Hyperinsulinaemia accompanies the development of pre-elcampsia - abstract

Hyperinsulinaemia with insulin resistance has been observed in pre-eclampsia. In this longitudinal study, we examined whether this state of insulin resistance preceded the development of eclampsia. At 12, 24 and 36 weeks of gestation and at 12 weeks post-partum in twenty-five primigravidae, insulin and glucose were measured in the fasting state and in samples collected during intravenous glucose tolerance tests (IVGTT). Five women were diagnosed as pre-eclamptic (PE) at 34 - 39 weeks' gestation. In these PE, there was hyperinsulinaemia in the fasting state at 24 weeks compared to the normal pregnant (NP) women, 20.07 ñ 8.31 mU/ml vs. 13.74 ñ 5.64 mU/ml, (p<0.05). The degree of hyperinsulinaemia increased and, at 36 weeks' gestation it was 26.4 ñ 7.7 mU/l in the PE compared to 13.1 ñ 6.1 mU/l in the NP, (p<0.0001). The sensitivity of this measure for predicting pre-eclampsia at mid-pregnancy (24 weeks) was 80 per cent which increased to 100 per cent in late pregnancy (36 weeks). The specificity of this measure went from 57 per cent in mid-pregnancy to 43 per cent in late pregnancy. The glucose levels in the fasting state were not different at any time in the study. In the IVGTT, the area under the insulin curve was significantly larger in the PE as a group compared to the NP, (p<0.05). The area under the glucose curve was not different between the two groups at any time. The rate of disappearance of glucose Kg was significantly larger in the PE as a group compared to the NP, (p<0.05). Hyperinsulinaemia in the fasting state precedes the development of pre-eclampsia. It has a high sensitivity but low specificity for predicting the development of pre-eclampsia. Hyperinsulinaemia in the fasting state may have some value in screening those primigravidae at risk for developing pre-eclampsia (AU)

Zinc intake and plasma insulin-like growth factor-I (IGF-I) in Jamaican malnourished children - abstract

The effect of zinc intake on plasma immunoreactive insulin-like growth factor-I (IR-IGF-1) was studied in 24 children (aged 3 to 24 mos) recovering from severe malnutrition. The children were randomly assigned to two groups for zinc supplementation. Twelve (Zn+) were given (2mg/kg/d) added to the recovery of diet, and 12 (ZN-) were not. There was no group difference in age, sex, anthropometric measurements or plasma IR-IGF-1 at baseline. Plasma IR-IGF-1 was significantly higher in the zinc supplemented children during recovery (p = 0.031). These results suggest that zinc intake stimulates IR-IGF-1 production. (AU)

The effect of malnutrition on insulin binding to rat erythrocytes

Insulin binding to erythrocyte receptors was compared in malnourished and control rats. Percentage specific insulin binding to malnourished rat erythrocytes was significantly lower than to control erythrocytes (P<0.001). The low insulin binding in the malnourished rat erythrocytes was accompanied by low insulin receptor affinity (P=0.035).(AU)

Fasting plasma insulin and C-peptide levels in pre-eclampsia - abstract

In this study, plasma insulin, C-peptide and glucose measurements were done on the fasting blood samples obtained from primigravid pre-eclamptic (PE) women and suitably matched normal pregnant (NP) controls. This was done in order to observe any differences in the pancreatic secretion of insulin between these two groups. Fasting hyperinsulinaemia was observed as a statistically significant feature in the PE. The fasting C-peptide and glucose levels were not significantly different between the two groups. From the fasting C-peptide levels observed it would appear that the hyperinsulinaemia observed in the PE was not the result of hypersecretion of insulin by the pancreas (AU)

The effect of DPT inoculation on the hormonal control of glucose homeostasis in children recovered from malnutrition

