Diabetes & Metabolism Journal

Original Articles

Drug/Regimen
Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial: Jie-Eun Lee, Seung Hee Yu, Sung Rae Kim, Kyu Jeung Ahn, Kee-Ho Song, In-Kyu Lee, Ho-Sang Shon, In Joo Kim, Soo Lim, Doo-Man Kim, Choon Hee Chung, Won-Young Lee, Soon Hee Lee, Dong Joon Kim, Sung-Rae Cho, Chang Hee Jung, Hyun Jeong Jeon, Seung-Hwan Lee, Keun-Young Park, Sang Youl Rhee, Sin Gon Kim, Seok O Park, Dae Jung Kim, Byung Joon Kim, Sang Ah Lee, Yong-Hyun Kim, Kyung-Soo Kim, Ji A Seo, Il Seong Nam-Goong, Chang Won Lee, Duk Kyu Kim, Sang Wook Kim, Chung Gu Cho, Jung Han Kim, Yeo-Joo Kim, Jae-Myung Yoo, Kyung Wan Min, Moon-Kyu Lee; Diabetes Metab J. 2024;48(4):730-739. Published online May 20, 2024; DOI: https://doi.org/10.4093/dmj.2023.0077

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Abstract PDF Supplementary Material PubReader ePub: Background
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Guideline/Fact Sheet
Diabetes Fact Sheets in Korea, 2020: An Appraisal of Current Status: Chan-Hee Jung, Jang Won Son, Shinae Kang, Won Jun Kim, Hun-Sung Kim, Hae Soon Kim, Mihae Seo, Hye-Jung Shin, Seong-Su Lee, Su Jin Jeong, Yongin Cho, Seung Jin Han, Hyang Mi Jang, Mira Rho, Shinbi Lee, Mihyun Koo, Been Yoo, Jung-Wha Moon, Hye Young Lee, Jae-Seung Yun, Sun Young Kim, Sung Rae Kim, In-Kyung Jeong, Ji-Oh Mok, Kun Ho Yoon; Diabetes Metab J. 2021;45(1):1-10. Published online January 13, 2021; DOI: https://doi.org/10.4093/dmj.2020.0254

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175 Crossref

Abstract PDF Supplementary Material PubReader ePub

Background
This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data.
Methods
This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated.
Results
In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes.
Conclusion
The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

Citations

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Drug/Regimen
Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial: Ji Eun Jun, In-Kyung Jeong, Jae Myung Yu, Sung Rae Kim, In Kye Lee, Kyung-Ah Han, Sung Hee Choi, Soo-Kyung Kim, Hyeong Kyu Park, Ji-Oh Mok, Yong-ho Lee, Hyuk-Sang Kwon, So Hun Kim, Ho-Cheol Kang, Sang Ah Lee, Chang Beom Lee, Kyung Mook Choi, Sung-Ho Her, Won Yong Shin, Mi-Seung Shin, Hyo-Suk Ahn, Seung Ho Kang, Jin-Man Cho, Sang-Ho Jo, Tae-Joon Cha, Seok Yeon Kim, Kyung Heon Won, Dong-Bin Kim, Jae Hyuk Lee, Moon-Kyu Lee; Diabetes Metab J. 2020;44(1):78-90. Published online June 20, 2019; DOI: https://doi.org/10.4093/dmj.2018.0265

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Abstract PDF Supplementary Material PubReader

Background

Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia.

Methods

This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment.

Results

After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups.

