Type 2 diabetes (T2D) is characterized by insulin resistance and defective insulin secretion. Previously, we found that rats fed soft pellets (SPs) on a 3-hour restricted schedule over 14 weeks demonstrated glucose intolerance and insulin resistance with disruption of insulin signaling.

To determine (1) the time required for an SP diet to induce insulin resistance, and (2) whether the metabolic derangements in rats fed SPs can be reversed by changing to a standard control diet.

We performed glucose tolerance tests and calculated the homeostasis model assessment of insulin resistance (HOMA-IR) to evaluate the insulinemic response to glucose and assess insulin resistance in non-obese male rats fed control pellets (CPs) or SPs on a 3-hour restricted schedule (10:00 to 13:00) for 4 and 9 weeks. At 11 weeks, we switched half of the insulin-resistant SP group to CPs (soft-to-control pellets [SCPs]) and after an additional 11 weeks, evaluated changes in glucose and lipid metabolism across the three groups.

The glucose tolerance test results in the SP and CP rats did not differ at 4 or 9 weeks. The insulin levels in the SP group were higher than in the CP group at both time points (P < 0.05). The HOMA-IR was significantly higher in the SP rats at 9 weeks compared with the controls (P < 0.05). At 22 weeks, the HOMA-IR, blood glucose levels at 30 minutes after initiating feeding, hepatic glucose metabolism, and lipid synthesis in the rats fed SPs continuously were significantly greater than in those fed CPs (P < 0.05); however, these values in the SCP rats did not differ from those in the CP rats.

A continuous diet of soft textured, readily absorbable food may be an important and reversible underlying driver in T2D pathogenesis.

The rising prevalence of metabolic diseases calls for innovative treatments. Peptide-based drugs have transformed the management of conditions such as obesity and type 2 diabetes. Yet, challenges persist in oral delivery of these peptides. This review explores the potential of 'advanced microbiome therapeutics' (AMTs), which involve engineered microbes for delivery of peptides in situ, thereby enhancing their bioavailability. Preclinical work on AMTs has shown promise in treating animal models of metabolic diseases, including obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease. Outstanding challenges toward realizing the potential of AMTs involve improving peptide expression, ensuring predictable colonization control, enhancing stability, and managing safety and biocontainment concerns. Still, AMTs have potential for revolutionizing the treatment of metabolic diseases, potentially offering dynamic and personalized novel therapeutic approaches.

Highly prevalent comorbidities associated with metabolic syndrome, such as abdominal obesity, nonalcoholic fatty liver disease (NAFLD) and insulin-resistance/Type 2 diabetes (IR/T2D) share alterations in gut microbiota composition as a potential triggering factor. Recent studies put the attention in the potential usage of postbiotics (inactivated probiotics) on these metabolic alterations. This review summarizes the current evidence regarding the efficacy of postbiotic administration in both, preclinical and clinical studies, for the management of obesity, NAFLD and IR/T2D. Data from preclinical studies (rodents) suggest that postbiotic administration effectively prevents obesity, whereas clinical studies corroborate these benefits also in overweight/obese subjects receiving inactivated bacteria. As for NAFLD, although preclinical studies indicate that postbiotic administration improves different liver markers, no data obtained in humans have been published so far since all the studies are ongoing clinical trials. Finally, while the administration of inactivated bacteria demonstrated to be a promising approach for the management of IR/T2D in rodents, data from clinical trials indicates that in humans, this approach is more effective on IR than in T2D. In conclusion, the available scientific data indicate that postbiotic administration not only is safer, but also as effective as probiotic administration for the management of obesity associated prevalent metabolic alterations.

This study aimed to systematically review longitudinal studies examining associations between the incidence of type 2 diabetes mellitus (T2DM) and built environmental factors. This review adhered to the 2020 PRISMA guidelines. Longitudinal studies examining associations between T2DM incidence and built environmental features were eligible. Built environment constructs corresponded to the following themes: 1) Walkability - factors such as sidewalks/footpaths, crosswalks, parks, and density of businesses and services; (2) Green/open space - size, greenness, and type of available public outdoor spaces; (3) Food environment - ratio of healthful food outlets (e.g., greengrocers, butchers, supermarkets, and health food shops) to unhealthful food outlets (e.g., fast-food outlets, sweet food retailers, and convenience stores). Five databases (e.g., Medline) were searched from inception until July 2023. Qualitative and quantitative synthesis were used to summarise key findings, including a meta-analysis of adjusted Hazard Ratios (aHR). Of 3,343 articles, 16 longitudinal studies from seven countries, published between 2015 and 2023, involving 13,403,902 baseline participants (median of 83,898), were included. In four of the five studies, unhealthful food environment was significantly associated with higher incident T2DM. Five of seven greenspace studies and two of four walkability studies showed that greater greenery and greater walkability were statistically significantly associated with lesser incident T2DM. In pooled analyses, greater T2DM incidence was associated with unhealthful relative to healthful food environments (pooled HR: 1.21; 95% CI: 1.04, 1.42), and T2DM incidence was inversely associated with green/open space environments (pooled HR: 0.82; 95% CI: 0.74, 0.92). Greater walkability was associated with a slight 2% lesser incidence of T2DM (pooled HR: 0.98; 95% CI: 0.98, 0.99). This review underscores consistency in the nature of associations between built environment features related to T2DM. We observed statistically significant inverse or "protective" associations between T2DM and walkability and healthful food environments. These results support calls for policies and guidelines that promote healthful food environments and walkability.

Olfactory dysfunction, influenced by factors such as aging and environmental stress, is linked to various neurological disorders. The olfactory bulb's connections to brain areas like the hypothalamus, piriform cortex, entorhinal cortex, and limbic system make olfactory dysfunction a contributor to a range of neuropathological conditions. Recent research has underscored that olfactory deficits are prevalent in individuals with both metabolic syndrome and dementia. These systemic metabolic alterations correlate with olfactory impairments, potentially affecting brain regions associated with the olfactory bulb. In cases of metabolic syndrome, phenomena such as insulin resistance and disrupted glucose metabolism may result in compromised olfactory function, leading to multiple neurological issues. This review synthesizes key findings on the interplay between metabolic-induced olfactory dysfunction and neuropathology. It emphasizes the critical role of olfactory assessment in diagnosing and managing neurological diseases related to metabolic syndrome.

Metabolic diseases, notably obesity and type 2 diabetes (T2D), have reached alarming proportions and constitute a significant global health challenge, emphasizing the urgent need for effective preventive and therapeutic strategies. In contrast, exercise training emerges as a potent intervention, exerting numerous positive effects on metabolic health through adaptations to the metabolic tissues. Here, we reviewed the major features of our current understanding with respect to the intricate interplay between metabolic diseases and key metabolic tissues, including adipose tissue, skeletal muscle, and liver, describing some of the main underlying mechanisms driving pathogenesis, as well as the role of exercise to combat and treat obesity and metabolic disease.

Obesity is reaching epidemic proportions with 51% of the population expected to be obese by 2030. Recently, polyphenols have been highlighted as an effective approach to managing obesity and associated risks. Polyphenols are a large class of bioactive plant compounds classified into two major categories: flavonoids which are distinguished by the fundamental C6-C3-C6 skeleton and non-flavonoids.

