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

Hyperinsulinemic Hypoglycemia (HH) is a rare condition that affects newborn children in the postnatal period, represented by dangerously low levels of blood glucose in a persistent manner, which puts the baby at high risk of multiple issues, especially regarding the brain cells if the baby does not take the appropriate medication or have the correct diagnosis. Hyperinsulinemic Hypoglycemia can happen due to an active or inactive mutation in 16 genes responsible for glucose metabolism and insulin secretion (GLUD1, GCK, SLC16A1, HK1, CACNA1D, KCNJ11, ABCC8, FOXA2, HNF1A, HNF4A, HADH, PGM1, UCP2, KCNQ1, PMM2, EIF2S3). These mutations can take place in many forms, either defused or local, affecting several or all pancreatic beta cells respectively. This review summarizes genetic variations diagnosis and treatment of Hyperinsulinemic Hypoglycemia.

Purpose: To explore the correlation between fasting C-peptide to diabetes duration ratio (FCP/DD) and diabetic peripheral neuropathy (DPN).

Methods: The study was conducted on 816 patients with type 2 diabetes (T2DM). Subjects were classified into a diabetic peripheral neuropathy group (DPN, n=408) and a non-diabetic peripheral neuropathy group (NDPN, n=408) depending on the presence of DPN. Collected patients' baseline data, calculated the FCP/DD ratio, and analyzed the correlation between FCP/DD and DPN.

Results: A comparative analysis of general characteristics revealed that the DPN group exhibited higher values for age, DD, proportion of hypertension, proportion of DN, and proportion of DR compared to the NDPN group, Conversely, the DPN group demonstrated lower proportions of eGFR, FCP/DD, FCP, and fatty liver relative to the NDPN group, with all differences achieving statistical significance (P < 0.05). Compared to the high FCP/DD group, the low FCP/DD group exhibited higher values in age, DD, the proportion of DPN, DN, DR, and hypertension, as well as elevated levels of HDL-C and NEUT (P<0.05). Conversely, the low FCP/DD group demonstrated a lower proportion of patients who smoked and those with fatty liver, along with reduced BMI, ALB, FBG, UA, eGFR, TC, TG, and LDL-C levels (P < 0.05). In patients with T2DM, after adjusting for confounding factors, high levels of FCP/DD were found to be a protective factor for DPN (P < 0.05). The area under the curve of the FCP/DD Model predicting DPN (AUC=0.737) was higher than that of single FCP (AUC=0.587), DD (AUC=0.665).

Conclusion: The high FCP/DD ratio was a protective factor for T2DM with DPN. Additionally, the FCP/DD ratio was found to be a better predictor for the occurrence of DPN in T2DM compared to FCP and DD alone.

Background: Functional defects caused by mutations in the insulin receptor (INSR) gene often lead to severe hereditary insulin resistance syndromes, including but not limited to type A insulin resistance syndrome.

Method and result: Here, we report a case of a 12-year-old girl with elevated fasting blood glucose detected by opportunistic testing, associated with severe insulin resistance and hyperandrogenemia. She had axillary hair, acne, clitoral hypertrophy, prominent labia minora hypertrophy and thickened voice with BMI 20.57kg/m², and ultrasound imaging showed that she had multiple follicles in both ovaries. Insulin was initially administered, but the glycemic control was poor. Accordingly, the prescription was later switched to metformin, maintaining euglycemic blood glucose level. The whole exome sequencing from peripheral blood revealed that the patient carries NM_000208.2:c.1225_1227delTTC (p.Phe409del) heterozygous mutation in the INSR gene. She was tentatively diagnosed as type A insulin resistance syndrome based on her clinical features and heterozygous mutation in the INSR gene.

Conclusion: Our results demonstrated that type A insulin resistance syndrome in patients presenting with severe insulin resistance and hyperandrogenemia was associated with a heterozygous variant of c.1225_1227delTTC (p.Phe409del), suggesting that exon sequencing would be beneficial to detect the potential mutations in the INSR gene of these patients for precise diagnosis and intervention in clinical practice.