Conclusion

The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

Citations

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Current trends in solving the problem of residual cardiovascular risk
N. Yu. Obedkova, A. A. Guslyakova, G. S. Mal, E. G. Obedkov
Meditsinskiy sovet = Medical Council.2024; (6): 155. CrossRef
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Tianjiao Wang, Xin Zhang, Na Zhou, Yuxuan Shen, Biao Li, Bingshu E. Chen, Xinzhi Li
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Nutraceutical support in the prevention and treatment of cardiovascular diseases
E. V. Gracheva, E. A. Starovoytova, E. S. Kulikov, N. A. Kirillova, S. V. Fedosenko, M. A. Balaganskaya, D. V. Kromka
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Effect of coadministration of omega-3 fatty acids with glimepiride on glycemic control, lipid profile, irisin, and sirtuin-1 in type 2 diabetes mellitus patients: a randomized controlled trial
Rehab H. Werida, Aalaa Ramzy, Youssri Nassief Ebrahim, Maged Wasfy Helmy
BMC Endocrine Disorders.2023;[Epub] CrossRef
The Effect of Dietary Interventions on Hypertriglyceridemia: From Public Health to Molecular Nutrition Evidence
Karla Paulina Luna-Castillo, Xochitl Citlalli Olivares-Ochoa, Rocío Guadalupe Hernández-Ruiz, Iris Monserrat Llamas-Covarrubias, Saraí Citlalic Rodríguez-Reyes, Alejandra Betancourt-Núñez, Barbara Vizmanos, Erika Martínez-López, José Francisco Muñoz-Valle
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The effect of omega-3 fatty acids and its combination with statins on lipid profile in patients with hypertriglyceridemia: A systematic review and meta-analysis of randomized controlled trials
Yunjiao Yang, Wen Deng, Yanmei Wang, Tongyi Li, Yiding Chen, Cong Long, Qing Wen, Yue Wu, Qiu Chen
Frontiers in Nutrition.2022;[Epub] CrossRef
Comparison of the Efficacy and Safety of Atorvastatin 40 mg/ω-3 Fatty Acids 4 g Fixed-dose Combination and Atorvastatin 40 mg Monotherapy in Hypertriglyceridemic Patients who Poorly Respond to Atorvastatin 40 mg Monotherapy: An 8-week, Multicenter, Random
Jong Shin Woo, Soon Jun Hong, Dong Hoon Cha, Kee Sik Kim, Moo Hyun Kim, Jun-Won Lee, Myung Ho Jeong, Jin-Ok Jeong, Jun-Hee Lee, Doo Soo Jeon, Eun Joo Cho, Soon Kil Kim, Jun Kwan, Chang Gyu Park, Hae Young Lee, Taek Jong Hong, Jinho Shin, Ho Joong Youn, Do
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All-Cause Mortality and Cardiovascular Death between Statins and Omega-3 Supplementation: A Meta-Analysis and Network Meta-Analysis from 55 Randomized Controlled Trials
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Clinical Diabetes & Therapeutics
Efficacy and Safety of Voglibose Plus Metformin in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial: Tae Jung Oh, Jae Myung Yu, Kyung Wan Min, Hyun Shik Son, Moon Kyu Lee, Kun Ho Yoon, Young Duk Song, Joong Yeol Park, In Kyung Jeong, Bong Soo Cha, Yong Seong Kim, Sei Hyun Baik, In Joo Kim, Doo Man Kim, Sung Rae Kim, Kwan Woo Lee, Jeong Hyung Park, In Kyu Lee, Tae Sun Park, Sung Hee Choi, Sung Woo Park; Diabetes Metab J. 2019;43(3):276-286. Published online December 7, 2018; DOI: https://doi.org/10.4093/dmj.2018.0051

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Background

Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus.

Methods

A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24.

Results

The reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of <6.5% (P=0.002) or <7% (P=0.039). Glycemic variability was also significantly improved with vogmet treatment, estimated by M-values (P=0.004). Gastrointestinal adverse events and hypoglycemia (%) were numerically lower in the vogmet-treated group. Moreover, a significant weight loss was observed with vogmet treatment compared with metformin (−1.63 kg vs. −0.86 kg, P=0.039).

Conclusion

Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.

