Diabetes & Metabolism Journal

Original Article

Serum Cystatin C Reflects the Progress of Albuminuria: Jeong Seon Yoo, Young Mi Lee, Eun Hae Lee, Ji Woon Kim, Shin Young Lee, Ki-Cheon Jeong, Shin Ae Kang, Jong Suk Park, Joo Young Nam, Chul Woo Ahn, Young Duk Song, Kyung Rae Kim; Diabetes Metab J. 2011;35(6):602-609. Published online December 26, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.6.602

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Background

Research on the relationship between urinary albumin excretion and serum cystatin C in diabetes is restricted to cross-sectional studies. In this study, we investigated how well serial measurements of serum cystatin C level reflect changes in the urinary albumin excretion rate.

Methods

We enrolled and retrospectively collected data on 1,058 participants with type 2 diabetes who were older than 18 years and who had more than 3 years of follow-up with serial measurements of albuminuria and serum cystatin C at an outpatient clinic.

Results

With the use of a linear mixed model, we found that the albuminuria level for each patient over time corresponded with the annual change in serum cystatin C-based estimated glomerular filtration rate (cysC-eGFR) but did not correspond with the creatinine-based eGFR calculated by the modification of diet in renal disease formula (MDRD-eGFR). The discrepancy in the direction of the trend was smaller with cysC-eGFR than with MDRD-eGFR.

Conclusion

Serum cystatin C level reflects the trend in albuminuria level more accurately than serum creatinine level in Korean type 2 diabetes mellitus patients.

Citations

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Assessment of Cystatin C and Microalbumin as Biomarkers for Nephropathy in Patients with Type 2 Diabetes Mellitus
Bhuneshwar Yadav, Shashidhar K.N, Raveesha A, Muninarayana C.
Journal of Evolution of Medical and Dental Sciences.2021; 10(25): 1866. CrossRef
Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease
Eugene Han, Mi Kyung Kim, Byoung Kuk Jang, Hye Soon Kim
Diabetes & Metabolism Journal.2021; 45(5): 698. CrossRef
Increase of BACE1, Brain-Renal Risk Factor, Contributes to Kidney Damage in an Alzheimer’s Disease Mouse Model
Yan Shi, Feng Gao, Xiaoli Yang, Dongwei Liu, Qiuxia Han, Zhangsuo Liu, Hanyu Zhu, Yong Shen
Journal of Alzheimer's Disease.2020; 76(1): 237. CrossRef
Lower Leg Fat Depots Are Associated with Albuminuria Independently of Obesity, Insulin Resistance, and Metabolic Syndrome (Korea National Health and Nutrition Examination Surveys 2008 to 2011)
Eugene Han, Nan Hee Cho, Mi Kyung Kim, Hye Soon Kim
Diabetes & Metabolism Journal.2019; 43(4): 461. CrossRef
Evaluation of creatinine-based and cystatin C-based equations for estimation of glomerular filtration rate in type 1 diabetic patients
Caroline Pereira Domingueti, Rodrigo Bastos Fóscolo, Ana Cristina Simões e Silva, Luci Maria S. Dusse, Janice Sepúlveda Reis, Maria das Graças Carvalho, Ana Paula Fernandes, Karina Braga Gomes
Archives of Endocrinology and Metabolism.2016; 60(2): 108. CrossRef

Response

Response: Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus (Diabetes Metab J 2011;35:159-65): Soon Ae Kim, Woo Ho Shim, Eun Hae Lee, Young Mi Lee, Sun Hee Beom, Eun Sook Kim, Jeong Seon Yoo, Ji Sun Nam, Min Ho Cho, Jong Suk Park, Chul Woo Ahn, Kyung Rae Kim; Diabetes Metab J. 2011;35(3):300-301. Published online June 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.3.300

