Incident Type 2 Diabetes Mellitus Cases Research Articles

Accelerated biological aging, mediating amino acids, and risk of incident type 2 diabetes: a prospective cohort study.

Aging plays an important role in type 2 diabetes mellitus (T2DM). But the association between accelerated biological age and T2DM, and the mechanisms underlying this association remains unclear. Thus, this study aimed to examine the associations of biological aging with T2DM, and explore the potential mediation effect of amino acids. This prospective cohort study included 95,773 participants in the UK Biobank who were free of diabetes at baseline. Biological age was measured from clinical traits using PhenoAgeAccel. Cox proportional hazard models were used to estimate the hazard ritios (HRs) and 95% confidence intervals (CIs), and mediation analysis was used to explore the mediation effect of amino acids. During a median follow-up of 14.02 years, 6,347 incident T2DM cases were recorded. After multivariable adjustment for sociodemographic characteristics, lifestyle factors, and other risk factors of T2DM, participants with older biological age were at increased risk of incident T2DM (30% increase per standard deviation of PhenoAgeAccel, 95% CI: 28.0-33.0%). Additionally, higher branched chain amino acids (BCAAs) including isoleucine and leucine, aromatic amino acids (AAAs) including phenylalanine and tyrosine, were associated with increased PhenoAgeAccel and risk of incident T2DM; while glutamine and glycine were inversely associated. Alanine, glutamine, glycine, phenylalanine, tyrosine, isoleucine, leucine, and total concentration of branched-chain amnio acids could partially explain the associations between PhenoAgeAccel and T2DM. Accelerated biological aging was associated with increased risk of incident T2DM independent of chronological age and may be a risk factor of T2DM, partially mediated by several amino acids.

Trajectories of social isolation and loneliness and the risk of incident type 2 diabetes mellitus across genetic risk score

AimThis study aimed to investigate the association of social isolation, loneliness, and their trajectory with the risk of developing type 2 diabetes mellitus (T2DM) across genetic risk. MethodsWe included 439,337 participants (mean age 56.3 ± 8.1 years) enrolled in the UK Biobank study who were followed up until May 31, 2021. Social isolation and loneliness were self-reported and were further categorized into never, transient, incident, and persistent patterns. ResultsDuring a median follow-up of 12.7 years, 15,258 incident T2DM cases were documented. Social isolation (versus no social isolation: hazard ratio (HR) 95 % confidence interval (CI) 1.04 [1.00;1.09]) and loneliness (versus no loneliness: 1.26 [1.19;1.34]) were associated with an increased T2DM risk, independent of the genetic risk for T2DM. The interactions existed between social isolation and loneliness (Pinteraction < 0.05); the increased T2DM risk associated with social isolation was only significant among participants without loneliness. In the longitudinal analysis, only persistent social isolation (versus never social isolation: 1.22 [1.02;1.45]) was associated with an increased T2DM risk, whereas incident loneliness (versus never loneliness: 1.95 [1.40;2.71]) and persistent loneliness (2.00 [1.31;3.04]) were associated with higher T2DM risks. ConclusionSocial isolation and loneliness, especially their persistent pattern, were independently associated with an increased incident T2DM risk, irrespective of an individual's genetic risk. Loneliness modified the association between social isolation and incident T2DM.

Social isolation, loneliness, and the risk of incident type 2 diabetes mellitus by glycemic status

