The DOI matches its Crossref record; 39 of the 40 references it cites were found in a registry or an index.
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.
Open accessAbstract
To determine causes of interindividual variation in insulin requirements, we recruited 20 type 2 diabetic patients with stable glucose control and insulin doses for >1 year on combination therapy with bedtime NPH insulin and metformin. Insulin absorption (increase in free and total insulin over 8 h after a subcutaneous dose of regular insulin) and actions of intravenous (6-h 0.3 mU x kg(-1) x min(-1) euglycemic insulin clamp combined with [3-3H]glucose) and subcutaneous (glucose infusion rate required to maintain isoglycemia and suppression of free fatty acids [FFAs]) insulin, liver fat content (proton spectroscopy), visceral fat (magnetic resonance imaging), weight, and body composition were determined. We found the following variation in parameters: insulin dose range 10-176 U (mean 42 U, fold variation 17.6x) or 0.13-1.39 U/kg (0.44 U/kg, 10.7x), absorbed insulin 10.6x, action of subcutaneous insulin to suppress FFAs 7.5 x and to stimulate glucose metabolism (M value) 11.5x, body weight 67-127 kg (91 kg, 1.9x), liver fat 2-28% (12%, 14x), and visceral fat 179-2,053 ml (1,114 ml, 11.5x). The amount of insulin absorbed, measured as either free or total insulin, was significantly correlated with its ability to suppress FFAs and stimulate glucose metabolism but not with the insulin dose per se. The actions of absorbed insulin were, on the other hand, significantly correlated with the daily insulin dose (r = 0.70 for action on FFAs, P < 0.001, and r = -0.61 for M value, P < 0.005). Actions of subcutaneous and intravenous insulin to suppress FFAs were significantly correlated (r = 0.82, P < 0.001, R2 = 67%). Of the measures of adiposity, the percent hepatic fat was the parameter best correlated with the daily insulin dose (r = 0.76, P < 0.001). The percent hepatic fat was also significantly correlated with the ability of intravenous insulin to suppress endogenous glucose production (r = 0.72, P < 0.005). We conclude that the major reason for interindividual variation in insulin requirements in type 2 diabetes is the variation in insulin action. Variation in hepatic fat content may influence insulin requirements via an effect on the sensitivity of endogenous glucose production to insulin.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Previous studies by our group (9, 17-20) and others (7, 21, 22) have demonstrated a strong relationship between triglyceride content in liver and muscle and insulin resistance in these tissues.”
From Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy (2002) · cites this paper as [22]
Experimental — accuracy not yet measuredIn the citing paper
“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”
From Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. (2008) · cites this paper as [38]
In the citing paper
“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”
From Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. (2008) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425
Desbuquois, B., & Aurbach, G. D. (1971) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-33-5-732 · Cited by 1,295
Lillioja, S., Young, A. A., Culter, C. L., Ivy, J. L., Abbott, W. G., Zawadzki, J. K., Yki-Järvinen, H., Christin, L., Secomb, T. W., & Bogardus, C. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113088 · Cited by 782
Self-citationA New and Rapid Method for the Determination of Glucose by Measurement of Rate of Oxygen Consumption
Kadish, A. H., Litle, R. L., & Sternberg, J. (1968) · Clinical Chemistry · doi:10.1093/clinchem/14.2.116 · Cited by 739
Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo
Szczepaniak, L. S., Babcock, E. E., Schick, F., Dobbins, R. L., Garg, A., Burns, D. K., McGarry, J. D., & Stein, D. T. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.5.e977 · Cited by 688
Liver Pathology and the Metabolic Syndrome X in Severe Obesity
Marceau, P., Biron, S., Hould, F. S., Marceau, S., Simard, S., Thung, S. N., & Kral, J. G. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.5.5661 · Cited by 633
Determination of Free and Total Insulin and C-Peptide in Insulin-treated Diabetics
Kuzuya, H., BLIX, P. M., Horwitz, D. L., Steiner, D. F., & Rubenstein, A. H. (1977) · Diabetes · doi:10.2337/diab.26.1.22 · Cited by 603
Yki-Järvinen, H., Ryysy, L., Nikkilä, K., Tulokas, T., Vanamo, R., & Heikkilä, M. (1999) · Annals of Internal Medicine · doi:10.7326/0003-4819-130-5-199903020-00002 · Cited by 433
Self-citationQuantification of liver fat using magnetic resonance spectroscopy
Thomsen, C., Becker, U., Winkler, K., Christoffersen, P., Jensen, M., & Henriksen, O. (1994) · Magnetic Resonance Imaging · doi:10.1016/0730-725x(94)92543-7 · Cited by 332
A microfluorometric method for the determination of free fatty acids in plasma
Miles, J., Glasscock, R., Aikens, J., Gerich, J. E., & Haymond, M. W. (1983) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38029-9 · Cited by 329
Research works printed but not linked: 1
- Gidez LJ, Miller GJ, Burstein M, Eder HA: Analysis of plasma high density lipoprotein subclasses by a precipitation procedure: correlation with prepar- ative and analytical ultracentrifugation. In High Density Lipoprotein Method- ology Workshop, San Francisco, 1979.
Cited by
Sorted by citations
Simental‐Mendía, L. E., Rodríguez‐Morán, M., & Guerrero‐Romero, F. (2008) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2008.0034 · Cited by 2,581
Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB
Cai, D., Yuan, M., Frantz, D. F., Melendez, P. A., Hansen, L., Lee, J., & Shoelson, S. E. (2005) · Nature Medicine · doi:10.1038/nm1166 · Cited by 2,245
Yki-Järvinen, H. (2004) · New England Journal of Medicine · doi:10.1056/nejmra041001 · Cited by 1,830
Self-citationProgression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis
Anstee, Q. M., Targher, G., & Day, C. P. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.41 · Cited by 1,747
Pathogenesis of type 2 diabetes mellitus
DeFronzo, R. A. (2004) · Medical Clinics of North America · doi:10.1016/j.mcna.2004.04.013 · Cited by 1,342
Metadata
- Authors
- Ryysy, L., Häkkinen, A. M., Goto, T., Vehkavaara, S., Westerbacka, J., Halavaara, J., & Yki-Järvinen, H.
- Affiliations
- University of Helsinki (FI)
- Department of Medicine, University of Helsinki, Finland.
- ORCID
- Goto, T
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2000-05-01
- Volume
- 49
- Issue
- 5
- Pages
- 749-758
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2132477505
- Cited by
- 431
- References
- 40
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 10 · 2022: 9 · 2021: 11 · 2020: 13 · 2019: 10 · 2018: 8 · 2017: 19 · 2016: 9 · 2015: 11 · 2014: 21 · 2013: 25 · 2012: 13
- FWCI
- 13.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes, insulin requirement, insulin absorption, hepatic fat content, free fatty acids, insulin action, glucose metabolism, insulin resistance, visceral fat, adiposity, interindividual variability, insulin dose adjustment, metformin, NPH insulin, hepatic steatosis, hepatic insulin sensitivity, hepatic insulin secretion, hepatic insulin clearance
- MeSH terms
- Absorption, Adipose Tissue, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Fatty Acids, Nonesterified, Female, Glucose, Humans, Hypoglycemic Agents, Injections, Intravenous, Injections, Subcutaneous, Insulin, Liver, Male, Middle Aged
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
