مدیریت و کنترل دیابت نوع دو (Management of diabetes)
- 1. In the name of God
- 2. Basic principles Diagnosis and classification Management 2 Agenda
- 3. Management
- 4. 25. Why do some patients with prediabetes/early diabetes present with postprandial hypoglycemia? 4
- 5. How to manage? A 44-year-old obese male, was incidentally detected to have T2DM with fasting blood glucose 150 mg/dl and HbA1c 8%. He had no diabetes related complications. He insists on avoiding medications. “ Case 1
- 7. 26. What is the use of artificial sweeteners in the management of diabetes? 7
- 8. 27. Can exercise improve insulin sensitivity without weight loss? 8
- 9. 28. How to advice a patient with T2DM regarding exercise? 9
- 10. 29. Why is metformin considered as the first-line drug for the management of patients with T2DM? 10
- 11. 30. Mechanism of action 11
- 12. 31. Why metformin therapy is not associated with increased risk of hypoglycemia? 12
- 13. Should metformin be discontinued? A 44-year-old obese male with type 2 diabetes for 5 years is on therapy with metformin 500 mg twice a day, with fasting blood glucose 100 mg/dl, HbA1c 7.1% and serum creatinine of 1.6 mg/dl. “ Case 2
- 15. What to do next? A 62-year-old postmenopausal female with type 2 diabetes for 3 years, is on therapy with metformin 2 g/day, has HbA1c of 7.8%. She is skeptical of using sulfonylureas because of a previous hypoglycemic event. “ Case 3
- 17. What to do next? A 58-year-old male with T2DM for 3 years, is on therapy with metformin 2 g/day, has HbA1c of 8.7%. He has congestive heart failure and is fearful of insulin. Case 4 “
- 19. Drug class 19
- 20. 20
- 22. 32. What is the dosing schedule and time of administration of sulfonylureas? 22
- 23. 33. What should be the time of administration of antidiabetic drugs? 23
- 24. 34. What is the HbA1c-reducing efficacy of various treatment modalities in the management of diabetes? 24
- 25. What are the probabilities? A 58-year-old male well controlled (HbA1c 7.1%) with metformin, sulfonylurea, and pioglitazone presented with a history of sudden worsening of vision. Case 5 “
- 27. 35. Is the risk for bladder cancer with pioglitazone real? 27
- 28. 36. What are the differences between GLP1 agonist and DPP4 inhibitors? 28
- 29. 37. How is the insulin secretion stimulated by DPP4 inhibitors different from sulfonylureas? 29
- 30. 38. Why is therapy with DPP4 inhibitors/GLP1 analogues associated with low risk of hypoglycemia in patients with T2DM? 30
- 31. 39. What are the nondiabetic benefits of GLP1 analogues? 31
- 32. 40. Is there a risk of pancreatitis with incretin-based therapy? Suspected pancreatitis Not stablished reported Clinical trials Causality Discontinue 32
- 33. 41. Is there a risk of tumors with incretin therapy? Liraglutide rodents Thyroid C-cell tumors Human Relevance not determined 33
- 34. 42. What is the rationale of combining GLP1 agonists and basal insulin? 34
- 35. 43. What are SGLT2 inhibitors? if eGFR is <45 ml/min or if baseline HbA1c is <7.7% SGLT2i suppresses 30–40% loss of 300 Kcal (~75 g glucose) per day 35
- 36. 44. What are the characteristics of SGLT2 inhibitors? 36
- 37. 45. What are the unique features of insulin glargine? “peakless” long-acting acidic pH of 4 Micro precipitates in subcutaneous tissue Cannot be mixed with other insulins duration of action 18–24 h 10% of patients require twice daily usually basal insulin during night 37
- 38. 46. What are the concerns with the use of insulin glargine? insulin glargine is converted into metabolites, which has much lesser affinity for IGF1 receptor as compared to human insulin not supported by most meta-analysis and ORIGIN study supported by in vitro data Many observational studies: increased risk of cancer this risk has been refuted progression of diabetic retinopathy 38
- 39. 47. Which insulin is weight neutral? 39
- 40. 48. What are the characteristics of insulin detemir? 40
- 41. 49. How does insulin degludec differ from glargine? 41
- 42. 50. What is the utility of premixed insulin in the management of T2DM? 42
- 43. 51. When to initiate insulin in patients with type 2 diabetes at diagnosis? HbA1c >9% osmotic symptoms significant weight loss fasting plasma glucose >200–250 mg/dl ketosis/ket oacidosis Complication (infections, ACS, significant hepatic-renal dysfunction) 43
- 44. 52. What is Monnier’s hypothesis? HbA1C >10.2% HbA1C 7.3-10.2% HbA1C <7.3% 70% by post- prandial fasting = post- prandial 70% by fasting 44
- 45. 53. What should be targeted first in a patient with diabetes who have both fasting and postprandial hyperglycemia? Fasting Postprandial 45
