Association Between the EAT-Lancet Diet Pattern and Risk of Type 2 Diabetes: A Prospective Cohort Study

Background:The EAT-Lancet Commission has promulgated a sustainable dietary guideline and recommended that it was designed to improve the human health and support environmental sustainability.Objective:This research was designed to explore the association between this healthy diet pattern (EAT-Lancet diet pattern, EAT-LDP) and risk of type 2 diabetes (T2D).Methods:Between 2006 and 2010, a total of 59,849 participants from the UK Biobank without diabetes, cardiovascular disease, or cancers were included at baseline. The EAT-LDP score was constructed on the sum of 14 food components and then categorized into three tertiles. Multivariable Cox proportional hazards regression models were conducted to explore the association between EAT-LDP score and the risk of incident T2D. A mediation analysis was also implemented to disentangle the role of body mass index (BMI) and waist circumference in the relationship between EAT-LDP score and T2D.Results:During a median follow-up of 10 years, 2,461 incident T2D cases were recorded. In analyses that compared tertile 3 of the EAT-LDP score (highest) with tertile 1 (lowest), the hazard ratio (HR) for T2D was 0.81 (95% CI: 0.72–0.90) after adjusting for sociodemographic status and health-related factors. Participants who reported a one-point increase in the diet score were associated with a 6% decrease in risk of T2D (HR: 0.94, 95% CI: 0.91–0.97). A significant indirect association was observed between the EAT-LDP score and T2D (β: 0.66, 95% CI: 0.65–0.67), indicating that 44% of the association of EAT-LDP score with T2D was mediated by BMI. Additionally, 40% of the association of EAT-LDP score with T2D was mediated by waist circumference was also observed.Conclusions:Our findings indicate that a higher adherence to EAT-LDP contributes to lower risk of T2D. Further independent validation is needed to be conducted before applying the EAT-LDP to inform dietary guidelines.

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Associations of Diet Quality and All-Cause Mortality Across Levels of Cardiometabolic Health and Disease: A 7.6-Year Prospective Analysis From the Dutch Lifelines Cohort

10.2337/figshare.13964039 ◽

2021 ◽

Author(s):

Petra C Vinke ◽

Gerjan Navis ◽

Daan Kromhout ◽

Eva Corpeleijn

Keyword(s):

Type 2 Diabetes ◽

Diet Quality ◽

Total Population ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Dietary Guidelines ◽

Cardiometabolic Health ◽

Ageing Population ◽

All Cause Mortality

Objective: To simultaneously investigate the association of diet quality and all-cause mortality in groups with varying cardiometabolic diseases (CMDs) at baseline. Design: From the population-based Lifelines cohort, 40,892 non-underweight participants aged ≥50 years with data on diet quality and confounding factors were included (enrollment 2006-2013). From food frequency questionnaire data, tertiles of the Lifelines diet score were calculated (T1 = poorest, T3 = best diet quality). Four CMD categories were defined: 1) CMD-free, 2) type 2 diabetes, 3) one cardiovascular disease (CVD), 4) two or more CMDs. Months when deaths occurred were obtained from municipal registries up until November 2019. Multivariable Cox proportional hazards models were applied for the total population and stratified by CMD categories. Results: After a median follow-up of 7.6 years, 1,438 participants died. Diet quality and CMD categories were independently associated with all-cause mortality in crude and adjusted models (p < 0.001). A dose-response relationship of diet quality with all-cause mortality was observed in the total population (P for trend < 0.001, T2 vs. T3 = 1.22 (1.07-1.41), T1 vs. T3 = 1.57 (1.37-1.80)). In stratified analyses, the association was significant for CMD-free individuals (T1 vs. T3 = 1.63 (1.38-1.93)) and for type 2 diabetes patients (1.87 (1.17-3.00)), but not for patients with one CVD (1.39 (0.93-2.08)) or multiple CMDs (1.19 (0.80-1.76)). Conclusions: A high-quality diet can potentially lower all-cause mortality risk in the majority of the ageing population. Its effect may be greatest for CMD-free individuals and patients with type 2 diabetes. Tailored dietary guidelines may be required for patients with extensive histories of CMDs.

