Increase in insulin antibodies during continuous subcutaneous insulin infusion and multiple-injection therapy in contrast to conventional treatment.

Forty-five insulin-dependent diabetics were randomized to 1 yr treatment with either continuous subcutaneous insulin infusion (CSII), multiple insulin injections (MI), or continued conventional treatment. The CSII group used regular insulin only, the MI group used 4-6 premeal injections of regular insulin and intermediate insulin at night, and the conventional group used two daily injections of combined regular and intermediate insulin. Only highly purified porcine insulin was used. Near normoglycemia was obtained during CSII and MI but not during conventional treatment. Antibodies against insulin were measured in serum samples by measuring the binding of iodinated porcine insulin to serum after removal of free and antibody-bound insulin from the samples by acid charcoal. The percent binding of 125I-labeled insulin increased significantly during MI and CSII, in contrast to conventional treatment. Nineteen patients had sufficient binding capacity for Scatchard analysis. In the CSII and MI groups, high- or low-affinity antibodies or both were induced. When insulin was administered subcutaneously during MI or CSII for 1 yr, the insulin antibody production increased, in contrast with conventional treatment.

The effect of cooking upon the blood glucose response to ingested carrots and potatoes.

Ten insulin-dependent diabetic subjects were given the following tests in randomized order: 50 g glucose dissolved in water, 250 g raw and cooked potato (equal to 50 g carbohydrate), 270 g raw and cooked carrot (equal to 25 g carbohydrate), and 4 h of fasting. Blood glucose was measured for 4 h following the tests. The postprandial blood glucose responses after pure glucose and cooked potato were almost similar (90-min values: glucose 8.8 mmol/L, cooked potato 8.0 mmol/L), while the response after raw potato was considerably slower and weaker (90-min value: 3.3 mmol/L). There were no differences between the postprandial blood glucose responses after raw and cooked carrot (90-min values: raw carrot 3.2 mmol/L, cooked carrot 2.8 mmol/L), but the responses were statistically different from blood glucose values during fasting alone (90-min value: 0.8 mmol/L). The study shows that cooking is responsible for the rapid increase in blood glucose after ingestion of cooked potato, while no such phenomenon is seen after cooking of carrots.

Homozygous mutation (A228T) in the 5alpha-reductase type 2 gene in a boy with 5alpha-reductase deficiency: genotype-phenotype correlations.

The molecular basis of a patient with 5alpha-reductase deficiency was investigated in this study. This disease is a rare form of male pseudohermaphroditism with virilization during puberty. The child was raised as a girl, but had a male gender identity early in life. The diagnosis was set at the age of 13 years when the virilization process began. Hypospadias repair was performed and he changed to a male gender. DNA sequence analysis disclosed a homozygous mutation in exon 4 of the 5alpha-reductase type 2 gene, alanine 228 for threonine. The heterozygous parents are first cousins of Pakistani origin.

Plasma glucose and insulin responses to orally administered carbohydrate-rich foodstuffs.

Healthy individuals were given different carbohydrate-rich test meals (each with an energy content of 300 kcal) after a standardization period. Plasma glucose and insulin were measured during the tests. When compared with an ordinary oral glucose load, potato had a post-prandial plasma glucose and insulin response not statistically different from the glucose load, the bread group had a weaker and slower response than the potato group, and rice had a response between the two other groups. Gastric emptying, the availability of the starch for digestion and differences in the carbohydrate content are discussed as possible explanations for these differences.

Screening for cystic fibrosis among newborns in Norway by measurement of serum/plasma trypsin-like immunoreactivity. Results of a 2 1/2-year pilot project.

A pilot project for neonatal screening for cystic fibrosis (CF) by measuring trypsin-like immunoreactivity (TLI) in liquid serum or plasma samples was carried out in Norway from May 1982 to December 1984. A total of 72,320 newborns was screened. Twelve infants were recalled for sweat testing; 11 were confirmed to have CF. One infant had normal sweat sodium and chloride levels and no clinical symptoms. The incidence of CF in this study was 1:6574, and the recall rate for second blood samples was 0.6%. No false-negative cases have yet been reported. The level of TLI was affected by the use of heparin in plasma preparation, being reduced by about 20% as compared to serum levels.

[Hereditary intrahepatic cholestasis with lymphedema--Aagenaes syndrome]. / Arvelig intrahepatisk gallestase med lymfødem--Aagenaes' syndrom.

