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  • GLP has a half-life of < 2 min so it can’t be used as therapy. Necessary to use analogs exenatide clinical effects last up to 8 hours
  • At low titers, the antibodies do not affect the effectiveness of exenatide. Delays gastric emptying. Counsel patients to take their other meds 1 h before byetta
  • Most patients fail lifestyle interventions so the consensus panel decided they should be put on metformin at the same time
  • Important in both inpatient and outpatient setting
  • Secretagogues not considered synergistic when given with insulin
  • There aren’t many head-to-head comparisons of the ability of the different agents to achieve glucose control
  • Approximately 5,000 Patient included for 1,000 years of follow-up in this study Incidence rates and 95% confidence intervals for myocardial infarction and microvascular complications by category of updated mean haemoglobin A1c concentration, adjusted for age, sex, and ethnic group, expressed for white men aged 50­54 years at diagnosis and with mean duration of diabetes of 10 years
  • Atherosclerosis = plaque formation Essential hypertension = no identifiable cause for hypertension Part of syndrome X (metabolic syndrome) especially when hypertriglyceridemia and decreased HDL are included
  • If diabetic patient is initially between 130-140/80-90 you may begin lifestyle adjustment for 3 months if you feel your patient will return to clinic. If goal not achieved, then you must initiate pharmacotherapy management
  • ACE-I, ARB and Thiazide diuretic medications preferred combo = Monitor Renal function and Potassium (Hyper-K ACEI/ARB and Hypo-K HCTZ) ACE-I vasodilate at the efferent arteriole Non-DCCB = Verapamil/Diltiazem SBP > 160 or DBP > 100 requires immediate drug therapy
  • Treatment with aspirin: 30% decrease in myocardial infarction 20% decrease in stroke Not studied in person < 30 and person < 21 = increased chance of Reyes Symdrome
  • ACE-I vasodilate at the efferent arteriole Non-DCCB = Verapamil/Diltiazem
  • Pulses: dorsalis pedis and posterior tibialis

Transcript

  • 1. Management of the Patient with Type 2 Diabetes Gretchen M. Ray, Pharm.D. Cardiovascular Pharmacotherapy Resident University of New Mexico College of Pharmacy
  • 2. Objectives
    • Provide diabetes screening criteria for adults
    • Describe available pharmacologic treatment options for type 2 diabetes including advantages/disadvantages of therapy and contraindications
    • Given a patient case recommend appropriate lifestyle modifications and pharmacotherapy to achieve glycemic goals
  • 3. Objectives
    • Distinguish between microvascular and macrovascular complications
    • Provide screening criteria for nephropathy, neuropathy, and retinopathy
    • Provide treatment strategies for the prevention and treatment of micro and macrovascular complications
  • 4. Epidemiology of Type 2 DM
    • In 2005 20.8 million people (7% of the US population) had diabetes
      • 14.6 million diagnosed
      • 6.2 million undiagnosed
    • Type 2 diabetes accounts for 90-95% of patients with diabetes
    • In 2002 total indirect and direct medical costs for diabetes = $132 billion
    CDC. National diabetes fact sheet. 2005 available at www.cdc.gov/diabetes/pubs/pdf/ndfs_2005.pdf
  • 5. Risk factors for type 2 diabetes
    • Physically inactive
    • 1 st degree relative with diabetes
    • Minority ethnic groups
    • Gestational diabetes or delivering a baby >9 lbs
    • Hypertension
    • HDL <35 mg/dL and/or triglycerides >250 mg/dL
    • Polycystic ovary syndrome
    • Previous impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)
    • History of vascular disease
    • Psychiatric illness
  • 6. Diagnosis of diabetes
    • Symptoms of diabetes + casual plasma glucose ≥ 200 mg/dl
    • FPG ≥ 126 mg/dl
    • Oral glucose tolerance test (OGTT): 2-h postload glucose ≥ 200 mg/dl
    OR OR
  • 7. Definition of “pre-diabetes”
    • Impaired fasting glucose (IFG) = FPG 100-125 mg/dl
    • Impaired glucose tolerance (IGT) = 2-h post load glucose 140-199 mg/dl
    • IFG and IGT indicate a risk factor for diabetes and cardiovascular disease
  • 8. Diabetes Screening
    • Screening identifies asymptomatic patients who might have diabetes
    • Consider in patients ≥ 45 years especially if their BMI ≥ 25 kg/m 2
    • Screen patients < 45 years old if they are overweight + an additional risk factor
    • FPG should be done initially
    • Repeat screening every 3 years
  • 9. Oral Therapies
  • 10. Metformin
    •  hepatic glucose production,  intestinal glucose absorption,  insulin sensitivity
    • Efficacy:  A1C 1.5%
    • Adverse effects
      • Primarily GI (up to 50%)
        • Diarrhea, abdominal bloating, nausea
        • Titrate dose at weekly intervals to minimize AEs
        • Give with meals
      • Lactic acidosis- rare
        • Monitor SCr
  • 11. Contraindications to Metformin
    • Renal impairment SCr >1.5 for men, >1.4 for women
    • Radiocontrast studies
    • Age >80 unless normal GFR
    • Hypoxia
    • Liver dysfunction
    • Alcoholism
    • Heart Failure requiring pharmacologic therapy
      • According to package insert
    • Should heart failure be a contraindication to metformin?