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Mónica Aideé Díaz-Román, Juan José Acevedo-Fernández, Gabriela Ávila-Villarreal, Elizabeth Negrete-León, A. Berenice Aguilar-Guadarrama
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Efficacy and Safety of DPP-4 Inhibitors and Metformin Combinations in Type 2 Diabetes: A Systematic Literature Review and Network Meta-Analysis
Rongping Chen, Jing Li, Danqi Chen, Weiheng Wen, Susu Zhang, Jitong Li, Yuting Ruan, Zhen Zhang, Jia Sun, Hong Chen
Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 2471. CrossRef
Metformin-Associated Gastrointestinal Adverse Events Are Reduced by Probiotics: A Meta-Analysis
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YAP/TAZ axis was involved in the effects of metformin on breast cancer
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Diabetes Remission
Ashok Kumar, Shubha Laxmi Margekar, Ravi Kumar
Indian Journal of Medical Specialities.2023; 14(1): 3. CrossRef
Analysis of Reports Sent to the Portuguese Pharmacovigilance System and Published Literature Regarding the Safety of Metformin in the Elderly
Beatriz Esteves, Cristina Monteiro, Ana Paula Coelho Duarte
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Xiaogang He, Xiang Han, Jiaping Yu, Yulong Feng, Ganghui Chu
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy.2022; 268: 120601. CrossRef
Insulin autoimmune syndrome in patients with type 2 diabetes: A report of two cases
Y. Shin, T.J. Oh, S.H. Choi, H.C. Jang
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Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study
Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin, Jeong Mi Kim, Min Hee Jang, Kyung Ae Lee, Ju Hyung Lee, Seung Min Chung, Young Sang Lyu, Jin Hwa Kim, Sang Yong Kim, Jung Eun Jang, Tae Nyun Kim, Sung Woo Kim, Eonju Jeon, Nan Hee Cho, Mi-Kyung Ki
Diabetes & Metabolism Journal.2021; 45(5): 675. CrossRef
Quantifying Remission Probability in Type 2 Diabetes Mellitus
Sanjay Kalra, Ganapathi Bantwal, Nitin Kapoor, Rakesh Sahay, Saptarshi Bhattacharya, Beatrice Anne, Raju A Gopal, Sunil Kota, Ashok Kumar, Ameya Joshi, Debmalya Sanyal, Mangesh Tiwaskar, Ashok Kumar Das
Clinics and Practice.2021; 11(4): 850. CrossRef
The effect of voglibose on metabolic profiles in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials
Peyman Nowrouzi-Sohrabi, Reza Tabrizi, Shahla Rezaei, Fatemeh Jafari, Kamran Hessami, Mehdi Abedi, Mohammad Jalali, Pedram Keshavarzi, Saeed Shahabi, Ali Asghar Kolahi, Kristin Carson-Chahhoud, Amirhossein Sahebkar, Saeid Safiri
Pharmacological Research.2020; 159: 104988. CrossRef
Role of Intestinal Microbiota in Metabolism of Voglibose In Vitro and In Vivo
Mahesh Raj Nepal, Mi Jeong Kang, Geon Ho Kim, Dong Ho Cha, Ju-Hyun Kim, Tae Cheon Jeong
Diabetes & Metabolism Journal.2020; 44(6): 908. CrossRef
Response: Efficacy and Safety of Voglibose Plus Metformin in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial (Diabetes metab J 2019;43;276-86)
Tae Jung Oh, Sung Hee Choi
Diabetes & Metabolism Journal.2019; 43(4): 547. CrossRef
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Hannah Seok, Tae Seo Sohn
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Serum Adiponectin and Type 2 Diabetes: A 6-Year Follow-Up Cohort Study: Sun Ha Jee, Chul Woo Ahn, Jong Suk Park, Chang Gyu Park, Hyon-Suk Kim, Sang-Hak Lee, Sungha Park, Myoungsook Lee, Chang Beom Lee, Hye Soon Park, Heejin Kimm, Sung Hee Choi, Jidong Sung, Seungjoon Oh, Hyojee Joung, Sung Rae Kim, Ho-Joong Youn, Sun Mi Kim, Hong Soo Lee, Yejin Mok, Eunmi Choi, Young Duk Yun, Soo-Jin Baek, Jaeseong Jo, Kap Bum Huh; Diabetes Metab J. 2013;37(4):252-261. Published online August 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.4.252

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Background

Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women.

Methods

A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used.

Results

Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in men or women with IFG after adjustment for fasting glucose and other confounders.

Conclusion

A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful.

Citations

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Adiponectin and metabolic cardiovascular diseases: Therapeutic opportunities and challenges
Xiaotian Lei, Sheng Qiu, Gangyi Yang, Qinan Wu
Genes & Diseases.2023; 10(4): 1525. CrossRef
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Young-Sang Kim, Soo-Hyun Lee, Seung Geon Park, Bo Youn Won, Hyejin Chun, Doo-Yeoun Cho, Moon-Jong Kim, Ji Eun Lee, Ji-Hee Haam, Kunhee Han
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Sahar M. El-Haggar, Wael F. Farrag, Fedaa A. Kotkata
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Low Density Lipoprotein Cholesterol Target Goal Attainment Rate and Physician Perceptions about Target Goal Achievement in Korean Patients with Diabetes: Jenie Yoonoo Hwang, Chang Hee Jung, Woo Je Lee, Cheol Young Park, Sung Rae Kim, Kun-Ho Yoon, Moon Kyu Lee, Sung Woo Park, Joong-Yeol Park; Diabetes Metab J. 2011;35(6):628-636. Published online December 26, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.6.628

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Background

This study aims to investigate the discrepancy between clinicians' perceptions and actual achievement rates of low density lipoprotein cholesterol (LDL-C) in Korean patients with diabetes according to updated American Diabetes Association (ADA)/American College of Cardiology Foundation (ACC) recommendations.

