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Biomedical subjects

R P Michels

Publications and source records attributed to R P Michels.

At least 19 recordsLinked to original sources

Coronary heart disease after prenatal exposure to the Dutch famine, 1944-45.

OBJECTIVE: To assess the effect of prenatal exposure to maternal malnutrition on coronary heart disease in people born around the time of the Dutch famine, 1944-45. DESIGN: Historical cohort study. SETTING: Community study. PATIENTS: Singletons born alive between November 1943 and February 1947 for whom detailed birth records were available. DESIGN: The prevalence of coronary heart disease was compared between those exposed to famine in late gestation (n = 120), in mid-gestation (n = 108), or in early gestation (n = 68), and those born in the year before the famine or those conceived in the year after the famine (non-exposed subjects, n = 440). MAIN OUTCOME MEASURES: Prevalence of coronary heart disease, defined as the presence of angina pectoris according to the Rose questionnaire, Q waves on the ECG, or a history of coronary revascularisation. RESULTS: The prevalence of coronary heart disease was higher in those exposed in early gestation than in non-exposed people (8.8% v 3.2%; odds ratio adjusted for sex 3.0, 95% confidence interval (CI) 1.1 to 8.1). The prevalence was not increased in those exposed in mid gestation (0.9%) or late gestation (2.5%). People with coronary heart disease tended to have lower birth weights (3215 g v 3352 g, p = 0.13), and smaller head circumferences at birth (32.2 cm v 32.8 cm, p = 0.05), but the effect of exposure to famine in early gestation was independent of birth weight (adjusted odds ratio 3.2, 95% CI 1.2 to 8.8). CONCLUSIONS: Although the numbers are very small, this is the first evidence suggesting that maternal malnutrition during early gestation contributes to the occurrence of coronary heart disease in the offspring.

Birth Weight↗

No relationship between cerebral blood flow velocity and cerebrovascular reserve capacity and contemporaneously measured glucose and insulin concentrations in diabetes mellitus.

Blood glucose and insulin concentrations have been reported to influence cerebral hemodynamics. We studied the relationship between actual blood glucose and insulin concentrations and resting cerebral blood flow velocity in the middle cerebral artery and cerebrovascular reserve capacity after acetazolamide stimulation. Thirty-six insulin-dependent diabetic patients in a state of good glycemic control were studied. Blood samples were taken for determination of glucose and insulin concentrations. Subsequently we measured resting cerebral blood flow velocities in supine position using transcranial Doppler, administered 1 g acetazolamide intravenously, and repeated the measurements after 5, 10, 15 and 20 minutes. Cerebrovascular reserve was calculated as the maximal percent increase after acetazolamide stimulation. Multiple regression was used for statistical analysis. Blood glucose levels were not correlated with resting blood flow velocity (R = 0.21, p = 0.22) nor cerebrovascular reserve capacity (R = 0.17, p = 0.32). Similarly, no correlation was found between insulin concentrations, resting cerebral blood flow velocity (R = 0.24, p = 0.22) and cerebrovascular reserve (R = 0.26, p = 0.24). Studying patients with long-term (> 10 years) and short-term (</= 10 years) disease duration yielded the same lack of correlation. We conclude that there is no significant correlation between contemporaneously measured glucose and insulin concentrations and either cerebral blood flow velocity or cerebrovascular reserve capacity in the middle cerebral artery in type 1 diabetic patients with good control.

Acetazolamide↗

Influence of repetitive finger puncturing on skin perfusion and capillary blood analysis in patients with diabetes mellitus.

BACKGROUND: Frequent puncturing of fingers to check blood glucose in patients with type 1 diabetes might alter skin perfusion and, hence, influence the representativeness of the blood sample. We investigated the influence of repetitive puncturing on skin microcirculatory perfusion using laser Doppler fluxmetry and on the preanalytical phase of capillary blood analysis for small molecules (glucose) and large particles (cholesterol). METHODS: In 49 patients with long-standing (mean, 21 years) type 1 diabetes, with a mean puncture frequency of three times daily for a mean duration of 13 years, laser Doppler skin perfusion was measured in a finger at a frequently punctured site and compared with a similar site of another finger of the same hand, which was never punctured. In the supine position with the hand level with the heart, resting flux (RF), peak flux (PF), and the microcirculatory reserve capacity (MRC; PF - RF) were assessed. Subsequently, blood samples for capillary whole blood glucose and cholesterol analyses were taken from the same sites. RESULTS: No significant differences were found between the puncture and control sites in mean RF (2.3 vs 2.0 V; P = 0.14, paired-samples t-test), PF (3.3 vs 3.1 V; P = 0.24), MRC (1.0 vs 1.0 V; P = 0.65), glucose (10.2 vs 10.2 mmol/L; P = 0.69), or cholesterol (5.1 vs 5.2 mmol/L; P = 0.26). Power calculation for a RF of 2.0 V and the SD and n of this study indicate a power (beta) of 80% to detect a 25% change in RF at P <0.05. CONCLUSIONS: Repetitive finger puncturing in diabetics appears not to injure local skin microcirculatory perfusion nor to influence results of capillary blood analysis for glucose and cholesterol.

