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Cited by 339Liver Disease Diagnosis and TreatmentDiabetes, Cardiovascular Risks, and LipoproteinsPancreatic function and diabetes

Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes.

Open access
Kotronen, Anna, Juurinen, Leena, Tiikkainen, Mirja, Vehkavaara, Satu, Yki–Järvinen, Hannele·2008·Gastroenterology
DOI 10.1053/j.gastro.2008.03.021
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Abstract

Background & aims Liver fat is increased in type 2 diabetes. We determined whether it is associated with impaired insulin clearance and to what extent insulin resistance, impaired insulin clearance, or secretion contribute to fasting hyperinsulinemia. We also examined whether insulin suppression of serum free fatty acid (FFA) correlates with liver fat.Methods We compared 68 type 2 diabetic patients and age-, gender-, and body mass index (BMI)-matched nondiabetic subjects. Liver fat was determined by (1)H-MRS, body composition by magnetic resonance imaging, and insulin clearance and action on hepatic glucose production (HGP), glucose uptake, and serum FFA by the euglycemic insulin clamp technique (insulin 0.3 mU/kg x min) combined with infusion of [3-(3)H]glucose.Results Liver fat was 54% higher and insulin clearance 24% lower in type 2 diabetic patients than nondiabetic subjects. The percent suppression of both HGP and serum FFA by insulin were comparable, but serum insulin concentrations were significantly higher (34 mU/L [interquartile range, 30-39 mU/L] vs 25 mU/L [interquartile range, 22-30 mU/L]; P < .0001) in the type 2 diabetic than the nondiabetic subjects. When this difference was taken into account, both hepatic and adipose tissue insulin sensitivity were impaired in the type 2 diabetic subjects. Liver fat correlated with insulin clearance (r = -0.41; P = .001), and hepatic (r = 0.46; P = .0001) and adipose tissue (r = 0.55; P < .0001) insulin sensitivity. Hepatic but not peripheral insulin sensitivity was independently associated with liver fat content. Insulin clearance and secretion were independent determinants of fasting serum insulin.Conclusions We conclude that increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance characterize type 2 diabetic patients.

AI snapshot

Written from the paper’s full text.

TL;DR

In age-, gender-, and BMI-matched groups, type 2 diabetic patients had 54% more liver fat and 24% lower insulin clearance than nondiabetic subjects. Increased liver fat was associated with impaired insulin clearance and hepatic and adipose tissue insulin resistance, while hepatic but not peripheral insulin sensitivity was independently associated with liver fat.

Key findings

  • Liver fat was 54% higher and insulin clearance 24% lower in type 2 diabetic patients than in nondiabetic subjects; during the clamp, serum insulin was 34 mU/L (IQR, 30–39) vs 25 mU/L (IQR, 22–30), P < .0001.
  • Liver fat correlated with insulin clearance (r = −0.41; P = .001), hepatic insulin sensitivity (r = 0.46; P = .0001), and adipose tissue insulin sensitivity (r = 0.55; P < .0001).
  • When higher insulin concentrations were accounted for, hepatic and adipose tissue insulin sensitivity were impaired in type 2 diabetic patients; hepatic but not peripheral insulin sensitivity was independently associated with liver fat content.
  • Insulin clearance and secretion, but not hepatic insulin sensitivity, were independent determinants of fasting serum insulin, explaining 47% of its variation overall and 61% in type 2 diabetic patients.

Methods

  • Cross-sectional comparison of 68 total subjects: 34 type 2 diabetic patients and 34 nondiabetic subjects matched for age, gender, and BMI.
  • Liver fat was measured by 1H-MRS; body composition by MRI; insulin clearance and insulin action on hepatic glucose production, glucose uptake, and serum FFA by euglycemic hyperinsulinemic clamp (insulin 0.3 mU/kg/min) combined with [3-3H]glucose infusion.
  • Analyses used t tests, ANCOVA, Spearman correlations, and multiple linear regression, with adjustment for intraabdominal fat and fasting serum C-peptide concentrations.

Limitations

  • The paper states that dose-response studies were not performed, so it is unknown whether the insulin concentrations achieved were in the linear part of each individual’s dose-response curve for suppression of serum FFA, hepatic glucose production, and stimulation of glucose disposal.
  • The paper states that whether FFA originated from subcutaneous or visceral adipose tissue cannot be determined from the study.
  • Evident from the text: the cross-sectional design cannot establish causality; no patient underwent liver biopsy, and 5 of 68 subjects had an NAFLD fibrosis score >0.676.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1053/j.gastro.2008.03.021

Cites

66 of 66 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 41 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The percent suppression of HGP divided by the S-insulin concentration was significantly lower in type 2 diabetic patients than nondiabetic subjects.

