Abnormal Lipoprotein Patterns Research Articles

The influence of systemic inflammation and autoimmunity to serum lipid in patients with rheumatoid arthritis

ObjectiveThe purpose of this study was to determine whether inflammation state and autoimmune antibodies are associated with increased lipid in those with rheumatoid arthritis (RA).MethodsA total of 402 RA patients...

Lipid Profiles in Patients with Rheumatoid Arthritis: Mechanisms and the Impact of Treatment

To describe the impact of rheumatoid arthritis (RA), and its treatment, on lipoprotein levels with potential implications for atherosclerosis. A PubMed literature search was undertaken for studies published between 1990 and May 2007, using the search terms "rheumatoid arthritis" AND "lipid" OR "lipoprotein," and including all relevant drug treatment terms for glucocorticoids, disease-modifying antirheumatic drugs, and biologics. Patients with RA face an increased risk of developing premature cardiovascular disease and limited ability to modify risk factors, eg, through exercise. RA is associated with an abnormal lipoprotein pattern, principally low levels of high density lipoprotein (HDL) cholesterol. Most treatments for RA tend to improve the atherogenic index (total/HDL cholesterol ratio), with more evidence for biologics in this regard. The improvement in the lipoprotein profile in RA appears to be associated with suppression of inflammation. Lipid levels should be monitored and managed in patients with RA to minimize the long-term risk of cardiovascular disease. More research is needed to quantify the relationship between systemic inflammation and lipoprotein levels and to determine the impact of specific lipoprotein particles, eg, small dense low-density lipoprotein and subfractions of HDL on long-term risk. Control of inflammation may have an effect on modifying cardiovascular risk.

Clinical significance of abnormal lipoprotein patterns in liver diseases

We analyzed lipids in liver diseases by agarose gel electrophoresis, and differential staining and simultaneous analysis of the cholesterol (Chol) and triglyceride (TG) fractions. Liver diseases were classified into chronic hepatitis (CH), liver cirrhosis (LC), hepatocellular carcinoma (HCC), and metastatic liver cancer, and each fraction was compared among these diseases. Atypical patterns that were unclassifiable according to the WHO classification of hyperlipidemia phenotypes were classified, and their clinical importance was evaluated. With progression of the pathologic conditions of CH, LC, and HCC, the T-Chol level, each Chol fraction, and the TG fraction decreased while the LDL-TG fraction increased. Metastatic liver cancer showed a lower HDL-fraction level but higher levels of the other parameters than HCC. When the subjects were classified into survivors and patients who died, the HDL fraction level in HCC and metastatic liver cancer, and the LDL level in LC and metastatic liver cancer differed between survivors and patients who died. Phenotypes of hyperlipidemia also differed among diseases, and atypical patterns were frequently observed in patients who died. There were 6 atypical patterns, of which 4 (slow alpha HDL, abnormal LDL, Lp-X, and Lp-Y) were associated with liver diseases. Slow alpha HDL appeared during slight bile stagnation and was accompanied by increases in the apo E level and the HDL particle size. Abnormal LDL appeared with severe liver dysfunction; a TG peak appeared at the position of LDL, and the HDL and VLDL fractions were negligible. Lp-X was a Chol-rich band, occurring on the cathode side of LDL in the presence of marked bile stagnation such as that in obstructive jaundice, and was accompanied by appearance of abnormal LDL. Lp-Y was similar to Lp-X in terms of mobility and associated diseases but contained Chol and TG. Abnormal LDL, Lp-X, and Lp-Y were often observed in patients with poor outcomes. Lipid analysis in liver diseases by this method showed results reflecting the pathologic conditions and may be clinically useful.

Renal dysfunction as a novel risk factor: Microalbuminuria and cardiovascular risk

