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

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ACP DiabetesMonthly



In the News for the month of August 2013




Highlights

Aggressive glucose control may not improve micro-, macrovascular outcomes in type 2 diabetes

Aggressive glucose control strategies yielded mixed results for microvascular complications and did not appear to affect myocardial infarction rates in a new cohort study that followed patients over four years. More...

Patients report emotional factors play big role in glucose self-monitoring, survey suggests

For patients with type 2 diabetes, emotional factors may influence glucose self-monitoring behavior as much or more than practical factors, a new study suggests. More...

Higher glucose levels associated with dementia even in non-diabetic patients

Higher glucose levels may be a risk factor for dementia among patients with and without diabetes, a study found. More...


Test yourself

MKSAP Quiz: Lower hemoglobin A1c after surgery

This month's quiz asks readers to evaluate a 56-year-old man with type 2 diabetes in a follow-up after repair of a bleeding duodenal ulcer. More...


From ACP InternistWeekly

Telmisartan and valsartan associated with fewer hospitalizations for cardiovascular events than other ARBs, study finds

In patients with diabetes, telmisartan and valsartan were associated with lower rates of hospitalization for cardiovascular events than other angiotensin-receptor blockers (ARBs), according to a recent retrospective study. More...


From ACP Journal Club

Meta-analysis: Atorvastatin reduces CV events and increases new-onset diabetes in patients with coronary disease

In a meta-analysis, patients with two to four risk factors for diabetes were more likely to have new-onset diabetes if they took higher doses of statins. More...


Tool of the month

What do I need to tell patients about hyperglycemia?

Patients with type 1 or 2 diabetes can benefit from advice about how to respond to episodes of hyperglycemia. More...


FDA update

Hemoglobin A1c test approved for diagnosis

The FDA recently approved the first hemoglobin A1c (HbA1c) test specifically labeled for diagnosing diabetes. More...


Keeping tabs

Spotlight on hypoglycemia

The risks and consequences of hypoglycemia were described by several studies published recently. More...


Physician editor: Daisy Smith, MD, FACP



Highlights


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Aggressive glucose control may not improve micro-, macrovascular outcomes in type 2 diabetes

Aggressive glucose control strategies yielded mixed results for microvascular complications and did not appear to affect myocardial infarction (MI) rates in a new cohort study that followed patients over four years.

Researchers studied adults with type 2 diabetes who had hemoglobin A1c (HbA1c) values less than 7% while taking two or more oral agents or basal insulin, followed by at least one HbA1c value of 7% to 8.5%. Patients were followed beginning on the date of the first HbA1c value of ≥7% until a clinical event, death, or disenrollment occurred or until the end of the study. The study defined glucose control strategies as first intensification of glucose-lowering therapy at HbA1c levels of ≥7%, ≥7.5%, ≥8%, or ≥8.5%. Study end points were acute MI, onset or progression of albuminuria, and progression or lack of progression to worse renal function based on estimated glomerular filtration rate (GFR). The study results were published online July 22 by Diabetes Care.

Of 58,671 patients, 1,655 (2.82%) had an acute MI during follow-up. Acute MI rates did not appear to differ according to treatment intensification strategy, although a trend was seen toward fewer acute MIs with treatment intensification at an HbA1c of ≥7% compared with ≥8.5% (P=0.08) and ≥8% compared with ≥8.5% (P=0.05). Of 57,927 patients in the kidney function analysis, 25,930 (44.76%) had a decrease in estimated GFR. Decreased renal function was significantly more common in patients who received treatment intensification at an HbA1c of ≥7% compared with ≥8% (P=0.04) or ≥8.5% (P=0.03), but not compared with ≥7.5% (P=0.18).

Of 51,179 patients in the albuminuria analysis, 12,085 (23.61%) had onset or progression of albuminuria. Albuminuria onset or progression was less likely in patients who received treatment intensification at an HbA1c of ≥7% (P=0.02), ≥7.5% (P=0.04), and ≥8% (P=0.01) compared with ≥8.5%, but no advantages were seen when comparing intensification at ≥7% with ≥7.5% (P=0.35), ≥7.5% with ≥8% (P=0.73), or ≥7% with ≥8% (P=0.27).

