Diabetes & Metabolism Journal

Volume 21(1); March 1997

Original Articles

Diabetes Mellitus and Cognitive Dysfunction.: Min Young Chung; Korean Diabetes J. 1997;21(1):1-13. Published online January 1, 2001

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Abstract PDF: No abstract available.

Genetic Markers for IDDM.: Yong Soo Park; Korean Diabetes J. 1997;21(1):14-24. Published online January 1, 2001

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Abstract PDF: No abstract available.

Diabetes Mellitus and Endothelial Cell Dysfunction.: Doo Man Kim; Korean Diabetes J. 1997;21(1):25-28. Published online January 1, 2001

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Abstract PDF: No abstract available.

Plasminogen Activator Inhibitor ( PAI-1 ) Levels in Patients with non-insulin Dependent Diabetes Mellitus ( NIDDM ).: Hong Kyu Kim, Chul Hee Kim, Eun Sug Shin, Hyo Jung Kim, Joong Yeol Park, Sung Kwan Hong, Hyun Sook Chi, Ki Up Lee; Korean Diabetes J. 1997;21(1):29-38. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Conventional cardiovascular risk factors cannot fully explain high risk of cardiovascular disease in patients with non-insulin dependent diabetes mellitus(NIDDM). This study was undertaken to know whether plasma PAI-1 levels are increased in NIDDM patients, and to identify factors intluencing Pal-1 levels. METHODS: Forty three microalbuminuric, 41 normoalbuminuric NIDDM patients and 39 normal controls matched with age, sex and body mass index (BMI) participated in this study. Clinical characteristies and laboratory findings such as lipid profile, fasting serum C-peptide and PAI-1 levels were evaluated, RESULTS: NIDDM patients showed significantly higher PAI-1 levels than normal controls(44.3+17.4 ng/mL vs. 26.3+12.6ng/mL, p<0.05). However, we failed to show the differences in PAI-1 levels between NIDDM patients with microalbuminuria and normoalbuminuria. PAI-1 levels were significantly correlated to BMI, fasting plasma glucose, HbA1, triglyceride and serum C-peptide levels. Multiple regression analysis showed that serum triglyceride and fasting serum C-peptied levels were independently related to PAI-1 levels. Conclusion; These findings suggested that elevated PAI-1 levels may contribute to increased risk of cardiovascular disease in patients with NIDDM.

Significance of Serum Anticardiolipin Antibody in Non-Insulin Dependent Diabetes Mellitus.: Hee Jin Kim, Young Sun Hong, Yeon Ah Sung, Nan Ho Kyung; Korean Diabetes J. 1997;21(1):39-48. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The antiphospholipid antibodies have been characteristically found in the patients with autoimmune diseases. Some previous studies revealed that antiphospholipid antibodies are increased in the sera of patients with diabetes and correlate with the extent of neuropathy and measurements of amiphospholipid antibodies may constitute a marker for ongoing damage to nerves. We measured serum anticardiolipin antibodies(IgG, IgM) to assess the prevalence and significance of anticardiolipin antibodies in NIDDM patients. METHOD: Ninety NIDDM patients were screened for lgG/IgM isotypes of anticardiolipin antibodies by enzyme-linked immunosorbent assay and compared with 30 control subjects. RESULTS: 1) The titers and positivities of IgG anticardiolipin antibodies were significantly higher in the sera of NIDDM patients than those of control subjects(P<0.05). 2) In NIDDM patients with IgG anticardiolipin antibody, the titer of serum c-peptide was significantly lower(P<0.05) and the body mass index tended to be lower(P=0.08). 3) There were no significant differences of positivities of IgG anticardiolipin antibodies according to the state of chronic diabetic complications and the mode of treatment(P>0.05). 4) In the patients with NIDDM, no significant association was found between the titers of IgG anticardiolipin antibodies and age, diabetic duration, fasting blood glucose, HbAlc, total cholesterol and triglyceride. CONCLUSION: The titers and positivities of IgG anticardiolipin antibodies were elevated in NIDDM. In the NIDDM patients with IgG anticardiolipin antibody, the serum titers of c-peptide were significantly lower and the body mass index tended to be lower. It seems that serum IgG anticardiolipin antibodies might have autoimmune relationship with slowly progressive IDDM, but further prospective mass studies will be requird.

