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Cardiovascular Diabetology Jun 2024The atherogenic index of plasma (AIP) is closely associated with the onset of diabetes, with obesity being a significant risk factor for type 2 diabetes mellitus (T2DM)....
BACKGROUND
The atherogenic index of plasma (AIP) is closely associated with the onset of diabetes, with obesity being a significant risk factor for type 2 diabetes mellitus (T2DM). However, the association between the AIP and T2DM in overweight and obese populations has been infrequently studied. Therefore, this study aimed to explore this association in overweight and obese individuals with T2DM.
METHODS
This cross-sectional analysis utilized data from 40,633 participants with a body mass index (BMI) ≥ 24 kg/m who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were categorized into groups of overweight and obese individuals with and without diabetes according to the T2DM criteria. The AIP, our dependent variable, was calculated using the formula log10 [(TG mol/L)/HDL-C (mol/L)]. We investigated the association between the AIP and T2DM in overweight and obese individuals using multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and threshold effect analysis. Additionally, mediation analysis evaluated the role of inflammatory cells in AIP-related T2DM.
RESULTS
Overweight and obese patients with T2DM exhibited higher AIP levels than those without diabetes. After adjusting for confounders, our results indicated a significant association between the AIP and the risk of T2DM in overweight and obese individuals (odds ratio (OR) = 5.17, 95% confidence interval (CI) 4.69-5.69). Notably, participants with a high baseline AIP (Q4 group) had a significantly greater risk of T2DM than those in the Q1 group, with an OR of 3.18 (95% CI 2.94-3.45). Subgroup analysis revealed that the association between the AIP and T2DM decreased with increasing age (interaction P < 0.001). In overweight and obese populations, the association between AIP and T2DM risk displayed a J-shaped nonlinear pattern, with AIP > - 0.07 indicating a significant increase in T2DM risk. Various inflammatory cells, including neutrophils, leukocytes, and monocytes, mediated 4.66%, 4.16%, and 1.93% of the associations, respectively.
CONCLUSION
In overweight and obese individuals, the AIP was independently associated with T2DM, exhibiting a nonlinear association. Additionally, the association between the AIP and T2DM decreased with advancing age. Multiple types of inflammatory cells mediate this association.
Topics: Humans; Diabetes Mellitus, Type 2; Middle Aged; Male; Female; Cross-Sectional Studies; Obesity; Risk Factors; China; Risk Assessment; Biomarkers; Adult; Aged; Body Mass Index; Atherosclerosis; Triglycerides; Overweight; Cholesterol, HDL; Prognosis; East Asian People
PubMed: 38951808
DOI: 10.1186/s12933-024-02330-y -
Cardiovascular Diabetology Jun 2024Glucokinase (GK) plays a key role in glucose metabolism. In the liver, GK is regulated by GK regulatory protein (GKRP) with nuclear sequestration at low plasma glucose...
BACKGROUND
Glucokinase (GK) plays a key role in glucose metabolism. In the liver, GK is regulated by GK regulatory protein (GKRP) with nuclear sequestration at low plasma glucose level. Some GK activators (GKAs) disrupt GK-GKRP interaction which increases hepatic cytoplasmic GK level. Excess hepatic GK activity may exceed the capacity of glycogen synthesis with excess triglyceride formation. It remains uncertain whether hypertriglyceridemia associated with some GKAs in previous clinical trials was due to direct GK activation or impaired GK-GKRP interaction.
METHODS
Using publicly available genome-wide association study summary statistics, we selected independent genetic variants of GCKR and GCK associated with fasting plasma glucose (FPG) as instrumental variables, to mimic the effects of impaired GK-GKRP interaction and direct GK activation, respectively. We applied two-sample Mendelian Randomization (MR) framework to assess their causal associations with lipid-related traits, risks of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular diseases. We verified these findings in one-sample MR analysis using individual-level statistics from the Hong Kong Diabetes Register (HKDR).
RESULTS
Genetically-proxied impaired GK-GKRP interaction increased plasma triglycerides, low-density lipoprotein cholesterol and apolipoprotein B levels with increased odds ratio (OR) of 14.6 (95% CI 4.57-46.4) per 1 mmol/L lower FPG for MASLD and OR of 2.92 (95% CI 1.78-4.81) for coronary artery disease (CAD). Genetically-proxied GK activation was associated with decreased risk of CAD (OR 0.69, 95% CI 0.54-0.88) and not with dyslipidemia. One-sample MR validation in HKDR showed consistent results.
