Autoimmune (type 1) diabetes in young adults in Sweden.
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Adolescent↗
Biomedical subjects
H Arnqvist
Publications and source records attributed to H Arnqvist.
Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia.
We report five novel mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism. Each gene defect is a missense mutation (228Arg-->Gln, 139Thr-->Met, 144Gly-->Glu, 63Arg-->Met, and 67Arg-->Cys) that encodes a nonconservative amino acid alteration. These mutations are each predicted to be in the Ca(2+)-sensing receptor's large extracellular domain. In three families with FHH linked to the Ca(2+)-sensing-receptor gene on chromosome 3 and in unrelated individuals probands with FHH, mutations were not detected in protein-coding sequences. On the basis of these data and previous analyses, we suggest that there are a wide range of mutations that cause FHH. Mutations that perturb the structure and function of the extracellular or transmembrane domains of the receptor and those that affect noncoding sequences of the Ca(2+)-sensing-receptor gene can cause FHH.
Calcium↗
Nutritional assessment and muscle energy metabolism in severe chronic congestive heart failure--effects of long-term dietary supplementation.
In order to investigate nutritional status in relation to the metabolic state of skeletal muscle in patients with severe congestive heart failure, and to explore the influence of long-term dietary supplementation, 22 patients were randomized in a double-blind study to receive either a placebo (n = 13) or high caloric fluid (n = 9). Before treatment, the muscle content of adenosine triphosphate (ATP), creatine and glycogen was lower than in healthy individuals, and muscle biopsies revealed an excess of water. Two patients were found to be malnourished according to nutritional assessment criteria. Following study treatment, no significant changes occurred, either within or between the two subgroups. Thus, patients with severe congestive heart failure displayed metabolic derangement in skeletal muscle which did not seem to be explained by malnutrition.
Aged↗
No pharmacokinetic effect of retaining the infusion site up to four days during continuous subcutaneous insulin infusion therapy.
This study was designed to investigate whether the indwelling time of the needle during continuous subcutaneous insulin infusion (CSII) could contribute to one of the main problems with subcutaneous insulin administration, that is the day-to-day intra-patient variation in absorption. The effect on insulin kinetics after a bolus dose was investigated at different time intervals up to 4 days after insertion of an indwelling catheter in situ for CSII therapy. Nine insulin-dependent diabetic patients treated with pump (Nordisk Infuser; Velosulin 100 U ml-1) took part in the study. The evening before day 1 of the investigation a needle connected to the pump with a polyethylene catheter was inserted subcutaneously on the abdominal wall where it remained throughout the investigation. There were no significant differences in blood glucose or plasma free insulin profiles between days 1, 3, and 5. The intra-patient coefficient of variation of free insulin was 38% at basal and 19% at post-bolus state. We conclude that during CSII it is acceptable from a pharmacokinetic point of view to retain the infusion site for up to 4 days.
Adult↗
Risk of developing insulin-dependent diabetes mellitus (IDDM) before 35 years of age: indications of climatological determinants for age at onset.
This study analyses data from two nationwide prospective diabetes registries now covering about 3400 cases from 19 million person-years of follow-up in the age group 0-34 years. The risk of developing insulin-dependent diabetes mellitus (IDDM) per 100,000 individuals before 15 years was 386 (95% confidence intervals (CI): 362-410) for boys and 391 (95% CI: 367-415) for girls and by 35 years 701 (95% CI: 671-731) for men and 562 (95% CI: 534-690) for women. The incidence rate showed a maximum for both boys and girls in early puberty. After pubertal years a sharp increase in the male to female incidence ratio of IDDM was notable. At 10-14 years it was 0.94, at 15-19 years 1.59 and at 20-24 years 2.08. A Cox regression model was used to analyse the effects on age at onset of sex, population density and climatological factors as measured by north-south area of residence and season at onset. The effect of sex was confirmed (P less than 0.001). A significant effect (P = 0.004) of season was shown when the four seasons were classified according to a four stage scale related to mean temperature. When dividing Sweden into 11 regions according to north-south gradient (Latitude 55 degrees, 56 degrees, 57 degrees, ..., 65 degrees) a significant effect (P = 0.038) was also found. However, no effects of population density or living near the coast versus in the interior were found. It is concluded that a large proportion of the young are at risk of developing this chronic disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Insulin-like growth factor I in initial renal hypertrophy in potassium-depleted rats.