only for elevated glucose or BMI values; the correlation extends well into the range of normal values. Apparently, the metabolic syndrome and microalbuminuria are tightly correlated with each other. This relation is of considerable interest because in patients with renal disease insulin resistance is found even in the very early stages [10], and even when GFR is still within the normal range (unpublished observations). Conversely, in a population sample it was found that insulin resistance (according to the HOMA index) was associated with a higher risk of chronic kidney disease [11]. The information obtained from microalbuminuria cannot be replaced by estimating the glomerular filtration rate. Although the reports in the literature are not entirely consistent, the study in Groningen showed that with increasing quantiles of urinary albumin excretion, the creatinine clearance tended to be higher and was lower only in the uppermost quantiles [12]. Although the creatinine clearance is not a reliable index of glomerular filtration, this observation would be plausible in view of a similar relation between GFR and albuminuria noted previously in diabetic patients [13]. There has been much discussion whether microalbuminuria reflects primarily a generalized endothelial cell dysfunction, as suggested by the Steno hypothesis [14], or whether it reflects a podocyte defect, as proposed more recently [15]. The observation that the rate of albumin escape from the plasma space is increased in patients with microalbuminuria [16] argues for the former possibility. The observation that the risk of being microalbuminuric was significantly higher for carriers of the Q-genotype of the 229 polymorphism of the podocin gene at any given level of body mass index or other correlates of microalbuminuria is more in favor of a podocyte problem [15].

Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation

Cremophor EL (CrEL) is a formulation vehicle used for various poorly-water soluble drugs, including the anticancer agent paclitaxel (Taxol). In contrast to earlier reports, CrEL is not an inert vehicle, but exerts a range of biological effects, some of which have important clinical implications. Its use has been associated with severe anaphylactoid hypersensitivity reactions, hyperlipidaemia, abnormal lipoprotein patterns, aggregation of erythrocytes and peripheral neuropathy. The pharmacokinetic behaviour of CrEL is dose-independent, although its clearance is highly influenced by duration of the infusion. This is particularly important since CrEL can affect the disposition of various drugs by changing the unbound drug concentration through micellar encapsulation. In addition, it has been shown that CrEL, as an integral component of paclitaxel chemotherapy, modifies the toxicity profile of certain anticancer agents given concomitantly, by mechanisms other than kinetic interference. A clear understanding of the biological and pharmacological role of CrEL is essential to help oncologists avoid side-effects associated with the use of paclitaxel or other agents using this vehicle. With the present development of various new anticancer agents, it is recommended that alternative formulation approaches should be pursued to allow a better control of the toxicity of the treatment and the pharmacological interactions related to the use of CrEL.

Standard treatment of alpha-tocopherol in Alagille patients with severe cholestasis is insufficient.

Alpha-tocopherol (alpha-T) is the most effective lipid-soluble antioxidant present in cells. We investigated the efficacy of alpha-T supplements for preventing lipid peroxidation in patients with Alagille syndrome, according to the severity of cholestasis. Patients were assigned to two groups on the basis of plasma bilirubin concentration (group I, bilirubin <100 microM; group II, bilirubin >100 microM). alpha-T concentrations were determined in plasma, in isolated lipoproteins, and in red blood cell membranes. In both groups of patients, alpha-T concentrations in plasma were similar to those in control subjects, but the distribution of alpha-T in lipoproteins was affected by the abnormal lipoprotein pattern in these patients. The efficacy of alpha-T was estimated by determining the amount of hydroperoxide produced from phosphatidylcholine and phosphatidylethanolamine (PE) molecular species owing to oxidative stress induced by lipoxygenase treatment. The concentrations of phosphatidylcholine molecular species and its corresponding hydroperoxides were significantly higher in both groups of patients. In group I, alpha-T and PE molecular species concentrations were similar to those in control subjects, but PE hydroperoxide concentrations were higher than those in the control subjects. In group II, alpha-T concentration was significantly lower and the concentrations of some PE molecular species and all PE hydroperoxides were lower than those in the control subjects. In conclusion, erythrocyte membrane alpha-T concentration was significantly lower only in patients with severe jaundice, despite alpha-T supplementation, raising the question as to whether the usual treatment was appropriate in this group.

Abnormal lipoprotein pattern in patients with Alagille syndrome depends on Icterus severity

