Management of ketosis-prone type 2 diabetes mellitus
Management of ketosis-prone type 2 diabetes mellitus
Stefan Smolenski, RN, DNP, AGPCNP-BC (Clinical Instructor) & Nancy M. George, PhD, RN, FNP-BC, FAANP (Clinical Associate Professor)
Journal of the American Association of Nurse Practitioners
Diabetic ketoacidosis (DKA) has largely been considered unique to type 1 diabetes because of the absolute lack of insulin production secondary to beta-cell dysfunction. However, a relatively new diabetes subtype known as ketosis-prone type 2 diabetes mellitus (DM) may also elicit diabetic ketoacidosis. Ketosis-prone type 2 DM shares a similar pathophysiology as type 2 DM, but presents initially with signs and symptoms consistent with type 1 DM. Patients with ketosis-prone type 2 DM often present with elevated glucose levels of 500–700 mg/dl, elevated ketone levels, and elevations in hemoglobin A1C. Unlike DKA seen in type 1 DM, they do not exhibit autoantibodies to beta cells. The similarity with type 1 DM exists in their impaired insulin secretion, which, when combined with extreme insulin resistance, will lead to ketoacidosis. Despite the initial clinical presentation that resembles type 1 DM, patients may not require lifelong insulin and achieve appropriate glycemic control with oral agents. Nurse practitioners must recognize the clinical picture of ketosis-prone type 2 DM and use a multifaceted approach, encouraging dietary changes, increased physical activity, and medication adherence to build the self-management skills of the patient and ultimately decrease the long-term disease burden.
In 2009, diabetic ketoacidosis (DKA) was responsible for over 140,000 hospital admissions and that number has been steadily increasing ever since (Centers for Disease Control, 2014). Diabetic ketoacidosis can result in severe dehydration, hyperkalemia, cerebral edema, and death. Diabetic ketoacidosis has largely been considered unique to patients with type 1 diabetes because of the absolute lack of insulin production secondary to betacell dysfunction. However, a relatively new subtype known as ketosis-prone type 2 diabetes mellitus (DM) may also elicit diabetic ketoacidosis as the name implies.
Ketosis-prone type 2 DM, sometimes referred to as “Flatbush Diabetes” after a clinic in New York where it was first described, shares a similar pathophysiology as type 2 DM, but presents initially with signs and symptoms of type 1 DM (Balasubramanyam, Nalini, Hampe, & Maldonado, 2008). Patients with ketosis-prone type 2 DM often present with elevated glucose levels of 500–700 mg/dl, elevated ketone levels, and a hemoglobin A1C ranging from 12% to 14%. However, unlike the majority of DKA cases seen in type 1 DM, many patients do not exhibit autoantibodies to beta cells. The similarity with type 1 DM exists in patients with impaired insulin secretion, which, when combined with extreme insulin resistance, will lead to ketoacidosis.
Ketosis-prone type 2 DM typically presents with diabetic ketoacidosis in patients who fit neither the category of type 1 or type 2 diabetes. Further subcategorization of diabetes is necessary to identify the type and predict outcome and treatment strategies. Subcategories of diabetes may be segregated into four groups, which describe the disease process. The groups are defined by positive or negative responses to two measures. Those with the presence or absence of betacell autoantibodies are described as A+ or A2. In the second measure, patients with diabetes who experience recovery or lack of recovery of beta-cell function after treatment for DKA are defined as b+ or b2. Therefore, patients with ketosis-prone type 2 diabetes are often classified as “A2 b+” as they lack beta-cell autoantibodies and regain function of beta cells following diabetic ketoacidosis treatment (Patel et al., 2013) (see “AB classification table” Table 1).
The pathophysiology of ketosis-prone type 2 DM is multifactorial in nature, and it is likely that patients who are newly diagnosed have experienced undiagnosed insulin resistance for an extended period of time before the beta cells of the pancreas are unable to meet the demands of the body. After a certain period of time, the struggle to meet the increasing insulin demands of the body may lead to an acute failure of the beta cells (Whyte, 2015). This allows for glucose levels to soar into the 500–700 mg/dl range, subsequently yielding symptoms of polyuria, polydipsia, polyphagia, and eventually DKA.