CONCLUSIONS
Impaired GK-GKRP interaction, rather than direct GK activation, may worsen lipid profiles and increase risks of MASLD and CAD. Development of future GKAs should avoid interfering with GK-GKRP interaction.
Topics: Mendelian Randomization Analysis; Humans; Genome-Wide Association Study; Adaptor Proteins, Signal Transducing; Risk Factors; Genetic Predisposition to Disease; Risk Assessment; Blood Glucose; Glucokinase; Biomarkers; Lipids; Phenotype; Carrier Proteins; Polymorphism, Single Nucleotide; Time Factors; Dyslipidemias; Fatty Liver
PubMed: 38951793
DOI: 10.1186/s12933-024-02321-z -
Acta Diabetologica Jul 2024Cerebrovascular accidents (CVA) represent a major complication in diabetes (DM). Real-life evidence as to whether modern management of CVA and DM have softened this...
BACKGROUND
Cerebrovascular accidents (CVA) represent a major complication in diabetes (DM). Real-life evidence as to whether modern management of CVA and DM have softened this relationship is limited. Therefore, we estimated prevalence and impact of DM on in-hospital survival and complications in a contemporary cohort of subjects with CVA.
METHODS
We retrospectively evaluated the records of 937 patients admitted for CVA at the Stroke Unit of Verona University Hospital during a 3-year period. Pre-existing or de novo DM was ascertained by prior diagnosis, glucose-lowering therapy at admission/discharge or admittance plasma glucose ≥ 200 mg/dL. Multiple regressions were applied to test DM as predictor of in-hospital mortality, complications (composite of infections, cardio- and cerebrovascular complications, major bleeding and pulmonary complications), duration and costs of hospitalization.
RESULTS
Diabetes prevalence was 21%, of which 22% de novo diagnoses. Compared to non-DM, diabetic individuals were older and carried an increased burden of cardiovascular risk factors. Compared to known DM, de novo DM individuals were younger, had higher admittance plasma glucose and poorer cardiovascular comorbidities. Overall, DM versus non-DM individuals did not show significantly increased risk of death (14.0 vs. 9.3%; crude-OR 1.59 95% CI 0.99-2.56). Controlling for confounders did not improve significance. DM resulted independent predictor for in-hospital complications (36.2% vs. 26.9%; adj-OR 1.49, 1.04-2.13), but not for duration and costs of hospitalization.
CONCLUSION
DM frequently occurs in patients admitted for stroke and carries an excess burden of adverse in-hospital complications, urgently calling for strategies to anticipate DM diagnosis and tailored treatment in high-risk individuals.
PubMed: 38951223
DOI: 10.1007/s00592-024-02318-w -
Diabetologia Jun 2024The increasing incidence of type 2 diabetes, which represents 90% of diabetes cases globally, is a major public health concern. Improved glucose management reduces the... (Review)
Review
The increasing incidence of type 2 diabetes, which represents 90% of diabetes cases globally, is a major public health concern. Improved glucose management reduces the risk of vascular complications and mortality; however, only a small proportion of the type 2 diabetes population have blood glucose levels within the recommended treatment targets. In recent years, diabetes technologies have revolutionised the care of people with type 1 diabetes, and it is becoming increasingly evident that people with type 2 diabetes can also benefit from these advances. In this review, we describe the current knowledge regarding the role of technologies for people living with type 2 diabetes and the evidence supporting their use in clinical practice. We conclude that continuous glucose monitoring systems deliver glycaemic benefits for individuals with type 2 diabetes, whether treated with insulin or non-insulin therapy; further data are required to evaluate the role of these systems in those with prediabetes (defined as impaired glucose tolerance and/or impaired fasting glucose and/or HbA levels between 39 mmol/mol [5.7%] and 47 mmol/mol [6.4%]). The use of insulin pumps seems to be safe and effective in people with type 2 diabetes, especially in those with an HbA significantly above target. Initial results from studies exploring the impact of closed-loop systems in type 2 diabetes are promising. We discuss directions for future research to fully understand the potential benefits of integrating evidence-based technology into care for people living with type 2 diabetes and prediabetes.
