Time after glucose (min) Fig. 10.2.1 Redrawn from Felber et al. (1993).
acids in blood as it is to measure glucose, we would think of diabetes mellitus mainly as a disorder of fat metabolism. Lack of insulin leads to unrestrained release of non-esterified fatty acids from adipose tissue, and also to lack of activation of adipose tissue lipoprotein lipase. Thus, adipocytes fail to take up triacylglycerol from the blood, and there is a dramatic net loss of fat from adipose depots. This, together with the breakdown of protein, leads to the catabolic state and rapidly developing wasted appearance of sufferers who do not receive treatment (see Fig. 10.1).
The concentration of non-esterified fatty acids in the plasma in untreated diabetes mellitus (normally in the range 0.2-1.0 mmol/l in healthy subjects) may reach 3-4 mmol/l. These high concentrations of non-esterified fatty acids, together with the lack of insulin (and possibly increase in glucagon) lead to increased fatty acid oxidation and ketone body production in the liver (see Fig. 10.3). The combined concentration of the ketone bodies 3-hydroxy-butyrate and acetoacetate in the blood is normally less than 0.2 mmol/l. In untreated diabetes, their combined concentration may reach 10-20 mmol/l. Remember that the ketone bodies are produced as the corresponding acids, 3-hydroxybutyric acid and acetoacetic acid. Thus, the level of acidity of the blood also increases - i.e. the pH falls, from the normal value of about 7.4 to perhaps around 7.1. This is a dangerous situation, known as diabetic ketoacidosis.
In addition, excess non-esterified fatty acids may be diverted into esterifica-tion in the liver despite the lack of insulin, and increased VLDL-triacylglycerol secretion may result. Triacylglycerol clearance from the plasma is much reduced because of lack of activation of adipose tissue lipoprotein lipase (Fig. 10.3). Thus, hypertriglyceridaemia is another feature of untreated diabetes mellitus.
The accumulation of substances such as ketone bodies and glucose in the blood, together with dehydration, leads to an increase in the osmolality of the blood. This, in combination with the increased acidity in the blood, causes changes in brain function which may lead eventually to unconsciousness - diabetic coma, or hyperglycaemic coma. This will progress to death if not treated. This was the fate of sufferers from Type 1 diabetes before the introduction of insulin treatment. Treatment of diabetic ketoacidosis consists of insulin together with fluid. Deaths from diabetic ketoacidosis are now, fortunately, rare.
The tendency to develop ketoacidosis is one feature that distinguishes Type 1 from Type 2 diabetes clinically. Those with Type 2 diabetes are generally more resistant to development of ketosis, presumably because the small amount of insulin secretion that remains is sufficient to prevent excessive ke-tone body formation. However, ketosis may occur when there is an additional metabolic stress such as infection.
Was this article helpful?
All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.