Table 1 Human studies investigating the association between skin AGEs and microvascular complications other that diabetic neuropathy
First Author (year) | Participants and diabetes type | Aggregate clinical outcome | Main findings |
|---|---|---|---|
Retinopathy | |||
 Gerrits (2008) [22] | 973 T2DM | Retinal photography | Multivariate analysis (adjustment for sex, diabetes duration, HbA1c, current smoking, systolic blood pressure, HDL cholesterol, LDL cholesterol, triglycerides, BMI): no association |
 Chabroux (2010) [23] | 133 T1DM | Retinal photography | Multivariate analysis (adjustment for age, diabetes duration, HbA1c, smoking, retinopathy, nephropathy and neuropathy): no association |
 Sugisawa (2013) [24] | 210 T1DM/110 controls | Retinal or fundus photography | Multivariate analysis (adjustment for age at registration, age at onset of diabetes, duration of diabetes, sex, BMI, and sAF): positive association with retinopathy; positive association with retinopathy severity |
 Yoshioka (2018) [25] | 162 T2DM/42 controls | Diagnosed by independent ophthalmologists according to a position statement by the American Diabetes Association (no further information in the text) | Multivariate analysis (adjustment for age, diabetes duration, HbA1c, serum pentosidine concentration and eGFR): positive association; positive association with retinopathy severity |
 Bentata (2017) [26] | 444 T2DM (17% with chronic renal insufficiency) | Fundus examination or retinography or (if required) optical coherence tomography | Multivariate analysis (adjustment for age, duration of diabetes, hypertension, insulin, HbA1c and eGFR): no association of sAF and retinopathy among subjects with T2DM and renal insufficiency; positive association among subjects with T2DM and eGFR≥60 ml/min/m2 |
 Tanaka (2012) [27] | 130 T2DM | Retinal photography | Positive association with proliferative diabetic retinopathy but not with simple diabetic retinopathy |
 Yasuda (2015) [28] | 67 T2DM/67 controls | Fundus photography | Association with presence and severity of retinopathy |
 Hirano (2014) [29] | 138 T2DM/111 controls | Ophthalmoscopy and contact lens slit lamp biomicroscopy | Multivariate analysis (adjustment for sex, age, HbA1c, self-stated duration of diabetes, systolic and diastolic blood pressure, history of smoking, diabetic nephropathy, and diabetic neuropathy): association with retinopathy severity; no association with diabetic macular oedema |
 Noordzij (2012) [30] | 563 T2DM | Retinal photography or fundoscopy | Multiple linear regression: no association |
Nephropathy | |||
 Gerrits (2008) [22] | 973 T2DM | Diabetes-associated (micro) albuminuria defined as an ACR > 2.5 mg/mmol for men and > 3.5 mg/mmol for women | Multivariate analysis (adjustment for sex, diabetes duration, HbA1c, current smoking, systolic blood pressure, HDL cholesterol, LDL cholesterol, triglycerides, BMI): positive association |
 Chabroux (2010) [23] | 133 T1DM | Detection of (micro)albuminuria | Multivariate analysis (adjustment for age, diabetes duration, HbA1c, smoking, retinopathy, nephropathy and neuropathy): positive association |
 Sugisawa (2013) [24] | 210 T1DM/110 controls | First method: chronic kidney disease stages 1–5 defined by National Kidney Foundation practice guidelines; second method: 1) normoalbuminuria (ACR < 30 mg/g Cr); 2) incipient nephropathy (ACR ≥30 but < 300 mg/g Cr); 3) overt nephropathy (ACR ≥300 mg/g Cr); 4) chronic renal failure (serum Cr > 2.0 mg/dL); and 5) renal failure on dialysis | Multivariate analysis (adjustment for age at registration, age at onset of diabetes, duration of diabetes, sex, BMI, and sAF): positive association with nephropathy; positive association with severity of nephropathy |
 Yoshioka (2018) [25] | 162 T2DM/42 controls | Classified as: (1) pre-nephropathy (stage 1) (ACR < 30 mg/g Cr); (2) incipient nephropathy (stage 2) (30 ≤ ACR < 300 mg/g Cr); (3) overt nephropathy (stage 3) (ACR ≥ 300 mg/g Cr); (4) kidney failure (stage 4) eGFR < 30 ml/min/1.732; and (5) dialysis therapy (stage 5) | Multivariate analysis (adjustment for age, diabetes duration, HbA1c, serum pentosidine concentration and eGFR): no association; positive association with incipient nephropathy (stage 2) but not with overt nephropathy (stage 3) |
 Rajaobelina (2017) [31] | 154 T1DM | Chronic kidney disease (eGFR < 90 ml/min) and/or albuminuria | Increase of sAF (by at least 10%): linked with deterioration of microalbuminuria and of eGFR |
 Tanaka (2012) [27] | 130 T2DM | Positive dipstick results for proteinuria (≥1 +) | Positive association with proteinuria ≥3.5 g/gCr |
 Noordzij (2012) [30] | 563 T2DM | ACR > 3.5 in women and > 2.5 in men | Multivariate analysis: no association |