Fear of hypoglycemia in adults with type 1 diabetes: impact of therapeutic advances and strategies for prevention - a review

doi:10.1016/j.jdiacomp.2015.09.003

Journal of Diabetes and its Complications

Volume 30, Issue 1, January–February 2016, Pages 167-177

https://doi.org/10.1016/j.jdiacomp.2015.09.003 Get rights and content

Abstract

Purpose

This review summarizes the current state of the science related to fear of hypoglycemia (FOH) in adults with type 1 diabetes. Fear of hypoglycemia is a critical deterrent to diabetes self-management, psychological well-being, and quality of life. We examine the influence of contemporary treatment regimens, technology, and interventions to identify gaps in knowledge and opportunities for research and practice.

Basic Procedures

A literature search was conducted of MEDLINE, PsycINFO, and EMBASE. Fifty-three studies that examined fear of hypoglycemia were included.

Main Findings

Fear of hypoglycemia influences diabetes management and quality of life. Gender and age differences exist in experiences and responses. Responses vary from increased vigilance to potentially immobilizing distress. Fear of hypoglycemia is greater at night and may contribute to poor sleep quality. Strategies to reduce fear of hypoglycemia have had varying success. Newer technologies hold promise but require further examination.

Conclusions

Fear of hypoglycemia remains a problem, despite advances in technology, insulin analogs, and evidence-based diabetes management. Clinical care should consistently include assessment for its influence on diabetes self-management and psychological health. Further research is needed regarding the influence of newer technologies and individualized strategies to reduce fear of hypoglycemia while maintaining optimal glucose control.

Introduction

Hypoglycemia remains the major limiting factor in achieving optimal blood glucose control in persons with type 1 diabetes (T1DM) (Cryer, 2002). Hypoglycemia (blood glucose level < 70 mg/dl) (Seaquist et al., 2013) can be inconvenient, associated with psychological distress, and, if severe (requiring third-party assistance), linked with increased morbidity and mortality (Anarte Ortiz et al., 2011, Anderbro et al., 2010).

The Diabetes Control and Complications Trial (DCCT) demonstrated significant reduction in microvascular complications with intensive insulin therapy that achieved lower glycosylated hemoglobin levels compared to conventional insulin therapy (Diabetes Control and Complications Trial Research Group, 1993). Still, many adult patients using intensive therapy do not achieve optimal glucose levels. Population data from the Type 1 Diabetes Exchange clinic registry reported that only 14% of those aged 18–25 years and 29% aged 26–50 years achieved an A1C less than 7% (Miller et al., 2015). The gap in achieving evidence-based recommendations in practice may in part be related to barriers in the daily self-management of the disease and particularly the risk that hypoglycemia increases as blood glucose levels approach normal levels (Cryer, 2002). Despite a reduction in severe hypoglycemia (SH; requiring third-party assistance) with lower A1C levels (Barnard et al., 2012, Barnard and Skinner, 2008), iatrogenic hypoglycemia remains a major barrier to optimal glucose control (Cryer, 2014). Hypoglycemia avoidance strategies may conflict with achieving optimal glucose control (Irvine, Cox, & Gonder-Frederick, 1992).

Despite refinements in insulin therapy and advancements in glucose-sensing technology over the past few decades, fear of hypoglycemia (FOH) remains a critical deterrent to diabetes self-management, psychological well-being, and quality of life (QOL) among those with T1DM (Bohme, Bertin, Cosson, & Chevalier, 2013). The purpose of this review is to (1) summarize the current state of the science related to FOH in adults with T1DM, taking into account modern treatment regimens and technology, (2) summarize results of interventions to reduce FOH, (3) identify gaps in knowledge, and (4) provide recommendations for research and practice. The focus of this review was on adults with T1DM who have transitioned or are in the process of transitioning to independent diabetes care. Studies of children were excluded because FOH and the emotional and behavioral responses to fear/worry may be influenced by parents/caregivers and may not reflect their own thoughts and behaviors.

Section snippets

Review methods

MEDLINE, PsycINFO, and EMBASE were systematically searched using the subject headings and keywords: type 1 diabetes and fear of hypoglycemia, or worry, or hypoglycemia, or adherence, or quality of life. No publication date restrictions were used. Inclusion criteria were: English language articles reporting primary research findings in adults with T1DM in which fear/worry or anxiety related to hypoglycemia was studied or measured. Reference lists were also reviewed for sources. The search

Definition of fear of hypoglycemia

Fear has been conceptualized as an emotion associated with an immediate and specific threat or danger (Davis, Walker, Miles, & Grillon, 2010) that operates as an intervening variable between context-specific stimuli (fear triggers) and responses (e.g., fear behaviors) (Adolphs, 2013). Fear is related to anxiety; however, anxiety is evoked by less explicit or foreseeable threats that are farther into the future (Davis et al., 2010). At the extreme, fears can develop into anxiety disorders and

Measurement of FOH

FOH has predominantly been measured using the 27-item Hypoglycemia Fear Scale (HFS; (Cox, Irvine, Gonder-Frederick, Nowacek, & Butterfield, 1987) and 23-item HFS-I (Irvine, Cox, & Gonder-Frederick, 1994), later revised to HFS-II) (Gonder-Frederick et al., 2011). Scale items were originally based on interviews with diabetes health care providers and patients with T1DM and further refined several years later using a similar process with a factor analysis and Rasch analysis for the revised scale.

