The Serum Level of KL-6 Is Associated with the Risk of Insulin Resistance and New-onset Diabetes Mellitus: The Tanno-Sobetsu Study

• Published in: Internal Medicine Vol. 56; no. 22; pp. 3009 - 3018
• Main Authors: Akasaka, Hiroshi, Ohnishi, Hirofumi, Narita, Yoshifumi, Kameda, Masami, Miki, Takayuki, Takahashi, Hiroki, Yamamoto, Wari, Sohma, Hitoshi, Masumori, Naoya, Miura, Tetsuji, investigators, SPRUCE project
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Internal Medicine 01.01.2017; Japan Science and Technology Agency
• Subjects: Bioindicators; Blood pressure; Body mass; Body mass index; Brain natriuretic peptide; Chronic obstructive pulmonary disease; Cytokines; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Health risks; Homeostasis; Independent variables; Inflammation; Infrared radiation; Insulin; Insulin resistance; Internal medicine; KL-6; Lung diseases; Lungs; Multiple regression analysis; Obstructive lung disease; Original; Regression analysis; Risk factors; Serum levels; Smoking; SP-A; SP-D; KL-6; SP-D; diabetes mellitus; insulin resistance; SP-A
• ISSN: 0918-2918; 1349-7235
• DOI: 10.2169/internalmedicine.8716-16

Objective Inflammatory cytokines generated in visceral fat have been shown to contribute to the development of insulin resistance. The involvement of pulmonary inflammation in insulin resistance remains unclear, but smoking is known to be a risk factor for diabetes as well as chronic obstructive pulmonary disease. We herein examined the hypothesis that increased serum levels of lung interstitial injury biomarkers [surfactant protein (SP)-A, SP-D and Krebs von den Lungen (KL)-6] are associated with the risk of diabetes development. Methods For cross-sectional and longitudinal analyses, we enrolled 750 apparently healthy non-diabetic subjects who received annual examinations in 2011 or 2012 in the Tanno-Sobetsu cohort. Results A cross-sectional analysis showed that distinct clinical parameters were associated with SP-A, SP-D and KL-6. In a multiple regression analysis, independent explanatory variables were Brinkman index and brain natriuretic peptide (BNP) for SP-A, sex (women), BNP and body mass index (BMI) for SP-D, and age and BMI for KL-6. A longitudinal analysis of 415 subjects who received annual examinations in both 2011 and 2014 showed that 13 (3.1%) of the patients developed type 2 diabetes during the 3-year follow-up. A multiple logistic regression analysis showed the KL-6 levels, systolic blood pressure and homeostasis model assessment of insulin resistance (HOMA-IR) in 2011 to be independently associated with new-onset diabetes. In a multiple regression analysis for HOMA-IR in 2014, the KL-6 level and BMI in 2011 were selected as explanatory variables. Conclusion A modest elevation of the serum KL-6 level is therefore considered to be associated with the risk for insulin resistance development and new-onset diabetes mellitus in a general population.