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Efficacy and Safety of Switching from Sitagliptin to Ipragliflozin in Obese Japanese Patients with Type 2 Diabetes Mellitus: A Single-Arm Multicenter Interventional Study
Kentaro Watanabe, Susumu Yamaguchi, Yoshinori Kosakai, Tetsuya Ioji, Hisamitsu Ishihara
Clinical Drug Investigation.2023; 43(12): 927. CrossRef

Original Articles

Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus: Soon Ae Kim, Woo Ho Shim, Eun Hae Lee, Young Mi Lee, Sun Hee Beom, Eun Sook Kim, Jeong Seon Yoo, Ji Sun Nam, Min Ho Cho, Jong Suk Park, Chul Woo Ahn, Kyung Rae Kim; Diabetes Metab J. 2011;35(2):159-165. Published online April 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.2.159

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Background

Sitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects.

Methods

We obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (ΔHbA1c) and fasting plasma glucose (ΔFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in ΔHbA1c or >20% in ΔFPG levels at 24 weeks.

Results

We classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70±2.40 vs. 26.00±2.26, P≤0.01) and were younger (58.83±11.57 years vs. 62.87±12.09 years, P=0.03) than the non-responder group.

Conclusion

In Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders.

Citations

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A.J. Scheen
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Roger Yazbeck, Simone Jaenisch, Michelle Squire, Catherine A. Abbott, Emma Parkinson-Lawrence, Douglas A. Brooks, Ross N. Butler
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S. Del Prato, S. Patel, S. Crowe, M. von Eynatten
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Xiaoling Cai, Wenjia Yang, Yifei Chen, Xueying Gao, Lingli Zhou, Simin Zhang, Xueyao Han, Linong Ji
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In vivo Corneal Confocal Microscopy and Nerve Growth Factor in Diabetic Microvascular Complications.: Ji Sun Nam, Young Jae Cho, Tae Woong Noh, Chul Sik Kim, Jong Suk Park, Min ho Cho, Hai Jin Kim, Ji Eun Yoon, Han Young Jung, Eun Seok Kang, Yu Mie Rhee, Hyung Keun Lee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2007;31(4):351-361. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.351

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Abstract PDF: BACKGROUND
In vivo corneal confocal microscopy (IVCCM) is being recognized as a non-invasive, early diagnostic tool for diabetic neuropathy, for it provides a clear image of corneal subbasal nerve plexus in detail. Nerve growth factors (NGF) are believed to regulate peripheral and central nervous system, neuronal differentiation, and regeneration of damaged nerves, and their role in diabetic neuropathy is being emphasized these days. Moreover, NGFs and receptors are also expressed in retina and renal mesangial cells, suggesting their possible role in the common pathogenesis of diabetic microvascular complications. We plan to examine corneal structures of diabetic patients and compare IVCCM with conventional tools and analyze their serum and tear NGF levels. METHODS: IVCCM, nerve conduction velocity (NCV), and serum, urine, and tear samplings were done to 42 diabetic patients. From IVCCM, we measured corneal nerve density, branch, and tortuosity, total corneal/epithelial thickness, and the number of endothelial/keratocyte cells, and we checked patients' biochemical profiles and serum and tear NGF levels. RESULTS: Patients with more severe neuropathy had less corneal endothelial cells (3105 +/- 218 vs. 2537 +/- 142 vs. 2350 +/- 73/mm3 vs. 1914 +/- 465/mm3, P = 0.02), higher serum NGF (36 +/- 15 vs. 60 +/- 57.66 vs. 80 +/- 57.63 vs. 109 +/- 60.81 pg/mL, P = 0.39) and tear NGF levels (135.00 +/- 11.94 vs. 304.29 +/- 242.44 vs. 538.50 +/- 251.92 vs. 719.50 +/- 92.63 pg/mL, P = 0.01). There was a positive correlation between neuropathy and corneal nerve tortuosity (r2 = 0.479, P = 0.044) and negative correlation between neuropathy and endothelial cell count (r2 = -0.709, P = 0.002). Interestingly, similar changes were seen in other microvascular complications as well. CONCLUSION: Our results provide a possibility of using novel tools, IVCCM and NGF, as common diagnostic tools for diabetic microvascular complications, but it should be followed by a large population study.

