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P Nuutila

Publications and source records attributed to P Nuutila.

18 recordsLinked to original sources
PubMed1995

The effect of insulin and FFA on myocardial glucose uptake.

In addition to direct stimulation of glucose uptake and metabolism in cardiac myocytes, insulin inhibits lipolysis and, thereby, reduces serum free fatty acid (FFA) concentrations. This, in turn, has been suggested to enhance myocardial glucose utilization. To study the mechanism of insulin action on myocardial glucose uptake (MGU) in vivo, five patients with stable coronary artery disease were studied with positron emission tomography (PET) and [18F]FDG. All patients underwent two PET studies after a 12-h fast, once during low serum FFA but high insulin concentrations (during insulin clamp), and once during low serum FFA and low insulin concentrations (in the fasting state after two oral doses of 250 mg of an antilipolytic drug, acipimox). The MGU in the normal myocardium was measured using dynamic PET imaging. Plasma glucose concentrations were comparable during the insulin clamp and after administration of acipimox (5.0 +/- 0.4 v 5.2 +/- 0.3 mmol/l, n.s.). Serum insulin concentrations were high during clamp but remained in low fasting concentrations after acipimox (74 +/- 9 mU/l v 6 +/- 5 mU/l, P = 0.0001). Serum FFA concentrations were similar during both approaches (230 +/- 110 v 200 +/- 40 mumol/l, respectively, n.s.). No difference in cardiac work load was detected between the approaches. The calculated MGU values in normal myocardium were similar during both approaches (57 +/- 23 mumol/min/100 g v 61 +/- 14 mumol/min/100 g, respectively, n.s.). The MGU values correlated inversely to serum FFA concentration (r = -0.87, P = 0.001) and directly to myocardial work load (r = 0.73, P = 0.016) but not to serum insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Insulin action on heart and skeletal muscle glucose uptake in essential hypertension.

Essential hypertension is characterized by skeletal muscle insulin resistance but it is unknown whether insulin resistance also affects heart glucose uptake. We quantitated whole body (euglycemic insulin clamp) and heart and skeletal muscle (positron emission tomography and 18F-fluoro-2-deoxy-D-glucose) glucose uptake rates in 10 mild essential hypertensive (age 33 +/- 1 yr, body mass index 23.7 +/- 0.8 kg/m2, blood pressure 146 +/- 3/97 +/- 3 mmHg, VO2max 37 +/- 3 ml/kg per min) and 14 normal subjects (29 +/- 2 yr, 22.5 +/- 0.5 kg/m2, 118 +/- 4/69 +/- 3 mmHg, 43 +/- 2 ml/kg per min). Left ventricular mass was similar in the hypertensive (155 +/- 15 g) and the normotensive (164 +/- 13 g) subjects. In the hypertensives, both whole body (28 +/- 3 vs 44 +/- 3 mumol/kg per min, P < 0.01) and femoral (64 +/- 11 vs 94 +/- 8 mumol/kg muscle per min, P < 0.05) glucose uptake rates were decreased compared to the controls. In contrast, heart glucose uptake was 33% increased in the hypertensives (939 +/- 51 vs 707 +/- 46 mumol/kg muscle per min, P < 0.005), and correlated with systolic blood pressure (r = 0.66, P < 0.001) and the minute work index (r = 0.48, P < 0.05). We conclude that insulin-stimulated glucose uptake is decreased in skeletal muscle but increased in proportion to cardiac work in essential hypertension. The increase in heart glucose uptake in mild essential hypertensives with a normal left ventricular mass may reflect increased oxygen consumption and represent an early signal which precedes the development of left ventricular hypertrophy.

Adult↗
PubMed1995

Gender and insulin sensitivity in the heart and in skeletal muscles. Studies using positron emission tomography.

