Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Type 1 Diabetes and Physical Exercise: Moving (forward) as an Adjuvant Therapy

Author(s): Othmar Moser*, Max L. Eckstein, Daniel J. West, Nandu Goswami, Harald Sourij and Peter Hofmann

Volume 26, Issue 9, 2020

Page: [946 - 957] Pages: 12

DOI: 10.2174/1381612826666200108113002

Price: $65

Abstract

Type 1 diabetes is characterized by an autoimmune β-cell destruction resulting in endogenous insulin deficiency, potentially leading to micro- and macrovascular complications. Besides an exogenous insulin therapy and continuous glucose monitoring, physical exercise is recommended in adults with type 1 diabetes to improve overall health. The close relationship between physical exercise, inflammation, muscle contraction, and macronutrient intake has never been discussed in detail about type 1 diabetes. The aim of this narrative review was to detail the role of physical exercise in improving clinical outcomes, physiological responses to exercise and different nutrition and therapy strategies around exercise.

Physical exercise has several positive effects on glucose uptake and systemic inflammation in adults with type 1 diabetes. A new approach via personalized therapy adaptations must be applied to target beneficial effects on complications as well as on body weight management. In combination with pre-defined macronutrient intake around exercise, adults with type 1 diabetes can expect similar physiological responses to physical exercise, as seen in their healthy counterparts.

This review highlights interesting findings from recent studies related to exercise and type 1 diabetes. However, there is limited research available accompanied by a proper number of participants in the cohort of type 1 diabetes. Especially for this group of patients, an increased understanding of the impact of physical exercise can improve its effectiveness as an adjuvant therapy to move (forward).

Keywords: Physical exercise, Type 1 diabetes, GLUT-4, inflammation, insulin therapy, autoimmune β-cell destruction.

[1]
Gepts W. Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 1965; 14(10): 619-33.
[http://dx.doi.org/10.2337/diab.14.10.619] [PMID: 5318831]
[2]
Tisch R, McDevitt H. Insulin-dependent diabetes mellitus. Cell 1996; 85(3): 291-7.
[http://dx.doi.org/10.1016/S0092-8674(00)81106-X] [PMID: 8616883]
[3]
Smith EL, Peakman M. Peptide immunotherapy for type 1 diabetes-clinical advances. Front Immunol 2018; 9: 392.
[http://dx.doi.org/10.3389/fimmu.2018.00392] [PMID: 29541078]
[4]
Kopan C, Tucker T, Alexander M, Mohammadi MR, Pone EJ, Lakey JRT. Approaches in immunotherapy, regenerative medicine and bioengineering for type 1 diabetes. Front Immunol 2018; 9: 1354.
[http://dx.doi.org/10.3389/fimmu.2018.01354] [PMID: 29963051]
[5]
Chiang JL, Kirkman MS, Laffel LMB, Peters AL. Type 1 Diabetes Sourcebook Authors. Type 1 diabetes through the life span: a position statement of the American Diabetes Association. Diabetes Care 2014; 37(7): 2034-54.
[http://dx.doi.org/10.2337/dc14-1140] [PMID: 24935775]
[6]
Danne T, Nimri R, Battelino T, et al. International consensus on use of continuous glucose monitoring. Diabetes Care 2017; 40(12): 1631-40.
[http://dx.doi.org/10.2337/dc17-1600] [PMID: 29162583]
[7]
Heise T, Meiffren G, Alluis B, et al. BioChaperone Lispro versus faster aspart and insulin aspart in patients with type 1 diabetes using continuous subcutaneous insulin infusion: A randomized euglycemic clamp study. Diabetes Obes Metab 2018; 21: 1066-70.
[http://dx.doi.org/10.1111/dom.13621] [PMID: 30565407]
[8]
Davis CS, Fleming JW, Malinowski SS, Brown MA, Fleming LW. Ultra-long-acting insulins: A review of efficacy, safety, and implications for practice. J Am Assoc Nurse Pract 2018; 30(7): 373-80.
[http://dx.doi.org/10.1097/JXX.0000000000000076] [PMID: 29979295]
[9]
Bergenstal RM, Garg S, Weinzimer SA, et al. Safety of a hybrid closed-loop insulin delivery system in patients with type 1 diabetes. JAMA 2016; 316(13): 1407-8.
[http://dx.doi.org/10.1001/jama.2016.11708] [PMID: 27629148]
[10]
Foster NC, Beck RW, Miller KM, et al. State of type 1 diabetes management and outcomes from the t1d exchange in 2016-2018. Diabetes Technol Ther 2019; 21(2): 66-72.
[http://dx.doi.org/10.1089/dia.2018.0384] [PMID: 30657336]
[11]
Nathan DM. DCCT/EDIC Research Group. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview. Diabetes Care 2014; 37(1): 9-16.
[http://dx.doi.org/10.2337/dc13-2112] [PMID: 24356592]
[12]
Heyman E, Delamarche P, Berthon P, et al. Alteration in sympathoadrenergic activity at rest and during intense exercise despite normal aerobic fitness in late pubertal adolescent girls with type 1 diabetes. Diabetes Metab 2007; 33(6): 422-9.
[http://dx.doi.org/10.1016/j.diabet.2007.10.003] [PMID: 18035572]
[13]
Malik A, Morya RK, Bhadada SK, Rana S. Type 1 diabetes mellitus: Complex interplay of oxidative stress, cytokines, gastrointestinal motility and small intestinal bacterial overgrowth. Eur J Clin Invest 2018; 48(11): e13021
[http://dx.doi.org/10.1111/eci.13021] [PMID: 30155878]
[14]
Riddell MC, Gallen IW, Smart CE, et al. Exercise management in type 1 diabetes: a consensus statement. Lancet Diabetes Endocrinol 2017; 5(5): 377-90.
[http://dx.doi.org/10.1016/S2213-8587(17)30014-1] [PMID: 28126459]
[15]
Tero R, Fukumoto K, Motegi T, Yoshida M, Niwano M, Hirano-Iwata A. Formation of cell membrane component domains in artificial lipid bilayer. Sci Rep 2017; 7(1): 17905.
