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Background: Little research has been done to examine whether γ-glutamyltransferase (GGT) is prospectively associated with the development of chronic kidney disease (CKD). We performed a prospective study to examine the association between GGT and the risk for the development of CKD. Methods: The study cohort included a total of 10 337 healthy males with normal baseline kidney functions and no proteinuria. Participants were workers in a semiconductor manufacturing company and its 13 affiliates. CKD was defined as either the presence of proteinuria or a glomerular filtration rate (GFR) of <60 mL · min−1 · (1.732)−1. Cox proportional hazards models were used to calculate the adjusted hazard ratios in separate models for CKD. Results: During a follow-up period of 25 774.4 person-years, 366 men developed CKD. After adjustments were made for age, baseline GFR, triglyceride, and HDL-C, the risk for CKD increased with an increasing quartile of serum GGT (p for trend <0.001). The top one fourth of serum GGT vs the bottom one fourth of relative risks for CKD was 1.90 (95% confidence interval, 1.37–2.63). These associations were also apparent in participants who consumed ≤20 g/day of alcohol and those with normal weight, with values of alanine aminotransferase within reference intervals, or with C-reactive protein <3.0 mg/L, and participants without metabolic syndrome. Conclusions: Our findings, which were obtained from a large work-site cohort and excluded individuals with diabetes and hypertension, indicated that serum GGT may be an early predictor for the development of CKD, independent of baseline confounding factors.

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OBJECTIVES: Although the existence of metabolically healthy obese (MHO) individuals has been recognized, little is known regarding metabolic health status in these subjects over time. Thus, we evaluated longitudinal changes in metabolic parameters among MHO subjects compared with metabolically healthy, normal-weight (MHNW) subjects. METHODS: A cohort study was performed on 2599 Korean men, 30 --59 years of age, with no evidence of fatty liver disease on ultrasound and no traits of metabolic syndrome at baseline. BMI was categorized based on criteria for Asian population. Study participants were followed annually or biennially between 2002 and 2009. At each visit, the fatty liver on ultrasound was assessed and metabolic abnormalities were measured. Parametric Cox models and a pooled logistic regression models were used to evaluate the relationships of BMI with incident metabolic abnormalities. RESULTS: During 9647.1 person-years of follow-up, 1673 participants developed metabolic abnormalities. After adjusting for age, smoking, alcohol intake and exercise, higher baseline BMI categories predicted increased incidences of metabolic abnormalities in a dose-response manner. The hazard ratios (95% confidence intervals) for hypertriglyceridemia, prediabetes, pre-hypertension, low high-density lipoprotein-cholesterol, fatty liver, elevated high sensitivity-C reactive protein, elevated homeostasis model assessment of insulin resistance, any metabolic abnormality and metabolic syndrome among the MHO subjects compared with the MHNW subjects were 1.51 (1. Keywords: body mass index; risk factors; insulin resistance; metabolic syndrome X; follow-up studies INTRODUCTIONObesity is a risk factor for cardiometabolic disorders such as type 2 diabetes mellitus and cardiovascular disease. 1,2 However, the incidence of obesity-related metabolic disturbances varies widely among obese individuals. 3,4 A unique subset of obese individuals that appears to be protected from obesity-related metabolic abnormalities has been identified. 3,5 These individuals, referred to as metabolically healthy but obese (MHO), are relatively insulin sensitive and have a favorable cardiovascular risk profile despite excessive body fat. 6 Previous studies indicate that MHO individuals, regardless of body mass index, are not at increased risk for cardiovascular diseases compared with normal-weight subjects without insulin resistance. 7,8 Therefore, weight loss may not be deemed necessary among these individuals.Recent longitudinal studies have observed that obese men without metabolic syndrome were at an increased risk for cardiovascular events or death compared with normal-weight individuals without metabolic syndrome. 9,10 Other studies observed that the MHO subset had an intermediate cardiovascular risk between healthy non-obese subjects and insulin resistant subjects. 11,12 Furthermore, recent intervention studies showed that lifestyle-induced weight loss among MHO individuals was associated with improved insulin sensitivity. 13,14

Several recent prospective studies have reported that obesity is associated with an increased risk for chronic kidney disease (CKD), but it is unknown whether weight gain increases the risk for CKD if one remains within the "normal" category of body mass index (BMI). We prospectively followed a cohort of 8792 healthy men who had no known risk factors for CKD and participated in a comprehensive health evaluation program at a large worksite. During 35,927 person-years of follow-up, 427 new incident cases of CKD (estimated GFR Ͻ64 ml/min per 1.73 m 2 ) developed. Cox proportional hazards modeling revealed that in both the normal-weight and overweight groups, a U-shaped association between weight change categories and development of CKD was observed after adjustment for age, baseline GFR, baseline BMI, HDL, fasting blood glucose, uric acid, and exercise habits. The lowest risk for CKD was observed among those whose weight changed Ϫ0.25 to Ͻ0.25 kg/yr (P Ͻ 0.001 for quadratic term). Weight change as a time-dependent variable was significantly related to CKD incidence. These relationships remained significant even after further adjustment for Homeostasis Model Assessment of Insulin Resistance, high-sensitivity C-reactive protein, systolic BP, diastolic BP, metabolic syndrome, incident hypertension, or incident diabetes. In summary, increases in body weight are independently associated with an increased risk for CKD, even when the BMI remains within the normal range.

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Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) are often found to coexist but the sequential relationship of NAFLD and GD to each other remains controversial. We prospectively evaluated the bidirectional relationship of NAFLD with GD. A cohort study was performed on Korean adults who underwent a health checkup and were followed annually or biennially for a mean of 6.0 years. Fatty liver and gallstones were diagnosed by ultrasound. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or other identifiable causes. The NAFLD severity was determined by non-invasive fibrosis markers. Among 283,446 participants without either gallstones or cholecystectomy at baseline, 6440 participants developed gallstones. Among 219,641 participants without NAFLD at baseline, 49,301 participants developed NAFLD. The multivariable-adjusted hazard ratio (95% confidence interval) for incident gallstone comparing the NAFLD group vs. the non-NAFLD group was 1.26 (1.17–1.35). Increased non-invasive fibrosis markers of NAFLD were positively associated with an increased incidence of gallstones in a graded and dose-responsive manner (p-trend < 0.01). The multivariable-adjusted hazard ratios (95% confidence intervals) for incident NAFLD comparing gallstone and cholecystectomy to no GD were 1.14 (1.07–1.22) and 1.17 (1.03–1.33), respectively. This large-scale cohort study of young and middle-aged individuals demonstrated a bidirectional association between NAFLD and GD. NAFLD and its severity were independently associated with an increased incidence of gallstones, while GD and cholecystectomy were also associated with incident NAFLD. Our findings indicate that the conditions may affect each other, requiring further studies to elucidate the potential mechanisms underlying this association.