INTRODUCTIONDiabetes is associated with a number of complications of differing duration, complexity and severity that can occur during the management of blood glucose levels. This module is intended to develop understanding of the short term complications of diabetes – 'hypos and hypers' – and their implications for morbidity and mortality.
LEARNING OBJECTIVESOn completion of this module, you will:
This module is one of a series of five. Others in the series are:
Short-term complications of type 2 diabetesType 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 stateThere are two hyperglycaemic emergencies in diabetes:
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 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.3,4 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.4 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.4 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.5 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.5 Hyperosmolar hyperglycaemic state (HHS) is also a life-threatening condition.6 HSS is characterised by severe hyperglycaemia (often over 40 mmol/L), without evidence of significant ketosis.6.7 Hyperglycaemia causes osmotic 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.7 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.7 As in DKA, HHS may also be associated with acute illness, i.e. infection (most commonly pneumonia or urinary tract infection) or myocardial infarction.7 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.7 Treatment consists of fluid replacement, electrolyte replacement, insulin to reduce glucose levels, and detection and treatment of the underlying cause.7 Mortality from HHS is high, with reported death rates of 15-20%.8 Immediate and longer term management of DKA or HHSPeople 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.4,7 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.8 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).5 Symptoms and management of hypoglycaemic eventsHypoglycaemia 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.9,10 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.2,11,12 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.13 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.14 Treatment of hypoglycaemia normally involves taking:
Consider following this with:
Followed by
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.15,16 Sick Day RulesIn 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 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.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.
References 1. Diabetes UK. Guide to diabetes: Testing. https://www.diabetes.org.uk/Guide-to-diabetes/Managing-your-diabetes/Testing 2. Diabetes UK. Guide to diabetes: Hypos. https://www.diabetes.org.uk/guide-to-diabetes/complications/hypos 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. BMJ. Best Practice: Diabetic ketoacidosis, May 2016. https://bestpractice.bmj.com/best-practice/monograph/162/diagnosis/criteria.html 5. 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 6. Diabetes UK. Hyperglycaemic hyperosmolar State (HHS). https://www.diabetes.org.uk/guide-to-diabetes/complications/hyperosmolar_hyperglycaemic_state_hhs 7. Patient. Hyperosmolar hyperglycaemic state, 2015. https://patient.info/doctor/hyperosmolar-hyperglycaemic-state 8. 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 9. Diabetes UK. Hypoglycaemia unawareness. https://www.diabetes.org.uk/guide-to-diabetes/complications/hypos/hypo-unawareness 10. Patient. Hypoglycaemia, 2016. https://patient.info/doctor/hypoglycaemia 11. Diabetes.co.uk. Insulin overdose; 2019. https://www.diabetes.co.uk/insulin/insulin-overdosage.html 12. Diabetes.co.uk. Diabetes and hot weather. https://www.diabetes.co.uk/diabetes-and-hot-weather.html 13. NICE NG28. Type 2 diabetes in adults: management, 2015 (Updated 2022) https://www.nice.org.uk/guidance/ng28 14. 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 15. British National Formulary. Treatment of hypoglycaemia. https://bnf.nice.org.uk/treatment-summary/hypoglycaemia.html 16. British National Formulary. Glucagon. https://bnf.nice.org.uk/drug/glucagon.html 17. GP Notebook. Sick day rules - type 2 diabetes; 2020. https://gpnotebook.com/simplepage.cfm?ID=x2017060421413191130 18. Diabetes.co.uk. Diabetes and hyperglycaemia. https://www.diabetes.co.uk/Diabetes-and-Hyperglycaemia.html |
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