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Job Code: PC-GB-102836                         Date of preparation: March 2021



This promotional module has been initiated, funded and reviewed by Boehringer Ingelheim. The content of this industry-supported learning activity has been generated by Practice Nurse.

 

INTRODUCTION

This module is intended to develop the general practice nurse’s understanding of the short-term complications of type 2 diabetes – ‘hypos and hypers’ – and their implications for morbidity and mortality.

The module covers:

  • Diabetic ketoacidosis (DKA): definition, diagnosis, causes and management
  • Hyperosmolar hyperglycaemic state (HHS): definition, diagnosis, causes and management
  • Hypoglycaemia (hypos): definition, diagnosis, causes and management
  • Sick day rules

LEARNING OBJECTIVES

On completion of this module, the general practice nurse will:

  • Be familiar with the causes, signs, symptoms of DKA and HHS
  • Be aware of the significance of DKA in undiagnosed patients, especially children
  • Recognise that DKA and HHS are medical emergencies, which require urgent hospital admission for intensive management
  • Be able to describe the symptoms of hypoglycaemic events, their immediate management, and the minimisation of hypo risk through appropriate prescribing
  • Be able to offer appropriate advice on the prevention of these complications
  • Be familiar with the sick day rules

This module is one of a series of five. Others in the series are:

Short-term complications of type 2 diabetes

Type 2 diabetes requires lifestyle and pharmacological interventions to achieve blood glucose levels which are as close as possible to those seen in people without diabetes. However, this requires careful balancing of food intake, activity levels and medication, and high glucose levels (hyperglycaemia) and low glucose levels (hypoglycaemia) are too often seen. According to Diabetes UK, hyperglycaemia is defined as a pre-meal blood glucose reading higher than 7 mmol/l, or a 2 hour post-prandial reading of above 8.5mmol/l for people with type 2 diabetes.1 Hypoglycaemia is present when blood glucose levels are less than 4.0mmol/l.2 These short term complications of diabetes can increase the risk of developing serious complications.1

Hyperglycaemia, diabetic ketoacidosis and hyperosmolar hyperglycaemic state

There are two hyperglycaemic emergencies in diabetes:

  • Diabetic ketoacidosis
  • Hyperosmolar hyperglycaemic state previously known as hyperosmolar non-ketotic coma (HONK)

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes. While DKA is a commonly recognised risk in autoimmune diabetes, stressful conditions such as trauma, surgery, or infection also increase DKA risk in patients with type 2 diabetes.3 Studies have reported that patients with type 2 diabetes account for 12-56% of DKA cases.3-5

Reduced insulin concentration or action, along with increased counter-regulatory hormones, lead to the hyperglycaemia volume depletion and electrolyte imbalance that underlie the pathophysiology of DKA.6 As a result of the inadequate levels of insulin, cells are unable to use glucose as an energy source, and use the body's fat reserves instead. Glucose levels rise (to over 11.1 mmol/l in adults) and ketones, a by-product of fat metabolism, also rise (to over 3.0 mmol/l) causing the blood to become more acidic than usual – a process known as ketoacidosis.6

In acute illness, the body’s metabolism speeds up and works harder to deal with the illness, and will use glycogen and break down fats to maintain energy levels, thus producing ketones.

The signs and symptoms of DKA include nausea or vomiting, stomach pain, excessive thirst, fast and deep breathing, confusion, unusual sleepiness or tiredness, and acetone breath. Those who develop DKA need urgent hospital treatment to prevent and/or treat cerebral oedema, a serious complication, which is the most common cause of mortality in DKA.6

Rare cases of DKA, including life-threatening cases, have occurred in patients with type 2 diabetes who are taking SGLT2 inhibitors, and a number of these cases have been atypical, with patients not having blood glucose levels as high as expected.7  Healthcare professionals have been recommended to consider the possibility of ketoacidosis in patients taking SGLT2 inhibitors who have symptoms consistent with the condition, even if their blood glucose levels are not high.7

