Biomedical subjects

A Edo Meinders

Publications and source records attributed to A Edo Meinders.

At least 19 recordsLinked to original sources

PubMed2006

Sustained beneficial metabolic effects 18 months after a 30-day very low calorie diet in severely obese, insulin-treated patients with type 2 diabetes.

Eighteen insulin-treated obese type 2 diabetic patients were followed for 18 months after they followed a 30-day very low calorie diet (VLCD, 450kCal/day) with the cessation of all glucose-lowering medication. After the 30-day VLCD, caloric intake was slowly increased to eucaloric and glucose-lowering medication was restarted if necessary. On day 0 and 30 of the VLCD and after 18 months follow-up, bodyweight, blood-pressure, glycaemic control and lipid levels were measured. The 30-day VLCD significantly reduced bodyweight (-11.7+/-0.7kg, mean+/-S.E.M.) and improved dyslipidaemia, hypertension and glycaemia. As a group, this effect was sustained at 18 months follow-up despite the fact that patients used less lipid-, blood-pressure- and glucose-lowering medication. Especially, the use of insulin was significantly reduced: 18 out of 18 patients on day 0 (mean 137+/-22units/day); 5 out of 18 patients at 18 months (86+/-14units/day). Patients using insulin at 18 months had regained weight to prediet levels, but still had a better cardiovascular risk profile compared with before the dietary intervention. Thus, a once-only 30-day VLCD leads to a sustained improvement in glycaemia, dyslipidaemia and blood-pressure up to 18 months follow-up in obese type 2 diabetic patients, even, although to a lesser extent, in patients who regained body-weight.

Blood Glucose↗

PubMed2006

Activation of dopamine D2 receptors simultaneously ameliorates various metabolic features of obese women.

The metabolic syndrome comprises a cluster of metabolic anomalies including insulin resistance, abdominal obesity, dyslipidemia, and hypertension. Previous studies suggest that impaired dopamine D2 receptor (D2R) signaling is involved in its pathogenesis. We studied the acute effects of bromocriptine (a D2R agonist) on energy metabolism in obese women; body weight and caloric intake remained constant. Eighteen healthy, obese women (BMI 33.2 +/- 0.6 kg/m(2), mean age 37.5 +/- 1.7, range 22-51 yr) were studied twice in the follicular phase of their menstrual cycle in a prospective, single-blind, crossover design. Subjects received both placebo (P; always first occasion) and bromocriptine (B; always second occasion) on separate occasions for 8 days. At each occasion blood glucose and insulin were assessed every 10 min for 24 h, and circadian plasma free fatty acid (FFA) and triglyceride (TG) levels were measured hourly. Fuel oxidation was determined by indirect calorimetry. Body weight and composition were not affected by the drug. Mean 24-h blood glucose (P < 0.01) and insulin (P < 0.01) were significantly reduced by bromocriptine, whereas mean 24 h FFA levels were increased (P < 0.01), suggesting that lipolysis was stimulated. Bromocriptine increased oxygen consumption (P = 0.03) and resting energy expenditure (by 50 kcal/day, P = 0.03). Systolic blood pressure was significantly reduced by bromocriptine. Thus these results imply that short-term bromocriptine treatment ameliorates various components of the metabolic syndrome while it shifts energy balance away from lipogenesis in obese humans.

Adult↗

PubMed2006

Activation of dopamine D2 receptors lowers circadian leptin concentrations in obese women.

