How diabetes affects the body: outlining acute and chronic complications

Jos Selwyn-Gotha
April 2013

What happens if you have no insulin?Before 1922, and the work of Nobel Prize winning Canadian medics Dr Frederick Banting and Charles Best (still a medical student at the time), developing diabetes in childhood was akin to a death sentence. It was described by ancient physician Hippocrates as a short, disgusting and painful condition (Medvei, 1993) due to the rapid dehydration, starvation, pain, and coma leading to death that occurred in type 1 DM.Polyuria (massive urine production) occurs because the increasing amounts of glucose unregulated in the blood stream shifts the osmotic balance of the blood to the point that when the kidneys filter the blood, less of it is returned at the distal end of the nephron (the structure that filters blood in the kidneys). This means water, and important electrolytes, such as potassium and sodium, are being taken out of the system and no longer returned by the kidney, causing polydipsia (increased thirst), a sensation we feel at just 1% dehydration.Fortunately, glucose is also excreted along with the other products when it displays high blood levels, but not in significant enough quantities as to correct the problem. Characteristically, patients developing diabetes drink large quantities of water while urinating large quantities of sweet-smelling urine, frequently throughout the day and night. There is an inability to keep up with the vast amounts of water being excreted, which means a lack of insulin also leads to dehydration.Insulin is released when blood sugar levels rise after a meal. All excess glucose from carbohydrates that are unused by cells for energy are encouraged to be stored as glycogen by a process known as glycogenesis. This is stored as emergency reserves for the body to use in starvation, and release is stimulated by glucagon.The lack of insulin and subsequent high levels of glucagon lead to a breakdown of fat and muscle tissue glycogen, a large molecule containing hundreds of chains of fatty acids. The body believes that food is scarce and at risk of starvation. Glycogen’s fatty acids are released and converted in the liver. These fatty acids eventually yield FADH2, NADH and acetyl coenzyme A, which are used in the Krebs cycle of intra-cellular energy production. This process is used in cells to continue normal function from energy reserves or normal dietary intake. The brain exclusively uses glucose in normal life, not the products of stored energy breakdown as described above, which can lead to a faint feeling in starvation.However, unlike in normal function, ketone bodies are produced as a by-product of the fatty acid synthesis. This isn’t normally a problem because the body does not have to break down the carbohydrate glucose that is ideally available to use as energy. These ketone body by-products do have a use, as after a few days starvation they will begin to be taken up as an energy source by the brain and heart to keep a person alive. Until then they are excreted (Table 2).Table 2.Common ketones produced by the bodyKetones are acidic and can unbalance the pH of the blood.Ketones cannot be converted back into acetyl coenzyme A (acetyl-CoA) and therefore have to be metabolised or excreted within a few hours. This causes a continual process of breakdown in diabetes, even if there is minimal energy expenditure by the patient.Acetone is a by-product, along with CO2 of fatty acid breakdown. It is produced in small quantities in the liver and excreted in respiration and urination.Acetoacetic acid is released when ketones are being used in the production of energy for use in the brain in starvation.beta-Hydroxybutyric acid is used by the brain as an energy source in low-glucose states, and is a by-product of the production of the useful metabolic enzyme acetyl-CoA, which is used in cells as energy through Kreb’s Cycle.Ketone bodies are detected by using a nitroprusside dipstick, which turns from pink to purple in the presence of ketones.We can use the fact that ketone bodies are released specifically in the breakdown of fats to detect diabetes. One type of ketone body (acetone) is excreted by the kidney in this process, and is detectable in the urine as ‘ketouria’. A urinalysis positive for this will indicate a starved or diabetic state. Ketones are also excreted in respiration, so a sweet, fruity smell of acetone on a patient’s breath may also be present. Ketones may smell like nail polish remover, because that is one of the domestic uses of acetone.In the meantime, the normal blood glucose is not being taken into cells and used as energy because insulin isn’t encouraging its uptake. The cells are blind to the presence of glucose and instead use the synthesised fatty acids and ketone bodies to stay alive. The kidney will excrete glucose in detectable, high levels that can be seen in urinalysis, due to the osmotic imbalance discussed earlier. This is called glycosuria. Normally, the nephrons in the kidney reabsorb glucose as it filters blood in the proximal tubule, but at high levels it will be allowed to release through the urine, in an attempt to counter the osmotic imbalance that leads to polyuria.These previously described problems in diabetes are all unpleasant and distressing, but due to the acidic nature of ketones, the most acute problem becomes evident with a shift in the pH of blood. Blood needs to have a pH between 7.35–7.45 to be compatible in life, and this metabolic acidosis causes a series of symptoms that can quickly lead to death. This will be discussed in the next section.An undiagnosed diabetic can present acutely, more often in type 1 DM than type 2. Remembering that in type 1 diabetes insulin production may have halted completely, all the above processes are happening, which can appreciably lead to serious illness in a very short period of time. People with type 2 diabetes are not always as acutely affected by their insulin levels as they still have limited function, which is more likely to lead to less specific symptoms such as fatigue and headaches from excessively high blood glucose over a longer period of time, or may only be picked up during routine checkups without any symptoms presented at all.

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