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Q 41What is the optimum method of management of abnormalities in lipid control in adults with Type 1 diabetes?

Author / Title / Reference / YrScottish Intercollegiate Guidelines Network. Lipids and the Primary Prevention of Coronary Heart Disease. 1–59. 2003.
N=15 studies, 9 relevant to type 1 diabetes (or diabetes type not specified)
Research DesignNational Clinical guideline
AimTo reduce incidence or coronary heart disease
PopulationCoronary disease population including a mixed diabetes population
InterventionLipid lowering agents (various)
ComparisonPlacebo
OutcomeIncidence of coronary disease and coronary events
CharacteristicsVaried between studies
ResultsEvidence from lipid lowering trials relevant to Type 1 diabetes
All evidence for trials of primary prevention of coronary heart disease with respect to lipid levels relates to type 2 diabetes
Secondary prevention trials of lipid reduction in diabetics or in populations which included a substantial diabetic subgroup have shown significant reduction in cardiovascular disease in both Type 1 and Type 2 diabetics.

In view of the observed association of dyslipiaemia with increased cardiovascular risk in diabetes, the positive benefit from lipid lowering among diabetic subjects included the secondary prevention studies, and the similar trend in favour of treating diabetes in the Helsinki Heart Study (Type 2 diabetes) and AFCAPS/TexCAPS (diabetes type not specified); it would seem prudent to recommend aggressive lifestyle modification to lose weight, reduce intake of saturated fat, increase consumption of fruit and vegetables, take regular exercise and where necessary introduce lipid lowering drug treatment for primary prevention in high risk diabetic subjects.

The higher absolute risk for cardiovascular disease in patients with diabetes suggests greater benefit from lipid lowering therapy than in non-diabetic subjects for a given cholesterol/HDL ratio. This is reflected in the currently available risk assessment methods, which appear to be appropriate for Type 2 diabetics without overt CHD unless there are signs on nephropathy (detectable urinary albumin excretion) in which case the risk is likely to be underestimated.

A Tayside study has raised concern about underestimating diabetic CHD risk, particularly in Type 1 individuals. These issues have been addressed by others and some possible solutions have been suggested
Hierarchy of Evidence GradingIa
CommentsDoes not differentiate in all cases between type 1 and type 2 diabetes, this is especially important when recommending the use of lipid lowering agents as complications of lipid abnormalities differ between the two types.
Evidence statements do not provide sufficient information to get a good grasp of the issues in lipid lowering in diabetes
Trials includedFrick et al (Helsinki Heart Study) 1987, Downs et al (results of the AFCAPS/TexCAPS trial) 1998, Koivisto et al (EURODIAB IDDM complications study group) 1996, Scottish Office Department of Health 1995, West of Scotland Coronary Prevention study group 1997, Keech (on behalf of the FIELD investigators) 1996, Holman (in publication), Steiner (The Diabetes Artherosclerosis Intervention study) 1996, Simes (Cholesterol Treatment Trials collaboratio) 1995, Sacks et al (Cholesterol and recurrent events trials investigators) 1996, Pyorala et al 1997, Lean et al 1990, Wiliamson et al 1995, Moy et al 1993, Turner et al (UKPDS) 1998, Yudkin & Chaturvedi 1999, Zambanini et al 1999, Haq et al 1996, Wood et al 1998
Reference / Citation181
Author / Title / Reference / YrRustemeijer, C., Schouten, J. A., Janssens, E. N. W., Spooren, P. F. M., & van Doormaal, J. J. 1997, “Pravastatin in diabetes associated hypercholesterolemia”, Acta Diabetologica, vol. 34, no. 4, pp. 294–300.
