Diabetes & Metabolism Journal

Original Article

Drug/Regimen
Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial: Ji-Yeon Park, Joonyub Lee, Yoon-Hee Choi, Kyung Wan Min, Kyung Ah Han, Kyu Jeung Ahn, Soo Lim, Young-Hyun Kim, Chul Woo Ahn, Kyung Mook Choi, Kun-Ho Yoon, the Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) study investigators; Received August 7, 2023 Accepted November 30, 2023 Published online April 23, 2024; DOI: https://doi.org/10.4093/dmj.2023.0259 [Epub ahead of print]

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Abstract PDF: Background
Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy.
Methods
The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety.
Results
After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy.
Conclusion
Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

Short Communication

Islet Studies and Transplantation
Alginate-Catechol Cross-Linking Interferes with Insulin Secretion Capacity in Isolated Murine Islet Cells: Yu-Sik Kim, Seung-Woo Cho, Bomin Ko, Jisoo Shin, Chul Woo Ahn; Diabetes Metab J. 2018;42(2):164-168. Published online March 28, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.2.164

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Over the past three decades, human pancreatic islet isolation and transplantation techniques have developed as a routine clinical procedure for selected patients with type 1 diabetes mellitus. However, due to the donor shortage and required chronic systemic immunosuppression, the widespread application of islet transplantation is limited. To overcome these limitations, providing a physical barrier to transplanted islet cells with encapsulating biomaterial has emerged as a promising approach to enhance engraftment and promote islet survival post-transplantation. Alginate has been considered to be a reliable biomaterial, as it enhances islet survival and does not hamper hormone secretion. Alginate-catechol (Al-CA) hydrogel was reported to provide high mechanical strength and chemical stability without deformation over a wide range of pH values. In this study, we, demonstrated, for the first time in the literature, that encapsulation of murine pancreatic islet cells with Al-CA hydrogel does not induce cytotoxicity ex vivo for an extended period; however, it does markedly abate glucose-stimulated insulin secretion. Catechol should not be considered as a constituent for alginate gelation for encapsulating islet cells in the application of islet transplantation.

Citations

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Alginate: Enhancement Strategies for Advanced Applications
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Alginate Functionalization for the Microencapsulation of Insulin Producing Cells
N. A. Len’shina, A. N. Konev, A. A. Baten’kin, P. S. Bardina, E. I. Cherkasova, A. V. Kashina, E. V. Zagainova, V. E. Zagainov, S. A. Chesnokov
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Original Articles

The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes: Eun Yeong Choe, Yongin Cho, Younjeong Choi, Yujung Yun, Hye Jin Wang, Obin Kwon, Byung-Wan Lee, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee, Eun Seok Kang; Diabetes Metab J. 2014;38(3):211-219. Published online June 17, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.3.211

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Abstract PDF Supplementary Material PubReader

Background

We evaluated the effects of two dipeptidyl peptidase-4 (DPP-4) inhibitors, sitagliptin and vildagliptin, on metabolic parameters in patients with type 2 diabetes mellitus.

Methods

A total of 170 type 2 diabetes patients treated with sitagliptin or vildagliptin for more than 24 weeks were selected. The patients were separated into two groups, sitagliptin (100 mg once daily, n=93) and vildagliptin (50 mg twice daily, n=77). We compared the effect of each DPP-4 inhibitor on metabolic parameters, including the fasting plasma glucose (FPG), postprandial glucose (PPG), glycated hemoglobin (HbA1c), and glycated albumin (GA) levels, and lipid parameters at baseline and after 24 weeks of treatment.

