Progression From Impaired Fasting Glucose to Diabetes Mellitus Clinical Trial
Official title:
Determinants of Progression From Impaired Fasting Glucose to Diabetes Mellitus Among Chinese - a 3-year Follow up Study
Impaired fasting glucose (IFG), a significant risk factor for diabetes mellitus (DM), is
commonly encountered in the primary care setting and represents an important target for DM
prevention. However, data on the long term risk of progression from IFG to DM among Chinese
subjects and associated risk factors are currently lacking; appropriate DM prevention
programme for this group cannot be yet established.
This is a prospective cohort study that aims to estimate the incidence of progression to
diabetes mellitus (DM) among Chinese primary care patients with impaired fasting glucose
(IFG) over a 3-year period and evaluate putative risk factors. A prospective cohort of around
700 non-diabetic Chinese adults who had IFG (i.e. fasting glucose level between 5.6 to
6.9mmol/L) and received baseline assessment between May 2013 and March 2015 at 3 public
primary care clinics across Hong Kong will be invited for a 36-month-follow-up glycaemic
status assessment (i.e. to repeat 75-gram oral glucose tolerance test (OGTT) and HbA1c test).
The OGTT results will be used as the gold standard for the diagnosis of DM, normoglycaemia,
IFG and impaired glucose tolerance (IGT) state. Demographics and lifestyle of the subjects
including age, gender, occupation, education level, socio-economic status, smoking and
drinking history, diet, exercise, work-sleep pattern, stress, quality of life and family
history will be collected using standardized questionnaire. Participant's medical history and
drug history will be retrieved from the Clinical Management System (CMS) of the Hospital
Authority. Lipid profile, blood pressure, waist circumference and body mass index will also
be assessed.
Logistic regression model will be performed to determine if these variables are associated
with progression from IFG to DM. The primary outcome is the incidence of DM among the IFG
study population. The secondary outcomes are the risks of developing DM among subjects with
isolated IFG or combined IFG/IGT and determinants of progression to DM.
Knowledge on the natural history of isolated IFG or combined IFG/IGT among Hong Kong Chinese
primary care patients and the significant modifiable associated risk factors for progression
to DM will enable primary care researchers to design optimal management programme for
diabetes prevention among these high risk patients.
Impaired fasting glucose (IFG) represent an intermediate state of abnormal glucose regulation
that exist between normal glucose homeostasis and diabetes mellitus (DM) and is a significant
risk factor for DM and cardiovascular complications. IFG is defined by an elevated FG level
between 6.1-6.9mmol/L according to the World Health Organization (WHO). The lower cutoff
level for IFG was further lowered to 5.6mmol/L by the American Diabetes Association (ADA) in
2003 in order to maximize sensitivity and specificity for predicting DM over a 5-year period.
In Hong Kong, IFG individuals can be more readily identified by primary care doctors than
subjects with impaired glucose tolerance (IGT) or elevated HbA1c - the other 2 pre-diabetic
categories - because fasting glucose (FG) test is recommended by the Hong Kong reference
framework for diabetes care for adults in primary care setting for DM screening. Thus, this
group of individuals should be targeted opportunistically for DM prevention.
On the other hand, IFG is a heterogeneous group with variable risk of progression to DM.
Individuals with IFG may have concomitant IGT, elevated HbA1c or even DM. Thomas et al. found
that around 20% of Hong Kong Chinese subjects with impaired glucose relation had concomitant
IFG and IGT, whereas 49.5% had isolated IGT and 30.5% had isolated IFG. Ko et al. followed up
55 Chinese subjects with IFG for a median period of 1.12 year and showed that 8.4% progressed
to DM annually as defined by fasting glucose criteria (FG ≥7.0mmol.L). Lee et al. followed up
238 Chinese women with persistent impaired glucose tolerance after gestational diabetes over
a mean period of 52 months and found that 20% of the studied population developed diabetes
mellitus based on OGTT criteria; the highest rate of progression to DM was noted among those
women with concomitant postpartum impaired fasting glucose.
A recent cross-sectional study by Yu et al on 1,200 Chinese primary care patients with IFG
demonstrated that 20% had DM confirmed by OGTT as the gold diagnostic standard, 14.3% had
concomitant IGT, and 16.1% would regress back to normoglycaemia upon retest within 18 months.
However, all of these local studies had short follow-up period and used different diagnostic
tests for confirmation of DM; the long term risk of progression to DM among Chinese subjects
with isolated IFG or combined IFG-IGT had not been fully evaluated.
Moreover, only few studies examined the risk factors for progression from IFG (+/- IGT) to DM
among Asians or Chinese. Female gender, smoking, low physical activity, obesity as well as
truncal obesity, high blood pressure, high triglyceridaemia and most importantly higher
baseline FG level had all been reported to increase risk of progression from IFG to DM among
Caucasians. In the only Asian study conducted in Japan, Toshihiro et al. found that stress in
daily life, night duty and administrative position were risk factors of DM development among
IFG subjects. To the best of our knowledge, no published data on the risk factors of
progression from IFG to DM among Chinese is currently available. It was not certain that the
risk factors identified among the Caucasians or Japanese were applicable to the Chinese.
Although intensive lifestyle modifications targeting these risk factors had been reported to
reduce progression from IFG to DM, their effects on Chinese subjects with IFG had not been
evaluated.
Between May 2013 and March 2015, our team have already collected a prospective cohort of
around 700 non-diabetic adults who have underwent both 75g OGTT and HbA1c tests as rigorous
determination of their glycemic status. We aim to conduct a 3-year follow-up study to
estimate the incidence of progression to DM among Hong Kong Chinese primary care patients
with IFG with or without concomitant IGT using OGTT as the gold diagnostic standard as
recommended by the Hong Kong Reference Framework. In addition, we aim to identify
determinants, in particular the modifiable risk factors, for the progression from IFG to DM.
These results will provide valuable information for designing optimal follow-up plan and
diabetes prevention programme for local IFG patients, with the ultimate goal to reduce health
care burden of DM on our society.
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