Adult↗

Glucose tolerance in adults after prenatal exposure to famine.

BACKGROUND: Reduced growth in utero is associated with type 2 (non-insulin-dependent) diabetes and impaired glucose tolerance in adult life. There is no direct evidence in human beings that maternal nutrition during gestation affects insulin-glucose metabolism. We investigated glucose tolerance in people born around the time of famine in the Netherlands during 1944-45. METHODS: We included 702 people born between Nov 1, 1943, and Feb 28, 1947, in Amsterdam, for whom we had detailed prenatal and birth records. We compared glucose and insulin responses to a standard oral glucose load in participants exposed to famine at any stage during gestation (exposed participants) with those who were born in the year before or conceived in the year after the famine (non-exposed participants). FINDINGS: Glucose concentrations were increased 2 h after a standard glucose load among exposed participants (p = 0.006), and were highest in men and women exposed during mid and late gestation. Mean 2 h glucose concentration among non-exposed participants was 5.8 mmol/L; concentrations were 0.5 mmol/L (95% CI 0.1-0.9) higher among participants exposed during late gestation, 0.4 mmol/L (0-0.8) higher among those exposed during mid gestation, and 0.1 mmol/L (-0.4 to 0.6) among those exposed during early gestation. Participants born as thin babies to mothers with low bodyweights had the highest concentrations and concentrations were especially high among people exposed to famine who became obese as adults. Prenatal exposure to famine was related to increased fasting proinsulin (p = 0.05) and 2 h insulin concentrations (p = 0.04), which suggests an association with insulin resistance. INTERPRETATION: Prenatal exposure to famine, especially during late gestation, is linked to decreased glucose tolerance in adults. Poor nutrition in utero may lead to permanent changes in insulin-glucose metabolism, even if the effect on fetal growth is small. This effect of famine on glucose tolerance is especially important in people who become obese.

Birth Weight↗

Impairment of cerebrovascular reactivity in long-term type 1 diabetes.

The early preclinical detection of cerebrovascular complications in individuals with diabetes is one of the goals of care described in the St. Vincent Declaration. In accordance with this goal, the aim of the present work was to investigate whether altered cerebral microvascular function in patients suffering from type 1 diabetes can be detected with a transcranial Doppler probe after the administration of acetazolamide. A total of 72 type 1 diabetic patients and 40 healthy control subjects entered the study. Patients were divided into two groups: those with long-term diabetes (disease duration of >10 years, n = 37) and those with short-term diabetes (disease duration of < or =10 years, n = 35). Mean blood-flow velocity in the middle cerebral artery (MCAV) was measured at rest and at 5, 10, 15, and 20 min after intravenous administration of 1 g acetazolamide with a transcranial Doppler probe and expressed as the percentage change from the pretest measurement. The percentage increase in MCAV (cerebrovascular reactivity) was calculated at each time point and compared between the groups. Cerebrovascular reserve capacity (CRC), expressed as the maximal percentage increase of the MCAV, was compared between the groups. Additionally, a reproducibility study of CRC was performed in 10 patients, using intraclass correlations. Cerebrovascular reactivity in the long-term diabetes group was lower (means +/- SD: 5 min, 23.4 +/- 15.4%; 10 min, 28.8 +/- 17.0%; 15 min, 30.0 +/- 15.6%; 20 min, 24.2 +/- 17.8%) than that of the control subjects (5 min, 43.5 +/- 23.9%; 10 min, 55.3 +/- 24.0%; 15 min, 56.7 +/- 23.8%; 20 min, 54.8 +/- 25.9%) and the short-term diabetic patients (5 min, 43.6 +/- 25.9%; 10 min, 52.2 +/- 27.7%; 15 min, 55.3 +/- 32.2%; 20 min, 45.8 +/- 35.8%). CRC was lower in the long-term diabetes group than in the control group or the short-term diabetes group. Impairment of cerebrovascular reactivity was associated with retino- and nephropathy and increased levels of fibrinogen. In contrast, CRC was independent from actual glucose, insulin, glycosylated hemoglobin, von Willebrand factor antigen, and alpha-2 macroglobulin levels. Transcranial Doppler measurements of the changes in MCAV after stimulation with acetazolamide can detect altered cerebral microvascular function in patients with diabetes. Cerebrovascular reactivity and reserve capacity are reduced in patients with long-term diabetes. Further prospective studies should delineate the clinical significance of our results.