The authors noted that longer follow-up could have modified their results and that they were unable to model mortality as an outcome, among other limitations. However, they concluded that their results confirm those of larger trials, such as ACCORD and ADVANCE, in a broader range of patients. "In a large representative cohort of adults with type 2 diabetes, more aggressive glucose-control strategies have mixed short-term effects on microvascular complications and do not reduce the myocardial infarction rate over 4 years of follow-up," they wrote. They called for larger trials to confirm their results over longer periods.


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Patients report emotional factors play big role in glucose self-monitoring, survey suggests

For patients with type 2 diabetes, emotional factors may influence glucose self-monitoring behavior as much or more than practical factors, a new study suggests.

Researchers distributed an anonymous 68-item survey to attendees of a one-day conference for people with diabetes held in seven U.S. urban areas in 2009. Inclusion criteria included having type 2 diabetes for at least 12 months, being at least 18 years old, and being able to read and write in English. The survey aimed to collect data on actual and recommended self-monitoring of blood glucose frequency and perceived obstacles to self-monitoring. Principal component analysis was used to classify 12 obstacles into three types, and regression analyses were then used to examine associations between these three types and self-monitoring behavior. Results were published online July 19 by Diabetic Medicine.

Of the 886 patients included in the final analysis, 64.5% (n=571) were non-insulin users and 35.5% (n=315) were insulin users. Thirty-eight percent of insulin users and 45.9% of non-insulin users said their weekly self-monitoring frequency was less than what was recommended by clinicians. The mean frequency of self-monitoring was 19.2 (± 12.3) times per week for insulin users and 10.0 (± 8.7) for non-insulin users; reports of clinician recommendations averaged 22.2 (± 10.6) tests/week for insulin users and 13.7 (± 9.3) for non-insulin users. Insulin users were more likely than non-insulin users to share results with clinicians (P<0.01).

On analysis, the three main obstacles to self-monitoring were "avoidance" (not wanting to think about the results or about diabetes in general), "pointlessness" (feeling powerless about results) and "burden" (i.e., practical nuisances, such as finding the task too expensive or unpleasant). Higher burden scores weren't associated with any change in self-monitoring behaviors. Results didn't differ by insulin versus non-insulin use.

Avoidance (β= −0.12; P<0.01) and pointlessness (β= −0.15; P<0.001) were significant independent predictors of how often glucose self-monitoring data were shared with a clinician. They also predicted whether or not these data were used to make management adjustments (avoidance: odds ratio [OR], 0.74; P<0.001; pointlessness: OR, 0.75; P<0.01). The direction of these associations indicated high avoidance and pointlessness scores were associated with less self-monitoring and data sharing.

"Emotional obstacles to self-monitoring [avoidance and pointlessness] are more critical than day-to-day behavioral obstacles [burden]…," the authors wrote. Clinicians should address these obstacles directly with patients by not appearing to "blame" patients for high glucose values, and by taking time to review self-monitoring results so patients feel their effort is worthwhile, the authors said.

Study limitations include its generalizability, given that subjects were motivated to attend a one-day diabetes conference. Also, data were derived from patient self-reports, and the pool of obstacles was fairly small and may not have captured other aspects of self-monitoring about which patients have concerns, the authors wrote.


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Higher glucose levels associated with dementia even in non-diabetic patients

Higher glucose levels may be a risk factor for dementia among patients with and without diabetes, a study found.

To examine the relationship between glucose levels and dementia, researchers used 35,264 measurements of glucose levels and 10,208 measurements of glycated hemoglobin levels from 2,067 participants without dementia at a single health care system in the state of Washington, as part of the Adult Changes in Thought study.

In the study, 232 people with diabetes and 1,835 without it were randomly chosen, and their measurements were stratified by diabetes status, and then adjusted for age, sex, study cohort, educational level, level of exercise, blood pressure, coronary and cerebrovascular diseases, atrial fibrillation, smoking, and treatment for hypertension. Researchers assessed dementia every two years through the Cognitive Abilities Screening Instrument, which ranges from 0 to 100 (higher scores show better cognitive functioning). Results were published Aug. 8 in the New England Journal of Medicine.

