\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"}]},book:{item:{type:"book",id:"9963",leadTitle:null,fullTitle:"Advances and Applications in Deep Learning",title:"Advances and Applications in Deep Learning",subtitle:null,reviewType:"peer-reviewed",abstract:"Artificial Intelligence (AI) has attracted the attention of researchers and users alike and is taking an increasingly crucial role in our modern society. 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He is a full-time researcher at the Laboratory of Neuropharmacology, Institute of Neuroethology, Universidad Veracruzana. He is a lecturer in Neuropsychopharmacology and belongs to the National System of Investigators (SNI 2) and Mexican Academy of Sciences. His research interests include the effects of neurosteroids and natural products on anxiety, depression, and neuronal activity in some brain structures related to anxiety and depression disorders. He has published multiple specialized scientific papers, book chapters, and books. 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He is currently a researcher at the Institute of Health Sciences, Universidad Veracruzana and a member of the National System of Investigators (SNI I). His research interests include experimental models of anxiety and depression, neurobiology of behavior, particularly addiction and food intake as a reward with a translational perspective. He has published 10 book chapters and 13 scientific papers and made more than 20 presentations at international conferences. He has also published several works of science divulgation. 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In the conditions of modern construction, the reduction of material consumption with simultaneous increase in reliability and ensuring favorable indicators of economic efficiency is one of the priorities of designers. The main of the many ways to improve the efficiency of construction is the development and improvement of new progressive lightweight structural forms, which significantly improve the technical and economic performance. Recently, a large popularization received various combined systems, which include elements of different stress-strain state. Research of new constructive forms with application of progressive technologies and materials, new algorithms of calculation by numerical methods opened ways of wide distribution of the combined systems abroad. Robot welding line gave the possibility of making resource-saving structures with corrugated walls (beams, columns, arches) and complex light metal structures made of profile pipes an alternative to traditional constructive solution. A comprehensive solution to this problem requires the development of new resource-efficient designs. With the aim of developing constructive solutions resource consuming structures presents a series resource consuming constructive solutions. The use of such solutions leads to a significant reduction in material consumption with sufficient performance indicators. The light beams can be used in truss structures of beam cages and other beam structures in the construction of residential and public buildings, attics, superstructures, hangars and extensions.
Theoretical and experimental studies of steel beams with corrugated walls are presented in scientific papers [1, 2, 3]. In [1] it is noted that in recent years light profiled steel beams (CWSBs) are gaining increasing popularity. The bearing capacity of such structures is lower than the beams with a flat wall and trusses. The existence of three types of failures, namely local, General and mixed, is determined on the basis of experimental studies. Let us consider in detail the results of nonlinear finite element analysis. It is revealed that the shear stress is at the maximum and the same throughout the wall until swelling. Also experimental beams had a margin of carrying capacity, about half of the limit. In the course of the analysis it is proved that the shear stress is the same throughout the low-profile wall and has a maximum value. The authors confirmed the feasibility of using 1993-1-5 for beams with corrugated wall. In [2] the authors consider the theory of stocky beams and propose a new method of nodal lines. This method applies to thin-walled or thick-walled stocky beams. The paper presents the results of solving the problem of delay shift box girder of different thickness. Also, the values of the normal stress of the box beam due to the restrained torsion are obtained. As a result of the research, the authors obtained the values of shear stresses of the box beam due to shear forces. The results of mathematical modeling of transverse shear effect for sandwich beams with sinusoidal corrugated cores are presented in [3]. The authors studied the bending and bending of two sandwich beams, identified trends and the main problem points, presented theoretical models. The possibilities of influence of transverse shear effect on deflections and critical loads of such structures are shown. The results were confirmed by numerical analysis. The main advantages of truss structures are presented. The author’s approaches to the variability of use and layout of farms are presented in [4]. In [5] the authors investigate tabular structures. The article calculates the optimal size of the welded tubular truss, analyzes the structural constraints, especially on the strength, stress elements, and geometric parameters of the nodes of the trusses. This optimization makes it possible to notice that the optimal height is determined by a geometric restriction that prescribes the minimum angle of inclination of the diagonals. The authors have calculated the cost parameters of such structures. After comparing the costs of a reinforced pipe and a larger pipe, it was found that the cost of the first is much lower. In work [6] it is noted that in the conditions of modern construction the metal frame becomes gaining popularity and has an esthetic appearance, safe connections, an opportunity to reduce sections of elements, belongs to fast-built designs. The authors highlighted the advantages and disadvantages of aluminum and steel, the analysis of the cost of these materials. Patent developments closest on design features are presented in [7, 8, 9]. In [7] represented Beam I-section with a corrugated wall comprising a shelf and welded to them a wall of corrugated metal sheet with a transverse arrangement of corrugations of arbitrary shape, characterized in that the wall consists of two or more parallel connected corrugated sheets, and the shelves are made of steel-concrete, consisting of rigid reinforcement in the form of corrugated sheet metal and reinforcement cage, including longitudinal reinforcement and transverse reinforcement, which embraces the longitudinal reinforcement, connected to it, its ends with a bend inside are welded to a corrugated sheet of metal with a space from the beam wall. In [8] the authors developed a metal beam with a corrugated wall comprising a belt connected to each other by a corrugated wall with a transverse arrangement of the corrugations by welding, characterized in that it is provided with angles arranged in pairs in the center of the belts parallel to their longitudinal axes, with the outer surfaces of the shelves of the corners are rotated to each other and welded straight weld with a gap between the shelves sufficient to install the corrugated wall, which is fixed by means of an adhesive composition. The beam with a corrugated asymmetric profile wall [9] contains a compressed and stretched belt and wall. The wall, at least in some areas, is traditionally or variably corrugated with transverse corrugations. The profile of the corrugations is asymmetric with respect to the plane passing through the top of the corrugation and normal to the longitudinal axis.
In General, this section is aimed at presenting improved structural forms of resource—economic beams, arches, trusses, the introduction of which will give a significant economic effect, high characteristics of bearing capacity and architectural expressiveness, minimize material and labor costs and provide the possibility of using modern technological equipment of the European level, a wide range of applications in construction, esthetics and many other advantages.