Objective: This study aimed to systematically review the existing research on risk prediction models for mild cognitive impairment in patients with type 2 diabetes mellitus and to analyze the predictive performance of these models.

Methods: A systematic computerized search was conducted for studies published in CNKI, Wanfang, VIP, CBM, PubMed, Embase, Cochrane Library, CINAHL, and Web of Science regarding risk prediction models for mild cognitive impairment in patients with type 2 diabetes mellitus, covering the period the inception of the databases through November 10, 2024. Two independent reviewers performed literature screening and data extraction based on predefined inclusion and exclusion criteria. The risk of bias and the applicability of the included studies were subsequently evaluated using the Risk of Bias Assessment Tool for Prediction Models. A meta-analysis of the predictive performance of the models was performed using Stata 17.0 software.

Results: A total of 12 studies and 17 prediction models were included in the analysis, with the area under the receiver operating characteristic curve (AUC) for the models ranging from 0.743 to 0.987. All studies were assessed to be at high risk of bias, particularly concerning the issue of underreporting in the area of data analysis. The combined AUC value of the six validated models was 0.854, indicating that these models exhibited favorable predictive performance. The multivariate models consistently identified age, education, disease duration, depression, and glycosylated hemoglobin level as independent predictors.

Conclusion: The development of risk prediction models for mild cognitive impairment in patients with type 2 diabetes mellitus is still in its infancy. In order to develop more accurate and practical risk prediction models for mild cognitive impairment in patients with type 2 diabetes mellitus, future studies must rely on large-sample, multicenter prospective cohorts and adhere to rigorous study designs.

Objective: Lipohypertrophy (LH) is a localized complication of type 2 diabetes mellitus in patients on long-term insulin therapy. Sound touch elastography (STE) is a crucial tool in the quantitative real-time assessment of tissue hardness within specific target regions. This study aims to explore the efficacy of STE in evaluating the hardness of subcutaneous LH at insulin injection sites in individuals with type 2 diabetes mellitus and investigate the correlations between the hardness of LH lesions and various clinical indicators.

Methods: A cohort of 53 individuals with type 2 diabetes mellitus undergoing insulin therapy at the Department of Endocrinology, Affiliated People's Hospital of Ningbo University from April 2023 to January 2024 was selected. General clinical data of the participants and STE-derived Young's modulus hardness values of the LH lesions and adjacent normal adipose tissue were collected. The Wilcoxon signed-rank test was employed for comparative analysis between the two tissue groups, while Spearman's rank correlation was used to examine the relationships between Young's modulus values of the LH lesions and clinical indicators.

Results: Routine ultrasound examination revealed LH in all 53 participants. The maximum (E_max), average (E_mean), and minimum (E_min) values of Young's modulus significantly differed between the LH lesions and surrounding healthy adipose tissue (Z=-6.334, P<0.001; Z=-6.263, P<0.001; Z=-5.865, P<0.001, respectively), indicating greater hardness in the LH lesions. Additionally, the E_min values of the LH lesions were positively correlated with the glycated hemoglobin levels (r=0.293, P<0.05).

Conclusion: Ultrasound elastography-based STE exhibits great potential in assessing LH hardness in individuals undergoing insulin therapy for type 2 diabetes mellitus. STE offers a novel and objective ultrasonographic approach for accurately evaluating LH severity, highlighting the significance of this technique in clinical diagnostics.

Purpose: Our objective is to investigate the potential involvement of free triiodothyronine (FT3), a key bioactive compound found in thyroid hormones (THs) in the pathogenesis of diabetic peripheral neuropathy (DPN) in patients diagnosed with type 2 diabetes mellitus (T2DM).

