Multiple Metabolic Risk Factors Research Articles

Xiasangju alleviate metabolic syndrome by enhancing noradrenaline biosynthesis and activating brown adipose tissue.

Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other metabolic diseases. Recent evidence suggests that modulating adipose tissue to adaptive thermogenesis may offer therapeutic potential for MetS. Xiasangju (XSJ) is a marketed drug and dietary supplement used for the treatment of metabolic disease with anti-inflammatory activity. This study investigated the therapeutic effects of XSJ and the underlying mechanisms affecting the activation of brown adipose tissue (BAT) in MetS. The results revealed that XSJ ameliorated MetS by enhancing glucose and lipid metabolism, leading to reduced body weight and abdominal circumference, decreased adipose tissue and liver index, and improved blood glucose tolerance. XSJ administration stimulated catecholamine biosynthesis, increasing noradrenaline (NA) levels and activating NA-mediated proteins in BAT. Thus, BAT enhanced thermogenesis and oxidative phosphorylation (OXPHOS). Moreover, XSJ induced changes in gut microbiota composition, with an increase in Oscillibacter abundance and a decrease in Bilophila, Candidatus Stoquefichus, Holdemania, Parasutterella and Rothia. XSJ upregulated the proteins associated with intestinal tight junctions corresponding with lower serum lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α) monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) levels to maintain NA signaling transport. In summary, XSJ may alleviate MetS by promoting thermogenesis in BAT to ultimately boost energy metabolism through increasing NA biosynthesis, strengthening intestinal barrier integrity and reducing low-grade inflammation. These findings suggest XSJ has potential as a natural therapeutic agent for the treatment of MetS.

Progression to Obesity: Variations in Patterns of Metabolic Fluxes, Fat Accumulation, and Gastrointestinal Responses.

Obesity is a multifactorial disorder that is remarkably heterogeneous. It presents itself in a variety of phenotypes that can be metabolically unhealthy or healthy, associate with no or multiple metabolic risk factors, gain extreme body weight (super-responders), as well as resist obesity despite the obesogenic environment (non-responders). Progression to obesity is ultimately linked to the overall net energy balance and activity of different metabolic fluxes. This is particularly evident from variations in fatty acids oxidation, metabolic fluxes through the pyruvate-phosphoenolpyruvate-oxaloacetate node, and extracellular accumulation of Krebs cycle metabolites, such as citrate. Patterns of fat accumulation with a focus on visceral and ectopic adipose tissue, microbiome composition, and the immune status of the gastrointestinal tract have emerged as the most promising targets that allow personalization of obesity and warrant further investigations into the critical issue of a wider and long-term weight control. Advances in understanding the biochemistry mechanisms underlying the heterogenous obesity phenotypes are critical to the development of targeted strategies to maintain healthy weight.

1367-P: Type 2 Diabetes Mellitus and Obesity Amplifies Nonalcoholic Fatty Liver Disease Risk with Age

Nonalcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent in the general population with multiple known metabolic risk factors. There is limited evidence on the impact of age on the prevalence of hepatic steatosis and fibrosis, and their relationship to cardiometabolic risk factors. To this end, we recruited 761 patients 35-75 years of age, with and without T2DM, who underwent screening for NAFLD with laboratory tests and imaging by elastography (steatosis by controlled attenuation parameter [CAP]; fibrosis by liver stiffness measurement [LSM]). Patients were divided into 3 age groups: <45 years (young), 45-64 years (middle age), and ≥65 years old (older age), with results reported in this order. Of the 761 patients included, 21% (n=161) were young, 52% (n=397) middle age, and 27% (n=203) older. In the older age group, prevalence of obesity was lower (53% vs. 53% vs. 40%, p=0.01) but T2DM was higher (15% vs. 39% vs. 44%; p<0.01). Similarly, hypertension, atherogenic dyslipidemia, and use of antihypertensives and statins were more frequent in the older age group. Despite this, there were no differences in steatosis (CAP ≥274 dB/m: 50% vs. 54% vs. 52%, p=0.7). A marker of NAFLD disease activity (NIS4) worsened with increasing age (p<0.01). There was a trend for fibrosis (LSM≥7.0 kPa) to be higher in middle (11%) and older (8%) vs. younger (5%) age. After multivariable analysis (sex, race, ethnicity, BMI, A1c, cardiometabolic risk factors), BMI was associated with both steatosis and fibrosis in all age groups (p<0.01). There was a significant association between A1c as a continuous variable and steatosis only in the older age group (OR 2.8, 95% CI 1.6-4.9), while its association with fibrosis started at middle age (OR 1.3, 95% CI 1.1-1.7) and was stronger in older age (OR 1.8, 95% CI 1.01-3.2). Conclusion: Age was not associated with steatosis or fibrosis. BMI was the strongest predictor of hepatic steatosis and synergizes with T2DM for the development of fibrosis with age. Disclosure A. Sharma: None. E. Godinez Leiva: None. R. Lomonaco: None. E. Valdez Saenz: None. A. Ortiz Rocha: None. M.A. Gonzalez: None. S.A. Marangi: None. S. Shrestha: None. S.S. Shetty: None. J.T. Budd: None. S. Kalavalapalli: None. D. Barb: None. K. Cusi: Research Support; Echosens, Inventiva. Consultant; Poxel SA. Research Support; LabCorp, Zydus. Consultant; Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns.

Clustering of metabolic and behavioural risk factors for cardiovascular diseases among the adult population in South and Southeast Asia: findings from WHO STEPS data.

The aim of this study is to assess the current status of metabolic and behavioural risk factors for cardiovascular diseases among the adult population in South and Southeast Asia using World Health Organization (WHO) STEPS data. We used WHO STEPS surveys data in ten South and Southeast Asian countries. Weighted mean estimates of prevalence of five metabolic risk factors and four behavioural risk factors were calculated by country and overall region. We used random-effects meta-analysis to generate country and regional pooled estimates of metabolic and behavioural risk factors, using the DerSimonian and Laird inverse-variance method. Around 48,434 participants aged 18-69 years were included in this study. Overall 32.00% (95% CI: 31.15-32.36) of individuals in the pooled sample had one metabolic risk factor, 22.10% (95% CI: 21.73-22.47) had two, and 12.38% had three or more (95% CI: 9.09-14.00). Twenty-four percent (95% CI: 20.00-29.00) of individuals in the pooled sample had only one behavioural risk factor, 49.00% (95% CI: 42.00-56.00) had two, and 22.00% had three or more (95% CI: 16.00-29.00). Risk of high three or more metabolic risk factors was higher among women, those of older age, and those with a higher education. The existence of multiple metabolic and behavioural risk factors among the South and Southeast Asian population demand appropriate prevention strategies to halt the progress of non-communicable disease burden within the region. Not applicable.

Associations between serum clusterin levels and non-alcoholic fatty liver disease.

Clusterin is closely correlated with insulin resistance and its associated comorbidities. This study aimed to investigate the correlation between serum clusterin levels and non-alcoholic fatty liver disease (NAFLD) and further explore the mediating role of insulin resistance in this relationship. This study enrolled 195 inpatients (41 males and 154 females) aged 18-61 years. Twenty-four patients were followed up for 12 months after bariatric surgery. Serum clusterin levels were measured using a sandwich enzyme-linked immunosorbent assay. Fatty liver disease was diagnosed on the basis of liver ultrasonography. The fatty liver index (FLI) was calculated to quantify the degree of hepatic steatosis. The mediating role of homeostasis model assessment-insulin resistance (HOMA-IR) was assessed using mediation analysis. Participants with NAFLD had significantly higher serum clusterin levels than those without NAFLD (444.61 [325.76-611.52] mg/L versus 294.10 [255.20-373.55] mg/L, P < 0.01). With increasing tertiles of serum clusterin levels, the prevalence of NAFLD displayed an upward trend (P < 0.01). Multivariate linear regression analysis showed that serum clusterin levels were a positive determinant of FLI (standardized β = 0.271, P < 0.001) after adjusting for multiple metabolic risk factors. Serum clusterin levels significantly decreased after bariatric surgery (298.77 [262.56-358.10] mg/L versus 520.55 [354.94-750.21] mg/L, P < 0.01). In the mediation analysis, HOMA-IR played a mediating role in the correlation between serum clusterin levels and FLI; the estimated percentage of the total effect was 17.3%. Serum clusterin levels were associated with NAFLD. In addition, insulin resistance partially mediated the relationship between serum clusterin levels and FLI.

