You are seeing a new patient in your office. He is a 47-year-old man with a presenting complaint of fatigue for several months. He denies fever, rigors, cough, nausea, or diarrhea. He has lost about 10 lb. Upon questioning him you discover that he is also having nocturia most nights and is thirsty all the time. He has asthma, for which he uses an albuterol metered dose inhaler occasionally; he has no other chronic medical problems and takes no other medications on a regular basis. He has a family history of diabetes, hypertension, and heart disease. He smokes about one pack per day, and he works as a teacher at the local high school. He is aware of no occupational exposure to toxins.
Physical examination reveals the following: T 37°C, BP 135/83 mm Hg, P 72 bpm, BMI 38 kg/m2. Aside from obesity, the remainder of the examination is normal.
Laboratory test results reveal the following: normal CBC, BUN/creatinine, and electrolytes. You ask him to return to the office the next day for fasting laboratory tests, which reveal a fasting glucose of 123 mg/dL and an HbA1c of 7.5%.
Question 10.10.1 Does this patient have diabetes?
A) Yes; he has an elevated fasting glucose.
B) Probably; he needs a second fasting glucose to confirm the diagnosis.
C) Probably; he needs a second HbA1c to confirm the diagnosis.
D) Yes; he has the classic symptoms of diabetes: fatigue, weight loss, and thirst, associated with an elevated glucose.
E) Probably not; his HbA1c is not >8%.
Answer 10.10.1 The correct answer is "C." If results of two different diagnostic tests for DM are discordant, the test that is diagnostic of diabetes should be repeated. "A" and "B" are incorrect because the fasting glucose is <126 mg/dL (the threshold for diabetes). "D" is incorrect because we do not have his random glucose value that is ≥200 mg/dL. "E" is incorrect because the A1c cutoff for diabetes diagnosis is ≥6.5%.
There are new guidelines about whom to screen for diabetes (USPSTF, 2015). Screen asymptomatic adults age 40 to 70 years of age who are overweight or obese. Repeat this screening every 3 years. The 2008 USPSTF guideline recommended screening hypertensive adults for diabetes, which has gone the way of the dinosaur for the 2015 guidelines. The 2015 ADA guideline recommends screening all asymptomatic adults every 3 years starting at age 45; earlier screening is recommended for adults at high risk of type 2 diabetes (BMI ≥25 kg/m2; habitual physical inactivity; belonging to a high-risk ethnic or racial group; previously identified impaired glucose tolerance; hypertension; dyslipidemia; history of gestational diabetes or delivery of a baby weighing >9 lb; and polycystic ovary syndrome).
Question 10.10.2 Assuming another A1c is above 6.5%, what further study must be done to complete the diagnosis of diabetes and determine whether the patient has type 1 or type 2 diabetes?
B) Anti-islet cell antibodies.
C) Anti-insulin antibodies
Answer 10.10.2 The correct answer is "D." This patient's age, history, examination (BMI 38), and laboratory findings are consistent with the diagnosis of DM2. None of the other studies listed needs to be performed. However, if questions remain regarding the type of diabetes (which will then affect therapy, prognosis, follow-up, etc.), you may choose to perform further studies. In DM1, the C-peptide level (a marker of endogenous insulin production) is low. If it is equivocal, give a glucose load (e.g., large meal) and see if it goes up. If it goes up, the diagnosis is likely DM2. Anti-islet cell antibodies are present in 80% of type 1 diabetics and, if found, are essentially diagnostic of type 1 diabetes. "D" is incorrect because anti-insulin antibodies have a low sensitivity for DM 1 and may be elevated secondary to the use of exogenous insulin.
To be complete, anti-glutamic acid decarboxylase (anti-GAD) antibodies are present in 70% of patients with DM1 at the time of diagnosis.
Question 10.10.3 The pathologic factors involved in type 2 diabetes in adults include:
A) Pancreatic beta-cell destruction through a yet undetermined infectious process.
B) The production of anti-insulin antibodies that cause precipitation of insulin/antibody complexes.
C) Resistance to the effects of insulin at peripheral tissues and a relative insulin deficiency that is progressive over time.
D) An autosomal-dominant process, with the diabetes gene located on the long arm of chromosome 18.
E) Too much exercise and a complete lack of a "beer gut."
