53
Diabetes
Jane K. Dickinson
http://evolve.elsevier.com/Lewis/medsurg/
CONCEPTUAL FOCUS
Glucose Regulation Self-Management
Infection Sensory Perception
Nutrition
LEARNING OUTCOMES
1. Describe the pathophysiology and clinical manifestations of 6. Describe the nursing management of a patient with diabetes
diabetes. in the ambulatory and home care settings.
2. Distinguish between type 1 and type 2 diabetes. 7. Relate the pathophysiology of acute and chronic
3. Describe the interprofessional care of a patient with complications of diabetes to the clinical manifestations.
diabetes. 8. Explain the interprofessional care and nursing management
4. Describe the role of nutrition and exercise in managing of a patient with acute and chronic complications of
diabetes. diabetes.
5. Discuss the nursing management of a patient with newly
diagnosed diabetes.
KEY TERMS
basal-bolus plan diabetes-related retinopathy
blood glucose monitoring (BGM) hyperosmolar hyperglycemia syndrome (HHS)
dawn phenomenon impaired fasting glucose (IFG)
diabetes mellitus (DM) impaired glucose tolerance (IGT)
diabetes-related ketoacidosis (DKA) insulin resistance
diabetes-related nephropathy prediabetes
diabetes-related neuropathy Somogyi effect
This chapter presents the pathophysiology, manifestations, production, impaired insulin use, or both. DM is a prevalent and
complications, and management of diabetes (DM). The poten- growing health problem throughout the world. In the United
tial for long-term complications from DM makes it a challeng- States, an estimated 34.2 million people, or 10.5% of the popu-
ing disease. DM is associated with adult blindness, end-stage lation, have DM. Prediabetes affects 88 million adults.1 About
renal disease (ESRD), and nontraumatic lower-limb amputa- 7.3 million people with DM have not been diagnosed and are
tions. People with DM have a higher risk of heart disease and unaware that they have the disease. DM is the 7th leading cause
stroke. Managing DM requires making daily decisions about of death in the United States.2
food intake, blood glucose monitoring (BGM), medication,
and exercise. You play a vital role in promoting the patient’s Etiology and Pathophysiology
self-management of DM through providing comprehensive Current theories link the causes of DM, singly or in combina-
patient and caregiver education. tion, to genetic, autoimmune, and environmental factors (e.g.,
virus, higher weight). Regardless of its cause, DM is mainly a
disorder of glucose metabolism related to absent or insufficient
DIABETES insulin supply and/or ineffective use of the available insulin.
Diabetes mellitus (DM), or diabetes, is a chronic multisystem The American Diabetes Association (ADA) recognizes 4 dif-
disease characterized by hyperglycemia from abnormal insulin ferent classes of DM. The 2 most common are type 1 and type
1285
,1286 SECTION 11 Problems Related to Regulatory and Reproductive Mechanisms
TABLE 53.1 Comparison of Type 1 and Type 2 DM
Factor Type 1 DM Type 2 DM
Age at onset More common in young people but can occur at any age More common in adults but can occur at any age
Incidence increasing in children
Type of onset Signs and symptoms usually abrupt, although disease Gradual, may go undiagnosed for years
process may be present for several years
Prevalence Accounts for 5%–10% of all types of DM Accounts for 90%–95% of all types of DM
Endogenous insulin Absent Initially increased in response to insulin resistance. Secretion
decreases over time
Environmental factors Virus, toxins Higher weight, lack of exercise
Islet cell antibodies Often present at onset Absent
Primary defect Absent or minimal insulin production Insulin resistance, decreased insulin production over time, and
changes in adipokines production
Symptoms Polydipsia, polyuria, polyphagia, fatigue, weight loss Often none. Fatigue, recurrent infections. May also have polyuria,
without trying polydipsia, and polyphagia, blurred vision
Ketosis Present at onset or during insulin deficiency Usually not present; can occur during infection or high stress
Insulin therapy Required for all Required for some. Progressive disease. Insulin may need to be added
to treatment plan
Body type Thin, normal, or obese Often overweight or obese with visceral adiposity (“apple shape”).