  • 12. Improved Clinical Outcomes Associated with Metformin in Patients with Diabetes and Heart Failure
    • Investigate the association between metformin and clinical outcomes in patients with HF and diabetes
    • Retrospective study
    • Primary outcome: all-cause mortality at 1 year and end of follow-up
    • Secondary outcome: all-cause hospitalizations at 1 year and end of follow-up
    Eurich DT, et al. Diabetes Care. 2005;28:2345-51
  • 13. Improved Clinical Outcomes Associated with Metformin in Patients with Diabetes and Heart Failure Eurich DT, et al. Diabetes Care. 2005;28:2345-51 0.86 (0.77-0.96) 0.83 (0.70-0.99) 1.0 Combined endpoint 0.93 (0.83-1.05) 0.87 (0.73-1.05) 1.0 Adjusted all-cause hospitalization, HR (95% CI) 0.61(0.52-0.72) 0.70 (0.54-0.91) 1.0 Adjusted all-cause mortality, HR (95% CI) Combination therapy (n=852) Metformin monotherapy (n=208) Sulfonylurea monotherapy (n=773)
  • 14. Improved Clinical Outcomes Associated with Metformin in Patients with Diabetes and Heart Failure
    • Lower all-cause mortality with metformin
    • No increase in hospitalizations associated with metformin
    • Observational study
      • Cannot prove that metformin is efficacious in this population
    Eurich DT, et al. Diabetes Care. 2005;28:2345-51
  • 15. Sulfonylureas
    • ↑ insulin secretion from pancreatic β -cells
    • Efficacy: ↓ A1C 1.5%
    • Glyburide
      • Not recommended if CrCl < 50 ml/min (use a different sulfonylurea)
    • Glipizide
      • Not recommended if CrCl < 10 ml/min
    • Glimepiride
      • Not recommended if CrCl < 22 ml/min
    • Response of sulfonylureas plateaus after half the max dose
    • Reduced GI absorption if blood glucose > 250 mg/dL
  • 16. Sulfonylureas Adverse Effects
    • Hypoglycemia
      • Elderly patients
      • Hepatic/renal impairment
      • Combination therapy
    • Weight gain
  • 17. Thiazolidenediones (TZDs) Insulin Sensitizers
    • TZDs are PPAR- gamma receptor activators
    • ↑ insulin sensitivity
      • Primarily in the peripheral tissue
    • Efficacy:  A1C 0.5-1.4%
    • Effect may not be seen for 4 weeks
    • Rosiglitazone (Avandia ® )
      • Initial dose 4 mg/day, Max dose 8 mg/day
    • Pioglitazone (Actos ® )
      • Initial dose 15-30 mg/day, Max dose 45 mg/day
  • 18. Adverse Effects/Contraindications of TZDs
    • AE’s
    • Fluid retention and peripheral edema
    • Weight gain
      • Fluid retention is a major contributor
      • Redistribution of adipose tissue
    • New-onset heart failure
      • < 1%
      • 2-3% when combined with insulin
    • CI’s
    • ALT > 2.5 x upper limit of normal
    • Hepatic disease
    • Alcohol Abuse
    • HF NYHA class III or IV (see following slides)
    Granberry MC, et al. Am J Health-Syst Pharm. 2007;64:931-6
  • 19. TZD Use In Heart Failure
    • Use of TZDs in patients with NYHA class I or II HF
      • May be used with initiation of treatment at the lowest dosage (rosiglitazone 2 mg daily or pioglitazone 15 mg daily)
      • Observe for weight gain, edema, or exacerbation of HF
    • Do not use TZDs in patients with NYHA class III or IV HF
    Nesto RW, et al. Diabetes Care. 2004;27:256-63
  • 20.  
