Diabetes & Metabolism Journal

Volume 22(1); March 1998

Original Articles

Progressive Decline of beta-cell Function in Type 2 Diabetes Mellitus.: Dong Seop Choi; Korean Diabetes J. 1998;22(1):1-10. Published online January 1, 2001

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Abstract PDF: No abstract available.

Current Trends in Pancreatic Islet cell Transplantation and Beta cell Regeneration.: Kun Ho Yoon; Korean Diabetes J. 1998;22(1):11-18. Published online January 1, 2001

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Abstract PDF: No abstract available.

Diabetic Angiopathy and Vascular Adhesion Molecule.: Doo Man Kim; Korean Diabetes J. 1998;22(1):19-22. Published online January 1, 2001

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Abstract PDF: No abstract available.

Elevated Levels of Soluble E-selectin and P-selectin in Patients with NIDDM.: Seok Dong Yoo, In Joo Kim, Yong Ki Kim; Korean Diabetes J. 1998;22(1):23-34. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although there is wide spread agreement that patients with NIDDM are at increased risk of the premature development of atherosclerosis, it is not totally clear why this is so. This may be related to the interaction of blood leukocytes with vascular endothelium resulting from a loss of normal metabolic control. The adherence of leukocytes to the endothelium is at least partly mcdiated by cell adhesion molecules. In this study, we evaluated the level of soluble E-selectin and P-selectin in blood of normal controls and patients with NIDDM, and studied its relation to glycemic control and identifiable factors influencing the level of soluble E-selectin and P-selectin. METHODS: Serum soluble E-selectin and plasma soluble P-selectin levels were measured by ELISA method in 24 NIDDM patients without macrovascullar disease and 14 normal controls matched with age, sex and body mass index. Clinical characteristics and laboratory findings such as fasting plasma glucose, HbA1c and lipid profile were evaluated, and their relation with the levels of E-selectin and P-selectin was analized. RESULTS: 1) The levels of E-selectin and P-selectin in NIDDM patients were significantly higher than those of normal controls(55.69+21.97 vs. 42.11+13.57ng/ mL, P<0.05 for E-selectin, 41.60+20.90 vs. 27.16 +7.12ng/mL, P 0.01 for P-selectin). 2) The levels of E-selectin and P-selectin were positively correlated with the fasting plasma glucose level(r=0.400 P<0,05 for E-selectin, r=0.456 P<0.01 for P-selectin). They were also positively correlated with the levels of serum triglyceride(r=0.531 P<0.01 for E-selectin, r=0.415 P =0.05 for P-selectin) but not with the levels of serum total cholesterol, LDL and HDL cholestrol in NIDDM patients. 3) No significant correlation was noted between the levels of E-selectin or P-selectin and the duration of NIDDM. And the levels were not different according to the type of treatment. 4) E-selectin level, not P-selectin level, was significantly higher in the patients with nephropathy when compared to the patients without nephropathy. But such difference was not noted when the patients were classified according to the presence of retinopathy or neuropathy. 5) E-selectin level was positively correlated with P-selectin level in both NIDDM patients and normal controls(r=0.52, P<0.01). CONCLUSION: These findings suggest that endothelial dysfunction, revealed by increased cellular adhesion molecules, could play a role in the pathogenesis of diabetic atherosclerotic vascular disorders in NIDDM patients with increased fasting plasma glucose control and hypertriglyceridemia. In addition, elevated soluble E-selectin and P-selectin level in blood might be used as a marker of diabetic nephropathy.

