1. Conditions associated with insulin resistance
Atherosclerosis
Central obesity
PCOS
Hypertension
Type 2
diabetes
Hypercoagulation/
impaired fibrinolysis
Hyperinsulinaemia
Microalbuminuria
Endothelial dysfunction
Low grade chronic
systemic inflammation
PCOS - Polycystic Ovarian Syndrome
Dyslipidaemia
INSULIN
RESISTANCE
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Insulin resistance is associated with the development of a clustering of metabolic disorders, including type 2 diabetes, obesity, hypertension, dyslipidaemia, and atherosclerosis, known as the insulin resistance syndrome (also known as the metabolic syndrome or syndrome X).
Adapted from DeFronzo. Diabetes Care 1991; 14:

2. Progressive decline of HOMA beta-cell function over time
100
Start of treatment 80 60
HOMA beta-cell function (%)
p<0.0001 40 20
The United Kingdom Prospective Diabetes Study (UKPDS) compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment with diet on the risk of microvascular or macrovascular complications in patients with type 2 diabetes in a randomised controlled trial.
The study showed that beta-cell function deteriorated over six years in the 37% of subjects allocated to and remaining on diet therapy at six years (n=376).
There was a significant decrease in beta-cell function from 1 to 6 years (p<0.0001). From these data, it can be seen that the decline of beta-cell function occurs many years before the diagnosis of diabetes. Beta cell function is thought to decline by 1% per year during normal ageing.
Reference
United Kingdom Prospective Diabetes Study Group (UKPDS 16). Diabetes. 1995;
44:
Diet-treated, n=376
Time from diagnosis (years)
Adapted from UKPDS 16. Diabetes. 1995; 44:

3. Beta-cell dysfunction in diabetes
Insulin secretion in lean mouse
Insulin secretion in diabetic mouse
Lister CA et al. Diabetologia 1998; 41 (Suppl 1): A169. Abstract 660

4. Homeostasis Model Assessment (HOMA)
Clamp technique measures under hyperinsulinaemic conditions1 – considered the ‘gold standard’
HOMA estimates insulin sensitivity and beta-cell function using fasting insulin and glucose2 from a single sample and correlates well with other insulin sensitivity tests
Well correlated with other insulin sensitivity tests (eg intravenous glucose tolerance test) and beta-cell function tests (eg hyperglycaemic clamp)
There is a feeling that the imprecision of the homeostasis model assessment (HOMA) limits its clinical application; however, the significant correlations of the HOMA estimates with independent measurements of insulin resistance support the theoretical background of the analysis.1
Interestingly, a small study (n=63) by Lansang MC et al compared the euglycaemic clamp and the HOMA in patients with and without hypertension. It was concluded that the HOMA can be used reliably for measuring insulin resistance in hypertension.2
References
1. Matthews DR. Diabetologia 1985; 28:
2. Lansang MC et al. Am J Hypertens 2001; 14:
1. DeFronzo RA et al. Am J Physiol 1979; 237: E214-E Matthews DR et al. Diabetologia 1985; 28:

5. Homeostasis Model Assessment (HOMA)
Normal: % beta-cell function:
insulin resistance (R) = 1
20  insulin* (mU/ml)
glucose* (mmol/l) - 3.5
Beta-cell function (%) =
insulin* (mU/ml)  glucose* (mmol/l)
22.5
Insulin resistance =
The model computes values from fasting insulin and glucose measurements.
In homeostasis, with 100% beta-cell function, normal insulin resistance is assigned a value of 1.
The percentage of beta-cell function is determined by the following equation:
20  fasting insulin level [µU/ml]  FPG level [mmol/l] - 3.5
The degree of insulin resistance is calculated by multiplying fasting insulin (µU/ml) by FPG (mmol/l) and dividing by 22.5.
*fasting levels
Haffner S. Diabetes Care 1996; 19: 1139

6. Homeostasis Model Assessment (HOMA)50 40 30 20 10
b=200%
Decreasing b-cell
function (b)
b=100%
Increasing
insulin
resistance (R)
R=16
Basal plasma insulin
(mU/ml)
b=50%
R=8
b=25%
This graphic representation of HOMA shows the model prediction of steady-state plasma glucose and insulin concentrations for a series of different beta-cell functions (red) and insulin resistance values (yellow).
For any individual, FPG and fasting insulin may be entered on the grid, and the estimated beta-cell function and insulin resistance may be obtained.
R=2
R=4
R=1
R=2
R=½ 2 4 6 8 10 12 14
Basal plasma glucose (mmol/l)
Matthews et al. Diabetologia 1985; 28: 412