YIACO DM guidelines

Guidelines forDiabetes Mellitus diagnosis and monitoring: 

Guidelines for Diabetes Mellitus diagnosis and monitoring

Introduction: 

Introduction

Diabetes Mellitus: 

Diabetes Mellitus

ADA classification of Diabetes: 

ADA classification of Diabetes

Causes of Diabetes Mellitus: 

Type 1 Diabetes is caused by an activation of the immune system that causes destruction of the insulin producing cells (ß- islet cells) in the pancreas. Type 2 Diabetes is caused by two conditions: Insulin resistance as an inherited problem where the body needs more insulin to process sugar. Insulin resistance is most probably is a patho- physiological disorder at molecular level of receptor signaling. Insulin deficiency where the islet cells of the pancreas are unable to make enough insulin to overcome the resistance. Causes of Diabetes Mellitus

Type 1 Diabetes Mellitus : 

Type 1 Diabetes Mellitus

Type 2 Diabetes Mellitus : 

Type 2 Diabetes Mellitus

Gestational Diabetes Mellitus: 

Gestational Diabetes Mellitus

Natural History of Type 2 Diabetes: 

Natural History of Type 2 Diabetes 10 Type 2 diabetes Years from diagnosis 0 5 -10 -5 10 15 Pre-diabetes Onset Diagnosis Genetic predisposition

Diabetic Complications: 

Diabetic Complications Glycation is a process of non enzymatic reaction of active carbonyl group of a sugar or any carbonyl compounds with the amino group of N-terminal of a protein. Glycation occurs in 3 stages: Schiff base formation Amadorri arrangements Cross linked proteins & AGEs

 Glycation)The Maillard reaction(: 

Glycation )The Maillard reaction( Amine Lysine Arginine Sugar glucose fructose carbonyl compounds Shiff base unstable Glycated protein Amadori products Advanced Glycated End product AGEs** Quick reaction highly reversible … Amidori rearangement slow reaction poorly reversible + Early stages Latter stages No reversibility Protein crosslinking

Toxic effects of AGEs in DiabetesConsequences: 

Toxic effects of AGEs in Diabetes Consequences Retinopathy AGEs Macular oedema Ischemic retinopathy Capillary closure Neovessel (proliferative retinopathy) Nephropathy : Abnormal deposits of matrix material in glomerular mesangium ? glomerular volume ? Mesangial extracellular matrix ? Albumin and protein urinary excretion Angiopathy : predisposition to early atherogenesis arterial stiffness Systemic hypertension

Relationship of glycation marker (HbA1C ) to Risk of Microvascular Complications: 

Relationship of glycation marker (HbA1C ) to Risk of Microvascular Complications 14 Relative Risk (%) Retinopathy Nephropathy Neuropathy Microalbuminuria HbA1C (%) 15 13 11 9 7 5 3 1 6 7 8 9 10 11 12 Diabetes Control and Complications Trial (DCCT)

Slide15: 

Food AGE content ?g/100g Cereal 193,400 Cake 838,400 Duck skin 6959,000 Beverage AGE content ?g/250ml Orange juice 600 Tea 2025 Coffee 2200 Classic coca cola 8500 Diet Coke 9500 Koschinsky et al., 1997

Sources of Guidelines forDiabetes Mellitus : 

Sources of Guidelines for Diabetes Mellitus

Slide18: 

AACE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS ADA American Diabetes Association WHO World Health Organization NACB National Academy of Clinical Biochemists IDF International Diabetes Federation American College of Endocrinology (ACE)

Slide19: 

DCCT Diabetes Care and Complications Trial EDIC Epidemiology of Diabetes Interventions and Complication ACCORD Action to Control Cardiovascular Risk in Diabetes Study Sub Committees in Diabetes Studies

Health Disparities Collaborative – Diabetes: http://www.healthdisparities.net/collaboratives_diabetes.htm West Virginia Healthy People 2010 Objectiveshttp://www.wvdhhr.org/bph/hp2010/objective/contents.htmlMichigan Diabetes Programhttp://www.osophs.dhhs.gov/ophs/BestPractice/MI.htm American Diabetes Association http://www.diabetes.org/main/application/commercewf National Diabetes Education Program http://ndep.nih.gov/materials/puborder/resource.htm#health: 

