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Prior research has highlighted poor clinical outcomes in coronavirus disease 2019 (COVID-19)-infected patients with diabetes; however, susceptibility to COVID-19 infection in patients with diabetes has not been extensively studied. Participants aged ≥30 years who underwent COVID-19 testing from December 2019 to April 2020 were analyzed using the National Health Insurance Service data in South Korea. In a cohort comprising 29,433 1:1 propensity score-matched participants, COVID-19 positivity was significantly higher in participants with diabetes than in those without diabetes (512 [3.5%] vs. 395 [2.7%], P<0.001). Logistic regression analysis indicated that diabetes significantly increased the risk of COVID-19 test positivity (odds ratio, 1.307; 95% confidence interval, 1.144 to 1.493; P<0.001). Patients with diabetes exhibited heightened COVID-19 infection rates compared to individuals without diabetes, and diabetes increased the susceptibility to COVID-19, reinforcing the need for heightened preventive measures, particularly considering the poor clinical outcomes in this group.
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Background/Objectives: Smoking cessation is acknowledged for its health benefits. However, it paradoxically increases diabetes mellitus (DM) risk shortly after quitting due to weight gain. This research aimed to investigate how smoking status could affect the development of DM, focusing on how the risk of acquiring diabetes changed over time after quitting smoking, independent of variables such as weight gain. Methods: The data of 386,558 participants of the Kangbuk Samsung Health Study, excluding those with pre-existing DM, were examined. Smoking status and its long-term effects on DM risk were assessed using multivariate Cox proportional hazards models. Lifestyle factors, including weight change, physical activity levels, and alcohol intake, were adjusted as time-varying covariates throughout the follow-up period. Results: Modified hazard ratios (HRs) indicated no notable disparity in DM risk between individuals who previously smoked and those who had never smoked (HR: 1.04, 95% CI: 0.999-1.08, p-value < 0.001). In contrast, current smokers exhibited a significantly increased DM risk (HR: 1.29, 95% CI: 1.24-1.35, p-value < 0.001). Within the first six years post-cessation, former smokers initially faced a higher DM risk than never smokers (0-2 years, HR: 1.22, 95% CI: 1.15-1.31, p-value < 0.001; 3-5 years, HR: 1.11, 95% CI: 1.04-1.20, p-value < 0.001). After 12 years, they realigned with never smokers (12-46 years, HR: 0.92, 95% CI: 0.86-0.98, p-value = 0.002). Current smokers consistently showed a higher DM risk (0-9 years, HR: 1.29, 95% CI: 1.14-1.46, p-value < 0.001). Adjusting for covariates such as weight change and physical activity did not alter these findings. Conclusions: Our results indicated that former smokers initially experienced an elevated risk of DM relative to never smokers. This increased risk aligned with the risk of never smokers after six years, and the risk continued to improve after 12 years compared to never smokers. This contrasted with current smokers, who maintained a heightened risk of DM, even when adjustments were made for weight change, physical activity, and alcohol intake as time-varying covariates.
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BACKGRUOUND: The association between low-density lipoprotein (LDL-C) levels and cardiovascular disease (CVD) risk in different age groups within the diabetes mellitus (DM) population remains unclear. The cohort study was conducted to investigate this relationship. METHODS: We assessed the 2009 to 2012 Korean National Health Screening and National Health Insurance Service records, with follow-up to the primary outcome (myocardial infarction [MI] or stroke) or December 2018. After excluding the participants with a history of MI or stroke, 2,227,394 participants with DM were included and categorized according to baseline LDL-C levels and age. Cox proportional hazards modeling was conducted. The CVD risk of age <40 years and LDL-C <70 mg/dL was set as the reference. In each age group, LDL-C <70 mg/dL was used as a reference for the subgroup analysis. RESULTS: The cut-off LDL-C value for increased MI risk in each age group varied (<40 years old, LDL-C ≥160 mg/dL: hazard ratios [HR], 2.03; 95% confidence interval [CI], 1.644 to 2.506) (40-49-year-old, LDL-C <115 mg/dL: HR, 1.245; 95% CI, 1.04 to 1.489) (50-59-year-old, LDL-C <115 mg/dL: HR, 1.21; 95% CI, 1.014 to 1.445) (60-69-year-old, LDL-C <145 mg/dL: HR, 1.229; 95% CI, 1.022 to 1.479) (≥70 years old group, LDL-C <100 mg/dL: HR, 1.238; 95% CI, 1.018 to 1.504). The cut-off LDL-C values for increased stroke risk varied in each age subgroup (<40 years old, LDL-C ≥160 mg/dL: HR, 1.395; 95% CI, 1.094 to 1.779) (40-49-year-old, LDL-C <145 mg/dL: HR, 1.13; 95% CI, 1.019 to 1.253) (50-59-year-old, LDL-C <160 mg/dL: HR, 1.079; 95% CI, 1.008 to 1.154) (60-69-year-old, LDL-C <130 mg/dL: HR, 1.07; 95% CI, 1.022 to 1.119) (≥70 years old, LDL-C <115 mg/dL: HR, 1.064; 95% CI, 1.019 to 1.112). CONCLUSION: The effect of LDL-C on the risk of CVD differs depending on the age of the population with DM.
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Doenças Cardiovasculares , Diabetes Mellitus , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Adulto , Idoso , Pessoa de Meia-Idade , Estudos de Coortes , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol , Infarto do Miocárdio/epidemiologia , Diabetes Mellitus/epidemiologia , Acidente Vascular Cerebral/epidemiologia , República da Coreia/epidemiologiaRESUMO
BACKGRUOUND: Polyunsaturated fatty acids (PUFAs) reportedly have protective effects on pancreatic ß-cells; however, the underlying mechanisms are unknown. METHODS: To investigate the cellular mechanism of PUFA-induced cell protection, mouse insulinoma 6 (MIN6) cells were cultured with palmitic acid (PA) and/or docosahexaenoic acid (DHA), and alterations in cellular signaling and apoptosis were examined. RESULTS: DHA treatment remarkably repressed caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL)-positive red dot signals in PA-treated MIN6 cells, with upregulation of autophagy, an increase in microtubule- associated protein 1-light chain 3 (LC3)-II, autophagy-related 5 (Atg5), and decreased p62. Upstream factors involved in autophagy regulation (Beclin-1, unc51 like autophagy activating kinase 1 [ULK1], phosphorylated mammalian target of rapamycin [mTOR], and protein kinase B) were also altered by DHA treatment. DHA specifically induced phosphorylation on S2448 in mTOR; however, phosphorylation on S2481 decreased. The role of G protein-coupled receptor 120 (GPR120) in the effect of DHA was demonstrated using a GPR120 agonist and antagonist. Additional treatment with AH7614, a GPR120 antagonist, significantly attenuated DHA-induced autophagy and protection. Taken together, DHA-induced autophagy activation with protection against PA-induced apoptosis mediated by the GPR120/mTOR axis. CONCLUSION: These findings indicate that DHA has therapeutic effects on PA-induced pancreatic ß-cells, and that the cellular mechanism of ß-cell protection by DHA may be a new research target with potential pharmacotherapeutic implications in ß-cell protection.
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Autofagia , Ácidos Docosa-Hexaenoicos , Células Secretoras de Insulina , Transdução de Sinais , Animais , Camundongos , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Palmitatos/farmacologia , Ácido Palmítico/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGRUOUND: Inconsistent results have been reported regarding the association between the use of antidiabetic drugs and the clinical outcomes of coronavirus disease 2019 (COVID-19). This study aimed to investigate the effect of antidiabetic drugs on COVID-19 outcomes in patients with diabetes using data from the National Health Insurance Service (NHIS) in South Korea. METHODS: We analyzed the NHIS data of patients aged ≥20 years who tested positive for COVID-19 and were taking antidiabetic drugs between December 2019 and June 2020. Multiple logistic regression analysis was performed to analyze the clinical outcomes of COVID-19 based on the use of antidiabetic drugs. RESULTS: A total of 556 patients taking antidiabetic drugs tested positive for COVID-19, including 271 male (48.7%), most of whom were in their sixties. Of all patients, 433 (77.9%) were hospitalized, 119 (21.4%) received oxygen treatment, 87 (15.6%) were admitted to the intensive care unit, 31 (5.6%) required mechanical ventilation, and 61 (11.0%) died. Metformin was significantly associated with the lower risks of mechanical ventilation (odds ratio [OR], 0.281; 95% confidence interval [CI], 0.109 to 0.720; P=0.008), and death (OR, 0.395; 95% CI, 0.182 to 0.854; P=0.018). Dipeptidylpeptidase-4 inhibitor (DPP-4i) were significantly associated with the lower risks of oxygen treatment (OR, 0.565; 95% CI, 0.356 to 0.895; P=0.015) and death (OR, 0.454; 95% CI, 0.217 to 0.949; P=0.036). Sulfonylurea was significantly associated with the higher risk of mechanical ventilation (OR, 2.579; 95% CI, 1.004 to 6.626; P=0.049). CONCLUSION: In patients with diabetes and COVID-19, metformin exhibited reduced risks of mechanical ventilation and death, DPP- 4i was linked with lower risks of oxygen treatment and death, while sulfonylurea was related to the increased risk of mechanical ventilation.