Soluble P-selectin, E-selectin, and VCAM-1 as Markers of Vascular Endothelial Damage in Diabetic Patients with Microangiopathy.: Young Sun Kim, Dong Won Byun, Kyo Il Seo, Myung Hi Yoo, Guk Bae Kim, Seong Soo Koong; Korean Diabetes J. 1998;22(1):35-46. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Vascular complications of diabetic patients are common and are known as the major cause of death. Hyperglycemia has been supposed to be the leading cause of vascular complications by unknown mechanisms. In recent reports, hyperglycemia stimulated the expression of leukocyte-endothelial adhesion molecules in the endothelial cells, and increased plasma concentrations of their soluble forms. The aim of this study was to evaluate the role of plasma concentrations of soluble P-selectin(sP-selectin), soluble E-selectin(sE-selectin), and soluble VCAM-1(sVCAM-1) in diabetic patients with microvascular complications as markers of vascular endothelial damage. METHODS: In this study, plasma levels of sP-selection, sE-selectin and sVCAM-1 were determined by ELISA in 39 diabetic patients and 25 normal conirols. RESULTS: The concentrations of sP-selectin, sE-selectin, and sVCAM-1 in diabetic group were significantly higher than those in control group. The concentrations of sP-selectin and sE-selectin decreased sigruficantly after contol of hyperglycemia in diabetic group, but sVCAM-1 level was not altered by treatment. In diabetic group with microvascular complications, the concentrations of sP-selectin and sE-selectin significantly were elevated as compared with the diabetic group without microvascular complication, but the concentration of sVCAM-l was not different between the two groups. In diabetic group, the levels of sP-selectin, sE-selcctin, and sVCAM-1 were not correlated with the concentration of C-peptide, HbA1, triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol. There was no difference between control group and diabetic group in terms of age and sex. There were not any differences of sP-selectin, sE-selectin, and sVCAM-1 concentration according to the duration of diabetes and the presence of hypertension. CONCLUSION: Hyperglycemia might stimulated the expression of P-selectin, E-selectin, and VCAM-1 in the endothelial cells and increased the plasma levels of their soluble forms. sP-selectin and sE-selectin could be used as indicators of ongoing vascular dysfunction in diabetes as well as a dynamic surrogate marker for the effectiveness of therapeutic interventions.

The Effect of Elevated Plasma Free Fatty Acids on Non-Insulin-Mediated Glucose Uptake and Insulin Resistance.: Yong Ki Min, Jong Ho Ahn, Jae Joon Koh, Hong Kyu Lee, Hun Ki Min; Korean Diabetes J. 1998;22(1):47-55. Published online January 1, 2001

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Abstract PDF: BACKGROUND
In vivo glucose uptake occurs via two mechanisms, namely insulin-mediated glucose uptake(IMGU) and non-insulin-mediated glucose up-take(NIMGU). NIMGU accaunts for about 70~85% of postabsorptive glucose uptake. Despite many studies, it is still controversial how an increase in lipolysis affects glucose metabolism in man. More specifically, the effect of free fatty acid(FFA) on NIMGU has not been exanuned. METHOD: Two-step(euglycemia- hyperglycemia) glucose clamp techique with [3-H]-glucose infusion was performed in 6 normal men. Each man was studied twice, with(test experiement) and without (control experiment) the administration of lipid and heparin at an interval of at least 4 weeks in random order. The subjects received an insulin infusion at 1.1 pmol/kg. min in conjuction with the infusion of somatostatin(step 1, 153 nmol/h; step 2, 458 nmol/h). Result: Plasma glucose levels during step 1 were 5.4+0.1 mmol/L(control experiment), 5.4+0.1 mmol/ L(test experiment), and were raised to 14.7+0.2 mmol/L, 14.6+0.1 mmol/L, respectively, during step 2. Plasma insulin levels during step 1 were 56+4 pmol/L(control experiment), 52+4 pmol/L(test experiment), and were 65+3 pmol/L, 62+4 pmol/L, respectively, during step 2. In control experiment, plasma FFA levels were 0.24+0.02 mmol/L during step 1 and 0.11+0.01 mmol/L during step 2. In test experiment, plasma FFA levels increased significantly to 1.08+0.06 mmol/L during step 1 and 1.01 +0.04 mmol/L during step 2, respectively(p<0.01). Glucose infusion rate(GIR) to increase glucose concentrations to the desired levels were 7.7+0.8 pnol/ kg,min during step 1 and 29.7+3.7 pmol/kg.min during step 2 in control experiment. In test experiment, GIR decreawd significantly to 3.8+0.9 pmol/ kg.min during step 1 and 20.7+1.2 pmol/kg.min during step 2, respectively(p<0.05). There was no significant difference between NIMGU, estimated by the difference between glucose disapperance rate of step 1 and step 2 of lipid infusion test experiment and that of control experiment. CONCLUSION: These results showed that artificial elevation of plasma FFA levels led to a state of insulin resistance, however, the change of FFA level did not influence NIMGU in man.

