Skin autofluorescence is associated with vascular complications in patients with type 2 diabetes.

AIMS: Tissue accumulatedadvanced glycation end products (AGEs) can be evaluated non-invasively by an autofluorescence reader as skin autofluorescence (skin AF)·The present study investigated whether skin AF is associated with diabetic micro- and macroangiopathies in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: Skin AF was measured in 193 enrolled Japanese patients with T2DM and 24 enrolled healthy non-diabetic subjects by using the AGE reader®. Diabetic micro- and macroangiopathies were evaluated in the T2DM patients. RESULTS: Skin AF was significantly increased in patients with T2DM than in age- and sex-matched non-diabetic controls (2.35 ±â€¯0.51 [mean ±â€¯SD] and 1.91 ±â€¯0.29, respectively, p = 0.001). In subjects with T2DM, skin AF was associated with age, pack-years of smoking, and eGFR (estimated glomerular filtration rate) independently. Skin AF was significantly increased in patients with diabetic retinopathy, neuropathy, nephropathy, and macroangiopathy than in those without them, and significantly associated with the number of diabetic complications. Moreover, skin AF was an independent predictor for diabetic retinopathy, neuropathy, and nephropathy but not macroangiopathy, after adjusting for major traditional risk factors. CONCLUSIONS: Skin AF is an independent predictor for diabetic retinopathy, neuropathy and nephropathy in Japanese patients with T2DM.

Association between Subclinical Atherosclerosis Markers and the Level of Accumulated Advanced Glycation End-Products in the Skin of Patients with Diabetes.

AIM: The level of accumulated advanced glycation end-products (AGEs) in the skin has been shown to predict the risk of complications in patients with diabetes mellitus (DM). Recently, the level of accumulated fluorescent AGEs in the skin has become measurable as skin autofluorescence (skin AF) using a non-invasive apparatus, autofluorescence reader. The purpose of this study was to evaluate the association between skin AF and the subclinical atherosclerosis markers, especially endothelial dysfunction, in patients with DM. METHODS: We enrolled 140 Japanese subjects with DM who attended Osaka University Hospital, and measured the skin level of AGEs by skin AF and three subclinical atherosclerosis markers: endothelial function by flow-mediated vasodilation, FMD; carotid intima-media thickness, IMT; and brachial-ankle pulse wave velocity, baPWV. RESULTS: FMD was significantly associated with skin AF (r=－0.259, p=0.002). Furthermore, a stepwise multivariate regression analysis revealed that skin AF was an independent determinant of FMD (ß=－0.180, p=0.038). Although there were significant associations between skin AF and maximum carotid intima-media thickness (max-IMT)(r=0.298, p＜0.001) as well as baPWV (r=0.284, p= 0.001) in univariate analysis, skin AF was not an independent determinant of either carotid max-IMT or baPWV after adjustment for conventional cardiovascular risk factors. Receiver-operating characteristic curve analysis revealed that skin AF can identify the subjects whose FMD, max-IMT, and baPWV were completely within the normal range (C-statistics, 0.73; 95% confidence interval, 0.61-0.84; p＜0.001). CONCLUSIONS: Skin AF was independently associated with FMD as an indicator of endothelial dysfunction, and can be utilized as a screening marker of atherosclerosis in Japanese patients with DM.

Skin Autofluorescence is Associated with Early-stage Atherosclerosis in Patients with Type 1 Diabetes.

