Comparison of biofilm production and virulence genes distribution among human and canine isolates of Staphylococcus aureus.

Background: Staphylococcus aureus is an important human and animal pathogen that can cause a wide range of infections due to numerous virulence factors. Aims: The aim of this study was to compare biofilm formation ability with different virulence factors such as bacterial motility, genes encoding biofilm associated proteins, and Panton-Valentine leukocidin (PVL) among human and canine isolates of S. aureus. Methods: A total of 60 human (30 methicillin sensitive S. aureus (MSSA) and 30 methicillin resistant S. aureus (MRSA)) and 17 canine (all MSSA) isolates of S. aureus were tested for the capability of biofilm production, motility assay, and presence of genes encoding virulence factors: ica (encoding intercellular adhesion), bap (encoding biofilm-associated protein), fnbA (encoding fibronectin-binding protein A), cna (encoding collagen-binding protein), and pvl (encoding PVL). Results: Animal isolates of S. aureus performed better biofilm production than the human strains (P=0.042), as well as human MSSA compared to the MRSA isolates (P=0.013). Our results showed that cna, fnbA, and ica genes (67.5%, 66.2%, and 42.9%, respectively) were more prevalent than bap and pvl genes (0%, and 7.8%, respectively). The ica gene was significantly more prevalent in human isolates compared to animal isolates (n=31/60 vs. n=2/17, P=0.008), whereas the cna gene was more frequent in animal isolates than in human ones (n=15/17 vs. n=37/60, P=0.0201). Significant correlations were found between the biofilm formation of animal isolates, and the presence of fnbA (P=0.029) and ica genes (P=0.001). Conclusion: This study showed a correlation between biofilm production and the presence of certain biofilm-related genes in animal isolates, as well as stronger biofilm production among MSSA human and animal isolates.

Performance analysis and implementation of a scanning tunneling potentiometry setup: Toward low-noise and high-sensitivity measurements of the electrochemical potential.

Scanning tunneling potentiometry allows for studying charge transport on the nanoscale to relate the local electrochemical potential to morphological features of thin films or two-dimensional materials. To resolve the influence of atomic-scale defects on the charge transport, sub-µV sensitivity for the electrochemical potential is required. Here, we present a complete analysis of the noise in scanning tunneling potentiometry for different modes of operation. We discuss the role of various noise sources in the measurements and technical issues for both dc and ac detection schemes. The influence of the feedback controller in the determination of the local electrochemical potential is taken into account. Furthermore, we present a software-based implementation of the potentiometry technique in both dc and ac modes in a commercial scanning tunneling microscopy setup with only the addition of a voltage-controlled current source. We directly compare the ac and dc modes on a model resistor circuit and on epitaxial graphene and draw conclusions on the advantages and disadvantages of each mode. The effects of sample heating and the occurrence of thermal voltages are discussed.

Clinical Obesity Services in Public Hospitals in Australia: a position statement based on expert consensus.

We aimed to describe the current state of specialist obesity services for adults with clinically severe obesity in public hospitals in Australia, and to analyse the gap in resources based on expert consensus. We conducted two surveys to collect information about current and required specialist obesity services and resources using open-ended questionnaires. Organizational level data were sought from clinician expert representatives of specialist obesity services across Australia in 2017. Fifteen of 16 representatives of current services in New South Wales (n = 8), Queensland (n = 1), Victoria (n = 2), South Australia (n = 3), and the Australian Capital Territory (n = 1) provided data. The composition of services varied substantially between hospitals, and patient access to services and effective treatments were limited by strict entry criteria (e.g. body mass index 40 kg/m2 or higher with specific complication/s), prolonged wait times, geographical location (major cities only) and out-of-pocket costs. Of these services, 47% had a multidisciplinary team (MDT), 53% had an exercise physiologist/physiotherapist, 53% had a bariatric surgeon and 33% had pharmacotherapy resources. Key gaps included staffing components of the MDT (psychologist, exercise physiologist/physiotherapist) and access to publicly funded weight loss pharmacotherapy and bariatric surgery. There was consensus on the need for significant improvements in staff, physical infrastructure, access to services, education/training in obesity medicine and targeted research funding. Based on the small number of existing, often under-resourced specialist obesity services that are located only in a few major cities, the vast majority of Australians with clinically severe obesity cannot access the specialist evidence based treatments needed.

