DIABETES MELLITUS TYPE 2
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Pathophysiology of Diabetes Mellitus Type 2
Diabetes mellitus type 2 is no longer a disease that primarily affects adults and the
number of cases diagnosed each year is rising. According to the American Diabetes Association,
25.8 million adults and children in the United States have diabetes (Diabetes Statistics, 2011).
Diabetes mellitus type 2 affects 90-95% of individuals with diabetes in the United States
(Copstead & Banasik, 2010, p. 949). Diabetes Mellitus Type 2, formerly called non-insulin
dependent diabetes and adult-onset diabetes, is a chronic, multisystem, metabolic syndrome of
gradual onset characterized by insufficient body tissue response to insulin (i.e., insulin
resistance) and impaired pancreatic production of insulin (Strayer & Schub, 2011, "Diabetes
Mellitus, Type 2," para.1). Individuals with type 2 diabetes mellitus are resistant to the action of
insulin on peripheral tissues (Copstead & Banasik, 2010, p. 949). Abnormalities of insulin
resistance and impaired production of insulin leads to the elevation of serum blood glucose,
resulting in a condition called hyperglycemia.
Individuals with diabetes mellitus type 2 have
elevated fasting blood glucose and post-prandial plasma glucose results (Surampudi, JohnKalarickal, and Fonseca, 2009, p. 216). Prolonged excessive hyperglycemia eventually leads to
devastating multisystem damage (Copstead & Banasik, 2010, p. 903).
In a normal state, the body produces insulin, a hormone secreted by the beta cells of the
pancreas in response to elevated blood sugar (Copstead & Banasik, 2010, p. 973). Insulin is
responsible for a number of key functions in the body. The amount of insulin released is
dependent upon whether a person has eaten or not. Under normal circumstances, insulin is
secreted in two phases. Initially, there is a brief rise of insulin in response to a meal ingested and
this is termed first phase. Hicks (2010) explained the first phase is "followed by a prolonged
pulsatile phase, which lowers the blood glucose level back to normal levels." In diabetes
DIABETES MELLITUS TYPE 2
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mellitus, type 2, this two step process malfunctions. Individuals with type 2 diabetes mellitus
ultimately have an absent first-phase response and a diminished second-phase response
(Copstead & Banasik, 2010, p. 949).
Over time glucose toxicity occurs and causes a
desensitization of the cells in the body to glucose, which results in an impaired insulin response
in the beta cells (Hicks, 2010, p. 49).
Persons with type 2 diabetes have a relative insulin deficiency caused by decreased tissue
sensitivity and decreased responsiveness to insulin. Insulin resistance may be defined as a
subnormal biological response to a given concentration of insulin (Surampudi, et al., 2009, p.
217). A decreased number of insulin receptors or abnormal translocation of glucose transporters
is suspected (Copstead & Banasik, 2010, p. 952). The article written by Sarampudi, et al.,
(2009) suggests:
Some of the results of insulin resistance include the overproduction of glucose by the
liver (despite fasting hyperinsulinemia and hyperglycemia) and decreased tissue
clearance by peripheral tissues. Adipose cells appear to play an important role in the
development of insulin resistance.
Elevated free fatty acids appear to stimulate
glyconeogenesis, induce hepatic insulin resistance (through inhibition of the insulin
signal transduction system), and decrease peripheral glucose clearance because of
inhibitory effects on multiple steps in the metabolism of glucose and insulin action
(Surampudi et al., 2009, p. 218).
The progression of normal glucose tolerance to impaired glucose tolerance occurs in
stages. The progression is due to the interplay between insulin resistance and defects in insulin
secretion (Surampudi et al., 2009, p. 216). The body produces more insulin, at first in an attempt
to compensate for insulin resistance at the cellular level.
Subjects with impaired glucose
DIABETES MELLITUS TYPE 2
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tolerance typically have increased fasting and post prandial insulin levels that do not fully
compensate for insulin resistance (Surampudi et al., 2009, p. 216). Decompensation occurs as
the impaired beta cells are unable to produce sufficient insulin to overcome insulin resistance
(Copstead & Banasik, 2010, p. 949). Over time, the beta cells become exhausted and begin to
fail, leading to reduced insulin production and ultimately hyperglycemia (Hicks, 2010, p. 49).
Under conditions of normal physiology, insulin lowers blood glucose by acting as a
protein transporter of glucose from the bloodstream into the tissue cells, where it can be used as
an important source of energy (Copstead & Banasik, 2010, p. 902). The liver and the muscles
play an important role in maintaining normoglycemic levels. The presence of insulin stimulates
the diffusion of glucose into adipose and muscle tissue and inhibits the production of glucose by
the liver (Copstead & Banasik, 2010, p. 944).
predominantly met by glucose and fats.
