Laser-Doppler-Imager Flare Detects Early Diabetic Neuropathy

Miriam E. Tucker

September 24, 2014

The "laser-Doppler-imager (LDI) flare" may represent a new method for detecting early small-nerve-fiber changes in people with diabetes, according to the first year of results from a prospective study.

The findings were presented September 14 at Neurodiab, the annual meeting of the Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes, by Sanjeev Sharma, MD, specialist registrar (endocrinology and diabetes) at the Diabetes Centre, Ipswich Hospital NHS Trust, Ipswich, United Kingdom. The chief investigator for this study was Gerry Rayman, MD, also from the Diabetes Centre, Ipswich Hospital NHS Trust, who has pioneered this technique and supervised the trial.

Initially developed as a method to evaluate vascular perfusion, the LDI flare is under study as a noninvasive method for assessing small-fiber function.

It uses a dual-wave laser scanner to measure the axon-reflex–mediated hyperemic response in the foot skin after heating sequentially up to 47°C using a 1-cm2 heating probe. The flare response — the area surrounding a heated central region — is impaired in patients with early neuropathy compared with those without neuropathy.

In this new study of 80 patients with type 1 diabetes, 82 with type 2 diabetes, and 80 healthy controls, the LDI-flare response distinguished between subjects with and without diabetes, and at 1 year correlated with changes in triglycerides and HbA1c in the diabetes patients.

Dr. Sharma told Medscape Medical News that the LDI flare has already been shown to have "excellent" reproducibility and correlates significantly with measures of small-fiber neural function, including intra-epidermal-nerve–fiber density and in vitro confocal microscopy. At the same time, its advantages include being noninvasive (as compared with nerve biopsy) and requiring minimal specialist training, in contrast to confocal microscopy.

"Usual bedside assessments for diabetes neuropathy can be normal in early cases," he explained. "The LDI-flare technique not only improves our understanding of the mechanisms of diabetes polyneuropathy but also provides an option for assessing early neuropathy and painful diabetes neuropathy, based on which diabetes care can be appropriately directed."

Commenting on the study, session moderator Dr. Dinesh Selvarajah, senior lecturer, clinical diabetes consultant physician, Sheffield Teaching Hospitals Foundation Trust, United Kingdom, told Medscape Medical News: "LDI flare is a potentially useful technique to examine small-fiber function in patients with diabetes."

"This is the first prospective study using the LDI-flare technique to examine the long-term reproducibility and predictive capability of this method to assess neuropathy risk in patients with diabetes. They presented the baseline and 1-year follow-up data. So it is still too early to come up with firm conclusions on this promising technique."

Following the Flare

At 1 year, the LDI-flare size (ie, small-fiber function) compared with baseline was reduced by 6.8% in the type 1 diabetes patients and by 5.9% in the type 2 patients, compared with just 0.84% among the healthy controls (P < 0.001 for both diabetes groups vs controls).

Among the type 1 diabetes patients, the percent reduction was significantly greater among the 56 with microangiopathy compared with the 24 without microangiopathy (8.7% vs 4.6%; P < .0001). However, there was no significant difference between the 49 type 2 diabetes patients with microangiopathy and the 33 without (4.9% vs 6.0%; P = .06).

Dr. Sharma told Medscape Medical News the differences in findings between the type 1 and type 2 diabetes patients can be explained on the grounds of pathogenesis of small-fiber dysfunction, which is different between the 2 groups.

"While type 2 diabetes is more related to metabolic syndrome, where insulin resistance plays an important part, the same cannot be said of type 1, where glycemic control plays an important role in the genesis of small-fiber neuropathy."

There was a highly significant correlation between triglycerides and LDI-flare size in both the controls and the diabetes patients (both types) at baseline (P = .008 and .001, respectively) and at year 1 (P = .01 and .004, respectively). And the change in triglycerides also correlated with change in LDI-flare size (P = .008 and .009, respectively).

"There is increasing evidence to suggest that triglycerides play an important role in the pathogenesis of diabetes polyneuropathy. This relationship is so far shown in various cross-sectional studies to be independent of glycemic control. Our prospective 1-year study shows the same positive correlation, but by showing this in a prospective study, we can prove a stronger association compared with cross-sectionally designed studies," Dr. Sharma explained.

Change in small-fiber function as measured by LDI flare did not correlate with body mass index (BMI), other lipid indices, or blood pressure. Neuropathy disability scores, sural-nerve amplitude, and sural-nerve conduction velocity did not change over the study year, nor did they correlate with changes in HbA1c, lipids, or blood pressure, he added.

"Although these are findings for only the first year of our prospective study and might change later," the LDI-flare estimates small-fiber function, and variables such as BP, BMI, and other lipid indices are better known to affect large-fiber parameters, "but we will have to confirm this hypothesis in the future," he told Medscape Medical News.

Which Neuropathy Test Is Best?

Dr. Sharma said his group has tweaked the original LDI-flare equipment to make it easier to use.

"With our modifications, we have been making the technique simpler, less time-consuming, and requiring only a moderate level of operator training. Ideally, we would like the technology to be reduced to a simple handheld device to improve its applicability in larger populations."

Dr. Selvarajah told Medscape Medical News, "The investigators have worked on making this test more user- and patient-friendly, reducing the time to complete the test and examining the clinical utility in children and young adults with diabetes."

He said that currently there are several devices "all vying to be the leader in the field of point-of-care devices for the early detection of neuropathy," and that they lie on a spectrum: on the one end are tools that are "easy to use and suitable for large-scale epidemiological/clinical screening studies" such as Neuropad (TRIGOcare International) and devices from Sudoscan and Neurometrix. On the other end are tools that are "more detailed, for careful phenotyping of diabetic neuropathy patients," such as LDI-flare and corneal confocal microscopy.

"We are fortunate to have these options available and await these long-term prospective studies to determine the most useful clinical context," Dr. Selvarajah concluded.

Dr. Sharma and Dr. Selvarajah have reported no relevant financial relationships.

Neurodiab. September 14, 2014; Sopron, Hungary. Abstract O-41.

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