The criteria for the diagnosis of diabetes recommended by the ADA in 2021 [1] and approved by the WHO [2] and the International Diabetes Federation (IDF) are shown in Table 1.

Table1. Criteria for the diagnosis of diabetes.

Diagnostic thresholds

 The thresholds for the diagnosis of diabetes are currently based on the glycaemic levels above which diabetes- related microvascular complications mostly occur. However, these thresholds have changed over time. The oral glucose tolerance test (OGTT) was first introduced by Hofmeister in 1889, but this was not standardized and various amounts of glucose with different two- hour thresholds were used throughout the 1960s and 1970s. The second WHO report published in 1980 [3] marked a breakthrough in harmonizing the diagnosis of diabetes. The report established that diabetes could be diagnosed with a casual plasma glucose of >11.0 mmol/l (200 mg/dl) or with a 75 g OGTT using fasting and two- hour thresholds of ≥8.0 mmol/l (145 mg/dl) and >11.0 mmol/l (200 mg/dl), respectively. The two- hour threshold was based on the observed risk of developing retinopathy in several populations, but there were less robust data for the fasting glucose thresh old, which was later revised to the current value of 7.0 mmol/l (126 mg/dl).

In the development of diabetes, there is a stage when the blood glucose values are above normal, but below the thresholds used for defining diabetes, which is termed pre- diabetes or inter mediate hyperglycaemia. Pre- diabetes encompasses abnormalities in fasting glucose (impaired fasting glycaemia) and two- hour post- glucose challenge glucose (impaired glucose tolerance, IGT). Both impaired fasting glycaemia and IGT increase the risk of developing diabetes, with approximately one- third of people with IGT developing type 2 diabetes; the annual incidence rate ranges between 2% and 10% depending on the population and the presence of risk factors [2]. Use of the term ‘pre- diabetes’ has been criticized on the basis that not all people with this condition progress to type 2 diabetes, and the term ‘intermediate hyperglycaemia’ is preferred by many. The diagnostic thresholds for pre- diabetes have also changed over time. The category of IGT was introduced by the WHO in 1965 and after a few iterations it was defined as a fasting glucose value of <7 mmol/l (126 mg/dl) and post- glucose value between ≥7.8 mmol/l (140 mg/dl) and <11.1 mmol/l (200 mg/dl) [4]. The 1997 ADA and 1999 WHO criteria defined impaired fasting glucose (IFG) as a fasting glucose value between ≥6.1 mmol/l (110 mg/dl) and <7.0 mmol/l (126 mg/ dl). In 2003, the ADA revised the lower cut- off value to ≥100 mg/dl (5.5 mmol/l). The reduction of normal fasting value to ≤100 mg/dl was partly to ensure that the prevalence of IFG was similar to that of IGT. Furthermore, many studies have shown that 5.6 mmol/mol (100 mg/dl) provides the best cut- point for predicting future diabetes and the level at which insulin secretion becomes abnormal. However, lowering this threshold significantly increases the prevalence of pre- diabetes, which has important personal and public health implications [5, 6]. As such, the WHO and other organizations did not adopt this change [5].

In 2011, glycated haemoglobin (HbA1c) was also introduced as a further diagnostic criterion for diabetes, with a threshold of 6.5% (48 mmol/mol) [7, 8]. The HbA1c test should be performed using the method certified by the National Glycohemoglobin Standardization Program or International Federation of Clinical Chemistry. A value of <6.5% (<48 mmol/mol) does not exclude diabetes diagnosed using glucose tests. The ADA report recognizes that individuals with an HbA1c between 5.7% and 6.5% are at risk of diabetes and includes HbA1c as a means of diagnosing pre- diabetes [8]. It should be noted that the risk of diabetes is continuous, can extend below the lower limit of the range, and is disproportionately greater at the higher end of the range [7].

Number of abnormal tests required

 In an individual with classic symptoms of hyperglycaemia, only one measurement of glucose or HbA1c above the diagnostic threshold is required to make the diagnosis. In the absence of a clear history of diabetes symptoms, however, the diagnosis of diabetes requires two abnormal test results from the same sample or in two separate test samples. Where there is uncertainty, the WHO and ADA recommend that a standard 75 g OGTT is used if possible in conjunction with HbA1c measurement. However, clinical practice is changing and in many high- income countries, where procedures for the accurate measurement of HbA1c are readily available, the OGTT is being used less and less frequently. In these settings, a single blood sample with measure of either fasting or random glucose and HbA1c is more commonly used for the diagnosis.

