Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy最新文献

Background: Several lipid metabolism-related profiles have been explored for their association with obesity, but no consensus has been reached. Therefore, this study aimed to comprehensively analyze the correlation between conventional and unconventional lipid profiles and visceral fat area (VFA) in overweight/obese patients with type 2 diabetes mellitus (T2DM). Emphasizing the overall relationship between lipid metabolism and visceral fat accumulation.

Methods: This cross-sectional study included 1288 overweight/obese T2DM patients, with VFA measured using bioelectrical impedance analysis and visceral fat obesity (VFO) was defined as VFA ≥ 100 cm². Both conventional lipid profiles include total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and lipoprotein(a), and unconventional lipid profiles include lipid composite index (LCI), platelet/ HDL-c ratio (PHR), remnant cholesterol (RC), TG/HDL-c, Castelli Risk Index I (CRI-I), Castelli Risk Index II (CRI-II), Non-HDL-c, atherogenic index of plasma (AIP) and atherogenic coefficient (AC) were analyzed. The study population was divided into non-VFO and VFO groups, The relationship between conventional and unconventional lipid profiles and VFO was evaluated.

Results: Compared to the non-VFO group, the VFO group exhibited significantly higher levels of TG, lipoprotein(a), LCI, RC, TG/HDL-c, CRI-I, CRI-II, AIP, and AC (all P < 0.05). Univariate analysis revealed that RC, TG, LCI, TG/HDL-c, CRI-I, CRI-II, AIP, and AC were positively correlated with VFA and VFO, while HDL-c and lipoprotein(a) were negatively correlated (all P < 0.05). Logistic regression identified RC as an independent risk factor for VFO (OR: 1.667, 95% CI: 1.216-2.285, P = 0.001).

Conclusion: Among lipid profiles, RC is independently and significantly associated with VFO, underscoring its role in lipid metabolism and abdominal obesity management, especially in overweight/obese T2DM patients.

Background: Normal weight obesity (NWO) is defined as normal body mass index (BMI) but increased body fat percentage (BF%). NWO population tend to develop metabolic syndrome, type 2 diabetes and cardiovascular disease. BF% is the key parameter applied in the evaluation of NWO. The exact prevalence of NWO and the cutoff point for the diagnosis of NWO are not well established. Diet and physical activity interventions are the main approach for NWO management. Smartphone apps are widely used for their effectiveness and individualization, making them ideal tool for simplifying the follow-up process in behavioral interventions for both investigators and participants.

Methods: A single center, prospective, randomized trial will be conducted in Beijing, China. The aim of this 12-week trial is to assess the efficacy of different lifestyle interventions, including diet control only, aerobic training only, resistance training only, and a combination of aerobic and resistance training based on a smartphone app on BF% and metabolic parameters in the NWO population. The primary outcome is the change of BF% between the baseline and 12 weeks post-intervention. The secondary outcomes include changes in measures of anthropometry, blood glucose, insulin, lipids and uric acid between the baseline and 12 weeks of intervention. A sample size of 200 subjects with normal BMI and glucose abnormality confirmed by oral glucose tolerance test will be recruited. Two follow-ups face-to-face and five follow-ups via smartphone app will be included in this trial. Statistical analyses will focus on the differences among different lifestyle interventions and the cutoff point of BF% for diagnosis of NWO.

Discussion: This trial will provide evidence of the efficacy of lifestyle interventions based on smartphone app. The differences in effect among different lifestyle intervention groups will be elucidated. It will be helpful to propose the cutoff point of BF% for diagnosis of NWO.

Trial registration number: This study was registered with chictr.org.cn: ChiCTR2200063583.

Objective: The annual incidence of overweight or obesity and abnormally elevated blood glucose levels in China is increasing. According to research, diacylglycerol oil offers effective lipid-lowering and weight-loss properties. This study aimed to elucidate the effects of diacylglycerol oil on overweight and obese patients with unusually high blood glucose levels.

Methods: This is a single-arm trial. A total of 75 overweight or obese subjects with abnormally elevated blood glucose levels were included in this study. Subjects were requested to use diacylglycerol oil to cook food daily for two months and to maintain their daily eating habits and drug treatment regimen. Study-related parameters were assessed, respectively, during the screening period, one month, and two months following DAG oil consumed.

