Physical activity promotion in the primary care setting in pre- and type 2 diabetes

Main objective

The main objective of Sophia Step Study is to evaluate the impact of a multi- component
and a single-component primary care physical activity intervention aiming at improving
HbA
_1c
(primary outcome) and other metabolic and cardiovascular risk factors, physical activity
levels and overall health in patients with pre-diabetes and type 2 diabetes.

Hypothesis

The hypothesis is that both levels of intervention have effect on the primary outcome
HbA
_1c
, with the multi-component intervention having superior and longer lasting effects.

Study design and recruitment

The Sophia Step Study is a two-year randomized controlled trial (RCT) with three parallel
groups. The CONSORT statement is followed 45]. The study takes place at the primary health care centers at Sophiahemmet, Stockholm,
Sweden.

All patients at the health care centers diagnosed with pre-diabetes and type 2 diabetes
and fulfilling the inclusion criteria are informed of the study and asked whether
they are interested in participating (Fig. 1). Patients showing interest receive a letter with further information and are subsequently
interviewed over telephone by the diabetes specialist nurse and asked a set of inclusion/exclusion
questions. If they fulfil the inclusion criteria they are booked for a baseline control.

Fig. 1. Recruitment procedure and randomization of Sophia Step Study subjects

Inclusion criteria

Age 40-80 years and ability to communicate in Swedish. Either Pre-diabetes (HbA
_1c
??39-??47 mmol/mol and/or fasting glucose 5.6 mmol/l) or diagnosed with type 2
diabetes with a duration of ?1 year.

Exclusion criteria

Myocardial infarction in the past 6 months, serum creatinine 140 mmol/l, diabetic
foot ulcer or risk of ulcer (severe peripheral neuropathy), on insulin since the last
6 months, additional disease prohibiting physical activity, repeated hypoglycemia
or severe hypoglycemia in the past 12 months, being very physically active according
to the Stanford Brief Activity Survey 46] or having no access to internet.

Procedure and timeline

The baseline measurements start with an examination by the patient’s general practitioner
for exclusion purposes. A notification is made on subjects not fulfilling the criteria
at this stage. The study-specific measurements are made by the diabetes specialist
nurse or a trained assistant, followed by randomization to three groups using closed
envelopes while stratified by gender. The participants are randomly assigned to either
the multi-component intervention group (A), the single component group (B) or a control
group (C). A total of 310 patients with pre- diabetes or type 2 diabetes will be included
gradually, with the aim of 100 participants included in group A and B, and 110 in
the control group C by the end of 2017. After randomization, participants are given
a schedule for measurement time points and group A participants receive a schedule
for group sessions and individual consultations. The intervention lasts for 24 months,
with more intensive support from the health care professionals within the first 24
weeks, and less support in the second year (Fig. 2).

Fig. 2. Time frame for Sophia Step Study. Time points for intervention components (grey) and
data collection (black) for all groups. *Including blood samples, anthropometric and
physical activity measurements and questionnaires. More details are depicted in Table 1

Sophia Step Study started with a pilot group in March 2013, entailing 8 participants
in group A and 6 in group C. The pilot revealed compliance to the protocol and ability
to recruit and the first participants were recruited in November 2013. The plan is
to have 310 participants completed the intervention in 2020.

Intervention

Pedometer

In week 1, participants in the intensive intervention group (A) and the pedometer
group (B) arrive for their second visit at the health care center. They are offered
a pedometer (YAMAX; model Yamax Digiwalker SW 200: Yamax Corporation, Tokyo, Japan),
instructions for how to use the pedometer, how to record their daily steps and to
set a daily step goal on a website (www.steg.se, Select Wellness AB, Stockholm, Sweden). The participants register steps daily in
a diary, and are recommended to enter them onto the website weekly. Non-ambulant activities
such as biking and swimming are translated into steps by a simple calculation (each
30 min of activity, regardless of intensity, gives 3500 steps). On the website a “healthy
goal” of minimum 7000 step per day is depicted as a reference 47]. The participants are asked to decide on individual goals after the first week of
wearing the pedometer. If a pedometer stops working or gets lost the participants
are encouraged to pick up a new pedometer at the health care center or a new pedometer
is sent by post.

