Showing papers in "Diabetes & Metabolism Journal in 2013"

AMPK and Exercise: Glucose Uptake and Insulin Sensitivity.

Abstract: AMPK is an evolutionary conserved sensor of cellular energy status that is activated during exercise. Pharmacological activation of AMPK promotes glucose uptake, fatty acid oxidation, mitochondrial biogenesis, and insulin sensitivity; processes that are reduced in obesity and contribute to the development of insulin resistance. AMPK deficient mouse models have been used to provide direct genetic evidence either supporting or refuting a role for AMPK in regulating these processes. Exercise promotes glucose uptake by an insulin dependent mechanism involving AMPK. Exercise is important for improving insulin sensitivity; however, it is not known if AMPK is required for these improvements. Understanding how these metabolic processes are regulated is important for the development of new strategies that target obesity-induced insulin resistance. This review will discuss the involvement of AMPK in regulating skeletal muscle metabolism (glucose uptake, glycogen synthesis, and insulin sensitivity).

SIRT1 in Type 2 Diabetes: Mechanisms and Therapeutic Potential

Abstract: 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.

A systematic review of oxidative stress and safety of antioxidants in diabetes: focus on islets and their defense.

Abstract: A growing body of evidence suggests that hyperglycemia-induced oxidative stress plays an important role in diabetic complications, especially β-cell dysfunction and failure. Under physiological conditions, reactive oxygen species serve as second messengers that facilitate signal transduction and gene expression in pancreatic β-cells. However, under pathological conditions, an imbalance in redox homeostasis leads to aberrant tissue damage and β-cell death due to a lack of antioxidant defense systems. Taking into account the vulnerability of islets to oxidative damage, induction of endogenous antioxidant enzymes or exogenous antioxidant administration has been proposed as a way to protect β-cells against diabetic insults. Here, we consider recent insights into how the redox response becomes deregulated under diabetic conditions, as well as the therapeutic benefits of antioxidants, which may provide clues for developing strategies aimed at the treatment or prevention of diabetes associated with β-cell failure.

Resistin in Rodents and Humans

Abstract: Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resistance. However, in contrast to rodents, resistin is expressed and secreted from macrophages in humans and is increased in inflammatory conditions. Some studies have also suggested an association between increased resistin levels and insulin resistance, diabetes and cardiovascular disease. Genetic studies have provided additional evidence for a role of resistin in insulin resistance and inflammation. Resistin appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and formation of foam cells. Indeed, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. There is also growing evidence that elevated resistin is associated with the development of heart failure. This review will focus on the biology of resistin in rodents and humans, and evidence linking resistin with type 2 diabetes, atherosclerosis, and cardiovascular disease.

Effects of high performance inulin supplementation on glycemic control and antioxidant status in women with type 2 diabetes.

Abstract: Background The purpose of this study was to evaluate the effects of high performance inulin supplementation on blood glycemic control and antioxidant status in women with type 2 diabetes.

Brown Adipose Tissue as a Regulator of Energy Expenditure and Body Fat in Humans

Abstract: Brown adipose tissue (BAT) is recognized as the major site of sympathetically activated nonshivering thermogenesis during cold exposure and after spontaneous hyperphagia, thereby controling whole-body energy expenditure and body fat. In adult humans, BAT has long been believed to be absent or negligible, but recent studies using fluorodeoxyglucose-positron emission tomography, in combination with computed tomography, demonstrated the existence of metabolically active BAT in healthy adult humans. Human BAT is activated by acute cold exposure, being positively correlated to cold-induced increases in energy expenditure. The metabolic activity of BAT differs among individuals, being lower in older and obese individuals. Thus, BAT is recognized as a regulator of whole-body energy expenditure and body fat in humans as in small rodents, and a hopeful target combating obesity and related disorders. In fact, there are some food ingredients such as capsaicin and capsinoids, which have potential to activate and recruit BAT via activity on the specific receptor, transient receptor potential channels, thereby increasing energy expenditure and decreasing body fat modestly and consistently.

Prevalence of Diabetes and Prediabetes according to Fasting Plasma Glucose and HbA1c

Abstract: 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.

Chemokine Systems Link Obesity to Insulin Resistance

Abstract: Obesity is a state of chronic low-grade systemic inflammation This chronic inflammation is deeply involved in insulin resistance, which is the underlying condition of type 2 diabetes and metabolic syndrome A significant advance in our understanding of obesity-associated inflammation and insulin resistance has been recognition of the critical role of adipose tissue macrophages (ATMs) Chemokines are small proteins that direct the trafficking of immune cells to sites of inflammation In addition, chemokines activate the production and secretion of inflammatory cytokines through specific G protein-coupled receptors ATM accumulation through C-C motif chemokine receptor 2 and its ligand monocyte chemoattractant protein-1 is considered pivotal in the development of insulin resistance However, chemokine systems appear to exhibit a high degree of functional redundancy Currently, more than 50 chemokines and 18 chemokine receptors exhibiting various physiological and pathological properties have been discovered Therefore, additional, unidentified chemokine/chemokine receptor pathways that may play significant roles in ATM recruitment and insulin sensitivity remain to be fully identified This review focuses on some of the latest findings on chemokine systems linking obesity to inflammation and subsequent development of insulin resistance

Increased Selenoprotein P Levels in Subjects with Visceral Obesity and Nonalcoholic Fatty Liver Disease

Abstract: BACKGROUND Selenoprotein P (SeP) has recently been reported as a novel hepatokine that regulates insulin resistance and systemic energy metabolism in rodents and humans. We explored the associations among SeP, visceral obesity, and nonalcoholic fatty liver disease (NAFLD). METHODS We examined serum SeP concentrations in subjects with increased visceral fat area (VFA) or liver fat accumulation measured with computed tomography. Our study subjects included 120 nondiabetic individuals selected from participants of the Korean Sarcopenic Obesity Study. In addition, we evaluated the relationship between SeP and cardiometabolic risk factors, including homeostasis model of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hsCRP), adiponectin values, and brachial-ankle pulse wave velocity (baPWV). RESULTS Subjects with NAFLD showed increased levels of HOMA-IR, hsCRP, VFA, and several components of metabolic syndrome and decreased levels of adiponectin and high density lipoprotein cholesterol than those of controls. Serum SeP levels were positively correlated with VFA, hsCRP, and baPWV and negatively correlated with the liver attenuation index. Not only subjects with visceral obesity but also those with NAFLD exhibited significantly increased SeP levels (P<0.001). In multiple logistic regression analysis, the subjects in the highest SeP tertile showed a higher risk for NAFLD than those in the lowest SeP tertile, even after adjusting for potential confounding factors (odds ratio, 7.48; 95% confidence interval, 1.72 to 32.60; P=0.007). CONCLUSION Circulating SeP levels were increased in subjects with NAFLD as well as in those with visceral obesity and may be a novel biomarker for NAFLD.

Relative Skeletal Muscle Mass Is Associated with Development of Metabolic Syndrome

Abstract: Results: Among 838 subjects, 88 (10.5%) were newly diagnosed with MS. Development of MS increased according to increasing quintiles of BMI, SMM, VFA, and SMI, but was negatively associated with SMM%, MFR, and SVR. VFA was positively associated with high waist circumference (WC), high blood pressure (BP), dysglycemia, and high triglyceride (TG). In contrast, MFR was negatively associated with high WC, high BP, dysglycemia, and high TG. SVR was negatively associated with all components of MS. Conclusion: Relative SMM ratio to body composition, rather than absolute mass, may play a critical role in development of MS and could be used as a strong predictor.

Prevalence and Management of Dyslipidemia in Korea: Korea National Health and Nutrition Examination Survey during 1998 to 2010