Dementia developed in 524 participants (25.4%): 74 had diabetes (21.6% of all diabetics) and 450 (26.1% of non-diabetics) didn't. Among patients who didn't have diabetes, higher average glucose levels in the past five years were associated with an increased risk of dementia (P=0.01); for example, an average glucose level of 115 mg/dL was associated with a hazard ratio (HR) for dementia of 1.18 compared to 100 mg/dL (95% CI, 1.04 to 1.33). Among diabetics, higher average glucose levels were also related to higher risk of dementia: HR 1.40 for average glucose of 190 mg/dL compared to 160 mg/dL (95% CI, 1.12 to 1.76; P=0.002).

Researchers noted that their research implies that any incremental increase in glucose levels may be associated with an increased risk of dementia. They wrote, "These data suggest that higher levels of glucose may have deleterious effects on the aging brain. Our findings underscore the potential consequences of temporal trends in obesity and diabetes and suggest the need for interventions that reduce glucose levels."



Test yourself


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MKSAP Quiz: Lower hemoglobin A1c after surgery

A 56-year-old man comes to the office for a follow-up evaluation. Three weeks ago, the patient had surgery to repair a bleeding duodenal ulcer. During his 7-day hospitalization, he was given six units of packed red blood cells. He was discharged 2 weeks ago with instructions to take omeprazole. The patient has a 12-year history of type 2 diabetes mellitus, and his hemoglobin A1c values have ranged from 8.5% to 9.0% for the past 5 years. Since hospital discharge, his blood glucose levels have ranged from 140 to 160 mg/dL (7.8-8.9 mmol/L). He has a 40-pack-year smoking history but has not smoked since the surgery. Although work was increasingly stressful before ulcer repair, he says he has been feeling more relaxed since discharge and has been eating healthier foods. Medications are metformin, glyburide, simvastatin, and omeprazole.

mksap.gif

On physical examination, temperature is 36.9 °C (98.4 °F), blood pressure is 142/83 mm Hg, pulse rate is 82/min, and respiration rate is 14/min; BMI is 34. Other physical examination findings are unremarkable.

Results of laboratory studies show a hematocrit of 43% and a hemoglobin A1c value of 6.2% (estimated average plasma glucose level, 130 mg/dL [7.2 mmol/L]).

Which of the following best explains the reduction in his hemoglobin A1c value?

A. Blood transfusions
B. Healthier diet
C. Omeprazole interference with the hemoglobin A1c assay
D. Smoking cessation

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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Telmisartan and valsartan associated with fewer hospitalizations for cardiovascular events than other ARBs, study finds

In patients with diabetes, telmisartan and valsartan were associated with lower rates of hospitalization for cardiovascular events than other angiotensin-receptor blockers (ARBs), according to a recent retrospective study.

The population-based cohort study included about 54,000 Ontario residents over age 65 who had type 2 diabetes and started treatment with telmisartan, valsartan, candesartan, irbesartan or losartan between 2001 and 2011. The primary outcome was a composite of hospital admission for acute myocardial infarction, stroke or heart failure. Results were published by CMAJ on July 8.

After multivariable adjustment, patients taking telmisartan or valsartan had a lower risk of the primary outcome than those on irbesartan (adjusted hazard ratio [HR] for telmisartan, 0.85 [95% CI, 0.74 to 0.97]; HR for valsartan, 0.86 [95% CI, 0.77 to 0.95]). There were no significant differences in the primary outcome among the other ARBs. The researchers also found a reduction specifically in hospitalizations for heart failure with telmisartan compared to irbesartan (HR, 0.79 [95% CI, 0.66 to 0.96]).

The observed advantages of telmisartan may be due to its activation of the PPARγ receptor, the study authors speculated. The benefit found for valsartan is harder to explain and was attenuated by adjustment for dose, but it may be related to inhibition of platelet aggregation, they wrote. The study was limited by its observational nature, but many variables were controlled for and a randomized trial of all these agents is unlikely, so the authors concluded telmisartan and valsartan may be the preferred ARBs for older patients with diabetes. The results are not necessarily applicable to younger patients or those without diabetes, they noted.