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COVID-19 , Hipoglicemiantes , Humanos , Masculino , Hipoglicemiantes/uso terapêutico , Feminino , Pessoa de Meia-Idade , COVID-19/epidemiologia , COVID-19/mortalidade , República da Coreia/epidemiologia , Idoso , Adulto , Respiração Artificial/estatística & dados numéricos , SARS-CoV-2 , Metformina/uso terapêutico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/tratamento farmacológico , Tratamento Farmacológico da COVID-19 , Hospitalização/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem , Inibidores da Dipeptidil Peptidase IV/uso terapêuticoRESUMO
BACKGRUOUND: Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states. METHODS: Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco's modified Eagle's medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours. RESULTS: SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation. CONCLUSION: These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.
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Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Gluconeogênese/genética , Glucose , Fosfoenolpiruvato Carboxiquinase (ATP)/genética , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Proteínas Proto-Oncogênicas c-akt/uso terapêutico , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/farmacologia , Transdução de Sinais , Sódio/metabolismo , Sódio/farmacologia , Sódio/uso terapêutico , Transportador 2 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/farmacologia , Transportador 2 de Glucose-Sódio/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
BACKGRUOUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA), which is a therapeutic agent for the treatment of type 2 diabetes mellitus, has a beneficial effect on the cardiovascular system. METHODS: To examine the protective effects of GLP-1RAs on proliferation and migration of vascular smooth muscle cells (VSMCs), A-10 cells exposed to angiotensin II (Ang II) were treated with either exendin-4, liraglutide, or dulaglutide. To examine the effects of GLP-1RAs on vascular calcification, cells exposed to high concentration of inorganic phosphate (Pi) were treated with exendin-4, liraglutide, or dulaglutide. RESULTS: Ang II increased proliferation and migration of VSMCs, gene expression levels of Ang II receptors AT1 and AT2, proliferation marker of proliferation Ki-67 (Mki-67), proliferating cell nuclear antigen (Pcna), and cyclin D1 (Ccnd1), and the protein expression levels of phospho-extracellular signal-regulated kinase (p-Erk), phospho-c-JUN N-terminal kinase (p-JNK), and phospho-phosphatidylinositol 3-kinase (p-Pi3k). Exendin-4, liraglutide, and dulaglutide significantly decreased the proliferation and migration of VSMCs, the gene expression levels of Pcna, and the protein expression levels of p-Erk and p-JNK in the Ang II-treated VSMCs. Erk inhibitor PD98059 and JNK inhibitor SP600125 decreased the protein expression levels of Pcna and Ccnd1 and proliferation of VSMCs. Inhibition of GLP-1R by siRNA reversed the reduction of the protein expression levels of p-Erk and p-JNK by exendin-4, liraglutide, and dulaglutide in the Ang II-treated VSMCs. Moreover, GLP-1 (9-36) amide also decreased the proliferation and migration of the Ang II-treated VSMCs. In addition, these GLP-1RAs decreased calcium deposition by inhibiting activating transcription factor 4 (Atf4) in Pi-treated VSMCs. CONCLUSION: These data show that GLP-1RAs ameliorate aberrant proliferation and migration in VSMCs through both GLP-1Rdependent and independent pathways and inhibit Pi-induced vascular calcification.
