B. Persson

Relationship between haemoglobin A1c in early type 1 (insulin-dependent) diabetic pregnancy and the occurrence of spontaneous abortion and fetal malformation in Sweden

SummaryThis prospective nationwide study examined the relationship between diabetic control in early pregnancy as assessed by HbA1C and the incidence of spontaneous abortion and fetal malformation. HbA1C and plasma C-peptide were determined in 532 women with Type 1 (insulin-dependent) diabetes mellitus, corresponding to approximately 80% of all the diabetic pregnancies in the country during the study period 1982–1985, and 222 non-diabetic control women. Median gestational week for sampling was 9.0 in the Type 1 diabetic and 10.0 in the control group. The median value of HbA1C was 7.7% in the diabetic and 5.3% in the control group (p<0.001). The rates of spontaneous abortion, 7.7% vs 7.2%, and malformation, 4.3% (major 2.0%) and 2.4% (major 1.0%), were not significantly different between the diabetic and control group, respectively. These rates of malformation were not significantly different from the national figures of 4.55% (major 1.75%). Much elevated HbA1C, i.e., > 10.1% equal to 8 SD above the normal mean control value, was significantly associated with the occurrence of spontaneous abortion (p<0.001) and malformation (p<0.01). Discriminant analysis revealed that after correction had been made for the significant value of HbA1C to predict the occurrence of spontaneous abortion and malformation, no further predictive power was displayed by measurable plasma C-peptide, maternal age or duration of diabetes or presence of diabetic microangiopathy. We conclude that poor metabolic control in early pregnancy contributes to an increased risk of both spontaneous abortion and fetal malformation.

The Pattern of Blood Lipids, Glycerol and Ketone Bodies during the Neonatal Period, Infancy and Childhood

Studies of individual blood lipid fractions, glycerol, ketones and blood sugar were carried out in a large group of healthy children ranging in age from full term birth to 8 years, with the object of ascertaining the alterations in these parameters at birth and through the period of postnatal adaptation.

Factors influencing the magnitude, duration, and rate of fall of B-cell function in type 1 (insulin-dependent) diabetic children followed for two years from their clinical diagnosis.

SummaryThe pattern of fall in B-cell function measured as plasma and 24 h urinary C-peptide excretion, as well as levels of islet cell antibodies, insulin antibodies and metabolic parameters, were followed for two years in 39 children aged 1–17 years prospectively from clinical onset of Type 1 (insulin-dependent) diabetes. At onset 32/36 patients had measurable plasma C-peptide (median 0.13 nmol/l). Maximum values of fasting and postprandial plasma C-peptide were reached at a median duration of three months. Thereafter both plasma and urinary C-peptide declined linearly. The median value of the rate of fall in postprandial plasma C-peptide was 0.019 nmol·1−1·month−1. Age at onset was positively correlated to the maximum value of postprandial plasma C-peptide in each patient (rs=0.57, p=0.0001) and throughout the observation time positively correlated to fasting and postprandial C-peptide and to the 24 h urinary C-peptide excretion (rs range 0.35–0.70, p=0.03–0.0001). The rate of fall of postprandial C-peptide was unrelated to age at onset and was strikingly parallel in different age groups. Islet cell antibodies were present in 87% of the patients at onset and decreased to 38% at 24 months. Islet cell antibody litres were not correlated to age at onset or to plasma or urinary C-peptide at any single observation. However, islet cell antibody negative patients had significantly higher (p<0.05) postprandial plasma C-peptide values at 1, 9, and 12 months of duration, compared to islet cell antibody positive patients. Insulin antibodies and metabolic state at onset did not influence the C-peptide values. It is concluded that age at onset is the most important variable in predicting the duration and magnitude of endogenous insulin secretion during the first two years of Type 1 diabetes in children.

