KidsADA Lowers Recommended HbA1c Target in Children
In a recent position statement, the American Diabetes Association (ADA) lowered its recommended HbA1c target for children with type 1 diabetes, to 7.5% across all pediatric age groups (Diabetes Care 2014; doi:10.2337/dc14-1440). The change puts ADA’s recommended target in line with those of three other clinical societies, including the International Society for Pediatric and Adolescent Diabetes, the Pediatric Endocrine Society, and the International Diabetes Federation.

ADA’s old targets had been age-specific, with higher targets for younger children. Those recommendations had been based on two lines of scientific literature, reflecting “unsubstantiated evidence,” according to the ADA. One was based on insulin therapy in the “pre-modern era” in which patient-friendly blood glucose monitors, continuous glucose monitoring, and the like did not exist and assumed that severe hypoglycemia would lead to neurocognitive dysfunction, especially in younger children. The other line of literature was skeptical about any impact blood glucose and HbA1c levels prior to puberty might have on the risk of developing long-term diabetes complications. The age-based targets also reflected the reality of maintaining tighter glycemic control in younger children given their physiological development and behavioral challenges in this regard.

However, ADA now asserts that emerging evidence necessitates a change. Modern treatment tools and strategies, along with “active 
ongoing research have dispelled concerns regarding hypoglycemia and neurocognitive dysfunction,” the statement notes. In addition, “burgeoning evidence” indicates that elevated blood glucose and HbA1c levels may adversely affect short-term neurocognitive and central nervous system function in children.

“The evidence shows that there is a greater risk of harm from prolonged hyperglycemia that would occur if children maintained an A1c of 8.5 percent over time. This is not to say we are no longer concerned about hypoglycemia, but we now have better tools to monitor for hypoglycemia,” said one of the statement’s authors, Jane Chiang, MD, senior vice president of medical and community affairs at ADA.

ADA acknowledged that rigorous evidence for the recommendation does not currently exist. Still, the change is based on clinical studies, clinical experience, and intensive management strategies designed to achieve near-normal glycemic control without triggering hypoglycemia.

The statement also recommended that HbA1c testing occur routinely, and be performed by laboratories that use methods certified by the National Glycohemoglobin Standardization Program and standardized to the Diabetes Control and Complications Trial method.

Electronic Hard Stop on Duplicate Tests Saves Money, With no Effect on Patient Safety
A pilot project at the Cleveland Clinic demonstrated that a clinical decision support tool (CDST) used with the Clinic’s computerized physician order entry (CPOE) stopped 11,790 orders for unnecessary duplicate tests and saved the institution $183,586 in 2 years (Am J Clin Pathol 2014;141:718–23). The project was spearheaded by Cleveland Clinic’s test utilization committee, a multidisciplinary task force, which reports to and is supported by the organization’s senior leaders.

The project grew out of an earlier effort that involved adding a so-called soft stop CDST to the CPOE in which ordering physicians would be alerted that they were about to order a duplicate test, but allowed to continue the order. This proved effective in reducing duplicate orders for expensive molecular diagnostics by specialty physicians, but not so with more routine tests. These results prompted the test utilization committee to explore a CDST that would completely block duplicate orders for selected tests. The final list included 1,259 tests that only could be ordered once a day; however, clinicians still could override the CDST by calling the lab’s client services area, and explaining why they wanted the duplicate test. This happened only 414 times, involving just 3% of duplicate orders.

In addition to monitoring the economic impact of the pilot, the test utilization committee evaluated CDST’s impact on patient safety. An analysis of Cleveland Clinic’s safety event reporting system found no untoward events or patient safety concerns.

Long-term Glycemic Control Lowers ESRD Risk in Patients with Baseline Diabetic Nephropathy 
Type 1 diabetics with proteinuria were able to slow down estimated glomerular filtration rate (eGFR) declines and markedly lessen their likelihood of developing end stage renal disease (ESRD) by controlling their HbA1c levels (J Am Soc Nephrol 2014; doi:10.1681/ASN.2013091002). The authors conducted the study to assess the long-term impact of improved glycemia in patients who already have diabetic nephropathy.

Although prior studies have demonstrated that improved glycemia prevents development of microalbuminuria and of impaired renal function, studies of its effect on patients with proteinuria at baseline have not been long enough or large enough to clearly address the effect of improved glycemia, according to the authors.

The study involved 349 patients with chronic kidney disease stages 1–3 who developed proteinuria between 1990 and 2004 and were followed until 2011. After 5 years, the investigators found no significant difference in eGFR decline between patients who had seen their HbA1c rise versus those whose HbA1c had lowered. Differences only emerged after 10 to 15 years.

Patients who had experienced a decrease in HbA1c were much less likely to experience ESRD after 15 years than those who had experienced either no change or an increase in HbA1c levels. Participants who experienced a decrease had a cumulative 29% risk of ESRD, while those with no change or an increase had a 42% risk.

Daily Metabolite Rhythms Documented
Ametabolomic study of healthy subjects under controlled lab conditions found clear daily rhythms of most metabolites with 24 hours’ wakefulness mainly reducing the magnitude of most metabolites (Proc Nat Acad Sci 2014; doi/10.1073/pnas.1402663111). The findings further the understanding of sleep and wake regulation and their associated metabolic processes, and will be vital when using metabolic profiling to identify robust biomarkers for disease states and drug efficacy, according to the authors.

The investigators took specimens from 12 male participants every 2 hours during a 48-hour period—including a 24-hour wakeful period—and analyzed them using liquid chromatography mass spectrometry. They tested 171 targeted and untargeted metabolites and found daily rhythms in 109. Among the latter, 78 maintained their rhythmicity during the subjects’ 24-hour wakefulness.

Metabolites most altered during sleep deprivation included lipids and acylcarnitines, serotonin, tryptophan, and taurine, with all increasing during sleep deprivation. Three-quarters of amino acids analyzed did not vary significantly with time of day. However, at least seven, including glutamate, proline, and valine had 24-hour rhythms irrespective of how much sleep or wakefulness the subjects experienced or the timing of their meals.

Pregnant bellyTargeted TSH Testing in Pregnancy Ineffective 
Aretrospective study in Sweden found about the same prevalence of trimester-specific elevated thyroid stimulating hormone (TSH) levels in pregnant women who underwent targeted testing and in those who had not been tested during pregnancy (Obstet Gynecol 2014;124:105). Furthermore, targeted testing missed more than 80% of pregnant women with elevated TSH. Based on these findings, the authors concluded that targeted thyroid testing is unsatisfactory.

The study took place in Uppsala County, Sweden, and involved blood samples collected in conjunction with routine ultrasound screening in weeks 17–19 of pregnancy. Altogether, the study included samples from 5,254 women. Researchers reviewed 
medical records to identify women who had thyroid testing during pregnancy, a total of 891. They also randomly selected for TSH and free T4 analysis 1,006 samples from women who were not originally targeted for screening.

The investigators found that about the same percentage of women—approximately 12%—in both the targeted and randomly selected cohorts had elevated TSH levels. Likewise, there was not a significant difference in the percentage of women who had overt hypothyroidism, 1.1% in the targeted test group and 0.7% in the randomly selected group. Of note, targeted testing missed 80% of pregnant women with elevated TSH levels.

The similar prevalence of elevated TSH in both groups—much higher than has been commonly reported—could be due to a population somehow more affected than others or unrealistically low trimester-specific TSH levels for the study population, according to the authors. They suggested that trimester-specific TSH levels for each laboratory probably would help detect women most likely to benefit from levothyroxine treatment.