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Volume 25(2); April 2001
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Review
Insulin Gene Therapy.
Hyun Chul Lee, Do Min Kim
Korean Diabetes J. 2001;25(2):103-109.   Published online April 1, 2001
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  • 19 Download
AbstractAbstract PDF
No abstract available.
Editorial
Pathophysilolgy and Epidemiology of Diabetes in Elderly.
Chan Soo Shin
Korean Diabetes J. 2001;25(2):110-112.   Published online April 1, 2001
  • 1,056 View
  • 20 Download
AbstractAbstract PDF
No abstract available.
Original Articles
Serum Proinsulin, Proinsulin/Total Insulin Ratio and Insulin Resistance in Elderly-onset Type 2 Diabetes.
Yoon Ju Oh, Young Ju Park, Young Wan Kim, Sung Ki Kim, Seong Bin Hong, Yoe Joo Kim, Mi Rim Kim, Moon Suk Nam, Yong Seong Kim
Korean Diabetes J. 2001;25(2):113-124.   Published online April 1, 2001
  • 1,097 View
  • 18 Download
AbstractAbstract PDF
BACKGROUND
It is well known that the concentration of serum proinsulin and the ratio of proinsulin/total insulin (P/I) are elevated in type 2 diabetes. Proinsulin is produced by the ribosome in pancreatic beta cells, undergoes maturation in Golgi body and exists in the form of secretory granules. Immature granules possess disproportionately large amount of proinsulin. When there is increased demand of insulin caused by diabetes, higher level of proinsulin is secreted from immature granules of dysfunctioning beta cells. Thus, the elevated concentration of proinsulin and the increased ratio of P/I are considered to be the markers of pancreatic dysfunction and predictors for the future development of diabetes. The elderly-onset type 2 diabetes is also thought to develop due to both dysfunction of insulin secretion by impaired beta cell with aging and increased insulin resistance in peripheral tissue due to less muscle mass and more fat. However, it is still controversial as to which mechanism is predominant in the development of type 2 diabetes. METHODS: We measured the levels of fasting blood glucose, serum proinsulin and specific human insulin by using radioimmunoassay kit, and calculated the P/I ratio and insulin sensitivity index in normal adults (40or=60, n=35) and also in the newly-diagnosed elderly type 2 diabetes (age>or=60, n=24). RESULTS: The concentration of serum proinsulin and the ratio of P/I in normal adults over age 40 were 7.70+/-6.08 pmol/L and 0.13+/-0.10, respectively. The concentration of proinsulin in the normal adult, normal elderly and elderly diabetes group were 6.50+/-3.71, 11.17+/-8.30 and 16.75+/-11.68 pmol/L. The differences among three groups were statistically significant (p= 0.0001). The P/I ratios for each of the three groups were 0.11+/-0.05, 0.17+/-0.12 and 0.16+/-0.08 (p=0.0004). P/I ratios in the elderly control and elderly diabetes were higher than that of the normal adult group. Insulin sensitivity index (ISI, 10,000/(basal glucose X basal insulin)) of elderly diabetes (1.19+/-0.89) was lower when compared with the indices of other groups (40or=60 control; 2.27+/-1.11, p=0.0001). CONCLUSION: Although the age-related reduction of pancreatic insulin secretory function attributes to the pathogenesis of old-age onset type 2 diabetes, it appears that the decreased insulin sensitivity may serve as more important factor in the development of the disease.
Prevalence of Diabetes mellitus in Elderly Korean in Southwest Seoul (SWS Study): Comparision of 1997 ADA and 1985 WHO Criteria in Elderly Korean.
