Background: Background: Background: Background: Cellular replacement therapy holds promise for the treatment of diabetes mellitus but donor tissue is severely limited.Human postnatal pancreatic ductal cells are a potential source of new beta cells.Therefore, we investigated the potential of human pancreatic ductal cells could be differentiated into endocrine cells that would be capable of secreting insulin in response to glucose.Methods: Methods: Methods: Methods: Cell fractions enriched with pancreatic ductal cells after human islet isolation were treated with streptozotocin to remove residual beta cells, grown in monolayer culture, changed the media for differentiation in the presence of activin A and glucose, supplemented with 10% FCS.The differentiation markers, insulin secretion and cell proliferation were examined.Result: Result: Result: Result: No insulin was detectable in cell preparations after 5 days of treatment with streptozotocin.In monolayer culture, 80% of the streptozotocin-treated pancreatic ductal cells expressed cytokeratin-19.Cell cultures with a high proportion of cytokeratin-19 cells had greater plasticity for differentiation into cells with phenotypic and functional markers of beta cells.This property were significantly enhanced by treatment of activin A and glucose.The differentiated human pancreatic ductal cells secreted insulin sensitively responded with high glucose. Conclusion: Conclusion: Conclusion:Conclusion: Human pancreatic ductal cells are a potential source of new glucose -induced insulin producing cells that may be developed further for clinical use.Therefore, the present data support a possible role for human adult pancreatic ductal cells, following expansion and differentiation, as a source of insulin by transplantation cells to type I diabetes patients.(
Background: The relative effect of diabetes on the risk of cardiovascular disease in Asian population is much the same as that in Western populations. Although multiple atherosclerotic risk factors have been documented in Asia, precise estimates of vascular reactivity might provide more critical informations for the prevention and the control of diabetes-related cardiovascular mortality and morbidity. The aims of this study were to estimate the vascular reactivity directly and evaluate its relationship with other cardiovascular risk factors and carotid intimal-media thickness (IMT) in newly-diagnosed Korean type 2 diabetic patients. Methods: We measured flow-mediated vasodilation (FMD) and endothelial-independent vasodilation (EID) of the brachial artery using high-resolution ultrasonography in total of 121 (M; N = 68, F; N = 53) diabetic patients. We assessed conventional cardiovascular risk factors such as age, smoking, obesity, hypertension, hyperlipidemia or family history of cardiovascular disease and analyzed the association among FMD/EID with cardiovascular risk factors, carotid IMT or the total number of risk factors. Results: The mean values of age, smoking, BMI, waist, systolic blood pressure and diastolic blood pressure were 51.2 ± 12.3 years, 11.0 ± 15.8 pack years, 25.0 ± 3.2 kg/m 2 , 86 ± 9 cm, 123 ± 16 mmHg and 79 ± 12 mmHg. The mean values of HbA1c, fasting blood glucose, total cholesterol, triglyceride, LDL-cholesterol and HDL-cholesterol were 8.4 ± 2.0%, 166 ± 51 mg/dL, 187 ± 37 mg/dL, 166 ± 143 mg/dL, 114 ± 30 mg/dL and 46 ± 12 mg/dL. FMD and EID were estimated by 6.1 ± 2.8% and 16.6 ± 5.6% respectively. The mean/maximal carotid IMT were 0.63 ± 0.12/0.76 ± 0.16 mm and the number of risk factors besides diabetes mellitus were 2.3 ± 1.3. After adjusting age, FMD was associated only with smoking, but EID was associated with smoking, systolic/diastolic blood pressure, mean/maximal carotid IMT and number of risk factors by partial correlations. Age, smoking and EID were independent risk variables for carotid IMT, analyzed by multiple regression test. Conclusion: These findings suggest that impaired vascular reactivity detected by EID is closely related to carotid IMT, an useful surrogate marker for atherosclerosis, in newly-diagnosed Korean type 2 diabetic patients. (J Kor Diabetes Assoc 31:498~506, 2007)
Background: Korean type 2 diabetic patients are known to differ from western diabetes because of their unique characteristics, such as non-obese but centrally obese anthropometry and relatively more insulin secretory defects than insulin resistance compared to western diabetic patients. Methods:We recruited 1,646 diabetic patients in the present study and excluded the 45 patients with fasting C-peptide < 0.20 nmol/L.We had assessed insulin secretion by fasting serum C-peptide level and insulin resistance by short insulin tolerance test (Kitt ; rate constant for plasma glucose disappearance, %/min) in the private diabetes clinic.The insulin secretory defect was divided by severe (C-peptide < 0.37 nmol/L), moderate (C-peptide 0.37~0.56nmol/L), and normal (C-peptide ≥ 0.57 nmol/L) group.The insulin resistance was divided by insulin resistant (IR) (Kitt < 2.5 %/min) and insulin sensitive (IS) (Kitt ≥ 2.5 %/min) group. Results:We analysed the data of 1,601 type 2 diabetic patients (831 men and 770 women, age 56.5 ± 10.8 years, duration of diabetes 9.6 ± 7.3 years).The prevalence of BMI ≥ 25.0 kg/m 2 is 42.5% and BMI ≥ 23.0 kg/m 2 is 70.2%.The prevalence of abdominal obesity (waist ≥ 90 cm in men and 80 cm in women) is 45.2%(36.0% and 55.2%, respectively in men and women).Fasting C-peptide level is 0.64 ± 0.29 nmol/L and Kitt value is 2.03 ± 0.96%/min.According to fasting C-peptide level, the degree of insulin secretory defect were severe (13.1%), moderate (33.0%) and normal (53.9%).According to Kitt value, the IR group is 70.6% and the IS group is 29.4%. Conclusion:Obese type 2 diabetes is markedly increasing in Korea.Therefore, the major problem in Korean type 2 diabetic patients is being changed into insulin resistance instead of insulin secretory defect.