A state of subclinical systemic inflammation is characteristically present in obesity/insulin resistance and type 2 diabetes mellitus (T2DM). The aim of the study was to develop an integrated measure ...of the circulating cytokines involved in the subclinical systemic inflammation and evaluate its relation with whole-body insulin sensitivity and glucose metabolism in T2DM. T2DM patients (
n
= 17, M/F 13/4, age = 55.0 ± 1.7 years, BMI = 33.5 ± 1.5 kg/m
2
, HbA
1c
= 7.7 ± 0.3 %) and normal glucose-tolerant (NGT) subjects (
n
= 15, M/F 7/8, age = 49.1 ± 2.5 years, BMI = 31.8 ± 1.2 kg/m
2
, HbA
1c
= 5.6 ± 0.1 %) were studied in a cross-sectional design. Whole-body insulin sensitivity was quantified by the euglycemic clamp. Beta-cell function disposition index (DI) was calculated using insulin and glucose values derived from an oral glucose tolerance test and the euglycemic clamp. Body fat mass was evaluated by dual-energy X-ray absorptiometry. Plasma cytokine TNF-α, IL-6, MCP-1, osteopontin, fractalkine and adiponectin values were divided into quintiles. A score ranging from 0 (lowest quintile) to 4 (highest quintile) was assigned. The inflammatory score (IS) was the sum of each cytokine score from which adiponectin score was subtracted in each study subject. Inflammatory cytokine levels were all higher in T2DM. IS was higher in T2DM as compared to NGT (10.0 ± 1.1 vs. 4.8 ± 0.8;
p
< 0.001). IS positively correlated with fasting plasma glucose (
r
= 0.638,
p
< 0.001), 1-h plasma glucose (
r
= 0.483,
p
= 0.005), 2-h plasma glucose (
r
= 0.611,
p
< 0.001) and HbA1c (
r
= 0.469,
p
= 0.007). IS was inversely correlated with insulin sensitivity (
r
= −0.478,
p
= 0.006) and DI (
r
= −0.523,
p
= 0.002). IS did not correlate with BMI and body fat mass. IS was an independent predictor of fasting plasma glucose and had a high sensibility and sensitivity to predict insulin resistance (
M/I
< 4). A state of subclinical inflammation defined and quantifiable by inflammatory score including TNF-α, IL-6, MCP-1, osteopontin, fractalkine and adiponectin is associated with both hyperglycemia and whole-body insulin resistance in T2DM.
Background and aims
The role of overweight and obesity in the development of atrial fibrillation (AF) is well established; however, the differential effect on the occurrence and recurrence of AF ...remains uncertain. The aim of this review is to compare the effect of underweight and varying degrees of obesity on onset of AF and in recurrent post-ablation AF, and, when possible, in relation to sex.
Methods
A systematic literature search was conducted in PubMed, Embase, and Cochrane Library from inception to January 31, 2023. Studies reporting frequency of newly-diagnosed AF and of recurrent post-ablation AF in different BMI categories, were included. 3400 records were screened and 50 met the inclusion criteria. Standardized data search and abstraction were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. Data were extracted from the manuscripts and were analyzed using a random effect model. The outcome was the occurrence of AF in population studies and in patients undergoing ablation.
Results
Data from 50 studies were collected, of which 27 for newly-diagnosed AF and 23 for recurrent post-ablation AF, for a total of 15,134,939 patients, of which 15,115,181 in studies on newly-diagnosed AF and 19,758 in studies on recurrent post-ablation AF. Compared to normal weight, the increase in AF was significant (
p
< 0.01) for overweight, obese, and morbidly obese patients for newly-diagnosed AF, and for obese and morbidly obese patients for recurrent post-ablation AF. Newly-diagnosed AF was more frequent in obese female than obese male patients.
Conclusion
The effect of increased BMI was greater on the onset of AF, and obese women were more affected than men.
