![Page 1: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/1.jpg)
Impatto della terapia ipoglicemizzante sulla retinopatia diabetica
Raffaele NapoliDipartimento di Scienze Mediche Traslazionali
Università Federico II
Occhio e DiabeteNapoli, 17-18 aprile 2015
![Page 2: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/2.jpg)
![Page 3: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/3.jpg)
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
![Page 4: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/4.jpg)
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.
![Page 5: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/5.jpg)
Microvascular Complications of Diabetes
Nephropathy Retinopathy Neuropathy
![Page 6: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/6.jpg)
Vision-threaten-ing*; 4.4%
NPDR; 24.1%
None; 71.5%
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 2005-2008Adults Age ≥40 Years (N=1006)
Diabetic Retinopathy Is the Leading Cause of Adult Blindness in the United States
![Page 7: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/7.jpg)
Disease Duration (yrs) 1 – 5 1 - 15Retinopathy NO very mild-to-moderateUrinary Albumin Excretion (mg/day) < 40 < 200
![Page 8: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/8.jpg)
DCCT, NEJM 1993
Hyperglycemia and Retinopathy in T1D
![Page 9: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/9.jpg)
Primary prevention group Secondary prevention group
-76%-54%
Seven field stereoscopic fundus photographyEarly Treatment Diabetic Retinopathy Study grading
DCCT, NEJM 1993
Hyperglycemia and Retinopathy in T1D
![Page 10: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/10.jpg)
Hyperglycemia and Retinopathy in T1D
DCCT & EDIC, NEJM 2000 & Arch Intern Med 2009
![Page 11: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/11.jpg)
DCCT & EDIC, NEJM 2000 & Arch Intern Med 2009
Hyperglycemia and Retinopathy in T1D
![Page 12: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/12.jpg)
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.
Rela
tive
Risk
HbA1C (%)
15
13
11
9
7
5
3
16 7 8 9 10 11 12
HbA1C and Relative Risk of Microvascular Complications
RetinopathyNephropathyNeuropathyMicroalbuminuria
20
DCCT, NEJM 1993
![Page 13: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/13.jpg)
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
![Page 14: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/14.jpg)
UKPDS, Lancet 1998
![Page 15: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/15.jpg)
UKPDS, Lancet 1998
Hyperglycemia and Retinopathy in T2D
![Page 16: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/16.jpg)
UKPDS, Lancet 1998
Hyperglycemia and Retinopathy in T2D
![Page 17: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/17.jpg)
![Page 18: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/18.jpg)
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.
UKPDS ACCORD
A1C reduction (%) 0.9 1.3
Retinopathy risk reduction (%)* 29 17 33
Retinopathy onset
(P=0.003)
Retinopathy progression(P=0.017)
Retinopathy progression(P=0.003)
![Page 19: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/19.jpg)
Hemmingsen B et al. Br Med J 2011
Hyperglycemia and Retinopathy
![Page 20: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/20.jpg)
Boussageon R et al. Br Med J 2011
Hyperglycemia and Retinopathy: the sooner the better
![Page 21: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/21.jpg)
RACCOMANDAZIONIRaccomandazioni generaliOttimizzare il compenso glicemico riduce il rischio e la progressione della retinopatia.(Livello della prova I, Forza della raccomandazione A)
![Page 22: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/22.jpg)
Predictors of Poor Glycemic Control
• Younger age• Longer diabetes duration • Weight <85th percentile• Not living in a 2-parent household• Type of diabetes care provider• Nonwhite race/ethnicity• Female gender• Lower parental education• Poor early glycemic control (2nd year after diagnosis;
predictive of poor glycemic control later)
Petitti DB, et al. J Pediatr. 2009;155:668-672.e1-3; Chemtob CM, et al. J Diabetes. 2011;3:153-157.
![Page 23: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/23.jpg)
Primary prevention group Secondary prevention group
-76%-54%
Seven field stereoscopic fundus photographyEarly Treatment Diabetic Retinopathy Study grading
DCCT, NEJM 1993
Hyperglycemia and Retinopathy in T1D
![Page 24: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/24.jpg)
![Page 25: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/25.jpg)
![Page 26: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/26.jpg)
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 variabilityGlucose
variabilityReluctance to intensify
therapyReluctance to intensify
therapy
High A1CHigh A1C
ComplicationsMorbidity Mortality
ComplicationsMorbidity Mortality
Quality of lifeQuality of life
Fear of hypoglycemia
Fear of hypoglycemia
Severe hypoglycemiaSevere hypoglycemia
ControversialControversial
![Page 27: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/27.jpg)
RACCOMANDAZIONIRaccomandazioni generaliOttimizzare il compenso glicemico riduce il rischio e la progressione della retinopatia.(Livello della prova I, Forza della raccomandazione A)
![Page 28: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/28.jpg)
Diabetic Retinopathy Management
Lesion Type Management 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
angiographyPreproliferative retinopathy • Optimal glucose and blood pressure control
• Panretinal scatter laser photocoagulationProliferative 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.
![Page 29: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/29.jpg)
Standards of Medical Care in Diabetes - 2015
![Page 30: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/30.jpg)
Standards of Medical Care in Diabetes - 2015
![Page 31: Impatto della terapia ipoglicemizzante sulla retinopatia diabetica Raffaele Napoli Dipartimento di Scienze Mediche Traslazionali Università Federico II](https://reader038.vdocument.in/reader038/viewer/2022102818/56649f555503460f94c78b54/html5/thumbnails/31.jpg)