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The hormonal control of blood glucose and the management of diabetes

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The liver and the pancreas have a central role in the regulation of blood glucose concentration. The cells in the pancreas secrete the hormones which tell cells to take up glucose from the blood or not take it up. On demand, glucose is made from broken down glycogen in the liver.



The pancreas has alpha and beta cells. Alpha cells secrete glucagon which increases blood glucose concentration, while beta cells secrete insulin which decreases blood glucose concentration. People with type 1 diabetes have destroyed beta cells, so their lack of insulin makes them have to take it via injections.



The islets of Langerhans contain the hormone-secreting endocrine cells including the alpha and beta cells. Most of them are the insulin-producing beta cells, with a smaller proportion of alpha cells.


Blood glucose is too high


The pancreas detects this, so it secretes insulin. This stimulates the uptake of glucose from the blood by cells, and the storage of it in the liver once it’s converted to glycogen. This reaction is called glycogenesis. The stages are:


1. Insulin attaches to receptors on target cells

2. This triggers a change in how many channel proteins are included in the cell membrane

3. Separately, it also stimulates the activation of enzymes involved in converting glucose into glycogen


Blood glucose is too low


The pancreas detects this too, so it secretes its masterfully antidote: glucagon. This inhibits cells from taking up any more glucose from the blood, while initiating the breakdown of glycogen in the liver to produce more glucose. The glycogen is hydrolised (broken down in the presence of water) so the term for this reaction is glycogenolysis.


1. Glucagon attaches to receptors on target cells

2. This activates enzymes responsible for the conversion of glycogen into glucose

3. This activates enzymes responsible for the conversion of glycerol and amino acids into glucose



Another hormone involved in glucose regulation is adrenaline. This is secreted by the adrenal glands in times of stress or exercise. It has the same effect as glucagon. Both of these hormones act via a second messenger. That is, they bind to the plasma membrane of cells and exert their influence from the outside by causing a cascade of enzymatic reaction events inside the cell which ultimately end up in their response. They chicken out of it, don’t blame the messenger.


The second messenger model includes adenylate cyclase, cyclic AMP (cAMP) and protein kinase.



Thus glucagon (the first messenger) does not effect direct change, but acts via the second messenger pathway. Upon activation, the protein kinase adds phosphate groups to other proteins such as other enzymes. This activates them and can change other features such as their association with other proteins.




Type 1 diabetes is an auto-immune disease that develops early in life. The body destroys the pancreas islet cells responsible for the production of insulin. It is rectified with insulin injections and close monitoring of blood glucose. Advances are being made in recreating the missing cells either by transplantation, stem cell therapy or an implantable artificial device.



The causes of type 1 diabetes include genetic predispositions accounted for by more than 50 different genes, as well as environmental factors. This was discovered through studies of genetically identical twins who did not always both develop the disease. Environmental factors that may play a role include viral infections and exposure to certain drugs or chemicals in food e.g. certain proteins in gluten. The interplay between some or all of these genetic and environmental risk factors causes the condition.


Diagnosis of type 1 diabetes is done by blood glucose tests such as fasted blood glucose and glucose tolerance tests which indicate hyperglycaemia (high blood sugar), usually prompted by symptoms such as increased urination (polyuria), thirst (polydipsia) and hunger (polyphagia).


Unlike type 1, type 2 diabetes involves a desensitisation to insulin rather than its complete absence. It is associated with obesity and certain other health problems. The causes of type 2 diabetes are obesity and lack of exercise, and it constitutes a metabolic disorder.



While both genetic and environmental factors play a role, some can be helped while others cannot. Risk factors that cannot be helped include advanced age and genetic predisposition. Genetic predisposition is associated with certain population subgroups such as South Asian, African-Caribbean and Black African.


Diagnosis is made using a combination of blood tests and symptoms present. For example, a single high reading of fasting blood glucose with symptoms such as increased thirst or unexplained weight loss would provide the type 2 diabetes diagnosis, or two separate high readings of fasting blood glucose with no symptoms, or other combinations.



Other blood tests include the glycosylated haemoglobin test (HbA1c) and the glucose tolerance test. The glucose tolerance test involves ingesting a set amount of glucose e.g. 50 grams, and measuring the blood glucose level before and 2 hours later in order to see how quickly the glucose is being removed from the blood.


HbA1c is used to measure the 3-month glucose blood level, as the lifespan of a red blood cell is up to 4 months. This makes this test suitable for assessing a longer-term average of blood glucose levels compared to individual blood glucose measurements that only reflect the blood glucose level at that specific moment.


Treatment consists of an improved lifestyle with a better diet and more exercise. If it gets bad, insulin may be needed to supplement the patients’ own insulin.


Monitoring blood glucose is necessary in type 1 diabetes and may also be necessary in type 2 diabetes. Biosensors for glucose are used in strips to assess glucose levels from drawn finger prick samples. These can be carried out as needed by the patient themselves.


Immobilised enzymes are central to various diagnostic reagent strip such as blood glucose monitoring.



In glucose testing strips, the enzyme glucose oxidase is used to catalyse the first reaction of glucose. Further reactions of its byproducts can be used to create a colour change. This is then processed digitally to produce a reading on a screen.


Healthy blood glucose is in the range of 4.0 – 7.8 mmol / L based on fasting (up to 5.9 mmol / L) or 2 hours post-eating (below 7.8 mmol / L). For diabetics, the upper range goes up to 8.5 mmol / L (type 2) or 9 mmol / L (type 1).



Data can be saved manually or automatically so that the progress of maintaining blood glucose levels within healthy range can be tracked.


For type 2 diabetes, drugs can also be used to control the disease in addition to insulin itself. Metformin helps reduce mortality, while other drugs such as rosiglitazone may help with blood sugar levels. However, the long-term benefit of these drugs has not been established.


Diabetes healthcare and outlook


A cohort of healthcare professionals are required to manage the symptoms of patients and help prevent various other associated diseases. This includes diabetes specialist nurses, dieticians, retinal screeners and podiatrists.


Nurses help patients learn about diabetes and how to manage it best by themselves, as well as acting as a bridge between other professionals such as GPs (general practitioners) and endocrinologists. Dieticians help patients create and maintain a better diet, suitable for diabetes, that is rich in essential nutrients and can be realistically kept up by the patient on an individual basis.


Retinal screeners look for changes in the eye of diabetics in order to prevent the complications arising from long-term diabetes, such as diabetic retinopathy. Diabetes can affect the blood vessels in the eye, potentially incurring damage to the retina and causing loss of sight if left untreated. If the damage is caused in the central part of the retina i.e. the macula, the conditions is called diabetic maculopathy.


The NHS provides eye tests for diabetics and recommends tests are carried out yearly.


Since diabetes can harm blood vessels in the extremities such as the feet, it is important to maintain good foot health through a podiatrist. This is to avoid nerve damage i.e. peripheral neuropathy, as well as poor circulation which may damage the feet and render them prone to infections.



If injuries such as blisters are not healing quickly, podiatrists as well as GPs can provide adequate treatment. Self-care strategies for feet include maintaining them clean, wearing good, comfortable shoes and avoiding walking barefoot on the ground.



Diabetes worldwide is increasing sharply as increasing populations are living in urban areas and have access to more food high in sugar and fat. An estimate worked out in 2004 for how many people with diabetes would be in the world by 2030 was 366 million. In fact, 422 million people had diabetes much earlier, in 2016.



Another projection for 2030 (552 million) may still be exceeded. The highest burden of diabetes is expected to develop in Africa and Asia by that year. The areas where diabetes is becoming an issue the fastest are not necessarily the areas where the best healthcare is available to deal with this disease. The United States is a country with a high prevalence of diabetes (almost all cases are type 2), but also with a good level of healthcare to address it. In 2012, it spent $245 billion ($245,000,000,000) on diabetes. A chunk of this phenomenal figure is attributed to “lost productivity” due to diabetes.



In addition to this, a shortage of healthcare professionals such as the previously mentioned diabetes specialist nurses will create more challenges in providing proper treatment. Shortages arise as a result of an ageing population in certain developed parts of the world, as well as the rapid increase in the number of people suffering from diabetes.


As more people turn to an urban lifestyle, levels of physical exercise and physical labour decrease, while high-energy foods that are low in nutrients become a more appealing diet option i.e. the Western-style diet.


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