Patients and methods: A total of 121 T2DM patients were recruited. And then, they were divided into the control group and the DPN group. Clinical parameters were collected for each patient. Additionally, nerve conduction velocity was tested using neurophysiological methods. Correlation and regression analyses were employed to examine the relationship between the concentrations of FT3 and DPN.

Results: Compared to 57 patients without DPN, 64 patients with DPN showed increased HbA1c and low-density lipoprotein cholesterol (LDL-C) levels (P=0.001 and 0.042), as well as decreased concentrations of FT3 (P=0.042). Additionally, FT3 levels are positively associated with the motor and sensory fibers conduction velocity of the Ulnar nerve, as well as the motor conduction velocity of the Tibial nerve, with (R=0.205, P=0.025; R=0.191, P=0.038; R=0.220, p=0.016) or without (R=0.257, P=0.004; R=0.227, P=0.012; R=0.227, p=0.012) adjustment for HbA1c and LDL-C. Furthermore, multiple linear regression analysis suggests that decreased FT3 levels may influence the motor and sensory fibers conduction velocity of the Ulnar nerve (β=0.795, P=0.025 and β=0.909, P=0.038), as well as the motor conduction velocity of the Tibial nerve (β=0.727, P=0.016). Moreover, our study demonstrated that decreased FT3 levels are one of the risk factors for DPN in T2DM patients, as determined by binary logistic regression analysis (OR=0.542, P=0.022).

Conclusion: Lower concentrations of FT3 are one of the risk factors for DPN in patients with T2DM. Additionally, decreased FT3 levels may influence peripheral neuropathy, particularly affecting the motor and sensory fibers conduction velocity of the ulnar nerve, as well as the motor fiber conduction velocity of the tibial nerve.

Purpose: This study aimed to investigate the risk factors and predictors of non-obese fatty liver disease in the Chinese population.

Patients and methods: A total of 6,014 adults who underwent physical examinations at Union Hospital of Huazhong University of Science and Technology from March 2019 to March 2023 were included in this study. Fatty liver disease was diagnosed based on at least two of the following criteria: diffuse echo patterns relative to the liver, spleen, and kidney; ultrasonic beam attenuation; and poor intrahepatic visual details. The associations between non-obese fatty liver and gender, age, total bilirubin(TBIL), direct bilirubin(DBIL), alanine aminotransferase(ALT), aspartate aminotransferase(AST), glutamine transferase(GGT), alkaline phosphatase(ALP), triglycerides(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDLC), low-density lipoprotein cholesterol(LDLC), urea nitrogen(BUN), creatinine(Cr), uric acid(UA), Central nervous system sensitivity PTFQI, TSHI, TT4RI, TFQI, Peripheral sensitivity, free thyroxine(FT₄), thyroid-stimulating hormone(TSH), triiodothyronine(FT₃), fasting blood glucose(FBG), systolic blood pressure(SBP), diastolic blood pressure(DBP), body mass index(BMI) were analyzed via binary logistic regression. Correlation between non-obese fatty liver and high blood lipids, hypertension, hyperuricemia, diabetes, thyroid dysfunction were analyzed using the Pearson and Spearman methods. ROC curve was used to evaluate the diagnostic effect of the indicator.

Results: Compared with the normal group, age, proportion of males, ALT, AST, GGT, ALP, TG, TC, BUN, Cr, UA, TSHI, TT4RI, FT₃/FT₄, TSH, FT₃, FBG, SBP, DBP and BMI in the disease group were significantly higher. The prevalence of non-obese fatty liver was associated with hyperlipidemia, hypertension, hyperuricemia and diabetes. Gender, age, DBIL, ALT, ALP, TG, HDL-C, LDL-C, BUN, UA, FBG, DBP, BMI were independent risk factors for non-obese fatty liver.FT₃/FT₄ may be considered as a predictor of nonobese fatty liver.