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Diabetes Mellitus Tipo 2 , Calcificação Vascular , Humanos , Angiotensina II/farmacologia , Angiotensina II/metabolismo , Exenatida/farmacologia , Liraglutida/farmacologia , Músculo Liso Vascular/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Antígeno Nuclear de Célula em Proliferação/farmacologia , Receptores de Peptídeos Semelhantes ao Glucagon , Diabetes Mellitus Tipo 2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Fosfatos/metabolismo , Fosfatos/farmacologia , Proliferação de Células , Calcificação Vascular/metabolismoRESUMO
Background: We aimed to compare efficacy and safety between gemigliptin add-on and escalation of the metformin dose in patients with inadequately controlled type 2 diabetes mellitus (T2DM) despite treatment with metformin and SGLT2 inhibitors. Methods: This study was a multicenter, randomized, open-label, active-controlled, parallel-group comparative study. Patients with T2DM uncontrolled on metformin and SGLT2 inhibitors were randomized to receive gemigliptin 50 mg as an add-on (GEM group, n = 37) or escalation of the metformin dose (500 mg, MET group, n = 38) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to week 24. Results: At weeks 12 and 24, the reduction in HbA1c levels was significantly greater in the GEM group than in the MET group (GEM vs. MET = -0.64% ± 0.34% vs. -0.36% ± 0.50%, p = 0.009 at week 12; -0.61% ± 0.35% vs. -0.33% ± 0.70%, p = 0.045 at week 24). The proportions of patients who achieved target HbA1c levels of <7.0% at weeks 12 and 24 and <6.5% at week 12 were greater in the GEM group than in the MET group. An index of ß-cell function was also significantly improved in the GEM group. The safety profiles were similar between the two groups. Conclusions: Gemigliptin add-on therapy may be more effective than metformin dose escalation in patients with T2DM insufficiently controlled using metformin and SGLT2 inhibitors, without safety concerns. This trial is registered with CRIS_number: KCT0003520.
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Diabetes Mellitus Tipo 2 , Metformina , Piperidonas , Pirimidinas , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Hemoglobinas Glicadas , Controle Glicêmico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Resultado do TratamentoRESUMO
BACKGRUOUND: Recent diabetes management guidelines recommend that sodium-glucose cotransporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1RAs) with proven cardiovascular benefits should be prioritized for combination therapy in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD). This study was aimed at evaluating SGLT2i or GLP-1RA usage rates and various related factors in patients with T2DM and established CVD. METHODS: We enrolled adults with T2DM aged ≥30 years who were hospitalized due to established CVD from January 2019 to May 2020 at 13 secondary and tertiary hospitals in Korea in this retrospective observational study. RESULTS: Overall, 2,050 patients were eligible for analysis among 2,107 enrolled patients. The mean patient age, diabetes duration, and glycosylated hemoglobin level were 70.0 years, 12.0 years, and 7.5%, respectively. During the mean follow-up duration of 9.7 months, 25.7% of the patients were prescribed SGLT2is after CVD events. However, only 1.8% were prescribed GLP-1RAs. Compared with SGLT2i non-users, SGLT2i users were more frequently male and obese. Furthermore, they had a shorter diabetes duration but showed worse glycemic control and better renal function at the time of the event. GLP-1RA users had a longer duration of diabetes and worse glycemic control at the time of the event than GLP-1RA non-users. CONCLUSION: The SGLT2i or GLP-1RA prescription rates were suboptimal in patients with T2DM and established CVD. Sex, body mass index, diabetes duration, glycemic control, and renal function were associated with the use of these agents.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Adulto , Humanos , Masculino , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemiantes/farmacologia , Estudos Retrospectivos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , República da Coreia/epidemiologiaRESUMO