BACKGROUND & AIMS: Children with Alagille syndrome have lipid abnormalities that differ according to the severity of icteric periods. The lipoprotein profiles of 22 patients with Alagille syndrome were determined and the findings were compared with the severity of jaundice. METHODS: Plasma lipids and apolipoproteins (apos), isolated lipoprotein composition, and lecithin/ cholesterol acyltransferase (LCAT) activity were analyzed in patients. Patients were classified into two groups according to their bilirubin levels; patients in group I had total bilirubin levels of > 100 mumol/L, and patients in group II had total bilirubin levels of < 100 mumol/L. RESULTS: In patients from group II, hypercholesterolemia was associated with increased levels of high-density lipoprotein and high concentrations of apoAI and apoAII; in a few cases, an abnormal lipoprotein with a slow alpha migration was observed. In contrast, in patients from group I, the levels of high- density lipoprotein cholesterol and apoAI and apoAII were very low, and the abnormal lipoprotein X was in many cases responsible for hypercholesterolemia. In group I, the decreased LCAT activity was consistent with the very high level of unesterified cholesterol and the emergence of lipoprotein X. In both groups of patients, the levels of apoE, apoCII, and apoCIII were high, and all the lipoprotein fractions were enriched in phospholipids. CONCLUSIONS: The variations of LCAT activity caused by the degree of jaundice in patients with Alagille syndrome are implicated in the abnormal lipid profiles. (Gastroenterology 1996 Oct;111(4):1023-32)

Long-term Treatment with Growth Hormone Decreases Plasminogen Activator Inhibitor-1 and Tissue Plasminogen Activator in Growth Hormone-deficient Adults

The syndrome of growth hormone deficiency (GHD) in adults is associated with premature atherosclerosis, increased cardiovascular mortality, abnormal lipoprotein patterns and abnormal body composition. We have previously shown that GH-deficient adults have increased concentrations of fibrinogen and plasminogen activator inhibitor (PAI-1) activity. The aim of the present investigation was to study coagulation and fibrinolysis in 17 patients with adult-onset GHD during two years of treatment with recombinant human GH (12 micrograms/kg body weight/day). The impact of the contemporary changes in metabolic variables and body composition on coagulation and fibrinolysis was studied. The patients received conventional thyroid, adrenal and gonadal hormone replacement therapy. PAI-1 activity, PAI-1 antigen and tissue plasminogen activator (t-PA) antigen levels decreased during the GH treatment period (p < 0.05). The decrease was more pronounced in patients with high pre-treatment levels of the different variables. alpha 2-antiplasmin decreased (p < 0.05), while plasminogen was unchanged during two years of GH treatment. Fibrinogen concentrations tended to decrease after two years of GH treatment (p = 0.06), while the coagulation factors VII and VIII were unchanged. von Willebrand factor demonstrated a transient decrease after 18 months of GH treatment. The coagulation inhibitor, protein C, decreased (p < 0.05), while antithrombin was unchanged. Fasting plasma insulin increased (p < 0.01), but blood glucose did not differ after two years of GH treatment. Serum high-density lipoprotein cholesterol, total cholesterol and triglycerides were unaltered. Body fat decreased during the initial GH treatment but was unaltered after two years, while lean body mass increased (p < 0.001) and the waist over hip circumference ratio tended to decrease (p = 0.06). In conclusion, PAI-1 activity, PAI-1 antigen and t-PA antigen decreased during long-term GH treatment. These changes may be a direct effect of GH itself or may be secondary to the favourable changes in body composition. It remains to be seen whether changes in these fibrinolytic variables during rhGH treatment reduces the cardiovascular risk in patients with GHD. The present results suggest that GH plays a role in the regulation of fibrinolysis.

Increased level of hemoglobin A 1C, but not impaired insulin sensitivity, found in hypertensive and normotensive smokers

Smoking is associated with an abnormal plasma lipoprotein pattern. Recently, both insulin resistance and normal insulin action have been reported in smokers. In a total of 191 hypertensive and normotensive subjects recruited from a health survey, serum lipoprotein lipids, glucose tolerance (by intravenous glucose tolerance test (IVGTT), insulin secretion, and insulin sensitivity (euglycemic insulin clamp) were compared in the 41 smokers and 150 nonsmokers. Subjects were examined in the morning during a fasting state and after abstinence from smoking for 10 to 12 hours. Smokers showed a higher level of hemoglobin A 1c (HbA 1c) as compared with nonsmokers, 4.9% versus 4.7% ( P < .05). There were no significant differences in fasting glucose, insulin, or insulin-mediated glucose disposal. However, a number of indices of insulin sensitivity tended to show enhanced insulin action among smokers. Only lower glucose and insulin values during the late phase (40 to 90 minutes) of the IVGTT reached statistical significance. Compared with nonsmokers, smokers had an expected higher level of serum triglycerides (2.1 v 1.8 mmol/L, P < .05) and an increased low-density lipoprotein (LDL) to high-density lipoprotein (HDL) cholesterol ratio (4.5 v 3.9, P < .05). These differences between smokers and nonsmokers were similar in both hypertensives and normotensives. In conclusion, smokers examined in the abstinence phase showed no signs of impaired insulin action. Lipoprotein abnormalities and elevated HbA 1c may be caused in part by the insulin resistance induced during acute smoking and therefore may be quantitatively related to the time exposed to smoking. The effect on insulin sensitivity appears to be reversible over 10 to 12 hours.

