Diabetes & Metabolism Journal

Original Articles

COVID-19
Safety of COVID-19 Vaccines among Patients with Type 2 Diabetes Mellitus: Real-World Data Analysis: Hye Jun Kim, Sang Jun Lee, Soonok Sa, Jung Ho Bae, Gyuseon Song, Chae Won Lee, Ju Hee Kim, Sung Ryul Shim, Myunghee Hong, Hyun Wook Han; Diabetes Metab J. 2023;47(3):356-365. Published online March 6, 2023; DOI: https://doi.org/10.4093/dmj.2022.0129

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Background
Little is known about the adverse events (AEs) associated with coronavirus disease 2019 (COVID-19) vaccination in patients with type 2 diabetes mellitus (T2DM).
Methods
This study used vaccine AE reporting system data to investigate severe AEs among vaccinated patients with T2DM. A natural language processing algorithm was applied to identify people with and without diabetes. After 1:3 matching, we collected data for 6,829 patients with T2DM and 20,487 healthy controls. Multiple logistic regression analysis was used to calculate the odds ratio for severe AEs.
Results
After COVID-19 vaccination, patients with T2DM were more likely to experience eight severe AEs than controls: cerebral venous sinus thrombosis, encephalitis myelitis encephalomyelitis, Bell’s palsy, lymphadenopathy, ischemic stroke, deep vein thrombosis (DVT), thrombocytopenia (TP), and pulmonary embolism (PE). Moreover, patients with T2DM vaccinated with BNT162b2 and mRNA-1273 were more vulnerable to DVT and TP than those vaccinated with JNJ-78436735. Among patients with T2DM administered mRNA vaccines, mRNA-1273 was safer than BNT162b2 in terms of the risk of DVT and PE.
Conclusion
Careful monitoring of severe AEs in patients with T2DM may be necessary, especially for those related to thrombotic events and neurological dysfunctions after COVID-19 vaccination.

Citations

Citations to this article as recorded by

Herbal-based therapeutics for diabetic patients with SARS-Cov-2 infection
Yousef Rasmi, Ighli di Bari, Shah Faisal, Munima Haque, Pornanong Aramwit, Aline da Silva, Elmira Roshani Asl
Molecular Biology Reports.2024;[Epub] CrossRef
Tuberculosis vaccines update: Is an RNA-based vaccine feasible for tuberculosis?
Sasha E. Larsen, Susan L. Baldwin, Rhea N. Coler
International Journal of Infectious Diseases.2023; 130: S47. CrossRef
Neurological Disorders following COVID-19 Vaccination
Ying Yang, Lisu Huang
Vaccines.2023; 11(6): 1114. CrossRef
Safety of COVID-19 Vaccines among Patients with Type 2 Diabetes Mellitus: Real-World Data Analysis (Diabetes Metab J 2023;47:356-65)
Hye Jun Kim, Sung Ryul Shim, Myunghee Hong, Hyun Wook Han
Diabetes & Metabolism Journal.2023; 47(5): 717. CrossRef
Safety of COVID-19 Vaccines among Patients with Type 2 Diabetes Mellitus: Real-World Data Analysis (Diabetes Metab J 2023;47:356-65)
Jung Hun Ohn
Diabetes & Metabolism Journal.2023; 47(5): 715. CrossRef

Association of Hemoglobin A1c with Cardiovascular Disease Risk Factors and Metabolic Syndrome in Nondiabetic Adults.: Jin Hwa Kim, So Ra Choi, Jae Rok Lee, Ji Hye Shin, Sang Jun Lee, Mi Ah Han, Jong Park, Hak Yeon Bae, Sang Yong Kim; Korean Diabetes J. 2008;32(5):435-444. Published online October 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.5.435

