2018 Clinical Practice Guidelines Hypoglycemia Chapter 14 Jean-François Yale MD FRCPC Breay Paty MD FRCPC Peter Senior MD FRCPC 1

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2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Key Changes 2018 Reinforcement of the importance of counselling individuals on insulin or insulin secretagogues and their support persons on the risk, prevention, recognition and treatment of hypoglycemia New information on strategies to reduce the risk of hypoglycemia

Hypoglycemia Checklist 2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Hypoglycemia Checklist RECOGNIZE hypoglycemia and CONFIRM DIFFERENTIATE mild-moderate vs. severe TREAT hypoglycemia but AVOID OVERTREAMENT AVOID hypoglycemia in the future 4

Definition of Hypoglycemia 2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Definition of Hypoglycemia Development of neurogenic or neuroglycopenic symptoms Low blood glucose (<4 mmol/L if on insulin or secretagogue) Response to carbohydrate load Neurogenic (autonomic) Neuroglycopenic Trembling Difficulty Concentrating Palpitations Confusion Sweating Weakness Anxiety Drowsiness Hunger Vision Changes Nausea Difficulty Speaking Dizziness The CDA defines hypoglycemia as the development of autonomic (trembling, palpitations, sweating, anxiety, hunger, nausea, tingling) or neuroglycopenic (difficulty concentrating, confusion, weakness, drowsiness, vision changes, difficulty speaking, headache, dizziness) symptoms, a low plasma glucose, and symptoms responding to the administration of a carbohydrate. In mild to moderate hypoglycemia, blood glucose is <4 mmol/L, autonomic and/or neuroglycopenic symptoms are present, but the patient is able to self-treat. However, patients who maintain a higher blood glucose level may experience hypoglycemia at levels >4.0 mmol/L. Severe hypoglycemia indicates the patient is unable to treat the reaction without outside assistance. He/she may or may not be conscious. 5

Severity of Hypoglycemia 2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Severity of Hypoglycemia Mild Autonomic symptoms present Individual is able to self-treat Moderate Autonomic and neuroglycopenic symptoms Individual is able to self-treat Severe Requires the assistance of another person Unconsciousness may occur Plasma glucose is typically <2.8 mmol/L The characteristics for the clinical presentation of hypoglycemia vary depending on the severity of the episode. In cases of mild hypoglycemia, autonomic symptoms (eg trembling, sweating, hunger, palpitations etc) are usually present and the patient is able to self-treat. When the hypoglycemic episode is moderate, in addition to the presence of autonomic symptoms, there are also neuroglycopenic symptoms (eg confusion, dizziness, weakness, difficulty concentrating etc) and the patient is still able to self-treat. When the hypoglycemic episode is severe, both autonomic and neruoglycopenic symptoms are present however at this stage the patient is not able to self-treat and requires the assistance of another person. During this stage the presence of unconsciousness may occur (eg diabetic coma and seizure). Hypoglycemia unawareness can develop during the moderate or severe hypoglycemic episodes and it is usually characterized by the presence of cognitive symptoms in the absence of autonomic symptoms. Age, duration of diabetes and previous hypoglycemic episodes can all lead to the development of hypoglycemic unawareness. 6

Prior episode of severe hypoglycemia Current low A1C (<6.0%) 2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Risk factors for severe hypoglycemia in people treated with sulfonylureas or insulin Prior episode of severe hypoglycemia Current low A1C (<6.0%) Hypoglycemia unawareness Long duration of insulin therapy Autonomic neuropathy Chronic kidney disease Low economic status, food insecurity Low health literacy Preschool-age children unable to detect and/or treat mild hypoglycemia on their own Adolescence Pregnancy Elderly Cognitive impairment

Drug Induced Hypoglycemia 2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Drug Induced Hypoglycemia Can result in significant morbidity and mortality Serious obstacle to meet glycemic targets Counsel patients who drive on insulin or secretagogues re: SMBG and taking appropriate precautions Script: Drug-induced hypoglycemia can be severe and result in confusion, coma, or seizure requiring the assistance of other individuals. Frequency and severity of hypoglycemia negatively impacts on quality of life (1) and promotes fear of future hypoglycemia which can be a major obstacle for individuals trying to achieve glycemic targets. It is essential to counsel patients who are on insulin or secretagogues re: SMBG and taking appropriate precautions prior to driving. SMBG, self-monitoring of blood glucose 8

