Overtrained horses alter their resting pulsatile growth hormone secretion.

The influence of intensified and reduced training on nocturnal growth hormone (GH) secretion and elimination dynamics was studied in young (1.5 yr) Standardbred geldings to detect potential markers indicative for early overtraining. Ten horses trained on a treadmill for 32 wk in age-, breed-, and gender-matched fixed pairs. Training was divided into four phases (4, 18, 6, and 4 wk, respectively): 1) habituation to high-speed treadmill trotting, 2) normal training, in which speed and duration of training sessions were gradually increased, 3) in this phase, the horses were divided into 2 groups: control (C) and intensified trained (IT) group. In IT, training intensity, duration, and frequency were further increased, whereas in control these remained unaltered, and 4) reduced training (RT). At the end of phases 2, 3, and 4, blood was sampled overnight every 5 min for 8 h for assessment of GH secretory dynamics using pulse detection, deconvolution analysis, and approximate entropy (ApEn). Intensified training induced overtraining (performance decreased by 19% compared with C), which was associated with an increase in concentration peaks number (3.6 vs. 2.0, respectively), a smaller peak secretion pattern with a prolonged half-life (15.2 vs. 7.3 min, respectively), and an increased ApEn (0.89 vs. 0.49, respectively). RT did not lead to full recovery for the overtrained horses. The increased irregularity of nocturnal GH pulsatility pattern is indicative of a loss of coordinated control of GH regulation. Longer phases of somatostatin withdrawal are hypothesized to be the underlying mechanism for the observed changes in GH pulsatility pattern.

Tibolone and metabolites induce prolactin production in human endometrial stromal cells in vitro: evidence for cell-specific metabolism.

In this study, we assessed the effects of tibolone and its metabolites on the production of a progesterone sensitive parameter, prolactin, in human endometrium stroma cells in vitro. In addition, the metabolism of the compounds by isolated stromal and epithelial cells was evaluated. The reference compounds, progesterone, Org 2058, and DHT all induced prolactin production. Oestradiol also slightly induced prolactin production and enhanced the response to Org 2058. Tibolone and Delta4-tibolone were similar with regard to potency to induce prolactin levels in the culture supernatant. Their potency was lower than that of Org 2058, similar to that of progesterone and higher than that of DHT. The efficacies of tibolone, Delta4-tibolone and Org 2058 were similar (approximately 200-fold induction). The estrogenic tibolone metabolites 3alpha- and 3beta-OH tibolone also significantly stimulated prolactin production. Their potency, however, was low since significance was reached only at the highest concentrations tested. The PR antagonist Org 31710 inhibited both tibolone- and Delta4-tibolone-induced prolactin production. The responses of tibolone and Delta4-tibolone were not affected by co-incubation with the androgen receptor antagonist OH-flutamide. The effect of tibolone, but not Delta4-tibolone, was antagonized approximately 50% in combination with the highest dose (1 microM) estrogen receptor antagonist, ICI 164384. The induction of prolactin by 3alpha- and 3beta-OH tibolone was antagonized most potently by Org 31710, but also by ICI 164384 and OH-flutamide. Tibolone is metabolized differently in epithelial and stromal cells of the human endometrium. The epithelial cells mostly produce the progestagenic/androgenic Delta4-tibolone. The stromal cells produce predominantly the 3beta-OH tibolone, and some Delta4-tibolone, but the net effect observed with regard to prolactin production is progestagenic. When the metabolites 3alpha-OH, 3beta-OH, and Delta4-tibolone were added to the cultures no conversions were observed. The HPLC analyses showed no evidence for the production of sulfated metabolites. In conclusion, the net effects on endometrial stromal cells are predominantly progestagenic. Tibolone is converted by epithelial cells into Delta4-tibolone which displays progestagenic and androgenic activities, whereas in stromal cells also the estrogenic metabolites 3alpha- and 3beta-OH tibolone are formed.

alpha-Glucosidase inhibition by miglitol in NIDDM patients.

