DR.

SIDRA SADIQ

INSULIN RESISTANCE
Insulin:

 Polypeptide anabolic hormone

 51 amino acids in two chains A And B joined
by disulfide bridges.(molecular mass 5808)
 Langerhans:clusters of cells(beta cells)
 Normal blood insulin level:2-25µIU/ml
 (12-150pmol/L)
 Measured by immunoassay/isotope dilution
mass spectrometry.
continued

 Pre pro insulin normally not detected as

rapidly converted into pro insulin.
 Pro insulin is the major storage form(low
biological activity)
 Pro insulin undergoes proteolytic cleavage in
Golgi apparatus to insulin and C peptide.
Insulin resistance definition:

 The condition in which normal amounts of

insulin are inadequate to produce a normal
insulin response from fat, muscle & liver cells
OR
 The decrease biological response to normal
concentrations of circulating insulin.
Etiology of IR:

 Genetic factors
 Medications: steroid ,glucosamine
 obesity
 Metabolic syndrome
 Pregnancy
 Infection
 Severe stress/illness
Measurement of insulin resistance:

 Hyperinsulinemic euglycemic clamp

 Insulin tolerance test
 Homeostatic model assessment of insulin
resistance(HOMA -IR)
 Quantitative insulin sensitivity check index
(QUICKI)
Hyperinsulinemic euglycemic clamp:

 Quantifying insulin secretion and resistance

 High insulin infusion rate:80 mU/m2 body
surface area
 Variable infusion rate of dextrose to keep
blood glucose levels in the range of 90-100
mg/dl
 A higher glucose infusion rate (GIR) indicates
better insulin sensitivity
Insulin tolerance test:

 First method developed to measure in vivo

insulin sensitivity
 Gold standard for assessing integrity of
hypothalamic pituitary adrenal axis.
 Clinically use before surgery to assess peak
adrenal capacity
Homeostatic model assessment of
insulin resistance(HOMA IR):
 Fasting plasma glucose & fasting plasma
insulin concentrations are used to estimate IR
 Used to assess hepatic insulin sensitivity
 A lower score indicates better insulin
sensitivity
 fasting Plasma glucose(mg/dl)/18 x serum
insulin( nmol/L )/22.5
 Normal sensitivity=2.24
Quantitative insulin sensitivity check
index(QUICKI)
 Derived using the inverse of the sum of
logarithms of fasting insulin and fasting
glucose
 1/log fasting insulin (µU/mL) + log fasting
glucose(mg/dl)
 advantage: can be obtained from a fasting
blood sample.
HIGH RISK POPULATION:
 Overweight (BMI-25)
 waist -35 inches( women) or with a waist -40 inches(men)
 Latino, African American, Native American or Asian
American
 Family history with type 2 diabetes, hypertension or
arteriosclerosis
 gestational diabetes
 Hypertension (>130/85mmHg)
 High blood TG (>150mg/dl or 1.70mmol/L)
 Low HDL-C (<50mg/dl or 1.30mmol/L)
 Fasting plasma glucose (>110 mg/dl or 6.1mmol/L)
Some medical conditions associated
with IR:
 Metabolic syndrome
 Abnormally sedentary lifestyle(aging & obesity)
 Type 2 diabetes
 Fatty liver
 Arteriosclerosis
 Skin lesions or skin tags:achanthosis nigricans
 Reproductive abnormalities in women (PCOS)
 Hyperandrogens
 Growth abnormalities
The insulin resistance syndrome:

Clinical manifestations:
 Central obesity
 Acanthosis nigricans
 Glucose intolerance
 Hypertension
 Atherosclerosis
 Polycystic syndrome
 Biochemical abnormalities:
 Glucose intolerance:
 Insulin resistance
 Hyperinsulinemia
 dyslipidemia:
 High TG ,Low HDL-C
 Small, dense LDL
 Vascular abnormalities
 Abnormal thrombolysis
 Endothelial & smooth muscle cell
dysfunction
 Metabolic syndrome (syndrome x)
 Central obesity
 Hypertension
 Dyslipidemia
 Insulin resistance
Treatment of IR:

 Weight reduction
 Exercise &
 Dietary modifications
IR & OBESITY:

 Weight loss:
 Reduces insulin levels
 Improves status-clinical
 -metabolic
 -endocrinal
 Androgen level falls by 44%
 Weight loss is the first therapeutic option
Dietary components which may affect
insulin resistance:
 Low IR:
 Whole grains
 Fruits & vegetables
 Low fat dairy products
 Magnesium
 Calcium
 Dietary fiber
 Omega-3 fatty acids
 High IR:
 Saturated fat
 Salt (deficiency or excess)
 Alcohol(30g/day)
IR COUNSELLING:

 Increased intake of fruits, vegetables & low

fat dairy products is associated with
 Increased insulin sensitivity
 decreased risk of metabolic syndrome
 decreased risk of type 2 diabetes
 decreased risk of hypertension
Insulin resistance at a glance:

 A condition in which the cells of the body

become resistant to the hormone ,insulin.
 may be part of the metabolic syndrome &
associated with development of heart
disease.
 precedes the development of type 2 diabetes
 Medical conditions associated with IR:
fattyliver,arteriosclerosis,acanthosis
nigricans, skin tags & reproductive
abnormalities in women
 While there is a genetic component insulin
resistance can be managed with diet,
exercise & medications.