AimThe modifying effect of prediabetic status on the association of social isolation and loneliness with the risk of type 2 diabetes mellitus (T2DM) remains uncertain. We aimed to explore whether prediabetic status modifies the association of social isolation and loneliness with incident T2DM. Methods358,951 participants with random blood glucose < 11.1 mmol/l, hemoglobin A1c < 6.5 % and without diagnosis of diabetes from the UK Biobank were included. Prediabetes was defined by hemoglobin A1c level at 5.7–6.4 %. Social isolation and loneliness were assessed using self-reported questionnaires. The study outcome was incident T2DM. ResultsDuring a median follow-up of 12.5 years, 13,213 (3.7 %) incident T2DM cases were documented. Social isolation and loneliness in subjects with normoglycemia (adjusted HR [95 %CI]: social isolation: 1.14 [1.07;1.23]; loneliness: 1.33 [1.20;1.47]) were more strongly associated with increased risk of T2DM than in those with prediabetes (adjusted HR [95 %CI]: social isolation: 0.97 [0.91;1.03]; loneliness: 1.04 [0.95;1.13]) (Both P for interaction < 0.001). Among individuals with prediabetes, alcoholic consumption (30.9 %), household income (23.3 %), healthy sleep (17.1 %), loneliness (14.9 %), and physical activity (12.6 %) mediated most of the variance in the association between social isolation and incident T2DM, while body mass index (17.9 %) and healthy sleep (17.6 %) mediated most of the variance in the association between loneliness and incident T2DM. ConclusionSocial isolation and loneliness were independently associated with a higher risk of T2DM among individuals without prediabetes. Among those with prediabetes, the association of social isolation and loneliness with incident T2DM were mainly mediated by some socioeconomic and lifestyle factors.

Influence of neighborhood-level socioeconomic deprivation and individual socioeconomic position on risk of developing type 2 diabetes in older men: a longitudinal analysis in the British Regional Heart Study cohort

IntroductionEvidence from longitudinal studies on the influence of neighborhood socioeconomic deprivation in older age on the development of type 2 diabetes mellitus (T2DM) is limited. This study investigates the prospective...

Association Between Incident Type 2 Diabetes and Opium Use: Mediation by Body Mass and Adiposity.

Opiates can affect glucose metabolism and obesity, but no large prospective study (to our knowledge) has investigated the association between long-term opium use, body mass index (BMI; weight (kg)/height (m)2), and incident type 2 diabetes mellitus (T2DM). We analyzed prospective data from 50,045 Golestan Cohort Study participants in Iran (enrollment: 2004-2008). After excluding participants with preexisting diseases, including diabetes, we used adjusted Poisson regression models to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for T2DM in opium users compared with nonusers, using mediation analysis to assess the BMI-mediated association of opium use with incident T2DM. Of 40,083 included participants (mean age = 51.4 (standard deviation, 8.8) years; 56% female), 16% were opium users (median duration of use, 10 (interquartile range), 4-20) years). During follow-up (until January 2020), 5,342 incident T2DM cases were recorded, including 8.5% of opium users and 14.2% of nonusers. Opium use was associated with an overall decrease in incident T2DM (IRR=0.83, 95% CI: 0.75, 0.92), with a significant dose-response association. Most (84.3%) of this association was mediated by low BMI or waist circumference, and opium use did not have a direct association with incident T2DM (IRR=0.97, 95% CI: 0.87, 1.08). Long-term opium use was associated with lower incidence of T2DM, which was mediated by low body mass and adiposity.

Influences of resolvin D1 and D2 on the risk of type 2 diabetes mellitus: a Chinese community-based cohort study.

Although cellular and animal studies have reported that resolvin D1 (RvD1) and resolvin D2 (RvD2) are mechanisms involved in the development of type 2 diabetes mellitus (T2DM), the impact of RvD1 and RvD2 on the risk of T2DM at a population level remains unclear. We included 2755 non-diabetic adults from a community-based cohort in China and followed them for seven years. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of RvD1 and RvD2 with T2DM probability. Time-dependent receiver operator characteristics (ROC) curve was used to evaluate the predictive performance of RvD1 and RvD2 for the risk of T2DM based on the Chinese CDC T2DM prediction model (CDRS). A total of 172 incident T2DM cases were identified. Multivariate-adjusted HRs (95% CI) for T2DM across quartiles of RvD1 levels (Q1, Q2, Q3 and Q4) were 1.00, 1.64 (1.03-2.63), 1.80 (1.13-2.86) and 1.61 (1.01-2.57), respectively. Additionally, body mass index (BMI) showed a significant effect modification in the association of RvD1 with incident T2DM (P interaction = 0.026). After multivariate adjustment, the HR (95% CI) for T2DM in the fourth compared with the first quartile of RvD2 was 1.94 (95% CI: 1.24-3.03). Time-dependent ROC analysis showed that the area under time-dependent ROC curves of the "CDRS+RvD1+RvD2" model for the 3-, 5- and 7-year risk of T2DM were 0.842, 0.835 and 0.828, respectively. Higher RvD1 and RvD2 levels are associated with a higher risk of T2DM at the population level.

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.

Association between polychlorinated biphenyls exposure and incident type 2 diabetes mellitus: A nested case-control study

BackgroundPrevious epidemiological studies indicated that the association between polychlorinated biphenyls (PCB) and type 2 diabetes mellitus (T2DM) was inconclusive. ObjectiveWe investigated the association between PCBs exposure and incident T2DM in a nested case-control study, and further explored the relationship between PCBs and 5-year fasting blood glucose (FBG) changes. MethodsBaseline concentrations of seven indicator-PCB (PCB-28, 52, 101, 118, 138, 153, 180) were measured in 1006 pairs of incident T2DM cases and matched controls nested within the Dongfeng-Tongji cohort. Conditional logistic regression models and pre-adjusted residuals method were used to assess the associations between PCBs and incident T2DM. We further computed beta coefficients (βs) of 5-year FBG changes using multivariable generalized linear regression. ResultsNon-dioxin-like PCBs (NDL-PCBs) were significantly associated with higher T2DM incidence after adjustment for all covariates. Significant differences were observed for extreme quartiles comparisons (Q4 vs. Q1) of PCBs except PCB-138, and the incidence of T2DM were 1- to 3-fold higher among those in the highest versus lowest PCBs quartiles. Serum NDL-PCBs were positively associated with changes in FBG (P for overall association ≤0.01). Additionally, triglycerides mediated the associations between PCBs and T2DM incidence. ConclusionOur findings showed positive associations of NDL-PCBs with incident T2DM and 5-year FBG changes. PCBs increased incident T2DM via lipid metabolic pathways.

Outdoor light at night, genetic predisposition and type 2 diabetes mellitus: A prospective cohort study

BackgroundAccording to animal and human epidemiologic studies, exposure to outdoor light at night (LAN) may cause circadian disruption, which may disturb sleep quality and lead to incident type 2 diabetes mellitus (T2DM). MethodsWe followed 283,374 persons from 2006 through 2020. Outdoor LAN exposure was estimated using satellite data for individual address with 500 m2 scale buffer during follow-up. Incidence of T2DM was confirmed by hospital inpatient records. We identified potential confounders by a directed acyclic graph, including demographic, genetic, individual and regional level socioeconomic status, and environmental risk factors, and calculated hazard ratios (HRs) and 95% confidence intervals (CIs) through time-varying Cox proportional hazard model. Furthermore, we examined the association of outdoor LAN with a defined health sleep scores and moderation of genetic predisposition and shift work on the relationship of outdoor LAN and incident T2DM. ResultsWe identified 7,775 incident T2DM cases over 3,027,505 person-years. Higher outdoor LAN exposures were significantly associated with higher risk of T2DM. The estimated HR for incident T2DM with an interquartile range (IQR: 11.22 nW/cm2/sr) increase in outdoor LAN was 1.05 (95%CI: 1.01, 1.09) in the fully adjusted model. Participants who lived in the highest quarter of outdoor LAN area were more likely to develop T2DM (HR: 1.14,95%CI: 1.02, 1.27). Besides, those who were exposed to higher levels of outdoor LAN had poorer sleep quality. No moderation role of PRS on outdoor LAN-induced T2DM observed both on the multiplicated and additive scale. The hazards of outdoor LAN were observed in those who never owned a night shift work. ConclusionAlthough further work is required to clarify potential mechanisms, our findings indicate that exposure to residential outdoor LAN may contribute to T2DM risk and low sleep quality.