Acetazolamide↗

Treatment of diabetic polyneuropathy with the neurotrophic peptide ORG 2766.

The efficacy of the neurotrophic peptide ORG 2766 in diabetic patients with polyneuropathy was evaluated in a double-blind, placebo-controlled, multicentre trial. One hundred and twenty four patients were randomised in five groups to receive 0.1, 0.4, 2 or 5 mg ORG 2766 or placebo, once daily, administered subcutaneously 52 weeks. Thermal discrimination thresholds (TDT) and vibration perception thresholds (VPT), motor and sensory nerve conduction velocity, Hoffmann reflex, heart rate variation during deep breathing and heart rate response after standing up, neurological examination score and neuropathic symptom score were determined at baseline and after 17, 34 and 52 weeks of treatment. Of the nerve function indices studied, at week 52 the TDTwarmth of the hand in the ORG 2766 0.1, 0.4 and 5 mg groups and the TDTcold of the foot in the ORG 2766 0.1 and 0.4 mg groups significantly improved compared with placebo. Further significant improvement as compared with placebo was observed in the paraesthesia score at week 34 and week 52 in the ORG 2766 2 mg group. Only at week 34 had both the heartbeat variation during deep breathing and the VPT of the foot in the ORG 2766 0.1 mg group improved significantly, compared with placebo. No further statistically significant differences were observed at time for the other measures. No adverse reactions were observed. The only recorded drug-induced side effect was pain at the injection site. Taking all measures of efficacy into account, the statistically significant results observed did not show consistency within each measure. Therefore, it is concluded that ORG 2766, in contrast to earlier reports, is not effective in treating diabetic polyneuropathy.

Adrenocorticotropic Hormone↗

Motor nerve refractory period distribution assessed by two techniques in diabetic polyneuropathy.

The techniques introduced by Kimura and Ingram et al. were applied to assess the distribution of motor refractory periods (DMRPs) in peroneal nerve fibres of 28 diabetics with symptoms indicating polyneuropathy and in 28 controls. Results were compared with conventional motor nerve conduction velocity (MNCV) and compound muscle action potential (CMAP) measurements. MRP95 and MRP90 (the 5% and 10% slowest recovering fibres) obtained with Ingram's technique were prolonged in the diabetic patients. In the 26 patients with a value of MRP95 and MNCV, a prolonged MRP95 and a decreased MNCV were found in 12 patients. Thus conventional MNCV had a sensitivity of 46% to detect neuropathy; addition of MRP95 obtained with Ingram's technique raised the sensitivity to 73%. Specificity was 100% in both cases. With Kimura's technique or with the fast recovering fibres in Ingram's technique, it was not possible to discriminate the patients from the controls. This study indicates that measurement of the DMRP with the technique introduced by Ingram et al. improves the electrophysiological diagnosis of diabetic polyneuropathy.

Action Potentials↗

No decreased erythrocyte deformability in type 1 (insulin-dependent) diabetes, either by filtration or by ektacytometry.

A lower erythrocyte deformability, which causes impairment of the microcirculation, is postulated to contribute to diabetic organ complications. Erythrocyte deformability was measured in four groups of type 1 (insulin-dependent) diabetic subjects and 30 controls by filtration and ektacytometry. Twenty-five patients without organ complications, 21 with microalbuminuria, 13 with overt nephropathy and 12 with leg ulceration were studied. No decreased erythrocyte deformability was found in any of the diabetic groups with either technique, and neither did the total group of 71 diabetic subjects have a lower erythrocyte deformability when compared with the controls. In order to imitate local conditions in the kidney, erythrocyte deformability was also measured in hyperosmolar solutions. Again no differences were found between the diabetic groups separately or as a whole and the controls. Furthermore no correlation was found between erythrocyte deformability and the plasma glucose or glycosylated haemoglobin level.

Adult↗

Blood and plasma viscosity in diabetes: possible contribution to late organ complications?

It has been postulated that an increased whole blood and plasma viscosity contribute to diabetic organ complications. Blood viscosity was measured in 30 controls and four groups of insulin-dependent diabetic patients at three shear rates: 70 sec-1, 0.5 sec-1 and 0.05 sec-1. Results were compared before and after correction for a haematocrit of 0.45. Twenty-five patients without organ complications, 21 with microalbuminuria, 13 with overt nephropathy and 12 patients with leg ulcerations were studied. Blood and plasma viscosity were normal in the patients without organ complications and with microalbuminuria. Plasma viscosity was significantly elevated in the diabetic patient with nephropathy and leg ulceration. After correction for haematocrit blood viscosity was also higher in these two groups, although this was only significant in the group with leg ulceration. In conclusion blood and plasma viscosity were only elevated in the patients with major organ complications and not in the patients without or with early complications. Therefore it is unlikely that an elevation of blood or plasma viscosity contributes early in the pathogenesis of diabetic organ damage.