[http://dx.doi.org/10.1038/s41598-017-18242-9] [PMID: 29263355]
[16]
Scheepers A, Joost HG, Schürmann A. The glucose transporter families SGLT and GLUT: molecular basis of normal and aberrant function. JPEN J Parenter Enteral Nutr 2004; 28(5): 364-71.
[http://dx.doi.org/10.1177/0148607104028005364] [PMID: 15449578]
[17]
M Elizabeth, DB Melena. Secretion of insulin in response to diet and hormones Pancreapedia Exocrine Pancreas Knowl Base 2016. Available at: https://www.pancreapedia.org/reviews/secretion-of-insulin-in-response-to-diet-and-hormones
[http://dx.doi.org/10.3998/PANC.2016.3]
[18]
Mueckler M, Caruso C, Baldwin SA, et al. Sequence and structure of a human glucose transporter. Science 1985; 229(4717): 941-6.
[19]
Wood IS, Trayhurn P. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 2003; 89(1): 3-9.
[http://dx.doi.org/10.1079/BJN2002763] [PMID: 12568659]
[20]
Leto D, Saltiel AR. Regulation of glucose transport by insulin: traffic control of GLUT4. Nat Rev Mol Cell Biol 2012; 13(6): 383-96.
[http://dx.doi.org/10.1038/nrm3351] [PMID: 22617471]
[21]
Junge W, Nelson N. ATP synthase. Annu Rev Biochem 2015; 84: 631-57.
[http://dx.doi.org/10.1146/annurev-biochem-060614-034124] [PMID: 25839341]
[22]
Bonora M, Patergnani S, Rimessi A, et al. ATP synthesis and storage. Purinergic Signal 2012; 8(3): 343-57.
[http://dx.doi.org/10.1007/s11302-012-9305-8] [PMID: 22528680]
[23]
Kraegen E, James DE, Jenkins AB, Chisholm DJ. Dose-response curves for in vivo insulin sensitivity in individual tissues in rats. 1985; 248: E3-353.
[http://dx.doi.org/10.1152/ajpendo.1985.248.3.E353]
[24]
Division E, Israel B, Medical D. Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat Med 2020; 6: 4-8.
[25]
Wardzala LJ. Cushmann Sw, Salans L. Mechanism of insulin action on glucose transport in the isolated rat adipose cell. J Biol 1978; 253: 8002-5.
[26]
Huang S, Czech MP. The GLUT4 glucose transporter. Cell Metab 2007; 5(4): 237-52.
[http://dx.doi.org/10.1016/j.cmet.2007.03.006] [PMID: 17403369]
[27]
Richter EA, Hargreaves M. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev 2013; 93(3): 993-1017.
[http://dx.doi.org/10.1152/physrev.00038.2012] [PMID: 23899560]
[28]
Christensen EH, Hansen O. Glucose metabolism during leg exercise in man. J Clin Invest 1938; 1971(50): 2715-25.
[29]
Wahren J, Felig P, Ahlborg G, Jorfeldt L. Glucose metabolism during leg exercise in man. J Clin Invest 1971; 50(12): 2715-25.
[http://dx.doi.org/10.1172/JCI106772] [PMID: 5129319]
[30]
Ahlborg G, Felig P, Hagenfeldt L, Hendler R, Wahren J. Substrate turnover during prolonged exercise in man. Splanchnic and leg metabolism of glucose, free fatty acids, and amino acids. J Clin Invest 1974; 53(4): 1080-90.
[http://dx.doi.org/10.1172/JCI107645] [PMID: 4815076]
[31]
Coyle EF, Hagberg JM, Hurley BF, Martin WH, Ehsani AA, Holloszy JO. Carbohydrate feeding during prolonged strenuous exercise can delay fatigue. J Appl Physiol 1983; 55(1 Pt 1): 230-5.
[http://dx.doi.org/10.1152/jappl.1983.55.1.230] [PMID: 6350247]
[32]
Birnbaum MJ. Identification of a novel gene encoding an insulin-responsive glucose transporter protein. Cell 1989; 57(2): 305-15.
[http://dx.doi.org/10.1016/0092-8674(89)90968-9] [PMID: 2649253]
[33]
Charron MJ, Brosius FC III, Alper SL, Lodish HF. A glucose transport protein expressed predominately in insulin-responsive tissues. Proc Natl Acad Sci USA 1989; 86(8): 2535-9.
[http://dx.doi.org/10.1073/pnas.86.8.2535] [PMID: 2649883]
[34]
Stöckli J, Fazakerley DJ, James DE. GLUT4 exocytosis. J Cell Sci 2011; 124(Pt 24): 4147-59.
[http://dx.doi.org/10.1242/jcs.097063] [PMID: 22247191]
[35]
Hou JC, Pessin JE. Ins (endocytosis) and outs (exocytosis) of GLUT4 trafficking. Curr Opin Cell Biol 2007; 19(4): 466-73.
[http://dx.doi.org/10.1016/j.ceb.2007.04.018] [PMID: 17644329]
[36]
Constable SH, Favier RJ, Cartee GD, Young DA, Holloszy JO. Muscle glucose transport: interactions of in vitro contractions, insulin, and exercise. J Appl Physiol 1988; 64(6): 2329-32.
[http://dx.doi.org/10.1152/jappl.1988.64.6.2329] [PMID: 3136124]
[37]
Coderre L, Kandror KV, Vallega G, Pilch PF. Identification and characterization of an exercise-sensitive pool of glucose transporters in skeletal muscle. J Biol Chem 1995; 270(46): 27584-8.
[http://dx.doi.org/10.1074/jbc.270.46.27584] [PMID: 7499220]
[38]
Kong X, Manchester J, Salmons S C J, H J. Glucose transporters in single skeletal muscle fibers. Relationship to hexokinase and regulation by contractile activity. Biochemistry 1994; 269(17): 12963-7.
[39]
Richardson JM, Pessin JE. Abundance, localization, and insulin-induced translocation of glucose transporters in red and white muscle. Am J Physiol 1992; 263(2 Pt 1): C443-52.
[40]
Daugaard JR, Nielsen JN, Kristiansen S, Andersen JL, Hargreaves M, Richter EA. Fiber type-specific expression of GLUT4 in human skeletal muscle: influence of exercise training. Diabetes 2000; 49(7): 1092-5.
[http://dx.doi.org/10.2337/diabetes.49.7.1092] [PMID: 10909963]
[41]
Megeney LA, Neufer PD, Dohm GL, et al. Effects of muscle activity and fiber composition on glucose transport and GLUT-4. Am J Physiol 1993; 264(4 Pt 1): E583-93.
[PMID: 8476037]
[42]
Hansen PA, Nolte LA, Chen MM, Holloszy JO. Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport after exercise. J Appl Physiol 1998; 85(4): 1218-22.
[http://dx.doi.org/10.1152/jappl.1998.85.4.1218] [PMID: 9760308]
[43]
Zorzano A, Balon TW, Goodman MN, Ruderman NB. Glycogen depletion and increased insulin sensitivity and responsiveness in muscle after exercise. Am J Physiol 1986; 251(6 Pt 1): E664-9.
[http://dx.doi.org/10.1152/ajpendo.1986.251.6.e664] [PMID: 3538900]
[44]
M Lehnen A. Changes in the GLUT4 expression by acute exercise, exercise training and detraining in experimental models. J Diabetes Metab 2013; 1(Suppl. 10).
[http://dx.doi.org/10.4172/2155-6156.S10-002]
[45]
Foley K, Boguslavsky S, Klip A. Endocytosis, recycling, and regulated exocytosis of glucose transporter 4. Biochemistry 2011; 50(15): 3048-61.
[http://dx.doi.org/10.1021/bi2000356] [PMID: 21405107]
[46]
Rabasa-Lhoret R, Bourque J, Ducros F, Chiasson JL. Guidelines for premeal insulin dose reduction for postprandial exercise of different intensities and durations in type 1 diabetic subjects treated intensively with a basal-bolus insulin regimen (ultralente-lispro). Diabetes Care 2001; 24(4): 625-30.
[http://dx.doi.org/10.2337/diacare.24.4.625] [PMID: 11315820]
[47]
Moser O, Tschakert G, Mueller A, et al. Effects of high-intensity interval exercise versus moderate continuous exercise on glucose homeostasis and hormone response in patients with type 1 diabetes mellitus using novel ultra-long-acting insulin. PLoS One 2015; 10(8): e0136489
[http://dx.doi.org/10.1371/journal.pone.0136489] [PMID: 26317981]
[48]
Shetty VB, Fournier PA, Davey RJ, et al. Effect of exercise intensity on glucose requirements to maintain euglycemia during exercise in type 1 diabetes. J Clin Endocrinol Metab 2016; 101(3): 972-80.
[http://dx.doi.org/10.1210/jc.2015-4026] [PMID: 26765581]
[49]
Campbell MD, Walker M, Trenell MI, et al. Large pre- and postexercise rapid-acting insulin reductions preserve glycemia and prevent early- but not late-onset hypoglycemia in patients with type 1 diabetes. Diabetes Care 2013; 36(8): 2217-24.
[http://dx.doi.org/10.2337/dc12-2467] [PMID: 23514728]
[50]
Kennedy A, Nirantharakumar K, Chimen M, et al. Does exercise improve glycaemic control in type 1 diabetes? A systematic review and meta-analysis. PLoS One 2013; 8(3): e58861
[http://dx.doi.org/10.1371/journal.pone.0058861] [PMID: 23554942]
[51]
Adamo M, Codella R, Casiraghi F, et al. Active subjects with autoimmune type 1 diabetes have better metabolic profiles than sedentary controls. Cell Transplant 2017; 26(1): 23-32.
[http://dx.doi.org/10.3727/096368916X693022] [PMID: 27983910]
[52]
Tanenberg RJ, Newton CA, Drake AJ. Confirmation of hypoglycemia in the “dead-in-bed” syndrome, as captured by a retrospective continuous glucose monitoring system. Endocr Pract 2010; 16(2): 244-8.
[http://dx.doi.org/10.4158/EP09260.CR] [PMID: 19833577]
[53]
Brazeau A-S, Rabasa-Lhoret R, Strychar I, Mircescu H. Barriers to physical activity among patients with type 1 diabetes. Diabetes Care 2008; 31(11): 2108-9.
[http://dx.doi.org/10.2337/dc08-0720] [PMID: 18689694]
[54]
Campbell MD, Walker M, Bracken RM, et al. Insulin therapy and dietary adjustments to normalize glycemia and prevent nocturnal hypoglycemia after evening exercise in type 1 diabetes: a randomized controlled trial. BMJ Open Diabetes Res Care 2015; 3(1): e000085-5.
[http://dx.doi.org/10.1136/bmjdrc-2015-000085] [PMID: 26019878]
[55]
Moser O, Eckstein ML, Mueller A, Birnbaumer P, Aberer F, Koehler G, et al. Reduction in insulin degludec dosing for multiple exercise sessions improves time spent in euglycaemia in people with type 1 diabetes: a randomised crossover trial. Diabetes Obes Metab 2018; 21(2): 349-56.
[http://dx.doi.org/10.1111/dom.13534] [PMID: 30221457]
[56]
Moser O, Eckstein ML, Mueller A, et al. Pre-Exercise blood glucose levels determine the amount of orally administered carbohydrates during physical exercise in individuals with type 1 diabetes-a randomized cross-over trial. Nutrients 2019; 11(6): 1287.
[http://dx.doi.org/10.3390/nu11061287] [PMID: 31174360]
[57]
MCCARTHY O. 67-LB: time spent in glycaemic ranges and carbohydrate intake during cycling in professional cyclists with type 1 diabetes. Diabetes 2019; 68: 67.
[58]
Zaharieva DP, McGaugh S, Pooni R, Vienneau T, Ly T, Riddell MC. Improved open-loop glucose control with basal insulin reduction 90 minutes before aerobic exercise in patients with type 1 diabetes on continuous subcutaneous insulin infusion. Diabetes Care 2019; 42(5): 824-31.
