Diabetes is a group of diseases that cause abnormalities in the function and structure of tissues and organs due to high blood glucose levels. The disease state should be such that tissue and organ damage occurs before making a diagnosis, which would be too late. It is reasonable to use the characteristic lesions triggered by blood glucose for diagnosis. However, blood glucose is a continuous variable, and it is obviously unreasonable to use a little level of blood glucose as the diagnostic cutting point of the disease. Therefore the diagnostic criteria for diabetes mellitus blood glucose is established as a relative level, i.e. the point above which the glycemic state triggers the onset of statistically significant elevation of hyperglycemic characteristic lesions. In a population, the cut-off point of blood glucose level may vary to some extent in the population depending on factors such as population, age, gender and living environment. The cut point between normal and abnormally high glycemic states is artificially determined, but is critical for clinical management. The main basis for the delineation of the cut point for diabetes diagnosis is the effect of blood glucose on retinopathy. It is also based on the need of diabetes and its complications prevention and control, and the consideration of health economics and the ability of the population to tolerate the concept of the disease. The diagnostic criteria for hyperglycemia in diabetes are based on the high blood glucose values that cause damage to the microvasculature and not on the blood glucose values at which diabetes develops symptoms.
Incomplete blood glucose testing leads to too high a rate of underdiagnosis of diabetes. If the diagnostic criteria for diabetes were not based on the “three more and one less” symptoms, how many people with diabetes would be hidden among the normal population because they have no symptoms? This means that the underdiagnosis rate of diabetes is as high as 70%. This indicates that the early stage of diabetes is not detected due to the lack of obvious symptoms and the blood glucose has already reached the stage of hyperglycemia which is harmful to the organism. This is the case even in developed countries where the rate of underdiagnosis of diabetes is about 50% in diabetes surveys.
The gap between the symptoms of diabetes and the diagnostic criteria is the blood glucose level. The patient’s “three more and one less” are late symptoms, and the distance between the blood glucose value of diabetic symptoms and the target value of blood glucose control is too large, so the blood glucose must be monitored to know its level. In clinical treatment, many patients are treated by their symptoms only, and lose the time of long-term hyperglycemia but not treated, which is extremely wrong. Many diabetic patients experience the process of not monitoring blood glucose in the early stage and letting high blood glucose persist for a long time only by self-perception; some patients, although they have good health care conditions, just do not know the meaning of blood glucose control and do not keep their blood glucose in a good range for a long time.
Monitoring indicators of blood sugar and its significance.
Since there are no obvious symptoms of mild to moderate hyperglycemia, blood glucose monitoring is the only way to know the level of blood glucose. There are two major categories of blood glucose monitoring indicators, one representing long-term blood glucose and the other being point glucose indicators. The former has glycosylated hemoglobin (HbA1c) and glycosylated serum protein, and the latter includes multi-point pre-meal, post-meal and bedtime blood glucose.
It refers to the protein glycation product formed by blood glucose and hemoglobin in red blood cells. In adult life, hemoglobin is mainly HbA, which accounts for 97% of the total, and the part that is glycated is called HbA1, where HbA1c represents the major glycated HbA1 fraction.
Since the life span of red blood cells is 120 days, the formation of glycated hemoglobin represents the average life span of red blood cells in the blood. If blood glucose levels do not fluctuate much, the average blood glucose and HbA1c levels over about 3 months correlate well and probably represent the average blood glucose level over the 2 to 3 months prior to the measurement. However, the blood glucose of diabetic patients is unstable, and a study found that 50% of the HbA1c level is mainly the result of glycation of the average blood glucose in the month before the measurement, indicating that the level of the average blood glucose in the recent month occupies an important influence in the formation of this glycated hemoglobin, which is more helpful for changing the therapeutic drugs during clinical treatment. In the other 50%, about 40% of the HbA1c was more related to the average blood glucose in 2 to 3 months before the measurement, and only 10% represented the average blood glucose level in 3 to 4 months. 1441 cases of type 1 diabetes in the DCCT study provided a large amount of data related to multi-point blood glucose, average blood glucose and HbA1c, and the correlation between HbA1c and average blood glucose was good, and the relationship was deduced through statistical calculation The formula, using the level of HbA1c to calculate the recent average blood glucose level. The following table is specially listed for clinicians in order to use the easy HbA1c measurement results to deduce the recent average blood glucose.
It is easy to remember that if HbA1c=6% corresponds to an average blood glucose of about 7.5mmol/L, then for every 1% increase in HbA1c, the average blood glucose increases by about 2mmol/L.
At present, HbA1c is widely used for long-term blood glucose monitoring of diabetic patients. Whether it is to study the effect of blood glucose on chronic complications or to judge the effect of various hypoglycemic drugs, HbA1c is the “gold standard” currently in use. It is a very good choice to measure twice a year for those with stable conditions and four times a year for those with unstable conditions, and fasting and postprandial glucose can be used instead in areas without conditions.