CONTEXT: Leptin release is regulated by factors other than fat mass alone. Previous observations provide indirect evidence for an inhibitory effect of dopaminergic neurotransmission on leptin secretion. This study was done to establish the effect of bromocriptine treatment on circadian plasma leptin concentrations in obese humans. OBJECTIVE: The objective of the study was to study the acute effects of bromocriptine (a D2R agonist) on circadian leptin levels in obese women, whereas body weight and caloric intake remained constant. DESIGN: This was a prospective, single-blind, crossover study (2004). SETTING: The study was conducted at a clinical research center. PARTICIPANTS: Eighteen healthy obese women (body mass index 33.2 +/- 0.6 kg/m(2)) were studied twice in the early follicular phase of their menstrual cycle. INTERVENTION(S): Treatment consisted of bromocriptine or placebo for 8 d. MAIN OUTCOME MEASURE(S): Blood was collected during 24 h at 20-min intervals for determination of leptin concentrations at the last day of medical treatment (bromocriptine or placebo). Mean 24-h serum concentrations were determined for insulin, glucose, free fatty acids, and triglycerides. RESULTS: Short-term treatment with bromocriptine reduced leptin concentration (placebo 33.6 +/- 2.5 vs. bromocriptine 30.5 +/- 2.5 ng/liter, P = 0.03). Free fatty acid concentrations were increased by treatment with bromocriptine. The increase of free fatty acids was inversely related with the decline of leptin levels. The decline of glucose, insulin, or prolactin concentrations in response to bromocriptine was not correlated with the reduction of leptin. CONCLUSION: Activation of dopamine D2 receptors by bromocriptine lowers circulating leptin levels in obese women, which suggests that dopaminergic neurotransmission is involved in the control of leptin release in humans.

Adult↗

PubMed2006

The relation between leptin and insulin remains when insulin secretion is disturbed.

BACKGROUND: Serum insulin and leptin levels correlate positively. It is not known whether this relation remains the same in cases of severely disturbed insulin secretion and after rapid weight loss. We therefore studied the relation between insulin and leptin in obese type 2 diabetic patients before and after considerable weight loss. METHODS: In 17 obese type 2 diabetic patients, blood glucose-lowering medication was discontinued (day-1) and a 30-day very low calorie diet (VLCD, 450 kcal/day) was started. On days 0, 2, and 30, body weight, body fat mass [with bioelectrical impedance analysis (BIA)], fasting serum glucose, insulin, and leptin were determined. Homeostatic model assessment was used to estimate insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta). On days 2 and 30, an intravenous glucose tolerance test (IVGTT) was performed. RESULTS: Fasting serum leptin levels correlated positively with fasting serum insulin levels (r=0.72, p=0.001 on day 2; r=0.78, p=0.001 on day 30) and area under the curve (AUC) of insulin (r=0.74, p=0.001 on day 2; r=0.84, p=0.0001 on day 30), as well as HOMA-beta, as a measure of insulin secretion, even after correction for body mass index (BMI) and body fat mass, with which leptin was also positively correlated. CONCLUSION: In a group of obese type 2 diabetic patients with a wide range of residual endogenous insulin secretion, we found a positive relation between fasting serum leptin and insulin levels, even after correction for BMI and body fat mass. This was true both before weight loss and during energy restriction with weight loss.

Journal Article↗

PubMed2006

The effect of prednisolone on serum sodium concentration.

BACKGROUND: Glucocorticoids are widely used in clinical practice. In addition to their anti-inflammatory effects, they influence the salt and water homeostasis. Although parts of the latter action have been studied individually, there are no reports in stable outpatients on the net effect of glucocorticoids on serum sodium concentration. METHODS: A group of 23 patients on chronic prednisolone therapy was compared with a control population with respect to serum sodium concentration. Intra-individual changes in serum sodium concentration after the initiation of prednisolone therapy were studied separately in 14 patients. RESULTS: A significantly higher serum sodium level of 1.67mmol/L (P=0.03) was observed in the prednisolone-treated patients, whereas initiation of prednisolone was accompanied by an increase of 2.61mmol/L (P=0.004). The doses and duration of prednisolone therapy had no relation to the increase in serum sodium concentration. CONCLUSION: Prednisolone therapy in stable outpatients results in a small, yet significant, increase in serum sodium concentration.

Journal Article↗

PubMed2006

Decrease in visceral fat following diet-induced weight loss in upper body compared to lower body obese premenopausal women.

