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Biomedical subjects

P M Bell

Publications and source records attributed to P M Bell.

At least 19 recordsLinked to original sources
PubMed2001

The influence of antifungal drugs on virulence properties of Candida albicans in patients with diabetes mellitus.

OBJECTIVE: This study investigated the influence of nystatin and fluconazole on virulence properties of Candida albicans. STUDY DESIGN: A total of 108 diabetic patients participated in the study. Eighty-eight patients had clinical oral candidosis. Drug therapy was given at 6 hourly intervals for nystatin or daily with fluconazole for a maximum of 2 weeks. Adhesion of C albicans to buccal epithelial cells was determined by using an autologous adhesion assay prospectively over 6 months. Phospholipase production was estimated by using an agar plate method. The data analysis included a paired Student t test and calculation of correlation coefficients. RESULTS: Unlike nystatin, treatment with fluconazole reduced the ability of C albicans to colonize the buccal mucosa for up to 8 weeks after the treatment. Patients without clinical signs of oral candidosis had significantly fewer C albicans isolates producing phospholipase than did patients with oral candidosis. Treatment with fluconazole, but not nystatin, reduced the production of phospholipase from C albicans oral isolates in patients with diabetes mellitus. CONCLUSIONS: In addition to being antifungal, fluconazole alters phospholipase production, modifies buccal epithelial cells, and reduces adhesion of C albicans to human buccal epithelial cells for up to 8 weeks posttreatment in diabetic patients with oral candidosis.

Analysis of Variance↗
PubMed2001

Insulin action and insulin secretion in polycystic ovary syndrome treated with ethinyl oestradiol/cyproterone acetate.

Polycystic ovary syndrome (PCOS) is associated with abnormalities of insulin action and insulin secretion. Ethinyl oestradiol/cyproterone acetate is a common agent used to treat the symptoms of PCOS, but its effects on insulin action and insulin pulsatility have not been examined. We investigated the relationship between insulin action and insulin secretion in 11 patients with PCOS, at diagnosis and after 3 months of treatment with ethinyl oestradiol/cyproterone acetate, and in 13 controls. Insulin action was assessed using the euglycaemic hyperinsulinaemic clamp (2 mU/kg/min for 2 h). Insulin pulsatility was examined over 90 min by 2 min sampling. Short-term insulin pulses were identified using PULSAR. Treatment with ethinyl oestradiol/cyproterone acetate resulted in significant reductions in testosterone (3.3+/-0.7 vs. 1.9+/-0.2 nmol/l, p<0.05), free androgen index (10.2+/-0.7 vs. 1.2+/-0.2, p<0.05) and LH/FSH ratio (2.6+/-0.5 vs. 1.0+/-0.2, p<0.05). During hyperinsulinaemic clamps, the glucose infusion rate (GIR) required to maintain euglycaemia was lower in PCOS compared to controls (33.6+/-2.7 vs. 45.1+/-3.5 micromol/kg/min, p<0.05) but similar in PCOS before and after treatment (33.6+/-2.8 vs. 33.6+/-2.7 micromol/kg/min, p=0.9). Numbers of pulses identified in PCOS and controls were similar and unaltered by ethinyl oestradiol/cyproterone acetate. There was no correlation between GIR and frequency of insulin pulses in PCOS before or after treatment (r=0.2, p=0.6; post r=-0.5, p=0.1) unlike controls (r=-0.6, p=0.04). Despite considerable improvement in androgen profile, treatment with ethinyl oestradiol/cyproterone acetate did not alter insulin action in PCOS, and this insulin resistance does not appear to be determined by insulin pulse frequency.

Adult↗
PubMed2000

Isolation of C. dubliniensis from insulin-using diabetes mellitus patients.

The identification of the novel candidal species, C. dubliniensis, from oral swab studies of HIV-seropositive and -seronegative individuals has led to speculation that such a species may also reside in the oral cavity of other patient groups. In this study involvement of the newly described species, C. dubliniensis, was investigated in oral carriage and disease in 414 insulin-using diabetes mellitus patients. Seventy-seven percent of the diabetic patients carried candidal species in the oral cavity. C. albicans was the most commonly identified candidal species. This was followed by C. dubliniensis, which was isolated on 64 occasions. Colonisation with multiple candidal species was common, and C. dubliniensis was present in both carriage and disease states. Seven patients without signs of oral disease had C. dubliniensis isolated as the sole candidal species, while the same species was associated with various forms of oral candidosis in six patients.