Clinical Phenotyping and the Application of Precision Medicine in MAFLD.

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Trajectories of metabolic risk factors during the development of type 2 diabetes in Chinese adults

AimsChina has the largest number of adults with diabetes. Although multiple metabolic risk factors (MRFs) are implicated in the development of diabetes, it remains unclear how they progress during the development of diabetes among Chinese. We examined trajectories of multiple MRFs among Chinese and identified the critical period when drastic changes occurred during the development of diabetes. MethodsThis prospective cohort study included participants since 2006–2007 in the Kailuan study. People attended biennial examinations until 2017 with additions of new participants at each examination cycle. The time when a participant first completed the examination was served as the baseline. A total of 122,659 participants without prevalent diabetes at baseline and with complete follow-up data were included. MRFs were collected via biennial physical examinations and laboratory measures. Incident diabetes cases were identified via biennial fasting glucose tests and self-reported physician-diagnosis. ResultsDuring up to 12 years of follow-up, 14,922 incident diabetes cases were identified. Compared with participants who did not develop diabetes, those who developed diabetes had more adverse levels of most MRFs at baseline and during follow-up. Abrupt increases in multiple MRFs (including fasting glucose, surrogate insulin resistance indicators, lipids, systolic blood pressure, pulse pressure, heart rate, alanine aminotransferase, and C-reactive protein) were observed 3 years before the diagnosis of diabetes. ConclusionsWe identified 3 years before diabetes diagnosis as a critical period when multiple MRFs experienced drastic changes. This would have implications for early monitoring and timely prevention for individuals who experience sudden adverse progression of multiple MRFs.

Depression and Metabolic Syndrome: A Narrative Review.

We reviewed the literature to investigate the relationship between depression and metabolic syndrome. Major depressive disorder is characterized by a low mood or a loss of interest for longer than two weeks. Metabolic syndrome describes multiple metabolic risk factors including obesity, insulin resistance, dyslipidemia, and hypertension. We divided our findings into environmental, genetic, epigenetic, and biological pathway links between depression and the different aspects of metabolic syndrome. We found various sources linking obesity and metabolic syndrome genetically, environmentally, biological pathway-wise, and, while not fully explored, epigenetically. Diabetes and depression were also found to be linked environmentally with both conditions increasing the risk of the other. Depression was also shown to be linked to cardiovascular complications as it increased the risk of occurrence of such complications in healthy people. These findings have led us to believe that there is a link between depression and metabolic syndrome on various levels, especially obesity.

The association between metabolic risk factors, nonalcoholic fatty liver disease, and the incidence of liver cancer: a nationwide population-based cohort study.

Liver cancer is a detrimental complication in patients with chronic viral hepatitis and alcoholic or nonalcoholic fatty liver disease (NAFLD). However, metabolic risk factors underlying NAFLD usually cause substantial differences in their clinical outcomes. Recently, several studies have used a novel definition of metabolic dysfunction-associated fatty liver disease (MAFLD) to reassess patients with NAFLD and pointed out the importance of metabolic risk factors. Since patients with NAFLD, MAFLD, or metabolic syndrome (MetS) have different burden of metabolic risk factors, it is crucial to decipher the risk of developing hepatic complications in these populations. Through a longitudinal nationwide cohort study, the risk of liver cancer was investigated in patients with MetS alone, NAFLD alone, overlap NAFLD/MAFLD, and coexisting MetS and NAFLD. The general characteristics, comorbidities, and incidence of liver cancer were also compared. Intriguingly, patients diagnosed with MetS alone did not have a significant risk of developing HCC compared to control individuals, while patients with NAFLD alone, NAFLD/MAFLD, and coexisting NAFLD and MetS exhibited 6.08-, 5.81-, and 15.33-fold risks of developing HCC, respectively. Apart from metabolic risk factors, renal function status and liver cirrhosis were the independent risk factors for the development of HCC among these groups. Our data emphasize that metabolic dysfunction has a significant impact on hepatocarcinogenesis in patients with NAFLD. Moreover, coexisting multiple metabolic risk factors would dampen the risk of developing HCC in patients with NAFLD. Closely tracing HCC formation through laboratory examination or imaging is crucial in these patients.