The proposed beams with cross-profiled wall of trapezoidal (sinusoidal) shape with belts of channels on self-tapping screws are shown in Figure 1. The structure of such structures includes a single profiled wall (1), trapezoidal (sinusoidal) shape, which is fixed by screws (4) belt (2) (bent or rolled channels). With the help of welding (3) support ribs (5) (welded brands) are adjacent to the belts, and the wall is attached by means of a lamella screws (4). The proposed design of a steel beam with a cross-profiled box-section wall with uneven pitch of corrugations is shown in Figure 2. The profiled wall (2) of the beam has a trapezoidal shape, consists of long (4) and short (3) horizontal sections of the profiled sheet, as well as an inclined section of the corrugation (5). The corrugations of the presented beam have uneven steps that can be adjusted, which is not possible for wavy walls.
Beam with cross-profiled wall with belts of channels on self-tapping screws: (a) trapezoidal wall [10]; (b) sinusoidal wall [11].
Beam with a cross-profiled box-section wall with uneven pitch of corrugations [12].
The wall of the beam is two cold-formed profiled sheets (2), fixed to the belts and ribs (6) around the perimeter, or in this case using lamellas (8), by welding (7). The beam ends have support ribs (6) and the I-beam shelves (1) are made of sheets. The main feature of the work is that the action of the bending moment is perceived by the shelves, and the transverse force is the wall of the beam.
Represented a modified form suggested above I-beam, steel beam from a transversely profiled wall of the box section with unevenly-spaced corrugations and intermittent welds (Figure 3). The structure of such a beam includes a trapezoidal profiled wall (2), which is welded on both sides intermittently (6) only on horizontal sections (3, 4) parallel to the longitudinal axis of the beam. The wall of the beam consists of two profiled sheets, which are attached to the edges (5) by continuous welding, and to the belts (1) by means of broken welds, which distinguishes it from the previous one, while providing savings in weld metal. The peculiarity of the beam is that the sections of corrugations are not transmitted longitudinal deformation, which provides a more uniform loading of the beam wall from the shelves.
Beam with cross-profiled box-section wall with intermittent welds [13].
Intermittent welds provide a uniform redistribution of forces in the shelves on the wall of the beam, as in the continuous seams forces quickly fall to a minimum. This occurs without action in the operation of most of the wall. In this case, intermittent welds (length of individual sections from 50 to 150 mm, and the distance between the sections, usually 1.5–2.5 times the length of the site) give some savings in production costs and provide sufficient stability of the wall, which does not perceive the efforts of the beam plane.
New designs of steel beams with cross-profiled box-section wall with welded-brand belts are proposed (Figure 4) and with the t-belt from rolling- (Figure 5). The profiled wall (2) of the beam has a trapezoidal shape, which is formed from the inclined section of the corrugation (7), long (4) and short (3) horizontal sections of the profiled sheet. The wall of the beam consists of two profiled sheets (2), fixed by spot welding (6) belt (1), which consist of welded or rolled brands parallel to the axis of the beam. The wall in the support ribs (5) is attached by continuous welding (8). In this case, spot welds are used to attach the t-belts and the wall, which leads to the elimination of complex stress state. Attachment of the wall sections, which are close to the belt by spot welding, gives some flexibility to the wall along the beam and provides rigidity of the beam as a whole, as well as reversible perception of local stresses in the beam wall.
Beam with cross-profiled box-section wall with welded-brand belts [14].
Beam with cross-profiled box-section wall with the t-belt from rolling [15].
The wall does not reach the shelf and does not perceive normal forces, but only transverse force (shear stresses). The normal stresses are perceived only t-belts, as in an ideal I-beam. On the support parts of the beam, composite welded t-bar support ribs are used, which provide stability. The main advantage of such structures is that the belts from the brands perceive the action of the bending moment in the beam and work on tension and compression as an ideal I-beam, and the wall perceives the transverse force. In the areas of connection of the wall and shelves in the form of brands there is no zonal normal stresses in the upper and lower parts of the wall. In addition, the installation of t-bearing ribs provides stability and elimination of wall buckling in the area of the support unit. The wall of the rolling brand has a significant height, which ensures the strength of the belt and the upper part of the beam wall at normal stresses. The change in normal stresses is indicated by a hyperbolic dependence, which has maximum values at the top of the wall. Small local loads on the upper beam belt are more evenly distributed on the beam wall due to the t-belt.
A steel beam with profiled box-section wall with polystyrene foam is shown in Figure 6.
Beam with profiled box-section wall with polystyrene foam [16]: (a) initial blank; (b) ready compartment.
This construction (Figure 6) consists of profiled sheets (walls)(7) and support ribs (3). The space between them is filled with polystyrene foam (5). Belts (1) and guides (4) are made of square tubes, which are attached by solid welding. The wall is attached to the guides with self-tapping screws (2). The production of the beam begins with welding the initial billet. The wall of the beam is performed first by installing the profile on one side of the beam. In the future, the beam is in a horizontal position, where the polystyrene is applied in layers with subsequent installation of the upper profiled sheets.
The attachment of the profiled sheets is performed by self-tapping screws and installation through the mounting guides to prevent wall buckling. This course provides the opportunity to use a profiled wall of a smaller thickness (galvanized sheets), which is impossible or very difficult to weld. The sheets are joined together and fixed with screws. The use of polystyrene filling allows the use of this design with high thermal protection and sound insulation characteristics.
A new form is a beam with cross-profiled box-section wall and with belts of bent channels (fastening on screws) (Figure 7). This design allows the use of thin belts profiled sheets from 1 to 2 mm (welding is difficult). The structure of this design includes a profiled wall (1), which has a trapezoidal shape and consists of two profiled sheets, which are fixed to the belts (2) in the form of bent or rolled channels with screws (4). Profiles can be fastened together with self-tapping screws. The support ribs (5) are welded marks that are attached to the belts by welding (3) and to the wall by screws (4). The wall of this design can be single and have a wavy outline.
Beam with cross-profiled box-section wall with belts of bent channels [17].
Below are steel beams with transversely profiled box-section wall, unfastened by diagonal lattice (Figure 8) and cross lattice (Figure 9), lattice in the form of arch elements (Figure 10).
Beam with transversely profiled box-section wall, unfastened by diagonal lattice [18]: (a) initial blank; (b) ready compartment.
Beam with transversely profiled box-section wall, unfastened by cross lattice [19]: (a) initial blank; (b) ready compartment.
Beam with transversely profiled box-section wall, unfastened by lattice in the form of arch elements: (a) initial blank with double arched elements; (b) ready compartment with double arched elements [20]; (c) ready compartment with one arched element [21].
