Abstracts/Atherosclerosis
I12 (1995) 261-267
Improved glycaemic control and insulin sensitivity during sustained suppression of serum non-esterified fatty acids (NEFA) in type 2 diabetic patients
CHANGES IN SERUM LIPIDS, LIPOPROIEINS, AND CHOLESTEROL ESTERIFICATION (LCAT) ACTIVITY CHOLESTERYI. ESTER TRANSFER (CET) DURING WEIGHT REDUCTIONIN OBESESUBJECTS
Kumar S, Durrington PN, Mackness MI, Bhatnagar D, Gordon C, Boulton AJM
D Bhatnagar,C Web&we*. G Wood. T LavaI*, PN Dnnington. University Dept of Medicine, Royal Infirmary , Manchester& University Dept of Clinical Biochemistq*. HopeHospital. Salford
Manchester Royal Infirmary, hlanchester, UK The eff’ect of sustained suppression of NEFA was studied in 49 hypertriglyceridaemic (> 2.2 mmoli) type 2 diabetic patients, randomised to receive either sustained-release acipimox (acipimox SR, n=33) or placebo (n=16) for 8 weeks. Fasting semm lipids and glucose were measured in all subjects In 36 patients, glucose tolerance was assessed using a I hour intravenous glucose infusion test and insulin sensitivity was derived by mathematical modelling During acipimox treatment. there were decreases in fasting glucose (11.2 2 0 6 vs 10 6 i 0 6 mmol/l, p
LOW-DENSITYLIPOPROTEINCHOLESTEROL ESTERIFICATIONAND ITS RELATIONSHIP WITH LDL TURNOVER IN DIABETES. P Deegan. D Owens, P Collins, A Johnson and GH Tomkin. Trinity College,The Adelaide Hospital and The Royal College of Surgeonsin Ireland,Dublin, Ireland. We have previously shown that increasedlow-density lipoprotein (LDL) esterified to free cholesterol (WF) ratio, which occors in diabetes,is associatedwith impairmentof the ability of LDL Lo downregulatecellular cholesterolsynthesisin vitro. We have also shownan associationbetweenE/F ratio andLDL cholesterollevels. Thus we setout to investigatein viva the relationshipbetweenE/F ratio andLDL turnoverin non-insulin-dependent diab&es(NIDDhQ. Eleven hypercholesterolaemic (HC) NIDDM patients,mean cholesterol7&0.8 andten normocholesterol~mic (NC) NIDDM patients, mean cholesterol 5.421.1 were studied. LDL (d 1.019-1.063)was isolated by density gradientultracentrifngation, iodinated and re-injected into the patient. LDL turnover was determinedby measwingclearanceof (l%)LDL from plasmaover a ten day period. Fractional catabolicrate (FCR) was determined usinga two-pool model.In theNC groupFCR correlatednegatively with total cholesterol(1=.856,pc.002)andBMI (x81, p<.OO5).In the HC group FCR correlatedpositively with cholesterol(lr.725, 1x012), HbAlc (x93, p<.OOl),triglycerides(r=.81, p<.OO2)and E/F ratio (~83, p<.OO2).In the HC group E/F ratio correlated with triglycerides (~87, p< ,001). The assocationbetween E/F ratio and faster LDL clearancein hypercholesterolaemicdiabetics suggeststhatnon-receptor-mediated uptakeof thisalterredLDL was illcmwd
We have examined the effect of a very low calorie diet (500 k&day) on plasmalipoproteinsand reverse cholesteroltransport in 22 subjects(6M, 16F) with moderateobesity (BMI 35Si3 6 kg/m*) referedto the ObesityClinic. Week1 Baseline Week 1 4 Ml.6 * 5.5i1.5 TC (mmol/l) 6 4*1.4 1.41(0eoTG (mmol/l) 1 96(0.401.33(0.6X2 23) 4 70) 2.52)** 3.1i0.6 * LDL (mmoV1) 4 6+1 2 J.li1.4 0.Y210.22* HDL (mmolll) I, 15+025 1.0sioo.25 0 29 0 59 VLDL 0.27 (0 09-o 52) (mmol/I) (0.0X-1.56) (0.06-0.61) 46 0+15.5 LCAT 752+1X8 51.1+134 ** (nmoI/mlih) Xl CET 173 X.9 (nmol/ml/h) (2.0-35.6) (2-14.7) (2.X-315) ** Weight (kg) 112.9+25.2 108.7123.8** 104.X*23.1* * significantdifferencebetween week l&4 , but not week 0 & I ** significantdifferencebetween baseline& week I In the first week, when weight loss is dueto wbohydrate & water loss, there is a predominant decrease in triglyceride-rich lipoproteins & LCAT & CET activity. After week 1 when fat mobilisation is established,mainly TC, LDL & HDL arc decreased.
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