Diabetes & Metabolism Journal

Original Articles

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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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

Citations to this article as recorded by

Association Between Omega‐3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose–Response Meta‐Analysis of Randomized Controlled Trials
Tianjiao Wang, Xin Zhang, Na Zhou, Yuxuan Shen, Biao Li, Bingshu E. Chen, Xinzhi Li
Journal of the American Heart Association.2023;[Epub] CrossRef
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
Rational Pharmacotherapy in Cardiology.2023; 19(3): 298. CrossRef
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
Nutrients.2022; 14(5): 1104. CrossRef
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
Clinical Therapeutics.2021; 43(8): 1419. CrossRef
All-Cause Mortality and Cardiovascular Death between Statins and Omega-3 Supplementation: A Meta-Analysis and Network Meta-Analysis from 55 Randomized Controlled Trials
Jeongseon Kim, Tung Hoang, Ji-Myung Kim, So Young Bu, Jeong-Hwa Choi, Eunju Park, Seung-Min Lee, Eunmi Park, Ji Yeon Min, In Seok Lee, So Young Youn, Jee-Young Yeon
Nutrients.2020; 12(10): 3203. CrossRef

Complications
Association between Serum Cystatin C and Vascular Complications in Type 2 Diabetes Mellitus without Nephropathy: Hye Jeong Kim, Dong Won Byun, Kyoil Suh, Myung Hi Yoo, Hyeong Kyu Park; Diabetes Metab J. 2018;42(6):513-518. Published online October 15, 2018; DOI: https://doi.org/10.4093/dmj.2018.0006

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Background

Recent studies have correlated serum cystatin C (CysC) with vascular complications, but few studies have investigated this correlation in diabetes patients without nephropathy. This study aimed to evaluate if higher serum CysC levels increase the risk for vascular complications in type 2 diabetes mellitus patients with normal renal function or mild renal impairment.

Methods

A total of 806 consecutive patients with type 2 diabetes mellitus who were admitted to the diabetes center of Soonchunhyang University Hospital for blood glucose control were retrospectively reviewed. Patients with nephropathy were excluded. Subjects were categorized into quartiles of serum CysC levels (Q1, ≤0.65 mg/L; Q2, 0.66 to 0.79 mg/L; Q3, 0.80 to 0.94 mg/L; and Q4, ≥0.95 mg/L).

Results

The proportion of patients with diabetic retinopathy (DR) (P for trend <0.001), coronary heart disease (CHD) (P for trend <0.001), and stroke (P for trend <0.001) increased across the serum CysC quartiles. After adjustment for confounding factors, the highest serum CysC level remained a significant risk factor for DR (odds ratio [OR], 1.929; 95% confidence interval [CI], 1.007 to 4.144; P=0.040). Compared with Q1, a significant positive association was observed between serum CysC and CHD in Q2 (OR, 7.321; 95% CI, 1.114 to 48.114; P=0.012), Q3 (OR, 6.027; 95% CI, 0.952 to 38.161; P=0.020), and Q4 (OR, 8.122; 95% CI, 1.258 to 52.453; P=0.007). No associations were observed between CysC and stroke after additional adjustment for confounding variables.

Conclusion

Serum CysC levels are independently associated with DR and CHD, suggesting that CysC may be useful for identifying type 2 diabetes mellitus patients without nephropathy who are at high risk for vascular complications.

