GLITAZONES & FRACTURE RISK
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GLITAZONES & FRACTURE RISK
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GLITAZONES & FRACTURE RISK
- 1. GLITAZONES & THEIR FRACTURE RISK Prof. P.K. Jain MD,MNAMS Professor & Head, Department of Medicine, M.L.B. Medical College, Jhansi, UP
- 5. MECHANISM OF ACTION OF GLITAZONES
- 9. Thiazolidinediones Reduce insulin resistance in muscle, adipose tissue and liver Adapted from Saltiel 1996, Jones 1999 Decrease circulating levels of insulin Decrease gluconeogenesis in liver Decrease blood glucose levels Adipose tissue Muscle Liver Blood glucose Pancreas
- 13. REMEMBER WHERE GLITAZONES WENT WRONG!!
- 15. Bone health and diabetes
- 17. Copyright ©2007 Canadian Medical Association or its licensors Meymeh, R. H. et al. CMAJ 2007;177:723-724
- 23. J Bone Miner Metab 17:119–124, 1999
- 30. June , 2007 A bad month altogether for glitazones
- 33. ADOPT Analysis Shows Rosiglitazone Increases Risk of Fracture in Women June 29, 2007 (Chicago) -- "In ADOPT, the increased risk of bone fractures in women with type 2 diabetes was accentuated with rosiglitazone," said during a late-breaking clinical-trials session at the American Diabetes Association 2007 Scientific Sessions.
- 46. Kaplan Meier estimates of cumulative incidence of fractures at 5 yrs. In All Patients.
- 47. Kaplan Meier estimates of cumulative incidence of fractures at 5 yrs. In MEN
- 48. Kaplan Meier estimates of cumulative incidence of fractures at 5 yrs. In WOMEN
- 61. With Glitazones-Do Routine BMD
Editor's Notes
- The thiazolidinediones activate the nuclear receptor peroxisomal proliferator activated receptor gamma (PPAR-gamma). This receptor is found in high levels in adipose tissue and also in muscle and the liver. It regulates the transcription of a number of genes responsible for preadipocyte differentiation and insulin-mediated uptake of glucose by peripheral tissues. 1 The thiazolidinediones act to enhance the action of insulin but do not stimulate insulin secretion; 2 in fact, circulating insulin levels are decreased. 2,3 The insulin-sensitising effect is brought about by increasing insulin-regulated glucose uptake in adipose and muscle tissue. In addition, hepatic glucose production is suppressed. 4 Thiazolidinediones also reduce circulating free fatty acid levels (FFAs) by reducing the lipolytic effects of tumour necrosis factor alpha (TNF-alpha). 5 Rosiglitazone is a member of the thiazolidinedione class. 1 References 1. Balfour JAB, Plosker GL. Rosiglitazone. Drugs 1999; 57 : 921–30. 2. Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type 2 diabetes. Diabetes 1996; 45 : 1661–9. 3. Jones NP, Charbonnel B, Lonnqvist F et al . Rosiglitazone reduces plasma insulin and its precursors while decreasing glycaemia in type 2 diabetics. Diabetologia 1999; 42 (Suppl.): abs. 859 and poster. 4. Reasner CA. Promising new approaches. Diab Obes Metab 1999; 1 (Suppl.1): S41–S48. 5. Souza SC, Yamamoto MT, Franciosa MD et al . BRL 49653 blocks the lipolytic actions of tumor necrosis factor alpha (TNF-alpha). Diabetes 1998; 47 : 691–5.