Answer 10.10.3 The correct answer is "C." DM2 is the result of the development of insulin resistance at the peripheral tissues (e.g., fat and muscle cells) and a relative lack of insulin compared to the increasing amount that the body requires. "A" is incorrect. However, autoimmune destruction of beta-cells in the pancreas is responsible for causing DM1. "B" is wrong although there are anti-insulin antibodies found in DM1. "D" is incorrect as well, but there is a strong genetic component to DM2. The exact genetic factors that cause DM2 in adults have not been completely elucidated, but there is no single gene responsible transmitted in an autosomal dominant fashion. "E" is incorrect because lack of exercise, weight gain, dietary factors, and truncal obesity (the "beer gut") predispose persons to the development of DM2.
You meet with the patient and his husband to go over the test results and explain the diagnosis of diabetes. Given his age, body habitus, and lack of exercise, you feel certain that this patient has type 2 diabetes. You provide some basic education on the nature of diabetes, its natural history, and what can be done to manage it.
Question 10.10.4 What is the most important next step for this patient?
A) Initiation of insulin therapy.
B) Initiation of an ACE inhibitor
C) Referral to an endocrinologist.
D) Diabetic education classes.
E) Initiation of glyburide or other sulfonylurea.
Answer 10.10.4 The correct answer is "D." A general education program that includes information on diet, disease management, and the family's role in successful diabetes care is the most important intervention listed. While specialist consultation may be useful in complex diabetic patients or in those who are not responding to treatment, generalist physicians provide care to the majority of patients with diabetes. Insulin therapy is not indicated at this point, and an ACE inhibitor may or may not be helpful depending on the patient's blood pressure and urine protein. "E" is also incorrect (keep reading to learn why).
Upon his return, you find that the patient's blood pressure is elevated. On three separate occasions, he has systolic pressure ≥140 and diastolic pressure ≥90 mm Hg.
Question 10.10.5 Which class of medications is the best choice for initial therapy of hypertension in diabetics?
B) Calcium-channel blockers.
Answer 10.10.5 The correct answer is "A." ACE inhibitors have been shown to provide renal protection in patients with diabetes (types 1 and 2). Patients with albuminuria and hypertension will certainly benefit from an ACE inhibitor. Loop diuretics (e.g., furosemide) are not indicated for the primary treatment of hypertension in diabetics (or, really, anyone else). Angiotensin receptor blockers (ARBs) are a reasonable alternative in the hypertensive patient with albuminuria if an ACE inhibitor is not tolerated. Vasodilators and calcium-channel blockers are not optimal choices in this patient although nondihydropyridine calcium channel blockers (verapamil, diltiazem) are an option for renal protection in patients with worsening albuminuria especially in those who cannot tolerate an ACE inhibitor or ARB. "E," beta-blockers, should not be used first line for treating hypertension in patients without cardiac disease.
Question 10.10.6 Which of the following is NOT a side effect of ACE inhibitors?
Answer 10.10.6 The correct answer is "E." All of those listed—except cooties—are side effects of ACE inhibitors. Cooties are airborne parasites for which obnoxious 4th grade boys serve the main host. Hope you got your "cooties shot" when you were younger. If so, you should be fine.
Adverse effects of ACE inhibitors are due to either reduced angiotensin II formation or to increased kinin formation. Those related to reduced angiotensin II formation include hypotension, acute renal failure, hyperkalemia, and problems during pregnancy. Side effects thought to be related, at least in part, to increased kinins include cough, angioedema, and anaphylactoid reactions. Termination of the ACE inhibitor should be considered if hyperkalemia cannot be controlled or the serum creatinine concentration increases more than 30% above the baseline value within the first 6 to 8 weeks when blood pressure is reduced. Also, both ACE inhibitors and ARBs are contraindicated in pregnancy.
Guidelines published by JNC8 (2014) and the ADA (2015) endorse higher blood pressure goals for hypertensive diabetics than was the case in prior guidelines. The blood pressure target for most diabetic patients is now <140/90 mm Hg. A lower target (e.g., <130/80) may be appropriate for certain individual, such as younger patients, if it can be achieved without undue treatment burden.
After 3 months of dietary therapy and lifestyle modifications, the patient returns to see you with his husband. While he has been adherent to the recommendations given by you and the diabetes education staff, his HbA1c remains elevated at 7.9%. You decide to begin pharmacologic therapy.