BACKGROUND: Obesity is associated with numerous metabolic disturbances, such as insulin resistance, diabetes mellitus type 2, dyslipidemia, and hypertension. An excess of fat within the abdomen, so-called visceral adiposity, confers a greater and independent health risk of metabolic and cardiovascular complications than does adipose tissue accumulation elsewhere. The present study aimed to investigate a possible differential effect of diet-induced weight loss in visceral fat mass and metabolic parameters in obese individuals with the upper body (UBO) and lower body (LBO) obese phenotype. METHODS: The obese subjects were prescribed a liquid, very-low calorie diet to reduce 50% of their overweight (15% body weight loss). Specific body fat measurements (MRI, BIA), anthropometrics, and fasting metabolic parameters were obtained in control subjects and two groups of obese subjects (UBO and LBO) before and after weight loss. RESULTS: Weight loss was accompanied by significant decreases in total, subcutaneous, and visceral fat in both UBO and LBO women. The largest reduction in visceral fat mass was found in the UBO women (absolute decrease 223+/-32 cm(2) vs 122+/-91 cm(2) in LBO women; P=0.01), while the amount of visceral fat was reduced to normal levels in LBO women (155+/-25 cm(2) after weight loss vs 143+/-17 cm(2) in controls; P=NS). Furthermore, weight loss significantly lowered fasting glucose, total cholesterol, and LDL cholesterol concentrations in UBO women. CONCLUSION: The obese phenotype is preserved after body weight loss. UBO women have to lose a larger amount of overweight in order to bring the amount of fat in the visceral depot down to normal levels and to obtain normalization of their cardiovascular risk profile.

Journal Article↗

PubMed2006

Insulin-mediated phosphorylation of the proline-rich Akt substrate PRAS40 is impaired in insulin target tissues of high-fat diet-fed rats.

Clinical insulin resistance is associated with decreased activation of phosphatidylinositol 3'-kinase (PI3K) and its downstream substrate protein kinase B (PKB)/Akt. However, its physiological protein substrates remain poorly characterized. In the present study, the effect of in vivo insulin action on phosphorylation of the PKB/Akt substrate 40 (PRAS40) was examined. In rat and mice, insulin stimulated PRAS40-Thr246 phosphorylation in skeletal and cardiac muscle, the liver, and adipose tissue in vivo. Physiological hyperinsulinemia increased PRAS40-Thr246 phosphorylation in human skeletal muscle biopsies. In cultured cell lines, insulin-mediated PRAS40 phosphorylation was prevented by the PI3K inhibitors wortmannin and LY294002. Immunohistochemical and immunofluorescence studies showed that phosphorylated PRAS40 is predominantly localized to the nucleus. Finally, in rats fed a high-fat diet (HFD), phosphorylation of PRAS40 was markedly reduced compared with low-fat diet-fed animals in all tissues examined. In conclusion, the current study identifies PRAS40 as a physiological target of in vivo insulin action. Phosphorylation of PRAS40 is increased by insulin in human, rat, and mouse insulin target tissues. In rats, this response is reduced under conditions of HFD-induced insulin resistance.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Increased circadian prolactin release is blunted after body weight loss in obese premenopausal women.

We recently showed that prolactin (PRL) release is considerably enhanced in obese women in proportion to the size of their visceral fat mass. PRL release is inhibited by dopamine 2 receptor (D2R) activation, and dietary restriction/weight loss are associated with increased dopaminergic signaling in animals. Therefore, we hypothesized that enhanced PRL release in obese humans would be reversed by weight loss. To evaluate this postulate, we measured 24-h plasma PRL concentrations at 10-min intervals in 11 obese premenopausal women (BMI 33.3 +/- 0.7 kg/m2) before and after weight loss (50% reduction of overweight/15% absolute weight loss, using a very low-calorie diet) in the follicular phase of their menstrual cycle. The 24-h PRL concentration profiles were analyzed by a peak detection program (Cluster) and a wave form-independent deconvolution technique (Pulse). Spontaneous 24-h PRL secretion was significantly reduced in obese women [mean daily release, before 128 +/- 24 vs. after weight loss 110 +/- 17 microg/liter distribution volume (Vdl)(-1) x 24 h, P = 0.05]. Body weight loss particularly blunted PRL secretory burst mass (Pulse area, before 230 +/- 28 vs. after weight loss 221 +/- 31 microg/Vdl(-1) x 24 h, P = 0.03), whereas burst frequency was unaffected (no. of pulses, before 11 +/- 1 vs. after weight loss 12 +/- 1 n/24 h, P = 0.69). Thus elevated PRL secretion rate in obese women is significantly reduced after loss of 50% of overweight. We speculate that amelioration of deficit D2R-mediated neurotransmission and/or diminutions of circulating leptin/estrogen levels might be involved in the physiology of this phenomenon.

