A Cognitive Behavioral Intervention to Reduce Fear of Hypoglycemia in Young Adults With Type 1 Diabetes
Phase: NA
Conditions: Type1diabetes
Sponsor: University of Illinois at Chicago

 
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PROTOCOL 
A Cognitive Behavioral Therapy Intervention (FREE) to Reduce Fear of Hypoglycemia in Young Adults 
with Type 1 Diabetes 
1.        ABSTRACT    
In persons with type 1 diabetes (T1DM), iatrogenic hypoglycemia is the major limiting factor in achieving 
optimal blood glucose control. All persons with T1DM are at risk for hypoglycemia (blood glucose level < 70 
mg/dl), which is life-threatening and has serious physical symptoms and psychological sequelae that lead to 
profound fear of future hypoglycemic events. This fear results in greater glucose variability (the intra-day 
fluctuations in blood glucose), due to under- or overcompensation of food intake, insulin dosing, or physical 
activity, as well as anxiety, depression, and reduced quality of life. Greater glycemic variability (GV) is 
associated with a higher risk of hypoglycemia and diabetes complications. Young adults are particularly at risk 
because they report greater FOH and have poorer glycemic control. A major gap exists in how to manage FOH 
as a crucial component of diabetes self-care. Our overall objective is to reduce FOH and improve diabetes self-
management, glycemic control, and variability in young adults with T1DM.  We specifically aim to: (1) 
Determine the feasibility of an 8-week CBT-based intervention to reduce FOH and (2) obtain means and 
standard deviations of group differences from baseline to program completion on the outcomes of FOH, self-
management, glycemic control and glycemic variability in young adults with T1DM who experience FOH. To 
achieve these aims, we propose a randomized control pilot trial in 10 young adults aged 18 to 30 years with 
T1DM. Participants will be screened for FOH levels. Eligible subjects will be randomized to the intervention 
(Fear Reduction Efficacy Evaluation [FREE]) program or attention control group. A 1-week run-in phase is 
planned, with baseline measures of FOH and 24-hour real-time continuous glucose monitoring recordings (RT-
CGM) to calculate GV for both groups. The intervention group will participate in eight weekly one-hour 
sessions using a cognitive behavioral therapy (CBT) and exposure treatment for specific fears. RT-CGM and a 
daily FOH diary will be used as feedback cues. The control group will wear a 24-hour RT-CGM device during 
the same 8-week period and return for weekly RT-CGM site changes by study staff. At completion, FOH will be 
measured, and RT-CGM recordings will be analyzed to determine within-group and between-group 
differences. The findings from this proposed study will serve as the foundation for a larger clinical trial to 
reduce FOH and improve self-management, glycemic control, and variability. Meeting these goals will have 
important clinical implications to reduce diabetes complications and improve quality of life in young adults with 
T1DM.  
 
  
2.         RESEARCH PLAN 
 
B. Specific Aims  
The specific aims of this IRSP pilot study are:  
1. Determine the feasibility of the 8-week fear reduction intervention FREE in young adults with T1DM 
who report FOH. Feasibility will be determined through analysis of recruitment, retention, and 
participant evaluation.  
2. Obtain means and standard deviations of within-group and between-group differences from baseline 
to program completion (8th week) and post-program (12th week) on the outcomes of FOH, self-
management, glycemic control (A1C), and GV. This data will be used for calculation of effect sizes for a 
future larger study.  
C. Research Strategy 
1. Significance 
Why focus on FOH in young adults? Despite refinements in insulin therapy and advancements in 
glucose-sensing technology over the past several decades, fear of hypoglycemia (FOH) remains a critical 
deterrent to T1DM self-management, psychological well-being, and quality of life (QOL).15 Fear is 
conceptualized as an emotion arising from a cognitive appraisal of a specific threat or danger.20 Normal fear is 
adaptive, stimulating more vigilance and improved performance; whereas heightened fear leads to increased 
anxiety and may result in a delay to action or inappropriate action.19,20,21 Anxiety may mimic the symptoms of 

