Diabetes & Metabolism Journal

Volume 23(4); August 1999

Original Articles

Fetal Hyperinsulinemia and Ultrasonographic Measurement of Fetal Growth in Pregnancy Complicated by Gestational Diabetes Mellitus.: In Kwon Han, Chang Hoon Yim, Ho Yeon Jeong, Hak Chul Chang, Ki Ok Han, Hyun Ku Yoon, Park Jeong Eun, Soo Young Lee, Young Ho Lee; Korean Diabetes J. 1999;23(4):506-517. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Recently we reported that the large for gestational age (LGA) fetus of women with gestational diabetes mellitus (GDM) had disproportionate growth characterized by larger abdominal circumference (AC) but similar biparietal diameter (BPD) at third trimester compared to the fetus of normal pregnant women. The AC of LGA fetus appeared to be accelerated after 33 weeks gestation, and measurement of AC could be an effective method for prediction of LGA. Thus this study was performed to find the relationship between fetal hyperinsulinemia and disproportionate growth and to find the highly sensitive index for prediction of LGA infant in GDM. METHODS: We prospectively studied ultrasono- graphic growth patterns at 30, 34, 38 gestational weeks in 20 women with GDM and 15 normal pregnant women. The ultrasonographic measurements of fetus included biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), mid-thigh circumference (MTC), mid-upper arm circumference (MUAC), mid-thigh subcutaneous fat thickness (MTFT), mid-upper arm subcutaneous fat thickness (MUAFT), fetal liver length (FLL), chest circumference (CC) and heart circumference (HTC). RESULTS: Compared to the fetus of normal pregnant women and appropriate for gestational age (AGA) fetus of GDM, LGA fetus of GDM had thicker MUAFT (3.9+0.9, 5.0+1.1, 5.6+1.7 mm, p=0.008) at 34 weeks, MUAFT (5.3+0.8, 5.6+0.9, 7.2+1.4 mm p=0.045) at 38 weeks and MTFT (5.2 +1.1, 5.5+0.8, 7.1+1.5 mm, p=0.019) at 38 weeks. They also had longer MUAC (120.3+9.9, 119.4+ 8.3, 138.7+11.2 mm, p=0.020) and CC(322.6+11.7, 324.4+15.7, 351.7+15.0mm, p=.025, respectively). There was a positive correlation between umbilical venous C-peptide concentration and birthweight (r=0.626, p=0.005) and symmetry index (r=0.523, p=0.03) of newborns. There was also a positive correlation between C-peptide concentration and MUAC (r=0.449, p=0.038) and MUAFT (r=0.426, p=0.045) in GDM group. CONCLUSION: The LGA fetus of women with GDM showed an accelerated growth of predominantly subcutaneous fat tissues that should be caused by the fetal hyperinsulinemia. Ultrasonographic measurement of subcutaneous tissues may be the most sensitive index for prediction of growth abnormalities in GDM at late gestation.

Effect of Transforming Growth Factor-B1 and Platelet Derived Growth Factor on Synthesis and Gene Expression of Collagen and Non-Collagen Protein in Aortic Smooth Muscle Cells Cultured in Different Concentrations of Insulin and Glucose.: Kun Young Sohn, In San Kim, Bo Wan Kim, Jung Guk Kim, Sung Woo Ha, Jick Hwa Nam, Seong Mo Koo, Rang Woon Park, Sam Kweon; Korean Diabetes J. 1999;23(4):518-529. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The mechanism for accelerated atberosclerosis in diabetes mellitus is unclear although diabetes mellitus is associated with substantial increase in prevalence of atherosclerotic disease. Extracellular matrix formation by vascular smooth muscle cells has been accepted as playing important roles during development of atherosclerosis. High glucose condition has been reported to increase the synthesis of extracellular matrix such as collagen and fibronectin in cultured mesangial cells. Insulin and some cytokines such as TGF-B and PGF have also been reported to stimulate the synthesis of collagen in mesangial cells. So we studied the effect of high glucose, insulin, TGF-Band PDGF on vascular smooth muscle cells. METHODS: To determine the effect of bigh glucose condition on collagen synthesis in vascular smooth muscle cells, cells were grown in the culture medium containing either normal (5.5 mM) or high (25 mM) glucose. And we used several concentrations of TGF-B1PDGF-BB and insulin in order to determine the synergistic effects of collagen synthesis and type I collagen mRNA expression. RESULTS: We observed that cells cultured in high glucose media synthesized more collagen and increased expression of type I collagen mRNA as compared to normoglycemic media. The amount of synthesized collagen and type I collagen mRNA expression increased proportionally to the increase in insulin concentration. There was no relationship of TGF-B1or PDGF-BB with the expression of type I collagen mRNA but these cytokines stimulated the synthesis of collagen and noncollagen protein. There was no synergistic effect of col)agen synthesis and type 1collagen mRNA expression by high glucose, insulin, and cytokines. CONCLUSION: These results suggest that TGF-Band PDGF may not influence type I collagen mRNA expression under hyperglycemia or hyperinsulinemia in vascular smooth muscle cells. Further studies about the other types of collagen expressions such as type IV, and V are needed because TGF-Band PDGF stimulated the synthesis of collagen and noncollagen protein.