Display omitted
Type 2 diabetes mellitus and arterial hypertension are major cardiovascular risks factors which shares metabolic and haemodynamic abnormalities as well as pathophysiological ...mechanisms. The simultaneous presence of diabetes and arterial hypertension increases the risk of left ventricular hypertrophy, congestive heart failure, and stroke, as compared to either condition alone. A number of guidelines recommend lifestyle measures such as salt restriction, weight reduction and ideal body weight mainteinance, regular physical activity and smoking cessation, together with moderation of alcohol consumption and high intake of vegetables and fruits, as the basis for reduction of blood pressure and prevention of CV diseases. Despite the availability of multiple drugs effective for hypertension, BP targets are reached in only 50 % of patients, with even fewer individuals with T2DM-achieving goals. It is established that new emerging classes of type 2 diabetes mellitus treatment, SGLT2 inhibitors and GLP1-receptor agonists, are efficacious on glucose control, and safe in reducing HbA1c significantly, without increasing hypoglycemic episodes. Furthermore, in recent years, many CVOT trials have demonstrated, using GLP1-RA or SGLT2-inihibitors compared to placebo (in combination with the usual diabetes medications) important benefits on reducing MACE (cardio-cerebral vascular events) in the diabetic population. In this hypothesis-driven review, we have examined the anti-hypertensive effects of these novel molecules of the two different classes, in the diabetic population, and suggest that they could have an interesting ancillary role in controlling blood pressure in type 2 diabetic patients.
Purpose
Childhood obesity is on the rise worldwide increasing the risk for metabolic, cardiovascular and liver diseases in children. Eating habits and lifestyle changes are currently the standard of ...care for treating pediatric obesity. Our study aimed to determine the impact of a dietary intervention based on the Mediterranean Diet (MD) and the Health Eating Plate, on anthropometric and metabolic parameters in obese and overweight boys.
Methods
We studied 126 overweight/obese boys with anthropometric measurements, blood biochemistry and nutrient intakes evaluation by means of Food Frequency Questionnaire (FFQ) at baseline, at 6 and 12 months after a nutritional–behavioral intervention.
Results
We observed a significant reduction in energy, macronutrients and micronutrients intakes. BMI-SDS significantly decreased after 1 year with the proportion of obese boys decreasing by 33% and of overweight boys by 41%, while also all fat mass measures decreased both in obese and overweight individuals. In obese boys, ALT decreased significantly after 1-year nutritional intervention and these changes correlated with BMI-SDS reduction. Insulin-resistance and secretion indexes correlated with fat mass and BMI-SDS. In obese boys, significant changes were observed at 6 months for insulin concentrations, 1/HOMA-IR and QUICKI. With regard to the lipid profile, significant decreases were observed for total and LDL cholesterol in obese boys.
Conclusion
Metabolic and anthropometric risk factors in overweight and obese boys can be improved by a nutritional–behavioral intervention of 1-year duration.
The use of bariatric surgery for the treatment of morbid obesity has increased annually for the last decade. Although many studies have demonstrated the efficacy and durability of bariatric surgery ...for weight loss, there are limited data regarding long-term side effects of these procedures. Recently, there has been an increased focus on the impact of bariatric surgery on bone metabolism. Bariatric surgery utilizes one or more of three mechanisms of action resulting in sustained weight loss. These include restriction (gastric banding, vertical banded gastroplasty and sleeve gastrectomy), malabsorption surgery with or without associated restriction (Roux en Y gastric bypass, duodenal switch, biliopancreatic diversion and jejunoileal bypass) and changes in gut-derived hormones that control energy metabolism also referred to as neuro-hormonal control of energy metabolism (Roux en Y gastric bypass, duodenal switch, biliopancreatic diversion, jejunoileal bypass, surgical procedures as above and gastric sleeve). Weight reduction has been associated with increased bone resorption but the mechanisms behind this have not yet been fully elucidated. Each of the mechanisms of action of bariatric surgery (restriction, malabsorption, neuro-hormonal control of energy metabolism) may uniquely affect bone resorption. In this paper we will review the current state of knowledge regarding the relationship between bariatric surgery and bone metabolism with emphasis on possible mechanisms of action such as malnutrition, hormonal interactions and mechanical unloading of the skeleton. Further, we suggest a future research agenda.
