Diabetes Complications

Diabetic ketoacidosis
Diabetic ketoacidosis (DKA) is an acute and dangerous complication that is always a medical emergency. Low insulin levels cause the liver to turn to fat for fuel (ie, ketosis); ketone bodies are intermediate substrates in that metabolic sequence. This is normal when periodic, but can become a serious problem if sustained. Elevated levels of ketone bodies in the blood decrease the blood's pH, leading to DKA. On presentation at hospital, the patient in DKA is typically dehydrated, and breathing rapidly and deeply. Abdominal pain is common and may be severe. The level of consciousness is typically normal until late in the process, when lethargy may progress to coma.

Ketoacidosis can easily become severe enough to cause hypotension, shock, and death. Urine analysis will reveal significant levels of ketone bodies (which have exceeded their renal threshold blood levels to appear in the urine, often before other overt symptoms). Prompt, proper treatment usually results in full recovery, though death can result from inadequate or delayed treatment, or from complications (dg, brain edema). DKA is always a medical emergency and requires medical attention. Ketoacidosis is much more common in type 1 diabetes than type 2.

Nonketotic hyperosmolar coma
Hyperosmolar nonketotic state (HNS) is an acute complication sharing many symptoms with DKA, but an entirely different origin and different treatment. A person with very high (usually considered to be above 300 mg/dl (16 mmol/l)) blood glucose levels, water is osmotically drawn out of cells into the blood and the kidneys eventually begin to dump glucose into the urine. This results in loss of water and an increase in blood osmolarity. If fluid is not replaced (by mouth or intravenously), the osmotic effect of high glucose levels, combined with the loss of water, will eventually lead to dehydration. The body's cells become progressively dehydrated as water is taken from them and excreted. Electrolyte imbalances are also common and are always dangerous. As with DKA, urgent medical treatment is necessary, commonly beginning with fluid volume replacement. Lethargy may ultimately progress to a coma, though this is more common in type 2 diabetes than type 1.

Hypoglycemia
Hypoglycemia, or abnormally low blood glucose, is an acute complication of several diabetes treatments. It is rare otherwise, either in diabetic or non-diabetic patients. The patient may become agitated, sweaty, and have many symptoms of sympathetic activation of the autonomic nervous system resulting in feelings akin to dread and immobilized panic. Consciousness can be altered or even lost in extreme cases, leading to coma, seizures, or even brain damage and death. In patients with diabetes, this may be caused by several factors, such as too much or incorrectly timed insulin, too much or incorrectly timed exercise (exercise decreases insulin requirements) or not enough food (specifically glucose containing carbohydrates). The variety of interactions makes cause identification difficult in many instances.

It is more accurate to note that iatrogenic hypoglycemia is typically the result of the interplay of absolute (or relative) insulin excess and compromised glucose counterregulation in type 1 and advanced type 2 diabetes. Decrements in insulin, increments in glucagon, and, absent the latter, increments in epinephrine are the primary glucose counterregulatory factors that normally prevent or (more or less rapidly) correct hypoglycemia. In insulin-deficient diabetes (exogenous) insulin levels do not decrease as glucose levels fall, and the combination of deficient glucagon and epinephrine responses causes defective glucose counterregulation.

Furthermore, reduced sympathoadrenal responses can cause hypoglycemia unawareness. The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes posits that recent incidents of hypoglycemia causes both defective glucose counterregulation and hypoglycemia unawareness. By shifting glycemic thresholds for the sympathoadrenal (including epinephrine) and the resulting neurogenic responses to lower plasma glucose concentrations, antecedent hypoglycemia leads to a vicious cycle of recurrent hypoglycemia and further impairment of glucose counterregulation. In many cases (but not all), short-term avoidance of hypoglycemia reverses hypoglycemia unawareness in affected patients, although this is easier in theory than in clinical experience.

In most cases, hypoglycemia is treated with sugary drinks or food. In severe cases, an injection of glucagon (a hormone with the opposite effects of insulin) or an intravenous infusion of dextrose is used for treatment, but usually only if the person is unconscious. In any given incident, glucogon will only work once as it uses stored liver glycogen as a glucose source; in the absence of such stores, glucagon is largely ineffective. In hospitals, intravenous dextrose is often used.

Chronic Complications

Vascular disease
Chronic elevation of blood glucose level leads to damage of blood vessels (angiopathy). The endothelial cells lining the blood vessels take in more glucose than normal, since they don't depend on insulin. They then form more surface glycoproteins than normal, and cause the basement membrane to grow thicker and weaker. In diabetes, the resulting problems are grouped under "microvascular disease" (due to damage to small blood vessels) and "macrovascular disease" (due to damage to the arteries).

The damage to small blood vessels leads to a microangiopathy, which can cause one or more of the following:

• Diabetic retinopathy, growth of friable and poor-quality new blood vessels in the retina as well as macular edema (swelling of the macula), which can lead to severe vision loss or blindness. Retinal damage (from microangiopathy) makes it the most common cause of blindness among non-elderly adults in the U.S.
• Diabetic neuropathy, abnormal and decreased sensation, usually in a 'glove and stocking' distribution starting with the feet but potentially in other nerves, later often fingers and hands. When combined with damaged blood vessels this can lead to diabetic foot (see below). Other forms of diabetic neuropathy may present as mononeuritis or autonomic neuropathy. Diabetic amyotrophy is muscle weakness due to neuropathy.
• Diabetic nephropathy, damage to the kidney which can lead to chronic renal failure, eventually requiring dialysis. Diabetes mellitus is the most common cause of adult kidney failure worldwide in the developed world.
• Diabetic cardiomyopathy, damage to the heart, leading to diastolic dysfunction and eventually heart failure.
• Macrovascular disease leads to cardiovascular disease, to which accelerated atherosclerosis is a contributor:
• Coronary artery disease, leading to angina or myocardial infarction ("heart attack")
• Stroke (mainly the ischemic type)
• Peripheral vascular disease, which contributes to intermittent claudication (exertion-related leg and foot pain) as well as diabetic foot.
• Diabetic myonecrosis ('muscle wasting')

Diabetic foot, often due to a combination of sensory neuropathy (numbness or insensitivity) and vascular damage, increase rates of skin ulcers and infection and, in serious cases, necrosis and gangrene. It is why diabetics are prone to leg and foot infections and why it takes longer for them to heal from leg and foot wounds. It is the most common cause of non-traumatic adult amputation, usually of toes and or feet, in the developed world.

Carotid artery stenosis does not occur more often in diabetes, and there appears to be a lower prevalence of abdominal aortic aneurysm. However, diabetes does cause higher morbidity, mortality and operative risks with these conditions.

Diabetic encephalopathy is the increased cognitive decline and risk of dementia observed in diabetes. Various mechanisms are proposed, including alterations to the vascular supply of the brain and the interaction of insulin with the brain itself.