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AIM: To evaluate the association with diabetic kidney disease of single nucleotide polymorphisms (SNPs) that may contribute to mitochondrial dysfunction. METHODS: The mitochondrial genome and 1039 nuclear genes that are integral to mitochondrial function were investigated using a case (n = 823 individuals with diabetic kidney disease) vs. control (n = 903 individuals with diabetes and no renal disease) approach. All people included in the analysis were of white European origin and were diagnosed with Type 1 diabetes before the age of 31 years. Replication was conducted in 5093 people with similar phenotypes to those of the discovery collection. Association analyses were performed using the plink genetic analysis toolset, with adjustment for relevant covariates. RESULTS: A total of 25 SNPs were evaluated in the mitochondrial genome, but none were significantly associated with diabetic kidney disease or end-stage renal disease. A total of 38 SNPs in nuclear genes influencing mitochondrial function were nominally associated with diabetic kidney disease and 16 SNPS were associated with end-stage renal disease, secondary to diabetic kidney disease, with meta-analyses confirming the same direction of effect. Three independent signals (seven SNPs) were common to the replication data for both phenotypes with Type 1 diabetes and persistent proteinuria or end-stage renal disease. CONCLUSIONS: Our results suggest that SNPs in nuclear genes that influence mitochondrial function are significantly associated with diabetic kidney disease in a white European population.

Aims Glucagon-like peptide-1 receptor agonist studies have revealed clinically significant reductions in systolic blood pressure ( SBP). The aim was to investigate the time course of the anti-hypertensive effect of liraglutide treatment and potential underlying mechanisms. Methods We used an open-label, single-centre trial; 31 participants with Type 2 diabetes and hypertension completed the study. All participants were treated with liraglutide escalated to a maximum dose of 1.8 mg/day for 7 weeks, followed by a 21-day washout period. The primary outcome was a change in 24-h SBP. Results Twenty-four-h SBP increased by 10 mmHg on day 3 ( P = 0.008) and 7 mmHg on day 7 ( P = 0.033, 0.6 mg/day). On day 29, (1.8 mg/day), 24-h SBP was 7 mmHg lower compared with baseline ( P = 0.11). Following the treatment period (day 49) and after washout (day 70), 24-h BP was equivalent to baseline. In addition, extracellular volume ( ECV) was reduced by 2.0 l [95% confidence interval ( CI) = 1.0-3.1 l, P < 0.001] and midregional-pro-atrial natriuretic peptide ( MR-pro ANP) was reduced by 20% (95% CI = 12-28%, P < 0.001). Also, urinary albumin excretion declined by 30% (95% CI = 12-44%, P = 0.003), GFR by 11 ml/min/1.73 m2 (95% CI = 7.2-14.4 ml/min/1.73 m2, P < 0.001) and fractional albumin excretion by 29% (95% CI = 3-48%, P = 0.032). Conclusions Liraglutide treatment was associated with an initial increase in 24-h SBP, followed by a 7 mmHg reduction after escalation to 1.8 mg/day. This effect subsided after 4 weeks of maximum dose. Reductions in ECV and MR-pro ANP may explain the anti-hypertensive potential. Liraglutide treatment was associated with reversible reductions in albuminuria and GFR, which has to be confirmed in randomized trials. [ABSTRACT FROM AUTHOR]