Body Mass Index and Mortality in the General Population and in Subjects with Chronic Disease in Korea: A Nationwide Cohort Study (2002-2010)

<div><p>Background</p><p>The association between body mass index (BMI) and mortality is not conclusive, especially in East Asian populations. Furthermore, the association has been neither supported by recent data, nor assessed after controlling for weight changes.</p><p>Methods</p><p>We evaluated the relationship between BMI and all-cause or cause-specific mortality, using prospective cohort data by the National Health Insurance Service in Korea, which consisted of more than one million subjects. A total of 153,484 Korean adults over 30 years of age without pre-existing cardiovascular disease or cancer at baseline were followed-up until 2010 (mean follow-up period = 7.91 ± 0.59 years). Study subjects repeatedly measured body weight 3.99 times, on average.</p><p>Results</p><p>During follow-up, 3,937 total deaths occurred; 557 deaths from cardiovascular disease, and 1,224 from cancer. In multiple-adjusted analyses, U-shaped associations were found between BMI and mortality from any cause, cardiovascular disease, and cancer after adjustment for age, sex, smoking status, alcohol consumption, physical activity, socioeconomic status, and weight change. Subjects with a BMI < 23 kg/m² and ≥ 30 kg/m² had higher risks of all-cause and cause-specific mortality compared with the reference group (BMI 23–24.9 kg/m²). The lowest risk of all-cause mortality was observed in subjects with a BMI of 25–26.4 kg/m² (adjusted hazard ratio [HR] 0.86; 95% CI 0.77 to 0.97). In subgroup analyses, including the elderly and those with chronic diseases (diabetes mellitus, hypertension, and chronic kidney disease), subjects with a BMI of 25–29.9 kg/m² (moderate obesity) had a lower risk of mortality compared with the reference. However, this association has been attenuated in younger individuals, in those with higher socioeconomic status, and those without chronic diseases.</p><p>Conclusion</p><p>Moderate obesity was associated more strongly with a lower risk of mortality than with normal, underweight, and overweight groups in the general population of South Korea. This obesity paradox was prominent in not only the elderly but also individuals with chronic disease.</p></div

Baseline Characteristics of the Study Subjects.

<p>Data are expressed as mean ± standard deviation or median (inter-quartile range).</p><p><i>P</i>-values were calculated by an independent two-sample <i>t</i>-test, Mann–Whitney U-test, or Pearson’s chi-square test.</p><p>AST, aspartate aminotransferase; ALT, alanine aminotransferase; HDL, high-density lipoprotein; LDL, low-density lipoprotein;HOMA-IR, homeostasis model assessment of insulin resistance; eGFR, estimated glomerular filtration rate;IL-6, interleukin-6; hsCRP, high-sensitivity C-reactive protein;CTRP-3, C1q/TNF-related protein-3; IMT, intima-media thickness.</p>*<p>Non-normally distributed.</p

Serum C1q/TNF-related Protein-3 (CTRP3) (A) and Progranulin Levels (B) According to Number of Metabolic Syndrome Components.

<p>Serum C1q/TNF-related Protein-3 (CTRP3) (A) and Progranulin Levels (B) According to Number of Metabolic Syndrome Components.</p

Spearman Correlation of Serum Progranulin and CTRP3 with Various Metabolic Parameters.

<p>CTRP-3, C1q/TNF-related protein-3; AST, aspartate aminotransferase; ALT, alanine aminotransferase; HDL, high-density lipoprotein; LDL, low-density lipoprotein;HOMA-IR, homeostasis model assessment of insulin resistance; eGFR, estimated glomerular filtration rate;IL-6, interleukin-6; hsCRP, high-sensitivity C-reactive protein;IMT, intima-media thickness.</p

Baseline characteristics according to body mass index category.

<p>Data are presented by mean ± standard deviation (SD) or %.</p><p>Baseline characteristics according to body mass index category.</p

Association between body mass index category and all-cause mortality.

<p>In the multivariable adjusted model, data was adjusted for age, sex, smoking status, alcohol intake, physical activity, socioeconomic status, and body weight change. In the analyses of stratified subgroups, the variable used in stratification was excluded.</p><p>Association between body mass index category and all-cause mortality.</p

Association of leukocyte cell-derived chemotaxin 2 (LECT2) with NAFLD, metabolic syndrome, and atherosclerosis

<div><p>Objective</p><p>Previous studies have shown that leukocyte cell-derived chemotaxin 2 (LECT2), a recently discovered hepatokine, is associated with the inflammatory response and insulin resistance. We examined circulating plasma LECT2 levels in the subjects with non-alcoholic fatty liver disease (NAFLD) or metabolic syndrome.</p><p>Methods</p><p>We analyzed plasma LECT2 levels from the subjects of age- and sex-matched 320 adults with or without NAFLD who completed a health check-up at the Health Promotion Center of Korea University Guro Hospital.</p><p>Results</p><p>Individuals with NAFLD showed significantly higher LECT2 levels (31.2 [20.9, 41.5] vs. 24.5[16.3, 32.7] ng/ml, <i>P</i> <0.001) as well as components of MetS compared to those without NAFLD. Furthermore, circulating LECT2 concentrations were greater in subjects with MetS (32.6 [17.8, 45.0] vs. 27.0 [18.7, 33.7] ng/ml, <i>P</i> = 0.016) and were associated with anthropometric measures of obesity, lipid profiles, high sensitivity C-reactive protein (hsCRP) and liver aminotransferase levels. However, there was no significant relationship between LECT2 levels and indicators of subclinical atherosclerosis, such as carotid intima-media thickness (CIMT) and brachial ankle pulse wave velocity (baPWV). Multivariate analysis demonstrated a progressively increasing trend of odds ratios for NAFLD according to quartiles of LECT2 levels after adjusting for risk factors, although the relationship was attenuated after further adjustment for waist circumference and lipid levels.</p><p>Conclusion</p><p>Circulating LECT2 concentrations were increased in individuals with NAFLD and those with MetS, but not in those with atherosclerosis. The relationship between LECT2 and both NAFLD and MetS might be mediated by its association with abdominal obesity and lipid metabolism.</p><p>Trial registration</p><p>Clinicaltrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01594710" target="_blank">NCT01594710</a></p></div

Association between body mass index and all-cause mortality according to disease status.

<p>The association between body mass index (BMI) and mortality was presented separately by those presenting with and without prevalent diabetes mellitus (DM) (A), hypertension (HTN) (B), and chronic kidney disease (CKD) (C). All analyses were adjusted for age, sex, smoking status, alcohol intake, physical activity, socioeconomic status, and body weight change.</p

Progranulin (PGRN) induced activation of the Akt/eNOS/NO pathway in HUVECs.

<p>(A) Cells were incubated with 200 ng/mL of progranulin for 0, 5, 15, 30, or 60 min and analyzed by Western blotting for phosphorylated-eNOS (p-eNOS) level. (B) HUVECs were stimulated with 200 ng/mL of progranulin with or without Akt inhibitor (0.5 or 5 µM) for 15 min, and p-eNOS level was measured by Western blotting. (C) Cells were incubated with 200 ng/mL of progranulin for the indicated times. NO production was analyzed from culture media using the Griess reagent, and OD values were measured at 540nm. Data were obtained from three separate experiments. Error bars represent mean ±SD (n.s.: not significant; *, <i>P</i>< 0.05, **, <i>P</i>< 0.005, <i>t</i>-test)..</p

Odds ratios for NAFLD according to circulating LECT2 quartiles.

<p>Odds ratios for NAFLD according to circulating LECT2 quartiles.</p