Methods

This is a multi-center, retrospective, non-interventional, observational study. Diabetic patients aged 18 years or older were eligible if they had been diagnosed with hypercholesterolemia or were receiving a lipid-lowering therapy between May 2010 and August 2010. The information was obtained by reviewing medical records and using a self-completed questionnaire to examine physician perceptions.

Results

A total of 2,591 subjects who satisfied the inclusion criteria were enrolled. Highest-risk and high-risk patients accounted for 61.9% and 38.1% of the patients, respectively. Although most (96.3%) underwent a statin monotherapy or a statin-based combination therapy, just 47.4% of patients attained the LDL-C target. However, the physicians' perceptions on target achievement rate (70.6%) were different from the actual results (47.4%). Many patients (65.3%) remained on the starting doses of statins, despite evidence of poor achievement of lipid goals.

Conclusion

Only less than half of patients with diabetes attained the LDL-C goal. The surveys showed that poor physician performance might be due to the lack of recognition on ADA/ACC consensus causing a low LDL-C target attainment rate. Therefore, changes in doctor perception are needed to attain target LDL-C level and reduce cardiovascular risk in Korean patients with diabetes.

Citations

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Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
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Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
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Current Status of Low-Density Lipoprotein Cholesterol Target Achievement in Patients with Type 2 Diabetes Mellitus in Korea Compared with Recent Guidelines
Soo Jin Yun, In-Kyung Jeong, Jin-Hye Cha, Juneyoung Lee, Ho Chan Cho, Sung Hee Choi, SungWan Chun, Hyun Jeong Jeon, Ho-Cheol Kang, Sang Soo Kim, Seung-Hyun Ko, Gwanpyo Koh, Su Kyoung Kwon, Jae Hyuk Lee, Min Kyong Moon, Junghyun Noh, Cheol-Young Park, Sung
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Ke Li, Meng-Meng Liu, Xin Yang, Li Chen, Hui Geng, Wei Luo, Jie Ma
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Low-density lipoprotein cholesterol goal attainment rates in high-risk patients with cardiovascular diseases and diabetes mellitus in Korea: a retrospective cohort study
Ye Seul Yang, Bo Ram Yang, Mi-Sook Kim, Yunji Hwang, Sung Hee Choi
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Sang-Hak Lee, Woo-Hyuk Song, Myung Ho Jeong, Seung-Ho Hur, Dong Woon Jeon, Wonju Jeung, Anselm K Gitt, Martin Horack, Ami Vyas, Dominik Lautsch, Baishali Ambegaonkar, Philippe Brudi, Yangsoo Jang
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Jae-Woo Lee, Na-Young You, Yeseul Kim, Yonghwan Kim, Joungyoun Kim, Hee-Taik Kang
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Shuiping Zhao, Daoquan Peng
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Management of Blood Pressure in Patients with Type 2 Diabetes Mellitus: A Nationwide Survey in Korean: Mi Hae Seo, Woo Je Lee, Cheol Young Park, Sung Rae Kim, Joong Yeol Park, Kun-Ho Yoon, Moon Kyu Lee, Sung Woo Park; Diabetes Metab J. 2011;35(4):348-353. Published online August 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.4.348

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Background

Hypertension is common in patients with type 2 diabetes, affecting up to 60% of patients. The Korean Diabetes Association performed a nationwide survey about prevalence, awareness and control of hypertension among diabetic Koreans.

Methods

The current survey included 3,859 diabetic patients recruited from 43 hospitals in Korea. Age, gender, height, weight and blood pressure (BP) were measured by standard methods. Data on fasting plasma glucose, glycosylated hemoglobin (HbA1c), awareness of hypertension, and compliance of antihypertensive medication were collected via interview and reviewed using patient medical records.

Results

A total of 57.5% of all patients were >60 years old. Their mean HbA1c was 7.6±1.5%. Among antihypertensive medication users, 39.9% had <130 mm Hg and <80 mm Hg, whereas 60.1% had ≥130 mm Hg or ≥80 mm Hg. The answer "BP is under good control" was given by 75.1% of the antihypertensive medication users. Out of these patients, 26.4% had <130 mm Hg and <80 mm Hg, whereas 73.6% had ≥130 mm Hg or ≥80 mm Hg. A total of 75.5% of antihypertensive medication users answered that they had taken their antihypertensive medication every day for the past 2 weeks. "Forgetfulness" was most frequently the reason of non-compliance for patients that did not take their antihypertensive medication regularly.

Conclusion

Approximately one third of the patients with diabetes were found to reach target blood pressure control in the 43 hospitals across Korea. Stricter control is needed to reduce severe complications of diabetes in Korea.

