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The incidence and prevalence of metabolic and musculoskeletal diseases are increasing. Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, inflammation, advanced glycation end-product accumulation and increased oxidative stress. These characteristics can negatively affect various aspects of muscle health, including muscle mass, strength, quality and function through impairments in protein metabolism, vascular and mitochondrial dysfunction, and cell death. Sarcopenia is a term used to describe the age-related loss in skeletal muscle mass and function and has been implicated as both a cause and consequence of T2DM. Sarcopenia may contribute to the development and progression of T2DM through altered glucose disposal due to low muscle mass, and also increased localized inflammation, which can arise through inter- and intramuscular adipose tissue accumulation. Lifestyle modifications are important for improving and maintaining mobility and metabolic health in individuals with T2DM and sarcopenia. However, evidence for the most effective and feasible exercise and dietary interventions in this population is lacking. In this review, we discuss the current literature highlighting the bidirectional relationship between T2DM and sarcopenia, highlight current research gaps and treatments, and provide recommendations for future research.

Cardiovascular disease (CVD) is the most common complication of diabetes mellitus (DM). To prevent morbidity and mortality among patients with type 2 diabetes mellitus (T2DM), optimization of glycemic status and minimizing CVD risk factors is essential. As Nepal has limited data on these CVD risk parameters, we assessed the prevalence of poor glycemic control, CVD risk factors, and their clustering among patients with T2DM. Using a cross-sectional study design, we collected data of 366 patients with T2DM. We applied a multistage cluster sampling technique and used the WHO STEPS tools. Binary logistic and Poisson regression was applied to calculate odds and prevalence ratio of clustering of risk factors, considering P< 0.05 statistically significant. The mean age of participants was 54.5±10.7 years and 208 (57%) were male. The prevalence of poor glycemic control was 66.4% (95% C.I: 61.5-71.2). The prevalence of smoking, alcohol users, inadequate fruit and vegetables intake and physical inactivity were 18% (95% C.I:14 to 21.9), 14.8% (95% C.I:11.1 to 18.4), 98.1% (95% C.I: 96.7-99.4), and 9.8% (95% C.I:6.7-12.8), respectively. Overall, 47.3% (95% C.I: 42.1-52.4) were overweight and obese, 59% (95% C.I: 52.9-63) were hypertensive, and 68% (95% C.I: 63.2-72.7) had dyslipidemia. Clustering of two, three, four, five and more than five risk factors was 12.6%, 30%, 30%,19%, and 8.7%, respectively. Four or more risk factors clustering was significantly associated with gender, age, level of education, T2DM duration, and use of medication. Risk factors clustering was significantly higher among males and users of anti-diabetic medications with prevalence ratio of 1.14 (95% C.I:1.05-1.23) and 1.09 (95% C.I: 1.09-1.18)], respectively. The majority of the patients with T2DM had poor glycemic control and CVD risk factors. Policies and programs focused on the prevention and better management of T2DM and CVD risk factors should be implemented to reduce mortality in Nepal.

Hypertension is a major global public health problem. Elevated blood pressure can cause cardiovascular and kidney diseases. We assessed the effectiveness of health education sessions and home support programs in reducing blood pressure among patients with uncontrolled hypertension in a suburban community of Nepal. We conducted a community-based, open-level, parallel-group, cluster randomized controlled trial in Birendranagar municipality of Surkhet, Nepal. We randomly assigned four clusters (wards) into intervention and control arms. We provided four health education sessions, frequent home and usual care for intervention groups over six months. The participants of the control arm received only usual care from health facilities. The primary outcome of this study was the proportion of controlled systolic blood pressure (SBP). The analysis included all participants who completed follow-up at six months. 125 participants were assigned to either the intervention (n = 63) or the control (n = 62) group. Of them, 60 participants in each group completed six months follow-up. The proportion of controlled SBP was significantly higher among the intervention participants compared to the control (58.3% vs. 40%). Odds ratio of this was 2.1 with 95% CI: 1.01-4.35 (p = 0.046) and that of controlled diastolic blood pressure (DBP) was 1.31 (0.63-2.72) (p = 0.600). The mean change (follow-up minus baseline) in SBP was significantly higher in the intervention than in the usual care (-18.7 mmHg vs. -11.2 mmHg, p = 0.041). Such mean change of DBP was also higher in the intervention (-10.95 mmHg vs. -5.53 mmHg, p = 0.065). The knowledge score on hypertension improved by 2.38 (SD 2.4) in the intervention arm, which was significantly different from that of the control group, 0.13 (1.8) (p<0.001). Multiple health education sessions complemented by frequent household visits by health volunteers can effectively improve knowledge on hypertension and reduce blood pressure among uncontrolled hypertensive patients at the community level in Nepal. ClinicalTrial.gov: NCT02981251.

Glomerular hyperfiltration has been associated with obesity, insulin resistance, and systolic blood pressure (SBP). However, previous studies are limited by confounders such as pre-existing diabetes or hypertension, or have used indirect measures of adiposity and insulin sensitivity (IS). Therefore, we examined the relationship between estimated glomerular filtration rate (eGFR) and IS measured by the hyperinsulinaemic euglycaemic clamp in a healthy population on no medications. We performed oral glucose tolerance test (OGTT) and measured % body fat (DEXA), BMI, blood pressure and M-value (hyperinsulinaemic euglycaemic clamp) in 104 individuals (44 females and 60 males). The majority of the study population (n = 89, 85.6%) were classified on their BMI as overweight/obese. eGFR was related to age, BMI, M-value (IS), 2-hour glucose levels post OGTT and white blood cell count (WBC) (all p < 0.05); but not to SBP (p = 0.1) or fasting glucose levels (p = 0.2). After adjustment for gender, BMI, SBP and WBC, the inverse association between eGFR and M-value (p = 0.001), and 2-hour glucose post OGTT (p = 0.02) persisted. In conclusion, although eGFR has been associated with BMI and blood pressure in previous studies, in our healthy population, eGFR was more closely related to markers of glucose metabolism (IS and 2-hour glucose post OGTT) than to BMI and blood pressure.

ObjectivesThis study explores the challenges experienced by Australian healthcare professionals (HCPs) in delivering type 2 diabetes care to people of culturally and linguistically diverse (CALD) backgrounds. We examined how sociocultural, linguistic and health systems factors influence their clinical practice.DesignA qualitative study employing semi-structured interviews was conducted from April to October 2024. Data were analysed using Braun and Clarke’s reflexive thematic analysis to identify patterns and themes in HCPs’ experiences, guided by a constructivist perspective.SettingsThe study was conducted in metropolitan Melbourne, Australia, across primary and tertiary healthcare settings.ParticipantsA purposive sample of 11 Australian HCPs from diverse disciplines, including general practice, pharmacy, nursing, endocrinology, dietetics and podiatry, participated. All had provided type 2 diabetes care to people of CALD backgrounds within the previous 12 months. Participants included both male and female professionals, many from ethnically diverse backgrounds.ResultsThree overarching themes were identified, reflecting HCPs’ perceived challenges to providing culturally responsive type 2 diabetes care to people of CALD backgrounds. These themes illustrated the multilevel challenges encountered by HCPs at the patient, organisational and provider levels, namely: (1) healthcare provision across diverse health literacy and cultural contexts, (2) navigating system gaps in multicultural clinical practice and (3) workforce preparedness gaps in culturally responsive care.ConclusionsHCPs remain committed to providing culturally responsive type 2 diabetes care but continue to face constraints, including limited cross-cultural training and exposure, inadequate interpreter access, time pressures and insufficient culturally adapted resources. Effective care in multicultural settings requires recognising patients’ culturally shaped beliefs about health and illness and embedding cultural humility, reflexivity and competence within professional practice, essential steps towards advancing equitable type 2 diabetes care across Australia’s diverse communities.