May be normal
Nutrition therapy Essential Essential
Vascular and neurologic Frequent Frequent
complications
Insulin binds Glucose
Plasma insulin (µU/mL)
75 Breakfast Lunch Dinner
to receptor
50
25
4 AM 8 AM Noon 6 PM 10 PM Midnight
Time Glucose
Fig. 53.1 Normal endogenous insulin secretion. After meals, insulin enters cell
concentrations rise rapidly in blood and peak at about 1 hour. Then
insulin concentrations promptly decline toward preprandial values as
carbohydrate absorption from the GI tract declines. After carbohydrate
absorption from the GI tract is complete and during the night, insulin GLUT 4
concentrations are low and fairly constant, with a slight increase at
dawn.
Fig. 53.2 Normal glucose metabolism. Insulin binds to receptors along
the cell walls of muscle, adipose, and liver cells. Glucose transport pro-
2 DM (Table 53.1). Another type is maturity onset diabetes of teins (GLUT 4s) then attach to the cell wall and allow glucose to enter
the young (MODY). The 2 other classes are gestational DM and the cell. There it is either stored or used to make energy.
other specific types of DM with various causes.
Cells break down glucose to make energy. Liver and muscle cells
Normal Glucose and Insulin Metabolism store excess glucose as glycogen. The rise in plasma insulin after a
Insulin is a hormone made by the β cells in the islets of meal inhibits gluconeogenesis, enhances fat deposition of adipose
Langerhans of the pancreas. Under normal conditions, the tissue, and increases protein synthesis. For this reason, insulin is
pancreas continuously releases insulin into the bloodstream an anabolic, or storage, hormone. The fall in insulin level during
in small amounts. Release increases when we ingest food (Fig. normal overnight fasting promotes the release of stored glucose
53.1). Insulin lowers glucose and facilitates a stable, normal glu- from the liver, protein from muscle, and fat from adipose tissue.
cose range of about 74 to 106 mg/dL (4.1 to 5.9 mmol/L). The Skeletal muscle and adipose tissue have specific receptors for
amount of insulin secreted daily by an adult is about 40 to 50 U insulin and are considered insulin-dependent tissues. Insulin is
or 0.6 U/kg of body weight. required to “unlock” these receptor sites, allowing the transport
Insulin promotes glucose transport from the bloodstream of glucose into the cells to be used for energy. Other tissues (e.g.,
across the cell membrane to the cytoplasm of the cell (Fig. 53.2). brain, liver, blood cells) do not directly depend on insulin for
, CHAPTER 53 Diabetes 1287
BOX 53.1 GENETICS IN CLINICAL PRACTICE
Diabetes
Type 1 DM Type 2 DM MODY
Genetic Basis
• Increased susceptibility (40%–50%) when a • Polygenic (>25 genes influence susceptibility) • Autosomal dominant
person has specific human leukocyte antigens • Monogenic (single gene)
(HLA-DR3 and HLA-DR4) • Caused by mutations in any of 6 MODY genes
• Polygenic (>40 genes influence susceptibility) (types 1–6)
• Gene mutations lead to β-cell dysfunction
Risk to Offspring
• Risk to offspring of mothers with DM is 1%–4% • Risk to offspring is 8%–14% • If 1 parent has MODY, a child has a 50% chance of
• Risk to offspring of fathers with DM is 5%–6% • When 1 identical twin has type 2 DM, the other developing DM
• When 1 identical twin has type 1 DM, the other gets DM about 60%–75% of the time • If 1 parent has MODY, a child has a 50% chance of
gets DM about 30%–40% of the time being a carrier
Clinical Implications
• Result of complex interaction of genetic, autoim- • Result of complex genetic interactions and other • Accounts for 1%–5% of people with DM
mune, and environmental factors metabolic factors • Young age of onset (often before age 25)
• Environmental factors, such as body weight • Not related to obesity or hypertension
and exercise, can sometimes modify metabolic • Treatment depends on the genetic mutation that
factors caused MODY
glucose transport but require an adequate glucose supply for autoimmune process. The HLA types with an increased risk for
normal function. Although liver cells are not insulin-dependent type 1 DM include HLA-DR3 and HLA-DR4.
