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- March 10, 2010 |
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"Beta-cell Dysfunction in Pre-Diabetes"Dr. Christian Weyer (biography)
English - 2004-06-04 - 51 minutes
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Summary :
In this presentation Dr. Weyer presents data from cross-sectional, prospective and longitudinal studies showing the importance of beta-cell dysfunction in the pathogenesis of type 2 diabetes.
Different kinds of stimuli act on the pancreatic beta cells, which secrete insulin, pro-insulin, C-peptide and amylin, which is a gluco-regulatory hormone. The profile of amylin secretion by the beta-cell closely follows that of insulin secretion (1,2).
When comparing the early-phase glucose-stimulated insulin secretion between individuals, it is important to take into account the underlying insulin sensitivity. The disposition index is the product of acute insulin response to glucose (AIR) and insulin sensitivity (M). Mathematically speaking this product is a constant and the relationship between AIR and M is a hyperbolic one (3).
Cross-sectional studies demonstrate the impaired insulin secretion found in high risk groups (4, 5). Abnormalities in postprandial glucagon and GLP-1 responses are other hormonal abnormalities found in the pre-diabetic state (6).
Prospective studies have shown that low AIR and low M are independently predictive of progression from NGT to IGT and from IGT to type 2 diabetes mellitus (7). Also, fasting hyperinsulinemia predicts type 2 diabetes independently of low AIR and low M (8). Another prospective study found that high glucagon secretion and low insulin secretion predict glucose intolerance in postmenopausal women (9).
Longitudinal studies in the high risk Pima Indian group have provided information about the natural history of AIR and M in the pathogenesis of type 2 diabetes (10), and the effects of long-term weight loss on AIR and M in IGT subjects (11).
Dr. Weyer concludes his talk by presenting an interventional study in which bariatric surgery led to restoration of AIR in morbidly obese patients with IGT or type 2 diabetes (12).
Copyright © 2004 E-MedHosting.com Inc.
Learning objectives :
After viewing this presentation the partcipant will be able to discuss:
- Differences in acute insulin response to glucose (AIR) and insulin sensitivity (M) between groups at high risk for type 2 diabetes
- Other hormonal abnormalities found in the pre-diabetic state
- The value of low AIR, low M and fasting hyperinsulinemia in predicting the risk of type 2 diabetes
Bibliographic references :
1. Weyer C, Maggs DG, Young AA, Kolterman OG.Amylin replacement with pramlintide as an adjunct to insulin therapy in type 1 and type 2 diabetes mellitus: a physiological approach toward improved metabolic control.
Curr Pharm Des. 2001 Sep;7(14):1353-73.
2. Negar G. Knowles, MA, Melinda A. Landchild, MA, Wilfred Y. Fujimoto, MD and Steven E. Kahn, MB, CHB.Insulin and Amylin Release Are Both Diminished in First-Degree Relatives of Subjects With Type 2 Diabetes Diabetes Care.2002;25:292-297.
3. Pratley RE, Weyer C.The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus.Diabetologia. 2001 Aug;44(8):929-45.
4. Weyer, Christian MD; Pratley, Richard E. MD; Tataranni, P. Antonio MD.Role of insulin resistance and insulin secretory dysfunction in the pathogenesis of type 2 diabetes mellitus: lessons from cross-sectional, prospective, and longitudinal studies in Pima Indians.Current Opinion in Endocrinology & Diabetes. 9(2):130-138, April 2002.
5. Kahn SE.The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes.
Diabetologia. 2003 Jan;46(1):3-19.
6. Mai-Britt Toft-Nielsen, Mette B. Damholt, Sten Madsbad, Linda M. Hilsted, Thomas E. Hughes, Birgitte K. Michelsen and Jens J. Holst.Determinants of the Impaired Secretion of Glucagon-Like Peptide-1 in Type 2 Diabetic Patients JCEM.2001;Vol. 86, No. 8 3717-3723.
7. Christian Weyer, MD, P. Antonio Tataranni, MD, Clifton Bogardus, MD and Richard E. Pratley, MD.Insulin Resistance and Insulin Secretory Dysfunction Are Independent Predictors of Worsening of Glucose Tolerance During Each Stage of Type 2 Diabetes Development Diabetes Care 24:89-94, 2001.
8. C Weyer, RL Hanson, PA Tataranni, C Bogardus and RE Pratley.A high fasting plasma insulin concentration predicts type 2 diabetes independent of insulin resistance: evidence for a pathogenic role of relative hyperinsulinemiaDiabetes.2000; Vol 49, Issue 12 2094-2101.
9. Larsson H, Ahren B.Glucose intolerance is predicted by low insulin secretion and high glucagon secretion: outcome of a prospective study in postmenopausal Caucasian women.Diabetologia. 2000 Feb;43(2):194-202.
10. Christian Weyer, Clifton Bogardus, David M. Mott and Richard E. Pratley.The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus J Clin Invest, September 1999, Volume 104, Number 6, 787-794.
11. Weyer C, Hanson K, Bogardus C, Pratley RE.Long-term changes in insulin action and insulin secretion associated with gain, loss, regain and maintenance of body weight.Diabetologia. 2000 Jan;43(1):36-46.
12. Eftihia V. Polyzogopoulou, Fotios Kalfarentzos, Apostolos G. Vagenakis, and Theodore K. Alexandrides. Restoration of Euglycemia and Normal Acute Insulin Response to Glucose in Obese Subjects With Type 2 Diabetes Following Bariatric Surgery Diabetes 52:1098-1103, 2003.
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