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Rate of HbA1c increase influences risk for diabetic polyneuropathy

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July 17, 2018

Among adults with type 2 diabetes, each 1% increase in HbA1c during 10 years increases the risk for diabetic polyneuropathy by nearly 66%, according to data from the ADDITION-Denmark study published in Diabetes Care.

“Hyperglycemia is considered the most important risk factor for the development of diabetic polyneuropathy in type 1 diabetes,” Signe T. Andersen, a doctoral fellow with the department of public health, Aarhus University, Denmark, and colleagues wrote in the study background. “A more complex risk factor profile exists for [diabetic polyneuropathy] in type 2 diabetes, as intervention trials have failed to show a clear effect of enhancing glucose control on the risk of [diabetic polyneuropathy].”

In the nested case-control analysis, Andersen and colleagues evaluated data from 452 participants who attended the 13-year follow-up visit for ADDITION-Denmark, a study of adults aged 40 to 69 years with screen-detected, previously undiagnosed diabetes via stepwise screening in primary care between 2001 and 2006 (median age, 71 years; 62.2% men; 94.5% white). In ADDITION-Denmark, researchers randomly assigned participating general practices to deliver either routine care for diabetes or intensive, multifactorial, target-driven care until 2009. Researchers followed participants observationally via questionnaires, registers and a clinical follow-up assessment in 2015-2016.

Researchers assessed diabetes risk factors at diagnosis and 6 and 13 years, including HbA1c, total cholesterol, HDL cholesterol, triglycerides, creatinine and albumin-to-creatinine ratio, and performed a nested case-control analysis comparing risk-factor levels and changes (trajectories) between those who developed diabetic polyneuropathy at follow-up (cases) and those without diabetic polyneuropathy (controls). Within the cohort, 27% had diabetic polyneuropathy and 4.9% had subclinical diabetic polyneuropathy at follow-up. Of the control group participants, 193 (59%) had potential or probable diabetic polyneuropathy.

In assessing risk for diabetic polyneuropathy, there were no between-group differences when stratified by sex (OR = 0.46; 95% CI, 0.46-1.13) or trial randomization group (OR = 1.15; 95% CI, 0.76-1.73). Greater risk for diabetic polyneuropathy was associated with advanced age (OR = 1.08; 95% CI, 1.04-1.13 per year of age), longer duration of diabetes (OR = 1.14; 95% CI, 1-1.3 per year) and being taller (OR = 1.06; 95% CI, 1.03-1.1 per cm), according to researchers.

Researchers found that diabetic polyneuropathy was associated with both a higher modeled baseline HbA1c (OR = 1.76; 95% CI, 1.37-2.27 per 1% increase during 10 years), as well as a sharper HbA1c increase over time (OR = 1.66; 95% CI, 1.21-2.28 per 1% increase during 10 years).

Diabetic polyneuropathy was also correlated with higher baseline weight (OR = 1.2; 95% CI, 1.1-1.31 per 5 kg), waist circumference (OR = 1.27; 95% CI, 1.13-1.43 per 5 cm) and BMI (OR = 1.24; 95% CI, 1.12-1.38 per 2 kg/m2). Conversely, sharper increases in total cholesterol over time were linked to lower risk of diabetic polyneuropathy (OR = 0.83; 95% CI, 0.70-0.99 per 0.5 mmol/mol during 10 years).

“This study indicates that the rate of increase in HbA1c affects the development of [diabetic polyneuropathy] over and above the effects of the baseline level of HbA1c, even within ranges considered well-controlled,” the researchers wrote. “Higher baseline levels of HbA1c and higher obesity levels were associated with higher risk of [diabetic polyneuropathy].” – by Jennifer Byrne

Disclosures: The authors report no relevant financial disclosures.

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