To investigate the association of health literacy, illness perceptions, and beliefs about medications on medication-taking behavior among first- and second-generation Australians of Chinese heritage living with type 2 diabetes mellitus (T2DM).

A nationwide cross-sectional online survey of (N = 455) of whom 196 responded, was conducted among adults (≥18 years) with T2DM of Chinese heritage residing in Australia. Participants were recruited via direct invitation (national registry and specialist clinic). Data collection utilized four validated questionnaires: The Brief Medication Questionnaire, Beliefs about Medicines Questionnaire Specific (BMQ-Specific), Brief Illness Perception 9 Questionnaire (BIPQ), and a 12-item short-form health literacy (HL) questionnaire (HLS-SF12). Bivariate and multivariate analyses were conducted to explore the factors associated with medication-taking.

Overall, 27 % of participants reported missing diabetes medication(s) in the past week, with access barriers most cited (38 %), followed by belief (27 %) and recall (24 %) barriers. Median scores for health literacy, illness perception and beliefs about medications showed problems with health literacy (General Health Literacy Index, median [IQR] =31.94 [26.39ꟷ38.89], a moderate threat to illness perception (BIPQ:= 38.56 ± 10.52) and higher perceived necessity of taking diabetes medications relative to concern (BMQ-Specific Necessity: = 3.80 [3.20-4.20]; BMQ-Specific Concern: = 3.00 [2.50-3.67]). Better medication-taking was seen in people with high necessity beliefs and with low concerns in the use of medications. Health literacy and illness perceptions were not significantly associated with medication-taking behavior.

Medication beliefs play a role in sub-optimal medication-taking behavior among Chinese adults with T2DM. Increased attention needs to be placed on examining and enhancing understanding of diabetes medications while addressing concerns among individuals of Chinese backgrounds to better understand the complexities of medication-taking behavior. Culturally relevant clinical discussion and structured diabetes education may support the development of health promoting medication beliefs potentially supporting optimal medication-taking behavior.

Despite increasing prevalence, early-onset type 2 diabetes (EOT2D) has received little clinical and qualitative research attention within England. This qualitative study aimed to explore and understand the unmet needs of people living with early-onset type 2 diabetes (PEOT2D) and their diabetes care within England.

Using semi-structured interviews, data was collected, transcribed and analysed from 25 PEOT2D and 25 healthcare professionals (HCPs). Taking an abductive approach, data for both cohorts were analysed and interpreted according to four constructs of Normalisation Process Theory (NPT): coherence (sense-making), cognitive participation (engagement), collective action (enactment) and reflexive monitoring (formal and informal appraisal).

Our findings revealed several unmet needs in current treatment and care for PEOT2D. The main unmet need was access to specialist care. Having GP (general practitioner) practices as their main caregivers presented a significant barrier to this population successfully carrying out their diabetes self-care. HCPs in specialist roles expressed similar views and were keen to see PEOT2D receive access to holistic and specialist care via a multidisciplinary team. Data interpretation according to the four constructs of NPT found that implementation of this approach would involve fostering an environment of support that allowed HCPs across the primary and secondary interface to do the following: (1) provide consultations incorporating person-centred care, shared decision-making, and non-judgemental and non-stigmatising behaviours and (2) work in an integrated and synchronous manner using streamlined referrals, interprofessional collaborations and team-based learning. Provision of tailored financial, human (additional staffing) and learning resources was found to be integral to allow creation of tailored multidisciplinary teams, and individual and collective skill enhancement of both specialist and primary care providers.

Although both PEOT2D and specialist care providers are keen for young adults with EOT2D to receive access to specialist and holistic care, there are several resource barriers that must be addressed to allow implementation of their desired approach to treatment and care. Further qualitative research with primary care providers (for example, GPs and practice nurses) involved in EOT2D care is needed to understand if (and how) their views and experiences differ from those providing specialist care.

To estimate the incidence and identify risk factors for diagnosed type 2 diabetes (T2D) among young U.S. adults.

We analyzed 142,884 adults aged 18-79 years with self-reported diabetes type from the cross-sectional National Health Interview Survey in 2016-2022, representing the noninstitutionalized U.S. civilian population. Incidence of diagnosed T2D was calculated for three age groups: young-adult onset (18-44 years), middle-age onset (45-64 years), and older-adult onset (65-79 years); the latter two groups were included to highlight the distinct risk factor profile of young-adult-onset T2D. Multivariable logistic regressions were used to identify risk factors for young-adult-onset T2D.

The estimated incidence of diagnosed young-adult-onset T2D was 3.0 per 1,000 adults (95% CI 2.6-3.5). Minority groups, socioeconomically disadvantaged individuals, and people with cardiometabolic diseases or psychological conditions had a higher incidence of diagnosed young-adult-onset T2D compared with their counterparts. Lipid-lowering medication use (adjusted odds ratio [aOR] 13.15, 95% CI 8.85-19.55), antihypertensive medication use (aOR 11.89, 95% CI 7.97-17.73), and obesity (BMI ≥30 vs. <25 kg/m2, aOR 10.89, 95% CI 6.69-17.7) were the strongest risk factors for young-adult-onset T2D; these risk factors, along with hypertension, hyperlipidemia, and coronary heart disease, were more strongly associated with young-adult-onset T2D compared with later-onset T2D, with up to 4.5 times higher aORs.

This study quantified the incidence of diagnosed young-adult-onset T2D in U.S. adults and identified its distinct risk factor profile. Targeted prevention strategies for young-adult-onset T2D are needed for minority and socioeconomically disadvantaged people and those with cardiometabolic diseases.

To examine the association between the age at onset of diabetes and the risk of all-cause mortality in a population of individuals diagnosed with type 2 diabetes mellitus (T2DM) and to identify risk factors associated with all-cause mortality in young-onset T2DM (YOD) patients in China.

This study utilized a cohort of 9759 patients who were diagnosed with T2DM and who were registered and enrolled in the National Basic Public Health Service Management Program in Qinghe District (now Qingjiangpu District) and Huai'an District, Huai'an City, Jiangsu Province, China. The patients were observed from November 2013 to July 2014, and all-cause mortality data were obtained by comprehensive matching with the Huai'an City Resident Mortality Database as of December 31, 2019. A Cox proportional hazards model was used to compute the hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) for all-cause mortality risk during the follow-up period among patients with varying disease onset ages. Additionally, subgroup analyses were conducted based on sex, age, lifestyle factors, and baseline clinical parameters.

