Comparison of ß-Cell Function and Insulin Sensitivity Between Normal-Weight and Obese Chinese With Young-Onset Type 2 Diabetes.

Normal-weight individuals with usual-onset type 2 diabetes have reduced ß-cell function and greater insulin sensitivity compared with their obese counterparts. The relative contribution of ß-cell dysfunction and insulin resistance to young-onset type 2 diabetes (YOD) among normal-weight individuals is not well established. In 44 individuals with YOD (24 with normal weight and 20 with obesity) and 24 healthy control individuals with normoglycemia (12 with normal weight and 12 with obesity), we conducted 2-h 12 mmol/L hyperglycemic clamps to measure acute (0-10 min) and steady-state (100-120 min) insulin and C-peptide responses, as well as insulin sensitivity index. Normal-weight individuals with YOD had lower acute insulin response, steady-state insulin and C-peptide responses, and a higher insulin sensitivity index compared with their obese counterparts with YOD. Compared with BMI-matched healthy control individuals, normal-weight individuals with YOD had lower acute and steady-state insulin and C-peptide responses but a similar insulin sensitivity index. The impairment of steady-state ß-cell response relative to healthy control individuals was more pronounced in normal-weight versus obese individuals with YOD. In conclusion, normal-weight Chinese with YOD exhibited worse ß-cell function but preserved insulin sensitivity relative to obese individuals with YOD and BMI-matched healthy individuals with normoglycemia. The selection of glucose-lowering therapy should account for pathophysiological differences underlying YOD between normal-weight and obese individuals.

Dysregulation of iron transport-related biomarkers in blood leukocytes is associated with poor prognosis of early trauma.

Objective: The early targeted and effective diagnosis and treatment of severe trauma are crucial for patients' outcomes. Blood leukocytes act as significant effectors during the initial inflammation and activation of innate immunity in trauma. This study aims to identify hub genes related to patients' prognosis in blood leukocytes at the early stages of trauma. Methods: The expression profiles of Gene Expression Omnibus (GEO) Series (GSE) 36809 and GSE11375 were downloaded from the GEO database. R software, GraphPad Prism 9.3.1 software, STRING database, and Cytoscape software were used to process the data and identify hub genes in blood leukocytes of early trauma. Results: Gene Ontology (GO) analysis showed that the differentially expressed genes (DEGs) of blood leukocytes at the early stages of trauma (0-4 h, 4-8 h, and 8-12 h) were mainly involved in neutrophil activation and neutrophil degranulation, neutrophil activation involved in immune response, neutrophil mediated immunity, lymphocyte differentiation, and cell killing. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were mainly involved in Osteoclast differentiation and Hematopoietic cell lineage. Sixty-six down-regulated DEGs and 148 up-regulated DEGs were identified and 37 hub genes were confirmed by Molecular Complex Detection (MCODE) of Cytoscape. Among the hub genes, Lipocalin 2 (LCN2), Lactotransferrin (LTF), Olfactomedin 4 (OLFM4), Resistin (RETN), and Transcobalamin 1 (TCN1) were related to prognosis and connected with iron transport closely. LCN2 and LTF were involved in iron transport and had a moderate predictive value for the poor prognosis of trauma patients, and the AUC of LCN2 and LTF was 0.7777 and 0.7843, respectively. Conclusion: As iron transport-related hub genes in blood leukocytes, LCN2 and LTF can be used for prognostic prediction of early trauma.

Comparison of beta-cell function between Hong Kong Chinese with young-onset type 2 diabetes and late-onset type 2 diabetes.

AIMS: We compared beta-cell function in Chinese with type 2 diabetes diagnosed at age < 40 years (young-onset diabetes, YOD) and ≥ 40 years (late-onset diabetes, LOD). METHODS: In this cross-sectional study, we selected participants from two cohorts of people with type 2 diabetes recruited in 1996-2012 (n = 4,376) and 2020-2021 (n = 794). Multivariable linear regression models were applied to compare homeostasis model assessment of beta-cell function (HOMA2-%B) and fasting plasma C-peptide across diabetes duration at enrolment between YOD and LOD. RESULTS: The YOD group (n = 1,876, mean [SD] age: 39.9 [7.5] years, median [IQR] diabetes duration: 6 [2-12] years) was more likely to have family history of diabetes (61.6 % vs 43.6 %), obesity (41.9 % vs 26.8 %), dyslipidaemia (61.7 % vs 54.4 %), and worse glycaemic control (mean HbA1c 7.7 % vs 7.4 %) than those with LOD (n = 3,294, age: 60.8 [10.6] years, diabetes duration: 5 [1-10] years). When compared to people with LOD, HOMA2-%B and fasting plasma C-peptide were lower in the YOD group, consistently among those with BMI < 27.5 kg/m2 and HOMA2-IR ≤ 1.6 (median value), adjusted for year at enrolment, sex, diabetes duration, family history of diabetes, HbA1c, weight and lipid indices (p < 0.01). Cross-sectionally, the slopes of decline in HOMA2-%B by diabetes duration were greater in YOD than LOD among individuals with BMI < 27.5 kg/m2 (p-interaction = 0.015). CONCLUSIONS: Chinese with YOD had accelerated loss of beta-cell function than those with LOD especially in non-obese individuals.

