Diabetes & Metabolism Journal

Volume 26(6); December 2002

Review

AMPK and Type 2 Diabetes Mellitus.: Hyun Shik Son; Korean Diabetes J. 2002;26(6):443-450. Published online December 1, 2002

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Original Articles

Effect of Mouse Type and Human Type of CpG Oligonucleotide Vaccination on Development of Diabetes in NOD Mice.: Byong Jun Lee, Soo Kie Kim, Eon Sub Park, Hyun Jin Jang, Hyun Chul Cho, Myung Sook Shim, Mi Jin Kim, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 2002;26(6):451-459. Published online December 1, 2002

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Abstract PDF: BACKGROUND
Type 1 diabetes is autoimmune disease and the modulation of immune system could offer breakthrough to the disease. Unmethylated CpG motifs and their oligoneucleotide are potent immunostimulators that can rebalance autoimmune mechanism. To explore DNA based immunotherapy in type 1 diabetes, we vaccinated different types (mouse and human) of CpG ODN to NOD mice. METHODS: Forty 5 week-old female NOD mice were injected with 100 L (10 g) of mouse type CpG ODN or human type CpG ODN or 0.9% normal saline on inguinal area subcutaneously. Seven, 14, and 28 days later we injected to mice same dose of mouse type CpG ODN or human type CpG ODN or normal saline. Blood glucose was measured and mice were sacrificed when they were diabetic. Pancreata and serum were earned from sacrificed NOD mice to evaluate insulitis and insulin immunoassay. RESULTS: Though the final cumulative incidences of diabetes were not significantly different among groups, the tendency of delaying and suppressing the development of diabetes was observed in the early period of vaccination group of CpG ODN. Especially, mouse type CpG ODN was more effective for rodent species than human type CpG ODN. CONCLUSION: This result suggests that immunomodulation therapy using species- specific CpG motif may have a potential to control autoimmune process as well as dissecting T cell milieu in NOD mice.

Anti-obesity Effects of alpha-lipoic Acid in OLETF Rats.: Kee Ho Song, Ji Young Youn, Chul Nam Koong, Min Jeong Shin, Jae Won Ryu, Hye Sun Park, Min Seon Kim, Joong Youl Park, Ki Up Lee; Korean Diabetes J. 2002;26(6):460-468. Published online December 1, 2002

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Abstract PDF: BACKGROUND
Obesity is closely related to the development of type 2 diabetes mellitus, hypertension and cardiovascular disease. While the prevalence of obesity is rapidly increasing in most parts of the world, its effective treatment is not available due to the limited efficacy, and the side effects, of anti-obesity drugs. We unexpectedly found that administration of alpha-lipoic acid (ALA) resulted in a significant reduction in the body weight of rodents. This study aimed to investigate the mechanisms of the anti-obesity effect of ALA in the obese diabetic models of Otsuka Long Evans Tokushima (OLETF) rats. MATERIALS AND METHODS: Ten weeks old male OLETF rats were randomly assigned into one of three groups (n=6 per group): 1) the control group, fed with normal rat chow 2) the ALA group, fed with rat chow containing ALA (0.5% of food weight) and 3) the pair-fed group, fed with normal rat chow, but given the same amount of food as consumed by the ALA group. The body weight and food intakes were monitored for 3 weeks. At the end of the study, abdominal CT scans were performed to measure the visceral fat content. The energy expenditure and respiratory quotient were measured on days 3, 9 and 21 using an indirect calorimeter. The expression of the uncoupling protein-1 mRNA in the white and brown adipose tissues were determined by Northern blot analyses. The oxidation of fatty acids in the skeletal muscle, liver and adipose tissue was also measured. RESULTS: The administration of ALA induced a significant weight loss and reduction in food intake throughout the study period. The weight loss in the ALA group was greater than in the pair-fed group (p<0.05), suggesting an enhanced energy metabolism in the ALA group. In the ALA treated animals, the energy expenditure was significantly increased together with an elevated expression of UCP-1 mRNA in the brown, and an ectopic expression of UCP-1 mRNA in the white adipose tissues. The oxidation of fat in the brown adipose tissue and skeletal muscle was also increased after the ALA treatment, which was in line with the reduced respiratory quotient in the ALA group. The abdominal CT scan revealed a reduction in the visceral fat content in the ALA group compared to the control group. CONCLUSION: The present study demonstrated, for the first time, a novel anti-obesity action of ALA in obese OLETF rats, which proceeds through at least three different mechanisms: 1) reduction in food intake, 2) increase in energy expenditure and 3) enhancement of fat oxidation.

