Jae Hee Ahn

Evening Chronotype Is Associated With Metabolic Disorders and Body Composition in Middle-Aged Adults

CONTEXT Chronotype is a trait determining individual circadian preference in behavioral and biological rhythm relative to external light-dark cycle. However, little is known about the relationship between chronotype and metabolic disorders. OBJECTIVE The aim of this study was to examine whether late chronotype is related to metabolic abnormalities and body composition in middle-aged adults, independent of sleep duration and lifestyle. DESIGN AND PARTICIPANTS A total of 1620 participants aged 47-59 years were recruited from the Korean Genome and Epidemiology Study. MAIN OUTCOME MEASURES Chronotype was assessed by the Morningness-Eveningness Questionnaire. Associations of chronotype with diabetes, metabolic syndrome, sarcopenia, and visceral obesity were analyzed. All participants underwent the oral glucose tolerance test, and body composition was measured with dual energy x-ray absorptiometry. Visceral obesity was designated as visceral fat area, measured by abdominal computed tomography, of >100 cm(2). RESULTS Chronotype was classified as morning in 29.6% of subjects, evening in 5.9%, neither morning nor evening in 64.5%. Evening type, when compared with morning type, was significantly associated with diabetes (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.01-2.95), metabolic syndrome (OR, 1.74; 95% CI, 1.05-2.87), and sarcopenia (OR, 3.16; 95% CI, 1.36-7.33) after adjusting for confounding factors. Gender differences in the associations were evident. In men, evening type was associated with diabetes (OR, 2.98; 95% CI, 1.39-6.39) and sarcopenia (OR, 3.89; 95% CI, 1.33-11.33). Only metabolic syndrome was associated with evening type in women (OR, 2.22; 95% CI, 1.11-4.43). CONCLUSIONS At the population level, evening chronotype was independently associated with diabetes, metabolic syndrome, and sarcopenia. These results support the importance of circadian rhythms in metabolic regulation.

Prevalence and Determinants of Diabetic Nephropathy in Korea: Korea National Health and Nutrition Examination Survey

Background Diabetic nephropathy is a leading cause of end stage renal disease and is associated with an increased risk of cardiovascular mortality. It manifests as albuminuria or impaired glomerular filtration rate (GFR), and the prevalence of diabetic nephropathy varies with ethnicity. The prevalence of diabetic nephropathy and its determinants in Korean adults have not previously been studied at the national level. This cross-sectional study was undertaken to ascertain the prevalence and determinants of albuminuria and chronic kidney disease (CKD) in Korean patients with diabetes. Methods The Korea National Health and Nutrition Examination Survey (KNHANES) V, conducted in 2011, was used to define albuminuria (n=4,652), and the dataset of KNHANES IV-V (2008-2011) was used to define CKD (n=21,521). Selected samples were weighted to represent the entire civilian population in Korea. Albuminuria was defined as a spot urine albumin/creatinine ratio >30 mg/g. CKD was defined as a GFR <60 mL/min/1.73 m2. Results Among subjects with diabetes, 26.7% had albuminuria, and 8.6% had CKD. Diabetes was associated with an approximate 2.5-fold increased risk of albuminuria, with virtually no difference between new-onset and previously diagnosed diabetes. Only systolic blood pressure was significantly associated with albuminuria, and old age, high serum triglyceride levels, and previous cardiovascular disease (CVD) were related with CKD in subjects with diabetes. Conclusion Korean subjects with diabetes had a higher prevalence of albuminuria and CKD than those without diabetes. Blood pressure was associated with albuminuria, and age, triglyceride level, and previous CVD were independent determinants of CKD in subjects with diabetes.

Association of Obstructive Sleep Apnea and Glucose Metabolism in Subjects With or Without Obesity

OBJECTIVE The purpose of this study was to investigate whether the impact of obstructive sleep apnea (OSA) on glucose metabolism was different according to the presence or absence of obesity. RESEARCH DESIGN AND METHODS A total of 1,344 subjects >40 years old from the Korean Genome and Epidemiology Study were included. OSA was detected by home portable sleep monitoring. Plasma glucose, HbA1c, and insulin resistance were compared according to OSA and obesity status. The associations between OSA and impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT, and diabetes were evaluated in subjects with and without obesity after adjusting for several confounding variables. The effect of visceral obesity on this association was evaluated in 820 subjects who underwent abdominal computed tomography scanning. RESULTS In subjects without obesity, fasting glucose, 2-h glucose after 75-g glucose loading, and HbA1c were higher in those with OSA than in those without after controlling for age, sex, and BMI. In addition, the presence of OSA in nonobese subjects was associated with a higher prevalence of IFG + IGT and diabetes after adjusting for several confounding variables (odds ratio 3.15 [95% CI 1.44–6.90] and 2.24 [1.43–3.50] for IFG + IGT and diabetes, respectively). Further adjustment for visceral fat area did not modify this association. In contrast, in those with obesity, none of the abnormal glucose tolerance categories were associated with OSA. CONCLUSIONS The presence of OSA in nonobese individuals is significantly associated with impaired glucose metabolism, which can be responsible for future risk for diabetes and cardiovascular disease.

