Diabetes Mellitus Case File

Diabetes Mellitus Case File

Eugene C. Toy MD, Donald Briscoe, MD, FA  AFP, Bruce Britton, MD, Joel J. Heidelbaugh, MD, FA  AFP, FACG

Case 51

A 30-year-old obese woman presents to your office with a chief complaint of recurrent yeast infections and increased thirst. She also has noticed increased urinary frequency, but believes this is related to her yeast infection. Over the last several years, she has gained more than 40 lb despite having tried numerous diets, most recently a low-carbohydrate, high-fat diet. The patient's only other pertinent history is that she was told to"watch her diet" during pregnancy because of excessive weight gain. Her baby had to be delivered at 38 weeks via cesarean section because he weighed more than 10 lb (>4500 g). Her family history is unknown, as she was adopted. On physical examination, her blood pressure is 145/92 mm Hg, her pulse is 72 beats/min, and her respiratory rate is 16 breaths/min. Her height is 65 in and her weight is 223 lb (body mass index [BMI] = 37.1). Her physical examination reveals darkened skin that appears to be thickened on the back of her neck and moist, reddened skin beneath her breasts. Her pelvic examination reveals a thick, white, vaginal discharge. A wet preparation from the vaginal discharge reveals branching hyphae consistent with Candida species. A urinalysis is negative for leukocyte esterase, nitrites, protein, and glucose.

⯈ What is the most likely primary diagnosis for this patient?

⯈ What physical findings are suggestive of the diagnosis and have implications for management?

⯈ What diagnostic studies should be ordered at this time?

ANSWER TO CASE 51

Diabetes Mellitus

Summary: A 30-year-old obese woman presents with a recurrent yeast infection, polydipsia, and polyuria. She has gained over 40 lb despite efforts to lose weight, and was told to "watch her diet" during a recent pregnancy. On examination, she has a BMI of 37.l, acanthosis nigricans, Candida vaginitis, and a negative urinalysis.

• Most likely diagnosis: Type 2 diabetes mellitus.
• Significant physical findings: Obesity, acanthosis nigricans, blood pressure that is elevated for a diabetic (JNC 8 blood pressure goal in the diabetic patient is <140/90 mm Hg), Candida vaginitis, and likely Candida skin infection under her breasts.
• Diagnostic studies: Fasting serum glucose measurement or glycosylated hemoglobin level (HbA1c); follow-up testing should include a comprehensive metabolic panel including electrolytes, blood urea nitrogen (BUN), and creatinine; fasting lipid panel; urine microalbumin/ creatinine ratio.

ANALYSIS

Objectives

1. Know the diagnostic criteria for diabetes mellitus, including classic signs and symptoms, physical findings, and diagnostic studies.
2. Know the pathophysiologic and epidemiologic differences between types 1 and 2 diabetes mellitus.
3. Learn the treatment options for diabetic patients.
4. Be aware of the acute emergencies that can occur in diabetic patients and how to manage them.

Considerations

Diabetes mellitus is one of the most common medical problems encountered in medical practice, and was the seventh leading cause of death in the United States in 2011. In 2012, there were an estimated 29.1 million diabetics in the United States and the number is increasing both in the United States and worldwide. It was estimated that of the 29.1 million people, 21 million were diagnosed, and 8.1 million were undiagnosed. Diabetes affects all ethnic groups, but there is a disproportionate burden of disease in African Americans, Native Americans, and Hispanics. The global epidemic of obesity has led to a dramatic increase in the number of type 2 diabetics presenting with disease in their teens and twenties. While some diabetics exhibit the classic symptoms of polyuria, polydipsia, polyphagia, and weight loss, many patients are diagnosed when asymptomatic.

The complications of diabetes are myriad. Diabetics are 6 to 10 times more likely than nondiabetics to be hospitalized for cardiovascular disease and 15 times more likely to be hospitalized for peripheral vascular disease. It is the leading cause of blindness in working-age adults in the United States, most of which is preventable. It is also the leading cause of end-stage renal disease requiring dialysis and of nontraumatic amputations. The American Diabetes Association (ADA) estimates the annual cost of diabetes in the United States, including direct medical costs and lost productivity, at $245 billion per year.

