Hypercortisolism in Newly Diagnosed Type 2 Diabetes: A Prospective Study of 384 Newly Diagnosed Patients.

Cross-sectional studies in small and selected populations report a high prevalence of hypercortisolism in patients with type 2 diabetes (T2D), which could have therapeutic implications, if confirmed. We therefore estimated the prevalence of hypercortisolism in a large and unselected cohort of recently diagnosed T2D patients. Consecutive patients with recently diagnosed T2D first underwent an overnight dexamethasone (1 mg) suppression test (OD). Patients not suppressing serum cortisol ≤50 nmol/l proceeded with a 48-h low dose dexamethasone suppression test (LDDST) and 24-h urinary free cortisol collection (UFC). Patients with elevated cortisol levels according to LDDST and/or UFC underwent imaging guided by plasma ACTH levels, and assessment of bone mineral density. A total of 384 T2D patients (232male/152 females) with a mean age of 60±10 years were included. Eighty-five (22%) patients suppressed incompletely to OD of whom 20 (5%) failed to suppress after LDDST and/or had elevated UFC (=hypercortisolism). Patients with hypercortisolism did not differ as regards age, BMI, HbA1c, T-score or blood pressure, but a higher proportion of them received antihypertensive treatment (100% vs. 64%, p=0.001). Imaging revealed adrenal adenoma(s) in 9 cases and a pituitary macroadenoma in 1 case. We found a 5% prevalence of hypercortisolism in unselected, recently diagnosed T2D, which was not associated with a persuasive cushingoid phenotype. The clinical implications are therefore uncertain.

Low positive predictive value of midnight salivary cortisol measurement to detect hypercortisolism in type 2 diabetes.

BACKGROUND: Hypercortisolism is prevalent in type 2 diabetes (T2D), but analytical and functional uncertainties prevail. Measurement of salivary cortisol is considered an expedient screening method for hypercortisolism, but its usefulness in the context of T2D is uncertain. AIM: To compare late-night salivary cortisol (LNSC) with the 1 mg overnight dexamethasone suppression test (DST), which was considered 'reference standard', in T2D. PATIENTS AND METHODS: A total of 382 unselected and recently diagnosed patients with T2D underwent assessment of LNSC and DST, and the test outcome was related to age, gender, body mass index (BMI) and haemoglobin A1c levels. We used the following cut-off values: LNSC ≤ 3·6 nmol/l and DST ≤ 50 nmol/l. RESULTS: The median (range) levels of LNSC and DST were 6·1 (0·3-46·2) nmol/l and 34 (11-547) nmol/l, respectively. Hypercortisolism was present in 86% based on LNSC values and 22% based on DST. LNSC, as compared to DST, had the following test characteristics: sensitivity: 85% (95% CI: 7-92%), specificity: 14% (95% CI: 10-19%), positive predictive value: 22% (95% CI: 17-27%), negative predictive value: 76% (95% CI: 63-87%), and overall accuracy: 30% (95% CI: 25-34%). LNSC and DST values were not associated with haemoglobin A1c, BMI and age in this cohort of patients with T2D. CONCLUSION: The LNSC is characterized by very low specificity and poor positive predictive value as compared to the DST, resulting in an overall low accuracy. Further methodological and clinical studies are needed to substantiate the relevance of cortisol status in T2D.

[Tardive akathisia after long-term metoclopramide treatment].

This case report describes a 57-year-old male with symptoms of tardive akathisia after long-term metoclopramide treatment. As metoclopramide is a dopamine receptor antagonist, it has the potential to cause drug-induced movement disorders, including akathisia, which is characterised by an inner restlessness resulting in a need for constant movement. Tardive akathisia, in contrast to acute akathisia, evolves after prolonged exposure to the triggering medication and can be a permanent condition. Treatment duration of metoclopramide should be restricted, and awareness of neurological side effects is important.

Epidemiology of Cushing's syndrome.

Overt Cushing's syndrome is a rare disorder with an annual incidence of 2-3/million of which benign adrenal adenomas account for 0.6/million. The female:male ratio is 3:1. Preliminary data indicate a high proportion of subclinical Cushing's syndrome in certain risk populations such as patients with type 2 diabetes or osteoporosis. The clinical implications of these observations are presently unclear. Surgery remains first line treatment for overt disease and initial cure or remission is obtained in 65-85% of patients with Cushing's disease. Late recurrences, however, occur in up to 20% and the risk does not seem to plateau even after 20 years of follow-up. A 2- to 3-fold increase in mortality is observed in most studies, and this excess mortality seems confined to patients in whom initial cure was not obtained. Cushing's syndrome continues to pose diagnostic and therapeutic challenges and life-long follow-up is mandatory.

