Kalina Rajaobelina

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.

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 in acute kidney injury

We were interested by the article from De Corte et al. about the poor long-term outcome after acute kidney injury (AKI) [1]. Besides initial oliguria, the three predictors for dialysis dependence were age, diabetes, and chronic kidney disease (CKD), which have previously been related to the accumulation of advanced glycation end-products (AGEs) as evaluated by skin autofluorescence (sAF). sAF is an indirect marker that has been related to the skin concentrations of fluorescent (pentosidine) and non-fluorescent AGEs (carboxy-methyl-lysine and carboxy-ethyl-lysine) in skin biopsies of hemodialized subjects [2]. Could sAF be altered in AKI? From July 2014 to April 2015, we measured sAF with an AGE-Reader (DiagnOpticsTechnologies B.V., Groningen, Netherlands) in 35 patients admitted for AKI, staged F (RIFLE). Their results were compared to their theoretical values ((0.024 × Years of age) + 0.83 [3]) and to those of 35 patients with CKD waiting for a renal graft. All the patients gave written informed consent and the study was approved by the Comité de Protection des Personnes Sud-Ouest et Outre-Mer 3 (Bordeaux). A multivariate linear regression analysis was performed to study the relationship between sAF and the duration of renal failure and to adjust it to the age and gender of the subjects. The patients with AKI and CKD had similar age, gender, body-mass index, and creatinine levels (Table 1). The sAF was lower in AKI than CKD, still significant (p < 0.001) after adjustment for age, gender, and creatinine. The sAF were higher than the theoretical values calculated from age: 2.31 ± 0.36 arbitrary units (AU; p < 0.001 for both AKI and CKD). The sAF was related to the duration of renal failure and was still significant (B = +0.43, p = 0.02) after adjustment for age and gender (Fig. 1). In six patients with AKI, a second sAF measurement was performed10 ± 3 days later: the sAF increased from 2.61 ± 0.72 to 3.03 ± 0.74 (p < 0.05). Our results show that sAF is lower in AKI than in CKD and relates to the duration of renal failure, as expected. sAF is considered as a marker of metabolic memory [4], reflecting the accumulation of AGEs in the skin [2]. In our patients who could be analyzed twice, sAF increased by +0.4 AU after only 10 days, so they probably had normal sAF when their AKI started one month before. A normal, early measured sAF may therefore help to distinguish acute from chronic renal failure. The sAF was already high, and increased rapidly, in our patients with AKI. This concurs well with the quick rising plasmatic concentrations of AGEs in experimentally induced acute renal failure in rats [5]. High sAF has also been reported in patients admitted to intensive care units

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.

Comment on Kelly et al. Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes. Diabetes Care 2018;41:120–127

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 …

A parental history of diabetes is associated with a high risk of retinopathy in patients with type 2 diabetes

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