Table 5 Some of the key studies assessing the impact of type 2 DM/MetS on the pulmonary function and COPD

Guazzi et al.[149]; 2002

Italy

In hospital study assessing the effects of regular insulin on the alveolar-capillary conductance.

n: 19 patients (11 men) with type 2 DM and normal cardiac function. mean age: 59.9 years mean weight: 75.8 kg.

DLCO and alveolar capillary membrane conductance were increased by 12% and 14% respectively by insulin therapy.

DLCO and its subcomponents were measured.

Guazzi et al.[150]; 2002

Italy

Cross-sectional study.

n: 30 patients with HF (19 men), 15 patients with type 2 DM (8 men) and 15 controls (8 men). mean age: 61.1 years for controls, 62.3 years for patients with type 2 DM, 62.8 years for patients with type 2 DM and HF and 64.1 years for patients with HF alone. mean weight: 75.2 kg for patients with HF and type 2 DM, 76.1 kg for patients with type 2 DM, 76.7 kg for patients with HF and 77.8 kg for controls.

Patients with type 2 DM had a lower DLCO than controls.

Regular insulin improved DLCO in patients with type 2 DM and type DM and HF, with no improvement in patients with HF alone. The improvement in patients with type 2 DM and HF was greater than in patients with type 2 DM alone.

Guvener et al.[157]; 2003

Turkey

Cross-sectional study.

n: 25 patients with type 2 DM (9 men) and 12 healthy controls (4 men). mean age: 56.3 years for patients with type 2 DM and 50.1 years for controlsmean BMI: 29.9 kg/m² for patients with type 2 DM and 29.5 kg/m² for controls.

Patients with type 2 DM had lower ratio of DLCO to VA. In a stepwise regression model with inclusion of age, duration of type 2 DM and microalbuminuria, only microalbuminuria was found to be independent predictor of DLCO/VA.

Chance et al.[158]; 2008

USA

Cross-sectional study assessing alveolar capillary bed in patients with type 2 DM.

n: 69 never smokers with type 2 DM and no overt cardiopulmonary disease (46% women) vs. 45 controls (45% women). mean age: 45 years for controls, 49 years for patients with type 2 DM and BMI>30 kg/m² and 45 years for patients with type 2 DM and BMI<30 kg/m². mean BMI: 28.8 kg/m2 for controls, 27.4 kg/m² and 34.4 kg/m² for aforementioned type 2 DM groups respectively.

Both non-obese (BMI<30 kg/m²) and obese (BMI≥30 kg/m²) patients with type 2 DM had reduced levels of the measured pulmonary function variables during exercise. However, the observed changes in obese patients were not fully explained by the baseline lung volumes. Moreover, the presence of retinopathy, neuropathy, microalbuminuria and control of diabetes were associated with the reduced pulmonary microvascular reserve

Niranjan et al.[166]; 1997

USA

Prospective observational study of cardio-pulmonary function at 7 years of follow up. Aerobic exercise capacity was measured with cycle ergometry. Lung volume and diffusing capacity were measured with rebreathing technique and ventialatory power was measured by esophageal balloon technique.

n: 18 subjects with type 1 DM (11 men) and 14 controls (10 men). mean age: 31 years for controls and 39 for patients with type 1 DM. mean BMI: 22 kg/m² for controls and 24.91-25.49 kg/m² among patients with type 1 DM.

Patients with poor glycemic control had worse restriction of lung volume, pulmonary diffusing capacity and membrane diffusing capacity. Cardiac stroke index was reduced among subjects with poor glycemic control.

In the long-term analysis the rate of FEV₁ and FVC decline was similar to those without DM.

Saler et al.[170]; 2009

Turkey

Cross-sectional study assessing alveolar capillary bed in patients with type 1 and type 2 DM.

n: 44 subjects with type 1 DM (29 women), 68 subjects with type 2 DM (49 women) and 80 controls (58 women). mean age: 32.52 years for patients with type 1 DM, 52.4 years for patients with type 2 DM and 40.08 years for controls. mean BMI: 24.4 kg/m² for patients with type 1 DM, 27.0 kg/m² for patients with type 2 DM and 25.6 kg/m² for controls.

DLCO and the ratio of DLCO to VA were significantly decreased in patients with both types of DM, but not in control group.

Wanke et al.[184]; 1991

Austria

Cross-sectional study.

n: 36 patients with type 1 DM (31 men) and 40 controls (33 men). mean age: 33 years for patients with DM and 27 years for controls. mean BMI: 24.3 kg/m² for patients with DM and 22.3 kg/m² for controls.

Patients with type 1 DM had significantly lower inspiratory VC, which was in part explained by reduced maximal sniff transesophageal and transdiaphragmatic pressures in patients with type 1 DM.

