Microvascular burden and long-term risk of stroke and dementia in type 2 diabetes mellitus.

OBJECTIVE: To examine the associations between microvascular disease (MVD) and risk of stroke, dementia, and their major subtypes among individuals with type 2 diabetes mellitus (T2DM). METHODS: We included 26,173 participants with T2DM from the UK Biobank who had no known stroke or dementia at baseline. MVD burden was reflected by the presence of retinopathy, peripheral neuropathy, and chronic kidney disease. Cox regression models were used to estimate hazard ratios (HRs) and 95 % confidential intervals (CIs) of stroke and dementia associated with overall MVD burden and individual MVD. RESULTS: During a median follow-up of 11.5 years, 1103 incident stroke (964 ischemic and 269 hemorrhagic stroke) and 813 incident dementia (312 Alzheimer's disease and 304 vascular dementia) cases were identified. The risk of stroke, dementia, and their major subtypes all increased with an increasing number of MVD (all P-trend <0.001). The adjusted HRs (95 % CIs) comparing three with no MVD were 5.03 (3.16, 8.02) for all stroke, 4.57 (2.75, 7.59) for ischemic stroke, and 6.60 (2.65, 16.43) for hemorrhagic stroke. The corresponding estimates were 4.28 (2.33, 7.86) for all-cause dementia, 6.96 (3.02, 16.01) for Alzheimer's disease, and 3.81 (1.40, 10.42) for vascular dementia. Among the three MVD, chronic kidney disease showed the strongest associations with both stroke subtypes, while peripheral neuropathy was most strongly associated with both dementia subtypes. CONCLUSIONS: Risk of stroke, dementia, and their major subtypes increased with an increasing number of MVD. The associations of individual MVD with stroke and dementia varied substantially by types of MVD.

Relationship of microvascular complications and healthy lifestyle with all-cause and cardiovascular mortality in women compared with men with type 2 diabetes.

BACKGROUND: Sex differences exist in the prevalence of microvascular disease (MVD) and healthy-lifestyle adherence. Whether MVD and healthy lifestyles are associated with mortality risk similarly for women and men who have type 2 diabetes mellitus (T2DM) remains unknown. METHODS: The present study included 9992 women and 15,860 men with T2DM from the UK Biobank. MVDs included retinopathy, peripheral neuropathy, and chronic kidney disease. Healthy lifestyle factors consisted of ideal BMI, nonsmoking, healthy diet, regular exercise, and appropriate sleep duration. Sex-specific hazard ratios (HRs) of mortality associated with the MVDs or healthy lifestyles were calculated and women-to-men ratio of HRs (RHR) were further estimated, after multivariable adjustment for potential confounders. RESULTS: During a median of 12.7 years of follow-up, 4346 (1202 in women) all-cause and 1207 (254 in women) CVD deaths were recorded. The adjusted HRs (95% CI) of all-cause mortality for 1 additional increment of the MVDs were 1.71 (1.55, 1.88) for women and 1.48 (1.39, 1.57) for men, with an RHR of 1.16 (1.03, 1.30). The corresponding RHR was 1.36 (1.09, 1.69) for cardiovascular mortality. Adhering to a healthy lifestyle (≥4 vs. ≤1 lifestyle factor) was associated with an approximately 60%-70% lower risk of all-cause and cardiovascular mortality without sex differences (P-interaction >0.70). Furthermore, as compared with having no MVD and an unfavorable lifestyle, having ≥2 MVDs but a favorable lifestyle was not associated with a higher risk of all-cause mortality either in women (HR = 0.88; 95% CI: 0.49, 1.60) or in men (HR = 0.95; 95% CI: 0.64, 1.40), similarly when considering cardiovascular mortality. CONCLUSIONS: In T2DM, while MVDs are more strongly associated with mortality risk in women than in men, adhering to a favorable lifestyle is associated with a substantially lower risk of mortality and may eliminate the detrimental impact of MVDs in both sexes.

Effects of intensive glycemic control on microvascular outcomes in type 2 diabetes mellitus are modified by long-term HbA1c variability: A post hoc analysis of the ACCORD trial.