Group counseling

Group A participants are offered 12 group meetings (Fig. 2) over two years’ time, with the majority of meetings being held in the first six
months. The group meetings include a 30 min walk and 60 min group consulting and are
steered by a health professional trained in physical activity promotion and familiar
with models and techniques for behavior change. A workbook developed for the project,
based on the Health Belief Model, the Stages of Change Model and Social Cognitive
Theory is used. The content of the group counseling program and the behavior change
techniques used is shown in Fig. 3. The order of the content may shift depending on holidays, season or other concerns
that arise.

Fig. 3. Group counseling program for group A with the content and the behavior change techniques

Person-centered individual counseling

Group A participants are offered individual consultations with their diabetes specialist
nurse at 9 occasions. The nurses are trained in MI and are using an MI-spirit in their
consultations. The consultation takes place concurrently with the study measurements
and the health outcomes from the measurements and the number of steps taken recently
serves as a basis for these talks. Moreover, the nurse is, during one of the first
MI-talks prescribing physical activity according to the method FaR 35]. The nurse also informs participants about the opportunities that follow a prescription,
such as subsidies to gyms and sport clubs and trained staff at certain sport clubs.
The prescription is followed up yearly. All in all, the meetings take 45-60 min each.

Usual care

The control group (C) receives diabetes care as usual, except for the extra measurements
included in the study. Usual care consists of seeing a diabetes specialist nurse and
a general practitioner at least once a year and receiving lifestyle advice, including
advice on physical activity. Depending on the metabolic status of the patient there
might be consultations with both the nurse and/or the general practitioner more often.
The number of consultations made will be recorded for each participant. A physical
activity prescription might also be issued as a part of usual care, but not in a systematic
way.

Theoretical framework

It is widely recommended that program design should be based on a theory and the behavior
change techniques used should be depicted to improve evidence synthesis 21], 43], 48]. The theoretical framework underpinning the two interventions in Sophia Step Study
is the Health Belief Model, the Stages of Change Model and the Social Cognitive Theory
49]. Both the multi-component intervention (group A) and the pedometer intervention (group
B) are using several behavior change techniques based on the CALO-RE taxonomy 48].

Based on these theories various intervention components were chosen to offer flexibility;
to adjust to individual differences and preferences and to strengthen change. A conceptual
framework visualizing the intervention program is depicted in Fig. 4.

Fig. 4. Conceptual framework of Sophia Step Study. The conceptual framework depicts the underlying
theories, the intervention components with the behavior change techniques used and
the expected outcomes for the two intervention groups

Outcome measures

Measurements are made on all participants at week 0, 8, 12, 16, 24, month 9, 12, 18
and 24. The primary outcome variable is HbA
_1c
. Health outcomes and measurement time points are summarized in Table 1. The measurements are planned to be performed within?±?2 weeks and notes are made
if they are made sooner or later than this.

Table 1. Outcome parameters and time points for measurements for all groups in Sophia Step
Study

Biomarkers

Measurements include fasting blood samples on HbA
_1c
(mmol/mol), plasma glucose (mmol/l), triglycerides (mmol/l), LDL (mmol/l), HDL (mmol/),
total Cholesterol (mmol/l), free fatty acids (mmol/l), Insulin (mU/l), IGF BP1 (?/l), Apolipoprotein-A1
(g/l), Apolipoprotein B (g/l) and C-peptid (nmol/l). HbA1c, haemoglobin A1c (ref??5.2
%) is determined with immunologic MonoS method, Unimate (Roche Diagnostics, Basel,
Schweiz). To convert HbA1c MonoS into HbA1c (DCCT) NGSP (National Glycoprotein Standardization
Programme) the formula, NGSP?=?0.92*MonoS?+?1,33 is used. Plasma glucose are determinedwith
a glucose oxidase method, total Cholesterol and triglycerides are determined by using
enzymatic method, LDL and HDL are determined by using a homogeneous method, Apolipoprotein-A1
and Apolipoprotein B are determined by using turbimetric method and C-peptid are determined
by using immunometric method using two monoclonal antibodies and detection with electrochemiluminiscense
using a Modular E system (Beckman Coulter, Inc.). Serum insulin concentrations are
determined with RIA-kits purchased from Pharmacia Upjohn, Stockholm. IGFBP-1 concentrations
in serum are determined by RIA according to the method of Póvoa et al. 50]. Samples are saved for later free fatty acid analyses.