N=49 Patients with Type 1 or Type 2 diabetes and hypercholesterolaemia despite dietary intervention
Pravastatin: n=24, placebo: n=25
The Netherlands
Research DesignRandomised controlled trial
AimUse of statins to improve cholesterol levels
PopulationMixed diabetes population
InterventionPravastatin (20 mg at bedtime)
ComparisonPlacebo
OutcomeTotal cholesterol, HDL cholesterol, LDL cholesterol and triglyceride levels
CharacteristicsMean age (years): pravastatin=52, placebo=55; Sex (M/F): pravastatin=14/10, placebo=12/13; Diabetes (Type 1/Type 2): pravastain=11/13, placebo=11/14; number of concomitant medications: pravastatin=33, placebo=30
ResultsLipid parameters
Pravastatin vs. placebo
There were no differences between baseline parameters between the treatment and control groups.
At all visits pravastatin significantly reduced total cholesterol and LDL cholesterol compared to placebo (p<0.001)
At 16 and 24 weeks mean HDL cholesterol levels were significantly different between the treatment groups (p<0.01)
Pravastatin significantly reduced triglycerides compared to placebo after 8 and 16 weeks (p<0.01 and p<0.001) although the difference at 24 weeks was not statistically significant.
Changes in lipid parameters after 24 weeks pravastatin: Total cholesterol decreased by 22.2%, LDL cholesterol decreased by 25.8%, HDL cholesterol increased by 1.8%, triglycerides decreased by 13.6%
Changes in lipid parameters after 24 weeks placebo: Total cholesterol decreased by 0.6%, LDL cholesterol decreased by 2.0%, HDL cholesterol decreased by 7.7%, triglycerides increased by 1.9%
Taking glucose levels at baseline and changes in glucose levels as covariables in ANOVA analysis of the effects on lipid values, significance was reached for pravastatin treatment of triglyceride levels (p=0.009). In multiple regression analysis triglyceride values on all visits were predicted by changes in glucose levels (r2=0.29, p=0.0002)
Differences between type of diabetes
No differences were seen in pravastatin induced changes in serum lipids and lipoproteins with respect to diabetes type, except for total cholesterol at week 8 (p<0.05)
After 24 weeks total cholesterol was decreased by 24.0% in the type 1 diabetes group and 20.6% in the type 2 diabetes group.
For LDL cholesterol these figures were 29.1 vs. 22.8%, for triglycerides: 21.8 and 6% and HDL cholesterol increased by 5.5% and decreased by 1.7% in people with type 1 and type 2 respectively.
Clinical safety
No differences were found between the pravastatin and placebo groups for fasting glucose, HvA1c, serum creatinine and microalbuminuria at baseline or after 24 weeks of treatment.
No significant changes were found in haematological and biochemical parameters throughout the study
Mean values of blood pressure and body weight remained stable in the different groups during the study
Compliance measured by counting tablets at each visit was overall >80% in both groups. Pravastatin was generally well tolerated.
Two serious adverse events were noted (pravastatin=1 libido loss, placebo=1 muscle pain). Both patients dropped out of the study.
Hierarchy of Evidence GradingIb
CommentsFollow-up = 24 weeks
Study included dietary lead-in of ≥6 weeks
Dietician instructed patients to use a low-fat, low-cholesterol diabetic diet with appropriate caloric intake to maintain a stable body weight in the dietary lead-in period.
Dietary compliance was checked by a dietetian by means of a 2-day food record at every visit during the study.
Eligibility based on the mean of two measurements of total cholesterol in the dietary lead-in.
Baseline clinical safety assessments included patients history, complete physical examination, 12-lead electrocardiogram and routine clinical laboratory tests taking during the dietary lead in period.
Patients returned to the outpatient clinic at week −2, −1, 8, 16 and 24 weeks for interview of possible adverse reactions, interim illnesses, use of non-study drugs, adherence to diet and medication compliance (assessed by counting returned tables)
Blood samples were analysed for total cholesterol (TC), HDL cholesterol and triglycerides (TG) at weeks −1, 8, 16 and 14.
All lipid, metabolic control and laboratory safety measurements were conducted in the central same laboratory.
