Application of Animal Models in Diabetic Cardiomyopathy

Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.

Application of Animal Models in Diabetic Cardiomyopathy

Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.

Diabetic cardiomyopathy: where we are and where we are going

The global burden of diabetes mellitus and its related complications are currently increasing. Diabetes mellitus affects the heart through various mechanisms including microvascular impairment, metabolic disturbance, subcellular component abnormalities, cardiac autonomic dysfunction, and a maladaptive immune response. Eventually, diabetes mellitus can cause functional and structural changes in the myocardium without coronary artery disease, a disorder known as diabetic cardiomyopathy (DCM). There are many diagnostic tools and management options for DCM, although it is difficult to detect its development and effectively prevent its progression. In this review, we summarize the current research regarding the pathophysiology and pathogenesis of DCM. Moreover, we discuss emerging diagnostic evaluation methods and treatment strategies for DCM, which may help our understanding of its underlying mechanisms and facilitate the identification of possible new therapeutic targets.

Glycemic Targets for the Critically Ill Patient / 임상당뇨병

Critically ill patients often experience hyperglycemia, which may be associated with increased morbidity and mortality. In 2001, van den Berghe et al. suggested significant benefit of normalization of blood glucose level in critically ill patients using intensive intravenous insulin therapy. Subsequent multicenter randomized studies, however, demonstrated adverse effects of tight glucose control. Therefore, while the need for glucose control in critically ill patients is generally accepted, the treatment thresholds for initiation of insulin therapy or target glucose values are still undetermined. Furthermore, occurrence of a hypoglycemic event during intensive insulin therapy is known to be an independent predictor of clinical outcome, and glycemic variability is an important variable of glucose management in the critically ill patients. Novel technological approaches such as a continuous glucose monitoring system (CGMS) might help to overcome some problems of tight glucose control by reducing the risk of hypoglycemia and minimizing glycemic variability.

Prevalence and Gender-Related Characteristics of Metabolic Syndrome in Korean Community

OBJECTIVE: There are still a limited number of studies assessing the prevalence of metabolic syndrome in the community. The aim of this study is to investigate the prevalence and gender-related characteristics of metabolic syndrome in Korean community. METHODS: A total of 417 community subjects (mean age was 60.7+/-13.6 years, 35.3% were men) who attended the routine check-up were analyzed. National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP) III clinical guideline was used to define metabolic syndrome. RESULTS: Metabolic syndrome was diagnosed in 38.1% of study subjects. The prevalence of metabolic syndrome was not different between men and women (men 39.0% vs. women 37.5%, p=0.766). The positive association between age and the prevalence of metabolic syndrome was more pronounced in women (chi2=17.52, p for trend or =50 years). The most prevalent factor of metabolic syndrome was hypertriglyceridemia (49.9%) and hypertension (47.6%) in both genders. Among metabolic syndrome components, central obesity (40.5% vs. 25.2%, p=0.002) and hypertriglyceridemia (54.5% vs. 41.8%, p=0.015) were more prevalent in women than in men, and the prevalence of other components were similar between genders. CONCLUSIONS: In the community, metabolic syndrome was highly prevalent in middle-aged and elderly Korean adult. Age related change in the prevalence of metabolic syndrome was gender specific. Age and gender effects should be considered for the effective control of metabolic syndrome in the community.

A Case of Teriparatide on Pregnancy-Induced Osteoporosis

Pregnancy-induced osteoporosis is a rare disorder characterized by fragility fracture and low bone mineral density (BMD) during or shortly after pregnancy, and its etiology is still unclear. We experienced a case of a 39-year-old woman who suffered from lumbago 3 months after delivery. Biochemical evidence of increased bone resorption is observed without secondary causes of osteoporosis. Radiologic examination showed multiple compression fractures on her lumbar vertebrae. We report a case of patient with pregnancy-induced osteoporosis improved her clinical symptom, BMD and bone turnover marker after teriparatide therapy.

The Effects of Green Tea on Obesity and Type 2 Diabetes

No abstract available.

Nutritional Status and Cardiac Autophagy

Autophagy is necessary for the degradation of long-lasting proteins and nonfunctional organelles, and is activated to promote cellular survival. However, overactivation of autophagy may deplete essential molecules and organelles responsible for cellular survival. Lifelong calorie restriction by 40% has been shown to increase the cardiac expression of autophagic markers, which suggests that it may have a cardioprotective effect by decreasing oxidative damage brought on by aging and cardiovascular diseases. Although cardiac autophagy is critical to regulating protein quality and maintaining cellular function and survival, increased or excessive autophagy may have deleterious effects on the heart under some circumstances, including pressure overload-induced heart failure. The importance of autophagy has been shown in nutrient supply and preservation of energy in times of limitation, such as ischemia. Some studies have suggested that a transition from obesity to metabolic syndrome may involve progressive changes in myocardial inflammation, mitochondrial dysfunction, fibrosis, apoptosis, and myocardial autophagy.

