Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes

Gianluca Perseghin, Guido Lattuada, Massimo Danna, Lucia Piceni Sereni, Paola Maffi, Francesco De Cobelli, Alberto Battezzati, Antonio Secchi, Alessandro Del Maschio, Livio Luzi

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Insulin resistance is a key pathogenic factor of type 2 diabetes (T2DM); in contrast, in type 1 diabetes (T1DM) it is considered a secondary alteration. Increased intramyocellular lipid (IMCL) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM. This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM. We studied 18 patients with T1DM, 7 older and overweight/obese patients with T2DM, and 15 nondiabetic, insulin-resistant offspring of T2DM parents (OFF) and 15 healthy individuals (NOR) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6- 2H 2] glucose and 1H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 ± 0.6 and 3.2 ± 0.8 ml·kg -1·min -1) similar to OFF (5.3 ± 0.4 ml·kg -1·min -1) compared with NOR (8.5 ± 0.5 ml·kg -1·min -1 P <0.001). Soleus IMCL content was increased in T1DM (112 ± 15 AU), T2DM (108 ± 10 AU) and OFF (82 ± 13 AU) compared with NOR (52 ± 7 AU, P <0.05) and the result was inversely proportional to the MCR (R 2 = 0.27, P <0.001); an association between IMCL content and Hb A 1c was found only in T1DM (R 2 = 0.57, P <0.001). Fasting plasma adiponectin was reduced in T2DM (7 ± 1 μg/ml, P = 0.01) and OFF (11 ± 1 μg/ml, P = 0.03) but not in T1DM (25 ± 6 μg/ml), whose plasma level was increased with respect to both OFF (P = 0.03) and NOR (16 ± 2 μg/ml, P = 0.05). In conclusion, in T1DM, T2DM, and OFF, IMCL content was associated with insulin resistance, demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic (chronic hyperglycemia) alterations. The increased adiponectin levels in insulin-resistant patients with T1DM, in contrast to the reduced levels found in patients with T2DM and in OFF, demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume285
Issue number6 48-6
Publication statusPublished - Dec 2003

Fingerprint

Adiponectin
Medical problems
Type 1 Diabetes Mellitus
Insulin Resistance
Insulin
Lipids
Plasmas
Metabolic Clearance Rate
Glucose
Glucose Clamp Technique
Hyperglycemia
Magnetic resonance spectroscopy
Type 2 Diabetes Mellitus
Fasting
Magnetic Resonance Spectroscopy
Parents
Clamping devices
Muscles
Control Groups
Muscle

Keywords

  • Intramyocellular triglyceride content
  • Leptin
  • Magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes. / Perseghin, Gianluca; Lattuada, Guido; Danna, Massimo; Sereni, Lucia Piceni; Maffi, Paola; De Cobelli, Francesco; Battezzati, Alberto; Secchi, Antonio; Del Maschio, Alessandro; Luzi, Livio.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 285, No. 6 48-6, 12.2003.

Research output: Contribution to journalArticle

@article{372abb89e8fe4206aa80e9897c652eb6,
title = "Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes",
abstract = "Insulin resistance is a key pathogenic factor of type 2 diabetes (T2DM); in contrast, in type 1 diabetes (T1DM) it is considered a secondary alteration. Increased intramyocellular lipid (IMCL) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM. This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM. We studied 18 patients with T1DM, 7 older and overweight/obese patients with T2DM, and 15 nondiabetic, insulin-resistant offspring of T2DM parents (OFF) and 15 healthy individuals (NOR) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6- 2H 2] glucose and 1H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 ± 0.6 and 3.2 ± 0.8 ml·kg -1·min -1) similar to OFF (5.3 ± 0.4 ml·kg -1·min -1) compared with NOR (8.5 ± 0.5 ml·kg -1·min -1 P <0.001). Soleus IMCL content was increased in T1DM (112 ± 15 AU), T2DM (108 ± 10 AU) and OFF (82 ± 13 AU) compared with NOR (52 ± 7 AU, P <0.05) and the result was inversely proportional to the MCR (R 2 = 0.27, P <0.001); an association between IMCL content and Hb A 1c was found only in T1DM (R 2 = 0.57, P <0.001). Fasting plasma adiponectin was reduced in T2DM (7 ± 1 μg/ml, P = 0.01) and OFF (11 ± 1 μg/ml, P = 0.03) but not in T1DM (25 ± 6 μg/ml), whose plasma level was increased with respect to both OFF (P = 0.03) and NOR (16 ± 2 μg/ml, P = 0.05). In conclusion, in T1DM, T2DM, and OFF, IMCL content was associated with insulin resistance, demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic (chronic hyperglycemia) alterations. The increased adiponectin levels in insulin-resistant patients with T1DM, in contrast to the reduced levels found in patients with T2DM and in OFF, demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear.",
keywords = "Intramyocellular triglyceride content, Leptin, Magnetic resonance spectroscopy",
author = "Gianluca Perseghin and Guido Lattuada and Massimo Danna and Sereni, {Lucia Piceni} and Paola Maffi and {De Cobelli}, Francesco and Alberto Battezzati and Antonio Secchi and {Del Maschio}, Alessandro and Livio Luzi",
year = "2003",
month = "12",
language = "English",
volume = "285",
journal = "American Journal of Physiology",
issn = "0363-6119",
publisher = "American Physiological Society",
number = "6 48-6",

