Diabetes & Metabolism Journal

Original Article

Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats: Jae Hee Ahn, Ho Cheol Hong, Myong Jin Cho, Yoon Jung Kim, Hae Yoon Choi, Chai Ryoung Eun, Sae Jeong Yang, Hye Jin Yoo, Hee Young Kim, Ji A Seo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Nan Hee Kim; Diabetes Metab J. 2012;36(2):128-135. Published online April 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.2.128

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Background

Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats.

Methods

Animals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks.

Results

Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-β1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups.

Conclusion

Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug.

Citations

Citations to this article as recorded by

Up-Date on Diabetic Nephropathy
Maria Chiara Pelle, Michele Provenzano, Marco Busutti, Clara Valentina Porcu, Isabella Zaffina, Lucia Stanga, Franco Arturi
Life.2022; 12(8): 1202. CrossRef
The role of free radical oxidation in the kidneys in the nephroprotective action of eplerenone, a mineralocorticoid receptor antagonist, in experimental diabetes mellitus
A. Yu. Zharikov, S. O. Filinova, O. N. Mazko, O. G. Makarova, I. P. Bobrov, V. M. Bryukhanov
Bulletin of Siberian Medicine.2021; 20(2): 29. CrossRef
Effect of Mineralocorticoid Receptor Antagonism and ACE Inhibition on Angiotensin Profiles in Diabetic Kidney Disease: An Exploratory Study
Johannes J. Kovarik, Christopher C. Kaltenecker, Oliver Domenig, Marlies Antlanger, Marko Poglitsch, Chantal Kopecky, Marcus D. Säemann
Diabetes Therapy.2021; 12(9): 2485. CrossRef
Diabetic nephropathy: An update on pathogenesis and drug development
Vikram Rao A/L B Vasanth Rao, Sean Hong Tan, Mayuren Candasamy, Subrat Kumar Bhattamisra
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2019; 13(1): 754. CrossRef
Effects of mineralocorticoid receptor antagonists on the progression of diabetic nephropathy
Li‐Jing Sun, Yan‐Ni Sun, Jian‐Ping Shan, Geng‐Ru Jiang
Journal of Diabetes Investigation.2017; 8(4): 609. CrossRef
New agents modulating the renin-angiotensin-aldosterone system—Will there be a new therapeutic option?
Anna Gromotowicz-Poplawska, Piotr Szoka, Patrycjusz Kolodziejczyk, Karol Kramkowski, Marzena Wojewodzka-Zelezniakowicz, Ewa Chabielska
Experimental Biology and Medicine.2016; 241(17): 1888. CrossRef
Crosstalk between peroxisome proliferator-activated receptor-γ and mineralcorticoid receptor in TNF-α activated renal tubular cell
Jing Xiao, Weijun Chen, Yijun Lu, Xiaoli Zhang, Chensheng Fu, Zhenwen Yan, Zhenxing Zhang, Zhibin Ye
Inflammation Research.2015; 64(8): 603. CrossRef
Eplerenone reduces arterial thrombosis in diabetic rats
Agnieszka Zakrzeska, Anna Gromotowicz-Popławska, Janusz Szemraj, Piotr Szoka, Wioleta Kisiel, Tomasz Purta, Irena Kasacka, Ewa Chabielska
Journal of the Renin-Angiotensin-Aldosterone System.2015; 16(4): 1085. CrossRef
Pharmacological modulation of fibrinolytic response – In vivo and in vitro studies
Karol Kramkowski, Agnieszka Leszczynska, Wlodzimierz Buczko
Pharmacological Reports.2015; 67(4): 695. CrossRef

Case Reports

A Case of Cured Diabetes Mellitus after Occult Malignant Pheochromocytoma Removal.: Ho Chan Cho, Hye Soon Kim, Yoon Jung Kim, Yu Jin Hah, Nam Keong Kim, Mi Kyung Kim, Keun Gyu Park, Yong Hoon Kim, Sun Young Kwon; Korean Diabetes J. 2007;31(6):520-524. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.520

