Ideal Pathophysiology of Type 2 Diabetes Mellitus (Book Based)

Type 2 diabetes mellitus describes a condition of fasting hyperglycemia that occurs

despite the availability of insulin. In contrast to type 1 diabetes, type 2 diabetes is not associated

with HLA markers of autoantibodies. Most people with type 2 diabetes are older and overweight.

The metabolic abnormalities that contribute to hyperglycemia in people with type 2 Diabetes

include impaired insulin secretion, peripheral insulin resistance, and increased hepatic glucose

production. Insulin resistance, and increased hepatic glucose production. Insulin resistance

initially stimulates insulin secretion from the beta cells in the pancreas to overcome the

increased demand to maintain a normoglycemic state. In time, the insulin response by the beta

cells declines because of exhaustion. In time, the insulin response by the beta cells declines

because of exhaustion. This results in elevated postprandial blood glucose levels. During the

evolutionary phase, an individual with type 2 diabetes may become insulinopenic because of

beta cell failure. Because people with type 2 diabetes do not have an absolute insulin

deficiency, they are less prone to develop ketoacidosis as compared to people with type 1

diabetes.

The pathogenesis of type 2 diabetes mellitus differs significantly from that type 1. A

limited beta cell response to hyperglycemia appears to be a major factor in its development.

Beta cells chronically exposed to high blood levels of glucose become progressively less

efficient when responding to further glucose elevations. This phenomenon, termed

desensitization, in reversible by normalizing glucose levels. The ration of proinsulin (a precursor

to insulin) to insulin secreted also increases.

A second pathophysiology progress in type 2 diabetes mellitus is resistance to the

biologic activity of insulin in both the liver and peripheral tissues. This state is known as insulin

resistance. People with type 2 diabetes have a decreased sensitivity to glucose levels, which
results in continued hepatic glucose uptake. The mechanism causing peripheral insulin

resistance is not clear; however, it appears to occur after insulin binds to a receptor on the cell

surface.

Insulin is a building (anabolic) hormone. Without insulin, three major metabolic problems

occur (1) decreased glucose utilization, (2) increased fat mobilization, and (3) increased protein

utilization.

Clinical Manifestations

Hyperglycemia, the medical term for an elevated blood glucose level, leads to common

clinical manifestations associated with diabetes. In type 2 diabetes may develop so gradually

that some affected people notice few or no manifestations for a number of years. Clients may

initially complain of chronic problems, as from peripheral neuropathy (nerve damage in hands

and feet). Other times, the diagnosis of type 2 diabetes may be made by a routine laboratory

test in clients who have no manifestations.

The classic clinical manifestations of diabetes are increased frequency of urination

(polyuria), increased thirst and fluid intake (polydipsia), and, as the disease progress, weight

loss despite increased hunger and food intake (polyphagia). These clinical manifestations are

caused by hyperglycemia and the accompanying spillover of excess glucose in urine.

Complications

Two acute metabolic complications of diabetes are diabetic ketoacidosis (DKA) and

hyperglycemic hyperosmolar nonketotic syndrome (HNKS). This life threatening conditions

require immediate medical intervention.

Patients with diabetes mellitus also have a higher risk for various chronic illnesses

affecting virtually all body systems. The most common chronic complications include

cardiovascular disease, peripheral vascular disease, retinopathy, nephropathy, diabetic

dermopathy, and peripheral and autonomic neuropathy.

Peripheral neuropathy usually affects the hands and feet and may cause numbness or

pain. Autonomic neuropathy manifests itself in several ways, including gastroparesis (leading to

delayed gastric emptying and a feeling of nausea and fullness after meals), nocturnal diarrhea,

impotence, postural hypotension.

Hyperglycemia impairs the patient’s resistance to infection because the glucose content

of the epidermis and urine encourages bacterial growth. The patient is susceptible to skin and

urinary tract infections and vaginitis.