Search Results (1,501)

Type 2 diabetes mellitus (T2DM) and obesity represent a growing global public health challenge, strongly associated with excess body weight, unhealthy dietary habits, and a sedentary lifestyle. The ketogenic diet (KD), characterized by very low carbohydrate intake, moderate protein intake, and high fat consumption, induces a metabolic state known as ketosis, in which the body switches from glucose to fat as its primary energy source. KD has gained increasing interest as a strategy to improve glycemic control, reduce body weight, and improve lipid profiles in individuals with obesity and T2DM. The purpose of this narrative review is to summarize the current scientific evidence on the effects of KD on key metabolic parameters, including blood glucose levels, glycated hemoglobin (HbA1c), body weight, and body composition. The analysis is based on peer-reviewed articles retrieved from PubMed, Embase, and Scopus with particular emphasis on clinical studies that provide robust evidence on the efficacy and safety of KD in the treatment of metabolic disorders. Full article

Background/Objectives: The Prognostic Nutritional Index (PNI), which integrates serum albumin and lymphocyte count, reflects both nutritional and inflammatory status. However, its role in early renal function decline among patients with type 2 diabetes (T2D), particularly in relation to glycemic control, remains unclear. This study aimed to: (1) characterize the dose–response relationship between PNI and early renal function decline in type 2 diabetes using restricted cubic splines; (2) identify whether glycemic control (HbA1c) modifies the PNI–renal decline association; and (3) evaluate the clinical utility of combining PNI and HbA1c for risk stratification. Methods: We analyzed data from 1711 community-based participants with T2D who had preserved renal function at baseline. The PNI was calculated as serum albumin (g/L) + 5 × lymphocyte count (×10⁹/L). The primary outcome was a composite of rapid estimated glomerular filtration rate (eGFR) decline (>3 mL/min/1.73 m² per year) or incident chronic kidney disease (CKD) stage 3. Restricted cubic spline models, multivariable regression, and Johnson–Neyman analyses were used to examine non-linearity and effect modification by glycated hemoglobin (HbA1c). Results: A consistent inverse linear association was observed between PNI and the rate of eGFR decline (P for non-linearity > 0.05). Johnson–Neyman analysis further demonstrated that the protective association of PNI was statistically significant within an HbA1c range of 7.24% to 8.71%. Stratification by clinical cut-offs revealed a significant effect modification by glycemic status. The inverse linear association between PNI and renal risk was most pronounced under hyperglycemic stress, as evidenced by the markedly elevated incidence (50.0%) among individuals with both poor glycemic control (HbA1c ≥ 8%) and low PNI (<50). Conversely, under good glycemic control (HbA1c < 8%), this inverse association was substantially attenuated, with a lower incidence observed in the low-PNI subgroup (6.7%) than in the high-PNI subgroup (15.9%). These findings indicate that the protective role of PNI is conditional upon the glycemic milieu. Conclusions: The PNI demonstrates a stable linear association with early renal function decline in T2D, with its protective effect most pronounced at suboptimal HbA1c levels. Combining PNI and HbA1c effectively identifies a high-risk subgroup characterized by synergistic risk, underscoring the need for integrated nutritional and glycemic management. Full article

Background: Diabetic retinopathy is a leading cause of vision impairment and a significant complication of diabetes mellitus, especially in low- and middle-income countries. This study aimed to identify the barriers affecting diabetic retinopathy screening among people with diabetes mellitus. Methods: This cross-sectional study was conducted between April and October 2024 at the National Center for Diabetes, Endocrinology and Genetics. Data collection was performed using a structured, validated electronic questionnaire adapted from previous studies. Sample size calculation was carried out before data collection. Data were collected using a structured electronic questionnaire. A total of 998 responses were included in the study. The collected data incorporated sociodemographic characteristics, diabetes history, screening practices, and reported barriers. Descriptive and categorical data analyses were performed. Results: Of 998 participants, 82% were over 50 years old, 79% had type 2 diabetes mellitus, and 30% had never had an eye examination. Diabetic retinopathy was diagnosed in 12%. The main barriers to regular attendance among those previously screened (699) were as follows: lack of awareness of its importance (11%), believing that being asymptomatic made screening unnecessary (19%), and transportation difficulties (14%). Among those never screened (299), 56% lacked awareness, 62% believed being asymptomatic negates the need for screening, and 13% faced transportation difficulties. Age > 50 years, higher educational level, availability of health insurance, longer duration of diagnosis of diabetes mellitus, and HbA_1c > 7% were significantly associated with prior screening (p < 0.05). Conclusions: Public health strategies should enhance the education provided to people and physician–person communication and remove logistical obstacles to improve screening compliance. Full article

