Understanding Diabetes Jesse Omamogho

Transcription

1 Understanding Diabetes Jesse Omamogho 1 September 28, 2018

2 Disclosure No disclosures 2

3 About Me R&D Group Leader Bio-Rad, current Previous: Trinity Biotech, University College Cork, Ireland, Msc and PhD, Analytical Chemistry Current Work: NPD and Innovation HbA1c and Hb apathy Areas of expertise: Analytical method development Product innovation Chromatography 3

4 Format Divided into three sections Please ask questions Take breaks as needed 4

5 Outline At the completion of this session, the participant will be able to understand: The types, causes, symptoms, health complications and treatment of diabetes. The most common diabetes biomarkers for clinical practice. Advantages of testing HbA 1c for the screening and Diagnosis of Diabetes. 5

6 What is diabetes? Also referred to as diabetes mellitus A disease in which the body s ability to produce (Type 1) or respond (Type 2) to the hormone insulin is impaired, resulting in abnormal metabolism of carbohydrates and elevated levels of glucose in the blood and urine. 6

7 Staggering statistics 31.8M diabetics in India in year 2000, estimated to grow to 79.4M by 2030 (WHO) 7

8 Types of diabetes Type I Diabetes Type II Diabetes Gestational Diabetes LADA (Latent Autoimmune Diabetes of Adulthood) MODY (Maturity Onset Diabetes of the Young) NDM (Neonatal Diabetes Mellitus) 8

9 Type I diabetes (T1D) A chronic condition in which the β-cells from the islet of Langerhans in the pancreas gland produces little or no insulin to control sugar level in the body. Autoimmune destruction of the β-cell is the underlying cause of T1D 9

10 What is insulin? Insulin is a hormone made by the pancreatic Islet beta-cells. The insulin regulates glucose levels in the body. Glucose is an important energy source for cellular functions. 10

11 Pancreas and insulin production 11

12 Insulin is the key Cells in your body need sugar for energy, but sugar cannot get into most cells directly After a relatively high carb meal, your blood sugar rises. The β-islet cells in your pancreas produces insulin and released it into your bloodstream 12

13 Type I diabetes symptoms Can come on suddenly and progressively worsen Increased thirst Frequent urination Frequent hunger Bed-wetting (in children) Weight loss Irritability Fatigue and weakness Blurred vision 13

14 Type I diabetes symptoms 14

15 Contributing factors Genetic susceptibility Changing lifestyles High-calorie diets Sedentary lifestyle 15

16 Type I diabetes treatment Taking multiple dose of insulin (MDI) or insulin pump. Managing T1D with combination of CGM and Insulin pump significantly reduce the risk of complications. 16

17 Type II diabetes Metabolic condition where the body doesn t produce enough insulin or becomes resistant to it 17

18 Type II diabetes Most common form Can sometimes be controlled with diet and exercise Natural insulin production may be insufficient; insulin injections are then needed to sustain normal blood glucose levels 18

19 Type II diabetes More likely to develop Type II diabetes if: You are age 45 or older Have a family history of diabetes Are overweight or obese 19

20 Type II diabetes 20

21 Type II diabetes symptoms Signs and symptoms of Type II diabetes often develop slowly In fact, you can have Type II diabetes for years and not know it 21

22 Type II diabetes symptoms 22

23 Increased thirst and frequent urination Excess sugar building up in your body causes fluid to be pulled from the tissues This may leave you thirsty As a result, you may drink and urinate more than usual 23

24 Increased hunger Without enough insulin to move sugar into your cells, your muscles and organs become depleted of energy This triggers intense hunger 24

25 Weight loss Despite eating more than usual to relieve hunger, you may lose weight Without the ability to metabolize glucose, the body uses alternative fuels stored in muscle and fat. Calories are lost as excess glucose is released in urine 25

26 Fatigue If your cells are deprived of sugar, you may become tired and irritable 26

27 Blurred vision If your blood sugar is too high, fluid may be pulled from the lenses of your eyes This may affect your ability to focus 27

28 Slow-healing sores or frequent infections Type II diabetes affects your ability to heal and resist infections 28

29 Type II diabetes treatment Management Healthy eating Regular exercise Medication or insulin therapy Blood sugar monitoring. All these practices will help keep blood sugar level closer to normal, which can delay or prevent diabetes complications. 29

