Plasma CD36 and Incident Diabetes: A Case-Cohort Study in Danish Men and Women

다국어 초록 (Multilingual Abstract)

Background: Membrane CD36 is a fatty acid transporter implicated in the pathogenesis of metabolic disease. We aimed to evaluate the association between plasma CD36 levels and diabetes risk and to examine if the association was independent of adiposity among Danish population.
Methods: We conducted a case-cohort study nested within the Danish Diet, Cancer and Health study among participants free of cardiovascular disease, diabetes and cancer and with blood samples and anthropometric measurements (height, weight, waist circumference, and body fat percentage) at baseline (1993 to 1997). CD36 levels were measured in 647 incident diabetes cases that occurred before December 2011 and a total of 3,515 case-cohort participants (236 cases overlap).
Results: Higher plasma CD36 levels were associated with higher diabetes risk after adjusting for age, sex and other lifestyle factors.
The hazard ratio (HR) comparing high versus low tertile of plasma CD36 levels was 1.36 (95% confidence interval [CI], 1.00 to 1.86). However, the association lost its significance after further adjustment for different adiposity indices such as body mass index (HR, 1.23; 95% CI, 0.87 to 1.73), waist circumference (HR, 1.21; 95% CI, 0.88 to 1.68) or body fat percentage (HR, 1.20; 95% CI, 0.86 to 1.66). Moreover, raised plasma CD36 levels were moderately associated with diabetes risk among lean participants, but the association was not present among overweight/obese individuals.
Conclusion: Higher plasma CD36 levels were associated with higher diabetes risk, but the association was not independent of adiposity. In this Danish population, the association of CD36 with diabetes risk could be either mediated or confounded by adiposity.

참고문헌 (Reference)

• 1 World Health Organization, "Waist Circumference and Waist–Hip Ratio: Report of a WHO Expert Consultation"
• 2 Love-Gregory L, "Variants in the CD36 gene associate with the metabolic syndrome and high-density lipoprotein cholesterol" 17 : 1695-1704, 2008
• 3 Bonen A, "Triacylglycerol accumulation in human obesity and type 2 diabetes is associated with increased rates of skeletal muscle fatty acid transport and increased sarcolemmal FAT/CD36" 18 : 1144-1146, 2004
• 4 Bonen A, "The fatty acid transporter FAT/CD36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes" 30 : 877-883, 2006
• 5 Kelley DE, "Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance" 278 : E941-E948, 2000
• 6 Tjonneland A, "Study design, exposure variables, and socioeconomic determinants of participation in Diet, Cancer and Health : a population-based prospective cohort study of 57, 053 men and women in Denmark" 35 : 432-441, 2007
• 7 Koonen DP, "Soluble CD36-a marker of the(pathophysiological)role of CD36 in the metabolic syndrome" 117 : 57-63, 2011
• 8 Handberg A, "Soluble CD36(sCD36)clusters with markers of insulin resistance, and high sCD36 is associated with increased type 2 diabetes risk" 95 : 1939-1946, 2010
• 9 Glintborg D, "Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment" 31 : 328-334, 2008
• 10 Kunjathoor VV, "Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages" 277 : 49982-49988, 2002
• 11 Asakawa H, "Relationship of abdominal fat with metabolic disorders in diabetes mellitus patients" 55 : 139-149, 2002
• 12 Samovski D, "Regulation of insulin receptor pathway and glucose metabolism by CD36 signaling" 67 : 1272-1284, 2018
• 13 Elumalai S, "Rac1-NADPH oxidase signaling promotes CD36 activation under glucotoxic conditions in pancreatic beta cells" 11 : 126-134, 2017
• 14 Eckel RH, "Obesity and type 2 diabetes : what can be unified and what needs to be individualized" 96 : 1654-1663, 2011
• 15 Malhotra A, "Meta-analysis of genome-wide linkage studies of quantitative lipid traits in families ascertained for type 2 diabetes" 56 : 890-896, 2007
• 16 Glatz JF, "Membrane fatty acid transporters as regulators of lipid metabolism : implications for metabolic disease" 90 : 367-417, 2010
• 17 Payne R, "Kernel machine testing for risk prediction with stratified case cohort studies" 72 : 372-381, 2016
• 18 Sampson MJ, "Increased expression of a scavenger receptor(CD36)in monocytes from subjects with type 2 diabetes" 167 : 129-134, 2003
• 19 Liang CP, "Increased CD36 protein as a response to defective insulin signaling in macrophages" 113 : 764-773, 2004
• 20 Thunander M, "Incidence of type 1 and type 2 diabetes in adults and children in Kronoberg, Sweden" 82 : 247-255, 2008
• 21 Handberg A, "Identification of the oxidized low-density lipoprotein scavenger receptor CD36 in plasma : a novel marker of insulin resistance" 114 : 1169-1176, 2006
• 22 Aitman TJ, "Identification of Cd36(Fat)as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats" 21 : 76-83, 1999
• 23 World Health Organization, "Global Report on Diabetes"
• 24 An P, "Genome-wide linkage scans for fasting glucose, insulin, and insulin resistance in the National Heart, Lung, and Blood Institute Family Blood Pressure Program : evidence of linkages to chromosome 7q36 and 19q13 from meta-analysis" 54 : 909-914, 2005
• 25 Arya R, "Factors of insulin resistance syndrome : related phenotypes are linked to genetic locations on chromosomes 6 and 7 in nondiabetic Mexican-Americans" 51 : 841-847, 2002
• 26 Snel M, "Ectopic fat and insulin resistance : pathophysiology and effect of diet and lifestyle interventions" 2012 : 983814-, 2012
• 27 Rosner B, "Determination of blood pressure percentiles in normal-weight children : some methodological issues" 167 : 653-666, 2008
• 28 Norberg M, "Components of metabolic syndrome predicting diabetes : no role of inflammation or dyslipidemia" 15 : 1875-1885, 2007
• 29 Love-Gregory L, "Common CD36 SNPs reduce protein expression and may contribute to a protective atherogenic profile" 20 : 193-201, 2011
• 30 Heeboll S, "Circulating sCD36 levels in patients with non-alcoholic fatty liver disease and controls" 41 : 262-267, 2017
• 31 Khan S, "CD36 mediates lipid accumulation in pancreatic beta cells under the duress of glucolipotoxic conditions : novel roles of lysine deacetylases" 495 : 2221-2226, 2018
• 32 Zhang D, "CD36 gene variants is associated with type 2 diabetes mellitus through the interaction of obesity in rural Chinese adults" 659 : 155-159, 2018
• 33 Stegger JG, "Body composition and body fat distribution in relation to later risk of acute myocardial infarction : a Danish follow-up study" 35 : 1433-1441, 2011
• 34 Barlow WE, "Analysis of case-cohort designs" 52 : 1165-1172, 1999
• 35 American Heart Association, "About Metabolic Syndrome"
• 36 Griffin E, "A link between diabetes and atherosclerosis : glucose regulates expression of CD36 at the level of translation" 7 : 840-846, 2001