In the Name of ALLAH, EverBeneficent, Infinitely Merciful
07/15/12   2
07/15/12   3
07/15/12   4
HOW TO DIAGNOSE              DIABETES?07/15/12                     5
TREATMENT TARGETS07/15/12                       6
Efficacy of Monotherapy in                                                 Type 2 Diabetes                      Agent     ...
Current FDA Approved        Combination Therapy Options in Type 2               Combination                               ...
Staged DiabetesManagement at IDC                                                                                          ...
Stages of Type 2 Diabetes—                                   UKPDS                         100                          75...
07/15/12   11
07/15/12   12
The Miracle of Insulin    Patient J.L., December 15, 1922   Februray 15, 192307/15/12                                     ...
UKPDS: decreased risk of diabetes-related complications                                                 associated with a ...
What are the anabolic effects of Insulin?Stimulates entry of amino acids into cells,enhancing protein synthesisEnhances ...
When should Insulin be used in       Type 2 diabetes mellitus?             “The Magnificent Seven”07/15/12                ...
When should Insulin be used in               Type 2 diabetes mellitus?       1. Type 2 diabetes not controlled with maxima...
When should Insulin be used in       Type 2 diabetes mellitus?    2. Type 2 diabetes during periods of physiological      ...
07/15/12   19
07/15/12   20
07/15/12   21
When should Insulin be used in            Type 2 diabetes mellitus?             3. gestational diabetes               Metf...
07/15/12   23
Indications of Insulin therapy?            4. Use of parenteral nutrition                or high-caloric supplements07/15/...
Indications of Insulin therapy?5. Diabetic ketoacidosis (DKA)/Hyperosmolar hyperglycemic nonketotic syndrome (HHNS)07/15/1...
Indications of Insulin therapy?  6. Progressive complications:     proliferative retinopathy/maculopathy,    progressive o...
Indications of Insulin therapy?           7. Chronic Renal Failure             For all above a creatinine of 4.0mg/dl     ...
Normal Pancreas                                            ‘Bolus’ Insulin                                            (Mea...
How does one classify the types of insulin?♦ Generally classified according to peak effect           and duration of actio...
What are the types of Insulin ?• Short acting                  : Regular insulin• Intermediate acting            NPH insul...
Insulin Time Action Curves                                       Rapid-Acting: Lispro (Humalog®), Aspart (NovoLog®),      ...
What are the types             of insulin regimens?• Premixed regimen• Split mix regimen• Basal bolus regime (multidose)• ...
Premixed insulin           AVAILABLE PREPRATIONS           • Premixed(30/70): Regular: 30 % NPH :             70%         ...
07/15/12   34
07/15/12   35
07/15/12   36
Basic Insulin Regimen:               Split-Mixed Regimen or                        Premix                             Endo...
Basic Insulin Regimen:               Split-Mixed Regimen or                        Premix                                 ...
Insulin Therapy Regimens  ♦Usual starting dose: 0.5-1.0 unit/kg/day07/15/12                                      39
Premixed insulin           • Dose adjustment:           • The fasting sugar depends on the             night dose of insul...
Self Monitoring is crucial                     Glucometers           At least 6-8 times a week ideally07/15/12            ...
Premixed insulin Advantages • more accurate dosing • lesser injections • Pen devices administer premixed forms Disadvantag...
Starting insulin in type 2 diabetes          - patient on full dose OHA           • Continue the OHA           • Start on ...
TIMING OF INJECTION• 70/30 30 MINUTES BEFORE  BREAKFAST AND SUPPER• NOVO MIX 70/30• HUMALOG MIX 25/75 5—15  MINUTES• BEFOR...
ADVANTAGES• SIMPLE AND EASY TO USE ;draw A  SINGLE DOSE OF A COMBINATION OF  INSULIN IN ONE SYRINGE• MINIMUM INSULIN DOSIN...
DISADVANTAGES• 70/30 INSULIN ;SHOULD WAIT 30  MINUTES AFTER INSULIN INJECTION  BEFORE EATING THE MEAL• FIXED RATIO OF INTE...
DISADVANTAGES• CAN NOT ADJUST REGULAR  INSULIN,INSULINASPART, OR INSULIN  LISPRO FOR VARIATION IN FOOD  INTAKE, BLOOD GLUC...