Steps to Address Hypoglycemia 2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Steps to Address Hypoglycemia Recognize autonomic or neuroglycopenic symptoms Confirm if possible (blood glucose <4.0 mmol/L) Treat with “fast sugar” (simple carbohydrate) (15 g) to relieve symptoms Retest in 15 minutes to ensure the BG >4.0 mmol/L and retreat (see above) if needed Eat usual snack or meal due at that time of day or a snack with 15 g carbohydrate plus protein Teaching patients to recognize and treat hypoglycemia can be done in 3 steps 1) It is important to teach patients to recognize the common autonomic and neuroglycopenic symptoms associated with hypoglycemia including: Trembling, Palpitations, Sweating, Anxiety, Hunger, Nausea, Tingling which are common autonomic symptoms and Difficulty concentrating, Confusion, Weakness, Vision change, and Headache are common neuroglycopenic symptoms. 9

Examples of 15 g Simple Carbohydrate 2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Examples of 15 g Simple Carbohydrate 15 g of glucose in the form of glucose tablets 15 mL (3 teaspoons) or 3 packets of sugar dissolved in water 150 mL of juice or regular soft drink 6 Lifesavers (1 = 2.5 g of carbohydrate) 15 mL (1 tablespoon) of honey : Evidence suggests that 15 g of glucose (monosaccharide) is required to produce an increase in BG of approximately 2.1 mmol/L within 20 minutes, with adequate symptom relief for most people 10

2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Treatment of SEVERE Hypoglycemia in Unconscious Person with no IV Access Treat with 1 mg of glucagon subcutaneously or intramuscularly Call 911 Discuss with diabetes health-care team 11

Treatment of SEVERE Hypoglycemia in Unconscious Person with IV Access 2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Treatment of SEVERE Hypoglycemia in Unconscious Person with IV Access Treat with 10-25 g (20-50 mL of D50W) of glucose intravenously over 1-3 minutes Retest in 15 minutes to ensure the BG >4.0 mmol/L and retreat with a further 15 g of carbohydrate if needed Once conscious, eat usual snack or meal due at that time of day or a snack with 15 g carbohydrate plus protein 12

Treatment of SEVERE Hypoglycemia in Conscious Person 2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Treatment of SEVERE Hypoglycemia in Conscious Person Treat with oral “fast sugar” (simple carbohydrate) (20 g) to relieve symptoms Retest in 15 minutes to ensure the BG> 4.0 mmol/L and retreat with a further 15 g of carbohydrate if needed Eat usual snack or meal due at that time of day or a snack with 15 g carbohydrate plus protein 13

2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Recommendations 1-2 2018 All people with diabetes currently using or starting therapy with insulin or insulin secretagogues and their support persons should be counselled about the risk, prevention, recognition and treatment of hypoglycemia. Risk factors for severe hypoglycemia should be identified and addressed [Grade D, Consensus] The DHC team should review the person with diabetes’ experience with hypoglycemia at each visit including an estimate of cause, frequency, symptoms, recognition, severity and treatment, as well as the risk of driving with hypoglycemia [Grade D, Consensus] DHC, diabetes health-care team

2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Recommendation 3 2018 3. In people with diabetes at increased risk of hypoglycemia, the following strategies may be used to reduce the risk of hypoglycemia: Avoidance of  pharmacotherapies associated with increased risk of recurrent or severe hypoglycemia [Grade D, Consensus] (see Glycemic Management  in Adults with Type 1 Diabetes in Adults with Type 1 Diabetes; Pharmacologic Glycemic Management of Type 2 Diabetes in Adults, for further discussion of drug-induced hypoglycemia) A standardized education program targeting rigorous avoidance of hypoglycemia while maintaining overall glycemic control [Grade B, Level 2] Increased frequency of SMBG, including periodic assessment during sleeping hours [Grade D, Consensus] Less stringent glycemic targets with avoidance of hypoglycemia for up to 3 months [Grade D, Level 4] A psycho-behavioural intervention program (blood glucose awareness training) [Grade C, Level 3] Structured diabetes education and frequent follow-up [Grade C, Level 3 for type 1 diabetes; Grade D, Consensus for type 2] SMBG, self-monitoring of blood glucose