We investigated insulin-like growth factor I (IGF-I) in the kidney during the initial renal enlargement induced by dietary K depletion in rats. Kidney weight increase was significant after 3 days of K depletion and amounted to 29% after 7 days compared with pair-fed controls [839 +/- 34 vs. 648 +/- 17 mg (SE), P less than 0.01]. The kidney growth occurred despite almost complete arrest in body weight gain in K-depleted animals (8 +/- 3 vs. 34 +/- 4 g/7 days in controls, P less than 0.01). Whole kidney protein, RNA, and DNA estimations indicated that cellular hypertrophy during the first 4 days was followed by hyperplasia. Immunoassayable kidney IGF-I concentration increased by 106% (673 +/- 30 vs. 327 +/- 14 ng/g, P less than 0.01) in K-depleted animals 24 h after induction of K depletion, stayed elevated until day 4, and returned to control levels on day 7. After K depletion for 24 h, IGF-I immunostaining was markedly increased in the medullary parts of the collecting ducts from K-depleted animals, whereas kidney IGF-I gene expression (IGF-I mRNA) had decreased by 36%. The increase in total kidney IGF-I concentration and immunostainable IGF-I in collecting ducts in kidneys from K-depleted rats precedes the renal hypertrophy and thereby suggests a renotropic role for IGF-I. The increase in kidney IGF-I concentration is not associated with increased IGF-I mRNA levels, indicating that non-transcriptional mechanisms may be responsible for the renal IGF-I accumulation.
Animals↗
Pre- and postprandial hyperinsulinemia during insulin pump treatment; role of the subcutaneous bolus and basal infusion.
The impact of the bolus dose and the basal infusion during insulin pump treatment on pre- and post-prandial hyperinsulinemia was investigated in 8 insulin-dependent diabetic patients. Frequent determinations of free insulin in blood and simultaneous determination of glucose consumption with euglycaemic clamp technique were made after a bolus of 5 U with or without basal infusion and after 10 U with basal infusion. The maximum free insulin level was reached after 75, 65 and 105 min respectively (median; NS), whereas 50% of the maximum was reached already after 15, 10, and 12.5 min (NS). The fall in free insulin after the peak was slower in all protocols compared to the breakfast induced peak in healthy subjects and it was slower with than without basal infusion (p less than 0.03). Glucose consumption followed the free insulin profiles. We conclude, that administration of a subcutaneous bolus with an insulin pump gives a dose-related free insulin peak that is unphysiological in comparison with the normal meal-related insulin secretion. Preprandial hyperinsulinemia, found after a prescribed interval of 30 min between injection and meal, as well as postprandial hyperinsulinemia, increased with a greater bolus indicating that adjustments of timing of meals and snacks may be necessary when the dose is changed. Furthermore, the insulin substitution with external pumps would probably be more physiological if the basal supply was interrupted after a bolus.
Adult↗
Familial hypocalciuric hypercalcaemia: a study of four kindreds.
