Diabetes Mellitus – A Clinical Biochemist’s View
Diabetes Mellitus (DM) a household entity in today’s world, is one of the most challenging health problem of the 21st century.It has catapulted itself from a rare disease at the beginning of the century to the 4th commonest cause of mortality.The prevalence of diabetes is increasing worldwide.
The need of the hour is that the authorities as well as the public should awaken from their slumber and take a view of the delicate situation we are in right now, and prevent further progress on this road to diabetes.
To evaluate the risk factors it is essential that the patient undergo a careful history and detailed medical examination along with certain laboratory tests. Such tests include measurement of blood glucose, serum lipids- total cholesterol, HDL cholesterol, LDL cholesterol, Triglycerides, etc. and very important, but often overlooked test is for (micro and macro) albumin in urine. The importance of this test of urine cannot be overemphasized in today’s world in a diabetic care clinic setting.
Diabetes mellitus is a Hormono-metabolic disorder characterized by elevated circulating blood glucose levels resulting from defects in insulin secretion, action or both. Diabetes Mellitus has been classified as:
1. Type 1 diabetes (formerly known as insulin dependent diabetes mellitus), is a disease characterized by a total failure to produce insulin.
2. Type 2 diabetes (formerly called non-insulin dependent diabetes mellitus) usually arises because of insulin resistance combined with relative insulin deficiency. It typically occurs in middle age, overweight and sedentary persons, with a family history of DM.
3.Other specific types
4. Gestational Diabetes Mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. It generally manifests around 24-28 weeks of pregnancy.
Type 2 diabetes is the commonest form of diabetes constituting 90% of the diabetic population in any country.
For labeling a person as having DM, the criteria used at present, are according to the guidelines issued by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. A person is diagnosed as having DM, if he fulfils any one of the following conditions:
1) Symptoms of DM plus a casual plasma glucose concentration of >200 mg/dl.(Casual is defined as any time of the day without regard to time since last meal. The classic symptoms of DM include repeated urination, excessive thirst and unexplained weight loss.)
2) Fasting plasma glucose >126mg/dl.(Fasting is defined as no caloric intake for at least 8 hours).
3) 2 hour plasma glucose >200 mg/dl during an oral glucose tolerance test (OGTT-This test employs a sample in the fasting state followed by a glucose load of 75 grams dissolved in 250 ml of water, to be taken by mouth, and the next sample be taken 2 hours after consuming this).
If abnormal results are obtained in any of these tests they should be confirmed by repeating on another day and only then the diagnosis of DM should be served to the individual.
The terms “Impaired Fasting Glucose” (IFG) and “Impaired Glucose Tolerance” (IGT) refer to a metabolic state intermediate between normal glucose metabolism or homeostasis and diabetes, also referred to as pre-diabetes.The persons with IFG or IGT are those whose glucose levels do not meet the criteria for DM , but are too high to be considered as altogether normal. IGT is by itself not a benign condition. It’s prevalence varies from 2-16.4 % in different populations. The rate of conversion of IGT to DM is from 2.5 – 5 % per year. The risk of conversion is higher in patients with high plasma glucose levels at the time of diagnosis of IGT, increasing age, obesity- more so central obesity, recurrent infection, etc. Risk of coronary artery disease is higher in IGT patients. Diet modification and exercise are the mainstay in the management of subjects with IGT. Several different studies have demonstrated that the progression of IGT to DM is delayed. This classification divides the population into three categories when we use fasting plasma glucose (FPG) levels for diagnosis:
- FPG < 110 mg/dl = Normal fasting glucose;
- FPG from 110-125 mg/dl = IFG
- FPG 126 mg/dl or above = provisional diagnosis of DM, (diagnosis to be confirmed)
The corresponding categories when the OGTT is used are;
- 2-hour postload glucose(PG) upto139 mg/dl = normal glucose tolerance
- 2-hour PG 140-199 mg/dl =IGT
- 2-hour PG 200mg/dl or above = provisional diagnosis of DM (diagnosis to be confirmed).
With diet and exercise therapy, even medicines may be used.