OBJECTIVE: To determine the efficacy of the alpha-glucosidase inhibitor miglitol (BAYm 1099) regarding the starch content of food. RESEARCH DESIGN AND METHODS: Thirty-six non-insulin-dependent diabetes mellitus (NIDDM) subjects were studied in a double-blind randomized study comparing treatment with a single dosage of 100 mg miglitol or placebo and a single-blind crossover comparison of three test meals in which the carbohydrate contained either 30, 50, or 70% starch, and quantities of fat and protein were kept constant. RESULTS: Postprandial blood glucose excursions were reduced by approximately 50% with miglitol after all test meals. In contrast, after miglitol treatment, maximum postprandial serum C-peptide and insulin values reached the same levels as after placebo treatment, although the time to reach these maximum levels was delayed. Free fatty acid values decreased after both miglitol and placebo similarly. Twenty-eight untoward events in 15 patients were reported in the miglitol treatment group and 11 events in 7 patients in the placebo treatment group. CONCLUSIONS: Miglitol reduces postprandial blood glucose excursions independent of the starch content of the meal. Because no effects were found on incremental postprandial maximal levels of serum insulin and C-peptide, it may be that miglitol exerts, in addition to a delay of intestinal carbohydrate absorption, extraintestinal effects as well, particularly effects on disposition of glucose or anti-insulin counterregulatory factors.

Comparison of different insulin regimens in elderly patients with NIDDM.

OBJECTIVE: To compare the metabolic effects of three different frequently used regimens of insulin administration on blood glucose control and serum lipids, and the costs associated with this treatment, in subjects with NIDDM, who were poorly controlled with oral antihyperglycemic agents. RESEARCH DESIGN AND METHODS: We studied 95 elderly patients with NIDDM (age 68 +/- 9 years, BMI 26.0 +/- 4.6 kg/m2, and median time since diagnosis of diabetes 9 years [range 1-37]; 37 men, 58 women), who were poorly controlled, despite diet and maximal doses of oral antihyperglycemic agents. Three insulin administration regimens were compared during a 6-month period: patients were randomized for treatment with a two-injection scheme (regimen A) or a combination of glibenclamide with one injection of NPH insulin, administered either at bedtime (regimen B) or before breakfast (regimen C), and insulin treatment was mainly instituted in an outpatient setting. RESULTS: After 6 months of insulin treatment, fasting blood glucose of the total patient population had decreased from an average of 14.1 +/- 2.2 to 8.3 +/- 2.0 mmol/L (P < 0.001), and HbA1c fell from 11.0 +/- 1.3 to 8.3 +/- 1.2% (P < 0.001); 34 patients reached HbA1c levels below 8.0%, 25 of them even below 7.5%. With two insulin injections daily, HbA1c decreased from 11.2 +/- 1.3 to 8.2 +/- 1.2%, while during combined treatment, HbA1c fell from 10.5 +/- 1.2 to 8.1 +/- 1.1% (regimen B) and from 11.1 +/- 1.3 to 8.5 +/- 1.1% (regimen C). Comparable improvement of the other measures of glycemic control, lipids and lipoproteins, was observed in the different treatment regimens. Body weight increase was moderate (mean +/- 4.0 kg) and similar in all patient groups. One-third of patients starting with one insulin injection daily needed a second injection to control glycemia. One episode of severe hypoglycemia was observed. Combined insulin-sulfonylurea treatment was almost 20% more expensive than twice-daily administration of insulin alone. CONCLUSIONS: Insulin treatment can safely be instituted in elderly patients with NIDDM. However, it is difficult to obtain optimal glycemic control. Insulin has moderate beneficial effects on serum lipoproteins. Although on the basis of glycemic control and weight gain, no preference for any treatment regimen can be discerned, twice-daily insulin administration is the most simple and cost-effective regimen.

Factors contributing to alterations in skeletal muscle and plasma amino acid profiles in patients with chronic obstructive pulmonary disease.

BACKGROUND: There is increasing evidence of abnormal protein metabolism in patients with chronic obstructive pulmonary disease (COPD), as reflected by lower plasma branched-chain amino acid (BCAA) concentrations and different muscle amino acid (AA) patterns than in age-matched control subjects. OBJECTIVE: We examined whether the low plasma BCAA concentrations in COPD reflect an imbalance between anabolic and catabolic processes as evidenced by a low fat-free mass (FFM) and alterations in the anabolic hormone insulin and whether discrepancies in muscle AA concentrations between studies are related to different patient characteristics. DESIGN: AA profiles in arterial plasma and quadriceps femoris muscle and insulin concentrations in venous plasma were analyzed in 28 postabsorptive COPD patients (14 with and 14 without macroscopic emphysema) and in 28 control subjects. FFM was measured by dual-energy X-ray absorptiometry. RESULTS: The lower sum of plasma BCAAs in the COPD group than in the control subjects was the result of a lower leucine concentration (P: < 0.001); no significant difference in valine and isoleucine was found between the groups. In the COPD group, the lower leucine concentrations were associated with low FFM (P: < 0.01). Compared with the control group, the muscle-to-plasma leucine gradient was higher in the COPD group (P: < 0.001) and was associated with a higher insulin concentration (P: < 0.01). Several muscle AA concentrations were higher or tended to be higher in the group without emphysema than in the control group, whereas nearly all AA concentrations were lower in the group with emphysema. CONCLUSIONS: Leucine metabolism is altered in COPD patients and is associated with low FFM and high insulin concentrations. There were striking differences in the skeletal muscle AA profile between the COPD subtypes.

