Higher serum bilirubin level as a protective factor for the development of diabetes in healthy Korean men: A 4 year retrospective longitudinal study

Objective

Bilirubin, a natural product of heme catabolism by heme oxygenase, one of key antioxidant enzymes, has been recognized as a substance with potent antioxidant and cytoprotective properties. Several studies have shown a significant negative relationship between serum bilirubin levels and the risk of metabolic disorders, including type 2 diabetes. However, longitudinal studies investigating the association of elevated serum bilirubin levels and type 2 diabetes are lacking. In the present study, we aimed to investigate the longitudinal effects of baseline serum bilirubin concentrations on the development of type 2 diabetes in healthy Korean men.

Materials and Methods

This 4 year retrospective longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 5960 men without type 2 diabetes who underwent routine health examinations in 2007 (baseline) and 2011 (follow-up). Baseline serum bilirubin concentrations were determined by the vanadate oxidation method.

Results

During a 4 year period, 409 incident cases of diabetes (6.9 %) were identified. Incident type 2 diabetes decreased across the baseline bilirubin quartile categories (P for trend < 0.001). In multivariable-adjusted model, the relative risk (RR) for the development of type 2 diabetes was significantly lower in the highest (i.e., 1.30–2.00 mg/dl) than in the lowest bilirubin quartile category (i.e., ≤ 0.90 mg/dl), even after adjustment for confounding variables (RR = 0.69, 95% confidence interval 0.48–0.99, P for trend = 0.041).

Conclusions

The results indicate that serum total bilirubin level may provide additional information for predicting future development of type 2 diabetes in healthy subjects.     

Contribution of very low-density lipoprotein triglyceride fatty acids to postabsorptive free fatty acid flux in obese humans

Objective

In the fasting state, plasma free fatty acids (FFA) are thought to derive almost exclusively from adipose tissue lipolysis. However, there are mixed reports as to whether the spillover of fatty acids (FA) from very low-density lipoprotein triglyceride (VLDL–TG) hydrolysis contributes significantly to the plasma FFA pool. Because substantial VLDL–TG fatty acid spillover into the plasma FFA pool would profoundly impact the interpretation of isotope dilution measures of FFA flux, we investigated the contribution of VLDL–TG spillover to plasma FFA appearance.

Materials/Methods

Eighteen obese adults (15 women) participated in these studies. Each volunteer received a primed, continuous infusion of their own ex-vivo labeled ([1-¹⁴C]triolein) VLDL–TG and a continuous infusion of [U-¹³C]oleate (8 nmol · kg fat free mass^− 1 · min^− 1) to measure VLDL–TG and FFA rate of appearance (Ra), respectively. The presence of ¹⁴C-oleate in the plasma FFA–oleate pool was used to calculate the contribution of spillover from VLDL–TG–oleate to the plasma FFA–oleate Ra.

Results

The spillover rate of VLDL–TG–oleate into plasma FFA–oleate was 6 ± 2 μmol/min (7% ± 2% of [¹⁴C]oleate from VLDL–TG) and FFA–oleate flux was 240 ± 61 μmol/min. Thus, only 3% ± 1% of total plasma FFA–oleate appearance could be accounted for by VLDL–TG spillover.

Conclusion

The contribution of VLDL–TG spillover to the total plasma FFA pool is negligible and will not materially affect the interpretation of FFA flux measures as an index of adipose tissue lipolysis.     

Coffee and green tea consumption is associated with insulin resistance in Japanese adults

Objective

Higher coffee and green tea consumption has been suggested to decrease risk of type 2 diabetes, but their roles in insulin resistance (IR) and insulin secretion remain unclear. This study examined the association between habitual consumption of these beverages and markers of glucose metabolism in a Japanese working population.

Materials/Methods

Participants were 1440 Japanese employees (1151 men and 289 women) aged 18–69 years. Consumption of coffee and green tea was ascertained via a validated brief diet history questionnaire. Multilevel linear regression was used to estimate means (95% confidence intervals) of fasting insulin, fasting plasma glucose, homeostatic model assessment of IR (HOMA-IR), homeostatic model assessment of β-cell function (HOMA-β) and glycated hemoglobin (HbA1c) with adjustment for potential confounding variables.