Total cholesterol and HDL cholesterol concentrations were measured using methods in accordance with the protocol of the Centres for Disease and Control/NHBLI Lipid Standardisation Program. Triglycerides were quantitated on the CHEM-1 analyser enzymatically.
Lipid values were withheld from patients and investigators during the study.
Safety parameters including haemoglobin were performed using standard techniques
Diabetic control was monitored by evaluating fasting glucose at each visit. HbA1c levels were measured at weeks −1, 8, 16 and 24.
Continuous variables were compared using t tests, discrete variables using chi-squared tests.
Mean percentual change form baseline in the lipid profile was compared at each time point across treatment groups using t- testing
Interactions of treatment with patients characteristics, including diabetes type were tested by ANOVA on differential treatment effects
Formal comparisons on tolerance and safety between placebo and pravastatin groups were carried out using chi-squared test.
No power analysis is included in the study. Study sample is small, especially as subgroup analysis are performed according to type of diabetes
No details are given of the randomisation, concealment of randomisation or blinding procedures.
Authors state that details of concomitant medication were collected from each patient, although details are not included in the analysis.
Two patients are reported as dropping out of the study, although only the patient in the pravastatin group is still included in the analysis
Reference/Citation182
Author/Title/Reference/YrRaskin, P., Ganda, O. P., Schwartz, S., Willard, D., Rosenstock, J., Lodewick, P. A., Cressman, M. D., Phillipson, B., Weiner, B., McGovern, M. E., Norton, J. M., Cucinotta, G. G., & Behounek, B. D. 1995, “Efficacy and safety of pravastatin in the treatment of patients with type I or type II diabetes mellitus and hypercholesterolemia”, American Journal of Medicine, vol. 99, no. 4, pp. 362–369
N=94 patient with type 1 or type 2 diabetes with hypercholesterolaemia despite dietary intervention
pravastatin: n=62, placebo: n=31
USA
Research DesignRandomised controlled trial
AimA study of the efficacy of a statin to improve blood cholesterol concentrations
PopulationMixed diabetes population
InterventionPravastatin (20 mg)
Comparisonplacebo
OutcomePrimary end points: Reductions in LDL cholesterol and triglyceride concentrations after 16 weeks of treatment
Secondary end points: changes in total cholesterol, VLDL cholesterol and HDL cholesterol concentrations at 16 weeks
CharacteristicsMean age (years): pravastatin=53.9, placebo=54.9; Sex (M/F): pravastatin=30/32, placebo=14/17; Diabetes (Type 1/Type 2): pravastain=20/42, placebo=10/21
ResultsLipid and lipoprotein response
Average daily dose of pravastatin at 16 weeks=29.5 mg. 47%(26/55) of patients had dose doubled at 8 week evaluation Statistically significant decreases in LDL cholesterol and VLDL cholesterol were seen at 8 and 16 weeks in the pravastatin group
(p≤0.001 for LDL cholesterol vs. placebo, p≤0.01 for VLDL cholesterol vs. placebo)
Reductions in calculated LDL and estimated VLDL cholesterol were 29.8% and 12.6% respectively (both p ≤0.001 vs. placebo)
Significant reductions in total cholesterol and triglycerides were seen after 23 weeks and at all remaining time points (except week 4 for triglycerides) for 16 weeks:
(p≤0.001 total cholesterol and p≤0.01 triglycerides vs. placebo)
HDL cholesterol levels were significantly increased in the pravastatin group at 8 and 16 weeks (p ≤0.05 compared with placebo)
At week 16 pravastatin reduced total cholesterol:HDL cholesterol from 6.2 to 4.5 and LDL cholesterol:HDL cholesterol from 4.5 to 3.0 (p≤0.001) compared with placebo for both ratios)
Analysis of type 1 and type 2 subgroups showed very similar reductions in LDL cholesterol and total cholesterol levels and increased in HDL cholesterol levels. Patients with type 2 diabetes had slightly greater reductions in triglyceride levels.

Safety
Pravastatin was well tolerated, with similar incidences of adverse events in both groups
One sudden death, attributed to possible cardiovascular cause occurred in the pravastatin group.