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Islet transplantation is an alternative potential strategy to cure type 1 diabetes mellitus. However, two or more donors are usually needed for one recipient because a substantial part of the graft becomes nonfunctional due to several factors including hypoxia. Though hypoxic exposure of pancreatic beta cells has been reported to induce apoptotic cell death, the molecular processes involved in hypoxia-induced cell death are poorly understood. In type I diabetes, Nitric Oxide (NO) is known as an important cytokine, involved in the pathogenesis of beta cell dysfunction. Pancreatic beta cells are sensitive to the induction of inducible nitric oxide synthase (iNOS) when stimulated by TNF-a or IL-1beta. But contribution of iNOS in response to hypoxia is not yet fully understood. METHODS: Mouse insulinoma cells (MIN6) were incubated in an anaerobic chamber (75% N2/15% CO2/5% H2) for up to 12 hours. Cell viability was measured after AO/PI staining. Caspase-3 activation was also determined using Western blot analysis. Nitric Oxide (NO) release into culture medium was measured using a Griess reagent. The expression of iNOS and PDX-1 mRNA and iNOS protein was examined using real time PCR and Western blot analysis. RESULTS: Marked cell death was observed within 6 hours after hypoxic exposure of MIN6 cells (control, < 5%; 2 hr, 11.0+/-7.6%; 6 hr, 46.2+/-12.8%, P < 0.05). Immunoreactivity to activated caspase-3 was observed at 2, 4 and 6 hrs. NO production was increased in a time dependent manner. Expression of iNOS mRNA and protein was significantly increased at 4 and 6 hour after hypoxia. iNOS expression was confirmed by immunostaining. Of note, Pdx-1 mRNA expression was markedly attenuated by hypoxic treatment. Pretreatment with a selective iNOS inhibitor, 1400 W, significantly prevented beta cell death induced by hypoxic injury. CONCLUSION: Our data suggest that iNOS-NO play an important role in hypoxic injury to MIN6 cells. Therefore, iNOS-NO might be a potential therapeutic target for improving engraftment of the transplanted islets and suppression of iNOS would be helpful for prevention of beta cells damage to hypoxic injury.

Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus.: Seung Hyun Ko, Hyuk Sang Kwon, Jung Min Lee, Sung Rae Kim, Jae Hyung Cho, Ki Dong Yoo, Yong Moon Park, Won Chul Lee, Ki Ho Song, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yu Bai Ahn; Korean Diabetes J. 2006;30(3):226-235. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.226

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BACKGROUND
Diabetic autonomic neuropathy has a significant negative impact on survival and quality of life in type 2 diabetic patients. Especially cardiovascular autonomic neuropathy (CAN) is clinically important, because of its correlation to cardiovascular death. Therefore, we investigated the prevalence of CAN in Korean type 2 diabetic patients. METHODS: 1798 type 2 diabetic patients, 727 males and 1071 females, visited Diabetes Clinic at St. Vincent Hospital, Korea, were included from January 2001 to December 2005. Clinical evaluation, laboratory test and assessment of diabetic complication were completed. Standard test for CAN were performed: 1) heart rate variability (HRV) during deep breathing (E/I ratio) 2) Valsalva maneuver 3) 30:15 ratio 4) blood pressure response to standing. CAN score was determined according to the results of the test as following: 0 = normal, 1 = abnormal. RESULTS: Mean age and diabetic duration of patients were 56.7 +/- 10.9, and 9.4 +/- 7.5 years. Normal and abnormal CAN were detected in 815 (45.3%) and 983 (54.7%) of the patients, respectively. Abnormal E/I, valsalva, and 30:15 ratio were found in 333 (18.5%), 717 (39.9%), and 546 (30.4%) patients, respectively. Age, diabetic duration, postprandial hyperglycemia, HbA1c, C-reactive protein, and microalbumuria levels were significantly different between normal and abnormal CAN groups. 49 (6.0%) patients of normal and 100 (10.2%) patients of abnormal CAN group showed previous attack of stroke (P = 0.004). In addition, diabetic foot was more frequent in patients with CAN (normal vs. abnormal, 14 (1.7%) vs. 73 (7.4%), P < 0.05). CONCLUSION: CAN is frequently found in Korean type 2 diabetic patients. It was associated with diabetic duration, uncontrolled diabetes, increased albumin excretion rate, presence of retinopathy, postprandial hyperglycemia.

