The ratio of skeletal muscle mass to visceral fat area is a main determinant linking circulating irisin to metabolic phenotype.

BACKGROUND: The aims of this study were to investigate whether circulating irisin is associated with favorable metabolic parameters and how the association differs according to body composition in humans. METHODS: A total of 424 subjects (233 men and 191 women), aged 23-73 years (mean age 47.1 years), were enrolled from the Seoul Metro City Diabetes Prevention Program. Body composition was determined using an impedance body composition analyzer, and serum irisin level was measured using a commercial kit. RESULTS: Serum irisin was correlated with favorable metabolic parameters including less obese, lower blood pressure and glucose levels and healthy lipid parameters. The skeletal muscle mass to visceral fat area ratio (SVR) was positively correlated with the serum irisin concentration (r = 0.10, P = 0.04). When the study subjects were divided into tertiles according to their SVR, serum irisin was correlated with favorable metabolic phenotypes in those subjects in the upper tertile. However, there were no such correlations in the lower tertile. In addition, serum irisin was inversely related to pre-diabetes/type 2 diabetes (T2D) independent of other risk factor for T2D and insulin resistance [OR (95 % CI); 0.66 (0.49-0.90), P = 0.009]. CONCLUSIONS: The compositions of skeletal muscle and visceral fat play key roles in the association between circulating irisin and a patient's metabolic phenotype.

Higher association of coronary artery calcification with non-alcoholic fatty liver disease than with abdominal obesity in middle-aged Korean men: the Kangbuk Samsung Health Study.

BACKGROUND: It is uncertain whether non-alcoholic fatty liver disease (NAFLD) or abdominal obesity is more associated with atherosclerosis. The aim of this study was to determine whether NAFLD or abdominal obesity is more strongly associated with subclinical atherosclerosis represented by coronary artery calcification (CAC). METHODS: A total of 21,335 male participants in a health screening program (mean age 41 years) were enrolled. Ultrasonographic measurements of fatty liver and multi-detector computed tomography were performed to determine the coronary artery calcium score (CACS). The presence of CAC was defined as CACS > 0. Subjects were divided into four groups according to the presence or absence of NAFLD and/or abdominal obesity as assessed by waist-hip ratio (WHR) > 0.9. RESULTS: The presence of CAC was detected in 2,385 subjects (11.2%). The proportion of subjects with CAC was highest in the abdominal obesity only group (23.2%). After adjustment for age, diabetes history, hypertension, cigarette smoking, and physical inactivity, the odds ratio (OR) for CAC was the highest in the group with both abnormalities [1.465 (1.324-1.623)]. The NAFLD only group showed significantly increased OR for CAC compared to that in the abdominal obesity only group [1.286 (1.151-1.436) vs. 1.076 (0.939-1.233)]. CONCLUSION: Non-alcoholic fatty liver disease is more closely associated with CAC than abdominal obesity as assessed by the WHR. NAFLD could be considered an independent determinant of subclinical atherosclerosis as assessed by CAC.

Urinary adiponectin concentration is positively associated with micro- and macro-vascular complications.

BACKGROUND: A relationship between plasma adiponectin level and a number of metabolic conditions, including insulin resistance, obesity, and type 2 diabetes, has been reported. This study aimed to assess whether urinary adiponectin concentration is correlated with vascular complications. METHODS: The study comprised 708 subjects who enrolled in the Seoul Metro City Diabetes Prevention Program and were carefully monitored from September 2008 to December 2008. Levels of urinary adiponectin were measured using an enzyme linked immunosorbent assay (ELISA) kit (AdipoGen, Korea). Urinary albumin excretion was assessed by the ratio of urinary albumin to creatinine (A/C ratio). Participants were divided into three groups based on tertiles of urinary adiponectin concentration, and we investigated whether urinary adiponectin levels are associated with microalbuminuria and pulse wave velocity. RESULTS: Urinary adiponectin concentrations were significantly higher in subjects with microalbuminuria than subjects with normoalbuminuria (P < 0.001). Urinary adiponectin concentration was positively correlated with age, fasting plasma glucose level, HbA1C level, triglyceride level, HOMA-IR, systolic/diastolic blood pressure, and urinary A/C ratio (all P < 0.05). Subjects in the highest tertile of urinary adiponectin concentration had an increased likelihood of microalbuminuria than those in the lowest tertile (Odds ratio (OR), 6.437; 95% confidence interval (CI), 4.202 to 9.862; P < 0.001). After adjusting for age, sex, and estimated creatinine clearance rate (eCcr), the OR remained significant (OR, 5.607; 95% CI, 3.562 to 8.828; P < 0.001). Backward multiple linear regression analysis revealed urinary adiponectin concentration to be a significant determinant of mean brachial-ankle pulse wave velocity (baPWV). CONCLUSIONS: An increased urinary adiponectin concentration is significantly associated with microalbuminuria and increased mean baPWV. These results suggest that urinary adiponectin may play an important role as a biomarker for vascular dysfunction.