INDICATIONS• PATIENTS WITH LIMITED  CAPABILITIES• PATIENTS WHO ARE UNWILLING  TO INTENSIFY REGIMEN• INITIAL REGIMEN AFTER ...
07/15/12   49
STARTING DOSE• 2/3 TOTAL DAILY DOSE  BEFORE  BREAKFAST ,1/3  TOTAL DAILY DOSE  BEFORE SUPPER• 0.5—1.0 U/KG/DAY07/15/12    ...
Pre-mix (70/30)• Gaps in insulin coverage• Poor long-term control• Failure to match endogenous secretion pattern• Dawn phe...
Can Oral hypoglycaemic agentsbe continued at the same time with insulin?      •               Metformin         Best conti...
Can Oral hypoglycaemic agentsbe continued at the same time with insulin?           •                Sulphonylureas        ...
Summarizing……..Insulin administration is suitably as premixed fashion formost type 2 diabetes. Split-mix may be required i...
Aggressively Titrated                                    Premix                                 70/30+Met+Pio             ...
Comparison of Common                           Insulin Regimens*Variable                  Glargine*            NPH1     Pr...
Sunday, July 15, 2012   57
07/15/12   58
07/15/12   DR MAXUD DIABETOLOGIST   59
07/15/12   60
07/15/12           61
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Premix insulin regimens haffizabad 22 02 2012

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  • Slide 1-24 Stages of Type 2 Diabetes Epidemiological studies suggest that the onset of diabetes occurs 10 to 12 years before a clinical diagnosis is made. (Harris 1997) In the UKPDS study of type 2 diabetics, at least 50% of the patients had evidence of diabetic tissue damage when diabetes was first diagnosed. (UKPDS Study 16, 1995) In the earliest phase, when beta-cell function is not impaired, the ability of the beta-cells to hypersecrete insulin masks the impaired glucose tolerance, often for years. During the IGT phase, the FPG will be higher than the normal 110 mg/dL but lower than the 126 mg/dL that is indicative of diabetes. As beta-cell function continues to decline, mild postprandial hyperglycemia develops, reflecting the inability of the beta-cell to hypersecrete enough insulin to overcome insulin resistance. At the end of this prediabetic phase, the first phase of type 2 diabetes typically produces symptoms that lead to a diagnosis. During phase I, in the first 2 years after diagnosis of diabetes, beta-cell function decreases to between 70% and 40% of normal function. CORE
  • UKPDS 35 was a prospective observational study to determine the relationship between exposure to hyperglycemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes who were participants in the UKPDS. 3,642 white, Asian Indian and Afro-Caribbean UKPDS patients who had HbA 1c measured 3 months after their diabetes diagnosis and with complete data for potential confounders were included in the sub-analysis of relative risk. Reductions in the risk of microvascular and macrovascular complications that might be achieved by lowering HbA 1c by 1% were estimated. The incidence of clinical complications was found to be significantly associated with hyperglycemia. While any reduction in HbA 1c is likely to reduce the risk of complications, the lowest risk was observed in those with HbA 1c values in the normal range (< 6.0%). A 1% decrease in HbA 1c was estimated to correspond with significant reductions in any diabetes-related endpoint, diabetes-related death, all cause mortality, myocardial infarction, stroke, peripheral vascular disease, microvascular disease and cataract extraction. Stratton IM, et al. UKPDS 35. BMJ 2000; 321 :405–412.
  • This is Mr. M.C.’s left heel ulcer. Note the maggots infesting – but perhaps also debriding – this wound.
  • Slide 6-23 INSULIN TACTICS Twice-daily Split-mixed Regimens Twice-daily mixtures of NPH and regular insulins have been widely used for type 2 diabetes for many years. In some cases, premixed 70/30 insulin is used for this purpose. Patient profiles of insulin levels resulting from this method, as shown in this figure, do not come close to matching the normal endogenous secretory pattern, shown in the shaded background. Patients with type 1 diabetes using this “split-mixed” regimen rarely achieve reasonably good glycemic control by present standards, since they lack endogenous insulin to supplement the partially adequate profile of injected insulin. Type 2 diabetes patients who have substantial endogenous insulin may fare much better with this regimen, but may experience late morning or nocturnal hypoglycemia because of excessive levels of insulin at these times. Berger M, Jorgens V, Mühlhauser I. Rationale for the use of insulin therapy alone as the pharmacological treatment of type 2 diabetes. Diabetes Care . 1999;22(suppl 3):C71-C75; Edelman SV, Henry RR. Insulin therapy for normalizing glycosylated hemoglobin in type II diabetes: applications, benefits, and risks. Diabetes Reviews . 1995;3:308-334.