Metabolic syndrome (MetS) is characterised by cardiometabolic risk factors and is closely associated with increased oxidative stress and chronic low-grade inflammation. MetS is largely driven by adverse lifestyle behaviours, particularly physical inactivity, and regular physical activity is recognised as a central strategy for its prevention and management. This study aimed to assess the long-term impact of a five-year follow-up period of physical activity on oxidative stress, inflammatory biomarkers, and cardiometabolic health in adults with MetS. Forty participants diagnosed with MetS (50% men, aged 55–75 years) were selected and stratified into two groups: those who increased their physical activity and those who reduced it during the intervention. Physical activity was assessed using metabolic equivalent task minutes per week (MET·min/week), and evaluations were performed at baseline, 3 years, and 5 years. Participants who increased physical activity showed a progressive reduction in reactive oxygen species (ROS) produced by peripheral blood mononuclear cells (PBMCs), together with a decrease in plasma malondialdehyde (MDA). Antioxidant enzyme activities, including catalase and superoxide dismutase, exhibited a favourable long-term profile, with recovery or maintenance of higher activity levels by the end of follow-up, reflecting enhanced endogenous antioxidant defence. Inflammatory status improved and was characterised by a reduction in myeloperoxidase (MPO) activity and a sustained increase in plasma interleukin-15 (IL-15). These participants also showed reductions in body weight, body mass index (BMI), waist circumference, fasting glucose, and glycosylated haemoglobin A1c (HbA1c), consistent with improved insulin sensitivity and metabolic control. Participants who reduced physical activity tended to show unfavourable trajectories in several biomarkers. Increasing physical activity over time is associated with substantial improvements in redox balance, inflammatory status, and cardiometabolic health in adults with MetS. These findings reinforce the central role of physical activity as a fundamental therapeutic component within lifestyle interventions aimed at mitigating metabolic dysfunction and preventing MetS progression. Full article

Background/Objective: The risk of bleeding is part of blood flow pathophysiology in diabetes mellitus (DM), and there may be potential for the relationship between blood cell indices and estimated whole blood viscosity (eWBV) in DM. However, red blood cell (RBC) indices, platelet ratios, and lymphocyte ratios have been part of routine haematology tests in clinical medicine including diabetes management. This study investigated two research questions. Firstly, how does eWBV correlate with RBC indices, platelet ratios, and lymphocyte ratios? Secondly, which parameters of RBC in routine full blood count (FBC) correlate more with glycated haemoglobin (HbA1c) changes? Methods: This was a laboratory-based clinical observational cohort study using secondary data from ongoing research. Data collected included FBC and biochemistry (HbA1c and serum protein level). Dependent variables were platelet and lymphocyte ratios as well as eWBV. Results: Averages for all parameters in the cross-sectional data were within normal range, except high HbA1c (7.67%) and marginally high monocyte-to-lymphocyte ratio. In the periodic cohort analysis, only RBC distribution width showed a significant difference (p < 0.04) between cohort groups, but least correlated with HbA1c changes. Further analysis for correlations among change scores showed that RBC had the strongest positive linearity for HbA1c (r = 0.30) and among the top three for eWBV (r = 0.54), while mean cell volume (MCV) has the strongest inverse for HbA1c (r = −0.47). Conclusions: The ongoing clinical use of RBC variables is superior to profiles of platelet and/or lymphocyte ratios in assessing the potential risk of bleeding (i.e., hypo-viscosity) in diabetes. Full article