Other common complications of diabetes include neuropathic, gastrointestinal, and immunologic disease. Peripheral neuropathy, leading to reduced sensation or pain, can lead to the development of injuries, ulcerations, infections, or amputations of the extremities. Gastroparesis can be a chronic problem that causes nausea and vomiting and impairs the patient's ability to maintain an adequate nutritional status. Poorly controlled diabetics suffer relative immunosuppression that makes them more prone to opportunistic infections, including bacterial and fungal skin and genitourinary infections.

Impaired glucose tolerance or elevated serum glucose levels may be present for years prior to a formal diagnosis of type 2 diabetes mellitus. In the case presented, the history of excessive weight gain during pregnancy with fetal macrosomia and advice to "watch her diet" should prompt the clinician to suspect a history of gestational diabetes. Women who have gestational diabetes are at a threefold increased risk of developing diabetes later in life.

The symptoms of polydipsia and polyuria should lead the clinician to an increased suspicion for the possibility of diabetes. High serum glucose levels function as an osmotic diuretic, resulting in frequent urination. Patients with diabetes also may present with polyphagia, as their insulin deficiency prevents food intake from being properly metabolized, resulting in a state of hunger for which they will frequently eat but not feel satiated.

DIAGNOSIS

The American College of Endocrinology diagnostic criteria for diabetes are any of the following:

1. A fasting plasma glucose greater than or equal to 126 mg/ dL (no caloric intake for at least 8 hours)
2. A plasma glucose greater than or equal to 200 mg/ dL 2 hours after a 75-g glucose load (ie, glucose tolerance test)
3. Random plasma glucose greater than or equal to 200 mg/ dL plus symptoms ( eg, polydipsia, polyuria)
4. Glycosylated hemoglobin (HbA1c) greater than or equal to 6.5%

HbA1c, is used to estimate the average glucose levels over the past 3 months in those who are diagnosed with diabetes for appropriate monitoring and goal setting. A HbA1c, less than 6% is considered as a normal value, while values between 6% and 6.5% are considered "pre-diabetes." In patients with hemoglobinopathies ( eg, sickle cell anemia), recent blood loss, or a recent drastic change in diet (eg, no or extremely low-carbohydrate diet), serum fructosamine levels should be obtained, and indicate average glucose levels over a 2- to 3-week period.

Measurement of C-peptide and insulin levels can be used to distinguish type 2 from type 1 diabetes when the history, physical examination, and other tests, such as serum ketones and osmolality, are not enough. Other tests recommended by the ADA are fasting lipid profiles (at the time of diagnosis and, at least, annually thereafter), serum creatinine, urinalysis, urine microalbumin: creatinine ratios (at time of diagnosis in type 2 diabetics and annually thereafter; in type 1 diabetics who have had disease for 5 years and annually thereafter), annual dilated eye examinations, regular foot examinations, electrocardiography (ECG) (in adults), and, in type 1 diabetics, thyroid disease screening with a thyroid-stimulating hormone (TSH).

The absence of glucose on urinalysis does not exclude a diagnosis of diabetes and should not delay a blood glucose measurement. Glucosuria occurs when the blood glucose level is greater than the renal "threshold" level, often estimated at a serum level of 180 mg/ dL, the level that approximates a glycosylated hemoglobin level of 8.0%. Overt signs of insulin resistance ( eg, acanthosis nigricans, elevated blood pressure, obesity) also make the diagnosis of type 2 diabetes more likely.

The general approach to managing diabetes mellitus is aimed at secondary prevention of macrovascular ( eg, accelerated coronary artery disease, accelerated cerebral and peripheral vascular disease) and microvascular (eg, retinopathy, nephropathy, and neuropathy) complications.

Approach To:

Diabetes Mellitus

DEFINITIONS

AACE/ACE: American Association of Clinical Endocrinologists and American College of Endocrinology-Organization who devised the current clinical practice guidelines for a comprehensive care plan for diabetes mellitus.

