Incident Type 2 Diabetes Research Articles

Measurement of cumulative high-sensitivity C-reactive protein and monocyte to high-density lipoprotein ratio in the risk prediction of type 2 diabetes: a prospective cohort study

BackgroundConverging data have suggested that monocytic inflammation and C-reactive protein (CRP) are biologically intertwined processes and are involved in diabetogenesis. This study aimed to investigate the association between systemic inflammation assessed by joint cumulative high-sensitivity C-reactive protein (CumCRP) and monocyte to high-density lipoprotein ratio (CumMHR) and incident type 2 diabetes (T2D) and their predictive value for T2D in a general population.MethodsA total of 40,813 nondiabetic participants from a prospective real-life cohort (Kailuan Study, China) were followed biennially from 2010/2011 until December 31, 2020. Multivariable Cox regression analyses were conducted to evaluate the adjusted hazard ratios (aHRs) of incident diabetes.ResultsDuring a median follow-up of 7.98 (IQR: 5.74–8.87) years, 4848 T2D cases developed. CumMHR and CumCRP were alone or jointly associated with incident T2D after adjusting for potential confounders. Elevated CumMHR levels significantly increased the risk of incident diabetes in each CumCRP strata (P-interaction: 0.0278). Participants with concomitant elevations in CumMHR and CumCRP levels had the highest risk (aHR: 1.71, 95% CI 1.52–1.91) compared to both in the low strata. Notably, the coexposure-associated T2D risk was modified by age, sex, hypertension, dyslipidemia, and prediabetes status. C-statistics increased from 0.7377 to 0.7417 when CumMHR and CumCRP were added into the multivariable-adjusted model, with a net reclassification improvement (%) of 12.39 (9.39–15.37) (P < 0.0001).ConclusionsCumulative hsCRP and MHR were both independently and jointly associated with an increased risk of T2D and their addition to established risk factors should improve risk prediction and reclassification of diabetes.

Adipose tissue-derived metabolite risk scores and risk for type 2 diabetes in South Asians

BackgroundSouth Asians are at higher risk for type 2 diabetes (T2D) than many other race/ethnic groups. Ectopic adiposity, specifically hepatic steatosis and visceral fat may partially explain this. Our objective was to derive metabolite risk scores for ectopic adiposity and assess associations with incident T2D in South Asians.MethodsWe examined 550 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort study aged 40–84 years without known cardiovascular disease or T2D and with metabolomic data. Computed tomography scans at baseline assessed hepatic attenuation and visceral fat area, and fasting serum specimens at baseline and after 5 years assessed T2D. LC-MS-based untargeted metabolomic analysis was performed followed by targeted integration and reporting of known signals. Elastic net regularized linear regression analyses was used to derive risk scores for hepatic steatosis and visceral fat using weighted coefficients. Logistic regression models associated metabolite risk score and incident T2D, adjusting for age, gender, study site, BMI, physical activity, diet quality, energy intake and use of cholesterol-lowering medication.ResultsAverage age of participants was 55 years, 36% women with an average body mass index (BMI) of 25 kg/m2 and 6% prevalence of hepatic steatosis, with 47 cases of incident T2D at 5 years. There were 445 metabolites of known identity. Of these, 313 metabolites were included in the MET-Visc score and 267 in the MET-Liver score. In most fully adjusted models, MET-Liver (OR 2.04 [95% CI 1.38, 3.03]) and MET-Visc (OR 2.80 [1.75, 4.46]) were associated with higher odds of T2D. These associations remained significant after adjustment for measured adiposity.ConclusionsMetabolite risk scores for intrahepatic fat and visceral fat were strongly related to incident T2D independent of measured adiposity. Use of these biomarkers to target risk stratification may help capture pre-clinical metabolic abnormalities.

Plasma metabolite profile of legume consumption and future risk of type 2 diabetes and cardiovascular disease

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 different known metabolites and legume consumption were performed using elastic net regression. Associations between the identified metabolite profile and incident T2D and CVD were estimated using multivariable Cox regression models.ResultsSpecific metabolic signatures of legume consumption were identified, these included amino acids, cortisol, and various classes of lipid metabolites including diacylglycerols, triacylglycerols, plasmalogens, sphingomyelins and other metabolites. Among these identified metabolites, 22 were negatively and 18 were positively associated with legume consumption. After adjustment for recognized risk factors and legume consumption, the identified legume metabolite profile was inversely associated with T2D incidence (hazard ratio (HR) per 1 SD: 0.75, 95% CI 0.61–0.94; p = 0.017), but not with CVD incidence risk (1.01, 95% CI 0.86–1.19; p = 0.817) over the follow-up period.ConclusionsThis study identified a set of 40 metabolites associated with legume consumption and with a reduced risk of T2D development in a Mediterranean population at high risk of cardiovascular disease.Trial registration: ISRCTN35739639.