BACKGROUND: The risk of heart failure (HF) in underweight diabetes mellitus (DM) patients has rarely been studied. We conducted a cohort study to investigate the association between underweight (BMI < 18.5 kg/m2) and BMI change over time and the risk of HF in patients with type 2 DM. METHODS: We utilized the health screening data from the National Health Insurance Service and the Korean National Health Screening database from 2009 to 2012, with follow-up until December 2018. Participants with DM were categorized into four groups based on their BMI at 4 years before study inclusion and BMI at the study entry: (1) Always Normal Weight (BMI at 4 years ago/BMI at study entry ≥18.5/≥18.5 kg/m2, reference group); (2) Transitioned to Underweight (≥18.5/<18.5 kg/m2); (3) Transitioned to Normal Weight (<18.5/≥18.5 kg/m2) and (4) Always Underweight (<18.5/<18.5 kg/m2). Participants were followed until the development of HF or at the end of the follow-up. Initial screening data included participants with DM who had the health screening during the study period (n = 2,746,079). Participants aged <20 years (n = 390), those who did not undergo health examination 4 years prior (n = 1,306,520), and those with missing data (n = 77,410) were excluded. Participants diagnosed with HF before study participation (n = 81,645) and within 1 year of study enrolment (n = 11,731) were excluded. After applying exclusion criteria, 1,268,383 participants were finally included in the analysis. The primary outcome was the development of HF. We employed Cox proportional hazards models, adjusting for various confounding factors, to assess the risk of developing HF. RESULTS: Median follow-up duration was 6.88 years and men were 63.16%. The mean ages of each groups were as follows: Always Normal Weight (57.92 ± 11.64 years), Transitioned to Underweight (62 ± 13.5 years), Transitioned to Normal Weight (56.6 ± 15.29 years) and Always Underweight (57.76 ± 15.35 years). In comparison with the Always Normal Weight group (n = 1,245,381, HF = 76,360), Transitioned to Underweight group (≥18.5/<18.5 kg/m2, n = 9304, HF = 880, adjusted Hazard Ratio (aHR)1.389, 95% confidence interval (CI) 1.3-1.485) or Transitioned to Normal Weight (<18.5/≥18.5 kg/m2, n = 6024, HF = 478, aHR 1.385, 95% CI 1.266-1.515) exhibited an increased risk of HF. The highest risk was observed in the Always Underweight group (<18.5/<18.5 kg/m2, n = 7674, HF = 665, aHR 1.612, 95% CI 1.493-1.740). CONCLUSIONS: Underweight was significantly associated with the risk of HF in the DM population. Active surveillance for HF in an underweight DM population is needed.
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Diabetes Mellitus , Insuficiência Cardíaca , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Estudos de Coortes , Obesidade/complicações , Magreza/complicações , Magreza/epidemiologia , Fatores de Risco , Índice de Massa Corporal , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/complicações , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologiaRESUMO
CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Obesity and metabolic syndrome are known risk factors for thyroid cancer. OBJECTIVE: We investigated the association between NAFLD and thyroid cancer risk in young adults. METHODS: This nationwide cohort study included 1 135 967 participants aged 20 to 39 years who underwent 4 consecutive health screenings in South Korea. NAFLD was categorized using the fatty liver index (FLI), as follows: ≥60, 30 to 60, and <30. The cumulative FLI points were defined as the number of times participants had a FLI of ≥30 (0-4). RESULTS: During a median follow-up of 5.2 years, 4126 participants (0.36%) were newly diagnosed with thyroid cancer. Compared with the participants with an FLI of <30, those with an FLI of 30 to 60 (men: hazard ratio [HR] 1.36 [95% CI, 1.22-1.51] and women: HR 1.44 [1.21-1.70]) and those with an FLI of ≥60 (men: HR 1.71 [1.53-1.92] and women: HR 1.81 [1.46-2.25]) had a significantly higher risk of thyroid cancer. Participants with higher cumulative FLI points had a higher risk of thyroid cancer compared to those with a cumulative FLI point of 0 (P < .001). During the follow-up period, the participants with an increased FLI exhibited an increased risk of thyroid cancer. CONCLUSION: NAFLD was associated with an increased risk of thyroid cancer in young adults. Repeatedly elevated FLI and progression of NAFLD were associated with an increased risk of thyroid cancer in this study.