 
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hypoglycemia and impair its detection, further complicating the problem.5,22 At the extreme, fears can develop 
into anxiety disorders and phobias.7,19,23 Young adults experience higher FOH levels than adolescents and 
middle-aged adults;15 thus, it is critical to develop strategies to assist young adults in coping with FOH. 
Previous negative experiences of hypoglycemia influence health behaviors used in diabetes self-management, 
including insulin dosing, dietary patterns, and physical activity.10,15,24-28 Insulin doses may be inappropriately 
reduced in anticipation of hypoglycemia, and diet may be modified to avoid hypoglycemia. Dietary 
modifications may include excessive eating, particularly more carbohydrates11,29 or snacking at night.27,30 
These excessive modifications lead to increased GV.  
Over the past three decades, a number of newer technologies have been designed to help patients with 
diabetes manage their treatment regimens, including continuous glucose monitoring (CGM) systems, insulin 
pumps, sensor-augmented pump therapy with threshold suspend features, and insulin bolus calculators. While 
these devices have improved glucose control (i.e., A1C), improved glucose control has not consistently 
translated into reduced FOH.31-37  
What has been used to address FOH? Diabetes education programs typically discuss FOH but have not 
developed strategies to manage it.4 Education, motivational interviewing, and cognitive behavioral therapy 
(CBT) interventions have been developed to improve glucose control,38-40 but no program has been 
established to specifically address FOH. Improved glucose management has had variable effects on FOH.4,39-
45 Outcomes have demonstrated that, as glucose levels are lowered, worry levels have not consistently 
decreased,38 and any improvements that have occurred have not been sustainable.4 We hypothesize that the 
lack of consistent and sustainable reductions in FOH has occurred because the focus of these programs has 
been on glycemic control, not on FOH. Any strategy that focuses on managing glucose to near-normal levels 
must include methods to cope with the fear that lower blood glucose levels could lead to hypoglycemia. FOH 
management must be a part of diabetes care.46 A fear reduction program, informed by the proposed study, 
may provide a more comprehensive approach to diabetes care that reduces anxiety and improves glycemic 
control and variability. 
Why is glycemic variability (GV) important? Lower hemoglobin A1C levels are associated with a 
reduction in microvascular complications.47 Although A1C provides a biomarker for average blood glucose over 
a 2- to 3-month period, it does not capture daily blood glucose level fluctuations that occur. Evidence supports 
the role that GV (daily fluctuation) plays in the generation of oxidative stress,14 endothelial dysfunction,48 and 
diabetes complications in T1DM.49 High degrees of GV are associated with more frequent episodes of 
hypoglycemia12 and fluctuations between glucose extremes (i.e., hypo- to hyperglycemic levels), which may 
occur with overtreatment of a hypoglycemic episode. GV is directly influenced by self-management behavior50 
and is amenable to change with appropriate intervention.  
Why use a cognitive behavioral approach (FREE) to reduce FOH? Increased FOH creates anxiety, 
which may impair awareness of internal and external blood glucose cues and leave individuals less prepared 
to take action.19 Heightened fear may develop due to previous negative hypoglycemic thoughts, feelings, and 
experiences that create a conditioned negative response to future fear triggers.19,51 An approach that uses 
cognitive behavioral techniques such as cognitive restructuring, exposure to feared stimuli, and regular 
monitoring of symptoms has been effective in other populations.52 In the proposed study, the FREE program 
will incorporate CBT to reframe the fear experience and reduce the adverse emotional response. Exposure 
therapy will be used to reduce anxiety through habituation to previously anxiety-provoking situations.53 
Feedback using RT-CGM readings and review of a fear diary will be used as cues to reinforce learning. The 
goal is not to replace standard diabetes therapy, but improve diabetes self-management through fear 
reduction. Our premise is that negative thoughts, feelings, or experiences of hypoglycemia increase FOH. This 
compromises diabetes self-management and increases GV. Our program is designed to reduce FOH and 
improve diabetes self-management, which will lead to improved glycemic control and variability. (Figure 1).  