Glycated serum protein (GSP).
As blood glucose fluctuates within the normal range, glucose also binds to a small amount of protein in the serum to form glycated serum proteins. The average lifespan of serum proteins is about 4 weeks with a half-life of 2 weeks, so glycated serum proteins represent the average level of blood glucose over a 2-week period. It represents a more recent average blood glucose level compared to HbA1c and is also more helpful for treatment, and is not widely available in the clinic because of the difficulty of measuring it.
Point glucose.
Point glucose is not only a criterion for determining the diagnosis of diabetes, but also a good indicator to guide the medication in diabetes treatment. Since both fasting and postprandial hyperglycemia are clinical types of hyperglycemia, they represent the sensitivity of different organs to insulin and the degree of hyperglycemia in different diabetes respectively, and therefore both are important in clinical use.
Fasting glucose mainly represents the amount of glycogen isogenesis and glycogen output of the liver and the ability of insulin to inhibit glycogen output of the liver. Since it is a non-meal state, it can respond to endogenous islet function to a great extent, in addition to insulin resistance of the liver. Most of the early diabetics and those with impaired glucose regulation are predominantly hyperglycemic after a meal or sugar load, with relatively low fasting glucose. Only about nearly a quarter of the population exhibits increased fasting glucose alone. Patients in the middle and late stages of diabetes have a progressive decline in endogenous islet function. Although the absolute value of postprandial blood glucose is high with the increase of fasting blood glucose. But the increased value is relatively fixed. The focus of fasting and postprandial blood glucose treatment needs to be individualized.
Point glucose can be measured by self-monitoring using a glucose meter, which correlates well with venous plasma glucose values, especially in the moderate to high glucose regions, due to the constant updating of the meter. Very high or very low areas are less well correlated.
Spot glucose is mainly used to adjust the dose of therapeutic medication, especially in patients on insulin; it is also a means to detect hypoglycemia. In addition, it can be compared with HbA1c by multi-point long-term spot glucose monitoring. In general, for patients with stable blood sugar, point blood sugar can be measured every 1 to 2 weeks for one day, and for those with unstable blood sugar, it can be measured according to the need of the disease.
Relationship with point glucose.
When the importance of fasting and postprandial glucose in diabetic patients was controversial several years ago, it was mainly found that postprandial or postload hyperglycemia in a portion of the hyperglycemic population was associated with the risk of future cardiovascular events. Fasting glucose was not associated with the risk of future cardiovascular events in these populations, so it was concluded that control of postprandial hyperglycemia is one of the important aspects in the prevention and treatment of macrovascular disease in diabetes. This conclusion is true in people with early diabetes or impaired glucose regulation, but it cannot be said that treatment of postprandial glucose is the most important aspect in all diabetic populations, hence the argument of who is most important, fasting glucose or postprandial glucose. The study from French scholar Monnier answered the relationship between HbA1c and point blood glucose. In 290 diabetic patients, the relationship between multi-point blood glucose test and HbA1c was calculated that when HbA1c<7.3%, the contribution of the increased part of postprandial blood glucose to HbA1c reached 70%, and the contribution of fasting and postprandial blood glucose accounted for half each for those with 7.3%-8.4%, and when When HbA1c>8.4% or more, the contribution of fasting blood glucose not only exceeded the value-added of postprandial blood glucose, but also rose continuously with the increase of HbA1c level. Since the effect of fasting and postprandial glucose was different in patients with different glycated hemoglobin levels, this study addressed the difference in the contribution of fasting and postprandial glucose value-added to different HbA1c. As patients progressed from moderate hyperglycemia to severe hyperglycemia, the respective contributions of fasting and postprandial glucose changed gradually, with the contribution of postprandial glucose drift being greater below moderate hyperglycemia and the effect of fasting glucose on HbA1c gradually increasing above moderate hyperglycemia, and fasting glucose showing a more important role as diabetes worsened. This study also points out to clinicians that they should individualize the order of point glucose treatment for patients according to different levels of HbA1c and focus on different periods.
Physiological variables.
Although HbA1c is the gold standard for long-term glucose monitoring in diabetic patients, and blood glucose levels are undoubtedly an important determinant of HbA1c, and studies in diabetic populations have shown that HbA1c is closely related to prior mean glucose, physiological variation still exists across individuals. The mean blood glucose and HbA1c levels and and predicted HbA1c (calculated values) measured quarterly in 1441 subjects in the DCCT database were analyzed, assuming that if the mean blood glucose correlates well with the predicted HbA1c, then the actual measured HbA1c levels should differ very little from the predicted HbA1c. The actual measured HbA1c-predicted HbA1c for each patient was taken to derive the difference in HbA1c, referred to as the hemoglobin index (HGI). Dividing the HGI into high, medium and low groups, after 7 years of follow-up, the risk of retinopathy and nephropathy was 3 and 6 times higher in the high HGI group than in the low HGI group after adjusting for mean glucose, age, treatment grouping, stratification and duration of diabetes mellitus (p<0.001). Suggesting that physiological variation among individuals with HbA1c is also at least a predictor of diabetic complications, there are still unknown factors at play in addition to the effect of HbA1c produced by mean glucose.
