Beneficial effects of triple drug combination of pioglitazone with glibenclamide and metformin in type 2 diabetes mellitus patients on insulin therapy.

BACKGROUND: The thiazolidinediones are a class of antidiabetes medication that enhance the actions of insulin in muscle, liver, and adipose tissue. Data have been lacking on their use in combination with both sulfonylurea and metformin among patients of type 2 diabetes who are on insulin therapy secondary to failure of routine oral hypoglycemic drugs in controlling their diabetes. OBJECTIVE: To determine the effects of pioglitazone in combination with sulphonylurea and metformin on diabetes control in patients being treated with insulin due to secondary failure of oral hypoglycemic agents. PATIENTS: One hundred and twenty-four consecutive type 2 diabetes patients (mean age, 57.13 years) attending four centres in Mumbai, who were being treated with insulin were selected. They were switched on to triple drug combination of glibenclamide 5 mg, metformin 500 mg and pioglitazone 15 mg along with insulin. Study participants were required to have type 2 diabetes mellitus for atleast 5 years. Patients were excluded if they had any of the following: serum creatinine concentration greater than 1.5 mg/dl, alanine aminotransferase (ALT) level more than two times the upper limit of normal, symptomatic angina, cardiac insufficiency or history of myocardial infarction. RESULTS: Pioglitazone 15 mg with glibenclamide 5 mg and metformin 500 mg, significantly decreased hemoglobin HbA1c level from 11.5% to 7.32% (P < 0.001), average fasting blood glucose from 194.8 mg/ dl to 124.06 mg/dl (p < 0.01), average post-prandial blood glucose from 256.24 to 162.32 mg/dl (p < 0.01). At 6 months, 43.35% of patients did not need to be continued on insulin. The total insulin requirement in 124 patients reduced by 71.81%. There were no significant side effects, liver enzymes were within acceptable levels, average weight gain was 2.23 kg, significant hypoglycemia was observed in 28 patients with two requiring hospitalisation, these patients were those who did not stick to follow-up schedules. CONCLUSIONS: With proper patient selection, pioglitazone with glibenclamide and metformin can be safely used in patients receiving insulin with good results.

Evaluation of a short course on diabetology for practising doctors.

A short course on Diabetology, attended by 83 doctors was evaluated. The doctors were divided into three groups. (Group I--basic qualification MBBS, Group II--MD in medicine or allied subject, Group III--Diploma in Diabetes Mellitus). The mean age group of all three groups were comparable. Pre-course evaluation of their knowledge of diabetes showed the best performance in Group III and poorest in Group I. Post-course evaluation showed significant improvement only in Group I and II. Maximal improvement in performance was seen in Group II. Mean time since passing the last professional examination was 14.8, 12.6 and 1.0 year respectively. The performance was not linked to time since passing the last examination. 14.5% of doctors were from a rural or semiurban setting. The precourse performance of rural doctors in the MD group was significantly poorer, but their post course performance was as good as the others. All doctors from rural or semiurban areas improved their performance postcourse, compared to 84% in the urban group. 74% of doctors had not attended any post graduate course after their basic degree. Their performance did not differ significantly from those who had attended such courses. 44.6% were Consultants, 26.6% were general practitioners, 12.0% were attached to institutions, 10.8% were in government service or armed forces and 6% were attached to teaching hospitals. The performance of the doctors was not linked to the type of practice. The doctors attending the course felt that the audiovisual presentation needed improvement.

Bilateral optic nerve infarction following acute systemic hypotension and anemia--a case report.

Presented here are case reports of two patients who became completely blind in both eyes following acute systemic hypotension - in one following bouts of vomiting and in the other after repeated gastrointestinal bleeding. Both patients had severe degree of anemia. There were no other risk factors for vascular disease such as arteriosclerosis or vasculitis.

Carotid sinus syndrome associated with carcinoma of the pyriform fossa.

A patient who developed syncope due to carotid sinus syndrome is described. The patient was suffering from carcinoma of the pyriform fossa for the past one year and received radiotherapy in the region of the neck for the same. Demand pacing was ineffective in alleviating syncopal episodes. The patient responded to oral administration of an anticholinergic (belladonna) and a sympathomimectic agent (orciprenaline).

Biguanide-induced lactic acidosis.

Phenformin-induced lactic acidosis has been thought to be rare in India due to a high carbohydrate intake, use of suboptimal doses of phenformin and a lesser prevalence of alcoholism, as compared to Western countries. We studied the blood lactate levels of 31 non-insulin dependent diabetics (Group A) before and after treatment with phenformin, 75 mg/day for 4 weeks. Blood lactate rose significantly after treatment (mean +/- SEM 16.6 +/- 1.2 mg/dl to 30.7 +/- 2.2; p less than 0.01). Seven patients from this group had blood lactic acid level greater than 72 mg/dl. Six of these patients were restudied off treatment and after 4 weeks of phenformin therapy. The arterial blood pH, pCO2, pO2 and bicarbonate remained unchanged on treatment although a significant rise in blood lactic acid was reconfirmed in these 6 patients. Another group of 12 patients on phenformin for more than six months had significantly lower blood lactate levels as compared to group A (mean +/- SEM 20.2 +/- 1.8 mg/dl vs 30.7 +/- 2.2 mg/dl; p less than 0.01) indicating the possibility of a process of adaptation on prolonged treatment. This possibility was confirmed by a serial follow-up study of 11 patients for a 6 month period on phenformin therapy. A case of biguanide-induced lactic acidosis diagnosed and treated by us is described.