Abstract: BACKGROUND Dyslipidemia is a major risk factor of cardiovascular disease. The aim of this study was to investigate the changing trends in the prevalence and management status of dyslipidemia among Korean adults. METHODS The prevalence of dyslipidemia and the rates of awareness, treatment, and control of dyslipidemia were investigated in adults aged ≥20 years from the Korea National Health and Nutrition Surveys (KNHANES) 1998 to 2010. The updated National Cholesterol Education Program criteria was used, which define dyslipidemia as having one or more of the following lipid abnormalities: hypercholesterolemia (total cholesterol ≥240 mg/dL or diagnosis of dyslipidemia or use of lipid-lowering drugs), hypertriglyceridemia (≥150 mg/dL), hyper-low density lipoprotein (LDL) cholesterolemia (≥160 mg/dL or diagnosis of dyslipidemia or use of lipid-lowering drugs), and hypo-high density lipoprotein (HDL)-cholesterolemia (<40 mg/dL in men and <50 mg/dL in women). RESULTS The number of participants was 6,921, 4,894, 5,312, 2,733, 6,295, 6,900, and 5,738 in KNHANES 1998, 2001, 2005, 2007, 2008, 2009, and 2010, respectively. Age-standardized prevalence rates of dyslipidemia were 54.0%, 65.8%, 66.5%, 60.6%, 58.7%, 58.9%, and 59.0% in 1998, 2001, 2005, 2007, 2008, 2009, and 2010, respectively. Hypertriglyceridemia and hypo-HDL-cholesterolemia were the two most frequent lipid abnormalities. The overall prevalence of hypercholesterolemia and hyper-LDL-cholesterolemia increased by 1.36- and 1.35-fold in 2010 compared with 2007, respectively. Awareness, treatment, and control rates of dyslipidemia improved over the period of surveys in both sexes. In 2010, about 30% of dyslipidemic patients who received lipid-lowering treatment reached target levels. CONCLUSION Although the management status of dyslipidemia has improved during recent years, effective strategy is required for achieving better prevention, treatment, and control of dyslipidemia.

Diabetes Epidemics in Korea: Reappraise Nationwide Survey of Diabetes "Diabetes in Korea 2007"

Abstract: There are many studies on the prevalence, clinical characteristics, and economic burden of diabetes across the past four decades in Korea. Nonetheless, there is a dearth of nationwide study regarding diabetes encompassing all age group. Eight years ago, the Committee on the Epidemiology of Diabetes Mellitus of Korean Diabetes Association collaborated with Health Insurance Review & Assessment Service to evaluate the status of diabetes care and characteristics in diabetic patients in Korea. In 2007, the collaborative task force team published a comprehensive survey titled "Diabetes in Korea 2007." In this review, we reappraise the diabetic epidemics from the joint report and suggest further studies that are needed to be investigated in the future.

The Role of Skeletal Muscle in Development of Nonalcoholic Fatty Liver Disease

Abstract: Background: Nonalcoholic fatty liver disease (NAFLD) is closely correlated with abnormal accumulation of visceral fat, but the role of skeletal muscle remains unclear. The aim of this study was to elucidate the role of skeletal muscle in development of NAFLD. Methods: Among 11,116 subjects (6,242 males), we examined the effects of skeletal muscle mass and visceral fat area (VFA, by bioelectric impedance analysis) on NAFLD using by the fatty liver index (FLI). Results: Of the total subjects (9,565 total, 5,293 males) included, 1,848 were classified as having NALFD (FLI ≥60). Body mass index, lipid profile, fasting plasma glucose, hemoglobin A1c, prevalence of type 2 diabetes (DM), hypertension (HTN), and met abolic syndrome were higher in males than females, but FLI showed no significant difference. The low FLI group showed the lowest VFA and highest skeletal muscle mass of all the groups. Skeletal muscle to visceral fat ratio (SVR) and skeletal muscle index had inverse correlations with FLI, when adjusted for age and gender. In multivariate regression analysis, SVR was negatively associated with FLI. Among SVR quartiles, the highest quartile showed very low risk of NAFLD when adjusted for age, gender, lipid profile, DM, HTN, and high sensitivity C-reactive protein from the lowest quartiles (odds ratio, 0.037; 95% confidence in terval, 0.029 to 0.049). Conclusion: Skeletal muscle mass was inversely associated with visceral fat area, and higher skeletal muscle mass may have a beneficial effect in preventing NAFLD. These results suggest that further studies are needed to ameliorate or slow the progression of sarcopenia.

Ruboxistaurin for the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review of Randomized Clinical Trials

Abstract: 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.

Regulation of muscle pyruvate dehydrogenase complex in insulin resistance: effects of exercise and dichloroacetate

Abstract: 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.

