Type 1 Diabetes and Insulin UG Classes.pptx

Definition : Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia resulting from impaired insulin secretion, insulin action [ insulin resistance ] or both .
The chronic hyperglycemia in DM is associated with long term damage dysfunction and failure of various organs
Is based on etiology not on type of treatment or age of the patient.
Type I(Beta cell destruction-absolute insulin deficiency)
Immune mediated Idiopathic
Type II
predominant insulin resistant with relative insulin deficiency
predominant secretory defect with insulin resistance

1. DIABETES MELLITUS TYPE 1 DR. SUDHIR BHANDARI MD, DNB, MNAMS, FRCP (London), FRCP (Edinburgh ) FELLOW AMERICAN COLLEGE OF ENDOCRINOLOGY (FACE) FELLOW AMERICAN COLLEGE OF PHYSICIANS (FACP) FELLOW INDIAN COLLEGE OF PHYSICIANS (FICP) FLLOW RESEARCH SOCIETY FOR THE STUDY OF DIABETES IN INDIA (FRSSDI) Senior Professor of Medicine Consultant-Internal Medicine, Diabetes & Endocrinology HON . PHYSICIAN TO H.E.THE GOVERNOR OF RAJASTHAN Vice Chancellor – Rajasthan University of Health Science, Rajasthan PRINCIPAL AND CONTROLLER- SMS HOSPITAL AND MEDICAL COLLEAGE, JAIPUR

2. The breakthrough: Toronto 1921 – Banting & Best

3. Diabetes mellitus Definition : D iabetes mellitus is a group of metabolic disorders characterized by hyperglycemia resulting from impaired insulin secretion, insulin action [ insulin resistance ] or both . The chronic hyperglycemia in DM is associated with long term damage dysfunction and failure of various organs

4. Types of Diabetes mellitus Type 1 DM Type 2 DM LADA MODY Gestational DM Secondary DM

5. New Classification (WHO) Is based on etiology not on type of treatment or age of the patient. Type I(Beta cell destruction-absolute insulin deficiency) Immune mediated Idiopathic Type II predominant insulin resistant with relative insulin deficiency predominant secretory defect with insulin resistance

6. Type 1 Diabetes Mellitus Formerly called insulin-dependent diabetes mellitus (IDDM) or juvenile diabetes T1DM is characterized by low or absent levels of endogenously produced insulin

7. Risk of development of Type 1 DM If mother has Type1DM risk in child is 2%. If father is affected risk is 7%. In a sibling of the index case is estimated as 6%. Risk is 6-10% in diazygotic twins & 30-65% in monozygotic twins

8. Beta Cells: S ecrete insulin . The Pancreas Alpha Cells: secrete glucagon Autoimmunity occurs in islet of Langerhans against the beta cells...

9. CLINICAL PRESENTATIONS DKA ( most common presentation in pediatrics) Classical symptom triad: polyuria, polydipsia and weight loss Accidental diagnosis

10. TREATMENT ELEMENTS Education Insulin therapy Glycemic control Monitoring Diet and meal planning Prevention and early dectection of complication

11. COMPLICATION S O F DIABETES Acute: DKA Hypoglycemia Hyperosmolar Coma Late-onset: Retinopathy Neuropathy Nephropathy Ischemic heart disease & stroke

12. Pathophysiology of type 1 DM Viral infection in a genetically susceptible individual triggers autoimmune destruction of beta cells Lymphocytic infiltration and progressive destruction of beta cells After 80-90% of beta cells are destroyed hyperglycemia develops and DM is diagnosed

13. Pathophysiology of type 2 Diabetes mellitus

14. Diagnosis of diabetes mellitus Fasting plasma glucose level of 126mg/dl or higher or A 2-hr plasma glucose level of 200mg/dl or higher during a 75 gm OGTT or A random plasma glucose of 200mg/dl or higher in a patient with classical symptoms HbA1c > 6.5%

15. Glycemic Goals Table 1.  Parameter Normal ADA Goals ACE/AACE Goals Fasting plasma glucose (mg/dL) < 100 90-130 < 110 Postprandial plasma glucose (mg/ dL ) < 120 < 180* < 140** A1C (%) 4-6 < 7*** ≤ 6.5 *1-2 hours post-meal **2 hours post-meal ***as close to normal as possible without undue risk of hypoglycemia

16. Actions of Insulin Liver ↑glucose uptake & glycogen synthesis Inhibits glycogenolysis & gluconeogenesis Muscle ↑glucose uptake & utilisation Inhibits proteolysis & AAs, pyruvate &lactate release Adipose tissue ↑glucose uptake and storage as fat & glycogen inhibits lipolysis & FFA+ glycerol release

17. How Is Insulin Normally Secreted?

18. The rapid early rise of insulin secretion in response to a meal is critical, because it ensures the prompt inhibition of endogenous glucose production by the liver disposal of the mealtime carbohydrate load, thus limiting postprandial glucose excursions.

