Diabetes & Metabolism Journal

Volume 24(1); February 2000

Original Articles

Mechanism of the lnsulin Secretory Defect by Chronically Elevated Glucose Leveis in Pancreatic lslets: Depletion of lnsulin Content due to Hyperstimulation by Glucose.: Yeon Ah Sung, Young Sun Hong; Korean Diabetes J. 2000;24(1):1-9. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 2 diabetes is characterized by impaired insulin secretion and decreased insulin sensitivity, although the exact relationship between these two derangements during the development of the disease has not been fully established. Hyperglycemia per se impairs insulin secretion in pancreatic B-cell and the mechanism of impaired insulin by chronic hyperglycemia could be the clue to clarify pathogenesis of type 2 diabetes, and possibly identify the treatments. This study was performed to elucidate the mechanism of impairment of glucose induced insulin secretion by chronic hyperglycemia in pancreatic islets. METHODS: Pancreatic islets were isolated from Sprague-Dawley rats. After incubation of islets in high glucose (20mM) and low glucose (5mM) media for 10 days, glucose (16.7 mM) induced insulin secretion and insulin and DNA content in the islets were measured. Then subcellular distribution of low molecular and heterotrimeric G-proteins were assessed by ADP-ribosylation and radiolabeled GTP binding. RESULTS: 1) Glucose-induced insulin secretion of the islets cultured for 10 days in high glucose media was significantly lower when compared with that in islets cultured in low glucose media (p<0,05) 2) Subcellular distributions of low and heterotrimeric G-protein was not different in the islets cultured in low glucose when compared to those cultured in high glucose. 3) lnsulin content was significantly lower in the islets cultured in high glucose media compared with that in islets cultured in low glucose media (p<0.05) 4) DNA content was not significantly different between the islets cultured in low and high glucose media, and insulin content to DNA ratio was significantly lower in the islets cultured in high glucose media compared with that in islets cultured in low glucose media (p<0.05). CONCLUSION: Impaired insulin secretion to glucose in pancreatic islets exposed to high glucose is caused by depletion of insulin stores affer hyperstimulation.

Effect of Nerve Growth Factor on Cultured Rat Schwann Cells in Hyperglycemic Condition.: Geun Young Hyung, Kyoung Hee Kim, Seung Hoon Baek, Geun Young Jang, Chung Gu Cho; Korean Diabetes J. 2000;24(1):10-18. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Nerve growth factor (NGF) is produced in tissues innervafed by its responsive neurons. In the peripheral nervous system, NGF messenger RNA (mRNA) is produced in target fields of small pain and temperature-mediating dorsal root ganglia (DRG) sensory neurons and sympathetic neurons. NGF receptors are expressed in these neurons, and NGF has been shown to promote their survival, differentiation, as well as maintenance. However, the mechanism of neuronal damage in diabetes and the effect of NGF on diabetic neuropathy are unclear. METHODS: in order to clarify the effect of hyperglycemia, the hyperglycemia-induced cytotoxic effects were evaluated by MTT assay on cultured rat Schwann cells, Schwann cells were grown with media containing concentrations of high glucose for inducing hyperglycemic condition. The neuroprotective effect of nerve growth factor (NGF) against hyperglycemia-induced Schwann cell changes were also examined. RESULT: 1. MMT50 value was at concentration of 25mM glucose after 72 hours, 2. Cell viability of cultured rat Schwann cells treated with hyperglycemic media made with 25~35mM glucose was markedly decreased in a dose-dependent manner when compared with control medium (normoglycemic medium) containing concentration of 5.5 mM glucose, While cell number did not show a dose- dependent decrease. 3. Cultured Schwann cells exposed to hyperglycemic medium made with 25mM glucose for 72 hours did nof show any morphological change as well as decrease of cell number. 4. Pretreatment of 10 ng/mL NGF for 2 hours increased remarkably the cell viability of cultured Schwann cells exposed to hyperglycemic medium(25mM glucose for 72 hours). CONCLUSIONS: The results from this study suggested that hyperglycemic condition induces the decrease of cell viability on cultured Schwann cells of rat. But it did not show the decrease of cell number and rnorphological change. The selective neurotrophic factors such as NGF are very effective in preventing dysfunction of cells induced by hyperglycemic condition.

