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Biomedical subjects

O Faber

Publications and source records attributed to O Faber.

At least 19 recordsLinked to original sources
PubMed1990

[Non-insulin-dependent diabetes mellitus. Diagnosis and treatment. An interpretation].

There are approximately 100,000 non-insulin-dependent diabetics in the Danish population and the incidence appears to be increasing. As the disease is complicated by a series of arteriosclerotic manifestations together with hypertension and eye changes, it presents great problems in the primary and also in the secondary sector. The Danish Association for Internal Medicine has, on this basis, prepared an explanatory report with the main object of establishing guidelines for treatment of the disease both medically and by organisation. The report contains a review of the patho-physiological conditions with emphasis on resistance to insulin and the basic cellular defect. The connections with arteriosclerosis and hypertension are also emphasized. The significance of the diet in the treatment of the condition is also emphasized as approximately 80% of the patients are overweight. Guidelines for treatment with sulphonurea, biguanides and insulin are presented. In order to provide optimal treatment and control of non-insulin-dependent diabetics and to provide them a better quality of life closer cooperation between general practitioners and diabetic clinics is recommended. In particular, it appears to be desirable to involve diabetic clinics at the commencement of the disease when the need for training is great.

Adult↗
PubMed1989

Sulphonylurea antidiabetic drugs. An update of their clinical pharmacology and rational therapeutic use.

Apart from the amelioration of symptoms, a major aim of the treatment of non-insulin-dependent diabetes mellitus (NIDDM, type 2 diabetes) should be the prevention of cardiovascular complications. These are associated with the chronic hyperglycaemia that is characteristic of NIDDM, and the risk of complications is already increased in subjects with impaired glucose tolerance (IGT). For these reasons, and because hyperglycaemia appears to be a self-perpetuating condition, treatment should be introduced as early as possible and should be aimed at normalisation of blood glucose. To enable early detection and intervention, screening is necessary. As diet regulation alone rarely suffices to normalise blood glucose, addition of sulphonylurea drugs is indicated in many cases. If introduced in the IGT phase, sulphonylureas drugs combined with diet regulation may postpone the development of IGT to manifest NIDDM, and may reduce the increased risk of cardiovascular morbidity and mortality. Sulphonylureas stimulate insulin release, possibly via interaction with receptors in the pancreatic B cells. In addition, such treatment enhances the reduced insulin action. This might be a primary effect but is also a consequence of the increased access to insulin and the subsequent reduction of hyperglycaemia. Sulphonylureas may enhance insulin availability by reducing insulin clearance. Effects on blood lipids are probably secondary phenomena. Fast and short acting sulphonylureas may improve the impaired meal-induced acute insulin release. If combined with weight-reducing diet regulation and introduced early, such treatment can maintain (near) normal blood glucose levels and an improved insulin action for several years without increasing basal insulin secretion, without chronic hyperinsulinaemia, and without weight increase. If not combined with diet regulation, sulphonylurea therapy is likely to fail. If introduced when NIDDM is advanced, the efficacy of these drugs is limited, with secondary failures developing at a rate of 5 to 10% per year. Continuous (24-hour-a-day) exposure to drug treatment could possibly desensitise the B cell to sulphonylurea stimulation. 'Second-generation' sulphonylurea drugs have a higher potency than 'first-generation' drugs, but this need not signify a greater clinical efficacy. The effect of several of these drugs may be increased if they are ingested half an hour before meal(s). Short acting sulphonylureas may be safer than long acting ones, which seem more likely to cause long lasting and fatal hypoglycaemia, at least in elderly patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes Mellitus, Type 2↗
PubMed1988

Insulin action and insulin secretion in identical twins with MODY. Evidence for defects in both insulin action and secretion.

To evaluate the pathogenetic mechanisms responsible for development of diabetes in the genetically inherited disease maturity-onset diabetes of the young (MODY), we have investigated a pair of identical twins (19 yr old) from a MODY family. One twin had nondiabetic fasting plasma glucose values but impaired glucose tolerance (IGT), whereas the other suffered from frank diabetes (fasting plasma glucose 12.5 mM). Differences in insulin secretion pattern and/or insulin action between the twins is supposed to be responsible for development of hyperglycemia in MODY. On the other hand, identical defects in insulin secretion and action in the twins may point to the primary genetic defect in MODY. Therefore, our aim was to investigate insulin secretion and insulin action in the twins to find these differences and similarities. We found that fasting plasma insulin and C-peptide values were slightly increased in the twins, whereas the responses of insulin and C-peptide to oral glucose tolerance tests (OGTT) and meals were similar in the twins and within normal range. The insulin responses to OGTT were, however, lower than expected from the glucose values, indicating a beta-cell defect. Despite elevated plasma insulin levels, basal hepatic glucose output (HGO) was normal in the IGT twin but increased by 75% in the diabetic twin. The maximally inhibitory effect of insulin on HGO, when estimated at euglycemia, was normal in the IGT twin but reduced by 60% in the diabetic twin. Furthermore, the maximal insulin-mediated glucose uptake in peripheral tissues was reduced by 40% in the diabetic twin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1984

Splanchnic extraction of 3,3'-diiodothyronine and 3',5'-diiodothyronine in hyperthyroidism.