- 46. What to do next? A 52-year-old man with type 2 DM of 8 year duration had FPG 170 mg/dl and HbA1c 8.9%. He is on metformin 2 g per day and glibenclamide 2 mg per day. Case 6 “
- 47. Answer, case 6 further increase in doses of sulfonylurea or metformin has only modest effects on glycemia The addition of DPP4 inhibitors, SGLT2 inhibitors or α-glucosidase inhibitors will decrease HbA1c only by 0.5–0.8% Addition of pioglitazone may not help to achieve target HbA1c in this individual addition of basal insulin, or long acting GLP-1 agonist Best option 47
- 48. 54. When to add basal insulin? It is ideal to add basal insulin as early as possible because T2DM is also an insulin-deficient state. Various studies have demonstrated that use of insulin in newly diagnosed T2DM even for 2–4 weeks resulted in early attainment of target HbA1c, stable glycemic control, and preservation of β-cell function over the next few years. In clinical practice, basal insulin is added either in second tier or third tier to control fasting hyperglycemia, especially if HbA1c is >8.5%. 48
- 49. 55. Who are the candidates for self-monitoring of blood glucose? Candidates All T1DM or T2DM on intensive insulin therapy Type 2 diabetes on less intensive insulin therapy All gestational diabetes 49
- 50. What to do next? A 57-year-old man was referred for glycemic management. He was diagnosed with type-2 diabetes 3 months prior by his primary care physician. HbA1 level of 9.7 % with a fasting plasma glucose of 258 mg/dL. Case 7 “ • Polyurea and polydipsia • Weight loss • Metformin ER 500 mg once daily • loose stools and bloating • Denies hypoglycemia • Body Mass Index 33.4 kg/m2 • Creatinine 1.0 mg/dL
- 51. 56. What Are Appropriate Glycemic Goals for This Patient? 51
- 53. What Are the Various Treatment Options for Newly Diagnosed Patients with Type-2 Diabetes? 53
- 54. If HbA1c above goal 54
- 55. • Past medical history: nephrolithiasis and cholecystectomy 8 years ago. • Family history: mother diagnosed with type-2 diabetes, his father had coronary artery disease at age 53. • He denies any history of tobacco or alcohol use. Current medications: aspirin 81 mg daily, hydrochlorothiazide 25 mg daily, metformin ER 500 mg once daily. Case 7 … “ Creatinine 1.0 mg/dL LDL 126 mg/dL Triglycerides 209 mg/dL HDL 37 mg/dL
- 56. 57. Should This Patient Be Screened for Cardiovascular Disease? Abnormal renal function Abnormal resting ECG Abnormal fundoscopic examination Cardiac symptoms Family history of premature coronary disease Modifiable risk factors such as elevated LDL cholesterol and obesity 56
- 57. 58. Should This Patient with an LDL Cholesterol of 126 mg/dL Be Treated? 57
- 58. 59. Should We Continue This Patient’s Low Dose Aspirin Therapy? 58
- 59. 60. What Are the Target Blood Pressure Goals for This Patient with Newly Diagnosed Type-2 DM? 59
- 60. 61. What Initial Clinical and Laboratory Evaluation Is Recommended for This Patient with Newly Diagnosed Type-2 Diabetes? 60
- 61. • A 65-year-old woman was diagnosed with diabetes 8 years prior to her presentation by routine blood work. She was initially started on metformin 500 mg twice daily at the time of diagnosis. Metformin dose was increased to 1,000 mg twice daily 3 years after diagnosis. • She had experienced good glycemic control until 1 year ago. HbA1c level was 6.8 % 1 year prior to this visit. The patient was feeling well. She denied polyuria, polydipsia, visual changes, or hypoglycemia or distal paresthesias. Case 8 “ Fasting blood glucose levels ranged from 170 to 190 mg/dL BMI 28.9 kg/m2
- 62. What to do next? Sulfonylurea DPP4i GLP-1 RA SGLT2i Meglitinide Insulin 62
- 63. 62. Oral antidiabetic agents? Generic name Dosage forms Starting dose Maximum dose Metformin 500, 1000 mg 500 mg qd 2000 mg qd Gliclazide Modified release 30, 60 mg Immediate release 80 mg 30 mg qd 80 mg BD 120 mg qd 320 mg/day Repaglinide 0.5, 1, 2 mg 0.5 mg TDS 4 mg TDS Sitagliptin 25, 50, 100 mg 100 mg qd 100 mg qd Linagliptin 5 mg 5 mg qd 5 mg qd Liraglutide 6 mg/ml 0.6 mg qd 1.8 mg qd Empagliflozin 10, 25 mg qd qd Pioglitazone 15, 30, 45 mg 15 mg qd 45 mg qd 63
- 64. 64 Which is better for this patient? Interaction Click the Interaction button to edit this object
- 65. 63. When to Consider Transitioning to Insulin Therapy? The United Kingdom Prospective Diabetes Survey (UKPDS) gradual worsening of glycemic control in type-2 diabetes result of progressive loss of insulin producing pancreatic beta cells need for insulin therapy after a diabetes duration of 10–15 years is common 65
- 66. 64. When insulin should be started in T2DM? 66
- 67. 65. How to start insulin in T2DM? 67
- 68. 66. Are patients on basal insulin attaining glycemic targets? 68
- 70. Types of insulin regimens 70 Insulin pump Multiple insulin injection regimen NPH/regular regimen
