Skin Autofluorescence: Noninvasive Diabetes Tool?

Skin autofluorescence may be a new, noninvasive technique to assess risk of cardiovascular and renal impairment in T1DM, according to a study published online in Cardiovascular Diabetology.¹

The study is the first to show a link between skin autofluorescence and incidence of macrovascular events in T1DM. However, results also showed that past macrovascular events remain the most important factor for predicting future risk.

“Skin autoflurescence that is strongly related to tissues biopsy levels of AGEs [advanced glycation end products], has value for predicting cardiorenal outcome in our patients with T1D. This relation is independent of the usual risk factors, which supports that long-term accumulation of AGEs in tissues contributes to diabetic complications, especially nephropathy,” wrote lead author Vincent Rigalleau of the University of the Antilles (Guadaloupe, France and INSERM, Bourdeaux, France), and colleagues.

AGEs may contribute to cardiovascular and renal risk through the promotion of inflammation and endothelial dysfunction. They can either be ingested from food, or produced in the body during periods of hyperglycemia and oxidative stress. In individuals with chronic kidney disease, decreased clearance of AGE precursors may also lead to AGE accumulation.

AGEs can also accumulate in the skin, but current analysis of skin AGEs requires skin biopsies which can be time-consuming and undesirable to patients. Past studies have suggested that skin autofluorescence correlates with concentrations of skin AGEs, and may provide a noninvasive way to measure skin AGEs.²  Prior results from this study have linked skin autofluorescence to retinopathy, nephropathy, and long-term glucose control. As such, skin autofluorescence may be an indication of “metabolic memory,” according to the authors. 

The study took place during 2009, and included 243 patients with T1DM (mean age 51.2 years, 58.9% men, mean duration of diabetes 21.4 years). Twenty-four participants (9.9%) had a history of microvascular events, and 53 (22.8%) had CKD at baseline. Researchers measured skin autofluorescence at baseline using the AGE reader SU 2.3 (DiagnOptics BV, Groningen, The Netherlands). At baseline and four years later, they evaluated macrovascular events (MI, stroke, gangrene, revascularization procedure for coronary, carotid or lower limb arteries), estimated glomerular filtration rate (eGFR), and urinary albumin excretion rate (AER).

Key results at four years:

• Macrovascular events: Significantly associated with higher skin autofluorescence (P=0.003)

♦ Skin autofluorescence was linked to almost five times increase odds of macrovascular events (OR 4.84 [95 % CI 1.31–17.89], P=0.018), after adjusting for age, sex, BMI, smoking, diabetes duration, hypertension, HbA1c, AER, and eGFR

♦ Results lost significance after adjusting for history of microvascular events

♦ Further analyses revealed that past macrovascular events and BMI were related to incident microvascular events

• eGFR: As skin autofluorescence increased, eGFR significantly decreased (P=0.0001)

♦ Skin autofluorescence was linked to over seven times increased odds of impaired incident eGFR (OR 7.42 [95 % CI 1.59–34.65], P=0.018), after adjusting for age, sex, BMI, smoking, diabetes duration, hypertension, HbA1c, AER, and eGFR

♦ Further analyses revealed arterial hypertension, baseline eGFR <60 ml/min/1.73 m², and skin autofluoresence were related to eGFR <60 ml/min/1.73 m²

• AER: No significant associations with skin autofluorescence (P=0.10)

♦ Further analyses showed that age, initial eGFR <60 ml/min/1.73 m², and initial AER ≥30 mg/24h were associated with final AER ≥30 mg/24 h

Limitations include the inclusion of patients with longstanding T1DM. Participants were treated at a university clinic in which many received renin-angiotensin inhibitors, which precluded the evaluation of earlier events like microalbuminuria. Also, the small size of the study, few incident events during the study, and the percentage of participants lost to follow-up (19%, 243/300) could have further limited the study. Finally, skin AGE levels may be related to tissue turnover, and could be different from AGE levels in the blood.

Despite these limitations, the authors concluded: “The simple, cheap, and quick measurement of skin autofluorescence makes it a good candidate for the screening of patients at risk of diabetic nephropathy.”

Take-home Points

• AGEs may contribute to cardiovascular and renal risk.

• Because AGEs accumulate in the skin, skin autofluroescence may provide an inexpensive, noninvasive way to assess cardio-renal risk in T1DM.

• A small, French study found that macrovascular events and reduced eGFR at four years were significantly associated with higher skin autofluorescence at baseline.

• Past macrovascular events remain the most important factor for predicting future risk

The authors report no conflicts of interest.

References:

1. Vélayoudom-Céphise FL, et al. Skin autofluorescence predicts cardio-renal outcome in type 1 diabetes: a longitudinal study. Cardiovasc Diabetol. 2016 Sep 1;15(1):127.

2. Genevieve M, et al. Skin autofluorescence is associated with past glycaemic control and complications in type 1 diabetes mellitus. Diabetes Metab. 2013 Sep; 39(4):349-354.