Lipids I

POS-001-152 ACUTE LIPID TOLERANCE TEST, IS IT OF ANY SIGNIFICANCE ?

B. KARAMANOS, J. SAFLIANIS, Ch. TOUNTAS, D. ROUSSI-PENESSI, A. CHRYSANTHIS and Th. KARDOYIANNIS.

Diabet ic Center, Athens Univers i ty , Hippokration Hospi ta l , Athens, Greece.

In order to invest igate the acute ef fects of an oral fa t and cholesterol load on blood l i p i d s we studied 59 non-diabetics and 19 Type I I d iabet ics , wi th the L ip id Tolerance Test, consist ing in the adminis t rat ion of a meal with 50 g fa t and I000 mq Cholesterol and measurement of the serum l i p i ds before and 4 hours a f te r i t . A Cholesterol increase 4h>20% of the fast ing value characterizes the "responders"(Posi t ive Test). Among the non-d iabet ics, 25 (42.4%) were "responders", who comnared to "non-responders" had not d i f f e ren t fast ing values of glucose (80.8±2.5 vs. 87.3±3.3 mg% p > . 0 5 ) , Cholesterol (241.1±15.5 vs. 269.4±14.3 mq% p >.05) , TG (181.7t27.2 vs. 167.4±21.2 mg% p • . 0 5 ) , HDL (60.8±4.6 vs. 55.5±3.3 mg% p >.05) , LDL (145.5±14.1 vs. 183.8±12.7 mg% p • . 0 5 ) and insu l in (9.1±.8 vs. 10.1±1.1 uu/ml p> .05) whi le they had lower C-~eptide (1.04±.1 vs. 1.4±. i nq/ml p < . 0 5 ) . LDL increased in "responders" (145.5±14.1 vs. 222.1 ±17.8 p<.O01) but decreased in "non-responders"(183.8±12.7 vs. 140.9±15.4 p <.001), whi le TG and HDL increased in both ( p < . O l ) . Only 3 d iabet ics were "responders'~ (15.8%). Diabetics compared to non-diabetics had higher fast ing Chol and TG (257.4±16.3 vs. 327.5±24.3 and 173.3± 23.8 vs. 317.7±67.2 respect ive ly p <.01) which might explain the low prevalence of "responders". Conclusions: a) A pos i t i ve l i p i d tolerance test d i f f e ren t i a t es a group of normal subjects (42.4%) wi th abnormal cholesterol and LDL increase which cannot be predicted by the fast ing l i p i d levels and might indicate pred ispos i t ion for hypercholesterolaemia, b) Type I I d iabet ics show low prevalence of pos i t i ve tests probably because most of them are already hypercholesterolaemic.

POS-001-153 ORIGIN AND DEVELOPMENT OF HYPERTRIGLYCERIDEMIA IN VENTROMEDIAL

HYPOTHALAMIC LESIONED RATS

S.SATOH, S.INOUE, T.MURASE, Y.TAKAMURA The Third Depar tment of Internal Medicine, Yokohama City University, Yokohama, Japan

Ventromedial hypothalamic (VMH) lesioned rats have hypertriglyceridemia after establishment of obesity. The present study investigated when hypertriglyeeridemia occurs in these rats and what mechanism exists it. Serum triglyceride and it 's lipoprotein fraction before and at 1,2,3,4,6,8,12 weeks af ter VMH lesions in rats. Hepatic triglyceride secret ion rate using Triton WR 1339 (Robertson et al) were deter - mined for est imating triglyceride production in the serum and postheparin lipoprotein lipase (LPL) using radioisotope method (Murase and Uchimura) were determined for triglyceride uptake in adipose tissue at 1 week and 12 weeks af ter VMH lesions. Lipoprotein analysis was done by High Performance Liquid Chromatography (Hara et al). Body weight and serum insulin of VMH lesioned rats continued to increase more than those of control rats. Af ter 4 weeks, serum triglyceride of VMH lesioned rats became higher than that of control rats. Analysis of lipoprotein revealed that chylomicron and VLDL fractions increased in VMH lesioned rats. Hepatic triglyceride secretion increased VMH lesioned rats at 1 and 12 weeks. LPL activity of VMH lesioned rats is higher than that of control rats. These results suggested that hyper- triglyceridemia of VMH lesioned rats results from both increased endogenous hepatic triglyceride production and exogenous dietary intake when capacity of triglyceride uptake by adipose tissue becomes restr ic ted due to increased accumulation of fat deposit in adipose tissue.