The effect of a controlled stress (DPT inoculation) on the hormonal control of glucose homeostasis was investigated in children nutritionally rehabilitated from severe malnutrition. The age range of the 15 children studied was 6-26 months. Plasma insulin (INS), growth hormone (GH) and interleukin-1 (IL-1) were measured by radioimmunoassay; plasma glucose (GLU) by a glucoseoxidase method; and red cell insulin binding ( percentSB) was determined, using A-14 monoiodinated insulin. Measurements were made on two occasions: (T-O) at 10 a.m.,12 hr before DPT inoculation, and (T-36) 36 hr. after inoculation. On both occasions, 4 hr post-prandial blood samples were used, and the mean body temperature(T) on the day of the test was determined. Red cell insulin binding ( percentSB) was significantly higher at T-36 than at T-O (16.8 ñ 1.7 vs 12.1 ñ 1.2 (14), p=0.005). (Results were expressed as mean ñ SEM, numbers of paired observations in parentheses). The higher percentSB after DPT was accompanied by an increase in the number of receptor sites (S) (29.05 ñ 6.5 vs 15.6 ñ 2.5 (14),p=0.025). However, insulin receptor affinity (K x 10(9)M(-1)) was decreased 0.7 ñ 0.1 vs 1.5 ñ 0.3(14), p=0.008). There were no significant differences in the plasma levels of insulin, glucose and interleukin-1, but plasma growth hormone (æU/ml) was increased after DPT, (18.0 ñ 3.0 vs 11.5 ñ 1.2 (13), p=0.04). Body temperature (§C) was also significantly increased after DPT,(99.9 ñ 0.4 vs 98.3 ñ 0.2(14), p=0.006). The change in plasma glucose from T-O to T-36 tended to be associated with both a change in plasma insulin (p=0.06) and plasma growth hormone (p=0.07). Increased insulin binding, as one index of increased insulin sensitivity during fever, can contribute to a reduction in blood glucose. However, the elevation in plasma growth hormone cold buffer the hypoglycaemic effect of insulin, and help to maintain glucose homeostasis (AU)

Ultrastructure of the Islets of Langerhans in protein-energy malnutrition

Significant hormonal changes have been reported in childhood malnutrition, including high serum levels of growth hormone and cortisol, and low levels of circulating insulin. The ultrastructure of the endocrine pancreas in such patients has hitherto not been reported. A light microscopy survey of the pancreatic islets was carried out on 69 malnourished children dying from protein-energy malnutrition. In seven of these cases, a rapid autopsy protocol allowed tissues to be fixed for electron microscopy within 75 minutes of death. This paper presents the first ultrastuctural observations on the Islets of Langerhans in childhood protein-energy malnutrition. In all cases, there was a variable degree of degereration of all cell types with membrane damage, loss of ribosomes, vesiculation and mitochondrial swelling. In addition, the B-cells showed a high proportion of precursor granules compared to crystal forms, possibly accounting for low insulin serum levels reported by other workers. It is suggested that islet cell changes may be related to free radical damage secondary to depletion of glutathione and other antioxidants, as well as relative deficiencies of cysteine and zinc. In addition, the effects of agonal anoxia, and a short fixation delay after death must be considered. (AU)

Changes in red cell insulin receptors during recovery from severe malnutrition

Red cell insulin binding was studied in 13 Jamaican children (age range 4-24 months), while malnourished (MAL), during early recovery (GI), late recovery (GII), and after anthropometric recovery (REC). The rate of weight gain (RW), the energy intake (EN), and the protein intake (PR) were monitored at each phase of the study. Four-hour fasting blood samples were used, and the insulin binding characteristics were investigated in the physiological range of insulin concentrations (16.7-1670 pM). Analyses of variance were used to examine differences in the variables measured at the four phases. Red cell-specific insulin binding (SB) was lower in MAL than in GI (P<0.001) and in (GII) (P=0.026). SB in REC and MAL were not significantly different. Insulin receptor affinity (K) was also lower in MAL than in GI (P<0.001), GII (P<0.001), and REC (P=0.012). The insulin receptor number (S) appeared to be high in malnutrition and to decrease as recovery progressed; however, the decrease was not significant. Children with fever demonstrated high insulin binding. Plasma insulin (IN) rose during recovery, and was significantly higher in GII than in MAL (P=0.01). There was no difference in plasma glucose (G) at any phase of the study. The interrelationships among the variables measured were investigated longitudinally using multiple regression analyses. SB was positively associated with S (P=0.032), EN (P=0.029), and PR (P=0.0076). S was negatively associated with K (P<0.001). The associations of S and K with PR were positive and approached significance (P = 0.09 and P = 0.07 respectively). RW was positively associated with PR (P<0.001), and with EN (P=0.001). There were no significant relationships between G and any of the other variables longitudinally. However, correlations of the variables within phases demonstrated that in MAL, G was negatively associated with SB (P<0.05) and with K (P<0.05); but in REC, G was positively associated with SB (P<0.05). These results demonstrated that in severe malnutrition, the red cell insulin receptor affinity was low. During catch-up growth when protein and energy intakes were increased, both insulin receptor affinity and specific insulin binding were also increased. The negative relationship between insulin binding and plasma glucose during malnutrition may be related to carbohydrate intolerance (AU)