The association of serum glycated albumin with the prevalence of diabetic retinopathy in Korean patients with type 2 diabetes mellitus.

AIMS: To determine the clinical relationship between serum glycated albumin (GA) and diabetic retinopathy in Korean patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study including 424 patients with T2DM was conducted. Patients were divided into groups based on the presence of diabetic retinopathy and tertiles of serum GA and 1,5-anhydroglucitol levels. RESULTS: Patients in the highest tertile of GA had a higher risk of diabetic retinopathy than those in the lowest tertile. Further analysis divided the groups based on glycated hemoglobin (HbA1c) levels, either above or below 8% (64mmol/mol), and revealed that in those with a HbA1c below 8% (64mmol/mol), the higher GA subgroup had an increased presence of diabetic retinopathy. CONCLUSIONS: An increased GA level was significantly correlated with the presence of diabetic retinopathy, and measuring GA levels in addition to HbA1c was beneficial as a marker for retinopathy, especially in patients with moderate glycemic control.

Increased association of coronary artery calcification in apparently healthy Korean adults with hypertriglyceridemic waist phenotype: The Kangbuk Samsung Health Study.

BACKGROUND: Hypertriglyceridemic waist phenotype is a simple screening parameter to identify people at increased risk for cardiovascular disease. We evaluated whether hypertriglyceridemic waist (HTGW) phenotype increases the risk for coronary artery calcification (CAC) in apparently healthy Korean adults. METHODS: A total of 32,186 participants (mean age 41.3, 80.2% men) in a health screening program, in whom the coronary artery calcium score (CACS) was measured, were analyzed. Subjects were divided into four groups: 1) normal waist circumference (WC)-normal triglyceride (TG) (NWNT), 2) normal WC-high TG (NWHT), 3) enlarged WC-normal TG (EWNT), and 4) enlarged WC-high TG (EWHT). Enlarged WC was defined as WC ≥ 90 cm for men and ≥ 85 cm for women; high serum TG was defined as TG ≥ 150 mg/dL. The presence of CAC was defined by CACS >0, and CACS was analyzed in a logarithmized form of CACS plus 1 {ln(CACS+1)}. RESULTS: A total of 14.9% of the participants had CAC. The EWHT group showed the highest mean value for ln(CACS+1) among the four groups. The EWHT group showed the highest odds ratio for CAC, with NWHT group the second, and with EWNT group the third compared with the NWNT group after adjusting for confounding variables (1.579, 1.302, and 1.266 vs. NWNT). CONCLUSIONS: The EWHT group showed the highest association for CAC, suggesting this HTGW phenotype as a useful marker for the detection of subjects with high cardiometabolic risk in healthy Korean adults.

Comparison of Serum Adipocytokine Levels according to Metabolic Health and Obesity Status.

BACKGROUND: Metabolic health is an emerging concept that is highly correlated with various metabolic complications, and adipocytokines have been causally linked to a wide range of metabolic diseases. Thus, this study compared serum adipocytokine levels according to metabolic health and obesity status. METHODS: Four hundred and fifty-six nondiabetic subjects (mean age, 40.5 years) were categorized into four groups according to metabolic health and obesity status: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUHNO), and metabolically unhealthy obese (MUHO). Being metabolically healthy was defined as the presence of fewer than two of the following five metabolic abnormalities: high blood pressure, high fasting blood glucose, high triglyceride, low high density lipoprotein cholesterol, and being in the highest decile of the homeostatic model assessment of insulin resistance index. Obesity status was assessed using body mass index (BMI), with obesity defined as a BMI higher than 25 kg/m². Levels of serum interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor α (TNF-α), and adipocyte fatty acid binding protein (A-FABP) were also evaluated. RESULTS: Of the 456 subjects, 247 (54.2%) were in the MHNO group, 66 (14.5%) were in the MHO group, 66 (14.5%) were in the MUHNO group, and 77 (16.9%) were in the MUHO group. There were no significant differences in IL-6 or MCP-1 levels among the groups, but levels of TNF-α and A-FABP were significantly higher in the MUHNO group compared to the MHNO group. CONCLUSION: High TNF-α and A-FABP levels are significantly associated with metabolically unhealthiness in nonobese Korean individuals.