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POS-001-154 EFFECT OF el-BLOCKER, BUNAZOSIN, ON SERUM GLUCOSE AND LIPIDS METABOLISM

S. INOUE, T. FUJII, K. NUMATA, K. TANAKA, H. NAGASE, M. NAITOH, H. SUZUKI, Y: TAKAMURA The 3rd Department of Internal Medicine,Yokohama City University,Yokohama,Japan

Hypertention is often associated with diabetes mellitus. In the treatment of hypertention in diabetic patients, we have some difficulties in selecting anti- hypertensive agents since many agents may affect blood suger and serum lipids. It is reported that el-blocker improved serum lipids in human. The present study was designed to investigate whether ~l-blocker, bunazosin may affect blood sugar and serum lipids in normal and streptozotocin (40mg/kg)-induced diabetic rats. After 6 weeks treatment of bunazosin (3% bunazosin in powder diet), glucose tolerance test (0.5g/kg,iv) and overnight fasting serum lipids determinations with lipoprotein analysis by High Performance Liquid Chromato- graphy (HPLC) by the method of Hara et al were performed. Bunazosin gave no effects on body weight, glucose tolerance, insulin secretion, serum cholesterol, triglyceride, phospholipid, free fatty acids and lipoprotein fractions in normal and diabetic rats. In conclusion, bunazosin has an advantage as an anti- hypertensive agent in the treatment of hypertension in diabetics.

POS-001-155 EXACERBATION OF INSULIN RESISTANCE AND LIVER LIPID ACCUMULATION BY FRUCTOSE FEEDING

H.SUZUKI, S.SATOH, T.SAITOH, M,NAITOH, S.INOUE and Y.TAKAMURA The Third Department of Internal Medicine, Yokohama City University Yokohama Japan

The present study investigated the effects of high carbohydrate diet on glucose and lipid metabolism in rats with hyperinsulinemia and hypoinsulinemia. Rats with hyperinsulinemia were made by ventromedial hypothalamic lesions (VMH), and rats with hypoinsulinemia were made by streptozotocin injection (35mg/kg) (STZ). Both rats were fed on a high fructose diet or a high glucose diet for ten weeks and several parameters were examined. By feeding fructose diet, VMH rats showed no change of parametrial fat pad and body weight, increase in liver lipid, no change of serum triglyceride(TG), and worsening glucose tolerance with increase in insulin secretion. STZ rats showed decrease in body weight, no change of parametrial fat pad, no change of liver lipid, increase in serum TG, and worsening glucose tolerance with increase in insulin secretion. By feeding glucose diet, VMH rats showed decrease in body weight and parametrial fat pad, no change of serum TG, and improving glucose tolerance with decrease in insulin secretion. STZ rats showed no change of every parameter.

The results suggested that fructose diet worsens glucose tolerance by increasing insulin resistance both in VMH and STZ rats, on the other hand, glucose diet improves glucose tolerance by decreasing insulin resistance. Fructose diet accelerates liver lipid accumulation when there is a hyperinsulinemia.

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POS-001-156 ALTERED LIPID AND CARBOHYDRATE METABOLISM IN NON-INSULIN DEPENDENT DIABETES MELLITUS (NIDDM).

R PASMANTIER, R CHAIKEN, A PSIMOULIS, S EIRSCH, V BROWN, BE LEBOVITZ Department of Medicine, State University of New York, Health Science Center at Brooklyn

Brooklyn, New York. U.S.A.

we assessed what effect changes in plasma glucose (PG) and indices of insulin action would

have on lipoprotein profiles in NIDDM. We studied 15 patients with poor glucose control on maximal sulfonylurea (S) - glipizide 20mg bid-(6 men, 9 women; age 51+/-2 yr; FPG 257+/

