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acute pancreatic damage, HbA1c can lead to false-negative results. Another practical limitation is the lack of test availability in some parts of the world due to financial constraints. Guidelines agree that HbA1c ≥48 mmol/mol (≥6.5%) is diagnostic of diabetes, while the diagnosis of pre-diabetes uses two different cut-off values. The WHO criteria define pre-diabetes as HbA1c 42–47 mmol/ mol (6.0–6.4%), while the ADA recommends a wider range of 39– 47 mmol/mol (5.7–6.4%).5,7 Notably, the combination of HbA1c and fasting glucose in the diabetes range is diagnostic of diabetes and a second test is not required, even if the individual is asymptomatic. However, if the two are discordant, the number in the diabetes range should be repeated or, preferably, an OGTT performed, which remains the gold standard for diagnosing diabetes in unclear cases. The criteria used for diagnosing diabetes and pre-diabetes are summarized in Table 6. It should be noted that data from 73 studies on 294 998 individuals without known diabetes suggest that HbA1c is as good as or better than fasting, random, or post-load glucose levels for predicting CV risk.14

A diagram for the diagnosis of diabetes is shown in Figure 2.

3.2 Classifying diabetes

After abnormal glucose metabolism is diagnosed, the next step is to ascertain the type of diabetes in order to start the appropriate therapies (Supplementary data online, Table S2).

3.2.1 Type 1 diabetes

Type 1 diabetes constitutes 5–10% of individuals with diabetes and is secondary to destruction of pancreatic β-cells by an autoimmune process, with subsequent insulin deficiency. Recent guidance on diagnosing T1DM has been published.13 Briefly, individuals aged <35 years presenting with diabetes should be suspected of having T1DM, although this condition can occur at any age. A short history of osmotic symptoms accompanied by weight loss and raised glucose levels in a younger individual is highly suggestive of T1DM. Antibody testing helps to confirm the diagnosis, although this can be negative in 5–10% of individuals with T1DM, while C-peptide helps to assess endogenous insulin production in unclear cases (Supplementary data online, Table S2). Pancreatic β-cell function can partially recover after the diagnosis of T1DM, and this can last several years, often referred to as the ‘honeymoon period’. However, if this persists beyond 5 years, an alternative type of diabetes needs to be considered.15 Of importance, the combination of T1DM with insulin resistance, which can be referred to as double diabetes (DD), increases the risk of vascular complications, although the exact definition of DD is yet to be determined.16

3.2.2 Type 2 diabetes

Type 2 diabetes is the most common cause of diabetes (90% of the diabetes population) and is usually caused by insulin resistance coupled with ‘relative’ insulin deficiency, resulting in raised glucose levels. Individuals with T2DM can be asymptomatic and can be diagnosed after presenting with CV complications (Supplementary data online, Table S2). Therefore, it is mandatory to screen all patients with CVD for the presence of diabetes.

3.2.3 Monogenic diabetes

This comprises many mutations that cause glucose mishandling. A full description can be found elsewhere.17 Briefly, monogenic diabetes should be suspected in the presence of a strong family history of abnormal glucose metabolism in an autosomal dominant manner (i.e. successive generations with diabetes at a young age).17

Patients diagnosed with diabetes before the age of 6 months and those not fitting the T1DM or T2DM profiles should be suspected of having monogenic diabetes.

3.2.4 Secondary diabetes and stress hyperglycaemia

Diabetes can occur secondary to various conditions and therapies (Supplementary data online, Table S2). Stress hyperglycaemia is not uncommon in hospitalized patients and can occur in individuals with acute coronary syndrome (ACS) or HF.18 Stress hyperglycaemia without diabetes is associated with adverse in-hospital outcomes, and should be suspected in those with raised glucose levels during admission and normal HbA1c.19 Such individuals are best investigated using OGTT a few weeks after discharge to rule out diabetes or impaired glucose tolerance. Some studies suggest performing OGTT before hospital discharge but robust data supporting this approach are lacking.20,21

3.2.5 Gestational diabetes

Gestational diabetes mellitus (GDM) is defined as diabetes diagnosed in the second or third trimester of pregnancy that was not overt diabetes before gestation.7 While there is still no worldwide consensus regarding the best testing strategy, the ‘one-step’ 75 g OGTT, also recommended by the WHO, is the preferred test in many countries.22 In women with GDM, repeat testing is required in the postpartum period to rule out persistent abnormal glucose metabolism. Women with GDM will require lifelong annual diabetes screening given the high risk of developing diabetes.23–25 Also, evidence suggests that women with a history of GDM are at increased CV risk, even with normal post-partum glucose levels. Given that GDM is an important precursor of future cardiometabolic complications, women with a history of GDM should regularly be screened not only for diabetes, but also for CV health.26–29

3.2.6. Further sub-group classification of type 2 diabetes For information regarding further sub-group classification of T2DM, see Supplementary data online, Section 1.1.1.

3.3 Screening for diabetes

Criteria for diabetes testing differ widely across regions, and a comprehensive global screening programme is yet to be developed. It is generally agreed, however, that individuals in high-risk groups (those living with overweight or obesity, or having markers of insulin resistance, such as acanthosis nigricans or fatty liver disease) should be regularly screened, particularly after age 45 years. The ADA developed a relatively simple 7-point scoring system based on age, sex, weight, physical activity (PA), history of GDM, presence of hypertension, and family history of diabetes; it is advised that those scoring ≥5 are screened for diabetes.7 The prevalence of diabetes is increased among patients with CVD, with 23–37% of patients with ACS and 10–47% of patients with HF diagnosed with diabetes. This results in worse clinical outcomes compared with individuals with normal glucose metabolism.30–33 Therefore, individuals with ASCVD and/or HF and/or AF, particularly those admitted to hospital with an acute event, should be tested for diabetes; those with suspected stress hyperglycaemia (raised glucose levels

ESC Guidelines                                                                                                                                                                                          4059

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