Activation of NF-kappaB and AP-1 in Peripheral Blood Mononuclear Cells Isolated from Patients with Diabetic Nephropathy.: Jisun Nam, Min Ho Cho, Jong Suk Park, Geun Taek Lee, Hai Jin Kim, Eun Seok Kang, Yu Mie Lee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hun Joo Ha, Hyun Chul Lee; Korean Diabetes J. 2007;31(3):261-273. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.261

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Abstract PDF: BACKGROUND
We evaluated the role of oxidative stress in diabetic nephropathy by measuring intracellular reactive oxygen species (ROS) and redox-sensitive transcription factors in isolated peripheral mononuclear cells (PBMC). METHODS: From 66 diabetic patients with or without diabetic nephropathy (Group III and II, respectively) and 49 normal control subjects (Group I), spontaneous and stimulated ROS levels, activities of nuclear factor-kappa B (NF-kappaB), activator protein-1 (AP-1), and specificity protein1 (Sp1) in PBMC, urinary and PBMC TGF-beta1 (transforming growth factor-beta1), and 24-hour urinary albumin excretion (UAE) were measured. RESULTS: Spontaneous ROS was significantly higher in group III and II than group I (60.7 +/- 3.3 vs. 60.0 +/- 3.0 vs. 41.1 +/- 2.4%, respectively), and stimulated ROS were significantly higher in Group III compared to Group II (Increment of H2O2-induced ROS production: 21.8 +/- 2.2 vs. 11.1 +/- 2.0%, respectively; increment of PMA-induced ROS production 23.5 +/- 4.5 vs. 21.6 +/- 2.2%, respectively). The activities of NF-kappaB and AP-1, but not of Sp1, were significantly higher in Group III than in Group II (2.53 vs. 2.0 vs. 1.43-fold, respectively). Both PBMC- and urinary TGF-beta1 levels were higher in Group III than Group II (3.23 +/- 0.39 vs. 1.99 +/- 0.68 ng/mg in PBMCs, 16.88 +/- 6.84 vs. 5.61 +/- 1.57 ng/mL in urine, both respectively), and they were significantly correlated with activities of NF-kappaB and AP-1 and 24-hour UAE. CONCLUSIONS: Increased intracellular ROS generation in PBMCs of diabetic patients is involved in the pathogenesis of diabetic nephropathy through activation of NF-kappaB and AP-1, but not Sp1, and increased expression of TGF-beta1.

Relation between Cerebral Arterial Pulsatility and Insulin Resistance in Type 2 Diabetic Patients.: Jong Suk Park, Chul Sik Kim, Hai Jin Kim, Ji Sun Nam, Tae Woong Noh, Chul Woo Ahn, Kyung Yul Lee, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2006;30(5):347-354. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.347

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Abstract PDF

BACKGROUND
Diabetic patients have a 3-fold risk for cerebrovascular disease compared with nondiabetic controls. The aim of the present study was to investigate the association of insulin resistance with pulsatility index (PI) of cerebral arteries in type 2 diabetic patients. METHODS: We compared a group of 90 patients with stroke free, type 2 diabetes and an age- and sex-matched control group of 45 healthy subjects without diabetes. Diabetic patients were divided into 3 groups according to the ISI (insulin sensitivity index). We evaluated PI of the middle cerebral artery (MCA) by transcranial Doppler ultrasonography (TCD) and insulin resistance determined by short insulin tolerance test. RESULTS: The PI was significantly higher in diabetic patients than that in healthy controls (P < 0.05), and also higher in patients with insulin resistance than that in insulin sensitive diabetic patients (P < 0.05). The PI of the MCA was significantly correlated with age (r= 0.465, P < 0.01), duration of diabetes (r = 0.264, P = 0.025), hypertension (r = 0.285, P = 0.015) and inversely correlated with insulin resistance (r = -0.359, P = 0.030).Multiple regression analysis was performed with PI as a dependent variable and insulin resistance as an independent variable along with known clinical risk factors. Age (beta = 0.393, P < 0.01) and duration of diabetes (beta = 0.274, P = 0.043) exhibited a significant independent contribution to PI. CONCLUSIONS: PI might be useful markers of the detection of diabetic cerebrovascular changes and insulin resistance, measured with short insulin tolerance test, showed correlations with PI, but age and duration of diabetes contributed independently to the variability in the PI.

