Diabetes & Metabolism Journal

Volume 27(4); August 2003

Review

Diabetes Mellitus in Elderly Korean.: Sei Hyun Baik, Kyung Mook Choi; Korean Diabetes J. 2003;27(4):299-303. Published online August 1, 2003

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Editorial

Potential Role of Leptin Resistance in Metabolic Syndrome.: Seong Min Han, Joong Yeol Park; Korean Diabetes J. 2003;27(4):304-312. Published online August 1, 2003

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Original Articles

Association between Hyperleptinemia and Metabolic Syndrome in an Urban Korean Community.: Jee Young Oh, Young Sun Hong, Yeon Ah Sung; Korean Diabetes J. 2003;27(4):313-322. Published online August 1, 2003

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Abstract PDF: BACKGROUND
To determine whether hyperleptinemia is a principal component of metabolic syndrome in a Korean population using factor analysis. METHODS: Metabolic syndrome was defined by the NCEP-ATP III guideline. An oral glucose tolerance test was performed, and plasma samples for leptin and lipid profiles were collected from 199 men and 426 women who had no history of diabetes, hypertension, dyslipidemia, or of taking lipid-lowering, antihypertensive, or antihyperglycemic medications. RESULTS: Leptin level was correlated with overall and central obesity, blood pressure, and glucose or insulin levels in men and women aged 30 to 83. Before and after adjustment for BMI, leptin level was significantly and positively correlated, in women only, with insulin and with insulin resistance, as assessed by a homeostasis model assessment (HOMA) (Ps<0.0001). Factor analysis identified the following four factors from among the metabolic syndrome variables; an obesity/hyperinsulinemia factor, a glucose intolerance factor, a hypertension factor, and a dyslipidemia factor in men. Leptin was clustered as an obesity/ hyperinsulinemia and a dyslipidemia factor in men. In women, four different groups were found: an obesity/hypertension factor, a glucose intolerance factor, an obesity/dyslipidemia factor, and an obesity/hyperinsulinemia factor. Leptin was clustered as an obesity/hyperinsulinemia factor in women. CONCLUSION: Our research suggests that leptin level is associated with metabolic syndrome in relation to obesity and hyperinsulinemia. Moreover, obesity, as opposed to hyperinsulinemia, is related to hypertension or dyslipidemia in women only, and this gender differences may reflect different roles of central adiposity on metabolic abnormalities.

Effect and Mechanism of High Glucose Level on the Expression of an Adhesion Protein, beta ig-h3, and Cellular Function in Endothelial Cells.: Sung Woo Ha, Hye Jin Yeo, Jong Sup Bae, Sung Chang Chung, Jung Guk Kim, In San Kim, In Kyu Lee, Bo Wan Kim; Korean Diabetes J. 2003;27(4):323-331. Published online August 1, 2003

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Abstract PDF: BACKGROUND
Diabetes mellitus is a high risk condition for the development of atherosclerotic and thromboembolic macroangiopathy. There are many factors which are involved in development of these processes. Given the central pathogenic role of endotheliopathy in atherosclerosis, it is likely that this vascular monolayer is the ultimate target of injury in response to many cytokines and growth factors. A dysfunctional endothelium may contribute to the proatherogenic environment. Transforming growth factor (TGF-beta) is a key factor in the development of diabetic angiopathy and atherosclerosis because of its effect on the accumulation of extracellular matrix proteins and endothelial function. The adhesive molecule betaig-h3 is an extracellular matrix protein whose expression is induced by TGF-beta. Considering that TGF-beta plays an important role in diabetic complications and that betaig-h3 is a downstream target gene of TGF-beta, we hypothesized that betaig-h3 may also play a role in the development of diabetic angiopathy through its effect on the endothelial function. Therefore, we examined the effects of high glucose level on the expression of betaig-h3 and endothelial function in human umbilical vein endothelial cells (HUVECs). We also studied the mechanisms of this high glucose-induced betaig-h3 expression. METHODS: Endothelial cells were isolated from human umbilical cord and conditioned with different concentrations of TGF-beta or glucose. We measured TGF-beta and betaig-h3 protein presence/concentration/expression in cell supernatant by ELISA and examined whether TGF-beta is involved in high glucose-induced betaig-h3 expression. Finally, we investigated the biologic function of betaig-h3 in endothelial cells by using adhesion assay. RESULTS: Our study demonstrated that both high glucose level and TGF-beta induced betaig-h3 protein expression in HUVECs. High glucose level also induced TGF-beta protein expression in cells. Anti-TGF-beta antibody almost completely blocked high glucose-induced betaig-h3 expression. betaig-h3 was found to support the adhesion of endothelial cells. CONCLUSION: These results suggest that high glucose level upregulates betaig-h3 protein levels through the induction of TGF-beta and that betaig-h3 may play an important role in diabetic angiopathy by regulating adhesive function of endothelial cells.