Hyperosmolar hyperglycaemic state (HSS) is also a life-threatening condition.8 HSS is characterised by severe hyperglycaemia (often over 40 mmol/l), without evidence of significant ketosis.8,9 Hyperglycaemia causes osmostic diuresis, leading to hyperosmolarity resulting in severe intracellular dehydration. Ketosis does not occur due to the presence of basal insulin secretion, sufficient to prevent ketogenesis but not enough to reduce blood glucose.9 The risk of HHS increases in people with dehydration and renal impairment, and is more prevalent in the elderly, especially those who are housebound or living in residential care.9

As in DKA, HHS may also be associated with acute illness, i.e. infection (most commonly pneumonia or urinary tract infection) or myocardial infarction.9

People with HHS are usually drowsy, confused or even unconscious and therefore should be treated as a medical emergency. Prior to this, they may have experienced symptoms such as general malaise, myalgia, cramps, or vision changes. Nausea and vomiting may also be present but less so than in DKA.9

Treatment consists of fluid replacement, electrolyte replacement, insulin to reduce glucose levels, and detection and treatment of the underlying cause.9 Mortality from HHS is high, with reported death rates of 15-20%.10

Immediate and longer term management of DKA or HHS

People with DKA or HHS need urgent admission to hospital to prevent further harm including death. Following admission treatment will include infusions of both insulin and fluids.6,9

In DKA, insulin is given to reduce excess circulating blood glucose levels and stop the body from breaking down fats for energy thus correcting ketoacidosis. Fluid replacement is used to rehydrate the individual. In HHS, insulin treatment should be administered cautiously, if fluid replacement has not reduced blood glucose levels.10 Following recovery an assessment of the cause of the episode should be carried out to avoid further episodes.

Causes of hyperglycaemia include dietary indiscretions, including intake of too much carbohydrate; acute illness; omitting to take medication including insulin; inadequate review of diabetes; and medication, e.g. SGLT2 inhibitors (rare).7

Symptoms and management of hypoglycaemic events

Hypoglycaemia is where the blood glucose level is less than 4.0mmol/l,2 although some people are less aware – or even unaware – of the symptoms of hypoglycaemia, particularly in those individuals who have had persistently raised glucose levels for some time.11,12

Causes of hypoglycaemia include too much medication, including insulin; missed, delayed or inadequate meals; increased activity levels; hot weather (causing increased absorption of insulin and possible dehydration); and administration errors in people using insulin therapy.2,13 As with hyperglycaemia, the patient should be encouraged to determine the cause of the hypoglycaemic event in order to avoid it happening again.

There are two key classes of medication that may cause hypoglycaemia – sulfonylureas (SUs) and insulin. NICE recommends insulin as an option for patients with type 2 diabetes whose blood glucose levels remain uncontrolled on two oral hypoglycaemic agents.14 In these patients, injection technique and assessment for lipodystrophy will be a key priority. People who are on an SU who experience frequent hypos should be reviewed to see whether other types of glucose lowering agents with a lower risk of hypoglycaemia should be initiated instead. Drug classes associated with a lower risk of hypoglycaemia include pioglitazone, DPP-4 inhibitors, SGLT2 inhibitors and GLP-1 receptor agonists.15

Treatment of hypoglycaemia normally involves taking:

  • 15-20g of quick acting carbohydrate e.g. 3-4 heaped teaspoonfuls of sugar dissolved in a small glass of water, 4–7 glucose tablets, small carton of fruit juice (150–200ml), or proprietary fast acting carbohydrate, e.g. Glucogel. A tube of contains 10g of quick acting carbohydrate. One or two tubes may be required.16

Consider following this with:

  • A longer acting carbohydrate e.g. biscuits/bread/cereal

Followed by

  • A 10-15 minute wait and then retest. If the reading is still below 4mmol/l repeat the process and get help.16

In severe cases, Glucagon 1mg can be injected. The individual should be assessed following administration and if there is no response after 10 minutes the patient will need intravenous glucose. This is a medical emergency. However, if there is a response and the patient is able to swallow, this should be backed up with a longer acting carbohydrate.16

