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      Fear of hypoglycemia—An underestimated problem

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          Abstract

          Introduction

          Fear of hypoglycemia (FOH) is a phenomenon that affects people with diabetes experiencing hypoglycemia. On the one hand, FOH is an adaptive mechanism that helps to protect patients from hypoglycemia and its consequences. On the other hand, the non‐normative level of FOH causes anxiety and tension, disturbs normal functioning, and makes normoglycemia maintenance difficult.

          Objective

          The main objective of this review was to describe factors influencing FOH and methods of measurement of FOH levels. Moreover, we highlighted the impact of the new technologies used in diabetes therapy on FOH and different therapeutic possibilities helping patients cope with excessive levels of FOH. We also presented clinical cases of patients with high FOH levels met in clinical practice and discussed methods to better diagnose and assist people with this kind of problem.

          Methods

          We searched for studies and articles via PubMed using the keywords fear of hypoglycemia, diabetes, and hypoglycemia. From screened documents identified from literature search, 67 articles were included in our review.

          Results

          We divided results from literature screening into five parts: fear of hypoglycemia and hypoglycemia definition, risk factors for the FOH, methods of measuring levels of FOH, therapies for the FOH, and modern technologies. We also described clinical examples of abnormal fear of hypoglycemia in patients.

          Conclusion

          The review highlights the importance of taking into consideration fear of hypoglycemia phenomenon in diabetic patients in everyday clinical practice.

          Abstract

          Fear of hypoglycemia is a phenomenon that affects people with diabetes experiencing hypoglycemia. On the one hand, fear of hypoglycemia is an adaptive mechanism that helps to protect patients from hypoglycemia and its consequences. On the other hand, the non‐normative level of fear of hypoglycemia causes anxiety and tension, disturbs normal functioning, and makes normoglycemia maintenance difficult.

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          Most cited references67

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          The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus

          S Genuth, C. Siebert, D. M. Nathan … (1993)
          Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications. A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia. Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
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            Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes

            Laurent Billot (2008)
            In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain. We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately. After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001). A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.) 2008 Massachusetts Medical Society
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              Glucose control and vascular complications in veterans with type 2 diabetes.

              William Duckworth, Carlos Abraira, Thomas Moritz … (2009)
              The effects of intensive glucose control on cardiovascular events in patients with long-standing type 2 diabetes mellitus remain uncertain. We randomly assigned 1791 military veterans (mean age, 60.4 years) who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. Other cardiovascular risk factors were treated uniformly. The mean number of years since the diagnosis of diabetes was 11.5, and 40% of the patients had already had a cardiovascular event. The goal in the intensive-therapy group was an absolute reduction of 1.5 percentage points in the glycated hemoglobin level, as compared with the standard-therapy group. The primary outcome was the time from randomization to the first occurrence of a major cardiovascular event, a composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease, and amputation for ischemic gangrene. The median follow-up was 5.6 years. Median glycated hemoglobin levels were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (hazard ratio in the intensive-therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P=0.14). There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81 to 1.42; P=0.62). No differences between the two groups were observed for microvascular complications. The rates of adverse events, predominantly hypoglycemia, were 17.6% in the standard-therapy group and 24.1% in the intensive-therapy group. Intensive glucose control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events, death, or microvascular complications with the exception of progression of albuminuria (P = 0.01) [added]. (ClinicalTrials.gov number, NCT00032487.) 2009 Massachusetts Medical Society
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                Author and article information

                Contributors
                Agnieszka Przezak:
                ORCID: https://orcid.org/0000-0003-1164-3960
                agn-prze@wp.pl
                Journal
                Journal ID (nlm-ta): Brain Behav
                Journal ID (iso-abbrev): Brain Behav
                Journal ID (doi): 10.1002/(ISSN)2157-9032
                Journal ID (publisher-id): BRB3
                Title: Brain and Behavior
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2162-3279
                Publication date (Electronic): 27 May 2022
                Publication date Collection: July 2022
                Volume: 12
                Issue: 7 ( doiID: 10.1002/brb3.v12.7 )
                Electronic Location Identifier: e2633
                Affiliations
                [ 1 ] Department of Diabetology and Internal Medicine Pomeranian Medical University Szczecin Poland
                Author notes
                [*] [* ] Correspondence

                Agnieszka Przezak, Department of Diabetology and Internal Medicine, Pomeranian Medical University in Szczecin, Siedlecka 2, 72‐010 Police, Szczecin, Poland.

                Email: agn-prze@ 123456wp.pl

                Author information
                https://orcid.org/0000-0003-1164-3960
                Article
                Publisher ID: BRB32633
                DOI: 10.1002/brb3.2633
                PMC ID: 9304823
                PubMed ID: 35620854
                SO-VID: fc194828-4f01-40a1-ba25-b710c60c4275
                Copyright © © 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date revision received : 22 March 2022
                Date received : 15 December 2021
                Date accepted : 26 March 2022
                Page count
                Figures: 3, Tables: 1, Pages: 9, Words: 7199
                Categories
                Subject: Review
                Subject: Review
                Custom metadata
                source-schema-version-number 2.0
                cover-date July 2022
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:22.07.2022

                ScienceOpen disciplines: Neurosciences
                Keywords: anxiety,diabetes,fear of hypoglycemia,hypoglycemia
                Data availability:
                ScienceOpen disciplines: Neurosciences
                Keywords: anxiety, diabetes, fear of hypoglycemia, hypoglycemia

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