Roles of plasma leptin and resistin in novel subgroups of type 2 diabetes driven by cluster analysis.

BACKGROUND: A novel classification has been introduced to promote precision medicine in diabetes. The current study aimed to investigate the relationship between leptin and resistin levels with novel refined subgroups in patients with type 2 diabetes mellitus (T2DM). METHODS: The k-means analysis was conducted to cluster 541 T2DM patients into the following four subgroups: mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild age-related diabetes (MARD). Individuals meeting the exclusion criteria were eliminated, the data for 285 patients were analyzed. Characteristics were determined using various clinical parameters. Both the leptin and resistin levels were determined using enzyme-linked immunosorbent assay. RESULTS: The highest levels of plasma leptin were in the MOD group with relatively lower levels in the SIDD and SIRD groups (P < 0.001). The SIRD group had a higher resistin concentration than the MARD group (P = 0.024) while no statistical significance in resistin levels was found between the SIDD and MOD groups. Logistic regression demonstrated that plasma resistin was associated with a higher risk of diabetic nephropathy (odds ratios (OR) = 2.255, P = 0.001). According to receiver operating characteristic (ROC) curves, the area under the curve (AUC) of resistin (0.748, 95% CI 0.610-0.887) was significantly greater than that of HOMA2-IR (0.447, 95% CI 0.280-0.614) (P < 0.05) for diabetic nephropathy in the SIRD group. CONCLUSIONS: Leptin levels were different in four subgroups of T2DM and were highest in the MOD group. Resistin was elevated in the SIRD group and was closely related to diabetic nephropathy.

High-dose dexamethasone suppression test is inferior to pituitary dynamic enhanced MRI in the differential diagnosis of ACTH-dependent Cushing's syndrome.

PURPOSE: The differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome remains a challenge in clinical practice. The present study was aimed at assessing the diagnostic performance of pituitary dynamic contrast-enhanced magnetic resonance imaging (dMRI), high-dose dexamethasone suppression test (HDDST), and a combination of both tests for patients with ACTH-dependent Cushing's syndrome. METHODS: A total of 119 consecutive patients with ACTH-dependent Cushing's syndrome confirmed surgically were enrolled: 101 with proven Cushing's disease and 18 with proven ectopic ACTH syndrome. All patients underwent pituitary dMRI and HDDST. The sensitivity and specificity of pituitary dMRI, HDDST, and a combination of both tests were determined. RESULTS: The sensitivity and specificity of pituitary dMRI for diagnosing Cushing's disease were 80.2 and 83.3%, respectively, with a positive predictive value of 96.4%. The sensitivity and specificity of HDDST were 70.3 and 77.8%, respectively, with positive predictive value of 94.7%. A combination of both tests showed that the combined criteria of more than 50% suppression of serum cortisol on HDDST and a positive pituitary dMRI finding yielded a high specificity of 94.4 and sensitivity of 59.4%. The combined criteria of more than 68% suppression on HDDST and/or a positive pituitary dMRI finding yielded a sensitivity of 86.1% and specificity of 83.3%. CONCLUSIONS: Pituitary dMRI was superior to HDDST in the differential diagnosis of ACTH-dependent Cushing's syndrome. HDDST is recommended in combination with pituitary dMRI to establish a diagnosis process because of the significantly increased specificity with the combination.

Association of ANGPTL8 and Resistin With Diabetic Nephropathy in Type 2 Diabetes Mellitus.

Background: Previous studies showed altered angiopoietin-like protein-8 (ANGPTL-8) and resistin circulating levels in type 2 diabetes mellitus (T2DM). Whether or not the alteration in ANGPTL-8 and resistin level can be a predictive maker for increased diabetic nephropathy risk remains unclear. Aim: To Investigate the possible association of ANGPTL-8 and resistin with DN, and whether this association is affected by NAFLD status. Methods: A total of 278 T2DM patients were enrolled. Serum levels of ANGPTL8, resistin, BMI, blood pressure, duration of diabetes, glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), hypersensitive C-reactive protein (hs-CRP), lipid profile, liver, and kidney function tests were assessed. The relationship between DN with ANGPTL8 and resistin was analyzed in the unadjusted and multiple-adjusted regression models. Results: Serum levels of ANGPTL8 and resistin were significantly higher in DN compared with T2DM subjects without DN (respectively; P <0.001), especially in non-NAFLD populations. ANGPTL8 and resistin showed positive correlation with hs-CRP (respectively; P<0.01), and negative correlation with estimated GFR (eGFR) (respectively; P=<0.001) but no significant correlation to HOMA-IR(respectively; P>0.05). Analysis showed ANGPTL8 levels were positively associated with resistin but only in T2DM patients with DN(r=0.1867; P<0.05), and this significant correlation disappeared in T2DM patients without DN. After adjusting for confounding factors, both ANGPTL8(OR=2.095, 95%CI 1.253-3.502 P=0.005) and resistin (OR=2.499, 95%CI 1.484-4.208 P=0.001) were risk factors for DN. Data in non-NAFLD population increased the relationship between ANGPTL8 (OR=2.713, 95% CI 1.494-4.926 P=0.001), resistin (OR=4.248, 95% CI 2.260-7.987 P<0.001)and DN. The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and resistin was 0.703, and the specificity was 70.4%. These data were also increased in non-NAFLD population, as the AUC (95%CI) was 0.756, and the specificity was 91.2%. Conclusion: This study highlights a close association between ANGPTL8, resistin and DN, especially in non-NAFLD populations. These results suggest that ANGPTL-8 and resistin may be risk predictors of DN.

Liver injury after intermittent or continuous hepatic pedicle clamping and its protection by reduced glutathione.

BACKGROUND: The debate is still going on about selection of several clamping patterns during hepatectomy. The aim of this study was to assess the safety and preference of normothermic intermittent or continuous hepatic pedicle clamping and confirm the protective effect of reduced glutathione (GSH). METHODS: Thirty-two adult male healthy Sprague-Dawley (SD) rats were divided into groups of intermittent clamping and GSH absent (IA), continuous clamping and GSH absent (CA), intermittent clamping and GSH present (IP) and continuous clamping and GSH present (CP). The clamping manners were successively 40 minutes in continuous clamping groups and two cycles of 20 minutes with an interval of 5 minutes in intermittent clamping groups, and reperfusion periods were 60 minutes. Experimental parameters included levels of malonaldehyde (MDA) and Cu/Zn superoxide dismutase (SOD), pathological and ultrastructural changes in liver tissues, activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in sera. RESULTS: In the same group, the activities of ALT and AST were significantly higher in post-clamping rats than in pre-clamping rats (P<0.05), but no significant differences were noted in levels of MDA and Cu/Zn SOD (P>0.05). The differences of all values between post-reperfusion rats and pre-clamping rats were significant (P<0.05). Pathological and ultrastructural changes could be observed, but no irreversible injury was present. The comparison of the groups showed that the values at relevant time points between the intermittent and continuous groups were not significantly different (P>0.05). The values were significantly different between the GSH absent and present groups after reperfusion (P<0.05). The morphological damages were also obviously alleviated in the GSH present group. CONCLUSIONS: Normothermic intermittent or continuous hepatic pedicle clamping could cause reversible liver ischemia/reperfusion injury when the clamping time lasts 40 minutes. The injury extent seems to be similar. Continuous clamping should be regarded as a proper method in liver surgery. GSH has been confirmed as an effective agent in preventing post-clamping liver injury.