30 Healthy eating Recent Randomized Trial have shown eating lower carb high fat LCHF (ketogenic) diet help reduce or reverse type II diabetes. However, it s important to center your diet sourced from whole natural food. Fruits Vegetables Whole grains Eat very limited refined carbohydrates and sweets Work with a registered dietician can be used to help put together a meal plan. 30

31 Physical activity Exercise Daily walk Stay Active 31

32 Diabetes medications and insulin therapy MDI or Insulin pump (Type I and Gestational diabetes) Metformin (Type II diabetes) 32

33 Blood Sugar Monitoring Will be discussed in the next section 33

34 Type I vs. Type II diabetes 34

35 Type I vs. Type II diabetes 35

36 Gestational diabetes 36

37 What is GDM? Gestational diabetes mellitus (GDM) is recognized as a serious public health problem Babies high birth weight, birth defects Mothers complications at delivery, C-sections, future diabetes An estimated 5-10% of pregnant women suffer from GDM Risks to mother and newborn can be reduced if GDM is screened for, diagnosed and treated early Current standard of care for screening and diagnosing GDM suffers from high variability, poor accuracy, and inconvenience to the patient 37

38 Comorbidities 38

39 Comorbidities 39

40 Diabetes and heart attack 2/3 people with diabetes have high blood pressure People with diabetes are 2-4X likely to die of heart disease or have stroke than people who don t have the condition 40

41 Diabetes and heart attack 41

42 Diabetes and heart attack Connection starts with high blood sugar levels Over time, the high glucose in the bloodstream can damage arteries, causing them to become stiff and hard Fatty material can also build up on the inside of blood vessels (atherosclerosis); can eventually block blood flow to the heart or brain, leading to heart attack or stroke Risk of heart disease with diabetes is further elevated if you also have a family history of cardiovascular disease or stroke 42

43 Diabetes and heart attack People with diabetes develop cardiovascular disease at a much earlier age than others. Heart attack or stroke is the leading cause of death among people with diabetes. A person who has diabetes has the same risk of heart attack as someone who is not diabetic, but already had a heart attack. 43

44 Comorbidities 44

45 Diabetes and stroke People with diabetes are at increased risk have a stroke than people without diabetes Mortality is higher and post-stroke outcomes are poorer in patients with stroke with uncontrolled glucose levels 45

46 Diabetes and stroke Over time, excess sugar can contribute to the buildup of clots or fat deposits inside vessels that supply blood to the neck and brain- atherosclerosis As deposits grow, they can cause narrowing of blood vessel walls or a complete blockage When the blood flow to your brain stops for any reason, a stroke occurs 46

47 Comorbidities 47

48 Diabetes and eye disease Diabetic eye disease refers to a group of sightthreatening eye problems that people with diabetes may develop Glaucoma Diabetic retinopathy, damages the tiny blood vessels in the retina; most common diabetic eye disease Cataracts- clouding of the eye s lens that results in blurring of normal vision. People with diabetes 2X more likely to develop cataracts as other adults 48

49 Diabetes and eye disease 49

50 Diabetes and eye disease 50

51 Diabetes and eye disease 51

52 Diabetes and eye disease When glucose levels are not well controlled, sugar levels rise in the eye s lenses High glucose levels cause lens swelling Enzymes convert glucose into sorbitol in the lens, reducing clarity and increasing opaqueness Leads to cataract formation- makes things appear blurry, yellowish or faded, and increases glare 52

53 53 Diabetes biomarkers

54 Outlines: Major Key Biomarkers for Diabetes Monitoring and Diagnosis. 54

55 KEY BIOMARKERS 55

56 What is Biomarker? The term biomarker refers to a broad subcategory of medical signs that is, objective indications of medical state observed from outside the patient which can be measured accurately and reproducibly. Strimbu, K.; Tavel, J. A., What are Biomarkers? Curr. Opin. HIV AIDS 2010, 5 (6),

57 Types of Approved Biomarkers for diabetes Monitoring (sources) Direct Glucose (blood, interstitial fluid, urine) HbA1c (blood) Diagnosis HbA1c (Blood Red blood cells) G-Alb (Blood Serum/Plasma) 1,5-AG (Blood Serum) Glucose (OGTT/2-FPG) 57

