diabetes during a singleton pregnancy could predict macrosomia in their newborns. Using an AGE Reader, we measured the sAF at the first visit of 343 women who were referred to our diabetology department during years 2011-2015. Thirty-nine women had pregestational diabetes, 95 early gestational diabetes mellitus (GDM), and 209 late GDM. Macrosomia was defined as birth weight ≥4,000 g and/or large for gestational age ≥90th percentile. Forty-six newborns were macrosomic. Their mothers had 11% higher sAF compared with other mothers: 2.03 ± 0.30 arbitrary units (AUs) vs. 1.80 ± 0.34 (P < 0.0001). Using multivariate logistic regression, the relation between sAF and macrosomia was significant (odds ratio 4.13 for 1-AU increase of sAF [95% CI 1.46-11.71]) after adjusting for several potential confounders. This relation remained significant after further adjustment for HbA1c (among 263 women with available HbA1c) and for women with GDM only. sAF of pregnant women with diabetes, a marker of long-term hyperglycemic exposure, predicts macrosomia in their newborns.

Associations of circulating very-long-chain saturated fatty acids and incident type 2 diabetes: a pooled analysis of prospective cohort studies.

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.

Micronutrient dietary patterns associated with type 2 diabetes mellitus among women of the E3N-EPIC (Etude Epidémiologique auprès de femmes de l'Education Nationale) cohort study.

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 Epidémiologique auprès 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.

Nonlinear associations between dietary exposures to perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) and type 2 diabetes risk in women: Findings from the E3N cohort study.

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) ≤25 kg/m2). No association was found between dietary exposure to PFOS and T2D, except when considering only women with BMI≤25 kg/m2, in which a positive nonlinear association was observed (HR [95%CI] = 1.46 [1.09-1.96], 1.52 [1.09-2.11], and 1.44 [1.01-2.06] for the 6th, 8th, and 9th decile groups respectively). This is the first study to evaluate the association between dietary exposure to PFOA and PFOS and the risk of developing T2D in a large observational study with over 15 years of follow-up. The present study highlights the importance of studying the effects of EDCs in large epidemiological studies including not occupationally exposed populations, as well as the importance of considering exposure to PFOS and PFOA as a relevant risk factor for T2D.

Accumulation of advanced glycation end products evaluated by skin autofluorescence and incident frailty in older adults from the Bordeaux Three-City cohort.

AIM: We analyzed the cross-sectional and prospective relationships between the accumulation of advanced glycation end products (AGE), assessed by skin autofluorescence (AF) and frailty and its components. METHODS: A total of 423 participants of the Bordeaux sample of the Three-City study 75 years of age or older in 2009-2010 were included in the cross-sectional analysis. Among them, 255 initially non-frail participants were re-examined 4 years later. Skin AF (arbitrary units (AU)) was measured using the AGE Reader. Frailty was defined using Fried's criteria. Associations were assessed with logistic regression models. RESULTS: Mean skin AF at baseline was 2.81 ±0.68 AU and 16.8% participants were frail. Adjusted for sociodemographic and health characteristics, skin AF was associated neither with prevalent frailty as a whole (Odds Ratio (OR) = 1.2; 95% Confidence Interval: 0.8-1.9) nor with any of its components. Among 255 non-frail participants, 32 became frail over 4 years. In multivariate analyses, skin AF was not associated with incident frailty as a whole (OR = 1.0; 0.5-2.0) but with a doubled risk of incident exhaustion (OR = 2.0; 1.2-3.6) and low energy expenditure (OR = 2.0; 1.1-3.7). No association was observed with other criteria. CONCLUSION: In French older community-dwellers aged 75 years and over, the accumulation of AGEs evaluated by skin AF was not associated with prevalent or incident frailty but with the 4-year risk of exhaustion and low energy expenditure. Further studies with larger samples are needed to confirm our results.

Skin autofluorescence, renal insufficiency and retinopathy in patients with type 2 diabetes.

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 62years (standard deviation (SD) 10years), 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>60mL/min/1.73m2), 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.

Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies.

BACKGROUND: The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. METHODS: We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. FINDINGS: Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m2, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60-0·72, p<0·0001; I2=53·9%, pheterogeneity=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88-1·05; p=0·38; I2=63·0%, pheterogeneity<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all pheterogeneity≥0·13). INTERPRETATION: Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful. FUNDING: Funders are shown in the appendix.

Autofluorescence of Skin Advanced Glycation End Products: Marker of Metabolic Memory in Elderly Population.

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.