1. Remissione del diabete tipo 2: Terapia Medica Dr. Monica Nannipieri Dipartimento di Medicina Clinica e Sperimentale Università di Pisa

2. Adapted from De Fronzo RA, Diabetes 2009 Increased Glucagon Secretion Neurotransmitter Dysfunction Decreased Incretin Effect Increased HGP Decreased Glucose Uptake Increased Glucose Reabsorption Increased Lipolysis Hyperglycemia Decreased Insulin Secretion Islet- cell 1.Effective treatment of type 2 diabetes requires multiple drugs used in combination to correct multiple pathophysiological defects 2.Treatment should be based on known pathogenic abnormalities and not simply on reduction of HbA1C 3.Therapy must be started early in the natural history of type 2 diabetes to prevent progressive beta-cell failure Therapeutic implications of the pathogenesis of type 2 diabetes

5. ADA-EASD Position Statement: Management of Hyperglycemia in T2DM Glycemic targets - HbA1c < 7.0% (mean PG  150-160 mg/dl [8.3-8.9 mmol/l ]) - Pre-prandial PG <130 mg/dl (7.2 mmol/l ) - Post-prandial PG <180 mg/dl (10.0 mmol/l ) - Individualization is key:  Tighter targets (6.0 - 6.5%) - younger, healthier  Looser targets (7.5 - 8.0% + ) - older, comorbidities, hypoglycemia prone, etc. - Avoidance of hypoglycemia PG = plasma glucose

6. Diabetes Care 2012, Diabetologia 2012 Therapeutic implications of the pathogenesis of type 2 diabetes Consider initial insulin therapy when A1c >10-12% Begin with these options if metformin contraindicated Consider initial dual combination therapy when A1c >9%

7. Diab Care, vol 32 n 11 November 2009 [..] For a chronic illness such as diabetes, it may be more accurate to use the term remission than cure. Current or potential future therapies for type 1 and type 2 diabetes will likely always leave patients at risk for relapse, given underlying pathophysiologic abnormalities and/or genetic predisposition The authors agreed upon the following definitions, which are the same for type 1 and type 2 diabetes: Remission is defined as achieving glycemia below the diabetic range in the absence of active pharmacologic (anti-hyperglycemic medications, immunosuppressive medications) or surgical (ongoing procedures such as repeated replacement of endoluminal devices) therapy

8. Buse JB et al. Diab Care 2009 HbA1c < 6.5% Glycemia 100-125 mg/dl HbA1c < 6.0% Glycemia < 100 mg/dl

9. Mingrone G NEJM 2012 Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes 6.5

10. DIABETES REMISSION AFTER WEIGHT LOSS INTERVENTION Gregg EW JAMA 2012 Is it possible to have Remission of Type 2 Diabetes with Medical Therapy? Randomized control trial, 4 years follow-up 4503 pts

11. Retnakaran R, Zinman B, Diabetes, Obesity and Metabolism, 2012. Is it possible to have Remission of Type 2 Diabetes with Medical Therapy?

12. Chen A, Diabetes Care 2012 Is it possible to have Remission of Type 2 Diabetes with Medical Therapy? 118 pts in CSII for 2 wks, 53 non remission 65 in remission for >1year

13. Liu J End Jap 2012 68.9% 60.6% 49.5% Is it possible to have Remission of Type 2 Diabetes with Medical Therapy?  -cell Function 188 patients

14. Liu J End Jap 2012 Is it possible to have Remission of Type 2 Diabetes with Medical Therapy?

15. Wen XU, Chin Med J 2009 Is it possible to have Remission of Type 2 Diabetes with Medical Therapy? 84 patients 42 patients

16. Weng J, Lancet 2008

17. Retnakaran R, Zinman B, Diabetes, Obesity and Metabolism, 2012. Predictors of successful sustained euglycemia Is it possible to have Remission of Type 2 Diabetes with Medical Therapy? When?

18. SUMMARY  The effects of medical treatment on diabetes are related to improvement or restoration of: a.insulin sensitivity (life style, weight loss);  -cell function (hormonal factors and reduction of glucotoxicity and lipotoxicity).  Rate of success of medical treatment in terms of diabetes remission may depend on the extent of  -cell dysfunction/loss at time of treatment and, hence, could be lower for: a.longer diabetes duration; b.less BMI.