An accompanying editorial expressed doubts about the authors' conclusions, arguing that PPARγ agonism would not lead to the cardiovascular benefit seen in the study and that there was no likely explanation for the observed advantage of valsartan. The results are intriguing, the editorialist wrote, but "there is scant evidence to support preferring one drug in this class over another for patients with type 2 diabetes."



From ACP Journal Club


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Meta-analysis: Atorvastatin reduces CV events and increases new-onset diabetes in patients with coronary disease

In a meta-analysis including 15,000 patients from two randomized controlled trials (taking 80 mg/day of atorvastatin, 10 mg/day of atorvastatin, or 20 to 40 mg/day of simvastatin), those with two to four risk factors for diabetes were more likely to have new-onset diabetes (NOD) in the high-dose statin group. Patients with no or one risk factor had no increase in NOD. However, the number of cardiovascular (CV) events was significantly lowered by the higher dose in both risk-factor groups.

The study was published in the January 15 Journal of the American College of Cardiology. The following commentary by Sanjum S. Sethi, MD, and Michael E. Farkouh, MD, MSc, was published in the ACP Journal Club section of the July 16 Annals of Internal Medicine.

Statins are a mainstay of therapy for patients with established CAD [coronary artery disease], but recent reports suggest that high doses may increase risk for NOD. Waters and colleagues address this issue in a meta-analysis of 2 pivotal trials. Overall, the number needed to harm for NOD is comparable to the number needed to treat to prevent 1 additional CV event. Analysis by the number of baseline risk factors for diabetes showed that the risk for NOD was greater in patients with 2 to 4 risk factors.

The mechanism by which NOD is related to statin use is unknown but may be linked to increased muscle insulin resistance secondary to statin-induced myopathy. Risk factors for NOD in patients treated with statins are not dissimilar to those in patients who are not—statins may simply hasten the onset of diabetes in patients already at high risk.

The increased risk for microvascular complications from NOD should be weighed against the benefit of reducing CAD risk with statins in each patient with dysglycemia. For younger patients with CAD, NOD may have important implications since diabetic complications increase with time, whereas the preventive effects of statins may be more stable. We recommend that patients at risk for diabetes be informed about the risk for NOD and its complications. It is reasonable to treat those at highest risk with moderate-dose statins to mitigate some of the risk for NOD while other interventions are being pursued. Overall, this doesn't change the playing field for most patients with CAD since all patients, regardless of the number of risk factors for NOD, had a reduction in major CV events.



Tool of the month


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What do I need to tell patients about hyperglycemia?

Patients with type 1 or 2 diabetes can benefit from advice about how to respond to episodes of hyperglycemia.

  • Patients should be encouraged to drink sugar-free liquids when hyperglycemic to prevent dehydration and help lower blood glucose levels.
  • If your patient has a high blood glucose reading that is unexpected/unexplained, recommend rechecking the blood glucose after handwashing to make sure no residual sugary substances have led to a spurious reading.
  • Encourage your patients to try to determine what causes episodes of hyperglycemia: Did they eat more carbohydrates then normal? Have they been less active? Did they forget their medicine? Is their insulin old (and potentially less potent)?
  • Finally, encourage patients to keep track of their high blood glucose levels and bring the records to their appointments.


FDA update


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Hemoglobin A1c test approved for diagnosis

The FDA recently approved the first hemoglobin A1c (HbA1c) test specifically labeled for diagnosing diabetes (COBAS INTEGRA 800 Tina-quant HbA1cDx assay). Many clinicians have already been using HbA1c tests to diagnose diabetes, but they were not specifically designed or approved for this use, making it difficult to know which tests were sufficiently accurate. In support of marketing clearance for the new assay, investigators analyzed 141 blood samples and found less than 6% difference in the accuracy of test results from the new test compared to the standard reference for hemoglobin analysis.



Keeping tabs


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Spotlight on hypoglycemia

The risks and consequences of hypoglycemia were described by several studies published recently.