Health Disparities Collaborative – Diabetes: http://www.healthdisparities.net/collaboratives_diabetes.htm West Virginia Healthy People 2010 Objectives http://www.wvdhhr.org/bph/hp2010/objective/contents.html Michigan Diabetes Program http://www.osophs.dhhs.gov/ophs/BestPractice/MI.htm American Diabetes Association http://www.diabetes.org/main/application/commercewf National Diabetes Education Program http://ndep.nih.gov/materials/puborder/resource.htm#health 20

Slide21: 

21 The American Association of Clinical Endocrinologists http://www.aace.com/clin/guidelines/ Preventive-Care Practices Among Persons with Diabetes from Morbidity & Mortality Weekly Report http://www.medscape.com/viewarticle/444031_2 Patient Diabetes Management Schedule http://publichealth.state.ky.us/Programs/Diabetes/Patient%20Diabetes%20Management-Schedule-patient.pdf

Slide22: 

22 Professional Diabetes Management Schedule http://publichealth.state.ky.us/Programs/Diabetes/Mgt-schedule-numbers-at-a-glance.PDF Diabetes Goal Contract http://www.healthdisparities.net/PatientGoalSetting.pdf National Data Facts http://publichealth.state.ky.us/diabetes-national-facts.htm

Guidelinesfor Diabetes Screening: 

Guidelines for Diabetes Screening

Screening for diabetes: 

Screening for diabetes

Screening for diabetes and risk factors: 

Screening for diabetes and risk factors

Slide26: 

Opportunistic screening:

Selective screening: 

Selective screening

Slide29: 

Testing for diabetes in asymptomatic children ? Overweight (BMI 85th percentile for age and sex, weight for height 85th percentile, or weight 120% of ideal for height) + any 2 of the following risk factors: ? Family history of type 2 diabetes in first or second-degree relative ? Race/ethnicity (Non- caucasian) ? Signs of insulin resistance or conditions associated with insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, or small-for gestational- age birth weight) ? Maternal history of diabetes or GDM during the child’s gestation Age of initiation for screening: age 10 years or at onset of puberty, if puberty occurs at a younger age Frequency: every 3 years Test: FPG preferred

Criteria for testing for pre-diabetes and diabetes in asymptomatic adult individuals: 

Criteria for testing for pre-diabetes and diabetes in asymptomatic adult individuals

Slide32: 

Criteria for the diagnosis of diabetes FPG =7.0 mmol/L (Fasting is defined as no caloric intake for at least 8 h.*) OR Symptoms of hyperglycemia +(random) plasma glucose = 11.1 mmol/L. Casual (random) is defined as any time of day without regard to time since last meal. The classic symptoms of hyperglycemia include polyuria, polydipsia, and unexplained weight loss. OR Post-prandial, 2-h plasma glucose = 11.1 mmol/L during an OGTT. The test should be performed as described by the WHO using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water.

Slide33: 

Diagnostic Criteria for Type 2 DM

Spotlights on Methodology of Glucose Measurement: 

Spotlights on Methodology of Glucose Measurement

Slide35: 

Sample of choice: Venous blood; whole blood, plasma or serum. Stability of specimen: at 20°C: decrease of 10-15 %/h at 4°C: decrease of 20 % in 24 h Stabilizer: NaF (6 g/L) + Oxalates EDTA + maleinimide Plasma/serum: at 20 °C: decrease of 15 % in 24 h Interferences: Anticoagulants, glutathione, ascorbic acid, a-methyldopa Pre-analytical effects: Posture, exercise, food ingestion, smoking,

Conversion factors between plasma and other vehicles for glucose values : 

Conversion factors between plasma and other vehicles for glucose values

Slide37: 

Enzymatic methods are accredited : hexokinase-G6PDH glucose dehydrogenase glucose oxidase (GOD) The enzymatic reference method for glucose on auto-analysers is the hexokinase/G6PDH method. The glucose dehydrogenase method has comparable analytical performance but less than 1% of lab use. The glucose oxidase methods performing slightly less well, since reducing substances may interfere with the peroxidase step. Modification of GOD method as done by amperometry (Abbott)

Slide39: 

The reference intervals of the three enzymatic methods for glucose in blood of fasting adults are: Serum/plasma Whole blood Hexokinase/G6PDH: 4.4 – 5.5 mmol/L 3.6 – 5.3 mmol/L Dehydrogenase: 4.4 – 5.5 mmol/L 3.6 – 5.3 mmol/L GOD/POD: 5.0 – 6.1 mmol/L 2.9 – 5.5 mmol/L CSF: 2.2 – 3.9 mmol/L Urine: < 0.83 mmol/L The concentration of glucose in cerebrospinal fluid is ~ 60 % of the plasma value. If CSF is contaminated with bacteria or additional cells, the glucose concentration may be much lower.