Results

Coffee consumption was significantly, inversely associated with HOMA-IR (P for trend = 0.03), and the association appeared to be confined to overweight subjects (BMI ≥ 25 kg/m²) (P for trend = 0.01, P for interaction = 0.08). Unexpectedly, green tea consumption was positively associated with HOMA-IR (P for trend = 0.02), though there was no dose–response relationship among daily consumers of green tea. Neither coffee nor green tea consumption was associated with HOMA-β and HbA1c.

Conclusions

Our findings indicate that coffee consumption may be associated with decreased IR, but not with insulin secretion. The positive association between green tea consumption and IR warrants further investigation.     

Acute changes in lipoprotein subclasses during exercise

Objective

Lipids are important substrates for oxidation in the basal fasting state and during exercise. Studies have demonstrated beneficial changes in lipoprotein subclass composition the day after an exercise bout. However, the acute effect of exercise on TG concentration and lipoprotein subclass composition remains unclear.

Materials/Methods

Sixteen lean, healthy individuals (8 men and 8 women) were recruited (age 20–30 years, BMI < 25 kg/m²). The subjects were studied during basal fasting conditions as well as during and after 90 min of cycling at 50% of VO₂peak. Lipoprotein subclass composition was measured with ¹H NMR spectroscopy.

Results

During exercise, LDL and HDL particle concentration increased significantly (p < 0.05) despite lower total TG concentration. In addition, exercise resulted in a shift towards smaller VLDL particles in men (p < 0.05), but VLDL–TG concentration was unaltered.

Conclusions

Acute exercise induces beneficial changes in lipoprotein subclass composition. These changes are similar to the effects of exercise training.     

Eight weeks of treatment with long-acting GLP-1 analog taspoglutide improves postprandial insulin secretion and sensitivity in metformin-treated patients with type 2 diabetes

Objective

Loss of pancreatic function is pivotal to the deterioration of fasting and postprandial glycemic control in type 2 diabetes (T2D). We evaluated the effects of a long-acting, human glucagon-like peptide-1 analog, taspoglutide, added to metformin, on pancreatic function and peripheral insulin sensitivity.

Materials/methods

We studied 80 T2D patients inadequately controlled [glycosylated hemoglobin (HbA_1c), 7.0%–9.5%] receiving stable metformin for ≥ 12 weeks. They were a subset of participants to a phase 2 trial that received also a 240-min mixed-meal tolerance test (MTT) at baseline and study end. Patients received once weekly (QW) sc injection of taspoglutide 5, 10, or 20 mg (n = 21, 19, or 19), or placebo (n = 21), plus metformin, for 8 weeks. We measured postprandial plasma glucose (PPG) and insulin profiles, insulin secretion rate (ISR), oral glucose insulin sensitivity (OGIS) index; β-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios, and insulin sensitivity-to-insulin resistance (or disposition) index.

Results

After 8 weeks of treatment, taspoglutide 5, 10, and 20 mg QW doses vs. placebo improved mean PPG_{0–240 min} (relative change from baseline: − 22.1%, − 25.9%, and − 22.9% vs. − 8.1%; P < 0.005) and mean postprandial ISR_{0–240 min} (+ 14%, + 18%, and + 23% vs. + 1%; P < 0.005 vs dose). Taspoglutide at 20 mg QW dose also resulted in improvements from baseline in OGIS, β-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios and the disposition index during the MTT.

Conclusion

Taspoglutide QW significantly improved pancreatic function in patients with T2D treated with metformin.     

Glucoregulatory function among African Americans and European Americans with normal or pre-diabetic hemoglobin A1c levels

Objective

A hemoglobin (Hb) A1c range of 5.7%–6.4% has been recommended for the diagnosis of prediabetes. To determine the significance of such “prediabetic” HbA1c levels, we compared glucoregulatory function in persons with HbA1c levels of 5.7%–6.4% and those with HbA1c < 5.7%.