-14/mg/dl; BMI 30+/-ikg/m2) with initial 24 hr PG and insulin profiles, HBAIC, hepatic glu-

cose production (BGP), peripheral insulin sensitivity (M) using the insulin clamp technique

and lipoprotein profiles. One third remained on S, 1/3 received human proinsulin (HPI) and

1/3 HPI with S. Patients were seen monthly for FPG, HBAIC and lipoproteins. Initial studies showed a correlation (r=-.54) between M and triglycerides (TG). NO correlation was found between M and HDL, nor between HGP and TG or HDL. After 2 months of an intensive glucose

regulation program there was a correlation between change in FPG and TG (r=.82). 10/15 with

improved glycemia had a 31% drop in TG, no change in HDL or body weight.

n-10 FPG (mg/dl) HBAIC(%) TG(mg/dl) HDL)mg/dl) before 266+/-17 9.1+/-.5 103+/-12 54+/-6 after 149+/-22 7.3+/-.3 71+/-5 56+/-6 p= 0.01 0.01 0.003 NS

5/15 with no change in glycemia also showed no change in TG, HDL, or body weight. We conclude TG and HDL are independent of each other and BMI, FPG and insulin levels in poorly controlled NIDDM. These data suggest that VLDL and HDL metabolism are independ-

ently related to carbohydrate metabolism and may partly explain the association of NIDDM,

decreased insulin action and altered lipoproteins.

POS-001-157 UREMIC HYPERTRIGLYCERIDEMIC PATIENTS WITH AND WITHOUT DIABETES MELLITUS:APOLIPO- PROTEIN C AND E ISOFORMS.

G. PAGANO, M. CASSADER, G. RUIU, R. GAMBINO, G. TRIOLO. Is t i tu to di Medicina Interna - Universit~ di Torino - Corse Polonia 14 - Torino ( I ta ly ) .

Triglyceride-rich lipoproteins are increased in uremic patients,both normal and diabetic. Apoli- poproteins C and E are involved in tr ig lyceride catabolism. We have evaluated Ape CII,CIII pl~ sma levels and Ape CIII,E isoforms in a group of 8 insulin-dependent diabetic(D) and 7 non-dia betic(ND) uremic patients in dialysis.Lipoprotein prof i le and apoproteins C and E were s tud i~ by preparative ultracentrifugation, radial immunodiffusion and isoelectrofocusing before and after neuroaminidase treatment. For the study were selected only hypertriglyceridemic patients (plasma triglycerides=Tg above 180mg/dl)and were all compared with hypertriglyceridemic(HTG)non- uremic patients.The 8 D and 7 ND showed not signif icat ive differences in total Tg(195~12 vs 204 +22mg/dl) and in VLDL-Tg(120+I8 vs 129+20mg/dl),also when compared with non-uremic patients. Ape CII levels were not signTficantly dif ferent between D and ND(3.5+0.8 vs 3.1~O.9mg/dl), but signif icantly different(p<O.Ol)when compared with HTG non-uremic patTents(8.3+l.7mg/dl). The differences of Ape CIII levels were not signif icantly different in al l groupsTl9.1+O.6 in D, 17.9+I.I in ND, 19.1+2.2mg/dl in non-uremic patients).Isoelectrofocusing on Ape cITI isoforms showed a signif icati~e increase in Ape CIII 2 in all uremics compared to HTG non-uremic patients (56.7% in D, 53.1% in ND vs 37.2~)and a signif icat ive increase of Ape CIII 1 in ND and HTG non- -uremic patients(30.2% in D vs 36.7% in ND and 50.7% in HTG non-uremic patlents).Apo E isoforms analysis showed an increase in sialated proteins in D and in ND compared to HTG non-uremic pa- tients(p<O.O5).Sialated Ape C and E are increased in uremics and may be involved in reduced Tg- rich lipoproteins catabolism .Diabetes mellitus doesn't seem to worsen this feature.

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POS-001-158 HMGCoA REDUCTASE INHIBITION WITH MK-733 IN HYPERCHOLESTEROLAEMIC DIABETICS

LA BACH, ME COOPER, RC O'BRIEN, A WIRTH, G JERUMS. Endocrine Unit, Austin Hospital, Heidelberg, Australia, 3084.

