Diabetes & Metabolism Journal

Original Article

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Comparison of Vildagliptin and Pioglitazone in Korean Patients with Type 2 Diabetes Inadequately Controlled with Metformin: Jong Ho Kim, Sang Soo Kim, Hong Sun Baek, In Kyu Lee, Dong Jin Chung, Ho Sang Sohn, Hak Yeon Bae, Mi Kyung Kim, Jeong Hyun Park, Young Sik Choi, Young Il Kim, Jong Ryeal Hahm, Chang Won Lee, Sung Rae Jo, Mi Kyung Park, Kwang Jae Lee, In Joo Kim; Diabetes Metab J. 2016;40(3):230-239. Published online April 5, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.3.230

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Background

We compared the efficacies of vildagliptin (50 mg twice daily) relative to pioglitazone (15 mg once daily) as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c) levels in Korean patients with type 2 diabetes.

Methods

The present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin.

Results

The mean changes in HbA1c levels from baseline were –0.94% in the vildagliptin group and –0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG) levels were –60.2 mg/dL in the vildagliptin group and –38.2 mg/dL in the pioglitazone group and these values significantly differed (P=0.040). There were significant decreases in the levels of total, low density lipoprotein, high density lipoprotein (HDL), and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group. The mean change in body weight was –0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group, which were also significantly different (P=0.002).

Conclusion

As an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.

Citations

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Factors contributing to the adverse drug reactions associated with the dipeptidyl peptidase-4 (DPP-4) inhibitors: A scoping review
Swetha R. Reghunath, Muhammed Rashid, Viji Pulikkel Chandran, Girish Thunga, K.N. Shivashankar, Leelavathi D. Acharya
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(7): 102790. CrossRef
Efficacy and safety of evogliptin in patients with type 2 diabetes and non‐alcoholic fatty liver disease: A multicentre, double‐blind, randomized, comparative trial
Eugene Han, Ji Hye Huh, Eun Y. Lee, Ji C. Bae, Sung W. Chun, Sung H. Yu, Soo H. Kwak, Kyong S. Park, Byung‐Wan Lee
Diabetes, Obesity and Metabolism.2022; 24(4): 752. CrossRef
A double‐blind, Randomized controlled trial on glucose‐lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase‐4 inhibitor therapy: REFIND study
Soree Ryang, Sang Soo Kim, Ji Cheol Bae, Ji Min Han, Su Kyoung Kwon, Young Il Kim, Il Seong Nam‐Goong, Eun Sook Kim, Mi‐kyung Kim, Chang Won Lee, Soyeon Yoo, Gwanpyo Koh, Min Jeong Kwon, Jeong Hyun Park, In Joo Kim
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The rs12617336 and rs17574 Dipeptidyl Peptidase-4 Polymorphisms Are Associated With Hypoalphalipoproteinemia and Dipeptidyl Peptidase-4 Serum Levels: A Case-Control Study of the Genetics of Atherosclerotic Disease (GEA) Cohort
Gilberto Vargas-Alarcón, María del Carmen González-Salazar, Christian Vázquez-Vázquez, Adrián Hernández-Díaz Couder, Fausto Sánchez-Muñoz, Juan Reyes-Barrera, Sergio A. Criales-Vera, Marco Sánchez-Guerra, Citlalli Osorio-Yáñez, Rosalinda Posadas-Sánchez
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Combination Therapy of Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus
Min Kyong Moon
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Comparative Cardiovascular Risks of Dipeptidyl Peptidase-4 Inhibitors: Analyses of Real-world Data in Korea
Kyoung Hwa Ha, Bongseong Kim, Hae Sol Shin, Jinhee Lee, Hansol Choi, Hyeon Chang Kim, Dae Jung Kim
Korean Circulation Journal.2018; 48(5): 395. CrossRef
Safety and efficacy of low dose pioglitazone compared with standard dose pioglitazone in type 2 diabetes with chronic kidney disease: A randomized controlled trial
Bancha Satirapoj, Khanin Watanakijthavonkul, Ouppatham Supasyndh, Stephen L Atkin
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Combination therapy of oral hypoglycemic agents in patients with type 2 diabetes mellitus
Min Kyong Moon, Kyu Yeon Hur, Seung-Hyun Ko, Seok-O Park, Byung-Wan Lee, Jin Hwa Kim, Sang Youl Rhee, Hyun Jin Kim, Kyung Mook Choi, Nan-Hee Kim
The Korean Journal of Internal Medicine.2017; 32(6): 974. CrossRef
Combination Therapy of Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus
Min Kyong Moon, Kyu-Yeon Hur, Seung-Hyun Ko, Seok-O Park, Byung-Wan Lee, Jin Hwa Kim, Sang Youl Rhee, Hyun Jin Kim, Kyung Mook Choi, Nan-Hee Kim
Diabetes & Metabolism Journal.2017; 41(5): 357. CrossRef
Efficacy and safety of adding evogliptin versus sitagliptin for metformin‐treated patients with type 2 diabetes: A 24‐week randomized, controlled trial with open label extension
Sang‐Mo Hong, Cheol‐Young Park, Dong‐Min Hwang, Kyung Ah Han, Chang Beom Lee, Choon Hee Chung, Kun‐Ho Yoon, Ji‐Oh Mok, Kyong Soo Park, Sung‐Woo Park
Diabetes, Obesity and Metabolism.2017; 19(5): 654. CrossRef
Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
The Korean Journal of Internal Medicine.2017; 32(6): 947. CrossRef
Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
Diabetes & Metabolism Journal.2017; 41(5): 337. CrossRef

