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BMJ Open Diabetes Research & Care Jun 2024We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2... (Randomized Controlled Trial)
Randomized Controlled Trial
Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial (PRISM-RCT) in Chinese patients with young-onset diabetes: design, methods and baseline characteristics.
INTRODUCTION
We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines.
RESEARCH DESIGN AND METHODS
In this 3-year Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial, we evaluate the effects of a multicomponent care model integrating use of information and communication technology (Joint Asia Diabetes Evaluation (JADE) platform), biogenetic markers and patient-reported outcome measures in patients with T2D diagnosed at ≤40 years of age and aged ≤50 years. The JADE-PRISM group received 1 year of specialist-led team-based management using treatment algorithms guided by biogenetic markers (genome-wide single-nucleotide polymorphism arrays, exome-sequencing of 34 monogenic diabetes genes, C-peptide, autoantibodies) to achieve multiple treatment goals (glycated hemoglobin (HbA1c) <6.2%, blood pressure <120/75 mm Hg, low-density lipoprotein-cholesterol <1.2 mmol/L, waist circumference <80 cm (women) or <85 cm (men)) in a diabetes center setting versus usual care (JADE-only). The primary outcome is incidence of all diabetes-related complications.
RESULTS
In 2020-2021, 884 patients (56.6% men, median (IQR) diabetes duration: 7 (3-12) years, current/ex-smokers: 32.5%, body mass index: 28.40±5.77 kg/m, HbA1c: 7.52%±1.66%, insulin-treated: 27.7%) were assigned to JADE-only (n=443) or JADE-PRISM group (n=441). The profiles of the whole group included positive family history (74.7%), general obesity (51.4%), central obesity (79.2%), hypertension (66.7%), dyslipidemia (76.4%), albuminuria (35.4%), estimated glomerular filtration rate <60 mL/min/1.73 m (4.0%), retinopathy (13.8%), atherosclerotic cardiovascular disease (5.2%), cancer (3.1%), emotional distress (26%-38%) and suboptimal adherence (54%) with 5-item EuroQol for Quality of Life index of 0.88 (0.87-0.96). Overall, 13.7% attained ≥3 metabolic targets defined in secondary outcomes. In the JADE-PRISM group, 4.5% had pathogenic/likely pathogenic variants of monogenic diabetes genes; 5% had autoantibodies and 8.4% had fasting C-peptide <0.2 nmol/L. Other significant events included low/large birth weight (33.4%), childhood obesity (50.7%), mental illness (10.3%) and previous suicide attempts (3.6%). Among the women, 17.3% had polycystic ovary syndrome, 44.8% required insulin treatment during pregnancy and 17.3% experienced adverse pregnancy outcomes.
CONCLUSIONS
Young-onset diabetes is characterized by complex etiologies with comorbidities including mental illness and lifecourse events.
TRIAL REGISTRATION NUMBER
NCT04049149.
Topics: Humans; Female; Male; Diabetes Mellitus, Type 2; Adult; Precision Medicine; Insulin Secretion; Middle Aged; China; Age of Onset; Young Adult; Insulin; Hypoglycemic Agents; Follow-Up Studies; Blood Glucose; Glycated Hemoglobin; Asian People; Biomarkers; Prognosis; East Asian People
PubMed: 38901858
DOI: 10.1136/bmjdrc-2024-004120 -
Journal of Global Health Jun 2024The reallocation of health care services during the coronavirus disease 2019 (COVID-19) pandemic disrupted the continuity of primary care. This study examines the... (Observational Study)
Observational Study
BACKGROUND
The reallocation of health care services during the coronavirus disease 2019 (COVID-19) pandemic disrupted the continuity of primary care. This study examines the repercussions of the COVID-19 pandemic on clinical indicators within the Catalan population, emphasising individuals with chronic conditions. It provides insights into mortality and transfer rates considering intersectional perspectives.
METHODS
We designed a retrospective, observational population-based cohort study based on routinely collected data from January 2015 to June 2021 for all individuals available in the Information System for Research in Primary Care (Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (SIDIAP)), the largest public primary care database in Catalonia, Spain. We included 6 301 095 individuals, constituting 81.6% of Catalonia's population in 2020. To perform a repeated measurements analysis of the indicators, we focussed on individuals who had one or more indicators in both the pre-pandemic (January 2015 to March 2020) and pandemic periods (March 2020 to June 2021), and those diagnosed with type 2 diabetes mellitus (T2D), high blood pressure, and heart failure. We selected key clinical indicators for analysis, including systolic and diastolic blood pressure, body mass index (BMI), cholesterol (total, high, and low-density lipoprotein), triglycerides, glycosylated haemoglobin, the Barthel index, and cardiovascular risk (Registre Gironí del cor (REGICOR) index).