Candida↗
PubMed2000

Comparison of one week 0900 h serum cortisol, low and standard dose synacthen tests with a 4 to 6 week insulin hypoglycaemia test after pituitary surgery in assessing HPA axis.

OBJECTIVE: To compare the use of 0900 h serum cortisol and both low and standard dose Synacthen tests, one week after pituitary surgery with an insulin hypoglycaemia test performed 4-6 weeks after surgery in assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis. DESIGN: 0900 h basal serum cortisol was measured on days 6 and 7 after pituitary surgery (24 h off replacement hydrocortisone) followed by a low dose Synacthen test (1 microg intravenously) on day 6 and a standard dose Synacthen test (250 microg intramuscularly) on day 7. Three to 5 weeks later an insulin hypoglycaemia test was performed on all patients. Both low and standard dose Synacthen tests were performed on control subjects using an identical protocol. SUBJECTS: Forty-two patients (21 male, 21 female), median age 49 years (range 23-73) who had pituitary surgery (Cushing's disease excluded). One patient had undergone repeat surgery for residual tumour and was studied following each operation. Sixteen healthy normal volunteers, median age 37 years (range 21-55). MEASUREMENTS: Serum cortisol measured by radioimmunoassay. RESULTS: Two standard deviations below the mean serum cortisol (logarithmic transformation) in the normal volunteers 30 minutes after low dose Synacthen (1 microg) was 496 nmol/l and after standard dose Synacthen (250 microg) was 504 nmol/l. A normal response was therefore taken as serum cortisol > 500 nmol/l at 30 minutes in both tests (using 496 and 504 nmol/l did not alter results). 0900 h serum cortisols 1 week after surgery were > 250 nmol/l in 31 patients and 29 of these had a normal response to hypoglycaemia (peak serum cortisol > 550 nmol/l). Of the remaining two patients, one had 0900 h serum cortisol on day 6 and 7 after surgery of 405 and 441 nmol/l with a peak serum cortisol response to hypoglycaemia of 451 nmol/l; the other patient had 0900 h serum cortisols of 416 and 251 nmol/l and a peak cortisol response to hypoglycaemia of 498 nmol/l. All eight patients who had a 0900 h serum cortisol < 100 nmol/l failed a subsequent insulin hypoglycaemia test. Seven discrepancies were noted between the low dose Synacthen test and the insulin hypoglycaemia test in the 41 patients who had both tests. In six of these, a subnormal response to low dose Synacthen was followed by a normal response to hypoglycaemia. Three discrepancies were noted between the standard dose Synacthen test and the insulin hypoglycaemia test in the 40 patients who had both tests. In all three cases a normal response to Synacthen was followed by a subnormal response to hypoglycaemia. CONCLUSIONS: A 0900 h serum cortisol < 100 nmol/l (24 h off replacement hydrocortisone) indicated ACTH deficiency and need for lifelong steroid replacement. A 0900 h serum cortisol > 450 nmol/l one week after pituitary surgery is highly suggestive of a normal cortisol response to hypoglycaemia. A 0900 h serum cortisol between 250 and 450 nmol/l one week after pituitary surgery permits safe withdrawal of steroid therapy pending an insulin hypoglycaemia test 1 month after surgery. Patients with 0900 h serum cortisol between 100 and 250 nmol/l should continue replacement steroids until definitive testing. Low dose and standard dose Synacthen tests 1 week after pituitary surgery are unreliable and should not be used.

Adenoma↗
PubMed2000

Insulin resistance and insulin pulsatility in essential hypertension.

