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

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ACP DiabetesMonthly



In the News for the month of January 2013




Highlights

Retinopathy may predict nephropathy, be predicted by nonhealing ulcers

The presence of diabetic retinopathy was associated with the risk of other complications, two recent studies concluded. More...

Clinicians' communication skills may affect medication refill adherence

Patients with diabetes who rated their clinicians as poor communicators were less likely to refill cardiometabolic medications in a timely manner, a study found. More...

Intensive lifestyle intervention associated with partial remission of type 2 diabetes

An intensive lifestyle intervention was associated with partial remission of type 2 diabetes when compared with diabetes support and education, according to a new study. More...


Test yourself

MKSAP Quiz: New-onset heart failure after medication adjustments

This month's quiz asks readers to evaluate a 71-year-old man with type 2 diabetes and new dyspnea on exertion. More...


From ACP InternistWeekly

ADA recommendations increase blood pressure target to below 140 mm Hg systolic in diabetic patients

A higher maximum systolic blood pressure target for diabetics is one of the most significant changes in the American Diabetes Association's 2013 Standards of Medical Care. More...

Diabetes risk from statins may be offset by reduction in cardiovascular events

Atorvastatin, 80 mg/d, carries a higher risk of developing diabetes than do lower doses, but only among patients who already have multiple risk factors, a study found. More...


Tool of the month

Recommending eye examinations

All adults with diabetes should undergo an initial comprehensive, dilated eye examination by an ophthalmologist knowledgeable and experienced in diagnosing retinopathy and its management. More...


Keeping tabs

Spotlight on screening

New data on who to screen for diabetes and how to screen them were offered by a few studies published in the past month. More...


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



Highlights


.
Retinopathy may predict nephropathy, be predicted by nonhealing ulcers

The presence of diabetic retinopathy was associated with the risk of other complications, two recent studies concluded.

The first study, a meta-analysis of 26 papers involving 2,012 patients, concluded that proliferative diabetic retinopathy may be a highly specific indicator for diabetic nephropathy.

The paper, which was published online in Diabetologia on Dec. 12, found that pooled sensitivity of diabetic retinopathy to predict diabetic nephropathy was 0.65 (95% CI, 0.62 to 0.68) and the specificity was 0.75 (95% CI, 0.73 to 0.78). The pooled positive predictive value of diabetic retinopathy to predict diabetic nephropathy was 0.72 (95% CI, 0.68 to 0.75) and the negative predictive value was 0.69 (95% CI, 0.67 to 0.72).

The area under the summary receiver-operating characteristic curve was 0.75, and the diagnostic odds ratio was 5.67 (95% CI, 3.45 to 9.34). For proliferative diabetic retinopathy, the pooled sensitivity was 0.25 (95% CI, 0.16 to 0.35), while the specificity was 0.98 (95% CI, 0.92 to 1.00).

Researchers wrote that while kidney biopsy is the gold standard method for identifying diabetic nephropathy, it cannot be done in all cases and requires 24 hours of observation to watch for complications. "In contrast, assessment of DR [diabetic retinopathy] is very convenient and is routinely performed as part of a physical examination in outpatient departments," the authors wrote. "Although the overall test performance was not as high as expected, measuring DR may be considered useful for predicting DN [diabetic nephropathy] in the light of its simplicity and non-invasiveness."

A second study considered whether non-ophthalmic consequences of diabetes (including nephropathy but also elevated hemoglobin A1c [HbA1c] levels and nonhealing ulcers) could predict the progression of diabetic retinopathy from nonproliferative to proliferative. Researchers conducted a retrospective cohort analysis using a claims database of all eye care recipients 30 years or older enrolled in a large managed care network from 2001 to 2009. Results appeared Jan. 3 in Diabetes Care.

Among the 4,617 enrollees with newly diagnosed nonproliferative diabetic retinopathy, 307 (6.6%) progressed to proliferative cases. Every 1-point increase in HbA1c was associated with a 14% increase in risk of developing progressive retinopathy (adjusted hazard ratio, 1.14; 95% CI, 1.07 to 1.21). Those with nonhealing ulcers had a 54% increased risk of progressing to proliferative retinopathy (hazard ratio, 1.54; 95% CI, 1.15 to 2.07) compared to those without. Those with nephropathy had a 29% increased risk of progression compared to those without, but the statistical significance of this finding was marginal (hazard ratio, 1.29; 95% CI, 0.99 to 1.67).

