ResearchPad - cardiovascular-and-metabolic-risk https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Discovery of plasma biomarkers for predicting the severity of coronary artery atherosclerosis by quantitative proteomics]]> https://www.researchpad.co/article/elastic_article_9078 Cardiovascular disease (CVD) in patients with diabetes is the leading cause of death. Finding early biomarkers for detecting asymptomatic patients with CVD can improve survival. Recently, plasma proteomics—targeted selected reaction monitoring/multiple reaction monitoring analyses (MRM)—has emerged as highly specific and sensitive tools compared with classic ELISA methods. The objective was to identify differentially regulated proteins according to the severity of the coronary artery atherosclerosis.Research design and methodsA discovery cohort, a verification cohort and a validation cohort consisted of 18, 53, and 228 subjects, respectively. The grade of coronary artery stenosis was defined as a percentage of luminal stenosis of the major coronary arteries. Participants were divided into six groups, depending on the presence of diabetes and the grade of coronary artery stenosis. Two mass spectrometric approaches were employed: (1) conventional shotgun liquid chromatography tandem mass spectrometry for a discovery and (2) quantitative MRM for verification and validation. An analysis of the covariance was used to examine the biomarkers’ predictivity beyond conventional cardiovascular risks.ResultsA total of 1349 different proteins were identified from a discovery cohort. We selected 52 proteins based on the tandem mass tag quantitative analysis then summarized as follows: chemokine (C-X-C motif) ligand 7 (CXCL7), apolipoprotein C-II (APOC2), human lipopolysaccharide-binding protein (LBP) and dedicator of cytokinesis 2 (DOCK2) in diabetes; CXCL7, APOC2, LBP, complement 4A (C4A), vitamin D-binding protein (VTDB) and laminin β1 subunit in non-diabetes. Analysis of covariance showed that APOC2, DOCK2, CXCL7 and VTDB were upregulated and C4A was downregulated in patients with diabetes showing severe coronary artery stenosis. LBP and VTDB were downregulated in patients without diabetes, showing severe coronary artery stenosis.ConclusionWe identified significant associations between circulating APOC2, C4A, CXCL7, DOCK2, LBP and VTDB levels and the degree of coronary artery stenosis using the MRM technique. ]]> <![CDATA[Breakfast skipping is associated with persistently increased arterial stiffness in patients with type 2 diabetes]]> https://www.researchpad.co/article/Na1a35ff5-0efd-464c-8aa0-2a26fa8b84a6 While certain lifestyle habits may be associated with arterial stiffness, there is limited literature investigating the relationship between lifestyle habits and longitudinal changes in arterial stiffness in patients with type 2 diabetes mellitus (T2DM). This is an exploratory study to determine whether lifestyle habits, in addition to conventional atherosclerotic risk factors, are associated with increased arterial stiffness.Research design and methodsThe study participants comprised 734 Japanese outpatients with T2DM and no history of apparent cardiovascular diseases. Lifestyle habits were analyzed using self-reported questionnaires, and brachial-ankle pulse wave velocity (baPWV) was measured at baseline, and at years 2 and 5. A multivariable linear mixed-effects model was used to determine the predictive value of lifestyle habits and possible atherosclerotic risk factors for longitudinal change in baPWV.ResultsOver 5 years of follow-up, baPWV values significantly increased. In a multivariable linear mixed-effects model that adjusted for age and gender, a low frequency of breakfast intake was significantly associated with persistently high baPWV, independently of other lifestyle habits. Furthermore, in a multivariable linear mixed-effects model that included both lifestyle habits and possible atherosclerotic risk factors, a low frequency of breakfast intake remained the only independent predictive factor for persistently high baPWV. Subjects who ate breakfast less frequently tended to have additional unhealthy lifestyle habits and atherosclerotic risk factors.ConclusionsOur analyses suggest that breakfast skipping is an independent lifestyle habit that is associated with persistently increased arterial stiffness in patients with T2DM.Trial registration numberUMIN000010932. ]]> <![CDATA[Characteristics of undiagnosed diabetes in men and women under the age of 50 years in the Indian subcontinent: the National Family Health Survey (NFHS-4)/Demographic Health Survey 2015–2016]]> https://www.researchpad.co/article/N7651ee58-acbb-4637-9c97-5020d4a1522e Prior studies examining diabetes prevalence in India have found that nearly 50% of the diabetes population remains undiagnosed; however, the specific populations at risk are unclear.Research design and methodsFirst, we estimated the prevalence of undiagnosed diabetes in India for 750 924 persons between the ages of 15 years and 50 years who participated in the National Family Health Survey (NFHS-4)/Demographic Health Survey (2015–2016), a cross-sectional survey of all 29 states and 7 union territories of India. We defined ‘undiagnosed diabetes’ as individuals who did not know about their diabetes status but had high random (≥200 mg/dL) or fasting (≥126 mg/dL) blood glucose levels. Second, using Poisson regression, we associated 10 different factors, including the role of healthcare access, and undiagnosed diabetes. Third, we examined the association of undiagnosed diabetes with other potential comorbid conditions.ResultsThe crude prevalence of diabetes for women and men aged 15–50 years was 2.9%, 95% CI 2.9% to 3.1%, with self-reported diabetes prevalence at 1.7%, 95% CI 1.6 to 1.8. The overall prevalence of undiagnosed diabetes for 15–50 year olds was at 1.2%, 95% CI 1.2% to 1.3%. Forty-two per cent, 95% CI 40.7% to 43.4% of the individuals with high glucose levels were unaware of their diabetes status. Approximately 45%, 95% CI 42.9% to 46.4% of undiagnosed diabetes population had access to healthcare. Men, younger individuals, and those with lower levels of education were most at risk of being undiagnosed. Geographically, the Southern states in India had a significantly higher prevalence of undiagnosed diabetes despite having nearly universal access to healthcare. Risk factors combined with random glucose could predict undiagnosed diabetes (area under the curve of 97.8%, 95% CI 97.7% to 97.8%), Nagelkerke R2 of 66%).ConclusionClose to half (42%) of the people with diabetes in India are not aware of their disease status, and a large subset of these people are at risk of poor detection, despite having health insurance and/or having access to healthcare. Younger age groups and men are the most vulnerable. ]]> <![CDATA[In Utero Exposure to Maternal Hyperglycemia Increases Childhood Cardiometabolic Risk in Offspring]]> https://www.researchpad.co/article/5bfe79bad5eed0c4849338eb

