Advanced Glycation End Products and Well-Being in Male Subjects with Type 2 Diabetes Mellitus

Letter to the editor

The levels of skin advanced glycation end products (AGEs) are elevated in type 2 diabetes mellitus (T2DM) [1], especially in the presence of diabetic neuropathy [2]. Subjects with T2DM may exhibit reduced well-being, as evaluated by the World Health Organization-5 (WHO-5) questionnaire [3]. This study examined the potential correlation between skin AGEs and well-being index in male subjects with T2DM.

The study included 106 subjects. Their characteristics are summarised in [Table 1]. Inclusion criteria were age>18 years, male gender, and T2DM. Exclusion criteria were age≥85 years, heart failure (New York Heart Association classification 3 and 4), severe illness/infection, hypoglycaemia, liver cirrhosis, dermatologic disease at measuring site, tattoos, exposure to skincare creams/ substance with fluorescent properties/self-tanning agents in the past 10 days, Fitzpatrick skin type>V, chronic kidney disease (estimated glomerular filtration rate<60 mL/min) and psychiatric issues.

Table 1 Participant characteristics.

Parameter
Age (years, mean±SD)	63.5±8.5
T2DM duration (years, mean±SD)	13±9
BMI (kg/m2, mean±SD)	29.9±2.9
HbA1c (%, mean±SD)	7.4±1.1
Antidiabetic therapy (tablets: insulin) (n)	68:38
DPN (n, %)	50 (47.2%)
Retinopathy (n, %)	36 (34%)
CAD (n, %)	21 (19.8%)
Smoking (n, %)	24 (22.6%)
WHO-5 score: DPN vs. no DPN (mean±SD)	15±5.1 vs. 17.9±5.5 (p=0.005)
WHO-5 score: Retinopathy vs. no retinopathy (mean±SD)	10.9±2.8 vs. 18.8±4.1 (p<0.001)

BMI: body-mass index; CAD: coronary artery disease; DPN: diabetic peripheral neuropathy; SD: standard deviation; T2DM: type 2 diabetes mellitus; WHO: World Health Organisation

Skin AGEs were measured with AGE reader mu connect (Diagnoptics, NL) on the dominant arm, as previously reported [2]. Subjects completed the WHO-5 questionnaire [3]. The study was approved by the institutional ethics committee, and participants provided their informed consent. Diabetic peripheral neuropathy (DPN) was defined as diabetic neuropathy score (NDS)≥3 [4]. Diagnosis of coronary artery disease (CAD) and retinopathy was based on medical history.

Overall, 26.4% of participants exhibited low well-being (WHO-5<13). There was a negative correlation between AGEs and WHO-5 score (r=−0.361, p<0.001). This correlation was seen for each of the five questions of WHO-5: r=−0.370, p<0.001 for question 1; r=−0.258, p=0.007 for question 2; r=−0.250, p=0.010 for question 3; r=−0.396, p=0.007 for question 4; r=−0.338, p<0.001 for question 5. WHO-5 score was negatively correlated with T2DM duration (r=−0.239, p=0.014) but not with age. A lower WHO-5 score was seen in the presence of DPN (p=0.005) and retinopathy (p<0.001).

The high frequency of poor well-being in T2DM concurs with two previous works [3] [5] and suggests that increased awareness of this possibility and, perhaps, more widespread use of psychological measures should be considered. This suggestion is in harmony with the increasing concern about mental health in diabetes, especially in the presence of complications [6]. The negative correlation between skin AGEs and well-being is a novel finding and adds to our knowledge on the consequences of increased levels of AGEs. Obviously, this correlation can offer no proof of causation and needs further exploration.

The limitations of this study may be outlined as follows. First, we only included male subjects. Second, we did not include a healthy control group. Third, the study was conducted in a tertiary care center, limiting the generalisabilty of the results. Moreover, we did not use skin biopsy for the measurement of AGEs, but the device employed is an acceptable method [1] [2]. In addition, information on diabetic complications was not complete: CAD and retinopathy were solely based on medical history, while no information on erectile dysfunction was available. Finally, the study provided no prospective data, but this was beyond its scope.

In conclusion, skin AGEs show a negative correlation with well-being in male subjects with T2DM. These results add to our knowledge on the effects of AGEs. Further, especially prospective, data would be welcome to confirm and explore the implications.

Publication History

Article published online:
22 December 2023

• References

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