High-sensitivity c-reactive protein and gamma-glutamyl transferase levels are synergistically associated with metabolic syndrome in community-dwelling persons

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. Increased high-sensitivity C-reactive protein (hsCRP) levels are associated with MetS and its components. Changes in gamma-glutamyl transferase (GGT) levels in response to oxidative stress are also associated with MetS, and the levels could be modulated by hsCRP.</p> <p>Methods</p> <p>From a single community, we recruited 822 men (mean age, 61 ± 14 years) and 1,097 women (63 ± 12 years) during their annual health examination. We investigated whether increased hsCRP and GGT levels are synergistically associated with MetS and insulin resistance evaluated by Homeostasis of model assessment of insulin resistance (HOMA-IR).</p> <p>Results</p> <p>Of these subjects, 141 men (17.2%) and 170 women (15.5%) had MetS. Participants with MetS had a higher hsCRP and GGT level than those without MetS in both genders, and the HOMA-IR increased significantly in correlation with an increase in hsCRP and GGT. In men, the adjusted odds ratios (95% confidence interval) for MetS across tertiles of hsCRP and GGT were 1.00, 1.69 (1.01-2.80), and 2.13 (1.29-3.52), and 1.00, 3.26 (1.84-5.78) and 6.11 (3.30-11.3), respectively. In women, the respective corresponding values were 1.00, 1.54 (0.92-2.60), and 3.08 (1.88-5.06), and 1.00, 1.70 (1.04-2.79) and 2.67 (1.66-4.30). The interaction between increased hsCRP and GGT was a significant and independent determinant for MetS and insulin resistance in both genders.</p> <p>Conclusions</p> <p>These results suggested that higher CRP and GGT levels were synergistically associated with MetS and insulin resistance, independently of other confounding factor in the general population.</p

Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to examine how lipid profiles are associated with insulin resistance in Japanese community-dwelling adults.</p> <p>Methods</p> <p>This cross-sectional study included 614 men aged 58 ± 14 (mean ± standard deviation; range, 20-89) years and 779 women aged 60 ± 12 (range, 21-88) years. The study sample were 1,042 (74.8%) non-obese (BMI < 25.0 kg/m²) and 351 (25.2%) overweight (BMI ≥ 25 kg/m²) subjects. Insulin resistance was defined by homeostasis model assessment of insulin resistance (HOMA-IR) of at least 2.5. The areas under the curve (AUC) of the receiver operating characteristic curves (ROC) were used to compare the power of these serum markers.</p> <p>Results</p> <p>In non-obese subjects, the best marker of insulin resistance was low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio of 0.74 (95% confidence interval (CI), 0.66-0.80). The HDL-C, triglyceride (TG)/HDL-C ratio, and non-HDL-C also discriminated insulin resistance, as the values for AUC were 0.31 (95% CI, 0.24-0.38), 0.69 (95% CI, 0.62-0.75) and 0.69 (95% CI, 0.62-0.75), respectively. In overweight subjects, the AUC for TG and TG/HDL-C ratio were 0.64 (0.58-0.71) and 0.64 (0.57-0.70), respectively. The optimal cut-off point to identifying insulin resistance for these markers yielded the following values: TG/HDL-C ratio of ≥1.50 and LDL-C/HDL-C ratio of ≥2.14 in non-obese subjects, and ≥2.20, ≥2.25 in overweight subjects. In non-obese subjects, the positive likelihood ratio was greatest for LDL-C/HDL-C ratio.</p> <p>Conclusion</p> <p>In non-obese Japanese adults, LDL-C/HDL-C ratio may be the best reliable marker of insulin resistance.</p

PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2

Nedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90-180, was significantly greater with nedosiran vs placebo (least squares mean [SE], +3507 [788] vs -1664 [1190], respectively; difference, 5172; 95% CI 2929-7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (<0.60 mmol/24 hours; <1.3 × ULN) Uox excretion on ≥2 consecutive visits starting at day 90 (50% vs 0; P = 0.002); this effect was mirrored in the nedosiran-treated PH1 subgroup (64.7% vs 0; P < 0.001). The PH1 subgroup maintained a sustained Uox reduction while on nedosiran, whereas no consistent effect was seen in the PH2 subgroup. Nedosiran-treated participants with PH1 also showed a significant reduction in plasma oxalate versus placebo (P = 0.017). Nedosiran was generally safe and well tolerated. In the nedosiran arm, the incidence of injection-site reactions was 9% (all mild and self-limiting). In conclusion, participants with PH1 receiving nedosiran had clinically meaningful reductions in Uox, the mediator of kidney damage in PH