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Clustering Characteristics of Risk Variables of Metabolic Syndrome in Korean Rural Populations.: Yong Moon Park, Hyuk Sang Kwon, Sun Young Lim, Jin Hee Lee, Sung Rae Kim, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yong Gyu Park, Dong Suk Kim, Kwang ho Meng, Won Chul Lee; Korean Diabetes J. 2006;30(3):177-189. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.177

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BACKGROUND
The risks of both type 2 diabetes mellitus and cardiovascular disease are mainly associated with the metabolic syndrome which is characterized by clustering of metabolic risk factors, including abdominal obesity, glucose intolerance, hypertension, and dyslipidemia. This study aimed to examine the relations among metabolic risk variables and the underlying structure of the metabolic syndrome that unites related components. METHODS: Subjects were selected by stratified random cluster sampling among persons aged over 40 years from a rural area. Waist circumference, BMI, fasting glucose, fasting insulin, triglycerides, HDL cholesterol, systolic blood pressure, and diastolic blood pressure were used as risk variables of metabolic syndrome. Factor analysis, a multivariate correlation statistical technique, was performed on a dataset from nondiabetic 3,443 men and women without history of coronary heart disease. RESULTS: Exploratory factor analysis identified three factors in both gender (obesity, hypertension, and dyslipidemia-insulin resistance in men; obesity-insulin resistance, hypertension, and dyslipidemia in women). Fasting insulin was a common contributor to the structure of metabolic syndrome in male subjects, smokers and alcohol drinking group. Confirmatory factor analysis based on the results of exploratory factor analysis revealed that metabolic syndrome was represented primarily by obesity factor in men, obesity-insulin resistance factor in women, and that dyslipidemia factor was highly correlated with obesity factor in men, with insulin resistance factor in women. CONCLUSION: Underlying structure of metabolic syndrome was different between men and women, and obesity might be a primary target for prevention of both type 2 diabetes mellitus and cardiovascular disease in Korea.

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Development of Adult Porcine Islet Isolation Method for Xenotransplantation.: Sung Rae Kim, Kun Ho Yoon, Hyuk Sang Kwon, Sun Hee Suh, Seung Hyun Ko, Jung Min Lee, Soon Jib Yoo, Yoo Bae Ahn, Ki Ho Song, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2004;28(2):75-87. Published online April 1, 2004

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Abstract PDF: BACKGROUND
AND PURPOSE: Xenotransplantation using porcine islet cells might be an alternative to allotransplantation, which has been limited due to the lack of donors. Various researches using porcine islet cells have been performed in foreign countries; however, they have never been studies in Korea. Therefore, the purpose of this study was to explore the possibility of thise new treatment for cases of diabetes by establishing of improved islet isolation skill. METHODS: The pancreas and islets were extracted from pigs weighing around 100kg. To establish an islet isolation method, the islet yield, purity and the distribution size of the isolated islets were step wise compared in various ways, and then the superior method adopted. To determine the conveyance method after organ extraction, the conveyance method of pouring collagenase P was compared with the conveyance method of injecting Custidol. For digestion, the mechanical shaking and static incubation methods were also compared. To isolate islets from the digested pancreata, isolation methods were analyzed using 3 and 4 layers' Ficoll. The islet yield was appraised after their isolation using the optimized islet isolation method. To assess the results of the islet isolation, appraised the purity and the survival rates of cells, the insulin secretion resulting from the glucose stimulation test was examined. RESULTS: The method of injecting 4degrees C Custidol was effective for the conveyance and storage of the isolated pancreas in comparison with an injection of collagenase P(3465+/-1488 IEQ/g pancreas vs. 48+/-1.7 IEQ/g pancreas, p<0.01). The digestion method was superior to the mechanical shaking method at keeping a stable condition(3465+/-1488 IEQ/g pancreas vs. 1265+/-141.4 IEQ/g pancreas, p<0.01). Ficoll isolation using 3 layers gave the same results as using 4 layers. The average weights of the isolate Pancreatic islets was 23.8+/-3.3g. The numbers of islets per gram was 3465+/-1488.2(IEQ), with a the purity of 86.3+/-2.0%, and a survival rate of over 95%. The insulin secretion caused by glucose stimulation substantially increased in concentration from 24 to 72 hours(24hr: 5mM 3.12mU/mL --< 20mM 6.79mU/mL(2.17 fold), 72hr: 5mM 2.38mU/mL --< 9.93mU/mL(4.17fold))

The Effect of Nitric Oxide on Insulin Binding and Insulin Receptor Recycling in Bovine Aortic Endothelial Cells.: Hyuk Sang Kwon, Oak Kee Hong, Hee Soo Kim, Jung Min Lee, Sung Rae Kim, Sung Dae Moon, Sang Ah Jang, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2003;27(3):213-227. Published online June 1, 2003

