Appraisal and Reappraisalof Diabetes in 2013Karthik BalachandranDepartment of Endocrinology
AppraisalReappraisal
• nonacetylated prodrug of salicylate• Obesity chronic inflammation role of anti-inflammatory agents• Therapeutic doses ...
•Inhibition of NF-k•Inhibition of cellular kinases•Upregulation of the heat shock response•Increases in circulating insuli...
• Cost• Low incidence of hypoglycemia• low incidence of GI side effects (it is a prodrug and does not dissociate inacid pH...
• Anakinra- improves cell function1• Etanercept – failed to improve insulin sensitivity in patients with metabolicsyndrome...
• Used for metabolic syndrome/ type 2 DM11 HSD 1• Cortisone cortisol11 HSD 2
• Thiazolidinediones• Fibrates inhibit11 HSD1Adamantyltriazoles, arylsulfonamidothiazoles, anilinothiazolones-compounds cu...
• Acts as a glucose sensor• Rate-controlling enzyme for hepatic glucose clearance and glycogensynthesis• Present in pancre...
• First published in nature in 2003• Over 100 patents filed and granted since then• Piragliatin- went to phase 2 trials – ...
•TAK-875•Stimulates glucose dependent insulin secretion•Type of improved sulfonylurea•Combination use of a DPP-4 inhibitor...
Two alternative hypotheses on the mechanisms behind lipid-induced insulin resistance and β-cell compensation.Alquier T , a...
• Exubera-marketed in 2006 and discontinued in September 2007 due to poorsales by Pfizer• Afrezza*- ultrarapid acting meal...
• Formulation of GLP-1 onTechnosphere® particles –inhaled• Escapes DPP4 degradation• Does not produce the nausea and vomit...
NewerTechnology
•Devices used for glucose monitoring•Insulin delivery devices
Surgical options
• Consider in DM with BMI> 35• Can be considered for Asians at lower BMI cut offs(IDF positionstatement on bariatric surge...
• 1. PREDOMINANTLY RESTRICTIVE PROCEDURES• 2. PREDOMINANTLY MALABSORBTIVE PROCEDURES• 3. MIXED OR COMBINATION PROCEDURES
RESTRICTIVE PROCEDURES• Creating a small gastric pouch & a degree of outlet obstructionleading to delayed gastric emptying...
Malabsorption is achieved by creating a short gut syndrome and/or byaccomplishing distal mixing of bile and pancreatic jui...
1.GASTRIC BYPASS ROUX-EN-Y ( RYGBP)2.SLEEVE GASTRECTOMY WITH DUODENAL SWITCH3.IMPLANTABLE GASTRIC STIMULATION
• Poorly controlled type 1 DM with diabetic nephropathy may be an indication• Not standardized• Experience poor in many ce...
Newer Approaches
• Newly discovered hormone – Betatrophin• Can be injected yearly or monthly• Shown promising results in miceYi P, Park J-S...
• Using AAV (adeno associated virus vectors) transfection of skeletal musclewith insulin and glucokinase gene• Has been do...
• DiaPep277• Synthetic peptide of 24 amino acids derived from the sequence of thehuman heat shock protein 60 (Hsp60)• Immu...
•Three approaches• Medical equipment•Bioengineering• Gene therapy
Bioengineering approachPrincipleImplant implant bioengineeriedtissue containing islet cells
• Autologous bone marrow derived stem celltransplantation (ABMSCT)• Significant decrease in insulin requirement and glucag...
Strategies to obtain β cells from organ-specific stem or progenitor cellsAguayo-Mazzucato, C. & Bonner-Weir, S. (2010) Ste...
Mouse embryonic stem cells
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management
Upcoming SlideShare
Loading in …5
×

Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management

658 views

Published on

A summary of recent advances and a look into the possible future directions in research and patient care in diabetes

Published in: Health & Medicine
0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
658
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
0
Comments
0
Likes
2
Embeds 0
No embeds