AIM: Accumulation level of fluorescent advanced glycation end products (AGEs) in the skin can be measured non-invasively as skin autofluorescence (skin AF) by autofluorescence reader. The aim of this study was to assess possible associations between skin AF and diabetic complications, especially early-stage atherosclerosis, in Japanese type 1 diabetic patients. METHODS: Skin AF was measured by AGE reader® in 105 Japanese type 1 diabetic patients (34 men and 71 women, aged 37.4±12.4 years (±SD)) and 23 age-matched healthy non-diabetic subjects. Ultrasonic carotid intima-media thickness (IMT), ankle-brachial index (ABI), and brachial ankle pulse wave velocity (baPWV) were evaluated as indices of early-stage diabetic macroangiopathy. Urinary albumin-to-creatinine ratio (UACR), the coefficient of variation of R-R intervals (CVR-R), and presence of retinopathy were also evaluated. RESULTS: Skin AF values were significantly higher in type 1 diabetic patients than in healthy controls (2.07±0.50 (mean±SD) and 1.90±0.26, respectively, p=0.024). Skin AF was associated with carotid IMT (r=0.446, p＜0.001) and baPWV (r=0.450, p＜0.001), but not with ABI (r=－0.019, p=0.8488). Notably, skin AF was an independent risk factor for IMT thickening. Similarly, skin AF was associated with log (UACR) (r=0.194, p=0.049) and was an independent risk factor for UACR. Furthermore, skin AF values were significantly higher in patients with diabetic retinopathy than in those without (2.21±0.08 and 1.97±0.06, respectively, p=0.020). CONCLUSIONS: Skin AF was significantly associated with the presence and/or severity of diabetic complications and was an independent risk factor for carotid atherosclerosis.

Significant elevation of serum dipeptidyl peptidase-4 activity in young-adult type 1 diabetes.

AIMS: Currently, inhibition of dipeptidyl peptidase-4 (DPP-4) is widely used in the treatment of type 2 diabetes. Application of this strategy is awaited as a new therapeutic approach for type 1 diabetes, but the scientific basis is still lacking. This report describes the evaluation of serum DPP-4 activity in type 1 diabetes compared with control subjects, and assessment of relationships between DPP-4 activity and diabetic complication markers and metabolic variables in type 1 diabetes. METHODS: We examined serum DPP-4 activity in Japanese young-adult type 1 diabetes (n=76, females 69.7%, age 30.9 ± 6.2 years, duration of diabetes 16.5 ± 11.1 years; mean ± SD) and healthy controls (n=22). Association of the enzymatic activity with diabetic micro- and macro- vascular complication markers and clinical parameters was also assessed. RESULTS: Subjects with type 1 diabetes displayed significantly higher serum DPP-4 activity than healthy controls (relative value, control: 1.00 ± 0.28, T1D, 1.29 ± 0.38; p=0.0011) independent of other clinical parameters. In type 1 diabetes, DPP-4 activity was positively correlated with duration of diabetes (r=0.248, p=0.031), while not correlated with HbA1c level. In univariate correlation analysis of diabetic complication markers and other metabolic parameters, coefficient of variation of R-R intervals (CVR-R) and gamma (γ)-glutamyltransferase (GGT) levels were correlated with DPP-4 activity. GGT was extracted as an independent variable of DPP-4 activity in multivariate analysis (ß=0.213, p=0.035). CONCLUSIONS: Serum DPP-4 activity is significantly elevated in Japanese type 1 diabetes, suggesting pathophysiological significance of the enzyme in type 1 diabetes.

Aniridia with a heterozygous PAX6 mutation in which the pituitary function was partially impaired.

We herein report the case of a woman with aniridia and with a heterozygous PAX6 mutation. Pax6 is a transcription factor involved in the development of several organs, including the eye, pancreas and pituitary. The patient had been diagnosed with aniridia in childhood and was found to have impaired glucose tolerance with a heterozygous PAX6 mutation 12 years prior to the current admission. Hormone stimulating tests revealed a slightly impaired pituitary function, including subtle hypogonadotropic hypogonadism and borderline growth hormone (GH) deficiency. The present case is the first report of a slightly impaired pituitary function in an aniridia patient with a heterozygous PAX6 mutation.

Juxtaglomerular cell tumor that was preoperatively diagnosed using selective renal venous sampling.

We herein report the case of a patient with a juxtaglomerular cell tumor (JCT). Dynamic enhanced computed tomography revealed a small nodule on the surface of the lower pole of the right kidney. Selective renal venous sampling showed an elevated level of plasma renin activity (PRA) in the right lower pole renal vein only. We performed right partial nephrectomy and diagnosed the patient with JCT. Making a diagnosis of JCT is often difficult due to the small size of the tumor and the lack of lateralization of the PRA on renal venous sampling. This case highlights the importance of performing selective renal venous sampling for the preoperative diagnosis of JCT.