Is hypoglycemia fear independently associated with health-related quality of life?
© Shi et al.; licensee BioMed Central Ltd. 2014
Received: 5 May 2014
Accepted: 6 November 2014
Published: 30 November 2014
Patients may fear the symptoms and consequences associated with hypoglycemia. We tested whether fear of hypoglycemia is independently associated with poorer health-related quality of life (HRQOL).
Research design and methods
Data were collected using direct-mail survey and enrollment information from adult commercial health plan enrollees with type 2 diabetes during a 12-month period (12/01/2008 to 11/30/2009). HRQOL was evaluated by the EuroQol (EQ)–5D index and 12-item Short Form Health Survey Mental Component Summary (SF-12 MCS) and Physical Component Summary (SF-12 PCS). Fear of hypoglycemia was assessed using the Hypoglycemia Fear Survey (HFS). Two ordinary least-squares (OLS) models of HRQOL controlling for demographics and illness characteristics were specified, and OLS regression coefficients and statistical inferences were compared. Model 1 included 1 variable of hypoglycemia symptoms; Model 2 included both hypoglycemia symptoms and HFS score.
Of 3999 patients contacted, 813 responded to the survey. Model 1: hypoglycemia symptoms alone were associated with worse HRQOL (SF-12 MCS and SF-12 PCS scores and EQ-5D utility score; all P < 0.05). Model 2: hypoglycemia symptoms were significantly associated only with SF-12 MCS score. HFS total score was significantly associated with all 3 HRQOL scores. Hypoglycemia symptoms, Hispanic ethnicity, and longer diabetes duration were associated with greater hypoglycemia fear. Higher income, white race, and treatment without sulfonylurea or insulin were associated with less hypoglycemia fear (all P < 0.05).
In addition to the effect of symptomatic hypoglycemia on HRQOL, fear of hypoglycemia was independently associated with lower overall health status and mental and physical health.
Hypoglycemia is associated with increased risk of a variety of adverse clinical outcomes in patients with type 2 diabetes, including microvascular events (eg, nephropathy, retinopathy, neuropathy), macrovascular events (eg, heart failure, peripheral vascular disease, myocardial events, stroke), and death -. High rates of hypoglycemia symptoms (38%–63%) - and hypoglycemia episodes (14%–23%; based on low blood sugar) , are observed in patients with type 2 diabetes in general clinical practice. Hypoglycemia is primarily associated with treatment with insulin and insulin secretagogues . A nationwide cohort study demonstrated that patients who experience hypoglycemia are more likely to be using insulin and sulfonylureas than those who do not experience hypoglycemia. Hypoglycemia, use of insulin, and use of sulfonylureas are associated with increased risk for major cardiovascular (CV) events, CV disease, and death . Risk of hypoglycemia also increases with age and duration of diabetes .
Patients may fear the symptoms associated with a mild episode of hypoglycemia as well as the consequences of severe hypoglycemia, which may include seizure or loss of consciousness .
Fear of hypoglycemia is a considerable problem in patients with diabetes , and may itself represent a barrier to glycemic control. Hypoglycemia is associated with lower health-related quality of life (HRQOL) ,,,, depression , and lower treatment satisfaction ,, which could undermine treatment adherence . Fear of hypoglycemia may lead to preventive coping behaviors, such as taking less insulin or increasing food intake ,, that negatively affect glycemic control. Fear of hypoglycemia may also lead physicians to limit the aggressiveness of therapy .
In a cross-sectional survey study, we found that symptomatic hypoglycemia was associated with worse HRQOL as well as greater fear of hypoglycemia . Compared with patients who did not report a history of symptomatic hypoglycemia, patients with a confirmed history of symptomatic hypoglycemia had higher scores on the Hypoglycemia Fear Survey (HFS) Behavior and Worry subscales (indicating more fear of and worry about hypoglycemia; each P < 0.001), lower scores on the EuroQol (EQ)–5D index (indicating poorer health status, P < 0.001), and lower scores on the 12-item Short Form Health Survey (SF-12) Mental Component Summary (MCS) score (P < 0.001) and Physical Component Summary (PCS) score (P = 0.002). The objective of this retrospective analysis was to examine the relationships among symptomatic hypoglycemia, patient self-reported fear of hypoglycemia, and HRQOL while controlling for patient baseline demographic and disease characteristics. We tested the hypothesis that, beyond the effect of symptomatic hypoglycemia itself on patient HRQOL, fear of hypoglycemia is independently associated with lower HRQOL.
