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Biomedical subjects

K F Hanssen

Publications and source records attributed to K F Hanssen.

At least 91 records · Page 5Linked to original sources

Effect of near normoglycaemia for two years on progression of early diabetic retinopathy, nephropathy, and neuropathy: the Oslo study.

Forty five insulin dependent diabetics were randomised to treatment with continuous subcutaneous insulin infusion (CSII), multiple insulin injections (five or six daily), or conventional twice daily insulin injections. Near normoglycaemia was obtained with CSII and multiple injections but not with conventional treatment (p less than 0.01). Hypoglycaemic coma was observed less frequently with CSII than with multiple injections and conventional treatment (p less than 0.001), but blood glucose concentrations below 2.5 mmol/l (45 mg/100 ml) were more common. After two years fewer retinal microaneurysms and haemorrhages had developed in the patients given CSII and multiple injections compared with those given conventional treatment, in whom the number had increased significantly (p less than 0.01). Motor nerve conduction velocity deteriorated in the patients given conventional treatment; in those given CSII it was unchanged during the first year but had improved after two years (p less than 0.01). Glomerular hyperfiltration was reduced with CSII, but no change occurred in urine albumin excretion rates. Long term near normoglycaemia may prevent the progression of early stages of late diabetic complications.

Blood Glucose↗

Diabetic control is improved by guar gum and wheat bran supplementation.

Twenty-eight insulin-dependent diabetics were treated with different dietary regimes for three periods of three months. Initially they used a white flour bread (run-in period), then their daily bread ration was enriched with guar gum (mean dose: 29 g), and then with wheat bran (mean dose: 33 g) in a randomized crossover pattern. Fasting and postprandial blood glucose levels were measured on filter paper spots collected once weekly at home, and other biochemical values were measured monthly. No improvement in diabetic control was seen during the run-in period. Mean postprandial blood glucose decreased from 12.0 +/- 3.8 mmol/l (mean +/- SD) in the run-in period to 9.7 +/- 2.8 mmol/l (p less than 0.01) in the guar period and to 9.7 +/- mmol/l (p less than 0.01) in the bran period. HbA1 decreased from 10.5 +/- 2.1% in the run-in period to 9.7 +/- 1.6% (less than 0.05) at the end of the guar period and 9.9 +/- 1.2% (not significant) at the end of the bran period. Only modest changes were seen in serum-lipids--total cholesterol decreased significantly in the guar period, but not in the bran period. In this study both guar gum and wheat bran were well tolerated and produced a substantial decrease in postprandial blood glucose.

Adolescent↗

Somatostatin, insulin and glucagon after arginine stimulation in active and treated acromegaly.

Ten acromegalic patients, 28-71 years old, were compared with 10 normal controls, 21-39 years old. In another study, 7 patients with active acromegaly, 19-70 years old, were investigated before and 4-9 months following transsphenoidal adenectomy and radiation. They were all investigated following an arginine infusion (0.5 g/kg/20 min). Although the mean plasma somatostatin (somatotrophin release inhibiting factor (SRIF] was somewhat higher in acromegalic patients compared to normal controls (mean basal values 21 +/- 3.8 and 16.6 +/- 2.1 pmol/l, respectively), the difference was not significant. The patients had higher serum insulin (peak values 118 +/- 23.9 and 63 +/- 11.8 mU/l, respectively) and lower plasma glucagon (peak values 171 +/- 29.0 and 310 +/- 52.7 pmol/l, respectively). Plasma SRIF increased during arginine infusion, but the concentrations were similar before and following the operation (mean basal values 18.2 +/- 2.6 and 15.2 +/- 2.3 pmol/l, respectively). Serum insulin was significantly higher before the operation (peak values 154 +/- 38.8 and 91 +/- 24.9 mU/l, respectively). Plasma glucagon was similar before and after the operation (peak values 143 +/- 23.4 and 127 +/- 22.7 pmol/l, respectively). Plasma SRIF is similar in active acromegaly and normal controls, and in acromegaly before and following treatment, despite differences in serum growth hormone (GH), serum insulin and plasma glucagon. This points towards a modulating role for GH on plasma SRIF, possibly by affecting the other islet cell hormones.

