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P Seppälä

Publications and source records attributed to P Seppälä.

At least 19 recordsLinked to original sources

Effect of obesity on the response to insulin therapy in noninsulin-dependent diabetes mellitus.

An initial improvement in glycemic control is often followed by gradual deterioration of glycemia during insulin treatment of patients with noninsulin-dependent diabetes mellitus (NIDDM). We examined the causes of such worsening in a 12-month follow-up analysis of 100 insulin-treated NIDDM patients in the Finnish Multicenter Insulin Therapy Study who were treated with either combination therapy with insulin or insulin alone. In the entire study group, glycemic control averaged 9.7 +/- 0.2% at 0 months and 8.0 +/- 0.1%, 8.0 +/- 0.1%, 8.2 +/- 0.1%, and 8.5 +/- 0.2% at 3, 6, 9, and 12 months (P < 0.001 for each time point vs. 0 months). Glycemic control at 12 months was significantly worse than that at 3 (P < 0.001), 6 (P < 0.001), and 9 months (P < 0.02). Baseline body mass index was the most significant predictor of deterioration in glycemic control. During 1 yr, hemoglobin A1c decreased almost 3-fold more (by 1.7 +/- 0.2%; P < 0.001 vs. 0 months) in patients whose baseline weight was below the mean baseline body mass index of 28.1 kg/m2 (nonobese patients) than in those whose weight exceeded 28.1 kg/m2 (obese patients; 0.5 +/- 0.2%; P = NS vs. 0 months; P < 0.01 vs. obese patients). Glycemic control improved similarly over 1 yr in the nonobese subjects and deteriorated similarly in the obese patients regardless of their treatment regimen. Insulin doses, per body weight, were similar in the nonobese and obese patients. The nonobese patients consistently gained less weight during 12 months of combination therapy with insulin (3.5 +/- 0.6 kg at 12 months) than during insulin therapy alone (5.1 +/- 0.6 kg; P < 0.05). The treatment regimen did not influence weight gain in the obese group, who gained 4.4 +/- 1.0 kg during combination therapy with insulin and 4.5 +/- 1.1 kg during insulin therapy alone. We reached the following conclusions: 1) after an initial good response, glycemic control deteriorates more in obese than in nonobese patients with NIDDM; 2) in obese patients, weight gain per se cannot explain the poor glycemic response to combination or insulin therapy, but it may induce a disproportionately large increase in insulin requirements because of greater insulin resistance in the obese than in the nonobese; 3) in nonobese patients, glycemic control improves equally during 1 yr with combination therapy with insulin and insulin alone, but combination therapy with insulin is associated with less weight gain than treatment with insulin alone; 4) weight gain appears harmful, as it is associated with increases in blood pressure and low density lipoprotein cholesterol.

Adult↗

Effect of insulin treatment on serum lipoprotein(a) in non-insulin-dependent diabetes.

In order to evaluate whether Lp(a), a lipoprotein that is potentially thrombogenic and atherogenic, is a potential risk factor for CAD in non-insulin-dependent diabetes (NIDDM), we compared the Lp(a) and its distribution in 145 NIDDM patients with that in 94 healthy control subjects. Furthermore, we studied the effect of insulin treatment on serum Lp(a) in 108 patients with NIDDM. Male and female NIDDM patients had similar Lp(a) concentrations to healthy controls (median value 167 mg L-1, range 15-1550 mg L-1 vs. 157 mg L-1, range 15-919 mg L-1, NS and 92, range 15-1190 mg L-1 vs. 103 mg L-1, range 15-842 mg L-1, NS). Also, the cumulative distribution of Lp(a) did not differ between the NIDDM patients and healthy subjects. Insulin treatment increased Lp(a) in diabetics with a Lp(a) concentration of less than 300 mg L-1, but this effect was not related to the concomitant improvement in metabolic control (mean change (+/- SEM) of HbA1c from 9.80 +/- 0.15 to 8.00 +/- 0.12; P < 0.001). In subjects with elevated Lp(a) concentrations (> 300 mg L-1) the Lp(a) concentration was unaffected by insulin, despite a similar improvement in glycaemic control. These results suggest that insulin may modulate the concentration of Lp(a).

