Effects of diet fat P/S ratio on serum lipoprotein concentrations.
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The effects of moderate addition of leguminous seeds to a mixed diabetic diet were evaluated in 15 inadequately controlled patients with non-insulin-dependent diabetes mellitus. A control diet and a diet with an increased content of peas and beans (leguminous diet) were given consecutively for a 3-week period each on a metabolic ward. Seven of the patients started with the control diet and 8 with the leguminous diet. On an energy basis the diets comprised 20% protein and 33-34% fat, the ratio between polyunsaturated and saturated fatty acids was 1.4. The analysed dietary fibre contents of the control and leguminous diets were 24 and 37 g/day per 6.7 MJ (1,600 kcal) respectively. The content of digestible carbohydrates was similar in the 2 diets. The mean body weight did not differ after the 2 dietary treatment periods. All patients showed improved glucose control during treatment irrespective of the type of diet given. The fasting blood glucose concentration on admission was 14.3 +/- 0.9 mmol/l (mean +/- SEM). This value had decreased to 9.9 +/- 0.8 during the last week of the control period and to 9.7 +/- 0.6 during the last week of the leguminous diet period. The mean postprandial glucose concentration at 3 pm was significantly lower during the leguminous diet period. The mean urine glucose excretion was significantly lower during the leguminous diet period. The fasting serum lipid concentrations decreased during treatment with each diet, but there were no significant differences between these values at the end of the 2 diet treatment periods.(ABSTRACT TRUNCATED AT 250 WORDS)
Microelectrode recordings of skin nerve sympathetic activity, consisting of sudomotor and vasoconstrictor signals, were performed in the peroneal nerve in seven healthy subjects during insulin-induced hypoglycaemia. The nerve activity was recorded at rest and for 90 min after intravenous injection of 0.15 IU insulin/kg body weight. The net outflow of skin nerve sympathetic activity was increased during hypoglycaemia, with the exception of one subject who exhibited a high initial level of activity. In all subjects a change of the temporal pattern of the outflow was found, suggesting a shift from mixed (sudomotor and vasoconstrictor) to pure sudomotor activity. This change coincided with a sensation of warmth, sweating and varying degrees of cutaneous vasodilatation, and was followed by a fall in body temperature. It is concluded that hypoglycaemia has a differential effect on sympathetic activity in skin nerves, with a strong increase of sudomotor impulses and simultaneous inhibition of vasoconstrictor signals. Thus, neurally mediated thermoregulatory adjustment contributes to heat loss during hypoglycaemia.
The increased incidence of the idiopathic respiratory distress syndrome (IRDS) in infants of diabetic mothers may be explained by preterm delivery and asphyxia but the metabolic derangement per se may also be responsible for the inadequate production of surfactant. Experimental studies of the underlying mechanisms in the lungs of fetuses of pregnant diabetic rats have shown a decreased formation of the two major surfactant phospholipids disaturated phosphatidyl choline and phosphatidyl glycerol. In addition, the activities of key enzymes responsible for the production of these phospholipids are decreased in the fetal lung tissue. Inadequate utilization of pulmonary glycogen for surfactant biosynthesis has also been observed. Furthermore, experimental studies support that other changes than fetal hyperinsulinaemia are needed to produce a state of disturbed surfactant production. In human diabetic pregnancy strict metabolic control allows the fetal lungs to mature in a near-normal fashion. The presence of phosphatidyl glycerol in the amniotic fluid seems to be the best available predictor of lung maturity in diabetic pregnancy, in which both the lecithin/sphingomyelin ratio and amniotic fluid cytology may result in false-positive and false-negative values. The trend towards extension of delivery to term will undoubtedly diminish the need for estimation of fetal lung maturity by amniocentesis. Avoiding preterm delivery and adhering to strict metabolic control of the maternal diabetes would be expected to decrease the neonatal respiratory problems in diabetic pregnancy.
The normal response to insulin-induced hypoglycemia bears many characteristics of activation of the sympathetic nervous system. In this study, the impulse pattern of muscle nerve sympathetic activity (MSA) involved in cardiovascular homeostasis was identified by microneurography in the peroneal nerve of seven healthy and two adrenalectomized subjects. After recordings at rest and an intravenous injection of 0.15 IU insulin/kg body wt (0.10 IU insulin/kg body wt in adrenalectomized subjects), MSA was followed for 90 min. Nadir of hypoglycemia (2.0 +/- 0.1 mM) was reached at 30 min. All subjects, including the two adrenalectomized subjects, exhibited an increase of MSA, which peaked at the glucose nadir. The time course of MSA increase was a mirror image of the blood glucose curve. This directly measured increase of MSA may be part of the hemodynamic adjustment to the fall in plasma volume known to occur in hypoglycemia. Another possible cause is direct stimulation of central sympathetic motoneurons.