Association between Non-Steroidal Anti-Inflammatory Drugs Use and the Risk of Type 2 Diabetes Mellitus: A Nationwide Retrospective Cohort Study

Background: Although the link between non-steroidal anti-inflammatory drugs (NSAIDs) and tramadol and symptomatic hypoglycemia has been documented, there is a limited understanding of the associations of NSAIDs and tramadol with the risk of type 2 diabetes mellitus (T2DM). This study was established to evaluate the association between the clinical use of NSAIDs and the risk of T2DM. Patients and methods: A historical cohort study was conducted using the National Health Insurance Research Database in Taiwan dated from 2000 to 2013. Patients who received NSAIDs for at least 3 prescription orders and without co-treatment of tramadol in the exposure period (from 2000 to 2005) were considered as the exposed cohort (n = 3047). In comparison, patients who received tramadol for at least 3 prescription orders and without concomitant use of NSAIDs in the exposure period were considered as the comparison cohort (n = 9141). The primary outcome was the occurrence of T2DM. Multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) derived from the Cox proportional hazard models were applied to determine the association between NSAIDs use and the risk of T2DM. Results: In the average follow-up period of 9.56 years, there were 159 newly diagnosed T2DM, with an incidence rate of 56.96 per 10,000 person years in the exposed cohort. Comparatively, there were 1737 incident T2DM cases, with an incidence rate of 161.23 per 10,000 person years in the comparison cohort. Compared to the comparison cohort, the NSAIDs cohort showed a significantly reduced risk of T2DM with an adjusted HR of 0.31 (95% CI, 0.26–0.36). Conclusions: Our cohort study provides longitudinal evidence that the use of NSAIDs was associated with a reduced risk of T2DM.

Associations between Conventional and Emerging Indicators of Dietary Carbohydrate Quality and New-Onset Type 2 Diabetes Mellitus in Chinese Adults

ObjectivesOur aim was to investigate the associations between dietary GI, CF and CQI and new-onset T2DM risk among Chinese adult.MethodsDietary glycemic index (GI), carbohydrate to fiber ratio (CF) and carbohydrate quality index (CQI) are conventional and emerging indicators for carbohydrate quality, respectively. Their associations with new-onset type 2 diabetes mellitus (T2DM) risk in Chinese adults remain unclear. We aimed to investigate the associations between dietary GI, CF and CQI and new-onset T2DM risk among Chinese adults. This prospective cohort study included 14,440 adults from the China Health and Nutrition Survey without cardiometabolic diseases at baseline. The associations between dietary GI, CF and CQI and T2DM risk were assessed using Cox proportional hazard regression analysis and dose–response relationships were explored using restricted cubic spline and threshold analyses.ResultsAfter a median follow-up duration of 9 years, a total of 1061 incident T2DM cases were identified. In fully adjusted models, higher dietary GI values were associated with reduced risk of T2DM, especially for Q4 (Q4 vs Q1: HR = 0.51; 95% CI: 0.38, 0.70; P-trend = 0.013), while CF and CQI were not significantly associated with incident T2DM. There were significant effect modifications of the association between dietary GI and T2DM risk by region and amount of carbohydrate intake (both P-interaction < 0.050). RCS analyses demonstrated significant non-linear trends of the associations between dietary GI and CF and T2DM risk (both P-overall < 0.001, P-nonlinear = 0.001), and threshold analyses showed that T2DM risk decreased and reached the bottom when dietary GI was 74.5 (73.4, 75.6) and CF was 27.3 (25.1, 29.6) (both P-log likelihood ratio < 0.001).ConclusionsThere were U-shaped relationships between dietary GI and CF and T2DM risk, indicating both dietary GI and CF should be controlled in a moderate range for T2DM prevention in Chinese adults. Further studies are required to confirm whether these indicators should be incorporated into dietary guidelines and Nutrient Facts panel labeling intended to help reduce T2DM risk in Chinese population.Funding SourcesThis study was funded by Shenzhen Science and Technology Program and the National Natural Science Foundation of China.