In these structures, the profiled wall (7) of the beams is trapezoidal and consists of two profiled sheets, which are fixed in the guides (4) in the form of square pipes with self-tapping screws (2). The guides are attached to the belts (1), which consist of square tubes, by means of continuous welding (6). The support ribs (8) are made of sheets taking into account the work of crushing and cutting. The grate (3) is attached to the profiled sheets by self-tapping screws (2). Holes can be made to attach beams to a possible column (5).
Initial blanks for this type of structures, as well as for the following are performed at the beginning of the manufacture of beams. The location of the diagonal of the lattice must match the local load on the top chord of the beam. If you are installing a diagonal lattice, you can avoid using stiffeners under local load. Another feature of this type of construction is that the elements of the lattice in combination with the profiled wall provide greater stability than the individual struts of the lattice and the wall. Considering the cross lattice (Figure 9), it is possible to note its superiority in rigidity of a wall and ensuring stability of a wall on all height of a beam. Cross grid distributes the action of bending moment along the length of the span and unfastened profiled sheet to ensure sustainability.
Lattice of arched elements (Figure 10) and their shape reproduce the plot points and take some of the action. In areas close to the supports, the arches intersect and perceive additional forces in the zone of inclined cross-sections of the beam. In the span, the cross-section of the I-beam is close to the “ideal I-beam”, which is the optimal cross-section for the perception of bending moment. In order to obtain less metal-nitrate structures, it is rational to use an arched lattice, which can be both double and single.
The calculation of combined beams from sheet or tubular belts is performed on a PC using a full-dimensional continuous description in the calculation complexes or on models with a breakdown into separate systems taking into account the physical and geometric nonlinearity. The use of the presented structures is not limited to truss structures, but extends to floor beams, crossbars of single—and multistory buildings, arches, galleries, technological platforms, span structures of bridges and the like. There is a possibility of application of the presented designs in beam systems with static loading.
The use of this type of beams provides a number of advantages in comparison with conventional ones, namely esthetic appearance, strength and reliability, durability of structures, low operating costs, but their main advantage is ease and stability.
One of the ways to improve light load-bearing structures, in our opinion, is the use of structural elements of closed profiles, which can have different sections, in particular square, rectangular and oval. Considering the technological features of manufacturing, we note that the pipe section is primarily round, and eventually deformed by various methods (hot and cold), acquiring different shapes.
New design solutions of combined resource-efficient metal structures of trusses and arches are proposed (Figures 11–14). In particular, Figure 11 shows the combined metal structure of the truss with belts in the form of rectangular pipes, the lower belt in the form of a curved down arch that works on tension. This lower belt design is more economical than compressed belt. The upper belt in the form of two compressed rectangular pipes and unfastened by Breweries works as a whole system and can perform additional functions of fencing. This design feature provides an opportunity to reduce the material consumption and generally improve the efficiency of the whole structure.
Truss combined metal structure [22].
Resource-saving combined metal structure (length from 8 to 30 m) [23].
Combined structure of a metal arch with racks [24].
Combined structure of metal trusses with upper spatial zone [25].
So, the composition of the proposed combined metal truss structure include (Figure 11): (1, 3) to the upper belt in the form of two rectangular pipes (section pipe size from 120 to 200 mm); (2) the lower zone of the rectangular pipes in the form of an arched element (section pipe size from 120 to 200 mm); (4, 5) bearing edges of the continuous sheet (thickness from 6 to 10 mm); (6) reference sheet (thickness from 10 to 20 mm); (7) retaining wall (thickness from 8 to 12 mm); (8) lattice (section pipe size from 80 to 100 mm); (9) element of the lattice of the upper belt and at the same time enclosing structure (half arches, section pipe size from 40 to 60 mm).
The combined metal structure of the truss is proposed due to the paired upper arched belt and the lower belt, which works on tension, provides multivariance of application and significantly reduces material costs. The load from the coating in the form of transverse beams (beam cage) is transmitted to the lower part of the upper belt, which is unfastened from the plane of the farm and works with the flooring as a spatial system. The upper part of the upper belt, if necessary, can be unfastened from the plane by triangular dual-purpose supports for communications (pipelines, etc.). The rational use of the proposed structures for spans of 24–36 m is recommended.
The development of combined structures in the form of trusses can occur through the use of spatial triangular rod elements for the upper belt, which will increase the stability of the truss plane and reduce the cost of the structure by weight compared to solid sections. Note that the complexity of such structures is growing, so you need to evaluate these projects at the given cost.
Considering the traditional forms of arched structures, we note that their solid elements work as compressed curved and additionally perceive transverse forces. For this type of compressed curved arches optimal design solution is considered to be I-section with a solid wall. In our opinion, the use of corrugated walls in the arches of the composite I-section is quite controversial, since the corrugated wall perceives the transverse force, and for the perception of the longitudinal force there is a constructive need for the use of additional elements, for example, cross lattice. Such a constructive move increases the cost of arches, increases the metal consumption and the complexity of manufacturing such types of structures. Consequently, the use of continuous wall corrugation, both in arches and columns will not provide the necessary technical and economic effect and as a result, is not very rational.
If we consider the design of the truss, the lower belt which works as a stretched curved element, and the upper belt works on compression (for the case without a wall—Central compression, and in General, off-center compression), it is possible to use in these structures corrugated wall, which would perceive the transverse load. For this type of construction, the stiffness of the corrugated wall in the longitudinal direction will be minimal, however, these efforts will only perceive the belt, and a significant proportion of the transverse forces will be perceived corrugated wall compatible with the belts. Corrugated wall also loosens the belt in the plane of the structure.
The combined structure with the upper and lower belts in the form of square pipes is presented. The latter works as an arched element (Figure 12): (1) the upper belt of rectangular pipes (section pipe size from 120 to 200 mm); (2) the lower belt of rectangular pipes in the form of an arched element; (3) ribs (thickness from 6 to 8 mm); (4) the wall of a single sheet (thickness from 6 to 8 mm); (5) corrugated wall wavy shape (possible thickness from 2 to 3 mm); (6) support sheet (thickness from 8 to 10 mm); (7) support edge (thickness from 10 to 12 mm); (8) angular welding (thickness from 4 to 6 mm).
There is a possibility of performing the supporting sections of such structural solutions with the use of steel sheets, which will provide greater bearing capacity under the action of transverse forces. In turn, the corrugation must be performed in the span areas. It should be noted that under the condition of perception of local concentrated loads by the design, there is a need to install stiffeners both in traditional composite beams and in the above structures, since they perform the functions of ensuring the stability of the wall. The combined design is shown (Figure 12) are an alternative to conventional beams and trusses, which provides a reduction in the construction height (can simultaneously perform the function of the enclosing structure), transport and installation costs.
The combined structure of metal trusses with upper spatial zone is presented (Figure 13). This design solution can be used as a single-arched system, reinforced with a system of racks with optimal performance, in particular, with an optimal ratio of height and span of the supporting structure. The design feature of this type of structures is the use of elements in the form of rectangular pipes and cantilever arch support system.
The main elements of the presented design are: (1) the main element of the arch-a rectangular pipe (section pipe size from 120 to 200 mm); (2) the upper belt of a rectangular pipe (section pipe size from 120 to 200 mm); (3) the lower belt of a rectangular pipe (section pipe size from 80 to 100 mm); (4, 5, 6) racks (section pipe size from 80 to 100 mm); (7) the base plate of the sheet (thickness from 6 to 10 mm); (8) the support edge of the sheet (thickness from 10 to 20 mm). Considering the technological advantages of such a structural form, we note that it is possible to use reduced corrosion-resistant sections of the optimal shape (rectangular pipes) to obtain resource-economic structures with a minimum weight. Outlining the stages of manufacturing this welded arch with racks, a necessary step is to secure the installation with bolts of high strength. The authors recommended the rational use of combined structures of metal arches with racks for spans 12–36 m.
With the aim of obtaining optimal performance constructive solutions have been proposed combined structure metal truss with upper spatial zone (Figure 14): (1) runs; (2) ties; (3) longitudinal edge of a solid sheet (thickness from 8 to 12 mm); (7, 10) branches of the upper belt in the form of three round (rectangular) pipes (section pipe size from 80 to 100 mm); (4, 11) transverse support ribs of a solid sheet (thickness from 6 to 10 mm); (5) support sheet (thickness from 10 to 20 mm); (6) lattice element; (9) struts of the through belt of the truss (section pipe size from 80 to 100 mm); (8) element of the truss lattice (section pipe size from 100 to 160 mm).
This design form can be used in light load-bearing coating structures with profiled steel flooring. For this type of structures span can vary from small (24 m) to significantly large (more than 36 m). The recommended slope designs may be a standard 1.5%, and a large (as per design assignment). It is possible to use the arched shape of the truss for the corresponding spans. For this type of structures, the height of the truss is determined by the stiffness and depends on the span. Considering the design features of the combined structure of the truss with a spatial upper belt, it should be noted that the installation parts of the farms are performed according to the standards for the transportation of goods. It is recommended to connect the mounting elements of the trusses with flanges on bolts, as well as by welding, using pipes of larger diameter, which significantly reduces the metal content of the connections. Runs between truss are made of rolling profiles and fixed according to the continuous scheme, due to the wide upper belt of the farm. It should be noted that the use of this type of structures is due to economic calculations according to the above costs compared to standard coating structures.
The increase in the complexity of the manufacture of spatial structures is overlapped by a decrease in the material intensity of structures, which makes it possible to obtain more economical designs. The proposed new constructive solutions of steel space trusses, arches and frames which have the characteristics of high bearing capacity and the architectural expression, to minimize the indicators of material and labor costs. Structures of this type have increased characteristics of the overall stability of the individual elements and the system as a whole both in the plane and from the plane. As a result of the study, a number of design solutions of light combined structures are presented, which have a wide range of applications in construction. The advantages of the proposed solutions are ease, industry and great rigidity. Numerical calculations of frame structures allowed to bring the efficiency of these design solutions and track a significant reduction in effort in the racks.
Type 2 diabetes mellitus (T2D) is a syndrome of disturbed metabolic pathways of sacharides (carbohydrates), proteins and fat due to various influence of eight pathophysiologic mechanisms described as ominous octet: disturbed dynamics of insulin secretion, reduced production of incretins in gut, hyperglucagonaemia, increased production of glucose from liver, disturbed endocrine function of adipose tissue, insulin resistance, increased activity of sodium glucose transporter 2 (SGLT2) resulting in increased reabsorption of glucose from renal tubules and malfunction of hypothalamic centers for satiety and hunger. [1] These mechanisms are induced by different genetic and environmental factors. [2, 3]
In previous centuries, clinical symptoms of T2D lead to therapeutic attempts based on lifestyle, diet and on oral antidiabetic drugs, mostly sulfonylureas.
The discovery of insulin by Paulesco in 1921 [4] and its final introduction to human medicine by Banting, Collip, Best and Macleod in 1922 [5] saved many lives of people with T1D. However, in T2D insulin was mostly used as an ultimate therapeutic alternative.
In 1957, the discovery of metformin resulted in reduction of hyperglycaemia without hypoglycaemias. In the course of several decades, metformin proved to be a relatively effective mean to reduce body mass and cardiovascular complications. In addition, in persons on metformin the frequency of neoplasms appears to be lower. Today, metformin undoubtedly remains the drug worthy of choice for the majority persons with T2D. [6]
At the end of the 20th century, a new concept of pathophysiologic approach to T2D was suggested by Bruns [7] under the descriptive term „complementary therapy“, and, independently by Berger [8, 9] as „supplementary therapy“.
Important role in the intensification of insulin regimens played insulin pens which were produced since the year 1983. [10] At the beginning of the 21st century, insulin pumps (first implemented by John Pickup in 1978 [11]) and intensive selfmonitoring were also applied in people with T2D. [12, 13, 14] Despite of pumps many persons with T2D were unable to reach the expected metabolic improvement until incretin receptor agonists and gliflozins have been made available. [15, 16]
In 1974, the first glucometer (Ames) was introduced into clinical practice, followed by tenths of other glucometers [17, 18, 19], Continuous Glucose Monitors (CGM) [20] and/or Flash Glucose Monitors (FGM) [21]. Today, these devices have become mandatory means (together with HbA1c analysers [22]) to assess the metabolic control. Scientific inventions from the last 100 years were applied in official statements and guidelines. [23, 24, 25]
This overview introduces promoting insights and better understanding of pathophysiologic approach to various treatments of T2D. Purpose of the presented case reports and single-centre „real world trials “is to motivate to education and to implementation of incretins and/or gliflozins and/or insulin analogs and/or insulin pumps in daily routine of diabetes care.
Lifestyle and education of people with chronic disorders have been recognised as an essential part of treatment. Many anonymous dedicated enthusiasts have created a solid platform for effective therapy. Some of them became famous educators, however, most of them remained unnoticed in everyday practice.
The Diabetes Education Study Group (DESG) of the European Association for the Study of Diabetes (EASD), was founded in 1977 [26] and the Therapeutic Patient Education (TPE) became a goal of many respected bodies in the world.
