Recurrent hypoglycaemia with reduced recognition
Diabetes type 1
A 32-year-old man presents to his GP after a hypoglycaemic episode on a building site. His management is discussed.
People with diabetes may have an altered threshold to activate a sympathetic response and experience hypoglycaemic symptoms at a higher BGL than people without diabetes if their mean glucose is high. They may also develop symptoms when their BGL falls rapidly, even at higher absolute levels of glucose.2
Management of hypoglycaemia starts with prevention. In people whose work requires high-level physical activity, BGLs should be monitored and in a safe range (e.g. >5 mmol/L) before starting work. BGLs should be checked every two hours and maintained above 5 mmol/L during high-risk activities such as operating machinery or driving. Access to a hypoglycaemia kit (food/drink containing fast-acting carbohydrate and a glucagon pen) is vital. Family members and work colleagues can be trained to recognise hypoglycaemia and administer glucagon. Work should be ceased immediately and BGL checked at the first suspicion of hypoglycaemia, and action should be taken to treat mild hypoglycaemia as described in Box 3.
Kidney and liver dysfunction, which can impair insulin excretion or the counterregulatory response to hypoglycaemia, should be excluded. Autoimmune diseases associated with type 1 diabetes (coeliac disease, Addison’s disease, autoimmune thyroid disease) may also increase hypoglycaemia risk and screening should be considered. Ensure up-to-date screening for macro- and microvascular complications of diabetes, particularly retinopathy and peripheral and autonomic neuropathy, which may impact on workplace safety.
Intoxication impairs an individual’s ability to recognise hypoglycaemia and respond appropriately. People with diabetes should avoid excessive alcohol consumption and consume adequate carbohydrates before drinking.
Mark takes rapid-acting insulin with meals and long-acting insulin at night. He does not count carbohydrate serves, dose according to carbohydrate intake or use a specific formula to calculate correction doses. Although he occasionally checks his BGL before meals, he says he can usually feel when he is high or low and will adjust the insulin dose without doing a fingerprick test. He does not keep a written record of BGLs and did not bring his glucometer to today’s visit.
Mark reports a few episodes of diabetic ketoacidosis in his youth, but not in the past 10 years since becoming consistent with insulin injections. His last HbA1c level was 7.1% (54.1 mmol/mol). He has mild nonproliferative diabetic retinopathy and previous evidence of albuminuria, with normal estimated glomerular filtration rate.
Mark’s blood pressure is 135/80 mmHg, with no postural drop. His body mass index is 23 kg/m2. He has good sensation in his feet and intact pedal pulses. He has two firm lumps on either side of his umbilicus where he has been injecting insulin. Examination of other systems is unremarkable.
You advise Mark that you need more information to make a full assessment and allow him to return to work after two days, on the condition that he checks his BGL before and after every meal. You advise him not to drive or perform high-risk activities until further assessment. You refer Mark to a CDE, dietitian and endocrinologist and arrange to see him in a week’s time. You advise him to avoid injecting into the lumpy areas and to rotate his injection sites widely over the abdomen. You arrange for HbA1c, thyroid stimulating hormone and morning cortisol levels and coeliac serology to be tested.
Lipohypertrophy can be prevented by rotating injection sites and avoiding reuse of needles. Affected areas should not be injected until it resolves, which takes months to years. If unaffected areas are used, insulin requirements may decrease by up to 50%. Frequent BGL monitoring is advised.
Severe hypoglycaemia is defined as a hypoglycaemic event where the person is unable to treat themselves and requires the assistance of a third party. After an episode of severe hypoglycaemia, a person should not resume driving for a minimum of six weeks and until specialist approval, based on documented BGLs.
From the healthcare provider’s perspective, patients should be advised of their obligation to report changes in their fitness to drive to the DLA. A doctor may report directly to the DLA if the patient is unable to appreciate the impact of their condition and continues to drive against medical advice, possibly endangering public safety. The doctor is protected from liability, even if reporting is made without patient consent. In South Australia and the Northern Territory, reporting by the healthcare professional is mandatory if a patient is considered unfit to drive. It is the doctor’s duty to notify the relevant authority. It is preferable in all instances for patient consent to be obtained, and necessary for the doctor to inform the patient of their intention to report.
Further information is available in the Austroads Assessing fitness to drive document (https://www.onlinepublications.austroads.com.au/items/AP-G56-17).
Adequate awareness of hypoglycaemia may be restored by strict avoidance of hypoglycaemia for at least six weeks. This may necessitate resetting blood glucose targets to a higher range and tolerating a greater degree of hyperglycaemia for some weeks. Not all patients will regain full awareness.
Injection into the thigh and arm increases the risk of IM insulin injection because of the reduced depth of the subcutis. This risk is even higher in slim patients (up to 58% in men with a body mass index less than 25 kg/m2).4 Although the risk of IM insulin injection into the arm can be reduced with a lifted skin fold, it is extremely difficult to do properly by self-administration. Further, insulin may be absorbed too rapidly from these sites during exercise, as activity stimulates greater blood flow to these more vascularised areas.