Acromegaly↗

Plasma somatostatin is elevated in primary hypothyroidism compared with hyperthyroidism.

Increased pancreatic somatostatin (somatotrophin release inhibiting factor (SRIF) has been found in hypothyroid rats. Therefore, we wanted to investigate plasma SRIF in patients with hypo- and hyperthyroidism. Two groups of patients, 7 cases with autoimmune hypothyroidism, 31-75 years old, and 7 cases with Graves' disease, 19-43 years old, were compared with regard to plasma SRIF before, during and after an arginine infusion (0.5 g/kg/20 min). None of the patients suffered from diabetes mellitus or obesity. Plasma SRIF was higher in the hypothyroid patients (mean basal value 21.5 +/- 3.9, peak value 28.7 +/- 5.1 pmol/l) compared with the hyperthyroid group (mean basal value 11.6 +/- 3.3, peak value 16.2 +/- 4.0 pmol/l). The hypothyroid group also had significantly higher serum insulin values during arginine stimulation. No difference was found in plasma glucagon, serum growth hormone (GH) or blood glucose. In conclusion, plasma SRIF is elevated in primary hypothyroidism compared with hyperthyroidism. The reason for this finding is uncertain, but a reduced SRIF clearance is a possible explanation. The association of our findings with the reduced glucose tolerance in hyperthyroidism is discussed.

Adult↗

Plasma somatostatin and plasma glucagon in long-term IDDM without residual B-cell function. No effect of different long-term metabolic control.

To further study the elevated plasma somatostatin (SRIF)--and reduced plasma glucagon concentrations found in IDDM patients without residual B-cell function compared to normal controls, we investigated 39 such patients, randomly assigned to three different insulin treatment regimens; conventional therapy with two injections a day (CTh), insulin pump (CSII) and multiple injections (MI), for 1 year. They were given an arginine infusion (0.5 g/kg/20 min). The mean basal plasma SRIF values in the CTh, CSII and MI groups were 20.8 +/- 3.3, 18.6 +/- 1.8 and 20.6 +/- 2.8 pmol/l and the mean basal plasma glucagon values were 30 +/- 5.7, 19 +/- 2.3 and 27 +/- 4.7 pmol/l, respectively. Both SRIF and glucagon increased in all groups in relation to arginine infusion. For both hormones, the mean values were highest in the CTh group, lowest in the CSII group, although the differences were not significant. The mean HbA1 values for the last 3 months within the test were 10.0 +/- 0.5, 8.8 +/- 0.3 and 9.1 +/- 0.5%, respectively, in the same order as above. The CTh group had significantly higher HbA1 values than the CSII group (p less than 0.02). We conclude that small differences in long-term blood glucose control are of inconsiderable importance for the islet hormonal response to arginine found in IDDM without B-cell function.

Adult↗

Effects of intensified insulin treatment on various lesions of diabetic retinopathy.

Mild background retinopathy was studied prospectively during long-term strict blood glucose control in insulin-dependent diabetes mellitus. Forty-five subjects (21 women and 24 men with a mean age of 26.3 years and a mean duration of diabetes of 12.8 years) were randomly assigned to continuous subcutaneous insulin infusion, multiple injections, and conventional two-injection treatment. Eyes were examined two months before treatment, at the beginning of treatment, and after three, six, and 12 months. A progressive deterioration was found in the two-injection group during the study, but no significant changes were found in patients receiving multiple injections. A transient deterioration occurred after three months of continuous subcutaneous insulin infusion. Soft exudates appeared in 50% of the patients on the two intensified regimens, but no exudates were found in patients given conventional treatment. The morphologic changes seemed to be related to a large and rapid decrease in mean blood glucose or to an increased frequency of hypoglycemia, or both.

Adolescent↗

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.

Adolescent↗

Effects of synthetic corticotropin-releasing factor in normal individuals and in patients with hypothalamic-pituitary-adrenocortical disorders.