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Abstract PDF: BACKGROUND
The coexistence of insulin resistance and endothelial dysfunction is commonly observed in a variety of metabolic and cardiovascular disorders, including athero-sclerosis and type 2 diabetes mellitus. Because nitric oxide (NO), or nitric oxide synthase (NOS), has been suggested as a significant contributing factor in the development of endothelial dysfunction and insulin resistance, reactive NO or NOS were investigated to see if they contribute to the insulin internalization pathway. METHODS: The production of NO (Nitrite), the expression of eNOS (endothelial NOS), insulin binding and the insulin receptor internalization and recycling, following 48 hours of incubation with bradykinin (BK), acetylcholine (Ach), NG-monomethyl- L-arginine (L-NMMA) and N-nitro-L-arginine methylester (L-NAME) in Bovine aortic endothelial cells (BAECs), were examined. RESULTS: The results were as follows: 1. In relation to the time course, the production of eNOS was increased, but was decreased after 8 hours of incubation. The production of eNOS in the L-NMMA and L-NAME treated groups was significantly decreased compared with that of the controls (p<0.05). 2. The specific insulin bindings to the receptors of the endothelial cells were maximized within 20 mins, and then decreased. At 20 mins, the binding rate of the L-NMMA treated group was significantly decreased compared to that of the controls. At a concentration of 0.4ng/ml of unlabelled insulin, the specific insulin binding of the L-NMMA treated group was significantly decreased compared to that of the controls (p<0.05). 3. The internalization of 125I-insulin into the endothelial cells, as assessed by the acid washing dissociation method, occurred rapidly. The internalized radioactivity of 125I-insulin, at 20 mins, was significantly increased in the BK and Ach groups compared with the controls (p<0.05). 4. The recycling of the internalized insulin receptors showed no significant differences between the study groups, but the recycling was slightly delayed compared with controls in the Ach group. CONCLUSION: In conclusion, the NO generating substances, BK and Ach, and the inhibitory substance, L-NMMA, may influence the binding and internalization of insulin-insulin receptors. Our results suggest that NO might contribute to the transcytosis of insulin in BAECs

Selective beta-Cell Loss and alpha-Cell Expansion in Islets of Type 2 Diabetic Patients.: Jae Hyoung Cho, In Kyu Lee, Kun Ho Yoon, Seung Hyun Ko, Sun Hee Suh, Jung Min Lee, Sung Rae Kim, Yoo Bae Ahn, Jong Min Lee, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2001;25(2):164-177. Published online April 1, 2001

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Abstract PDF: BACKGROUND
It has been reported that a decrease in the beta-cell mass, may play a major role in the development of type 2 diabetes. Some stimuli that cause beta-cell loss can stimulate neogenesis from precursors as well as replication of matured beta-cells. In an animal-based studies reported that alpha-cells can also be produced in the course of alpha-cell neogenesis, after being treated with streptozotocin. Through this research, we attempted to determine the change of beta-cell mass according to the changes in alpha-cell mass and to characterize the size of the beta-cell nucleus observed in type 2 diabetes. METHOD: To estimate the relative fraction of alpha- and beta-cell mass in the pancreas, we counted beta-cells and alpha-cells by point count method. We also performed a double immunohistochemical staining with glucagon and insulin antibodies to calculate the ratio between these two cells area in the pancreas (A/B ratio). In order to measure the size of the beta-cell nucleus, an immunofluorescence staining of the nucleus and insulin was carried out. Data were gathered from type 2 diabetic subjects (n=19) and normal controls (n=8). RESULTS: Although there was no statistical difference, we observed the tendency of decrease of beta-cell mass and increase of alpha-cell mass in the pancreas of type 2 diabetic patients. The ratio of alpha-to beta-cell area in islet (A/B ratio) increased to 0.81+/-0.76 in diabetic patients compared to control with 0.26+/-0.25 (p<0.01). The mean of the A/B ratios of the islets more than 22,000 micro m2 was 1.64+/-1.10, whereas that of the islets less than 22,000 micro m2 was 0.73+/-0.67 in type 2 diabetic patients (p<0.01). The size of the beta-cell nucleus in both diabetic subjects and normal controls was bigger than that of exocrine cells (p<0.05) and 2.9% of beta-cells in type 2 diabetic subjects showed substantially enlarged nuclei more than M+5SD (M and SD means the average and standard deviation of nucleus size of exocrine cells, respectively) whereas this type of nucleus was found in only 0.5% of beta-cells in normal controls (p<0.05). CONCLUSION: The islet pathology in type 2 diabetes could be characterized by an expansion of alpha-cells associated with the selective loss of beta-cells. Some beta-cells found in diabetes showed a significant increase in size of the nucleus. Through the results from this study, we postulate that enlarged beta-cell nucleus and reverse of A/B ratio in the islets could be a marker of early senescence of beta-cells in patients with type 2 diabetes mellitus.