Citations

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A systematic literature review of machine learning based risk prediction models for diabetic retinopathy progression
Tiwalade Modupe Usman, Yakub Kayode Saheed, Augustine Nsang, Abel Ajibesin, Sandip Rakshit
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Serum cystatin C for risk stratification of prediabetes and diabetes populations
Kun Xiong, Shiran Zhang, Pingting Zhong, Zhuoting Zhu, Yanping Chen, Wenyong Huang, Wei Wang
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(11): 102882. CrossRef
Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
Jing Wei, Jincheng Zhang, Yanan Shi, Huiqin Zhang, Yan Wu
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Diagnostic circulating biomarkers to detect vision‐threatening diabetic retinopathy: Potential screening tool of the future?
Karen Frudd, Sobha Sivaprasad, Rajiv Raman, Subramanian Krishnakumar, Yeddula Rebecca Revathy, Patric Turowski
Acta Ophthalmologica.2022;[Epub] CrossRef
Association between circulating cystatin C and hyperuricemia: a cross-sectional study
Yanjun Guo, Hangkai Huang, Yishu Chen, Chao Shen, Chengfu Xu
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Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy
Sarega Gurudas, Karen Frudd, Jayapal Jeya Maheshwari, Yeddula Rebecca Revathy, Sobha Sivaprasad, Shruthi Mahalakshmi Ramanathan, Vignesh Pooleeswaran, A. Toby Prevost, Eleni Karatsai, Sandra Halim, Shruti Chandra, Paul Nderitu, Dolores Conroy, Subramanian
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A Cross-Sectional Study of Serum and Urine Fluoride in Diabetes in Fluoride Exposed Population
Sai Deepika Ram Mohan, Shashidhar Kurpad Nagaraj, Raveesha Anjanappa, Muninarayana Chandrappa
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Cystatin C predicts the risk of incident cerebrovascular disease in the elderly
Xin Zheng, Hong-da She, Qiao-xin Zhang, Tong Si, Ku-sheng Wu, Ying-xiu Xiao
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Proteinuria Is Associated with Carotid Artery Atherosclerosis in Non-Albuminuric Type 2 Diabetes: A Cross-Sectional Study
Jaehyun Bae, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee
Journal of Clinical Medicine.2020; 9(1): 136. CrossRef

Editorial

Complications
Severe Hypoglycemia and Cardiovascular Disease in Type 2 Diabetes: Hyeong Kyu Park; Diabetes Metab J. 2015;39(6):478-480. Published online December 11, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.6.478

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Citations

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Insulin-induced skin lipohypertrophies: A neglected cause of hypoglycemia in dialysed individuals with diabetes
Sandro Gentile, Ersilia Satta, Felice Strollo, Giuseppina Guarino, Carmine Romano, Teresa Della Corte, Carmelo Alfarone
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2021; 15(4): 102145. CrossRef
Insulin-Related Lipohypertrophy in Hemodialyzed Diabetic People: a Multicenter Observational Study and a Methodological Approach
Sandro Gentile, Felice Strollo, Ersilia Satta, Teresa Della Corte, Carmine Romano, Giuseppina Guarino
Diabetes Therapy.2019; 10(4): 1423. CrossRef
Postmeal increment in intact glucagon-like peptide 1 level, but not intact glucose-dependent insulinotropic polypeptide levels, is inversely associated with metabolic syndrome in patients with type 2 diabetes
Soyeon Yoo, Eun-Jin Yang, Sang Ah Lee, Gwanpyo Koh
Endocrine Research.2018; 43(1): 47. CrossRef
Myricetin: a potent approach for the treatment of type 2 diabetes as a natural class B GPCR agonist
Ying Li, Xuemin Zheng, Xiulin Yi, Changxiao Liu, Dexin Kong, Jianning Zhang, Min Gong
The FASEB Journal.2017; 31(6): 2603. CrossRef
Hypoglycemia and Health Costs
Yong-ho Lee, Gyuri Kim, Eun Seok Kang
The Journal of Korean Diabetes.2016; 17(1): 11. CrossRef

Letter

Letter: Predicting Mortality of Critically Ill Patients by Blood Glucose Levels (Diabetes Metab J 2013;37:385-90): Hyeong Kyu Park; Diabetes Metab J. 2013;37(6):484-485. Published online December 12, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.6.484

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Review

Resistin in Rodents and Humans: Hyeong Kyu Park, Rexford S. Ahima; Diabetes Metab J. 2013;37(6):404-414. Published online December 12, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.6.404

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Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resistance. However, in contrast to rodents, resistin is expressed and secreted from macrophages in humans and is increased in inflammatory conditions. Some studies have also suggested an association between increased resistin levels and insulin resistance, diabetes and cardiovascular disease. Genetic studies have provided additional evidence for a role of resistin in insulin resistance and inflammation. Resistin appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and formation of foam cells. Indeed, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. There is also growing evidence that elevated resistin is associated with the development of heart failure. This review will focus on the biology of resistin in rodents and humans, and evidence linking resistin with type 2 diabetes, atherosclerosis, and cardiovascular disease.

