Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dexfenfluramine has been shown to promote weight loss in overweight people. The present double-blind study was designed to test whether the addition of dexfenfluramine to conventional oral hypoglycaemic treatment would promote weight loss and improve blood glucose control in overweight patients with Type 2 diabetes. The 34 patients studied were randomly assigned to dexfenfluramine or placebo therapy which was added for 12 weeks to their existing treatment regimens of metformin with or without a sulphonylurea. Dexfenfluramine treatment was associated with a significant reduction in weight (98.7 +/- 5.0 (+/- SE) vs 94.9 +/- 5.2 kg; p less than 0.001), BMI (35.0 +/- 1.2 vs 33.6 +/- 1.9 kg m-2; p less than 0.001), HbA1c (7.5 +/- 0.3 vs 6.3 +/- 0.2%; p less than 0.001), fructosamine (313.9 +/- 17.6 vs 274.3 +/- 10.4 mumol l-1; p less than 0.01), systolic (137 +/- 5 vs 128 +/- 6 mmHg; p less than 0.05), and diastolic blood pressure (85 +/- 2 vs 73 +/- 3 mmHg; p less than 0.001). At the end of the study period, the dexfenfluramine treated group had a significantly lower HbA1c (6.3 +/- 0.2 vs 7.2 +/- 0.4; p less than 0.05), fructosamine level (274.3 +/- 10.4 vs 313.3 +/- 16.1 mumol l-1; p less than 0.05) and diastolic blood pressure (73 +/- 3 vs 81 +/- 3 mmHg; p less than 0.03) when compared with the placebo group. In those patients treated with dexfenfluramine, the reduction in HbA1c and blood pressure did not correlate with the decrease in BMI (r = 0.44 and 0.12, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The effects of dexfenfluramine on blood glucose control in patients with type 2 diabetes. 160 Jul 4

Dexfenfluramine is well known for its weight reducing action and has been reported to improve glycaemic control in obese Type 2 diabetic patients not adequately controlled on conventional oral hypoglycaemic therapy. In this double-blind placebo-controlled study, 20 obese Type 2 diabetic patients with mean HbA1c of 8.8 +/- 0.5% (normal range 3.5-6.0%), and mean body mass index (BMI) of 34.4 +/- 1.0 kg m-2, who were poorly controlled on insulin (mean dosage 58.0 +/- 6.1 units day-1) were randomized to receive either additional dexfenfluramine or placebo for 12 weeks. Seventeen of these patients were already taking maximum tolerated metformin therapy (mean dosage 1.6 +/- 0.2 g day-1) and the other three were unable to tolerate any at all. At baseline, the dexfenfluramine and placebo groups were similar in all parameters studied. After the 12-week treatment period, median HbA1c had fallen in dexfenfluramine treated patients from 8.5 (interquartile range (IR): 7.5-10.3) to 7.1% (IR: 6.7-7.5; p < 0.02). The fall in HbA1c in individual patients after treatment with dexfenfluramine was strongly associated with weight loss (r = 0.69; p < 0.04), although as a group the changes in weight and BMI were not statistically significant. Placebo was without effect. These results show that in the obese patient with Type 2 diabetes who is poorly controlled despite large daily doses of insulin and metformin, adjunctive dexfenfluramine can improve glycaemic control without exacerbating weight gain.
 ...
PMID:Obese patients with type 2 diabetes poorly controlled by insulin and metformin: effects of adjunctive dexfenfluramine therapy on glycaemic control. 795 98

Dexfenfluramine has been shown to lower blood glucose concentrations independently of its effects in reducing food intake and body weight, in human and animal syndromes of non-insulin dependent diabetes. This study aimed to determine whether dexfenfluramine could also reduce glycaemia in rats with severe insulin-deficient diabetes induced by the beta-cell toxin, streptozotocin (55 mg kg-1). Three weeks after diabetes induction, nine groups (each n = 10) of diabetic and non-diabetic rats underwent oral glucose tolerance tests (1 g kg-1, by gavage). These tests were preceded by 12-18 h of fasting to remove the confounding effects of hyperphagia in diabetic rats, and to stabilize glycaemia. Dexfenfluramine (1.0 mg kg-1), given 2 h before the glucose challenge, significantly reduced basal glycaemia and decreased the post-challenge glycaemic rise (P < 0.01 vs. untreated diabetics). Dexfenfluramine dosages of 2.5 and 5.0 mg kg-1 both further flattened the post-challenge glycaemic profiles (both P < 0.01 vs. untreated diabetics) and achieved levels that did not differ significantly from those in non-diabetics (both P > 0.05). Subsequently, the studies using dexfenfluramine dosages of 2.5 and 5.0 mg kg-1 were repeated to determine whether the drug affected plasma insulin levels 2 h after dosing. In diabetic rats, plasma insulin concentrations were reduced to 10-20% of non-diabetic values, and were not significantly altered by dexfenfluramine. Acute dexfenfluramine administration therefore improves and (at dosages of 2.5 and 5.0 mg kg-1) essentially normalizes glucose tolerance in rats with severe insulin-deficient diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Acute dexfenfluramine administration normalizes glucose tolerance in rats with insulin-deficient diabetes. 803 52