Adaptation, Physiological↗

PubMed2005

Spontaneous diurnal thyrotropin secretion is enhanced in proportion to circulating leptin in obese premenopausal women.

CONTEXT: Recent evidence implicates leptin as an important modulator of thyroid axis activity. OBJECTIVE: The objective of this study was to study spontaneous 24-h TSH secretion and 24-h circulating leptin concentrations in obese and lean women. DESIGN: This was a prospective parallel study (2004). SETTING: This study was conducted at the Clinical Research Center (Leiden University Medical Center, Leiden, The Netherlands). PARTICIPANTS: Twelve healthy obese premenopausal women (body mass index, 33.2 +/- 0.9 kg/m2) and 11 lean controls (body mass index, 21.4 +/- 0.5 kg/m2) were studied in the follicular phase of their menstrual cycle. INTERVENTION(S): There were no interventions in this study. MAIN OUTCOME MEASURE(S): Spontaneous 24-h TSH concentrations (10-min time intervals) and secretion were calculated using waveform-independent deconvolution technique (pulse). Twenty-four-hour circulating leptin concentrations (20-min time intervals) were measured. RESULTS: Mean TSH concentration (obese, 1.9 +/- 0.2 vs. lean, 1.1 +/- 0.1 mU/liter; P = 0.009) and secretion rate (obese, 43.4 +/- 5.5 vs. lean, 26.1 +/- 2.2 mU/liter distribution volume.24 h; P = 0.011) were substantially enhanced in obesity, whereas the fasting free T4 (fT4) concentrations were similar (fT4 in obese, 15.4 +/- 1.5 vs. in lean, 16.4 +/- 1.5 pmol/liter; P = 0.147). TSH secretion was positively related to 24-h leptin concentrations (r2= 0.31; P = 0.007). CONCLUSIONS: TSH release is enhanced in the face of normal plasma fT4 concentrations in obese premenopausal women, and hyperleptinemia may well be involved in this neuroendocrine alteration.

Adult↗

PubMed2005

High circulating thyrotropin levels in obese women are reduced after body weight loss induced by caloric restriction.

CONTEXT: Previous clinical studies concerning the impact of body weight loss on single plasma TSH concentration measurements or the TSH response to TRH in obese humans have shown variable results. OBJECTIVE: The objective of this study was to investigate the effect of weight loss induced by caloric restriction on diurnal TSH concentrations and secretion in obese humans. DESIGN: This was a clinical, prospective, crossover study. SETTING: The study was conducted at the Clinical Research Center of Leiden University Medical Center. PARTICIPANTS: Eleven obese premenopausal women (body mass index, 33.3 +/- 0.7 kg/m2) were studied. INTERVENTION: The study intervention was weight loss (50% reduction overweight by caloric restriction). MAIN OUTCOME MEASURE(S): Twenty-four-hour plasma TSH concentrations (10-min intervals) and the 24-h TSH secretion rate, calculated by a waveform-independent deconvolution technique (Pulse), were determined. RESULTS: The 24-h TSH secretion rate was significantly higher in obese women than in normal weight controls, and weight loss was accompanied by diminished TSH release (before weight loss, 43.4 +/- 6.4 mU/liter.24 h; after weight loss, 34.4 +/- 5.9 mU/liter.24 h; P = 0.02). Circulating free T3 levels decreased after weight loss from 4.3 +/- 0.19 to 3.8 +/- 0.14 pmol/liter (P = 0.04). Differences in 24-h TSH release correlated positively with the decline of circulating leptin (r2 = 0.62; P < 0.01). CONCLUSIONS: Elevated TSH secretion in obese women is significantly reduced by diet-induced weight loss. Among various physiological cues, leptin may be involved in this phenomenon. The decreases in TSH and free T3 may blunt energy expenditure in response to long-term calorie restriction, thereby frustrating weight loss attempts of obese individuals.