Adult↗

Uveitis and diabetes mellitus.

Of 340 patients with anterior uveitis, 20 (6%) had diabetes mellitus. This is significantly higher than the prevalence of 1.4% in the normal Dutch population (P less than .001). Of 128 patients with idiopathic anterior uveitis, 16 (12.5%) had diabetes mellitus compared to only four (1.9%) of 212 patients with anterior uveitis with an established specific ocular diagnosis (P less than .001). Of the 16 diabetic patients with idiopathic anterior uveitis, ten (63%) had type I diabetes mellitus and 12 (75%) suffered from severe diabetic complications as angiopathy, nephropathy, and neuropathy. The onset of diabetes mellitus preceded the onset of anterior uveitis in all cases. Whether or not uveitis in diabetic patients is a true inflammation rather than an ischemic phenomenon is still unknown.

Diabetes Complications↗

Relationship between turnover rate and oxidation rate of alanine in the post-absorptive state and during parenteral nutrition before and after surgery.

The influence of total parenteral nutrition and stomach resection on alanine turnover rate and alanine oxidation rate was measured in ten patients after single injection of U-14 C-alanine. Sequential studies were done in three patients. During parenteral nutrition alanine turnover was significantly higher than in the post-abortive state (14.75 +/- 2.56 mumol kg-1 min-1 and 8.48 +/- 1.88 mumol kg-1 min-1, respectively; P less than 0.01, mean +/- s.d.). Surgery had no additional significant influence on alanine turnover. In the post-absorptive state 4.71 +/- 0.71 mumol kg-1 min-1 was oxidized, during parenteral feeding before surgery 7.93 +/- 1.93 mumol kg-1 min-1 (P less than 0.01 v. post-absorptive state), and during parenteral feeding after surgery 7.67 +/- 1.67 mumol kg-1 min-1. The percentages of alanine turnover used for oxidation in the post-absorptive state and during parenteral feeding before and after surgery were 57 +/- 11%, 54 +/- 7% and 45 +/- 11%, respectively (no significant differences). It is concluded that the degree of alanine oxidation seems to be directed by the degree of alanine turnover. A discussion about differences in alanine oxidation under different circumstances must therefore include a discussion about changes in alanine turnover.

Absorption↗

The relationship between gluconeogenesis from alanine and insulin, glucagon, cortisol and catecholamines after stomach resection.

A hormonal influence on gluconeogenesis after stomach resection was sought by correlating the degree of carbon flux from alanine to glucose with the plasma levels of insulin, glucagon, adrenaline, noradrenaline and cortisol and with the urinary excretion of catecholamines, (nor)metanephrines and cortisol. No correlation was found, suggesting that none of these hormones has a dominant influence on gluconeogenesis after stomach resection.

Journal Article↗

Endogenous glucose production after stomach resection.

Endogenous glucose production was measured in eight patients after stomach resection to determine glucose requirement after elective surgery in five patients during infusion of 2.1 - 2.9 g glucose.kg/day (low glucose) and in three patients during infusion of 6.2 - 6.9 g glucose.kg/day (high glucose). Endogenous glucose production was defined as the difference between total glucose turnover measured by 2-3H-glucose and the glucose infusion rate. Endogenous glucose production was the same in both groups, respectively 0.010 +/- 0.002 and 0.009 +/- 0.002 mmol kg/min. It was concluded that a daily quantity of glucose equal to the endogenous production of 180 g. 70 kg/day should be the minimum given after stomach resection.

Journal Article↗

Alanine turnover in the postabsorptive state and during parenteral hyperalimentation before and after surgery.

Influence of total parenteral nutrition and operation on alanine turnover and venous alanine concentration was determined in 5 patients with stomach carcinoma using single technique of U-14C alanine. Every patient served at his own control. In the postabsorptive state alanine turnover was 1.63 +/- 0.31 mgatC . min-1, not different from a control group (1.84 +/- 0.60 mgatC . min-1); during total parenteral nutrition alanine turnover increased to 3.21 +/- 0.5g mgatC . min-1 with a rise in alanine concentration from 0.96 +/- 0.17 mgatC . L-1 + 0.69 +/- 0.22 mgatC . L-1. After surgery during the same total parenteral nutrition alanine turnover increased further to 3.78 +/- 0.17 mgatC . min-1 with a lowering of alanine concentration to 1.44 +/- 0.22 mgatC . L-1. The present results show the distinct influence of TPH on alanine kinetics. The present data indicate that alanine turnover cannot be deduced from blood alanine concentration.

Absorption↗