Hypercholesterolaemia and diabetes are both risk factors for atherosclerosis. Diabetes is associated with many abnormalities of lipoprotein metabolism. We studied the efficacy and tolerability of the HMGCoA reductase inhibitor, MK-733, in 20 hypereholesterolaemic diabetics. Patients with total cholesterol >6.7raM and duration of diabetes >12 months were enroUed. Six patients were treated with insulin and five were treated with oral hypoglycaemic agents.Two patients were on stable doses of B-blockers and three were on thiazides. After a lipid lowering diet for at least four weeks, subjects were randomised in a double blind manner to receive 20 mg MK-733 or placebo daily. If total cholesterol remained > 6.0 raM, the dose was doubled at 6 weeks. Data shown are for the first 11 patients. There were no baseline differences in weight (85.6 + 12.1 kg, mean + SD), HbA1 (10.2 + 1.8%), total cholesterol (7.6 :i: 0.9 raM), HDL cholesterol (1.0 + 0.2 raM), total/HDL ratio (8.0 + 2.2), triglycerides (3.8 + 2.5 raM) or Apoprotein B (111 + 4 mg/di). The following table shows percentage changes (mean + SEM),* 19<0.05, ** p < 0.005, MK-733 vs placebo:

Placebo (n = 4kweek 6 MK-733 (n = 7k week 6 MK-733 (n=6~. week 10 Total cholesterol 1.3 + 7.0 -22.0 + 2.7** -26.8 + 7.0* I-IDL cholesterol 0.0 + 4.5 13.9 + 5.3 21.3 + 4.8 Total/HDL cholesterol 2.6 :i: 10.1 -31.0 + 2.7** -38.9 + 7.3* Triglycerides 15.2 + 20.6 -13.4 :h 6.5 -4.0 + 17.8 Apoprotein B 5.3 5:5.5 -24.7 + 6.8** -22.2 + 5.3*

MK-733 reduced total cholesterol and Apoprotein B to a similar extent. Cholesterol subfraction (LDL, VLDL) and apoprotein AI &AII data were also measured There was no change in glycaemic control throughout the trial as evidenced by HbA1, fructosamine and fasting plasma glucose. Side effects included constipation in one patient and nausea in another. MK-733 is a safe and effective drug for the treatment of hypercholesterolaemia in diabetics.

POS-001-159 2HERE ARE SOME DIFFERENCIES IN LIPOPROTEINS AND APOPROTEINS LEVELS IN SERUM OF DIABETIC GIRLS AND BOYS ?

B JAMSKA, H DZIATKOWIAK*, M CIECHANOWSKA*, K DOLEZAL ~ bepartment of Clinical Chemistry and Clinic of Metabolic Diseases*,Kopernika 15 Clinic of Endocrynology, Institute of Pediatrics,Wielicka 265, Cracow,Poland

In this study we analysed the lipoproteins and apoproteins levels in diabeti girls and boys. The children were divided according to age: 21 girls (3-1U,y~ar old) and 15 boys (3-11 years old), 31 girls (10-19 years old) and 21 boys (14-1 years old). Triglycerides, total cholesterol were measured enzymatically (Boehringer Mannh) VLDL was isolated by ultracentrifugation at d=1.006 g/ml, HDL cholesterol was determined after heparin-manganese precipitation, LDL cholesterol was calcUl~te from Friedewald formula, apo AI was determined by radial immunodifusion, apo B by rocket immunoelectrophoresis. It was found that in younger group of children significantly higher level of triglycerides in serum and in VLDL fraction (with the higher level of choleste rol in VLDL) in boys compared with girls was noticed. In older group there was no significant differencies in lipoprotein and apoproteins levels between girls and boys except the significant lower level of HDL 3 cholesterol in boys. It is interesting to note that in this group of girls the higher level of HDL cholesterol (not significant) and the higher level of HDL3 cholesterol (p<0.05) than in boys was found. These data and especially the HDL-HDL 3 cholesterol increase in older girls will be discussed.

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POS-O01-160 INFLUENCE OF HUMAN PROINSULIN AND NPH INSULIN ON LIPOPROTEINPROFILES IN TYPE 2 DIABETIC PATIENTS

J.HUISMAN, D.W.ERKELENS. UNIVERSITY HOSPITAL UTRECHT, NETHERLANDS.

