Diagnostic Criteria of Diabetes Mellitus Basil OM Saleh
Objectives 1. Definition 2. Terminology 3. Glycated Hemoglobin HbA1c 4. Normal Plasma Glucose Level Should be Defined ADA & WHO criteria 5. Criteria for Testing for Diabetes in Asymptomatic Adult Individuals 6.Tests to Diagnose Diabetes 7. Advantages and disadvantage of assays for glucose and HbA1c 8. Diabetes in children
Definition: The term diabetes mellitus (D M) describes several diseases of abnormal carbohydrate metabolism that are characterized by hyperglycemia. It is associated with a relative or absolute impairment in insulin secretion, along with varying degrees of peripheral resistance to the action of insulin.
D M is associated with reduced life expectancy and significant morbidity due to specific diabetes related microvascular & macrovascular complications. Every few years, the diabetes community reevaluates the current recommendations for the classification, diagnosis, and screening of diabetes, reflecting new information from research and clinical practice.
TERMINOLOGY The 1997 ADA Expert Committee introduced the terms type 1 and type 2 diabetes, and recommended against terms like insulin-dependent and noninsulin-dependent. Also "specific types gestational diabetes diabetes of genetic defects diseases of the exocrine pancreas & other endocrinopathies drugs
Glycated hemoglobin (HbA1c) reflects average plasma glucose over the previous eight to 12 weeks It can be performed at any time of the day and does not require any special preparation such as fasting. The use of HbA1c can avoid the problem of day-to-day variability of glucose values
It established a validated relationship between A1C and average glucose across a range of diabetes types and patient populations. HbA1c was introduced into clinical use in the 1980s and subsequently has become a cornerstone of clinical practice.
Recent estimates indicate there were 171 million people/world in 2000 with diabetes 366 million by 2030. Should normal plasma glucose levels be defined? ADA and WHO criteria ADA defined a normal FSG as 110 mg/dl in 1997 as 100 mg/dl in 2003 & a normal 2 h plasma glucose as <140 mg/dl.
The ADA diagnostic criteria for D M in 1997, with follow-up in 2003 and 2010. The diagnosis is based on one of four abnormalities: hemoglobin A1C (A1C) fasting plasma glucose (FPG) random elevated glucose with symptoms abnormal oral glucose tolerance test (OGTT); IFG and /or IGT high risk for D M.
The World Health Organization (WHO) has published guidelines for the diagnosis and classification of diabetes In 1965. These were reviewed in 1998. The 2005 consultation of WHO/IDF made the following recommendations: 1. The previous (1999) WHO diagnostic criteria should not be changed. 2. The diagnostic cut-point for IFG is 110 mg/dl should not be changed. 3. HbA1c should not be adopted as a diagnostic test
A report of WHO published in 2009 recommended that HbA1c can be used to diagnose diabetes: Diagnosis can be made if the HbA1c level is 6.5 %. Confirmation by repeat HbA1c measurement or symptoms and random plasma glucose levels >11.1mmol/l (200 mg/dl) are present..
Levels of HbA1c just below 6.5% may indicate the presence of intermediate hyperglycaemia. The precise lower cut-off point for this has yet to be defined, although the ADA has suggested 5.7 6.4% as the high risk range.
WHO recommended High risk of diabetes HbA1c (6.0 6.4%) Provide intensive lifestyle advice. Warn patients to report symptoms of diabetes. Monitor HbA1c annually. HbA1c <6.0% Some of these patients may still be at risk of diabetes. If clinically at high risk manage as above.
WHO Recommendation 2011 An HbA1c of 6.5% is recommended as the cut point for diagnosing diabetes. In patients without diabetes symptoms repeat venous HbA1c in the same lab within 2 weeks. If the second sample is < 6.5 % treat as high risk of diabetes and repeat the test in 6 months or sooner if diabetes symptoms develop.
A value of less than 6.5% does not exclude diabetes diagnosed using glucose tests. In symptomatic adults a single result 6.5 % will suffice. Situations where HbA1c must not be used as the sole test to diagnose diabetes.
All symptomatic children and young people Symptoms suggesting Type 1 diabetes (any age) Short duration diabetes symptoms Patients at high risk of diabetes who are acutely ill Taking medication that may cause rapid glucose rise e.g. corticosteroids, antipsychotics Acute pancreatic damage/pancreatic surgery. Moreover, Do not use HbA1c to diagnose diabetes in pregnancy.
Severe hyperglycaemia detected under conditions of acute infective, traumatic, circulatory or other stress may be transitory and should not in itself be regarded as diagnostic of diabetes.
Diagnosis & Classification of D M 2012(American Diabetes Association Clinical Practice Recommendations. Standards of medical care for patients with DM. January 2012 vol. 35 Supplement 1 S11-S63 ). Criteria for Testing for Diabetes in Asymptomatic Adult Individuals-Table 1
Diabetes Type Risk Factors Type 2 1. Testing should be considered for all adults who are overweight (BMI> 25 Kg/m2) and have additional risk factors: history of CVD first degree relative with D PCOS HDL-C< 35 mg/dl or TG 250 mg/dl HTN 140/90 or on meds A1c 5.7%, IGT or IFG delivered baby>9 Ibs, GDM habitual physical inactivity. 2. In the absence of the above risk, start testing for diabetes at age 45. 3. If results normal, repeat test at 3 year intervals or more frequently depending on risk Type 1 Type 1 prevention studies suggest that measurement of islet auto antibodies identifies individuals at risk for developing type 1 diabetes; those with prior transient hyperglycemia or those who have relatives with type 1 diabetes.