Bone metabolism in galactosemia.

Classical galactosemia is an autosomal recessively inherited disorder of galactose metabolism. Treatment consists of life-long dietary restriction of galactose. Despite treatment, long-term complications occur such as a decreased bone mineral density (BMD). A decreased BMD might be the result of either dietary deficiencies secondary to the galactose-restricted diet or unknown intrinsic factors. In this study, 40 children with classical galactosemia (13 males and 27 females, aged 3-17 years) on dietary treatment were included to gain insight in the bone metabolism of galactosemics. We found weight and height Z scores significantly decreased in galactosemics. Mean areal BMD Z scores of lumbar spine and of femoral neck as measured by Dual energy X-ray Absorptiometry (DXA) were -0.6 (P < 0.001) and -0.3 (P = 0.066), respectively. Mean volumetric BMD of the femoral neck was significant lower in galactosemics (P < 0.001). The recommended dietary allowances (RDA) for calcium, magnesium, zinc, vitamin D, and protein were met in all patients. Mean serum levels of calcium, phosphate, magnesium, zinc, 1,25-dihydroxy vitamin D (1,25OHD), parathormone (PTH), 17-beta estradiol, bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were normal. Serum levels of IGF-1 Z score, carboxylated osteocalcin (cOC), N-terminal telopeptide (NTX), and C-terminal telopeptide (CTX) were significantly lower in galactosemics than in control subjects. The different bone markers were strongly correlated. The low levels of IGF-1 Z score, formation marker cOC, and resorption markers NTX and CTX suggest a decreased bone metabolism in galactosemics.

Neuron-specific enolase in cerebrospinal fluid of patients with metastatic and non-metastatic neurological disease.

Neuron-specific enolase (NSE) activities were measured in cerebrospinal fluid (CSF) in 361 patients with various neurological diseases. CSF was collected as part of the diagnostic procedure both in the control group, which consisted of 189 subjects with low back pain, and in the patient group (172 patients). The mean CSF NSE level in 189 control subjects was 7.14 +/- 1.94 micrograms/l. Slight elevations of CSF NSE (> or = 11.0 micrograms/l) were observed in 9 patients with non-malignant diseases and in 2 patients with malignant diseases. The findings of this study indicate that measurement of NSE in CSF cannot be used as an adjunctive diagnostic test for CNS metastases.

Dissociable hormonal, cognitive and mood responses to neuroendocrine challenge: evidence for receptor-specific serotonergic dysregulation in depressed mood.

Fifteen patients with major depression, dysthymia, or anxiety disorder with depressed mood (DSM-IV diagnoses) and 16 controls received single oral doses of 0.5mg/kg metachlorophenylpiperazine (m-CPP), a 5-HT(2C) agonist, and 10 mg ipsapirone, a 5-HT(1A) agonist, according to double-blind, placebo-controlled, cross-over design. The groups' levels of cortisol, adrenocorticotrophic hormone (ACTH) and prolactin did not differ at baseline. Both 5-HT agonists significantly elevated cortisol, ACTH, and prolactin. The cortisol response to ipsapirone was significantly blunted in major depression and dysthymia patients. Neuroendocrine responses to m-CPP did not differ between groups, but m-CPP selectively increased profile of mood states (POMS) depression and tenseness scores in patients. No effects of ipsapirone on mood were found. However, ipsapirone impaired memory performance in controls, but tended to improve memory performance in patients. The results support the evidence for both hypothalamic and possibly hippocampal 5-HT(1A) receptor desensitisation and non-hypothalamic, 5-HT(2C) receptor sensitisation, probably fronto-cortical, in patients with major depression and dysthymia.

