Lower Risk Of Type 2 Diabetes Mellitus Research Articles

Association between Diet Quality and Risk of Type 2 Diabetes Mellitus in Patients with Coronary Heart Disease: Findings from the CORDIOPREV Study.

The incidence of type 2 diabetes mellitus (T2DM) is growing in Western countries. Nutritional interventions that promote high-quality dietary patterns could help reverse this trend. We aimed to evaluate whether changes in Nutrient-Rich Food Index 9.3 (NRF9.3) were related to the risk of developing T2DM in patients with coronary heart disease (CHD). The study was carried out in the context of two healthy dietary interventions (a Mediterranean and a low-fat diet). For this purpose, we evaluated all the patients in the CORDIOPREV study without T2DM at baseline. Data were obtained during the first 5 years of dietary intervention. The score was calculated using the Food Frequency Questionnaires at baseline and after 1 year of intervention. After 5 years of follow-up, 106 patients developed T2DM (incident-T2DM), while 316 subjects did not (non-T2DM). Total NRF9.3 score and changes during the first year of intervention were compared between incident-T2DM and non-T2DM. Incident-T2DM showed less improvement in NRF9.3 than non-T2DM (p = 0.010). In the multi-adjusted Cox proportional hazard study, patients with greater improvement in NRF9.3 had over 50% less risk of developing T2DM compared with the lowest tertile (HR 2.10, 95%, CI = 1.12-3.56). In conclusion, improved diet quality in terms of nutrient density after the dietary intervention was associated with a lower risk of T2DM in patients with CHD.

Association between dietary antioxidant capacity and type 2 diabetes mellitus in Chinese adults: a population-based cross-sectional study

BackgroundHigher intakes of dietary antioxidants have been linked to a lower type 2 diabetes mellitus (T2DM) risk. However, few studies have comprehensively examined the overall dietary antioxidant capacity, assessed by dietary antioxidant quality scores (DAQS) and dietary total antioxidant capacity (DTAC), related to T2DM risk, especially in populations consuming relatively monotonous diets. This study aimed to evaluate the associations of DAQS, DTAC, and T2DM among rural Chinese adults.MethodsData from 12,467 participants from the Natural Population Cohort of Northwest China: Ningxia Project was analyzed. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. DAQS were calculated based on vitamins A, C, and E, zinc (Zn), and selenium (Se) intake. DTAC was estimated using the ferric-reducing ability of plasma assay. Logistic regression models were used to evaluate the associations of DAQS and DTAC with T2DM risk. Restricted cubic splines were used to assess potential non-linear relationships between DTAC and T2DM.ResultsT2DM was observed in 1,238 (9.9%) participants. After adjusting for confounders, compared to the lowest tertiles (T1) of DAQS, the odds ratios (ORs) for T2DM were 1.03 (95% CI 0.82–1.30) in T2 and 0.85 (95% CI 0.68–1.06) in T3 (P = 0.010). Compared to T1, the ORs for T2DM in the highest T3 were 0.78 (95% CI 0.67–0.91, P-trend = 0.008) for vitamin A, 1.34 (95% CI 1.15–1.56, P-trend < 0.001) for vitamin E, 0.83 (95% CI 0.71–0.97, P-trend = 0.007) for Se, and 0.86 (95% CI 0.74–1.01, P-trend = 0.033) for Zn. Compared to the lowest quartile(Q1) of DTAC, the OR in the highest Q4 was 0.96 (95% CI 0.80–1.17, P-trend = 0.024) for T2DM. A non-linear relationship was observed between DATC and T2DM.ConclusionHigher DAQS and DATC were associated with a lower T2DM risk, suggesting that consuming antioxidant-rich foods may reduce the T2DM risk.

Type 2 diabetes mellitus and the risk of male infertility: a Mendelian randomization study.