    “The percent suppression of HGP divided by the S-insulin concentration was significantly lower in type 2 diabetic patients than nondiabetic subjects (Table 2).”
    Quote in the paperSubstantial claim
  • Findingown data

    Liver fat was 54% higher in type 2 diabetic patients than in nondiabetic subjects.

    “Intraabdominal fat was 44%, and liver fat 54%, higher in the type 2 diabetic patients than in the nondiabetic subjects.”
    • Also stated in: § Discussion · plain
      “Liver fat content was 54% higher and insulin clearance 24% lower in the type 2 diabetic patients than the nondiabetic subjects.”
    Quote in the paperSubstantial claim
  • Findingown data

    Peripheral insulin sensitivity was inversely related to liver fat in both nondiabetic subjects (r = -0.36; P = .041) and type 2 diabetic patients (r = -0.48; P = .005).

    “Peripheral insulin sensitivity was inversely related to liver fat in both nondiabetic subjects (r ϭ Ϫ0.36; P ϭ .041)and type 2 diabetic patients (r ϭ Ϫ0.48; P ϭ .005).”
    Quote in the paperSubstantial claim
  • Findingown data

    Insulin clearance was inversely related to liver fat content in both groups (r = -0.41; P = .001).

    “Insulin clearance was similarly inversely related to liver fat content in both groups (r ϭ Ϫ0.41; P ϭ .001; Figure 1).”
    Quote in the paperSubstantial claim
  • Findingown data

    Peripheral insulin sensitivity was significantly lower in type 2 diabetic patients than in nondiabetic subjects.

    “Peripheral insulin sensitivity, calculated by dividing glucose MCR during hyperinsulinemia by the S-insulin concentration during the insulin infusion, was also significantly lower in the type 2 diabetic patients than in the nondiabetic subjects.”
    Quote in the paperSubstantial claim
  • May combine two claims. 21
  • Classified as probably not a substantial claim. 11

  • May combine two claims.

    Findingown data

    In multiple linear regression analyses, both liver fat and fS-C-peptide concentrations, but neither S-FFA concentrations nor HbA1c, were independent determinants of hepatic insulin sensitivity.

    “In multiple linear regression analyses, both liver fat and fS-C-peptide concentrations, but neither S-FFA concentrations nor HbA 1c , were independent determinants of hepatic insulin sensitivity (Table 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Mean S-insulin concentrations during insulin infusion and increments in S-insulin concentrations were approximately 40%-50% higher in type 2 diabetic patients than in nondiabetic subjects.

    “Mean S-insulin concentrations during the insulin infusion and increments in S-insulin concentrations were approximately 40%-50% higher in the type 2 diabetic patients as compared with nondiabetic subjects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance characterize type 2 diabetic patients.

    “We conclude that increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance characterize type 2 diabetic patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Increased liver fat content in type 2 diabetic patients correlated with both hepatic and peripheral insulin resistance.

    “In the present study, we showed that increased liver fat content in type 2 diabetic patients correlated with both hepatic and peripheral insulin resistance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Liver fat correlates with percent suppression of S-FFA by insulin in nondiabetic subjects (r = 0.47; P = .005) and in type 2 diabetic patients (r = 0.39; P = .025).

    “Relationship between liver fat content and (A) percent suppression of S-FFA concentrations by insulin (the gray line represents the nondiabetic subjects [r ϭ 0.47; P ϭ .005],and the black line represents the type 2 diabetic patients [r ϭ 0.39; P ϭ .025].”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Both insulin clearance and fS-C-peptide concentrations, but not hepatic insulin sensitivity, remained independent determinants of fS-insulin concentrations, and explained 47% of its variation.

    “Both insulin clearance (P ϭ .002)and fS-Cpeptide concentrations (P ϭ .017),but not hepatic insulin sensitivity, remained independent determinants of fS-insulin concentrations, and explained 47% of its variation (P Ͻ .0001for ANOVA).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Both insulin clearance and secretion, but not hepatic insulin sensitivity, independently contribute to fasting insulin concentrations in type 2 diabetic patients.

    “Both insulin clearance and secretion, but not hepatic insulin sensitivity, independently contribute to fasting insulin concentrations in type 2 diabetic patients.”
    • Also stated in: § Discussion · plain
      “Insulin clearance and secretion were independent determinants of fasting serum insulin.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Increased liver fat is associated with impaired insulin clearance and hepatic and adipose tissue insulin resistance in type 2 diabetic patients.