Question 10.10.7 Which medication is the most appropriate first-line therapy for an obese patient with type 2 diabetes?
A) A thiazolidinedione ("glitazone" [e.g., Actos]).
B) A sulfonylurea (e.g., glipizide).
E) A dipeptidyl peptidase-4 inhibitor [DPP-4 or "gliptin" (e.g., Januvia)].
Answer 10.10.7 The correct answer is "D." Metformin does not cause weight gain (unlike most other treatments for diabetes), has evidence for reducing diabetes complications, and is inexpensive; thus, it is the drug of choice in most DM2 patients. In addition, it is well tolerated by most patients and has very little risk of hypoglycemia. Studies comparing effects on end-organ disease show better outcomes with metformin than with sulfonylureas. Thiazolidinediones known as "glitazones" ("A") are not first-line for several reasons, chief among these being the possibility of increased cardiovascular events (rosiglitazone and pioglitazone can exacerbate CHF). The track record of rosiglitazone is somewhat spotty: it was removed from the market due to an increase in cardiovascular events and then was reintroduced even though there was no additional safety data; avoid it if you can. Sulfonylureas ("B") are also effective and well-tolerated but have a significant risk for hypoglycemia and are associated with weight gain. All other oral drugs are best considered second-line agents. "E" is of special note. DPP-4 inhibitors, also known as "gliptins," block the degradation of the body's endogenous incretin, which helps to lower blood sugar. DPP-4 acts as a "glucagon-like peptid-1" (GLP-1). DPP-4 inhibitors (Sitagliptin–Januvia, saxagliptin—Onglyza, alogliptin–Nesina … see below for a caution) can be used as an "add-on" therapy if traditional hypoglycemic agents are not effective and have the benefit of some weight loss. In a patient with very poor control (e.g., A1c >9%) at diagnosis, insulin ("C") would be a potential first-line agent, but not in this patient whose is partially controlled.
New data suggests an association (or maybe causality) of congestive heart failure with saxagliptin (Onglyza) and alogliptin (Nesina). This does not seem to be a problem with sitagliptin (Januvia). These drugs only reduce HbA1c by about 0.5% and have no data demonstrating cardiovascular benefit. Other reported side effects include headache, nasopharyngitis, and upper respiratory tract infections. Also, acute pancreatitis has been reported in association with DPP-4 inhibitors, but currently there is insufficient evidence to determine a causal relationship.
Another class of "glucagon-like peptide-1" (GLP-1) drugs act as receptor agonists (e.g., exenatide—Byetta, liraglutide—Victoza, albiglutide—Tanzeum, etc.) which bind to the GLP-1 receptor. They are resistant to breakdown by the body and thus provide sustained glucose control. These are given by subcutaneous injection and are fairy costly but have the advantage of being more potent than the gliptins and may even cause weight loss in type 2 diabetics.
Question 10.10.8 Which of the following is NOT a side effect of GLP-1 receptor agonists (exenatide, liraglutide, albiglutide)?
Answer 10.10.8 The correct answer is "A." Actually, GLP-1 agonists may cause weight loss of 1.5 to 2.5 kg over 30 weeks. These drugs are associated with pancreatitis although rarely and the association is tenuous. Due to an association with thyroid cancer, their use is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or MEN 2A or 2B. The risk of hypoglycemia is small—but not zero—with GLP-1 agonists. Somewhere between 10% and 50% of patients may develop GI symptoms.
Question 10.10.9 Metformin should NOT be used in which class of patients?
B) Patients with impaired renal function.
C) Patients with leukemias or lymphomas.
D) Postmyocardial infarction patients with normal systolic function.
E) Patients with insufficient fat stores.
Answer 10.10.9 The correct answer is "B." Patients with renal disease are at a higher risk of lactic acidosis, the most severe complication of metformin therapy, although it is exceedingly rare (3 cases per 100,000 vs. 2 cases per 100,000 with other hypoglycemic agents). Current manufacturer recommendations state that metformin should be avoided if the serum creatinine ≥1.5 mg/dL in males and ≥1.4 mg/dL in females. However, metformin is likely safe to start as long as the GFR is >30 mL/min (max dose 1,000 mg/day for those with a GFR between 30 and 60 mL/min). Patients with pulmonary or neoplastic diseases may take metformin unless they also have severe hepatic or renal failure. CHF is a relative contraindication to the use of metformin; it is being used with increased frequency in stable, patients not at risk for hypoxemia. Use clinical judgment. Metformin should be held for 48 hours after contrast studies. Please refer to the general recommendations regarding anti-hyperglycemic therapy in type 2 diabetes by the ADA (Table 10-2).
