The New Hoorn Study - prevalence and determinants of impaired glucose regulation

Prevalence and determinants of impaired glucose regulation
In 1989 a large study on the prevalence of type 2 diabetes (DM2) and impaired
glucose tolerance (IGT) in the general population of the Netherlands was
performed (The Hoorn Study). Results showed that the prevalence of DM2 and IGT
(assessed with an OGTT) in 2484 participants aged 50 to 75 years was about
20%. Age, family history of diabetes and waist-to-hip ratio (WHR) were the most
important determinants of glucose metabolism.
Due to various lifestyle and demographic changes, the prevalence of DM2
increased worldwide. In addition, these changes have led to a change in the
phenotype of DM2. Despite these changes, no large population-studies aimed to
determine the prevalence of impaired glucose regulation and determinants of DM2
in the Netherlands have been carried out in the last 15 years.
Beta-cell function in the general population.
Beta-cell dysfunction is the key component of hyperglycaemia in the aetiology
of DM2. Research has been done on beta-cell function in subgroups with impaired
glucose regulation or in small (ethnic) cohorts of the general population, but
little is known about (determinants of) beta-cell function in the general adult
population, assessed with a large cohort study.
Mental well-being
The prevalence of depression is twice as high in individuals with DM2 than in
those without, but the causes of the high prevalence of depression in DM2 are
unclear. Depression and other mental well-being related aspects (anxiety, mood
disorders, somatisation) are indicators of stress. The evidence suggesting a
relationship between psychosocial stress and the pathophysiology of glucose
intolerance and CVD is accumulating. A possible mechanism is the disturbance of
the autonomic nervous system balance, but more research is needed to establish
this.

A. To determine prevalence and determinants of impaired glucose regulation
1. To study the prevalence of impaired glucose regulation and type 2 diabetes
in the general population aged 40 to 65 years, and to compare these prevalence
rates with those in the first Hoorn Study (1).
2. To study differences in various anthropometric and metabolic population
characteristics (with special attention to lifestyle factors and body
composition) between subgroups with a different glucose status.
3. To study differences in various indicators of cardiovascular disease (i.e.
intima media thickness (IMT), cardiovascular risk profile, microalbuminuria,
insulin resistance, hyperinsulinemia) between subgroups with a different
glucose status.

B. To study beta-cell function in the general population
4. To study the distribution of insulin secretion and insulin sensitivity, as
assessed by modelling of glucose and insulin concentration during a 75 g OGTT
in the general population.
5. To study the (cross-sectional) association of various anthropometric and
metabolic characteristics with beta-cell function in the general population.

C. To study mood disorders in subgroups with a different glucose status
6. To study the (cross-sectional) association between mood disorders and
glucose status.
7. To study the role of autonomic nervous system balance in the association
between mood disorders and glucose status.

The study is designed as a observational cohort in the general population.
A random sample of 5000 men and women, aged 40-65, will be drawn from the
municipal registry of Hoorn, in order to include 3000 individuals (expected 60%
inclusion rate).
The subjects will be invited in sub cohorts based on postal code (district) and
will be asked to bring two visits to the Diabetes Research Center in Hoorn. The
first visit is a relatively short visit aiming to include as many participants
as possible in the study, after which a second (longer) visit will be
scheduled. Following Dutch privacy legislation, all subjects are written on
behalf of the municipality, with a description of the study, and the request to
return a form with their name, address and telephone number (appendix 1). When
subjects do not return the form within two weeks, a reminder will be sent
(appendix 2).
After receiving the form, the investigators can contact the participants to
check the exclusion criteria and schedule an appointment. The appointment made
by telephone will be confirmed with a letter in which date and time and
instructions to follow prior to visit 1 will be mentioned (appendix 3).
When all participants have visited the Diabetes Research Center for visit 1,
appointments will be scheduled for visit 2. Time between visit 1 and 2 is
expected to be about one year.
Subjects may withdraw at any time from the study without providing a reason.


Participants will bring two visit to the Diabetes Research Center in a fasting
state

Visit 1
In- and exclusion criteria will be checked and informed consent will be
obtained. Anthropometry (height, weight, waist circumference and hip
circumference) and blood pressure measurement will be performed.
A 2-point Oral Glucose Tolerance Test (OGTT) , with blood draws at 0 en 120
minutes after glucose ingestion will be performed. Blood samples of both time
points will be used for determination of glucose.
Habitual physical activity (SQUASH), food consumption (Voedselvragenlijst,
Universiteit Wageningen), smoking, alcohol intake, employment, education,
marital status, current medication use, disease history, family history of
disease, depression (CES-D), anxiety (HADS), perceived general health (SF-12),
and self-reported birth weight will be determined using questionnaires.

Visit 2
To estimate beta-cell function, a 7-point OGTT will be performed. Two fasting
blood samples will be taken before the OGTT (t=-15 and 0), afterwards blood
samples will be taken at 15, 30, 60 and 120 minutes. Blood samples of all time
points will be used for determination of C-peptide, insulin and glucose. In
addition, from the fasting blood sample, high sensitive CRP (CRP-hs, marker for
low-grade inflammation), triglycerides, and total and HDL-cholesterol (markers
for lipid metabolism) will be determined.
The standard 12-lead electrocardiogram will be recorded and the ankle-brachial
index and carotid intima media thickness (IMT) will be determined as measures
of prevalent cardiovascular disease. Measurements of heart rate variability
will be made to estimate autonomic nervous system balance.
A sample of first void morning urine is requested for determination of
microalbuminuria, as a marker for endothelial function (cardiovascular risk).

Patients need to visit the Diabetes Research Center in Hoorn twice in a fasting
state. The first visit will take about 2,5 hours, the second visit about 5
hours.


There are 3 aspects to this protocol that may cause some discomfort to the
subjects. First, the subjects have to abstain from heavy physical activities
(e.g. sports) 48-h prior to the visits and remain fasted as indicated. Second,
subjects may suffer from an unpleasant feeling of nausea during the OGTT (this
might happen in about 1 in 60 people). This reaction should subside within 15
minutes to 1 hour. Third, the collection of blood may cause some discomfort.
Possible side effects from blood drawing include faintness, inflammation of the
vein, pain, bruising, or bleeding at the site of puncture. There is also a
slight possibility of infection.
Benefits are that we will be albe to detect diabetes in an early stage, which
gives the oppertunity for early treatment.