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Recent studies have demonstrated that the levels of adipocyte fatty acid-binding protein (A-FABP) are closely associated with diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). This study aimed to examine the association between serum A-FABP level and rapid renal function decline in patients with T2DM and preserved renal function.
This was a prospective observational study of 452 patients with T2DM and preserved renal function who had serial measurements of estimated glomerular filtration rate (eGFR). Rapid renal function decline was defined as an eGFR decline of >4% per year. The association between baseline serum A-FABP level and rapid renal function decline was investigated.
Over a median follow-up of 7 years, 82 participants (18.1%) experienced rapid renal function decline. Median A-FABP levels were significantly higher in patients with rapid renal function decline, compared to non-decliners (20.2 ng/mL vs. 17.2 ng/mL,
A high level of serum A-FABP is associated with an increased risk of rapid renal function decline in patients with T2DM and preserved renal function. This suggests that A-FABP could play a role in the progression of DKD in the early stages.
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The aim of this study was to evaluate characteristics and risk of diabetic complications according to age at diagnosis among young adults with type 1 diabetes mellitus (T1DM).
A total of 255 T1DM patients aged less than 40 years were included. Patients were categorized into three groups (<20, 20 to 29, and 30 to 40 years) according to age at diagnosis. Diabetic nephropathy (DN) was defined when spot urine-albumin creatinine ratio was 300 mg/g or more and/or estimated glomerular filtration ratio (eGFR) level was 60 mL/min/1.73 m2 or less.
Median age at diagnosis was 25 years and disease duration was 14 years. Individuals diagnosed with T1DM at childhood/adolescent (age <20 years) had lower stimulated C-peptide levels. They received more intensive insulin treatment with higher total daily insulin doses compared to older onset groups. The prevalence of DN was higher in the childhood/adolescent-onset group than in older onset groups (25.3% vs. 15.3% vs. 9.6%,
In individuals with childhood/adolescent-onset T1DM, the reduction in renal function is more prominent with disease duration. Early age-onset T1DM is an independent risk of DN.
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Fibroblast growth factor 21 (FGF21) has been only reported to prevent type 1 diabetic nephropathy (DN) in the streptozotocin-induced type 1 diabetes mellitus (T1DM) mouse model. However, the FVB (Cg)-Tg (Cryaa-Tag, Ins2-CALM1) 26OVE/PneJ (OVE26) transgenic mouse is a widely recommended mouse model to recapture the most important features of T1DM nephropathy that often occurs in diabetic patients. In addition, most previous studies focused on exploring the preventive effect of FGF21 on the development of DN. However, in clinic, development of therapeutic strategy has much more realistic value compared with preventive strategy since the onset time of DN is difficult to be accurately predicted. Therefore, in the present study OVE26 mice were used to investigate the potential therapeutic effects of FGF21 on DN.
Four-month-old female OVE26 mice were intraperitoneally treated with recombinant FGF21 at a dose of 100 µg/kg/day for 3 months. The diabetic and non-diabetic control mice were treated with phosphate-buffered saline at the same volume. Renal functions, pathological changes, inflammation, apoptosis, oxidative stress and fibrosis were examined in mice of all groups.
The results showed that severe renal dysfunction, morphological changes, inflammation, apoptosis, and fibrosis were observed in OVE26 mice. However, all the renal abnormalities above in OVE26 mice were significantly attenuated by 3-month FGF21 treatment associated with improvement of renal adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) activity and sirtuin 1 (SIRT1) expression.
Therefore, this study demonstrated that FGF21 might exert therapeutic effects on DN through AMPK-SIRT1 pathway.
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Ceramides are associated with metabolic complications including diabetic nephropathy in patients with diabetes. Recent studies have reported that podocytes play a pivotal role in the progression of diabetic nephropathy. Also, mitochondrial dysfunction is known to be an early event in podocyte injury. Thus, we tested the hypothesis that ceramide accumulation in podocytes induces mitochondrial damage through reactive oxygen species (ROS) production in patients with diabetic nephropathy.
We used Otsuka Long Evans Tokushima Fatty (OLETF) rats and high-fat diet (HFD)-fed mice. We fed the animals either a control- or a myriocin-containing diet to evaluate the effects of the ceramide. Also, we assessed the effects of ceramide on intracellular ROS generation and on podocyte autophagy in cultured podocytes.
OLETF rats and HFD-fed mice showed albuminuria, histologic features of diabetic nephropathy, and podocyte injury, whereas myriocin treatment effectively treated these abnormalities. Cultured podocytes exposed to agents predicted to be risk factors (high glucose, high free fatty acid, and angiotensin II in combination [GFA]) showed an increase in ceramide accumulation and ROS generation in podocyte mitochondria. Pretreatment with myriocin reversed GFA-induced mitochondrial ROS generation and prevented cell death. Myriocin-pretreated cells were protected from GFA-induced disruption of mitochondrial integrity.
We showed that mitochondrial ceramide accumulation may result in podocyte damage through ROS production. Therefore, this signaling pathway could become a pharmacological target to abate the development of diabetic kidney disease.
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