Hemoglobin A1c and Type 2 Diabetes Incidence Among Adolescents With Overweight and Obesity.

With the increase in prediabetes among adolescents with overweight and obesity, identifying those at highest risk for type 2 diabetes (T2D) can support prevention strategies. To assess T2D risk by hemoglobin A1c (HbA1c) levels among adolescents with overweight and obesity. This retrospective cohort study was conducted using data for January 1, 2010, to December 31, 2019, from a large California health care system. The study population comprised adolescents aged 10 to 17 years who had a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) at or above the 85th percentile, had HbA1c measured during 2010 to 2018, and did not have preexisting diabetes. Data abstraction and analyses were conducted from January 1, 2020, to November 16, 2023. Baseline HbA1c, with covariates including BMI category (overweight: 85th to <95th percentile; moderate obesity: 100% to <120% of 95th percentile; or severe obesity: ≥120% of 95th percentile), age, sex, race and ethnicity, and Neighborhood Deprivation Index score. The main outcome was incident T2D during follow-up through 2019, including cumulative incidence and multivariable hazard ratios (HRs) with 95% CIs using Cox proportional hazard regression analyses. This study included 74 552 adolescents with a mean (SD) age of 13.4 (2.3) years. More than half (50.6%) were female; 26.9% of individuals had overweight, 42.3% had moderate obesity, and 30.8% had severe obesity. Individuals identified as Asian or Pacific Islander (17.6%), Black (11.1%), Hispanic (43.6%), White (21.6%), and other or unknown race or ethnicity (6.1%). During follow-up, 698 adolescents (0.9%) developed diabetes, and 626 (89.7%) had T2D; 72 individuals (10.3%) who had type 1, secondary, or other diabetes were censored. The overall T2D incidence was 2.1 (95% CI, 1.9-2.3) per 1000 person-years, with a 5-year cumulative incidence of 1.0% (95% CI, 0.9%-1.1%). Higher baseline HbA1c (from <5.5% to 5.5%-5.6%, 5.7%-5.8%, 5.9%-6.0%, 6.1%-6.2%, and 6.3-6.4%) was associated with higher 5-year cumulative T2D incidence (from 0.3% [95% CI, 0.2%-0.4%] to 0.5% [0.4%-0.7%], 1.1% [0.8%-1.3%], 3.8% [3.2%-4.7%], 11.0% [8.9%-13.7%], and 28.5% [21.9%-36.5%], respectively). In addition, higher baseline HbA1c was associated with greater T2D risk (reference [HbA1c <5.5%]: HR, 1.7 [95% CI, 1.3-2.2], 2.8 [2.1-3.6], 9.3 [7.2-12.1], 23.3 [17.4-31.3], and 71.9 [51.1-101.1], respectively). Higher BMI category, older age, female sex, and Asian or Pacific Islander race (HR, 1.7 [95% CI, 1.3-2.2]), but not Black race or Hispanic ethnicity (compared with White race), were also independent indicators of T2D. In stratified analyses, incremental risk associated with higher HbA1c was greater for Asian or Pacific Islander and White adolescents than for Black and Hispanic adolescents. In this cohort study of adolescents with overweight and obesity, T2D risk increased substantially with baseline HbA1c above 6.0%. Risk varied by BMI, age, sex, and race and ethnicity. These findings suggest that diabetes surveillance in adolescents should be tailored to optimize identification among high-risk subgroups.

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

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). 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 regression models adjusting for body mass index at the blood draw, and other established T2D risk factors. The percentage of women progressing to T2D ranged from 10% in the bottom T2D metabolomics score quartile to 78% in the highest score quartile. Adjusting for established T2D risk factors, women in the highest quartile had more than a 20-fold greater diabetes risk than women in the lowest quartile (odds ratios [OR]=23.1 [95% CI=8.6, 62.1]; p for trend<0.001). The continuous T2D metabolomics score was strongly and positively associated with incident T2D (adjusted OR=2.7 per SD [95% CI=1.9, 3.7], p<0.0001). A pattern of plasma metabolites among high-risk women is associated with a markedly elevated risk of progression to T2D later in life.

Cumulative ADHD medication use and risk of type 2 diabetes in adults: a Swedish Register study

BackgroundLittle is known about the impact of cumulative attention-deficit/hyperactivity disorder (ADHD) medication use on the risk of type 2 diabetes (T2D).ObjectiveThe objective is to examine the association between cumulative use...