Letter: Higher Glycated Hemoglobin Level Is Associated with Increased Risk of Ischemic Stroke in Non-Diabetic Korean Male Adults (Diabetes Metab J 2011;35:551-7)

No abstract available.

The Peroxisome Proliferator-Activated Receptor delta Agonist, GW501516, Inhibits Angiogenesis through Dephosphorylation of Endothelial Nitric Oxide Synthase

OBJECTIVE: Peroxisome proliferator-activated receptor delta (PPAR-delta) is an ubiquitously expressed nuclear receptor that has been implicated in adipose tissue formation, brain development, and atherosclerosis. Despite mouse studies demonstrating that PPAR-delta activation has favorable anti-atherogenic properties by improving systemic lipid profiles, the relationship between PPAR-delta agonist and angiogenesis is unknown. We hypothesized that PPAR-delta ligands modulate the angiogenesis. METHODS: To test this hypothesis we treated primary cultures of bovine aortic endothelial cells with PPAR-delta specific ligand, GW501516 (50-800 nM) for 6 h. RESULTS: GW501516 dose-dependently decreased nitric oxide production without alteration in endothelial nitric oxide synthase (eNOS) expression. Analysis with phospho-specific antibodies against eNOS demonstrated that GW501516 significantly decreased the phosphorylation of eNOS at Serine1179 (eNOS-Ser1179). Concurrently, GW501516 also decreased the Akt phosphorylation. GW501516 did not affect endothelial cell proliferation or induce apoptosis. However, GW501516 inhibited endothelial cell migration, and tube formation in a high nanomolar concentration. The inhibition of endothelial cell tube formation by GW501516 was prevented by addition of the nitric oxide donor, DETA NONOate (5 microM). GW501516 was also found to inhibit angiogenesis in vivo in the chicken chorioallantoic membrane assay. CONCLUSION: These results provide that high nanomolar range of GW501516 inhibits angiogenesis by a mechanism involving dephosphorylation of eNOS-Ser1179.

A Case of Diabetic Mastopathy

Diabetic mastopathy is an unusual fibroinflammatory breast lesion that is characteristically presented in premenopausal women with long-standing diabetes with multiple microvascular complications. This patient was a 49-year-old postmenopausal woman with diabetic nephropathy, neuropathy, and retinopathy. Although palpable mass was detected on the left breast, an ultrasonography could not distinguish it from breast cancer. Excisional biopsy was conducted. Histological findings indicated diabetic mastopathy with keloid-like fibrosis, perivascular lymphocytic infiltration, and lymphocytic lobulitis without evidence of malignancy. After excision, there has been no recurrence until now.

Medical Therapy in Pregnant Women with Diabetes / 임상당뇨병

Pregnant women with diabetes are at greater risk for adverse outcomes, such as miscarriage, macrosomia, and preterm birth. Advances in the care of diabetes have reduced maternal and perinatal mortality rates to the levels expected in nondiabetic pregnancies. Lifestyle modification such as medical nutritional therapy and exercise is a first step in therapy for gestational diabetes. Rapid-acting insulin analogs (lispro, aspart) are comparable in safety and superior in glucose control to regular human insulin. Because the safety of long-acting insulin analogs (glargine, detemir) in pregnancy has not firmly established, the use of human insulin is preferred over basal insulin. Among the oral hypoglycemic agents, metformin and glyburide might be considered as alternative therapies.

Exercise in Patients with Advanced Diabetic Complications / 임상당뇨병

Structured exercise is considered as an important cornerstone to achieve good glycemic control and improve cardiovascular risk profile in diabetes. Both aerobic and resistance training improve insulin action and can assist with management of blood glucose levels, lipids, and blood pressure. However, exercise must be undertaken regularly to have continued benefits and include regular training varying types. Most persons with diabetic complication such as vascular disease, peripheral neuropathy, autonomic neuropathy, retinopathy, and nephropathy can perform exercise safely as long as certain precautions are taken.

A case of papillary thyroid cancer and pheochromocytoma with ganglioneuroma / 대한내과학회지

Composite tumors containing pheochromocytoma and ganglioneuroma are very rare. We report a 70-year-old female with papillary thyroid carcinoma and a compound adrenal medullary tumor, composed of pheochromocytoma/ ganglioneuroma. She had complained of epigastric discomfort 2 months earlier. Chest computed tomography and pancreatic magnetic resonance imaging revealed an intrathoracic goiter and pancreatic cystic tumor. She underwent an explorative laparotomy, and a left adrenalectomy was done because of an adrenal mass, not the pancreatic mass. The pathological diagnosis was a compound adrenal medullary tumor, composed of pheochromocytoma and ganglioneuroma. Although there was no evidence of thyroid cancer on fine needle aspiration cytology, a total thyroidectomy was done because of the neck discomfort. The pathological diagnosis was a papillary thyroid carcinoma, and she underwent radioactive iodine therapy.