To assess the causal effect of type 2 diabetes mellitus (T2DM) on male infertility (MI) and erectile dysfunction (ED) by Mendelian randomization (MR) analysis. Data for T2DM, MI, and ED were obtained from genome-wide association studies (GWAS) involving 298, 957, 73, 479, and 223, 805 Europeans, respectively. We performed univariate MR analysis using MR Egger, Weighted median (WM) and Inverse variance weighted (IVW) methods to assess causal effects among the three. Through the Genotype Tissue Expression (GTEx) database, single-nucleotide polymorphisms (SNPs) that affect the expression levels of T2DM-related genes were located using expression quantitative trait loci (eQTL). MR analysis showed a significant causal relationship between T2DM and ED (WM, OR: 1.180, 95%CI: 1.010-1.378, P = 0.037; IVW, OR: 1.190, 95%CI: 1.084-1.300, P < 0.001). There is also a significant causal relationship between T2DM and MI (MR Egger, OR: 0.549, 95%CI: 0.317-0.952, P = 0.037; WM, OR: 0.593, 95%CI: 0.400, P = 0.010; IVW, OR: 0.767, 95%CI: 0.600-0.980, P = 0.034). ED may not cause MI (P > 0.05). We also found that rs6585827 corresponding to the PLEKHA1 gene associated with T2DM is an eQTL variant affecting the expression of this gene. T2DM has a direct causal effect on ED and MI. The level of PLEKHA1 expression suppressed by rs6585827 is potentially associated with a lower risk of T2DM.

Sleep Patterns, Plasma Metabolome, and Risk of Incident Type 2 Diabetes Mellitus.

A healthy sleep pattern has been related to a lower risk of type 2 diabetes mellitus (T2DM). We aimed to identify the metabolomic signature for the healthy sleep pattern and assess its potential causality with T2DM. This study included 78 659 participants with complete phenotypic data (sleep information and metabolomic measurements) from the UK Biobank study. Elastic net regularized regression was applied to calculate a metabolomic signature reflecting overall sleep patterns. We also performed genome-wide association analysis of the metabolomic signature and one-sample mendelian randomization (MR) with T2DM risk. During a median of 8.8 years of follow-up, we documented 1489 incident T2DM cases. Compared with individuals who had an unhealthy sleep pattern, those with a healthy sleep pattern had a 49% lower risk of T2DM (multivariable-adjusted hazard ratio [HR], 0.51; 95% CI, 0.40-0.63). We further constructed a metabolomic signature using elastic net regularized regressions that comprised 153 metabolites, and robustly correlated with sleep pattern (r = 0.19; P = 3×10-325). In multivariable Cox regressions, the metabolomic signature showed a statistically significant inverse association with T2DM risk (HR per SD increment in the signature, 0.56; 95% CI, 0.52-0.60). Additionally, MR analyses indicated a significant causal relation between the genetically predicted metabolomic signature and incident T2DM (P for trend < .001). In this large prospective study, we identified a metabolomic signature for the healthy sleep pattern, and such a signature showed a potential causality with T2DM risk independent of traditional risk factors.

NAFLD: A pretransplant and post-transplant conundrum.

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Abstract P630: Dietary Sodium Intake Increases the Risk of Developing Type 2 Diabetes Mellitus in the Million Veteran Program

Background: Type 2 Diabetes Mellitus (T2DM) affects 10.5% of the US population (~34.2 million people). While previous studies have shown that high intake of sodium is associated with the worsening of the T2DM parameters, it is unclear whether dietary sodium intake is associated with incidence of T2DM. We prospectively examined the association of sodium and potassium intake and risk for T2DM among participants of the Million Veteran Program (MVP). Methods: Between 2011 to 2020, 379,852 participants from the MVP completed a semi-quantitative food frequency questionnaire (sFFQ). Incidence of T2DM was ascertained using ICD-9 code 258.xx from electronic health records. We used Cox proportional hazards model to calculate hazard ratio (HR) with 95% confidence intervals (CIs) for T2DM adjusting for confounding factors. Results: Among the 234,721 veterans analyzed, mean age was 65 years (age range 19-106), 91% were male, and 88% were Caucasian. The observed energy-adjusted mean sodium intake was 1222 mg/day (1103 for females, 1234 for males) and potassium intake was 2596 mg/day (2534 for females, 2602 for males). During a mean follow-up of 4.4 years, 8,753 participants developed T2DM. After adjusting for confounding factors, a higher sodium intake was associated with 11% higher risk of T2DM (HR: 1.11, 95% CI: 1.04, 1.19, p-trend=0.0006); while a higher potassium intake was associated with a 6% lower risk of T2DM (HR: 0.94, 95% CI: 0.92, 0.97) (Figure). Conclusion: Higher intake of dietary sodium and lower intake of dietary potassium were each associated with a higher risk of developing T2DM among US veterans.