Sei Hyun Baik, Kyung Mook Choi, Young Jik Cho, Kyung Oh Kim, Dong Rim Kim, Nan Hee Kim, Shin Gon Kim, Dong Hyun Shin, Ie Byung Park, Dong Seop Choi
Korean Diabetes J. 2001;25(2):125-132.   Published online April 1, 2001
  • 1,140 View
  • 24 Download
AbstractAbstract PDF
BACKGROUND
The prevalence of diabetes in Korea is increasing rapidly, however we do not have much reliable data to prove it. Thus, the Southwest Seoul Study (SWS Study) designed to investigate the prevalence of diabetes (Clinical impact of new diagnostic criteria of ADA compare to the one of WHO), other metabolic diseases, and the proportion of diabetes related mortalities in the elderly Korean southwest Seoul population in prospectively. However, in this report we summarized the prevalence of diabetes only. METHODS: Randomly selected 1,737 elderly subjects over 60 years who lived in southwest area of Seoul were recruited in this study. Subjects underwent 75 gOGTT, interviewed using the standardized questionnaire, and careful physical examinations during the evaluation. Biochemical data were collected from 1,652 subjects and were analysed for this report. Of 1,652 subjects, we identified 196 pre-diabetics. However, these subjects were included in this analysis. ADA criteria [FBS>or=126 mg/dL (7.0 mmol/L)] and WHO criteria [75 gOGTT, pp2h >or= 200 mg/dL (11.1 mmol/L)] were used as the criteria for diagnosis of diabetes. ADA and WHO criteria for impaired glucose tolerance [IGT, WHO: FBS<7.0 mmol/L, 7.8 mmol/L
Dissociation of Microangiopathy and Macroangiopathy in Patients with Type 2 Diabetes.
C J Seo, K Y Lee, K S Song, Y S Jung, Hong Kyu Kim, H Y Park, W G Lee, M H Kang
Korean Diabetes J. 2001;25(2):133-141.   Published online April 1, 2001
  • 1,117 View
  • 45 Download
AbstractAbstract PDF
BACKGROUND
Type 2 diabetes is a heterogeneous disease. As to its complications, microangiopathy predominantly develop in some patients while macroangiopathy is more predominant in others. Therefore, this study was performed to identify the factors associated with such dissociation. METHODS: Type 2 diabetic patients were classified into the macro and microangiopathy groups by carotid intima-medial thickness (IMT) and the presence of severe diabetic retinopathy. Patients with IMT
Relationship Between Intimal-Medial Thickness (IMT) of the Carotid Artery and Atherosclerotic Risk Factors in Patients with type 2 Diabets Mellitus.
Yu Bae Ahn, So Lyung Jung, Seung Hyun Ko, Ki Ho Song, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2001;25(2):142-151.   Published online April 1, 2001
  • 1,137 View
  • 20 Download
AbstractAbstract PDF
BACKGROUND
Diabetes mellitus is a major independent risk factor for atherosclerosis. In recent years non-invasive high resolution B-mode ultrasound methods have been developed to measure the IMT (intima-media thickness) of the carotid artery as an index for early atherosclerosis. The aims of this study were to measure IMT in type 2 diabetic patients, to investigate the relation of various cardiovascular risk factors to IMT, and to evaluate the difference in IMT according to presence of diabetic complication. METHODS: IMT was measured by ultrasound B-mode imaging in 300 subjects with type 2 diabetes mellitus (131 male, 169 female adults aged 53.4+/-9.5 years, duration of diabetes 7.4+/-6.3 years). All subjects underwent coronary artery disease (CAD) risk factors assessment and the presence of diabetic complications were evaluated. RESULT: There were positive correlations between IMT and age, duration of diabetes, LDL-C, systolic blood pressure and Lp (a) level. Multiple linear regression analysis demonstrated that in type 2 diabetic patients, the variables that interact independently with IMT were age, systolic blood pressure, levels of total cholesterol, HDL cholesterol and sex. IMT was significantly increased in type 2 diabetic patients with macrovascular complication regardless of presence of microvascular complication. But there was no significant difference in IMT according to Lp (a) level, presence of microalbuminuria, mode of treatment and glycemic control. CONCLUSION: The Intima-Media thickness of patients with type 2 diabetes mellitus was associated with age, systolic blood pressure, levels of total cholesterol, HDL-C and sex.
Effect of Probucol on the Apoptosis of Pancreatic Islet Cells in Multiple Low Dose Streptozotocin Induced Diabetic (LDSD) Mice.
