Search Results (57)

Background/Objectives: Insulin-Resistant Normal Weight and Insulin-Sensitive Obesity are atypical cardiometabolic phenotypes whose clinico-biological features, management, and prognosis are a subject of extensive scientific debate. The current study aimed to assess the prevalence of metabolic phenotypes of obesity and to evaluate their association with markers related to diabesity, adipokines profile, and two single nucleotide polymorphisms of CNR1 gene. Methods: We performed a cross-sectional analysis in a random sample of 487 individuals (53.03 ± 13.71 years, 48.3% male) which were classified based on body mass index (</≥25 kg/m²) and insulin resistance (HOMA-IR cut-off value 2.5) as Insulin-Sensitive/Insulin-Resistant Normal Weight (ISNW/IRNW) and Insulin-Sensitive/Insulin-Resistant Obesity (ISO/IRO). Results: The ISO phenotype frequency was 24.2%, with a higher prevalence in the 40–60 years age group (47.0%) and in men (44.9%), while the prevalence of IRNW was 7.0%, predominating in women (61.8%). Participants with IRNW had a more altered glycoregulation profile (fasting and 2 h OGTT blood glucose, prediabetes, and hyperinsulinism), hypercholesterolemia, and adiposity indices (ABSI) than those with ISNW, but comparable to those with IRO. Participants with ISO had a more favorable glycoregulation profile, lipid profile, adipocytokines, and adiposity indices than those with IRO. IRNW had higher odds of being associated with prediabetes (OR 10.75; p < 0.001) than ISNW, while younger age, CUN-BAE, and ABSI were independently associated with both ISO and IRNW phenotypes. Conclusions: The IRNW phenotype should be actively evaluated to intervene on the cardiometabolic risk, while further studies are needed to confirm the sustainability of the favorable cardiometabolic profile of the ISO phenotype. Full article

Obesity and type 2 diabetes are closely linked and often referred to as diabesity. Therapies of diabesity include improving intestinal health and reducing intake of fat and sugars. Diagnosis of diabesity-related metabolic disorders would involve monitoring of glucose and other factors. Nanocellulose, also known as cellulose nanomaterials, is emerging as a potential material for various applications. It has unique properties, such as high surface area, biodegradable, biocompatibility and tunable surface chemistry. In this review, we initially provided a brief description of differently produced nanocellulose and their potential applications in different areas, including therapeutics and diagnostics, by focusing on obesity and diabetes. Then, the uptake, absorption, distribution, metabolism and excretion of nanocellulose were discussed. Further, the mechanisms of nanocellulose in modulating diabesity were summarized by emphasizing the role of gut microbiota. Finally, we discussed gut microbiota-related health effects of nanocellulose, both beneficial and detrimental. It was found that the interactions between nanocellulose and gut were complex, with alterations of microbial composition, metabolic activity, and the immune functions both locally and systemically. There seemed to be many beneficial changes following short-term exposure to nanocellulose (e.g., increased beneficial bacteria and decreased pathogenic ones); however, some of these effects were no longer seen after long-term consumption. Importantly, long-term nanocellulose consumption may be associated with certain detrimental health effects, e.g., malnutrition and its associated neurotoxicity, although additional studies are needed to substantiate such health implications. This information is critical for developing safe and effective nanocellulose derivatives that can be applied in food and medicine as well as to harness the benefits of the gut microbiota. Full article

By 2045, approximately 783.2 million people are projected to be diagnosed with type 2 diabetes mellitus (T2DM). In addition, obesity is expected to affect up to 22% of the world’s population or one in four people. The diabesity epidemic, a worrying trend in which T2DM and obesity co-occur, is becoming increasingly evident and could be the most significant epidemic of non-communicable chronic diseases in human history. The salutogenic pattern of health, which emphasises well-being and resistance resources, could be a promising solution to address this alarming worldwide problem. The salutogenic pattern of health has numerous positive effects on the health of persons with T2DM. These include reducing the risk of it, lowering some biomarkers and laboratory parameters related to its control, and promoting a better lifestyle, ultimately improving the overall quality of life. The salutogenic pattern of health offers an effective and evidence-based approach to address the growing global problem of chronic non-communicable diseases such as T2DM. Integrating this theory into standard modern medical practice has the potential to significantly improve health outcomes and overall patient well-being, making it an important direction for modern medicine. Accordingly, the aim is to explore and analyse the salutogenic pattern of health associated with T2DM in order to prevent it, but also the better management of it. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) and maternal obesity are major global health gestation-related conditions associated with several adverse maternal and neonatal outcomes. GDM is a common gestational metabolic disorder, presented usually during the second or third trimester of pregnancy with maternal hyperglycemia due to insulin intolerance. Maternal obesity, defined as a BMI of a woman during gestation ≥ 30 kg/m², has been associated with maternal complications such as GDM, fetal macrosomia and others. Methods: The presented article is a narrative review. The aim of this study was to review scientific evidence and conduct a comprehensive analysis of GDM and maternal obesity (“diabesity”) and its immediate and late complications for both maternal and fetal/offspring wellbeing. Results: This review highlighted that gestational hyperglycemia results in oxidative and nitrogen stress development and that maternal obesity may have an impact similar to maternal diabetes, as it may cause fetal macrosomia and cardiometabolic complications later in life. Conclusions: Optimal diabetic control is responsible for the prevention of oxidative stress in diabetic pregnancies. Similarly, pregnant women should exercise regularly, receive folic acid supplementation and avoid excess weight gain during pregnancy. Breastfeeding during the first months of life has a positive impact on weight monitoring in infants born to mothers with diabesity and may be crucial in the prevention of obesity and metabolic syndrome later in life. Full article