Determinants of adult sedentary behavior and physical inactivity for the primary prevention of diabetes in historically disadvantaged communities: A representative cross-sectional population-based study from Reunion Island.

Populations undergoing extensive and rapid socio-economic transitions including historically disadvantaged communities face an increased risk of type-2 diabetes (T2D). In recent years, sedentary behavior and physical inactivity have been considered modifiable determinants when developing primary prevention programs to reduce T2D incidence. Reunion Island is a French overseas department with an increasing T2D population and a high level of socio-economic inequality. The objectives of our study were to identify the individual, social, and environmental factors associated with sedentary behavior and physical inactivity among the Reunion Island adult population, and to highlight these findings in order to propose T2D primary prevention strategies aiming at alleviating local social inequalities in health (SIH). In 2021, we conducted a population-based cross-sectional telephone survey using random sampling. Participants included adults over 15 years old living in ordinary accommodation on Reunion Island (n = 2,010). Using a sequential approach, multinomial logistic regression model (explaining 3 profiles of interest: sedentary/inactive, sedentary/active, non-sedentary/inactive), and sampling-design weighted estimates, we found that 53.9% [95% confidence interval: 51.1 to 56.7%] of participants had sedentary behavior and 20.1% [95% CI: 17.8 to 22.5%] were inactive. Abandoning physical activity due to the COVID-19 pandemic (p<0.001), final secondary school diploma or above (p = 0.005), student as professional status (p≤0.005) and living in fewer poor neighborhoods located far from city centers (p = 0.030) were four conditions independently associated with sedentary/inactive and/or sedentary/active profiles. Based on these findings, to help reduce SIH, we used a typology of actions based on the underlying theoretical interventions including four main action categories: strengthening individuals (using person-based strategies), strengthening communities, improving living and working conditions, and promoting health-based macro-policies. Our findings suggest several directions for reducing lifestyle risk factors and enhancing T2D primary prevention programs targeting psychosocial, behavioral, and structural exposures.

White meat consumption and risk of cardiovascular disease and type 2 diabetes: a systematic review and meta-analysis.

The aim was to systematically review the associations among white meat consumption, cardiovascular diseases (CVD), and type 2 diabetes (T2D). Databases MEDLINE, Embase, and Cochrane Central Register of Controlled Trials and Scopus were searched (15th October 2021) for randomized intervention trials (RCTs, ≥ 4 weeks of duration) and prospective cohort studies (≥12 month of follow-up) assessing the consumption of white meat as the intervention/exposure. Eligible outcomes for RCTs were cardiometabolic risk factors and for cohorts, fatal and non-fatal CVD and incident T2D. Risk of bias was estimated using the Cochrane's RoB2 and Risk of Bias for Nutrition Observational Studies. Meta-analysis was conducted in case of ≥3 relevant intervention studies or ≥5 cohort studies using random-effects models. The strength of evidence was evaluated using the World Cancer Research Fund's criteria. The literature search yielded 5,795 scientific articles, and after screening 43 full-text articles, 23 cohort studies and three intervention studies were included. All included intervention studies matched fat content of intervention and control diets, and none of them showed any significant effects on the selected outcomes of white meat when compared to red meat. Findings from the cohort studies generally did not support any associations between white meat intake and outcomes. Meta-analyses were conducted for CVD mortality (RR: 0.95, 95% CI: 0.87-1.02, P = 0.23, I2 = 25%) and T2D incidence (RR: 0.98, 95% CI: 0.87-1.11, P = 0.81, I2 = 82%). The currently available evidence does not indicate a role, beneficial or detrimental, of white meat consumption for CVD and T2D. Future studies investigating potentially different health effects of processed versus unprocessed white meat and substitution of red meat with white meat are warranted.Registration: Prospero registration CRD42022295915.

Non Alcoholic Fatty Liver Disease (NAFLD) – An Emerging Challenge

A rapidly emerging cause of Chronic Liver Disease (CLD) is Non-alcoholic Fatty Liver Disease (NAFLD). In the West, the prevalence of NAFLD is as high as 30% and it is postulated that it may affect one-third of the population by 2030 [1]. Various studies have shown that the prevalence of NAFLD in Pakistan ranges from 14% to 47% [2]. The spectrum of liver damage in NAFLD is wide-ranging and essentially involves non-alcoholic causes of fat accumulation in the cells of the liver. This can also occur in other conditions where there is more than 5% steatosis. These conditions include chronic liver disease (CLD) caused by drugs (such as Methotrexate, Amiodarone, Tamoxifen etc.) or viruses (such as HCV), exposure to environmental toxins, malnutrition, hemochromatosis, Wilson’s disease, and any autoimmune disease triggering 5% steatosis [3]. There is a strong association of NAFLD with obesity (in more than 40% of patients) [4], hypertriglyceridemia (in 20% or more), diabetes mellitus (in 20% or more), and insulin resistance – all components of the metabolic syndrome [5]. Over the last two decades, rising trends of DM, obesity and insulin resistance have gone hand in hand with increasing prevalence of NAFLD [6]. Pakistan has a 17.1% incidence of Type-2 diabetes and a 14% incidence of NAFLD. There is a 32% incidence of NAFLD in Pakistani type 2 diabetics [7]. The National Health Survey of Pakistan conducted way back in 2006 depicted an incidence of obesity in 25% of the Pakistani population, and since then, numbers have continued to rise.

