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- November 20, 2008 |
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"Type 2 Diabetes and Cardiovascular Disease: The Neel Hypothesis Revisited"Prof. Peter J. Grant (biography)
English - 2006-05-07 - 50 minutes
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Summary :
In this presentation Prof. Grant talks about the Common Soil and Thrifty Genotype hypotheses and how they can be interpreted in light of new information that became available since their conception.
According to the Common Soil Hypothesis put forth by Stern in the 1980s, diabetes and cardiovascular disease are the same condition, underpinned by common genetic and environmental influences. There is some evidence to support this hypothesis, as well as a better understanding of the insulin resistance syndrome that has emerged in recent years.
In an early description of insulin resistance given by Reaven in 1988, obesity was not included as part of the syndrome, but it is now understood that adipocytes undergo changes under conditions of fat loading, causing pro-inflammatory responses; a pro-thrombotic effect due to impaired fibrinolysis; changes in regional blood flow due to expression of the renin angiotensin system; and metabolic changes related to adiponectin and leptin. Diabetes and cardiovascular disease are the same condition underpinned by an inflammatory atherothrombotic insulin resistance syndrome, concludes Prof. Grant.
According to the Thrifty Genotype Hypothesis put forward by Neel in the 1960s, insulin resistance has a survival advantage and is most likely to occur during periods of feast and famine. Prof. Grant further discusses how insulin resistance can be beneficial in the short term where it is cycled on a seasonal basis to keep the animal alive, and how abnormal cyclical responses in man underpin the cause of, and the link between diabetes and cardiovascular disease.
Copyright © 2006 E-MedHosting.com Inc.
Learning objectives :
After viewing this presentation the participant will be able to discuss:
- The primary function of inflammation and thrombosis;
- The physiological nature of the adipocyte response to fat loading;
- The inflammatory atherothrombotic insulin resistance syndrome underpinning diabetes and cardiovascular disease;
- The relationship of abnormal cyclical responses to diabetes and cardiovascular disease.
Bibliographic references :
Reaven, GM. Banting Lecture 1988. Role of Insulin Resistance in Human Disease Diabetes. 1988; 37(12): 1595-1607
Norhammar, A., Tenerz, A., Nilsson, G., Hamsten, A., Efendic, S., Ryden, L., Malmberg, K. Glucose Metabolism in Patients with Acute Myocardial Infarction and no Previous Diagnosis of Diabetes Mellitus: A Prospective Study The Lancet. June 2002; 359(9324): 2140-2144
Moreno, PR., Murcia, AM., Palacios, IF., Leon, MN., Bernardi, VH., Fuster, V., Fallon, JT. Coronary Composition and Macrophage Infiltration in Atherectomy Specimens From Patients With Diabetes Mellitus Circulation. 2000; 102: 2180
Vinik, AI., Erbas, T., Park, TS., Nolan, R., Pittenger, GL. Platelet Dysfunction in Type 2 Diabetes Diabetes Care. 2001; (24): 1476-1485
Freeman, MS., Mansfield, MW., Barrett, JH., Grant, PJ. Genetic Contribution to Circulating Levels of Hemostatic Factors in Healthy Families With Effects of Known Genetic Polymorphisms on Heritability Arteriosclerosis, Thrombosis, and Vascular Biology. 2002; 22: 506
Dunn, EJ., Ariens, RAS., Grant, PJ. The Influence of Type 2 Diabetes on Fibrin Structure and Function Diabetologia. 2005; 48(6): 1198-1206
Dunlap, JC. Molecular Bases for Circadian Clocks Cell. January 1999; 96(2): 271-290
Ando, H., Yanagihara, H., Hayashi, Y., Obi, Y., Tsuruoka, S., Takamura, T., Kaneko, S., Fujimura, A. Rhythmic Messenger Ribonucleic Acid Expression of Clock Genes and Adipocytokines in Mouse Visceral Adipose Tissue Endocrinology. 2005; 146(12): 5631-5636
Montagnani, M., Golovchenko, I., Kim, I., Koh, GY., Goalstone, ML., Mundhekar, AN., Johansen, M., Kucik, DF., Quon, MJ., Draznin, B. Inhibition of Phosphatidylinositol 3-Kinase Enhances Mitogenic Actions of Insulin in Endothelial Cells J. Biol. Chem. January 2002; 277(3): 1794-1799
Turek, FW., Joshu, C., Kohsaka, A., Lin, E., Ivanova, G., McDearmon, E., Laposky, A., Losee-Olson, S., Easton, A., Jensen, DR., Eckel, RH., Takahashi, JS., Bass, J. Obesity and Metabolic Syndrome in Circadian Clock Mutant Mice Science. May 2005; 308(5724): 1043-1045
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