[http://dx.doi.org/10.2337/dc18-2204] [PMID: 30796112]
[59]
Roy-Fleming A, Taleb N, Messier V, et al. Timing of insulin basal rate reduction to reduce hypoglycemia during late post-prandial exercise in adults with type 1 diabetes using insulin pump therapy: A randomized crossover trial. Diabetes Metab 2019; 45(3): 294-300.
[http://dx.doi.org/10.1016/j.diabet.2018.08.002] [PMID: 30165156]
[60]
Moser O, Tschakert G, Mueller A, et al. Effects of high-intensity interval exercise versus moderate continuous exercise on glucose homeostasis and hormone response in patients with type 1 diabetes mellitus using novel ultra-long-acting insulin. PLoS One 2015; 28; 10(8): e0136489.
[http://dx.doi.org/10.1371/journal.pone.0136489]
[61]
Maran A, Pavan P, Bonsembiante B, et al. Continuous glucose monitoring reveals delayed nocturnal hypoglycemia after intermittent high-intensity exercise in nontrained patients with type 1 diabetes. Diabetes Technol Ther 2010; 12(10): 763-8.
[http://dx.doi.org/10.1089/dia.2010.0038] [PMID: 20807120]
[62]
Moser O, Mader JK, Tschakert G, et al. Accuracy of continuous glucose monitoring (CGM) during continuous and high-intensity interval exercise in patients with type 1 diabetes mellitus. Nutrients 2016; 8(8): 489.
[http://dx.doi.org/10.3390/nu8080489] [PMID: 27517956]
[63]
Chavanelle V, Boisseau N, Otero YF, et al. Effects of high-intensity interval training and moderate-intensity continuous training on glycaemic control and skeletal muscle mitochondrial function in db/db mice. Sci Rep 2017; 7(1): 204.
[http://dx.doi.org/10.1038/s41598-017-00276-8] [PMID: 28303003]
[64]
Guelfi KJ, Ratnam N, Smythe GA, Jones TW, Fournier PA. Effect of intermittent high-intensity compared with continuous moderate exercise on glucose production and utilization in individuals with type 1 diabetes. Am J Physiol Endocrinol Metab 2007; 292(3): E865-70.
[http://dx.doi.org/10.1152/ajpendo.00533.2006] [PMID: 17339500]
[65]
Turner D, Luzio S, Gray BJ, et al. Impact of single and multiple sets of resistance exercise in type 1 diabetes. Scand J Med Sci Sports 2015; 25(1): e99-e109.
[http://dx.doi.org/10.1111/sms.12202] [PMID: 24646137]
[66]
Yardley JE, Kenny GP, Perkins BA, et al. Resistance versus aerobic exercise: acute effects on glycemia in type 1 diabetes. Diabetes Care 2013; 36(3): 537-42.
[http://dx.doi.org/10.2337/dc12-0963] [PMID: 23172972]
[67]
Eshghi SRT, Yardley JE. Morning (fasting) vs. afternoon resistance exercise in individuals with type 1 diabetes: a randomized cross-over study. J Clin Endocrinol Metab 2019; 104(11): 5217-24.
[http://dx.doi.org/10.1210/jc.2018-02384]
[68]
O’Neal TB, Luther EE. Dawn Phenomenon StatPearls Publishing; 2019. Available at: http://www.ncbi.nlm.nih.gov/pubmed/28613643
[69]
Heise T, Meneghini LF. Insulin stacking versus therapeutic accumulation: understanding the differences. Endocr Pract 2014; 20(1): 75-83.
[http://dx.doi.org/10.4158/EP13090.RA] [PMID: 24013982]
[70]
Hofmann P, Tschakert G. Special needs to prescribe exercise intensity for scientific studies. Cardiol Res Pract 2010; 2011: 209302
[http://dx.doi.org/10.4061/2011/209302] [PMID: 21197479]
[71]
Tschakert G, Hofmann P. High-intensity intermittent exercise: methodological and physiological aspects. Int J Sports Physiol Perform 2013; 8(6): 600-10.
[http://dx.doi.org/10.1123/ijspp.8.6.600] [PMID: 23799827]
[72]
Park SW, Goodpaster BH, Strotmeyer ES, et al. Health, Aging, and Body Composition Study. Accelerated loss of skeletal muscle strength in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes Care 2007; 30(6): 1507-12.
[http://dx.doi.org/10.2337/dc06-2537] [PMID: 17363749]
[73]
Mori H, Kuroda A, Araki M, et al. Advanced glycation end-products are a risk for muscle weakness in Japanese patients with type 1 diabetes. J Diabetes Investig 2017; 8(3): 377-82.
[http://dx.doi.org/10.1111/jdi.12582] [PMID: 27727515]
[74]
Hirata Y, Nomura K, Senga Y, et al. Hyperglycemia induces skeletal muscle atrophy via a WWP1/KLF15 axis. JCI Insight 2019; 4(4): 124952
[http://dx.doi.org/10.1172/jci.insight.124952] [PMID: 30830866]
[75]
Hamilton DL, Baar K. Muscle growth: no IGFs, ands, or buts. J Physiol 2008; 586(1): 5-6.
[http://dx.doi.org/10.1113/jphysiol.2007.147660] [PMID: 18167368]
[76]
Ross LM, Porter RR, Durstine JL. High-intensity interval training (HIIT) for patients with chronic diseases. J Sport Health Sci 2016; 5(2): 1-6.
[77]
Schwingshackl L, Dias S, Strasser B, Hoffmann G. Impact of different training modalities on anthropometric and metabolic characteristics in overweight/obese subjects: a systematic review and network meta-analysis. PLoS One 2013; 8(12): e82853
[http://dx.doi.org/10.1371/journal.pone.0082853] [PMID: 24358230]
[78]
Schwingshackl L, Missbach B, Dias S, König J, Hoffmann G. Impact of different training modalities on glycaemic control and blood lipids in patients with type 2 diabetes: a systematic review and network meta-analysis. Diabetologia 2014; 57(9): 1789-97.
[http://dx.doi.org/10.1007/s00125-014-3303-z] [PMID: 24996616]
[79]
Devaraj S, Glaser N, Griffen S, Wang-Polagruto J, Miguelino E, Jialal I. Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes. Diabetes 2006; 55(3): 774-9.