The Combined Effects of Protein Malnutrition and Chronic Alcohol lntake on lnsulin Secretion and Sensitivity in Growing Rats.: Bong Soo Cha, Chul Woo Ahn, Hae II Lee, Yong Seok Yoon, Jae Kyeung Sung, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2000;24(1):19-36. Published online January 1, 2001

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Abstract PDF: BACKGROUND
This investigation was performed to examine the combined effects of protein malnutrition and chronic moderate amount of alcohol intake on insulin secretory capacity and sensitivity in growing rats. METHODS: Weanling 4-week-old male Sprague-Dawley rats were fed low protein [5%, (wt/wt)] or control (C, 20%) diet from 4 to 12 weeks and alcohol (5g/kg/d) or saline gavage from 8 to 12 weeks. All rats were divided into the 4 groups according to different diet protocols: group 1 (protein-deficient alcohol rats), group II (protein-deficient saline rats), group III (protein-sufficient alcohol rats), and group IV (protein-sufficient saline or control rats), At the age of 12 weeks, we determined the insulin secretory capacity and sensitivity in the 4 different diet groups. RESULTS: The results are summarized as following: 1. Normal weight gain was nearly completely arrested in protein-deficient rats compared to control rats. In protein-sufficient rats, chronic alcohol intake decreased body weight gain. Pancreatic weight adjusted with body weight was not different among the 4 groups, but epididymal fat weight adjusted with body weight was decreased in group II compared to group IV. 2. Intraperitoneal glucose tolerance was improved in group I compared to the other groups. Insulin responses to glucose challenge were markedly decreased in group II compared to group IV, but not in group l. 3. Glucose disposal rate during euglycemic clamp test was diminished in group II compared to qroup IV, but there were no differences between group I and group I 3. Glycogen synthase activities of skeletal muscle after 2 hour hyperinsulinemic state were not different among the 4 groups. 4. There were no differences of reserved insulin content of whole pancreas adjusted with pancreas weight among the 4 groups. 5. In light microscopic findings of pancreatic islets, sizes of islets, islet cells and nuclei were decreased in protein-deficlent rats compared to control rats. However, the sizes of islet cells and nuclei were further decreased in group II compared to group l. CONCLUSION: These results suggest that impaired insulin secretion and decreased insulin sensitivity due to protein malnutrition can be restored by chronic, moderate amount of alcohol intake, but these beneficial effects may not be appeared in protein-sufficient state. Therefore, the chronic alcohol intake differently influences glucose metabolism according to individual nutritional status, and further studies for the effects of alcohol intake in lean diabetic patients are required to extrapolate these resuits in human.

An Effect of Estrogen Supplementation on the Endothelium Dependent Vasodilation in Postmenopausal Women with Type 2 Diabetes Mellitus.: Jun Kim Yeo, Sang Jun Lee, In Kyu Lee; Korean Diabetes J. 2000;24(1):37-45. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although estrogen supplementation can reduce cardiovascular events in postmenopausal women, but the mechanism that mediate this beneficial effect is unclear. Thus, we investigated the acute effect of HRT on endothelial dependent vasodilation using high resolution ultrasound in healthy and diabetic postmenopausal women. METHOD: We examined endogenous (flow dependent dilatation affer 5min cuff occlusion) and exogenous (sublingual nitroglycerin) nitric oxide mediated vasodilation in the brachial artery before and after estrogen supplementation (Premarin R 0.625 mg for 1 wk) in 16 postmenopausal women, and in 18 age-matched postmenopausal women with type 2 diabetes mellitus. RESULTS: There were no differences in age, total & LDL cholesterol level, and body mass index between the groups (p>0.05). However, HDL cholesterol level was significantly lower in patient with diabetes than in normal women (1.0+/-0.3 mmol/L in diabetes and 1.4+/-0.2 mmol/L in normal, p<0.05). Basal endothelium dependent vascular reactivity was significantly attenuated in patient with diabetes when compaired with normal subjects (8.0+/-3,9% versus 13.7+/-6.2%, p<0.05). An estrogen supplementation increased endothelium dependent vasodilation not only in patient with diabetes(from 8.0+/-3.9% to 15.1+/-4.0%, p<0.05), but also in normal women (from 13.7+/-6.2% to 20.1+/-4.7%, p<0.05). Moreover the percent increase of vascular reactivity was higher in patient with diabetes(p<0,05), In contrast, the responses to sublingual nitroglycerin were comparable in diabetes (from 21.1+/-6.0% to 22.1+/-4.1%, p>0.05), and in normal women (from 25.8+/-7.8% to 25.2+/-4.5%, p>0.05) before and after estrogen supplementation. CONCLUSION: Endothelial dysfunction was prominent in patient with diabetes and it was significantly attenuated by estrogen. These results suggest that estrogen replacement improves endothelial dependent vasodilation in healthy and diabetic postmenopausal women.

