Atlas of pathophysiology, 2 Edition

Part II - Disorders

Endocrine Disorders

Diabetes mellitus

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia resulting from lack of insulin, lack of insulin effect, or both. Three general classifications are recognized:

·   type 1—absolute insulin insufficiency

·   type 2—insulin resistance with varying degrees of insulin secretory defects

·   gestational diabetes—manifested during pregnancy.

Age Alert

Although possible at any age, type 1 usually manifests before age 30. It requires exogenous insulin and dietary management.

Type 2 usually occurs in obese adults after age 40. It's treated with diet and exercise combined with various antidiabetic drugs; treatment may include insulin therapy.


·   Heredity

·   Environment (infection, toxins)

·   Stress, diet, lack of exercise in genetically susceptible persons

·   Pregnancy


Type 1 and type 2 diabetes mellitus are two separate and distinct pathophysiological entities. In persons genetically susceptible to type 1 diabetes, a triggering event, possibly a viral infection, causes production of autoantibodies which kill the beta cells of the pancreas. This leads to a decline in and an ultimate lack of insulin secretion. Insulin deficiency, when more than 90% of the beta cells have been destroyed, leads to hyperglycemia, enhanced lipolysis, and protein catabolism.

Type 2 diabetes mellitus is a chronic disease caused by one or more of the following factors: impaired insulin production, inappropriate hepatic glucose production, or peripheral insulin receptor insensitivity.

Gestational diabetes mellitus is glucose intolerance during pregnancy in a woman not previously diagnosed with diabetes. This may occur if placental hormones counteract insulin, causing insulin resistance.

Signs and symptoms

·   Polyuria and polydipsia

·   Nausea; anorexia (common) or polyphagia (occasional)

·   Weight loss (usually 10% to 30%; persons with type 1 diabetes often have almost no body fat at diagnosis)

·   Headaches, fatigue, lethargy, reduced energy levels, impaired school or work performance

·   Muscle cramps, irritability, emotional lability

·   Vision changes such as blurring

·   Numbness and tingling

·   Abdominal discomfort and pain; diarrhea or constipation

·   Recurrent vaginal candidiasis

Diagnostic test results

In men and nonpregnant women

·   Two of the following criteria obtained more than 24 hours apart, using the same test twice or any combination are indicators of the disease:

§  fasting plasma glucose level of 126 mg/dl or more on at least two occasions

§  typical symptoms of uncontrolled diabetes and random blood glucose level of 200 mg/dl or more

§  blood glucose level of 200 mg/dl or more 2 hours after ingesting 75 g of oral dextrose.

·   Other criteria include:

§  diabetic retinopathy on ophthalmologic examination

§  other diagnostic and monitoring tests, including urinalysis for acetone and glycosylated hemoglobin (reflects glycemic control over the past 2 to 3 months).

In pregnant women

·   Positive glucose tolerance test reveals high peak blood sugar levels after ingestion of glucose (1 g/kg body weight) and delayed return to fasting levels.


Type 1 diabetes mellitus

·   Insulin replacement, meal planning, and exercise (current forms of insulin replacement include mixed-dose, split mixed-dose, and multiple daily injection regimens and continuous subcutaneous insulin infusions)

·   Pancreas transplantation (currently requires chronic immunosuppression)

Type 2 diabetes mellitus

·   Oral antidiabetic drugs to stimulate endogenous insulin production, increase insulin sensitivity at the cellular level, suppress hepatic gluconeogenesis, and delay GI absorption of carbohydrates (drug combinations may be used)

·   Exogenous insulin, alone or with oral antidiabetic drugs, to optimize glycemic control

Type 1 and type 2 diabetes mellitus

·   Individualized meal plan designed to meet nutritional needs, control blood glucose and lipid levels, and reach and maintain appropriate body weight

·   Weight reduction (obese patient with type 2 diabetes mellitus) or high calorie allotment, depending on growth stage and activity level (type 1 diabetes mellitus)

Gestational diabetes

·   Medical nutrition therapy and exercise

·   Alpha glucosidase inhibitors, injected insulin, or both (if euglycemia not achieved)

·   Counseling on the high risk for gestational diabetes in subsequent pregnancies and type 2 diabetes later in life

·   Exercise and weight control to help avert type 2 diabetes

Clinical Tip

Although patients with type 2 diabetes are able to suppress development of ketones under basal conditions, they may develop diabetic ketoacidosis in the presence of precipitating factors such as sepsis.