Response

Response: Clinical Marker of Platelet Hyperreactivity in Diabetes Mellitus (Diabetes Metab J 2013;37:423-8): Jin Hwa Kim, Hak Yeon Bae, Sang Yong Kim; Diabetes Metab J. 2014;38(2):160-161. Published online April 18, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.2.160

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Impact of Uncontrolled Diabetes Mellitus on Blood Cells Indices and Plasma Components in Patients Without Nephropathy
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Bioscience Reports.2019;[Epub] CrossRef
The relationship between mean platelet volume and diabetic retinopathy: a systematic review and meta-analysis
ShuaiFei Ji, Jie Zhang, XiuDe Fan, XiQiang Wang, XiaoNa Ning, BaBo Zhang, Heng Shi, Hong Yan
Diabetology & Metabolic Syndrome.2019;[Epub] CrossRef
Platelets volume indexes and cardiovascular risk factors
Thaís Resende Batista, Roberta Carvalho de Figueiredo, Danyelle Romana Alves Rios
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Review

Clinical Marker of Platelet Hyperreactivity in Diabetes Mellitus: Jin Hwa Kim, Hak Yeon Bae, Sang Yong Kim; Diabetes Metab J. 2013;37(6):423-428. Published online December 12, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.6.423

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Abstract PDF PubReader

Atherothrombotic complications are important causes of morbidity and mortality in diabetic patients. Diabetes has been considered to be a prothrombotic status. Several factors contribute to the prothrombotic condition, such as increasing coagulation, impaired fibrinolysis, endothelial dysfunction, and platelet hyperreactivity. Among the factors that contribute to the prothrombotic status in diabetes, altered platelet function plays a crucial role. Although understanding platelet function abnormalities in diabetes still remains as a challenge, more attention should be focused on platelet function for effective management and the prediction of atherothrombotic events in diabetic patients. This review will provide an overview on the current status of knowledge of platelet function abnormalities and clinical marker of platelet hyperreactivity in patients with diabetes.

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Original Articles

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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Abstract PDF

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

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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

Evaluation of Fasting Plasma Glucose as a Screening for Diabetes Mellitus in Middle-aged Adults of Naju Country.: Jin Hwa Kim, Mi Ah Han, Chol Jin Park, Il Goo Park, Ji Hye Shin, Sang Yong Kim, So Yeon Ryu, Hak Yeon Bae; Korean Diabetes J. 2008;32(4):328-337. Published online August 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.4.328