OBJECTIVE

The objective of this study was to evaluate the effect of maternal hyperglycemia during pregnancy on cardiometabolic risk in offspring during early childhood.

RESEARCH DESIGN AND METHODS

A total of 970 mothers who had joined the Hyperglycemia and Adverse Pregnancy Outcome study were reevaluated, together with their child born during the study period, 7 years after delivery.

RESULTS

Offspring born to mothers diagnosed with gestational diabetes mellitus (GDM), as defined by the World Health Organization 2013 GDM criteria, had higher rates of abnormal glucose tolerance (4.7% vs. 1.7%; P = 0.04), higher rates of overweight or obesity, greater BMI, higher blood pressure (BP), lower oral disposition index, and a trend toward reduced β-cell function compared with those born to mothers without GDM. For each SD increase in maternal fasting, 1-h, and 2-h glucose levels on oral glucose tolerance tests (OGTTs) between 24 and 32 weeks of the index pregnancy, the risk of abnormal glucose tolerance in the offspring showed a corresponding increase (adjusted odds ratio [OR] 1.85–2.00). The associations were independent of BMI before pregnancy, childhood obesity, or being born large for gestational age. The area under the curve for glucose levels during the five-point OGTT increased to a similar extent in boys and girls with each SD increase in maternal 1-h and 2-h plasma glucose on OGTTs during pregnancy. All three maternal glucose levels were also associated with increased adjusted ORs for childhood overweight or obesity and adiposity among girls, but not boys.

CONCLUSIONS

Maternal hyperglycemia in pregnancy is independently associated with offsprings’ risk of abnormal glucose tolerance, obesity, and higher BP at 7 years of age. Its effect on childhood adiposity was apparent only in girls, not boys.

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<![CDATA[Intrahepatic Fat and Postprandial Glycemia Increase After Consumption of a Diet Enriched in Saturated Fat Compared With Free Sugars]]> https://www.researchpad.co/article/N9b831aec-c830-4288-b6a6-3abb79abda3b

OBJECTIVE

Debate continues regarding the influence of dietary fats and sugars on the risk of developing metabolic diseases, including insulin resistance and nonalcoholic fatty liver disease (NAFLD). We investigated the effect of two eucaloric diets, one enriched with saturated fat (SFA) and the other enriched with free sugars (SUGAR), on intrahepatic triacylglycerol (IHTAG) content, hepatic de novo lipogenesis (DNL), and whole-body postprandial metabolism in overweight males.

RESEARCH DESIGN AND METHODS

Sixteen overweight males were randomized to consume the SFA or SUGAR diet for 4 weeks before consuming the alternate diet after a 7-week washout period. The metabolic effects of the respective diets on IHTAG content, hepatic DNL, and whole-body metabolism were investigated using imaging techniques and metabolic substrates labeled with stable-isotope tracers.

RESULTS

Consumption of the SFA diet significantly increased IHTAG by mean ± SEM 39.0 ± 10.0%, while after the SUGAR diet IHTAG was virtually unchanged. Consumption of the SFA diet induced an exaggerated postprandial glucose and insulin response to a standardized test meal compared with SUGAR. Although whole-body fat oxidation, lipolysis, and DNL were similar following the two diets, consumption of the SUGAR diet resulted in significant (P < 0.05) decreases in plasma total, HDL, and non-HDL cholesterol and fasting β-hydroxybutyrate plasma concentrations.

CONCLUSIONS

Consumption of an SFA diet had a potent effect, increasing IHTAG together with exaggerating postprandial glycemia. The SUGAR diet did not influence IHTAG and induced minor metabolic changes. Our findings indicate that a diet enriched in SFA is more harmful to metabolic health than a diet enriched in free sugars.