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Factors Affecting Basilar Artery Pulsatility Index on Transcranial Doppler
Ho Tae Jeong, Dae Sik Kim, Kun Woo Kang, Yun Teak Nam, Ji Eun Oh, Eun Kyung Cho
The Korean Journal of Clinical Laboratory Science.2018; 50(4): 477. CrossRef

Long-term Effect of Pioglitazone Treatment in Patients with Type 2 Diabetes.: Jae Hoon Moon, Hye Jin Kim, Soo Kyung Kim, Wan Sub Shim, Eun Seuk Kang, Yumie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(4):264-276. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.264

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Abstract PDF

BACKGROUND
Type 2 diabetes is characterized by impaired insulin secretion and/or insulin resistance. Thiazolidinediones have been shown to ameliorate insulin resistance. The purpose of the present study was to evaluate the long term serial effect of pioglitazone on anthropometrics and metabolic parameters in Korean type 2 diabetes patients. METHODS: One hundred thirteen type 2 diabetes patients (male, 67; female, 46; mean age, 49.1+/-10.8 years) were evaluated before and after 3 months, 6 months and 12 months of treatment with pioglitazone (Actos(TM), 15 mg/day). Anthropometric parameters and metabolic variables were measured. RESULTS: Body weight and body mass index (BMI) were increased in 3 months after pioglitazone treatment (body weight, 68.8+/-12.2 vs 69.8+/-11.9 kg, P < 0.01) without further increase. In women, body weight and BMI tended to increase more (body weight change after 3 months, 0.6+/-1.7 kg vs 1.6+/-1.7 kg, P < 0.01) and longer (3 months vs 6 months) than in men. Fasting plasma glucose (FPG) and HbA1c were decreased in 3 months after pioglitazone treatment (FPG, 7.97+/-2.29 vs 6.94+/-2.01 mmol/L, P < 0.01; HbA1c, 7.7+/-1.5 vs 7.0+/-1.1%, P < 0.01). Hypoglycemic effect of pioglitazone was prominent in women than in men (FPG change after 12 months, -1.80+/-2.54 vs -0.09+/-1.72 mmol/L, P < 0.001; HbA1c change after 12 months, -0.9+/-1.3 vs -0.4+/-1.1%, P < 0.05). Serum high-density lipoprotein cholesterol was increased after 3 months of pioglitazone treatment (1.16+/-0.24 vs 1.31+/-0.28 mmol/L, P < 0.01) without return until the end of this study. Serum triglycerides level decreased at 3 months (basal vs 3 months, 2.29+/-1.86 vs 1.88+/-1.21 mmol/L, P < 0.01) and 6 months (basal vs 6 months, 2.29+/-1.86 vs 1.97+/-1.40 mmol/L, P < 0.05) of pioglitazone treatment, but returned to basal level at 12 months. Liver enzyme, especially serum alanine transferase level decreased after 3 months of pioglitazone treatment (30.8+/-23.7 vs 24.5+/-18.5 IU/L, P < 0.01) without return until the end of this study. Hypoglycemic effect of pioglitazone was associated with basal BMI, fat contents and serum leptin level. CONCLUSION: Korean type 2 diabetes patients with pioglitazone use showed favorable metabolic effect for glycemic control, lipid metabolism and liverfunction, but pioglitazone induced body weight increase may be limited.

