Lars-Olof Almér

Elevated levels of the rapid inhibitor of plasminogen activator (t-PAI) in acute myocardial infarction

Myocardial infarction is frequently caused by acute coronary thrombosis. A previous study in patients three years after myocardial infarction has shown twice as high concentrations of the rapid inhibitor of plasminogen activator (t-PAI) as in healthy controls. The present study involves 29 patients with acute onset of myocardial infarction. Already on admission the mean concentration of t-PAI was 16.5 +/- 7.4 units/ml as compared to 7.5 +/- 2.3 in healthy controls. It is presently unknown if moderately elevated t-PAI levels contribute to a delay of the spontaneous thrombolysis of the coronary occlusion, thus promoting the development of myocardial infarction.

Abnormal diastolic blood pressure and heart rate reactions to tilting in diabetes mellitus

SummaryThe orthostatic reaction to tilting was studied in 46 diabetics without symptoms of autonomic neuropathy and in 31 age-matched healthy control subjects. After tilting, the diastolic blood pressure rose in the control subjects but was unchanged or tended to fall in the diabetics, except in those of short duration without retinopathy. After tilting, the control subjects showed an immediate increase in heart rate with the highest value at 8.4±1.0 s (mean±SEM), followed by a transient decrease with lowest value at 21.2±0.9 s. The acceleration and brake index measured the changes in heart rate. The brake index was lower in diabetics of short duration with retinopathy (6.9±1.6) than in those without (14.4±2.3, p <0.01) as well as matched control subjects (18.7±2.5, p < 0.01). In the diabetics of long duration no differences were shown between those with or without retinopathy but the acceleration (10.3±1.6 vs 19.9±2.3, p < 0.05) and the brake index (5.3±1.4 vs 19.9±2.3, p < 0.01) were lower in those with vagal neuropathy.

Measurement of gastric emptying by standardized real-time ultrasonography in healthy subjects and diabetic patients.

The aim of this study was to simplify and standardize a reproducible, well‐tolerated and clinically applicable method for the assessment of gastric emptying rate by real‐time ultrasonography. A total of 33 subjects were examined, including 19 healthy subjects and 14 patients with insulin‐dependent diabetes mellitus and clinically suspected delayed gastric emptying. Measurements of the gastric antrum were taken in the supine position and in relation to internal landmarks to obtain a standardized cross‐sectional image producing the area of a selected slice of the antrum. Diabetic patients were examined on the condition that the fasting blood glucose level was 3.5 to 9.0 mmol/l. Gastric emptying rate was estimated and expressed as the percentage reduction in antral cross‐sectional area from 15 to 90 min after the ingestion of a standardized semisolid breakfast meal (300 g rice pudding, 330 kcal). Interobserver and intraobserver measurement errors were assessed, as was the significance of age and sex on gastric emptying. In comparison to healthy subjects, diabetic patients showed significantly wider median values of the 90 min postprandial antral area, but only a mild tendency toward greater dilation of the gastric antrum prior to and 15 min after meal ingestion. The median value of gastric emptying rate in these diabetic patients was estimated at 29%, which was less than half of that in the healthy subjects (63%). Statistically the difference was highly significant. Interpersonal variability of gastric emptying rate and antral areas was large for both groups. Measurements of gastric emptying rate gave highly reproducible results on separate days and from different observers (interobserver systematic measurement error 0.3% and random measurement error 10.9%; intraobserver systematic measurement error 3.6% and random measurement error 9.5%). No difference in gastric emptying rate was found related to age or sex. We conclude that the use of standardized real‐time ultrasonography to determine gastric antral cross‐sectional area in a single section of the stomach is a valid method for estimating gastric emptying rate.