RESULTS
Mortality and transfer rates increased during the pandemic, contributing to a decline in the active population in the public health system. We also observed a reduction in pandemic period prevalence of patients with chronic conditions: -26.7% for heart failure, -15.1% for high blood pressure, and -14.6% for T2D. In both pre-pandemic and pandemic periods, 1 632 013 subjects had at least one clinical indicator record. Clinical indicators worsened in patients diagnosed with chronic conditions during the pandemic. Most indicators worsened, with differences between men and women (+9.4% vs +3.7% for the REGICOR index and -14.1% vs -16.6% for the Barthel index in men and in women, respectively), and to a similar extent (or greater in some cases) in individuals without these conditions.
CONCLUSIONS
We used longitudinal data to assess the repercussions of the COVID-19 pandemic on population health while considering a wide range of clinical indicators and socioeconomic determinants. Our analysis shows a deterioration in clinical indicators during the pandemic, particularly in cardiometabolic factors, underscoring the importance of continuous primary care for individuals with chronic conditions.
Topics: Humans; COVID-19; Spain; Retrospective Studies; Chronic Disease; Female; Male; Middle Aged; Aged; Adult; Diabetes Mellitus, Type 2; SARS-CoV-2; Cohort Studies; Heart Failure; Hypertension; Aged, 80 and over; Primary Health Care
PubMed: 38900506
DOI: 10.7189/jogh.14.05020 -
Bioscience Reports Jun 2024Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL)-like particle in which the apolipoprotein B component is covalently linked to apolipoprotein(a). Lp(a) is a...
Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL)-like particle in which the apolipoprotein B component is covalently linked to apolipoprotein(a). Lp(a) is a well-established independent risk factor for cardiovascular diseases. Plasma lipoprotein(a) concentrations vary enormously between individuals and ethnic groups. Several nucleotide polymorphisms in the SLC22A3 gene associate with Lp(a) concentration in people of different ethnicities. We investigated the association of a Polynesian-specific (Māori and Pacific peoples) SLC22A3 gene coding variant p.Thr44Met) with the plasma concentration of Lp(a) in a cohort of 302 healthy Polynesian males. An apolipoprotein(a)-size independent assay assessed plasma lipoprotein(a) concentrations, all other lipid and apolipoprotein concentrations were measured using standard laboratory techniques. Quantitative real-time polymerase chain reaction was used to determine apolipoprotein(a) isoforms. The range of metabolic (HbA1c, blood pressure and blood lipids) and blood lipid variables were similar between the non-carriers and carriers in age, ethnicity and BMI adjusted models. However, rs8187715 SLC22A3 variant was significantly associated with lower lipoprotein(a) concentrations. Median lipoprotein(a) concentration was 10.60 nmol/L (IQR 5.40 to 41.00) in non-carrier group, and was 7.60 nmol/L (IQR 5.50 to 12.10) in variant carrier group (p <0.05). Lp(a) concentration inversely correlated with apolipoprotein(a) isoform size. After correction for apolipoprotein(a) isoform size, metabolic parameters and ethnicity, the association between the SLC22A3 variant and plasma Lp(a) concentration remained. This study is the first to identify the association of this gene variant and low plasma Lp(a) concentrations. This provides evidence for better guidance on ethnic specific cut-offs when defining "elevated" and "normal" plasma Lp(a) concentrations in clinical applications.
PubMed: 38896441
DOI: 10.1042/BSR20240403 -
Journal of Cellular and Molecular... Jun 2024Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly...
Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD-free individuals were enrolled in this case-control study. The rs1801133 variant was genotyped by PCR-RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD-free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs-CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.
Topics: Humans; Homocysteine; Male; Coronary Artery Disease; Middle Aged; Female; Case-Control Studies; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Single Nucleotide; Severity of Illness Index; Aged; Risk Factors; Genetic Predisposition to Disease; ROC Curve; Genotype; C-Reactive Protein; Alleles; Apolipoprotein A-I
PubMed: 38896027
DOI: 10.1111/jcmm.18474 -
Animal Models and Experimental Medicine Jun 2024Apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for late-onset Alzheimer's disease, and it can aggravate depressive symptoms in non-AD patients....