In conclusion, the glycemic diagnostic criteria for diabetes mellitus are based on glycemic values that appear meaningful for microvascular disease as a determination of disease status. HbA1c is currently a good indicator of long-term glycemic control, but attention should be paid to the physiological variability among individuals. 2005 IDF guidelines for the treatment of diabetes state that the standard value for glycemic control in patients with diabetes is HbA1c <6.5%. In areas where there is no condition to measure HbA1c, point glucose can be used instead. Point glucose equivalent to HbA1c<6.5% is fasting glucose <6.0mmol/L and 1 to 2 hours after meal glucose <8.0mmol/L.
Blood glucose meter.
The current blood glucose meter for clinical use is easy to operate and the results are accurate. When choosing a blood glucose meter, its characteristics and the convenience of patient application should be considered (such as consideration of vision and non-right-handedness). The instruments may differ in size, the amount of blood needed, the speed of measurement, the storage of results or not, and the price of the instruments and test strips.
Some blood glucose meters allow blood to be taken from places other than the fingertips, such as the upper arm, forearm, and thigh. However, it is generally accepted that blood taken from the arm does not reflect hypoglycemia and hyperglycemia as quickly as at the fingertip. Or, the fingertip can show blood glucose changes more quickly than other areas. The blood glucose meter may have other features such as automatic timing, error codes, signals, and reading the test strip lot number for calibration. For patients with visual impairment, some blood glucose meters can give voice prompts or have larger displays.
Importance of accuracy.
The reliability of a patient’s SMBG measurements presents a challenge in dealing with diabetes. When reporting blood glucose levels, patients may adjust high or low readings to narrow the gap between ideal values. This makes it important to educate patients that monitoring their blood glucose should be specifically emphasized to maintain a patient’s daily blood glucose close to normal.
Making patients aware that the glucose meter has a memory function can help improve the reliability of SMBG measurements. In a study of intensive therapy for type 1 diabetes, it was found that the memory function of the glucose meter with computer-assisted analysis improved glycemic control more than a form of glucose meter to diary. Intensive therapy included monthly blood glucose measurements, interviews with the nurse responsible for monitoring blood glucose control and compliance with treatment, and adjustments to the treatment plan when needed. All patients had been on an insulin pump or 4 daily insulin injections for 1 year prior to starting the memory-based glucose meter. Although the frequency of measurement increased from 4.59 to 5.25 times per day, the difference was not significant. However, the change in HbA1c values correlated with the frequency of glucose monitoring. This study confirms that blood glucose readings and systematic interpretation can help patients maintain self-care behaviors and strive to meet standards. Patients should be told to bring a glucose meter to their appointment visits so that they can perform self-testing on the spot to improve patient self-measurement techniques and accuracy of measurement, and frequent education on testing techniques can ensure accuracy of measurement.
Monitoring.
Values represent the combined fasting and postprandial glucose levels over the past 3 months. the ADA recommends that HbA1c be measured preferably twice a year for patients with diabetes who meet the standard, and four times a year for those who do not meet the standard or who change their treatment regimen. Instruments that provide rapid HbA1c results can help improve glycemic control. A randomized prospective controlled study compared the differences between laboratory methods of measurement and methods that provide results immediately when treated with insulin. At baseline, HbA1c was 8.67% and 8.49%, with comparable insulin dose and number of daily injections. at 6 and 12 months, HbA1c improved significantly in the immediate results group (-0.57% and -0.40%; p<0.01), while it was not significant in the control group (-0.11% and -0.19%). Although no behavior-specific changes were found, it was found that the frequency of insulin injections increased in the HbA1c immediate outcome group (p<0.001), suggesting that the measurement resulted in a change in the patients' injection regimen. This result supports the hypothesis that rapid use of the test results in clinical treatment would be beneficial for achieving ideal glycemic control.
Although HbAlc is the standard measure of long-term glycemic control, it is not suitable for diabetic patients with shortened erythrocyte lifespan such as hemoglobinopathies and blood loss. In such cases, measurement of mean glucose level or fructosamine level is a better indicator of glycemic control than measurement of glycosylated hemoglobin. There is evidence that the response to elevated blood glucose HbAlc varies between individuals and that 62% of this population variation is a genetic effect. Recent data suggest that biological variation in HbA1c values is a predictive risk factor for retinopathy and nephropathy in patients with type 1 diabetes. However, the source of the variation is unclear.