Hereditary intrahepatic cholestasis with lymph oedema is now a well defined autosomal recessive inherited syndrome. More than 75% of the known cases (about 40) are Norwegian, and most of these came from a few communities in the south-western part of Norway. Cholestasis is present prior to or shortly after birth. With modern treatment the cholestasis usually improves considerably during the first two years of life, but periods of recurrent cholestasis occur later. In some cases, lymph oedema is present at birth, but usually comes to light during childhood. Lymph oedema needs continuous treatment. As a rule, the prognosis for the liver disease is good, but cirrhosis has developed in about 15% of the Norwegian cases. As for the pathogenesis of the cholestasis, the hypothesis is that the cause is an anomaly of the lymph function.

Diabetic complications in a prepubertal adolescent.

A 13 year old boy, with a five year history of diabetes mellitus, developed a severe neuropathy and a transient deterioration of a background retinopathy after initiation of improved glycaemic control. This followed a long period of extremely poor metabolic control, with growth retardation and weight loss.

Increase in blood glucose in insulin-dependent diabetics after intake of various fruits.

The increase in blood glucose in insulin-dependent diabetics after different fruit meals was investigated. Apple, banana and orange loads were compared with an equal amount of glucose dissolved in water. The postprandial blood glucose responses to pure glucose, apple and banana were almost identical, while the response after orange was somewhat weaker. We therefore conclude that though these fruits contain considerable amounts of fructose, they represent an important source of rapidly absorbable carbohydrate and should mainly be used in mixed meals.

Effect of different kinds of fibre on postprandial blood glucose in insulin-dependent diabetics.

Dietary fibre may retard glucose absorption in normal and diabetic subjects. It is, however, unclear which type of fibre would be most suitable for this purpose. We therefore studied whether pectin differs from fibre from barley (85%) and citrus (15%) (Dumovital) in its effect on postprandial blood glucose responses. Eight insulin-dependent diabetics fasted overnight and were then given a meal without their morning insulin. The basic meal, composed of 90 g white bread and 120 g jam (total carbohydrate 105 g), was given three times: alone, with 15 g pectin and with 15 g Dumovital fibre. Blood glucose was measured for three hours. The tests showed that pectin administration considerably inhibited the postprandial rise in blood glucose, while Dumovital showed no such effect. Barley/citrus fibre (a mixture of cellulose, hemicellulose, lignin and pectin) has not the same inhibiting effect on postprandial rise in blood glucose as pure pectin in insulin-dependent diabetics. Thus, the specific type of fibre must be considered when prescribing dietary fibre to diabetics.

Sucrose and sorbitol as sweeteners in the diet of insulin-dependent diabetics.

Blood glucose levels following breakfast meals containing sorbitol or sucrose as sweeteners were investigated. Nine insulin-treated diabetics received two test meals after an overnight fast. The meals were composed of 90 g white bread, 9 g butter and 100 g strawberry jam which on one occasion contained 18 g sorbitol as sweetener and on another 18 g sucrose. Blood glucose was measured for three hours following the meal. The test meal sweetened with sucrose showed a slightly faster postprandial rise in blood glucose than the sorbitol-sweetened meal, but this difference is not statistically significant at any point of the curves. Taking into consideration that sorbitol has a sweetening effect of only 60% of that of sucrose, we conclude that neither sucrose nor sorbitol are acceptable sweeteners for insulin-dependent diabetics.

Cholestatic jaundice in infancy. The importance of familial and genetic factors in aetiology and prognosis.

One hundred and twenty-four infants admitted to hospitals in Norway between 1955 and 1974 during the first 3 months of life with cholestatic jaundice were studied retrospectively. Sixty-four infants had had extrahepatic atresia of the biliary tree and 60 had had intrahepatic cholestasis. This gives an incidence of about 1:9000 live births for cholestasis. In 4 of the 64 infants with extra-hepatic atresia a bile duct-to-bowel anastomosis had been performed but this was successful in only 2. Sixty of these infants had died by their 2nd birthday. Twenty-six of the infants with intrahepatic cholestasis had died by 1978 and the most common causes of death were cholestasis complicated by infection, bleeding, or hepatoma. The survivors aged between 4 and 23 years were followed up in 1978. In about two-thirds of them aetiological factors--such as alpha-1-antitrypsin deficiency, arteriohepatic dysplasia, cholestasis with lymphoedema--and other familial or genetic factors, or infections were found. Four of the 34 survivors are known to have cirrhosis. Twenty patients had biochemical abnormalities, and 12 had normal liver function tests. Two patients could not be examined. Of the 19 patients with familial or genetic aetiological factors, 4 had cirrhosis, 14 had biochemical abnormalities, and only 5 had normal liver function tests. Of 11 survivors with idiopathic disease or septicaemia, none had cirrhosis and only 4 had abnormal liver function tests.

