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Cited by 431Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

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.

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Ryysy, L, Häkkinen, A M, Goto, T, Vehkavaara, S, Westerbacka, J, Halavaara, J, Yki-Järvinen, H·2000·Diabetes
DOI 10.2337/diabetes.49.5.749
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Abstract

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.

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  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.

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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
DOI
10.2337/diabetes.49.5.749
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
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

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