There were no discontinuations of study medication due to side effects
No significant differences were seen between treatment groups in the frequency of clinically significant laboratory test abnormalities including fasting blood glucose concentrations and HbA1c
Hierarchy of Evidence GradingIb
CommentsDietary stabilisation/placebo lead-in of 4 to 8 weeks, followed by a 24 week treatment period.
With counselling by a dietician, each patient was prescribed an American Diabetes Association diet: a low-fat, low-cholesterol diabetic diet with appropriate caloric intake to maintain a stable body weight.
Dietary prescription was given ≥4 weeks before blood was drawn for eligibly calculations based on lipid profiles were made and was to be followed throughout the trial. Dietary compliance was checked by means of a 3 day food record at periodic intervals.
Patients were asked not to make any other significant lifestyle changes
Lipid lowering medications were withdrawn ≥8 weeks before randomisation.
Patients who were already following a stable ADA diet or its equivalent, and were not taking any prohibited medications could enter the study at the beginning of the 4 week placebo lead in period.
Two blood samples for lipid analysis were drawn after fasts of ≥12 hours during the lead-in period 1 and two weeks before randomisation.
Two patients were randomly assigned to pravastatin for each assigned to placebo.
At 10 weeks pravastatin could be increased to 40 mg/day in patients who demonstrated persistent hypercholesterolaemia or decreased to 10 mg day in patients with LDL cholesterol <110 mg/dl after 8 weeks of treatment.
Cholestyramine or colestipol could be added after 18 weeks, based on lipid levels after 16 weeks if LDL cholesterol remained elevated.
Ratios of total cholesterol:HDL cholesterol and LDL cholesterol:HDL cholesterol were also calculated and analysed
Baseline clinical safety assessments included patients history, complete physical examination, 12-lead electrocardiogram and routine clinical laboratory tests taking during the dietary lead in period.
Patients returned to the clinic at 2 week intervals for the first 4 weeks and at 4 week intervals during the rest of the study
At each visit patients were interviewed for possible adverse reactions, interim illnesses, use of non-study drugs, adherence to diet and medication compliance (assessed by counting returned tables)
Analysis of lipid efficacy variables was performed by a central laboratory, in accordance with the Centres for Disease and Control/NHBLI Lipid Standardisation Program. All other laboratory tests were performed centrally and employed a quality assurance procedure.
Reference/Citation183
Author/Title/Reference/YrGoldberg, R. B., Mellies, M. J., Sacks, F. M., Moye, L. A., Howard, B. V., Howard, W. J., Davis, B. R., Cole, T. G., Pfeffer, M. A., & Braunwald, E. 1998, “Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators”, Circulation, vol. 98, pp. 2513–2519.
N=4159 patients (pravastatin=2081, placebo=2078)
Research DesignRandomised controlled trial
AimTo evaluate the effect of statin therapy in to minimize cardiovascular events
PopulationDiabetes group: n=586 (14.1 % of total study population)
InterventionPravastatin (40 mg/day)
Comparisonplacebo
OutcomePrimary outcome: combination of death from CHD plus nonfatal MI
Secondary outcome: bypass surgery or angioplasty
Characteristicsmen and postmenopausal women 21–75 years who had suffered MI between 3 and 20 months before randomisation, with plasma total cholesterol <240 mg/dL, LDL cholesterol 115–174 mg/dl and triglycerides <350 mg/dl
ResultsTreatment effect
Pravastain had similar effects on plasma lipid concentrations in the diabetes and nondiabetes groups
Compared with placebo, pravastatin reduced total cholesterol and LDL cholesterol by 19% and 27% in group with diabetes, compared to 20% and 28% respectively in those without.
Average on-treatment total cholesterol and LDL cholesterol values in the diabetes group were 170±33 and 96±21 mg/dl compared with 171±23 and 99±19 mg/dl in the nondiabetes group
Compared with placebo, pravastatin caused a 13% decrease in triglycerides and a 4% increase in HDL levels in people with diabetes.