Examining the association between depression and obesity during a weight management programme.

The prevalence of depression in those with obesity is reported to be as high as double that in individuals of normal weight. There is potentially a bi-directional relationship between obesity and depression. Some research has suggested that depression results in weight gain and obesity, and other studies have suggested that those with obesity are more likely to develop depression at a later stage. The aim of this study was to investigate the association of depression symptoms with weight change over a 12-month study. Seventy participants undertook a 3-month lifestyle (diet and exercise) weight loss intervention, and were followed up as part of a 12-month study. Participants completed the Beck Depression Inventory-II (BDI-II) and had their body weight measured throughout the study. Baseline body mass index (BMI) of participants (mean ± standard deviation [SD]) was 31.1 ± 3.9 kg m-2 , body weight was 89.4 ± 16.1 kg, and age was 45.4 ± 11.1 years; 63% of the cohort were female. The mean weight change from baseline to 3 months was -5.2% (±SD 4.3%), and from baseline to 12 months was -4.2% (±SD 6.1%). There was a significant decrease in BDI-II scores over the 12-month study, and a 1-unit decrease in BDI-II score was associated with a further decrease in body weight of -0.4%. The current study indicated that weight loss was associated with improvements in mood for non-clinically depressed individuals with obesity, and these improvements persisted during a period of 3-12 months of follow-up.

Investigating general medication prescription by general practitioners during a 12-month randomized controlled weight loss trial.

Much healthcare expenditure is on pharmaceutical drugs. Expenditure on medications has increased both in absolute terms, and as a proportion of total health expenditure. No previous studies have investigated the prescribing costs by general practitioners when managing patients during a weight loss intervention. This study evaluated the medication costs by individual class during a 1-year study in which 268 participants were randomized to one of two weight loss programmes, either standard care (SC) as defined by national guidelines, or a commercial provider (Weight Watchers) (CP). The baseline body mass index of participants (mean ± standard deviation) was 32.0 ± 2.5 kg m-2 , their body weight was 87.5 ± 11.8 kg, and age 47.4 ± 11.7 years. Weight loss for the SC and CP groups was -2.6 and -6.1 kg, respectively (between group difference; P < 0.0001). The greater weight loss in the CP group compared to SC was accompanied by larger reductions in waist circumference and fat mass. The CP group also had significantly greater improvements than SC in high-density lipoprotein cholesterol. Despite SC participants being prescribed and spending more on medications than the CP group with no better weight or metabolic outcomes, this was not of statistical significance. For both groups the highest proportion of prescriptions (≥30% of medications) was for control of risk factors for cardiovascular disease. In conclusion, this study indicates that obesity treatment via a shared care approach with a CP results in greater weight loss and some better clinical outcomes, but despite lower medication costs overall, this was not significant when compared to SC treatment.

Fast versus slow weight loss: development process and rationale behind the dietary interventions for the TEMPO Diet Trial.

