|
| A) | 12 million | ||
| B) | 20.4 million | ||
| C) | 23.6 million | ||
| D) | 37.3 million |
Diabetes, known clinically as diabetes mellitus, is a progressive disease process affecting the fuel metabolism functioning within the body [3]. According to the Centers for Disease Control and Prevention (CDC), the prevalence of diagnosed diabetes has increased from less than 1% of the U.S. population in 1958 to 7.4% in 2015 [4]. As of 2019, 11.3% of the U.S. population, or 37.3 million Americans, have diabetes. Unfortunately, 8.5 million of these individuals are unaware of their diabetes diagnosis [5,6]. Diabetes has been considered epidemic since the 1970s, and the percentage of Americans expected to have diabetes or impaired glucose tolerance (IGT) is estimated to reach 15% to 20% by the year 2025 [7].
| A) | White Americans | ||
| B) | Non-Hispanic Black Americans | ||
| C) | Hispanic Americans | ||
| D) | Native American/Alaskan Natives |
The scope of the problem is vast and diverse. From 1994 through 2015, the prevalence of diagnosed diabetes increased across all states. In 1994, only one state had a prevalence greater than 6.0%. In 2018, all states had prevalences greater than 6.0%, and 35 exceeded 9.0% [8]. According to data from the Behavioral Risk Factor Surveillance System, West Virginia has the highest rate of adults with diabetes (13.4%). Eight of the 10 states with the highest rates (12% to 12.9%) are in the South. Colorado ranked last at 6.6% [8]. Genetics, race, age, and lifestyle influence the onset and progression of the disease process significantly [9]. According to the 2022 National Diabetes Statistics Report, the percentage of adults with diagnosed diabetes was highest among American Indians/Alaska Natives (14.5%), non-Hispanic Black Americans (12.1%), and people of Hispanic origin (11.8%), followed by non-Hispanic Asians (9.5%) and non-Hispanic White Americans (7.4%) [10]. Native Americans/Alaskan Natives present the greatest risk for the development of type 2 diabetes; their risk is more than two times greater than that of White Americans. Among Native American subgroups, the rate of diabetes among Alaska Natives is 6.0%, while Native Americans in Southern Arizona have rates of 22% [6].
| A) | 10% | ||
| B) | 40% | ||
| C) | 60% | ||
| D) | 90% |
In the case of type 1 diabetes, pancreatic beta cells fail to produce and release insulin, and the only treatment option is exogenous insulin and other appropriate injectables [7]. However, the pathogenesis of type 2 diabetes is more complex. Virtually all individuals diagnosed with type 2 diabetes have insulin resistance in conjunction with some degree of insulin deficiency [14]. In response, the body's inability to react to the mounting glucose level is magnified by insulin deficiency in the functioning pancreatic beta cells, insulin resistance in the muscular tissue, or both [3]. Unlike the therapy for type 1 diabetes, type 2 diabetes is initially treated with lifestyle modification therapy (e.g., medical nutrition therapy, exercise, behavior change) and frequently with an oral medication, such as a biguanide. Within five years of type 2 diabetes diagnosis, it is estimated that as many as 90% of people will fail this initial therapy and require further oral medications or injectables to achieve adequate glucose control. As a result of this failure rate, medication therapy is initiated early (in the prediabetes stage) in diabetes medical treatment algorithms [15].
| A) | 3 | ||
| B) | 4 | ||
| C) | 5 | ||
| D) | 6 |
The concentration of plasma glucose is dependent on the rate glucose enters the circulation in contrast to the rate it is removed [17]. Fuel homeostasis within the body can be explained in a five-phase approach [18]. Phase 1, or the fed state, occurs immediately and up to 3.9 hours after consumption of food. During this phase, the circulating glucose is predominantly from an exogenous source. Plasma insulin levels are elevated, glucagon levels are minimal, and triglycerides are synthesized in the liver. Insulin impedes the breakdown of glycogen and triglyceride reservoirs. The brain and other glucose-dependent organs utilize some of the glucose absorbed from the intestinal tract, and the excess glucose is stored in the liver, muscle, adipose tissue, and other tissues for use later.