(J Kor Diabetes Assoc 31:123~129, 2007)
Background: Metabolic syndrome is associated with an increasing incidence of diabetes and cardiovascular disease.The relationship between the amount of alcohol consumption and the prevalence of metabolic syndrome is controversial.Our study was performed to evaluate the relationship between alcohol consumption and the prevalence of metabolic syndrome in Korean men.Also we examined the correlation of liver markers, including alanine transaminase (ALT) and γ-glutamyl transferase (GGT) with the development of metabolic syndrome. Methods:We enrolled 1,775 Korean men (mean age 40.0 ± 5.8 years) who were undergone health check-ups in our hospital.Each component of metabolic syndrome was measured by using the American Association of Clinical Endocrinologists (AACE) criteria.The subjects were divided into 4 subgroups according to the amount of alcohol consumption; Group 1: no consumption, 2 (mild): those consumed less than 200 g/week, 3 (moderate): those consumed 200~399 g/week, 4 (heavy): those consumed more than 400 g/week. Results:The prevalence of metabolic syndrome was 24.6%.There were significant positive correlations between the amount of alcohol consumption blood pressure, triglyceride, fasting blood glucose, GGT levels and HDL cholesterol levels.But the odds ratios for metabolic syndrome were not significantly increased in subjects with moderate alcohol consumption.The odds ratios for the metabolic syndrome significantly increased in proportion to the increasing levels of ALT and GGT. Conclusion:Although alcohol consumption didn't increase the prevalence of metabolic syndrome, the amount of alcohol consumption had significant positive correlation with components of metabolic syndrome in Korean men, and elevated ALT and GGT levels could strongly associate with the prevalence of metabolic syndrome.(
Background: Nuclear receptors are involved in the cell growth, development, differentiation, and metabolism.The orphan nuclear receptor SHP which lacks a DNA-binding domain is a negative regulator of nuclear receptor signaling pathways.In pancreas, SHP regulate transcriptional activity of HNF3 and HNF4 through binding them and BETA2 which is involved in beta cell differentiation and insulin production.Here, we examined transcriptional activity changes of genes expressed in beta cell when SHP was overexpressed. Method:INS-1 cells of passage number 24 -30 were prepared.Affimetrix DNA chip was used to examine gene expression in INS-1 cell when SHP was overexpressed.INS-1 cells were infected with adenovirus-SHP to overexpress SHP.To confirm the result of DNA chip, we used real time RT-PCR.Result: When SHP was overexpressed by adenovirus-SHP transfection, FXR, Transforming growth factor, beta 2, fructose-1,6-bisphosphatase 2, bone morphogenetic protein 4 genes expression were increased.Contrarily, Activating transcription factor 2, Glycogen synthase kinase 3 alpha, Nur 77, fibroblast growth factor 14 genes expression were decreased.We confirmed DNA microarray analysis by real time RT-PCR.FXR, tribbles homolog 3 (Drosophila), fructose-1,6-bisphosphatase 2, CD36 genes expression were increased in real time RT-PCR.Nur 77 and cAMP response element modulator genes expression were decreased in real time RT-PCR. Conclusion:we identified several genes which expression are regulated by SHP in pancreas beta cell.These results help to explain how SHP act in the various metabolism of pancreas beta cell.(J Kor Diabetes Assoc 31
Background: Once daily injection and 24 hour lasting glucose lowering effect of insulin glargine had recently changed a perception about the early insulin treatment of type 2 diabetic patients.This study was performed to investigate therapeutic efficacy of combined therapy with insulin glargine and glimepiride in Korean type 2 diabetic patients, who had received oral hypoglycemic agents (OHA) or conventional insulin therapy.Methods: Total of 192 patients who needed to change the previous therapy because of uncontrolled diabetes or hypoglycemia were included and followed for about 6 months.Two groups of prior treatment modality were analyzed; OHA group (n = 54, 28.1%), conventional insulin therapy group in combination with or without OHA group (n = 138, 71.9%).The primary end point was changes in HbA1c according to baseline characteristics such as prior treatment modality, HbA1C, c-peptide, duration of diabetes