Aging Lungs Fail Faster with Type 2 Diabetes

By Michael Smith
BALTIMORE, March 28 -- Lung function declines faster in type 2 diabetes patients than in those without the disease, according to researchers here.
Point out that the study is subject to residual confounding and cannot prove causality.
The finding -- from the long-running Atherosclerosis Risk in Communities (ARIC) study -- implies that clinicians should pay attention to pulmonary function in diabetic patients, said Frederick Brancati, M.D., of Johns Hopkins and colleagues.
It also may have implications for the use of inhaled forms of insulin, Dr. Brancati and colleagues said in the April issue of Diabetes Care.
"The results suggest that doctors and patients should keep an eye on the literature about diabetes and the lung down the road, since there's a stronger connection than we previously thought," Dr. Brancati said.
"Manufacturers of inhaled insulin should find these data useful as they study potential long-term effects of their product on lung function," Dr. Brancati added.
For this analysis, he and colleagues looked at lung function in 1,100 middle-age patients with diabetes and 10,162 persons without it enrolled in the ARIC study. Key measures were forced vital capacity (FVC) and one-second forced expiratory volume (FEV1), measured at baseline and after three years.
At baseline, the researchers found:
FVC in men and women with diabetes was 4.2 and 3.0 liters, respectively, compared with 4.6 and 3.3 in non-diabetic men and women. The differences were significant at P<0.001.
Similarly, FEV1 in men and women with diabetes was 3.2 and 2.3 liters, respectively, compared with 4.3 and 2.5 in non-diabetic volunteers. Again the differences were significant at P<0.001.
FVC percentage predicted and FEV1 percentage predicted were also significantly lower in patients with diabetes.
When the researchers stratified the diabetic patients according to fasting glucose levels, duration of diabetes, and use of diabetic medications at baseline, they found a graded inverse association between those characteristics and FVC and FEV1. In all cases, the trend was significant at P<0.001.
Three years further on, Dr. Brancati and colleagues found the non-diabetics has suffered an average decline of 58 mL per year in FVC, compared with 64 mL a year for the diabetics. The difference was significant a P<0.01.
The non-diabetics had also lost 47 mL per year of FEV1 compared with 49 for the diabetics, but the difference was not significant.
FVC percentage predicted declined significantly (P=0.009) but FEV1 percentage predicted was no longer significantly different. Also, fasting glucose levels and duration of diabetes were no longer significantly associated with most lung function measures.
However, the use of insulin (compared with no medications or the use of oral agents) remained significantly associated (Ptrend =0.001) with lower FVC, the researchers found.
The study "essentially confirms" some previous research, commented Connie Hsia, M.D. and Philip Raskin, M.D., both of the University of Texas Southwestern Medical Center in Dallas, in an accompanying editorial.
But other studies have suggested that the difference between diabetics and non-diabetics in lung function does not continue to increase over time, they wrote.
If Dr. Brancati and colleagues are correct, they said, the lung should be thought of as a "as a crime victim who unwittingly abets the perpetrator to hasten the demise of the host."
In other words, cumulative loss of lung function eventually worsens tissue hypoxia associated with angiopathy in distant organs and increases diabetic morbidity and mortality, they said.
But proving that model is correct "beyond reasonable doubt remains a daunting challenge, they concluded.
They also pointed out some important limitations. They noted that there were more African Americans (37% versus 21%, P<0.001) and a higher mean BMI (30.9 versus 27.2, P<0.001) among the diabetic patient group,
They noted that "average FVC and FEV1 are lower in African Americans than in Caucasians after adjustment for sex, age, and height," and that "adiposity independently impairs lung function."
The authors also noted the importance of the difference in BMI stating that "given the strong relation between type 2 diabetes and central adiposity, even the most meticulous adjustment for BMI and waist circumference leaves some concern about the possibility of residual confounding."
The ARIC Study is supported by the National Heart, Lung, and Blood Institute, the National Institute of Diabetes, Digestive, and Kidney Diseases NIDDK). Individual researchers were supported by the NIH, the Brazilian National Research Council, and the NIDDK. Analysis of this manuscript was partly supported by Pfizer. Dr. Brancati reported no conflicts.
Dr. Raskin reported financial links with Novo Nordisk, Pfizer, and MannKind.
Primary source: Diabetes CareSource reference:Yeh H-C et al "Cross-sectional and prospective study of lung function in adults with type 2 diabetes: The atherosclerosis risk in communities (ARIC) study" Diabetes Care 2008; 31: 741-746. Additional source: Diabetes CareSource reference: Hsia CW, Raskin P "Lung involvement in diabetes: Does it matter?" Diabetes Care 2008; 31: 828-28.