| A) | Phase 2 | ||
| B) | Phase 3 | ||
| C) | Phase 4 | ||
| D) | Phase 5 |
Phase 3 is the early starvation state. About 16 to 47.9 hours after the consumption of food, the blood glucose is generated from hepatic gluconeogenesis and glycogenolysis. Gluconeogenesis continues to generate most of the hepatic glucose. In this phase of starvation, lactate makes up half of the gluconeogenesis substrate along with amino acids (specifically alanine) and glycerol. The secretion of insulin is suppressed, and counter-regulatory hormone (i.e., glucagon, cortisol, growth hormone, epinephrine) secretion is stimulated.
| A) | 0 to 3.9 hours after consumption of food. | ||
| B) | 4 to 15.9 hours after consumption of food. | ||
| C) | 16 to 47.9 hours after consumption of food. | ||
| D) | 48 hours to 23 days after consumption of food. |
Phase 4 begins 48 hours to 23 days after food consumption. During this preliminary prolonged starvation state, blood glucose originates from hepatic and renal gluconeogenesis. Within 60 hours of starvation, gluconeogenesis provides more than 97% of hepatic glucose output. The secretion of insulin is distinctly diminished and counter-regulatory hormone secretion is stimulated.
| A) | Renal | ||
| B) | Cardiac | ||
| C) | Microvascular | ||
| D) | Macrovascular |
Research from the DCCT trial was further substantiated in the United Kingdom Prospective Diabetes Study (UKPDS), a clinical trial of patients with newly diagnosed type 2 diabetes conducted between 1977 and 1997. Once more, the groups were separated into a conventional therapy study arm or an intensive therapy arm to determine the efficacy and outcomes of the differing treatments [14]. Intensive blood glucose control was achieved utilizing sulfonylurea medications or insulin in normal-weight people and metformin in participants who were overweight. The UKPDS aimed to treat patients using only a single medication even if blood glucose became quite high because, at the time, there were some concerns that utilizing multiple medications had the potential of being harmful. In the conventional therapy cohort, lifestyle alone was used to control blood glucose. This was the first study to establish the now well-known association between level of glucose control and the reduction of microvascular complications (i.e., retinopathy, nephropathy, neuropathy) in individuals with type 2 diabetes [26].
| A) | Asian race | ||
| B) | Hypertension | ||
| C) | Age younger than 30 years | ||
| D) | Body mass index greater than 18 kg/m2 |
Criteria for screening for diabetes or prediabetes in asymptomatic adults include [35]:
Testing should be considered in adults with overweight or obesity (body mass index [BMI] ≥25 kg/m2 [≥23 kg/m2 in Asian Americans]) who have one or more of the following risk factors:
First-degree relative with diabetes
High-risk race/ethnicity (e.g., African American, Hispanic American, Native American, Alaskan Native, Pacific Islander, Asian American)
History of CVD
Hypertension (blood pressure ≥140/90 mm Hg or on therapy for hypertension)
HDL cholesterol level <35 mg/dL and/or a triglyceride level >250 mg/dL
Women with polycystic ovarian syndrome
Physical inactivity
Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)
Patients with prediabetes (A1c ≥5.7%, IGT, or IFG) should be tested yearly.
Women who were diagnosed with gestational diabetes should have lifelong testing at least every three years.
For all other patients, testing should begin at 35 years of age.
