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Lipid metabolism was evaluated during management of phaeochromocytoma in a 41 year old non-obese post-menopausal women with familial combined hyperlipidaemia. The main effect of the excess catecholamine secretion on lipid metabolism was increased lipolytic activity, lower serum triglyceride and increased HDL cholesterol concentrations, compared with findings following removal of the tumour. Before removal of the tumour, the use of beta blockers alone led to marked deterioration of the hyperlipidaemic state, and combined alpha and beta blockade additionally led to a marked reduction in fat oxidation and lipoprotein lipase activity. Overactivity of the adrenergic system leads to changes in lipid metabolism in phaeochromocytoma. Treatment of the phaeochromocytoma may lead to worsening of hyperlipidaemia pre-existing in such individuals. [ABSTRACT FROM PUBLISHER]

A 15 year old girl with a family history of type 1 multiple endocrine adenomatosis presented with reversible neurological disturbances, hypoglycaemia and hyperinsulinaemia. Initial radiology was normal, but portal venous sampling suggested an insulinoma in the tail of the pancreas which was removed with conservation of the spleen. Hypoglycaemia persisted despite high doses of diazoxide and intravenous dextrose. A second laparotomy revealed a pancreatic endocrine tumour and sub-total pancreatectomy was performed. Histology revealed islet cell microadenomatosis. Hypoglycaemia persisted despite treatment with somatostatin analogues and 40% intravenous dextrose was required to maintain normoglycaemia. A possible lesion near the splenic hilum on computed tomographic scan was reported as a splenunculus although further peripheral, hepatic and portal venous sampling suggested hepatic or systemic lesions. A positron emission scan and selective visceral angiography suggested a lesion in the left upper quadrant. Acute lactic acidosis, rhabdomyolysis and renal failure supervened. Post mortem revealed the putative 'splenunculus' to be a residual insulinoma, whilst the splenic vein was thrombosed, accounting in part for discrepant venous sampling data. Hyperinsulinaemia in type 1 multiple endocrine adenomatosis may require more aggressive surgical and hormonal intervention than when dealing with solitary insulinomas. Insulinomas may mimic developmental abnormalities on computed tomographic scanning. [ABSTRACT FROM PUBLISHER]

A 75 year old maturity-onset diabetic developed persistent local allergy to insulin. She had coexistent asymptomatic chronic lymphatic leukaemia. All species of insulin provoked a recurrence of the allergy and attempts at hyposensitization and treatment of the leukaemia produced only marginal benefit. Administration of subcutaneous steroids with insulin relieved the problem, but could not be stopped without relapse. Immunological investigations suggested an immune complex-mediated hypersensitivity reaction to insulin. The later development of immune complex-mediated arthropathy tended to support this suggestion. The lack of histological and immunological evidence of an IgE-mediated reaction suggested that in this case the mechanism of insulin allergy and arthralgia was IgG mediated. We suggest that the chronic leukaemia was implicated in both processes by interfering with homeostatic mechanisms that normally prevent the development of autoallergic disorders. [ABSTRACT FROM PUBLISHER]

Lipoprotein(a) [Lp(a)] concentration and apolipoprotein(a) [apo(a)] isoforms (identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE] and Western blotting) were determined in a group of 508 asymptomatic Caucasian members of the community and in 318 Caucasian patients with angiographically defined coronary artery disease (CAD). Conventional risk factors for CAD were also measured. Lp(a) concentration was almost twice as high in subjects with CAD (geometric mean, 152 mg/L [geometric SD, 10 to 1398 mg/L]) as in asymptomatic control subjects (geometric mean, 84 mg/L [geometric SD, 21 to 334 mg/L]). Asymptomatic women had higher concentrations of Lp(a) than asymptomatic men. Patients with CAD were older and were more likely to have smoked and to have a first-degree relative with premature CAD (< 55 years of age), and a higher proportion were male. Patients with CAD had higher concentrations of Lp(a) independently of the number of isoform bands expressed. When apo(a) isoforms were allocated to 1 of 10 classes on the basis of their molecular size (Rf versus apoB in SDS-PAGE), patients with CAD did not express an excess of low-molecular-mass (higher concentration) isoforms but did express a higher proportion of double-band phenotypes with fewer "null" phenotypes. The relationship between the two isoform bands in a double-band phenotype was the same in both populations. Isoform mobility was defined as a continuous variable equal to the mobility of a single isoform band (single-band phenotypes) or the mean of the two isoforms in a double-band phenotype. Two variables, isoform mobility and the number of isoform bands expressed, were used to summarize the large range of isoform patterns (at least 45) that could be identified. Isoform mobility, the number of isoform bands expressed, and the presence of CAD were the three most important independent predictors of Lp(a) concentration (descending order). Only sex and LDL cholesterol were additional independent predictors of Lp(a) concentration in step-wise regression models including a wide range of demographic factors and lipid and glycemic risk factors. We conclude that Lp(a) concentration is associated with CAD independently of the isoform pattern expressed. The apo(a) gene locus exerts a strong control over circulating Lp(a) concentration, and a better understanding of the control of expression of the apo(a) gene will be essential to understand the relationship between Lp(a) and CAD.