  • 21. Meta-analysis of MI Risk With Rosiglitazone
    • 42 trials comparing rosiglitazone with placebo
      • 15,560 patients received rosiglitazone
      • 12,283 patients assigned to comparator groups
      • 24-52 week duration of trials
      • Mean baseline A1C 8.2% for both groups
    Nissen SE, et al. N Engl J Med. 2007;356:1-15
  • 22. Meta-analysis of MI Risk With Rosiglitazone Nissen SE, et al. N Engl J Med. 2007;356:1-15 0.06 1.64 (0.98-1.74) 22 39 Death from CV causes # events 0.03 1.43 (1.03-1.98) 72 86 Myocardial Infarction # events P value Odds Ratio (95% CI) Control n= 11,634 Rosiglitazone n= 14,371
  • 23. PROactive Trial
    • Primary objective: Determine if pioglitazone reduces CV morbidity and mortality in patients with diabetes
    • Pioglitazone vs. placebo
      • ↓ Triglycerides 11% vs. 1.8% ↑
      • ↑ LDL 7.2% vs. 4.9%
      • ↓ LDL/HDL 9.5% vs. 4.2%
    • Non-significant reduction in the primary endpoint
    Dormandy JA, et al. Lancet. 2005;366:1279-89
  • 24. PROactive Sub-analysis
    • Evaluated same endpoints in patients with prior MI
    • Significant ↓ in fatal/nonfatal MI excluding silent MI with pioglitazone
      • 5.3% pioglitazone vs. 7.2% placebo p=0.0453
    • Results for rosiglitazone and pioglitazone recently confirmed with two new meta-analyses
    Erdmann E, et al. J Am Coll Cardiol. 2007;49:1772-80
  • 25. HF in PROactive Dormandy JA, et al. Lancet. 2005;366:1279-89 0.634 22 (1%) 22 25 (1%) 25 Fatal HF 0.007 108 (4%) 153 149 (6%) 209 HF with hospital admission 0.003 90 (3%) 117 132 (5%) 160 HF w/o hospital admission <0.0001 198 (8%) 302 281 (11%) 417 Any report of HF # Patients (%) # Events # Patients (%) # Events P value Placebo n = 2633 Pioglitazone n = 2605
  • 26. FDA Updates- August 14, 2007
    • Rosiglitazone and pioglitazone received a “boxed warning” regarding CHF
    www.fda.gov Actos prescribing information. August 2007
  • 27. FDA Updates: November 19, 2007
    • MI risk added to rosiglitazone boxed warning
    Avandia prescribing information. November 2007
  • 28. Sitagliptin (Januvia ® )
    • DPP-4 inhibitor
      • Prevents the degradation of endogenous GLP-1
      • Results in a rise in postprandial endogenous GLP-1 levels
    Lauster CD et al. Am J Health Syst Pharm. 2007;64:1265-73 Sitagliptin
  • 29. Sitagliptin (Januvia ® )
    • Efficacy:  A1C 0.5-0.7%
    • 100 mg PO once daily
      • CrCl 30-50 ml/min 50 mg/day
      • CrCl <30 ml/min 25 mg/day
    • Approved for monotherapy or combination therapy
    • Weight neutral
    • Side effects similar to placebo
    • No contraindications identified yet
  • 30. Non-Oral Therapies
  • 31.  
