NR 566 Week 1 Notes Ch. 33
Chapter 33: Diabetes Mellitus
Intro
DM is the leading cause of blindness, lower extremity amputations, and end-stage renal disease, and
a major cause of heart disease and stroke.
Diabetes is the seventh leading cause of death in the United States, but may be underreported.
Diabetes mellitus is a chronic, progressive metabolic disorder from abnormalities in glucose, protein,
and fat metabolism, which results in hyperglycemia.
categorized into four clinical classes:
1. Type 1 diabetes
2. Type 2 diabetes
3. Diabetes due to other causes, e.g., genetic defects in beta-cell function, genetic defects in
insulin action, diseases of the exocrine pancreas (such as cystic fibrosis), and drug- or
chemical-induced causes (such as in the treatment of HIV/AIDS or after organ
transplantation)
4. Gestational diabetes mellitus (GDM), which is diagnosed during pregnancy but is not overt
after delivery
clearly interrelated with hyperlipidemia, hypertension, and coronary heart disease. Because these
disorders go hand in hand with DM, treatment protocols now include management of all these
disorders as part of diabetes management
Pathophysiology
Type I
an autoimmune destruction of the beta cells of the islet of Langerhans of the pancreas and leads to
absolute insulin deficiency
Risk factors can be genetic, autoimmune, and environmental. Seventy percent of type 1 cases are
diagnosed before the age of 30, although type 1 can occur at any age
two subtypes:
1. immune mediated (autoimmune disease)
2. nonimmune (idiopathic).
Active autoimmunity directed at the pancreatic beta cells and their products are the first
identification of type 1.
Autoantibodies to tyrosine phosphatases IA-2 and IA-2 beta to islet cells, to insulin, and to glutamic
acid decarboxylase (GAD65) are seen in 85% to 90% of patients with the immune-related subtype
A small percentage (10% to 15%) of patients with type 1 DM have no known etiology (idiopathic).
o Most patients with idiopathic type 1 DM are African American or Asian American.
When a person with the appropriate genetic characteristics is exposed to a trigger, the beta cells are
destroyed directly or when an autoimmune process is triggered, which in turn destroys the beta cells.
o Environmental factors such as toxins, food antigens, and viral infections are suspected to be
responsible for the induction of type 1
long preclinical period.
Signs and symptoms and clinical presentation of type 1 are abrupt, although a decline in insulin
secretion begins long before the symptoms develop, (possibly as long as 9 years before clinical
presentation)
80% to 90% of the function of insulin-secreting beta cells must be lost before hyperglycemia occurs
If the disease progresses without treatment, diabetic ketoacidosis (DKA), weight loss, muscle
wasting, and death may occur.
Once treatment is initiated, the patient may enter temporary partial remission, despite the continued
destruction of beta cells (“honeymoon phase”).
Beta cell destruction eventually reaches a point at which hyperglycemia occurs again, and insulin
therapy is required throughout the rest of the disease proces
Type 2
more common, affects 90-95% of people with DM
, type 2 varies in the United States by ethnic group, with a higher frequency in Native Americans, Asian
Americans, Latinos, Pacific Islanders, and African Americans
Other risk factors include obesity, sedentary lifestyle, hypertension, dyslipidemias, family history,
gestational history, and age
multifactorial
symptoms vary greatly
main physiological alteration in type 2 DM is insulin resistance and/or decreased insulin secretion.
o Insulin resistance is a suboptimal response of sensitivity to insulin, especially in the liver,
muscle, and adipose tissue. The result is an increased rate of endogenous glucose production
secondary to increased glucagon levels
GLP-1 is deficient in people with DM and pre-DM and contributes to the excessive hepatic glucose
production, lack of postprandial glucagon suppression, and uncontrolled eating
Many years of compensatory hyperinsulinemia may occur before the onset of clinical symptoms of
diabetes. Eventually, the beta cell responsiveness to glucose stimulus diminishes and hyperglycemia
prevails
Adipose tissue does not use glucose in response to insulin, resulting in obesity and a large amount of fat
in the bloodstream, which results in increased plasma Free Fatty Acids levels.
Increased visceral fat shows an inverse relationship with insulin sensitivity obesity triples the risk for
insulin resistance
Insulin resistance has also been linked to three other important disorders: hyperlipidemia, hypertension,
and coronary artery disease.