A total of 7572 patients with T2DM, including 2874 men and 4698 women aged 57.9 ± 8.0 years, were ultimately included in the study. 1) At baseline, a greater proportion of YOD patients were engaged in high-intensity activities, had a longer sleep duration, had a longer duration of T2DM, had a family history of T2DM, had microvascular complications (kidney disease, retinopathy, neuropathy, diabetic foot, etc.), and received glucose-lowering treatment. Moreover, patients in the YOD group also had significantly greater baseline HbA1c, FBG, and estimated glomerular filtration rate (eGFR) than did those in the onset at 41-60 years (MD) group and the onset at 61-75 years (SD) group. 2) During the six-year follow-up period, a total of 1057 deaths were documented. After adjusting for confounding factors and utilizing SD as the reference group, the HRs for deaths occurring in the YOD and MD groups were 1.383 (95% CI: 0.717-2.667) and 1.006 (95% CI: 0.763-1.326), respectively. Moreover, the risk of death in the YOD group remained highest in the sensitivity analysis that excluded patients with coronary heart disease at baseline, stroke patients, and patients who died within the first three years of follow-up. 3) Sleep duration was identified as an independent risk factor for mortality in the YOD group, with a notable increase in the risk of all-cause mortality when sleep duration exceeded 9 hours per day.

The risk of all-cause mortality in YOD patients was 1.38 times greater than that in MD and SD patients, and the longer the sleep duration was, the greater the risk of death, especially when sleep duration exceeded 9 hours per day.

Youth-onset type 2 diabetes (T2D) results from genetic, environmental, and metabolic causes that differ among individuals and populations. This chapter builds on the 2022 ISPAD guidelines and summarizes recent advances in the management of T2D in children and adolescents. Updates include diagnostic algorithm for youth with new onset T2D, algorithms and tables for treatment, management, and assessment of comorbidities and complications and recommendations on recently approved pharmacologic therapies for the treatment of youth-onset T2D and management strategies. Youth-onset type 2 diabetes (T2D) results from genetic, environmental, and metabolic causes that differ among individuals and populations. This chapter builds on the 2022 ISPAD guidelines and summarizes recent advances in the management of T2D in children and adolescents. Updates include diagnostic algorithm for youth with new onset T2D, algorithms and tables for treatment, management, and assessment of comorbidities and complications and recommendations on recently approved pharmacologic therapies for the treatment of youth-onset T2D and management strategies.

Younger-onset type 2 diabetes is associated with accelerated complications. We assessed whether complications and mortality rates differed for younger age compared with older age at diagnosis over 30 years of follow-up.

In this study, we used data from the UKPDS, collected between 1977 and 2007, of participants aged 25-65 years with newly diagnosed type 2 diabetes with younger-onset (younger than 40 years) or later-onset (40 years or older), and without diabetes autoantibodies. We analysed standardised mortality ratios (SMR) using UK general population data, and incidence rates of prespecified outcomes by 10-year age intervals at diagnosis.

Of 4550 participants testing negative to all measured autoantibodies, 429 (9·4%) had younger-onset type 2 diabetes. 2704 (59·4%) were male, and mean HbA1c was 76 mmol/mol (SD 24·6). The median follow-up was 17·5 years (IQR 12·7-20·8). SMR for younger-onset type 2 diabetes was higher (3·72 [95% CI 2·98-4·64]) compared with later-onset type 2 diabetes (1·54 [1·47-1·61]). The incidence rate was higher for all outcomes in later-onset type 2 diabetes, except for microvascular disease (younger-onset 14·5 (11·9-17·7) vs later-onset 12·1 (11·3-13·0) per 1000 person-years). However, at any given age, the 5-year incidence of any diabetes-related endpoint, all-cause mortality, microvascular disease, and myocardial infarction was higher with younger age at diagnosis. Annual mean HbA1c was higher in the first 20 years in younger-onset compared with later-onset type 2 diabetes. Among participants randomised to intensive versus conventional glycaemic control, we observed no interactions by subgroup of younger-onset versus later-onset type 2 diabetes for any outcome.

The risk of dying relative to the general population is even greater for people diagnosed with type 2 diabetes at younger ages. The increased risk of complications and poorer glycaemic control in younger-onset type 2 diabetes calls for the development of services to identify and manage these individuals.

National Institute of Health and Care Research's Biomedical Research Centre.

To quantify rates of dementia treatment and death among Australians with type 2 diabetes relative to those without diabetes using linked national registries of Australia.

The study included 891,418 people with type 2 diabetes registered on the National Diabetes Services Scheme and a randomly sampled, population-based comparison group (n = 1,131,369). Outcomes included dementia death (all-cause dementia, Alzheimer's disease (AD) or vascular dementia), and first prescription of cholinesterase inhibitors or memantine.

Excess dementia risk was observed in the diabetes group for the composite outcome of all-cause dementia death or dementia medication prescription but varied with age at diabetes diagnosis and its duration. At age 70, the rate of dementia death/medication prescription was ∼1.3 (95% CI 1.2, 1.3) and 1.1 (95% CI 1.1, 1.2) times higher in people with ten and five years of diabetes duration, respectively. Individual outcomes showed that diabetes was associated with a higher incidence of vascular dementia death, whereas an increased risk of AD death was only observed beyond ∼10 years of diabetes duration. Further, the incidence of dementia medication prescription was lower among people with diabetes.

A higher incidence of AD death in the setting of 10+ years of diabetes duration coupled with a lower incidence of AD treatment suggests an under-recognition of this dementia phenotype among people with type 2 diabetes.

To investigate the relationship between age at diagnosis of type 2 diabetes and the risk of macrovascular disease, heart failure, and microvascular disease.

In August 2022, PubMed/EMBASE were searched for articles reporting (i) coronary artery disease, cerebrovascular disease, peripheral vascular disease, amputation; (ii) heart failure; and (iii) retinopathy, neuropathy, nephropathy (albuminuria, chronic kidney disease [CKD], end-stage renal disease) by age at diagnosis of type 2 diabetes. Random effects, non-linear dose-response meta-analysis was undertaken for each outcome to assess the association with age at diagnosis (40 years = reference), using both crude and maximally adjusted odds ratios separately, with and without adjustment for current age (age at sampling).