Comparison of the characteristics of fungal and plant tyrosinases.

Enzymatic crosslinking provides valuable means for modifying functionality and structural properties of different polymers. Tyrosinases catalyze the hydroxylation of various monophenols to the corresponding o-diphenols, and the subsequent oxidation of o-diphenols to the corresponding quinones, which are highly reactive and can further undergo non-enzymatic reactions to produce mixed melanins and heterogeneous polymers. Tyrosinases are also capable of oxidizing protein- and peptide-bound tyrosyl residues, resulting in the formation of inter- and intra-molecular crosslinks. Tyrosinases from apple (AT), potato (PT), the white rot fungus Pycnoporus sanguineus (PsT), the filamentous fungus Trichoderma reesei (TrT) and the edible mushroom Agaricus bisporus (AbT) were compared for their biochemical characteristics. The enzymes showed different features in terms of substrate specificity, stereo-specificity, inhibition, and ability to crosslink the model protein, alpha-casein. All enzymes were found to produce identical semiquinone radicals from the substrates as analyzed by electron spin resonance spectroscopy. The result suggests similar reaction mechanism between the tyrosinases. PsT enzyme had the highest monophenolase/diphenolase ratio for the oxidation of monophenolic L-tyrosine and diphenolic L-dopa, although the tyrosinases generally had noticeably lower activity on monophenols than on di- or triphenols. The activity of AT and PT on tyrosine was particularly low, which largely explains the poor crosslinking ability of the model protein alpha-casein by these enzymes. AbT oxidized peptide-bound tyrosine, but was not able to crosslink alpha-casein. Conversely, the activity of PsT on model peptides was relatively low, although the enzyme could crosslink alpha-casein. In the reaction conditions studied, TrT showed the best ability to crosslink alpha-casein. TrT also had the highest activity on most of the tested monophenols, and showed noticeable short lag periods prior to the oxidation.

Cushing's syndrome and pregnancy outcomes: a systematic review of published cases.

Pregnancy in Cushing's syndrome (CS) is extremely rare due to the influence of hypercortisolism on the reproductive axis. Purpose of this study is to investigate whether the etiology of CS in pregnancy determines a different impact on the fetal/newborn and maternal outcomes. We performed a systematic review of cases published in the literature from January 1952 to April 2015 including the words "Cushing AND pregnancy". We included 168 manuscripts containing 220 patients and 263 pregnancies with active CS during pregnancy and with a history of CS but treated and cured hypercortisolism at the time of gestation. Adrenal adenoma was the main cause of active CS during pregnancy (44.1 %). Women with active CS had more gestational diabetes mellitus (36.9 vs. 2.3 %, p = 0.003), gestational hypertension (40.5 vs. 2.3 %, p < 0.001) and preeclampsia (26.3 vs. 2.3 %, p = 0.001) than those with cured disease. The proportion of fetal loss in active CS was higher than in cured CS (23.6 vs. 8.5 %, p = 0.021), as well as global fetal morbidity (33.3 vs. 4.9 %, p < 0.001). The predictors of fetal loss in active CS were etiology of hypercortisolism [Odds Ratio -OR-for pregnancy-induced CS 4.7 (95 % Confidence Interval-CI 1.16-18.96), p = 0.03], publication period [OR for "1975-1994" 0.10 (95 % CI 0.03-0.40), p = 0.001] and treatment during gestation (p = 0.037, [OR medical treatment 0.25 (95 % CI 0.06-1.02), p = 0.052], [OR surgical treatment 0.34 (95 % CI 0.11-1.06), p = 0.063]). The period of diagnosis of CS (before, during or after pregnancy) was the only predictor of overall fetal morbimortality [OR for diagnosis during pregnancy 4.66 (95 % CI 1.37-15.83), p = 0.014]. Patients with active CS, especially in pregnancy-induced CS, experienced more problems in pregnancy and had the worst fetal prognosis in comparison to other causes. Diagnosis of CS during pregnancy was also associated with worse overall fetal morbimortality. Both medical treatment and surgery during pregnancy appeared to be protective in avoiding fetal loss.