OBJECTIVE AND METHODS: Finding effective solutions to curb the obesity epidemic is a great global public health challenge. The need for long-term follow-up necessitates weight loss trials conducted in real-world settings, outside the confines of tightly controlled laboratory or clinic conditions. Given the complexity of eating behaviour and the food supply, this makes the process of designing a practical dietary intervention that stands up to scientific rigor difficult. Detailed information about the dietary intervention itself, as well as the process of developing the final intervention and its underlying rationale, is rarely reported in scientific weight management publications but is valuable and essential for translating research into practice. Thus, this paper describes the design process and underlying rationale behind the dietary interventions in an exemplar weight loss trial - the TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimal metabolic health and body composition in Obesity). This trial assesses the long-term effects of fast versus slow weight loss on adiposity, fat free mass, muscle strength and bone density in women with obesity (body mass index 30-40 kg m-2) that are 45-65 years of age, postmenopausal and sedentary. RESULTS AND CONCLUSIONS: This paper is intended as a resource for researchers and/or clinicians to illustrate how theoretical values based on a hypothesis can be translated into a dietary weight loss intervention to be used in free-living women of varying sizes.

Hypoglycaemia in cystic fibrosis in the absence of diabetes: A systematic review.

BACKGROUND: Hypoglycaemia in CF in the absence of diabetes or glucose lowering therapies is a phenomenon that is receiving growing attention in the literature. These episodes are sometimes symptomatic and likely have variable aetiologies. Our first aim was to conduct a systematic review of the literature to determine what is known about hypoglycaemia in CF. Our second aim was to assess evidence based guidelines for management strategies. METHODS: A comprehensive search of databases and guideline compiler entities was performed. Inclusion criteria were primary research articles and evidence based guidelines that referred to hypoglycaemia in CF in the absence of insulin treatment or other glucose lowering therapies. RESULTS: A total of 11 studies (four manuscripts and seven abstracts) and five evidence-based guidelines met the inclusion criteria. Prevalence rates of hypoglycaemia unrelated to diabetes varied between studies (7-69%). Hypoglycaemia was diagnosed during oral glucose tolerance testing or continuous glucose monitoring (CGM). Associations between hypoglycaemia and clinical parameters of BMI, lung function, liver disease and pancreatic insufficiency were measured in some studies. There was no unifying definition of hypoglycaemia in the absence of diabetes. Only two evidence based guidelines reported possible management strategies. CONCLUSION: The systematic review found limited data on this clinical problem and supports the need for high quality methodological studies that are able to describe the experience and the aetiology(ies) of hypoglycaemia in CF.

The effects of high-fat feeding on physical function and skeletal muscle extracellular matrix.

Skeletal muscle extracellular matrix (ECM) remodelling has been proposed as a feature of the pathogenic milieu associated with obesity and metabolic dysfunction. Whether muscle ECM is associated with impaired physical function in obese conditions is unknown. C57BL/6 mice were fed a high-fat diet (HFD) or chow for 5, 10 and 25 weeks. Non-invasive physiological tests (hang wire, hang mesh and grip strength) to assess neuromuscular function and motor co-ordination were performed. Genes related to ECM structure (COL1, COL3, COL6A2, SPARC), growth factors (TGFB1, TGFB2, CTGF, VEGF) and muscle function (DMD (Dp147), CPN3, DAG1) were measured in gastrocnemius muscle using real-time PCR and COL1, 3 and 6 protein were measured by western immunoblot. Compared with chow, HFD mice had two to six-fold lower muscle strength (hang wire test; raw data and multiplied by body weight) at all time-points (P<0.001) and two-fold lower hang mesh and grip strength at 10 weeks (P<0.05). At 5 weeks, COL1, COL3 and COL6 gene expression, but not protein levels were three to eight-fold lower in HFD compared with chow. In the HFD group at 5 weeks, greater COL3 and 6 gene expression were associated with poorer hang wire performance. For the first time, our results demonstrate links between muscle ECM structure and physical function in obesity.

Intra-ventral tegmental area microinjections of urotensin II modulate the effects of cocaine.