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Associations of Diet Quality and All-Cause Mortality Across Levels of Cardiometabolic Health and Disease: A 7.6-Year Prospective Analysis From the Dutch Lifelines Cohort

10.2337/figshare.13964039.v1 ◽

2021 ◽

Author(s):

Petra C Vinke ◽

Gerjan Navis ◽

Daan Kromhout ◽

Eva Corpeleijn

Keyword(s):

Type 2 Diabetes ◽

Diet Quality ◽

Total Population ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Dietary Guidelines ◽

Cardiometabolic Health ◽

Ageing Population ◽

All Cause Mortality

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Habitual snoring, adiposity measures and risk of type 2 diabetes in 0.5 million Chinese adults: a 10-year cohort

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-001015 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001015

Author(s):

Yuxia Wei ◽

Bang Zheng ◽

Junning Fan ◽

Jun Lv ◽

Yu Guo ◽

...

Keyword(s):

Type 2 Diabetes ◽

Waist Circumference ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Healthy Weight ◽

Chinese Adults ◽

Habitual Snoring ◽

Cox Proportional Hazards Models ◽

Joint Influence

ObjectivesThe present study aimed to examine whether habitual snoring was independently associated with risk of type 2 diabetes among Chinese adults, and to assess the role that adiposity measures play in the snoring–diabetes association, as well as to evaluate the joint influence of snoring and adiposity measures on diabetes.Research design and methodsThe China Kadoorie Biobank study recruited 512 715 adults aged 30–79 years from 10 regions in China during 2004 and 2008. Data from 482 413 participants without baseline diabetes were analyzed in the present study. Autoregressive cross-lagged panel analysis was used to assess the longitudinal relationship between adiposity measures and habitual snoring. Cox proportional hazards models were used to examine the association between habitual snoring and diabetes risk.ResultsBoth higher body mass index and waist circumference were associated with higher risks of subsequent habitual snoring, whereas no reverse association was detected. A total of 16 479 type 2 diabetes cases were observed during a 10-year follow-up. Habitual snoring was independently associated with 12% (95% CI 6% to 18%) and 14% (95% CI 9% to 19%) higher risks of diabetes among men and women, respectively. Habitual snorers who had general obesity or central obesity were about twice as likely to develop diabetes as non-snorers at the lowest levels of adiposity measures.ConclusionHabitual snoring was independently associated with a higher risk of type 2 diabetes among Chinese adults. It is important to maintain both a healthy weight and a normal waist circumference to prevent or alleviate habitual snoring and ultimately prevent diabetes among Chinese adults.

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Association Between Change in Accelerometer-Measured and Self-Reported Physical Activity and Cardiovascular Disease in the Look AHEAD Trial

10.2337/figshare.17157926 ◽

2022 ◽

Author(s):

John M. Jakicic ◽

Robert I. Berkowitz ◽

Paula Bolin ◽

George A. Bray ◽

Jeanne M. Clark ◽

...

Keyword(s):

Physical Activity ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Proportional Hazards ◽

