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Biomedical subjects

H Orskov

Publications and source records attributed to H Orskov.

285 records · Page 16Linked to original sources
PubMed1968

The relationship between endogenous serum insulin concentration and glucose uptake in the forearm muscles of nondiabetics.

IN A SERIES OF EXPERIMENTS ON THE HUMAN FOREARM, PREPARATION DESIGNED TO EXAMINE THE EFFECTS OF VARIATIONS IN IMMUNOLOGICALLY DETERMINED ENDOGENOUS SERUM INSULIN LEVELS AND OF BLOOD GLUCOSE CONCENTRATIONS ON MUSCULAR GLUCOSE UPTAKE, THE FOLLOWING RESULTS WERE OBTAINED: (a) A highly significant correlation between muscular glucose uptake and simultaneous arterial serum insulin concentration. (b) No correlation between glucose uptake and simultaneous arterial blood glucose concentration during hyperglycemia. (c) A maximal insulin effect on muscular glucose uptake at arterial serum insulin concentrations at about 200 muU/ml. This observation is, however, based on only a few experiments.

Adult↗
PubMedDate not supplied

Circulating levels of free insulin-like growth factors in obese subjects: the impact of type 2 diabetes.

BACKGROUND: Obese subjects show major abnormalities in the growth hormone (GH)/insulin-like growth factor (IGF) system. Furthermore, they are prone to develop Type 2 diabetes, but the impact of diabetes plus obesity on the GH/IGF system remains unknown. METHODS: We compared overnight fasting serum levels of free and total (extractable) IGF-I and -II, IGF-binding protein (IGFBP) -1, -2 and -3, and the high affinity GH-binding protein (GHBP) in matched groups of lean subjects (n=26) and obese subjects without (n=24) and with (n=29) Type 2 diabetes. Two groups (n=7) of healthy and Type 1 diabetic subjects were also studied. RESULTS: Non-diabetic obese subjects had increased free IGF-I and -II, total IGF-II, IGFBP-3 and GHBP, reduced IGFBP-1 and -2 (p<0.05), but normal total IGF-I, when compared to lean subjects. In obese Type 2 diabetics free IGF-I was insignificantly reduced by 9% (p=0.3), when compared to non-diabetic obese subjects. However, the concentration was not significantly elevated when compared to that of lean controls (p=0.13). Also IGFBP-1 and total IGF-I were normal in obese Type 2 diabetics, whereas free and total IGF-II and IGFBP-3 remained elevated to a similar extent as in simple obesity (p<0.05). In contrast, GHBP was further increased and IGFBP-2 further reduced in obese Type 2 diabetics (p<0.05). In Type 1 diabetics total IGF-I and -II, and IGFBP-3 were normal. In contrast, free IGF-I and -II and GHBP were markedly reduced, whereas IGFBP-1 and -2 were increased (p<0.05). CONCLUSIONS: Simple obesity was associated with marked changes in the GH/IGF system. Many of these abnormalities were unaffected by the concomitant presence of Type 2 diabetes (total IGF-I, free and total IGF-II and IGFBP-3). However, some changes became accentuated (GHBP and IGFBP-2), while others (free IGF-I and IGFBP-1) were no longer present. Notably, the impact of Type 1 diabetes on the GH/IGF system was clearly different from that of Type 2 diabetes.

Analysis of Variance↗
PubMedDate not supplied

Suppression of the night increase in serum TSH during development of ketosis in diabetic patients.

The alterations in metabolic parameters, circulating iodothyronines and serum TSH were studied during a 21 h period of insulin withdrawal in 6 young patients with juvenile type diabetes mellitus. Concomitant with the derangement of metabolic state a significant fall in serum T3 (in average 27%), serum free T3 (28%), and T4 (12%) was observed. SErum free T4 remained unchanged. Before and after the period of ketosis the normal diurnal pattern of high serum TSH at night and low levels during the daytime period was observed. During the period of ketosis the night level of serum TSH was significantly depressed (46 +/- 9% lower at 23.00 h, p less than 0.01) while no significant alterations occurred in daytime TSH. Both the variations in T3, reverse T3 (rT3) and night TSH were correlated to the increase in blood-3-hydroxybutyrate. The depression of the night surge in serum TSH may be of importance for the fall in circulating levels of active iodothyronines during the initial phase of illness, together with the well known inhibition of T4 deiodination to T3 in peripheral tissues occurring in acute illness.

3-Hydroxybutyric Acid↗
PubMedDate not supplied

The metabolic effects of quinine in children with severe and complicated Plasmodium falciparum malaria in Dar es Salaam.