We identified 42 articles (230,003 to 3,465,590 participants; 1035 to 391,140 events). Age at diagnosis was positively associated with the risk of macrovascular diseases, heart failure, and CKD, independent of current age, and negatively associated with retinopathy. For other microvascular outcomes, when adjusting for current age, a "reverse U" relationship was observed (peak risk = 55-60 years).

Retinopathy was negatively associated with age at diagnosis, highlighting the importance of retinopathy screening in early-onset type 2 diabetes. The implications of other associations were unclear due to the heterogeneity in methodologies and findings.

The incidence and prevalence of type 2 diabetes mellitus (T2DM) in young individuals (aged <40 years) have significantly increased in recent years, approximating two to threefold increase in the respective rates. Numerous risk factors including severe obesity, family history, ethnicity, maternal diabetes or gestational diabetes, and female sex contribute to a younger age of onset. In terms of pathogenesis, impaired insulin secretion is the key operating mechanism, alongside with ectopic adiposity-related insulin resistance. T2DM diagnosis in a young adult requires the exclusion of type 1 diabetes mellitus (T1DM), latent autoimmune diabetes of adults (LADA) and maturity-onset diabetes of the young (MODY). The establishment of such diagnosis is critical for prognosis, because early-onset T2DM is associated with rapid deterioration in pancreatic β-cell secretory function leading to earlier initiation of insulin therapy. Furthermore, mortality and lifetime risk of developing complications, especially microvascular, is increased in these patients compared to both later-onset T2DM and T1DM patients; also, the latter are often developed earlier in the course of disease. The management of early-onset T2DM follows the same guidelines as in later-onset T2DM; yet patients aged 18-39 years are underrepresented in the big clinical trials on which the development of guidelines is based. Finally, young people with T2DM face significant challenges associated with social determinants, which compromise their adherence to therapy and induce diabetes distress. Future research focusing on the pathogenesis of β-cell decline and complications, as well as on specific treatment shall lead to better understanding and management of early-onset T2DM.

To examine the impact of current age, age at diagnosis, and duration of diabetes on the incidence rate of complications among people with type 2 diabetes.

Baseline data from 19,327 individuals with type 2 diabetes in the UK Biobank were analysed. Poisson regression was used to model incidence rates by current age, age at diagnosis, and duration of diabetes for the following outcomes: myocardial infarction (MI), heart failure (HF), stroke, end-stage kidney diseases (ESKD), chronic kidney diseases (CKD), liver diseases, depression, and anxiety.

The mean age at baseline was 60.2 years, and median follow-up was 13.9 years. Diabetes duration was significantly longer among those with younger-onset type 2 diabetes (diagnosed at <40 years) compared to later-onset type 2 diabetes (diagnosed at ≥40 years), 16.2 and 5.3 years, respectively. Incidence rates of MI, HF, stroke, and CKD had strong positive associations with age and duration of diabetes, whereas incidence rates of ESKD liver diseases, and anxiety mainly depended on duration of diabetes. The incidence rates of depression showed minor variation by age and duration of diabetes and were highest among those diagnosed at earlier ages. No clear evidence of an effect of age of onset of diabetes on risk of complications was apparent after accounting for current age and duration of diabetes.

Our study indicates age at diagnosis of diabetes does not significantly impact the incidence of complications, independently of the duration of diabetes. Instead, complications are primarily influenced by current age and diabetes duration.

Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow-up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shape life expectancy.

We evaluate prospectively these topics based on 270,075 eligible participants in the Nurses' Health Studies and Health Professionals Follow-up Study, leveraging repeated measurements throughout up to 40 years of follow-up. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

In fully adjusted analyses, incident early onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), and kidney disease (8.55, 1.98-36.9). The relative risk elevations declined dramatically with each higher decade of age at diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Longer disease duration was associated with generally higher relative and absolute risk of mortality.

Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy.

This review explores the emerging evidence regarding pathogenesis, future trajectories, treatment options, and phenotypes of youth-onset type 2 diabetes (T2D).

Youth-onset T2D is increasing in incidence and prevalence worldwide, disproportionately affecting First Nations communities, socioeconomically disadvantaged youth, and people of colour. Youth-onset T2D differs in pathogenesis to later-onset T2D and progresses more rapidly. It is associated with more complications, and these occur earlier. While there are limited licensed treatment options available, the available medications also appear to have a poorer response in youth with T2D. Multiple interacting factors likely contribute to this rising prevalence, as well as the increased severity of the condition, including structural inequities, increasing obesity and sedentary lifestyles, and intergenerational transmission from in-utero exposure to maternal hyperglycemia and obesity. Youth-onset T2D is also associated with stigma and poorer mental health, and these impact clinical management. There is an urgent need to develop effective interventions to prevent youth-onset T2D and enhance engagement of affected youth. It is also critical to better understand the differing phenotypes of youth-onset T2D, to effectively target treatments, and to address intergenerational transmission in high-risk populations.

Breast cancer is considered one of the most common neoplasms worldwide. Diabetes (DM) increases mortality among postmenopausal patients with breast cancer. Our study aims to identify the risk factors of DM-specific mortality and infiltrating ductal carcinoma (IDC) mortality in patients with IDC of the breast.

Data of IDC patients were obtained from the Surveillance, Epidemiology, and End Results database from 1975 to 2016. Independent variables included age, race, marital status, the primary site of IDC, breast subtype, the disease stage, grade, chemotherapy, radiation, and surgery. Kaplan-Meier, Cox and Binary regression tests were used to analyze the data using SPSS software.

A total of 673 533 IDC patients were analyzed. Of them, 4224 died due to DM and 116 822 died due to IDC. Factors that increase the risk of overall, IDC-specific, and DM-specific mortalities include older age, black race, widowed, uninsured, regional and distant stages, grade II and III, and no treatment with chemotherapy or radiotherapy or surgery. Additionally, the IDC mortality increased with separated status, all primary sites, all breast subtypes, and stage IV.

In patients with IDC, controlling DM besides cancer is recommended to reduce the mortality risk. Old, black, widowed, uninsured, regional and distant stages, grade II and III, and no treatment are common risk factors for DM- and IDC-mortality.

Over the past 20 years, the incidence and prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents have increased, particularly in racial and ethnic minorities. Despite the rise in T2DM in children and adolescents, the pathophysiology and progression of disease in this population are not clearly understood. Youth-onset T2DM has a more adverse clinical course than is seen in those who develop T2DM in adulthood or those with T1DM. Furthermore, the available therapeutic options are more limited for children and adolescents with T2DM compared to adult patients, mostly due to the challenges of implementing clinical trials. A better understanding of the mechanisms underlying the de-velopment and aggressive disease phenotype of T2DM in youth is important to finding effective prevention and management strategies. This review highlights the key evidence about T2DM in children and adolescents and its current burden and challenges both in clinical care and research activities.