Glucose tolerance in pre-eclampsia - abstract

In normal pregnancies (NP), carbohydrate metabolism as assessed by oral glucose tolerance is impaired. This study was aimed at assessing whether a complication of pregnancy, pre-eclampsia (PE), exacerbates this impairment of carbohydrate metabolism. Results showed that the fasting plasma glucose levels were not significantly different between the PE (4.62ñ0.27 mM/1) and the NP (4.12ñ0.08 mM/1). However, the fasting plasma insulin levels were significantly higher in the PE (28.4ñ5.9 uU/m1) than in the NP (9.6ñ2.3 uU/m1) (p<0.01). Analysis of the area under the curve showed that the glucose response curves were not significantly different. The insulin response curves displayed a trend of higher circulating insulin levels in the PE compared to the NP; (p<0.07). The insulin to glucose ratio, an index of insulin sensitivity, in the PE (6.21ñ1.37) was significantly higher than that of the NP (2.26ñ0.54) p<0.05). We suggest that the hypertensive complication of pregnancy, PE, is accompanied by hyperinsulinaemia in the basal or fasting state, with an accompanying insulin insensitivity (AU)

Plasma somatomedin-C in Nigerian malnourished children fed a vegetable protein rehabilitation diet

Plasma somatomedin-C (pSm-C) was measured by immunoassay in Nigerian malnourished children treated with a mainly vegetable diet. In oedematous children, the mean intake was 4.31ñ0.23 g protein and 611ñ46 kJ per kg body weight per day, and in marasmic children 5.22ñ0.62 g protein and 795ñ131 kJ/kg body weight/d. PSm-C concentration (U/ml) was measured at weekly intervals to determine the response to this rehabilitation diet. By our assay the value for 39 normal children (age range 6-36 months) was 0.315ñ0.035 U/ml. The average initial level of pSm-C in the malnourished children was 0.19ñ0.03 (n=24). The values were higher (P<0.05) in the 7 marasmic children (0.26ñ0.1) than in the 11 with oedema (0.15ñ0.02). Eight days after admission pSm-C had risen to 0.20ñ0.02 (n=24) and at discharge after approximately 19d, pSm-C concentration was normal, 0.30ñ0.05. In oedematous malnutrition, pSm-C level at discharge was lower than in marasmus, 0.27ñ0.06 (n=17) compared with 0.37ñ0.06 (n=7) (P<0.05). Because the childrens' stay in hospital was short (average 19d), they were far from attaining normal weight for height by the time of discharge. However, they had gained on average 0.9 kg and their clinical condition was satisfactory. It is concluded that the vegetable-based diet produced satisfactory recovery, at least in the initial stages. Increases in pSm-C compared well with those found in an earlier study with milk-based diets. (AU)

The effect of diet on plasma somatomedin-C (IGF-I) in Jamaican and Nigerian children recovering from oedematous and non-oedematous malnutrition - abstract

