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

Advertisement

ACP DiabetesMonthly



In the News for the month of February 2013




Highlights

Variable systolic blood pressure could be associated with nephropathy risk

Variations in systolic blood pressure could be associated with increased risk for diabetic nephropathy, according to a recent study. More...

Nearly 17% of newly diagnosed type 2 diabetes patients have silent MI

About one in six patients with newly diagnosed type 2 diabetes had evidence of a silent myocardial infarction, a new study found. More...

New pediatric guidelines for type 2 diabetes emphasize starting drugs, lifestyle changes simultaneously

Guidelines for treating type 2 diabetes in children and teenagers suggest integrating diet and exercise with medication, as well as offering advice on frequency of hemoglobin A1c and fingerstick blood glucose monitoring. More...


Test yourself

MKSAP Quiz: Photocoagulation therapy

This month's quiz asks readers to evaluate a 62-year-old man before he has panretinal laser photocoagulation therapy in both eyes. 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...


From ACP Journal Club

Hypoglycemia was associated with increased mortality in ICU patients regardless of glucose control strategy

A post hoc analysis of the NICE-SUGAR trial that included about 6,000 ICU patients compared intensive glucose control (targeting blood glucose levels of 81 to 108 mg/dL) and conventional glucose control (targeting levels ≤180 mg/dL). More...

A single screening for type 2 diabetes in high-risk adults did not reduce mortality over 10 years

A trial in the United Kingdom randomized 33 primary care practices and 20,000 of their high-risk patients to screening for diabetes or usual care. More...

Review: Intensive blood pressure control reduces stroke, but not mortality or MI, in type 2 diabetes

A meta-analysis compared five studies (including the ACCORD trial) that treated adults with type 2 diabetes with antihypertensive therapies to achieve prespecified blood pressure targets. More...


Tool of the month

Tips to help patients get the most from their insulin

The following information should be shared with patients to optimize their insulin therapy. More...


Keeping tabs

Spotlight on insulin timing

The timing of insulin injections for patients with type 2 diabetes was the focus of several studies published in the past month. More...


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



Highlights


.
Variable systolic blood pressure could be associated with nephropathy risk

Variations in systolic blood pressure could be associated with increased risk for diabetic nephropathy, according to a recent study.

Researchers in Kyoto, Japan, performed a retrospective cohort study of patients with type 2 diabetes who were treated as outpatients at a university clinic from April 2008 to September 2012. Systolic blood pressure was measured at each visit over one year, and coefficients of variation were calculated. The researchers then assessed changes in urinary albumin excretion or development of albuminuria over time and used multiple regression analysis and multiple Cox regression modeling to determine potential relationships between variability of systolic blood pressure and diabetic nephropathy. The study results were published online Jan. 22 by Diabetes Care.

A total of 354 consecutive patients with a mean age of 65.5 years were included in the study. The mean coefficient of variation of systolic blood pressure was 8.0% ± 4.0%, and average follow-up time was 3.76 ± 0.71 years. Blood pressure was measured an average of 7.19 times per patient during the initial study year. Two hundred eighteen patients had normoalbuminuria at baseline, and 28 patients developed albuminuria during the study period. In multiple regression analysis, an independent association was seen between the coefficient of variation of systolic blood pressure and change in urinary albumin excretion (β=0.1758; P=0.0108). In adjusted Cox regression analyses, average systolic blood pressure, coefficient of variation of systolic blood pressure, total cholesterol, and logarithm of triglycerides were each associated with an increased risk for albuminuria (hazard ratios, 1.047, 1.143, 1.024 and 18.40, respectively).

The authors acknowledged that all of the study patients were Japanese and that their results may not be generalizable to other settings. They also noted that variation in blood pressure may have been due to medications and that the study was small, among other limitations. However, they concluded that visit-to-visit variability in systolic blood pressure could indicate risk for nephropathy progression or albuminuria in patients with type 2 diabetes, and that the role of this variability should be clarified.


.
Nearly 17% of newly diagnosed type 2 diabetes patients have silent MI

About one in six patients with newly diagnosed type 2 diabetes had evidence of a silent myocardial infarction (SMI), a new study found.

U.K. researchers examined data from the 5,102 patients who were in the U.K. Prospective Diabetes Study and used regression analysis to determine the effect of SMI on the outcomes of death or subsequent fatal or nonfatal MI. SMI was defined as the presence of pathological Q-waves without typical cardiac symptoms and was detected by electrocardiogram (ECG) screening. Results were published online Jan. 29 by Circulation.