Methods

We studied 280 nondiabetic adults (142 black, 138 white; mean (± SD) age 44.2 ± 10.6 years). Each subject underwent clinical assessment, blood sampling for HbA1c measurement, and a 75-g oral glucose tolerance test at baseline. Additional assessments during subsequent outpatient visits included insulin sensitivity, using homeostasis model assessment (HOMA)-IR and the hyperinsulinemic euglycemic clamp; insulin secretion, using HOMA-B and frequently samples intravenous glucose tolerance test (FSIVGTT) and disposition index (DI); and measurement of fat mass, using DXA.

Results

Compared to subjects with HbA1c < 5.7%, persons with HbA1c levels of 5.7%–6.4% were older, and had higher body mass index (BMI) and insulin secretion but similar insulin sensitivity. When the two groups were matched in age and BMI, persons with HbA1c 5.7%–6.4% were indistinguishable from those with HbA1c < 5.7% with regard to all measures of glycemia and glucoregulatory function.

Conclusions

Unlike glucose-defined prediabetes status, an HbA1c range of 5.7%–6.4% does not reliably identify individuals with impaired insulin action or secretion, the classical defects underlying the pathophysiology of prediabetes. Thus, HbA1c cannot validly replace blood glucose measurement in the diagnosis of prediabetes. If utilized as a screening test due to convenience, aberrant HbA1c values should be corroborated with blood glucose measurement before therapeutic intervention.     

Greater impairment of postprandial triacylglycerol than glucose response in metabolic syndrome subjects with fasting hyperglycaemia

Objective

Studies have started to question whether a specific component or combinations of metabolic syndrome (MetS) components may be more important in relation to cardiovascular disease risk. Our aim was to examine the impact of the presence of raised fasting glucose as a MetS component on postprandial lipaemia.

Methods

Men classified with the MetS underwent a sequential test meal investigation, in which blood samples were taken at regular intervals after a test breakfast (t = 0 min) and lunch (t = 330 min). Lipids, glucose and insulin were measured in the fasting and postprandial samples.

Results

MetS subjects with 3 or 4 components were subdivided into those without (n = 34) and with (n = 23) fasting hyperglycaemia (≥ 5.6 mmol/l), irrespective of the combination of components. Fasting lipids and insulin were similar in the two groups, with glucose significantly higher in the men with glucose as a MetS component (P < 0.001). Following the test meals, there were higher maximum concentration (maxC), area under the curve (AUC) and incremental AUC (P ≤ 0.016) for the postprandial triacylglycerol (TAG) response in men with fasting hyperglycaemia. Greater glucose AUC (P < 0.001) and insulin maxC (P = 0.010) were also observed in these individuals after the test meals. Multiple regression analysis revealed fasting glucose to be an important predictor of the postprandial TAG and glucose response.

Conclusion

Our data analysis has revealed a greater impairment of postprandial TAG than glucose response in MetS subjects with raised fasting glucose. The worsening of postprandial lipaemic control may contribute to the greater CVD risk reported in individuals with MetS component combinations which include hyperglycaemia.     

The one year exercise and lifestyle intervention program KLAKS: Effects on anthropometric parameters,cardiometabolic risk factors and glycemic control in childhood obesity

Objective

Regular physical exercise within structured lifestyle programs may improve weight status and minimize metabolic risk factors in childhood obesity. The aim of this study was to evaluate the effect of the one-year combined physical exercise/lifestyle program KLAKS on anthropometric and metabolic parameters and glycemic control in childhood obesity.

Materials and Methods

142 overweight/obese (BMI > 90th percentile) candidates (7–18 years) were enrolled, 115 participants completed the program. Anthropometrics and biochemical parameters were obtained at beginning and completion. An oral glucose tolerance test (OGTT) was performed in a subgroup of participants. Course of glucose and insulin levels within OGTT was correlated with several parameters and is reported here for those who completed the program.