TYPE 1 DIABETES: Often referred to as juvenile diabetes, the exact pathophysiologic mechanism is unknown, yet thought to be likely an autoimmune disorder. Current theories support the notion that either an infection or an environment or genetic trigger causes the body to mistakenly attack pancreatic β-cells that make insulin.

CLINICAL APPROACH

Diabetes mellitus is a general term for several different variations of disease along a spectrum that result in high blood glucose levels that, if uncontrolled over a period of time, eventually lead to microvascular and macrovascular complications. The major classifications of diabetes mellitus are types 1 and 2 diabetes and gestational diabetes.

Type 1 Diabetes

Type 1 diabetes (insulin-dependent diabetes mellitus (IDDM]) is a chronic disease of carbohydrate, fat, and protein metabolism due to a lack of insulin, resulting from autoimmune destruction of insulin-producing pancreatic β cells. Due to the lack of insulin, which is required for glucose and carbohydrate metabolism, type 1 diabetics are prone to metabolize fats, with the resultant production of ketones. This process leads to diabetic ketoacidosis (DKA), a syndrome characterized by hyperglycemia, high levels of serum acetone, and β-hyroxybutyrate, and an anion gap metabolic acidosis. DKA often occurs during times of physical stress, such as an infection or myocardial infarction, or when the patient does not properly take his or her insulin. DKA is a medical emergency requiring hospitalization, vigorous intravenous hydration with normal saline, correction of the acidosis and electrolyte disturbances, aggressive insulin management, and evaluation for the underlying cause of the condition.

Type 2 Diabetes

Type 2 diabetes (previously called adult-onset diabetes mellitus (AODM], but still commonly called non-insulin-dependent diabetes mellitus [NIDDM]) patients, in contrast to type 1 diabetics in whom there is a lack of insulin, exhibit insulin resistance in peripheral tissues often related to visceral adiposity and obesity, and may have hyperinsulinemia. Type 2 diabetics often manifest signs of insulin resistance for many years prior to the diagnosis of overt diabetes. This type of diabetes accounts for at least 90% of the diagnosed cases, and virtually all cases of undiagnosed diabetes in the United States.

Type 2 diabetes has a stronger familial predisposition than type 1 diabetes, as type 2 diabetics often have a family history of the disease. The genetic factors are multifactorial and have not been accurately identified. It is strongly associated with obesity and its complications including cardiometabolic syndrome, hyperinsulinemia, hypertension, dyslipidemia, hyperglycemia, and central obesity.

Uncontrolled type 2 diabetics can achieve extremely high blood sugars without developing ketosis and acidosis. This type of diabetes is more prone to hyperosmolar states due to the high blood sugar levels. Hyperosmolar hyperglycemic nonketotic syndrome (HHNS) occurs when blood glucose levels become substantially elevated, often approaching 1000 mg/ dL . This may be the presenting symptom of some cases of type 2 diabetes, or may result from either a concurrent illness or failure to take medications. Serum osmolarity is elevated ( > 320 mOsm/kg) and the patient has a large fluid deficit (up to 9 L). In severe cases, coma or death can occur due to electrolyte abnormalities, dehydration, and the toxic effects of metabolic acidosis. HHNS must be managed with hospitalization, aggressive rehydration with normal saline and correction of electrolyte abnormalities, treatment of underlying illnesses, and the judicious use of insulin.

Gestational Diabetes

Gestational diabetes mellitus (GDM) occurs in approximately 7% of all pregnancies, resulting in over 200,000 cases annually in the United States, with a prevalence of 1 % to 14%. During pregnancy, elevated levels of human placental lactogen, estrogen, and progesterone produced by the placenta act as insulin antagonists leading to increased insulin resistance and carbohydrate intolerance. Maternal and fetal complications related to GDM are numerous. Maternal complications include hyperglycemia, diabetic ketoacidosis (DKA), increased urinary tract infection (UTI) risk, increased pregnancy-induced hypertension/preeclampsia, and retinopathy.

Fetal effects include congenital malformations, macrosomia, respiratory distress syndrome, hypoglycemia, hyperbilirubinemia, hypocalcemia, polycythemia, and hydramnios. Women with GDM are more prone to develop non-pregnancy-related type 2 diabetes and should be screened with a glucose tolerance test postpartum and should undergo annual diabetic screening.