The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) are increasing. The rise in frequency and severity of childhood obesity, inclination to sedentary lifestyle, and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes complications. Indeed, youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM, with greater insulin resistance and more rapid deterioration of beta cell function. Therefore, intermediate complications such as microalbuminuria develop in late childhood or early adulthood, while end-stage complications develop in mid-life. Due to the lack of efficacy and safety data, several drugs available for the treatment of adults with T2DM have not been approved in youth, reducing the pharmacological treatment options. In this mini review, we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.

This cross-sectional analysis of the Australian 3D study aimed to determine the prevalence of psychological distress and describe its associated characteristics in adults recently diagnosed with type 2 diabetes.

Adults (aged 18 years and over) who were recently diagnosed with type 2 diabetes (<6 months prior) were recruited through the Australian National Diabetes Services Scheme in 2018-2019. Demographic and health data were collected via interview-administered telephone surveys. Hierarchical regression was used to analyse whether demographic, self-care and clinical characteristics were associated with psychological distress, as measured by the K10 questionnaire.

Of the participants (n = 223), 26.3% presented with psychological distress, with 8.4% reporting mild, 8.4% reporting moderate and 9.5% reporting severe psychological distress. Neither age, sex, body mass index or taking anti-depressant medications were associated with the presence of psychological distress (p > .05). Being a smoker, living situation, less physical activity and poorer healthy eating beliefs and intentions were significantly associated with psychological distress in those not taking anti-depressant medications (p < .05). Being female was significantly associated with psychological distress in those taking anti-depressant medications (p < .05).

The study found that psychological distress is highly prevalent in adults recently diagnosed with type 2 diabetes. Behavioural factors such as smoking and low physical activity, as well as psycho-social factors such as living situation, poor healthy eating beliefs and intentions were significantly associated with psychological distress. This has implications for the management of people with newly diagnosed type 2 diabetes. SO WHAT?: Psychological distress is highly prevalent in Australian adults newly diagnosed with type 2 diabetes, emphasising the urgent need for enhanced psychological care to support this group.

The association of diabetes onset age and duration with incident arrhythmias remains unclear. This study evaluates the association of diabetes onset age and duration with incident arrhythmias and assesses modifications by the genetic predisposition to atrial fibrillation (AF).

We included 457,151 participants from the UK Biobank study. Multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) were used for the association between diabetes status, genetic predisposition, and risk of incident arrhythmias. The polygenic risk score (PRS) for AF comprised 142 single-nucleotide variants.

Over 12 years of follow-up, we documented 23,518 AF, 9079 bradyarrhythmia, 9280 conduction system diseases, 3358 supraventricular arrhythmias, and 3095 ventricular arrhythmias. Compared with non-diabetes, the risks of AF increased by 19%, 25%, and 36% for those with diabetes durations <5, 5-9, and ≥10 years, respectively. After multivariate adjustment, with the increase in diabetes onset age, the HRs of outcomes were gradually attenuated. The multivariable-adjusted HRs (95% CI) of diabetes for AF were 1.46 (1.24-1.71) in early middle age (<55 years), 1.21 (1.12-1.30) in late middle age (55-64 years), and 1.15 (1.06-1.24) in the elderly population (≥65 years). A significant interaction between diabetes status and AF-PRS for incident AF was observed (P for interaction <0.001). The same trends were observed for the other arrhythmias.

Diabetes was associated with higher risks of incident arrhythmias, and younger age at onset of diabetes was significantly associated with higher risk of subsequent arrhythmias.

Diabetes presenting at a younger age has a more aggressive nature. We aimed to explore the association of age at type 2 diabetes mellitus (T2DM) diagnosis with subsequent cancer incidence in a large Chinese population.

The prospective population-based longitudinal cohort included 428,568 newly diagnosed T2DM patients from 2011 to 2018. Participants were divided into six groups according to their age at diagnosis: 20-54, 55-59, 60-64, 65-69, 70-74, and ≥75 years. The incidence of overall and 14 site-specific cancers was compared with the Shanghai general population including 100,649,346 person-years.

A total of 18,853 and 582,643 overall cancer cases were recorded in the T2DM cohort and the general population. The age-standardized rate of overall cancer in T2DM patients was 501 (95% CI: 491, 511) per 100,000 person-years, and the standardized incidence ratio (SIR) was 1.10 (1.09, 1.12). Younger age at T2DM diagnosis was associated with higher incidence of overall and site-specific cancers. SIRs for overall cancer with T2DM diagnosis at ages 20-54, 55-59, 60-64, 65-69, 70-74, and ≥75 years were 1.48 (1.41, 1.54), 1.30 (1.25, 1.35), 1.19 (1.15, 1.23), 1.16 (1.12, 1.20), 1.06 (1.02, 1.10), and 0.86 (0.84, 0.89), respectively. Similar trends were observed for site-specific cancers, including respiratory, colorectum, stomach, liver, pancreatic, bladder, central nervous system, kidney, and gallbladder cancer and lymphoma among both males and females.

Our findings highlight the necessity of stratifying management for T2DM according to age of diagnosis. As with a range of vascular outcomes, age-standardized cancer risks are greater in earlier compared with later onset T2DM.

We aimed to investigate the association between the age at diagnosis of type 2 diabetes and the risk of cardiovascular (CVD) outcomes in comparison with nondiabetic counterparts.

A total of 634,350 patients with newly diagnosed type 2 diabetes between January 1, 2012, and December 31, 2014 were included in a Korean population cohort study. Nondiabetic matched controls were selected from the general population in a 1:2 ratio. Participants were followed until the end of 2019 for CVD outcomes and mortality.

During 5.7 years of follow-up, patients with type 2 diabetes diagnosed at ≤40 years of age had the highest excess risk for most outcomes relative to controls, with an adjusted hazard ratio (HR) (95 % CI) of 6.08 (5.51-6.70) for total mortality, 7.10 (6.66-7.58) for hospitalization for heart failure, and 5.04 (4.86-5.24) for coronary heart disease. All risks attenuated progressively with each increasing decade of diagnostic age.

