Associations of impaired glucose tolerance and sleep disorders with mortality among the US general population

IntroductionSleep disorders and short sleep duration are common symptoms among people with diabetes. However, the evidence is limited about the associations of post-challenge hyperglycemia and sleep quality or quantity with all-cause mortality in the US general population.Research design and methodsOur study included 8795 adults from the National Health and Nutrition Examination Survey 2005–2014. Mortality data were ascertained through 2015. Multivariable Cox proportional-hazards models were used to estimate adjusted HRs (aHRs) for all-cause mortality according to 2-hour plasma glucose levels during the 75 g oral glucose tolerance test—normal glucose tolerance (NGT), <140 mg/dL; impaired glucose tolerance (IGT), 140–199 mg/dL; and diabetes, ≥200 mg/dL. We then examined the associations of glucose tolerance status and self-reported physician-diagnosed sleep disorders (yes vs no) or sleep duration (<7 vs ≥7 hours) with all-cause mortality.ResultsDuring follow-up (median, 5.6 years), the diabetes group had a higher risk of all-cause mortality compared with the NGT group (aHR (95% CI)=1.93 (1.41 to 2.64)), but not the IGT group (aHR (95% CI)=1.19 (0.90 to 1.59)). When we categorized participants according to glucose tolerance status and sleep disorders, the IGT group with sleep disorders had a higher risk of all-cause mortality (aHR (95% CI)=2.03 (1.24 to 3.34)) compared with the NGT group without sleep disorders. Both diabetes groups with and without sleep disorders also showed high mortality risks. The results were consistent when we used sleep duration instead of sleep disorders.ConclusionsUsing the most updated US national data, we found a high risk of all-cause mortality among individuals with IGT having sleep disorders or short sleep duration as well as those with diabetes. Future investigations are needed to identify whether and what kind of sleep management is beneficial for people with impaired glucose metabolism to prevent early death.

Glucose tolerance stages in Cystic Fibrosis are idenfied by a unique pattern of defects of Beta-cell function

Aim To assess the order of severity of the defects of three direct determinants of glucose regulation, i.e., beta-cell function, insulin clearance and insulin sensitivity, in patients with CF categorized according their glucose tolerance status, including early elevation of mid-OGTT glucose values (&gt;140 and &lt; 200 mg/dL), named AGT140. Methods Two hundred and thirty-two CF patients aged 10-25 underwent OGTT. Beta-cell function and insulin clearance were estimated by OGTT mathematical modelling and OGTT-derived biomarkers of insulin secretion and sensitivity were calculated. The association between five glucose tolerance stages [NGT, AGT140, Indeterminate glucose Tolerance (INDET), impaired glucose tolerance (IGT), Cystic fibrosis related diabetes (CFRD)] and glucometabolic variables was assessed with general linear model. Results Beta-cell function and insulin sensitivity progressively worsened across glucose tolerance stages (p&lt;0.001) with AGT140 patients significantly differing from NGT (all p&lt;0.01). AGT140 and INDET showed a degree of beta-cell dysfunction similar to IGT and CFRD, respectively (all p&lt;0.01). Insulin clearance was not significantly associated with glucose tolerance stages (p=0.162). Each class of glucose tolerance was uniquely identified by a specific combination of defects of the direct determinants of glucose regulation. Conclusions In CF patients each of the five glucose tolerance stages shows a unique pattern of defects of the direct determinants of glucose regulation, with AGT140 patients significantly differing from NGT and being similar to IGT. These findings suggest to recognize AGT 140 as a distinct glucose tolerance class and to reconsider the grade of glucometabolic deterioration across glucose tolerance stages in CF.

Matcha Improves Metabolic Imbalance-Induced Cognitive Dysfunction

This study was conducted to assess the protective effect of extract of match (EM) on high-fat diet- (HFD-) induced cognitive deficits in male C57BL/6 mice. It was found that EM improved glucose tolerance status by measuring OGTT and IPGTT with HFD-induced mice. EM protected behavioral and memory dysfunction in Y-maze, passive avoidance, and Morris water maze tests. Consumption of EM reduced fat mass, dyslipidemia, and inflammation in adipose tissue. Also, EM ameliorated hepatic and cerebral antioxidant systems. EM improved the cerebral cholinergic system by regulating ACh contents and expression of AChE and ChAT. Also, EM restored mitochondrial function in liver and brain tissue. EM attenuated hepatic inflammatory effect, lipid synthesis, and cholesterol metabolism by regulating the protein expression of TNF-α, TNFR1, p-IRS-1, p-JNK, IL-1β, iNOS, COX-2, HMGCR, PPARγ, and FAS. Finally, EM regulated cognitive function and neuroinflammation in the whole brain, hippocampus, and cerebral cortex by regulating the protein expression of p-JNK, p-Akt, p-tau, Aβ, BDNF, IDE, COX-2, and IL-1β. These findings suggest that EM might be a potential source of functional food to improve metabolic disorder-associated cognitive dysfunction.