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Therapeutic Effect of Quadruple Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus Who Have Insulin Limitations
Won Sang Yoo, Do Hee Kim, Hee Jin Kim, Hyun Kyung Chung
The Journal of Korean Diabetes.2019; 20(2): 117. CrossRef

Effects of Pioglitazone on Cerebral Hemodynamics in Patients of Type 2 Diabetes.: Jong Suk Park, You Jung Lee, Chul Sik Kim, Hai Jin Kim, Jina Park, Chul Woo Ahn, Kyung Yul Lee, Hyeong Jin Kim, Young Jun Won, Hun Ju Ha, Hae Sun Kwak, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2006;30(2):96-103. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.96

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Abstract PDF: BACKGROUND
Atherosclerosis is one of the major causes of morbidity and mortality in patients with type 2 diabetes and pioglitazone has been reported to have antiatherogenic effect. The aim of this study was to investigate whether pioglitazone affects carotid intima-media thickness (IMT) and pulsatility index (PI) in type 2 diabetic patients. METHODS: A total of 40 type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (pioglitazone 15 mg/day with gliclazide 80~320 mg/day for 12 weeks) (n = 20) and control group (gliclazide 80~320 mg/day for 12 weeks) (n = 20). The changes in lipid profile, insulin resistance, IMT, and PI were monitored to determine that pioglitazone improves cerebrovascular blood flow. RESULTS: The pioglitazone treatment significantly increased HDL-C, reduced triglyceride, insulin resistance and PI. IMT tended to decrease but the change was not significant. This study revealed that treatment with pioglitazone was associated with the improvement of cerebrovascular blood flow. CONCLUSIONS: Pioglitazone appears to be effective for the improvement of cerebrovascular blood flow in type 2 diabetic patients

The long term effects of rosiglitazone on serum lipid concentration and body weight.: Wan Sub Shim, Mi Young Do, Soo Kyung Kim, Hae Jin Kim, Kyu Yeon Hur, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(1):17-24. Published online January 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.1.17

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Abstract PDF: BACKGROUND
Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentration and low density lipoprotein (LDL) particle size, it has adverse effects on the increment of total cholesterol (TC) and LDL cholesterol (LDL-C), and body weight in some studies. Such adverse effects of rosiglitazone on the serum lipid profiles and body weight seem to be attributed to the fact that most studies with rosiglitazone are limited to a short period of follow up. The aim of this study was to evaluate the long term effects of rosiglitazone on the serum lipid levels and body weight. MATERIALS AND METHODS: We prospectively evaluated fasting serum glucose, HbA1c, TC, LDL-C, triglyceride, HDL-C and body weight at baseline and every three months after rosiglitazone usage (4mg/d) in 202 type 2 diabetic patients. RESULTS: TC levels had increased maximally at 3 months and thereafter decreased, but were significantly higher at 18 months than those at baseline. LDL-C levels from the first 3 months to 12 months were significantly higher than those at baseline, but after 15 months, LDL-C concentration was not significantly different from the basal LDL-C concentration. HDL-C levels had increased after first 3 months and the increment of HDL-C concentration were maintained. The increment of HDL-C was more prominent in patients with low basal HDL-C concentration than in patients with high basal HDL-C concentration. Body weight from 3 months to 18 months were higher than that at baseline, but after 3 months, body weight did not increase furthermore significantly. CONCLUSIONS: The adverse effects on lipid concentration and body weight of rosiglitazone may attenuate after long term usage of rosiglitazone.