Results

The mean standard deviation scores (SDS) decreased significantly for BMI, waist circumference, waist-to-height ratio (WHtR) and percentage body fat (all p ≤ 0.01). Improved metabolic risk markers included mean glucose levels within an OGTT at follow-up compared to baseline (p < 0.0001) and HbA1c (p = 0.05) as well as indications of improvement for gamma-glutamyl-transferase and free fatty acids.

Conclusions

The one-year combined exercise/lifestyle program KLAKS significantly improves markers of obesity and glycemic control. Impaired cardiometabolic risk markers, even subclinical, are also favorably influenced by program participation.     

Effect of Renin–Angiotensin System Inhibition on Cardiovascular Events in Older Hypertensive Patients with Metabolic Syndrome

Objective

Metabolic syndrome (MetS) is associated with cardiovascular disease (CVD). Insulin resistance has been hypothesized as the underlying feature of MetS. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are widely used antihypertensives that may improve insulin sensitivity. The aim of the study is to evaluate the effect of ACEI/ARB on incident CVD events in older hypertensive patients with MetS.

Materials/Methods

We used the Cardiovascular Health Study, a prospective cohort study of individuals > 65 years of age to evaluate ACEI/ARB use and time to CVD events (including coronary and cerebrovascular events). The study included 777 subjects who had hypertension and ATP III-defined MetS, but free of CVD and diabetes at baseline. Cox regression models were used to evaluate the effect of ACEI/ARB as compared to other antihypertensives on the time to the first CVD events.

Results

ACEI/ARB use was associated with a decreased risk of CVD events (adjusted HR = 0.658, 95 % C.I. [0.436–0.993]) compared to other antihypertensives. When CVD endpoints were evaluated separately, use of ACEI/ARB was associated with lower rates of angioplasty and coronary events (HR of 0.129 and 0.530 respectively, with 95 % CI [0.017–0.952] and [0.321–0.875]).

Conclusions

ACEI/ARB use was associated with a lower risk of CVD events in older hypertensive patients with MetS, primarily due to a reduction in coronary events. The potential protective effect of ACEI/ARB on CVD events in older individuals with MetS will need further confirmation from prospective studies.     

Low serum bilirubin concentration is a novel risk factor for the development of albuminuria in patients with type 2 diabetes

Objective

Bilirubin has been recognized as an important endogeneous antioxidant. Previous studies reported that bilirubin could prevent atherosclerosis. The aim of this study was to investigate if serum bilirubin concentration could be a predictor for the development of albuminuria in patients with type 2 diabetes.

Materials and Methods

We measured serum bilirubin in 320 consecutive patients with normoalbuminuria. We performed follow-up study to assess the development of albuminuria, mean interval of which was 3.2 ± 0.9 years. Cox proportional hazards regression was used to examine the relationship between serum bilirubin concentration and the development of albuminuria.

Results

During follow-up duration, 43 patients have developed albuminuria. In multivariate analysis, after adjusting for comprehensive risk factors, the risk of developing albuminuria was higher in the lowest quartile of serum bilirubin concentrations than that in the highest quartile of serum bilirubin concentrations (Hazard ratio, 5.76; 95% CI, 1.65 to 24.93).

Conclusions

Low serum bilirubin concentration could be a novel risk factor for the development of albuminuria in patients with type 2 diabetes.     

Association between fasting serum glucose levels and incidence of colorectal cancer in Korean men: The Korean Cancer Prevention Study-II

Introduction

The incidence of colorectal cancer (CRC) is steadily increasing worldwide. Numerous studies have demonstrated that diabetes mellitus is related to an increased risk of CRC; however, the association between impaired fasting glucose and CRC is unclear. Therefore, we evaluated the correlation between fasting serum glucose (FSG) levels and the incidence of CRC, which can be used to develop novel methods for preventing CRC.

Methods

A total of 175,677 individuals from the Korean Metabolic Syndrome Research Initiative study were enrolled between 2004 and 2011. The incidence of CRC was assessed during a mean follow-up of 4.7 years. Hazard ratios (HR) for CRC according to FSG levels were calculated with the Cox proportional hazard model adjusted for age, sex, body mass index, smoking status, alcohol consumption, and regular exercise.