Research design and methods
Detailed methodology for this cross-sectional observational research study was previously published . The study combined patient-reported data collected through mail surveys and retrospective analysis of administrative claims data (medical data, pharmacy data, and enrollment information) from a large US health plan (the Life Sciences Research Database). The study protocol was approved by a central institutional review board (IRB) prior to study initiation. And due to the fact that the patients in our study were identified from administrative claims data, the study concept was also approved by the large US health plan prior to commencement of the study. Participants were adult enrollees in the health plan with a diagnosis of type 2 diabetes and ≥2 pharmacy claims for an oral antidiabetic medication (OAD) with or without insulin identified in the administrative claims data from December 1, 2008, to November 30, 2009.
For the survey, patients (N = 3999) were contacted directly by mail. The patient survey assessed demographic variables, age at time of type 2 diabetes diagnosis, family history of diabetes, and smoking status. Patients were asked about their current OAD, duration of treatment, and modifications to their treatment within the previous 6 months. Medication adherence was assessed using the Morisky self-report medication adherence 4-item questionnaire .
Fear of hypoglycemia was evaluated using the HFS . This validated assessment lists 15 behaviors that patients may engage in to avoid low blood sugar, with potential consequences, and 18 items related to low blood sugar about which patients with diabetes may be concerned. The recall period was 6 months. A total score, Behavior subscale score (sum of the 15 behavioral items), and Worry subscale score (sum of the 18 worry items) were generated. In addition, patients were asked whether they had changed their medication or were afraid to change medications because of hypoglycemia.
Health-related quality of life was assessed using 2 instruments. Overall health status was assessed using the EQ-5D, a standardized measure that rates 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) across 3 levels (no problems, some/moderate problems, and extreme problems) ,. The index value (ie, health utility) between 0 (death) and 1 (perfect health) was calculated using the value sets (weights) from a US population sample. The other instrument was the SF-12 , which can produce an MCS and a PCS. Summary scores range from 0 to 100, with a higher score indicating a better quality of life in mental and physical components. Hypoglycemia was defined based on American Diabetes Association symptoms  and blood glucose readings at the time that symptoms occurred.
The survey packet we used in this study contained a pre-paid cash incentive of $10 to the patients, along with the invitation letter printed on letterhead, the IRB-approved consent form, the survey instrument printed in booklet form, and a postage-paid business reply envelope. We sent reminders to the patients 2 and 4 weeks following the initial survey to increase our response rate.
Survey variables (eg, demographics and clinical characteristics) were analyzed descriptively, and bivariate comparisons of demographic characteristics and outcome measures were performed using appropriate tests (eg, t-test or chi-square test) based on the distribution of the measure. Multivariate analyses of HFS, SF-12, and EQ-5D outcomes were conducted using ordinary least squares. Specific predictors (ie, explanatory variables) to be included were selected primarily based on clinical rationale. Associations among symptomatic hypoglycemia, fear of hypoglycemia, and HRQOL were modeled in 2 ordinary least-squares regressions, controlling for sociodemographics, illness characteristics, and treatment factors . Model 1 of the HRQOL = f (symptomatic hypoglycemia) tested the associations between symptomatic hypoglycemia and HRQOL, and based on previously published results , these were expected to be statistically significant. Model 2, which was the primary assessment of the study hypothesis, added 1 additional variable of hypoglycemia fear and tested the impact that fear of hypoglycemia had on health status independently of the impact of hypoglycemia symptoms. Following standard procedure, regression diagnostics were performed to assess goodness of fit and violations of model assumptions (eg, multicollinearity, heteroskedasticity) for each model. Any violations of the model were noted and appropriate corrections made to the data. The fitted and observed data were examined to uncover outliers, their effect on the analysis, and possible misspecification of the initial equation. SAS 9.2 software (SAS Institute, Inc., Cary, NC) was used for statistical analyses . The significance level was set at 0.05 (2-tailed).
Because different classes of antidiabetic drugs may be more likely to cause hypoglycemia -, the association between fear for hypoglycemia and quality of life might also be different across different patient subgroups of antidiabetic medication users. Due to this concern, the same statistical analysis procedures were conducted on two patient subgroups of antidiabetic medication users: insulin users and sulfonylurea users.