Insulin has many actions in the body; it promotes glucose uptake and utilization by fat and muscle cells and inhibits gluconeogenesis as well as glycogenolysis. Insulin also has antilipolytic effects, preventing the breakdown and release of free fatty acids. Studies show that the insulin requirements to prevent lipolysis is roughly one-tenth the requirement for glucose utilization. It is hypothesized that this is why patients with type 2 DM rarely experience DKA. Patients maintain enough beta-cell reserve to prevent lipolysis and release of ketone bodies even though glucose utilization is being resisted, causing hyperglycemia (Puttanna & Padinjakara, 2014). Ketones are rarely seen in the blood, even during periods of extreme betacell failure, such as those leading to hyperosmolar hyperglycemic crisis. This is the principle reason that patients with type 2 DM experience hyperglycemia without the metabolic acidosis and ketone production of the type 1 DM counterpart.
Studies show that in ketosis-prone type 2 diabetes, an insulin deficiency tends to occur in response to constant hyperglycemia secondary to insulin resistance. Hyperglycemia will further limit the secretion of insulin, and some studies have even shown a reduction of insulin production at the genetic level by inhibiting transcription of insulin-producing proteins (Patel et al., 2013). Although a similar process occurs with traditional type 2 diabetes, patients with ketosis-prone type 2 DM may have a unique anomaly at the cellular level, which causes ketoacidosis in cases of severe beta-cell dysfunction. In the presence of hyperglycemia, some patients with ketosis-prone type 2 diabetes have been shown to exhibit increased lipolysis because of counter regulatory hormones such as glucagon, cortisol, and growth hormone (Spollett, 2003). Patients with ketosis-prone type 2 diabetes can also undergo accelerated catabolism of certain ketogenic amino acids as well as impaired ketone oxidation within the Krebs cycle (Patel et al., 2013). Thus, they have lost the protective mechanisms that exist in type 2 DM to prevent ketosis.
This analysis of cellular metabolism suggests that altered fatty acid catabolism in the presence of impaired insulin secretion and worsening hyperglycemia is what sets the stage for diabetic ketoacidosis in this atypical population of patients with diabetes (Patel et al., 2013). Increasing lipolysis and impaired metabolism at the level of the Krebs cycle closely mimic the physiology of diabetic ketoacidosis in patients with type 1 DM; however, small levels of insulin may still be present in patients with ketosis-prone type 2 diabetes (Canfield, 2014). Without these abnormalities in fatty acid catabolism and ketone production, patients with ketosis-prone type 2 DM would resemble a patient with more traditional type 2 DM. The cause of these metabolic anomalies is largely unknown.
Once ketosis has occurred, the clinical picture is very similar to that of type 1 diabetes. Continued inadequate levels of insulin will stimulate gluconeogenesis within the liver by breaking down glycogen, which will further increase blood glucose (BG) levels. The patient may then experience osmotic diuresis in response to the hyperglycemia and attempts at diuresis will be made, effectively eliminating ketones from the blood along with electrolytes via the urine. Clinically, the patient may be dehydrated, tachycardic, and hypotensive. Ketones will be present in the blood and urine, and the patients will be acidotic with a pH of less than 7.3. As with traditional instances of diabetic ketoacidosis, this is a medical emergency requiring plasma volume restoration, correction of acidosis and BG, and electrolyte replacement. It is also crucial at this time to assess for predisposing factors for the ketotic event, such as infection or other stressors (Canfield, 2014).
Although a targeted analysis of metabolic defects at the cellular level to assess accelerated ketone production is unrealistic in the clinical setting, patients with ketosisprone type 2 DM have other indicators in their history and physical, which may shed light on their diagnosis. Clinicians must understand that patients with ketosis-prone type 2 DM resemble the typical type 2 DM phenotypes and are often obese, suffer from metabolic syndrome, and show signs of insulin resistance. Insulin resistance may be demonstrated by an increased need for insulin beyond the patients’ weight-based insulin requirements. Familial history of type 2 DM is common and there is a high prevalence seen in males, as well as populations of Hispanic, African, and Caribbean ancestry (Steenkamp, Alexanian, & Sternthal, 2014).