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<![CDATA[Association of Insulin Dose, Cardiometabolic Risk Factors, and Cardiovascular Disease in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study]]> https://www.researchpad.co/article/Ne375e9a0-6b08-408f-a2b0-9af3839084b3

OBJECTIVE

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated the beneficial effects of intensive therapy on atherosclerosis and clinical cardiovascular disease (CVD) outcomes. The current analyses evaluated the relationship between longitudinal changes in insulin dose and CVD risk factors and outcomes.

RESEARCH DESIGN AND METHODS

A total of 1,441 participants were randomly assigned to intensive or conventional diabetes therapy during the DCCT. After an average of 6.5 years of follow-up, 96% of the surviving cohort enrolled in the EDIC observational study, which included annual visits with detailed medical history, physical examination, and laboratory testing. CVD events were adjudicated by a review committee. Generalized linear mixed models and Cox proportional hazards regression models were used to assess the association between insulin dose and cardiometabolic risk factors and CVD risk, respectively, over a total of 30 years.

RESULTS

Higher insulin doses were significantly associated with a less favorable cardiometabolic risk profile (higher BMI, pulse rate, and triglycerides and lower HDL cholesterol) with the exception of lower diastolic blood pressure and lower LDL cholesterol. In a minimally adjusted model, a 0.1 unit/kg body wt/day increase in insulin dose was associated with a 6% increased risk of any CVD (95% CI 3, 9). However, the association with insulin dose was no longer significant after adjustment for other CVD risk factors.

CONCLUSIONS

During DCCT/EDIC, higher insulin doses were associated with adverse trends in several cardiometabolic risk factors, even after multivariable adjustment, but not with incident CVD outcomes.

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<![CDATA[Incidence of type 2 diabetes in familial combined hyperlipidemia]]> https://www.researchpad.co/article/Nf5aeee3c-e131-491e-b1aa-df74ceb1a696

Objective

Familial combined hyperlipidemia (FCHL) is common among survivors of a premature myocardial infarction. FCHL patients are characterized by visceral obesity, fatty liver, and insulin resistance. The aim of the present study was to determine the incidence and determinants of type 2 diabetes (T2D) in a longitudinal cohort of FCHL pedigrees.

Research design and methods

FCHL patients, their unaffected relatives and spouses included in our baseline cohort in 1998–2005 (n=596) were re-invited to determine the incidence of self-reported T2D (that was confirmed by medical records), used as the primary outcome measure. The Fatty Liver Index (FLI) and Homeostasis Model Assessment Insulin Resistance (HOMA2-IR) were used as markers of fatty liver and insulin resistance, respectively. A subset of the original cohort underwent ultrasound of the liver, and subcutaneous and visceral fat in 2002–2005 (n=275; ‘ultrasound subcohort’).

Results

Follow-up data (median: 15 years) was acquired for 76%. The incidence rate of T2D was significantly higher in FCHL patients compared with spouses (19.2 per 1000 person-years vs 2.8 per 1000 person-years; HR : 6.3, 95% CI: 2.4 to 16.8), whereas no differences were observed between unaffected relatives and spouses (HR: 0.9, 95% CI: 0.3 to 2.6). Cox’s proportional hazard regression analyses showed that baseline HOMA2-IR and FLI≥60, but not waist circumference, BMI, or the FCHL affected state, were independently associated with incident T2D. Similar results were obtained in the ultrasound subcohort (median follow-up: 11 years), in which baseline HOMA2-IR and fatty liver (assessed by ultrasound) were independently associated with incident T2D.

Conclusion

This study further corroborates the suggestion that the liver plays a central role in the pathogenesis of cardiometabolic complications in FCHL. It supports periodical screening for T2D in this high-risk population.

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<![CDATA[Effect of CETP inhibition with evacetrapib in patients with diabetes mellitus enrolled in the ACCELERATE trial]]> https://www.researchpad.co/article/N07633b5b-f99a-4573-a0cf-52899dfbc8a8

Background

High-density lipoprotein (HDL) levels are inversely associated with cardiovascular risk. Cholesteryl ester transfer protein inhibition with evacetrapib results in a marked increase in HDL and reduction in low-density lipoprotein (LDL) levels. We evaluated the impact of treatment with evacetrapib versus placebo in the subset of 8236 patients with diabetes mellitus (DM) enrolled in the Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes trial.

Methods and results

Time to first occurrence of any component of the primary composite endpoint of cardiovascular death, myocardial infarction, stroke, revascularization, and hospitalization for unstable angina was compared among patients with DM randomized to treatment with evacetrapib (n=4127) or placebo (n=4109) over a median of 26 months of follow-up. The mean baseline LDL at initiation was 80 mg/dL with a mean baseline HDL of 44 mg/dL. In patients with DM, evacetrapib resulted in a 131% mean increase in HDL levels and a 32% mean decrease in LDL at 3 months that was sustained during the course of the trial. At 6 months, hemoglobin A1c (HbA1c) levels were lower with evacetrapib than placebo (7.08% vs 7.15%, p=0.023). Composite event rates were higher in patients with DM than without DM (Kaplan-Meier estimates: 15.2% vs 10.6%, HR 1.46, 95% CI 1.30 to 1.64, p<0.001). In the DM group, event rates for the composite endpoint (14.5% evacetrapib vs 16% placebo, HR 0.95, 95% CI 0.85 to 1.07, p=0.38) and individual components of the composite were similar for both evacetrapib and placebo groups. No significant treatment interaction between treatment assignment and diabetes status was noted.