This study investigated the potential for dexfenfluramine to improve biochemical and clinical risk factors for cardiovascular disease, in obese dyslipidaemic individuals. Dexfenfluramine, the dextro isomer of fenfluramine, has been shown to aid weight reduction and lower blood lipids in normal subjects, and to improve glucose tolerance and insulin sensitivity in subjects with diabetes mellitus. Twenty-nine overweight (mean weight 83.3 +/- 11.3 kg), hyperlipidaemic (mean total cholesterol 7.3 +/- 1.2 mol/l) subjects participated in a 12-week randomized double-blind parallel study of dexfenfluramine versus placebo. After an eight-week dietary run-in phase, subjects were randomised to treatment with either dexfenfluramine or placebo for 12 weeks. During the run-in, energy intakes fell in both groups (5.5% for dexfenfluramine, 5% for placebo, no significant difference between groups). Dietary composition improved, fat as a percentage of energy decreased (14%, P < 0.001, for dexfenfluramine; 11.7%, P < 0.05, for placebo), and carbohydrate increased (8.5%, P < 0.05, for dexfenfluramine; 5.6%, not significant, for placebo). During the treatment period, energy intakes in the dexfenfluramine group were further reduced by 7.5%, whereas there was no change in the placebo group (P = 0.02 between dexfenfluramine and placebo groups); however, nutrient composition remained constant for both groups. Side-effects were formally reported by 40% of subjects during the initial four weeks' treatment with dexfenfluramine with three subjects withdrawing from the study. Side-effects were largely resolved by week 4. Both groups lost weight similarly during the run-in but there were no significant changes in any biochemical parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Dexfenfluramine reduces cardiovascular risk factors. 804 93

Dexfenfluramine, a serotonin agonist with effects on the central nervous system (CNS), lowers blood glucose in patients with non-insulin-dependent mellitus (NIDDM). Previous studies using the hyperinsulinemic clamp have shown that dexfenfluramine improves insulin action on both stimulation of glucose uptake and inhibition of hepatic glucose production (HGP). Since the central nervous system can influence glucose tolerance in ways that may not be detected using a clamp procedure, we investigated the effects of dexfenfluramine on glucose kinetics during an oral glucose tolerance test (OGTT) in patients with NIDDM. Glucose kinetics were measured basally and during an OGTT using a double isotope technique and the modified one-pool model of the glucose system. After a 4-week run-in period, studies were performed before, after two 15 mg doses, and then after 4 weeks on 15 mg twice daily in 10 subjects with NIDDM. Fasting-plasma glucose was significantly lower after 4 weeks on dexfenfluramine (P < 0.01) as was plasma glucose at both 1 and 2 h during the OGTT (P < 0.05). The lower plasma glucose was associated with a reduction in HGP both basally (P < 0.01) and during the 1st hour of the OGTT (P < 0.05). There was no change in peripheral glucose uptake. Plasma insulin levels were unaltered, but plasma glucagon was lower after 1 month of treatment. We conclude that dexfenfluramine improves fasting-blood glucose and oral glucose tolerance predominantly by reducing hepatic glucose production.
Diabetes Res Clin Pract 1994 Mar
PMID:Effects of dexfenfluramine on glucose turnover in non-insulin-dependent diabetes mellitus. 807 Mar 4

