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Biomedical subjects

K Hermansen

Publications and source records attributed to K Hermansen.

At least 19 recordsLinked to original sources

The day-to-day variation in insulin sensitivity in non-insulin-dependent diabetes mellitus patients assessed by the hyperinsulinemic-euglycemic clamp method.

The objective was to study the day-to-day variation in insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) and to analyze within- and between-person variances in the glucose infusion rate during steady state (M value). Ten NIDDM patients attending the outpatient clinic at Aarhus Amtssygehus were studied three times under standardized conditions. Each time, a 120-minute hyperinsulinemic-euglycemic clamp was performed. Similar M values were found on the 3 study days, with difference between M values on the 3 days of (mean +/- SD) 0.3 +/- 1.8 mg glucose/kg lean body mass (LBM)/min. The total coefficient of variation (CV) for M values was 57% after the first clamp, 55% after the second, and 53% after the third. Ninety percent of the total day-to-day variation in M values could be ascribed to between-person variation and 10% to within-person variation. Within-person components of variance included all sources of variation other than between-person variation. The within-person CV for M values was 11.9% +/- 7.2% after two clamp studies and 12.1% +/- 7.3% after three (P < .55). In conclusion, under standardized conditions, a valid estimate of insulin sensitivity assessed by the hyperinsulinemic-euglycemic clamp in NIDDM patients is obtained after a single measurement. Because of large between-person variation, paired data should be used when comparing insulin sensitivity in NIDDM patients.

Blood Glucose

Endothelin-1 stimulates insulin secretion by direct action on the islets of Langerhans in mice.

Endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor peptide, is secreted in response to insulin. Elevated circulating ET-1 levels have been found in patients with diabetes mellitus and vascular dysfunction. The question arises whether ET-1 acts as a direct modulator of insulin secretion. To test this, we studied the effects of ET-1 on isolated mouse islets of Langerhans. ET-1 (1 nmol/l-1 mumol/l) dose-dependently stimulated insulin secretion from islets incubated in the presence of 16.7 mmol/l glucose (p < 0.05). The effect of ET-1 is glucose-dependent since no potentiation was found at 3.3 mmol/l glucose. Furthermore, ET-1 induced a large, transient increase in glucose-stimulated insulin secretion during islet perifusion in the presence (p < 0.001), but not in the absence, of extracellular Ca2+. The rate of 45Ca(2+)-efflux from 45Ca(2+)-prelabelled islets was transiently stimulated by ET-1 during perifusion at 16.7 mmol/l glucose in the presence of extracellular Ca2+ (p < 0.001). A short-lived increase in 45Ca(2+)-efflux was also observed in the absence of extracellular Ca2+ (p < 0.05). It is suggested that the effects of ET-1 on insulin secretion are critically dependent on influx via Ca(2+)-channels. In addition, ET-1 transiently enhanced 86Rb(+)-efflux from 86Rb(+)-prelabelled islets both in the presence (p < 0.001) and in the absence (p < 0.001) of extracellular Ca2+ suggesting that ET-1 does not elicit insulin secretion by inhibition of the potassium permeability. Our study provides evidence that ET-1 stimulates insulin secretion via a direct effect on the islets of Langerhans.

Analysis of Variance

Stimulation of somatostatin secretion by 3-O-methylglucose in the perfused dog pancreas.

CONCLUSION: 3-O-methylglucose stimulates somatostatin secretion from the dog pancreas by a glucose-dependent and glucose-like effect. Therefore, it is possible that 3-O-methylglucose-stimulated somatostatin secretion is dependent on glucose metabolism. BACKGROUND: Somatostatin secretion from the endocrine pancreas is stimulated by glucose, glyceraldehyde, and dihydroxyacetone but not affected by fructose, galactose, or ribose. Whether the nonmetabolizable glucose analog, 3-O-methylglucose affects somatostatin secretion is, however, not known. METHOD: We therefore, examined whether the glucose analog affects somatostatin secretion in the perfused dog pancreas. RESULTS: We found that when added to a medium containing 2.7 mM or 5.5 mM D-glucose, 3-O-methylglucose (10 mM) stimulated somatostatin secretion to the same extent as did an equivalent dose of D-glucose. The same stimulation was observed also with arginine at 2.5 mM in the perfusion medium. In contrast, 3-O-methylglucose did not stimulate somatostatin secretion in the absence of glucose in the perfusion medium. Mannoheptulose (5 mM), which inhibits glucose metabolism, completely blocked the secretion to both hexoses.