In 1985 we reported that during a 24 hours euglycemic glucose clamp proinsulin stimulates triacylglycerol production in the liver less then biosynthetic human insulin (Diabetes Re- search and Clinical Practice, 1985;suppl.l:253). In order to evaluate further risk factors for atherosclerosis in type 2 diabetes we compared lipoproteinprofiles in 12 C-Peptide posi- tive type 2 diabetic patients. 6 patients were treated for 12 weeks with human proinsulin (Pro), injected s.c. at 22.00 hours p.m. 6 patients were treated in the same way with NPH in- sulin (NPH). The aim was to reach fasting bloodglucoselevels under 8 mmol/l. A second injec- tion was added before breakfast if 16.00 hours bloodglucose was above i0 mmol/l. HbAI values (normal range 4-8.5%) before treatment were 10.2%+4.2 in the Pro group and 11.1%+4.3 in the NPH group (n.s) After treatment HbA1 was respectively 8.3%+3.2 and 9.6%~2.8 (p(O.O2).No sta- tistically significant differences were found in lipoprote~nprofiles in both groups ((i) be- fore Pro, (2) after Pro, (3) before NPH, (4) after NPH): apolipoprotein A, mg/dl: 126+18, (2) 162+21, (3) 163~34, (4)171~28; apolipoprotein B: (i) 84~24, (2) 76+13, (3) 82+16, (4) 76+11; cholesterol, mmol/l: (i) 5.7+1.5, (2) 5.3+0.58, (3) 5.7+1.08, (4) 5.4+0.81; V[DL chol:(l~ 1.27+1.01, (2) 0.68~0.38, (3T o.75+0.4, (~) 0.57+0.32; [DL chol: (i) 3.67~1.26, (2) 3.18~0.8, (3) 5.83+0.72, (4) 3.61+0.74; trig~ycerides, mmo~/l: (i) 1.15~0.74, (2) 1.63~1.39, (3) 1.33~ 0.54, (4T 1.12+0.45; VLDL trig: (i) 0.58~0.17, (2) i.ii~0.56, (3) 0.81~0.18, (4) 0.67~0.13; L+HDL trig: (IT 0.73~0.33, (2) 0.52~0.15, (3) 0.53+0.21, (4) 0.45~0.16. No differences were found in HDL cholesterol values before treatment. After Pro therewas a greater rise in HDL cholesterol than after NPH: (i) 1.02+0.23, (2) 1.15+0.23, (3) 1.15+0.34, (4) 1.22~0.31, p(O.03, In co~lusion: treatment with Pro compared to NPH resulted in lower--HbAl valuesin the Pro group. No differences were found in lipopr~teinprofilee, except for a higher rise in HDL cholesterol in the proinsulin treated group.

POS-O01-161 LIPOPROTEIN LIPASE IN SKELETAL MUSCLE IS RELATED TO INSULIN SENSITIVITY.

T POLLARE, H LITHELL, I SELINUS, B VESSBY Department of Ger ia t r i cs , Uppsala Univers i ty , Uppsala, Sweden.

The present invest igat ion was designed to evaluate in a cross-sect ional study the ef fects of obesity alone and in combination wi th hyperinsul inaemia, wi th or wi thout glucose in to lerance, on the peripheral insu l in s e n s i t i v i t y and l i popro te in l ipase a c t i v i t y (LPLA) in a we l l -de f ined male populat ion. Subjects: 45 men (x 63 years, range 56-67) were selected from a health survey, 28 of them met ~ o w i n g c r i t e r i a and could be a l located to one of four groups: I) BMI <27, normal fas t ing insu l in concentration and i v glucose to lerance; 2) BMI >27, normal fas t ing glucose and insu l in concentrations and i v glucose to lerance; 3) BMI >27, normal glucose to lerance, hyper insul inae- mia; 4) BMI >27, abnormal i v glucose tolerance and hyperinsul inaemia. Methods: Adipose and muscle t issue b iopsies, intravenous fa t tolerance tests (IVFTT), postheparin p as-laTm-a-lipolytic a c t i v i t i e s , IVGTT and insu l in s e n s i t i v i t y estimated by the euglycaemic insu l in clamp technique. Results:

insu l in concentrations (mU/l) 5.7 ± 3.4 7.3 ± 3.2 23.5 ± 3.4 19.8 ± 8.5 I v glucose tolerance (% min - I ) 1.7 ± 0.5 1.3 ± 0.5 1.3 ± 0.4 0.5 ± 0.2 Glucose disposal ( l as t 60 min) mg/kg/min 8.1 ± 2.1 6.0 ± 0.7 3.2 ± 0.5 1.9 ± 1.0 LPLA in muscle (mU/g) 46.1 ± 23.7 40.9 ± 25.9 22.8 ± 6.3 30.9 ± 12.8 S t r i g l yce r i des (mmol/l) 1.4 ± 0.6 2.1 ± 1.5 2.9 ± 1.2 3.0 ± 1.3 Muscle LPLA was pos i t i ve l y cor re la ted to insu l in s e n s i t i v i t y (p<O.01). In a stepwise regression model, 59% of the var ia t ion of skeletal muscle LPLA was explained by insu l in s e n s i t i v i t y , fas t ing plasma glucose, and plasma insu l in values at 90 min (during IVGTT). Conclusion: The low LPLA in skeleta l muscle and the low insu l in s e n s i t i v i t y might explain the im- paired glucose and l i p i d metabolism in glucose in to le ran t man.

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POS-001-162 LIPOPROTEINS AND APOPROTEINS IN SERUM OF DIABETIC CHILDREN AND OBESE CHILDREN

H DZIATKOWIAK, B JAMSKA*, M RYBAKOWA Clinic of Endocrynology, Institute of Pediatrics, Wielicka 265, Department of Clinical Chemistry and Clinic of Metabolic Diseases*, Kopernika 15, Cracow, Poland

The aim of this study was to compare lipoproteins and apoproteins levels in serum of 88 diabetic children and 23 obese children. The children were divided into sex and age groups: 3-11 and 11-19 years old boys and 3-10 and 10-19 years old girls. The control group of 52 healthy children matched on sex and age was included. The duration diabetes was I to 15 years. Insulin MS Actrapid and Monotard in 2 injectionis/24 hours with diabetic diet in 6 meals/24 hours were used for diabetes treatment. The obesity in children was about 50% of overweigth. Triglycerides, total cholesterol were measured enzymatically (Boehringer Mannh) VLDL was isolated by ultracentrifugation at d=I.006 g/ml, HDL cholesterol was determined after heparin-manganese precipitation, LDL cholesterol was calculated from Friedewald formula, apo AI was determined by radial immunodifusion, apo B by rocket immunoelectrophoresis. In diabetic children compared with healthy children the significant increase of apo B, of the ratios: total cholesterol/HDL, apoB/apoAI, and the significant decrease of HDL 3 was obserwed. In obese children greater changes in lipoproteins and apoproteins were noticed. In this group of children the significant increase of LDL-cholesterol, apoB and the ratios: CH/HDL, LDL/HDL, apoB/apoAI, CH/apoAI was found with the significant decrease of HDL and HDL 2. These data demonstrate that in obese children there is the increase of atherogenic lipoproteins and the decrease of "antiatherogenic" lipoproteins while in diabetic children with well controlled diabetes apoB increase with HDL3 cholesterol decrease was obserwed. These results demonstrate that the obesity can induce more pronouced changes in lipoproteins and apoproteins levels than diabetes in children

POS-001-163 HYPERLIPIDEMIAS IN OBESE DIABETICS.

VRR KODALI, V SESHIAH, SV RAMAN, VS GANESAN, A SUNDARAM

Dep~rtment of Diabetology, Madras Medical College, Madras-600003, India.