Combined effect of adiposity and elevated inflammation on incident type 2 diabetes: a prospective cohort study

BackgroundAdiposity and elevated inflammation are two hallmarks of hyperglycemia. However, it is unknown whether clustering of elevated inflammation and adiposity interact act on diabetogenesis and lead to a greater risk for incident type 2 diabetes (T2D).MethodsAdiposity was indicated by body mass index, waist circumference and ultrasonography-measured fatty liver degrees. Elevated inflammation was indicated as high-sensitivity C-reactive protein levels ≥ 2 mg/L. Time-to-event survival analyses were conducted to investigate the joint effect of adiposity and inflammation on incident T2D on both multiplicative and additive scales.ResultsAmong 82,172 non-diabetic participants from a prospective cohort in China, 14,278 T2D occurred over a median follow-up of 11 years. In the multivariable-adjusted model, elevated inflammation [1.12 (1.08‒1.16)] and adiposity [1.76 (1.69‒1.83) for overweight/obesity, 1.49 (1.44‒1.55) for central obesity, and 2.02 (1.95‒2.09) for fatty liver] were significantly associated with incident diabetes. Higher adiposity-associated risks and incidence rates of diabetes were observed with elevated inflammation. When studying the joint effect, the adjusted HRs were 1.77 (1.69‒1.85) for overweight/obesity, 1.14 (1.06‒1.23) for elevated inflammation, and 2.08 (1.97‒2.19) for their joint effect, with a relative excess risk due to interaction of 0.17 (0.05‒0.28). The attributable proportions were 71.30% for overweight/obesity, 12.96% for elevated inflammation, and 15.74% for their interaction. Similar results were observed when adiposity was assessed as waist circumference or fatty liver.ConclusionsAdiposity and elevated inflammation synergically lead to greater risks of incident diabetes than addition of each individual exposure. Strategies simultaneously targeting both risks should produce more benefits for diabetes prevention than through initiatives directed at each separate risk.

Effect of denosumab on glucose metabolism in postmenopausal osteoporotic women with prediabetes: a study protocol for a 12-month multicenter, open-label, randomized controlled trial

BackgroundParticipants with prediabetes are at a high risk of developing type 2 diabetes (T2D). Recent studies have suggested that blocking the receptor activator of nuclear factor-κB ligand (RANKL) may improve glucose metabolism and delay the development of T2D. However, the effect of denosumab, a fully human monoclonal antibody that inhibits RANKL, on glycemic parameters in the prediabetes population is uncertain. We aim to examine the effect of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes.MethodsThis is a 12-month multicenter, open-label, randomized controlled trial involving postmenopausal women who have been diagnosed with both osteoporosis and prediabetes. Osteoporosis is defined by the World Health Organization (WHO) as a bone mineral density T score of ≤ − 2.5, as measured by dual-energy X-ray absorptiometry (DXA). Prediabetes is defined as (i) a fasting plasma glucose level of 100–125 mg/dL, (ii) a 2-hour plasma glucose level of 140–199 mg/dL, or (iii) a glycosylated hemoglobin A1c (HbA1c) level of 5.7–6.4%. A total of 346 eligible subjects will be randomly assigned in a 1:1 ratio to receive either subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg every week for 12 months. The primary outcome is the change in HbA1c levels from baseline to 12 months. Secondary outcomes include changes in fasting and 2-hour blood glucose levels, serum insulin levels, C-peptide levels, and insulin sensitivity from baseline to 12 months, and the incidence of T2D at the end of the study. Follow-up visits will be scheduled at 3, 6, 9, and 12 months.DiscussionThis study aims to provide evidence on the efficacy of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. The results derived from this clinical trial may provide insight into the potential of denosumab in preventing T2D in high-risk populations.Trial registrationThis study had been registered in the Chinese Clinical Trials Registry. Registration number: ChiCTR2300070789 on April 23, 2023. https://www.chictr.org.cn.

