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The concentrations of triiodothyronine (T3), thyroxine (T4) and thyroxine binding globulin (TBG) have been measured in serum of 20 patients with ulcerative colitis or Crohn's disease. The patient group was compared with 20 healthy control subjects matched for sex and age. The concentration of T3 and T4 were similar in the two groups but TBG in serum was higher in the patient group, mainly due to the high TBG levels in the female patients. The concentration of T3 in serum was lower in the severely ill patients than in those who were mildly-moderately ill, while T4 and TBG were not affected by the severity of the disease. The concentration of T3 was lower in the corticosteroid-treated patients than in those who did not have such treatment, just like the TBG level. However, TBG was not subnormal in the corticosteroid-treated patients, whereas the serum concentration of T3 was. T4 in serum was not affected by treatment with corticosteroids. These findings indicate that the metabolism of T4 and T3 are influenced differently by corticosteroids.

We have investigated the formation and reaction of phenyl fragments on Pd(1 1 1) and Pd(1 1 0), using synchrotron radiation-based photoelectron spectroscopy. The phenyl fragments are formed by carboniodine bond scission of iodobenzene, taking place already at 80 K. Pd(1 1 0) is seen to be more reactive than Pd(1 1 1) in this reaction. With annealing, the phenyl fragments subsequently form both benzene and biphenyl products. Ring coupling is found to be somewhat more efficient on Pd(1 1 1).

The adsorption of 2-butenal on the Pt(111), Pt(111)Sn-(2 x 2), and Pt(111)Sn-(root3 x root3)R30degrees surfaces has been studied by high-resolution photoelectron spectroscopy and DFT calculations. On Pt(111) 2-butenal adsorbs at a threefold hollow in a eta(3)(C,C,O) configuration. A similar geometry is observed for Pt(111)Sn-(2 x 2), although the oxygen coordinates to tin instead of platinum. As the surface coverage of tin increases, as for Pt(111)Sn-(root3 x root3)R30degrees, the most stable adsorption geometry changes to eta(1)(O), where the carbonyl oxygen once again coordinates to tin. The carbonyl bond thus retains an activated character as Pt/Sn alloys are formed. The alkene/surface interaction is, however, dramatically influenced at increasing surface concentrations of tin.

The influence of tin on the bonding of CO to Pt(l 10) has been studied using high-resolution electron energy loss spectroscopy, density functional theory and photoelectron spectroscopy. CO binds on-top to platinum at all investigated tin and CO coverages. Bonding of CO in Sn-Pt alloy rows is weakened compared to clean Pt(l 10). However, several different adsorption sites in Pt-only rows, inequivalent with regard to their coordination environment, show very similar characteristics with respect to CO adsorption.

Albumin concentrations persistently between 20 and 200 mg/L in first morning spot urine or urine collected overnight, referred to as microalbuminuria, indicate incipient nephropathy in diabetes mellitus. This study validates a new point-of-care device, the HemoCue Urine Albumin analyser, for handling, accuracy precision and predictive values (PV+/-) at 20 mg/L. Over a period of 2 months, 200 microalbuminuria samples were selected at the Department of Clinical Chemistry according to the results from the Integra 700 instrument (Roche, R) and analysed on the same day using the HemoCue analyser (HemoCue, H) and the Immage instrument (Beckman, B), in all cases closely following the manufacturers' instructions. Only 137 results were within the measuring range of H, 10-150 mg/L. Comparisons yielded regression lines H=1.06R-7.2 (r2=0.94), H=1.08B-3.1 (r2=0.94) and R=1.00B+4.3 (r2=0.99). Inter-assay (n=24) CV% at 12 mg/L was H=18.2, R=4.2 and B=2.9 and at 65 mg/L: H=6.1, R=1.8 and B=2.6. Intra-assay duplicate CV% for H at 21-40 mg/L was 13.2, at 41-80 mg/L 10.8 and at 81-150 mg/L 9.2. Intra-assay repeatability (n=8) CV% at 28 mg/L was 7.2-13.8, at 57 mg/L 6.4-8.4 and at 105 mg/L 4.3-7.1. External quality assurance urine albumin (B) was +5.7% cf. nephelometry and (R) +1.0% cf. turbidimetry (n=6) method-group means. PV+/- values were (H versus R) 0.98/0.37 and (H versus B) 0.95/0.65. HemoCue is easy to handle. Results below 20 mg/L need to be confirmed at the central laboratory to exclude microalbuminuria. Values above 20 mg/L can be used to follow microalbuminuria, as precision allows discerning steps of 10 mg/L.

Room temperature deposition of Sn on the Pt(110)(1 x 2) surface has been studied by scanning tunnelling microscopy and core level photoelectron spectroscopy. At low coverage Sri is found in three d ...

The surface properties of SnO 2 (1 1 0)-4×1 and sputtered SnO 2 (1 1 0) were studied comparatively by resonant photoemission of the valence band states in a photon energy range of 60–130 eV. Resonating energetic levels could be observed on the 4×1 reconstructed surface and the resonance behavior could be switched off by sputter treatment. Additionally, the Sn 4d core-levels were recorded at two photon energies in order to allow a statement about the surface's stoichiometry. A tentative explanation of the observed resonance and of the discrepancy between ordered and sputtered surface is given with regard to recent STM results on similar prepared surfaces.

