The idea of type 2 diabetes (T2D) being a progressive illness is almost redundant, with increasing evidence even confirming how T2D remission is possible. For example, Cucuzzella et al (2023: 146) note that therapeutic carbohydrate restriction is an effective option in T2D management, improving the condition, reducing medication burden and achieving weight loss.
Accordingly, there has been a move away from medical practice that concentrates ‘almost exclusively on prescribing and intensifying medical therapy as chronic disease progresses’ and towards ‘safely de-prescribing medications’ (Cucuzzella et al, 2023).
As Johnson (2021) observes, T2D ‘is much more reversible than was once thought’ and since ‘[m]ost drugs are designed to combat hyperglycaemia, counteract the deficiency in glucose-stimulated insulin secretion, and increase insulin sensitivity in the context of frank diabetes’, it is arguable that substantial pathology has occurred before deranged glucose concentrations are detected, and that some drug-related approaches ‘may be double-edged swords.’
Concomitant with this change of emphasis is a shift of focus towards those elements whose accumulation help determine the diagnosis of T2D. One distinct feature on the T2D landscape is hyperinsulinaemia, an outcome of dysregulated insulin secretion and/or clearance resulting in chronically elevated concentrations of insulin and is common in obesity and metabolic disorders (Thomas et al, 2019). A widely posited model for the development of hyperinsulinaemia is one that begins with the onset of insulin resistance (IR), which occurs when glucose disposal in response to a particular concentration of insulin is impaired (Gallagher and LeRoith, 2020).
IR is a feature of obesity, especially abdominal obesity, but although obesity is typically defined by body mass index (BMI), ‘traditional BMI cut-offs are poor predictors of IR in certain populations, and there are metabolically unhealthy individuals with normal BMI’ (Gallagher and LeRoith, 2020).
The need for more research into factors leading to T2D is sharpened by the title of a paper by Zhang et al (2019) demonstrating that endogenous hyperinsulinaemia contributes to pancreatic cancer development. The authors explain that the continuing rise in the incidence of cancers – like pancreatic ductal adenocarcinoma – in line with global obesity and diabetes epidemics ‘suggests that factors modulated by environment or lifestyle play a key role, but the mechanisms by which obesity and type 2 diabetes promote cancer remain unclear’ (Zhang et al, 2019). However, in a more recent study, Zhang et al (2023) used a mouse model to test the hypothesis as to whether hyperinsulinemia in the obese state acts directly on acinar cells to promote pancreatic cancer initiation, and they found that their data ‘clearly support a model in which insulin receptors in acinar cells play a causal role in supporting cancer initiation.’
Given the close relationship between obesity, diabetes and cancer, Giovannucci (2022) explains that many novel cancer therapies are based on inhibition of various points in the insulin receptor signalling pathway, involving, for example, tyrosine kinase inhibitors, phosphatidylinositide-1 kinase inhibitors and protein kinase b inhibitors: ‘[b]y blocking insulin signalling, all of these can initiate or worsen IR. In fact, hyperglycaemia can be considered as a marker of effective blockade of this pathway.’
Looking to the future, Giovannucci (2022) anticipates a need to evaluate the respective roles of diet, lifestyle, and pharmaceuticals in relation to improving glycaemic and insulin control, ‘particularly in the context of cancer drugs that dysregulate the insulin signalling pathways.’
Given the inevitable pharmaceutical complexities that may accompany medication-mediated approaches to cancer treatment among those with IR, hyperinsulinaemia, T2D and associated conditions, a preventive approach that avoids the conditions leading to the carbohydrate intolerance resulting from poor nutrition in the first place seems reasonable. In this context, dietary strategies that reduce circulating concentrations of insulin seem appropriate … and straightforward. Noakes (2023: 45) notes that, although the human brain needs between 25 g and 100 g of carbohydrate daily, ‘the human liver can produce more than enough glucose to cover the brain’s glucose requirement without any need for ingested carbohydrate.’ With clear evidence that one of the contributing factors to the development of T2D – hyperinsulinaemia – can precipitate metabolic havoc, it is evident that, as Noakes (2023: 46) observes, a consequence of ‘basing a diet on a macronutrient that serves only one function … is that this carbohydrate-heavy diet will be deficient in key nutrients, which will produce negative health consequences.’
Current dietary guidelines that promote carbohydrate-heavy diets must change.