Olive oil consumption, plasma metabolites, and risk of type 2 diabetes and cardiovascular disease

BackgroundOlive oil consumption has been inversely associated with the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, the impact of olive oil consumption on plasma metabolites remains poorly understood. This study aims to identify plasma metabolites related to total and specific types of olive oil consumption, and to assess the prospective associations of the identified multi-metabolite profiles with the risk of T2D and CVD.MethodsThe discovery population included 1837 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) trial with available metabolomics data at baseline. Olive oil consumption was determined through food-frequency questionnaires (FFQ) and adjusted for total energy. A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation sample. Plasma metabolomics analyses were performed using LC–MS. Cross-sectional associations between 385 known candidate metabolites and olive oil consumption were assessed using elastic net regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite-weighted models and FFQ-derived olive oil consumption in each pair of training–validation data sets within the discovery sample. We further estimated the prospective associations of the identified plasma multi-metabolite profile with incident T2D and CVD using multivariable Cox regression models.ResultsWe identified a metabolomic signature for the consumption of total olive oil (with 74 metabolites), VOO (with 78 metabolites), and COO (with 17 metabolites), including several lipids, acylcarnitines, and amino acids. 10-CV Pearson correlation coefficients between total olive oil consumption derived from FFQs and the multi-metabolite profile were 0.40 (95% CI 0.37, 0.44) and 0.27 (95% CI 0.22, 0.31) for the discovery and validation sample, respectively. We identified several overlapping and distinct metabolites according to the type of olive oil consumed. The baseline metabolite profiles of total and extra virgin olive oil were inversely associated with CVD incidence (HR per 1SD: 0.79; 95% CI 0.67, 0.92 for total olive oil and 0.70; 0.59, 0.83 for extra virgin olive oil) after adjustment for confounders. However, no significant associations were observed between these metabolite profiles and T2D incidence.ConclusionsThis study reveals a panel of plasma metabolites linked to the consumption of total and specific types of olive oil. The metabolite profiles of total olive oil consumption and extra virgin olive oil were associated with a decreased risk of incident CVD in a high cardiovascular-risk Mediterranean population, though no associations were observed with T2D incidence.Trial registration: The PREDIMED trial was registered at ISRCTN (http://www.isrctn.com/, ISRCTN35739639).

Vaspin: A Novel Biomarker Linking Gluteofemoral Body Fat and Type 2 Diabetes Risk.

To determine whether adiposity depots modulate vaspin levels and whether vaspin predicts type 2 diabetes (T2D) risk, through epidemiological and genetic analyses. We assessed the relationship of plasma vaspin concentration with incident and prevalent T2D and adiposity-related variables in 1) the Prospective Urban and Rural Epidemiology (PURE) biomarker substudy (N = 10,052) and 2) the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial (N = 7,840), using regression models. We then assessed whether vaspin is causally associated with T2D and whether genetic variants associated with MRI-measured adiposity depots modulate vaspin levels, using two-sample Mendelian randomization (MR). A 1-SD increase in circulating vaspin levels was associated with a 16% increase in incident T2D in the PURE cohort (hazard ratio 1.16; 95% CI 1.09-1.23; P = 4.26 × 10-7) and prevalent T2D in the ORIGIN cohort (odds ratio [OR] 1.16; 95% CI 1.07-1.25; P = 2.17 × 10-4). A 1-unit increase in BMI and triglyceride levels was associated with a 0.08-SD (95% CI 0.06-0.10; P = 2.04 × 10-15) and 0.06-SD (95% CI 0.04-0.08; P = 4.08 × 10-13) increase, respectively, in vaspin in the PURE group. Consistent associations were observed in the ORIGIN cohort. MR results reinforced the association between vaspin and BMI-adjusted T2D risk (OR 1.01 per 1-SD increase in vaspin level; 95% CI 1.00-1.02; P = 2.86 × 10-2) and showed that vaspin was increased by 0.10 SD per 1-SD decrease in genetically determined gluteofemoral adiposity (95% CI 0.02-0.18; P = 2.01 × 10-2). No relationships were found between subcutaneous or visceral adiposity and vaspin. These findings support that higher vaspin levels are related to increased T2D risk and reduced gluteofemoral adiposity, positioning vaspin as a promising clinical predictor for T2D.

Plasma Metabolites Related to the Consumption of Different Types of Dairy Products and Their Association with New-Onset Type 2 Diabetes: Analyses in the Fenland and EPIC-Norfolk Studies, United Kingdom.

