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)

Apolipoproteins B↗

PubMed1993

Noninsulin dependent diabetes mellitus.

Explore the source record for details and available documents.

Coronary Disease↗

PubMed1993

Plasma proinsulin in recently diagnosed type 2 diabetes mellitus.

We measured levels of immunoreactive insulin (IRI) and proinsulin using a sensitive and specific immunoradiometric assay (IRMA), in non-obese recently diagnosed type 2 diabetic subjects. The proinsulin IRMA showed full cross reaction with intact proinsulin, des 31-32 proinsulin and des 64-65 proinsulin, but no reaction with insulin or C-peptide. In a group of 41 recently diagnosed non-obese Caucasian type 2 diabetic subjects (study group), mean fasting proinsulin levels were greater than that of 40 age and body mass index (BMI) matched controls (study group 17.4 +/- 2.0, controls 10.1 +/- 0.9 pmol-1, P < 0.001). Following a standard test meal, 30 and 60 min levels were not significantly different between groups but 90- and 120-min proinsulin levels were elevated in the study group. The maximum proinsulin to IRI ratio was 20% in the fasting state and did not differ between study and control groups. Proinsulin profiles were similar in subjects receiving oral hypoglycaemic agents and those on dietary treatment alone. Proinsulin did not correlate with indices of glycaemic control, total cholesterol, triglycerides or HDL cholesterol, but a relationship was observed with IRI before and after the meal. These results suggest that increased secretion of insulin precursors of low biological activity occurs in non obese recently diagnosed type 2 diabetic subjects under reasonably good glycaemic control; in such individuals the elevated levels of these precursors are approximately in proportion to the increase in IRI and are less than those reported in some previous studies.

Blood Glucose↗

PubMed1993

Treating hypercholesterolaemia with HMG CoA reductase inhibitors: a direct comparison of simvastatin and pravastatin.

BACKGROUND: Simvastatin and pravastatin are both competitive inhibitors of the rate limiting enzyme for cholesterol biosynthesis (HMG CoA) reductase, but data from individual clinical trials suggest significant differences in potency for cholesterol reduction between the two drugs. AIM: To assess any differences in efficacy and safety between simvastatin and pravastatin in a direct, comparative study. METHODS: A double-blind, double-dummy, randomised study design was used, involving 48 patients with primary hypercholesterolaemia. Following a 6 week placebo baseline period, patients were randomly allocated to treatment with either simvastatin or pravastatin, commencing at a dose of 10 mg daily. The dose levels were titrated up to the recommended maximum effective dose of 40 mg daily at 6 weekly intervals if LDL cholesterol levels remained > or = 3.4 mmol/L. After 18 weeks of therapy, all patients were transferred to simvastatin therapy for a further 6 weeks, continuing at their week 18 dose level. Patients complied with a standard lipid lowering diet (containing < 30% of energy as total fat) throughout the study period. RESULTS: Over the 18 week direct comparison of the two drugs, there was a significant difference (p < 0.001) in response between simvastatin and pravastatin for reduction in levels of total cholesterol (32% vs 21% respectively), LDL cholesterol (38% vs 27%) and apolipoprotein B levels (34% vs 23%). No significant difference in drug effect was seen for the small reduction in levels of apolipoprotein AI (5% vs 6% respectively), nor for the increased levels of apolipoprotein AII (14% vs 11%) and HDL cholesterol (11% vs 7%). Lp(a) levels remained unchanged. When pravastatin was replaced with simvastatin for the final 6 weeks of the study in the 23 patients initially randomised to pravastatin, there were further reductions (p < 0.01) in total and LDL cholesterol, and apolipoprotein B. These results establish the advantage of simvastatin over pravastatin in terms of efficacy, for the treatment of primary hypercholesterolaemia.

Adult↗

PubMed1993

Lipid, lipoprotein and apolipoprotein distributions in an elderly New Zealand population.