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Editorial

Metformin and Cancer in Type 2 Diabetes: Hyeong Kyu Park; Diabetes Metab J. 2013;37(2):113-116. Published online April 16, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.2.113

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Citations

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Metformin, Asian ethnicity and risk of prostate cancer in type 2 diabetes: a systematic review and meta-analysis
Christopher B. Chen, Maxim Eskin, Dean T. Eurich, Sumit R. Majumdar, Jeffrey A. Johnson
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Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients
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Case Reports

A Case of Multifocal Pyomyositis in Diabetes Mellitus.: Eun Seo Park, Joo Hyun Kim, Bo Yong Jung, Jae Ho Park, Ji Hun Ahn, Jun Young Lee, Soon Ho Hwang, Kyung Wook Lee, Jong Kyu Han, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo; Korean Diabetes J. 2006;30(2):140-144. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.140

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Abstract PDF: Pyomyositis is an acute bacterial infection of skeletal muscle, usually caused by Staphylococcus aureus. It is common in the tropics but rare in temperate climates. In temperature climate there are predisposing factors, such as diabetes, HIV infection, malignancy. The incidence of reported bacterial pyomyositis is increasing in recently, especially among immunocompromised persons such as HIV infection or diabetes mellitus. We experience multifocal pyomyositis in 49-year-old man with type 2 diabetes mellitus presented with drowsy mental state. Muscular USG and MRI finding shows multifocal abscess in thigh. Blood culture revealed Staphyloccus aureus. And patient received a intravenous broad-spectrum antibiotics, incision and drainage. He was successfully managed with drainage and antibiotics then discharge. Since diabetes or infection with HIV predisposes patients to bacterial infection, pyomyositis will occur more frequently. Increased awareness if the disease will improve management.

A Case of Acute Multifocal Bacterial Nephritis Associated with Diabetic Autonomic Neuropathy.: Eun Kyung Park, Jae Hak Lee, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo; Korean Diabetes J. 2003;27(4):379-384. Published online August 1, 2003

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Abstract PDF: Acute multifocal bacterial nephritis is a severe form of acute renal infection in which a heavy leukocytic infiltrate occurs throughout the kidney. It is also an early phase of renal corticomedullary abscess. Clinically, patients have evidence of a severe urinary tract infection secondary to a gram-negative organism and there are frequently signs of sepsis. About half of the reported patients have been diabetics. Urinary tract infections are more common in diabetic women than in non-diabetic women. A variety of factors may contribute. The most important predisposing factor may be bladder dysfunction as a result of diabetic neuropathy and cystopathy. Diabetic cystopathy begins as decreased bladder sensation and decreased reflex detrusor activity caused by neuropathy affecting sympathetic and parasympathetic afferent fibers. Impaired bladder sensation results in bladder distention and increased residual urine volume. Long-term effects may eventually be vesicoureteral reflux and recurrent upper urinary tract infection. However, until now no diabetic patient with acute multifocal bacterial nephritis has been reported in Korea. Acute multifocal bacterial nephritis can be diagnosed by clinical manifestations and on radiologic grounds, including abdominal computed tomography showing multiple, wedge shaped, poorly defined areas of decreased contrast enhancement in multiple renal lobes. Therefore, we report the first Korean case of acute multifocal bacterial nephritis associated with diabetic autonomic neuropathy and review the literatures.