Nut consumption has favorable effects on lipid profiles of Korean women with metabolic syndrome.

Nut consumption has been studied for its cardioprotective effects. However, the findings of clinical intervention studies are inconsistent; and no intervention studies have been conducted in the Korean population. We hypothesized that nut supplementation may have favorable influence on metabolic markers. Therefore, this study aimed to investigate the effects of nut consumption on metabolic parameters and biomarkers related to inflammation, oxidative stress, and endothelial function in Korean adults with metabolic syndrome. To this end, we designed a randomized, parallel, controlled dietary intervention study (ClinicalTrials.gov NCT02023749). Subjects with metabolic syndrome and a body mass index of at least 23 kg/m(2) were randomized to the Control group and the Nut group, which received supplementation with 30 g/d of mixed nuts (walnuts, peanuts, and pine nuts) for 6 weeks. Sixty volunteers were included in the final analysis. Metabolic markers were evaluated at baseline and at the end of the study. Total cholesterol and non-high-density lipoprotein cholesterol levels significantly improved in the Nut group compared to those in the Control group (P = .023 and P = .016, respectively) in women. Biomarkers related to inflammation, oxidative stress, and endothelial function did not significantly change from baseline in either group. Thus, supplementing a usual diet with mixed nuts for 6 weeks had favorable effects on several lipid parameters in Korean women with metabolic syndrome. These findings present a possible mechanism for the cardioprotective effects of nut consumption.

Effects of low‐fat milk consumption on metabolic and atherogenic biomarkers in Korean adults with the metabolic syndrome: a randomised controlled trial

BACKGROUND Previous studies of the health effects of low-fat milk or dairy consumption on the metabolic syndrome have yielded inconsistent results. The present study aimed to investigate the effects of low-fat milk consumption on traits associated with the metabolic syndrome, as well as inflammatory and atherogenic biomarkers, in Korean adults with the metabolic syndrome. METHODS Overweight Koreans with the metabolic syndrome (n = 58) were recruited and randomly assigned to either the low-fat milk or control group. The low-fat milk group was instructed to consume two packs of low-fat milk per day (200 mL twice daily) for 6 weeks, and the control group was instructed to maintain their habitual diet. Clinical investigations were conducted during the screening visit, on study day 0, and after 6 weeks. RESULTS No significant differences in changes in body mass index, blood pressure, lipid profile and adiponectin levels, as well as levels of inflammatory markers, oxidative stress markers and atherogenic markers, were found between the low-fat milk and control groups. However, compared to the controls, significant favourable decreases in serum soluble vascular adhesion molecule-1 and endothelin-1 levels were found in the 12 subjects with high blood pressure and in the 18 subjects with hypertriglyceridaemia in the low-fat milk group. CONCLUSIONS The present study did not demonstrate an overall beneficial effect of low-fat milk consumption in subjects with the metabolic syndrome. However, low-fat milk consumption may have a favourable effect on atherogenic markers in subjects with high blood pressure or hypertriglyceridaemia.

HIF‐1α Expression as a Protective Strategy of HepG2 Cells Against Fatty Acid‐Induced Toxicity

Free fatty acid‐induced lipotoxicity via increased endoplasmic reticulum (ER) stress and hepatocyte apoptosis is a key pathological mechanism of non‐alcoholic steatohepatitis. A role of hypoxia‐inducible factor 1α (HIF‐1α) in this process has been suggested, but direct evidence is lacking. Here, we used HepG2 cells as a model to study whether HIF‐1α can reduce palmitic acid‐induced lipotoxicity and ER stress. In HepG2 cells treated with 500 µM palmitic acid, HIF‐1α expression increased transiently, the decline was associated with increased cleaved caspase‐3 expression. Overexpression and knockdown of HIF‐1α decreased and exacerbated, respectively, palmitic acid‐induced lipoapoptosis. The overexpression also blunted upregulation of the ER stress markers, C/EBP homologous protein (CHOP) and chaperone immunoglobulin heavy chain binding protein (Bip), while the knockdown increased the level of CHOP. In line with this, CHOP promoter activity decreased following HIF‐1α binding to the CHOP promoter hypoxia response element. These results indicate that hepatocyte lipotoxicity is associated with decreased HIF‐1α expression. It also suggests that upregulation of HIF‐1α can be a possible strategy to reduce lipotoxicity in non‐alcoholic fatty liver disease. J. Cell. Biochem. 115: 1147–1158, 2014.

