Network Mendelian randomization study: exploring the causal pathway from insomnia to type 2 diabetes

IntroductionInsomnia is a novel pathogen for type 2 diabetes mellitus (T2DM). However, mechanisms linking insomnia and T2DM are poorly understood. In this study, we apply a network Mendelian randomization (MR) framework to determine the causal association between insomnia and T2DM and identify the potential mediators, including overweight (body mass index (BMI), waist-to-hip ratio, and body fat percentage) and glycometabolism (HbA1c, fasting blood glucose, and fasting blood insulin).Research design and methodsWe use the MR framework to detect effect estimates of the insomnia–T2DM, insomnia–mediator, and mediator–T2DM associations. A mediator between insomnia and T2DM is established if MR studies in all 3 steps prove causal associations.ResultsIn the Inverse variance weighted method, the results show that insomnia will increase the T2DM risk (OR 1.142; 95% CI 1.072 to 1.216; p=0.000), without heterogeneity nor horizontal pleiotropy, strongly suggesting that genetically predicted insomnia has a causal association with T2DM. Besides, our MR analysis provides strong evidence that insomnia is causally associated with BMI and body fat percentage. There is also suggestive evidence of an association between insomnia and the waist-to-hip ratio. At the same time, our results indicate that insomnia is not causally associated with glycometabolism. Higher BMI, waist-to-hip ratio, and body fat percentage levels are strongly associated with increased risk of T2DM.ConclusionsGenetically predicted insomnia has a causal association with T2DM. Being overweight (especially BMI and body fat percentage) mediates the causal pathway from insomnia to T2DM.

Waist-To-Hip Ratio Predicts Abnormal Overnight Oximetry in Men Independent of Body Mass Index

Background: Ambulatory overnight oximetry (OXI) has emerged as a cost-effective initial test for sleep disordered breathing. Obesity is closely associated with obstructive sleep apnea (OSA); however, whether body mass index (BMI) or waist-to-hip ratio (WHR) predicts abnormal overnight OXI remains unknown.Methods: We performed a retrospective cross-sectional study of 393 men seen in the Executive Health Program at Mayo Clinic in Rochester, Minnesota who underwent ambulatory overnight OXI ordered by preventive medicine physicians between January 1, 2004 through December 31, 2010. We compared participant/spouse-reported symptoms (sleepiness, snoring), physician indications for OXI (obesity, fatigue), Epworth Sleepiness Scale scores, anthropomorphic measurements (WHR, BMI), and comorbid medical conditions (hypertension, diabetes) with OXI results.Results: 295 of the 393 men who completed OXI had abnormal results. During multivariate analysis, the strongest independent predictor of abnormal OXI for men was WHR (≥1.0, OR = 5.59) followed by BMI (≥30.0 kg/m2, OR = 2.75), age (≥55 yrs, OR = 2.06), and the presence of snoring (OR = 1.91, P < 0.05 for all). A strong association was observed between WHR and abnormal OXI in obese (BMI ≥ 30.0 kg/m2, OR = 6.28) and non-obese (BMI < 29.9 kg/m2, OR = 6.42, P < 0.01 for both) men. Furthermore, 88 men with abnormal OXI underwent polysomnography with 91% being subsequently diagnosed with OSA.Conclusions: In ambulatory, predominantly middle-aged men undergoing preventive services evaluation many physician indications for OXI were not predictors of abnormal results; however, WHR strongly predicted abnormal OXI in obese and non-obese men. As such, we suggest middle-aged men who snore and have a WHR ≥1.0 should be directly referred to a sleep clinic for polysomnography.

U-Shaped Association between Waist-to-Hip Ratio and All-Cause Mortality in Stage 3–5 Chronic Kidney Disease Patients with Body Mass Index Paradox

The obesity paradox, referring to the association of high body mass index (BMI) with low all-cause mortality risk, is found in patients with chronic kidney disease (CKD). Central obesity is associated with metabolic syndrome and may have better prognostic value than BMI for all-cause mortality. Whether central obesity is associated with all-cause mortality in cases of obesity paradox in CKD patients remains unknown. We included 3262 patients with stage 3–5 CKD, grouped into five quintiles (Q1–5) by waist-to-hip ratio (WHR). Low WHR and BMI were associated with malnutrition and inflammation. In Cox regression, high BMI was not associated with all-cause mortality, but BMI < 22.5 kg/m2 increased the mortality risk. A U-shaped association between central obesity and all-cause mortality was found: WHR Q1, Q4, and Q5 had higher risk for all-cause mortality. The hazard ratio (95% confidence interval) of WHR Q5 and Q1 for all-cause mortality was 1.39 (1.03–1.87) and 1.53 (1.13–2.05) in male and 1.42 (1.02–1.99) and 1.28 (0.88–1.85) in female, respectively. Waist-to-height ratio and conicity index showed similar results. Low WHR or low BMI and high WHR, but not high BMI, are associated with all-cause mortality in advanced CKD.

