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Volume 37(5); October 2013
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Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and Dichloroacetate
Dumitru Constantin-Teodosiu
Diabetes Metab J. 2013;37(5):301-314.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.301
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  • 47 Crossref
AbstractAbstract PDFPubReader   

Since the mitochondrial pyruvate dehydrogenase complex (PDC) controls the rate of carbohydrate oxidation, impairment of PDC activity mediated by high-fat intake has been advocated as a causative factor for the skeletal muscle insulin resistance, metabolic syndrome, and the onset of type 2 diabetes (T2D). There are also situations where muscle insulin resistance can occur independently from high-fat dietary intake such as sepsis, inflammation, or drug administration though they all may share the same underlying mechanism, i.e., via activation of forkhead box family of transcription factors, and to a lower extent via peroxisome proliferator-activated receptors. The main feature of T2D is a chronic elevation in blood glucose levels. Chronic systemic hyperglycaemia is toxic and can lead to cellular dysfunction that may become irreversible over time due to deterioration of the pericyte cell's ability to provide vascular stability and control to endothelial proliferation. Therefore, it may not be surprising that T2D's complications are mainly macrovascular and microvascular related, i.e., neuropathy, retinopathy, nephropathy, coronary artery, and peripheral vascular diseases. However, life style intervention such as exercise, which is the most potent physiological activator of muscle PDC, along with pharmacological intervention such as administration of dichloroacetate or L-carnitine can prove to be viable strategies for treating muscle insulin resistance in obesity and T2D as they can potentially restore whole body glucose disposal.

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SIRT1 in Type 2 Diabetes: Mechanisms and Therapeutic Potential
Munehiro Kitada, Daisuke Koya
Diabetes Metab J. 2013;37(5):315-325.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.315
  • 6,530 View
  • 96 Download
  • 178 Crossref
AbstractAbstract PDFPubReader   

The prevalence of type 2 diabetes mellitus (T2DM) has been increasing worldwide. Therefore, a novel therapeutic strategy by which to prevent T2DM is urgently required. Calorie restriction (CR) can retard the aging processes, and delay the onset of numerous age-related diseases including diabetes. Metabolic CR mimetics may be therefore included as novel therapeutic targets for T2DM. Sirtuin 1 (SIRT1), a NAD+-dependent histone deacetylase that is induced by CR, is closely associated with lifespan elongation under CR. SIRT1 regulates glucose/lipid metabolism through its deacetylase activity on many substrates. SIRT1 in pancreatic β-cells positively regulates insulin secretion and protects cells from oxidative stress and inflammation, and has positive roles in the metabolic pathway via the modulation in insulin signaling. SIRT1 also regulates adiponectin secretion, inflammation, glucose production, oxidative stress, mitochondrial function, and circadian rhythms. Several SIRT1 activators, including resveratrol have been demonstrated to have beneficial effects on glucose homeostasis and insulin sensitivity in animal models of insulin resistance. Therefore, SIRT1 may be a novel therapeutic target for the prevention of T2DM, implicating with CR. In this review, we summarize current understanding of the biological functions of SIRT1 and discuss its potential as a promising therapeutic target for T2DM.

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Refocusing Peroxisome Proliferator Activated Receptor-α: A New Insight for Therapeutic Roles in Diabetes
Hannah Seok, Bong Soo Cha
Diabetes Metab J. 2013;37(5):326-332.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.326
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AbstractAbstract PDFPubReader   

Although glucose-lowering treatment shows some risk lowering effects in cardiovascular diseases, risks of macrovascular and microvascular complications have still remained, and development of new therapeutic strategies is needed. Recent data have shown that peroxisome proliferator activated receptor-α (PPAR-α) plays a pivotal role in the regulation of lipid homeostasis, fatty acid oxidation, cellular differentiation, and immune response such as inflammation or vascularization related to diabetic complication. This review will re-examine the metabolic role of PPAR-α, summarize data from clinical studies on the effect of PPAR-α agonist in diabetes, and will discuss the possible therapeutic role of PPAR-α activation.

