Occurrence and predictors of retinopathy and visual acuity in type 2 diabetic patients and control subjects 10-year follow-up from the diagnosis

Rozwój retinopatii i zaburzeń ostrości widzenia oraz czynniki ryzyka ich wystąpienia u pacjentów z nowo rozpoznaną cukrzycą i w grupie kontrolnej u osób bez cukrzycy. Prospektywne, 10-letnie badanie objęło reprezentatywną grupę 133 chorych (70 mężczyzn i 63 kobiety) na cukrzycę typu 2, świeżo rozpoznaną w latach 1979-1981, oraz 144 osoby (62 mężczyzn i 82 kobiety) z grupy kontrolnej bez cukrzycy, wyłonione z populacji ogólnej. Częstość retinopatii oraz stopień jej zaawansowania oceniano na podstawie 45o zdjęć dna oka wykonywanych na początku badania oraz po 5 i 10 latach. Po 10 latach obserwacji u chorych na cukrzycę stwierdzono gorszą ostrość wzroku niż u osób z grupy kontrolnej. Upośledzenie ostrości widzenia wykazywało odwrotną korelację z wartościami HbA1c oznaczonymi po 5 latach. Częstość retinopatii u chorych na cukrzycę typu 2 wzrastała gwałtownie po 5 latach, a po 10 latach obserwacji już u 55% stwierdzano cechy retinopatii. Natomiast u osób z grupy kontrolnej częstość retinopatii była niewielka, lecz wykrywalna. Zła kontrola glikemii była u chorych na cukrzycę najistotniejszym czynnikiem pozwalającym przewidywać rozwój retinopatii. Wartości ciśnienia tętniczego były wyższe, a mikroalbuminuria częstsza u osób z grupy kontrolnej, u których stwierdzano retinopatię. U chorych ze świeżo rozpoznaną cukrzycą typu 2 ostrość widzenia ulegała pogorszeniu, a częstość retinopatii rosła wraz z czasem trwania choroby oraz złą kontrolą glikemii. Wyższe ciśnienie tętnicze oraz mikroalbuminuria pozwalały przewidywać rozwój retinopatii u osób z grupy kontrolnej.The evolution of visual acuity and retinopathy and their risk factors in patients with newly diagnosed type 2 diabetes and in control subjects. A 10-year prospective study consisting of a representative group of 133 (70 men, 63 women) newly diagnosed type 2 diabetic patients diagnosed at health centers between 1979 and 1981 and 144 (62 men, 82 women) non-diabetic control subjects recruited from the population register. The frequency of retinopathy was determined by grading of 45° fundus photographs at baseline and after 5 and 10 years. By the 10-year follow-up the diabetic patients had lower visual acuity than the control subjects. The im-pairment of the visual acuity correlated inversely to HbA1c value of the 5-year examination. The frequency of retinopathy in type 2 diabetic patients increased sharply after 5 years and at 10-year 55% of diabetic patients had signs of retinopathy. The frequency of retinopathy in the control subjects was low, but detectable. In the diabetic patients poor glycemic control was the most important predictive factor for the development of retinopathy. In the control subjects blood pressure levels were higher and microalbuminuria more common in those with than in those without retinopathy. The visual acuity deteriorated and the frequency of retinopathy increased in newly diagnosed type 2 diabetic patients with duration of disease and poor glycemic control. Interestingly, higher blood pressure levels and microalbuminuria predicted retinopathy in control subjects

Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.

Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights

Physical activity attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children

Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (pinteraction= 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Concl

Population-level effects of the national diabetes prevention programme (FIN-D2D) on the body weight, the waist circumference, and the prevalence of obesity

BACKGROUND: The implementation project of the national diabetes prevention programme in Finland, FIN-D2D, was carried out in primary health care in the area of five hospital districts during 2003-2007. METHODS: The population strategy of FIN-D2D was primarily aimed at increasing the awareness of type 2 diabetes and preventing obesity. To investigate the effects of this strategy, we studied the changes in the prevalence of obesity, overweight, and central obesity among a random independent sample of individuals aged 45-74 years in the FIN-D2D area; and assessed whether they differed from a sample of individuals in the control area, which consisted of four geographical areas not participating in FIN-D2D (FINRISK study). Data was obtained for 5850/ 6406 (in the beginning/ in the end) individuals. The duration of the observation period varied from three to five years. RESULTS: The mean body weight decreased from 78.7 to 78.1 kg (p = 0.041) in the FIN-D2D area, and from 78.7 to 78.0 kg (p = NS) in the control area. The prevalence of obesity (BMI ≥30 kg/m(2)) decreased in the FIN-D2D area (26.5% vs. 24.4%, p = 0.015), and in the control area (28.4% vs. 25.2%, p = 0.005). The prevalence of morbid obesity (BMI ≥40 kg/m(2)) remained unchanged in the FIN-D2D area, but increased in the control area (1.2% vs. 2.3%, p = 0.007). The mean waist circumference remained unchanged in the FIN-D2D area, but increased in the control area (92.8 vs. 94.0 cm, p = 0.005). CONCLUSIONS: The prevalence of obesity may be decreasing among 45-74 year old Finns. We still need a longer time perspective and future studies to see whether this favourable trend can be sustained in Finland. The actions of this implementation project can at least partly explain the differences in the mean waist circumference and the prevalence of morbid obesity between the intervention and control areas.Peer reviewe

FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m2, P = 1.9 × 10−105), and all participants (0.30 [0.30, 0.35] kg/m2, P = 3.6 × 10−107). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10−16), and relative weak associations with lower total energy intake (−6.4 [−10.1, −2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (−0.07 [−0.11, −0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10−9) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposit

Ten-Year Mortality and Cardiovascular Morbidity in the Finnish Diabetes Prevention Study—Secondary Analysis of the Randomized Trial

The Finnish Diabetes Prevention Study (DPS) was a randomized controlled trial, which showed that it is possible to prevent type 2 diabetes by lifestyle changes. The aim of the present study was to examine whether the lifestyle intervention had an effect on the ten-year mortality and cardiovascular morbidity in the DPS participants originally randomized either into an intervention or control group. Furthermore, we compared these results with a population-based cohort comprising individuals of varying glucose tolerance states.Middle-aged, overweight people with IGT (n = 522) were randomized into intensive intervention (including physical activity, weight reduction and dietary counseling), or control "mini-intervention" group. Median length of the intervention period was 4 years and the mean follow-up was 10.6 years. The population-based reference study cohort included 1881 individuals (1570 with normal glucose tolerance, 183 with IGT, 59 with screen-detected type 2 diabetes, 69 with previously known type 2 diabetes) with the mean follow-up of 13.8 years. Mortality and cardiovascular morbidity data were collected from the national Hospital Discharge Register and Causes of Death Register. Among the DPS participants who consented for register linkage (n = 505), total mortality (2.2 vs. 3.8 per 1000 person years, hazard ratio HR = 0.57, 95% CI 0.21-1.58) and cardiovascular morbidity (22.9 vs. 22.0 per 1000 person years, HR = 1.04, 95% CI 0.72-1.51) did not differ significantly between the intervention and control groups. Compared with the population-based cohort with impaired glucose tolerance, adjusted HRs were 0.21 (95% CI 0.09-0.52) and 0.39 (95% CI 0.20-0.79) for total mortality, and 0.89 (95% CI 0.62-1.27) and 0.87 (0.60-1.27) for cardiovascular morbidity in the intervention and control groups of the DPS, respectively. The risk of death in DPS combined cohort was markedly lower than in FINRISK IGT cohort (adjusted HR 0.30, 95% CI 0.17-0.54), but there was no significant difference in the risk of CVD (adjusted HR 0.88, 95% CI 0.64-1.21).Lifestyle intervention among persons with IGT did not decrease cardiovascular morbidity during the first 10 years of follow-up. However, the statistical power may not be sufficient to detect small differences between the intervention and control groups. Low total mortality among participants of the DPS compared with individuals with IGT in the general population could be ascribed to a lower cardiovascular risk profile at baseline and regular follow-up.ClinicalTrials.gov NCT00518167

PUFA omega-3 and omega-6 biomarkers and sleep : a pooled analysis of cohort studies on behalf of the Fatty Acids and Outcomes Research Consortium (FORCE)

Background: n-3 and n-6 PUFAs have physiologic roles in sleep processes. but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters. Objectives: We sought to assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Research Consortium. Methods: Harmonized, de novo. individual-level analyses were performed and pooled across 12 cohorts. Participants were 35-96 y old and from 5 nations. Circulating measures included alpha-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA), DHA, EPA + DPA DHA, linoleic acid, and arachidonic acid. Sleep duration (10 cohorts. n = 18.791) was categorized as short (= 9 h). Difficulty falling asleep (8 cohorts, n = 12,500) was categorized as yes or no. Associations between PUFAs, sleep duration, and difficulty falling sleeping were assessed by cross-sectional multinomial logistic regression using standardized protocols and covariates. Cohort-specific multivariable-adjusted ORs per quintile of PUFAs were pooled with inverse-variance weighted meta-analysis. Results: In pooled analysis adjusted for sociodemographic characteristics and health status, participants with higher very long-chain n-3 PUFAs were less likely to have long sleep duration. In the top compared with the bottom quintiles. the multivariable-adjusted ORs (95% CIs) for long sleep were 0.78 (95% CI: 0.65, 0.95) for DHA and 0.76 (95% CI: 0.63, 0.93) for EPA + DPA + DHA. Significant associations for ALA and n-6 PUFA with short sleep duration or difficulty falling sleeping were not identified. Conclusions: Participants with higher concentrations of very long-chain n-3 PUFAs were less likely to have long sleep duration. While objective biomarkers reduce recall bias and misclassification, the cross-sectional design limits assessment of the temporal nature of this relation. These novel findings across 12 cohorts highlight the need for experimental and biological assessments of very long-chain n-3 PUFAs and sleep duration.Peer reviewe