PubMed: 38951212
DOI: 10.1007/s00125-024-06203-7 -
Zhonghua Yi Xue Za Zhi Jul 2024To investigate the risk factors of venous thrombosis in patients with polycythemia vera (PV) and establish a prediction model for venous thrombosis. PV patients with...
To investigate the risk factors of venous thrombosis in patients with polycythemia vera (PV) and establish a prediction model for venous thrombosis. PV patients with JAK2 gene mutation positive in the Second Hospital of Tianjin Medical University from September 2017 to November 2023 were retrospectively included. The patients were divided into groups according to whether they had venous thrombosis. After matching age and gender factors with propensity scores, 102 patients were included in the venous thrombosis group [46 males, 56 females, with a median age (, ) of 52 (44, 60) years] and 204 cases were included in the group without venous thrombosis [92 males, 112 females, with a median age of 52 (44, 59) years]. The clinical and laboratory characteristics, disease progression and incidence of gene mutation were compared between the two groups. The follow-up cohort ended on November 20, 2023, with a median follow-up [ (, )] of 11 (1, 53) years. Multivariate Cox risk model was used to analyze the influencing factors of venous thrombosis in PV patients, and establish a scoring system for the venous thrombosis risk factor prediction model of PV patients. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency of the model. Hemoglobin concentration, the ratio of hematopoietic volume≥55%, neutrophil to lymphocyte ratio≥5, hypertension, subcostal spleen≥5 cm and secondary myelofibrosis in venous thrombosis group were higher than those in non-venous thrombosis group (all <0.05). In addition, the proportion of history of thromboembolism, V617F gene mutation load (V617F%)≥50%, diabetes mellitus, ASXL1 mutation and secondary reticular silver staining≥3 in the venous thrombosis group were higher than those in the non-venous thrombosis group (all <0.05). The proportion of PV patients with 3 or more gene mutations was 44.1% (45/102) in venous thrombosis group, which was higher than that of PV patients without venous thrombosis 29.9% (61/204) (=0.014). The proportion of ASXL1 gene mutation in venous thrombosis group was 17.6% (18/102), which was higher than the 4.9% (10/204) in non-venous thrombosis group (<0.001). Multivariate Cox risk model analysis showed that previous thromboembolism history (2.031, 95%: 1.297-3.179, =0.002), V617F%≥50% (2.141 95%: 1.370-3.347, 0.001), ASXL1 mutation (=4.632, 95%: 1.497-14.336, =0.008), spleen subcostal≥5 cm (=1.771, 95% 1.047-2.996, =0.033) are the risk factors of venous thrombosis in PV patients. According to values, a score system for predicting risk of venous thrombosis in PV patients was established: previous history of thromboembolism, V617F%≥50% and spleen subcostoal≥5 cm were assigned 1 point respectively, and ASXL1 mutation was assigned 2 points. Low risk group: score 0, medium risk group: score 1-2, high risk group: score≥3. The ROC curve analysis of the model for predicting venous thrombosis in PV patients showed that the area under the curve (AUC) was 0.807 (95% 0.755-0.860), with the sensitivity of 88.2% and the specificity of 59.8% when the Youden index was 0.48. Previous thromboembolism history, V617F%≥50%, ASXL1 mutation, spleen subcostoal≥5 cm are risk factors of venous thrombosis in PV patients. The established prediction model has good prediction efficiency.
Topics: Humans; Polycythemia Vera; Male; Risk Factors; Middle Aged; Female; Venous Thromboembolism; Adult; Janus Kinase 2; Mutation; Venous Thrombosis
PubMed: 38951106
DOI: 10.3760/cma.j.cn112137-20240304-00476 -
Zhonghua Nei Ke Za Zhi Jul 2024
Topics: Humans; Hypokalemic Periodic Paralysis; Diabetes Mellitus, Type 2; Pedigree; Male; Adult; Female; Mutation; Insulin
PubMed: 38951094
DOI: 10.3760/cma.j.cn112138-20231019-00230 -
Zhonghua Fu Chan Ke Za Zhi Jun 2024To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the...
