- The Association of Aldose Reductase Gene Polymorphisms with Neuropathy in Patients with Type 2 Diabetes.
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In Kyong Jeong, Kyong Soo Park, Min Kyong Moon, Jae Hyeon Kim, Chan Soo Shin, Seong Yeon Kim, Hong Kyu Lee
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Korean Diabetes J. 2007;31(3):274-283. Published online May 1, 2007
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DOI: https://doi.org/10.4093/jkda.2007.31.3.274
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Abstract
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- 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.
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- The Association between Serum GGT Concentration and Diabetic Peripheral Polyneuropathy in Type 2 Diabetic Patients
Ho Chan Cho Korean Diabetes Journal.2010; 34(2): 111. CrossRef
- Association between Genetic Polymorphisms in Hepatocyte Nuclear Factor 4alpha and Type 2 Diabetes in Koreans.
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Eun Jung Lee, Soo Heon Kwak, Sun Wook Jo, Hyung Jin Choi, Hyoung Doo Shin, Min Kyong Moon, Young Min Cho, Hak Chul Jang, Kyong Soo Park, Houng Kyu Lee
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Korean Diabetes J. 2006;30(1):10-16. Published online January 1, 2006
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DOI: https://doi.org/10.4093/jkda.2006.30.1.10
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Hepatocyte nuclear factor-4alpha (HNF-4alpha) is a member of transcription factor network which is essential for the development and function of the beta cell. Furthermore mutations in the HNF-4alpha gene have been known to cause maturity-onset diabetes of the young. Therefore we aimed to examine the association between polymorphisms in the HNF-4alpha gene and the risk of type 2 diabetes (T2DM) and its related phenotypes in the Korean population. METHODS: Two single nucleotide polymorphisms (SNPs) in the HNF-4alpha gene, g.4681C>T and HNF-4alpha g.12352C>T (Thr139Ile), were genotyped in unrelated T2DM (n=760) and non-diabetic subjects (n=303). The genetic associations between these SNPs and the risk of T2DM and metabolic phenotypes were analyzed. RESULTS: There was no significant association between genetic polymorphisms in the HNF-4alpha and the risk of T2DM. However HNF-4alpha g.4681C>T increased total cholesterol in the recessive model (P = 0.02) and showed marginal association with fasting plasma glucose (P = 0.049) in the additive model. CONCLUSION: There was no significant association between genetic polymorphisms and the risk of T2DM in the Korean populations. But HNF-4alpha g.4681C>T was associated with higher level of total cholesterol and fasting plasma glucose.
- Glutathion S-Transferase M1 Gene Polymorphism is Associated with Type 2 Diabetic Nephropathy.
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Jae Hyeon Kim, Min Kyong Moon, Sang Wan Kim, Hyoung Doo Shin, Young Hwan Hwang, Curie Ahn, Hak Cheol Jang, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee
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Korean Diabetes J. 2005;29(4):315-321. Published online July 1, 2005
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Oxidative stress may be a determinant of the development of diabetic nephropathy. Glutathione S-transferases(GST) can work as an endogenous antioxidant to protect cells from oxidative stress. Homozygous deletion of the mu and theta subclasses of GST(GST-M1 and GST-T1), and Val105Ile polymorphism of the pi subclass of GST(GST-P1) are associated with antioxidant enzyme activity. In this study, whether the Val105Ile of GST-P1, null genotype of GST-M1 and GST-T1 are associated with type 2 diabetic nephropathy were examined. METHODS: These GST subclasses were genotyped in 361 type 2 diabetic patients with retinopathy; the subjects were divided into two groups, those with an end stage renal disease(ESRD)(the case group n=177) and those(the control group, n=184) showing no signs of renal involvement. RESULTS: The frequencies of the GST-P1 Ile105Val and GST-T1 null genotypes were no different between the cases and controls. However, the frequency of the GST-M1 null genotype was significantly higher in the cases than the controls(61.7% vs. 51.1%, chi-square=4.09, P=0.043), which was still significant after correction for age, sex and duration of diabetes (P= 0.044). In addition, the GST-M1 null genotype showed an increased frequency between the controls and the cases with long and short durations of type 2 diabetes until the onset of ESRD(51.1, 58.9 and 65.5%, respectively; chi-square for trend=5.12, P=0.024). CONCLUSION: This is the first study to suggest that the GST-M1 gene polymorphism might contribute to the development of ESRD in type 2 diabetic patients.
