Increased glucose effectiveness in normoglycemic but insulin-resistant relatives of patients with non-insulin-dependent diabetes mellitus. A novel compensatory mechanism - PubMed (original) (raw)
Comparative Study
. 1994 Sep;94(3):1196-204.
doi: 10.1172/JCI117436.
Affiliations
- PMID: 8083360
- PMCID: PMC295197
- DOI: 10.1172/JCI117436
Comparative Study
Increased glucose effectiveness in normoglycemic but insulin-resistant relatives of patients with non-insulin-dependent diabetes mellitus. A novel compensatory mechanism
J E Henriksen et al. J Clin Invest. 1994 Sep.
Abstract
20 normoglycemic first degree relatives of non-insulin-dependent diabetes mellitus (NIDDM) patients were compared with 20 matched subjects without any family history of diabetes using the intravenous glucose tolerance test with minimal model analysis of glucose disappearance and insulin kinetics. Intravenous glucose tolerance index (Kg) was similar in both groups (1.60 +/- 0.14 vs 1.59 +/- 0.18, x 10(-2) min-1, NS). However, insulin sensitivity (Si) was reduced (3.49 +/- 0.43 vs 4.80 +/- 0.61, x 10(-4) min-1 per mU/liter, P = 0.05), whereas glucose effectiveness (Sg) was increased (1.93 +/- 0.14 vs 1.52 +/- 0.16, x 10(-2) min-1, P < 0.05) in the relatives. Despite insulin resistance neither fasting plasma insulin concentration (7.63 +/- 0.48 vs 6.88 +/- 0.45, mU/liter, NS) nor first phase insulin responsiveness (Phi1) (3.56 +/- 0.53 vs 4.13 +/- 0.62, mU/liter min-1 per mg/dl, NS) were increased in the relatives. Phi1 was reduced for the degree of insulin resistance in the relatives so that the Phi1 x Si index was lower in the relatives (11.5 +/- 2.2 vs 16.7 +/- 2.0, x 10(-4) min-2 per mg/dl, P < 0.05). Importantly, glucose effectiveness correlated with Kg and with basal glucose oxidation but not with total glucose transporter 4 (GLUT4) content in a basal muscle biopsy. In conclusion we confirm the presence of insulin resistance in first degree relatives of NIDDM patients. However, insulin secretion was altered and reduced for the degree of insulin resistance in the relatives, whereas glucose effectiveness was increased. We hypothesize that increased glucose effectiveness maintains glucose tolerance within normal limits in these "normoinsulinemic" relatives of NIDDM patients.
Similar articles
- Glucose-mediated glucose disposal in insulin-resistant normoglycemic relatives of type 2 diabetic patients.
Henriksen JE, Levin K, Thye-Rønn P, Alford F, Hother-Nielsen O, Holst JJ, Beck-Nielsen H. Henriksen JE, et al. Diabetes. 2000 Jul;49(7):1209-18. doi: 10.2337/diabetes.49.7.1209. Diabetes. 2000. PMID: 10909980 - Risk and mechanism of dexamethasone-induced deterioration of glucose tolerance in non-diabetic first-degree relatives of NIDDM patients.
Henriksen JE, Alford F, Ward GM, Beck-Nielsen H. Henriksen JE, et al. Diabetologia. 1997 Dec;40(12):1439-48. doi: 10.1007/s001250050847. Diabetologia. 1997. PMID: 9447952 - Toward an integrated phenotype in pre-NIDDM.
Bergman RN, Watanabe R, Rebrin K, Ader M, Steil G. Bergman RN, et al. Diabet Med. 1996 Sep;13(9 Suppl 6):S67-77. Diabet Med. 1996. PMID: 8894486 Review. - Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach.
Bergman RN. Bergman RN. Diabetes. 1989 Dec;38(12):1512-27. doi: 10.2337/diab.38.12.1512. Diabetes. 1989. PMID: 2684710 Review.
Cited by
- A novel splice-affecting HNF1A variant with large population impact on diabetes in Greenland.
Thuesen ACB, Stæger FF, Kaci A, Solheim MH, Aukrust I, Jørsboe E, Santander CG, Andersen MK, Li Z, Gilly A, Stinson SE, Gjesing AP, Bjerregaard P, Pedersen ML, Larsen CVL, Grarup N, Jørgensen ME, Zeggini E, Bjørkhaug L, Njølstad PR, Albrechtsen A, Moltke I, Hansen T. Thuesen ACB, et al. Lancet Reg Health Eur. 2022 Nov 11;24:100529. doi: 10.1016/j.lanepe.2022.100529. eCollection 2023 Jan. Lancet Reg Health Eur. 2022. PMID: 36649380 Free PMC article. - An Analysis of Glucose Effectiveness in Subjects With or Without Type 2 Diabetes via Hierarchical Modeling.
Hu S, Lu Y, Tura A, Pacini G, D'Argenio DZ. Hu S, et al. Front Endocrinol (Lausanne). 2021 Mar 29;12:641713. doi: 10.3389/fendo.2021.641713. eCollection 2021. Front Endocrinol (Lausanne). 2021. PMID: 33854483 Free PMC article. - Impact of prolonged fasting on insulin secretion, insulin action, and hepatic versus whole body insulin secretion disposition indices in healthy young males.
Jørgensen SW, Hjort L, Gillberg L, Justesen L, Madsbad S, Brøns C, Vaag AA. Jørgensen SW, et al. Am J Physiol Endocrinol Metab. 2021 Feb 1;320(2):E281-E290. doi: 10.1152/ajpendo.00433.2020. Epub 2020 Dec 7. Am J Physiol Endocrinol Metab. 2021. PMID: 33284087 Free PMC article. Clinical Trial. - Oxidative Stress, Intrauterine Growth Restriction, and Developmental Programming of Type 2 Diabetes.
Rashid CS, Bansal A, Simmons RA. Rashid CS, et al. Physiology (Bethesda). 2018 Sep 1;33(5):348-359. doi: 10.1152/physiol.00023.2018. Physiology (Bethesda). 2018. PMID: 30109821 Free PMC article. Review. - Proteomics of Skeletal Muscle: Focus on Insulin Resistance and Exercise Biology.
Deshmukh AS. Deshmukh AS. Proteomes. 2016 Feb 4;4(1):6. doi: 10.3390/proteomes4010006. Proteomes. 2016. PMID: 28248217 Free PMC article.
References
- J Clin Endocrinol Metab. 1990 Dec;71(6):1508-18 - PubMed
- J Clin Endocrinol Metab. 1990 Dec;71(6):1544-51 - PubMed
- Lancet. 1992 Oct 17;340(8825):925-9 - PubMed
- Diabetes Care. 1992 Oct;15(10):1285-9 - PubMed
- Diabetes. 1992 Dec;41(12):1540-6 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous