M. Hartog

EFFECT OF PECTIN ON SERUM LIPIDS AND LIPOPROTEINS, WHOLE-GUT TRANSIT-TIME, AND STOOL WEIGHT

Pectin (12g daily with meals) was taken by twelve healthy men aged 22-45 (mean 25 yr) for 3 weeks. This produced a statistically significant mean decrease in total serum-cholesterol of 0.48 +/- 0.18 mmol/1 (+/- S.E.M.)--i.e., 7.9 +/- 2.6%. The decrease was largely due to a reduction in serum-low-density-lipoprotein-cholesterol of 0.45 +/- 0.19 mmol/1 accompanied by a fall in serum-apolipoprotein-B of 0.11 +/- 0.04 g/1. During pectin administration wet stool weight increased from 150 +/- 10 to 186 +/- 15 g/24 h. There was no clear change in total serum-triglycerides, serum very low density lipoproteins, or in whole-gut transit-time.

A RADIOIMMUNOASSAY FOR CHOLECYSTOKININ-PANCREOZYMIN

A sensitive and specific radioimmunoassay for cholecystokinin-pancreozymin (CCK-PZ) has been developed, using rabbit antisera to crude porcine hormone. Highly purified porcine CCK-PZ, labelled with (131)I, and repurified by column chromatography on Sephadex G15, was used as tracer. Separation of free from antibody-bound labelled CCK-PZ was carried out using charcoal, ion-exchange resin, or a double antibody procedure. Non-specific interference with the assay system by serum factors was abolished (as judged by in-vitro and in-vivo recovery studies) by boiling and diluting the serum samples before assay. Ninety-nine per cent pure porcine CCK-PZ (standard), commercial CCK-PZ preparations, caerulein, the C-terminal 8- and 12-amino acid fragments of the CCK-PZ molecule, and endogenous human CCK-PZ all cross reacted in the assay system and showed parallel inhibition curves. No significant cross reaction was found with gastrin, secretin, glucagon, or insulin. The sensitivity of the assay is approximately 5 pg per ml of test solution, which proved adequate for measuring physiological levels of CCK-PZ in peripheral blood in man.The mean immunoreactive CCK-PZ concentration in 50 fasting normal subjects was 60.4 pg per ml. The distribution of individual values was skewed, however, so that the median was much lower (30 pg per ml). Older subjects had higher fasting levels of CCK-PZ than were found in young adults.

Serum and lipoprotein apolipoprotein B levels in normal subjects and patients with hyperlipoproteinaemia

Apolipoprotein B (apo B) levels were measured by radioimmunoassay in the serum and lipoproteins from normal subjects and patients with hyperlipoproteinaemia. The total serum apo B concentration in normal subjects was 0.91 +/- 0.16 g/l (mean +/- S.D.); in type IIa hyperlipoproteinaemia it was 2.24 +/- 0.61 g/l; in type IIb, 3.05 +/- 1.24 g/l; in type IV, 2.24 +/- 0.99 g/l; and in type V, 1.30 +/- 0.16 g/l. In normal subjects 5.6 +/- 2.1% (mean +/- S.D.) of total apo B was present in very low density lipoproteins (VLDL) and 93 +/- 9% in low density lipoproteins (LDL). Corresponding values for type IIa were 3.8 +/- 1.9% and 93 +/- 3%, for type IIb, 9.9 +/- 7.5% and 91 +/- 1%, for type IV, 16.9 +/- 9.5% and 81 +/- 9%, and for type V, 38.4 +/- 11.0% and 52 +/- 8%. The ratio of cholesterol to apo B in serum was decreased in types IIa, IIb and IV, and increased in type V whereas the ratio of triglyceride to apo B in serum was decreased in type IIa, normal in type IIb and increased in types IV and V. The ratio of cholesterol to apo B in VLDL was increased in types IIa, IIb and V, but normal in type IV, whereas in LDL, this ratio was normal in types IIa and V but reduced in types IIb and IV. The ratio of triglycerides to apo B in VLDL was normal in types IIa, IIb and IV but raised in type V. In LDL, this ratio was increased in types IIb and IV but normal in types IIa and V.

Radioimmunoassay of cholecystokinin-pancreozymin.

A sensitive and specific radioimmunoassay for cholecystokinin-pancreozymin (CCK-PZ) has been developed, using rabbit antisera to crude porcine hormone. Highly purified porcine CCK-PZ, labelled with 131I, and repurified by column chromatography on Sephadex G15, was used as tracer. Separation of free from antibody-bound labelled CCK-PZ was carried out using charcoal, ion-exchange resin, or a double antibody procedure. Non-specific interference with the assay system by serum factors was abolished (as judged by in-vitro and in-vivo recovery studies) by boiling and diluting the serum samples before assay. Ninety-nine per cent pure porcine CCK-PZ (standard), commercial CCK-PZ preparations, caerulein, the C-terminal 8- and 12-amino acid fragments of the CCK-PZ molecule, and endogenous human CCK-PZ all cross reacted in the assay system and showed parallel inhibition curves. No significant cross reaction was found with gastrin, secretin, glucagon, or insulin. The sensitivity of the assay is approximately 5 pg per ml of test solution, which proved adequate for measuring physiological levels of CCK-PZ in peripheral blood in man. The mean immunoreactive CCK-PZ concentration in 50 fasting normal subjects was 60·4 pg per ml. The distribution of individual values was skewed, however, so that the median was much lower (30 pg per ml). Older subjects had higher fasting levels of CCK-PZ than were found in young adults.