Incident cardiovascular-kidney disease, diabetic ketoacidosis, hypoglycaemia and mortality in adult-onset type 1 diabetes: a population-based retrospective cohort study in Hong Kong.

Background: Type 1 diabetes can occur at any age. The majority of literature on type 1 diabetes were reported in children whereas adult-onset type 1 diabetes is less well characterised. This study aims to compare the risk of diabetes-related complications and mortality in Chinese with adult-onset type 1 diabetes versus those with youth-onset type 1 diabetes and adult-onset type 2 diabetes. Methods: Between 2000 and 2018, 2738 people with type 1 and 499,288 with type 2 diabetes underwent metabolic and complication assessment in Hong Kong Hospital Authority. They were followed for incident diabetic ketoacidosis (DKA), severe hypoglycaemia, end-stage kidney disease (ESKD), cardiovascular disease (CVD) and all-cause mortality until 2019. Findings: In multivariable Cox regression adjusted for sex, diabetes duration and calendar year, people with type 1 diabetes diagnosed aged ≥40 years had a lower hazard of DKA (hazard ratio HR [95% CI] 0.47 [0.32-0.70]) but higher hazards of severe hypoglycaemia (HR 1.37 [1.13-1.67]), ESKD (HR 4.62 [2.90-7.37]), CVD (HR 11.44 [6.92-18.91]) and mortality (HR 16.22 [11.43-23.02]) versus those diagnosed aged <20 years. Compared with peers with type 2 diabetes presenting at comparable age, people with type 1 diabetes diagnosed aged ≥40 years had higher age-, sex- and diabetes duration-adjusted hazards of DKA (HR 19.87 [13.95-28.31]), severe hypoglycaemia (HR 3.26 [2.81-3.80]), ESKD (HR 1.58 [1.20-2.09]) and mortality (HR 2.26 [1.96-2.60]), and a similar hazard of CVD (HR 1.11 [0.87-1.43]). These associations remained constant after adjustment for metabolic indices. Interpretation: People with type 1 diabetes diagnosed in late adulthood had elevated risks of a broad range of complications and mortality compared with people with youth-onset type 1 diabetes and people with type 2 diabetes presenting at same age bands. Funding: This study did not receive any specific funding.

Higher incidence of cardiovascular-kidney complications in Chinese with youth-onset type 2 diabetes versus youth-onset type 1 diabetes attenuated by control of cardio-metabolic risk factors: A population-based prospective cohort study in Hong Kong.

AIMS: To determine and compare the incidence of diabetes complications in Chinese with youth-onset type 2 and type 1 diabetes. METHODS: We conducted a population-based prospective cohort study, including 1,260 people with type 2 diabetes and 1,227 with type 1 diabetes diagnosed at age < 20 years who underwent metabolic and complication assessment in Hong Kong Hospital Authority between 2000 and 2018. They were followed for incident cardiovascular disease (CVD), end-stage kidney disease (ESKD) and all-cause death until 2019. Multivariable Cox regression analysis was applied to compare the risks of these complications in type 2 versus type 1 diabetes. RESULTS: People with type 1 diabetes (median age: 20 years, median diabetes duration: 9 years) and type 2 diabetes (median age: 21 years, median diabetes duration: 6 years) were followed for a mean period of 9.2 and 8.8 years respectively. The risks of CVD (HR [95 % CI] 1.66 [1.01-2.72]) and ESKD (HR 1.96 [1.27-3.04]) but not death (HR 1.10 [0.72-1.67]) were higher in type 2 versus type 1 diabetes, adjusted for age at diagnosis, diabetes duration and sex. The association became nonsignificant with further adjustment for glycaemic and metabolic control. Youth-onset type 2 diabetes conferred mortality excess (standardized mortality ratio 4.15 [3.28-5.17]) to age- and sex-matched general population. CONCLUSIONS: People with youth-onset type 2 diabetes had higher incidence rates of CVD and ESKD than type 1 diabetes. The excess risks in type 2 diabetes were removed after adjusted for cardio-metabolic risk factors.

