In the current study, diabetes, IGT, and levels of metabolic biomarkers in adults with NGT were inversely and independently associated with lung function in community-dwelling, nonsmoking African American adults who were free of clinical CVD. These associations varied by sex. Women with diabetes and IGT had significantly lower FEV1, FEV6, and FVC % predicted values compared to women with NGT, with differences averaging approximately 4–6 and 3–5%, respectively. The mean differences in lung function between women with IGT and NGT did not persist after adjustment for waist circumference. Men with diabetes had significantly lower lung function than men with NGT. No significant associations between uncontrolled diabetes and duration of diabetes and lung function were observed in women or men. Lower lung function was consistently associated with higher glucose and less consistently with higher insulin, IR, and HbA1c levels in women with NGT. In men with NGT, lower lung function was consistently associated with higher insulin and IR levels; no associations were observed between lung function and glucose and HbA1c in men. These associations persisted after adjustment for waist circumference and other potential confounders.
Our findings are consistent with previous studies that explored the associations of diabetes and lung function in cohorts of elderly [13
], predominantly white [5
], and US [6
] samples. Our findings extend the literature by investigating the associations between glycemia and lung function in middle-aged and elderly African Americans and estimating lung function in individuals with IGT (i.e., prediabetes). Although the associations between IGT and lung function in African Americans were attenuated after adjustment for waist circumference, the findings observed among African American women with IGT supports the hypothesis of declines in lung function early in the development of diabetes. The lack of association in men may be explained by other physiological processes. Glucose metabolism occurs in the adipose (and muscle) tissue of the abdomen and higher insulin concentrations are needed in the presence of increased adipose tissue volumes in order to enable the body to properly absorb glucose. Men in this cohort have been shown to have higher visceral adipose tissue (VAT) volumes than women [30
]. This may contribute to the production of higher concentrations of insulin in the body, resulting in reduced lung function in men. Moreover, the lack of associations between diabetes control and duration of diabetes in women and men in this cohort may be due to the small number of participants with severe uncontrolled diabetes (mean = 7.9 ± 1.8%), or the small number of participants with a prolonged duration of diabetes (mean = 10.3 ± 9.3 years). A study among older adults, however, reported that duration of diabetes (>10 years) was associated with lower FEV1
and FVC in white men only [16
Prior work that examined the associations of metabolic biomarkers with lung function is more obscure. First, studies examining these associations have been confounded by smokers and individuals with IGT and the findings have been mixed [6
]. Second, few studies have investigated differences by sex. In the present study, we observed significant heterogeneity in the association between metabolic biomarkers and lung function by sex. In addition, in our sample of nonsmoking adults with NGT, we observed that lower lung function was consistently associated with higher glucose levels in women and higher insulin levels and IR in men. In the predominantly white Rancho Bernardo Study, plasma glucose levels were inversely associated with FEV1
and FVC in men without diabetes, but not in women. Investigators from the British Women's Heart and Health Study [7
] reported that IR was inversely associated with these lung function measures among nonsmoking British women who were 60–79 years of age after adjusting for height, BMI, waist-to-hip ratio, physical activity, white blood cell count, socioeconomic status, and respiratory medication use. Burchfiel et al. [13
] reported that fasting insulin was inversely associated with FVC in elderly Japanese American men with a history of smoking. These studies, however, did not exclude individuals with IGT, which may contribute to differences in these findings (notwithstanding obvious racial/ethnic and geographic differences).
Diabetes is a metabolic disease marked by high levels of glucose in the blood and is linked to conditions such as retinopathy, neuropathy, and nephropathy [31
]. Lung injury occurs via microangiopathy—structural and functional alterations of capillaries in the alveolar septa and arterioles—in states of diabetes [32
]. Lung biopsies from patients with diabetes have shown thickening of the alveolar epithelial and endothelial capillary basal lamina [32
]. An animal study observed narrowing of the lumen of alveolar capillary endothelial cells and an uneven distribution of the anionic sites of endothelial capillaries exposed by the luminal plasmalemma [33
]. In human lungs, structural and functional changes in the state of diabetes also include the alteration of the biochemistry of connective tissue in the human lungs [34
]. The most consistent abnormalities are reduced volumes and elastic recoil, which results from increased lysyl oxidase activity and glycosylation-induced compositional changes of collagen [34
The mechanisms that explain the relationships of metabolic biomarkers with lung function in women and men may reflect different physiologic pathways. The inverse association of insulin with lung function (except for FVC) in women did not remain significant after adjustment for waist circumference, suggesting that other metabolic dysregulations in states of obesity, possibly systemic and vascular inflammation, contribute to reduced lung function in women. The association of HbA1c with lung function in women and men may be expected since HbA1c is a glucose-protein derivative and reflects an integrated measure of glucose control in the body over time. Men have been shown to have greater VAT volumes than women [30
], and greater intra-abdominal fat in the abdomen has been shown to play an important role in the development of IR [36
] and reduced lung function [37
]. Additional investigations with longitudinal study designs and multiethnic populations are needed to fully understand lung function in states of NGT.
Causal pathways of GT, diabetes control and duration of diabetes, and metabolic biomarkers in individuals with NGT and lung function cannot be inferred from cross-sectional analyses such as the current study. The general consistency and strength of these relationships in different racial/ethnic populations, however, indicate that GT and metabolic biomarkers play an important role in reduced lung function. However, emerging evidence hypothesizes that reduced lung function is a predictor of incident diabetes [10
], suggesting a potential bidirectional relationship. The fact that our sample consisted of generally healthy adults who never smoked supports the hypothesis that the lungs are a target organ in diabetes and glycemia. The exposure to environmental tobacco smoke and other environmental toxicants cannot be dismissed. Studies have observed that environmental tobacco smoke and chronic exposure to traffic-related pollution is associated with reduced lung function [39
]. Environmental pollution levels are considerably lower in this region of the US compared to other metropolitan areas and the geographic regions in which participants were sampled are predominantly mixed urban–rural and rural areas [41
]. Thus, we are not led to believe that such exposures would mediate the findings reported in this study.
Overall, our findings support the hypothesis that diabetes, IGT, and higher levels of metabolic biomarkers in individuals with NGT are associated with reduced lung function in African Americans, generally after adjustment for abdominal adiposity. There is a growing literature that demonstrates an increased cardiovascular risk among persons with reduced lung function [1
]. If the role of diabetes and impaired fasting glucose in respiratory health is confirmed [42
], glucose and other metabolic biomarkers may represent a pathway through which impaired lung function is related to CVD and other chronic diseases.