Type 2 diabetes metabolomics score and risk of progression to type 2 diabetes among women with a history of gestational diabetes mellitus

Diabetes Care

OBJECTIVE Breastfeeding duration is inversely associated with risks of cardiovascular disease (CVD) and type 2 diabetes in parous women. However, the association among women at high risk, including women with type 2 diabetes or gestational diabetes (GDM) is unclear. RESEARCH DESIGN AND METHODS We included 15,146 parous women with type 2 diabetes from the Nurses’ Health Study I and II (NHS, NHS II) and 4,537 women with a history of GDM from NHS II. Participants reported history of breastfeeding via follow-up questionnaires. Incident CVD by 2017 comprised stroke or coronary heart disease (CHD: myocardial infarction, coronary revascularization). Adjusted hazard ratios (aHRs) and 95% CIs were estimated using Cox models. RESULTS We documented 1,159 incident CVD cases among women with type 2 diabetes in both cohorts during …

Metabolism

BackgroundMetabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion.MethodsThe study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was …

Clinical Pediatrics

Dr. Lester F. Soyka: E. M., a 13-year-old girl, was referred to the Massachusetts General Hospital because of uncontrolled hyper-tension. She was in apparent good health until four years ago when she had an episode of dysuria and pyuria diagnosed as cystitis and treated with Furadantin. She had two subsequent attacks three years ago and one year ago similarly treated. She seemed well until six weeks prior to admission when gross hematuria developed with no associated symptoms and no previous history of recent upper respiratory infection. Penicillin was started. In the next few days she developed headache, abdominal cramps, and anorexia. On admission to another hospital it was found that her blood pressure was 270/190, there was marked arteriolar spasm on funduscopy, and her urine was loaded with red and white blood cells with no casts. Intravenous and retrograde pyelography showed a shrunken …

Healthy blood vessels supply neurons to preserve metabolic function. In blinding proliferative retinopathies (PRs), pathological neovascular tufts often emerge in lieu of needed physiological revascularization of the ischemic neuroretina. Here we show that metabolic shifts in the neurovascular niche define angiogenic fate. Fatty acid oxidation (FAO) metabolites accumulated in human and murine retinopathy samples. Neovascular tufts with a distinct single-cell transcriptional signature highly expressed FAO enzymes. The deletion of Sirt3, an FAO regulator, shifted the neurovascular niche metabolism from FAO to glycolysis and suppressed tuft formation. This metabolic transition increased Vegf expression in astrocytes and reprogrammed pathological EC to a physiological phenotype, hastening vascular regeneration of the ischemic retina. Hence, strategies to change the metabolic environment of vessels could promote a regenerative phenotype in vascular diseases.

EBioMedicine

BackgroundLung function trajectories (LFTs) have been shown to be an important measure of long-term health in asthma. While there is a growing body of metabolomic studies on asthma status and other phenotypes, there are no prospective studies of the relationship between metabolomics and LFTs or their genomic determinants.MethodsWe utilized ordinal logistic regression to identify plasma metabolite principal components associated with four previously-published LFTs in children from the Childhood Asthma Management Program (CAMP) (n = 660). The top significant metabolite principal component (PCLF) was evaluated in an independent cross-sectional child cohort, the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) (n = 1151) and evaluated for association with spirometric measures. Using meta-analysis of CAMP and GACRS, we identified associations between PCLF and microRNA, and …

Journal of Allergy and Clinical Immunology

BackgroundThere are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations.ObjectiveWe sought to identify metabolites unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort, the Boston Birth Cohort.MethodsMass spectrometry–based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (n = 811). FA was diagnosed according to clinical symptoms consistent with an acute hypersensitivity reaction at food ingestion and food specific-IgE > 0.35 kU/L. Asthma was defined on the basis of physician diagnosis. Generalized estimating equations were applied to analyze metabolomic associations with FA and asthma, adjusting for potential confounders.ResultsDuring a …

