American College of Physicians: Internal Medicine — Doctors for Adults ®

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ACP DiabetesMonthly



In the News for the month of November 2013




Highlights

Diabetes raises coronary artery disease risk more in women under 60

Young and middle-aged women with diabetes have about 4 times the risk of coronary artery disease as same-age women without diabetes and similar risk to same-age diabetic men, an analysis found. More...

CABG and PCI offer similar improvements in quality of life for diabetics

In patients with diabetes, coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with drug-eluting stents improved health status and quality of life to similar degrees. More...

eGFR overestimates kidney function in patients with poor glycemic control

Poor glycemic control causes overestimations in calculations of estimated glomerular filtration rate (eGFR), according to a recent study that developed a formula to correct the problem. More...


Test yourself

MKSAP Quiz: Elderly patient with episodes of confusion

This month's quiz asks readers to evaluate an 82-year-old with a 6-year history of type 2 diabetes mellitus and a 5-year history of heart failure. More...


From ACP InternistWeekly

ADA updates nutrition guidelines to address varied eating patterns

The American Diabetes Association (ADA) recently released new recommendations on nutrition therapy for adults with type 1 or type 2 diabetes. More...

ACE inhibitors may be better than other antihypertensives for diabetes patients

Angiotensin-converting enzyme (ACE) inhibitors were found to possibly improve outcomes for patients with diabetes more than other antihypertensives, a recent meta-analysis found. More...


From ACP Journal Club

Review: Bariatric surgery improves weight and glycemia in nonmorbidly obese adults with diabetes

A review of 3 randomized controlled trials found that surgical treatment increased weight loss and improved diabetes-related outcomes more than nonsurgical treatment in moderately obese patients. More...

A lifestyle intervention did not reduce cardiovascular outcomes in overweight or obese patients with type 2 diabetes

The Look AHEAD trial randomized more than 5,000 overweight and obese type 2 diabetics to intensive lifestyle intervention or diabetes support and education and found that the intensive group reduced several risk factors, but not the primary outcome. More...


Tool of the month

Advice for patient education about exercise

When counseling patients with type 2 diabetes about their exercise habits, consider some advice from ACP Smart Medicine and ACP DiabetesMonthly's physician editor. More...


Keeping tabs

Spotlight on lifestyle change

The effects of lifestyle interventions on patients with diabetes were analyzed by several recent studies. More...


Physician editor: David V. O'Dell, MD, FACP



Highlights


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Diabetes raises coronary artery disease risk more in women under 60

Young and middle-aged women with diabetes have about 4 times the risk of coronary artery disease (CAD) as same-age women without diabetes and similar risk to same-age diabetic men, an analysis found.

Researchers analyzed data on men and women younger than 60 who didn't have CAD at enrollment and whose diabetes was determined by physician report, use of hypoglycemic medication, and/or fasting glucose of at least 126 mg/dL. Subjects came from the GeneSTAR Study (n=1,448), the Multi-Ethnic Study of Atherosclerosis (MESA; n=3,072) and the National Health and Nutrition Examination Survey III (NHANES III) Mortality Follow-up Study (n=6,997). Follow-up ranged from 7 to 15 years. The main outcome was fatal CAD in NHANES III and any CAD event in the other 2 studies. Results were published online Oct. 31 by Diabetes Care.

After adjustment for age, race and education, women with diabetes had a CAD event rate roughly 4 times higher than that of women without diabetes (adjusted hazard ratio, 4.23; P>0.01). The presence of diabetes didn't change the risk of CAD for men, however. Among people without diabetes, CAD event rates were lower for women than men (P<0.001 in GeneStar and Mesa; P=0.07 in NHANES). After adjustment for smoking, body mass index, hypertension, HDL and non-HDL cholesterol, and use of antihypertensive and cholesterol-lowering medication, the hazard ratio of CAD was 2.43 (95% CI, 1.76 to 3.35) in men versus women without diabetes and 0.89 (95% CI, 0.43 to 1.83) for men versus women with diabetes (interaction by diabetes status, P=0.01).