Risk factors for GDM include age greater than 25 years, member of a highincidence ethnic group ( eg, Native American, African American, Hispanic American, South or East Asian, Pacific Islander), BMI of 25 or greater, history of glucose intolerance, previous history of GDM, and history of diabetes mellitus in a first-degree family member.

The American College of Obstetricians and Gynecologists recommends screening all women for gestational diabetes between 24 and 28 weeks' gestation with an oral 50-g 1-hour glucose tolerance test (GTT). If the 1-hour glucose challenge is greater than 135 to 140 mg/dL, then an oral 100-g 3-hour GTT should be performed. The 3-hour GTT requires serum glucose levels be obtained at fasting, 1-, 2-, and 3-hour intervals. The diagnosis of GDM is made based on two or more abnormal results, defined as glucose levels of 95, 180, 155, and 140 mg/dL, respectively. GDM is treated with strict dietary management via patient education and nutritional counseling and when necessary, oral diabetic agents with or without insulin. Increased surveillance for fetal demise in pregnant women with GDM is mandatory, particularly when fasting glucose levels exceed 105 mg/ dL or when pregnancy becomes postterm.

MANAGEMENT

The overall goals for the diabetic patient are to achieve a "controlled" status:

1. Strict glycemic control with a goal of hemoglobin Alc of less than or equal to 7.0%
2. Low-density lipoprotein cholesterol (LDL-C) level less than or equal to l00mg/dL
3. Blood pressure less than or equal to 140/90 mm Hg (JNC 8 guidelines)
4. Lifestyle modifications including a diet consisting of low carbohydrates and low saturated fats and physical activity counseling (at least 150 min/wk of moderate-intensity aerobic physical activity [ 50%-70% maximum heart rate] and resistance training [3 times/wk])

The treatment for type 1 diabetes centers on insulin administration. In most cases, combination therapy using short-acting insulin prior to meals and long-acting basal insulin confers the greatest outcomes in minimizing complications. Insulin pump therapy, which provides a continuous subcutaneous infusion of short-acting insulin, is also an alternative for patients with labile glucose control. Insulin management requires careful and frequent self-monitoring of glucose, often with adjustment of insulin dosage based on the glucose levels, amount of physical activity, and caloric/carbohydrate intake (Table 51-1).

Patients with type 2 diabetes mellitus and those at risk of developing diabetes should be educated on the importance of appropriate calorie-restricted and

Data from the National Institutes of Health. Available at: http://diabetes.niddk.nih.gov/dm/pubs/medicines_ez/insert_

C.htm. Accessed May, 2009.

low-carbohydrate diet and exercise as key components of their management. In some cases, this strategy may be all that is required to achieve appropriate glycemic control. An initial goal that is achievable by many patients is a 10% weight loss. When lifestyle changes alone do not result in adequate glycemic control, oral agents should be considered as first-line treatment in patients with a glycosylated hemoglobin level less than 9.0%. For severely obese patients, gastric bypass surgery may be considered when standard treatments fail to improve glycemic control.

Medications for the prevention of diabetes mellitus are currently not recommended but can be considered when lifestyle modifications prove unsuccessful. Several mediations are available for treating type 2 diabetes (Table 51-2). Metformin is the drug of choice to begin with unless contraindications are present.

Biguanides (eg, metformin) act on the liver to decrease glucose output during gluconeogenesis. Secondary actions include improved insulin sensitivity in the liver and muscle and a hypothesized decrease in intestinal absorption of glucose. Metformin can lower the HbAlc by 1.5% to 2%. The UKPDS showed a significant reduction in cardiovascular events, diabetes-related deaths, and all causes of mortality in patients taking metformin. Other advantages to metformin include no potential risk of hypoglycemia, reduced serum insulin levels, potential modest weight loss, and a reduction in triglycerides and LDL cholesterol. The efficacy, safety, and improved outcomes make it a popular first-line agent in type 2 diabetes.