Energy requirements of humans are
Insulin directly affects glucose metabolism by
promoting glucose uptake by the liver, which then favors the synthesis of glycogen. Under the
influence of insulin, glucose is stored by the liver and muscle cells as glycogen; fat tissue is
deposited; and muscle tissue is built (Copstead & Banasik, 2010, p. 902).
Glucagon is
synthesized in the alpha cells of the pancreas in response to low plasma glucose concentration
(Casey, 2011, p. 16). During a fasting state, when glucose levels are lower in the body, the liver
and muscles normally respond by the process of glucogenolysis (breakdown of stored glycogen)
and glyconeogenesis (production of glucose from amino acids and other substrates) in the liver
(Copstead & Banasik, 2010, p. 944).
In diabetes mellitus, type 2, these normal processes to
maintain normoglycemia are adversely affected. The body is not able to compensate properly.
There is impaired glucose uptake due to inadequate compensation of insulin secretion for insulin
resistance (Sarampudi et al., 2009, p. 221). Studies show that glyconeogenesis is increased in
DIABETES MELLITUS TYPE 2
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type 2 diabetes mellitus with fasting hyperglycemia. The presence of inappropriate glucagon
secretion (due to suppression of glucagon) appear to contribute to elevated plasma glucose levels
in type 2 diabetes mellitus (Sarampudi et al., 2009, p. 222).
Hormones released from the gastrointestinal tract also play a significant role in
maintaining normoglycemia. This incretin effect occurs when the gut releases hormones called
glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) to
trigger insulin release when glucose rises after eating a meal. GLP-1 delays gastric emptying,
inhibits glucagon production, and increases satiety (Copstead & Banasik, 2010, p. 943).
Surampudi, et al. (2009) further explain the incretin effect:
The beta cell secretion of insulin is greater after the oral administration of glucose than
after the intravenous administration of glucose in normal glucose tolerance subjects. This
difference in insulin secretion is called the incretin effect.
Normally, incretins are
reduced in the fasting state and increase rapidly after a meal. In the presence of impaired
glucose tolerance and diabetes mellitus type 2, the incretin effect is affected adversely.
There appears to be a reduction in the nutrient mediated secretion and variation in the
level or action of GIP and GLP-1 after the ingestion of a mixed meal. The decrease in
the effective action of incretins in type 2 diabetes mellitus may help contribute to
decreased beta cell mass and insulin secretion (Surampudi, et al., 2009, p. 220).
The progressive loss of beta cell function and increased insulin resistance may be due to a
number of factors such as genetic abnormalities and acquired defects. Although a degree of
insulin resistance may be inherited, it may progress with additional factors such as obesity and a
sedentary lifestyle (Sarampudi, et at., 2009, p. 217). Abdominal fat acts as an endocrine organ,
releasing hormones and a variety of inflammatory mediators (adipokines) that affect lipid
DIABETES MELLITUS TYPE 2
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metabolism and directly impact on insulin resistance and hyperglycemia through lipotoxicity
(Casey, 2011, p. 19).
Chronic hyperglycemia in type 2 diabetes mellitus can lead to multisystem organ
damage. Casey, 2011, reviews long term complications of type 2 diabetes mellitus can be
microvascular or macrovascular:
Macrovascular complications include stoke, cardiovascular disease and peripheral
vascular disease, and are the major cause of mortality for people with type 2 diabetes
mellitus.
Microvascular
complications
encompass
neuropathies,
nephropathy,
retinopathy, and encephalopathies. Early detection and treatment of complications of
type 2 diabetes mellitus are essential for quality of life and cost reasons (Casey, 2010, p.
20).
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References
Casey, G. (2011). The sugar disease -- understanding type 2 diabetes mellitus. Kai Tiaki
Nursing New Zealand, 17(2), 16-21.
Copstead, L. E., & Banasik, J. L. (2010). Diabetes Mellitus. Pathophysiology (4th ed., pp. 902953). St. Louis, Mo.: Saunders Elsevier.
Diabetes Statistics - American Diabetes Association. (n.d.). American Diabetes Association
Home Page - American Diabetes Association. Retrieved August 7, 2012, from
http://www.diabetes.org/diabetes-basics/diabetes-statistics/
Hicks, D. (2010).
Self-management skills for people with type 2 diabetes.
Nursing
Standard, 25(6), 48-56.
Surampudi, P. N., John-Kalarickal, J., & Fonseca, V. A. (2009). Emerging Concepts in The
Pathophysiology of Type 2 Diabetes Mellitus. Mount Sinai Journal of Medicine, 76(3),
216-226. doi:10.1002/msj.20113
Strayer, D., & Schub, T (2011). Diabetes Mellitus, Type 2