2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Recommendation 4 2018 In people with diabetes with recurrent, or severe hypoglycemia, or impaired awareness of hypoglycemia, the following strategies may be considered to reduce or eliminate the risk of severe hypoglycemia and to attempt to regain hypoglycemia awareness: Less stringent glycemic targets with avoidance of hypoglycemia for up to 3 months [Grade D, Level 4] CSII or CGM or sensor augmented pump with education and follow-up for type 1 diabetes [Grade B, Level 2] Islet Transplantation for type 1 diabetes [Grade C, Level 3] Pancreas transplantation for type 1 diabetes [Grade D, Level 4] CGM, continuous glucose monitoring; CSII, continuous subcutaneous insulin infusion

2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Recommendation 5 Mild to moderate hypoglycemia should be treated by the oral ingestion of 15 g carbohydrate, preferably as glucose or sucrose tablets or solution. These are preferable to orange juice and glucose gels [Grade B, Level 2]. People with diabetes should retest BG in 15 minutes and re-treat with another 15 g carbohydrate if the BG level remains <4.0 mmol/L [Grade D, Consensus] Note: This does not apply to children. See Type 1 Diabetes in Children and Adolescents; and Type 2 Diabetes in Children and Adolescents, for treatment options in children BG, blood glucose

2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Recommendation 6 6. Severe hypoglycemia in a conscious person with diabetes should be treated by oral ingestion of 20 g carbohydrate, preferably as glucose tablets or equivalent. BG should be retested in 15 minutes and then re-treated with another 15 g glucose if the BG level remains <4.0 mmol/L [Grade D, Consensus] BG, blood glucose

2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Recommendation 7 7. Severe hypoglycemia in an unconscious individual with diabetes With no intravenous access: 1 mg glucagon should be given subcutaneously or intramuscularly. Caregivers or support persons should call for emergency services and the episode should be discussed with the DHC team as soon as possible [Grade D, Consensus] With intravenous access: 10-25 g (20-50 mL of D50W) of glucose should be given intravenously over 1-3 minutes [Grade D, Consensus] DHC, diabetes health-care team

2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Recommendations 8-9 8. Once the hypoglycemia has been reversed, the person should have the usual meal or snack that is due at that time of the day to prevent repeated hypoglycemia. If a meal is >1 hour away, a snack (including 15 g carbohydrate and a protein source) should be consumed [Grade D, Consensus] 9. For individuals with diabetes at risk of severe hypoglycemia, support persons should be taught how to administer glucagon [Grade D, Consensus]

2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Key Messages It is important to prevent, recognize and treat hypoglycemic episodes secondary to the use of insulin or insulin secretagogues It is safer and more effective to prevent hypoglycemia than to treat it after it occurs, so people with diabetes who are at high risk for hypoglycemia should be identified and counselled about ways to prevent low blood glucose It is important to counsel individuals who are at risk of hypoglycemia and their support persons about the recognition and treatment of hypoglycemia

2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Key Messages The goals of treatment for hypoglycemia are to detect and treat a low BG level promptly by using an intervention that provides the fastest rise in blood glucose to a safe level, to eliminate the risk of injury and to relieve symptoms quickly. Once the hypoglycemia has been reversed, the person should have the usual meal or snack that is due at that time of the day to prevent repeated hypoglycemia. If a meal is >1 hour away, a snack (including 15 g carbohydrate and a protein source) should be consumed It is important to avoid overtreatment of hypoglycemia, since this can result in rebound hyperglycemia and weight gain BG, blood glucose

Key Messages for People with Diabetes 2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Key Messages for People with Diabetes Know the signs and symptoms of a low blood glucose level. Some of the more common symptoms of low blood glucose are trembling, sweating, anxiety, confusion, difficulty concentrating or nausea. Not all symptoms will be present and some individuals may have other or no symptoms Carry a source of fast acting carbohydrate with you at all times such as glucose tablets, lifesavers and/or a juice box

Key Messages for People with Diabetes 2018 Diabetes Canada CPG – Chapter 14. Hypoglycemia Key Messages for People with Diabetes Wear diabetes identification (i.e. a MedicAlert® bracelet) Talk with your diabetes health-care team about prevention and emergency treatment of a severe low blood glucose associated with confusion, loss of consciousness or seizure

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