Prevalence of the Metabolic Syndrome in Type 2 Diabetic Patients / 당뇨병

BACKGROUND: The aim of this study was to analyze the prevalence of metabolic syndrome in Korean type 2 diabetic patients. METHODS: A total of 4,240 diabetic patients (male 2,033, female 2,207; mean age 58.7 +/- 11.3 years; DM duration 8.9 +/- 7.6 years) were selected from the data of endocrine clinics of 13 university hospitals in 2006. Metabolic syndrome was defined using the criteria of the American Heart Association/National Heart Lung and Blood Institute and the criteria of waist circumference from the Korean Society for the Study of Obesity. RESULTS: The prevalence of metabolic syndrome was 77.9% (76.7% of males, 78.9% of females). The average number of the components of metabolic syndrome was 2.4 +/- 1.1. Abdominal obesity was seen in 56.8% of the patients, hypertriglyceridemia in 42.0%, low HDL cholesterol in 65.1%, and high blood pressure in 74.9%. Abdominal obesity and high blood pressure were much more prevalent among females than males, and low HDL cholesterol was much more prevalent among males than females. The prevalence of metabolic syndrome was not different according to the duration of diabetes. Metabolic syndrome was strongly related with obesity (odds ratio, 6.3) and increased age (odds ratio in the over 70 group, 3.4). CONCLUSION: The prevalence of metabolic syndrome was 77.9% in Korean type 2 diabetic patients. Its prevalence was greater in obese patients and in those over 40 years of age.

A Nationwide Survey about the Current Status of Glycemic Control and Complications in Diabetic Patients in 2006: The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus / 당뇨병

BACKGROUND: The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus performed a nationwide survey about the current status of glycemic control and diabetic complications in 2006. METHODS: The current study included 5,652 diabetic patients recruited from the rosters of endocrinology clinics of 13 tertiary hospitals in Korea. Age, gender, height, weight, waist circumference and blood pressure were investigated by standard method. Fasting and postprandial 2 hour glucose, glycosylated hemoglobin (HbA1c), lipid profiles, fasting insulin and c-peptide levels were measured. Microvascular (microalbuminuria, retinopathy and neuropathy) and macrovascular (coronary artery disease [CAD], cerebrovascular disease [CVD] and peripheral artery disease [PAD]) complications were reviewed in their medical records. RESULTS: Mean age of total subjects was 58.7 (+/- 11.6) years and duration of diabetes was 8.8 (0~50) years. Mean fasting and postprandial 2 hour glucose levels were 145.9 +/- 55.0 and 208.0 +/- 84.4 mg/dL, respectively. Their mean HbA1c was 7.9 +/- 1.9%: the percentage of patients within target goal of glycemic control (< 7% of HbA1c) was 36.7%. In this study, 30.3%, 38.3% and 44.6% of patients was found to have microalbuminuria, retinopathy and nephropathy, respectively. Prevalence of CAD, CVD and PAD was 8.7%, 6.7% and 3.0%, respectively. Diabetic complications were closely related with age, duration of diabetes and glycemic control, and this relationship was stronger in microvascular complications than macrovascular ones. CONCLUSION: Only about one third of patients with diabetes was found to reach target glycemic control in tertiary hospitals of Korea. More tight control is needed to reduce deleterious complications of diabetes in Korea.

Association of Non-alcoholic Fatty Liver Disease with Insulin Resistance in Non-Diabetic, Normal Weight Adults / 대한내과학회지

BACKGROUND: It is well known that non-alcoholic fatty liver disease is associated with type 2 diabetes mellitus, obesity, and dyslipidemia. Non-alcoholic fatty liver disease is frequently found in non-diabetic, normal weight adults, but the meaning of it is not fully investigated. We tested the hypothesis that there is association between non-alcoholic fatty liver disease with insulin resistance in non-diabetic, normal weight adults. METHODS: We examined 60 Korean adults above the age of 30 years, participating in medical check-up at the Chung-Ang University Hospital, from Sep 2003 to Jan 2004. Heapatitis B and C serologies were negative, and not the history of alcohol abuse. A standard interview, physical exam and biochemical study were conducted, and an experienced operator carried out ultrasound liver studies. We assessed the clinical characteristics of subjects and HOMA (Homeostasis Model Assessment), QUICKI (Quantitative Insulin Sensitivity Check Index) as an index of insulin resistance. RESULTS: We classified subjects into 2 groups: the controls (n=42), and those with non-alcoholic fatty liver disease (n=18). The frequency in the men was higher than that in the women (70 vs 30 %, p<0.05). Body mass index, waist circumference, hip circumference, waist/hip ratio, triglyceride, HDL-cholesterol, alanine transferase, and uric acid was significantly different between two groups (p<0.05). Insulin resistance (HOMA-IR) was significantly higher in subjects with non-alcoholic fatty liver disease (p<0.05). CONCLUSION: Non-alcoholic fatty liver disease is associated with insulin resistance in non- diabetic, normal weight adults.