Clinical Characteristics of Non-obese, Adult-onset Diabetes Requiring Insulin Treatment.: Se Eun Park, Wan Sub Shim, Mi Young Do, Eun Seok Kang, Yumie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(6):557-565. Published online November 1, 2005

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Abstract PDF: BACKGROUND
The aim of this study is to clarify the clinical characteristics of non-obese, adult-onset diabetes requiring insulin treatment and to compare the different characteristics of the three groups categorized according to diabetes classification. METHODS: Total 128 diabetic patients who were non-obese (BMI < 25kg/m2) and had been diagnosed with diabetes after 20 years old, requiring insulin treatment were enrolled in the study. We divided the patients into three groups : 56 patients with type 1, 37 with unclassifiable, and 35 with type 2 diabetes. The type of diabetes was assigned by comparing serum C-peptide concentration and clinical phenotypes. RESULTS: Type 2 and unclassifiable diabetes had no differences in BMI, the interval to use insulin, daily insulin dose, the level of HDL cholesterol and the positive rate for GAD Ab, but type 1 diabetes didn't. However, type 1 diabetes and unclassifiable group was lower prevalence of microvascular complications than type 2 diabetes (retinopathy 38.2, 52.8, 84.8 % ; nephropathy 37.7, 36.7, 74.2 % ; neuropathy 36.7, 36.7, 72.7 %, P<0.05). The prevalence of macrovascular complications was higher in the order of type 1, unclassifiable, and type 2 diabetes (11.1, 29.4, 72.7 %, respectively, all P<0.05). CONCLUSION: The clinical characteristics were similar between unclassifiable and type 2 diabetes, but the prevalence of microvascular complication in unclassifiable group had no significant difference compared with type 1 diabetes. The prevalence of macrovascular complications was significantly higher in the order of type 1, unclassifiable, and type 2 diabetes.

The Association of Family History of Diabetes and Obesity in the Development of Type 2 Diabetes.: Wan Sub Shim, Hae Jin Kim, Soo Kyung Kim, Seung Jin Han, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(6):540-547. Published online November 1, 2005

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Abstract PDF: BACKGROUND
Type 2 diabetes is characterized by defects in both insulin secretion and insulin action. Type 2 diabetes has a strong genetic basis, and obesity is also known as a important risk factor for development of diabetes. The relative effects of obesity and family history of diabetes (FHx) to develop diabetes have not been well characterized. The aim of this study was to analyze the relative role of insulin resistance and insulin secretion in the newly diagnosed type 2 diabetic patients according to the presence of FHx and obesity. METHOD: We evaluated the presence of FHx, fasting and postprandial glucose, C-peptide and insulin in 219 newly diagnosed type 2 diabetic patients without the history of drug therapy from Jan. 2003 to Oct. 2004. RESULT: The mean age of patients was 54.7+/-10.2(yr) and the mean BMI was 25.5+/-3.0 kg/m2. The patients with FHx develop diabetes earlier than them without FHx. BMI, fasting glucose, postprandial glucose, fasting C-peptide and HOMAIR value were not different between groups. But postprandial C-peptide, fasting insulin, postprandial insulin and HOMAbeta-cell value were significantly lower in patient with FHx than in them without FHx. Interestingly, obese (BMI > or = 25kg/m2) patients with FHx developed diabetes earlier than nonobese (BMI <25kg/m2) patients with FHx. CONCLUSION: Obesity plays an important role in the determination of the earlier onset of diabetes in patients with FHx. Intentional prevention of obesity may be an important means to prevent, at least delay, the onset of diabetes in the subjects with FHx.

The Association Between White Blood Cell Count and Metabolic Syndrome in Korean Type 2 Diabetes Mellitus.: Wan Sub Shim, Hae Jin Kim, Soo Kyung Kim, Shin Ae Kang, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(5):460-468. Published online September 1, 2005

