Remissione del diabete tipo 2 Terapia Medica Dr

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

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

Therapeutic implications of the pathogenesis of type 2 diabetes

ADA-EASD Position Statement: Management of Hyperglycemia in T 2 DM • Glycemic targets - Hb. A 1 c < 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: Ø Tighter targets (6. 0 - 6. 5%) - younger, healthier + Ø Looser targets (7. 5 - 8. 0% ) - older, comorbidities, hypoglycemia prone, etc. - Avoidance of hypoglycemia PG = plasma glucose

Therapeutic implications of the pathogenesis of type 2 diabetes e thes in h t i form in w Beg s if met ted ica on opti ntraind co al l du y a i t i in ap ider on ther s n Co inati % b c >9 1 m A o c n whe tial i n i r side erapy n o C th -12% n i l u ins 1 c >10 n. A whe Diabetes Care 2012, Diabetologia 2012

[. . ] 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 Diab Care, vol 32 n 11 November 2009

Hb. A 1 c < 6. 5% Glycemia 100 -125 mg/dl Hb. A 1 c < 6. 0% Glycemia < 100 mg/dl Buse JB et al. Diab Care 2009

Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes 6. 5 Mingrone G NEJM 2012

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

Is it possible to have Remission of Type 2 Diabetes with Medical Therapy? Retnakaran R, Zinman B, Diabetes, Obesity and Metabolism, 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 >1 year Chen A, Diabetes Care 2012

Is it possible to have Remission of Type 2 Diabetes with Medical Therapy? b-cell Function 188 patients 68. 9% 60. 6% 49. 5% Liu J End Jap 2012

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

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

Weng J, Lancet 2008

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

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.