Do geriatrics require dose titration for antidiabetic agents?

OBJECTIVE: To evaluate the antidiabetic drug dosage differences between geriatric and nongeriatric diabetics with reference to duration of disease and creatinine clearance (Crcl). MATERIALS AND METHODS: Prospective study conducted for 6 months in a tertiary care hospital. Patients with type 2 diabetes mellitus were grouped into geriatric (age ≥60 years) and nongeriatric (age <60 years). Patients' demographic data, duration of diabetes, medication, and serum creatinine were recorded. Crcl was calculated using Cockcroft-Gault formula. Doses of sulfonylureas (SU) were converted into equivalent doses, taking glibenclamide as standard. Univariate analysis was done for comparison of drug doses between groups. RESULT: A total of 320 geriatric and 157 nongeriatric diabetics completed the study. The duration of diabetes and Crcl adjusted dose reduction of glibenclamide (mean dose: Geriatrics 7.2±0.4 mg, nongeriatrics 9.6±0.7 mg; P=0.01) and gliclazide (mean dose: Geriatrics 85.5±11.5 mg, nongeriatrics 115.3±32.7 mg; P=0.42) was 25%, glimepiride (mean dose: Geriatrics 1.62±0.13 mg, nongeriatrics 2.1±0.18 mg; P=0.06) was 22%. Glipizide did not require dose reduction. Mean converted equivalent dose of sulfonylurea monotherapy was significantly lower in geriatrics than nongeriatrics (3.2±0.5 vs 6.4±1.02 mg; P=0.01) and showed 50% dose reduction. Mean dose of metformin was lower in geriatrics (901±32.2 mg vs 946.7±45.8 mg; P=0.45) and showed 5% reduction in dosage. There was no difference in the mean drug doses of thiazolidinediones and insulin between the groups. CONCLUSION: A substantial dose reduction of glibenclamide (25%), gliclazide (25%), glimepiride (22%), and metformin (5%) in geriatrics compared to nongeriatrics was observed. Smaller dosage formulations like 0.75 mg glibenclamide, 0.5 mg glimepiride, 20 mg gliclazide, and 250 mg metformin may be of value in geriatric diabetic practice.

Co-administration of haloperidol and drugs affecting the angiotensin pathway: effect on the extrapyramidal system.

The present study investigates the extrapyramidal effects of co-administration of enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin receptor blocker) with haloperidol in mice. Enalapril/losartan (as a suspension in 1% gum acacia) was administered by oral gavage and haloperidol was administered as an intraperitoneal injection to all the animals for seven days. Catalepsy was measured 30 min after the administration of haloperidol (1 mg/kg i.p.) on days 1 and 7. Observations on day 1 constituted the acute study (single dose administration) and observations on day 7, constituted the chronic study (repeated dose administration). Both acute and chronic administration of enalapril/losartan produced an increase in the duration of haloperidol induced catalepsy at the highest dose (20 mg/kg). Enalapril produced a more pronounced increase in the duration of catalepsy as compared to losartan on both acute and chronic administration. Results of our study suggest that co-administration of anti-psychotics and drugs affecting the angiotensin system can lead to an increase in motor side effects and therefore should be used with caution in patients with these co-morbid conditions.

Prevalence of metabolic syndrome (METS) using IDF 2005 guidelines in a semi urban south Indian (Boloor Diabetes Study) population of Mangalore.

OBJECTIVE: To identify metabolic syndrome (MetS) prevalence using International Diabetes Federation (IDF) 2005 guidelines in a semi urban south Indian (Boloor Diabetes Study) population of Mangalore. METHODS: Population of randomly selected adults > or =20 years living in Boloor locality who were available for the house to house survey were assessed for the following: anthropometric variables; blood pressure; fasting blood glucose and lipid profile. Among 800 responders; 300 men, 500 women, 551 were examined (68.8%). Fasting plasma glucose as well fasting lipid profile could be done for 451 (147 men, 304 women) 81.85%; Data was analysed for prevalence of MetS and its individual components. Diagnosis of MetS was based on IDF 2005 criteria for Asian men and women. Intergroup comparisons were performed using student 't' test and Chi-square test. RESULTS: MetS was prevalent in 134 of 451 (29.7%); men 39 (26.5%) and women 95 (31.2%). Prevalence of individual components of MetS were as follows: increased waist circumference, (common component) present in all; elevated TG in 38.8%; low HDL-C in 59.7%; increased FPG in 57.4%; elevated SBP in 80.5% and DBP in 56.7%; body mass index (BMI) > or =25 kg/sq.m (obesity) in 58.9% Barring increased waist circumference which is the essential criteria for diagnosis of Mets, Systolic hypertension emerged as the most frequent component in the population followed by low HDL-C and elevated FPG. Elevated TG was less prevalent in this population. CONCLUSION: Prevalence of MetS in this semi urban population (Boloor) of Mangalore compares with MetS prevalence identified in cross sectional studies in India. Prevention and treatment of the predictive factors: dyslipidemias, hyperglycaemia, hypertension, together with enhanced physical activity may together reduce the prevalence of MetS.