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The Interplay between Autophagy and Aging
Jong-Ok Pyo, Seung-Min Yoo, Yong-Keun Jung
Diabetes Metab J. 2013;37(5):333-339.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.333
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AbstractAbstract PDFPubReader   

Numerous studies have established a link between autophagy and aging; however, the relationship has not been clearly defined. Aging is a very complex process caused by the accumulation of various factors due to the gradual failure of cellular maintenance. Recent studies have shown that autophagy reduces the stress responses induced by starvation, reactive oxygen species, and the accumulation of intracellular proteins and organelles through cytoprotection, clearance of damaged mitochondria, and lysosomal degradation. Here, we summarize our current understanding of the relationship between autophagy and the aging process.

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Editorial
Diagnosing Diabetes with Hemoglobin A1c: Current Debates and Considerations for Anemic Patients
Tae Hyuk Kim, Sung Hee Choi
Diabetes Metab J. 2013;37(5):340-342.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.340
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PDFPubReader   

Citations

Citations to this article as recorded by  
  • Derivation and validation of an HbA1c optimal cutoff for diagnosing prediabetes in a South African mixed ancestry population
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Original Articles
Hemoglobin A1c May Be an Inadequate Diagnostic Tool for Diabetes Mellitus in Anemic Subjects
Jung Il Son, Sang Youl Rhee, Jeong-taek Woo, Jin Kyung Hwang, Sang Ouk Chin, Suk Chon, Seungjoon Oh, Sung Woon Kim, Young Seol Kim
Diabetes Metab J. 2013;37(5):343-348.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.343
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AbstractAbstract PDFPubReader   
Background

Recently, a hemoglobin A1c (HbA1c) level of 6.5% has been determined to be a criterion for diabetes mellitus (DM), and it is a widely used marker for the diagnosis of DM. However, HbA1c may be influenced by a number of factors. Anemia is one of the most prevalent diseases with an influence on HbA1c; however, its effect on HbA1c varies based on the variable pathophysiology of anemia. The aim of this study was to determine the effect of anemia on HbA1c levels.

Methods

Anemic subjects (n=112) and age- and sex-matched controls (n=217) who were drug naive and suspected of having DM were enrolled. The subjects underwent an oral glucose tolerance test and HbA1c simultaneously. We compared mean HbA1c and its sensitivity and specificity for diagnosing DM between each subgroup.

Results

Clinical characteristics were found to be similar between each subgroup. Also, when glucose levels were within the normal range, the difference in mean HbA1c was not significant (P=0.580). However, when plasma glucose levels were above the diagnostic cutoff for prediabetes and DM, the mean HbA1c of the anemic subgroup was modestly higher than in the nonanemic group. The specificity of HbA1c for diagnosis of DM was significantly lower in the anemic subgroup (P<0.05).

Conclusion

These results suggest that the diagnostic significance of HbA1c might be limited in anemic patients.

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Prevalence of Diabetes and Prediabetes according to Fasting Plasma Glucose and HbA1c
Ja Young Jeon, Seung-Hyun Ko, Hyuk-Sang Kwon, Nan Hee Kim, Jae Hyeon Kim, Chul Sik Kim, Kee-Ho Song, Jong Chul Won, Soo Lim, Sung Hee Choi, Myoung-jin Jang, Yuna Kim, Kyungwon Oh, Dae Jung Kim, Bong-Yun Cha
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DOI: https://doi.org/10.4093/dmj.2013.37.5.349
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AbstractAbstract PDFPubReader   
Background

Due to the inconvenience of performing oral glucose tolerance tests and day to day variability in glucose level, glycated hemoglobin (HbA1c) has been recommended by the American Diabetes Association as a method to diagnose diabetes. In addition, the Korean Diabetes Association has also recommended the use of HbA1c as a diagnostic test for diabetes. In this study, we evaluated the prevalence of diabetes according to fasting plasma glucose (FPG) level only or the combination of FPG and HbA1c tests.

Methods

Data from the 2011 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed. Among 5,811 subjects aged 30 years or older, 5,020 were selected after excluding the data of fasting time <8 hours, missing values from fasting glucose or HbA1c level, previous diagnosis of diabetes made by physicians, or current use of antidiabetic medications. Diabetes was defined as FPG ≥126 mg/dL, previous diagnosis of diabetes made by a medical doctor, current use of antidiabetic medications, and/or HbA1c ≥6.5%. Prediabetes was defined as FPG of 100 to 125 mg/dL and/or HbA1c of 5.7% to 6.4%.

