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Screening for Eye and Kidney Complications and Dyslipidemia

Screening for Eye and Kidney Complications and Dyslipidemia. Brian Bucca, OD, FAAO David Maahs, MD R. Paul Wadwa, MD. Disclosures. Dr. David Maahs Merck: clinical trial support Dr. Paul Wadwa Merck: clinical trial support Dr. Brian Bucca. Objectives.

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Screening for Eye and Kidney Complications and Dyslipidemia

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  1. Screening for Eye and Kidney Complications and Dyslipidemia Brian Bucca, OD, FAAO David Maahs, MD R. Paul Wadwa, MD

  2. Disclosures • Dr. David Maahs • Merck: clinical trial support • Dr. Paul Wadwa • Merck: clinical trial support • Dr. Brian Bucca

  3. Objectives • The practitioner will be able to understand and apply current ADA guidelines for screening evaluation and management of nephropathy and dyslipidemia in youth with diabetes. • The practitioner will be able to identify risk factors, which will be useful in screening patients who are at risk for retinopathy progression.

  4. Outline • Nephropathy • Dyslipidemia • Retinopathy • Case Discussion

  5. Kidneys Nephropathy: persistent macroalbuminuria associated with changes in the kidney leading to abnormal ability to filter and HTN • Treatable with medications • Earliest sign is microalbuminuria • Failure to detect/treat can lead to macroalbuminuria, renal failure

  6. ADA Guidelines for T1D Youth • Annual screening >10y + T1D >5y • More frequent if values increasing • Methods • Spot, timed, 24 hour • Repeat if abnormal, 2/3 required for diagnosis of persistent abnormal microalbumin excretion (exercise, smoking, menstruation all effect results) Silverstein, Klingensmith et al, Diabetes Care, January 2005

  7. Albuminuria Definitions • Spot samples: • ACR (albumin-to-creatinine ratio) • Microalbuminuria: 30-299 mg/g • Macroalbuminuria: ≥300 mg/g • Timed overnight or 24 hour samples: • AER (albumin excretion rate) • Microalbuminuria: 20-199 μg/min • Macroalbuminuria: ≥200 μg/min

  8. Why Screen? • Opportunity to detect microalbuminuria during the reversible phase of diabetic nephropathy. • start ACE/ARB • intensify glycemic control

  9. Treatment • Angiotensin-converting enzyme inhibitors (ACE) • Glycemic control • Smoking cessation • Treat Hypertension if it exists • LDL treatment may be of benefit • Consider Nephrology referral

  10. Why is it Important? • Diabetic Nephropathy (DN) occurs in 20-40% of patients • Single leading cause of ESRD • Persistent MA is earliest stage of DN, also an established CVD risk factor • Patients with MA who progress to macroalbuminuria are likely to progress to ESRD • It is TREATABLE!!!

  11. Nephropathy Risk Factors • Poor blood sugar control • Smoking • Family history of high blood pressure or cardiovascular disease

  12. ISPAD guidelines 2007Differences • Screen: annually once 11y with 2y duration and 9y once 5y duration • Treatment: also include ARB • Definitions: 2.5-25 mg/mmol or 30-300 mg/g in a spot sample but with 3.5-25 mg/mmol in females because of lower creatinine excretion • Loss of nocturnal dippingearly marker of diabetic renal disease preceeding MA Donaghue etal, Pediatric Diabetes, 2007

  13. ADA 2008 Practice Guidelines • Type 2 Diabetes • Screen at diagnosis and annually • Adults: check serum creatinine annually to estimate GFR • With ACE/ARB/diuretic treatment monitor serum creatinine and K+

  14. Rates of MA in Youth with DM • SEARCH (Maahs, Diabetes Care ’07): • T1D: 9.2% • T2D: 22.2% • Australia (Eppens, Diabetes Care ’06): • T1D: 6% • T2D: 28%

  15. Complications in Type 2 Diabetes in Adolescents Pinhas-Hamiel, Zeitler. Lancet ‘07

  16. Cystatin C • Emerging as a marker of GFR associated with outcomes • Appears independent of age, sex, and muscle mass • Described as HbA1c for renal function (Perkins, Curr Diab Rep, ‘05) • Cystatin C is a stronger predictor of death and CV events in elderly persons than creatinine(Shlipak, NEJM, ‘06)

  17. Cystatin C • Why does Cystatin C reflect GFR? • stably produced by nucleated cells • freely filtered at the glomerulus due to a small molecular mass = increases as GFR decreases • not reabsorbed or secreted, metabolized in the proximal tubules.

  18. Cystatin C: Better Estimate of GFR than current equations Perkins, NEJM, 2005

  19. Perkins, JASN, 2005

  20. Dyslipidemia

  21. Breaking News! “Lipid screening and cardiovascular health in childhood” Clinical report from American Academy of Pediatrics • Just published in July 2008 Pediatrics • Overview of lipids screening in all children • Recommendations for screening and management in context of available evidence • Mention of youth with diabetes mellitus as a high risk group, cutpoint for LDL level • Discussion of metabolic syndrome SR Daniels, FR Greer, Committee on Nutrition, Pediatrics July 2008; 122(1): 198-208

  22. Dyslipidemia Background • Atherosclerosis starts in childhood • In adults, the risk for heart disease in patients with diabetes is equivalent to risk in patients with known coronary disease • Early detection of abnormal cholesterol level and/ or high blood pressure can decrease risk for heart disease later in life