3-O-Methylglucose

The acute impact of ethanol on glucose, insulin, triacylglycerol,and free fatty acid responses and insulin sensitivity in type 2 diabetes.

The aim of the present study was to evaluate the acute effect of ethanol on insulin sensitivity, and glucose, insulin, free fatty acid (FFA), and triacylglycerol responses in ten patients with non-insulin-dependent (type 2) diabetes. In the test study an oral dose of 0.66 g ethanol/kg followed by continuous intravenous infusion of 0.1 g ethanol/kg per h was given to maintain a constant ethanol level in the blood. In the control study identical volumes of oral water and intravenous saline (9 g NaCl/l) were given. After 90 min insulin sensitivity was determined by the hyperinsulinaemic, euglycaemic clamp technique. Ethanol caused no change in blood glucose or insulin concentrations. The FFA level was suppressed by ethanol while the triacylglycerol level was unaffected. The insulin sensitivity was not affected by ethanol. No major acute effect of ethanol on the glycaemic control in fasting type 2 diabetic patients was found in comparison with what is seen in healthy people. The present study, along with the sparse literature, indicates that the ability of ethanol to induce hypoglycaemia is attenuated or absent in diet-treated type 2 diabetes. Furthermore, we found no change in insulin sensitivity. Consequently, the risk of acute ethanol-induced aberrations in carbohydrate metabolism in diet-treated type 2 diabetes seems to be less than previously expected, when alcohol is not taken as a part of a meal.

Administration, Oral

Differential effects of saturated and monounsaturated fat on blood glucose and insulin responses in subjects with non-insulin-dependent diabetes mellitus.

To compare the metabolic effect of coingestion of saturated and monounsaturated fats with potato, 12 subjects with non-insulin-dependent diabetes mellitus (NIDDM) received 300 g mashed potato alone or in combination with 40 g olive oil, 80 g olive oil, 50 g butter, or 100 g butter, respectively. The blood glucose response area to potatoes with 100 g butter (448 +/- 68 mmol.240 min/L) was significantly lower than after the four other meals: 596 +/- 63 (potato alone), 649 +/- 82 (potato + 40 g olive oil), 587 +/- 80 (potato + 50 g butter), and 604 +/- 81 (potato + 80 g olive oil) nmol.240 min/L, P < 0.05, respectively. The insulin response was significantly increased by adding 50 and 100 g butter, whereas addition of 40 and 80 g olive oil had no effect. The fatty acid concentration was higher when 100 g butter was added to the potato meal than when it was not (0.67 +/- 0.05 compared with 0.48 +/- 0.07 mmol/L, P < 0.05). Fatty acid concentrations were similar to those found for the other meals. The triacylglycerol response increased in a dose-dependent manner with the fat content of the meals irrespective of the type of fat. We conclude that butter increases the insulin response more than does olive oil, and large amounts of butter also increase fatty acid and triacylglycerol concentrations.

Adult

Influence of parboiling and physico-chemical characteristics of rice on the glycaemic index in non-insulin-dependent diabetic subjects.