Pravastatin treatment in the diabetes group was associated with 25% reduction of risk of coronary events (CHD death, nonfatal MI, CABG and PTCA) (p=0.05), similarly to those without diabetes. Adjustment for age and sex did not alter the magnitude of this effect
Pravastatin was also associated with a 13% reduction in the relative risk of primary end-point events (p=NS), compared to 28% (p=0.004) in the nondiabetes group. This is largely due to an absence of a reduction in the rate of CHD death in the diabetes group.
Because of their higher coronary event rate, diabetic patients had more benefit, expressed in absolute terms, than nondiabetic patients, an 8.1% absolute reduction of the secondary end points compare with 5.2% in the non diabetic patients.
Hierarchy of Evidence GradingIb
CommentsPatients entered into a dietary programme supervised by a dietician using the approach of the National Cholesterol Education Program
Plasma lipids withdrawn after an overnight fast were measured 2 to 3 times at baseline at intervals thereafter at a central laboratory certified for lipid measurements by the Centres for Disease Control.
Average duration of follow-up ~5 years
Patients were interviewed and asked whether they previously had been informed that they had diabetes or had received medication for diabetes
Subgroup analysis of previously recorded results
Full details of study protocol not included here. No details of whether a power analysis was employed
Presence of diabetes is patient reported
No differentiation made for type of diabetes, Only 18.6% of those in the diabetes subgroup were treated with insulin
The majority of patients (45.4%) were receiving sulfonylurea treatment.
All analysis were performed on an intention-to-treat basis
Reference/Citation184
Author/Title/Reference/YrSartor, G., Katzman, P., Eizyk, E., Kalen, J., Nilsson, A., Ugander, L., & Ursing, D. 1995, “Simvastatin treatment of hypercholesterolemia in patients with insulin dependent diabetes mellitus”, International Journal of Clinical Pharmacology & Therapeutics, vol. 33, no. 1, pp. 3–6.
N=25 patients had sufficiently low C-peptide levels to be truly insulin dependent and were included in the analysis simvastatin: n=12, placebo: n=13
Sweden
Research DesignRandomised controlled trial
AimTo assess the effect of statin therapy to improve cholesterol levels
PopulationType 1 diabetes population (Male)
InterventionSimvastatin 10 to 20 mg per day orally
ComparisonPlacebo
OutcomeTotal cholesterol, LDL cholesterol, HDL cholesterol and triglycerides.
HbA1c and fasting blood glucose
Characteristicsmen (20–65 years) with a five year history of insulin treated diabetes mellitus and fasting total serum cholesterol ≥6 mmol/l prescribed a cholesterol lowering diet.
ResultsSimvastatin 10–20 mg daily significantly decreased total serum cholesterol and LDL cholesterol concentration (p<0.001 in both after 4 and 16 weeks). No significant difference was seen with placebo.
Reduction in total cholesterol and reduction in LDL cholesterol were closely related (R=0.92, p<0.001)
HDL cholesterol and triglycerides were unchanged following simvastatin treatment compared to placebo.
The ratio between LDL and HDL cholesterol was reduced from 4.1±1.7 to 2.0±0.6 with simvastatin and from 3.5±1.1 to 3.2±1.4 with placebo (between groups p=0.011)
Body weight was unchanged after either intervention as was BP and heart rate.
Simvastatin had no significant effect on fasting blood glucose or HbA1c. Similar insulin doses were used in the simvastatin and placebo group throughout the study.
Serum electrolytes, rate, creatinine, liver enzymes, creatinine kinase and serum TSH did not differ between the treatment groups
Ophthalmological slitlamp examination before and at the end of the study did not show development of new lenticular opacities
Hierarchy of Evidence GradingIa
CommentsGlucagon stimulation tests performed to test true insulin dependency.
Following four weeks treatment, both placebo and simvastatin dose was increased to two tablets daily during the following 12 weeks if serum cholesterol was >3.6 mmol/l.