Conclusion

Despite a favorable increase in HDL, and decreases in LDL and HbA1c levels in patients with DM, we observed no benefits of treatment with evacetrapib on prespecified clinical outcomes in this high-risk population.

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<![CDATA[Levels of ankle–brachial index and the risk of diabetes mellitus complications]]> https://www.researchpad.co/article/Ndd625572-8dd6-4aec-8dfd-f79820ee761c

Objective

We sought to compare the association of categorized ankle–brachial index (ABI) with mortality and complications of diabetes in persons with no symptoms of peripheral arterial disease (PAD) and in primary cardiovascular disease prevention.

Research design and methods

This is a retrospective cohort study of persons with type 2 diabetes aged 35–85 years, from 2006 to 2011. Data were obtained from the Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (SIDIAPQ). Participants had an ABI measurement that was classified into six categories. For each category of ABI, we assessed the incidence of mortality; macrovascular complications of diabetes: acute myocardial infarction (AMI), ischemic stroke, and a composite of these two; and microvascular complications of this metabolic condition: nephropathy, retinopathy, and neuropathy. We also estimated the HRs for these outcomes by ABI category using Cox proportional hazards models.

Results

Data from 34 689 persons with type 2 diabetes were included. The mean age was 66.2; 51.5% were men; and the median follow-up was 6.0 years. The outcome with the highest incidence was nephropathy, with 24.4 cases per 1000 person-years in the reference category of 1.1≤ABI≤1.3. The incidences in this category for mortality and AMI were 15.4 and 4.1, respectively. In the Cox models, low ABI was associated with increased risk and was significant from ABI lower than 0.9; below this level, the risk kept increasing steeply. High ABI (over 1.3) was also associated with significant increased risk for most outcomes.

Conclusions

The studied categories of ABI were associated with different risks of type 2 diabetes complications in persons asymptomatic for PAD, who were in primary cardiovascular prevention. These findings could be useful to optimize preventive interventions according to the ABI category in this population.

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<![CDATA[Prevalence and major risk factors of type 2 diabetes mellitus among adult psychiatric inpatients from 2005 to 2018 in Beijing, China: a longitudinal observational study]]> https://www.researchpad.co/article/N6e089d6e-9ac9-4a5e-9b37-03c2131abec5

Objective

We aim to investigate the prevalence, trends, and major risk factors of type 2 diabetes mellitus (T2DM) among adult psychiatric inpatients in Beijing, China.

Research design and methods

We did a longitudinal observational study using data from the Beijing Municipal Commission of Health and Family Planning Information Center, including 157 570 adult psychiatric inpatients in 19 specialized psychiatric hospitals from 2005 to 2018 in Beijing. Data on demographic characteristics and antipsychotic medication use were obtained from electronic health records. Schizophrenia, T2DM, and comorbidities were defined according to the International Classification of Diseases, 10th revision codes of discharge diagnosis. The overall prevalence of T2DM in adult psychiatric inpatients was calculated, and the annual prevalence of T2DM was calculated and adjusted to the overall participant population. Univariate and multivariate logistic regression analyses were performed to obtain crude ORs and adjusted ORs (aORs) on the risk of T2DM in patients with different demographic characteristics, schizophrenia, antipsychotic medication use, and different comorbidities. Age-specific prevalence of T2DM under a stratification of schizophrenia or other psychiatric disorders was calculated in the subgroup analysis.

Results

Out of 157 570 adult inpatients, 16 939 had T2DM, with a prevalence of 10.75% (95% CI 10.60% to 10.90%). The prevalence was 11.63% (95% CI 11.37% to 11.88%) among patients with schizophrenia and 10.17% (95% CI 9.98% to 10.37%) among patients with other psychiatric disorders. During 2005–2018, the prevalence of T2DM in adult patients increased over the years, from an adjusted prevalence of 5.20% in 2005, to 10.98% in 2010, 12.50% in 2015, and 12.71% in 2018. Results from the multivariate analysis showed that increasing age, diagnosis of schizophrenia (aOR=1.23, 95% CI 1.18 to 1.29), and comorbidities of hypertension (aOR=3.09, 95% CI 2.97 to 3.22), lipid disorders (aOR=1.95, 95% CI 1.88 to 2.04), and fatty liver (aOR=1.93, 95% CI 1.84 to 2.03) were major risk factors of T2DM in adult psychiatric inpatients.

