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Original Article
Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea
Chang-Yun Woo, Ji Yun Jeong, Jung Eun Jang, Jaechan Leem, Chang Hee Jung, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Jung Bok Lee, Ki-Up Lee
Diabetes Metab J. 2015;39(2):126-131.   Published online March 9, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.126
  • 5,503 View
  • 85 Download
  • 23 Web of Science
  • 20 Crossref
AbstractAbstract PDFPubReader   
Background

Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare.

Methods

To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital.

Results

Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis.

Conclusion

The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.

Citations

Citations to this article as recorded by  
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Review
Transcriptional Regulation of Pyruvate Dehydrogenase Kinase
Ji Yun Jeong, Nam Ho Jeoung, Keun-Gyu Park, In-Kyu Lee
Diabetes Metab J. 2012;36(5):328-335.   Published online October 18, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.5.328
  • 5,894 View
  • 125 Download
  • 111 Crossref
AbstractAbstract PDFPubReader   

The pyruvate dehydrogenase complex (PDC) activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK) isoenzymes. Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally regulated still remains unclear. Insulin represses the expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt signaling pathway. Several nuclear hormone receptors activated due to fasting or increased fat supply, including peroxisome proliferator-activated receptors, glucocorticoid receptors, estrogen-related receptors, and thyroid hormone receptors, also participate in the up-regulation of PDK2 and PDK4; however, the endogenous ligands that bind those nuclear receptors have not been identified. It has been recently suggested that growth hormone, adiponectin, epinephrine, and rosiglitazone also control the expression of PDK4 in tissue-specific manners. In this review, we discuss several factors involved in the expressional regulation of PDK2 and PDK4, and introduce current studies aimed at providing a better understanding of the molecular mechanisms that underlie the development of metabolic diseases such as diabetes.

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Original Articles
The Relationship Between Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes.
Hyun Ae Seo, Yeon Kyung Choi, Jae Han Jeon, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, In Kyu Lee, Bo Wan Kim, Jung Guk Kim
Korean Diabetes J. 2009;33(6):485-493.   Published online December 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.6.485
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AbstractAbstract PDF
BACKGROUND
The incidence of type 2 diabetes mellitus is increasing annually and patient mortality is high. Coronary artery calcification is a predictor of coronary artery disease. Cardiovascular events, which are the main cause of death in type 2 diabetes patients, may be preventable by addressing risk factors associated with coronary artery calcification. We examined the relationships between coronary artery calcification, lipid profiles, and apolipoprotein levels. METHODS: We calculated the coronary calcium scores (CCS) of 254 subjects with type 2 diabetes (113 males, 141 females) via multi-detector row computed tomography (MDCT). Height, body weight, blood pressure, HbA1c, c-peptide, lipid profile and apolipoprotein were assessed concurrently. RESULTS: In patients with type 2 diabetes, Agatston score and apolipoprotein A-1 were significantly negatively correlated in both males and females (males P = 0.015, females P = 0.021). The negative correlation between Agatston score and apolipoprotein A-1 was retained for the entire patient sample after adjustments for age and sex (P = 0.022). Stepwise multiple regression anaylses with the Agatston score as the dependent variable indicate that apolipoprotein A-1 is a independent predictor (beta coefficient = -0.047, 95%CI = -0.072 ~ -0.021, P < 0.001) of coronary artery calcification. CONCLUSION: The results of our study suggest that apolipoprotein A-1 is a useful independent indicator of coronary artery calcification.

Citations

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  • The Risk of Coronary Artery Calcification according to Different Lipid Parameters and Average Lipid Parameters
    Tae Kyung Yoo, Mi Yeon Lee, Ki-Chul Sung
    Journal of Atherosclerosis and Thrombosis.2024;[Epub]     CrossRef
  • Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes
    Ki Won Oh
    Korean Diabetes Journal.2009; 33(6): 464.     CrossRef
Leptin is Negatively Associated with Femoral Bone Mineral Density in Postmenopausal Women with Type 2 Diabetes Mellitus.
Jae Han Jeon, Yeun Kyung Choi, Hyun Ae Seo, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, Ju Young Lee, Jung Guk Kim, Bo Wan Kim, In Kyu Lee
Korean Diabetes J. 2009;33(5):421-431.   Published online October 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.5.421
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  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Serum leptin level and bone mineral density (BMD) are widely assumed to be positively associated with body fat mass. Numerous attempts have been made to document the relationship between leptin and BMD, but the results are inconsistent, especially in diabetic patients. METHODS: A total of 60 Korean postmenopausal women with type 2 diabetes mellitus were included in the present study. The BMDs of lumbar spines (L1 to L4) and proximal femurs (trochanter, neck, and total) were measured by dual-energy X-ray absorptiometry (DXA), and biochemical markers including leptin, HbA1c, C-peptide and urine albumin-creatinine ratio (ACR) were measured for each patient. RESULTS: Negative associations between leptin and BMD of femoral neck, trochanter, and total femur in postmenopausal women with type 2 diabetes mellitus were documented in a model adjusted for age, body fat mass, and fasting insulin level (r = -0.308, P = 0.020 and r = - 0.303, P = 0.025 and r = - 0.290, P = 0.032 respectively). Multiple linear regression analysis was performed revealing negative associations between leptin and BMD of the femoral neck (beta = -0.369), trochanter (beta = -0.324), and total femur (beta = -0.317). CONCLUSION: The results of the present study suggest a negative relationship between leptin and femoral BMD. In addition, leptin may have a negative effect on BMD in postmenopausal women with type 2 diabetes mellitus.