TABLE 10-2RECOMMENDATIONS FOR MEDICAL TREATMENT DIABETES MELLITUS TYPE 2 ||Download (.pdf) TABLE 10-2 RECOMMENDATIONS FOR MEDICAL TREATMENT DIABETES MELLITUS TYPE 2
Question 10.10.10 Which one of the following is NOT a risk factor or prognostic marker for lower-extremity amputation in patients with diabetes?
B) Bony deformity of the feet or ankles.
C) C-reactive protein (CRP) level.
D) Abnormal monofilament testing for sensory function.
E) Severe nail pathology.
Answer 10.10.10 The correct answer is "C." The risk of ulcers or amputations is increased in patients who have had diabetes for 10 years or more, are male, have a history of poor glucose control, or have evidence of microvascular complications of diabetes (e.g., retinopathy). Bony deformities, loss of protective sensation, and severely dystrophic toenails are also risk factors for amputation. The Semmes–Weinstein 10 g monofilament sensory examination is the most sensitive neurologic test for predicting the future occurrence of a diabetic foot ulcer. An elevated CRP in and of itself is not a known risk factor for amputation, but CRP may be elevated if there is lower extremity infection present.
At the next visit, you review the patient's medical record and try to assure that he is up to date on his preventive health care.
Question 10.10.11 Which of the following is NOT true regarding preventive services in diabetics?
A) Patients diagnosed with type 2 diabetes should have a dilated eye examination at the time of diagnosis.
B) Patients with type 1 diabetes should have a dilated eye examination at the time of diagnosis if they are over age 12.
C) Check TSH annually in type 1 diabetes, in patients with dyslipidemia or diabetic women over age 50 years.
D) A urine microalbumin should be checked at least yearly in all type 2 diabetics.
E) A foot examination using a 10 g nylon microfilament should be done annually for all diabetics.
Answer 10.10.11 The correct answer is "B." Patients with diabetes type 1 should have an eye examination 3 to 5 years after the diagnosis and then yearly. Age at the time of diagnosis is not a factor in determining when an eye examination should be done. See Table 10-3 for components of recommended diabetes follow-up.
TABLE 10-3SUMMARY OF SCREENING RECOMMENDATIONS ||Download (.pdf) TABLE 10-3 SUMMARY OF SCREENING RECOMMENDATIONS
DM type 1:
Urine microalbumin starting at age 12 and then every 6 to 12 months.
Dilated eye examination 5 years after diagnosis and then annually.
HbA1c every 6 months for stable patients achieving glycemic goals, every 3 months for patients changing therapy or not meeting glycemic goals.
Blood pressure screening at every visit.
Foot examination and screening for polyneuropathy at diagnosis and annually.
If not performed/available within past year
Fasting lipid profile, including total, LDL, and HDL cholesterol and triglycerides, as needed
Serum creatinine and calculated glomerular filtration rate
TSH in type 1 diabetes, dyslipidemia, or women over age 50 years.
DM type 2: Same as DM1 above, except:
Question 10.10.12 Speaking of prevention, your patient, now 48 years old with his diabetes controlled, asks if he should be taking an aspirin daily to protect his heart. You respond:
A) "Take aspirin 325 mg daily because it will lower your risk of myocardial infarction."
B) "Diabetes does not automatically qualify you for aspirin therapy. Let's check your atherosclerotic cardiovascular disease (ASCVD) score."
C) "The risks and benefits of aspirin in your case are unknown."
D) "Take it by the truckload. I've got a lot of stock in Bayer."
Answer 10.10.12 The correct answer is "B." The ADA recommends considering aspirin therapy (75–162 mg/day) as a primary prevention strategy in those with type 1 or type 2 diabetes at increased cardiovascular risk (10-year risk ≥10%). Who would be in this category of risk? Most diabetic men aged >50 years or diabetic women aged >60 years who have at least one additional major risk factor (family history of cardiovascular disease, hypertension, smoking, dyslipidemia, or microalbuminuria). ADA recommends AGAINST aspirin use for CVD prevention for adults with diabetes at low CVD risk (10-year CVD risk <5%, such as in men aged <50 years and women aged <60 years with no major additional CVD risk factors) since the potential adverse effects from bleeding likely offset the potential benefits. If you decide to prescribe aspirin for primary CVD prevention in a diabetic, use 81 mg daily.