  • Slide 29 Twice-Daily Split-Mixed Regimens Twice-daily mixtures of NPH and regular insulins have been widely used for type 2 diabetes for many years Patient profiles of insulin levels shown in this slide do not come close to matching the normal endogenous secretory pattern seen in the shaded background Dawn phenomenon refers to the early morning fall of tissue insulin sensitivity counteracted by increased insulin secretion in nondiabetic individuals but manifested as rising glycemia in diabetic patients In some patients with marked dawn phenomenon, NPH insulin may be beneficial. Early morning hyperglycemia may also be managed by dividing the dose of NPH insulin between dinner and bedtime Berger M et al. Diabetes Care . 1999;22(suppl 3):C71-C75 Edelman SV, Henry RR. Diabetes Reviews . 1995;3:308-334
  • Slide 29 Twice-Daily Split-Mixed Regimens Twice-daily mixtures of NPH and regular insulins have been widely used for type 2 diabetes for many years Patient profiles of insulin levels shown in this slide do not come close to matching the normal endogenous secretory pattern seen in the shaded background Dawn phenomenon refers to the early morning fall of tissue insulin sensitivity counteracted by increased insulin secretion in nondiabetic individuals but manifested as rising glycemia in diabetic patients In some patients with marked dawn phenomenon, NPH insulin may be beneficial. Early morning hyperglycemia may also be managed by dividing the dose of NPH insulin between dinner and bedtime Berger M et al. Diabetes Care . 1999;22(suppl 3):C71-C75 Edelman SV, Henry RR. Diabetes Reviews . 1995;3:308-334
  • Patients are anxious when being started on insulin and when changes in therapy are made. This anxiety will block learning and memory. Always write down these directions for your patients What type(s) of insulin do you want them to take How much insulin do you want them to take When do you want them to take the insulin: If an injection is to be given before a meal-explain how long before the meal (30 minutes, 45 minutes etc.) Use large print, write legibly, and use a dark coloured pen (felt tip pens are a good choice).
  • Premix insulin regimens haffizabad 22 02 2012

    1. 1. In the Name of ALLAH, EverBeneficent, Infinitely Merciful
    2. 2. 07/15/12 2
    3. 3. 07/15/12 3
    4. 4. 07/15/12 4
    5. 5. HOW TO DIAGNOSE DIABETES?07/15/12 5
    6. 6. TREATMENT TARGETS07/15/12 6
    7. 7. Efficacy of Monotherapy in Type 2 Diabetes Agent HbA1c reduction Fasting glucose % Reduction (mg/dl) Sulphonylurea 1.5 - 2.0 60 - 80 Metformin 1.5 - 2.0 60 - 80 Pioglitazone 0.6 - 1.9 50 - 80 Alpha Gucosidase 0.5 - 1.0 20 - 30 inhibitor07/15/12 7 Bonnie Kimmel, MD and Silvio E. Inzucchi, MD Clinical Diabetes 23:64-76, 2005
    8. 8. Current FDA Approved Combination Therapy Options in Type 2 Combination Additional Additional Lowering of Lowering of FBG HbA1c (mg/dl) SU + MTF 1.5 – 2.0 60 – 80 SU + TZD 1.0 – 1.5 40 – 60 MTF + TZD 0.6 – 0.8 20 – 40 SU + AGI 1.0 – 1.5 20 – 40 07/15/12 8Bonnie Kimmel, MD and Silvio E. Inzucchi, MD Clinical Diabetes 23:64-76, 2005
    9. 9. Staged DiabetesManagement at IDC * 07/15/12 9Mazze, Strock, Simonson, Kendall, Cuddihy, Bergenstal. SDM Quick Guide 5th Edition, International Diabetes Center, 2009