The frequency of anorectic/bulimic disturbances in a sample of male and female subjects with insulin-dependent diabetes mellitus was compared to that of male and female normal controls. The results suggest an overrepresentation of anorexia/bulimia in the female diabetics. Prevalence of eating disorders was determined from the scores on the Eating Attitudes Test. As a group, the female diabetics had significantly (p less than .05) higher scores on the test, suggesting a greater "awareness" of topics related to food and eating. The results are discussed within a risk-factor model, in which insulin-dependent diabetes mellitus may be viewed as one factor in the development of eating disorders.
The effects of the aldose reductase inhibitor, sorbinil, on symptomatic symmetrical diabetic polyneuropathy were studied during a 6-month period in a double-blind parallel group placebo-controlled trial. Twenty-seven patients received sorbinil and 28 placebo. The patients were assessed by clinical examination, neurophysiological measurements, sensory threshold determinations and tests of autonomic nerve function. No major clinical benefit was seen in the sorbinil-treated patients and no differences in sensory thresholds were observed. In three out of nine neurophysiological tests (motor nerve conduction velocity of the posterior tibial nerve, F-wave latency and sensory distal latency of the ulnar nerve) and one out of five tests of autonomic nerve function (heart rate variation during deep breathing) significant differences between the patient groups evolved in favour of sorbinil treatment. An overall evaluation of the temporal development of these and remaining neurophysiological and autonomic variables suggested a small but significant benefit from sorbinil treatment. There was no evidence of continuing improvement throughout the treatment period and beneficial effects observed were no greater than those seen in previous trials of considerably shorter treatment periods. It is concluded that sorbinil treatment results in some improvement in peripheral nerve function in symptomatic diabetic polyneuropathy, but that the long-term effect may be of limited value.
Poorly controlled type 2 diabetes represents a major therapeutic problem. A classification of the disease, based on body weight and presence or absence of adequate insulin-secretion capacity, may be helpful in the choice of correct treatment. Calorie reduction is the most important therapeutic intervention in overweight patients. In the diabetic diet digestible carbohydrates should comprise at least 50 energy%, while the fat content should be reduced below 30 energy%. Controlled clinical studies show that the blood glucose control can be improved and the urinary glucose excretion be diminished by addition of dietary fibre. In obese type 2 diabetics supplemented fasting may be useful to achieve a rapid weight loss and an improved metabolic control. Although our knowledge with regard to the patho-physiology of type 2 diabetes and the effects of dietary treatment has increased during recent years, several important questions remain unanswered. Also there is a great need for education and training programmes to achieve improved compliance to the dietary advice given.
Between 1975-1984, 119 women with gestational diabetes (GDM) were treated with insulin in Uppsala, representing a mean yearly incidence of 4.5/1,000 pregnancies. Women with GDM were older and more obese than the general pregnant population. Insulin treatment was instituted during a 5-7 day stay in hospital. The mean total daily dose of insulin prepartum, when fasting blood glucose had been normalized, was 53 (SD +/- 25) units (34 +/- 15 units of rapid-acting and 20 +/- 11 units of medium-acting insulin), divided into two doses daily. Mean duration of treatment was 6.4 weeks. The perinatal mortality was 0.8%, compared with 7.4% in previous pregnancies in the same women. The perinatal morbidity was generally mild and included hypoglycaemia (10.9%), hyperbilirubinaemia requiring treatment (2.5%), shoulder dystocia (2.5%) and one case of mild respiratory distress syndrome. The rate of macrosomia was reduced in the present pregnancies compared with previous ones in the women with GDM, but not abolished completely, probably because of too short a duration of improved metabolic control. Spontaneous delivery was favoured and the rate of Caesarean section was 13.5%. Thus, treatment with high doses of insulin in an unselected group of women with GDM is feasible. Normal perinatal mortality, reduced macrosomia, and no gross perinatal morbidity was found in the infants. Though the extent to which insulin treatment per se contributed to the favourable outcome is difficult to assess, it is suggested that the case for a high level of ambition for metabolic normalization in GDM should be a subject of further study.