AIMS: To assess the impact of long-term visit-to-visit variability in HbA1c on microvascular outcomes in type 2 diabetes mellitus (T2DM), and its influence on the effects of intensive glycemic control. METHODS: Included were participants with T2DM enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) who had at least three measurements of HbA1c prior to new-onset microvascular outcomes, namely nephropathy, retinopathy and neuropathy. Variability in HbA1c was defined as the coefficient of variation (CV) across HbA1c measurements obtained from enrollment to the transition from intensive to standard glycemic therapy. RESULTS: During a median of 22,005, 23,121, and 13,080 person-years of follow-up, 2,905 nephropathy, 2,655 retinopathy, and 1,974 neuropathy cases were recorded, respectively. Median CV (IQR) was 7.91 % (5.66 %-10.76 %) in the standard treatment group and 9.79 % (7.32 %-13.35 %) in the intensive treatment group. In the standard treatment group, lower HbA1c-CV (the first versus the second quartile) was associated with a higher risk of all microvascular outcomes, while higher HbA1c-CV (the fourth quartile) was associated with a higher risk of nephropathy only. In the intensive treatment group, only higher HbA1c-CV was associated with a higher risk of developing the microvascular outcomes. Intensive therapy reduced all microvascular outcomes among individuals with lower HbA1c-CV, but increased the risk among those with the highest HbA1c-CV (all P values for interaction < 0.0001). For example, hazard ratios (95 % CI) of retinopathy comparing intensive with standard treatments were 0.65 (0.56-0.75), 0.84 (0.71-0.98), 0.97 (0.82-1.14) and 1.28 (1.08-1.53) across the lowest to the highest quartiles of HbA1c variability. CONCLUSIONS: The effects of intensive glycemic control on microvascular outcomes in T2DM appear to be modified by the variability of HbA1c during the treatment process, suggesting the significance of dynamic monitoring of HbA1c levels and timely adjustments to the therapeutic strategy among individuals with a high HbA1c variability.

Glomerular filtration rate estimated by differing measures and risk of all-cause mortality among Chinese individuals without or with diabetes: A nationwide prospective study.

BACKGROUND: Whether estimated glomerular filtration rates (eGFRs) by differing biomarkers are differentially associated with mortality or whether the associations differ by diabetes status remains unclear, especially in Chinese population. METHODS: We included 6995 participants without diabetes (mean age: 60.4 years) and 1543 with diabetes (mean age: 61.8 years). Each eGFR measure was divided into normal (≥90 mL/min/1.73 m2 ), modestly declined (60 to <90 mL/min/1.73 m2 ), and chronic kidney disease (CKD) (<60 mL/min/1.73 m2 ) groups. Cox proportional hazards models were used to estimate hazard ratio (HR) of all-cause mortality associated with each eGFR. RESULTS: Over a follow-up of 7 years, 677 and 215 deaths occurred among individuals without or with diabetes, respectively. Among those without diabetes, all measures of modestly declined eGFR were not associated with mortality, whereas CKD defined by eGFR cystatin C (eGFRcys) and eGFR creatinine (eGFRcr)-cys (HRs were 1.71 and 1.55, respectively) but not by eGFRcr were associated with higher risk of mortality. Among diabetes, all measures of modestly declined eGFR (HRs: 1.53, 1.56, and 2.09 for eGFRcr, eGFRcys, and eGFRcr-cys, respectively) and CKD (HRs: 2.57, 2.99, and 3.92 for eGFRcr, eGFRcys, and eGFRcr-cys, respectively) were associated with higher risk of mortality. Regardless of diabetes status, an addition of eGFRcys or eGFRcr-cys to traditional risk factors lead to a larger improvement in the prediction of all-cause mortality risk than adding eGFRcr. CONCLUSIONS: The association of eGFR with mortality risk appeared to be varied by its measures and by diabetes status among middle-aged and older Chinese, which needs to be considered in clinical practice.

Octenyl Succinic Anhydride-Modified Starch Attenuates Body Weight Gain and Changes Intestinal Environment of High-Fat Diet-Fed Mice.

Effects of octenylsuccinate (OS) starch on body composition and intestinal environment in high-fat diet-fed mice were investigated. C57BL/6J mice were treated with a regular-fat (RF) diet, a high-fat (HF) diet, or a high-fat diet supplemented with OS starch (HFOSS). Fecal short-chain fatty acids (SCFAs) were quantified using gas chromatography, and the fecal microbiota profile was analyzed by 16S rDNA sequencing. One-way ANOVA and metastats analysis were performed for statistical analysis. After 22 weeks of feeding, mice in the HFOSS group had significantly lower body weight, body fat, liver weight, and cumulative food intake than those in the HF group but higher than that of the RF group. Fecal total SCFA, acetic, propionic, and butyric acid concentrations were significantly higher in the HFOSS group than that in the HF and RF groups. OS starch intervention increased the relative abundance of Parabacteroides, Alistipes, and Ruminiclostridium_5 and decreased that of Tyzzerella, Oscillibacter, Desulfovibrio, and Anaerotruncus compared with the RF and HF groups. The relative abundance of Lachnospiraceae_UCG-006 in the HFOSS group was lower than that in the HF group but higher than that in the RF group. In conclusion, OS starch prevents fat accumulation in high-fat diet-fed mice and might provide potential health benefits due to its fermentability in the gut and its ability to regulate gut microbial community structure.

