UniS
MSc in Diabetes
A population approach
Impaired glucose tolerance
and undiagnosed diabetes
Ross Lawrenson
Postgraduate Medical School
University of Surrey
Metabolic syndrome
• Impaired glucose tolerance
• Undiagnosed Type 2 diabetes
Theories on the aetiology of
Type 2 diabetes
• Barker hypothesis
• Reaven Syndrome
• Thrifty genotype
Barker hypothesis
• The thrifty phenotype
Odds ratio of NIDDM and IGT
related to birth weight
Odds Ratio
8
7
6
5
4
3
2
1
0
<=5.5
5.5-6.4
6.5-7.4
7.5-8.4
8.5-9.4
Birth Weight in pounds
>9.5
Barker hypothesis
• Malnutrition in the prenatal and early
infant years. (Hales and Barker)
• Beta cells increase of 130 times between
12 th intra-uterine week and 5 th post
natal month.
• Malnutrition.
• Obesity in later life.
Reaven syndrome
• First described by Himsworth in 1936
• Described in New Zealand by Ian Prior
in 1966 in Maori (obesity, hypertension
diabetes and gout)
• Syndrome X sometimes called Reaven
syndrome after Gerry Reaven
Relationship between glucose uptake
and fasting plasma glucose
700
600
500
Normal
IGT
NIDDM
400
300
200
100
0
0
50
100
150
Reaven G. Diabetes 1988
200
250
300
Reaven syndrome
• Reaven syndrome or Syndrome X
– Resistance to insulin-stimulated glucose
uptake
– Hyperinsulinaemia or glucose intolerance
– Hypertension
– Decreased HDL
– Increased VLDL
– Central obesity
Thrifty genotype
• Thrifty genotype
– Ability to lay down fat
– Survive times of hardship
– Alternative metabolic pathway in high
protein diet
Age adjusted prevalence of NIDDM and
IGT in adults aged over 20 years
NIDDM
known
NIDDM
new
IGT
Total
Male
european
1.4%
Male
Asian
7.2%
Female
European
1.5%
Female
Asian
6.8%
1.8%
5.2%
3.1%
4.3%
5.7%
9.8%
6.8%
11.2%
8.9%
20.2%
11.4%
22.3%
Simmons D. The Coventry Diabetes Study. Quarterly Journal of Medicine.
1991; 81: 1021-1030
Prevalence of undiagnosed NIDDM with age in New
Zealand adults aged over 20 years. The overall crude
rate was 56/3896 (1.4%).
Percent with undiagnosed NIDDM
6
5
4
3
2
1
0
20-24
30-34
25-29
40-44
35-39
50-54
45-49
60-64
55-59
Age
70-74
65-69
80-84
75-79
90+
85-89
Prevalence of undiagnosed NIDDM per
1000 people screened by BMI.
Prevalence per 1000
50
40
30
20
10
0
0-24
25-29
30-34
BM I
35-39
40+
Mean BMI of men and women by
ethnic origin.
Mean BMI
95% CI
% with BMI >=30
Maori male
30.7
30.1 - 31.3
55%
Maori ethnic origin male
29.3
27.7 - 30.9
46%
European male
27.1
26.8 - 27.3
23%
Maori female
30.6
30.0 - 31.2
47%
Maori ethnic origin female
28.0
26.6 - 29.4
32%
European female
26.4
26.2 - 26.7
23%
Variables associated with the presence of
undiagnosed diabetes in people 40 years.
Adjusted Odds Ratio
95% Confidence interval
Age
1.05
1.02 -1.07
BMI
1.09
1.03 - 1.15
Thirst
2.28
1.11 - 4.68
Ethnicity
2.26
1.08 - 4.72
Diastolic blood pressure
1.02
1.00 - 1.05
Gender
1.49
0.85 - 2.62 ns
Smoking
.88
0.41 - 1.89 ns
Urinary frequency
1.04
0.57 - 1.89 ns
Significant factors associated with undiagnosed
diabetes in Europeans over the age of 40 years.
Variable
Adjusted OR
95% Confidence
interval
Age
1.07
1.04 - 1.10
BMI
1.13
1.06 - 1.21
Family history
2.34
1.16 - 4.71
Study using the General Practice Research
Database - characteristics of subjects
Type 1
Type 2
Mean age in 1992
33.4
63.6
Mean age at diagnosis (yrs)
18.0
56.7
Mean duration to 1992 (yrs)
16.2
7.1
5.3
5.1
Mean period of follow-up (yrs)
Total of 5528 type 1 and 25707 type 2 patients
Impaired glucose tolerance
• This group are asymptomatic and do not
have diabetes
• Do not suffer the microvascular
complications
• The diagnosis is important because:
– High rate of macrovascular disease
– A number will eventually become diabetic
– Secondary prevention in this group may reduce
morbidity and mortality
Prevalence
C
o
u
n
t
r
y
/
R
a
c
e M
a
l
e F
e
m
a
l
e
N
a
u
r
u
1
8
.
4
1
8
.
3
P
a
p
u
a
N
e
w
G
u
i
n
e
a3
.
5
1
.
2
I
t
a
l
y
4
.
9
7
.
7
A
u
s
t
r
a
l
i
a
4
.
3
3
.
3
U
S
A
1
0
.
2
1
1
.
1
C
o
v
e
n
t
r
y
E
u
r
o
C
o
v
e
n
t
r
y
A
s
i
a
n
5
.
7
9
.
8
6
.
8
1
1
.
2
Progression to diabetes
S
u
b
j
e
c
t
s
s
t
u
d
i
e
d
R
a
t
e
p
e
r
y
e
a
r
B
i
r
m
i
n
g
h
a
m
S
w
e
d
e
n
m
e
n
4
.
5
1
.
7
B
e
d
f
o
r
d
J
a
p
a
n
L
o
n
d
o
n
m
e
n
1
.
5
2
.
0
2
.
9
Impaired glucose tolerance
• After 10 years between 15 and 45% will have diabetes
• After 10 years about 1/3 will be normal
• If OGTT is repeated within 3 months approximately 50%
will have a normal GTT
• Tukitonga showed that those with IGT in Niue who
progressed to diabetes were more likely to be sedentary
whilst those who were active were more likely to return to
normal
• Tuomilheto J, Lindstrom J, Eriksson JG, Valle TT,
Hamalainen H, Ilanne-Parikka P et al. Prevention of Type 2
diabetes mellitus by changes in lifestyle among subjects
with impaired glucose tolerance. New England Journal of
Medicine 2001; 344(18) 1343-9
Summary
• Type 2 diabetes is increasing
• Intervention strategies are needed to
reduce incidence
• Identifying undiagnosed patients with
type 2 diabetes may reduce onset of
complications
• Identifying and treating IGT has
proved worthwhile