Relationship between Serum Kallistatin and Afamin and Anthropometric Factors Associated with Obesity and of Being Overweight in Patients after Myocardial Infarction and without Myocardial Infarction

Extensive clinical and epidemiological evidence has linked obesity to a broad spectrum of cardiovascular disease (CVD), including coronary disease, heart failure, hypertension, cerebrovascular disease, atrial fibrillation, ventricular arrhythmias, and sudden death. In addition, increasing knowledge of regulatory peptides has allowed an assessment of their role in various non-communicable diseases, including CVD. The study assessed the concentration of kallistatin and afamin in the blood serum of patients after a myocardial infarction and without a cardiovascular event, and determined the relationship between the concentration of kallistatin and afamin and the anthropometric indicators of being overweight and of obesity in these groups. Serum kallistatin and afamin were quantified by ELISA tests in a cross-sectional study of 160 patients who were divided into two groups: study group (SG) (n = 80) and another with no cardiovascular event (CG) (n = 80). Serum kallistatin concentration was significantly higher in the SG (p < 0.001), while the level of afamin was significantly lower in this group (p < 0.001). In addition, a positive correlation was observed in the SG between the afamin concentration and the waist to hip ratio (WHR), lipid accumulation product (LAP) and the triglyceride glucose index (TyG index). In the CG, the concentration of kallistatin positively correlated with the LAP and TyG index, while the concentration of afamin positively correlated with all the examined parameters: body mass index (BMI), waist circumference (WC), hip circumference (HC), waist to hip ratio (WHtR), visceral adiposity index (VAI), LAP and TyG index. Serum kallistatin and afamin concentrations are associated with the anthropometric parameters related to being overweight and to obesity, especially to those describing the visceral distribution of adipose tissue and metabolic disorders related to excessive fatness.

Assessment of Risk Factors Associated with Cardiovascular Diseases in Overweight Women

The assessment of anthropometric variables has been shown to be useful as a predictor of cardiovascular risk in overweight and obese patients. The aim of this study was to determine the usefulness of the relationship between breast volume and body mass index as an indicator of cardiovascular risk in premenopausal women with overweight and mild obesity. A prospective observational study of 93 premenopausal women was performed. Evaluation of anthropometric measures included age, body mass index, waist and hip circumferences, breast projection, and ptosis. Cardiovascular risk factors were evaluated using the Framingham cardiovascular risk score, the triglycerides/HDL cholesterol ratio and the waist-hip ratio. Ninety-three women were included, with a mean 36.4 ± 7.5 years. Mean BMI was 27.3 ± 1.9 kg/m2, waist-to-Hip ratio was 0.8 ± 0.07, and mammary volume was 1045 ± 657.4 cm3. Mean body fat mass was 30.6 + 3.6% and mean visceral fat was 6.6 + 3.2%. The mean triglycerides to HDL ratio was 1.7 ± 0.8 and waist-to-hip ratio was 0.8 ± 0.07. Breast volume related to body mass index can be used as a predictor of cardiovascular risk in premenopausal women who are overweight and mildly obese.

Waist circumference, hip circumference, arm span, and waist-to-hip ratio high risk of polycystic ovarian syndrome

Background and Aims Polycystic ovarian syndrome is a reproductive problem of women with high prevalence cases accompanied by obesity conditions. Obesity condition can be seen from the size of waist circumference, hip circumference, arm span, and waist-to-hip ratio. This study aims to find out the risk factors between waist circumference size, hip circumference, arm span, and waist-to-hip ratio with polycystic ovarian syndrome. Methods This research is an analytical observation using a case-control approach conducted at Sekar Fertility Clinic and Poly Obgyn Dr Moewardi General Hospital Surakarta. Subjects were 150 consisting of 75 polycystic ovarian syndrome women and 75 normal fertile women. Sampling techniques used in this study are purposive sampling, researchers doing anthropometric measurements in the form of waist circumference, hip circumference, arm span, and waist-to-hip ratio simultaneously. The results were analyzed using Statistic Product and Service Solution 25. Results The results of the study obtained waist circumference with polycystic ovarian syndrome ( b = 3.002; CI 95% = 3.41–123.5; p = 0.001), hip circumference ( b = −2.671; CI 95% = 0.01–0.37; p = 0.002), arm span ( b = 5.318; CI 95% = 32.23–129.58; p < 0.001) and waist-to-hip ratio ( b = 1.761; CI 95% = 1.02–33.01; p = 0.047). Conclusion Waist circumference size, hip circumference, arm span, and waist-to-hip ratio correlate to a high risk of polycystic ovarian syndrome. Arm span is more dominant as an indicator of high risk to polycystic ovarian syndrome compared to waist circumference, hip circumference, and waist-to-hip ratio.