 
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Figure 1. Components of FREE program 
 
2. Innovation  
With most diabetes self-management research focused on blood glucose management,38-40 a FOH 
reduction intervention represents a novel approach to addressing the role of hypoglycemic fear in glycemic 
control and variability. Most individuals with T1DM struggle with hypo- and hyperglycemia and develop a 
profound fear from these experiences. FOH does not resolve with education alone,4 and the magnitude of the 
problem is poorly understood, as well as greatly under-appreciated. As the incidence of T1DM increases 
worldwide,54 the scope of the problem will only rise. To our knowledge, we are the first to identify the temporal 
relationships between FOH and GV (see 3.1b). These findings provide strong justification for an intervention 
that specifically targets FOH. In this R21, our team proposes to pilot test a CBT and exposure-based therapy 
intervention that is unique to diabetes care but has been effective in reducing fear and anxiety in other 
populations with chronic illness. This methodology will provide feedback on progress toward FOH reduction 
and GV through weekly diary and RT-CGM analysis. We focus on young adults because they have reported 
higher FOH levels than older adults and young children and they are becoming responsible for their diabetes 
management in new and challenging roles and situations. Improvement in diabetes self-management in this 
age group could facilitate the prevention or delay of diabetes complications later in life.  
 
3. Approach 
3.1. Preliminary Studies 
3.1a. Research Team Expertise. This application brings together an interdisciplinary team with shared 
(T1DM, FOH, CGM technology for GV measurement, chronic illness, clinical practice) and complementary 
(CBT, feedback, intervention studies, clinical diabetes education [CDE]) expertise. Collectively, the team’s 
research strengths span conceptual, methodological, clinical, statistical, and research abilities in the areas of 
self-management and chronic disease.  
3.1b. Preliminary Findings. We successfully conducted a study using a prospective repeated measures 
design, using CGM and a daily fear diary in 30 young adults with T1DM. FOH was linked to GV. (1) Significant 
temporal relationships emerged in which same-day fear levels were associated with same-day GV (r = .232, p 
= < .05), and previous-day fear levels were associated with next-day GV (r = .205, p < .05). This between-day 
relationship was stronger for those who experienced four or more hypoglycemic episodes per week (r = .483, p 
< .01). (2) FOH was reported by 78% of the sample. (3) During the 6-day CGM recording period, 27% were 
identified as hyper-responders, indicating that they reported and treated more presumed hypoglycemic 
episodes (based on daily diary entries) than actual biochemical hypoglycemic episodes measured through 
CGM recordings. (4) Optimal glycemic control (A1C < 7%) was not consistently associated with low GV. Our 
data demonstrated that nearly half (45%) of the sample had A1C levels at or below 7.0, yet 57% of those with 
optimal A1C levels had high GV (> 52 dl glucose standard deviation).  
3.2. Design and Methods 