In diabetic pregnancy near-normalization of maternal blood glucose levels improves the perinatal outcome. Strict metabolic control can be achieved by self-monitoring of blood glucose in ambulant praxis. The obstetric supervision may now therefore be organized on an out-patient basis aiming at early recognition of pregnancy complications such as preeclampsia and deviation in fetal growth. For uncomplicated and well-controlled diabetes without vascular complications the obstetric care should be individualized and routine programmes for obstetric surveillance, such as fetal heart rate monitoring and determination of fetal maturity, are usually not necessary. Special attention should, however, be paid to patients with poor metabolic control or vascular complications, particularly in the presence of disturbances of intra-uterine growth.
Since continuous ambulatory peritoneal dialysis (CAPD) causes losses of certain plasma proteins and their ligands, we examined the serum concentrations of vitamin A and retinol-binding protein (RBP), as well as the concentrations of vitamin A in the skin and dialysis fluid from 32 patients on CAPD over a period of 1-30 months (mean 7.5). The mean values of vitamin A and RBP in serum were 2-4 times higher than those in the healthy controls; a consistent finding in patients with chronic renal failure. Similarly, the vitamin A concentrations in skin were elevated in the CAPD patients (p less than 0.01). The vitamin A content of the dialysate (mean 1.4 mumol/24 h), which correlated significantly with the serum vitamin A concentration (r = 0.67), was constant during CAPD treatment. RBP was present in the dialysate and its concentration closely correlated with that of vitamin A (r = 0.95), indicating that the transperitoneal diffusion involved retinol-RBP. This conclusion was supported by calculations of clearance rates. Despite the considerable losses of vitamin A in CAPD fluid, the patients' vitamin A concentrations in serum and skin remained elevated. Whether extended CAPD treatment (greater than 30 months) may eventually affect the vitamin A situation in chronic renal failure warrants further observations.
We have previously demonstrated that gestational age can be estimated from a diagram in which the percentage of lipid-carrying cells (amniotic fluid cytology) and the creatinine concentration in the amniotic fluid are plotted. Using this diagram for the purpose of dating, a comparison was made with prediction of gestational age by early ultrasound (biparietal diameter, BPD). Dating by the two methods showed a high correlation (r = 0.72) in 53 samples from 48 pregnancies and the two methods were in agreement within 2 weeks in 94%. In one third of infants with a low birth weight for age, however, amniotic fluid tests overestimated gestational age in comparison with early BPD. It is suggested that this disparity may be due to a combination of influence of early growth retardation on the BPD and accelerated maturation accompanying intrauterine growth retardation. Prior to elective delivery in pregnancies with uncertain dates and when an early ultrasonic examination has not been performed dating by amniotic fluid tests is reliable and is particularly useful.
The cytosolic Ca2+ activity was measured with the fluorescent indicator quin-2 in pancreatic beta-cells obtained from obese-hyperglycemic mice. When present at a concentration of 20 mmol/l in a medium physiologically balanced in cations, glucose induced a rise of cytosolic Ca2+ after a delay of 1--3 min. At lower concentrations of extracellular Ca2+ this effect was not only prevented but the sugar promptly reduced the cytosolic Ca2+ activity. The dual effect of glucose on cytosolic Ca2+ had its counterpart in the release of insulin. Whereas 20 mmol/l of glucose stimulated the release of insulin from mouse islets previously stored in a Ca2+-deficient medium, the sugar was clearly inhibitory when present at a concentration of 6 mmol/l. Intravenous glucose tolerance tests revealed a temporary glucose depression of the serum concentrations of insulin and C-peptide in several patients with diabetes. In a mentally retarded girl with hyperinsulinemia associated with acanthosis nigricans the glucose suppression of circulating insulin was prolonged and sufficiently pronounced to suggest an almost complete inhibition of the secretory activity of the pancreatic B-cells.
The metabolic effects of the alpha 1-adrenoceptor blocking drug prazosin was evaluated in 8 premenopausal women undergoing treatment for essential hypertension. Intravenous glucose tolerance (IVGTT) and the early insulin response was studied before treatment, after 1 and 12 months and 3 weeks after cessation of drug treatment. The k-value for the glucose disappearance decreased from 2.9 to 2.0 after 1 month. No further change occurred after 12 months. After cessation of the drug the k-value returned to the pre-treatment level. The decreased glucose tolerance was accompanied by a decrease in the early insulin response. It is suggested that the reversible decrease in glucose tolerance is due to an inhibition of the early insulin response, mediated by the increase in circulating catecholamines reported during prazosin treatment.