    “In conclusion, increased liver fat is associated with impaired insulin clearance and hepatic and adipose tissue insulin resistance in type 2 diabetic patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § CLINICAL-LIVER, PANCREAS, AND BILIARY TRACT Increased Liver Fat, Impaired Insulin Clearance, and Hepatic and Adipose Tissue Insulin Resistance in Type 2 Diabetes

    Nonalcoholic fatty liver disease precedes and predicts type 2 diabetes.

    “N onalcoholic fatty liver disease (NAFLD) precedes and predicts type 2 diabetes.[1][2][3][4][5][6]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [1] Thamer, 2005, Elevated serum GGT concentrations predict reduced insulin sensitivity and increased intrahepatic lipids, Horm Metab Res source

      Not checked in the free run.

    • cites [2] Vozarova, 2002, High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes, Diabetes source

      Not checked in the free run.

    • cites [3] Perry, 1998, Prospective study of serum gamma-glutamyltransferase and risk of NIDDM, Diabetes Care source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § CLINICAL-LIVER, PANCREAS, AND BILIARY TRACT Increased Liver Fat, Impaired Insulin Clearance, and Hepatic and Adipose Tissue Insulin Resistance in Type 2 Diabetes

    Approximately 80% of endogenously secreted and 50% of intravenously infused insulin is cleared by the liver.

    “Approximately 80% of endogenously secreted and 50% of intravenously infused insulin is cleared by the liver.11”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Ferrannini, 1983, Splanchnic and renal metabolism of insulin in human subjects: a dose-response study, Am J Physiol

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The reproducibility of repeated measurements of liver fat in nondiabetic subjects studied on 2 separate occasions by the same reader in our laboratory is 11%.

    “The reproducibility of repeated measurements of liver fat in nondiabetic subjects studied on 2 separate occasions by the same reader in our laboratory is 11%.47”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Sutinen, 2002, Increased fat accumulation in the liver in HIV-infected patients with antiretroviral therapy-associated lipodystrophy, AIDS source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The type 2 diabetic patients and nondiabetic subjects were matched for age, gender, and BMI.

    “The type 2 diabetic patients and the nondiabetic subjects were matched for age, gender, and BMI.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § CLINICAL-LIVER, PANCREAS, AND BILIARY TRACT Increased Liver Fat, Impaired Insulin Clearance, and Hepatic and Adipose Tissue Insulin Resistance in Type 2 Diabetes

    Insulin clearance is decreased in obesity, particularly in abdominal obesity and advanced liver disease.

    “Insulin clearance is decreased in obesity, 12,13 particularly in abdominal obesity 14 and advanced liver disease.15”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [12] Meistas, 1983, Hyperinsulinemia of obesity is due to decreased clearance of insulin, Am J Physiol

      Not checked in the free run.

    • cites [13] Sonnenberg, 1994, Splanchnic insulin dynamics and secretion pulsatilities in abdominal obesity, Diabetes source

      Not checked in the free run.

    • cites [14] Peiris, 1986, Splanchnic insulin metabolism in obesity, J Clin Invest source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All liver spectra were analyzed by physicists who were unaware of any of the clinical data.

    “All spectra were analyzed by physicists who were unaware of any of the clinical data.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    The measurement of liver fat by proton spectroscopy has been validated against histologically determined lipid content and against estimates of fatty degeneration or infiltration by x-ray computer-assisted tomography.

    “This measurement has been validated against histologically determined lipid content 44 and against estimates of fatty degeneration or infiltration by x-ray computer-assisted tomography.38”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [44] Thomsen, 1994, Quantification of liver fat using magnetic resonance spectroscopy, Magn Reson Imaging source

      Not checked in the free run.

    • cites [38] Ryysy, 2000, Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients, Diabetes source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Metformin does not change liver fat content.

    “We have previously shown that metformin does not change liver fat content.35”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Tiikkainen, 2004, Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes, Diabetes source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § CLINICAL-LIVER, PANCREAS, AND BILIARY TRACT Increased Liver Fat, Impaired Insulin Clearance, and Hepatic and Adipose Tissue Insulin Resistance in Type 2 Diabetes

    In other studies, S-free insulin concentrations have been comparable between type 2 diabetic patients and normal subjects.

    “In other studies, S-free insulin concentrations have been comparable between type 2 diabetic patients and normal subjects.28,30 -32”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [28] Turk, 1995, The effects of non-insulin-dependent diabetes mellitus on the kinetics of onset of insulin action in hepatic and extrahepatic tissues, J Clin Invest source

      Not checked in the free run.

    • cites [30] Staehr, 2001, Assessment of hepatic insulin action in obese type 2 diabetic patients, Diabetes source

      Not checked in the free run.