    10. 10. Stages of Type 2 Diabetes— UKPDS 100 75 β-Cell Function (%) 50 IGT Postprandial Type 2 Type 2 Diabetes 25 Hyperglycemia Diabetes Type 2 Phase III Phase I Diabetes Phase II 0 -12 -10 -6 -2 0 2 6 10 14 Years From Diagnosis07/15/12 H. Diabetes Review. 1999;7:139. Lebovitz 10
    11. 11. 07/15/12 11
    12. 12. 07/15/12 12
    13. 13. The Miracle of Insulin Patient J.L., December 15, 1922 Februray 15, 192307/15/12 13
    14. 14. UKPDS: decreased risk of diabetes-related complications associated with a 1% decrease in A1C Observational analysis from UKPDS study datacorresponding to a 1% decrease in HbA1C Any Percentage decrease in relative risk diabetes- Diabetes- All Peripheral Micro- related related cause Myocardial vascular vascular Cataract endpoint death mortality infarction Stroke disease† disease extraction 12% 14% 14% * 19% 21% 21% ** ** ** ** ** 37% † Lower extremity amputation or fatal peripheral vascular disease 43% *P = 0.035; **P < 0.0001 ** 07/15/12 **Adapted from Stratton IM, et al. UKPDS 35. BMJ 2000; 321:405–412. 14
    15. 15. What are the anabolic effects of Insulin?Stimulates entry of amino acids into cells,enhancing protein synthesisEnhances fat storage (lipogenesis) and preventsmobilization of fat for energy (Lipolysis andKetogenesis)Stimulates entry of glucose into cells for utilization asenergy sourcePromotes storage of glucose as glycogen in muscle andliver cells (glycogenesis) 07/15/12 15
    16. 16. When should Insulin be used in Type 2 diabetes mellitus? “The Magnificent Seven”07/15/12 16
    17. 17. When should Insulin be used in Type 2 diabetes mellitus? 1. Type 2 diabetes not controlled with maximal doses of Oral Hypoglycaemic agents What do you mean by maximal doses of OHAs? Metformin 2500/3000mg a day + Glipizide 20mg/glibenclemide15-20mg/day Gliciazide 320mg/ Glimepride 6-8mg/day + Rosiglitazone 8mg/ Pioglitazone 45mg/day07/15/12 17
    18. 18. When should Insulin be used in Type 2 diabetes mellitus? 2. Type 2 diabetes during periods of physiological stress (surgery, infection) Continue OHAs simultaneously. Stop metformin in case of severe infections or impending reduction in renal perfusion07/15/12 18
    19. 19. 07/15/12 19
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    22. 22. When should Insulin be used in Type 2 diabetes mellitus? 3. gestational diabetes Metformin may be continued Discontinue other medications07/15/12 22
    23. 23. 07/15/12 23
    24. 24. Indications of Insulin therapy? 4. Use of parenteral nutrition or high-caloric supplements07/15/12 24
    25. 25. Indications of Insulin therapy?5. Diabetic ketoacidosis (DKA)/Hyperosmolar hyperglycemic nonketotic syndrome (HHNS)07/15/12 25
    26. 26. Indications of Insulin therapy? 6. Progressive complications: proliferative retinopathy/maculopathy, progressive or painful neuropathy For rapid control and tighter adjustment07/15/12 26
    27. 27. Indications of Insulin therapy? 7. Chronic Renal Failure For all above a creatinine of 4.0mg/dl Cutoffs for other OHAs:- Metformin: 1.5mg/dl Glimeperide/Glibenclemide: 2.0mg/dl Glipizide: 2.5mg/dl Pioglitazone/Rosiglitazone: 4.0mg/dl07/15/12 27
    28. 28. Normal Pancreas ‘Bolus’ Insulin (Meal Associated) Insulin Effect Basal Insulin (~0.5-1.0 U/hr) Insulin is released in response to varying blood07/15/12 glucose levels and hypoglycemia does not occur 28