If results are normal, testing should be repeated as a minimum of three-year intervals, with consideration of more frequent testing depending on initial results and risk status.
| A) | 5 mg. | ||
| B) | 10 mg. | ||
| C) | 20 mg. | ||
| D) | 40 mg. |
Historically, there were few options to achieve control of blood glucose levels, and pharmacologic management was limited to the sulfonylureas [3]. Today, sulfonylurea medications are categorized as either first- or second-generation (Table 2). These medications are typically used as primary or secondary agents in the treatment of type 2 diabetes. Sulfonylureas can be rapid-acting, intermediate-acting, or long-acting based on their onset and duration of action. For sulfonylureas to be effective, the individual must have functioning pancreatic beta cells. Thus, they are not useful for patients with type 1 diabetes [40]. Some individuals will not respond to initial sulfonylurea therapy, and over time, most will experience failure with this therapy as the disease progresses. The ideal candidate for sulfonylurea therapy is a patient with [41]:
Type 2 diabetes without dyslipidemia
Normal weight
Hyperglycemia despite following meal planning and an exercise program
Ability and willingness to follow a reasonable dietary program
Hyperglycemia for less than five years
Age older than 30 years
| A) | Weight gain | ||
| B) | Liver failure | ||
| C) | Hypoglycemia | ||
| D) | Gastrointestinal disturbances |
As with any drug therapy, a hypersensitivity reaction can potentially occur with sulfonylurea therapy. However, hypersensitivity to one agent does not necessarily indicate a cross-sensitivity with other sulfonamide agents. Care should be taken when treating geriatric, malnourished, or debilitated patients, as these groups are at particular risk for hypoglycemia. Furthermore, any person with adrenal, pituitary, or hepatic insufficiency who is particularly susceptible to the hypoglycemic effects of glucose-lowering agents should be closely monitored while on a sulfonylurea therapy regimen [3]. Alteration in hepatic enzyme activity may also alter the clearance of sulfonylurea agents.
A secondary side effect of sulfonylurea therapy is weight gain as a result of a greater amount of circulating insulin [42]. This increase results in a greater amount of circulating glucose being stored as adipose tissue. Less commonly seen sulfonylurea side effects include [42]:
Skin rash (2%)
Gastrointestinal disturbances (5%)
Metabolic disorders (e.g., syndrome of inappropriate antidiuretic hormone hypersecretion associated with chlorpropamide use) (4%)
| A) | 20 mg. | ||
| B) | 40 mg. | ||
| C) | 360 mg. | ||
| D) | 2,550 mg. |
NONSULFONYLUREA SECRETAGOGUES (GLINIDES)
| Drug Name | Trade Name | Dose Range | Maximum Daily Dose | Frequency | Onset of Action | Duration of Action |
|---|---|---|---|---|---|---|
| Repaglinide | Prandin (discontinued in the United States) | 0.5–4.0 mg before meals | 16 mg | Up to four times daily | 25 to 30 minutes | 4 to 6 hours |
| Nateglinide | Starlix | 60–120 mg before meals | 360 mg | Three times daily | Within 20 minutes | 4 hours |
| A) | 100 mg. | ||
| B) | 300 mg. | ||
| C) | 1,000 mg. | ||
| D) | 2,550 mg. |
| A) | Diarrhea | ||
| B) | Flatulence | ||
| C) | Dry mouth | ||
| D) | Abdominal pain |
Side effects for alpha-glucosidase inhibitors are typically confined to the gastrointestinal system and usually occur during initiation of therapy or when adjustments to the dose are made [42]. Potential side effects of alpha-glucosidase inhibitors include [42]:
Gastrointestinal effects
Abdominal pain: 12% to 21%
Diarrhea: 29% to 33%
Flatulence: 42% to 77%
Increased plasma concentration relative to the degree of renal dysfunction
Elevation in transaminases with acarbose (believed to be related to the use of higher-than-recommended dosages)
| A) | Decreases hepatic glucose production | ||
| B) | Increases beta cell production of insulin | ||
| C) | Decreases intestinal absorption of glucose | ||
| D) | Increases peripheral glucose uptake and utilization |
Metformin therapy is now frequently utilized due to the lack of hypoglycemia as a side effect [63]. If not contraindicated and if tolerated, metformin is the ADA-preferred initial pharmacologic agent for management of type 2 diabetes [35]. It is an antihyperglycemic agent that lowers both basal and postprandial plasma glucose and improves glucose tolerance. Metformin acts in several ways to achieve this effect, including inhibiting hepatic glucose production and intestinal absorption of glucose [63]. It also increases peripheral glucose uptake and utilization [42]. Unlike sulfonylureas, metformin does not increase the risk of hypoglycemia and does not cause hyperinsulinemia [64]. Insulin secretion remains unchanged using metformin, but fasting plasma insulin levels and day-long plasma insulin response may actually decrease [3].