Pd-, Pt-doped and undoped SnO 2 gas sensors were studied by synchrotron radiation photoelectron spectroscopy (SRPES) and laboratory source UPS (ultraviolet photoelectron spectroscopy). Valence band spectra were recorded for photon energies of 60-120 eV (SRPES) and for 40.81 eV (UPS). The spectra were analyzed by factor analysis and generation of difference spectra. A comparison of the samples shows that the doping material of these sensors is not introducing additional states to the surface electronic structure within the limit of detection. This leads to the conclusion that the surfaces of the grains are not enriched with the metal additives.

The electronic properties and the thermal stability of a thin film of lead-phthalocyanine deposited on the InSb(100)-(4 x 2)/c(8 x 2) surface were studied by synchrotron radiation core level and valence band photoelectron spectroscopy. The interaction between the overlayer and the substrate was determined by analyzing the photoemission spectra of a thin film and of a single monolayer of adsorbed molecules. Subsequently the monolayer was annealed at increasing temperatures, leading first to a gradual change of the oxidation state of the central lead atom, then to a fragmentation of the macrocycle itself.

The reconstruction process of SnO 2 (1 1 0) was investigated by scanning tunneling microscopy (STM), low energy electron diffraction (LEED) and X-ray photoelectron spectroscopy (XPS). The high-temperature 1×1 reconstruction could be identified as an intermediate face, transferable either to the 1×2 surface by annealing to higher temperature or back to the 4×1 reconstruction by annealing again at lower temperature. In this way, a new method to prepare well-ordered 4×1 terminated surfaces is introduced and the O/Sn ratio as well as the core-level positions of Sn 3d and O 1s were traced by XPS over a temperature range of 700–1200 K on freshly sputtered and on low-temperature long-time annealed SnO 2 (1 1 0). STM images of the 1×1 surface show a new structure of in-plane oxygen, ordered locally in zigzag rows that contribute to the LEED pattern as a very diffuse 2×1 intensity.

We use hybrid density-functional theory (DFT) and scanning tunneling microscopy (STM) to study oxygen adsorption on the Pt(110) surface. In the STM images oxygen appear as bright protrusions on the ...

The population sample of the Kristianstad survey, a reference intervals survey in the county of Kristanstad, was used to establish new reference intervals in clinical chemistry at the laboratories of the Central Hospital in Kristianstad, the University Hospital in Lund and the University Hospital in Malmö. Three-hundred and fifty nine subjects, male and female, aged 20–80+ years, were invited to participate in the study, with a participation rate of 70 %. Up to 70 analyses were performed on each subject, general clinical chemistry parameters in all three laboratories, specialized analyses where available. Separate a priori exclusion criteria were defined for each test. In addition, the test pattern of each individual was evaluated for signs of preclinical disease. Twelve cases of preclinical disease were discovered and clinically confirmed. Details on all test methods are presented along with information concerning instruments used, calibration procedures, methods of calculation and obtained reference intervals. Although the methods were in general calibrated against acknowledged reference materials, in some instances differences were found that made common reference intervals across all laboratories impossible. Problems relating to the practical use of international recommendations and the establishment of reliable reference intervals are discussed.

One of the main determinants of plasma homocysteine in healthy subjects is serum creatinine. In the present study, we therefore investigated the relation between plasma homocysteine concentration, serum creatinine and a new marker for glomerular filtration rate, plasma cystatin C concentration. Cystatin C reflects the glomerular filtration better than serum creatinine and is not related to the muscle mass and formation of creatinine. The study group consisted of 255 healthy subjects from a well-defined area in the southern part of Sweden. The concentration of plasma homocysteine was increased in men compared to women. This difference disappeared when men and women were stratified by serum creatinine values. Statistically significant correlations were noted between plasma homocysteine and age, plasma cystatin C and serum creatinine. It is shown that plasma homocysteine is not only correlated to serum creatinine as a result of renal function but also as a result of the relationship between homocysteine production and creatine-creatinine synthesis. Using linear regression we were able to show that plasma cystatin C had a higher explanatory value than age. Serum creatinine showed a lower explanatory power than age. The findings in the present study might suggest that the increase of plasma homocysteine concentration with age could be partly due to the deterioration of renal function. Study

The diabetes or impaired glucose tolerance that occurs in most patients with pancreatic cancer is characterized by profound insulin resistance. Recent evidence suggests that the diabetes may result from the presence of the tumor rather than being a predisposing factor to development of the malignancy. Some islet hormones have been shown to exhibit diabetogenic effects. To investigate the potential role of these hormones in the diabetic state associated with pancreatic cancer, we measured islet hormones during fasting in pancreatic cancer patients (n = 30), patients with other malignancies (n = 43), and healthy controls (n = 25). Preoperative pancreatic cancer patients were classified as normal glucose tolerance (NGTT), impaired glucose tolerance (IGTT), non-insulin-requiring diabetes (NIRD), and insulin-requiring diabetes (IRD). Nine pancreatic cancer patients were studied after tumor removal by subtotal pancreatectomy. Some preoperative pancreatic cancer patients (n = 19), postoperative patients (n = 9), and controls (n = 8) were also studied during hyperglycemia and following glucagon injection. Fasting plasma C-peptide was elevated in NIRD pancreatic cancer patients compared to controls. Fasting levels of islet amyloid polypeptide (IAPP), glucagon, and somatostatin were elevated in NIRD and IRD patients. IAPP and glucagon, but not somatostatin, normalized following subtotal pancreatectomy. During hyperglycemia, increases in C-peptide and IAPP were seen only in controls and in NGTT and postoperative pancreatic cancer patients. After glucagon infusion, IAPP levels increased in controls and nondiabetic cancer patients; C-peptide levels increased in controls, nondiabetic patients, and NIRD. Responses of C-peptide and IAPP to glucagon normalized after pancreatectomy. During hyperglycemia, glucagon levels fell in all groups except IGTT patients and a decrease in somatostatin concentrations was seen in controls.

