Chronic metabolic diseases (CMDs) such as obesity, type 2 Diabetes mellitus (T2DM), metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular diseases (CVDs) represent an escalating global health crisis. The etiology and pathophysiology of CMDs are linked to persistent metabolic, inflammatory, and gut microbiome dysfunctions. Recombinant Live Biotherapeutic Products (rLBPs) are engineered microbes designed to deliver targeted metabolic, anti-inflammatory, or hormonal effects in situ, offering a promising alternative to conventional therapies. The development of the rLBPs is expected to bring a paradigm shift in the clinical management of chronic diseases. This chapter provides an overview of rLBPs by highlighting seminal examples of rLBPs, which are in the early phase of development for CMDs. It also deliberates on existing scientific, technical and regulatory challenges along with potential opportunities associated with the development of rLBPs.

Diabetic ulcers remain a significant clinical concern because of their poor healing, persistent inflammation, and increased infection risk. Chitosan and its derivatives have emerged as promising biomaterials for ulcer management due to their biocompatibility, biodegradability, mucoadhesiveness, pH responsiveness, and intrinsic properties, including hemostatic effects, antibacterial activity, anti-inflammatory properties, antioxidant capabilities, and self-healing capabilities. This review provides a comprehensive and current overview of chitosan-based approaches for diabetic ulcer management, focusing on both conventional and advanced biomaterials, including nanoparticles, hydrogels, nanofibers, microneedles, sponges, and 3D scaffolds. Special attention is given to stimuli-responsive chitosan systems designed to adjust drug release in response to specific cues, such as pH, reactive oxygen species, temperature, enzymes, or glucose levels. To underscore the translation potential, the review compiles commercialized products, recent patents, and clinical trials related to the management of diabetic ulcers based on chitosan formulations. Finally, the integration of AI-driven design with smart chitosan systems is proposed as a future direction towards personalized and predictive diabetic ulcer management.

A retrospective observational cohort study evaluating real-world outcomes in adults with type 1 diabetes and gastroparesis using automated hybrid closed loop insulin delivery systems (HCL).

All adults with type 1 diabetes and gastroparesis attending King's College Hospital diabetes service and using continuous glucose monitoring (CGM) from 5 October 2023 to 16 January 2025 were included. Glycaemic data (HbA_1c, CGM metrics), hypoglycaemia awareness (Gold score), diabetes distress (DDS2), and acute complications (DKA, severe hypoglycaemia) were collected from electronic health records and glucose platforms for 12 months pre- and post-HCL initiation.

From 1827 clinic attendees, 36 adults with gastroparesis were identified, with 17 initiating HCL. HCL and non-HCL groups had comparable baseline characteristics and metrics (HCL: Mean(SD) HbA_1c 70(21)mmol/mol [8.6(1.9)%]; Time in range (TIR) 36.8 (21.9) % vs. non-HCL: HbA_1c 71 (25) mmol/mol [8.6(2.3)%]; TIR 37.1(19.2)%, p = 0.73). Post-HCL, HbA_1c median(IQR) fell to 57(52.5-65.0) mmol/mol [7.4(7.0-8.1)%] (p < 0.001). TIR increased to 55.7(19.9)% (p < 0.001), with a significant reduction in Time above range Level 2 (TAR2) [>13.9 mmol/L/>250 mg/dL](32.7% to 14.5%, p = 0.014). Gold score improved (2.5 to 1.5, p = 0.019), but DDS2 remained unchanged. No increase in DKA or severe hypoglycaemia occurred.

Within a specialist multidisciplinary team setting, HCL systems significantly reduce HbA_1c without increasing risk of severe hypoglycaemia or DKA in people with type 1 diabetes and gastroparesis.

Diabetes Mellitus Type 2 (T2DM) is a metabolic disorder that is becoming increasingly common and can lead to a variety of problems. The purpose of this study was to explore the effects of calisthenic training exercises for twelve weeks on glucose levels, cardiovascular endurance, and body composition in people with type 2 diabetes.