The aim of this study was to determine the lipid, lipoprotein and apolipoprotein distribution in an ambulant elderly New Zealand population, and to consider the association between these and other variables (including body mass index, diabetes mellitus, and smoking history) with the prevalence of manifest macrovascular disease in a cross-section analysis. The population sample was randomly selected from the age/sex register of a large urban medical centre in Christchurch, New Zealand. A total of 369 subjects (participation rate 69%) aged 65 years and older were screened for manifest macrovascular disease, diabetes mellitus, smoking status, height and body weight. Levels of plasma total cholesterol, triglycerides, HDL cholesterol, apolipoproteins AI and B, glucose, glycated haemoglobin and fibrinogen were measured. Three way analysis of variance (ANOVA) was used to compare continuous variables across age/sex/macrovascular disease groups. Females had significantly higher levels of total and HDL cholesterol, apolipoproteins AI and B than males. Body mass index showed a significant decrease with increasing age. Macrovascular disease was manifest in 24% of males, and in 26% of females. No direct correlation was seen between any of the measured continuous variables and the presence of macrovascular disease, except for fibrinogen (P < 0.05). No significant association was seen between macrovascular disease and smoking status, nor with a diagnosis of diabetes. In females, the frequency of macrovascular disease was significantly higher amongst those with low (< 1.00 mmol/L) levels of HDL.

Age Factors↗

PubMed1993

HLA-DQ beta typing and non-Asp57 alleles in IDDM and nondiabetic subjects in New Zealand.

OBJECTIVE: To determine the frequency of IDDM risk-associated HLA-DQ beta alleles in New Zealanders with IDDM and nondiabetic control subjects, and to examine these as susceptibility markers in relation to IDDM incidence. RESEARCH DESIGN AND METHODS: HLA-DQ beta typing was conducted in 55 juvenile-onset IDDM subjects diagnosed between 1990 and 1992, and 53 nondiabetic control subjects. Allele typing was conducted by a polymerase chain reaction-restriction fragment-length polymorphism technique. All subjects were residents of Canterbury, New Zealand. IDDM incidence data were obtained from the Canterbury, New Zealand, Diabetes Registry. RESULTS: The frequency of the susceptibility genotype DQ beta *0201/0302 was 43.6 and 5.7% in the IDDM and control groups, respectively, reflecting the increased prevalence of allele 0302 in the IDDM group. Alleles 0301, 0501, and 0602.3 were more prevalent in the control group than the IDDM group. The frequency of non-Asp57 alleles was 90.9 and 61.3% in the IDDM and control groups, respectively. Overall, the HLA-DQ beta allele distribution was similar to reports from other Caucasian populations. The 0- to 19-yr age-specific IDDM incidence rate over the period in which the diabetic subjects were diagnosed was 19.5/100,000 person-yr, the highest levels observed in Canterbury over the last decade. Our relatively high background prevalence of non-Asp57 alleles and high IDDM incidence rates were similar to results from some Scandinavian and other hotspot populations. CONCLUSIONS: HLA-DQ beta alleles are genetic susceptibility markers in New Zealand, and other Caucasian populations. Peak IDDM incidence levels observed in 1990-1992 in our population are in accordance with a high background population prevalence of non-Asp57 alleles. These results suggest that the high Canterbury incidence rates may be due to a large HLA-DQ beta non-Asp57 at-risk population.

Alleles↗

PubMed1992

Prevalence of diabetes mellitus in an ambulant elderly New Zealand population.

The prevalence of diabetes mellitus (both known and previously undiagnosed) was studied in a population sample, predominantly Caucasoid and resident in the community with an age/sex distribution representative of the New Zealand population aged 65 + years, using WHO criteria. The population sample was randomly selected from the age/sex register of a large urban medical centre in Christchurch, New Zealand. Three hundred and sixty-nine subjects (participation rate 69.4%) were screened by casual glucose and glycated haemoglobin measurement, followed by oral glucose tolerance testing (OGTT) if one or both were elevated. The minimum prevalence rate of diabetes in the study sample was 17.2 +/- 3.3% in men and 12.5 +/- 2.2% in women (since not all patients underwent OGTT). The rate was only significantly higher in men than women in the 70-74 year age group (P less than 0.01). The combined age-adjusted prevalence rates for the New Zealand elderly are estimated to be 9.9% known diabetes, 5.0% previously undiagnosed, with the total prevalence rate 14.9%. Newly diagnosed subjects had a significantly higher body mass index than known diabetic or non-diabetic subjects (P less than 0.01). Eighty-two percent of newly diagnosed subjects had visited their general practitioner at least once during the previous 6 months. Measurement of glycated haemoglobin had a greater positive predictive value than casual blood glucose in the detection of new cases. There was no difference in frequency of attendance with general practitioners or in hospital admission rates between non-diabetic patients, or those with known or newly diagnosed diabetes. This study suggests that diabetes mellitus may be a prevalent disorder amongst the New Zealand elderly.

Age Factors↗