Conclusions

The prevalence of T2DM was high among adult psychiatric inpatients in Beijing, China. Elderly patients, those with schizophrenia, and those with hypertension, lipid disorders, and fatty liver had higher prevalence of T2DM. Prevention and treatment of T2DM are of utmost relevance in hospitalized psychiatric patients.

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<![CDATA[Metabolic characteristics of Africans with normal glucose tolerance and elevated 1-hour glucose: insight from the Africans in America study]]> https://www.researchpad.co/article/Nd95b534f-a04c-4656-af99-3d138b38710d

Introduction

Risk of insulin resistance, dyslipidemia, diabetes and cardiac death is increased in Asians and Europeans with normal glucose tolerance (NGT) and 1-hour glucose ≥8.6 mmol/L. As African descent populations often have insulin resistance but a normal lipid profile, the implications for Africans with NGT and glucose ≥8.6 mmol/L (NGT-1-hour-high) are unknown.

Objective

We performed oral glucose tolerance tests (OGTTs) in 434 African born-blacks living in Washington, DC (male: 66%, age 38±10 years (mean±SD)) and determined in the NGT group if either glucometabolic or lipid profiles varied according to a 1-hour-glucose threshold of 8.6 mmol/L.

Methods

Glucose tolerance category was defined by OGTT criteria. NGT was subdivided into NGT-1-hour-high (glucose ≥8.6 mmol/L) and NGT-1-hour-normal (glucose <8.6 mmol/L). Second OGTT were performed in 27% (119/434) of participants 10±7 days after the first. Matsuda Index and Oral Disposition Index measured insulin resistance and beta-cell function, respectively. Lipid profiles were obtained. Comparisons were by one-way analysis of variance with Bonferonni corrections for multiple comparisons. Duplicate tests were assessed by к-statistic.

Results

One-hour-glucose ≥8.6 mmol/L occurred in 17% (47/272) with NGT, 72% (97/134) with pre-diabetes and in 96% (27/28) with diabetes. Both insulin resistance and beta-cell function were worse in NGT-1-hour-high than in NGT-1-hour-normal. Dyslipidemia occurred in both the diabetes and pre-diabetes groups but not in either NGT group. One-hour glucose concentration ≥8.6 mmol/L showed substantial agreement for the two OGTTs (к=0.628).

Conclusions

Although dyslipidemia did not occur in either NGT group, insulin resistance and beta-cell compromise were worse in NGT-1 hour-high. Subdividing the NGT group at a 1-hour glucose threshold of 8.6 mmol/L may stratify risk for diabetes in Africans.

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<![CDATA[Abdominal obesity and hypertension are correlated with health-related quality of life in Taiwanese adults with metabolic syndrome]]> https://www.researchpad.co/article/N18c4e761-1d27-43e9-8763-b82f3ef23fd3

Objective

Metabolic syndrome (MetS) gains more attention due to high prevalence of obesity, diabetes and hypertension among adults. Although obesity, diabetes and hypertension can certainly compromise health-related quality of life (HRQoL), the correlations of sociodemographic factors, quality of life and MetS remains unclear. This study aims to investigate the association between HRQoL and MetS in an Asian community of the sociodemographic characteristics.

Research design and methods

We performed a cross-sectional study by recruiting 2588 Taiwanese patients aged ≥30 years between August 2015 and August 2017. Sociodemographic data and anthropometric variables were obtained from medical records and physical examination. Meanwhile, HRQoL was assessed by 36-Item Short-Form Health Survey questionnaires.

Results

The overall prevalence of MetS was 32.8%. Multivariate analysis revealed that age ≥65 years (OR=1.987, p<0.001), body mass index (BMI) ≥24 kg/m2 (OR=7.958, p<0.001), low educational level (OR=1.429, p=0.014), bad self-perceived health status (OR=1.315, p=0.01), and betel nut usage (OR=1.457, p=0.048) were associated with the development of MetS. For patients with MetS, the physical and mental health domains of HRQoL are negatively correlated with abdominal obesity and hypertension, respectively.

Conclusions

Adult MetS in Taiwan was associated with certain sociodemographic factors including older age, high BMI, low educational level, bad self-perceived health status, and betel nut use. Abdominal obesity and hypertension was correlated with HRQoL in patients with MetS.

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<![CDATA[Insulin resistance, beta-cell function, adipokine profiles and cardiometabolic risk factors among Chinese youth with isolated impaired fasting glucose versus impaired glucose tolerance: the BCAMS study]]> https://www.researchpad.co/article/N2fe55ffb-6f66-4e9c-9f7e-61bdbed046b0

Objective

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) may convey disparate risks of metabolic consequences. Fasting plasma glucose (FPG), while an expedient screening procedure, may not adequately assess metabolic risk, particularly among youths. In order to inform a strategy for screening Chinese youth for pre-diabetes, we examined the relative value of IFG versus IGT to define metabolic risk by assessing their association with insulin resistance, beta-cell dysfunction, adverse adipokine profiles and other cardiometabolic risk factors.

Research design and methods

We recruited 542 subjects (age 14–28 years) from the Beijing Child and Adolescent Metabolic Syndrome study for an in-depth assessment of cardiometabolic risk factors, including a 2-hour oral glucose tolerance test, liver ultrasound and serum levels of four adipokines.