Targeting the Peroxisome Proliferator-Activated Receptor-γ to Counter the Inflammatory Milieu in Obesity

Abstract: Adipose tissue, which was once viewed as a simple organ for storage of triglycerides, is now considered an important endocrine organ. Abnormal adipose tissue mass is associated with defects in endocrine and metabolic functions which are the underlying causes of the metabolic syndrome. Many adipokines, hormones secreted by adipose tissue, regulate cells from the immune system. Interestingly, most of these adipokines are proinflammatory mediators, which increase dramatically in the obese state and are believed to be involved in the pathogenesis of insulin resistance. Drugs that target peroxisome proliferator-activated receptor-γ have been shown to possess anti-inflammatory effects in animal models of diabetes. These findings, and the link between inflammation and the metabolic syndrome, will be reviewed here.

Hemoglobin A1c May Be an Inadequate Diagnostic Tool for Diabetes Mellitus in Anemic Subjects

Abstract: 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. Ane mia 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.

Bidirectional screening of tuberculosis patients for diabetes mellitus and diabetes patients for tuberculosis.

Abstract: To assess the feasibility and results of screening diabetes mellitus (DM) patients for tuberculosis (TB) and TB patients for DM within the routine health care setting. Prospective observational study carried out within the Diabetes Centre and Pulmonary Medicine Department from February 2012 to September 2012. The screening for active TB in DM and DM in TB patients is followed as per the guidelines of the Revised National Tuberculosis Control Programme and national programmes in India. Total of 307 patients diagnosed with TB during the study period. Among the TB patients 9.77% were smokers, 19.54% were known cases diabetes, and 15.96% were newly diagnosed cases of diabetes. Total of 4,118 diabetes patients were screened for TB in which 111 patients found to have TB. The strengths of this study are that we implemented screening within the routine health system. It is feasible to screen DM patients for TB resulting in high rates of TB detection.

Effect of treadmill exercise on interleukin-15 expression and glucose tolerance in zucker diabetic Fatty rats.

Abstract: 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.

Clinical Marker of Platelet Hyperreactivity in Diabetes Mellitus

Abstract: Atherothrombotic complications are important causes of morbidity and mortality in diabetic patients. Diabetes has been considered to be a prothrombotic status. Several factors contribute to the prothrombotic condition, such as increasing coagulation, impaired fibrinolysis, endothelial dysfunction, and platelet hyperreactivity. Among the factors that contribute to the prothrombotic status in diabetes, altered platelet function plays a crucial role. Although understanding platelet function abnormalities in diabetes still remains as a challenge, more attention should be focused on platelet function for effective management and the prediction of atherothrombotic events in diabetic patients. This review will provide an overview on the current status of knowledge of platelet function abnormalities and clinical marker of platelet hyperreactivity in patients with diabetes.

Increasing Prevalence of Type 2 Diabetes in a Rural Bangladeshi Population: A Population Based Study for 10 Years

Abstract: BACKGROUND To observe changes in the prevalence of type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG) and its associated risk factors in a rural Bangladeshi population over a 10-year period. METHODS Three cross-sectional studies were undertaken in a rural community (aged ≥20 years) in 1999, 2004, and 2009. Structured questionnaires including sociodemographic parameters, anthropometric measurements, blood pressure, and blood glucose values were recorded. DM and IFG were diagnosed using 1999 World Health Organization criteria. RESULTS Age standardized prevalence of DM increased significantly (P<0.001) from 1999 to 2009 (2.3%, 6.8%, and 7.9% in 1999, 2004, and 2009, respectively). The prevalence of IFG increased significantly (P=0.011) from 4.6% to 5.8% between 1999 and 2004 but then decreased from 5.8% to 5.3% during 2004 to 2009. Significant linear trends were shown in both sexes for general and central obesity as indicated by body mass index, waist circumference, and waist hip ratio (WHR). Increasing age and systolic blood pressure were significant risk factors for DM in all three studies. WHR for males was also significantly associated with the risk of DM in all three studies. WHR for females was only significantly associated with DM in 2009. CONCLUSION A significant rise in the prevalence of DM was observed in this population over 10 years. This increase was seen in both sexes, and in all age groups. A significant increase in the prevalence of the associated risk factors of general and central obesity was observed in both sexes.