This systematic review evaluated the effect of different polyphenol sources in overweight and obese people with and without type 2 diabetes. The primary outcome was lipid profile and the secondary outcomes were blood glucose, HbA1c (%), HOMA-IR, weight, and body mass index.

A search was undertaken in PubMed, Web of Science, Medline, and Wiley for randomized control trials that assessed different sources of polyphenols in overweight and obese people with or without type 2 diabetes. The quality of the included studies was assessed using the National Heart, Lung, and Blood Institute Quality Assessment Tool.

The search yielded 935 studies, of which six randomized control trials met the inclusion criteria. Five studies found no significant difference in lipid profile between the control and intervention groups in triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol. However, one study showed significant differences in triglycerides (p = 0.04) and HDL cholesterol (p = 0.05) between the two groups with no significant difference in total cholesterol and LDL cholesterol. There were no significant changes in blood glucose observed in the included studies, with only two studies reporting a significant difference in A1c between the groups. Four studies found no difference in HOMA-IR, while one study showed a significant decrease in HOMA-IR in the intervention group compared to the control group. Three studies reported no difference in BMI or weight between the two groups.

The data associated with the specific health benefits of polyphenols and their sources in people with overweight, obese, and type 2 diabetes are still limited, so further research is required to support their use and prove their benefits.

An understanding of factors that affect the foveal avascular zone (FAZ) in healthy eyes may aid in the early identification of patients at risk of retinal pathology, thereby allowing better management and preventive measures to be implemented.

The size and shape of the FAZ can change due to retinal diseases associated with oxidative stress, including diabetic retinopathy, glaucoma, and macular degeneration. This study aimed to assess the relationship, if any, between factors that may affect the superficial FAZ (i.e., vessel density, vessel perfusion, overweight/obesity) and possible links with macular pigment optical density in young, healthy participants.

One hundred thirty-nine participants aged 18 to 35 years were recruited to this cross-sectional study. The superficial FAZ area, foveal vascularity, and central macular thickness (CMT) were assessed using the Cirrus 5000. Health parameters, body mass index, trunk fat %, and macular pigment were analyzed to determine possible associations with the superficial FAZ.

Mean FAZ area was 0.23 ± 0.08 mm2. Females had a significantly larger mean FAZ area than males (p=0.002). The FAZ area was positively correlated with body mass index (Pearson's r = 0.189, p=0.026). Significant correlates of the FAZ area in the multivariate model included vessel perfusion (central), CMT, and trunk fat %, collectively explaining 65.1% of the overall variability.

Study findings suggest that reduced vessel perfusion, thinner CMT, and higher trunk fat % are plausible predictors of a larger FAZ area in healthy Caucasian adults. Low macular pigment optical density was, however, not associated with increased FAZ size in young healthy eyes. Noninvasive optical coherence tomography angiography testing, in association with these predictors, may aid in the early detection and monitoring of retinal diseases associated with oxidative stress.

The authors sought to correlate the complex sequel of obesity with various parameters known to develop metabolic syndrome viz. insulin resistance, dyslipidemia, hypertension etc., as these anomalies are linked to vascular atherosclerosis and outbreak of cardiovascular and cerebrovascular diseases.  A comprehensive online survey using MEDLINE, Scopus, PubMed and Google Scholar was conducted for relevant journals from 1970 till present time (2023) with key search terms like: 'obesity', 'leptin', type-2 diabetes', 'atherosclerosis', 'cardiovascular and cerebrovascular diseases'. The findings of the reports were compared and correlated. The information was then collated for developing this review. Reports showed that in human obesity, hyper-leptinemia could induce hyperglycemia, which in turn templates hypercholesterolemia. Persisting hypercholesterolemia over a period of time may en-route atherosclerosis in blood vessels. Thus obesity has been considered as a template for originating hyperglycemia, hypercholesterolemia and outbreak of vascular atherogenesis or in other words, obesity in long run can trigger atherosclerosis and its related disorders e.g. heart attack and stroke. Literature survey shows that primarily, co-morbidities of human obesity start with leptin and insulin resistance and then multiplies with metabolic irregularities to an extreme that results in pathogenesis of heart attack and stroke. Atherosclerosis associated cardiovascular and cerebrovascular events are independent risks of obese subjects and particularly in the cases of persisting obesity.

Help public health decision-making requires a better understanding of the dynamics of obesity and type 2 diabetes and an assessement of different strategies to decrease their burdens.

Based on 97,848 individual data, collected in the French Health, Health Care and Insurance Survey over 1998-2014, a Markov model was developed to describe the progression of being overweight to obesity, and the onset of type 2 diabetes. This model traces and predicts 2022-2027 burdens of obesity and type 2 diabetes, and lifetime risk of diabetes, according to different scenarios aiming at minimum to stabilize obesity at 5 years.

Estimated risks of type 2 diabetes increase from 0.09% (normal weight) to 1.56% (obesity II-III). Compared to the before 1995 period, progression risks are estimated to have nearly doubled for obesity and tripled for type 2 diabetes. Consequently, over 2022-2027, the prevalence of obesity and type 2 diabetes will continue to increase from 17.3% to 18.2% and from 7.3% to 8.1%, respectively. Scenarios statibilizing obesity would require a 22%-decrease in the probability of move up (scenario 1) or a 33%-increase in the probability of move down (scenario 2) one BMI class. However, this stabilization will not affect the increase of diabetes prevalence whereas lifetime risk of diabetes would decrease (30.9% to 27.0%). Combining both scenarios would decrease obesity by 9.9%. Only the prevalence of obesity III shows early change able to predict the outcome of a strategy: for example, 6.7%-decrease at one year, 13.3%-decrease at two years with scenario 1 stabilizing obesity at 5 years.

Prevalences of obesity and type 2 diabetes will still increase over the next 5 years. Stabilizing obesity may decrease lifetime risks of type 2 diabetes without affecting its short-term prevalence. Our study highlights that, to early assess the effectiveness of their program, public health policy makers should rely on the change in prevalence of obesity III.

Obesity, a multifactorial, relapsing chronic disease, serves as a gateway to a spectrum of metabolic, cardiovascular, mechanical and mental health problems. Over the last few decades, the global prevalence of obesity has surged nearly threefold, mirroring the escalating rates of type 2 diabetes mellitus (T2DM). This parallel trajectory strongly suggests a cause-and-effect relationship between obesity and T2DM. Extensive research indicates that even modest weight gain elevates the risk of T2DM, favoring the notion of obesity being a root cause. This perspective finds robust support in numerous studies demonstrating the preventive effects of obesity management on the onset of T2DM. Beyond prevention, obesity management has been shown to enhance remission in individuals with T2DM and to decrease microvascular complications, cardiovascular risk factors, renal failure and heart failure. This evidence underpins the urgent need for global initiatives aimed at addressing obesity management as a key strategy in the prevention and management of T2DM and its complications.

We aimed to investigate weight change in patients with new-onset type 2 diabetes mellitus and the association of weight loss on diabetes remission in Korean adults.

We used the health examination database of the Korean National Health Insurance Service. Patients diagnosed with type 2 diabetes mellitus from 2009 to 2012 were enrolled and followed to 2017. The baseline body weight was measured at the health examination closest to the time the patient was enrolled, and the change was calculated by examining the weight measured at the subsequent examination within 2 years. Remission was defined as fasting blood glucose less than 126 mg/dl at two or more consecutive health examinations after stopping medication.

