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Volume 36(4); August 2012
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The Role of Oxidative Stress in the Pathogenesis of Diabetic Vascular Complications
Shuji Sasaki, Toyoshi Inoguchi
Diabetes Metab J. 2012;36(4):255-261.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.255
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  • 62 Download
  • 60 Crossref
AbstractAbstract PDFPubReader   

Oxidative stress has been paid increasing attention to as an important causative factor for diabetic vascular complications. Among possible various sources, accumulating evidence has indicated that NAD(P)H oxidase may be the most important source for reactive oxygen species production in diabetic vascular tissues. The mechanisms underlying activation and up-regulation of NAD(P)H oxidase has been supposed to be mediated by high glucose-induced protein kinase C (PKC) activation. In this review article, activation of local renin-angiotensin II system induced by chymase activation is also shown to amplify such a PKC-dependent activation of NAD(P)H oxidase. Additionally, human evidence showing the beneficial effect of antioxidants on diabetic vascular complications. Bilirubin has been recognized as a strong endogenous antioxidant. Here markedly lower prevalence of vascular complications is shown in diabetic patients with Gilbert syndrome, a congenital hyperbilirubinemia, as well as reduced markers of oxidative stress and inflammation. Lastly, statin, angiotensin II receptor blocker, chymase inhibitor, bilirubin and biliverdin, PKC β isoform inhibitor, and glucagon-like peptide-1 analog, are shown to serve as antioxidants and have some beneficial effect on diabetic vascular complications, via inhibiting PKC-NAD(P)H oxidase activation, supporting the notion that this mechanism may be an effective therapeutic target for preventing diabetic vascular complications.

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GLP-1 Receptor Agonist and Non-Alcoholic Fatty Liver Disease
Jinmi Lee, Seok-Woo Hong, Eun-Jung Rhee, Won-Young Lee
Diabetes Metab J. 2012;36(4):262-267.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.262
  • 5,406 View
  • 71 Download
  • 58 Crossref
AbstractAbstract PDFPubReader   

Non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is caused by the disruption of hepatic lipid homeostasis. It is associated with insulin resistance as seen in type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1) is an incretin that increases insulin sensitivity and aids glucose metabolism. In recent in vivo and in vitro studies, GLP-1 presents a novel therapeutic approach against NAFLD by increasing fatty acid oxidation, decreasing lipogenesis, and improving hepatic glucose metabolism. In this report, we provide an overview of the role and mechanism of GLP-1 in relieving NAFLD.

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Obstructive Sleep Apnea and Abnormal Glucose Metabolism
Nan Hee Kim
Diabetes Metab J. 2012;36(4):268-272.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.268
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AbstractAbstract PDFPubReader   

Obstructive sleep apnea (OSA) is a chronic disorder that is prevalent, especially in subjects with obesity or diabetes. OSA is related to several metabolic abnormalities, including diabetes, insulin resistance, hypertension, and cardiovascular diseases. Although Koreans are less obese than Caucasians, the prevalence of OSA is comparable in both groups. Thus, the impact of OSA on metabolism may be similar. Many epidemiologic and experimental studies have demonstrated that OSA is associated with glucose intolerance and insulin resistance via intermittent hypoxia, sleep fragmentation, and sleep deprivation. The effect of continuous positive airway pressure treatment on glucose metabolism is still controversial. Randomized controlled trials are needed to evaluate the ability of OSA treatment to reduce the risk of diabetes and insulin resistance in subjects without diabetes and to ameliorate glucose control in patients with diabetes.

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Editorial
Severe Hypoglycemia in Patients with Diabetes
Jae Seung Yun, Seung-Hyun Ko
Diabetes Metab J. 2012;36(4):273-274.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.273
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PDFPubReader   

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Original Articles
Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via Beta Cell ABCA1
Hannah Seok, Ji Young Lee, Eun Mi Park, Se Eun Park, Jae Hyuk Lee, Seungtaek Lim, Byung-Wan Lee, Eun Seok Kang, Hyun Chul Lee, Bong Soo Cha
Diabetes Metab J. 2012;36(4):275-279.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.275
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AbstractAbstract PDFPubReader   
Background

The aim of this study was to investigate the effects of balsamic vinegar on β-cell dysfunction.

Methods

In this study, 28-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed a normal chow diet or a high-fat diet (HFD) and were provided with tap water or dilute balsamic vinegar for 4 weeks. Oral glucose tolerance tests and histopathological analyses were performed thereafter.

Results

In rats fed both the both chow diet and the HFD, the rats given balsamic vinegar showed increased insulin staining in islets compared with tap water administered rats. Balsamic vinegar administration also increased β-cell ATP-binding cassette transporter subfamily A member 1 (ABCA1) expression in islets and decreased cholesterol levels.