Type 2 diabetes epidemic and key risk factors in Qatar: a mathematical modeling analysis

IntroductionWe aimed to characterize and forecast type 2 diabetes mellitus (T2DM) disease burden between 2021 and 2050 in Qatar where 89% of the population comprises expatriates from over 150 countries.Research...

Simvastatin is associated with superior lipid and glycaemic control to atorvastatin and reduced levels of incident Type 2 diabetes, in men and women, in the UK Biobank.

IntroductionCardiovascular disease (CVD) is the leading cause of mortality in people with Type 2 diabetes mellitus (T2DM). Statins reduce low‐density lipoproteins and positively affect CVD outcomes. Statin type and dose have differential effects on glycaemia and risk of incident T2DM; however, the impact of gender, and of individual drugs within the statin class, remains unclear.AimTo compare effects of simvastatin and atorvastatin on lipid and glycaemic control in men and women with and without T2DM, and their association with incident T2DM.MethodsThe effect of simvastatin and atorvastatin on lipid and glycaemic control was assessed in the T2DM DiaStrat cohort. Prescribed medications, gender, age, BMI, diabetes duration, blood lipid profile and HbA1c were extracted from Electronic Care Record, and compared in men and women prescribed simvastatin and atorvastatin. Analyses were replicated in the UKBiobank in those with and without T2DM. The association of simvastatin and atorvastatin with incident T2DM was also investigated in the UKBiobank. Cohorts where matched for age, BMI and diabetes duration in men and women, in the UKBioBank analysis, where possible.ResultsSimvastatin was associated with better LDL (1.6 ± 0.6 vs 2.1 ± 0.9 mmol/L, p < .01) and total cholesterol (3.6 ± 0.7 vs 4.2 ± 1.0 mmol/L, p < .05), and glycaemic control (62 ± 17 vs 67 ± 19 mmol/mol, p < .059) than atorvastatin specifically in women in the DiaStrat cohort. In the UKBiobank, both men and women prescribed simvastatin had better LDL (Women: 2.6 ± 0.6 vs 2.6 ± 0.7 mmol/L, p < .05; Men: 2.4 ± 0.6 vs 2.4 ± 0.6, p < .01) and glycaemic control (Women:54 ± 14 vs 56 ± 15mmol/mol, p < .05; Men, 54 ± 14 vs 55 ± 15 mmol/mol, p < .01) than those prescribed atorvastatin. Simvastatin was also associated with reduced risk of incident T2DM in both men and women (p < .0001) in the UKBiobank.ConclusionsSimvastatin is associated with superior lipid and glycaemic control to atorvastatin in those with and without T2DM, and with fewer incident T2DM cases. Given the importance of lipid and glycaemic control in preventing secondary complications of T2DM, these findings may help inform prescribing practices.

Association between fetal famine exposure and risk of type 2 diabetes: a prospective cohort study.

The objective of this study was to explore the effects of fetal experience of famine on the onset of type 2 diabetes mellitus (T2DM) in adults. The analysis included 16 594 participants from the Kailuan Study who were free of diabetes at baseline (2006). According to the date of birth, the individuals born on October 1, 1962- September 30, 1964, were divided into the non-exposed group (used as the reference group), individuals born on October 1, 1959- September 30, 1961, were divided into the fetal exposure group, and the early childhood exposure group included those born on October 1, 1956- September 30, 1958. The cumulative incidence of T2DM for each group was calculated and compared among the 3 groups, and the Cox regression model was used to analyze the effects of fetal famine experience on the risk of diabetes. During a median 10.27 years (170 358 person-years) (2006-2017), 3509 incident T2DM cases were identified, with a cumulative incidence rate of 19.46%. The cumulative incidences of T2DM in the non-exposed, fetal exposure, and early childhood exposure groups were 17.38%, 20.85%, and 20.65%, respectively (P < 0.01). After adjusting for confounding factors, the hazard ratio (HR) of T2DM in the fetal exposure group was 1.222 (95% confidence interval: 1.087-1.374, P < 0.01), compared with the reference group. The association was modified by sex and hypertension (both P interaction less than 0.05). Fetal famine exposure may increase the risk of developing T2DM in adults. This association was more pronounced among women and those with hypertension. Novelty: The association was modified by sex and hypertension. Long follow-up time.