  • 32. Glucagon-like peptide 1 (GLP-1) agonists
    • Exenatide (Byetta ® )
    • Glucagon-like-peptide-1 (GLP-1) analog
      • Incretin mimetic
      • Resistant to degradation by dipeptidyl peptidase-4 (DPP-4)
      • Suppresses high glucagon levels
      • Delays gastric emptying (can affect absorption of other medications)
    • Efficacy: ↓ A1C 0.5-1%
    • Dosing:
      • 5 mcg SC twice daily within 60 min of meals
      • Increase to 10 mcg bid after 4 weeks
    • FDA approved for type 2 diabetes in patients on metformin, sulfonylurea, TZD, or a combination who are not at goal
      • Not yet approved for use with basal insulin
  • 33. GLP-1 Physiology
  • 34. Exenatide adverse effects/contraindications
    • AE’s
      • N/V, diarrhea (30-45%)
      • Modest weight loss (a good side effect)
      • Hypoglycemia especially in combination with sulfonylureas
      • Anti-exenatide antibodies
    • Monitoring
      • Renal function
      • A1C in 3 months
    • CI’s
      • Type 1 diabetes
    • Precautions
      • CrCl < 30 ml/min
      • Gastroparesis
      • Hypoglycemia
  • 35. Pramlintide (Symlin ® )
    • Synthetic analog of human amylin
      • Suppresses glucagon secretion
        • Suppression of endogenous glucose from liver
      • Slows gastric emptying
        • Less rapid glucose appearance in the circulation
      • Regulates food intake due to central modulation of appetite
        • Weight loss
  • 36. Pramlintide (Symlin ® )
    • FDA approved for Type 1 or 2 diabetes in patients on optimal insulin therapy who are still not at goal
      • With or without metformin and/or sulfonylurea therapy
    • Efficacy:  A1C ~0.1-0.4% in type1 and 0.3-0.7% in type 2
    • 60 mcg (10 units) SC titrate to 120 mcg (20 units) before major meals (Type 2 dosing)
      • Dosed in mcg but drawn up in an insulin syringe
      • www.symlin.com/7522-Type-2-Dosing.aspx
    • Administered in conjunction with mealtime insulin
  • 37. Pramlintide (Symlin ® )
    • Adverse Effects
    • Insulin-Induced Severe Hypoglycemia:
    • Hypoglycemia will occur within 3 hours of injection
    • Must reduce pre-meal insulin by 50% at initiation to prevent serious reactions
    • Further reduction in insulin may be needed as dosage of pramlintide is adjusted
    • Contraindications
    • Diagnosis of gastroparesis
    • Hypoglycemia unawareness
    • A1C > 9.0%
    • Recurrent severe hypoglycemia requiring assistance during past 6 months
    • Using other medications that stimulate gastrointestinal motility
    • Pediatrics
  • 38. Glycemic Goals
  • 39. Glycemic Control
    • ADA Guidelines
    • A1C < 7.0%
      • <6.5 may further reduce complications
    • Fasting glucose 90-130 mg/dl
    • Peak postprandial glucose <180 mg/dl
      • 1-2 hours after the start of the meal
    • AACE Guidelines
    • A1C < 6.5%
    • Fasting glucose < 110 mg/dl
    • 2-h postprandial glucose <140 mg/dl
  • 40. A1C and Meal Plasma Glucose Levels
    • A1C should be as close to normal for the individual patient
    • Use less intensive goals for patients with risk for hypoglycemia
    • Target postprandial glucose if A1C goals not met after reaching preprandial goals
      • Target fasting glucose first!
    345 12 310 11 275 10 240 9 205 8 170 7 135 6 Mean Plasma glucose mg/dl A1C
  • 41. Self-Monitoring of Blood Glucose (SMBG)
    • At least 3 times/day if on insulin injections
    • If on orals, just use SMBG to help them achieve their glycemic goals
    • Use the data to make decisions on what therapy to add
  • 42.