A Case of Invasive Aspergillosis of the Nasal Septum in a Patient with Diabetes Mellitus.: Tae Hoon Kim, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo, Jang Mook Kim, Yoon Jung Kim; Korean Diabetes J. 2003;27(4):373-378. Published online August 1, 2003

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Abstract PDF: Invasive aspergillosis of the nasal cavity and paranasal sinuses is characterized by invasion and destruction of the bony sinus walls, the orbit, and other soft tissues of the face. It occurs particularly in patients with severe immune deficits, and less frequently in patients with diabetes mellitus. The therapeutic outcome of invasive aspergillosis is unsatisfactory. Mortality rates range from 50 to 80%, depending primarily on the underlying disease. In general, the prognosis depends on making a prompt diagnosis of infection and providing early treatment. However the diagnosis of invasive aspergillosis is difficult because there is no specific symptom, nor any rapid diagnostic method for confirmation. We report a case of a 64-year old woman with diabetes mellitus and invasive aspergillosis of the nasal septum. She was diagnosed by biopsy of the nasal septum and treated with systemic antifungal agent and surgical debridement. (Ed- paragraphs combined here) In conjunction with this case we review the previous literatures and suggest that prompt antifungal therapy with glycemic control is an important element in the treatment of invasive aspergillosis in a diabetic patient.

A Case of Endogenous Endophthalmitis in a Patient with Diabetic Retinopathy.: Chang Hee Han, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo, Jun Sun Kim; Korean Diabetes J. 2003;27(4):367-372. Published online August 1, 2003

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Abstract PDF: Infectious endogenous endophthalmitis can occur by entrance of a pathogenic microorganism into the eye from various primary infection sites other than the eye. Although relatively rare, it results in visual loss frequently in spite of early diagnosis and treatment. It occurs in the process of systemic infection and its underlying conditions are diabetes, advanced liver disease, and immune suppressive state or drug abuse. We report a case of a 51-year old man with proliferative diabetic retinopathy and endogenous endophthalmitis caused by S. aureus from a skin infection. The ocular symptoms improved after systemic and intravitreal antibiotic therapy but visual loss could not be prevented. In conjunction with this case, we review the available literatures and stress the seriousness of this disease when concurrent in diabetic patients.

Original Articles

Impairment of Insulin Secretion by Fat Overload in Rat Pancreatic Islets and Effects of Antioxidants.: Chul Hee Kim, Chan Hee Kim, Hyeong Kyu Park, Kyo Il Suh, Ki Up Lee; Korean Diabetes J. 2002;26(5):347-356. Published online October 1, 2002

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Abstract PDF: BACKGROUND
It has recently been suggested that fat overload on pancreatic beta cells is responsible for the abnormal pattern of insulin secretion in type 2 diabetes mellitus. Antioxidant treatment was reported to preserve beta cell function in animal models of diabetes. This study was undertaken to examine the effects of various free fatty acids and triglyceride on insulin secretion in isolated rat pancreatic islets. In addition, we examined the effects of antioxidants. METHODS: Pancreatic islets of normal Sprague-Dawley rats were isolated by intraductal injection of collagenase and Ficoll-gradient centrifugation. The islets were treated with palmitat0e (C16:0), oleate (C18:1), linoleate (C18:2), and triglyceride emulsions (intralipid) for 72hours. Basal and glucose-stimulated insulin secretions were measured. The effects of the antioxidants, vitamin E, alpha-lipoic acid, and N-acetyl cysteine, were examined on the fat-induced change of insulin secretion. RESULTS: All of the free fatty acids and the triglyceride increased the basal insulin secretion. In contrast, insulin secretion stimulated by 27 mM glucose was significantly decreased after the treatment with free fatty acids or triglycerides. The antioxidant could not prevent the fat-induced inhibition of insulin secretion. CONCLUSION: These results show that various free fatty acids and triglyceride commonly cause defects in insulin secretion. However, we could not confirm the the hypothesis that increased oxidative stress may be involved in the pathogenesis of insulin secretory defect associated with fat overload.

