Diabetes Mellitus

Now onto another disease of the endocrine system: Diabetes!

Please note: Just like everything else on this site, this post should not be taken as medical advice. If you actually have diabetes, or suspect you might, listen to your doctor first and foremost, not a random second-year undergrad on the Internet.

Understand differences between type 1 and type 2 diabetes mellitus

Diabetes, as you probably know, is a condition in which not enough insulin is produced. That isn't to say that no insulin is produced, just that not enough insulin is produced.

So what is insulin exactly? Insulin, produced by the β-cells of the pancreas, is released when glucose levels rise (usually following a meal). It increases glycolysis (glucose oxidation), glycogenesis (synthesis of glycogen from glucose) and lipogenesis (synthesis of fatty acids from glucose), as well as active uptake of glucose by cells other than liver cells. Insulin also increases glucose uptake in the liver, but in a roundabout fashion: glycogenesis decreases the concentration of glucose inside liver cells, so glucose can enter by going down a concentration gradient. All of these processes work to decrease plasma glucose so that the β-cells cease to be activated.

There is an opposing hormone called glucagon, which is produced by the α-cells of the pancreas. Glucagon stimulates glycogenolysis (breakdown of glycogen into glucose), gluconeogenesis (formation of glucose from other sources, such as amino acids and lipids) and ketogenesis (breakdown of fatty acids into ketones). Glucagon, however, is usually only produced when there is a substantial drop in blood glucose levels, such as after fasting for a while.

So anyway, back to diabetes. As I said, it's a condition in which inadequate insulin is produced. In Type 1 diabetes, β-cells are destroyed by autoimmune processes, and thus little or no insulin is produced by cells of the body. It is sometimes known as "juvenile onset diabetes" as most patients with the condition develop it early on in life. In type 2 diabetes, patients have normal or elevated levels of insulin, but the cells are insensitive to it for some reason. Most patients with type 2 diabetes develop it in adulthood, but it can also occur in children. Both types may have underlying genetic components.

So what's so bad about not having enough insulin? Well, without insulin, blood glucose levels are higher than normal. This causes more glucose to be secreted into the urine. As water follows by osmosis, more urine is produced (polyuria). To make up for the water deficit, diabetic patients often have to drink a lot (polydipsia). Fun fact: diabetes mellitus is Greek for "sweet flow," referring to the sweet taste of urine. (Yup, before we had better tools, doctors actually had to taste their patients' urine to test for diabetes. Good thing we've moved beyond that!) Patients may also be hungry (polyphasia) as less glucose is entering their cells.

Type 1 and Type 2 diabetes have different treatments. In Type 1, since the symptoms result from a complete lack of insulin, the solution is to provide exogenous insulin. As I'm sure you're aware, many patients give themselves insulin via subcutaneous injection, but there are also continuous infusion pumps as well. Glucose levels also have to be monitored so that they know how much insulin to take etc. Unfortunately there is no known cure for type 1 diabetes.

Type 2 diabetes, on the other hand, seems to be more of a result of lifestyle factors such as poor diet and exercise (though the mechanism is not yet well understood), and thus these areas are targeted in treatment. A diet for a type 2 diabetic may include a lot of complex carbohydrates, fibre and protein, in order to reduce the demand for insulin. Exercise also increases uptake of glucose by skeletal muscles so that there's less in the circulation.

Oral hypoglycaemic drugs, which reduce glucose levels, may also help type 2 diabetics. These include sulfonylureas, which stimulate the β-cells of the pancreas to release insulin; biguanides, which increase sensitivity to insulin and reduce glucose production and absorption; and α-glucosidase inhibitors, which reduce glucose absorption by inhibiting digestion of disaccharides to monosaccharides.

Bariatric surgery can also help some type 2 diabetics, partly because it helps in losing weight, and even a 5% weight loss can help to normalise glucose levels. Sometimes, diabetes can resolve following bariatric surgery even before any weight loss occurs!

Understand how to differentiate between insulin shock and ketoacidosis in the unconscious diabetic

Insulin shock and ketoacidosis are two acute complications of diabetes. Insulin shock is caused by too much insulin, whereas ketoacidosis is caused by too little insulin.

Insulin shock is caused by too much insulin for the situation. For example, a type 1 diabetic may take insulin and then not eat, or exercise excessively, or throw up. This results in too much insulin for the amount of glucose actually circulating in the blood, and in turn results in lowered blood glucose levels within only a few hours. This depresses the central nervous system (CNS) as neurons need glucose to function, resulting in symptoms such as inability to concentrate, slurred speech, lack of coordination and staggering- all of which may be mistaken for alcohol intoxication. In order to try and compensate, the sympathetic nervous system (SNS) is activated to suppress insulin in an attempt to restore glucose levels, but this may not be sufficient. SNS activation results in other lovely symptoms like sweating, tachycardia (elevated heart rate), pallor (pale skin due to vasoconstriction), tremors and anxiety.

So how can insulin shock be treated? Treatment is relatively straightforward, and mainly consists of raising blood glucose levels. If the patient is conscious, they can eat or drink something sugary, like fruit juice or sugar. If the patient is unconscious they should not be given anything by mouth, but they can be given glucose intravenously.

Diabetic ketoacidosis has the opposite cause: inadequate insulin over the course of several days. Aside from forgetting to take insulin, this complication may develop due to infection, stress or binging on food or alcohol. In contrast to insulin shock, diabetic ketoacidosis is characterised by hyperglycaemia rather than hypoglycaemia. Also, since the glucose isn't getting into the cells, lipids may be broken down to provide energy, resulting in the formation of acidic ketones (hence "ketoacdosis").

Ketoacidosis has some of the symptoms of hyperglycaemia experienced by untreated diabetics: lots of sugary urine is formed, which leads to dehydration, which in turn leads to thirst, warm dry skin, low blood pressure and also oligouria (reduced urine production). There are also symptoms relating to acidosis, such as rapid respirations (gotta try and blow off that CO₂), fruity breath (the ketones have a fruity smell) and lethargy. Finally there are symptoms related to electrolyte imbalance, such as abdominal cramping, vomiting and lethargy.

Since ketoacidosis is caused by a lack of insulin, the treatment here is to administer insulin. The other symptoms should also be taken care of: the patient should be rehydrated, have their electrolytes replaced and acidosis treated with bicarbonate.

Now how do you tell the difference? That's pretty important- you don't want to be giving glucose to someone who has too much glucose or insulin to someone who has too much insulin. One giveaway sign is fruity breath, as this is only present in ketoacidosis. Ketoacidosis also has several signs of dehydration, which aren't necessarily shared by patients with insulin shock. I am a bit shaky on this one so I don't want to say any more- even though I've explicitly stated that this post is not medical advice, I'd hate it if I said the wrong thing and someone tried to force their friend suffering from ketoacidosis to drink a shitload of orange juice.

Appreciate the causes and clinical significance of chronic complications

Aside from acute complications, diabetes also has an array of chronic complications, which are thought to be the result in metabolism changes due to inadequate insulin. Type 1 diabetics are more likely to experience these as they obviously spend more time living with the disease. Diabetics are at greater risk of heart disease, stroke, blindness, neural impairment, kidney disease, non-traumatic amputations and pregnancy complications. Not a great list.

As our cardiovascular lecturer stated, "diabetes is one of the enemies of the blood vessels." He wasn't kidding. Macrovascular (large vessels) complications include increased risk of heart attack and stroke, as well as poor circulation to the extremities (hands and feet). This results in poor healing and a greater likelihood of infection, which is why so many non-traumatic amputations are in diabetic patients (my grandmother was unfortunately one of them).

Aside from the large blood vessels, diabetes can also affect the smaller vessels. Capillaries supplying the retina can become thick and hard, which make them more likely to rupture, resulting in blindness. Sorbitol can also accumulate in the lens, resulting in cataracts. Vessels supplying the kidneys can likewise become damaged: the glomerular basement membrane can thicken, leading to increased permeability and an increased risk of kidney failure.

Neural complications (neuropathy) are a little bit more of a mystery. Symptoms experienced here are numbness and tingling, if peripheral nerves are affected, or incontinence and erectile dysfunction, if autonomic nerves are affected. The cause of diabetic neuropathy is a little more uncertain and may related to vascular problems, autoimmune problems, demyelination or something else.