Fasting HDL-cholesterol, LDL-cholesterol, triglycerides, alkaline transferase, bilirubin, sodium, potassium, creatinine, urate creatinine kinase, blood glucose and HbA2c were determined ≥ 10 weeks before inclusion, at randomisation and after 4 and 16 weeks of treatment.
All laboratory analyses were performed at the departments of clinical chemistry at the hospital where the patient was enlisted.
Concomitant medication reported in five patients, but only discontinued in one patient
Statistical evaluation was performed using student’s unpaired t test and fisher’s exact test.
Correlation coefficients were calculated using linear regression analysis. Significance was at 5%
Glucagon stimulation test was employed to ensure all patients were IDDM
Pre-treatment HDL cholesterol levels were considered relatively high, which authors state explains the lack of increase in HDL cholesterol following simvastatin treatment
Reference/Citation185
Author/Title/Reference/YrHommel, E., Andersen, P., Gall, M.-A., Nielsen, F., Jensen, B., Rossing, P., Dyerberg, J., & Parving, H.-H. 1992, “Plasma lipoproteins and renal function during simvastatin treatment in diabetic nephropathy”, Diabetologia, vol. 35, no. 5, pp. 447–451.
N=26 People with Type 1 diabetes and persistent albuminuria (>300 mg/24 h)
simvastatin: n=14, placebo: n=12
Denmark
Research DesignRandomised controlled trial
AimTo assess the effect of statin therapy to improve cholesterol levels
PopulationMixed diabetes population
InterventionSimvastatin 10 mg per day orally
ComparisonPlacebo
OutcomeTotal cholesterol, LDL cholesterol, apolipoprotein A and apolipoprotein B, UAE and glomerular filtration rate
CharacteristicsDiabetic nephropathy according to established criteria, total cholesterol ≥5.5 mmol/l, age 18–50 years, serum creatinine ≤200 μmol/l
ResultsPlasma concentrations of total cholesterol, LDL cholesterol and apolipoprotein B were significantly reduced in the simvastatin-treated group during 12 weeks treatment (p<0.01). No changes were observed in the placebo treated group.
Significant differences in mean changes from baseline to 12 weeks were observed after simvastatin treatment compared to placebo in:
Total cholesterol (mmol/l): –1.58±0.25 vs. 0.078±0.25, LDL cholesterol (mmol/l) –1.67±0.21 vs. 0.013±0.21, apolipoprotein B (g/l) –0.31±0.67 vs. 0.06±0.05
HDL cholesterol and apolipoprotein A were unchanged in both groups.
Urinary albumin excretion, glomerular filtration rate, and arterial blood pressure were comparable between the simvastatin- treated group and placebo as were HbA1c and blood glucose, after 12 weeks of treatment.
Plasma concentrations of alkaline phosphatase, creatinine kinase, aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, haemoglobin, differential counts, platelets, sodium, potassium and creatinine were comparable between the groups.
Hierarchy of Evidence GradingIb
CommentsAll included patients were insulin-dependent from time of diagnosis and receiving ≥2 daily injections of insulin.
All patients received their usual antihypertensive treatment during the study period and doses were unchanged. No patients were taking any other drugs.
All patients were given dietary advice for a diet of 50% carbohydrate, 15% protein and 35% fat with no sodium restriction.
Total cholesterol was re-measured 3 weeks later and all 26 patients still had total cholesterol >5.5 mmol/l and no changes in glycaemic control or body weight.
Simvastatin dose was increased to 20 mg (two tablets) and placebo to two tablets if total cholesterol remained over 5.5 mmol/l after 6 weeks of dose titration.
Venous blood samples were collected after an overnight fast. Total cholesterol was measured enzynmatically, LDL cholesterol calculated using Friedewald’ s formula.