In this population-based cohort study, a younger age at diagnosis of type 2 diabetes was associated with a higher relative risk of mortality and CVD outcomes. Therefore, primary prevention of type 2 diabetes is desirable at all ages but is particularly important at younger ages.

The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event.

Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/ ) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined.

The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log-alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure.

This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

We aimed to determine the impact of the duration of type 2 diabetes (T2D) on the risk of liver-related events and all-cause mortality in patients with NAFLD.

We conducted a territory-wide cohort study of adult patients with NAFLD diagnosed between January 1, 2000, and July 31, 2021, in Hong Kong. T2D was defined by the use of any antidiabetic agents, laboratory tests, and/or diagnosis codes. The primary endpoint was liver-related events, defined as a composite endpoint of HCC and cirrhotic complications. To conduct a more granular assessment of the duration of T2D, we employed landmark analysis in four different ages of interest (biological age of 40, 50, 60, and 70 years). By multivariable analysis with adjustment of non-liver-related deaths, compared with patients without diabetes at age 60 (incidence rate of liver-related events: 0.70 per 1,000 person-years), the adjusted subdistribution HR (SHR) of liver-related events was 2.51 (95% CI: 1.32-4.77; incidence rate: 2.26 per 1,000 person-years) in patients with T2D duration < 5 years, 3.16 (95% CI: 1.59-6.31; incidence rate: 2.54 per 1,000 person-years) in those with T2D duration of 6-10 years, and 6.20 (95% CI: 2.62-14.65; incidence rate: 4.17 per 1000 person-years) in those with T2D duration more than 10 years. A similar association between the duration of T2D and all-cause mortality was also observed.

Longer duration of T2D is significantly associated with a higher risk of liver-related events and all-cause mortality in patients with NAFLD.

Concurrent insulin resistance and elevated blood pressure are commonly observed in cardiovascular disease (CVD) and have long been proposed to contribute to CVD. However, the temporal relationship between them and the effect of their cumulative co-exposure on future incident CVD remains unclear.

Longitudinal analysis of data on 57,192 participants from a real-world, prospective cohort study (Kailuan Study) was performed to address the temporal relationship between Triglyceride-Glucose Index (TyG, calculated as ln [TG (mg/dL) × FBG (mg/dL)/2]) and blood pressure (BP) assessed by cross-lagged analyses in an approximately 4-year exposure period (2006/2007 to 2010/2011). After excluding 879 participants with known diabetes, 56,313 nonCVD participants were included for further analysis of the CVD outcome. Cox regression models were used to examine the hazard ratios (HRs) upon the cumulative TyG (CumTyG) and BP(CumBP) in the exposure period.

The standard regression coefficient from baseline TyG to follow-up systolic BP was 0.0142 (95% CI 0.0059-0.0226), which was greater than the standard regression coefficient from baseline systolic BP to follow-up TyG (- 0.0390; 95% CI - 0.0469 to - 0.0311). The same results were observed in the cross-lag between TyG and diastolic blood pressure [0.0271 (0.0185 to 0.0356) vs. - 0.0372 (- 0.0451 to - 0.0293)]. During a median follow-up of 9.98 years, 3981 CVD cases occurred. Significant interactions were observed between the median CumTyG (8.61) and CumSBP thresholds (130, 140 mmHg) (P = 0.0149), the median CumTyG (8.61) and CumDBP thresholds (80, 90 mmHg) (P = 0.0441). Compared to CumTyG < 8.61 and CumSBP < 130 mmHg, after adjusting for potential confounding factors, the HR gradually increased in the high co-exposure groups. The hazard ratios (HRs) and 95% confidence intervals (CIs) for Q2-Q6 were 1.39 (1.24, 1.57), 1.94 (1.69, 2.22), 2.40 (2.12, 2.71), 2.74 (2.43, 3.10), and 3.07 (2.74, 3.45). Additionally, the CVD risks in the co-exposure were more prominent in younger participants.

These findings suggest that elevated TyG has a greater impact on future blood pressure changes than vice versa. Dual assessment and management of insulin resistance and blood pressure contribute to the prevention of CVD, especially in younger individuals.

The Triglyceride-glucose (TyG) index, a novel indicator of insulin resistance, has been associated with mortality from coronary artery diseases, ischemic stroke, and heart failure. In recent years, much emphasis has been placed on the relationship between the TyG index and mortality in the general population. However, the impact of age on the association between TyG and all-cause and cardiovascular mortality remains controversial. This study investigated the link between the TyG index and all-cause and cardiovascular mortality, emphasizing differences between older and non-older populations.

Data from the National Health and Nutrition Examination Survey (2009-2018), encompassing 20,194 participants, were analyzed. The baseline TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate Cox proportional hazards regression models with restricted cubic splines and trend tests were employed to explore the association between the TyG index and all-cause and cardiovascular mortality, with emphasis on age-specific analysis. Subgroup analysis was conducted to examine whether the TyG index's association with mortality varied across different subgroups. Additionally, receiver operating characteristic curves were used to compare the predictive ability of the TyG index with the homeostasis model assessment of insulin resistance (HOMA-IR) for all-cause and cardiovascular mortality.

Over a median follow-up period of 105 months, all-cause mortality accounted for 13.345% of cases, and cardiovascular mortality accounted for 3.387%. Kaplan-Meier curves showed a significant increase in all-cause and cardiovascular mortality with higher TyG index values (both P for log-rank test < 0.001). However, during Cox proportional hazards regression analysis, no linear trend was observed between the TyG index and all-cause or cardiovascular mortality after adjusting for confounding factors (all-cause mortality: P for trend = 0.424; cardiovascular mortality: P for trend = 0.481). Restricted cubic splines revealed a non-linear association between the baseline TyG index and all-cause and cardiovascular mortality in the overall population (all-cause mortality: Non-linear P = 0.003; cardiovascular mortality: Non-linear P = 0.034). The effect of the TyG index was consistent across most subgroups in terms of all-cause and cardiovascular mortality, with no significant interaction with randomized factors (all-cause mortality: P for interaction = 0.077-0.940, cardiovascular mortality: P for interaction = 0.173-0.987), except for the age subgroup (all-cause mortality: P for interaction < 0.001, cardiovascular mortality: P for interaction < 0.001). Further age-specific analysis revealed that the association between the TyG index and all-cause and cardiovascular mortality remained significant in patients aged < 65 but not in those aged ≥ 65. Interestingly, a non-linear association was observed between the TyG index and all-cause mortality in individuals aged < 65 (Non-linear P = 0.011), while a linear relationship was observed with cardiovascular mortality, showing an upward trend (Non-linear P = 0.742, P for trend = 0.010). Further stratification according to age yielded similar results only in patients aged 45-64 (all-cause mortality: Non-linear P = 0.001 and cardiovascular mortality: Non-linear P = 0.902, P for trend = 0.015). Compared to HOMA-IR, the TyG index demonstrated superior predictive performance for all-cause and cardiovascular mortality (all-cause mortality: 0.620 vs. 0.524, P < 0.001; cardiovascular mortality: 0.623 vs. 0.537, P < 0.001).