Recent studies have indicated that serum and plasma cystatin C are better markers for glomerular filtration rate (GFR) than serum creatinine, ubiquitously used for this purpose. To fully exploit the value of serum and plasma cystatin C as GFR markers, reliable age and sex-correlated reference intervals are required. The present study comprised cystatin C determinations in plasma and sera from 259 individuals from a well-defined area in the southernmost part of Sweden. From demographic lists two men and two women were randomly selected from each one-year birth cohort above 20 years of age. No sex differences were found for plasma and serum cystatin C, whereas an increase in the cystatin C levels with age was noted, corresponding to the known age-related decrease in GFR. The following reference intervals are recommended for practical clinical use: S-Cystatin C (both sexes): 20-50 years, 0.70-1.21 mg l-1 and 50+ years, 0.84-1.55 mg l-1. The same samples were also used for determination of beta 2-microglobulin levels in order to calculate reference intervals for the beta 2-microglobulin/cystatin C-ratio, which is a more distinct marker for cell proliferation, particularly lymphoproliferation, than is the serum level of beta 2-microglobulin alone, since the ratio should be virtually uninfluenced by GFR. The beta 2-microglobulin/cystatin C-ratios were uninfluenced by sex and age and 1.45-2.43 is recommended as the serum reference interval for practical clinical use. Serum creatinine was determined in the same samples and the creatinine level was found to be strongly influenced by sex and weakly by age.

We have previously reported increased blood glucose concentrations and skeletal muscle glycogen depletion in severe COPD patients with chronic respiratory failure. In order to see if insulin resistance exists in severe COPD, we investigated nine patients with advanced COPD with chronic hypoxaemia and seven healthy control subjects of similar age, using the euglycaemic hyperinsulinaemic glucose clamp technique. We could not demonstrate a subnormal intravenous glucose requirement in response to insulin when maintaining euglycaemia in the COPD patients with chronic hypoxaemia. This indicates that the net metabolism of glucose in COPD patients with chronic hypoxaemia is not resistant to insulin.

We describe a 48-year-old woman with recurrent severe hypoglycaemia apparently caused by a paraprotein with insulin-binding capacity. Very high fasting values were found for serum insulin (170 and > 250 mU l-1) as well as for proinsulin 125 pmol l-1 and an insulinoma was suspected. Hypoglycaemia developed after an oral glucose tolerance (OGTT) test but not during fasting for 48 h. Free insulin and C-peptide were normal during OGTT whereas serum insulin was very high. 125I-insulin binding to serum, determined with a polyethylene glycol (PEG) precipitation method was high (40%), and equally high after addition of 1.7 x 10(-5) mol l-1 cold insulin to estimate non-specific binding. By adding very high concentrations of cold insulin, displacement of 125I-insulin bound to serum was found (50% displacement at 4 x 10(-5) mol l-1). No immunoglobulin G (IgG) insulin antibodies were detected by radioimmunoelectrophoresis. On agarose electrophoresis a small paraprotein (4 g l-1) in the gamma-globulin fraction was detected. 125I-insulin binding to this paraprotein was demonstrated. We conclude that if insulin autoantibodies are suspected as a cause of hypoglycaemia screening for insulin antibodies should always be done with a PEG-precipitation method.

In order to discriminate between transsudated and intrathecally produced IgA and IgM in patients with blood cerebrospinal fluid (CSF) barrier (BCB) damage, we developed extended indices (IgA-EI and IgM-EI) for these immunoglobulins according to the general formula for extended index of a component X in CSF: where a is a parameter specific for X. For IgA parameter a was found to be 1·15 and for IgM 1·9. A preliminary evaluation of IgA-EI and IgM-EI indicated lower false positive rates as compared to CSF IgA and IgM concentrations as well as ‘conventional’ IgA and IgM indices in cases with BCB damage, and essentially the same rates as for the hyperbolic formulae of Reiber and Felgenhauer. The importance of reliable sampling and analytical technique for IgM in CSF is discussed.