- Genetic Association of Adiponectin Polymorphisms with Risk of Type 2 Diabetes Mellitus.
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Yun Yong Lee, Nam Seok Lee, Young Min Cho, Min Kyong Moon, Hye Seung Jung, Young Joo Park, Hong Je Park, Byoung Soo Youn, Hong Kyu Lee, Kyong Soo Park, Hyoung Doo Shin
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Korean Diabetes J. 2003;27(6):438-448. Published online December 1, 2003
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Adiponectin, an adipocyte-secreted protein, is known to modulate insulin sensitivity, glucose homeostasis and the development of atherosclerosis. Recently, several single nucleotide polymorphisms (SNPs) in the adiponectin gene have been reported to be associated with type 2 diabetes and components of the insulin resistance syndrome. METHODS: The frequencies of SNP T45G and G276T of the adiponectin gene was examined in 493 unrelated type 2 diabetic and 136 non-diabetic control Korean subjects. The clinical characteristics and plasma adiponectin levels of the subjects were compared within these genotypes. RESULTS: The T allele at SNP45 was significantly more frequent in the type 2 diabetes than in the control subjects (71.6 vs. 64.3%, p=0.013). The subjects with the G/G genotype of SNP45 were at reduced risk for type 2 diabetes (OR: 0.495, 95% CI 0.246-0.995, p=0.048) compared with those having the T/T genotype. However, there were no statistically significant differences in allele the frequencies (G frequency in the control vs. the diabetic group 73.9 vs. 68.9%, p=0.106) and genotype frequencies at SNP276 between groups. The subjects with the T/T genotype at SNP45 had higher a body mass index (24.6+/- 3.1 vs. 24.1+/-2.8 kg/m2, p=0.036) and serum triglyceride levels (2.03+/-1.31 vs. 1.87+/-1.38 mmol/1, p=0.041) than the T/G+G/G genotypes in the diabetic group. Those with the T/T genotype also had lower plasma adiponectin levels than those without T/T genotype at SNP45 in the control group (6.11+/-3.10 vs. 8.24+/-4.24 g/mL, p=0.043). There was a similar trend in diabetic group, but this did not reach statistical significance (4.32+/-2.81 vs. 4.96+/-3.26 g/mL, p=0.097). The SNP276 had no association with the clinical features of insulin resistance or plasma adiponectin level. CONCLUSION: The T/T genotype of SNP45 in the adiponectin gene was associated with a low adiponectin level, high body mass index, the serum triglyceride level and risk of type 2 diabetes mellitus. The SNP276 in the adiponectin gene may not be an important determinant of insulin resistance or type 2 diabetes in Korean subjects.
- Clinical Characteristics of Post-transplantation Diabetes Mellitus associated with Tacrolimus Therapy after Kidney Transplantation.
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Young Min Cho, Hye Seung Jung, Yun Yong Lee, Min Kyong Moon, Suk Kyung Kim, Hyun Jung Jeon, Curie Ahn, Jong Won Ha, Sang Joon Kim, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee
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Korean Diabetes J. 2002;26(6):509-519. Published online December 1, 2002
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Post-transplantion diabetes mellitus (PTDM) is a major metabolic complication of transplantation and shows a variable incidence among studies with different population or different definition. We examined the incidence and the risk factors of PTDM in the Korean patients with tacrolimus-based immunosuppression following kidney transplantation, and also investigated the change of insulin secretory capacity. METHODS: Twenty-one patients using tacrolimus as primary immunosuppressant were recruited and tested with serial 75-g oral glucose tolerance test (OGTT) at 0, 1, 3, and 6 months after kidney transplantation. RESULTS: According to the American Diabetes Association criteria, the incidence of PTDM was 57.1% (12 of 21). Baseline characteristics of PTDM group were old age (especially > 40 yr), high body mass index, high fasting glucose, high plasma insulin, and increased insulin resistance. The insulin secretory capacity in PTDM group was maximally suppressed 3 months after transplantation and was gradually restored thereafter along with dose reduction of tacrolimus. CONCLUSIONS: Attention should be paid to the patients, especially who are over 40 yr of age, throughout the high dose tacrolimus therapy.