Metabolic syndrome among inmates of a 'home for aged' using IDF 2005 criteria.

To identify the metabolic syndrome (MetS) among inmates of a 'home for aged' using IDF 2005 criteria. 100 subjects from inmates of a 'home for aged' studied for the identification of metabolic syndrome using International Diabetes Federation (IDF) 2005 criteria. Presence of waist circumference (WC) (Men > or =90 cm, Women > or =80 cm) plus any two of the following four factors; triglycerides (TG) >150 mg/dl (1.7 mmol/l), (II) HDL-Cholesterol (HDL-C) <40 mg/dl (1.0 mmol/l) for men, <50 mg/dl (1.3 mmol/l) for women, fasting plasma glucose (FPG) > or =100 mg/dl (6.1 mmol/l) and blood pressure (BP) > or = 130/85 mm of Hg. Indicated the MetS. MetS was present in 57.0%. WC was common component, TG was increased in 71.9%, low HDL-C present in 86.0%, raised FPG present in 66.7% and hypertension in 45.6%. MetS was more common in older women than in men (63.6% vs. 48.8%) and decreased HDL-C is core components of the MetS in this population. High calorie diet and sedentary life style may be contributing factors of MetS in this population. MetS is common in elderly subjects. It is age-related, and is more common in elderly women.

Serum bicarbonate: can it be a marker of metformin induced acidosis in geriatrics?

Metformin is an oral antidiabetic agent, widely used in the treatment of type 2 diabetes mellitus. The serious side effect of metformin therapy is lactic acidosis. Contraindications for metformin therapy include renal insufficiency. A cut off value of 60 ml/min in creatinine clearance is suggested. Hundred type 2 diabetics receiving metformin as monotherapy or in combination with insulin/other oral antidiabetic agents, were enrolled in the study. Patients were on metformin for atleast one month prior to being enrolled. Patients' demographic data were taken. Baseline serum creatinine and bicarbonate were estimated. Creatinine clearance (Clcr ml/ min) was calculated. Patients were grouped into group 1-4 depending upon the doses of metformin they received. Patients were again grouped based on their Clcr as groupA (Clcr < 60 ml/min), group B (Clcr > 60.01 ml/min). Data was analysed using student's t test. Out of 100 patients 52 were males, 48 females. Mean age and SD of males and females were 69.92 +/- 6.95 and 66.85 +/- 5.72 respectively. Comparison of mean bicarbonate level in different doses of metformin did not show any statistical significance. But comparison of bicarbonate levels based on Clcr were highly statistically significant (p = 0.0084). In three patients whose bicarbonate level was very low (15, 16.4 and 19.2 mmol/L), doses of metformin was reduced and after one month their bicarbonate levels returned to normal (27.4, 25.6 and 26.2 mmol/L). Hence serum bicarbonate can be a marker to assess metformin induced acidosis in geriatrics patients with low creatinine clearance.

Safety and radiosensitizing efficacy of sanazole (AK 2123) in oropharyngeal cancers: randomized controlled double blind clinical trial.

UNLABELLED: Oropharynx is an important site of cancer in India. Global comparison indicates higher incidences in India. Radiotherapy remains an important treatment modality. Efforts to improve loco-regional treatment and prolong survival are areas of focus. Radiosensitizers in hypoxic tumors have shown promise. AIM: To study the safety and radiosensitizing efficacy of sanazole in oropharyngeal squamous cell carcinoma (stage T2-4, N0-3, M0) as phase-II double blind controlled trial in patients treated with conventional radiotherapy. SETTINGS AND DESIGN: Single institutional, randomized, double-blind, placebo-controlled trial. MATERIALS AND METHODS: Group 1 (control; n = 23) received normal saline infusion, group 2 (test; n = 23) received sanazole biweekly 1.25 g intravenous infusion 15 minutes before radiotherapy. Surrogate end points of efficacy were tumor and nodal size; safety parameters were mucositis, salivary and skin reactions, dysphagia, vomiting, dysgeusia and neurological deficit. Investigators blinded to the trial evaluated patients, weekly during treatment for six weeks and thereafter monthly for three months. STATISTICAL METHODS: Non-parametric, Friedman's, Chi square, Mann-Whitney U tests. RESULTS: In the test, 15 (65%) patients had complete response, five (22%) partial/no response, two (9%) died, one (4%) lost to follow up. In the control, five (22%) patients had complete response, 16 (70%) partial/no response, one (4%) died, one (4%) lost to follow up. Short-term loco-regional response was better in the test (DF = 3, 95% Confidence Interval 0.418, 0.452, P = 0.0048). In the test group significant vomiting and one case of grade 3 neurological deficit was observed. CONCLUSION: The study validates the usefulness of sanazole for initial loco-regional control in oropharyngeal cancers.