Nearly 2,000 study patients (n=1,967) had complete baseline data. Of these, 16.6% (n=326) had ECG evidence of SMI at enrollment; these patients were more likely to be older, female and sedentary than those without SMI. They were also more likely to be taking aspirin and lipid-lowering therapy, had a greater prevalence of microangiopathy, and had a higher mean blood pressure even with more intensive antihypertensive treatment.

SMI was associated with a 49% increased rate of subsequent fatal MI and a 26% increased rate of all-cause mortality, a significant difference after adjustment for conventional cardiovascular risk factors. SMI at diagnosis of type 2 diabetes, however, was not associated with a first non-fatal MI. Though SMI at diagnosis was more common in females, the SMI-associated increase in risk of subsequent fatal MI was independent of sex. Adding SMI to the factors in the original study's cardiovascular "risk engine" (which included age at diagnosis, ethnicity, gender, smoking, hemoglobin A1c level, systolic blood pressure and total HDL cholesterol ratio) only marginally improved the engine's ability to predict key cardiovascular outcomes.

Based on the study results, clinicians who find evidence of SMI on routine ECG screening of patients with type 2 diabetes should carefully review the adequacy of management of modifiable cardiovascular risk factors, the study authors concluded.


.
New pediatric guidelines for type 2 diabetes emphasize starting drugs, lifestyle changes simultaneously

Guidelines for treating type 2 diabetes in children and teenagers suggest integrating diet and exercise with medication, as well as offering advice on frequency of hemoglobin A1c (HbA1c) and fingerstick blood glucose monitoring.

The guidelines appeared in the February Pediatrics.

Clinicians should prescribe a lifestyle modification program, including nutrition and physical activity, and can also start metformin as first-line therapy. They can incorporate the Academy of Nutrition and Dietetics' Pediatric Weight Management Evidence-Based Nutrition Practice Guidelines in their dietary or nutrition counseling. Children should exercise for at least 60 minutes daily and should limit television and video games to less than two hours a day.

Because gastrointestinal adverse effects are common (but transient) with metformin therapy, the committee recommended starting with a low dose of 500 mg daily, increasing by 500 mg every one to two weeks, up to an ideal and maximum dose of 2,000 mg daily in divided doses.

Clinicians should start insulin therapy for children who are ketotic or in diabetic ketoacidosis and in whom the distinction between types 1 and 2 diabetes is unclear, the guidelines state. Otherwise, clinicians should start insulin for patients who have random venous or plasma blood glucose concentrations of 250 mg/dL or greater or those whose HbA1c level is above 9%. Those who lack evidence of ketosis or ketoacidosis may also benefit from short-term insulin, which provides quicker restoration of glycemic control and may allow islet β cells to "rest and recover." Insulin may also increase long-term adherence to treatment by enhancing the patient's perception of the seriousness of the disease, the guidelines said. Patients may later gradually be weaned from insulin and managed with metformin and lifestyle modification.

Clinicians should monitor HbA1c concentrations every three months and should intensify treatment if treatment goals for fingerstick blood glucose and HbA1c concentrations are not being met. Ideally, the HbA1c goal should be less than 7%, but goals must be achievable. "In addition, in the absence of hypoglycemia, even lower HbA1c target concentrations can be considered on the basis of an absence of hypoglycemic events and other individual considerations," the guidelines state.

Clinicians should tell patients who are taking insulin or other medications with a risk of hypoglycemia to monitor fingerstick blood glucose concentrations if they are starting or changing their diabetes treatment regimen, have not met treatment goals or have other illnesses.

Although normoglycemia may be difficult to achieve in teenagers, a fasting blood glucose concentration of 70 to 130 mg/dL is a reasonable target for most, the guidelines state. Because postprandial hyperglycemia has been associated with increased risk of cardiovascular events in adults, postprandial blood glucose testing may be valuable in select patients. Blood glucose concentrations taken before eating paired with readings taken two hours after meals may be useful in improving glycemic control, particularly for patients whose fasting plasma glucose is normal but whose HbA1c is not at target.

Primary care clinicians who are not confident that they can treat diabetes in children because of the child's age or coexisting conditions should refer the patient to a pediatric medical subspecialist, the guidelines advise.