Results

FPG failed to identify nearly all (32/33) youths with IGT, whereas 2-hour plasma glucose (2 h PG) missed 80.8% (21/26) of subjects with IFG. Impaired beta-cell function was evident from decreased oral disposition indices in those with isolated impaired fasting glucose (iIFG) or isolated impaired glucose tolerance (iIGT) versus normal glucose tolerance (NGT) (all p<0.001), whereas reduced insulin sensitivity (Matsuda) index was most pronounced in the iIGT group (p<0.01). Moreover, alterations in adipokine levels (fibroblast growth factor 21, adiponectin and leptin/adiponectin ratio) were associated with iIGT (p<0.05) but not iIFG. Youths with iIGT had a 2-fold to 32-fold increased incidence of hypertriglyceridemia, hypertension and metabolic syndrome (MetS) compared with those with NGT. In addition, subgroup analyses of participants with normal FPG revealed that the odds of having IGT increased 3-fold to 18-fold among those with elevated TGs, hypertension, moderate-to-severe non-alcoholic fatty liver disease or MetS.

Conclusions

Chinese youth with iIGT exhibit a higher cardiometabolic risk profile than those with iIFG. Thus, 2 h PG is preferred over FPG to identify the pre-diabetes phenotype at greatest risk of subsequent development of cardiovascular disease.

Trial registration number

NCT03421444.

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<![CDATA[Adequate 25-hydroxyvitamin D levels are inversely associated with various cardiometabolic risk factors in Chinese children, especially obese children]]> https://www.researchpad.co/article/N52c8257e-ac94-4323-b64f-3b8c381f9eac

Objective

Vitamin D deficiency has recently evolved as a major public health issue worldwide. But the relationship between vitamin D and cardiovascular health in children remains unclear. Accordingly, we aimed to examine the associations between 25-hydroxyvitamin D (25(OH)D) concentrations and cardiometabolic risk factors, and to assess the possible effect modification of obesity on the associations in a Chinese pediatric population.

Research design and methods

A cross-sectional sample of 6091 children aged 6–18 years was obtained using a cluster sampling method. The 25(OH)D concentrations, and metabolic risk factors, including waist to height ratio, blood pressure, blood lipids, fasting blood glucose (FBG), and insulin were measured. Adjusted ORs and multiplicative or additive interaction were calculated to assess the associations and effect modification, respectively.

Results

Triglycerides, FBG, insulin, and homeostasis model assessment of insulin resistance were inversely associated with 25(OH)D concentrations (p<0.05) in both sexes. The OR of hyperglycemia among individuals with insufficient vitamin D was higher than those with adequate vitamin D after adjusting for covariates (OR: 1.47; 95% CI 1.26 to 1.70). Moreover, girls with insufficient vitamin D had significantly higher odds for hypertension and high total cholesterol than those with adequate vitamin D, which was not observed in boys. Thirty-two percent (95% CI 14% to 51%) of the increased odds of hyperglycemia can be explained by the interaction between insufficient vitamin D and obesity.

Conclusions

Vitamin D insufficiency is associated with increased odds of various cardiometabolic risk factors in Chinese children and has a synergistic effect on hyperglycemia with obesity.

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<![CDATA[Advanced Glycation End Products, Oxidation Products, and Incident Cardiovascular Events in Patients With Type 2 Diabetes]]> https://www.researchpad.co/article/5c8eeb26d5eed0c484ef90a0

OBJECTIVE

The goal of this study was to determine whether plasma levels of advanced glycation end products (AGE) and oxidation products (OP) predict the incidence of cardiovascular disease (CVD) in type 2 diabetes.

RESEARCH DESIGN AND METHODS

Five specific AGE (methylglyoxal hydroimidazolone, carboxymethyl lysine, carboxyethyl lysine, 3-deoxyglucosone hydroimidazolone, and glyoxal hydroimidazolone) and two OP (2-aminoadipic acid and methionine sulfoxide [MetSO]) were measured at baseline in two intensive glucose-lowering studies: 1) a subcohort of the Veterans Affairs Diabetes Trial (VADT) (n = 445) and 2) a nested case-control subgroup from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (n = 271).

RESULTS

Increased levels of several AGE and OP were associated with older age, decreased kidney function, previous CVD, and longer diabetes duration, but not with hemoglobin A1c. In the VADT, increased risk of incident CVD events (n = 107) was associated with lower MetSO after adjusting for age, race/ethnicity, sex, prior CVD event, kidney function, treatment assignment, and diabetes duration (hazard ratio [HR] 0.53; 95% CI 0.28–0.99; P = 0.047). Individuals with both low MetSO and high 3-deoxyglucosone hydroimidazolone concentrations were at highest risk for CVD (HR 1.70; P = 0.01). In the ACCORD study, those with incident CVD events (n = 136) had lower MetSO (by 14%; P = 0.007) and higher glyoxal hydroimidazolone and carboxymethyl lysine (by 18% and 15%, respectively; P = 0.04 for both); however, only the difference in MetSO remained significant after adjustment for prior CVD event (P = 0.002).