tissue, insulin receptor sites on the liver facilitate uptake of glu- Idiopathic diabetes is a form of type 1 DM that is strongly inher-
cose and its conversion to glycogen. ited and not related to autoimmunity. It only occurs in a small num-
Other hormones (glucagon, epinephrine, growth hormone ber of people with type 1 DM. They are most often of Hispanic,
[GH], cortisol) work against the effects of insulin. They are coun- African, or Asian ancestry.4 Latent autoimmune diabetes in adults
terregulatory hormones. These hormones increase glucose levels (LADA) is a slowly progressing autoimmune form of type 1 DM. It
by (1) stimulating glucose production and release by the liver and occurs in adults and is often mistaken for type 2 DM.
(2) decreasing the movement of glucose into the cells. The coun- Onset of disease. In type 1 DM, the islet cell autoantibodies
terregulatory hormones and insulin work together to maintain responsible for β-cell destruction are present for months to
glucose levels within the normal range by regulating the release years before the onset of symptoms. Manifestations develop
of glucose for energy during food intake and periods of fasting. when the person’s pancreas can no longer make enough insulin
Insulin is synthesized from its precursor, proinsulin. to maintain normal glucose. Once this occurs, the onset of
Enzymes split proinsulin to form insulin and C-peptide. The 2 symptoms is usually rapid. Patients often present with impending
substances are released in equal amounts. Therefore, measuring or actual ketoacidosis. The patient usually has a history of recent
C-peptide in serum and urine is a useful indicator of pancreatic and sudden weight loss and the classic symptoms of polydipsia
β-cell function and insulin levels. (excessive thirst), polyuria (frequent urination), and polyphagia
(excessive hunger).
Type 1 Diabetes The person with type 1 DM requires insulin from an out-
Type 1 diabetes accounts for about 5% to 10% of all people with side source (exogenous insulin) to sustain life. Without insulin,
DM. Type 1 DM generally affects people under 40 years of age, the patient will develop diabetes-related ketoacidosis (DKA), a
although it can occur at any age.3 life-threatening condition causing metabolic acidosis. Newly
Etiology and pathophysiology. Type 1 DM is an autoimmune diagnosed patients may have a remission, or “honeymoon
disorder in which the body develops antibodies against insulin period,” for 3 to 12 months after starting treatment. During
and/or the pancreatic β cells that make insulin. This eventually this time, the patient needs little injected insulin because β-cell
results in not enough insulin for a person to survive. A genetic insulin production is still sufficient for healthy glucose levels.
predisposition and exposure to a virus are factors that may Eventually, as more β cells are destroyed, and glucose levels
contribute to developing immune-related type 1 DM (Box 53.1). increase, the honeymoon period ends. The patient then requires
insulin on a permanent basis.
Genetic Link
Predisposition to type 1 DM is related to human leukocyte Type 2 Diabetes
antigens (HLAs) (see Chapter 14). In theory, when a person Type 2 diabetes accounts for about 90% to 95% of people with
with certain HLA types is exposed to a viral infection, the β DM.5 Many risk factors contribute to developing type 2 DM.