Abstract #1087690: Are We Missing NAFLD Fibrosis in Our Patients? One Endocrinologist's Clinic Experience

Patients with multiple metabolic risk factors and diabetes are at high risk for Nonalcoholic Fatty Liver Disease (NAFLD). Timely diagnosis of steatohepatitis and advanced fibrosis is crucial to reverse the disease process. Our goal was to estimate the proportion of patients at risk of advanced fibrosis among those seen by an endocrinologist for diabetes and dyslipidemia and to assess the real-world utility of proposed screening algorithms for these patients. This is a cross-sectional, descriptive study. All patients seen at the University of Washington Diabetes Institute and Lipid Clinic from 02/01/2021 to 05/15/2021 by a single endocrinologist were evaluated. We excluded patients with recent excessive alcohol intake, known history of viral hepatitis and those without updated laboratory data. Fibrosis-4 score (FIB-4) and NAFLD fibrosis score (NFS) were calculated on patients who met any of the following criteria: (1) ≥50 years old with diabetes (2) ≥2 metabolic risk factors (hyperlipidemia, hypertension, obesity, impaired glucose tolerance) (3) 1st degree relative with NAFLD fibrosis (4) steatosis on any imaging modality. Patients with a FIB-4 score ≥1.3 or NFS ≥-1.455 (consistent with indeterminate to high risk of advanced fibrosis) were recommended to have elastography. Out of 172 evaluated patients, 148 (86%) met screening criteria for NAFLD. 28 patients (19%) warranted elastography based on either FIB-4 score or NFS, with exclusion of those in whom elastography by Fibroscan is contraindicated, had established diagnosis of steatohepatitis, or elected not to address NAFLD. Among patients who met criteria for elastography, median liver enzymes, albumin and platelet counts were within the normal reference range. 18 patients completed elastography (16 by Fibroscan, 2 by ultrasound-based elastography) thus far. 5/18 (28%) patients had advanced fibrosis (≥F2; liver stiffness ≥7.5 kPa). 88% (14/16) had steatosis on Fibroscan. Incidentally, 7 patients (5% of the 148) had undergone Fibroscan without meeting criteria with FIB-4 or NFS, 100% of them had steatosis and 43% had advanced fibrosis. Majority of patients seen at the diabetes and lipid clinic by one endocrinologist met screening criteria for NAFLD and 19% of them warranted further evaluation with elastography. Approximately a third of patients evaluated by elastography had advanced fibrosis. Furthermore, 5% of patients (who did not even meet criteria for elastography) also had NAFLD and half of those patients had advanced fibrosis. This reveals that screening and risk assessment of patients seen by endocrinologists routinely can help detect most patients with NAFLD fibrosis in a timely manner.

Associations of health-related quality of life with sociodemographic characteristics, health, pain, and lifestyle factors, and motivation for changing lifestyle in adults living with chronic pain: a cross-sectional exploratory study.