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Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Neoplasias da Glândula Tireoide , Masculino , Humanos , Feminino , Adulto Jovem , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Síndrome Metabólica/complicações , Estudos de Coortes , Fatores de Risco , Neoplasias da Glândula Tireoide/etiologia , Neoplasias da Glândula Tireoide/complicaçõesRESUMO
BACKGRUOUND: The effect of obesity on the development of type 2 diabetes mellitus (DM) in different age groups remains unclear. We assessed the impact of obesity on the development of DM for two age groups (40-year-old, middle age; 66-year-old, older adults) in the Korean population. METHODS: We analyzed Korean National Health Insurance Service data of 4,145,321 Korean adults with 40- and 66-year-old age without DM, between 2009 and 2014. Participants were followed up until 2017 or until the diagnosis of DM. We assessed the risk of DM based on the body mass index and waist circumference of the participants. Multiple confounding factors were adjusted. RESULTS: The median follow-up duration was 5.6 years. The association of general and abdominal obesity with the risk of DM development was stronger in the 40-year-old group (general obesity: hazard ratio [HR], 3.566, 95% confidence interval [CI], 3.512 to 3.622; abdominal obesity: HR, 3.231; 95% CI, 3.184 to 3.278) than in the 66-year-old group (general obesity: HR, 1.739; 95% CI, 1.719 to 1.759; abdominal obesity: HR, 1.799; 95% CI, 1.778 to 1.820). In the 66-year-old group, abdominal obesity had a stronger association with the development of DM as compared to general obesity. In the 40-year-old group, general obesity had a stronger association with the risk of DM development than abdominal obesity. CONCLUSION: The influence of general and abdominal obesity on the development of DM differed according to age. In older adults, abdominal obesity had a stronger association with DM development than general obesity.
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Diabetes Mellitus Tipo 2 , Pessoa de Meia-Idade , Humanos , Idoso , Adulto , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Fatores de Risco , Obesidade/complicações , Obesidade/epidemiologia , Índice de Massa CorporalRESUMO
BACKGRUOUND: Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden. METHODS: We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease. RESULTS: The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100. CONCLUSION: CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.
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Doenças Cardiovasculares , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Calcificação Vascular , Humanos , Diabetes Mellitus Tipo 2/complicações , Doenças Cardiovasculares/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Cálcio , Estudos de Coortes , Angiografia Coronária/métodos , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Medição de Risco/métodosRESUMO
AIMS: Physical inactivity is a modifiable risk factor for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM); however, little is known about its association with mortality due to other causes. Herein, we investigated the association between physical activity (PA) and cause-specific mortality in patients with T2DM. METHODS: We analyzed data from the Korean National Health Insurance Service and claims database of adults with T2DM aged >20 years at baseline (n = 2,651,214). Each participant's PA volume was measured as the metabolic equivalent of tasks (METs)-min per week, and hazard ratios of all-cause and cause-specific mortality relative to PA levels were estimated. RESULTS: During the 7.8 years of follow-up, all-cause, CVD, respiratory, cancer, and other causes of mortality were lowest in patients engaged in vigorous PA. MET-min/week was inversely associated with mortality after adjusting for covariates. The reduction in total and cause-specific mortality was greater in patients aged ≥65 years than in those aged <65 years. CONCLUSIONS: Increasing PA may facilitate a reduction in mortality from various causes, especially among older patients with T2DM. Clinicians should encourage such patients to increase their daily PA levels to reduce their risk of mortality.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicações , Estudos de Coortes , Causas de Morte , Exercício Físico , Fatores de Risco , Doenças Cardiovasculares/etiologiaRESUMO
BACKGROUND: Few studies have assessed the correlation between coexisting mental disorders in participants with diabetes mellitus (DM) and the risk of heart failure (HF). Herein, we conducted a cohort study to determine the association between the accumulation of mental disorders in participants with DM and the risk of HF. METHODS: The Korean National Health Insurance Service records were assessed. 