Durable biochemical response and safety with oral octreotide capsules in acromegaly.

Objective: The objective of this study is to report results from the open-label extension (OLE) of the OPTIMAL trial of oral octreotide capsules (OOC) in adults with acromegaly, evaluating the long-term durability of therapeutic response. Design: The study design is an OLE of a double-blind placebo-controlled (DPC) trial. Methods: Patients completing the 36-week DPC period on the study drug (OOC or placebo) or meeting predefined withdrawal criteria were eligible for OLE enrollment at 60 mg/day OOC dose, with the option to titrate to 40 or 80 mg/day. The OLE is ongoing; week 48 results are reported. Results: Forty patients were enrolled in the OLE, 20 each having received OOC or placebo, with 14 and 5 patients completing the DPC period as responders, respectively. Ninety percent of patients completing the DPC period on OOC and 70% of those completing on placebo completed 48 weeks of the OLE. Maintenance of response in the OLE (i.e. insulin-like growth factor I (IGF1) ≤ 1.0 × upper limit of normal (ULN)) was achieved by 92.6% of patients who responded to OOC during the DPC period. Mean IGF1 levels were maintained between the end of the DPC period (0.91 × ULN; 95% CI: 0.784, 1.045) and week 48 of the OLE (0.90 × ULN; 95% CI: 0.750, 1.044) for those completing the DPC period on OOC. OOC safety was consistent with previous findings, with no increased adverse events (AEs) associated with the higher dose and improved gastrointestinal tolerability observed over time. Conclusions: Patients with acromegaly maintained long-term biochemical response while receiving OOC, with no new AEs observed with prolonged OOC exposure.

Pharmaceutical interventions for weight-loss maintenance: no effect from cabergoline.

BACKGROUND: Weight regain is a major limitation to successful weight maintenance following weight loss. Observational studies suggest that stimulation of dopamine receptors in the central nervous system is associated with weight loss and inhibition of weight gain. Our objective was to test the hypothesis that dopamine agonist treatment would prevent weight regain following acute weight loss in individuals with obesity. METHODS: We conducted a 2-year double blind randomised controlled trial comparing the effect of a dopamine agonist, cabergoline, with placebo on weight regain in obese individuals who had lost at least 5% of their body weight using an 800 kcal/day commercial meal replacement programme. The primary outcome measure was the difference in mean weight between the treatment and control groups over the 2-year period following randomisation. RESULTS: At 24 months, there was no difference in body weight between cabergoline and placebo treatment after adjustment for age, gender and baseline values (0.6 kg (95% CI: -1.5, 2.6), p = 0.58). The mean (±SD) baseline body weight of the randomised participants was 101.8 kg, the mean (±SD) weight loss with the 800 kcal/day diet was 7.1 ± 1.8 kg and the mean (±SD) weight regain at 24 months was 5.1 ± 7.5 kg. There were no significant differences in BMI, percent weight loss, waist circumference, resting energy expenditure, blood pressure or metabolic parameters at 24 months between the two groups. CONCLUSIONS: Treatment with the dopamine agonist cabergoline does not prevent weight regain in obese individuals following weight loss.

The sensitivity and specificity of thyroglobulin concentration using repeated measures of urinary iodine excretion.

PURPOSE: Iodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine excess. Tg is considered as a sensitive index of iodine status in groups of children and adults, but its usefulness for individuals is unknown. The aim of this study was to determine the diagnostic performance of Tg as an index of iodine status in individual adults. METHODS: Adults aged 18-40 years (n = 151) provided five spot urine samples for the measurement of urinary iodine concentration expressed as µg/L (UIC), µg/g of creatinine (I:Cre), and µg/day (estimated UIE); the mean of the five samples was used as the reference standard. Participants also provided a blood sample for the determination of Tg, thyroid-stimulating hormone (TSH), and free thyroxine (FT4). RESULTS: The median of UIC, I:Cre, estimated UIE, and Tg was 72 (range 16-350) µg/L, 90 (range 33-371) µg/g, 129 (range 41-646) µg/day, and 16.4 (range 0.8-178.9) µg/L, respectively. Using Tg cut-offs of >10, >11, >13, and >15 µg/L, the sensitivity and specificity for UIC, I:Cre, and estimated UIE ranged from 52 to 79% and 20-48%, respectively, below the acceptable value of ≥80%. Furthermore, receiver-operating characteristic (ROC) curves for Tg using the three measurements of urinary iodine were situated close to the chance line and the area under the curve ranged from 0.49 to 0.52. CONCLUSIONS: The results from this cross-sectional study indicate that Tg has low sensitivity and specificity to repeated measures of urinary iodine excretion. Further studies are still needed to investigate the usefulness of Tg as a biomarker of individual iodine status.

