BACKGROUND: In this study, we identified the lipidomic predictors of early type 2 diabetic kidney disease (DKD) progression, which are currently undefined. METHODS: This longitudinal study included 92 American Indians with type 2 diabetes. Serum lipids (406 from 18 classes) were quantified using mass spectrometry from baseline samples when iothalamate-based glomerular filtration rate (GFR) was at least 90 mL/min. Affymetrix GeneChip Array was used to measure renal transcript expression. DKD progression was defined as at least 40% decline in GFR during follow-up. RESULTS: Participants had a mean age of 45 ± 9 years and median urine albumin/creatinine ratio of 43 (interquartile range 11–144). The 32 progressors had significantly higher relative abundance of polyunsaturated triacylglycerols (TAGs) and a lower abundance of C16–C20 acylcarnitines (ACs) ( P < 0.001). In a Cox regression model, the main effect terms of unsaturated free fatty acids and phosphatidylethanolamines and the interaction terms of C16–C20 ACs and short-low-double-bond TAGs by categories of albuminuria independently predicted DKD progression. Renal expression of acetyl-CoA carboxylase–encoding gene ( ACACA ) correlated with serum diacylglycerols in the glomerular compartment ( r = 0.36, and P = 0.006) and with low-double-bond TAGs in the tubulointerstitial compartment ( r = 0.52, and P < 0.001). CONCLUSION: Collectively, the findings reveal a previously unrecognized link between lipid markers of impaired mitochondrial β-oxidation and enhanced lipogenesis and DKD progression in individuals with preserved GFR. Renal acetyl-CoA carboxylase activation accompanies these lipidomic changes and suggests that it may be the underlying mechanism linking lipid abnormalities to DKD progression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00340678. FUNDING: NIH R24DK082841, K08DK106523, R03DK121941, P30DK089503, P30DK081943, and P30DK020572.

Human studies report conflicting results on the predictive power of serum lipids on the progression of chronic kidney disease. We aimed to systematically identify the lipids that predict progression to end-stage kidney disease. From the Chronic Renal Insufficiency Cohort, 79 patients with chronic kidney disease stages 2 to 3 who progressed to end-stage kidney disease over 6 years of follow-up were selected and frequency matched by age, sex, race, and diabetes with 121 nonprogressors with less than 25% decline in estimated glomerular filtration rate during the follow-up. The patients were randomly divided into training and test sets. We applied liquid chromatography-mass spectrometry-based lipidomics on visit year 1 samples. We identified 510 lipids, of which the top 10 coincided with false discovery threshold of 0.058 in the training set. From the top 10 lipids, the abundance of diacylglycerols and cholesteryl esters was lower, but that of phosphatidic acid 44:4 and monoacylglycerol 16:0 was significantly higher in progressors. Using logistic regression models, a multimarker panel consisting of diacylglycerols and monoacylglycerol independently predicted progression. The c-statistic of the multimarker panel added to the base model consisting of estimated glomerular filtration rate and urine protein-to-creatinine ratio as compared with that of the base model was 0.92 (95% confidence interval: 0.88–0.97) and 0.83 (95% confidence interval: 0.76–0.90, P < 0.01), respectively, an observation that was validated in the test subset. We conclude that a distinct panel of lipids may improve prediction of progression of chronic kidney disease beyond estimated glomerular filtration rate and urine protein-to-creatinine ratio when added to the base model.