Dexfenfluramine increases serotonergic activity by stimulating serotonin (5-hydroxytryptamine; 5-HT) release into brain synapses, inhibiting its reuptake into presynaptic neurons and by directly stimulating postsynaptic serotonin receptors. On the basis of the serotonin hypothesis of appetite control, these actions would be expected to reduce appetite and, consequently, bodyweight. Studies conducted in animals and in overweight patients with and without associated disorders have confirmed the weight-reducing efficacy and good tolerability of dexfenfluramine. In 3-month clinical studies in obese patients, weight reductions with dexfenfluramine 15mg twice daily combined with dietary support were significantly higher than those achieved with placebo and similar to those with ephedrine/caffeine 20/20mg 3 times daily, sibutramine 10mg once daily and fluoxetine 60 mg/day. Furthermore, dexfenfluramine recipients with non-insulin-dependent diabetes mellitus, hyperlipidaemia or hypertension consistently show improvements in glycaemic control, blood lipid profiles and blood pressure. 12-month trial results indicate that most weight loss occurs in the initial 6 months and appears to be maintained for a further 6 months. Weight regain after withdrawal of treatment in 12-month studies demonstrates that dexfenfluramine is effective in maintaining a stable bodyweight at a lower level than placebo and in limiting food intake over this time period. Commonly reported adverse events with dexfenfluramine include diarrhoea, tiredness, dry mouth and somnolence; these symptoms are generally mild and transient. Approximately 7 and 10% of dexfenfluramine recipients in short and long term studies withdrew because of adverse events. Dexfenfluramine was better tolerated than ephedrine/caffeine and fluoxetine in short term studies. Obesity is a chronic condition that is accompanied by a number of metabolic complications. It is a significant health problem in developed countries, and as a major risk factor for many chronic diseases, including diabetes and cardiovascular disease, the economic burden of this condition is considerable. As with other chronic conditions, there is a role for pharmacological intervention in patients with severe obesity. However, drugs should be considered as only one component of a weight-control programme, since additional lifestyle modification is required to maintain weight loss. The promising data on the long term efficacy and tolerability of dexfenfluramine as well as its favourable effects on risk factors associated with obesity requires confirmation in long term studies. In the meantime, dexfenfluramine should be considered a valuable adjunct to a reduced-calorie diet in the management of severe obesity, particularly in patients with associated disorders and those unsuccessful with conventional weight loss measures. Available data support the use of the drug for up to 1 year to maintain weight loss and thus dexfenfluramine should be considered for long term administration.
 ...
PMID:Dexfenfluramine. An updated review of its therapeutic use in the management of obesity. 911 19

Dexfenfluramine (DF) is contraindicated in severe psychiatric disorders and in depression. We used DF in 3 patients with chronic psychosis and severe overeating without changes in psychiatric pharmacotherapy. Two patients had paranoid schizophrenic psychosis with hallucinations, one patient mixed psychosis, beginning with lactation psychosis, and several attacks of hallucinations and depression later. Overeating was removed in all 3 patients without any negative effect on the psychotic state. All patients were able to maintain their body weight. Two patients with poorly controlled diabetes improved markedly their metabolic status. Doses up to 75 mg per day of DF were necessary during binge eating episodes in one patient. We conclude that DF can be used with care under close psychiatric supervision in psychotic patients with severe overeating.
 ...
PMID:Dexfenfluramine in psychotic patients. 974 Oct 46

Obesity is common in non-insulin-dependent diabetes mellitus (NIDDM) patients; in Singapore in a cohort of 314 diabetics, 44.3% were overweight. Management of obesity in diabetics differs from that in non-diabetics in that it is more urgent; weight maintenance is more difficult and hypoglycaemic medication may cause weight changes. However, like in the non-diabetic, management of obesity in the diabetic requires a pragmatic and realistic approach. A team approach is required: the help of a nurse educator, a dietitian, behaviour modification therapist, exercise therapist and others are required. A detailed history, careful physical examination and relevant investigations are required to assess the severity of the diabetic state and to exclude an occasional underlying cause of the obesity in the obese NIDDM patient. Weight loss is urgent in the obese NIDDM patient, especially for those with android obesity. There must be a reduction in energy intake. Weight loss leads to an improvement in glucose tolerance and in insulin sensitivity, as well as to a reduction in lipid levels and to a fall in blood pressure in the hypertensive. Exercise is of limited short-term value measured in terms of weight reduction, except in the younger obese NIDDM patient; but it does allow improvement in overall metabolic control and, long-term, is critical for preferred weight maintenance. The biguanide, Metformin, is the hypoglycaemic drug of choice as it leads to consistent weight reduction. The sulphonylureas may cause weight gain. Insulin should be avoided where possible as it causes further weight gain. Other hypoglycaemic agents include Glucobay (alpha-glucosidase inhibitor) and Troglitazone (insulin sensitizer) which do not alter the weight. Orlistat (lipase inhibitor) is promising as it causes reduction of weight, blood glucose and lipid levels. Anti-obesity drugs (noradrenergic and serotonergic agents) have modest effects on weight reduction in the obese NIDDM patient; a widely-used preparation, Dexfenfluramine (Adifax), has been withdrawn because of side-effects. Surgery such as gastric plication is the last resort in treating the morbidly obese NIDDM patient. Against this background, the institution of life-long food and exercise habits which favour health, body composition and fat distribution are paramount in the prevention and minimization of expression of NIDDM. The discovery of leptin in 1994 has led to intense research into energy homeostasis in obesity; hopefully this will lead to better treatment of obesity in diabetics and non-diabetics.
...
PMID:Management of obesity in non- insulin- dependent diabetes mellitus. 2439 84