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  • Evaluation of bone mineral density in type 2 diabetes mellitus patients before and after treatment
    MK Dutta, R Pakhetra, MK Garg
    Medical Journal Armed Forces India.2012; 68(1): 48.     CrossRef
Maximal Muscle Strength Deteriorates with Age in Subjects with Type 2 Diabetes Mellitus.
Hwi Ryun Kwon, Yun Hyi Ku, Hee Jung Ahn, Ji Yun Jeong, Sang Ryol Ryu, Bo Kyung Koo, Kyung Ah Han, Kyung Wan Min
Korean Diabetes J. 2009;33(5):412-420.   Published online October 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.5.412
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AbstractAbstract PDF
BACKGROUND
It is difficult to improve muscle strength with only aerobic exercise training in type 2 diabetes patients. Resistance training is effective for improving muscle mass, muscle strength and insulin sensitivity. One repetition maxima (1RM), or the maximum amount of weight a subject can lift in a single repetition, may be a useful unit for evaluating the results of resistance training in type 2 diabetic patients. This study was aimed to assess baseline values for 1RM in a sample of Korean type 2 diabetes mellitus patients that are scaled for intensity and load of exercise, and to assess the relationship of 1RM to age. METHODS: A total of 266 (male: 95, female: 171) Korean patients with type 2 diabetes mellitus were included in the study sample. Maximal muscle strength was assessed by measuring 1RM for each subject (KEISER, Fresno, CA, USA). Two different exercises were used to measure 1RM: the chest press for the upper extremities, and the leg press for the lower extremities. RESULTS: Both upper and lower values of 1RM decreased with age in men and women; upper 1RM: r = -0.454, P<0.001 in men, r = -0.480, P< 0.001 in women, lower 1RM: r = -0.569, P<0.001 in men, and r = -0.452, P<0.001 in women. Values of 1RM significantly decreased in men only after the age of 70. In women, values of 1RM continuously decreased after the age of 60. CONCLUSION: The maximal muscle strength of individuals with type 2 diabetes decreases with age. We believe that resistance training is especially beneficial for type 2 diabetes mellitus patients after the sixth decade of life.