BACKGROUND
Apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for late-onset Alzheimer's disease, and it can aggravate depressive symptoms in non-AD patients. However, the impact of ApoE4 on AD-associated depression-like behaviors and its underlying pathogenic mechanisms remain unclear.
METHODS
This study developed a 5xFAD mouse model overexpressing human ApoE4 (E4FAD). Behavioral assessments and synaptic function tests were conducted to explore the effects of ApoE4 on cognition and depression in 5xFAD mice. Changes in peripheral and central lipid metabolism, as well as the levels of serotonin (5-HT) and γ-aminobutyric acid (GABA) neurotransmitters in the prefrontal cortex, were examined. In addition, the protein levels of 24-dehydrocholesterol reductase/glycogen synthase kinase-3 beta/mammalian target of rapamycin (DHCR24/GSK3β/mTOR) and postsynaptic density protein 95/calmodulin-dependent protein kinase II/brain-derived neurotrophic factor (PSD95/CaMK-II/BDNF) were measured to investigate the molecular mechanism underlying the effects of ApoE4 on AD mice.
RESULTS
Compared with 5xFAD mice, E4FAD mice exhibited more severe depression-like behaviors and cognitive impairments. These mice also exhibited increased amyloid-beta deposition in the hippocampus, increased astrocyte numbers, and decreased expression of depression-related neurotransmitters 5-HT and GABA in the prefrontal cortex. Furthermore, lipid metabolism disorders were observed in E4FAD, manifesting as elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol in peripheral blood, decreased cholesterol level in the prefrontal cortex, and reduced expression of key enzymes and proteins related to cholesterol synthesis and homeostasis. Abnormal expression of proteins related to the DHCR24/GSK3β/mTOR and PSD95/CaMK-II/BDNF pathways was also observed.
CONCLUSION
This study found that ApoE4 overexpression exacerbates depression-like behaviors in 5xFAD mice and confirmed that ApoE4 reduces cognitive function in these mice. The mechanism may involve the induction of central and peripheral lipid metabolism disorders. Therefore, modulating ApoE expression or function to restore cellular lipid homeostasis may be a promising therapeutic target for AD comorbid with depression. This study also provided a better animal model for studying AD comorbid with depression.
PubMed: 38895818
DOI: 10.1002/ame2.12446 -
Clinical Cardiology Jun 2024Statins are lipid-lowering drugs with favorable anti-inflammatory effects. This study aimed to explore different statin-based lipid-lowering strategies to reduce... (Comparative Study)
Comparative Study
BACKGROUND
Statins are lipid-lowering drugs with favorable anti-inflammatory effects. This study aimed to explore different statin-based lipid-lowering strategies to reduce high-sensitivity C-reactive protein (hs-CRP).
HYPOTHESIS
The hypothesis is that different statin-based lipid-lowering strategies might reduce hs-CRP.
METHODS
This retrospective study included 3653 patients who underwent percutaneous coronary intervention (PCI). Three statin-based lipid-lowering strategies were investigated, including different types of statins (atorvastatin vs. rosuvastatin), statin combined with ezetimibe therapy (vs. without), and intensive statin therapy (vs. regular). The hs-CRP levels and blood lipid indicators were measured at baseline and after 1-month lipid-lowering therapy. Multivariable linear regression analysis and structural equation mode analysis were conducted to verify the association between different lipid-lowering strategies, Δhs-CRP (%) and ΔLDL-C (%).
RESULTS
Totally, 3653 patients were enrolled with an average age of 63.81 years. Multivariable linear regression demonstrated that statin combined with ezetimibe therapy was significantly associated with decreased Δhs-CRP (%) (β = -0.253, 95% CI: [-0.501 to -0.005], p = 0.045). The increased ΔLDL-C (%) was an independent predictor of elevated levels of Δhs-CRP (%) (β = 0.487, 95% CI: [0.15-0.824], p = 0.005). Furthermore, structural equation model analysis proved that statin combined with ezetimibe therapy (β = -0.300, p < 0.001) and intensive statin therapy (β = -0.032, p = 0.043) had an indirect negative effect on Δhs-CRP via ΔLDL-C.
CONCLUSIONS
Compared with routine statin use, statin combined with ezetimibe therapy and intensive statin therapy could further reduce hs-CRP levels.