First, a meta-analysis, published by BMJ on July 30, found that type 2 diabetes patients who had episodes of severe hypoglycemia were much more likely to have cardiovascular disease (relative risk 2.05, 95% CI, 1.74 to 2.42; P<0.001). The authors, who analyzed six studies with more than 900,000 patients, calculated that the excess fraction of cardiovascular disease incidence attributable to severe hypoglycemia was 1.56% (95% CI, 1.32% to 1.81%; P<0.001). The result was significant enough after adjustment that it is unlikely to be explained by comorbid severe illness, the authors concluded, recommending solutions such as individualized therapy targets, agents unlikely to cause hypoglycemia (like metformin), and patient self-monitoring.

In a prospective, population-based study of 783 older adults with diabetes, hypoglycemic events were found to be associated with a doubling of risk of developing dementia. According to results published by in the July 22 JAMA Internal Medicine (and online-first June 10), 7.8% of the study population (or 61 patients) had a hypoglycemic event requiring hospitalization, and 34.4% of that group developed dementia, compared to 17.6% of non-hypoglycemic patients (hazard ratio [HR], 2.1; 95% CI, 1.0 to 4.4, P<0.001). Patients who developed dementia also had higher risk of subsequent hypoglycemia (14.2% vs. 6.3%, P<0.001; HR, 3.1; 95% CI, 1.5-6.6). The results provide evidence of a reciprocal association between hypoglycemia and dementia, and should encourage clinicians to consider cognitive function in the clinical management of older patients with diabetes, the study authors concluded.

Finally, a survey of type 2 diabetes patients in a large health care system found that severe hypoglycemia is common, regardless of patients' hemoglobin A1c (HbA1c) levels. Of the 9,094 Californian survey respondents (mean age 59.5), 10.8% reported experiencing severe hypoglycemia in the previous year. Patients with the lowest and highest HbA1cs reported more hypoglycemia than those in the middle, according to results published online by Diabetes Care July 30. With an HbA1c of 7–7.9% as the reference, the adjusted relative risk of hypoglycemia was 1.25 (95% CI 0.99–1.57) for patients with HbA1c <6%, 1.01 (0.87–1.18) for 6–6.9%, 0.99 (0.82–1.20) for 8–8.9%, and 1.16 (0.97–1.38) for ≥9%. Age, diabetes duration, and category of diabetes medication did not significantly modify the association. The study's finding that self-reported severe hypoglycemia occurs just as frequently among patients with poor glycemic control as those with near-normal glycemia counters conventional wisdom, the researchers noted. It may highlight the risks of intensifying therapy in patients who have not already responded well, and shows that concerns about hypoglycemia should not be limited to patients with low HbA1cs.


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MKSAP Answer and Critique



The correct answer is A. Blood transfusions. This item is available to MKSAP 16 subscribers as item 37 in the Endocrinology section. Information about MKSAP 16 is available online.

The six units of packed red blood cells that this patient received while hospitalized most likely are responsible for his low hemoglobin A1c value. In patients receiving hemodialysis, those with hemolytic anemia or certain hemoglobinopathies, or those with recent blood transfusions, hemoglobin A1c values may be falsely lowered because of the presence of erythrocytes less than 120 days old in the sample. In this patient, not enough time has elapsed since the blood was transfused for the erythrocytes to become glycosylated and reflect a true hemoglobin A1c level.

Although eating a healthier diet might lower his blood glucose levels over the next few months, not enough time has passed for this lifestyle intervention to affect his hemoglobin A1c value so profoundly. His blood glucose log shows premeal values of 140 to 160 mg/dL (7.8-8.9 mmol/L), which means that postprandial values are likely to be even higher and not compatible with a hemoglobin A1c value of 6.2%.

Omeprazole does not interfere with hemoglobin A1c assays and thus is not responsible for his dramatically lower value.

Cessation of cigarette smoking, although an inherently positive lifestyle change, will not affect the hemoglobin A1c level.

Key Point

  • Hemoglobin A1c values may be falsely lowered in patients who have received recent blood transfusions.

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Test yourself

A 42-year-old woman is evaluated for an 8-month history of crampy abdominal pain and three loose bowel movements per day. The pain is relieved by a bowel movement. There are no nocturnal bowel movements, and there is no blood or dark tarry material in the stool. She has not had fever, night sweats, or weight loss. She has a history of Hashimoto disease and is treated with levothyroxine. Following a physical exam, rectal exam, and lab tests, what is the most appropriate next step in management?

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