Iodine Supplementation of Mildly Iodine-Deficient Adults Lowers Thyroglobulin: A Randomized Controlled Trial.

CONTEXT: An inverse relationship between thyroglobulin (Tg) and urinary iodine concentration (UIC) has been found in children, potentially making Tg a viable blood marker of iodine status. The application of Tg in adults is unknown. OBJECTIVE: The objective of the study was to determine the efficacy of Tg to assess iodine status in adults. DESIGN: This was a randomized, double-blind, placebo-controlled, clinical trial. SETTING: The study was conducted in Dunedin, New Zealand. PARTICIPANTS: Mildly iodine deficient adults (n = 112) aged 18­40 years participated in the study. INTERVENTION: Participants were supplemented with 150 µg of iodine as potassium iodate or placebo daily for 24 weeks. At baseline and 24 weeks, participants provided five casual urine samples for UIC determination; serum TSH and free T4 (FT4) was also measured. Tg was determined at baseline and 8, 16, and 24 weeks. MAIN OUTCOME MEASURES: A change in Tg concentration between the iodine-supplemented and placebo groups at 24 weeks. RESULTS: At baseline, the overall median UIC was 65 µg/L, confirming that participants were mildly iodine deficient (ie, median UIC between 50 and 99 µg/L). The overall median Tg was 16.6 µg/L; TSH and FT4 were within normal reference ranges. At 24 weeks, the median UIC of the placebo and supplemented groups was significantly different, 79 and 168 µg/L, respectively (P < .001). Tg in the iodine-supplemented group decreased by 12%, 20%, and 27% compared with the placebo group at 8 (P = .045), 16 (P < .001), and 24 weeks (P < .001); there were no significant changes in TSH and FT4. CONCLUSION: Improved iodine status as assessed by UIC was associated with a concomitant decrease in Tg concentration, demonstrating that Tg is a useful biomarker of iodine status in a group of adults.

Optimizing Deep Brain Stimulation of the Nucleus Accumbens in a Reward Preference Rat Model.

OBJECTIVE/HYPOTHESIS: Deep brain stimulation (DBS) has become the preferred therapy for a growing number of treatment-resistant neuropsychiatric conditions, offering the benefit of being amenable to fine-tuning to enhance its efficacy. However, while some DBS parameters are routinely adjusted, the stimulation is almost always delivered in a continuous "tonic" pattern, which may be suboptimal at times. Our overall aim is to investigate the application of differing levels of rewarding DBS to the reconditioning of behavioral "trigger" and "non-trigger" stimuli in impulse-control disorders (including addiction). As a first step, we used a rat model of nucleus accumbens (NAc) DBS to rigorously compare the relative reward values of different stimulation paradigms. We hypothesized that delivering pulses in a more physiological pattern would prove more rewarding than delivering tonic stimulation. MATERIALS AND METHODS: We implanted microelectrodes in the left NAc shell and trained rats to initiate and terminate DBS to demonstrate their "preference" between different brain stimulation reward (BSR) paradigms. We tested a range of BSR paradigms, including tonic, intermittent tonic, and burst paradigms. Two paradigms were compared at a time, and paired t-tests were used to determine whether the rats significantly "preferred" one paradigm over another. RESULTS: The rats significantly preferred intermittent tonic BSR paradigms to continuous and burst paradigms, and generally preferred paradigms that delivered more pulses over the stimulation period. CONCLUSIONS: These findings highlight that the standard approach of delivering tonic DBS is not optimal under all circumstances. Further research should investigate which DBS paradigms are best for different brain disorders.

Systemic capillary leak syndrome: a case-report.