Obtaining a detailed history from the patient is arguably the most important thing one can do when ketosisprone type 2 DM is suspected. As in the case with MH, patients presenting with DKA will often require hospitalization and will likely be administered exogenous insulin to maintain glycemic control. Initially, doses may be higher than anticipated with standard weight-based dosing because of insulin resistance. However, patients will require less and less exogenous insulin as they experience beta-cell recovery (Steenkamp et al., 2014). Relatively low BG levels may be recognized as the need for exogenous insulin decreases. Some patients may swing between periods of insulin deficiency followed by remission and can report subsequent swings in BG levels despite a lack of changes in insulin therapy. These failure and remission periods may last months to years and may be evident by fluctuating hemoglobin A1C percentages (Steenkamp et al., 2014).
Patients with ketosis-prone type 2 DM often have a strong family history of type 2 DM, are of African descent, and are usually overweight (Steenkamp et al., 2014). Because of the severe beta-cell dysfunction, these patients will initially require insulin to achieve glycemic control. However, once their glucose levels are controlled, patients with ketosis-prone type 2 DM may regain appropriate beta-cell function and thus do well on oral antidiabetic medications, which work to decrease insulin resistance when combined with diet and exercise. It is important for providers to recognize this subclass of type 2 diabetes because some may be reluctant to consider other pharmacological therapies other than or in addition to insulin therapy once glycemic control has been achieved.
Patients frequently report symptoms that are common in patients with type 2 DM as well. This includes polyuria, polydipsia, polyphagia, and weight loss that has been incremental in its progression. Numbness and tingling of the lower extremities along with delayed healing may be present because of neuropathy, and blurred vision may be a complaint if retinopathy is involved. Patients should also be assessed for a history of coronary artery disease, hypertension, or chronic renal failure because the risk for these conditions is increased among patients with diabetes (Khadori, 2017).
Physical and diagnostic tests
When completing a physical assessment, it is important to observe for signs of type 2 DM, insulin resistance, and end organ damage. This can include obesity, particularly central, because the prevalence of insulin resistance is higher among this type. Hypertension may be present and indicative of macrovascular arterial changes. Acanthosis nigricans may be seen as a discoloration, characterized by areas of darkened, velvety areas along skin folds, particularly evident in darker-skinned ethnic groups (Khadori, 2017). Patients may exhibit decreased sensation in the extremities if a monofilament test is performed.
Subsequently, any wounds or ulcers on the lower extremities should be investigated as diabetes may delay wound healing. Further examination of the feet may reveal dryness or muscle atrophy (Khadori, 2017).
Although no tests exist to assess for ketosis-prone type 2 DM, a diagnosis of diabetes may be confirmed with any one of the following tests according to 2017 American Diabetes Association guidelines. A hemoglobin A1C test, which assess BG levels over the previous three months, should be less than 6.5% in non-diabetic patients. Random BG tests above 200 mg/dl along with additional signs and symptoms classic for diabetes indicate a diagnosis of diabetes. This is in contrast to an eight-hour fasting BG which, when higher than 126 mg/dl on two separate occasions, indicates the presence of diabetes. A 2-hour 75 gram glucose tolerance test may also be performed if any of the previous tests are inconclusive or unavailable (Cefalu, 2017).
Goal of management
In many patients with diabetes, the primary goal of therapy is to reduce the A1C to below 7.0% and the subsequent risk of end organ damage while minimizing episodes of hypoglycemia. Factors such as the patient’s age, ability to pay for medication, and personal motivations and socioeconomic barriers need to be considered when managing a patient’s diabetes (Garber et al., 2017). Keeping these factors in mind, it is important to recognize oral antihyperglycemic agents, such as Metformin as being among the most economically feasible drugs for patients with diabetes, while reducing the risk of hypoglycemia. Metformin has also been associated with higher patient adherence when compared to insulin injections (Capoccia, Odegard, & Letassy, 2015). Patients tend to be less adherent to insulin injections because of the stigma and fear of insulin. This is exacerbated by the fact that insulin is also much more expensive and requires extra supplies and training for proper administration (Capoccia et al., 2015).