Slide41: 

pyruvate

Methods of HbA1c measurement : 

Methods of HbA1c measurement

Cation exchange chromatography: 

Cation exchange chromatography

Ion exchange HPLC: 

Ion exchange HPLC

Ion exchange HPLC: 

Ion exchange HPLC

Affinity chromatography: 

Affinity chromatography

Affinity HPLC: 

Affinity HPLC

Immune turbidmetric assays: 

Immune turbidmetric assays

Slide50: 

Shortened erythrocyte survival: Any condition that decreases mean erythrocyte age (e.g., recovery from acute blood loss, hemolytic anemia) will falsely lower GHB test results regardless of the assay method used.  Alternative forms of testing such as glycated serum protein (fructosamine) should be considered for these patients.

Comparative aspects of A1c assays: 

Comparative aspects of A1c assays *Coefficient of variation (CV).

Standardization of HbA1c: 

Standardization of HbA1c

Standardization of different assays: 

Standardization of different assays

Standardization of HbA1c assays: 

Standardization of HbA1c assays

NGSP standardisation scheme : 

NGSP standardisation scheme

NGSP standardisation scheme : 

NGSP standardisation scheme

Swedish standardisation scheme: 

Swedish standardisation scheme

International measurement system : 

International measurement system

Electrospray mass spectrometry (ES-MS): 

Electrospray mass spectrometry (ES-MS)

Electrospray mass spectrometry : 

Electrospray mass spectrometry

IFCC reference method : 

IFCC reference method

Relationship between IFCC & DCM: 

Relationship between IFCC & DCM

Relationship between IFCC & DCM: 

Relationship between IFCC & DCM

A1C & mean glycaemia : 

A1C & mean glycaemia

IFCC reference system : 

IFCC reference system

HbA1C & mean plasma glucose (DCCT): 

HbA1C & mean plasma glucose (DCCT) * Actual Mean blood glucose results are 10-15% lower.

Better A1C test ? Better diabetes care: 

Better A1C test ? Better diabetes care

Guidelinesfor Diabetic Nephrobathy: 

Guidelines for Diabetic Nephrobathy

Slide72: 

For values of A/C = 2.8 for females and = 2.0 for males the test should be repeated confirmed in 2 out of 3 measurements over 3 months Uncertainty is clarified by 24h urine for protein Microalbuminuria = 30 - 299 mg of albumin/24hrs

Albumin measurement in urine: 

Albumin measurement in urine

Guidelinesfor Diabetic Dyslipidemia: 

Guidelines for Diabetic Dyslipidemia

Dyslipidemia: 

Dyslipidemia

Dyslipidemia: 

Dyslipidemia

Guidelinesfor Gestational Diabetes: 

Guidelines for Gestational Diabetes

GDM: 

GDM

GDM: 

GDM

GDM: 

GDM

Treatment Goals for Diabetes Mellitus: 

Treatment Goals for Diabetes Mellitus :Guidelines

TREATMENT GOALS FOR DIABETES MELLITUS: 

TREATMENT GOALS FOR DIABETES MELLITUS Maintaining: Pre-meal blood glucose in the range of 5.0 mmol/L to 7.2 mmol/L Bedtime blood glucose in the range of 5.6 mmol/L to 7.8 mmol/L A hemoglobin A1c value from 6.5% (DCCT) to 7% (ADA) over 3 months

TREATMENT GOALS FOR DIABETES MELLITUS (Cont.): 

TREATMENT GOALS FOR DIABETES MELLITUS (Cont.) Maintaining: Blood pressure < 130/80 mm Hg LDL Cholesterol < 2.6 mmol/L, triglycerides < 1.7 mmol/L, and HDL cholesterol > 1.03 mmol/L in men (> 1.3 mmol/L in women) High risk cardiovascular patients should aim for LDL cholesterol < 1.81 mmol/L

Slide85: 

Do not use fructosamine as a routine substitute for HbA1c measurement; it may be useful where HbA1c is not valid.