Antepartum Characteristics Predicting Persistent Postpartum Glucose lntolerance in the Patients with Gestational Diabetes Mellitus (GDM).: Yoo Lee Kim, Yong Wook Cho, Seok Won Park, Seog Ki Lee, In Sup Ahn, Byung Wook Na, Jun Lee, Yun Kyung Cho, Hwa Young Lee, Sang Jong Lee; Korean Diabetes J. 2000;24(1):46-59. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The aim of this study is to investigate the prevalence of persistent postpartum glucose intolerance and to examine antepartum clinical characteri-stics for their predictability of persistent postpartum glucose intolerance in the patients with GDM. METHODS: In 211 GDM patients who showed more than two abnormal glucose values of O'Sullivan and Mahan's criteria on 100g-oral glucose tolerance test (OGTT), 75g-OGTT were performed at 6 weeks postpartum. The incidence of postpartum normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM) were investigated and antepartum ciinical parameters were compared among the three groups, Predictability of antepartum clinical characteristics for postpartum IGT and DM were also investigated by logistic regression analysis. RESULTS: When we grouped the patients into postpartum NGT, IGT, DM according to the results of 75g-OGTT performed 6 weeks postpartum, The incidence were 81,5% of subjects had NGT, 9.0% had IGT, and 9.5% had DM. Plasma glucose levels and GAUC on antepartum 100 g-OGTT(NGT: 1660+/-159, IGT: 1948+/-730, DM: 2538+/-629mmol/L ' min), and proportion of patients receiving insulin therapy increased progressively and significantly in association with worsening postpartum glucose tolerance. Frequency of positive family history of DM in qroups with IGT and DM (63,2% & 80.0%) were significantly higher than that in group with NGT(37,2%). Weight gain before diagnosis of GDM in groups with IGT and DM(6.7+/-3.9kg & 6.8+/-4.1 kg) were significantly smaller than that of group with NGT(9.5+/-3,5kg), Gestational age at diagnosis of GDM in group with DM(25.8+/-5.4 weeks) was significantly shorter than that in group with NGT(30.0+/-3,3 weeks), Proportion of subjects diagnosed earlier than 24 weeks of gestation were significantly higher in groups with IGT (15.8%) and DM (25.0%) than in group with NGT (1.2%). Proportions of subjects delivered heavier infants, > or =4 kg,were significantly higher in the DM group (40.0%) than in the NGT group (9.3%). In the patients having fasting plasma glucose levels hlgher than 5.8 mmol/L on antepartum 100g-OGTT, the prevalence of persistent glucose intolerance was significantly higher than in the patients FPG level lower than 5.8 mmol/L (61.9% vs 7.7%), Logistic regression analysis were performed using IGT and DM as the outcome of interest. The GAUC on antepartum 100g-OGTT, family history of DM, and the gestational age at diagnosis of GDM were independent predictors for both postpartum DM and postpartum IGT. CONCLUSION: The prevalence of persistent postpartum glucose intolerance in GDM patients were 18.5% and the most important independent predictor for persistent postpartum glucose intolerance was the degree of severity in glucose intolerance during pregnancy.

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.

Comparison of Clinical Characteristics of Impaired Fasting Glucose with Impaired Glucose Tolerance in Yonchon County.: In Kyong Jeong, Min Kyong Moon, Sang Wan Kim, Young Joo Park, Sun Yuk Kim, Chan Soo Shin, Do Joon Park, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Noe Kyeong Kim, Hong Kyu Lee; Korean Diabetes J. 2000;24(1):71-77. Published online January 1, 2001

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Abstract PDF: BACKGROUND
To compare the clinical characteristics of 1997 American Diabetes Association (ADA) impaired fasting glucose (IFG) based on fasting plasma glucose (FPG) with World Health Organization (WHO) impaired glucose tolerance (IGT) based on oral glucose tolerance test (OGTT) in a Korean population. METHODS: The analyses were based on the data of 2,251 subjects aged 30-80 years obtained from the surveys of Yonchon County in Korea in 1993, and the data of 1084 subjects participated in the follow-up survey in 1995. Prevalence of glucose tolerance categories was obtained by using WHO and ADA criteria, and the level of agreement was estimated by index. Cardiovascular risk profile and the incidence of diabetes based on the ADA criteria after 2 years were compared by focusing on the discordant ctiagnostic categories namely IGT/NFS in which the subjects were diagnosed as IGT by WHO criteria but normal fasting glucose(NFG) by ADA criteria and NGT/IFG diagnosed as normal glucose tolerance(NGT) by WHO but IFG by ADA. Results The ADA criteria failed to diagnose 69% of IGT patients, that is 62% of them were considered normal and 7% as diabetes. The overall agreement was poor (x statistics = 0.32, p<0.05). Subjects classified into IGT/NFG or NGT/IFG showed the worse cardiovascular risk profile and higher incidence of diabetes than NGT/NFG. Especially, subjects with NGT/IFG exhibited higher incidence of diabetes than those with IGT/NFG. CONCLUSION: Although IFG predicts subsequent development of diabetes much better than IGT, the vast majority of the subjects with IGT will be missed according to ADA criteria based on FPG only. Consequently FPG alone could be an inadequate substitute for the OGTT.

