ir and hyperinsulinemia insulin resistance: a survival mechanism, gone awry stan schwartz md,facp...
TRANSCRIPT
![Page 1: IR and Hyperinsulinemia Insulin Resistance: A Survival Mechanism, Gone Awry Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical](https://reader035.vdocuments.us/reader035/viewer/2022072006/56649f575503460f94c7b49c/html5/thumbnails/1.jpg)
IR and Hyperinsulinemia
Insulin Resistance: Insulin Resistance:
A Survival Mechanism, Gone AwryA Survival Mechanism, Gone Awry
Stan Schwartz MD,FACPAffiliate, Main Line Health System
Emeritus, Clinical Associate Professor of Medicine, U of Pa.
Part 3
![Page 2: IR and Hyperinsulinemia Insulin Resistance: A Survival Mechanism, Gone Awry Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical](https://reader035.vdocuments.us/reader035/viewer/2022072006/56649f575503460f94c7b49c/html5/thumbnails/2.jpg)
Peripheral Insulin Resistance- Induced Hyperinsulinemia
has Adverse Downstream Effects
Insulin
Met
abol
ic p
athw
ay
(PI3
K)M
itogenic pathway
(MAPK)
Proliferation, ENDOTHELIAL DYSFUCTION, INFLAMMATION
Glucose transportGlykogen syntheseHyperglycemia
Hyperinsulinemia
Insulin-Resistance
![Page 3: IR and Hyperinsulinemia Insulin Resistance: A Survival Mechanism, Gone Awry Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical](https://reader035.vdocuments.us/reader035/viewer/2022072006/56649f575503460f94c7b49c/html5/thumbnails/3.jpg)
INACTIVITY,DIET
INFLAMMATION, OXIDATIVE STRESS
INCREASED PAI-1,NFKB,MMPS,ROS,AP-1,Egr-1
FFAs
![Page 4: IR and Hyperinsulinemia Insulin Resistance: A Survival Mechanism, Gone Awry Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical](https://reader035.vdocuments.us/reader035/viewer/2022072006/56649f575503460f94c7b49c/html5/thumbnails/4.jpg)
Abnormalities seen with IR/ Compensatory Hyperinsulinemia:
Risk Factors for ASVD
![Page 5: IR and Hyperinsulinemia Insulin Resistance: A Survival Mechanism, Gone Awry Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical](https://reader035.vdocuments.us/reader035/viewer/2022072006/56649f575503460f94c7b49c/html5/thumbnails/5.jpg)
![Page 6: IR and Hyperinsulinemia Insulin Resistance: A Survival Mechanism, Gone Awry Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical](https://reader035.vdocuments.us/reader035/viewer/2022072006/56649f575503460f94c7b49c/html5/thumbnails/6.jpg)
Insulin Resistancea.Increased liver production sugarb.Decreased peripheral Glucose Uptakec.Increased production FFA from Adipose tissue (alternate fuel source)
1. But potential for Maladaptive Effects of IR on Body ifA. Biologic Clock DysfunctionB Peripheral IR causes HYPERINSULINEMIA-
increases MAP-kinase pathway- cytokines , etc inc ASCVD risk factors
C. Visceral Adipose tissue-1. excessive FFA release, decrease b-cell function= lipotoxicityin genetically susceptible perrson, inc. risk/severity DM2. adipocytokines increase inflammation, endothelial dysfunction
![Page 7: IR and Hyperinsulinemia Insulin Resistance: A Survival Mechanism, Gone Awry Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical](https://reader035.vdocuments.us/reader035/viewer/2022072006/56649f575503460f94c7b49c/html5/thumbnails/7.jpg)
Insulin Resistance Related to Visceral Fat:Normal vs. Type 2 Diabetes
Normal Type 2 Diabetes
Fujimoto, et al. Obes Res. 1994;2:364-371.
![Page 8: IR and Hyperinsulinemia Insulin Resistance: A Survival Mechanism, Gone Awry Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical](https://reader035.vdocuments.us/reader035/viewer/2022072006/56649f575503460f94c7b49c/html5/thumbnails/8.jpg)
The Adipocytokine Syndrome: A New Model for Insulin Resistance and ß-
Cell Dysfunction
Pancreas
FFA, TNF Leptin
![Page 9: IR and Hyperinsulinemia Insulin Resistance: A Survival Mechanism, Gone Awry Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical](https://reader035.vdocuments.us/reader035/viewer/2022072006/56649f575503460f94c7b49c/html5/thumbnails/9.jpg)
![Page 10: IR and Hyperinsulinemia Insulin Resistance: A Survival Mechanism, Gone Awry Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical](https://reader035.vdocuments.us/reader035/viewer/2022072006/56649f575503460f94c7b49c/html5/thumbnails/10.jpg)
Flatbush diabetes
![Page 11: IR and Hyperinsulinemia Insulin Resistance: A Survival Mechanism, Gone Awry Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical](https://reader035.vdocuments.us/reader035/viewer/2022072006/56649f575503460f94c7b49c/html5/thumbnails/11.jpg)
Insulin Resistancea.Increased liver production sugarb.Decreased peripheral Glucose Uptakec.Increased production FFA from Adipose tissue (alternate fuel source)
1. But potential for Maladaptive Effects of IR on Body ifA. Biologic Clock DysfunctionB Peripheral IR causes HYPERINSULINEMIA-
increases MAP-kinase pathway- cytokines , etc inc ASCVD risk factors
C. Visceral Adipose tissue-1. excessive FFA release, decrease b-cell function= lipotoxicityin genetically susceptible perrson, inc. risk/severity DM2. adipocytokines increase inflammation, endothelial dysfunction