Anthropometry

Anthropometric measurements include weight and percentage body fat using Tanita digital
scale (Model TBF-300A, Arlington Heights, IL). Weight is measured with light clothes,
no shoes to the nearest 0.1 kg. Height is measured at the first visit by use of a
calibrated stadiometer to the nearest centimeter. Waist circumference is measured
with SECA 201 tape, horizontal around the waist 2 cm above the umbilicus. Sagittal
abdominal diameter is measured with the subject in a supine position with the knees
expanded at the level of the umbilicus using a Holtain-Kahn abdominal caliper (Holtain,
Ltd., Crosswell, Crymych; Dyfed, UK). Resting pulse and blood pressure is measured
with Omron M6 Comfort.

Objectively measured physical activity

To objectively assess total physical activity as well as sedentary time and time spent
in different intensities the ActiGraph GT1M accelerometer (ActiGraph, Pensacola, FL)
will be used. The participants are asked to wear the accelerometer placed on the back
all wakening hours for seven consecutive days. The accelerations are sampled at 10
Hz i.e. 10 times per second and data is summarized over one minute and outputted as
numerical counts. Total physical activity is expressed as total counts and steps per
day. Time spent sedentary and in different intensities is derived from established
cut-points according to Freedson (1998) and Matthews (2005 and 2008) 51]–53].

Resistance training

Initiation of regular resistance training is reported contemporary with the measurement.
Hand grip strength is measured as a proxy for overall muscle strength 54]. Hand grip strength is measured in kilograms using the hand-held Saehan Hydraulic
Hand Dynamometer, model SH5001 (former Jamar) (Saehan Corporation, Masan, South Korea).

Questionnaires

A web-site delivered questionnaire is e-mailed to the participants at baseline, week
12, and at 6, 12 and 24 months. The questionnaire takes 30-40 min to complete, incorporates
several validated questionnaires and some study specific questions including demographic
and lifestyle characteristics that aims to evaluate diet, physical activity, motivational
circumstances to be physically active, overall health and well-being and problem areas
in diabetes.

Demographic data are collected by study specific questionnaire with items on civil status, having
children under 18, caring for relatives, educational level and income.

Smoking and snuffing habits are measured using questions on current and previous habits and the dose.

An indication of dietary habits is measured by a Food Frequency Questionnaire (FFQ) developed and validated by The
Swedish National Food Agency. This questionnaire is recommended to use in Swedish
populations for its validity and reproducibility and for comparable reasons 55].

Drinking habits are assessed by two items based on the amount and regularity of alcohol consumption
56].

Stress and working conditions are measured by 4 items on over-time, paid overtime, having subordinates and perceived
work security.

Health outcome is measured using The EuroQol (EQ-5D 3L) that includes questions on mobility, hygiene,
daily activities, pain/ discomfort and anxiety/depression. Within the particular EQ-5D
dimension the responses are within three levels of severity; no problems, some or
moderate problems and extreme problems. The questionnaire also measures overall health
status on a vertical visual analogue scale where 0 indicates worst imaginable health
and 100 best imaginable health 57]. An approval to use the instrument in the current project is received from The EuroQol
group.

Overall health and sleep is measured by a 1-100 scale for health condition where 0 is worst possible and 100
is best possible. One question on difficulties falling asleep and one question on
sleep quality.

Subjectively assessed physical activity is measured with The International Physical Activity Questionnaire (IPAQ), a self-administered
7-item questionnaire that evaluates the frequency and duration of walking, moderate-
and vigorous-intensity physical intensity, and minutes spent sitting during the past
week 58].

Social support for exercise is measured with Physical Activity Social Support (PASS) first developed by Sallis
et al. 59]. The PASS examines general support (1 item), friend (2 items), family (2 items) and
colleagues support for exercise. PASS is using a 4-point Likert response scale (1?=?strongly
agree to 4?=?strongly disagree).

Self-efficacy for exercise is measured with the 5-item scale The Self-Efficacy for Exercise Scale. It assess
one’s confidence to continue exercising when feeling tired, being in a bad mood, not
having time, being on vacation and at bad weather 60].