OBJECTIVE: To study the influence of parboiling, amylose content and gelatinisation temperature of rice on the postprandial blood glucose and insulin responses in non-insulin-dependent diabetic (NIDDM) subjects. DESIGN AND SUBJECTS: Twelve NIDDM subjects ingested high (27%) and low amylose content five test meals of 50 g available carbohydrates as white bread, cooked polished rice with high (27%) and low amylose content (12%) with different gelatinisation temperature and as nonparboiled and parboiled. The meals were taken in random order after a 12h fast with approximately 7 days interval. RESULTS: The glycaemic indices (GI) of all rice varieties were lower than that of white bread (P <0.001). Furthermore, GI of parboiled rice with a high amylose content was lower than that of parboiled rice with a low amylose content (50 +/- 7 vs 73 +/- 7, P <0.01). No differences were 47 +/- 4, n.s.), nor between non-parboiled and parboiled rice (50 +/- 7 vs 53 +/- 7, n.s.). Insulin responses to the five test meals were not significantly different in the NIDDM subjects. CONCLUSIONS: In NIDDM subjects the investigated rices were all low glycaemic as compared to white bread,independent of parboiling and physico-chemical characteristics. The mildparboiling process used did not influence GI. The study showed that the amylose content, but not the gelatinisation temperature, may be an useful criterion in selection of low GI rices also after parboiling.

Aged

Effects of galanin on proinsulin mRNA and insulin biosynthesis in normal islets.

Whether the potent insulinostatic neuropeptide galanin also inhibits insulin production in normal islets is not known. Therefore, isolated mouse islets were incubated for 90 min in 2.8 or 16.7 mmol/l glucose and 3H-labelled leucine with addition of mouse galanin at 1, 10 or 100 nmol/l. Galanin potently inhibited glucose-stimulated insulin secretion at both 10 and 100 nmol/l (P < 0.05), and proinsulin biosynthesis was slightly inhibited at 100 nmol/l (P < 0.05). Also, mouse islets were incubated for 48 h at 5 or 16.7 mmol/l glucose with galanin at 1, 10 or 100 nmol/l and proinsulin mRNA was determined by hybridisation of extracted RNA with digoxigenin-labelled oligonucleotide insulin probe. Proinsulin mRNA levels were approximately doubled by glucose at 16.7 mmol/l compared at 5 mmol/l (P < 0.05). Galanin did not affect islet proinsulin mRNA levels. Therefore, galanin seems to mainly regulate insulin secretion without any important role in the regulation of insulin availability in normal islets.

Animals

[Favourable effect of olive oil in patients with non-insulin-dependent diabetes. The effect on blood pressure, blood glucose and lipid levels of a high-fat diet rich in monounsaturated fat compared with a carbohydrate-rich diet].

To compare blood pressure, glucose and fat metabolism after a high-fat diet rich in monounsaturated fat reduced day time systolic (131 +/- 3 vs. 137 +/- 3 mmHg, p < 0.04) and 24-hour systolic blood pressure (126 +/- 8 vs. 130 +/- 10 mmHg, p < 0.03) as well as day time diastolic (78 +/- 2 vs. 84 +/- 52 mmHg, p < 0.02) and diurnal diastolic blood pressure (75 +/- 6 vs. 78 +/- 5 mmHg, p < 0.03) as compared with the high-carbohydrate diet. Evidence of improved glucose tolerance on the high-monounsaturated diet compared with the high-carbohydrate diet were found with lower fasting blood glucose (6.1 +/- 0.3 vs. 6.8 +/- 0.5 mM, p < 0.05), lower average blood glucose levels (7.4 +/- 0.5 vs. 8.2 +/- 0.6 mmol/l, p < 0.01) and peak blood glucose responses (9.9 +/- 0.6 vs. 11.3 +/- 0.7 mmol/l, p < 0.02). Similar levels of fasting triglyceride, total cholesterol, LDL- and HDL cholesterol were found after the two diets.

Blood Glucose

Plasma levels of von Willebrand factor in non-insulin-dependent diabetes mellitus are influenced by dietary monounsaturated fatty acids.

