With the information provided in the case study the patient with the new diagnosis of

type 2 diabetes had the often accompanied other conditions hypertension, high (LDL)
cholesterol, and low (HDL) cholesterol that increase cardiovascular risk. These
comorbidities are referred to as the metabolic syndrome. In explalining to the patient
about the disease process the nurse practitioner will have a knowledge base of type 2
diabetes.
Type 2 diabetes is a metabolic disorder that is characterized by
hyperglycemia (high blood sugar) in the context of insulin resistance and
relative lack of insulin. "Insulin resistance may be the best predictor of type
2 diabetes (McCulloch & Robertson, 2014)." Therre is also the
predominance of genetic risk, aging, and weight gain as other factors that
increase the risk for type 2 diabetes. The risk for African Americans,
Hispanic Americans in the USA have a increased risk for this disease of up
to six time that of the caucasian or white american. If there is familial
relatives such as parents that have the disease then the risk is up to ten times
higher.
With diabetes type 2 insulin resistance may be seen years prior to the onset
of hyperglycemia. Hyperglycemia itself may contribute to the disease
progression by a possible toxic effect on beta cells of the pancreas. Insulin
first binds to insulin receptors that are throughout the body and this causes a
response in the body that is mediated by the receptor substrates. With insulin
resistance the cells are do not respond normally to the levels of insulin,
which occurs in the fat tissue, muscles, and liver. The liver is usually the site
where insulin stops or decreases the release of glucose.
proportion of insulin resistance versus beta cell dysfunction differs among
individuals, with some having primarily insulin resistance and only a minor
defect in insulin secretion and others with slight insulin resistance and
primarily a lack of insulin secretion.[3]
Other potentially important mechanisms associated with type 2 diabetes and
insulin resistance include: increased breakdown of lipids within fat cells,
resistance to and lack of incretin, high glucagon levels in the blood,
increased retention of salt and water by the kidneys, and inappropriate
regulation of metabolism by the central nervous system.[4] However, not all
people with insulin resistance develop diabetes, since an impairment of
insulin secretion by pancreatic beta cells is also required.[3]

Obesity, for example, causes peripheral resistance to insulin-mediated glucose uptake

[9,89,90] and may also decrease the sensitivity of the beta-cells to glucose

The mechanism by which obesity induces insulin resistance is poorly understood. The
pattern of fat distribution and perhaps a genetic abnormality in the beta-3-adrenergic
receptor, as described above, appear to contribute. The c-Jun amino-terminal kinase
(JNK) pathway may be an important mediator of the relationship between obesity and
insulin resistance as JNK activity is increased in obesity, an effect that can interfere with
insulin action. In animal models of obesity, absence of JNK1 results in decreased
adiposity and enhanced insulin sensitivity
Plasma free fatty acid (FFA) concentrations are high in obese patients. A high plasma
FFA concentration is a risk factor for type 2 diabetes (relative risk 2.3) [101], may inhibit
insulin secretion and can inhibit insulin-stimulated glucose uptake in patients with type 2
diabetes
A large number of drugs can impair glucose tolerance; they act by decreasing insulin
secretion, increasing hepatic glucose production, or causing resistance to the action of
insulin (table 2). Included in this list are glucocorticoids, oral contraceptives, several
classes of antihypertensive drugs such as beta blockers, thiazide diuretics, nicotinic acid,
statins, protease inhibitors used for the treatment of HIV infection, gonadotropin
releasing hormone agonists used for the treatment of prostate cancer, tacrolimus,
sirolimus, and cyclosporine used primarily to prevent transplant rejection, and some of
the atypical antipsychotic agents
Thiazide diuretics Treatment with thiazide diuretics is associated with an increase in
fasting plasma glucose (FPG) and risk of developing type 2 diabetes [157,158]. However,
a substantial increase in FPG is unusual, even in patients with type 2 diabetes, with the
currently recommended regimen of low-dose thiazide therapy (eg, 12.5 to a maximum of
25 mg of hydrochlorothiazide) (figure 8) [159-161]. Concurrent hypokalemia appears to
play an important role, as evidenced by a small study showing no change in glucose
tolerance if urinary losses are replaced by potassium supplements [162]. Subsequent
analyses of larger trials confirmed the association between hypokalemia and a higher
probability of developing type 2 diabetes [163,164]. As an example, in the Systolic

Hypertension in Elderly Program trial, the risk of diabetes with use of a thiazide
(chlorthalidone) was significantly attenuated when adjusted for changes in serum
potassium [163]. Each 0.5 mEq/L decrease in serum potassium was associated with a 45
percent higher risk of new diabetes. The putative mechanism for this association is a
failure of potassium channels to close in response to rising plasma glucose
concentrations, with a resultant decrease in insulin secretion. (See "Treatment of
hypertension in patients with diabetes mellitus".)
Antipsychotics In patients with preexisting diabetes, the initiation of atypical or
typical antipsychotic agents has been associated with worsening hyperglycemia [165]. In
addition, some of the atypical antipsychotic agents, in particular, clozapine and
olanzapine, have been associated with weight gain, obesity, hypertriglyceridemia, and
development of diabetes mellitus [166-168]. The mechanism(s) by which they cause the
metabolic syndrome have not been defined. An American Diabetes Association consensus
panel concluded that data on risperidone and quetiapine show an increased risk for
weight gain, but conflicting data on diabetes and dyslipidemia risk [169]. The panel also
concluded that patients taking ziprasidone and aripiprazole are not at increased risk for
developing diabetes or dyslipidemia
Type 2 diabetes mellitus is caused by a combination of varying degrees of insulin
resistance and relative insulin deficiency. Its occurrence most likely represents a complex
interaction among many genes and environmental factors, which are different among
different populations and individuals. (See 'Pathophysiology' above.)
The search for plausible candidate genes has focused upon genes coding for proteins
that might be involved in pancreatic development, insulin synthesis, secretion, or action.
(See 'Genetic susceptibility' above.)
The most striking environmental risk factors in most patients who develop type 2
diabetes are increased weight gain and decreased physical activity, each of which
increases the risk of diabetes. (See 'Role of diet, obesity, and inflammation' above.)
The mechanism by which obesity induces insulin resistance is poorly understood.
Inflammation may be the common mediator linking obesity to the pathogenesis of
diabetes. (See 'Role of diet, obesity, and inflammation' above.)
A large number of drugs can impair glucose tolerance. They act by decreasing insulin
secretion, increasing hepatic glucose production, or causing resistance to the action of
insulin (table 2). (See 'Drug-induced hyperglycemia' above.)