To identify metabolites associated with habitual dairy consumption and investigate their associations with type 2 diabetes (T2D) risk. Metabolomics assays were conducted in the Fenland (n = 10,281) and EPIC-Norfolk (n = 1,440) studies. Using 82 metabolites assessed in both studies, we developed metabolite scores to classify self-reported consumption of milk, yogurt, cheese, butter, and total dairy (Fenland Study-discovery set; n = 6035). Internal and external validity of the scores was evaluated (Fenland-validation set, n = 4246; EPIC-Norfolk, n = 1440). The study assessed associations between each metabolite score and T2D incidence in EPIC-Norfolk (n = 641 cases; 16,350 person-years). The scores classified low and high consumers for all dairy types with internal validity, and milk, butter, and total dairy with external validity. The scores were further associated with lower incident T2D: hazard ratios (95% confidence interval) per standard deviation: milk 0.71 (0.65, 0.77); butter 0.62 (0.57, 0.68); total dairy 0.66 (0.60, 0.72). These associations persisted after adjustment for known dairy-fat biomarkers. Metabolite scores identified habitual consumers of milk, butter, and total dairy products, and were associated with lower T2D risk. These findings hold promise for identifying objective indicators of the physiological response to dairy consumption.

Incidence of type 2 diabetes before and during the COVID-19 pandemic in Naples, Italy: a longitudinal cohort study

The association of COVID-19 with the development of new-onset diabetes has been recently investigated by several groups, yielding controversial results. Population studies currently available in the literature are mostly focused on type 1 diabetes (T1D), comparing patients with a SARS-CoV-2 positive test to individuals without COVID-19, especially in paediatric populations. In this study, we sought to determine the incidence of type 2 diabetes (T2D) before and during the COVID-19 pandemic. In this longitudinal cohort study, we analysed a cohort followed up over a 6-year period using an Interrupted Time Series approach, i.e. 3-years before and 3-years during the COVID-19 pandemic. We analysed data obtained from >200,000 adults in Naples (Italy) from January 1st 2017 to December 31st 2022. In this manner, we had the opportunity to compare the incidence of newly diagnosed T2D before (2017-2019) and during (2020-2022) the COVID-19 pandemic. The key inclusion criteria were age >18-year-old and data availability for the period of observation; patients with a diagnosis of diabetes obtained before 2017 were excluded. The main outcome of the study was the new diagnosis of T2D, as defined by the International Classification of Diseases 10 (ICD-X), including prescription of antidiabetic therapies for more than 30 days. A total of 234,956 subjects were followed-up for at least 3-years before or 3-years during the COVID-19 pandemic and were included in the study; among these, 216,498 were analysed in the pre-pandemic years and 216,422 in the pandemic years. The incidence rate of T2D was 4.85 (95% CI, 4.68-5.02) per 1000 person-years in the period 2017-2019, vs 12.21 (95% CI, 11.94-12.48) per 1000 person-years in 2020-2022, with an increase of about twice and a half. Moreover, the doubling time of the number of new diagnoses of T2D estimated by unadjusted Poisson model was 97.12 (95% CI, 40.51-153.75) months in the prepandemic period vs 23.13 (95% CI, 16.02-41.59) months during the COVID-19 pandemic. Interestingly, these findings were also confirmed when examining patients with prediabetes. Our data from this 6-year study on more than 200,000 adult participants indicate that the incidence of T2D was significantly higher during the pandemic compared to the pre-COVID-19 phase. As a consequence, the epidemiology of the disease may change in terms of rates of outcomes as well as public health costs. COVID-19 survivors, especially patients with prediabetes, may require specific clinical programs to prevent T2D. The US National Institutes of Health (NIH: NIDDK, NHLBI, NCATS), Diabetes Action Research and Education Foundation, Weill-Caulier and Hirschl Trusts.

Diabetes Mellitus and Prevalence of Other Comorbid Conditions: A Systematic Review.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, severity continues to rise worldwide. This systematic review seeks to examine the prevalence of diabetes and its associated comorbid conditions, aiming to provide insights into the multifaceted impact of diabetes on a broader scale. DM exhibits a positive correlation with advancing age, and it's strongly influenced by genetic predisposition. In recent years, there has been a discernible global increase in the prevalence of type 1 diabetes (T1D), as evidenced by extensive epidemiological studies. Individuals with DM frequently have a positive familial history, and the presence of DM in both parents or solely the mother significantly amplifies genetic susceptibility. Moreover, non-genetic factors, such as acute psychological stressors, obesity, pregnancy, and smoking play a pivotal role in the development of DM. Notably, urinary tract infections (UTIs) are a common comorbidity in patients with type 2 diabetes (T2D) and all patients with T1D. T2D is prevalent, particularly among females, and its incidence rises with age. UTIs are prevalent among individuals with diabetes, particularly females, with Escherichia coli (E. coli) isolates being the primary etiological agents responsible for UTI inflammation. Insulin resistance is a common feature in both prediabetes and prehypertension, serving as a precursor to these conditions. The increasing incidence of T2D in regions with high tuberculosis (TB) prevalence emphasizes the significance of understanding DM as a substantial TB risk factor. DM is associated with a threefold elevation in TB risk and a twofold increase in unfavorable outcomes during TB treatment. Notably, the global prevalence of DM has led to a larger population of TB patients with comorbid DM than TB patients coinfected with HIV. Diabetes and sepsis contribute significantly to worldwide morbidity and mortality, with diabetic individuals experiencing more post-sepsis complications and increased mortality. The coexistence of hypertension and T2D is a common comorbidity, with hypertension incidence being twice as high among individuals with diabetes compared to those without, often linked to insulin resistance and a heightened risk of diabetes onset.