19. When and why to start Absolute indications All type 1 DM Diabetic Ketoacidosis Serious infections During and after major surgery Pregnancy Failure to achieve control with 2 or 3 OHAs HbA1C >10 Kidney disease and liver disease Acute stroke ,MI

20. When and why to start Relative indications Micro and macrovascular complications Underweight or losing weight without dieting Symptoms from blood sugar >200mg/dl Any hospitalised patients On high dose steroids Onset of DM prior to 30 years or duration over 15 years

21. Why to start All type 1 DM Destruction of beta cells and absolute insulin defeciency Ketoacidosis Absolute or relative insulin deficiency ↑ counter regulatory hormones ↑ hepatic gluconeogeneis ,glycolysis &lipolysis lipid metabolised in liver  ketones Serious infections Gram – ve LPS  Insulin resistance Unable to ↑ endogenous insulin production Can precipitate DKA & HHS Insulin also prevents dehydration

22. Why to start During and after major surgery Metabolic stress response ↓ Insulin secretion ↑insulin resistance Excessive catabolic state Can precipitate DKA or HHS Pregnancy Teratogenecity Cross placenta  fetal hyperinsulinemia  macrosomia and fetal hypoglycemia Postprandial plasma glucose not addressed

23. Why to start Failure to achieve control with 2 or 3 OADDs ↓ β cell function  secondary failure HbA1C >10 , HbA1C>7.5 + FBS>250mg/dl ↓ glucotoxicity  β cell ,and on end organs Insulin can normalise any level of A1c Kidney and liver failure Metformin  acidosis Sulfonylureas  unpredictable can cause hypoglycemia OHAs Contraindicated in liver failure

24. Memories of Previous class…

25. Q. When the body does not respond to the insulin it makes, this is called... A. Type 1 diabetes B. Type 2 diabetes C. Both of the above D. None of the above B. Type 2 diabetes

26. Q. Gestational diabetes occurs... A During pregnancy B After a bout with shingles C At birth D After menopause A During pregnancy

27. Q. People with diabetes are prone to A Acne (Pimples) B Shingles C Infections D Migraine C Infections

28. Q. Keeping your diabetes under control early, will help you to prevent more health problems later. People with diabetes are at higher risk for which of these? Heart Disease Cancer Nerve Damage A and C D. A and C

29. Q. Type 1 Diabetes means: Insulin will be secreted in the body but cells cant utilise glucose Insulin will not be screted by body because of defect in pancreas Both A and B None B. Insulin will not be screted by body because of defect in pancreas

30. Q. Which of the following confirmed values meet the diagnostic threshold for diabetes? F asting blood glucose >140 mg/dl R andom glucose > 160 mg/dl 2 hour post prandial glucose ≥ 126 mg/dl F asting blood glucose ≥ 126 mg/dl D . Fasting blood glucose ≥ 126 mg/dl

31. Q. Which is not a symptom of diabetes? A Itchy skin B Thirst C Frequent urination D Muscle pain A Itchy skin

32. Q. The test for checking mean plasma glucose concentration over the previous 8-10 weeks is: Hemoglobin A1c Oral glucose tolerance test (OGTT) Fructosamine test Fasting plasma glucose concentration A. Hemoglobin A1c

33. Q. The pathogenesis of hyperglycemia in type 2 diabetes includes all the following mechanisms except for: Increased glucose production by the liver Impaired insulin secretion Decreased glucose uptake from the skeletal muscle All of the options given are correct D )   All of the options given are correct

34. Advantages of Insulin Therapy Oldest of the currently available medications, has the most clinical experience Most effective among the diabetic medications Can decrease any level of elevated HbA 1c No maximum dose of insulin beyond which a therapeutic effect will not occur Beneficial effects on triglyceride and HDL cholesterol levels Nathan DM et al . Diabetes Care 2006;29(8):1963-72.