Association between a priori and a posteriori dietary patterns and the risk of type 2 diabetes: a representative cohort study in Taiwan.

The present study aimed to investigate the relationship between dietary patterns and the risk of type 2 diabetes mellitus (T2DM) among Taiwanese individuals. Data were collected using a nationwide cohort study (2001-15) from the Triple-High Database. Dietary intake was assessed using the twenty-group food frequency questionnaire and used to calculate alternate Mediterranean diet (aMED) and Dietary Approaches to Stop Hypertension (DASH) scores. Principal component analysis (PCA) and partial least-squares (PLS) regression were used to derive dietary patterns, with incident T2DM as the outcome. Multivariable-adjusted hazard ratios and 95 % confidence intervals were calculated using time-dependent Cox proportional hazards (Cox PH) regression analysis, and subgroup analyses were performed. A total of 4705 participants were enrolled in the study, and 995 had newly developed T2DM during the median 5⋅28-year follow-up period (30⋅7 per 1000 person-years). Six dietary patterns were extracted (PCA: Western, prudent, dairy and plant-based; PLS: health-conscious, fish-vegetable and fruit-seafood). The highest aMED score quartile had a 25 % (hazard ratio 0⋅75; 95 % CI 0⋅61, 0⋅92; P = 0⋅039) lower risk of T2DM than the lowest quartile. This association remained significant after adjustment (adjusted hazard ratio 0⋅74; 95 % CI 0⋅60, 0⋅91; P = 0⋅010), and no effect modifier was found for aMED. The DASH scores, PCA and PLS dietary patterns were not significant after adjustment. In conclusion, high adherence to a MED-type dietary pattern by Taiwanese foods was associated with a lower risk of T2DM in the Taiwanese population, regardless of unhealthy lifestyle habits.

BMI variability and incident diabetes mellitus, Tehran Lipid and Glucose Study (TLGS)

Previous epidemiologic studies debated the association of body mass index (BMI) trends with cardiovascular disease and mortality. This study aimed to evaluate the association of BMI variability and slope with the incidence of Type 2 diabetes mellitus (T2DM) in a sex-stratified 15.8-year follow-up in the population-based Tehran Lipid and Glucose Study (TLGS). Of 10,911 individuals aged 20–60 years, 4981 subjects were included and followed for 15.8-years. The slope coefficient of BMI in the linear regression model represented individuals’ BMI trends up to the incidence of DM. The root mean squared error (RMSE) of the BMI linear trend was selected to reflect BMI variability through six follow-ups. Cox proportional hazards regression was used to investigate the association of the baseline BMI, BMI slope and RMSE with the incidence of T2DM among men and women. Multivariable-adjusted HRs of T2DM for each SD increment in BMI slope was 1.18 (95% CI: 0.94–1.48, p = 0.161) in normal weight men and 1.26 (95% CI: 1.10–1.44, p = 0.001) in overweight and obese men. However, in women, each SD increment in BMI slope increased the risk of T2DM with a HR of 1.19 (95% CI: 1.01–1.40, p = 0.039) in normal weight, and 1.14 (95% CI: 1.08–1.19, p < 0.001) in women with BMI ≥ 25 kg/m2. In men with a baseline BMI ≥ 25 kg/m2, BMI-RMSE was associated with a decreased risk of T2DM (HR: 0.71, 95% CI: 0.53–0.93, p = 0.015). Baseline BMI was not associated with the risk of diabetes in men and women. Positive BMI slope is associated with the development of diabetes in both sexes. The association of BMI variability with incident T2DM differs according to sex and baseline BMI. BMI variability is associated with a lower risk of T2DM in overweight and obese men. BMI variability in women and baseline BMI in both gender are not related to the risk of T2DM.