We have previously demonstrated a lowering effect on von Willebrand Factor (vWF) of a diet rich in monounsaturated fatty acids (MUFA) as compared with a high-carbohydrate diet. In the present study 16 non-insulin dependent diabetic (NIDDM) subjects participated in a cross-over experiment on an out-patient basis comparing the effects on vWF of three weeks treatments with two diets similar in carbohydrate and protein content, one rich in MUFA (30 energy %) and one rich in polyunsaturated fatty acids (PUFA) (30 energy %). Before and on the last day of the two diets, the levels of vWF, fibrinogen, fibronectin and alpha 2-macroglobulin were measured. After 3 weeks diet intervention vWF levels were lower after the MUFA regimen compared with the PUFA diet (mean +/- SD) (1.15 +/- 0.36 vs 1.32 +/- 0.42 U/ml, p = 0.003). Similar and unchanged levels of fibrinogen, fibronectin and alpha 2-macroglobulin were seen. In conclusion, three weeks on a diet rich in MUFA lowers vWF as compared with a PUFA rich diet, suggesting a beneficial effect of MUFA on the endothelium in NIDDM patients.

Cross-Over Studies

Urinary albumin excretion rate and 24-h ambulatory blood pressure in NIDDM with microalbuminuria: effects of a monounsaturated-enriched diet.

Previous studies have shown that unsaturated fat-enriched diets may have a beneficial effect on blood pressure in non-insulin-dependent diabetic (NIDDM) patients, whereas little is known about the effects on albuminuria. In a 3-week cross-over design we compared the effects of a currently recommended high-carbohydrate diet (50% carbohydrate, 30% fat [10% monounsaturated fat]) vs a diet rich in monounsaturated fat (30% carbohydrate, 50% fat [30% monounsaturated fat]) on urinary albumin excretion rate, 24-h ambulatory blood pressure and metabolic control in ten NIDDM patients with persistent microalbuminuria. The 24-h ambulatory blood pressure was similar before and after both the high-carbohydrate diet (mean +/- SD: 145/78 +/- 25/10 vs 143/79 +/- 19/10 mmHg (NS) and the monounsaturated fat diet: 140/78 +/- 16/8 vs 143/79 +/- 15/8 mmHg (NS). No changes were observed in day or night-time blood pressures. Urinary albumin excretion rate was unaffected after 3 weeks' treatment by the diets: from (geometric mean x/divided by tolerance factor) 32.4 x/divided by 2.1 to 36.0 x/divided by 1.9 micrograms/min (NS) vs from 34.2 x/divided by 1.9 to 32.1 x/divided by 2.1 micrograms/min (NS). Fasting plasma glucose, serum fructosamine and HbA1c as well as lipid and lipoprotein concentrations were stable during both diets. Compared to the high-carbohydrate diet a reduction in the LDL/HDL cholesterol ratio was observed during the monounsaturated fat diet (p < 0.03). In conclusion, compared to a high-carbohydrate diet, 3 weeks' treatment with a monounsaturated fat diet did not affect the levels of 24-h ambulatory blood pressure or albuminuria in microalbuminuric NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Comparison of the effects on the diurnal blood pressure, glucose, and lipid levels of a diet rich in monounsaturated fatty acids with a diet rich in polyunsaturated fatty acids in type 2 diabetic subjects.

The influence on blood pressure, glucose metabolism, and lipid levels of an exchange of polyunsaturated fatty acids with monounsaturated fatty acids in the diet was compared in 16 Type 2 diabetic outpatients. In a cross-over study design the patients were randomly assigned to 3 weeks treatments with a diet containing 30% energy as monounsaturated fatty acids, or an isoenergetic diet with 30% energy as polyunsaturated fatty acids. The contents of total fat, saturated fatty acids, cholesterol, and fibre were similar in the two diets. On the last days of the two diet periods, 24-h ambulatory blood pressure was measured and the responses of glucose, hormones, and lipids to a carbohydrate rich test meal were measured. As compared with the polyunsaturated fatty acids diet, the monounsaturated fatty acids diet reduced 24-h systolic (129 +/- 11 vs 124 +/- 8 mmHg (mean +/- SD), p = 0.02) and diastolic blood pressure (76 +/- 11 vs 73 +/- 8 mmHg, p = 0.02). The two diets had similar, beneficial effects on glycaemic control, and cholesterol and lipoprotein concentrations. A diet rich in monounsaturated fatty acids has beneficial effects on the blood pressure, while similar effects on glucose and lipid levels are observed in normotensive Type 2 diabetic subjects.

