Endocrinol Metab.  2021 Dec;36(6):1254-1267. 10.3803/EnM.2021.1249.

Association between Lung Function and New-Onset Diabetes Mellitus in Healthy Individuals after a 6-Year Follow-up

• Lee HY
• Shin J
• Kim H
• Lee SH
• Cho JH
• Lee SY
• Kim HS

• KMID: 2523494
• DOI: http://doi.org/10.3803/EnM.2021.1249

Abstract

Background
We analyzed hemoglobin A1c (HbA1c) levels and various lung function test results in healthy individuals after a 6-year follow-up period to explore the influence of lung function changes on glycemic control.
Methods
Subjects whose HbA1c levels did not qualify as diabetes mellitus (DM) and who had at least two consecutive lung function tests were selected among the people who visited a health promotion center. Lung function parameters, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV/FVC ratio, and forced expiratory flow 25% to 75% (FEF_25%−75%), were divided into four groups based on their baseline quantiles. To evaluate future DM onset risk in relation to lung function changes, the correlation between baseline HbA1c levels and changes in lung function parameters after a 6-year follow-up period was analyzed.
Results
Overall, 17,568 individuals were included; 0.9% of the subjects were diagnosed with DM. The individuals included in the quartile with FEV1/FVC ratio values of 78% to 82% had lower risk of DM than those in the quartile with FEV1/FVC ratio values of ≥86% after adjusting for age, sex, and body mass index (P=0.04). Baseline percent predicted FEV1, FVC, FEV1/FVC ratio, and FEF_25%−75%, and differences in the FEV1/FVC ratio or FEF_25%−75%, showed negative linear correlations with baseline HbA1c levels.
Conclusion
Healthy subjects with FEV1/FVC ratio values between 78% and 82% had 40% lower risk for future DM. Smaller differences and lower baseline FEV1/FVC ratio or FEF_25%−75% values were associated with higher baseline HbA1c levels. These findings suggest that airflow limitation affects systemic glucose control and that the FEV1/FVC ratio could be one of the factors predicting future DM risk in healthy individuals.

Keyword

Diabetes mellitus; Airway obstruction; Respiratory function tests

Figure

• 

  Fig. 1. Linear plot between baseline lung function parameters and hemoglobin A1c (HbA1c, %). Percent predicted (A) forced vital capacity (FVC), (B) forced expiratory volume for 1 second (FEV1), (C) FEV1/FVC, and (D) forced expiratory flow 25% to 75% (FEF25%−75%) showed a significant negative correlation with baseline HbA1c.

• 

  Fig. 2. Linear plot between baseline hemoglobin A1c (HbA1c, %) and lung function changes for 6 years. Changes in percent predicted (A) forced vital capacity (FVC) and (B) forced expiratory volume for 1 second (FEV1) had a positive correlation with baseline HbA1c. In contrast, changes in (C) FEV1/FVC and (D) forced expiratory flow 25% to 75% (FEF25%−75%) showed a negative correlation with HbA1c.

Reference

1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011; 34 Suppl 1(Suppl 1):S62–9.

2. van den Borst B, Gosker HR, Zeegers MP, Schols AM. Pulmonary function in diabetes: a metaanalysis. Chest. 2010; 138:393–406.

3. Sonoda N, Morimoto A, Tatsumi Y, Asayama K, Ohkubo T, Izawa S, et al. The association between glycemic control and lung function impairment in individuals with diabetes: the Saku study. Diabetol Int. 2018; 10:213–8.

4. Sonoda N, Morimoto A, Tatsumi Y, Asayama K, Ohkubo T, Izawa S, et al. A prospective study of the impact of diabetes mellitus on restrictive and obstructive lung function impairment: The Saku study. Metabolism. 2018; 82:58–64.

5. Davis WA, Knuiman M, Kendall P, Grange V, Davis TM; Fremantle Diabetes Study. Glycemic exposure is associated with reduced pulmonary function in type 2 diabetes: the Fremantle Diabetes Study. Diabetes Care. 2004; 27:752–7.

6. Sanchez E, Gutierrez-Carrasquilla L, Barbe F, Betriu A, Lopez-Cano C, Gaeta AM, et al. Lung function measurements in the prediabetes stage: data from the ILERVAS Project. Acta Diabetol. 2019; 56:1005–12.

7. Cazzola M, Rogliani P, Calzetta L, Lauro D, Page C, Matera MG. Targeting mechanisms linking COPD to type 2 diabetes mellitus. Trends Pharmacol Sci. 2017; 38:940–51.

8. Enomoto T, Usuki J, Azuma A, Nakagawa T, Kudoh S. Diabetes mellitus may increase risk for idiopathic pulmonary fibrosis. Chest. 2003; 123:2007–11.

9. Kodolova IM, Lysenko LV, Saltykov BB. Changes in the lungs in diabetes mellitus. Arkh Patol. 1982; 44:35–40.

10. Spranger J, Kroke A, Mohlig M, Hoffmann K, Bergmann MM, Ristow M, et al. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes. 2003; 52:812–7.

11. Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2016; 138:16–27.

12. Fogarty AW, Lewis SA, McKeever TM, Britton J. The association of two different measures of body habitus with lung function: a population-based study. Respir Med. 2011; 105:1896–901.

13. Sheen YJ, Hsu CC, Jiang YD, Huang CN, Liu JS, Sheu WH. Trends in prevalence and incidence of diabetes mellitus from 2005 to 2014 in Taiwan. J Formos Med Assoc. 2019; 118 Suppl 2:S66–73.

14. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005; 26:319–38.

