Supplementary Material for: Human Cardiovascular Disease IBC Chip-Wide Association with Weight Loss and Weight Regain in the Look AHEAD Trial

<b><i>Background/Aims:</i></b> The present study identified genetic predictors of weight change during behavioral weight loss treatment. <b><i>Methods:</i></b> Participants were 3,899 overweight/obese individuals with type 2 diabetes from Look AHEAD, a randomized controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education, on cardiovascular outcomes. Analyses focused on associations of single nucleotide polymorphisms (SNPs) on the Illumina CARe iSelect (IBC) chip (minor allele frequency >5%; n = 31,959) with weight change at year 1 and year 4, and weight regain at year 4, among individuals who lost ≥3% at year 1. <b><i>Results:</i></b> Two novel regions of significant chip-wide association with year-1 weight loss in ILI were identified (p < 2.96E-06). <i>ABCB11 </i>rs484066 was associated with 1.16 kg higher weight per minor allele at year 1, whereas <i>TNFRSF11A,</i> or<i> RANK,</i> rs17069904 was associated with 1.70 kg lower weight per allele at year 1. <b><i>Conclusions:</i></b> This study, the largest to date on genetic predictors of weight loss and regain, indicates that SNPs within <i>ABCB11</i>, related to bile salt transfer, and <i>TNFRSF11A</i>, implicated in adipose tissue physiology, predict the magnitude of weight loss during behavioral intervention. These results provide new insights into potential biological mechanisms and may ultimately inform weight loss treatment

Supplementary Material for: Association of Serum Amyloid A with Kidney Outcomes and All-Cause Mortality in American Indians with Type 2 Diabetes

<p><b><i>Background:</i></b> Serum amyloid A (SAA) induces inflammation and apoptosis in kidney cells and is found to be causing the pathologic changes that are associated with diabetic kidney disease (DKD). Higher serum SAA concentrations were previously associated with increased risk of end-stage renal disease (ESRD) and death in persons with type 2 diabetes and advanced DKD. We explored the prognostic value of SAA in American Indians with type 2 diabetes without DKD or with early DKD. <b><i>Methods:</i></b> SAA concentration was measured in serum samples obtained at the start of follow-up. Multivariate proportional hazards models were employed to examine the magnitude of the risk of ESRD or death across tertiles of SAA concentration after adjustment for traditional risk factors. The C statistic was used to assess the additional predictive value of SAA relative to traditional risk factors. <b><i>Results:</i></b> Of 256 participants (mean ± SD glomerular filtration rate [iothalamate] = 148 ± 45 mL/min, and median [interquartile range] urine albumin/creatinine = 39 [14-221] mg/g), 76 developed ESRD and 125 died during a median follow-up period of 15.2 and 15.7 years, respectively. After multivariable proportional hazards regression, participants in the 2 highest SAA tertiles together exhibited a 53% lower risk of ESRD (hazard ratio [HR] 0.47, 95% CI 0.29-0.78), and a 30% lower risk of death (HR 0.70, 95% CI 0.48-1.02), compared with participants in the lowest SAA tertile, although the lower risk of death was not statistically significant. Addition of SAA to the ESRD model increased the C statistic from 0.814 to 0.815 (<i>p </i>= 0.005). <b><i>Conclusions:</i></b> Higher circulating SAA concentration is associated with a reduced risk of ESRD in American Indians with type 2 diabetes.</p