Patient survey results
Population characteristics between patients who reported versus those who did not report symptoms of hypoglycemia
Characteristic, n (%)
No hypoglycemia(n = 235)
Hypoglycemia(n = 578)
Family history of diabetes
Any OAD with insulin
SU without insulin
Non-SU OAD without insulin
Diabetes treatment period, y
Black or African American
Hispanic or Latino
Single, never married
Annual household income, $US
Less than secondary
Secondary or equivalent
Tertiary but no degree
2-year undergraduate degree
>2-year undergraduate degree
Influencing factors of hypoglycemia fear survey total scores
Age (<65 y)
Body mass index
Family history of diabetes
Treatment (SU without insulin)
Non-SU OAD without insulin
Any OAD with insulin
Duration of current diabetes medication
White (not white)
Hispanic or Latino (not Hispanic or Latino)
Married (currently not married)
Household income level
Education (less than secondary)
Diabetes duration (y)
Role of hypoglycemia fear on health-related quality of life using alternative models
95%CI for β
95%CI for β
95%CI for β
−0.067 to −0.015
−5.259 to −1.998
−2.623 to 0.675
−0.040 to 0.013
−3.591 to −0.283
−1.104 to 2.262
−0.003 to −0.002
−0.210 to −0.115
−0.197 to −0.101
Role of hypoglycemia fear on health-related quality of life using alternative models (Insulin Subgroup)
95%CI for β
95%CI for β
95%CI for β
−0.058 to 0.055
−5.813 to 0.801
−5.244 to 1.908
−0.027 to 0.086
−3.534 to 2.965
−4.011 to 3.296
−0.004 to −0.001
−0.259 to −0.116
−0.191 to −0.031
Role of hypoglycemia fear on health-related quality of life using alternative models (Sulfonylurea Subgroup)
95%CI for β
95%CI for β
95%CI for β
−0.123 to −0.031
−9.606 to −3.456
−4.857 to 1.226
−0.107 to -0.013
−8.453 to −2.147
−2.973 to 3.084
−0.004 to −0.000
−0.243 to −0.038
−0.311 to −0.114
In patients with type 2 diabetes treated with antihyperglycemic therapy, hypoglycemia imposes a significant physical and psychological burden . Previously, we demonstrated that hypoglycemia is significantly associated with poorer HRQOL as well as increased fear of hypoglycemia . Other studies have shown an association between the severity of hypoglycemia and increased fear of hypoglycemia -. This retrospective analysis was conducted to test the hypothesis that fear of hypoglycemia is itself independently associated with poorer HRQOL. Results support this hypothesis, demonstrating a significant independent association between fear of hypoglycemia and scores on the EQ-5D and SF-12 PCS and MCS. This relationship was demonstrated for both insulin and sulfonylurea users. These results are consistent with previous cross sectional studies that have shown an association between fear of hypoglycemia and HRQOL ,.
A significant association was observed between symptomatic hypoglycemia and EQ-5D and SF-12 MCS scores in Model 1, whereas only the association with SF-12 MCS was significant after incorporating the HFS into the model. In contrast, fear of hypoglycemia demonstrated a significant association with all 3 HRQOL outcomes. This finding suggests that, statistically, fear of hypoglycemia may be a more important predictor than hypoglycemia itself of patient well-being and health status.
Multiple factors associated with fear of hypoglycemia were identified. Consistent with our study  and other reports ,,, symptomatic hypoglycemia had the strongest (positive) association with fear of hypoglycemia. Thus, it appears that in patients with type 2 diabetes, experiencing an event of hypoglycemia increases rather than diminishes fear of such an event. An important clinical practice implication of this finding is the need for healthcare professionals to be cognizant of the fear of hypoglycemia and take steps to address this fear and related behaviors.
In the current analysis, Hispanic/Latino ethnicity, duration of diabetes, and self-reported adherence also showed a positive association with fear of hypoglycemia, whereas household income and white race showed a negative association. These data suggest that demographic variables might be helpful in predicting those patients most likely to experience fear of hypoglycemia. The positive association between duration of diabetes and fear of hypoglycemia could reflect greater insulin use in patients with a longer duration of disease. Alternatively, an independent association between these variables would seem to further indicate that experiencing hypoglycemia increases fear of the event.