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Abstract PDF: BACKGOUND: Type 2 diabetes and metabolic syndrome are associated with an increased risk of cardiovascular disease, and inflammation is also closely associated with cardiovascular disease. The white blood cell count, which is a marker of systemic inflammation, has been found to correlated with the risk of cardiovascular disease. The aim of this study was to evaluate the association between metabolic syndrome and the WBC count in type 2 diabetic patients. METHODS: 606 patients (males 318, females 288, BMI 25.6+/-3.2 kg/m2 and duration of diabetes 4.8+/-5.9year) were enrolled. The WBC and differential counts, anthropometry, blood pressure, fasting glucose, insulin and lipid profiles were measured. RESULTS: According to the quartiles of the WBC count, the number of components of metabolic syndrome and percentage of patients with metabolic syndrome were increased in the highest WBC count quartile. The WBC, neutrophil, lymphocyte, monocyte and eosinophil counts increased with increasing number of components of metabolic syndrome, but not that of the basophil count. The WBC, neutrophil, lymphocyte, monocyte and eosinophil counts were higher in patients with metabolic syndrome than in those without. The WBC count was found to be positively correlated with the waist circumference(gamma=0.090), systolic blood pressure(gamma=0.090), diastolic blood pressure(gamma=0.104), triglyceride(gamma=0.252), insulin(gamma=0.168) and HOMAIR(gamma=0.170), but negatively with high-density lipoprotein cholesterol(gamma= -0.167)(P<0.05, respectively). CONCLUSION: Chronic inflammation, as indicated by a higher than normal WBC count, may increased with the increasing number of components of metabolic syndrome.

Association of Haplotype Combinations of Calpain-10 Gene Polymorphisms and the Metabolic Syndrome in Type 2 Diabetes.: Eun Seok Kang, Hye Joo Kim, Sung Min Myoung, Yumie Rhee, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Moonsuk Nam; Korean Diabetes J. 2005;29(5):451-459. Published online September 1, 2005

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Abstract PDF: OBJECTIVE: Patients with metabolic syndrome are at increased risk of developing cardiovascular disease. The combinations of the haplotype created by the alleles of three single nucleotide polymorphisms (SNPs): SNP-43, SNP-19, and SNP-63 of the Calpain 10 gene (CAPN10), have been reported to be associated with the risk of type 2 diabetes (T2DM) in many populations. The aim of this study was to examine the association of the CAPN10 polymorphisms with metabolic syndrome in Korean patients with T2DM. METHODS: Overall, 382 T2DM patients were enrolled in this study. All the subjects were genotyped according to CAPN10 SNP-43, SNP-19 and SNP-63. The restriction fragment length polymorphism method was used for the three SNPs. The baseline presence of the components of metabolic syndrome was determined. RESULTS: 265 (69.4 %) patients were found to have metabolic syndrome. Patients with the 111/121 haplotype combination showed a higher risk of hypertension than the other haplotype combinations (OR=2.334, P=0.010) and also had a significantly higher risk of having metabolic syndrome (OR=1.927, P=0.042). CONCLUSION: The results of this study suggest a role of the novel 111/121 haplotype combination created by the CAPN10 SNPs -43, -19 and -63 in the susceptibility to metabolic syndrome of T2DM patients.

Clinical Meaning of Postprandial Insulin Secretory Function in Korean Type 2 Diabetes Mellitus.: Wan Sub Shim, Soo Kyung Kim, Hae Jin Kim, Se Eun Park, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(4):367-377. Published online July 1, 2005

