Journal of Pulmonary Medicine & Respiratory Research Category: Medical Type: Research Article
Association Between Increased Insulin Resistance Index HOMA-IR and COPD in a Nationally Representative Population Sample
- Merja Kanervisto1*, Laitinen Tarja2, Saarelainen Seppo3, Vasankari Tuula4, Heliövaara Markku5, Jousilahti Pekka5, Lahtela Jorma6
- 1 School Of Health Sciences, University Of Tampere, Tampere, Finland
- 2 Department Of Pulmonary Diseases, Turku University Hospital, Turku, Finland
- 3 Departments Of Respiratory Medicine And Psychiatry, Tampere University Hospital, Tampere, Finland
- 4 Finnish Lung Health Association, Helsinki, Finland
- 5 National Institute For Health And Welfare, Helsinki, Finland
- 6 Department Of Internal Medicine, Tampere University Hospital, Tampere, Finland
*Corresponding Author:Merja Kanervisto
School Of Health Sciences, University Of Tampere, Tampere, Finland
Received Date: Oct 11, 2015 Accepted Date: Nov 26, 2015 Published Date: Dec 17, 2015
Research design and methods: The data consisted of the participants (N = 8028) of a health examination survey conducted in Finland in 2000-2001. In the present study spirometry verified COPD after exclusion of asthma and diabetes was 3.7% (216/5892) of the subjects.
Results: In an adjusted logistic regression model increased HOMA-IR index had a significant association with COPD (OR 1.8, 95% CI 1.2 - 2.5). Adjusted linear regression model showed the association between HOMA-IR index and lack of exercise those in people with COPD (p < 0.05). Correlation between smoking and HOMA-IR index was significant (p < 0.01), but despite this in current smokers the HOMA-IR index was lower than in people with COPD who had quit or were never smokers (p < 0.001), there was also significant differences with the mean of BMI between those three smoking groups (p < 0.001).
Conclusion: In this large population based survey insulin resistance had a significant association with COPD. Further prospective studies are needed to confirm this association. Special attention should be paid to the inactivity and over weight in people with COPD.
The Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index has been developed to assess the pancreatic beta cell function. It describes this glucose-insulin homeostasis by means of a set of simple, mathematically derived nonlinear equations. The approximating equation for IR has been simplified and uses a fasting plasma sample in which glucose and plasma insulin are measured . Insulin resistance is a key factor in the pathogenesis of type 2 diabetes. HOMA-IR is an independent predictor of type 2 diabetes . The correlation between Cardiovascular Diseases (CVD) and insulin resistance has been known . It is also noticed that type 2 diabetes  and insulin resistance  are associated with impaired lung function.
Smoking is a main causative factor for COPD. As a part of the Copenhagen City Heart Study, total of 8045 men and women aged 30 - 60 years with normal lung function were followed for 25 years in Løkke et al., study . They found that the longer people smoked, the higher the risk for developing COPD was. The highest incidence for all stages of COPD was 35.5% for those who had smoked over the 25 years, while the incidence for never smokers was 7.8%. They found that of continuous smokers 24.3% developed clinically significant COPD in stage 2 or worse. In addition to smoking, obesity is important risk factor of many chronic diseases. Overweight can impair respiratory function. Smoking  and obesity both are associated with insulin resistance, oxidative stress and increase of variety of inflammatory markers such as CRP and cytokines discharge . Obesity, smoking and systemic inflammation may play role to develop metabolic syndrome .
Body Mass Index (BMI) is an important parameter to assess functional status of people with COPD and disease severity . In Yamauchi et al., study they suggest that overweight and obese COPD patients had a lower mortality than those with low or normal weight .
In Hsiao FC et al.,  study a reduction in FEV1 is proposed and useful predictor of the metabolic syndrome. We assessed the association with insulin resistance and COPD in a large nationwide population-based study. The aim of this study was to evaluate the association of the HOMA-IR index with COPD in adult (age ≥ 30) Finnish population.
MATERIAL AND METHODS
Study design and subjects
Definition of COPD, insulin resistance and other study determinants
The homeostatic index of HOMA-IR was calculated as described by Matthews et al.,: glucose level (mmol/l) × insulin level (mmol/l)/22.5 . Low HOMA-IR values indicate high insulin sensitivity, whereas high HOMA-IR values indicate insulin resistance. The HOMA-IR index ≥ 2.5 indicates insulin resistance  and this cut-off was used in this study.
Smoking was classified in four groups: daily smokers, occasionally smokers, quit smoking and never smokers. In the present study smoking was classified in three groups: current smokers, quit smoking and never smokers and then in two groups: smoking yes or no.
Blood samples for serum high sensitive C-Reactive Protein (hsCRP) determination were drawn during the clinical examination after 4 hours of fasting as described by Stenholm et al., .
Body Mass Index (BMI, weight/height2, kg/m2) was computed as a measure of relative weight.