Topics: Humans; Male; Retrospective Studies; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; C-Reactive Protein; Coronary Artery Disease; Middle Aged; Biomarkers; Treatment Outcome; Percutaneous Coronary Intervention; Ezetimibe; Drug Therapy, Combination; Aged; Rosuvastatin Calcium; Atorvastatin; Cholesterol, LDL; Anticholesteremic Agents; Dyslipidemias
PubMed: 38895772
DOI: 10.1002/clc.24301 -
Frontiers in Public Health 2024Habitual substance use, i. e., alcohol, tobacco and betel nut, has been found with an increased risk of metabolic syndrome (MetS) in the general population, whereas the...
BACKGROUNDS
Habitual substance use, i. e., alcohol, tobacco and betel nut, has been found with an increased risk of metabolic syndrome (MetS) in the general population, whereas the association remains unclear in physically fit military personnel. This study aimed to investigate the combination of these substances use and their associations with new-onset MetS in the military.
METHODS
A total of 2,890 military men and women, aged 18-39 years, without MetS were obtained from the cardiorespiratory fitness and health in eastern armed forces study (CHIEF) in Taiwan and followed for incident MetS from baseline (2014) through the end of 2020. Incident MetS event was defined by the International Diabetes Federation guideline and confirmed in the annual health examinations. A self-report was used to assess the alcohol, tobacco and betel nut use status (active vs. former/never). Multivariable Cox regression model was performed to determine the association with adjustments for sex, age, body mass index and physical activity at baseline.
RESULTS
At baseline, there were 279 active betel nut chewers (9.7%), 991 active smokers (34.3%) and 1,159 active alcohol consumers (40.1%). During a mean follow-up of 6.0 years, 673 incident MetS (23.3%) were observed. As compared to no substance users, only one substance, and two and three substances users had a greater risk of incident MetS [hazard ratios (HRs) and 95% confidence intervals: 1.27 (1.06-1.54), 1.38 (1.12-1.69) and 1.78 (1.37-2.32), respectively]. In subgroup analyses, the risk of incident MetS in two and three substances users was significantly greater in those free of baseline low high-density lipoprotein [HRs: 1.54 (1.21-1.95) and 2.57 (1.92-3.46), respectively], as compared to their counterparts (both p for interactions <0.05).
CONCLUSION
A dose-response association of more substances use for new-onset MetS was noted in military personnel. This finding suggests that the combined alcohol, tobacco and betel nut use may play a role in the development of MetS. Further study is required to establish causation and to investigate the potential benefits of substance use cessation in reducing the risk of MetS.
Topics: Humans; Male; Female; Adult; Military Personnel; Metabolic Syndrome; Taiwan; Incidence; Young Adult; Adolescent; Alcohol Drinking; Substance-Related Disorders; Risk Factors; Areca; Cohort Studies
PubMed: 38894993
DOI: 10.3389/fpubh.2024.1406524 -
Iranian Journal of Public Health Feb 2024Ischemic stroke (IS) is the leading cause of disability and mortality worldwide. Low-density lipoprotein cholesterol (LDL-C) levels hadno potential risk on ischemic...
BACKGROUND
Ischemic stroke (IS) is the leading cause of disability and mortality worldwide. Low-density lipoprotein cholesterol (LDL-C) levels hadno potential risk on ischemic stroke. However, higher LDL-C levels were closely related to IS. Based on two antagonistic viewpoints, a Mendelian randomization (MR) study was designed to evaluate the causal effects of LDL-C levels on IS.
METHODS
Datasets of LDL-C levels and ischemic stroke were acquired from genome-wide association studies (GWAS). Weighted median method was conducted for main analysis, and MR-Egger and inverse-variance weighted (IVW) methods were performed for auxiliary analyses. Heterogeneity and pleiotropic tests were utilized to confirm the reliability of this study.
RESULTS
A total of 359 single nucleotide polymorphisms (SNPs) were associated with LDL-C levels ( < 5 × 10) and 337 SNPs were available in ischemic stroke with eliminating outliers. LDL-C levels were significantly associated with ischemic stroke (OR = 1.104, 95%CI = 1.019 - 1.195, = 1.52 × 10). MR-Egger and IVW showed directionally similar estimates (MR-Egger: OR = 1.120, 95%CI = 1.040 - 1.207, = 3.12 × 10; IVW: OR = 1.120, 95%CI = 1.064 - 1.178, = 1.17 × 10).
