Eun Shil Hong

Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity

Obesity is associated with infiltration of macrophages into adipose tissue (AT), contributing to insulin resistance and diabetes. However, relatively little is known regarding the origin of AT macrophages (ATMs). We discovered that murine models of obesity have prominent monocytosis and neutrophilia, associated with proliferation and expansion of bone marrow (BM) myeloid progenitors. AT transplantation conferred myeloid progenitor proliferation in lean recipients, while weight loss in both mice and humans (via gastric bypass) was associated with a reversal of monocytosis and neutrophilia. Adipose S100A8/A9 induced ATM TLR4/MyD88 and NLRP3 inflammasome-dependent IL-1β production. IL-1β interacted with the IL-1 receptor on BM myeloid progenitors to stimulate the production of monocytes and neutrophils. These studies uncover a positive feedback loop between ATMs and BM myeloid progenitors and suggest that inhibition of TLR4 ligands or the NLRP3-IL-1β signaling axis could reduce AT inflammation and insulin resistance in obesity.

Comparison between sitagliptin as add-on therapy to insulin and insulin dose-increase therapy in uncontrolled Korean type 2 diabetes: CSI study

Aim: Individuals requiring insulin therapy for type 2 diabetes often require escalation of their regimen to achieve glycaemic control. Optimal management strategies for uncontrolled type 2 diabetes would improve glycaemic control without hypoglycaemia and weight gain. This study compared the efficacy and tolerability of adding sitagliptin, an oral dipeptidyl peptidase‐4 inhibitor, and an up to 20% increase in insulin dose in patients with uncontrolled type 2 diabetes on insulin therapy.

Clinical Implications of Adipocytokines and Newly Emerging Metabolic Factors with Relation to Insulin Resistance and Cardiovascular Health

Adipose tissue is known to secrete hormones actively and produces many biologically active proteins called adipocytokines. Typically, obesity is followed by low-grade inflammation, which is characterized by increased circulating levels of pro-inflammatory cytokines. Macrophages play a role in the inflammatory process by secreting many cytokines such as tumor necrosis factor alpha, interleukin-6, resistin, and retinol binding protein-4. These cytokines and chemokines participate in low-grade pro-inflammatory processes leading to insulin resistance, metabolic impairment, and cardiovascular diseases. More metabolic regulators, such as fibroblast growth factor (FGF)21, FGF19, FGF1, vaspin, and visfatin have now been discovered but their exact roles in human diseases are still unclear. This review focuses on recent research regarding the role of adipokines and new metabolic factors in metabolic derangement or cardiovascular disease.

Counterintuitive relationship between visceral fat and all-cause mortality in an elderly Asian population.

Abdominal obesity is considered to be a risk factor for mortality. However, recent studies indicate that overweight may be negatively associated with mortality (“obesity paradox”). The relationships between mortality and various obesity markers in an elderly Asian cohort were evaluated.

PROPIT: A PROspective comparative clinical study evaluating the efficacy and safety of PITavastatin in patients with metabolic syndrome.

Dyslipidaemia and central obesity are the major factors underlying the dramatic increase in metabolic syndrome (MS). We compared the effects of early combined therapy with pitavastatin and intensive lifestyle modification (LSM) on the amelioration of each component of MS with those of LSM only.

The amount of C1q–adiponectin complex is higher in the serum and the complex localizes to perivascular areas of fat tissues and the intimal–medial layer of blood vessels of coronary artery disease patients

