ABSTRACT
Due to increased life expectancy and lifestyle changes, the prevalence of diabetes among the elderly in Korea is continuously rising, as is the associated public health burden. Diabetes management in elderly patients is complicated by age-related physiological changes, sarcopenia characterized by loss of muscle mass and function, comorbidities, and varying levels of functional, cognitive, and mobility abilities that lead to frailty. Moreover, elderly patients with diabetes frequently face multiple chronic conditions that elevate their risk of cardiovascular diseases, cancer, and mortality; they are also prone to complications such as hyperglycemic hyperosmolar state, diabetic ketoacidosis, and severe hypoglycemia. This review examines the characteristics of and management approaches for diabetes in the elderly, and advocates for a comprehensive yet personalized strategy.
Subject(s)
Diabetes Mellitus, Type 2 , Precision Medicine , Humans , Diabetes Mellitus, Type 2/therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Aged , Precision Medicine/methods , Republic of Korea/epidemiology , Hypoglycemic Agents/therapeutic use , Sarcopenia/therapy , Holistic Health , Aged, 80 and over , Comorbidity , Aging/physiologyABSTRACT
Genetic testing is recommended for all patients with pheochromocytomas and paragangliomas (PPGL) to establish genotype-phenotype associations. We investigated germline mutations in 59 patients with PPGL at six Korean university hospitals using next-generation sequencing (NGS) targeting 38 PPGL-associated genes, including those recommended by the Korean PPGL Task Force. Germline mutations were identified in 13 patients (22%), and affected four genes: RET, NF1, VHL, and SDHD. Germline mutations were significantly associated with a family history of PPGL, smaller tumor size, and the presence of other types of tumors. Using 95 Korean PPGL cases with germline mutations identified through a literature review and 13 cases from our cohort, we characterized genotype-phenotype correlations. Mutation hotspots were identified in specific codons of RET (codons 631 and 634), VHL (157 and 167), and SDHB (131 and 253). NF1 mutations varied, indicating the absence of common hotspots. These findings highlight the efficacy of the recommended NGS panel for Korean patients with PPGL and the importance of genetic testing in establishing clinical management and personalized therapeutic strategies.
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AIMS: Gout is associated with a significant burden of cardiovascular disease. The aim of this study was to evaluate the impact of a favorable lifestyle on incident cardiovascular events in patients with gout. METHODS: We identified 9 110 patients with gout from the UK Biobank cohort based on self-report and/or hospital diagnostic codes. Lifestyle behaviors, including smoking status, physical activity, obesity, and diet, were categorized into three patterns: favorable (3-4 healthy factors), intermediate (2 healthy factors), and unfavorable (0-1 healthy factor). The cardiovascular risk of participants with and without gout was estimated based on their serum uric acid levels and lifestyle patterns. RESULTS: Among 9 110 patients with gout and 457 596 participants without gout, the median follow-up duration was 8.9 years. The incidence rate of cardiovascular disease was significantly higher in the gout population than in the non-gout population (11.38 vs 5.49 per 1000 person-years). The gout population consistently exhibited a high cardiovascular risk, irrespective of uric acid levels, whereas a positive correlation was observed between uric acid levels and cardiovascular risk in the non-gout population. Adopting a favorable lifestyle pattern was associated with a lower risk of cardiovascular disease in both gout and non-gout populations. Across all categories of uric acid, a favorable lifestyle was found to reduce cardiovascular risk in patients with gout. CONCLUSION: Patients with gout remain at high risk of developing cardiovascular disease despite having normal uric acid levels. Lifestyle modifications may represent an effective and cost-efficient therapeutic approach for preventing cardiovascular events in this population.
