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Liver Fat Content and Hepatic Insulin Sensitivity in Overweight Patients With Type 1 Diabetes

Llaurado, Gemma; Sevastianova, Ksenia; Sadevirta, Sanja; Hakkarainen, Antti; Lundbom, Nina; Orho-Melander, Marju LU ; Groop, Per-Henrik; Forsblom, Carol and Yki-Jarvinen, Hannele (2015) In Journal of Clinical Endocrinology and Metabolism 100(2). p.607-616
Abstract
Objectives: Patients with type 1 diabetes mellitus (T1DM) lack the portal/peripheral insulin gradient, which might diminish insulin stimulation of hepatic lipogenesis and protect against development of nonalcoholic fatty liver disease (NAFLD). We compared liver fat content and insulin sensitivity of hepatic glucose production and lipolysis between overweight T1DM patients and nondiabetic subjects. Materials and Methods: We compared 32 overweight adult T1DM patients and 32 nondiabetic subjects matched for age, body mass index (BMI), and gender. Liver fat content was measured using proton magnetic resonance spectroscopy (H-1-MRS), body composition by magnetic resonance imaging, and insulin sensitivity using the euglycemic-hyperinsulinemic... (More)
Objectives: Patients with type 1 diabetes mellitus (T1DM) lack the portal/peripheral insulin gradient, which might diminish insulin stimulation of hepatic lipogenesis and protect against development of nonalcoholic fatty liver disease (NAFLD). We compared liver fat content and insulin sensitivity of hepatic glucose production and lipolysis between overweight T1DM patients and nondiabetic subjects. Materials and Methods: We compared 32 overweight adult T1DM patients and 32 nondiabetic subjects matched for age, body mass index (BMI), and gender. Liver fat content was measured using proton magnetic resonance spectroscopy (H-1-MRS), body composition by magnetic resonance imaging, and insulin sensitivity using the euglycemic-hyperinsulinemic clamp technique (insulin 0.4 mU/kg.min combined with infusion of D-[3-H-3] glucose). We also hypothesized that low liver fat might protect from obesity-associated increases in insulin requirements and, therefore, determined insulin requirements across BMI categories in 3164 T1DM patients. Results: Liver fat content was significantly lower in T1DM patients than in nondiabetic subjects (0.6% [25th-75th quartiles, 0.3%-1.1%] vs 9.0% [ 3.0%-18.0%]; P<.001). The endogenous rate of glucose production (R-a) during euglycemic hyperinsulinemia was significantly lower (0.4 [-0.7 to 0.8] mg/kg fat-free mass.min vs 0.9 [0.2-1.6] fat-free mass.min; P=.012) and the percent suppression of endogenous R-a by insulin was significantly greater (89% [78%-112%] vs 77% [50%-94%]; p=.009) in T1DM patients than in nondiabetic subjects. Serum nonesterified fatty acid concentrations during euglycemic hyperinsulinemia were significantly lower (78.5 [33.0-155.0] vs 306 [200.0-438.0] mu mol/L; P<.001) and the percent suppression of nonesterified fatty acids significantly higher (89.1% [78.6%-93.3%] vs 51.4% [36.5%-71.1%]; P<.001) in T1DM patients than in nondiabetic subjects. Insulin doses were similar across BMI categories. Conclusions: T1DM patients might be protected from steatosis and hepatic insulin resistance. Obesity may not increase insulin requirements in T1DM. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
100
issue
2
pages
607 - 616
publisher
The Endocrine Society
external identifiers
  • wos:000353350900066
  • scopus:84922576094
ISSN
1945-7197
DOI
10.1210/jc.2014-3050
language
English
LU publication?
yes
id
f16e7ab9-abf8-4c8c-bdc5-2970b411ca7e (old id 5401157)
date added to LUP
2015-06-01 09:24:37
date last changed
2017-10-22 04:22:19
@article{f16e7ab9-abf8-4c8c-bdc5-2970b411ca7e,
  abstract     = {Objectives: Patients with type 1 diabetes mellitus (T1DM) lack the portal/peripheral insulin gradient, which might diminish insulin stimulation of hepatic lipogenesis and protect against development of nonalcoholic fatty liver disease (NAFLD). We compared liver fat content and insulin sensitivity of hepatic glucose production and lipolysis between overweight T1DM patients and nondiabetic subjects. Materials and Methods: We compared 32 overweight adult T1DM patients and 32 nondiabetic subjects matched for age, body mass index (BMI), and gender. Liver fat content was measured using proton magnetic resonance spectroscopy (H-1-MRS), body composition by magnetic resonance imaging, and insulin sensitivity using the euglycemic-hyperinsulinemic clamp technique (insulin 0.4 mU/kg.min combined with infusion of D-[3-H-3] glucose). We also hypothesized that low liver fat might protect from obesity-associated increases in insulin requirements and, therefore, determined insulin requirements across BMI categories in 3164 T1DM patients. Results: Liver fat content was significantly lower in T1DM patients than in nondiabetic subjects (0.6% [25th-75th quartiles, 0.3%-1.1%] vs 9.0% [ 3.0%-18.0%]; P&lt;.001). The endogenous rate of glucose production (R-a) during euglycemic hyperinsulinemia was significantly lower (0.4 [-0.7 to 0.8] mg/kg fat-free mass.min vs 0.9 [0.2-1.6] fat-free mass.min; P=.012) and the percent suppression of endogenous R-a by insulin was significantly greater (89% [78%-112%] vs 77% [50%-94%]; p=.009) in T1DM patients than in nondiabetic subjects. Serum nonesterified fatty acid concentrations during euglycemic hyperinsulinemia were significantly lower (78.5 [33.0-155.0] vs 306 [200.0-438.0] mu mol/L; P&lt;.001) and the percent suppression of nonesterified fatty acids significantly higher (89.1% [78.6%-93.3%] vs 51.4% [36.5%-71.1%]; P&lt;.001) in T1DM patients than in nondiabetic subjects. Insulin doses were similar across BMI categories. Conclusions: T1DM patients might be protected from steatosis and hepatic insulin resistance. Obesity may not increase insulin requirements in T1DM.},
  author       = {Llaurado, Gemma and Sevastianova, Ksenia and Sadevirta, Sanja and Hakkarainen, Antti and Lundbom, Nina and Orho-Melander, Marju and Groop, Per-Henrik and Forsblom, Carol and Yki-Jarvinen, Hannele},
  issn         = {1945-7197},
  language     = {eng},
  number       = {2},
  pages        = {607--616},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Liver Fat Content and Hepatic Insulin Sensitivity in Overweight Patients With Type 1 Diabetes},
  url          = {http://dx.doi.org/10.1210/jc.2014-3050},
  volume       = {100},
  year         = {2015},
}