Diabetes "equalized rates of CAD by gender," the researchers concluded, by conferring a much higher CAD risk on women than men. A novel finding in this study was that the elevated risk for women applied to otherwise healthy young and middle-aged women, not just elderly women, they added. The finding that men had no elevated CAD risk with diabetes may be explained by an earlier incidence of CAD in men in general: "Male gender may represent an early CAD risk factor that 'borrows' from the future, potentially comparable to the CAD risk observed for women later in life," the authors wrote.

Current clinical guidelines advise an earlier start to cardiovascular prevention strategies for men than women with diabetes, and these should perhaps be revised, the authors wrote. "Aggressive preventive strategies may be as important for younger women with diabetes as they are for men," they wrote.


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CABG and PCI offer similar improvements in quality of life for diabetics

In patients with diabetes, coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with drug-eluting stents improved health status and quality of life to similar degrees.

Researchers randomized 1,880 diabetic patients (935 CABG, 945 PCI) from 18 countries with multivessel coronary artery disease (CAD) to undergo either CABG surgery or PCI between 2005 and 2010. This prospective substudy of the FREEDOM trial assessed patient health via the Seattle Angina Questionnaire (SAQ) for angina frequency, physical limitations, and quality-of-life scores at baseline, at 1, 6, and 12 months, and then annually. (Scores range from 0 to 100, with higher scores indicating better health.) Results appeared in the Oct. 16 Journal of the American Medical Association.

At 1 month after surgery, PCI patients showed more improvement than CABG patients on the physical limitations score, with a mean difference between CABG and PCI of −8.1 points (95% CI, −9.9 to −6.3 points; P<0.001). PCI patients also showed some greater improvement on the quality-of-life subscale, with a mean difference between CABG and PCI of −1.9 points (95% CI, −3.6 to −0.2 points; P=0.03).

At 6 months, scores for the quality-of-life subscale were similar for the 2 treatment groups, although the physical limitations score modestly favored PCI. At 1 year, patients in the CABG group had better scores on physical limitations (mean difference between CABG and PCI, 2.0 points; 95% CI, 0.4 to 3.6 points; P=0.01) and quality of life (mean difference between CABG and PCI, 1.9 points; 95% CI, 0.4 to 3.4 points; P=0.01).

At 2-year follow-up, there was significantly greater benefit of CABG on each domain (mean treatment benefit, 1.3 points [95% CI, 0.3 to 2.2 points] for angina frequency, 4.4 points [95% CI, 2.7 to 6.1 points] for physical limitations, and 2.2 points [95% CI, 0.7 to 3.8 points] for quality of life; P<0.01 for each comparison). Beyond year 3, there were no consistent between-group differences for the 3 SAQ subscales, although there were significant differences in favor of CABG at 5 years for the physical limitations and quality-of-life subscales.

Researchers noted that the FREEDOM trial has already shown a significant benefit of CABG over PCI for the composite end point of death, myocardial infarction, or stroke among diabetic patients with multivessel CAD, especially patients with the most severe angina at baseline. They also noted that the differences in scores found in this study were small enough that they may not be clinically significant.

The study authors concluded that, based on these results, either treatment provides "substantial and sustained benefits on cardiovascular-specific health status and quality of life" but that previous research shows that CABG should be strongly preferred as the initial revascularization strategy. "[H]owever, some patients who do not wish to face these acute risks [associated with a CABG] may still choose the less invasive PCI strategy. For such patients, our study provides reassurance that there are not major differences in long-term health status and quality of life between the 2 treatment strategies."


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eGFR overestimates kidney function in patients with poor glycemic control

Poor glycemic control causes overestimations in calculations of estimated glomerular filtration rate (eGFR), according to a recent study that developed a formula to correct the problem.

The study included 40 patients with diabetes and 40 patients without diabetes, all of whom had their GFR evaluated by inulin clearance. Their eGFRs were also calculated using serum creatinine and serum cystatin C and both measures together. Researchers found that patients with and without diabetes did not significantly differ in their inulin clearance, but they did have significant differences on all 3 of the eGFR results. The diabetic patients had significantly higher eGFRs than the nondiabetic patients. Results were published early online by Diabetes Care on Oct. 15.