Plasma level of ATPase inhibitory factor 1 (IF1) is associated with type 2 diabetes risk in humans: A prospective cohort study

AimMitochondrial dysfunction is associated with the development of type 2 diabetes mellitus (T2DM). It is thus of clinical relevance to identify plasma biomarkers of mitochondrial dysfunction associated with the risk of T2DM.ATPase inhibitory factor 1 (IF1) endogenously inhibits mitochondrial ATP synthase activity. Here, we analyzed association of the plasma IF1 level with markers of glucose homeostasis and with the conversion to new-onset diabetes (NOD) in individuals with prediabetes. MethodsIn the IT-DIAB prospective study, the baseline plasma level of IF1 was measured in 307 participants with prediabetes. The primary outcome was the incidence of NOD within five years of follow-up. Cross-sectional analysis of the IF1 level was also done in two independent interventional studies. Correlations between plasma IF1 and metabolic parameters at baseline were assessed by Spearman's correlation coefficients, and the association with the risk of NOD was determined using Cox proportional‐hazards models. ResultsIn IT-DIAB, the mean IF1 plasma level was lower in participants who developed NOD than in those who did not (537 ± 248 versus 621 ± 313 ng/mL, P = 0.01). The plasma IF1 level negatively correlated with clinical variables associated with obesity and insulin resistance, including the body mass index (r = −0.20, P = 0.0005) and homeostasis model assessment of insulin resistance (HOMA-IR). (r = −0.37, P < 0.0001). Conversely, IF1 was positively associated with plasma markers of cardiometabolic health, such as HDL-C (r = 0.63, P < 0.0001) and apoA-I (r = 0.33, P < 0.0001). These correlations were confirmed in cross-sectional analyses. In IT-DIAB, the IF1 level was significantly associated with a lower risk of T2DM after adjustment for age, sex, and fasting plasma glucose (HR [95% CI] per 1 SD = 0.76 [0.62; 0.94], P = 0.012). ConclusionWe identified for the first time the mitochondrial-related biomarker IF1 as being associated with the risk of T2DM.

Prospective study of breakfast frequency and timing and the risk of incident type 2 diabetes in community-dwelling older adults: the Cardiovascular Health Study

No evidence-based recommendations regarding optimal breakfast frequency and timing and type 2 diabetes mellitus (T2DM) exist for older adults because of limited studies. We sought to prospectively assess relations between breakfast frequency and timing and T2DM risk among older adults and determine whether these depended on sex or cardiometabolic risk factors. Weekly breakfast frequency and usual daily breakfast time were assessed by questionnaire at baseline in 3747 older adults (aged≥65 y) from the Cardiovascular Health Study (CHS) who were free of cancer and T2DM and followed for 17.6 y. Multivariable-adjusted hazard ratios (aHRs) with 95% CIs estimated from Cox proportional hazards models were used to quantify associations with T2DM. Most CHS participants (median age: 74 y; IQR: 71-78 y) consumed breakfast daily (85.5%), and 73% had their first daily eating occasion between 07:00 and 09:00, both of which were associated with higher socioeconomic status, factors that are indicative of a healthier lifestyle, and lower levels of cardiometabolic risk indicators at baseline. During follow-up, 547 T2DM cases were documented. No strong evidence was observed linking breakfast frequency and risk of T2DM. Compared with participants whose breakfast timing (first eating occasion of the day) was 07:00-09:00, those who broke fast after 09:00 had an aHR for T2DM of 0.71 (95% CI: 0.51, 0.99). This association was present in participants with impaired fasting glucose at baseline (aHR: 0.61; 95% CI: 0.39, 0.95) but not in those without (aHR: 0.83; 95% CI: 0.50, 1.38). No associations between eating frequency or timing and T2DM were observed within other prespecified subgroups. Eating breakfast daily was not associated with either higher or lower risk of T2DM in this cohort of older adults, whereas a later (after 09:00) daily first eating occasion time was associated with lower T2DM risk in participants with impaired fasting glucose at baseline.This trial was registered at clinicaltrials.gov as NCT00005133.

Magnesium Supplementation Is Associated with a Lower Cardio-Metabolic Risk in Patients Submitted to Bariatric Surgery.

Literature has demonstrated an inverse relation between magnesium (Mg) consumption and development of type 2 diabetes mellitus (T2DM), hypertension (HT), and dyslipidemia. After bariatric surgery (BS), micronutrients deficiencies are common, it being important to ensure appropriate supplementation. There is no recommendation about Mg supplementation and to our knowledge, its effect has not been studied to date. Our aim was to evaluate the effect of Mg supplementation in cardio-metabolic risk factors on post-bariatric patients. A retrospective observational study of patients with obesity who underwent BS was performed. Data was assessed preoperatively and yearly (4-year follow-up). A total of 3363 patients were included. In the first year of follow-up, 79.8% (n = 2123) of the patients were supplemented with Mg, with evidence of slightly decreased percentages in the following years. Mg deficiency (serum Mg < 1.52mEq/L) was more common among patients who were not supplemented during each year of follow-up (p < 0.05). Among those who underwent Mg supplementation, the percentage of T2DM, HT, or low-density lipoprotein cholesterol (LDL-C) > 130mg/dL was significantly lower. In the first year post-surgery, the supplementation group had a lower risk of T2DM (OR = 0.545, p < 0.0001), LDL-C > 130mg/dL (OR = 0.612, p < 0.0001), and HT (OR = 0.584, p < 0.0001). The OR for having these metabolic comorbidities persisted lower during the 4years' follow-up. Patients who had Mg deficiency had higher prevalence of T2DM and HT. Mg supplementation seems to have a protective effect on the development of T2DM, HT, and LDL-C > 130mg/dL in post-bariatric patients.

