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Correlation Between Obesity, Diabetes Mellitus 2, and Coronary Artery Disease

Viktoriia S. Kafando

School of Nursing, James Madison University

NSG 461: Pathophysiology and Pharmacology

Prof. Joan Timalonis

April 11, 2021

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Correlation Between Obesity, Diabetes Mellitus 2, and Coronary Artery Disease

According to McCance and Heuther (2019), 1/3 of children and 2/3 of adults in the

United States are obese and obesity is on the rise (p. 1077). Obesity is the fifth leading cause of

death in the United States, which is associated with cardiovascular disease and diabetes mellitus

2 (DM2). Obesity causes dyslipidemia, which in turn causes insulin resistance and predisposes

obese individuals to DM2 (McCance & Heuther, 2019, pp. 715-716). Diabetes causes multiple

organ damage; coronary artery disease (CAD) causes occlusion to coronary arteries and both can

cause disability and death. Insulin resistance along with dyslipidemia are risk factors for CAD

(McCance & Heuther, 2019, p. 1077). This paper provides an overview of pathophysiologic

processes, pharmacotherapeutic treatment, and nursing involvement of three common,

interrelated diseases: obesity, DM2, and CAD.

Disease Information

Obesity is characterized by accumulation of fat cells, adipocytes, which alter body’s

normal metabolic functions due to dyslipidemia, and lead to insulin resistance, which in turn is a

high-risk factor for CAD an DM2 (McCance & Heuther, 2019, pp. 715-717). DM2 affects 9.3%

of adults in the United States and is a growing problem among children (McCance & Heuther,

2019, p. 688). This endocrine disorder causes insulin resistance and deficiency, and can cause

multiorgan complication like cardiovascular disease, neuropathy, retinopathy, nephropathy, and

increased mortality (McCance & Heuther, 2019, p. 688). CAD is characterized by formation of

atherosclerotic plaques that diminish blood supply to the coronary arteries, fatal infarction occurs

if artery becomes occluded (McCance & Heuther, 2019, p. 1074).

Pathophysiology
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Obesity has a complicated pathophysiology and includes interaction of peripheral and

central pathways, adipokines, hormones, and neurotransmitters. Adipocytes, mostly white cells,

are responsible for obesity, and these cells secrete adipokines and store triglycerides when their

quantity in the periphery increased (McCance & Heuther, 2019, p. 716). Adipokines along with

other hormones responsible for intake of food regulation, energy metabolism, and their

imbalances that are seen with obesity causes dysfunction of these processes. A high level of

leptin (produced by adipocytes) is ineffective in suppressing hunger, causes hyperglycemia,

hyperlipidemia, produces proinflammatory mediators, which causes insulin resistance, and leads

to atherosclerosis (McCance & Heuther, 2019, p. 716). In individuals with visceral obesity, a

decreased level of adiponectin decreases insulin sensitization, hepatic gluconeogenesis, muscle

glucose uptake, and promotes inflammation (McCance & Heuther, 2019, p. 717).

Multiple organs contribute to insulin resistance, which is associated with obesity. Obesity

is one of the major factors that causes insulin resistance because adipose tissue causes an

elevated level of leptin, a decreased level of adiponectin, and inflammation, which decrease

insulin synthesis and resistance (McCance & Heuther, 2019, p. 688). Adipocytes create elevated

levels of free fatty acids, triglycerides, and cholesterol, which promote inflammation and

decrease tissue response to insulin and cause apoptosis of beta cells. Inflammatory cytokines

alter oxidative phosphorylation in cellular mitochondria and therefore promote insulin resistance,

which leads to fatty liver, atherosclerosis, dyslipidemia, hyperinsulinemia, and impaired insulin

receptor signaling (McCance & Heuther, 2019, p. 688). Elevated blood glucose levels cause

polyuria, polydipsia, fatigue, neuropathy, and lead to diseases of cardiovascular system

(McCance & Heuther, 2019, p. 689).

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CAD is linked to dyslipidemia and insulin resistance. A diet high in fats and cholesterol

results in increased serum levels of low-density lipoproteins (LDLs), which leads to hepatic

dysfunction of LDL receptors, and as a result high level of LDLs in bloodstream. LDLs

migration and oxidation into the vessel wall and accumulation of macrophages cause

atherosclerosis (McCance & Heuther, 2019, p. 1075). High-density lipoproteins (HDLs) are

responsible for removing excess cholesterol, protecting LDLs from oxidation, and they have

anti-inflammatory and anti-thrombotic properties. HDLs preserve endothelial function, and low

level of HDL promotes formation of plaques, which can partially or completely block blood

supply to the heart (McCance & Heuther, 2019, p. 1077). Insulin resistance on the other hand

cause endothelial damage, thickening of the vessel walls, increased inflammation, and

thrombosis, as a result formation of atherosclerotic plaques occurs (McCance & Heuther, 2019,

p. 1077). Obesity changes adipokines (a group of hormones released by adipose cells) and

increases risk of deposition at the perivascular adipose tissue which leads to atherogenesis

(McCance & Heuther, 2019, p. 1077).