Secondary Analysis ◽

Cox Proportional Hazards ◽

Self Report ◽

Look Ahead ◽

The Look

OBJECTIVE: To conduct post-hoc secondary analysis examining the association between change in physical activity (PA), measured with self-report and accelerometry, from baseline to 1 and 4 years and cardiovascular disease (CVD) outcomes in the Look AHEAD Trial. RESEARCH DESIGN AND METHODS: Participants were adults with overweight/obesity and type 2 diabetes with PA data at baseline and year 1 or 4 (n = 1,978). Participants were randomized to diabetes support and education or intensive lifestyle intervention. Measures included accelerometry-measured moderate-to-vigorous PA (MVPA), self-reported PA, and composite (morbidity and mortality) CVD outcomes. RESULTS: In pooled analyses of all participants, using Cox proportional hazards models, each 100 MET-min/wk increase in accelerometry-measured MVPA from baseline to 4 years was associated with decreased risk of the subsequent primary composite outcome of CVD. Results were consistent for changes in total MVPA [HR=0.97 (95% CI: 0.95, 0.99)] and MVPA accumulated in >10-minute bouts [HR=0.95 (95% CI: 0.91, 0.98)], with a similar pattern for secondary CVD outcomes. Change in accelerometry-measured MVPA at 1 year and self-reported change in PA at 1 and 4 years were not associated with CVD outcomes. CONCLUSIONS: Increased accelerometry-measured MVPA from baseline to year 4 is associated with decreased risk of CVD outcomes. This suggests the need for long-term engagement in MVPA to reduce the risk of CVD in adults with overweight/obesity and type 2 diabetes.

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Pioglitazone and cause-specific risk of mortality in patients with type 2 diabetes: extended analysis from a European multidatabase cohort study

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2017-000481 ◽

2018 ◽

Vol 6 (1) ◽

pp. e000481 ◽

Cited By ~ 9

Author(s):

Helen Strongman ◽

Solomon Christopher ◽

Maila Majak ◽

Rachael Williams ◽

Shahram Bahmanyar ◽

...

Keyword(s):

Type 2 Diabetes ◽

Propensity Score ◽

Cardiovascular Mortality ◽

Proportional Hazards ◽

Cohort Analysis ◽

Cox Proportional Hazards ◽

Exposed Group ◽

Mortality Data ◽

Exact Matching

ObjectivesDescribe and compare the risk of cardiovascular and non-cardiovascular mortality in patients whose antidiabetic therapy is modified to include pioglitazone compared with an alternative antidiabetic medication at the same stage of disease progression.Research design and methodsThis exploratory linked database cohort analysis used pooled health and mortality data from three European countries: Finland, Sweden and the UK. Propensity score together with exact matching was used to match 31 133 patients with type 2 diabetes first prescribed pioglitazone from 2000 to 2011, to 31 133 patients never prescribed pioglitazone. Exact matching variables were treatment stage, history of diabetes, diabetes complications and cardiovascular disease, and year of cohort entry. Mean follow-up time was 2.60 (SD 2.00) and 2.69 (SD 2.31) years in the pioglitazone and non-pioglitazone-exposed groups, respectively. Crude cause-specific mortality rates were ascertained. Association with pioglitazone use was estimated using Cox proportional hazards models adjusted a priori for country, age, sex, the propensity score quintile and time-dependent variables representing use of antidiabetic drugs. Stepwise testing identified no additional confounders to include in adjusted models.ResultsThe crude mortality rate was lower in the pioglitazone-exposed group than the non-exposed group for both cardiovascular and non-cardiovascular mortality. Adjusted HRs comparing pioglitazone to alternative antidiabetic exposure were 0.58 (95% CI 0.52 to 0.63) and 0.63 (95% CI 0.58 to 0.68) for cardiovascular and non-cardiovascular mortality, respectively. A protective effect associated with pioglitazone was also found for all specific cardiovascular causes.ConclusionsThis analysis suggests that pioglitazone is associated with a decrease in both cardiovascular and non-cardiovascular mortality. Results should be interpreted with caution due to the potential for residual confounding in this exploratory analysis. Further studies, specifically designed to test the association between pioglitazone use and patient-focused outcomes, are suggested.Study registration numberEuropean Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP; EUPAS3626).