35. Effect of Insulin on Triglyceride & HDL-C Levels Adapted from Nathan DM et al . Ann Int Med 1988;108:334-40. 1 1.1 1.2 1.3 1.4 1.5 Baseline Month 9 1 1.2 1.4 1.6 1.8 2 Baseline Month 9 Triglyceride Level (mmol/L) HDL-C (mmol/L) 1.85 1.17 1.51 1.39 HDL-C Triglycerides 0.3 mmol/L (27 mg/dL) p =0.07 n=15 0.2 mmol/L (8 mg/dL) p =0.07 n=15

36. Disadvantages of Insulin Therapy Weight gain ~2-4 kg 1 May adversely affect cardiovascular health Hypoglycemia 1 Rates of severe hypoglycemia in patients with type 2 diabetes are low in RCTs… 1 Type 1 DM: 61 events per 100 patient-years Type 2 DM: 1-3 events per 100 patient-years However, real-life rates may be higher 2-5 1. Nathan DM et al . Diabetes Care 2006;29(8):1963-72. 2. Henderson JN et al . Diabet Med 2003;20:1016-21. 3. Donnelly LA et al . Diabet Med 2005;22:749-55. 4. Akram K et al . Diabet Med 2006;23:750-6. 5. MacLeod KM et al . Diabet Med 1993;10:238-45.

37. Q. Type 1 diabetes is primarily treated with: Diet and exercise Stress management Insulin injection Sleep and exercise Insulin capsules C Insulin Injection

38. Which to start Types of Insulin Bovine and porcine insulin Human insulin Regular Neutral protamine Hagedorn [NPH] lente Insulin [ insulin zinc suspension] Protamine zinc Insulin [PZI] Insulin analogues Rapid acting : Lispro , Aspart , Glulisine Long acting : Glargine , Detemir , Degludec

39. Types of Insulin Rapid acting [Analogues] Lispro , Aspart , G lulisine Onset : 10-15 mins Peak : 60-90 mins Duration : 4-5 hrs Advantage : full biologic activity Less tendency for aggregation Decline of Insulin corresponds to decline of plasma glucose Can be taken just before meal Disadvantage : costlier

40. Q Which of the following is not an insulin analogue: Lispro Aspart Glargine Regular Insulin D Regular insulin

41. Safety issues with Insulin Analogues in GDM Ideal insulin Mimic physiological insulin secretion Does not cross placenta No mitogenic potential Since IgG bound insulin can cross placenta, therapeutic agent should not induce antibody generation

42. Q All of the followings are short acting insulin analogue except Lispro Aspart Glulisin Detemire D Detemire

43. Types of Insulin Short acting Insulin Regular Insulin Onset : 30-60 mins Peak : 2-4 hrs Duration : 5-8 hrs Disadvantages: Slow absorption and action Late peak & longer duration  post meal hypoglycemia Advantage : cheaper

44. Que. Regular insulin is used to Provide the diabetic with a baseline insulin level Increase blood glucose during a hypoglycemic episode Provide insulin to cover increased blood glucose associated with meals Help control blood glucose during the night C. Provide insulin to cover increased blood glucose associated with meals

45. Types of Insulin Intermediate acting NPH, Lente Onset : 1-3hrs Peak: 5-8hrs Duration: upto 18hrs Advantage : cheaper can be mixed Disadvantage : Significant peak More chances of nocturnal hypoglycemia

46. Types of Insulin Premixed Insulins One vial has fixed ratio of rapid or short acting and intermediate acting Insulin Ex : 70%NPH+ 30% Regular 75%NPH + 25%Lispro 50%NPH + 50% Regular 50%NPH + 50%Lispro 70% NPH + 30% Aspart Disadvantages: Donot allow independent dose adjustment Less flexible & Enforces rigid schedule Mixing may alter the absorption profile Advantage : simple to use

47. Types of Insulin Long acting Insulin analogues : Glargine , Detemir , Degludec Onset: 1.5-3hrs Peak: G largine , Degludec - No peak Detemir – dose dependent peak Duration: Glargine - 20-24 hrs ; Detemir – 9-24 hrs Degludec – 24 -40 hrs Advantages : later onset ,longer duration and less pronounced peak ↓ incidence of hpoglycemia Disadvantage: costly and cannot be mixed

