Scenario

A 5-year-old boy with known type 1 diabetes mellitus (T1DM), treated with insulin, presents to the paediatric diabetes outpatient department for his routine clinic review. The family have started the boy on a ketogenic diet (<50 g of carbohydrates daily with target blood ketones of 2–3 mmol/L) to improve his diabetes control and for additional perceived health benefits. On the ketogenic diet, the patient’s insulin needs decreased, his HbA_1c is good (41mmol/L/5.2%) and his height and weight are increasing along the 75th centile for his age. He has normal screening bloods (including lipids) and a normal ECG.

The paediatric diabetes multidisciplinary team traditionally recommend a low-fat, high-carbohydrate diet for children with T1DM. The team have no experience of using a ketogenic or low-carbohydrate diet for the management of T1DM in children treated with insulin. You wonder if there is evidence to support the ketogenic diet in children with T1DM and if there are potential risks associated with the low-carbohydrate diet.

Structured clinical question

In children with type 1 diabetes mellitus treated with insulin (population), is a ketogenic diet (intervention) effective in improving glycaemic control or do the risks outweigh any potential benefits (outcomes)?

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Commentary

Nutritional management is a cornerstone of T1DM care. The International Society for Paediatric and Adolescent Diabetes (ISPAD)8 and the National Institute for Health and Care Excellence (NICE) recommend that 50%–55% of energy is derived from carbohydrate,<35% from fat and 15%–20% from protein.9 The ketogenic diet is very low in carbohydrate (<50 g) with compensatory increase in protein and fat. It provides the body with an alternative fuel source (ketones) through increased fatty acid oxidation.10

Improved glycaemic control for adult patients with diabetes managed with low-carbohydrate diets is recognised in the literature.^5-6. Improved HbA_1c was demonstrated by Nielsen et al who commenced 22 adult patients with T1DM on a carbohydrate-restricted diet (70–90 g carbohydrates per day) and reduced patients’ mean HbA_1c from 7.5% (58 mmol/mol) to 6.4% (46 mmol/mol).2

The impact of elevated ketone bodies is hotly debated in the literature. Kanikarla-Marie and Jain presented evidence from human, animal and cell culture studies to illustrate sustained ketosis leads to oxidative stress, vascular inflammation, hyperlipidaemia and liver dysfunction.3 Consequently, they recommended patients should not be exposed to high ketone levels.3 In contrast, Mobbs et al suggested that ketosis could reverse diabetic complications and presented their study of eight mice with T1DM and diabetic nephropathy. After 8 weeks on a ketogenic diet the mice’s nephropathy was reversed.4

The case reports of children with T1DM on ketogenic diets are presented in tables 1 and 2. Four children had severe neurological disease and ketogenic diets were started for epilepsy management after multiple medication failures.7 11–13 The other six children were otherwise healthy and commenced on low-carbohydrate diets by their parents.1

The recommended NICE target of HbA_1c ≤48 mmol/mol (6.5%) was achieved in seven children but authors reported frequent hypoglycaemic episodes.1 7 11–13 Distinguishing diabetic ketoacidosis (DKA) from diet-induced ketosis was challenging. Unpalatability was problematic, with 70% of children stopping the ketogenic diet due to limited food choices.^1,7-10. Reported side effects included low energy, hunger, poor sleep, amenorrhoea, delayed bone age and hypoglycaemia.1 The children had nutrient deficits and severely impaired growth.1 Four patients had elevated fasting cholesterol.14 Psychological ill health included low mood and obsessive behaviours.1

Case history, child and family perspective

The boy, in this case, was diagnosed with type 1 diabetes at age 5 years, not in DKA (HbA_1c 70 mmol/mol on diagnosis). The boy was started on a basal bolus insulin regimen and carbohydrate counting taught to the family immediately, with attendance at a structured diabetes education programme within 3 months of diagnosis. The family had a healthy diet, in keeping with NICE and ISPAD guidance, prior to starting the ketogenic diet.8 9 The family have always had a positive attitude to coping with the diagnosis of type 1 diabetes, including a positive therapeutic relationship with all members of the paediatric diabetes multidisciplinary team with whom they will often contact for advice and support. The boy is socially appropriate, is enjoying school and extracurricular activities and has a good network of friends. The boy was on Levemir 0.2 units/kg body weight/day (basal insulin) with Apidra (rapid insulin) 1 unit to 15 g of carbohydrates for all meals, and an insulin sensitivity factor of 1 unit to reduced blood sugars by 10 mmol prior to starting the ketogenic diet.

Initially, the parents, the boy and his older sibling all started the ketogenic diet. The family derive pleasure from food and cooking. The father thoroughly enjoys spending a few hours per day preparing family meals and snacks. The mother and the sibling came off the diet after 3 months as they found it restrictive and felt low in energy. The boy and his father have continued the ketogenic diet until now, almost 4 years later. The boy is happy with his packed lunches for school and parties and does not express any desire to change his diet. He has full attendance at school. The family are open to the idea that he may wish to return to a ‘normal’ diet at a later stage.

A typical day’s meals for this boy currently would be bacon and egg for breakfast, with a small amount of bread or almond flour pancakes (<5 g of carbohydrates). For lunch he might have vegetables with tuna, some mayonnaise and strawberries, or vegetables with cheese, ham, olives and a plum (<6 g of carbohydrates). Dinner could be cooked vegetables, and meat with mayonnaise, or cooked vegetables and chicken with chorizo and cream sauce with walnuts (<6 g of carbohydrates). Snacks during the day could include coconut flakes, olives, some grapes or almond flour pancakes with a homemade chocolate spread.

On the ketogenic diet, the boy is now on Tresiba 0.3 units/kg body weight/day with Apidra given as fixed doses equating to 0.25 units/kg body weight/day. There are no additional correction doses and no increased blood glucose-level testing. His height is slightly below the 75th centile and weight just above the 75th centile for a boy of his age.

The family are aware of the potential clinical risks with the ketogenic diet, including unrecognised ketoacidosis, lower levels of other nutrients such as calcium, reduced response to glucagon for severe hypoglycaemia management, cardiovascular risks and increased potential for family conflict when older.