[http://dx.doi.org/10.2337/diabetes.55.03.06.db05-1417] [PMID: 16505242]
[80]
Basu S, Larsson A, Vessby J, Vessby B, Berne C. Type 1 diabetes is associated with increased cyclooxygenase- and cytokine-mediated inflammation. Diabetes Care 2005; 28(6): 1371-5.
[http://dx.doi.org/10.2337/diacare.28.6.1371] [PMID: 15920054]
[81]
Roy MS, Janal MN, Crosby J, Donnelly R. Plasma markers of inflammation and prediction of cardiovascular disease and mortality in African Americans with type 1 diabetes. Diabetes Res Clin Pract 2016; 114: 117-25.
[http://dx.doi.org/10.1016/j.diabres.2015.12.014] [PMID: 26806456]
[82]
Heier M, Margeirsdottir HD, Brunborg C, Hanssen KF, Dahl-Jørgensen K, Seljeflot I. Inflammation in childhood type 1 diabetes; influence of glycemic control. Atherosclerosis 2015; 238(1): 33-7.
[http://dx.doi.org/10.1016/j.atherosclerosis.2014.11.018] [PMID: 25437887]
[83]
McEneny J, Daniels J-A, McGowan A, et al. A cross-sectional study demonstrating increased serum amyloid a related inflammation in high-density lipoproteins from subjects with type 1 diabetes mellitus and how this association was augmented by poor glycaemic control. J Diabetes Res 2015; 2015: 351601
[http://dx.doi.org/10.1155/2015/351601] [PMID: 26557720]
[84]
Babar G, Clements M, Dai H, Raghuveer G. Assessment of biomarkers of inflammation and premature atherosclerosis in adolescents with type-1 diabetes mellitus. J Pediatr Endocrinol Metab 2019; 32(2): 109-13.
[http://dx.doi.org/10.1515/jpem-2018-0192] [PMID: 30710485]
[85]
Eiswirth M, Clark E, Diamond M. Low carbohydrate diet and improved glycaemic control in a patient with type one diabetes. Endocrinol Diabetes Metab Case Rep 2018; 2018: 18.
[http://dx.doi.org/10.1530/EDM-18-0002] [PMID: 29576869]
[86]
Mayer-Davis EJ, Laffel LM, Buse JB. Management of type 1 diabetes with a very low-carbohydrate diet: a word of caution. Pediatrics 2018; 142(2): e20181536B
[http://dx.doi.org/10.1542/peds.2018-1536B] [PMID: 30065007]
[87]
Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002; 105(9): 1135-43.
[http://dx.doi.org/10.1161/hc0902.104353] [PMID: 11877368]
[88]
Cronin O, Keohane DM, Molloy MG, Shanahan F. The effect of exercise interventions on inflammatory biomarkers in healthy, physically inactive subjects: a systematic review. QJM 2017; 110(10): 629-37.
[http://dx.doi.org/10.1093/qjmed/hcx091] [PMID: 28472518]
[89]
Karstoft K, Pedersen BK. Exercise and type 2 diabetes: focus on metabolism and inflammation. Immunol Cell Biol 2016; 94(2): 146-50.
[http://dx.doi.org/10.1038/icb.2015.101] [PMID: 26568029]
[90]
Pedersen BK. Anti-inflammatory effects of exercise: role in diabetes and cardiovascular disease. Eur J Clin Invest 2017; 47(8): 600-11.
[http://dx.doi.org/10.1111/eci.12781] [PMID: 28722106]
[91]
Nieman DC, Wentz LM. The compelling link between physical activity and the body’s defense system. J Sport Health Sci 2019; 8(3): 201-17.
[http://dx.doi.org/10.1016/j.jshs.2018.09.009] [PMID: 31193280]
[92]
Trayhurn P, Drevon CA, Eckel J. Secreted proteins from adipose tissue and skeletal muscle - adipokines, myokines and adipose/muscle cross-talk. Arch Physiol Biochem 2011; 117(2): 47-56.
[http://dx.doi.org/10.3109/13813455.2010.535835] [PMID: 21158485]
[93]
Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev 2008; 88(4): 1379-406.
[http://dx.doi.org/10.1152/physrev.90100.2007] [PMID: 18923185]
[94]
Benatti FB, Pedersen BK. Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation. Nat Rev Rheumatol 2015; 11(2): 86-97.
[http://dx.doi.org/10.1038/nrrheum.2014.193] [PMID: 25422002]
[95]
Fischer CP. Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev 2006; 12: 6-33.http://www.ncbi.nlm.nih.gov/pubmed/17201070
[PMID: 17201070]
[96]
Roch-Norlund AE, Bergström J, Castenfors H, Hultman E. Muscle glycogen in patients with diabetes mellitus. Glycogen content before treatment and the effect of insulin. Acta Med Scand 1970; 187(6): 445-53.
[http://dx.doi.org/10.1111/j.0954-6820.1970.tb02969.x] [PMID: 5458175]
[97]
Campbell MD, Walker M, Trenell MI, et al. A low-glycemic index meal and bedtime snack prevents postprandial hyperglycemia and associated rises in inflammatory markers, providing protection from early but not late nocturnal hypoglycemia following evening exercise in type 1 diabetes. Diabetes Care 2014; 37(7): 1845-53.
[http://dx.doi.org/10.2337/dc14-0186] [PMID: 24784832]
[98]
Paterson M, Bell KJ, O’Connell SM, Smart CE, Shafat A, King B. The role of dietary protein and fat in glycaemic control in type 1 diabetes: implications for intensive diabetes management. Curr Diab Rep 2015; 15(9): 61.
[http://dx.doi.org/10.1007/s11892-015-0630-5] [PMID: 26202844]
[99]
American College of Sports Medicine D. Riebe D, Ehrman JK, Liguori G, Magal M. ACSM’s guidelines for exercise testing and prescription. 10th ed. 2018.
[100]
Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep 1985; 100(2): 126-31.
[http://dx.doi.org/10.2307/20056429] [PMID: 3920711]
[101]
Yang J. Enhanced skeletal muscle for effective glucose homeostasis. Prog Mol Biol Transl Sci 2014; 121: 133-63.