Preclinical evaluation of the antidiabetic effect of Eugenia jambolana seed powder in streptozotocin-diabetic rats.

The world is facing an explosive increase in the incidence of diabetes mellitus and cost-effective complementary therapies are needed. The effects of Eugenia jambolana, a household remedy for diabetes, were studied. Streptozotocin diabetic female albino Wistar rats weighing 150-200 g (N = 6) were fed E. jambolana seed powder (250, 500 or 1000 mg/kg) for 15 days. Diabetic rats fed 500 and 1000 mg/kg seed powder showed an increase in body weight on day 20 in relation to day 5 (6 +/- 4.7, 9 +/- 7.8 vs diabetic control -16 +/- 7.1 g, P < 0.001), a decrease in fasting blood glucose (75 +/- 11.9, 123 +/- 14.4 vs diabetic control -34 +/- 12.1 mg/dl, P < 0.001), a difference in post-treatment fasting and peak blood glucose (38 +/- 11.9, 36 +/- 14.2 vs diabetic control 78 +/- 11.9 mg/dl, P < 0.001), and a difference in liver glycogen (50 +/- 6.8, 52 +/- 7.5 vs normal control 90 +/- 6.6 microg/g of liver tissue, P < 0.001). Tri-terpenoids, tannins, gallic acid, and oxalic acid were the chemical constituents detected in E. jambolana seed. The best results were obtained with an oral dose of 500 mg/kg. Subacute toxicity studies with a single administration of 2.5 and 5.0 g/kg seed powder showed no mortality or abnormality. These data on the antidiabetic effect of E. jambolana seed are adequate for approval of phase 2 clinical trials to evaluate this seed powder as complementary therapy in type 2 and type 1 diabetes.

Preclinical evaluation of the antidiabetic effect of Eugenia jambolana seed powder in streptozotocin-diabetic rats

The world is facing an explosive increase in the incidence of diabetes mellitus and cost-effective complementary therapies are needed. The effects of Eugenia jambolana, a household remedy for diabetes, were studied. Streptozotocin diabetic female albino Wistar rats weighing 150-200 g (N = 6) were fed E. jambolana seed powder (250, 500 or 1000 mg/kg) for 15 days. Diabetic rats fed 500 and 1000 mg/kg seed powder showed an increase in body weight on day 20 in relation to day 5 (6 ± 4.7, 9 ± 7.8 vs diabetic control -16 ± 7.1 g, P < 0.001), a decrease in fasting blood glucose (75 ± 11.9, 123 ± 14.4 vs diabetic control -34 ± 12.1 mg/dl, P < 0.001), a difference in post-treatment fasting and peak blood glucose (38 ± 11.9, 36 ± 14.2 vs diabetic control 78 ± 11.9 mg/dl, P < 0.001), and a difference in liver glycogen (50 ± 6.8, 52 ± 7.5 vs normal control 90 ± 6.6 æg/g of liver tissue, P < 0.001). Tri-terpenoids, tannins, gallic acid, and oxalic acid were the chemical constituents detected in E. jambolana seed. The best results were obtained with an oral dose of 500 mg/kg. Subacute toxicity studies with a single administration of 2.5 and 5.0 g/kg seed powder showed no mortality or abnormality. These data on the antidiabetic effect of E. jambolana seed are adequate for approval of phase 2 clinical trials to evaluate this seed powder as complementary therapy in type 2 and type 1 diabetes.

Comparative evaluation of efficacy and safety profile of three anti-tuberculous regimens in Mangalore.

The aim of our study was to evaluate and compare the therapeutic efficacy & safety profile of three different antituberculous regimens for pulmonary tuberculosis. The study sample size included 90 newly diagnosed, sputum positive patients of pulmonary. tuberculosis. 30 each from different groups. The parameters studied were, therapeutic efficacy included weight gain, cough, sputum examination and safety profile: nausea, vomiting, anorexia, gastritis, hepatitis, jaundice diarrhoea, rashes, dizziness, tingling & numbness, flu like symptoms & joint aches. Group-I showed statistically significant weight gain when compared to Group-II. Improvement in cough and conversion to smear negative were seen in 100% of patients in Group-I, 83.3% of patients in Group-II and 93.3% of patients in Group-III. Therapeutic efficacy was highest with Group I regimen, followed by Group III and Group II which was least efficacious. Group II also registered; the maximum cost and highest incidence of adverse effects.