We report a case of a patient presenting with episodic hypotension, tachycardia and oedema, with an elevated serum IgG kappa paraprotein level. She was diagnosed as having systemic capillary leak syndrome and upon commencing oral theophylline has had no further presentations. The patient has since progressed to multiple myeloma.

'Exercise snacks' before meals: a novel strategy to improve glycaemic control in individuals with insulin resistance.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether small doses of intense exercise before each main meal ('exercise snacks') would result in better blood glucose control than a single bout of prolonged, continuous, moderate-intensity exercise in individuals with insulin resistance. METHODS: Nine individuals completed three exercise interventions in randomised order. Measures were recorded across 3 days with exercise performed on the middle day, as either: (1) traditional continuous exercise (CONT), comprising 30 min moderate-intensity (60% of maximal heart rate [HRmax]) incline walking before dinner; (2) exercise snacking (ES), consisting of 6 × 1 min intense (90% HRmax) incline walking intervals 30 min before each meal; or (3) composite exercise snacking (CES), encompassing 6 × 1 min intervals alternating between walking and resistance-based exercise, 30 min before meals. Meal timing and composition were controlled within participants for exercise interventions. RESULTS: ES attenuated mean 3 h postprandial glucose concentration following breakfast (by 1.4 ± 1.5 mmol/l, p = 0.02) but not lunch (0.4 ± 1.0 mmol/l, p = 0.22), and was more effective than CONT following dinner (0.7 ± 1.5 mmol/l below CONT; p = 0.04). ES also reduced 24 h mean glucose concentration by 0.7 ± 0.6 mmol/l (p = 0.01) and this reduction persisted for the subsequent 24 h (lower by 0.6 ± 0.4 mmol/l vs CONT, relative to their baselines; p = 0.01). CES was just as effective as ES (p > 0.05 for all glycaemic variables) at improving glycaemic control. CONCLUSIONS/INTERPRETATION: Dosing exercise as brief, intense 'exercise snacks' before main meals is a time-efficient and effective approach to improve glycaemic control in individuals with insulin resistance.

Ingestion of thermally oxidized sunflower oil decreases postprandial lipemia mainly in younger individuals.

Animal studies have shown that diets rich in thermally oxidized fat increase glucose and decrease insulin and triglyceride (TG) concentrations in the blood. We hypothesized that ingestion of a potato meal rich in thermally oxidized sunflower oil (TOSO) would decrease postprandial concentrations of insulin, incretins, and TG and increase plasma glucose concentrations. Twenty healthy subjects aged 22 to 70 years consumed meals rich in TOSO or unheated sunflower oil and containing paracetamol (1.5 g) in a randomized, crossover trial. Blood samples were taken at baseline and 10, 20, 30, 60, 90, and 120 minutes after the meals and glucose, insulin, TG, nonesterified fatty acids, glucagon-like polypeptide-1, glucose-independent polypeptide, and paracetamol (as a marker of gastric emptying) were measured in plasma or serum. The incremental areas under the curve of glucose, insulin, nonesterified fatty acid, incretins, and paracetamol levels were not significantly different between the meals. Plasma TG incremental area under the curve was 44% lower after the TOSO meal at a marginal level of significance (P = .06) in the total study population and was significantly (P = .04) and 61% lower in those of median age and younger (n = 11). These data suggest that ingestion of TOSO may acutely decrease plasma TG mainly in younger individuals and does not acutely affect glucose and insulin metabolism or gastric emptying in healthy subjects.

Oral but not intravenous glucose acutely decreases circulating interleukin-6 concentrations in overweight individuals.