- Association between Type 2 Diabetes and Genetic Variations in Uncoupling Protein 2, beta3-Adrenergic Receptor, and Peroxisome Proliferator-Activated Receptor gamma in Korean.
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Min Kyong Moon, Young Min Cho, Hye Seung Jung, Tae Yong Kim, Yun Yong Lee, Joong Yeol Park, Ki Up Lee, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, Hyoung Doo Shin
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Korean Diabetes J. 2002;26(6):469-480. Published online December 1, 2002
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Type 2 diabetes mellitus is a multifactorial disease influenced by numerous genetic and environmental factors. The uncoupling proteins, 2 (UCP2), beta3-adrenergic receptor ADRB3, and peroxisome proliferator-activated receptor gamma PPAR gamma, are genes involved in energy expenditure and fatty acid metabolisms, ans are therefore regarded as candidate genes for type 2 diabetes. In this study, we examined whether the known polymorphisms of UCP2, ADRB3 and PPAR gamma are associated with type 2 diabetes in the Korean population. METHODS: We studied 516 type 2 diabetic patients and 147 control subjects. The enrollment criteria for the control subjects were as follows; age > 60 years, no family history of diabetes in their first-degree relatives, a fasting plasma glucose (FPG) < 6.1 mmol/L, and a HbA1C < 5.8%. Height, weight, waist and hip circumference, FPG, 2 hour-plasma glucose after 75g-glucose load (2h-PG), blood pressure, lipid profile, and fasting insulin level were measured. The Ala55Val polymorphism of the UCP2, Trp64Arg polymorphism of the ADRB3, and Pro12Ala polymorphism of the PPAR gamma were determined by single base extension method. RESULTS: The allele frequency of the Ala55Val variant of the UCP2 tended to be higher in the control subjects than in the type 2 diabetic patients (0.497 vs. 0.456, p=0.064). The allele frequencies of the Trp64Arg polymorphism of the ADRB3, and the Pro12Ala polymorphism of the PPAR gamma, were comparable between the diabetic patients and the control subjects (0.141 vs. 0.152 and 0.033 vs. 0.041, respectively). In the control subjects, the Ala55Val polymorphism of the UCP2 was associated with a significantly lower 2h-PG compared to the wild type (6.0 +/- 0.8 mmol/L vs. 6.6 +/- 0.7 mmol/L, p=0.002). The female control subjects, with the ADRB3 Trp64Arg variant, had a significantly lower triglyceride level than those without the variant (1.36 +/- 0.53 mmol/L vs. 1.74 +/- 0.82 mmol/L, p=0.020). The type 2 diabetic patients, with the ADRB3 Trp64Arg variant showed a significantly lower body mass index (23.6 +/- 2.6 kg/m2vs. 24.6 +/- 3.0 kg/m2, p=0.001). The PPAR gamma Pro12Ala variant, was not associated with any of the features of insulin resistance. The combined genotype of the Val allele of UCP2, Trp allele of ADRB3 and Ala allele of PPAR gamma was less frequent among the type 2 diabetes patients than the control subjects (0.020 vs. 0.056, p=0.039). CONCLUSION: The Ala55Val variant of the UCP2, the Trp64Arg variant of the ADRB3 and the Pro12Ala variant of the PPAR gamma, were not associated with type 2 diabetes in the Korean population. However, the Ala55Val variant of the UCP2 was associated with a lower 2h-PG in the control subjects and the Trp64Arg variant of the ADRB3 was associated with a lower triglyceride level in the female control subjects. Further study may be required to elucidate if the combined genotype of Val allele of UCP2, Trp allele of ADRB3 and Ala allele of PPAR gamma would be protective against type 2 diabetes.