Results

The HbA1c, FPG, and GA levels were similar between the two groups at baseline, but the sitagliptin group displayed a higher PPG level (P=0.03). After 24 weeks of treatment, all of the glucose-related parameters were significantly decreased in both groups (P=0.001). The levels of total cholesterol and triglycerides were only reduced in the vildagliptin group (P=0.001), although the sitagliptin group received a larger quantity of statins than the vildagliptin group (P=0.002).The mean change in the glucose- and lipid-related parameters after 24 weeks of treatment were not significantly different between the two groups (P=not significant). Neither sitagliptin nor vildagliptin treatment was associated with a reduction in the high sensitive C-reactive protein level (P=0.714).

Conclusion

Vildagliptin and sitagliptin exert a similar effect on metabolic parameters, but vildagliptin exerts a more potent beneficial effect on lipid parameters.

Citations

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Shashank Joshi, Vathsala Jayanth, Subramanian Loganathan, Vasan K. Sambandamurthy, Sandeep N. Athalye
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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
Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis
Michał Wiciński, Karol Górski, Eryk Wódkiewicz, Maciej Walczak, Magdalena Nowaczewska, Bartosz Malinowski
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Effect of Switching from Linagliptin to Teneligliptin Dipeptidyl Peptidase-4 Inhibitors in Older Patients with Type 2 Diabetes Mellitus

Eugene Han, Minyoung Lee, Yong-ho Lee, Hye Soon Kim, Byung-wan Lee, Bong-Soo Cha, Eun Seok Kang
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 4113. CrossRef
Combined vildagliptin and memantine treatment downregulates expression of amyloid precursor protein, and total and phosphorylated tau in a rat model of combined Alzheimer’s disease and type 2 diabetes
Samar S. Khalaf, Mohamed M. Hafez, Eman T. Mehanna, Noha M. Mesbah, Dina M. Abo-Elmatty
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Therapeutic experience of saxagliptin as first add-on after metformin in Indian type 2 diabetes patients: A non-interventional, prospective, observational study (ONTARGET-INDIA)
Sanjay Kalra, Sarita Bajaj, AG Unnikrishnan, ManashP Baruah, Rakesh Sahay, V Hardik, Amit Kumar
Indian Journal of Endocrinology and Metabolism.2019; 23(3): 312. CrossRef
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Pablo F. Mora, Eric L. Johnson
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Treatment of Dyslipidemias to Prevent Cardiovascular Disease in Patients with Type 2 Diabetes
Maryam Khavandi, Francisco Duarte, Henry N. Ginsberg, Gissette Reyes-Soffer
Current Cardiology Reports.2017;[Epub] CrossRef
Sodium butyrate has context-dependent actions on dipeptidyl peptidase-4 and other metabolic parameters
Eun-Sol Lee, Dong-Sung Lee, Prakash Raj Pandeya, Youn-Chul Kim, Dae-Gil Kang, Ho-Sub Lee, Byung-Chul Oh, Dae Ho Lee
The Korean Journal of Physiology & Pharmacology.2017; 21(5): 519. CrossRef
Risk of Myopathy Associated With DPP-4 Inhibitors in Combination With Statins: A Disproportionality Analysis Using Data From the WHO and French Spontaneous Reporting Databases
Vanessa Labat, Mickael Arnaud, Ghada Miremont-Salamé, Francesco Salvo, Bernard Bégaud, Antoine Pariente
Diabetes Care.2017; 40(3): e27. CrossRef
Soluble DPP-4 up-regulates toll-like receptors and augments inflammatory reactions, which are ameliorated by vildagliptin or mannose-6-phosphate
Dong-Sung Lee, Eun-Sol Lee, Md. Morshedul Alam, Jun-Hyeog Jang, Ho-Sub Lee, Hyuncheol Oh, Youn-Chul Kim, Zahid Manzoor, Young-Sang Koh, Dae-Gil Kang, Dae Ho Lee
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Jan N. Basile
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Xiaomin Xing, Yi Han, Xiaojun Zhou, Bo Zhang, Yan Li, Zhongsu Wang, Lin Liao, Lequn Su
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Paul D. Rosenblit
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Dipeptidyl peptidase-4 inhibition and narrow-band ultraviolet-B light in psoriasis (DINUP): study protocol for a randomised controlled trial
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Efficacy of different dipeptidyl peptidase-4 (DPP-4) inhibitors on metabolic parameters in patients with type 2 diabetes undergoing dialysis
Se Hee Park, Joo Young Nam, Eugene Han, Yong-ho Lee, Byung-Wan Lee, Beom Seok Kim, Bong-Soo Cha, Chul Sik Kim, Eun Seok Kang
Medicine.2016; 95(32): e4543. CrossRef
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Elena Pavlova Filipova, Katya Hristova Uzunova, Toni Yonkov Vekov
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Mennatallah A. Ali, Hanan S. El-Abhar, Maher A. Kamel, Ahmed S. Attia, John Calvert
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The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors
Na-Hyung Kim, Taeyang Yu, Dae Ho Lee
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A Post Hoc Analysis of HbA1c, Hypoglycemia, and Weight Change Outcomes with Alogliptin vs Glipizide in Older Patients with Type 2 Diabetes
Morgan Bron, Craig Wilson, Penny Fleck
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Response: The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes (Diabetes Metab J2014;38:211-9)
EunYeong Choe, Eun Seok Kang
Diabetes & Metabolism Journal.2014; 38(4): 319. CrossRef
Letter: The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes (Diabetes Metab J2014;38:211-9)
Seung-Hwan Lee
Diabetes & Metabolism Journal.2014; 38(4): 317. CrossRef

