Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Universit Federico II.

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Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Universit Federico II Occhio e Diabete Napoli, 17-18 aprile 2015 Slide 2 Slide 3 Type 2 diabetes is associated with serious complications at time of diagnosis The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2001; 24 (Suppl. 1): S5-S20 Retinopathy, glaucoma or cataracts Nephropathy Neuropathy Microvascular Macrovascular Cerebrovascular disease Coronary heart disease Peripheral vascular disease Slide 4 Hyperglycemia-Induced Tissue Damage: General Features Diabetic tissue damage Genetic determinants of individual susceptibility Repeated acute changes in cellular metabolism Cumulative long-term changes in stable macromolecules Independent accelerating factors (eg, hypertension, dyslipidemia) Hyperglycemia Brownlee M. Diabetes. 2005;54:1615-1625. Slide 5 Microvascular Complications of Diabetes NephropathyRetinopathyNeuropathy Slide 6 Prevalence of Diabetic Retinopathy *Severe NPDR, PDR, or clinically significant macular edema. NPDR, nonproliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy; T2DM, type 2 diabetes mellitus. CDC. National diabetes fact sheet, 2011. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Zhang X, et al. JAMA. 2010;304:649-656. NHANES 2005-2008 Adults Age 40 Years (N=1006) Diabetic Retinopathy Is the Leading Cause of Adult Blindness in the United States Slide 7 Disease Duration (yrs) 1 5 1 - 15 Retinopathy NO very mild-to-moderate Urinary Albumin Excretion (mg/day) < 40 < 200 Slide 8 DCCT, NEJM 1993 Hyperglycemia and Retinopathy in T1D Slide 9 Primary prevention group Secondary prevention group -76% -54% Seven field stereoscopic fundus photography Early Treatment Diabetic Retinopathy Study grading DCCT, NEJM 1993 Hyperglycemia and Retinopathy in T1D Slide 10 Hyperglycemia and Retinopathy in T1D DCCT & EDIC, NEJM 2000 & Arch Intern Med 2009 Slide 11 Hyperglycemia and Retinopathy in T1D Slide 12 DCCT, Diabetes Control and Complications Trial. 1. Adapted from Skyler JS. Endocrinol Metab Clin North Am. 1996;25:243-254. 2. DCCT. N Engl J Med. 1993;329:977-986. 3. DCCT. Diabetes. 1995;44:968-983. Relative Risk HbA1 C (%) 15 13 11 9 7 5 3 1 6789101112 HbA1 C and Relative Risk of Microvascular Complications Retinopathy Nephropathy Neuropathy Microalbuminuria 20 DCCT, NEJM 1993 Slide 13 DCCT and EDIC Findings Intensive treatment reduced the risks of retinopathy, nephropathy, and neuropathy by 35% to 90% compared with conventional treatment Absolute risks of retinopathy and nephropathy were proportional to the A1C Intensive treatment was most effective when begun early, before complications were detectable Risk reductions achieved at a median A1C 7.3% for intensive treatment (vs 9.1% for conventional) Benefits of 6.5 years of intensive treatment extended well beyond the period of most intensive implementation (metabolic memory) DCCT/EDIC Research Group. JAMA. 2002;15;287:2563-2569. Intensive treatment should be started as soon as is safely possible after the onset of T1DM and maintained thereafter Slide 14 UKPDS, Lancet 1998 Slide 15 Hyperglycemia and Retinopathy in T2D Slide 16 UKPDS, Lancet 1998 Hyperglycemia and Retinopathy in T2D Slide 17 Slide 18 Reducing A1C Reduces Retinopathy Progression in T2DM *Intensive vs standard glucose control. UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-853. Ismail-Beigi F, et al. Lancet. 2010;376:419-430. Chew EY, et al. N Engl J Med. 2010;363:233-244. UKPDSACCORD A1C reduction (%)0.91.3 Retinopathy risk reduction (%)* 291733 Retinopathy onset (P=0.003) Retinopathy progression (P=0.017) Retinopathy progression (P=0.003) Slide 19 Hemmingsen B et al. Br Med J 2011 Hyperglycemia and Retinopathy Slide 20 Boussageon R et al. Br Med J 2011 Hyperglycemia and Retinopathy: the sooner the better Slide 21 RACCOMANDAZIONI Raccomandazioni generali Ottimizzare il compenso glicemico riduce il rischio e la progressione della retinopatia. (Livello della prova I, Forza della raccomandazione A) Slide 22 Predictors of Poor Glycemic Control Younger age Longer diabetes duration WeightSlide 23 Primary prevention group Secondary prevention group -76% -54% Seven field stereoscopic fundus photography Early Treatment Diabetic Retinopathy Study grading DCCT, NEJM 1993 Hyperglycemia and Retinopathy in T1D Slide 24 Slide 25 Slide 26 Glucose Variability and Health Outcomes: Direct and Indirect Pathways Irvine AA, et al. Health Psychol. 1992;11:135-138; Thompson CJ, et al. Diabetes Care. 1996;19:876-879; Reach G. Diabetes Technol Ther. 2008;10:69-80. Glucose variability Reluctance to intensify therapy High A1C Complications Morbidity Mortality Complications Morbidity Mortality Quality of life Fear of hypoglycemia Severe hypoglycemia Controversial Slide 27 RACCOMANDAZIONI Raccomandazioni generali Ottimizzare il compenso glicemico riduce il rischio e la progressione della retinopatia. (Livello della prova I, Forza della raccomandazione A) Slide 28 Diabetic Retinopathy Management Lesion TypeManagement Recommendation Background or nonproliferative retinopathy Optimal glucose and blood pressure control Macular edema Optimal glucose and blood pressure control Ranibizumab injection therapy Focused laser photocoagulation guided by fluorescein angiography Preproliferative retinopathy Optimal glucose and blood pressure control Panretinal scatter laser photocoagulation Proliferative retinopathy Optimal glucose and blood pressure control Panretinal scatter laser photocoagulation Vitrectomy for patients with persistent vitreous hemorrhage or significant vitreous scarring and debris Goal: detect clinically significant retinopathy before vision is threatened Annual dilated eye examination by experienced ophthalmologist, starting at diagnosis for all T2DM patients Handelsman Y, et al. Endocr Pract. 2011;17(suppl 2):1-53. Slide 29 Standards of Medical Care in Diabetes - 2015 Slide 30 Slide 31

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