insulin has a direct antiplatelet effect, and loss of insulin results in increased adhesiveness and
exaggerated aggregation and thrombus generation
Characteristic Type 1 Type 2
Age at onset Usually during childhood or Usually after age 40 and risk for it increases
adolescence, but can occur at any with age, obesity, and lack of physical
age, even in eighth and ninth activity
decades
Type of onset Signs and symptoms abrupt, but Insidious and gradual
disease process may be present for
years
Genetic susceptibility HLA-DR3 and DR4 and others; 50% Frequent genetic background, but no
concordance in monozygotic twins relation to HLA; almost 100% concordance
in monozygotic twins
Environmental factors Viruses, toxins Obesity, nutrition; more common in women
with prior gestational diabetes and in
patients with hypertension or hyperlipidemia
Etiology Unknown; postulated causes include Unknown; heredity is highly associated
heredity, autoimmune disease, and
viral infections
Islet cell antibody and Present at onset Absent
pancreatic cell-mediated
immunity
Endogenous insulin Secretion is markedly diminished Levels may be low (insulin deficiency),
early in disease; may be totally normal, or high (insulin resistance)
absent later
Nutritional status Thin, catabolic state Obesity is common
, Characteristic Type 1 Type 2
Symptoms Polydipsia, polyphagia, polyuria, May be asymptomatic; polydipsia or
fatigue, and weight loss polyuria may be present
Ketosis At onset or during insulin deficiency Resistant except during infection or stress
Control of blood sugars Often difficult with wide glucose Variable
fluctuations
Dietary management Essential Essential; sometimes controlled with diet
and exercise
Insulin Insulin therapy required Usually required as disease progresses
Metformin, sulfonylureas, Not efficacious Efficacious
and other oral agents
Complications Occur in a majority of patients after Frequent, but reduced incidence for those
>5 yr, but reduced incidence for with good control
those with good control
Diagnostic Criteria
Diagnostic
Category Diagnostic Criteria
Diabetes Acute symptoms of diabetes plus casual plasma glucose concentration ≥200 mg/dL.
mellitus *Casual is defined as any time of day without regard to time since last meal. The classic
symptoms of diabetes are polyuria, polydipsia, and unexplained weight loss.
Fasting plasma glucose ≥126 mg/dL. * Fasting is defined as no caloric intake for at least 8
h.
2-h postload plasma glucose in an oral glucose tolerance test ≥200 mg/dL. The test uses a
glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.
Hb A1c ≥6.5%
Pre-diabetes Fasting plasma glucose 100–125 mg/dL (IFG) or
plasma glucose 140–199 mg/dL (IGT) 2 hr post-ingestion of standard glucose load (75 g) or
Hb A1c 5.7%–6.4%
Pharmacodynamics
insulin
Administration of the exogenous insulin produces the same effect as the naturally occurring hormone
Insulin lowers blood glucose levels by the following mechanisms
o Promotes protein synthesis by increasing amino acid transport into cells
o Stimulates glucose entry into cells as energy source
o Increases storage of glucose as glycogen (glycogenesis) in muscle and liver cells
o Inhibits glucose production in liver and muscle cells (glycogenolysis)
o Enhances fat storage (lipogenosis) and prevents mobilization of fat for energy (lipolysis and
ketogenesis)
o Inhibits glucose formation from noncarbohydrate sources, such as amino acids (gluconeogenesis)
Chapter 33: Diabetes Mellitus
Intro
DM is the leading cause of blindness, lower extremity amputations, and end-stage renal disease, and
a major cause of heart disease and stroke.
Diabetes is the seventh leading cause of death in the United States, but may be underreported.
Diabetes mellitus is a chronic, progressive metabolic disorder from abnormalities in glucose, protein,
and fat metabolism, which results in hyperglycemia.
categorized into four clinical classes:
1. Type 1 diabetes
2. Type 2 diabetes
3. Diabetes due to other causes, e.g., genetic defects in beta-cell function, genetic defects in
insulin action, diseases of the exocrine pancreas (such as cystic fibrosis), and drug- or
chemical-induced causes (such as in the treatment of HIV/AIDS or after organ
transplantation)
4. Gestational diabetes mellitus (GDM), which is diagnosed during pregnancy but is not overt
after delivery
clearly interrelated with hyperlipidemia, hypertension, and coronary heart disease. Because these
disorders go hand in hand with DM, treatment protocols now include management of all these
disorders as part of diabetes management
Pathophysiology
Type I
an autoimmune destruction of the beta cells of the islet of Langerhans of the pancreas and leads to
absolute insulin deficiency
Risk factors can be genetic, autoimmune, and environmental. Seventy percent of type 1 cases are
diagnosed before the age of 30, although type 1 can occur at any age
two subtypes:
1. immune mediated (autoimmune disease)
2. nonimmune (idiopathic).
Active autoimmunity directed at the pancreatic beta cells and their products are the first
identification of type 1.
Autoantibodies to tyrosine phosphatases IA-2 and IA-2 beta to islet cells, to insulin, and to glutamic
acid decarboxylase (GAD65) are seen in 85% to 90% of patients with the immune-related subtype
A small percentage (10% to 15%) of patients with type 1 DM have no known etiology (idiopathic).
o Most patients with idiopathic type 1 DM are African American or Asian American.
When a person with the appropriate genetic characteristics is exposed to a trigger, the beta cells are
destroyed directly or when an autoimmune process is triggered, which in turn destroys the beta cells.
o Environmental factors such as toxins, food antigens, and viral infections are suspected to be
responsible for the induction of type 1
long preclinical period.
Signs and symptoms and clinical presentation of type 1 are abrupt, although a decline in insulin
secretion begins long before the symptoms develop, (possibly as long as 9 years before clinical
presentation)
80% to 90% of the function of insulin-secreting beta cells must be lost before hyperglycemia occurs
If the disease progresses without treatment, diabetic ketoacidosis (DKA), weight loss, muscle
wasting, and death may occur.