 
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3.2a. Overview. Following a 1-week run-in phase, ten young adults aged 18 to 30 years with T1DM (≥ 1 
year) and who experience FOH will be randomized to an intervention or attention control group.  The 
intervention group will participate in eight weekly one-hour sessions using a CBT-based approach (FREE), 
wear a RT-CGM device, and keep a daily diary. The attention control group will also wear a RT-CGM device 
for 8 weeks but will not participate in weekly sessions and will not keep a diary. Data will be collected: (1) at the 
beginning of a 1-week run-in period (week 0); (2) at completion of the intervention at the end of 8 weeks (week 
8); and (3) post-program at 12 weeks. At completion, FOH, self-management, and A1C will be measured and 
RT-CGM recordings will be analyzed to determine within-group and between-group differences.  
3.2b. Setting and Sample. The study intervention will take place at the University of Illinois at Chicago 
(UIC) Medical Center and College of Nursing. Inclusion criteria: (1) 18-30 years old, (2) diagnosed with T1DM 
≥ 1 year and receive medical care from an endocrinologist, (3) use insulin pump therapy, and (4) have self-
reported FOH (screening questionnaire).55 Exclusionary criteria: (1) pregnant or breastfeeding, (2) actively 
treated for a mental health condition, (3) have a co-existing chronic illness or taking medications (excluding 
insulin) that may influence diabetes self-management or GV.  
3.2c. Recruitment. Subjects will be recruited through Chicago metropolitan area university medical 
centers, local diabetes websites, and organizations using flyers, e-announcements, and recruitment letters. At 
UIC, we will identify potentially eligible subjects through the electronic medical record system and send 
recruitment letters. The University of Illinois clinics saw over 900 patients with T1DM; thus, there is a sufficient 
pool from which to recruit. We have been successful in recruiting using these methods for our previous studies.  
3.2d. Sample Size Determination. The sample size of 10 subjects (n = 5 intervention group; 5 intention 
control group) will be sufficient to test the feasibility of the study protocol and to obtain preliminary outcome 
measures. 
3.2e. Procedures. Study staff will screen subjects for inclusion/exclusion criteria. Scores of 3 or 4, 
indicating that worry occurs often or very often, on any item on the worry scale (4-point Likert) of the 
Hypoglycemia Fear Scale (HFS-2)55 will be used to determine the presence of FOH (personal communication 
L. Gonder-Frederick, 5/26/15). Those who meet the study criteria will be scheduled for an appointment at the 
College of Nursing for the start of the 1-week run-in period to: obtain consent and baseline measures (Table 1, 
Week 0) and apply a RT-CGM device with instructions provided on its care. Following the 1-week run-in 
period, subjects will be randomized to the FREE intervention or attention control group. During the study 
period, subjects will continue to receive their usual diabetes care with their health care provider. The subjects 
will be encouraged to discuss any questions regarding blood glucose management with their diabetes health 
care provider.  
3.2e1. FREE Intervention. Subjects randomized to the FREE intervention group will: (1) attend eight 
weekly one-hour sessions based on principles of CBT and exposure treatment for specific phobias. The 
program will consist of 8 weeks of individual sessions (weeks 1-8), in which participants will be taught cognitive 
restructuring and exposure-based techniques to decrease their FOH. Treatment will target incorrect beliefs 
about hypoglycemia, hypervigilance to symptoms, fear of symptoms, and maladaptive behavioral responses in 
response to glucose levels. Participants will create a fear and avoidance hierarchy and be taught to begin 
approaching previously feared situations (e.g., spending time alone, reducing snacking, allowing glucose 
readings to reach lower safe levels, etc.) to experience habituation and the resulting decrease in anxiety. To 
maintain treatment fidelity, sessions will follow a manualized protocol (See Appendix A. Outline of FREE 
Intervention). Additionally, sessions will be audiotaped and reviewed for fidelity to the treatment protocol. 
Weekly homework will be assigned to reinforce the program content. (2) FREE intervention subjects will 
continue to wear a RT-CGM for the 8-week period and complete a daily FOH diary. RT-CGM recordings and 
daily diaries will serve as cues for glucose and fear levels. At each weekly visit, participants will receive a copy 
of their RT-CGM recordings for the previous week and (3) have their RT-CGM site changed by a study staff 
member who is a registered nurse.  
3.2e2. Attention Control Group. Subjects randomized to the attention control group will have (1) an initial 
meeting with study staff (study week 1) to review study purpose and goals,  (2) continue to wear a RT-CGM for 
the 8-week session; and (3) return to have their RT-CGM site changed weekly by study staff (registered 
nurse). The weekly visits for RT-CGM site changes will facilitate keeping the attention control group engaged 

 
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and will assure proper replacement of the glucose sensor (Appendix D). 
3.2e3. Subject Retention Strategy. Both the FREE intervention group and the attention control group will 
(1)  wear a RT-CGM; (3) receive reminders of their next appointment; and (4) have weekly visits to change the 
RT-CGM site. The weekly appointment reminders and RT-CGM site changes will be used to facilitate subject 
retention. Those in the FREE group will (5) receive additional intervention sessions week 1-8 and (6) weekly 
CGM downloads with GV analysis when they attend each session. (7) All subjects will be compensated for 
their time.  
3.2f. Measures. 
3.2f1. Baseline and Post-Intervention Measures. Self-report instruments will be used to obtain 
demographic and health information, previous history of hypoglycemia, fear of hypoglycemia, self-management 
behaviors, and related variables (self-efficacy, anxiety, diabetes distress). The scales have strong 
psychometric properties and have been validated in T1DM populations (Table 1). Glycemic control will be 
measured with a fingerstick for A1C for assessment of longer-term glycemic control using A1C Now® (Chek 
Diagnostics, Indianapolis, IA).  
3.2f2. Ongoing Measures: Diary. A daily diary will be used to measure daily fear levels and perceptions of 
GV for FREE participants only.  
Table 1. Measures  
 
 
Variables 
Measure 
Frequency 
Aim 1 Feasibility 
 
 
Recruitment 
Retention 
Acceptability 
Number of eligible respondents/Number consented 
Attendance rate; Completion rate 
Participant evaluation (Appendix C) 
Ongoing 
Weekly 
Week 8 
 