The DESG aimed to improve the quality of life through educational programmes designed to foster independence for the patient, to improve the quality of metabolic control, to emphasise the prevention and to encourage research. The DESG organised activities all over the Europe, published more than 30 Teaching letters and Series of the 5-min education basics. In eastern countries, the DESG workshops (Bucharest, 1982, Balatonfuered, 1985, Warsaw, 1987, Weimar, 1989, Olomouc, 1991) supported the cooperation between health care providers (physicians, teachers, psychologists, nurses, dietitians, social workers) and patients. (Figure 1) Therefore, the adopted 5- day scheduled teaching programs created by Assal, Berger and Jörgens in Genf and Düsseldorf [27] could be spread throughout Europe. Workshops at Grimentz, Capri, Celano, Assisi, Chillworth, Cambridge, Winchester, Windsor, Sesimbra, etc., motivated to look at issues from various angels.
Abstract Book from the last workshop of the Eastern DESG in Olomouc (1991).
Process of TPE consists of three parts: teaching knowledge, training skills and formating attitudes. These principles have also been considered in our pathophysiologic approach to treatment of T2D in daily routine. [28, 29]
Insulin pens opened the door to comfortable insulin administration thereby making the intensive regimens acceptable at work, at school, at leisure, during travels, etc.
In 1983, the first models of a MAnual Device for Insulin (MADI) proved to be a useful aid to injection of U-40 insulin either as a needle pen or as a catheter pen. [10] Within a few years other injectors appeared. [30, 31] Six models of a new type of MADI for insulin U-40, U-80 and U-100 were developed. [32] (Figure 2) In the needle pen (Figure 3) a sliding cover prevents the contamination of the needle which remains invisible in the course of injection and might be reused without sterilization. [33] In the catheter pen (Figure 4) the catheter remained inserted in subcutaneous tissue for 3 days. A syringe-like interchangeable plastic reservoir (3 ml) was refilled from insulin vials with any kind of soluble insulin. Actual insulin administration occurred by twisting the cap after subcutaneous insertion of needle or catheter.
Scheme of MADI: needle pen with telescopic sliding cover (left) and catheter pen [32] (1991).
MADI – needle pen in the course of injection (1994).
MADI – catheter pen [35] (1994).
To date, about one hundred of various types of insulin or incretin needle-pens have been distributed all over the world. (Figure 5) Most of them are disposable pens [34] (prefilled with insulin, to be discarded after emptying), some of them are constructed for cartridged insulin produced by the respective company.
Heaps of insulin or incretin pens produced by different companies all over the world since 1983. Photo V. Kupčik, Diabetes Museum, Háj ve Slezsku, CR. (2019).
Despite initial enthusiasm, the preference of catheter pens [35] (Figure 6) was low over time.
Various catheter pens: MADI (CR), MD2 (GDR), D pen (CH) (1989).
Within the course of 25 years, we have tested the accuracy and precision of glucometer-strips systems Card (Medisense), OPTIUM (Abbott), ADVANCE (Hypoguard, GB) [17] and LINUS (Agamatrix, USA). [18] to support the reliability of our therapeutic recommendations.
The purpose of our last experimental and clinical trial (2010–2013) [19] was (1) to assess the electrochemistry-based glucometers CONTOURLINK (Bayer, Germany) using glucose dehydrogenase strips, CALLA, (Wellion, Austria) and LINUS (Agamatrix, USA) both using glucose oxidase strips; (2) to evaluate diabetes control using Ambulatory Glycaemic Profiles (AGP) and comparing the results with those of the COBAS INTEGRA 400 Plus analyser. There were 112 sets (each from one person) analysed. Means of 3 PG estimations on glucometers and on INTEGRA analyser were calculated.
Strong correlations between PG values estimated on COBAS INTEGRA analyser vs. individual glucometers (CONTOURLINK, CALLA, LINUS) were shown (Figure 7). Deviations from INTEGRA were within the range ± 15%. (Figure 8) PG variability was measured by SD: SD INTEGRA = 0.061 mmol/l, SD CONTOURLINK = 0.256 mmol/l, SD CALLA = 0.290 mmol/l, SD LINUS = 0.286 mmol/l. The mean INTEGRA PG values ranged from 2.7 to 25.3 mmol/l.
Correlations (Spearman) between PG estimations on INTEGRA vs. CALLA [19] (2013).
Relative deviations of glucometer estimations from estimations on analyser Cobas Integra. PG deviations of respective glucometers from INTEGRA PG were within the range ± 15% (i.e. in 94.6%, 93.8%, 97.3% of 112 pairs, resp.) [19] (2013).
All persons with T2D performed 10-point PG profiles to optimise balance between meals, physical exercise, and insulin boluses. PG differences between the respective glucometer-strips system and COBAS INTEGRA laboratory values were in borderline of ISO 15197. [25]. So, the practical acceptability of all tested glucometer-strips systems was demonstrated. Nevertheless, due to different (even though acceptable) accuracy of individual systems, it is advisable to use one type of glucometer-strips system in each diabetes centre. Since 2013 all our patients are trained in SMPG on glucometer CALLA. If insulin pump MINIMED 640 G is used, glucometer CONTOUR PLUS is sometimes preferred due to wireless signal transmission.
In 2005–2013 we tested benefits of CGM in three independent studies. Two of them were performed in people with T2D and T1D treated by insulin pumps PARADIGM (Medtronic MiniMed, Nordthridge, CA, USA). One study aimed to patients without insulin pump in perioperative care.
The pump PARADIGM 722 communicates with CGM and enables daily reading of 288 PG values determined by a SENsor inserted into subcutaneous tissue (PARASEN study). Real-time PG values are helpful to adapt further treatment.
Aim of this clinical study [36] was to compare the evolution of HbA1c over the 3- month period with CGM vs. a period with conventional SMPG by glucometers.
Two cohorts of T1D + T2D on insulin pumps PARADIGM were investigated.
Cohort 1 comprised 17 persons using CGM sensors for continuous glucose monitoring (CGM group). Cohort 2 comprised 25 people performing self-monitoring as before (3 to 6 times/d) on glucometer LINUS, Wellion, Agamatrix (SMPG group). In the CGM group (but not in the SMPG group) HbA1c significantly dropped within one month and remained reduced as long as the CGM was applied, i.e., until the switch back to SMPG. (Figure 9).
Benefits of CGM in individuals on insulin pump [36] (2013).