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High Betaine, a Trimethylamine N-Oxide Related Metabolite, Is Prospectively Associated with Low Future Risk of Type 2 Diabetes Mellitus in the PREVEND Study

Journal of Clinical Medicine ◽

10.3390/jcm8111813 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1813 ◽

Cited By ~ 2

Author(s):

Erwin Garcia ◽

Maryse C. J. Osté ◽

Dennis W. Bennett ◽

Elias J. Jeyarajah ◽

Irina Shalaurova ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Regression ◽

Proportional Hazards Regression ◽

Study Results ◽

Future Risk

Background: Gut microbiota-related metabolites, trimethylamine-N-oxide (TMAO), choline, and betaine, have been shown to be associated with cardiovascular disease (CVD) risk. Moreover, lower plasma betaine concentrations have been reported in subjects with type 2 diabetes mellitus (T2DM). However, few studies have explored the association of betaine with incident T2DM, especially in the general population. The goals of this study were to evaluate the performance of a newly developed betaine assay and to prospectively explore the potential clinical associations of betaine and future risk of T2DM in a large population-based cohort. Methods: We developed a high-throughput, nuclear magnetic resonance (NMR) spectroscopy procedure for acquiring spectra that allow for the accurate quantification of plasma/serum betaine and TMAO. Assay performance for betaine quantification was assessed and Cox proportional hazards regression was employed to evaluate the association of betaine with incident T2DM in 4336 participants in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Results: Betaine assay results were linear (y = 1.02X − 3.75) over a wide range of concentrations (26.0–1135 µM). The limit of blank (LOB), limit of detection (LOD) and limit of quantitation (LOQ) were 6.4, 8.9, and 13.2 µM, respectively. Coefficients of variation for intra- and inter-assay precision ranged from 1.5–4.3% and 2.5–5.5%, respectively. Deming regression analysis of results produced by NMR and liquid chromatography coupled to tandem mass spectrometry(LC-MS/MS) revealed an R2 value of 0.94 (Y = 1.08x – 1.89) and a small bias for higher values by NMR. The reference interval, in a cohort of apparently healthy adult participants (n = 501), was determined to be 23.8 to 74.7 µM (mean of 42.9 ± 12.6 µM). In the PREVEND study (n = 4336, excluding subjects with T2DM at baseline), higher betaine was associated with older age and lower body mass index, total cholesterol, triglycerides, and hsCRP. During a median follow-up of 7.3 (interquartile range (IQR), 5.9–7.7) years, 224 new T2DM cases were ascertained. Cox proportional hazards regression models revealed that the highest tertile of betaine was associated with a lower incidence of T2DM. Hazard ratio (HR) for the crude model was 0.61 (95% CI: 0.44–0.85, p = 0.004). The association remained significant even after adjusting for multiple clinical covariates and T2DM risk factors, including fasting glucose. HR for the fully-adjusted model was 0.50 (95% CI: 0.32–0.80, p = 0.003). Conclusions: The newly developed NMR-based betaine assay exhibits performance characteristics that are consistent with usage in the clinical laboratory. Betaine levels may be useful for assessing the risk of future T2DM.

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Pain in Patients With Type 2 Diabetes-Related Polyneuropathy Is Associated With Vascular Events and Mortality

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa394 ◽

2020 ◽

Vol 105 (9) ◽

pp. 3005-3014

Author(s):

Brittany R Lapin ◽

Kevin M Pantalone ◽

Alex Milinovich ◽

Shannon Morrison ◽

Andrew Schuster ◽

...

Keyword(s):