Background: Trends in global ageing underscore the rising burden of age-related cognitive decline and concomitant cardiometabolic diseases, including type 2 diabetes mellitus (T2DM). Carnosine, a naturally occurring dipeptide with anti-inflammatory, antioxidant and anti-glycating properties, has shown promise in animal models and limited human studies for improving cognitive function, insulin resistance and T2DM, but its therapeutic effects on cognition remain unclear. The aim of this study is to assess the effects of carnosine on cognitive function in individuals with prediabetes or well-controlled T2DM. Methods: This is a secondary analysis of a double-blind randomised controlled trial (RCT), whereby 49 adults with prediabetes or early-stage well-controlled T2DM were randomised to receive 2 g of carnosine or identical placebo daily for 14 weeks. At baseline and follow-up, cognitive function was assessed as a secondary outcome using the Digit-Symbol Substitution Test, Stroop test, Trail Making Tests A & B, and the Cambridge Automated Neuropsychological Test Battery (CANTAB). Results: In total, 42 adults (23 males and 19 females) completed the trial. There were no differences in participant anthropometry or cognitive functioning between carnosine and placebo groups at baseline (all p > 0.1). After the 14-week supplementation period, there were no differences between carnosine and placebo groups in change and follow-up values for any cognitive measures including Stroop, Digit Symbol Substitution Sest, Trail Making A/B or CANTAB (all p > 0.05). Adjustments for baseline cognitive scores, diabetic status, level of education, age or interaction effects with participants’ sex did not change the results. Conclusions: Carnosine supplementation did not improve cognitive measures in individuals with prediabetes or T2DM in this study. While larger trials may provide further insights, alternative factors—such as the relatively young and healthy profile of our cohort—may have contributed to the lack of observed effect. Future research should examine individuals with existing cognitive impairment or those at higher risk of cognitive decline to better define the therapeutic potential of carnosine in this context.

Background Weight loss achieved via energy restriction leads to significant losses in muscle and bone mass, potentially increasing risk for sarcopenia and osteoporosis. High‐intensity resistance and impact training (HiRIT) might attenuate weight loss–induced musculoskeletal declines. Our objective was to compare changes in physical function and body composition in older adults with obesity undertaking dietary weight loss combined with HiRIT or aerobic training (AT). Methods Sixty older adults (aged ≥ 60 years) with obesity (dual‐energy x‐ray absorptiometry determined body fat percentage ≥ 30% in men and ≥ 40% in women) and a mobility limitation (Short Physical Performance Battery [SPPB] score ≤ 11) were randomly assigned to either 12 weeks of supervised, centre‐based HiRIT or self‐directed, home‐based AT while consuming a hypocaloric diet (750–1000 kcal/day reduction in energy intake). Changes in physical function (primary outcome: gait speed) and body composition were compared between groups. Results A total of 49/60 randomised participants (mean age: 69.6 ± 6 years; 58% women; mean BMI: 32.9 ± 4.1 kg/m2) completed the trial. Gait speed increased following HiRIT compared with AT (mean difference: 0.07 m/s [95% CI: 0.01, 0.13]). Chair stand times decreased in both groups (HiRIT: −1.3 s [95% CI: −2.1, −0.4] vs. AT: −0.8 s [95% CI: −1.6, −0.04]) and HiRIT, but not AT, increased handgrip strength (HiRIT: 2.2 kg [95% CI: 0.6, 3.9] vs. AT: 0.7 kg [95% CI: −0.9, 2.3]) and SPPB scores (HiRIT: 0.9 [95% CI: 0.4, 1.3] vs. AT: 0.4 [95% CI: −0.04, 0.8]). Similar decreases in total body mass (HiRIT: −5.1 kg [95% CI: −6.7, −3.4] vs. AT: −4.9 kg [95% CI: −6.5, −3.3]), fat mass (HiRIT: −3.6 kg [95% CI: −5.0, −2.2] vs. AT: −3.3 kg [95% CI: −4.7, −2.0]), visceral fat (HiRIT: −32.1 cm2 [95% CI: −47.4, −16.8] vs. AT: −31.4 cm2 [95% CI: −46.1, −16.8]) and appendicular lean mass (HiRIT: −0.8 kg [95% CI: −1.4, −0.2] vs. AT: −1.2 kg [95% CI: −1.8, −0.6]) were observed. HiRIT was well tolerated with only seven minor adverse events compared with five reported in those who completed AT. Conclusion HiRIT appears to be safe and more effective than AT for improving gait speed in older adults with obesity undertaking dietary weight loss. Additional trials with larger sample sizes and longer durations are warranted to explore whether HiRIT can attenuate weight loss–related muscle and bone mass declines. Trial Registration: Australian New Zealand Clinical Trials: ACTRN12618001146280.