Antiobesity pharmacotherapy for patients with type 2 diabetes: focus on long-term management.

Type 2 diabetes and obesity have a complex relationship; obesity is linked to insulin resistance, the precursor to type 2 diabetes. The management of obesity is an important method to delay onset of diabetes and improve the glycemic durability of antidiabetic agents. However, insulin and some of the oral hypoglycemic agents used to treat diabetes cause significant weight gain, and it is difficult for patients with diabetes to reduce and maintain their weight by life-style changes alone. Thus, antiobesity medications or bariatric surgery may be a necessary adjunct for certain obese patients with diabetes. In 2012, the U.S. Food and Drug Administration (FDA) approved lorcaserin and phentermine/topiramate extended-release for the management of chronic weight, and approval for naltrexone/bupropion sustained-release as an adjunct to exercise and reduced caloric intake followed in 2014. Liraglutide is pending FDA approval for antiobesity drug. Here we review the efficacy of approved and new promising drugs for the management of obesity.

Metabolic health is a more important determinant for diabetes development than simple obesity: a 4-year retrospective longitudinal study.

BACKGROUND: Recent studies report the importance of metabolic health beyond obesity. The aim of this study is to compare the risk for diabetes development according to different status of metabolic health and obesity over a median follow-up of 48.7 months. METHODS: 6,748 non-diabetic subjects (mean age 43 years) were divided into four groups according to the baseline metabolic health and obesity status: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUHNO) and metabolically unhealthy obese (MUHO). Being metabolically healthy was defined by having less than 2 components among the 5 components, that is, high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol and being in the highest decile of homeostasis model assessment-insulin resistance (HOMA-IR) index. Obesity status was assessed by body mass index (BMI) higher than 25 kg/m2. The development of diabetes was assessed annually from self-questionnaire, fasting glucose and HbA1c. RESULTS: At baseline, 45.3% of the subjects were MHNO, 11.3% were MHO, 21.7% were MUHNO, and 21.7% were MUHO. During a median follow-up of 48.7 months, 277 subject (4.1%) developed diabetes. The hazard ratio for diabetes development was 1.338 in MHO group (95% CI 0.67-2.672), 4.321 in MUHNO group (95% CI 2.702-6.910) and 5.994 in MUHO group (95% CI 3.561-10.085) when MHNO group was considered as the reference group. These results were similar after adjustment for the changes of the risk factors during the follow-up period. CONCLUSION: The risk for future diabetes development was higher in metabolically unhealthy subgroups compared with those of metabolically healthy subjects regardless of obesity status.

Optimal glycated albumin cutoff value to diagnose diabetes in Korean adults: a retrospective study based on the oral glucose tolerance test.

INTRODUCTION: Glycated albumin (GA) reflects short-term status of glycemic control. We suggest a GA cut-off value to diagnose pre-diabetes and diabetes in Korean adults. In addition, we compared the performance of GA for the diagnosis of diabetes with that of glycated hemoglobin (A1c). MATERIALS AND METHODS: A total of 852 subjects (498 males, 354 females) aged 20 to 83years (mean: 52.5years) were enrolled. A 75-g oral glucose tolerance test (OGTT) was performed and A1c and GA were measured. RESULTS: In these enrolled subjects, 88% have glucose intolerance status (pre-diabetes or diabetes). The GA concentrations corresponding to fasting plasma glucose (FPG) of 7.0mmol/l, 2-h plasma glucose during OGTT (PPG2)≥11.1mmol/l, and A1c≥6.5% were 14.6%, 13.7%, and 14.7%, respectively. A meta-analysis of three GA cutoffs revealed a GA cutoff for diabetes of 14.3%. When A1c is used in combination with FPG, the sensitivity and specificity for the diagnosis of OGTT-based diabetes were 72.16% (95% CI: 66.6-72.2) and 96.4% (95% CI: 94.4-97.7), respectively. With the newly developed GA cutoff of 14.3%, GA combined with FPG resulted in a sensitivity and specificity of 77.5% (95% CI: 72.17-82.0) and 89.9% (95% CI: 87.1-92.2), respectively. CONCLUSIONS: A GA cutoff of >14.3% is optimal for the diagnosis of diabetes in Korean adults. The measurement of FPG and GA may detect diabetes earlier than the measurement of FPG and A1c.