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BACKGROUND
Glycosylated hemoglobin (HbA1c) is a useful index of mean blood glucose concentrations over the preceding 2 to 3 months. Elevated HbA1c levels (> 7%) are associated with a higher incidence of microvascular and macrovascular complications in patients with diabetes mellitus. However, the relationship between HbA1c and cardiovascualr disease risk in nondiabetic adults has been unclear. The aim of this study is to estimate the association of HbA1c with cardiovascular disease risk factors and metabolic syndrome in nondiabetic adults. METHODS: The subjects of this study included 533 adults (180 males and 353 females) aged 20~70 years (mean age: 46.9 +/- 10.12 years) without previously diagnosed diabetes who lived in Kangyang country. We examined baseline HbA1c levels and cardiovascular risk factors. Metabolic syndrome was defined based on International Diabetes Federation guidelines. RESULTS: The prevalence of metabolic syndrome significantly increased as HbA1c increased. HbA1c revealed a significant correlation with age (r = 0.258, P < 0.001), BMI (r = 0.152, P < 0.001), waist circumference (r = 0.252, P < 0.001), fasting plasma glucose (r = 0.319, P < 0.001), systolic (r = 0.100, P = 0.021), diastolic (r = 0.115, P = 0.008) blood pressure, total cholesterol (r = 0.232, P < 0.001), triglyceride (r = 0.156, P < 0.001), LDL cholesterol (r = 0.216, P < 0.001), and HDL cholesterol (r = -0.167, P < 0.001). Multiple regression analysis showed that HbA1c had a association with age, fasting plasma glucose, and dyslipidemia. The receiver operating characterstics (ROC) curve analysis determined HbA1c of 5.35% to yield optimal sensitivity and specificity corresponding to the presence of metabolic syndrome. CONCLUSION: The HbA1c level is correlated with cardiovascular risk factors and prevalence of metabolic syndrome in nondiabetic adults.

Citations

Citations to this article as recorded by

Association of Glycated Proteins with Inflammatory Proteins and Periodontal Disease Parameters
Jeneen Panezai, Mohammad Altamash, Per-Erik Engstrӧm, Anders Larsson
Journal of Diabetes Research.2020; 2020: 1. CrossRef
The Impact of Health Behaviors of Male Workers without Diabetes on HbA1c
Ji-Yun Park, Keon-Yeop Kim, Su-Jin Lee
Journal of Health Informatics and Statistics.2018; 43(4): 344. CrossRef
Impact of initial glycosylated hemoglobin level on cardiovascular outcomes in prediabetic patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention
Donghun Shin, Jinhee Ahn, Kwang Soo Cha, Jin Sup Park, Jun-Hyok Oh, Hye-Won Lee, Ju-Yong Hong, Bo-Won Kim, Taek Jong Hong
Coronary Artery Disease.2016; 27(1): 40. CrossRef
HbA1c Levels Are Associated with Chronic Kidney Disease in a Non-Diabetic Adult Population: A Nationwide Survey (KNHANES 2011–2013)
Seok Hui Kang, Da Jung Jung, Eun Woo Choi, Kyu Hyang Cho, Jong Won Park, Jun Young Do, Sheng-Nan Lu
PLOS ONE.2015; 10(12): e0145827. CrossRef
Usefulness of Glycated Hemoglobin as Diagnostic Criteria for Metabolic Syndrome
Sang Hyun Park, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee
Journal of Korean Medical Science.2012; 27(9): 1057. CrossRef
Relationship between inflammation biomarkers, antioxidant vitamins, and bone mineral density in patients with metabolic syndrome
Yesong Lee, Misung Kim, Kyungsuk Choi, Juyong Kim, Wookyung Bae, Sohye Kim, Cheongmin Sohn
Nutrition Research and Practice.2011; 5(2): 150. CrossRef

The Effect of alpha-lipoic Acid on Endothelial Dysfunction Induced by Intralipid Infusion in Healthy Volunteers.: Dong Wook Lee, Mi Jung Kim, Hye Soon Kim, Tae Sung Yun, Ho Chan Cho, Sang Jun Lee, Seung Ho Hur, Kyo Cheol Mun, Yong Won Cho, Jae Hoon Bae, In Kyu Lee; Korean Diabetes J. 2002;26(5):336-346. Published online October 1, 2002

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Abstract PDF: BACKGROUND
Endothelial dysfunciton has been proposed as an early manifestation of atherogenesis. Recently, emerging evidence suggests that hypertriglyceridemia and elevated free fatty acid are important risk factors in the development of atherosclerosis, probably through an increased oxidative stress. To clarify the hypothesis, we evaluated the effect of alpha-lipoic acid (ALA) on the endothelial dysfunction induced by intralipid infusion in healthy volunteers. METHODS: Hypertriglyceridemia and elevated free fatty acids was induced by infusion of intralipid. FMD (Flow-mediated dilation) of the brachial artery was investigated noninvasively by a high-resolution ultrasound technique in 13 young, healthy men without risk factors for coronary heart disease. RESULTS: Plasma triglyceride, free fatty acid and the superoxide anion were increased from 61.7+/-28.8 to 332.6+/-202.5 mg/dL, from 330.7+/-131.1 to 1267.0+/-486.2 microEq/L and from 6.6+/-2.2 to 8.7+/-1.5 X 10(-7)nmol/10(6)cells/30min (vs. basal p<0.001), respectively, following infusion of the intralipid. The FMD was decreased from 10.1+/-3.3 to 7.7+/-3.7% (vs. basal p<0.01) following infusion of the intralipid. After treatment with ALA, the increase in the FMD and the decrease in superoxide anion were significant. CONCLUSION: Acute hypertriglyceridemia, induced by intralipid infusion, is implicated in endothelial dysfunction. This endothelial dysfunction was reversed by treatment with ALA. These results suggest that chronic and repeated hypertriglyceridemia may play important roles in the development of atherosclerosis probably by increasing oxidative stress.