Association between Type 2 Diabetes and Genetic Variations in Uncoupling Protein 2, beta3-Adrenergic Receptor, and Peroxisome Proliferator-Activated Receptor gamma in Korean.: 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; Korean Diabetes J. 2002;26(6):469-480. Published online December 1, 2002

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Abstract PDF: BACKGROUND
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.

Differences in Dynamic Plantar Pressure in Type 2 Diabetics with or without Peripheral Neuropathy.: Gui Hwa Jeong, Ju Young Lee, Shin Won Lee, Chang Hoon Choi, Soon Hee Lee, Jung Guk Kim, Sung Woo Ha, Bo Wan Kim; Korean Diabetes J. 2002;26(6):481-489. Published online December 1, 2002

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Abstract PDF: BACKGROUND
Foot ulcers, and lower-extremity amputations, are relatively common complications of diabetes mellitus and their clinical management is very important. High plantar pressure is known to be a major risk factor of foot ulceration in diabetic patients. The EMED-system is used for the assessment of pressure distribution for the identification of focal areas at high risk of ulceration that merit protection from preventive footwear. However, a potential relationship between diabetic neuropathy and the plantar pressure has not been fully evaluated. Changes in the plantar pressure were measured in diabetic patients, both with and without peripheral polyneuropathy, using the EMED - AT system to clarify if diabetic neuropathy increases the plantar pressure. METHODS: Ninety seven patients with type 2 diabetes were divided into two groups on the basis of their peripheral polyneuropathy. No patient had a past history of foot ulceration. The clinical characteristics of 2 groups were analyzed, and their plantar pressures was measured using the EMED - AT system. These results were analyzed, with the EMED software program, after their division into ten masks for a so-called "regional analysis". The pressure time (PTI) and force- time (FTI) integrals were analyzed for each mask on both feet. RESULTS: The diabetic neuropathy (DN) group showed significantly higher FTI levels in both masks 05 (area of the 1st metatarsal head) and masks 08 (area of the hallux) than the diabetic control (DC) group. The PTI was also higher in right the mask 08 of the DN group than in the DC group. CONCLUSION: These results suggest that peripheral neuropathy to be an important risk factor, and predictor of diabetic foot ulcers, due to the increasing plantar pressure in some areas of the foot. Measurement of the plantar pressure may be a useful method for the diagnosis and monitoring of foot disorders in diabetic patients with peripheral neuropathy.

Relationship between C-peptide, Metabolic Control and Chronic Complications in Type 2 Diabetes.: Jeung Mook Kang, Won Young Lee, Ji Youn Kim, Jung Won Yun, Sun Woo Kim; Korean Diabetes J. 2002;26(6):490-499. Published online December 1, 2002