}

TY - JOUR

T1 - Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes

AU - Perseghin, Gianluca

AU - Lattuada, Guido

AU - Danna, Massimo

AU - Sereni, Lucia Piceni

AU - Maffi, Paola

AU - De Cobelli, Francesco

AU - Battezzati, Alberto

AU - Secchi, Antonio

AU - Del Maschio, Alessandro

AU - Luzi, Livio

PY - 2003/12

Y1 - 2003/12

N2 - Insulin resistance is a key pathogenic factor of type 2 diabetes (T2DM); in contrast, in type 1 diabetes (T1DM) it is considered a secondary alteration. Increased intramyocellular lipid (IMCL) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM. This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM. We studied 18 patients with T1DM, 7 older and overweight/obese patients with T2DM, and 15 nondiabetic, insulin-resistant offspring of T2DM parents (OFF) and 15 healthy individuals (NOR) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6- 2H 2] glucose and 1H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 ± 0.6 and 3.2 ± 0.8 ml·kg -1·min -1) similar to OFF (5.3 ± 0.4 ml·kg -1·min -1) compared with NOR (8.5 ± 0.5 ml·kg -1·min -1 P <0.001). Soleus IMCL content was increased in T1DM (112 ± 15 AU), T2DM (108 ± 10 AU) and OFF (82 ± 13 AU) compared with NOR (52 ± 7 AU, P <0.05) and the result was inversely proportional to the MCR (R 2 = 0.27, P <0.001); an association between IMCL content and Hb A 1c was found only in T1DM (R 2 = 0.57, P <0.001). Fasting plasma adiponectin was reduced in T2DM (7 ± 1 μg/ml, P = 0.01) and OFF (11 ± 1 μg/ml, P = 0.03) but not in T1DM (25 ± 6 μg/ml), whose plasma level was increased with respect to both OFF (P = 0.03) and NOR (16 ± 2 μg/ml, P = 0.05). In conclusion, in T1DM, T2DM, and OFF, IMCL content was associated with insulin resistance, demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic (chronic hyperglycemia) alterations. The increased adiponectin levels in insulin-resistant patients with T1DM, in contrast to the reduced levels found in patients with T2DM and in OFF, demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear.

AB - Insulin resistance is a key pathogenic factor of type 2 diabetes (T2DM); in contrast, in type 1 diabetes (T1DM) it is considered a secondary alteration. Increased intramyocellular lipid (IMCL) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM. This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM. We studied 18 patients with T1DM, 7 older and overweight/obese patients with T2DM, and 15 nondiabetic, insulin-resistant offspring of T2DM parents (OFF) and 15 healthy individuals (NOR) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6- 2H 2] glucose and 1H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 ± 0.6 and 3.2 ± 0.8 ml·kg -1·min -1) similar to OFF (5.3 ± 0.4 ml·kg -1·min -1) compared with NOR (8.5 ± 0.5 ml·kg -1·min -1 P <0.001). Soleus IMCL content was increased in T1DM (112 ± 15 AU), T2DM (108 ± 10 AU) and OFF (82 ± 13 AU) compared with NOR (52 ± 7 AU, P <0.05) and the result was inversely proportional to the MCR (R 2 = 0.27, P <0.001); an association between IMCL content and Hb A 1c was found only in T1DM (R 2 = 0.57, P <0.001). Fasting plasma adiponectin was reduced in T2DM (7 ± 1 μg/ml, P = 0.01) and OFF (11 ± 1 μg/ml, P = 0.03) but not in T1DM (25 ± 6 μg/ml), whose plasma level was increased with respect to both OFF (P = 0.03) and NOR (16 ± 2 μg/ml, P = 0.05). In conclusion, in T1DM, T2DM, and OFF, IMCL content was associated with insulin resistance, demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic (chronic hyperglycemia) alterations. The increased adiponectin levels in insulin-resistant patients with T1DM, in contrast to the reduced levels found in patients with T2DM and in OFF, demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear.

KW - Intramyocellular triglyceride content

KW - Leptin

KW - Magnetic resonance spectroscopy

UR - http://www.scopus.com/inward/record.url?scp=0345327627&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0345327627&partnerID=8YFLogxK

M3 - Article

VL - 285

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 6 48-6

ER -