2,447,386 adults with DM who underwent health screening between 2009 and 2012 were analyzed. Participants with major depressive disorder, bipolar disorder, schizophrenia, insomnia, or anxiety disorders were included. In addition, participants were categorized based on the number of coexisting mental disorders. Each participant was followed until December 2018 or until the onset of HF. Cox proportional hazard modelling with confounding factors adjustment was conducted. In addition, a competing risk analysis was conducted. Subgroup analysis assessed the impact of clinical variables on the association between the accumulation of mental disorders and the risk of HF. RESULTS: The median follow-up duration was 7.09 years. The accumulation of mental disorders was associated with a risk of HF (zero mental disorder (0), reference; 1 mental disorder, adjusted hazard ratio (aHR): 1.222, 95% confidence intervals (CI): 1.207-1.237; 2 mental disorders, aHR: 1.426, CI: 1.403-1.448; ≥3 mental disorders, aHR: 1.667, CI: 1.632-1.70. In the subgroup analysis, the strength of association was the strongest in the younger age group (< 40 years, 1 mental disorder, aHR 1.301, CI 1.143-1.481; ≥2 mental disorders, aHR 2.683, CI 2.257-3.190; 40-64 years, 1 mental disorder, aHR 1.289, CI 1.265-1.314; ≥2 mental disorders, aHR 1.762, CI 1.724-1.801; ≥65 years, 1 mental disorder, aHR 1.164, CI 1.145-1.183; ≥2 mental disorders, aHR 1.353, CI 1.330-1.377; Pinter<0.001). In addition, income, BMI, hypertension, chronic kidney disease, history of cardiovascular disease, insulin use, and duration of DM showed significant interactions. CONCLUSIONS: Comorbid mental disorders in participants with DM are associated with an increased risk of HF. In addition, the association was stronger in a younger age group. Participants with DM and mental disorders should be monitored with increased frequency for signs of HF; for which they have a higher risk than the general population.
Assuntos
Transtorno Depressivo Maior , Diabetes Mellitus , Insuficiência Cardíaca , Transtornos Mentais , Adulto , Humanos , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
Diabetes Technology Society assembled a panel of clinician experts in diabetology, cardiology, clinical chemistry, nephrology, and primary care to review the current evidence on biomarker screening of people with diabetes (PWD) for heart failure (HF), who are, by definition, at risk for HF (Stage A HF). This consensus report reviews features of HF in PWD from the perspectives of 1) epidemiology, 2) classification of stages, 3) pathophysiology, 4) biomarkers for diagnosing, 5) biomarker assays, 6) diagnostic accuracy of biomarkers, 7) benefits of biomarker screening, 8) consensus recommendations for biomarker screening, 9) stratification of Stage B HF, 10) echocardiographic screening, 11) management of Stage A and Stage B HF, and 12) future directions. The Diabetes Technology Society panel recommends 1) biomarker screening with one of two circulating natriuretic peptides (B-type natriuretic peptide or N-terminal prohormone of B-type natriuretic peptide), 2) beginning screening five years following diagnosis of type 1 diabetes (T1D) and at the diagnosis of type 2 diabetes (T2D), 3) beginning routine screening no earlier than at age 30 years for T1D (irrespective of age of diagnosis) and at any age for T2D, 4) screening annually, and 5) testing any time of day. The panel also recommends that an abnormal biomarker test defines asymptomatic preclinical HF (Stage B HF). This diagnosis requires follow-up using transthoracic echocardiography for classification into one of four subcategories of Stage B HF, corresponding to risk of progression to symptomatic clinical HF (Stage C HF). These recommendations will allow identification and management of Stage A and Stage B HF in PWD to prevent progression to Stage C HF or advanced HF (Stage D HF).
Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Humanos , Adulto , Peptídeo Natriurético Encefálico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Consenso , Biomarcadores , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/epidemiologiaRESUMO
In this national cohort study, the patients with acromegaly had significantly higher risks of clinical vertebral (HR 2.09 [1.58-2.78]) and hip (HR 2.52 [1.61-3.95]) fractures than the controls. The increased fracture risk in patients with acromegaly was time-dependent and was observed even during the early period of follow-up. PURPOSE: Acromegaly is characterized by the overproduction of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), both play important roles in regulating bone metabolism. We investigated the risk of vertebral and hip fractures in patients with acromegaly compared to age- and sex-matched controls. METHODS: This nationwide population-based cohort study included 1,777 patients with acromegaly aged 40 years or older in 2006-2016 and 8,885 age- and sex-matched controls. A Cox proportional hazards model was used to estimate the adjusted hazard ratio (HR) [95% confidence interval]. RESULTS: The mean age was 54.3 years and 58.9% were female. For approximately 8.5 years of follow-up, the patients with acromegaly had significantly higher risks of clinical vertebral (HR 2.09 [1.58-2.78]) and hip (HR 2.52 [1.61-3.95]) fractures than the controls in the multivariate analyses. There were significant differences in the risks of clinical vertebral (P < 0.0001) and hip (P < 0.0001) fractures between the patients with acromegaly and the controls in the Kaplan-Meier survival analysis. The multivariable-adjusted HRs for clinical vertebral fractures comparing the patients with acromegaly with controls during and excluding the first 7 years of observation were 1.69 [1.15-2.49] and 2.70 [1.75-4.17], respectively. The HRs for hip fractures during and excluding the first 7 years of observation were 2.29 [1.25-4.18] and 3.36 [1.63-6.92], respectively. CONCLUSIONS: The patients with acromegaly had a higher risk of hip fractures as well as clinical vertebral fractures than the controls. The increased fracture risk in patients with acromegaly was time-dependent and was observed even during the early period of follow-up.