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BACKGROUND: Glaucoma is a leading cause of worldwide irreversible blindness. Considerable uncertainty remains regarding the association between a variety of phenotypes and the genetic risk of glaucoma, as well as the impact they exert on the glaucoma development. METHODS: We investigated the associations of genetic liability for primary open angle glaucoma (POAG) with a wide range of potential risk factors and to assess its impact on the risk of incident glaucoma. The phenome-wide association study (PheWAS) approach was applied to determine the association of POAG polygenic risk score (PRS) with a wide range of phenotypes in 377, 852 participants from the UK Biobank study and 43,623 participants from the Penn Medicine Biobank study, all of European ancestry. Participants were stratified into four risk tiers: low, intermediate, high, and very high-risk. Cox proportional hazard models assessed the relationship of POAG PRS and ocular factors with new glaucoma events. RESULTS: In both discovery and replication set in the PheWAS, a higher genetic predisposition to POAG was specifically correlated with ocular disease phenotypes. The POAG PRS exhibited correlations with low corneal hysteresis, refractive error, and ocular hypertension, demonstrating a strong association with the onset of glaucoma. Individuals carrying a high genetic burden exhibited a 9.20-fold, 11.88-fold, and 28.85-fold increase in glaucoma incidence when associated with low corneal hysteresis, high myopia, and elevated intraocular pressure, respectively. CONCLUSION: Genetic susceptibility to POAG primarily influences ocular conditions, with limited systemic associations. Notably, the baseline polygenic risk for POAG robustly associates with new glaucoma events, revealing a large combined effect of genetic and ocular risk factors on glaucoma incidents.
Subject(s)
Glaucoma, Open-Angle , Humans , Glaucoma, Open-Angle/genetics , Glaucoma, Open-Angle/epidemiology , Intraocular Pressure , Genetic Risk Score , Biological Specimen Banks , Genome-Wide Association Study , Genetic Predisposition to Disease , Risk FactorsABSTRACT
BACKGROUND: Previous studies have shown that lifestyle/environmental factors could accelerate the development of age-related hearing loss (ARHL). However, there has not yet been a study investigating the joint association among genetics, lifestyle/environmental factors, and adherence to healthy lifestyle for risk of ARHL. We aimed to assess the association between ARHL genetic variants, lifestyle/environmental factors, and adherence to healthy lifestyle as pertains to risk of ARHL. METHODS: This case-control study included 376,464 European individuals aged 40 to 69 years, enrolled between 2006 and 2010 in the UK Biobank (UKBB). As a replication set, we also included a total of 26,523 individuals considered of European ancestry and 9834 individuals considered of African-American ancestry through the Penn Medicine Biobank (PMBB). The polygenic risk score (PRS) for ARHL was derived from a sensorineural hearing loss genome-wide association study from the FinnGen Consortium and categorized as low, intermediate, high, and very high. We selected lifestyle/environmental factors that have been previously studied in association with hearing loss. A composite healthy lifestyle score was determined using seven selected lifestyle behaviors and one environmental factor. RESULTS: Of the 376,464 participants, 87,066 (23.1%) cases belonged to the ARHL group, and 289,398 (76.9%) individuals comprised the control group in the UKBB. A very high PRS for ARHL had a 49% higher risk of ARHL than those with low PRS (adjusted OR, 1.49; 95% CI, 1.36-1.62; P < .001), which was replicated in the PMBB cohort. A very poor lifestyle was also associated with risk of ARHL (adjusted OR, 3.03; 95% CI, 2.75-3.35; P < .001). These risk factors showed joint effects with the risk of ARHL. Conversely, adherence to healthy lifestyle in relation to hearing mostly attenuated the risk of ARHL even in individuals with very high PRS (adjusted OR, 0.21; 95% CI, 0.09-0.52; P < .001). CONCLUSIONS: Our findings of this study demonstrated a significant joint association between genetic and lifestyle factors regarding ARHL. In addition, our analysis suggested that lifestyle adherence in individuals with high genetic risk could reduce the risk of ARHL.
