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Table of Contents
COMMENTARY
Year : 2021  |  Volume : 4  |  Issue : 1  |  Page : 2-3

Identifying and treating hypoglycemia in insulin-treated diabetes


The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, UK

Date of Submission26-Mar-2021
Date of Acceptance26-Mar-2021
Date of Web Publication13-Apr-2021

Correspondence Address:
Prof. Brian M Frier
The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, Scotland
UK
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdep.jdep_11_21

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How to cite this article:
Frier BM. Identifying and treating hypoglycemia in insulin-treated diabetes. J Diabetes Endocr Pract 2021;4:2-3

How to cite this URL:
Frier BM. Identifying and treating hypoglycemia in insulin-treated diabetes. J Diabetes Endocr Pract [serial online] 2021 [cited 2021 Jun 15];4:2-3. Available from: https://www.jdeponline.com/text.asp?2021/4/1/2/313674



Hypoglycemia is the most common side effect of treatment with insulin and to a lesser extent is associated with the use of insulin secretagogues such as the sulfonylureas. While generally unpleasant and inconvenient, most episodes of hypoglycemia are readily self-treated and pose little risk to the individual, unless they are performing a complex task such as driving. However, severe hypoglycemia, defined by requiring help for recovery, causes significant cognitive impairment and can be associated with significant morbidity or even be life threatening. Early identification of the onset of hypoglycemia, which was redefined recently as a blood glucose of <3.0 mmol/L (54 mg/dL),[1] is therefore essential if appropriate action is to be taken by the affected individual or by carers to avoid progression to severe hypoglycemia.

Hypoglycemia (severe and nonsevere) is three times more frequent in people with Type 1 diabetes than in those with insulin-treated Type 2 diabetes.[2] Severe events are experienced by 30%–40% of adults with Type 1 diabetes annually and in around 20%–25% of people with insulin-treated Type 2 diabetes.[3],[4] The large global HAT study (Hypoglycemia Among insulin-Treated patients with diabetes) demonstrated that the frequency of severe hypoglycemia is much higher in Type 2 diabetes than had been appreciated previously,[5] and the rates in HAT are consistent with those reported by other real-world studies of hypoglycemia in insulin-treated Type 2 diabetes.[6] Many people with Type 2 diabetes progress to insulin dependence with time, and the frequency of hypoglycemia increases with duration of insulin therapy.[3] In Middle Eastern countries where Type 2 diabetes predominates, the frequency of hypoglycemia is therefore likely to be escalating, because of increasing longevity of people with Type 2 diabetes, the rising need for insulin replacement therapy, and the overall improvement in glycemic control associated with intensification of therapy.

Two papers in the present issue of the journal are of relevance to the burgeoning problem of hypoglycemia in the Middle East. One highlights the current lack of knowledge about hypoglycemia within a population who have mainly Type 2 diabetes and the other describes a novel and user-friendly method of delivering glucagon to treat severe hypoglycemia that can be used both in community and hospital settings.

A questionnaire study in Saudi Arabia of 361 adults with diabetes, 95% of whom had Type 2 diabetes, and 40% of whom were receiving insulin therapy, has demonstrated that knowledge about hypoglycemia and the management of this problem is limited, and this included the identification of the symptoms, the causes, treatment options, and ways to avoid developing a low blood glucose.[7] As people with diabetes who were being treated with diet alone or with oral glucose-lowering medications (with the exception of sulfonylureas) would seldom have encountered hypoglycemia, their lack of knowledge of hypoglycemia in the survey is not surprising. However, the deficiencies in knowledge in those treated with insulin are disturbing and suggest that their education about hypoglycemia has either been inadequate or was poorly understood by the patients. Whatever the reason, this suggests that a serious communication gap exists between many patients and their health-care providers (HCPs). The latter have a responsibility to discuss hypoglycemia during routine consultations, but surveys of insulin-treated patients in Europe have demonstrated that HCPs seldom review, or even mention, hypoglycemia.[8],[9] This lack of focus on hypoglycemia and evidence of deficiencies in education about its recognition and management, particularly in people with Type 2 diabetes, is a widespread phenomenon and not one confined to Saudi Arabia. Educational deficiencies are particularly problematical in older people and their relatives, whose ability to identify and manage hypoglycemia has been shown to be very limited[10] and if they have some degree of cognitive impairment, education about hypoglycemia needs to be reinforced regularly. This problem is easily overlooked in specialist care when several other medical issues, such as diabetic complications, may be demanding attention. The present study observed that younger people and particularly those who had experienced hypoglycemia previously were better informed about the presentation, causes, and treatment of this side effect of insulin. Regular discussion about hypoglycemia is essential in all people receiving insulin and the provision of information about hypoglycemia should be a fundamental part of the diabetes education package, which may have to be repeated and updated at intervals.

Severe hypoglycemia is a serious medical emergency that requires urgent treatment and may be associated with coma and/or seizures. The methods of treating severe hypoglycemia have been reviewed recently.[11] When a person with severe hypoglycemia is comatose or is semi-conscious but profoundly neuroglycopenic and unable to swallow, the usual rescue treatment is to inject either intravenous dextrose or intramuscular (i.m.) glucagon. The parenteral administration of glucose requires intervention by medical or paramedical staff and is not an option for lay people who are required to treat severe hypoglycemia in the community, which is where most severe episodes are managed.[12] Although glucagon is a long-standing and well-established rescue treatment for severe hypoglycemia and is provided in emergency kits that can be kept at home, it is not an easy preparation to use and has to be given by injection. Immediate reconstitution of a powdered form of glucagon is necessary by dissolving it in a diluent to allow its injection as a solution.[10] Thus, the parenteral administration of glucagon requires several careful steps to be followed, often by a person who is inexperienced in administering medications by injection and who is confronted by a stressful situation that is prone to induce panic and distress. A clumsy procedure leads to mistakes and inadequate administration of glucagon.