Adult↗

Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: Insulin is widely used to improve metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), but there is no consensus about the optimal regimen of insulin treatment. METHODS: We treated 153 patients with NIDDM for three months with five regimens: (1) oral hypoglycemic drug therapy plus NPH insulin given at 7 a.m. (the morning-NPH group), (2) oral hypoglycemic drug therapy plus NPH insulin given at 9 p.m. (the evening-NPH group), (3) NPH and regular insulin (ratio, 70 units to 30 units) given before breakfast and dinner (the two-insulin-injection group), (4) NPH insulin at 9 p.m. and regular insulin before meals (the multiple-insulin-injection group), and (5) continued oral hypoglycemic drug therapy (the control group). RESULTS: The mean (+/- SE) value for glycosylated hemoglobin decreased similarly in all four insulin-treatment groups (1.7 +/- 0.3, 1.9 +/- 0.2, 1.8 +/- 0.3, and 1.6 +/- 0.3 percent, respectively). The decrease was significantly greater in these four groups than in the control group (0.5 +/- 0.2 percent; P < 0.001 vs. all insulin-treated groups). Weight gain was significantly less (1.2 +/- 0.5 kg) in the evening-NPH group than in the other insulin-treatment groups (2.2 +/- 0.5 kg in the morning-NPH group, 1.8 +/- 0.5 kg in the two-insulin-injection group, and 2.9 +/- 0.5 kg in the multiple-injection group; P < 0.05). In addition, the increment in the mean diurnal serum free insulin concentration was 50 to 65 percent smaller in the evening-NPH group than in the other insulin-treatment groups. Subjective well-being improved significantly more in the insulin-treatment groups than in the control group (P < 0.001). CONCLUSIONS: In patients with NIDDM who are receiving oral hypoglycemic drug therapy, the addition of NPH insulin in the evening improves glycemic control in a manner similar to combination therapy with NPH insulin in the morning, a two-insulin-injection regimen, or a multiple-insulin-injection regimen, but induces less weight gain and hyperinsulinemia. The data thus suggest that patients with NIDDM do not benefit from multiple insulin injections and that nocturnal insulin administration appears preferable to daytime administration.

Administration, Oral↗

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↗

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↗

Endocrine abnormalities in patients with adrenal tumours incidentally discovered on computed tomography.

To determine endocrine activity of adrenal tumours incidentally discovered on C.T., we examined 20 consecutive patients. They underwent thorough hormonal assessment and scintigraphic scanning with radioactive cholesterol under dexamethasone suppression (19 patients). Biochemical findings compatible with cortisol hypersecretion were detected in 5 patients. One patient had reduced reserves of cortisol secretion and one had hyporeninemic hypoaldosteronism. The scintigraphy showed no uptake in 10, unilateral uptake in 4, and bilateral uptake in 5 patients. In 3 patients the finding was unilateral on CT. but bilateral on scintigraphy. Signs of autonomous cortisol production were more common among patients who had uptake on scintigraphy. At the operation of 8 patients only benign lesions were found. During the follow-up (9 to 49 months) of the 12 unoperated patients, the tumour disappeared in one and remained unchanged in the others. No changes occurred in the biochemical findings except in one patient whose cortisol response to 1 mg of dexamethasone became abnormal. Since slight hypercortisolism or a bilateral disease often exists behind an incidentally discovered adrenal tumour, we emphasize the importance of careful assessment of cortisol metabolism and a scintigraphic scanning under dexamethasone suppression in the examination of these patients.

17-Ketosteroids↗

Unusual association of hyperkalemia and hypertension.

We report an unusual association of hyperkalemia, mild hyperchloremic acidosis, and hypertension in a young woman. Pseudohyperkalemia, Addison's disease, renal insufficiency, classical hyporeninemic hypoaldosteronism, isolated hypoaldosteronism, and iatrogenic causes were excluded. The patient's findings were compatible with a rare syndrome designated as type II pseudohypoaldosteronism, Gordon's syndrome.

Adult↗

Plasma and urinary C-peptide in the classification of adult diabetics.