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Abstract PDF: BACKGROUND
Type 2 diabetes mellitus is a heterogeneous disease characterized by variable degrees of insulin resistance, impaired insulin secretion and increased glucose production. As the decline of beta-cell function in type 2 diabetes is very slow, the relationship between the insulin secretory capacity, the degree of metabolic control and chronic complications is still unclear. The determination of plasma C-peptide allows for the assessment of the endogenous insulin production, even in the presence of exogenous insulin administration. The aim of this study was to evaluate the relationship between the serum C-peptide level and metabolic parameters, and the complications in type 2 diabetes. METHOD: The clinical characteristics and laboratory findings, such as lipid profile, fasting plasma glucose, HbA1C and uric acid, were evaluated, and their relationships with chronic complications analyzed. We measured the serum C-peptide level by radioimmunoassay (RIA) in 384 type 2 diabetes mellitus patients. The patients were divided into quartile groups according to their fasting C-peptide levels (quartile 1: <1.73 ng/mL, n=95; quartile 2:>or=1.73 ng/mL and <2.38 ng/mL, n=95; quartile 3:>or=2.38 ng/mL and <3.18 ng/mL, n=98; quartile 4:>or=3.18 ng/mL, n=96). RESULTS: Patients in the lowest C-peptide quartile showed significantly higher durations of diabetes, HbA1C and postprandial plasma glucose values, and HDL-cholesterol. Conversely, the BMI, systolic blood pressure, total cholesterol and triglyceride were significantly higher in the highest C-peptide quartile. The prevalence of diabetic retinopathy and urinary protein excretion were higher in lowest quartile, and the diastolic blood pressure was highest in the upper quartile, but these were not statistically significant. The associations between C-peptide, and the duration of diabetes, BMI, total cholesterol, triglyceride, HDL cholesterol, postprandial 2 plasma glucose and systolic blood pressure remained significant, even after multiple adjustments. CONCLUSION: In type 2 diabetes, higher C-peptide levels are associated with a component of metabolic syndrome and lower C-peptide levels due to decreased cell reserves, associated with hyperglycemia and microvascular complications

Left Ventricular Mass Index Increases in Proportion to the Urinary Microalbumin Excretion Rate in Type 2 Diabetes.: Seung Ha Park, Won Young Lee, Sun Woo Kim; Korean Diabetes J. 2002;26(6):500-508. Published online December 1, 2002

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Abstract PDF: BACKGROUND
In type 2 diabetes, microalbuminuria is an early marker of the atherosclerotic process and of endothelial dysfunction. It has also been shown to be related with the prevalence and morbidity of renal and cardiovascular diseases, and is associated with other risk factors of vascular damage. Left ventricular hypertrophy (LVH) has long been established as a major independent marker of future cardiovascular morbidity and mortality, depending on the body mass and blood pressure load. In order to clarify any association between the urinary microalbumin excretion rate (UAER) and the left ventricular mass index (LVMI), which may explain the observed poor prognosis in these patients, we analysed the clinical characteristics and laboratory findings data of type 2 diabetes. METHODS: We conducted a cross-sectional study of 48 patients with type 2 diabetes, who had been echocardiographically assessed and their 24-h urine collection analyzed for UAER, and the patients with clinical evidence of heart and renal diseases were excluded. The patients were divided into two groups according to their mean LVMI value (Low LVMI group: LVMI <97 g/m2, n=26; High LVMI group: LVMI >or=97 g/m2, n=22). RESULTS: The UAER, and systolic and diastolic blood pressures, were higher in the High LVMI group, but age, sex, body mass index (BMI) and duration of diabetes were similar in both group. The correlation of UAER and systolic blood pressure with LVMI remained significant, even after a multiple regression analysis (p=0.042, p=0.01 respectively). CONCLUSION: The significant relationship between the UAER and LVMI was independent of blood pressure, age, sex, BMI, duration of diabetes and other cardiovascular risk factors in type 2 diabetes. Therefore, an increased UAER may play an important role in the development of LVH.

Clinical Characteristics of Post-transplantation Diabetes Mellitus associated with Tacrolimus Therapy after Kidney Transplantation.: 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; Korean Diabetes J. 2002;26(6):509-519. Published online December 1, 2002

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Abstract PDF: BACKGROUND
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.

Endogenous Streptococcus pneumoniae Endophthalmitis in Diabetic Patients.: Jung Min Lee, Hyun Shik Son, Ki Ho Song, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2002;26(6):520-524. Published online December 1, 2002

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Abstract PDF: Endogenous bacterial endophthalmitis is a rare disease, but has recently been been on the increase due to the increase of chronicity of disease, especially in immunocompromised hosts, and drug abusers, etc. In spite the aggressive topical and systemic management, endophthalmitis has poor prognosis. Therefore, early its diagnosis and appropriate treatment, mandatory for the improvement of the prognosis. We present a case of endogenous Streptococcus pneumoniae endophthalmitis, associated with bacteremia, but with no symptoms, with the exception of ocular pain, in a poorly controlled diabetic patient.

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