C-reactive protein/oxidised low-density lipoprotein/ß2-glycoprotein I complex promotes atherosclerosis in diabetic BALB/c mice via p38mitogen-activated protein kinase signal pathway.

BACKGROUND: The aim of this study was to investigate the effect of C-reactive protein/oxidised low-density lipoprotein/ß2-glycoprotein I (CRP/oxLDL/ß2GPI) complex on atherosclerosis (AS) in diabetic BALB/c mice. METHODS: BALB/c mice were fed high-fat and normal diet. Eight weeks later, the mice fed with high-fat diet were injected with streptozotocin (STZ) to induce diabetes. The diabetic mice were respectively injected twice monthly with 20 µg oxLDL, 20 µg ß2GPI, 40 µg oxLDL/ß2GPI complex, 44 µg CRP/oxLDL/ß2GPI complex, and PBS. Aortas were stained with Sudan IV to investigate lipid plaque formation. The infiltration condition of smooth muscle cells (SMCs), macrophages, and T cells in the aortas were determined by immunohistochemistry (IH). The mRNA expressions of receptors associated with lipid metabolism were quantified by real-time PCR. The phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and MKK3/6 in aorta tissues were assessed by Western blot. The expression of inflammation cytokines was evaluated by protein chip. RESULTS: The lipid plaques were more extensive, the lumen area was obviously narrower, the ratio of intima and media thickness were increased, and the normal internal elastic lamia structure and endothelial cell disappeared (P < 0.05) in the oxLDL and CRP/oxLDL/ß2GPI groups (P < 0.05). CRP/oxLDL/ß2GPI complex dramatically promoted infiltration of SMCs, macrophages, and T cells, improved the mRNA expression of ABCA1 and ABCG1, but reduced the mRNA expression of SR-BI and CD36 and increased the phosphorylation of p38MAPK and MKK3/6 (all P < 0.05). The highest expression levels of IL-1, IL-9, PF-4, bFGF, and IGF-II were detected in the CRP/oxLDL/ß2GPI group (P < 0.05). CONCLUSIONS: CRP/oxLDL/ß2GPI complex aggravated AS in diabetic BALB/c mice by increasing lipid uptake, the mechanism of which may be mediated by the p38MAPK signal pathway.

Health-related quality of life among Tianjin Chinese patients with type 2 diabetes: a cross-sectional survey.

The purpose of this study was to examine factors that influence the quality of life among Tianjin Chinese living with type 2 diabetes. In this study, the quality of life was assessed in 174 participants. The dependent variables included demographic and clinical data, depressive symptoms and lifestyle behavioral factors. Chi-square tests and logistic regression analysis were conducted to identify significant factors. Using multiple regression analyses, the odds ratios (ORs) of having low quality of life were 4.53 (95% confidence interval (CI) = 1.89-10.87), 2.83 (95% CI = 1.21-6.63), and 2.48 (95% CI = 1.03-5.96) for patients with microvascular complications, diabetic neuropathy, and peripheral vascular disease, respectively. Coronary heart disease, depression, and unhealthy eating habits were also found to have significant negative effects on quality of life. In addition, multiple regression analysis showed that regular exercise (OR = 0.29, 95% CI = 0.12-0.71) was a protective factor for health-related quality of life. The identification of these influencing factors will assist nurses to provide continuous care to people living with diabetes, thus to postpone or avoid complications as well as improve their quality of life.

Reliability and validity of the Chinese version of the new fear of hypoglycemia scale: FH-15.

OBJECTIVE: This study aimed to evaluate the reliability and validity of the Chinese version of the Fear of Hypoglycemia scale with 15 items (FH-15). METHODS: After obtaining the original author's authorization, the English version of the FH-15 scale was translated, back translated, and culturally debugged to obtain the Chinese version of FH-15. A convenient sampling method was used to extract patients with type 2 diabetes from four tertiary hospitals in Tianjin. A total of 408 patients with type 2 diabetes were investigated in the hospital to test the reliability and validity of Chinese version FH-15 scale. RESULTS: The content validity index of the scale was 0.92, and the content validity index of each item was 0.8-1.0. The exploratory factor analysis extracted three common factors (fear, avoidance, and interference), which contained 15 items, and the cumulative variance contribution rate was 71.245%. The confirmatory factor analysis results showed that the model fit was better at 1.981 χ 2/df, GFI = 0.901, CGI = 0.962, TLI = 0.952, and RMSEA = 0.070. The cut-off value for the total hypoglycemia fear scale was 30.5. The Cronbach's α coefficient of the three dimensions of the scale was 0.918, the Cronbach's α coefficient of each dimension is 0.876-0.916, the test-retest reliability was 0.903, and the test-retest reliability of each factor was 0.733-0.930. CONCLUSION: The Chinese version of the FH-15 scale can be considered reliable and valid. The item expression is concise, clear, and easy to understand. It is suitable for clinical practice as an initial screening tool to identify and evaluate the severity of fear of hypoglycemia in patients with type 2 diabetes.