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Abstract PDF

Pheochromocytoma is characterized by a combination of various clinical manifestations that include the classic triad of severe headache, palpitations and diaphoresis. In addition, hyperglycemia can be caused by overproduction of catecholamines, which are secreted by a catecholamine-secreting neoplasm of adrenal or extra-adrenal chromaffin tissue. We encountered a case of diabetes with an occult malignant adrenal pheochromocytoma, who did not have any classic manifestations. A 37-year-old male was admitted because of polydipsia, polyuria, and weight loss. Fasting blood glucose level was 497 mg/dL, hemoglobin A1c level was 15%, and diabetic retinopathy and peripheral polyneuropathy were also accompanied. Incidentally, right adrenal mass was detected by ultrasonography of abdomen. Urinary excretion of total metanephrine and epinephrine were elevated. Adrenal CT showed a 7.1 cm sized right adrenal cystic mass with enhancing solid portion and hemorrhagic content. The scan with 123I-MIBG revealed the cystic mass with increased rim uptake in the region of right adrenal gland. After removal of the tumor, the increased levels of catecholamine were normalized. Moreover, blood glucose level was normalized without administration of insulin or oral hypoglycemic agents. The pathologic examination showed that the neoplasm was a malignant adrenal pheochromocytoma. We report this case that diabetes was cured after removal of malignant tumor with literature review at first in Korea.

Citations

Citations to this article as recorded by

Pheochromocytoma with Markedly Abnormal Liver Function Tests and Severe Leukocytosis
Chai Ryoung Eun, Jae Hee Ahn, Ji A Seo, Nan Hee Kim
Endocrinology and Metabolism.2014; 29(1): 83. CrossRef

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.

Original Article

Microvascular Complications and lts Relationship with Obesity in Outpatient Type 2 Diabetics.: Seong Kyu Lee, Bong Nam Chae, Eun Gyoung Hong, Hye Lim Noh, Hyeon Kyoung Cho, Yoon Jung Kim, Mi Deok Lee, Yoon Sok Chung, Kwan Woo Lee, Nam Han Cho, Hyeon Man Kim; Korean Diabetes J. 2000;24(1):60-70. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Korean type 2 diabetic patients who are frequently non-obese, may be genetically different from Western type 2 diabetics who are frequently obese. Therefore, the diabetic complications of type 2 diabetes mellitus in Korea may be also different from those of Western countries. Until now, most studies reported in Korea did not analyse the microvascular complications of type 2 diabetes mellitus according to obesity, and also the criteria in the diagnosis of microvascular complications were different in each study. We investigated the microvascular complications and its relationship with obesity, in type 2 diabetic patients visiting an outpatient clinic. METHODS: The study subjects were type 2 diabetic patients visiting an outpatient clinic of Ajou University Hospital. We selected patients participating in a 75 g oral glucose tolerance test, retrospectively. Type 2 diabetes was diagnosed according to the WHO/NDDG classification of diabetes. Biochemical studies including lipid profile, plasma insulin and C-peptide levels were done. Anthropometric measurements were performed. Based on BMI (kg/m2), the patients were divided into the following groups: the lean group, whan the BMI was less than 20kg/m2; the ideal body weight (IBW) group, if the BMI was between 20 kg/m and 25 kg/m in women and 20kg/m and 27 kg/m in men; and the obese group, when the BMI was>25 kg/m in women and >27 kg/m2 in men. RESULTS: 1. Neuropathy (45.2%) was the most frequent among the microvascular complications, and the frequency of retinopathy was 15.1%, and that of nephropathy was 4.9k. Within 5 years of diabetes duration, the frequency of neuropathy, retinopathy, and nephropathy was 43.2%, 11.8%, and 2,9%, respectively. 2. Glycosylated hemoglobin (HbA1c) and fasting blood glucose levels were not different among the three groups. Beta cell function{delta(insulin 30min insulin Omin)/delta(glucose 30min - glucose Omin)} was the highest in the obese group, However, beta cell function(delta/delta G) divided by the basal insulin level, considered insulin resistance, was not different among the three groups. 3. Within 5 years of diabetes duration, retinopathy tended to be the most frequent in the lean group, whereas neuropathy tended to be the most frequent in the obese group, and body mass index influenced the retinopathy and neuropathy, statistically significantly. CONCLUSION: Diabetic neuropathy was the most frequent among microvascular complications of type 2 diabetes mellitus in our study subjects. At the time of presentation within 5 years of diabetes duration, the lean group of type 2 diabetics had a tendency of the more frequent retinopathy, the obese group had a tendency of the more frequent neuropathy. These results suggest that type 2 diabetes mellitus in Korea is also not a singie disease entity, as in Western countries and is a heterogenous group of disorders with a diversity of microvascular complications. However, the more studies about this will be required.

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