Genetic Variation in Targets of Antidiabetic Drugs and Alzheimer Disease Risk: A Mendelian Randomization Study.

Background and ObjectivesPrevious studies have highlighted antidiabetic drugs as repurposing candidates for Alzheimer disease (AD), but the disease-modifying effects are still unclear.MethodsA 2-sample mendelian randomization study design was applied to examine the association between genetic variation in the targets of 4 antidiabetic drug classes and AD risk. Genetic summary statistics for blood glucose were analyzed using UK Biobank data of 326,885 participants, whereas summary statistics for AD were retrieved from previous genome-wide association studies comprising 24,087 clinically diagnosed AD cases and 55,058 controls. Positive control analysis on type 2 diabetes mellitus (T2DM), insulin secretion, insulin resistance, and obesity-related traits was conducted to validate the selection of instrumental variables.ResultsIn the positive control analysis, genetic variation in sulfonylurea targets was associated with higher insulin secretion, a lower risk of T2DM, and an increment in body mass index, waist circumference, and hip circumference, consistent with drug mechanistic actions and previous trial evidence. In the primary analysis, genetic variation in sulfonylurea targets was associated with a lower risk of AD (odds ratio [OR] = 0.38 per 1 mmol/L decrement in blood glucose, 95% CI 0.19–0.72, p = 0.0034). These results for sulfonylureas were largely unchanged in the sensitivity analysis using a genetic variant, rs757110, that has been validated to modulate the target proteins of sulfonylureas (OR = 0.35 per 1 mmol/L decrement in blood glucose, 95% CI 0.15–0.82, p = 0.016). An association between genetic variations in the glucagon-like peptide 1 (GLP-1) analogue target and a lower risk of AD was also observed (OR = 0.32 per 1 mmol/L decrement in blood glucose, 95% CI 0.13–0.79, p = 0.014). However, this result should be interpreted with caution because the positive control analyses for GLP-1 analogues did not comply with a weight-loss effect as shown in previous clinical trials. Results regarding other drug classes were inconclusive.DiscussionGenetic variation in sulfonylurea targets was associated with a lower risk of AD, and future studies are warranted to clarify the underlying mechanistic pathways between sulfonylureas and AD.

Higher intakes of nutrients are linked with a lower risk of cardiovascular diseases, type 2 diabetes mellitus, arthritis, and depression among Korean adults

Persons with underlying noncommunicable diseases (NCDs) are more likely to acquire severe coronavirus disease 2019 disease and to die from coronavirus disease 2019. An urgent need for potential therapy to prevent and control NCDs is critical. We hypothesized that higher intakes of multiple individual nutrients, fruits, or vegetables would be linked with a low risk of NCDs in the Korean population. Thus, we aim to explore the association between NCDs, including cardiovascular diseases, type 2 diabetes mellitus (T2DM), arthritis, depression, and dietary factors. A total of 56,462 adults aged 18 years (2009-2019) were included. Dietary factors, including intakes of multiple individual nutrients, fruits, and vegetables, were assessed. Multivariable-adjusted logistic regression models were used to explore the associations between dietary factors and NCDs. Interactions were found between intakes of multiple individual nutrients and sex for T2DM, hypertension, stroke, myocardial infarction, arthritis, and osteoarthritis. Only in women was a 2-fold increase in daily multiple individual nutrient intake (vitamins A, B1, B2, B3, C; potassium, protein; phosphorus; calcium; iron; monounsaturated fatty acid and polyunsaturated fatty acid; n-3 fatty acid and n-6 fatty acid; and water) associated with a lower prevalence of T2DM, hypertension, stroke, myocardial infarction, arthritis, and osteoarthritis. In both women and men, high fruit or vegetable consumption was linked with a lower risk of T2DM, hypertension, dyslipidemia, osteoarthritis, and depression than low consumption. Our findings found higher intakes of fruits, vegetables, and multiple individual nutrients are linked with a lower risk of NCDs in the Korean adult population. Further work is needed to identify whether interactions between intake of multiple individual nutrients, vegetables, and fruits affect the presence of NCDs.