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 of parity/live birth number with incident type 2 diabetes among women: over 15\xa0years of follow-up in The Tehran Lipid and Glucose Study

BackgroundChildbearing may increase the future risk of developing type 2 diabetes mellitus (T2DM) in mothers. However, the issue is not clear completely and not investigated in the Middle East, a region with a high burden of T2DM. In the current study, we examined the association of parity/live birth number with incident T2DM among Iranian women.MethodsThe study population included 2552 women aged 30–65 years recruited in 1999–2001 and were followed for incident T2DM by 3-year intervals. Multivariable Cox proportional hazard models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the parity/live birth number for incident T2DM. Parity number was defined as the number of live childbirth (number of live birth) plus the number of stillbirth (defined as birth of an infant that died after the 20th week of pregnancy in the uterus).ResultsDuring a median follow-up of 15.4 years, 557 incident T2DM cases have occurred. After adjustment for potential T2DM risk factors and reproductive factors, each additional parity caused a 9% higher risk for incident T2DM. Moreover, compared to women with one parity, those with 3 and ≥ 4 parity had HRs of 1.73 [95% CI: 1.06–2.83] and 2.23 [1.36–3.65], respectively. After further adjustment for body mass index (BMI) and waist circumference, although the HRs were attenuated prominently, parity ≥ 4 was associated with significantly higher risk (HR: 1.72 [1.05–2.83]); even after further adjustment for triglycerides (TG)/ high-density lipoprotein cholesterol (HDL-C), the risk remained marginally significant (HR: 1.64 [1.00–2.70; P value: 0.051]). For the number of live birth, the results were also similar. Moreover, in a sensitivity analysis, when we considered BMI change during follow-up as another covariate, generally, the effect sizes did not change; the trend of HRs across categories of parity number remained marginally significant (P value: 0.064).ConclusionsDuring a long-term follow-up, after adjustment for potential T2DM risk factors, reproductive factors, obesity indices, and TG/HDL-C (insulin resistance surrogate), we demonstrated that higher parity/live birth numbers could be associated with increased risk of T2DM development among Iranian women. Moreover, even after further adjustment for BMI change, the suggestive higher risk was still found.

Plasma N-glycome shows continuous deterioration as the diagnosis of insulin resistance approaches

IntroductionPrediction of type 2 diabetes mellitus (T2DM) and its preceding factors, such as insulin resistance (IR), is of great importance as it may allow delay or prevention of onset of...

Associations of accumulated selected persistent organic pollutants in adipose tissue with insulin sensitivity and risk of incident type-2 diabetes

Continuous exposure to low doses of persistent organic pollutant (POPs), such as those occurring in the general population, might contribute to the burden of type 2 diabetes mellitus (T2DM). However, evidences from longitudinal studies are scarce. We aimed to explore the associations of accumulated POP exposure with the development of T2DM by means of 1) longitudinal associations with the 16-year incidence of the disease, and 2) complementary cross-sectional analyses with markers of glucose homeostasis at recruitment. Organochlorine pesticide and polychlorinated biphenyl (PCB) concentrations were analyzed in adipose tissue samples and incident T2DM cases were retrieved from clinical records. Homeostatic model assessment values of insulin sensitivity/resistance and β-cell function at recruitment were calculated. Linear and Cox-regression models were performed. In individuals with normal weight/overweight (n = 293), we observed positive dose–response relationships between the studied POPs and T2DM risk, particularly for hexachlorobenzene (HCB) [hazard ratio (HR): 3.96 for 4th quartile versus 1st quartile (Q1); confidence interval (CI) 95%: 0.79, 19.71]. PCB-180 showed a positive but seemingly non-linear association with T2DM risk [HR of 3er quartile (Q3) versus Q1: 6.48; CI 95%: 0.82, 51.29]. Unadjustment for body mass index considerably increased the magnitude of the associations. In the cross-sectional study (n = 180), HCB and PCB-180 were inversely associated with insulin sensitivity and positively associated with insulin resistance parameters. Our results suggest that a higher burden of specific POPs in adipose tissue may disrupt glucose homeostasis, possibly contributing to increase T2DM risk, especially in non-obese adults.