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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Abstract PDF PubReader

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.

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Review

Diabetes Epidemics in Korea: Reappraise Nationwide Survey of Diabetes "Diabetes in Korea 2007": Ie Byung Park, Jaiyong Kim, Dae Jung Kim, Choon Hee Chung, Jee-Young Oh, Seok Won Park, Juneyoung Lee, Kyung Mook Choi, Kyung Wan Min, Jeong Hyun Park, Hyun Shik Son, Chul Woo Ahn, Hwayoung Kim, Sunhee Lee, Im Bong Lee, Injeoung Choi, Sei Hyun Baik; Diabetes Metab J. 2013;37(4):233-239. Published online August 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.4.233

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Abstract PDF PubReader

There are many studies on the prevalence, clinical characteristics, and economic burden of diabetes across the past four decades in Korea. Nonetheless, there is a dearth of nationwide study regarding diabetes encompassing all age group. Eight years ago, the Committee on the Epidemiology of Diabetes Mellitus of Korean Diabetes Association collaborated with Health Insurance Review & Assessment Service to evaluate the status of diabetes care and characteristics in diabetic patients in Korea. In 2007, the collaborative task force team published a comprehensive survey titled "Diabetes in Korea 2007." In this review, we reappraise the diabetic epidemics from the joint report and suggest further studies that are needed to be investigated in the future.

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Brief Report

Beneficial Effects of Omega-3 Fatty Acids on Low Density Lipoprotein Particle Size in Patients with Type 2 Diabetes Already under Statin Therapy: Myung Won Lee, Jeong Kyung Park, Jae Won Hong, Kwang Joon Kim, Dong Yeob Shin, Chul Woo Ahn, Young Duk Song, Hong Keun Cho, Seok Won Park, Eun Jig Lee; Diabetes Metab J. 2013;37(3):207-211. Published online June 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.3.207

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Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C), additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (≥200 mg/dL) while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL) particle size and triglyceride (TG) level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%±3.1% vs. 2.3%±3.6%, P=0.024; -41.0%±24.1% vs. -24.2%±31.9%, P=0.049). Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects.