Results

The risk of developing CRC in subjects with high FSG was significant (HR, 1.45; 95% confidence interval [CI], 1.10–1.90), and the risk was higher in men (HR, 1.51; 95% CI, 1.12–2.05). The HR of rectal cancer, but not colon cancer, was significantly higher both in the total population and in men in the high FSG group.

Conclusions

The incidence of CRC positively correlated with FSG levels in men. Rectal cancer incidence was especially correlated with high FSG in the site-specific analysis. Therefore, serum glucose levels maybe a potential marker of colorectal cancer. Early detection and intervention for controlling elevated glucose levels may be indicated as a way to prevent carcinogenesis.     

Association of computed tomography-derived left atrial size with major cardiovascular events in the general population: The Heinz Nixdorf Recall Study

Background

Echocardiography based data suggests that left atrial (LA) size is associated with cardiovascular morbidity and mortality. Once non-contrast cardiac CT is performed for prevention purposes, information on the LA is readily available. We aimed to determine whether LA area from non-contrast cardiac CT is associated with incident major cardiovascular (CV) events, independent of CV risk factors and coronary artery calcium (CAC), based on a general population cohort.

Methods

Subjects aged 45–75 years without prevalent CV disease from the population-based Heinz Nixdorf Recall Study were enrolled between 2000 and 2003. LA area at the level of the mitral valve was quantified from non-contrast cardiac CT. Major CV events (coronary event, stroke, CV death) were assessed during follow-up. The association of LA with events was assessed using Cox regression analysis.

Results

Overall, 3958 subjects (59.2 ± 7.7 years, 53% female) were included. Mean LA area was 17.64 ± 4.22 cm² (range: 7.16–44.13 cm²). During 8.0 ± 1.5 years of follow-up, 221 major CV events occurred. In univariate analysis, increase of LA size by 1 standard deviation was associated with nearly 50% excess events (HR (95%CI): 1.48 (1.32–1.65)), which remained significant after adjustment for CV risk factors (HR (95%CI): 1.25 (1.09–1.43)) and when additionally adjusting for CAC (HR (95%CI): 1.22 (1.07–1.40)). Associations for LA size were similar for each endpoint and again independent of risk factors and CAC (coronary event: HR (95%CI): 1.21 (1.01–1.45); stroke: 1.31 (1.05–1.63); CV death: 1.33 (1.03–1.71)).

Conclusion

LA size is associated with incident major CV events independent of risk factors and CAC-score. Once cardiac CT imaging is performed, assessment of LA size may complement information of this imaging modality.     

Gender and body mass index modify the effect of increasing amounts of caffeinated coffee on postprandial glucose and insulin concentrations; a randomized,controlled, clinical trial

Objective

To examine the effects of different coffee amounts on blood glucose and insulin concentrations of healthy volunteers, and to assess potential effect modification by sex and body mass index category.

Materials/Methods

Thirty-three volunteers [16♀/17♂, 16 normal-weight and 17 overweight/obese, 27.3 ± 7.2 (19–44) y] took part in this randomized, crossover study. Ιn the morning of each experimental day volunteers received a standardized meal along with 200 mL of water or instant coffee containing either 3 or 6 mg of caffeine/kg body weight. Blood samples were obtained and analyzed for glucose and insulin concentrations in the fasting state, immediately after meal/drink consumption and at standard time points for the next 3 h thereafter.

Results

Coffee delayed the rise of insulin in response to the standardized meal and the fall of glucose concentrations from its maximum levels in the entire study sample. Glucose incremental area under the curve (IAUC) was significantly different between interventions (P = .009) with both coffee amounts inducing a greater area compared to water. Secondary, subgroup analysis at the nominal level showed that this might be more evident among females (P_IAUC = .05) and overweight/obese participants (P_IAUC = .03). Furthermore, coffee, mainly the 6 mg dose, could be lowering insulin concentrations the first 30 min after its consumption compared to water in men and overweight/obese participants.