[High D-glucose alters PI3K and Akt signaling and leads to endothelial cell migration, proliferation and angiogenesis dysfunction].

OBJECTIVE: To investigate the effects of high D-glucose on migration, proliferation, and angiogenesis of endothelial cells and to make sure whether PI3K and Akt signaling pathway plays an important role in the pathogenesis of diabetic vascular complications. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured. D-glucose of the concentrations of 5 mmol/L, 15 mmol/L, and 30 mmol/L and mannitol of the concentrations of 5 mmol/L, 15 mmol/L, and 30 mmol/L were added in to the medium, the migration rate of the cells was measured by wound healing test and the cell proliferation was examined with CellTiter 96 AQ(ueous) One Solution cell proliferation assay. Matrigel was spread on 96-well plate, and culture of HUVECs with D-glucose and mannitol of different concentrations were added. Microscopic photography was used to calculate the total area of vascular bed, average vessel length, vessel number, branch points, so as to observe the angiogenesis. Immuno-precipitation was used to detect the expression of p85/PI3K. Western blotting was used to detect the protein expression of p85/PI3K, p-PI3K, GSK3beta (downstream kinase of Akt), p-Akt (Threonine308) and p-GSK3beta. LY294002, a PI3K inhibitor, of the concentrations of 0.1 micromol/L, 1 micromol/L, and 10 micromol/L was added into the culture fluid with 5 mmol/L D-glucose, then the endothelial cell migration, proliferation number, total area of blood bed, etc were observed. RESULTS: The migration rate of the 5 mmol/L D-glucose group was 100 +/- 23/microm2, and D-glucose dose-dependently decreased the migration rate, e.g. the migration rates of the 15 mmol/L and 30 mmol/L D-glucose groups were 77 +/- 18/microm2 and 46 +/- 18/microm2 respectively, both significantly lower than that of the 5 mmol/L D-glucose group (both P < 0.01). LY294002 of the concentrations of 0.1 micromol/L, 1 micromol/L, and 10 micromol/L dose-dependently decrease the endothelial cells migration rates to 68 +/- 16/microm2, 36 +/- 12/microm2, and 13 +/- 3/microm2 respectively (all P < 0.01) The cell proliferation rate of the 5 mmol/L, 15 mmol/L) and 30 mmol/L D-glucose groups were 59,128 +/- 7415/well, 33,144 +/- 9082/well, and 11,625 +/- 4196/well respectively, showing that D-glucose dose-dependently decreased the cell proliferation (all P < 0.01). LY294002 of the concentrations of 0.1 micromol/L, 1 micromol/L, and 10 micromol/L dose-dependently decrease the endothelial cell proliferation to 42,560 +/- 4213/well, 17,688 +/- 7198/well, and 5704 +/- 558/well respectively (all P < 0.01). 15 mmol/L and 30 mmol/L D-glucose decreased the numbers of total area of vascular bed, average tubule length, number of capillaries, and number of vessel branch pint formed on the Matrigel. LY294002 dose-dependently inhibited the angiogenesis (P < 0.05 or P < 0.01) 15 mmol/L and 30 mmol/L D-glucose dose-dependently inhibited the phosphorylation of p85/P13K and Akt (P < 0.05 and P < 0.01). However, D-glucose did not influence the protein expression of p85/PI3K and Akt. Mannitol did not influence the cell proliferation, angiogenesis, and the expression of p85/PI3K, phosphorylated p85/PI3K, Akt, phosphorylated Akt (Thr308), and phosphorylated GSK3beta. CONCLUSION: Hyperglycemia-impaired PI3K-Akt signaling may lead to migration, proliferation and angiogenesis dysfunction of endothelial cells in diabetes patients, which is likely to contribute to the pathogenesis of diabetic vascular complications.