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The indian diabetes prevention programme shows that lifestyle modification and metformin prevent type 2 diabetes in asian indian subjects with impaired glucose tolerance idpp-1. Metaanalysis. Diabetes Care. 1992; 15: 953-9. Peters AL, Davidson MB. Insulin plus sulfonylurea agent for treating type 2 diabetes. Ann Intern Med. 1991; 115: 45-53. Johnson JL, Wolf SL, Kabadi UM. Efficacy of insulin and sulfonylurea combination therapy in type II diabetes. A meta-analysis of the randomized placebo-controlled trials. Arch Intern Med. 1996; 156: 259-64. Yki-Jarvinen H, Kauppila M, Kujansuu E, Lahti J, Marjanen T, Niskanen L, et al. Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus. N Engl J Med. 1992; 327: 1426-33. Yki-Jarvinen H, Ryysy L, Kauppila M, Kujansuu E, Lahti J, Marjanen T, et al. Effect of obesity on the response to insulin therapy in noninsulindependent diabetes mellitus. J Clin Endocrinol Metab. 1997; 82: 4037-43. Saudek CD, Duckworth WC, Giobbie-Hurder A, Henderson WG, Henry RR, Kelley DE, et al. Implantable insulin pump vs multiple-dose insulin for non-insulin-dependent diabetes mellitus: a randomized clinical trial. Department of Veterans Affairs Implantable Insulin Pump Study Group. JAMA. 1998; 276: 1322-7. Taves DR. Minimization: a new method of assigning patients to treatment and control groups. Clin Pharmacol Ther. 1974; 15: 443-53. Lapidus L, Bengtson C, Larsson B, Pennert K, Rybo E, Sjostrom L. Distribution of adipose tissue and risk of cardiovascular disease and death: a 12 year follow up of participants in the population study of women in Gothenburg, Sweden. Br Med J Clin Res Ed ; . 1984; 289: 1257-61. Desbuquois B, Aurbach GD. Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. J Clin Endocrinol Metab. 1971; 33: 732-8. Gidez LJ, Miller GJ, Burstein M, Eder HA. Analysis of plasma high density lipoprotein subclasses by a precipitation procedure: correlation with preparative and analytical ultracentrifugation. In: Lippel K, ed. Report of the High Density Lipoprotein Methodology Workshop. Bethesda, MD: U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health; 1998: 328-40. NIH publication no. 79-661. 13. Bruce DG, Clark EM, Campbell LV, Chisholm DJ. Insulin therapy in patients with poorly controlled non-insulin-dependent diabetes mellitus. Med J Aust. 1987; 146: 240-2. DeFronzo RA, Goodman AM. Efficacy of metformin in patients with noninsulin-dependent diabetes mellitus. The Multicenter Metfformin Study Group. N Engl J Med. 1995; 333: 541-9. United Kingdom Prospective Diabetes Study UKPDS ; . 13: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. Br Med J. 1995; 310: 83-8. Gutniak M, Karlander SG, Efendic S. Glyburide decreases insulin requirement, increases -cell response to mixed meal, and does not affect insulin sensitivity: effects of short- and long-term combined treatment in secondary failure to sulfonylurea. Diabetes Care. 1987; 10: 545-54. Quatraro A, Consoli G, Ceriello A, Giugliano D. Combined insulin and sulfonylurea therapy in non-insulin-dependent diabetics with secondary failure to oral drugs: a one year follow-up. Diabet Metab. 1986; 12: 315-8. Abraira C, Colwell JA, Nuttall FQ, Savin CT, Nagel NJ, Comstock JP, et al. Veterans Affairs Cooperative Study on glycemic control and complications in type II diabetes VA CSDM ; . Results of the feasibility trial. Veterans Affairs Cooperative Study in Type II Diabetes. Diabetes Care. 1995; 18: 1113-23. UKPDS 28: a randomized trial of efficacy of early addition of metformin in sulfonylurea-treated type 2 diabetes. U.K. Prospective Diabetes Study Group. Diabetes Care. 1998; 21: 87-92. Makimattila S, Nikkila K, Yki-Jarvinen H. Causes of weight gain during insulin therapy with and without metformin in patients with non-insulindependent diabetes mellitus. Diabetologia. [In press]. 21. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993; 329: 977-86.