Unfortunately, this patient follows the "rule" of type 2 diabetes and ends up on multiple medications. When he returns to your clinic a few months later, he is complaining of shortness of breath and lower extremity edema. You decide to follow the "rule" of blaming drugs first…
Question 10.10.13 Which of the following drugs (by itself—not in combination with other drugs) is the most likely cause of this patient's edema, shortness of breath, and possible heart failure?
Answer 10.10.13 The correct answer is "C." The thiazolidinediones ("glitazones") tend to cause edema as one of their major side effects. Thus, they are contraindicated in patients with a history of heart failure. Some drug combinations can cause edema, including the combination of glimepiride and metformin.
Because of the problem with edema, you decide to change this patient to a sulfonylurea, and you choose to start glyburide. The patient does well on this for several weeks but is then found unconscious in his home with a blood sugar of 20 mg/dL. Strike two, doc! He is rapidly revived by the paramedics with an amp of D50. You are called to see the patient in the ED. He is currently awake, conversant, and eating ("a great excuse for a couple of cookies!"). He would like to go home since he is back to his baseline.
Question 10.10.14 Which of the following is the best next step in the management of this patient's hypoglycemic episode?
A) Discharge the patient from the ED and have him continue his regimen, including glyburide.
B) Discharge the patient from the ED and have him stop his glyburide and start insulin.
C) Admit the patient and start him on IV dextrose 5% infusion.
D) Admit the patient and observe him for 24 hours.
E) Give him a gift card to local casino buffet, and tell him, "Pretend it's your birthday!"
Answer 10.10.14 The correct answer is "D." Patients on an oral hypoglycemic agent—especially longer-acting agents like glyburide—should be admitted for observation. It would be reasonable to let him eat, check his glucose periodically, and hold his diabetic medications. He is currently stable and does not appear to need IV dextrose ("C"), but the patient should have IV access, and a half- or full-ampule of D50 can be given if necessary. The absorption of oral hypoglycemic agents is somewhat erratic, and their effect can be prolonged. The patient may have an additional episode of hypoglycemia for up to 36 to 48 hours after the initial episode. This is not true of patients on insulins (NPH or short-acting insulin [e.g., regular, lispro]), who may be discharged from the ED after a few hours. But for this patient, discharge from the ED ("A," "B," and "E") would be unwise.
15 to 20 g of fasting-acting carbohydrate like glucose tablets, honey, corn syrup, nonfat or 1% milk, jellybeans, gumdrops, gel tube, raisins, hard candy, regular soda, sweetened fruit juice can be used to treat symptomatic hypoglycemia. For severe hypoglycemia, glucagon injection may be needed. Glucagon, 1 mg IM or IV, is another option.
The following medications generally do not cause hypoglycemia: metformin, acarbose, dipeptidyl peptidase (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists.
It turns out that one of your partners has started this patient on a beta-blocker for its cardioprotective and antihypertensive effects while you were on vacation. The patient wants to know if this may have prevented him from noticing the signs and symptoms of hypoglycemia.
Question 10.10.15 Your response is:
A) "Beta-blockers reduce your ability to recognize hypoglycemia and the drug should be stopped."
B) "Beta-blockers reduce your ability to recognize hypoglycemia but the benefits are worth it."
C) "Beta-blockers do not decrease your ability to recognize hypoglycemia to any great degree. Don't worry about it."
D) "ACE inhibitors are better drugs because they do not contribute to hypoglycemia in diabetics."
Answer 10.10.15 The correct answer is "C." Beta-blockers do not significantly interfere with patients' ability to recognize hypoglycemia. The main thing that contributes to unawareness of hypoglycemia in diabetics is the rate of glucose drop (a slow drop is less likely to be noticed) and autonomic insufficiency (patients cannot respond with tachycardia, sweating, etc., to the outpouring of adrenergics). "D" is incorrect. ACE inhibitors, like beta-blockers, are actually associated with hypoglycemia in diabetics.
