diabetes and insulin resistance kari kohrs rd ldn cde uicmc nutrition & wellness center
TRANSCRIPT
DIABETES AND INSULIN RESISTANCE
KARI KOHRS
RD LDN CDE UICMC NUTRITION &
WELLNESS CENTER
DIABETES PREVALANCE
Third leading cause of death-- United States
18 million diagnosedGrowing at the rate of
3 new cases q 2 mins Alarming incidence of
type 2 DM18 yr old and younger
type 2 DM skyrocking
THE OBESITY PROBLEM 80% of Type 2 DM are overweight Particular forms of obesity--
• Abdominal• Truncal• Visceral• Subcutaneous
Central body obesity and insulin resistance are related--releases more FFA
Insulin resistance has 2 causes-high levels of circulating fat and inheritance
Causes & Aggravating Factors of Insulin Resistance
Combination of genetic and lifestyle factors Heredity--close relatives with Type 2 risk Ethnic group--Native Americans, AA, Hispanics Abdominal obesity interferes w/ insulin action Lack of exercise and high caloric diet Stressful lifestyle—stress hormones released Pregnancy-increase in weight and production
of placental hormones that blood glucose levels
INSULIN RESISTANCE DEFINED The body RESISTS taking
sugar into the cellsInsulin can’t link with
the receptors on the surfaces of cells because there aren’t enough receptors
Something goes wrong in the chemical reaction at the time of linking
The body can’t use the sugar in the blood & hi BG develops bringing on DM symptoms
Certain proteins and/or enzymes released by stored fat act on muscle and liver cells to impair the way they “read” insulin signals to process glucose
Visceral abdominal fat sheds more free fatty acids; elevated TG levels increases insulin production promoting further fat storage
Other notes…..
Up to 92% of people with Type 2 diabetes demonstrate insulin resistance
Insulin resistance and beta-cell dysfunction can precede diagnosis of Type 2 diabetes by up to 12 years
Insulin resistance can be identified by these markers: 1) Hyperglycemia 2) Dyslipidemia-
high triglyceride, low HDL
3) Central obesity 4) Hypertension-
greater than 130/80
FAT, TRIGLYCERIDES, AND INSULIN
Abdominal fat continually releases triglycerides into the branch of the bloodstream that feeds the liver
This increases the body’s need for insulin release
Demand for more insulin causes the pancreas to work harder to produce elevated insulin levels
High levels of insulin in blood down-regulate the affinity for insulin that insulin receptors all over the body have naturally-”tolerance” causes > IR
INSULIN RESISTANCE The vicious cycle of insulin resistance
Insulin Resistance
Overeating
Truncal obesity
High blood sugar
HungerCraving carbohydrates
Excessiveinsulin productionby reduced number of beta cells
Beta cell burnout
The Culprit? FAT?
And we aren’t talking about dietary fat Triglycerides are in circulation at some
level in the bloodstream at all times High triglyceride levels are not so much
the result of intake of dietary fat as they are of excessive carbohydrate consumption and existing body fat
Visceral fat-concentrated around middle of the body, surrounding the intestine
Or is the Culprit…?Mutations & genetic error?
The importance of PPARy--Peroxisome Proliferator Activated Receptors are found in or on cells in muscle, fat, and liver tissue and are involved in energy metabolism
PPARs regulate the action of insulin
Activation of PPARy results in decreased insulin resistance which in turn helps glucose enter the cells
or……..PC-1…...
PC-what?
Researchers have identified a protein called PC-1 that shuts down the insulin receptor, which creates insulin resistance
This protein is prevalent in most people with Type 2 diabetes compared to people without diabetes. Too much of the inhibitor protein is made in some people and the insulin receptor cannot do its job
How does it affect the chain? PC-1 “desensitizes” insulin
receptors. The overproduction of PC-1 is a genetically determined trait
The high levels of PC-1 protein lead to insulin resistance
A series of defects limiting function exist
FYI-Researchers are also now looking for an obesity gene
TREATMENT?--LOSE fat or ADD medicine or both
Weight reduction can reduce insulin resistance, and reduce the need for medication. Eat less!
Hypocaloric diet Exercise Biguanide---Metformin Thiazolidinediones---
Pioglitazone/Rosiglitazone
Biguanides vs TZD’s Biguanides--Glucophage
or Glucophage XR Most widely prescribed Don’t cause
hypoglycemia Does not promote
weight gain Positive effect on blood
lipid levels which can reduce insulin resistance
Suppress liver glucose Enhances sensitivity of
peripheral and hepatic tissues to insulin
Thiazolidinediones--Actos (pioglitazone) or Avandia (rosiglitazone)
Insulin sensitizers target insulin receptors in muscle and fat cells to increase insulin sensitivity in the body
Lowers glucose-reduce hyperinsulinemia
Can be effective in lowering TG levels & raising HDL’s
Activates PPAR receptors to control glucose transport
In Conclusion…..IR Upper body subcutaneous fat-obesity Genetics-inheritance gene mutation PPAR Protein PC-1 insulin receptor inhibitor Combination of? Prevention? What can an individual at risk
do? Decrease upper body obesity or introduce a form of therapy than can correct the abnormal adipose tissue FFA release that may improve the metabolic abnormalities seen in upper body obesity even if weight loss is not successful
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3) UK Prospective Diabetes Study 16: overview of 6 years therapy of type 2 diabetes: a progressive disease. Diabetes. 1995; 44:1249-1258.
4) Marx N, Bourcier T, Sukhova GK, Libby P, Plutzky J. PPARy activation in human endothelial cells increases plasminogen activator inhibitor Type 1 expression: PPARy as a potential mediator in vascular disease. Arterioscler Thromb Vasc Biol. 1999; 19:546-551
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