Hemoglobin A1c values are affected by hemoglobin level and gender in non-anemic Koreans.

AIMS/INTRODUCTION: To evaluate whether hemoglobin A1c (HbA1c) levels are affected by hemoglobin level and gender. MATERIALS AND METHODS: A cross-sectional analysis was carried out in a sample of 87,284 non-diabetic Koreans without anemia who participated in comprehensive health check-ups between January and December 2009 at the Kangbuk Samsung Hospital Total Healthcare Center in Seoul, Korea. We categorized men and women separately according to fasting plasma glucose and hemoglobin level to carry out the analysis. RESULTS: HbA1c increased steadily with increasing fasting plasma glucose level. Both men and women with lower hemoglobin had significantly higher HbA1c at a given fasting glucose level, and this result was consistent across the fasting glucose quintiles within the non-diabetic range. Women had a lower mean hemoglobin value compared with men, and women had higher HbA1c levels at a given fasting glucose level consistently across the fasting glucose deciles. There was also a gender-specific association between age and HbA1c (P < 0.001 for interaction). CONCLUSIONS: HbA1c values were affected by hemoglobin level and gender in non-anemic Koreans. Thus, hemoglobin level and gender should be considered in the diagnosis of diabetes using HbA1c.

Development of an HbA1c-based conversion equation for estimating glycated albumin in a Korean population with a wide range of glucose intolerance.

BACKGROUND: Compared to the golden standard glycation index of HbA1c, glycated albumin (GA) has potentials for assessing insulin secretory dysfunction and glycemic fluctuation as well as predicting diabetic vascular complications. However, the reference ranges of GA and a conversion equation need to be clearly defined. We designed this study to determine the reference ranges in patients with normal glucose tolerance (NGT) based on conventional measures of glycemic status and to devise a conversion equation for calculating HbA1c and GA in a Korean population. METHODOLOGY/PRINCIPAL FINDINGS: In this multicenter, retrospective, cross-sectional study, we recruited antidiabetic drug-naïve patients with available glycemic variables including HbA1c, GA, and fasting plasma glucose regardless of glucose status. For the reference interval of serum GA, 5th to 95th percentile value of GA in subjects with NGT was adopted. The conversion equation between HbA1c and GA was devised using an estimating regression model with unknown break-points method. The reference range for GA was 9.0-14.0% in 2043 subjects. The 95th percentile responding values for FPG, and HbA1c were approximately 5.49 mmol/l, and 5.6%, respectively. The significant glycemic turning points were 5.868% HbA1c and 12.2% GA. The proposed conversion equation for below and above the turning point were GA (%) = 6.960+0.8963 × HbA1c (%) and GA (%) = -9.609+3.720 × HbA1c (%), respectively. CONCLUSIONS/SIGNIFICANCE: These results should be helpful in future studies on the clinical implications of high GA relative to HbA1c and the clinical implementation of diabetes management.

Increased risk of diabetes development in subjects with the hypertriglyceridemic waist phenotype: a 4-year longitudinal study.

BACKGROUND: The hypertriglyceridemic waist (HTGW) phenotype is a simple and inexpensive screening parameter to identify people at increased risk of cardiovascular disease. We evaluated whether the HTGW phenotype predicts diabetes in urban Korean adults. METHODS: A total of 2,900 nondiabetic subjects (mean age 44.3 years), comprising 2,078 males (71.7%) and 822 females (28.3%) who underwent annual medical check-ups at our center between January 2005 and December 2009, were recruited. The subjects were divided into four groups according to baseline serum triglyceride (TG) level and waist circumference (WC): normal WC-normal TG (NWNT) level, normal WC-high TG level, enlarged WC-normal TG level, and enlarged WC-high TG (EWHT) level. High serum TG level was defined as ≥150 mg/dL and enlarged WC was defined as ≥90 cm for men and ≥85 cm for women. New cases of diabetes were determined according to questionnaires filled in by participants and the diagnostic criteria of the American Diabetes Association. Cox proportional hazards model analysis was used to assess the association of HTGW phenotype with the incidence of diabetes. RESULTS: A total of 101 (3.5%) new diabetes cases were diagnosed during the study period. The EWHT group had a higher incidence of diabetes (8.3%) compared with the NWNT group (2.2%). The adjusted hazard ratio for diabetes for subjects with the EWHT phenotype at baseline was 4.113 (95% confidence interval [CI], 2.397 to 7.059) after adjustment for age, and 2.429 (95% CI, 1.370 to 4.307) after adjustment for age, sex, total cholesterol, systolic blood pressure, and alcohol drinking history. It was attenuated by inclusion of baseline fasting glucose level in the model. CONCLUSION: Subjects with the HTGW phenotype showed the highest risk of incident diabetes. This tool could be useful for identifying individuals at high risk of diabetes.