Although the peptide urotensin II (UII) has well studied direct actions on the cardiovascular system, the UII receptor (UIIR) is expressed by neurons of the hindbrain. Specifically, the UIIR is expressed by the cholinergic neurons of the laterodorsal tegmentum (LDTg) and the pedunculopontine tegmentum (PPTg). These neurons send axons to the ventral tegmental area (VTA), for which the PPTg and LDTg are the sole source of acetylcholine. Therefore, it was hypothesized that UIIR activation within the VTA would modulate reward-related behaviors, such as cocaine-induced drug seeking. Intra-VTA microinjections of UII at high concentrations (1 nmole) established conditioned place preference (CPP), but also blocked cocaine-mediated CPP (10 mg/kg). When rats received systemic sub-effectual doses of cocaine (7.5 mg/kg) with intra-VTA injections of 1 or 10 pmole of UII CPP was formed. Furthermore, the second endogenous ligand for the UIIR, urotensin II-related peptide, had the same effect at the 10 pmole dose. The effects of low doses of UII were blocked by pretreatment with the UIIR antagonist SB657510. Furthermore, it was found that intra-VTA UII (10 pmole) further increased cocaine-mediated (7.5 mg/kg) rises in electrically evoked dopamine in the nucleus accumbens. Our study has found that activation of VTA-resident UIIR produces observable behavioral changes in rats, and that UIIR is able to modulate the effects of cocaine. In addition, it was found that UIIR activation within the VTA can potentiate cocaine-mediated neurochemical effects. Therefore, the coincident activation of the UII-system and cocaine administration may increase the liability for drug taking behavior.

Do ketogenic diets really suppress appetite? A systematic review and meta-analysis.

Very-low-energy diets (VLEDs) and ketogenic low-carbohydrate diets (KLCDs) are two dietary strategies that have been associated with a suppression of appetite. However, the results of clinical trials investigating the effect of ketogenic diets on appetite are inconsistent. To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, we conducted a systematic literature search and meta-analysis of studies that assessed appetite with visual analogue scales before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD. Individuals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and individuals adhering to KLCD were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people. Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although individuals may indeed feel slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite. Future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate-containing foods into the diet.

Enhanced consumption of salient solutions following pedunculopontine tegmental lesions.

Rats with lesions of the pedunculopontine tegmental nucleus (PPTg) reliably overconsume high concentration sucrose solution. This effect is thought to be indicative of response-perseveration or loss of behavioral control in conditions of high excitement. While these theories have anatomical and behavioral support, they have never been explicitly tested. Here, we used a contact lickometer to examine the microstructure of drinking behavior to gain insight into the behavioral changes during overconsumption. Rats received either excitotoxic (ibotenic acid) damage to all PPTg neuronal subpopulations or selective depletion of the cholinergic neuronal sub-population (diphtheria toxin-urotensin II (Dtx-UII) lesions). We offered rats a variety of pleasant, neutral and aversive tastants to assess the generalizability and specificity of the overconsumption effect. Ibotenic-lesioned rats consumed significantly more 20% sucrose than sham controls, and did so through licking significantly more times. However, the behavioral microstructure during overconsumption was unaffected by the lesion and showed no indications of response-perseveration. Furthermore, the overconsumption effect did not generalize to highly consumed saccharin. In contrast, while only consuming small amounts of quinine solution, ibotenic-lesioned rats had significantly more licks and bursts for this tastant. Selective depletion of cholinergic PPTg neurons had no effect on consumption of any tastant. We then assessed whether it is the salience of the solution which determines overconsumption by ibotenic-lesioned rats. While maintained on free-food, ibotenic-lesioned rats had normal consumption of sucrose and hypertonic saline. After mild food deprivation ibotenic PPTg-lesioned rats overconsumed 20% sucrose. Subsequently, after dietary-induced sodium deficiency, lesioned rats consumed significantly more saline than controls. These results establish that it is the salience of the solution which is the determining factor leading to overconsumption following excitotoxic PPTg lesion. They also find no support for response-perseveration contributing to this effect. Results are discussed in terms of altered dopamine (DA) and salience signaling.

Natural radioactivity in lignite samples from open pit mines "Kolubara", Serbia--risk assessment.