Forty subjects, aged between 30 -75 years, diagnosed with type 2 diabetes, clinically stable participated. Participants were randomized (1:1) using computer-generated sealed envelopes with assessor blinding; one pre-intervention group switch altered final allocation. Participants were randomly allocated into two groups: intervention group (n = 21), calisthenic exercises for twelve weeks under the supervision of physiotherapist, and control group (n = 19), followed routine medical treatment. The glycated haemoglobin (HbA1c) and the fasting/random glucose levels were the primary outcomes, whereas the body mass index, blood pressure, and the 6-minute walk distance (6MWD) were the secondary. Statistical analysis paired and independent t-tests were utilized, and confidence intervals of 95% were utilized.

Total of 40 participants who met the inclusion criteria, ages between 30-75 years, 20 subjects in each interventional and control group were assigned. Result of the study indicate that the intervention group exhibited noteworthy enhancements in HbA1c (9.60 ± 1.25 to 6.54 ± 0.92, p < 0.001), body mass index (BMI) (26.51 ± 3.45 to 24.45 ± 2.98, p = 0.007), systolic blood pressure (136.38 ± 15.32 to 116.29 ± 12.47mmHg, p < 0.001), and six-minutes' walk distance (400.00 ± 48.60m to 517.14 ± 56.12m, p < 0.001). The results of this study indicate that structured calisthenic exercise is an efficient, low-cost, and easily accessible method for enhancing glycemic control and cardiovascular fitness in patients who have type 2 diabetes.

Multimorbidity in Type 2 Diabetes Mellitus (T2DM) profoundly influences disease progression and outcomes, yet conventional analytic approaches fail to capture its higher-order complexity.

Electronic health records from 6,960 inpatients with T2DM (2014-2023) were analyzed, identifying 24,481 hyperedges. Patients were stratified by HbA1c quartiles. A hypergraph framework was used to model higher-order multimorbidity, with eigenvector centrality (EVC), hyperedge impact, and quartile-based trajectories identifying dominant clusters and transitions.

Higher HbA1c was linked to younger age, male predominance, and greater smoking prevalence. Metabolic comorbidities-including dyslipidemia, metabolic liver disease, and vitamin D deficiency-became increasingly prevalent across glycemic strata, whereas hypertension and metabolic bone disease were more common in lower HbA1c. The multimorbidity network contracted as HbA1c rose, with fewer but more metabolically intensive hyperedges. "Dyslipidemia-metabolic liver disease" was the most prevalent cluster, while "hypertension-silent myocardial ischemia" had the highest impact. "Dyslipidemia-hyperuricemia" dominated late-stage metabolic impact, with vitamin D deficiency emerging as a key node in advanced networks.

Hypergraph analysis reveals T2DM multimorbidity progresses nonlinearly through distinct transition phases, marked by network consolidation and metabolic specialization. Critical transitions denote hepatic-metabolic destabilization, microvascular and neurovascular compromise, and cardiometabolic decompensation. Precision staging guided by network dynamics may enable phase-specific interventions to disrupt progression.

Gout and type 2 diabetes mellitus (T2DM) are prevalent metabolic disorders with a significant bidirectional association. The review article focuses on the interplay between serum uric acid and glucose/lipid metabolism, innate immunity, inflammation, and gut microbiota, proposing simultaneous treatment strategies. Gout, caused by monosodium urate crystal deposition due to hyperuricaemia, and T2DM, induced by high-fat, high-sugar diets disrupting metabolic balance, share common pathological mechanisms. Elevated uric acid levels contribute to lipid and glucose metabolic disorders, activate inflammatory pathways like the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome, and trigger innate immune responses. The gut microbiota also plays a significant role in both metabolic diseases, with dysbiosis affecting uric acid excretion and insulin resistance. This review article highlights promising therapeutic approaches, including the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors which reduce serum uric acid and lowers gout risk alongside glycaemic control. Additionally, targeting inflammatory pathways such as interleukin-1β (IL-1β) offers potential benefits for both conditions. Combined pharmacological therapies, dietary adjustments, and gut microbiota interventions present new directions for simultaneous management. This review article provides a comprehensive analysis of the links between gout and T2DM, offering novel insights for clinical practice and future research.