Pancreatic islets accumulate the amphiphilic drug, chloroquine, which leads to a marked impairment of the insulin production of the B-cells in vitro. In this study the effects of the drug on islet lipid metabolism in vitro were investigated. It was found that exposure of islets to chloroquine (10(-5) M) for one week induced an increase of D-[U-14C]glucose incorporation into phospholipids and triacylglycerols of about two-fold and into diacylglycerols of about six-fold. Furthermore, two-dimensional thin-layer chromatography showed an increased rate of D-[U-14C]glucose incorporation into all major phospholipid classes. A 17% increase of the total islet phospholipid content indicated that an accumulation of islet cell phospholipids occurred. Pulse-chase experiments with D-[U-14C]glucose showed that the rate of degradation of islet phospholipids was decreased after prolonged exposure to chloroquine. No short-term effects of chloroquine upon either the de novo biosynthesis of islet lipids or upon phospholipid degradation could be demonstrated. The present data therefore suggest that chloroquine impairs the rate of islet lipid degradation in long-term experiments, which may be a primary lesion in the sequence of events leading to functional impairment of the B-cell.
The effect of phototherapy on uraemic pruritus and vitamin A content in serum and epidermis was investigated in ten patients with chronic renal failure. The patients and five healthy controls were given repeated whole-body irradiation of UV-A + UV-B (total dose 7.9 + 1.3 J cm-2). Serum and skin samples were obtained before and after the treatment. Serum samples were analysed for retinol, retinol-binding protein and carotene and epidermis samples for retinol, 3-dehydroretinol and carotene. Before treatment, the retinol concentrations in serum and epidermis were higher in patients than in controls. The treatment, which relieved seven patients of pruritus, reduced the epidermal retinol from 11.6 +/- 4.5 to 7.0 +/- 3.8 nmol g-1 protein (P less than 0.02). A similar reduction occurred in the controls (4.5 +/- 1.0 v. 1.7 +/- 1.0, P less than 0.01). No changes of epidermal 3-dehydroretinol, carotene or the serum parameters occurred in either patients or controls. The putative relationship between uraemic pruritus and hypervitaminosis A and the response of this condition to UV therapy is discussed.
The concentrations of C-peptide and phosphatidylglycerol in the amniotic fluid were determined in 36 pregnant diabetic women. Twenty-one patients who were being treated with insulin for gestational diabetes as well as 15 patients who were insulin dependent were studied. All patients were subjected to a program of strict metabolic control, and amniocentesis was performed at gestational week 36-37. Phosphatidyl glycerol was present in the amniotic fluid in 15 cases and absent in 21. The mean concentration of C-peptide did not differ whether phosphatidyl glycerol was present or absent. (C-peptide: 0.56 +/- 0.06 and 0.43 +/- 0.05 nmol/l respectively). Although the mean value for amniotic fluid C-peptide in both groups was close to that in diabetic pregnancies with an uneventful neonatal outcome, it was significantly higher than that in non-diabetic pregnancies, indicating minor fetal hyperinsulinemia. The level of C-peptide in the amniotic fluid showed a correlation to the subsequent birthweight of the infant (r = 0.50; p less than 0.01). It is concluded that with rigorous metabolic control of the pregnant diabetic patient, the presence or absence of phosphatidyl glycerol, as an index of fetal lung maturity, is apparently not related to the level of C-peptide in the amniotic fluid.
In 56 strictly controlled diabetic pregnancies, altogether 60 amniotic fluid samples were analysed for their content of lipid-carrying cells and the presence of phosphatidylglycerol. The outcome of the amniotic fluid tests was examined for its association to macrosomia and to minor neonatal complications such as hypoglycaemia, hypocalcaemia, respiratory disturbances and hyperbilirubinaemia. The predictive value of these tests was nil, since all cases of neonatal complications occurred in the group showing maturity in tests at week 37. At term, phosphatidylglycerol was detected in 80% of the pregnancies, a finding corresponding to our observations in non-diabetic pregnancies. Lipid-carrying cells were present in quantities indicating maturity (greater than or equal to 10%) in 65% of the pregnancies at term, compared with 87% in non-diabetic pregnancies, suggesting a somewhat disturbed skin maturation secondary to the maternal diabetic state. The failure of these tests to predict neonatal complications indicates that other factors may be of more importance for the occurrence of these disorders than those aspects of final functional maturation of the fetus that are reflected in these two particular maturity tests.