As no causality can be inferred in this cross-sectional analysis, the positive relationship between self-reported adherence and fear of hypoglycemia is difficult to interpret. In a previous study, patients reporting hypoglycemia symptoms were more likely to report barriers to adherence (eg, bothered by medication side effects, unable to follow plans) . In addition, data suggest that patients who have experienced a hypoglycemic episode are likely to initiate preventive behaviors that may include modification of their dosing regimen ,. Although these findings may seem at odds with one another, it is reasonable to expect that patients adherent to strict glycemic control regimens would have more reason to be fearful of hypoglycemia. Additional studies with longitudinal data collection are needed to fully understand the variables that predict fear of hypoglycemia.
Predictors of hypoglycemia in patients with type 2 diabetes are better understood. In the current analysis, more women versus men and more patients treated with OAD plus insulin versus sulfonylurea without insulin or nonsulfonylurea OAD without insulin reported hypoglycemia. The difference in hypoglycemia with respect to diabetes therapy is to be expected, given that insulin and insulin secretagogues are the most common cause of hypoglycemia in patients with type 2 diabetes . The observation that more women than men reported hypoglycemic symptoms was unexpected but has been observed in another study  and could possibly reflect sex-related differences in self-reporting of hypoglycemic symptoms.
This analysis has some limitations. Because the study was cross-sectional, no causal relationships can be inferred from the findings. Data on the frequency and severity of hypoglycemic episodes were not collected so their contribution to fear of hypoglycemia could not be assessed. Also, because the survey design used a convenience sample of patients that included only those who were members of specific health plans, with voluntary participation, survey participants may not be representative of all patients with type 2 diabetes. The study also relied on patient self-report, and the survey had a patient recall period of 6 months. Longitudinal cohort studies are warranted to further understand the impact of hypoglycemia and to test potential interventions to address the issue of hypoglycemia fear to improve health for patients with diabetes. In conclusion, in addition to symptomatic hypoglycemia itself, fear of hypoglycemia was independently associated with lower HRQOL (overall health status, mental health, and physical health) in patients with type 2 diabetes. There is an unmet need for patient education programs that address patient fear of hypoglycemia and use of medications with a lower risk of hypoglycemia.
The authors thank Vivian Fonseca, MD, for his helpful discussions during the development of this study. All authors contributed to the concept and design of the study; the acquisition, analysis, and interpretation of data; development of the statistical analysis plan; and review/editing of the manuscript for content. All authors had full access to the data included in the manuscript and approved the final version.
L.S. has received grants (to Tulane) from Novartis, Takeda, and Genentech and has received honoraria for consulting from AstraZeneca. N.A.T is an employee of Bristol-Myers Squibb. Y.Z. and H.S. report no potential conflicts. The study was sponsored by AstraZeneca (Wilmington, DE). Medical writing support for the preparation of this manuscript was provided by Deborah M. Campoli-Richards, BSPharm, RPh, Nicole Strangman, PhD, and Janet E. Matsuura, PhD, of Complete Healthcare Communications, Inc. (Chadds Ford, PA), with funding from Bristol-Meyers Squibb and AstraZeneca.
Data from this study were presented at the International Society for Pharmacoeconomics and Outcomes Research 18th Annual International Meeting, May 18–22, 2013, New Orleans, LA.