To conduct a randomized controlled trial (RCT) to assess whether patient-led insulin titration (intervention) compared with clinician-led insulin titration (control) resulted in improved glycemic management and pregnancy outcomes for individuals with gestational diabetes mellitus (GDM).

EMPOWER (Patient Versus Provider-Led Titration of Insulin for Glycemic Control in Gestational Diabetes) was a single-center, nonblinded RCT among individuals with GDM requiring insulin between 20 and 32 weeks of gestation that was conducted from October 19, 2023, to January 10, 2025. Intervention participants self-titrated long-acting insulin, which was started at 10 units nightly and decreased or increased by 2 units per fasting glucose above or below 70 and 95 mg/dL, respectively, every day. Control participants started an insulin dose with weekly titration at the clinician's discretion. The primary outcome was mean fasting glucose in the 36th week or the week before delivery for preterm deliveries. Secondary outcomes included pregnancy outcomes and patient-reported measures. With 80% power, two-sided α of 0.05, and 5% loss-to-follow-up, 56 individuals needed to be randomized to demonstrate at least a 15% difference in mean fasting glucose. Analysis was by intention to treat.

Of 89 individuals who were eligible during the study period, 56 consented and were randomized (29 intervention, 27 control). The median duration from starting insulin to delivery was 7.7 weeks. Patient-led insulin titration resulted in a similar mean fasting glucose before delivery compared with clinician-led titration (88.8 vs 90.3 mg/dL; β coefficient -1.50 mg/dL, 95% CI, -5.50 to 2.50) but resulted in more rapid achievement of fasting glucose below 95 mg/dL (mean 1.8 weeks vs 2.5 weeks; hazard ratio 1.48, 95% CI, 1.16 to 1.90). Patient-led titration was associated with a lower risk of macrosomia (6.9% vs 37.0%, relative risk 0.18, 95% CI, 0.04 to 0.84) and large-for-gestational-age (LGA) birth weight (3.3% vs 34.6%, relative risk 0.10, 95% CI, 0.08 to 0.12). Other pregnancy and patient-reported outcomes did not differ between the groups.

Patient-led insulin titration for GDM resulted in a similar mean fasting glucose compared with clinician-led insulin titration but was associated with more rapid achievement of glycemic control and a lower risk of macrosomia and LGA birth weight. These data support the need for larger patient-centered GDM treatment trials.

ClinicalTrials.gov, NCT05922033.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, is characterized by fatty deposits in the liver, with histologic features like alcohol-induced liver injury, without associated alcohol misuse. This condition is associated with other metabolic comorbidities, particularly obesity and insulin resistance. MASLD is also associated with the development of pregnancy-related complications such as gestational diabetes mellitus and hypertensive disorders of pregnancy. MASLD is one of the most common liver diseases today, with a prevalence of 14% in pregnant individuals.

The goal of this review was to explore the topic of MASLD with a discussion of its pathophysiology, diagnosis, clinical management, and complications related to pregnancy.

A literature search was conducted utilizing Rayyan to review 180 articles published between 2000 and 2024 for inclusion or exclusion in the review.

MASLD is an increasingly prevalent disease process likely underdiagnosed in pregnancy. Evidence suggests a synergistic pathway between obesity and the physiological changes of pregnancy, which can initiate or exacerbate liver steatosis. MASLD is associated with adverse outcomes in pregnancy and in the offspring of affected pregnancies.