Test yourself


.
MKSAP Quiz: Photocoagulation therapy

A 62-year-old man is evaluated before having panretinal laser photocoagulation therapy in both eyes. He has an 18-year history of type 2 diabetes mellitus. He also has diabetic neuropathy and hypertension. At his annual retinal eye examination last week, his vision had deteriorated to 20/30 in his right eye and 20/40 in his left eye; new blood vessels are seen growing on the optic discs of both eyes. Medications are metformin, insulin glargine, simvastatin, ramipril, enteric-coated aspirin, and hydrochlorothiazide.

On physical examination, temperature is 36.9 °C (98.4 °F), blood pressure is 147/86 mm Hg, pulse rate is 88/min, and respiration rate is 14/min; BMI is 34. Other than the presence of proliferative diabetic retinopathy, physical examination findings are unremarkable.

Which of the following is the most likely outcome of the planned procedure?

A. Diminished central vision with retention of peripheral vision
B. Diminished peripheral and night vision with retention of central vision
C. Improvement of vision (to 20/20) in both eyes
D. Loss of binocular vision and depth perception

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.



From ACP Journal Club


.
Hypoglycemia was associated with increased mortality in ICU patients regardless of glucose control strategy

A post hoc analysis of the NICE-SUGAR trial that included about 6,000 ICU patients compared intensive glucose control (targeting blood glucose levels of 81 to 108 mg/dL) and conventional glucose control (targeting levels ≤180 mg/dL). Intensive glucose control caused more moderate and severe hypoglycemia than conventional control. Hypoglycemia was associated with increased risk for 90-day mortality in the intensive and control groups.

The study was published by New England Journal of Medicine on Sept. 20. The following commentary by Todd W. Rice, MD, MSc, was published in the ACP Journal Club section of the Jan. 15 Annals of Internal Medicine.

Evidence of a direct association between iatrogenic hypoglycemia and mortality in critical illness, as shown in the NICE-SUGAR study, reinforces concerns about interventions to achieve tight glucose control. Findings from a seminal trial showing improved ICU survival with intensive insulin therapy have been refuted by more recent systematic reviews. It is likely that both severe hyperglycemia and hypoglycemia adversely affect ICU survival. A recent study of intensive insulin therapy in patients with sepsis was stopped early when the data monitoring committee observed increased hypoglycemia, with no measurable survival effect.

Historically, hypoglycemia in the ICU was perceived to be a marker of illness severity rather than a direct cause of mortality. The post hoc analysis of the NICE-SUGAR study supports both explanations. The association between hypoglycemia and mortality in the absence of insulin therapy suggests that hypoglycemia is a marker for sicker patients with a higher risk for death. However, the same association among patients receiving insulin therapy for hyperglycemia supports a causal link in this group. Mortality increased with the severity of hypoglycemia and also with an increasing number of hypoglycemic events.

These data show a complicated relation between hypoglycemia and mortality in critically ill patients. At the present time, a reasonable approach for treating critically ill patients with hyperglycemia is to use a moderate glucose control treatment algorithm, targeting 144 to 180 mg/dL, to minimize severe hyperglycemia and avoid iatrogenic hypoglycemia.


.
A single screening for type 2 diabetes in high-risk adults did not reduce mortality over 10 years

A trial in the United Kingdom randomized 33 primary care practices and 20,000 of their high-risk patients to screening for diabetes or usual care. Three percent of the screened patients were diagnosed with diabetes, and screening for type 2 diabetes did not reduce all-cause, cardiovascular (CV), cancer, or diabetes-related mortality compared with no screening.

The study was published by The Lancet on Nov. 17. The following commentary by Jeffrey Mahon, MD, MSc, was published in the ACP Journal Club section of the Jan. 15 Annals of Internal Medicine.

The unique feature of this well-done trial by Simmons and colleagues, and one that self-declared experts doubted was possible, was randomization of participants to diabetes screening or not. This is the best way to control biases that overinflate estimates of benefit in observational studies of screening. Other strengths include testing the question in a way that approximates how screening works in the messier circumstances of real-life clinical practice and near-complete ascertainment of the primary outcome.

If screening for type 2 diabetes reduces premature all-cause mortality, most of this probably occurs through earlier use of therapies proven or strongly suspected to prevent premature CV mortality in persons with unrecognized diabetes (e.g., statins; angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, especially in patients with nephropathy including microalbuminuria; smoking cessation; and metformin). The study by Simmons and colleagues had the power to reliably exclude a modest effect (about 25% relative risk reduction) of screening on CV mortality over 10 years. However, detection of smaller, but still important, reductions in CV deaths requires a larger sample, longer follow-up, or both. The authors also acknowledge that unmeasured factors could have eroded study power to detect mortality differences, including a lower risk for death in control participants, perhaps through improved vascular risk management (e.g., statin use), and opportunistic diabetes screening.