Plasma somatomedin -C (PSm-C) was measured by radioimmunoassay in children with marasmus or kwashiorkor (4-24 months) and during rehabilitation. PSm-C (U/ml) was compared with that of normal children of the same age range (4-6 months, 0.175ñ0.04: 7-12 months, 0.288ñ0.35: 13-18 months 0.289ñ0.120: 19-24 months, 0.598ñ0.160). Initially, Jamaican children were offered one of two isocaloric diets (468J/kg body weight per day), which differed principally in their protein contents A-0.9g:B-3.5/kg body weight per day) at levels which did not permit anabolism. During this phase, oedematous children lost their oedema. They were then offered an energy dense diet (C-1046 KJ and 5.7g protein/kg body weight per day) and gained weight rapidly to achieve the weight of a normal child of the same height. The malnourished Nigerian children were treated with a vegetable-protein based diet which provided a mean intake of 4.3ñ0.2 gm protein and 556+34 KJ/kg body weight per day. PSm-C concentration in both Jamaica and Nigerian children was determined on admission and at weekly intervals during rehabilitation to examine the response to, and hence nutritional adequacy of both types of diets. In Jamaica children, PSm-C was slightly higher in admission but did not differ significantly in marasmic or kwashiorkor children (0.202ñ0.04 (n=9) vs 0.155ñ0.3 U/ml (n=18) respectively). In Nigerian children, PSm-C was higher in marasmic children (0.29ñ0.03 U/ml (n=7) than those with oedematous manutrition (0.15ñ0.03 U/ml (n=18) p<0.05). In both Jamaican and Nigerian children, PSm-C gradually rose after a small initial decline 1 week after admission. In Jamaican children, the increase in PSm-C after 4 weeks in hospital was significantly greater in marasmus than in kwashiorkor (0.431ñ0.71 (n=7) vs 0.269ñ0.05 U/ml (n=16) p<0.01). This difference could be attributed to dietary treatment, since oedematous children were kept from one to three weeks on a maintenance diet (either A or B) until oedema was lost. There was no significant difference in PSm-C on either diet A or B (A-0.165+0021 (n=26). B-0 150+0.019 U/ml (n=29). After 1 week on Diet C, PSm-C was 0.259ñ0.044 (n=21); significantly greater than PSm-C on diet A or B. In Nigerian children, eight days after admission, PSm-C had risen to 0.21ñ0.06 U/ml. In both Jamaican and Nigerian children, after 4 weeks PSm-C rose to normal values for their age range: 0.337ñ0.34 U/ml (n=21) in Jamaican children and 0.30ñ0.07 U/ml (n=25) in Nigerian children. The higher PSm-C shown in marasmic Jamaican children may be related to the early introduction of high energy Diet C (AU)

The relationship of red cell insulin binding to rate of weight gain during recovery from malnutrition - abstract

Chronic nutrient inadequacy, as exemplified by marasmus and kwashiorkor provides a model for insulin-binding studies. Red cell insulin receptors were studies in infants (age range 4 to 24 months) whilst malnourished and at 3 different stages of anthropometric recovery (60-84, 85-95, and 96-110 percent weight-for-height (EWH)). Four-hour fasting blood samples (3 ml) were used. Washed red cells (concentration 0.75 - 1.5x10 Esp 9/ml) were incubated at 15§C for 180 min in the presence of a constant amount of tracer (A[14] - I[125] - insulin, 16.6 - 1680 pM, 7 different concentrations). Non-specific binding was assessed by the radioactive insulin bound in 10,000 x the physiological range of insulin concentration. From the competitive binding curve, total binding, affinity and number of receptor sites were calculated by Scatchard analysis. Specific insulin-binding was expressed as the per cent of total A[14] -I[125]-insulin added at a cell concentration of 4x10Exp9/ml. Red cell specific insulin-binding (SB) in malnutrition (rate of weight change, (RWC) - 2.05ñ1.9 (10) g/kg/d) was 4.2ñ0.8 (12) percent. This was significantly less than at all three phases of recovery (p<0.01). At 60-84 percent EWH(RWC ñ 11.7ñ0.9 (20)), SB was 8.6ñ1.2 (20) percent: at 96 -110 percent EWH (RWC ñ 0.95ñ1.1 (11)), SB was 8.8ñ1.4 (11) percent. A significantly (p<0.01) lower affinity of insulin for its receptor was shown in malnutrition, 0.9ñ0.2 (12) (Kx10Exp-8 M) than at other phases of recovery, 1.8ñ0.1 (24), 1.6ñ0.2 (20), and 1.4ñ0.4 (11) respectively. There were no significant changes in the number of receptor sites during malnutrition or during the catch-up growth phases. There was a highly significant positive correlation between rate of weight change and specific insulin-binding, (r= 0.45, p<0.0001 (67) as compared with plasma insulin concentration (r=0.33, p<0.01). Specific insulin-binding was also significantly correlated with the affinity of insulin for its receptor 9 r=0.28) p<0.05 (67)). Preliminary Results suggest that decreased protein, but not the carbohydrate or fat content of the diet, was associated with reduced insulin receptor affinity. Chronic nutritional inadequacy alters the affinity of the red cell receptor for insulin, leading to decreased binding, and this is quickly reversed early in rehabilitation. Decreased insulin-binding may be related to the carbohydrate intolerance of severe malnutrition (AU)

