The Genetic Landscape of Renal Complications in Type 1 Diabetes

Diabetes is the leading cause of end stage renal disease. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2,843 subjects, we estimated that the heritability of diabetic kidney disease was 35% ( p=6x10-3 ). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index ( p=2.2×10-5) and the risk of type 2 diabetes (p=6.1x10-4 ) were associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation ( p=1.1×10-4 ). Pathway analysis implicated ascorbate and aldarate metabolism ( p=9×10-6), and pentose and glucuronate interconversions ( p=3×10-6) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.  

Psychological factors associated with self-management among adolescents with Type 1 diabetes: a review

This review aims to synthesise the literature examining the psychosocial variables related to self-management (insulin adherence, non-adherence and administration, blood sugar monitoring, dietary behaviour, exercise behaviour) in adolescents with type 1 diabetes.
A systematic search of three electronic databases was carried out and, after the application of eligibility criteria, 21 articles were assessed for quality prior to data extraction. Numerous psychological factors were found to be associated with self-management; however, correlations were typically small to moderate. The strongest associations were found between social anxiety and diet (among males); greater intrinsic motivation, conscientiousness and diet; and extraversion and exercise.

Serum Fatty Acid Binding Protein 4 (FABP4) Predicts Pre-eclampsia in Women with Type 1 Diabetes

Objective: To examine the association between fatty acid binding protein 4 (FABP4) and pre-eclampsia risk in women with type 1 diabetes.
Reesearch Design and Methods: Serum FABP4 was measured in 710 women from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT) in early pregnancy and in the second trimester (median 14 and 26 weeks gestation, respectively).
Results: FABP4 was significantly elevated in early pregnancy (geometric mean 15.8 ng/mL [interquartile range 11.6–21.4] vs. 12.7 ng/mL [interquartile range 9.6–17]; P < 0.001) and the second trimester (18.8 ng/mL [interquartile range 13.6–25.8] vs. 14.6 ng/mL [interquartile range 10.8–19.7]; P < 0.001) in women in whom pre-eclampsia later developed. Elevated second-trimester FABP4 level was independently associated with pre-eclampsia (odds ratio 2.87 [95% CI 1.24, 6.68], P = 0.03). The addition of FABP4 to established risk factors significantly improved net reclassification improvement at both time points and integrated discrimination improvement in the second trimester.
Conclusions: Increased second-trimester FABP4 independently predicted pre-eclampsia and significantly improved reclassification and discrimination. FABP4 shows potential as a novel biomarker for pre-eclampsia prediction in women with type 1 diabetes.