      • Diabetes Care 2007;30(Suppl 1)
  • 43. Lifestyle + Metformin- Step 1
    • Titrate metformin to max dose over 1-2 months
    • TZDs and sitagliptin are also approved for monotherapy
    • Consider adding other oral medications if there is persistent hyperglycemia
  • 44. Lifestyle Modifications
  • 45. Diet
    • Weight loss will reduce insulin resistance
    • Saturated fat < 7 % of total daily calories
    • Carbohydrates should be from fruits, vegetables, whole grains, legumes, low fat milk
      • Low carb diets < 130 g/day not recommended for weight loss
    • Recommend sugar alcohols and nonnutritive sweeteners
    • Limit alcohol to 1 drink/day for women 2 drinks/day for men
      • If on insulin or a secretagogue drink alcohol with food to avoid hypoglycemia
  • 46. Exercise
    • 150 min/week of moderate-intensity aerobic activity (50-70% of max heart rate)
    • 90 min/week of vigorous aerobic exercise (>70% of max heart rate)
    • Resistance exercise 3 times a week
    • Improves glycemia
    OR
  • 47. Diabetes Self-Management Education (DSME)
    • All patients with diabetes should receive DSME after diagnosis
    • Teaches patients about the disease and how to improve self care
    • Should be conducted by either a CDE or health care professional with recent experience in diabetes management
  • 48.  
  • 49. Additional Medications - Step 2
    • Add within 2-3 months of initiation of therapy
    • Sulfonylurea
      • Cheapest option
    • TZDs
      • More expensive
      • Cardiac risk with rosiglitazone
    • Insulin
      • Most effective option
      • Consider in patients with A1C >8.5% or symptoms of hyperglycemia
      • Initiate with basal insulin
  • 50. Step-2 Alternatives
    • Sitagliptin
    • Glinides
    • Exenatide
  • 51.  
  • 52. Step-3 Initiate or intensify insulin therapy
    • Start or intensify insulin if lifestyle + metformin + a 2 nd medication have not attained goal A1C
    • Third oral medication can be considered if A1C is close to goal <8.0%
      • Expensive, not as effective as insulin
      • Exenatide could be used at this step
    • D/C insulin secretagogues (sulfonylurea or glinides) when pre-prandial rapid insulin is started
  • 53. Long Acting Insulin 10 units or 0.2 units/kg Increase dose 2 units q 3 days until fasting levels 70-130 mg/dl A1C ≥ 7% after 2-3 months? No Continue regimen Check A1C q 3 months Check pre-meal BG & add 2 nd injection ~4 units before meal Yes Pre-Lunch BG high: Add rapid acting at breakfast Pre-Dinner high: Add rapid acting at lunch Pre-Bed high: Add rapid acting at dinner A1C ≥ 7% after 2-3 months? Nathan DM, et al. Diabetes Care 2006;29
  • 54. A1C ≥ 7% after 2-3 months? Yes Recheck pre-meal BG and add another injection. Check 2-h postprandial BG and adjust pre-prandial insulin dose No Continue regimen and check A1C q 3 months Nathan DM, et al. Diabetes Care 2006;29
  • 55. Pramlintide Exenatide Sitagliptin TZD Exenatide
  • 56. CASE 1
    • JK is a 59 year old male presenting for a follow-up visit to the diabetes clinic.
    • Past Medical History
      • Type 2 diabetes
      • Hypertension
      • Coronary artery disease
      • Chronic renal insufficiency
  • 57. CASE 1
    • Medications
    • Metformin 1000 mg BID
    • Glyburide 10 mg BID
    • Pioglitazone 45 mg once daily
    • Metoprolol XL 50 mg once daily
    • Fosinopril 20 mg once daily
    • Aspirin 81 mg once daily
    • Labs (fasting)
    • Glucose 170 mg/dL
    • A1C 9.0%
    • SCr 1.7 mg/dL
    • CrCl 70 ml/min
  • 58. CASE 1
    • Which diabetes medication on his profile is contraindicated and should be discontinued?
    • A . Metformin
    • B . Glyburide
    • C . Pioglitazone
  • 59. CASE 1
    • Why?
    • A . Coronary artery disease
    • B . Renal insufficiency
    • C . Drug Interaction
    • D . Non-adherence
  • 60. CASE 1
    • Which one of the following would be most appropriate to replace the discontinued medication?