Probiotics, whether consisting of a single strain or multiple strains, are attracting growing interest in the management of type 2 diabetes mellitus (T2DM). However, their efficacy remains a matter of controversy and requires careful consideration. Accordingly, this meta-analysis aimed to compare the efficacy of single-strain to that of multi-strain probiotics supplementation on glycated haemoglobin (HbA1c) and fasting blood glucose (FBG) levels in adults with T2DM. Nineteen articles published between 2017 and 2024 obtained from 4 databases (Cochrane, Web of Science, Scopus, and PubMed) were included. These interventions, conducted in a total of 1159 participants, lasted from 6 to 24 weeks and were based on clearly identified probiotic formulations, with assessments of HbA1c and FBG. The results showed that, overall, probiotic supplementation had no significant effect on HbA1c (−0.24%; 95% CI [−0.76; 0.27]; p = 0.36), although a trend towards reduction was observed for single-strain formulations (−0.57%; p = 0.05). Regarding FBG, only the multi-strain group showed a significant reduction (−0.76; 95% CI [−1.18; −0.34]; p < 0.001), while the effect of the single-strain formulation was not significant. The comparison between the two formulations (Wald test) showed that there was no significant difference (p ≤ 0.05). However, high heterogeneity (I² > 75%) and variable strains/doses limit confidence in these findings. Full article

Type 1 Diabetes (T1D) is thought to result from the interaction of genetic and environmental factors, with different studies highlighting a potential role for the gut microbiota and its metabolites in modulating immune responses and disease development. We hypothesized that patients with T1D exhibited altered levels of circulating bacterial metabolites compared with healthy controls (HC), and that these metabolite profiles were associated with key demographic, clinical, and analytical features of the disease. A total of 91 T1D patients and 58 HC were recruited. Plasma samples were collected and analyzed with gas chromatography coupled to mass spectrometry for the detection of the metabolites: short-chain fatty acids (SCFAs: acetate [AA], propionate [PA], isobutyrate [IBA], butyrate [BA], isovalerate [IVA], valerate [VA], and methyl valerate [MVA]), medium-chain fatty acids (MCFAs: hexanoate [HxA] and heptanoate [HpA]) and para-cresol (p-cresol). We also calculated the ratios between the different SCFAs with AA. T1D patients showed significantly higher circulating AA levels than HC, along with reduced PA/AA and IBA/AA ratios, indicating an altered SCFA profile. SCFA diversity was lower in T1D patients, with reduced detection of BA, and total SCFA levels were increased mainly due to elevated AA. AA levels were higher and SCFA ratios lower in women with T1D compared with healthy women, while p-cresol levels were higher in men with T1D than in healthy men. In T1D patients, AA levels positively correlated with HbA1c, whereas PA/AA, IBA/AA, and BA/AA ratios showed negative correlations, particularly in women. MV/AA and non-AA/AA ratios were inversely associated with glucose levels, again, mainly in women. p-cresol levels correlated positively with age and ferritin and were higher in T1D patients with liver dysfunction or hypertension. Therefore, we can conclude that T1D is associated with a marked alteration in circulating gut-derived metabolites, characterized by increased AA levels, particularly in women, and an imbalance in SCFA ratios that correlates with glycemic control. These findings, together with the associations observed for p-cresol and metabolic comorbidities, support a role for the gut microbiota–host metabolic axis in T1D. Full article