Kyung Mook Choi, Dong Rim Kim, Nan Hee Kim, Chul Hwan Kim, Sei Hyun Baik, Dong Seop Choi
Korean Diabetes J. 2001;25(2):152-163.   Published online April 1, 2001
  • 1,004 View
  • 18 Download
AbstractAbstract PDF
BACKGROUND
Type 1 Diabetes Mellitus(DM) is consequence of pancreatic beta cell destruction by immune interactions of auto-reactive T cells and cytokines. In individuals with genetic predisposition, an environmental insult triggers immune reaction against beta cells to produce clinical type 1 DM. Since the capacity to form new beta cells from precursors and power of replication appear to be limited, the susceptibility of beta cell to death may be the major underlying variable influencing the occurrence of type 1 DM. However, the precise mechanism of beta cell death is not known. Apoptosis is a physiologic form of cell death and recent studies reported that it could play an important role in beta cell death in experimental diabetic animal models such as multiple low dose streptozotocin diabetic (LDSD) mice or non- obese diabetic (NOD) mice. Probucol is a hypocholesterolemic agent with antioxidant properties. Some studies reported that the probucol could reduce the blood glucose level in type 1 animal models but the mechanism was not known. Therefore, this study was performed to define whether the probucol could decrease the degree of hyperglycemia and the mechanism of its attenuation on the severity of pancreatic insulitis by reducing the degree of apoptosis in LDSD mice. METHODS: We performed an experimental study with male Charles-River CD-1 mice. Mice were divided into the 30 streptozotocin-induced diabetics, 30 probucol- treated streptozotocin-induced diabetics. At 1, 5, 10, 15, and 20 days after streptozotocin administration, the blood glucose level was measured and mice were sacrificed to determine the grade of insulitis and apoptosis. The numbers of apoptotic cells of pancreatic islets were compared using double staining immunohistochemical method (TUNEL and insulin antibody staining). RESULTS: The level of blood glucose and the severity of insulitis were decreased in the probucol treated LDSD mice group significantly when compared with the control LDSD mice group. The numbers of apoptotic cells of pancreatic islets were decreased in the probucol group. The appearance of apoptosis of beta cells preceded the development of insulitis in LDSD mice. CONCLUSION: Probucol can reduce blood glucose level and the severity of insulitis by the decrease of apoptosis in LDSD mice.
Selective beta-Cell Loss and alpha-Cell Expansion in Islets of Type 2 Diabetic Patients.
Jae Hyoung Cho, In Kyu Lee, Kun Ho Yoon, Seung Hyun Ko, Sun Hee Suh, Jung Min Lee, Sung Rae Kim, Yoo Bae Ahn, Jong Min Lee, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2001;25(2):164-177.   Published online April 1, 2001
  • 1,471 View
  • 28 Download
AbstractAbstract PDF
BACKGROUND
It has been reported that a decrease in the beta-cell mass, may play a major role in the development of type 2 diabetes. Some stimuli that cause beta-cell loss can stimulate neogenesis from precursors as well as replication of matured beta-cells. In an animal-based studies reported that alpha-cells can also be produced in the course of alpha-cell neogenesis, after being treated with streptozotocin. Through this research, we attempted to determine the change of beta-cell mass according to the changes in alpha-cell mass and to characterize the size of the beta-cell nucleus observed in type 2 diabetes. METHOD: To estimate the relative fraction of alpha- and beta-cell mass in the pancreas, we counted beta-cells and alpha-cells by point count method. We also performed a double immunohistochemical staining with glucagon and insulin antibodies to calculate the ratio between these two cells area in the pancreas (A/B ratio). In order to measure the size of the beta-cell nucleus, an immunofluorescence staining of the nucleus and insulin was carried out. Data were gathered from type 2 diabetic subjects (n=19) and normal controls (n=8). RESULTS: Although there was no statistical difference, we observed the tendency of decrease of beta-cell mass and increase of alpha-cell mass in the pancreas of type 2 diabetic patients. The ratio of alpha-to beta-cell area in islet (A/B ratio) increased to 0.81+/-0.76 in diabetic patients compared to control with 0.26+/-0.25 (p<0.01). The mean of the A/B ratios of the islets more than 22,000 micro m2 was 1.64+/-1.10, whereas that of the islets less than 22,000 micro m2 was 0.73+/-0.67 in type 2 diabetic patients (p<0.01). The size of the beta-cell nucleus in both diabetic subjects and normal controls was bigger than that of exocrine cells (p<0.05) and 2.9% of beta-cells in type 2 diabetic subjects showed substantially enlarged nuclei more than M+5SD (M and SD means the average and standard deviation of nucleus size of exocrine cells, respectively) whereas this type of nucleus was found in only 0.5% of beta-cells in normal controls (p<0.05). CONCLUSION: The islet pathology in type 2 diabetes could be characterized by an expansion of alpha-cells associated with the selective loss of beta-cells. Some beta-cells found in diabetes showed a significant increase in size of the nucleus. Through the results from this study, we postulate that enlarged beta-cell nucleus and reverse of A/B ratio in the islets could be a marker of early senescence of beta-cells in patients with type 2 diabetes mellitus.

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