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Abstract PDF

BACKGROUND
The criteria for the diagnosis of diabetes mellitus have been modified by the American Diabetes Association (ADA) in 1997. The ADA proposed that the diagnosis of diabetes be defined by a fasting plasma glucose (FPG) of 7.0 mmol/L. Disagreement has been reported between criteria based on FPG and postchallenge 2-h plasma glucose (2-h PG). The aim of the present study is to assess the FPG criteria as the diagnostic screening test for diabetes in Korean middle-aged adults in comparison to the 2-h PG criteria. METHODS: Randomly selected 1,731 subjects (679 men and 1,052 women) aged 40~70 years (mean age: 58.4 +/- 7.89 years) without previously diagnosed diabetes completed 75 g oral glucose tolerance test (OGTT). We assessed the prevalence of diabetes mellitus and the level of agreement (kappa statistics) according to the different diagnostic glucose categories. RESULTS: The frequency of newly diagnosed diabetes was 2.7% (n = 51) using the FPG criteria only; 6.4% (n = 120) using the 2-h PG criteria only; and 6.9% (n = 130) using concentrations of > or = 7.0 mmol/L for FPG or > or = 11.1 mmol/L for 2-h PG. Of the 120 subjects with diabetes by the 2-h PG criteria, 65.8% (n = 79) were not diagnosed with diabetes according to FPG concentration. The level of agreement between two diagnostic criteria was low (kappa = 0.268). The receiver operating characterstic (ROC) curve analysis determined FPG of 5.6 mmol/L to yield optimal sensitivity and specificity corresponding to 2-h PG 11.1 mmol/L. CONCLUSION: The findings in this study demonstrate that the discordance between the FPG and 2-h PG criteria in the diagnosis of diabetes in Korean middle-aged adults is large. We suggest that IFG group (FPG 5.6~6.9 mmol/L) were performed 75 g OGTT for diagnosing diabetes mellitus in Korean middle-aged adults.

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The Distribution and Characteristics of Abnormal Findings Regarding Fasting Plasma Glucose and HbA1c - Based on Adults Except for Known Diabetes
Seyoung Kwon, Youngak Na
The Korean Journal of Clinical Laboratory Science.2017; 49(3): 239. CrossRef
Gender differences in metabolic syndrome components among the Korean 66-year-old population with metabolic syndrome
Sangjin Lee, Young Ko, Chanyeong Kwak, Eun-shil Yim
BMC Geriatrics.2016;[Epub] CrossRef
2011 Clinical Practice Guidelines for Type 2 Diabetes in Korea
Seung-Hyun Ko, Sung-Rea Kim, Dong-Joon Kim, Seung-Joon Oh, Hye-Jin Lee, Kang-Hee Shim, Mi-Hye Woo, Jun-Young Kim, Nan-Hee Kim, Jae-Taik Kim, Chong Hwa Kim, Hae Jin Kim, In-Kyung Jeong, Eun-Kyung Hong, Jae-Hyoung Cho, Ji-Oh Mok, Kun-Ho Yoon
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Associated Factors of Impaired Fasting Glucose in Some Korean Rural Adults
Hye Eun Yun, Mi-ah Han, Ki Soon Kim, Jong Park, Myeng Guen Kang, So Yeon Ryu
Journal of Preventive Medicine and Public Health.2010; 43(4): 309. CrossRef
Comparing Survival Functions with Doubly Interval-Censored Data: An Application to Diabetes Surveyed by Korean Cancer Prevention Study
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Effects of Caloric Restriction on the Expression of PGC-1 and PPARs mRNA in Liver of Otsuka Long-Evans Tokushima Fatty Rats.: Sang Yong Kim, Jin Hwa Kim, Hak Yeon Bae, Byoung Rai Lee; Korean Diabetes J. 2006;30(3):161-169. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.161