EClinicalMedicine

BackgroundUltra-processed foods (UPFs) are emerging as a risk factor for colorectal cancer (CRC), yet how post-diagnostic UPF intake may impact CRC prognosis remains unexplored.MethodsData collected from food frequency questionnaires were used to estimate intakes of total UPFs and UPF subgroups (serving/d) at least 6 months but less than 4 years post-diagnosis among 2498 patients diagnosed with stages I–III CRC within the Nurses' Health Study and Health Professionals Follow-up Study during 1980–2016. Hazard ratios (HR) and 95% confidence intervals (CIs) of all-cause, CRC- and cardiovascular disease (CVD)-specific mortality in association with UPF consumption were estimated using an inverse probability weighted multivariable Cox proportional hazards regression model, adjusted for confounders.FindingsThe mean (SD) age of patients at diagnosis was 68.5 (9.4) years. A total of 1661 deaths …

The American Journal of Clinical Nutrition

BackgroundThe health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood.ObjectivesOur goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors.MethodsA total of 400 participants (200 from each study group), aged 55–75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry …

Med

BackgroundA healthy lifestyle is associated with a lower premature mortality risk and with longer life expectancy. However, the metabolic pathways of a healthy lifestyle and how they relate to mortality and longevity are unclear. We aimed to identify and replicate a healthy lifestyle metabolomic signature and examine how it is related to total and cause-specific mortality risk and longevity.MethodsIn four large cohorts with 13,056 individuals and 28-year follow-up, we assessed five healthy lifestyle factors, used liquid chromatography mass spectrometry to profile plasma metabolites, and ascertained deaths with death certificates. The unique healthy lifestyle metabolomic signature was identified using an elastic regression. Multivariable Cox regressions were used to assess associations of the signature with mortality and longevity.FindingsThe identified healthy lifestyle metabolomic signature was reflective of lipid …

Journal of Allergy and Clinical Immunology

MethodsUntargeted metabolomic profiling was conducted on plasma samples from 4 timepoints during a longitudinal peanut OIT interventional trial in children ages 7-18. After OIT, participants were challenged before and after a 4-week avoidance period and categorized as either having persistent protection (sustained unresponsiveness (SU)) or loss of protection (transient desensitization (TD)). Using linear and logistic regression and time series analyses, we identified changes in metabolites and pathways associated with (1) OIT over time, and (2) differences between SU and TD participants.ResultsWe identified decreases in arachidonic acid (p= 1.3 e-23) and linoleic acid (p= 1.0 e-04) pathways during OIT. Comparing SU versus TD revealed differing concentrations of bile acid (p= 3.7 e-08), arachidonic acid (p= 3.2 e-09), and histidine pathways. Notably, the bile acid metabolite, lithocholate (3.48 [1.53, 9.24], p …

Cell Metabolism

Common genetic variants in glucokinase regulator (GCKR), which encodes GKRP, a regulator of hepatic glucokinase (GCK), influence multiple metabolic traits in genome-wide association studies (GWASs), making GCKR one of the most pleiotropic GWAS loci in the genome. It is unclear why. Prior work has demonstrated that GCKR influences the hepatic cytosolic NADH/NAD+ ratio, also referred to as reductive stress. Here, we demonstrate that reductive stress is sufficient to activate the transcription factor ChREBP and necessary for its activation by the GKRP-GCK interaction, glucose, and ethanol. We show that hepatic reductive stress induces GCKR GWAS traits such as increased hepatic fat, circulating FGF21, and circulating acylglycerol species, which are also influenced by ChREBP. We define the transcriptional signature of hepatic reductive stress and show its upregulation in fatty liver disease and …

Cancer Research

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of all cancer types. A key — yet poorly understood — facet in the disease state is cachexia, a multi-organ pathological state characterized by physical wasting and tissue catabolism. It occurs in 80% of PDAC patients, and to date there are no preventative or early detection methods. Cachexia leads to limited tolerance to anti-cancer therapy and contributes to disease lethality. Here, we present the first-of-its-kind systemic metabolomic analysis across cachectic stages to better understand disease progression. We used the well-established mutant KRASG12D(LSL/+) mutant p53 inducible mouse model of PDAC. Model physiology faithfully recaptures human cachexia: we observe progressive overall weight loss as well as loss of skeletal muscle and adipose tissue. As with human disease, weight loss occurs prior to loss of appetite in the animals …