We investigated the associations between health-related quality of life (HRQoL) and health, pain and lifestyle factors, as well as motivation for lifestyle changes, in adults living with chronic pain referred to a Danish pain centre. A total of 144 outpatients completed a questionnaire on HRQoL (EQ-5D-5L), health, pain, lifestyle factors (Body Mass Index [BMI], physical activity, smoking, alcohol, physical fitness, eating, sleep and stress) and motivation for lifestyle changes. We used multiple linear regression analyses to assess associations between HRQoL and the independent variables. The participants (age mean 50years, 81% females) had≥2 body pain sites (93%), BMI≥25 (64%), sedentary lifestyle (43%) and multiple (n≥2) elevated metabolic risk factors (58%). Most considered lifestyle important for HRQoL (72%) and expressed moderate to very high motivation for changing lifestyle (92%). Poorer HRQoL in the study population was significantly associated with higher pain intensity in the most painful body site (β=-0.316, p=0.001) and very poor sleep quality (β=-0.410, p=0.024). Serious-to-extreme problems in usual activities were associated with significantly poorer health (β=-0.328, p=0.030). Adults living with chronic pain participating in this survey had significantly lower self-evaluated HRQoL than the general population. Lower HRQoL was significantly associated with greater pain intensity and poor sleep quality. Serious-to-extreme problems in usual activities, such as work, study, housework, family and leisure, were associated with poorer self-evaluated health. We observed high frequencies of overweight, obesity, sedentary lifestyle, pain in multiple body sites and multiple lifestyle-related risk factors in the study population. Most participants felt motivated for changing lifestyle. Further interventions addressing pain alleviation, sleep quality, prevention of problems in usual activities and promotion of healthy lifestyle, e.g. physical activity and healthy eating, are needed to estimate the effect of a lifestyle-oriented approach on health and quality of life in people living with chronic pain. The results of this study will inform the research project reg. SJ-703, the Danish the Research Ethics Committee for Region Zealand, Denmark.

EFFECTS OF EXERCISE ON GLUCOSE AND LIPID METABOLISM IN ELDERLY PATIENTS

ABSTRACT Introduction: Metabolic syndrome is a condition in which multiple cardiovascular metabolic risk factors gather in the body. Objective: To explore the effects of exercise prescription on glucose and lipid metabolism in elderly patients with metabolic syndrome. Methods: A total of 85 elderly people were selected from a pension community. The influencing factors of physical activity were analyzed by the Pearson correlation analysis method, Mann-Whitneyu test and Kruskal-Wallish test. Finally, we quantitatively analyzed the influence and path of each factor on the physical activity of the elderly. Results: Among the 85 elderly people in nursing homes, 2 cases (1.1%) had a high level of physical activity, 70 cases (38.9%) had a medium level of physical activity, and 51 cases (60.0%) had a low level of physical activity. Conclusions: The improvement of glucose and lipid metabolism and healthy body fitness with the prescription of exercises of high oxygen + low resistance and that of exercises of high resistance + low oxygen is better than that with the prescription of exercises of full oxygen and full resistance. The improvement of sleep quality with the prescription of exercise with high oxygen and low resistance was better than that of exercise with complete oxygen, complete resistance and high resistance and low oxygen. Level of evidence II; Therapeutic studies - investigation of treatment results.

Metabolic syndrome and cognitive performance across the adult lifespan.

Metabolic Syndrome (MetS) is associated with increased rates of mortality and increased risk for developing dementia. Changes in brain structure and cognitive functioning have been reported within the literature. However, research examining cognitive performance in individuals with MetS is limited, inconclusive, and focuses primarily on older cohorts. As such, the effect of MetS on cognitive functioning earlier in the lifespan is unclear. This study aimed to investigate cognitive performance in young, middle-aged, and older adults with multiple metabolic and vascular risk factors in a sample of community dwelling participants (N = 128). Participants were administered a comprehensive neuropsychological battery and self-report measures. As expected, older adults performed more poorly than young and middle-aged adults across most assessments. Relative to controls, individuals with MetS reported greater hunger and disinhibited eating. MetS participants performed more poorly on Color-Word Interference: Inhibition. Additionally, when weight was accounted for, there was a significant relationship between MetS and select executive functioning tasks in middle-aged adults. These findings suggest that aspects of executive functioning may be impaired in MetS and could be further impacted by excess weight in middle-age. Future studies aimed at investigating potential causal relationships between metabolic and vascular risk factors, disinhibited eating, and executive dysfunction may provide insight into effective intervention targets to prevent MetS.

Idiopathic Non-Cirrhotic Portal Hypertension and Porto-Sinusoidal Vascular Disease: Review of Current Data.