Subject(s)
Genome-Wide Association Study , Presbycusis , Humans , Case-Control Studies , Risk Factors , Presbycusis/genetics , Healthy Lifestyle , Genetic Predisposition to DiseaseABSTRACT
BACKGRUOUND: This study investigated the effectiveness of a social networking site (SNS)-based automatic mobile message providing system on glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: A 3-month, randomized, open-label, controlled, parallel-group trial was conducted. One hundred and ten participants with T2DM were randomized to a mobile message system (MMS) (n=55) or control group (n=55). The MMS group received protocolbased automated messages two times per day for 10 weeks regarding diabetes self-management through KakaoTalk SNS messenger. The primary outcome was the difference in the change in glycated hemoglobin (HbA1c) levels (%) from baseline to week 12. RESULTS: HbA1c levels were more markedly decreased in the MMS group (8.4%±0.7% to 8.0%±1.1%) than in the control group (8.5%±0.8% to 8.4%±0.8%), resulting in a significant between-group difference (P=0.027). No differences were observed in changes in fasting glucose levels, lipid profiles, and the number of participants who experienced hypoglycemia, or in changes in lifestyle behavior between groups. However, the self-monitoring of blood glucose frequency was significantly increased in the MMS group compared to the control group (P=0.003). In addition, sleep duration was increased in the MMS group, but was not changed in the control group. CONCLUSION: An SNS-based automatic mobile message providing system was effective in improving glycemic control in patients in T2DM. Studies which based on a more individualized protocol, and investigate longer beneficial effect and sustainability will be required in the future.
Subject(s)
Diabetes Mellitus, Type 2 , Glycated Hemoglobin , Glycemic Control , Text Messaging , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/therapy , Male , Female , Middle Aged , Glycemic Control/methods , Glycated Hemoglobin/analysis , Aged , Blood Glucose/analysis , Social Networking , Self-Management/methods , Blood Glucose Self-Monitoring/methods , Cell Phone , AdultABSTRACT
BACKGRUOUND: Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population. METHODS: Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0-4), and the sum of quartiles (0-12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model. RESULTS: During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m2, and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death. CONCLUSION: Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.
Subject(s)
Cardiovascular Diseases , Myocardial Infarction , Stroke , Humans , Cardiovascular Diseases/etiology , Cohort Studies , Risk Factors , gamma-Glutamyltransferase , Guanosine TriphosphateABSTRACT
BACKGROUND: Fracture risks and associated factors are poorly understood in middle-aged and older Asian populations with inflammatory bowel disease (IBD). Therefore, we investigated fracture risk and the effects of comorbidities and lifestyle habits on the risk of developing fractures in middle-aged and older Korean patients with IBD. METHODS: We conducted a nationwide population-based cohort study using data from the National Health Insurance Corporation Database. Patients with IBD who underwent the National Screening Program and were over 40 years of age were included in the study. We compared patients with age- and sex-matched controls. The incidence of fractures, including vertebral, hip, and other sites, was determined using claims data. RESULTS: The risk of total fractures and vertebral fractures was significantly higher in the IBD group (adjusted hazard ratio [HR], 1.31, 95% confidence interval [CI], 1.16-1.48; adjusted HR, 1.59, 95% CI, 1.33-1.92, respectively). Obesity, diabetes, hypertension, and lack of exercise were associated with increased fracture risk in patients with ulcerative colitis (UC). In contrast, the risk increases in patients with Crohn's disease regardless of comorbidities and lifestyle preferences. CONCLUSION: The risk of bone fracture, especially vertebral fracture, is high in middle-aged and older Korean patients with IBD. Obesity, diabetes, hypertension, and lack of exercise are all risk factors associated with bone fractures in patients with UC. These findings are helpful for clinicians to educate patients with IBD on bone health and raise awareness of bone fractures in patients with UC who have specific risk factors.