Further considerations of method of diagnosis

When used on a population basis, fasting glucose, two- hour glucose, and HbA1c identify slightly different groups of people as having diabetes. Thus, an individual may test positive for diabetes with one test but not another. As the OGTT combines both fasting and two- hour glucose, using fasting glucose alone will identify fewer people with diabetes than an OGTT. Studies in Asian populations [9] and the Diabetes Epidemiology: Collaborative analysis of Diagnostic criteria in Europe (DECODE) study [10] showed that if only fasting blood glucose was used, nearly one- third of cases with diabetes might be missed at diagnosis. There are similar concerns about HbA1c, but with time the groups coalesce to the point where all three tests become positive.

Analytical considerations

Blood glucose measurement has been the mainstay of diagnosis and monitoring glycaemic levels in diabetes for many decades. The OGTT is a comparatively inexpensive, sensitive index of hyperglycaemia including impaired glucose homeostasis. Standard enzymatic methods of glucose estimation are in widespread use.

However, high biological variability, poor reproducibility, and influence by acute factors such as stress, food, exercise, and some medications are the main disadvantages of using blood glucose. Moreover, precautions must be taken to reduce the lowering of sample glucose by glycolysis by adding anti- glycolytic agents, such as sodium fluoride. Despite this, the rate of decline in glucose con centration continues for up to four hours in small quantities. In addition, there are differences in glucose concentrations in whole blood, plasma and serum and between capillary and venous blood. The availability of point- of- care testing with glucometers has helped to reduce the disadvantages of blood glucose measurement to some extent. Moreover, rapid bedside measurements have also become possible with these meters.

HbA1c, initially identified as an index of chronic hyperglycaemia, has now evolved into a valuable tool to monitor glycaemic management, for screening and diagnosis of diabetes and pre- diabetes, and as a predictor of micro- and macrovascular complications [11, 12]. Presently the results are traceable to the Diabetes Control and Complications Trial (DCCT) assay values (measured as %) [13] and can also be compared to the highly accurate International Federation of Clinical Chemistry (IFCC) standardized values (mmol/mol) [11]. Measuring HbA1c has multiple advantages over blood glucose, but also has a few limitations, particularly in middle- and low- income developing countries (Table 2). Healthcare professionals using the test should be aware of these limitations and employ their discretion in interpreting the results [11, 14].

Table2. Advantages and limitations of using HbA1c.

References

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1. American Diabetes Association (2021). Diab. Care 44 (Suppl. 1): S15–S33.

2. World Health Organization (2019). Classification of Diabetes Mellitus. Geneva: WHO.

3. World Health Organization Expert Committee on Diabetes Mellitus (1980). Second Report. Tech. Rep. Ser. 646. Geneva: WHO.

4. Kumar, R., Nandhini, L.P., Kamalanathan, S. et al. (2016). World J Diab. 7: 396–405.

5. Shaw, J.E., Zimmet, P.Z., and Alberti, K.G. (2006). Diab. Care 29: 1170–1172.

 6. Borch- Johnsen, K., Colagiuri, S., Balkau, B. et al. (2004). Diabetologia 47: 1396–1402.

7. American Diabetes Association (2014). Diab. Care 37: S81.

8. Expert Committee Report on the Diagnosis of Diabetes (2009). Diab. Care 32: 1327–1334.

9. Wong, T.Y., Liew, G., Tapp, R.J. et al. (2008). Lancet 371: 736–743.

10. Balkau, B. (2000). Diab. Metab. 26: 282–286.

11. Sacks, D.B. (2005). Clin. Chem. 51: 681–683.

 12. Bennett, C., Guo, M., and Dharmage, S. (2007). Diab. Med. 24: 333–343.

13. The Diabetes Control and Complications Trial Research Group (1993). N. Engl. J. Med. 329: 977–986.

14. Bonora, E. and Tuomilehto, J. (2011). Diab. Care 34 (Suppl 2): S184–S190.

اخر الاخبار

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قسم العلاقات العامة يسلم دعوة الملتقى التربوي التنسيقي الثاني لتربية محافظة ذي قار

شعبة فاطمة بنت أسد تجري الاختبارات النهائية للمشاركات في دورة هدى للناس

قسم الشؤون الفكرية يصدر الجزأين الأول والثاني من سلسلة تاريخ الاستعمار

جمعت بين الدقة والجمال.. متحف الكفيل يضم سجادة نادرة تعود لأكثر من ثمانية عقود

المزيد

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شكل الدماغ قد يتنبأ بخطر الخرف قبل سنوات

طريقة صينية بسيطة للوقاية من السكري

هل تساعد المانغو في الوقاية من السكري؟

المزيد

الآخبار التكنلوجية

رقم غامض ولا إنترنت.. متوجون بنوبل للطب لم يعلموا بفوزهم

"سيري" تحت المجهر.. تحقيق فرنسي جديد ضد شركة "آبل"

أميركيان وياباني يفوزون بجائزة نوبل للطب

تحول غير مسبوق.. إنستغرام تمنح مفاتيحها للمستخدمين

المزيد

مواضيع ذات صلة

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