Diabetes occurs frequently in patients with pancreatic cancer. To investigate the impact of tumour removal, seven patients were studied before and after 85 per cent subtotal pancreatectomy for adenocarcinoma of the pancreas. The frequency of diabetes was determined by the oral glucose tolerance test. Fasting levels of C peptide and insulin were measured in plasma, and insulin secretion was investigated by hyperglycaemic glucose clamp and glucagon stimulation. Six of the seven patients were diabetic before surgery and four required insulin treatment. Improvements in diabetic status and glucose metabolism were found in all seven patients after operation, as demonstrated by increased glucose metabolic capacity during hyperglycaemia. This occurred despite a postoperative reduction in insulin secretion and is explained by the observed augmentation of whole-body insulin sensitivity after surgery. A diabetogenic factor may be produced by pancreatic adenocarcinoma that may be responsible, directly or indirectly, for the high frequency of diabetes in patients with pancreatic cancer.

The lipoprotein (Lp) pattern was analysed in patients with suspected unstable coronary artery disease (UCAD), to compare the pattern as a prognostic instrument regarding subsequent coronary events with smoking, hypertension, diabetes mellitus and with the result of an early exercise test. Included were 295 patients with UCAD. Blood samples for Lp values were obtained in the acute phase and after one year. Apolipoprotein-A1, Apolipoprotein-B (Apo-B), Lipoprotein(a) (Lp[a]) HDL-Cholesterol, Cholesterol (Chol) and Triglycerides (TG). were estimated in serum. During the 1-year follow-up coronary events (myocardial infarction, cardiac death, coronary artery by-pass surgery) occurred in 48 patients. The severity of CAD, overweight, smoking and beta-blockade influenced the Lp-pattern. Chol-, TG- and Apo-B-levels were highest in the group with a coronary event. Apo-B turned out to be the second best predictive variable in multiple regression analysis, in men. In women no such analysis was done because of very few coronary events during follow-up. Nevertheless, the exercise test variables, ST depression and pain were more predictive of coronary events than Apo-B in men.

In elderly individuals the saliva production is often decreased, leading to dry mucosal membranes and predisposition to local infections, as well as other oral problems. Eighty-five hospitalized geriatric patients, with a multitude of disabling diseases, participated in a double blind placebo-controlled study when mucin-containing artificial saliva and a placebo liquid was given. In the patients treated with the artificial saliva a considerable improvement in the condition of oral mucosa was seen. Also, in one quarter of the patients treated with the placebo liquid, the oral candida infection disappeared, possibly due to improved oral hygiene. It is reasonable to assume that general well-being increases when the condition of the oral mucosa improves. If factors causing dry mouth cannot be removed, i.e. due to diseases or ageing factors, treatment with artificial saliva could be of benefit, but the importance of good oral hygiene must not be overlooked.

Four analytical methods for plasma D-dimer have been compared in a group of 82 consecutive patients with suspected venous thrombosis, 22 of whom subsequently received a positive clinical diagnosis. Differences in diagnostic power between methods were observed. In three of the four methods tested, the use of elevated discriminatory limits (rather than conventional 95-percentile upper reference limits) resulted in stronger positive predictive values for thromboembolism. We suggest that this approach may result in better diagnostic performance of the D-dimer method.

A new reagent carrier, Reflotron® ALP, has been developed for the Reflotron® system, allowing easy and rapid measurement (in less than 3 minutes) of alkaline phosphatase (ALP) activity in capillary blood, venous blood, heparinized plasma or serum. The evaluation of the analytical performance of the assay was carried out at eight clinical laboratories. The study of the imprecision using the measurements in human samples resulted in coefficients of variation ranging from 1.3% to 4.6% (within-run) and from 3.2% to 4.0% (day-to-day). The analytical specificity of the Reflotron® ALP assay agrees well with ALP methods using a N-methyl-D-glucamine buffer solution. The calibration of the Reflotron® ALP assay, however, is related to the reference intervals for ALP methods using a diethanolamine buffer solution. Method comparisons were performed with the ALP method on Hitachi instruments using diethanolamine buffer. Reflotron® ALP measurements in blood and plasma in 157 randomly selected split samples showed excellent agreement (slope: 0.99; intercept: 0.7 U/I; median bias: 2.3%; median difference from the comparison method: -0.3%), Specimens from pregnant women and adolescents were excluded from this study. Differing values were obtained in a method comparison using 48 samples containing predominantly the ALP bone isoform (slope: 0.81; intercept: 31.5 U/I; median bias: 5.7%; median difference from the comparison method: -12.2%). Regression analysis of the results from 21 sera with prevailing placental ALP gave a slope of 1.51, and an intercept of -41.1 U/I (median bias: 8.6%; median difference from the comparison method: 35.6%). Reflotron® ALP was compared with three different wet chemistry procedures using different buffer compounds: N-methyl-D-glucamine or diethanolamine or 2-amino-2-methyl-1-propanol. In samples containing predominantly ALP isoforms not of liver origin, the measurements with N-methyl-D-glucamine buffer gave the best fit with respect to Reflotron®. In an interference study with 18 drugs, no effect on the test results could be detected. Total bilirubin up to 750 μmol/l and hemolysis up to 1.7 g/l free hemoglobin did not influence the test. Reflotron® ALP proved to be an easy and rapid method with excellent precision. The accuracy related to an ALP method using diethanolamine buffer was good. The systematic differences for ALP in samples from pregnant women and adolescents have to be taken into account. The assay is well suited for differential diagnosis of hepatic diseases in decentralized testing.