Age Is the Strongest Effector for the Relationship between Estimated Glomerular Filtration Rate and Coronary Artery Calcification in Apparently Healthy Korean Adults.

BACKGROUND: Chronic kidney disease (CKD) is considered one of the most common risk factors for cardiovascular disease. Coronary artery calcification (CAC) is a potential mechanism that explains the association between renal function and cardiovascular mortality. We aimed to evaluate the association between renal function and CAC in apparently healthy Korean subjects. METHODS: A total of 23,617 participants in a health-screening program at Kangbuk Samsung Hospital were included in the study. Estimated glomerular filtration rate (eGFR) was assessed using the Cockcroft-Gault equation. Coronary artery calcium score (CACS) was measured via multidetector computed tomography. Subjects were divided into three groups according to the CKD Staging system with eGFR grade: stage 1, eGFR ≥90 mL/min/1.73 m(2); stage 2, eGFR 60 to 89 mL/min/1.73 m(2); and stage 3, eGFR 30 to 59 mL/min/1.73 m(2). RESULTS: The mean age of the participants was 41.4 years and the mean eGFR was 103.6±21.7 mL/min/1.73 m(2). Hypertension and diabetes were noted in 43.7% and 5.5% of the participants, respectively. eGFR showed a weakly negative but significant association with CACS in bivariate correlation analysis (r=-0.076, P<0.01). Mean CACS significantly increased from CKD stage 1 to 3. The proportion of subjects who had CAC significantly increased from CKD stage 1 to 3. Although the odds ratio for CAC significantly increased from stage 1 to 3 after adjustment for confounding factors, this significance was reversed when age was included in the model. CONCLUSION: In early CKD, renal function negatively correlated with the degree of CAC in Korean subjects. Age was the strongest effector for this association.

Association of serum adipocyte-specific Fatty Acid binding protein with Fatty liver index as a predictive indicator of nonalcoholic Fatty liver disease.

BACKGROUND: Adipocyte-specific fatty acid-binding protein (A-FABP) is a cytoplasmic protein expressed in macrophages and adipocytes and it plays a role in insulin resistance and metabolic syndrome. Recently, the fatty liver index (FLI) was introduced as an indicator of nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the relationship between baseline serum A-FABP levels and FLI after 4 years in apparently healthy subjects. METHODS: A total of 238 subjects without a past history of alcoholism or hepatitis were recruited from a medical check-up program. The NAFLD state was evaluated 4 years later in the same subjects using FLI. Fatty liver disease was diagnosed as diffusely increased echogenicity of the hepatic parenchyma compared to the kidneys, vascular blurring, and deep-echo attenuation. NAFLD was defined as subjects with fatty liver and no history of alcohol consumption (>20 g/day). RESULTS: Baseline serum A-FABP levels were significantly associated with FLI after adjustment for age and sex (P<0.001). The subjects with higher A-FABP levels had a higher mean FLI (P for trend=0.006). After adjusting for age and sex, serum A-FABP levels at baseline were shown to be significantly associated with FLI as a marker of development of NAFLD after 4 years (odds ratio, 2.68; 95% confidence interval, 1.24 to 5.80 for highest tertile vs. lowest tertile; P=0.012). CONCLUSION: This study demonstrated that higher baseline serum A-FABP levels were associated with FLI as a predictive indicator of NAFLD after 4 years of follow-up in healthy Korean adults.

Metabolic health is more closely associated with coronary artery calcification than obesity.