Idiopathic non-cirrhotic portal hypertension (INCPH) is a clinicopathologic disease entity characterized by the presence of clinical signs and symptoms of portal hypertension (PH) in the absence of liver cirrhosis or known risk factors accountable for PH. Multiple hematologic, immune-related, infectious, hereditary and metabolic risk factors have been associated with this disorder. Still, the exact etiopathogenesis is largely unknown. The recently proposed porto-sinusoidal vascular disease (PSVD) scheme broadens the spectrum of the disease by also including patients without clinical PH who are found to have similar histopathologic findings on core liver biopsies. Three histomorphologic lesions have been identified as specific for PSVD to include obliterative portal venopathy, nodular regenerative hyperplasia and incomplete septal cirrhosis/fibrosis. However, these findings are often subtle, under-recognized and subjective with low interobserver agreement among pathologists. Additionally, the natural history of the subclinical forms of the disease remains unexplored. The clinical course is more favorable compared to cirrhosis patients, especially in the absence of clinical PH or liver dysfunction. There are no universally accepted guidelines in regard to diagnosis and treatment of INCPH/PSVD. Hence, this review emphasizes the need to raise awareness of this entity by highlighting its complex pathophysiology and clinicopathologic associations. Lastly, formulation of standardized diagnostic criteria with clinical validation is necessary to avoid misclassifying vascular diseases of the liver and to develop and implement targeted therapeutic strategies.

Suppressing Effect of Free Triiodothyronine on the Negative Association between Body Mass Index and Serum Osteocalcin Levels in Euthyroid Population

Previous studies found that thyroid hormones stimulate osteoblast-like cells to secrete osteocalcin. We aimed to investigate the association between serum thyroid hormone and serum osteocalcin in euthyroid population. The study recruited 1152 community-based euthyroid subjects (average age 59 ± 8 years), among whom 677 were women. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and osteocalcin were measured by electrochemiluminescence immunoassays. After adjusting for age and gender, partial correlation analysis showed that FT3 and FT3/FT4 were both positively correlated with body mass index (BMI) and serum osteocalcin levels (all P < 0.05) and BMI was negatively correlated with serum osteocalcin levels (P < 0.01), while FT4 and TSH were not correlated with serum osteocalcin levels (all P > 0.05). Age, gender, blood pressure, thyroid hormones, and multiple metabolic risk factors were included in the ridge regression model. FT3 and FT3/FT4 were independently and positively associated with serum osteocalcin levels (all P < 0.05), while BMI was independently and negatively associated with serum osteocalcin levels (P < 0.01). The mediating effect model showed that FT3 and FT3/FT4 suppressed the negative association between BMI and serum osteocalcin levels, with suppressing effects of 6.41% and 10.39%, respectively. In euthyroid subjects, both FT3 and FT3/FT4 were positively associated with serum osteocalcin levels, and they further suppressed the negative association between BMI and serum osteocalcin levels.

The results of 5-year atorvastatin therapy at the doses of 20–40 mg daily in metabolically compromised patients at very high risk