Decreased Mitochondrial DNA Content in Peripheral Blood Leukocyte procedes the Development of Type 2 Diabetes Mellitus.: Jae Joon Koh, Jong Ho Ahn, Soon Ja Kwon, Ji Hyun Song, Chan Soo Shin, Do Joon Park, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 1998;22(1):56-64. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Mitochondrial mutations and deletions, have been implicated in the pathogenesis of diabetes mellitus. This can explain only a very small proportion of the patients with diabetes mellitus. Mitochondrial DNA(mtDNA) is vulnerable to oxidative stress, resulting in both qualitative and quantitative changes. We reported that the amount of mtBNA decreased in the peripheral blood leukocyte of patients with NIDDM. In this study, we examined that decreased mtDNA content preceded the development of NIDDM{Non-insulin dependent diabetes mellitus) and correlated with various insulin resistance parameters.In this study, we demonstrated that the amount of mtDNA decreased in peripheral blood leukocyte of patients with NIDDM. Furthermore, we found that lower mtDNA levels preceded the development of diabetes mellitus. METHODS: We utilized the stored blood samples from two community-based survey conducted in Yonchon County, Korea in 1993 and 1995. We selected 23 newly diagnosed diabetic patients and 22 age- and sex-matched control subjects. The buffy coats of peripheral blood samples were used for the competitive PCR and the products pairs were separated by gel EP. The content of mtDNA was calculated with the densitometry. RESULTS: There were no difference in the initial anthropometric parameters, blood pressure and lipid profiles between subjects who became diabetic converters and non converters. The mean quantity of mtDNA was lower in the converters, with 102.8+ 41.5 copies/pg template DNA compared to 137.8+ 67.7 copies/pg template DNA of the controls(p 0.05). The significant inverse correlations were noted between mtDNA content and WHR(r=0.31, p<0.05) in the first, and fasting glucose level(r=-0.35, p<0.05), diastolic blood pressures(r=-0.36, p<0.05), and WHR(r=-0.40, p<0.01) in the second survey. The correlations with the serum levels of total and high density cholesterol, triglyceride, insulin and proinsulin were not statistically significant. CONCLUSION: Although a relationship between diabetes and mitochondrial dysfunction has been suspected. This study showed that decreased mtDNA content in peripheral blood proceded the development of NIDDM. This is the first study to demonstrate that quantitative changes in mtDNA precede the development of NIDDM.

Lipoprotein (a) Level and Vascular Complications in NIDDM.: Ji Youn Kim, Mung Su Kim, Joung Min Kim, Jai Hong Park, Joung Hun Lee, Seung Won Yang, Dong Jin Chung, Min Young Chung, Tai Hee Lee; Korean Diabetes J. 1998;22(1):65-73. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The risk of atherosclerosis is increased in subjects with diabetes mellitus. Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic vascular disease in subjects without diabetes. The contribution of Lp(a) to the increased risk for atherosclerosis and diabetic complications in subjects with diabetes is not well known. In this report we examined the relationship between Lp(a) levels and development of vascular (macro- and microvascular) complications, and the relationship between Lp(a) and other risk factors for vascular complications in subjects with non-insulin-dependent diabetes mellitus(NIDDM), METHODS: For this study we evaluated 152 patients with NIDDM(72 women and 80 men). Lp(a) level was measured with N-Latex Lp(a) Reagent. Electrocardiography, coronary angiography, brain CT/MRI, doppler velocimetry and peripheral angiography were done for diagnosis of macravascular complieations, and fundus camera, nerve conduction velocity, BBV (beat to beat variation), VPT(vibration perception threshold) and 24-hour urine protein amount were examined for diagnosis of microvascular complications. RESULTS: Lp(a) levels in subjects with ischemic heart disease, cerebrovascular disease and diabetic retinopathy were significantly higher than those in subjects without above mentioned diseases. ApoB/ApoA1 ratio and LDL-cholesterol levels in subjects with Lp(a) level>30mg/dL were significantly higher than those in subjects with Lp(a) level 30mg/dL, and Lp(a) has a positive correlation with ApoB/ApoA1 ratio and LDL-cholesterol in NIDDM patients with vasculopathy. CONCLUSION: These results suggest that high Lp(a) levels seem to be associated with macrovascular and microvascular(especially with retinopathy) complications in subjects with NIDDM and Lp(a) level should be measured in the NIDDM with high level of ApoB/ApoA1 ratio and/or LDL-eholesterol.