The 5-year probability of progression for those with nonproliferative diabetic retinopathy was 5% (range, 2% to 8%) for those who had few risk factors, but 38% (range, 14% to 55%) for those with multiple risk factors.

"If confirmed, the association between nonhealing ulcers and retinopathy progression could have important implications for clinical practice," the authors wrote. "Control of nonhealing ulcers may help to reduce progression of NPDR [nonproliferative diabetic retinopathy] to PDR [proliferative diabetic retinopathy], the risk of vision loss, and the need for laser surgery."


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Clinicians' communication skills may affect medication refill adherence

Patients with diabetes who rated their clinicians as poor communicators were less likely to refill cardiometabolic medications in a timely manner, a study found.

Researchers performed a cross-sectional analysis of 9,377 patients from the Diabetes Study of Northern California, which comprised randomly sampled respondents from a Kaiser Permanente survey. Patients took one or more oral hypoglycemic, lipid-lowering or antihypertensive medication in the 12 months before the survey. Researchers had patients measure the communication of their clinicians via four items on the Consumer Assessment of Healthcare Providers and Systems Survey (CAHPS) score and four items from the Trust in Physicians and Interpersonal Processes of Care instruments. They used pharmacy data to help determine adherence, which was measured via a "continuous medication gap" (CMG). The CMG is the proportion of days without enough medication across different refill intervals. Poor adherence was defined as more than a 20% CMG.

Thirty percent of the patients in the analysis had poor refill adherence for their medication(s). For each 10-point decline in CAHPS score, adjusted prevalence of poor adherence went up by 0.9% (P=0.01). Patients were more likely to have poor adherence if they gave their clinicians lower ratings for involving patients in decisions (4% adjusted difference in ratings; P=0.04), understanding patients' problems with treatment (5% adjusted difference; P=0.02) and eliciting confidence and trust (6% adjusted difference; P=0.03) than if they gave higher ratings. The association between adherence and communication was stronger for hypoglycemic medications than other medications. Results were published online Dec. 31 by Archives of Internal Medicine.

The results suggest patient communication ratings are "modestly predictive" of inadequate adherence to medication refills, the authors wrote, though it is unclear whether clinician communication can be modified or if doing so would improve adherence. Targeting clinicians with poorer communication ratings, or focusing on specific skills related to shared decision making, may be helpful, they added.

Editorialists noted that the study had several "methodological strengths that further its relevance and importance," including use of objective pharmacy data, a large and diverse study population, and sophisticated analytical methods. The study is "an important stop on the road to patient centeredness," they noted, adding that it is also important for patients to take responsibility for their health.


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Intensive lifestyle intervention associated with partial remission of type 2 diabetes

An intensive lifestyle intervention was associated with partial remission of type 2 diabetes when compared with diabetes support and education, according to a new study.

Researchers performed an ancillary observational analysis using data from the Look AHEAD (Action for Health for Diabetes) study, a four-year randomized, controlled trial sponsored by the National Institutes of Health that compared an intensive lifestyle intervention with diabetes support and education in overweight U.S. adults with type 2 diabetes. The Look AHEAD study was designed to examine whether weight loss decreased incidence of cardiovascular disease but was stopped early, in October 2012, when no such decrease was seen in the intervention versus the control group. The main outcome measure in the current study was partial or complete diabetes remission, which was defined as transition to a prediabetes or nondiabetic glycemia level after meeting diabetes criteria. The study results were published in the Dec. 19 Journal of the American Medical Association.

A total of 4,503 adults from the Look AHEAD sample were included in this analysis. The mean age was 59 years, and the mean body mass index at baseline was 35.8 kg/m2. Median time since diabetes diagnosis was five years. Those randomly assigned to the intensive intervention (n=2,241) received weekly group and individual counseling for the first six months of the trial, then three sessions per month for the next six months along with twice-monthly contact and regular refreshers in the next two to four years. Those assigned to the control group (n=2,262) were offered three group sessions per year addressing diet, physical activity and social support.