Hence, continuous glucose monitoring with transcutaneous sensors appeared to be an important measure for improving metabolic compensation in people with diabetes. With CGM, the evolution of HbA1c showed metabolic improvement. The PARASEN study demonstrated that continuous self-monitoring should become a regular part of treatment in educated persons on insulin pumps.
Several years later, the COMISAIR study [37] demonstrated that also a conventional intensive multiple dose insulin regimen (MDI), if supported by CGM, can be a suitable alternative to CGM augmented insulin pump therapy.
The multicenter CGM study (2005–2009) [38] aimed to the assessment of benefits of CGM-augmented insulin pump therapy for persons with T1D.
Community or academic practices in six Central and Eastern European/ Mediterranean countries established a registry of people with T1D starting CGM-augmented insulin pump therapy with the pump PARADIGM® X22 under everyday conditions. We compared HbA1c values before and after 3 months of CGM and assessed relationships between insulin therapy and glycaemia-related variables.
Sensor data and HbA1c data were evaluated in 85 of 102 enrolled persons with longstanding T1D, mean age 33.2 ± 16.9 years. Mean HbA1c declined after 3 months of CGM from 59.0 ± 8.9 mmol/mol at baseline to 50.9 ± 11.7 mmol/mol (P < 0.001).
Hence, CGM-augmented insulin pump therapy appeared to improve glycaemic control in T1D in everyday practice settings.
Our third CGM study (2009–2013) [39] payed attention to the assessment of implementation of CGM in perioperative care of T2D.
PG monitoring was performed by means of GUARDIAN REAL-Time CGMS (Medtronic, Northridge, USA) in perioperative periods of 20 persons with T2D. Sensor was inserted on the day before surgery and continued for 3 days.
This approach was successful in the intensive care unit setting only. Neither electromagnetic interference nor other side effects appeared. No significant difference between sensor and laboratory analyser values was found. Pearson’s correlation coefficients between PG by sensor and by Wellion Linus glucometer during the whole perioperative period were significantly strong (0.9). Hypoglycaemia was registered in 4 of 20 persons.
So, transcutaneous CGM appears to be a safe approach offering a detailed insight into perioperative PG homeostasis. However, confirmation of sensor data by an approved method remains necessary.
Disturbed dynamics of insulin secretion in T2D (Figure 10) makes the need of small complementary preprandial boluses of rapid insulin understandable.
Dynamics of insulin secretion in blood in healthy people (initial postprandial peak is present, insulin concentration returns to baseline within 3 h); in T2D (missing Initial peak, maximum is delayed and hyperinsulinaemia remains over 3 h) [7] (1995).
In the years 1991–2019 we carried out three single centre trials to this topic.
In 1991–1994, a nonrandomized uncontrolled study with 251 T2D assessed the effectiveness of supplementary insulin regimen [40, 41] The complementary insulin therapy using insulin pen MADI started in hospital following the baseline PG profile on day 2. The final ten-point PG profile was performed on day 4. (Figures 11 and 12) At a check-up 8–10 weeks later a decrease of HbA1c, BMI and improved lipoprotein-spectrum was found (Figures 13 and 14).
Ten- point BG profiles (mean ± SE) in insulin-naïve-T2D treated on baseline with oral antidiabetic drugs and/or diet (upper curve) and then with complementary boluses (4 to 6 U each = 26 U/d) of rapid insulin (lower curve) *P < 0,05. [40] (1997).
Ten- point BG profiles (mmol/l, mean ± SE) in T2D treated on baseline with long-acting insulin (1 to 2 boluses/d = 47 U/d) and/or diet and then with complementary boluses (4 to 6 U each = 32 U/d) of rapid insulin (lower curve) *P < 0,05. [40] (1997).
Lipoprotein apoLpA1 at baseline and after 8–10 weeks of complementary insulin therapy [41] (1997).
Lipoprotein apo LpB at baseline and after 8–10 weeks of complementary insulin therapy [41] (1997).
We concluded that in T2D better metabolic control can be achieved with complementary insulin therapy than with oral antidiabetic drugs or long-acting insulin 1–2 times daily. Our “surprising” results were based on pathophysiologic concept of Bruns, Berger and Kalfhaus. [7, 8, 9] To date, intensive insulin therapy in people with T2D appears to be more accepted in daily routine. [6, 23]
The rapid acting insulin anologs (aspart, lispro and glulisin) are available since the end of the 20th century. Their absorption rates prevail over that of regular human insulin. [42, 43]
The aim of our prospective observational open-label controlled study (2004–2007) [44] was to compare the effects of insulin analog aspart and human regular insulin resulting from their routine administration in small preprandial boluses according to identical algorithms.
Fifty-seven persons with T2D aged 64.0 ± 1.29 (mean ± SE) years, diabetes duration of 12.4 ± 1.06 years, C-peptide positive, were enrolled into the study. Their treatment with human regular insulin lasted 5.2 ± 0.44 years. Human regular insulin was replaced with insulin analog aspart. Two check-ups in the course of 330 ± 11.1- day sequential period were carried out. The control group consisted of 17 persons of equivalent age, duration of diabetes and insulin dosing.
Following the switch from human regular insulin to insulin analog aspart, HbA1c concentration in blood decreased Figure 15, while plasma glucose concentrations in 10-point profiles, daily insulin dose, BMI, and frequency of hypo−/hyperglycemic episodes did not change.
Impact of insulin aspart (given according the same algorhithms as human insulin) on HbA1c in 57 persons with T2D (* P < 0,05) [44] (2007).
No significant influence of insulin aspart on serum concentrations of triacylglycerols, total cholesterol, and LDL-cholesterol was found. Patients’ satisfaction was good. No adverse events were recorded. In the control group, no significant changes of baseline HbA1c, insulin dose and BMI were found.
Hence, insulin analog aspart appears to be more effective than human regular insulin in intensive (complementary) treatment in individuals with T2D.
The benefits of faster insulin aspart (insulin aspart + nicotinamid) were described and discussed. [45, 46]
Aim of our prospective monocentric uncontrolled Real World Evidence study (2017–2019) [47] was to compare the efficacy of FIASP with the efficacy of previous therapy with insulin aspart in people with T1D and T2D on MDI or on insulin pump.
No adverse events appeared in any group. In T2D groups (N < 24) an unsignificant tendency to reduction of PG, MPG, HbA1c, body mass and total daily dose of insulin in the course of FIASP therapy was shown.
So, only the evidence of noninferiority of FIASP versus insulin aspart was demonstrated. Introduction of improved algorithms together with intensive patients´ education appears necessary to improve the expected outcomes of FIASP therapeutic regimen.