After analyzing various factors, the researchers found that patients with higher hemoglobin A1c (HbA1c) and glycated albumin levels had greater inaccuracy in their eGFRs. They then developed equations to use these factors to correct the overestimations. Testing showed that their new equations (which used measurements of creatinine or cystatin C and HbA1c or glycated albumin) improved eGFR calculation for all patients, but especially those with diabetes. The formula to correct eGFR using HbA1c and creatinine (the measures most commonly available in clinical practice) is eGFR (based on creatinine) divided by (0.428 + 0.085 × HbA1c).

This new formula is a clinically useful and feasible way to more accurately calculate the eGFR of patients with diabetes and kidney disease, the study authors concluded. Overestimations of renal function using the current formulas could delay needed treatment for diabetic patients, especially those with poor glycemic control, they added. The authors noted that the study was limited by its small size and use of a single center, so the results should be confirmed in larger studies. Future research should also construct formulas like this one for different races, the authors recommended.



Test yourself


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MKSAP Quiz: Elderly patient with episodes of confusion

An 82-year-old woman is evaluated for the recent development of frequent episodes of confusion and forgetfulness. She has a 6-year history of type 2 diabetes mellitus and a 5-year history of heart failure. Medications are glyburide, furosemide, lisinopril, and potassium supplements.

mksap.gif

On physical examination, temperature is normal, blood pressure is 142/77 mm Hg, pulse rate is 87/min, and respiration rate is 16/min; BMI is 20. All other physical examination findings are unremarkable, including those from a mental status examination.

Laboratory studies show a serum creatinine level of 1.3 mg/dL (115 µmol/L) and a hemoglobin A1c value of 6.2%.

Which of the following is the most appropriate immediate next step in management?

A. Discontinue glyburide
B. Start glipizide
C. Start metformin
D. Start premixed 70/30 insulin (neutral protamine Hagedorn [NPH] insulin/regular insulin)

Click here or scroll to the bottom of the page for the answer and critique.


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From ACP InternistWeekly


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ADA updates nutrition guidelines to address varied eating patterns

The American Diabetes Association (ADA) recently released new recommendations on nutrition therapy for adults with type 1 or type 2 diabetes.

The recommendations, which were published by Diabetes Care on Oct. 9 and replace a set issued in 2008, note that "there is not a 'one-size-fits-all' eating plan for individuals with diabetes." In general, diabetes patients should eat a variety of nutrient-dense foods in appropriate portion sizes, with diet specifics individualized based on their personal and cultural preferences, health literacy and numeracy, access to food and willingness and ability to change. Both medical nutrition therapy and diabetes self-management education are recommended by the guidelines for patients with either type of diabetes.

The recommendations also included the following advice:

  • Evidence has not determined an ideal percentage or quantity of carbohydrates, protein or fat that patients with diabetes should consume, so choices should be individualized. Monitoring carbohydrate intake is key to achieving glycemic control, however.
  • Patients with diabetes should follow the same nutritional guidelines as the general public with regard to consumption of fiber and whole grains, foods containing long-chain omega-3 fatty acids, saturated and trans fats, sodium and cholesterol.
  • A Mediterranean-style diet is an effective alternative to a lower-fat, higher-carbohydrate eating pattern.
  • Substituting low-glycemic load foods for high-glycemic load foods may modestly improve glycemic control.
  • Patients with diabetes should limit or avoid sugar-sweetened beverages and drink alcohol only in moderation (1 drink per day for women, 2 for men).
  • There is no clear evidence to support supplementation with vitamins, minerals, omega-3, or cinnamon and other herbs for patients with diabetes.
  • For overweight or obese adults with type 2 diabetes, reducing energy intake while maintaining a healthful eating pattern is recommended to promote weight loss.

The recommendations also include specific advice on coordinating food with different types of diabetes medications. The authors called for additional research on a number of topics, including Mediterranean-style, low-glycemic index and low-carbohydrate diets, as well as the effects of nonnutritive sweeteners.

"Nutrition interventions should emphasize a variety of minimally processed nutrient-dense foods in appropriate portion sizes as part of a healthful eating pattern and provide the individual with diabetes with practical tools for day-to-day food plan and behavior change that can be maintained over the long term," the recommendations concluded.


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ACE inhibitors may be better than other antihypertensives for diabetes patients

Angiotensin-converting enzyme (ACE) inhibitors were found to possibly improve outcomes for patients with diabetes more than other antihypertensives, a recent meta-analysis found.