Plasma Endothelin in Patients with Non-Insulin Dependent Diabetes Mellitus: Plasma Endothelin according to Insulin.: Jae Ook Lee, Sung Ook Choo, Jang Gyu Lee, Mu Ryen Jun, Gyeng Hyen Park, Jun Tack Joo, Jin Kwan Lee; Korean Diabetes J. 1997;21(1):49-55. Published online January 1, 2001

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Abstract PDF: BACKGROUND
As a potent vasoconstrictor isolated from human and porcine vessels, endothelin(Et) is involved in the pathophysiology of various cardiovascular disease. Although the pathophysiological roles of Et in the patient of diabetes needs further investigation, many reports have shown the increased level of Et in the patient of diabetes. Insulin has also been found to play a role in the elevation of Et in vivo and expenmental study. The aim of our study v as not only to estimate the level of Et-1 in the patient of NIDDM and normal subjects but also compare it to the level of plasma insulin, C-peptide and complications of NIDDM. METHODS: Plasma Et-1 levels were measured in 49 patients of NIDDM and 26 normal subjects. All patients of diabetes were divided into 3 groups: group I(patients with no previous treatment), group II (patients with oral hypoglycemic agent), and group lII(patients with insulin therapy). Nerve conduction velocity and ophtha]moscopic examination was done in all pertinent patients, Plasma Et was determined by RIA after extraction with an Prep Sep-Pac C-18 cartilidge. RESULTS: Plasma Et-1 level of the patient of each group and control subject was shown in Table 1. Plasma Et-1 level of the patient of NIDDM was 3.65 +2.05pmol/mL, which was not statistically different from that of control group(2.80+2.07, p=0.105). No significant correlation of plasma Et level with HbAlc, duration of diabetes, triglyceride and cholesterol in the patient of NIDDM was observed(p>0.05). There was not any significant correlation between plasma Et level and complications of diabetes. Such as angiopathy, microalbuminuria and neuropathy. Even through the insulin and Et level seems to he elevated in group III but it is statistically not significant(p>0.05). CONCLUSIONS: Our study suggests that the patient of NIDDM and normal subject statistically show no difference in the level ot Et although there appear slightly high value in the patient group. Any positive correlation is not found between the Et level and those factors such as angiopathy, microalbuminuria and neuropathy. In conclusion futher investigation is needed to clarify the role of Et in the patient of NIDDM.

Disturbance of Cutaneous Microcirculation assessed by Laser Doppler Flowmetry in Non-Insulin Dependent Diabetic patients.: Jeong Hyun Park, Sang Hee Nam; Korean Diabetes J. 1997;21(1):56-64. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetic microangiopathies are well-known long-term complication of diabetes mellitus, These are wide-spread phenomena, but little is known about the nature of cutaneous microcirculatory disturbance in diabetic patients which could be considered as cutaneous diabetic microangiopathy. To assess the cutaneous microcirculatory disturbance of diabetic patients, we performed this study. METHODS: We performed the laser Doppler flowmetry which has been known to be an accurate device for measuring cutaneous microcirculatory blood flow to 14 control subjects and 16 non-insulin dependent diabetic patients. We used thermal reactive hyperemic technique to the dorsum of right index finger and right great toe for measuring both baseline and maximum cutaneous microcirculatory blood flow. RESULTS: The baseline microcirculatory blood flow measured at 35C did not show any statistically significant differences between control subjects and diabetic patients, on both finger dorsum and toe dorsum. The maximurn microcirculatory blood flow measured at 44C showed statistically significant difference between control subjects and diabetic patients only at toe dorsum, but not at finger dorsum (p<0.05). CONCLUSION: From the above results, we conclude that cutaneous microcirculation is disturbed in noninsulin dependent diabetic patients, which was manifested at the toe dorsum in the condition of maximum blood flow induced by thermal stimulation. Further studies an exact pathophysiology and possible correlations with diabetic microangiopathies, diabetic duration and the level of glycemic control are needed along with more refinement of measurement techniques.

