[Effect of iron overload on the level of carbohydrate antigen 199 in type 2 diabetes mellitus].

Objective: To investigate the effect of iron overload on tumor marker CA199 in patients with type 2 diabetes mellitus (T2DM). Methods: Between January 2017 and June 2018, three hundred and twenty-three hospitalized patients with T2DM in Department of Endocrinology, Tianjin Fourth Central Hospital were selected as diabetes group and another 100 healthy persons as control group. All the participants with major diseases and factors affecting serum ferritin and CA199 level were excluded. Serum ferritin and CA199 levels were measured by chemiluminescence assay. Patients with a ferritin level above the normal range were defined as iron overload group. According to serum ferritin level, 178 patients were divided into iron overload group and 145 into normal ferritin group in the diabetes group. The levels of CA199 were compared between iron overload group and normal ferritin group, and the correlation was analyzed. Results: The levels of serum ferritin [407.1 (346.7) µg/L vs 266.6 (201.1) µg/L in males, 184.7 (133.0) µg/L vs 77.4 (64.0) µg/L in females,both P<0.001] and CA199 [18.2 (19.3) µg/L vs 9.3 (9.7) µg/L, P<0.001] in diabetes group were significantly higher than those in control group. Serum CA199 levels in iron overload group were significantly higher than those in normal ferritin group (20.7 µg/L vs 15.0 µg/L, P<0.001; above intermediate value percent:53.9% vs 35.8%,P=0.001). CA199 was positively correlated with glycosylated hemoglobin (HbA1c) (r=0.280, P<0.001) and iron overload (r=0.210, P<0.001). Multiple linear regression analysis showed that iron overload (ß'=0.203, P=0.002) and HbA1c (ß(')'=0.202, P=0.001) had a significant effect on CA199 level. Conclusion: In T2DM patients, iron overload is an important factor affecting serum CA199 level.

[Effect of telmisartan on peroxisome proliferator-activated receptor γ signaling pathway in 3T3-L1 adipocytes].

Objective: To investigate the mechanisms of telmisartan on delaying the course of type 2 diabetes. Methods: 3T3-L1 preadipocytes were induced to 80% mature adipocytes (control group) and stimulated with 50 ng/ml tumor necrosis factor (TNF-α) for 1 hour (TNF-α group). Then 0.1, 5, 10 µmol/L telmisartan was added to the culture medium for 24 h, respectively(T(0.1, )T(5) and T(10) group). The cells from each group was collected to detect peroxisome proliferator-activated receptors γ (PPARγ) and its phosphorylation level, as well as upstream kinase cell cycle dependent kinase 5 (CDK5) by Western blot. Adiponectin in the culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA). PPARγ or CDK5 of undifferentiated 3T3-L1 adipocytes were silenced by using targeted short hairpin RNA (shRNA). Through infection of the cells with the retrovirus, stabled PPARγ or CDK5 knockdown cell lines were set up and screened by incubation with puromycin. 3T3-L1 adipocyte cell lines expressing serine mutant PPARγ (S273A, S112A, S186A) were obtained and thus their phosphorate sites were further determined. CDK5 knockdown cell lines were detected by oil red O staining to measure the lipid accumulation and differentiation efficiency. The 10 µmol/L telmisartan was used to treat mature CDK5 knockdown 3T3-L1 adipocytes, Western blot was used to detect PPARγ and its phosphorylation level, and ELISA was used to detect the release of adiponectin in the culture supernatant. Results: The TNF-α stimulation had no significant effect on the expression of PPARγ in each group (all P>0.05), but it could up-regulate the phosphorylation of PPARγ in the TNF-α group and down-regulate the release of adiponectin (all P<0.05). Compared with TNF-α group, telmisartan can reduce PPARγ phosphorylation levels and up-regulate adiponectin release in different degrees, among which T(5) group and T(10) group had statistically significant differences (all P<0.05), but for T(0.1) group, the difference was not significant (P>0.05). Compared with the 3T3-L1 wild type (WT) adipocytes, adiponectin in cell line with only S273A mutant did not respond to TNF-α stimulation and telmisartan intervention. Oil red O staining showed that silencing of CDK5 did not affect the differentiation of 3T3-L1 preadipocytes. Western blot results showed that silencing of CDK5 (shCDK5 group) had no significant effect on PPARγ expression (P>0.05), but it could down-regulate the phosphorylation of PPARγ and up-regulate release of adiponectin, compared with the randomized control group (shCon group) and the differences were statistically significant (all P<0.05). Conclusions: Telmisartan can alleviate the increased PPARγ phosphorylation and up-regulation of adiponectin content due to TNF-α stimulation. CDK5 mediates the effect of telmisartan on PPARγ signaling pathway in 3T3-L1 adipocytes. Additonally, it also demonstrated the action site of telmisartan was PPARγ Ser 273, and CDK5 is upstream kinases of PPARγ.