DIAGNOSIS OF ENDOCRINE DISEASE: Prevalence of hypercortisolism in type 2 diabetes patients: a systematic review and meta-analysis.

OBJECTIVE: Type 2 diabetes (T2D) and Cushing's syndrome (CS) share clinical characteristics, and several small studies have recorded a high prevalence of hypercortisolism in T2D, which could have therapeutic implications. We aimed to assess the prevalence of endogenous hypercortisolism in T2D patients. DESIGN: Systematic review and meta-analysis of the literature. METHODS: A search was performed in SCOPUS, MEDLINE, and EMBASE for original articles assessing the prevalence of endogenous hypercortisolism and CS in T2D. Data were pooled in a random-effect logistic regression model and reported with 95% confidence intervals (95% CI). RESULTS: Fourteen articles were included, with a total of 2827 T2D patients. The pooled prevalence of hypercortisolism and CS was 3.4% (95% CI: 1.5-5.9) and 1.4% (95 CI: 0.4-2.9) respectively. The prevalence did not differ between studies of unselected patients and patients selected based on the presence of metabolic features such as obesity or poor glycemic control (P = 0.41 from meta-regression). Imaging in patients with hypercortisolism (n = 102) revealed adrenal tumors and pituitary tumors in 52 and 14% respectively. CONCLUSIONS: Endogenous hypercortisolism is a relatively frequent finding in T2D, which may have therapeutic implications.

Laccase-catalyzed polymerization of tyrosine-containing peptides.

Laccase-catalyzed polymerization of tyrosine and tyrosine-containing peptides was studied in the presence and absence of ferulic acid (FA). Advanced spectroscopic methods such as MALDI-TOF MS, EPR, FTIR microscopy and HPLC-fluorescence, as well as more conventional analytical tools: oxygen consumption measurements and SDS/PAGE were used in the reaction mechanism studies. Laccase was found to oxidize tyrosine and tyrosine-containing peptides, with consequent polymerization of the compounds. The covalent linkage connecting the compounds was found to be an ether bond. Only small amounts of dityrosine bonds were detected in the polymers. When FA was added to the reaction mixtures, it was found to be incorporated into the polymer structure. Thus, in addition to homopolymers, different heteropolymers containing two or four FA residues were formed in the reactions.

Aldehyde-induced xanthine oxidase activity in raw milk.

In the present study, the aldehyde-induced pro-oxidative activity of xanthine oxidase was followed in an accelerated raw milk system using spin-trap electron spin resonance (ESR) spectroscopy. The aldehydes acetaldehyde, propanal, hexanal, trans-2-hexenal, trans-2-heptenal, trans-2-nonenal, and 3-methyl-2-butenal were all found to initiate radical reactions when added to milk. Formation of superoxide through aldehyde-induced xanthine oxidase activity is suggested as the initial reaction, as all tested aldehydes were shown to trigger superoxide formation in an ultrahigh temperature (UHT) milk model system with added xanthine oxidase. It was found that addition of aldehydes to milk initially increased the ascorbyl radical concentration with a subsequent decay due to ascorbate depletion, which renders the formation of superoxide in milk with added aldehyde. The present study shows for the first time potential acceleration of oxidative events in milk through aldehyde-induced xanthine oxidase activity.

Chicken model for studying dietary antioxidants reveals that apple (Cox's Orange)/broccoli (Brassica oleracea L. var. italica) stabilizes erythrocytes and reduces oxidation of insoluble muscle proteins and lipids in cooked liver.

A chicken model for studying the effects of antioxidants in the diet on oxidative status was set up. Chickens fed a semi-synthetic diet low in antioxidants showed a remarkable decrease in erythrocyte stability toward H(2)O(2) or 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), but increases in catalase activity in liver, carbonyls in insoluble muscle proteins, and enhanced lipid oxidation in heat-treated liver samples compared to that of conventionally fed chickens. Thus, this chicken model proved to be more susceptible to oxidative changes than conventionally fed chickens, reflecting a low antioxidative defense. Supplementing this low antioxidant diet with 10% apple/broccoli mixture counteracted these changes, except for activity of catalase in the liver and AAPH-induced lysis of erythrocytes. Supplementation with 10% sweet corn only reduced the carbonyl content in insoluble proteins. However, neither low antioxidant diet nor vegetable supplements affected selected antioxidative enzymes or oxidative stability of lipids in heat-treated muscle tissue.