Context: The association of hypoalbuminemia with osteoporosis in human studies is controversial. Objective: We tested the independent association between hypoalbuminemia and osteoporosis in a national dataset. Design: This is a cross-sectional observation. Setting and Participants: Participants are individuals selected from the National Health and Nutrition Examination Survey (NHANES) with available clinical, laboratory, and densitometry data from the 2005–2010 and 2013–2014 cycles. Exposure: Exposure is hypoalbuminemia defined as serum albumin <3.5 g/dL. Main Outcome Measure: Osteoporosis is defined as bone mineral density of ≤2.5 SD below the mean peak bone mass of young, healthy adults. Analysis took into account the hidden variance and the weighting methodology pertinent to analysis of NHANES. Results: Overall, 15 539 individuals were included. The mean age was 48.6 years (SE = 0.27). Fifty percent of the individuals were male, and 10.2% were of the black race. There was a graded decrease in the rate of osteoporosis from 15.2% at albumin 4 g/dL (P = .007) at the femoral neck and from 11.0 to 1.4% at total femur (P = .009). In a fully adjusted model, the odds of osteoporosis with hypoalbuminemia were 5.37-fold (95% confidence interval [CI], 1.43 to 20.20; P = .014) at the femoral neck, 12.46-fold (95% CI, 3.24 to 48.01; P < .001) at total femur, and 4.59-fold (95% CI, 1.49 to 14.16; P = .025) at the lumbar spine higher as compared to albumin >4 mg/dL. Conclusion: In the NHANES dataset, we report an independent association of osteoporosis with hypoalbuminemia at different anatomical sites.

Background: Population-based interventions aimed at halting the increasing prevalence of metabolic syndrome (MetS) require thorough understanding of dietary interplays. Objective is to identify the independent dietary nutrients associated with MetS and its components using dietary pattern identification and the single-nutrient approaches in The United States. Methods: This is a cross-sectional observation. Participants are selected from the National Health and Nutrition Examination Survey (NHANES) with available dietary intake, biochemical and anthropometrical data from 2001 to 2012. Exposure is diet obtained from 24-h dietary recall. Main outcome measure is MetS and its components. Results: Overall, 23 157 eligible individuals including 6561 with MetS were included in the final analysis. Using principle component analysis, we identified three food patterns that explained 50.8% of the variance of the dietary nutrient consumption. The highest quartile of the factor score representative of saturated/monounsaturated fatty acids or the first dietary pattern was associated with 1.27-fold (95% confidence interval (CI): 1.10–1.46, P=0.001) higher odds of association with MetS when compared with the first quartile. The second pattern representative of vitamins and trace elements had an odds ratio of 0.79 (95% CI: 0.70–0.89, P<0.001) for association with MetS, and the third pattern representative of polyunsaturated fatty acids did not have any association with MetS. The nutrient-by-nutrient approach showed that mild alcohol intake and lower consumption of total saturated fatty acids and sodium were associated with lower risk of MetS. Conclusions: Application of multiple complementary analytic approaches reveals more comprehensive dietary determinants of MetS and its components as potential intervening targets.

Context: Human studies have reported conflicting results on the association of hypoalbuminemia with osteoporosis. Objective: The aim of the study is to test the independent association between hypoalbuminemia and osteoporosis. Design: This is a cross-sectional observation. Setting and Participants: Patients are the outpatient consecutive individuals with available clinical, laboratory, and densitometry data from 2001 to 2013 in our tertiary care academic medical center. Exposure: Exposure is hypoalbuminemia defined as serum albumin less than 3.5 g/dL. Main Outcome Measure: Osteoporosis is defined as bone mineral density of 2.5 SD or less below the mean peak bone mass of young, healthy adults. Results: Overall, 21 121 patients were included. Mean of age was 61 years (SD 14). There were 4244 males (20.1%) and 1614 patients of African-American ethnicity (7.6%). There was a graded decrease in rate of osteoporosis from 28.0% (n = 33) at albumin of 3 g/dL or less to 9.3% (n = 1548) at albumin greater than 4 g/dL (P < .001) at the femoral neck and from 20.3% (n = 24) to 6.1% (n = 1011) at the total hip (P < .001). In a fully adjusted model, the odds of osteoporosis at albumin of 3 g/dL or less was 3.31-fold (95% confidence interval [CI] 2.08–5.28, P < .001) at the femoral neck, 2.98-fold (95% CI 1.76–5.01, P < .001) at the total hip, and 2.18-fold (95% CI 1.43–3.31, P < .001) at the lumbar spine as compared with albumin greater than 4 mg/dL. A similar independent association was identified with a longer-observed duration of hypoalbuminemia. Conclusion: In a large population, we report an independent association of osteoporosis with lower levels of serum albumin and a longer-observed duration of hypoalbuminemia.