The American Journal of Clinical Nutrition

BackgroundDistinct circulating bile acid (BA) subtypes may play roles in regulating lipid homeostasis and atherosclerosis.ObjectivesWe investigated whether changes in circulating BA subtypes induced by weight-loss dietary interventions were associated with improved lipid profiles and atherosclerotic cardiovascular disease (ASCVD) risk estimates.MethodsThis study included adults with overweight or obesity (n=536) who participated in a randomized weight-loss diet intervention trial. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 months after weight-loss diet interventions. The ASCVD risk estimates were calculated by the validated equations.ResultsAt baseline, higher levels of specific BA subtypes were related to higher levels of atherogenic VLDL lipid subtypes and ASCVD risk estimates. Weight-loss diet-induced decreases in …

Cardiovascular diabetology

BackgroundLegume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume consumption, and subsequently investigate its potential association with the incidence of T2D and CVD.MethodsThe current cross-sectional and longitudinal analysis was conducted in 1833 PREDIMED study participants (mean age 67 years, 57.6% women) with available baseline metabolomic data. A subset of these participants with 1-year follow-up metabolomics data (n = 1522) was used for internal validation. Plasma metabolites were assessed through liquid chromatography-tandem mass spectrometry. Cross-sectional associations between 382 …

MethodsWe included 911 participants from the San Juan Overweight Adult Longitudinal Study, a 3-year prospective cohort of overweight Puerto Ricans. At baseline, using LC-MS, we quantified metabolites from saliva (n= 635) and plasma (n= 1,051). We used elastic net regression with 10-fold cross-validation to identify features from saliva, plasma, and saliva and plasma (multi-fluid) that were predictive of BMI and WC. We used Cox-proportional hazard models to evaluate associations between metabolomic profiles and diabetes progression, adjusting for age, sex, socioeconomic factors, lifestyle, and medication use.ResultsFor BMI metabolomic profiles, we identified 207 metabolites in plasma, 118 metabolites in saliva, and 225 in the multi-fluid profile. For WC, we identified 157, 89, and 210 metabolites for saliva, plasma, and multi-fluid profiles, respectively. Highly positively weighted metabolites across all BMI and WC metabolomic profiles included those in pathways of alanine and aspartate metabolism, purine metabolism, and sphingomyelins. Each SD increase in saliva, but not plasma or multi-fluid, metabolic profile of BMI was significantly associated with all stages of diabetes progression. Saliva, but not plasma or multi-fluid, metabolomic profile of WC was significantly associated with progression from pre-diabetes to T2D. All associations became stronger after further adjustment for anthropometric measures of BMI and WC.ConclusionSaliva is an underexplored and easily accessible biofluid to measure metabolites that are reflective of adiposity measures. Validation in future studies will confirm our findings that saliva, plasma, and multi-fluid …

Metabolism

BackgroundMetabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion.MethodsThe study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was …

Nature medicine

Multiple dietary patterns have been associated with different diseases; however, their comparability to improve overall health has yet to be determined. Here, in 205,852 healthcare professionals from three US cohorts followed for up to 32 years, we prospectively assessed two mechanism-based diets and six diets based on dietary recommendations in relation to major chronic disease, defined as a composite outcome of incident major cardiovascular disease (CVD), type 2 diabetes and cancer. We demonstrated that adherence to a healthy diet was generally associated with a lower risk of major chronic disease (hazard ratio (HR) comparing the 90th with the 10th percentile of dietary pattern scores = 0.58–0.80). Participants with low insulinemic (HR = 0.58, 95% confidence interval (CI) = 0.57, 0.60), low inflammatory (HR = 0.61, 95% CI = 0.60, 0.63) or diabetes risk-reducing (HR = 0.70, 95% CI = 0.69 …