Significance of preslaughter stress and different tissue PUFA levels on the oxidative status and stability of porcine muscle and meat.

Polyunsaturated fatty acids (PUFAs) and exercise-induced stress are known to increase the oxidative susceptibility of lipids in muscle tissue. In contrast, antioxidative enzymes, e.g., catalase, superoxide dismutase, and glutathione peroxidase, are known to help sustain the delicate oxidative balance in biological tissue upon the application of stressors. The present study investigates the combined effect of different diet-induced muscle PUFA contents and preslaughter stress on the activity of antioxidative muscle enzymes and the oxidative stability of cooked meat. An increased content of unsaturated fatty acids in the tissue led to a decreased activity of lactate dehydrogenase in the plasma, indicating increased cell integrity. Catalase activity in the muscle tissue increased with increasing PUFA levels. However, this upregulation in antioxidative status of the muscle could not counteract the subsequent development of accelerated lipid oxidation in cooked meat as measured in terms of thiobarbituric acid reactive substances. Moreover, preslaughter stress induced increasing oxidative changes with elevated PUFA levels in the muscle tissue.

[Acromegaly masked by symptomatic hyperprolactinaemia]. / Akromegali maskeret af symptomatisk hyperprolaktinæmi.

A 48-year-old woman presented with galactorrhoea, moderate hyperprolactinaemia (0.97 IU/l) and a pituitary macroadenoma (10 × 7 × 6 mm). Over a period of six years the patient had developed overt acromegalic features and was subsequently diagnosed with acromegaly while treated with dopamine receptor agonist. Acromegaly should always be considered in patients presenting with hyperprolactinaemia and a pituitary adenoma.

[Dopamin agonist treatment and fibrotic heart valve disease in hyperprolactinaemia patients]. / Behandling med dopaminagonister og udvikling af hjerteklapsygdom hos patienter med hyperprolaktinæmi.

Treatment with dopamin agonists, particularly cabergoline, is the primary and preferred therapy for prolactinomas and symptomatic hyperprolactinaemia due to its effectiveness and tolerability. However, an association has been demonstrated between fibrotic heart valve disease and high-dose dopamin agonist use in patients with Parkinson's disease in several echocardiographic studies. Such observations have prompted a number of studies of valvular function in cabergoline-treated hyperprolactinaemia patients. These studies have failed to show an increased prevalence of clinically significant valvular regurgitation.

The Danish Centre for Strategic Research in Type 2 Diabetes (DD2) study: implementation of a nationwide patient enrollment system.

This paper aims to describe the patient enrollment system and implementation strategy for the new nationwide Danish Centre for Strategic Research in Type 2 Diabetes (DD2) project. The paper will also describe the design, current content, and pilot testing of the DD2 registration form. The challenge of the DD2 project was to construct a registration system functioning in the entire Danish health care system, where new type 2 diabetes patients are initially met, and with the capacity to enroll 200 newly diagnosed diabetes patients per week nationwide. This requires a fast and simple registration that is part of everyday clinical practice in hospital outpatient clinics and general practitioner (GP) clinics. The enrollment system is thus built on a tested, rational design where patients need only one visit and only specific limited data about physical activity, anthropometric measures, and family history of diabetes are collected during a brief patient interview. Later, supplemental data will be extracted by computerized linkage with existing databases. The feasibility of this strategy was verified in a pilot study. For maximum flexibility, three different ways to fill in the DD2 registration form were provided and an interactive webpage was constructed. The DD2 project also involves collection of blood and urine samples from each diabetes patient, to be stored in a biobank. Clinicians may obtain the samples themselves or refer patients to the nearest clinical biochemical department. GPs have the additional option of referring patients to the nearest hospital outpatient diabetes clinic to obtain interview data, clinical data, and samples. At present, the enrollment system is in use at 17 hospital outpatient diabetes clinics and 45 GP clinics nationwide, together enrolling 40 new type 2 diabetes patients per week in the DD2 project. A total of 990 patients have now been enrolled and the DD2 is ready to expand nationwide.