Blood Glucose

Early recognition of autonomic dysfunction in microalbuminuria: significance for cardiovascular mortality in diabetes mellitus?

The appearance of microalbuminuria in diabetic patients predicts development of macroalbuminuria and coronary heart disease. Autonomic dysfunction in ischaemic heart disease is related to an increased incidence of arrhythmic deaths. To assess sympathovagal balance in relation to microalbuminuria we performed 24-h spectral analysis of RR interval oscillations in 37 insulin-dependent diabetic patients. Patients were divided according to urinary albumin excretion as normo-(< 20 micrograms/min) (n = 12), micro-(> 20 and < 200 micrograms/min) (n = 14) and macro-albuminuria (> 200 micrograms/min) (n = 11). None had symptoms or signs of ischaemic heart disease at clinical examination or during stress testing. Fourteen matched healthy subjects served as controls. Overall RR interval variability was calculated as the 24-h standard deviation. The square root of power of the low-frequency (0.04-0.15 Hz) and high-frequency (0.15-0.40 Hz) component were considered indices of the sympathovagal interaction and vagal function, respectively. Patients with micro and macroalbuminuria had, compared to control subjects, significantly reduced 24-h standard deviation, a much smaller day/night difference in mean RR level and a significantly reduced amplitude of the low frequency and high frequency oscillations, which were even more reduced in macroalbuminuria. The differences in vagal function were also present after correction for mean RR level, and differences in physical training level and smoking. Insulin-dependent diabetic patients who develop microalbuminuria have significantly impaired vagal function and abnormal sympathovagal interaction, which is further deranged in macroalbuminuria. This early autonomic dysfunction may later contribute to a increased risk for sudden cardiac death.

Adult

Decrease in von Willebrand factor levels after a high-monounsaturated-fat diet in non-insulin-dependent diabetic subjects.

High levels of von Willebrand factor (vWF) have been reported in diabetics with vascular complications, suggesting a role for this protein in the development of cardiovascular complications in non-insulin-dependent diabetes mellitus (NIDDM). Recently, a diet rich in monounsaturated fatty acids (MUFA) has been found to improve glycemic control and decrease diurnal blood pressure as compared with a high-carbohydrate (H-CHO) diet in NIDDM subjects. To study the impact of MUFA on the hemostatic system, we compared the levels of vWF, fibrinogen, fibronectin, and alpha 2-macroglobulin before and after 3 weeks on a high-MUFA (H-MUFA) diet and on an isocaloric H-CHO diet in 15 NIDDM subjects. In a crossover study, the patients were randomly assigned to a H-CHO diet (50% carbohydrate, 30% fat [10% MUFA]) or a H-MUFA diet (30% carbohydrate, 50% fat [30% MUFA]). Before and on the last day of the two diets, vWF, fibrinogen, fibronectin, and alpha 2-macroglobulin levels were measured. The H-MUFA diet caused a decrease in vWF from 1.31 +/- 0.08 to 1.13 +/- 0.08 U/mL (P < .004), whereas an unchanged level was observed after a H-CHO diet (1.19 +/- 0.11 v 1.25 +/- 0.11 U/mL, NS). The relative changes in vWF during 3 weeks on a H-MUFA and on a H-CHO diet attained -12.5% +/- 3.2% versus 5.7% +/- 3.5%, respectively (P < .0001). Furthermore, unchanged levels of fibrinogen, fibronectin, and alpha 2-macroglobulin were seen after usage of the two diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-Over Studies

Effect of alcohol on glucose, insulin, free fatty acid and triacylglycerol responses to a light meal in non-insulin-dependent diabetic subjects.