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is the main target for cardiovascular risk reduction. Statins remain the first-line therapy, however whether long-term statin use is safe and sufficient for achieving the new LDL-C goal (&amp;lt;1.4 mmol/l instead of &amp;lt;1.8 mmol/l) among patients at very high risk (VHR), especially those with multiple metabolic risk factors, remain uncertain. The purpose of our research was to estimate LDL-C lowering effect and occurrence of cardiovascular events (CVE) in ambulatory VHR patients who received atorvastatin for 5 years. Methods 107 patients (57 males and 50 females, mean (SD) age in years 59.8 (11.0) and 65.3 (8.5), respectively) with documented coronary artery disease who used atorvastatin at daily doses of 20 mg (n=40, baseline LDL-C 2.39 (0.53) mmol/l) or 40 mg (n=67, baseline LDL-C 4.05 (0.94) mmol/l) were included. The initial assessment included anthropometry, measuring of HbA1c and lipid profile (standard kits Human, Germany, LDL-C was calculated using the Friedewald's equation), and oral glucose tolerance test. During observation once annually patients were interviewing about prior hospitalizations due acute myocardial infarction, decompensated heart failure or stroke with further screening for type 2 diabetes mellitus (T2DM). Survival was analysed by Kaplan-Meier's method, using Cox's F-test; Fisher's exact test or Mann-Whitney U-test were used to compare independent samples; Wilcoxon matched pairs test was used for comparison of dependent samples. Results All participants had elevated baseline LDL-C, arterial hypertension and overweight or obesity (BMI ≥30 kg/m2 in 57%); 63.5% had prediabetes, 22.4% had first-detected T2DM, 54.2% had serum triglycerides &amp;gt;1.7 mmol/l, and 62.6% had low serum HDL-C adjusted to gender. Although in the end of observation, LDL-C levels in both atorvastatin regimens were significantly lower comparing to baseline (1.64 (0.20) and 2.20 (0.50) mmol/l, respectively, both P&amp;lt;0.0001), only 40% of patients who used 20 mg of atorvastatin and 49.3% of those who used 40 mg reached LDL-C target &amp;lt;1.8 mmol/l. Only 1.9% of participants reached LDL-C target &amp;lt;1.4 mmol/l. During observation, CVE were documented in 34 patients (n=9 (23.1%) vs n=25 (36.8%) in those who used 20 mg and 40 mg of atorvastatin, resp., P=0.072). This difference was significant when compared patients who achieved and did not achieved LDL-C target &amp;lt;1.8 mmol/l (14.3% vs 46.6%, resp., cumulative proportions surviving (CPS) 85.7% vs 53.5%, P=0.0001). Besides, during observation 29 new cases of T2DM were detected, (n=7 (22.6%) vs n=22 (42.3%) in those who used 20 mg and 40 mg of atorvastatin, resp., CPS 77.4% vs 57.0%, P=0.036). Conclusion After 5-year of atorvastatin use, less than 50% of metabolically compromised VHR patients had achieved LDL-C targets &amp;lt;1.8 mmol/l. Therapy was associated with dose-dependent risk of T2DM. To avoid statin dose escalation, combination therapy might be considered. Funding Acknowledgement Type of funding source: None

The Effects of a Functional Food Breakfast on Gluco-Regulation, Cognitive Performance, Mood, and Satiety in Adults.

A whole diet which combines multiple functional foods benefits metabolic risk factors and cognition, but evidence supporting meal to meal benefits, which individuals may find easier to implement, is limited. This study developed a functional food breakfast (FB), using polyphenol-rich ingredients selected for their gluco-regulating and cognitive-enhancing properties, and compared it to a control breakfast (CB). For study 1, total polyphenols were determined using the Folin–Ciocalteu method, and sugar release by in vitro digestion, in frozen and fresh samples. In study 2, healthy adults (n = 16) consumed an FB, CB and ready-to-eat breakfast cereal (RTEC) in a randomised crossover design. Glucose (GR) and insulin response (IR), satiety, mood and memory were measured over 180 min. The FB was a rich source of polyphenols (230 mg) compared to the CB (147 mg) (p < 0.05), and using frozen muffins did not compromise the polyphenol content or sugar release. Peak GR was highest after the RTEC (p < 0.05), and the insulin area under the curve (AUC) was lowest in the FB at 60, 120, 180 min and peak (p < 0.05). There were no effects on GR AUC, mood, satiety or memory. Reductions in GR peak and IR following consumption of the FB support the inclusion of functional ingredients at breakfast.

Association of Sugar-Sweetened Carbonated Beverage with the Alteration in Left Ventricular Structure and Diastolic Function

Background High consumption of sugar-sweetened carbonated beverage (SSCB) has been associated with multiple metabolic risk factors for cardiovascular disease. However, published data is scarce regarding the influence of SSCB consumption on left ventricular (LV) structure and diastolic function. The present study is to investigate the association of SSCB consumption with alteration in LV structure and diastolic function. Method Study subjects were 46,417 Koreans who received echocardiography as an item of health checkup. They were categorized into 4 groups by SSCB consumption based on one serving dose (200 ml) with never/almost never, <1 serving/week, 1 ≤ serving/week <3 and ≥3 serving/week. Multivariate logistic regression analysis was used in calculating adjusted odd ratio (OR) and 95% confidence interval (CI) (adjusted OR [95% CI]) for left ventricular hypertrophy, increased relative wall thickness (IRWT) and impaired LV relaxation with each group (reference: never/almost never consumption). Subgroup analysis was conducted by age of ≥40 and <40. Result Compared with never/almost never consumption, SSCB consumption ≥3 serving/week had the higher mean levels in body mass index, blood pressure and triglyceride despite of younger age. In fully adjusted analysis, SSCB consumption ≥3 serving/week was associated with IRWT (1.14 [1.02–1.27]) and impaired LV relaxation (1.23 [1.08–1.41]). This association was reinforced in age subgroup ≥40 years, but not statistically significant in age subgroup <40 years. Conclusion SSCB consumption ≥3 serving/week was associated with the increased probability of IRWT and impaired LV relaxation.