In total, 114, 874 patients with new-onset type 2 diabetes mellitus were analysed. Of these, 23 156 (20.2%) lost more than 5% of their body weight, and 2429 (2.1%) achieved remission. The adjusted odds ratio for remission in the weight loss group was 2.56 (95% confidence interval 2.35-2.79) compared with the group with stable body weight. Sensitivity analysis according to the degree of weight change showed that the greater weight loss, the higher the likelihood of remission. In the subgroup analysis, the effects of weight loss on remission were significantly greater in subgroups of age <65 years, male sex and body mass index >25.

Weight loss within the first 2 years of treating type 2 diabetes mellitus was associated with diabetes remission. Physicians should pay more attention to weight management in new-onset type 2 diabetes mellitus, particularly for young and obese individuals.

Obesity is a global health concern and a chronic disease that is accompanied by excessive fat storage in adipose and nonadipose tissues. An increase in the body-mass index (BMI) is directly proportional to the 2- to 3.9-fold increase in all-cause mortality in obesity. If left untreated for a longer period, obesity-related metabolic, cardiovascular, inflammatory, and malignant diseases reduce life expectancy. Currently, most of the anti-obesity drugs have failed and fallen into disrepute, either due to their ineffectiveness or adverse effects. In this review, depending on their enhanced pharmacokinetic and biodistribution profiles, whether nanocarriers alter the basic properties and bioactivity of anti-obesity drugs used in clinical practice are debated. First, nanocarriers can improve the safety of still-used anti-obesity drugs by lowering their systemic toxicity through increasing targeting efficacy and preventing drug carrier toxicity. Second, when the micro-ribonucleic acids (miRNAs), which are aberrantly expressed in obesity and obesity-related diseases, are encapsulated into nanoparticles, they are effective in multiple obesity-related metabolic pathways and gene networks. Finally, a synergistic anti-obesity effect with low dose and low toxicity can be obtained with the combinatory therapy applied by encapsulating the anti-obesity drug and gene in the same nanocarrier delivery vehicle.

Polygenic risk scores (PRSs) have been studied for predicting human diseases, and various methods for PRS calculation have been developed. Most PRS studies to date have focused on European ancestry, and the performance of PRS has not been sufficiently assessed in East Asia. Herein, we evaluated the predictive performance of PRSs for East Asian populations under various conditions. Simulation studies using data from the Korean cohort, Health Examinees (HEXA), demonstrated that SBayesRC and PRS-CS outperformed other PRS methods (lassosum, LDpred-funct, and PRSice) in high fixed heritability (0.3 and 0.7). In addition, we generated PRSs using real-world data from HEXA for ten diseases: asthma, breast cancer, cataract, coronary artery disease, gastric cancer, glaucoma, hyperthyroidism, hypothyroidism, osteoporosis, and type 2 diabetes (T2D). We utilized the five previous PRS methods and genome-wide association study (GWAS) data from two biobank-scale datasets [European (UK Biobank) and East Asian (BioBank Japan) ancestry]. Additionally, we employed PRS-CSx, a PRS method that combines GWAS data from both ancestries, to generate a total of 110 PRS for ten diseases. Similar to the simulation results, SBayesRC showed better predictive performance for disease risk than the other methods. Furthermore, the East Asian GWAS data outperformed those from European ancestry for breast cancer, cataract, gastric cancer, and T2D, but neither of the two GWAS ancestries showed a significant advantage on PRS performance for the remaining six diseases. Based on simulation data and real data studies, it is expected that SBayesRC will offer superior performance for East Asian populations, and PRS generated using GWAS from non-East Asian may also yield good results.

Skin diseases impact significantly on the quality of life and psychology of patients. Obesity has been observed as a risk factor for skin diseases. Skin epidermal barrier dysfunctions are typical manifestations across several dermatological disturbances.

We aim to establish the association between obesity and skin physiology measurements and investigate whether obesity may play a possible causal role on skin barrier dysfunction.

We investigated the relationship of obesity with skin physiology measurements, namely transepidermal water loss (TEWL), skin surface moisture and skin pH in an Asian population cohort (n = 9990). To assess for a possible causal association between body mass index (BMI) and skin physiology measurements, we performed Mendelian Randomization (MR), along with subsequent additional analyses to assess the potential causal impact of known socioeconomic and comorbidities of obesity on TEWL.

Every 1 kg/m2 increase in BMI was associated with a 0.221% (95%CI: 0.144-0.298) increase in TEWL (P = 2.82E-08), a 0.336% (95%CI: 0.148-0.524) decrease in skin moisture (P = 4.66E-04) and a 0.184% (95%CI: 0.144-0.224) decrease in pH (P = 1.36E-19), adjusting for age, gender, and ethnicity. Relationships for both TEWL and pH with BMI remained strong (Beta 0.354; 95%CI: 0.189-0.520 and Beta -0.170; 95%CI: -0.253 to -0.087, respectively) even after adjusting for known confounders, with MR experiments further supporting BMI's possible causal relationship with TEWL. Based on additional MR performed, none of the socioeconomic and comorbidities of obesity investigated are likely to have possible causal relationships with TEWL.

We establish strong association of BMI with TEWL and skin pH, with MR results suggestive of a possible causal relationship of obesity with TEWL. It emphasizes the potential impact of obesity on skin barrier function and therefore opportunity for primary prevention.

Type 2 diabetes (T2DM) and obesity represent major global health burdens and economic costs to healthcare systems. T2DM management is challenging due to multiple comorbidities and limited drug efficacy. Bariatric surgery has emerged as an effective treatment approach. A 65-year-old man with refractory obesity (BMI > 35 kg/m2) and poorly controlled T2DM underwent gastric bypass surgery in 2018. Prior to surgery, medication noncompliance and dietary measures failed to achieve adequate glycemic control or weight loss. Postoperatively, the patient lost 20 kg and achieved improved T2DM control (HbA1C reduction), allowing complete cessation of diabetic medications. The patient's case demonstrates bariatric surgery's potential to significantly alter the clinical course of obesity and T2DM versus standard care. National guidelines outline eligibility criteria for bariatric referral; however, utilization rates remain low (<1%) despite over two million eligible individuals in the United Kingdom. Improved access could reduce disease burden and healthcare costs from diabetes complications over the long term. This case report provides a real-world example supporting bariatric surgery as an effective intervention for appropriately selected patients with obesity and uncontrolled T2DM, with the potential to improve clinical outcomes and lower costs associated with diabetes management.

Several large observational prospective studies have reported a protection by the traditional Mediterranean diet against type 2 diabetes, but none of them used yearly repeated measures of dietary intake. Repeated measurements of dietary intake are able to improve subject classification and to increase the quality of the assessed relationships in nutritional epidemiology. Beyond observational studies, randomized trials provide stronger causal evidence. In the context of a randomized trial of primary cardiovascular prevention, we assessed type 2 diabetes incidence according to yearly repeated measures of compliance with a nutritional intervention based on the traditional Mediterranean diet.

PREDIMED (''PREvención con DIeta MEDiterránea'') was a Spanish trial including 7447 men and women at high cardiovascular risk. We assessed 3541 participants initially free of diabetes and originally randomized to 1 of 3 diets: low-fat diet (n = 1147, control group), Mediterranean diet supplemented with extra virgin olive (n = 1154) or Mediterranean diet supplemented with mixed nuts (n = 1240). As exposure we used actual adherence to Mediterranean diet (cumulative average), yearly assessed with the Mediterranean Diet Adherence Screener (scoring 0 to 14 points), and repeated up to 8 times (baseline and 7 consecutive follow-up years). This score was categorized into four groups: < 8, 8-< 10, 10- < 12, and 12-14 points. The outcome was new-onset type 2 diabetes.