The Effect of Alpha-lipoic Acid on Endothelial Dysfunction in Postmenopausal Uncomplicated Type 2 Diabetes.: Ho Chan Cho, Sang Jun Lee, Mi Jung Kim, Hye Sun Kim, Tae Sung Yun, Sung Jae Kim, Sang Hyon Kim, Seung Ho Hur, Kyo Chul Moon, Jae Hoon Bae, In Kyu Lee; Korean Diabetes J. 2002;26(4):242-252. Published online August 1, 2002

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Abstract PDF: BACKGROUND
Recently, increased oxidative stress has been proposed as a major cause of vascular complications of patients with diabetes mellitus. Increased generation of oxygen free radicals in patients with diabetes mellitus could deplete cellular antioxidants and inactivate endothelial dependent vasodilating factor (EDRF), such as nitric oxide (NO). The purpose of this study was to evaluate whether the antioxidant alpha-lipoic acid (ALA) is effective in endothelial dysfunction of brachial artery, which induced by increased oxidative stress in postmenopausal diabetic women using high resolution ultrasound technique and initial reaction time (IRT) measurement. METHODS: We enrolled 11 menopausal women (mean age, 56.5+/-5.1 years) with uncomplicated type 2 diabetes. All patients were taking 1200 mg of ALA (Thioctacid(R), Bukwang, Korea). We measured of superoxide anion (O2-) in neutrophils as a marker of oxidative stress. Flow-mediated dilation (FMD) was measured using a high-resolution ultrasound. RESULTS: After treatment of ALA, fasting blood glucose was decreased significantly, the endothelium-dependent vasodilation of the brachial artery was increased, and O2- production was also decreased significantly. CONCLUSION: These results show that short term ALA treatment could improve the endothelial dysfunction in patients with type 2 diabetes mellitus. This improvement might be related with the antioxidants effect of ALA.

The Effect of alpha-Lipoic Acid on Vascular Smooth Muscle Cell Proliferation, Migration, Neointimal Formation and PAI-1 Expression.: Dong Woo Shin, Dong Wook Lee, Sang Jun Lee, Hye Soon Kim, Hyo Gyoung Kang, Jong Deok Ahn, In Kyu Lee; Korean Diabetes J. 2001;25(6):446-459. Published online December 1, 2001

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Abstract PDF: BACKGROUND
Exposure to large amounts of glucose causes a characteristic dysfunction and morphologic changes of the endothelium by an increased production of reactive oxygen species (ROS) in diabetes. The plasminogen activator inhibitor-1 (PAI-1), which modulates fibrinolysis and cell migration, may influence proteolysis and neointimal formation in vascular smooth muscle cells (VSMC). Antioxidants have been proposed to inhibit multiple proatherogenic events. This study investigated the effect of (alpha)-Lipoic acid on PAI-1 expression and VSMC proliferation and migration both in vivo and in vitro. METHODS: In the in vitro study, cultured rat aortic smooth muscle cells (RASMC) were incubated in a medium containing high glucose (22 mM) and 100 nM angiotensin II for 4 hour. After (alpha)-Lipoic acidtreatment, a -migration and growth assay of the RASMC, and a gel mobility shift assay and reporter gene analysis for nuclear factor- B (NF-kappa B) and northern blot analysis for PAI-1 were performed. In the in vivo study, the effect of (alpha)-Lipoic acid on neointimal hyperplasia in a rat carotid balloon injury model was evaluated. RESULTS: RASMC migration was inhibited significantly by (alpha)-Lipoic acid (p<0.01), but their proliferation was not inhibited. The NF-kappa B DNA binding activity and NF-kappa B promoter activity was inhibited by (alpha)-Lipoic acid significantly (p<0.01). (alpha)-Lipoic acid inhibited PAI-1 mRNA expression by high glucose and angiotensin II in dose dependent manner (p<0.05). In the rat carotid artery balloon injury model, neointimal formation was reduced by (alpha)-Lipoic acid treatment in a dose dependent manner significantly (p<0.01). CONCLUSION: (alpha)-Lipoic acid suppresses migration, but not proliferation in RASMC. (alpha)-Lipoic acid also reduce neointima formation in a rat carotid balloon injured model. This effect might be related to the blocking of NF-kappa B which increase the expression of the genes associated with atherosclerosis including TNF-alpha, IL-1, IL-6, endothelin-1, MCP-1, VCAM-1, ICAM-1, E-selectin, tissue factor.