    • A . Glipizide XL 20 mg PO once daily
    • B . Insulin aspart 4 units SC before breakfast
    • C . Insulin glargine 10 units SC at bedtime
    • D . Pramlintide 60 mcg SC before meals
  • 61. Complications of Diabetes
  • 62. Complications of Uncontrolled Diabetes Hanefeld M, et al. Diabet Med. 1997;14(suppl 3):S6 HbA 1C PPG Hyperglycemia Spike Continuous Chronic Toxicity Acute Toxicity Tissue Lesions Diabetic Complications Microvascular Macrovascular Nephropathy Neuropathy Retinopathy PVD MI Stroke
  • 63. Relative Risk of Progression of Diabetic Complications by Mean HbA 1c * Updated Mean HbA 1c (%) Stratton IM, et al. BMJ. 2000;321:405-12. Adjusted Incidence per 1000 person years 6 7 8 9 10 11 *Based on UKPDS 35 data
  • 64. Macrovascular Complications
  • 65. Macrovascular Complication Statistics
    • CVD and Stroke
      • Adults with DM have heart disease death rates 2-4x higher than non-diabetics
      • Risk for stroke is 2 to 4x higher and risk of death from stroke is 2.8x higher than in non-diabetics
    U.S. Department of Health and Human Services, National Institute of Health, 2005.
  • 66. Macrovascular Complications
    • ~ 80% of all diabetic mortality
      • 75% from coronary atherosclerosis
      • 25% from cerebral or peripheral vascular disease
    • > 75% of all hospitalizations for diabetic complications
    • > 50% of patients with newly diagnosed type 2 diabetes have CHD
    National Diabetes Data Group. Diabetes in America. 2 nd . Ed. NIH; 1995.
  • 67. Insulin Resistance and Atherosclerosis Accelerated atherosclerosis Clinical diabetes Hyperinsulinemia Impaired glucose tolerance Hypertriglyceridemia Decreased HDL-C Essential hypertension Insulin resistance
  • 68. Heart Disease and Diabetes
    • Intensive treatment of hyperglycemia
    • Therapy for insulin resistance
    • Appropriate lipid management
    • Aggressive blood pressure control
    Treatment of CVD in diabetes is similar to therapy for non-diabetic individuals, the risk of CVD is much higher and the benefits of therapy are greater
  • 69. Hypertension
    • Defined as BP ≥ 140/90 mmHg
      • GOAL BP: < 130/80 mmHg
    • 20 – 60% of Diabetics have HTN
    • Epidemiologic evidence from the UKPDS indicate that each 10 mmHg decrease in mean SBP results in:
      •  12% any DM complication
      •  15% any DM-related death
      •  11% MI
      •  13% microvascular complications
    American Diabetes Association. Diabetes Care. 2007;30:S4-S41.
  • 70. Hypertension
    • Weight loss
      •  1 kg results in  of MAP ~ 1 mmHg
    • Sodium restriction
      • In non-diabetic patients reduces SBP ~ 5 mmHg and DBP ~2 - 3 mmHg
    • Drug Therapy (If SBP ≥ 140 mmHg or DBP ≥ 90 mmHg or lifestyle modification failure)
      • 1 st choice: ACE-I or ARB
      • 2 nd choice: Thiazide, β -Blocker, or Non-DCCB
    JNC 7 report. JAMA 2003;289:2560-72.
  • 71. Cholesterol Management
    • Screening:
      • Fasting lipid panel at least annually
      • More often if needed to achieve goals
      • In adults with low-risk lipid values, may obtain fasting lipid panel every 2 years
    • Goals:
      • LDL < 100 mg/dL
        • Optional: LDL <70 mg/dL
      • TG < 150 mg/dL
      • HDL:
        • > 40 mg/dL for males
        • > 50 mg/dL for females
    American Diabetes Association. Diabetes Care .2007;30:S4-S41.
  • 72. Macrovascular Complications
    • Aspirin Therapy: 75 – 162 mg/day
    • Primary prevention in those with ↑ CVD risk :
      • Family Hx of CVD
      • Tobacco use
      • HTN
      • Albuminuria
      • Lipids: TC >200; LDL >100; HDL < 45 (or 55) & TG >200
      • Age ≥ 40 years
    • Secondary prevention in those with DM + CVD
    • Not recommended for patients < 30 years-old
    American Diabetes Association. Diabetes Care .2007;30:S4-S41.
  • 73. Macrovascular Complications
    • Smoking cessation
      • Advise all patients not to smoke
      • Provide smoking cessation counseling and other forms of treatment if needed
    American Diabetes Association. Diabetes Care .2007;30:S4-S41.