| A) | Decreased blood pH level | ||
| B) | Serum lactate levels >5 mmol/L | ||
| C) | Blood glucose less than 40 mg/dL | ||
| D) | Electrolyte abnormality resulting in an elevated anion gap |
Biguanide therapy rarely causes serious side effects, but lactic acidosis has occurred in some cases and is an important consideration for patients taking metformin [42]. Lactic acidosis, although rare, is a potentially fatal metabolic complication. Persons at risk include those with renal insufficiency and those with acute or unstable heart failure who are at risk for hypoperfusion and hypoxemia. Characteristics of lactic acidosis include:
Serum lactate levels greater than 5 mmol/L
Decreased blood pH
Electrolyte abnormalities resulting in an elevated anion gap
Increased lactate/pyruvate ratio
| A) | 8 mg | ||
| B) | 20 mg | ||
| C) | 45 mg | ||
| D) | 100 mg |
| A) | 80 mg. | ||
| B) | 100 mg. | ||
| C) | 360 mg. | ||
| D) | 1,000 mg. |
DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS
| Drug Name | Trade Name | Dose Range | Maximum Daily Dose | Frequency | Onset of Action | Duration of Action |
|---|---|---|---|---|---|---|
| Sitagliptin | Januvia | 25–100 mg daily | 100 mg | Once daily | 1 to 4 hours | 24 hours |
| Linagliptin | Tradjenta | 5 mg daily | 5 mg | Once daily | 1.5 hours | 24 hours |
| Saxagliptin | Onglyza | 2.5–5 mg daily | 5 mg | Once daily | 2 hours | 24 hours |
| Alogliptin | Nesina | 12.5–25 mg daily | 25 mg | Once daily | — | 24 hours |
| A) | 10 to 15 minutes. | ||
| B) | 15 to 30 minutes. | ||
| C) | 60 to 90 minutes. | ||
| D) | 3 to 4 hours. |
There are two preparations of regular human insulin on the market: Humulin R and Novolin R. Both preparations are similar in action but differ in chemical make-up. Both have an onset of action of 15 to 30 minutes, and peak action is noted at 2.5 to 5 hours. The effective duration of action is between 2 to 12 hours [42]. Regular insulin can be utilized as a subcutaneous injection, intravenous infusion, insulin pump infusion, or inhaled mist, although insulin analogs are now more widely used [96,105].
| A) | Lipids | ||
| B) | Glucose | ||
| C) | Ketones | ||
| D) | Uric acid |
Diabetic ketoacidosis is caused by the body's inability to utilize glucose due to a lack of insulin. Because glucose is unavailable for energy needs, fat is used as a fuel source. The byproducts of this fat metabolism (i.e., ketones) accumulate, and electrolyte disturbances, acidosis, and severe dehydration result [109]. It occurs most often in persons with type 1 diabetes, but it can occur in patients with type 2 diabetes as well [110]. Children younger than 5 years of age and those without ready access to health care are at the greatest risk to develop diabetic ketoacidosis [111]. Factors that can precipitate the development of this disorder include [96,110,112]:
Severe infection
Serious illness, such as myocardial infarction
Inappropriate dosing or skipped or missed doses of insulin
Continuous subcutaneous insulin infusion failure
Leaving insulin pump infusion sets intact for longer than the manufacturer recommendation
Growth spurts in children and adolescents
Steroid therapy
Alcohol or illicit drug use
Stress
| A) | 150 mg/dL. | ||
| B) | 250 mg/dL. | ||
| C) | 500 mg/dL. | ||
| D) | 600 mg/dL. |
Patients experiencing HHS may present to the emergency department with seizures or symptoms that mimic a cerebrovascular accident. In most cases, physical examination will demonstrate evidence of extreme dehydration, orthostatic hypotension, and a frank hypovolemic shock. The plasma glucose level is typically greater than 600 mg/dL, with a serum osmolality level greater than 320 mOsm/kg [118]. Anything that elevates blood glucose levels or reduces hydration can contribute to the development of HHS, including [114,118]:
Infection (the precipitating factor in 60% of cases)
Surgery
Myocardial infarction
Gastrointestinal hemorrhage
Pancreatitis
Pulmonary embolism
Medications that impact carbohydrate metabolism (e.g., glucocorticoids, thiazides, phenytoin, beta blockers)