Significance of SGLT2 inhibitors: lessons from renal clinical outcomes in patients with type 2 diabetes and basic researches.

Diabetic kidney disease (DKD), a microvascular complication of diabetes, has been the leading cause of end-stage kidney disease (ESKD). Accordingly, patients with type 2 diabetes mellitus (T2DM) develop renal damage due to multiple metabolic and cardiorenal disease-related risk factors, including hyperglycemia, hypertension, dyslipidemia, hyperuricemia, and overnutrition/obesity. Despite multifactorial management including the administration of renin-angiotensin system inhibitors, patients often do not experience sufficient suppression of DKD progression and, thus, remain at risk for ESKD. Recent studies on cardiovascular outcomes among patients with T2DM have clearly shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin, canagliflozin, and dapagliflozin, have cardiorenal protective effects apart from their glucose-lowering effects. In particular, SGLT2 inhibitors have been found to improve renal outcomes, including ESKD, by slowing renal function decline and reducing urinary albumin excretion through their class effect. The proposed mechanisms for the renoprotective effects of SGLT2 inhibitors include the action of tubulo-glomerular feedback system and attenuation of hypoxia and metabolic stress in proximal tubular cells mediated through the inhibition of excessive glucose and sodium reabsorption, increased erythropoiesis, or increased ketone body production.

432-P: Creatinine-to-Cystatin C Ratio in Relation to Intima-Media Thickness in Patients with Type 2 Diabetes

Skeletal muscle mass (SM) was shown to be inversely related to cardiovascular disease (CVD) and mortality in some studies. However, the causal relationship between SM and CVD is not fully understood. Recently, creatinine-to-cystatin C ratio (Cr/cysC) has been suggested to be a useful surrogate marker for an estimation of SM. In the present study, we investigated whether Cr/cysC was related to intima-media thickness (IMT) in subjects with type 2 diabetes. A total of 459 patients with type 2 diabetes were recruited. Serum Cr and cysC were measured. All subjects were divided into three groups by gender-specific tertiles of Cr/cysC. We assessed carotid IMT using B-mode ultrasound. High IMT was defined as ≥ 75 percentiles of gender-specific maximal IMT. We checked body compositions using dual-energy X-ray absorptiometry. Patients with the highest tertile of Cr/cysC were younger and had higher prevalence of current smoking and regular exercise (RE) compared with those with the lowest. Also, they had higher values of Cr, fasting glucose (FG), HOMA-IR, and appendicular SM (ASM)/BMI, but had lower values of waist circumference (WC), cysC, Cr-based estimated glomerular filtration rate (Cr-eGFR), and IMT than those with the lowest. In the Pearson correlation, Cr/cysC was negatively related to age, BMI, and Cr-eGFR, but showed positive associations with FG and ASM/BMI in both genders. While WC and body fat percent were negatively associated with Cr/cysC in women alone. The odd ratios (ORs) for high IMT after adjusted for age were 0.76 (95% CI, 0.46-1.27) in the middle and 0.45 (95% CI, 0.25-0.79) in the highest, respectively. The OR in the highest was maintained significant after further adjustments for hypertension, current smoking, RE, BMI, WC, blood pressure, HDL, triglyceride, C-reactive protein, FG, HOMA-IR, and Cr-eGFR. In conclusion, the present study showed that higher Cr/cysC was significantly related to the protection of risk for high IMT independently of multiple metabolic risk factors. Disclosure J. Shin: None.