Further research is needed to demonstrate optimal screening, diagnosis, and management in pregnancy. If detected early, early diabetes screening and low-dose aspirin may be appropriate, given the significant association with gestational diabetes and gestational hypertensive disorders. Patients should be counseled on the increased risk of maternal morbidity, preterm birth, miscarriage, macrosomia, pregnancy-induced hypertension, cesarean delivery, gestational diabetes, and metabolic disease in the offspring.

Chronic diabetic wounds are often complicated by biofilm-forming, antibiotic-resistant pathogens such as Staphylococcus aureus and Acinetobacter baumannii, which delay healing. This study evaluated the synergistic effects of gentamicin and imipenem in combination with fucoidan, a sulfated polysaccharide from brown seaweed, against dual-species biofilms in a diabetic rat wound model.

Methicillin-resistant S. aureus (MRSA) strain 6 and A. baumannii strain 1, isolated from diabetic foot ulcers, were used to establish dual-species biofilms in vitro and in vivo. Excisional wounds were created in male Wistar rats with streptozocin-induced type II diabetes and infected with the biofilms. Rats received daily treatments of gentamicin, imipenem, their combination, or the triple combination with fucoidan. Outcomes assessed included bacterial load (CFU/g), biofilm formation, expression of biofilm-related genes (icaA and bap by real-time PCR), wound size, and histological healing parameters.

The triple therapy demonstrated the strongest antibacterial effect, reducing bacterial load by more than 4 log₁₀ CFU/g compared to controls (p < 0.005). Real-time PCR revealed significant downregulation of icaA in S. aureus (threefold decrease) and bap in A. baumannii (fourfold decrease) relative to antibiotic-only groups (p < 0.005). Histology showed accelerated wound contraction and complete re-epithelialization by day 14 with the triple combination, whereas monotherapy or dual antibiotics led to delayed healing and persistent inflammation.

Fucoidan enhances the efficacy of gentamicin and imipenem against biofilm-associated infections and promotes diabetic wound healing. This combinatorial approach offers a promising strategy for managing chronic, biofilm-infected wounds and combating antibiotic resistance.

Ferroptosis, an iron-dependent cell death pathway driven by lipid peroxidation (LPO), is implicated in the pathogenesis of autoimmune diseases (AIDs). However, comprehensive clinical evidence establishing the association between specific LPO biomarkers and AIDs is lacking.

To systematically evaluate the clinical evidence for elevated LPO in major AIDs through a meta-analysis, focusing on key biomarkers including malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α).

We searched four databases for studies reporting serum, plasma, or urinary LPO levels in patients with AIDs and healthy controls. Standardized mean differences (SMDs) were pooled using a random-effects model.

Across 175 studies (8227 patients; 6866 controls), serum/plasma MDA levels were significantly elevated in all ten investigated AIDs: rheumatoid arthritis (RA) (SMD = 2.82), systemic sclerosis (SSc) (SMD = 2.08), Graves' disease (GD) (SMD = 1.92), Behçet's disease (BD) (SMD = 1.90), Crohn's disease (CD) (SMD = 1.71), multiple sclerosis (MS) (SMD = 1.52), psoriasis (PsO) (SMD = 1.44), ulcerative colitis (UC) (SMD = 1.32), systemic lupus erythematosus (SLE) (SMD = 1.20) and type 1 diabetes mellitus (T1DM) (SMD = 1.12). Disease-specific elevations were found for serum/plasma 8-iso-PGF2α and 4-hydroxynonenal in RA, urinary 8-iso-PGF2α in SSc and T1DM, and serum/plasma oxidized low-density lipoprotein in T1DM. MDA was higher in active or severe subgroups, with significant between-subgroup differences in GD and PsO.

This meta-analysis provides robust, large-scale clinical evidence that elevated lipid peroxidation is a common feature across diverse AIDs. These findings solidify the clinical relevance of ferroptosis, positioning LPO products as promising biomarkers and underscoring the therapeutic potential of targeting ferroptosis in autoimmune conditions.