This study established a significant association between the TyG index and all-cause and cardiovascular mortality in the general population, particularly among individuals aged < 65. Notably, a non-linear association with all-cause mortality was observed in those aged < 65, while a linear relationship with cardiovascular mortality was found.

To examine the associations between age at type 2 diabetes diagnosis and the relative and absolute risk of all-cause and cause-specific mortality in England.

In this cohort study using primary care data from the Clinical Practice Research Datalink, we identified 108,061 individuals with newly diagnosed type 2 diabetes (16-50 years of age), matched to 829,946 individuals without type 2 diabetes. We estimated all-cause and cause-specific mortality (cancer, cardiorenal, other [noncancer or cardiorenal]) by age at diagnosis, using competing-risk survival analyses adjusted for key confounders.

Comparing individuals with versus without type 2 diabetes, the relative risk of death decreased with an older age at diagnosis: the hazard ratio for all-cause mortality was 4.32 (95% CI 3.35-5.58) in individuals diagnosed at ages 16-27 years compared with 1.53 (95% CI 1.46-1.60) at ages 48-50 years. Smaller relative risks by increasing age at diagnosis were also observed for cancer, cardiorenal, and noncancer or cardiorenal death. Irrespective of age at diagnosis, the 10-year absolute risk of all-cause and cause-specific mortality were higher in individuals with type 2 diabetes; yet, the absolute differences were small.

Although the relative risk of death in individuals with versus without type 2 was higher at younger ages, the 10-year absolute risk of all investigated causes of death was small and similar in the two groups. Further multidecade studies could help estimate the long-term risk of complications and death in individuals with early-onset type 2 diabetes.

To investigate the association between duration of type 2 diabetes and cancer incidence.

In the Clinical Practice Research Datalink database, we identified 130,764 individuals with type 2 diabetes aged ≥35 years at diagnosis who were linked to hospital and mortality records. We used sex-stratified Royston-Parmar models with two timescales to estimate incidence rates of all cancers, the four commonest cancers in the U.K. (colorectal, lung, prostate, breast), and the obesity-related cancers (e.g., liver, ovary) between 1 January 1998 and 14 January 2019, by age and diabetes duration.

During 1,089,923 person-years, 18,977 incident cancers occurred. At the same age, rates of all cancers in men and women did not vary across durations ranging from diagnosis to 20 years; conversely, for any duration, there was a strong, positive association between age and cancer rates. In men, the rate ratio (95% CI) comparing 20 with 5 years of duration was 1.18 (0.82-1.69) at 60 years of age and 0.90 (0.75-1.08) at 80 years; corresponding ratios in women were 1.07 (0.71-1.63) and 0.84 (0.66-1.05). This pattern was observed also for the four commonest cancers. For obesity-related cancers, although rates were generally higher in individuals with a higher BMI, there was no association with duration at any level of BMI.

In this study, we did not find evidence of an association between duration of type 2 diabetes and risk of cancer, with the higher risk observed for longer durations related to ageing.

Different ages for diagnosis of diabetes have diverse effects on risks of cardiovascular disease, dementia, and mortality, but there is little evidence of cancer. This study investigated the relationship between diabetes at different diagnostic ages and risks of cancer incidence and mortality in people aged 37-73 years.

Participants with diabetes in the UK Biobank prospective cohort were divided into four groups: ≤40, 41-50, 51-60, and >60 years according to age at diagnosis. A total of 26,318 diabetics and 105,272 controls (1:4 randomly selected for each diabetic matched by the same baseline age) were included. We calculated the incidence density, standardized incidence, and mortality rates of cancer. Cox proportional hazard model was used to examine the associations of diabetes at different diagnostic ages with cancer incidence and mortality, followed by subgroup analyses.

Compared to corresponding controls, standardized incidence and mortality rates of overall and digestive system cancers were higher in diabetes diagnosed at age 41-50, 51-60, and >60 years, especially at 51-60 years. Individuals diagnosed with diabetes at different ages were at higher risk to develop site-specific cancers, with a prominently increased risk of liver cancer since the diagnosis age of >40 years. Significantly, participants with diabetes diagnosed at 51-60 years were correlated with various site-specific cancer risks [hazard ratio (HR) for incidence: 1.088-2.416, HR for mortality: 1.276-3.269]. Moreover, for mortality of digestive system cancers, we observed an interaction effect between smoking and diabetes diagnosed at 51-60 years.

Our findings highlighted that the age at diagnosis of diabetes, especially 51-60 years, was critical risks of cancer incidence and mortality and may represent a potential preventative window for cancer.

The prevalence of type 2 diabetes is increasing rapidly, particularly among younger age groups. Estimates suggest that people with diabetes die, on average, 6 years earlier than people without diabetes. We aimed to provide reliable estimates of the associations between age at diagnosis of diabetes and all-cause mortality, cause-specific mortality, and reductions in life expectancy.

For this observational study, we conducted a combined analysis of individual-participant data from 19 high-income countries using two large-scale data sources: the Emerging Risk Factors Collaboration (96 cohorts, median baseline years 1961-2007, median latest follow-up years 1980-2013) and the UK Biobank (median baseline year 2006, median latest follow-up year 2020). We calculated age-adjusted and sex-adjusted hazard ratios (HRs) for all-cause mortality according to age at diagnosis of diabetes using data from 1 515 718 participants, in whom deaths were recorded during 23·1 million person-years of follow-up. We estimated cumulative survival by applying age-specific HRs to age-specific death rates from 2015 for the USA and the EU.