OBJECTIVE: Studies in normal humans and in patients with type 2 diabetes mellitus have demonstrated a close inverse relationship between peripheral insulin sensitivity and the frequency of short-term insulin secretory pulses in the systemic circulation. Our objective was to study this relationship in essential hypertension. DESIGN: Study of insulin sensitivity and insulin pulse characteristics in hypertensive subjects and normotensive controls using well-established techniques. METHODS: Twelve subjects with essential hypertension and 12 age- and sex-matched normotensive controls were recruited. Insulin action was measured using the glucose clamp technique combined with isotope dilution methodology. Insulin pulsatility in the peripheral circulation was assessed by sampling every 2 min for 90 min after an overnight fast Pulses were identified using the computer program Pulsar. RESULTS: Insulin sensitivity index (glucose infusion rate/ serum insulin) was lower in the hypertensive patients (P= 0.01) and fasting insulin was increased (P= 0.008) compared to controls. The frequency and amplitude of insulin pulses were similar in the two groups. Insulin pulse frequency and insulin sensitivity were inversely related in the normotensive group (r= -0.68, P= 0.015), but not in the hypertensive group (r= -0.23, P= 0.48). Insulin clearance was reduced in the hypertensive group (P= 0.03), and was inversely related to insulin pulse frequency in the two groups combined (r = -0.51, P= 0.01). CONCLUSIONS: Insulin action was not related to insulin pulse frequency in essential hypertension, in contrast to the situation in normal man.

Adult↗
PubMed1999

Low dose bendrofluazide (1.25 mg) effectively lowers blood pressure over 24 h: results of a randomized, double-blind, placebo-controlled crossover study.

Previous studies indicate that low dose bendrofluazide (1.25 mg/day) has no deleterious effect on insulin sensitivity in contrast to conventional doses. To evaluate the antihypertensive effect of 1.25 mg bendrofluazide across 24 h, we studied 12 subjects in a randomized, double blind, cross-over trial, comprising 8 weeks of either 1.25 mg/day bendrofluazide or placebo. Twenty-four-hour blood pressure averages were significantly lower after bendrofluazide compared with placebo (systolic 125 +/- 4 v 136 +/- 3 mm Hg, P < .005; diastolic: 78 +/- 2 v 85 +/- 2 mm Hg, P < .01). Trough:peak ratios were 0.67 +/- 0.07 for systolic and 0.72 +/- 0.15 for diastolic blood pressure reduction. In conclusion, 1.25 mg bendrofluazide daily produced a useful antihypertensive effect across the full 24-h period.

Aged↗
PubMed1999

A comparison of the naloxone test with the insulin stress test in patients following transsphenoidal surgery.

OBJECTIVE: To study the reliability of the naloxone test in assessing the hypothalamic-pituitary-adrenal (HPA) axis in patients following transsphenoidal pituitary surgery, by comparison with the insulin stress test (IST). Also, to establish a normal range for the response to naloxone in healthy controls. DESIGN: All patients had the IST performed, soluble insulin 0.1-0.3 U/kg (usually 0.15 U/kg) being administered intravenously, followed by venous sampling for plasma glucose and serum cortisol at 0, 15, 30, 45, 60, 75 and 90 minutes. Naloxone (125 micrograms/kg body weight) was similarly administered to all patients 6 days later, with sampling at -15, 0, 15, 30, 45, 60, 90 and 120 minutes for plasma glucose, serum cortisol and plasma ACTH. The naloxone test was also performed on control subjects using an identical protocol. SUBJECTS: Twenty patients (11F/9M) aged 48.8 +/- 2.8 years (mean +/- SE) 4-6 weeks following transsphenoidal pituitary surgery. Twelve normal healthy control subjects (6F/6M) aged 31.5 +/- 3.0 years. MEASUREMENTS: Serum cortisol was measured by radioimmunoassay and plasma ACTH by immunoradiometric assay. RESULTS: Adequate hypoglycaemia (< or = 2.0 mmol/l) was achieved in all patients. Peak cortisol was > 550 nmol/l in 17 subjects (range: 572-867 nmol/l) and a subnormal response observed in 3 (peak cortisol 163-498 nmol/l). In the 17 patients with a normal cortisol response to hypoglycaemia the response to naloxone was extremely variable, with serum cortisol falling in 4 and an increment of < or = 100 nmol/l in 6 others. In the 3 patients who failed the IST, two responded to naloxone and one did not. In normal controls, 3 of the 12 had little or no response to naloxone. CONCLUSIONS: As the naloxone test fails to produce a response in all normal subjects it is impossible to define a 'normal' response. The numerous discrepancies with the IST in patients are further evidence of the test's lack of reliability in assessing the HPA-axis and it is consequently not a viable alternative to traditional dynamic methods such as the IST.

Adrenocorticotropic Hormone↗
PubMed1999

Comparison of effects of captopril used either alone or in combination with a thiazide diuretic on insulin action in hypertensive Type 2 diabetic patients: a double-blind crossover study.