No notes for slide

Appraisal and reappraisal of d iabetes in 2013-Advances in Diabetes Management

  1. 1. Appraisal and Reappraisalof Diabetes in 2013Karthik BalachandranDepartment of Endocrinology
  2. 2. AppraisalReappraisal
  3. 3. • nonacetylated prodrug of salicylate• Obesity chronic inflammation role of anti-inflammatory agents• Therapeutic doses of upto 4 g/dayGoldfine AB, FonsecaV, Jablonski KA, Pyle L, Staten MA, Shoelson SE.The effects of salsalate on glycemiccontrol in patients with type 2 diabetes: a randomized trial. Annals of internal medicine. 2010;152(6):346–57.
  4. 4. •Inhibition of NF-k•Inhibition of cellular kinases•Upregulation of the heat shock response•Increases in circulating insulin concentrations
  5. 5. • Cost• Low incidence of hypoglycemia• low incidence of GI side effects (it is a prodrug and does not dissociate inacid pH of the stomach)
  6. 6. • Anakinra- improves cell function1• Etanercept – failed to improve insulin sensitivity in patients with metabolicsyndrome2• Inflammasome activation – field of active research31: Larsen CM, Faulenbach M, Vaag A, Vølund A, Ehses JA, Seifert B, Mandrup-Poulsen T, DonathMY. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007 Apr12;356(15):1517-262. Bernstein LE, Berry J, Kim S, Canavan B, Grinspoon SK. Effects of etanercept in patients withthe metabolic syndrome. Archives of internal medicine. 2006;166(8):902–8..3. Grant, Ryan W., and Vishwa D. Dixit. "Mechanisms of disease: inflammasome activation and thedevelopment of type 2 diabetes." Frontiers in Immunology 4 (2013).
  7. 7. • Used for metabolic syndrome/ type 2 DM11 HSD 1• Cortisone cortisol11 HSD 2
  8. 8. • Thiazolidinediones• Fibrates inhibit11 HSD1Adamantyltriazoles, arylsulfonamidothiazoles, anilinothiazolones-compounds currently under investigation
  9. 9. • Acts as a glucose sensor• Rate-controlling enzyme for hepatic glucose clearance and glycogensynthesis• Present in pancreas and liver• Hepatic glucokinase entirely insulin dependent• Inactivating mutation results in MODY 2
  10. 10. • First published in nature in 2003• Over 100 patents filed and granted since then• Piragliatin- went to phase 2 trials – but discontinued• Primary impact is on hepatic glucokinase- hence mainly postprandial glucosereduction
  11. 11. •TAK-875•Stimulates glucose dependent insulin secretion•Type of improved sulfonylurea•Combination use of a DPP-4 inhibitor andTAK-875 -interestingAlquier,Thierry, andVincent Poitout. "GPR40: good cop, bad cop?." Diabetes58.5 (2009):1035-1036.
  12. 12. Two alternative hypotheses on the mechanisms behind lipid-induced insulin resistance and β-cell compensation.Alquier T , and Poitout V Diabetes 2009;58:1035-1036Copyright © 2011 American Diabetes Asociation, Inc.
  13. 13. • Exubera-marketed in 2006 and discontinued in September 2007 due to poorsales by Pfizer• Afrezza*- ultrarapid acting meal time insulin (MannKind Corp)Rosenstock J, Lorger DL. Gnudi L, et. al. Prandial inhaled insulin plus basal insulinglargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre randomizedtrial Lancet 2010; 375: 2244-2253.
  14. 14. • Formulation of GLP-1 onTechnosphere® particles –inhaled• Escapes DPP4 degradation• Does not produce the nausea and vomiting characteristic of GLP-1analogues
  15. 15. NewerTechnology
  16. 16. •Devices used for glucose monitoring•Insulin delivery devices
  17. 17. Surgical options
  18. 18. • Consider in DM with BMI> 35• Can be considered for Asians at lower BMI cut offs(IDF positionstatement on bariatric surgery in DM- BMI 27.5 to 32.5)• An Australian report* recommends surgery be considered ifadolescents have BMI >40 , or >35 with severe co-morbidities,are 15 years or over & can provide informed consent*Baur LA & Fitzgerald DA. Recommendations for bariatric surgery in adolescents inAustralia and New Zealand. J Paediatr Child Health 46, 704-707 (2010).