Gender and other demographic influences

Women tended to experience higher FOH levels than men (Desjardins et al., 2014, Diabetes Control and Complications Trial Research Group, 1993, Belendez and Hernandez-Mijares, 2009, Cappuccio et al., 2011, Cox et al., 2001, Cox et al., 2008). Frequency of severe hypoglycemic (SH) episodes (requiring third-party assistance) and the number of symptoms occurring with mild hypoglycemia (a subjective feeling that one's glucose was low) were associated with fear for both genders (Anderbro et al., 2010

History of previous hypoglycemic episodes and hypoglycemic unawareness

FOH is triggered by both the frequency and severity of hypoglycemic symptoms. (Desjardins et al., 2014, Diabetes Control and Complications Trial Research Group, 1993, Gjerlow et al., 2014, Gold et al., 1997, Goebel-Fabbri et al., 2008) There has been consistent evidence that worry is significantly associated with SH episodes experienced within the previous 12 months (Desjardins et al., 2014, George et al., 2008, Belendez and Hernandez-Mijares, 2009, Gold et al., 1997, Gonder-Frederick et al.,

Time of day, disruption of sleep

FOH, as well as actual episodes of hypoglycemia, tends to be greater at night (George et al., 2008, Cappuccio et al., 2011). Following a nocturnal hypoglycemic episode, individuals reported poor sleep quality, with 13.4% unable to fall back asleep and only 32.4% feeling they had a good night's sleep (Brod, Christensen, & Bushnell, 2012). Martyn-Nemeth et al. reported that poor sleep quality was associated with FOH (Martyn-Nemeth, Quinn, Phillips, & Mihailescu, 2014a). FOH may lead to increased

Psychosocial factors

Other important factors affecting FOH are the individual's emotional state and coping ability (Hanna et al., 2013, Bazzazian and Besharat, 2012). Anxiety, stress, anger, depression, and impaired QOL have been associated with FOH (George et al., 2008, Gjerlow et al., 2014, Bazzazian and Besharat, 2012), further complicating the problem. Anxiety may mimic the symptoms of hypoglycemia and impair its detection (Hermanides et al., 2011, Hendrieckx et al., 2014). Also, being anxious or stressed may

Diabetes self-management

FOH influences health behaviors used in diabetes self-management, including insulin dosing, dietary patterns, and physical activity (Belendez and Hernandez-Mijares, 2009, Ismail et al., 2008, Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group et al., 2010, Karges et al., 2014, Jacobson et al., 2007, Kilgus et al., 2009, Knutson and Van Cauter, 2008). Adhering to tight glucose control can increase fear. Dietary modifications may include excessive eating, particularly

Glycemic control and variability

Longer-term glycemic control is generally measured by hemoglobin A1C. The association between A1C and FOH has been inconsistent among studies (George et al., 2008, Belendez and Hernandez-Mijares, 2009, Cox et al., 2008, Linkeschova et al., 2002, Fulcher et al., 2014, Bazzazian and Besharat, 2012, Little et al., 2014). FOH (behavior) scores have been higher for those with less-optimal A1C levels in some studies, supporting the notion that greater FOH induced patients to maintain higher blood

Technology and fear of hypoglycemia

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 pens, insulin pumps, insulin bolus calculators, and diabetes-related mobile applications. While the intent of these devices is to improve glucose control, they can impact psychological variables, such as FOH. Current research on the relationship between technological devices and FOH is

Interventions and their effectiveness

A crucial question is whether interventional programs can minimize FOH. Programs with either a primary or secondary target to reduce FOH included: diabetes education, cognitive behavioral therapy (CBT), blood glucose awareness training (BGAT), motivational enhancement therapy, improvement in hypoglycemic unawareness (e.g., HypoCOMPaSS), and telemedicine interventions (Schachinger et al., 2005, Hermanides et al., 2011, Schmidt and Norgaard, 2012, Seaquist et al., 2013, Snoek et al., 2001,

Implications for practice and research

Despite advances in technology, insulin analogs, and evidence-based diabetes management, FOH remains a problem. Reduced biochemical hypoglycemia is not consistently associated with reduced FOH. From a clinical perspective, assessment of FOH should be part of the routine plan of care to assess its influence on diabetes management, psychological well-being, and social and employment relationships.