Patients in the intensive lifestyle group had lost significantly more weight at year 1 and year 4 compared with the control group (net differences, −7.9% and −3.9%; P<0.001) and also had a significantly greater increase in fitness (net differences, 15.4% and 6.4%; P<0.001). Partial or complete diabetes remission was significantly more common in the intervention group than in the control group at year 1 and year 4 (prevalence, 11.5% vs. 2.0% and 7.3% vs. 2.0%, respectively; P<0.001 for each comparison). Rates of continuous, sustained remission for at least two, at least three, and four years were 9.2% (95% CI, 7.9% to 10.4%), 6.4% (95% CI, 5.3% to 7.4%), and 3.5% (95% CI, 2.7% to 4.3%) in the intervention group and 1.7% (95% CI, 1.2% to 2.3%), 1.3% (95% CI, 0.8% to 1.7%), and 0.5% (95% CI, 0.2% to 0.8%) in the control group.

The authors said that their analyses should be considered exploratory since the Look AHEAD study did not include diabetes remission as one of its primary objectives. In addition, they noted that they did not examine the mechanism by which the intervention may have affected glycemic levels. Despite these and other limitations, they concluded that their findings indicate a potential association between an intensive lifestyle intervention and partial diabetes remission in some patients with type 2 disease.

The authors of an accompanying editorial agreed that such intervention could have benefit, especially in patients with early diabetes, but noted that major cardiovascular events and death do not appear to be affected. "Perhaps future analyses…will identify subgroups of patients with type 2 diabetes that may warrant intensive lifestyle or medical intervention to reduce cardiovascular risk," they wrote. "However, a more potent intervention—bariatric surgery—already appears to achieve what intensive medical and lifestyle intervention cannot: reducing cardiovascular events and mortality rates among severely obese patients with type 2 diabetes."



Test yourself


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MKSAP Quiz: New-onset heart failure after medication adjustments

A 71-year-old man is evaluated in the emergency department for new dyspnea on exertion. He has a 15-year history of type 2 diabetes mellitus and has had a number of changes in his medications over the past 12 weeks to improve glycemic control. His dosage of metformin has been increased to 1000 mg/d, glyburide to 10 mg/d, and pioglitazone to 45 mg/d. Within the past week, bedtime insulin glargine was initiated.

mksap.jpg

On physical examination, blood pressure is 140/90 mm Hg, pulse rate is 90/min, and respiration rate is 20/min. Jugular venous distention, an S3, basilar pulmonary crackles, and 3+ pitting edema at the ankles are noted.

Besides the initiation of insulin glargine, which of the following most likely contributed to these findings?

A. Increased glyburide dosage
B. Increased metformin dosage
C. Increased pioglitazone dosage
D. Medication-associated hypoglycemia

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


.

From ACP InternistWeekly


.
ADA recommendations increase blood pressure target to below 140 mm Hg systolic in diabetic patients

A higher maximum systolic blood pressure target for diabetics is one of the most significant changes in the American Diabetes Association's 2013 Standards of Medical Care.

The standards, which are revised annually, are based on the most current scientific evidence and provide guidance on treating children and adults with all types of diabetes. They were published online Dec. 20, 2012, and in a special supplement to the January 2013 Diabetes Care.

Several changes were made to the recommendations for 2013, the most significant being an increase in the systolic blood pressure goal for many people with diabetes from less than 130 mm Hg to less than 140 mm Hg. The revision was based on several new meta-analyses showing little additional benefit from lower targets, according to a press release. However, lower targets may still be appropriate for some patients, for example those who are younger or have a higher risk of stroke, the recommendations noted.

Another recommendation change affects hospitalized patients who have not been previously diagnosed with diabetes. If such patients have risk factors for diabetes and exhibit hyperglycemia during hospitalization, physicians should consider obtaining a hemoglobin A1c test, the standards now say. The standards have also been updated to reflect new recommendations from the Centers for Disease Control and Prevention on hepatitis B vaccination. Diabetic patients age 19 to 59 should be vaccinated, and vaccination should be considered for those 60 and over.