Background: Plasticisers with endocrine-disrupting potential are ubiquitous and associate with obesity and type-2 diabetes (T2D), with higher levels reported in the Middle East. However, no data exist on plasticiser exposure in Bahrain where T2D affects 15% of the national population. Methods: An observational exploratory study in T2D (n = 60) and controls (n = 96), analysed for 24 h urinary plasticiser levels (liquid chromatography tandem mass spectrometry (LC-MS/MS)). Correlation and generalised linear model (GLM) analyses were employed to examine associations. Results: T2D were older (p < 0.001), had higher body mass index (BMI) (p < 0.001), body weight (p < 0.001) and glycosylated haemoglobin A1c (HbA1c) (p < 0.001). Correlation analysis revealed differences in inter-plasticiser, and plasticiser and biomarker relationships, with loss or reversal in T2D compared to controls. Mono-n-butyl phthalate (MnBP) levels were higher in T2D (p = 0.04); however, regression analysis revealed significant association with age. The GLM analyses demonstrated marked differences in the levels of mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), monoethyl phthalate (MEP) and bisphenol S (BPS), with lower levels in T2D versus controls (B = −3.41, p = 0.01; B = −5.28, p < 0.001; B = −8.94, p < 0.001; B = −6.09, p = 0.006, respectively); however, these contrasts appeared to be substantially confounded by BMI and/or age. Positive influence of age and negative influence of BMI when observed across the full dataset were generally reversed in T2D. Levels were complementary to those previously reported for the Middle East. Conclusions: The study indicates the phthalate levels in Bahrain are elevated though complementary to studies of phthalates in the Middle East; within those levels, the study indicates differential exposure–response relationships with plasticisers, influenced by age and BMI, in those with T2D compared to healthy controls. Full article

Using colorimetric ELISA, this study aims to assess the impact of Gum Arabica (GA) consumption on functional molecular plasma biomarkers of chronic kidney disease (CKD) via a prospective cohort of GA-consumers (cases) vs. non-consumer (age- and CKD stage-matched) controls. Cohort’s hypertension (92.5%), dyslipidemia (64.8%), and diabetes mellitus (54.8%) were prevalent; the mean CKD duration was 6.94 years (SD 7.8) for both study groups. Comparable eGFR, sCr, ESR, CRP, HbA1c, FPG, UA, and fasting lipid parameters were in both study arms. In consumer cases, the mean duration of GA-consumption was 1.3 ± 1.1 (range 0.25–6) years with a mean dose of 1.7 ± 1.0 (range 0.5–6) spoons per day. Leucine-rich alpha 2-glycoprotein, plasminogen activator inhibitor 1, sirtuin 1, and SOST–sclerostin 1 were significantly (p value < 0.01) of lower concentrations, but lipocalin 2 and uromodulin were invariably (p value < 0.05) greater in the GA-consumer cases than those of controls. Strikingly, cystatin C, myeloperoxidase, orosomucoid 1, and symmetric dimethylarginine lacked any substantial variations in the GA-consumer cases vs. those in controls (p value > 0.05). Proportional correlations of CKD duration–PAI1 levels and sCr-lipocalin 2 levels but inverse correlations of orosomucoid 1-hypertension duration and SDMA-DBP were evident in cases. Full article

Background/Objectives: Insulin resistance (IR) is a relevant metabolic concern in patients with rheumatic diseases; however, data regarding its clinical influence on the systemic sclerosis (SSc) phenotype is lacking. This study aimed to evaluate the characteristics of patients exhibiting IR in a monocentric SSc cohort. Methods: We conducted a cross-sectional study on 178 SSc patients, stratified according to the presence of IR, defined as a HOMA-IR value >1.85 for men and >2.07 for women, based on thresholds previously validated in the Estudio Epidemiológico de la Insuficiencia Renal en España (EPIRCE) cross-sectional study. The rationale for applying the current cut-offs is based on its discriminative potential when using sex- and age-specific thresholds in a nondiabetic population. This approach is particularly applicable to SSc, where the prevalence of diabetes is very low and the median ages of the two cohorts are comparable. Data collected included demographic-, clinical-, laboratory-, pulmonary function-, capillaroscopic-, and treatment-related parameters. A multivariable logistic regression model was used to identify independent predictors of IR. Results: Patients with IR (n = 76) had a significantly higher prevalence of diffuse cutaneous subset (26.3% vs. 11.8%, p = 0.012) and interstitial lung disease (39.5% vs. 17.6%, p = 0.001), along with the positivity for anti-Scl70 antibodies and the current presence of musculoskeletal symptoms (p = 0.021) and digital ulcers (p = 0.037). As expected, body mass index (BMI) was significantly higher in the IR population (24.6 ± 5.2 vs. 22.9 ± 4.1, p = 0.012), along with fasting glucose, insulin, HOMA-IR, and HbA1c levels. IR patients exhibited higher percentages of dyslipidemia and liver steatosis. Medications such as hydroxychloroquine, statins, and Iloprost were more frequently used in the IR group; as for corticosteroids usage (21.1% vs. 5.9%, p = 0.002), however, cumulative glucocorticoid dosage did not differ between the groups. In multivariable analysis, BMI (OR 1.09; p = 0.038) and interstitial lung disease (ILD) (OR 3.03; p = 0.034) were independent predictors of IR. Conclusions: In SSc, IR is associated with ILD, digital ulcers, musculoskeletal involvement, and anti-Scl70 autoantibodies. Full article

