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Complications of Diabetes

Complications of Diabetes. 영양병원 내과 이준엽. Classifications. Acute complications 1) Hypoglycemia 2) comas (DKA Vs HHS)

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Complications of Diabetes

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  1. Complications of Diabetes 영양병원 내과 이준엽

  2. Classifications • Acute complications1) Hypoglycemia2) comas (DKA Vs HHS) • Chronic complications1) Diabetic microvascular Cxs. (retinopathy, nephropathy, neuropathy)2) Diabetic macrovascular Cxs. (coronary, cerbral a. , foot ulcers, HTN)

  3. Acute Complications

  4. Chronic Complications

  5. Acute Complications - Hypoglycemia • IV or Oral glucoses • evaluations of cause (drug overdose? – PO Vs Insulin, other cause?) • managements?

  6. Acute Complications- Comas • ** Hydrations (ex. N/S 1 L full dropping) • ** Insulin?? (ex. N/S 500 + HR 100 IU) • Evaluations and Causes? (DKA Vs HHS) • Managements(Key points: deficiency of insulin)

  7. Chronic Complications • Diabetic microvascular Cxs. (retinopathy, nephropathy, neuropathy) • Diabetic macrovascular Cxs. (coronary, cerebral a. , foot ulcers, HTN)

  8. Prevention and treatment of microvascular complications • Glycemic control and microvascular complications • Blood pressure control and microvascular complications • Other preventive and therapeutic measures • Follow-up and specific treatment of nephropathy • Follow-up and specific treatment of retinopathy

  9. The Diabetes Control andComplications Trial (DCCT) • Multicenter, randomized study of type 1 diabetes patients • To assess effect of intensive glycemic control vs conventional therapy on: development and progression of retinopathy and other long-term complications • Results of this trial led to similar studies of type 2 diabetes patients DCCT Research Group. N Engl J Med. 1993;329:977-986.

  10. Overall Results of the DCCT Trial • Intensive control of blood glucose reduced risk of diabetic complications1) retinopathy onset ↓76% in patients with no retinopathy at baseline (P≤0.002)2) retinopathy progression ↓54% in patients with mild retinopathy at baseline (P≤0.002)3) nephropathy ↓54% (P<0.04)4) neuropathy ↓60% (P≤0.002) • There was, however, a 2- to 3-fold greater incidence of severe hypoglycemia DCCT Research Group. N Engl J Med. 1993;329:977-986.

  11. Relative Risk of Progression of Diabetic Complications

  12. Possible molecular mechanisms of diabetes-related complications. Harrison's Principles of Internal Medicine, 16th Edn

  13. Mechanisms of Glucose Related Complications ReuschJEB: J ClinInvest 2003;112:986-988

  14. Consequences of hyperglycemia-induced activation of protein kinase C (PKC) Vascular Health and Risk Management 2007:3(6):823-832

  15. Diabetic retinopathy • Annually ophthalmic exam

  16. Retinal Anatomy and Mechanisms of Diabetic Retinopathy. N Engl J Med 350:48, January 1, 2004 Review Article

  17. Diabetic retinopathy 실 명

  18. Optimal glycemic control (HbA1c < 7%) with gradual amelioration • Target blood pressure (< 130/80 mm Hg) • Monitor FO 3-6 monthly • FAG pre- and post- photocaogulation • Photocaogulation • Surgery 0 Advanced No Identify and correct reversible factors Prolif. Bckg Pre- Prolif. Control common CV risk factors Follow-up of retinopathy • Optimal glycemic control (HbA1c < 7%) • Target blood pressure (< 130/80 mm Hg) • Monitor FO 12 monthly • FAG only if FO suspect • Optimal glycemic control (HbA1c < 7%) with gradual amelioration • Target blood pressure (< 130/80 mm Hg) • Monitor FO 3-6 monthly • FAG pre- and post- photocaogulation • Photocaogulation • Optimal glycemic control (HbA1c < 7%) • Target blood pressure (< 130/80 mm Hg) • Monitor FO 12 monthly • Monitor FAG every 2 yrs • Photocaogulation only in case of macular edema • Optimal glycemic control (HbA1c < 7%) with gradual amelioration • Target blood pressure (< 130/80 mm Hg) • Monitor FO 6 monthly • FAG in preparation for photocaogulation • Photocaogulation

  19. grid focal panphotocoagulation + grid panphotocoagulation Photocoagulation Clinically significant Macular Edema Pre-proliferative and Proliferative Retinopathy

  20. Diabetic nephropathy • Annually 24hr urine protein

  21. Stages of Renal Involvement According to the Urinary Albumin Level in Patients with Type 2 Diabetes Mellitus. N Engl J Med 346:1145, April 11, 2002 Clinical Practice