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Abstract PDF: BACKGROUND
Impaired pancreatic beta-cell responsiveness is associated with type 2 diabetes mellitus. Postprandial insulin deficiency is closely related with fasting plasma glucose, HbA1c and insulin responses to meals, but most studies examining postprandial beta-cell responsiveness have been limited by the small number of type 2 diabetic patients examined. The aim of this study was to evaluate fasting and postprandial insulin secretions in relation to the duration of diabetes, BMI and glycemic control in a large number of patients with variable disease durations. METHODS: We evaluated the fasting plasma glucose, insulin, C-peptide, HbA1c, BMI, postprandial 2 hour glucose, insulin and C-peptide in 1,170(male 662, female 508, age 54.6+/-1.6 years, duration of diabetes 5.2+/-6.3 years, BMI 25.4+/-3.3kg/m(2)) type 2 diabetic patients. The delta C-peptide, delta insulin, fasting(M0) and postprandial(M1) pancreatic beta-cell responsiveness were also calculated. The subjects were divided into three groups according to their duration of diabetes, BMI, and fasting and postprandial C-peptide levels. After adjusting for age, sex and BMI, the correlation of diabetes and HbA1c were correlated parameters. RESULTS: In the group of patients whose duration of diabetes was longer than 10 years, the BMI, fasting, postprandial and delta C-peptide, and M0 and M1 were significantly lower, but age, fasting and postprandial glucose, as well as HbA1c were significantly higher than those in the other groups. There were no significant differences in the fasting and postprandial glucose and HbA1c according to their fasting C-peptide tertiles. However, in the group of patients with the highest postprandial C-peptide tertile, the fasting and postprandial glucose and HbA1c were significantly lower than those in the other groups. The duration of diabetes, after adjustment of age, sex and BMI, was negatively correlated with the fasting, postprandial and delta C-peptide, M0 and M1, but was positively correlated with the fasting and postprandial 2 hour glucose and HbA1c. The HbA1c after adjustment of age, sex and BMI, was positively correlated with duration of diabetes, and fasting and postprandial glucose, but was negatively correlated with fasting postprandial and delta C-peptide, M0 and M1. CONCLUSION: Although the fasting and postprandial insulin secretions were decreased with duration of diabetes, the decrease in the postprandial insulin secretion was more prominent. The postprandial pancreatic responsiveness may be a more important factor in predicting glycemic control in Korean type 2 diabetic patients than the fasting pancreatic responsiveness.

Relationship of LDL Particle Size to IMT and Insulin Resistance in Non-Diabetic Adult.: Jina Park, Chul Sik Kim, Jong Suk Park, Dol Mi Kim, Min Ho Cho, Jee Hyun Kong, Hai Jin Kim, Jeong Ho Kim, Chul Woo Ahn, Kyung Rae Kim, Bong Soo Cha, Sung Kil Lim, Hyun Chul Lee; Korean Diabetes J. 2005;29(4):333-343. Published online July 1, 2005

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Abstract PDF: BACKGROUND
The aims of this study were to investigate the predictor of the low density lipoprotein(LDL) particle size and the relationship of the LDL particle size to the levels of insulin resistance and the carotid intima-media thickness (IMT) in healthy Koreans. METHODS: The subjects were 47 and 89 clinically healthy males and females, aged between 32 and 70years, without medications that could potentially alter glucose and lipid metabolisms. The mean LDL particle size was determined by polyacrylamide tube gel electrophoresis(Lipoprint(r) LDL, Quantimetrix), the insulin resistance using a short insulin tolerance test kit, and the subclinical atherosclerosis from the carotid intima-media thickness. RESULTS: The LDL particle size was found to be significantly correlated with insulin resistance using a simple Pearson's correlation(r=0.233, P<0.01), but the independent predictors of the LDL particle size, as determined by a multiple stepwise regression analysis, were serum triglyceride(TG), high density lipoprotein(HDL) cholesterol level and age(beta=-0.403, P=< 0.001; beta=0.309, P=0.003; beta=-0.219, P=0.016, respectively). Significant relationships were found between an increasing IMT and the traditional risk factors of atherosclerosis: age, LDL cholesterol, HDL cholesterol, systolic and diastolic blood pressure(r=0.490, P<0.001; r=-0.251, P<0.01; r=0.211, P<0.05; r=0.298, P<0.01; r=0.263, P<0.01, respectively). However, no significant correlation was found between an increasing IMT and the LDL particle size (r=-0.172, P=0.075). CONCLUSION: The best predictors for the LDL particle size were the serum TG level, HDL cholesterol level and age. Insulin resistance was not found to be an independent predictor of the LDL particle size. Small dense LDL was not found to be a predictor of the IMT in healthy Koreans.

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