BACKGROUND: Plasma interleukin-6 (IL-6) concentrations decrease acutely 1 h after ingestion of a glucose load or mixed meals and this may be mediated by an anti-inflammatory effect of insulin. The aim of the present study was to compare the effect of higher versus lower insulin levels on plasma IL-6 concentrations following oral compared with intravenous glucose administration in overweight/obese subjects. METHODS AND FINDINGS: Fifteen subjects (12 women and 3 men) with BMI >28 kg/m(2) were given an oral glucose load (75 g) followed a week later by an intravenous infusion of glucose aimed at matching plasma glucose concentrations during the oral glucose load. A week later, they drank a volume of water equivalent to the volume consumed with the oral glucose load. Plasma glucose, insulin, nonesterified fatty acids, and IL-6 concentrations and blood hematocrit were measured at 30 minute intervals for 2 h following each intervention. Plasma IL-6 decreased (13-20%) significantly (P = 0.009) at 30 min to 90 min following the oral glucose load and did not change significantly following the other two interventions. The incremental area under the curve for plasma IL-6 concentrations following oral intake of glucose was significantly lower compared with concentrations following intravenous glucose (P = 0.005) and water control (P = 0.02). Circulating insulin concentrations were significantly (P<0.001) and 2.8 fold higher following oral compared with intravenous glucose administration. CONCLUSIONS: These data show that plasma IL-6 concentrations did not decrease during isoglycemic, intravenous glucose administration suggesting that the markedly higher circulating insulin levels and/or gut-related factors may mediate the acute decrease in plasma IL-6 after oral glucose intake in overweight/obese subjects. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000491864.

Postprandial response of plasma IL-6 to isoenergetic meals rich in casein or potato singly and combined in obese women.

Milk consumption decreases inflammatory stress in overweight and obese subjects. Casein is the major protein in milk and enhances the secretion of insulin that has anti-inflammatory activity. The aim of the present study was to compare the acute effect of meals rich in casein and carbohydrate and a combination of both nutrients on postprandial plasma concentrations of IL-6, a marker of inflammation, in obese women. A total of twenty-five obese women aged 38-68 years consumed isoenergetic meals rich in potato (POT) or casein (CA) or a combination of both these meals (POT + CA), in random order in a cross-over trial. After an overnight fast, blood samples were collected before and at 1 and 4 h after the meals and circulating concentrations of IL-6, glucose, insulin and NEFA were measured. Plasma IL-6 concentrations increased significantly (P < 0·001) during 4 h after the meals. The AUC of postprandial IL-6 concentrations was not significantly (P = 0·77) different among the meals. Postprandial serum insulin concentration AUC was significantly higher during the POT + CA meal compared with the POT meal (P = 0·001) and the CA meal (P < 0·05), which in turn was significantly higher than the POT meal (P < 0·05). These data show that while ingestion of CA alone or combined with POT acutely increases circulating insulin concentrations, it does not appreciably alter the postprandial increase in plasma IL-6 concentrations in obese women.

Paraoxonase 1 activity in chylomicrons and VLDL: the effect of type 2 diabetes and meals rich in saturated fat and oleic acid.

Paraoxonase 1 (PON 1) has antioxidant and cardioprotective properties and is abnormally low in type 2 diabetic serum. This study aimed to determine the effect of type 2 diabetes and meals rich in saturated fat and oleic acid on PON1 activity in chylomicrons and very low density lipoproteins (VLDL). PON1 arylesterase activity was measured in chylomicrons and VLDL that were isolated in serum from 20 patients with type 2 diabetes and 20 age- and gender-matched, overweight controls 3 h after meals rich in cream or olive oil in a randomized, cross-over study. Chylomicron-PON1 activity (45%, P = 0.02), ratio chylomicron-PON1/chylomicron-triacylglycerides (TAG) (42%, P = 0.03) and chylomicron-protein content (46%, P < 0.001) were significantly lower in patients with type 2 diabetes compared with controls after the olive oil meal with comparable findings after the meal rich in cream. After ingestion of olive oil, chylomicron-PON1 activity was significantly higher in controls (P = 0.01) and marginally higher (P = 0.06) in diabetic patients and chylomicron-TAG were significantly (P < 0. 05) higher in both groups of subjects, compared with values after ingestion of cream. VLDL-PON1 increased (two-fold) significantly (P < 0.003) during both meals. Chylomicron-PON1 activity was correlated significantly with chylomicron-protein (P < 0.001, n = 40) and with postprandial serum PON1 activity (P ≤ 0.001, n = 40). Our data suggest that type 2 diabetes is associated with abnormally low chylomicron-PON1 activity after fatty meals and this may be linked to lower chylomicron-protein content and serum PON1 activity. Switching from saturated fat to olive oil in the meal increases PON1 activity in the chylomicron fraction largely due to increased numbers of chylomicron particles.