Good insulin sensitivity is independently associated with a low risk for coronary heart disease, but it is unclear whether this risk factor differs between men and women. We compared insulin sensitivity of glucose uptake directly in muscle and heart tissues between healthy women (age 29 +/- 2 years, body mass index [BMI] 22 +/- 1 kg/m2, VO2max 39 +/- 4 ml.kg-1.min-1) and men matched for age (31 +/- 2 years), BMI (23 +/- 1 kg/m2), and VO2max (44 +/- 3 ml.kg-1.min-1) using [18F]fluoro-2-deoxy-D-glucose and positron emission tomography under hyperinsulinemic (insulin infusion rate 1 mU.kg-1.min-1) normoglycemic conditions. Whole body insulin sensitivity was 41% greater in women (52 +/- 6 mumol.kg body wt-1.min-1) than in men (37 +/- 3 mumol.kg body wt-1.min-1, P < 0.05). This difference was explained by a 47% greater rate of glucose uptake by femoral muscles (113 +/- 10 vs. 77 +/- 7 mumol.kg muscle-1.min-1, women vs. men, P < 0.01). Insulin-stimulated glucose uptake rates in the heart were similar in women (738 +/- 58) and men (749 +/- 62 mumol.kg muscle-1.min-1). Femoral muscle insulin sensitivity was closely correlated with whole body insulin sensitivity (r = 0.84, P < 0.001). Gender and VO2max together explained 68% of the variation in femoral muscle glucose uptake. We conclude that women are more sensitive to insulin than equally fit men because of enhanced muscle but not heart insulin sensitivity.

Adult↗
PubMed1995

Free thyroid hormones and a third-generation TSH assay in the detection of hyperthyroidism during long-term thyroxine treatment in thyroid carcinoma patients.

We evaluated the value of serum-free thyroid hormone and thyrotropin (TSH) concentrations in the detection of peripheral hyperthyroidism during thyroxine suppression therapy. A total of 57 patients on a stable thyroxine dose and 70 controls participated in the study. Serum-free thyroxine (FT4), free triiodothyronine (FT3) and TSH were measured by immunoassays based on time-resolved fluorescence (Delfia). The assay for TSH was a modification of a third generation Delfia hTSH Ultra method. The patients were classified into euthyroid and hyperthyroid subgroups based on clinical signs and symptoms (Wayne index). Systolic time intervals (STI) were measured. The Wayne indices were higher among patients than controls (p < 0.0001). The STI results were similar in patients and controls. Only FT4 had the discriminatory power for classifying euthyroid and hyperthyroid patients according to discriminant analyses. The diagnostic value of FT4 was further assessed by calculating the area under the relative operating characteristic (ROC) curve. The area was 0.707 (SE 0.0918), which was significantly different from an area of 0.5, i.e. the area of a test of no value (p = 0.032). In conclusion, a high serum FT4 concentration indicates hyperthyroidism during long-term thyroxine treatment among thyroid carcinoma patients. Although the degree of TSH suppression can now be exactly monitored with new third generation TSH assays, hyperthyroidism cannot be defined using TSH concentration in thyroid carcinoma patients. Therefore, additional serum FT4 concentration assays are needed in the assessment of hyperthyroidism associated with TSH suppression therapy in thyroid carcinoma patients.

Adult↗
PubMed1994

Effect of antilipolysis on heart and skeletal muscle glucose uptake in overnight fasted humans.

We quantitated how lowering of free fatty acid (FFA) by an antilipolytic agent (acipimox) in the fasting state changes glucose uptake in heart and skeletal muscles. Glucose uptake in these tissues was measured two times in seven normal subjects, once after acipimox and once after placebo, using positron emission tomography-derived [18F]fluoro-2-deoxy-D-glucose kinetics. Plasma glucose and insulin remained at their fasting concentrations in both studies. Fasting FFA concentrations were 60% lower after acipimox (238 +/- 39) than placebo (645 +/- 78 mumol/l, P < 0.001). Glucose uptake increased 6 +/- 2-fold in the heart by acipimox (344 +/- 49 vs. 108 +/- 40 mumol.kg muscle-1.min-1, P < 0.002) and 1.5-fold in arm muscles (27.7 +/- 2.6 vs. 18.6 +/- 1.2 mumol.kg muscle-1.min-1, P < 0.02). Heart (r = -0.93, P < 0.001) and arm (r = -0.82, P < 0.001) glucose uptakes were inversely related to serum FFA. We conclude that serum FFA are inversely related to glucose uptake in heart and arm skeletal muscles after an overnight fast. These data indicate that compensatory glycogenolysis, although it may occur, does not prevent operation of the glucose-FFA cycle under fasting conditions.