AIMS: It has been suggested that the adverse metabolic effects of antihypertensive therapy offset some of the benefits of blood pressure reduction. It has also been suggested that angiotensin converting enzyme (ACE) inhibitors reduce insulin resistance and that, if used together with thiazide diuretics, the adverse effects of thiazides on insulin sensitivity may be eliminated. We examined the effects on insulin sensitivity of captopril either alone or in combination with bendrofluazide in 11 hypertensive Type 2 diabetic patients. METHODS: Insulin action was assessed using an isoglycaemic hyperinsulinaemic clamp in a double-blind, randomized, crossover study after a 6-week placebo run-in and following two 12-week treatment periods with captopril (C) (100 mg) alone or in combination with bendrofluazide (CB) (2.5 mg). RESULTS: Blood pressure was lower following CB compared to C (128/82 vs. 144/ 88 mmHg; P<0.005) and both were lower than baseline (162/101 mmHg; P < 0.001). CB resulted in a significant increase in fasting plasma glucose compared to C (9.7+/-0.8 vs. 8.5+/-0.6 mmol/; P < 0.05). Exogenous glucose infusion rates required to maintain isoglycaemia during hyperinsulinaemia were lower after CB compared to C (22.3+/-2.4 vs. 27.4+/-4.2 mol x kg(-1) x min(-1); P < 0.05). Suppression of endogenous glucose production was reduced after CB compared to baseline (4.0+/-0.6 vs. 2.4+/-0.5 mol x kg(-1) x min(-1); P< 0.05). CONCLUSIONS: Combination of bendrofluazide with captopril lowered blood pressure but resulted in deleterious effects on insulin action compared to captopril alone.

Antihypertensive Agents↗
PubMed1999

Oral candidal carriage and infection in insulin-treated diabetic patients.

AIM: To evaluate candidal load and carriage of candidal species in 414 insulin-treated diabetes mellitus patients with and without clinical signs of infection. Host factors that could influence candidal load in diabetic patients with oral candidosis were also investigated. METHODS: Candidal species were recovered from 414 insulin-treated diabetes mellitus patients attending two hospital diabetic clinics, using an oral rinse technique. RESULTS: Seventy-seven per cent of diabetic patients carried Candida species in their oral cavity, with C. albicans being the species most frequently isolated. C. dubliniensis was found for the first time in this patient group. Forty per cent of patients colonized with candidal species had no clinical signs of oral candidosis. Where oral candidosis was present, erythematous candidosis was the most common clinical presentation. Candidal load was not associated with age, sex or glycaemic control. However, it was significantly increased in those patients who were tobacco smokers, and non-significantly increased in those patients who wore dentures, or who had clinical signs of oral candidosis. CONCLUSION: The epidemiology of oral candidal carriage and infections in diabetic patients is complex and includes species which have not been previously reported in this group of patients. The development of oral candidosis in insulin-treated diabetes mellitus patients is not the result of a single entity, but rather, a combination of risk factors.

Analysis of Variance↗
PubMed1999

Basal nitric oxide production is impaired in offspring of patients with essential hypertension.

There is considerable evidence that endothelium-dependent nitric oxide (NO)-mediated vasodilatation in response to acetylcholine is impaired in essential hypertension, whereas the endothelium-independent response to sodium nitroprusside is normal. More limited data have suggested that there is also reduced vasoconstriction in response to N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of basal NO release. As it is not known whether endothelial dysfunction in hypertension, if indeed present, is a cause or consequence of the condition, we have studied the normotensive offspring of parents with essential hypertension. Both basal and stimulated vascular responses were examined in 12 normotensive offspring [mean age (+/-S.E.M.) 26.1+/-1.4 years] of parents with essential hypertension and compared with those in 12 age-matched offspring (mean age 25.6+/-1.1 years) of normotensive subjects. Forearm blood flow was measured simultaneously in both arms by venous occlusion plethysmography, both at baseline and during intra-arterial brachial infusion of increasing doses of acetylcholine, sodium nitroprusside, noradrenaline and L-NMMA. There were no significant differences between the groups in the responses to acetylcholine, sodium nitroprusside or noradrenaline. In contrast, the vasoconstrictor response to L-NMMA was significantly blunted in the offspring of hypertensive parents compared with that in the offspring of normotensive parents (P=0.005). Thus endothelial dysfunction, as demonstrated by impaired basal production of NO, is present in subjects at high risk of essential hypertension, and does not occur simply as a consequence of the condition.