The Mechanism of White and Brown Adipocyte Differentiation

Abstract: Obesity gives vent to many diseases such as type 2 diabetes, hypertension, and hyperlipidemia, being considered as the main causes of mortality and morbidity worldwide. The pathogenesis and pathophysiology of metabolic syndrome can well be understood by studying the molecular mechanisms that control the development and function of adipose tissue. In human body, exist two types of adipose tissue, the white and the brown one, which are reported to play various roles in energy homeostasis. The major and most efficient storage of energy occurs in the form of triglycerides in white adipose tissue while brown adipose tissue actively participates in both basal and inducible energy consumption in the form of thermogenesis. Recent years have observed a rapid and greater interest towards developmental plasticity and therapeutic potential of stromal cells those isolated from adipose tissue. The adipocyte differentiation involves a couple of regulators in the white or brown adipogenesis. Peroxisome proliferators-activated receptor-γ actively participates in regulating carbohydrate and lipid metabolism, and also acts as main regulator of both white and brown adipogenesis. This review based on our recent research, seeks to highlight the adipocyte differentiation.

Effects of Exercise Alone on Insulin Sensitivity and Glucose Tolerance in Obese Youth

Abstract: As with the dramatic increases in childhood obesity over the past decades, the incidence of type 2 diabetes has increased among children and adolescents in the United States. Insulin resistance is a common feature of childhood obesity and increases the risk of type 2 diabetes, metabolic syndrome, and atherogenic lipoprotein profile in obese youth. Although cross-sectional studies report beneficial effects of physical activity or cardiorespiratory fitness on insulin sensitivity, the role of regular exercise alone (e.g., no calorie restriction) as a strategy to reduce the risk of type 2 diabetes is unclear in obese children and adolescents. In this mini review, we examined the independent effects of various exercise on glucose tolerance and insulin sensitivity in obese youth.

The Interplay between Autophagy and Aging

Abstract: 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.

The effects of green tea on obesity and type 2 diabetes.

Abstract: Obesity and type 2 diabetes are major public health issues worldwide, contributing to increased cardiovascular morbidity and mortality. The proportions of people with obesity and/or type 2 diabetes have increased and recently reaching epidemic levels in Asia [1]. Although pharmacologic modality is the mainstay treatment of diabetes, remedies using plants (e.g., garlic, psyllium, and green tea) have stimulated a new interest in research [2]. Green tea (Camellia sinensis) is one of the world's most popular beverages, especially in Asian countries including Korea, China, and Japan. Because of the high rate of green tea consumption in these populations, even small effects on an individual basis could have a large public health impact [3]. A population-based, prospective cohort study has shown that green tea consumption is associated with reduced mortality due to all causes and cardiovascular disease as well [4], and randomized controlled trials have indicated that green tea is effective in decreasing blood pressure, low density lipoprotein cholesterol, oxidative stress, and a marker of chronic inflammation [5]. Various studies have shown the beneficial effects of green tea, not only on cardiovascular diseases but also on obesity and type 2 diabetes itself [6,7]. In a retrospective cohort study performed in Japan, a 33% risk reduction of developing type 2 diabetes was found in subjects consuming six or more cups of green tea daily compared to those consuming less than 1 cup per week [6]. Wu et al. [7] reported that Taiwanese subjects who had habitually consumed tea for more than 10 years showed lower body fat composition and smaller waist circumference. Evidences from epidemiological studies suggest the possibility of green tea being a novel strategy for treatment or prevention of obesity and diabetes. However, a limited number of clinical trials using green tea, green tea extracts (GTEs), or its main ingredient catechin have shown disappointing results in controlling hyperglycemia in type 2 diabetic patients or protecting the condition in healthy subjects. MacKenzie et al. [8] showed no significant difference in glucose control after 3 months of ingestion of decaffeinated GTE in type 2 diabetic patients in a double-blinded, placebo-controlled, randomized trial. Similarly, Nagao et al. [9] showed that plasma glucose levels and A1c did not improve after 12 weeks of supplementation with catechin in patients with type 2 diabetes [9]. However, they showed that the addition of catechin decreased A1c level and increased serum insulin level compared to the placebo group in a subgroup of patients who have been treated with insulin therapy. Also, Hsu et al. [10] showed no difference in glycemic control or lipid parameters after 16 weeks of green tea supplementation. Ryu et al. [11] showed that 4 weeks of green tea consumption did not affect inflammation, adiponectin levels, or insulin resistance in type 2 diabetic patients, and they suggested that those mechanisms were unlikely to explain the benefits in cardiovascular risk or mortality by tea consumption observed in epidemiological studies. Despite these equivocal results, several mechanisms have been proposed to explain the positive effect of green tea on glucose metabolism or obesity. Epigallocatechin gallate (EGCG), the most abundant form of catechin in green tea, has been known to be the main attributable factor of beneficial effects of green tea [12]. EGCG inhibits adipocyte proliferation and differentiation in 3T3-L1 cells [13], increases fat oxidation [14], and increases expression of GLUT-4 in adipose tissue of an animal model [15]. In human studies, clear increases in energy expenditure were documented [16]. Also, some suggested the protective function of EGCG for cytokine-induced β-cell destruction mediated by inhibition of nuclear factor-κB activation [17]. Recently, Tian et al. [18] showed that green tea polyphenols had antiobesity effect by up-regulating adiponectin levels in rats. They suggested that the involved mechanisms were the inhibition of Erk activation, alleviation of peroxisome proliferator-activated receptor γ (PPARγ) phosphorylation, and increases in the PPARγ expression [18]. Park et al. [19] revealed the ambivalent role of gallated catechin (GC) in green tea, including EGCG, in glucose tolerance. GC acutely reduces blood glucose levels mainly through its activities in the alimentary tract while increasing the glucose level when in the circulation by blocking normal glucose uptake into the tissues. They suggested the development of nonabsorbable derivatives of GC with only positive luminal effect as a prevention strategy of type 2 diabetes and obesity. As mentioned above, many researches are being performed to define the precise molecular mechanisms of green tea and ultimately, its clinical application in obesity and type 2 diabetes. In this study, Bae and his colleagues [20] demonstrated the possibility of GTE as an antiobestic and/or antidiabetic agent when coadministered with another dietary supplement poly-γ-glutamic acid (γ-PGA) in db/db mice, potentially through the action of intestinal GTE. γ-PGA is a main constituent of the viscous material in Korean chungkookjang and Japanese natto. The study presents the results of nuclear magnetic resonance spectroscopy that γ-PGA can interact with EGCG, and this possible complex formation may delay the absorption of GCs to systemic circulation from the intestine, resulting in decreased blood glucose level. The protective effects of GTE+γ-PGA regimen on body weight gain and development of glucose intolerance were much better than treatment with either GTE or γ-PGA alone. Therefore, they suggest that GTE+γ-PGA treatment may be a promising preventative and therapeutic tool for obesity and type 2 diabetes. Future studies, especially in human, are warranted to confirm these benefits in patients with diabetes or healthy subjects, as well as to define the precise molecular mechanisms of action of green tea supplementation.

