Prospective study of risk factors for development of NIDDM in middle aged British men

Article (PDF Available)inBMJ Clinical Research 310(6979):560-4 · April 1995with59 Reads
DOI: 10.1136/bmj.310.6979.560 · Source: PubMed
Abstract
To determine the risk factors for noninsulin dependent diabetes in a cohort representative of middle aged British men. Prospective study. 7735 men aged 40-59, drawn from one group practice in each of 24 towns in Britain. Known and probable cases of diabetes at screening (n = 158) were excluded. Non-insulin dependent diabetes (doctor diagnosed) over a mean follow up period of 12.8 years. There were 194 new cases of non-insulin dependent diabetes. Body mass index was the dominant risk factor for diabetes, with an age adjusted relative risk (upper fifth to lower fifth) of 11.6; 95% confidence interval 5.4 to 16.8. Men engaged in moderate levels of physical activity had a substantially reduced risk of diabetes, relative to the physically inactive men, after adjustment for age and body mass index (0.4; 0.2 to 0.7), an association which persisted in full multivariate analysis. A nonlinear relation between alcohol intake and diabetes was observed, with the lowest risk among moderate drinkers (16-42 units/week) relative to the baseline group of occasional drinkers (0.6; 0.4 to 1.0). Additional significant predictors of diabetes in multivariate analysis included serum triglyceride concentration, high density lipoprotein cholesterol concentration (inverse association), heart rate, uric acid concentration, and prevalent coronary heart disease. These findings emphasise the interrelations between risk factors for non-insulin dependent diabetes and coronary heart disease and the potential value of an integrated approach to the prevention of these conditions based on the prevention of obesity and the promotion of physical activity.
Prospective
study
of
risk
factors
for
development
of
non-insulin
dependent
diabetes
in
middle
aged
British
men
Ivan
J
Perry,
S
Goya
Wannamethee,
Mary
K
Walker,
A
G
Thomson,
Peter
H
Whincup,
A
Gerald
Shaper
Abstract
Objective-To
determine
the
risk
factors
for
non-
insulin
dependent
diabetes
in
a
cohort
representa-
tive
of
middle
aged
British
men.
Design-Prospective
study.
Subjects
and
setting-7735
men
aged
40-59,
drawn
from
one
group
practice
in
each
of
24
towns
in
Britain.
Known
and
probable
cases
of
diabetes
at
screening
(n=
158)
were
excluded.
Main
outcome
measures-Non-insulin
dependent
diabetes
(doctor
diagnosed)
over
a
mean
follow
up
period
of
12
8 years.
Results-There
were
194
new
cases
of
non-insulin
dependent
diabetes.
Body
mass
index
was
the
dominant
risk
factor
for
diabetes,
with
an
age
adjusted
relative
risk
(upper
fifth
to
lower
fifth)
of
11-6;
95%
confidence
interval
5*4
to
16-8.
Men
engaged
in
moderate
levels
of
physical
activity
had
a
substantially
reduced
risk
of
diabetes,
relative
to
the
physically
inactive
men,
after
adjustment
for
age
and
body
mass
index
(0.4;
0*2
to
0.7),
an
association
which
persisted
in
full
multivariate
analysis.
A
non-
linear
relation
between
alcohol
intake
and
diabetes
was
observed,
with
the
lowest
risk
among
moderate
drinkers
(16-42
units/week)
relative
to
the
base-
line
group
of
occasional
drinkers
(0.6;
0
4
to
1.0).
Additional
significant
predictors
of
diabetes
in
multivariate
analysis
included
serum
triglyceride
concentration,
high
density
lipoprotein
cholesterol
concentration
(inverse
association),
heart
rate,
uric
acid
concentration,
and
prevalent
coronary
heart
disease.
Conclusion-These
findings
emphasise
the
inter-
relations
between
risk
factors
for
non-insulin
dependent
diabetes
and
coronary
heart
disease
and
the
potential
value
of
an
integrated
approach
to
the
prevention
of
these
conditions
based
on
the
prevention
of
obesity
and
the
promotion
of
physical
activity.
Department
of
Public
Health,
Royal
Free
Hospital
School
of
Medicine,
London
NW3
2PF
Ivan
J
Perry,
lecturer
in
public
health
medicine
S
Goya
Wannamethee,
statistician
Mary
K
Walker,
research
administrator
A
G
Thomson,
computer
programmer
Peter
H
Whincup,
senior
lecturer
in
epidemiology
A
Gerald
Shaper,
emeritus
professor
of
clinical
epidemiology
Correspondence
to:
Dr
Perry.
