Читать книгу Handbook of Diabetes - Rudy Bilous - Страница 15

During the natural history of all forms of diabetes, the disease passes through a stage of impaired glucose tolerance (IGT), defined as a plasma glucose of 7.8–11.0 mmol/L (140–200 mg/dL) 2 hours after an OGTT (Figure 3.2). Impaired fasting glucose (IFG) is an analogous category based on fasting glucose levels, and is defined as a FPG of 6.1–6.9 mmol/L (110–126 mg/dL).

IGT and IFG are intermediate metabolic stages between normal glucose homeostasis and diabetes. They are both risk factors for future diabetes and cardiovascular disease, but the 2‐hour plasma glucose concentration is a particularly strong predictor of cardiovascular risk and mortality.

As with the glucose measures, several prospective studies that used A1C to predict the progression to diabetes as defined by A1C criteria demonstrated a strong, continuous association between A1C and subsequent diabetes. Based on numerous studies and meta‐analysis, it is now considered that A1C range of 5.7–6.4% (39–47 mmol/mol) as identifying individuals with prediabetes or with impaired glucose regulation IGR).

Figure 3.2 The relationship between 2‐hour plasma glucose and survival in patients with normal glucose tolerance, patients with IGT, those with newly‐diagnosed diabetes by OGTT, and those with known diabetes, as shown by the DECODE study (combining data from 13 European cohort studies). From Glucose tolerance and mortality: comparison of WHO and American Diabetic Association diagnostic criteria. The Lancet 354(9179), 617–621.

A proportion of patients with IFG, IGT and/or IGR (5‐10% per annum) will deteriorate metabolically into overt diabetes. Lifestyle modification (diet, exercise and weight loss) is the best approach to diabetes prevention for these patients.

For an OGTT, the subject is tested in the morning after an overnight fast, in the seated position. After taking a fasting blood sample, 75 g of glucose is given by mouth, often in the form of a glucose drink such as Lucozade (843 mL based on the new formulation of 8.9g/100ml of glucose). For children, the glucose dose is calculated as 1.75 g/kg. A further blood sample is taken at 2 hours, and the fasting and 2 hour glucose values are interpreted as in Figure 3.3.

Glycosuria (the presence of glucose in the urine) is responsible for the classic diabetic symptoms and was previously regarded as a diagnostic hallmark of the disease. Nowadays, it indicates the need to test blood glucose, but cannot be used to diagnose diabetes because of the poor relationship between blood and urine glucose (Figure 3.6). This is for several reasons: the renal threshold for glucose reabsorption varies considerably within and between individuals, the urine glucose concentration is affected by the subject’s state of hydration and the result reflects the average blood glucose during the period that urine has accumulated in the bladder. The average renal threshold is 10 mmol/L (i.e. blood glucose concentration above this level will ‘spill over’ into the urine), but a negative urine test can be associated with marked hyperglycaemia.

Figure 3.3 Diagnosis of diabetes and IGT by the oral glucose tolerance test.

Longer term indices of hyperglycaemia include the HbA1c, a measure of integrated blood glucose control over the preceding few weeks. HbA1c is used primarily to assess glycaemic control among people with diabetes on treatment. HbA1c analyses are now being calibrated to the IFCC assay. Thus the units of HbA1c in many countries have changed from percent to mmol/mol (Table 3.3).

Table 3.3 Historically, HbA1c has been reported in percentage values describing the proportion of haemoglobin that is glycated. The assay was aligned to that used in the Diabetes Control and Complications (DCCT) trial. The International Federation of Clinical Chemistry (IFCC) has now established a new reference system, and values will be reported in mmol HbA1c per mol haemoglobin without glucose attached. Conversion for HbA1c is shown below.

DCCT (%)	IFCC (mmol/mol)	DCCT (%)	IFCC (mmol/mol)
6.0	42	9.0	75
6.2	44	9.2	77
6.4	46	9.4	79
6.5	48	9.5	80
6.6	49	9.6	81
6.8	51	9.8	84
7.0	53	10.0	86
7.2	55	10.2	88
7.4	57	10.4	90
7.5	58	10.5	91
7.6	60	10.6	92
7.8	62	10.8	95
8.0	64	11.0	97
8.2	66	11.2	99
8.4	68	11.4	101
8.5	69	11.5	102
8.6	70	11.6	103
8.8	73	11.8	105

Figure 3.4 The prevalence of retinopathy in type 2 diabetes relative to the time of clinical diagnosis. Note the presence of retinopathy at diagnosis and the likely onset of retinopathy and diabetes some years before diagnosis. From Paisey. Diabetologia 1980; 19: 31 – 34.

The potential value of screening for diabetes is to facilitate early diagnosis and treatment. About 20% of newly diagnosed type 2 diabetic subjects already have evidence of vascular complications, such as retinopathy, the prevalence of which increases with diabetes duration. This suggests that complications begin about 5–6 years before a diagnosis is made, and that the actual onset of (type 2) diabetes may be several years before the clinical diagnosis.

Figure 3.5 High‐risk patients who should be screened annually for type 2 diabetes.

In most countries, there is no systematic screening policy for diabetes, yet there are estimates that up to 50% of patients with diabetes are undiagnosed. Ad‐hoc screening of high‐risk groups is becoming more common. The fasting plasma glucose is simple, quick, acceptable to patients and of low cost, but can miss those with isolated post‐challenge hyperglycaemia and requires patient to be fasted. The OGTT is more difficult to perform, impractical for large numbers and expensive, but is the only way to identify post‐load hyperglycaemia. Screening should focus on high‐risk groups. HbA1c is widely used to screen individuals at high risk of developing diabetes.

Figure 3.6 Classification of diabetes.

Figure 3.7 Using C‐peptide to confirm type 1 diabetes based on residual beta cell function. MMT‐mixed meal tolerance test – i.e. patients ingested a standardized breakfast ingested over 10 min based on the total caloric need of the patient (25–30% of their daily caloric intake; 50% of the calories as carbohydrates). In routine practice this is utilised as a random ‘c‐peptide’ level.

Figure 3.8 Five replicable clusters of patients with diabetes.

Source: Adapted from Ahlqvist et al. Lancet Diabetes & Endocrinology, 1 March 2018.

Figure 3.9 Clinical features of type 1 and type 2 diabetes.

Figure 3.10 Other specific types of diabetes.