Hyperlipidemias occur more frequently in Diabetics, however the differences in their pattern with varying body mass are not much studied. We studied hyperlipidemias in 364 freshly detected Non-insulin dependent diabetics and grouped them according to sex and body mass Index (BMI). Total choles- terol (TC)~250 mg/dl and Triglycertides (TG)7175 mg/dl were taken to in- clude under hyperlipidemia. BMI of~27 for men orTz25.0 for women was taken to classify as obese. Men with BMI<18.0 and women with <16.6 were classified as undernourished. Fifty three percent of obese men had one or other type of hyperlipidemia (n = 34, IIa 8.8; IIb 5.9; IV 38.2). Among those with normal BMI 33.2%had hyperlipidemia (n=141; IIa 9.1; IIb 9.9; IV 14.2). Of the 23 undernourished 56.5% had hyperlipidemia (IIa 26~I i IIb 8.7; IV 21.7). Hyperlipidemia was present in 62.2% of 74 obese women (IIa 27.0; IIb 12.~; IV 23.0) and in 53.5% of the 86 women with normal BMI (IIa 31.4; IIb 10.5; IV 11.6). In a small number (6) of undernourished women two had type IIb hyperlipidemia. The results show that hyper-lipidemia is a problem not only in obese but also in lean diabetics. The similar proportions of hyperlipidemias in the undernourished could be secondary to higher glucose levels found in them. This study highlights that a major proportion (51%) of Non-lnsulin dependent diabetics had some type of hyperlipidemia at the time of diagnosis. Thus it is necessary to estimate at least two of these components in all diabetics

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POS-001-164 EFFECT OF INSULIN TREATMENT AND INSULIN REGIMENS ON BLOOD LIPOPROTEIN AND APOLIPOPROTEIN CONCENTRATIONS IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES MELLITUS

T Lindstr~m, H Arnqv is t and AG Olsson, Department of In te rna l Medic ine, Facu l ty of Health Sciences, S-581 85 L ink~ping, Sweden

A l te red blood l i p i d s may con t r i bu te to the increased a the rosc le ros i s in d i a b e t i c pa t i en t s . The aim of t h i s study was to i n v e s t i g a t e the e f f e c t of i nsu l i n t reatment on blood l i p i d s in non- insu l in-dependent d i a b e t i c pa t ien ts wi th secondary f a i l u r e on oral hypoglycaemic agents. Ten pa t ien ts (mean age 57.6 years and BMI 20.3 - 28.8) were t rea ted with 2- and 4-dose i nsu l i n in a randomized crossover t r i a l . In 2-dose treatment i nsu l i n was given as a 15:85 % mixture of regu la r and in te rmed ia te act ing i nsu l i n before breakfas t and d inner . On 4-dose regu la r i n s u l i n was given p r e p r a n d i a l l y and in termedia te ac t ing a t bedtime. Each t reatment per iod was 8 weeks.

S im i la r glycaemic cont ro l was achieved on both t reatments. HbA1c decreased from 8.8 + 0.3 % (mean + SE) to 5.7 ÷ 0,1 on 2-dose and 5.6 + 0.2 on 4-dose (normal range 3.2-670). Total t r i g l ~ e r i d e s decreased from 1.7 + 0.2 mmolTl to 1.1 mmol/l on both treatments (p~O.05) and HDL-kolesterol increased f~om 0.9 + 0.08 mmol/l to 1.1 mmol/l (p~O,01). Both HDL~ and HDL 3 increased numer ica l l y but onTy the l a t t e r s i g n i f i c a n t l y . Apo l i pop ro te i r AI increased from 1.18 + 0.05 g / l to 1.29 g / l (p ,O.01) . There was no change in apo l i pop ro te in B c o n c e ~ r a t i o n .

In conclusion i n s u l i n t reatment of NIDDM with secondary f a i l u r e causes changes in the concentrat ions of l i p o p r o t e i n s and apo l i pop ro te ins and gives a pat te rn tha t is considered to be less atherogenic . The e f f ec t s were s i m i l a r on both treatments used.

POS-001-165 INCREASED FATTY ACID CLEARANCE BY SKELETAL MUSCLE DURING CARBOHYDRATE FEEDING IN VlVO IN RATS.

AB JENKINS, SM FURLER, and EW KRAEGEN Garvan Institute of Medical Research,St Vincent's Hospital, Sydney, Australia.