Free and total triiodothyronine and thyroxine in malnourished Jamaican infants. The effect of diet on plasma levels of thyroid hormones, insulin and glucose during recovery

Plasma concentrations of free triiodothyronine (FT3), total triiodothyronine (TT3) and total thyroxine (TT4) were reduced to 63.0, 37.7, 61.7 per cent of controls respectively in protein-energy malnutrition (PEM), while free thyroxine (FT4) was elevated by 23 per cent. There was a gradual increase of both TT4 and TT3 during recovery. The ratio of free to bound hormones was high in malnutrition and declined with recovery, indicating a deficiency of thyroid-hormone binding in malnutrition. The observation of a significant reduction (P<0.05) in T3/T4 ratios, which occurred in malnutrition and was induced during recovery after 3 d on a low energy maintenance diet, suggested depressed conversion of T4 to T3 due to energy restriction. Energy restriction also significantly (P<0.001) depressed plasma insulin concentrations in the presence of nearly constant glucose levels. (AU)

Fasting pancreatic glucagon in Jamaican children during malnutrition and subsequent recovery

Fasting pancreatic glucagon was observed in Jamaican infants during malnutrition and subsequent recovery. Rehabilitation in two groups of children with isocaloric diets rich either in carbohydrate or fat produced no differences in the rate of weight gain. During malnutrition, plasma pancreatic glucagon concentration was 104ñ11 (n=20) pg/ml (meanñS.E.) significantly lower than during recovery when the maximum value was 180ñ24 (n=13) pg/ml during the later recovery phase. After clinical recovery glucagon levels declined to 127ñ13 (n=15) pg/ml. Plasma insulin followed a similar pattern, increasing significantly during catch-up growth and declining after recovery. Slower rates of growth were associated with the simultaneous decline in the concentrations of both hormones after clinical recovery. (Summary)

Insulin, growth hormone and carbohydrate tolerance in Jamaican children rehabilitated from severe malnutrition

Intravenous glucose tolerance tests were carried out in 20 children (aged 6 - 24 mo) clinically recovered from severe malnutrition. Blood samples were obtained between 10 am and 11 am after 16 hr fast, from a peripheral vein kept patent by a slow infusion of 0.9 percent saline. Samples were taken at timed intervals: 0, 1, 2, 3, 5, 7, 10, 20, 30, 40 and 50 min after IV injection of glucose (0.5 g/kg body weight). Plasma insulin, growth hormone, and glucose were measured. Total responses were expressed as the sum of the values at each time point. The mean rate of glucose removal (KG percent/min) was 2.28 +/- 0.13. This is within the normal published range of 2 to 3.5. Four children were < 1 SD below the mean. In these four children, fasting growth hormone and total growth hormone response were significantly higher (p>0.001) than in the others. There was a wide range for fasting growth hormone: 1-91 uU/ml. There was a negative correlation between KG and total growth hormone response (r = -0.64, p<0.05, n = 12), and between KG and age (r = -0.61, p<0.01, n = 20). In three children fasting glucose was abnormally low. Neither fasting insulin (3.04 +/- 0.33 uU/ml), fasting glucose (3.9 +/- 0.16 mmol/L) nor insulin response were significantly related to KG. Peak insulin was 28.2 +/_ 2.7 uU/ml and peak glucose was 18.5 +/- 0.6 mmol/L. Seven children showed a delayed (5-10 min) insulin response to glucose: 13 had a prompt insulin response 1 min after glucose. The KG of those children who had a delayed insulin response to glucose was normal, but the KG of 2 children with an abnormally low insulin response was below normal. Thus, after anthropometric recovery from malnutrition, 20 percent of children had a low KG, associated with an elevated growth hormone response. In 30 percent of children the insulin response to glucose was delayed, but this was not related to the glucose disappearance rate. In 10 percent of the children, the insulin response to glucose was abnormally low, and this was associated with low KG. In 15 percent of the children, fasting glucose concentrations were abnormally low. Abnormal carbohydrate tolerance was associated with low insulin output and/or elevated growth hormone concentration. (Summary)