Protective Mechanism of Glucose against Alloxan-Indeved HIT-T15 Cell Damage.: Tai Hee Lee, Tae Sun Park, Hyung Rho Kim; Korean Diabetes J. 1999;23(4):530-540. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Glucose prevents the development of alloxan-induced diabetes, but the precise protective mechanism of glucose is not yet clearly known. METHODS: The protective mechanism of glucose on alloxan-induced B-cell damage as investigated using a Syrian hamster transformed B-cell line,HIT-T15 cells. RESULTS: Alloxan caused cell death, inhibition of insulin release, elevation of cytosolic free Ca, DNA fragmentation and decrease of cellular NAD+and ATP. However, pretreatment of HIT-T15 ce]ls with glucose significantly blocked DNA fragmentation, depletion of intracellular NAD+,ATP and cell viability induced by alloxan, but did not affect the increase of cytosolic free Ca2+.The result indicate that glucose acts between Ca2+ influx and DNA fragmentation on a chain of reactions in the diabetogenesis of alloxan. CONCLUSION: These protective effects of glucose on alloxan-induced B-cell damage werepletely abolished by pretreatment with inhibitors of glucose-6-phosphate dehydrogenase, dehydroepian- drosterone (DHEA) and epiandrosterone (EPI), suggesting that a metabolic intermediate, such as NADPH, produced from glucose through pentose phosphate pathway plays an important role in the protection of B-cell damage by alloxan.

Prevalence of Islet Cell Autoantibodies and Mitochondrial DNA Mutation among Typical and Atypical Type 1 Diabetic Patients in Korea.: Hong kyu Lee, Kee Up Lee, Sung Kwan Hong, Byuong Doo Rhee, Dong Seop Choi, Hyoung Woo Lee, Sang Wook Kim, Hee Jin Kim, Nan Hee Kim, Kyong Soo Park, Woo Je Lee, Kyung Soo Ko; Korean Diabetes J. 1999;23(4):541-551. Published online January 1, 2001

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Abstract PDF: BACKGROUND
American Diabetes Association (ADA) proposed new criteria for the classification of diabetic patients, which were mainly based on the presence of autoimmune markers. But it is questionable if we can apply the new ADA criteria to Korean type 1 diabetic patients directly. In this study, we measured several autoantibodies to islet cell in Korean subjects with typical and atypical clinical manifestations of type 1 diabetes mellitus. And mutation of mitochondrial DNA was analyzed in the same patients. METHODS: We measured fasting serum C-peptide in 1870 diabetic patients attending the diabetes clinic of Asan Medical Center. Among the 117 patients with fasting serum C-peptide less than 0.6 ng/mL, glucagon-stimulated C-peptide was measured, and 57 Patients showed the level less than 1 ng/mL and they were diagnosed as type 1 diabetic patients. They were subgrouped into typical (n=26, needed insulin injection within 1 year after diagnosis) and atypical (n=30, did not need insulin for more than l year after diagnosis) type 1 diabetic patients. ICA was measured by indirect immunofluorescence method. Anti-GAD antibody was measured by radioimmunoassay. Anti-ICA512 antibody was measured by western blotting. Mitochondrial DNA 3243 mutation was detected using restriction enzyme Apa-I digestion of the amplified genomic DNA from the subjects. RESULTS: 1) Median age of onset was 40 years for atypical type 1 diabetes patients, while it was 27.5 years for typical type 1 diabetes patients. Average duration of insulin requirement was 0.18 years for typical group and 5.73 years for atypical group. In this series, only typical type 1 diabetic patients experienced diabetic ketoacidosis. 2) Only 50 % of typical type 1 diabetic patients and 47 % of atypical type 1 diabetic patients had at least one autoantibody among ICA, anti-GAD antibody and anti-ICA512 antibody. 3) Mitochondrial DNA 3243 point mutation was detected in 3 patients with atypical type 1 diabetes (10 %), but it was not found in patients with typical type 1 diabetes. CONCLUSION: These results suggest that the prevalence of autoantibodies in Korean type 1 diabetic patients was lower than that reported in Caucasians irrespective of clinical features. Therefore, it may not be easy to apply this new diabetes classification of ADA to Korean type 1 diabetic patients. In addition, mitochondrial DNA mutation may be responsible for some of the Korean atypical type 1 diabetic patients.