Alcohol accounts for 4-6% of the average energy intake in most Western countries. Alcohol-induced hypoglycaemia is a well-known and feared complication in insulin-dependent diabetic subjects, but little attention has been paid to the impact of alcohol on carbohydrate metabolism in non-insulin-dependent diabetes. The aim of the present study was to investigate in non-insulin-dependent diabetic subjects the acute metabolic effects of a moderate amount of alcohol taken with a light meal, conditions chosen to mimic an everyday situation. The patients received 500 ml non-alcoholic beer with an alcohol content (ml/l) of 0 (treatment A) and 54 (treatment B) together with a light meal, implying identity of the contents of ingredients except for alcohol. We found similar serum glucose, insulin, free fatty acid and triacylglycerol responses irrespective of addition of a modern amount of alcohol. In conclusion, a moderate amount of alcohol can be taken with a meal without eliciting hypoglycaemia in non-insulin-dependent diabetic subjects.

Blood Glucose

Spectral components of short-term RR interval variability in healthy subjects and effects of risk factors.

Cardiac neural control can be estimated by frequency domain characterization of RR interval variations. This technique may become a clinical tool, as autonomic dysfunction is involved in the pathophysiology of sudden cardiac death. The study was designed to investigate 24-h cardiac autonomic control in 104 healthy subjects aged 40-77 years and to evaluate the impact of gender, age, smoking and physical training level. The sympathovagal balance was evaluated by spectral analysis of RR interval oscillations. The square-root of power of the high- (HF; 0.15-0.40) and low-frequency (LF; 0.04-0.15 Hz) bands were considered indexes of the vagal function and of the sympathovagal interaction, respectively. In addition, the precise centre frequency of the LF and HF oscillations was determined. The vagal mediated respiratory-dependent HF oscillation exhibited a clear circadian variation, and obtained the highest power values during sleep. The centre frequency was significantly lower during sleep (0.26 Hz vs 0.28 Hz), probably due to a slower respiratory frequency at night. Values for vagal tone were higher in physically trained subjects throughout the 24-h, and decreased by 13% for every 10-year increase in age; it was also reduced in smokers. The amplitude of the LF oscillation exhibited no clear diurnal variation. The mean LF/HF ratio was 3.1. LF power was much higher in males, was reduced by 15% per 10 year increase in age, and was lower in sedentary and smoking subjects, throughout the 24-h. The mean centre frequency of this component was reduced with advancing age (0.08 to 0.06 Hz from age 40 to 80 years). LF and HF power correlated positively, (r = 0.68), and 46% and 16% of the interindividual variation in LF and HF power, respectively, was explained by the four factors (gender, age, smoking, physical activity). Thus gender, age smoking and physical training level have a significant impact on the power and centre frequency of the HF and LF components. These effects must be addressed in investigations on autonomic balance.

Adult

Effects of postprandial exercise on glycemic response in IDDM subjects. Studies at constant insulinemia.

OBJECTIVE: To determine the influence of postprandial exercise on blood glucose responses in insulin-dependent diabetes mellitus (IDDM) subjects. RESEARCH DESIGN AND METHODS: Two identical test meals were served with a 7-day interval. On one occasion, a 30-min cycle exercise was performed 15 min after the meal. Patients had achieved normoglycemia by means of an artificial pancreas (Biostator) before the meals, which also ensured constant insulin infusion in the study periods. Seven IDDM subjects attending the outpatient clinic at Aarhus Kommunehospital were studied. RESULTS: The 30 min of cycling reduced postprandial blood glucose response areas by 34 +/- 12% (P < 0.01) from 638 +/- 30 to 492 +/- 61 mmol/l x 180 min (P < 0.03), whereas similar peak blood glucose values were found (13.7 +/- 0.3 vs. 12.0 +/- 1.3 mmol/l). CONCLUSIONS: Thirty minutes of moderate exercise done postprandially reduces the blood glucose response to 50 g carbohydrate by about one-third.

Adult