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Original Article

Serum Cystatin C Reflects the Progress of Albuminuria: Jeong Seon Yoo, Young Mi Lee, Eun Hae Lee, Ji Woon Kim, Shin Young Lee, Ki-Cheon Jeong, Shin Ae Kang, Jong Suk Park, Joo Young Nam, Chul Woo Ahn, Young Duk Song, Kyung Rae Kim; Diabetes Metab J. 2011;35(6):602-609. Published online December 26, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.6.602

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Background

Research on the relationship between urinary albumin excretion and serum cystatin C in diabetes is restricted to cross-sectional studies. In this study, we investigated how well serial measurements of serum cystatin C level reflect changes in the urinary albumin excretion rate.

Methods

We enrolled and retrospectively collected data on 1,058 participants with type 2 diabetes who were older than 18 years and who had more than 3 years of follow-up with serial measurements of albuminuria and serum cystatin C at an outpatient clinic.

Results

With the use of a linear mixed model, we found that the albuminuria level for each patient over time corresponded with the annual change in serum cystatin C-based estimated glomerular filtration rate (cysC-eGFR) but did not correspond with the creatinine-based eGFR calculated by the modification of diet in renal disease formula (MDRD-eGFR). The discrepancy in the direction of the trend was smaller with cysC-eGFR than with MDRD-eGFR.

Conclusion

Serum cystatin C level reflects the trend in albuminuria level more accurately than serum creatinine level in Korean type 2 diabetes mellitus patients.

Citations

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Editorial

Low Density Lipoprotein Cholesterol Target Goal Attainment Rate in Korean Patients with Diabetes: Eun Hae Lee, Chul Woo Ahn; Diabetes Metab J. 2011;35(6):578-579. Published online December 26, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.6.578

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Original Article

Dietary Oleate Has Beneficial Effects on Every Step of Non-Alcoholic Fatty Liver Disease Progression in a Methionine- and Choline-Deficient Diet-Fed Animal Model: Ji Young Lee, Jae Hoon Moon, Jong Suk Park, Byung-Wan Lee, Eun Seok Kang, Chul Woo Ahn, Hyun Chul Lee, Bong Soo Cha; Diabetes Metab J. 2011;35(5):489-496. Published online October 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.5.489

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Background

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a major cause of liver-related morbidity and mortality. The underlying mechanisms of disease progression remain poorly understood, and primary therapy of NAFLD is not yet established. We investigated the effects of dietary oleate on the development and progression of NAFLD in a methionine- and choline-deficient (MCD) diet-fed animal model.

Methods

A total of 30 C57BL/6J mice were randomly divided into three groups (n=10 in each group) and fed various experimental diets for four weeks: chow, MCD diet, or OMCD (MCD diet with oleate, 0.5 mg/g/day). Liver samples were examined for steatohepatitis and fibrosis parameters and associated genes.

Results

Additional dietary oleate dramatically reduced MCD diet-induced hepatic steatosis. Hepatic carbohydrate responsive element-binding protein was overexpressed in MCD diet-fed mice, and dietary oleate prevented this overexpression (P<0.001). Dietary oleate partially prevented MCD diet-induced serum level increases in aspartate aminotransferase and alanine aminotransferase (P<0.001, respectively). The mRNA expressions of hepatic monocyte chemoattractant protein 1, tumor necrosis factor-α and matrix metalloproteinase-9 were increased in MCD diet-fed mice, and this overexpression of inflammatory molecules was prevented by dietary oleate (P<0.001). Hepatic pericellular fibrosis was observed in MCD diet-fed mice, and dietary oleate prevented this fibrosis. Altogether, dietary oleate prevented MCD diet-induced hepatic steatosis, inflammation and fibrosis.

Conclusion

Dietary oleate has beneficial effects in every step of NAFLD development and progression and could be a nutritional option for NAFLD prevention and treatment.