- Zhao Y, Campbell CR, Fonseca V, Shi L: Impact of hypoglycemia associated with antihyperglycemic medications on vascular risks in veterans with type 2 diabetes. Diabetes Care 2012, 35: 1126–1132. 10.2337/dc11-2048PubMed CentralView ArticlePubMedGoogle Scholar
- Zoungas S, Patel A, Chalmers J, De Galan BE, Li Q, Billot L, Woodward M, Ninomiya T, Neal B, MacMahon S, Grobbee DE, Pascal Kengne A, Marre M, Heller S: Severe hypoglycemia and risks of vascular events and death. N Engl J Med 2010, 363: 1410–1418. 10.1056/NEJMoa1003795View ArticlePubMedGoogle Scholar
- Hsu PF, Sung SH, Cheng HM, Yeh JS, Liu WL, Chan WL, Chen CH, Chou P, Chuang SY: Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study. Diabetes Care 2013, 36: 894–900. 10.2337/dc12-0916PubMed CentralView ArticlePubMedGoogle Scholar
- Alvarez Guisasola F, Tofe Povedano S, Krishnarajah G, Lyu R, Mavros P, Yin D: Hypoglycaemic symptoms, treatment satisfaction, adherence and their associations with glycaemic goal in patients with type 2 diabetes mellitus: findings from the Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) study. Diabetes Obes Metab 2008, 10: 25–32. 10.1111/j.1463-1326.2008.00882.xView ArticlePubMedGoogle Scholar
- Marrett E, Stargardt T, Mavros P, Alexander CM: Patient-reported outcomes in a survey of patients treated with oral antihyperglycaemic medications: associations with hypoglycaemia and weight gain. Diabetes Obes Metab 2009, 11: 1138–1144. 10.1111/j.1463-1326.2009.01123.xView ArticlePubMedGoogle Scholar
- Pollack MF, Purayidathil FW, Bolge SC, Williams SA: Patient-reported tolerability issues with oral antidiabetic agents: associations with adherence; treatment satisfaction and health-related quality of life. Diabetes Res Clin Pract 2010, 87: 204–210. 10.1016/j.diabres.2009.11.023View ArticlePubMedGoogle Scholar
- Green AJ, Fox KM, Grandy S: Self-reported hypoglycemia and impact on quality of life and depression among adults with type 2 diabetes mellitus. Diabetes Res Clin Pract 2012, 96: 313–318. 10.1016/j.diabres.2012.01.002View ArticlePubMedGoogle Scholar
- Williams SA, Pollack MF, Di Bonaventura M: Effects of hypoglycemia on health-related quality of life, treatment satisfaction and healthcare resource utilization in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2011, 91: 363–370. 10.1016/j.diabres.2010.12.027View ArticlePubMedGoogle Scholar
- Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR: Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012, 35: 1364–1379. 10.2337/dc12-0413PubMed CentralView ArticlePubMedGoogle Scholar
- Brunton SA: Hypoglycemic potential of current and emerging pharmacotherapies in type 2 diabetes mellitus. Postgrad Med 2012, 124: 74–83. 10.3810/pgm.2012.07.2570View ArticlePubMedGoogle Scholar
- Cryer PE: Hypoglycemia: still the limiting factor in the glycemic management of diabetes. Endocr Pract 2008, 14: 750–756. 10.4158/EP.14.6.750View ArticlePubMedGoogle Scholar
- Wild D, von Maltzahn R, Brohan E, Christensen T, Clauson P, Gonder-Frederick L: A critical review of the literature on fear of hypoglycemia in diabetes: implications for diabetes management and patient education. Patient Educ Couns 2007, 68: 10–15. 10.1016/j.pec.2007.05.003View ArticlePubMedGoogle Scholar
- Pettersson B, Rosenqvist U, Deleskog A, Journath G, Wandell P: Self-reported experience of hypoglycemia among adults with type 2 diabetes mellitus (Exhype). Diabetes Res Clin Pract 2011, 92: 19–25. 10.1016/j.diabres.2010.12.005View ArticlePubMedGoogle Scholar
- Leiter LA, Yale J, Chiasson J, Harris S, Kleinstiver P, Sauriol L: Assessment of the impact of fear of hypoglycemic episodes on glycemic and hypoglycemia management. Can J Diabetes 2005, 29: 186–192.Google Scholar
- Amiel SA, Dixon T, Mann R, Jameson K: Hypoglycaemia in type 2 diabetes. Diabet Med 2008, 25: 245–254. 10.1111/j.1464-5491.2007.02341.xPubMed CentralView ArticlePubMedGoogle Scholar
- Williams SA, Shi L, Brenneman SK, Johnson JC, Wegner JC, Fonseca V: The burden of hypoglycemia on healthcare utilization, costs, and quality of life among type 2 diabetes mellitus patients. J Diabetes Complications 2012, 26: 399–406. 10.1016/j.jdiacomp.2012.05.002View ArticlePubMedGoogle Scholar
