Jae Hyeon Kim

Insulin-sensitizing effects of exercise on adiponectin and retinol-binding protein-4 concentrations in young and middle-aged women

CONTEXT Exercise training enhances insulin sensitivity. Changes in retinol-binding protein-4 (RBP4) and adiponectin levels are linked to insulin resistance. OBJECTIVE We tested whether the insulin-sensitizing effect of exercise is associated with age-related changes in circulating RBP4 and adiponectin levels in women. DESIGN, SUBJECTS, AND INTERVENTION We studied 36 healthy young (22.4 +/- 2.8 yr) and 38 middle-aged (59.8 +/- 5.9 yr) women. All subjects performed 60 min of aerobic exercise three times per week for 10 wk at about 70% maximal exercise capacity. RESULTS After a 10-wk training program, maximal exercise capacity was significantly increased in both young and middle-aged women, suggesting increased oxidative capacity. Insulin sensitivity was also improved, as indicated by decreases in plasma insulin levels and homeostasis model assessment for insulin resistance index. Serum adiponectin and RBP4 concentrations were increased and decreased more in older than younger women, respectively (P < 0.01). Concurrently, circulating transthyretin levels were also decreased in older subjects in response to exercise training. The older women showed higher correlations between changes in adiponectin or RBP4 levels and obesity indices or metabolic parameters than the younger group. When subjects showing increasing adiponectin or decreasing RBP4 levels were classified as responders, there were higher correlations between these changes in responders than in nonresponders. CONCLUSIONS We conclude that the mechanism for the insulin-sensitizing effects of exercise could involve increased adiponectin and reduced RBP4 levels in exercise-trained women. These data suggest that alterations in circulating RBP4 and adiponectin levels could play an important role in regulating insulin sensitivity.

Prevalence, awareness, and management of obesity in Korea: data from the Korea national health and nutrition examination survey (1998-2011).

Background Obesity is a risk factor for diabetes and several cardiovascular diseases. This study was to investigate the trends in the prevalence, awareness, and management status of obesity among the Korean population for recent 13 years. Methods The prevalence, subjective awareness, and management of obesity were investigated in adults aged ≥19 years by using the data from the Korea National Health and Nutrition Examination Surveys (KNHANES) 1998 to 2011. Results The number of participants was 8,117, 5,826, 5,500, 3,025, 6,756, 7,506, 6,255, and 6,155 in the KNHANES in years 1998, 2001, 2005, 2007, 2008, 2009, 2010, and 2011, respectively. The prevalence of obesity was 26.9%, 29.2%, 32.9%, 32.5%, 32.0%, 32.6%, 32.0%, and 32.0% in 1998, 2001, 2005, 2007, 2008, 2009, 2010, and 2011, respectively, while the overall prevalence of obesity and abdominal obesity increased by 1.19-fold and 1.24-fold respectively in 2011 compared against 2001. In general, a gradual increase in the prevalence of severe obesity has been observed as years go by. Furthermore, trends of improvements in obesity awareness and management rates were visible over the period of surveys. Conclusion Although the management status of obesity has improved during the recent years, more effective strategy to control obesity is needed.

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

Background Due to the inconvenience of performing oral glucose tolerance tests and day to day variability in glucose level, glycated hemoglobin (HbA1c) has been recommended by the American Diabetes Association as a method to diagnose diabetes. In addition, the Korean Diabetes Association has also recommended the use of HbA1c as a diagnostic test for diabetes. In this study, we evaluated the prevalence of diabetes according to fasting plasma glucose (FPG) level only or the combination of FPG and HbA1c tests. Methods Data from the 2011 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed. Among 5,811 subjects aged 30 years or older, 5,020 were selected after excluding the data of fasting time <8 hours, missing values from fasting glucose or HbA1c level, previous diagnosis of diabetes made by physicians, or current use of antidiabetic medications. Diabetes was defined as FPG ≥126 mg/dL, previous diagnosis of diabetes made by a medical doctor, current use of antidiabetic medications, and/or HbA1c ≥6.5%. Prediabetes was defined as FPG of 100 to 125 mg/dL and/or HbA1c of 5.7% to 6.4%. Results When we used FPG only, the prevalence of diabetes and prediabetes were 10.5% (men, 12.6%; women, 8.5%) and 19.3% (men, 23.8%; women, 14.9%), respectively. When HbA1c was included as a diagnostic test, the prevalence of diabetes and prediabetes increased to 12.4% (men, 14.5%; women, 10.4%) and 38.3% (men, 41%; women, 35.7%), respectively. Participants with HbA1c ≥6.5% and fasting glucose level <126 mg/dL were older and had lower estimated glomerular filtration rate. Conclusion We concluded that using fasting glucose level only may result in an underestimation of diabetes and prediabetes. HbA1c is an acceptable complementary diagnostic test for diabetes in Korean patients. However, national standardization is needed to order to use HbA1c as a diagnostic method of diabetes and prediabetes.

Amyloidogenic peptide oligomer accumulation in autophagy-deficient β cells induces diabetes

Islet amyloid accumulation is a hallmark of human type 2 diabetes (T2D). In contrast to human islet amyloid polypeptide (hIAPP), murine islet amyloid polypeptide (mIAPP) does not exhibit amyloidogenic propensity. Because autophagy is important in the clearance of amyloid-like proteins, we studied transgenic mice with β cell-specific expression of hIAPP to evaluate the contribution of autophagy in T2D-associated accumulation of hIAPP. In mice with β cell-specific expression of hIAPP, a deficiency in autophagy resulted in development of overt diabetes, which was not observed in mice expressing hIAPP alone or lacking autophagy alone. Furthermore, lack of autophagy in hIAPP-expressing animals resulted in hIAPP oligomer and amyloid accumulation in pancreatic islets, leading to increased death and decreased mass of β cells. Expression of hIAPP in purified monkey islet cells or a murine β cell line resulted in pro-hIAPP dimer formation, while dimer formation was absent or reduced dramatically in cells expressing either nonamyloidogenic mIAPP or nonfibrillar mutant hIAPP. In autophagy-deficient cells, accumulation of pro-hIAPP dimers increased markedly, and pro-hIAPP trimers were detected in the detergent-insoluble fraction. Enhancement of autophagy improved the metabolic profile of hIAPP-expressing mice fed a high-fat diet. These results suggest that autophagy promotes clearance of amyloidogenic hIAPP, autophagy deficiency exacerbates pathogenesis of human T2D, and autophagy enhancers have therapeutic potential for islet amyloid accumulation-associated human T2D.

Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs

Abstract:  Background:  Porcine pancreas is a potential source of material for islet xenotransplantation. However, the difficulty in isolating islets, because of their fragility and the variability of isolation outcome in donor age and breed, represents a major obstacle to porcine islet xenotransplantation. In this study, we compared the islet isolation yield of specific pathogen‐free (SPF) Chicago Medical School (CMS) miniature pigs with that of another miniature pig breed and market pigs from a local slaughterhouse.

Regular Exercise Is Associated with a Reduction in the Risk of NAFLD and Decreased Liver Enzymes in Individuals with NAFLD Independent of Obesity in Korean Adults

Background We evaluated the association of regular physical exercise with the presence of non-alcoholic fatty liver disease (NAFLD) and liver enzymes in relation to obesity and insulin resistance. Methodology/Principal Findings A cross-sectional analysis was conducted in 72,359 healthy Korean adults without diabetes who participated in a comprehensive health check-up. Subjects who have been exercising regularly (more than 3 times per week, at least for 30 minutes each time and for consecutive 3 month) were categorized into exercise group. All subjects were categorized into deciles based on their body mass index (BMI) and we estimated the odds ratios (ORs) for having NAFLD according to exercise regularity in each decile. The diagnosis of NAFLD was based on ultrasonography findings. Individuals with NAFLD (n = 19,921) were analyzed separately to evaluate ORs for having elevated liver enzymes based on regularity of exercise. The risk for NAFLD was significantly reduced in exercise group with age- and sex-adjusted ORs of 0.53–0.72 for all BMI deciles except at BMI categories of <19.6 and 20.7–21.6 kg/m2. While no difference was seen in BMI between subjects in exercise and non-exercise group across the BMI deciles, the values of body fat percentage and metabolic risk factors differed. Among NAFLD patients, subjects in exercise group had a lower risk for having elevated liver enzymes with multivariable adjusted OR of 0.85 (95% CI 0.74–0.99, for AST) and 0.74 (95% CI 0.67–0.81, for ALT) than did subjects in non-exercise group. Conclusions/Significance Regular exercise was associated with a reduced risk for having NAFLD and decreased liver enzymes in patients with NAFLD, and this relationship was also independent of obesity.

Glycemic Variability: How Do We Measure It and Why Is It Important?

Chronic hyperglycemia is the primary risk factor for the development of complications in diabetes mellitus (DM); however, it is believed that frequent or large glucose fluctuations may independently contribute to diabetes-related complications. Postprandial spikes in blood glucose, as well as hypoglycemic events, are blamed for increased cardiovascular events in DM. Glycemic variability (GV) includes both of these events; hence, minimizing GV can prevent future cardiovascular events. Correcting GV emerges as a target to be pursued in clinical practice to safely reduce the mean blood glucose and to determine its direct effects on vascular complications in diabetes. Modern diabetes management modalities, including glucagon-related peptide-1-based therapy, newer insulins, modern insulin pumps and bariatric surgery, significantly reduce GV. However, defining GV remains a challenge primarily due to the difficulty of measuring it and the lack of consensus regarding the optimal approach for its management. The purpose of this manuscript was not only to review the most recent evidence on GV but also to help readers better understand the available measurement options and how the various definitions relate differently to the development of diabetic complications.

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

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.

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.

Current Status of Glycemic Control of Patients with Diabetes in Korea: The Fifth Korea National Health and Nutrition Examination Survey

Background The Korea National Health and Nutrition Examination Survey (KNHANES) III (2005) reported that 22.9% of individuals with diabetes have a glycated hemoglobin (HbA1c) <6.5% and that 43.5% have an HbA1c <7%. We investigated the levels of glycemic control and the factors associated with glycemic control using data from the KNHANES V (2010 to 2012). Methods Subjects with diabetes diagnosed by a physician or those taking antidiabetic medications were classified as individuals with known diabetes. Of 1,498 subjects aged ≥30 years with diabetes, we excluded 157 individuals who were missing HbA1c data. A total of 1,341 subjects were included in the final analysis. Results The prevalence of known diabetes was 7.7% (n=1,498, estimated to be 2.32 million people). The proportions of well-controlled diabetes meeting a HbA1c goal of <6.5% and <7% were 27% and 45.6%, respectively. HbA1c increased as the duration of diabetes increased. HbA1c in subjects with a duration of diabetes ≤5 years was lower than in subjects with a duration >5 years. HbA1c in the group taking only oral hypoglycemic agents (OHAs) was significantly lower than that in the group administered only insulin or OHA and insulin in combination. In logistic regression analysis, a longer duration of diabetes, insulin use and the absence of chronic renal failure were associated with HbA1c levels >6.5%. Conclusion The level of adequate glycemic control was similar to but slightly improved compared with previous levels. The glycemic control of long-standing diabetes patients is more difficult even though they receive insulin treatment.