Acetylcholine↗
PubMed1998

Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study.

Secondary failure of plasma glucose control following initial successful response to diet therapy may be due to dietary indiscretion, or to progression of the intrinsic diabetic condition. We report a 10-year prospective natural history study of 432 newly diagnosed diabetic patients aged 40-69 years undertaken to assess the effect of intensive dietary management, where patients were transferred to insulin, or oral hypoglycaemic therapy (tolbutamide, metformin) by predetermined criteria of weight and plasma glucose. Secondary failure to diet therapy occurred in 41 patients in years 2-4, 67 patients in years 5-7, and 51 patients in years 8-10; 173 patients remained on diet alone until death or the end of the study. Continuation on diet alone was associated with a lower ongoing fasting plasma glucose, greater beta-cell function assessed by an oral glucose tolerance test at 6 months, and increasing age. The rate of rise of fasting plasma glucose was inversely related to the duration of successful dietary therapy, but mean weight remained constant in all groups while on diet alone. The ongoing fall in beta-cell function assessed by HOMA modelling closely mirrored the progressive rise in fasting plasma glucose: there was no change in mean insulin sensitivity in any of the groups.

Adult↗
PubMed1998

Effects of combination therapy with an angiotensin converting enzyme inhibitor and thiazide diuretic on insulin action in essential hypertension.

OBJECTIVE: To determine whether combination of an angiotensin converting enzyme inhibitor with a high dose of thiazide diuretic avoids adverse metabolic consequences of thiazide diuretics. DESIGN: Double-blind randomized crossover study of two 12-week treatment periods with captopril (up to 100 mg/day) either alone or in combination with 5 mg bendrofluazide given after a 6-week placebo run-in period. Treatment periods were separated by a 6-week placebo washout period. SETTING: Outpatient clinics in greater Belfast. PATIENTS: Fifteen white non-diabetic essential hypertensives (seven male) aged < 65 years recruited from general practices in greater Belfast. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures and peripheral and hepatic insulin action. RESULTS: Two patients failed to complete the study. Blood pressure was lowered (139/89+/-18/7 mmHg combination versus 160/97+/-21/7 mmHg captopril; P < 0.001). Fasting insulin level was raised (7.9+/-3.6 mU/l combination versus 6.2+/-3.2 mU/l baseline; P < 0.001). There were no differences between treatments for glucose, urate, cholesterol and triglyceride levels. Serum potassium level was lowered (3.8+/-0.4 mmol/l combination versus 4.2+/-0.4 mmol/l captopril, P < 0.05). Postabsorptive endogenous glucose production was raised (10.8+/-1.7 micromol/kg per min combination versus 10.0+/-1.5 micromol/kg per min captopril; P < 0.01) and was greater than baseline (9.7+/-2.1 micromol/kg per min, P < 0.05). Suppression of glucose production by insulin was similar with both treatments. Exogenous glucose infusion rates required to maintain euglycaemia did not differ (32.4+/-7.6 micromol/kg per min captopril, 32.7+/-6.2 micromol/kg per min combination, 31.5+/-7.2 micromol/kg per min baseline). CONCLUSIONS: Combination therapy increased glucose production (compared with captopril alone), indicating hepatic insulin resistance. It cannot be assumed that combined preparations with angiotensin converting enzyme inhibitors will ameliorate adverse effects of high doses of thiazide diuretics on insulin action.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Captopril does not improve insulin action in essential hypertension: a double-blind placebo-controlled study.