Background/Objective: The rising prevalence of Type 2 Diabetes Mellitus (T2DM), coupled with sedentary behavior and an increase in obesity rates in South Asian countries, calls for effective management strategies. We aimed to assess the efficacy of lifestyle interventions on glycemic control among adults with T2DM in South Asian countries. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to assess the effectiveness of lifestyle interventions on glycemic control in adults diagnosed with T2DM in South Asia. We conducted a comprehensive search in CINAHL, Embase, PubMed, Cochrane Library, Web of Science (WoS), and Scopus to identify related studies published from 2000 to 13 June 2024. We assessed the risk of bias using the ROB 2.0 tool and calculated the pooled mean differences in HbA1c and FBG levels under a random-effects model. We conducted subgroup and leave-one-out sensitivity analyses to assess and explore sources of heterogeneity. PROSPERO Registration: CRD42024552286. Results: We included 16 RCTs with a total of 1499 participants. Lifestyle interventions reduced HbA1c levels by 0.86% (95% CI: −1.30 to −0.42, p < 0.01) and FBG levels by 22.49 mg/dL (95% CI: −32.88 to −12.10, p < 0.01). We observed substantial heterogeneity (I² = 98% for HbA1c and I² = 87% for FBG). Subgroup analyses indicated larger HbA1c reductions in long-term (−1.44%) than short-term trials (−0.62%), and greater FBG decreases in long-term (−23.7 mg/dL) versus short-term studies (−22.5 mg/dL). Physical activity interventions had the largest improvements (HbA1c −0.99%; FBG −26.1 mg/dL), followed by dietary (HbA1c −0.59%; FBG −15.8 mg/dL) and combined programs (HbA1c −0.55%). Participants aged >50 years achieved greater glycemic improvements (HbA1c −0.92%; FBG −24.0 mg/dL) compared to younger adults (HbA1c −0.60%; FBG −21.3 mg/dL). Despite high heterogeneity, sensitivity analyses confirmed the robustness of the overall findings. Conclusions: Lifestyle modifications yielded a clinically significant reduction in HbA1c and FBG in adults with T2DM in South Asia. Although heterogeneity of the included studies was substantial, the direction of the effects was uniformly consistent across subgroups. To further validate these findings and assess their long-term effects, large-scale and standardized RCTs conducted for longer durations are necessary. Full article