Substitution of animal-based with plant-based foods on cardiometabolic health and all-cause mortality: a systematic review and meta-analysis of prospective studies

BackgroundThere is growing evidence that substituting animal-based with plant-based foods is associated with a lower risk of cardiovascular diseases (CVD), type 2 diabetes (T2D), and all-cause mortality. Our aim was to summarize and evaluate the evidence for the substitution of any animal-based foods with plant-based foods on cardiometabolic health and all-cause mortality in a systematic review and meta-analysis.MethodsWe systematically searched MEDLINE, Embase, and Web of Science to March 2023 for prospective studies investigating the substitution of animal-based with plant-based foods on CVD, T2D, and all-cause mortality. We calculated summary hazard ratios (SHRs) and 95% confidence intervals (95% CI) using random-effects meta-analyses. We assessed the certainty of evidence (CoE) using the GRADE approach.ResultsIn total, 37 publications based on 24 cohorts were included. There was moderate CoE for a lower risk of CVD when substituting processed meat with nuts [SHR (95% CI): 0.73 (0.59, 0.91), n = 8 cohorts], legumes [0.77 (0.68, 0.87), n = 8], and whole grains [0.64 (0.54, 0.75), n = 7], as well as eggs with nuts [0.83 (0.78, 0.89), n = 8] and butter with olive oil [0.96 (0.95, 0.98), n = 3]. Furthermore, we found moderate CoE for an inverse association with T2D incidence when substituting red meat with whole grains/cereals [0.90 (0.84, 0.96), n = 6] and red meat or processed meat with nuts [0.92 (0.90, 0.94), n = 6 or 0.78 (0.69, 0.88), n = 6], as well as for replacing poultry with whole grains [0.87 (0.83, 0.90), n = 2] and eggs with nuts or whole grains [0.82 (0.79, 0.86), n = 2 or 0.79 (0.76, 0.83), n = 2]. Moreover, replacing red meat for nuts [0.93 (0.91, 0.95), n = 9] and whole grains [0.96 (0.95, 0.98), n = 3], processed meat with nuts [0.79 (0.71, 0.88), n = 9] and legumes [0.91 (0.85, 0.98), n = 9], dairy with nuts [0.94 (0.91, 0.97), n = 3], and eggs with nuts [0.85 (0.82, 0.89), n = 8] and legumes [0.90 (0.89, 0.91), n = 7] was associated with a reduced risk of all-cause mortality.ConclusionsOur findings indicate that a shift from animal-based (e.g., red and processed meat, eggs, dairy, poultry, butter) to plant-based (e.g., nuts, legumes, whole grains, olive oil) foods is beneficially associated with cardiometabolic health and all-cause mortality.

Role of Gut Microbiota in Statin-Associated New-Onset Diabetes-A Cross-Sectional and Prospective Analysis of the FINRISK 2002 Cohort.

Dyslipidemia is treated effectively with statins, but treatment has the potential to induce new-onset type-2 diabetes. Gut microbiota may contribute to this outcome variability. We assessed the associations of gut microbiota diversity and composition with statins. Bacterial associations with statin-associated new-onset type-2 diabetes (T2D) risk were also prospectively evaluated. We examined shallow-shotgun-sequenced fecal samples from 5755 individuals in the FINRISK-2002 population cohort with a 17+-year-long register-based follow-up. Alpha-diversity was quantified using Shannon index and beta-diversity with Aitchison distance. Species-specific differential abundances were analyzed using general multivariate regression. Prospective associations were assessed with Cox regression. Applicable results were validated using gradient boosting. Statin use associated with differing taxonomic composition (R2, 0.02%; q=0.02) and 13 differentially abundant species in fully adjusted models (MaAsLin; q<0.05). The strongest positive association was with Clostridium sartagoforme (β=0.37; SE=0.13; q=0.02) and the strongest negative association with Bacteroides cellulosilyticus (β=-0.31; SE=0.11; q=0.02). Twenty-five microbial features had significant associations with incident T2D in statin users, of which only Bacteroides vulgatus (HR, 1.286 [1.136-1.457]; q=0.03) was consistent regardless of model adjustment. Finally, higher statin-associated T2D risk was seen with [Ruminococcus] torques (ΔHRstatins, +0.11; q=0.03), Blautia obeum (ΔHRstatins, +0.06; q=0.01), Blautia sp. KLE 1732 (ΔHRstatins, +0.05; q=0.01), and beta-diversity principal component 1 (ΔHRstatin, +0.07; q=0.03) but only when adjusting for demographic covariates. Statin users have compositionally differing microbiotas from nonusers. The human gut microbiota is associated with incident T2D risk in statin users and possibly has additive effects on statin-associated new-onset T2D risk.