Major gaps in knowledge still exist with regard to racial, ethnic, socioeconomic, age, diabetes

Acknowledgements

The authors would like to thank Kevin Grandfield, Publication Manager of the UIC Department of Biobehavioral Health Science, for editorial assistance.

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Automated insulin delivery systems improve blood glucose control in patients with type 1 diabetes (T1D). However, optimizing their performance requires patient's proper compliance to meal insulin bolus administration. We explored real-life prevalence of delayed prandial boluses (DBs) in adults with T1D on advanced technologies, and their association with glycemic control and fear of hypoglycemia (FH).
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Mean DBs over two weeks were 10.2 ± 4.7 (M ± SD, range 1–23) and more frequent in women than men (11.0 ± 4.6 vs. 9.4 ± 4.7, p = 0.036). Participants with more DBs (>12) showed significantly lower Time-In-Range (62.4 ± 13.8 vs. 76.6 ± 9.0 %) than those with less DBs (<7.7), along with higher Time-Above-Range, GMI, and Coefficient-of-Variation (ANOVA, p < 0.001 for all). Participants with higher FH score showed more DBs (11.6 ± 5.0) than those in lower tertiles (9.57 ± 4.59 and 9.47 ± 4.45, ANOVA p = 0.045).
In patients on advanced technologies, delayed boluses are extremely common, and associate with significantly worse glycemic control. Utmost attention is needed to bolus timing, mainly tackling fear of hypoglycemia.
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To investigate whether the FreeStyle Libre, an intermittent scanning continuous glucose monitoring (isCGM) system, influences confidence in managing hypoglycemia in adults with type 1 diabetes.
This longitudinal, observational study conducted at one facility included 121 adults with type 1 diabetes. Participants used the conventional finger-prick method for self-testing glucose before using isCGM. At baseline and 12 months after initiating isCGM, the Hypoglycemic Confidence Scale (HCS), Diabetes Treatment Satisfaction Questionnaire (DTSQ), and HbA1c were performed. At 12 months, the percentage of individuals utilizing isCGM trend arrows for glucose management was observed. The primary endpoint was hypoglycemic confidence change attributed to using isCGM.
After using isCGM, HCS scores improved significantly from 2.89 (2.56, 3.22) to 3.00 (2.20, 3.33) (p < 0.001); median (25%, 75%). Among participants with level 3 hypoglycemia at baseline, hypoglycemic confidence during sleep (p < 0.05), in social situations (p < 0.05), and in avoiding serious hypoglycemia-related problems (p < 0.05) were improved. Despite hypoglycemia risk, participants could continue daily activities by using isCGM (p < 0.05), and sixty-nine percent utilized trend arrows effectively.
Using isCGM improved hypoglycemic confidence among adults with type 1 diabetes. Data analysis indicated that people with type 1 diabetes could live more freely and better manage hypoglycemia using isCGM.
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Fear of hypoglycaemia (FOH) significantly disrupts the daily management of type 1 diabetes (T1D) and increases the risk of complications. Recent technological advances can improve glucose metrics and reduce hypoglycaemia frequency, yet their impact on FOH is unclear. This systematic review and meta-analysis (SRMA) aimed to synthesize the current literature to understand the impact of diabetes technologies on FOH in T1D.
In this SRMA, we searched PubMed, Medline, Scopus, and Web of Science from inception up to May 21st, 2023 for studies assessing the effect of using real-time or intermittently scanned continuous glucose monitors (rtCGM or isCGM); insulin pumps (CSII); and their combinations on FOH as the primary outcome, measured using the Hypoglycaemia Fear Survey (HFS; including total, worries [HFS-W], and behaviours [HFS-B] scores), in non-pregnant adults with T1D. Data was extracted by the first and second authors. Results were pooled using a random-effects model based on study design (RCT and non-RCT), with subgroup analysis based on the type of technology, reported change in hypoglycaemia frequency, and duration of use. Risk of bias was evaluated with Cochrane and Joanna Briggs Institute tools. This study is registered with PROSPERO, CRD42021253618.
A total of 51 studies (n = 8966) were included, 22 of which were RCTs. Studies on rtCGM and CSII reported lower FOH levels with ≥8 weeks of use. Studies on CSII and rtCGM combinations reported lower FOH levels after ≥13 weeks of automated insulin delivery (AID) use or 26 weeks of sensor-augmented pump (SAP) use. The meta-analysis showed an overall lower FOH with technologies, specifically for the HFS-W subscale. The RCT meta-analysis showed lower HFS-W scores with rtCGM use (standard mean difference [95%CI]: −0.14 [−0.23, −0.05], I² = 0%) and AID (−0.17 [−0.33, −0.01], I² = 0%). Results from non-RCT studies show that SAP users (−0.33 [−0.38, −0.27], I² = 0%) and rtCGM users (−0.38 [−0.61, −0.14], I² = 0%) had lower HFS-W.
We found consistent, yet small to moderate, effects supporting that diabetes technologies (specifically rtCGM, SAP, and AID) may reduce hypoglycaemia-related worries in adults with T1D. Current literature, however, has limitations including discrepancies in baseline characteristics and limited, mainly descriptive, statistical analysis. Thus, future studies should assess FOH as a primary outcome, use validated surveys, and appropriate statistical analysis to evaluate the clinical impacts of technology use beyond just glucose metrics.
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The chapter presents a third-wave CBT intervention for coping with fear of hypoglycemia (FOH). The method was developed at the Pediatric Endocrinology Clinic at Sheba Academic Medical Hospital among adolescents with type 1 diabetes (T1DM). Through a case study of a 16-year-old female patient after several events of severe hypoglycemia, we introduce the stages of an 18-session therapeutic process. The chapter demonstrates the techniques employed during the sessions for decreasing the patient’s posttraumatic stress symptoms. The process aimed to help the patient regulate her emotions, understand the essence of her thoughts as mental events and not as objective reality, expand her focus of attention, identify her values, and employ mindfulness tension relieving exercises.