[Effect of biofeedback therapy on metabolic syndrome under different levels of job stress].

Objective: To investigate the effect of biofeedback therapy on metabolic syndrome (MS) and the effect of different levels of job stress on the outcome. Methods: The physicians in tertiary hospitals who were diagnosed with MS from January to December, 2016 were divided into biofeedback group and health education group according to different intervention methods, and moderate group, medium group, and high group according to different levels of job stress. A 6-month intervention was implemented from May to October, 2017. A two-way factorial design was used to analyze the main effect of biofeedback on physical and biochemical parameters and the interaction of biofeedback and job stress. Results: After 6 months of intervention, the patients in both the biofeedback group and the moderate group had significantly decreased waist circumference, body mass index, systolic blood pressure (SBP) , diastolic blood pressure (DBP) , and levels of triglyceride (TG) , total cholesterol, low-density lipoprotein cholesterol (LDL-C) , and fasting plasma glucose (FPG) and a significantly increased level of high-density lipoprotein cholesterol (HDL-C) (all P<0.05) ; the patients in both the health education group and the moderate group had significantly decreased SBP, DBP, and levels of TG, LDL-C, and FPG (P<0.05) . The factorial analysis of variance showed that there was a synergistic interaction between the intervention method and job stress level in SBP, DBP, TG, HDL-C, LDL-C, and FPG among MS patients (P<0.05) . The high group had significantly more improvements in all indices compared with the medium group and the moderate group (P<0.05) . Conclusion: Biofeedback therapy can effectively improve blood pressure, blood lipids, and blood glucose in MS patients, and is more effective for patients with high job stress level.

[Effect of probucol on preventing contrast-induced nephropathy in patients undergoing percutaneous coronary intervention].

Objective: To investigate the preventive effect, possible mechanism and safety of probucol on contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). Methods: A total of 641 patients with coronary heart disease were consecutively enrolled from Department of Cardiology, in Tianjin Chest Hospital, Tianjin TEDA International Cardiovascular Hospital, Tianjin First Central Hospital, Tianjin Fourth Central Hospital. They were randomly divided into probucol group (n=321) and control group (n=320). The probucol group was given oral probucol 500 mg twice daily for day 0 to day 3 after PCI; the control group was given only conventional therapy. All patients were given intravenous drip 0.9% sodium chloride solution before 12 to 24 hours of operation. The levels of serum creatinine (Scr), blood urea nitrogen (BUN), evaluate glomerular filtration rate (eGFR), cystatin C (Cys-C), and high-sensitivity C-reactive protein (hs-CRP), neutrophil gelatinase associated lipocalin (NGAL), superoxide dismutase (SOD) and glutathione (GSH) were measured before and 72 h after the PCI operation in both groups. The incidence rates of CIN, the adverse events during hospitalization and postoperative 14-day follow-up were recorded in two groups. Results: There was no statistically significantly difference in the levels of Scr, BUN, eGFR, Cys-C, hs-CRP, NGAL, SOD and GSH between the two groups before PCI (P>0.05). The levels of serum Scr, BUN, Cys-C, hs-CRP, NGAL, SOD and GSH after operation in the two groups were higher than those before the operation (P<0.05). The levels of hs-CRP and NGAL in the probucol group were lower than those in the control group [(10±4) vs (11±4)mg/L, (25±8)vs (34±7)U/ml, P<0.05]. The levels of eGFR, SOD and GSH in probucol group were higher than those in control group [(80±27) vs (72±26) ml·min(-1)·1.73 m(-2,) (67±9) vs (58±8)U/ml, (4.6±0.9) vs (3.9±0.8)U/ml, P<0.05]. The incidence of CIN was 4.0% in the probucol group and 10.9% in the control group, and the difference was statistically significant (P<0.05, χ(2)=-3.31). Multivariate Logistic regression analysis showed that probucol was an independent protective factor for CIN (OR=0.334, 95%CI 0.172-0.648, P=0.001). There were no adverse events such as myasthenia gravis, abnormal liver function and cardiovascular events during the hospitalization and 14-day follow-up. Conclusions: Probucol can reduce the incidence of contrast-induced nephropathy after PCI. The protection mechanism is related with its anti-inflammatory and anti-oxidative stress effects, and it has good safety.