Subject(s)
Colitis, Ulcerative , Fractures, Bone , Hypertension , Inflammatory Bowel Diseases , Spinal Fractures , Middle Aged , Humans , Aged , Adult , Cohort Studies , Inflammatory Bowel Diseases/complications , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Colitis, Ulcerative/complications , Spinal Fractures/epidemiology , Spinal Fractures/etiology , Obesity , Republic of Korea/epidemiologyABSTRACT
BACKGRUOUND: We evaluated the prevalence and management of diabetes mellitus (DM) in elderly Korean patients based on data from the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: A total of 3,068 adults aged 65 years and older (19.8% of total population) were analyzed using KNHANES from 2019 to 2020. Prevalence, awareness, treatment, and control rates, and comorbidities were analyzed. Lifestyle behaviors and energy intake were also measured. RESULTS: The prevalence of DM and prediabetes was 29.6% and 50.5%, respectively. The awareness, treatment and control rates were 76.4%, 73.3%, and 28.3%, respectively. The control rate was 77.0% if A1C <7.5% criteria was used. The mean A1C value of individuals with known DM was 7.1%, and 14.5% of the known DM patients had A1C ≥8.0%. Abdominal obesity, hypertension, and hypercholesterolemia were combined with DM in 63.9%, 71.7%, and 70.7%, respectively, and the rate of integrated management was 36.0% (A1C <7.5% criteria). A total of 40.1% of those with DM walked regularly. The percentage of energy intake from carbohydrates was higher in those with DM than in those without DM (P=0.044), while those of fat (P=0.003) and protein (P=0.025) were lower in those with DM than in those without DM in women. CONCLUSION: In 2019 to 2020, three of 10 adults aged 65 years and older in Korea had DM, and approximately 70% of them had comorbidities. A strategy for more individualized comprehensive care for the elderly patients with DM is urgently needed.
Subject(s)
Diabetes Mellitus , Adult , Aged , Humans , Female , Nutrition Surveys , Glycated Hemoglobin , Diabetes Mellitus/epidemiology , Diabetes Mellitus/diagnosis , Korea , Republic of Korea/epidemiologyABSTRACT
AIMS: We aimed to evaluate the association of prediabetes, diabetes, and diabetes duration with risk of total and site-specific cancer in the Korean population aged 65 years and above. METHODS: This study included 1,232,173 subjects aged ≥ 65 years who underwent a general health screening program. Diabetes status was categorized as normal glucose tolerance, impaired fasting glucose, new-onset diabetes, diabetes duration of < 5 years, and diabetes duration of ≥ 5 years. Cox proportional hazards models were used to investigate the association of diabetes status with cancer risk. RESULTS: The risk of total cancer increased as diabetes status worsened, as did the risks of liver, biliary, and pancreatic cancer. Risks of liver, biliary, and pancreatic cancer were significantly higher in subjects aged 65-74 years than in those aged ≥ 75 years. The relationship of diabetes status with overall cancer incidence was found to significantly interact with sex. Among subjects with diabetes, the risks of liver and lung cancer were significantly higher in men than in women regardless of diabetes duration. CONCLUSIONS: Diabetes status is associated with increased risk of cancer in the elderly. There are age and sex differences in the risk of total and site-specific cancers, including liver, biliary, and pancreatic cancer. This study highlights the importance of cancer screening for elderly subjects with diabetes.
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AIMS/INTRODUCTION: We investigated the association of polyneuropathy (PN) with all-cause and cardiovascular (CV) mortality and with cardiovascular disease (CVD) events stratified by diabetes status. MATERIALS AND METHODS: This prospective cohort study used the UK Biobank. Polyneuropathy was defined based on nurse-led interviews or ICD codes for polyneuropathy. Cox proportional hazards models were used to investigate the association of polyneuropathy with clinical outcomes. RESULTS: A total of 459,127 participants were included in the analysis. Polyneuropathy was significantly associated with all-cause and cardiovascular mortality, and with CVD events even after adjusting for CVD risk factors across all diabetes statuses. Metabolic parameters HbA1c , waist circumference, BMI and the inflammatory parameter C-reactive protein showed significant mediation effects for the association between polyneuropathy and CVD. Adherence to a favorable lifestyle was associated with a lower risk of all-cause and cardiovascular mortality regardless of polyneuropathy status. CONCLUSIONS: Polyneuropathy was associated with all-cause and cardiovascular mortality, and with CVD events in subjects with diabetes or prediabetes, even those having normal glucose tolerance. This study suggests the importance of polyneuropathy as a risk factor for death and highlights the necessity of early diagnosis and lifestyle intervention for those with type 2 diabetes and polyneuropathy.