Lipoprotein Profiles in Hypercholesterolemic Children

Atherosclerosis is a process that begins in early life. Coronary heart disease is the result of complex interactions among a variety of risk factors of which hypercholesterolemia is but one. During routine screening, 500 children were identified with total cholesterol levels above the 95th percentile of 5.2 mmol/L (200 mg/dL). Lipoprotein profiles were then performed to confirm and delineate their lipid abnormalities. A definable lipid disorder was present in 85% of such children. Abnormal lipoprotein patterns included 292 children with type IIa, 99 with type IIb, and 25 with type IV phenotypes. An abnormally low high-density lipoprotein cholesterol level of less than 0.9 mmol/L (35 mg/dL) was observed in 20 children. Only 5% of patients were identified as being hypercholesterolemic because they had high-density lipoprotein cholesterol levels above the 95th percentile of 1.8 mmol/L (70 mg/dL). Thirty-two percent of children with total cholesterol levels above 5.2 mmol/L had a family member (sibling, parent, uncle, aunt, or grandparent) with a myocardial infarction prior to 55 years of age. Data from this study support universal cholesterol testing after 3 years of age and lipoprotein profiles for those with levels above 5.2 mmol/L.

Plasma and lipoprotein fatty acid composition in glycogen storage disease type I.

Nocturnal intragastric feeding has been shown to be an effective means to improve clinical and biochemical features in glycogen storage disease type I (GSD-I). In this study, we investigated the fatty acid patterns in a whole plasma and in circulating lipoproteins in patients on this therapy. The results demonstrated massive concentration of total fatty acids coupled with higher levels of triglycerides, free cholesterol, cholesterol ester and phospholipids. This hyperlipidemia involved all fatty acids without distinction of carbon or bond numbers. However, the increase was more pronounced for saturated than polyunsaturated fatty acids, as was demonstrated by the ratios of both oleic acid to linoleic acid (1.91 +/- 0.40 vs 0.80 +/- 0.09 in controls) and of omega 3 + omega 6 to omega 9 fatty acid families (0.92 +/- 0.11 vs 1.66 +/- 0.08 in controls). The fatty acid patterns in very low (VLDL), low (LDL) and high (HDL) density lipoprotein showed substantial differences in composition, reflecting an association between an abnormal lipoprotein pattern and essential fatty acid deficiency. Furthermore, GSD-I patients exhibited a significant increase in VLDL (17 +/- 2 vs 47 +/- 7 mg/dl) and LDL cholesterol (124 +/- 7 vs 206 +/- 24 mg/dl), coupled with a decrease in HDL cholesterol (49 +/- 4 vs 28 +/- 3 mg/dl). These data documenting high LDL cholesterol and low HDL cholesterol associated with an increased concentration and proportion of saturated fatty acids suggest that GSD-I patients on nocturnal intragastric feeding are at high risk for atherosclerosis and its complications.

Correlation of Dairy Food Intake with Human Antibody to Bovine Milk Xanthine Oxidase

SummarySeventy-three out of 94 human subjects were found to have antibodies to BMXO. Individuals with no BMXO titer had the lowest dairy food consumption of the population tested and there appears to be an inverse relationship between increased dairy fat consumption and decrease in IgA and IgM concentrations in titer groups 1-4. When divided into arbitrary groups according to the geometric mean titer, BMXO titers were higher as the milkfat and whole milk consumption increased (Fig. 1). Multiple regression analysis of the data indicated highly significant correlations (P < 0.0001) between milkshake consumption, milk consumption in early life, abnormal lipoprotein patterns, low serum glucose level and the incidence of tonsillectomy at age 10 or later with the presence of antibodies to BMXO. These correlations and the observation that higher milkfat and whole milk consumption resulted in higher BMXO titers suggest the uptake of dietary BMXO from the gut.

