Reduced whole-body lipid oxidation is associated with insulin resistance, but not with intramyocellular lipid content in offspring of type 2 diabetic patients.
OBJECTIVE
Intramyocellular lipid accumulation and insulin resistance are thought to be due to reduced lipid oxidation in a human model of high risk of developing type 2 diabetes.


METHODS
We studied 32 offspring of type 2 diabetic parents and 32 control individuals by means of DXA, indirect calorimetry, insulin clamp and 1H MRS of the calf muscles, and differences between and within study groups were analysed before and after segregation by quartiles of fasting lipid oxidation.


RESULTS
In comparison with control subjects, the offspring showed impaired insulin sensitivity, which was associated with higher fasting intramyocellular lipid content (Spearman's rho -0.35; p=0.04), but fasting lipid oxidation did not differ between groups (1.21+/-0.46 vs. 1.25+/-0.37 mg.kg(-1) lean body mass per min; p=0.70). Nevertheless, offspring in the lowest quartile of lipid oxidation had the most severe impairment of insulin sensitivity and a strong association was shown between lipid oxidation and insulin sensitivity within quartiles (Spearman's rho 0.47; p=0.01); this was not observed within the control group (Spearman's rho 0.13; p=0.47). Intramyocellular lipid content was not significantly different within quartiles of lipid oxidation in either of the groups.


CONCLUSIONS
Insulin sensitivity improved across increasing quartiles of fasting lipid oxidation in the offspring group, but remained constant in the control group, supporting the hypothesis that impaired fat oxidation is a primary pathogenic factor of insulin resistance in people with a genetic background for type 2 diabetes. Despite their association with impaired insulin sensitivity, soleus and tibialis anterior intramyocellular lipid content remained constant across increasing quartiles of fasting lipid oxidation within both groups.
Lattuada
G
G
Internal Medicine-Section of Nutrition/Metabolism, Scientific Institute H San Raffaele, via Olgettina 60, 20132 Milan, Italy.
Costantino
F
F
Caumo
A
A
Scifo
P
P
Ragogna
F
F
De Cobelli
F
F
Del Maschio
A
A
Luzi
L
L
Perseghin
G
G
D052242:Adiponectin; D000328:Adult; D032721:Adult Children; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005215:Fasting / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000737:chemistry*; D010084:Oxidation-Reduction; D010290:Parents
D052242:Adiponectin; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D008055:Lipids; D002784:Cholesterol; D005947:Glucose