Pathophysiology

Physiology:

The pancreas contains four types of hormone secreting cells, one of which is beta cells. Beta cells secrete both insulin and amylin. Insulin is an anabolic hormone that facilitates glucose uptake, mainly in adipose tissue, the liver, and muscle. It also increases the synthesis of carbohydrates, lipids, proteins, and nucleic acids. Overall, the primary effect of insulin is to stimulate protein and fat synthesis and decrease the blood glucose level (McCance & Huether, 2019).

Insulin secretion is regulated by hormonal, chemical, and neural control. Prior to eating a meal, the parasympathetic system stimulates the beta cells of the pancreas causing an increase in insulin secretion. At the target cell, insulin binds with enzyme-linked plasma membrane receptor cells. This insulin receptor binding creates a cascade of signals to activate glucose transporters, which allow for the entry of glucose into the cell. The primary glucose transporter is GLUT4. GLUT4 is transported to the cell surface only after the activation by the insulin receptor (McCance & Huether, 2019).

Insulin secretion may also increase with elevated blood glucose level, amino acids, and gastrointestinal hormones. Inversely, insulin secretion decreases due to hypoglycemia, increased levels of insulin, prostaglandins, and sympathetic stimulation of the beta cells (McCance & Huether, 2019).

Pathophysiology:

Both environmental and genetic influences contribute to the pathophysiology of type 2 diabetes mellitus. Metabolic syndrome places individuals at high risk for developing type 2 diabetes mellitus.  Type 2 diabetes mellitus is a metabolic disorder characterized by hyperglycemia. Many organs contribute to the chronic hyperglycemia, insulin resistance, and consequences of type 2 DM (McCance & Huether, 2019).

 

 

 

 

 

 

 

 

 

 

The hyperglycemic state is caused by defects ranging from insulin resistance in cells of the body to insulin deficiency and/or insulin secretory impairment due to defects in pancreatic beta cell function (McCance & Huether, 2019).

Insulin resistance is the impaired response of insulin sensitive tissues (especially muscle, liver, and adipose tissue), to the hormone insulin. This alteration inhibits the cell’s ability to absorb and then use glucose. Obesity is the main contributor to insulin resistance and therefore, heavily associated with type 2 diabetes mellitus (McCance & Huether, 2019).

Obesity contributes to insulin resistance and insulin deficiency through multiple different mechanisms:

-Obesity results in inflammation, increased leptin levels, and decreased adiponectin levels which all contribute to insulin resistance and decreased insulin synthesis (McCance & Huether, 2019).
-Obese individuals have high levels of serum free fatty acids and intracellular deposits of triglycerides and cholesterol. These altered levels inhibit intracellular insulin signaling, create insulin resistance, and cause apoptotic beta-cell death (McCance & Huether, 2019).
-Obesity causes the release of inflammatory cytokines that induce insulin resistance (McCance & Huether, 2019).
-Obesity causes impaired insulin receptor signaling and hyperinsulinemia. Beta cell dysfunction occurs after years of compensatory hyperinsulinemia. The beta cells are overworked by trying to maintain a normal blood glucose level. The beta cells are not able to secrete enough insulin by the time diabetes is diagnosed (McCance & Huether, 2019; Zaccardi et al., 2016).

Hormones associated with the gastrointestinal tract, specifically Ghrelin and incretins, impact insulin resistance and beta-cell function. Decreased levels of Ghrelin, a peptide that regulates food intake, is associated with insulin resistance. Likewise, decreased levels of incretins, a peptide class that impacts the synthesis and secretion of insulin along with protective beta cell properties, has been found in patients with type 2 diabetes mellitus (McCance & Huether, 2019).

 

 

 

 

 

 

 

 

 

 

 

Individuals usually present with vague symptoms including fatigue, pruritus, recurrent infections, neuropathy, or visual changes.   Polydipsia and polyuria may or may not be present.  Often the individual is overweight, hypertensive, hyperinsulinemic, and dyslipidemic.  In individuals who has progressive, nontreated diabetes, symptoms related to coronary artery, peripheral artery, and cerebrovascular disease may develop.  Diet and exercise are vital in the prevention of type 2 diabetes mellitus (McCance & Huether, 2019).

Diagnosis:

Any ONE of the following diagnostic criteria diagnoses a patient with diabetes mellitus type 2:

1. HbA1c greater than or equal to 6.5%
2. Fasting plasma glucose greater than or equal to 126mg/dL.
3. Two hour plasma glucose greater than or equal to 200mg/dL during an oral glucose tolerance test.
4. Random plasma glucose greater than or equal to 200mg/dL with classic symptoms of hyperglycemia (polydipsia, polyuria, polyphagia, weight loss) or hyperglycemic crisis (ketosis-prone type 2 diabetes)       (McCance & Huether, 2019)