OBJECTIVE -Current criteria for the diagnosis of diabetic ketoacidosis (DKA) are limited by their nonspecificity (serum bicarbonate [HCO 3 ] and pH) and qualitative nature (the presence of ketonemia/ketonuria). The present study was undertaken to determine whether quantitative measurement of a ketone body anion could be used to diagnose DKA. RESEARCH DESIGN AND METHODS-A retrospective review of records from hospitalized diabetic patients was undertaken to determine the concentration of serum -hydroxybutyrate (OHB) that corresponds to a HCO 3 level of 18 mEq/l, the threshold value for diagnosis in recently published consensus criteria. Simultaneous admission OHB and HCO 3 values were recorded from 466 encounters, 129 in children and 337 in adults. RESULTS -A HCO 3 level of 18 mEq/l corresponded with OHB levels of 3.0 and 3.8 mmol/l in children and adults, respectively. With the use of these threshold OHB values to define DKA, there was substantial discordance (ϳՆ20%) between OHB and conventional diagnostic criteria using HCO 3 , pH, and glucose. In patients with DKA, there was no correlation between HCO 3 and glucose levels on admission and a significant but weak correlation between OHB and glucose levels (P Ͻ 0.001).CONCLUSIONS -Where available, serum OHB levels Ն3.0 and Ն3.8 mmol/l in children and adults, respectively, in the presence of uncontrolled diabetes can be used to diagnose DKA and may be superior to the serum HCO 3 level for that purpose. The marked variability in the relationship between OHB and HCO 3 is probably due to the presence of other acid-base disturbances, especially hyperchloremic, nonanion gap acidosis. Diabetes Care 31:643-647, 2008R ecently published consensus criteria for diagnosing diabetic ketoacidosis (DKA) include a serum bicarbonate (HCO 3 ) level Յ18 mEq/l, pH Յ7.30, the presence of ketonuria/ ketonemia, an anion gap Ͼ10 mEq/l, and a plasma glucose concentration Ͼ250 mg/dl (13.9 mmol/l) (1). The development of a consensus statement represents an advance in view of the divergence of opinion that has existed concerning what the standards for diagnosis of DKA should be (2). However, these diagnostic criteria have limitations. Anion gap, HCO 3 , and pH are relatively nonspecific for DKA because they can be affected by the degree of respiratory compensation or the presence of a separate acid-base disturbance. Ketonuria and ketonemia are usually determined with the nitroprusside assay, which detects acetoacetate (AcAc) but not the most abundant ketone body, -hydroxybutyrate (OHB) (3). Moreover, the measurement is not quantitative (4).Ketone body anion concentrations (i.e., AcAc and OHB), on the other hand, directly reflect the rate of ketone body production (5), which is accompanied by equimolar production of hydrogen ions (6). The present study was undertaken to investigate how a laboratory-based measurement of serum OHB might be used as part of simplified diagnostic criteria for the diagnosis of DKA. RESEARCH DESIGN AND METHODS -We retrieved electronic medical records da...
Type 2 diabetes (T2D) is characterized by insulin resistance along with pancreatic β cell failure. β cell factors are traditionally thought to control glucose homeostasis by modulating insulin levels, not insulin sensitivity. Exosomes are emerging as new regulators of intercellular communication. However, the role of β-cell-derived exosomes in metabolic homeostasis is poorly understood. Here, we report that microRNA-26a (miR-26a) in β cells not only modulates insulin secretion and β cell replication in an autocrine manner but also regulates peripheral insulin sensitivity in a paracrine manner through circulating exosomes. MiR-26a is reduced in serum exosomes of overweight humans and is inversely correlated with clinical features of T2D. Moreover, miR-26a is down-regulated in serum exosomes and islets of obese mice. Using miR-26a knockin and knockout mouse models, we showed that miR-26a in β cells alleviates obesity-induced insulin resistance and hyperinsulinemia. Mechanistically, miR-26a in β cells enhances peripheral insulin sensitivity via exosomes. Meanwhile, miR-26a prevents hyperinsulinemia through targeting several critical regulators of insulin secretion and β cell proliferation. These findings provide a new paradigm for the far-reaching systemic functions of β cells and offer opportunities for the treatment of T2D.