Adult↗

PubMed2005

Infectious complications of central venous catheters increase the risk of catheter-related thrombosis in hematology patients: a prospective study.

PURPOSE: We studied whether the risk of central venous catheter (CVC) -related thrombosis increased after an episode of CVC-related infection in patients undergoing intensive chemotherapy. Secondly, we determined whether thrombosis can be predicted or excluded by CVC lock fluid surveillance cultures. PATIENTS AND METHODS: In a prospective setting, 105 consecutive patients were carefully examined for CVC-related infection and thrombosis. In all patients, microbial surveillance cultures of CVC lock fluid were taken every other day. All patients with clinical suspicion of CVC-related thrombosis underwent Doppler ultrasound or additional venography. RESULTS: The cumulative incidence of CVC-related infection was 24% (25 of 105 patients). Clinically manifest thrombosis occurred in 13 (12%) of 105 patients. In patients with CVC-related infection, the risk of thrombosis increased markedly in comparison to those without infection (relative risk, 17.6; 95% CI, 4.1 to 74.1). In patients having two or more positive subsequent CVC lock fluid cultures with identical micro-organisms, 71.4% developed thrombosis, as compared with 3.3% in patients with negative or a single positive culture. CONCLUSION: The risk of clinically manifest thrombosis is increased after an episode of CVC-related infection in patients undergoing intensive chemotherapy. Surveillance culturing of CVC lock fluid may be clinically useful in estimating the risk for thrombosis and the instigation of focused early intervention.

Adolescent↗

PubMed2005

Hypophosphatemia: an update on its etiology and treatment.

Phosphate plays a key role in several biological processes. In recent years, new insights have been obtained into the regulation of the phosphate metabolism, including a growing amount of evidence suggesting that factors other than parathyroid hormone (PTH) and vitamin D are involved in maintaining the phosphate balance. A new class of phosphate-regulating factors, the so-called "phosphatonins," have been shown to be important in phosphate-wasting diseases. However, the role of the phosphatonins in the normal human homeostasis remains to be established. The incidence of hypophosphatemia in selected patient series can be more than 20%, with clinical sequelae ranging from mild to life threatening. Only when combined with phosphate depletion does hypophosphatemia become clinically significant. The factors that are involved in the phosphate homeostasis, the pathophysiology, the relevance in patient care, the clinical manifestations, and an appropriate management of phosphate depletion are discussed in this review.

Extracellular Matrix Proteins↗

PubMed2005

Two days of a very low calorie diet reduces endogenous glucose production in obese type 2 diabetic patients despite the withdrawal of blood glucose-lowering therapies including insulin.

The mechanism of the blood glucose-lowering effect of a 2-day very low calorie diet (VLCD; 1890 kJ/d) in combination with the cessation of all blood glucose-lowering agents was studied in 12 (7 women, 5 men) obese (body mass index, 36.3 +/- 1.0 kg/m 2 [mean +/- SEM]) type 2 diabetic patients (age, 55 +/- 4 years; HbA 1c , 7.3% +/- 0.4%) undergoing insulin therapy. Endogenous glucose production (EGP) and whole body glucose disposal (6,6 2 H 2 -glucose), lipolysis ( 2 H 5 -glycerol), and substrate oxidation (indirect calorimetry) rates were measured before and after the intervention in basal and hyperinsulinemic conditions. After 2 days of a VLCD and discontinuation of all blood glucose-lowering therapies, fasting plasma glucose levels did not increase (11.3 +/- 1.3 vs 10.3 +/- 1.0 mmol/L). Basal EGP significantly declined (14.2 +/- 1.0 to 11.9 +/- 0.7 mu mol/kg per minute; P = .009). Basal metabolic clearance rate of glucose and rate of basal lipolysis did not change. During hyperinsulinemia, EGP (5.5 +/- 0.8 to 5.2 +/- 0.5 mu mol/kg per minute), whole body glucose disposal (12.1 +/- 0.7 to 11.3 +/- 1.0 mu mol/kg per minute), the metabolic clearance rate of glucose, and the rate of lipolysis did not change after the 2-day intervention. Cessation of blood glucose-lowering therapy in combination with a 2-day VLCD does not lead to hyperglycemia and is associated with a reduction in basal EGP. Insulin-stimulated whole body glucose disposal did not improve, nor did insulin suppressibility of EGP and lipolysis.