Conclusions

Coffee exerts an acute effect on postprandial glucose and insulin concentrations. This effect may be modified by sex and overweight/obese status. Future research is necessary to elucidate underlying mechanisms.     

Trajectories of the Framingham general cardiovascular risk profile in midlife and poor motor function later in life: The Whitehall II study

Background

Vascular risk factors are associated with increased risk of cognitive impairment and dementia, but their association with motor function, another key feature of aging, has received little research attention. We examined the association between trajectories of the Framingham general cardiovascular disease risk score (FRS) over midlife and motor function later in life.

Methods

A total of 5376 participants of the Whitehall II cohort study (29% women) who had up to four repeat measures of FRS between 1991–1993 (mean age = 48.6 years) and 2007–2009 (mean age = 65.4 years) and without history of stroke or coronary heart disease in 2007–2009 were included. Motor function was assessed in 2007–2009 through objective tests (walking speed, chair rises, balance, finger tapping, grip strength). We used age- and sex-adjusted linear mixed models.

Results

Participants with poorer performances for walking speed, chair rises, and balance in 2007–2009 had higher FRS concurrently and also in 1991–1993, on average 16 years earlier. These associations were robust to adjustment for cognition, socio-economic status, height, and BMI, and not explained by incident mobility limitation prior to motor assessment. No association was found with finger tapping and grip strength.

Conclusions

Cardiovascular risk early in midlife is associated with poor motor performances later in life. Vascular risk factors play an important and under-recognized role in motor function, independently of their impact on cognition, and suggest that better control of vascular risk factors in midlife may prevent physical impairment and disability in the elderly.     

Prolonged sitting and markers of cardiometabolic disease risk in children and youth: A randomized crossover study

Objective

Recent evidence suggests that short bouts of uninterrupted sedentary behavior reduce insulin sensitivity and glucose tolerance while increasing triglyceride levels in both healthy and overweight/obese adults. To date no study has examined the acute impact of uninterrupted sitting in children and youth. The objective of the present study was to determine whether 8 h of uninterrupted sitting increases markers of cardiometabolic disease risk in healthy children and youth, in comparison to 8 h of sitting interrupted by light intensity walk breaks or structured physical activity.

Materials/Methods

11 healthy males and 8 healthy females between the ages of 10 and 14 years experienced 3 conditions in random order: (1) 8 h of uninterrupted sitting (Sedentary); (2) 8 h of sitting interrupted with a 2-min light-intensity walk break every 20 min (Breaks); and (3) 8 h of sitting interrupted with a 2-min light-intensity walk break every 20 min as well as 2 × 20 min of moderate-intensity physical activity (Breaks + Physical Activity). Insulin, glucose, triglyceride, HDL and LDL cholesterol area under the curve were calculated for each condition.

Results

We observed no significant differences in the area under the curve for any marker of cardiometabolic disease risk across the 3 study conditions (all p > 0.09).

Conclusions

These results suggest that in comparison to interrupted sitting or structured physical activity, a single bout of 8 h of uninterrupted sitting does not result in measurable changes in circulating levels of insulin, glucose, or lipids in healthy children and youth.     

Lactation intensity and fasting plasma lipids,lipoproteins, non-esterified free fatty acids,leptin and adiponectin in postpartum women with recent gestational diabetes mellitus: The SWIFT cohort

Objectives

Lactation may influence future progression to type 2 diabetes after gestational diabetes mellitus (GDM). However, biomarkers associated with progression to glucose intolerance have not been examined in relation to lactation intensity among postpartum women with previous GDM. This study investigates whether higher lactation intensity is related to more favorable blood lipids, lipoproteins and adipokines after GDM pregnancy independent of obesity, socio-demographics and insulin resistance.