Association of healthy lifestyle including a healthy sleep pattern with incident type 2 diabetes mellitus among individuals with hypertension

BackgroundEvidence is limited regarding the association of healthy lifestyle including sleep pattern with the risk of complicated type 2 diabetes mellitus (T2DM) among patients with hypertension. We aimed to investigate the associations of an overall healthy lifestyle including a healthy sleep pattern with subsequent development of T2DM among participants with hypertension compared to normotension, and to estimate how much of that risk could be prevented.MethodsThis study examined six lifestyle factors with T2DM cases among hypertension (227,966) and normotension (203,005) and their interaction in the UK Biobank. Low-risk lifestyle factors were defined as standard body mass index (BMI), drinking alcohol in moderation, nonsmoking, engaging in moderate- to vigorous-intensity physical activity, eating a high-quality diet, and maintaining a healthy sleep pattern.ResultsThere were 12,403 incident T2DM cases during an average of 8.63 years of follow-up. Compared to those with 0 low-risk lifestyle factors, HRs for those with 5–6 were 0.14 (95% CI 0.10 to 0.19) for hypertensive participants, 0.13 (95% CI 0.08 to 0.19) for normotensive participants, respectively (ptrend < 0.001). 76.93% of hypertensive participants were considerably less likely to develop T2DM if they adhered to five healthy lifestyle practices, increased to 81.14% if they followed 6-factors (with a healthy sleep pattern). Compared with hypertension adults, normotensive people gain more benefits if they stick to six healthy lifestyles [Population attributable risk (PAR%) 83.66%, 95% CI 79.45 to 87.00%, p for interaction = 0.0011].ConclusionsAdherence to a healthy lifestyle pattern including a healthy sleep pattern is associated with lower risk of T2DM in hypertensives, and this benefit is even further in normotensives.

The association between gender-related characteristics and type 2 diabetes risk in a multi-ethnic population: The HELIUS study

Background and aimsMen and women have different type 2 diabetes mellitus (T2DM) risks, which have been reported across populations of different ethnicity. Where differences in T2DM risk for sex (biological) have been studied, research on gender (socio-cultural) and T2DM risk is lacking. We explored, in a multi-ethnic population, the association of six gender-related characteristics with incident T2DM over 3 years, and the mediation by known risk factors for T2DM. Methods and resultsWe included 9605 women and 7080 men of the multi-ethnic HELIUS study (Amsterdam, the Netherlands). We studied associations between gender-related characteristics and incident T2DM, using Cox regression. After a median of 3.0 years (IQR 2.0; 4.0), 198 (2.1%) women and 137 (1.9%) men developed T2DM. A lower T2DM risk was observed in those not being the primary earner (HR 0.67; 95% CI 0.47; 0.93) and a higher desired level of social support (HR 0.62; 95% CI 0.44; 0.87). Hours spent on household work, home repairs, type of employment and male- or female-dominated occupation were not associated with T2DM incidence. No evidence for effect modification by biological sex or ethnicity was found. Known risk factors of T2DM did not mediate the observed associations. ConclusionGender-related characteristics, not being the primary earner and a higher desired social support were associated with reduced T2DM risk, and this was not mediated by known risk factors for T2DM.

Dietary Intake of Linoleic Acid, Its Concentrations, and the Risk of Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies.