Adult↗

PubMed2005

Effect of a 2-day very low-energy diet on skeletal muscle insulin sensitivity in obese type 2 diabetic patients on insulin therapy.

This study investigates the molecular mechanisms underlying the blood glucose-lowering effect of a 2-day very low-energy diet (VLED, 1883 kJ/d) in 12 obese (body mass index, 36.3 +/- 1.0 kg/m2 [mean +/- SEM]) type 2 diabetic (HbA(1C) 7.3% +/- 0.4%) patients simultaneously taken off all glucose-lowering therapy, including insulin. Endogenous glucose production (EGP) and glucose disposal ([6,6-2H2]-glucose) were measured before and after the VLED in basal and hyperinsulinemic (40 mU/m2 per minute) euglycemic conditions. Insulin signaling and expression of GLUT-4, FAT/CD36, and triglycerides were assessed in muscle biopsies, obtained before the clamp and after 30 minutes of hyperinsulinemia. Fasting plasma glucose decreased from 11.3 +/- 1.3 to 10.3 +/- 1.0 mmol/L because of a decreased basal EGP (14.2 +/- 1.0 to 11.9 +/- 0.7 micromol/kg per minute, P = .009). Insulin-stimulated glucose disposal did not change. No diet effect was found on the expression of the insulin receptor and insulin receptor substrate-1 or on phosphatidylinositol 3'-kinase activity, or on FAT/CD36 expression pattern, GLUT-4 translocation, or triglyceride distribution in either the basal or insulin-stimulated situation. Unexpectedly, basal PKB/Akt phosphorylation on T308 and S473 increased after the diet, at equal protein expression. In conclusion, a 2-day VLED lowers fasting plasma glucose via a decreased basal EGP without an effect on glucose disposal. Accordingly, no changes in activation of phosphatidylinositol 3'-kinase, triglyceride distribution, FAT/CD36 expression, and GLUT-4 translocation were found in skeletal muscle biopsies.

Blood Glucose↗

PubMed2005

The effect of statin therapy on endothelial function in type 2 diabetes without manifest cardiovascular disease.

OBJECTIVE: Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes and is preceded by endothelial dysfunction. Flow-mediated dilation (FMD) is a noninvasive technique for measuring endothelial dysfunction. We aimed to determine the effect of long-term statin therapy versus placebo on FMD in patients with type 2 diabetes without manifest CVD. RESEARCH DESIGN AND METHODS: A randomized, placebo-controlled, double-blind trial was performed with 250 type 2 diabetic patients. Patients were given 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, the 0.4 mg cerivastatin was replaced by 20 mg simvastatin, without deblinding the study. The primary end point was the change in FMD, measured by B-mode ultrasound, after 2 years. RESULTS: Determinants of baseline FMD were diabetes duration, common carotid intima-media thickness, and brachial artery diameter. FMD at baseline was 1.51% in the placebo group and 1.66% in the statin group and did not change significantly after 2 years. CONCLUSIONS: The 2-year statin therapy had no effect on FMD in type 2 diabetes. Statin-induced improvement of cardiovascular risk in patients with type 2 diabetes may be mediated through mechanisms other than increased nitric oxide availability.

Blood Flow Velocity↗

PubMed2005

No effect of statin therapy on silent myocardial ischemia in patients with type 2 diabetes without manifest cardiovascular disease.