Methods

The Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT) is a prospective cohort study that recruited 1035 women diagnosed with GDM by the 3-h 100 g oral glucose tolerance tests (OGTTs) after delivery of a live birth in 2008–2011. Research staff conducted 2-h 75 g OGTTs, and assessed lactation intensity, anthropometry, lifestyle behaviors and socio-demographics at 6–9 weeks postpartum (baseline). We assayed fasting plasma lipids, lipoproteins, non-esterified free fatty acids, leptin and adiponectin from stored samples obtained at 6–9 weeks postpartum in 1007 of the SWIFT participants who were free of diabetes at baseline. Mean biomarker concentrations were compared among lactation intensity groups using multivariable linear regression models.

Results

Increasing lactation intensity showed graded monotonic associations with fully adjusted mean biomarkers: 5%–8% higher high-density lipoprotein cholesterol (HDL-cholesterol), 20%–28% lower fasting triglycerides, 15%–21% lower leptin (all trend P-values < 0.01), and with 6% lower adiponectin, but only after adjustment for insulin resistance (trend P-value = 0.04).

Conclusion

Higher lactation intensity was associated with more favorable biomarkers for type 2 diabetes, except for lower plasma adiponectin, after GDM delivery. Long-term follow-up studies are needed to assess whether these effects of lactation persist to predict progression to glucose intolerance.     

Elevated plasma fractalkine levels are associated with higher levels of IL-6, Apo-B,LDL-C and insulin,but not with body composition in a large female twin sample

Objective

Plasma fractalkine (FRACT) is involved in the development of numerous inflammatory conditions including atherosclerosis. It is associated with type 2 diabetes mellitus and adipose inflammation. However, whether FRACT is associated with major risk factors for cardiovascular disease, in particular obesity, metabolic syndrome and blood lipids, is virtually unknown.

Methods

The study included a large community-based sample of 3306 middle-aged women drawn from the general UK population. Blood samples were analyzed for circulating levels of FRACT, leptin, insulin, glucose, LDL-C, HDL-C, Apo-A, ApoB and IL-6. Obesity was assessed by fat body mass (FBM) using dual-energy x-ray absorptiometry and by body mass index (BMI).

Results

We found no association between FRACT and body composition, in particular adiposity. Obese and non obese subjects with metabolic syndrome tended to have higher levels of FRACT compared with non-obese subjects without metabolic syndrome but this did not reach statistical significance. Most importantly we report significant correlations between FRACT and circulating IL-6, Apo-B, LDL-C and insulin. The associations with IL-6 and Apo-B were particularly significant (P-value < 0.001), and survived correction for multiple testing and adjustment for age and other covariates.

Conclusion

Higher FRACT levels correlated with elevated levels of IL-6, Apo-B, LDL-C and insulin, all known risk factors for several clinical related diseases suggesting a potential role of FRACT in inflammation and tissue injury. Variations of FRACT levels are not influenced by body composition and are not correlated with leptin indicating that fat mass alone is not responsible for elevation of FRACT seen in obese individuals.     

Vildagliptin compared to glimepiride on post-prandial lipemia and on insulin resistance in type 2 diabetic patients

Objectives

To evaluate the effects of vildagliptin compared to glimepiride on glycemic control, insulin resistance and post-prandial lipemia.

Material and Methods

167 type 2 diabetic patients, not adequately controlled by metformin, were randomized to vildagliptin 50 mg twice a day or glimepiride 2 mg three times a day for 6 months, in a double blind, randomized clinical trial. We evaluated: body mass index (BMI), glycemic control, fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), fasting plasma proinsulin (FPPr), glucagon, lipid profile, resistin, retinol binding protein-4 (RBP-4), visfatin and vaspin. Furthermore, at the randomization and at the end of the study all patients underwent an euglycemic hyperinsulinemic clamp to evaluate M value and an oral fat load.

Results

Despite a similar decrease of glycated hemoglobin, there were an increase of body weight with glimepiride + metformin and a decrease with vildagliptin + metformin. Fasting plasma insulin increased with glimepiride + metformin, while it did not change with vildagliptin + metformin. Vildagliptin + metformin improved lipid profile. Regarding insulin sensitivity, vildagliptin + metformin increased M value. Resistin, RBP-4, vaspin and visfatin were decreased by vildagliptin + metformin, but in group to group comparison, only vaspin reduction resulted statistically significant. Vildagliptin + metformin reduced post-prandial lipemia and insulinemia compared to glimepiride + metformin.

