This is the third article in my series on the Human Energy Metabolism.
If you are interested, the first two articles can be found here:

• Part #1 - Organ-specific Requirements
• Part #2 - The Respiratory Quotient

From now on we will turn toward quite specific issues of nutritional biochemistry. With this article I will provide a quick discussion of Diabetes mellitus - a metabolic disease that everyone has heard of, but which is still not perfectly understood.

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Aspects of nutritional Biochemistry I

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Image Source

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Diabetes mellitus

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In this disease, the hormon insulin is either not produced in sufficient amounts or target tissues do not respond properly. The consequence is, that blood glucose levels rise to abnormal levels, which leads to a "spill over" into the urine, providing a useful diagnostic criterion for the detection of the disease. This phenomenon is also known as "honey-sweet flow".

Despite the high levels of glucose in the blood, glucose needy cells „starve“ due to the absence of a functioning insulin-stimulated entry process. Cells respond by increasing triacylglycerol hydrolysis, fatty acid oxidation, gluconeogenesis and ketone body formation (ketosis).

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Under these circumstances keton bodies reach abnormally high levels in the blood and, as they are acids, this leads to an increased excretion of H+, Na+, K+, phosphate and water by the kidney. This in turn causes dehydration of the body and a decrease in blood volume. Hence excessive thirst is a classical symptom of Diabetes!

Furthermore, the formed ketone bodies formed can be discharged via the breathing air. This may also be used for diagnostics. E.g. acetone in the air can be detected both by special measuring devices as well as by trained diabetics-warning dogs. This allows an early detection and prevention of an upcoming hypoglycemic crisis!

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Insulin-dependent Type I Diabetes mellitus

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Type I Diabetes results from a lack of insulin due to deficient production in pancreatic β-cells which have been destroyed by an autoimmune attack. The disease emerges when more than 80 % of the β-cells have been destroyed.

Type I Diabetes develops during childhood and patients are required to maintain a strict diet accompanied by regular insulin doses. Despite this treatment patients have a 30 % reduced life span. This results from degenerative complications such as kidney malfunction as well as nerve and cardiovascular impairments.

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Non-insulin-dependent Type II Diabetes mellitus

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Type II Diabetes accounts for > 90 % of all cases with stunning 18 % of the population over 65 years of age being affected. Type II Diabetes preferentially occurs in obese individuals. Those patients have normal or even higher blood insulin levels. This type of diabetes arises from a paucity of insulin receptors on usually insulin-responsive cells. As a consequence, these cells do not respond normally to insulin and they are said to be „insulin-resistant“.

Again, blood glucose levels are elevated, particularly after a meal. Although some forms of type II diabetes (ca. 5 %) appear to be related to mutations in the insulin binding receptor, overeating and the consequential suppression of insulin receptor synthesis appear to be a major factor in the development of the disease. This hypothesis accounts for the observation that diet alone often decreases the severity of the disease - a certainly remarkable fact.

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The role of Insulin

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Insulin binds to the extracellularly located α-subunits of the dimeric, transmembrane insuline receptors. Upon insulin binding, the intracellular tyrosine kinase domain undergoes a conformational change leading to autophosphorylation. This in turn increases the tyrosine kinase activity. Insulin receptor substrate-1 (short IRS-1) binds to the receptor, is phosphorylated and activates other signalling pathways: gene activations, MAP kinases, RAS, etc.
This clearly shows the central role and thus importance of the insulin hormone for the proper function of our energy metabolism.

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Primary structure of human insuline - Image Source

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Facts and Statistics on Diabetes mellitus

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• Worldwide, over 400 million people are affected by some form of diabetes.
• In Central Europe, the number of diabetics has increased by 40 % since 1998.
• Diabetes may lead to blindness, kidney failure, heart attacks, strokes and the need for lower limb amputations.
• Kidney failure due to diabetes is responsible for a massive 26 % of all new dialysis patients.
• In a developed country like Austria, 62 % of the necessary amputations are due to diabetes.
• Since the disease is spreading, the WHO estimates that diabetes will be the seventh leading cause of death in 2030!
• A healthy diet, regular and sufficient physical activity as well as the maintenance of a normal body weight are promising ways to delay or even totally prevent the onset of type II diabetes.

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I hope you learned something new and interesting from this article! Since I will continue with this series, dealing with Starvation and Fasting in the next article, I hope you all will stay tuned for more. :)

Best,
mountain.phil28

References:

1. A article about diabetics-warning dogs
2. Statistics on Diabetes mellitus in Austria
3. Worldwide Statistics on Diabetes mellitus
4. Various Wikipedia Articles as referenced in the text
5. Further information and non-direct cited images are taken from "Biochemistry I" lectures at the TU Graz.