Objective: To examine whether impaired glucose tolerance and raised Lp(a) lipoprotein concentrations are associated in subjects with coronary artery disease., Design: Study of two subject populations, one with and one without symptomatic coronary artery disease. Case-control analysis of patients with impaired glucose tolerance and normal glucose tolerance performed in each subject population independently., Setting: A general practice and a hospital ward in Newcastle upon Tyne., Subjects: 517 apparently healthy subjects, 13 with impaired glucose tolerance, and 245 patients who had undergone coronary artery bypass graft surgery 12 months before, 51 with impaired glucose tolerance., Main Outcome Measures: Serum Lp(a) lipoprotein concentration, plasma glucose concentration before and after oral challenge with 75 g glucose monohydrate, and Lp(a) lipoprotein isoforms., Results: In both the asymptomatic subjects and the subjects with coronary artery disease there was no significant difference between subjects with impaired glucose tolerance and subjects with normal and body mass index in serum Lp(a) lipoprotein concentrations (geometric mean 61 (geometric SD 4) mg/l v 83 (5) mg/l for asymptomatic subjects, 175 (3) v 197 (2) for subjects with heart disease), nor was there any difference in the proportion of subjects who had Lp(a) lipoprotein concentrations > 300 mg/l (31% v 23% for asymptomatic subjects, 37% v 37% for subjects with heart disease). For both subject groups there was no significant correlation between Lp(a) lipoprotein concentration and plasma glucose concentration after a glucose tolerance test, nor did Lp(a) lipoprotein concentration vary by quintile of glucose concentration after the test. Examination of Lp(a) lipoprotein isoforms in the subjects with coronary artery disease revealed an inverse relation between isoform size and plasma Lp(a) lipoprotein concentration, but there was no evidence that impaired glucose tolerance was associated with particular Lp(a) lipoprotein isoforms., Conclusion: Raised Lp(a) lipoprotein concentrations are not responsible for the association between impaired glucose tolerance and coronary artery disease.

Lipoprotein composition was determined using ultracentrifugation in 20 non-insulin-dependent (NIDDM) diabetic patients on diet only (D), 20 NIDDM patients on diet and sulfonylurea therapy (T), and 20 nondiabetic control subjects (C), all of whom had total plasma cholesterol concentrations < 6.5 mmol/L and total plasma triglyceride concentrations < 3.0 mmol/L. Although the groups were well matched for age, body mass index, total triglyceride levels, and total cholesterol concentrations, there were significant compositional abnormalities in the low-density lipoprotein (LDL) fractions of diabetic subjects. The LDL total lipid to apolipoprotein B weight ratio (representing the density distributions of LDL particles) was reduced in both diabetic groups: 3.75 +/- 0.3, 3.50 +/- 0.28, and 3.54 +/- 0.22 in C, D, and T groups, respectively (mean +/- SD; P < .05). This was associated with a significant shift in the hydrated density distributions of LDL in the diabetic groups, with the average peak densities being 1.0320 g/mL (in C), 1.0365 g/mL (in D), and 1.0380 g/mL (in T) (P < .05). The LDL particles were also smaller in the NIDDM patients: 21.1 +/- 0.7, 20.4 +/- 0.5, and 20.6 +/- 0.5 nm in C, D, and T groups, respectively (P < .05). When the NIDDM groups were analyzed together, the LDL peak density was found to correlate with both insulin resistance (measured by a modified Harano technique; r = 0.37, P < .015) and total triglyceride concentrations (r = 0.40, P < .01). The results show that diabetic patients have small, dense LDL particles, which may be related to insulin resistance, and that these occur with minimal elevations of total triglyceride concentrations. These potentially atherogenic changes may contribute to the increased coronary heart disease in diabetic patients with mild hyperlipidemia.