Multivariable-adjusted hazard ratios from time-varying Cox models were 0.80 (95% confidence interval, 0.70-0.92) per + 2 points in Mediterranean Diet Adherence Screener (linear trend p = .001), and 0.46 (0.25-0.83) for the highest (12-14 points) versus the lowest (< 8) adherence. This inverse association was maintained after additionally adjusting for the randomized arm. Age- and sex-adjusted analysis of a validated plasma metabolomic signature of the Mediterranean Diet Adherence Screener (constituted of 67 metabolites) in a subset of 889 participants also supported these results.

Dietary intervention trials should quantify actual dietary adherence throughout the trial period to enhance the benefits and to assist results interpretation. A rapid dietary assessment tool, yearly repeated as a screener, was able to capture a strong inverse linear relationship between Mediterranean diet and type 2 diabetes. Trial registration ISRCTN35739639.

Diabetes in pregnancy is a major risk factor for adverse perinatal outcomes such as congenital anomalies, hypertensive disorders of pregnancy (HDP), and macrosomia. For the mechanism of onset of type 1 and type 2 diabetes are different, we focused on the difference in perinatal outcomes between the type 1 and type 2 diabetes groups.

We retrospectively reviewed 22 pregnancies with type 1 diabetes and 15 pregnancies with type 2 diabetes, who were managed in our single center, with regard to maternal diabetes conditions during pregnancy and neonatal birthweight and blood glucose level. Furthermore, we checked the effect of continuous glucose monitoring and continuous subcutaneous insulin injection in pregnancies with type 1 diabetes.

Type 1 diabetes in pregnancy was less controllable and increased neonatal birth weight and neonatal hypoglycemia within 2 h after birth after neonatal care unit admission. Continuous glucose monitoring and continuous subcutaneous insulin injection that are convenient to use, had a similar effect in the management of type 1 diabetes during pregnancy, compared with conventional diabetes treatment. In contrast, maternal BMI and HDP were increased in women with type 2 diabetes.

In the management of pregnancy with diabetes, we should pay attention to the difference in pregnancy prognosis between type 1 and type 2 diabetes.

Overstimulation of pancreatic β-cells can lead to dysfunction and death, prior to the clinical manifestations of type 2 diabetes (T2D). The excessive consumption of carbohydrates induces metabolic alterations that can affect the functions of the β-cells and cause their death. We analyzed the role of p53 in pancreatic β cell death in carbohydrate-supplemented Sprague Dawley rats. For four months, the animals received drinking water containing either 40% sucrose or 40% fructose. The glucose tolerance test was performed at week 15. Apoptosis was assessed with the TUNEL assay (TdT-mediated dUTP-nick end-labeling). Bax, p53, and insulin were assessed by Western blotting, immunofluorescence, and real-time quantitative PCR. Insulin, triacylglycerol, and serum glucose and fatty acids in pancreatic tissue were measured. Carbohydrate consumption promotes apoptosis and mobilization of p53 from the cytosol to rat pancreatic β-cell mitochondria before blood glucose rises. An increase in p53, miR-34a, and Bax mRNA was also detected (P < 0.001) in the sucrose group. As well as hypertriglyceridemia, hyperinsulinemia, glucose intolerance, insulin resistance, visceral fat accumulation, and increased pancreatic fatty acids in the sucrose group. Carbohydrate consumption increases p53 and its mobilization into β-cell mitochondria and coincides with the increased rate of apoptosis, which occurs before serum glucose levels rise.

In many diabetic patients, spermatogenesis complications are frequent causing infertility problems. This study aimed to demonstrate the effect of Forskolin on male reproductive dysfunction caused by type 2 diabetes.

In this experimental study, type 2 diabetes was induced by a high-fat diet (HFD) for one month and then a low single dose injection (35 mg/kg) of streptozotocin (STZ) in Wistar rats. After 72 hours, rats with more than 200 mg/dl of blood glucose were considered type 2 diabetic rats. Forty rats (200-250 g) were divided into four groups (n=10) including group 1 (G1): rats with normal diet and buffer citrate (STZ solvent) injection, group 2 (G2): control type 2 diabetic rats with HFD and STZ injection, group 3 (G3): type 2 diabetic rats received phosphate buffer saline (PBS) as Forskolin solvent, and group 4 (G4): Forskolin treated diabetic rats (10 mg/kg) for 1 month.

In comparison to control group, in diabetic groups (G2 and G3) some parameters are increased significantly: The blood glucose (P=0.00078), testicular malondialdehyde (MDA) level and body weight (P=0.00009) and Bax gene expression (P=0.00007). Unlike, some parameters are decreased significantly: The serum level of testosterone (P=0.0009), testicular superoxide dismutase (SOD, P=0.00007) and glutathione peroxidase (GPX) levels (P=0.00008), sperm concentration (P=0.00008), motility (P=0.00009), normal morphological sperm (P=0.00008) and Bcl-2 gene expression (P=0.00009). However, in Forskolin treated group (G4) the parameters stayed close to control values that was significantly (P=0.00007) higher than in G2 and G3 groups. Therefore, treatment with Forskolin significantly improved these abnormal changes in Forskolin-treated group.

Our study demonstrates that Forskolin is an effective antidiabetic agent, which significantly improves sperm concentration, testosterone levels, and antioxidant activity in diabetic rats.

Obese females are more likely to suffer from depression and are also more likely to be resistant to current medications. This study examined the potential antidepressant-like effects of 1,4-dihydroxy-2-napthoic acid (DHNA), a selective aryl hydrocarbon receptor modulator (SAhRM), in obese female mice.

Obesity was established by feeding C57BL/6N female mice a high fat diet (HFD) for 9-10 weeks. Subsequently, mice were subjected to unpredictable chronic mild stress (UCMS) or remained unstressed. Daily administration of vehicle or 20 mg/kg DHNA began three weeks prior or on the third week of UCMS. Mice were examined for depression-like behaviors (sucrose preference, forced swim test (FST), splash and tape groom tests), anxiety (open-field test, light/dark test, novelty-induced hypophagia), and cognition (object location recognition, novel object recognition, Morris water maze).

UCMS did not alter, and DHNA slightly increased, weight gain in HFD-fed females. HFD decreased sucrose preference, increased FST immobility time, but did not alter splash and tape tests' grooming time. UCMS did not have additional effects on sucrose preference. UCMS further increased FST immobility time and decreased splash and tape tests' grooming time; these effects were prevented and reversed by DHNA treatment. HFD did not affect behaviors in the cognitive tests. UCMS impaired spatial learning; this effect was not prevented nor reversed by DHNA.

DHNA protected against UCMS-induced depression-like behaviors in HFD-fed female mice. DHNA neither improved nor worsened UCMS-induced impairment of spatial learning. Our findings indicate that DHNA has high potential to act as an antidepressant in obese females.

This network meta-analysis aimed to compare the effects of bariatric surgery, novel glucose-lowering agents (SGLT2i, GLP1RA, DPP4i), and insulin for patients with type 2 diabetes mellitus (T2DM) and obesity.