For participants with diabetes, we observed a linear dose-response association between earlier age at diagnosis and higher risk of all-cause mortality compared with participants without diabetes. HRs were 2·69 (95% CI 2·43-2·97) when diagnosed at 30-39 years, 2·26 (2·08-2·45) at 40-49 years, 1·84 (1·72-1·97) at 50-59 years, 1·57 (1·47-1·67) at 60-69 years, and 1·39 (1·29-1·51) at 70 years and older. HRs per decade of earlier diagnosis were similar for men and women. Using death rates from the USA, a 50-year-old individual with diabetes died on average 14 years earlier when diagnosed aged 30 years, 10 years earlier when diagnosed aged 40 years, or 6 years earlier when diagnosed aged 50 years than an individual without diabetes. Using EU death rates, the corresponding estimates were 13, 9, or 5 years earlier.

Every decade of earlier diagnosis of diabetes was associated with about 3-4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes.

British Heart Foundation, Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.

Non-targeted metabonomic techniques were used to explore changes in metabolic profiles of patients with early onset and late onset T2DM. Newly diagnosed early onset T2DM (EarT2DM) and late onset T2DM (LatT2DM) patients were recruited, and the matched age, sex, and low-risk population of diabetes mellitus were selected as the control group. 117 adults were recruited in the study, including 21 in EarT2DM group with 25 in corresponding control group (heaCG1), and 48 in LatT2DM group with 23 in corresponding control group (heaCG2). There were 15 relatively distinctive metabolic variants in EarT2DM group and 10 distinctive metabolic variants in LatT2DM group. The same changing pathways mainly involved protein, aminoacyl-tRNA biosynthesis, fatty acid biosynthesis, taurine metabolism, arginine biosynthesis, lysosome and mTOR signaling pathway. The independent disturbed pathways in EarT2DM included branched chain amino acids, alanine, aspartate and glutamate metabolism. The independent disturbed pathways in LatT2DM involved linoleic acid metabolism, biosynthesis of unsaturated fatty acids, arginine, proline metabolism and FoxO signaling pathway. T2DM patients at different diagnosed ages may have different metabolite profiles. These metabolic differences need to be further verified.

Diabetes affects the structure of the blood vessel walls. Since the blood vessel walls are made of birefringent organized tissue, any change or damage to this organization can be evaluated using polarization-sensitive optical coherence tomography (PS-OCT). In this paper, we used PS-OCT along with the blood vessel wall birefringence index (BBI = thickness/birefringence2) to non-invasively assess the structural integrity of the human retinal blood vessel walls in patients with diabetes and compared the results to those of healthy subjects. PS-OCT measurements revealed that blood vessel walls of diabetic patients exhibit a much higher birefringence while having the same wall thickness and therefore lower BBI values. Applying BBI to diagnose diabetes demonstrated high accuracy (93%), sensitivity (93%) and specificity (93%). PS-OCT measurements can quantify small changes in the polarization properties of retinal vessel walls associated with diabetes, which provides researchers with a new imaging tool to determine the effects of exercise, medication, and alternative diets on the development of diabetes.

We investigated the risk of developing chronic kidney disease (CKD) in patients with young-onset Type 2 diabetes (YOD, diagnosed age < 40 years). We enrolled 84,384 patients aged 20-64 who started anti-diabetic medication between 2010 and 2011 from the Korea National Health Insurance Sharing Service; patients with Type 1 diabetes or a history of CKD were excluded. Multivariate logistic regression analyses were performed to adjust for YOD-distinct variables and compare the incidence of CKD between YOD and late-onset diabetes (LOD, diagnosed age ≥ 40 years). During the median observation period of 5.16 years (interquartile range: 4.58-5.77 years), 1480 out of 77,039 LOD patients and 34 out of 7345 YOD patients developed CKD. Patients with YOD had distinct baseline characteristics compared with the patients with LOD. The odds ratio of developing CKD in patients with YOD over LOD was 1.70 (95% CI 1.15-2.51) after adjusting clinically distinct variables. The increased CKD odds in YOD compared with LOD was greater in the non-smoking group (OR 2.03, 95% CI 1.26-3.26) than in the smoking group (OR 1.49, 95% CI 0.74-2.98, p = 0.0393 for interaction). Among YOD patients, hypertension (34.76% vs. 64.71%, p = 0.0003), dyslipidemia (46.87% vs. 73.53%, p = 0.0019), and sulfonylurea use (35.54% vs. 52.94%, p = 0.0345) were associated with CKD development. YOD patients have a greater risk of developing CKD than LOD patients after adjusting clinically distinct variables.

The association of incident cardiometabolic multimorbidity (CMM) with mortality risk is rarely studied, and neither are the durations of cardiometabolic diseases (CMDs). Whether the association patterns of CMD durations with mortality change as individuals progress from one CMD to CMM is unclear.

Data from China Kadoorie Biobank of 512,720 participants aged 30-79 was used. CMM was defined as the simultaneous presence of two or more CMDs of interest, including diabetes, ischemic heart disease, and stroke. Cox regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the duration-dependent associations of CMDs and CMM with all-cause and cause-specific mortality. All information on exposures of interest was updated during follow-up.

During a median follow-up of 12.1 years, 99,770 participants experienced at least one incident CMD, and 56,549 deaths were documented. Among 463,178 participants free of three CMDs at baseline, compared with no CMD during follow-up, the adjusted HRs (95% CIs) between CMM and all-cause mortality, mortality from circulatory system diseases, respiratory system diseases, cancer, and other causes were 2.93 (2.80-3.07), 5.05 (4.74-5.37), 2.72 (2.35-3.14), 1.30 (1.16-1.45), and 2.30 (2.02-2.61), respectively. All CMDs exhibited a high mortality risk in the first year of diagnosis. Subsequently, with prolonged disease duration, mortality risk increased for diabetes, decreased for IHD, and sustained at a high level for stroke. With the presence of CMM, the above association estimates inflated, but the pattern of which remained.

Among Chinese adults, mortality risk increased with the number of the CMDs and changed with prolonged disease duration, the patterns of which varied among the three CMDs.

We propose a semiparametric mean residual life mixture cure model for right-censored survival data with a cured fraction. The model employs the proportional mean residual life model to describe the effects of covariates on the mean residual time of uncured subjects and the logistic regression model to describe the effects of covariates on the cure rate. We develop estimating equations to estimate the proposed cure model for the right-censored data with and without length-biased sampling, the latter is often found in prevalent cohort studies. In particular, we propose two estimating equations to estimate the effects of covariates in the cure rate and a method to combine them to improve the estimation efficiency. The consistency and asymptotic normality of the proposed estimates are established. The finite sample performance of the estimates is confirmed with simulations. The proposed estimation methods are applied to a clinical trial study on melanoma and a prevalent cohort study on early-onset type 2 diabetes mellitus.