BMJ
1995;310:560-4
Introduction
Non-insulin
dependent
diabetes
is
a
common
con-
dition
affecting
at
least
3%
of
the
middle
aged
and
elderly
population
of
Britain,
with
a
considerably
higher
prevalence
in
specific
ethnic
groups.'
Advancing
age,
obesity,
upper
body
fat
distribution,
and
a
family
history
of
diabetes
are
among
the
well
established
risk
factors
for
this
condition.2
Evidence
is
increasing
that
in
some
populations
non-insulin
dependent
diabetes
shares
common
causal
factors
with
cardiovascular
disease
and
in
particular
with
coronary
heart
disease.3
An
inverse
relation
between
physical
activity
level
and
the
risk
of
subsequent
non-insulin
dependent
diabetes
(reported
by
patients
to
have
been
diagnosed
by
a
doctor),
has
been
described
in
prospective
studies
from
selected
populations.s6
Data
on
potential
con-
founding
or
mediating
factors
in
these
studies
have
been
relatively
limited.
Prospective
studies
on
the
role
of
alcohol
in
the
development
of
non-insulin
dependent
diabetes
have
produced
contradictory
findings.79
Cigarette
smoking
has
not
been
extensively
investigated
as
a
risk
factor
for
diabetes.
Smokers
were
at
higher
risk
of
non-insulin
dependent
diabetes
over
25
years
of
follow
up
in
the
Zutphen
study,'0
and
evidence
exists
that
cigarette
smoking
leads
to
insulin
resistance."
Resistance
to
insulin
mediated
glucose
uptake
(insulin
resistance)
antedates
non-insulin
dependent
diabetes'2
and
is
linked
with
dyslipidaemia,
hypertension,
and
several
other
risk
factors
for
coronary
heart
disease.'3
14
We
report
on
a
prospective
study
of
risk
factors
for
non-insulin
dependent
diabetes
among
men
recruited
for
the
British
regional
heart
study.
We
have
focused
on
factors
that
have
been
linked
with
coronary
heart
disease,
such
as
body
mass
index,
physical
activity,
alcohol
intake,
cigarette
smoking,
and
established
biological
risk
factors
for
coronary
heart
disease,
such
as
dyslipidaemia
and
hypertension.
Subjects
and
methods
In
the
British
regional
heart
study
7735
men
aged
40
to
59,
were
selected
at
random
from
the
age-sex
register
of
one
general
practice
in
each
of
24
towns
in
England,
Wales,
and
Scotland
between
January
1978
and
June
1980
for
a
prospective
study
of
cardiovascular
disease.
The
criteria
for
selecting
the
towns,
general
practices,
and
subjects
and
methods
of
data
collection
have
been
described.'5
16
Men
with
cardiovascular
or
other
disease
or
those
receiving
regular
drug
treatment
were
not
excluded.
The
overall
response
rate
was
78%,
ranging
from
70%
to
85%
across
the
24
towns.
Known
diabetic
subjects
(n=
121),
men
diagnosed
within
the
calendar
year
in
which
they
were
screened
(n=
14),
and
those
with
non-fasting
glucose
concentrations
in
the
diabetic
range
(,-
lI
mmol/l,
n
=
23)
were
excluded.
Hence
the
analysis
was
based
on
7577
men.
DATA
COLLECTION:
BASELINE
ASSESSMENT
Research
nurses
administered
a
standard
question-
naire
and
completed
an
examination
of
each
man,
including
electrocardiography."'
The
questionnaire
included
questions
on
occupation,
the
usual
pattern
of
physical
activity,
alcohol
intake,
smoking
habits,
medical
history,
and
use
of
drugs,
including
antihyper-
tensive
drugs.""
Physical
activity-A
physical
activity
score
was
derived,
based
on
the
frequency
and
intensity
of
the
activities
reported.'8
The
men
were
grouped
into
six
physical
activity
categories:
inactivity
(n=
664),
occasional
activity
(n=2282),
light
activity
(n=
1734),
moderate
activity
(n=
1181),
moderately
vigorous
activity
(n=
1104),
and
vigorous
activity
(n=
510).
Data
were
not
available
for
102
men.
Alcohol
intake-The
men
were
classified
into
five
groups
according
to
their
current
alcohol
intake:
none
(n-451),
occasional
(<1
unit/week;
n=1809),
light
(1-15
units/week;
n=2490),
moderate
(16-42
units/
week;
n=
2006)
and
heavy
(>42
units/week;
n=815).