Sick Day Rules

In the event of an acute illness, people with diabetes and their carers should be able to understand and implement the 'sick day' rules. Acute illness may lead to a rise in blood glucose levels with the potential for dehydration, especially if the individual has a temperature. As a result, people with diabetes should ensure they have an adequate sugar-free fluid intake (around 3 litres) and take medication as they normally would, with some exceptions. In type 2 diabetes metformin and SGLT2 inhibitors should be stopped (temporarily) if the patient has vomiting or diarrhoea, as the risk of dehydration is increased and can lead to significant side effects.17 Patients can be advised to restart these medications when they are well (usually after 24 - 48 hours of eating and drinking normally.)17 Patients on insulin should not stop taking it, even if they are ill and cannot eat. Insulin dose adjustment may be required, depending on blood glucose levels. Patients should therefore be advised to increase the frequency of blood glucose monitoring and to contact a healthcare professional if their blood glucose levels are persistently >25 mmol/mol.17

In the self-assessment that follows, hypothetical case scenarios based on fictitious patients are presented. Please refer to the relevant Summary of Product Characteristics before prescribing any of the medications mentioned. 

Please note, neither Practice Nurse nor Boehringer Ingelheim is responsible for the content of any of the external websites listed in the references below. 

References

1. Diabetes UK. Guide to diabetes: Testing. https://www.diabetes.org.uk/Guide-to-diabetes/Managing-your-diabetes/Testing [Accessed March 2021]

2. Diabetes UK. Guide to diabetes: Hypos. https://www.diabetes.org.uk/guide-to-diabetes/complications/hypos [Accessed March 2021]

3. Wang Y et al. Incidence of diabetic ketoacidosis among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors and other antihyperglycemic agents. Diabetes Res Clin Pract. 2017 Jun;128:83-90.

4. Xu Y, Bai J, Wang G, et al. Clinical profile of diabetic ketoacidosis in tertiary hospitals in China: a multicentre, clinic-based study. Diabet Med 2016;33(2):261-8

5. Barski L, Nevzorov R, Jotkowitz A, et al. Comparison of diabetic ketoacidoses in patients with type-1 and type-2 diabetes mellitus. Am J Med Sci 2013;345(4):326-30

6. BMJ. Best Practice: Diabetic ketoacidosis, May 2016. https://bestpractice.bmj.com/best-practice/monograph/162/diagnosis/criteria.html [Accessed March 2021]

7. European Medicines Agency. EMA confirms recommendations to minimise ketoacidosis risk with SGLT2 inhibitors for diabetes; 2016. https://www.ema.europa.eu/en/medicines/human/referrals/sglt2-inhibitors [Accessed March 2021]

8. Diabetes UK. Hyperglycaemic hyperosmolar State (HHS). https://www.diabetes.org.uk/guide-to-diabetes/complications/hyperosmolar_hyperglycaemic_state_hhs [Accessed March 2021]

9. Patient. Hyperosmolar hyperglycaemic state, 2015. https://patient.info/doctor/hyperosmolar-hyperglycaemic-state [Accessed March 2021]

10. Joint British Diabetes Societies. The management of hyperosmolar hyperglycaemic state (HHS) in adults with diabetes, 2012. https://abcd.care/sites/abcd.care/files/resources/JBDS_IP_HHS_Adults.pdf [Accessed March 2021]

11. Diabetes UK. Hypoglycaemia unawareness. https://www.diabetes.org.uk/guide-to-diabetes/complications/hypos/hypo-unawareness [Accessed March 2021]

12. Patient. Hypoglycaemia, 2016. https://patient.info/doctor/hypoglycaemia [Accessed March 2021]

13. Diabetes.co.uk. Insulin overdose; 2019. https://www.diabetes.co.uk/insulin/insulin-overdosage.html [Accessed March 2021]

14. NICE NG28. Type 2 diabetes in adults: management, 2015 (Updated 2019) https://www.nice.org.uk/guidance/ng28 [Accessed March 2021]

15. Davies MJ, D’Alessio DA, Fradkin F, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41:2669-2701

16. British National Formulary. Treatment of hypoglycaemia. https://bnf.nice.org.uk/treatment-summary/hypoglycaemia.html [Accessed March 2021]

17. GP Notebook. Sick day rules - type 2 diabetes; 2020. https://gpnotebook.com/simplepage.cfm?ID=x2017060421413191130 [Accessed March 2021]


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