A targeted metabolomic profiling of plasma acylcarnitines in nonalcoholic fatty liver disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) has become a common liver disorder caused by lipid accumulation and insulin resistance (IR). Acylcarnitines have become a new biomarker of IR. However, their roles in NAFLD are still poorly studied. Thus, we performed a targeted metabolomic analysis to study the level of plasma acylcarnitines in patients with NAFLD. MATERIALS AND METHODS: The levels of 34 plasma acylcarnitines were measured by a targeted metabolomic approach in NAFLD patients (n = 50) and in healthy control subjects (n = 50) by liquid chromatography-tandem mass spectrometry. Detailed demographic and clinical characteristics of all subjects were also analyzed. RESULTS: The clinical presentation of IR was identified in the NAFLD group but not in the healthy control group. Significant differences were found in the levels of several short-, medium- and long-chain acylcarnitines. A high degree of correlation (r>0.7) was found between even-numbered-carbon long-chain acylcarnitines in NAFLD patients. The area under the receiver operator characteristic of long-chain acylcarnitines, especially C20 (AUC=0.952), C16:1 (AUC=0.949) and C14:1OH (AUC=0.944) acylcarnitines, was greater in NAFLD patients than in healthy control subjects. CONCLUSIONS: The accumulation and disorders of acylcarnitines are associated with NAFLD. A positive correlation between even-numbered-carbon long-chain acylcarnitines was found, and these even-numbered-carbon long-chain acylcarnitines. could be used as potential novel screening markers for nonalcoholic fatty liver disease.

Psychological distress and type 2 diabetes mellitus: a 4-year policemen cohort study in China.

OBJECTIVES: This study investigated whether psychological distress predicts the development of type 2 diabetes mellitus (T2DM) and if the association differs between populations at a high or low diabetes risk level among Chinese police officers. DESIGN: Prospective cohort study. SETTING: Single centre. PARTICIPANTS: 6559 participants underwent clinical measurements at the hospital in April 2007. 5811 police officers participated in the follow-up consisting of new-onset diabetes (NOD) events occurring annually between 2008 and 2011. PRIMARY OUTCOME MEASURES: Baseline data were collected from policemen who completed the Symptom Checklist 90-Revised (SCL-90-R) questionnaire and a self-designed questionnaire. Psychological distress was measured by the SCL-90-R questionnaire. Hong Kong Chinese Diabetes Risk Score (HKCDRS) was used to evaluate the risk of T2DM, and the participants were divided into low-risk group and high-risk group based on the HKCDRS. Cox proportional hazards regression was used to calculate the HRs of the incidence of T2DM related to psychological distress and further stratified the analysis based on HKCDRS. RESULTS: Among 5811 participants, 179 subjects developed NOD during the 4-year follow-up. 54 subjects (1.63%) with a HKCDRS 0-7 vs 125 subjects (4.98%) with a HKCDRS>7 developed NOD (p<0.05). There was a significant association between psychological distress and T2DM (HR=1.46; 95% CI 1.05 to 2.02). Among the participants with a high-risk score (HKCDRS>7), 7.07% of those with psychological distress developed T2DM compared with 4.43% of participants without psychological distress (p<0.05). The corresponding adjusted HR for psychological distress was 1.61 (95% CI 1.10 to 2.37). CONCLUSIONS: Psychological distress is an independent risk factor for T2DM in this prospective cohort study. Stratification analysis indicated that psychological distress was associated with T2DM in a high-risk level population.