Diabetes & Metabolism Journal

Volume 34(4); August 2010

Review

O-GlcNAc Modification: Friend or Foe in Diabetic Cardiovascular Disease: Udayakumar Karunakaran, Nam Ho Jeoung; Korean Diabetes J. 2010;34(4):211-219. Published online August 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.4.211

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O-Linked β-N-acetyl glucosaminylation (O-GlcNAcylation) is a dynamic post-translational modification that occurs on serine and threonine residues of cytosolic and nuclear proteins in all cell types, including those involved in the cardiovascular system. O-GlcNAcylation is thought to act in a manner analogous to protein phosphorylation. O-GlcNAcylation rapidly cycles on/off proteins in a time scale similar to that for phosphorylation/dephosphorylation of proteins. Several studies indicate that O-GlcNAc might induce nuclear localization of some transcription factors and may affect their DNA binding activities. However, at the cellular level, it has been shown that O-GlcNAc levels increase in response to stress and augmentation of this response suppresses cell survival. Increased levels of O-GlcNAc have been implicated as a pathogenic contributor to glucose toxicity and insulin resistance, which are major hallmarks of type 2 diabetes and diabetes-related cardiovascular complications. Thus, O-GlcNAc and its metabolic functions are not yet well-understood; focusing on the role of O-GlcNAc in the cardiovascular system is a viable target for biomedical investigation. In this review, we summarize our current understanding of the role of O-GlcNAc on the regulation of cell function and survival in the cardiovascular system.

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Editorial

The Adiponectin/Leptin Ratio and Metabolic Syndrome in Healthy Korean Adult Males: Seung-Hyun Ko; Korean Diabetes J. 2010;34(4):220-221. Published online August 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.4.220

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Original Articles

Clinical Characteristics of Type 2 Diabetes Patients according to Family History of Diabetes: Seung Uk Jeong, Dong Gu Kang, Dae Ho Lee, Kang Woo Lee, Dong-Mee Lim, Byung Joon Kim, Keun-Yong Park, Hyoun-Jung Chin, Gwanpyo Koh; Korean Diabetes J. 2010;34(4):222-228. Published online August 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.4.222

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Abstract PDF PubReader

Background

Type 2 diabetes mellitus (T2DM) has a strong genetic component, and its prevalence is notably increased in the family members of T2DM patients. However, there are few studies about the family history of T2DM. We carried out this study to assess the influences of family history on clinical characteristics in T2DM patients.

Methods

This is a cross-sectional study involving 651 T2DM patients. Patient history and physical examination were performed and fasting blood was taken. If any first degree relative was diabetic, a family history of diabetes was considered to exist.

Results

Among the total 621 patients, 38.4% had a family history of diabetes. Patients with a family history had a younger age, higher weight, younger age at diagnosis and higher triglyceride level than did those without a family history. Dyslipidemia medication and metabolic syndrome were more prevalent in familial diabetes. Sex, blood pressure, previous treatment for diabetes, HbA1c, C-peptide, total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol were not different between familial and non-familial diabetes. Upon multiple linear regression analysis, the family history of diabetes remained significantly associated with serum triglyceride level.

Conclusion

In T2DM patients with a family history of diabetes, the disease tended to develop earlier. Metabolic syndrome and cardiovascular risk factors are more prevalent in familial T2DM than they were in non-familial T2DM. These results support the necessity of earlier screening for diabetes in family members of T2DM patients and more active prevention against cardiovascular disease in T2DM patients with a family history.

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Polymorphisms of the Reg1α Gene and Early Onset Type 2 Diabetes in the Korean Population: Bo Kyung Koo, Young Min Cho, Kuchan Kimm, Jong-Young Lee, Bermseok Oh, Byung Lae Park, Hyun Sub Cheong, Hyoung Doo Shin, Kyung Soo Ko, Sang Gyu Park, Hong Kyu Lee, Kyong Soo Park; Korean Diabetes J. 2010;34(4):229-236. Published online August 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.4.229

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Abstract PDF PubReader

Background

The Reg gene has been reported to be expressed in regenerating islets and Reg1 protein to be up-regulated at an early stage of diabetes in mice. As human Reg1α is homologous with murine Reg1, we investigated whether common variants in Reg1α are associated with type 2 diabetes in the Korean population.