48. Q Which of the following considered as peak less insulin Lispro Aspart Glargine Regular Insulin C Glargin

49. Degludec – A new basal insulin for adult patients with type 1 and type 2 diabetes

50. Half-life of insulin degludec is twice as long as that of insulin glargine Insulin degludec Insulin glargine 0.4 U/kg 0.6 U/kg 0.8 U/kg 0.4 U/kg 0.6 U/kg 0.8 U/kg Half-life (hours) 25.9 27.0 23.9 11.8 14.0 11.9 Mean half-life 25.4 12.5 *Insulin glargine was undectable after 48 hours Results from patients with type 1 diabetes IDeg, insulin degludec; IGlar, insulin glargine Heise et al. Diabetologia 2011;54(Suppl. 1):S425 * IDeg 0.8 U/kg IGlar 0.8 U/kg

51. Q Longest acting insulin is Detemir Degludec Glargine Regular Insulin B. Degludec

52. Newer & Emerging Insulin Theapies Ultra rapid acting Insulin Inhalable insulin[AFREZZA] Recently approved by FDA Inhaled dry powder that disso lves in lungs Action peaks : 15-20 mins Duration : 2-3 hrs Advantages : mimics very much natural insulin secretion less chance of hypoglycemia less weight gain Adverse effects : bronchospasm Contraindications : smokers , COPD , Asthma

53. Interactive discussion on contents and proposals for Module 2: Insulin Therapy in Inpatient Hyperglycemia Newer & Emerging Insulin Theapies Sl No. Insulin Type Clinical Trial Status Marketing Status 1 Fast Aspart Ultra Rapid Acting Completed Phase 3a NA 2 U-300 Basal Post Marketing Approved: USFDA, EU 3 Insulin PegLispro Basal Completed Phase 3 Awaiting Submission 4 Ly IGlar ( LY2963016) Basal Completed Phase 3 Approved: EU Awaiting Submission: USFDA 5 Transdermal Insulin Basal/Prandial Smart Patch Pre-Clinical Studies NA 6 Oral Insulin Oral Formulation development NA

54. Interactive discussion on contents and proposals for Module 2: Insulin Therapy in Inpatient Hyperglycemia Newer & Emerging Insulin Therapies; Contents 1. Faster-acting Aspart

55. Interactive discussion on contents and proposals for Module 2: Insulin Therapy in Inpatient Hyperglycemia Newer & Emerging Insulin Therapies; Contents 2. U-300

56. Newer & Emerging Insulin Therapies; Contents 3. Insulin PegLispro

57. Interactive discussion on contents and proposals for Module 2: Insulin Therapy in Inpatient Hyperglycemia Newer & Emerging Insulin Therapies; Contents 4. Ly IGlar (LY2963016)

58. Interactive discussion on contents and proposals for Module 2: Insulin Therapy in Inpatient Hyperglycemia Newer & Emerging Insulin Therapies; Contents 5. Transdermal Insulin

59. Newer & Emerging Insulin Therapies; Contents 5. Transdermal Insulin – Smart Patch

60. Newer & Emerging Insulin Therapies; Contents 6 . Oral Insulin – Approaches Challenges Approaches Challenges Approaches Kanzarkar M. Oral insulin-delivery system for diabetes mellitus. Pharm Pat Anal. 2015 Jan;4(1):29-36. doi : 10.4155/ppa.14.53.

61. How to start in type 1 DM Dose requirement : 0.5-1 u/kg Start with : 0.5-0.75 u/kg Multiple injection regimen : 50% of dose – long acting [basal ] 10-20% of dose at each meal – short acting [ bolus] Split mixed regimen : NPH and short acting Morning 2/3 rd of the dose Evening 1/3 rd of the dose

62. Q What is the insulin requirement in a 20 kg child with type 1 diabetes mellitus. -10 U 10-20 U 20-30 U 30-40 U B. 10-20 U

63. How to start in type 2 DM Continue regimen; check HbA 1c every 3 months If fasting BG in target range, check BG before lunch, dinner, and bed; depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range) Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA 1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin If HbA 1c ≤ 7%... Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg) Check FG and increase dose until in target range If HbA 1c  7%... Hypoglycemia or FG >3.9 mmol/L (70 mg/ dL ): Reduce bedtime dose by ≥4 units (or 10% if dose >60 units) Pre-lunch BG out of range: add rapid-acting insulin at breakfast Pre-dinner BG out of range: add NPH insulin at breakfast or rapid-acting insulin at lunch Pre-bed BG out of range: add rapid-acting insulin at dinner Continue regimen; check HbA 1c every 3 months Target range: 3.9-7.2 mmol/L (70-130 mg/ dL ) If HbA 1c ≤ 7%... If HbA 1c  7%... Nathan DM et al . Diabetes Care 2006;29(8):1963-72.