Background: Diabesity, the coexistence of obesity and type 2 diabetes, is a major public health concern. Shift work and unhealthy lifestyle behaviors may exacerbate its prevalence, particularly in working populations. Objective: This study aims to evaluate the association between sociodemographic characteristics, health behaviors, and shift work and the prevalence of diabesity, using both BMI and the CUN-BAE estimator, in a large cohort of Spanish workers. Methods: This cross-sectional study included 53,053 workers (59.8% men) aged 18–69 years who underwent occupational health examinations. Diabesity was defined as obesity (BMI ≥ 30 kg/m² or high CUN-BAE) plus fasting glucose ≥ 100 mg/dL or prior diagnosis of diabetes. Adherence to the Mediterranean diet was assessed by the MEDAS questionnaire, physical activity by the IPAQ, alcohol intake by standard drink units (UBEs), and socioeconomic class by the CNAE-11 classification. Shift work was defined according to ILO criteria. Logistic regression was used to assess associations, adjusting for potential confounders. Results: Shift work was independently associated with increased odds of diabesity both in men and women. Diabesity prevalence was higher when assessed by CUN-BAE compared with BMI. Age, male sex, lower socioeconomic class, physical inactivity, smoking, poor diet adherence, and alcohol intake were all significantly associated with higher risk. The CUN-BAE index showed superior sensitivity in identifying individuals at risk. Conclusions: Shift work and unhealthy behaviors are key determinants of diabesity among Spanish workers. The use of adiposity estimators beyond BMI, such as CUN-BAE, should be encouraged in occupational health surveillance. Workplace-targeted interventions are urgently needed to address this growing metabolic burden. Full article

Obesity (lipotoxicity) results from a chronic imbalance between energy intake and expenditure. It is strongly associated with type 2 diabetes mellitus (T2DM, glucotoxicity) and considered a major risk factor for the development of metabolic complications. Their convergence constitutes “diabesity”, representing a major challenge for public health worldwide. Limited treatment efficacy highlights the need for novel, multi-targeted therapies. Non-shivering thermogenesis (NST), mediated by brown and beige adipose tissue and skeletal muscle, has emerged as a promising therapy due to its capacity to increase energy expenditure and improve metabolic health. Also, skeletal muscle plays a central role in glucose uptake and lipid oxidation, further highlighting its relevance in diabesity. This review explores current and emerging knowledge on physiological stimuli, including cold exposure, physical activity, and fasting, as well as bioactive ingredients and drugs that stimulate NST in thermogenic tissues. Special emphasis is placed on melatonin as a potential regulator of mitochondrial function and energy balance. The literature search was conducted using MEDLINE and Web of Science. Studies were selected based on scientific relevance, novelty, and mechanistic insight; prioritizing human and high-quality rodent research published in peer-reviewed journals. Evidence shows that multiple interventions enhance NST, leading to improved glucose metabolism, reduced fat accumulation, and increased energy expenditure in humans and/or rodents. Melatonin, in particular, shows promise in modulating thermogenesis through organelle-molecular pathways and mitochondrial protective effects. In conclusion, a multi-target approach through the activation of NST by physiological, nutritional, and pharmacological agents offers an effective and safe treatment for diabesity. Further research is needed to confirm these effects in clinical practice and support their use as effective therapeutic strategies. Full article