Effect of strenuous exercise on fibrinogen and fibrinolysis in healthy elderly men and women.

The elevated incidence of thrombotic disease in elderly people may be associated with an increase in PAI-1 and fibrinogen with ageing. Cross-sectional studies report an inverse relation of PAI-1 and fibrinogen with physical activity, but training studies show inconsistent results. In a controlled intervention study among elderly subjects (aged 60-80 years) we observed a moderate decrease in PAI-1 antigen (4%, -2.1 +/- 2.4 ng/ml), a significant increase in t-PA activity (11%, 0.07 +/- 0.04 IU/ml) and an unexpected significant increase in fibrinogen (6%, 0.18 +/- 0.07 g/l) in subjects following a 6-month intensive training program as compared to controls. Reduction in PAI-1 antigen was significantly associated with a decrease in triglycerides (beta = 10.3 ng/ml per 1 mM, p <0.01) and insulin (beta = 2.37 ng/ml per 1 mU/l, p = 0.07). Increase in fibrinogen coincided with a rise in C-reactive protein (p <0.001). These data suggest that regular intensive activity may increase fibrinolytic activity in a moderate way, but also may cause chronically elevated plasma levels of acute phase proteins in elderly persons.

Thyroid function, depressed mood, and cognitive performance in older individuals: the Maastricht Aging Study.

The hypothesis was tested that thyroid function, as indicated by serum thyroid-stimulating hormone (TSH) level, is associated with cognitive performance in a healthy aging population. In a random sample of 120 participants recruited from the Maastricht Aging Study (MAAS), aged between 49 and 71 years, we assessed TSH level, mood state (Symptom Check List, subscale depression), and three domains of cognitive function: verbal memory, general sensorimotor speed, and complex flexibility. After correction for age, sex, and educational level, a negative association between TSH and memory function was apparent: higher levels of TSH predicted lower levels of memory performance. Exclusion of individuals with TSH levels suspect for thyroid disorder (n=2) or who were on thyroid replacement (n=3) attenuated this association. Furthermore, additional control for mood status reduced the association below the significance level. No interaction between age and TSH on cognition was found, which indicated that the TSH-memory association was independent of age group level. We conclude that the association between TSH level and memory performance was small and dependent on mood status and the presence of (possible) thyroid disease in this relatively healthy population based sample. Prospective studies are needed to address the role of thyroid function in age-related cognitive decline.

Maternal volume homeostasis in early pregnancy in relation to fetal growth restriction.

OBJECTIVE: To test the hypothesis that volume adaptation in pregnancies complicated by fetal growth restriction (FGR) is already abnormal very early in pregnancy. METHODS: In six pregnancies later complicated by FGR, volume homeostasis in the first 8 weeks was compared to that in ten normal pregnancies. Creatinine clearance, volume-dependent hormones, hemodilution-related variables, and ultrasonic cardiovascular dimensions were measured weekly between weeks 5 and 10, in the second and third trimesters, and postpartum. Differences between the two groups were analyzed by nonparametric tests. RESULTS: Very early in pregnancy, pregnancies complicated by FGR differed from normal pregnancies in the following ways: smaller left atrial diameter, smaller collapsible part of the inferior vena cava, lower serum sodium concentration, and smaller fall in serum creatinine and urea. CONCLUSION: Fetal growth restriction is preceded by defective volume adaptation very early in pregnancy. It appears that the maternal compensation mechanisms are unable to resolve the transient state of vascular underfill seen in this period in normal gestation.

Early endometriosis invades the extracellular matrix.

OBJECTIVES: To investigate whether the aminoterminal propeptides of type III procollagen are increased in patients with early endometriosis and to demonstrate that the subtle lesion of endometriosis is an active stage of the disease. DESIGN: Aminoterminal propeptide of type III procollagen was determined in serum and peritoneal fluid (PF) of 100 consecutive patients undergoing laparoscopy. SETTING: Academisch Ziekenhuis Maastricht, The Netherlands, a tertiary care center. RESULTS: Aminoterminal propeptide PF levels were significantly higher in women with early lesions of endometriosis compared with levels in two groups of controls, i.e., fertile, cycling, women without the disease (P = 0.019) and women on oral contraceptives without the disease (P = 0.036). No difference was found in aminoterminal propeptide PF levels when comparing patients with early lesions of endometriosis and patients with unexplained infertility, the third control group. Aminoterminal propeptide PF levels of patients with endometriosis without early lesions were not different from PF levels in controls. CONCLUSION: The early lesion is an active stage of endometriosis, invading the extracellular matrix. In women with unexplained infertility active, microscopic endometriosis may be present.