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Response

Response: Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus (Diabetes Metab J 2011;35:159-65): Soon Ae Kim, Woo Ho Shim, Eun Hae Lee, Young Mi Lee, Sun Hee Beom, Eun Sook Kim, Jeong Seon Yoo, Ji Sun Nam, Min Ho Cho, Jong Suk Park, Chul Woo Ahn, Kyung Rae Kim; Diabetes Metab J. 2011;35(3):300-301. Published online June 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.3.300

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Efficacy and Safety of Switching from Sitagliptin to Ipragliflozin in Obese Japanese Patients with Type 2 Diabetes Mellitus: A Single-Arm Multicenter Interventional Study
Kentaro Watanabe, Susumu Yamaguchi, Yoshinori Kosakai, Tetsuya Ioji, Hisamitsu Ishihara
Clinical Drug Investigation.2023; 43(12): 927. CrossRef

Original Article

Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus: Soon Ae Kim, Woo Ho Shim, Eun Hae Lee, Young Mi Lee, Sun Hee Beom, Eun Sook Kim, Jeong Seon Yoo, Ji Sun Nam, Min Ho Cho, Jong Suk Park, Chul Woo Ahn, Kyung Rae Kim; Diabetes Metab J. 2011;35(2):159-165. Published online April 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.2.159

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Background

Sitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects.

Methods

We obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (ΔHbA1c) and fasting plasma glucose (ΔFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in ΔHbA1c or >20% in ΔFPG levels at 24 weeks.

Results

We classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70±2.40 vs. 26.00±2.26, P≤0.01) and were younger (58.83±11.57 years vs. 62.87±12.09 years, P=0.03) than the non-responder group.

Conclusion

In Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders.

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Editorial

The Association of Brachial-Ankle Pulse Wave Velocity with Acute Postprandial Hyperglycemia in Korean Prediabetic and Diabetic Subjects: Chul Woo Ahn; Korean Diabetes J. 2010;34(5):284-286. Published online October 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.5.284

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Original Articles

Protective Effects of Lithospermic Acid B on Diabetic Nephropathy in OLETF Rats Comparing with Amlodipine and Losartan.: Eun Seok Kang, Beom Seok Kim, Chul Hoon Kim, Gi Ho Seo, Seung Jin Han, Sung Wan Chun, Kyu Yeon Hur, Chul Woo Ahn, Hunjoo Ha, Mankil Jung, Bong Soo Cha, Hyun Chul Lee; Korean Diabetes J. 2008;32(1):10-20. Published online February 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.1.10

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Abstract PDF

BACKGROUND
Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 and type 2 diabetic animal models. We examined the effects of LAB on the prevention of diabetic nephropathy compared with amlodipine, a calcium channel blocker, and losartan, an angiotensin receptor blocker, in Otsuka Long-Evans-Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS: LAB (20 mg/kg), amlodipine (10 mg/kg), or losartan (10 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks. RESULTS: None of LAB, losartan, and amlodipine exhibited effects on blood glucose levels. Treatment with amlodipine or losartan resulted in similar reductions in blood pressure; however, LAB was less effective in lowering blood pressure. Albuminuria was markedly suppressed by losartan and LAB, but not by amlodipine. LAB treatment decreased levels of renal lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta1 (TGF-beta1). CONCLUSION: These results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing oxidative stress and inflammation as potent as losartan.

Citations

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An Overview on Naturally Occurring Phytoconstituent: Lithospermic Acid
Bhupesh Chander Semwal, Amjad Hussain, Sonia Singh
The Natural Products Journal.2024;[Epub] CrossRef

Current Status of Diabetes Management in Korea Using National Health Insurance Database.: Seok Won Park, Dae Jung Kim, Kyung Wan Min, Sei Hyun Baik, Kyung Mook Choi, Ie Byung Park, Jeong Hyun Park, Hyun Shik Son, Chul Woo Ahn, Jee Young Oh, Juneyoung Lee, Choon Hee Chung, Jaiyong Kim, Hwayoung Kim; Korean Diabetes J. 2007;31(4):362-367. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.362

