Essentials of Anatomy and Physiology

238 The Endocrine System

BOX10–3 DIABETES MELLITUS

more water is lost as well, symptoms include

greater urinary output (polyuria) and thirst (poly-

dipsia).

The long-term effects of hyperglycemia produce

distinctive vascular changes. The capillary walls

thicken, and exchange of gases and nutrients

diminishes. The most damaging effects are seen in

the skin (especially of the feet), the retina (diabetic

retinopathy), and the kidneys. Poorly controlled

diabetes may lead to dry gangrene, blindness, and

severe kidney damage. Atherosclerosis is common,

because faulty triglyceride metabolism is linked to

faulty glucose metabolism. Neuropathy (damage to

nerves) leads to impaired cutaneous sensation and

difficulty with fine movements, such as buttoning a

shirt. It is now possible for diabetics to prevent

much of this tissue damage by precise monitoring

of the blood glucose level and more frequent

administration of insulin. Insulin pumps are able to

more closely mimic the natural secretion of insulin.

A very serious potential problem for the type 1

diabetic is ketoacidosis. When glucose cannot be

used for energy, the body turns to fats and proteins,

which are converted by the liver to ketones.

Ketones are organic acids (acetone, acetoacetic

acid) that can be used in cell respiration, but cells

are not able to utilize them rapidly so ketones

accumulate in the blood. Ketones are acids, and

lower the pH of the blood as they accumulate. The

kidneys excrete excess ketones, but in doing so

excrete more water as well, which leads to dehy-

dration and worsens the acidosis. Without adminis-

tration of insulin to permit the use of glucose, and

IV fluids to restore blood volume to normal, ketoaci-

dosis will progress to coma and death.

There are two types of diabetes mellitus: Type 1

is called insulin-dependent diabetes and its onset is

usually in childhood (juvenile onset). Type 2

is called non–insulin-dependent diabetes, and its

onset is usually later in life (maturity onset).

Type 1diabetes is characterized by destruction

of the beta cells of the islets of Langerhans and a

complete lack of insulin (see Box Figure 10–A);

onset is usually abrupt. Destruction of the beta cells

is an autoimmune response, perhaps triggered by a

virus. There may be a genetic predisposition,

because certain HLA types are found more fre-

quently in type 1 diabetics than in other children

(see Box 11–5: HLA). Insulin by injection (inhaled

insulin is undergoing clinical trials) is essential to

control type 1 diabetes. Research is continuing on

the use of immunosuppressant medications to try

to preserve some beta cells (if diagnosis is early),

and also on the transplantation of stem cells to

replace lost beta cells.

Intype 2diabetes, insulin is produced but can-

not exert its effects on cells because of a loss of

insulin receptors on cell membranes (see Box Figure

10–A). Onset of type 2 diabetes is usually gradual,

and risk factors include a family history of diabetes

and being overweight. Control may not require

insulin, but rather medications that enable insulin

to react with the remaining membrane receptors.

For those with a family history of diabetes, a low-fat

diet and regular exercise reduce the risk of devel-

oping the disease. The commitment to exercise

must be lifelong but is well worth the effort,

because diabetes is very destructive.

Without insulin (or its effects) blood glucose level

remains high, and glucose is lost in urine. Since

A Normal B Type 1 C Type 2

Glucose

Insulin

Insulin Receptor

Box Figure 10–A (A) Cell membrane in normal state, with insulin receptors and

insulin to regulate glucose intake. (B) Cell membrane in type 1 diabetes: insulin not

present, glucose remains outside cell. (C) Cell membrane in type 2 diabetes: without

insulin receptors, glucose remains outside cell.