Relationship between Plasminogen Activator Inhibitor-1 (PAI-1), Lipoprotein(a) and Diabetic Retinopathy in Type 2 Diabetes Mellitus.: Shin Young Choi, Eun Young Kim, Kyung Won Kim, yu Young Jung, Jung Ho, Young Hun Ku, Hyung Kul Lee, Mi Kyung Kim; Korean Diabetes J. 1999;23(4):552-561. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetic retinopathy is a major cause of visual loss today, especially in diabetic patients having disturbances in hemostasis. Plasma plasminogen activator inhibitor-1 (PAI-1) and lipoprotein (a) may be involved in the pathogenesis of diabetic retinopathy of type 2 diabetes mellitus. This study was undertaken to determine whether plasma PAI-1 and Lp(a) levels are increased in type 2 diabetic patients with retinopathy, and to identify factors influencing PAI-1 and Lp(a) levels. METHODS: A total of 177 type 2 diabetic subjects were classified by the presence or absence of retinopathy, 92 and 85, respectively, and fasting blood samples were taken for assay of PAI-1, Lp(a), creatinine clearance, serum lipid profiles and C-peptide levels. RESULTS: Subjects with retinopathy showed higher levels of PAI-1 (p<0.05), Lp(a) (p<0.01), total cholesterol (p<0.01), triglyceride (p<0.01) and longer disease duration than those without retinopathy. In multiple regression analysis, PAI-1 levels were significantly correlated with high density lipoprotein (HDL) cholesterol, while Lp(a) levels were correlated with body mass index, total cholesterol and low density lipoprotein (LDL) cholesterol. CONCLUSION: These results suggest that elevated PAI-1and Lp(a) are associated with the presence of diabetic retinopathy.

Comparisons between Several Neurologic Tests of Large Myelinated Nerves in Type 2 Diabetic Patients with Peripheral Polyneuropathy.: Bo Wan Kim, Dong Hee Kim, Jung Guk Kim; Korean Diabetes J. 1999;23(4):562-574. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Neuropathy is the most common complication of diabetes mellitus but the prevalence is variable because there are many neurologic tests and criteria for diagnosis of neuropathy. Subjective symptoms of patients alone are not accurate for diagnosis of neuropathy, so objective sensory tests must be added. There have been few studies about correlation between each neurologic tests; furthermore there have been no studies on comparisons between each neurologic test in Korean diabetic patients. METHODS: From September 1997 to June 1998, 142 type 2 diabetic patients visited Kyungpook National University Hospital and included in this study. Every patient had nerve conduction study and vibration threshold test, pressure threshold test of 1 point and 2 point touch stimuli by pressure specified sensory device. Some of these patients had 10g monofilament test. From receiver operating characteristics curve, sensitivities of each test were calculated and compared with each test. RESULTS: 1. From receiver operating characteristics curve, when specificities of each test reached 90%, sensitivity of vibration perception threshold test of left great toe was 69.2 %, one point discrimination touch threshold test of left great toe was 50 %, and two point test was 31.6 %. Sensitivity of 10 g monofilament test was 57% and specificity was 85%. 2. Comparisons between each component of nerve conduction study and other neurologic test showed conduction velocity and amplitude were highly correlated with vibration perception threshold test, but F wave latency was highly correlated with one point discrimination threshold test. CONCLUSION: We though vibration perception threshold, lOg monofilament and quantitative sensory tests is adequate, simple and convenient tests in order to diagnose peripheral polyneuropathy. Of all these tests, vibration perception threshold was most useful as well as a sensitive test for screening and diagnosis of peripheral polyneuropathy in nan-insulin dependent diabetic patients.