  22. Recommended Interventions to Slow the Progression of Renal Disease in Patients with Type 2 Diabetes. N Engl J Med 346:1145, April 11, 2002 Clinical Practice

  23. Suggested Medications for Hypertension in Patients with Type 2 Diabetes. N Engl J Med 346:1145, April 11, 2002 Clinical Practice

  24. 0 Macro & ESRD Normo Macro &  GFR Identify and correct reversible factors 30 mg Micro Macro & = GFR 300 mg Control common CV risk factors • Refer to renal team • RRT education and modality selection • Access creation (no temporary) • Start RRT early in diabetics • Avoid malnutrition • Optimise Hb and Ca/P control Follow-up of nephropathy • Optimal glycemic control (HbA1c < 7%) • Target blood pressure (< 130/80 mm Hg) • Monitor UAE 12 monthly • Monitor GFR 12 monthly • Refer to renal team • Optimal glycemic control, but avoid hypoglycemia • Target blood pressure • Maintain RAS blockade, except in patients with GFR>15 ml/min • Restrict dietary protein (to 0.8 or even 0.6 g/kg bw/d), but avoid malnutrition • Restrict P (add binders), K & Na • Control Hb with EPO & Fe • Monitor UAE 3 monthly • Monitor GFR 3 monthly • Optimal glycemic control • Target blood pressure • Control UAE irrespective of BP with RAS blockade • Monitor UAE 6 monthly • Monitor GFR 12 monthly • Optimal glycemic control • Target blood pressure (< 125/75 mm Hg) • Control UAE irrespective of BP with RAS blockade • Restrictdietaryprotein(to0.8 g/ kg bw/d) in selected cases • Monitor UAE 3 monthly • Monitor GFR 6-12 monthly

  25. Renal replacement therapy Options GFR GFR 50 30 15 10 5 50 30 15 10 5 Transplant ? No Yers Kidney + pancreas Kidney HD PD living cadaveric Waiting list Waiting list Access Start HD Start PD Trapianto

  26. Diabetic neurophathy • Every visit, foot exam

  27. Sensory Foot Exam Findings

  28. Diabetic foot ulcers

  29. Diabetic foot ulcers

  30. Consensus guidelines: treatment planning options. Mayo Clin Proc. 2006;81[4 suppl]:S12-S25.

  31. Monitoring Parameters for Control of Complications Every visit Blood Pressure Foot Exam (55% achieve goal) _______________________________________________________ 3-6 months A1C - Every 3 months if treatment changes or not meeting goals - Every 6 months if stable _______________________________________________________ Annual Dilated Eye Examination (63% achieve goal) Lipid Levels* Microalbumin _______________________________________________________ *Every 2 years if levels fall in lower risk categories

  32. Macrovascular complications • Coronary A. diseases • Cerebral A. diseases • Foot ulcers • Hypertensions

  33. Causes of Death in People with Diabetes 50 40 30 % deaths 20 10 0 Ischaemic Heart Disease Other Heart Disease Diabetes Cancer Stroke Infection Other Geiss LS, et al. In: Diabetes in America, 2nd ed. 1995. Bethesda, MD: NIH; 1995

  34. TYPE 2 DIABETES Hyperglycaemia (Insulin resistance) Hypertension Dyslipidaemia Central obesity Impaired fibrinolysis Endothelial dysfunction Hypertriglycaeridemia Proinflammatory state Low HDL-C Small, dense LDL-C CVD

  35. Relationship Between Glycemic Control and Coronary Heart Disease Events in Type 2 Diabetes Patients (Ages 65 to 74) 25 20 HbA1c<7.0% 15 HbA1c³7.0% 3.5-yr Incidence (%) 10 5 0 <6 ³6 Duration of Diabetes (yr) Kuusisto J et al. Diabetes. 1994;43:960-967.

  36. UKPDS Impact of Tight*vs Less Tight† Blood Pressure Control on Diabetes-Related Endpoints Relative risk for tight control (95% CI) P Value Relative risk reduction (95% CI) Any DM-related endpoint 0.76 (0.62–0.92) 0.005 DM-related deaths 0.68 (0.49–0.94) 0.02 All-cause mortality 0.82 (0.63–1.08) 0.17 Myocardial infarction 0.79 (0.59–1.07) 0.13 Stroke 0.56 (0.35–0.89) 0.01 Peripheral vascular disease 0.51 (0.19–1.37) 0.17 Microvascular complications 0.63 (0.44–0.89) 0.009 *n=758 (mean achieved blood pressure of 144/82 mmHg) †n=390 (mean achieved blood pressure of 154/87 mmHg) 1 0.1 10 Favors tightcontrol Favors less tight control Adapted from UKPDS Group. BMJ. 1998;317:703–713.