Tests to Diagnose Diabetes-Table 2 For all the below tests, in the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing
STAGE HbA1c FSG (No intake 8 hrs.) RSG (OGTT)75- g Diabetes A1c> 6.5 % FSG > 126 mg/dl RSG > 200 mg/dl plus symptoms Two-hour SG(2hSG) > 200 mg/dl Increased risk of Diabetes A1c 5.7-6.4 % IFG = 100-125 mg/dl IGT= 2hSG 140-199 mg/dl Normal A1c < 5.7 % FSG < 100 mg/dl 2hSG < 140 mg/dl
Recommendations For The Diagnosis And Classification Of Diabetes Mellitus 2012 GESTATIONAL DIABETES (GDM)
SCREENING TEST DIAGNOSIS CRITERIA At the first prenatal visit, screen for undiagnosed type 2 in those w/ risk factors as listed in Table 1 Standard Diagnostic Testing and Criteria as listed in Diagnosing Diabetes Table 2 Standard Diagnostic Testing and Criteria as listed in Diagnosing Diabetes Table 2 Screen for GDM at 24 28 weeks of gestation for all pregnant women not known to have diabetes. Screen women w/ GDM for diabetes 6-12 wks postpartum Perform a 75-g OGTT, with plasma glucose measurement fasting and at 1 and 2 h. The OGTT should be performed in morning after an overnight fast of at least 8 h. The diagnosis of GDM is made when ANY of following BG values are exceeded: Fasting 92 mg/dl 1 h 180 mg/dl 2 h 153 mg/dl
However there are 100-gr glucose load with plasma glucose measurement over 1 hr., 2 hr., and 3 hr. simple and first step evaluation of suspected GDM by 50-gr glucose load with PG estimation after 1 hr. without regarding to fasting state. Pregnant women are categorized as low, intermediate and high risk GDM.
Some of the factors that influence HbA1c and its measurement.
1. Erythropoiesis Increased HbA1c: iron, vitamin B12 deficiency, decreased erythropoiesis. Decreased HbA1c: administration of erythropoietin, iron, vitamin B12, reticulocytosis, chronic liver disease. 2. Altered Haemoglobin Genetic or chemical alterations in haemoglobin: haemoglobinopathies,hbf, 3. Glycation Increased HbA1c: alcoholism, chronic renal failure Decreased HbA1c: aspirin, vitamin C and E, certain haemoglobinopathies, 4. Erythrocyte destruction Increased HbA1c: increased erythrocyte life span: Splenectomy. Decreased A1c: decreased erythrocyte life span: 5. Assays Increased HbA1c: hyperbilirubinaemia, carbamylated haemoglobin, alcoholism, large doses of aspirin, chronic opiate use. Variable HbA1c: haemoglobinopathies. Decreased HbA1c: hypertriglyceridaemia.
Advantages and disadvantage of assays for glucose and HbA1c
Glucose HbA1c Patient preparation prior to collection of blood Processing of blood Stringent requirements if measured for diagnostic purposes. Stringent requirements for rapid processing, separation and storage of plasma or serum minimally at 4 C. None. Avoid conditions for more than 12hr at temperatures >23C. Otherwise keep at 4C (stability minimally 1 week). Measurement Widely available Not readily available worldwide Interferences: illness Severe illness may increase glucose concentration Severe illness may shorten red-cell life and artifactually reduce HbA1c values Haemoglobinopa -thies Little problem unless the patient is ill. May interfere with measurement in some assays.
Diabetes in children Diabetes in children usually presents with severe symptoms, very high blood glucose levels, marked glycosuria, and ketonuria. In most children the diagnosis is confirmed without delay by blood glucose measurements, and treatment
(including insulin injection) is initiated immediately, often as a life saving measure. An OGTT is neither necessary nor appropriate for diagnosis in such circumstances (glucose load is weight dependent; (1.75 g/kg).
The new criteria have simplified the diagnosis of diabetes and the ability to diagnose cardiovascular complications. Earlier diagnosis will increase the total number of people with diabetes, but if they are carefully managed, many of these new cases will be diet controlled. In the long term, complications should be lessened to the benefit of the individual and to the health service.
SUMMARY D M is a group of metabolic disorders of CHO metabolism in which glucose is underutilized, producing hyperglycemia. Diabetes and lesser forms of glucose intolerance, IGT and IFG, can now be found in almost every population in the world and epidemiological evidence suggests that, without effective prevention and control programmes, the burden of diabetes is likely to continue to increase globally
References Use of Glycated Hemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus. World Health Organization 2011. Definition and diagnosis and Classification of Diabetes Mellitus and its Complications Report of a WHO Consultation Part 1: Diagnosis and Classification of Diabetes Mellitus