Conclusion

Vildagliptin, in addition to metformin, was more effective than glimepiride + metformin in reducing insulin resistance and post-prandial lipemia.     

Serum levels of soluble receptor for advanced glycation end-products and metabolic syndrome: The Northern Manhattan Study

Objective

Recent studies have shown a strong link between serum soluble receptor for advanced glycation end-products (sRAGE) levels and cardiovascular risk factors and disease. What is less clear is the relationship between metabolic risk factors and sRAGE levels. Here, we tested the hypothesis that lower sRAGE levels may be associated with the metabolic syndrome (MetS) in an urban multi ethnic population.

Materials/methods

From the Northern Manhattan Study (NOMAS), we included 1101 stroke-free participants (mean age: 71 ± 9 years, 60% women, 64% Hispanic, 18% black, 16% white). Serum sRAGE was measured by ELISA. Quantile regression analysis was performed to evaluate the association between sRAGE and MetS components and MetS, after adjusting for sociodemographics, smoking status and kidney function.

Results

The median (interquartile) sRAGE was 899 pg/ml (647–1248 pg/ml), 42% had metabolic syndrome. The prevalence of unfavorable metabolic factors was 50% for waist circumference (WC), 81% for blood pressure, 39% for fasting glucose, 35% for reduced high density lipoproteins (HDL), and 23% for triglycerides. After adjustment, the median sRAGE levels were at least 120 pg/ml lower in those who had elevated WC (p < 0.0001), blood pressure (p = 0.0014), and fasting glucose (p < 0.0001), and those who had 2 or more unfavorable metabolic factors. No relationship was seen between sRAGE levels and elevated triglycerides or reduced HDL levels. Interaction and stratified analyses revealed that the association of sRAGE with MetS was more prominent in Hispanics compared to whites, and displaying no association with components of MetS in blacks.

Conclusions

sRAGE levels were mainly associated with MetS factors related to obesity, diabetes and hypertension, and displayed variation with ethnicity in a multi-ethnic population. Further studies of sRAGE, MetS and their relationship to cardiovascular disease are warranted.     

Effects of exercise on C-reactive protein,inflammatory cytokine and adipokine in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

Objective

C-reactive protein (CRP), inflammatory cytokines, and adipokines contribute to atherosclerosis, insulin resistance, and development of late-onset complication in patients with type 2 diabetes. We performed a systematic review to assess effects of exercise interventions on inflammatory markers/cytokines and adipokines.

Materials/Methods

We searched electronic databases (MEDLINE, EMBASE, and Cochrane Controlled Trials Registry) and reference lists in relevant papers for articles published in 1966–2013. We selected studies that evaluated the effects of exercise intervention on inflammatory markers/cytokines and adipokines in adult patients with type 2 diabetes. Weighted mean differences of exercise on outcomes were derived using fixed or random effect models; factors influencing heterogeneity were identified using meta-regression analysis.

Results

Fourteen randomized controlled trials (824 patients) were included in our meta-analysis. Exercise was associated with a significant in CRP = − 0.66 mg/l (95% CI, − 1.09 to − 0.23 mg/l; − 14% from baseline) and interleukin-6 (IL-6) = − 0.88 pg/ml (95% CI, − 1.44 to − 0.32 pg/ml; − 18% from baseline) but did not alter adiponectin or resistin levels; aerobic exercise program was associated with a significant change in leptin = − 3.72 ng/ml (95% CI, − 6.26 to − 1.18 ng/ml; − 24% from baseline). For IL-6, exercise was more effective in those with a longer duration in the program and larger number of sessions during study (p = 0.001).

Conclusions

Exercise decreases inflammatory cytokine (CRP and IL-6) in patients with type 2 diabetes. Exercise could be a therapeutic option for improving abnormalities in inflammation levels in patients with diabetes.