Recommendations on self-monitoring of blood glucose for patients who take multiple doses of insulin per day have also changed. Previously, the recommendations called for self-monitoring three or more times a day. The 2013 standards specify that these patients should test their blood glucose prior to meals and snacks, occasionally after eating, at bedtime, before exercise, when hypoglycemia is suspected or has occurred and prior to critical tasks such as driving.

The new recommendations also contain changes regarding diabetes self-management education, screening and treatment of cardiovascular risk factors in prediabetes, and emphasizing statin therapy over specific low-density lipoprotein cholesterol goals. A summary of the revisions and an executive summary of the standards are online.


.
Diabetes risk from statins may be offset by reduction in cardiovascular events

Atorvastatin, 80 mg/d, carries a higher risk of developing diabetes than do lower doses, but only among patients who already have multiple risk factors, a study found.

Researchers examined data from more than 15,000 patients with coronary disease but without diabetes at baseline in two trials, TNT (Treating to New Targets) and IDEAL (Incremental Decrease in Endpoints Through Aggressive Lipid Lowering). They considered four risk factors that independently predicted new-onset diabetes, including fasting blood glucose above 100 mg/dL, fasting triglycerides above 150 mg/dL, body mass index above 30 kg/m2, and history of hypertension. Results appeared in the January Journal of the American College of Cardiology.

Among 8,825 patients with no or one diabetes risk factor at baseline, new-onset diabetes developed in 142 patients in the 80-mg atorvastatin group compared with 148 of those taking 10 mg of atorvastatin or 20 to 40 mg of simvastatin (3.22% vs. 3.35%; hazard ratio [HR], 0.97; 95% CI, 0.77 to 1.22).

Of the 6,231 patients with two to four risk factors, new-onset diabetes developed in 448 of 3,128 in the 80-mg atorvastatin group and in 368 of 3,103 in the lower-dose groups (14.3% vs. 11.9%; HR, 1.24; 95% CI, 1.08 to 1.42; P=0.0027). Researchers noted that cardiovascular events were significantly reduced with 80 mg of atorvastatin in both low- and high-risk groups.

"These results should reassure physicians treating patients at low risk for diabetes," the authors wrote. "Such patients do not appear to incur an increased risk of diabetes with high-dose atorvastatin and derive benefit in terms of CV [cardiovascular] event reduction. Among the 6,231 patients in the TNT and IDEAL trials at high risk for NOD [new-onset diabetes], treatment with atorvastatin 80 mg compared with a lower statin dose was associated with 80 more cases of NOD and the prevention of 94 major CV events in 58 patients."

Furthermore, the impact of new-onset diabetes is relatively minor compared to the cardiovascular events included in the study, such as death, myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke, the authors said.

The authors continued, "In considering the balance between NOD and CV event prevention, it is worth noting that the microvascular and macrovascular complications of diabetes occur relatively uncommonly during the first decade after diagnosis. Many patients with established vascular disease, such as those in this study, will die from an atherosclerotic event before they develop complications from diabetes."



Tool of the month


.
Recommending eye examinations

All adults with diabetes should undergo an initial comprehensive, dilated eye examination by an ophthalmologist knowledgeable and experienced in diagnosing retinopathy and its management.

  • Type 1 diabetes: Initial eye examination should occur within 5 years after the onset of diabetes.
  • Type 2 diabetes: Initial eye examination should occur shortly after diagnosis.

All patients with diabetes should receive annual follow-up eye examinations by an ophthalmologist.

  • More frequent evaluation is indicated if retinopathy is progressive.
  • Less frequent evaluations (every 2 to 3 years) may be considered on the advice of any eye care professional following one or more normal eye exams.

Women with diabetes who are planning a pregnancy should receive a comprehensive eye examination and should be counseled on the risk of the development or progression of retinopathy. For women with diabetes who are pregnant, a comprehensive eye examination is indicated during the first trimester.

From the ACP Diabetes Care Guide.



Keeping tabs


.
Spotlight on screening

New data on who to screen for diabetes and how to screen them were offered by a few studies published in the past month.

