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Advanced glycation end product accumulation, insulin resistance share 'two-way' relationship

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February 21, 2019

Insulin resistance and the accumulation of advanced glycation end products in the skin have a “two-way” relationship for adults with type 1 diabetes, according to findings published in Diabetic Medicine.

“Skin autofluorescence has been shown to be higher in people with diabetes than in healthy controls, and it also correlates with the results of [advanced glycation end product] accumulation in skin biopsies and with HbA1c levels,” Aleksandra Uruska, MD, PhD, of the department of internal medicine and diabetology at Poznan University of Medical Sciences in Poland, and colleagues wrote. “Moreover, skin autofluorescence is related to the development and progression of chronic diabetic complications.”

Uruska and colleagues consecutively recruited 476 adults with type 1 diabetes (median age, 42 years) from the department of internal medicine and diabetology at the Poznan University of Medical Sciences in Poland to assess the association between skin autofluorescence and estimated glucose disposal rate (eGDR), which was used as an analogue for insulin resistance and sensitivity.

The researchers collected fasting blood samples from each participant, using the samples to measure plasma glucose, total cholesterol, HDL cholesterol, triglyceride levels, LDL cholesterol, HbA1c and estimated glomerular filtration rate. In addition, an advanced glycation end product (AGE) reader was used to measure skin autofluorescence three times, with measures taken on the ventral site of the forearm. The mean of the three measurements was used for analysis.

Insulin resistance and sensitivity were determined via an equation created by the researchers for eGDR, with lower eGDR denotating higher insulin resistance. After these measurements, three subgroups were formed. The first was for participants with eGDR of less than 5.5 mg/kg per minute, the second was for participants with eGDR of 5.5 mg/kg per minute to 9 mg/kg per minute, and the third was for participants with eGDR of more than 9 mg/kg per minute.

Roughly half of all participants had low insulin sensitivity, which was defined as eGDR of less than 7.4 mg/kg per minute. As eGDR increased, skin autofluorescence decreased (P < .0001). According to the researchers, this information provided evidence of a negative correlation between AGEs and eGDR (P < .0001). They added that this association was “two-way” based on multiple logistic regression models.

“This relationship is certainly bidirectional, with both pathogenic processes mutually influencing each other. ... This vicious circle increases the risk of diabetic angiopathy and worsens the prognosis for people with type 1 diabetes,” the researchers wrote. “To improve prognosis in type 1 diabetes, it is extremely important to maintain good metabolic control from the beginning of the disease in order to prevent the development of insulin resistance; however, further research is needed to determine if insulin resistance can be influenced by decreasing AGE formation and if lowering AGE accumulation can improve insulin sensitivity.” – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.

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