1 / 12

IR and Hyperinsulinemia

Delve into the mechanisms and implications of hyperinsulinemia and insulin resistance on diabetes risk and complications, exploring genetic, environmental, and lifestyle factors. Learn about central vs. peripheral insulin resistance, pathogenic constructs, and potential therapeutic implications.

davidhunt
Download Presentation

IR and Hyperinsulinemia

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. IR and Hyperinsulinemia Insulin Resistance: A Survival Mechanism, Gone Awry Part 1 Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical Associate Professor of Medicine, U of Pa. stschwar@gmail.com

  2. Traditional View:Natural History of Type 2 Diabetes Age 0-15 15-40+ 15-50+ 25-70+ Envir.+ Other Disease Genes Macrovascular Complications Obesity (visceral) Poor Diet Inactivity IR phenotypeAtherosclerosisobesityhypertensionHDL,TG, HYPERINSULINEMIA Endothelial dysfunctionPCO,ED Disability Insulin Resistance MICVAAmp pp>7.8 DEATH IGT Type II DM  Beta Cell Secretion BlindnessAmputationCRF EyeNerveKidney Risk of Dev. Complications ETOHBPSmoking Disability Microvascular Complications

  3. Pathogenic, β-Cell-Centric Construct for All Diabetes Implications for Classification, Diagnosis, Prevention, Therapy, Research EPIGENITICS EPIGENITICS Environmental Inflam. Triggers eg: viral,endocrine disruptors, food AGE’s, biome Inflammatory; Abnormal Immune Modulation Resistance (obesity) inflammatory adipokines Polygenic- other Monogenic (HLA) PHENOTYPE Gene β-Cell secretion/mass Polygenic Monogenic - MODY − Mitochondrial Resistance-(obesity)-FFA Poor diet, inactivity Non Inflammatory endocrine disruptors, food AGE’s ,biome Environmental Triggers

  4. Implications for Therapy • Treat Central Mechanisms IR • Treat Peripheral IR- fat, liver, muscle • Treat Inflammation • Treat Biome

  5. Insulin Resistance- Provide Substrate for the Brain • Increased liver production sugar • Decreased peripheral Glucose Uptake • Increased production FFA from Adipose tissue (alternate fuel source) • But potential for Maladaptive Effects of IR on Body if • A. Biologic Clock Dysfunction • B Peripheral IR causes HYPERINSULINEMIA- • increases MAP-kinase pathway- cytokines , • etcinc ASCVD risk factors • C. Visceral Adipose tissue- • 1.excessive FFA release, decrease b-cell function= lipotoxicity • in genetically susceptible perrson, inc. risk/severity DM • 2. D. adipocytokines increase inflammation, endothelial dysfunction

  6. Insulin Resistance • Increased liver production sugar • Decreased peripheral Glucose Uptake • Increased production FFA from Adipose tissue (alternate fuel source) • But potential for Maladaptive Effects of IR on Body if • A. Biologic Clock Dysfunction • B Peripheral IR causes HYPERINSULINEMIA- • increases MAP-kinase pathway- cytokines , • etcinc ASCVD risk factors • C. Visceral Adipose tissue- • 1.excessive FFA release, decrease b-cell function= lipotoxicity • in genetically susceptible perrson, inc. risk/severity DM • 2. D. adipocytokines increase inflammation, endothelial dysfunction

  7. Central Insulin Resistance (IR) • Increased liver production sugar • Decreased peripheral Glucose Uptake • Increased production FFA from Liver and Adipose tissue (alternate fuel source) • Normal Response to Hibernation, Migration, Periods of Food lack!! • BUT ALSO, Normal DIURNAL VARIATION IN INSULIN SENSITIVITY • 2. Centrally Induced IR Exacerbated by: • obesity, high fat diets, high CHO diets, abnormal sleep cycle, decreased • exercise: translates to IR all day long

  8. Day Night

More Related