Clinical Manifestation and Prognostic Factors in Nonketotic Hyperosmolar Coma.: Bo Wan Kim, Jung Guk Kim, Sung Woo Ha, Hyun Jeong Lee, Jeung Hun Han, Sang Won Jung, Jick Hwa Nam, Si Hyung Park, Soon Hee Lee; Korean Diabetes J. 1999;23(4):575-584. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Nonketotic hyperosmolar coma is usually a complication of non-insuli#n dependent diabetes and a syndrome of profound dehydration, hyperglycemia and hyperosmolarity. Therefore the patients present a progressive mental change. We evaluated the clinical manifestations of nonketotic hyperosmolar coma to assess the correlation between initial clinical manifestations and responses to treatment in patients with nonketotic hyperosmolar coma. METHODS: We studied 31 patients who had experienced proven nonketotic hyperosmolar coma at Kyungpook National University Hospital from March 1987 to February 1998. We divided nonketotic hyperosmolar coma patients into two groups, tbe complete recovery group and the incomplete recovery group, and compared clinical features and laboratory findings between these two groups. RESULTS: l) A total of 31 patients were studied. Eighteen patients were in the complete recovery group and thirteen patients were in the incomplete recovery group. 2) Mean age was 63.1+10.1 years old, initial blood glucose was 781.8+314.3 mg/dL, effective osmolarity was 342.6+34.9 mosm/L, arterial pH was 7.34. Serum creatinine level was 241.7+130.0 uol/L and BUN was 23.1+12.5 mmol/L. 3) Among clinical features of both groups (complete recovery and incomplete recovery groups), initial systolic blood pressure was 131.4+26.1 mmHg and 104.1+28.6 mmHg, diastolic blood pressure was 90.6+16.5 mmHg and 63.2+17.4 mmHg, and mean arterial blood pressure was 104.2 +18.2 mmHg and 76.8+19.7 mmHg. They revealed a significant difference statistically. 4) Arterial blood pH was 7.40 and 7.25, BUN was 18.4+11.7 mmol/L and 29.5+11.1mmol/L, and WBC count was 13850+4122/ mm and 19823+ 5946/mm. They revealed a significant difference statistically. 5) We also analyzed the significant factors together using multivariate logistic regression analysis. The only significant independent factor responsible for prognosis of nonketotic hyperosmolar coma was initial mean arterial blood pressure. CONCLUSION: Nonketotic hyperosmolar coma occurred more frequently in patients who were older and had abnormal renal function. The prognosis of patients was related with mean arterial blood pressure independently. Mean arterial blood pressure thought to be related to intravascular volume and arterial hypotension seems to reflect dehydration state. In conclusion, prevention and rapid correction of hypotension due to dehydration in older diabetics is the most important treatment to improve the prognosis.

Clinical Study on Cerebral Infarction Complicated with CIDDM pateints.: Sang Jong Lee, Yoon Sang Choi, Seong Chun Shim, Hi Moo Lee, Kwon Choi, Hwa Young Lee; Korean Diabetes J. 1999;23(4):585-591. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetes mellitus increases the risk of cardiovascular disease by two-fold and ischemic cerebrovascular disease by two to four-fold compared with the risk for non-diabetic patients. In patients with NIDDM, the risk of athero- thromboembolic cerebral infarction is known to be increased. We evaluated the significance of clinical variables with respect to the risk of cerebral infarction in NIDDM patients. METHODS: We assessed clinical variables retrospectively in 170 patients (90 men, 80 women) from April 1, 1991 through March 31, 1996, divided into 3 groups;100 NIDDM patients with cerebral infarction (58 men, 42 women), 40 NIDDM patients (17 men, 23 women) and 30 non-diabetic patients with cerebral infarction(15 men, 15 women). We evaluated 130 patients with cerebral infarction employing brain CT or MRI. RESULTS: 1) The mean values of age, serum total cholesterol, LDL, TG, HbA1C, systolic and diastolic BP were significantly higher in patients with NIDDM complicated by cerebral infarction than in those without cerebral infarction. 2) There were no statistically significant differences in body mass index (BMI), duration of DM and HDL between the two groups, respectively. 3) Diabetic retinopathy (especially, proliferative retinopathy) andmacroproteinuria(550 mg/day) were found significantly higher in diabetic patients with cerebral infarction than in those without cerebral infarction. 4) Multiple lacunar infarctions were more frequently observed in patients with NIDDM than non-diabetic patients with cerebral infarction. However, there were no statistically significant differences between the two groups. Conclusion: We suggest that increased age and HbAlC, hypertension, dyslipidemia, macroproteinuria and proliferative diabetic retinopathy could be associated with the risk of cerebral infarction in patients with NIDDM. The results showed that multiple lacunar infarctions were more frequent in patients with NIDDM than in non-diabetic patients. However, there were no statistical significances between the two groups.