The most common side effects of metformin are gastrointestinal, including nausea and diarrhea. These side effects may be reduced by starting at low doses and taking the medication with meals. The most dangerous side effect attributable to metformin is the development of lactic acidosis. This risk is potentially fatal and is increased by renal insufficiency and chronic kidney disease, thus metformin use is contraindicated in those with a serum creatinine greater than or equal to 1.5 mg/dL in men and greater than or equal to 1.4 mg/dL in women, hepatic insufficiency, or congestive heart failure. Metformin should be withheld 48 hours prior to any imaging that requires iodinated contrast. Metformin is classified as category B in pregnancy and thought to be safe in nursing mothers. It is the oral agent of choice in type 2 diabetes in children older than age 10.

Sulfonylureas were the first oral agents available for the treatment of type 2 diabetes. Their principal action is to function as insulin secretagogues that stimulate

Abbreviations: CHF, chronic heart failure; DPP. dipeptidyl peptidase; GI, gastrointestinal; GLP. glucagon-like peptide;

Ml, myocardial infarction;TID, three times daily;TZD, thiazolidinedione.

Data from Nathan DM, Buse JB, Davidon MD, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus

algorithm of initiation and adjustment of therapy. Diabetic Care. 2008;31(12):1-11.

pancreatic β-cells to secrete insulin. Advantages include a potential 2% reduction in HbA1c, once- or twice-a-day dosing, and relatively low cost. Disadvantages include poor response in 20% of patients, a tendency of users to gain weight, and a tendency for the medications to lose effectiveness over time. As insulin secretagogues, sulfonylureas carry a risk of causing hypoglycemia.

Sulfonylureas and insulin are considered to be the best validated second-line add-on therapy. The following medications are less well validated. Further studies are necessary to determine how these agents may play a role in the overall longterm management of type 2 diabetics.

The principal action of thiazolidinediones (TZDs), or glitazones (eg, rosiglitazone), is to improve insulin sensitivity in muscle and adipose tissue. Secondary actions include decreased hepatic gluconeogenesis and increased peripheral glucose utilization. Among their advantages is a modest decrease in serum triglyceride and increase in high-density lipoprotein (HDL) cholesterol levels. Since they are metabolized in the liver, they can be used in patients with renal impairment. They also do not, when used by themselves, cause hypoglycemia. Disadvantages include edema and weight gain, which is of significant concern in patients with congestive heart failure, liver disease and cirrhosis, chronic kidney disease, and chronic lower extremity edema. Since their release, several members of this class of medication have been withdrawn from the market due to increased risk of cardiovascular events. Thus, there is controversy over whether or not the benefits of this class of medications outweigh potential risks.

Meglitinides ( eg, nateglinide) are short-acting secretagogues that increase insulin secretion from the pancreas and work in a similar fashion to sulfonylureas. These medications are taken no more than 1 hour prior to meals due to the rapid onset and short duration of action. They are useful in patients whose blood glucose values vary at mealtime but who have controlled fasting glucose levels. They reduce HbA1c, levels from 0.5% to 2%. The disadvantages include a risk of hypoglycemia, especially if the medication is taken but no meal is then eaten, and expense. They should not be used in patients with hepatic dysfunction.

α-Glucosidase inhibitors (eg, acarbose) delay carbohydrate absorption by inhibiting a-glucosidase in the small intestine, which decreases postprandial hyperglycemia. They reduce HbA1c, levels by 0.7% to 1.0%. This class of medication may offer benefits to patients with erratic eating habits, as hypoglycemia will not occur if meals are skipped. The principal side effects are gastrointestinal, including flatulence. These medications are contraindicated in cases of ketoacidosis and in patients with hepatic dysfunction.

Pramlintide is an amylinomimetic agent that has physiologic actions equivalent to those of human amylin, a glucoregulatory hormone synthesized by pancreatic β-cells and released with insulin in response to a meal. It inhibits inappropriately high glucagon secretion during episodes of hyperglycemia (eg, after a meal) in patients with type 1 or 2 diabetes mellitus and does not impair normal glucagon response to hypoglycemia. It is administered subcutaneously and does not require dose adjustments for renal or hepatic impairment, but requires titration to balance hypoglycemia and preprandial glycemic control. It reduces HbA1c, levels by 0.5% to 1.0%. Known side effects include hypoglycemia, nausea, and diarrhea, often dosing.