Reference/Citation186
Author/Title/Reference/YrWinocour, P. H., Durrington, P. N., Bhatnagar, D., Ishola, M., Arrol, S., Lalor, B. C., & Anderson, D. C. 1990, “Double-blind placebo-controlled study of the effects of bezafibrate on blood lipids, lipoproteins, and fibrinogen in hyperlipidaemic type 1 diabetes mellitus”, Diabetic Medicine., vol. 7, no. 8, pp. 736–743.
N=36 patients were randomised to active treatment or placebo at the end of the run-in period.
Bezafibrate: n=17, placebo: n=19
UK
Research DesignRandomised controlled trial
AimTo evaluate the use of a lipid modifier to improve cholesterol levels
PopulationType 1 diabetes
InterventionBezafibrate (400 mg once daily before the evening meal)
ComparisonPlacebo
OutcomeTotal serum cholesterol, total serum triglycerides, LDL cholesterol, HDL cholesterol, VLDL cholesterol, fasting blood glucose, HbA1c, Fibrinogen, apolipoprotein (a) and B, and serum alkaline phosphatase
CharacteristicsMale: bezafibrate=11, placebo=12; age (year): bezafibrate=53.7 (37–64), placebo=49.1 (17–64), duration of diabetes (year): bezafibrate=18.2 (5–45), placebo=15.7(3–36)
ResultsFollowing bezafibrate therapy, no changes in insulin dosage, BMI, HbA1c, serum transaminases or markers of renal function were recorded and measurements were comparable to the placebo group.
Alkaline phosphatase activity fell significantly in bezafibrate treated patients significantly more than those in the placebo group at 1, 2 and 3 months.
Fasting blood glucose levels decreased significantly from 8.5 (1.1) mmol/l at end of run in to 6.40 (0.7) mmol/l (p<0.05) following three months bezafibrate therapy.
Levels were not comparable between the two treatment groups at the end of the run-in period, but this difference greater and statistically significant at 3 months (p<0.001).
Total serum cholesterol and total serum triglycerides were decreased throughout the treatment period, and were significantly lower than those in the placebo group.
Levels were not comparable at the end of the run-in period but only became significantly lower than in the placebo group after 1, 2, and 3 months of active treatment.
VLDL cholesterol concentrations were lower in the bezafibrate group compared to placebo at 1 and 3 moths.
LDL cholesterol values were significantly decreased by bezafibrate in comparison with levels at the end of the run-in period but not significantly different to those seen after treatment with placebo
Serum apolipoprotein A and B did not differ following treatment with bezafibrate or placebo.
Fibrinogen levels declined progressively with bezafibrate over 3 months of treatment. Concentrations were initially higher in the bezafibrate group after run-in but were reduced to less than those of placebo following active treatment.
Hierarchy of Evidence GradingIb
CommentsTreatment groups differed significantly at treatment initiation (following run-in period)
All patients received standard dietary advice (isocaloric diet with fixed amount of carbohydrate and calories derived from 50% carbohydrate, 30% fat and 20% protein)
All patients whose fasting cholesterol and/or triglyceride levels remained >5.5 mmol/l or 2.00 mmol/l respectively after a 4 week run-in period on placebo were randomised to bezafibrate or placebo for a further three months.
Fasting blood tests to assess efficacy and safety were performed once monthly.
Compliance was assessed by tablet counts, by confirming reductions in circulating serum alkaline phosphatase and detection of bezafibrate concentrations in fasting serum at the end of the 4 month study period.
Side effects were assessed by direct enquiry
All lipid and lipoprotein estimations were carried out in duplicate. Fasting serum cholesterol and triglyceride concentrations were measured enzymatically.
Assays were performed at the local laboratory, which participates in the UK external quality assurance scheme for cholesterol estimation.
Results from patients who completed the study were analysed
Reference/Citation187

From: Appendix D, Evidence tables

Cover of Type 1 Diabetes in Adults
Type 1 Diabetes in Adults: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care.
NICE Clinical Guidelines, No. 15.1.
National Collaborating Centre for Chronic Conditions (UK).
Copyright © 2004, Royal College of Physicians of London.

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