In the present issue, Heba et al. have reviewed a novel form of glucagon that is now available to treat severe hypoglycemia.[13] A different route of delivery has been developed for glucagon to be administered into the nose. The drug is available in the form of a dry powder (3 mg) that is introduced into a nostril using a single-use puffer device and is passively absorbed through the nasal mucosa with no need for the recipient to inhale. When compared with i.m. glucagon, it is approximately 3 min slower in restoring normoglycemia, which is not considered to be clinically relevant.[11] It can be used successfully in the presence of nasal congestion or rhinorrhea such as when a person has an upper respiratory infection such as a common cold.[14] It is therefore as effective as i.m. glucagon and the principal benefit of nasal glucagon is the ease of administration with no skill being required and with no need for reconstitution before administration. Family members, who live with the fear of having to manage unpredictable episodes of severe hypoglycemia in a relative (especially the parents of young children) and carers who look after patients with insulin-treated diabetes, are much more confident in giving nasal glucagon to treat severe hypoglycemia and less likely to make mistakes.[11] This product simplifies the treatment of a serious metabolic emergency and so represents a significant therapeutic advance.

Authors' contribution

Single author.

Sponsorship and funding

Nil.

Conflict of interest

Nil.

Compliance with ethical principles

No ethical approval is required.



 
  References Top

1.
International Hypoglycaemia Study Group. Glucose concentrations of less than 3.0 mmol/L (54 mg/dL) should be reported in clinical trials: A joint position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2017;40:155-7.  Back to cited text no. 1
    
2.
Frier BM. Hypoglycaemia in diabetes mellitus: Epidemiology and clinical implications. Nat Rev Endocrinol 2014;10:711-22.  Back to cited text no. 2
    
3.
UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: Effects of treatment modalities and their duration. Diabetologia 2007;50:1140-7.  Back to cited text no. 3
    
4.
Edridge CL, Dunkley AJ, Bodicoat DH, Rose TC, Gray LJ, Davies MJ, et al. Prevalence and incidence of hypoglycaemia in 532,542 people with type 2 diabetes on oral therapies and insulin: A systematic review and meta-analysis of population based studies. PLoS One 2015;10:e0126427.  Back to cited text no. 4
    
5.
Khunti K, Alsifri S, Aronson R, Cigrovski Berković M, Enters-Weijnen C, Forsén T, et al. Rates and predictors of hypoglycaemia in 27 585 people from 24 countries with insulin-treated type 1 and type 2 diabetes: The global HAT study. Diabetes Obes Metab 2016;18:907-15.  Back to cited text no. 5
    
6.
Pedersen-Bjergaard U, Alsifri S, Aronson R, Berković MC, Galstyan G, Gydesen H, et al. Comparison of the HAT study, the largest global hypoglycaemia study to date, with similar large real-world studies. Diabetes Obes Metab 2019;21:844-53.  Back to cited text no. 6
    
7.
Al Zahrani AM, Al-Zaidi S, Al Shaikh A, Alghamdi A, Farahat F. Lack of knowledge about hypoglycemia among adult patients with diabetes mellitus in Saudi Arabia: A cross-sectional study. J Diabetes Endocr Pract 2021;4:37-42.  Back to cited text no. 7
    
8.
Östenson CG, Geelhoed-Duijvestijn P, Lahtela J, Weitgasser R, Markert Jensen M, Pedersen-Bjergaard U. Self-reported non-severe hypoglycaemic events in Europe. Diabet Med 2014;31:92-101.  Back to cited text no. 8
    
9.
Frier BM, Jensen MM, Chubb BD. Hypoglycaemia in adults with insulin-treated diabetes in the UK: Self-reported frequency and effects. Diabet Med 2016;33:1125-32.  Back to cited text no. 9
    
10.
McAulay V, Deary IJ, Frier BM. Symptoms of hypoglycaemia in people with diabetes. Diabet Med 2001;18:690-705.  Back to cited text no. 10
    
11.
Thieu VT, Mitchell BD, Varnado OJ, Frier BM. Treatment and prevention of severe hypoglycaemia in people with diabetes: Current and new formulations of glucagon. Diabetes Obes Metab 2020;22:469-79.  Back to cited text no. 11
    
12.
Donnelly LA, Morris AD, Frier BM, Ellis JD, Donnan PT, Durrant R, et al. Frequency and predictors of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: A population-based study. Diabet Med 2005;22:749-55.  Back to cited text no. 12
    
13.
Heba SF, Parveen U, Khanum SS, Gulnaaz M, Tabassum M, Safiyya SB. Nasal. Inhaled glucagon: A new hope for severe hypoglycemia in type 1 diabetes. J Diabetes Endocr Pract 2021;4:14-19.  Back to cited text no. 13
    
14.
Guzman CB, Dulude H, Piché C, Rufiange M, Sadoune AA, Rampakakis E, et al. Effects of common cold and concomitant administration of nasal decongestant on the pharmacokinetics and pharmacodynamics of nasal glucagon in otherwise healthy participants: A randomized clinical trial. Diabetes Obes Metab 2018;20:646-53.  Back to cited text no. 14
    




 

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