- Morisky DE, Green LW, Levine DM: Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care 1986, 24: 67–74. 10.1097/00005650-198601000-00007View ArticlePubMedGoogle Scholar
- Cox DJ, Irvine A, Gonder-Frederick L, Nowacek G, Butterfield J: Fear of hypoglycemia: quantification, validation, and utilization. Diabetes Care 1987, 10: 617–621. 10.2337/diacare.10.5.617View ArticlePubMedGoogle Scholar
- Matza LS, Boye KS, Yurgin N: Validation of two generic patient-reported outcome measures in patients with type 2 diabetes. Health Qual Life Outcomes 2007, 5: 47. 10.1186/1477-7525-5-47PubMed CentralView ArticlePubMedGoogle Scholar
- What is EQ-5D? In ., [http://www.euroqol.org]
- Ware J Jr, Kosinski M, Keller SD: A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996, 34: 220–233. 10.1097/00005650-199603000-00003View ArticlePubMedGoogle Scholar
- Living with diabetes. In , [http://www.diabetes.org/living-with-diabetes/treatment-and-care/blood-glucose-control/hypoglycemia-low-blood.html]
- SAS Institute Inc: SAS/STAT® User’s Guide. Version 9.2. SAS Institute Inc, Cary, NC; 2008.Google Scholar
- Wrobel MP, Wystrychowski G, Psurek A, Szymborska-Kajanek A, Strojek K: Association between hypoglycemia and the type of insulin in diabetic patients treated with multiple injections: an observational study. Pol Arch Med Wewn 2014, 124: 173–179.PubMedGoogle Scholar
- Pitsillides AN, Anderson SM, Kovatchev B: Hypoglycemia risk and glucose variability indices derived from routine self-monitoring of blood glucose are related to laboratory measures of insulin sensitivity and epinephrine counterregulation. Diabetes Technol Ther 2011, 13: 11–17. 10.1089/dia.2010.0103PubMed CentralView ArticlePubMedGoogle Scholar
- Kalra S, Deepak MC, Narang P, Singh V, Maheshwari A: Correlation between measures of hypoglycemia and glycemic improvement in sulfonylurea treated patients with type 2 diabetes in India: results from the OBSTACLE hypoglycemia study. J Postgrad Med 2014, 60: 151–155. 10.4103/0022-3859.132322View ArticlePubMedGoogle Scholar
- Odawara M, Kadowaki T, Naito Y: Incidence and predictors of hypoglycemia in Japanese patients with type 2 diabetes treated by insulin glargine and oral antidiabetic drugs in real-life: ALOHA post-marketing surveillance study sub-analysis. Diabetol Metab Syndr 2014, 6: 20. 10.1186/1758-5996-6-20PubMed CentralView ArticlePubMedGoogle Scholar
- Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, Heller SR, Rodriguez H, Rosenzweig J, Vigersky R: Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and The Endocrine Society. Diabetes Care 2013, 36: 1384–1395. 10.2337/dc12-2480PubMed CentralView ArticlePubMedGoogle Scholar
- Marrett E, Radican L, Davies MJ, Zhang Q: Assessment of severity and frequency of self-reported hypoglycemia on quality of life in patients with type 2 diabetes treated with oral antihyperglycemic agents: a survey study. BMC Res Notes 2011, 4: 251. 10.1186/1756-0500-4-251PubMed CentralView ArticlePubMedGoogle Scholar
- Sheu WH, Ji LN, Nitiyanant W, Baik SH, Yin D, Mavros P, Chan SP: Hypoglycemia is associated with increased worry and lower quality of life among patients with type 2 diabetes treated with oral antihyperglycemic agents in the Asia-Pacific region. Diabetes Res Clin Pract 2012, 96: 141–148. 10.1016/j.diabres.2011.12.027View ArticlePubMedGoogle Scholar
- Stargardt T, Gonder-Frederick L, Krobot KJ, Alexander CM: Fear of hypoglycaemia: defining a minimum clinically important difference in patients with type 2 diabetes. Health Qual Life Outcomes 2009, 7: 91. 10.1186/1477-7525-7-91PubMed CentralView ArticlePubMedGoogle Scholar
- Solli O, Stavem K, Kristiansen IS: Health-related quality of life in diabetes: the associations of complications with EQ-5D scores. Health Qual Life Outcomes 2010, 8: 18. 10.1186/1477-7525-8-18PubMed CentralView ArticlePubMedGoogle Scholar
- Mitchell BD, Vietri J, Zagar A, Curtis B, Reaney M: Hypoglycaemic events in patients with type 2 diabetes in the United Kingdom: associations with patient-reported outcomes and self-reported HbA1c. BMC Endocr Disord 2013, 13: 59. 10.1186/1472-6823-13-59PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.