MH, a 60-year-old African-American male, was referred to an endocrinology clinic for follow-up from an Advanced Practice Nurse. The patient originally presented to the emergency department 6 months before his visit. His chief complaints included frequent urination, excessive thirst, blurred vision, and a 15-pound weight loss over a period of 3 weeks. At the time of the emergency visit, the patient denied any medical history and did not take any medications. During the emergency room workup, the patient’s BG was revealed to be 723 mg/dl, with an anion gap of 20 (indicating acidosis), and a subsequent A1C reading was 13.8%. No lab values pertaining to the presence of insulin antibodies or beta-cell function were drawn at this time. The patient was admitted to the hospital with a diagnosis of diabetic ketoacidosis, and the endocrinology service was consulted for evaluation and treatment. The patient was started on insulin while in the hospital and also received counseling on changes that he should make regarding his diet and exercise. After a stay of three days, the patient was given teaching regarding medication and follow-up information. MH was discharged on insulin therapy, and he was also given education regarding the possibility of hypoglycemic episodes; how to identify them and what to do when they occur. The patient’s discharge medications were listed as:
Insulin glargine (Lantus) 20 units subcutaneous (SQ) before bedtime
Insulin lispro (Humalog) 8 units SQ with breakfast, lunch, and dinner
Insulin lispro (Humalog) sliding scale for BG correction 1U for BG of 150–199, 2U for BG of 200–249, 3U for BG of 250–299, 4U for BG of 300–349, and 5U for BG of 350–400
For BG greater than 400, patient was instructed to call the endocrine clinic for guidance
Metformin 500 mg by mouth (PO) twice daily
Three months after discharge from the hospital, MH followed up in the endocrinology clinic. At that time, MH denied any symptoms of continued weight loss, excessive thirst, frequent urination, or blurred vision. MH also reported that he had cut “sweets and pop from (his) diet” following a recommendation from a registered dietician who offered education during his hospital stay. MH also stated that he was “trying to exercise more by walking (his) dog in the evening after dinner.” He also reported checking his BG 4 times daily with readings ranging from 71 to 131 mg/dl, denying any symptoms of hypoglycemia. The patient’s urine exhibited no evidence of microalbuminuria. A blood sample was drawn revealing a hemoglobin A1C level of 4.7%. At the time of this visit, MH was instructed to stop taking insulin and remain only on Metformin 500 mg PO twice daily. Antihypertensive agents and aspirin therapy were deferred to his primary care provider for management.
The patient presented to the nurse practitioner for follow-up, having been off of insulin for 4 months and taking only Metformin 500 mg PO twice daily. MH reported that he “felt good,” he had been married for 30 years, and he ran his own landscaping business, which keeps him on his feet moving heavy equipment around most of the day, but he was able to identify that he drank “a lot of pop” when he was thirsty at work. MH denied smoking, alcohol, or drug use. MH stated that he had maintained his dietary and activity changes and he had noticed modest weight loss of 5 pounds in the past 3 months. MH reported that he continued testing his BG several times daily with readings consistently less than 100 mg/dl. MH had also been to see an ophthalmologist per recommendations from the endocrinologist to assess for retinopathy; he reported that they told him his “eyes were fine.” The following data were collected during the follow-up appointment with the nurse practitioner.
Metformin 500 mg PO Daily
Patient’s Mother: type 2 diabetes, hypertension
Patent’s Father: hypertension
Patient’s Brother: type 2 diabetes
Review of systems
General: negative for fever, chills, and sweats
Ears, nose and throat: no nasal bleed or ear discharge, no visual deficits, no issues with dentition
Respiratory: negative for shortness of breath, exercise intolerance, hemoptysis, and wheezing
Cardiovascular: negative for chest pain, paroxysmal nocturnal dyspnea, palpitations, edema, and claudication
Gastrointestinal: negative for vomiting, hematemesis, melena, abdominal pain, bloating, or diarrhea.
Musculoskeletal: negative for joint swelling and muscle weakness
Genitourinary: negative for incontinence, hematuria, and erectile dysfunction
Neurological: negative for headaches, dizziness, numbness, and weakness
Psychiatric: no severe depression or suicidal ideation
Hematological: no lymphadenopathy or excessive bruising
Skin: no rash
Temp 97.9 F Oral; BP 138/68; heart rate 65; respirations 16; SpO2 99%; height 178 cm; weight 95.5 kg; body Mass Index (BMI) 30.1.