Overall, obese individuals are at increased risks for metabolic dysregulation, insulin

resistance, inflammatory cytokines secretion, cardiovascular disease, other complications, and

higher mortality (McCance & Heuther, 2019, pp. 718-719).

Analysis of Cellular Event and Systemic Effects of Obesity, DM2, and CAD

In obesity, adipokines and other hormones disbalance contribute to inflammation and

insulin resistance, which leads to DM2, as well as cardiovascular disease. Obesity causes a lower

level of adiponectin, which associated with increased risk for CAD that triggered by

hypertension, hyperlipidemia, thrombotic and inflammatory factors and promotes plaques

formation (McCance & Heuther, 2019, p. 717). Angiotensinogen increased in obese individual
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and promotes lipogenesis, inflammation, oxidative stress which contribute to atherosclerosis,

DM2, hypertension, and cancer (McCance & Heuther, 2019, p. 718). Disbalance of hormones

decreases peoples’ satiety, which contributes to further excessive food intake.

According to McCance and Heuther (2019), obesity is a major reason for insulin

resistance and therefore DM2 because of metabolic dysfunction and dyslipidemia caused by fat

cells (p. 688). Increased levels of leptin, angiotensinogen, triglycerides, and cholesterol along

with decreased levels of adiponectin, and ongoing release of inflammatory cytokines decrease

tissue response to insulin, and cause apoptosis of beta-cells (McCance & Heuther, 2019, p. 688).

Elevated glucose levels result in recurrent infections (glucose stimulates growth of

microorganisms, impairs healing from decreased blood supply, and weakens immune response);

paresthesia; pruritus; visual changes; and fatigue (impaired food metabolism because of

metabolic dysfunction) (McCance & Heuther, 2019, p. 690).

Diabetes and obesity result in dyslipidemia which increases risk of CAD (McCance &

Heuther, 2019, p. 1075). Insulin resistance and hyperglycemia not only cause dyslipidemia, but

also can damage cardiovascular system by damaging endothelia lining, thicken vessel wall,

increase inflammation and thrombosis (McCance & Heuther, 2019, p. 1077). Abdominal obesity

is the strongest link with CAD, due to insulin resistance, decreased HDL levels, hypertension,

and inflammation. Obesity cause changes in adipokines and deposition of adipose tissue in

vascular system and causes atherogenesis and formation of plaques that can occlude blood

supply to the coronary arteries (McCance & Heuther, 2019, p. 1077).

Treatment of the Disease

Pharmacologic Treatment
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Some of the drugs, like Orlistat, are approved for treatment of obesity. According to

DynaMed (2018e), lipase inhibitors bind with gastric and pancreatic lipases and unable to absorb

triglycerides, results in calorie deficit and weight loss. Recommended dose of Orlistat is 120 mg

orally 3 times daily during or within 1 hour of each fat-containing meal. Common side effects of

lipase inhibitors are nausea, vomiting, hemorrhoids allergic reactions, and elevated liver

enzymes. Patient education would include reporting right upper quadrant pain, dark urine,

yellowish of skin and eyes (hepatic failure), wait four hours before and after taking

Levothyroxine, and use fat-soluble vitamins at least two hours before or after lipase inhibitors

(DynaMed, 2018e).

There are oral and subcutaneous hypoglycemic medications available for treatment of

diabetes. Metformin is the most used oral medication to treat DM2. Metformin is an oral

hypoglycemic, antidiabetic medication, which belongs to a class of biguanides. It decreases

hepatic production and intestinal absorption of glucose, lowers basal and postprandial plasma

glucose, and increases peripheral glucose intake by stimulating intracellular synthesis of the

glycogen. Metformin increases the transport capacity of all types of glucose membrane

transporters (DynaMed, 2018c). The common dose is 500mg twice a day. Common side effects

of biguanides include diarrhea, indigestion, nausea, headache, vomiting, flatulence, asthenia,

abdominal pain, sweating, and rash. Kidney function evaluation is important with Metformin

administration. Patient education will focus on reporting symptoms of lactic acidosis (abdominal

discomfort, diarrhea, muscle pain, weakness); renal failure (decreased urine production, malaise,

loss of appetite, high blood pressure); avoidance of excessive alcohol use; symptoms and

treatments of hypoglycemia (DynaMed, 2018c).

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Statin treatment is recommended for CAD for individuals 21 and older. It helps to reduce

mortality and myocardial infarction (DynaMed, 2018f). Some of the most common medications

are Simvastatin and Atorvastatin, which belong to the HMG-COA reductase inhibitor drug

classification, usually taken once daily. Statins inhibit cholesterol synthesis in the liver and lower

blood level of cholesterol; increase in LDLs receptors mediate the reduction in serum LDL

cholesterol concentration (DynaMed, 2018f). Side effects of statins include headache,

constipation, nausea, abdominal pain, insomnia, vertigo, and respiratory infections. Patients

should be taught to report symptoms of myopathy, rhabdomyolysis, especially when

accompanied by fever or malaise, notify of any signs of liver injury. Patients should be instructed

to take medication on empty stomach at night and avoid grapefruit juice (DynaMed, 2018f).