A Study on the Patterns of Clinical Characteristics according to Body Weight and Weight Changes in Korean NIDDM Patients.: Young Sun Hong, Hee Jin Kim, Yeon Ah Sung, Nan Ho Kyung; Korean Diabetes J. 1997;21(1):65-73. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It is known that Korean NIDDM patients are mainly non-obese and have experienced weight loss frequently during the course of the disease. However, there have been few studies about the patterns of treatment and complications according to the weight changes, Our purpose was to determine the characreristics of diabetes in Korea by examining the differences in the clinical features according to the current weight and the weight changes. METHODS: From 308 Korean NIDDM patients. We obtained the data about the weight at the time of maximal obesity and diagnosis of diabetes and measured the current weight and height. We also evaluared the presence of diabetic retinopathy, nephropathy and neuropathy, We designated the patients with BMI 21kg/m and less as the lean group, the patients with BMI 21 to <26kg/m as the middle-range group and the patients with 26kg/m and over as the obese group. RESULTS: At the time of maximal weight, 61.4% of the patients were obese, but 40.3% were obese at diagnosis and only 33.8% were obese at recruitment. In the lean group, C-peptide was low and the frequency of insulin therapy was high. Although there was no statistical significance, diabetic complications were more frequent in the lean group. The percentage of the patients who lost weight (loss of 10% trom the maximal weight) was 65.9% in the lean group, 42.3% in the middle-range group and 32.7% in the obese group. The prevalence of retinopathy and neuropathy were higher in the group with weight loss, although not significantly. CONCLUSION: Of 308 NIDDM patients, 42.2% experienced weight loss before and after the diagnosis and only 33.8% were obese at recruitment. In the lean group, insulin secretory capacity was low and the frequency of insulin therapy was high. Our study showed that the lean group and the patients who have lost weight tended to have higher prevalence of the complications. The mass prospective study about the clinical characteristics according to weight changes in Korean NIDDM patients would be needed.

Venous Oxygenation in the Feet of Diabetics with Neuropathic foot Ulceration.: Chung Gu Cho; Korean Diabetes J. 1997;21(1):74-81. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetic patients with non-infected neuropathic foot lesions frequently have prominent pedal arteries and distended dorsal foot veins, both in the ulcerated and in the non-ulcerated foot. Such patients also have increased blood flow in the lower limbs as suggested by plethysmographic and ultrasound studies. Accordingly, the aim of this study was to evaluate the venous oxygenation, as determined by partial pressure of oxygen(PO), in the feet of diabetics with and without foot ulceration and neuropathy in order to confirm the arteriovenous(A-V) shunting in the diabetic neuropathic foot may be important in the pathogenesis of ulceration. METHODS: Venous PO was measured in the feet and hands of four subject groups: 8 diabetics with neuropathy and foot ulceration(group 1); 10 diabetics with neuropathy but no ulceration(group 2); 10 diabetics with no evidence of neuropathy(group 3); and 9 non-diabetic controls(group 4). After an initial 30-min period of stabilization, veins on the dorsum of each foot and on the back of the hand were cannulated using a Butterly infusion set, 0.8mm gauge. Blood was withdrawn from each site into a heparinized glass syringe for immediate analysis of PO using a blood gas analyser. RESULTS: The mean venous PO2 in the feet of diabetic subjects with neuropathy and foot ulceration (group 1: 60.7+6.3mmHg)was significantly higher than in controls(group 4: 44.3+6.0mmHg) or the other two diabetic groups(group 2: 52.3+9.0mmHg, group 3: 46.1+5.5mmHg). Venous PO2 in the feet of the diabetic subjects with ulcers was also significantly higher than in their hands(45.4+5.8mmHg) or in the hands of the other groups(group 2:.46.6+6.3mmHg, group 3: 44.5+4.9mmHg, group 4: 44.9+5.1mmHg). CONCLUSION: These results provide further evidence of abnormal blood flow in the diabetic neuropathic foot and are compatible with arteriovenous shunting.