| A) | glucose therapy. | ||
| B) | insulin therapy only. | ||
| C) | antibiotic therapy only. | ||
| D) | adequate fluids to rehydrate. |
The main goal in the treatment of HHS is providing adequate fluids for rehydration [114]. Aggressive fluid replacement is crucial, as patients have an average fluid loss of 9 liters [118]. The guideline for fluid replacement is to infuse half of the fluid deficit over the initial 12 hours and the remainder during the subsequent 12 to 24 hours [114,118]. When administering hypertonic solutions, it is important to be alert to the potential of cerebral edema due to the rapid decrease in serum osmolality [118].
| A) | renal failure. | ||
| B) | heart failure. | ||
| C) | hypoglycemia. | ||
| D) | cerebral edema. |
The main goal in the treatment of HHS is providing adequate fluids for rehydration [114]. Aggressive fluid replacement is crucial, as patients have an average fluid loss of 9 liters [118]. The guideline for fluid replacement is to infuse half of the fluid deficit over the initial 12 hours and the remainder during the subsequent 12 to 24 hours [114,118]. When administering hypertonic solutions, it is important to be alert to the potential of cerebral edema due to the rapid decrease in serum osmolality [118].
| A) | Regular insulin | ||
| B) | Long-acting insulin | ||
| C) | Basal/bolus combination | ||
| D) | Continuous subcutaneous insulin infusion |
Basal insulin therapy may be administered via an injection or with a continuous subcutaneous insulin infusion. For patients with type 2 diabetes with a less than optimal blood glucose level, basal insulin may be added to oral agents to achieve the most advantageous level of metabolic control [2]. A patient's basal insulin needs can be met using a variety of preparations and routes, including intermediate-acting insulin, long-acting insulin, basal/bolus combination in multiple daily dosages, or continuous subcutaneous insulin infusions via an insulin pump.
| A) | 1 to 2 hours. | ||
| B) | 2 to 4 hours. | ||
| C) | 6 to 10 hours. | ||
| D) | 10 to 12 hours. |
NPH is available only in U100 concentration vials or pre-filled pen preparations [56]. The onset of action is within 1 to 2 hours, with peak effect to be expected within 4 to 12 hours [42]. NPH is considered an intermediate-acting insulin as its effective duration is longer than regular insulin or insulin aspart but not as long as insulin glargine or detemir [42,48]. Due to its wide variation in effective action time, this insulin may be prescribed once or twice per day [2]. As with most insulin preparations, NPH can be stored at room temperature or refrigerated until it expires or for 31 days after it is opened. As with any injectable insulin, it should be room temperature prior to injection [56].
| A) | 4 mcg twice daily. | ||
| B) | 6 mcg once daily. | ||
| C) | 10 mcg twice daily. | ||
| D) | 15 mcg once daily. |
Exenatide is available in prefilled injection pens and as a kit containing 2 mg of the drug and a diluent [56,62]. The recommended initial dosage for the pen preparation is 5 mcg twice daily within one hour prior to a meal [42]. The dose may be increased to a maximum of 10 mcg twice per day. The recommended dosage for the 2-mg kit is once every seven days (weekly); it can be administered at any time of day, with or without meals [62]. Exenatide has an onset of action of 30 minutes and effective duration of action of approximately 10 hours [48]. The greatest side effect risk and disadvantage with exenatide is nausea, which is reported by 44% of patients who take the drug [129]. Other possible side effects include vomiting, diarrhea, dizziness, headache, and dyspepsia [129]. However, the drug has the beneficial effects of beta cell rejuvenation, decreased glucagon production, and weight loss [102]. Concurrent use of insulin, metformin, sulfonylureas, or a combination of these medications with exenatide is not recommended [42]. Exenatide is best indicated for individuals who have not achieved adequate control on combination medication therapy [2].