    29. 29. How does one classify the types of insulin?♦ Generally classified according to peak effect and duration of action♦ Rapid acting/lispro /aspart/glulisine♦ Short acting: regular.♦ Intermediate acting: NPH.♦ Long acting(basal) lantus. /levimer.♦ Premixed:(30/70), (50/50), (75/25)07/15/12 29
    30. 30. What are the types of Insulin ?• Short acting : Regular insulin• Intermediate acting NPH insulin• Analogs rapid acting : Lispro, Aspart /glulisine Long acting : Glargine/levimer07/15/12 30
    31. 31. Insulin Time Action Curves Rapid-Acting: Lispro (Humalog®), Aspart (NovoLog®), Glulisine (Apidra®) Relative Insulin Effect Short-Acting: Regular (Humulin® R, Novolin® R) Intermediate: NPH (Humulin® N, Novolin® N) Long-Acting: Glargine (Lantus®) Detemir (Levemir®) 0 2 4 6 8 10 12 14 16 18 20 Time (Hours)Bergenstal, “Effective insulin therapy,” International Textbook of Diabetes Mellitusvol 1. 3rd ed, Chichester NY, John Wiley and Sons, Inc., 2004:995-1015. 07/15/12 31
    32. 32. What are the types of insulin regimens?• Premixed regimen• Split mix regimen• Basal bolus regime (multidose)• Bedtime dosing alone (NPH/Lente/Glargine)• Infusion07/15/12 32
    33. 33. Premixed insulin AVAILABLE PREPRATIONS • Premixed(30/70): Regular: 30 % NPH : 70% • Premixed (50/50): lispro 50% NPL 50% • Premixed Analogs Biphasic insulin aspart (30/70) 30% : Aspart 70% : protaminated aspart07/15/12 33
    34. 34. 07/15/12 34
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    37. 37. Basic Insulin Regimen: Split-Mixed Regimen or Premix Endogenous insulin Regular NPH B L D HS B07/15/12 37
    38. 38. Basic Insulin Regimen: Split-Mixed Regimen or Premix • Does not Endogenous insulin mimic normal Regular physiology NPH Hyperglycemia • Requires meal consistency • Snacking may result in weight gain • Hypo- and B L D HS B hyperglycemi07/15/12 a 38
    39. 39. Insulin Therapy Regimens ♦Usual starting dose: 0.5-1.0 unit/kg/day07/15/12 39
    40. 40. Premixed insulin • Dose adjustment: • The fasting sugar depends on the night dose of insulin • The post breakfast sugar depends on the morning dose of insulin • Rough calculation increase the insulin by one unit to reduce the sugars by 25mg/dl07/15/12 40
    41. 41. Self Monitoring is crucial Glucometers At least 6-8 times a week ideally07/15/12 41
    42. 42. Premixed insulin Advantages • more accurate dosing • lesser injections • Pen devices administer premixed forms Disadvantages • Fine tuning may not be possible • Strict meal pattern • Nocturnal hypoglycemia • May need “diet changes for insulin” rather than “insulin changes for diet”07/15/12 42
    43. 43. Starting insulin in type 2 diabetes - patient on full dose OHA • Continue the OHA • Start on insulin (approx 0.2-0.4 U/kg/day,morning 2/3, evening 1/3) • Reassess control with SMBG & titrate dosage07/15/12 43
    44. 44. TIMING OF INJECTION• 70/30 30 MINUTES BEFORE BREAKFAST AND SUPPER• NOVO MIX 70/30• HUMALOG MIX 25/75 5—15 MINUTES• BEFORE BREAKFAST AND SUPPER07/15/12 44
    45. 45. ADVANTAGES• SIMPLE AND EASY TO USE ;draw A SINGLE DOSE OF A COMBINATION OF INSULIN IN ONE SYRINGE• MINIMUM INSULIN DOSING THAT PROVIDES 24-HOUR INSULIN COVERAGE• HUMALOG MIX 75/25 INSULIN OR NOVO MIX 70/30 INSULIN CAN BE TAKEN 5-15 MINUTES BEFORE A MEAL07/15/12 45