Assessment of markers of glycaemic control in diabetic patients with chronic kidney disease using continuous glucose monitoring.

AIM: Due to altered red blood cell survival and erythropoietin therapy glycated haemoglobin (HbA1c) may not accurately reflect long-term glycaemic control in patients with diabetes and chronic kidney disease (CKD). Glycated albumin (GA) and fructosamine are alternative markers of glycaemia. The aim of this study was to investigate the accuracy of HbA1c, GA and fructosamine as indicators of glycaemic control using continuous glucose monitoring. METHODS: HbA1c, GA and fructosamine concentrations were measured in 25 subjects with diabetic nephropathy (CKD stages 4 and 5 (estimated glomerular filtration rate <30 mL/min per 1.73 m(2) )) matched with 25 subjects with diabetes and no evidence of nephropathy. Simultaneous real-time glucose concentrations were monitored by continuous glucose monitoring over 48 h. RESULTS: GA correlated significantly to mean glucose concentrations in patients with and without CKD (r = 0.54 vs 0.49, P < 0.05). A similar relationship was observed with fructosamine relative to glucose. A poor correlation between HbA1c and glucose was observed with CKD (r = 0.38, P = ns) but was significant in the non-CKD group (r = 0.66, P < 0.001). The GA/HbA1c ratio was significantly higher in diabetic patients with CKD compared with controls (2.5 ± 0.4 vs 2.2 ± 0.4, P < 0.05). HbA1c values were significantly lower in CKD patients, relative to non-CKD patients at comparable mean glucose concentrations. CONCLUSION: HbA1c significantly underestimates glycaemic control in patients with diabetes and CKD stages 4 and 5. In severe CKD, GA more accurately reflects glycaemic control compared with fructosamine and HbA1c and should be the preferred marker of glycaemic control.

Prevalence of symptoms of severe asthma and allergies in Irish school children: an ISAAC protocol study, 1995-2007.

Childhood asthma is a recurring health burden and symptoms of severe asthma in children are also emerging as a health and economic issue. This study examined changing patterns in symptoms of severe asthma and allergies (ever eczema and hay fever), using the Irish International Study of Asthma and Allergies in Childhood (ISAAC) protocol. ISAAC is a cross-sectional self-administered questionnaire survey of randomly selected representative post-primary schools. Children aged 13-14 years were studied: 2,670 (in 1995), 2,273 (in 1998), 2,892 (in 2002-2003), and 2,805 (in 2007). Generalized linear modelling using Poisson distribution was employed to compute adjusted prevalence ratios (PR). A 39% significant increase in symptoms of severe asthma was estimated in 2007 relative to the baseline year 1995 (adjusted PR: 1.39 [95% CI: 1.14-1.69]) increasing from 12% in 1995 to 15.3% in 2007. Opposite trends were observed for allergies, showing a decline in 2007, with an initial rise. The potential explanations for such a complex disease pattern whose aetiological hypothesis is still evolving are speculative. Changing environmental factors may be a factor, for instance, an improvement in both outdoor and indoor air quality further reinforcing the hygiene hypothesis but obesity as a disease modifier must also be considered.

High-risk diabetic nephropathy patients: the outcome of evidence-based clinical practice in an outpatient clinic.

OBJECTIVE: A retrospective audit to assess the impact of a combined diabetes-renal consultant clinic over 10 years, on slowing the progression of diabetic nephropathy, using recognised markers of renal disease progression, including creatinine clearance and proteinuria. METHODS: 44 high-risk patients with diabetic nephropathy defined as having significant proteinuria (an elevated albumin creatinine ratio greater than 30 mg/mmol), and hypertension, a progressive rise in plasma creatinine or other evidence of diabetic microvascular disease or macrovascular disease, were identified. Sufficient follow up was defined as at least two data sets over a 12-month period prior to referral to the combined clinic, and at least 18 months of combined clinic follow up thereafter. RESULTS: In this high risk group, GFR was falling at an average of 7.97 m/min/year (95% CI 9.83-6.10 ml/min/year) at the time of referral and following clinic intervention this was significantly reduced to 3.17 ml/min/year (95% CI 4.47-1.87 ml/min/year) over the duration of follow up. Blood pressure, glycaemic control and lipid status remained stable and close to current recommended guidelines. CONCLUSIONS: A combined diabetes-renal consultant clinic is an effective intervention to improve the outcome of high-risk diabetics with progressive diabetic nephropathy.