64. Step One: Initiating Insulin Start with either… Bedtime intermediate-acting insulin or Bedtime or morning long-acting insulin Insulin regimens should be designed taking lifestyle & meal schedules into account Nathan DM et al . Diabetes Care 2006;29(8):1963-72.

65. Step One: Initiating Insulin, cont’d Check fasting glucose & increase dose until in target range Target range: (70-130 mg/ dL ) Typical dose increase is 2 units every 3 days, but if fasting glucose (>180 mg/ dL ), can increase by large increments (e.g. 4 units every 3 days) Nathan DM et al . Diabetes Care 2006;29(8):1963-72.

66. If hypoglycemia occurs or if fasting glucose (70 mg/ dL )… Reduce bedtime dose by ≥4 units or 10% if dose >60 units Nathan DM et al . Diabetes Care 2006;29(8):1963-72. Step One: Initiating Insulin, cont’d

67. Q. Low blood sugar levels after meals may be caused by:  Incorrect carbohydrate counting  Too much mealtime insulin  Increased activity right before or right after the meal (that requires an insulin dose adjustment)  A high fat and/or high protein meal  All of the above E All of the above

68. If HbA 1c is <7%... Continue regimen and check HbA 1c every 3 months If HbA 1c is ≥7%... Move to Step Two… After 2-3 Months… Nathan DM et al . Diabetes Care 2006;29(8):1963-72.

69. Step Two Nathan DM et al . Diabetes Care 2006;29(8):1963-72. Continue regimen; check HbA 1c every 3 months If fasting BG in target range, check BG before lunch, dinner, and bed; depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range) Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA 1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin If HbA 1c ≤ 7%... Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg) Check FG and increase dose until in target range If HbA 1c  7%... Hypoglycemia or FG >3.9 mmol/L (70 mg/ dL ): Reduce bedtime dose by ≥4 units (or 10% if dose >60 units) Pre-lunch BG out of range: add rapid-acting insulin at breakfast Pre-dinner BG out of range: add NPH insulin at breakfast or rapid-acting insulin at lunch Pre-bed BG out of range: add rapid-acting insulin at dinner Continue regimen; check HbA 1c every 3 months Target range: 3.9-7.2 mmol/L (70-130 mg/ dL ) If HbA 1c ≤ 7%... If HbA 1c  7%...

70. Step Two: Intensifying Insulin If fasting blood glucose (FBG) levels are above target range, intensify insulin If FBG levels are in target range but HbA 1c ≥7%, check blood glucose before lunch, dinner, and bed and add a second injection : If pre-lunch blood glucose is out of range, add rapid-acting insulin at breakfast If pre-dinner blood glucose is out of range, add rapid-acting insulin at lunch (or NPH at breakfast) If pre-bed blood glucose is out of range, add rapid-acting insulin at dinner Nathan DM et al . Diabetes Care 2006;29(8):1963-72.

71. Making Adjustments Can usually begin with ~4 units and adjust by 2 units every 3 days until blood glucose is in range Nathan DM et al . Diabetes Care 2006;29(8):1963-72.

72. If HbA 1c is <7%... Continue regimen and check HbA 1c every 3 months If HbA 1c is ≥7%... Move to Step Three… After 2-3 Months… Nathan DM et al . Diabetes Care 2006;29(8):1963-72.

73. Step Three Nathan DM et al . Diabetes Care 2006;29(8):1963-72. Continue regimen; check HbA 1c every 3 months If fasting BG in target range, check BG before lunch, dinner, and bed; depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range) Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA 1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin If HbA 1c ≤ 7%... Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg) Check FG and increase dose until in target range If HbA 1c  7%... Hypoglycemia or FG >3.9 mmol/L (70 mg/ dL ): Reduce bedtime dose by ≥4 units (or 10% if dose >60 units) Pre-lunch BG out of range: add rapid-acting insulin at breakfast Pre-dinner BG out of range: add NPH insulin at breakfast or rapid-acting insulin at lunch Pre-bed BG out of range: add rapid-acting insulin at dinner Continue regimen; check HbA 1c every 3 months Target range: 3.9-7.2 mmol/L (70-130 mg/ dL ) If HbA 1c ≤ 7%... If HbA 1c  7%...

