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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

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