The population sample of the Kristianstad survey, a reference intervals survey in the county of Kristianstad, was used to establish new reference intervals in clinical chemistry at the laboratories of the Central Hospital in Kristianstad, the University Hospital in Lund and the University Hospital in Mälmo. Three-hundred and fifty nine subjects, male and female, aged 20-80+ years, were invited to participate in the study, with a participation rate of 70%. Up to 70 analyses were performed on each subject, general clinical chemistry parameters in all three laboratories, specialized analyses where available. Separate a priori exclusion criteria were defined for each test. In addition, the test pattern of each individual was evaluated for signs of preclinical disease. Twelve cases of preclinical disease were discovered and clinically confirmed. Details on all test methods are presented along with information concerning instruments used, calibration procedures, methods of calculation and obtained reference intervals. Although the methods were in general calibrated against acknowledged reference materials, in some instances differences were found that made common reference intervals across all laboratories impossible. Problems relating to the practical use of international recommendations and the establishment of reliable reference intervals are discussed.

To characterize its insulin-antagonistic effect, growth hormone (GH) was infused at variable rates (24, 12 or 6 mU kg-1 min-1) for 1 h in 7 IDDM patients. Saline infusion was used as control (C) and all patients participated in all studies. The effect of insulin was measured with the euglycaemic clamp technique for 6 h combined with d-(3-3H)-glucose to evaluate glucose turnover. The insulin levels during the clamps were similar in all studies (23 +/- 3 mU l-1). The infusions produced peak GH levels of (24 rate = 24) 157 +/- 11, (12 rate = 12) 76 +/- 7, and (6 rate = 6) 45 +/- 8 mU l-1 (mean +/- SEM). The insulin-antagonistic effect of GH on glucose uptake was seen after 2 h and was at a maximum 4 to 5 h after the start of the GH infusion (difference in glucose infusion rate between C and 24 was 1.7 +/- 0.4 mg kg-1 min-1, p < 0.01). The resistance was due to a less pronounced effect of insulin to both inhibit rate of appearance and to stimulate rate of disappearance. Infusion of GH at 12 mU kg-1 min-1 induced a less pronounced insulin resistance both with regards to maximal effect (glucose infusion rate C - GH 1.4 +/- 0.5 mg kg-1 min-1, p < 0.05) and duration (3 h). At 6 mU kg-1 min-1, a clear GH-induced insulin-antagonistic effect was only seen during the third hour of the clamp (glucose infusion rate C-GH 1.3 +/- 0.5 mg kg-1 min-1, p < 0.05). GH infusion impaired the effect of insulin to lower both the levels of free fatty acids (NEFA) and glycerol between 2 and 5 h after the start of the infusion (NEFA, C:110 +/- 29, 24:303 +/- 95, p < 0.05: glycerol, C:32 +/- 4, 24:50 +/- 7 mumol l-1, p < 0.05). The present study therefore demonstrates that the insulin-antagonistic effect of GH in IDDM is related to the plasma levels both with regard to duration and response. The results also indicate that GH impairs the effect of insulin on lipolysis in IDDM after physiological peaks.

The aim of the present study was to characterize the effect of 44 h of hyperglycaemia on diurnal levels of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-1 (IGF-1), growth hormone (GH) and glucagon in 7 well-controlled subjects with insulin-dependent diabetes mellitus (IDDM). Hyperglycaemia (approximately 15 mmol/l) was induced by a glucose infusion, while the degree of insulinisation was similar to that of a corresponding period with near normoglycaemia (approximately 6.9 mmol/l). Hyperglycaemia for 44 h did not alter the normal diurnal IGFBP-1 levels when the degree of insulinisation was unchanged. The diurnal secretion pattern of IGFBP-1 was preserved in both genders and without any difference between the control and hyperglycaemic periods. However, the IGFBP-1 levels were increased in these IDDM subjects despite a peripheral hyperinsulinemia. An inverse correlation was found between IGFBP-1 and peripheral insulin levels both during periods of rapid changes in IGFBP-1 and insulin concentrations (i.e. morning hours) as well as during the total 24-h sampling period. Total IGF-1 levels were low, but no further decrease was seen after 24 h of hyperglycaemia in the presence of unchanged insulin levels. In conclusion, the present study clearly shows that the increased IGFBP-1 level seen during poor metabolic control in IDDM is not caused by hyperglycaemia. Glucose levels per se do not influence either total IGF-1 or IGFBP-1 concentrations in well-insulinised diabetic patients.