Change of insulin dosage, circulating free and bound insulin and insulin antibodies on transferring diabetics from conventional to highly purified porcine insulin.

SummaryFifty-eight patients on long term conventional mainly bovine insulins have been transferred to highly purified porcine insulin preparations. There was an overall reduction of 22% in daily insulin dosage and improved diabetic control as shown by decreased blood glucose concentration. Increased concentrations of serum free insulin and falls in serum bound insulin levels were also found. There were reductions in the serum binding capacities and affinity constants on changeover from conventional to highly purified insulin due to a combination of the effects of differential conventional/purified porcine binding and the substitution of a low antigenicity insulin. However, 12 of the patients receiving higher doses of insulin experienced marked hypoglycaemic reactions immediately on insulin change-over despite initial dosage reductions of 30% and prior to any changes in antibody characteristics.

The relationship between blood glycosylated haemoglobin and home capillary blood glucose levels in diabetics

SummarySerial capillary blood glucose levels from insulin treated patients were recorded over 24 hour periods at fortnightly intervals for three months. Total glycosylated haemoglobin as % of HbA was measured at the end of this period by the Flückiger method, and % HbA1 by column chromatography. There were highly significant correlations between mean blood glucose levels over the three months and % HbA1 (r=0.93, 95% confidence limits 0.84–0.98), and with total glycosylated haemoglobin (r=0.88, 95% confidence limits 0.75–0.94). There was also a good correlation between results obtained by the two methods (r=0.81, p<0.0001). There were less strong correlations between % HbA1 and blood glucose levels during each of the three months before the estimation, with percentage of glucose levels greater than 10 mmol/l and with mean fasting blood glucose. These data support the hypothesis that % HbA1 and total glycosylated haemoglobin are satisfactory measurements of short term diabetic control.

The effect of improvement in diabetic control on plasma and whole blood viscosity

SummaryRheological studies were made on the blood of 12 diabetic patients after a period of poor diabetic control (HbA1 12.6±0.7% (mean ± SD); mean home capillary blood glucose level 11.7±1.2 mmol/l), and after at least three months of improved control (HbA1 9.1±0.4%, p<0.01; mean home capillary blood glucose level 9.2±0.6 mmol/l). There were significant decreases in plasma fibrinogen levels (4.1±0.6 to 3.7±0.6 g/l, p <0.01), plasma viscosity (1.31±0.1 to 1.25±0.04, p<0.001), and whole blood viscosity at low (22.8±2.7 to 20.2±2.9, p<0.01) and high shear rates (3.4 ±0.2 to 3.1±0.2, p<0.01). Ten diabetics with clinically evident complications were matched with diabetics of similar age, sex, duration and current control of diabetes. There were no significant differnces in plasma or whole blood viscosities between the two groups. Hyperviscosity in diabetes seems strongly related to hyperglycaemia and to be influenced by the quality of diabetic control.

Serum free insulin concentrations during the treatment of diabetic coma and precoma with low dose intramuscular insulin

SummaryFifty patients in diabetic coma or precoma, 33 of whom had previously received insulin and had circulating insulin antibodies, were studied during treatment with a low-dose intramuscular insulin regime. In the presence of insulin antibodies, serum free insulin was separated from bound insulin by steady-state gel filtration. The initial mean serum free insulin concentration in the group of patients without insulin antibodies was 9 mU/l, 1 to 2 hours after intramuscular therapy it had risen to 22 mU/l, and after 7 to 8 hours to 73 mU/l. The corresponding concentrations for the group with insulin antibodies were 13, 23 and 74 mU/l. No relationship was found between the concentrations of serum free insulin attained and the age of the patients, their initial degree of acidosis, dehydration, and systolic blood pressure, the insulin antibody characteristics of their sera, nor the rate of decline of the blood glucose.

Relationship between changes of serum cholecystokinin-pancreozymin and serum insulin after different stimuli

SummaryThe relationship between changes of serum immuno-reactive cholecystokinin-pancreozymin (CCK-PZ) and serum immuno-reactive insulin has been studied after various stimuli. The oral administration of 5% glucose or magnesium sulphate and the intra-duodenal administration of olive oil were all followed by a rise of serum CCK-PZ. The serum insulin rose after 5% glucose and also showed a small but insignificant rise with olive oil. There was, however, no change of serum insulin after the ingestion of magnesium sulphate suggesting that CCK-PZ in isolation does not stimulate insulin release.

Does Simple Substitution of Fiber-Rich Foods for Refined Foods Aid in the Treatment of Diabetes Mellitus?

There is now considerable evidence that high-carbohydrate, high-fiber diets lead to improved diabetic control compared with conventional 40% carbohydrate diets (Kiehm et al., 1976; Anderson and Ward, 1978, 1979; Simpson et al., 1979a,o). However, it is not clear whether these diets achieve their beneficial effect through their high carbohydrate intake, their high fiber intake, or the fiber-rich nature of their carbohydrate, or, perhaps, through a combination of these properties.