Four kindreds with hereditary hypercalcaemia have been investigated. Thirty-seven of 72 subjects examined had hypercalcaemia with an autosomal dominant pattern of inheritance. Hypercalcaemic patients had total serum calcium of 2.91 +/- 0.12 mmol l-1. Serum parathyroid hormone (PTH) was normal while daily urinary calcium excretion was subnormal (below 2.5 mmol) in 45%. Comparison with an age-matched group of patients with primary hyperparathyroidism gave a small overlap regarding serum human PTH, urinary calcium and the ratio between calcium clearance and creatinine clearance. Family screening therefore is of diagnostic importance. Twelve subjects had been subjected to parathyroid surgery before the correct diagnosis was settled, none of the cases had an adenoma. Three patients became normocalcaemic and the others had persistent hypercalcaemia. One male non-abuser had seven episodes of acute pancreatitis before surgery and none after. The findings in all four kindreds are compatible with familial hypocalciuric hypercalcaemia (FHH). This hereditary disorder of unknown aetiology, therefore, also exists in Scandinavia. It is of importance to consider FHH in the differential diagnosis of hypercalcaemia, since this disorder usually has a benign prognosis if untreated.
Calcium↗
Free and total insulin as determined after precipitation with polyethylene glycol: analytical characteristics and effects of sample handling and storage.
We evaluated results of radioimmunoassays of free and total insulin after precipitation of endogenous antibodies with polyethylene glycol (PEG), and we investigated the influence of collection time, temperature, and storage in heparin- cr EDTA-treated plasma or serum on results for free insulin. Analytical recovery of free insulin was 99.3%, of total insulin 96.4%. For free insulin, assay precision (CV) was 4.0-13.0% (intra-assay) and 7.8-10.7% (inter-assay); for total insulin, 3.6-9.5% and 6.6-11.7%, respectively. Free insulin decreased in plasma (p less than 0.05) and serum (p less than 0.01) at room temperature after 3 h and in promptly analyzed serum (p less than 0.01). Storage of samples at -20 degrees C increased the concentration of free insulin in plasma (p less than 0.025) and serum (p less than 0.005), whereas the free insulin content of supernates after PEG precipitation was stable, except for a slight decrease in serum samples (p less than 0.02). We conclude that, for radioimmunoassay of free and total insulin, plasma should be used, treated with PEG without delay; supernates then are analytically stable for as long as 26 weeks at -20 degrees C.
Antibodies↗
[Insulin treatment of type I diabetes--a review].
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Diabetes Mellitus, Type 1↗
Free insulin profiles in insulin-dependent diabetics treated with one or two insulin injections per day.
Twenty-four hour profiles of free insulin and blood glucose were determined in 12 healthy controls and 10 insulin-dependent diabetics treated with insulin regimens based on intermediate-acting insulin injected subcutaneously once or twice a day. The diabetics were ambulatory and in a good glycemic control, i.e. without hyperglycemic symptoms or frequent hypoglycemias and with HbA1 less than 9% (reference value 5.9-7.8%). Body weight was normal and median age (32 years) was the same in both groups. Free insulin was determined after polyethylene glycol precipitation of antibody-bound insulin. The controls had a low basal insulin level (median fasting value 3.9 mU/l) and postprandial peaks with a maximum within 30-60 min. There was no rise in plasma free insulin or blood glucose in the early morning hours. The free insulin profiles in the diabetics were highly unphysiological with hyperinsulinemia between the meals and during the night. The highest plasma free insulin value during the 24 hours was reached before lunch (approximately 5-fold compared to normals, p less than 0.01). Postprandially the free insulin concentrations did not reach the peak levels of the normals. After breakfast, blood glucose rose considerably in the diabetics (p less than 0.02 compared to normals) while the rise after lunch and dinner was not higher than in the healthy controls. The difficulties in glycemic control in the diabetic group, i.e. a blood glucose rise after breakfast and hypoglycemias in some patients, could largely be explained by the unphysiological insulin profiles.
Adult↗
Effect of fasting and refeeding on glucose metabolism in rat aorta.