In the systematic review and Bayesian network meta-analysis, researchers included 63 randomized, controlled trials with more than 36,000 participants who all had diabetes. All of the studies had follow-up of at least a year and reported outcomes of all-cause mortality, need for dialysis or doubling of serum creatinine. Studied drugs included ACE inhibitors, angiotensin receptor blockers (ARBs), alpha-blockers, beta-blockers, calcium channel blockers and diuretics. Results were published by BMJ on Oct. 24.

Of the studied drugs, only ACE inhibitors significantly reduced the risk of serum creatinine doubling compared to placebo (odds ratio, 0.58; 95% credible interval, 0.32 to 0.90). Only beta-blockers significantly increased patients' mortality risk (odds ratio, 7.13; 95% credible interval, 1.37 to 41.39). The researchers also looked at the drug classes compared to each other individually, and found that, although the differences were not statistically significant, ACE inhibitors had a probability of being superior to ARBs on all three outcomes.

The effect of combination therapy on mortality risk was also examined. Although no combination significantly outperformed placebo on this outcome, the analysis found that an ACE inhibitor plus a calcium channel blocker had the greatest probability (73.9%) of being the best treatment to reduce mortality, followed by ACE inhibitor plus diuretic at 12.5%, ACE inhibitors at 2.0%, calcium channel blockers at 1.2% and ARBs at 0.4%.

The results show superior effects with ACE inhibitors compared to other hypertension treatments for diabetic patients, the researchers concluded. Especially considering the lower cost of these drugs, they should be the first-line choice. If adequate control is not achieved with ACE inhibitors alone, adding a calcium channel blocker might be the preferred treatment, the authors recommended.

They cautioned that the number of patients in the trials prohibited evaluation of some other combination therapies (including ARBs plus any of the other drug classes), and that only 1.7% of the studied patients took an ACE inhibitor plus a calcium channel blocker, so the generalizability of that finding is uncertain. Future research should further compare ACE inhibitors and ARBs, they said, noting that some guidelines suggest that their effects are equivalent.



From ACP Journal Club


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Review: Bariatric surgery improves weight and glycemia in nonmorbidly obese adults with diabetes

A review of 3 randomized controlled trials, including 290 moderately obese patients with diabetes or glucose intolerance, found that surgical treatment increased weight loss and improved diabetes-related outcomes at 24 months more than nonsurgical treatment in patients with body mass indexes of 30 to 35 kg/m2.

The study was published in the June 5 Journal of the American Medical Association. A summary of the study was published in the June ACP DiabetesMonthly. The following commentary by Raj Padwal, MD, MSc, was published in the ACP Journal Club section of the Oct. 15 Annals of Internal Medicine.

Bariatric surgery is the most effective treatment currently available for reducing weight and improving obesity-related comorbid conditions. Diversionary procedures (including gastric bypass and biliopancreatic diversion) are particularly effective for type 2 diabetes because they appear to improve glycemic control independent of weight loss. Enhanced secretion of enteric hormones, including incretins, may mediate these additional benefits. Glycemic control improves to the greatest extent in diet-controlled diabetes of short duration.

Widely used eligibility criteria for bariatric surgery endorse surgery for medically refractory patients with BMI 35.0 to 39.9 kg/m2 and a major obesity-related comorbidity or BMI ≥ 40 kg/m2. These arbitrarily set cutpoints have been criticized for being restrictive and lacking evidence. Surgery in patients with diabetes and BMI between 30 to 35 kg/m2 seems to be justified given the results of the review by Maggard-Gibbons and colleagues.

The decision to perform surgery in any patient must balance known risks and benefits and limitations of current evidence. Trials were relatively short and not designed to assess microvascular complications, macrovascular disease, or long-term mortality. Effects of long-term nutrient deficiencies require further study. Durability of diabetes remission must be clarified; recent studies suggest that only 65% of patients remain in remission after 5 years. Future studies are required to address these knowledge gaps and clarify the risk–benefit profile of surgery in patients with type 2 diabetes.


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A lifestyle intervention did not reduce cardiovascular outcomes in overweight or obese patients with type 2 diabetes

The Look AHEAD trial randomized more than 5,000 overweight and obese type 2 diabetics to intensive lifestyle intervention (ILI) or diabetes support and education (DSE) and found that the intensive group reduced weight, hemoglobin A1c (HbA1c) and some cardiovascular (CV) risk factors, but not the primary outcome of CV-related death, myocardial infarction, stroke or angina hospitalization.