CONCLUSIONS

Lower levels of MetSO and higher levels of select AGE are associated with increased incident CVD and may help account for the limited benefit of intensive glucose lowering in type 2 diabetes.

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<![CDATA[Risk Assessment in Patients With Diabetes With the TIMI Risk Score for Atherothrombotic Disease]]> https://www.researchpad.co/article/5c8eeb24d5eed0c484ef908d

OBJECTIVE

Improved risk assessment for patients with type 2 diabetes and elevated cardiovascular (CV) risk is needed. The Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P) predicts a gradient of risk in patients with prior myocardial infarction (MI) but has not been evaluated in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

CV event rates were compared by baseline TRS 2°P in 16,488 patients enrolled in SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53) with type 2 diabetes and high CV risk or established CV disease. Calibration was tested in the diabetes cohort from the REACH (REduction of Atherothrombosis for Continued Health) Registry.

RESULTS

TRS 2°P revealed a robust risk gradient for the composite of CV death, MI, and ischemic stroke in the full trial population, with 2-year event rates of 0.9% in the lowest- and 19.8% in the highest-risk groups (Ptrend < 0.001). A clear risk gradient was present within the subgroups of all coronary artery disease (CAD), CAD without prior MI, CAD with prior MI, peripheral artery disease, and prior stroke (Ptrend < 0.001 for each), with consistent risk relationships across subgroups. The C-statistic (0.71 for CV death and 0.66 for the composite end point) was consistent in each subgroup. There was close calibration with the type 2 diabetes cohort from the REACH Registry (goodness-of-fit P = 0.78).

CONCLUSIONS

The expanded TRS 2°P provides a practical and well-calibrated risk prediction tool for patients with type 2 diabetes.

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<![CDATA[Characteristics Associated With Decreased or Increased Mortality Risk From Glycemic Therapy Among Patients With Type 2 Diabetes and High Cardiovascular Risk: Machine Learning Analysis of the ACCORD Trial]]> https://www.researchpad.co/article/5c8eeb2bd5eed0c484ef916f

OBJECTIVE

Identifying patients who may experience decreased or increased mortality risk from intensive glycemic therapy for type 2 diabetes remains an important clinical challenge. We sought to identify characteristics of patients at high cardiovascular risk with decreased or increased mortality risk from glycemic therapy for type 2 diabetes using new methods to identify complex combinations of treatment effect modifiers.

RESEARCH DESIGN AND METHODS

The machine learning method of gradient forest analysis was applied to understand the variation in all-cause mortality within the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (N = 10,251), whose participants were 40–79 years old with type 2 diabetes, hemoglobin A1c (HbA1c) ≥7.5% (58 mmol/mol), cardiovascular disease (CVD) or multiple CVD risk factors, and randomized to target HbA1c <6.0% (42 mmol/mol; intensive) or 7.0–7.9% (53–63 mmol/mol; standard). Covariates included demographics, BMI, hemoglobin glycosylation index (HGI; observed minus expected HbA1c derived from prerandomization fasting plasma glucose), other biomarkers, history, and medications.

RESULTS

The analysis identified four groups defined by age, BMI, and HGI with varied risk for mortality under intensive glycemic therapy. The lowest risk group (HGI <0.44, BMI <30 kg/m2, age <61 years) had an absolute mortality risk decrease of 2.3% attributable to intensive therapy (95% CI 0.2 to 4.5, P = 0.038; number needed to treat: 43), whereas the highest risk group (HGI ≥0.44) had an absolute mortality risk increase of 3.7% attributable to intensive therapy (95% CI 1.5 to 6.0; P < 0.001; number needed to harm: 27).

CONCLUSIONS

Age, BMI, and HGI may help individualize prediction of the benefit and harm from intensive glycemic therapy.

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<![CDATA[Validation of Risk Equations for Complications of Type 2 Diabetes (RECODe) Using Individual Participant Data From Diverse Longitudinal Cohorts in the U.S.]]> https://www.researchpad.co/article/5c8eeb27d5eed0c484ef9101

OBJECTIVE

We sought to validate Risk Equations for Complications of Type 2 Diabetes (RECODe) among diverse populations.

RESEARCH DESIGN AND METHODS

We compared risk predictions from RECODe equations and from two alternative risk models (UK Prospective Diabetes Study Outcomes Model 2 [UKPDS OM2] and American College of Cardiology/American Heart Association Pooled Cohort Equations) to observed outcomes in two studies: the Multi-Ethnic Study of Atherosclerosis (MESA, n = 1,555 adults with type 2 diabetes, median follow-up 9.1 years) and the Jackson Heart Study (JHS, n = 1,746 adults with type 2 diabetes, median follow-up 8.0 years). Outcomes included nephropathy by multiple measures (microalbuminuria, macroalbuminuria, renal failure, end-stage renal disease, and reduction in glomerular filtration rate), moderate to severe diabetic retinopathy by Airlie House classification, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, congestive heart failure, and all-cause mortality.