The splanchnic extraction of 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) was studied in 7 hyperthyroid patients and 20 normal subjects employing the hepatic venous catheterization technique. A significant net uptake by splanchnic tissues was found for both diiodothyronines . The fractional splanchnic extraction calculated as the arterio-hepatic venous plasma concentration difference divided by the arterial concentration was unaffected by hyperthyroidism as compared to normal values. There was a close positive correlation between the arterio-hepatic venous concentration difference and arterial concentration, 3,3'-T2: r = 0.988, and 3',5'-T2: r = 0.932 (P less than 0.001). The splanchnic extraction was nonsaturable at endogenous plasma concentrations of 3,3'-T2 up to at least 17.0 ng/dl and of 3',5'-T2 up to at least 15.2 ng/dl. The data suggest that the splanchnic extraction of 3,3'-T2 and 3',5'-T2 obeys first order kinetics, the fractional extraction being unaffected by hyperthyroidism. Furthermore, changes in the net splanchnic extraction of 3,3'-T2 and 3',5'-T2 do not seem to contribute to changes in circulating levels of these iodothyronines. It is suggested that tissues other than the liver contribute significantly to the deiodination process both in normal and in hyperthyroid man.

Adolescent↗
PubMed1982

Effect of bicycle exercise on insulin absorption and subcutaneous blood flow in the normal subject.

Elimination of 8 units 125I-insulin and 99mTc-pertechnetate from a subcutaneous depot on the thigh or the abdomen was studied at rest and during intense bicycle exercise in healthy postabsorptive volunteers. Disappearance rates of the tracers as well as plasma insulin and glucose concentrations were determined before, during and after the 20 min exercise period, and compared to corresponding values obtained during a non-exercise, control study on another day. Leg exercise caused a two-fold increase in the rate of 125I-insulin disappearance from a leg depot (first-order rate constants rose from 0.68 +/- 0.15 to 1.12 +/- 0.12% . min-1, P less than 0.05), but had no significant effect on the rate of disappearance from an abdominal depot (rate constants were 0.75 +/- 0.17 and 0.87 +/- 0.18% . min-1 at rest and during exercise, respectively). 99mTC-pertechnetate clearance from leg or abdomen showed no significant change during exercise, indicating that subcutaneous blood flow was unaltered. Leg, but not abdominal, injection of insulin was associated with a greater rise in plasma insulin during exercise than at rest. The average difference between exercise and control insulin area-under-curve in the leg group (1426 +/- 594% . min) was significantly greater (P less than 0.05) than that from the abdominal group (298 +/- 251% . min). When the data from the two study groups were pooled, a direct relationship was found to exist between the change in 125I-insulin disappearance rate and the change in plasma insulin concentration (r = 0.61, P less than 0.02). Plasma glucose levels fell throughout the observation period both during the exercise and the control study, following leg as well as abdominal injection. The glucose decremental area was greater during exercise than at rest both following leg (P less than 0.05) and abdominal injection (P less than 0.01). The exercise-induced mean reduction in plasma glucose was 60% lower following abdominal injection, but this difference was not significant. In conclusion, the present results demonstrate that, in healthy subjects in the postabsorptive state (a) intense physical exercise of short duration can accelerate the absorption of subcutaneously injected insulin; (b) the effect is more pronounced at injection sites near the exercising parts; (c) an increase in subcutaneous blood flow is not the main reason for this effect.

Adult↗
PubMed1982

Therapeutic effect of tolbutamide in non-insulin dependent diabetes mellitus (NIDDM). Relation to beta-cell function.

