Dr. V. Seshiah*, Dr. V.Balaji*,
Dr. Madhuri**, Dr. S. Aruna**
* Consultant Diabetologists
** Research Associates.
Diabetes mellitus is a " hormono-metabolic" disorder characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. Type 2 diabetes, the most prevalent form of the disease, is often asymptomatic in its early stages and can remain undiagnosed for many years.
The chronic hyperglycemia of diabetes is associated with long term damage, dysfunction and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels. Individuals with undiagnosed type 2 diabetes are at a significantly higher risk of coronary heart disease, stroke and peripheral vascular disease than the non diabetic population. They also have a greater likelihood of having dyslipidemia, hypertension and obesity. Because early detection and prompt treatment may reduce the burden of type 2 diabetes and its complications, screening for diabetes may be appropriate (1). The expert committee on the diagnosis and classification of diabetes (Table 1 and Table 2) has recommended eliminating the old categories of insulin dependant diabetes mellitus (IDDM) and non insulin dependant diabetes mellitus (NIDDM) because they are based on treatment which could vary considerably and did not indicate the underlying pathogenesis. Further, in discussing the types of diabetes, the use of Arabic (type 1 and type 2) rather than roman numerals (type I & type II) has been recommended to prevent confusion (eg. type II being read as type eleven). The committee has also introduced a new category of Impaired fasting glucose (IFG) where the fasting plasma glucose (FPG) is more than 110 mg/dl and less than 126mg/dl. It has also recommended a FPG of >126mg/dl as a diagnostic cut off point for estimating prevalence and incidence of diabetes (2). Here a clear distinction has to be made between diagnostic procedures for clinical purposes and for epidemiological studies. Measuring only fasting plasma glucose would not identify a large population of impaired glucose tolerance(IGT) who have a future risk of developing diabetes and macrovascular complications.
In the natural history of type 2 diabetes, progression from normal to impaired glucose tolerance is associated with the development of insulin resistance and accompanied by a compensatory rise in basal and post prandial insulin levels. With the worsening of insulin resistance the muscle glucose uptake gets impaired and post prandial plasma glucose rises. At this stage, the fasting plasma glucose is still normal as insulin available is adequate to suppress hepatic glucose output. Overall, insulin output continues to rise and peaks at a fasting glucose level of 140 mgs/dl (7.8 mmol). Beyond this level the beta cells become refractory to glucose which results in the deterioration of insulin secretion (3). As overt diabetes sets in, the insulin output falls and by the time the fasting plasma glucose value is 180 mgs/dl (10mmol/l) the insulin concentration is frankly subnormal. Now it can be safely hypothesized that the first abnormality that occurs is the rise in post prandial blood glucose. Fasting hyperglycemia occurs years later as insulin sensitivity worsens and insulin deficiency starts appearing.
As the primary aim in the management of diabetes is early detection and intervention early detection depends upon the testing for plasma glucose at the time of occurrence of an early abnormality in glucose metabolism. If screening for diabetes is done during fasting alone many persons who have glucose intolerance would not be identified and this would expose their system to abnormal glucose levels for many years and consequently a higher risk of vascular complications. It is not uncommon to find vascular complications at the time of diagnosis of diabetes. The recently published UKPDS results have shown that at diagnosis 50% had some form of tissue damage (4). Harris reported his findings from two cohorts of type 2 diabetic patients(5). The first group comprised 1166 subjects representing a stratified sample of type 2 diabetic patients from the Wisconsin study and the other group consisted of similar patients from western Australia. Over 21% of the Wisconsin patients and 10.5% of the Australian group already had retinopathy at the time of diagnosis. By regression analysis, the time at which vascular lesions were detectable was estimated to be as much as 4-7 years before the diagnosis of type 2 diabetes. Based on these data and data from the Whitehall study (7) probably type 2 diabetes begins 9 to 12 years before its clinical diagnosis (6 & 7).Testing for one hour or two hour post glucose blood levels identifies the patients at risk of developing diabetes in the future as the fasting plasma glucose is lower than the diagnostic criteria for diabetes at this stage. We analyzed 4000 GTT's of non diabetics who underwent master health check up at Apollo hospitals, Chennai. 1002 persons had either FBS>126 mgs/dl or 2 hour post glucose value between 140 mg to 199 mg/dl or 2 hour post glucose> 200 mgs/dl. When we categorized the 1002 persons on the basis of plasma glucose values, 71 had FBS >126 but 2 hour post glucose < 200, 602 had FBS <126 and 2 hour post glucose between 140 and 199, 219 had FBS>126 and 2 hour post glucose >200 and the remaining 110 had FBS <126 but 2 hour post glucose >200mgs/dl. (Table 3). The outcome of the study was that only 219 (22%) had both FBS and PPBS above the diagnostic cut off point for diabetes. Almost a similar conclusion was obtained in the NHANES survey, in that only 25% of those with a 2 hour plasma glucose value above 200 had a raised fasting plasma level (8). Franscisco J Gomez Perez et al have also reported that >80% of IGT could not be detected by following the expert committee recommendation (9). Kroll L.P. in his study found that estimation of fasting plasma glucose alone will underestimate the prevalence by upto 50%(10). From these studies it is obvious that the information obtained from FPG is not the same as that from a 2 hour post challenge plasma glucose. It would therefore be inappropriate to use the FPG criteria alone for screening diabetes in Asian population (11). Because by considering only the fasting plasma glucose for diagnosis of diabetes, we would have missed a large segment who had either IGT or diabetes.
The risk of progression to type 2 diabetes is high in persons with IGT. The rate of conversion varies from 2 to 16% per year (12).
Management of diabetes includes prevention of the disease and its complications. Every effort should be made to identify the earliest disturbance that occurs in glucose homeostasis. A number of studies have clearly shown that increase in post prandial plasma glucose is the earliest disturbance to occur. Hence all measures should be taken to identify the population belonging to this category and treat them. This is possible only by estimating 2 hour post glucose or OGTT in an index case as in the natural history of type 2 diabetes, the first abnormality that occurs is a rise in post prandial blood glucose.
Diagnosis of DM
|FPG <110||>/= 110 & <126||>/=110 & <126||>/= 126|
|2hr PG <140||>/= 140& <200||>/= 200|
|Symptoms of DM & RBG>/=200|
|* Values in mgs/dl|
On analysis of 4000 glucose tolerance tests at Apollo Hospital, 1002 had either
|2hr PPG||140-199 mg%|
|2hr PPG||>200 mg%||
Applying ADA criteria of fasting plasma glucose for diagnosis of diabetes mellitus
|FPG||2 hr PPG||No|
|<126||>200||110||Missed diagnosis of DM|