Effects of hemin on heme oxygenase-1, gastric emptying, and symptoms in diabetic gastroparesis.
BACKGROUND
Therapeutic options for management of diabetic gastroparesis are limited. Failure to maintain upregulation of heme oxygenase (HO1) leads to loss of interstitial cells of Cajal and delayed gastric emptying (GE) in non-obese diabetic mice. Our hypothesis was that hemin upregulation of HO1 would restore normal GE in humans with gastroparesis.


OBJECTIVE
To compare effects of hemin and placebo infusions on HO1 activity and protein, GE, autonomic function, and gastrointestinal symptoms in diabetic gastroparesis.


METHODS
In a single-center, double-blind, placebo-controlled, randomized clinical trial, we compared intravenous hemin, prepared in albumin, or albumin alone (placebo) in 20 patients, aged 41 ± 5 (SEM) years with diabetic gastroparesis. After infusions on days 1, 3, and 7, weekly infusions were administered for 7 additional weeks. Assessments included blood tests for HO1 protein and enzyme activity levels, GE with13C-spirulina breath test, autonomic functions (baseline and end), and gastrointestinal symptoms every 2 weeks.


RESULTS
Nine of 11 patients randomized to hemin completed all study procedures. Compared to placebo, hemin increased HO1 protein on days 3 (p = 0.0002) and 7 (p = 0.008) and HO1 activity on day 3 (p = 0.0003) but not after. Gastric emptying, autonomic functions, and symptoms did not differ significantly in the hemin group relative to placebo.


CONCLUSIONS
Hemin failed to sustain increased HO1 levels beyond a week and did not improve GE or symptoms in diabetic gastroparesis. Further studies are necessary to ascertain whether more frequent hemin infusions or other drugs would have a more sustained effect on HO1 and improve GE.
Enteric Neurosciences Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA. bharucha.adil@mayo.edu.
A E
AE
Bharucha
Enteric Neurosciences Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
S L
SL
Daley
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
P A
PA
Low
Department of Physiology and Biomedical Engineering, Mayo Clinic Center for Biomedical Discovery, Rochester, MN, USA.
S J
SJ
Gibbons
Department of Physiology and Biomedical Engineering, Mayo Clinic Center for Biomedical Discovery, Rochester, MN, USA.
K M
KM
Choi
Enteric Neurosciences Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
M
M
Camilleri
Mayo Medical School, Mayo Clinic College of Medicine, Rochester, MN, USA.
J J
JJ
Saw
Enteric Neurosciences Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
G
G
Farrugia
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
A R
AR
Zinsmeister
D000328:Adult; D000368:Aged; D003920:Diabetes Mellitus / Q000097:blood* / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D018589:Gastroparesis / Q000097:blood* / Q000188:drug therapy; D051547:Heme Oxygenase-1 / Q000097:blood*; D006427:Hemin / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
D006427:Hemin; D051547:Heme Oxygenase-1
HO1; heme oxygenase; hemin; humans