Insulin resistance slows nerve regeneration in T2D patients on intensive glycaemic control

11 Jun 2021

Insulin resistance (IR) seems to limit nerve regeneration and neuropathy improvement among type 2 diabetes (T2D) patients undergoing intensive glycaemic control, a new study has shown.

The study included 38 T2D patients (mean age 50.2±8.5 years, 60 percent men) enrolled from an open-label, randomized controlled trial. All participants were receiving treatments to achieve and maintain glycated haemoglobin (HbA1c) levels <7.0 percent. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was used as a surrogate for IR. Neuropathy was assessed using corneal confocal microscopy.

At the 1-year follow-up, HbA1c dropped significantly, from 10.7 percent at baseline to 7.9 percent (p<0.0001). Diastolic blood pressure (p<0.0001), total cholesterol (p<0.01), and low-density lipoprotein cholesterol (p=0.05) were all likewise reduced by follow-up, though no such effect was reported for systolic blood pressure, body mass index, and triglyceride level.

Over the same time span, corneal nerve branch density (CNBD; p<0.01) and fibre length (CNFL; p<0.05) grew significantly, while fibre density (CNFD) increased nonsignificantly (p=0.26).

Of the participants, 65.8 percent (n=25) and 34.2 percent (n=13) had HOMA-IR ≥1.9 and <1.9, respectively. Those in the latter subgroup saw a significant increase in CNFL, CNBD, and CNFD (p≤0.01 for all), while those in the former experienced no such changes.

Linear regression analysis revealed an inverse correlation between baseline HOMA-IR, as a continuous variable, and the change in CNFD (p<0.05). Each 1-unit increase in HOMA-IR corresponded with a 1.38-fibres/mm2 drop in CNFD. No such interaction was detected for changes in CNBD and CNFL.

“[T]his study found that patients with T2D and IR show blunted small nerve fibre regeneration despite a substantial improvement in glycaemic control,” the researchers said. “Therefore, lifestyle interventions, such as physical activity and weight reduction to improve IR may benefit diabetic peripheral neuropathy (DPN).”

“Furthermore, IR should be considered as a potential confounder when assessing the benefits of disease modifying therapies in clinical trials for DPN,” they added.

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