mellitus, body mass index and prior used conventional insulin doses.Secondary end point was the dose conversion ratio of insulin glargine to prior used insulin in patients who had one or two insulin therapy.We also evaluated the level of the patients' satisfaction on the glucose lowering effects and the convenience for use of device. Results:The differences of HbA1c according to prior treatment groups were -0.78 ± 1.76 % in OHA group and 0.07 ± 1.44 % in conventional insulin group with or without OHA group.The HbA1c improved better when baseline HbA1c was higher than 9%, c-peptide was higher than 0.6 ng/mL, duration of diabetes was shorter than 15 years, BMI was lower than 30 kg/m 2 and prior conventional insulin dose was less than 30 IU.However, those effects were attenuated in subjects having duration of diabetes longer than 16 years, BMI higher than 30 kg/m 2 and prior insulin dose more than 40 IU.Dose conversion ratio of the insulin glargine to prior insulin was 0.78 ± 0.30 and showed a tendency to increase in patients who have prior insulin dose more than 40 IU.The scores of the patients' subjective satisfaction on insulin glargine were all high, irrespective of the changes of HbA1c.Conclusions: Once daily injection of insulin glargine and oral ingestion of glimepiride can be recommended 접수일자: 2007년 7월 18일, 통과일자: 2007년 9월 14일, 책임저자: 민경완, 을지의과대학교 내과 *
Background: Previous studies have suggested that polymorphisms in and around the aldose reductase (AR) gene are associated with the development of diabetic microvascular disease.This study explored the hypothesis that the polymorphisms of the (A-C)n dinucleotide repeat sequence, located at 2.1 kilobase (kb) upstream of the transcription start site of AR gene, modulate the risk of diabetic neuropathy (DN).Methods: 66 patients with DN, 30 without microvascular complications (MC) after 20 years of diabetes, and 87 normal healthy controls were studied.To test highly polymorphic microsatellite marker 2.1 kb upstream of the initiation site of the AR gene, we performed polymerase chain reaction using the primer labeled with fluorescent dye and GeneScan by ABI prism 377 automated DNA sequencer and ABI Genotyper software 2.0.Results: Seven alleles (Z-6, Z-4, Z-2, Z, Z+2, Z+4 and Z+6) were identified.Z-2 allele was more frequently observed in patients with DN (77.3%) than in those without MC (43.3%, P = 0.007).The subgroup of patients who developed DN within 5 years after the diagnosis of diabetes also had higher frequency of Z-2 allele (91.7%) compared to those without MC (43.3%, P = 0.028).On the contrary, Z+6 allele tended to be more frequent in patients without MC (10.0%) than in those with DN (0%, P = 0.063). Conclusion:These results support the hypothesis that environmental-genetic interactions may modulate the risk of neuropathy in patients with diabetes.Particularly, the Z-2 allele, in the presence of diabetes, may be associated with the development of DN. (
BACKGROUNDLeptin is a hormone which is produced in adipose tissue and regulates food intake and body weight. Leptin is known to correlate with body adiposity such as body mass index. Blood leptin concentration is not different between non-diabetics and diabetics. And It affect not only food intake but may be one of the key factors in the developement of insulin resistance. Recent studies suggest a complex relationship between leptin and insulin resistance or insulin. Therefore we examined the relationship between leptin and anthropometric, biochemical parameters, and insulin resistance in type 2 diabetics. METHOD: The study subjects were 144 patients with type 2 diabetes who visited Kyungpook national university hospital. Anthropometric parameters such as body fat mass, soft lean mass, BMI, arm circumference, skin fold thickness of several sites were measured. Percent body fat were calculated from Brozek fomula, body density were calculated from Jackson and Pollock fomula. Fasting blood leptin and metabolic varables such as C-peptide, HbA1C, insulin, HDL, LDL, TG, total cholesterol, FFA, HOMA-IR were measured. The relationships of blood leptin concentration with clinical data were analyzed with SPSS program. RESULT: Blood leptin concentrations were 8.2 +/- 5.39 ng/mL in women with type 2 diabetes and 5.1 +/- 5.55 ng/mL in men with type 2 diabetes (P-value: 0.01). Percent body fat, FFA were higher in women than men but arm circumference, soft lean mass, waist circumference were higher in men than women (P-value < 0.05). Leptin concentration correlated with BMI, percent body fat, insulin, TG, body fat mass, waist circumference, HOMA-IR. And insulin, C-peptide, total cholesterol, TG were also correlated with leptin only in women with type 2 diabetes. Waist circumference and percent body fat were independent variables which influence blood leptin concentration in multiple regression analysis. CONCLUSION: Blood leptin concentrations are related to parameters such as percent body fat, waist circumference, BMI, body fat mass, insulin, TG, HOMA-IR in type 2 diabetics. The relationship between leptin and obesity or HOMA-IR suggests that leptin may be a one of factors in developement of insulin resistance.