Quinine is widely used for the treatment of severe and complicated malaria, although resistant strains of Plasmodium falciparum may occur. The drug has been incriminated as a cause of hypoglycaemia in some malaria patients. To determine if quinine has untoward metabolic effects during treatment of severe and complicated malaria we have studied the effects of quinine on blood glucose and intermediary metabolites, serum insulin, C-peptide, plasma glucagon and non-esterified fatty acids in 97 children with severe malaria in Dar es Salaam. All patients responded clinically. No patient developed hypoglycaemia while on quinine therapy given as 10 mg/kg in 10 ml/kg of 5% dextrose infused over 4 h every 8 h. Endogenous insulin secretion, as reflected by C-peptide levels, increased after 4 h but insulin levels did not change significantly. Blood lactate, 3-hydroxybutyrate, plasma non-esterified fatty acids and plasma glucagon all fell appropriately during treatment. We conclude that quinine, when administered at the recommended dose and rate, does not disrupt blood glucose homeostasis, and is still the drug of choice for severe and complicated malaria in children.

Blood Glucose↗
PubMedDate not supplied

Diabetes-like alterations in hemostatic parameters after growth hormone administration for one week in normal man.

Excess production of growth hormone (GH) in poorly controlled diabetes is believed to be a causal factor in the development of diabetic angiopathy, the mechanism(s) of which is unknown. The present study was undertaken to determine whether exogenous growth hormone would specifically change some quantities and functional parameters known to often be abnormal in long-standing diabetes and thought to result from the development of vascular lesions in general. The authors studied capillary resistance, factor VIII coagulant antigen (F VIII:Ag), von Willebrand factor (vWf:Ag), fibronectin, fibrinogen, and tissue-type plasminogen activator (t-PA) before, during, and after 1 week's subcutaneous GH administration (6 IU per day divided into two doses). Capillary resistance decreased insignificantly, but returned to higher levels (p less than 0.05) 1 week after withdrawal. F VIII:Ag, vWf:Ag, fibronectin, and fibrinogen all increased significantly during GH treatment. Except for F VIII:Ag, these quantities returned to pre-medication levels 7 days after termination of GH administration. The present results may contribute to the clarification of the role of GH hypersecretion in diabetic microangiopathy and macroangiopathy.

Adult↗
PubMedDate not supplied

Metabolic control in newly kidney transplanted insulin-dependent diabetics: improvement by insulin pump treatment (CSII).

Management of glucose homeostasis in newly kidney transplanted insulin-dependent diabetic patients is difficult. To examine whether continuous subcutaneous insulin infusion (CSII) could reverse this problem, six consecutive kidney-transplanted Type I diabetic patients either proceeded with conventional insulin therapy (CIT) or were changed to CSII beginning on the third postoperative day. After a mean of 13 days, the insulin administration mode was changed from CIT to CSII (n = 3) or from CSII to CIT (n = 3), and continued for a further 15 days. Mean blood glucose calculated on the basis of four daily measurements (8.00, 12.00, 17.00, 22.00 h) during the study periods was significantly lower during CSII (8.0 +/- 0.4 mmol/l, mean +/- SEM) than on CIT (11.0 +/- 0.6 mmol/l; p less than 0.005). Moreover, the variability of blood glucose expressed as the M-value was lower during the pump treatment compared to CIT (p less than 0.001), while the number of blood glucose values below 3.0 mmol/l was similar (3.8 vs. 4.4%). Diurnal metabolic and hormonal profiles were twice determined on each regimen with 2 hourly sampling. Glycemic control was again found to be improved during CSII therapy as compared to CIT (p less than 0.01 or 0.05 less than p less than 0.10). Moreover, insulin pump treatment resulted in a significant reduction of two major intermediary metabolites, lactate and glycerol (p less than 0.05 and p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMedDate not supplied

The calcium channel blocker nitrendipine attenuates renal and glomerular hypertrophy in diabetic rats.

The efficacy of the calcium channel blocker nitrendipine in preventing early renal and glomerular hypertrophy and increased urinary albumin excretion (UAE) was studied in experimental diabetes in rats, starting treatment at the onset of diabetes. Female Wistar rats were randomised into four groups: diabetic and non-diabetic rats were given either placebo or nitrendipine (250 mg/kg) in the diet for 8 weeks. After 8 weeks the kidneys in the diabetic animals had increased significantly compared to the non-diabetic controls. In the diabetic nitrendipine-treated animals renal and glomerular hypertrophy was significantly smaller than in the diabetic placebo-treated group (p < 0.05). After an initial increment within the first week, the UAE remained constant throughout the study period in the diabetic nitrendipine-treated animals, while a steady increase was seen in the diabetic placebo-treated group (p < 0.05). No differences were seen in systemic blood pressure between calcium- channel-blocker-treated groups and placebo-treated groups. In conclusion, administration of nitrendipine to diabetic rats for 8 weeks had a significant inhibitory effect on renal and glomerular hypertrophy, and showed a tendency towards a reduction in UAE (p = 0. 06) without affecting metabolic control or systemic blood pressure.