Background: Type 2 diabetes (T2D) and overweight or obesity are strongly associated, with a high prevalence of these concomitant conditions contributing significantly to global healthcare costs. Given this burden, there is an urgent need for effective interventions. Mobile health (mHealth) technologies represent a promising strategy to address both conditions simultaneously. Objectives: This systematic review and meta-analysis aimed to evaluate the effectiveness of mHealth-based interventions for the management of adults with T2D and overweight/obesity. Specifically, it assessed the quantitative impact of these interventions on glycosylated hemoglobin (HbA1c), body weight, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. Methods: A systematic search was conducted in PubMed, Web of Science, and Scopus databases from inception to 9 July 2025. The inclusion criteria focused on randomized controlled trials (RCTs) using mHealth interventions in adults with T2D and overweight/obesity, reporting HbA1c or weight as primary or secondary outcomes. The risk of bias was assessed using the Cochrane Risk of Bias tool 2. A total of 13 RCTs met the inclusion criteria. Results: Meta-analysis indicated significant improvements after 6–12 months of intervention in HbA1c (MD −0.23; 95% CI −0.36 to −0.10; p < 0.001; I² = 72%), body weight (MD −2.47 kg; 95% CI −3.69 to −1.24; p < 0.001; I² = 79%), total cholesterol (MD −0.23; 95% CI −0.39 to −0.07; p = 0.004; I² = 0%), and LDL (MD −0.27; 95% CI −0.42 to −0.12; p < 0.001; I² = 0%). Conclusions: mHealth interventions are effective and scalable for managing T2D and obesity, particularly when incorporating wearable technologies to improve adherence. Future research should focus on optimizing personalization, engagement strategies, and long-term implementation. Full article

Obesity and Type 2 Diabetes Mellitus (T2DM) are interrelated chronic conditions whose global prevalence continues to rise, posing significant clinical and socioeconomic challenges. Their pathophysiological intersection—commonly referred to as “diabesity”—is sustained by a complex interplay of mechanisms, including visceral adipose tissue inflammation, macrophage polarization, disrupted insulin signaling, and adipokine imbalance. These processes contribute to chronic low-grade systemic inflammation, impair pancreatic β-cell function, and exacerbate glucose intolerance. This review critically explores the mechanistic connections between obesity and T2DM, with a focus on recent advances in pharmacological therapies—such as GLP-1 receptor agonists, SGLT2 inhibitors, and dual GIP/GLP-1 receptor agonists—alongside evidence-based lifestyle modifications and bariatric procedures. By integrating current translational and clinical findings, we aim to provide a comprehensive perspective to support the development of more effective and individualized treatment strategies for diabesity. Full article

Cancer risk increases by 25 to 250% not only in dysmetabolic obese or overweight people with overt type 2 diabetes but also in individuals with intermediate hyperglycemia (pre-diabetes), with especially pronounced risk of pancreatic or hepatocellular cancer and obesity-related cancers, e.g., colorectal and kidney cancers, bladder cancer in men, and endometrial and breast cancers in women. Cancer may often be present before or upon the diagnosis of diabetes, as there is a common pathogenetic dysmetabolic–inflammatory background with insulin resistance for developing diabetes, cardiorenal disease, and cancer in parallel. The mechanisms involved relate to hyperinsulinemia as a potential carcinogenic priming event with ectopic visceral, hepatic, pancreatic, or renal fat accumulation that subsequently fuel inflammation and lipo-oncogenic signals, causing mitochondrial oxidative stress and deregulation. Moreover, hyperinsulinemia may foster mitogenic MAP kinase-related signaling, which can also occur via IGF1 receptors due to increased free IGF1 levels in obesity. Weight reduction of 10% or more in obese people with diabetes or pre-diabetes, e.g., through intensive lifestyle intervention or bariatric (=metabolic) surgery or through treatment with GLP-1 receptor agonists or metformin, is associated with significantly lower incidence of “diabesity”-associated cancers. In conclusion, there seems to be huge utility in adopting the new “Cardio-Renal-Metabolic-Cancer Syndrome” approach, also looking for cancer at the time of diabetes diagnosis in addition to proactively screening for undiagnosed dysglycemia. Full article