[http://dx.doi.org/10.1016/B978-0-12-800101-1.00005-3] [PMID: 24373237]
[102]
Zierath JR, Hawley JA. Skeletal muscle fiber type: influence on contractile and metabolic properties. PLoS Biol 2004; 2(10): e348
[http://dx.doi.org/10.1371/journal.pbio.0020348] [PMID: 15486583]
[103]
Li M, Zhou X, Chen Y, et al. Not all the number of skeletal muscle fibers is determined prenatally. BMC Dev Biol 2015; 15: 42.
[http://dx.doi.org/10.1186/s12861-015-0091-8] [PMID: 26559169]
[104]
Yan X, Zhu M-J, Dodson MV, Du M. Developmental programming of fetal skeletal muscle and adipose tissue development. J Genomics 2013; 1: 29-38.
[http://dx.doi.org/10.7150/jgen.3930] [PMID: 25031653]
[105]
Flann KL, LaStayo PC, McClain DA, Hazel M, Lindstedt SL. Muscle damage and muscle remodeling: no pain, no gain? J Exp Biol 2011; 214(Pt 4): 674-9.
[http://dx.doi.org/10.1242/jeb.050112] [PMID: 21270317]
[106]
Mangine GT, Hoffman JR, Gonzalez AM, et al. The effect of training volume and intensity on improvements in muscular strength and size in resistance-trained men. Physiol Rep 2015; 3(8): e12472
[http://dx.doi.org/10.14814/phy2.12472] [PMID: 26272733]
[107]
Schoenfeld BJ, Contreras B, Krieger J, et al. Resistance training volume enhances muscle hypertrophy but not strength in trained men. Med Sci Sports Exerc 2019; 51(1): 94-103.
[http://dx.doi.org/10.1249/MSS.0000000000001764] [PMID: 30153194]
[108]
Turner D, Luzio S, Kilduff LP, et al. Reductions in resistance exercise-induced hyperglycaemic episodes are associated with circulating interleukin-6 in type 1 diabetes. Diabet Med 2014; 31(8): 1009-13.
[http://dx.doi.org/10.1111/dme.12462] [PMID: 24702172]
[109]
Ballor DL, Becque MD, Katch VL. Metabolic responses during hydraulic resistance exercise. Med Sci Sports Exerc 1987; 19(4): 363-7.
[http://dx.doi.org/10.1249/00005768-198708000-00007] [PMID: 3657485]
[110]
Tanimoto M, Sanada K, Yamamoto K, et al. Effects of whole-body low-intensity resistance training with slow movement and tonic force generation on muscular size and strength in young men. J Strength Cond Res 2008; 22(6): 1926-38.
[http://dx.doi.org/10.1519/JSC.0b013e318185f2b0] [PMID: 18978616]
[111]
Schoenfeld BJ, Aragon AA. How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution. J Int Soc Sports Nutr 2018; 15: 10.
[http://dx.doi.org/10.1186/s12970-018-0215-1]
[112]
Morton RW, Murphy KT, McKellar SR, et al. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med 2018; 52(6): 376-84.
[http://dx.doi.org/10.1136/bjsports-2017-097608] [PMID: 28698222]
[113]
Paterson MA, Smart CEM, Lopez PE, et al. Influence of dietary protein on postprandial blood glucose levels in individuals with Type 1 diabetes mellitus using intensive insulin therapy. Diabet Med 2016; 33(5): 592-8.
[http://dx.doi.org/10.1111/dme.13011] [PMID: 26499756]
[114]
Longland TM, Oikawa SY, Mitchell CJ, Devries MC, Phillips SM. Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial. Am J Clin Nutr 2016; 103(3): 738-46.
[http://dx.doi.org/10.3945/ajcn.115.119339] [PMID: 26817506]
[115]
Cholewa JM, Newmire DE, Zanchi NE. Carbohydrate restriction: Friend or foe of resistance-based exercise performance? Nutrition 2019; 60: 136-46.
[http://dx.doi.org/10.1016/j.nut.2018.09.026] [PMID: 30586657]
[116]
Burke LM, Kiens B, Ivy JL. Carbohydrates and fat for training and recovery. J Sports Sci 2004; 22(1): 15-30.
[http://dx.doi.org/10.1080/0264041031000140527] [PMID: 14971430]
[117]
Poole C, Wilborn C, Taylor L, Kerksick C. The role of post-exercise nutrient administration on muscle protein synthesis and glycogen synthesis. J Sports Sci Med 2010; 9(3): 354-63.
[PMID: 24149627]
[118]
Murphy CH, Hector AJ, Phillips SM. Considerations for protein intake in managing weight loss in athletes. Eur J Sport Sci 2015; 15(1): 21-8.
[http://dx.doi.org/10.1080/17461391.2014.936325] [PMID: 25014731]
[119]
Wolpert HA, Atakov-Castillo A, Smith SA, Steil GM. Dietary fat acutely increases glucose concentrations and insulin requirements in patients with type 1 diabetes: implications for carbohydrate-based bolus dose calculation and intensive diabetes management. Diabetes Care 2013; 36(4): 810-6.
[http://dx.doi.org/10.2337/dc12-0092] [PMID: 23193216]
[120]
van der Hoogt M, van Dyk JC, Dolman RC, Pieters M. Protein and fat meal content increase insulin requirement in children with type 1 diabetes - Role of duration of diabetes. J Clin Transl Endocrinol 2017; 10: 15-21.
[http://dx.doi.org/10.1016/j.jcte.2017.10.002] [PMID: 29204367]
[121]
Bohn B, Herbst A, Pfeifer M, et al. DPV Initiative. Impact of physical activity on glycemic control and prevalence of cardiovascular risk factors in adults with type 1 diabetes: a cross-sectional multicenter study of 18,028 patients. Diabetes Care 2015; 38(8): 1536-43.
[http://dx.doi.org/10.2337/dc15-0030] [PMID: 26015557]
[122]
Spriet LL. New insights into the interaction of carbohydrate and fat metabolism during exercise. Sports Med 2014; 44(Suppl. 1): S87-96.