cells of the pancreas are destroyed, either directly or through an These include having a family history of type 2 DM, being
, 1288 SECTION 11 Problems Related to Regulatory and Reproductive Mechanisms
BOX 53.2 PROMOTING HEALTH Type 1 Diabetes
EQUITY
DM
• N ative Americans and Alaska Natives have the highest prevalence of DM
(23.5%)6 Pancreas
• Rates of DM are higher among Blacks (20.4%), Hispanics (22.1%), than • Autoimmune destruction of β cells
• Autoantibodies present for months to years
among Whites (12.1%), and Asians (14.0%)6 before clinical symptoms
• Insufficient production of insulin
Type 2 Diabetes
overweight or obese, and being older. Although it occurs less
often in children, the incidence is increasing due to the increas-
ing prevalence of childhood obesity. Type 2 DM is more prev-
alent in some ethnic populations (Box 53.2). This increase is
related to genetic predisposition, environmental factors, and
diet choices. Pancreas Liver
Etiology and pathophysiology. Type 2 DM is characterized • Defective β cell secretion • Excess glucose production
of insulin • Inappropriate regulation of
by a combination of inadequate insulin secretion and insulin • Insulin resistance stimulates glucose production
resistance. The pancreas usually makes some endogenous (self- ↑ insulin secretion
• Eventual exhaustion of
made) insulin. However, the body either does not make enough β cells in many people
insulin, does not use it effectively, or both. The presence of • ↑ Glucagon secretion
endogenous insulin is a major distinction between type 1 and
type 2 DM. In type 1 DM, there is an absence of endogenous
insulin.
Genetic Link Muscle
Although we do not fully understand the genetics of type 2 DM, Adipose tissue
• Defective insulin receptors
it is likely that multiple genes are involved (Box 53.1). We have • ↓ Adiponectin and ↑ leptin • Insulin resistance
• Results in altered glucose • Decreased uptake of
found genetic mutations that lead to insulin resistance and a and fat metabolism glucose by cells resulting
higher risk for obesity in many people with type 2 DM. Persons in hyperglycemia
with a first-degree relative with the disease are 10 times more Fig. 53.3 Altered mechanisms in type 1 and type 2 DM.
likely to develop type 2 DM.
Metabolic abnormalities have a role in developing type 2
DM (Fig. 53.3). The first factor is insulin resistance. This is a tissue appear to play a role in glucose and fat metabolism. They
condition in which body tissues do not respond to the action are likely to contribute to developing type 2 DM.7 We think adi-
of insulin because insulin receptors are unresponsive, insuffi- pokines cause chronic inflammation, a factor involved in insu-
cient in number, or both. Most insulin receptors are located on lin resistance, type 2 DM, and cardiovascular disease (CVD).
skeletal muscle, fat, and liver cells. When insulin is not prop- The 2 main adipokines thought to affect insulin sensitivity are
erly used, the entry of glucose into the cell is impeded, causing adiponectin and leptin. Finally, the brain, kidneys, and gut have
hyperglycemia. In the early stages of insulin resistance, the pan- roles in developing type 2 DM. We are continuously learning
creas responds to high glucose levels by producing more insulin more about metabolic factors and developing type 2 DM.
(if β cell function is normal). This creates a temporary state of People with metabolic syndrome have an increased risk of
hyperinsulinemia that coexists with hyperglycemia. developing type 2 DM. Metabolic syndrome has 5 components:
A second factor in developing type 2 DM is a marked decrease increased glucose levels, abdominal obesity, high BP, high tri-
in the ability of the pancreas to make insulin. The β cells become glyceride levels, and decreased high-density lipoprotein (HDL)
fatigued from the compensatory overproduction of insulin levels (see Table 45.11). A person with 3 of the 5 components is
or when β-cell mass is lost. We do not know the reason the β considered to have metabolic syndrome.8 Overweight persons
cells fail to adapt. It may be due to the adverse effects of chronic with metabolic syndrome can reduce their risk for DM through
hyperglycemia or high circulating free fatty acids. In addition, food choices and regular physical activity. See Chapter 45 for
the α cells of the pancreas increase production of glucagon. more about metabolic syndrome.
This leads to a third factor, which is inappropriate glucose Onset of disease. The disease onset in type 2 DM is usually
production by the liver. Instead of properly regulating the gradual. The person may go for many years with undetected
release of glucose in response to blood levels, the liver does so hyperglycemia and few, if any, symptoms. Many people are
in a haphazard way that does not correspond to the body’s needs diagnosed on routine laboratory testing or when they undergo
at the time. treatment for other conditions, and they have high glucose or
A fourth factor is the production of hormones and cytokines glycosylated hemoglobin (A1C) levels. The signs and symptoms
by adipose tissue (adipokines). Adipokines secreted by adipose of hyperglycemia develop when about 50% to 80% of β cells are
Diabetes
Jane K. Dickinson
http://evolve.elsevier.com/Lewis/medsurg/
CONCEPTUAL FOCUS
Glucose Regulation Self-Management
Infection Sensory Perception
Nutrition
LEARNING OUTCOMES
1. Describe the pathophysiology and clinical manifestations of 6. Describe the nursing management of a patient with diabetes
diabetes. in the ambulatory and home care settings.