Coal as fossil fuel mainly contains naturally occurring radionuclides from the uranium and thorium series and (40)K. Use of coal, primarily in industry, as a result has dispersion of radioactive material from coal in and through air and water. The aim of this study was to determine the activity concentrations of natural radionuclides in coal samples from open pit mines "Kolubara" and to evaluate its effect on population health. The results showed that all measured and calculated values were below the limits recommended in international legislation.

Fat oxidation, body composition and insulin sensitivity in diabetic and normoglycaemic obese adults 5 years after weight loss.

OBJECTIVE: To investigate whether normal glucose-tolerant and type II diabetic overweight adults differ in response to weight regain with regard to substrate oxidation and metabolic parameters. METHODS: A total of 15 overweight-obese subjects: seven normal glucose tolerant (NGT) and eight with type II diabetes (DM) were restudied 5 y after significant weight loss. Prediet, after 28 days calorie restriction and at 5 y, subjects were characterised for weight, height, waist-to-hip ratio (WHR) and body composition by dual-energy X-ray absorptiometry. Fasting glucose, insulin, leptin and lipid levels were measured and subjects underwent euglycaemic-hyperinsulinaemic clamp (insulin 0.25 U/kg/h for 150 min). Indirect calorimetry was performed resting and in the final 30 min of the clamp. Dietary assessment was by 4-day diet-diary. RESULTS: Both NGT and DM groups regained weight at 5 y and were not different to prediet. Total body fat (%) and WHR were higher at 5 y compared to prediet in both groups. Fasting glucose was increased in NGT subjects at 5 y, and fasting insulin was higher in both groups at 5 y compared to prediet. Insulin sensitivity (GIR) was similar at 5 y compared to prediet, but at 5 y DM subjects were more insulin resistant than NGT subjects. At 5 y, both DM and NGT groups had significantly reduced basal fat oxidation and no significant suppression of fat oxidation with insulin. Clamp respiratory quotient levels at 5 y were significantly higher in NGT compared to DM subjects. CONCLUSION: Reduced basal fat oxidation, and reduced variation in substrate oxidation in response to insulin develop with fat regain and fasting hyperinsulinaemia in both NGT and DM obese adults.

[Therapeutic value of antioxidants and calcium channel blockers in patients in the acute phase of closed head injuries]. / Terapijska vrijednost antioksidanasa i blokatora kalcijumski kanala kod bolesnika sa zatvorenom povredom glave u akutnoj fazi.

Knowing that uncontrolled calcium signalization with excessive production of reactive oxidative matters is present in case of neurotrauma, aim of the investigation was to establish therapeutic value of combined administration of antioxidants (AO) and calcium channel blockers (CCB) in patients with closed head injury (CHI). Investigation comprised 120 patients with CHI who received AO (vitamins C and E) parenterally during 10 days and CCB (nimodipine), and control group was comprised of 60 patients with CHI who did not receive these medicinals in therapeutic program. We have established the influence of the therapy on neurologic and functional deficiency and consciousness disorder, respectively. Results of the investigation confirmed better recovery of all three observed parameters (degree of neurologic deficiency, degree of functional deficiency and consciousness disorder) in a group of patients receiving AO and CCB, which was statistically significant. It can be concluded that the administration of AO and CCB in patients with CHI in the acute phase should be included into therapeutic program of this significant clinical syndrome.

Obesity: genes, glands or gluttony?

