Type 1 Diabetes and Starvation

By Chandan Sekhon - Medicine Student @ Peterhouse, Cambridge

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Diabetes Mellitus is a collection of diseases where the blood glucose levels of an organism aren’t being maintained within an acceptable range. Insulin is the primary hormone responsible for maintaining blood glucose levels, although there are other messengers such as glucagon. Type 1 diabetes is an autoimmune disease where the immune system of an organism destroys beta cells, which are in islets of Langerhans in the pancreas. starvation can be defined as suffering or possible death due to a lack of food. Despite the difference between type 1 diabetes mellitus (T1DM) and starvation, the symptoms of T1DM can very closely resemble the effects of starvation if T1DM is left untreated.

In T1DM, the immune system of an organism recognises beta cells as ‘non-self’. This triggers an immune response where macrophages and other immune cells infiltrate the islets of Langerhans and destroy insulin-secreting beta cells. There is a genetic predisposition to T1DM – the inheritance of particular alleles can massively increase the risk of developing T1DM, so if someone’s parents or grandparents have T1DM, the chances of their offspring developing the disease are increased. There may also be an environmental trigger since some people develop the disease later in life (despite the disease mostly affecting younger age groups), although this potential trigger is currently unknown. Other risk factors for T1DM includes viruses. For example, children exposed to rubella as a foetus have an increased incidence of T1DM. Even the method of birth has been noted to have some effect on the incidence of the disease. This has been suggested due to the increased risk of developing the disease in children born by caesarean section.

T1DM can be compared to starvation in that the effects of starvation are very similar to the effects T1DM can have if left untreated. An individual can look like they are starving even when they aren’t – this is because there is no glucose uptake into skeletal and adipose tissues as it is all excreted. For both starvation and T1DM, the body recognises that there are very low intracellular glucose levels. This has multiple effects. The primary response will be glycogenolysis where glycogen molecules are hydrolysed to form glucose molecules, which the body uses as a temporary store of nutrients during both T1DM and starvation.

This cannot last long though, as glycogen stores are quickly depleted. During this time, other processes like gluconeogenesis can occur. Once these stored are completely utilised, the body turns to fats as the main energy source. Skeletal muscle predominately uses fats as its main source of energy at this stage, to allow the brain to use up any remaining glucose in cells since neuropathy (nerve damage) can result if the brain doesn’t obtain glucose. This is also a long-term result from T1DM and starvation.

In both cases, ketoacidosis takes place. This is where fatty acids are metabolized into ketone bodies to act as an energy store in the absence of glucose. Once these reserves are exhausted, the body switches to using proteins as the main energy source. Since muscles are the largest protein reserves in the body, these are decomposed first. Once this store is depleted; other, non-essential proteins, are broken down which leads to a reduction in cell function. Once all options are spent, the person will die. This is similar for both T1DM and starvation. Another similarity between the two is that for both states, there is a very low level of insulin, or in the case of T1DM, there is no insulin in the blood at all. For T1DM, no insulin is secreted, and in starvation, more glucagon is secreted to increase the blood glucose level.

Further reading:

1. A fantastic article giving an introduction to diabetes, which goes into some depth about the processes involved in the disease: https://www.ncbi.nlm.nih.gov/books/NBK1671/

2. More clinical article with signs, symptoms, causes and treatments for the disease: https://pharmaceutical-journal.com/article/ld/type-1-diabetes-pathophysiology-and-diagnosis

3. Interesting study about the effect of ethnicity on T1DM, its progression and prevalence: https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/485151

4. Article about the physiology of starvation. Quite detailed and challenging but an interesting read: https://www.sciencedirect.com/science/article/pii/S0899900706001766?casa_token=nRvtFG88weQAAAAA:118WUwOkFbQwDwqgESIrPhtjzC2Nvpjm-pwuYmyFwS4kclSpU3VM9e7Hg0yEzTbFcSw2LJld15M