Assuntos
Acromegalia , Fraturas do Quadril , Fraturas da Coluna Vertebral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acromegalia/complicações , Estudos de Coortes , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Coluna Vertebral , AdultoRESUMO
BACKGROUND: Although diabetes is a risk factor for atrial fibrillation (AF), studies on the AF risk according to the antidiabetic drugs are lacking. This study evaluated the effects of antidiabetic drugs on AF incidence in Korean patients with type 2 diabetes. METHODS: We included 2,515,468 patients with type 2 diabetes from the Korean National Insurance Service database without a history of AF who underwent health check-ups between 2009 and 2012. Newly diagnosed AF incidence was recorded until December 2018 according to the main antidiabetic drug combinations used in the real world. RESULTS: Of the patients included (mean age, 62 ± 11 years; 60 % men), 89,125 were newly diagnosed with AF. Metformin (MET) alone (hazard ratio [HR] 0.959, 95 % CI 0.935-0.985) and MET combination therapy (HR < 1) significantly decreased the risk of AF compared to the no-medication group. The antidiabetic drugs consistently showing a protective effect against AF incidence were MET (HR 0.977, 95 % CI 0.964-0.99) and thiazolidinedione (TZD; HR 0.926, 95 % CI 0.898-0.956), even after adjusting for various factors. Moreover, this protective effect was more remarkable with MET and TZD combination therapy (HR 0.802, 95 % CI 0.754-0.853) than with other drug combinations. In the subgroup analysis, the preventive effect of MET and TZD treatment against AF remained consistent, regardless of age, sex, duration, and diabetes severity. CONCLUSION: The combination therapy of MET and TZD is the most effective antidiabetic drug for preventing AF in patients with type 2 diabetes.
Assuntos
Fibrilação Atrial , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Metformina , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemiantes/uso terapêutico , Incidência , Metformina/uso terapêutico , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: There are no clear data to support the cardiovascular (CV) risk categories and low-density lipoprotein cholesterol (LDL-C) treatment goals in Korean people with type 2 diabetes mellitus (T2DM). We evaluated the incidence of cardiovascular disease (CVD) according to comorbidities and suggested LDL-C treatment goals in Korean people with T2DM in nationwide cohort data. METHODS: Using the Korean National Health Insurance Service database, 248,002 people aged 30 to 90 years with T2DM who underwent routine health check-ups during 2009 were included. Subjects with previous CVD were excluded from the study. The primary outcome was incident CVD, defined as a composite of myocardial infarction and ischemic stroke during the follow-up period from 2009 to 2018. RESULTS: The mean age of the study participants was 59.6±10.9 years, and median follow-up period was 9.3 years. CVD incidence increased in the order of DM duration of 5 years or more (12.04/1,000 person-years), hypertension (HT) (12.27/1,000 personyears), three or more CV risk factors (14.10/1,000 person-years), and chronic kidney disease (18.28/1,000 person-years). The risk of incident CVD increased linearly from an LDL-C level of ≥70 mg/dL in most patients with T2DM. In T2DM patients without HT or with a DM duration of less than 5 years, the CVD incidence increased from LDL-C level of ≥100 mg/dL. CONCLUSION: For primary prevention of CVD in Korean adults with T2DM, it can be helpful to lower LDL-C targets when there are chronic kidney disease, HT, a long duration of diabetes mellitus, or three or more CV risk factors.