The effectiveness of CSII in T2D was sought for in many previous studies [48, 49, 50, 51, 52]. Our (Medtronic supported) prospective single-centre randomized study (2011–2014) [53, 54, 55] recruited 36 insulin-resistant, C-peptide-positive, glutamic acid decarboxylase antibodies (GAD Ab)-negative, and CSII-naive patients with T2D (eight screen failures). Insulin treatment was optimized with insulin analogs and metformin. Following the run-in period, patients were randomized into two arms: a CSII arm (n = 11) and an MDI continuation arm (n = 12). HbA1c ≥ 64 mmol/mol, (mean ± standard deviation), age of 57.2 ± 8.0 years, BMI of 36.2 ± 7.0 kg/m2, BM of 106.9 ± 18.3 kg, diabetes duration of 13.3 ± 4.7 years, and HbA1c of 80 mmol/mol). In both arms, at the CSII start the daily insulin dose was reduced by 10% –50% in order not to exceed 80 U/day. After 6 months, persons receiving MDI crossed over to insulin pump and both arms were followed up during consequent 6 months. A total of 10 scheduled visits were carried out in each arm. The final Visit 10 occurred at 12 months. The mean frequency of self-monitoring varied between 3.4 and 5.4 measurements per day.
Patients assigned to the CSII arm (N = 11) achieved a significant HbA1c reduction of 10–12 mmol/mol while reducing their daily insulin dose by 33% of baseline; BMI reduction was 0.86% of baseline. No significant changes were revealed in patients on MDI Figure 16.
HbA1c (top) and total daily insulin dose (bottom) in the MDI/CSII arm (N = 11, closed symbols) and in the CSII/CSII arm (N = 11, open symbols). Symbols and bars - mean and 95% CI (confidence interval); CSII - continuous subcutaneous insulin infusion; MDI - multiple daily injections [55] (2017).
So, the use of insulin pump (supported with SMBG) in T2D is safe and effective for improving glucose control and reducing daily dose of insulin. Treatment adherence and satisfaction were excellent. All subjects decided to continue using their insulin pumps. On the other hand, an optimum metabolic balance and sustainable reduction in body mass, blood pressure or lipid profile in most of the patients could not be reached.
The first incretin analogs exenatid [56], lixisenatid, liraglutide were used in persons with T2D to improve metabolic control and to reduce body mass - mostly when HbA1c exceeded 60 mmol/mol, BMI was over 35 kg/m2 and oral antidiabetic drugs failed. Their beneficial metabolic and cardiovascular effects were described recently in RCTs LEAD 1 – LEAD 6 [57, 58, 59, 60, 61, 62] and LEADER. [63] We had the option to confirm their benefits in several persons.
Our case report from the year 2010 [64] demonstrates the benefits of treatment with liraglutide in a 57-year old obese woman (adequately treated for hypothyreosis) with recent evolution of metabolic syndrome. Four-month metformin (M) and liraglutide (L) therapy reduced both body mass index (Figure 17), and glycated haemoglobin (Figure 18) Even though the previous diabetes control was acceptable, the treatment with high doses oť metformin and sitagliptin (S) failed to reach sufficient reduction of body mass and HbA1c.
Lady, age 57. Therapy and evolution of BMI since the detection of T2D in 2006. M-metformin, S-sitagliptin, L-liraglutide (L-start 18.8.2010) [64].
Lady, age 57. Therapy and evolution of HbA1c since the detection of T2D in 2006. M-metformin, S-sitagliptin, L-liraglutide (L-start 18.8.2010) [64].
Our second case report (2010–2016) [65] deals with a temporal positive influence of a 5-year liraglutide therapy on HbA1c (Figure 19), BMI and 10-point glyceamic profile in a man with 13-year history of uncontrolled T2D. After one year on liraglutide 1,2 mg/d + metformin 2000–3000 mg/d, the initial decrease of BMI and HbA1c was followed by their slow increase. Following bariatric surgery, the continuing liraglutide and metformin treatment resulted in near-normal HbA1c concentrations not exceeding 51 mmol/mol. The BMI decreased from 39 to 32 kg/m2.
Man, age 57 y, T2D duration 13 y. Evolution of HbA1c with liraglutide and metformin before (2010–2012, blue) and after (2012–2015) bariatric surgery [65] (2015).
The purpose of this case report (2011) [66] is to demonstrate the effects of 5- month off label administration of L and metformin (M) in a 60y old woman with impaired fasting plasma glucose (IFG), BMI 36.4 kg/m2, HbA1c 41 mmol/mol and in excellent physical condition. Since 2005 her body mass increased by 10 kg. Recently diagnosed hypertension was successfully treated by metoprolol and losartan (BP 140/80 mmHg, HF 64/min). She was treated by simvastatin since 2008 (LDL cholesterol 3,4 mmol/l). Proinsulin, C-peptide, TSH. T3, T4 and routine laboratory parameters were found within normal limits. Results of SMPG using glucometer Linus, Agamatrix, USA were slightly abnormal. In August 2010 the therapy with L and M started. First evaluation was made in January 2011 (Figures 20 and 21). In 2012 – 2014, L 1.2 mg/d was given only during a 3- month period each year. Then, M 2 g/d continued without L. Food intake was reduced due to lasting satiety. The final check up in February 2021 revealed excellent clinical condition, BM 66.1 kg, BMI 29.4 kg/m2 and HbA1c 39 mmol/mol.
Lady, age 60 y, prediabetes. Evolution of body mass before and with L + M [66] (2011).
Lady, age 60 y, prediabetes. 10-point PG profile before and with L + M [66] (2011).
Independently, 4 of other 6 obese persons with IFG/IGT reduced body mass during L supplementation. So, L therapy appears to be a potentially effective approach to prediabetes conditions and its administration should start rather at an early stage.
Effects of long-acting incretin analogs (exenatid QW, dulaglutid [67] and semaglutide [68, 69, 70, 71, 72, 73, 74, 75, 76, 77] on metabolism, cardiovascular and renal protection were described in clinical studies REWIND and SUSTAIN 1–10, resp.