58 Food for Thoughts Biomarkers are key component of disease management 58

59 Diabetes Biomarkers Diabetes Biomarkers and Disease Management 59

60 Diabetes Management Education 60 Quality Adjusted Life Year

61 Direct Glucose Measurement System-SMBG Blood glucose in the body is measured by glucose test strip/meter Self Monitoring of Blood Glucose (SMBG). 61

62 Glucose Measurement System-CGM Interstitial fluid glucose in the body is measured by continuous glucose monitor (CGM). 62 G6 TM (Dexcom) FreeStyle Libre TM (Abbott) Guardian Connect TM (Medtronic)

63 Benefits of SMBG/CGM Better control of glycemic variation for T1D Lower HbA1c on T1D patient than those not using CGM 1. CGM clinical benefits outweighs the cost with an ICER of $98,108 per QALY 2 1. Beck, R. W.; et al., Effect of continuous glucose monitoring on glycemic control in adults with type 1 diabetes using insulin injections: The diamond randomized clinical trial. JAMA 2017, 317 (4), Wan, W.; et al., Cost-effectiveness of Continuous Glucose Monitoring for Adults With Type 1 Diabetes Compared With Self- Monitoring of Blood Glucose: The DIAMOND Randomized Trial. Diabetes Care 2018, 41 (6),

64 HbA1c Most common practice in diabetes testing is the measure of blood glucose or glycated hemoglobin (HbA1c). 64

65 Difference between Blood Glucose and HbA1c Blood Glucose measurement provide a quick snapshot of your current glucose state. Very important for people on insulin dependent who regularly depend on MDI or Insulin pump. Very important to help prevent hypoglycemia. 65

66 Benefits of HbA1c and its measurement HbA1c is a measure of long term glycemic status. i.e. how well you ve maintained your blood sugar for the last 2 to 3 months. Elevated value of HbA1c indicates increased risk of developing complications. HbA1c is reported in % (NGSP) or mmol/mol (IFCC). 66

67 HbA1c and the status of RBC HbA1c is not recommended for: patient have low RBC turn-over. Patient who are on dialysis due to ESRD Patient with thalassemia disease. Anemia. 67

68 Glycated Albumin. G-Alb posses similar chemical structure as HbA1c. It reflects a shorter term glycemic status; suitable for postpariandial G-Alb is suitable under conditions that affect HbA1c. Recommended for gestational diabetes. 68

69 Characteristics of Glycated Albumin Glycated Albumin is a glycation product of Serum Albumin. Four main sites of glycation within the protein structure. 69

70 Using HPLC for HbA 1c Testing Tony Marquardt 70

71 Objectives Learn about current epidemiological landscape of Diabetes Learn why Hemoglobin A1c is important for managing Diabetes and current uses Learn about methods of measurement of HbA1c Learn about HPLC 71

72 Agenda The Challenges of Diabetes Why use HbA 1c for Diabetes testing HbA 1c Standardization Using HbA 1c to aid in Diagnosis of Diabetes HbA 1c Methods of Measurement HbA 1c Advantages of HPLC Missing one diagnosis is one too many 72

73 Diabetes The Challenges 73

74 Global Diabetes Prevalence by Region 2017 and 2045 estimates 74 Source: IDF Diabetes Atlas 8 th addition (2017)

75 75 Source: IDF Diabetes Atlas 8 th addition (2017)

76 Diabetes Estimates - Ranking 76 Source: IDF Diabetes Atlas 8 th addition (2017)

77 Diabetes Estimates - Mortality Globally Mortality is calculated from the relative risks attributable to diabetes 4.0 Million deaths every year 1 person dies every 8 seconds 77 Source: IDF Diabetes Atlas 8 th addition (2017)

78 Diabetes Estimates Expenditures Globally $727 USD Billion North America and Caribbean $377 USD Billion 78 Source: IDF Diabetes Atlas 8 th addition (2017)