To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization. The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed. (1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all >0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); =28.397, <0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all <0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); =0.001, =0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); =56.132, <0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); =41.377, <0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; =2.184, =0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all >0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm and cone size <2 cm were higher than that in the control group (all <0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference (=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm (=3.084, 95%: 1.474-6.453; =0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm and those with cone size ≥2 cm (=1.700, 95%: 0.935-3.092; =0.077). The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.
Topics: Humans; Female; Pregnancy; Conization; Pregnancy Outcome; Premature Birth; Adult; Fetal Membranes, Premature Rupture; Cervix Uteri; Pregnancy Complications; Retrospective Studies; Infant, Newborn; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 38951080
DOI: 10.3760/cma.j.cn112141-20240202-00072 -
BMJ Open Jul 2024Children and adolescents with recent-onset type 1 diabetes (T1D) commonly maintain a certain level of insulin production during the remission phase, which can last...
INfluenza VaccInation To mitigate typE 1 Diabetes (INVITED): a study protocol for a randomised, double-blind, placebo-controlled clinical trial in children and adolescents with recent-onset type 1 diabetes.
INTRODUCTION
Children and adolescents with recent-onset type 1 diabetes (T1D) commonly maintain a certain level of insulin production during the remission phase, which can last months to years. Preserving β-cell function can reduce T1D complications and improve glycaemic control. Influenza vaccination has pleiotropic effects and administration of the vaccine during the early phases of T1D may offer β-cell protection. This study aims to assess the effect of influenza vaccination on preserving β-cell function in children and adolescents with recent-onset T1D.
METHODS AND ANALYSIS
The INfluenza VaccInation To mitigate typE 1 Diabetes trial is a randomised, double-blind, placebo-controlled, multicentre trial in paediatric patients with recent-onset T1D aged 7-17 years. 100 participants will be randomised in a 1:1 ratio to receive either a standard inactivated quadrivalent influenza vaccine or a placebo within 14 days of diagnosis. The primary outcome is a difference in mean change (from baseline to 12 months) in C-peptide level between groups during a 2-hour mixed-meal tolerance test. Secondary outcomes include mean change (from baseline to 6 months) in C-peptide levels, haemoglobin A1c, ambulatory glucose profiles and insulin requirements. Exploratory outcomes are diabetes-related autoantibodies, inflammatory markers and serum haemagglutinin inhibition antibody titres against the influenza viruses. The current treatment for T1D is largely symptomatic, relying on insulin administration. There is a pressing need for novel pharmacological approaches aimed at modulating the immune system to preserve residual β-cell function. Existing immunotherapies are cost-prohibitive and associated with multiple side effects, whereas influenza vaccination is inexpensive and generally well tolerated. A positive outcome of this study holds potential for immediate implementation into standard care for children and adolescents with recent-onset T1D and may guide future research on immune modulation in T1D.
ETHICS AND DISSEMINATION
Ethical approval was obtained from Danish Health Authorities prior to participant enrollment. The trial results will be submitted to a peer-reviewed journal.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov NCT05585983 and EudraCT Number 2022-500906-17-01.
Topics: Humans; Diabetes Mellitus, Type 1; Adolescent; Child; Influenza Vaccines; Double-Blind Method; Female; Male; Influenza, Human; Glycated Hemoglobin; C-Peptide; Randomized Controlled Trials as Topic; Blood Glucose; Insulin; Vaccination; Insulin-Secreting Cells
PubMed: 38950997
DOI: 10.1136/bmjopen-2024-084808 -
Cleveland Clinic Journal of Medicine Jul 2024Despite current therapies, heart failure and chronic kidney disease continue to be major causes of morbidity and mortality. Sodium-glucose cotransporter 2 (SGLT-2)... (Review)
Review
Despite current therapies, heart failure and chronic kidney disease continue to be major causes of morbidity and mortality. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have recently become standard-of-care therapy for these conditions. This review summarizes important randomized controlled trials of SGLT-2 inhibitors and guidelines for using these agents in patients with heart failure and chronic kidney disease in both clinic and hospital settings.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Heart Failure; Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2; Randomized Controlled Trials as Topic
PubMed: 38950981
DOI: 10.3949/ccjm.91a.23093 -
Cleveland Clinic Journal of Medicine Jul 2024
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic; Gout; Heart Failure; Hypoglycemic Agents
PubMed: 38950980
DOI: 10.3949/ccjm.91b.07024