DIABETES AND INSULIN RESISTANCE KARI KOHRS RD LDN CDE

DIABETES AND
INSULIN RESISTANCE
KARI KOHRS
RD LDN CDE
UICMC NUTRITION &
WELLNESS CENTER
DIABETES PREVALANCE
Third leading cause of
death-- United States
 18 million diagnosed
Growing at the rate of
3 new cases q 2 mins
 Alarming incidence of
type 2 DM
18 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
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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 cells
Insulin 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  Insulin resistance
with Type 2 diabetes
can be identified by
demonstrate insulin
these markers:
resistance
1) Hyperglycemia
 Insulin resistance
2) Dyslipidemia- high
triglyceride, low HDL
and beta-cell
3) Central obesity
dysfunction can
4) Hypertensionprecede diagnosis of
greater than 130/80
Type 2 diabetes by up
to 12 years
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
Overeating
Beta cell
burnout
Excessive
insulin production
by reduced number
of beta cells
Truncal obesity
Insulin Resistance
Craving carbohydrates
High blood sugar
Hunger
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
 Thiazolidinediones--Actos
(pioglitazone) or Avandia
 Most widely prescribed
(rosiglitazone)
 Biguanides--Glucophage
or Glucophage XR
 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
 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
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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
Resources
 1) Haffner SM, D’Agostino R Jr, Mykkaren L,et al. Insulin sensitivity in subjects with
Type 2 diabetes: relationship to cardiovascular risk factors: the Insulin Resistance
Atherosclerosis Study. Diabetes Care. 1999; 22:562-568
 2) Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs at least 4-7
years before clinical diagnosis. Diabetes Care. 1992;15:815-819
 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
 5) Lovisach M, Rehman N, Carter L, et al. Distribution of peroxisome proliferatoractivated receptors (PPARs) in human skeletal muscle and adipose tissue: relation to
insulin action. Diabetologia. 2000; 43:304-311
 6) Touchette P, Sherrye L, American Diabetes Association Complete Guide to
Diabetes. 1999: 1:25
 7) Bernstein R.K., Dr. Bernstein’s Diabetes Solution. 2000
 8) Beaser R.S., Joan V.C. Hill J.V.C, The Joslin Guide to Diabetes. 2004
 9) Saudek C.D., Rubin R.R., The Johns Hopkins Guide to Diabetes. 2001
 10) Ford-Martin P., Ian Blumer. The Everything Diabetes Book. 2004;3:22,166-168