Earlier evidence on the association between dietary polyunsaturated fatty acids and risk of diabetes has been conflicting. To quantitatively summarize previous studies on the association between dietary LA intake, its biomarkers, and the risk of type 2 diabetes mellitus (T2DM) in the general population. Our data sources included PubMed/MEDLINE, Scopus, and ISI Web of Science until 24 October 2020; reference lists of all related articles; and key journals. We included prospective cohort studies that examined the associations of linoleic acid (LA) with the risk of T2DM in adults. The inverse variance method was applied to calculate summary relative risk (RR) of LA intake and its biomarkers, and dose-response associations were modeled using restricted cubic splines. Twenty-three publications, covering a total of 31 prospective cohorts, were included; these studies included 297,685 participants (22,639 incident diabetes cases) with dietary intake assessment and 84,171 participants (18,458 incident diabetes cases) with biomarker measurements. High intake of LA was associated with a 6% lower risk of T2DM (summary relative risk [RR] 0.94, 95% CI 0.90, 0.99; I 2 = 48.5%). In the dose-response analysis, each 5% increment in energy from LA intake was associated with a 10% lower risk of T2DM. There was also evidence of a linear association between LA intake and diabetes, with the lowest risk at highest intakes. The summary RR for diabetes per SD increment in LA concentrations in adipose tissue/blood compartments was 0.85 (95% CI 0.80, 0.90; I2 = 66.2%). The certainty of the evidence was assessed as moderate. A limitation of our work was the observational design of studies included in the analyses. We found that a high intake of dietary LA and elevated concentrations of LA in the body were both significantly associated with a lower risk of T2DM. These findings support dietary recommendations to consume dietary LA.

High lipoprotein(a) concentrations are associated with lower type 2 diabetes risk in the Chinese Han population: a large retrospective cohort study

BackgroundLipoprotein (a) [Lp(a)] is a proven independent risk factor for coronary heart disease. It is also associated with type 2 diabetes mellitus (T2DM). However, the correlation between Lp(a) and T2DM has not been clearly elucidated.MethodsThis was a retrospective cohort study involving 9248 T2DM patients and 18,496 control individuals (1:2 matched). Patients were randomly selected from among inpatients in the Second Affiliated Hospital of Nanchang University between 2006 and 2017. Clinical characteristics were compared between the two groups. Spearman rank-order correlation coefficients were used to evaluate the strength and direction of monotonic associations of serum Lp(a) with other metabolic risk factors. Binary logistic regression analysis was used to establish the correlation between Lp(a) levels and T2DM risk.ResultsThe median Lp(a) concentration was lower in T2DM patients than in controls (16.42 vs. 16.88 mg/dL). Based on four quartiles of Lp(a) levels, there was a decrease in T2DM risk from 33.7% (Q1) to 31.96% (Q4) (P for trend < 0.0001). Then, Lp(a) levels > 28.72 mg/dL (Q4) were associated with a significantly lower T2DM risk in the unadjusted model [0.924 (0.861, 0.992), P = 0.030]. Similar results were obtained in adjusted models 1 [Q4, 0.925 (0.862, 0.993), P = 0.031] and 2 [Q4, 0.919 (0.854, 0.990), P = 0.026]. Furthermore, in the stratified analysis, Q4 of Lp(a) was associated with a significantly lower T2DM risk among men [0.813 (0.734, 0.900), P < 0.001] and those age > 60 years [0.819 (0.737, 0.910), P < 0.001]. In contrast, the low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) did not impact these correlations between Lp(a) and diabetes.ConclusionsThere is an inverse association between Lp(a) levels and T2DM risk in the Chinese population. Male patients, especially those aged more than 60 years with Lp(a) > 28.72 mg/dL, are low-risk T2DM individuals, regardless of LDL-C levels and CHD status.

1005-P: Patients with Overweight and Obesity at High-Risk for Type 2 Diabetes: A Predictive Model