Four databases were searched from inception to April 2023 to identify randomized controlled trials (RCTs) comparing bariatric surgery, SGLT2i, GLP1RA, DPP4i, insulin, and/or placebo/usual care among patients with T2DM and obesity in the achievement of HbA1c < 7.0 per cent within one year, and 12-month changes in HbA1c and body weight.

A total of 376 eligible RCTs (149 824 patients) were analysed. Bariatric surgery had significantly higher rates of achieving HbA1c < 7.0 per cent than SGLT2i (RR = 2.46, 95 per cent c.i. = 1.28, 4.92), DPP4i (RR = 2.59, 95 per cent c.i. = 1.36, 5.13), insulin (RR = 2.27, 95 per cent c.i. = 1.18, 4.58) and placebo/usual care (RR = 4.02, 95 per cent c.i. = 2.13, 7.93), but had no statistically significant difference from GLP1RA (RR = 1.73, 95 per cent c.i. = 0.91, 3.44), regardless of oral (RR = 1.33, 95 per cent c.i. = 0.66, 2.79) or injectable (RR = 1.75, 95 per cent c.i. = 0.92, 3.45) administration. Significantly more GLP1RA patients achieved HbA1c < 7.0 per cent than other non-surgical treatments. Bariatric surgery had the greatest reductions in HbA1c (∼1 per cent more) and body weight (∼15 kg more) at 12 months. Among novel glucose-lowering medications, GLP1RA was associated with greater reductions in HbA1c than SGLT2i (-0.39 per cent, 95 per cent c.i. = -0.55, -0.22) and DPP4i (-0.51 per cent, 95 per cent c.i. = -0.64, -0.39) at 12 months, while GLP1RA (-1.74 kg, 95 per cent c.i. = -2.48, -1.01) and SGLT2i (-2.23 kg, 95 per cent c.i. = -3.07, -1.39) showed greater reductions in body weight than DPP4i at 12 months.

Bariatric surgery showed superiority in glycaemic control and weight management compared to non-surgical approaches. GLP1RA administered by oral or injectable form demonstrated reduced HbA1c and body weight at 12 months, and was preferable over other non-surgical treatments among patients with T2DM and obesity.

CRD42020201507.

Objective: To examine the associations between social determinants of health (SDOH) and prevalent overweight/obesity status and change in adiposity status among American Indian and Alaska Native (AI/AN) children. Methods: The study sample includes 23,950 AI/AN children 2-11 years of age, who used Indian Health Service (IHS) from 2010 to 2014. Multivariate generalized linear mixed models were used to examine the following: (1) cross-sectional associations between SDOH and prevalent overweight/obesity status and (2) longitudinal associations between SDOH and change in adiposity status over time. Results: Approximately 49% of children had prevalent overweight/obesity status; 18% had overweight status and 31% had obesity status. Prevalent severe obesity status was 20% in 6-11-year olds. In adjusted cross-sectional models, children living in counties with higher levels of poverty had 28% higher odds of prevalent overweight/obesity status. In adjusted longitudinal models, children 2-5 years old living in counties with more children eligible for free or reduced-priced lunch had 15% lower odds for transitioning from normal-weight status to overweight/obesity status. Conclusions: This work contributes to accumulating knowledge that economic instability, especially poverty, appears to play a large role in overweight/obesity status in AI/AN children. Research, clinical practice, and policy decisions should aim to address and eliminate economic instability in childhood.

Overweight and obesity (OO) are significant public health issues, and many elements, including genetics, epigenetics, sedentary lifestyle, comorbid conditions, psychological and environmental pressures, have been linked to OO. More than 2 billion people are presently impacted by the global obesity epidemic, which is still advancing relentlessly. It is a significant public health concern and a major contributor to healthcare costs, because it increases the chance of developing conditions such as heart disease, stroke, type 2 diabetes, and chronic kidney disease (CKD). Using the ranges of 18.5-25 for normality, 25-30 for overweight, and 30 for obesity, BMI (in kg/m²) is used to identify obesity. Vitamin deficiency is one of the causative factors associated with the increasing trend of obesity. Altered vitamin B12 status is a multifactorial trait; changes in B12 status are produced by several single nucleotide polymorphisms (SNPs) in various genes that interact with the environment. They also support coordinated efforts to alter the built environment that is causing the obesity pandemic. Therefore, the present study aimed to evaluate the TCN-2 (776C>G) gene alteration and vitamin B12 levels with respect to different body mass index, as well as associating BMI with other biochemical parameters.

250 individuals were involved in the study; among them, 100 were in the healthy weight range category (BMI: 18.5 to <25 kg/m²), 100 were overweight (BMI: 25.0 to <30 kg/m²), and 50 were obese (BMI: >30 kg/m²). Participants visited during the screening program were subjected to blood pressure measurement, and further peripheral blood samples were drawn from all the participants in plain as well as in EDTA vials for biochemical (lipid profile and vitamin B12 level) analysis and single nucleotide polymorphism studies. Extracted DNA from whole blood collected in EDTA vials using kit protocol was used for genotyping by PCR-RFLP.

The levels of systolic (p < 0.0001) and diastolic blood pressures (p < 0.0001), HDL (p < 0.0001), LDL (p = 0.04), TG (p < 0.0001), cholesterol (p < 0.0001), and VLDL (p < 0.0001) showed significant differences between healthy controls, overweight, and obese groups. The healthy control TCN-2 (776C>G) genotypes were compared with those of overweight and obese participants, and compared to the healthy controls it was observed that overweight (p = 0.01) and obese (p = 0.002) subjects had significant differences in TCN-2 (776C>G) genotypes. For genotypes CG and GG, the odds ratio was 1.61 (0.87-2.95; p = 0.12), and 3.81 (1.47-9.88; p = 0.005) for overweight participants, respectively, and obese participants' calculated odds ratios were 2.49 (1.16-5.36; p = 0.01) and 5.79 (1.93-17.35; p = 0.001), respectively. The relative risk for genotypes CG and GG, was 1.25 (0.93-1.68; p = 0.12), 2.17 (1.12-4.17; p = 0.02) for overweight participants, while the obese participants' calculated relative risks were 1.31 (1.03-1.68; p = 0.01) and 2.02 (1.12-3.65; p = 0.001), respectively. Vitamin B12 levels were analyzed, and it was observed that a significant difference existed among overweight (305.5 pmol/L, p < 0.0001) and obese patients (229 pmol/L, p < 0.0001), respectively, as compared to healthy controls (385.5 pmol/L). Correlation analysis showed a significant association of vitamin B12 level with TG, cholesterol and VLDL; it showed a negative correlation, suggesting that decreases in B12 levels may impact the lipid profile.

The study concluded that a predisposition to the GG genotype of TCN-2 gene polymorphism (776C>G) may increase susceptibility to obesity and the related complications, and higher odds and relative risk for the GG genotype may increase the risk of having obesity and further related complications. Lower vitamin B12 levels were linked with obesity and overweight, and impaired lipid parameters suggested that lower vitamin B12 may impact the altered lipid profile.

To evaluate the impact of a collaborative screening campaign on the prevalence of pre-diabetes and diabetes among the screened population.

A Longitudinal, multicentre study was developed. The Finnish Diabetes Risk Score (FINDRISC) was applied to the eligible population in the participating community pharmacies. Individuals with a FINDRISC score ≥ 15, were eligible to measure their glycated haemoglobin (HbA1c) level at the community pharmacy. If HbA1c≥ 5.7%, participants were referred to a general practitioner (GP) appointment for potential diagnosis of Diabetes.