Obstructive sleep apnea with excessive daytime sleepiness is associated with non-alcoholic fatty liver disease regardless of visceral fat

Background/Aims: Obstructive sleep apnea (OSA) is associated with an increased risk of obesity and non-alcoholic fatty liver disease (NAFLD), but it remains unclear whether the risk of NAFLD is independently related to OSA regardless of visceral obesity. Thus, the aim of the present study was to examine whether OSA alone or in combination with excessive daytime sleepiness (EDS) or short sleep duration was associated with NAFLD independent of visceral fat in Korean adults. Methods: A total of 621 participants were selected from the Korean Genome and Epidemiology Study (KoGES). The abdominal visceral fat area (VFA) and hepatic fat components of the participants were assessed using computed tomography scans and they were then categorized into four groups depending on the presence of OSA and EDS. Results: The proportions of NAFLD were 21.1%, 18.5%, 32.4%, and 46.7% in participants without OSA/EDS, with only EDS, with only OSA, and with both OSA and EDS, respectively. A combination of OSA and EDS increased the odds ratio (OR) for developing NAFLD (OR, 2.75; 95% confidence interval [CI], 1.21 to 6.28) compared to those without OSA/EDS, and this association remained significant (OR, 2.38; 95% CI, 1.01 to 5.59) even after adjusting for VFA. In short sleepers (< 5 hours) with OSA, the adjusted OR for NAFLD was 2.50 (95% CI, 1.08 to 5.75) compared to those sleeping longer than 5 hours without OSA. Conclusions: In the present study, OSA was closely associated with NAFLD in Korean adults. This association was particularly strong in those with EDS or short sleep duration regardless of VFA.

Effect of eplerenone, a selective aldosterone blocker, on the development of diabetic nephropathy in type 2 diabetic rats.

Background Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats. Methods Animals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks. Results Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-β1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups. Conclusion Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug.

Changes in the clinical manifestations of primary aldosteronism

Background/Aims Primary aldosteronism (PA) is now widely recognized to have a higher prevalence than was once thought. In view of its increasing prevalence, we compared chronological changes in clinical manifestations of PA according to different times of diagnosis. Methods In total, 85 patients diagnosed with PA from January 1986 through March 2012 were reviewed retrospectively, based on their medical records. During two periods-1986 to 2005 and 2006 to 2012-41 and 44 patients, respectively, were diagnosed with PA. We compared the clinical and biological characteristics of PA between these periods. Results The results demonstrate an increasing trend in the prevalence of idiopathic hyperaldosteronism (IHA; p = 0.19). In the 2006 to 2012 period, patients with PA presented with higher serum potassium levels at the time of diagnosis than in the 1986 to 2005 period (p < 0.0002). Adrenal vein sampling (AVS) was performed mostly in the latter period (82.3%) and the diagnostic accuracy of adrenal computed tomography, compared with AVS, was only 56.2%. About 78.0% versus 86.3% of patients had at least one target organ damage (TOD) in the 1986 to 2005 and 2006 to 2012 periods, respectively (p = 0.39). However, patients with TOD were older and had longer durations of hypertension than patients without, in both periods. Conclusions PA is becoming more prevalent. There was an increasing tendency for IHA, and more PA patients presented with normokalemia than in the earlier period. Early and accurate diagnosis of PA with AVS and proper treatment should have substantial prognostic value.

Pheochromocytoma with Markedly Abnormal Liver Function Tests and Severe Leukocytosis

Pheochromocytoma is a rare neuroendocrine tumor arising from the medulla of the adrenal glands, which causes an overproduction of catecholamines. The common symptoms are headache, palpitations, and sweating; however, various other clinical manifestations might also be present. Accurate diagnosis of pheochromocytoma is important because surgical treatment is usually successful, and associated clinical problems are reversible if treated early. A 49-year-old man with a history of uncontrolled hypertension and diabetes mellitus presented with chest pain, fever, and sweating. His liver function tests and white blood cell counts were markedly increased and his echocardiography results suggested stress-induced cardiomyopathy. His abdominal computed tomography showed a 5×5-cm-sized tumor in the left adrenal gland, and laboratory tests confirmed catecholamine overproduction. After surgical resection of the left adrenal gland, his liver function tests and white blood cell counts normalized, and echocardiography showed normal cardiac function. Moreover, his previous antihypertensive regimen was deescalated, and his previously uncontrolled blood glucose levels normalized without medication.