GLP-1 agonists, or glucagon-like peptide-1 incretin mimetics ( eg, exenatide), are synthetic peptides that stimulate insulin release. This class can be used as adjunctive therapy for type 2 diabetics with inadequate glycemic control while also taking either metformin, a sulfonylurea, and/ or a thiazolidinedione/glitazone. They reduce HbA1c levels by 0.5% to 1.0%. A distinct benefit of this class is early satiety, which can improve dietary management. This class should be avoided in patients with diabetic gastroparesis. Side effects include hypoglycemia when added to a sulfonylurea (but not when added to metformin), nausea, vomiting, diarrhea, and acute pancreatitis.

DPP-4 inhibitors, or dipeptidyl peptidase-4 inhibitors (eg, sitagliptin), work via an enzyme that inactivates incretin hormones GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). GIP and GLP-1 stimulate insulin synthesis and release from pancreatic β-cells in a glucose-dependent manner. GLP-1 also decreases glucagon secretion from pancreatic a-cells in a glucose-dependent manner, leading to reduced hepatic glucose production. This class can be used as monotherapy and as an adjunct to diet and exercise for management of type 2 diabetes mellitus in patients whom hyperglycemia cannot be controlled by diet and exercise alone. They can also be used in combination with metformin, a sulfonylurea, or a thiazolidinedione as second-line therapy for management of type 2 diabetes mellitus in patients who do not achieve adequate glycemic control with diet, exercise, and metformin, sulfonylurea, or thiazolidinedione monotherapy. The DPP-4 inhibitors have been shown to reduce HbA1c levels by 0.5% to 0.8%. The principal side effects include upper respiratory tract symptoms and severe hypersensitivity ( eg, requires titration to balance hypoglycemia and preprandial glycemic control anaphylaxis and/or angioedema).

The goal of diabetic management is to safely and consistently lower the average serum glucose levels to reduce the risk of macrovascular and microvascular complications. The goal of treatment is to achieve a HbA1c of less than 7%, although some authorities advocate 6.5% as a goal. Other treatments are equally important to achieve tight glucose control in the effort to reduce adverse events, including heart attacks and strokes. The JNC 8 concluded that a blood pressure goal of less than 140/90 mm Hg reduces cardiovascular events. Diabetes is considered a coronary heart disease risk equivalent for decisions regarding lipid management. The LDL cholesterol goal is less than 100 mg/dL. All diabetics should be advised to be immunized with the pneumococcal vaccine and to get an annual influenza vaccination. They should be screened annually for diabetic neuropathy with a monofilament examination of the feet, should have annual microalbumin screening for diabetic nephropathy, and an annual dilated ophthalmologic evaluation to screen for diabetic retinopathy.

MANAGEMENT OF HYPOGLYCEMIA

Hypoglycemic symptoms are related to the central and sympathetic nervous systems. Decreased levels of glucose lead to deficient cerebral glucose availability that can manifest as confusion, difficulty with concentration, irritability, hallucinations, focal impairments (eg, hemiplegia), and eventually coma and death. Stimulation of the sympathoadrenal nervous system leads to sweating, palpitations, tremulousness, anxiety, and hunger. Causes of hypoglycemia include fasting, exogenous insulin, elevated C-peptide levels, autoimmunity, sulfonylurea abuse, and hormonal deficiency (eg, hypoadrenalism, hypopituitary, glucagon deficiency).

When hypoglycemia is suspected and the patient is conscious and cooperative, juice, soda, candy, or some other sugar-containing product can rapidly alleviate the symptoms on a temporary basis. If the person is not able to take something by mouth, rapid administration of intramuscular glucagon can be effective. In the hospital setting, or when intravenous access is available, a rapid injection of 50% dextrose (D50) quickly restores normal serum and brain glucose levels. Following any of these therapies, the patient should be closely monitored, as the hypoglycemia may recur (especially if the patient uses a long-acting insulin or oral hypoglycemic agent), unless additional glucose and/or carbohydrates are administered.