Objectives. Insulin treatment of patients with type 2 diabetes causes hyperinsulinaemia and improves glycaemic control. We have studied how this affects risk factors for cardiovascular disease. Design. Patients with secondary failure to oral hypoglycaemic agents were studied whilst still taking oral agents and after insulin treatment for 8 weeks in an open study. Setting. Department of Internal Medicine, University Hospital, Linkoping. Subjects. Ten consecutive patients with type 2 diabetes and secondary failure to oral hypoglycaemic agents. Interventions. Switching oral treatment to insulin treatment. Main outcome measures. Effect on several cardiovascular risk factors. Results. Fasting and postprandial plasma insulin concentrations were increased by insulin treatment whereas C-peptide concentrations were lowered. HbAlc was reduced from 8.9 ± 0.3% (mean ± SEM) to 6.3±0.2% after 8 weeks. There was a weight gain of 2.8±0.7 kg. Plasma concentrations of total- and very-low-density-lipoprotein (VLDL) cholesterol, VLDL-, low density lipoprotein and high-density-lipoprotein triglycerides were all reduced. The plasma concentration of apolipoprotein B was also lowered. Tissue plasminogen activator antigen measured after venous occlusion showed a significant reduction whilst plasminogen activator inhibitor 1 activity was 26.0±9.8 IU ml-1 on oral treatment and 18.2±4.7 IU ml-1 on insulin treatment (NS). Albumin excretion in the urine was reduced and the percentage reduction correlated with the percentage lowering of the tissue plasminogen activator antigen concentration after venous occlusion but not with the percentage change of basal tissue plasminogen activator antigen concentration. Conclusions. Insulin treatment of patients with type 2 diabetes and secondary failure to oral hypoglycaemic agents causes hyperinsulinaemia and improves or has no unfavourable effect on several cardiovascular risk factors.

Objectives. The acute effect of smoking and snuffing on insulin sensitivity was studied in a group of healthy habitual smokers. Design The euglycaemic clamp technique was combined with the subcutaneous injection of a bolus (0.1 U kg−1) of fast-acting insulin (Actrapid®). Randomized subjects smoked either one cigarette per hour for 6 h, took one bag-packed snuff per hour for 6 h or refrained from nicotine for 48 h before as well as during the clamp. Subjects. Seven healthy smokers, four females and three males, of normal weight (BMI, mean ± SKM. 21 ± 0.7 kg m−2 with a range of 18.6–23.9), aged 31 ± 2 years (range 24–35 years), who had consumed at least 20 cigarettes per day for at least 5 years were studied. They were recruited through an advertisement in a newspaper. Results. The steady-state plasma nicotine levels were similar during smoking and snuffing. The insulin and glucose levels were also similar during all three clamps. Smoking, but not snuffing, impaired insulin action (P < 0.05) mainly due to a lower peripheral glucose uptake. The mean growth hormone levels during the 6-h study were more than doubled during smoking (P < 0.01) while no significant differences were seen in the other counter-regulatory hormones. Conclusion. Smoking (also in habitual smokers) acutely impairs insulin action and leads to insulin resistance. Thus, smoking can be of importance for the development of the insulin resistance syndrome associated with risk for cardiovascular disease.

Blood glucose profiles, fasting blood glucose and glycated haemoglobin were followed prospectively for 6 weeks in 14 patients with non-insulin-dependent diabetes (NIDDM). Capillary blood glucose was sampled weekly on filter paper and analysed in the laboratory. Glycated haemoglobin was determined every other week with both cation-exchange chromatography (HbA1-IEC) and aminophenylboronic acid affinity chromatography (GHb-PBA). The mean for the blood glucose profiles was 11.2 +/- 3.5 mmol l-1 (+/- SD) and the mean for fasting blood glucose was 9.5 +/- 2.8 mmol l-1. For individual patients the differences between mean fasting blood glucose and mean blood glucose varied from -1.3 to 4.2 mmol l-1. There was a linear relationship between blood glucose and glycated haemoglobin which was steeper for GHb-PBA than for HbA1-IEC. The correlations with fasting blood glucose and mean blood glucose for HbA1-IEC were r = 0.85 and r = 0.92 and for GHb-PBA r = 0.87 and r = 0.96 respectively. Mean blood glucose was better correlated to glycated haemoglobin than fasting blood glucose (p < 0.05 for GHb-PBA).

The aim of the present study was to characterize the effect of a hyperglycemic period (44 hours) on the levels of insulin-antagonistic hormones and insulin sensitivity in seven subjects with well-controlled insulin-dependent diabetes mellitus (IDDM). Hyperglycemia (approximately 15 mmol.L-1) was induced by a glucose infusion while the degree of insulinization was similar to that of the period with near normoglycemia (approximately 6.9 mmol.L-1). Insulin sensitivity was measured with hyperinsulinemic euglycemic clamps performed 4 hours before and after the periods of normoglycemia (control) and hyperglycemia. D-[3-3H]glucose was infused in the second clamp in each study to evaluate glucose production and utilization. Since growth hormone (GH) levels frequently are elevated during poor diabetic control, diurnal GH secretion was measured in blood samples continuously drawn for 24 hours during the euglycemic and hyperglycemic periods. Levels of epinephrine, norepinephrine, cortisol, and nonesterified free fatty acids (NEFA) were similar during the control and hyperglycemic periods and during the clamps. GH levels were also similar, but an abnormal diurnal secretion pattern was present with increased numbers of daytime peaks. Hyperglycemia did not reduce GH secretion in IDDM. Hyperglycemia for 44 hours induced insulin resistance (32% reduction of glucose infusion rate, P < .02). In the control study, a 21% reduction (P = .064, NS) of the glucose disposal rate (Rd) was seen, suggesting that the hospitalization period per se may also reduce insulin sensitivity. In conclusion, a period of hyperglycemia leads to insulin resistance in IDDM patients. This insulin resistance cannot be attributable to increased levels of insulin-antagonistic hormones, although an abnormal secretion pattern for GH was found.(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate glucose metabolism and insulin secretion on patients with pancreatic cancer compared with healthy control subjects.Open study.Linköping University Hospital, Sweden.44 consecutive patients referred for radical operations for pancreatic carcinoma, and eight healthy age and sex matched volunteers.Hyperglycaemic glucose clamp in 36 of patients and all volunteers.Glucose tolerance according to WHO criteria, plasma insulin and C-peptide concentrations, and insulin secretion measurements both during hyperglycaemia and after stimulation by glucagon.Thirty-three patients (75%) had either impaired glucose tolerance or diabetes. Fasting insulin concentrations were raised in the non-insulin-requiring diabetic patients, but similar in the insulin-requiring group compared with healthy control subjects and patients with normal glucose tolerance. In neither diabetic group was insulin secretion affected during hyperglycaemia. After stimulation with glucagon, insulin secretion increased in non-insulin-requiring diabetic patients but remained unchanged in those who required insulin. Glucose metabolic capacity and whole body insulin sensitivity were reduced in patients with diabetes and with impaired glucose tolerance, and the reduction was more pronounced in diabetic patients.There is a high incidence of impaired glucose tolerance and diabetes in patients with pancreatic cancer, which cannot be explained by impaired secretion of insulin. Other factors that reduce insulin sensitivity seem to have a role in the development of diabetes in this group of patients.