2. Distinguish between type 1 and type 2 diabetes. 7. Relate the pathophysiology of acute and chronic
3. Describe the interprofessional care of a patient with complications of diabetes to the clinical manifestations.
diabetes. 8. Explain the interprofessional care and nursing management
4. Describe the role of nutrition and exercise in managing of a patient with acute and chronic complications of
diabetes. diabetes.
5. Discuss the nursing management of a patient with newly
diagnosed diabetes.
KEY TERMS
basal-bolus plan diabetes-related retinopathy
blood glucose monitoring (BGM) hyperosmolar hyperglycemia syndrome (HHS)
dawn phenomenon impaired fasting glucose (IFG)
diabetes mellitus (DM) impaired glucose tolerance (IGT)
diabetes-related ketoacidosis (DKA) insulin resistance
diabetes-related nephropathy prediabetes
diabetes-related neuropathy Somogyi effect
This chapter presents the pathophysiology, manifestations, production, impaired insulin use, or both. DM is a prevalent and
complications, and management of diabetes (DM). The poten- growing health problem throughout the world. In the United
tial for long-term complications from DM makes it a challeng- States, an estimated 34.2 million people, or 10.5% of the popu-
ing disease. DM is associated with adult blindness, end-stage lation, have DM. Prediabetes affects 88 million adults.1 About
renal disease (ESRD), and nontraumatic lower-limb amputa- 7.3 million people with DM have not been diagnosed and are
tions. People with DM have a higher risk of heart disease and unaware that they have the disease. DM is the 7th leading cause
stroke. Managing DM requires making daily decisions about of death in the United States.2
food intake, blood glucose monitoring (BGM), medication,
and exercise. You play a vital role in promoting the patient’s Etiology and Pathophysiology
self-management of DM through providing comprehensive Current theories link the causes of DM, singly or in combina-
patient and caregiver education. tion, to genetic, autoimmune, and environmental factors (e.g.,
virus, higher weight). Regardless of its cause, DM is mainly a
disorder of glucose metabolism related to absent or insufficient
DIABETES insulin supply and/or ineffective use of the available insulin.
Diabetes mellitus (DM), or diabetes, is a chronic multisystem The American Diabetes Association (ADA) recognizes 4 dif-
disease characterized by hyperglycemia from abnormal insulin ferent classes of DM. The 2 most common are type 1 and type
1285
,1286 SECTION 11 Problems Related to Regulatory and Reproductive Mechanisms
TABLE 53.1 Comparison of Type 1 and Type 2 DM
Factor Type 1 DM Type 2 DM
Age at onset More common in young people but can occur at any age More common in adults but can occur at any age
Incidence increasing in children
Type of onset Signs and symptoms usually abrupt, although disease Gradual, may go undiagnosed for years
process may be present for several years
Prevalence Accounts for 5%–10% of all types of DM Accounts for 90%–95% of all types of DM
Endogenous insulin Absent Initially increased in response to insulin resistance. Secretion
decreases over time
Environmental factors Virus, toxins Higher weight, lack of exercise
Islet cell antibodies Often present at onset Absent
Primary defect Absent or minimal insulin production Insulin resistance, decreased insulin production over time, and
changes in adipokines production
Symptoms Polydipsia, polyuria, polyphagia, fatigue, weight loss Often none. Fatigue, recurrent infections. May also have polyuria,
without trying polydipsia, and polyphagia, blurred vision
Ketosis Present at onset or during insulin deficiency Usually not present; can occur during infection or high stress
Insulin therapy Required for all Required for some. Progressive disease. Insulin may need to be added
to treatment plan
Body type Thin, normal, or obese Often overweight or obese with visceral adiposity (“apple shape”).