Clusterin is a highly glycosylated heterodimeric glycoprotein that plays diverse biological roles in various organs.The secreted clusterin has been established as a major form of the protein that exerts diverse tissue effects.For instance, clusterin is known to act in cell protection through the actions of extra-cellular molecular chaperones.In the extracellular milieu, clusterin participates in specific interactions with a diverse array of native biological molecules including LRP-2 (Lipoprotein receptor-related protein 2, also known as gp330 or megalin), which is involved in ligand endocytosis at the surfaces of certain epithelia.Clusterin is expressed transiently in developing and differentiating endocrine pancreatic cells and might be involved in pancreas development.This transient expression of clusterin at specific time points of pancreas development and cell differentiation during pancreas regeneration implies that the protein is a regulatory factor for cytodifferentiation as well as for replication.A specific action of the clusterin in the reconstruction and remodeling of the endocrine pancreas has been demonstrated.It also strongly stimulates duct cell differentiation into insulin-secreting cells under in vitro culture conditions.Clusterin appears thus as a potent regulator of insulin cell morphogenesis.(
-Purpose: To make protocol on diabetic foot ulcer, with making use of this protocol, investigate hospitalized patients who have had diabetic foot wound and define pattern, characteristics and problems of diabetic foot in hospitalized patientsMaterials and Methods: From Oct. 2002 to Sep. 2003, Seventy-two patients who had been admitted to our hospital due to treatment of diabetic foot wound studied with use of the protocol designed by the authors.Results: The mean age of patients was 64.3 years and male patients were twice as many as female. The most common cause of hospitalization was infection of diabetic foot (77.7%). As a basic pathology of diabetic foot, the main pathology of diabetic foot was the neuropathy that is four times more than vasculopathy. The causations of wound were infection with no specific cause (40.0%). No statistical difference was found between timing of hospitalization and the results of treatment in vasculopathic group but in neuropathic ulcer group, the major procedure such as amputation, and the times of debridement in operation room and are more common in patients who were hospitalized after 3rd days of beginning of symptoms than within 3rd day. Conclusion: The education that the patient having a foot symptom have to visit the hospital as soon as possible on patients is important to prevent morbidity of diabetic foot wound, long hospitalization and amputation. The protocol that we are presenting can be modified for other study related to diabetic foot. (J Kor Diabetes Assoc 31:89~95, 2007)
BACKGROUNDDiabetic retinopathy is a leading cause of adult blindness. Some patients show early development and progression of diabetic retinopathy despite of apparently good glycemic control. This is suggesting the involvement of other contributing factors. Recent studies have shown that retinopathy and GAD autoantibody (GADA) show an inverse relationship immunologically. This study is designed to investigate the clinical manifestation of diabetes who are positive for GADA and the relationship between GADA and diabetic retinopathy. METHODS: Type 1 diabetic patients & LADA patients who had visited Yeungnam university Medical Center from 1988 to 2005 were involved. We reviewed the pathologic and laboratory records of these patients and investigated the development of diabetic microvascular complications. RESULTS: Compared with patients who had GADA negative diabetes, patients with GADA positive diabetes had lower prevalence of diabetic retinopathy (GADA negative subject: 25.8% vs. GADA positive subject: 9.6%, P < 0.05). CONCLUSION: We confirmed that diabetic retinopathy and GADA showed an inverse relationship. It seems quite probable that GADA may contribute to the prevention of retinopathy. Further research should be needed concerning the effect of GADA on diabetic retinopathy.