The study was published in the July 11 New England Journal of Medicine. The following commentary by Donald A. Smith, MD, MPH, FACP, was published in the ACP Journal Club section of the Oct. 15 Annals of Internal Medicine.

There are many possible reasons that the superb trial by the Look AHEAD research group found no reduction in CV ischemic events at 10 years, a finding that conflicts with the results of at least 1 previous observational study. For example, the DSE group steadily lost 4 kg over 10 years. The initial 7-kg between-group difference in weight in the first year was not maintained and was reduced to approximately 2.5 kg over the final 5 years. Accordingly, differences between the ILI and DSE groups in HbA1c (7.33% vs. 7.44%) and systolic blood pressure (126 vs. 127 mm Hg) over the course of the study were small.

Further, mean baseline low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides already met Adult Treatment Panel III lipid guidelines. Baseline statin use (44% in both groups) increased less in the ILI group (71% vs. 74% at 10 y), producing LDL cholesterol levels that were 1.2 mg/dL lower in the DSE group than in the ILI group over 10 years. On the other hand, identical baseline HDL cholesterol levels of 43.5 mg/dL increased to 48.7 vs. 47.8 mg/dL in the ILI and DSE groups, respectively.

Although a significant effect might have been seen with longer follow-up or more aggressive and persistent weight loss, the benefits are unlikely to approach those seen with the potent risk factor–lowering medications currently available. The results of Look AHEAD suggest that, rather than expecting CV event reduction, patients with obesity and diabetes should make lifestyle changes for the important quality-of-life benefits already reported in this trial.



Tool of the month


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Advice for patient education about exercise

When counseling patients with type 2 diabetes about their exercise habits, consider this advice:

  • Individualize exercise regimen to the patient.
  • Caution patients regarding hypoglycemia during and after exercise.
  • For those patients who can exercise, consider beginning with 15 minutes of low-impact aerobic exercise 3 times per week with the aim of eventually achieving accumulative exercise of 150 minutes per week.

This content is from ACP Smart Medicine, the College's new Web-based clinical decision support tool developed specifically for internal medicine physicians. Information about ACP Smart Medicine is online.

Commentary from ACP DiabetesMonthly's physician editor:

Recently, a patient with type 2 diabetes asked me, "Do I need to continue to exercise?" He had read about recent trials that failed to show the benefit of exercise in preventing complications in established diabetics and was hoping I would back off on my routine questions about his exercise habits. While I acknowledged the accuracy of his report, I responded with an unequivocal "Absolutely!" These trials have been disappointing in terms of decreasing cardiovascular end points in mature diabetics, but we need to ensure our patients do not get the wrong impression from media reports. In the general population, the evidence supporting the benefits of routine exercise is overwhelming both in terms of mortality benefit and quality of life.

I have been making a point to routinely review the proven benefits of exercise with my prediabetic and diabetic patients, including:

  • the incontrovertible evidence that exercise decreases diabetes risk,
  • the clear benefits of exercise in improving insulin sensitivity and easing diabetes management, and
  • the proven ability of exercise to decrease blood glucose levels.

On this last point, I directly discuss the advice given to patients with type 1 diabetes a generation ago that exercise was contraindicated in hyperglycemia and explain that this just doesn't apply to type 2 disease. In fact, when a type 2 diabetic has an elevated blood glucose level, I strongly recommend exercise, such as a walk, to help bring blood glucose closer to target. I also remind type 2 diabetics to carry some form of sugar (hard candy, glucose tablets, raisins) in the unlikely event that hypoglycemia develops.

Other common questions I encounter during this conversation include "Does it matter what type of exercise I do?" "Does it have to be aerobic/cardiovascular?" "Does weightlifting count?" "Do I have to go to the gym?" and, finally "Does the exercise have to be all at one time or do short bursts count?" My interpretation of the literature is that any activity is better than none. Yes, mowing the lawn, walking the dog and even chasing grandkids in the park count. I often find myself trying to come up with creative ways to allow and encourage any activity in my patients, especially diabetics.

