BackgroundTo determine the association between urinary N-acetyl-β-d-glucosaminidase (NAG), a marker of renal tubulopathy, and carotid intima-media thickness (IMT) and plaques in patients with type 2 diabetes mellitus (T2D) and to compare the predictive value of NAG versus albuminuria, a marker of renal glomerulopathy.MethodsA total of 343 participants were enrolled in this retrospective cross-sectional study. We recruited participants with T2D who were tested for blood glucose parameters, urinary NAG, and urinary albumin-to-creatinine ratio (ACR) and had been checked for carotid ultrasonography.ResultsWe classified participants into a below-median urinary NAG group (Group I; n = 172) or an above-median group (Group II; n = 171). Mean, maximum, and mean of maximum carotid IMT and the proportion of patients with carotid plaques were significantly higher in Group II compared with Group I. In multiple linear regression analyses, high urinary NAG (Group II) was significantly associated with carotid IMT, independently of urinary ACR and other confounding factors. In terms of carotid plaques, both urinary NAG and ACR were significantly higher in participants with carotid plaques than in those without carotid plaques. After adjustment for confounding factors, both urinary NAG and ACR were significantly associated with the presence of carotid plaques.ConclusionsElevated urinary NAG, a marker of renal tubular damage, was related to increased carotid IMT and the presence of carotid plaques in patients with T2D. Urinary NAG may be a more sensitive biomarker than urinary albumin for early detection of atherosclerosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0497-7) contains supplementary material, which is available to authorized users.

BackgroundWe investigated the relationship between the glycemic indices glycated albumin (GA) and glycated hemoglobin (HbA1c) and the progression of diabetic vascular complications [diabetic nephropathy (DN) and carotid artery atherosclerosis (CAA)] in subjects with type 1 diabetes (T1D).MethodsA total of 154 participants with a median follow-up of 2.8 years were enrolled in this retrospective longitudinal study. We recruited T1D subjects who had regularly measured urine albumin-creatinine ratios and estimated glomerular filtration rates, as well as tested HbA1c and GA levels consecutively every 3 or 6 months. A subgroup of 54 subjects was measured repeated carotid intima-media thickness (IMT).ResultsWe classified subjects into the DN progression (Group I; n = 30) with either deteriorated stages of chronic kidney disease (n = 18) or albuminuria progression (n = 17), and the non-progression (Group II; n = 124). In multiple logistic regression analyses, baseline albuminuria (odds ratio [OR] = 2.64, 95 % confidence interval [CI] = 1.03–6.74), mean GA levels (OR = 2.03, 95 % CI = 1.27–3.26) were significantly associated with progression of DN. However, there was no association with mean HbA1c (OR = 0.98, 95 % CI = 0.62–1.54). In a subgroup analysis for follow-up measurements of carotid IMT, age was independently associated with the presence of plaque and the mean IMT. However glycemic indices were not significantly associated with CAA.ConclusionsMean GA levels were more closely associated with DN progression than mean HbA1c in subjects with T1D. However, they were not associated with the CAA.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-015-0219-y) contains supplementary material, which is available to authorized users.

Introduction Sodium glucose co-transporter 2 (SGLT2) inhibitors increase urinary glucose excretion (UGE) by reducing the renal threshold for glucose excretion, which results in decreased serum glucose concentrations in patients with type 2 diabetes mellitus (T2D). However, no study to date has determined whether larger increases in UGE after SGLT2 inhibitor treatment correspond to larger reductions in glycated hemoglobin (HbA1C).MethodsWe enrolled participants who were newly prescribed an SGLT2 inhibitor (dapagliflozin 10 mg or ipragliflozin 50 mg, once daily) as an add-on therapy. Patients were tested for HbA1C and first morning spot urinary-creatinine and -glucose concentrations immediately prior to administration of the SGLT2 inhibitor and at a 12-week follow-up appointment. We investigated the relationship between increases in morning spot UGE and decreases in HbA1C.ResultsA total of 101 participants with T2D were enrolled. The median age and diabetes duration were 61.0 and 12.8 years, respectively, and the median HbA1C was 8.10%. SGLT2 inhibitors significantly lowered the HbA1C level, with a median change from baseline to week 12 of −0.60% (p < 0.001). Robust increases from baseline were seen for the morning spot urinary glucose-to-creatinine ratio (UGCR), with a median change at week 12 of 47.3 mg/mg. In the correlation analysis, the ∆HbA1C level showed a significant positive correlation with ∆morning spot UGCR (r = 0.395, p < 0.001). In other words, a greater reduction in HbA1C was correlated with a smaller increase in UGE. After adjusting for confounding variables, ∆HbA1C was significantly associated with ∆morning spot UGCR.ConclusionsAlthough SGLT2 inhibitor treatment leads to a reduced HbA1C level by augmenting UGE, larger increases in UGE do not correlate to larger reductions in HbA1C. This suggests that the increase in UGE might not be an indicator of the degree of reductions in blood glucose.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0248-5) contains supplementary material, which is available to authorized users.