A question which must have cropped up in the mind of many readers by now is I am healthy, should I get myself investigated for DM? Well friends, here is the answer to your query.
You need to get tested if you are 45 years of age or above, particularly if your Body mass index( BMI )is 25 or above. Also, if your results are normal now, you can be at ease for the next 3 years as that is the time you will need to repeat it, every 3 years till it continues to be normal.
Ideal body weight is: [(Height in cm’s) – 100] x 0.9 cm’s
(Height in meters) squared
If you are not yet 45 years of age , the recommendation for you is that you should go in for testing if you are overweight i.e. your BMI is 25 or more, and you have an additional risk factor or more – like a first degree relative with DM, are habitually physically inactive, are from a high risk ethnic group, have delivered a baby over 9 pounds, have high blood pressure, have HDL cholesterol of 35mg/dl or less , have triglyceride level of 250mg/dl or above, have polycystic ovary disease, or on a previous testing had IFG or IGT, or have a history of vascular disease.
Although the OGTT and FPG are both suitable tests, in clinical settings, FPG is recommended more because it is easier to perform, faster test, more convenient and acceptable to patients, more reproducible and less expensive. This approach grossly under diagnoses this global problem as there are a lot of people who will have a normal FPG , but will have an elevated 2-hour PG ,which may be in the impaired zone or in the overt diabetic range. It has now been hypothesized that the first abnormality that occurs is the rise in post-prandial (after meals) blood glucose. Fasting levels rise to abnormal values much later, even many years later, as insulin sensitivity worsens and insulin deficiency starts appearing. Hence the more meticulous physician will advise you to go in for both a fasting and a post glucose load blood glucose estimation to be on the safer side. This is actually very much in the interest of the patient, although it may appear cumbersome to many individuals, because the vascular damage will occur if high circulating glucose levels persist for a longer time. More so, more than half the patients would already be having complications as a result of vascular damage at the time they are diagnosed as having DM using the FPG approach. Actually, the primary aim in the management of diabetes is early detection and intervention. Early detection can be done by testing for plasma glucose at the time of the occurrence of an early abnormality in glucose metabolism. If we continue to screen the population with only FPG levels, many persons who have glucose intolerance would not be identified and this would expose their system to abnormally high levels of glucose for many years, and result in tissue damage. Testing blood glucose after a glucose load will help to identify patients at risk of developing diabetes in the future, as we shall be able to pick up those with impaired glucose tolerance as well, who are likely to get converted to overt DM later on. There are few persons in the the early stage of the disorder, who will show an abnormality in both test results— fasting and post-load glucose estimation, hence it is best to have both tested if one has to be doubly sure and one can afford it in terms of time and money.
At this juncture, it seems appropriate to talk about the much- practiced test of urinary sugar. This test is advocated by general practitioners to get an overview of the glucose metabolism in an individual. There is as such nothing wrong with this test, if used judiciously. High degree of dependency on this test is often misleading as there are numerous persons with no sugar in their urine, but very high blood sugar levels. This test may at best be used in conjunction with blood glucose estimation, to avoid missing an important diagnosis.
To monitor diabetes is a very meticulous affair, more so, with rising number of diabetics and the associated rise in complications as well. Most often, a newly detected diabetic is not one whose disease is of recent origin, it is just that it has been detected recently. There is an analysis termed the glycosylated haemoglobin, that tells about the glycaemic(glucose metabolism) status of the individual in the past three months or so. Normally it’s levels should be < 7 , but if the blood glucose has remained elevated in the past few months( approx. 8-12 weeks), then its levels are bound to be higher in the range of 12-25. Estimation of lipid profile is very essential in these patients. After starting medication, it is advised that the patient gets a follow up after 3 weeks with a fasting and post- glucose load blood glucose estimation. A glucometer for repeated testing at home is highly being recommended these days. A less popular test is that for glycosylated albumin, which detects the glucose status in the past few days as against few months previous status depicted by glycosylated haemoglobin. Limitation is that this test is not freely available for routine use.
