Plasma levels of tumor necrosis factor-alpha, angiotensin II, growth hormone, and IGF-I are not elevated in insulin-resistant obese individuals with impaired glucose tolerance.
OBJECTIVE
To investigate the relationship between insulin resistance and plasma concentrations of free fatty acids (FFAs), leptin, and potential agonists of the insulin receptor substrate (IRS) system, including tumor necrosis factor-alpha (TNF-alpha), IGF-I, growth hormone (GH), and angiotensin II in individuals with impaired glucose tolerance (IGT).


METHODS
Because glucose toxicity per se leads to insulin resistance, the determination of the primary metabolic alterations leading to insulin resistance is best accomplished in individuals who are at an increased risk to develop type 2 diabetes. Therefore, 48 subjects with IGT and insulin resistance (IR), characterized by hyperinsulinemic-euglycemic clamps, were compared with 52 healthy insulin-sensitive (IS) control subjects with respect to the relationship between the plasma levels of TNF-alpha, IGF-I, GH, angiotensin II, FFA, leptin, and insulin resistance.


RESULTS
Between the IR and the IS groups, there were no significant differences in the plasma concentrations of TNF-alpha, GH, angiotensin II, IGF-I, and leptin. However, plasma FFA levels were significantly elevated in the IR group compared with the IS group after matching for BMI.


CONCLUSIONS
The plasma concentrations of FFA, but not TNF-alpha, IGF-I, GH, and angiotensin II, are elevated in patients at an early stage of insulin resistance, suggesting that FFAs, but not the other modulators of the IRS system, may be a primary metabolic abnormality leading to insulin resistance.
Blüher
M
M
III Medical Department, Faculty of Medicine, University of Leipzig, Germany.
Kratzsch
J
J
Paschke
R
R
D000328:Adult; D000804:Angiotensin II / Q000097:blood*; D003924:Diabetes Mellitus, Type 2; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000097:blood* / Q000150:complications; D005951:Glucose Tolerance Test; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D020738:Leptin / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D005230:Fatty Acids, Nonesterified; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I