May be normal
Nutrition therapy Essential Essential
Vascular and neurologic Frequent Frequent
complications
Insulin binds Glucose
Plasma insulin (µU/mL)
75 Breakfast Lunch Dinner
to receptor
50
25
4 AM 8 AM Noon 6 PM 10 PM Midnight
Time Glucose
Fig. 53.1 Normal endogenous insulin secretion. After meals, insulin enters cell
concentrations rise rapidly in blood and peak at about 1 hour. Then
insulin concentrations promptly decline toward preprandial values as
carbohydrate absorption from the GI tract declines. After carbohydrate
absorption from the GI tract is complete and during the night, insulin GLUT 4
concentrations are low and fairly constant, with a slight increase at
dawn.
Fig. 53.2 Normal glucose metabolism. Insulin binds to receptors along
the cell walls of muscle, adipose, and liver cells. Glucose transport pro-
2 DM (Table 53.1). Another type is maturity onset diabetes of teins (GLUT 4s) then attach to the cell wall and allow glucose to enter
the young (MODY). The 2 other classes are gestational DM and the cell. There it is either stored or used to make energy.
other specific types of DM with various causes.
Cells break down glucose to make energy. Liver and muscle cells
Normal Glucose and Insulin Metabolism store excess glucose as glycogen. The rise in plasma insulin after a
Insulin is a hormone made by the β cells in the islets of meal inhibits gluconeogenesis, enhances fat deposition of adipose
Langerhans of the pancreas. Under normal conditions, the tissue, and increases protein synthesis. For this reason, insulin is
pancreas continuously releases insulin into the bloodstream an anabolic, or storage, hormone. The fall in insulin level during
in small amounts. Release increases when we ingest food (Fig. normal overnight fasting promotes the release of stored glucose
53.1). Insulin lowers glucose and facilitates a stable, normal glu- from the liver, protein from muscle, and fat from adipose tissue.
cose range of about 74 to 106 mg/dL (4.1 to 5.9 mmol/L). The Skeletal muscle and adipose tissue have specific receptors for
amount of insulin secreted daily by an adult is about 40 to 50 U insulin and are considered insulin-dependent tissues. Insulin is
or 0.6 U/kg of body weight. required to “unlock” these receptor sites, allowing the transport
Insulin promotes glucose transport from the bloodstream of glucose into the cells to be used for energy. Other tissues (e.g.,
across the cell membrane to the cytoplasm of the cell (Fig. 53.2). brain, liver, blood cells) do not directly depend on insulin for
, CHAPTER 53 Diabetes 1287
BOX 53.1 GENETICS IN CLINICAL PRACTICE
Diabetes
Type 1 DM Type 2 DM MODY
Genetic Basis
• Increased susceptibility (40%–50%) when a • Polygenic (>25 genes influence susceptibility) • Autosomal dominant
person has specific human leukocyte antigens • Monogenic (single gene)
(HLA-DR3 and HLA-DR4) • Caused by mutations in any of 6 MODY genes
• Polygenic (>40 genes influence susceptibility) (types 1–6)
• Gene mutations lead to β-cell dysfunction
Risk to Offspring
• Risk to offspring of mothers with DM is 1%–4% • Risk to offspring is 8%–14% • If 1 parent has MODY, a child has a 50% chance of
• Risk to offspring of fathers with DM is 5%–6% • When 1 identical twin has type 2 DM, the other developing DM
• When 1 identical twin has type 1 DM, the other gets DM about 60%–75% of the time • If 1 parent has MODY, a child has a 50% chance of
gets DM about 30%–40% of the time being a carrier
Clinical Implications
• Result of complex interaction of genetic, autoim- • Result of complex genetic interactions and other • Accounts for 1%–5% of people with DM
mune, and environmental factors metabolic factors • Young age of onset (often before age 25)
• Environmental factors, such as body weight • Not related to obesity or hypertension
and exercise, can sometimes modify metabolic • Treatment depends on the genetic mutation that
factors caused MODY
glucose transport but require an adequate glucose supply for autoimmune process. The HLA types with an increased risk for
normal function. Although liver cells are not insulin-dependent type 1 DM include HLA-DR3 and HLA-DR4.
