What is the best way to diagnose Diabetes? Dr David Lipscomb Consultant

Diabetes Care for You

What is Diabetes

• Diabetes is a complete or relative lack of insulin.

• First noted in 1552BC

• Diabetes (Greek) – siphon of water

• Mellitus (Latin) – honeysweet

• 11th Century detected by urine drinking

• 19th Century pancreas noted as the cause

WHO reports on classification 1965, 1980, 1985, 1998, 2006

Classification Four revised classifications (WHO 1999)

• Type 1

• Type 2

• Gestational

• Other – drug induced / pancreatic disease / MODY

• N.B. Roman numerals removed and Arabic used instead

Classic Onset Type 1

Age of

onset

Usually under 30

Usually 30 - 60

Usually over 30 years (except for MODY)

Present-

ation

Rapid onset of thirst, polyuria, weight loss

Gradual onset of milder symptoms

Often asymptomatic; may present with complications or gradual onset of symptoms. 85% obese. Part of Metabolic Syndrome.

Ketonuria

Usually present

May be absent

Absent (except with severe stress eg infection, infarction)

Anti-GAD

antibodies

Present in approx 80% at diagnosis

C-peptide

level

Low or absent, but may be low-normal initially (remission phase)

Normal-high (ie hyperinsulinemia)

Treatment

Insulin required urgently to prevent ketoacidosis

Insulin required, but not urgently

Healthy eating and exercise, may require oral agents, and/or insulin later

Classic Onset Type 1 Slow Onset Type 1

(LADA)

Type 2

Absent

Diagnosis of Diabetes

Diagnosis cannot be made from:

Blood glucose strips.

Urine testing

Glucose Tolerance Test 3 days of unrestricted diet and exercise

Evening meal as normal the night before

Overnight fast of 8-14 hours

TEST

Fasting blood on the morning

Drink 75g of anhydrous glucose in 250-300ml water over 5 mins

Blood sample 2 hours later

No smoking during the test

Goals and key findings

• International Expert Committee appointed by ADA, EASD, and IDF to consider current and future means of diagnosis of diabetes

• Committee convened in 2008 and reported in 2009

• Committee recommended use of HbA1c for diagnosis, based on

• Close correlation between HbA1c and diabetic retinopathy

• Improved instrumentation and standardization of HbA1c assay

• Less biologic variability, greater preanalytic stability of HbA1c versus glucose tests (FPG, OGTT)

• No requirement for pretest fasting

• Broad familiarity with HbA1c in diabetes management

• Committee recommended HbA1c diagnostic threshold of ≥6.5 % and preventive intervention when HbA1c is <6.5 % but ≥6.0 %

Prevalence of retinopathy by distribution of glucose and HbA1c

Prevalence of retinopathy by deciles of the distribution of fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), and HbA1c in Pima Indians

Recommendations of the International Expert Committee

For the diagnosis of diabetes:

• The HbA1c assay is an accurate, precise measure of chronic glycaemic levels and correlates well with the risk of diabetes complications

• The HbA1c assay has several advantages over laboratory measures of glucose

• Diabetes should be diagnosed when HbA1c is ≥6.5 %. Diagnosis should be confirmed with a repeat HbA1c test. Confirmation is not required in symptomatic subjects with plasma glucose levels >200 mg/dl (>11.1 mmol/l)

• If HbA1c testing is not possible, previously recommended diagnostic methods (e.g., FPG or 2hPG, with confirmation) are acceptable

• HbA1c testing is indicated in children in whom diabetes is suspected but the classic symptoms and a casual plasma glucose >200 mg/dl (>11.1 mmol/l) are not found

Recommendations of the International Expert Committee

For the identification of those at high risk for diabetes:

• The risk for diabetes based on levels of glycaemia is a continuum; therefore, there is no lower glycaemic threshold at which risk clearly begins

• The categorical clinical states prediabetes, impaired fasting glucose, and impaired glucose tolerance fail to capture the continuum of risk and will be phased out of use as HbA1c measurements replace glucose measurements

• As for the diagnosis of diabetes, the HbA1c assay has several advantages over laboratory measures of glucose in identifying individuals at high risk for developing diabetes

• Those with HbA1c levels below the threshold for diabetes but ≥6.0 % should receive demonstrably effective preventive interventions. Those with HbA1c below this range may still be at risk and, depending on the presence of other risk factors, may also benefit from prevention efforts

• The HbA1c level at which population-based prevention services begin should be based on the nature of the intervention, the resources available, and the size of the affected population

Local recommendations -

Diagnostic criteria for diabetes Routine cases and Non-

diabetic hyperglycaemia -

Diabetes NDH Normal

Hba1c mmol/mol 48 and above 42-47 41 or less

Fasting Plasma Glucose 7.0mmol/L and above 5.5-6.9 mmol/l 5.4 mmol/L or less

2hr Plasma Glucose in OGTT 11.1mmol/L and above 7.8-11.0 mmol/l 7.7 mmol/L or less

Random Plasma Glucose 11.1mmol/L and above

NDH= Non-diabetic hyperglycaemia Fasting = 8 hours or more without caloric intake (ADA 2018)

Which test is best ?

