Measurements of the gastric emptying rate by use of ultrasonography: studies in humans using bread with added sodium propionate.

BACKGROUND: Foods with a low glycemic index are increasingly being acknowledged as beneficial for individuals with disorders related to the insulin resistance syndrome. The presence of certain salts of organic acids has been shown to lower the glycemic index of bread products and one of the suggested mechanisms is a lowered gastric emptying rate (GER). One obvious pitfall with many of the common techniques for GER measurement is that the food structure, and hence the gastric release of nutrients, may be affected by enclosure of the marker for gastric emptying, eg, paracetamol. Ultrasonography is a noninvasive method for which the above pitfall is to a large extent avoided. OBJECTIVE: The main objective was to evaluate the use of ultrasonography to determine whether the lowered glycemic and insulinemic responses to bread ingestion after the addition of sodium propionate are explained by a specific effect of propionate on the GER. DESIGN: The effect of sodium propionate in bread was evaluated in 9 healthy volunteers. Barley bread products, with or without added sodium propionate, were ingested as breakfast after an overnight fast. The GER was monitored for 2 h by ultrasonography; during this period, capillary blood was withdrawn repeatedly for measurement of blood glucose and insulin. RESULTS: The GER of the barley bread decreased markedly after the addition of sodium propionate and was accompanied by lowered glycemic and insulinemic responses. CONCLUSION: The lowered glycemic response to ingestion of bread with added sodium propionate appears to be related to a lowered GER.

Delayed gastric emptying rate in Type 1 diabetics with cardiac autonomic neuropathy.

Gastroparesis is a frequent complication of longstanding diabetes and has been attributed to vagal nerve dysfunction, occurring as part of a generalized autonomic neuropathy. We wanted to clarify the relationship between delayed gastric emptying (GE) and cardiac autonomic neuropathy (CAN) in type 1 diabetics. Using a standardized ultrasound technique, GE was studied in 20 type 1 diabetic patients with poor glycaemic control despite good compliance and 10 normal healthy volunteers (Group 1). Measurements of GE were done on condition that the fasting blood glucose was 3.5-9.0 mmol/l. Diabetic patients were classified into two groups according to the absence (Group 2) or presence (Group 3) of CAN, using the deep breathing test (E:I ratio) to evaluate parasympathetic vagal nerve function. Age-related reference values were used to evaluate the indices of CAN. The supine resting heart rate was also checked, and the patients were asked for symptoms of gastroparesis. The three groups were similar in terms of sex and smoking habits, and there was no significant difference regarding the age and body mass index (BMI). The mean duration of diabetes and the glycaemic control (HbA1c) was insignificant between patients in Groups 2 and 3. Diabetic patients in Group 3 showed lower gastric emptying rates (GER) than the healthy volunteers in Group 1 (median GER 16% vs. 63%, P<.01) and the patients in Group 2 (median GER 16% vs. 54%, P<.01). No significant difference in GER could be seen between patients in Group 2 and subjects in Group 1 (median GER 54% vs. 63%, P=.08). Assuming that GER<45% indicated a delayed GE, 8 of 10 patients in Group 3 had delayed GE compared to only 3 of 10 patients in Group 2. There were disagreements between symptoms of gastroparesis and delayed GE. We conclude that there is a significant lower GER in type 1 diabetic patients with CAN than in those without, unrelated to symptoms of gastroparesis.

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.

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 degrees C (room temperature) or at 4-6 degrees C (refrigerator) for 10 days as well as at -70 degrees 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.

Altered metabolism of acetaldehyde in blood is not a specific marker of diabetic macroangiopathy.

Previous studies have demonstrated altered acetaldehyde metabolism in diabetics with macroangiopathy. Elimination of acetaldehyde in blood homogenates was studied in 20 non-diabetic survivors of myocardial infarction and 22 healthy controls. The half-life of acetaldehyde was shorter in patients, than in controls (mean values 83 and 150 minutes, respectively, p less than 0.001). Thus, the presence of diabetes is not a prerequisite for altered acetaldehyde metabolism in angiopathy patients. Elimination of acetaldehyde proved to be an enzymatic process, as the elimination was virtually abolished in the presence of chloral hydrate, an inhibitor of aldehyde dehydrogenase. In a previous study, however, results of a more specific assay of aldehyde dehydrogenase showed no correlation to the half-life of acetaldehyde. A possible explanation of the rapid acetaldehyde elimination in angiopathy patients is a low capacity of blood proteins for acetaldehyde binding.