Data
were
not
available
for
six
men.
'9
Cigarette
smoking-The
men
were
categorised
as
those
who
had
never
smoked
(n=
1787),
former
BMJ
VOLUME
310
4
MARCH1995
560
smokers
(n=2649),
and
current
smokers,
(n=3125),
with
the
latter
group
further
subdivided
by
the
number
of
cigarettes
smoked
daily.
Data
were
not
available
for
16
men.'8
Prevalent
coronary
heart
disease-With
the
World
Health
Organisation's
Rose
chest
pain
questionnaire
and
an
electrocardiogram
prevalent
coronary
heart
disease
at
screening
was
defined
on
the
basis
of
any
of
the
following
crtiteria:
recall
of
a
doctor
diagnosing
angina
or
heart
attack,
a
response
to
the
WHO's
Rose
chest
pain
questionnaire
indicating
angina
or
possible
myocardial
infarction,
or
electrocardiographic
evidence
of
definite
or
possible
myocardial
ischaemia
or
infarction.'7
In
all,
24%
(1834)
of
the
men
were
characterised
as
having
prevalent
coronary
heart
disease
at
screening.
This
group
did
not
include
men
who
reported
a
history
of
non-specific
"other
heart
disease."
Body
mass
index
calculated
as
weight
(kg)/(height
(m)2)
was
used
as
an
index
of
relative
weight.
Men
with
a
body
mass
index
of
28
were
categorised
as
obese.
Blood
pressure
was
recorded
with
a
London
School
of
Hygiene
sphygmomanometer.
Two
successive
recordings
were
taken,
and
the
mean
was
used
in
the
analysis
with
adjustment
for
interobserver
variation.
Heart
rate
was
determined
from
the
electrocardiogram.
Non-fasting
blood
samples
were
obtained
between
8
30
am
and
6
30
pm.20
Glucose,
total
cholesterol,
and
uric
acid
concentrations
were
analysed
in
serum
with
an
automated
analyser
(Technicon
SMA
12/60).25-2
Diurnal
variation
in
glucose
concentrations
was
modest,
with
a
peak-trough
difference
of
0
4
mmol/.20
High
density
lipoprotein
cholesterol
and
triglyceride
concentrations
were
measured
with
enzymatic
methods.20
As
triglyceride
concentrations
were
not
determined
for
men
in
the
first
six
towns,
data
on
this
variable
were
available
for
only
5327
men.
<22.9
22.9-
24.6-
26.0-
)27.9
Body
mass
index
(kg/m2)
FIG
1
-Relative
risk
of
non-insulin
dependent
diabetes
(log
scale)
adjustedfor
age
with
95%
confidence
intervals,
by
fifth
of
body
mass
index
relative
to
the
lowerfifth
FOLLOW
UP
FOR
DEVELOPMENT
OF
NON-INSULIN
DEPENDENT
DIABETES
The
men
were
followed
for
morbidity
and
mortality
up
to
December
1991,
a
mean
period
of
12-8
years.22
Less
than
1%
(73)
of
men
were
lost
to
follow
up,
of
whom
44
(0-6%
of
total)
emigrated
from
Britain.
New
cases
of
non-insulin
dependent
diabetes
were
ascer-
tained
by
means
of
(a)
a
postal
questionnaire
sent
to
the
men
at
year
5
of
follow
up
for
each
individual,
(b)
systematic
reviews
of
primary
care
records
in
1990
and
1992,
(c)
a
further
questionnaire
to
6483.surviving
members
of
the
cohort
resident
in
Britain
in
1992,
and
(d)
review
of
all
death
certificates
for
any
mention
of
TABLE
i-Baseline
values
of
selected
variables
(adjusted
for
age
and
body
mass
index)
in
7577
middle
aged
men
initially
free
of
diabetes,
by
incidence
of
non-insulin
dependent
diabetes
dunng
a
mean
follow
up
of
12
8
years
Men
who
did
not
Men
who
develop
diabetes
developed
diabetes
during
follow
up
during
follow
up
Variable
(n-7383)
(n-194)
P
value
From
logistic
regression*:
Manual
occupation
57
56
Current
smokers
41
48
0-06
Moderate
drinkerst
27
20
0
05
Physically
activet
37
28
0.01
Evidence
of
coronary
heart
disease
24
32
0
01
Other
heart
disease
5-9
8-5
Treatment
with
antihypertensive
drugs
4-7
6-7
Any
regular
drug
treatnent
28
32
From
analysis
of
covariance§:
Heart
rate
(beat/min)
70-6
(0-15)
73-2
(0
90)
0
005
Systolic
blood
pressure
(mm
Hg)
145-0
(0-23)
148
2
(1-43)
0
03
Diastolic
blood
pressure
(mm
Hg)
82-2
(014)
8410
(0
90)
0
04
Total
cholesterol
(mmoVl)
6-30
(0.01)
6-34
(0
07)
High
density
lipoprotein
cholesterol
(mmol/l)
1-15
(0
003)
1
11
(0
02)
0
004
Triglyceride
(mmol/l)I
1-73
2-16
<000001
Uric
acid
(,umol/l)
359-1
(0-8)
370
5
(4
8)
0-02
*Values
are
estimated
percentages
of
men
(see
methods
section).