Incidence of depression in type 2 diabetes patients with and without cardiovascular disease

Abstract Background Information on how subtypes of incident cardiovascular disease (CVD) affect the rate of depression in patients with type 2 diabetes (T2D) can help identity high-risk patients. Purpose To compare the incidence of depression among patients with T2D with incident CVD relative to patients with T2D free of CVD but similar duration of T2D. Methods Patients diagnosed with incident T2D without CVD or psychiatric disease were identified from the Danish registries between 2000 and 2018. CVD was defined as the first diagnosis of acute myocardial infarction (AMI), heart failure (HF), stroke, or peripheral artery disease (PAD). The patients were followed 90 days after first T2D diagnosis until first occurrence of depression, emigration, death, one year after CVD development, or end of the study (December 31, 2019). We used time-dependent Poisson regression to estimate the incidence rate ratios (IRR) of depression following different types of CVD compared with patients without CVD. The model included age, sex, comorbidities, calendar year, T2D duration, educational level, and living situation as covariates. Results Among 175,916 incident T2D patients (median age 61 (IQR:51;70), 59% males) followed for 1,306,228 person-years (py), 34,825 experienced depression. The crude incidence rate of depression per 1000 py (95% confidence interval) in patients without CVD was 25.8 (16.8;37.9). Compared with T2D patients without CVD, adjusted IRR of depression following AMI, stroke, PAD, and HF was: 2.4 (1.8;3.1) 5.7 (5.3;6.2), 2.5 (2.2;2.9), 2.3 (2.1;2.6), respectively. Conclusions All CVDs was associated with increased rate of depression, but highest rate was seen in T2D patients with stroke.

Triglycerides/HDL cholesterol ratio and type 2 diabetes incidence: Panasonic Cohort Study 10

BackgroundPrevious studies have investigated the association between the ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) and the incidence of diabetes in adults and discovered that a high TG/HDL-C ratio was linked to an elevated risk of new-onset diabetes. However, the comparison of predicting diabetes development among lipid profiles including the TG/HDL-C ratio, and the ratio of TG/HDL-C cut-off value has received limited attention. We examined the relationship between diabetes onset and the TG/HDL-C ratio in addition to the applicable cut-off value for predicting diabetes onset.MethodsThis study included 120,613 participants from the health examination database at Panasonic Corporation from 2008 to 2017. Cox regression analysis employing multivariable models was used to investigate the association between lipid profiles, particularly the ratio of TG/HDL-C and the development of type 2 diabetes (T2D). The multivariable model was adjusted for age, sex, BMI, systolic blood pressure, plasma glucose levels after fasting, smoking status, and exercise habits. Areas under time-dependent receiver operating characteristic (ROC) curves (AUCs) were employed to assess the prediction performance and cut-off values of each indicator. A fasting plasma glucose level of 126 mg/dL, a self-reported history of diabetes, or usage of antidiabetic medicines were used to identify T2D.ResultsDuring the course of the study, 6,080 people developed T2D. The median follow-up duration was 6.0 (3–10) years. Multivariable analysis revealed that the ratio of TG/HDL-C (per unit, HR; 1.03 [95% CI 1.02–1.03]) was substantially linked to the risk of incident T2D. AUC and cut-off points for the ratio of TG/HDL-C for T2D development after 10 years were 0.679 and 2.1, respectively. Furthermore, the AUC of the ratio of TG/HDL-C was considerably larger compared to that of LDL-C, HDL-C, and TG alone (all P < 0.001). We discovered an interaction effect between sex, BMI, and lipid profiles in subgroup analysis. Females and participants having a BMI of < 25 kg/m2 showed a higher correlation between lipid profile levels and T2D onset.ConclusionsThe ratio of TG/HDL-C was found to be a stronger predictor of T2D development within 10 years than LDL-C, HDL-C, or TG, indicating that it may be useful in future medical treatment support.