Increased lipid oxidation correlates with increased insulin resistance in obesity and type II diabetes. Fatty acids (FFA) are a major lipid fuel and we are therefore investigating the control of tissue-specific fatty acid uptake and metabolism in vivo using a radiolabelled 'non-metabolisable' fatty acid analogue tracer. 3H-2Br-palmitic acid (3HBrP) is taken up and processed by FFA-specific mechanisms by tissues in vivQ. Products are not oxidised but are effectively trapped in muscle and other tissues. The rate of BrP uptake is a good predictor of the rate of palmitate uptake in the perfused rat heart (Palmitate uptake = k • BrP uptake, k=7.1+1.5 (SEM), r=0.85, p<0.001).

Groups (n=5) of chronically cannulated conscious rats (Wistar 350g) received a systemic bolus of tracer 3HBrP after a 24hr fast without or during voluntary carbohydrate refeeding. The fasting-refeeding transition is thought to cause large changes in FFA metabolism. After 15 minutes, tissues were removed under anaesthesia and the rate of clearance of BrP into tissues was determined from the total 3H recovered in tissues and the plasma 3HBrP time course. Tissues compnsed seven hind limb skeletal muscles and diaphragm. Clearances (ml/(100g-min)) were compared with our published estimates of tissue-specific plasma flow rates in fasting rats.

BrP clearance in individual muscles in fasting rats was highly correlated with plasma flow (r=0.917, p<0.01) with a slope equivalent to 16% first pass extraction of BrP. If authentic fatty acid uptake is 7 times more efficient as in heart, fatty acid first pass extraction approaches 100% and uptake is effectively flow limited. Under these circumstances, the effective k is flow dependent and will be less than that obtained in head under non flow-limited conditions (i.e. <7.1+1.5) Carbohydrate refeeding produced a marked increase in BrP clearance in skeletal muscle compared to fasting (+89+10%, p<0.001) which may partially compensate for reduced circulating FFA (1.5_+0.5 vs 0.4+0.1 mmol/I). This increased clearance may be due to 1) feeding induced changes in muscle blood flow; 2) decreased saturation of specific fatty acid uptake mechanisms by reduced FFA concentration; or 3) adaptive processes within the muscle.

We conclude that FFA uptake by muscle is strongly influenced by variations in blood flow and that the capacity of muscle for FFA extraction varies under physiological conditions.

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POS-001-166 ALTERATIONS IN LIPOPROTEIN METABOLISM WITH CORONARY HEART DISEASE(CHD) IN NON-INSULIN DEPENDENT DIABETES MELLITUS(NIDDM)

TOHRU MURAKAMI, JYUNJI OKU, KIYOSHI KAWAKUBO AND TSUNEAKI SUGIMOTO DEPT. OF 2ND INTERNAL MEDICINE UNIVERSITY OF TOKYO, TOKYO, JAPAN

The serum lipoprotein profile was studied in NIDDM patients with (60 cases) and without CHD (134 cases). The patients with CHD were older in age(63±1 vs 57±1,mean±SE),more obese (BMI 23.2±0.3 vs 22.3±0.3) and had longer history of DM(14±1.2 vs 10±0.7) than those without CHD. Those with CHD had higher serum VLDL-TG(56±2 vs 50±2%) and lower LDL-TG(33±2 vs 38± 1%)when compared in terms of percentage. No differences were noted in HDL- Chol and LDL-Chol levels. Then the patients were divided into hyperlipemic and normolipemic groups according to the serum lipid level (2230 vs <230mg/dl in TC and/or 2150 vs <150mg/dl in TG). In the normolipemic group, there were differences in age (64±2 vs 57±I) and BMI(23.3±0.5 vs 21.6±0.3) but no differences in the lipoprotein levels between the patients with (32) and without CAD (81).In the hyperlipemic group clinical pictures were not different while lipoprotein profiles were different as below.

n total chol (HDL LDL VLDL) total TG (HDL LDL VLDL) CAD(+) 20 238±10mg/dl (22±2 51±3 27±3%) 193±22mg/dl (10±I 26±2* 64±3*%) CAD(-) 46 243±7 (25±2 54±2 21±2 ) 181±12 (11±I 35±2 54±3 )

*: p<0.05 compared to CAD(-) In conclusion, alterations in lipoprotein metabolism was found to be

associated with CHD in hyperlipemic NIDDM but not in normolipemic NIDDN.

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