The insulin-antagonistic effects of pulsatile (3 min pulses every 20 min) and continuous glucagon infusions were studied over 4 h with the euglycemic clamp technique in healthy subjects. Comparisons were made to the effect of a continuous adrenaline infusion. Glucose production and utilization were evaluated with D-3-3H-glucose and somatostatin was used in all studies to inhibit the endogenous release of insulin and glucagon. The amount of glucagon given during the pulsatile infusions (27% of that during continuous infusion) was adjusted so that the peak glucagon levels were the same as during the continuous infusion (372 +/- 22 and 365 +/- 20 ng/L, respectively). The insulin-antagonistic effects of pulsatile and continuous glucagon infusions were similar during the first hour and imparied the insulin effect with 44 +/- 8 and 47 +/- 6%, respectively. However, when infused continuously, the effect of glucagon declined rapidly, whereas the effect of a pulsatile infusion decreased more slowly and was evident for 3 h. Raising the glucagon level 4-fold restored the insulin-antagonistic effect again suggesting that the cells had become desensitized. In contrast, the insulin-antagonistic effect of adrenaline was persistent throughout the 4 h of the study and impaired insulin action with 54 +/- 2%. The effects of pulsatile and continuous glucagon infusions were entirely due to the stimulation of glucose production while that of adrenaline mainly was due to inhibition of peripheral glucose uptake. In conclusion, the acute stimulatory effect of glucagon on glucose production is transient but it is better maintained when given as intermittent pulses rather than as a continuous infusion. In contrast, the insulin-antagonistic effect of adrenaline on glucose uptake is persistent for at least 4 h.

The insulin-antagonistic effect of growth hormone was characterized by infusing the hormone at three different infusion rates (6, 12 or 24 mU·kg−1·min−1) for one h in 11 healthy subjects. The insulin effect was measured with the euglycaemic clamp technique combined with D-(3-3H)-glucose infusion to evaluate glucose production and utilization. A control study with NaCl (154 mmol·l−1) infusion was also performed. The insulin levels during the clamps were similar in all studies (36±0.2 mU·l−1). Peak growth hormone levels were reached at 60 min (growth hormone 6mU·kg−1·h−1: 31±5; growth hormone 12 mU·kg−1·h−1: 52±4 and growth hormone 24 mU·kg−1·h−1: 102±8mU·l−1). The insulin-antagonistic effect of growth hormone started after ∼2 h, was maximal after 4–5 h (∼39% inhibition of glucose infusion rate between control and growth hormone 24 mU·kg−1·h−1) and lasted for 6–7 h after peak levels. The resistance was due to a less pronounced insulin effect both to inhibit glucose production and to stimulate glucose utilization. Growth hormone infusion of 12 mU·kg−1·h−1 induced a similar insulin-antagonistic effect as the higher infusion rate whereas 6 mU·kg−1·h−1 induced a smaller response with a duration of 1 h between 3–4 h after peak levels of growth hormone. The present study demonstrates that growth hormone levels similar to those frequently seen in Type 1 (insulin-dependent) diabetic patients during poor metabolic control or hypoglycaemia, have pronounced insulin-antagonistic effects. The effects starts after about 2–3 h, is maximal after 4–5 h and lasts for about 6–7 h. Both duration and inhibitory effect of growth hormone are related to the plasma levels, where a maximal effect is seen at about 50 mU·l−1 or higher.

The aims of the study were to investigate the relationship between nutritional state and the development of pressure sores and to test the hypothesis that supplementary nutritional support might prevent pressure sore development and improve healing. Newly admitted long-term care patients hospitalised for more than 3 weeks were included and randomised into an experimental and a control group. The nutritional state was evaluated using serum protein analyses, anthropometry and the delayed hypersensitivity skin test. Further, the patients' condition was assessed weekly using a modified Norton scale. The experimental group received extra nutritional support. Significantly more patients with protein-energy malnutrition had, or developed, pressure sores. Regression analyses indicated albumin, mobility, activity and food intake as predictors for pressure sores. Patients who received extra nutritional support tended to develop fewer pressure sores and to heal existing pressure sores to a greater extent than the control group, although this did not reach statistical significance.