To sum up, while the recent trials have not been able to demonstrate conclusively that relatively short-term exercise (a few years) helps, embracing physical activity is clearly in our patients' best interests. So keep them moving!



Keeping tabs


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Spotlight on lifestyle change

The effects of lifestyle interventions on patients with diabetes were analyzed by several recent studies.

A meta-analysis in the Oct. 15 Annals of Internal Medicine looked at 9 randomized, controlled trials of lifestyle interventions (exercise, diet and at least 1 other component) in patients at risk for diabetes and 11 trials that included patients with diabetes. Overall, the interventions decreased the incidence of diabetes in at-risk patients, but for patients who already had the disease, researchers found no reduced risk of mortality and insufficient data to show any cardiovascular benefit. The finding of benefit from preventive interventions is encouraging, but the lack of effect on diabetic patients is of unclear clinical significance, the authors said.

In contrast, a large cohort analysis of more than 6,000 diabetics and 250,000 nondiabetics, published in the October Diabetologia, found similar benefits from following a healthy lifestyle in both groups, with patients with diabetes seeing a slightly greater benefit from healthy eating. The researchers looked at the impact of body mass index, waist/height ratio, food groups eaten, alcohol, physical activity and smoking on mortality. The diabetics and nondiabetics saw similar benefits from healthy choices, except that diabetics saw more reduction in their mortality risk from eating fruit, legumes, nuts, seeds, pasta, poultry and vegetable oil (and more increase in mortality from consuming butter and margarine). The results support recommending the same lifestyle advice to patients with and without diabetes, the authors concluded.

Another analysis, published by Diabetic Medicine Oct. 21, looked at how much newly diagnosed diabetes patients improved their diets. The 736 British patients had their diets, plasma vitamin C levels and cardiovascular disease risk assessed at baseline and 1 year. The patients reported significant reductions in energy, fat and sodium intake and increases in fruit, vegetable and fiber intake over the year. Patients whose reports of fruit intake were supported by a higher plasma vitamin C level had reductions in cardiovascular risk factors, while those who reduced fat, calorie and sodium intake also had improved hemoglobin A1c, waist circumference and cholesterol levels, even after researchers controlled for physical activity and medication changes. The authors concluded that dietary change may help reduce cardiovascular risk in newly diagnosed patients.


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MKSAP Answer and Critique



The correct answer is A. Discontinue glyburide. This item is available to MKSAP 16 subscribers as item 53 in the Endocrinology section. Information about MKSAP 16 is available online.

This patient should stop taking glyburide immediately. She has impaired kidney function and heart failure, both of which significantly impair her ability to clear glyburide and glyburide metabolites from her body. The biologic half-life of glyburide is thus prolonged. Because of this long half-life and the degree of this patient's kidney impairment (estimated glomerular filtration rate <50 mL/min/1.73 m2), merely decreasing her glyburide dosage is insufficient to reliably decrease blood drug levels and prevent the return of hypoglycemia. A hemoglobin A1c value of 6.2% is dangerously low in an older patient with diabetes mellitus and has most likely resulted in frequent episodes of hypoglycemia. These episodes, in turn, have caused her recent episodes of confusion and forgetfulness. Because it may take several days after discontinuation for the glyburide to decrease to undetectable levels, evaluating her plasma glucose level in 2 weeks would be appropriate as a next step in management.

Although glipizide is safer and has a shorter half-life than glyburide, it also accumulates in patients with chronic kidney disease. More importantly, no hypoglycemic agent (glipizide, metformin, or insulin) should be given to this patient until glyburide is completely cleared from her body, which would completely end the cycle of recurrent hypoglycemic episodes.

Key Point

  • Sulfonylureas with long half-lives, such as glyburide, should not be used in older patients with type 2 diabetes mellitus and impaired kidney function or heart failure.

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Test yourself

A 72-year-old woman is evaluated during a routine examination. She has very severe COPD with multiple exacerbations. She has dyspnea at all times with decreased exercise capacity. She does not have cough or any change in baseline sputum production. She is adherent to her medication regimen, and she completed pulmonary rehabilitation 1 year ago. She quit smoking 1 year ago. Her medications are a budesonide/formoterol inhaler, tiotropium, and an albuterol inhaler as needed. Following a physical and pulmonary exam, what is the most appropriate next step in management?

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