Absent elevations in growth hormone, factor VIII related antigen, and plasminogen activator activity during exercise in diabetic patients resistant to retinopathy.

In cross-sectional studies elevations in growth hormone (GH), factor VIII related antigen (VIIIR:Ag), and plasminogen activator activity (PAA) have been connected with diabetic retinopathy. To evaluate the importance of these factors for the development of retinopathy, we have carried out a prospective study. In a primary study GH, VIIIR:Ag, and PAA were evaluated during a 25 min exercise test in 22 insulin dependent diabetes mellitus (IDDM) patients. After 5-7 years, the patients were re-evaluated and the presence of retinopathy in the follow-up study was correlated to the findings in the primary study. Patients with retinopathy in the primary or the second study (n = 14) showed a significant increase in GH (p less than 0.05) during the first 5 min of exercise compared with patients without retinopathy. Moreover, the 14 retinopathy patients showed further significant elevations in GH (p less than 0.001), VIIIR:Ag (p less than 0.01) and PAA (p less than 0.001) during the remaining 20 min of exercise. In contrast, patients without retinopathy (n = 8) in the follow-up study, did not show significant elevations in GH, VIIIR:Ag, and PAA during exercise. A lack of rise in GH, VIIIR:Ag, and PAA during exercise seems to indicate a resistance to retinopathy in IDDM patients.

Aldehyde dehydrogenase activity and vascular disease in type II diabetes--a comparison between 2 different assays for activity.

We have recently reported that type II diabetic subjects with macroangiopathy have a higher activity of aldehyde dehydrogenase (ALDH) in blood than those without clinical vascular disease. ALDH activity was measured as the elimination of acetaldehyde added to a blood homogenate in vitro. We have re-examined our clinical material with another assay of ALDH which uses indole-3-acetaldehyde as substrate and measures the formation of indole-3-acetic acid. A negative correlation between the half-life of acetaldehyde and the formation of indole-3-acetic acid was found in the group of subjects free from vascular disease (r = -0.55, p less than 0.01). Thus, a rapid elimination of acetaldehyde corresponded to a rapid formation of indole-3-acetic acid. No such correlation was found in subjects with macroangiopathy. These results suggest that the 2 groups, with and without clinical vascular disease, have differences in isoenzyme composition, in the kinetic properties of the enzyme, or in the non-enzymatic binding of acetaldehyde.

Motilin response to a glucose load aberrant in smokers.

Smoking is known to influence the blood glucose response to an oral glucose load, possibly by altering the gut motility. Because the peptide hormone motilin might be involved in the regulation of the gastric emptying pattern, we studied 12 heavy smokers and 9 non-smokers after an overnight fast and tobacco abstinence. After an oral glucose load non-smokers showed falling serum motilin levels, as expected, whereas the smokers had initially increasing values. We conclude that smoking affects the gastrointestinal tract, not only during acute nicotine exposure but also chronically.

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.

Effects of chlorpropamide and alcohol on aldehyde dehydrogenase activity and blood acetaldehyde concentration.

Aldehyde dehydrogenase (ALDH) activity is increased in Type 2 diabetics with macrovascular disease, and is a critical factor determining the chlorpropamide-alcohol flush (CPAF), a phenomenon possibly related to diabetic complications. To evaluate the possible effects of chlorpropamide (CP) on ALDH activity we studied 8 Type 1 and 20 Type 2 diabetics. Blood acetaldehyde concentration after intake of CP and alcohol was higher in patients with CPAF than in those without CPAF (p less than 0.005), and in those with low basal erythrocyte ALDH activity than in those with high basal enzyme activity (p less than 0.05). Administration of CP reduced ALDH activity in 20 of 26 patients (p less than 0.05). Alcohol intake was observed to have an additional inhibitory effect on ALDH activity. Accordingly, a combination of CP and alcohol decreases the activity of erythrocyte ALDH which might explain the CPAF phenomenon. Absent correlation between CP level and reduction of ALDH activity indicates a major role for alcohol in CPAF. A therapeutic dose of CP or a small amount of alcohol might be used when a reduction of ALDH activity is considered.

The fibrinolytic system and coagulation during bezafibrate treatment of hypertriglyceridemia.