Since diabetes affects multiple organs, so the monitoring is in no way complete by just monitoring blood glucose, it being imperative to monitor the cardiac, renal (kidney) and ophthalmic (eye) status as well of every diabetic patient.
Since there is a higher chance of concomitant coronary artery disease in diabetic subjects, it is very important that the cardiac status of every diabetic individual be assessed properly with an ECG (Electrocardiogram), an echocardiography, and lipid profile analysis. The peripheral pulses must be examined for any evidence of peripheral vascular disease.
Since peripheral nerves get affected in persons whose diabetes is poorly controlled after an year or so, a peripheral nerve conduction test should be done to document this problem. In general, it is advisable to supplement vitamins of the B complex group to all diabetics, but definitely on prescription.
It is very much important that in every known diabetic, an effort is made to look for microalbuminuria (detection of trace amount of albumin in urine) at least annually. The best method for this is to collect a 24 hour urine sample and go for its protein content estimation. Also important for determining the renal status are estimations of urea and creatinine in the blood. In certain cases, creatinine clearance may be indicated, but that should be left to your clinician to decide, which investigation is needed and when. Once the renal status is affected, it may be advisable to change to medicines that do not cause a further impairment of renal function. Also, your physician may as well put it in block letters on your treatment card that other classes of medicines which cause renal damage should definitely be avoided for treatment of other problems.
Along with the general health check up, an annual eye check-up is very vital to rule out any retinopathy.
It is very important that diabetes be ruled out in patients with recurrent abortions. Once the patient conceives, there is need for insulin and dietary control along with periodic monitoring of blood glucose levels for a successful outcome of pregnancy.
Management of diabetes is not just the use of drugs and insulin , it is in fact the management of complications and the associated disorders that add useful years of life of the patient.
There is at present need for well-organised diabetes detection camps, and also education camps for bringing about a social revolution by bringing about awareness in the masses. Since diabetes is a leading cause of mortality among the general population, and the rising trend of prevalence has placed the disease as a major public health problem, screening is useful for many reasons. First, as there is a sub-clinical stage of this disorder when there is no clinical evidence of the problem, a lot of persons who would otherwise remain undetected for say even up to 7-8 years would be diagnosed. Secondly, we can pick up persons who are likely to land into diabetes later on in life, and help them delay the onset of diabetes. Thirdly, early detection will help in better control by early commencement of treatment, which will help in preventing, or delaying the onset of complications. Diabetes detection camps can be held in general population, or in persons who are at higher risk for developing the disorder. They can yield anything from 5-40 %, which will depend on what subjects are screened, and what is the screening procedure used. Diabetes detection camps also give us an opportunity to educate the public regarding this global problem.
Common Errors in the Management of Diabetes
Errors in investigation
- Post glucose blood sugar is not done in known diabetics
- Post glucose blood sugar estimation without anti-diabetic agent
- Fasting urine sugar examination from overnight sample
- Fasting blood sugar >300-400 mg/dl, and ketone bodies not tested
Errors in Evaluation
- B.P. and weight not recorded
- Retinopathy, Neuropathy and Coronary artery disease status not ascertained
- Chest x-ray (for TB), abdominal x-ray (for renal stones), and ultrasound (for gall stones) not done
In appropriate situations
Errors in the treatment
- Dietary advice(chart) not given.
- Physical activity not advised.
- Treating diabetes with urine sugar report.
- Patients not made aware of symptoms of Hypoglycemia, and measures for it’s correction.
- Not advising correction of refractive error during high blood sugar.
- Pregnancy diabetes treated with oral anti-diabetic agents.
- Techniques and site for injection not properly demonstrated.
- Ideal insulin syringe for the type of insulin not advised.
- Unnecessary change of prescription with change of physician resulting in early failure of oral anti-diabetic therapy.
- Wrong drug schedule
Most of these Errors have been minimized following the setting up of Diabetic Care Clinics and the shift of the masses towards qualified Physicians and even super specialists.
Dr. Seema Garg
M.D. (Biochemistry)
Medical Officer, Civil Hospital, Hoshiapur.
M.D. (Biochemistry) Medical Officer, Civil Hospital, Hoshiapur.
