Comparison of Serum Ketone Levels and Cardiometabolic Efficacy of Dapagliflozin versus Sitagliptin among Insulin-Treated Chinese Patients with Type 2 Diabetes Mellitus

Chi-Ho Lee,Mei-Zhen Wu,David Tak-Wai Lui,Darren Shing-Hei Chan,Carol Ho-Yi Fong,Sammy Wing-Ming Shiu,Ying Wong,Alan Chun-Hong Lee,Joanne King-Yan Lam,Yu-Cho Woo,Karen Siu-Ling Lam,Kelvin Kai-Hang Yiu 대한당뇨병학회 2022 Diabetes and Metabolism Journal Vol.46 No.6

Background: Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients.Methods: This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum β-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography.Results: Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e’, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037).Conclusion: Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.

Cellular localization of the full-length isoform of the type 2 corticotropin releasing factor receptor in the postnatal mouse cerebellar cortex

Lee, Kyung-Hoon,Bishop, Georgia A.,Tian, Jin Bin,Jang, Yoon-Jin,Bui, Bao Chi,Nguyen, Truong Le Xuan,Ahn, Jee-Yin,King, James S. Liss 2007 Journal of neuroscience research Vol.85 No.9

<P>Corticotropin releasing factor (CRF) and its cognate receptors, defined as Type 1 and Type 2 have been localized within the cerebellum. The Type 2 CRF receptor (CRF-R2) is known to have both a full length (CRF-R2α) and a truncated (CRF-R2α-tr) isoform. A recent study documented CRF-R2α primarily in Bergann glia and astrocytes, as well as in populations of Purkinje cells in the adult cerebellum. The goal of the present study is to determine if CRF-R2α is present in the postnatal cerebellum, and if so to describe its cellular distribution. RT-PCR data showed that CRF-R2α is expressed in the mouse cerebellum from birth through postnatal day 21. Between birth and P14, CRF-R2α-immunoreactivity was localized within the somata of Purkinje cells, and migrating GABAergic interneurons. GFAP-immunoreactive astrocytes, including Bergmann glia, also expressed CRF-R2α-immunoreactivity from P3-P14. There is a change, however, in CRF-R2α immunolabeling within neurons as the cerebellum matures. Compared to its expression in the adult cerebellum, Purkinje cells, and GABAergic interneurons showed more extensive CRF-R2α immunolabeling during early postnatal development. We postulate that CRF-R2α could be involved in developmental events related to the survival and differentiation of Purkinje cells and GABAergic neurons, whereas in the adult, this isoform of the CRF receptor family is likely involved in modulating Bergmann glia that have been shown to play a role in regulating the synaptic environment around Purkinje neurons. © 2007 Wiley-Liss, Inc.</P>

Improved strut-and-tie method for 2D RC beam-column joints under monotonic loading

Xu Long,Chi King Lee 사단법인 한국계산역학회 2015 Computers and Concrete, An International Journal Vol.15 No.5

In the previous analytical studies on 2D reinforced concrete (RC) beam-column joints, the modified compression field theory (MCFT) and the strut-and-tie method (STM) are usually employed. In this paper, the limitations of these analytical models for RC joint applications are reviewed. Essentially for predictions of RC joint shear behaviour, the MCFT is not applicable, while the STM can only predict the ultimate shear strength. To eliminate these limitations, an improved STM is derived and applied to some commonly encountered 2D joints, viz., interior and exterior joints, subjected to monotonic loading. Compared with the other STMs, the most attracting novelty of the proposed improved STM is that all critical stages of the shear stress-strain relationships for RC joints can be predicted, which cover the stages characterized by concrete cracking, transverse reinforcement yielding and concrete strut crushing. For validation and demonstration of superiority, the shear stress-strain relationships of interior and exterior RC beam-column joints from published experimental studies are employed and compared with the predictions by the proposed improved STM and other widely-used analytical models, such as the MCFT and STM.

A 3D co-rotational beam element for steel and RC framed structures

Xu Long,Kang Hai Tan,Chi King Lee 국제구조공학회 2013 Structural Engineering and Mechanics, An Int'l Jou Vol.48 No.5

A 3-node 3D co-rotational beam element using vectorial rotational variables is employed to consider the geometric nonlinearity in 3D space. To account for shape versatility and reinforced concrete cross-sections, fibre model has been derived and conducted. Numerical integration over the cross-section is performed, considering both normal and shear stresses. In addition, the derivations associated with material nonlinearity are given in terms of elasto-plastic incremental stress-strain relationship for both steel and concrete. Steel reinforcement is treated as elasto-plastic material with Von Mises yield criterion. Compressive concrete behaviour is described by Modified Kent and Park model, while tensile stiffening effect is taken into account as well. Through several numerical examples, it is shown that the proposed 3D co-rotational beam element with fibre model can be used to simulate steel and reinforced concrete framed structures with satisfactory accuracy and efficiency.