The effect of refeeding on accumulation of [14C]glucose carbon, oxidation of [14C]glucose and glycogen concentration in rat aortic intima-media was studied in rats fasted for 3 days. Accumulation of glucose carbon and glucose oxidation were determined by incubating rat aorta in vitro for 2 h with 5.6 mM 14C-labelled glucose in the medium. Refeeding with standard pellets for 2-4 h augmented [14C]glucose accumulation in rat aorta but had no significant effect on glucose oxidation. The glycogen concentration in rat aorta tended to increase. After refeeding for 16 h both [14C]glucose incorporation and [14C]glucose oxidation were increased in rat aorta. Refeeding with carbohydrate-rich pellets (92% carbohydrate) for 3 h increased blood glucose more than did protein-rich (92% protein) pellets, whereas the rise in plasma insulin was about the same. The accumulation of [14C]glucose carbon measured during the subsequent in vitro incubation for 2 h was augmented after refeeding with protein-rich pellets and slightly reduced after carbohydrate-rich pellets. Refeeding of diabetic rats for 2 h with standard pellets increased plasma insulin and markedly increased blood glucose but had no effect on aortic [14C]glucose incorporation. Intravenous infusion of glucose in normal rats for 2 h markedly raised blood glucose but did not increase the aortic glucose incorporation. Raising the ambient glucose concentration from 5 to 10 mM during incubation of normal rat aorta in vitro for 2 h slightly decreased the [14C]glucose incorporation determined during a subsequent incubation for 2 h. These results suggest that refeeding with standard pellets augments glucose incorporation and glucose oxidation in rat aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Epidemiology of diabetes mellitus in Sweden. Results of the first year of a prospective study in the population age group 15-34 years.
All newly diagnosed cases of diabetes mellitus aged 15-34 years in Sweden, where the population in this age interval is about 2.3 million, were registered on standardized forms. During 1983, the first year of the study, there were 311 males and 161 females, excluding 280 with gestational diabetes. The annual incidence of diabetes was 26.2 per 100,000 in males and 14.2 in females. The respective figures for type I were 18.5 and 10.1, and for type II 5.7 and 2.9. The incidence of type I diabetes was similar for the four age groups (15-19, 20-24, 25-29, 30-34 years), while for type II it was highest in the oldest group. Types I and II, but not the sexes, differed as regards the cumulative distribution curves of the maximum blood glucose concentration during the first two weeks after diagnosis. The present incidence of diabetes in Sweden is higher, particularly in males than the rates for similar age groups in Oslo (1925-64) and Denmark (1970-77).
Adolescent↗
Abnormal concentration of stable HbA1 in non-diabetic patients.
To study its specificity for hyperglycemia, stable HbA1 was determined with ion-exchange chromatography in 240 patients consecutively hospitalized in the department of internal medicine and in a non-diabetic reference population. Reference values were found to increase significantly with age in the age groups less than 30, 30-60, and greater than 60 years. 41 patients had stable HbA1 more than 2 SD above the mean of the reference group and random blood glucose less than 7 mmol/l, and 21 of these were classified as non-diabetics according to data in medical records. Four non-diabetic patients had stable HbA1 higher than + 4 SD. One of them had haemoglobinopathia, one severe anaemia under cortisone treatment, one cortisone treated myelomatosis with renal insufficiency and severe anaemia, and one patient had lymphoma and renal insufficiency. Nine patients had stable HbA1 between + 3 and 4 SD and diagnoses of coronary heart disease (4), rheumatoid arthritis (2), asthma (1), chronic renal failure (1) and malignant melanoma (1). Five of them were treated with cortisone or diuretics. Four patients had stable HbA1 slightly below the reference range. In summary marked elevation of stable HbA1 due to factors other than diabetes occurred in a few patients with haematological disorders.
Adult↗
Effect of insulin treatment on the blood-retinal barrier in rats with streptozocin-induced diabetes.