The lack of effects on mortality and CV mortality does not strengthen current recommendations by most major practice guideline groups to screen for diabetes. At the same time, the authors note that study limitations make it difficult to be sure that there were not (or will not be) clinically important benefits that justify the costs of early detection of diabetes under some circumstances. Diabetes screening will not disappear, although the standard for the type of evidence needed to endorse widespread screening may have just been reset.


.
Review: Intensive blood pressure control reduces stroke, but not mortality or MI, in type 2 diabetes

A meta-analysis compared five studies (including the ACCORD trial) that treated adults with type 2 diabetes with antihypertensive therapies to achieve prespecified blood pressure (BP) targets. Intensive BP targets were found to reduce stroke but not mortality or myocardial infarction (MI), and in the one trial that reported details of adverse events, the intensive group had higher rates of serious adverse events.

The study was published by Archives of Internal Medicine (now JAMA Internal Medicine) on Sept. 24. The following commentary by ACP Member Louise Moist, MD, was published in the ACP Journal Club section of the Jan. 15 Annals of Internal Medicine.

More intensive BP control was the goal for patients with diabetes until the recent ACCORD study reported minimal benefit and increased risk for harm.

The meta-analysis by McBrien and colleagues found no reduction in MI or mortality and a small reduction in stroke with intensive BP targets. In the 5 studies analyzed, BP targets varied in the intensive (SBP [systolic BP]< 120 mm Hg, DBP [diastolic BP] ≤ 75 to 80 mm Hg) and standard groups (SBP < 140 mm Hg, DBP ≤ 85 to 90 mm Hg), making conclusions difficult. Only 1 study (ACCORD-BP with target SBP < 120 mm Hg) robustly examined adverse events. No conclusions can be made about SBP targets between 120 and 140 mm Hg, a continued area of controversy in practice and current BP guidelines.

Overall, this meta-analysis does not add any new information beyond the ACCORD study and includes all of its limitations. Not all patients in these [randomized, controlled trials] had a diagnosis of hypertension, and in most the indication to treat was for cardiovascular protection. Accordingly, baseline BP varied substantially among studies. The authors report an association between baseline BP and effect of BP lowering, suggesting that the effect of BP lowering may be greater with higher baseline BP. This highlights an important practice point: BP targets differ from BP thresholds (the criteria used to decide when to initiate therapy), and both are important in management of hypertension and in the interpretation of the targets.

The analysis also does not inform us on important patient subgroups, including the elderly and patients with significant kidney disease and/or proteinuria. The results of this review cannot be extrapolated to these subgroups, which have higher risks for harm.

The review by McBrien and colleagues will probably not affect practice beyond the known results of the ACCORD study. It does not address SBP targets < 130 mm Hg, rather than < 120 mm Hg, and leaves opportunity for further studies to examine these unmet needs.



Tool of the month


.
Tips to help patients get the most from their insulin

The following information should be shared with patients to optimize their insulin therapy:

  • Take your insulin at the same time each day (unless the patient is on basal-bolus insulin, in which case the insulin is given before meals, whatever time they are eaten).
  • Take your insulin when you do other routine activities (e.g., eat meals, get ready for bed).
  • Unopened insulin can be safely stored in the refrigerator until the expiration date.
  • Opened vials of insulin can be safely stored at room temperature (less than 30 °C [86 °F]) for 28 to 30 days. If insulin freezes or is exposed to temperatures above 30 °C [86 °F]), it becomes completely ineffective and must be discarded.
  • Insulin pen cartridges have different expiration dates depending on the brand and type of insulin. Follow the manufacturer's instructions.
  • Syringes can be safely re-used if handled appropriately: Avoid touching the needle and replace the cap over the needle; move the plunger up and down to help prevent clogs; and do not wipe the needle with alcohol, as this removes the silicone coating. Smaller-gauge needles have fewer re-uses than larger-gauge needles before becoming painful.
  • Provide information regarding appropriate needle disposal for the patient's community based on local regulations.

From the ACP Diabetes Care Guide.



Keeping tabs


.
Spotlight on insulin timing

The timing of insulin injections for patients with type 2 diabetes was the focus of several studies published in the past month.