Distribution as well as amount of fat has health implications; central abdominal fat seems to be the major contributor to insulin resistance and risk of diabetes, hypertension and cardiovascular disease. Physical activity and diet affect overall adiposity; moreover, exercise specifically reduces visceral fat. The sexes differ in fat distribution; in particular, pre-menopausal women, despite greater overall adiposity, have much less visceral fat than men. There is a strong genetic determination of overall obesity and central abdominal adiposity. Genes regulating obesity (e.g. Ob) could modulate appetite, satiety, metabolic rate or physical activity. Moderate obesity probably results from interaction between genetic predisposition and an environment of abundant calories and reduced physical activity. Single gene mutations are being identified in a few morbidly obese people; however, the common genetic predisposition for obesity may relate to more subtle variations in regulatory controls. Diet and exercise are effective for some, but the response is often disappointing. Definition of pathways controlling appetite, metabolic rate and lipid metabolism may generate improved pharmacological compounds. Education and availability of lower-energy foods may help, but more radical approaches may be needed, such as environmental restructuring to increase physical activity. The problem is great, but failure will mean intolerably increased health costs.

The determinants of glycemic responses to diet restriction and weight loss in obesity and NIDDM.

OBJECTIVE: To examine the mechanisms by which weight loss improves glycemic control in overweight subjects with NIDDM, particularly the relationships between energy restriction, improvement in insulin sensitivity, and regional and overall adipose tissue loss. RESEARCH DESIGN AND METHODS: Hyperinsulinemic glucose clamps were performed in 20 subjects (BMI = 32.0 +/- 0.5 [SEM] kg/m2, age = 48.4 +/- 2.7 years) with normal glucose tolerance (NGT) (n = 10) or mild NIDDM (n = 10) before and on the 4th (d4) and 28th (d28) days of a reduced-energy (1,100 +/- 250 [SD] kcal/day) formula diet. Body composition changes were assessed by dual energy x-ray absorptiometry and insulin secretory changes were measured by insulin response to intravenous glucose before and after weight loss. RESULTS: In both groups, energy restriction (d4) reduced fasting plasma glucose (FPG) (delta FPG: NGT = -0.4 +/- 0.2 mmol/l and NIDDM = -1.1 +/- 0.03 mmol/l, P = 0.002), which was independently related to reduced carbohydrate intake (partial r = 0.64, P = 0.003). There was a marked d4 increase in percent of insulin suppression of hepatic glucose output (HGO) in both groups (delta HGO suppression: NGT = 28 +/- 15% and NIDDM = 32 +/- 8%, P = 0.002). By d28, with 6.3 +/- 0.4 kg weight loss, FPG was further reduced (d4 vs. d28) in NIDDM only (P = 0.05), and insulin sensitivity increased in both groups (P = 0.02). Only loss of abdominal fat related to improvements in FPG (r = 0.51, P = 0.03) and insulin sensitivity after weight loss (r = 0.48, P = 0.05). In contrast to insulin action, there were only small changes in insulin secretion. CONCLUSIONS: Both energy restriction and weight loss have beneficial effects on insulin action and glycemic control in obesity and mild NIDDM. The effect of energy restriction is related to changes in individual macronutrients, whereas weight loss effects relate to changes in abdominal fat.

Beneficial effect on average lipid levels from energy restriction and fat loss in obese individuals with or without type 2 diabetes.

OBJECTIVE: The risk of cardiovascular disease in type 2 diabetes is greater than is accounted for by conventional risk factors. We investigated whether energy restriction or modest fat loss improved the lipid profile in obese subjects with and without type 2 diabetes. The relationship of site of adipose tissue loss to lipid changes was also examined. RESEARCH DESIGN AND METHODS: Lipid levels were measured in 18 subjects with normal glucose tolerance (NGT) (n = 9, BMI = 31.5 +/- 0.8 [SEM] kg/m2) or type 2 diabetes (n = 9, BMI = 31.8 +/- 0.7) before and on the 4th (d4) and 28th (d28) days of a hypocaloric formula diet. Body composition was assessed with dual energy X-ray absorptiometry on d0 and d28. RESULTS: Mean daily energy intake during the diet was 1,100 +/- 60 kcal (33% protein, 38% carbohydrate, and 29% fat). Mean weight loss was 6.2 +/- 0.4 kg. Initial lipid profiles were similar in subjects with or without diabetes, and diabetes did not affect the responses. Dietary intervention resulted in early (d4) and late (d28) changes. Energy restriction (d4) reduced VLDL cholesterol and total triglyceride (TG) concentrations and increased LDL particle size. LDL TG, and LDL apolipoprotein B (apoB) concentrations. Reduction in central abdominal fat (but not other body fat) was correlated with a less atherogenic lipid profile: delta abdominal fat versus delta LDL free cholesterol, r = 0.65, P = 0.006 and versus delta apoB, r = 0.64, P = 0.008. CONCLUSIONS: Even in obese subjects with an average lipid profile, modest weight loss reduces atherogenicity, independently of type 2 diabetes, and abdominal fat loss is specifically related to such improvements.