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  • The Effects of Floor-seated Exercise Program on Physical Fitness, Depression, and Sleep in Older Adults: A Cluster Randomized Controlled Trial
    Min-Jung Choi, Kyeong-Yae Sohng
    International Journal of Gerontology.2018; 12(2): 116.     CrossRef
  • The Effects of Aerobic/Resistance Exercise on Body Fat Mass, Muscle Strength and Endothelial Function in Korean Type 2 Diabetes mellitus Patients
    Kyung Wan Min
    Journal of Korean Diabetes.2011; 12(1): 6.     CrossRef
  • The Correlations between Extremity Circumferences with Total and Regional Amounts of Skeletal Muscle and Muscle Strength in Obese Women with Type 2 Diabetes
    Hwi Ryun Kwon, Kyung Ah Han, Hee Jung Ahn, Jae Hyuk Lee, Gang Seo Park, Kyung Wan Min
    Diabetes & Metabolism Journal.2011; 35(4): 374.     CrossRef
  • The Effects of Resistance Training on Muscle and Body Fat Mass and Muscle Strength in Type 2 Diabetic Women
    Hwi Ryun Kwon, Kyung Ah Han, Yun Hyi Ku, Hee Jung Ahn, Bo-Kyung Koo, Ho Chul Kim, Kyung Wan Min
    Korean Diabetes Journal.2010; 34(2): 101.     CrossRef
  • Relationship of Maximal Muscle Strength with Body Mass Index and Aerobics Capacity in Type 2 Diabetic Patients
    Hwi Ryun Kwon, Kyung Ah Han, Yun Hyi Ku, Hee Jung Ahn, Bo Kyung Koo, Kyung Wan Min
    Korean Diabetes Journal.2009; 33(6): 511.     CrossRef
Randomized Controlled Trial
Effects of Aerobic Exercise Intensity on Insulin Resistance in Patients with Type 2 Diabetes Mellitus.
Yun Hyi Ku, Bo Kyung Koo, Hee Jung Ahn, Ji Yun Jeong, Hee Geum Seok, Ho Chul Kim, Kyung Ah Han, Kyung Wan Min
Korean Diabetes J. 2009;33(5):401-411.   Published online October 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.5.401
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AbstractAbstract PDF
BACKGROUND
Exercise offers protection against atherosclerosis and insulin resistance. We evaluated the benefits of exercise at different levels of intensity for ameliorating inflammation, endothelial dysfunction, and insulin resistance in a sample of type 2 diabetic subjects. METHODS: Fifty-nine overweight women with type 2 diabetes were randomly assigned to control (CG, N = 18), moderate-intensity exercise (MEG, N = 17), and vigorous-intensity exercise (VEG, N = 14) groups. Patients in the two experimental groups completed a 12-week exercise program, with their exercise activities monitored by accelerometers. We assessed the patients' body weights, total abdominal fat (TF), subcutaneous fat (SF) and visceral fat (VF) via computed tomography, measurements of plasma levels of hs-C-reactive protein (hs-CRP) and interleukin-6 (IL-6), assessment of endothelial function by brachial artery flow-mediated dilation (FMD), and evaluation of insulin sensitivity by insulin tolerance tests, at baseline, at the end of the 12-week interventions, and one year after initiation of the study. RESULTS: At baseline, the average age of all subjects was 54 +/- 7 years, and average body mass index (BMI) was 26.9 +/- 2.5 kg/m2. During the intervention, patients in the MEG and VEG groups expended comparable amounts of activity-related calories (488.6 +/- 111.9 kcal/day, 518.8 +/- 104.1 kcal/day, respectively). Although BMI, TF, and SF decreased similarly in the MEG and VEG groups (deltaBMI: -1.1 +/- 0.7, -0.8 +/- 0.5, deltaTF: -4,647 +/- 3,613 mm2, -2,577 +/- 2,872 mm2, deltaSF: -2,057 +/- 2,021 mm2, -1,141 +/- 1,825 mm2, respectively), compared to control (P<0.01), hs-CRP, IL-6, and FMD remained constant in both exercise groups even after completion of the 12-week exercise intervention. Insulin sensitivity improved only in patients subjected to vigorous exercise (VEG). Visceral fat loss was observed only in patients subjected to moderate exercise (MEG). At one-year follow up, these values had all returned to baseline. CONCLUSION: Exercise vigorous enough to result in significant weight and fat reduction did not ameliorate inflammation and endothelial dysfunction as measured at the end of a 12-week exercise intervention, nor did it result in sustained improvements in insulin sensitivity in type 2 diabetic subjects.

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Original Article
Anti-GAD Antibody in Patients with Adult-Onset Diabetes in Korea.
Sang Ah Lee, Eui Young Kim, Eun Hee Kim, Ji Yun Jeong, Eun Heui Jeong, Dong Woo Kim, Eun Hee Cho, Eun Hee Koh, Min Seon Kim, Joong Yeol Park, Ki Up Lee
Korean Diabetes J. 2009;33(1):16-23.   Published online February 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.1.16
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AbstractAbstract PDF
BACKGROUND
It is well known that the clinical characteristics of diabetes mellitus in Korean people are different from those of Western people. The purpose of this study was to investigate the prevalence of the anti-GAD antibody (GADA) in a large number of Korean patients with adult-onset diabetes. METHODS: The GADA was measured by radioimmunoassay for 11,472 adult-onset diabetic patients who visited the Asan Medical Center from 1998 to 2007. According to the fasting C-peptide levels, we classified the patients into an insulin dependent diabetes mellitus group (IDDM; C-peptide < 0.6 ng/mL) and non-insulin dependent diabetes mellitus group (NIDDM; C-peptide > or = 1.0 ng/mL). Other clinical and laboratory data were obtained from medical records. RESULTS: Among the 11,147 diabetic patients, 9,250 patients were classified as NIDDM, 922 patients were classified as IDDM and 975 patients excluded. Within the latter group 472 patients were to absolute insulin deficient (C-peptide < 0.1 ng/mL). The prevalence of GADA was 22.0% in the IDDM group and 4.7% in the NIDDM group. GADA was more prevalent in younger-onset NIDDM patients (25~40 years of age; 12.4%) than in older-onset NIDDM patients (> or = 40 years of age; 3.8%). The GADA-positive NIDDM patients had lower C-peptide and BMI levels, and higher rates of typical diabetic symptoms and insulin treatment. CONCLUSION: The prevalence of GADA in Korean patients with IDDM and NIDDM was lower than that reported in Western populations. It is thus suggested that autoimmunity is a rarer cause of diabetes in Korean people. However, since over 10% of younger-onset NIDDM patients were positive for GADA, routine GADA measurement in such patients is recommended.

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