The Danish Centre for Strategic Research in Type 2 Diabetes (DD2) Project: rationale and planned nationwide studies of genetic predictors, physical exercise, and individualized pharmacological treatment.

Here we provide an overview of the rationale and methods of a series of planned population based studies within the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) Project. The project aims to support and evaluate ongoing political and administrative efforts to implement nationwide guidelines for maintaining metabolic control in newly diagnosed type 2 diabetes (T2D) patients to prevent diabetic complications and improve quality of life. The DD2 is designed as a prospective cohort study (collection of epidemiological data) supplemented by randomized clinical intervention trials (on physical exercise and individualized pharmacological treatment) and the establishment of a biobank comprised of material from a large number of newly diagnosed T2D patients. Inclusion of the majority of newly diagnosed T2D patients as they are diagnosed at their general practitioner or diabetes hospital outpatient clinics and entered into the DD2 cohort will establish a nationwide database comprising a large number of future incident cases of T2D in Denmark. These cases will form the project cohort of the DD2. Within the first 6 months of diagnosis, all patients will be invited to contribute to a biobank of DNA, plasma, urine, and tissue sampling. The DNA biobank will enable future studies of the effect of pharmacological treatment and outcome in subsets of patients with specific genetic risk profiles covering disease etiology and specific drug kinetics and metabolism. We will also perform two clinical intervention trials examining: the effectiveness of physical exercise on diabetes-related outcomes and the impact of trial outcomes on individualized pharmacological treatment. Moreover, the DD2 will serve as a platform for testing and developing new antidiabetic drugs. All together, we expect this study to contribute to substantially improved diabetes care in T2D patients locally and abroad.

Heart valve disease among patients with hyperprolactinemia: a nationwide population-based cohort study.

BACKGROUND: Increased risk of heart valve disease during treatment with certain dopamine agonists, such as cabergoline, has been observed in patients with Parkinson's disease. The same compound is used to treat hyperprolactinemia, but it is unknown whether this also associates with heart valve disease. OBJECTIVES: The objective of the study was to assess the incidence of diagnosed heart valve disease and cardiac valve surgery among patients with hyperprolactinemia, compared with a general population cohort in Denmark. DESIGN: This was a nationwide, population-based, cohort study based on a nationwide hospital registry. METHODS: We identified 2381 hyperprolactinemia patients with a first-time diagnosis recorded from 1994 through 2010 in the registry, with no previous hospital diagnosis of heart valve disease. Each patient was compared with 10 age- and gender-matched comparison cohort members from the general population. The association between hyperprolactinemia and heart valve disease was analyzed with Cox's proportional hazards regression, controlling for potential confounding factors. To assess the risk of cardiac valve surgery and avoid ascertainment bias, a subanalysis was made in a cohort of 2,387 hyperprolactinemia patients with no previous cardiac valve surgery and 23,870 comparison cohort members. RESULTS: Nineteen hyperprolactinemic patients (0.80%) were diagnosed with heart valve disease during a total of 17,759.8 yr of follow-up, compared with 75 persons (0.31%) in the comparison cohort during 179,940.6 yr of follow-up [adjusted hazard ratio 2.27 (95% confidence interval 1.35-3.82)]. Seven of the 10 patients treated with cabergoline and diagnosed with heart valve disease were asymptomatic and diagnosed on the basis of an echocardiography performed as a safety measure. However, only two patients with hyperprolactinemia (0.08%) underwent surgery, compared with 28 persons in the general population cohort (0.12%) [adjusted hazard ratio 0.55 (95% confidence interval 0.13-2.42)]. CONCLUSIONS: Data from the present register-based study do not support that hyperprolactinemia or its treatment is associated with an increased risk of clinically significant heart valve disease.

Targeting amyloid-beta by glucagon-like peptide -1 (GLP-1) in Alzheimer's disease and diabetes.