BACKGROUND: Recent studies have suggested that metabolic health may contribute more to the atherosclerosis than obesity. The aim of this study is to compare coronary artery calcium scores (CACS) among patients with different metabolic health and obesity status. METHODS: A health-screening program of 24,063 participants (mean age 41 years) was conducted, and CACS was assessed by multi-detector computerized tomography (MDCT). Being metabolically healthy was defined as having fewer than two of the following risk factors: high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol, highest decile of homeostasis model assessment-insulin resistance (HOMA-IR) index, and highest decile of high-sensitivity C-reactive protein (hs-CRP). Obesity status was defined as body mass index (BMI) higher than 25 kg/m(2). Analyses were performed in four groups divided according to metabolic health and obesity: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUHNO), and metabolically unhealthy obese (MUHO). RESULTS: Mean values of CACS in the four groups were significantly different, except those between MHNO and MHO and between MUHNO and MUHO. When multinomial logistic regression analysis was performed with five CACS categories as the dependent variables and after adjusting for age, sex, and smoking status, the MHO, MUHNO, and MUHO groups showed significantly increased odds ratio for increasing CACS categories compared with no calcification status (5.221 for CACS >400 in MUHO group with 95% CI 2.856∼5.032 with MHNO group as the reference). When other variables including the metabolic parameters were included in the same model, the risks were attenuated. CONCLUSION: Metabolic health is more closely associated with subclinical atherosclerosis than obesity as assessed by CACS.

The relationship of body composition and coronary artery calcification in apparently healthy korean adults.

BACKGROUND: We investigated the association of coronary artery calcium score (CACS) with body composition and insulin resistance in apparently healthy Korean adults. METHODS: Nine hundred forty-five participants (mean age, 48.9 years; 628 men) in a medical check-up program were selected for analysis. Body composition was assessed by bioelectrical impedance analysis (BIA). Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). The CACS was assessed by multidetector computed tomography. RESULTS: One hundred forty-six subjects (15.4%) showed coronary artery calcification and 148 subjects (15.7%) had metabolic syndrome. CACS showed a significant positive correlation with age, fasting glucose level, waist circumference (WC), blood pressure, hemoglobin A1c, HOMA-IR, and waist-hip ratio (WHR) assessed by BIA. CACS had a negative correlation with high density lipoprotein cholesterol (HDL-C). Subjects with high CACS showed significantly higher mean WHRs and lower mean values for lean body mass compared with subjects without coronary artery calcification. In logistic regression analyses with coronary artery calcification as the dependent variable, the highest quartile of WHR showed a 3.125-fold increased odds ratio for coronary artery calcification compared with the lowest quartile after adjustment for confounding variables. When receiver operating characteristics analyses were performed with coronary artery calcification as the result variable, WHR showed the largest area under the curve (AUC) value among other variables except for age and WC in women (AUC=0.696 for WHR, 0.790 for age, and 0.719 for WC in women). CONCLUSION: In our study population of apparently healthy Korean adults, WHR was the most significant predictor for coronary artery calcification among other confounding factors, suggesting that it may have implication as a marker for early atherosclerosis.

The association of baseline adipocytokine levels with glycemic progression in nondiabetic Korean adults in 4 years of follow-up.

AIMS: Low-grade inflammation and lipotoxicity contribute to insulin resistance and islet secretory dysfunction that lead to insulin deficiency. We analyzed the associations of several adipocytokines measured at baseline with glycemic progression in non-diabetic Korean subjects after a 4-year follow-up. METHODS: In 479 non-diabetic Korean subjects who underwent medical screening in 2003, serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, retinol-binding protein (RBP)-4, monocyte chemoattractant protein (MCP)-1, visfatin and fatty acid-binding protein (FABP)-4 were measured at baseline. After 4 years, changes in glycemia were assessed. RESULTS: Among the subjects, 79.2% maintained their baseline glycemic status, 14.6% progressed to worse glycemic status (impaired fasting glucose (IFG) to diabetes, normoglycemia to IFG or normoglycemia to diabetes) and 5.8% regressed to normoglycemia after 4 years. Baseline TNF-α and FABP4 showed the highest values in the progression group. In the logistic regression analyses with glycemic progression as the dependent variable and TNF-α and FABP4 as independent variables in separate models, TNF-α and FABP4 individually predicted glycemic progression after adjustment for confounding variables. When both adipocytokines were included in the same model, only FABP4 significantly predicted glycemic progression after 4 years. CONCLUSIONS: TNF-α and FABP4 were significant predictors for glycemic progression in 4 years, with FABP4 being the stronger predictor.