In this study, we describe the results of virological investigations carried out on cases of gastroenteritis reported in different communities within a 2-year pilot surveillance programme (January ...2012 to December 2013) in the autonomous province of Bolzano (Northern Italy). Among the 162 norovirus (NoV)-positive cases out of 702 cases investigated, 76 were grouped in nine suspected outbreaks, 37 were hospital-acquired and 49 were community-acquired sporadic cases. NoV infections were found in all age groups in outbreak and community-acquired cases, while the highest peak of hospital-acquired infections occurred in the elderly. Sequence analyses helped to identify suspected outbreaks both in the community and in hospital wards. Although GII.4 is the predominant genotype, sequence data confirmed that at least seven genotypes circulate causing sporadic cases. Findings in this study confirmed the relevance of NoV infections as a cause of outbreaks, and impact of NoV infections in community-acquired sporadic cases in adults that are rarely described because of a lack of reporting.
The identification of brown/beige adipose tissue in adult humans has motivated the search for methods aimed at increasing its thermogenic activity as an approach to treat obesity. In rodents, the ...brown adipose tissue is under the control of sympathetic signals originating in the hypothalamus. However, the putative connection between the depots of brown/beige adipocytes and the hypothalamus in humans has never been explored. The objective of this study was to evaluate the response of the hypothalamus and brown/beige adipose tissue to cold stimulus in obese subjects undergoing body mass reduction following gastric bypass.
We evaluated twelve obese, non-diabetic subjects undergoing Roux-in-Y gastric bypass and 12 lean controls. Obese subjects were evaluated before and approximately 8 months after gastric bypass. Lean subjects were evaluated only at admission. Subjects were evaluated for hypothalamic activity in response to cold by functional magnetic resonance, whereas brown/beige adipose tissue activity was evaluated using a (F 18) fluorodeoxyglucose positron emisson tomography/computed tomography scan and real-time PCR measurement of signature genes.
Body mass reduction resulted in a significant increase in brown/beige adipose tissue activity in response to cold; however, no change in cold-induced hypothalamic activity was observed after body mass reduction. No correlation was found between brown/beige adipose tissue activation and hypothalamus activity in obese subjects or in lean controls.
In humans, the increase in brown/beige adipose tissue activity related to body mass reduction occurs independently of changes in hypothalamic activity as determined by functional magnetic resonance.
Thiazolidinediones (TZDs) enhanced body weight (BW) partially by increased adipogenesis and hyperphagia. Neuronal PPARγ knockout mice on high-fat diet (HFD) are leaner because of enhanced leptin ...response, although it could be secondary to their leanness. Thus, it still is an open question how TZDs may alter energy balance. Multiple factors regulate food intake (FI) and energy expenditure (EE), including anorexigenic hormones as insulin and leptin. Nonetheless, elevated hypothalamic AMPK activity increases FI and TZDs increase AMPK activity in muscle cells. Thus, the aim of the present study was to investigate whether Pioglitazone (PIO) treatment alters hypothalamic insulin and leptin action/signaling, AMPK phosphorylation, and whether these alterations may be implicated in the regulation of FI and EE.
Swiss mice on HFD (2 months) received PIO (25 mg kg(-1) per day-gavage) or vehicle for 14 days. AMPK and AdipoR1 were inhibited via Intracerebroventricular injections using Compound C (CompC) and small interference RNA (siRNA), respectively. Western blot, real-time PCR and CLAMS were done.
PIO treatment increased BW, adiposity, FI, NPY mRNA and decreased POMC mRNA expression and EE in HFD mice. Despite higher adiposity, PIO treatment improved insulin sensitivity, glucose tolerance, decreased insulin and increased adiponectin serum levels. This result was associated with, improved insulin and leptin action/signaling, decreased α2AMPK(Ser491) phosphorylation and elevated Acetyl-CoA carboxylase and AMPK(Thr172) phosphorylation in hypothalamus. The inhibition of hypothalamic AMPK with CompC was associated with decreased adiposity, FI, NPY mRNA and EE in PIO-treated mice. The reduced expression of hypothalamic AdipoR1 with siRNA concomitantly with PIO treatment reverted PIO induced obesity development, suggesting that adiponectin may be involved in this effect.
