Insulin resistance levels predicted metabolic improvement and weight loss after metabolic surgery in Chinese patients with type 2 diabetes.

BACKGROUND: The causes for failure of metabolic improvement and inadequate weight loss after metabolic surgery (MS) in Chinese patients with type 2 diabetes (T2D) have not been fully elucidated. The effect of insulin resistance (IR) on the outcome of T2D, hypertension, hyperlipidemia, and obesity after MS in Chinese patients with T2D and a body mass index (BMI) of 25-32.5 kg/m2 warrants further study. OBJECTIVES: Patients with T2D and a BMI of 25-32.5 kg/m2 who underwent MS between July 2019 and June 2021 were included. SETTING: University hospital, China. METHODS: IR levels were evaluated with the glucose disposal rate (GDR). Improvement of T2D, hypertension, and hyperlipidemia was assessed with the composite triple endpoint (CTEP), and weight loss was assessed with the percent of total weight loss (%TWL). Partial correlation analysis, binary logistic regression analysis, multiple linear regression analysis, receiver operating characteristic curve (ROC) analysis, and subgroup analysis were used to analyze the relationship between the CTEP, %TWL at 1 year postoperative, and GDR preoperative. RESULTS: This study analyzed the data of 51 patients with T2D and a BMI of 25-32.5 kg/m2 (30 men and 21 women) with a mean preoperative GDR of 3.72 ± 1.48 mg/kg/min. Partial correlation coefficients between CTEP, %TWL, and GDR were .303 (P = .041) and .449 (P = .001), respectively. The preoperative GDR was significantly positively correlated with CTEP (OR = 1.610, P = .024) and %TWL (ß = 1.38, P = .003). The preoperative GDR predicted cutoff values of 4.36 and 5.35 mg/kg/min for CTEP attainment and %TWL ≥ 20%, respectively. CONCLUSION: IR levels predicted metabolic improvement and weight loss 1 year after MS in Chinese patients with T2D and a BMI of 25-32.5 kg/m2.

Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer.

The inhibitor of apoptosis protein survivin has a critical regulatory role in carcinogenesis and treatment tolerance in colorectal cancer (CRC). However, the targeted drugs for survivin protein are extremely limited. In the present research, we discovered that Tanshinone IIA (Tan IIA) played a dual regulatory role in inhibiting tumorigenesis and reversing 5-Fu tolerance via modulating the expression and phosphorylation of survivin in CRC cells. Mechanistically, Tan IIA suppressed the Akt/WEE1/CDK1 signaling pathway, which led to the downregulation of survivin Thr34 phosphorylation and destruction of the interaction between USP1 and survivin to promote survivin ubiquitination and degradation. Furthermore, Tan IIA significantly facilitated chemoresistant CRC cells to 5-Fu sensitivity. These results revealed that Tan IIA possessed a strong antitumor activity against CRC cells and could act as an up-and-coming agent for treating CRC and overcoming chemotherapy resistance.

Transcriptome-wide association study-derived genes as potential visceral adipose tissue-specific targets for type 2 diabetes.

AIMS/HYPOTHESIS: This study aimed to assess the causal relationship between visceral obesity and type 2 diabetes and subsequently to screen visceral adipose tissue (VAT)-specific targets for type 2 diabetes. METHODS: We examined the causal relationship between VAT and type 2 diabetes using bidirectional Mendelian randomisation (MR) followed by multivariable MR. We conducted a transcriptome-wide association study (TWAS) leveraging prediction models and a large-scale type 2 diabetes genome-wide association study (74,124 cases and 824,006 controls) to identify candidate genes in VAT and used summary-data-based MR (SMR) and co-localisation analysis to map causal genes. We performed enrichment and single-cell RNA-seq analyses to determine the cell-specific localisation of the TWAS-identified genes. We also conducted knockdown experiments in 3T3-L1 pre-adipocytes. RESULTS: MR analyses showed a causal relationship between genetically increased VAT mass and type 2 diabetes (inverse-variance weighted OR 2.48 [95% CI 2.21, 2.79]). Ten VAT-specific candidate genes were associated with type 2 diabetes after Bonferroni correction, including five causal genes supported by SMR and co-localisation: PABPC4 (1p34.3); CCNE2 (8q22.1); HAUS6 (9p22.1); CWF19L1 (10q24.31); and CCDC92 (12q24.31). Combined with enrichment analyses, clarifying cell-type specificity with single-cell RNA-seq data indicated that most TWAS-identified candidate genes appear more likely to be associated with adipocytes in VAT. Knockdown experiments suggested that Pabpc4 likely contributes to regulating differentiation and energy metabolism in 3T3-L1 adipocytes. CONCLUSIONS/INTERPRETATION: Our findings provide new insights into the genetic basis and biological processes of the association between VAT accumulation and type 2 diabetes and warrant investigation through further functional studies to validate these VAT-specific candidate genes.

Progress in the study of intragastric occupancy device for weight reduction. / èƒƒå† å å®¹è£ ç½®å‡é‡çš„ç ”ç©¶è¿›å±•.