BackgroundThe complement component C1q triggers activation of the classical immune pathway and can bind to adiponectin (APN). Recently, some studies have been reported that serum C1q-APN/total APN ratio correlates with atherosclerosis and coronary artery disease (CAD). We assessed the relationships between C1q related variables and the severity of CAD, and investigated the localization of the C1q–APN complex.MethodsThe sample included 153 subjects comprising healthy controls and patients with subclinical or overt CAD. We measured the serum concentrations of C1q, total APN, and high-molecular weight (HMW)-APN, and the amount of C1q–APN complex. We identified the sites of C1q–APN complex deposition in various adipose tissues and blood vessels.ResultsSerum concentrations of C1q and HMW-APN and the C1q/HMW-APN ratio were independently associated with the severity of coronary stenosis. The amount of C1q–APN complex was significantly higher in patients with CAD compared with controls. C1q and APN co-localized in perivascular areas of subcutaneous, visceral, and pericardial fat tissues, and the internal mammary artery of patients with severe CAD.ConclusionsSerum C1q concentration and the C1q/HMW-APN ratio were independent markers of coronary artery stenosis. The amount of C1q–APN complex was significantly greater in serum from CAD patients. C1q and APN co-localized to perivascular areas in adipose tissue and blood vessels. The association between the increased amount of the C1q–APN complex and CAD should be investigated further.

Effect of carnitine-orotate complex on glucose metabolism and fatty liver: A double-blind, placebo-controlled study

Effective medicines have not been introduced for insulin resistance‐related fatty liver. The efficacy and safety of treatment between a combination of metformin and carnitine‐orotate complex and metformin alone in a 12‐week, double‐blind, randomized, placebo‐controlled study on drug‐naïve patients with impaired glucose metabolism and fatty liver were compared.

Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes

AIMS The clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes. METHODS We recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3-6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7-6.4%, 39-46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated. RESULTS Eighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥ 165 mg/dL and a 30-min C-peptide < 5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98-26.16) of developing diabetes than other prediabetic subjects. CONCLUSIONS In Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population.

Associations between thyroid hormone levels and regional fat accumulation in euthyroid men

OBJECTIVE Body adiposity, especially ectopic fat accumulation, has a range of metabolic and cardiovascular effects. This study aimed to investigate whether thyroid function is associated with various regional fat quantities in euthyroid subjects. METHODS A total of 100 euthyroid men (free triiodothyronine (fT3), 4.77±1.21 pg/ml; free thyroxine (fT4), 1.38±0.21 ng/dl; and TSH, 2.09±0.91 μIU/ml) were enrolled in this cross-sectional study. We measured accumulated regional fat using 64-slice multi-detector computed tomography. Multiple linear regression analysis was used to determine whether accumulated fat in each region was associated with clinical parameters after adjusting for age. RESULTS FT3 was inversely correlated with BMI (R=0.232, P=0.029) and LDL cholesterol level (R=0.277, P=0.019). FT4 was inversely correlated with waist circumference (R=0.350, P=0.008) and BMI (R=0.355, P0.001). In multiple linear regression analysis, fT3 and fT4 levels were significantly associated with pericardial fat volume (fT3: B=-0.079, 95% CI -0.142 to -0.017, P=0.013; fT4: B=-0.411, 95% CI -0.780 to -0.042, P=0.030) in euthyroid men, independent of age. FT3 level was inversely associated with intramuscular fat area (B=-0.059, 95% CI -0.106 to -0.011, P=0.016) and hepatic fat quantity (B=-0.237, 95% CI -0.441 to -0.033, P=0.024) in euthyroid men, independent of age. CONCLUSIONS In euthyroid men, low levels of fT3 and fT4 were significantly associated with increased pericardial fat volume and BMI.

A case of mediastinal ectopic thyroid presenting with a paratracheal mass.

Mediastinal ectopic thyroid is a very rare condition, with few reported cases in the literature and no reported cases in Korea. This report describes an asymptomatic 65-year-old man with a right paratracheal mass compressing the superior vena. Additionally, the epidemiology, clinical manifestation, diagnosis, and management of mediastinal ectopic thyroids are discussed. A mediastinal ectopic thyroid should be considered in the differential diagnosis of all mediastinal masses. Surgical excision is recommended for both the diagnosis and treatment of this condition, because of its potential for malignancy and compression of mediastinal structures. This case demonstrates the clinical importance of mediastinal etopic thyroid.