Anti-inflammatory effect of an insulin infusion in patients on maintenance haemodialysis: a randomized controlled pilot study.

AIM: A pilot study to investigate the anti-inflammatory effect of insulin in patients on maintenance haemodialysis. BACKGROUND: Elevated concentrations of pro-inflammatory and oxidative mediators are thought to contribute to the increased cardiovascular risk in haemodialysis. Insulin has been demonstrated to have anti-inflammatory properties and a continuous low-dose insulin infusion in critically ill patients is associated with improved outcomes. The anti-inflammatory effects of insulin in haemodialysis have not been investigated. METHODS: In a single-blind cross-over study, 11 stable, non-diabetic, haemodialysis patients received a continuous insulin infusion (Actrapid 2 IU/h) during a dialysis of 4 h or a conventional dialysis in random order. Normoglycaemia was maintained by a modified glucose dialysate and glucose infusion. Blood samples were collected at baseline, 1, 4, 6 and 24 h. C-reactive protein (CRP), tumour necrosis factor-α, interleukin-6, neopterin, vascular cell adhesion molecule 1, protein thiols, dityrosine and peroxides were measured. RESULTS: Insulin produced a significant reduction in median CRP over the immediate dialysis phase (confidence interval) by 6% (2-9% (95% CI), P=0.006) and an even greater decline at 24 h (19% (8-28%, 95% CI), P=0.001) compared with values of the conventional dialysis. No significant changes were observed in the other markers. Median glucose levels were comparable during both dialysis sessions. CONCLUSIONS: During haemodialysis, insulin may have a modest anti-inflammatory effect as evident by a reduction in CRP that appears to have a persistent effect over the next 24 h post dialysis. More studies are required to examine longer-term benefits as well as the potential role in more high-risk individuals.

Body mass index and waist circumference cutoffs to define obesity in indigenous New Zealanders.

BACKGROUND: The suggestion that body mass index (BMI) cutoffs to define obesity should differ in persons of Polynesian descent compared with Europeans is based principally on the observation that persons of Polynesian descent have a relatively higher proportion of lean body mass for a given BMI. OBJECTIVES: The objectives were to determine whether the relation between BMI, waist circumference, and metabolic comorbidity differs in the 2 major ethnic groups in New Zealand and to ascertain whether ethnicity-specific BMI and waist circumference cutoffs for obesity are justified for Maori (indigenous New Zealanders). DESIGN: Subjects included a convenience sample of 1539 men and women aged 17-82 y (47% Maori, 53% white) with measures of BMI, waist circumference, blood pressure, fasting insulin, glucose, and lipids. The sensitivity and specificity of BMI (in kg/m(2); 30 and 32), waist circumference (80 and 88 cm in women, 94 and 102 cm in men), and waist-to-height ratio (WHtR; > or =0.6) in relation to insulin sensitivity, insulin resistance, and the metabolic syndrome were determined. Receiver operating characteristic curves and areas under the curve (AUCs) were also calculated. RESULTS: No ethnic or sex differences between AUCs were observed for BMI, waist circumference, or WHtR, which showed that these anthropometric measures perform similarly in Maori and European men and women and correctly discriminate between those with and without insulin resistance or the metabolic syndrome 79-87% of the time. Any increase in specificity from a higher BMI cutoff of 32 in Maori was offset by appreciable reductions in sensitivity. CONCLUSION: These findings argue against having different BMI or waist circumference cutoffs for people of Polynesian descent.

The effect of glucose ingestion on inflammation and oxidative stress in obese individuals.