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Fear of hypoglycemia in adults with type 1 diabetes: impact of therapeutic advances and strategies for prevention - a review

Abstract

Purpose

Basic Procedures

Main Findings

Conclusions

Introduction

Section snippets

Review methods

Definition of fear of hypoglycemia

Measurement of FOH

Gender and other demographic influences

History of previous hypoglycemic episodes and hypoglycemic unawareness

Time of day, disruption of sleep

Psychosocial factors

Diabetes self-management

Glycemic control and variability

Technology and fear of hypoglycemia

Interventions and their effectiveness

Implications for practice and research

Acknowledgements

Current Biology

Patient Education and Counseling

Patient Education and Counseling

Diabetes & Metabolism

Behaviour Research and Therapy

Primary Care Diabetes

Diabetes Research and Clinical Practice

Endocrine Practice

Patient Education and Counseling

Development of a new fear of hypoglycemia scale: FH-15

Psychological Assessment

Fear of hypoglycaemia in adults with Type 1 diabetes

Diabetic Medicine

Fear of hypoglycemia: relationship to hypoglycemic risk and psychological factors

Acta Diabetologica

Use of an automated bolus calculator reduces fear of hypoglycemia and improves confidence in dosage accuracy in patients with type 1 diabetes mellitus treated with multiple daily insulin injections

Journal of Diabetes Science and Technology

Cross-sectional study into quality of life issues surrounding insulin pump use in type 1 diabetes

Practical Diabetes International

Closing the loop overnight at home setting: psychosocial impact for adolescents with type 1 diabetes and their parents

BMJ Open Diabetes Research Care

An explanatory model of adjustment to type I diabetes based on attachment, coping, and self-regulation theories

Psychology, Health & Medicine

Beliefs about insulin as a predictor of fear of hypoglycaemia

Chronic Illness

Further development of a quality-of-life measure for IDDM patients [Abstract]

Diabetologia

Validation of a diabetes-specific quality-of-life scale for patients with type 1 diabetes

Diabetes Care

Barriers to physical activity among patients with type 1 diabetes

Diabetes Care

Impact of nocturnal hypoglycemic events on diabetes management, sleep quality, and next-day function: results from a four-country survey

Journal of Medical Economics

Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies

European Heart Journal

Fear of hypoglycemia in type 1 (insulin-dependent) diabetic patients

Romanian Journal of Internal Medicine

Psychobehavioral metabolic parameters of severe hypoglycemic episodes

Diabetes Care

Blood glucose awareness training (BGAT-2): long-term benefits

Diabetes Care

Fear of hypoglycemia: quantification, validation, and utilization

Diabetes Care

Blood glucose awareness training delivered over the internet

Diabetes Care

Hypoglycaemia: the limiting factor in the glycaemic management of Type I and Type II diabetes

Diabetologia

Glycemic goals in diabetes: trade-off between glycemic control and iatrogenic hypoglycemia

Diabetes

Multivariate models of health-related utility and the fear of hypoglycaemia in people with diabetes

Current Medical Research and Opinion

Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety

Neuropsychopharmacology

Are bedtime nutritional strategies effective in preventing nocturnal hypoglycaemia in patients with type 1 diabetes?

Diabetes, Obesity & Metabolism

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus

New England Journal of Medicine

Hypoglycemia associated autonomic failure. [Review]

Clinical Autonomic Research