Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity.
BACKGROUND
In obesity, insulin resistance appears frequently after activation of proinflammatory molecules. Caspase-generated cytokeratin-18 (CK-18) fragments are produced during the apoptosis of hepatic cells. The main objective in the present study is to investigate the relationship between insulin resistance and caspase-generated CK-18 fragments in patients with severe obesity.


METHODS
Sixty-two patients selected for bariatric surgery were clinically studied (sex, age, weight, waist diameter, body mass index, arterial pressure and type 2 diabetes mellitus) and analytic parameters were measured in blood (glucose concentration, cholesterol, triglycerides, insulin, glycosylated hemoglobin, aspartate aminotransferase, alanine aminotransferase, high-sensitivity C-reactive protein, adiponectin, interleukin 6, interleukin 18 and CK-18 fragments). Patient group division was based on 70th percentile of insulin resistance as measured by homeostasis model assessment (HOMA) and also according to liver histology.


RESULTS
Patients with greater insulin resistance (percentile > 70th) showed higher values of CK-18 fragments, interleukin 6 and transaminases. A positive correlation between the HOMA score, value of CK-18 fragments and triglyceride level was found. A correlation between CK-18 fragments with interleukin 6, triglycerides and transaminases was also observed. HOMA score and value of CK-18 fragments correlated with the degree of liver fibrosis.


CONCLUSIONS
Greater degree of insulin resistance induces apoptosis of hepatic cells as measured by the serum levels of CK-18 fragments.
Civera
M
M
Servicio de Endocrinología y Metabolismo, Hospital Clínico Universitario, Valencia, Spain.
Urios
A
A
Garcia-Torres
M L
ML
Ortega
J
J
Martinez-Valls
J
J
Cassinello
N
N
del Olmo
J A
JA
Ferrandez
A
A
Rodrigo
J M
JM
Montoliu
C
C
D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001786:Blood Glucose; D001794:Blood Pressure; D015992:Body Mass Index; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D020382:Interleukin-18 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D053538:Keratin-18 / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D016017:Odds Ratio; D018579:Patient Selection; D018709:Statistics, Nonparametric
D001786:Blood Glucose; D007328:Insulin; D020382:Interleukin-18; D015850:Interleukin-6; D053538:Keratin-18; D008055:Lipids