Effects of Hydrogen Peroxide on Insulin Secretion in Rat Pancreatic Islets.: Chul Hee Kim, Chan Hee Kim, Hyeong Kyu Park, Kyo Il Suh, Ki Up Lee; Korean Diabetes J. 2002;26(4):265-273. Published online August 1, 2002

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Abstract PDF: BACKGROUND
It has been hypothesized that reactive oxygen species (ROS) are involved in the progression of beta cell dysfunction in both type 1 and type 2 diabetes mellitus. On the other hand, recent evidence suggests that ROS might be an integral component of intracellular signaling. This study was undertaken to examine effects of hydrogen peroxide (H2O2) on insulin secretion by various secretagogues in isolated rat pancreatic islets. METHODS: Pancreatic islets from normal Sprague-Dawley rats were isolated by intraductal injection of collagenase and Ficoll-gradient centrifugation. Isolated islets were treated with H2O2 directly added to the culture media or continuously generated by glucose-glucose oxidase system for 24 hours. Insulin secretion stimulated by glucose, arginine, and KCl was measured by radioimmunoassay. RESULTS: Basal insulin secretion was increased after treatment with H2O2. Treatment with low concentration of H2O2 stimulated insulin secretion in response to 27 mM glucose. In contrast, insulin secretion stimulated by 27 mM glucose was significantly decreased after treatment with high concentrations of H2O2. Arginine- stimulated insulin secretion was increased by both low- and high concentrations of H2O2. Insulin secretion stimulated by KCl was not affected by treatment with H2O2. CONCLUSION: These results suggest that the effect of H2O2 is diverse according to its concentration and different insulin secretagogues. In particular, H2O2 has a dual action on glucose-induced insulin secretion. At low concentration, H2O2 can stimulate insulin secretion probably by acting on signaling pathway of stimulus- secretion coupling. In contrast, high concentrations of H2O2 impairs glucose- induced insulin secretion, probably by acting as an oxidative stress.

Effects of Antioxidants on Ethidium Bromide-induced Inhibition of Insulin Secretion in Rat Pancreatic Islets.: Chul Hee Kim, Chan Hee Kim, Hyeong Kyu Park, Kyo Il Suh, Ki Up Lee; Korean Diabetes J. 2002;26(3):179-187. Published online June 1, 2002

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Abstract PDF: BACKGROUND
It was recently shown that mitochondrial function in pancreatic beta-cells is essential in nutrient-stimulated insulin secretion. The inhibition of mitochondrial DNA (mtDNA) transcription by ethidium bromide (EtBr) has been reported to suppress glucose-induced insulin secretion in beta-cell lines. This study was undertaken to examine the effects of EtBr on insulin secretion in isolated normal rat pancreatic islets, and to see whether antioxidants could protect the beta-cell function against the EtBr-induced impairment. METHODS: Pancreatic islets of normal Sprague-Dawley rats were isolated by intraductal injection of collagenase followed by Ficoll-gradient centrifugation. Isolated islets were treated with 0.2 +/- 2.0 microgram/mL of EtBr for 2 to 6 days, and the glucose-stimulated insulin secretion measured. The effects of the antioxidant, vitamin E and alpha-lipoic acid, on the EtBr-induced inhibition of insulin secretion were also examined. RESULTS: EtBr inhibited the basal and glucose-stimulated insulin secretion in normal rat pancreatic islets in a dose- and time-dependent manner. Vitamin E and alpha-lipoic acid prevented the EtBr-induced inhibition of insulin secretion. CONCLUSION: Our results show that antioxidant can protect normal rat pancreatic islets from the EtBr-induced inhibition of insulin secretion. This suggests that oxidative stress is involved in the pathogenesis of the insulin secretory defect associated with mitochondrial dysfunction.