Methods

We sequenced the Reg1α gene to identify common polymorphisms using 24 Korean DNA samples. Of 11 polymorphisms found, five common ones (g.-385T>C [rs10165462], g.-36T>G [rs25689789], g.209G>T [rs2070707], g.1385C>G [novel], and g.2199G>A [novel]) were genotyped in 752 type 2 diabetic patients and 642 non-diabetic subjects.

Results

No polymorphism was associated with the risk of type 2 diabetes. However, g.-385C and g.2199A lowered the risk of early-onset type 2 diabetes, defined as a diagnosis in subjects whose age at diagnosis was 25 years or more but less than 40 years (odds ratio [OR], 0.721 [0.535 to 0.971] and 0.731 [0.546 to 0.977] for g.-385C and g.2199A, respectively) and g.1385G increased the risk of early-onset diabetes (OR, 1.398 [1.055 to 1.854]). Although adjusting for errors in multiple hypotheses-testing showed no statistically significant association between the three individual polymorphisms and early-onset diabetes, the haplotype H1, composed of g.-385C, g.1385C, and g.2199A, was associated with a reduced risk of early-onset diabetes (OR, 0.590 [0.396 to 0.877], P = 0.009).

Conclusion

Polymorphisms in the Reg1α were not found to be associated with overall susceptibility to type 2 diabetes, though some showed modest associations with early-onset type 2 diabetes in the Korean population.

Citations

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Glycemic Effects of Once-a-Day Rapid-Acting Insulin Analogue Addition on a Basal Insulin Analogue in Korean Subjects with Poorly Controlled Type 2 Diabetes Mellitus
Eun Yeong Choe, Yong-ho Lee, Byung-Wan Lee, Eun-Seok Kang, Bong Soo Cha, Hyun Chul Lee
Diabetes & Metabolism Journal.2012; 36(3): 230. CrossRef

The Relationship of Adiponectin/Leptin Ratio with Homeostasis Model Assessment Insulin Resistance Index and Metabolic Syndrome in Apparently Healthy Korean Male Adults: Chan-Hee Jung, Eun-Jung Rhee, Ji-Hoon Choi, Ji-Cheol Bae, Seung-Hyun Yoo, Won-Jun Kim, Cheol-Young Park, Ji Oh Mok, Chul Hee Kim, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Sun-Woo Kim; Korean Diabetes J. 2010;34(4):237-243. Published online August 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.4.237

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Background

We investigated the relationships of adiponectin/leptin (A/L) ratio with cardiovascular risk factors, insulin resistance index, and metabolic syndrome (MS) in apparently healthy Korean male adults.

Methods

Sixty-eight male subjects were enrolled among the participants of an annual health check-up program (mean age, 55.1 years). Percent body fat (%) was measured using a bioelectric impedance analyzer. Serum leptin level was measured via radioimmunoassay, and adiponectin level was measured using an enzyme-linked immunosorbent assay. Homeostasis model assessment (HOMA)-insulin resistance (IR) index was calculated, and the presence of metabolic syndrome was assessed.

Results

Adiponectin, leptin, and A/L ratio showed significant correlations with percent body fat, lipid profile, and HOMA-IR. Mean leptin and HOMA-IR levels were significantly higher, while A/L ratio was significantly lower in subjects with MS. With increasing number of MS components, the mean values of leptin and HOMA-IR increased and the A/L ratio decreased. In multiple regression analysis, HOMA-IR was significantly correlated with triglyceride, fasting glucose, and A/L ratio, while A/L ratio was significantly correlated with body mass index and HOMA-IR. HOMA-IR and A/L ratio were significant predictors for each other after adjustment for other factors.