HIF-1α promotes the expression of syndecan-1 and inhibits the NLRP3 inflammasome pathway in vascular endothelial cells under hemorrhagic shock.

Hemorrhagic shock (HS) is a global life-threatening matter that causes massive mortality annually worldwide. Syndecan-1 (SDC1) is an important predictor and evaluation index for HS, but its mechanism involved in the HS development remain unclear. HS mice model and human umbilical vein endothelial cells (HUVECs) under hypoxia were applied to explore the relationship of SDC1 with HIF-1α and NLRP3 inflammasome in vascular ECs under HS. Transcriptome sequencing of isolated vascular ECs were conduct to search for hub genes. Dual luciferase assay was adopted to prove the binding effects of the HIF-1α on SDC1 promoter in HUVECs. Molecular expression was evaluated through routine experiments. Here, HS led to aggravated lung injury and inflammatory response with the shedding of SDC1 on the lung vascular ECs in mice. Circulatory SDC1 and proinflammatory cytokines were significantly increased after HS. HIF-1α and IL-1ß were identified as hub genes in vascular ECs of HS mice. Meanwhile, HIF-1α-mediaed hypoxia and IL-1ß-involved NLRP3 inflammasome pathways were activated following HS. The transcriptional factor HIF-1α promoted the expression of SDC1 through binding to the SDC1 promoter. SDC1 had an inhibitory effect on the NLRP3 inflammasome activity. An exogenous increase of HIF-1α upregulated SDC1 and restrained the activation of the NLRP3 inflammasome under hypoxia, while further interference of SDC1 weakened this effect. Hence, SDC1 is an intermediate connecting HIF-1α and NLRP3 inflammasome in the vascular ECs under hypoxia. HIF-1α promotes the expression of SDC1 and inhibits the NLRP3 inflammasome pathway in vascular ECs under HS.

Incidence of long-term diabetes complications and mortality in youth-onset type 2 diabetes: A systematic review.

AIMS: This systematic review aims to assess the incidence of chronic kidney disease (CKD), cardiovascular disease (CVD) and mortality in people with type 2 diabetes diagnosed <20 years. METHODS: We searched MEDLINE, Embase and Cochrane Library for longitudinal studies published between 1 January 2000 and 31 November 2021. RESULTS: Seventeen studies (15 reporting CKD, 3 reporting CVD, 5 reporting mortality) from seven countries of sample size ranging between 96 and 4,141 were eligible. Most studies were conducted in North America and Europe (n = 14). Diabetes duration at enrolment varied from 0 to 8.3 years and follow-up duration from 1 to 12.6 years. The incidence rates (per 1,000 person-year) of albuminuria ranged between 12.4 and 114.8, macroalbuminuria or proteinuria between 10 and 35.0, end-stage kidney disease (ESKD) between 0.4 and 25.0, CVD between 3.7 and 19.5, and mortality between 1.0 and 18.6. The highest incidence rates of albuminuria, ESKD and mortality were recorded in Australian Aboriginal and Pima Indian populations. Youth-onset type 2 diabetes was associated with greater risk of developing CKD compared with type 1 diabetes in most studies. CONCLUSION: Studies reporting CVD in youth-onset type 2 diabetes are scarce. Estimated incidence rates of CKD and mortality in youth-onset type 2 diabetes varied across different study populations, potentially higher in indigenous people. Youth with type 2 diabetes are at higher risk of adverse kidney outcomes than their type 1 counterparts. More studies are needed in regions outside of North America and Europe.

Plasma D-dimer as a predictor of intraluminal thrombus burden and progression of abdominal aortic aneurysm.

AIM: Intraluminal thrombus (ILT) is presented in most abdominal aortic aneurysms (AAAs) and is suggested to promote AAA expansion. D-dimer, a breakdown product in the thrombus remodeling, may have prognostic value for AAA. This study investigated the interrelation between plasma D-dimer level, ILT volume, AAA size and progression. MAIN METHODS: This was a retrospective observational study that involved 181 patients with infra-renal AAA. They were divided into small and large AAA groups according to AAA diameter. 24 of them had repeated abdominal computed tomography angiography (CTA) scan and were divided into slow-growing and fast-growing AAA groups according to the median value of AAA growth rate. Baseline and follow-up plasma D-dimer level, maximum diameter of AAA, total infra-renal aortic volume and ILT volume were analyzed. KEY FINDINGS: Plasma D-dimer level was positively correlated with ILT volume (R = 0.382, P < 0.001) and maximum diameter of AAA (R = 0.442, P < 0.001). Increasing value of plasma D-dimer was positively associated with the accelerated growth rate of AAA (R = 0.720, P < 0.01). ILT volume showed positive correlation with maximum diameter (R = 0.859, P < 0.001) and growth rate of AAA (R = 0.490, P < 0.05). After adjusting the baseline ILT volume, the positive correlations remained to be statistically significant between plasma D-dimer level and AAA size (R = 0.200, P < 0.05), as well as increasing value of plasma D-dimer and growth rate of AAA (R = 0.642, P < 0.05). SIGNIFICANCE: Plasma D-dimer level reflected ILT burden in AAAs. Plasma D-dimer level and ILT volume were positively correlated with AAA size. Increasing value of plasma D-dimer and baseline ILT volume could be predictors of AAA progression.