tissue, insulin receptor sites on the liver facilitate uptake of glu- Idiopathic diabetes is a form of type 1 DM that is strongly inher-
cose and its conversion to glycogen. ited and not related to autoimmunity. It only occurs in a small num-
Other hormones (glucagon, epinephrine, growth hormone ber of people with type 1 DM. They are most often of Hispanic,
[GH], cortisol) work against the effects of insulin. They are coun- African, or Asian ancestry.4 Latent autoimmune diabetes in adults
terregulatory hormones. These hormones increase glucose levels (LADA) is a slowly progressing autoimmune form of type 1 DM. It
by (1) stimulating glucose production and release by the liver and occurs in adults and is often mistaken for type 2 DM.
(2) decreasing the movement of glucose into the cells. The coun- Onset of disease. In type 1 DM, the islet cell autoantibodies
terregulatory hormones and insulin work together to maintain responsible for β-cell destruction are present for months to
glucose levels within the normal range by regulating the release years before the onset of symptoms. Manifestations develop
of glucose for energy during food intake and periods of fasting. when the person’s pancreas can no longer make enough insulin
Insulin is synthesized from its precursor, proinsulin. to maintain normal glucose. Once this occurs, the onset of
Enzymes split proinsulin to form insulin and C-peptide. The 2 symptoms is usually rapid. Patients often present with impending
substances are released in equal amounts. Therefore, measuring or actual ketoacidosis. The patient usually has a history of recent
C-peptide in serum and urine is a useful indicator of pancreatic and sudden weight loss and the classic symptoms of polydipsia
β-cell function and insulin levels. (excessive thirst), polyuria (frequent urination), and polyphagia
(excessive hunger).
Type 1 Diabetes The person with type 1 DM requires insulin from an out-
Type 1 diabetes accounts for about 5% to 10% of all people with side source (exogenous insulin) to sustain life. Without insulin,
DM. Type 1 DM generally affects people under 40 years of age, the patient will develop diabetes-related ketoacidosis (DKA), a
although it can occur at any age.3 life-threatening condition causing metabolic acidosis. Newly
Etiology and pathophysiology. Type 1 DM is an autoimmune diagnosed patients may have a remission, or “honeymoon
disorder in which the body develops antibodies against insulin period,” for 3 to 12 months after starting treatment. During
and/or the pancreatic β cells that make insulin. This eventually this time, the patient needs little injected insulin because β-cell
results in not enough insulin for a person to survive. A genetic insulin production is still sufficient for healthy glucose levels.
predisposition and exposure to a virus are factors that may Eventually, as more β cells are destroyed, and glucose levels
contribute to developing immune-related type 1 DM (Box 53.1). increase, the honeymoon period ends. The patient then requires
insulin on a permanent basis.
Genetic Link
Predisposition to type 1 DM is related to human leukocyte Type 2 Diabetes
antigens (HLAs) (see Chapter 14). In theory, when a person Type 2 diabetes accounts for about 90% to 95% of people with
with certain HLA types is exposed to a viral infection, the β DM.5 Many risk factors contribute to developing type 2 DM.