Results: Fasting blood glucose (FBG), body weight, body mass index (BMI), waist circumference, and hip circumference decreased compared with baseline after consuming diacylglycerol oil for two months. FBG and glycosylated hemoglobin (HbAlc) levels decreased in prediabetic subjects (FBG decreased at visit 2 months: -0.31 mmol/l; at visit 1 month: -0.28 mmol/l; HbAlc decreased at visit 2: -0.10%; P < 0.05), but there were no significant difference changes in diabetic subjects. In diabetic participants, triglyceride (TAG) levels reduced by 0.17 mmol/l, whereas in prediabetic subjects, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels decreased by 0.27 mmol/l and 0.28 mmol/l, respectively (P < 0.05). There were no significant differences in the changes in high-density lipoprotein cholesterol (HDL-C) and uric acid (UA) between two groups. Compared to baseline, diabetic participants' body weight, BMI, and waist-to-hip ratio (WHR) dropped by 0.54 kg, 0.20, and 0.01 kg, respectively (P < 0.05). And prediabetic participants' BMI, waist circumference, and hip circumference dropped by 0.43, 1.43, and 1.53 cm, respectively (P < 0.05).

Conclusion: Diacylglycerol oil may help to prevent diabetes and delays its progression in overweight or obese patients.

Clinical trial registry: ChiCTR2000028888 at www.chictr.org.cn.

Context: Shengmai San (SMS) is a traditional Classic Recipes made with Panax ginseng, Ophiopogon, and Schisandra. The precise mechanism of action of SMS remains unclear, despite its noteworthy therapeutic advantages for type 2 diabetes mellitus (T2DM).

Objective: The objective of this study was to confirm the mechanism of SMS in the treatment of T2DM.

Materials and methods: UPLC-MS/MS was employed to identify the active components in SMS. Using network pharmacology, the intervention pathways of SMS in T2DM rats were investigated. A high-sugar, high-fat diet and intrabitoneal injection of streptozotocin were used to create a T2DM rat model. The serum parameters of each group were assessed following the completion of the experiment. The mRNA and protein expression levels of genes related to the PI3K/AKT/GSK3B pathway were analyzed using qRT-PCR and Western blot.

Results: There were 39 components found in SMS San by UPLC-Q-Orbitrap/MS. Network pharmacology and molecular docking study indicate that the PI3K/AKT/GSK3B pathway may be a part of SMS's therapeutic mechanism for the treatment of T2DM. Rats' serum levels of TC, TG, LDL-C, MDA, TNF-α, and IL-6 dramatically dropped after taking SMS, whereas SOD and HDL-C levels rose. The improvement of these parameters may be related to SMS activation of downstream target proteins, PI3K, and AKT.

Conclusion: SMS can help cure T2DM mellitus by regulating the PI3K/AKT/GSK3B pathway, improving islet tissue injury, reducing oxidative stress, and easing lipid metabolism issues. This study not only revealed the unique therapeutic mechanism of SMS by regulating the PI3K/AKT/GSK3β signaling pathway, but also provided new theoretical support for multi-target and personalized treatment of diabetes. Its novelty lies in the first exploration of the mechanism of action of traditional Chinese medicine prescriptions through the lens of modern molecular biology, emphasizing the potential of natural medicines in diabetes treatment.

Introduction: Sphingolipid metabolism has been implicated in many diseases including cancer, pathologic inflammation, viral infection, neurologic pathologies and metabolic pathologies, including obesity and diabetes. We have previously shown that opaganib (aka ABC294640) inhibits three key enzymes in the sphingolipid metabolism pathway: sphingosine kinase-2, dihydroceramide desaturase and glucosylceramide synthase. We and others have demonstrated anticancer, anti-inflammatory and antiviral activities of opaganib in multiple experimental models. Furthermore, opaganib has been studied in clinical trials with patients having cancer or severe Covid-19. In the present studies, the effects of opaganib in the well-established model of High-Fat Diet (HFD)-induced obesity have been studied.

Methods: Male or female C57BL/6 mice were fed Control Diet (CD) or HFD and treated with vehicle or opaganib by oral gavage once daily, 5 days per week. Body weights were monitored and glucose tolerance was measured periodically for up to 16 weeks. In some experiments, obese HFD-fed mice were treated with vehicle, opaganib alone, semaglutide alone or opaganib plus semaglutide.