OBJECTIVE: Coronary artery disease is the most important cause of mortality in patients with type 2 diabetes. We aimed to determine the prevalence of silent myocardial ischemia (SMI) and the effect of statin therapy on SMI in type 2 diabetic patients without manifest cardiovascular disease. RESEARCH DESIGN AND METHODS: A randomized, placebo-controlled, double-blind trial was performed in 250 patients with type 2 diabetes without manifest cardiovascular disease. Patients were given either 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, cerivastatin 0.4 mg was replaced by 20 mg simvastatin without deblinding the study. The primary end point was the change in ischemic episodes, duration, and burden as measured by 48-h ambulatory electrocardiography (AECG) over 2 years. RESULTS: At baseline, 47 of 233 (20%) evaluable ambulatory electrocardiograms showed evidence of ischemia. After 2 years, there was a trend toward more ischemia in both treatment groups, without significant differences between the changes in ischemic parameters (episodes P = 0.498; duration P = 0.697; burden P = 0.798) in the two treatment groups. Cardiovascular events occurred in 12 patients in the placebo group and in two patients in the statin group (P = 0.006). There was no relationship between these cardiovascular events and the presence of SMI at baseline. CONCLUSIONS: SMI occurred in 20% of type 2 diabetes patients without manifest cardiovascular disease. There was no effect from 2 years of statin therapy on SMI. In contrast, we observed a significantly lower cardiovascular event rate on statin therapy. AECG may not be a proper tool for risk stratification in patients with type 2 diabetes.

Awareness↗

PubMed2004

Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men.

Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. Injection of hypocretin-1 acutely suppresses TRH and TSH release in rats. In contrast, subchronic administration does not appear to affect the hypothalamo-pituitary-thyroid ensemble in animals. We explored (in 7 patients and 7 controls) whether hypocretin deficiency impacts circulating TSH levels and circadian timing of TSH release in narcoleptic humans. Plasma TSH concentration profiles (blood samples taken at 10-min intervals during 24 h) and TSH levels in response to TRH injection were analyzed by Cluster, robust regression, approximate entropy (ApEn), and deconvolution. Circulating TSH levels were lower in patients, which was primarily attributable to lower pulse amplitude and nadir concentrations. TSH secretion correlated positively with mean 24-h leptin levels (R2 = 0.46, P = 0.02) and negatively with amount of sleep (R2 = 0.29, P = 0.048). Pattern-synchrony between 24-h leptin and TSH concentrations was demonstrated by significant cross-correlation and cross-ApEn analyses with no differences between controls and patients. Sleep onset was closely associated with a fall in circulating TSH. Features of diurnal rhythmicity of circulating TSH fluctuations were similar in patients and controls, with the acrophase occurring shortly after midnight. Thyroxine and triiodothyronine concentrations were similar in patients and controls and did not display a diurnal rhythm. The response of plasma TSH levels to TRH was also similar in both groups. Sleep patterns in narcoleptics were significantly disorderly compared with controls, as measured by ApEn (P = 0.006). In summary, circulating TSH concentrations are low in hypocretin-deficient narcoleptic men, which could be attributable to their low plasma leptin levels and/or their abnormal sleep-wake cycle.

Adaptation, Physiological↗

PubMed2004

Renal contribution to increased clearance of exogenous growth hormone in obese hypertensive patients.

To evaluate the possible role of the kidney in the enhanced metabolic clearance rate (MCR) of GH in obesity, we studied the kinetics of GH and renal fractional extraction of GH (RFEGH) in 12 male hypertensive patients over a wide range of body weights (71.7-129 kg) while undergoing contrast angiography on suspicion of renal artery stenosis. A continuous infusion of recombinant human GH was administered during a continuous infusion of somatostatin to suppress endogenous GH secretion. After 2 h of GH infusion, when plasma GH had reached a steady state at concentrations that were still in the physiological range, blood was sampled from the left and right renal arteries and veins for determination of GH levels. Subsequently, the GH infusion was stopped, and GH kinetics were investigated with noncompartmental analysis. In none of the patients was hemodynamically significant renal artery stenosis present. Whole body MCR of GH averaged 375 +/- 142 ml/min. Average GH levels were significantly higher in arterial plasma than in simultaneously sampled renal venous plasma (P < 0.001). RFEGH was 8.6 +/- 6.8%. The MCRs of both GH and RFEGH correlated significantly with body weight, body fat mass, and endogenous creatinine clearance. Renal uptake of GH per 100 g kidney tissue correlated inversely with MCR. These results suggest that RFEGH rises with increasing adiposity, but per unit of renal mass, the capacity of the kidney to remove GH from the circulation falls at high MCR values.

Adipose Tissue↗