Exercise capacity indicates what a person is capable to do . Summated variable of exercise capacity was formed in accordance with 5 questions of mobility. A high score was considered to represent good active exercise behavior. Self-reported items concerned ability to walk for a 2 km or ½ km or climb stairs in one or more floors without resting, difficulty walking from one room to another on the same level. Questions are based on OECD recommendations (McWhinnie 1981) . In addition, blood pressure values were considered, as well as cholesterol levels from the study group.
|Characteristics||COPD (N = 216)||No COPD (N = 4876)|
|Men||136 (63.0%)||2236 (45.9%)|
|Woman||80 (37.0%)||2640 (54.1%)|
|Age, mean (SD)||67.5 (±13.0)||50.5 (± 13.7)|
|BMI, mean (SD)||25.8 (± 4.6)||26.7 (± 4.4)|
|Currently||91 (42.1%)||1325 (27.2%)|
|Quit||58 (26.9%)||1024 (21.0%)|
|Never||67 (31.0%)||2527 (51.8%)|
|FP-glucose, mean (SD)||5.6 (0.6)||5.4 (± 0.6)|
|< 7.1||211 (97.7%)||4804 (98.5%)|
|≥ 7.1||5 (2.3%)||72 (1.5%)|
|HOMA-IR index, mean (SD)||2.4 (± 2.2)||2.0 (± 1.8)|
|S-hsCRP mg/l, mean (SD)||3.1 (± 5.4)||2.0 (± 4.9)|
|Good or adequate||115 (53.2%)||4068 (83.4%)|
|Lack of exercise||101 (46.8%)||808 (16.6%)|
|FEV1% of predicted, mean (SD)||72.5 (±17.9)||96.5 (±13.2)|
After adjustment for exercise, BMI, smoking, hs-CRP, gender, age in the multivariate logistic regression analysis HOMA-IR index ≥ 2.5 was an risk factor for COPD (OR 1.8, 95% CI 1.2 - 2.5), and remained an independent determinant for COPD (OR 1.1, 95% CI 1.0 - 1.1) (Table 2).
|OR||95% CI||P-value||OR||95% CI||P-value|
|≥ 2.5||1.1||1.0 - 1.1||0.003||1.8||1.2 - 2.5||0.002|
|Good or adequate||1|
|Lack of exercise||4.4||3.3 - 5.8||0.000||1.5||1.0 - 2.1||0.042|
|BMI||1.0||0.9 – 1.0||0.002||0.9||0.9 - 0.9||0.000|
|Quit||2.3||1.5 - 3.1||0.000||1.8||1.2 - 2.8||0.005|
|Current||6.7||4.4 - 10.2||0.000|
|1.0 - 1.0||0.003||1.0||1.0 - 1.0||0.767|
|Men||2.0||1.4 - 2.7||1.4 - 2.7||1.9||1.4 - 2.6||0.000|
|Age||1.1||1.1 - 1.1||0.000||1.1||1.1 - 1.1||0.000|
A significant regression equation was found between HOMA-IR index and lack of exercise (F1, 214) = 23,580, p < 0.05), with an R2 of 0.013. In people with COPD 1.3% of the total variation in HOMA-IR index can be explained by the linear relationship HOMA-IR index and lack of exercise, when adjusted with FEV1% of predicted (Table 3).
|HOMA-IR index||β||P - value|
|Lack of Exercise ||0.146||0.035|
|FEV1% of predicted||-0.007||0.92|
The correlation between HOMA-IR index and smoking was found to be statistically significant, r = 0.202, p < 0.01, two - tailed. The HOMA-IR index was higher in quitters than current smokers and highest among never smokers (Figure 2), p < 0.001. BMI among different smoking categories is in figure 2 (p < 0.001).
In our study we found a relationship between HOMA-IR index and lack of exercise among COPD subjects. It has been shown that physical inactivity increases the risk of those with COPD to develop metabolic syndrome [22,23]. Skeletal muscle weakness is common in people with COPD . Insulin resistance may be an important mechanism in the development of skeletal muscle weakness . Exercise training aims to modify skeletal muscle function to enhance exercise capacity  and may confer an increase in physical activity. Also the level of physical activity is most important factor in determining self - reported general health and health related quality of life in people with COPD [27,28].
Obesity is often the main cause of increased HOMA-IR index, insulin resistance  as well as physical inactivity, and especially abdominal obesity is associated with worsening lung function [30,31]. Some diseases as cardiovascular diseases, type 2 diabetes and the metabolic syndrome, in turn, are associated with an elevated waistline [32,33]. Intensive lifestyle interventions as diet and exercise can reduce the incidence of type 2 diabetes of those people in risk . Smoking in the study group was studied by the smoking habits: current, quit or never smokers, BMI and hsCRP was included to the analysis as a confounding factor of metabolic syndrome. COPD varies with age and smoking status , it rarely occurs in people under 40 years old, and COPD is more common for males than females , our study confirmed that. Even if there was a positive correlation between smoking and HOMA-IR index, we suggest that obese never smokers and also those who had quit smoking with severe obesity had significantly higher insulin resistance index than the current smokers.
In conclusion, our results suggest that increased HOMA-IR index ≥ 2.5 has significant association with COPD. The strength of our study was the large study population representative of the Finnish adults and the exceptionally high participation rate. However, further longitudinal studies are needed to confirm the relationship of the association. Specific attention should be paid to inactivity and obesity in people with COPD.
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Citation: Kanervisto M, Tarja L, Seppo S, Tuula V, Markku H, et al. (2015) Association Between Increased Insulin Resistance Index HOMA-IR and COPD in a Nationally Representative Population Sample. J Pulm Med Respir Res 1: 001. 1.
Copyright: © 2015 Merja Kanervisto, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.