Conclusion

These findings provide the first evidence for an anti-diabetic effect of balsamic vinegar through improvement of β-cell function via increasing β-cell ABCA1 expression.

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Severe Hypoglycemia Is a Serious Complication and Becoming an Economic Burden in Diabetes
Won Chul Ha, Su Jin Oh, Ji Hyun Kim, Jung Min Lee, Sang Ah Chang, Tae Seo Sohn, Hyun Shik Son
Diabetes Metab J. 2012;36(4):280-284.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.280
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AbstractAbstract PDFPubReader   
Background

The prevalence of hypoglycemia is increasing due to the growing incidence of diabetes and the latest strict guidelines for glycated hemoglobin (HbA1c) levels under 7%. This study examined the clinical characteristics, causal factors, and medical costs of severely hypoglycemic patients in an emergency room (ER) of Uijeongbu St. Mary's Hospital.

Methods

The study consisted of a retrospective analysis of the characteristics, risk factors, and medical costs of 320 severely hypoglycemic patients with diabetes who presented to an ER of Uijeongbu St. Mary's Hospital from January 1, 2006 to December 31, 2009.

Results

Most hypoglycemic patients (87.5%, 280/320) were over 60 years old with a mean age of 69.5±10.9 years and a mean HbA1c level of 6.95±1.46%. Mean serum glucose as noted in the ER was 37.9±34.5 mg/dL. Renal function was decreased, serum creatinine was 2.0±2.1 mg/dL and estimated glomerular filtration rate (eGFR) was 48.0±33.6 mL/min/1.73 m2. In addition, hypoglycemic patients typically were taking sulfonylureas or insulin and a variety of other medications, and had a long history of diabetes.

Conclusion

Severe hypoglycemia is frequent in older diabetic patients, subjects with low HbA1c levels, and nephropathic patients. Therefore, personalized attention is warranted, especially in long-term diabetics with multiple comorbidities who may not have been properly educated or may need re-education for hypoglycemia.

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Influence of Visceral Adiposity on Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus
Eun-Hee Jang, Na-Young Kim, Yong-Moon Park, Mee-Kyoung Kim, Ki Hyun Baek, Ki-Ho Song, Kwang Woo Lee, Hyuk-Sang Kwon
Diabetes Metab J. 2012;36(4):285-292.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.285
  • 3,669 View
  • 36 Download
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AbstractAbstract PDFPubReader   
Background

The aim of this study was to investigate the influences of visceral adiposity on cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus.

Methods

Two hundred eleven patients with type 2 diabetes participated in this study. Anthropometric and metabolic parameters were measured, and the visceral fat area was assessed using computed tomography. CAN was diagnosed using a cardiovascular reflex test. We analyzed the correlation between the visceral fat area and each parameter in this test.

Results

The mean age, body mass index (BMI), and duration of diabetes of the study population were 60±14 years (mean±standard deviation), 25.1±4.2 kg/m2, and 12.3±8.9 years, respectively. The visceral fat area showed positive correlations with age, BMI, waist circumference, and subcutaneous fat area. There was no statistically significant difference in the cardiovascular reflex test outcome between genders. Univariate linear regression analysis showed that an increased visceral fat area diminished good heart rate response to a Valsalva maneuver (R2=4.9%, P=0.013 in an unadjusted model), but only in women. This statistical association was preserved after adjusting for age and BMI (R2=9.8%, P=0.0072).

Conclusion

The results of this study suggest that visceral adiposity contributes to an autonomic imbalance to some degree, as demonstrated by the impaired cardiovascular reflex test among women with type 2 diabetes.

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Intracerebroventricular Injection of Metformin Induces Anorexia in Rats
Chang Koo Lee, Yoon Jung Choi, So Young Park, Jong Yeon Kim, Kyu Chang Won, Yong Woon Kim
Diabetes Metab J. 2012;36(4):293-299.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.293
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  • 42 Download
  • 27 Crossref
AbstractAbstract PDFPubReader   
Background

Metformin, an oral biguanide insulin-sensitizing agent, is well known to decrease appetite. Although there is evidence that metformin could affect the brain directly, the exact mechanism is not yet known.

Methods

To evaluate whether metformin induces anorexia via the hypothalamus, various concentrations of metformin were injected into the lateral ventricle of rats through a chronically implanted catheter and food intake was measured for 24 hours. The hypothalamic neuropeptides associated with regulation of food intake were also analyzed following 1 hour of intracerebroventricular (ICV) injections of metformin.