Eighteen rats were made diabetic with a single intravenous dose of streptozocin; 16 rats served as nondiabetic controls. Fluorescein sodium was injected into the tail vein for fluorophotometry. After insulin therapy, metabolic control was improved in the diabetic animals, but normoglycemia was not achieved. The vitreous fluorescein level in diabetic animals was significantly higher than in controls before insulin treatment, but it decreased after six to seven days of insulin therapy. There was no significant alteration of the fluorescein concentration in the vitreous body of the controls when vitreous fluorophotometry was repeated after six to seven days. The plasma fluorescein concentration was lower in the diabetic than in the nondiabetic animals and unaltered after insulin treatment. The results imply that the dysfunction of the blood-retinal barrier in the diabetic rats is reversible by insulin therapy. It is probably related to the diabetic state and not to a toxic effect of streptozocin.
Animals↗
Characteristics of labile HbA1 in erythrocytes from normals and diabetics.
Incubation of erythrocytes from diabetic patients and non-diabetic persons in 0.15 mol/l saline at 37 degrees C was followed by a decrease in ion-exchange microcolumn determined HbA1 only during the first 4 h. The fraction removed was denoted as labile HbA1 and the remaining fraction as stable HbA1. Incubation in saline overnight at 20 degrees C did not completely remove the labile fraction. Incubation in saline overnight at 4 degrees C yielded only a slight decrease in labile HbA1. Incubation in saline containing various glucose concentrations (up to 100 mmol/l) produced increasing amounts of HbA1 during the first 3-4 h after which an equilibrium was reached. In both normal and diabetic erythrocytes incubated for 3-4 h we found a linear relationship between changes in labile HbA1 and glucose concentration. The degree of increase in labile HbA1 was the same in normals and diabetics and not dependent on pre-existing normal or moderately increased stable HbA1. In the blood from non-diabetics (n = 30) labile HbA1 was 0.5 +/- 0.3% (mean +/- SD) and in diabetics (n = 80) 1.6 +/- 0.8%. The correlation between labile HbA1 and simultaneously determined blood glucose was r = 0.72.
Blood Glucose↗
Influence of anoxia and dinitrophenol on the phosphorylase a activity and the cyclic nucleotide content of smooth muscle.
The effect of anoxia or 2,4-dinitrophenol (DNP) on the phosphorylase activity and the cyclic AMP and the cyclic GMP content was studied in smooth muscle preparations. When the aerobic conditions were changed to anaerobic in experiments on bovine mesenteric artery, there was a significant increase in the activity of phosphorylase a during the first 60 min. We had observed a reduction of the glycogen content of the artery during this time period, which accounted for about 2/3 of the increase in lactate production (Pasteur effect). Under anaerobic conditions the content of cyclic AMP in the vessel was not changed, and the increase in phosphorylase a activity was not inhibited by a blockade of adrenergic beta-receptors. DNP, which like anoxia inhibits the mitochondrial production of ATP, increased the phosphorylase a activity to the same extent as anoxia. Anoxia and DNP also enhanced the activity of phosphorylase a in pig thoracic aorta and rabbit colon smooth muscle. In thoracic aorta both anoxia and DNP produced a more transient and smaller increase in the phosphorylase a activity than in the mesenteric artery. The Pasteur effect was also relatively smaller (100%) in thoracic aorta than in mesenteric artery (400%). It is suggested that an anoxic increase in the phosphorylase a activity participates in the Pasteur effect in smooth muscle.
2,4-Dinitrophenol↗
Rapid and slow rate of decrease in HbA1a + b and HbA1c during improved glycaemic control.
The change in glycosylated haemoglobins was studied with a column chromatographic method when glycaemic control was rapidly improved in nine diabetic patients. The patients were followed for 3 weeks or more. There was a decrease in HbA1a+b and HbA1c within the first few days of improved control and this decrease was faster than later on. The initial decrease of HbA1a+b was faster than that of HbA1c. In individual patients the initial decrease in glycosylated haemoglobins correlated with the initial rate of decrease in blood glucose. It is concluded that HbA1a+b and HbA1c decrease biphasically during improved glycaemic control. The rapid initial decrease may be due to labile HbA1 and it is large enough to influence the value of HbA1 as an indicator of long-term glycaemic control in some patients.
Adolescent↗