Obesity is the most common chronic disease in the U.S. Patients with obesity are at high risk for type 2 diabetes mellitus (T2DM); however, many of their risk factors for T2DM are modifiable. It is important to identify patients with obesity at high risk for T2DM to appropriately direct treatment and resources. We conducted an observational study of EMR data of 399,711 adults with BMI ≥ 25 kg/m2 and without baseline T2DM between 2000 and 2019. We first identified a literature-based pool of risk factors for T2DM onset and conducted variable selection by applying LASSO penalized Cox regression with ten-fold cross-validation on an 80% training dataset. We estimated a regular Cox model on the training dataset with selected variables and evaluated model performance on the remaining 20% dataset. Over a mean of 7.4 years of follow-up, 38,898 (9.8%) study patients developed T2DM. The predictive model achieved a Harrell’s C-statistic of 0.81. The greatest risk of T2DM was associated with gestational diabetes (HR 2.53; 95% CI 2.12-3.01), Asian and Hispanic race/ethnicity (HRs 2.38 and 1.94; 95% CIs 2.24-2.53 and 1.86-2.02, respectively), family history of DM (HR 2.00; 95% CI 1.95-2.04) and PCOS (HR 1.84; 95% CI 1.63-2.07). Female sex (HR 0.77; 95% CI 0.75-0.79), having a partner (HR 0.90; 95% CI 0.88-0.92) or commercial insurance (HR 0.86; 95% CI 0.84-0.88) were associated with a lower risk of T2DM. Characteristics found in &amp;gt;5% of patients that carried additional risk included proteinuria (5.0% of patients; HR 1.53; 95% CI 1.47-1.59), hypertension (23.9%; HR 1.21; 95% CI 1.18-1.25), high cholesterol (11.9%; HR 1.19; 95% CI 1.15-1.23), and history of smoking (40.5%; HR 1.18; 95% CI 1.15-1.21). Each standard deviation increase in BMI (5.2 kg/m2) was associated with a 1.51-fold (95% CI 1.49-1.52) increase in T2DM onset. It is feasible to use predictive modeling to identify patients with overweight and obesity at high risk of T2DM. This approach could be utilized to guide population management and clinical treatment decisions. Disclosure A. Turchin: Consultant; Self; Proteomics International, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Sanofi, Stock/Shareholder; Self; Brio Systems. F. J. Morrison: None. M. Shubina: None. S. Shinde: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. N. Ahmad: Employee; Self; Eli Lilly and Company. H. Kan: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Bristol-Myers Squibb Company, GlaxoSmithKline plc. Funding Eli Lilly and Company

The association of energy and macronutrient intake at dinner vs breakfast with the incidence of type 2 diabetes mellitus in a cohort study: The China Health and Nutrition Survey, 1997-2011.

This study aims to investigate the association of energy and macronutrient intake at dinner vs breakfast with the incidence of type 2 diabetes mellitus (T2DM). A total of 11 153 adults, including 811 with T2DM, completed a questionnaire about energy and macronutrient intake in the China Health and Nutrition Survey (1997-2011). The differences (Δ) in energy and macronutrient intake between dinner and breakfast (Δ=dinner- breakfast) were categorized into quintiles. Cox proportional hazards regression models were performed to explore the association between Δ and the risk of T2DM and to investigate the change of the risk when 5% total energy or energy provided by macronutrients at dinner was substituted with total energy or energy provided by macronutrients at breakfast by isocaloric substitution models. After adjustment for potential confounders, compared with participants in the lowest quintile, participants in the highest quintile were more likely to develop T2DM (hazard ratio [HR]Δenergy 1.46, 95% CI 1.13-1.87; HRΔfat 1.85, 95% CI 1.43-2.41; HRΔprotein 1.37, 95% CI 1.06-1.78). Isocalorically replacing 5% energy at dinner with energy at breakfast was associated with a 7% lower T2DM risk. Replacing 5% energy provided by fat at dinner with energy provided by carbohydrate, protein, and fat at breakfast was associated with a 9%, 5%, and 7% lower T2DM risk, respectively. Replacing 5% energy provided by protein at dinner with energy provided by carbohydrate or protein at breakfast was associated with a 5% lower T2DM risk. Higher intake of energy, protein, and fat at dinner than at breakfast increased the risk of T2DM.

Loss of Znt8 function in diabetes mellitus: risk or benefit?

The zinc transporter 8 (ZnT8) plays an essential role in zinc homeostasis inside pancreatic β cells, its function is related to the stabilization of insulin hexameric form. Genome-wide association studies (GWAS) have established a positive and negative relationship of ZnT8 variants with type 2 diabetes mellitus (T2DM), exposing a dual and controversial role. The first hypotheses about its role in T2DM indicated a higher risk of developing T2DM for loss of function; nevertheless, recent GWAS of ZnT8 loss-of-function mutations in humans have shown protection against T2DM. With regard to the ZnT8 role in T2DM, most studies have focused on rodent models and common high-risk variants; however, considerable differences between human and rodent models have been found and the new approaches have included lower-frequency variants as a tool to clarify gene functions, allowing a better understanding of the disease and offering possible therapeutic targets. Therefore, this review will discuss the physiological effects of the ZnT8 variants associated with a major and lower risk of T2DM, emphasizing the low- and rare-frequency variants.