Neighborhood environment is assessed by the scale Neighborhood Environment developed by Mujahid et al., 2007
and using a 5-point responses (1?=?strongly agree to 5?=?strongly disagree) 61]. In this study 17 items about abilities to undertake exercise and walking, availability
of foods, safety and social environment are used.

Depression and anxiety is measured with The Hospital Anxiety and Depression Scale (HADS): HADS is a 14 item
questionnaire consisting of two subscales; depression and anxiety, with seven items
each. The items are graded on a four-point Likert scale ranging from 0-3. The total
score ranges from 0-21 for the HADS depression scale and ranges from 0-21 for the
HADS anxiety scale 62].

Stress is measured with The Perceived Stress Scale (PSS) which is a 14- item questionnaire
used to measure how stressful different situations in one’s life are perceived (Cohen
et al. 1983). The items are graded on a five-point Likert scale. The total score for
PSS ranges from 0-56. Eskin et al., 1996 have psychometrically tested the Swedish
version of PSS 63].

Diabetes distress is measured using The Problem Areas in Diabetes questionnaire (Swe-PAID-20): This
is a 20 items questionnaire translated in to Swedish by Amsberg et al. 64]. The patient rates their distress with having diabetes on a five-point Lickert scale,
from 0 = not a problem to 4?=?serious problem. The total score ranges from 0-100.
The original version of PAID was developed by Polonsky et al., 1995 65]. These questions are only answered by the participants diagnosed with diabetes.

Fidelity criteria

Attendance and notes on reasons for absence at individual visits and group consultation
is made after each session. Compliance to registration of steps is made monthly and
reasons for failing to register steps is tracked and noted. Notes from the MI talk
are registered in the health journal. The project group has regular meetings to discuss
issues regarding MI talks, physical activity on prescription and measurements, in
order to assure the routines of both measurements and intervention components. The
quality of each individual counseling session is assessed on a 1-10 scale by the diabetes
specialist nurse for both motivational interviewing and physical prescription. A qualitative
study to explore how the participants perceived the support as well as barriers and
facilitators will help to evaluate the intervention efficacy from a patient perspective.

Sample size and planned statistical analysis

The sample size calculation assumed 80 % power and was calculated drawing on previous
literature 14], 66] by statistical power analysis. To detect a difference of??0.6 mmol/mol in HbA
_1c
with a standard deviation of 1.2 % at 12 months between group A and B and between
group A and C we need 56 per group. Taking account the compliance and drop-out (30
%) and patients which decline participation (20 %) we need in group A 100 patients,
in group B 100 patients and in group C 110 patients.

The study will be evaluated with both quantitative and qualitative methods and a cost-effectiveness
analysis will be performed. The CONSORT 2010 statement will be used for description
and analysis 45]. Data will be analyzed following the Intent-to-treat approach (ITT). Descriptive
statistics will be used to describe the study population at baseline. The study data
will be examined for outliers, normality and missing data. Potential confounders as
(e.g. BMI at baseline, gender and age) will be used if there are differences at baseline.

Un-paired and paired tests, correlation coefficients as well as ANOVAs will be used
to assess the bivariate effects of the interventions and to analyze within-group and
between-group differences and changes. In addition, logistic regression models and/or
cluster analyses will be performed to analyze issues related to dose–response and
responder characteristics. SPSS 22 (SPSS Inc., Chicago, IL, USA) will be used for
the statistical analysis.

Limitations

Individuals with pre-diabetes and diabetes are randomized in the same group and it
can be discussed whether the same decline in HbA
_1c
can be expected in individuals with pre-diabetes. Furthermore the participants in
the control group may be influenced by participating in a research study and being
assessed regularly. As they agree to join they are highly motivated to change their
physical activity level and we expect many of them to succeed in this by their own.
This could make comparison of between-group differences problematic. Moreover, the
control group is assessed by the same staff as group A and B, for practical and financial
reasons. This staff is trained in motivational interviewing and it might be difficult
to treat the patients differently. At measurements participants from group A, B and
C are given different schedules, group A participants are offered more time and a
systematic motivational interviewing following a set of questions.