Obesity is highly prevalent in Western populations and is considered a risk factor for the development of renal impairment. Interventions that reduce the tissue burden of advanced glycation end-products (AGEs) have shown promise in stemming the progression of chronic disease. Here we tested if treatments that lower tissue AGE burden in patients and mice would improve obesity-related renal dysfunction. Overweight and obese individuals (body mass index (BMI) 26–39kg/m2) were recruited to a randomized, crossover clinical trial involving 2 weeks each on a low- and a high-AGE-containing diet. Renal function and an inflammatory profile (monocyte chemoattractant protein-1 (MCP-1) and macrophage migration inhibitory factor (MIF)) were improved following the low-AGE diet. Mechanisms of advanced glycation-related renal damage were investigated in a mouse model of obesity using the AGE-lowering pharmaceutical, alagebrium, and mice in which the receptor for AGE (RAGE) was deleted. Obesity, resulting from a diet high in both fat and AGE, caused renal impairment; however, treatment of the RAGE knockout mice with alagebrium improved urinary albumin excretion, creatinine clearance, the inflammatory profile, and renal oxidative stress. Alagebrium treatment, however, resulted in decreased weight gain and improved glycemic control compared with wild-type mice on a high-fat Western diet. Thus, targeted reduction of the advanced glycation pathway improved renal function in obesity.

Carnosine (CAR), an endogenous histidine-containing dipeptide, exhibits antioxidant and anti-inflammatory activity in various experimental models; however, its molecular mechanism of action remains poorly understood. Here, we demonstrate that the Michael adduct between CAR and 4-hydroxy-2-nonenal (HNE), which has been detected in previous studies in both in vitro and in vivo settings, mediates its bioactivity, particularly its antioxidant and anti-inflammatory responses, through Nrf2 activation. The CAR–HNE adduct was synthesized and its physicochemical, metabolic, and biological properties were evaluated. CAR–HNE exhibited high stability in biological matrices and retained the ability to transfer HNE to thiol nucleophiles at a slow rate under physiologically relevant conditions, consistent with electrophile-mediated Nrf2 activation. This kinetic behavior limits the cytotoxicity typically associated with free HNE while preserving the redox signaling capacity. CAR–HNE induced dose-dependent Nrf2 activation and NF-κB inhibition in cell-based assays without the hormetic toxicity observed for free HNE. Mechanistically, CAR–HNE may act as a redox-tunable electrophilic reservoir, restoring nucleophilic tone and modulating redox-sensitive transcription factors. In vivo, CAR–HNE attenuated DSS-induced colitis more effectively than equimolar doses of either carnosine or HNE alone. Proteomic analyses revealed modulation of canonical Nrf2-dependent antioxidant pathways. Our findings suggest a conceptual shift in carnosine biology: rather than acting as a classical antioxidant or carbonyl quencher, carnosine functions as a precursor of redox-active electrophilic adducts that transduce anti-inflammatory and antioxidant responses via controlled RCS signaling.

Complementary medicines (CMs) are widely used worldwide, with usage rates ranging from 24% to 71.3%. Despite their popularity, many CMs lack robust scientific support and can potentially lead to adverse health effects. Limited research exists on CMs-related adverse events and the role of CMs’ labels in conveying crucial information to consumers. This cross-sectional study investigated the usage, consumer perspectives, and influence of labels specifically on product-based CMs, including nutritional supplements, vitamins, minerals, probiotics, prebiotics, and herbal medicines. Practitioner-led therapies and mind-body practices were outside the scope of this research. Data were collected through an online questionnaire and analyzed using descriptive statistics and correlation analysis. The study enrolled 125 participants who were current CMs users. Pharmacies and supermarkets were the primary sources for CMs procurement. Participants’ perceptions of CMs effectiveness and safety were positively correlated. Label warnings prompted participants to seek additional information, but consultation with healthcare professionals was infrequent. Adverse reactions were reported by 18.5% of participants, with self-management approaches being common. Label warnings play a significant role in prompting consumers to seek more information about CMs. However, the limited engagement of healthcare professionals, especially pharmacists, suggests an opportunity for improved consumer education and pharmacist involvement in CMs-related discussions. Addressing these aspects can lead to safer CMs practices and informed decision-making among consumers.