Occult abortion: not a major cause of infertility.

OBJECTIVES: To determine whether occult abortion is a frequent cause of infertility. DESIGN: Prospective observational clinical study. SETTING: Hospital based infertility clinic, serving as the only primary infertility care facility to a population of 250,000 people. PATIENTS: 102 subsequent infertility patients. INTERVENTIONS: Ultrasound ovulation detection, timed hCG determinations. MAIN OUTCOME MEASURE: Proportion of patients with serum hCG levels > 2.0 mIU/mL (> 2.0 IU/L) on days 12 or 13 after ultrasound-proven ovulation with subsequent appearance of the menstrual period before or at postovulation day 14. RESULTS: In 18 of 102 patients increased hCG was found. All these patients became clinically pregnant (9 spontaneous abortions, 9 ongoing pregnancies). No occult abortion occurred (95% confidence interval 0-4%). CONCLUSIONS: Occult abortion is not a frequent cause of infertility in an unselected population.

Effect of ritodrine on thyroid hormone concentrations.

In a clinical study of 17 pregnant women treated with ritodrine, a beta-2-sympathomimetic agent used for tocolysis, thyroid hormone status was assessed longitudinally. This was done in order to verify the hypothesis that an increase in T3 levels could result from adrenergic stimulation, since propanolol, a beta blocking agent, has proved to decrease T3 levels in man. We have observed a significant increase in serum T3 concentrations 24-48 h after the start of the ritodrine treatment. The changes were only temporarely since one week after the start the serum T3 concentrations did not differ significantly from the pre-treatment levels. A decrease in T3 levels was found after discontinuation of treatment. No significant changes were found in T4 and TSH concentrations excluding an influence in ritodrine therapy on the pituitary-thyroid axes. It was concluded that stimulation of type I deiodinase was responsible for the changes in T3. These beta-2-mimetic variations may explain, to a certain degree, the unwanted chronotropic cardiac side effects of ritodrine and necessitates much care in using this therapy in hyperthyroidic patients.

Prognostic factors for successful insulin therapy in subjects with type 2 diabetes.

OBJECTIVE: To assess which factors influence or predict the efficacy of insulin therapy in subjects with type 2 diabetes, who were poorly controlled despite maximal doses of oral glucose lowering agents. RESEARCH DESIGN AND METHODS: Seventy-five patients with type 2 diabetes participated (mean age (+/- SD), 67 +/- 8 years; body mass index, 25.8 +/- 5.0 kg/m2; median time since diagnosis of diabetes, 8 years (range 1-36); 27 males and 48 females). They were transferred to insulin therapy, in which case either insulin alone, or a combination of insulin and glibenclamide was employed. The importance of baseline parameters (glycaemic control, beta-cell function, measures of insulin resistance) was assessed by comparing good and poor responders (defined as achieved HbA1c < 8.0 or > 9.0%) to insulin therapy, and by multiple logistic regression analysis of these baseline parameters and achieved metabolic control. RESULTS: During insulin therapy, HbA1c levels decreased from 10.9 +/- 1.3 to 8.2 +/- 1.1% (p < 0.001), and fasting blood glucose levels decreased from 14.0 +/- 2.3 to 8.2 +/- 2.1 mmol/l (p < 0.001). Thirty patients reached HbA1c levels < 8.0%, 21 of them even < 7.5%. The mean increase in body weight was 4.5 kg. HbA1c after 6 months was 7.0 +/- 0.6% in the good responders, and 9.8 +/- 0.6% in the poor responders (p < 0.001), despite a comparable insulin dose. Baseline metabolic control was similar in both groups. Also, glucagon-stimulated and calculated insulin secretion, as well as parameters of insulin resistance, such as fasting serum insulin levels, free fatty acids, and serum triglycerides, were not different between both groups, and certainly not higher in the poor responders. Also previous metformin use was not different. However, poor responders were more obese than good responders, and had significantly longer known duration of diabetes. Multiple logistic regression confirmed that only duration of diabetes and body mass index were independent predictors of response to insulin therapy. CONCLUSIONS: We conclude that in elderly patients with type 2 diabetes improvement of glycaemic control can be achieved at the expense of some weight gain. Measurement of residual insulin secretion prior to institution of insulin treatment does not discriminate between good and poor responders to this model of therapy. Especially in obese patients with longer duration of diabetes more attention is needed in order to achieve optimal glycaemic control. Combination of insulin with newer drugs, like thiazolidinediones, may perhaps achieve this.