Reduction of urinary albumin excretion after 4 years of continuous subcutaneous insulin infusion in insulin-dependent diabetes mellitus. The Oslo Study.

Urinary albumin was studied in 45 patients with insulin-dependent diabetes in a 4-year prospective randomized trial, comparing continuous sc insulin infusion (CSII), multiple insulin injections, and conventional treatment with twice daily injections. Strict blood glucose control was obtained with CSII and multiple injections, better than with conventional treatment (2P less than 0.01): mean glycosylated haemoglobin (% HbA1 +/- SEM) after 4 years: CSII 9.0 +/- 0.4%; multiple injections 9.4 +/- 0.4%; conventional treatment 10.5 +/- 0.5. A total of 696 24-h urine specimens were collected. After 4 years of CSII from the time of randomization, urinary albumin excretion was reduced (26 +/- 5 to 16 +/- 4 mg/24 h, mean +/- SEM, 2P less than 0.01), when compared with conventional treatment (2P = 0.01), when compared with conventional treatment (2P = 0.01) where no change was observed (21 +/- 4 to 22 +/- 6 mg/24 h, n.s.). The reduction observed during multiple injection treatment was not significant (17 +/- 3 to 14 +/- 3 mg/24 h). Long-term near-normoglycaemia may influence the mechanisms leading to albuminuria in diabetes, if introduced at an early stage of the disease.

Microalbuminuria is associated with long term poor glycemic control in adolescent insulin dependent diabetics.

In insulin dependent diabetics microalbuminuria predicts proteinuria which is associated with an extremely high relative mortality rate. We studied the connection between long term blood glucose levels and microalbuminuria. One hundred and twenty-seven patients between 10-20 yr of age were screened for microalbuminuria. Twenty patients with both persistent microalbuminuria (greater than 15 micrograms/min albumin in at least two out of three timed overnight urine samples) and greater than 4 measurements of glycosylated hemoglobin A1 yearly for 5 yr, were included in the study. These 20 patients were matched with respect to sex, age and duration of diabetes against the normoalbuminuric diabetics. The patients with microalbuminuria had significantly higher mean 5-yr glycosylated hemoglobin A1 values than those with normoalbuminuria, 12.4 and 10.5% respectively (p less than 0.01). The data indicate a logarithmic association between mean 5 yr glycosylated hemoglobin A1 values and the urinary albumin excretion rate. The study points to a strong association between long term blood glucose levels and microalbuminuria in adolescents.

The effect of exercise on diabetic control and hemoglobin A1 (HbA1) in children.

14 children with juvenile diabetes mellitus (mean age 11 years, mean diabetes duration 5 years) were enrolled in a one-hour twice weekly supervised exercise program for 5 months. A group of 8 diabetic children of same age and diabetic duration served as control group. Maximum oxygen uptake was within normal range for all children. With this exercise program the maximum oxygen uptake of the training group did not change significantly compared with the control group. The physicians rating of degree of the metabolic control based on blood-glucose measurements and urinary glucose excretion did not change in any of the groups. The insulin dosage per kilo body weight remained unchanged in both groups. In the training group the HbA1 values decreased during the exercise period from 15.1 +/- 2.2 (mean HbA1 % +/- 1 S.D.) to 13.8 +/- 1.9 (2p less than 0.001). In the control group the HbA1 values did not change significantly (13.4 +/- 1.9 to 12.9 +/- 1.6; 2p = 0.20). In a co-study the effect of freezing and storage of hemolysates, resulting in increased levels of HbA1, was demonstrated.

Continuous subcutaneous insulin infusion (CSII), multiple injections (MI) and conventional insulin therapy (CT) in self-selecting insulin-dependent diabetic patients. A comparison of metabolic control, acute complications and patient preferences.

Continuous subcutaneous insulin infusion (CSII) and multiple injections (MI) have been shown to have metabolic advantages in highly-selected insulin-dependent diabetics (IDDs), but there have been few comparative studies in self-selected IDDs. With MI, the optimal insulin preparation for overnight insulin delivery has not been defined. We compared conventional 2-3 injection therapy (CT), CSII and MI with human isophane insulin (MI/human isophane) and human ultralente insulin (MI/human ultralente), respectively, at bedtime in self-selected IDDs. Of 275 IDDs who were invited to participate, 52 individuals (18.9%) entered the study. Most indices of glycaemic control showed better values on CSII and also on MI compared to CT, but the differences were small. Fasting blood glucose was higher on MI/human ultralente than on MI/human isophane. Only one subcutaneous abscess and one case of ketoacidosis requiring hospitalization occurred on CSII. Serious hypoglycaemic episodes were non-significantly increased on intensified therapy. Most patients clearly preferred intensified insulin therapy; approximately one half CSII.