  23. Dyslipidemia Background • Studies on lipid levels in childhood show an association with lipid levels in adults • Data on treating diabetic youth with lipid lowering medication are limited • No studies document lipid levels in childhood associated with CVD events in adulthood (studies do show association with cIMT)

  24. Dyslipidemia Background • In BDC data, lipid levels are elevated in 18 % of T1DM patients • But only 23 of 360 patients in latest data are on medication to treat dyslipidemia Maahs et al, J Pediatr 2005 Maahs, Wadwa et al, J Pediatr 2007

  25. Total Cholesterol, HDL, and non-HDL Cholesterol Abnormalities in T1DM subjects (n=682) compared to 2001-02 NHANES (n=3,798) 18.6% were abnormal for either TC or HDL Maahs et al, JPeds, 2005

  26. Sustained Lipid Abnormalities in T1DM Youth, n=360 subjects with 1,095 lipid measurements Maahs, Wadwa et al, J Pediatr 2007

  27. LDL by age and diabetes type in SEARCH Kershnar, JPediatr 2006

  28. Recommendations of the ADA on Lipid Screening and Management in Children and Adolescents with Diabetes ADA, Diabetes Care 2003, Kershnar, JPediatr 2006

  29. Dyslipidemia Evaluation Lipids screening for T1DM youth • If positive family history or unknown history • Lipids screening (fasting) after 2 yrs of age and glucose control obtained after diagnosis • If negative family history • Lipids screening after 12 yrs of age and glucose control obtained after diagnosis • Repeat every 5 years if normal (LDL< 100) ADA, Diabetes Care 2003 Silverstein, Klingensmith et al, Diabetes Care, January 2005

  30. Dyslipidemia Management • Lowering LDL has proven benefit in adults • Primary goal of therapy is to lower LDL to target: LDL (mg/dl) Normal Less than 100 Borderline 100-129 Abnormal 130 or higher

  31. Dyslipidemia Management If fasting lipids abnormal: • Optimize blood sugar control • Decrease fat in diet • Limit saturated fat to <7% of calories • Minimize intake of trans fat • Limit dietary cholesterol to <200 mg/day • Increase exercise; weight loss as necessary • Smoking cessation ADA, Diabetes Care 2003 Silverstein, Klingensmith et al, Diabetes Care, January 2005

  32. Dyslipidemia Management Pharmacologic therapy • Age > 10 years old • LDL > 160 mg/dl 130-159 mg/dl: consider based on profile or once lifestyle modification attempted • Statins (first line?) • Resins (approved for use in Pediatrics) • Fibric acid derivatives if TG > 1000 mg/dl* • ezetimibe (Zetia)

  33. Pharmacologic Class LDL-C Triglycerides HDL-C Bile acid-binding resins Decreases 10-30% Increases 3-10% Unchanged Fibric acid derivatives Decreases 5-10%* Decreases 30-60% Increases 5-10% Niacin Decreases 10-25% Decreases 5-30% Increases 15-25% HMG-CoA reductase inhibitors (statins) Decreases 20-40% Decreases 10-30% Increases 5-15% Lipid-Lowering AgentsMaximum Effect on Serum Lipid Levels * Fenofibrate may increase LDL-C levels.

  34. Dyslipidemia Management • Pharmacologic therapy • Goal is LDL < 100 mg/dl • ** Counsel youth ‘at risk’ for pregnancy regarding lipid lowering agents and stop drug immediately if pregnancy suspected Silverstein, Klingensmith et al, Diabetes Care, 2005; 28(1): 186-212

  35. Dyslipidemia Summary Current ADA guidelines recommend: • Screening of lipids beginning after 2 or 12 years of age depending on family history • Repeat at least every 5 years (every 2 yrs in T2DM) (more often if screening is abnormal) • Treatment options include: • Lifestyle modification (glycemic control, diet, exercise) • After 10 years old, consideration of oral medications depending on type and degree of lipid abnormality

  36. Research • Evidence in youth with diabetes is needed to support ADA guidelines • More research is needed in this area to start to prevent CVD early in youth with diabetes

  37. Cardiovascular Research at the BDC • CACTI (Coronary Artery Calcification in Type 1 Diabetes) • Study of coronary artery calcification progression in T1DM and non-DM young adults, now in year 9 of data collection • PI: Marian Rewers, MD, PhD • SEARCH for Diabetes in Youth • Multi-center epidemiologic study of diabetes in youth • Ancillary examined CVD risk in adolescents with T1DM and T2DM • Determinants of macrovascular disease in adolescents with T1DM • Assessment of CVD risk factors/ arterial stiffness measures in BDC cohort of T1DM and non-DM adolescents • PI: Paul Wadwa, MD • VAST (Vytorin And Simvastatin Trial) • Clinical trial of lipid lowering medications in youth with T1DM • PI: David Maahs, MD • *funding/ medications provided by Merck

  38. Research: Cardiovascular assessment study Determinants of macrovascular disease in adolescents with T1DM • Now enrolling! • Adolescents age 12- 19 years with T1DM for 5 yrs or longer • also recruiting control subjects (age 12-19 yrs) without diabetes or other significant medical issues • Fasting blood draw, urine collection • Arterial stiffness measures

  39. Research Determinants of macrovascular disease in adolescents with T1DM • For more information: Contact: Franziska Bishop, MS (303) 724-6764 Dr. Paul Wadwa (303) 724-6719 Dr. David Maahs (303) 724-6706

  40. Retinopathy

  41. Case Discussion

  42. Web Links • www.barbaradaviscenter.org • www.diabetes.org American Diabetes Association

  43. Thank You

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