The United States is a leading consumer of ultraprocessed foods (UPFs) globally, with a staggering 55% of adults’ energy intake coming from these products [1]. In addition to enhanced processing techniques, Nova-defined UPFs also contain cosmetic additives to enhance palatability, profitability, and shelf-life, at no nutritional value [2]. Recent meta-analyses documented significant adverse associations of UPFs with diabetes [3] and cardiovascular disease [4]. Building on this growing body of literature, Vitale et al.[5] conducted an comprehensive systematic review, highlighting the following 3 salient conclusions: 1) heterogeneity in risk estimates is not as profound as some UPF industry and other stakeholders argue; 2) UPF classification should evolve to reflect both food processing and nutritional value; and 3) although the quality of UPF research can (and should) be improved on, limitations of the current evidence …

Diabetes/Metabolism Research and Reviews

Background/Aim Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta‐cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to identify autoantibody‐positive individuals increases, a rise in presymptomatic type 1 diabetes individuals seeking medical attention is expected. Current guidance on how to monitor these individuals in a safe but minimally invasive way is limited. This article aims to provide clinical guidance for monitoring individuals with presymptomatic type 1 diabetes to reduce the risk of diabetic ketoacidosis (DKA) at diagnosis. Methods Expert consensus was obtained from members of the Fr1da, GPPAD, and INNODIA consortia, three European diabetes research groups. The guidance covers both specialist and primary care follow‐up strategies. Results The guidance outlines …

Diabetes/Metabolism Research and Reviews

Background/Aim Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta‐cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to identify autoantibody‐positive individuals increases, a rise in presymptomatic type 1 diabetes individuals seeking medical attention is expected. Current guidance on how to monitor these individuals in a safe but minimally invasive way is limited. This article aims to provide clinical guidance for monitoring individuals with presymptomatic type 1 diabetes to reduce the risk of diabetic ketoacidosis (DKA) at diagnosis. Methods Expert consensus was obtained from members of the Fr1da, GPPAD, and INNODIA consortia, three European diabetes research groups. The guidance covers both specialist and primary care follow‐up strategies. Results The guidance outlines …

Diabetes/Metabolism Research and Reviews

Background/Aim Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta‐cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to identify autoantibody‐positive individuals increases, a rise in presymptomatic type 1 diabetes individuals seeking medical attention is expected. Current guidance on how to monitor these individuals in a safe but minimally invasive way is limited. This article aims to provide clinical guidance for monitoring individuals with presymptomatic type 1 diabetes to reduce the risk of diabetic ketoacidosis (DKA) at diagnosis. Methods Expert consensus was obtained from members of the Fr1da, GPPAD, and INNODIA consortia, three European diabetes research groups. The guidance covers both specialist and primary care follow‐up strategies. Results The guidance outlines …

Diabetes/Metabolism Research and Reviews

Aims Infections are proposed risk factors for type 1 diabetes in children. We examined whether a diagnosis of infectious disease also confers an increased risk of latent autoimmune diabetes in adults (LADA). Materials and methods We used data from a population‐based Swedish case‐control study with incident cases of LADA (n = 597) and matched controls (n = 2386). The history of infectious disease was ascertained through national and regional patient registers. We estimated adjusted odds ratios (OR) with 95% confidence intervals for ≥1 respiratory (any/upper/lower), gastrointestinal, herpetic, other or any infectious disease episode, or separately, for 1 and ≥2 infectious disease episodes, within 0–1, 1–3, 3–5 and 5–10 years before LADA diagnosis/matching. Stratified analyses were performed on the basis of HLA risk genotypes and Glutamic acid decarboxylase antibodies (GADA) levels. Results …