Results: Treatment with opaganib markedly suppressed weight gain in male mice fed the HFD but not in mice given the CD. Compared with mice given CD, mice on the HFD demonstrated poor glucose tolerance at 8, 12 and 16 weeks, consistent with the progression of obesity. Importantly, opaganib treatment of the HFD-fed mice abolished this developing glucose intolerance at all times of measurement. Opaganib treatment also reduced the elevation of hemoglobin A1c and the deposition of inguinal fat in HFD-fed mice. Similar results were obtained with female mice, indicating equivalent efficacy of opaganib in both sexes. Additionally, opaganib and semaglutide were equally effective in promoting body weight loss and improving glucose tolerance in obese mice. Opaganib administered either concurrently with semaglutide or as a single drug following cessation of semaglutide treatment eliminated weight rebound.

Conclusion: Overall, the data indicate that opaganib effectively suppresses the loss of metabolic control in mice on HFD, suggesting that opaganib may be useful alone or in combination with existing therapies for weight management and improve conditions associated with obesity and diabetes.

Objective: Distinguishing diabetic nephropathy (DN) from non-diabetic renal disease (NDRD) remains challenging. This study developed and validated a machine learning model for differential diagnosis of DN and NDRD.

Methods: We included 100 type 2 diabetes mellitus (T2DM) patients with proteinuria from four Xuzhou hospitals (2013-2021), divided into DN (n=50) and NDRD (n=50) groups based on renal biopsy. Clinical data were used to build a predictive model. External validation was performed on 55 patients from The Affiliated Taian City Central Hospital of Qingdao University (2019-2023). Models were constructed using Python's scikit-learn library (v1.4.2), with feature selection via Recursive Feature Elimination (RFE).

Results: Compared to NDRD, DN patients had lower TG/Cys-c ratio [1.45 (0.75, 1.99) vs 2.78 (1.81, 4.48)], higher systolic blood pressure (156.80 ± 20.14 vs 137.66 ± 17.67), longer diabetes duration [78 (24, 120) vs 18 (6, 48) months], higher diabetic retinopathy prevalence (60% vs 40%), higher HbA1c [7.98 (6.50, 10.40) vs 7.10 (6.70, 7.90)], and lower hemoglobin (115.66 ± 22.20 vs 135.64 ± 18.59). The logistic regression (LR) model, incorporating TG/Cys-c ratio, SBP, diabetes duration, DR, HbA1c, and Hb, achieved an AUC of 0.9305, accuracy of 0.8333, sensitivity of 0.8283, and specificity of 0.8701. External validation showed an AUC of 0.9642, accuracy of 0.9455, sensitivity of 0.9615, and specificity of 0.9310. We named this method PDN (Prediction of Diabetic Nephropathy) and developed an online platform: http://cppdd.cn/service/PDN.

Conclusion: This machine learning-based method effectively differentiates DN from NDRD, aiding clinicians in diagnosis and treatment planning.

Background: Insulin-induced lipohypertrophy (LH) is a common complication of insulin therapy. However, its ultrasound characteristics, classification, and progression patterns remain poorly understood. This review aimed to systematically analyze the ultrasound characteristics and progression patterns of LH, and explore the relationship between different LH types and clinical outcomes.

Methods: A systematic literature search was conducted from January 2000 to October 2024 in PubMed, Web of Science, Embase, and Cochrane Library following PRISMA guidelines. Studies that examined LH using ultrasound in diabetic patients receiving insulin therapy were included. Two independent reviewers performed study selection and quality assessment using standardized tools.

Results: Twenty studies involving 5067 patients were included. Ultrasound showed significantly higher detection rates (57.6-100%) than physical examination (27.9-79.7%), with subclinical LH reported in 13.0-55% of cases. Twelve studies provided detailed ultrasound characteristics, with most describing well-defined borders, echo patterns predominantly showed hyper-echogenicity, and noted reduced or absent blood flow. Two ultrasound patterns were identified based on nodule size and echo patterns. Follow-up studies demonstrated distinct progression patterns and varying metabolic improvements among different LH types.

Conclusion: Ultrasound reveals three distinct patterns (nodular, diffuse, and hypoechoic), each with unique prognostic features, providing a basis for individualized management.

Background: The optimal composition of a hypocaloric diet for women with polycystic ovary syndrome (PCOS) remains uncertain. The aim of this study was to evaluate and compare the impacts of a hypocaloric high-protein diet (HPD) versus an isocaloric conventional calorie-restricted diet (CRD) with normal protein intake on the body composition and biochemical profiles of women diagnosed with PCOS combined with overweight or obesity.