79 Diabetes Why HbA 1c.? 79

80 DCCT and UKPDS Trials Diabetes Control and Complications Trial (DCCT) 1 and United Kingdom Prospective Diabetes Study (UKPDS) 2 Both showed excellent control as expressed by an HbA 1c < 7% where there was a marked reduction in complications of diabetes Both used Bio-Rad HPLC technology for HbA 1c testing 1 The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin dependent diabetes mellitus. The New England Journal of Medicine.1993;329(14): UKPDS (Type-2 Diabetes 2003)Ellenberg & Rifkind

81 DCCT Trial Diabetes Control and Complications Trial (DCCT) ( ) Multi-center, randomized clinical trial 1,441 Type 1 patients with diabetes participated Bio-Rad HPLC technology used for HbA 1c testing Subjects were randomly assigned to either intensive or conventional therapy Considered a landmark study 81 The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:

82 DCCT Trial 82

83 UKPDS Trial United Kingdom Prospective Diabetes Study (UKPDS) Summary: 83

84 DCCT Results 76% reduction in eye disease 50% reduction in kidney disease 60% reduction in nerve disease 84

85 DCCT Conclusion Showed therapy dramatically reduced risks for development and/or progression of chronic complications Benefit was directly related glycemic control using HbA 1c as an index 85 The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:

86 UKPDS Trial United Kingdom Prospective Diabetes Study (UKPDS) ( ) Clinical trial conducted at 23 centers within the UK 5,102 patients with Type 2 diabetes participated Bio-Rad HPLC technology used for HbA 1c testing Patients were monitored to see if the use of therapy lowers blood glucose levels 86 UKPDS (Type-2 Diabetes 2003)Ellenberg & Rifkind 2003

87 UKPDS Trial Results 21% reduction for deaths related to diabetes 14% for myocardial infarctions 43% for peripheral vascular disease 37% for microvascular complications 87 UKPDS (Type-2 Diabetes 2003)Ellenberg & Rifkind 2003

88 DCCT and UKPDS Trials Why HbA 1c? Bio-Rad Provided HPLC technology for HbA 1c testing FDA Recommended Measurement of Hemoglobin A 1c (HbA 1c ) is effective in monitoring long-term glycemic control in individuals with diabetes mellitus 88

89 HbA 1c Standardization 89

90 HbA 1c Standardization Organizations National Glycohemoglobin Standardization Program International Federation Clinical Chemistry and Laboratory Medicine Bio-Rad HbA 1c platforms are NGSP Certified whereas having traceability to the DCCT reference method Bio-Rad HbA 1c Calibrators are traceable to the IFCC reference method and reference materials 90

91 From Chaos to Order 91 Presented at AACC 2018 by Randi Little, NGSP

92 Diabetes Using HbA 1c to aid in Diagnosis 92

93 Undiagnosed Diabetes 93 Source: IDF Diabetes Atlas 8 th addition (2017) page 48

94 World Health Organization 2011 Guidance World Health Organization (WHO) HbA1c can be used as a diagnostic test for diabetes providing that: Stringent quality assurance tests are in place, and Assays are standardized to criteria aligned to the international reference values, and There are no conditions present which preclude its accurate measurement Source: Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus ( 94

95 American Diabetes Association 2018 Guidance DIAGNOSTIC TESTS FOR DIABETES To avoid misdiagnosis or missed diagnosis, the A1C test should be performed using a method that is certified by the NGSP and standardized to the Diabetes Control and Complications Trial (DCCT) assay. HbA1c assays can be used for: Monitoring Aid in diagnosing diabetes Aid in diagnosing prediabetes Suggested testing for children who are overweight or obese and have one or more additional risk factors 95 Source: American Diabetes Association (ADA) Source: Diabetes Care Volume 41, Supplement 1, January 2018.