General: alert, cooperative, no distress
HEENT: normocephalic, atraumatic, moist and pink mucous membranes, external ears without abnormality
Eyes: Conjunctivae/corneas clear, no icterus, extra ocular movement intact
Neck: supple, symmetrical, trachea midline, no adenopathy, thyroid not enlarged, no tenderness/mass
Chest/lung: Normal respiratory effort, lungs clear to auscultation
Cardiac: regular rate and rhythm, S1, S2, no murmur, no displaced point of maximal impulse
Abdomen: soft, obese abdomen, not rigid, no distension, no tenderness, no rebound, no mass, bowel sounds positive; no costovertebral tenderness
Musculoskeletal: extremities atraumatic, full range of motion all extremities, no lower extremity edema present
Skin: warm and dry, no lesions, discoloration, or breakdown
Neuro: alert and oriented to person, place and time, normal mental status and speech, cranial nerves 2–12 intact, muscle tone and strength normal and symmetric, reflexes normal and symmetric, normal coordination, and monofilament test reveals no evidence of impaired sensation
Relevant lab studies
See "Laboratory results" (Table 2).
Assessment and Plan
Ketosis-prone type 2 diabetes
Continue self-BG checks 4 times daily, before meals and at bedtime. Instructed patient to continue to maintain a log of recordings.
Due to the control exhibited with the biguanide, Metformin, MH was instructed to continue taking Metformin 500 mg PO twice daily.
Instructed MH to follow notify clinic if BG remains elevated above 200 mg/dl for more than 48 hours.
Instructed MH to seek emergent care if he experienced signs and symptoms of ketoacidosis: frequent urination, thirst, shortness of breath, abdominal pain, nausea/vomiting coupled with hyperglycemia. MH was also educated regarding the use of keto urine strips for home use.
Instructed MH to maintain medication regimen during instances of illness or infection and to maintain diligent observation of BG during these periods. Questions or concerns during this time should prompt MH to contact the clinic for guidance.
Reinforced principles of diet and exercise therapy
Encouraged diet high in polyunsaturated and monounsaturated fatty acids with limited intake of saturated fatty acids and trans fats
Limit intake of foods high in carbohydrates
Referred to a registered dietician
Recommended 150 minutes per week of medium intensity exercise divided into five 30-minute sessions.
Follow-up in 3 months. If A1C remains controlled, MH may follow-up with his primary care physician for continuation of care.
Hyperlipidemia (elevated cholesterol and lowdensity lipoprotein (LDL))
Atorvastatin 10 mg PO at bedtime
Assess lipid panel in 3 months to minimize the risk for atherosclerotic cardiovascular disease (ASCVD)
Obesity (BMI 30.1)
Continued reinforcement of diet and exercise therapy
MH’s A1C level demonstrates a maintenance of adequate BG control. An A1C of <6.5% is the goal for many patients with diabetes, given that is achieved in a safe and affordable manner (Garber et al., 2017). For patients taking only Metformin, the goal A1C is <7.5%, which MH qualifies for (Garber et al., 2017). The lab work ordered also reveals no evidence of renal involvement in the progression of his diabetes, as his creatinine, blood urea nitrogen, and urine microalbumin levels were all within normal limits.
Other diagnostic studies that were not completed during the initial hospitalization but may have been warranted would include, which may differentiate type 1 from type 2 DM. For instance, C-peptide levels mimic the amount of insulin being produced by beta cells. In patients with ketosis-prone type 2 DM, C-peptide levels may be low, as insulin production has been suppressed. This test is not very sensitive in patients with ketosisprone type 2 DM as it may falsely identify them as a person having type 1 DM. A glutamic acid decarboxylase autoantibody test identifies antibodies built specifically against the insulin-producing beta cells of the pancreas (Tsai, 2015). In patients with ketosis-prone type 2 DM, these antibodies would not be present as they are lacking the autoimmune component experienced by people with type 1 DM. Other less commonly used diagnostic tests may help differentiate type 1 and type 2 DM and include tests for insulin antibodies, insulinoma antibodies, islet cells cytoplasmic antibodies, and zinc transporter antibodies, which are the newest tests and least readily available (Tsai, 2015).
Although the scope of type 2 DM management falls well within the realm of treatable conditions, it is important for advance practice nurses to be able to differentiate the subtypes of diabetes. With the worldwide prevalence of type 2 DM expected to nearly double in the next 20 years, practitioners may expect to see an increasing number in patients with ketosis-prone type 2 DM as well (Guariguata et al., 2014). As with the patient in this case, it is plausible for patients to resume follow-up with their primary care provider once A1C levels have stabilized provided that exacerbation be closely watched for and the patient is educated appropriately. According to the 2017 guidelines put forth by the American Association of Clinical Endocrinologists (AACE), patients may remain on monotherapy with Metformin as long as their A1C remains less than 7.5% (Garber et al., 2017). In the case of MH, who left the endocrine clinic with an A1C of 5.2% while on Metformin only, his disease could certainly be managed by an adult primary nurse practitioner despite the complexity of initial diagnosis and insulin treatment.
The AACE guidelines also place strong emphasis on lifestyle modification to reduce the risk of diabetic complications as well as ASCVD, which patients with diabetes have an increased susceptibility for (Garber et al., 2017). Patients with ketosis-prone type 2 DM also benefit from nutritional therapy, increased physical activity, adequate levels of sleep, and screening for obstructive sleep apnea if necessary, behavioral support to promote engagement in disease management, and tobacco cessation education if the patient is a tobacco user (Garber et al., 2017). Addressing these issues not only improves glycemic control but also reduces the risk of diabetic complications and ASCVD and is well within the scope of an advanced practice nurse.
Further management of comorbid conditions is also recommended by the AACE, which includes BP and lipid level management. Statin therapy is warranted for patients with elevated LDLs, triglycerides, and total cholesterol (Stone et al., 2014), while patients with hypertension benefit from angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers-type drugs (James et al., 2014). These recommendations mirror those endorsed by the American Academy of Family Physicians and both family and adult primary nurse practitioners.
MH’s diagnosis of ketosis-prone type 2 DM was not as common as traditional type 2 diabetes; however, the principles of management are similar. The focus is on glycemic control either through increasing exogenous insulin as with type 1 diabetes or by increasing sensitivity to insulin more commonly seen with type 2 diabetes. The severe insulin resistance experienced by MH led to an eventual acute failure of the beta cells as they tried to keep up with the insulin demands of the body. This acute failure manifested itself with the signs and symptoms of a more traditional diagnosis of DKA and included hyperglycemia, an elevated anion gap metabolic acidosis, polyuria, polydipsia, and weight loss. Although MH was initially placed on insulin, he employed the tools of diet and exercise and was eventually able to minimize his oral medication intake with simply Metformin. Metformin is listed as a first-line medication by the AACE guidelines (Garber et al., 2017). Metformin (Glucophage) acts to reduce hepatic glucose production while also decreasing insulin resistance. Metformin can be titrated to a dose of 2,000 mg PO twice daily and is a relatively inexpensive drug, covered by MH’s insurance. Metformin is generally well tolerated apart from some transient nausea and other GI side effects such as bloating, flatulence, and diarrhea. To reduce this incidence, patients are encouraged to not take Metformin on an empty stomach (Rojas & Gomes, 2013). MH, however, denied any of these symptoms during a review of systems in his last office visit.
With his decreased insulin resistance and subsequent improved beta-cell effect, MH’s A1C dropped from 13.8% to 5.2%. This greatly reduced his risk of diabetic and atherosclerotic complications and will ideally prolong his functional life. The identification of hyperlipidemia and the addition of a statin to his medication regimen will further reduce his risk of ASCVD. Although initial hospital treatment was highly complex, the current principles of health maintenance that MH utilized can easily be monitored and reinforced by an advanced practice nurse as MH continues to follow-up with a primary care provider.
The fact that MH had been adhering to guidance offered by a registered dietician whom he saw during the hospital visit demonstrated his use of adequate selfmanagement skills. Other factors that will diminish long-term risk factors include his ongoing ability and willingness to check his BG 4 times daily, before meals and at bedtime, as well as his increased exercise regimen. MH exhibited an interest in disease maintenance as he had been to the ophthalmologist after recommendations from the endocrinologist. It is likely that MH, given that he maintains the current level of glycemic control, will have minimal long-term complications related to his diagnosis of ketosis-prone type 2 diabetes.