• National and international expert groups do not know. Relevant groups (WHO, ADA, UKDHADC, NICE) simply advise that HbA1c is now an option for diagnosing diabetes.

Pros and cons

• Benefits to using HbA1c for diagnosis

• No need for patient to fast

• More reproducible than glucose.

• Continuity with diabetes (once diagnosed, we switch from glucose to Hb1A1c, so it makes sense to use HbA1c for diagnosis)

• Disadvantages to using HbA1c:

• Inappropriate for some patients.

• We do not wish to be prescriptive. You may prefer fasting glucose, if simpler than assessing each patient’s suitability for diagnosis by HbA1c.

• Generally we recommend Hba1c.

Should a positive test be repeated?

• In the asymptomatic patient a repeat test is required, please repeat the same test as requested initially.

• National Guidance recommends a repeat test within 2 weeks of the first one.

• A diagnosis of Diabetes is only made is both results are at or above the diagnostic threshold.

• In the patient with classical symptoms of diabetes a repeat test is not required.

? Type 1

• Patients with suspected Type 1 Diabetes should be referred urgently to local level 4 Diabetes services in line with established pathways.

When not to use HbA1c to diagnose diabetes • 1.Rapid onset of diabetes – an increase

in HbA1c may not be detected until a few weeks later.

• a. Suspected type 1 diabetes – rapid onset of symptoms, weight loss, ketosis.

• b. Children – because most will have type 1 diabetes.

• c. Steroids. Antipsychotics & immunosuppressants can raise blood glucose, rarely precipitously

• d. After pancreatitis or pancreatic surgery.

• 2.Pregnancy. Multiple factors make HbA1c lower in pregnancy. The diagnosis of gestational diabetes should be made on blood glucose, in line with NICE guidance.

• 3.Conditions with reduced red survival may lower HbA1c:

• a. Haemoglobinopathy which will normally be detected by the lab, but should be suspected in racial groups where there is a high prevalence of sickle trait, sickle disease or thalassaemia.

• b. Haemolytic anaemia

• c. Severe blood loss

• d. Splenomegaly

• e. Antiretroviral drugs

• 4. Increased red cell survival may increase HbA1c e.g. splenectomy.

• 5. Renal dialysis patients have a markedly reduced HbA1c especially if treated with erythropoietin.

• 6. Iron and B12 deficiency and their treatment. May raise or lower HbA1c, but the effect is small.

What if you have glucose values and an HbA1c on a single patient?

Dealing with discordance in results

Many people identified as

having diabetes using A1C

will not be identified as

having diabetes by

traditional glucose criteria,

and vice versa.

When results of more than one test are available (FPG, A1C, 2hPG

in a 75-g OGTT) and the results are discordant, the test whose

result is above diagnostic cut-point should be repeated, and the

diagnosis made on basis of the repeat test.

FPG 2hPG

A1C

2018 Diabetes Canada CPG – Chapter 3. Definition, Diagnosis & Classification of Diabetes, Prediabetes, Metabolic Syndrome

A1C, glycated hemoglobin; FPG, fasting plasma glucose; OGTT, oral glucose tolerance test; PG, plasma glucose

Remission of diabetes

• A US Consensus (2009) defined Diabetes remission as –

• Partial Remission – Hyperglycaemia below diagnostic thresholds (ie Hba1c 42-47mmol/mol, FPG 5.5-6.9mmol/l) for 1 year or more without any active diabetes pharmacological therapy or ongoing procedures

• Complete Remission – Normal glycaemic measures (ie Hba1c <42mmol/mol , FPG 5.4mmol/l or less) for at least 1 year without any active diabetes pharmacological therapy or ongoing procedures

• Prolonged remission – Complete Remission of at least 5 years duration

Coding

• 'Diabetes resolved' (212H) should only be used if incorrectly coded as having diabetes and have never had diabetes.

• 'Diabetes in remission' (C10P) should be used as per 2016/17 General Medical Services (GMS) contract Quality and Outcomes Framework (QOF) Guidance for GMS contract 2016/17 (published April 2016)

Follow up -

• these people may still experience the macrovascular and microvascular complications of diabetes and therefore need continued monitoring.

• Patients coded 'diabetes in remission':

• a) are included in NDA audit

• b) will receive automatic invite for annual diabetes retinal screening

• c) need continued review for micro- and macro-vascular complications, ie. annual diabetes review checks, and for development of hyperglycaemia.

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