- 71. 69. Comparing long-acting analogue insulins over NPH insulin? NPH insulin Long-acting analogue insulins Nocturnal hypoglycaemia 71
- 72. 70. Premixed insulin? ① once daily dose 10 U/day once daily or 0.3-0.5 U/kg/day TDD < 20 U ② Twice a day if TDD >20 U titrate once or twice weekly Premixed insulin 72
- 73. 71. Premix human insulin vs. Premix analogue insulin? 73
- 74. 72. Regular insulin vs. rapid-acting insulins? The use of regular insulin generally discouraged less physiologic pharmacokinetic profile slower absorption longer duration of action inadequate prandial coverage late postprandial hypoglycemia 74
- 75. 73. Comparing the effects of basal insulins alone versus premixed insulin injections twice daily? 75
- 76. 74. How to calculate the insulin-to-carbohydrate ratio The 500 rule dividing 500 by the total daily insulin dose grams of carbohydrate covered by 1 unit of rapid-acting insulin 76
- 77. What are the probabilities? A 30-year-old woman with chief complaint of a “recurrent yeast infection.” Over the last several years, she has gained more than 10 Kg. She had excessive weight gain in pregnancy and her baby had to be delivered by cesarean because he weighed 4500 g. Family history is unknown. BMI = 31.6. Blood pressure is 140/90. Vaginal candidiasis was detected. Case 9 “
- 78. Question 1 and answer, case 9 Q1: What is the most likely primary diagnosis for this patient? A1: IFG or T2DM (fetal macrosomia, GDM or unrecognized T2DM) Q2. What physical findings are suggestive of this diagnosis? A2: Obesity, acanthosis nigricans, hypertension, candidal vaginitis 78
- 79. A 45-year-old man with diabetes since one years ago and 8- week history of progressive polyuria, polydipsia, fatigue, blurred vision, and an 4 kg weight loss. He was on metformin and sulfonylurea with BS 140 mg/dl by another physician. No FH of DM. BMI, 22.7, FPG 320 mg/dL, bicarbonate 14 mEq/L, LDL 82 mg/dL, HDL 60 mg/dL, and TG 56 mg/dL, serum ketone + Case 10
- 80. Question 1 and answer, case 10 Q1. What type of DM does the patient have? Type 1: Weight loss, lean body habitus, lack of FH of DM, lack of HTN, and dyslipidemia Type 2: Older age, more common overall, lack of ketoacidosis 80
- 81. Question 2 and answer, case 10 Q2. What is the final diagnosis? A2. Patient had positive anti-GAD antibodies. LADA = latent autoimmune diabetes in adults (T1.5DM). 81
- 82. An 8-year-old girl had hyperglycemia (715 mg/dL) and marked growth retardation (birth weight – 1650 g). She has been treated with insulin since birth. Diabetes-related antibodies have been undetectable on several occasions. Basal serum c-peptide concentrations were low at birth, declined further with age, and did not increase in response to glucagon. The girl has no evidence of diabetic complications. Her mother has IFG, and her father has IGT but neither parent is obese. Case 11
- 83. Question 1 and answer, case 11 Q1. What type of DM does the patient have? The patient is young and thin which favors T1DM. However, she has no evidence of autoimmunity and no reported episodes of DKA which favors T2DM. Next look at the family for evidence of T2DM. Both the mother and father have prediabetes, but neither is obese. This makes you wonder about T2DM. 83
- 84. Question 2 and answer, case 11 Q2. What tests could help distinguish between T1DM and T2DM? You might consider remeasuring autoantibodies if the panel was incomplete. C-peptide measurements are less helpful at diagnosis because c-peptide can be low in both new-onset T1DM and new-onset, uncontrolled T2DM. We are told that c-peptide measurements have declined over time so remeasuring them now is probably unnecessary. 84
- 85. Question 3 and answer, case 11 Q3. What is the most likely diagnosis? Most likely Dx is MODY. In this case you should send DNA for sequencing to determine the exact cause. MODY is a monogenic diabetes caused by mutations in the glucokinase enzyme gene or hepatocyte/ islet transcription factors. In the former case (MODY2), higher glucose levels are required to elicit insulin secretory responses, thus altering the set point for insulin secretion. In the latter case, several forms of MODY may be due to abnormal development of pancreatic β- cells. 85
- 86. Question 4 and answer, case 11 Q4. What tests could help distinguish between T1DM and T2DM? Most patients with MODY are treated with sulfonylurea drugs because it is principally a genetic problem in the pancreatic beta- cell. These agents are more or less effective depending on the exact cause of the disorder. 86
- 87. 68. The causes of secondary drug failure to Oral hypoglycemic agents? 87
- 88. References 88