COMPREHENSION QUESTIONS

51.1 A 16-year-old adolescent girl has had an increased craving for sweets. She often consumes two to three ice cream sundaes and four large sodas a day, but has still managed to maintain her weight. Friends often notice her using the bathroom more frequently to urinate but she denies any episodes of purging and states that she just has to urinate after drinking so much cola. On physical examination, she is 5 ft 8 in and 110 lb and her thyroid is not palpable.

Which of the following test results is diagnostic of diabetes mellitus?

A. A single glucose reading of 124 mg/dL

B. A 2-hour oral glucose tolerance test greater than 200 mg/dL with a 100-g glucose load

C. A random glucose greater than 200 mg/dL with symptoms such as polydipsia or polyuria

D. A HbAlc of 6.3%

51.2 A 7 -year-old boy is brought to the office with symptoms of polydipsia, polyphagia, polyuria, and weight loss of 8 lb. For the past 24 hours, he has had abdominal pain and vomiting. A urinalysis performed in the office shows the presence of glucose and ketones. A finger-stick blood glucose is 530 mg/ dL.

Which of the following is the most appropriate initial management in this patient?

A. Discharge home with oral metformin and a prompt referral to a dietician.

B. Hospitalization with administration of intravenous normal saline and 5% dextrose, and regular insulin.

C. Discharge home with a prescription for insulin, advice to hydrate aggressively, and office follow-up in 24 hours.

D. Hospitalization with determination of electrolytes and potential anion gap acidosis, and administration of intravenous normal saline and regular insulin.

E. Hospitalization with immediate endocrinology consults for insulin dosing.

51.3 An 83-year-old man was diagnosed with type 2 diabetes mellitus 3 months ago. He has modified his diet and tries to walk at least half a mile every evening. He drinks a glass of wine with lunch and dinner daily. For the past week, he has felt dizzy upon standing and has fallen on two occasions, but has never lost consciousness. After the last episode of falling, he presented to the local emergency room (ER) where his blood pressure was 155/76 mm Hg, heart rate was 74 beats/min, and respiratory rate was 16 breaths/min. A finger stick showed a random glucose level of 64 mg/dL. Which of the following classes of medications has the lowest incidence of causing hypoglycemia when used as single-agent therapy?

A. Biguanide

B. Insulin

C. Sulfonylurea

D. Meglitinide

51.4 A 39-year-old GlPO woman who is a new patient presents to the office at 10 weeks' gestation. She is known to have type 2 diabetes mellitus and currently takes metformin. Her last HbA1c, was 10.4% 1 month ago. Her urinalysis is negative for ketones and leukocytes, and reveals only trace protein. She has no other medical problems and does not drink or smoke. On physical examination, she is 5 ft 4 in and weighs 202 lb with a BMI of 34.7. She inquires about the risk of diabetes to her fetus. Compared to gestational diabetes mellitus, this patient is at an increased risk for developing which of the following?

A. Fetal malformations

B. Fetal macrosomia

C. Polyhydramnios

D. Shoulder dystocia

E. Diabetic gastroparesis

51.5 A 56-year-old man with cardiometabolic syndrome presents to discuss his diabetic management regimen. His last HbA1c was 8.8% and he currently takes metformin twice daily. He adamantly does not want to take insulin. He has seen a lot of commercials for new diabetic agents and wants to try one that will help to curb his appetite. Which of the following agents will likely cause early satiety?

A. Acarbose

B. Rosiglitazone

C. Nateglinide

D. Pramlintide

E. Exenatide

ANSWERS

51.1 C. Diabetes mellitus can be defined by measurement of an 8-hour fasting glucose more than 125 mg/dL; a random glucose of 200 mg/dL or more with classic symptoms or a 2-hour GTT of 200 mg/dL or more after a 75-g glucose load. Recently, the ADA recommended that an HbAlc of greater than or equal to 6.5% can be used for diagnosing diabetes.