The therapeutic effect of tolbutamide (1.5 g daily) in a random sample of patients with non-insulin dependent diabetes mellitus (NIDDM), was studied in a controlled, double-blind cross-over trial of 13 women and 6 men, aged 40-65 years and of 85-155% ideal body weight. The trial comprised C-peptide determinations during a standard carbohydrate rich meal followed by four periods of 3 months in which alternating tolbutamide and placebo were given. From the beginning to the end of the treatment periods fasting blood glucose was reduced from 11.9 +/- 1.1 (mean +/- SEM) to 10.0 +/- 0.8 mmol/l (P less than 0.025), glycohaemoglobin from 12.8% +/- 0.7 to 11.3% +/- 0.5 (P less than 0.02) with a close correlation between fasting blood glucose and glycohaemoglobin (r = 0.87, P less than 0.001). The observations during the first 3 months of study was not included in the calculations. Fasting C-peptide and fasting insulin concentrations were not significantly altered by tolbutamide treatment. The effect of tolbutamide was inversely correlated to the C-peptide response to the standard test meal at the start of the trial (r = 0.76, P less than 0.01), so that patients with the most pronounced beta-cell failure had the greatest therapeutical effect. The beta-cell response to the test meal could not identify patients, whose fasting blood glucose would be normalized by tolbutamide treatment.

Adult↗
PubMed1981

No effect of bromocriptine in acromegaly: a controlled trial.

Although bromocriptine, a dopamine receptor agonist, is now widely used in the treatment of acromegaly, there have been no controlled trials of its biochemical or clinical effects on this disorder. We assessed its effects in a double-blind, crossover study. Eighteen patients with acromegaly were given bromocriptine and placebo alternately for three months per medication. Their responses to oral glucose-tolerance tests during the two regimens did not differ significantly. The number of patients noting amelioration of clinical symptoms during treatment with bromocriptine was almost identical to the number with clinical improvement during placebo. We conclude that it remains doubtful whether bromocriptine has a beneficial effect in acromegaly.

Acromegaly↗
PubMed1978

Persistent insulin secretion, assessed by plasma C-peptide estimation in long-term juvenile diabetics with a low insulin requirement.

In order to investigate whether patients with long-standing juvenile diabetes mellitus (onset of diabetes before the age of 30) and a low daily insulin requirement (less than 0.50 units/kg body weight) still have functioning B-cells, plasma C-peptide was determined after stimulation (OGTT and glucagon/tolbutamide) in 64 patients with diabetes of more than 18 years' duration (mean 31 years). Measurable endogenous insulin production was found in 24% of the patients. The prevalence of severe retinopathy was lower in the secretors than in the non-secretor group. There was no difference in insulin antibody concentration between the two groups. Furthermore, the insulin requirement in the secretor group was relatively constant during the course of diabetes. Metabolic control was similar in both groups. It is concluded that a persisting but low activity of endogenous insulin production can be found in many long-term juvenile diabetics with a low insulin requirement, while others without any residual beta-cell function develop a low insulin requirement for unknown reasons.

Adult↗
PubMed1978

Hypomagnesemia, a risk factor in diabetic retinopathy.

The serum magnesium concentration was measured in 71 insulin-treated diabetic outpatients who had had the disease for 10 to 20 years. The patients were divided into two subgroups according to the severity of their retinopathy. As a whole the patients exhibited a definite hypomagnesemia (P less than 0.001) that was most pronounced in the subgroup having the severest degree of retinopathy (P less than 0.01). The subgroups were comparable regarding known risk factors implicated in diabetic retinopathy. Thus, hypomagnesemia appears to be an additional risk factor in the development and progress of this complication.

Adolescent↗
PubMed1977

C-peptide and insulin during blockade of the hyperglycaemic response to surgery by epidural analgesia.

UNLABELLED: Insulin secretion, as expressed by peripheral plasma insulin and C-peptide levels, was studied during and after abdominal hysterectomy in six patients having general anaesthesia and in six patients having epidural analgesia. The hyperglycaemic response to surgery was abolished during epidural analgesia. Insulin as well as C-peptide levels in plasma were low and unchanged during general anaesthesia and low and slightly decreasing during epidural analgesia. CONCLUSIONS: (1) Insulin secretion to the hyperglycaemic stimulus is blocked during surgery: (2) abolition of the hyperglycaemic response to surgery by epidural analegesia is not caused by an increased insulin secretion.

Adult↗
PubMed1976

The metabolism of cyclophosphamide. Dose dependency and the effect of long-term treatment with cyclophosphamide.

Studies on the metabolism of cyclophosphamide-14C were performed in 10 subjects at different single dose levels within the range of 0.02-10 mg/kg body-weight and in five subjects before and following an average 22 days treatment with cyclophosphamide in daily doses of 2 mg/kg. The parameters of cyclophosphamide metabolism--serum half-life of unchanged cyclophosphamide, serum concentration of metabolites, and rates of excretion of cyclophosphamide and metabolites in the urine--were all independent of dose. No change of the metabolism was demonstrated after treatment with cyclophosphamide for 22 days.

Cyclophosphamide↗