Statistics from Altmetric.com
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 HbA1c 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)?
The search was conducted independently by four reviewers. An advanced search of the electronic databases Medline (1946 to present) and PubMed Central using the search strings: (paediatric OR pediatric OR child OR infant) AND (Diabetes Mellitus OR T1DM OR Type 1 Diabetes Mellitus OR Type One Diabetes Mellitus) AND (ketogenic diet) and mapped to subject headings. The search was repeated excluding age restrictions to ensure capture of all relevant articles.
The initial search identified six articles. With limited results regarding the ketogenic diet the authors extended the search. The search strings were expanded to ‘AND (ketogenic diet OR low carbohydrate diet)’ to ensure patients with T1DM on low or restricted carbohydrate diets were included. The number of articles increased to 10. Full access was obtained for each.
Four articles (table 1) were case reports of children with T1DM and seizure disorders managed with ketogenic diets. Table 2 presents a case series by de Bock et al in Pediatric Diabetes 1, describing six children with T1DM started on low-carbohydrate diets, and a clinical report of 22 adult patients with T1DM on low-carbohydrate diets by Nielsen et al in Upsala Journal of Medical Science. 2 Two scientific review articles on ketogenic diets (Kanikarla-Marie and Jain, Free Radical Biology 3 and Medicine, and Mobbs et al, Journal of Child Neurology 4) and two review articles on low-carbohydrate diets (Arora and McFarlane, Nutrition and Metabolism,5 and Feinman et al, Nutrition 6) were also identified.
A search of the Cochrane Library Database using the same search terms identified no systemic reviews of the use of ketogenic/low-carbohydrate diets, only a Cochrane Review of low glycaemic index food consumption by patients with diabetes.7 This was excluded as beyond the scope of our question.
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 HbA1c 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 HbA1c 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 HbA1c ≤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 (HbA1c 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.
Clinical bottom line
Evidence shows that low-carbohydrate/ketogenic diets can reduce hyperglycaemia and improve HbA1c in adult and paediatric patients with type 1 diabetes mellitus (T1DM) in the short term. Despite this, low-carbohydrate/ketogenic diets should not be routinely recommended for paediatric patients with T1DM for the following reasons:
Low-carbohydrate diets in paediatric patients with T1DM have been shown to cause potentially serious endocrine, metabolic and psychological side effects. These are real clinical risks. It is therefore difficult to achieve ethical approval for prospective studies on the use of low-carbohydrate diets in children with T1DM. There are no systemic reviews, no cohort studies and no case–control studies of children with T1DM managed on a ketogenic diet. Our literature search identified four case reports and one case series. This corresponds to level 4 on the Oxford Centre for Evidence-Based Medicine Scale.15
There is no consensus regarding an acceptable level of ketosis for paediatric patients with T1DM on a ketogenic diet; making it challenging to discern diet-induced ketosis from early diabetic ketoacidosis.
There is not sufficient long-term evidence of children with T1DM managed on low-carbohydrate/ketogenic diets. Unpalatability and poor tolerance is common. Adherence is challenging and may become an increasing issue as children gain increased independence over their food choices.
The authors thank their patient and his parents for their kind permission to share his experience for educational purposes.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.