Effects of 1 and 3 g cinnamon on gastric emptying, satiety, and postprandial blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and ghrelin concentrations in healthy subjects

BACKGROUND A previous study of healthy subjects showed that intake of 6 g cinnamon with rice pudding reduced postprandial blood glucose and the gastric emptying rate (GER) without affecting satiety. OBJECTIVE The objective was to study the effect of 1 and 3 g cinnamon on GER, postprandial blood glucose, plasma concentrations of insulin and incretin hormones [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1)], the ghrelin response, and satiety in healthy subjects. DESIGN GER was measured by using real-time ultrasonography after ingestion of rice pudding with and without 1 or 3 g cinnamon. Fifteen healthy subjects were assessed in a crossover trial. RESULTS The addition of 1 or 3 g cinnamon had no significant effect on GER, satiety, glucose, GIP, or the ghrelin response. The insulin response at 60 min and the area under the curve (AUC) at 120 min were significantly lower after ingestion of rice pudding with 3 g cinnamon (P = 0.05 and P = 0.036, respectively, after Bonferroni correction). The change in GLP-1 response (DeltaAUC) and the change in the maximum concentration (DeltaC(max)) were both significantly higher after ingestion of rice pudding with 3 g cinnamon (P = 0.0082 and P = 0.0138, respectively, after Bonferroni correction). CONCLUSIONS Ingestion of 3 g cinnamon reduced postprandial serum insulin and increased GLP-1 concentrations without significantly affecting blood glucose, GIP, the ghrelin concentration, satiety, or GER in healthy subjects. The results indicate a relation between the amount of cinnamon consumed and the decrease in insulin concentration.

Low vascular fibrinolytic activity in obesity.

Abstract The blood fibrinolytic activity is abnormally low in obesity. A significant correlation was found between the endothelial content of plasminogen activator in the vessel walls and degree of overweight. It is suggested that this impairment of fibrinolysis might contribute to the high incidence of vascular complications in obesity.

Diabetic Retinopathy and the Fibrinolytic System

We found that patients with long-standing (>10 years) diabetes who have not developed retinopathy had a significantly higher and almost normal fibrinolytic response to venous occlusion and also a higher spontaneous fibrinolytic activity than those who had developed retinopathy. In the latter, the low fibrinolytic activity of the blood was, however, not correlated to a low plasminogen activator activity of the vessel walls. Although generally lower than in controls, the activator activity of the vessel walls in the retinopathy group tended to be higher than in the rest, and in fact those with only minor vascular changes (microaneurysms) had a significantly higher activity than the other diabetics. The fibrinogen and alpha2-macroglobulin levels were higher in the retinopathy group. Thus multiple abnormalities of the fibrinolytic system were found to be related to diabetic microangiopathy.

Capillary Blood on Filter Paper for Determination of HbA1c by Ion Exchange Chromatography

OBJECTIVE To facilitate HbA1c determination, we evaluated an HbA1c filter paper system enabling capillary blood sampling at home by the patients. RESEARCH DESIGN AND METHODS Capillary blood (two drops) was applied to a filter paper (HbA1c Via Post) and sent to the laboratory where a small disc was punched out on the filter paper. Hemoglobin was eluted from the disc in a buffer containing cysteine to eliminate the interfering glutathione adduct (HbA3) formed during storage. Analysis was performed by ion-exchange chromatography (Mono S, high-performance liquid chromatography), and the eluate was compared with hemolysate of venous blood from 41 patients. The stability of blood impregnated on filter paper was checked at different temperatures over different periods of time. RESULTS There was an excellent agreement (r = 0.99) between HbA1c values from capillary blood on filter paper and HbA1c values from venous blood. HbA1c values were constant when stored on filter paper for 5–7 days at 20–21°C (room temperature) or at 4–6°C (refrigerator) for 10 days as well as at −70°C for several months after blood sampling. A new chromatographic-interfering hemoglobin fraction both from venous and capillary samples was identified as free alpha-chain of hemoglobin. CONCLUSIONS The HbA1c filter paper system enables capillary blood sampling at home, eliminates the need of vein puncture in children and adults, and provides the diabetologist with an HbA1c value when the patient visits the clinic without a need for a previsit phlebotomy.