CONCLUSION
LDL-C levels had causal effects on IS, providing insights into the design of future interventions to reduce the burden of ischemic stroke.
PubMed: 38894840
DOI: 10.18502/ijph.v53i2.14924 -
Journal of Clinical Medicine May 2024: Psoriasis is a common, T-cell-mediated inflammatory and immune-mediated skin disease. Numerous studies confirmed that patients with psoriasis have a significant...
: Psoriasis is a common, T-cell-mediated inflammatory and immune-mediated skin disease. Numerous studies confirmed that patients with psoriasis have a significant frequency of cardiovascular (CV) risk factors and CV diseases (CVDs). Risk stratification is helpful in light of the elevated risk of CVD in psoriasis patients. SCORE2 and SCORE2-OP, a new algorithm derived, calibrated and validated to predict the 10-year risk of first-onset CVD in European populations, enhances the identification of individuals at higher risk of developing CVD across Europe. : Using the SCORE2 and SCORE2-OP scoring systems, the current study objective was to evaluate CV risk in Slovak psoriasis patients and the relationship between CV risk and psoriasis features in a real-world setting. : A case-control study was conducted involving 115 outpatients with plaque psoriasis and 66 age- and gender-matched controls with skin conditions other than psoriasis. Patients with psoriasis had significantly higher mean SCORE2 values. In the age group up to 50 years, more psoriasis patients were classified as moderate risk than controls (33.8% vs. 13.6%, = 0.010); the high-risk category was dominated by psoriasis patients. Analysing the relationship between CV risk and selected variables, we determined, using linear regression, the dependence of the SCORE2 risk score on gender in the age group up to 50 years, on age in both age groups, on waist circumference (WC) in the category up to 50 years and on the duration and severity of psoriasis in both age groups using linear regression. For individuals older than 70, we estimated the SCORE2-OP risk score, with the average risk score being 19.5 ± 4.95. We did not observe controls with a high risk score. Psoriasis patients were more likely to be smokers and had significantly higher mean values for body mass index (BMI), WC, total cholesterol (TC), low-density lipoprotein (LDL) and systolic blood pressure (BP). : Because CV risk factors and psoriasis are strongly related, the importance of CV risk stratification is growing, and initiating preventive lifestyle changes or therapeutic interventions in patients with psoriasis is warranted.
PubMed: 38892947
DOI: 10.3390/jcm13113237 -
Journal of Clinical Medicine May 2024: Obesity is linked to higher rates of complications; lower absolute recovery of mobility, pain, and function; and increased costs of care following total knee or hip...
: Obesity is linked to higher rates of complications; lower absolute recovery of mobility, pain, and function; and increased costs of care following total knee or hip arthroplasty (TKA, THA). The aim of this prospective cohort study was to evaluate the effectiveness of a 12-week partial meal replacement (PMR) weight loss program for people awaiting TKA or THA and living with obesity (body mass index (BMI) ≥ 30 kg/m). : The intervention was delivered remotely and included a 12-week PMR plan of 1200 calories/day, incorporating two meal replacement shakes/soups and a third suitable simple meal option. The intervention support was provided through online group education sessions, one-to-one teleconsultation with a dietitian, and access to a structured PMR App with functions for goal setting and providing educational content on diet, physical activity, and behaviour changes. : Of the 182 patients approached, 29 provided consent to participate, 26 participants commenced the program, and 22 participants completed the 12-week PMR plan. Completers exhibited statistically significant weight loss from baseline to 12 weeks, with a paired difference of 6.3 kg (95% CI: 4.8, 7.7; < 0.001), with 15 out of 22 (68.2%) participants achieving at least 5% weight loss. Statistically significant reductions in HbA1c and low density lipoprotein (LDL) were observed at 12 weeks compared to baseline. Moreover, a significant increase in the proportion of participants in the action and maintenance phases of the readiness to change diet, physical activity, and weight were observed at 12 weeks. The majority of program completers (18 out of 22) expressed willingness to pay for the service if offered on a long-term basis following the arthroplasty. : This study's findings demonstrated that significant weight loss is achievable for people living with obesity awaiting arthroplasty following a 12-week PMR weight loss program. The remote delivery of the intervention was feasible and well accepted by people awaiting TKA or THA.
PubMed: 38892938
DOI: 10.3390/jcm13113227