96 HbA 1c Methods of Measurement 96

97 HbA 1c Target for Diabetes Management 97

98 Methods for HbA 1c measurement Structural based methods Enzymatic Immunoassay Boronate Affinity Charge based methods Capillary Electrophoresis Ion-Exchange (HPLC) 98

99 HbA 1c method characteristics 99 Pathology Consultation on HbA 1c Methods and Interferences Am J Clin Pathol. 2014;141(1):5-16. doi: /ajcpq23gttmlaevl Am J Clin Pathol American Society for Clinical Pathology

100 HbA 1c Structural based methods Enzymatic Boronate Affinity Immunoassay 100 Pathology Consultation on HbA 1c Methods and Interferences Am J Clin Pathol. 2014;141(1):5-16. doi: /ajcpq23gttmlaevl Am J Clin Pathol American Society for Clinical Pathology

101 HbA 1c Charge based methods HPLC Capillary Electrophoresis 101 Pathology Consultation on HbA 1c Methods and Interferences Am J Clin Pathol. 2014;141(1):5-16. doi: /ajcpq23gttmlaevl Am J Clin Pathol American Society for Clinical Pathology

102 HbA 1c Advantages of HPLC 102

103 Advantages of HPLC for HbA 1c Testing See the Difference with HPLC Not just a number! HbF Common Variants Uncommon Variants HPLC vs Structural methods New potential Interferences Biotin Lipemia 103

104 Advantages of HPLC for HbA 1c Testing Diabetic Result with Elevated HbA 1c Level HbA 1c = 10.6% 104 VARIANT II TURBO HbA1c kit 2.0 Instructions for Use LB rev B Dec 2016

105 Advantages of HPLC for HbA 1c Testing HbF Example HbA1c can be reported with HbF up to 25% High HbF can be Indicator for Hereditary Persistence of Fetal Hemoglobin HbF = 19.8% HbA 1c = 4.9% 105 VARIANT II TURBO HbA1c kit 2.0 Instructions for Use LB rev B Dec 2016

106 HbF Case Study Bio-Rad HPLC HbA1c = 6.9% HbF = 22.4% Initiate Treatment Same Sample Immunoassay HbA1c = 4.7% HbF =?? Undiagnosed 106

107 Advantages of HPLC for HbA 1c Testing Common Heterozygous Hemoglobin Variants Hemoglobin C Trait Hemoglobin D Trait 107 Hemoglobin E Trait Hemoglobin S Trait VARIANT II TURBO HbA1c kit 2.0 Instructions for Use LB rev B Dec 2016

108 Advantages of HPLC for HbA 1c Testing African Americans heterozygous for the common hemoglobin variant HbS may have, for any given level of mean glycemia, lower A1c by about 0.3% than those without the trait. 108 Source: American Diabetes Association (ADA) Source: Diabetes Care Volume 41, Supplement 1, January Page S15

109 Advantages of HPLC for HbA 1c Testing 109 Source: Randie R. Little et al. Effects of 49 Different Rare Hb Variants on HbA1c Measurements in Eight Methods. Journal of Diabetes Science & Technology. 2015:1-8.

110 Advantages of HPLC for HbA 1c Testing 110 Source: Randie R. Little et al. Effects of 49 Different Rare Hb Variants on HbA1c Measurements in Eight Methods. Journal of Diabetes Science & Technology. 2015:1-8.

111 Advantages of HPLC for HbA 1c Testing J. Baltimore 111 Source:

112 Advantages of HPLC for HbA 1c Testing Interferences Biotin HPLC is Biotin Free FDA Warning on Biotin Interference On November 28, 2017, the FDA posted a safety communication, alerting the public, health care providers, laboratory personnel and laboratory test developers that biotin can significantly interfere with certain laboratory test results which may go undetected in patients who are ingesting high levels of biotin as dietary supplements. The FDA has seen an increase in the number of reported adverse events due to biotin interference ucm htm

113 Advantages of HPLC for HbA 1c Testing Poster from Dr Yip 2018 AACC poster #309 Lipemia (Intralipid) interference Most immunoassays and the enzymatic method for HbA 1c are susceptible to negative interference from elevated triglycerides, while HPLC and Capillary Electrophoresis methods are resistant 113

114 Advantages of HPLC for HbA 1c Testing Bio-Rad HPLC - DCCT and UKPDS Trials - Bio-Rad HPLC method was the method of choice for HbA 1c testing - Chromatography shows more than just a number - HbF, Common and Uncommon Hemoglobin Variants - New studies are showing new interferences on other platforms - Bio-Rad has been using HPLC for Diabetes testing for over 30 years 114

115 HbA 1c Missing one diagnosis is one too many 115

116 Missing one diagnosis is one too many Video For more information regarding Bio-Rad HbA 1c : 116

117 Questions 117