Type 2 Diabetes ◽

Proportional Hazards ◽

Negative Binomial ◽

Cox Proportional Hazards ◽

Vascular Events ◽

Proportional Hazards Regression ◽

Increased Risk ◽

History Of ◽

Mortality Hazard Ratio

Abstract Purpose Type 2 diabetes–related polyneuropathy (DPN) is associated with increased vascular events and mortality, but determinants and outcomes of pain in DPN are poorly understood. We sought to examine the effect of neuropathic pain on vascular events and mortality in patients without DPN, DPN with pain (DPN + P), and DPN without pain (DPN-P). Methods A retrospective cohort study was conducted within a large health system of adult patients with type 2 diabetes from January 1, 2009 through December 31, 2016. Using an electronic algorithm, patients were classified as no DPN, DPN + P, or DPN-P. Primary outcomes included number of vascular events and time to mortality. Independent associations with DPN + P were evaluated using multivariable negative binomial and Cox proportional hazards regression models, adjusting for demographics, socioeconomic characteristics, and comorbidities. Results Of 43 945 patients with type 2 diabetes (age 64.6 ± 14.0 years; 52.1% female), 13 910 (31.7%) had DPN: 9104 DPN + P (65.4%) vs 4806 DPN-P (34.6%). Vascular events occurred in 4538 (15.1%) of no DPN patients, 2401 (26.4%) DPN + P, and 1006 (20.9%) DPN-P. After adjustment, DPN + P remained a significant predictor of number of vascular events (incidence rate ratio [IRR] = 1.55, 95% CI, 1.29-1.85), whereas no DPN was protective (IRR = 0.70, 95% CI, 0.60-0.82), as compared to DPN-P. Compared to DPN-P, DPN + P was also a significant predictor of mortality (hazard ratio = 1.42, 95% CI, 1.25-1.61). Conclusions Our study found a significant association between pain in DPN and an increased risk of vascular events and mortality. This observation warrants longitudinal study of the risk factors and natural history of pain in DPN.

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Increased Plasma DPP4 Activity Is Predictive of Prediabetes and Type 2 Diabetes Onset in Chinese Over a Four-Year Period: Result From the China National Diabetes and Metabolic Disorders Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-1480 ◽

2014 ◽

Vol 99 (11) ◽

pp. E2330-E2334 ◽

Cited By ~ 29

Author(s):

Tianpeng Zheng ◽

Yun Gao ◽

Attit Baskota ◽

Tao Chen ◽

Xingwu Ran ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Confidence Interval ◽

Proportional Hazards ◽

Chinese Women ◽

Linear Regression Analysis ◽

Multiple Linear Regression Analysis ◽

Cox Proportional Hazards ◽

Dipeptidyl Peptidase 4

Context: The significance of associations between prediabetes, type 2 diabetes, and dipeptidyl peptidase-4 (DPP4) activity in a Chinese population is not clear. Objective: The objective of the study was to determine whether DPP4 activity and active glucagon-like peptide-1 (GLP-1) were predictive of the onset of prediabetes and type 2 diabetes. Design, Setting, and Patients: This was a 4-year follow-up study conducted in Sichuan, China. A total of 474 Chinese women and men aged 18–70 years were studied. Main Outcome Measures: All subjects were divided into 3 groups (normal glucose tolerance, prediabetes, and type 2 diabetes) on the basis of their glucose metabolism status after 4 years. The DPP4 activity, active GLP-1, and glucagon were measured at baseline and 4 years later. Results: The baseline DPP4 activity was significantly higher in subjects who had progressed to prediabetes or type 2 diabetes compared with subjects who remained normoglycemic (P < .01). In a multiple linear regression analysis, baseline DPP4 activity and active GLP-1 were independent predictors of an increase in insulin resistance over a 4-year period (P < .05). Cox proportional hazards models revealed that DPP4 activity independently predicted the risk of developing prediabetes [relative risk 2.77 (95% confidence interval 1.38–5.55), P < .01] and type 2 diabetes [5.10 (95% confidence interval 1.48–17.61), P < .05] after adjustment for confounding risk factors. Conclusions: DPP4 activity is an important predictor of the onset of insulin resistance, prediabetes, and type 2 diabetes in apparently healthy Chinese individuals. This finding may have important implications for understanding the etiology of diabetes.

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Temporal Trends in Incident Hospitalization for Diabetes-Related Foot Ulcer in Type 2 Diabetes: The Fremantle Diabetes Study

10.2337/figshare.13377134 ◽

2021 ◽

Author(s):

Emma J Hamilton ◽

Wendy A Davis ◽

Ranita Siru ◽

Mendel Baba ◽

Paul E Norman ◽

...

