A 49-years-old obese male presented with generalised unwell being and pain in the knee joints Examination revealed BP of 160/100 m/Hg with no other abnormality detected. Investigation revealed fasting glucose of 211 mg% post prandial glucose 286 mg%, LOL cholesterol 166 mg%, triglyceride 302 mg%, HDL-32 mg%, uric Acid - 7.4mg%, urine for routine - glucose ++, trace of protein, EGG normal, X-ray chest- normal, T3, T 4, TSH - normal. He gave a family history of diabetes mellitus.

Diagnosis :Type II diabetes mellitus, hyperlipidaemia, hyperuricaemia
The incidence of diabetes mellitus is increasing at an alarming proportion and majority of them are Type II diabetes mellitus. Prompt diagnosis and treatment of diabetes mellitus can reduce the mortality and morbidity.

Unfortunately the individuals may have undetected diabetes for many years before they come into limelight following routine examination and many of them will already be having involvement of at least one organ.

Since this disease is taking an epidemic proportion in India, the primary care physician will have to bear much of the burden for diabetes management in the years ahead.

It is a well known fact that tight control of blood glucose reduces diabetes related complication. UKPDS study has shown that 1% reduction of HbA1C will cause:
21 % risk reduction in any diabetic related end point.
21 % reduction in diabetes related death.
14% risk reduction in MI.
37% risk reduction in microvascular complication.
So physicians should strive for meticulous glycaemic control.

The first step in that direction will be advice regarding life style modification which include dietary alterations, regular physical exercise, reduction of weight and reduced alcohol intake.
If with the aforementioned measures the target HbA1C level is not achieved then one should go for oral hypoglycaemic agent as monotherapy.

Which agent?
In the presence of obesity (BM I >23 kg/m2) metformin should be used first. This drug is contraindicated in renal and hepatic impairment.

Moreover some of the patients are intolerant to this drug (nausea, diarrhoea etc.) an alternative agent like sulphonylurea should be chosen. In patients with erratic life style or anticipated risk of hypoglycaemia or weight gain, a rapid acting secretagogue (repaglinide, nateglinide) should be used instead.

If the desired effect is not achieved with single drug, then combination therapy should be considered.
The following combination may be tried :
Metformin + Sulphonylurea (risk of hypoglycaemia should be considered)
Metformin + Nateglinide or repaglinide (they can control post prandial glucose well)
Metformin+Glitazone (Pioglitazone, rosiglitazone)
Suiphonylurea + Glitazone
One should remember that g/itazones take a while to exert their maximum effect (8-12 weeks).

Triple therapy: sulphonylurea + metformin + glitazone
Although not recommended in certain countries, in day to day practice this is a very helpful and effective combination to achieve adequate glycaemic control. Glitazones can cause fluid retention and oedema and therefore should be used with caution in patients with cardiac failure, Liver function should also be monitored.
Occasionally glucosidase inhibitors (Glucobay) may be added to control the post prandial surge. However its use is limited by its very embarrassing side effects of flatulance. If combination therary fails to achieve the goal within 6 months, drug therapy should be combined with insulin.

Which Insulin?
Initially once daily medium acting insulin (NPH Insulin) at bed time may be tried with a starting does of 10 units with the dose gradually titrated upwards.
However, it can cause nocturnal hypoglycaemia. Newer varieties o( long acting insulin -like glargine insulin is already available in some countries including India. The advantage is that it is a long acting basal insulin, thus the nocturnal hypoglycaemia is rarely a problem.
If single daily insulin is not sufficient enough to achieve adequate glycaemic control, then twice daily NPH insulin should be tried. Metformin can still be continued for synergistic effect. The other oral hypoglycaemics should be withdrawn. Another common practice in India is the combination of insulin with glitazone which is very effective.

In spite of these measures, HbA1 C is still out of range and the blood glucose fluctuates considerably, one should consider basal-bolus insulin (NPH insulin twice daily or glargine insulin once daily with rapidly acting regular insulin as bolus). Lispro insulin may also be used as a bolus with lesser risk of post prandial hypoglycaemia.
Sometimes the patients are unwilling to take multiple injections. In that event, premixed insulin in 1wice daily dosage is an alternative (Huminsulin 30/70 or Huminsulin 50/50).

While it is important to control the blood glucose, it is equally important to take care of hypertension and hyperlipidaemia they will adversely affect the outcome of the patients with diabetes mellitus particularly with regard to the macro vascular complications.
What is new?

The optimum treatement regime in Type II DM is combination of two insulin sensitizers (metformin + glitazones). This is because glitazones reduce other cardiac risk f.actors like hyperlipidaemias and they can even rejuvinate pancreatic beta cell function. Sulphonylurea may be added to the regime if the maximum dose of the initial combination fails.

Key points:
In India, primary care physicians have to share the burden of treating diabetes mellitus.
Metformin is the drug of choice in obese diabetics.
Judicious use of combination therapy will help control the blood glucose.
If combination therapy fails single dose long or medium acting insulin may be added.
Twice daily insulin can be effectively combined with metformin.
Combination of lispro insulin )bolus) and glargine insulin (basal) may be used in difficult cases.n (Reprint)
Source: “Experience with Evidence in Clinical Practice,” Dr. Subrata Maitra