Carbohydrate intake and short-term regulation of leptin in humans.

The response of serum leptin to short (4 days) and prolonged (28 days) energy restriction (50% reduction in energy intake) was determined in 18 (9 male, 9 female) moderately obese humans (body mass index 32.0 +/- 0.6 kg/m2 mean +/- SEM), 9 of whom had mild non-insulin-dependent diabetes mellitus (NIDDM). Body composition was assessed before and at the end of the energy restriction using DEXA. The subjects lost a measured 2.6 +/- 0.4 kg of body fat after 28 days and an estimated 0.3 kg at 4 days. Serum leptin fell to 64 +/- 3% of baseline levels at day 4 and further to 46 +/- 4% at day 28. In a multiple correlation analysis, the change in leptin concentration at day 4 was significantly related to the change in dietary carbohydrate intake (partial r = 0.68, p < 0.005) but not to changes in fat (r = 0.12) or protein (r = 0.02) intakes. There was a 1:1 relationship between the changes in leptin and dietary carbohydrate (regression slope = 1.0 +/- 0.3). Gender, or the presence of NIDDM had no effects on these responses. This pronounced fall in serum leptin in association with reduced carbohydrate intake before substantial loss of body fat suggests a role for leptin in defending the body's carbohydrate stores and implicates leptin in the satiating effects of carbohydrate. Dietary or other interventions which maintain leptin levels during weight reduction may lead to improvements in weight loss.

Importance of early insulin levels on prandial glycaemic responses and thermogenesis in non-insulin-dependent diabetes mellitus.

To examine the effect of different profiles of insulin administration on glycaemia and thermogenesis, we studied 10 subjects with mild non-insulin-dependent diabetes mellitus on four occasions after a standard mixed meal: (1) with no supplementary insulin (control), (2) with intravenous insulin (1.8U over 15 min = short), (3) as for short but extended over 30 min to simulate the normal initial rise in portal vein insulin levels (medium), (4) as for medium with additional insulin to normalize the profile from 30-60 min (3.6U over 60 min, long). All studies in which supplemental insulin was administered lowered the integrated glucose response above baseline versus the control study (short 76%, medium 71%, and long 56% of control, p = 0.003). The insulin infusions also increased the non-protein respiratory quotient in the first hour following the meal (0.82 +/- 0.01 (control) vs 0.87 +/- 0.01 (short), 0.86 +/- 0.01 (medium) and 0.87 +/- 0.01 (long), p = 0.003) and augmented thermogenesis (7.6 +/- 1.5 (control) vs 10.5 +/- 2.9 (short), 13.0 +/- 1.9 (medium) and 13.2 +/- 2.8% (long), p = 0.02). Total integrated insulin area above baseline was significantly greater in the long study (short 121, medium 111 vs long 179% of control, p = 0.02). Thus the greatest glycaemic benefit in relation to insulinaemia was obtained with the two shorter insulin infusions (short and medium). In conclusion, this study confirms the role of early prandial insulin secretion (or delivery) in limiting prandial glycaemia in NIDDM and increasing thermogenesis and highlights the pivotal role of the timing of elevation of insulin levels in modulating hyperglycaemia and hyperinsulinaemia.