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Polyneuropathies , Humans , Diabetes Mellitus, Type 2/complications , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Prospective Studies , Risk FactorsABSTRACT
We investigated the effects of gender and lifestyle on the association between frequency of depressive symptoms and CVD risk. The UK Biobank is a national prospective cohort study that recruited 502,505 participants aged 40-69 years between 2006 and 2010. Participants without CVD were classified as having low, moderate, high, or very high frequency of depressive symptoms according to the number of days they felt depressed in a 2-week period. UKBB data include self-reported questionnaires covering lifestyle behaviors such as smoking, physical activity, eating habits, and sleep duration. The primary outcomes included incident CVD including coronary artery disease, ischemic stroke, hemorrhagic stroke, peripheral artery disease, atrial fibrillation/flutter, and heart failure. Cox proportional hazard models were used to evaluate the effects of gender and lifestyle on the association of frequency of depressive symptoms and CVD risk. During a median follow-up of 8.9 years, 27,394 (6.3%) developed CVD. The frequency of depressive symptoms increased the risk of CVD according to low, moderate, high, and very high frequency of depressive symptoms (P for trend < 0.001). The adjusted CVD risk was 1.38-fold higher for participants with very high frequency of depressive symptoms compared to those with low frequency of depressive symptoms (HR 1.38, 95% CI 1.24-1.53, P < 0.001). The correlation between frequency of depressive symptoms and CVD risk was more remarkable in females than in males. In participants with high or very high frequency of depressive symptoms, the individual lifestyle factors of no current smoking, non-obesity, non-abdominal obesity, regular physical activity, and appropriate sleep respectively was associated with lower CVD risk by 46% (HR 0.54, 95% CI 0.48-0.60, P < 0.001), 36% (HR 0.64, 95% CI 0.58-0.70, P < 0.001), 31% (HR 0.69, 95% CI 0.62-0.76, P < 0.001), 25% (HR 0.75, 95% CI 0.68-0.83, P < 0.001), and 22% (HR 0.78, 95% CI 0.71-0.86, P < 0.001). In this large prospective cohort study, a higher frequency of depressive symptoms at baseline was significantly associated with increased risk of CVD in the middle-aged population, and this relationship was prominent in women. In the middle-aged population with depressive symptoms, engaging in a healthier lifestyle could prevent CVD risk.
Subject(s)
Cardiovascular Diseases , Depression , Humans , Male , Female , Adult , Middle Aged , Aged , UK Biobank , Depression/complications , Depression/epidemiology , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Life Style , Sex Factors , Prospective Studies , Cohort Studies , Heart Disease Risk FactorsABSTRACT
BACKGROUND: Computational drug repurposing is crucial for identifying candidate therapeutic medications to address the urgent need for developing treatments for newly emerging infectious diseases. The recent COVID-19 pandemic has taught us the importance of rapidly discovering candidate drugs and providing them to medical and pharmaceutical experts for further investigation. Network-based approaches can provide repurposable drugs quickly by leveraging comprehensive relationships among biological components. However, in a case of newly emerging disease, applying a repurposing methods with only pre-existing knowledge networks may prove inadequate due to the insufficiency of information flow caused by the novel nature of the disease. METHODS: We proposed a network-based complementary linkage method for drug repurposing to solve the lack of incoming new disease-specific information in knowledge networks. We simulate our method under the controlled repurposing scenario that we faced in the early stage of the COVID-19 pandemic. First, the disease-gene-drug multi-layered network was constructed as the backbone network by fusing comprehensive knowledge database. Then, complementary information for COVID-19, containing data on 18 comorbid diseases and 17 relevant proteins, was collected from publications or preprint servers as of May 2020. We estimated connections between the novel COVID-19 node and the backbone network to construct a complemented network. Network-based drug scoring for COVID-19 was performed by applying graph-based semi-supervised learning, and the resulting scores were used to validate prioritized drugs for population-scale electronic health records-based medication analyses. RESULTS: The backbone networks consisted of 591 diseases, 26,681 proteins, and 2,173 drug nodes based on pre-pandemic knowledge. After incorporating the 35 entities comprised of complemented information into the backbone network, drug