Results

When we used FPG only, the prevalence of diabetes and prediabetes were 10.5% (men, 12.6%; women, 8.5%) and 19.3% (men, 23.8%; women, 14.9%), respectively. When HbA1c was included as a diagnostic test, the prevalence of diabetes and prediabetes increased to 12.4% (men, 14.5%; women, 10.4%) and 38.3% (men, 41%; women, 35.7%), respectively. Participants with HbA1c ≥6.5% and fasting glucose level <126 mg/dL were older and had lower estimated glomerular filtration rate.

Conclusion

We concluded that using fasting glucose level only may result in an underestimation of diabetes and prediabetes. HbA1c is an acceptable complementary diagnostic test for diabetes in Korean patients. However, national standardization is needed to order to use HbA1c as a diagnostic method of diabetes and prediabetes.

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Effect of Treadmill Exercise on Interleukin-15 Expression and Glucose Tolerance in Zucker Diabetic Fatty Rats
Hee-Jae Kim, Jae Young Park, Seung Lyul Oh, Yong-An Kim, Byunghun So, Je Kyung Seong, Wook Song
Diabetes Metab J. 2013;37(5):358-364.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.358
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AbstractAbstract PDFPubReader   
Background

Interleukin-15 (IL-15), a well-known myokine, is highly expressed in skeletal muscle and is involved in muscle-fat crosstalk. Recently, a role of skeletal muscle-derived IL-15 in the improvement of glucose homeostasis and insulin sensitivity has been proposed. However, little is known regarding the influence of endurance training on IL-15 expression in type 2 diabetic skeletal muscles. We investigated the effect of endurance exercise training on glucose tolerance and IL-15 expression in skeletal muscles using type 2 diabetic animal models.

Methods

Male Zucker diabetic fatty (ZDF) and ZDF lean control (ZLC) rats were randomly divided into three groups: sedentary ZLC, sedentary ZDF (ZDF-Con), and exercised ZDF (ZDF-Ex). The ZDF-Ex rats were forced to run a motor-driven treadmill for 60 minutes once a day 5 times per week for 12 weeks. Intraperitoneal glucose tolerance test (IPGTT) was performed after 12 weeks. Expression of IL-15 was measured using ELISA in extracted soleus (SOL) and gastrocnemius medial muscles.

Results

After 12 weeks of treadmill training, reduction of body weight was observed in ZDF-Ex compared to ZDF-Con rats. Glucose tolerance using IPGTT in diabetic rats was significantly improved in ZDF-Ex rats. Furthermore, the expression of IL-15 was significantly increased (P<0.01) only in the SOL of ZDF-Ex rats compared to ZDF-Con. Additionally, IL-15 expression in SOL muscles was negatively correlated with change of body weight (R=-0.424, P=0.04).

Conclusion

The present study results suggest that 12 weeks of progressive endurance training significantly improved glucose tolerance with concomitant increase of IL-15 expression in SOL muscles of type 2 diabetic rats.

Citations

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Risk Factors for the Progression of Intima-Media Thickness of Carotid Arteries: A 2-Year Follow-Up Study in Patients with Newly Diagnosed Type 2 Diabetes
Sang Ouk Chin, Jin Kyung Hwang, Sang Youl Rhee, Suk Chon, You-Cheol Hwang, Seungjoon Oh, Kyu Jeung Ahn, Ho Yeon Chung, Jeong-taek Woo, Sung-Woon Kim, Young Seol Kim, Ja-Heon Kang, In-Kyung Jeong
Diabetes Metab J. 2013;37(5):365-374.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.365
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Intima-media thickness (IMT) of the carotid arteries is known to have a positive correlation with the risk of cardiovascular disease. This study was designed to identify risk factors affecting the progression of carotid IMT in patients with type 2 diabetes mellitus (T2DM).

Methods

Patients with newly diagnosed T2DM with carotid IMT measurements were enrolled, and their clinical data and carotid IMT results at baseline and 2 years later were compared.

Results

Of the 171 patients, 67.2% of males and 50.8% of females had abnormal baseline IMT of the left common carotid artery. At baseline, systolic blood pressure, body mass index and smoking in male participants, and fasting plasma glucose and glycated hemoglobin levels in females were significantly higher in patients with abnormal IMT than in those with normal IMT. Low density lipoprotein cholesterol (LDL-C) levels in males and high density lipoprotein cholesterol (HDL-C) levels in females at the 2-year follow-up were significantly different between the nonprogression and the progression groups. Reduction of the United Kingdom Prospective Diabetes Study (UKPDS) 10-year coronary heart disease (CHD) risk score after 2 years was generally higher in the nonprogression group than the progression group.