Conclusion

A/L ratio correlated well with lipid profile, HOMA-IR, and the presence and number of MS components in Korean male subjects.

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Effects of Endurance Exercise and High-Fat Diet on Insulin Resistance and Ceramide Contents of Skeletal Muscle in Sprague-Dawley Rats: Hyun Lyung Jung, Ho Youl Kang; Korean Diabetes J. 2010;34(4):244-252. Published online August 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.4.244

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Abstract PDF PubReader

Background

We evaluated the effects of endurance exercise and a high-fat diet on insulin resistance and ceramide contents of skeletal muscle in Sprague-Dawley rats.

Methods

We randomly divided 32 rats into four groups: control (CON, n = 8), high fat diet (HF, n = 8), exercise (Ex, 24 m/min for 2 hours, 5 days/wk, n = 8), HF/Ex (n = 8). After 4-week treatments, plasma lipid profiles, glucose and insulin concentrations were measured. The triglycerides (TG), ceramide, and glucose transporter 4 (GLUT-4) contents were measured in the skeletal muscle. The rate of glucose transport was determined under submaximal insulin concentration during the muscle incubation.

Results

Free fatty acid levels were significantly higher in CON and HF than Ex (P = 0.032). Plasma glucose levels in HF were significantly higher than the two Ex groups (P = 0.002), and insulin levels were significantly higher in HF than in other three groups (P = 0.021). Muscular TG concentrations were significantly higher in HF than CON and Ex and also in HF/Ex than Ex, respectively (P = 0.005). Hepatic TG concentrations were significantly higher in HF than other three groups but Ex was significantly lower than HF/Ex (P = 0.000). Muscular ceramide content in HF was significantly greater than that in either Ex or HF/Ex (P = 0.031). GLUT-4 levels in CON and HF were significantly lower than those in Ex and HF/Ex (P = 0.009, P = 0.003). The glucose transport rate in submaximal insulin concentration was lower in CON than in either Ex or HF/Ex (P = 0.043), but not different from HF.

Conclusion

This study suggests that high fat diet for 4 weeks selectively impairs insulin resistance, but not glucose transport rate, GLUT-4 and ceramide content in skeletal muscle per se. However, endurance exercise markedly affects the content of ceramide and insulin resistance in muscle.

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The Relationship between Lung Function and Metabolic Syndrome in Obese and Non-Obese Korean Adult Males: Soo Kyoung Kim, Kyu Yeon Hur, Yoon Ho Choi, Sun Wook Kim, Jae Hoon Chung, Hee Kyung Kim, Moon-Kyu Lee, Yong-Ki Min, Kwang-Won Kim, Jae Hyeon Kim; Korean Diabetes J. 2010;34(4):253-260. Published online August 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.4.253

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Abstract PDF PubReader

Background

The existence of an association between lung function and metabolic syndrome (MetS) has been debated in cases involving non-obese subjects. To address this debate, we performed a cross-sectional study to investigate the association between lung function and MetS in both obese and non-obese populations.

Methods

The present study consisted of a total of 1,951 Korean male subjects. In this study group, we investigated relationships between lung function and MetS risk factors such as fasting serum glucose, systolic blood pressure (SBP), insulin resistance index, waist circumference (WC), and hemoglobin A_1C level.

Results

Forced vital capacity (FVC) values were significantly lower in the MetS group compared with those of the non-MetS group. In both non-obese (body mass index [BMI] < 25 kg/m²) and obese subjects (BMI ≥ 25 kg/m²), fasting serum glucose, hemoglobin A_1C level, insulin resistance index, SBP, WC, and the prevalences of diabetes and MetS were significantly higher in subjects in the lowest FVC quartile compared with those in the highest FVC quartile. Odds ratios for the presence of MetS risk factors, after adjusting for age and height, ranged from 1.21 to 1.39 (P < 0.01) for a one standard deviation decrease in FVC.

Conclusion

The results of our study suggest that decreased vital capacity in Korean adult male subjects is associated with MetS, irrespective of obesity.

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