Potential Upcoming Shifts for Diabetes-Related Diagnostic Testing

New research suggests that potential shifts might occur in diabetes-related testing, including potential increased use of point-of-care- (POC-) based hemoglobin A1c (HbA_1c) testing for systematic screening and genetic testing in select patients diagnosed with diabetes.

Point-of-Care Testing Aids Identification of Prediabetes
Systematically screening patients with POC-based HbA_1c testing is more effective than standard screening practices at identifying patients with undiagnosed prediabetes, according to a study published in the March/April issue of the Annals of Family Medicine.

Given the American Diabetes Association’s estimate that more than 8 million Americans may be living with undiagnosed diabetes, experts say there is a need to more quickly and easily identify and treat patients with hyperglycemia in order to improve outcomes. Standard practice uses fasting blood glucose tests in select patients. This test is known to be inconvenient and possibly delays care because of difficulty with patient follow-up.

The present study compared the number of diabetes screenings and test results between patients tested under standard practice and those systematically offered POC HbA_1c tests among patients aged 45 years or older being seen in a single-physician family medicine clinic. Patients with scheduled appointments on Tuesdays (active screening arm; offered a free POC HbA_1c test; n=164 screened and included in final analysis) were compared to those with a Wednesday appointment (standard practice arm; assessed for diabetes screenings under usual care; n=324 patients included in final analysis). Appointments occurred between April 2013 and March 2014. A clinical pharmacist evaluated patients in the office. Both groups were predominately obese.

Of the 164 participants that were systematically screened participants, 63 percent were diagnosed with previously unknown hyperglycemia. In total, 53 percent of the systematically screened had prediabetes (HbA_1c 5.7%-6.4%) and 10 percent had had diabetes (HbA_1c more than 6.5%). A mong the 324 patients in the standard practice arm, 22 percent (n = 73) were screened, primarily by blood glucose (96 percent). Of those tested 8 percent had diabetes and 33 percent had prediabetes. The association between screening outcome and screening method, the researchers report, was statistically significant, in favor of HbA_1c.

“HbA_1c may be a superior screening method, due to effectively identifying individuals early on in the course of the disease, which accounts for this study’s difference in identified hyperglycemia,” writes lead author Heather Whitley, Pharm.D., from Auburn University in Alabama. “Identifying and treating chronic hyperglycemia early can result in clinically meaningful patient outcomes, which is most feasible by HbA_1c screenings and further facilitated by POC devices.”

Genetic Causes of Diabetes Not Considered
Monogenic forms of diabetes remain misdiagnosed and often inappropriately treated, according to a presentation at the American College of Medical Genetics and Genomics’ (ACMGs’) Annual Clinical Genetics Meeting (Phoenix; March 22-24).

These cases of diabetes, caused by a single gene defect, represent a heterogeneous group of disorders. While the actual prevalence of monogenic diabetes is not known, it is estimated to account for one to five percent of all diabetes cases. Experts say a majority of these cases go unrecognized or misdiagnosed as type 1 or type 2 diabetes and are often inappropriately treated.

The U.S Monogenic Diabetes Registry was created in 2008 at the University of Chicago to collect genetic, medical, and clinical information about monogenetic diabetes to further understanding of the disorder and raise awareness about the condition. As of December 2016, the registry enrolled 1,349 families, which were profiled in the ACMG presentation.

Genetic testing was initially performed via Sanger sequencing (for pathogenic variants in GCK, HNF1A, HNF4A, INS, and KCNJ11) and with a targeted, next-generation sequencing panel for those negative using Sanger sequencing. Pathogenic causes were identified in 429 families (674 individuals). For the three categories of monogenic diabetes common mutations were identified. For permanent neonatal diabetes, KCNJ11 (14.7 percent), INS (6.3 percent), and ABCC8 (5.4 percent) were the most common causes. For maturity onset diabetes of the young (MODY), mutations in GCK were most common (42 percent), followed by HNF1A (17.5 percent), and HNF4A (3.6 percent).

The majority of the registry participants were genetically diagnosed on a research basis. Although in many cases, there was a significant delay (more than 10 years) from initial diabetes diagnosis to confirmation of a monogenic cause.

“This delay in diagnosis can be primarily explained by two factors: 1) lack of physician awareness of the different subtypes of monogenic diabetes, how to clinically diagnose, and request genetic testing; 2) inadequate insurance coverage or refusal of insurance companies to cover genetic testing,” says presenter May Sanyoura, Ph.D., from the University of Chicago (Illinois). “Monogenic diabetes should be considered in any diabetic patient who has features inconsistent with their current diagnosis or presents with additional features characteristic to a specific syndromic subtype of monogenic diabetes.”

Of the MODY positive probands with the most common mutations, more than 27 percent were misdiagnosed at type 1 diabetes, 47.2 percent were misdiagnosed as type 2 diabetes, and more than 50 percent of them were inappropriately treated with either insulin or other glucose-lowering agents. For those diagnosed with the most common variants associated with neonatal diabetes, 45 percent of probands were misdiagnosed as having type 1 diabetes. An accurate diagnosis of monogenic forms of diabetes is “one of the most compelling clinical examples of personalized genetic medicine,” Sanyoura says, as certain mutations are linked to more effective management with certain treatments.

Takeaway: New research highlights potential shifts in diabetes-related testing, including potential increased use of POC HbA_1c testing for systematic screening and genetic testing in select patients diagnosed with diabetes.