    • cites [31] Basu, 2004, Insulin dose-response curves for stimulation of splanchnic glucose uptake and suppression of endogenous glucose production differ in nondiabetic humans and are abnormal in people with type 2 diabetes, Diabetes source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § CLINICAL-LIVER, PANCREAS, AND BILIARY TRACT Increased Liver Fat, Impaired Insulin Clearance, and Hepatic and Adipose Tissue Insulin Resistance in Type 2 Diabetes

    Hepatic fat accumulation is associated with impaired insulin clearance independent of obesity in nondiabetic subjects.

    “Hepatic fat accumulation is associated with impaired insulin clearance independent of obesity in nondiabetic subjects.24”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] Kotronen, 2007, Effect of liver fat on insulin clearance, Am J Physiol Endocrinol Metab source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § CLINICAL-LIVER, PANCREAS, AND BILIARY TRACT Increased Liver Fat, Impaired Insulin Clearance, and Hepatic and Adipose Tissue Insulin Resistance in Type 2 Diabetes

    In small groups of diabetic patients, insulin clearance has been reported to be normal, decreased, or even increased.

    “In small groups of diabetic patients, insulin clearance has reported to be normal, 16 -18 decreased, 19,20 or even increased.21”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [16] Polonsky, 1994, Alterations in immunoreactive proinsulin and insulin clearance induced by weight loss in NIDDM, Diabetes source

      Not checked in the free run.

    • cites [17] Gastaldelli, 2007, Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects, Gastroenterology source

      Not checked in the free run.

    • cites [18] Genuth, 1972, Metabolic clearance of insulin in man, Diabetes source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Liver fat content was inversely related to hepatic but not peripheral insulin sensitivity independent of insulin secretion, S-FFA concentrations, and HbA1c, implying that the more fat the liver contains, the more insulin resistant it is.

    “Liver fat content was inversely related to hepatic but not peripheral insulin sensitivity independent of insulin secretion, S-FFA concentrations, and HbA 1c , implying that the more fat the liver contains, the more insulin resistant it is.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The study did not perform dose-response studies and does not know whether the insulin concentrations achieved were in the linear part of every individual's dose-response curve for suppression of S-FFA, HGP, and stimulation of glucose disposal.

    “We did not perform dose-response studies and do not therefore know whether the insulin concentrations achieved were in the linear part of every individual's dose-response curve for suppression of S-FFA, HGP, and stimulation of glucose disposal.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Whether FFA originated from subcutaneous or visceral adipose tissue cannot be determined from the present study.

    “Whether FFA originated from subcutaneous or visceral adipose tissue cannot be determined from the present study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Decreased insulin clearance characterizes type 2 diabetic patients with increased liver fat and influences both fasting insulin concentrations and possibly interpretation of insulin sensitivity data.

    “This does not, however, change our main conclusion that decreased insulin clearance characterizes type 2 diabetic patients with increased liver fat and that this influences both fasting insulin concentrations and possibly interpretation of insulin sensitivity data.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Impaired insulin clearance may exacerbate hyperinsulinemia and lead to underestimation of insulin resistance.

    “The present study suggests that impaired insulin clearance may exacerbate hyperinsulinemia and lead to underestimation of insulin resistance.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The associations between liver fat and hepatic insulin resistance have previously been reported by Bajaj et al in 14 type 2 diabetic patients, and by us in nondiabetic subjects and type 2 diabetic patients treated with insulin.

    “The associations between liver fat and hepatic insulin resistance have previously been reported by Bajaj et al, 62 who studied 14 type 2 diabetic patients, and by us in nondiabetic subjects 24,39 and type 2 diabetic patients treated with insulin. 36,38”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites Bajaj et al, 62

      Not checked in the free run.

    • cites [24] Kotronen, 2007, Effect of liver fat on insulin clearance, Am J Physiol Endocrinol Metab source

      Not checked in the free run.

    • cites [39] Seppala-Lindroos, 2002, Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [36] Juurinen, 2007, Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes, Am J Physiol Endocrinol Metab source

      Not checked in the free run.

    • cites [38] Ryysy, 2000, Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients, Diabetes source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    When the difference in insulin concentrations was taken into account, the liver, peripheral, and adipose tissues were insulin resistant in type 2 diabetic subjects.

    “When this difference was taken into account, both the liver, peripheral, and adipose tissues were insulin resistant.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The type 2 diabetic and nondiabetic groups were comparable in age, BMI, percent fat, and subcutaneous fat.