Hereditary cholestasis combined with peripheral pulmonary stenosis and other anomalies.

A syndrome consisting of chronic intrahepatic cholestasis with retention of bile acids but with normalization of bile pigment excretion ahd blood lipids, peripheral pulmonary stenosis, vertebral anomalies and a characteristic facies is described in six patients, including a father and his daughter. An autosomal dominant mode of inheritance is suggested.

[Familial hypercholesterolemia in children. A management program. Procedures for diagnosis and treatment in our pediatric departments]. / Familiaer hyperkolesterolemi hos barn. Handlingsprogram prosedyrer til diagnostisering og behandling ved våre barneavdelinger. Gruppen som har utarbeidet handlingsprogrammet er nedsatt av Norsk barnelegeforening, 1995.

A Norwegian programme for treatment and selective screening of familial hypercholesterolaemia has been developed which takes into account family history and levels of hypercholesterolaemia. The programme includes recommendations on when and whom to screen for familial hypercholesterolaemia. With regard to treatment, special emphasis is placed on diet. The working group suggests that small lipid clinics with a dietitian should be established in some paediatric departments.

Rapid tightening of blood glucose control leads to transient deterioration of retinopathy in insulin dependent diabetes mellitus: the Oslo study.

In a study of retinopathy during one year of tight blood glucose control 45 type I (insulin dependent) diabetics without proliferative retinopathy were randomised to receive either continuous subcutaneous insulin infusion, multiple insulin injections, or conventional insulin treatment (controls). Near normoglycaemia was achieved with continuous infusion and multiple injections but not with conventional treatment. Blind evaluation of fluorescein angiograms performed three monthly showed progression of retinopathy in the control group, transient deterioration in the continuous infusion group, and no change in the multiple injection group. Half the patients receiving continuous infusion and multiple injections developed retinal cotton wool spots after three to six months. These changes regressed in all but four patients after 12 months. Control patients did not develop cotton wool spots. Patients who developed cotton wool spots are characterised by a larger decrement in glycosylated haemoglobin and blood glucose values, more frequent episodes of hypoglycaemia, a longer duration of diabetes, and more severe retinopathy at onset. A large and rapid fall in blood glucose concentration may promote transient deterioration of diabetic retinopathy.

Elevated albumin excretion rate is common among poorly controlled adolescent insulin dependent diabetics.

We studied urinary albumin excretion in 2 different groups of teenage diabetics, one with HbA1 less than 10% (n = 15) and another with HbA1 greater than 13% (n = 17). We found a highly significant difference between the 2 groups regarding the albumin excretion rate (AER) in overnight urines. Median value 15.8 micrograms/min (range 4.9-80.5) and 4.2 micrograms/min (range 1.0-12.6) in the high and low HbA1 group respectively. In a reference group of 19 healthy teenagers, the median AER was 4.9 micrograms/min (range 0.5-15.0). 59% of the patients in the high HbA1-group had values above the upper range in the reference group, 15 micrograms/min, and one had positive Albustix. In contrast, no difference in AER was observed between the low HbA1-group and the reference group. We did not find any correlation between AER and duration of diabetes, but the one patient with gross proteinuria had had diabetes for 14 years. No significant difference between the groups regarding blood pressure or retinopathy was found. Thus, AER was elevated in a large proportion (59%) of poorly regulated diabetic teenagers regardless of diabetic duration. This fact questions the value of employing moderately elevated urinary albumin excretion rate in teenage diabetics as a marker for later development of clinical diabetic nephropathy.

Sorbitol as a sweetener in the diet of insulin-dependent diabetes.

UNLABELLED: We compared sorbitol given alone and as part of a mixed meal to nine insulin-dependent diabetics (IDD's) during continuous subcutaneous insulin infusion (CSII). Blood glucose, sorbitol and breath hydrogen + methane were measured following six test meals: Pure glucose, sorbitol and lactulose, a mixed meal alone, and sweetened with sorbitol and sucrose. Blood glucose increase was very small after lactulose and sorbitol, significantly larger after glucose. A considerable increase in breath hydrogen + methane appeared after sorbitol and lactulose, but not after glucose. No differences in blood glucose responses were found after the mixed meal alone or sweetened with sorbitol and sucrose. A sustained low level increase in breath hydrogen + methane occurred after all solid meals. Sorbitol was not detected in serum after any meal. CONCLUSION: Sorbitol ingested by IDD's during CSII in watery solution is not absorbed in the small intestine and causes osmotic diarrhoea. Ingested in a composite meal it does not affect blood glucose and does not cause osmotic diarrhoea.