A randomized crossover study assessed whether it is necessary to wait 20 minutes after injecting insulin before eating. The trial, published by Diabetes Care on Jan. 22, included 100 German patients with type 2 diabetes who injected insulin 20 minutes before eating in one phase of the trial and injected insulin immediately before eating in the other phase. Their average hemoglobin A1c (HbA1c) increased by only about 0.08% when they didn't wait to eat, and rates of hypoglycemia were similar. Patients were more satisfied with treatment in the no-wait phase and 86.5% said they preferred it. Researchers noted that the study didn't assess the effects of 30-, 45- or 60-minute waits, but they concluded that a 20-minute interval is not necessary and could potentially reduce the problem of patients forgetting injections.

Another study, published by Diabetes Care on the same day, included about 600 type 2 diabetes patients randomized to once-daily insulin degludec with their evening meal, once-daily insulin glargine at the same time each day, or a pre-set schedule of insulin degludec with large variations in the interval between doses (between 8 and 40 hours). After 26 weeks, HbA1c levels had improved by similar amounts in all three groups, and similar rates of hypoglycemia and adverse events were seen. The highly variable dosing schedule is not recommended for clinical practice, but the study shows that varying the time of injections doesn't compromise glycemic control, the study authors said. This finding may be useful for, and improve compliance by, patients with changing schedules, they suggested.

A third study, published by the new journal The Lancet Diabetes & Endocrinology on Feb. 2, looked at the timing of insulin use in the overall course of diabetes. Researchers conducted a systematic review of seven studies that treated newly diagnosed type 2 patients with intensive insulin therapy. They found that the therapy increased patients' β cell function by 13% and decreased their insulin resistance by 43% (as measured by Homeostasis Model Assessment). Four of the studies assessed diabetes remission rates and found that 42.1% patients were in remission 24 months after therapy. The patients who achieved remission had higher body mass index and lower fasting plasma glucose at baseline, which might present a way to target the insulin strategy at the patients most likely to benefit, the authors said. An accompanying comment noted that all of the studies were conducted in China and Taiwan, so further investigation is warranted before applying the findings to practice in other settings.


.


MKSAP Answer and Critique



The correct answer is B. Diminished peripheral and night vision with retention of central vision. This item is available to MKSAP 16 subscribers as item 1 in the Endocrinology section. Part A of MKSAP 16 was released on July 31, 2012 and Part B on Feb. 1, 2013. More information is available online.

This patient will most likely have diminished peripheral and night vision but retained central vision after photocoagulation. Panretinal laser photocoagulation delivers several thousand small burns to the periphery of the retina, which results in the avascular scarring and shriveling of new vessels shown.

As a result, more retinal blood flow is available for the central part of the retina, which helps retain central vision. However, this procedure also causes deterioration of peripheral vision, which often is most noticeable at night.

This patient's overall visual acuity is unlikely to improve but should not get significantly worse, unless the proliferative retinopathy progresses.

Because central vision remains intact, neither binocular vision nor depth perception will be affected.

Key Point

  • Panretinal laser photocoagulation therapy for diabetic retinopathy typically results in retained central vision but poorer peripheral and night vision.

Click here to return to the rest of ACP DiabetesMonthly.

Top




About ACP DiabetesMonthly

ACP DiabetesMonthly is a monthly newsletter produced by the staff of ACP Internist. It is automatically sent to all College members who have an e-mail address on file with ACP.

To add your e-mail address to your member record and to begin receiving ACP DiabetesMonthly, please click here.

Copyright © by American College of Physicians.

Test yourself

A 69-year-old woman is evaluated for a lump under her arm found on self-examination. She is otherwise healthy and has no other symptoms. Medical and family histories are unremarkable, and she takes no medications. A needle aspirate of the right axillary mass reveals adenocarcinoma. Bilateral mammography and breast MRI are normal. CT scan of the chest, abdomen, and pelvis demonstrates the enlarged axillary lymph node and no other abnormalities. What is the most appropriate initial treatment?

Find the answer

What will you learn from your Annals Virtual Patient?

Reviews of the World's Top Medical Journals—FREE to ACP Members! Annals Virtual Patients is a unique patient care simulator that mirrors real patient care decisions and consequences. CME Credit and MOC Points are available. Start off with a FREE sample case. Start your journey now.

Products and Resources for Patients

Products and Resources for PatientsACP has developed easy- to-use materials designed to help educate your patients on self-management of a wide variety of common health conditions. Order yours today!