    “Age (y) | 4 5 Ϯ 2 | 4 9 Ϯ 2 | N S”
    • Also stated in: § Discussion · plain
      “BMI (kg/m 2 ) | 29.9 Ϯ 0.5 | 31.6 Ϯ 0.7 | NS”
    • Also stated in: § Discussion · plain
      “% fat | 29.4 Ϯ 1.0 | 31.8 Ϯ 1.1 | NS”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Indirect estimates of insulin resistance, such as HOMA-IR and QUICKI, are derived from fasting S-insulin and glucose concentrations and have been widely used in both nondiabetic and type 2 diabetic subjects as surrogates of insulin sensitivity.

    “ndirect estimates of insulin resistance, such as HOMA-IR 63 and QUICKI, 64 are derived from fasting S-insulin and glucose concentrations and have been widely used in both nondiabetic and type 2 diabetic subjects as surrogates of insulin sensitivity.65,66”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [63] Matthews, 1985, Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man, Diabetologia source

      Not checked in the free run.

    • cites [64] Katz, 2000, Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [65] Monzillo, 2003, Evaluation of insulin sensitivity in clinical practice and in research settings, Nutr Rev source

      Not checked in the free run.

    • cites [66] Wallace, 2004, Use and abuse of HOMA modeling, Diabetes Care source

      Not checked in the free run.

28 of 28

  • The authors state this as an assumption.

    Impaired insulin suppression of FFA reflects FFA flux from adipose tissue rather than impaired uptake of FFA.

    “This assumes that impaired insulin suppression of FFA reflects FFA flux from adipose tissue rather than impaired uptake of FFA.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Fatty acid-induced reductions in insulin receptor number and function in the liver may also reduce hepatic insulin clearance, causing systemic hyperinsulinemia, itself a contributor to both insulin resistance and reduced mitochondrial function.

    “Fatty acid-induced reductions in insulin receptor number and function in the liver (211) may also reduce hepatic insulin clearance (226), causing systemic hyperinsulinemia, itself a contributor to both insulin resistance and reduced mitochondrial function (214,227,228).”

    From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [214]

  • Hepatic lipid accumulation is associated with obesity in humans, particularly central (abdominal) in location, and in parallel with low adiponectin levels.

    “Although the relative roles of each of these possibilities is incompletely understood, hepatic lipid accumulation is associated with obesity in humans, particularly central (abdominal) in location (214, 215), and in parallel with low adiponectin levels (216).”

    From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [214]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Abstract states 68 diabetic patients, but Table 1 lists 34

    Minor

    The abstract describes 68 type 2 diabetic patients plus matched nondiabetic subjects. Table 1 instead lists 34 diabetic patients and 34 nondiabetic subjects, for 68 participants in total.

  • Adipose sensitivity and resistance are both reported to increase with liver fat

    Minor

    Figure 3 reports a positive correlation between liver fat and adipose tissue insulin sensitivity. The Discussion instead says adipose tissue insulin resistance is positively correlated with liver fat, reversing the direction of the reported relationship.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Ohlson, 1988, Risk factors for type 2 (non-insulin-dependent) diabetes mellitus, Diabetologia, 31, 798

Cited by

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Related

Authors
Kotronen, A., Juurinen, L., Tiikkainen, M., Vehkavaara, S., & Yki–Järvinen, H.
Affiliations
University of Helsinki (FI)
Corresponding author
Kotronen, Anna
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2008-07
Volume
135
Issue
1
Pages
122-130
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2008.03.021
OpenAlex
W2067507037
Semantic Scholar
06aff141dee9cdd7a2d61b4ec30f46283d160cf9
Cited by
339
References
66
Citations by year
2026: 9 · 2025: 8 · 2024: 15 · 2023: 19 · 2022: 20 · 2021: 29 · 2020: 24 · 2019: 23 · 2018: 18 · 2017: 22 · 2016: 20 · 2015: 20 · 2014: 24 · 2013: 21 · 2012: 12
FWCI
13.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Novo Nordisk Fonden
  • Academy of Finland
  • Sixth Framework Programme (LSHM-CT-2005-018734)
  • European Commission
  • Sigrid Juséliuksen Säätiö
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
type 2 diabetes, hepatic steatosis, liver fat, insulin clearance, insulin resistance, hepatic insulin sensitivity, adipose tissue insulin sensitivity, fasting hyperinsulinemia, hepatic glucose production, free fatty acids, insulin secretion, hepatic glucose uptake
MeSH terms
Adipose Tissue, Adult, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Fatty Liver, Female, Humans, Hyperinsulinism, Insulin, Insulin Resistance, Liver, Magnetic Resonance Imaging, Male, Middle Aged, Protons, Regression Analysis, Glucose Clamp Technique, Body Mass Index, Multivariate Analysis

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