74. Step Three: Further Intensifying Insulin Recheck pre-meal blood glucose and if out of range, may need to add a third injection If HbA 1c is still ≥7% Check 2-hr postprandial levels Adjust preprandial rapid-acting insulin Nathan DM et al . Diabetes Care 2006;29(8):1963-72.

75. Stepwise Intensification of Treatment for Continuity of Control Progressive deterioration of  -cell function Lifestyle changes Oral agents Basal Add basal insulin and titrate Basal plus Add prandial insulin at main meal Basal bolus Additional prandial doses as needed FBG above target HbA 1c above target HbA 1c above target FBG at target HbA 1c above target Adapted from Raccah D et al . Diabetes Obes Metab 2008;10(2):76-82.

76. Insulin regimens Split mixed Regimen or premix consists of twice daily inj of NPH mixed with short acting insulin 2/3 rd in morning and 1/3 rd in evening Draw backs: Enforces rigid schedule on patient Does not generate near normal glucose control in type1 DM Does not mimic normal physiology Prone for hypo &hyperglycemia Advantage : simple

77. Q A 40 kg old insulin dependent patients want to take twice daily insulin, what is best regimen for his, if total insulin demand is equal to 30 Unit? Insulin mixtard (30/70) 10 U – 20 U Insulin mixtard (30/70) 15 U – 15 U Insulin mixtard (30/70) 20 U – 10 U Insulin Regular 20 U – 10 U C. Insulin mixtard (30/70) 20 U – 10 U

78. Insulin regimens Multiple daily injections Refers to the combn of basal insulin and bolus insulin Bolus dose is altered to accommodate SMBG results, anticipated food intake and physical acivity

79. Basal vs Bolus Insulin Basal insulin B olus insulin . takes care of fasting hyperg - - lycemia . Suppress hepatic glucose . Takes care of prandial production[ overnight hyperglycemia & intermeal ] . Storage of nutrients . Prevent protein and . Helps supress intermeal lipid catabolism hepatic glucose production . prevent ketosis . 10-20% of daily need at each dose .50% of daily needs

80. Q. Bolus Insulin refers to: Insulin for food Insulin for a high sugar Insulin for sleeping Both A & B D. Both A & B

81. Multiple daily injections Advantage : mimics physiological insulin secretion Allows flexiblity for meals Disadvantages: More insulin injections

82. Continuous subcutaneous insulin infusion [CSII] External ,programmable pump is connected to an indwelling subcutaneous catherter to deliver rapid acting insulin To the basal insulin infusion prandial insulin infusion is delivered based on patients instruction Benefits : Better control of sugar including HbA1c Reduced no of hypoglycemic episodes Disadvantages : blockage due to air bubbles difficult to learn for patients

83. Q. What type of insulin is used with an insulin pump? Rapid-acting analog insulin Intermediate -acting analog insulin Long-acting analog insulin Any insulin is fine Rapid-acting analog insulin

84. Q. The device shown in image used for? To hear music To burn fat For continuous glucose monitoring For stress monitoring For continuous glucose monitoring

85. New AACE_ADA consensus statement on inpatient glycemic control ICU Setting Insulin infusion preferred Starting threshold not higher than 180mg/dl Maintain BG 140-180 mg/dl < 110 NOT recommended [not safe] Non-ICU Setting Most patients : pre meal BG< 140mg/dl Random BG < 180mg/dl More stringent targets may be appropriate in stable patients Less stringent targets may be appropriate in comorbid condtns Scheduled S.c insulin with basal nutritional correct preferred over regular insulin sliding scale

86. Somogyi phenomenon Insulin induced hypoglycemia in late evening  counterregulatory hormone response early morning hyperglycemia Occurs in type 1DM , less common in type 2DM Cause : ill timed insulin, missed food, inadverent dose Atypical hyperglycemia in early morning that resists treatment with increased insulin doses Tretment : if nocturnal hypoglycemia is confirmed or highly suspicious  reduce bed time insulin

