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The 2021 statistics from the International Diabetes Federation reveals that approximately 537 million adults between the ages of 20 and 79 are currently coping with diabetes, highlighting the pressing demand for innovative treatments. To expedite this process, it is crucial to learn from previous failures in drug development. One established method for enhancing the biological, pharmacokinetic or the physicochemical properties of potent drug candidates is through the use of prodrugs. Prodrugs have demonstrated their effectiveness in surmounting challenges related to a drug's efficacy during the phases of drug research and development. This review distinctly emphasizes the role of the prodrug strategy in facilitating drug discovery to address concerns associated with diabetes mellitus (DM). It emphasizes the utilization of diverse prodrug approaches in the management of DM and the complications associated with it by categorizing them into ester/ether prodrugs, phosphonic diamide prodrugs, biguanide prodrugs, nitric oxide releasing prodrugs, mutual prodrugs, peptide-linked prodrugs, as well as different types of drug conjugate approaches. It specifically elaborates a range of prodrug systems developed between the years 2000 and 2023 for achieving effective drug delivery in the context of DM. [ABSTRACT FROM AUTHOR]

Diabetes related complications such as Diabetic Foot Ulcers (DFU) may necessitate recurrent hospitalisations and expensive treatments. Uncontrolled diabetes can result in severe DFUs, resulting in amputation of lower limbs or feet, prolonged debilitation and diminished quality of life. Early diagnosis and proactive management are reported to signifi- cantly enhance the prognosis and reduce the onset of further complications. In this study, research works on developing clinical decision support systems (CDSS) for the identification and segmentation of DFU are systematically reviewed. The techniques employed range from traditional image processing techniques to approaches based on deep learning (DL). A taxonomy of DFU CDSSs is presented, categorised into two groups: RGB-based techniques and thermal imaging-based approaches. To the best of our knowledge, this is the first attempt at a comprehensive study of CDSSs for DFU related investigative tasks, based on different imaging modalities. We also delve into the difficulties experienced in the process of creating efficient, reliable, and accurate models for the early detection of DFU, and highlight the vast potential for further research in this emerging domain. [ABSTRACT FROM AUTHOR]

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Purpose: Neonatal diabetes mellitus (NDM) is caused by mutations in the genes responsible for pancreatic β cell mass or function. This study aimed to screen the mutations in the KCNJ11, ABCC8, and INS genes in a Chinese patient with clinical features of NDM. Methods: The entire coding sequence and exon/intron boundaries of KCNJ11, ABCC8, and INS genes were detected by Sanger sequencing. The pathogenicity of the mutation was determined by using online prediction programs SIFT and Mutation Taser. The conformational alterations which contribute to the change of protein function were analyzed at the structural level. Results: A novel mutation L35Q (B11) of the INS gene was discovered in the patient. As L35 residue contributes to its hydrophobic core of the protein, the L35Q substitution is predicated to affect B19-A20 disulfide bond and therefore disrupt the folding of the proinsulin, which ultimately results in beta cell apoptosis by inducing ER stress. Conclusions: This case could help us understand the role of the INS mutation in the development of diabetes. [ABSTRACT FROM AUTHOR]