Effects of Cilostazol on Insulin Resistance in OLETF Rats.: Sung Rae Kim, Ki Hyun Baek, Seung Hyun Ko, Jung Min Lee, Sang Ah Chang, Yoo Bae Ahn, Soon Jib Yoo, Jong Min Lee, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2001;25(1):63-70. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Insulin resistance is one of the major pathophysiology of type 2 diabetes mellitus. It is reported that cilostazol and cyclic AMP phosphodiesterase inhibitor has the anti-platelet effect as well as an improvement of hypertriglyceridemia in addition to vasodilatation. Furthermore, the previous reports indicated that there is a positive relationship between insulin resistance and dyslipidemia. Thus, we investigated the effects of cilostazol on insulin resistance in OLETF rats using the euglycemic hyperinsulinemic glucose clamp technique, and lipid levels. METHODS: Fifteen five months old OLETF rats were fed for 4 weeks(8 treated with cilostazol and 7 were control), and compare to 20 same aged LETO rats (8 treated with cilostazol and 12 were control) through the glucose infusion rate on euglycemic hyperinsulinemic glucose clamp and lipid profiles. RESULTS: The glucose infusion rate was higher in the cilostazol treated OLETF rats than in the non-cilostazol treated OLETF rats (0.021+/-0.0031 vs 0.027+/-0.0036 mL/min). The levels of free fatty acids (2424.8+/-652.7 vs 1061.8+/-223.2 Eq/L), total cholesterol (145.7+/-17.9 vs 115.4+/-7.6 mg/dL) and triglyceride (146.5+/-46.6 vs 76.1+/-12.5 mg/dL) of cilostazol treated OLETF rats were significantly lower than those of non-cilostazol treated OLETF rats. CONCLUSION: This study result suggest that cilostazol may improve the insulin resistance through the improvement of dyslipidemia in OLETF rats.

Changes in the Amount and Function of Gi Protein in the Liver Cells of Streptozotocin-Induced Diabetic Rats.: Sun Myeong Ock, Hyun Shik Son, Oak Kee Hong, Jung Min Lee, Sung Rae Kim, Sang Ah Chang, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2000;24(6):666-677. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The functional and expressional changes of Gi proteins in diabetes have been investigated extensively, no agreement has been reached in the results. Moreover, studies using rats with different diabetic duration, and using subunits (Gialpha) of Gi proteins are lacking in literatures. Thus, we assessed the changes according to the duration of diabetes and examined the expressional changes of Gialphaand functional changes of Gi proteins in hepatocytes from streptozotocin-induced diabetic rats. METHODS: Male Sprague-Dawley rats were injected with streptozotocin to induce diabetes ; 1, 2, 3 and 5 weeks after the onset of diabetes, livers from the control and diabetic rats were fractionated into homogenate, interface, and plasma membrane. The levels of Gialpha1&2, Gialpha3 were quantified with western blots in each fraction. The functional changes of Gi proteins were evaluated by performing pertussis toxin-catalyzed ADP-ribosylation and measuring GTP S binding activity. RESULTS: 1) Gialpha2 and Gialpha3 were present mainly in the plasma membrane of hepatocytes in the diabetic and control rats, but the levels of these subunits were significantly higher in the diabetic rates than in the control rats (p<0.01). The levels of these subunits were not affected by the duration of diabetes. 2) In streptozotocin-induced diabetic rats, the levels of ADP-ribosylation of Gi proteins in liver plasma membranes decreased when pertussis toxin-catalyzed ADP-ribosylation was performed with liver tissues. However, the levels of these proteins were not affected by the duration of diabetes. 3) For the GTP S binding activity of Gi proteins in liver plasma membranes, the diabetic rats showed significantly less activity than the control rats (p<0.01). However, the activity was not affected by the duration of diabetes. The activity was somewhat restored by the insulin treatment of liver plasma membranes in diabetic rats. CONCLUSION: These results suggest that the insulin-deficient diabetic state induces the quantitative and functional changes in Gi proteins of hepatocytes regardless of the duration of diabetes. Therefore, these changes in Gi proteins may be the important compensatory reactions for the insulin resistance occurring in the insulin deficient state.

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