scoring screened top 30 potential repurposable drugs for COVID-19. The prioritized drugs were subsequently analyzed in electronic health records obtained from patients in the Penn Medicine COVID-19 Registry as of October 2021 and 8 of these were found to be statistically associated with a COVID-19 phenotype. CONCLUSION: We found that 8 of the 30 drugs identified by graph-based scoring on complemented networks as potential candidates for COVID-19 repurposing were additionally supported by real-world patient data in follow-up analyses. These results show that our network-based complementary linkage method and drug scoring algorithm are promising strategies for identifying candidate repurposable drugs when new emerging disease outbreaks.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Pandemics , Algorithms , Proteins , Drug Repositioning/methodsABSTRACT
BACKGROUND: Hypertensive disorders during pregnancy are associated with the risk of long-term cardiovascular disease after pregnancy, but it has not yet been determined whether genetic predisposition for hypertensive disorders during pregnancy can predict the risk for long-term cardiovascular disease. OBJECTIVE: This study aimed to evaluate the risk for long-term atherosclerotic cardiovascular disease according to polygenic risk scores for hypertensive disorders during pregnancy. STUDY DESIGN: Among UK Biobank participants, we included European-descent women (n=164,575) with at least 1 live birth. Participants were divided according to genetic risk categorized by polygenic risk scores for hypertensive disorders during pregnancy (low risk, score ≤25th percentile; medium risk, score 25thâ¼75th percentile; high risk, score >75th percentile), and were evaluated for incident atherosclerotic cardiovascular disease, defined as the new occurrence of one of the following: coronary artery disease, myocardial infarction, ischemic stroke, or peripheral artery disease. RESULTS: Among the study population, 2427 (1.5%) had a history of hypertensive disorders during pregnancy, and 8942 (5.6%) developed incident atherosclerotic cardiovascular disease after enrollment. Women with high genetic risk for hypertensive disorders during pregnancy had a higher prevalence of hypertension at enrollment. After enrollment, women with high genetic risk for hypertensive disorders during pregnancy had an increased risk for incident atherosclerotic cardiovascular disease, including coronary artery disease, myocardial infarction, and peripheral artery disease, compared with those with low genetic risk, even after adjustment for history of hypertensive disorders during pregnancy. CONCLUSION: High genetic risk for hypertensive disorders during pregnancy was associated with increased risk for atherosclerotic cardiovascular disease. This study provides evidence on the informative value of polygenic risk scores for hypertensive disorders during pregnancy in prediction of long-term cardiovascular outcomes later in life.
Subject(s)
Cardiovascular Diseases , Coronary Artery Disease , Hypertension, Pregnancy-Induced , Myocardial Infarction , Peripheral Arterial Disease , Pregnancy , Humans , Female , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/genetics , Hypertension, Pregnancy-Induced/epidemiology , Hypertension, Pregnancy-Induced/genetics , Risk Factors , Myocardial Infarction/epidemiologyABSTRACT
The shared pathophysiological features of the cerebrovascular disease (CVD) and glaucoma suggest an association between the two diseases. Using the prospective UK Biobank cohort, we examined the associations between glaucoma and incident CVD and assessed the extent to which a healthy lifestyle reduced the CVD risk in subjects with glaucoma, using a scoring system consisting of four factors: current smoking, obesity, regular physical activity, and a healthy diet. During a mean follow-up time of 8.9 years, 22,649 (4.9%) incident CVD cases were documented. Multivariable Cox regression analyses revealed that subjects with glaucoma were significantly more likely to exhibit incident CVD (hazard ratio [HR]:1.19, 95% confidence interval [CI] 1.03-1.37; p = 0.016) than controls. In the further subgroup analyses, glaucoma increased incident CVD risk both in the young (40-55 years) and the old (56-70 years) and in both sexes, with higher risk in the young (HR: 1.33, CI 1.02-1.74) and female subjects (HR: 1.32, CI 1.14-1.52). When we analyze the associations between glaucoma and incident CVD by lifestyle factors, the highest absolute risks were observed in individuals with both glaucoma and an unhealthy lifestyle (HR: 2.66, CI 2.22-3.19). In conclusion, glaucoma was an independent risk factor for incident CVD. A healthy lifestyle was associated with a substantially lower risk for CVD incidence among adults with glaucoma.