t16-42
Units/week.
tLevel
of
activity
was
moderate
or
higher.
§Values
are
means
(SE)
(see
methods
section).
IlGeometric
mean
(5197
v
130).
diabetes.
The
questionnaire
at
year
5
'achieved
a
response
rate
of
98%22
and
on
the
1992
questionnaire
a
response
rate
of
91%.
A
diagnosis
of
diabetes
was
not
accepted
on
the
basis
of
questionnaire
data
unless
confirmed
in
the
primary
care
records.
STATISTICAL
ANALYSIS
Cox's
proportional
hazards
models
were
used
to
assess
the
independent
contributions
of
the
risk
factors
to
the
subsequent
risk
for
non-insulin
dependent
diabetes
and
to
obtain
the
relative
risks
adjusted
for
the
other
risk
factors.23
Physical
activity
(six
levels),
smoking
(three
levels),
alcohol
intake
(five
levels),
and
pre-existing
ischaemic
heart
disease
(yes/no)
were
fitted
as
categorical
variables
in
the
proportional
hazards
model.
The
adjusted
relative
risks
in
figures
1
and
3
were
obtained
by
fitting
body
mass
index,
systolic
and
diastolic
blood
pressure,
heart
rate,
and
concentrations
of
high
density
lipoprotein
cholesterol,
triglyceride,
and
uric
acid
as
four
dummy
variables
for
the
five
equal
divisions
of
each
risk
factor.
Tests
for
trend
were
carried
out
by
fitting
the
quantitative
variables
in
their
continuous
form.
For
table
I
analysis
of
covariance
was
used
to
derive
the
means
adjusted
for
age
and
body
mass
index,
and
logistic
regression
was
used
to
calculate
prevalences
adjusted
for
age
and
body
mass
index
on
the
basis
of
conversion
of
adjusted
odds
ratios
to
estimated
proportions.
For
tables
II
and
III
the
validity
of
the
proportional
hazards
assumption
in
Cox's
models
was
checked
by
fitting
a
time
dependent
interaction
variable
x=x(t),
where
x(t)=log(t).
Subjects
with
missing
values
for
covariates
in
the
various
adjustments
with
Cox's
model
were
excluded
from
that
particular
analysis.
As
glucose
and
triglyceride
concentratioris
were
not
normally
distributed
log
transformation
and
geometric
means
were
used.
Because
of
the
pronounced
diurnal
variation
in
serum
triglyceride
concentrations20
the
log
transformed
data
on
this
variable
were
adjusted
for
time
of
sampling.24
Results
After
a
mean
follow
up
period
of
12-8
years
there
were
194
new
cases
of
non-insulin
dependent
diabetes
in
the
7577
men,
an
incidence
of
2-
15
per
1000
person
years
of
follow
up.
Men
who
developed
diabetes
had
significantly
higher
mean
blood
glucose
concentrations
at
screening
than
those
who
remained
free
of
diabetes
(6-2
v
5-4
mmolIl;
P<0-0001).
Little
difference
in
mean
age
existed
between
the
two
groups
(50
4
v
50
2).
Those
who
developed
diabetes
had
a
significantly
higher
mean
body
mass
index
than
those
who
did
not
(27-9
v
25-4;
P
<
0
0001).
Forty
four
per
cent
(85/194)
of
the
men
who
developed
diabetes
were
obese
(body
mass
index
of
3
28)
compared
with
18%
(1328/7383)
of
those
who
did
not.
The
risk
of
non-insulin
dependent
diabetes
increased
exponentially
with
increasing
body
mass
index,
with
an
over
11-fold
excess
risk
in
the
upper
fifth
(>,
27
9)
relative
to
the
lower
fifth
(
S
22
9-)
(relative
risk=
11-6;
95%
confidence
interval