Postabsorptive and insulin-stimulated energy homeostasis and leucine turnover in offspring of type 2 diabetic patients.
OBJECTIVE
This study was performed to ascertain whether insulin resistance with respect to protein metabolism is an additional primary metabolic abnormality affecting insulin-resistant offspring of type 2 diabetic parents, along with insulin resistance with respect to glucose and lipid metabolism.


METHODS
We studied 18 young, nonobese offspring of type 2 diabetic parents and 27 healthy matched (by means of dual-energy X-ray absorption) individuals with the bolus plus continuous infusion of [6,6-(2)H(2)]glucose and [1-(13)C]leucine in combination with the insulin clamp (40 mU x m(-2) x min(-1)).


RESULTS
Fasting plasma leucine, phenylalanine, alanine, and glutamine concentrations, as well as the glucose and leucine turnover (reciprocal pool model: 155 +/- 10 vs. 165 +/- 5 micromol x kg lean body mass(-1) x h(-1) in offspring of type 2 diabetic patients and healthy matched individuals, respectively), were also not different. During the clamp, glucose turnover rates were significantly reduced in offspring of type 2 diabetic patients (7.1 +/- 0.5) in comparison with healthy matched individuals (9.9 +/- 0.6 mg x kg lean body mass(-1) x min(-1); P < 0.01). Also, the suppression of leucine turnover was impaired in offspring of type 2 diabetic patients (12 +/- 1%) in comparison with healthy matched individuals (17 +/- 1%; P = 0.04) and correlated with the degree of the impairment of insulin-stimulated glucose metabolism (R(2) = 0.13; P = 0.02).


CONCLUSIONS
Nonobese, nondiabetic, insulin-resistant offspring of type 2 diabetic patients were characterized by an impairment of insulin-dependent suppression of protein breakdown, which was proportional to the impairment of glucose metabolism. These results demonstrate that in humans, a primary in vivo impairment of insulin action affects glucose and fatty acid metabolism as previously shown and also protein/amino acid metabolism.
Lattuada
Guido
G
Istituto Scientifico H San Raffaele, Internal Medicine, Section of Nutrition/Metabolism & Unit of Clinical Spectroscopy via Olgettina 60, 20132, Milan, Italy.
Sereni
Lucia Piceni
LP
Ruggieri
Dora
D
Scollo
Antonella
A
Benedini
Stefano
S
Ragogna
Francesca
F
Costantino
Federica
F
Battezzati
Alberto
A
Luzi
Livio
L
Perseghin
Gianluca
G
D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism*; D008297:Male; D019518:Postprandial Period
D007004:Hypoglycemic Agents; D007328:Insulin; D007930:Leucine; D005947:Glucose