These results demonstrated that PIO, despite improving insulin/leptin action in hypothalamus, increases FI and decreases EE, partially, by activating hypothalamic adiponectin/AdipoR1/AMPK axis. Suggesting a novel mechanism in the hypothalamus by which TZDs increase BW.
Aims/hypothesis
We determined the contribution to insulin resistance of the PH domain leucine-rich repeat protein phosphatase (PHLPP), which dephosphorylates Akt at Ser473, inhibiting its activity. ...We measured the abundance of PHLPP in fat and skeletal muscle from obese participants. To study the effect of PHLPP on insulin signalling,
PHLPP
(also known as
PHLPP1
) was overexpressed in HepG2 and L6 cells.
Methods
Subcutaneous fat samples were obtained from 82 morbidly obese and ten non-obese participants. Skeletal muscle samples were obtained from 12 obese and eight non-obese participants. Quantification of PHLPP-1 in human tissues was performed by immunoblotting. The functional consequences of recombinant
PHLPP1
overexpression in hepatoma HepG2 cells and L6 myoblasts were investigated.
Results
Of the 82 obese participants, 31 had normal fasting glucose, 33 impaired fasting glucose and 18 type 2 diabetes. PHLPP-1 abundance was twofold higher in the three obese groups than in non-obese participants (
p
= 0.004). No differences were observed between obese participants with normal fasting glucose, impaired fasting glucose or type 2 diabetes. PHLPP-1 abundance was correlated with basal Akt Ser473 phosphorylation (
r
= −0.48;
p
= 0.001), BMI (
r
= 0.44;
p
< 0.0001), insulin (
r
= 0.35;
p
< 0.0001) and HOMA (
r
= 0.38;
p
< 0.0001). PHLPP-1 abundance was twofold higher in the skeletal muscle of 12 obese participants than in that of eight non-obese participants (
p
< 0.0001). Insulin treatment of HepG2 cells resulted in a dose- and time-dependent upregulation of PHLPP-1. Overexpression of
PHLPP1
in HepG2 cells and L6 myoblasts resulted in impaired insulin signalling involving Akt/glycogen synthase kinase 3, glycogen synthesis and glucose transport.
Conclusions/interpretation
Increased abundance of PHLPP-1, production of which is regulated by insulin, may represent a new molecular defect in insulin-resistant states such as obesity.
Backgrounds/Objectives:The activity of brown/beige adipose tissue (B/BAT) is inversely proportional to body adiposity. Studies have shown that obese subjects submitted to distinct approaches aimed at ...reducing body mass present an increase of B/BAT activation. However, it is unknown if this beneficial effect of body mass reduction applies to patients with type 2 diabetes mellitus. In this study, we evaluated the impact of massive body mass reduction obtained as a consequence of bariatric surgery in the cold-induced activation of B/BAT in obese non-diabetic (OND) and obese diabetic (OD) subjects.
This is an observational study. Fourteen OND, 14 OD and 11 subjects were included in the study. All obese subjects were submitted to Roux-in-Y gastric bypass and measurements were performed before and 8 months after surgery. B/BAT was evaluated by (
F)-FDG-PET/CT scan and determination of signature transcript expression in specimens obtained in biopsies.
Before surgery, mean B/BAT activity and the expression of signature transcripts were similar between OND and OD groups. Eight months after surgery, body mass reduction was similar between the obese groups. Nevertheless, the activity of B/BAT was increased in OND and unchanged in OD subjects. This effect was correlated with a more pronounced improvement of insulin resistance, as evaluated by the hyperinsulinemic, euglycemic clamp, in OND subjects as compared with OD subjects.
Body mass reduction has a more efficient effect to induce the activation of B/BAT in non-diabetic than in diabetic subjects. This effect is accompanied by more pronounced insulin sensitivity and serine 473 phosphorylation of Akt in B/BAT of non-diabetic than in diabetic subjects.
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