A roadmap to achieve pharmacological precision medicine in diabetes

Current pharmacological treatment of diabetes is largely algorithmic. Other than for cardiovascular disease or renal disease, where sodium–glucose cotransporter 2 inhibitors and/or glucagon-like peptide-1 receptor agonists are indicated, the choice of treatment is based upon overall risks of harm or side effect and cost, and not on probable benefit. Here we argue that a more precise approach to treatment choice is necessary to maximise benefit and minimise harm from existing diabetes therapies. We propose a roadmap to achieve precision medicine as standard of care, to discuss current progress in relation to monogenic diabetes and type 2 diabetes, and to determine what additional work is required. The first step is to identify robust and reliable genetic predictors of response, recognising that genotype is static over time and provides the skeleton upon which modifiers such as clinical phenotype and metabolic biomarkers can be overlaid. The second step is to identify these metabolic biomarkers (e.g. beta cell function, insulin sensitivity, BMI, liver fat, metabolite profile), which capture the metabolic state at the point of prescribing and may have a large impact on drug response. Third, we need to show that predictions that utilise these genetic and metabolic biomarkers improve therapeutic outcomes for patients, and fourth, that this is cost-effective. Finally, these biomarkers and prediction models need to be embedded in clinical care systems to enable effective and equitable clinical implementation. Whilst this roadmap is largely complete for monogenic diabetes, we still have considerable work to do to implement this for type 2 diabetes. Increasing collaborations, including with industry, and access to clinical trial data should enable progress to implementation of precision treatment in type 2 diabetes in the near future. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains a slideset of the figures for download, which is available at 10.1007/s00125-022-05732-3

Co-Inoculation of Plant-Growth-Promoting Bacteria Modulates Physiological and Biochemical Responses of Perennial Ryegrass to Water Deficit

Perennial ryegrass is a forage commonly used in temperate regions for livestock feeding; however, its yield is affected by reduced biomass production under water deficit. In a previous study, three co-inoculations of beneficial bacteria were selected based on their ability to promote plant growth under reduced water availability. The aim of this work was to elucidate some mechanisms by which the selected bacteria can help improve the response of perennial ryegrass to water deficit. Ryegrass plants were inoculated with each of the co-inoculations (Herbaspirillum sp. AP02 Herbaspirillum sp. AP21; Herbaspirillum sp. AP02–Pseudomonas sp. N7; Herbaspirillum sp. AP21–Azospirillum brasilense D7) and subjected to water deficit for 10 days. Physiological and biochemical measurements were taken 10 days after stress and shortly after rehydration. The results showed that bacteria had a positive effect on shoot biomass production, dissipation of excess energy, and proline and chlorophyll pigments during the days of water deficit (p < 0.05). The leaf water status of the inoculated plants was 12% higher than that of the uninoculated control after rehydration. Two Herbaspirillum strains showed greater potential for use as biofertilizers that help ameliorate the effects of water deficit

Predictors of diabetes risk in urban and rural areas in Colombia

Background: Nutritional habits low in fruits and vegetables and sedentary lifestyle are associated with a higher risk of developing Type 2 Diabetes (T2D). However, it is important to assess differences between urban and rural areas. This study aimed to analyze the associations between the risk of developing T2D and setting in the Colombian north coast in 2017. Methods: This cross-sectional study included 1,005 subjects. Data was collected by interviewing self-identified members of an urban community and a rural-indigenous population. The interaction terms were evaluated as well as the confounders. Then, adjusted binary logistic regressions were used to estimate the odds ratio (OR) and 95% Confidence Intervals (CI). Results: subjects with a high risk of T2D are more likely to belong to the urban setting (OR = 1.908; 95%CI = 1.201-2.01) compared with those with lower T2D after adjusting for age, Body Mass Index (BMI), physical activity, history of high levels of glycemia, and diabetes in relatives. Conclusions: Urban communities are more likely to have T2D compared with rural-indigenous populations. These populations have differences from the cultural context, including personal, and lifestyle factors.Peer reviewe

Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population

Background Recent studies have implicated variants of the transcription factor 7-like 2 (TCF7L2) gene in genetic susceptibility to type 2 diabetes mellitus in several different populations. The aim of this study was to determine whether variants of this gene are also risk factors for type 2 diabetes development in a UK-resident South Asian cohort of Punjabi ancestry. Methods We genotyped four single nucleotide polymorphisms (SNPs) of TCF7L2 (rs7901695, rs7903146, rs11196205 and rs12255372) in 831 subjects with diabetes and 437 control subjects. Results The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR) of 1.31 (95% CI: 1.11 – 1.56, p = 1.96 × 10-3). For each variant, disease risk associated with homozygosity for the minor allele was greater than that for heterozygotes, with the exception of rs12255372. To determine the effect on the observed associations of including young control subjects in our data set, we reanalysed the data using subsets of the control group defined by different minimum age thresholds. Increasing the minimum age of our control subjects resulted in a corresponding increase in OR for all variants of the gene (p ≤ 1.04 × 10-7). Conclusion Our results support recent findings that TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups