Acute complications of diabetes mellitus
The acute complications of diabetes mellitus are nonketotic hyperglycemic hyperosmolar coma and diabetic ketoacidosis. Either of these, if not recognized promptly and treated aggressively, can lead to death. These complications should be considered as part of a continuum of hyperglycemia rather than as separate entities; the main difference between the 2 is whether ketoacids accumulate. Both are often precipitated by some type of stress, such as an infection, that leads to increased production of glucagon, catecholamines, and cortisol, which in turn promotes gluconeogenesis. If not treated with adequate amounts of insulin or oral hypoglycemic agents, the elevated glucose level will lead to osmotic diuresis and volume depletion. When insulin levels are extremely low or absent (eg, in a patient with type 1 DM), catabolic processes (eg, conversion of lipids to ketones) prevail and ketoacids are produced, superimposing severe metabolic acidosis on the hyperosmotic volume-depleted state.
Long-term complications of diabetes mellitus
The long-term complications of DM are usually secondary to vascular disease. Nephropathy, neuropathy, peripheral artery disease, coronary atherosclerosis, secondary cerebral thrombosis, cardiac infarction, and retinopathy are all important causes of morbidity and mortality. The precise mechanism for the development of diabetic complications is elusive, but hyperglycemia plays a central role by triggering a number of processes that ultimately cause vascular damage. (Diabetic retinopathy is discussed in BCSC Section 12, Retina and Vitreous.)
The blood glucose level is not the only risk factor that can be modified to reduce the complications of DM. In particular, hypertension and lipid abnormalities seem to be inextricably intertwined with glycemic control. Thus, any attempt to minimize complications must include aggressive control of these other factors.
Nephropathy Approximately 40% of patients who have had DM for 20 or more years have nephropathy. Albuminuria greater than 300 mg/24 hours—approximately the level at which a standard urine dipstick test becomes positive—is the hallmark of diabetic nephropathy. Renal failure eventually occurs in approximately 50% of patients who developed diabetes mellitus before age 20 and in 6% of those with onset after 40 years of age. Diabetic nephropathy is the leading cause of end-stage renal disease, and the 5-year survival rate of patients with DM on maintenance dialysis is less than 20%. Almost invariably, nephropathy and retinopathy develop within a short time of each other.
The progression of diabetic nephropathy occurs in the following sequence: microalbuminuria (urine albumin levels of 30–300 mg/24 hours), macroalbuminuria (urine albumin levels >300 mg/24 hours), nephrotic syndrome, and finally end-stage renal disease. Tight control of blood glucose can delay and perhaps prevent the development of microalbuminuria. In addition, controlling hypertension (particularly with angiotensin-converting enzyme inhibitors) and adhering to low-protein diets may help slow the decline in glomerular filtration rate.
Neuropathy Diabetic neuropathy is a common problem. After 30 years of DM, about 50% of patients have signs of neuropathy, and 15%–20% have symptoms of distal symmetric polyneuropathy. Changes in nerve metabolism and function are thought to be mediated in part through increased aldose reductase activity; Schwann cell synthesis of myelin is impaired, and axonal degeneration ensues. In addition, microangiopathy of the endoneural capillaries leads to vascular abnormalities and microinfarcts of the nerves, with multifocal fiber loss.
Symptoms in the feet and lower legs are the most common manifestations. Foot pain, paresthesias, and loss of sensation occur frequently and probably result from both ischemic and metabolic nerve abnormalities. Weakness may be present as part of mononeuritis or a mononeuritis multiplex and is usually associated with pain. Cranial neuropathies may also occur (see BCSC Section 5, Neuro-Ophthalmology). Additional types of morbidity, stemming from autonomic dysfunction, include male and female sexual dysfunction, impaired urination, delayed gastric emptying, orthostatic hypotension, and tachycardia due to loss of vagal tone.
There is no specific treatment for diabetic neuropathy. Aldose reductase inhibitors (not yet commercially available) may improve nerve conduction slightly but do not result in major clinical improvement. Neuropathic pain may respond to tricyclic antidepressants or capsaicin cream. Anticonvulsant drugs such as carbamazepine and gabapentin may also be useful.
Large-vessel disease The risk of coronary heart disease is 2–10 times higher in patients with DM than in the general population, and the mortality rate in patients with DM who have anterior myocardial infarctions is twice that in patients who do not have DM. Because myocardial infarction may present without the classic symptom of chest pain in patients with DM, an increased index of suspicion is required to make the diagnosis. Hypertension further increases the risk of cardiovascular disease for persons with DM. Cerebral thrombosis is approximately twice as prevalent in the diabetic population as in the nondiabetic population, and peripheral artery disease is 40 times as prevalent.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.