  • 74. Management Summary for Macrovascular Complications American Diabetes Association. Diabetes Care .2007;30:S4-S41. Macrovascular Complications Goals Hypertension Dyslipidemia
    • LDL < 100 mg/dL
      • Optimal < 70 mg/dL
    • TG < 150 mg/dL
    • HDL:
      • > 40 mg/dL – Male
      • > 50 mg/dL - Female
    • Blood Pressure:
    • < 130/80 mmHg
    Treatment
    • Weight loss
    • Sodium restriction
    • ACE-I / ARB
    • Everyone needs:
    • Aspirin
    • Lifestyle modifications
    • Smoking Cessation
    • Statin
  • 75. Microvascular Complications
  • 76. Relative Risk of Progression of Diabetic Complications by Mean HbA 1c * Skyler JS ,et al. Endocrinol Metab Clin North Am . 1996;25:243-54. Relative risk 6 7 8 9 10 11 12 15 13 11 9 7 5 3 1 HbA 1c (%) Diabetic retinopathy Nephropathy Neuropathy Microalbuminuria *Based on DCCT data
  • 77. Diabetic Nephropathy
    • Occurs in 20 to 40% of diabetics
    • Most common cause of ESRD
    • ESRD develops in 50% of type 1 patients with overt nephropathy within 10 years
    • ESRD develops in about 20% of type 2 patients with overt nephropathy within 20 years
    American Diabetes Association. Diabetes Care. 2007;30:S4-S41.
  • 78. Nephropathy: Diagnosis Category Spot Collection (albumin-to-creatinine) (mcg/mg) Normal < 30 Microalbuminuria 30 - 299 Clinical albuminuria > 300 Two of three specimens collected within a 3-6 month period should be abnormal before diagnosing . Exercise within 24 hr, infection, fever, CHF, marked hyperglycemia or HTN, pyuria, & hematuria may elevate urinary albumin excretion over baseline values American Diabetes Association. Diabetes Care. 2007;30:S4-S41.
  • 79. Nephropathy: Screening
    • Screening
      • DM 1: Within 5 years of diagnosis
      • DM 2: Upon diagnosis
      • DM 1 and 2: Follow-up exams annually
    • If (+) for microalbuminuria, test twice more over next 3 to 6 months
      • If 2 of 3 tests are positive, they have microalbuminuria and should have treatment started
    • Serum creatinine should be measured at least annually for estimation of GFR
    American Diabetes Association. Diabetes Care. 2007;30:S4-S41
  • 80. Nephropathy: Treatment
    • Glycemic control: HbA 1c < 7%
    • Blood pressure control: BP < 130/80 mmHg
      • ACE-I / ARBs
        • Decrease progression of microalbuminuria and slow rate of decline in GFR in patients with proteinuria
        • Non-DCCBs, BB’s, or thiazide acceptable if intolerant to ACEI/ARB
        • If ACE-I, ARBs, or thiazide used, monitor K +
    • Protein restriction
      • With presence of nephropathy
        • ≤ 0.8 g/kg per day ( ~ 10% of daily calories)
    American Diabetes Association. Diabetes Care. 2007;30:S4-S41
  • 81. Diabetic Neuropathy
    • Sensorimotor
    • Muscular
      • Muscle weakeness
      • Balance difficulties
    • Sensory
      • Pain
      • Parathesias
      • Numbness
      • Cramping
      • Nighttime falls
    • Autonomic
    • Cardiovascular
      • Syncope, fatigue, sustained heart rate
    • GI
      • Dysphagia, N/V, constipation, diarrhea
    • Genitourinary
      • ↓ bladder control, UTIs, ED, Dyspareunia
    • Sudomotor
      • Dry skin, calluses, limb hair loss
    • Endocrine
      • Hypoglycemic unawareness
    • Other
      • Depression, anxiety, sleep disorders
  • 82. Diabetic Neuropathy Screening
    • Annual foot exam:
      • Assessment for protective sensation, foot structure and biomechanics, vascular status, and skin integrity.
        • Neurologic status assessed with 5.07 (10-g) monofilament
        • Also consider: pin-prick sensation, temperature and vibration perception (using tuning fork)
        • Assess for history of claudication, and assess pedal pulses
        • Assess skin integrity especially b/w toes and under metatarsal heads. Look for erythema, warmth, or callus formation (increased plantar pressure)
        • Bony deformities, limitation in joint mobility, and gait and balance should be assessed
  • 83. Diabetic Neuropathy Treatment
    • Glycemic control: HbA 1c < 7%
    • Foot care
      • Proper footwear
      • Daily patient assessment
      • Moisturizing
        • Not between toes
      • NO bare feet!
