Treatment of diabetes mellitus 1041 Type 1 diabetes

In Type 1 diabetes, the only satisfactory treatment is to replace the missing insulin. However, this simple statement is not easy to put into practice. First, we must find some insulin. Until the last two decades, all insulin used by people with diabetes was extracted from the pancreas of cows and pigs. This had two disadvantages. The supply was finite and there were worries that it would never be sufficient to meet the needs of diabetic patients worldwide. In addition, both bovine and porcine insulin differ slightly from human insulin in amino acid sequence, and also the extracts were not completely pure; and these two factors together led to the development of insulin antibodies in people treated with these preparations - i.e. antibodies made against what the body sees as a foreign protein. In people who reacted particularly strongly in this way, the concentration of insulin antibodies became so high (binding the insulin that was given) that enormous doses of insulin had to be used; in fact, this was the original condition known as insulin resistance. Now, a protein identical with human insulin is produced by bacteria in culture, using recombinant DNA techniques; the supply is effectively infinite, the preparations are pure and the protein does not cause antibodies.

Even with a suitable insulin preparation, however, it has to be given to the subject. It cannot be swallowed because, like any other protein, it is broken down into its constituent amino acids before absorption from the intestine. Therefore it has to be injected. Nobody actually likes having an injection, and the number of injections given per day should ideally be as few as possible. But a major theme of this book has been the way in which metabolism is regulated by constantly changing, subtle alterations in the secretion of insulin. How can this possibly be mimicked by two or three injections each day? In addition, the anatomical relationship of the liver and the pancreas have been stressed in this book: insulin is secreted into the portal vein and exerts its initial effects on the liver. We cannot inject into the portal vein, and insulin is usually given into the subcutaneous adipose tissue (Fig. 10.6). How different will metabolic regulation be if insulin reaches the peripheral circulation in concentrations which can only change slowly, and which do not respond directly to changes in the concentration of glucose in the blood? The answer is that, with a suitable combination of injections three times a day, surprisingly normal glucose concentrations can be maintained in the blood: but never completely normal.

One important reason for the lack of complete normalisation is the balancing act which a person with Type 1 diabetes must perform between too little and too much insulin. Too little and the blood glucose concentration rises unduly and ketoacidosis begins; too much and the blood glucose concentration will fall below normal levels. This can happen very quickly, particularly if, for instance, the subject unexpectedly has to miss a meal or to take some exercise, having injected his or her normal amount of insulin. If the blood glucose con-

Fig. 10.6 Plasma insulin concentrations in non-diabetic subjects and people with Type 1 diabetes having three injections of insulin during the day. Based on Alberti, K.G.M.M., Boucher, B.J., Hitman, G.A. & Taylor, R. (1990) Diabetes mellitus. In: The Metabolic and Molecular Basis of Acquired Disease Vol. 1 (eds Cohen, R.D., Lewis, B., Alberti, K.G.M.M. & Denman, A.M.), 765 -840. With permission of the publisher W.B. Saunders.

Fig. 10.6 Plasma insulin concentrations in non-diabetic subjects and people with Type 1 diabetes having three injections of insulin during the day. Based on Alberti, K.G.M.M., Boucher, B.J., Hitman, G.A. & Taylor, R. (1990) Diabetes mellitus. In: The Metabolic and Molecular Basis of Acquired Disease Vol. 1 (eds Cohen, R.D., Lewis, B., Alberti, K.G.M.M. & Denman, A.M.), 765 -840. With permission of the publisher W.B. Saunders.

centration falls below about 2 mmol/l, then (as discussed in Section 4.2) the brain will suffer from a lack of substrate and changes in mood - e.g. irritability, slurred speech - will follow; if the glucose falls further, unconsciousness may occur. This is the condition of hypoglycaemia, or, if it leads to unconsciousness, hypoglycaemic coma. Because this condition can develop so rapidly, and because its consequences can be so severe, many people with diabetes tend to keep their plasma glucose concentration on the higher side of normal rather than the lower side. For many people nowadays, the process of checking their treatment has been made enormously simpler by the availability of portable devices to measure the glucose concentration in a drop of blood from a finger-prick.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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