[http://dx.doi.org/10.1007/s40279-014-0154-1] [PMID: 24791920]
[123]
Cox PJ, Kirk T, Ashmore T, et al. Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell Metab 2016; 24(2): 256-68.
[http://dx.doi.org/10.1016/j.cmet.2016.07.010] [PMID: 27475046]
[124]
Volek JS, Noakes T, Phinney SD. Rethinking fat as a fuel for endurance exercise. Eur J Sport Sci 2015; 15(1): 13-20.
[http://dx.doi.org/10.1080/17461391.2014.959564] [PMID: 25275931]
[125]
McClelland GB. Fat to the fire: the regulation of lipid oxidation with exercise and environmental stress. Comp Biochem Physiol B Biochem Mol Biol 2004; 139(3): 443-60.
[http://dx.doi.org/10.1016/j.cbpc.2004.07.003] [PMID: 15544967]
[126]
Achten J, Jeukendrup AE. Maximal fat oxidation during exercise in trained men. Int J Sports Med 2003; 24(8): 603-8.
[http://dx.doi.org/10.1055/s-2003-43265] [PMID: 14598198]
[127]
Dumke CL, Keck NA, McArthur MC, Corcoran MH. Patients with type 1 diabetes oxidize fat at a greater rate than age- and sex-matched controls. Phys Sportsmed 2013; 41(4): 78-85.
[http://dx.doi.org/10.3810/psm.2013.11.2038] [PMID: 24231599]
[128]
Turton JL, Raab R, Rooney KB. Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review. PLoS One 2018; 13(3): e0194987
[http://dx.doi.org/10.1371/journal.pone.0194987] [PMID: 29596460]
[129]
Granado-Casas M, Alcubierre N, Martín M, et al. Improved adherence to Mediterranean Diet in adults with type 1 diabetes mellitus. Eur J Nutr 2018; 58(6): 1-9.
[http://dx.doi.org/10.1007/s00394-018-1777-z] [PMID: 30019088]
[130]
Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition 2015; 31(1): 1-13.
[http://dx.doi.org/10.1016/j.nut.2014.06.011] [PMID: 25287761]
[131]
Nolan J, Rush A, Kaye J. Glycaemic stability of a cyclist with Type 1 diabetes: 4011 km in 20 days on a ketogenic diet. Diabet Med 2019; 36(11): 1503-7.
[http://dx.doi.org/10.1111/dme.14049] [PMID: 31197870]
[132]
Leow ZZX, Guelfi KJ, Davis EA, Jones TW, Fournier PA. The glycaemic benefits of a very-low-carbohydrate ketogenic diet in adults with Type 1 diabetes mellitus may be opposed by increased hypoglycaemia risk and dyslipidaemia. Diabet Med 2018; 35: 1258-63.
[http://dx.doi.org/10.1111/dme.13663] [PMID: 29737587]
[133]
McClean AM, Montorio L, McLaughlin D, McGovern S, Flanagan N. Can a ketogenic diet be safely used to improve glycaemic control in a child with type 1 diabetes? Arch Dis Child 2019; 104(5): 501-4.
[http://dx.doi.org/10.1136/archdischild-2018-314973] [PMID: 30470684]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version447msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[18:01:44] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[18:01:45] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[18:01:45] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (91.27ms)time
  • Application (356ms)time
  • 1 x Application (79.6%)
    356ms
    1 x Booting (20.4%)
    91.27ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    37 statements were executed, 4 of which were duplicates, 33 unique. Show only duplicated282ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('316582179','',1,1739988104,1739988104) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739988104
      1.09msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('316582179','/article/103551',1,1739988104,1739988104)
      970μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316582179 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316582179) limit 1
      12msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316582179
      • 1: 316582179
      • 2: 316582179
      • 3: 316582179
      • 4: 316582179
      • 5: 316582179
      • 6: 316582179
      • 7: 316582179
      • 8: 316582179
      • 9: 316582179
      • 10: 316582179
      • 11: 316582179
      • 12: 316582179
      • 13: 316582179
      • 14: 316582179
      • 15: 316582179
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=103551
      660μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 29 limit 1
      820μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 29
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and sj.journal_id!=29 group by `j`.`nid`) as `aggregate_table`
      1.02msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and sj.journal_id!=29 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      840μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.06msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      990μsalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '103551'
      1.97msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 103551
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '103551'
      4.77msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 103551
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '103551' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.49msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 103551
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      280μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      480μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 29 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      47.26msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 29 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      49.03msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 29 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      38.43msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 103551 limit 1
      1.59msalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 103551
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 103551 and content_type = 'article' order by status desc limit 1
      1.86msalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 283 and cd.sub_disease_id = 301 and content_id!=103551 and cd.content_type = 'article' order by rand() limit 20
      99.36msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 178167 limit 1
      360μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 178167
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      290μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CPD' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      380μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CPD