| A) | Miglitol | ||
| B) | Sitagliptin | ||
| C) | Exenatide | ||
| D) | Pramlintide |
Like exenatide, pramlintide is another relatively new antihyperglycemic medication available to help obtain and maintain glycemic control [129]. FDA approved in 2005, pramlintide is utilized in combination with insulin therapy for patients with type 1 or type 2 diabetes [42,140]. Pramlintide mimics the human hormone amylin, a neuroendocrine hormone that contributes to glucose control during the postprandial period. As a synthetic analog of amylin, pramlintide primarily acts by promoting satiety, slowing gastric emptying, and decreasing postprandial glucagon secretion. Because use of pramlintide is associated with feelings of fullness and a reduction in caloric intake, one benefit of use is potential weight loss. Slowed gastric emptying, an effect that lasts for approximately three hours following administration, reduces the initial postprandial increase in plasma glucose, but it does not alter absorption of carbohydrates, fats, or other nutrients.
| A) | Gastroparesis | ||
| B) | Crohn disease | ||
| C) | Peptic ulcer disease | ||
| D) | Irritable bowel syndrome |
Pramlintide is contraindicated for patients with gastroparesis or who are prescribed medications that affect gastrointestinal motility or slow the absorption of nutrients [42,129]. Potential side effects include nausea, anorexia, dizziness, and pharyngitis, but the greatest risk is the development of hypoglycemia [56]. Particularly among individuals with type 1 diabetes, pramlintide taken in addition to insulin is associated with an increased risk of severe hypoglycemia [42]. When it does occur, severe hypoglycemia usually develops within three hours of administration of pramlintide injection. Complete patient education and monitoring insulin dose response can help prevent this untoward effect [141].
| A) | Dizziness | ||
| B) | Confusion | ||
| C) | Palpitations | ||
| D) | Excessive thirst |
Prevention of hypoglycemia includes not skipping meals and eating prior to exercise. Additionally, patients should be advised regarding what to do in the event of a missed medication dose. Most medication preparations should be taken as soon as the missed dose is realized, with a few exceptions. If the medication is repaglinide or nateglinide, or if it is too close to the time of the next dose, the dose should be skipped altogether [56]. Patients should also know the signs and symptoms of hypoglycemia, which include [142]:
Dizziness or lightheadedness
Weakness
Hunger
Numbness or tingling around the mouth
Headache
Palpitations
Confusion
Shakiness
Sweating
Irritability or nervousness
| A) | taking the medication whether or not the meal is eaten. | ||
| B) | signs and symptoms of liver failure, due to high potential of liver damage. | ||
| C) | signs and symptoms of impending heart failure, due to increased cardiac risks. | ||
| D) | signs and symptoms of hypoglycemia and skipping medication if a meal is skipped. |
Timing is essential for the prevention of hypoglycemia while utilizing the nonsulfonylurea secretagogues repaglinide and nateglinide. Patients should be instructed to take the medication no more than 30 minutes prior to the meal [56]. Often, patients are advised to take this medication with the first bite of a meal [3]. If a meal is not going to be consumed, the prescribed doses of the medication should also be skipped [56].
| A) | Site rotation | ||
| B) | Hypoglycemia | ||
| C) | Fluid retention | ||
| D) | Needle disposal |
Any individual initiating injectable therapy to control diabetes requires specific instructions to safely administer the medications. Necessary education related to injectable therapy includes injection techniques, site rotation, needle disposal, and identification of signs and symptoms of hypoglycemia [143].