Albuminuria↗
PubMedDate not supplied

Glucose metabolism in chronic renal failure with reference to GH treatment of uremic children.

Growth retardation is a common feature in children with end-stage renal failure (ESRF). Medical management of renal insufficiency rarely normalizes growth and optimistic reports on the effect of rhGH treatment on growth velocity may presage more extensive use of rhGH in pediatric nephrology. Ample evidence has shown beneficial effects of GH replacement therapy in both childhood and adolescent hypopituitarism. However, the remarkably few side effects of treatment reported in these conditions cannot necessarily be extrapolated to children with ESRF. Uremia is associated with a wide range of metabolic and hormonal derangements including decreased glucose tolerance. This is mainly due to impaired insulin-stimulated glucose disposal in peripheral tissues and insufficient insulin-induced suppression of hepatic glucose production. Insulin-stimulated glucose uptake in skeletal muscle in ESRF is reduced by 30-50% as compared to that in healthy subjects, and a reduction may be detected even in subjects with a more moderate reduction in renal function (GFR around 25 ml/min). Dialysis therapy improves the disturbed insulin action significantly. The cause of the insulin resistance in ESRF is multifactorial. Impaired physical fitness, accumulation of uremic toxins, raised levels of GH and glucagon, metabolic acidosis, dyslipidemia and the medication applied may all contribute. If exogenous GH administration is added to the already marked uremic insulin resistance, insulin action may be severely disturbed and the secondary hyperinsulinism further magnified. However, frank diabetes mellitus does not develop unless the beta cells fail to meet the enhanced demands. This will probably occur only in patients with a beta-cell genotype pivotal for the phenotypic expression of non-insulin dependent diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMedDate not supplied

Insulin action in insulin-dependent diabetics after short-term thiazide therapy.

The influence of short-term thiazide treatment on peripheral tissue and liver sensitivity to insulin in insulin-dependent diabetes mellitus was determined by the euglycemic insulin clamp technique. A sequential three-step hyperinsulinemic clamp was performed in six insulin-dependent diabetics before and after 2 wk of hydroflumethiazide (HFT) administration in a daily dose of 75 mg. Insulin was infused at rates of 0.5, 2.0, and 4.0 mU X kg-1 X min-1, and each dose was given for at least 120 min. Glucose uptake during the last 30 min of each step was almost identical in the two situations (2.7 +/- 0.6 vs. 2.4 +/- 0.5 mg X kg-1 X min-1, 9.6 +/- 0.9 vs. 9.7 +/- 1.2 mg X kg-1 X min-1, and 12.0 +/- 1.3 vs. 12.6 +/- 1.5 mg X kg-1 X min-1). Serum insulin levels were also similar, and blood glucose was kept at 100 +/- 3, 99 +/- 4, and 97 +/- 3 mg/dl before thiazides and at 93 +/- 6, 93 +/- 6, and 94 +/- 6 mg/dl after thiazides. Another five insulin-dependent diabetics were infused with tritiated glucose followed by insulin infusion at two rates: 0.45 and 1.0 mU X kg-1 X min-1. Basal glucose output was comparable before and after thiazides (3.63 +/- 0.24 vs. 2.97 +/- 0.26 mg X kg-1 X min-1), as was the liver response to increasing insulin concentrations. The metabolic state as assessed by HbA1c and fasting blood glucose did not differ in the two experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Effect of lanreotide on local kidney IGF-I and renal growth in experimental diabetes in the rat.

Initial diabetic renal hypertrophy is preceded by a transient increase in kidney insulin-like growth factor I(IGF-I). In the present study streptozotocin-diabetic rats were treated with a new somatostatin analogue (lanreotide), insulin or placebo for 7 days and compared to non-diabetic control rats. Kidney IGF-I changes were examined in the renal cortex, medulla, and whole kidney homogenates. The renal cortex contained approximately 5.5 times more IGF-I than the renal medulla (p < 0.01); further, IGF-I increased transiently and more pronouncedly in the renal cortex compared to the medulla. Lanreotide treatment significantly inhibited diabetic renal and glomerular growth compared to placebo-treated diabetic rats. Further, lanreotide treatment was followed by a significantly lower medulla IGF-I by day 2, while lanreotide had no effect on cortex IGF-I accumulation. In conclusion, IGF-I accumulated transiently and was more pronounced in the real cortex compared to the renal medulla and, further, lanreotide prevented diabetic renal and glomerular growth bringing new evidence that intervention with somatostatin analogues may have a role in the prevention of experimental diabetic kidney disease.

Animals↗