  • 84. Peripheral Neuropathy Treatment
    • Optimal glycemic control: GOAL HbA 1c < 7%
    Wong M, et al. BMJ. 2007; 335; 1-10.
  • 85. Diabetic Retinopathy
    • Leading cause of new cases of blindness among adults (20 to 74 years of age).
    • Prevalence is strongly related to duration of diabetes.
    Normal Vision Diabetic Retinopathy
  • 86. Diabetic Retinopathy Screening
    • Comprehensive dilated eye exam:
      • DM 1: Within 3 to 5 years of diagnosis
      • DM 2: Upon diagnosis
      • DM 1 and 2: Follow-up exams annually
    American Diabetes Association. Diabetes Care. 2007;30:S4-S41.
  • 87. Diabetic Retinopathy Management
    • Tight glycemic control HbA 1C < 7%
    • Tight blood pressure control <130/80 mmHg
      • Both shown to delay or prevent onset of retinopathy
  • 88. Management Summary for Microvascular Complications Microvascular Complications Screening Nephropathy Neuropathy Retinopathy
    • Annual Exam:
    • Dilated Eye
    • Retinal vessels
    • Cataract
    • Intraocular Pressure
    • Annual Microalbumin:
    • Screen Albumin:
      • Creatinine ratio
      • Repeat to confirm
    • Comprehensive foot exam:
    • Inspection
    • Vascular
    • Vibratory perception
    • Monofilament
    Treatment
    • Glycemic Control
    • ACE-I / ARB
    • Glycemic Control
    • Foot care/ footwear
    • Medication Management
    • Glycemic Control
    • BP Control
    • Photocoagulation
    Everyone needs lifestyle modifications
  • 89. Standards of Care in Diabetes Diabetes Care. 2007;30(suppl 1):S4-S41
  • 90. Medical history during the 1 st evaluation
    • Age and characteristics of onset of diabetes
    • Eating patterns
    • History of diabetes education
    • Previous and current treatments
    • Exercise history
    • Hypoglycemic episodes
    • History of DKA?
    • History of diabetes related complications
  • 91. Physical Exam/Labs
    • Physical Exam
    • BP
    • Fundoscopic exam
    • Thyroid palpation
    • Skin exam
    • Peripheral pulses
    • Patellar and achilles reflexes
    • Peripheral sensation
    • Labs to order
    • A1C
    • Fasting lipids
    • LFTs
    • Microalbuminuria
    • SCr and GFR
    • TSH
  • 92. Health Maintenance/Prevention of Complications
    • Influenza vaccine annually
    • Pneumococcal vaccine for all adults
    • Smoking cessation!
    • BP at every visit, goal < 130/80 mmHg
    • Check lipids annually: Goal LDL <100 mg/dL, TG <150 mg/dL, HDL >40 for men >50 for women
    • Annual test for microalbuminuria
    • Annual eye exam to screen for retinopathy
    • Annual screening for peripheral and autonomic neuropathy
    • Foot care
  • 93. CASE 2
    • JT is a 58 year old male newly diagnosed with Type 2 diabetes
    • PMH
      • Dyslipidemia
    • SH: Tobacco 1 pack/day x 30 years; Rare ETOH use; denies illicit drug use; diet is high in carbohydrates and sugars and low in vegetables; physical activity “little to none”
  • 94. CASE 2
    • How much exercise should you recommend for JT?
    • A . 90 minutes/week
    • B . 60 minutes/week
    • C . 150 minutes/week
    • D . 300 minutes/week
  • 95. CASE 2
    • Which of the following should be done at diagnosis?
    • A . Eye exam
    • B . Test for microalbuminuria
    • C . Blood pressure
    • D . Fasting lipids
    • E . All of the above
  • 96. CASE 2
    • JT’s blood pressure is 150/90, what would be your recommendation for initial therapy?
    • A . Fosinopril
    • B . HCTZ
    • C . Diltiazem
    • D . Metoprolol