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BACKGROUND
The prevalence of diabetes is steadily increasing in Korea. The increase in number of people with diabetes would ultimately result in premature death, poor quality of life, and increasing economic burden. However, in our country, researches regarding on the quality of diabetes management are lacking. This study was conducted in 2005 using National Health Insurance Database to know the current status of diabetes management in Korea. METHODS: We have randomly selected 3,902 subjects out of 2,503,754 subjects who had claims with diagnosis of diabetes between January 2003 to December 2003 by using two staged cluster sampling method. Field survey with review of medical records and telephone survey was conducted with standardized record forms developed by Korean Diabetes Association; Task Force Team For Basic Statistical Study of Korean Diabetes Mellitus. RESULTS: The age of diabetic subjects was 58.1 +/- 12.6 years and the duration of diabetes was 6.2 +/- 5.5 years. Hypertension was present in 54% of diabetic subjects. Among those with hypertension, 59% were controlled with blood pressure below 140/90 mmHg, but only 19% were controlled with blood pressure below 130/80 mmHg. Hyperlipidemia was present in 29% of diabetic subjects. Only 38% of those with hyperlipidemia were controlled with LDL-cholesterol below 100 mg/dL. For glycemic control, only 40% of diabetic subjects achieved the goal of HbA1c less than 7%, which was suggested by ADA. CONCLUSION: We found that only 20~40% of diabetic subjects in Korea achieved the management goal for glucose, blood pressure, and lipids. It seems urgent to develop a quality management program for diabetes subjects in Korea.

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In vivo Corneal Confocal Microscopy and Nerve Growth Factor in Diabetic Microvascular Complications.: Ji Sun Nam, Young Jae Cho, Tae Woong Noh, Chul Sik Kim, Jong Suk Park, Min ho Cho, Hai Jin Kim, Ji Eun Yoon, Han Young Jung, Eun Seok Kang, Yu Mie Rhee, Hyung Keun Lee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2007;31(4):351-361. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.351

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Abstract PDF: BACKGROUND
In vivo corneal confocal microscopy (IVCCM) is being recognized as a non-invasive, early diagnostic tool for diabetic neuropathy, for it provides a clear image of corneal subbasal nerve plexus in detail. Nerve growth factors (NGF) are believed to regulate peripheral and central nervous system, neuronal differentiation, and regeneration of damaged nerves, and their role in diabetic neuropathy is being emphasized these days. Moreover, NGFs and receptors are also expressed in retina and renal mesangial cells, suggesting their possible role in the common pathogenesis of diabetic microvascular complications. We plan to examine corneal structures of diabetic patients and compare IVCCM with conventional tools and analyze their serum and tear NGF levels. METHODS: IVCCM, nerve conduction velocity (NCV), and serum, urine, and tear samplings were done to 42 diabetic patients. From IVCCM, we measured corneal nerve density, branch, and tortuosity, total corneal/epithelial thickness, and the number of endothelial/keratocyte cells, and we checked patients' biochemical profiles and serum and tear NGF levels. RESULTS: Patients with more severe neuropathy had less corneal endothelial cells (3105 +/- 218 vs. 2537 +/- 142 vs. 2350 +/- 73/mm3 vs. 1914 +/- 465/mm3, P = 0.02), higher serum NGF (36 +/- 15 vs. 60 +/- 57.66 vs. 80 +/- 57.63 vs. 109 +/- 60.81 pg/mL, P = 0.39) and tear NGF levels (135.00 +/- 11.94 vs. 304.29 +/- 242.44 vs. 538.50 +/- 251.92 vs. 719.50 +/- 92.63 pg/mL, P = 0.01). There was a positive correlation between neuropathy and corneal nerve tortuosity (r2 = 0.479, P = 0.044) and negative correlation between neuropathy and endothelial cell count (r2 = -0.709, P = 0.002). Interestingly, similar changes were seen in other microvascular complications as well. CONCLUSION: Our results provide a possibility of using novel tools, IVCCM and NGF, as common diagnostic tools for diabetic microvascular complications, but it should be followed by a large population study.

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