Blood sugar swings or fluctuations may considerably increase the risk of neuropathy (nerve damage) in people with type 2 diabetes, a new study has reported.
According to the findings, fluctuation in fasting blood sugar was the leading risk factor for neuropathy.
Neuropathy is a common microvascular (small blood vessel) complication of diabetes, resulting from long-term exposure of the nerve cells to high blood sugar levels. There are four main types of neuropathy – peripheral, sensory, autonomic and motor. Peripheral neuropathy is the most common; it affects the nerves in the feet and hands and can cause a loss of sensation and movement defects.
Current American Diabetes Association (ADA) guidelines recommend the following blood sugar targets to minimise the risk of complications such as neuropathy: glycated haemoglobin (HbA1c) less than 7%, a fasting blood glucose of 80-130 mg/dL (4.4-7.2 mmol/L), post-meal blood glucose of <180 mg/dL (10 mmol/L) and blood sugar variability of ≤ 36%. Of note, blood sugar variability refers to blood swings occurring throughout the day, including hypoglycaemic episodes and post-meal rises and day-to-day- changes.
Past research has associated diabetes duration, insulin resistance, abdominal fat, high blood pressure and abnormal blood fat with peripheral neuropathy development. However, others show that persistent high blood sugar and short-term blood sugar swings from high to low levels increase its risk. Few studies have investigated the link between blood sugar fluctuations and peripheral neuropathy in large cohorts over long-term follow-ups.
Researchers followed 1152 adult patients [mean age 62, 50.89% male] between February 2010 and December 2020. All patients had at least four annual medical reviews with measurements of height, weight, and blood pressure. Researchers also assessed their blood sugar (glycated haemoglobin [HbA1c], fasting blood sugar, two-hour post-meal blood glucose), blood fat profile (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C] and triglyceride), and kidney function [urinary creatinine excretion].
Blood sugar levels are higher and fluctuate more in people with diabetic neuropathy
A total of 334 patients developed neuropathy over the 10-year follow-up. These patients had a longer duration of diabetes and higher fasting blood sugar, two-hour post-meal blood sugar, HbA1c, cholesterol, creatinine and albuminuria than those without neuropathy. Of note, albuminuria is the presence of abnormal albumin protein levels in the urine. Sex, smoking status, insulin use, and history of high blood pressure did not affect neuropathy risk, but variations in cholesterol, creatinine and albuminuria were associated with higher risks.
Patients with neuropathy also had significantly higher fluctuations in HbA1c, fasting and two-hour post-meal blood sugar, with fasting blood sugar fluctuations identified as the top risk factor for neuropathy. Specifically, variations of 10% and 20% in fasting blood sugar, 5% and 10% in HbA1c and 20% in two-hour post-meal blood sugar were significantly associated with neuropathy development.
The researchers proposed a relationship between blood sugar variations and neuropathy, stating that long-term blood sugar fluctuations generate “oxidative stress” – an imbalance between the production of harmful free radicals and neutralising antioxidants – leading to the activation of inflammatory pathways that damage blood vessels.
They highlighted several limitations of the study, including no formal testing of neuropathy and the inclusion of primarily middle-aged participants with prolonged diabetes and long-term complications.
“Our study demonstrates that FBS [fasting blood sugar], 2hPP [2-hour postprandial glucose], total cholesterol and creatinine variability are significantly higher in DPN-developed diabetic patients,” the researchers wrote.
“Further studies are required to establish the biological mechanisms beneath the glycaemic [blood sugar] variability and DPN [diabetic peripheral neuropathy], they wrote.