RESULTS

RECODe equations for microvascular and cardiovascular outcomes had C-statistics for discrimination ranging from 0.71 to 0.85 in MESA and 0.64 to 0.91 in JHS for alternative outcomes. Calibration slopes in MESA ranged from 0.62 for a composite nephropathy outcome, 0.83–1.04 for individual nephropathy outcomes, 1.07 for retinopathy, 1.00–1.05 for cardiovascular outcomes, and 1.03 for all-cause mortality. Slopes in JHS ranged from 0.47 for retinopathy, 0.97–1.16 for nephropathy, 0.72–1.05 for cardiovascular outcomes, and 1.01 for all-cause mortality. The alternative models had C-statistics 0.50–0.72 and calibration slopes 0.07–0.60.

CONCLUSIONS

RECODe equations improved risk estimation for diverse patients with type 2 diabetes, as compared with two commonly used alternatives.

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<![CDATA[Modulation of GLP-1 Levels by a Genetic Variant That Regulates the Cardiovascular Effects of Intensive Glycemic Control in ACCORD]]> https://www.researchpad.co/article/5c6367fed5eed0c484b1af8d

OBJECTIVE

A genome-wide association study in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial identified two markers (rs57922 and rs9299870) that were significantly associated with cardiovascular mortality during intensive glycemic control and could potentially be used, when combined into a genetic risk score (GRS), to identify patients with diabetes likely to derive benefit from intensive control rather than harm. The aim of this study was to gain insights into the pathways involved in the modulatory effect of these variants.

RESEARCH DESIGN AND METHODS

Fasting levels of 65 biomarkers were measured at baseline and at 12 months of follow-up in the ACCORD-Memory in Diabetes (ACCORD-MIND) MRI substudy (n = 562). Using linear regression models, we tested the association of the GRS with baseline and 12-month biomarker levels, and with their difference (Δ), among white subjects, with genotype data (n = 351) stratified by intervention arm.

RESULTS

A significant association was observed between GRS and ΔGLP-1 (glucagon-like peptide 1, active) in the intensive arm (P = 3 × 10−4). This effect was driven by rs57922 (P = 5 × 10−4). C/C homozygotes, who had been found to derive cardiovascular benefits from intensive treatment, showed a 22% increase in GLP-1 levels during follow-up. By contrast, T/T homozygotes, who had been found to experience increased cardiac mortality with intensive treatment, showed a 28% reduction in GLP-1 levels. No association between ΔGLP-1 and GRS or rs57922 was observed in the standard treatment arm.

CONCLUSIONS

Differences in GLP-1 axis activation may mediate the modulatory effect of variant rs57922 on the cardiovascular response to intensive glycemic control. These findings highlight the importance of GLP-1 as a cardioprotective factor.

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<![CDATA[FGF23 Concentration and APOL1 Genotype Are Novel Predictors of Mortality in African Americans With Type 2 Diabetes]]> https://www.researchpad.co/article/5c35441fd5eed0c484d8aa62

OBJECTIVE

Cardiovascular and renal complications contribute to higher mortality in patients with diabetes. We assessed novel and conventional predictors of mortality in African American–Diabetes Heart Study (AA-DHS) participants.

RESEARCH DESIGN AND METHODS

Associations between mortality and subclinical atherosclerosis, urine albumin–to–creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), plasma fibroblast growth factor 23 (FGF23) concentration, African ancestry proportion, and apolipoprotein L1 genotypes (APOL1) were assessed in 513 African Americans with type 2 diabetes; analyses were performed using Cox proportional hazards models.

RESULTS

At baseline, participants were 55.6% female with median (25th, 75th percentile) age 55 years (49.0, 62.0), diabetes duration 8 years (5.0, 13.0), glycosylated hemoglobin 60.7 mmol/mol (48.6, 76.0), eGFR 91.3 mL/min/1.73 m2 (76.4, 111.3), UACR 12.5 mg/mmol (4.2, 51.2), and coronary artery calcium 28.5 mg Ca2+ (1.0, 348.6); 11.5% had two APOL1 renal-risk variants. After 6.6-year follow-up (5.8, 7.5), 54 deaths were recorded. Higher levels of coronary artery calcified plaque, carotid artery calcified plaque, albuminuria, and FGF23 were associated with higher mortality after adjustment for age, sex, and African ancestry proportion. A penalized Cox regression that included all covariates and predictors associated with mortality identified male sex (hazard ratio [HR] 4.17 [95% CI 1.96–9.09]), higher FGF23 (HR 2.10 [95% CI 1.59–2.78]), and absence of APOL1 renal-risk genotypes (HR 0.07 [95% CI 0.01–0.69]) as the strongest predictors of mortality.

CONCLUSIONS

Accounting for conventional risk factors, higher FGF23 concentrations and APOL1 non–renal-risk genotypes associated with higher mortality in African Americans with diabetes. These data add to growing evidence supporting FGF23 association with mortality; mechanisms whereby these novel predictors impact survival remain to be determined.

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