Results

An ICV injection of metformin decreased food intake in a dose-dependent manner in unrestrained conscious rats. Hypothalamic phosphorylated AMP-activated protein kinase (pAMPK) increased by 3 µg with metformin treatment, but there was no further increase in pAMPK with increases in metformin dosage. The hypothalamic phosphorylated signal transducer and activator of transcription 3 (pSTAT3) increased by 3 µg with metformin treatment, but, there was no further increase in pSTAT3 level following increases of metformin dosage. Hypothalamic proopiomelanocortin was elevated with metformin treatment, while neuropeptide Y was not significantly changed.

Conclusion

Our results suggest that metformin induces anorexia via direct action in the hypothalamus and the increase in pSTAT3, at least in part, is involved in the process. However, hypothalamic pAMPK appears not to contribute to metformin-induced appetite reduction in normal rats. Further studies exploring new pathways connecting metformin and feeding regulation are needed.

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Total Energy Intake May Be More Associated with Glycemic Control Compared to Each Proportion of Macronutrients in the Korean Diabetic Population
Hye Mi Kang, Dong-Jun Kim
Diabetes Metab J. 2012;36(4):300-306.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.300
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AbstractAbstract PDFPubReader   
Background

Major macronutrients for energy intake vary among countries and cultures. Carbohydrates, including rice, are the major component of daily energy intake in Korea. The aim of this study was to examine the association of daily energy intake or each proportion of macronutrients, especially carbohydrates, with glycemic control in diabetic Koreans.

Methods

A total of 334 individuals with diabetes (175 men, age 57.4±0.8 years; 159 women, age 60.9±0.9 years) who participated in the 2005 Korean National Health and Nutrition Examination Survey were examined. Glycemic control was categorized based on concentration of glycated hemoglobin (HbA1c; HbA1c ≤6.5%; 6.6% to 8.0%; ≥8.1%). Dietary intake was assessed by using a 24-recall item questionnaire.

Results

High total energy intake was associated with poor glycemic control (HbA1c ≤6.5%, 1,824±75 kcal; 6.6% to 8.0%, 1,990±57 kcal; ≥8.1%, 2,144±73 kcal; P value for trend=0.002). Each proportion of protein, fat, or carbohydrate was not associated with glycemic control. Even after adjusting for several parameters, the association of daily energy intake with glycemic control still persisted.

Conclusion

Total energy intake may be more closely related to glycemic control than each proportionof macronutrients in Korean diabetics.

Citations

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Urinary Neutrophil Gelatinase-Associated Lipocalin Levels in Comparison with Glomerular Filtration Rate for Evaluation of Renal Function in Patients with Diabetic Chronic Kidney Disease
Kwang-Sook Woo, Jae-Lim Choi, Bo-Ram Kim, Ji-Eun Kim, Won-Suk An, Jin-Yeong Han
Diabetes Metab J. 2012;36(4):307-313.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.307
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AbstractAbstract PDFPubReader   
Background

Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury. There is a growing body of evidence suggesting that NGAL is also a marker of kidney disease and severity in chronic kidney disease (CKD). We studied the utility of urinary NGAL in more accurately predicting renal function in patients with diabetic CKD.

Methods

We studied possible relationships between urinary NGAL, estimated glomerular filtration rate (eGFR), and proteinuria in diabetic CKD patients and in healthy populations.

Results

Urinary NGAL levels were significantly higher in CKD patients than in healthy controls (96.0 [2.7 to 975.2] ng/mL vs. 18.8 [1.3 to 81.9] ng/mL, P=0.02), and the GFR was lower among CKD patients (49.3 [13.1 to 78.3] mL/min/1.73 m2 vs. 85.6 [72 to 106.7] mL/min/1.73 m2, P<0.0001). The urinary NGAL level showed a significant inverse correlation with GFR (r=-0.5634, P<0.0001). The correlation analyses between urinary protein level and urinary NGAL levels and GFR were as follows: urine protein and urinary NGAL (r=0.3009, P=0.0256), urine protein and GFR (r=-0.6245, P<0.0001), urine microalbumin and urinary NGAL (r=0.1794, P=0.2275), and urine microalbumin and GFR (r=-0.5190, P=0.0002).

Conclusion

From these results, we concluded that urinary NGAL is a reliable marker of renal function in diabetic CKD patients. However, urinary NGAL did not provide more accurate information regarding renal function than GFR.

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Letter
Letter: Prevalence and Correlates of Disordered Sleep in Southeast Asian Indians with Type 2 Diabetes (Diabetes Metab J 2012;36:70-6)
Tomoyuki Kawada
Diabetes Metab J. 2012;36(4):314-315.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.314
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Response
Response: Prevalence and Correlates of Disordered Sleep in Southeast Asian Indians with Type 2 Diabetes (Diabetes Metab J 2012;36:70-6)
Amarabalan Rajendran, Krishna G. Seshadri
Diabetes Metab J. 2012;36(4):316-316.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.316
  • 2,229 View
  • 28 Download
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Diabetes Metab J : Diabetes & Metabolism Journal