INCREASED VON WILLEBRAND-ANTIHAEMOPHILIC FACTOR A IN DIABETIC RETINOPATHY

The von Willebrand factor‐Factor VIII (vW‐AHF) related protein and the AHF (antihaemophilic factor A) activity have been measured in the blood of 63 diabetic patients with and without diabetic retinopathy. Compared to normals, diabetic patients showed a clear increase in both vW‐AHF related protein and AHF activity. Patients with retinopathy had a level of vW‐AHF related protein significantly higher than patients without retinopathy. Since the von Willebrand factor is involved in the mechanism of platelet adhesion and aggregation these findings may contribute to an explanation of the increased platelet stickiness known to occur in diabetics and especially in those with retinal changes.

Effect of commercial breakfast fibre cereals compared with corn flakes on postprandial blood glucose, gastric emptying and satiety in healthy subjects: a randomized blinded crossover trial

BackgroundDietary fibre food intake is related to a reduced risk of developing diabetes mellitus. However, the mechanism of this effect is still not clear. The aim of this study was to evaluate the effect of commercial fibre cereals on the rate of gastric emptying, postprandial glucose response and satiety in healthy subjects.MethodsGastric emptying rate (GER) was measured by standardized real time ultrasonography. Twelve healthy subjects were assessed using a randomized crossover blinded trial. The subjects were examined after an 8 hour fast and after assessment of normal fasting blood glucose level. Satiety scores were estimated and blood glucose measurements were taken before and at 0, 20, 30, 40, 60, 80, 100 and 120 min after the end of the meal. GER was calculated as the percentage change in the antral cross-sectional area 15 and 90 min after ingestion of sour milk with corn flakes (GER1), cereal bran flakes (GER2) or wholemeal oat flakes (GER3).ResultsThe median value was, respectively, 42% for GER1, 33 % for GER2 and 51% for GER3. The difference between the GER after ingestion of bran flakes compared to wholemeal oat flakes was statistically significant (p = 0.023). The postprandial delta blood glucose level was statistically significantly lower at 40 min (p = 0.045) and 120 min (p = 0.023) after the cereal bran flakes meal. There was no statistical significance between the areas under the curve (AUCs) of the cereals as far as blood glucose and satiety were concerned.ConclusionThe result of this study demonstrates that the intake of either bran flakes or wholemeal oat flakes has no effect on the total postprandial blood glucose response or satiety when compared to corn flakes. However, the study does show that the intake of cereal bran flakes slows the GER when compared to oat flakes and corn flakes, probably due to a higher fibre content. Since these products do not differ in terms of glucose response and satiety on healthy subjects, they should be considered equivalent in this respect.Trial registrationISRCTN90535566

Correlation between simultaneous scintigraphic and ultrasonographic measurement of gastric emptying in patients with type 1 diabetes mellitus.

Objective. To compare scintigraphic measurements of total stomach emptying of a semisolid meal with ultrasonographic measurements of changes in antral area as estimates of antral emptying in type 1 diabetic patients. Methods. Eleven patients with insulin‐dependent diabetes mellitus were studied with simultaneous measurements of gastric emptying by scintigraphy and ultrasonography. Patients were imaged immediately after ingestion (time 0) and every 15 minutes over 120 minutes. The gastric emptying rate was expressed as percent reduction in antral cross‐sectional area from 15 to 90 minutes after meal ingestion. Results. Ultrasonographic measurements showed a postprandial maximal antral area at 15 minutes, continuously decreasing with time, and reaching a plateau 45 to 90 minutes after the end of meal ingestion, whereas the scintigraphic counts attained their maximum immediately after the meal and began to fall thereafter. Between 15 and 90 minutes, the residual radioactivity and antral ultrasonographically measured distension curves were concordant. The curves then showed a tendency toward deviation for the last 15 minutes (median, 51% versus 59% at 105 minutes and 40% versus 57% at 120 minutes, respectively). A strong significant correlation could be seen between the ultrasonographic gastric emptying rate and scintigraphic half‐time values (r = –0.94; P < .001). Comparing scintigraphic and ultrasonographic half‐time values showed a systematic measurement error of 9.9 minutes and a random measurement error of 18.6 minutes. Conclusions. The use of standardized real‐time ultrasonography to determine the gastric emptying rate of semisolid meals in diabetic patients, with the use of the change in gastric antral cross‐sectional area in a single section of the stomach 15 and 90 minutes postprandially, offers a valid method for clinical practice.