Obesity is a global public health problem that imposes a heavy economic burden on society. The current main strategies for treating obesity include lifestyle interventions, pharmacological treatments, endoscopic treatments and metabolic surgery. With the development of medical technology, weight reduction by intragastric occupancy devices represented by intragastric balloons and intragastric capsules are gradually emerging. Intragastric balloons are used to reduce weight by occupying the volume of the stomach with balloons filled with different volumes of gas or liquid, among which ReShape, Orbera, Obalon, Elipse and Spatz balloons are gradually used in patients with mild to moderate obesity due to their non-invasive, high safety and reusable advantages. Intragastric capsules are recommended in overweight and obese patients for weight loss through hydrogels with transient superabsorbent swelling properties and completely noninvasive. Both approaches achieve weight loss by limiting gastric volume, increasing satiety and reducing food intake. Despite the presence of adverse gastrointestinal events associated with nausea, vomiting, and abdominal distention, they offer new ideas for the non-invasive clinical treatment of obesity.

TyG Index Performs Better Than HOMA-IR in Chinese Type 2 Diabetes Mellitus with a BMI < 35 kg/m2: A Hyperglycemic Clamp Validated Study

Background and objectives: Chinese type 2 diabetes mellitus (T2DM) patients are characterized by a low body mass index (BMI), and significant insulin resistance (IR). The triglyceride glucose (TyG) index has not been studied as a means of assessing IR in Chinese T2DM patients with a BMI < 35 kg/m2. Materials and Methods: An open-label cross-sectional study recruited 102 Chinese T2DM patients with a BMI < 35 kg/m2. The hyper-insulinemic euglycemic clamp, homeostatic model assessment of IR (HOMA-IR), and TyG index were used to determine the level of IR. Based on Pearson's correlations, glucose disposal rate (GDR), TyG index, and HOMA-IR were analyzed. HOMA-IR and TyG index for IR were evaluated using multiple linear regression and multivariate logistic regression analyses. On the basis of the receiver operating characteristic (ROC) curve, the sensitivity, specificity, and optimal cut-off value of HOMA-IR and the TyG index were determined. Results: The mean values of GDR, HOMA-IR, and TyG index were 4.25 ± 1.81, 8.05 ± 7.98, and 8.12 ± 0.86 mg/kg/min, respectively. Pearson's correlation coefficient was −0.418 between GDR and TyG index and −0.324 between GDR and HOMA-IR. ROC curve analysis showed that, among both sexes, the TyG index was a better discriminator of IR than HOMA-IR. The area under the ROC curve (AUC) of the TyG index (0.785, 0.691−0.879) was higher than that of HOMA-IR (0.73, 0.588−0.873) in all genders. The optimal cut-off values of the TyG index and HOMA-IR were 7.99 and 3.39, respectively. Conclusions: The TyG index showed more effectiveness in identifying IR in Chinese T2DM patients with a BMI < 35 kg/m2 compared to HOMA-IR.

Insulin Resistance Remission Following Laparoscopic Roux-en-Y Gastric Bypass and Laparoscopic Sleeve Gastrectomy in Chinese Type 2 Diabetes Mellitus Patients With a Body Mass Index of 27.5-32.5 kg/m2.

Background: Insulin resistance (IR) is closely associated with the pathogenesis of type 2 diabetes mellitus (T2DM). However, remission of insulin sensitivity after bariatric surgery in patients with T2DM and a body mass index (BMI) of 27.5-32.5 kg/m2 has not been fully elucidated. Methods: Thirty-six T2DM patients with a BMI of 27.5-32.5 kg/m2 were prospectively consecutively recruited for laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG). Hyperinsulinemic euglycemic clamp, oral glucose tolerance test (OGTT), and other indicators were tested at baseline and 6 months postoperative. Glucose disposal rate (GDR), time to reach euglycemia, homeostatic model assessment of IR, quantitative insulin sensitivity check index (QUICKI), triglyceride glucose (TyG) index, 30-min insulinogenic index (IGI30), and disposition index (DI) were calculated at baseline and 6 months after surgery. The criterion for remission in T2DM patients was the achievement of the triple composite endpoint. Results: Anthropometric and glucolipid metabolism parameters significantly improved following surgery. The GDR increased significantly from baseline to 6 months after LRYGB (from 4.28 ± 1.70 mg/kg/min to 8.47 ± 1.89 mg/kg/min, p < 0.0001) and LSG (from 3.18 ± 1.36 mg/kg/min to 7.09 ± 1.69 mg/kg/min, p < 0.001). The TyG index decreased after surgery (RYGB group, from 9.93 ± 1.03 to 8.60 ± 0.43, p < 0.0001; LSG group, from 10.04 ± 0.79 to 8.72 ± 0.65, p = 0.0002). There was a significant reduction in the IGI30 (RYGB group, from 2.04 ± 2.12 to 0.83 ± 0.47, p = 0.005; LSG group, from 2.12 ± 1.73 to 0.92 ± 0.66, p = 0.001). The mean DI significantly increased from 1.14 ± 1.35 to 7.11 ± 4.93 in the RYGB group (p = 0.0001) and from 1.25 ± 1.78 to 5.60 ± 4.58 in the LSG group (p = 0.003). Compared with baseline, HOMR-IR, QUICKI, area under the curve-C-peptide release test (AUC-CRT), and AUC-OGTT were significantly changed at 6 months postoperative. Overall, 52.63% of patients in the LRYGB group versus 29.41% of patients in the LSG group achieved the triple composite endpoint. Conclusion: Both LRYGB and LSG effectively induced remission of IR in patients with T2DM and a BMI of 27.5-32.5 kg/m2.