title: Insulin resistance causes human gallbladder dysmotility.
abstract: Obesity, diabetes, and hyperlipidemia are known risk factors for the development of gallstones. A growing body of animal and human data has correlated insulin resistance with organ dysfunction. The relationship among obesity, diabetes, hyperlipidemia, and abnormal gallbladder motility remains unclear. Therefore, we designed a study to investigate the association among obesity, insulin resistance, hyperlipidemia, and gallbladder dysmotility. One hundred ninety-two healthy adult nondiabetic volunteers were studied. Gallbladder ultrasounds were performed before and after a standardized fatty meal. A gallbladder ejection fraction (EF) was calculated, and an EF of < 25% was considered abnormal. Serum was analyzed for cholesterol, triglycerides, cholecystokinin, leptin, glucose, and insulin. The homeostasis assessment model (HOMA) was used to determine insulin resistance. The volunteers had a mean age of 38 years (range, 18-77), and 55% were female. Thirty subjects (15%) had gallstones and were excluded from the study. Thirty subjects (19%) had abnormal gallbladder motility (EF < 25%). In lean subjects (n = 96) fasting glucose was significantly increased in the 16 subjects with gallbladder EF < 25% versus the 80 subjects with gallbladder EF > 25% (109 +/- 20 mg/dl versus 78 +/- 2 mg/dl, P < 0.05). Similarly, the HOMA index was significantly greater in subjects with gallbladder EF < 25% versus gallbladder EF >25% (3.3 +/- 1.2 versus 2.0 +/- 0.2, P < 0.05). In obese subjects (n = 66), fasting glucose, insulin, and insulin resistance were not associated with a gallbladder EF < 25%. These data suggest that in lean, nondiabetic volunteers without gallstones, gallbladder dysmotility is associated with an elevated fasting glucose as well as a high index of insulin resistance. We conclude that insulin resistance alone may be responsible for gallbladder dysmotility that may result in acalculous cholecystitis or gallstone formation.
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. anakeeb@iupui.edu
authors.forename: Attila
authors.initials: A
authors.lastname: Nakeeb
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.forename: Hayder
authors.initials: H
authors.lastname: Al-Azzawi
authors.forename: Gabriele E
authors.initials: GE
authors.lastname: Sonnenberg
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Kissebah
authors.forename: Henry A
authors.initials: HA
authors.lastname: Pitt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001786:Blood Glucose; D015992:Body Mass Index; D002766:Cholecystokinin / Q000097:blood; D005260:Female; D005704:Gallbladder / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005705:Gallbladder Diseases / Q000209:etiology*; D016473:Gallbladder Emptying; D006801:Humans; D006949:Hyperlipidemias; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D015146:Midwestern United States; D009765:Obesity / Q000503:physiopathology*; D014463:Ultrasonography; D044465:White People
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D002766:Cholecystokinin