Acyl Activating Enzyme3 (AAE3) was identified to be involved in the catabolism of oxalate, which is critical for seed development and defense against fungal pathogens. However, the role of AAE3 protein in abiotic stress responses is unknown. Here, we investigated the role of rice bean (Vigna umbellata) VuAAE3 in Al tolerance. Recombinant VuAAE3 protein has specific activity against oxalate, with K m = 121 6 8.2 mM and V max of 7.7 6 0.88 mmol min 21 mg 21 protein, indicating it functions as an oxalyl-CoA synthetase. VuAAE3-GFP localization suggested that this enzyme is a soluble protein with no specific subcellular localization. Quantitative reverse transcription-PCR and VuAAE3 promoter-GUS reporter analysis showed that the expression induction of VuAAE3 is mainly confined to rice bean root tips. Accumulation of oxalate was induced rapidly by Al stress in rice bean root tips, and exogenous application of oxalate resulted in the inhibition of root elongation and VuAAE3 expression induction, suggesting that oxalate accumulation is involved in Al-induced root growth inhibition. Furthermore, overexpression of VuAAE3 in tobacco (Nicotiana tabacum) resulted in the increase of Al tolerance, which was associated with the decrease of oxalate accumulation. In addition, NtMATE and NtALS3 expression showed no difference between transgenic lines and wildtype plants. Taken together, our results suggest that VuAAE3-dependent turnover of oxalate plays a critical role in Al tolerance mechanisms.
To compare the efficiency, efficacy, and safety, as well as the educational value, of heads-up (three-dimensional visualization system-assisted) and traditional microscopic cataract surgery.Methods: This randomized noninferiority trial enrolled 242 eyes of 201 patients who received femtosecond laser-assisted cataract surgery. The questionnaire study enrolled 26 medical interns and 39 medical students. Patients received surgery under either a three-dimensional visualization system (3D group, 117 eyes) or traditional microscope (TM group, 125 eyes) after random allocation. The primary outcome was surgical time. The noninferiority margin of surgical time was 60 seconds. Secondary outcomes included ultrasound power, phacoemulsification time, visual acuity, intraocular pressure, endothelial cell density, central corneal thickness, complications, and observer satisfaction scores for surgical procedures.Results: Surgical time was 462.03 ± 80.36 seconds in the 3D group and 452.13 ± 76.63 seconds in the TM group (difference 9.90 seconds; 95% CI, -9.98 to 29.78; P = 0.365). Visual acuity and other perioperative parameters were comparable between the 3D group and the TM group (all P > 0.05). Incidences of both intraoperative and postoperative complications were low and not statistically different between groups (all P > 0.05). Across all observers, 3D surgery was superior to TM surgery for improving the degree of satisfaction (all P < 0.001). Conclusions:The surgical efficiency of heads-up cataract surgery is not inferior to traditional microscopic surgery. Both methods achieved similar efficacy and safety outcomes. Moreover, heads-up cataract surgery showed a significant advantage in medical education.Translational Relevance: Our findings show that heads-up cataract surgery has comparable efficiency, efficacy, and safety, as well as superior medical educational value, to TM surgery, which lays the foundation for promoting and popularizing this technology.
Formate dehydrogenase (FDH) is involved in various higher plant abiotic stress responses. Here, we investigated the role of rice bean (Vigna umbellata) VuFDH in Al and low pH (H + ) tolerance. Screening of various potential substrates for the VuFDH protein demonstrated that it functions as a formate dehydrogenase. Quantitative reverse transcription-PCR and histochemical analysis showed that the expression of VuFDH is induced in rice bean root tips by Al or H + stresses. Fluorescence microscopic observation of VuFDH-GFP in transgenic Arabidopsis plants indicated that VuFDH is localized in the mitochondria. Accumulation of formate is induced by Al and H + stress in rice bean root tips, and exogenous application of formate increases internal formate content that results in the inhibition of root elongation and induction of VuFDH expression, suggesting that formate accumulation is involved in both H + -and Al-induced root growth inhibition. Over-expression of VuFDH in tobacco (Nicotiana tabacum) results in decreased sensitivity to Al and H + stress due to less production of formate in the transgenic tobacco lines under Al and H + stresses. Moreover, NtMATE and NtALS3 expression showed no changes versus wild type in these over-expression lines, suggesting that herein known Al-resistant mechanisms are not involved. Thus, the increased Al tolerance of VuFDH over-expression lines is likely attributable to their decreased Al-induced formate production. Taken together, our findings advance understanding of higher plant Al toxicity mechanisms, and suggest a possible new route toward the improvement of plant performance in acidic soils, where Al toxicity and H + stress coexist.
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