Out of 909 screened subjects, 405 (44.6%) presented a FINDRISC score ≥ 15. Among the latter, 94 (23.4%) had HbA1c levels that made them eligible for GP referral, of which 35 (37.2%) completed the scheduled appointments. 24 participants were diagnosed with pre-diabetes, and 11 with diabetes. The prevalence was estimated at 2.5% (CI95% 1.6-3.8%) and 7.8% (CI95% 6.2-9.8%) for diabetes and pre-diabetes, respectively.

This collaborative model has proved to be effective in the early detection of diabetes and pre-diabetes. Joint initiatives between health professionals can play a pivotal role in the prevention and diagnosis of diabetes, which may lead to a reduction on the burden to health system and society.

The common C-allele of rs13266634 (c.973C>T or p.Arg325Trp) in SLC30A8 (ZNT8) is associated with increased risk of type 2 diabetes. While previous studies have examined the correlation of the variant with insulin and glucose metabolism, the effects of this variant on insulin and lipid responses after a lipid challenge in humans remain elusive. The goal of this study was to determine whether the C-allele had an impact on an individual's risk to metabolic syndromes in U.S. adults.

We studied the genotypes of rs13266634 in 349 individuals aged between 18 and 65 y with BMI ranging from 18.5 to 45 kg/m². The subjects were evaluated for insulin, glucose, HbA1c, ghrelin, and lipid profiles before and after a high-fat mixed macronutrient tolerance test (MMTT).

We found that the effects of variants rs13266634 on glucose and lipid metabolism were sex-dimorphic, greater impact on males than on females. Insulin incremental area under the curve (AUC) after MMTT was significantly decreased in men with the CC genotype (p < 0.05). Men with the CC genotype also had the lowest fasting non-esterified fatty acid (NEFA) concentrations. On the other hand, the TT genotype was associated with a slower triglyceride removal from the circulation in men after MMTT. The reduced triglyceride removal was also observed in subjects with BMI ≥ 30 carrying either the heterozygous or homozygous T-allele. Nevertheless, the SNP had little effect on fasting or postprandial blood glucose and cholesterol concentrations.

We conclude that the CC genotype negatively affects insulin response after MMTT while the T-allele may negatively influence lipolysis during fasting and postprandial blood triglyceride removal in men and obese subjects, a novel finding in this study.

(1) Background: Type 2 diabetes mellitus (T2DM) and metabolic syndrome are associated with decreased vitamin D. In contrast, high pro-neurotensin (pro-NT) levels are linked with an increased risk of T2DM and cardiovascular disease. We aimed to determine the validity of pro-NT and 25-dihydroxy vitamin D3 levels as predictors for T2DM complications; (2) Methods: One hundred T2DM, and one hundred healthy volunteers participated in this case-control study. Their Pro-NT and 25-hydroxyvitamin D3 levels were evaluated using the ELISA technique; (3) Results: Pro-NT and 25 (OH) vitamin D3 have significant validity and accuracy in T2DM prediction, 84.5%, and 90.5%, respectively (p = 0.001). At a value of <29.5, 25-Hydroxy vitamin D3 showed 88% sensitivity and 93% specificity in predicting T2DM. At a value of >124 Pmol/L, Pro-NT showed 81% sensitivity and 88% specificity in predicting T2DM. At a value of 16.5, 25-Hydroxy vitamin D3 had 78.4% sensitivity and 68.3% specificity in predicting T2DM complications. At a value of >158 pmol/L, Pro-NT predicted T2DM complications with 67.6% sensitivity and 56.0% specificity; (4) Conclusions: 25 (OH) Vit D3 and Pro-NT could identify T2DM patients and predict T2DM complications. More extensive research is required to adequately validate this novel perspective with a large population study.

Eukaryotic Tribbles proteins are pseudoenzymes that regulate multiple aspects of intracellular signalling. Both Drosophila melanogaster and mammalian members of this family of pseudokinases act as negative regulators of insulin signalling. Mammalian tribbles pseudokinase (TRIB) genes have also been linked to insulin resistance and type 2 diabetes mellitus. Type 2 diabetes mellitus is associated with increased body weight, sleep problems and increased long-term mortality. Here, we investigated how manipulating the expression of Tribbles impacts body weight, sleep and mortality. We showed that the overexpression of Drosophila tribbles (trbl) in the fly fat body reduces both body weight and lifespan in adult flies without affecting food intake. Furthermore, it decreases the levels of Drosophila insulin-like peptide 2 (DILP2; ILP2) and increases night-time sleep. The three genes encoding TRIBs of mammals, TRIB1, TRIB2 and TRIB3, show both common and unique features. As the three human TRIB genes share features with Drosophila trbl, we further explored the links between TRIB genetic variants and both body weight and sleep in the human population. We identified associations between the polymorphisms and expression levels of the pseudokinases and markers of body weight and sleep duration. We conclude that Tribbles pseudokinases are involved in the control of body weight, lifespan and sleep.

A low-grade and persistent inflammation, which is the hallmark of obesity, requires the participation of NLRP3 and cell death. During Mycobacterium tuberculosis infection, NLRP3 signaling is important for bacterial killing by macrophages in vitro but was shown to be dispensable for host protection in vivo. We hypothesized that during obesity-tuberculosis (TB) comorbidity, NLRP3 signaling might play a detrimental role by inducing excessive inflammation. We employed a model of high-fat-diet-induced obesity, followed by M. tuberculosis infection in C57BL/6 mice. Obese mice presented increased susceptibility to infection and pulmonary immunopathology compared to lean mice. Using treatment with NLRP3 antagonist and Nlrp3^-/- mice, we showed that NLRP3 signaling promoted cell death, with no effect in bacterial loads. The levels of palmitate were higher in the lungs of obese infected mice compared to lean counterparts, and we observed that this lipid increased M. tuberculosis-induced macrophage death in vitro, which was dependent on NLRP3 and caspase-1. At the chronic phase, although lungs of obese Nlrp3^-/- mice showed an indication of granuloma formation compared to obese wild-type mice, there was no difference in the bacterial load. Our findings indicate that NLRP3 may be a potential target for host-directed therapy to reduce initial and severe inflammation-mediated disease and to treat comorbidity-associated TB. © 2022 The Pathological Society of Great Britain and Ireland.

Objective  Sleep is part of a healthy lifestyle and in adults with diabetes, inadequate sleep is associated with risks of developing complications. The objective was to compare beliefs about healthy sleep habits (HSHs) in adults with versus without diabetes based on the Reasoned Action Approach. Methods  A total of 56 adults with and 98 without diabetes answered open-ended questions regarding their beliefs about: avoiding screen use in bed; having a regular sleep schedule; or avoiding caffeine, alcohol, and cigarettes before bedtime. A qualitative content analysis was used to identify the most important beliefs, similarities, and differences between both groups. Results  Both groups reported that adopting HSHs could improve sleep. Having a regular sleep schedule was perceived to facilitate diabetes management in adults with diabetes. Negative consequences specific to adopting each HSH were identified in both groups. Adopting HSHs was associated with mainly negative emotions (e.g., stress, anxiety, fear) in both groups. Avoiding screen use in bed was associated with anxiety of not knowing blood glucose levels at night in adults with diabetes. Partners, parents, and friends were considered the most important individuals who would approve of adopting HSHs, but they were often perceived as unlikely to adopt HSHs themselves in both groups. Adults with diabetes perceived more barriers to adopting HSHs. Facilitating factors for both groups included removing triggers of unhealthy sleep habits, behavior substitution, using reminders, time management, and social support. Discussion  These beliefs can guide the development of behavioral sleep interventions, including interventions specifically for adults with diabetes.