Diabetes/Metabolism Research and Reviews

Background Several metabolites are individually related to incident type 2 diabetes (T2D) risk. We prospectively evaluated a novel T2D‐metabolite pattern with a risk of progression to T2D among high‐risk women with a history of gestational diabetes mellitus (GDM). Methods The longitudinal Nurses' Health Study II cohort enroled 116,429 women in 1989 and collected blood samples from 1996 to 1999. We profiled plasma metabolites in 175 incident T2D cases and 175 age‐matched controls, all with a history of GDM before the blood draw. We derived a metabolomics score from 21 metabolites previously associated with incident T2D in the published literature by scoring according to the participants' quintile (1–5 points) of each metabolite. We modelled the T2D metabolomics score categorically in quartiles and continuously per 1 standard deviation (SD) with the risk of incident T2D using conditional logistic …

Diabetes/Metabolism Research and Reviews

Aims Sodium–glucose cotransporter‐2 inhibitors (SGLT2is) are proposed to alleviate the development of inflammatory eye diseases. However, the association between SGLT2i and retinal vascular occlusion remains unclear. Therefore, this study aims to explore the effects of SGLT2i on the incidence of retinal vascular occlusion. Materials and Methods This retrospective cohort study analysed electronic medical records data from the largest multi‐institutional database in Taiwan. Individuals who initiated SGLT2is and dipeptidyl peptidase 4 inhibitors (DPP4is) between 2016 and 2019 were included in our analysis. To conduct a homogenous comparison, inverse probability of treatment weighting with propensity scoring was employed. The primary outcome was retinal vascular occlusion, and the secondary outcomes were retinal vascular occlusion‐related complications (macular oedema, vitreous haemorrhage …

Diabetes/Metabolism Research and Reviews

Aims Given the increasing number of individuals developing metabolic dysfunction‐associated steatotic liver disease (MASLD) and the low rate of those with progressive liver disease, there is a pressing need to conceive affordable biomarkers to assess MASLD in general population settings. Herein, we aimed to investigate the performance of the ultrasound‐derived fat fraction (UDFF) for hepatic steatosis in high‐risk individuals. Methods A total of 302 Europeans with obesity, type 2 diabetes, or a clinical history of hepatic steatosis were included in the analyses. Clinical, laboratory, and imaging data were collected using standardized procedures during a single screening visit in Rome, Italy. Hepatic steatosis was defined by controlled attenuation parameter (CAP) or ultrasound‐based Hamaguchi's score. UDFF performance for hepatic steatosis was estimated by the area under the receiver operating characteristic …

Diabetes/Metabolism Research and Reviews

Aims To evaluate the impact of adherence to glucagon like peptide‐1 receptor agonists (GLP1‐RA) and sodium‐glucose transporter two inhibitors (SGLT2‐I) on clinical outcomes and costs in patients with type 2 diabetes mellitus (T2DM). Materials and Methods The 121,115 residents of the Lombardy Region (Italy) aged ≥40 years newly treated with metformin during 2007–2015 were followed to identify those who started therapy with GLP1‐RA or SGLT2‐I. Adherence to drug therapy over the first year was defined as the proportion of days covered >80%. Within each drug class, for each adherent patient, one non‐adherent patient was matched for age, sex, duration, adherence to metformin treatment and propensity score. The primary clinical outcome was a composite of insulin initiation, hospitalisation for micro‐ and macrovascular complications and all‐cause mortality after the first year of drug treatment. Costs …

Diabetes/Metabolism Research and Reviews

Background Diabetes mellitus (DM) is associated with structural grey matter alterations in the brain, including changes in the somatosensory and pain processing regions seen in association with diabetic peripheral neuropathy. In this case‐controlled biobank study, we aimed to ascertain differences in grey and white matter anatomy in people with DM compared with non‐diabetic controls (NDC). Methods This study utilises the UK Biobank prospective, population‐based, multicentre study of UK residents. Participants with diabetes and age/gender‐matched controls without diabetes were selected in a three‐to‐one ratio. We excluded people with underlying neurological/neurodegenerative disease. Whole brain, cortical, and subcortical volumes (188 regions) were compared between participants with diabetes against NDC corrected for age, sex, and intracranial volume using univariate regression models, with …