To identify abnormalities of serum lipoprotein composition and concentration that were specific to insulin-dependent diabetes mellitus (IDDM), the procedure of discontinuous gradient ultracentrifugation was employed to isolate lipoprotein fractions in 44 patients with IDDM, 24 nondiabetic subjects with similar lipid and lipoprotein concentrations, and 19 healthy normocholesterolemic (less than 5.2 mmol/l [less than 200 mg/dl]) subjects. The mass concentration of low density lipoprotein (LDL) was greater in IDDM than in both control groups. The free cholesterol to phospholipid ratio in large very low density lipoprotein (VLDL) was greatest in IDDM in comparison with both of the other groups. The contribution of triglyceride to total large VLDL mass was greater, whereas that of phospholipids was lower, in IDDM than in the dyslipidemic nondiabetic group. Protein concentration was reduced and phospholipid increased in small VLDL in IDDM in comparison with both control groups, and the contribution from protein to lipoprotein mass was least in IDDM. Similarly in intermediate density lipoprotein (IDL), the protein concentration and its contribution to overall mass was also lower in IDDM than in either control group, but by contrast, the phospholipid content was increased. The cholesteryl ester to protein ratio was highest in both small VLDL and IDL in IDDM in comparison with both control groups, whereas the free cholesterol to phospholipid ratio in IDL was least in IDDM. In LDL, total cholesterol and triglyceride concentrations were greatest and the contribution from protein to lipoprotein mass was least in IDDM in comparison with both control groups. The LDL free cholesterol to phospholipid ratio was greater in IDDM than in dyslipidemic control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered lipoprotein composition may be a better predictor of cardiovascular disease than modestly increased serum lipid concentrations, although possible interactions between lipoprotein composition, obesity, and insulinemia have not been fully elucidated. Therefore, we investigated the association between different measures of insulinemia and lipoproteins in 297 healthy Caucasian men (body mass index [BMI] less than 27 in 233, greater than 27 [obese] in 64) and 295 healthy Caucasian women (BMI less than 25 in 198, greater than 25 [obese] in 97). Associations observed in both obese and nonobese men and women were between increasing tertiles of most insulin measures and serum triglyceride concentrations (p = 0.079-0.004) and the ratio of low density lipoprotein to high density lipoprotein cholesterol (p = 0.094-0.008). Graded reductions in the high density lipoprotein cholesterol to apolipoprotein A-I ratio were also recorded in obese women, with increasing tertiles of fasting (p = 0.014-0.007) and postglucose load (p = 0.001) serum insulin levels, after correcting for BMI and triglyceride concentrations. Less marked graded increases in the triglyceride to apolipoprotein B ratios were recorded in obese women with increasing tertiles of fasting (p = 0.001-0.006) and postglucose challenge (p = 0.081) insulinemic measures. In men with normal or slightly elevated cholesterol levels (fasting serum cholesterol less than 6.5 mmol/l), hyperapobetalipoproteinemia was recorded with increasing tertiles of insulinemia (p = 0.006, correcting for BMI and triglyceride concentrations), as well as in subjects with hypertriglyceridemia (fasting serum triglycerides greater than 1.70 mmol/l) (p = 0.004, correcting for BMI and age). Hyperinsulinemia and insulin resistance are associated with altered lipoprotein composition in obese women, presumably reflecting a complex interplay between sex hormones, body mass, and insulin action. Insulin resistance appears to be more associated with apolipoprotein B concentrations in men. The hyperinsulinemic nondiabetic subject may be at increased risk of cardiovascular disease because of altered concentrations of apolipoprotein concentrations and lipoprotein composition.

Patients with insulin dependent diabetes mellitus who develop proteinuria may die prematurely, whereas those who do not develop this complication have a comparatively normal life span. The excess mortality in diabetics with proteinuria is from cardiovascular as well as renal disease, but the reason is unclear. Risk factors for vascular disease were therefore assessed in 22 insulin dependent diabetics with proteinuria, but not renal failure, who were matched for sex, age, duration of diabetes, and glycated haemoglobin (HbA1) values with a similar number who had normal urinary albumin excretion rates. Macrovascular disease (ischaemic heart disease and peripheral vascular disease) was present in 10 patients with proteinuria but in only three with normal albumin excretion rates, and proliferative retinopathy was detected in 11 and four patients in the two groups. There was no significant excess of smokers in the group with proteinuria. Blood pressure was, however, higher in the patients with proteinuria--mean systolic pressure 161 (SD 18) mm Hg compared with 135 (19) mm Hg (95% confidence interval of difference between means 15 to 38 mm Hg); mean diastolic pressure 90 (SD 12) mm Hg compared with 79 (15) mm Hg (confidence interval 3 to 19 mm Hg). The concentration of serum high density lipoprotein (HDL) cholesterol isolated by precipitation was lower in the patients with proteinuria (confidence interval 0.02 to 0.41 mmol/l). Their concentration of HDL2 cholesterol isolated by ultracentrifugation was also decreased (confidence interval 0.02 to 0.40 mmol/l), whereas HDL3 cholesterol tended to be increased (confidence interval -0.01 to 0.23 mmol/l). There was also a trend for serum cholesterol concentrations to be higher in the presence of proteinuria (confidence interval -0.39 to 1.20 mmol/l). The aggregation of risk factors for atherosclerosis in insulin dependent diabetes mellitus complicated by proteinuria helps to explain the increased prevalence of ischaemic heart disease and peripheral vascular disease reported in these patients. Early renal disease in insulin dependent diabetes may have an important role in hypertension and altered lipoprotein metabolism.