CEREBRAL BLOOD FLOW AND EXCHANGE OF OXYGEN, GLUCOSE KETONE BODIES, LACTATE, PYRUVATE AND AMINO ACIDS IN ANESTHETIZED CHILDREN

Abstract. Settergren, G., Lindblad, B. S. and Persson, B. (Department of Paediatrics, Karolinska Institutet and the Unit of Paediatric Anesthesiology, St. Görans Hospital, Stockholm, Sweden). Cerebral blood flow and exchange of oxygen, glucose, ketone bodies, lactate, pyruvate and amino acids in anesthetized children. Acta Paediatr Scand, 69: 457, 1980.—Cerebral blood flow (CBF) and cerebral av differences of oxygen, glucose, 3‐hydroxybutyrate, acetoacetate, lactate, pyruvate and amino acids were measured in anaesthetized children before elective surgery in order to study possible age‐dependent variations. CBF was measured in 70 children, aged 11 days to 15 years. Cerebral av differences were studied in approximately 50% of the subjects. Mean values were: CBF 0.65 ml X g‐1 X min‐1, cerebral exchange in nmoles Xg‐1 X min‐1: oxygen 1348, glucose 248, acetoacetate 12,3‐hydroxybutyrate 34 (uptake), lactate‐48, pyruvate‐8 (release). No net exchange of amino acids was found with the exception of histidine (uptake). Neither CBF nor the cerebral exchange of oxygen and circulating substrates showed any correlation to age within the group. Compared with adults anesthetized by the same technique (barbiturate induction, nitrous oxide‐oxygen relaxant) the children had a slightly higher mean CBF, while the cerebral up‐take of oxygen and glucose were equal to values in adults. The cerebral uptake of ketone bodies was higher in children than reported values in adults investigated in the awake state after comparable periods of fasting.

Follow‐up of Children of Insulin‐dependent and Gestational Diabetic Mothers: Neuropsychological Outcome

ABSTRACT. Ninety‐four infants of 28 weeks gestation or more were born to 85 women, 64 type I and 21 gestational diabetics, between 1969–1972 at Sabbatsbergs Hospital, Stockholm. Perinatal mortality rate was 6.3%. The follow‐up study was conducted when the children were approximately 5 years of age and included a physical and a neurological evaluation, IQ determination of mother and child, and an interview of mother by a psychologist. Fifty‐three infants of insulin‐dependent (IDM) and 20 infants of gestational diabetic mothers (IGDM) (83 %) participated, 3 families could not be traced and 12 were unwilling. The group lost to follow‐up (13 IDM, 2 IGDM) had more perinatal complications induding congential malformations than the follow‐up group. All children had normal physical and neurological development. IQ was normal, the majority were above 100, the average in IDM was 115 (range 89–144) and 112 in IGDM (range 95–133). No obvious relationship was found between maternal acetonuria during pregnancy, infant birthweight, blood glucose during first hours after birth or neonatal complications and IQ of the children. A correlation (r= 0.364, p<0.01) was found between maternal and child IQ. Mothers exhibiting emotional disorders (anxiety, depression) had significantly higher life stress scores based on 29 stress variables and reported more frequently about conduct and behavioural disorders in their children than mothers without emotional disturbances.

Follow-up of children of insulin dependent (type I) and gestational diabetic mothers. Growth pattern, glucose tolerance, insulin response, and HLA types.

ABSTRACT. Fifty‐three children of insulin dependent (IDM) and 20 children of gestational diabetic mothers (IGDM) representing 80 and 91 %, respectively, of all surviving infants of diabetic mothers born between 1969 and 1972 at Sabbatsbergs hospital, Stockholm, participated in the follow‐up study. The first follow‐up examination was performed when the children had reached approximately 5 years of age and included measurement of height and weight, insulin response to intravenous glucose, and HLA typing. When the children were approximately 11 years old, a search was performed in the national register for type I diabetes in children in order to ascertain the frequency of type I diabetes mellitus in the total series (n=88). The majority of children had a normal height for age and desirable weight for height. At the first follow‐up all children had normal glucose disappearance rates (kt) and the insulin response including the early insulin response to glucose were not different between IDM and IGDM groups. The frequency distribution of HLA antigens (A, B, C) was not different from normal and there was no association between HLA B 8 and/or B 15 and early insulin respone or kt values. At the second follow‐up, two children of type I diabetic mothers had acquired type I diabetes, both were HLA B 15 positive, had normal kt values at the first follow‐up, one with low, one with a high early insulin response. The frequency of type I diabetes in offspring of insulin dependent diabetic mothers was 3%.