Walter et al.[194]; 2003

USA

Prospective observational study with a follow up>15 years using the data of the Framingham Heart Study.

n: 3,254 (1,547 men) with 280 subjects having type 2 DM mean age: 53.9 years for patients without type 2 DM and 59.6 years for patients with type 2 DM. mean BMI: 27.3 kg/m² for patients without type 2 DM and 30.67 kg/m² for patients with type 2 DM.

Patients with type 2 DM had a lower mean FEV₁, FVC. The FVC/FEV₁ ratio was slightly higher in patients with type 2 DM.

Higher fasting glucose levels had association with decreased FEV₁, FVC and FVC/FEV₁ ratio (only in current smokers).

Lawlor et al.[195]; 2004

UK

Cross-sectional study.

N: 3,911 women (9.8% had type 2 DM).

FEV1 and FVC were inversely related to the HOMA score.

Age: post-menopausal women aged 60–79 years

After adjustment for age, anthropometric variables, smoking, physical activity, childhood and adult social class and respiratory medications the higher FEV₁ and FVC were associated with decrease in HOMA score of 3% and 5% respectively.

Mean BMI: not provided.

Patients with higher values of FEV₁ and FVC had lower prevalence of DM.

Davis et al.[196]; 2004

Australia

Prospective study using the data from the Fremantle Diabetes Study with a mean follow up of 7 years.

n: 125 subjects with type 2 DM. mean age: 61.5 years mean BMI: 29.9 kg/m²

Higher follow up fasting glucose, greater levels of follow up HbA1c and mean updated HbA1c were associated with a decrease in measured pulmonary parameters.

FEV1, FVC, VC and PEF were measured at baseline and during follow up.

Decreased FEV₁ was found to be independent predictor of all-cause mortality.

McKeever et al.[197]; 2005

UK

Study analyzing the data of the NHANES III.

n: 4,257 (1,943 men) mean age: 37 years mean BMI: 27.0 kg/m²

Patients with higher 2 hour 75 g glucose tolerance test had lower levels of FEV₁ and FVC.

Patients with a history of DM had lower levels of FEV₁ and patients with poor control of DM had lower FEV₁ than patients with controlled DM.

Litonjua et al.[198]; 2005

USA

A nested case–control study using the data of Normative Aging Study.

n: 352 men who developed type 2 DM and 352 controls (all men) mean age: 43.1 years for patients with type 2 DM and 43.2 years for controls. mean BMI: 26.81 kg/m² for patients with type 2 DM and 25.31 kg/m² for controls.

Patients with type 2 DM had lower FEV₁ and FVC values (but not FEV₁/FVC) many years prior to the diagnosis of type 2 DM.

However, there was no difference in the rate of annual decline of FEV1 and FVC in patients with type 2 DM and controls.

Baker et al.[207]; 2006

UK

Cross-sectional study in patients admitted with acute exacerbation of COPD.

n: 284 subjects (167 men) mean age: from 72.9 to 76.7 years (depends on the glucose quartile, with higher glucose associated with older age) mean BMI: not provided

The RR of death and long hospital stay was greater in patients with glucose from 7.0-8.9 mmol/l and >9.0 mmol/l (RR 1.46 and 1.97 espectively), which was independent from age, gender, COPD severity and prior diagnosis of DM.

The patients were divided into 3 groups based on the glucose quartile (<6.0mmol/l, 6.0-6.9 mmol/l 7.0-8.9 mmol/l and >9 mmol/l)

Each mole increase in glucose was associated with 15% greater risk for adverse clinical outcome.

Higher glucose level was associated with the isolation of Staphylococcus Aureus from the sputum.

Chakrabarti et al.[208]; 2009

UK

An observation study on the effects of hyperglycemia on the outcome of non-invasive ventilation (NIV) during COPD exacerbation.

n: 88 in hospital patients (39 men). mean age: 70 years mean BMI: data not provided

Random blood glucose≥7.0 mmol/l was independently associated with an adverse NIV outcome such as NIV failure and greater risk for pneumonia.

Küpeli et al.[209]; 2010

Turkey

An observational study assessing the correlation between the presence of MetS and COPD exacerbation rate.

n: 106:29 patients with MetS (24 men) and 77 patients without MetS (67 men). mean age: 64.9 years for patients with MetS and 67.3 years for patients without MetS.mean BMI: 30.3 kg/m² for patients with MetS And 27.2 kg/m² for patients without MetS.

The mean COPD exacerbation rate was 2.4 in MetS group compared to 0.68 in the control group. Mean length of each exacerbation was 7.5 days in patients with MetS compared to 5 days in patients without MetS. Serum C-reactive protein, fasting blood glucose, and triglycerides were positively correlated with COPD exacerbation rate.