Once treatment is initiated, the patient may enter temporary partial remission, despite the continued
destruction of beta cells (“honeymoon phase”).
Beta cell destruction eventually reaches a point at which hyperglycemia occurs again, and insulin
therapy is required throughout the rest of the disease proces
Type 2
more common, affects 90-95% of people with DM
, type 2 varies in the United States by ethnic group, with a higher frequency in Native Americans, Asian
Americans, Latinos, Pacific Islanders, and African Americans
Other risk factors include obesity, sedentary lifestyle, hypertension, dyslipidemias, family history,
gestational history, and age
multifactorial
symptoms vary greatly
main physiological alteration in type 2 DM is insulin resistance and/or decreased insulin secretion.
o Insulin resistance is a suboptimal response of sensitivity to insulin, especially in the liver,
muscle, and adipose tissue. The result is an increased rate of endogenous glucose production
secondary to increased glucagon levels
GLP-1 is deficient in people with DM and pre-DM and contributes to the excessive hepatic glucose
production, lack of postprandial glucagon suppression, and uncontrolled eating
Many years of compensatory hyperinsulinemia may occur before the onset of clinical symptoms of
diabetes. Eventually, the beta cell responsiveness to glucose stimulus diminishes and hyperglycemia
prevails
Adipose tissue does not use glucose in response to insulin, resulting in obesity and a large amount of fat
in the bloodstream, which results in increased plasma Free Fatty Acids levels.
Increased visceral fat shows an inverse relationship with insulin sensitivity obesity triples the risk for
insulin resistance
Insulin resistance has also been linked to three other important disorders: hyperlipidemia, hypertension,
and coronary artery disease.
insulin has a direct antiplatelet effect, and loss of insulin results in increased adhesiveness and
exaggerated aggregation and thrombus generation
Characteristic Type 1 Type 2
Age at onset Usually during childhood or Usually after age 40 and risk for it increases
adolescence, but can occur at any with age, obesity, and lack of physical
age, even in eighth and ninth activity
decades
Type of onset Signs and symptoms abrupt, but Insidious and gradual
disease process may be present for
years
Genetic susceptibility HLA-DR3 and DR4 and others; 50% Frequent genetic background, but no
concordance in monozygotic twins relation to HLA; almost 100% concordance
in monozygotic twins
Environmental factors Viruses, toxins Obesity, nutrition; more common in women
with prior gestational diabetes and in
patients with hypertension or hyperlipidemia
Etiology Unknown; postulated causes include Unknown; heredity is highly associated
heredity, autoimmune disease, and
viral infections
Islet cell antibody and Present at onset Absent
pancreatic cell-mediated
immunity
Endogenous insulin Secretion is markedly diminished Levels may be low (insulin deficiency),
early in disease; may be totally normal, or high (insulin resistance)
absent later
Nutritional status Thin, catabolic state Obesity is common
, Characteristic Type 1 Type 2
Symptoms Polydipsia, polyphagia, polyuria, May be asymptomatic; polydipsia or
fatigue, and weight loss polyuria may be present
Ketosis At onset or during insulin deficiency Resistant except during infection or stress
Control of blood sugars Often difficult with wide glucose Variable
fluctuations
Dietary management Essential Essential; sometimes controlled with diet
and exercise
Insulin Insulin therapy required Usually required as disease progresses
Metformin, sulfonylureas, Not efficacious Efficacious
and other oral agents
Complications Occur in a majority of patients after Frequent, but reduced incidence for those
>5 yr, but reduced incidence for with good control
those with good control
Diagnostic Criteria
Diagnostic
Category Diagnostic Criteria
Diabetes Acute symptoms of diabetes plus casual plasma glucose concentration ≥200 mg/dL.
mellitus *Casual is defined as any time of day without regard to time since last meal. The classic
symptoms of diabetes are polyuria, polydipsia, and unexplained weight loss.
Fasting plasma glucose ≥126 mg/dL. * Fasting is defined as no caloric intake for at least 8
h.
2-h postload plasma glucose in an oral glucose tolerance test ≥200 mg/dL. The test uses a
glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.
Hb A1c ≥6.5%
Pre-diabetes Fasting plasma glucose 100–125 mg/dL (IFG) or
plasma glucose 140–199 mg/dL (IGT) 2 hr post-ingestion of standard glucose load (75 g) or
Hb A1c 5.7%–6.4%
Pharmacodynamics
insulin
Administration of the exogenous insulin produces the same effect as the naturally occurring hormone
Insulin lowers blood glucose levels by the following mechanisms
o Promotes protein synthesis by increasing amino acid transport into cells
o Stimulates glucose entry into cells as energy source
o Increases storage of glucose as glycogen (glycogenesis) in muscle and liver cells
o Inhibits glucose production in liver and muscle cells (glycogenolysis)
o Enhances fat storage (lipogenosis) and prevents mobilization of fat for energy (lipolysis and
ketogenesis)
o Inhibits glucose formation from noncarbohydrate sources, such as amino acids (gluconeogenesis)