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '103551' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      400μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '9810' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      350μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '2790' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      340μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988105 and j.to_date >= 1739988105 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2790) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988105 and j.to_date >= 1739988105 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2790) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988105 and j.to_date >= 1739988105 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2790)
      4.61msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988105 and j.to_date >= 1739988105 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9810) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988105 and j.to_date >= 1739988105 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9810) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988105 and j.to_date >= 1739988105 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9810)
      640μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988105 and j.to_date >= 1739988105 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 103551) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988105 and j.to_date >= 1739988105 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 103551) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316582179 and j.to_ip >=316582179 )) and ((j.from_date <= 1739988105 and j.to_date >= 1739988105 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 103551)
      620μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '946' and is_uploaded = 1 and issue_id = 9810 order by cast(first_page as SIGNED) desc limit 1
      550μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 946
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '957' and is_uploaded = 1 and issue_id = 9810 order by cast(first_page as SIGNED) asc limit 1
      480μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 957
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      200μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      220μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 103551 limit 1
      2.48msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 103551
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 29 and `b`.`banner_from_date` <= 1739988105 and `b`.`banner_to_date` >= 1739988105 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.16msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 29
      • 3: 1739988105
      • 4: 1739988105
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 29 and `b`.`banner_from_date` <= 1739988105 and `b`.`banner_to_date` >= 1739988105 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.65msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 29
      • 3: 1739988105
      • 4: 1739988105
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='c892d66e03bc5ee7a5ec1d151549075d'
      250μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        wawNvhlCaCZkALuw9K7nuSgtBps5qqCUbo4uxZlQ
        uc_cart_id
        c892d66e03bc5ee7a5ec1d151549075d
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/103551" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/103551
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6Ilo5ZUJNNkVWNVVuaWxNRm5JSGZSVHc9PSIsInZhbHVlIjoiTVVablJQMEVaVEkrRlpqTXYzMm03MXRJVHNYbHRsWjZoazNKQmpmVTdrVT0iLCJtYWMiOiI5MmIwMzM2MDk2NTM4OWIzZDc2MGI1MTQwMDg5YTI0NWIwMjlhZjhmODIyODQ3YzZlZTUxMTFlMGQ4MDE2Mjg4IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6Ilo5ZUJNNkVWNVVuaWxNRm5JSGZSVHc9PSIsInZhbHVlIjoiTVVablJQMEVaVEkrRlpqTXYzMm03MXRJVHNYbHRsWjZoazNKQmpmVTdrVT0iLCJtYWMiOiI5MmIwMzM2MDk2NTM4" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Wed, 19 Feb 2025 18:01:45 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InhxcjdiUVBFdlhWUjl1VzM4UXZ0eFE9PSIsInZhbHVlIjoiK0FyVWdnY2syMUxYUlM4cmJ5OEQralVCVnNhRFc4QmRUT3dxN3Z0bzNSaEg3WWpqQ2tsUFJGL1kzT1hHV0dVcEg0dnlJcytYME44dk9sc1RZNGtQa09NQUN5c2Y3T2VXcWNqM0ZKWGRLUmtrbk9xNUU3cDVuRDYyVVlxcjFsMUUiLCJtYWMiOiI4Y2U5Yzc1MWYzNjg2NzliMGMwZGEzZWJkNGRhOGMwYjdjOWQ1YzEyNzBhYTIxYjViNGFhNDI1YWFkOGE5YjgyIiwidGFnIjoiIn0%3D; expires=Sat, 22 Feb 2025 06:01:45 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6InhxcjdiUVBFdlhWUjl1VzM4UXZ0eFE9PSIsInZhbHVlIjoiK0FyVWdnY2syMUxYUlM4cmJ5OEQralVCVnNhRFc4QmRUT3dxN3Z0bzNSaEg3WWpqQ2tsUFJGL1kzT1hHV0dVcEg0dnlJc" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlJwamx0T210emJ1dWJna3B0dG5FWXc9PSIsInZhbHVlIjoiTG0wQ09abWZRcS9ZVUoyQXpvdzNubzZTNTA0YTJzSXlDZXc0Q25HaVp6WkltdXlqNENUcEdVM2VRWWRuL1dYelZEQ1B4REViYjU2RUxPaGpkSEU5a1piYkdOa1lPK3Q4S0NvWVhSTHczUm5JYVQxQUJWMWp5bVVWckJRb0RkVXQiLCJtYWMiOiI3YzJhNTA1YjRlMThhZjg4MWQxMTcyY2JkN2JmNGYxNmIyZjI5NThiMGFmMGE5YWZjMTEzZWU5YWZiMDViZjk0IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IlJwamx0T210emJ1dWJna3B0dG5FWXc9PSIsInZhbHVlIjoiTG0wQ09abWZRcS9ZVUoyQXpvdzNubzZTNTA0YTJzSXlDZXc0Q25HaVp6WkltdXlqNENUcEdVM2V" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InhxcjdiUVBFdlhWUjl1VzM4UXZ0eFE9PSIsInZhbHVlIjoiK0FyVWdnY2syMUxYUlM4cmJ5OEQralVCVnNhRFc4QmRUT3dxN3Z0bzNSaEg3WWpqQ2tsUFJGL1kzT1hHV0dVcEg0dnlJcytYME44dk9sc1RZNGtQa09NQUN5c2Y3T2VXcWNqM0ZKWGRLUmtrbk9xNUU3cDVuRDYyVVlxcjFsMUUiLCJtYWMiOiI4Y2U5Yzc1MWYzNjg2NzliMGMwZGEzZWJkNGRhOGMwYjdjOWQ1YzEyNzBhYTIxYjViNGFhNDI1YWFkOGE5YjgyIiwidGFnIjoiIn0%3D; expires=Sat, 22-Feb-2025 06:01:45 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6InhxcjdiUVBFdlhWUjl1VzM4UXZ0eFE9PSIsInZhbHVlIjoiK0FyVWdnY2syMUxYUlM4cmJ5OEQralVCVnNhRFc4QmRUT3dxN3Z0bzNSaEg3WWpqQ2tsUFJGL1kzT1hHV0dVcEg0dnlJc" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlJwamx0T210emJ1dWJna3B0dG5FWXc9PSIsInZhbHVlIjoiTG0wQ09abWZRcS9ZVUoyQXpvdzNubzZTNTA0YTJzSXlDZXc0Q25HaVp6WkltdXlqNENUcEdVM2VRWWRuL1dYelZEQ1B4REViYjU2RUxPaGpkSEU5a1piYkdOa1lPK3Q4S0NvWVhSTHczUm5JYVQxQUJWMWp5bVVWckJRb0RkVXQiLCJtYWMiOiI3YzJhNTA1YjRlMThhZjg4MWQxMTcyY2JkN2JmNGYxNmIyZjI5NThiMGFmMGE5YWZjMTEzZWU5YWZiMDViZjk0IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IlJwamx0T210emJ1dWJna3B0dG5FWXc9PSIsInZhbHVlIjoiTG0wQ09abWZRcS9ZVUoyQXpvdzNubzZTNTA0YTJzSXlDZXc0Q25HaVp6WkltdXlqNENUcEdVM2V" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "wawNvhlCaCZkALuw9K7nuSgtBps5qqCUbo4uxZlQ" "uc_cart_id" => "c892d66e03bc5ee7a5ec1d151549075d" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/103551" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 18:01:45GET/article/103551314371