Maternal mortality is still quite high in Bangladesh despite decades of programmes and activities. Maternal health care coverage depends on availability and utilization of services . With trend of increase in urbanization there is increasing demands for maternity care services . The objective of the study was to assess present status of utilization of the antenatal, childbirth, postnatal and neonatal care services at urban setting. This was a cross sectional descriptive study done during August to December 2001 in the catchment area of randomly selected ten health care centres run by partner NGOs of Urban Primary Health Care Project and Dhaka City Corporation in Dhaka Metropolitan city. A total 3, 000 mothers with under one year child was selected randomly from about 49, 526 households and information were collected by interviewer-administered structured questionnaire. Mean age of respondents was 24.6 5.12 years. Among them, 31.14% were illiterate and 67.87% were multipara. About 87.74% received antenatal care during last pregnancy, of which 23.74% from public sector, 32.63% from NGO and 39.63% from private physicians. Antenatal care was provided by graduate doctors in 51.42% and by paramedics in 29.33%. Institutional delivery was 35% and conducted by a trained person in 39% cases. Reasons for not seeking medical care during pregnancy and delivery were financial difficulties 24.53% ; , no perceived problem 25.16% ; , transportation problems 11.70% ; and fear of Caesarian operation 4.43% ; . Pregnancy and childbirth were perceived to be a natural event and delivery should be done at home. Health centres were thought to be a place for dealing with emergencies and complications only. J Bangladesh Coll Phys Surg 2005; 23 : 54-58.

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Rosiglitazone 1. Fonseca V et al. Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus. A randomised controlled trial. JAMA 2000; 283: 1695-1702. Wolffenbuttel BHR et al. Addition of low-dose rosiglitazone to sulphonylurea therapy improves glycaemic control in type 2 diabetic patients. Diabetes Medicine 2000; 17: 40-47 and isordil. Enables further reinforcement of drug discovery research which starts from natural bioactive substances, state-of-the-art high sensitivity screening approach, structural biology, process research, pharmacokinetics and safety research.
The main drawback of metormin is the high incidence of gastrointestinal side effects of nausea and diarrhoea, together with flatulence, abdominal pain and a metallic taste. Loose bowel movements can be an intermittent rather than a continuous problem. These effects are usually dose-related and transient so it is always worth starting at low dose e.g. 500 mg b.d. with meals ; and gradually increasing e.g. to 1 g b.d. ; after 2 weeks or so. It is sensible to warn all patients about these side effects; approximately 1525% of patients will report some initial gastrointestinal problems if questioned and it seems to be a more frequent problem with women than with men. For some patients around 5% ; , the side effects are so persistent and severe that metfrmin has to be withdrawn. However, many patients will tolerate the drug despite some side effects, and it is worth exploring with the patient the highest tolerable dose. Even lowdose meyformin 500 mg once or twice daily is valuable and can obviously be used in combination with other OHAs and with insulin in type 2 diabetes. The recommended maximal dose is 2550 mg day 850 mg 3 ; , though some clinicians go up to daily for very obese patients e.g. 100 kg ; . Other less common side effects include lactic acidosis see Q. 9.11 ; and decreased vitamin B12 absorption. A former biguanide phenformin was withdrawn some years ago because of the high risk of lactic acidosis and letrozole.

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Able to show a metformin-induced decrease in indices of insulin resistance in patients with PCOS 15 ; . However, resumption of menses shortly after initiation of metformin therapy has been reported in a significant portion of patients with PCOS 4 8 ; . believed that metformin leads to decreases in serum free androgen levels, thus permitting resumption of menstrual cyclicity 2, 4 ; . Our case raises two important issues relevant to the presence of extremely high androgen levels associated with maternal virilization ; during pregnancy: 1 ; the indeterminate, yet existent, risk of masculinization of a female fetus; and 2 ; the risk of metformin therapy during pregnancy. With regard to issue 1, the possibility of fetal masculinization exists in maternal congenital adrenal hyperplasia, maternal ovarian tumors, exogenous androgen administration to the mother, luteoma of pregnancy, and rarely ; in placental aromatase deficiency and in mothers with PCOS 12, 13, 16 ; . The exact incidence of this side effect of maternal androgens varies greatly among case reports and published small series 12, 20, 21 ; . Excess androgen exposure during fetal development is relevant not only to genital differentiation but also to central nervous system functional mechanisms underlying subsequent expression of sociosexual behavior and gender identity 22, 23 ; . Whereas fetal congenital adrenal hyperplasia is the most common cause of ambiguous genitalia in female neonates, luteoma of pregnancy is the most frequent cause for maternal virilization during pregnancy, as approximately 50 60% of female fetuses born to virilized mothers exhibit signs of masculinization 20 ; . Interestingly, virilization of the fetus has not proven to be tightly correlated with maternal androgen levels. In general, such a risk is increased if the mother herself