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Abstract PDF: BACKGROUND
Gluconeogenesis is strongly stimulated during fasting and is aberrantly activated in diabetes mellitus. PPARgamma-coactivator 1 (PGC-1) and Peroxisome proliferator -activated receptors (PPARs) costimulate the expression of key enzymes of gluconeogenetic pathway. This study was performed to evaluate the response to dietary caloric restriction (CR) on the PPARs and PGC-1 expression in liver of diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: Diabetic OLETF rats (male, 24 weeks) and Long-Evans Tokushima Otsuka (LETO) rats (male, 24 weeks) were used in this study. Liver PPARs and PGC-1 mRNA, and blood glucose levels were investigated at 1, 2, and 3 weeks after the beginning of 30% CR. PPARs and PGC-1 mRNA were determined by RT-PCR and blood glucose levels were measured by spectrophotometric assay. RESULTS: The liver PGC-1 mRNA expressions were increased to 19% in non-diabetic LETO rats but significant change was not observed in diabetic OLETF rats by 30% CR. The liver PPARgamma mRNA expressions were not changed in non-diabetic LETO rats but increased to 23% in diabetic OLETF rats by 30% CR. The difference of PPARalpha and PPARbeta mRNA expressions in liver of OLETF and LETO rats were not observed. CONCLUSION: The liver PPARgamma and PGC-1 expression response to CR are altered in OLETF rats compared to in LETO rats. These findings suggested that PPARgamma and PGC-1 expression control system altered in diabetic OLETF rat liver and altered PPARgamma and PCG-1 expression may some roles on the aberrantly activated gluconeogenesis in diabetes mellitus.

Effects of Gutathione on Cyclosporine A-induced Cyotoxicity in Cultured Rat Insulinoma (RIN5mF) Cells.: Dong Hyun Choi, Byoung Rai Lee, Dai Yong Jang, Jong O Kim, Byung Soo Kim, Ki Young Chung, Tae Young Lim, Byung Chul Shin, Hak Yeon Bae; Korean Diabetes J. 2002;26(1):58-64. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Cyclosporin A (CsA) is a immunosuppressive agent that is most widely used in organ transplanted patients to prevent immunorejection, However, it has some side effects, including diabetes mellitus, nephrotoxicity and hypertension. The mechanism of CsA cytotoxicity is unclear but it has been suggested that reactive oxygen species are involved in the cytotoxic reactions. The purpose of this study was to determine the effects of glutathione, as a physiological antioxidant on CsA induced beta-cell toxicity. METHODS: Rat insulinoma (RINm5F) cells were incubated with culture media (RPMI1640) in the presence of CsA and/or buthionine sulfoximine (BSO), which is an inhibitor of r-glutamyl cysteine synthetase, and reduced glutathione. The viable cells were examined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and was determined by a spectrophotometer at a wavelength of 570 nm. RESULTS: Incubating the RINm5F cells with CsA resulted in a decrease in cell viability with increasing dose. This deceased cells viability, induced by CsA was potentiated by BSO treatment. The CsA and BSO induced cells toxicity was reduced significantly by the reduced glutathione. CONCLUSION: The results suggest that pancreatic beta-cell may be injured by CsA and glutathione may have some role in cytotoxicity.

Changes of TBARS and GGTase in Ischemia / Reflowed Kidney of Alloxan-diabetic Rat.: Jong Hoon Chung, Hak Yeon Bae, Jong Hee Cha, Jae Yoon Park, Pyoung Sim Park, Kwang Sam Koh, Byoung Rai Lee; Korean Diabetes J. 1999;23(6):777-784. Published online January 1, 2001

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Abstract PDF: BACKGROUND
To investigate the influence of diabetes mellitus (DM) on ischemia/reflow injury, the contents of thiobarbituric acid reactive substance (TBARS: marker of peroxidative cell injury), and the activity of gamma-glutamyltransferase (GGTase: marker of brush border membrane injury) were measured in ischemia/reflowed kidney of diabetic rats. METHODS: Rats were divided into the 3 groups; control (C), diabetes for 2 weeks (DM2) and diabetes for 4 weeks (DM4), and DM was induced by alloxan (80 mg/kg ip). Left kidney was subjected to 30 min of ischemia and 15 min of blood reflow, and the right kidney was used as a control kidney. The activities of antioxidant enzymes and GGTase, and the contents of TBARS were determined in kidney homogenate. RESULT: Catalase activity in ischemia/reflowed kidney was decreased 20% (p<0.05) in C, 34% (p<0.01) in DM2 and 23% (p<0.01) in DM4, while the change of SOD and GSHPx activities were not observed in kidney of diabetic rats cornpared with group C. TBARS contents, when ischemia/reflow, increased by 23% in C, 19% (p<0.01) in DM2, 16% in DM4, while the activity of GGTase decreased by 40% i#n C, 54% in DM2, and 55% (p<0.01) in kidney of DM4. CONCLUSION: The TBARS contents in ischemia/ reflow kidney of diabetic group showed no change, while GGTase activity was decreased significantly when compared with control group. This study may suggested that in ischemia/reflow kidney, the peroxidative membrane lipid injury was not increased, but the brush border membrane injury was increased by DM.