Pancreatic beta-cell Function and Development in Male Offspring of Protein-Malnourished Rats.: Hyeong Kyu Park, Cheng Ji Jin, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2002;26(1):21-30. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Nutritional deprivation of the fetus and infant may be associated with susceptibility to impaired glucose tolerance or type 2 diabetes in adult life. This association has been interpreted as a long-term effects of nutritional factors that reduce fetal growth and impair the development of tissues that regulate glucose metabolism. This study aimed to investigate the effect of protein malnutrition in a fetus and early life on the pancreatic beta-cell function and development. METHODS: Sprague-Dawley rats were fed a low-protein (8% casein) diet during pregnancy and lactation. Their male offspring were weaned onto either a control (18% casein) diet (recuperated group, R) or a low-protein diet (low-protein group, LP). The offspring of the rats fed control diet were weaned onto control diet (control group, C). Glucose tolerance tests and morphometry of the pancreas were performed to evaluate the pancreatic beta-cell function and development at the 25th week of age. RESULTS: Offspring of the protein-malnourished rats had a significantly lower body weights than the controls. The R and LP showed no major impairment in glucose tolerance, but the plasma insulin concentrations in the R (0.24+/-.03 nmol/L) and LP (0.28+/-.02 nmol/L) groups were lower at 20 min during IVGTT than the C (0.43+/-.05 nmol/L) groups. The areas under the curve for insulin (AUC insulin) during IVGTT were significantly lower in R and LP (0.39+/-.03 nmol/L/min, 0.43+/-.02 nmol/L/min) groups than the C (0.54+/-.03 nmol/L/min) group. In particular, the rats with fetal protein malnutrition showed severe impairment in late-phase insulin secretion to a glucose load. Both the pancreas weight and the proportion of the pancreas weight to the body weight were significantly lower in the R and LP groups than the C group. The proportion of beta-cells to pancreatic cells was lower in the LP (0.91+/-.14%) group than the C (2.19+/-.23%) and R (1.79+/-.25%) group. The relative beta-cell mass was significantly lower in the LP (by 62%) group that the C group. CONCLUSION: Rats with fetal protein malnutrition showed persistently impaired pancreatic beta-cell development and reduced insulin secretion capacity. These findings suggest that in utero protein malnutrition can contribute to the development of type 2 diabetes in adult life along with other deleterious environmental or genetic conditions.

Polymorphism of the Uncoupling Protein 1 (UCP-1) Gene and Fatty Acid Binding Protein 2 (FABP2) Gene in Korean Type 2 Diabetic Patients.: Sun Gyu Kim, Chul Hee Kim, Seog Ki Yun, Yeo Il Yun, Yong Hyun Kim, Il Song Nam, Ju Young Lee, Ji O Mok, Hyeong Kyu Park, Young Sun Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo; Korean Diabetes J. 2001;25(4):262-272. Published online August 1, 2001

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Abstract PDF: BACKGROUND
It is well known that genetic component plays an important role in developing obesity and type 2 diabetes mellitus. A number of candidate genes have been suggested, but the major gene determining the development of obesity and type 2 diabetes has not yet been uncovered. Previous studies suggest that polymorphisms of the intestinal fatty acid binding protein (FABP2) and uncoupling protein 1 (UCP-1) gene were related with obesity and/or insulin resistance in several populations. METHODS: We examined 76 type 2 diabetic patients (aged 44+/-6 years) and 96 healthy controls (aged 25+/-3 years). Ala54Thr polymorphism of the FABP2 gene and A to G polymorphism (-3826) of the UCP-1 gene were determined by polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: The Thr54 allele of the FABP2 gene was found with a frequency of 0.33 in nondiabetic controls and 0.36 in type 2 diabetic patients. The genotype frequency of the Ala54Thr polymorphism was similar in nondiabetic and diabetic subjects ( 2=0.87, P=0.64). The -3826 G allele of UCP-1 gene was found with a frequency of 0.51 in nondiabetic controls, and 0.46 in type 2 diabetic patients. The genotype frequency of the -3826 A to G polymorphism was also similar in nondiabetic and diabetic subjects ( 2=1.46, p=0.46). When the subjects of each groups were subdivided into nonobese and obese group by BMI of 25 kg/m2, there was no significant difference in genotype frequencies of the UCP-1 and FABP2 gene polymorphisms. CONCLUSION: These results suggest that either the Ala54Thr polymorphism of the FABP2 gene or the A to G polymorphism (-3826) of UCP-1 gene do not play a major role in developing type 2 diabetes mellitus or obesity in Korean.

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