Status and Associating Factors of Complementary and Altemative Medicine Among Korean Diabetic Patients.: Yun Sook Kim, Jin Ho Chun, Jeong Hyun Park, Chang II Kang; Korean Diabetes J. 2000;24(1):78-89. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although it is not clarified the effect of complementary and alternative medicine (CAM), yet it was widely applied to the treatment of many chronic diseases. This study aimed to propose a guide for appropriate use of CAM for the treatment of diabetes mellitus in Korea. METHODS: The study subjects were 192 patients (male 93, female 99), who diagnosed with type 2 diabetes at Pusan Paik Hospital. The status and associating factors of CAM used by the patients were asked from March 1 to 31, 1999. RESULTS: The mean age of the study subjects were 57.0+/-9.6 years, and the mean duration of disease was 8.2+/-6.0 years. Approximately 71% of the subjects experience CAM at least once in past. In total, 132 kinds of CAM had been taken and the average number of CAM taken by one patient was 7.6. Silkworm was used most frequently (80.9%), then followed by ginseng (34.6%), black bean (33.1%), concoction of herbs (18.4%) and pine tree leaves (17,6%). In general, CAM was introduced by their acquaintances(64.7%), of which family relatives and friends was 51.5%, and the information about CAM were gathered from the mass media (25,0%) or health publications (20.6%). Among them, 86.8% simultaneously took CAM with the conventional therapy - diet, exercise and medication. Only 27.9% approved the effect of CAM. In logistic regression, the duration of disease (OR=1.09), contact with the mass media or health publications(OR=4.34) and education(OR=0.33) were detected as the independent factors for the use of CAM. CONCLUSION: Many diabetic patients use the various as-yet-unverified CAM without any guidelines. It is considered that there is no patient's education about CAM and the mass media and various health publications have significant impact on the spread of CAM. Therefore, to lead the appropriate use of CAM for diabetic control, it is necessary to strengthen patient's education and to filter these informations from the mass media and various health publications.

Case Report

A Case of Bartter's Syndrome occurring in Diabetes Mellitus.: Jang Yel Shin, Jeung Rae Cho, Do Young Kim, Joon Kye Lee, Chul Woo Ahn, Jae Hyun Nam, Soo Yon Nam, Young Duk Song, Kyu Hun Choi, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh, Jai Ho Han, Heun Ju Jung; Korean Diabetes J. 2000;24(1):90-96. Published online January 1, 2001

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Abstract PDF: Bartter's syndrome is characterized by hypokalemia, metabolic alkalosis, hyperreninemia and secondary hyperaldosteronism without hypertension and edema, Histologically, existing hyperplasia of the juxtaglomerular cell occurs mostly in childhood or adolescence, and initial presentation in patients over 40 years old of age is very rare. It has been recorded that Bartter's syndrome is associated with glucose intolerance, but not with overt diabetes mellitus. Whether this association is coincidental or causal is uncertain, although hypokalemia can cause glucose intolerance. We experienced a case of Bartters syndrome in 44 years old non-insulin dependent diabetic woman. She improved with potassium supplements along with combination of prostaglandin synthetase inhibitor and aldosterona antagonist. We report present case with the review of literature.

Original Article

An Autopsy Case of Diabetes Mellitus with Extensive Atherosclerotic Complication.: Seok Hyung Kim, Jeong Wook Seo, In Ae Park, Seong Hoe Park, Eui Keun Ham, Hyun Soon Lee; Korean Diabetes J. 2000;24(1):97-101. Published online January 1, 2001

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Abstract PDF: BACKGROUND
A variety of circulatory abnormalities including atherosclerosis is a major complication of diabetes mellitus. In contrast to Western countries, incidence of extensive atherosclerotic complication is thought to be very low in Korean diabetic patients. METHODS: Recently, we have experienced an autopsy case of 66-year-old male with type 2 diabetes mellitus having severe atherosclerosis in major arteriss. RESULTS: Autopsy examination revealed severe ulcerative atherosclerosis in aorta and atheromatous embolization in numerous small and medium sized arteries of lung, kidney, liver, and intestine. Multiple old infarcts were noticed in myocardium and brain. In addition, severe diabetic nephropathy and pyelonephritis were also observed in kidneys. CONCLUSION: The cause of death in this case is assumed to be myocaridial infarction associated with obstruction of coronary arteries. This case suggests that incidence of extensive atherosclerosis in Korean diabetic patients may not be rare, if autopsy examination are performed more thoroughly on these patients.

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