Postabsorptive and insulin-stimulated energy and protein metabolism in patients with myotonic dystrophy type 1.
BACKGROUND
Exaggerated insulin resistance was described as the major metabolic abnormality in myotonic dystrophy type 1 (DM1). We reported recently that the severity of the impairment in insulin-stimulated glucose metabolism in these patients was overestimated.


OBJECTIVE
The aim was to dissect out insulin action with respect to whole-body energy homeostasis and glucose, protein, and lipid metabolism in patients with DM1 to assess the relevance of insulin resistance to the heterogeneous clinical manifestations of this syndrome.


METHODS
Ten nondiabetic patients with DM1 and 10 matched healthy control subjects were studied by means of 1) dual-energy X-ray absorptiometry; 2) a euglycemic-hyperinsulinemic clamp (40 mU. m(-2). min(-1)) combined with a primed, continuous infusion of [6,6-d(2)]glucose and [1-(13)C]leucine; 3) indirect calorimetry; and 4) localized (1)H magnetic resonance spectroscopy of the calf muscles.


RESULTS
Patients with DM1 had less lean body mass, greater fat mass, and greater intramyocellular lipid contents than did healthy control subjects. Energy expenditure and glucose and lipid metabolism did not differ significantly between the groups. In contrast, markers of proteolysis were higher in DM1 patients in the postabsorptive and insulin-stimulated conditions and were associated with lower plasma concentrations of insulin-like growth factor 1 (P < 0.03) and higher plasma concentrations of tumor necrosis factor alpha receptor 2 (P = 0.04).


CONCLUSIONS
Despite greater body fat and intramyocellular lipid contents in patients with DM1, insulin sensitivity was not significantly different between patients and control subjects. In contrast, the loss of lean body mass in patients with DM1 was associated with abnormal postabsorptive and insulin-stimulated regulation of protein breakdown. Lower plasma insulin-like growth factor 1 concentrations and higher tumor necrosis factor system activity might be involved in the muscle wasting of DM1.
Perseghin
Gianluca
G
Internal Medicine Section of Nutrition/Metabolism, Università Vita e Salute San Raffaele, Istituto Scientifico H San Raffaele, via Olgettina 60, 20132 Milan, Italy. perseghin.gianluca@hsr.it
Comola
Mauro
M
Scifo
Paola
P
Benedini
Stefano
S
De Cobelli
Francesco
F
Lanzi
Roberto
R
Costantino
Federica
F
Lattuada
Guido
G
Battezzati
Alberto
A
Del Maschio
Alessandro
A
Luzi
Livio
L
D015502:Absorptiometry, Photon; D000328:Adult; D001823:Body Composition; D002153:Calorimetry, Indirect; D016022:Case-Control Studies; D004734:Energy Metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood*; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009223:Myotonic Dystrophy / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*
D007328:Insulin; D011506:Proteins; D005947:Glucose