Preservation of Cognitive Function by Lepidium meyenii (Maca) Is Associated with Improvement of Mitochondrial Activity and Upregulation of Autophagy-Related Proteins in Middle-Aged Mouse Cortex.

Maca has been used as a foodstuff and a traditional medicine in the Andean region for over 2,000 years. Recently the neuroprotective effects of maca also arouse interest of researchers. Decrease in mitochondrial function and decline in autophagy signaling may participate in the process of age-related cognitive decline. This study aimed to investigate if maca could improve cognitive function of middle-aged mice and if this effect was associated with improvement of mitochondrial activity and modulation of autophagy signaling in mouse cortex. Fourteen-month-old male ICR mice received maca powder administered by gavage for five weeks. Maca improved cognitive function, motor coordination, and endurance capacity in middle-aged mice, accompanied by increased mitochondrial respiratory function and upregulation of autophagy-related proteins in cortex. Our findings suggest that maca is a newly defined nutritional plant which can improve mitochondrial function and upregulate autophagy-related proteins and may be an effective functional food for slowing down age-related cognitive decline.

Whole-grain intake and total, cardiovascular, and cancer mortality: a systematic review and meta-analysis of prospective studies.

BACKGROUND: The potential role of whole grain in preventing various mortality outcomes has been inconsistently reported in a wealth of prospective observational studies. OBJECTIVE: We evaluated the relations between whole-grain intake and risks of dying from any cause, cardiovascular disease (CVD), and cancer through a meta-analytic approach. DESIGN: Relevant studies were identified by searching PubMed and EMBASE databases and bibliographies of retrieved full publications. Summary RRs with 95% CIs were calculated with a random-effects model. RESULTS: Thirteen studies on total mortality (104,061 deaths), 12 on CVD mortality (26,352 deaths), and 8 on cancer mortality (34,797 deaths) were included. Three studies reported whole-grain intake, and the remaining studies reported whole-grain product intake. In the dose-response analysis in which the intake of whole-grain products was converted to the amount of whole grain, the summary RRs for an increment in whole-grain intake of 50 g/d were 0.78 (95% CI: 0.67, 0.91) for total mortality, 0.70 (95% CI: 0.61, 0.79) for CVD mortality, and 0.82 (95% CI: 0.69, 0.96) for cancer mortality. A similar reduction was observed for the mortality from ischemic heart disease (RR: 0.68; 95% CI: 0.55, 0.84) but not from stroke (RR: 0.93; 95% CI: 0.54, 1.62). There was evidence of nonlinear associations of whole-grain intake with total (P-nonlinearity < 0.001) and CVD mortality (P-nonlinearity <0.001), but not with cancer mortality (P-nonlinearity = 0.12), with the curves for the associations appearing slightly steeper at lower ranges (<35 g/d) of the intake than at higher ranges. CONCLUSIONS: Our findings suggest significant inverse relations between whole-grain intake and mortality due to any cause, CVD, or cancer. The findings support the recommendation of increasing whole-grain intake to improve public health.

Lipid content and fatty acids composition of mature human milk in rural North China.

To determine the lipid content and fatty acid (FA) composition of breast milk from fifty-two lactating women between ninth and twelfth lactation weeks in rural North China. The mothers were questioned on their dietary habits. Total milk lipids extracts were transmethylated and analysed using GLC to determine FA contents. The mean lipid content was 40.21 (sd 1.43) g/l. SFA constituted 35.92 % of the total FA. Medium-chain and long-chain SFA presented levels of 10.91 and 25.01 %, respectively. MUFA and PUFA constituted 32.59 and 19.97 % of the total FA, respectively. Oleic, linoleic and alpha-linolenic acid (ALA) presented contents of 31.26, 17.73 and 1.03 %, respectively. Arachidonic acid had a content of 0.30 %, while DHA content was 0.19 %. Not any form of trans FA were found in human milk samples. A maternal diet transition is proceeding in China. Further investigation on the analysis of human milk FA composition is needed to upgrade the human milk database in China.