Clinical experience with Sandostatin LAR in patients with acromegaly.

Patients with acromegaly, who are not cured after transsphenoidal adenomectomy, may be treated with external irradiation and/or octreotide injections. Recently, a long-acting formulation of octreotide (Sandostatin LAR has become available in clinical practice. We assessed the effects of treatment with this long-acting octreotide in 18 consecutive patients with acromegaly treated in our center, who had persistent signs and symptoms of acromegaly despite transsphenoidal surgery with (n=7) or without irradiation (n=11). Twelve had already been treated with regular Sandostatin for a period of 0.5-8 years in dosages of 3 x 50 to 3 x 300 mcg s.c. (median daily dose 300 mcg). All patients started with i.m. injections of 20 mg Sandostatin LAR every 4 weeks. In the patients who started treatment with octreotide for the first time, mean serum IGF-1 levels (measured by IRMA, Nichols Diagnostics) decreased from 634+/-229 to 255+/-88 ng/ml after 3 months, 271+/-81 ng/ml after 1 year and 263+/-97 ng/ml after 2 years (all P<0.05), while random GH levels (DELFIA, Wallac) decreased from 6.6 (range 3.1-67.0) to 2.1 (0.5-3.1) mU/l after 2 years (P<0.05). In the 12 patients who had already been treated with octreotide, mean IGF-1 also fell, from 367+/-193 to 331+/-195 ng/ml (P=0.023) after 3 months, to 342+/-191 ng/ml after 1 year and 277+/-169 ng/ml (P=0.002) after 2 years, while random GH levels decreased from 4.5 (1.1-46) mU/l at baseline to 2.1 (0.4-23.0) after 2 years (P=0.003). Therefore, the average decrease of IGF-1 was 10% after 3 months and 25% after 2 years. One patient had a decrease of less than 5% (but her IGF-1 was normal, 193 ng/ml), and one patient showed no response to both regular and long-acting Sandostatin (ave. IGF-1, 755 ng/ml). No specific side-effects occurred. One patient chose to return to t.i.d. injection of regular octreotide because of slight worsening of her complaints of headache despite normal IGF-1 levels. All other patients favoured continuation of the monthly injections. In six patients, the dose had to be increased to 30-40 mg monthly because the IGF-1 levels still remained elevated. Sandostatin LAR may be considered a great improvement for the treatment of patients with (symptomatic) acromegaly.

Effect of miglitol (BAY m-1099) on fasting blood glucose in type 2 diabetes mellitus.

BACKGROUND: In type 2 diabetes mellitus, fasting blood glucose values are increased due to increased glycogenolysis and gluconeogenesis. As miglitol (BAY m-1099), an absorbable alpha-glucosidase inhibitor, can inhibit glycogenolysis, we investigated whether 200 mg miglitol ingested at bedtime could decrease fasting blood glucose values. METHODS: Twelve type 2 diabetic patients participated in a double-blind, randomised, placebo-controlled, cross-over study. The study duration was 6 weeks: 2 weeks run-in, 2 test periods of 1 week with 2 weeks of wash-out in between. During run-in and wash-out periods placebo tablets were used. Fasting blood glucose (FBG), insulin (FIRI), C-peptide (FCP), glucagon (FG), pyruvate and alanine were measured at the start of the study, at the end of the run-in and wash-out periods, and at the 6th and 7th day of each test period. RESULTS: Both during miglitol and placebo no effects on FBG (12.2 +/- 2.5 vs. 12.2 +/- 2.5 mmol/l), FIRI (80 +/- 34 vs. 82 +/- 35 pmol/l), FCP (1110 +/- 303 vs. 1043 +/- 304 pmol/l), FG (20 +/- 13 vs. 20 +/- 10 pmol/l), pyruvate (101 +/- 28 vs. 112 +/- 30 mumol/l) or alanine (440 +/- 87 vs. 465 +/- 133 mumol/l) were observed. CONCLUSIONS: Miglitol 200 mg taken at bedtime for 1 week has no influence on hepatic glucose production.

Glucagon-stimulated insulin secretion in patients with type 2 diabetes mellitus: support for the concept of glucose toxicity.

