Serum Amyloid A Truncations in Type 2 Diabetes Mellitus

Introduction Although high-density lipoprotein (HDL) is inversely correlated with cardiovascular risk, HDL loses its protective role in pathologic inflammatory states like type 2 diabetes (T2DM). HDL dysfunction contributes to accelerated atherosclerosis in T2DM, but the mechanism is incompletely defined. The acute phase reactant serum amyloid A (SAA) displaces apolipoprotein A-I and may impair HDL-mediated reverse cholesterol efflux. We hypothesized that SAA alters the inverse association between HDL and coronary artery calcium (CAC) in the Penn Diabetes Heart Study, a cross-sectional study of T2DM patients free of overt cardiovascular or renal disease. Methods We measured SAA in serum samples by immunonephelometry (N=975; mean age 58 ± 9 years; 63% male, 57% Caucasian; mean BMI 33 ± 6 kg/m 2 ). HDL was measured enzymatically in lipoprotein fractions after ultracentrifugation. Agatston CAC scores were quantified from electron beam tomography at the same visit. Spearman correlation and logistic regression were used to test associations of SAA with clinical factors and metabolic syndrome. We used Tobit regression to analyze associations between CAC and HDL, both overall and stratified by 3 categories of SAA: undetectable, lower half detectable, and upper half detectable. Results Spearman correlations revealed moderate association of SAA with C-reactive protein (r=0.52) and weak associations of SAA with BMI (r=0.25) and HDL (r=0.17; all p<0.001). In logistic regression, the group with highest SAA levels had increased odds of metabolic syndrome compared to those with undetectable levels (OR 1.56, 95% CI 1.03 to 2.38, p=0.036). In adjusted Tobit regression, HDL was inversely associated with CAC (Tobit coefficient for 1-SD increase in HDL: -0.30; 95% CI -0.54 to -0.06; p=0.013). Across the categories of SAA, however, there was no difference in the association of HDL with CAC (Tobit coefficient for 1-SD increase in HDL: -0.17 [95% CI -0.49 to 0.16] for undetectable vs. -0.31 [95% CI -0.79 to 0.17] for lower half detectable vs. -0.49 [95% CI -1.01 to 0.03] for upper half detectable). Conclusions Despite the association of SAA with metabolic syndrome, these data suggest that elevated SAA may not change the inverse relationship of HDL with CAC in T2DM.

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Acute-Phase Serum Amyloid A Protein and Its Implication in the Development of Type 2 Diabetes in the KORA S4/F4 Study

Diabetes Care ◽

10.2337/dc12-1514 ◽

2012 ◽

Vol 36 (5) ◽

pp. 1321-1326 ◽

Cited By ~ 19

Author(s):

C. Marzi ◽

C. Huth ◽

C. Herder ◽

J. Baumert ◽

B. Thorand ◽

...

Keyword(s):

Type 2 Diabetes ◽

Acute Phase ◽

Serum Amyloid A ◽

Serum Amyloid ◽

Amyloid A ◽

Serum Amyloid A Protein ◽

Acute Phase Serum

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A Relationship Between Alzheimer's Disease and Type 2 Diabetes Mellitus Through the Measurement of Serum Amyloid-β Autoantibodies

Journal of Alzheimer s Disease ◽

10.3233/jad-2010-1332 ◽

2010 ◽

Vol 19 (4) ◽

pp. 1371-1376 ◽

Cited By ~ 15

Author(s):

Insub Kim ◽

Junhee Lee ◽

Hyun Joo Hong ◽

Eun Sun Jung ◽

Yun Hyi Ku ◽

...

Keyword(s):

Diabetes Mellitus ◽

Alzheimer’S Disease ◽

Type 2 Diabetes ◽

Alzheimer's Disease ◽

Type 2 Diabetes Mellitus ◽

Amyloid Β ◽

Serum Amyloid

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Type 2 Diabetes in Young Females Results in Increased Serum Amyloid A and Changes to Features of High Density Lipoproteins in Both HDL2 and HDL3

Journal of Diabetes Research ◽

10.1155/2017/1314864 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Kayleigh Griffiths ◽

Agnieszka Pazderska ◽

Mohammed Ahmed ◽

Anne McGowan ◽

Alexander P. Maxwell ◽

...

Keyword(s):

Type 2 Diabetes ◽

Serum Amyloid A ◽

High Density ◽

Serum Amyloid ◽

Paraoxonase 1 ◽

High Density Lipoproteins ◽

Cvd Risk ◽

Young Females ◽

Amyloid A

Persons with type 2 diabetes mellitus (T2DM) have an elevated risk of atherosclerosis. High-density lipoproteins (HDL) normally protect against cardiovascular disease (CVD), but this may be attenuated by serum amyloid A (SAA). In a case-control study of young females, blood samples were compared between subjects with T2DM (n=42) and individuals without T2DM (n=42). SAA and apolipoprotein AI (apoAI) concentrations, paraoxonase-1 (PON-1), cholesteryl ester transfer protein (CETP), and lecithin-cholesterol acyltransferase (LCAT) activities were measured in the serum and/or HDL2 and HDL3 subfractions. SAA concentrations were higher in T2DM compared to controls: serum (30 mg/L (17, 68) versus 15 mg/L (7, 36); p=0.002), HDL2 (1.0 mg/L (0.6, 2.2) versus 0.4 mg/L (0.2, 0.7); p<0.001), and HDL3 (13 mg/L (8, 29) versus 6 mg/L (3, 13); p<0.001). Serum-PON-1 activity was lower in T2DM compared to that in controls (38,245 U/L (7025) versus 41,109 U/L (5690); p=0.043). CETP activity was higher in T2DM versus controls in HDL2 (232.6 μmol/L (14.1) versus 217.1 μmol/L (25.1); p=0.001) and HDL3 (279.5 μmol/L (17.7) versus 245.2 μmol/L (41.2); p<0.001). These results suggest that individuals with T2DM have increased SAA-related inflammation and dysfunctional HDL features. SAA may prove to be a useful biomarker in T2DM given its association with elevated CVD risk.

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