OBJECTIVE: To compare the effect of captopril with that of placebo on peripheral and hepatic insulin action in essential hypertension, in light of evidence that insulin resistance is associated with cardiovascular risk. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial, with 8 week treatment periods of captopril and placebo preceded and separated by 6 weeks of placebo. SETTING: Belfast teaching hospital. PATIENTS: Eighteen Caucasian nondiabetic patients (10 males), aged under 65 years, with essential hypertension, recruited from general practices in the greater Belfast area. INTERVENTIONS: Captopril at 50 mg twice a day or placebo twice a day for two 8 week treatment periods. MAIN OUTCOME MEASURES: Peripheral and hepatic insulin sensitivity assessed by glucose clamps. RESULTS: Fourteen patients completed the study. Mean (+/- SEM) levels of fasting glucose, fasting insulin and postabsorptive hepatic glucose production were similar after captopril and placebo (5.4+/-0.1 versus 5.4+/-0.1 mmol/l, 10.6+/-2.2 versus 9.5+/-1.1 mU/l, 11.2+/-0.6 versus 11.0+/-0.5 mmol/kg per min, respectively). During hyperinsulinaemia, hepatic glucose production was suppressed to comparable levels after both treatments (4.8+/-0.6 versus 4.3+/-0.6 mmol/kg per min) and exogenous glucose infusion rates required to maintain euglycaemia were also similar (30.0+/-2.6 versus 30.3+/-2.6 mmol/kg per min). CONCLUSION: Captopril therapy in uncomplicated essential hypertension has no effect on peripheral or hepatic insulin sensitivity.

Antihypertensive Agents↗
PubMed1997

Phylogenetic survey of soluble saxitoxin-binding activity in pursuit of the function and molecular evolution of saxiphilin, a relative of transferrin.

Saxiphilin is a soluble protein of unknown function which binds the neurotoxin, saxitoxin (STX), with high affinity. Molecular characterization of saxiphilin from the North American bullfrog, Rana catesbeiana, has previously shown that it is a member of the transferrin family. In this study we surveyed various animal species to investigate the phylogenetic distribution of saxiphilin, as detected by the presence of soluble [3H]STX binding activity in plasma, haemolymph or tissue extracts. We found that saxiphilin activity is readily detectable in a wide variety of arthropods, fish, amphibians, and reptiles. The pharmacological characteristics of [3H]STX binding activity in phylogenetically diverse species indicates that a protein homologous to bullfrog saxiphilin is likely to be constitutively expressed in many ectothermic animals. The results suggest that the saxiphilin gene is evolutionarily as old as an ancestral gene encoding bilobed transferrin, an Fe(2+)-binding and transport protein which has been identified in several arthropods and all the vertebrates which have been studied.

Amphibian Proteins↗
PubMed1997

Macrovascular disease and hyperglycaemia: 10-year survival analysis in Type 2 diabetes mellitus: the Belfast Diet Study.

The relationship between macrovascular disease and blood glucose control in long-term follow-up of Type 2 (non-insulin-dependent) diabetes mellitus is difficult to study because of the gradual rise in fasting plasma glucose due to ongoing beta-cell failure. We used time-dependent covariates in Cox's proportional hazards model to allow variables measured annually during a 10-year prospective follow-up to be related to risk of myocardial infarction or cerebrovascular accident. Data for 432 newly diagnosed diabetic patients were available, 112 of whom suffered myocardial infarction (fatal or non-fatal). Analysis of baseline measurements only gave relative hazards (95% CL) of 1.04 (0.99, 1.09) per mmol l(-1) increase in fasting plasma glucose, 1.43 (1.12, 1.83) per decade increase in age and 1.07 (0.98, 1.17) per 10 % increase in percentage of ideal weight. Analysis incorporating ongoing measurements gave corresponding figures of 1.07 (1.02, 1.12) for fasting plasma glucose, 1.64 (1.23, 2.20) for age and 1.06 (0.95, 1.18) for percentage of ideal weight. The risk of myocardial infarction while on insulin treatment 1.09 (0.58, 2.06) or oral agents 1.41 (0.86, 2.31) was not significantly elevated relative to dietary treatment. Baseline smoking status, systolic blood pressure, and previous myocardial infarction were also significant predictors of myocardial infarction. Similar relationships were found for cerebrovascular accident and total mortality. Increasing fasting plasma glucose is a significant independent predictor of macrovascular disease in diabetes.

Adult↗
PubMed1997

Metformin.

Metformin, a dimethylbiguanide, was first synthesized in 1929 and was shown to be a potent hypoglycemic agent. It was rediscovered in 1957 and was widely used in Europe to treat obese type II patients. Metformin resurfaced in the 1980s and was shown to increase insulin sensitivity; this has led to its introduction to clinical practice in the United States for the first time. The small risk of lactic acidosis is now well documented and appropriate therapeutic guidelines have been established. Metformin is a sage and effective drug for management of non-insulin-dependent diabetes mellitus.

Acidosis, Lactic↗