Broad-β disease versus endogenous hypertriglyceridemia: Levels and lipid composition of chylomicrons and very low density lipoproteins during fat-free feeding and alimentary lipemia

To assess the roles of endogenous and exogenous lipid in the production of the abnormal lipoprotein patterns characteristic of broad-β disease (with a type III lipoprotein pattern) and endogenous hypertriglyceridemia (with a type IV pattern), oral fat loads (50 g/M 2) were administered to six subjects with broad-β disease and to eight with endogenous hypertriglyceridemia following at least 72 hr of 0% fat, 85% carbohydrate isocaloric formula feeding. Total plasma and S f > 400, 100–400, 60–100, 30–60, and 20–30 lipoprotein cholesterol, triglyceride, and phospholipid levels were measured at 0 hr, 6 hr (at or before the peak of alimentary lipemia), and 24 hr following the fat load. Following fat-free feeding the levels and composition of the endogenous S f > 400 lipoproteins were similar in both disorders; whereas total S f20–400, and most notably, S f30–60 and 20–30 levels were increased and enriched in cholesterol in the subjects with broad-β disease. The latter phenomenon persisted both early and late following the oral fat load. At peak alimentary lipemia, chylomicrons were equally increased and triglyceriderich in both subject groups, but by 24 hr this fraction was becoming more enriched in cholesterol in the group with broad-β disease. These experiments thus suggest that both endogenous and exogenous triglyceride-rich lipoproteins are of normal composition when first secreted in broad-β disease, but become abnormal during their catabolic conversion to lipoproteins of higher density.

Mass Screening for Coronary Risk Factors in 2,524 Asymptomatic Adults

The prevalence of coronary risk factors was assessed in 2,524 asymptomatic adults in Long Beach, California. Hypercholesterolemia (serum cholesterol level greater than 250 mg/100 ml) was present in 725 subjects (28.8 per cent), hypertriglyceridemia (serum triglyceride level greater than or equal to 150 mg/100 ml) in 497 (19.7 per cent), and an abnormal lipoprotein pattern in 813 (32.2 per cent). Of the 2,524 subjects, 233 (9.2 per cent) had a blood pressure above 140/90 mm Hg and 116 (4.6 percent) had a blood pressure above 150/100 mm. There were 1,043 cigarette, cigar, or pipe smokers (41.3 per cent). Fifty subjects (2.0 per cent) had a fasting blood sugar level above 120 mg/100 ml, 48 (1.9 per cent) had abnormal triceps skinfold thickness, and 382 (15.2 per cent) weighed 20 per cent or more above the desirable weight. The electrocardiogram during rest was definitely above the desirable weight. The electrocardiogram during rest was definitely abnormal in 183 subjects (7.3 per cent). On the basis of these data it is evident that in many asymptomatic adults, risk factors predisposing to coronary disease are not being detected or treated.

Familial Hyperlipidemias

Hyperlipidemias represent a group of metabolic disorders characterized by an increase in plasma cholesterol or triglycerides, or both. Cutaneous or tendon xanthomas may or may not be present, depending on the severity of the lipid abnormality. A high incidence of coronary heart disease is a prominent feature in some forms of familial hyperlipidemias. Besides plasma lipid levels, the determination of plasma lipoprotein patterns adds a new criterion to the identification of this group of heterogeneous disorders. On the basis of abnormal lipoprotein patterns, five types of familial hyperlipidemias have been recognized. The interpretation of abnormal lipoprotein patterns is not only of diagnostic importance but also may reveal useful information as to the possible mechanism of a lipid metabolic derangement. Furthermore, a correct diagnosis is of the utmost importance to arrive at the proper treatment.

FREQUENCY OF RISK FACTORS FOR ISCHÆMIC HEART-DISEASE IN A HEALTHY BRITISH POPULATION: WITH PARTICULAR REFERENCE TO SERUM-LIPOPROTEIN LEVELS