Aims: This study was designed to compare the risk of long-term health outcomes, including microvascular, macrovascular complications and mortality, across 4 cohorts: triple-goal, dual-goal, single-goal, and no-goal achievers.Methods: A retrospective cohort of 53,120 patients with T2DM were identified (97.51% male, 61.49% whites) from the Veterans Affairs (VA) electronic medical records VISN 16 data warehouse (2004-2010). Propensity score weight (PSW) was used to balance demographic characteristics and complication history at baseline. The PSW adjusted hazard ratios (aHR) from Cox proportional hazard models were used to compare complications and all-cause mortality over an average of 4 years of follow-up.Results: At baseline, 25.43% (13,507) patients achieved triple-goal, while 41.36% (21,972) and 26.37% (14,010) patients achieved dual-goal and single-goal, respectively. During the follow-up period, triple-goal achievement was associated with risk reductions of complications and all-cause mortality when compared to all other groups of achieving dual or single-goal. Across different combinations of dual-goal achievement, the cohort with LDL-C goal achievement had lower risk of complication events and mortality, compared to those that achieved other goals but failed to reach LDL-C goal.Conclusions: Achievement of triple-goal was associated with better health outcomes among veterans with T2DM compared to those that did not, while LDL-C has more weight of influence. Multi-faceted treatment strategies targeting hypertension, hyperglycemia and hyperlipidemia may improve health outcome in veterans with T2DM. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Notoriously, the tropical island of Mauritius has one of the highest prevalence of diabetes worldwide and the economic burden associated with it is alarming. The use of native remedies (NRs) is well anchored in the local culture and it continues to be the cornerstone of therapy for diabetic patients. However, there is currently a dearth of updated primary data on NRs used by Mauritians against diabetes and diabetes related complications (DRCs). This study was therefore designed to record, analyze and document orally transmitted ethnopharmacological knowledge from diabetic patients and traditional medicine practitioners (TMPs) in Mauritius concerning NRs commonly used against diabetes and DRCs which might open new avenues to initiate novel antidiabetic drugs discovery. Materials and methods: Data was collected following interviews from diabetic patients (n=328) and TMPs (n=20). Eleven quantitative indexes, namely informant consensus factor (FIC), fidelity level (FL), use value (UV), relative frequency of citation (RFC), relative importance (RI), cultural importance index (CII), index of agreement on remedies (IAR), cultural agreement index (CAI), quality use value (QUV), quality use agreement value (QUAV) and ethnobotanicity index (EI) were calculated. Statistical analysis such as Pearson correlation and Chi-squared test were performed to determine any association. Results: A total of 111 plant species distributed over 56 families, 30 polyherbal formulations and 16 animal species were documented to be traditionally used against diabetes and DRCs. For the first time 8 endemic plants have been recorded to be used against diabetes and DRCs from Mauritius. The most encountered medicinal plant family was Asteraceae. According to the EI, 16.2% of the native plants in Mauritius were used against diabetes and DRCs. As far as we know, Vangueria madagascariensis, Apium graveolens, Petroselinum crispum and Rubus alceifolius with high RFC values are recorded against diabetes and DRCs for the first time. Sociodemographic characteristics (age, gender, income, religious belief, education and residence) were found to significantly (p<0.05) influence the use of NRs. The average FIC for all ailments for plant and animal products were 0.94 and 0.87 respectively. Bryophyllum pinnatum, a native plant to Mauritius scored a high FL value (100%) used against diabetic neuropathy, Allium sativum had the highest RI value (2.00) due to its versatility, Aloe vera had the highest RFC (0.61), the CII (0.640) and the highest CAI value (0.635), Psidium guajava had the highest QUAV (0.961) which indicates its high bioactivity and Allium cepa was reported as the most effective plant species (QUV=0.965). According to UV, the most important species was Morinda citrifolia (1.21). Panoply of animal products were reported whereby fish (39.7%) was recorded as the most utilised zootherapy and Salmo salar scored the highest FL (100%) for diabetes. Some animal species (n=14) not previously documented against diabetes and DRCs are reported in the present study. Conclusion: Our present investigation revealed that the use of NRs constitutes the common legacy of Mauritians and despite the penetration of allopathic medicine; NRs continue to play a crucial role in the primary health care system of Mauritius. To this effect, it is of uttermost importance to record this knowledge before it disappears. In addition, further experimental investigations are required to elucidate the pharmacological properties of the reported medicinal flora and fauna of Mauritius. [ABSTRACT FROM AUTHOR]

Methodology: This paper illustrates the use of multistate approach to product limit method developed by Islam (1994) under the competing risk framework for diabetes related complications among diabetic patient. The method takes into account of the censored and uncensored survivorship functions separately. To identify the risk factor for the diabetic related complications, an exponential regression model under the competing risk framework were used. Since more than one complication could occur, thus, only the incidences of the first complication among the diabetic patient were considered in the study. The complications are cardiovascular, peripheral vascular, cerebrovascular, ophthalmic, neurologic and renal disease complication. [ABSTRACT FROM AUTHOR]