The burden of type 2 diabetes (T2D) differs between socioeconomic groups. The present study combines ongoing and plausible trends in T2D incidence and survival by income to forecast future trends in cases of T2D and life expectancy with and without T2D up to year 2040. Using Finnish total population data for those aged 30 years on T2D medication and mortality in 1995-2018, we developed and validated a multi-state life table model using age-, gender-, income- and calendar year-specific transition probabilities. We present scenarios based on constant and declining T2D incidence and on the effect of increasing and decreasing obesity on T2D incidence and mortality states up to 2040. With constant T2D incidence at 2019-level, the number of people living with T2D would increase by about 26% between 2020 and 2040. The lowest income group could expect more rapid increases in the number with T2D compared to the highest income group (30% vs. 23% respectively). If the incidence of T2D continues the recent declining trend, we predict about 14% fewer cases. However, if obesity increases two-fold, we predict 15% additional T2D cases. Unless, we reduce the obesity-related excess risk, the number of years lived without T2D could decrease up to 6 years for men in the lowest income group. Under all plausible scenarios, the burden of T2D is set to increase and it will be unequally distributed among socioeconomic groups. An increasing proportion of life expectancy will be spent with T2D.

Few studies have examined the relationship between malnutrition, as defined by the Geriatric Nutrition Risk Index (GNRI), and all-cause mortality and cardiovascular mortality events, particularly in persons with diabetes. The study aimed at the association between GNRI and all-cause mortality and cardiovascular mortality in older Americans with diabetes.

Data from this retrospective study were obtained from the National Health and Nutrition Examination (NHANES) 1999-2016. Using data from The NHANES Public-Use Linked Mortality Files to assess all-cause mortality (ACM) and cardiovascular mortality (CVM). After excluding participants younger than 60 years and without diabetes, and with missing follow-up data, 4400 cases were left in this study. Persons with diabetes were divided by GNRI into 3 groups: GNRI ≥ 98; 92 ≤ GNRI < 98; and GNRI < 92; (No; Low; Moderate/Severe (M/S) group). We used Cox proportional hazard regression model to explore the predictive role of GNRI on ACM and CVM in elderly persons with diabetes. Restricted cubic splines to investigate the existence of a dose-response linear relationship between them.

During a median follow-up period of 89 months, a total of 538 (12.23%) cardiovascular deaths occurred and 1890 (42.95%) all-cause deaths occurred. Multifactorial COX regression analysis showed all-cause mortality (hazard ratio [HR]: 2.58, 95% CI: 1.672-3.994, p < 0.001) and cardiovascular mortality (HR: 2.29, 95% CI: 1.063-4.936, p = 0.034) associated with M/S group risk of malnutrition in GNRI compared to no group. A negative association between GNRI and all-cause mortality was observed across gender and ethnicity. However, the same negative association between GNRI and cardiovascular mortality was observed only for males (HR:0.94, 95% CI:0.905-0.974, p < 0.001) and other races (HR:0.92, 95% CI:0.861-0.976, p = 0.007). And there was no significant correlation between low malnutrition and cardiovascular mortality (p = 0.076). Restricted cubic splines showed a nonlinear relationship between GNRI and all-cause mortality and cardiovascular mortality (non-linear p < 0.001, non-linear p = 0.019).

Lower GNRI levels are associated with mortality in older patients with diabetes. GNRI may be a predictor of all-cause mortality and cardiovascular mortality risk in older patients with diabetes.

Diabetes mellitus (DM) is a comorbidity commonly presenting with metabolic-dysfunction-associated fatty liver disease (MAFLD); however, few tests for interaction have been reported. Our target was to evaluate the prognostic implications of DM in patients with different forms of MAFLD.

Using data from the Third National Health and Nutrition Examination Survey (NHANES III) in the United States, we screened 14,797 participants aged 20-74 who received ultrasound examinations from 1988-1994. Among them, 4599 patients met the diagnosis of MAFLD, and we defined mortality as the outcome event. Survival analysis of competitive risk events was performed using Cox regression and sub-distributed risk ratio (SHR).

During 21.1 years of follow-up, cardiovascular diseases seemed to be the most common cause of death among MAFLD patients. Of them, DM was present in 25.48% and was independently associated with increased risk of all-cause mortality (HRs: 1.427, 95% CIs: 1.256-1.621, p < 0.001) and cause-specific mortality (cardiovascular-related mortality (HRs: 1.458, 95% CIs: 1.117-1.902, p = 0.005), non-cardiovascular-related mortality (HRs: 1.423, 95% CIs: 1.229-1.647, p < 0.001), and non-cancer-related mortality (HRs: 1.584, 95% CIs: 1.368-1.835, p < 0.001), respectively). Surprisingly, this association was more significant for young patients (p-value for interaction <0.001). Moreover, DM had a greater risk of all-cause and cause-specific mortality among overweight and obese MAFLD patients (p-value for interaction <0.001).

DM increased the risk of all-cause and cause-specific mortality (cardiovascular-related, non-cardiovascular-related, and non-cancer-related) in MAFLD patients, especially in younger patients with excess obesity.

The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) and its complications are increasing worldwide. Youth-onset T2DM has been reported in all racial and ethnic groups, but Indigenous peoples and people of colour are disproportionately affected. People with youth-onset T2DM often have a more aggressive clinical course than those with adult-onset T2DM or those with type 1 diabetes mellitus. Moreover, the available treatment options for children and adolescents with T2DM are more limited than for adult patients. Intermediate complications of youth-onset T2DM, such as increased albuminuria, often develop in late childhood or early adulthood, and end-stage complications, including kidney failure, develop in mid-life. The increasing frequency, earlier onset and greater severity of childhood obesity in the past 50 years together with increasingly sedentary lifestyles and an increasing frequency of intrauterine exposure to diabetes are important drivers of the epidemic of youth-onset T2DM. The particularly high risk of the disease in historically disadvantaged populations suggests an important contribution of social and environmental factors, including limited access to high-quality health care, healthy food choices and opportunities for physical activity as well as exposure to stressors including systemic racism and environmental pollutants. Understanding the mechanisms that underlie the development and aggressive clinical course of youth-onset T2DM is key to identifying successful prevention and management strategies.