Adult↗
PubMed1992

Glucose-free fatty acid cycle operates in human heart and skeletal muscle in vivo.

Positron emission tomography permits noninvasive measurement of regional glucose uptake in vivo in humans. We employed this technique to determine the effect of FFA on glucose uptake in leg, arm, and heart muscles. Six normal men were studied twice under euglycemic hyperinsulinemic (serum insulin approximately 500 pmol/liter) conditions, once during elevation of serum FFA by infusions of heparin and Intralipid (serum FFA 2.0 +/- 0.4 mmol/liter), and once during infusion of saline (serum FFA 0.1 +/- 0.01 mmol/liter). Regional glucose uptake rates were measured using positron emission tomography-derived 18F-fluoro-2-deoxy-D-glucose kinetics and the three-compartment model described by Sokoloff (Sokoloff, L., M. Reivich, C. Kennedy, M. C. Des Rosiers, C. S. Patlak, K. D. Pettigrew, O. Sakurada, and M. Shinohara. 1977. J. Neurochem. 28: 897-916). Elevation of plasma FFA decreased whole body glucose uptake by 31 +/- 2% (1,960 +/- 130 vs. 2,860 +/- 250 mumol/min, P less than 0.01, FFA vs. saline study). This decrease was due to inhibition of glucose uptake in the heart by 30 +/- 8% (150 +/- 33 vs. 200 +/- 28 mumol/min, P less than 0.02), and in skeletal muscles; both when measured in femoral (1,594 +/- 261 vs. 2,272 +/- 328 mumol/min, 25 +/- 13%) and arm muscles (1,617 +/- 411 to 2,305 +/- 517 mumol/min, P less than 0.02, 31 +/- 6%). Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.75, P less than 0.005), and arm muscles (r = 0.69, P less than 0.05) but not with glucose uptake in the heart (r = 0.04, NS). These data demonstrate that the glucose-FFA cycle operates in vivo in both heart and skeletal muscles in humans.

Adult↗
PubMed1992

Cardiac systolic time intervals and thyroid hormone levels during treatment of hypothyroidism.

This study was undertaken to compare results of modern serum thyroid hormone assays with cardiac systolic time intervals (STI) during thyroxine treatment in hypothyroid patients. The patients were assessed clinically (Billewicz index) and the STI and serum thyrotropin (TSH), total and free thyroxine (T4) and total and free triiodothyronine (T3) were determined in 16 hypothyroid women (Group I) treated with 50 micrograms increments of thyroxine, and in 13 women who had a history of thyroid carcinoma and high-dose thyroxine replacement therapy and had elevated thyroid hormone concentrations (Group II). The STI of 24 matched healthy female controls were used for reference of STI. The pre-ejection period (PEP) index and the PEP/LVET ratio (left ventricular ejection period) were greater in untreated overtly and mildly hypothyroid patients (p less than 0.05) than in the controls. During stable thyroxine therapy [mean daily dosage for Group I 137.5 (7.3) micrograms and for Group II 220 (61) micrograms] the PEP correlated with serum free T4 (FT4), as measured by a two-step method (SpectriaR) (r = -0.55, p less than 0.01, n = 29) and total T4 (r = -0.51, p less than 0.05, n = 29), but not with TSH, T3, FT3 or FT4 measured by an analogue method Amerlex-M(R). The TRH test was not valuable in follow-up because of the strong correlation between basal TSH and stimulated TSH values (r = 0.95). In conclusion, STI are useful for assessment of the thyroid state in untreated hypothyroid patients. Serum TSH becomes normal in the same time as STI and is the best for follow-up. If serum TSH is low and the patient is on stable thyroxine therapy, we recommend serum FT4 for monitoring thyroxine replacement. Two-step FT4 assays had the best correlation with STI, which has significance in patients with non-thyroidal illness.

Adolescent↗
PubMed1992

Euglycemic hyperinsulinemic clamp and oral glucose load in stimulating myocardial glucose utilization during positron emission tomography.