Diabetes/Metabolism Research and Reviews

Aims Determining diabetes type in children has become increasingly difficult due to an overlap in typical characteristics between type 1 diabetes (T1D) and type 2 diabetes (T2D). The Diabetes Study in Children of Diverse Ethnicity and Race (DISCOVER) programme is a National Institutes of Health (NIH)‐supported multicenter, prospective, observational study that enrols children and adolescents with non‐secondary diabetes. The primary aim of the study was to develop improved models to differentiate between T1D and T2D in diverse youth. Materials and Methods The proposed models will evaluate the utility of three existing T1D genetic risk scores in combination with data on islet autoantibodies and other parameters typically available at the time of diabetes onset. Low non‐fasting serum C‐peptide (<0.6 nmol/L) between 3 and 10 years after diabetes diagnosis will be considered a biomarker for T1D as it …

Diabetes/Metabolism Research and Reviews

Background/Aim Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta‐cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to identify autoantibody‐positive individuals increases, a rise in presymptomatic type 1 diabetes individuals seeking medical attention is expected. Current guidance on how to monitor these individuals in a safe but minimally invasive way is limited. This article aims to provide clinical guidance for monitoring individuals with presymptomatic type 1 diabetes to reduce the risk of diabetic ketoacidosis (DKA) at diagnosis. Methods Expert consensus was obtained from members of the Fr1da, GPPAD, and INNODIA consortia, three European diabetes research groups. The guidance covers both specialist and primary care follow‐up strategies. Results The guidance outlines …

Diabetes/metabolism research and reviews

Aims Offloading mechanical tissue stress is arguably the most important of multiple interventions needed to heal diabetes‐related foot ulcers. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence‐based guideline on offloading interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline. Materials and Methods We followed the GRADE approach by devising clinical questions and important outcomes in the PICO (Patient‐Intervention‐Control‐Outcome) format, undertaking a systematic review and meta‐analyses, developing summary of judgement tables and writing recommendations and rationales for each question. Each recommendation is based on the evidence found in the systematic review, expert opinion where evidence was not available, and a careful weighing of GRADE summary of judgement items including …

Diabetes/Metabolism Research and Reviews

Multiple disciplines are involved in the management of diabetes‐related foot disease and a common vocabulary is essential for clear communication. Based on the systematic reviews of the literature that form the basis of the International Working Group on the Diabetic Foot (IWGDF) Guidelines, the IWGDF has developed a set of definitions and criteria for diabetes‐related foot disease. This document describes the 2023 update of these definitions and criteria. We suggest these definitions be used consistently in both clinical practice and research, to facilitate clear communication with people with diabetes‐related foot disease and between professionals around the world.

Diabetes/Metabolism Research and Reviews

Background/Aim Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta‐cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to identify autoantibody‐positive individuals increases, a rise in presymptomatic type 1 diabetes individuals seeking medical attention is expected. Current guidance on how to monitor these individuals in a safe but minimally invasive way is limited. This article aims to provide clinical guidance for monitoring individuals with presymptomatic type 1 diabetes to reduce the risk of diabetic ketoacidosis (DKA) at diagnosis. Methods Expert consensus was obtained from members of the Fr1da, GPPAD, and INNODIA consortia, three European diabetes research groups. The guidance covers both specialist and primary care follow‐up strategies. Results The guidance outlines …

Diabetes/Metabolism Research and Reviews

Background Several metabolites are individually related to incident type 2 diabetes (T2D) risk. We prospectively evaluated a novel T2D‐metabolite pattern with a risk of progression to T2D among high‐risk women with a history of gestational diabetes mellitus (GDM). Methods The longitudinal Nurses' Health Study II cohort enroled 116,429 women in 1989 and collected blood samples from 1996 to 1999. We profiled plasma metabolites in 175 incident T2D cases and 175 age‐matched controls, all with a history of GDM before the blood draw. We derived a metabolomics score from 21 metabolites previously associated with incident T2D in the published literature by scoring according to the participants' quintile (1–5 points) of each metabolite. We modelled the T2D metabolomics score categorically in quartiles and continuously per 1 standard deviation (SD) with the risk of incident T2D using conditional logistic …