Implications for practice
Advanced practice nurses utilize a holistic model that has long taken into account patients’ motivations as well as using adjunctive methods of managing disease, such as promoting diet and exercise. advanced practice nurses (APNs) are also trained to place a great deal of emphasis on patient education, which allows a patient with diabetes to maximize their self-management capabilities. Equipped with adequate knowledge of uniquely difficult cases such as those involving ketosis-prone type 2 DM, APNs are well suited to manage these patients and reduce the risk of future complications.
Balasubramanyam, A., Nalini, R., Hampe, C. S., & Maldonado, M. (2008). Syndromes of ketosis-prone diabetes mellitus. Endocrine Reviews, 29, 292–302.
Canfield, C. (2014). Mind the Gap: Navigating the Underground World of DKA. Retrieved from https://my.clevelandclinic.org/ccf/media/Files/nursing/critical-care/2014-mind-the-gap.pdf?la=en.
Capoccia, K., Odegard, P. S. & Letassy, N. (2015). Medication adherence with diabetes medication. The Diabetes Educator, 40, 34–71.
Cefalu, W. T. (2017). Standard of medical care in diabetes. The Journal of Clinical and Applied Research and Education, 40, S1–S135.
Centers for Disease Control. (2014). Number (in thousands) of hospital discharges with diabetic ketoacidosis (DKA) as first-listed diagnosis, United States, 1988–2009. Retrieved from http://www. cdc.gov/diabetes/statistics/dkafirst/fig1.htm.
Garber, A. J., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bloomgarden, Z. T., Bush, M. A., … Umpierrez, G. E. (2017) Consesus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm. Endocrine Practice, 23, 1–32.
Guariguata, L., Whiting, D., Hambleton, I., Beagley, J., Linnenkamp, U., & Shaw, J. (2014). Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Research and Clinical Practice, 103, 137–149.
James, P., Oparil, S., Carter, B., Cushman, W., Dennison-Himmelfarb, C., Handler, J., … Ortiz, E. (2014). 2014 evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eight Joint National Committee (JNC 8). JAMA, 311, 507–520.
Khardori, R. (2017). Type 2 diabetes mellitus clinical presentation: History, physical examination. Retrieved from http://emedicine. medscape.com/article/117853-clinical.
Patel, S. G., Hsu, J. W., Jahoor, F., Coraza, I., Bain, J. R., Stevens, R. D., … Balasubramanyam, A. (2013). Pathogenesis of A2b+ ketosis-prone diabetes. Diabetes, 62, 912–922.
Puttanna, A., & Padinjakara, R. (2014). Diabetic ketoacidosis in type 2 diabetes mellitus. Practical Diabetes, 31, 155–158.
Rojas, L. B. A. & Gomes, M. B. (2013). Metformin: An old but still the best treatment for type 2 diabetes. Diabetes & Metabolic Syndrome, 5, 6.
Spollett, G. (2003). Case study: A patient with uncontrolled type 2 diabetes and complex comorbidities whose diabetes care is managed by an advanced practice nurse. Diabetes Spectrum, 16, 32–36.
Steenkamp, D. W., Alexanian, S. M., & Sternthal, E. (2014). Approach to the patient with atypical diabetes. CMAJ, 186, 678–684.
Stone, N., Lichtenstein, A., Merz, N., Blum, C., Eckel, R., Goldberg, A., … Wilson, P. W. (2014). 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. Journal of the American College of Cardiology, 63, 2889–2934.
Tsai, A. (2015). 6 Tests to Determine Diabetes Type. Retrieved from http://www.diabetesforecast.org/2015/sep-oct/tests-to-determine-diabetes.html.
Whyte, M. B. (2015) Patients with Ketosis-prone type 2 diabetes appear more insulin resistant than patients with non-ketotic type 2 diabetes at the time of acute destabilisation In: Diabetes UK Professional Conference 2015, 2015-03-11 - 2015-03-13. London, UK: ExCeL.