Parameters of blood glucose control and insulin secretion were evaluated in 114 patients with type 2 diabetes mellitus, who were no longer controlled satisfactorily by maximal doses of oral hypoglycaemic agents, and compared with those obtained in 11 healthy control subjects, 32 patients with recently-diagnosed type 2 diabetes, and 16 tablet-treated and 36 insulin-treated patients. Newly-diagnosed patients were slightly younger (60 +/- 13 yr) and had a slightly higher body mass index (29.4 +/- 6.5 kg/m2). Known duration of diabetes was 9 yr (range 1-37) in secondary failure, and 11 yr (range 1-31) in insulin-treated patients. Fasting blood glucose was the highest (13.8 +/- 2.8 mmol/l) in secondary failure and newly-diagnosed patients (12.6 +/- 3.8 mmol/l) compared to tablet-treated (8.7 +/- 3.3 mmol/l) and insulin-treated patients (9.6 +/- 3.2 mmol/l, p less than 0.05). HbA1c levels were comparably elevated. In insulin-treated patients, fasting plasma C-peptide levels were lower relative to the mutually comparable levels in the other 3 diabetic groups. Fasting plasma insulin levels did not differ between the 4 diabetic groups. C-peptide release after glucagon (C-peptide AUC) was comparable in all 4 diabetic groups, although in tablet-treated patients the ratio C-peptide AUC/fasting blood glucose was higher (p less than 0.05). We conclude that the clinical usefulness of determining residual insulin secretion in type 2 diabetic patients is limited, and that the similar reduction of insulin secretion in severely hyperglycaemic newly-diagnosed and secondary failure type 2 diabetic patients supports the concept of "glucose toxicity".

Changes in thyroid status in pregnant women treated with ritodrine.

In a clinical study of 17 pregnant women treated with ritodrine, a beta 2-sympathomimetic agent used for tocolysis, thyroid hormone status was assessed longitudinally. This was done in order to verify the hypothesis that an increase in T3 levels could result from adrenergic stimulation, since propranolol, a beta blocking agent, has proved to decrease T3 levels in man. Indeed, a statistically significant increase in T3 serum concentration and in T3/T4 ratio was found on the second day after the start of treatment with ritodrine (p less than 0.02 and less than 0.01 respectively). After discontinuation of treatment a decrease in T3 serum levels, compared to both treatment and pretreatment levels, was observed. The free T4 concentration showed a significant drop after the first week of treatment (p less than 0.01), but no changes were found in T4 and TSH levels. It was concluded that the beta 2-mimetic-mediated changes in thyroid status provide one more reason for restriction of the use of beta-mimetic drugs in hyperthyroidic patients and might offer an additional explanation for the undesirable chronotropic cardiac side-effects of the therapy.

Lumbar bone mineral density in adolescent female runners.

BACKGROUND: The purpose of this study was to determine if there were significant differences in lumbar bone mineral density (L2-L4, g/cm2) or several hormones among 3 groups of adolescent females: 10 amenorrheic runners, 10 eumenorrheic runners, and 10 eumenorrheic controls. EXPERIMENTAL DESIGN: comparative. SETTING: Cooper Clinic, Aerobics Center, Dallas, Texas. PATIENTS OR PARTICIPANTS: The subjects were white, non-smokers, aged 15.1-18.8 years, who were not taking birth control pills. All amenorrheic runners had less than 5 menstrual period in the past year, averaging 2,4 periods. The runners averaged approximately 36 miles/week (58.1 km) during the last 9 months of their training season and had been running for 1-5 years. INTERVENTIONS: None. MEASURES: Lumbar bone mineral density (BMD), 10 hormones, percentage of body fat, and dietary intake were measured. RESULTS: Mean lumbar BMD (g/cm2) did not differ significantly among groups (amenorrheic runners = 1.134, eumenorrheic runners = 1.165, controls = 1.148). However, expected trends were observed. Compared to the controls, the amenorrheic runners tended to have lower lumbar BMD and the eumenorrheic runners, higher. Although there were significant differences in concentrations of five serum hormones measured, all mean hormonal values were within normal ranges. Calcium intakes were low for all groups. CONCLUSIONS: In this study, with its small number of subjects and great variability within each group, it was concluded that there is no significant difference among amenorrheic runners, eumenorrheic runners, and controls in lumbar BMD. However, a longer period of amenorrhea might result in significantly lower BMD for the amenorrheic runners.