Type 2 diabetes mellitus (T2D) is a chronic disease characterized by insulin resistance and hyperglycemia. To investigate T2D, genetic and chemical induced hyper-obese rodent models have been experimentally developed. However, establishment of moderate-obese diabetes model will confer diverse opportunities for translational studies. In this study, we found the chemical, GLUTFOURINH® (GFI), induces post-translational degradation of glucose transporter 4 (GLUT4). We aimed to establish novel diabetic model by using GFI.

Low plasma membrane GLUT4 (pmGLUT4) levels by GFI resulted in reduction of intracellular glucose uptake and TG, and increase of intracellular FFA in A204 cells. Likewise, GFI treatment decreased intracellular TG and increased intracellular FFA levels in Hep3B and 3T3-L1 cells. Mice were administered with GFI (16 mg/kg) for short-term (3-day) and long-term (28- and 31-day) to compared with vehicle injection, HFD model, and T2D model, respectively. Short-term and long-term GFI treatments induced hyperglycemia and hyperinsulinemia with low pmGLUT4 levels. Compared to HFD model, long-term GFI with HFD reduced adipose weight and intracellular TG accumulation, but increased plasma FFA. GFI treatment resulted in insulin resistance by showing low QUICKI and high HOMA-IR values, and low insulin response during insulin tolerance test. Additionally, low pmGLUT4 by GFI heightened hyperglycemia, hyperinsulinemia, and insulin resistance compared to T2D model.

In summary, we report GLUT4 degradation by novel chemical (GFI) induces moderate-obese diabetes representing hyperglycemia, insulin resistance and low intracellular lipid accumulation. The GLUT4 degradation by GFI has translational value for studying diseases related to moderate-obese diabetes.

To investigate the impact of pulmonary TB on glycemic status during and after TB treatment, and associations of glycemic trends with antidiabetic therapy and TB outcomes.

Data from two prospective cohort studies of adults in Chennai, India, with pulmonary TB were combined for this analysis. Participants were classified by baseline hemoglobin A1_c (A1C) as having normoglycemia (NG; n = 74), prediabetes (pre-DM; n = 110), or diabetes (DM; n = 244). Repeat A1C measurements were performed at TB treatment months 3 and 6, and then 6 and 12 months after TB treatment completion.

Median A1C at baseline declined after TB treatment initiation in all groups. No baseline NG or pre-DM participants progressed to DM by end of study, while 16.7% of baseline DM participants shifted to pre-DM or NG levels of A1C. In the baseline DM group, rising A1C after the intensive phase of TB treatment was significantly associated with adverse TB outcomes.

Incident TB promotes transient glucose elevation but was not conclusively shown to promote chronic dysglycemia. Rising A1C during and after TB treatment may predict unfavorable treatment response in persons presenting with A1C ≥ 6.5 % at the time of TB diagnosis.

Central obesity is one of the major risk factors for type 2 diabetes mellitus (DM), and the most common complication of DM is diabetic retinopathy. However, the exact relationship between obesity and DR remains unknown. In this study, we evaluate the effect of obesity on DR by comparing the aqueous humor-derived adipokines. For the analysis, 37 DR patients and 29 non-DR-patients participated. To evaluate the obesity of the patients, body mass index (BMI) and waist circumference (WC) were used. By comparing the concentrations of adipokines obtained from the aqueous humor of the two groups, the relationship between DR and adipokines was analyzed. In addition, by analyzing the correlation between obesity and adipokines in patients, the relationship between central obesity and DR was finally confirmed. The WC was significantly higher in patients than in the non-patient group. The concentrations of all adipokines compared in this study were significantly higher in the DR group than in the non-DM group (p < 0.05). Among them, adiponectin, leptin, TNF-α, Factor D (adipsin), lipocalin-2 (NGAL), Serpin E1 (PAI-1), and CXCL8 (IL-8) were confirmed to have a positive correlation with central obesity (defined as WC). These findings suggest that central obesity is strongly associated with the risk of DR.

It is known that people with prediabetes increase their risk of developing type 2 diabetes (T2D), which constitutes a global public health concern, and it is associated with other diseases such as cardiovascular disease.

This study aimed to determine those factors with high influence in the development of T2D once prediabetes has been diagnosed, through a Bayesian network (BN), which can help to prevent T2D. Furthermore, the set of features with the strongest influences on T2D can be determined through the Markov blanket. A BN model for T2D was built from a dataset composed of 12 relevant features of the T2D domain, determining the dependencies and conditional independencies from empirical data in a multivariate context. The structure and parameters were learned with the bnlearn package in R language introducing prior knowledge. The Markov blanket was considered to find those features (variables) which increase the risk of T2D.

The BN model established the different relationships among features (variables). Through inference, a high estimated probability value of T2D was obtained when the body mass index (BMI) was instantiated to obesity value, the glycosylated hemoglobin (HbA1c) to more than 6 value, the fatty liver index (FLI) to more than 60 value, physical activity (PA) to no state, and age to 48-62 state. The features increasing T2D in specific states (warning factors) were ranked.

The feasibility of BNs in epidemiological studies is shown, in particular, when data from T2D risk factors are considered. BNs allow us to order the features which influence the most the development of T2D. The proposed BN model might be used as a general tool for prevention, that is, to improve the prognosis.

This study aimed to identify novel genetic factors that contribute to body surface area (BSA) and explore its relationship with complex traits and diseases.

Based on more than 330,000 European individuals in the UK Biobank, the first large-scale genome-wide association study for BSA was performed. Comprehensive genetic analysis and enrichment analysis were then performed to explore the biological function of the identified loci. The genetic correlations and causal associations between BSA and other anthropometry parameters, early growth indices, and later-life diseases, respectively, were assessed by complex genetic approaches.

Genome-wide association study analysis identified a total of 456 conditionally independent single-nucleotide polymorphism mapping genes with known functions in the regulation of adipogenesis and metabolism and enriched in adipogenesis-related pathways. BSA was highly genetically correlated with obesity phenotypes, and all the studied anthropometry parameters from the UK Biobank were significantly positively associated with BSA. BSA was phenotypically associated with 13 chronic diseases and genetically associated with 6 diseases. Mendelian randomization analyses showed that BSA has a causal effect in increasing the risk of some diseases.

These findings increase understanding of genetic determinants for BSA and its relationship with complex traits and diseases, and BSA could be regarded as a potential obesity trait.