Cell Therapy for Diabetic Neuropathy Using Adult Stem or Progenitor Cells

Abstract: Diabetic neuropathy (DN) is the most common and disabling complication of diabetes that may lead to foot ulcers and limb amputations. Despite widespread awareness of DN, the only effective treatments are glucose control and pain management. A growing body of evidence suggests that DN is characterized by reduction of vascularity in peripheral nerves and deficiency in neurotrophic and angiogenic factors. Previous studies have tried to introduce neurotrophic or angiogenic factors in the form of protein or gene for therapy, but the effect was not significant. Recent studies have shown that bone marrow (BM)-derived stem or progenitor cells have favorable effects on the repair of cardiovascular diseases. Since these BM-derived stem or progenitor cells contain various angiogenic and neurotrophic factors, these cells have been attempted for treating experimental DN, and turned out to be effective for reversing various manifestations of experimental DN. These evidences suggest that cell therapy, affecting both vascular and neural components, can represent a novel therapeutic option for treatment of clinical DN.

Beneficial Effects of Omega-3 Fatty Acids on Low Density Lipoprotein Particle Size in Patients with Type 2 Diabetes Already under Statin Therapy.

Abstract: Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C), additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (≥200 mg/dL) while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL) particle size and triglyceride (TG) level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%±3.1% vs. 2.3%±3.6%, P=0.024; -41.0%±24.1% vs. -24.2%±31.9%, P=0.049). Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects.