shows clinically significant manifestations of virilization 12 ; . The timing of androgen exposure during gestation has been shown to affect the neonatal phenotype, as expected 12, 13 ; . With regard to issue 2 i.e. the effects of metformin during pregnancy ; , metformin has been rated by the Food and Drug Administration as a category B medication 24 ; . Mouse embryos exposed to metformin at doses of 500 2, 550 mg daily have shown no major malformations in the offspring 25 ; . A South African group has published several series describing women with type II diabetes mellitus on metformin therapy throughout pregnancy; no adverse effects were reported, with regard to fetal and neonatal development 26 ; . In conclusion, we report a case where maternal hyperandrogenism during pregnancy was not attributable to common causes, i.e. ovarian tumor or luteoma of pregnancy which can all be treated effectively, either medically or surgically ; , but rather was due to PCOS. This case is of additional interest because of significant increases in maternal androgen levels at the early stages of pregnancy, a phenomenon that is quite rare in normal pregnancy 27, 28 ; but may be more frequent in PCOS 13 there is a paucity of information with regard to this phenomenon in women with PCOS. Our case suggests that metformin may be effective for anovulatory women with PCOS and extreme hyperandrogenemia. These patients also might be potentially maintained on metformin throughout pregnancy, aiming at the prevention of inadvertent fetal masculinization feto-protective treatment. Action: TZDs activate peroxisome proliferator-activated receptor PPAR ; and thereby regulate a number of genes involved in glucose and lipid metabolism. They act to improve insulin sensitivity. Onset: Both rosiglitazone and pioglitazone are rapidly absorbed and have high bioavailability. The timing of dose in relation to food does not significantly affect absorption or serum levels. Changes in fasting plasma glucose may start to be seen within two weeks, but maximal effects on glycaemic control may not be evident until 614 weeks after commencement of therapy. Dosing: Both rosiglitazone and pioglitazone are available as oral formulation. Rosiglitazone comes in 2 mg, 4 mg and 8 mg tablets and pioglitazone in 15 mg, 30 mg, and 45 mg tablets. No dosage adjustment is required for renal impairment. Recommended dose for rosiglitazone Avandia; GlaxoSmithKline ; -- Commence at 4 mg per day, and, if necessary, increase to 8 mg per day after 68 weeks as a single or divided dose given with or without food. There is no additional benefit from doses higher than 8 mg per day. The largest dose given in combination with sulfonylurea in clinical studies was 2 mg twice daily. Recommended dose for pioglitazone Actos; Eli Lilly ; -- Commence at 15 mg per day, and, if necessary, increase to 30 mg per day up to a maximum of 45 mg per day after 46 weeks. Give as a single dose with or without food. The largest daily dose used in clinical studies of pioglitazone in combination with insulin or sulfonylurea was 30 mg. Metabolism: Both drugs are extensively metabolised by hepatic cytochrome P450. Rosiglitazone metabolites are essentially inactive and mainly excreted in the urine. Some of the pioglitazone metabolites are active and are excreted in faeces and urine. Neither drug inhibits cytochrome P450. Although no significant drug interactions have so far been identified, prescribers should be vigilant for possible interactions, especially with drugs metabolised by or affecting the cytochrome P450 system. Adverse effects: Both drugs are well tolerated. There have been some case reports of hepatic dysfunction in patients taking the two drugs but causation was not definite. The incidence of elevations in enzyme levels on liver function tests was the same in treatment and placebo groups. The most common adverse effects include weight gain, oedema and dilutional anaemia. Because of fluid retention, these drugs may exacerbate heart failure and should not be prescribed to patients with New York Heart Association III-IV cardiac status. The drugs are also contraindicated in pregnancy and lactation and have not been tested in children. In women with polycystic ovarian syndrome with insulin resistance, treatment with these drugs may restore ovulation and appropriate advice regarding contraception should be given. When used in combination with other antidiabetic drugs, rosiglitazone and pioglitazone have been associated with mild hypoglycaemia requiring dose reduction of sulfonylurea, metformin or insulin and levocetirizine. Those data have not yet been reported. Investigators are also following the metformin trial population to determine whether people who continue to use the drug continue to have a lower risk for diabetes. In summary, rosiglitazone is the most efficacious of the drugs, but is also expensive and possibly most harmful. Mdtformin is nearly as effective as rosiglitazone in the most obese patients, is safe and generally well-tolerated with high adherence, and is inexpensive relative to the other drug options. Acarbose, although it is safe, is less effective and is poorly tolerated by many people.

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Follow-up HbA1c values most recent HbA1c obtained at least 2 months after initiation of metformin therapy ; were available for 80% of metformin users with baseline values and for 41% of those not starting metformin. From an analysis of covariance model that excludes patients with baseline serum creatinine levels 1.5 mg dl and adjusts change in HbA1c for age, sex, and baseline HbA1c level!

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