- Clinical Characteristics of S20G Mutation of Amylin Gene in Korean Type 2 Diabetic Patients.
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Young Min Cho, Min Kim, Yun Yong Lee, Min Kyong Moon, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee
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Korean Diabetes J. 2002;26(5):377-382. Published online October 1, 2002
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Islet amyloid deposition, which is mainly composed of amylin, is a characteristic pathological finding in patients with type 2 diabetes mellitus. A missense mutation of amylin at amino acid 20, from Serine to Glycine (S20G), has been shown to be associated with type 2 diabetes in Japanese. In this study, we examined the frequency and clinical characteristics of the S20G mutation in Korean type 2 diabetic patients. METHODS: We studied 364 unrelated patients with type 2 diabetes from Seoul National University Hospital and compared them with 70 non-diabetic subjects. We measured their weight, height, blood pressure and the circumferences of their waist and hips, in order to obtain their prediabetic maximal body weight. Their Fasting plasma glucose, HbA1c, total cholesterol, triglyceride and high-density-lipoprotein (HDL) cholesterol were measured. To detect the S20G mutation, we used the polymerase chain reaction-restriction fragment length polymorphism method. The clinical features of the patients with the S20G mutation were compared with those without the mutation. RESULTS: The S20G mutation was found in 7 of the 364 diabetic patients (1.9 %) and in 1 of the 70 non-diabetic control subjects (1.4 %). The body mass index (BMI) of the patients with the S20G mutation was lower than in those with wild type (21.2+/-1.8 vs. 24.3+/-3.0 kg/m2; p<0.01). The prediabetic maximal BMI was also lower in the patients with S20G mutation (22.4+/-2.3 vs. 26.4+/-3.2 kg/m2; p<0.01) than in those with the wild type. The patients with the S20G mutation had a higher HbA1c level compared to those with the wild type (9.3+/-1.4 vs. 7.7+/-1.3%; p<0.01). CONCLUSION: The frequency of the S20G mutation of the amylin gene was 1.9% in the unrelated type 2 diabetic Korean patients. The S20G mutation is associated with a lower BMI and poor glycemic control.
- Correlation between Basal Insulin Requirements and Daily Administered Insulin Dosage in Diabetes.
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Min Kyong Moon, Jong Ho Ahn, Tae Yong Kim, Won Shik Shinn, Soo Lim, Young Min Cho, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee
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Korean Diabetes J. 2000;24(5):552-559. Published online January 1, 2001
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In patients who need insulin therapy, it is difficult to assess insulin requirements because of individual variability in insulin sensitivity and secretion. The aim of this study is to know that it is possible to achieve rapidly and efficiently normoglycemia based on insulin infusion algorithm and whether there is correlation between basal insulin requirements and daily administered total insulin dose. METHODS: Total 34 patients were enrolled. Insulin infusion was begun at 2:00 p.m., and bedside blood glucose concentration was measured at hourly intervals. The rate of insulin infusion was adjusted according to blood glucose levels. We compared insulin requirements to maintain normoglycemia (basal insulin requirements) with daily administered total insulin dose. RESULTS: At start, the mean blood glucose concentration was 14.9+/-4.7 mmol/L; by the first hour, it was 10.7+/-3.6 mmol/L; by the second hour, it was 7.4+/-3.1 mmol/L; when the infusion was discontinued, it was 5.7+/-1.0 mmol/L. This algorithm successfully inducted normoglycemia in all patients within 3.5+/-1.8 h. There was significant correlation between basal insulin requirements and daily administered total insulin dosage. And, daily administered insulin dose had significant correlation with first hour glucose concentration, first hour insulin infusion rate, second hour glucose concentration, second hour insulin infusion rate, and glucose concentration at the end. CONCLUSIONS: We concluded that normoglycemia can be achieved rapidly and efficiently based on insulin infusion algorithm. The present study suggested that we could predict daily insulin requirements through basal insulin requirements that we measured.
- Comparison of Clinical Characteristics of Impaired Fasting Glucose with Impaired Glucose Tolerance in Yonchon County.
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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
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Korean Diabetes J. 2000;24(1):71-77. Published online January 1, 2001
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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.
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