The Treatment of Pathophysiologic Mechanism Shared by These Diseases

One of the key interventions is to prevent and treat obesity and therefore adipose tissue

accumulation, whose cells secrete a variety of hormones which leads to dyslipidemia and insulin

resistance. Lowering levels of LDLs and cholesterol help to manage dyslipidemia and can lower

incidents of CAD and insulin resistance. In individuals with DM2, treatment of insulin resistance

is important to prevent damage to arteries and other organs. Treatment of insulin resistance and

dyslipidemia can help prevent CAD. McCance and Heuther (2019) state that “Obesity is the

most important contributors to insulin resistance and diabetes…” (p. 688). The authors also

mention that abdominal obesity has the strongest association to CAD and insulin resistance

(McCance & Heuther, 2019, p. 1077).

Role of the Nurse

Education about obesity and its complications is critical. Nurses should discuss lifestyle

changes with obese and overweight patients, diet and exercise are the most of importance
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(DynaMed, 2018d). A dietician consult can be helpful to choose proper meal planning that may

help to lose weight and decrease intake of saturated fats. Multidisciplinary team involvement

may be needed if patients have developed complications or other diseases. Psychotherapy,

behavioral interventions, self-motivation, support groups, drugs, or surgeries can be optional

treatments (McCance & Heuther, 2019, p. 1719). Some people may not see themselves as obese

or may feel persuaded. Before educating patients, nurses should first assess how patients feel

about their condition to make sure they are comfortable discussing it.

Nurses’ role in management of DM2 is focused on prevention of complications by

lowering glucose to desirable levels. Diet modification, exercise, medications proper use and

evaluation of medication regimen should be discussed in detail. Treatment of hypertension,

dyslipidemia, and weight management should be addressed with a personalized treatment plan.

An eye exam, and kidney function test should be completed regularly to screen for retinopathy

and assess kidney failure; routine screening for psychosocial problems and cardiovascular

disease should be performed annually (DynaMed, 2018b). Education and evaluation about

medication regimen is important to prevent further complications. Education about signs,

symptoms, and treatments of hypoglycemia, and symptoms of diabetic ketoacidosis (DKA) is

important for diabetic patients to prevent possible deaths.

Like with obesity and DM2, nurses’ role is important to educate patients about risk

factors and complications of CAD; exercise regimen, diet with limited saturated fat, trans fats,

increased fruits and vegetables, blood pressure control, smoking cessation, and limited alcohol

intake should be emphasized (DynaMed, 2018a). Management of diabetes for diabetic patients

should be included. Proper use of medications and their side effects should be discussed. Nurses

should instruct patient to seek care if worsening of cardiovascular system occurs.

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Nurses should be aware of cultural differences when teaching patients, and age, gender,

and ethnicity should be considered for patients’ better understanding and outcome. Language and

educational barriers may exist, so nurses first must assess patients’ understanding of language

and material. Religion and ethnicity may alter education and interventions proposed by the nurse,

so nurses must be culturally sensitive. If patients have biases about nurse’s ethnicity,

involvement of multicultural team members may be beneficial for patients’ outcome.

Conclusion

Obesity, DM2, and CAD are interrelated and on the rise in the US. Obesity with its

complications, like DM2 and CAD, is a leading cause of death. Obesity alters metabolic state of

the body, and this dysregulation of many hormones leads to increased risks for DM2 and CAD.

Dyslipidemia further causes insulin resistance which speeds up the progression of CAD. All

these conditions develop over years; however, they cause multiple organ damage, and failure.

Weight loss, prevention, and management of obesity are the main factors to reduce DM2 and

CAD. Likewise, proper management of insulin resistance and dyslipidemia lowers risk of CAD.

Nurses’ involvement is important in education about diseases, its complications, management,

and involvement of interdisciplinary team. Nurses should be culturally competent when caring

for patients.
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References

DynaMed. (2018a). Coronary artery disease (CAD). DynaMed.

https://www.dynamed.com/condition/coronary-artery-disease-cad

DynaMed. (2018b). Diabetes mellitus type 2 in adults. DynaMed.

https://www.dynamed.com/condition/diabetes-mellitus-type-2-in-adults

DynaMed. (2018c). Metformin. DynaMed.

https://www.dynamed.com/drug-monograph/metformin

DynaMed. (2018d). Obesity in adults. DynaMed.

https://www.dynamed.com/condition/obesity-in-adults

DynaMed. (2018e). Orlistat. DynaMed.

https://www.dynamed.com/drug-monograph/orlistat#GUID-2EA99F0B-21FB-4B2A-

881B-706808129193

DynaMed. (2018f). Simvastatin. DynaMed.

https://www.dynamed.com/drug-monograph/simvastatin#GUID-2EA99F0B-21FB-

4B2A-881B-706808129193

McCance, K. L., & Heuther, S. E. (2019). Pathophysiology: The biologic basis for disease in

adults and children (8th ed.). Elsevier, Inc.