The Effect of Acute Hyperglycemia on Endothelial Function in Type 2 Diabetes.: Sang Jun Lee, Dong Wook Lee, In Kyu Lee; Korean Diabetes J. 2000;24(5):574-586. Published online January 1, 2001

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Abstract: BACKGROUND
Multiple studies in patients with diabetes demonstrate impaired endothelial-dependent vasodilation. But the mechanisms of vascular dysfunction in type 2 diabetes are still controversial. Some risk factors, such as dyslipidemia, hypertension and obesity, are commonly associated with type 2 diabetes. These risk factor may cause endothelial dysfunction. And hyperglycemia may have a specific role in the increased risk of vascular complications in diabetes but it remains unclear. The purpose of this study was to examine whether endothelial dysfunction occurs when acute hyperglycemia is induced by oral glucose loading. METHOD: Using the high-resolution ultrasound, we measured flow-mediated vasodilation (endothelial dependent vasodilation: FMD) during oral glucose tolerance test in 11 men (mean age: 59+/-5 years) with type 2 diabetes without chronic diabetic complications. For statistical analysis, we used paired t-test, generalized linear method (GLM) to compare FMD before and after glucose loading. RESULT: Flow-mediated vasodilation was diminished after glucose loading (13.2+/- 6.4%, 7.3+/-3.3*%, 12.8+/-5.6%, in fasting, at 1- and 2-h, respectively; *p<0.001 vs fasting). Superoxide anion formation by neutrophils was increased after glucose loading (4.65+/-2.8, 6.17+/-2.2, in fasting, at 1-h respectively: p<0.05 vs fasting)( 10-7nmol/106cells/30min). Endothelial independent vasodilation was not significantly affected by glucose loading. The concentration of triglyceride were not changed after glucose loading. CONCLUSION: This study shows that acute hyperglycemia induced by 75 gm oral glucose intake results in endothelial dysfunction. These results suggest that prolonged and repeated hyperglycemia may play an important role in the developement and progression of vascular complication in diabetes.

An Effect of Estrogen Supplementation on the Endothelium Dependent Vasodilation in Postmenopausal Women with Type 2 Diabetes Mellitus.: Jun Kim Yeo, Sang Jun Lee, In Kyu Lee; Korean Diabetes J. 2000;24(1):37-45. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although estrogen supplementation can reduce cardiovascular events in postmenopausal women, but the mechanism that mediate this beneficial effect is unclear. Thus, we investigated the acute effect of HRT on endothelial dependent vasodilation using high resolution ultrasound in healthy and diabetic postmenopausal women. METHOD: We examined endogenous (flow dependent dilatation affer 5min cuff occlusion) and exogenous (sublingual nitroglycerin) nitric oxide mediated vasodilation in the brachial artery before and after estrogen supplementation (Premarin R 0.625 mg for 1 wk) in 16 postmenopausal women, and in 18 age-matched postmenopausal women with type 2 diabetes mellitus. RESULTS: There were no differences in age, total & LDL cholesterol level, and body mass index between the groups (p>0.05). However, HDL cholesterol level was significantly lower in patient with diabetes than in normal women (1.0+/-0.3 mmol/L in diabetes and 1.4+/-0.2 mmol/L in normal, p<0.05). Basal endothelium dependent vascular reactivity was significantly attenuated in patient with diabetes when compaired with normal subjects (8.0+/-3,9% versus 13.7+/-6.2%, p<0.05). An estrogen supplementation increased endothelium dependent vasodilation not only in patient with diabetes(from 8.0+/-3.9% to 15.1+/-4.0%, p<0.05), but also in normal women (from 13.7+/-6.2% to 20.1+/-4.7%, p<0.05). Moreover the percent increase of vascular reactivity was higher in patient with diabetes(p<0,05), In contrast, the responses to sublingual nitroglycerin were comparable in diabetes (from 21.1+/-6.0% to 22.1+/-4.1%, p>0.05), and in normal women (from 25.8+/-7.8% to 25.2+/-4.5%, p>0.05) before and after estrogen supplementation. CONCLUSION: Endothelial dysfunction was prominent in patient with diabetes and it was significantly attenuated by estrogen. These results suggest that estrogen replacement improves endothelial dependent vasodilation in healthy and diabetic postmenopausal women.

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