Postabsorptive and insulin-stimulated energy and protein metabolism in patients with myotonic dystrophy type 1

Gianluca Perseghin, Mauro Comola, Paola Scifo, Stefano Benedini, Francesco De Cobelli, Roberto Lanzi, Federica Costantino, Guido Lattuada, Alberto Battezzati, Alessandro Del Maschio, Livio Luzi

Research output: Contribution to journalArticle

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Abstract

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. Design: 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 mil·m-2·tmin -1) combined with a primed, continuous infusion of [6,6-d 2]glucose and [1-13C]leucine; J) indirect calorimetry; and 4) localized 1H 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 a 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.

Original languageEnglish
Pages (from-to)357-364
Number of pages8
JournalAmerican Journal of Clinical Nutrition
Volume80
Issue number2
Publication statusPublished - Aug 2004

Fingerprint

Myotonic Dystrophy
protein metabolism
energy metabolism
Energy Metabolism
insulin
Insulin
Proteins
insulin resistance
Insulin Resistance
Glucose
glucose
lean body mass
somatomedins
Somatomedins
Lipid Metabolism
lipid metabolism
Healthy Volunteers
lipid content
Receptors, Tumor Necrosis Factor, Type II
Lipids

Keywords

  • H magnetic resonance spectroscopy
  • Fatty acid metabolism
  • Indirect calorimetry
  • Insulin sensitivity
  • Intramyocellular lipid content
  • Leucine metabolism

ASJC Scopus subject areas

  • Food Science
  • Medicine (miscellaneous)

Cite this

Postabsorptive and insulin-stimulated energy and protein metabolism in patients with myotonic dystrophy type 1. / Perseghin, Gianluca; Comola, Mauro; Scifo, Paola; Benedini, Stefano; De Cobelli, Francesco; Lanzi, Roberto; Costantino, Federica; Lattuada, Guido; Battezzati, Alberto; Del Maschio, Alessandro; Luzi, Livio.

In: American Journal of Clinical Nutrition, Vol. 80, No. 2, 08.2004, p. 357-364.

Research output: Contribution to journalArticle

Perseghin, Gianluca ; Comola, Mauro ; Scifo, Paola ; Benedini, Stefano ; De Cobelli, Francesco ; Lanzi, Roberto ; Costantino, Federica ; Lattuada, Guido ; Battezzati, Alberto ; Del Maschio, Alessandro ; Luzi, Livio. / Postabsorptive and insulin-stimulated energy and protein metabolism in patients with myotonic dystrophy type 1. In: American Journal of Clinical Nutrition. 2004 ; Vol. 80, No. 2. pp. 357-364.
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abstract = "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. Design: 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 mil·m-2·tmin -1) combined with a primed, continuous infusion of [6,6-d 2]glucose and [1-13C]leucine; J) indirect calorimetry; and 4) localized 1H 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 a 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.",
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AU - Benedini, Stefano

AU - De Cobelli, Francesco

AU - Lanzi, Roberto

AU - Costantino, Federica

AU - Lattuada, Guido

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AU - Del Maschio, Alessandro

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