A Differential Effect of Intracellular ATP on Skeletal-and Smooth Muscle-Type KATP Channel Activities.: Oh Dae Kwon, Jeong Geun Lim, Haeng Gyun Kim, Dae Kwang Kim, Jae Seok Hwang, Keun Gyu Park, Sung Hee Park, Chi Heum Cho, In Kyu Lee, Dae Kyu Song; Korean Diabetes J. 2003;27(4):332-342. Published online August 1, 2003

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Abstract PDF: BACKGROUND
The ATP-sensitive potassium (KATP) channel comprises an inwardly- rectifying K+ channel (Kir) and a sulfonylurea receptor(SUR). This study investigated the mechanism of different ATP sensitivity between skeletal-(Kir6.2/SUR2A) and smooth muscle- (Kir6.2/SUR2B) type KATP channels. METHODS: Messenger RNAs encoding mouse Kir6.2, and rat SUR2A or 2B were co-injected into Xenopus Laevis oocytes to express each type of KATP channel. Using the inside-out patch clamp technique, the channel currents for MgATP sensitivity were measured and analyzed. RESULTS: By addition of 100 microM of MgATP, the current initially decreased and then slowly increased in Kir6.2/SUR2A. This gradual, ATP sensitivity decrease during prolonged MgATP application was totally blocked by LY 294002, a pho- sphatidylinositol-3 and -4 kinase inhibitor. In contrast, a rather rapid sensitivity decrease after initial inhibition was observed in Kir6.2/SUR2B by 100 microM of ATP, which was not blocked by LY 294002. This channel activation was Mg2+- dependent, suggesting that ATP hydrolysis is critical. CONCLUSION: This result supports the idea that the ability of MgATP to stimulate Kir6.2/SUR2B channels reflects a faster rate of ATP hydrolysis at NBD2 of SUR2B.

Mechanism of Podocyte Injury in Diabetic Nephropathy.: Eun Young Lee, Jae sook Song, Choon Hee Chung, Sae Yong Hong; Korean Diabetes J. 2003;27(4):343-351. Published online August 1, 2003

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Abstract PDF: BACKGROUND
Since podocytes are involved in the maintenance of filtration barrier and normal structure in the kidney, podocyte injury can cause the disturbance of glomerular permselectivity and resultant proteinuria, and recent evidence shows that podocyte injury is associated with oxidative stress. However, the pathogenetic mechanism of podocyte injury in the development of diabetic nephropathy is not known. Thus, the present study examined the effect of high glucose level on cytoskeleton, slit diaphragm, podocyte-glomerular basement membrane interaction, and oxidative stress in cultured podocytes. METHODS: Differentiated cultured podocytes were used in this study. Quiescent cells were incubated with culture media containing 30 mM glucose for 48 hours. The amounts of integrin alpha3, vinculin, zona occludens (ZO)-1 and fibronectin protein expressed by podocytes were measured by Western blot analysis. Dichlorofluorescein diacetate-sensitive intracellular reactive oxygen species (ROS) were observed by confocal microscope and quantified by quantification software. Thiobarbituric acid reactive substances were also measured. Podocytes incubated with culture media containing 5.6 mM glucose were used as control. RESULTS: Integrin alpha3 expression was significantly decreased in podocytes cultured under high glucose level compared to control. However, vinculin and ZO-1 expressions were significantly increased in podocytes cultured under high glucose level compared to control. Fibronectin protein secreted by podocytes was also increased in podocytes cultured under high glucose level compared to control. ROS and thiobarbituric acid reactive substances in podocytes were also increased in high glucose medium compared to control. CONCLUSION: High glucose-induced oxidative stress and the changes of integrin a3, ZO-1 and vinculin lead to the alterations of cytoskeleton, intercellular or cell-matrix interactions. This podocyte injury may play a major role in the disturbance of the urinary filtration barrier and the development of proteinuria. These results confirmed the important role of podocyte injury in the development of diabetic nephropathy.