  37. Relative Risk Reduction With ACEIsin ABCD, CAPPP and FACET Acute Myocardial Infarction Cardiovascular Event All-cause Mortality Stroke NS % relative risk reduction P=0.01 P<0.001 P<0.001 Pahor M, et al. Diabetes Care. 2000;23:888-892.

  38. DIABETIC HYPERTENSION Combinations of two or more drugs are usually needed to achieve the target goal of <130/80 mmHg. Thiazide diuretics, BBs, ACEIs, ARBs, and CCBs are beneficial in reducing CVD and stroke incidence in patients with diabetes. ACEI- or ARB-based treatments favorably affect the progression of diabetic nephropathy and reduce albuminuria, and ARBs have been shown to reduce progression to macroalbuminuria. The seventh Report of the Joint National Committee on Prevention, Detection, Evaluation of High Blood Pressure, May 2003

  39. Intensive blood pressure control in diabetic patients hypotensive effect criteria of choice Function kidney:  RPF ( Re>Ra) = GFR   P  proteinuria retina:  capillary P;  endothelial dysfunction vessels:  constr. (resp. ET-1)  dilat (NO) heart:  myocardial function & coronary flow Structure  kidney, retina vessels & heart remodeling x  cell growth & matrix production Carbohydrate metabolism  or = insulin secretion & sensitivity = response to hypoglycemia Lipid metabolism  or = LDL-C & TG  or = HDL-C protection of target organs influence on glycolipid metabolism side effects

  40. Nephropathy Retinopathy Coronaric evelts Stroke Thiazidic diuretics Favorable (A) Unknown Unknown Favorable (A) Loop diuretics Unknown Unknown Unknown Unknown Central adrenergic agents Unknown Unknown Unknown Unknown -blockers Favorable (A) Favorable (A) Favorable (A) Favorable (A) -blockers Controversial Unknown Controversial Unknown Ca-channel blockers (DHP) Controversial Unknown Controversial Favorable (A) Ca-channel blockers (non-DHP) Unknown Unknown Favorable (C) Unknown ACE-inhibitors Favorable (A) Favorable (A) Favorable (A) Favorable (A) AT1 receptor antagonists Favorable (A) Unknown Favorable (A) Favorable (A) Intensive blood pressure control in diabetic patients Type A evidence referred to UKPDS (low number of events)  CV events (mainly heart failure) ALLHAT  CV events (mainly coronaric) ABCD (nisoldipine) metanalysis(nifedipine) Reduce GFR and doesn’t ameliorate proteinuria (afferent arteriole vasodilation) Short-term studies with few patients Effective on proteinuria (GFR ?) 2003 ADA Clinical Practice Recommendations

  41. Step 1Low sodium diet(100 mEq/day),body weight control, physical exercise, stop smoking Step 2ACE-inhibitorsorAng-II antagonists Step 3Ca-antagonist (non-DHP) Step 4Diuretics, -blockers or -blockers Step 5 Central adrenergic or vasodilators Intensive blood pressure control in diabetic patients

  42. one drug at low-dose two drugs at low-dose other drug at low-dose same drug at full-dose same combination at full-dose other drug at low-dose monotheraphy at full-dose combination combination of three drugsi at full-dose Intensive blood pressure control in diabetic patients Arterial hypertension untreated BP level other risk factors target organ damage BP target not reached BP target not reached

  43. Intensive blood pressure control in diabetic patients diureticis -blockers AT1RB -blockers CCBs ACEi

  44. Antiplatelet therapy • Primary prevention • DM1 and DM2 patients >30 years • with high CV risk • CAD family history • Smoking • Hypertension • Obesity (>120% BMI); BMI >27.8 kg/m2 M or >27.3 kg/m2 F • Dislipidemia: TC >190 mg/dl; LDL-C >100 mg/dl; HDL-C <45 mg/dl M or <55 mg/dl F; TG >150 mg/dl • Albuminuria (micro or macro) aspirin(tablets) 81–325mg/day • Contraindications • Allergy • Bleeding tendency • Anticoagulating treatment • Recent gastro-intestinal bleeding • Clinically active liver disease • Age <21 years ( Reye’s syndrome) • Secondary prevention • DM1 and DM2 patients with clinical • history of cardiovascular disease • myocardial infarction or angina • Stroke or TIA • Peripheral vascular disease • By-pass surgery clopidogrel ticlopidine

  45. Reduce macrovascular complications • Good glycaemic control • LDL-Cholesterol <100 mg/dL (Statins) • BP <130/80 mm Hg (ACE inhibitors) • Weight loss ~5% to 10% body weight • Aspirin • No Smoking • Realistic exercise

  46. Key message of Diabetic complications • Intensive glucose control • Restrictive BP control by using ACEIs(<130/80) • Stop smoking • Control dyslipidemia • Exams (foot, OPH, Lab …) • Aspirins

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