Background: Transforming growth factor-β is known to play a role in the interaction between metabolic and hemodynamic factors in mediating accumulation of extracellular matrix in the diabetic nephropathy.TGF-β1 gene polymorphism was associated with circulating TGF-β levels and influenced the pathogenesis of fibrotic diseases including diabetic nephropathy.In this study, we examined the relationship between TGF-β1 gene codon 10 polymorphism and type 2 diabetic nephropathy with more than 10-year history of disease. Methods:We conducted a case-control study, which enrolled 325 type 2 diabetes.A total of 176 patients with diabetic nephropathy were compared with 149 patients without diabetic nephropathy.TGF-β1 codon 10 genotyping was determined using polymerase chain reaction with sequence specific primers method.Results: Distribution of TGF-β1 codon 10 genotype in the patients either with nephropathy or without nephropathy is confined to Hardy-Weinberg equilibrium.The patients with nephropathy have higher frequency of TGF-β1 GA/GG genotypes than the patients without nephropathy [GA/GG:AA = 119 (67.6%) : 57 (32.4%) vs. 80 (53.7%) : 69 (46.3%),P < 0.05].Among patients with diabetic nephropathy, those with TGF-β1 GA/GG genotypes had higher serum levels of total cholesterol and LDL-cholesterol. Conclusion:Our results suggest that TGF-β1 gene codon 10 polymorphism may contribute to the type 2 diabetic nephropathy.(
당뇨병 제 31 권 제 5 호, 2007 증 례 444 서 론 제1형 당뇨병은 췌장 내 베타세포가 파괴되어 인슐린결 핍을 유발하고, 생존을 위하여 인슐린이 필요한 상태를 말 한다.세계보건기구와 미국당뇨병학회는 제1형 당뇨병을 자 가면역성 제1형 당뇨병(autoimmune diabetes mellitus; type 1A)과 특발성 제1형 당뇨병(idiopathic diabetes mellitus; type 1B)으로 세분하였다 1) .자가면역성 제1형 당뇨병은 자가면역반응으로 베타세포가 선택적으로 파괴되어 발생하며 주로 소아 및 청소년기에 진 단되지만 성인기에 진단되기도 한다
Autoantibody negative fulminant type 1 diabetes mellitus is a novel subtype of type 1 diabetes, which is characterized by a remarkably abrupt onset, metabolic derangement such as diabetic ketoacidosis at diagnosis, low HbA1c level at onset and a negative islet-related autoantibodies. The prevalence of fulminant type 1 diabetes has large difference between Japan and other countries. The precise reason for this regional variation remains to be clarified. One of the possible explanations is genetic background such as genotype of class II HLA molecule. In addition, environment factors including viral infection are suggested as possible pathogenesis of the disease. Only a few cases with fulminant type 1 diabetes have been reported outside Japan, and most of these cases with definite diagnosis have been reported in Korea. We report here on two Korean patients that met the criteria for diagnosis of fulminant type 1 diabetes in accordance with their HLA genotypes. (J Kor Diabetes Assoc 31:372~376, 2007)
Ketosis-prone type 2 diabetes (KPD) has been characterized as diabetes with severe insulin deficiency at diagnosis associated with ketosis or ketoacidosis without a precipitating cause. Improvement in beta-cell function and insulin sensitivity by aggressive diabetic management could allow discontinuation of insulin therapy within a few month of therapy. These subjects are usually obese, have a strong family history of diabetes, absence of β-cell autoimmune markers and lack of human leukocyte antigen genetic association. This clinical presentation has been reported primarily in African and African Americans, but rare in Asian and white person. We recently experienced a case of KPD in Korea and present it with literature review. (J Kor Diabetes Assoc 31:293~296, 2007)
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.
Mitochondrial dysfunction contributes to a large variety of human disorders, ranging from neurodegenerative and neuromuscular diseases, obesity, and diabetes to ischemia-reperfusion injury and cancer. Increasing pharmacological efforts toward therapeutic interventions have been made leading to the emergence of 'Mitochondrial Medicine' as a new field of biomedical research. The identification of molecular mitochondrial drugs targets in combination with the development of methods for selectively delivering biologically active molecules to the site of mitochondria will eventually launch a multitude of new therapies for the treatment of mitochondria-related diseases, which are based either on the selective protection, repair, or eradication of cells. Yet, while tremendous efforts are being undertaken to id entify new mitochondrial drugs and drug targets, the development of mitochondria-specific drug carrier systems is lagging behind. To ensure a high efficiency of current and future mitochondrial therapeutics, delivery systems need to be developed, which are able to selectively transport biologically active molecules to and into mitochondria within living cells. (J Kor Diabetes Assoc 31:187~192, 2007)