The ADA recommends the target A1c in nonpregnant adults with diabetes be <7%. However, it also advises more or less stringent glycemic goals may be appropriate for individual patients and goals should be individualized on the basis of duration of diabetes, age/life expectancy, comorbid conditions, known CVD or advanced microvascular complications, hypoglycemia unawareness, and individual patient considerations. For patients with multiple comorbidities and higher risks for hypoglycemia and other drug adverse effects, a higher A1c, even up to 8.5%, may be acceptable (but try telling that to the insurance companies).
You admit the patient and advise him to carry a source of glucose with him at all times and everybody has a happy outcome until…
The patient has developed persistent hyperglycemia despite being on maximal doses of metformin and glyburide. He is willing to begin insulin therapy, but wants to give himself as few injections as possible.
Question 10.10.16 Which of the following regimens would be best for him?
A) A single injection of insulin glargine (LantusTM) or NPH insulin at bedtime.
B) A single injection of 70/30 NPH/regular insulin at bedtime.
C) A baseline bedtime injection of insulin glargine and up to three injections of short-acting insulin with meals.
D) Regular insulin with meals to control post-prandial blood sugars.
Answer 10.10.16 The correct answer is "A." Because of its slow release, insulin glargine provides a steady-state insulin level throughout 24 hours and is less likely to cause nocturnal hypoglycemia. Other options include insulin detemir and ultralente insulin (off the market in the United States), or bedtime NPH, all of which have a prolonged action. Regular insulin (as found in 70/30) is generally not the place to start with type 2 diabetics ("B"). Multiple daily insulin injections may be necessary for type 1 diabetics, but rarely are so for type 2 patients. For DM2, long-acting insulin is usually started first and bolus mealtime insulin added later, so "C" would not be the first choice. As noted as above, regular insulin ("D") isn't the place to start in DM 2. If you are trying to start with the simplest possible regimen, choose something like "A."
Sulfonylureas and insulin work in the same manner: they both increase circulating insulin levels. For this reason, some choose not to use these two drugs together and will taper the sulfonylurea after the patient is on a stable dose of insulin.
Your patient is hospitalized for acute diverticulitis and requires urgent partial colectomy.
Question 10.10.17 Which of the following statements regarding the management of diabetes in hospitalized patients is TRUE?
A) Hyperglycemia in the hospital has minimal if any effect on outcomes of myocardial infarction.
B) A standardized sliding-scale insulin regimen is adequate to control hyperglycemia in all hospitalized diabetic patients.
C) Insulin requirements will be lower for acutely ill, hospitalized diabetic patients.
D) Metformin should be discontinued in seriously ill, hospitalized patients.
Answer 10.10.17 The correct answer is "D." In general, one should consider discontinuation of metformin in severely ill, hospitalized patients due to the possible need for contrast studies, changes in fluid balance, changes in glomerular filtration rate, etc. "A" is incorrect. Hyperglycemia is associated with worse outcomes in hospitalized patient with cardiac disease and those who are in an intensive care unit for most reasons. But this may be because elevated blood sugars suggest they are under greater metabolic stress and sicker to begin with. "B" is also incorrect. Sliding-scale regimens, if used at all, should be individualized to each patient, rather than prescribed as a standardized regimen. It has become clear that a sliding scale is not the best way to control blood sugars in hospitalized patients. Continuing some type of "normal" insulin regimen is best, using supplemental insulin as needed. In hospitalized patients, it is generally recommended to discontinue oral antidiabetic agents and control the glucose using insulin only, provided in a combination form including basal long acting insulin plus pre-meal short acting insulin if on diet and correctional insulin (aka basal/bolus insulin). The stress of acute illness and surgery will likely increase insulin requirements in most diabetics, not decrease them.
Chasing the glucose in an attempt to maintain tight control in the hospital is counterproductive and does not improve outcomes! Even though patients with hyperglycemia may do worse, it is clear that the elevated glucose is a marker for metabolic stress which is why outcomes might be worse…they are sicker to begin with. Thus for sicker patients, aim for a blood sugar of between 120 and 180 mg/dL. This has been found to be superior to more intensive glycemic control.
He does well and is ready for discharge. He asks about self-monitoring of blood glucose.
Question 10.10.18 How often should a type 2 diabetic on oral hypoglycemic agents measure his or her blood glucose?
A) Once or twice a week, at varying times during the day.