Conclusion

LDL-C levels in males and HDL-C levels in females at the 2-year follow-up were significantly different between participants with and without progression of carotid IMT. Furthermore, a reduction in the UKPDS 10-year CHD risk score appeared to delay the advancement of atherosclerosis. Therefore, the importance of establishing the therapeutic goal of lipid profiles should be emphasized to prevent the progression of carotid IMT in newly diagnosed T2DM patients.

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Ruboxistaurin for the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review of Randomized Clinical Trials
Dipika Bansal, Yogesh Badhan, Kapil Gudala, Fabrizio Schifano
Diabetes Metab J. 2013;37(5):375-384.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.375
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AbstractAbstract PDFPubReader   
Background

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus. Protein kinase C (PKC) inhibitor's has been thought to be a potential disease modifying drug's in DPN as it slows or reverse neuropathy's progression. To assesses the efficacy and safety of ruboxistaurin on the progression of symptoms, signs, or functional disability in DPN.

Methods

A systematic review of the literature databases like PubMed, ProQuest, EBSCO, EMBASE, and Cochrane Central was performed up to August 2012. We included randomized controlled trials (RCTs) comparing PKC inhibitor ruboxistaurin (RBX) with control and lasting at least 6 months. Our primary outcome measure was change in neurological examination, measured by neurological total symptom score (NTSS) and vibration detection threshold (VDT). Secondary outcome measures were total quality of life (QoL), skin microvascular blood flow and others.

Results

Six RCTs were included in review. Change in neurological function assessed by NTSS was reported in six studies, out of which significant difference between the RBX and placebo group seen in four studies favouring treatment group while remaining two studies reported no significant difference. VDT was assessed in only one study in which no significant difference seen between RBX and placebo group. Two studies reported significant improvement in QoL data. Safety data was reported in only two studies in which none of side effect was related to RBX.

Conclusion

RBX had effects on DPN in some studies, but the evidence is not enough for meta-analysis and firm conclusion.

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Predicting Mortality of Critically Ill Patients by Blood Glucose Levels
Byung Sam Park, Ji Sung Yoon, Jun Sung Moon, Kyu Chang Won, Hyoung Woo Lee
Diabetes Metab J. 2013;37(5):385-390.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.385
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AbstractAbstract PDFPubReader   
Background

The aim of this study is to observe the outcome of critically ill patients in relation to blood glucose level at admission and to determine the optimal range of blood glucose at admission predicting lower hospital mortality among critically ill patients.

Methods

We conducted a retrospective cohort study of a total 1,224 subjects (males, 798; females, 426) admitted to intensive care unit (ICU) from 1 January 2009 to 31 December 2010. Blood glucose levels at admission were categorized into four groups (group 1, <100 mg/dL; group 2, 100 to 199 mg/dL; group 3, 200 to 299 mg/dL; and group 4, ≥300 mg/dL).

Results

Among 1,224 patients, 319 patients were already known diabetics, and 296 patients died in ICU. Five hundred fifty-seven subjects received insulin therapy, and 118 received oral hypoglycemic agents. The overall mortality rate was 24.2% (296 patients). The causes of death and mortality rates of diabetic patients were not different from nondiabetic subjects. The mortality curve showed J shape, and there were significant differences in mortality between the groups of blood glucose levels at admission. Group 2 had the lowest mortality rate (P<0.05).

Conclusion

These results suggest that serum glucose levels upon admission into ICU is associated with clinical outcomes in ICU patients. Blood glucose level between 100 and 199 mg/dL at the time of ICU admission could predict lower hospital mortality among critically ill patients.

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Letter
Letter: Diabetic Retinopathy and Endothelial Dysfunction in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2013;37:262-9)
Seok Man Son
Diabetes Metab J. 2013;37(5):391-392.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.391
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Response
Response: Diabetic Retinopathy and Endothelial Dysfunction in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2013;37:262-9)
Jae-Seung Yun, Yu-Bae Ahn
Diabetes Metab J. 2013;37(5):393-394.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.393
  • 2,562 View
  • 24 Download
  • 1 Crossref
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    Yudi Purnomo, Djoko W. Soeatmadji, M. Aris Widodo
    Russian Open Medical Journal.2020;[Epub]     CrossRef

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