15. Choi JK, Paek D, Lee JO. Normal predictive values of spirometry in Korean population. Tuberc Respir Dis. 2005; 58:230–42.

16. Ford ES, Mannino DM; National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Prospective association between lung function and the incidence of diabetes: findings from the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Diabetes Care. 2004; 27:2966–70.

17. Lazarus R, Sparrow D, Weiss ST. Baseline ventilatory function predicts the development of higher levels of fasting insulin and fasting insulin resistance index: the Normative Aging Study. Eur Respir J. 1998; 12:641–5.

18. Wannamethee SG, Shaper AG, Rumley A, Sattar N, Whincup PH, Thomas MC, et al. Lung function and risk of type 2 diabetes and fatal and nonfatal major coronary heart disease events: possible associations with inflammation. Diabetes Care. 2010; 33:1990–6.

19. Yeh HC, Punjabi NM, Wang NY, Pankow JS, Duncan BB, Brancati FL. Vital capacity as a predictor of incident type 2 diabetes: the Atherosclerosis Risk in Communities study. Diabetes Care. 2005; 28:1472–9.

20. Zaigham S, Nilsson PM, Wollmer P, Engstrom G. The temporal relationship between poor lung function and the risk of diabetes. BMC Pulm Med. 2016; 16:75.

21. Alicandro G, Battezzati PM, Battezzati A, Speziali C, Claut L, Motta V, et al. Insulin secretion, nutritional status and respiratory function in cystic fibrosis patients with normal glucose tolerance. Clin Nutr. 2012; 31:118–23.

22. Nezer N, Shoseyov D, Kerem E, Zangen DH. Patients with cystic fibrosis and normoglycemia exhibit diabetic glucose tolerance during pulmonary exacerbation. J Cyst Fibros. 2010; 9:199–204.

23. Kwon CH, Rhee EJ, Song JU, Kim JT, Kwag HJ, Sung KC. Reduced lung function is independently associated with increased risk of type 2 diabetes in Korean men. Cardiovasc Diabetol. 2012; 11:38.

24. Nadeau KJ, Anderson BJ, Berg EG, Chiang JL, Chou H, Copeland KC, et al. Youth-onset type 2 diabetes consensus report: current status, challenges, and priorities. Diabetes Care. 2016; 39:1635–42.

25. Karampatakis N, Karampatakis T, Galli-Tsinopoulou A, Kotanidou EP, Tsergouli K, Eboriadou-Petikopoulou M, et al. Impaired glucose metabolism and bronchial hyperresponsiveness in obese prepubertal asthmatic children. Pediatr Pulmonol. 2017; 52:160–6.

26. Ali-Dinar T, Lang JE. Is impaired glucose metabolism the missing piece in the obesity-asthma puzzle? Pediatr Pulmonol. 2017; 52:147–50.

27. Kim KM, Kim SS, Lee SH, Song WJ, Chang YS, Min KU, et al. Association of insulin resistance with bronchial hyperreactivity. Asia Pac Allergy. 2014; 4:99–105.

28. Cavalher-Machado SC, de Lima WT, Damazo AS, de Frias Carvalho V, Martins MA, e Silva PMR, et al. Down-regulation of mast cell activation and airway reactivity in diabetic rats: role of insulin. Eur Respir J. 2004; 24:552–8.

29. Lessmann E, Grochowy G, Weingarten L, Giesemann T, Aktories K, Leitges M, et al. Insulin and insulin-like growth factor-1 promote mast cell survival via activation of the phosphatidylinositol-3-kinase pathway. Exp Hematol. 2006; 34:1532–41.

30. Belmonte KE, Jacoby DB, Fryer AD. Increased function of inhibitory neuronal M2 muscarinic receptors in diabetic rat lungs. Br J Pharmacol. 1997; 121:1287–94.

31. Park YH, Oh EY, Han H, Yang M, Park HJ, Park KH, et al. Insulin resistance mediates high-fat diet-induced pulmonary fibrosis and airway hyperresponsiveness through the TGF-β1 pathway. Exp Mol Med. 2019; 51:1–12.

32. Celli BR, MacNee W; ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004; 23:932–46.

33. Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005; 26:948–68.

34. Ciprandi G, Cirillo I. The pragmatic role of FEF25-75 in asymptomatic subjects, allergic rhinitis, asthma, and in military setting. Expert Rev Respir Med. 2019; 13:1147–51.

35. Kwon DS, Choi YJ, Kim TH, Byun MK, Cho JH, Kim HJ, et al. FEF25-75% values in patients with normal lung function can predict the development of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2020; 15:2913–21.

36. Lovic D, Piperidou A, Zografou I, Grassos H, Pittaras A, Manolis A. The growing epidemic of diabetes mellitus. Curr Vasc Pharmacol. 2020; 18:104–9.

37. Little RR, Rohlfing C, Sacks DB. The National Glycohemoglobin Standardization Program: over 20 years of improving hemoglobin A1c measurement. Clin Chem. 2019; 65:839–48.

38. Laaksonen DE, Lindstrom J, Lakka TA, Eriksson JG, Niskanen L, Wikstrom K, et al. Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study. Diabetes. 2005; 54:158–65.

39. Lindstrom J, Peltonen M, Tuomilehto J. Lifestyle strategies for weight control: experience from the Finnish Diabetes Prevention Study. Proc Nutr Soc. 2005; 64:81–8.

40. Baker MK, Simpson K, Lloyd B, Bauman AE, Singh MA. Behavioral strategies in diabetes prevention programs: a systematic review of randomized controlled trials. Diabetes Res Clin Pract. 2011; 91:1–12.