Relationship between Cardiovascular Autonomic Neuropathy and Diabetic Retinopathy in Patients with Non-Insulin Dependent Diabetes Mellitus.: Jae Chun Lee, Sang Yob Nam, Ji Sung Yoon, Jin Chul Park, Kyu Chang Won, Ihn Ho Cho, Hyoung Woo Lee, Hyun Woo Lee; Korean Diabetes J. 1997;21(1):82-90. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The presence of cardiovascular autonomic neuropathy may play a permissive role in the development and progression of diabetic retinopathy. But, there is little information regarding the degree of association between the progression of diabetic retinopathy and cardiovascular autonomic neuropathy in patients with non-insulin dependent diabetes mellitus. Thus, this study defined the relationship between the progression of diabetic retinopathy and cardiovascular autonomic neuropathy in patients with non-insulin dependent diabetes mellitus. METHODS: Seventy-nine patients with non-insulin dependent diabetes mellitus were separated into 2 groups based on the presence of cardiovascular autonomic neuropathy. Age, body mass index, duration of illness, plasma creatinine, BUN, fasting plasma glueose, glycated hemoglobin, lipid profile and 24hr urine total protein were not statistically different among the two groups. According to indirect ophthalmoscopy, patients were also classified as having proliferative, non-proliferative or no retinopathy. RESULTS: The results showed a striking relntionship between cardiovascular autonomic neuropathy and proliferative diabetic retinopathy(p<0.01). Corrected QT interval was more prolonged in non-insulin dependent diabetes mellitus patients with cnrdiovascular autonomic neuropathy than patients without cardiovascular autonomic neuropathy(p<0.05). In non-insulin dependent diabetes mellitus patients with cardiovascular autonomic neuropathy, there was no relationship between the prolongation of corrected QT interval and proliferative diabetic retinopathy, and there was no significant relationship between each of 5 components of cardiovascular autonomic neuropathy test and proliferative diiabetic retinopathy. CONCLUSION: These results suggest that the presence of cardiovascular autonomic neuropathy is strongly associated with proliferative retinopathy in patients with non-insulin dependent diabetes mellitus. But, long-term prospective studies on large cohorts of patients must be done to evaluate if cardiovascular autonomic neuropathy would be a risk factor or a risk indicator of an etiologic process underlying the development of proliferative retinopathy.

Analgesic Effects of DA-5018, a New Capsaicin Derivative, in Hyperalgesia of Experimental Diabetic Neuropathy.: Eun Ju Bae, Soon How Kim, Moon Ho Son, Hee Kee Kim, Myeong Soo Shin, Hyun Ji Kim, Won Bae Kim; Korean Diabetes J. 1997;21(1):91-101. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Painful peripheral neuropathy is one of the most common complications of diabetes and not responsive to conventional analgesics. Capsaicin cream has been used to treat the pain associated with diabetic neuropathy, rheumatoid arthritis, osteoarthritis and postherpetic neuralgia. But its common side effect, burning sensation, limits the use of it. DA-5018 is a newly synthesized capsaicin derivative which shows more potent systemic and topical analgesia than capsaicin in various animal models of acute and chronic pain, but has little skin irritaion. This study was designed to evaluate the effect of DA-5018 administered systemically or topically on hyperalgesia in streptozotocin-induced diabetic and galactosaemic rats. METHODS: One group of SD rats was treated with streptozotocin(60mg/kg, I.v.) and the pain thresholds were determined weekly by Randall-Selitto paw pressure test. And the other group of SD rats was maintained on 50%-galactose diet until 4~5 weeks and the pain thresholds were determined as well, Drugs were administered subcutaneously once a day for 7 days or topically to the paw for 5 hours a day for 10 days at a time when the hyperalgesia was already present. The increase of pain thresholds by drug was regarded as an indication of analgesia. RESULTS: Streptozotocin-diabetic rats displayed a reduction of pain threshold. Similarly, galactosefeeding resulted in significant reduction of pain threshold. It is concluded that hyperalgesia is a constant feature of sensory dysfunction in experimental models of diabetic and nutritional neuropathy. DA-5018(0.2, 0.5mg/kg, s.c.) produced significant antinociception with efficacy similar to that of capsaicin(10mg/kg, s.c.) in streptozotocin-induced hyperalgesia and furthermore, no tolerance developed for 7 days. And this analgesic effect was superior to desipramine(10mg/kg, s.c.). But ketoprofen(10mg/kg, s.c.) produced no analgesia. Topically, 0.3% DA-5018 cream was as effective as Zostrix-HP(capsaicin 0.075%) both in streptozotocin-diabetic and galactosefed rats while Kenofen gel(ketoprofen 3%) was ineffective to reduce pain. CONCLUSION: These results demonstrate the potent analgesic efficacy of DA-5018 in diabetic pain models and suggest that topical DA-5018 cream may relieves pain caused by diabetic neuropathy offering an alternative for patients not responsive to other treatments or unable to tolerate capsaicin.

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