Plasma adrenocortical hormone (ACTH) and cortisol response to four dose levels (25, 50, 100 and 300 micrograms) corticotropin-releasing factor (CRF) were studied in 5 healthy men, and the response to 100 micrograms CRF in 12 patients with various disorders of the hypothalamic-pituitary-adrenocortical function. In normals, mean plasma ACTH and cortisol concentration rose at all dose levels of CRF and peaked at 30 and 60 min respectively. The increment in plasma cortisol at 60 and 90 min was significantly higher on 100 and 300 micrograms CRF than on 25 micrograms, but the total cortisol concentration was not. Seven patients had Cushing's syndrome. In 2 patients with adrenocortical carcinoma the basal plasma ACTH was suppressed. After CRF a small increase was seen in plasma ACTH and cortisol in one patient successfully treated with mitotane, while the other patient did not respond. In 1 patient with ectopic ACTH syndrome an increase in plasma ACTH 15 min after CRF was not accompanied by any increase in plasma cortisol. One patient with bilateral multinodular adrenocortical hyperplasia did not respond to CRF. The plasma ACTH and cortisol response to CRF was supernormal in 2 patients with Cushing's disease, while a third patient responded in the normal range. In 2 patients with Nelson's syndrome the plasma ACTH response was excessive. Two out of three hypophysectomized patients did not respond to CRF, while one patient with a slightly positive response to hypoglycemia also responded (subnormally) to CRF. Our data indicate that CRF in doses of 50-100 micrograms will be a valuable substance in the differential diagnosis of Cushing's syndrome. Some overlap in the response is, however, seen between patients with Cushing's disease and other patients with Cushing' syndrome. CRF will possibly be of value also for the diagnosis of secondary adrenocortical failure.

Adrenocorticotropic Hormone↗

Increased peripheral venous somatostatin concentration and decreased glucagon response to arginine in patients with insulin dependent diabetes mellitus without residual B-cell function. Increased plasma SRIF in IDDM.

The glucagon response to insulin hypoglycaemia is frequently reduced in patients with IDDM. In the present study arginine infusion, thought to act directly on the islet cells, was used to stimulate somatostatin (SRIF) and glucagon in IDDM without residual B-cell function. Thirteen IDDM patients' were compared with 13 sex- and age matched normal controls following an arginine infusion. The plasma SRIF concentrations in the 'IDDM group' and normal controls increased from 24.2 +/- 2.5 to 31.1 +/- 3.9 pmol/l (P less than 0.01) and 19.7 +/- 1.7 to 23.9 +/- 3.4 pmol/l respectively after 10 min (P less than 0.01). The plasma glucagon concentrations increased from 27 +/- 4.7 to 176 +/- 23.1 pmol/l (P less than 0.01) and 36 +/- 5.0 to 302 +/- 31.9 pmol/l (P less than 0.01) respectively after 20 min. Thus, in long standing IDDM without residual B-cell function, increased plasma SRIF concentrations are found and the glucagon response to arginine is reduced. The last observation further explains why these patients are especially vulnerable to hypoglycaemia.

Adolescent↗

The influence of strict control on diabetic complications.

We studied 45 IDDM without c-peptide response, duration 7-22 years, without proliferative retinopathy. After 2 months run-in period, they were randomly assigned to: (P) 15 received CSII: (C) 15 received multiple s.c. injections via butterfly 5-6x daily;: (M) 15 received twice daily mixed rapid and long acting insulin. All groups improved blood glucose control in the run-in period (p less than 0.0001). After change of treatment (P) and (M) improved further (p less than 0.01) but (C) was unchanged. GFR was supranormal and decreased in (P) and (M). No regression of retinopathy was shown in any group. One in (P) had transient florid pre-proliferative retinopathy which regressed spontaneously without laser treatment. We conclude that retinal response to strict control is complex. A transient deterioration may been seen.

Adolescent↗

Arginine infusion increases peripheral plasma somatostatin in man.