Optimal needle length provides the most reliable insulin delivery into the subcutaneous space with the least discomfort. In Australia, pen and syringe needles vary from 4 mm to 12.7 mm and 8 mm to 13 mm, respectively. Needles less than 8 mm are now recommended, as shorter needles are safe and better tolerated with no compromise in glycaemic control and insulin delivery.5 In obese patients, 4 mm needles are also as efficacious and safe. If needles of 8 mm or longer are used, injection should be performed at a 45 degree angle to reduce risk of IM insulin injection.
Flexible insulin dosing consists of two components: the insulin-to-carbohydrate (IC) ratio and the insulin sensitivity factor. The IC ratio can be expressed as the amount of carbohydrate in grams that is covered by one unit of rapid-acting insulin, or alternatively, the number of insulin units required to cover for one serve (15 g) of carbohydrate. For example, a patient with an IC ratio of one unit per 15 g requires three units of insulin for three slices of bread (45 g). The insulin sensitivity or correction factor determines the amount of extra insulin needed to return a high BGL to normal after two to three hours. An insulin sensitivity factor of two means that one unit of insulin will lower the BGL by 2 mmol/L. Both the IC ratio and insulin sensitivity factor are generally determined after assessment by an endocrinologist.
Flexible insulin dosing requires accurate carbohydrate counting skills and regular premeal BGL checking. Patients should be referred to a dietitian and demonstrate competency in carbohydrate counting before commencement. There are several smart-phone applications that can help assess the amount of carbohydrate content in different foods, and ‘bolus advice meters’ into which the IC ratio and insulin sensitivity factor can be programmed, allowing the glucose meter to assist with insulin dose calculation.
He learns carbohydrate counting and sees an endocrinologist who recommends switching the dosing schedule to 2 units of rapid-acting insulin per carbohydrate serve, with a correction dose of one unit for every 2 mmol/L above a target of 7 mmol/L. He is advised to keep his BGL above 5 to 6 mmol/L for the next six weeks until his awareness of hypoglycaemia improves. He acquires a bolus advice meter to assist with mathematical calculation.
Mark returns after two weeks. He is still having some low blood glucose readings, particularly after unplanned extra physical activity at work. He has been monitoring his BGLs regularly, but complains that he feels ‘like a pincushion’ with the frequency of testing and it is troublesome to clean his hands for testing on the work site.
The FreeStyle Libre Flash Glucose Monitoring System (Abbott) comprises a sensor and a reader. The sensor is a small (35 mm x 5 mm) patch, applied on the back of the upper arm via a thin flexible sterile fibre. The sensor is designed to stay on the body for up to 14 days and is water resistant. The wearer scans the reader, of similar size to a glucometer, over the sensor, delivering the value of the interstitial glucose to the reader within a second, even through clothing. The reader displays current glucose values in real time, along with a graph of the past eight hours, and an arrow indicating if glucose is rising, falling or stable. It stores up to 90 days of downloadable glucose data.
A continuous glucose monitor (CGM) is a small wearable device which measures interstitial glucose every five minutes, notifying the wearer of current glucose level and recent glucose trend. Preset alarms are triggered when the glucose level goes beyond target range. Glucose readings are transmitted to a receiving device, such as an insulin pump or smart phone. There are several CGM systems available in Australia, including the Dexcom G5 and Medtronic Guardian Connect (which transmit data to a smart phone or other display device) and the Medtronic Minimed 640G.
These systems measure interstitial fluid glucose instead of capillary blood glucose, measured by traditional fingerprick testing. Interstitial fluid glucose lags about five to 10 minutes behind changes in BGL, but most of the time this lag is unlikely to affect day-to-day diabetes care decisions.7 Out-of-range readings should be verified by fingerprick before taking action.
Patients with recurrent severe hypoglycaemia and documented unawareness when BGL is below 3 mmol/L, despite optimisation of insulin therapy, can be considered for islet cell transplantation. Standard medical inclusion criteria are type 1 diabetes for five years or more, age above 18 years, creatinine clearance of more than 75 mL/min/1.73m2, serum creatinine level less than 130 mcmol/L, 24-hour urine protein estimation less than 300 mg/day, and weight ideally less than 80 kg.10 Islet transplantation can restore hypoglycaemic awareness in most patients for two years or more after transplantation, even if insulin independence is not maintained.11 Efficacy may wane over time and benefits must be weighed against the side effects of chronic immunosuppressive therapy.
Various pharmacotherapies such as beta-agonists, caffeine and theophylline derivatives, selective serotonin reuptake inhibitors and naloxone have been trialled with varying degrees of success in improving hypoglycaemic awareness, but further research is required before clinical implementation. Some practice points on management of patients with recurrent hypoglycaemia with reduced recognition are given in Box 4.
