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Table 1 Human studies investigating the association between skin AGEs and microvascular complications other that diabetic neuropathy

From: Skin AGEs and 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
  1. ACR Albumin-to-creatinine ratio, BMI body mass index, Cr creatinine, eGFR estimated glomerular filtration rate, HbA1c glycated haemoglobin, HDL high density lipoprotein, LDL low density lipoprotein, SAF skin autofluorescence, T1DM type 1 diabetes mellitus, T2DM type 2 diabetes mellitus