The concentration of cholesterol and triglyceride in serum and in its lipoprotein classes has been measured in 276 carefully screened men and women aged 20-69 years, living in London, to ascertain the frequency of hyperlipidæmia and of abnormal lipoprotein patterns. The quantitative procedure of preparative ultracentrifugation was used. 4·3% of men and 4·8% of women aged 40-69 years had serum-cholesterol concentrations exceeding 300 mg. per 100 ml.; 14% and 3% of men and women had triglyceride levels greater than 2·0 mmol per litre. By these definitions, 17% of men and 8% of women had hyperlipidæmia. Physical signs suggesting hyperlipidæmia, such as xanthelasma, were rare. About one in twelve subjects had blood-pressures of 160/ 100 mm. Hg or more, and hyperuricæmia was also frequent. Even when cut-off points for I.H.D. lipid and other risk-factors were intentionally set high, their prevalence in this healthy working population was very substantial. Age and sex differences in lipid levels were noted, serum-triglyceride concentration being considerably higher in men. The abnormal lipoprotein patterns seen were raised levels of very-low-density (prebeta) lipoprotein (V.L.D.L.), of low-density (beta) lipoprotein, and of both lipoproteins. In a few subjects the cholesterol but not the triglyceride content of V.L.D.L. exceeded the 95th percentile. Triglyceride concentrations correlated positively with indices of obesity, and were slightly higher in women using oral contraceptives.

Studies of hyperlipidemia in the HGH-deficient state

Plasma lipoproteins were analyzed in seven subjects with an isolated deficiency of human growth hormone (HGH). By plasma lipoprotein electrophoresis, each had a prominent beta band, and five also exhibited a strongly staining prebeta band. The prominent beta band was associated with elevation of plasma cholesterol and low density lipoprotein (LDL), while the increased prebeta band appeared to reflect the high levels of plasma triglycerides and very low density lipoproteins (VLDL). Glucose tolerance was abnormal in each subject, but basal plasma free fatty acid (FFA) and insulin concentrations were within the normal range. The data indicate that growth hormone deficiency is associated frequently with an abnormal serum lipoprotein pattern, and that, either directly or indirectly, the pituitary modulates serum lipoprotein metabolism. Cardiovascular disease was conspiciously absent in this group, a finding that will require further investigation.

Serum lipids and lipoproteins in children from families with early coronary heart disease.

Serum lipids and lipoproteins of 64 men under the age of 41 years who survived for more than 6 months after a myocardial infarction, and of their children were investigated. 26 fathers and all their 55 children had normal serum lipids and lipoprotein patterns. 38 fathers had normal serum lipid concentration and abnormal lipoprotein pattern; of these, 23 had hyper-β-lipoproteinaemia, 11 had increase in both β- and pre-β-lipoprotein, and 4 had increase in pre-β-lipoprotein only. 30 of the 85 children whose fathers had abnormal lipoproteins were found to have type II hyperlipoproteinaemia regardless of the class of hyperlipaemia found in the father. The greatest incidence of lipoprotein abnormality was found in children of fathers of hyper-β-lipoproteinaemia.

Serum Lipoprotein Deficiency in Diffuse "Normolipemic" Plane Xanthoma

A case of xanthomatous skin changes and an abnormal serum lipoprotein pattern is described. The clinical and histological findings are those of diffuse normolipemic plane xanthoma. The main features of the case are intracellular cholesterol deposits in the skin, and in serum, a reduced level of total high-density lipoproteins and also an abnormally low cholesterol content of the low-density and very low-density lipoprotein fractions. The case does not correspond to any of the types of lipoprotein abnormality in the classification of Fredrickson and Lees. It shows some similarities to the two conditions of α-lipoprotein deficiency, Tangier disease, and familial lecithin-cholesterol-acyltransferase deficiency. The case appears to represent a type of lipoprotein abnormality, not previously reported.

Plasma lipoproteins in adult diabetes.

SUMMARYThe prevalence of hyperlipoproteinaemia was investigated in three groups of diabetics. Of 106 untreated diabetics. Of 106 untreated diabetics 68% had some form of hyperlipoproteinaemia. When the plasma of fifty‐six of these patients was re‐examined after their hyperglycaemia was controlled, then only 22% had an abnormal lipoprotein pattern. A further group of 102 diabetics who had been receiving treatment for between 1 and 34 years and whose hyperglycaemia appeared to be well controlled were also studied and the prevalence of abnormal lipoprotein patterns in this group was 58%. There was no correlation between the age of the patient and the prevalence of hyperlipoproteinaemia but all those studied were over 30 years of age.There was no evidence that any of the forms of treatment used, diet alone, diet with sulphonylureas, diet with phenformin, or diet and insulin was more successful than any of the others either in reducing the overall prevalence of hyperlipopro‐teinaemia or in treating any particular type of hyperlipoproteinaemia.