Bezafibrate was given to 23 hypertriglyceridemic but otherwise healthy middle-aged men in a double-blind, cross-over study to evaluate its effect on the components of the fibrinolytic system as well as on ATIII, FVIIIR: Ag, FVIII: C and platelet aggregation. Fibrinogen dropped markedly (P less than 0.05) and there was a small but significant fall of ATIII. The second wave of platelet aggregation was found much less frequently than in controls (P less than 0.001). Bezafibrate seemed to decrease the rate of formation of the first wave platelet aggregation.

Aldehyde dehydrogenase activity and large vessel disease in diabetes mellitus. A preliminary study.

Type II diabetic subjects, 26 with symptoms and/or signs of large vessel disease (LVD group) and 26 free from clinical vascular disease (FVD group), matched for sex, age, body weight, and duration of diabetes after diagnosis, together with 28 healthy controls participated in a preliminary study on new potential risk factors of large vessel disease. The activity of erythrocyte aldehyde dehydrogenase (ALDH) was significantly higher (P less than 0.005) in the LVD than in the FVD group and in the controls, as indicated by a shorter half-life of acetaldehyde in homogenates of erythrocytes and plasma (100 +/- 11, 203 +/- 28, and 180 +/- 21 min, respectively). The results were unaffected by antidiabetes therapy, blood glucose control, alcohol consumption, or by recognized risk factors of angiopathy, such as blood pressure, hyperlipidemia, or smoking. Whether ALDH activity is a primary factor in large vessel disease or is merely a secondary phenomenon is unknown. However, ALDH activity is a critical factor determining chlorpropamide alcohol flush (CPAF), which has been suggested to be an inherited trait in some type II diabetic subjects. In conclusion, high ALDH activity was shown to be associated with an increased risk of large vessel disease in diabetes.

Autonomic neuropathy and toe circulation. A prospective study.

Ankle and toe pressure ratios and toe temperature reactions to cold followed by indirect heating were evaluated in 23 diabetic patients with and without autonomic neuropathy (AN) in a first and in a second follow-up study after 5-7 years. In the first study, despite normal blood pressure ratios, AN patients, all with parasympathetic neuropathy, showed a markedly delayed increase in toe temperature after cooling followed by indirect heating. In the second study, most AN patients showed sympathetic neuropathy and had higher toe temperatures before cooling than those without AN. Parasympathetic neuropathy leads to increased sensitivity to cold in toe vessels and sympathetic neuropathy to vasodilation and increased toe temperatures.

A prospective study of the immunogenicity of porcine insulin in HLA-typed new insulin-treated diabetics.

Fifty-four diabetics were started on insulin therapy with highly purified porcine insulin (Velosulin, Insulatard, Mixtard) and treated for at least 1 yr with blood samples drawn at regular intervals for insulin antibody determinations. In 43 patients the insulin antibody response was correlated with HLA A, B, and DR antigens. Approximately half of the patients formed insulin antibodies within 6 months of treatment, and this incidence remained constant for up till 2 yr. In those patients who developed insulin antibodies a plateau of 12% insulin binding capacity was reached after 9-12 months which remained constant for up till 2 yr. Formation of antibodies to proinsulin and pancreatic polypeptide proved completely avoidable, and no local reactions at the injection sites were observed. There was indication of a positive association between HLA DR4 tissue types and the tendency to immune response to injected insulin (p = 0.07).

A case of brucellosis complicated by endocarditis and disseminated intravascular coagulation.

Brucellosis, being eradicated among domestic animals in some countries, is still prevalent in some others where it poses a potential threat to the consumers of milk and cheese and those working with animals and meat. The patient presented below had contracted a severe and long-standing Brucella abortus infection by ingesting raw camel milk. She had signs of endocarditis and disseminated intravascular coagulation, but recovered when treated with tetracyclin and streptomycin.

On plasma chlorpropamide, body weight and sex difference in chlorpropamide alcohol flush (CPAF).

There is evidence that the plasma chlorpropamide (CP) concentration is an important determinant of the chlorpropamide alcohol flush (CPAF). In 74 type 2 diabetics a highly significant correlation (r = 0.51, p less than 0.001) was present between the levels of plasma CP and the appearance of CPAF, measured as an index (the sum of the increase of the skin temperature and one-fourth of plasma acetaldehyde increase). Lower or no correlations were found when different threshold levels were considered. Body weight was significantly (p less than 0.001) inversely correlated to plasma chlorpropamide levels, which resulted in higher CP levels in females (mean body weight 68.6 kg, CP concentration 34.4 mg/l) than in males (83.4 kg, 26.0 mg/l), which explains the female preponderance among flushers.