Diabetic Retinopathy and Endothelial Dysfunction in Patients with Type 2 Diabetes Mellitus

Abstract: BACKGROUND We investigated the relationship between endothelial dysfunction and diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS We used a cross-sectional design to examine 167 patients with type 2 diabetes mellitus. All patients underwent biochemical and ophthalmological examination. We assessed endothelial dysfunction by a flow-mediated vasodilation method of the brachial artery. Changes in vasodilation (flow-mediated vasodilatation, %FMD) were expressed as percent change over baseline values. RESULTS The mean±standard deviation of patient age was 54.1±8.6 years. The %FMD was significantly lower in patients with DR than without DR. The prevalence of retinopathy decreased across increasing tertiles of %FMD. After adjusting for patients' age, sex, diabetes duration, use of insulin, use of antihypertensive, antiplatelet, and lipid lowering medications, systolic blood pressure, fasting plasma glucose, 2-hour plasma glucose, glycated hemoglobin, and urinary albumin excretion, participants with a reduced %FMD were more likely to have DR (odds ratio, 11.819; 95% confidence interval, 2.201 to 63.461; P=0.004, comparing the lowest and highest tertiles of %FMD). CONCLUSION Endothelial dysfunction was associated with DR, which was most apparent when the endothelial dysfunction was severe. Our study provides insights into the possible mechanism of the influence of endothelial dysfunction on the development of DR.

Low Levels of Physical Activity Are Associated with Increased Metabolic Syndrome Risk Factors in Korean Adults

Abstract: Background: Low levels of physical activity (PA) are strongly associated with the development of metabolic syndrome (MetS) and chronic diseases. However, few studies have examined this association in Koreans. The primary purpose of this study was to examine the associations between PA and MetS risks in Korean adults. Methods: A total of 1,016 Korean adults (494 males and 522 females) participated in this study. PA levels were assessed using the International PA Questionnaire. MetS risk factors were determined using clinically established diagnostic criteria. Results: Compared with the highest PA group, the group with the lowest level of PA was at greater risk of high triglyceride (TG) in males (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.07 to 3.24) and of hemoglobin A1c ≥5.5% in females (OR, 1.75; 95% CI, 1.00 to 3.04) after adjusting for age and body mass index. Compared with subjects who met the PA guidelines, those who did not meet the guidelines were more likely to have low high density lipoprotein cholesterol in both males (OR, 1.69; 95% CI, 1.11 to 2.58), and females (OR, 1.82; 95% CI, 1.20 to 2.77). Furthermore, those who did not meet the PA guidelines were at increased risk of high TG levels in males (OR, 1.69; 95% CI, 1.23 to 2.86) and abnormal fasting glucose (OR, 1.93; 95% CI, 1.17 to 3.20) and MetS (OR, 2.10; 95% CI, 1.15 to 3.84) in females. Conclusion: Increased levels of PA are significantly associated with a decreased risk of abnormal MetS components.

Subclinical Hypothyroidism Is Independently Associated with Microalbuminuria in a Cohort of Prediabetic Egyptian Adults

Abstract: Background: Recent evidence has suggested an association between subclinical hypothyroidism (SCH) and microalbuminuria in patients with type 2 diabetes. However, whether SCH is related to microalbuminuria among subjects with prediabetes has not been studied. Thus, we evaluated the association between SCH and microalbuminuria in a cohort of prediabetic Egyptian adults. Methods: A total of 147 prediabetic subjects and 150 healthy controls matched for age and sex were enrolled in this study. Anthropometric measurements, plasma glucose, lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR), thyroid stimulating hormone (TSH), free thyroxine, triiodothyronine levels, and urinary albumin-creatinine ratio (UACR) were assessed. Results: The prevalence of SCH and microalbuminuria in the prediabetic subjects was higher than that in the healthy controls (16.3% vs. 4%, P<0.001; and 12.9% vs. 5.3%, P=0.02, respectively). Prediabetic subjects with SCH were characterized by signifi cantly higher HOMA-IR, TSH levels, UACR, and prevalence of microalbuminuria than those with euthyroidism. TSH level was associated with total cholesterol (P=0.05), fasting insulin (P=0.01), HOMA-IR (P=0.01), and UACR (P=0.005). UACR was associated with waist circumference (P=0.01), fasting insulin (P=0.05), and HOMA-IR (P=0.02). With multiple logistic regression analysis, SCH was associated with microalbuminuria independent of confounding variables (β=2.59; P=0.01). Conclusion: Our findings suggest that prediabetic subjects with SCH demonstrate higher prevalence of microalbuminuria than their non-SCH counterparts. SCH is also independently associated with microalbuminuria in prediabetic subjects. Screening and treatment for SCH may be warranted in those patients.