Impact of glucose tolerance status on the relationship between vascular endothelial growth factor D and mortality in patients with suspected coronary artery disease: a subanalysis of the ANOX study

Background Vascular endothelial growth factor D (VEGF-D) is a secreted glycoprotein that can act as lymphangiogenic and angiogenic growth factors through binding to its specific receptors, VEGFR-3 and VEGFR-2. VEGF-D signaling via VEGFR-3 plays an important role in lipoprotein metabolisms which may contribute to coronary artery disease (CAD). We recently reported that serum levels of VEGF-D are independently associated with mortality in patients with suspected or known CAD. However, the impact of glucose tolerance status on the relationship between VEGF-D and mortality in patients with suspected CAD is unclear. Methods Serum VEGF-D levels were measured in 1,717 patients with suspected CAD undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict CV events (ANOX) study, and followed up for 3 years. After excluding 67 patients with no HbA1c data, 1,650 patients were divided into 3 groups according to the glucose tolerance status: diabetes (DM, n=693), prediabetes (preDM, n=541) defined as an HbA1c of 5.7 to 6.4%, and normal glucose tolerance (NGT, n=416) defined as an HbA1c of 5.6% or less. The outcomes were total death, CV death, and major adverse CV events (MACE) defined as a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Results During the follow-up, 80 DM, 45 preDM, and 30 NGT patients died from any cause, 24 DM, 13 preDM, and 12 NGT died from CV disease, and 54 DM, 30 preDM, and 19 NGT developed MACE. After adjustment for established risk factors, VEGF-D levels were significantly associated with total death (hazard ratio [HR] for 1-SD increase, 1.28; 95% confidence interval [CI], 1.12–1.47), but not with CV death (HR, 1.20; 95% CI, 0.93–1.52) or MACE (HR, 1.23; 95% CI, 0.997–1.48) in DM; VEGF-D levels were not significantly associated with total death (HR, 0.97; 95% CI, 0.70–1.34), CV death (HR, 1.39; 95% CI, 0.92–2.11), or MACE (HR, 1.09; 95% CI, 0.74–1.50) in preDM; VEGF-D levels were not significantly associated with total death (HR, 1.34; 95% CI, 0.98–1.84), CV death (HR, 1.32; 95% CI, 0.78–2.13), or MACE (HR, 1.01; 95% CI, 0.66–1.46) in NGT. Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF-D levels further improved the prediction of total death (P=0.040 for continuous net reclassification improvement [NRI], P=0.007 for integrated discrimination improvement [IDI]), but not that of CV death or MACE in DM, while it did not significantly improved the prediction of total death, CV death, or MACE either in preDM or in NGT. Conclusions The VEGF-D level was independently associated with total death in DM, but not in preDM or in NGT. The relationship between VEGF-D and total mortality may depend on the presence of DM in patients with suspected CAD. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization.

Association between dietary patterns and prediabetes, undetected diabetes or clinically diagnosed diabetes: results from the KORA FF4 study

Purpose Diet is one of the most important modifiable risk factors for the development of type 2 diabetes. Here, we aim to identify dietary patterns and to investigate their association with prediabetes, undetected diabetes and prevalent diabetes. Methods The present study included 1305 participants of the cross-sectional population-based KORA FF4 study. Oral glucose tolerance test (OGTT) measurements together with a physician-confirmed diagnosis allowed for an accurate categorization of the participants according to their glucose tolerance status into normal glucose tolerance (n = 698), prediabetes (n = 459), undetected diabetes (n = 49), and prevalent diabetes (n = 99). Dietary patterns were identified through principal component analysis followed by hierarchical clustering. The association between dietary patterns and glucose tolerance status was investigated using multinomial logistic regression models. Results A Prudent pattern, characterized by high consumption of vegetables, fruits, wholegrains and dairy products, and a Western pattern, characterized by high consumption of red and processed meat, alcoholic beverages, refined grains and sugar-sweetened beverages, were identified. Participants following the Western pattern had significantly higher chances of having prediabetes (odds ratio [OR] 1.92; 95% confidence interval [CI] 1.35, 2.73), undetected diabetes (OR 10.12; 95% CI 4.19, 24.43) or prevalent diabetes (OR 3.51; 95% CI 1.85, 6.67), compared to participants following the Prudent pattern. Conclusion To our knowledge, the present study is one of the few investigating the association between dietary patterns and prediabetes or undetected diabetes. The use of a reference group exclusively including participants with normal glucose tolerance might explain the strong associations observed in our study. These results suggest a very important role of dietary habits in the prevention of prediabetes and type 2 diabetes.

Relationship Between Time‐Dependent Proteinuria and Risk of Stroke in Population With Different Glucose Tolerance Status

Background Proteinuria often changes and is known as a “time‐dependent exposure.” The effect of time‐dependent proteinuria on the risk of future stroke remains unclear. Proteinuria is often detected in patients with diabetes mellitus. The present study was designed to evaluate the association between time‐dependent proteinuria and the risk of stroke in a patient cohort with different glucose tolerance status. Methods and Results A total of 82 938 participants, who were free of myocardial infarction or stroke and underwent fasting blood glucose and urinary protein measurements at baseline in the Kailuan study, were enrolled. Proteinuria was determined using urine dipstick tests at baseline and subsequent follow‐ups. Time‐dependent proteinuria was defined as the status of urine protein updated through the follow‐up examinations, separately. Time‐dependent Cox regression models were used to analyze the relationship between time‐dependent proteinuria and the risk of stroke. During a median follow‐up of 8.37 years, 2538 participants developed stroke. After adjusting for confounding factors, the hazard ratio (95% CI) for stroke in time‐dependent proteinuria among all participants, and the normoglycemia, prediabetes, and diabetes mellitus populations were 1.68 (1.49–1.89), 1.73 (1.47–2.05), 2.15 (1.70–2.72), and 1.30 (1.03–1.65), respectively. There were interaction effects in patients with normoglycemia and prediabetes compared with those with diabetes mellitus. Findings were similar for ischemic and hemorrhagic strokes and were confirmed in sensitivity analyses. Conclusions Time‐dependent proteinuria is an independent risk factor of stroke, especially in the normoglycemia and prediabetes populations.