Plasma and urinary C-peptide determinations in the discrimination between insulin-requiring and non-insulin-requiring diabetes were elevated in 61 adult diabetics. Specimens for C-peptide determinations were taken on two consecutive days: on the first day plasma C-peptide concentrations were determined before and 6 min after intravenous glucagon administration. On the second day 2- and 4-h urinary C-peptide excretion was measured after an individual breakfast. Results of urinary C-peptide analyses were expressed as molar concentration and also as molar quantity excreted (without any corrections and related to creatinine excretion). Glucagon-stimulated plasma C-peptide turned out to be a reliable criterion for the detection of insulin requirement. Sixty-nine per cent of diabetics included in this study were classifiable by basal plasma C-peptide concentrations. Two-hour postprandial urinary C-peptide/creatinine quotient turned out to be slightly less sensitive (89%) than the glucagon test (94%) and of equal specificity (96%). Glucagon-stimulated plasma C-peptide and postprandial urinary C-peptide excretion correlated significantly among insulin-requiring diabetics (r = 0.73), but not among non-insulin-requiring diabetics (r = 0.23). We regard determination of stimulated plasma C-peptide as a primary investigation for the direct assessment of endogenous insulin secretory reserves for clinical management decisions. Determination of postprandial urinary C-peptide is applicable in selected situations for non-invasive assessment of insulin secretion.

Adolescent↗

Effect of guar gum on glipizide absorption in man.

The effect of 4.75 g guar gum, a fibre preparation, on the absorption of 2.5 mg glipizide has been studied in 10 healthy volunteers given a standard breakfast. Three different experimental protocols were used: glipizide without guar gum (Treatment 1), glipizide with guar gum (Treatment 2) and guar gum 30 min after the drug together with breakfast (Treatment 3). The serum glipizide at 30 minutes was higher during Treatment 2 than Treatment 3 (p less than 0.01), but neither differed from the control treatment. The AUCs for glipizide were calculated up to 8 hours. They did not differ significantly between the treatment, although there was a non-significant trend to lower values during Treatment 3. Serum insulin and blood glucose levels were determined up to 3 h. Corresponding to differences in the glipizide concentration, serum insulin was highest and blood glucose lowest at 30 minutes during Treatment 2. According to this single dose study, guar gum does not have any substantial deleterious effect on the absorption of glipizide. The lack of effect may be due to the complete gastrointestinal absorption of glipizide.

Adult↗

Virilization during pregnancy due to bilateral hyperthecosis. A case report.

A case of recurrent maternal virilization associated with bilateral hyperthecosis of the ovary during two pregnancies is described. In the first pregnancy, serum testosterone increased to the level of 12.5 nmol/l and in the second pregnancy to 35 nmol/l and after delivery to 66 nmol/l.5 months after the second birth the testosterone level was 2.7 nmol/l and virilization had spontaneously regressed. Puerperal stimulation tests with human menopausal or with human chorionic gonadotropin did not increase ovarian androgen production. Female babies were not virilized.

Adult↗

C-peptide determination in the choice of treatment in diabetes mellitus.

The predictive value of the intravenous glucagon test in assessing the requirement of insulin therapy in diabetes mellitus was evaluated in 105 adult diabetics. Basal and stimulated C-peptide concentrations and increments of C-peptide concentration were examined separately among newly and previously diagnosed diabetics. The poststimulatory C-peptide concentration of 0.6 nmol/l (Novo, antibody M 1230) proved to be the most reliable basis for the choice of therapy. Adequate therapy could have been assessed in 70 cases (67%) without glucagon stimulation. To derive maximal information of plasma C-peptide concentrations, a biphasic scheme of the use for C-peptide determinations and glucagon stimulation is presented. Basal and stimulated C-peptide levels of insulin-requiring diabetics correlated negatively with the duration of diabetes but they did not correlate with the relative body weights. Basal and stimulated C-peptide levels of non-insulin-requiring diabetics did not correlate with the duration of diabetes, but they correlated positively with the relative body weights.

Adolescent↗

Remissions in newly diagnosed type 1 (insulin-dependent) diabetes: influence of interferon as an adjunct to insulin therapy.

We studied the effect of interferon as an adjunct to conventional insulin therapy on the early course of Type 1 diabetes in 43 newly diagnosed patients. Compared with conventional therapy, interferon administration slightly delayed the improvement of glucose homeostasis and the rise of high density lipoprotein cholesterol, while C-peptide secretion was unaffected. Independent of the type of therapy, 18 patients (42%) entered partial remission. The remission began 2.0 +/- 0.6 months (mean +/- SEM) from the start of therapy and lasted for 4.1 +/- 1.1 months. Seven patients (16%) were still in remission 1 year after diagnosis. The patients who entered remission had higher initial C-peptide secretion, lower glycosylated haemoglobin levels and better initial control than patients without remission. Thus, interferon provided no benefits as an adjunct to conventional insulin therapy in unselected patients with newly diagnosed Type 1 diabetes. An important factor for the development of remission was the presence of C-peptide secretion at the time of diagnosis.

Adolescent↗