Update New Treatments in Diabetes Sam Cataland MD Principles of Therapy Type 1 • Insulin administration • Education in self management and problem solving • Self monitoring of blood glucose SM

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Update New Treatments in Diabetes Sam Cataland MD Principles of Therapy Type 1 • Insulin administration • Education in self management and problem solving • Self monitoring of blood glucose SM Powered By Docstoc
					Update: New Treatments in Diabetes

                    Sam Cataland MD
    Principles of Therapy:
            Type 1

• Insulin administration
• Education in self-management and problem
  solving
• Self monitoring of blood glucose (SMBG)
• Appropriate diet
• Appropriate exercise regimen
             Principles of Therapy:
                     Type 2


•   Education in self-management
•   Medical nutrition therapy
•   Exercise
•   Weight reduction (if indicated)
•   Self monitoring of blood glucose
•   Oral agents
•   Insulin administration
             Available Therapies For
                Type 2 Diabetes
                                                           Metformin
                                                          reduces hepatic
                                                         glucose production
     Thiazolidinediones
          Insulin sensitizers




                                    Improved
                                Glycemic Control

                                                    Acarbose
                                                   slows digestion of.
 Sulfonylurea/                                       carbohydrates
 Repaglinide/                      Insulin
  Nateglinide                     Conventiional
Insulin secretagogues             vs analogues
MAJOR METABOLIC DEFECTS
   IN TYPE 2 DIABETES

• Peripheral insulin
  resistance in muscle
  and fat

• Decreased pancreatic
  insulin secretion

• Increased hepatic
  glucose output
                         Haffner SM, et al. Diabetes Care, 1999
Or T2DM
       Natural History of Type 2 Diabetes

                       Obesity    IFG*     Diabetes       Uncontrolled Hyperglycemia
                      350
                      300                           Post-meal Glucose
                      250
       Glucose
       (mg/dL)




                      200
                      150                                            Fasting Glucose
                      100
                       50

                      250
                                                                     Insulin Resistance
       Function (%)




                      200
         Relative




                      150
                                                                          Insulin Level
                      100              -cell Failure
                      50
                            -10   -5        0       5     10    15       20     25        30
*IFG = impaired fasting                             Years of Diabetes
glucose
Adapted from International Diabetes Center (IDC), Minneapolis, Minnesota.
   Physiologic Insulin Secretion
                 24-Hour Profile
                         Bolus Insulin
            50
 Insulin
(µU/mL)     25
             0                                           Basal Insulin
             Breakfast    Lunch     Dinner
           150
Glucose 100
(mg/dL)
         50
                                                    Basal Glucose
             0
                 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9
                    A.M.                  P.M.

                           Time of Day
       BASAL-BOLUS THERAPY
• Physiologic
• Attainment of goal HbA1c
• Potential reduction in cardiovascular
  morbidity with reduction in blood
  glucose excursion
            NEW INSULIN ANALOGUES
Insulin              Onset of      Peak Action   Duration of
Preparations          Action                       Action

Lispro/Aspart       5-15 minutes     1-2 hours      4-6 hours
(Humalog/Novolog)
   Bolus insulin
Glulisine               “               “              “
(Apidra)
   Bolus insulin
Glargine            1-2 hours         Flat        ~ 24 hours
(Lantus)
  Basal insulin
Detemir                 ?             Flat         ~ 14 hours
(Levemir)
  Basal insulin
   Effect of Dose of Humulin R and Humalog
       on Time-Action Profile in Healthy
           Humulin R
                     Volunteers
                             ®
                                                                          Humalog
                   (REGULAR insulin
           800     human injection, USP [rDNA            800                        0.30 U/kg (n=3)
                   origin]) 10 U                                                    0.20 U/kg (n=9)
           700                                           700
Glucose                                                                             0.10 U/kg (n=9)
 Infusion 600                                            600                        0.05 U/kg (n=6)
   Rate 500                                              500
(mg/min) 400                                             400
           300                                           300
           200                                           200
           100                                           100
             0                                             0
                    1   2    3     4   5   6    7    8            1   2   3     4   5    6   7
                                 Time/h                           8           Time/h


 sc, subcutaneous.
 Data from Woodworth JR, et al. Diabetes. 1993;42(suppl 1):54A.
Twice-daily Split-mixed Regimens


                                  Regular
                                  NPH
Insulin Effect




                 B   L   S   HS     B
                                     Glucose Infusion Rate
                                sc insulin                      n=20 T1DM
                                                                Mean ± SEM
                          4.0                                                           24

                                                                                        20
                          3.0                                   Ultralente




                                                                                             µ mol/Kg/min
                                                                                        16
              mg/Kg/min




                          2.0                                                           12
                                                                         CSII
                                                                                        8
                          1.0                                                Glargine
                                                                                        4
                                                                  NPH
                           0                                                            0

                                    0        4    8     12        16         20         24
                                                 Time (hours)

Lepore M. et al., Diabetes 49:2142-8, 2000
              Glargine Once Daily,
          Premeal Rapidly Acting Insulin

                                               Glargine
Insulin Effect


                 B      L        S        Hs              B
                                Meals

    Pros:                               Cons:
  • Postprandial control at each meal   • Inconvenient, multiple dosing
  • Improve fasting glucose             • Cannot mix insulins
  • Provides basal coverage
    throughout the day
     Treatment of T2DM

Exenatide a GLP-1 mimetic
        (Byetta)
Exenatide (Byetta) injectable GLP-1 mimetic
Exenatide (Byetta) GLP-1 mimetic
      Exenatide Versus Insulin Glargine in Patients with
      Suboptimally Controlled type 2 Diabetes
Changes in hemoglobin A1c level (top) and body weight (bottom)




              Heine, R. J. et. al. Ann Intern Med 2005;143:559-569
Self-monitored blood glucose profiles (top) and postprandial blood glucose
                  concentrations after test meal (bottom)




                  Heine, R. J. et. al. Ann Intern Med 2005;143:559-569
Inhaled Insulin (Exubera)
Inhaled Insulin Improves Glycemic Control When Substituted for or
Added to Oral Combination Therapy in Type 2 Diabetes
                Flow of patients through the study




             Rosenstock, J. et. al. Ann Intern Med 2005;143:549-558
Hemoglobin A1c values during 3 months of treatment (top) and patients reaching
             target hemoglobin A1c level at study end (bottom)
Adjusted mean change in fasting plasma glucose concentration (top) and 2-hour
postprandial glucose concentration (bottom) from baseline to study end after 12
                             weeks of treatment
Treatment-Related Adverse Events Experienced by More than 5% of Patients