Background/Objectives: Managing type 2 diabetes mellitus (T2DM) and obesity requires a multidimensional, patient-centered approach including nutritional interventions (NIs) and physical activity. Changes in the gut microbiota (GM) have been linked to obesity and the metabolic alterations typical of T2DM and obesity, and they are strongly influenced by diet. However, few studies have evaluated the effects on the GM of a very-low-calorie ketogenic diet (VLCKD) in patients with T2DM, especially in the mid-term and long-term. This longitudinal study is aimed at evaluating the mid-term and long-term impact of the VLCKD and Mediterranean diet (MD) on the GM and on the anthropometric, metabolic, and lifestyle parameters of 11 patients with T2DM and obesity (diabesity). This study extends previously published results evaluating the short-term (three months) impact of these NIs on the same patients. Methods: At baseline, patients were randomly assigned to either a VLCKD (KETO group) or a Mediterranean diet (MEDI group). After two months, the KETO group gradually shifted to a Mediterranean diet (VLCKD-MD), according to current VLCKD guidelines. From the fourth month until the end of the study both groups followed a similar MD. Previous published results showed that VLCKD had a more beneficial impact than MD on several variables for 3 months of NI. In this study, the analyses were extended until six (T6) and twelve months (T12) of NI by comparing data prospectively and against baseline (T0). The GM analysis was performed through next-generation sequencing. Results: Improvements in anthropometric and metabolic parameters were more pronounced in the KETO group at T6, particularly for body mass index (−5.8 vs. −1.7 kg/m²; p = 0.006) and waist circumference (−15.9 vs. −5.2 cm; p = 0.011). At T6, a significant improvement in HbA1c (6.7% vs. 5.5% p = 0.02) and triglyceride (158 vs. 95 mg/dL p = 0.04) values compared to T0 was observed only in the KETO group, which maintained the results achieved at T3. The VLCKD-MD had a more beneficial impact than the MD on the GM phenotype. A substantial positive modulatory effect was observed especially up to the sixth month of the NI in KETO due to the progressive increase in bacterial markers of human health. After the sixth month, most markers of human health decreased, though they were still increased compared with baseline. Among them, the Verrucomicrobiota phylum was identified as the main biomarker in the KETO group, together with its members Verrucomicrobiae, Akkermansiaceae, Verrucomicrobiales, and Akkermansia at T6 compared with baseline. Conclusions: Both dietary approaches ameliorated health status, but VLCKD, in support of the MD, has shown greater improvements on anthropometric and metabolic parameters, as well as on GM profile, especially up to T6 of NI. Full article

Endoplasmic reticulum (ER) stress is a crucial factor in the progression of obesity-related type 2 diabetes (diabesity), contributing to skeletal muscle (SKM) dysfunction, calcium imbalance, metabolic inflexibility, and muscle atrophy. The ER and mitochondria together regulate intracellular calcium levels, and melatonin, a natural compound with antioxidant properties, may alleviate these challenges. Our previous research showed that melatonin raises intracellular calcium and preserves muscle structure by enhancing mitochondrial function in obese diabetic rats. This study further explores melatonin’s potential to reduce ER stress in the vastus lateralis (VL) muscle by modulating the unfolded protein response (UPR) and restoring calcium levels disrupted by diabesity. Five-week-old Zücker diabetic fatty (ZDF) rats and lean littermates of both sexes were divided into control and melatonin-treated groups (10 mg/kg/day for 12 weeks). Flame atomic absorption spectrometry results showed that melatonin restored VL intraorganellar calcium homeostasis, increasing calcium levels in mitochondria and reducing them in the ER by raising the activity and expression of calcium transporters in both sexes of ZDF rats. Melatonin also decreased ER stress markers (GRP78, ATF6, IRE1α, and PERK) and reduced pro-apoptosis markers (Bax, Bak, P-JNK, cleaved caspase 3 and 9) while increasing Bcl2 levels and melatonin receptor 2 (MT2) expression. These findings suggest that melatonin may protect against muscle atrophy in obese and diabetic conditions by mitigating ER stress and calcium imbalance, highlighting its therapeutic potential. Full article

Background: The prevalence of type 2 diabetes mellitus (T2DM) has been steadily increasing over the past few decades, largely due to the rise in obesity rates. Bariatric surgery is a gastrointestinal surgical treatment focused on achieving weight loss in individuals with obesity. A more recent and growing body of literature has shown that improvements in glycemic control and insulin sensitivity and even the remission of T2DM can be seen in patients with obesity and T2DM (“diabesity”), before significant weight loss is achieved, justifying the modification of the terminology from bariatric to metabolic and bariatric surgery (BMS). Main Results: This narrative review provides an overview of the latest literature on BMS for diabesity, discussing key publications and exploring controversial and diverging hypotheses. Robust scientific evidence supporting the use of BMS as a treatment for diabesity has been garnered and new venues are being explored, suggesting the novel and complementary role of the latest generation of incretin-based pharmacotherapy. Conclusions: BMS has emerged as a valuable treatment option for patients with diabesity, offering significant improvements in glycemic control, weight loss, and overall health. The limitations of the currently available and reviewed literature include the flawed knowledge of the mechanisms of action and long-term effects of BMS for the treatment of diabesity. Further studies are also warranted to refine the patient selection criteria and optimal surgical techniques and to evaluate the impact of surgery on T2DM outcomes in diverse populations. Lastly, there is a scarcity of studies investigating the efficacy of BMS against incretin-based pharmacotherapy. The non-systematic, narrative nature of this review and its implicit subjective examination and critique of the body of literature are to be considered additional and intrinsic limitations. Full article