The Role of Oxidized Low Density Lipoprotein in Atherogenesis.: Hak Yeon Bae; Korean Diabetes J. 1999;23(1):7-11. Published online January 1, 2001

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Abstract PDF: No abstract available.

Plasma Paraoxonase Activities in Type 2 Diabetes Mellitus.: Gyoung Mu Her, Hak Yeon Bae, Byoung Rai Lee; Korean Diabetes J. 1998;22(3):403-409. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Human serum paraoxonase is physically associated with HDL and has been implicated in the detoxification of organophosphate and possibly in the prevention of LDL lipid peroxidation. The activities of paraoxonase and levels of HDL cholesterol were measured in the serum of individuals with type 2 diabetes mellitus in order to evaluate whether a correlation exists between these cnzyme activities and the diabetes mellitus and dliabetic complications. METHODS: Plasma samples were obtain from 60 individuals with type 2 diabetes mellitus(32 women and 28 men; mean age=55.8 yrs) and 30 individuals with healthy control(16 women and 14 men; mean age=-54.1 yrs). Paraoxonase activities were measured spectrophotometrically in 0.1IM Tris-HC1 buffer(pH= 7.4) at 25C with paraoxon as substrate(5.5mM) at 405nm. RESULTS: No significant differences of plasma paraoxonase activity between healthy control and type 2 diabetes mellitus were observed. The significant difference of plasma paraoxonase activity between healthy control and type 2 diabetes mellitus with diabetic complications such as diabetic neuropathy, diabetic retinopathy and diabetic nephropathy were observed. The difference of plasma paraoxonase activity between individuals with type 2 diabetes mellitus without diabetic complication and type 2 diabetes mellitus with diabetic complications was significant. The correlation between paraoxonase activity and HDL-cholesterol, plasma lipoproteins, HbAlc and duration of diabetes were not observed. CONCLUSION: These experimental results suggested that the plasma paraoxonase activity wasnt decreased in individuals with type 2 diabetes mellitus without diabetic complication and the decrement of plasma paraoxonase activity was might be associated with diabetic chronic complications.

The Effect of High Glucose on the Activity of Superoxide Dismutase in NIN6N8a Cells.: Hak Yeon Bae, Byoung Rai Lee, Kwang Sam Kho; Korean Diabetes J. 1998;22(3):271-289. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Reactive oxygen species play a role in the pathogenesis of diabetes mellitus. Hyperglycemia may cause increased production of free radicals, and peroxide formation was increased in high glucose solution. It has been demonstrated that active oxygen species induce antioxidant enzyme expression in some tissues and cells. This study was designed to investigate the effect of high glucose on the activity of superoxide dismutase(SOD) in mouse insulinoma(MIN6N8a) cells. METHODS: MIN6N8a cells were grown in RPMI1640 medium with l0% fetal bovine serum and NIH3T3 cells used as a control cells. The cells were cultured in 5.6 and 22.2 mM glucose cnntained medium. The activities of SOD, catalase and GPX were determined in crude cell extract after 7 days of culture. The levels of CuZn-SOD were also measured with ELISA using anti-CuZn-SOD antibody. RESULTS: In MIN6NSa cells, the catalase activity was very low compared with NIH3T3 cells, but there was no difference in activities of CuZn-SOD and GPX between MIN6N8a cells and NIH3T3 cells. The activity of CuZn-SOD was decreased, while Mn-SOD was increased in MIN6NSa cells cultured with high glucose(22.2 mM) medium compared with those of normoglucose(5.6 mM) medium. However, the level of CuZn-SOD in MIN6NSa cells, when measured with ELISA was high in cells of cultured with high glucose medium. The SOD activity was not effected in MIN6N8a cells cultured with insulin contained medium. CONCLUSION: These experimental result suggest that the CuZn-SOD activity was decreased in MIN6N8a cells cultured with high glucose contained medium and this effect may be resulted from the protein inactivation rather than decrement of protein level.

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