Vascular diseases of the elderly are a topic of enormous interest in clinical practice, as they have great epidemiological significance and lead to ever-increasing healthcare expenditures. The mechanisms underlying these pathologies have been increasingly characterized over the years. It has emerged that endothelial dysfunction and chronic inflammation play a diriment role among the most relevant pathophysiological mechanisms. As one can easily imagine, various processes occur during aging, and several pathways undergo irreversible alterations that can promote the decline and aberrations that trigger the diseases above. Endothelial dysfunction and aging of circulating and resident cells are the main characteristics of the aged organism; they represent the framework within which an enormous array of molecular abnormalities occur and contribute to accelerating and perpetuating the decline of organs and tissues. Recognizing and detailing each of these dysfunctional pathways is helpful for therapeutic purposes, as it allows one to hypothesize the possibility of tailoring interventions to the damaged mechanism and hypothetically limiting the cascade of events that drive the onset of these diseases. With this paper, we have reviewed the scientific literature, analysing the pathophysiological basis of the vascular diseases of the elderly and pausing to reflect on attempts to interrupt the vicious cycle that connotes the diseases of aging, laying the groundwork for therapeutic reasoning and expanding the field of scientific research by moving from a solid foundation.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been observed in several large cardiovascular outcome trials to significantly reduce the incidence of major cardiovascular event (MACE) with type 2 diabetic patients. The clinical trials of GLP-1 RAs, including lixisenatide, exenatide, liraglutide, semaglutide, albiglutide, and dulaglutide, are associated with a significantly 14% lower risk of MACE in patients with T2DM and a history of CV disease, and with a nonsignificantly 6% lower risk in patients without history of CV disease. Some of the interpretation with GLP-1 RA trials suggested the possible role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in primary prevention of cardiovascular diseases in nondiabetic individual, echoed by a recent editorial redefining the role of GLP-1 RAs being beyond glycaemic control. The narrative review provides an in-depth insight into GLP-1 RA use guideline in different countries and regions of the world and examines the safety and concern of GLP-1 RA use. The narrative review draws the comparison of GLP-1 RA use between diabetic and nondiabetic individual in terms of cardiovascular and metabolic benefits and points out the direction of future clinical trials of GLP-1 RAs in nondiabetic individuals. The focus of the review is on GLP-1 RAs' preventive roles in nondiabetic individuals with cardiovascular disease, chronic kidney diseases, obesity, dyslipidaemia, hypertension, nonalcoholic fatty liver diseases, polycystic ovarian syndrome (PCOS), and perioperative complications of bariatric surgery, albeit in small studies and subset analysis of clinical trials of diabetic patients.

Aerobic exercise is well recognised as an effective treatment for people with type 2 diabetes but the optimal amount of aerobic exercise to improve glycaemic control remains to be determined. Thus, the aim of this meta-analysis and meta-regression was to assess the impact of volume and intensity of aerobic exercise on glycaemic control.

Medline, Cochrane, Embase, and Web of Science databases were searched up until 15 December 2020 for the terms "aerobic exercise AND glycaemic control", "type 2 diabetes AND exercise", and "exercise AND glycaemic control AND Type 2 diabetes AND randomised control trial". We included (i) randomised control trials of ≥ 12 weeks, (ii) trials where participants had type 2 diabetes and were aged 18 or over, and (iii) the trial reported HbA1c concentrations pre- and post-intervention. Two reviewers selected studies and extracted data. Data are reported as standardised mean difference (SMD) and publication bias was assessed using funnel plots.

A total of 5364 original titles were identified. Sixteen studies were included in the meta-analysis. Aerobic exercise reduced HbA1c versus control (SMD = 0.56 (95% CI 0.3-0.82), p < 0.001). There were also significant reductions in BMI (SMD = 0.76 (95% CI 0.25-1.27), p < 0.05). There was no dose-response relationship between improvement in HbA1c and the intensity and volume of the intervention (p > 0.05).

Twelve-week or longer aerobic exercise programmes improve glycaemic control and BMI in adults with type 2 diabetes. Longer or more intense interventions appear to confer no additional benefit on HbA1c.

In this review, the authors discuss potential clinical applications for continuous ketone monitoring (CKM) in a broad continuum of clinical settings from pre-hospital care and the emergency department to acute inpatient management and post-discharge follow-up.

Though in its early stages, the concept of a novel continuous ketone sensing technology exerts great potential for use in the detection and hospital management of DKA, namely to overcome diagnostic barriers associated with ketoacidosis in patients with diabetes and obtain real-time BOHB levels, which may be useful in understanding both patients' response to treatment and DKA trajectory. Peri- and intra-operative use of CKM technology can potentially be applied in a number of urgent and elective surgical procedures frequently underwent by patients with diabetes and in the observation of patients during peri-operative fasting. In transitional care management, CKM technology could potentially facilitate patients' safe transition through levels of care, following hospital discharge from a DKA episode. This evaluation of the literature presents the potential advantages of adopting CKM and integrating this technology into the care algorithm of patients at risk for ketoacidosis.

Human Galectin-3 is a 32- to 35-kDa size lectin, mainly comprises a C-terminal carbohydrate recognition binding domain (CRD) and N-terminal domain. It acts as a powerful pro-inflammatory signalling factor, which plays an important role in the activation, chemotaxis, and cytokine release of inflammatory cells. Galectin-3 has also been studied in relation to development of insulin resistance. The levels of galectin-3 have been observed to be associated with both diabetes prevalence and incidence, independent of traditional diabetes risk factors. It is also associated with development of microvascular complications of diabetes mellitus like retinopathy, nephropathy and neuropathy.

Tertiary care hospital-based cross-sectional prospective study. 150 patients selected by simple random sampling and were divided into 3 groups., Group A - Patients of Type 2 Diabetes mellitus without microvascular complications (n=50), Group B - patients of Type 2 diabetes mellitus with microvascular complications (n=50) and Group C - Healthy control (n=50).

Descriptive statistics was performed by calculating mean and standard deviation for the continuous variables. chi-square goodness-to-fit test, Student T test (unpaired) and Analysis of variance (ANOVA) and multivariate analysis were used to compare means. The p-value was taken significant when less than 0.05 (P<0.05) and a confidence interval of 95%.

In group A, B and C majority of patients were between 56-60 years with 34%, 40% and 36% cases, respectively. The mean BMI shows that the Patients with complications had significantly higher BMI than those without complications and controls had significantly lower BMI than patients having diabetes. The data shows statistical significance with deranged biochemical profile in patients with DM with complications as compared to patients without complications and control group. In both groups A and B patients with HbA1c between 9.1-12 had mean serum galectin level (20.2 in group A, 25.9 in group B) significantly higher than patients with HbA1c between 6.5-9 (18.5 in group A and 20.4 in group B). patients with deranged lipid profile had significantly higher serum galectin level in all 3 groups, with cases from group B having higher values than group A. While controls had the lowest value of serum galectin (P value<0.001). There was a highly significant correlation between high serum galectin levels and the incidence of both non-progressive and progressive retinopathy (P value=0.0001). The mean galectin of patients with neuropathy was 28.3 ± 3.1 ng/ml, which was significantly higher than patients from group B without neuropathy (24.5 ± 2.6 ng/ml). The mean serum galectin level of patients with macroalbuminuria was 30.1± 1.3 ng/ml which was significantly higher than those with microalbuminuria having mean galectin level of 22.8 ±4.8 ng/ml. There was a highly significant correlation between high serum galectin levels and the incidence of both micro and macroalbuminuria (P value=0.0001).

This study concludes that elevated serum Galectin-3 levels are associated with diabetes-related chronic inflammatory processing pathway, and closely relates to the severity of diabetes in T2DM both with and without complications. Therefore, Galectin-3 may be helpful in the diagnosis and prognosis of microvascular and macrovascular complications in T2DM patients.