A somatostatin (SRIF) radioimmunoassay is described, using an antiserum raised in rabbit, reacting more with SRIF-14 than -28. Glass tubes were employed for the assay because our tracer, 125I 1-Tyr-SRIF, was adsorbed to plastic (23% non specific binding). Vycor extraction was used, and following Sephadex G-50 chromatography, the plasma extract showed two forms, coeluting with SRIF-28 and -14. Fifteen healthy subjects, eight women and seven men, 21-39 years old, received an infusion of arginine chloride (2.38 mmol/kg) for 20 min, or saline. An immediate rise in plasma SRIF from the mean basal level at 2 min was shown. Maximal value was 24.0 +/- 3.0 pmol/l (P less than 0.01) after 10 min followed by a rapid descent towards the basal level after the infusion. A temporal relationship was observed between the SRIF, insulin and glucagon responses following arginine infusion, while the GH levels increased only after the SRIF levels had declined, indicating an inhibition of GH. This is further supported by the high degree of correlation (r = 0.87) between SRIF- and GH increments. It is suggested that plasma SRIF measurement during arginine infusion gives an estimate of the pancreatic SRIF releasing capacity.

Adult↗

Biosynthesis and release of thyrotropin-releasing hormone immunoreactivity in rat pancreatic islets in organ culture. Effects of age, glucose, and streptozotocin.

Thyrotropin-releasing hormone immunoreactivity (TRH-IR) was measured in isolated islets and in medium from rat pancreatic islets maintained in organ culture. TRH-IR in methanol extracts of both islets and culture medium was eluted in the same position as synthetic TRH by ion-exchange and gel chromatography and exhibited dilution curves parallel with synthetic TRH in radioimmunoassay. [3H]Histidine was incorporated into a component that reacted with TRH antiserum and had the same retention time as synthetic TRH on reversed-phase high-performance liquid chromatography. A continuous release of TRH-IR into the culture medium was observed from islets of both 5-d-old (newborn) and 30-d-old (adult) rats with a maximum on the second day of culture (28.7 +/- 7.0 and 13.3 +/- 3.6 fmol/islet per d, respectively). The content of TRH-IR was higher in freshly isolated islets from newborn rats (22.4 +/- 2.3 fmol/islet) than in adult rat islets, which, however, increased their content from 1.3 +/- 0.5 to 7.0 +/- 0.5 fmol/islet during the first 3 d of culture. Adult rat islets maintained in medium with 20 mM glucose released significantly more TRH-IR than islets in 3.3 mM glucose medium (13.0 +/- 0.7 vs. 4.3 +/- 0.3 fmol/islet per d). In contrast, the content of TRH-IR in the islets was reversed (1.4 +/- 0.3 vs. 4.7 +/- 1.6 fmol/islet). By exposing islets from newborn rats to streptozotocin 0.7 mg/ml for 30 min, a 50% reduction of TRH-IR content in the islets compared with the non-treated islets was seen after subsequent culture for 7 d. The insulin content was reduced by 80%, while glucagon was slightly elevated. In conclusion, these results indicate that TRH is synthesized in rat pancreatic islets, and that the release is stimulated by glucose.

Aging↗

Thyrotropin-releasing hormone immunoreactivity in the gastrointestinal tract of man.

TRH inhibits gastric secretion, gastric motility, and pancreatic enzyme secretion in man. We measured TRH immunoreactivity (TRH-IR) in mucosal and transmural biopsies from different parts of the stomach, pylorus, duodenum, and pancreas in patients undergoing surgery or gastroscopy. TRH-IR was found in pancreas (range, 1.64-3.27 pg TRH/mg protein) and in mucosa of the fundus (13.3 +/- 2.0 pg TRH/mg protein), antrum (22.5 +/- 4.5 pg TRH/mg protein), and duodenum (35.5 +/- 6.4 mg TRH/mg protein). Low levels of TRH-IR were found in transmural biopsies from fundus, antrum, and pylorus (range, 0.45-0.87 pg TRH/mg protein). Chromatography of gastrointestinal tissue extracts on a cation exchange column resulted in two different TRH-IR peaks, one eluted at pH 3.5 and the other eluted at pH 7.4. The peak at pH 7.4 corresponded to synthetic TRH. The presence and the action of TRH in human gut indicate a physiological role of TRH in the gastrointestinal tract in man.

Animals↗