INTRODUCTION: Epidemiological evidence suggests an association between type 2 diabetes (T2DM) and Alzheimer's disease (AD), in that one disease increases the risk of the other. T2DM and AD share several molecular processes which underlie the tissue degeneration in either disease. Disturbances in insulin signaling may be the link between the two conditions. Drugs originally developed for T2DM are currently being considered as possible novel agents in the treatment of AD. AREAS COVERED: This review discusses the potential role of glucagon-like peptide -1 (GLP-1) treatment in AD. GLP-1 receptors are expressed in areas of the brain important to memory and learning, and GLP-1 has growth-factor-like properties similar to insulin. A key neuropathological feature of AD is the accumulation of amyloid-beta (Aß). In preclinical studies, GLP-1 and longer lasting analogues have been shown to have both neuroprotective and neurotrophic effects, and to protect synaptic activity in the brain from Aß toxicity. EXPERT OPINION: A convincing amount of evidence has shown a beneficial effect of GLP-1 agonist treatment on cognitive function, memory and learning in experimental models of AD. GLP-1 analogues may therefore be the new therapeutic agent of choice for intervention in AD.

Modifications of amino acids during ferulic acid-mediated, laccase-catalysed cross-linking of peptides.

Mass spectral analysis demonstrated oligomerization of peptides that had been subjected to oxidation catalysed by Trametes (Coriolus) versicolor laccase. Peptide oligomerization occurred only when cysteines or tyrosines were present in the peptides. MS/MS confirmed the cross-linking in tyrosine-containing peptides to be located between tyrosine residues. Ferulic acid mediated oligomerization of cysteine-containing peptides, but prevented cross-linking of tyrosines when used in the same concentration as the peptides. This suggests an antioxidative effect of ferulic acid in relation to tyrosine oxidation, although incorporation of ferulic acid into peptide oligomers was found in some of the tyrosine-containing peptides. No other modifications to amino acid residues by laccase-catalysed oxidation were observed by mass spectroscopy. Thus, it is suggested that oxidative modifications of other amino acids observed in proteins oxidized by laccase are not major reaction products of laccase-catalysed oxidation.

Cross-linking proteins by laccase-catalyzed oxidation: importance relative to other modifications.

Laccase-catalyzed oxidation was able to induce intermolecular cross-links in beta-lactoglobulin, and ferulic acid-mediated laccase-catalyzed oxidation was able to induce intermolecular cross-links in alpha-casein, whereas transglutaminase cross-linked only alpha-casein. In addition, different patterns of laccase-induced oxidative modifications were detected, including dityrosine formation, formation of fluorescent tryptophan oxidation products, and carbonyls derived from histidine, tryptophan, and methionine. Laccase-catalyzed oxidation as well as transglutaminase induced only minor changes in surface tension of the proteins, and the changes could not be correlated to protein cross-linking. The presence of ferulic acid was found to influence the effect of laccase, allowing laccase to form irreducible intermolecular cross-links in beta-lactoglobulin and resulting in proteins exercising higher surface tensions due to cross-linking as well as other oxidative modifications. The outcome of using ferulic acid-mediated laccase-catalyzed oxidation to modify the functional properties of proteinaceous food components or other biosystems is expected to be highly dependent on the protein composition, resulting in different changes of the functional properties.

Myocellular triacylglycerol breakdown in females but not in males during exercise.

The resting content and use of myocellular triacylglycerol (MCTG) during 90 min of submaximal exercise [60% of peak oxygen uptake (VO(2 peak))] were studied in 21 eumenorrheic female and 21 male subjects at different training levels [untrained (UT), moderately trained (MT), and endurance trained (END)]. Males and females were matched according to their VO(2 peak) expressed relative to lean body mass, physical activity level, and training history. All subjects ingested the same controlled diet for 8 days, and all females were tested in the midfollicular phase of the menstrual cycle. Resting MCTG, measured with the muscle biopsy technique, averaged 48.4 +/- 4.2, 48.5 +/- 8.4, and 52.2 +/- 5.8 mmol/kg dry wt in UT, MT, and END females, respectively, and 34.1 +/- 4.9, 31.6 +/- 3.3, and 38.4 +/- 3.0 mmol/kg dry wt in UT, MT, and END males, respectively (P < 0.001, females vs. males in all groups). Exercise decreased MCTG content in the female subjects by an average of 25%, regardless of training status, whereas in the male groups MCTG content was unaffected by exercise. The arterial plasma insulin concentration was higher (P < 0.05) and the arterial plasma epinephrine concentration was lower (P < 0.05) in the females than in the males at rest and during exercise. MCTG use was correlated to the resting concentration of MCTG (P < 0.001). We conclude that resting content and use of MCTG during exercise are related to gender and furthermore are independent of training status.