Women who have survived breast cancer appear to have an elevated risk of developing diabetes, according to a study in the December 2012 Diabetologia. Researchers compared the incidence of diabetes among more than 25,000 Canadian women 55 and over who were treated for breast cancer between 1996 and 2008 and more than 120,000 age-matched controls. Breast cancer patients had a slight increase in diabetes starting two years after diagnosis, which grew to a 20% higher risk by 10 years, leading study authors to conclude that "greater diabetes screening and prevention strategies among breast cancer survivors may be warranted."

Physicians may also want to keep a closer eye on women who undergo menopause at a relatively young age. A different study, which compared more than 3,000 postmenopausal women with type 2 diabetes to more than 4,000 controls, found that women who went through menopause before age 40 were 32% more likely to develop diabetes than those who had it at ages 50 to 54. A trend toward higher risk was also seen in women who experienced menopause between ages 40 and 44. A shorter reproductive life span was also associated with higher diabetes risk, according to the study, which was published online by Diabetes Care on Dec. 10.

Adult-onset autoimmune diabetes is more likely in patients who are leaner, female and younger according to a recent European study, published Dec. 17 by Diabetes Care. More than 6,000 relatively newly diagnosed (within five years) diabetic patients were tested for GAD antibodies (GADA) and antibodies to insulinoma-associated antigen-2 and zinc-transporter 8. Almost 9% of the patients were found to have GADA and another 0.9% had one of the other types. Patients with the antibodies tended to be younger, leaner and female, but researchers concluded that these patients are generally clinically indistinguishable from patients with type 2 diabetes at diagnosis and can only be certainly identified by antibody screening.

What is the best method to measure a waist circumference? Researchers measured the waists of almost 2,000 Taiwanese subjects two ways: at the superior border of the iliac crest (as recommended by the National Cholesterol Education Program Third Adult Treatment Panel) and midway between the lowest ribs and the iliac crest (as recommended by World Health Organization and International Diabetes Federation). The latter measure was more strongly correlated with visceral fat area especially in women and more strongly correlated with blood pressure, cholesterol, plasma glucose and C-reactive protein. The study authors conclude that the midway technique is a better method to identify central obesity, particularly in women. Their results were published online by Diabetes Care on Dec. 28.


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MKSAP Answer and Critique



The correct answer is C. Increased pioglitazone dosage. This item is available to MKSAP 15 subscribers as item 43 in the Endocrinology section. Part A of MKSAP 16 was released on July 31. More information is available online.

This patient's recently increased pioglitazone dosage most likely contributed to his diagnosis of heart failure. Edema, a recognized adverse effect of thiazolidinedione (TZD) therapy, occurs in 5% to 10% of all treated patients and in up to 20% of patients treated concurrently with insulin. Exacerbation of preexisting heart failure can result. However, there is no evidence of any direct negative effect of TZDs on cardiac function. The pathogenesis of fluid retention and potential heart failure with TZD therapy relates to this drug class's tendency to increase renal sodium retention, which typically resolves with discontinuation of the TZD. The U.S. Food and Drug Administration states that pioglitazone and rosiglitazone are contraindicated in patients with advanced heart failure (New York Heart Association class III or IV) and are not recommended in any patient with symptomatic heart failure (class II).

Sulfonylurea drugs, such as glyburide, can cause weight gain (not due to fluid retention) and hypoglycemia. These medications are metabolized by the liver and cleared by the kidneys and therefore should be used cautiously in patients with impaired hepatic or renal function. Sulfonylureas, however, do not cause heart failure, and the increased glyburide dosage is not responsible for this patient's dyspnea.

Metformin is currently contraindicated only in patients with decompensated heart failure, especially when renal function is abnormal or threatened. Metformin therapy, however, is not associated with a direct negative inotropic effect, and the increased dosage is an unlikely cause of this patient's symptoms.

There is no history of recent hypoglycemia. Also, hypoglycemia would not be expected to lead to heart failure.

Key Point

  • Thiazolidinedione use is not recommended in patients with New York Heart Association (NYHA) class II heart failure and is contraindicated in those with NYHA class III and IV heart failure.

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