Methylglyoxal Induces Apoptosis Mediated by Reactive Oxygen Species in Bovine Retinal Pericytes

One of the histopathologic hallmarks of early diabetic retinopathy is the loss of pericytes. Evidences suggest that the pericyte loss in vivo is mediated by apoptosis. However, the underlying cause of pericyte apoptosis is not fully understood. This study investigated the influence of methylglyoxal (MGO), a reactive -dicarbonyl compound of glucose metabolism, on apoptotic cell death in bovine retinal pericytes. Analysis of internucleosomal DNA fragmentation by ELISA showed that MGO (200 to 800 micrometer) induced apoptosis in a concentration-dependent manner. Intracellular reactive oxygen species were generated earlier and the antioxidant, N-acetyl cysteine, inhibited the MGO-induced apoptosis. NF-kB activation and increased caspase- 3 activity were detected. Apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF- kB inhibitor, pyrrolidine dithiocarbamate. These data suggest that elevated MGO levels observed in diabetes may cause apoptosis in bovine retinal pericytes through an oxidative stress mechanism and suggests that the nuclear activation of NF-kB are involved in the apoptotic process.

Perception of Risk of Developing Diabetes in Offspring of Type 2 Diabetic Patients

BACKGROUND: The risk of developing diabetes is high in the offspring of patients with type 2 diabetes. There have been no studies to assess the offspring's awareness of the risk of developing diabetes. The aim of this study was to investigate how the male offspring of type 2 diabetic patients assess their likelihood of developing diabetes. METHODS: One hundred and one non-diabetic men with one or both parents having type 2 diabetes, aged 19-28 years, were recruited. RESULTS: Thirty-nine subjects (38.6%) were concerned about diabetes and 85 (84.2%) considered diabetes a serious problem. However, only 10 (9.9%) thought they might develop diabetes and 9 (8.9%) had previously attended diabetes education programs with their parents. The educational level amongst the diabetic parents was the only independent predictor of perception of the increased risk. Age, body mass index, waist-to-hip ratio, educational level and the perception of diabetes as a serious problem were not associated with perception of the increased risk. CONCLUSION: Most offspring of diabetic parents lacked knowledge about the increased risk amongst family members. We suggest that physicians and diabetic educators should provide knowledge about the increased risk of developing diabetes in offspring and the benefit of lifestyle modification to delay or prevent the development of the disease.

Insulin Secretion and Sensitivity during Oral Glucose Tolerance Test in Korean Lean Elderly Women

Impaired glucose tolerance (IGT) and type 2 diabetes including undiagnosed isolated postchallenge hyperglycemia (IPH) are common in the elderly. The aim of this study was to investigate the insulin secretion and sensitivity in Korean elderly lean diabetic women. Forty-one lean women aged 65-88 years took 2 hr oral glucose tolerance test (OGTT) and were stratified according to the WHO criteria (normal glucose tolerance [NGT], n=20; IGT, n=6; and type 2 diabetics, n=15 including seven IPH). HbA1c and fructosamine progressively increased from the NGT to the diabetic subjects (p=0.006 and p=0.001, respectively). Compared with subjects with NGT, the insulinogenic index, a marker of early insulin secretion and the AUCins, a marker of total insulin secretion, decreased significantly in diabetic group [0.53 (-0.44 -1.45) vs. 0.18 (0.00 -1.11), p=0.03 and 306 +/- 165 vs. 199 +/- 78 pmol/L, p=0.02 respectively]. A significant difference was found in the AUCc-peptide among each group (221 +/- 59 vs. 206 +/- 34 vs. 149 +/- 51 pmol/L, p=0.001 for each). The homeostasis model assessment of insulin resistance (HOMA-IR), a marker of insulin resistance, was not different among the groups. We conclude that compared with NGT subjects, elderly lean women with diabetes have impaired oral glucose-induced insulin secretion but have relatively preserved insulin sensitivity. This suggests that insulin resistance is not necessarily an essential component of Korean elderly lean diabetic women.