    46. 46. DISADVANTAGES• 70/30 INSULIN ;SHOULD WAIT 30 MINUTES AFTER INSULIN INJECTION BEFORE EATING THE MEAL• FIXED RATIO OF INTERMEDIATE AND SHORT OR RAPID ACTING INSULIN MAY NOT CONTROL BLOOD GLUCOSE LEVELS• CAN NOT ADJUST INTERMEDIATE- ACTING INSULIN COMPONENT WITHOUT ADJUSTING THE SHORT OR RAPID ACTING INSULIN COMPONENT07/15/12 46
    47. 47. DISADVANTAGES• CAN NOT ADJUST REGULAR INSULIN,INSULINASPART, OR INSULIN LISPRO FOR VARIATION IN FOOD INTAKE, BLOOD GLUCOSE LEVELS OR EXERCISE• MUST TAKE INSULIN AND EAT MEALS ABOUT THE SAME TIME EVERY DAY MUST EAT ACONSISTANT AMOUNT OF CARBOHYDRATES AT EACH MEAL FROM DAY TO DAY• LEAST FLEXABLE OF ALL REGIMENS07/15/12 47
    48. 48. INDICATIONS• PATIENTS WITH LIMITED CAPABILITIES• PATIENTS WHO ARE UNWILLING TO INTENSIFY REGIMEN• INITIAL REGIMEN AFTER DIAGNOSES TO LEARN AND ADAPT TO INJECTIONS• TYPE 2 DIABETES07/15/12 48
    49. 49. 07/15/12 49
    50. 50. STARTING DOSE• 2/3 TOTAL DAILY DOSE BEFORE BREAKFAST ,1/3 TOTAL DAILY DOSE BEFORE SUPPER• 0.5—1.0 U/KG/DAY07/15/12 50
    51. 51. Pre-mix (70/30)• Gaps in insulin coverage• Poor long-term control• Failure to match endogenous secretion pattern• Dawn phenomenon• Increased glycaemia07/15/12 51
    52. 52. Can Oral hypoglycaemic agentsbe continued at the same time with insulin? • Metformin Best continued if renal function is normal. May reduce insulin requirements by 15-30%. • Adjunctive weight reducing effect • Thiazolidinediones • May be continued with insulin. • Can reduce insulin requirements from 15-60% • Major issue of weight gain, accentuated by insulin: 7.5%. 15%>5kg.07/15/12 52
    53. 53. Can Oral hypoglycaemic agentsbe continued at the same time with insulin? • Sulphonylureas • Glimeperide: doses of 2-4mg a day have a peripheral GLUT-4 activity reducing insulin requirement by 10-20%. • Glipizide and Glibenclemide can reduce insulin requirements by 5-15%. • Unpredictable- recommended previously in those with high C-peptide levels07/15/12 53
    54. 54. Summarizing……..Insulin administration is suitably as premixed fashion formost type 2 diabetes. Split-mix may be required in asubset.The neccessity of self blood glucose monitoring as aaccessory is emphasized. 07/15/12 54
    55. 55. Aggressively Titrated Premix 70/30+Met+Pio Met+PioBaseline A1C 8.1±1.0 7.9±0.9EOS A1C 6.5±1.0 7.8±1.2Percentage of Patients WithA1C (EOS)<7.0% 76.3 24.1≤6.5 59.1 11.5≤6.0 33.3 2.3≤5.5 14.0 0FPG (mg/dl) 130±50 162±41 07/15/12 55 Raskin et al. Insulin 2007;2 (suppl A):S11
    56. 56. Comparison of Common Insulin Regimens*Variable Glargine* NPH1 Premix2,3 Detemir4Efficacy Insulin WorksHypoglycemia† 1.0 1.4X 2.5-5.0X 1.0Insulin Dose 1.0 1.0 1.5-2.0X 1.6-2.1XWeight Gain 1.0 1.0 1.5X 0.7-1.0X* Normalized to glargine; sponsored comparator trials† Confirmed hypoglycemia1 Riddle MC et al. Diabetes Care 2003;26:3080-30862 Janka HU et al. Diabetes Care 2005;28:254-259 07/15/123 Raskin P et al. Diabetes Care 2005;28:260-265 564 Rosenstock J et al. ADA 2006; Abstract 555-P
    57. 57. Sunday, July 15, 2012 57
    58. 58. 07/15/12 58
    59. 59. 07/15/12 DR MAXUD DIABETOLOGIST 59
    60. 60. 07/15/12 60
    61. 61. 07/15/12 61

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