Keyword(s):

Type 2 Diabetes ◽

Proportional Hazards ◽

Temporal Trends ◽

Age Groups ◽

Foot Ulcer ◽

Cox Proportional Hazards ◽

Diabetes Diagnosis ◽

Incident Rate

Objective: To determine whether, reflecting trends in other chronic complications, incident hospitalization for diabetes-related foot ulcer (DFU) has declined over recent decades in type 2 diabetes. Research design and methods: Participants with type 2 diabetes from the community-based Fremantle Diabetes Study Phases I (FDS1; 1,296 participants, mean age 64.0 years, 48.6% males, recruited 1993-1996) and II (FDS2; 1,509 participants, mean age 65.4 years, 51.8% males, recruited 2008-2011) were followed from entry to first hospitalization for/with DFU, death or 5 years (whichever came first). Incident rate ratios (IRRs) and incident rate differences (IRDs) were calculated for FDS2 versus FDS1 overall and in 10-year age-groups. Cox proportional hazards modelling determined independent predictors of first DFU hospitalization in the combined cohort. Results: Incident DFU hospitalization (95% CI) was 1.9 (0.9-3.3) /1,000 person-years in FDS1 during 5,879 person-years of follow-up, and 4.5 (3.0-6.4) /1,000 person-years in FDS2 during 6,915 person-years of follow-up. The crude IRR (95% CI) was 2.40 (1.17-5.28), P=0.013) and IRD 2.6 (0.7-4.5) /1,000 person-years (P=0.010). The highest incidence rate (IR) for any age-group was 23.6/1,000 person-years in FDS2 participants aged 31-40 years. Age at diabetes diagnosis (inverse), HbA1c, insulin use, height, ln(urinary albumin:creatinine), absence of any foot pulse, previous peripheral revascularization and peripheral sensory neuropathy (PSN) were independent predictors of incident hospitalization for/with DFU. Conclusions: Incident DFU hospitalizations complicating type 2 diabetes increased between FDS Phases, especially in younger participants, and were more likely in those with PSN, peripheral arterial disease and suboptimal glycemic control at baseline.

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Cluster Analysis of Cardiovascular Phenotypes in Patients With Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Potential Approach to Precision Medicine

10.2337/figshare.16722358.v1 ◽

2021 ◽

Author(s):

Abhinav Sharma ◽

Yinggan Zheng ◽

Justin A. Ezekowitz ◽

Cynthia M. Westerhout ◽

Jacob A. Udell ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cluster Analysis ◽

Proportional Hazards ◽

Cardiovascular Death ◽

Cox Proportional Hazards ◽

Machine Learning Algorithms ◽

Atherosclerotic Cardiovascular Disease ◽

Asian Patients

Objective: Phenotypic heterogeneity among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) is ill defined. We used cluster analysis machine learning algorithms to identify phenotypes among trial participants with T2DM and ASCVD. Research Design and Methods: We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n=14,671), a cardiovascular outcome safety trial comparing sitagliptin with placebo in patients with T2DM and ASCVD (median follow-up 3.0 years). Cluster analysis using 40 baseline variables was conducted, with associations between clusters and the primary composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina) assessed by Cox proportional hazards models. We replicated the results using the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial. Results: Four distinct phenotypes were identified: cluster I included Caucasian men with a high prevalence of coronary artery disease; cluster II included Asian patients with a low body mass index; cluster III included women with non-coronary ASCVD disease; and cluster IV included patients with heart failure and kidney dysfunction. The primary outcome occurred respectively in 11.6%, 8.6%, 10.3%, and 16.8% of patients in clusters I to IV. The crude difference in cardiovascular risk for the highest versus lowest risk cluster (cluster IV vs. II) was statistically significant (HR, 2.74; 95% CI, 2.29-3.29). Similar phenotypes and outcomes were identified in EXSCEL. Conclusions: In patients with T2DM and ASCVD, cluster analysis identified four clinically distinct groups. Further cardiovascular phenotyping is warranted to inform patient care and optimize clinical trial designs.

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