cells of the pancreas are destroyed, either directly or through an These include having a family history of type 2 DM, being
, 1288 SECTION 11 Problems Related to Regulatory and Reproductive Mechanisms
BOX 53.2 PROMOTING HEALTH Type 1 Diabetes
EQUITY
DM
• N ative Americans and Alaska Natives have the highest prevalence of DM
(23.5%)6 Pancreas
• Rates of DM are higher among Blacks (20.4%), Hispanics (22.1%), than • Autoimmune destruction of β cells
• Autoantibodies present for months to years
among Whites (12.1%), and Asians (14.0%)6 before clinical symptoms
• Insufficient production of insulin
Type 2 Diabetes
overweight or obese, and being older. Although it occurs less
often in children, the incidence is increasing due to the increas-
ing prevalence of childhood obesity. Type 2 DM is more prev-
alent in some ethnic populations (Box 53.2). This increase is
related to genetic predisposition, environmental factors, and
diet choices. Pancreas Liver
Etiology and pathophysiology. Type 2 DM is characterized • Defective β cell secretion • Excess glucose production
of insulin • Inappropriate regulation of
by a combination of inadequate insulin secretion and insulin • Insulin resistance stimulates glucose production
resistance. The pancreas usually makes some endogenous (self- ↑ insulin secretion
• Eventual exhaustion of
made) insulin. However, the body either does not make enough β cells in many people
insulin, does not use it effectively, or both. The presence of • ↑ Glucagon secretion
endogenous insulin is a major distinction between type 1 and
type 2 DM. In type 1 DM, there is an absence of endogenous
insulin.
Genetic Link Muscle
Although we do not fully understand the genetics of type 2 DM, Adipose tissue
• Defective insulin receptors
it is likely that multiple genes are involved (Box 53.1). We have • ↓ Adiponectin and ↑ leptin • Insulin resistance
• Results in altered glucose • Decreased uptake of
found genetic mutations that lead to insulin resistance and a and fat metabolism glucose by cells resulting
higher risk for obesity in many people with type 2 DM. Persons in hyperglycemia
with a first-degree relative with the disease are 10 times more Fig. 53.3 Altered mechanisms in type 1 and type 2 DM.
likely to develop type 2 DM.
Metabolic abnormalities have a role in developing type 2
DM (Fig. 53.3). The first factor is insulin resistance. This is a tissue appear to play a role in glucose and fat metabolism. They
condition in which body tissues do not respond to the action are likely to contribute to developing type 2 DM.7 We think adi-
of insulin because insulin receptors are unresponsive, insuffi- pokines cause chronic inflammation, a factor involved in insu-
cient in number, or both. Most insulin receptors are located on lin resistance, type 2 DM, and cardiovascular disease (CVD).
skeletal muscle, fat, and liver cells. When insulin is not prop- The 2 main adipokines thought to affect insulin sensitivity are
erly used, the entry of glucose into the cell is impeded, causing adiponectin and leptin. Finally, the brain, kidneys, and gut have
hyperglycemia. In the early stages of insulin resistance, the pan- roles in developing type 2 DM. We are continuously learning
creas responds to high glucose levels by producing more insulin more about metabolic factors and developing type 2 DM.
(if β cell function is normal). This creates a temporary state of People with metabolic syndrome have an increased risk of
hyperinsulinemia that coexists with hyperglycemia. developing type 2 DM. Metabolic syndrome has 5 components:
A second factor in developing type 2 DM is a marked decrease increased glucose levels, abdominal obesity, high BP, high tri-
in the ability of the pancreas to make insulin. The β cells become glyceride levels, and decreased high-density lipoprotein (HDL)
fatigued from the compensatory overproduction of insulin levels (see Table 45.11). A person with 3 of the 5 components is
or when β-cell mass is lost. We do not know the reason the β considered to have metabolic syndrome.8 Overweight persons
cells fail to adapt. It may be due to the adverse effects of chronic with metabolic syndrome can reduce their risk for DM through
hyperglycemia or high circulating free fatty acids. In addition, food choices and regular physical activity. See Chapter 45 for
the α cells of the pancreas increase production of glucagon. more about metabolic syndrome.
This leads to a third factor, which is inappropriate glucose Onset of disease. The disease onset in type 2 DM is usually
production by the liver. Instead of properly regulating the gradual. The person may go for many years with undetected
release of glucose in response to blood levels, the liver does so hyperglycemia and few, if any, symptoms. Many people are
in a haphazard way that does not correspond to the body’s needs diagnosed on routine laboratory testing or when they undergo
at the time. treatment for other conditions, and they have high glucose or
A fourth factor is the production of hormones and cytokines glycosylated hemoglobin (A1C) levels. The signs and symptoms
by adipose tissue (adipokines). Adipokines secreted by adipose of hyperglycemia develop when about 50% to 80% of β cells are