Leptin Concentration in Diabetin and Non-diabetin Subjects in the Community Population.: Kee Up Lee, Seong Kwan Hong, Sang Wook Kim, Young Il Kim, Yun Ey Chung, Moo Song Lee, Joong Yeoul Park, Jin Yup Kim; Korean Diabetes J. 1999;23(4):592-600. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It has been suggested that adipose tissue releases leptin, a satiety factor, which circulates in blood and acts on the hypothalamus to suppress appetite. However, serum leptin concentration in obese human subjects is higher than that in lean subjects, suggesting leptin resistance. Although there have been several studies investigating serum leptin concentrations in Korean subjects, there has been no population-based study. This study was undertaken to investigate serum leptin concentration and associated factors in diabetic and non-diabetic subjects living in a rural area of Korea. METHOD: Among 898 subjects originally included in the Jung-up epidemiologic study, 119 men and 124 women with varying degrees of glucose tolerance were randomly selected. Serum leptin concentration was measured by radioimmunoassay. RESULTS: In agreement with previous studies, women had significantly higher serum leptin concentration than men. Serum leptin concentration in Korean men and women was apparently lower than in other populations, even after adjustment for BMI. Leptin concentration was not different among the three groups of glucose tolerance (normal glucose tolerance, impaired glucose tolerance and diabetes). Serum leptin concentration was positively correlated with serum true insulin, proinsulin and BMI in non-diabetic subjects. Serum leptin concentration was also significantly related with serum proinsulin/true insulin ratio in non-diabetic women. CONCLUSION: Serum leptin concentration in Korean subjects was lower than that reported in other populations. Serum leptin concentration was associated with BMI, serum true insulin and proinsulin levels in non-diabetic subjects, but not in diabetic ubjects.

Effect of Various Snacks and Meal woth Different Kinds of Staples on Bloos Glucose, Insulin, and C- Peptide Levels in Healthy and Type 2 Diabetic Patients.: Youn Sang Oh, Hye Ok Lee, Ryo Won Cho; Korean Diabetes J. 1999;23(4):601-612. Published online January 1, 2001

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Abstract PDF: BACKGROUND
There are large differences in the glycemic response among different foods. These differences complicate the glycemic response of foods in diabetic patients. Studies have found that the diet with low glycemic index foods had positive effects on the clinical management of diabetic and hyperlipidemia patients. The concept of glycemic index of foods and the values of glycemic index of meals were measured in this study to suggest the dietary recommendation for type 2 diabetic patients. METHODS: The blood levels of glucose, insulin, C-peptide were measured for healthy subjects and Type 2 diabetic patients after taking various foods and meals. The isocaloric glycemic index of each food and meal was calculated in comparison with standard foods and meals. RESULTS: For the normal subjects, serum glucose, insulin, and C-peptide reached peaks 30 minutes after the meals. The glycemic indices of red bean bread (122.2%),orange juice (106.8%), ice cream (106.3%), and yoghurt (101.6%) were the highest among the respective groups. For the Type 2 diabetic patients, serum glucose reached peaks 60 minutes after the ingestion of meals. The isocaloric glycemic indices were red bean (93.7%), barley (94.6%), mixed cereal (97.9%), Brown rice (98.8%), rice (100%), and milled foxtail (106.9%) in increasing order. CONCLUSION: It is expected that isocaloric glycemic index of Korean foods and meals that are most frequent]y and preferentially eaten by diabetic patients can be used as a guide for menu selection and also to educate the dietary guideline for diabetic patients.

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