51.2 D. This is a classic presentation of diabetic ketoacidosis, a common initial presentation of type 1 diabetes mellitus, and is a medical emergency. This child requires immediate hospitalization, determination of electrolytes and potential anion gap metabolic acidosis, intravenous normal saline, and insulin. Intravenous dextrose should not be administered until the fluid deficit is corrected with normal saline, and the anion gap has been reversed. Metformin will not clinically improve this patient. An endocrinologist is not required for dosing of insulin.

51.3 A. Biguanides (metformin) are effective medications for the treatment of type 2 diabetes; they do not cause hypoglycemia when given as monotherapy. Insulin and insulin secretagogues carry a risk of hypoglycemia as a complication of therapy.

51.4 A. Gestational diabetes is more likely to lead to fetal macrosomia and polyhydramnios. Both gestational and pregestational diabetes are associated with shoulder dystocia. Pregestational diabetes is associated with greater fetal malformations due to the higher serum glucose levels during organogenesis (5- to 10-week gestational age), whereas gestational diabetes tends to be associated with hyperglycemia after 20-week gestation, when the fetal organs have already formed. Preterm labor occurs at same frequency in diabetics as nondiabetics.

51.5 E. Exenatide has been shown to cause early satiety and should be avoided in patients with diabetic gastroparesis. The other medications may cause nausea, diarrhea, or other gastrointestinal side effects, but do not cause early satiety.

CLINICAL PEARLS

⯈ Diabetes is one of the most common diseases encountered in clinical practice, and is often diagnosed in asymptomatic patients. The criteria for diagnosis have been lowered to decrease macrovascular and microvascular complications, including death.

⯈ Type 2 diabetes accounts for more than 90% of all cases of diabetes in the United States. The increasing prevalence of obesity greatly contributes to more patients who will develop diabetes over the course of their lives.

⯈ Biguanides are the mainstay of oral diabetic agents in patients with type 2 diabetes due to tolerability, low cost, efficacy, and demonstrated reduction in morbidity and mortality.

⯈ Newer oral diabetic agents can play an important role in adjunctive therapy when modest reductions in HbAlc are the goal.

⯈ Long-acting insulin should be considered in patients with type 2 diabetes who have insulin resistance and cardiometabolic syndrome.

REFERENCES

American College of Obstetricians and Gynecologists. ACOG guidelines at a glance: gestational diabetes mellitus. Obstet Gynecol. 2013;122:406-416. 

American Diabetes Association (ADA). Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(suppl l):S81-S90. 

American Diabetes Association (ADA). Executive summary: standards of medical care in diabetes-2014. Diabetes Care. 2014;37(suppl l):S5-S13. 

Evert AB, Boucher JL, Cypress M, et al. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care. 2014;37(suppl l):Sl20-S143. 

Handelsman Y, Bloomgarden ZT, Grunberger G, et al. American Association of Clinical Endocrinologists and American College of Endocrinology-Clinical Practice Guidelines for Developing a Diabetes Mellitus Comprehensive Care Plan-2015. Endocr Pract. 2015;21(suppl 1):1-87. 

James PA, Oparil S, Carter BL, et al. Evidence-based guideline for the management of high blood pressure in adults. Report from the panel members appointed to the Eighth Joint National Committee (JNC 8).JAMA. 2014;311(5):507-520. 

Patel P, Macerollo A. Diabetes mellitus: diagnosis and screening. Am Fam Physician. 2010;81(7): 863-870. 

Petznik A. Insulin management of type 2 diabetes mellirus. Am Fam Physician. 2011;84(2):183-190. 

Powers AC. Diabetes mellitus: diagnosis, classification, and pathophysiology. In: Kasper D, Fauci A, Hauser S, et al., eds. Harrison's Principles of Internal Medicine. 19th ed. New York, NY : McGrawHill Education; 2015. Available at: http://accessmedicine.mhmedical.com. Accessed May 25, 2015. 

Powers AC. Diabetes mellitus: management and therapies. In: Kasper D, Fauci A, Hauser S, et al., eds. Harrison's Principles of Internal Medicine. 19th ed. New York, NY : McGraw-Hill Education; 2015. Available at: http://accessmedicine.mhmedical.com. Accessed May 25, 2015. 

Zoungas S, Chalmers J, Neal B, et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl] Med. 2014;371:1392-1406.

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