Background/Objectives: Specific pharmacological osteoporosis therapy (SPOT) is regarded as a key intervention to reduce fracture risk and improve musculoskeletal function. Real-life data, particularly regarding functional muscular outcomes and pain trajectories, remain limited. This study aimed to longitudinally analyze bone mineral density, laboratory parameters, handgrip strength, functional performance, and pain symptoms under guideline-based SPOT. Methods: In this monocentric prospective real-life observational study, 178 patients (80.9% women; median age 82 years) with confirmed osteoporosis were followed for a median of four years. All patients received guideline-recommended antiresorptive or osteoanabolic therapy. Analyses included T-scores, 25(OH)D, calcium, handgrip strength, Chair Rise Test (CRT), tandem stance (TS), pain parameters, alkaline phosphatase (AP), HbA1c, fractures, comorbidities, and body mass index (BMI). Time-dependent changes were evaluated using linear mixed-effects models. Results: Bone mineral density improved highly significantly (ΔT-score ≈ +0.45 SD; p < 0.001), with no differences between therapy groups (antiresorptive vs. osteoanabolic) or BMI categories. Serum 25(OH)D levels increased markedly (Δ ≈ +20 nmol/L; p < 0.001), while calcium levels showed a small but highly significant decrease (Δ ≈ −0.047 mmol/L; p < 0.001), particularly under antiresorptive treatment. Dominant (Δ ≈ −1.95 kg; p < 0.001) and non-dominant handgrip strength (Δ ≈ −0.83 kg; p = 0.046) decreased significantly. In contrast, functional performance improved significantly: CRT time decreased by ~1 s (p = 0.004), and TS time increased by ~1 s (p = 0.007). Back pain decreased highly significantly (Δ ≈ −1.5 NRS; p < 0.001), while pain-free walking time (Δ ≈ +38 min; p = 0.031) and pain-free standing time (Δ ≈ +31 min; p = 0.038) both increased significantly. AP levels decreased significantly (p = 0.003), particularly among normal-weight patients. HbA1c changes were not significant. Overall, 73% of patients had at least one major osteoporotic fracture. Conclusions: In this real-life cohort, guideline-based specific pharmacological osteoporosis therapy was associated with significant improvements in bone mineral density, vitamin D status, functional performance, and pain-related outcomes. Despite a moderate decline in handgrip strength, balance- and mobility-related functional parameters improved, suggesting preserved or even enhanced functional capacity in daily life. These findings provide real-world evidence on the associations between SPOT, laboratory parameters, functional performance, and pain outcomes in a very elderly and multimorbid population. Full article

Background/Objectives: Type 2 diabetes (T2D) is a chronic metabolic disorder closely linked to cardiovascular disease and obesity and notably influenced by lifestyle and dietary patterns. The Mediterranean diet has well-established benefits across multiple cardiometabolic risk factors, including those relevant to diabetes. This study aimed to investigate the degree to which adults with T2D adhere to a Mediterranean dietary pattern and to examine how such adherence relates to glycemic and lipidemic regulation. Methods: This cross-sectional study included 100 adults with T2D (54 men and 46 women). Adherence to the Mediterranean diet was assessed using the Mediterranean Diet Score (MDS). Demographic, anthropometric, lifestyle, and clinical data were collected, and glycemic and lipid parameters were analyzed. Associations between Mediterranean diet adherence and metabolic outcomes were examined using correlation analyses and multivariable regression models adjusted for relevant confounders. Results: Most participants showed low adherence to the Mediterranean diet. A significant inverse association was observed between Mediterranean diet adherence and hemoglobin A1c (HbA1c) levels, with individuals scoring ≤35 on the MDS demonstrating higher HbA1c levels. Similar trends were observed in the lowest tertile of adherence. Notably, each one-point increase in MDS predicted a 0.13% reduction in HbA1c. In multivariable regression analyses, Mediterranean diet adherence remained the strongest predictor of glycemic control, independent of age, body mass index (BMI), sex, smoking status, physical activity and the number of antidiabetic treatments. Higher adherence was also significantly associated with lower low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels, as well as higher high-density lipoprotein cholesterol (HDL) concentrations. Conclusions: Greater adherence to the Mediterranean diet is independently associated with improved glycemic regulation and a more favorable lipid profile in adults with T2D. These findings support the Mediterranean diet as a valuable non-pharmacologic strategy for optimizing metabolic outcomes in people with T2D. Full article