Methods: This was a dietary intervention study evaluating the effects of two types of diets on women with PCOS who initiated weight loss independently at the Clinical Nutrition Clinic of Peking Union Medical College Hospital from March 2023 to March 2024 was carried out. Specifically, the records of 72 women with PCOS who were overweight or obese and underwent a 3-month weight management program were examined in a retrospective manner. The hypocaloric dietary intervention was adopted to achieve weight reduction, with either HPD or CRD. Body composition, serum lipids, glucose, insulin, and total testosterone (TT) were evaluated at baseline and post-intervention, and the differences were compared between and within groups.

Results: Both groups achieved significant weight loss, with the HPD group losing an average of -8.9 ± 4.6 kg and the CRD group losing -10.0 ± 9.4 kg, without a significant difference between them (P > 0.05). However, the HPD was superior in preserving fat-free mass (FFM) and fat-free mass index (FFMI), with losses of -1.5 ± 1.6 kg and -0.7 ± 1.1 kg/m², respectively, compared to the CRD group's losses of -4.4 ± 4.2 kg and -2.1 ± 1.9 kg/m² (P < 0.01). Additionally, the HPD group showed a more significant reduction in body fat percentage (-5.3 ± 3.3% vs -3.2 ± 4.5%, P < 0.05). Biochemical indicators were comparable in both groups.

Conclusion: Compared to an isocaloric standard-protein CRD, the dietary intervention with a HPD appears to be more helpful in preserving FFM in women with PCOS during a short-term weight loss program. Further well-designed trials are needed to verify our findings.

Purpose: The cardiovascular (CV) benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) are well established, but their effects on lower limb events (LLEs) remain inconclusive, with conflicting findings from clinical trials and real-world studies. This study aimed to assess the risks of CV and LLEs associated with SGLT2i compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with type 2 diabetes.

Patients and methods: The study included patients with type 2 diabetes who were newly prescribed SGLT2i or DPP-4i using data from the National Health Insurance Service in South Korea. A 1:1 propensity score matching method was used to assign 97,584 patients to the SGLT2i and DPP-4i groups. The study endpoints included all-cause mortality, CV events, and LLEs-a composite outcome encompassing diabetic foot or ulcer, amputation, debridement, graft transplantation or flap operation, and revascularization.

Results: Over a median follow-up of 2.74 years, the SGLT2i group had a lower incidence of all-cause mortality (hazard ratio [HR] 0.63, 95% CI 0.51-0.78), heart failure (HR 0.85, 95% CI 0.78-0.93), ischemic stroke (HR 0.77, 95% CI 0.67-0.88), and peripheral artery disease (HR 0.66, 95% CI 0.63-0.69) than the DPP-4i group. However, no significant difference was observed in the incidence of myocardial infarction (HR 1.06, 95% CI 0.87-1.28) or LLEs (HR 1.05, 95% CI 0.80-1.38) between the two groups.

Conclusion: In this nationwide, real-world study, SGLT2i use demonstrated a neutral effect on LLEs compared to DPP-4i in patients with type 2 diabetes. However, SGLT2i was associated with a lower risk of all-cause mortality, heart failure, ischemic stroke, and peripheral artery disease. These findings contribute to the ongoing debate on the safety of SGLT2i regarding LLEs and highlight their broader CV benefits, warranting further investigation into their long-term effects on lower limb complications.

Purpose: Yuquan capsule (YQC) is a well-known proprietary Chinese medicine used for the treatment of type 2 diabetes mellitus. The aim of this study was to investigate the potential mechanism and efficacy of YQC in the treatment of T2DM by means of metabolomics.

Methods: Thirty-two male SD rats were randomly divided into four groups of control, type 2 diabetic mellitus (T2DM), metformin (Met), and YQC. Establishment of the T2DM model by high-fat diet (HFD) and streptozotocin (STZ). Fasting blood glucose (FBG) and weight were measured weekly, urine output was collected and recorded. The blood, kidney, pancreas, and liver tissue samples were collected at the end of the experiment. Blood samples were analyzed with methods of ELISA, pancreas, and liver tissues were analyzed by pathological sections, and serum was analyzed by metabolomics using ultra-performance liquid chromatography quadrupole time-of-flight coupled with mass spectrometry (UPLC-Q/TOF-MS).

Results: It was observed that YQC could reduce blood glucose levels by modulating blood lipid and transaminase indices, and by diminishing the concentration of inflammatory factors within hepatic and pancreatic tissues. Furthermore, YQC restores homeostasis by regulating lipid and amino acid metabolism, engaging 21 biomarkers and 10 metabolic pathways.

Conclusion: YQC has the capacity to enhance blood lipid and transaminase levels, suppress the expression of inflammatory factors, and foster the homeostatic progression of metabolic circulation in rats with T2DM.