Our case report (2019–2020) [78] brings insight on benefits of semaglutide in a 79-year-old lady with long-lasting T2D. She has been suffering from both metformin intolerance and insulinofobia. In the course of a long- lasting period of gliptin therapy, the patient’s HbA1c concentration increased to 61 mmol/mol. During the following 4-month period with semaglutide, the patient’s mean PG concentration of a 10-point daily profile (MPG) decreased from 7.4 mmol/l to 7.0 mmol/l, and her body mass from 80,9 kg to 77,7 kg. One year later, the HbA1c reached 48 mmol/mol (Figure 22). No adverse events appeared. We can conclude, the early indication of once-a-week subcutaneously administered semaglutide resulted in improvement of all investigated parameters of saccharide metabolism.
Lady, age 79 y. Evolution of HbA1c in the course of treatment with saxagliptin, linagliptin and semaglutide, resp., 2018 to 2020 [78].
Metabolic and cardiovascular benefits of the fixed combination IdegLira were evaluated in studies DUAL and others. [79, 80, 81, 82, 83, 84, 85, 86, 87]
We deemed IDegLira could be an option for T2D suffering from impaired cognitive functions. We described this condition as “cast away syndrome”.
Our case report (1995–2020) [88] pays attention to IDegLira in a 77-year-old woman with T2D. Her diabetes was treated for 33 years (since 1985) including the last seven- year period of effective insulin pump therapy, finally combined with dapagliflozin. Recently, signs of cognitive deterioration (“cast away syndrome”) appeared and the patient was unable to operate her insulin pump. Adding IDegLira to previous metformin and dapagliflozin therapy alongside with support of educated family lead to improvement of patient’s condition. The final in-patient period (30. 4. - 1. 7. 2020]) with IDegLira 40 IU/d (no CSII, no metformin, no gliflozin) and specialized diabetes care of nursing staff resulted in reduction of HbA1c to 38 mmol/mol (reference range 20–42 mmol/mol) (Figure 23–25).
Lady, age 77 y, T2D since 1985, cast away syndrome. Evolution of HbA1c in the course of different therapy (MDI-CSII-CSII with iSGLT2-IDegLira only) (1997–2020) [88].
Lady, age 77 y, T2D since 1985, cast away syndrome. Evolution of BM in the course of different therapy (MDI-CSII-CSII with iSGLT2-IDegLira only) (1995–2020) [88].
Lady, age 77 y, T2D since 1985, cast away syndrome. Overview of all parameters (HbA1c, BM, insulin/day, MPG) in the course of different therapeutic regimens (MDI-CSII-CSII with iSGLT2-IDegLira only) (1996–2020) [88].
Gliflozins are inhibitors of sodium glucose co-transporter 2 (SGLT2) in proximal part of renal tubules. Their influence results in lowering of the renal thresholds for glucose and lowering of hyperglycaemia (due to urine excretion of about 70 g glucose per 24 h). Impact of gliflozins (dapagliflozin [89, 90, 91], empagliflozin [92] canagliflozin [93, 94, 95] and ertugliflozin) on metabolic control and cardiovascular and renal outcomes in T2D was demonstrated in trials EMPAREG, EMPEROR, CANVAS, CREDENCE, DECLARE HF, DECLARE Timi 58 and VERTIS. Benefits were observed in simultaneous therapy with insulin/incretin and gliflozin. [96]
Our pilot prospective trial (2015–2017) [97] aimed to the assessment of effectiveness of dapagliflozin added to people with T2D treated by CSII and metformin (M). A group of 13 T2D on CSII, without serious complications, aged 44.6–70.4 y, diabetes duration 5–26 y, BMI 24.9–57.6 kg/m2, were monitored at 4 visits (before CSII, on CSII + M, on CSII + M shortly before dapagliflozin and finaly on CSII + M after 2.5–11.0 months with dapagliflozin.
CSII appeared to enable reduction of total daily insulin dose with no consequent change of HbA1c and glycaemia. Adding dapagliflozin to CSII resulted in significant reduction of HbA1c. (Figure 26) Even though the change in BM was not significant, Spearman analysis revealed correlations between the change of daily insulin dose and change of BM at visit 3 and 4 vs. visit 1.
A group of T2D (N = 13) treated with 3 consequent regimens: 1. MDI + M, 2. CSII+M, 3. CSII+M + DG. Evolution of relative values of INS/d, HbA1c, MPG, BM. Upper border of the reference range of respective parameter was defined as 100% of its value (2015–2017) [97].
No side effects appeared. So, dapagliflozin may be considered as a rational therapeutic addition to CSII + M treated people with T2D.
This chapter summarizes the authors’ experience along with outcomes of respected randomized control trials and real world evidence studies. It became clear that the pathophysiologic approach comprising insulin, incretins and gliflozins has created a reliable base to effective treatment of type 2 diabetes. Reduced morbidity and mortality along with other breaking reports [98, 99, 100, 101] are offerring some great perspectives.
On the other hand, in everyday practice, hidden clinical inertia, resulting from outdated treatment approach, customs, imbalance between powerty and affluency, should be considered as a dangerous rival.
So, which direction do we take from here?
R.C. was in charge of the selection of cited references and figures and manuscript design, data analysis and critical text review. R.K. and L.H. supervised the performance of therapeutic protocols including HbA1c and 10-point glycaemic profiles, H.Z. was responsible for medical reports, files and IT operations, B.D. took care of laboratory investigations. There is no conflict of interests.
Special thanks to Stanislava Dudová, Emilia Ďurajková, Lenka Kratochvílová, Michaela Nádvorniková, Jana Polcerová, Svatava Tancosová, Jana Ferancová, Pavel Kolčava, Eva Malá, Dana Masnikosová, Hana Peniaková, Jiří Podivínský, Jana Svobodová, Rastislav Šramko and their teams for outstanding neverending support.
Final acknowledgement belongs to specialists, nursing and other staff, students of Palacky University Olomouc, compliant persons with diabetes, as well as to Insurance Companies and pharma industry in the Czech Republic.
Those who found this chapter worthy of reading surely appreciate the support provided by Palacky University, Teaching Hospital Olomouc, Institute of Specialized Treatments Paseka and other important institutions.
Taking into account the dawning observations of Paul Langerhans (1847–1888) [102], Oskar Minkowski (1858–1931) [103], George Ludwig Zülzer (1870–1949) [104], Ernest Lyman Scott ((1877–1966) [105] and others in [106, 107], this paper was written in the memory of Nicolae Constantin Paulescu (1869–1931), James Bertram Collip (1892–1965), Frederick Grant Banting (1891–1941), Charles Herbert Best (1899–1978) and John James Rickard Macleod (1876–1935) on the occasion of the 100-year anniversary of insulin (pancrein) discovery (Bucharest, May 1921) [4], and its purification and implementation to human medicine (Toronto, January 1922) [5].
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