Ulinastatin and/or thymosin α1 for severe sepsis: A systematic review and meta-analysis.

OBJECTIVE: Ulinastatin (UTI) and thymosin α1 (Tα1) have been investigated for their immunoregulatory properties in patients with severe sepsis. However, it is unclear whether immunomodulatory therapy using UTI combined with Tα1 (UCT), UTI alone (UA), or Tα1 alone (TA) improves the disease outcome. The objective of this study was to analyze the effectiveness of UCT, UA, and TA for the treatment of severe sepsis. METHODS: PubMed, EMBASE, and Cochrane Library databases were investigated from inception to September 2015. Randomized controlled trials (RCTs) examining the treatment of patients with severe sepsis by UCT, UA, and TA were defined as eligible. Data were analyzed using Review Manager 5.3, and the RCTs were evaluated by the Cochrane Handbook 5.1.0. The quality of the evidence was evaluated according to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). RESULTS: Ten articles and 12 studies were included in this systematic review and meta-analysis. The primary outcome measures indicated that UCT was associated with significantly lower 28-day mortality (risk ratio [RR], 0.67; 95% confidence interval [CI], 0.57-0.80; p < 0.00001; n = 915; GRADE rating, moderate) and 90-day mortality (RR, 0.75; 95% CI, 0.61-0.93; p = 0.009; n = 547; GRADE rating, moderate); UA was associated with no significant difference in the 28-day mortality (RR, 0.60; 95% CI, 0.30-1.20; p = 0.15; n = 182; GRADE rating, low), and there was no report on 90-day mortality; TA was associated with significantly lower 28-day mortality (RR, 0.72; 95% CI, 0.55-0.93; p = 0.01; n = 494; GRADE rating, low), but there was no significant difference in the 90-day mortality (RR, 0.84; 95% CI, 0.54-1.31; p = 0.45; n = 91; GRADE rating, very low). In the secondary outcome measures, there was obvious heterogeneity in the length of the intensive care unit stay and that of the mechanical ventilation, length of the antibiotics and vasopressor use, and 28-day Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. CONCLUSION: Treatment of severe sepsis with UCT reduced both the 28-day and the 90-day mortality, whereas treatment with TA reduced only the 28-day mortality. The effects of UCT, UA, and TA on intensive care unit stay, mechanical ventilation, antibiotics and vasopressor use, and 28-day APACHE II scores of septic patients are still unclear. Additional high-quality RCTs are needed to define clearly the guidelines for the treatment of severe sepsis. LEVEL OF EVIDENCE: Systematic review, level IV.

A comparison of measurement methods and sexual dimorphism for digit ratio (2D:4D) in Han ethnicity.

The digit ratio (2D:4D) is sexually dimorphic and has been considered an indicator of prenatal sex hormone exposure. Previous studies have shown that males tend to have lower 2D to 4D ratio than females, and this sexual dimorphism has been reported across different ethnic groups and different countries. However, digit ratio data are missing from the Han ethnicity in China. Furthermore, most of the previous studies used direct measurement for digit ratio. In this article, we used multiple measurement methods, including the direct measurement and two X-ray measurement methods to examine the trait of 2D:4D in Chinese Han. Our sample consisted of 128 men and 122 women from Liaoning Medical University. They were 18-20 years old. The direct measurement and two types of X-ray measurements of the length of their 2nd and 4th fingers were used separately to calculate digit ratios. Soft tissue thickness of 2D and 4D fingertips were also assessed from the two X-ray methods. The results suggest that (1) sex differences in 2D:4D tend to be stronger in the two X-ray measurements in comparison to the direct measurement; (2) 2D:4D ratios from X-ray measurements tend to be lower than that from the direct measurement; (3) Han ethnicity have a lower mean value of 2D:4D than other ethnic groups; (4) no sex difference in the soft tissue of finger tips. In conclusion, the digit ratio is lower in both men and women in Han, and the sexual dimorphism in digit ratio was stronger with X-ray measurements in comparison to the direct measurement.