The prevalence of protein-energy malnutrition (PEM) was examined in 1206 randomly selected elderly people aged 65 to 80 years living in their own homes. Nutritional assessment was based on weight loss, weight index, triceps skin fold, arm muscle circumference, serum albumin and prealbumin, and delayed cutaneous hypersensitivity (DCH) reaction. The prevalence of PEM was 5 per cent. If people with signs of inflammation were excluded, the prevalence of PEM was 3.5 per cent. When other nutritional indices, used by other authors among hospitalized patients, were applied to our sample prevalence values from 2.6 to 4.1 per cent were obtained. the prevalence was not related to sex or age. DCH increased the sensitivity of the screening method but causes of anergy other than PEM must be taken into account. It is concluded that PEM, in a degree shown to impair the prognosis at hospital, does occur among elderly people at home in an industrialized country.

Plasma selenium was determined pre-operatively and during 10 days of TPN in 21 Swedish patients presenting for major surgery. Pre-operative hyposelenaemia was found in five patients, and was significantly related to the presence of an inflammatory response (CRP ⩾= 100 mg/l). There was a significant negative correlation (r = −0.58, p

The importance of a short-term elevation of the ambient glucose level for the release of counter-regulatory hormones and the glucose recovery rate during a subsequent hypoglycaemia was studied in healthy subjects. Hypoglycaemia was induced with insulin infusion after a previous 80 min of euglycaemic (E: 5 mmol/l) or hyperglycaemic (H: 15 mmol/l) glucose clamp. By infusing insulin during the euglycaemic clamp similar levels were reached during both glucose clamps. The same level of hypoglycaemia was reached in both studies (E: 1.5 ± 0.1, H: 1.5 ± 0.2 mmol/l) and the insulin levels were also similar both at glucose nadir and during the recovery period. In spite of this, both the mean glucagon levels at nadir at the mean individual maximal increase were significantly lower after the hyperglycaemic clamp (E: 101 ± 25, H: 54 ± 7 pg/ml, P < 0.05). The glucose recovery rate was also significantly impaired following the hyperglycaemic clamp. The results show that a short-term elevation of the ambient glucose level impairs the glucagon release during a subsequent hypoglycaemia. This finding may be of importance for the development of the blunted glucagon release in response to low glucose levels in diabetics.

Hemoglobinometry according to the International Committee of Standardization in Hematology (ICSH) suffers from imprecision related to high sample dilution and from potential errors owing to sample turbidity. We have evaluated a new instrument, "HemoCue," that measures hemoglobin at two wavelengths as azide methemoglobin, without dilution. The HemoCue method is superior to the ICSH method: by correction for turbidity, it avoids false hemoglobin readings that may arise from hyperlipemia or some large M-component of the immunoglobulin M class. We find the equipment suitable for use in outpatient units.

Two patients with macroglobulinemia, one with a monoclonal IgA and the other with a monoclonal IgM, are described. In connection with cytostatic treatment and infection both patients got very high CRP-concentrations as measured by laser nephelometry. These seemed to be caused by C-reactive protein immunoglobulin complex formation as determined by immunofixation.

In a randomised, double-blind, cross over trial, 25 patients with mild to moderate primary hypertension were given nifedipine 20-40 mg twice daily and labetalol 200-400 mg twice daily after a 4 week period on placebo, followed by the two drugs in combination. The BP during placebo therapy was 164/108 mmHg supine and 159/110 mmHg standing. After monotherapy with nifedipine for 6 weeks the supine BP was reduced by 18/13 mmHg and the standing BP by 20/12 mmHg; with labetalol the corresponding figures were 26/15 mmHg and 28/21 mmHg, respectively. The combined therapy induced a larger fall in BP, by 36/22 mmHg supine and by 39/24 mmHg standing; in 21 of 23 patients the BP became normal. The heart rate (HR) decreased during labetalol treatment alone and on the combined therapy. With nifedipine alone, the HR was unchanged in the supine position and increased on standing. Nifedipine increased plasma renin activity (PRA) and urinary aldosterone excretion (uA), whereas labetalol reduced both. During combination therapy, PRA and uA remained unchanged. There was a slight fall in HDL-cholesterol during treatment with labetalol alone and in combination with nifedipine. The fasting blood glucose increased slightly during treatment with each of the drugs, but neither caused a change in the concentrations of glycosylated haemoglobin A1, serum insulin, C-peptide, or plasma glucagon. Adverse effects as a rule were well tolerated and were related to the pharmacological effects of the drugs. Only 2 patients left the trial, both during labetalol treatment.

We evaluated the effect of sampling of capillary blood on filter paper on the later analysis for glucose. We found the method simple and reliable. Determination at the central laboratory of glucose in blood collected onto filter paper and comparison of the results with those obtained with test strips read in reflectometers at outpatient units is easy. Collecting duplicate samples on filter paper facilitates quality control by avoiding the complications that arise from using quality-control solutions that are not directly comparable with fresh blood, and it avoids the disturbances of test strip chemistry attributable to the glycolysis inhibitors added to blood samples intended for quality control.