Aim 2 Program outcomes 
 
 
Previous hypoglycemia  
Hypoglycemia Patient Questionnaire2 
Week 0 
FOH  
Hypoglycemia Fear Scale (HFS-255) 
FREE group only: Daily FOH Diary: Fear level57  
(Appendix B) 
Week 0, Week 8, 12 
Daily 
Glycemic measures 
    Glycemic control  
    Glycemic variability 
 
 
 
 
Perception of glycemic variability 
 
A1C (A1C Now®)  
RT-CGM (Dexcom®): Daily glucose standard deviation 
(GlucSD), continuous net glycemic action (CONGA), 
coefficient of variation (CV%), interquartile range (IQR) 
and mean amplitude of glycemic excursions (MAGE) 
(see 3.2f3) 
FREE group only: Daily FOH diary: GV perception57 
(Appendix B) 
 
Week 0, Week 8, 12 
Daily 
 
 
 
 
Daily 
Diabetes self-management 
Diabetes Self-Management Questionnaire58 
 
Week 0, Week 8, 12 
 
Other psychological covariates to 
characterize sample: self-efficacy, 
anxiety; mood, diabetes distress 
Self-Efficacy for Diabetes59 
PROMIS Anxiety and Depressive Mood Scales 
Diabetes Distress61 
Week 0, Week 8, 12 
Week 0, Week 8, 12 
Week 0, Week 8, 12 
 
3.2f3.Ongoing Measures: Glycemic Variability. Subcutaneous interstitial glucose levels will be 
monitored during the run-in phase (over a period of 7 days) and the 8-week intervention (FREE intervention 
and attention control groups) using a Dexcom G4 Platinum® (San Diego, CA). A glucose sensor and recorder 
will be placed on the abdomen and changed weekly by a trained study staff member (a registered nurse). All 
subjects will be able to view their RT-CGM values. At the end of each week, all data will be downloaded to the 
Dexcom Software and examined for glycemic trends and excursions. The weekly glucose summary will be 
provided to subjects in the intervention group at each weekly session to provide feedback on their glucose 
trends. Those in the attention control group will be able to view their CGM readings in real-time but will not 
receive weekly summaries. Rather, at the end of the full study (i.e., 12 weeks), they will receive their weekly 

 
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summaries. 
To analyze GV for study outcomes, the raw data will be downloaded to an EXCEL spreadsheet. The 
research staff will be trained on data cleaning, confirmation of regular calibration, identification of errors, and 
review of missing data or time-points. The amount of time spent in hypo- and hyperglycemia will be calculated 
(% and minutes; < 70 and > 180 mg/dl). GV will be determined by calculating the daily glucose standard 
deviation (GlucSD), continuous net glycemic action (CONGA), coefficient of variation (CV%), interquartile 
range (IQR), and mean amplitude of glycemic excursions (MAGE). These are measures that are 
recommended to obtain a comprehensive evaluation of GV.62,63  
3.2g. Data Analysis 
1. The feasibility of the program will be evaluated by assessment of recruitment, retention, and participant 
evaluation. Itemized logs of recruitment sites, methods, responses, eligible subjects, and consented subjects 
will be documented. Retention will be evaluated through documentation of weekly attendance and compliance 
with RT-CGM site changes. As part of the feasibility assessment, we will also track the number of RT-CGM 
sensor failures, RT-CGM placement sites, time to failure, and any adverse sensor site problems. Acceptability 
will be determined through participant evaluation (Appendix C).  
2.) We will calculate means and standard deviations of within-group and between-group differences from 
baseline to program completion (8th week) and post-program (12th week) on the outcomes of FOH, self-
management, glycemic control (A1C), and GV.   
 
3.2h. Timeline 
Year 1 
Mar 
Apr 
May 
June 
July 
Aug 
Sept 
Oct 
Nov 
Dec 
Jan 
Feb 
Mar 
Total 
Study set up 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
FREE subjects 
 
 
 
2 
 
2 
 
 
1 
 
 
 
 
5 
Control subjects 
 
 
 
2 
 
2 
 
 
1 
 
 
 
 
5 
Total subjects 
 
 
 
4 
 
4 
 
 
2 
 
 
 
 
10 
 
3.2j. Pilot study limitations. One of the limitations is that the small convenience sample may not be 
representative of the population. This limitation is offset by the fact that this is strictly a feasibility pilot to inform 
and strengthen a larger study in terms of recruitment, retention and acceptability.  
 
 

 
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