Plasma Amino Acids in Relation to Metabolic Control in Insulin-Dependent Diabetic Children

ABSTRACT. The influence of metabolic control (estimated by blood glucose, 3‐hydroxybutyrate and glycosylated hemoglobin levels) on plasma amino acids was determined in a group of 56 insulin‐dependent diabetic children. A multiple correlation analysis revealed significant positive partial correlations between most amino acids and blood glucose. Alanine, methionine, tyrosine, phenylalanine and arginine showed negative partial correlations to the 3‐hydroxybutyrate level. The results are consistent with the postulate that ketone body inhibition of muscle proteolysis is one of the factors regulating substrate flows during insulin deficiency.

Reduction of protein intake decreases glomerular filtration rate in young Type 1 (insulin-dependent) diabetic patients mainly in hyperfiltering patients

SummaryThe influence of different protein intake on renal function was studied in 16 Type 1 (insulin-dependent) diabetic patients, aged 15–23 years, with onset of diabetes before puberty and with a duration of diabetes between 5 and 20 years. The glomerular filtration rate, renal plasma flow, albumin excretion rate, and blood pressure were examined in a cross-over randomised order after 10 days on isocaloric diets with either 10% (i.e. 0.9±0.06 g·kg−1·day−1) or 20% (1.9±0.1 g·kg−1·day−1) of the calories as protein, the latter being equal to the recommended diet. Dietary compliance was evaluated using fractional phosphate excretion and overnight urea excretion. Glomerular filtration rate was lower after the low-protein diet compared to the usual protein diet (p<0.001). Patients with glomerular filtration rate above +2 SD of the normal mean on the usual protein diet (n=6) exhibited the steepest fall in glomerular filtration rate with a mean decrease of 20ml/min compared to 7 ml/min in those with initially normal glomerular filtration (p=0.01). Filtration fraction tended to decrease on low protein diet, more so in initially hyperfiltering patients (p=0.09). Renal plasma flow remained unchanged. In patients with elevated glomerular filtration rate on usual protein diet, albumin excretion rate and systolic, but not diastolic blood pressure, were decreased on low protein diet (p=0.03 and p=0.01, respectively) but not in initially normal-filtering patients. Mean blood glucose and serum fructosamine were unchanged on both diets. In conclusion, low protein diet decreases glomerular filtration rate independently of glycaemic control in young Type 1 diabetic patients and more so in hyperfiltering patients. This decline in glomerular filtration rate is accompanied by a decrease in albumin excretion rate and systolic blood pressure in hyper-filtering patients.

Effect of feeding on intravenous glucose tolerance and insulin response in piglets during the first day of life

Abstract The influence of postnatal age and nutritional status on the disappearance rate of glucose (k G value), the insulin response and the changes in plasma free fatty acids and glycerol following an intravenous glucose load have been studied in 37 piglets during the first 24 hours of life. Groups of fed and starved animals were studied at 1−1 1 2 , 7–12 and 16–24 hours of age. A group fed 4 hours and subsequently starved for 20 hours was also studied. In fed piglets there was a rise in k G value accompanied by a marked increase in insulin response during the first day of age. In starved animals there was no change in k G value with age and only the oldest age group showed an increase in insulin response, less than that seen in fed animals. The fed-starved group had k G values similar to fed animals and insulin responses intermediate between those of fed and starved animals of comparable ages. The plasma free fatty acid and glycerol concentrations were low in all groups of piglets and showed only minimal changes following the glucose load. The results indicate that in the piglet the increase in k G value during the first day of life is dependent on food intake rather than on age. Although the insulin response following an intravenous glucose load improves with age, it is markedly augmented by feeding.

Blood lipids in diabetic and non-diabetic schoolchildren.

The fasting blood levels of cholesterol, phospholipids, glycerides and free fatty acids (79 cases only) were determined in a group of 7–20‐ year‐old school children, consisting of 137 diabetics and 121 matched non‐diabetic controls.