To enable assessment of myocardial viability, myocardial glucose utilization has commonly been stimulated by oral glucose loading. To compare the effects of glucose loading and insulin and glucose infusion (insulin clamp) on PET fluorodeoxyglucose ([18F]FDG) myocardial scan image quality and regional myocardial glucose utilization rate (rMGU), eight patients with angiographically documented coronary artery disease and previous myocardial Q-wave infarction were studied twice, once during insulin clamp and once 1 hr after oral glucose loading. The rMGU rates were derived by graphic Patlak analysis in 33 normal, 10 scar and 6 "hot spot" myocardial segments. Infusion of insulin and glucose gave stable plasma-glucose and serum-insulin levels during imaging. In contrast, glucose loading caused marked changes in plasma-glucose and insulin concentrations. The image quality was clearly superior and the fractional utilization rates of [18F]FDG were twice as high during insulin clamp than after glucose loading (p less than 0.0001). Due to the higher plasma-glucose levels after glucose loading, the calculated rMGU in normal, scar and hot spot myocardial segments was comparable between the two protocols. The insulin clamp technique makes it possible to adjust and maintain a metabolic steady state during the PET study. It does not alter [18F]FDG uptake patterns in different myocardial areas when compared to the standard glucose loading protocol, but this technique results in superior image quality and permits the use of smaller [18F] FDG patient doses.

Administration, Oral↗
PubMed1990

Two new two-step immunoassays for free thyroxin evaluated: solid-phase radioimmunoassay and time-resolved fluoroimmunoassay.

We measured concentrations of free thyroxin (FT4) in serum by using two new two-step FT4 assays--a solid-phase two-step radioimmunoassay. Spectria, and a time-resolved fluoroimmunoassay. Delfia--and compared the results with those by a two-step FT4 assay (RIA-gnost), a one-step FT4 analog assay (Amerlex-M), and FT4 measured after equilibrium dialysis. The new FT4 assays classified 30 hypothyroid and 43 hyperthyroid patients (untreated) well. In 138 patients with nonthyroidal illness (NTI) and in late pregnancy (n = 36), fewer subnormal FT4 values were reported by Spectria (P less than 0.001), Delfia (P less than 0.001), and RIA-gnost (P less than 0.01) than by Amerlex-M. The results of the Spectria and Delfia methods correlated with the results of the dialysis method (r = 0.76) in NTI patients and pregnancy, and were in better agreement with the clinical state than was FT4 by Amerlex-M. The FT4 values by Amerlex-M, but not by other methods, correlated with albumin concentration. We conclude that these new two-step methods present good alternatives for FT4 analysis.

Adult↗
PubMed1988

Comparative evaluation of serum thyroxine, free thyroxine and thyrotropin determinations in screening of thyroid function.

We assessed a highly sensitive immunoradiometric thyrotropin (TSH) assay in screening thyroid dysfunction in 130 consecutive outpatients from a department of medicine and 224 patients from a municipal health centre. In addition to clinical examination, three routine tests were done: a thyroxine radioimmunoassay, an analogue-based free thyroxine assay and an immunoradiometric TSH assay. Triiodothyronine and the TRH test were done, if the findings were discrepant. Discrepancy existed in 24% of cases. The TSH assay had no false negative results (sensitivity 100%). Therefore TSH could screen all patients with thyroid dysfunction. Free thyroxine was the most specific assay (specificity 96%), but many subclinically or overtly hypothyroid patients would have been missed, if that assay had been used alone. We conclude that TSH(IRMA) is the best first-line measurement for thyroid dysfunction testing among outpatients. An abnormal TSH result alone is not diagnostic, but should be followed by the measurement of thyroxine or free thyroxine.

Adolescent↗
PubMedDate not supplied

Using the ID3 algorithm to find discrepant diagnoses from laboratory databases of thyroid patients.

Rare cases are a central problem when an expert system is constructed from example cases with machine learning techniques. It is difficult to make a decision support system (DSS) to cover all possible clinical cases. An inductive learning program can be used to construct an expert system for detecting cases that differ from routine cases. The ID3 algorithm and the pessimistic pruning algorithm were tested in this study: a DSS was built directly from the data of patient records. A decision tree was generated, and the cases misclassified by the decision tree as compared with the classifications of a clinician were listed on a checklist, which formed the feedback to the clinician. In clinical situations about 5-10% of functional thyroid disorders may be misclassified. At this error level, the method found over 90% of the errors with a specificity of 95%. In simple medical classification tasks this dynamic self-learning system can be used to create a DSS that can assist in the quality control of clinical decision making.

Adult↗