B) Four times daily—before meals and at bedtime.
C) Twice daily—fasting and 2 hours after a meal.
D) Once or twice daily—fasting and before a meal.
E) Routine blood sugars are not indicated on a daily basis for type 2 diabetics.
Answer 10.10.18 The correct answer is "E." Daily measurements of finger stick sugars in patients on oral hypoglycemic agents do nothing to improve glycemic control (BMJ. 2012 Feb 27;344:e486). In these patients, we are not reacting to daily fluctuations in glucose control but rather making changes in response to the HbA1c. Occasional random sugars are not unreasonable to get a general idea about glycemic control. Type 2 diabetics on insulin (and all type 1 diabetics) should measure their blood glucose at least daily, and ideally two or three times per day, regardless of the presence or absence of symptoms. The patient has come back to your clinic several times for follow-up, and his current medications including metformin and glyburide are adjusted to their maximum doses. The patient is not interested in injectable medication—he changed his tune from earlier after reading online how he might get addicted to insulin. You discuss adding a third oral agent, and muster an expression that belies enthusiasm.
THE NEW KID ON THE BLOCK: Another class of diabetic medication is the sodium-glucose co-transporter 2 (SGLT2) inhibitors, which include canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance). They promote the renal excretion of glucose (literally peeing out the sugar) and thereby modestly lower elevated blood glucose levels in patients with type 2 diabetes. SGLT2 inhibitors lower A1c levels by 0.5% to 0.7%, limited by the filtered load of glucose and the osmotic diuresis that is caused by this therapy. The glucose-lowering effect is independent of insulin (beta cell function and insulin sensitivity). The overall benefits of SGLT2 inhibitors include a decrease in blood pressure and weight and a low incidence of hypoglycemia. The side effects are exactly what you would think given the mechanism of action is to pee out sugar: vulvovaginal candidiasis, urinary frequency, and urinary tract infection. LDL goes up 4% to 8%. Also, the FDA has issued a warning regarding ketoacidosis. There is also some concern about an association with bladder cancer that requires further post-market monitoring. If there is a "line" for these drugs, it's third-line.
The patient's diabetes is not optimally controlled and he develops diabetic neuropathy years later.
Question 10.10.19 Which of the following agents is LEAST effective in treatment of diabetic neuropathic pain?
A) Tricyclic antidepressants.
C) Duloxetine (Cymbalta).
E) Venlafaxine (Effexor XR).
Answer 10.10.19 The correct answer is "B." Several drugs have been approved specifically for relief of diabetic peripheral neuropathic pain in the United States (pregabalin, duloxetine, and tapentadol), but none affords complete relief, even when used in combination. Venlafaxine, amitriptyline, gabapentin, valproate, and other opioids (morphine sulfate, tramadol, controlled release oxycodone) may be effective and may be considered for treatment of painful diabetic peripheral neuropathy. Low-dose tricyclic antidepressants are the most effective of this group (e.g., nortriptyline or amitriptyline 25 mg qhs) but also have anticholinergic side effects (Lancet Neurol. 2015 Feb; 14:162). Tricyclics and gabapentin are additive, so consider using them together if needed). Remember that gabapentin causes weight gain, something these patients don't need. For the treatment of neuropathic pain, TCA>strong opiates>tramadol>SNRIs>pregabalin>gabapentin. SSRIs are generally ineffective for neuropathic pain.
Well LA-DI-DA (well, LADA, anyway). LADA stands for latent autoimmune diabetes in adults. This is a patient who clinically starts as a patient with DM2 but also has circulating anti-islet cell and/or anti-GAD antibodies. As some point in their disease, these adult patients lose enough pancreas to convert to a type 1 diabetic. These are patients who initially respond to noninsulin hypoglycemic agents (metformin, sulfonylureas, etc.) but eventually no longer respond to these drugs and become insulin dependent. This may represent up to 10% of the DM 2 population.
Objectives: Did you learn to…
Recognize diagnostic criteria for diabetes?
Differentiate diabetes type 1 from type 2?
Evaluate a patient with new onset type 2 diabetes?
Identify risk factors for complications of diabetes?
Initiate and manage oral therapy in type 2 diabetes?
Start a type 2 diabetic patient on insulin?
Manage diabetes in the hospital setting?
Treat of painful diabetic peripheral neuropathy?