Prediabetes is a serious and major global problem afflicting approximately 21% of the world’s population. It is the intermediate stage between normal glucose levels and type 2 diabetes mellitus (T2DM). Prediabetes is associated with major complications including the development of T2DM and increased cardiovascular disease (CVD). It can be easily diagnosed with an inexpensive plasma glucose level and/or a hemoglobin A1c (HbA1c) measurement. The mainstay of treatment is intensive lifestyle (ILS) intervention, including reduction in calories, especially saturated fats, refined carbohydrates, etc., coupled with regular physical activity of 150 min per week since ILS changes, with at least a 5% weight loss, have been shown to reduce progression to T2DM in multiple studies globally. Also, metformin therapy has been shown to prevent the progression to T2DM. In conclusion, serious consideration by guideline committees to classify prediabetes as a disease is highly recommended based on its global burden, easy and cost-effective diagnosis, association with serious conditions of diabetes and CVD, and effective ILS intervention. Therapy targeting those at an especially high risk for T2DM, such as persons with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) with values ≥ 110 mg/dL (6.1 mmol/L), and/or HbA1c ≥ 6.0% (42 mmol/mol) coupled with overweightness or obesity. Full article

Background: Irisin, a muscle-derived hormone, enhances the energy metabolism by activating the brown adipose tissue and acts as a bone-forming agent across the entire life span. No consistent clinical data in humans have been published so far to highlight if blood irisin as glucose/bone biomarker should be refined based on the vitamin D status (deficient or sufficient). Therefore, we aimed to objectively assess the level of irisin in female adults with abnormal and normal vitamin D status, as reflected by the level of 25-hydroxyvitamin (25OHD) in relationship with glucose and bone metabolic parameters. Methods: This pilot, prospective, exploratory study included eighty-nine menopausal women aged over 50. We excluded subjects with malignancies, bone and metabolic disorders, insulin treatment, and active endocrine disorders. Fasting profile included glycaemia, insulin, and glycated haemoglobin A1c (HbA1c). Then, 75 g oral glucose tolerance test (OGTT) included glycaemia and insulin assay after 60 and 120 min. Bone status involved bone turnover markers and central dual-energy X-ray absorptiometry providing bone mineral density (BMD) and trabecular bone score. Results: Eighty-nine subjects were included in the following two groups depending on 25OHD: vitamin D-deficient (VDD) group (N = 48; 25OHD < 30 ng/mL) and vitamin D-sufficient (VDS) group (N = 41; 25OHD ≥ 30 ng/mL). The two groups had similar age and menopausal period (62.29 ± 10.19 vs. 63.56 ± 8.16 years, respectively; 15.82 ± 9.55 vs. 16.11 ± 9.00 years, p > 0.5 for each). A statistically significant higher body mass index (BMI) was found in VDD vs. VDS group (32.25 ± 5.9 vs. 28.93 ± 4.97 kg/m², p = 0.006). Circulating irisin was similar between the groups as follows: median (IQR) of 91.85 (44.76–121.76) vs. 71.17 (38.76–97.43) ng/mL, p = 0.506. Fasting profile and OGTT assays showed no between-group difference. Median HOMA-IR in VDD group pointed out insulin resistance of 2.67 (1.31–3.29). Lowest mean/median T-scores at DXA for both groups were consistent with osteopenia category, but they were confirmed at different central sites as follows: femoral neck in both groups [VDD versus VDS group: −1.1 (−1.20–−0.90) vs. −1.1 (−1.49–−0.91), p = 0.526, respectively], only at lumbar spine for VDS group (T-score of −1.18 ± 1.13). The correlations between irisin and the mentioned parameters displayed a different profile when the analysis was performed in the groups with different 25OHD levels. In VDD group, irisin levels statistically significantly correlated with serum phosphorus (r = −0.32, p = 0.022), osteocalcin (r = −0.293, p = 0.038), P1NP (r = −0.297, p = 0.04), HbA1c (r = 0.342, p = 0.014), and BMI (r = 0.408, p = 0.003). Conclusions: This pilot study brings awareness in the analysis of irisin in relationship with glucose and bone-related biomarkers correlates, showing a distinct type of association depending on 25OHD level, which might represent an important crossroad in the multitude of irisin-activated signal transduction pathways. Full article