Conclusion: Risk factors for non-obese fatty liver may include sex, age, TG, TC, BMI, etc. Hyperlipidemia, hypertension, hyperuricemia and diabetes mellitus are related to non-obese fatty liver. FT₃/FT₄ may be a predictor of non-obese fatty liver disease.

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Objective: To investigate the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular outcomes in patients with acute coronary syndrome (ACS) and type 2 diabetes (T2D).

Methods: The clinical data of 88 patients with ACS and T2D who were treated with SGLT2i between January 2020 and December 2021 were collected as the case group through convenience sampling. Patients taking other hypoglycaemic drugs were included as the control group in a 1:1 ratio matched with the case group using retrospective propensity score matching. Relevant data were subsequently collected from both groups for comparison.

Results: Statistically significant differences were observed in glycated haemoglobin (HbA1c) between the two groups (8.11[6.93, 9.41] vs 7.51[6.52, 9.14]%; Z=2.109; P=0.035). The SGLT2i group showed a decrease in major adverse cardiovascular events (MACEs) (P<0.001), secondary composite endpoint events (P=0.024), heart failure readmission (P=0.042) and unplanned revascularisation (P=0.014) compared with the control group. Moreover, the multivariate analysis showed that SGLT2i significantly reduced the risk of MACEs (hazard ratio [HR], 0.472; 95% CI, 0.321-0.694; P<0.001) and unplanned revascularisation (HR, 0.422; 95% CI, 0.212-0.842; P=0.014). In patients with reduced ejection fraction, SGLT2i significantly reduced the risk of MACEs (HR, 0.258; 95% CI, 0.106-0.626; P=0.003) compared with the control group. By contrast, in patients without reduced ejection fraction, SGLT2i significantly reduced the risk of MACEs (HR, 0.640; 95% CI, 0.412-0.996; P=0.048) and unplanned revascularisation (HR, 0.464; 95% CI, 0.222-0.969; P=0.041) compared with the control group.

Conclusion: In addition to significantly reducing the risk of adverse cardiovascular events and unplanned revascularisation in patients with ACS and T2D, the use of SGLT2i can reduce the risk of adverse cardiovascular events regardless of the presence of reduced ejection fraction.

Purpose: The axon guidance factors and Rho/ROCK pathway play crucial roles in axon protection and nerve repair and has been implicated in the development of diabetic peripheral neuropathy (DPN). This study investigates the protective effects of quercetin against DPN, focusing on axon guidance factors and Rho/ROCK pathway.

Methods: DPN was induced by intraperitoneal injection of streptozotocin (STZ) to Sprague-Dawley rats. The DPN model rats were allocated into three groups and administered quercetin at two different doses (30 mg/kg/day and 60 mg/kg/day) or a placebo. Concurrently, healthy rats were divided into two groups and administered either a placebo or quercetin (60 mg/kg/day). Administration was initiated 8 weeks post-STZ injection and continued for a duration of six weeks. To assess quercetin's neuroprotective effects, biochemical analyses, neurological function tests (mechanical threshold, thermal response latency, motor nerve conduction velocity), and morphological assessments via transmission electron microscopy were conducted. Immunofluorescence and immunohistochemical assays were performed on sciatic nerve tissue and high glucose-induced RSC96 rat Schwann cells to explore quercetin's pharmacological effects on DPN.

Results: Quercetin exhibited neuroprotective effects on both DPN rats and RSC96 cells exposed to high-glucose. A six-week administration of quercetin at both doses significantly improved the peripheral neurological functions and alleviated the pathological changes in sciatic nerve of DPN rats (P<0.05). Mechanistically, quercetin markedly upregulated the expressions of axonal growth factors, Slit-2 and Netrin-1 in vivo and in vitro (P<0.05), while inhibiting the aberrant activation of Rho/ROCK signaling pathway in the sciatic nerve of DPN rats.

Conclusion: Our findings suggest that quercetin improves DPN through a novel mechanism, indicating its potential as a therapeutic agent for DPN therapy.