Subject(s)
Cardiovascular Diseases , Glaucoma , Male , Humans , Female , Prospective Studies , Cardiovascular Diseases/etiology , Biological Specimen Banks , Life Style , Risk Factors , Incidence , Glaucoma/complications , United Kingdom/epidemiologyABSTRACT
MOTIVATION: Understanding comorbidity is essential for disease prevention, treatment and prognosis. In particular, insight into which pairs of diseases are likely or unlikely to co-occur may help elucidate the potential relationships between complex diseases. Here, we introduce the use of an inter-disease interactivity network to discover/prioritize comorbidities. Specifically, we determine disease associations by accounting for the direction of effects of genetic components shared between diseases, and categorize those associations as synergistic or antagonistic. We further develop a comorbidity scoring algorithm to predict whether diseases are more or less likely to co-occur in the presence of a given index disease. This algorithm can handle networks that incorporate relationships with opposite signs. RESULTS: We finally investigate inter-disease associations among 427 phenotypes in UK Biobank PheWAS data and predict the priority of comorbid diseases. The predicted comorbidities were verified using the UK Biobank inpatient electronic health records. Our findings demonstrate that considering the interaction of phenotype associations might be helpful in better predicting comorbidity. AVAILABILITY AND IMPLEMENTATION: The source code and data of this study are available at https://github.com/dokyoonkimlab/DiseaseInteractiveNetwork. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Algorithms , Biological Specimen Banks , Software , Comorbidity , PhenotypeABSTRACT
Objective: An internally validated, one-year risk prediction model for severe hypoglycemia (SH) in type 2 diabetes was evaluated in a general hospital setting to externally verify and validate its performance. Research design and methods: Between December 2017 to December 2019, 2,645 adult patients with type 2 diabetes who visited the diabetes center were enrolled. The receiver operating characteristics curve and Harrell C-statistics were compared to identify the discrimination of the model. The predicted and actual incidence of SH for one year in the development and validation cohorts were compared by ranking participants by deciles of predicted risk. Results: The concordance index was 0.878 in the external validation cohort. The sensitivity and specificity of the predictive model were 0.833 and 0.847, respectively. Based on the predicted risk, we stratified the groups into four categories: low (<0.05%), intermediate (0.05% to <0.5%), high (0.5% to <2.0%), and very high-risk group (≥2.0%). The actual annual incidence of SH gradually increased with the increased risk score level for the decile group (P for trend <0.001). The actual annual SH incidence significantly increased with increase in SH risk scores, which proportionately increased with age, duration of diabetes, glycated hemoglobin, and albuminuria and decreased with body mass index, renal function (p for trends <0.001 for all) in type 2 diabetes. Conclusion: On external validation, the novel one-year SH prediction model showed excellent discrimination in participants with type 2 diabetes and can effectively screen high-risk patients for SH, even in the general hospital setting.
Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemia , Adult , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/diagnosis , Hypoglycemia/epidemiology , Hypoglycemia/etiology , Incidence , Risk FactorsABSTRACT
BACKGROUND: Previous studies showed that gestational diabetes mellitus (GDM) can be a risk factor for subsequent atherosclerotic cardiovascular disease. However, there is a paucity of information regarding diverse cardiovascular outcomes in elderly women after GDM. In the current study, we examined whether women with a history of GDM have an increased risk for long-term overall cardiovascular outcomes. METHODS: Among the UK participants, we included 219,330 women aged 40 to 69 years who reported at least one live birth. The new incidence of diverse cardiovascular outcomes was compared according to GDM history by multivariable Cox proportional hazard models. In addition, causal mediation analysis was performed to examine the contribution of well-known risk factors to observed risk. RESULTS: After enrollment, 13,094 women (6.0%) developed new overall cardiovascular outcomes. Women with GDM history had an increased risk for overall cardiovascular outcomes [adjusted HR (aHR) 1.36 (95% CI 1.18-1.55)], including coronary artery disease [aHR 1.31 (1.08-1.59)], myocardial infarction [aHR 1.65 (1.27-2.15)], ischemic stroke [aHR 1.68 (1.18-2.39)], peripheral artery disease [aHR 1.69 (1.14-2.51)], heart failure [aHR 1.41 (1.06-1.87)], mitral regurgitation [aHR 2.25 (1.51-3.34)], and atrial fibrillation/flutter [aHR 1.47 (1.18-1.84)], after adjustment for age, race, BMI, smoking, early menopause, hysterectomy, prevalent disease, and medication. In mediation analysis, overt diabetes explained 23%, hypertension explained 11%, and dyslipidemia explained 10% of the association between GDM and overall cardiovascular outcome. CONCLUSIONS: GDM was associated with more diverse cardiovascular outcomes than previously considered, and conventional risk factors such as diabetes, hypertension, and dyslipidemia partially contributed to this relationship.
Subject(s)
Cardiovascular Diseases , Diabetes, Gestational , Dyslipidemias , Hypertension , Pregnancy , Female , Humans , Aged , Diabetes, Gestational/diagnosis , Diabetes, Gestational/epidemiology , Prospective Studies , Biological Specimen Banks , Risk Factors , Hypertension/epidemiology , United Kingdom/epidemiology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiologyABSTRACT
BACKGROUND: Few studies have examined the association between hypoglycemic episodes among people with type 2 diabetes (T2DM) at the time of hospitalization for heart failure (HF) and cardiovascular outcomes. METHODS: From March 2016 to June 2018, we conducted a retrospective cohort study to investigate hypoglycemia during HF hospitalization in the emergency department, three-point major adverse cardiovascular events (3P-MACE), and all-cause mortality; these were followed up through June 2021. HF hospitalization was defined according to American Heart Association criteria. Hypoglycemia was defined as a glucose level < 3.9 mmol/L at the time of HF hospitalization. We classified the enrolled patients into three groups (reference group, those without T2DM or hypoglycemia; those diagnosed with T2DM without hypoglycemia; and those with hypoglycemia and T2DM). We used Cox proportional hazard regression analysis to investigate the association between the three groups and the development of the first occurrence of 3P-MACE and all-cause mortality. RESULTS: During a median of 25 months of follow-up, a total of 783 patients admitted due to HF were analyzed. In total, 159 (20.3%) cases of 3P-MACE were identified, and the mortality rate was 20.2% (n = 158). The median age of patients was 76.0 (65.0-82.0) years, and 49.0% were men. Patients with 3P-MACE had a lower body mass index (22.6 [20.4-25.1] vs. 23.8 [21.3-26.7]), higher frequency of previous history of HF (24.5% vs. 15.7%), T2DM (64.2% vs. 47.3%), higher rates of hypoglycemia at the time of HF hospitalization (19.5% vs. 7.7%), and lower eGFR levels (61.1 [36.0-80.7] mL/min/1.73 m2 vs. 69.2 [45.8-89.5] mL/min/1.73 m2) than those without 3P-MACE. The multivariable adjusted HR of 3P-MACE was as follows: group with hypoglycemia and T2DM: HR, 2.29; 95% CI: 1.04-5.06; group with T2DM without hypoglycemia: HR: 1.42; 95% CI: 0.86-2.33; and all-cause mortality group with hypoglycemia and T2DM: HR: 2.58; 95% CI: 1.26-5.31, group with T2DM without hypoglycemia: HR: 1.32; 95% CI: 0.81-2.16; compared to the reference group (group without T2DM or hypoglycemia). CONCLUSIONS: T2DM and hypoglycemia are independent risk factors for 3P-MACE and all-cause mortality compared to those without hypoglycemia during HF hospitalization.