Significance of abdominal obesity and endothelial dysfunction marker in patients undergoing elective coronary stenting

Aim. To study the prognostic significance of abdominal obesity and endothelial dysfunction marker in patients undergoing elective coronary stenting.Material and Methods. The study included 225 patients with coronary artery disease at an average age of 57 [51; 63] years admitted to hospital for the purpose of performing planned endovascular myocardial revascularization through stenting. Depending on the presence or absence of adverse cardiovascular events, the patients were divided into two groups. Group 1 included 127 patients with an unfavorable course of disease; group 2 comprised 98 examined patients with a favorable course. The serum levels of endothelin-1 (ET-1), insulin, interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-10 (IL -10) and the ratio of waist to hip circumference (waist-to-hip ratio) were assessed directly before stenting the coronary arteries. The insulin resistance index (HOMA-IR) was calculated using the formula: fasting insulin (μIU/mL) × fasting blood glucose (mmol/L)/22.5. The lipid spectrum was determined by the enzymatic colorimetric method.Results. Correlation analysis of data in group 1 showed the presence of strong relationships of waist-to-hip ratio with body mass index (BMI) (r = 0.776; p = 0.000), ET-1 (r = 0.873; p = 0.000), and HOMA-IR index (r = 0.544; p = 0.000); weak relationships were found with basal glycemia (r = 0.238; p = 0.019), IL-10 (r = 0.295; p = 0.006), and IL-1 (r = 0.219; p = 0.047). Correlation analysis of data in group 2 showed the presence of week relationships of waist-to-hip ratio with BMI (r = 0.371; p = 0.002) and ET-1 (r = 0.471; p = 0.000) only.Conclusion. The study showed that ET-1 and the waist-to-hip ratio are strongly associated with the risk of adverse cardiovascular events after coronary stenting compared with other markers studied.

Influence of Waist-to-Hip Ratio on the Prognosis of Heart Failure Patients With Revascularized Coronary Heart Disease

Background: Heart failure (HF) is considered one of the most common complications of coronary heart disease (CHD), with a higher incidence of readmission and mortality. Thus, exploring the risk factors related to the prognosis is necessary. Moreover, the effect of the waist-to-hip ratio (WHR) on HF patients with revascularized CHD is still unclear. Thus, we aimed to assess the influence of WHR on the prognosis of HF patients with revascularized CHD.Methods: We collected data of HF patients with revascularized CHD who were referred to the Cardiac Rehabilitation Clinic of PLA Hospital from June 30, 2015, to June 30, 2019. Cox proportional hazard regression analysis was used to determine the relationship between WHR and prognosis of HF patients with revascularized CHD. Patients were divided into higher and lower WHR groups based on the cutoff WHR value calculated by the X-tile software. Cox regression analysis was used to analysis the two groups. We drew the receiver operating characteristic curve (ROC) of WHR and analyzed the differences between the two groups. Endpoints were defined as major adverse cardiac events (MACE) (including all-cause mortality, non-fatal myocardial infarction, unscheduled revascularization, and stroke).Results: During the median follow-up of 39 months and maximum follow-up of 54 months, 109 patients were enrolled, of which 91.7% were males, and the mean age was 56.0 ± 10.4 years. WHR was associated with the incidence of MACE in the Cox regression analysis (p = 0.001); an increase in WHR of 0.01 unit had a hazard ratio (HR) of 1.134 (95%CI: 1.057–1.216). The WHR cutoff value was 0.93. Patients in the higher WHR group had a significantly higher risk of MACE than those in the lower WHR group (HR = 7.037, 95%CI: 1.758–28.168). The ROC area under the curve was 0.733 at 4 years. Patients in the higher WHR group had a higher body mass index (BMI; 26.7 ± 3.5 vs. 25.4 ± 2.4, P = 0.033) than patients in the lower WHR group.Conclusions: WHR is an independent risk factor of the long-term prognosis of Chinese HF patients with revascularized CHD. Patients with WHR ≥ 0.93 require intensified treatment. Higher WHR is related to higher BMI and ΔVO2/ΔWR.