Replacing the consumption of red meat with other major dietary protein sources and risk of type 2 diabetes mellitus: a prospective cohort study

Greater consumption of red meat has been associated with a higher risk of type 2 diabetes mellitus (T2DM). A decreased intake of red meat and simultaneous increased intake of other high-protein foods may be associated with a lower risk of T2DM. These analyses of specific food replacements for red meat may provide more accurate dietary advice. We examined the association between a decrease in intake of red meat accompanied by an increase in other major dietary protein sources and risk of T2DM. We prospectively followed 27,634 males in the Health Professionals Follow-up Study, 46,023 females in the Nurses' Health Study, and 75,196 females in the Nurses' Health Study II. Diet was assessed by a validated FFQ and updated every 4 y. Cox proportional hazards models adjusted for T2DM risk factors were used to model the food replacements. We calculated HRs and 95% CIs for the T2DM risk associated with replacements of 1 daily serving of red meat with another protein source. During 2,113,245 person-years of follow-up, we identified 8763 incident T2DM cases from 1990 to 2013. In the pooled analyses, a decrease in total red meat intake during a 4-y period replaced with another common protein food was associated with a lower risk of T2DM in the subsequent 4-y period. The HR (95% CI) per 1 serving/d was 0.82 (0.75, 0.90) for poultry, 0.87 (0.77, 0.98) for seafood, 0.82 (0.78, 0.86) for low-fat dairy, 0.82 (0.77, 0.86) for high-fat dairy, 0.90 (0.81, 0.99) for eggs, 0.89 (0.82, 0.98) for legumes, and 0.83 (0.78, 0.89) for nuts. The associations were present for both unprocessed and processed red meat, although stronger for the replacement of processed red meat. Replacing red meat consumption with other protein sources was associated with a lower risk of T2DM.

A Pathophysiology of Type 2 Diabetes Unrelated to Metabolic Syndrome

Clinically, type 2 diabetes mellitus (T2DM) is heterogeneous, but the prevailing pathophysiologic hypothesis nevertheless contends that components of metabolic syndrome are central to all cases of T2DM. Here, we re-evaluated this hypothesis. We conducted a cross-sectional analysis of 138 women from the monocenter, post gestational diabetes study PPSDiab, 73 of which had incident prediabetes or T2DM. Additionally, we examined all the 412 incident cases of T2DM in phases 3 to 9 of the Whitehall II study in comparison to healthy controls. Our analysis included a medical history, anthropometrics, oral glucose tolerance testing, and laboratory chemistry in both studies. Additional analyses from the PPSDiab Study consisted of cardiopulmonary exercise testing, magnetic resonance imaging, auto-antibody testing, and the exclusion of glucokinase maturity-onset diabetes of the young. We found that 33 (45%) of the women with prediabetes or T2DM in the PPSDiab study displayed no components of metabolic syndrome. They reached no point for metabolic syndrome in the National Cholesterol Education Program Adult Treatment Panel III score other than hyperglycemia and, moreover, had levels of liver fat content, plasma triglycerides, high-density lipoprotein cholesterol, c-reactive protein, and blood pressure that were comparable to healthy controls. In the Whitehall II study, 62 (15%) of the incident T2DM cases fulfilled the same criteria. In both studies, these cases without metabolic syndrome revealed insulin resistance and inadequately low insulin secretion. Our results contradict the hypothesis that components of metabolic syndrome are central to all cases of T2DM. Instead, they suggest the common occurrence of a second, unrelated pathophysiology.