The Relationship between Salt Perception and Salt Intake in Diabetic patients.: Kye Young Huh, Il Suh, Kyung Rae Kim, Chung Mo Nam, Kyung Won Oh; Korean Diabetes J. 1998;22(1):74-83. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The increase of the prevalence rate of diabetes mellitus(DM) and its complications have become a public health problem in Korea. Especially, diabetic macrovascular disease and nephrosis preliminarily require the hypertension treatment which consists of reducing salt intake. Although the salt intake of diabetic patients is so important, there have not been sufficient studies on salt perception and salt intake of diabetic patients in Korea. The purpose of this study was to investigate the relationship between salt perception and salt intake in diabetic patients. METHODS: The materials used in this study were questionnaires, anthropometric measurement, laboratory data and medical charts. Eighty-seven diabetic patients were interviewed at the out-patient department of internal medicine in Yonsei Medical Center Youngdong Severance Hospital. RESULTS: Of these patients, salt intake which was estimated through 24-hour urinary sodium excretion was 16.6gm in men, 12.9gm in women. To the question, 'How much salt do you intake compared to common people?' 38% both men and women answered less. And to the question, Do you think that you should reduce your salt intake?' 55% of men and 33% of women answered 'No. To the question, Do you exert yourself to reduce your salt intake?, 66% of men and 68% of women answered 'Yes. And to the question, Can you reduce your salt intake?, 84% of men and 71% of women answered, Yes. And the major reason of being unable to reduce the salt intake was loss of taste. The relation of 24-hour urinary sodium excretion and duration of DM, the degree of DM control, and the practice of diabetic diet therapy were not significant. CONCLUSION: No significant correlation was found between salt perception and salt intake. Their willingness for the reduction of salt intake were not put into practice in rea1 situation. As a follow-up measure, the medical staff is required to continuously monitor and give feedback to correct the amount of salt intake of diabetic patients. Furthermore, it can be strongly suggested that salt intake reduction program with low salt recipes should be developed and implemented far diabetic patients. This, in conjuction with other therapies such as medical monitoring, will eventually achieve the reduction of salt intake in diabetic patients.

The Characteristics of Insulin-resistance Syndrome in the Korean Population.: Jin Sung Kim, Gun Sang Park, Yun Yong Lee, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Hyeon Kyu Kim, Yong Soo Park, Soon Ja Kwon; Korean Diabetes J. 1998;22(1):84-92. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Insulin-resistance syndrome or syndrome X which includes diabetes mellitus, hypertension, dyslipidemia, and obesity has been regarded as one of the mechanisms involved in the atherosclerotic disease. This study was performed to evaluate the prevalence of each camponent of insulin-resistance syndrome. We have also analyzed the clustering of insulin-resistance syndrome according to fasting insulin levels in subjects who participated in the Younchon county diabetes prevalence study in 1993. METHOD: One thousand, eight hundred and eleven subjects among 2520 subjects over 30 years-old were enrolled, We investigated the prevalence of 5 metabolic syndromes: glucose intolerance(impaired glucose tolerance and diabetes mellitus by WHO criteria), hypertension(diastolic blood pressure >95 mmHg), Hypertriglyceridemia(triglyceride >2.26 mmol/L), low HDL cholesterolemia(HDL cholesterol <0.91 mmol/ L) and obesity(body mass index >25 kg/m) according to fasting serum insulin level. RESULTS: The prevalence of glucose intolerance (diabetes mellitus and impaired glueose tolerance), hypertension, hypertriglyceridemia, low HDI, cholesterolemia and obestiy were 18.2%, 21.3%, 10.9%, 45.6% and 36.3%, respectively. According to the four quartiles(quartile 1, 2, 3, 4) of fasting serum insulin level, the prevalence rate of each metaboic syndrome was as follows: 9.5%, 15.6%, 22.8% and 25.0% for glucose intolerance; 18.7%, 17.5%, 21.1% and 27.9% for hypertension; 5.0%, 8.1%, 13 8% and 16.9% for hypertriglyceridemia; 37.9%, 46.6%, 46.5% and 51.6% for low HDL cholesterolemia; 19.2%, 30.1%, 40.8% and 55.4% for obesity. As the fasting insulin levels increase, the clustering of 2 or more disease increase. CONCLUSION: Metabolic syndromes associated with insulin-resistance are relatively common disorders in the Korean population. The prevalence and clustering of metabolic abnormalities also increase as serum insulin level increases in Korean population.