Relations between Insulin Resistance and Hematologic Parameters in Elderly Koreans: Southwest Seoul (SWS) Study.: Kye Won Lee, Hye Jin Yoo, Soo Yeon Park, Ohk Hyun Ryu, Sang Soo Park, Soon Beom Kwon, Hee Young Kim, Ji A Seo, Jeong Heon Oh, Dong Hyun Shin, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Hyoung Jin Kim; Korean Diabetes J. 2003;27(4):352-361. Published online August 1, 2003

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Abstract PDF: BACKGROUND
The clustering of cardiovascular risk factors is known as insulin resistance syndrome. Hyperinsulinemia has been suggested as a cardiovascular risk factor due to the capacity of insulin to induce vascular endothelial proliferation and atherosclerosis. Insulin also has been shown to stimulate erythroid colony formation independently of erythropoietin. WBC count is one of the major components of the inflammatory process and is increased by IL-6, which is high in those with features of insulin resistance. In this study, we investigated whether insulin resistance affects hematological parameters. METHODS: In this study, 1,314, randomly selected, non-diabetic, elderly subjects over 60 years living in the southwest area of Seoul were recruited. Subjects underwent 75 g OGTT and careful physical examinations during evaluation, and were interviewed using a standardized questionnaire. Biochemical data and hematologic parameters were also measured. Insulin resistance was calculated by HOMA (homeostasis model assessment) method. Analysis of variance, Duncan's multiple comparisons and multiple linear regression analysis were carried out. RESULTS: In the male non-smoking group we found a correlation between insulin resistance and hemoglobin concentration (r=0.20, p=0.0186). In the female non- smoking group we found correlations between insulin resistance and both hemoglobin concentration (r=0.10, p=0.0017) and white blood cell (WBC) count (r=0.15, p=0.001). Hemoglobin concentration and WBC count were also correlated with BMI, systolic and diastolic blood pressure, lipid profiles and fasting insulin levels in female non-smokers. In multiple regression analysis, using HOMA IR as a dependent variable, we found significance in the variables of hemoglobin concentration, WBC count, age, BMI and triglyceride level. CONCLUSION: Our study provided evidence for a relation between insulin resistance and hematological parameters such as hemoglobin concentration and WBC count in elderly Koreans. This suggests that increased hemoglobin level and WBC count could be considered as novel aspects of the met.

Case Reports

Hemichorea Associated with Type II Diabetes Mellitus.: Ju Hee Maeng, Hee Sup Lee, Jin Gun Jang, Bae Gun Park, Kwang Deog Jo, Myoung Sook Shim, Jin Yub Kim; Korean Diabetes J. 2003;27(4):362-366. Published online August 1, 2003

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Abstract PDF: Hemichorea has been reported as a rare complication of nonketotic hyperglycemia. We report a diabetic patient who developed paroxysmal hemichorea. When hyperglycemia is corrected, the movement disorder resolves within a few days. The MR images showed high signal intensity on T1-weighted images and low signal intensity on T2-weighted images in the left basal ganglia contralateral to the involuntary movement. We present a case of hemichorea in a poorly controlled 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.

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 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.

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