87. Dawn effect Surge of hormones that body produces daily around 4-5 a.m Diabetics don’t have normal insulin responses to adjust for this  early morning hyperglycemia Treatment : Early dinner in evening low carbohydrate dinner Adjusting the dose of insulin

88. Where to Give Insulin: On Target! KBN 2014 Inject into fat layer under skin Rotate sites Student should choose site Common sites: abdomen, thigh buttocks, upper arms Diabetes.org Safe at Schools

89. Insulin Injection Technique KBN 2014

90. Needle size does matter… KBN 2014

91. Insulin Care Guidelines Allow insulin you are injecting to come to room temperature before administering Always look at your insulin for particles or unusual color. If it looks different than normal, don’t use it! KBN 2014

92. Mark of caution in Insulin therapy Educate patient and attendants about hypoglycemia especially school going juveniles While using insulin vials match the unit concentration and syringe strength Needles should be changed after every two to three injections

93. WHAT!? Did you say INSULIN?! Barriers to the Use of Insulin

94. Patient Concerns About Insulin Fear of injections Perceived significance of need for insulin Worries that insulin could worsen diabetes Concerns about hypoglycemia Complexity of regimens

95. Help Patient Accept and Prepare for Insulin Therapy Address patient concerns Dispel fear by countering misconceptions Review rationale for insulin use Explain that insulin Can be incorporated into lifestyle Causes only modest weight gain Is a common course of treatment for this progressive disease Promise patient support and close follow-up Monitoring can prevent hypoglycemia Today’s technology can facilitate daily injections and readings

96. What we have in our pockets? Basal Insulins ( NPH,Glargine,Detemir & Degludec ) Bolus Insulins (Human Regular & Analogs) Premixed (Human 70/30,Analogs 30/70,25/75,50,50)

97. Schematic Time-Activity Curves for Selected Insulin Formu lations

98. Evidence-based guideline-derived treatment algorithm Diagnosis Lifestyle intervention then metformin HbA 1c 6.5 % Add sulfonylurea Meal-time + basal insulin + metformin ± thiazolidinedione Add insulin Start insulin Add thiazolidinedione* HbA 1c 6.5 % HbA 1c 7.5 % HbA 1c 7.0 % HbA 1c 6.5 % IDF. Global Guideline for Type 2 Diabetes. 2005 *Alternatively, start thiazolidinedione before sulfonylurea, and sulfonylurea later. intensify insulin

99. How should I start insulin therapy for my patients with Type 2 diabetes? According to the IDF Global Guideline for Type 2 Diabetes: Insulin is the most effective way of reducing hyperglycaemia Insulin can be started as a basal insulin alone or with premix insulin Start insulin when glucose control on maximum tablets >7.5 % (HbA1c) Begin at low dose but titrate up rapidly in first month IDF. Global Guideline for Type 2 Diabetes. 2005

100. ~2x Mortality Rate (%) Mean Glucose Value (mg/dL) Krinsley JS. Mayo Clin Proc . 2003;78:1471-1478. N=1826 ICU patients. 5 10 15 20 25 30 35 40 45 80-99 100-119 120-139 140-159 160-179 180-199 200-249 250-299 >300 ~4x ~3x Hyperglycemia and Mortality in the MICU

101. All Type 1 diabetics should be on a basal / bolus insulin regimen to control glucose while minimizing hypoglycemia 6-19

102. However over time, most type 2 diabetics will also need both basal and mealtime insulin to control glucose 6-19

103. Practical strategy to start insulin in type 2 DM Continue oral agents at the same dose (eventually reduce) Add single evening dose(5 -10 IU) for thin and (10-15 IU) for obese patients Adjust dose weekly 2-4 IU

104. Meal bolus insulin Exercise * The dose should be decrease by 30% for postprandial exercise of less than one hour, 40 % for 1-2 hours, 50 % for more than two hours Food * Insulin requirement approximately 1 unit of insulin per 15 g carbohydrate

105. Insulin Pump Therapy Continuous subcutaneous insulin infusion (CSII) via battery-powered pumps provides a closer approximation of normal plasma insulin profiles. It accurately deliver a small baseline continuous infusion of insulin, coupled with parameters for bolus therapy. The bolus insulin determined by amount of carbohydrate intake and blood sugar level

106. Thank you