QTc Interval and QT Dispersion Prolongation in NIDDM Patients with Diabetic Autonomic Neuropathy.: Yong Kyun Cho, Seung Won Lee, Won Tae Seo, Yoon Sang Choi, Jin Ho Kang, Man Ho Lee, Sang Jong Lee; Korean Diabetes J. 1998;22(1):93-102. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It has been reported that QTc interval and QT dispersion prolongation on 12 lead EKG reflects predictability and diagnosis of cardiovascular complications induced by autonomic nervous system abnormalities. We have investigated in NIDDM patients whether severity of cadiovascular autonomic neuropathy(CAN) evaluated by conventional standard cardiovascular autonomic function test is correlated with prolongation of QT, QTc interval and QT dispersion. In addition, whether these prolonagtion can reflect CAN and if any other clinical variables related to pralongatian exist. METHODS: Eighty patients(39 male, 41 female) treated with oral hypoglycemic agents or insulin after diagnosis of NIDDM in our hospital were included in the study. These patients were devided into three groups (Group I, 13 subjects: No CAN, Group II, 20 subjects: Borderline CAN, Group III, 47 subjects: Definite CAN) according to the score of standard catdiovascular autonomic function test(Deep breathing test, Lying to standing test, Heart ration on Valsalva manuever, Postural BP drop test). The measured QT, QTc interval and QT disp rsion of eaeh diabetic group and control group were analyzed. RESULTS: l. Statistically significant prolongation of QT,QTc, QT dispersion was observed in NIDDM tients as compared with those of control group(p=0.015, 0,021, 0.001). 2. Severity of autonomic neuropathy has shown positive correlation with only prolongation of QT dispersion(p<0.05) in three diabetic subgroups. 3. Statistically significant difference was not ob::rved in HbAlc and BMI between each patients groups of NIDDM(p>0.05) but both HbAlc and BMI showed weak positive correlation with prologation of QT dispersion(r=0.262, r=0.267 repectively). CONCLUSION: QTc interval and QT dispersion are considered easily accessible factors to predict and evaluate the degree of cardiovascular autonomic function abnormalities in NIDDM patients, yet further long term follow up and study in large group should be carried out to decide if these factor can predict and reflect severity of cardiovascular abnormalities such as ventricular arrhythmia, and sudden cardiac death. In additian, prolonged QT dispersion has shown weak positive correlation with both HbAlc and BMI and some other influential factors are suggested to play a role in autonomic neuropathy in NIDDM patients.

A Case of Fibrocalculous Pancreatic Diabetes With Familial Tendency.: Chang In Kim, Myung In Lee, Dae Jun Lee, So Hee Son, Sook Hee Keun, Sang Jin Kim; Korean Diabetes J. 1998;22(1):103-109. Published online January 1, 2001

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Abstract PDF: Diabetes in tropical regions and in some developing countries presents clinically differently from IDDM and NIDDM in the Western world and developed countries. So, the WHO recognized malnutrition-related diabetes mellitus and subdivided into fibrcalculous pancreatic diabetes(FCPD) and protein-deficient pancreatic diabetes in 1995. While it appears that malnutrition may influence the expression of other types of diabetes, the evidence that diabetes can be directly caused by malnutrition is not convincing. Thus, at present time, FCPD is best considered as a secondary form of diabetes. FCPD is a form of diabetes with a high prevalence in tropical and developing countries, but rare in Korea. It occurrs in young indi.viduals, accompanied by pancreatic calculi and or ductal dilatation of unknown cause, and is ketosis-resistant. We experienced a case of FCPD with familial tendency and report with a brief review of the literature.

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