Multiple modifications of metabolic syndrome diagnostic criteria have been made—NCEP: ATP III (from 2001, modified in 2004), IDF (2005), IDF Consortium (2009), or Polish Scientific Society Consortium standards (2022) are now frequently in use. Hepatosteatosis and hepatofibrosis are commonly mentioned aspects of metabolic syndrome that greatly increase the likelihood of developing complications. The objective of the study was to assess different diagnostic criteria for metabolic syndrome based on the prevalence of liver steatosis and fibrosis. A retrospective analysis was conducted on the medical data of 2102 patients. Out of all the single criteria, meeting the obesity criterion based on waist circumference showed the highest increase in the risk of hepatosteatosis (by 64–69%, depending on the definition used)—hypertriglyceridemia increased the risk of hepatofibrosis by 71%. Regardless of the specific criteria used, patients with metabolic syndrome had a 34–36% increased likelihood of developing hepatosteatosis—the probability of hepatofibrosis varied between 42% and 47% for the criteria established in 2004, 2005, and 2009, while the Polish 2022 criteria were not statistically significant (p = 0.818). It seems appropriate to establish consistent metabolic syndrome diagnostic criteria—the 2009 IDF guidelines are the most effective in assessing hepatosteatosis and fibrosis risk. Full article

Several hallmarks of metabolic syndrome, such as dysregulation in the glucose and lipid metabolism, endothelial dysfunction, insulin resistance, low-to-medium systemic inflammation, and intestinal microbiota dysbiosis, represent a pathological bridge between metabolic syndrome and diabesity, cardiovascular, and neurodegenerative disorders. This review aims to highlight some therapeutic strategies against metabolic syndrome involving integrative approaches to improve lifestyle and daily diet. The beneficial effects of foods containing antioxidant polyphenols, intestinal microbiota control, and physical activity were also considered. We comprehensively examined a large body of published articles involving basic, animal, and human studie, as well as recent guidelines. As a result, dietary polyphenols from natural plant-based antioxidants and adherence to the Mediterranean diet, along with physical exercise, are promising complementary therapies to delay or prevent the onset of metabolic syndrome and counteract diabesity and cardiovascular diseases, as well as to protect against neurodegenerative disorders and cognitive decline. Modulation of the intestinal microbiota reduces the risks associated with MS, improves diabetes and cardiovascular diseases (CVD), and exerts neuroprotective action. Despite several studies, the estimation of dietary polyphenol intake is inconclusive and requires further evidence. Lifestyle interventions involving physical activity and reduced calorie intake can improve metabolic outcomes. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as the most prevalent chronic liver disease, closely linked to the escalating rates of diabesity. The Western diet’s abundance of fat and fructose significantly contributes to MASLD, disrupting hepatic glucose metabolism. We previously demonstrated that a high-fat and high-fructose diet (HFHFD) led to increased body and liver weight compared to the low-fat diet (LFD) group, accompanied by glucose intolerance and liver abnormalities, indicating an intermediate state between fatty liver and liver fibrosis in the HFHFD group. Sirtuins are crucial epigenetic regulators associated with energy homeostasis and play a pivotal role in these hepatic dysregulations. Our investigation revealed that HFHFD significantly decreased Sirt1 and Sirt7 gene and protein expression levels, while other sirtuins remained unchanged. Additionally, glucose 6-phosphatase (G6Pase) gene expression was reduced in the HFHFD group, suggesting a potential pathway contributing to fibrosis progression. Chromatin immunoprecipitation analysis demonstrated a significant increase in histone H3 lysine 18 acetylation within the G6Pase promoter in HFHFD livers, potentially inhibiting G6Pase transcription. In summary, HFHFD may inhibit liver gluconeogenesis, potentially promoting liver fibrosis by regulating Sirt7 expression. This study offers an epigenetic perspective on the detrimental impact of fructose on MASLD progression. Full article