A superelement formulation for efficient structural analysis in progressive collapse

Long, Xu,Yuan, Weifeng,Tan, Kang Hai,Lee, Chi King Techno-Press 2013 Structural Engineering and Mechanics, An Int'l Jou Vol.48 No.3

An integrated superelement concept is proposed to improve the computational efficiency when analyzing structural responses during progressive collapses of large-scale structures, such as multi-storey reinforced concrete buildings. While the proposed methodology is straightforward and can be implemented into an existing finite element program with little effort, it is able to significantly reduce the computational cost without the loss of any critical information of the structural responses. Compared with the models without superelement, significant saving in computational cost and satisfactory prediction accuracy can be obtained with the proposed approach.

A 3D co-rotational beam element for steel and RC framed structures

Long, Xu,Tan, Kang Hai,Lee, Chi King Techno-Press 2013 Structural Engineering and Mechanics, An Int'l Jou Vol.48 No.5

A 3-node 3D co-rotational beam element using vectorial rotational variables is employed to consider the geometric nonlinearity in 3D space. To account for shape versatility and reinforced concrete cross-sections, fibre model has been derived and conducted. Numerical integration over the cross-section is performed, considering both normal and shear stresses. In addition, the derivations associated with material nonlinearity are given in terms of elasto-plastic incremental stress-strain relationship for both steel and concrete. Steel reinforcement is treated as elasto-plastic material with Von Mises yield criterion. Compressive concrete behaviour is described by Modified Kent and Park model, while tensile stiffening effect is taken into account as well. Through several numerical examples, it is shown that the proposed 3D co-rotational beam element with fibre model can be used to simulate steel and reinforced concrete framed structures with satisfactory accuracy and efficiency.

A superelement formulation for efficient structural analysis in progressive collapse

Xu Long,Weifeng Yuan,Kang Hai Tan,Chi King Lee 국제구조공학회 2013 Structural Engineering and Mechanics, An Int'l Jou Vol.48 No.3

An integrated superelement concept is proposed to improve the computational efficiency when analyzing structural responses during progressive collapses of large-scale structures, such as multi-storey reinforced concrete buildings. While the proposed methodology is straightforward and can be implemented into an existing finite element program with little effort, it is able to significantly reduce the computational cost without the loss of any critical information of the structural responses. Compared with the models without superelement, significant saving in computational cost and satisfactory prediction accuracy can be obtained with the proposed approach.

Experimental study of welding effect on grade S690Q high strength steel butt joint

Cheng Chen,Sing-Ping Chiew,Mingshan Zhao,Chi King Lee,Tat Ching Fung 국제구조공학회 2021 Steel and Composite Structures, An International J Vol.39 No.4

This study experimentally reveals the influence of welding on grade S690Q high strength steel (HSS) butt joints from both micro and macro levels. Total eight butt joints, taking plate thickness and welding heat input as principal factors, were welded by shielded metal arc welding. In micro level, the microstructure transformations of the coarse grain heat affected zone (CGHAZ), the fine grain heat affected zone (FGHAZ) and the tempering zone occurred during welding were observed under light optical microscopy, and the corresponding mechanical performance of those areas were explored by micro-hardness tests. In macro level, standard tensile tests were conducted to investigate the impacts of welding on tensile behaviour of S690Q HSS butt joints. The test results showed that the main microstructure of S690Q HSS before welding was tempered martensite. After welding, the original microstructure was transformed to granular bainite in the CGHAZ, and to ferrite and cementite in the FGHAZ. For the tempering zone, some temper martensite decomposed to ferrite. The performed micro-hardness tests revealed that an obvious “soft layer” occurred in HAZ, and the HAZ size increased as the heat input increased. However, under the same level of heat input, the HAZ size decreased as the plate thickness increased. Subsequent coupon tensile tests found that all joints eventually failed within the HAZ with reduced tensile strength when compared with the base material. Similar to the size of the HAZ, the reduction of tensile strength increased as the welding heat input increased but decreased as the thickness of the plate increased.