Ingestion of 75 g glucose during an oral glucose tolerance test (OGTT) increases systemic inflammation and oxidative stress in healthy subjects and patients with type 2 diabetes mellitus, but the effect in overweight/obese nondiabetic individuals is uncertain. The aim of the present study was to determine the effect of an OGTT on plasma concentrations of inflammatory cytokines and peroxides in 33 subjects with body mass index >27 kg/m(2). After an overnight fast, blood samples were taken from participants immediately before and at 30, 60, 90, and 120 minutes after ingestion of 75 g glucose. Plasma glucose, insulin, free fatty acid, interleukin (IL)-6, tumor necrosis factor alpha, and peroxides were measured during the tests. Plasma IL-6 concentrations decreased (13%) significantly (P < .001) at 30 and 60 minutes, whereas plasma peroxide concentrations decreased slightly (3%, P = .003) at 30 minutes during the tests. The 30-minute decrease in plasma IL-6 was correlated significantly and inversely with the concomitant increase in plasma insulin (r = -0.410, P = .02) and with the ratio of insulin to glucose at 30 minutes during the OGTT (r = -0.366, P = .04). These data suggest that plasma concentrations of IL-6 are acutely decreased possibly because of the predominance of the anti-inflammatory effect of hyperinsulinemia over the proinflammatory effect of hyperglycemia after ingestion of a large quantity of glucose in obese individuals.

The effect of rosiglitazone on oxidative stress and insulin resistance in overweight individuals.

OBJECTIVE: The purpose of this study was to examine the chronic effect of rosiglitazone on oxidative stress, inflammatory markers and hepatic risk factors for type 2 diabetes in overweight individuals. In addition we examined the effect of rosiglitazone on post-glucose challenge levels of glucose and insulin. RESEARCH DESIGN AND METHODS: Forty overweight individuals (BMI>27kg/m(2)) were randomized in a double blind fashion to receive 6 months treatment with either rosiglitazone 4mg/day or placebo. Primary endpoints were markers of oxidative stress (plasma peroxides), inflammatory markers (IL-6, TNF-alpha and CRP) and postprandial glucose metabolism (glucose and insulin). Secondary endpoints were changes in insulin resistance as measured by HOMA, first and second phase insulin secretion, adiponectin and effects on lipid and hepatic parameters. RESULTS: Plasma peroxides (-15%) decreased significantly during 6 months in the group that received rosiglitazone compared with placebo. Fasting plasma insulin concentrations decreased by 24% and HOMA increased by 35% in those receiving rosiglitazone. Plasma IL-6 (-25%), CRP (-55%) and GGT (-25%) concentrations declined significantly in the rosiglitazone group. Rosiglitazone increased plasma adiponectin by 81%. Treatment with rosiglitazone also resulted in significantly reduced first phase (-33%) and second phase (-20%) insulin release. CONCLUSIONS: In overweight non-diabetic people rosiglitazone reduces oxidative stress and improves insulin sensitivity. Rosiglitazone also improves first and second phase insulin secretion and reduces markers of inflammation and GGT.

Postprandial cytokine concentrations and meal composition in obese and lean women.

The aim of this study was to compare the acute effect of (i) meals rich in saturated fat, oleic acid, and alpha-linolenic acid and (ii) meals rich in starch and fiber on markers of inflammation and oxidative stress in obese and lean women. In a crossover study, 15 abdominally obese women (age, 54 +/- 9 years; BMI, 37.3 +/- 5.5 kg/m2) and 14 lean women (age, 53 +/- 10 years; BMI, 22.9 +/- 1.9 kg/m2) consumed meals rich in cream (CR), olive oil (OL), canola oil (CAN), potato (POT), and All-Bran (BRAN) in random order. Blood samples were collected before and up to 6 h after the meals and plasma interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-alpha), lipid peroxides (LPOs), free-fatty acids (FFAs), insulin, glucose, and cortisol were measured. Plasma IL-6 decreased significantly 1 h after the meals then increased significantly above baseline at 4h and 6h in obese women and at 6h in lean women. The incremental area under the curve (iAUC) for IL-6 was significantly (P = 0.02) higher in obese compared with lean women and was significantly lower following the high fiber BRAN meal compared with a POT meal (P = 0.003). Waist circumference (R = 0.491, P = 0.007) and cortisol AUC (R = -0.415, P = 0.03) were significant determinants of the magnitude of 6h changes in plasma IL-6 after the meals. These findings suggest that the postprandial response of plasma IL-6 concentrations may be influenced by the type of carbohydrate in the meal, central adiposity, and circulating cortisol concentrations in women.