Diabetes/Metabolism Research and Reviews

Aims Determining diabetes type in children has become increasingly difficult due to an overlap in typical characteristics between type 1 diabetes (T1D) and type 2 diabetes (T2D). The Diabetes Study in Children of Diverse Ethnicity and Race (DISCOVER) programme is a National Institutes of Health (NIH)‐supported multicenter, prospective, observational study that enrols children and adolescents with non‐secondary diabetes. The primary aim of the study was to develop improved models to differentiate between T1D and T2D in diverse youth. Materials and Methods The proposed models will evaluate the utility of three existing T1D genetic risk scores in combination with data on islet autoantibodies and other parameters typically available at the time of diabetes onset. Low non‐fasting serum C‐peptide (<0.6 nmol/L) between 3 and 10 years after diabetes diagnosis will be considered a biomarker for T1D as it …

Diabetes/Metabolism Research and Reviews

Aims Our aims were, in the setting of type 2 diabetes mellitus (T2DM) in pregnancy, to investigate the association of polycystic ovary syndrome (PCOS) with perinatal outcomes and to examine whether treatment with metformin had a differential effect in those with and without PCOS. Materials and Methods We performed a retrospective cohort study using the metformin in women with type 2 diabetes in pregnancy (MiTy) trial data. We examined differences in maternal and neonatal outcomes among MiTy participants with and without PCOS using linear and logistic regression to adjust for potential confounders. We additionally examined the relative difference in the effect of metformin treatment on pregnancy outcomes among MiTy participants with PCOS versus those without PCOS. Results Among women with T2DM in pregnancy, PCOS was significantly associated with higher excess gestational weight gain …

Diabetes/Metabolism Research and Reviews

Aims Determining diabetes type in children has become increasingly difficult due to an overlap in typical characteristics between type 1 diabetes (T1D) and type 2 diabetes (T2D). The Diabetes Study in Children of Diverse Ethnicity and Race (DISCOVER) programme is a National Institutes of Health (NIH)‐supported multicenter, prospective, observational study that enrols children and adolescents with non‐secondary diabetes. The primary aim of the study was to develop improved models to differentiate between T1D and T2D in diverse youth. Materials and Methods The proposed models will evaluate the utility of three existing T1D genetic risk scores in combination with data on islet autoantibodies and other parameters typically available at the time of diabetes onset. Low non‐fasting serum C‐peptide (<0.6 nmol/L) between 3 and 10 years after diabetes diagnosis will be considered a biomarker for T1D as it …

Diabetes/Metabolism Research and Reviews

Context Mortality in type 2 diabetes is twice that of the normoglycemic population. Unravelling biomarkers that identify high‐risk patients for referral to the most aggressive and costly prevention strategies is needed. Objective To validate in type 2 diabetes the association with all‐cause mortality of a 14‐metabolite score (14‐MS) previously reported in the general population and whether this score can be used to improve well‐established mortality prediction models. Methods This is a sub‐study consisting of 600 patients from the “Sapienza University Mortality and Morbidity Event Rate” (SUMMER) study in diabetes, a prospective multicentre investigation on all‐cause mortality in patients with type 2 diabetes. Metabolic biomarkers were quantified from serum samples using high‐throughput proton nuclear magnetic resonance metabolomics. Results In type 2 diabetes, the 14–MS showed a significant (p < 0.0001 …

Diabetes/Metabolism Research and Reviews

Aims We aimed to examine the longitudinal associations of birth weight with plasma metabolites in adulthood, and further quantify the proportions of the links between birth weight and incident adult type 2 diabetes (T2D) that were mediated by plasma metabolites. Materials and Methods A total of 62,033 participants with complete nuclear magnetic resonance metabolomics and birth weight data from the UK Biobank were included in this study. Linear regression was used to assess the associations between birth weight and metabolites. Cox regression was used to estimate hazard ratios for T2D associated with metabolites. We further performed mediation analyses to estimate the extent to which metabolites might mediate the association between birth weight and T2D risk. Results Low birth weight was associated with the adverse metabolic responses across multiple metabolic pathways, including lipoprotein …