  19. 19. • 1. PREDOMINANTLY RESTRICTIVE PROCEDURES• 2. PREDOMINANTLY MALABSORBTIVE PROCEDURES• 3. MIXED OR COMBINATION PROCEDURES
  20. 20. RESTRICTIVE PROCEDURES• Creating a small gastric pouch & a degree of outlet obstructionleading to delayed gastric emptying• 1.VERTICAL BANDED GASTROPLASTY• 2.ADJUSTABLE GASTRIC BANDING (LAGB )• 3. SLEEVE GASTRECTOMY• 4.GASTRIC PLICATION• 5. INTRA GASTRIC BALLOON (GASTRIC BALLOON)
  21. 21. Malabsorption is achieved by creating a short gut syndrome and/or byaccomplishing distal mixing of bile and pancreatic juice with ingestednutrients thereby reducing absorption.NOT RECOMMENDED1. BILIOPANCREATIC DIVERSION2. THE JEJUNAL-ILEAL BYPASS3. ENDOLUMINAL SLEEVE
  22. 22. 1.GASTRIC BYPASS ROUX-EN-Y ( RYGBP)2.SLEEVE GASTRECTOMY WITH DUODENAL SWITCH3.IMPLANTABLE GASTRIC STIMULATION
  23. 23. • Poorly controlled type 1 DM with diabetic nephropathy may be an indication• Not standardized• Experience poor in many centers
  24. 24. Newer Approaches
  25. 25. • Newly discovered hormone – Betatrophin• Can be injected yearly or monthly• Shown promising results in miceYi P, Park J-S, Melton DA. Betatrophin: A Hormone that Controls Pancreatic β CellProliferation. Cell. 2013;153(4):747–58.
  26. 26. • Using AAV (adeno associated virus vectors) transfection of skeletal musclewith insulin and glucokinase gene• Has been done successfully in dogsCallejas D, Mann CJ, Ayuso E, Lage R, Grifoll I, Roca C, Andaluz A, Ruiz-de Gopegui R, MontanéJ, Muñoz S, FerreT, HaurigotV, Zhou S, Ruberte J, Mingozzi F, High KA, Garcia F, Bosch F.Treatment of diabetes and long-term survival after insulin and glucokinase gene therapy.Diabetes. 2013;62(5):1718–29.O’BrienT. Gene therapy for type 1 diabetes moves a step closer to reality. Diabetes.2013;62(5):1396–7.
  27. 27. • DiaPep277• Synthetic peptide of 24 amino acids derived from the sequence of thehuman heat shock protein 60 (Hsp60)• Immunomodulator preventing cell destructionD.Tuccinardi, E. Fioriti, S. Manfrini, E. DAmico, and P. Pozzilli. "DiaPep277 peptide therapy in thecontext of other immune intervention trials in type 1 diabetes." Expert Opin BiolTher. 2011 JulyV. A. L. Huurman, P.E. van der Meide, G. Duinkerken, S. Willemen, I.R. Cohen, D. Elias, and B.O. Roep.“Immunological efficacy of heat shock protein 60 peptide DiaPep277TM therapy in clinical type 1diabetes.” Clin Exp Immunol. 2008 June;152(3):488-497
  28. 28. •Three approaches• Medical equipment•Bioengineering• Gene therapy
  29. 29. Bioengineering approachPrincipleImplant implant bioengineeriedtissue containing islet cells
  30. 30. • Autologous bone marrow derived stem celltransplantation (ABMSCT)• Significant decrease in insulin requirement and glucagon stimulated Cpeptide levels shown*Bhansali A, A P, Walia R, Bhansali S, Gupta V, Jain A, Sachdeva N, Sharma RR, Marwaha N, Khandelwal N.Efficacy and Safety of Autologous Bone Marrow Derived Stem Cell Transplantation in patients with Type 2 Diabetes mellitus: A randomizedplacebo-controlled study.Cell Transplant. 2013 Apr 2
  31. 31. Strategies to obtain β cells from organ-specific stem or progenitor cellsAguayo-Mazzucato, C. & Bonner-Weir, S. (2010) Stem cell therapy for type 1 diabetes mellitusNat. Rev. Endocrinol. doi:10.1038/nrendo.2009.274Permission obtained from Macmillan Publishers Ltd © Bonner-Weir S. &Weir G. C.Nature Biotechnology 23, 857–861 (2005)
  32. 32. Mouse embryonic stem cells

×