Decline of neuroadrenergic bronchial innervation and respiratory function in type 1 diabetes mellitus: a longitudinal study.
OBJECTIVE
Type 1 diabetes mellitus complicated by autonomic neuropathy (AN) is characterized by depressed cholinergic bronchomotor tone and neuroadrenergic denervation of the lung. We explored the effects of AN on the rate of decline of pulmonary sympathetic innervation and respiratory function during a 5-year follow-up.


METHODS
Twenty diabetic patients, 11 with AN, were enrolled in 1998 and then followed-up until 2003. During follow-up, glycosylated haemoglobin (HbA1c) was measured every 3 months. In 1998 and 2003 the patients underwent respiratory function tests and a ventilatory scintigraphic study of neuroadrenergic bronchial innervation using 123I-MIBG.


RESULTS
During follow-up 4 patients, all with AN, were lost, and 1 developed AN. Forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) showed comparable rates of decrease in patients with and without AN. The yearly decline of forced expiratory volume in 1 s (FEV1) was about double the physiologic rate, in both AN and AN-free patients. The MIBG clearance significantly increased both in patients with AN (T1/2: 118.88 +/- 30.14 min at baseline and 92.10 +/- 24.52 min at the end of follow-up) and without AN (135.14 +/- 17.09 min and 92.68 +/- 13.52 min, respectively), indicating a rapidly progressive neuroadrenergic denervation. The rate of the neuroadrenergic denervation was inversely related to the severity of autonomic dysfunction at baseline (Spearman's rho - 0.62, p = 0.017). Neither respiratory function indexes nor MIBG clearance changes correlated with the overall HbA1c values.


CONCLUSIONS
Neuroadrenergic denervation of the lung parallels the decline of respiratory function indexes in diabetic patients both with and without AN and seems to be independent from the quality of glycemic control.
Antonelli Incalzi
Raffaele
R
Department of Geriatrics Campus Biomedico University, Rome, Italy.
Fuso
Leonello
L
Pitocco
Dario
D
Basso
Salvatore
S
Trové
Andrea
A
Longobardi
Anna
A
Calcagni
Maria Lucia
ML
Giordano
Alessandro
A
Ghirlanda
Giovanni
G
D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics; D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000209:etiology* / Q000503:physiopathology*; D002248:Carbon Monoxide; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications*; D005260:Female; D005541:Forced Expiratory Volume; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000000981:diagnostic imaging / Q000294:innervation*; D008297:Male; D008875:Middle Aged; D011653:Pulmonary Diffusing Capacity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012119:Respiration; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014797:Vital Capacity
D019797:3-Iodobenzylguanidine; D002248:Carbon Monoxide; D006442:Glycated Hemoglobin; D019275:Radiopharmaceuticals