Efficacy of the Glucagon-Like Peptide-1 Receptor Agonists Liraglutide and Semaglutide for the Treatment of Weight Regain After Bariatric surgery: a Retrospective Observational Study.

PURPOSE: Weight regain after bariatric surgery occurs in up to a third of patients and reduces treatment-associated health benefits. The efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RA) for treatment of type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains to be defined. MATERIALS AND METHODS: This was a single centre retrospective observational study conducted at a Swiss bariatric reference centre. Patients with 6 months of treatment with GLP1-RA, up until November 2021, due to weight regain after bariatric surgery were identified. Data on body weight and relevant clinical parameters were collected before and after 6 months of treatment with GLP1-RA. Data are presented as median (interquartile range). RESULTS: Fifty patients (82% female) were included. Before GLP1-RA treatment (liraglutide, n=29; semaglutide, n=21), weight and BMI were 90.5 kg (83.4, 107.9) and 34.0 kg/m2 (31.7, 38.7), respectively, with a post-bariatric weight regain of 15.1% (10.6, 22.8) of total body weight and 4.6 kg/m2 (3.3, 6.2). After 6 months of GLP1-RA treatment, a reduction in weight and BMI of 8.8% (5.2, 11.4) of total body weight and 2.9 kg/m2 (1.8, 4.0) was observed (P value <0.0001), corresponding to 67.4% (40.4, 92.2) of the weight regain. No serious adverse events were reported. CONCLUSION: For patients experiencing weight regain after bariatric surgery, two-thirds of the weight regain can be safely lost with GLP1-RA, providing clinicians with a therapeutic option for this clinical challenge, and highlights the need for a large-scale randomized clinical trial.

High Risk of Hypophosphatemia in Patients with Previous Bariatric Surgery Receiving Ferric Carboxymaltose: A Prospective Cohort Study.

BACKGROUND: Iron deficiency is a common finding in patients with previous bariatric surgery, and parenteral supplementation is frequently required. Ferric carboxymaltose (FCM) is among the preferred compounds used but may be associated with new-onset hypophosphatemia. This study was undertaken to study the prevalence of hypophosphatemia following FCM in patients with previous bariatric surgery, a population that may be at particular risk due to highly prevalent secondary hyperparathyroidism. METHODS: Patients with previous bariatric surgery and iron depletion scheduled for FCM infusion were prospectively studied before and one week after FCM application. The primary endpoint was new-onset hypophosphatemia. Patients were followed until plasma phosphate had normalized without replacement. RESULTS: Fifty-two patients (40 females) following Roux-en-Y gastric bypass (n = 50) or sleeve gastrectomy (n = 2), with a median age of 46 years (range 22-68) and a BMI of 32.2 kg/m2 (27.5-37.3), were analyzed. Fifteen patients (29%) developed new-onset hypophosphatemia, with 11 (21%) requiring oral phosphate supplementation for a median duration of 14 days (14-25). The plasma phosphate decreased by 0.3 mmol/l (-0.5--0.2; p < 0.001) secondary to a 56% increase in the fractional urinary phosphate excretion (p < 0.001). This was associated with a significant increase in serum intact FGF23 (+30%; p < 0.001) and a decrease in serum 1,25(OH)2 vitamin D3 concentrations (-37.6%; p < 0.001). CONCLUSION: Patients with previous bariatric surgery receiving FCM are at considerable risk of developing significant hypophosphatemia secondary to increased renal phosphate wasting through a mechanism involving FGF23. Monitoring plasma phosphate should be considered following FCM in patients with previous bariatric surgery. CLINICAL TRIAL REGISTRATION: ISRCTN registry, ISRCTN12291677, https://www.isrctn.com.

Linear stapled gastrojejunostomy results in fewer strictures compared to circular stapled gastrojejunostomy in laparoscopic gastric bypass surgery.

PURPOSE: Currently, there are two laparoscopic stapling techniques to perform the gastrojejunostomy in gastric bypass surgery: the linear stapling and circular stapling techniques. The aim of the study was to compare the two techniques regarding postoperative morbidity and weight loss at an accredited bariatric reference center in Switzerland. METHODS: We compared two consecutive cohorts at a single institution between November 2012 and June 2014 undergoing laparoscopic gastric bypass surgery. The frequency of complications and weight loss at 1 year was assessed in 109 patients with the 21-mm circular stapling technique (CSA) and 134 patients with the linear stapling technique (LSA). RESULTS: Postoperative complications were more frequent in the CSA group with 23.9 versus 4.5% in the LSA group (p = <0.0001). The main difference was the frequency of strictures, which occurred in 15.6% in the CSA group versus 0% in the LSA group. As a result, endoscopic dilation was required at least once in 15 patients. There was no statistically significant difference in percentage of excessive weight loss (EWL) in both groups; EWL was 74% in the CSA group and 73% in the LSA group (p = 0.68). CONCLUSION: Linear stapled laparoscopic gastric bypass had fewer stenotic strictures with similar weight loss at 1 year compared to circular stapling technique.

Eccentric endurance exercise economically improves metabolic and inflammatory risk factors.

INTRODUCTION: Exercise is a cornerstone of cardiovascular prevention. Because many individuals are not willing or not able to perform regular exercise, new methods of exercise (like eccentric exercise) are necessary. Eccentric endurance exercise is supposed to be less strenuous than concentric exercise but its effects on glucose and lipid metabolism in relation to energy expenditure are unclear. METHODS: We randomly allocated 45 healthy sedentary individuals to one of two groups, each hiking upwards or downwards for 2 months, with a crossover for a further 2 months; for the opposite way, a cable car was used. The difference in altitude was 540 metres; the distance was covered between three and five times a week. Energy expenditure was assessed for each hiking period. RESULTS: Both eccentric and concentric endurance exercise improved glucose tolerance vs. baseline (by 4.1%, p = 0.136; 6.2%, p = 0.023, respectively). Of note, adjustment for energy expenditure per exercise unit (127 ± 22 kcal/unit with eccentric and 442 ± 78 kcal/unit with concentric exercise) revealed a significantly greater improvement of glucose tolerance per kilocalorie spent by eccentric than by concentric exercise (4-times more economical; 0.1123 mg h/dl/kcal vs. 0.0245 mg h/dl/kcal; p = 0.038). Also the decrease of low-density lipoprotein (LDL) cholesterol per kilocalorie spent was significantly stronger with eccentric exercise (0.0982 mg/dl/kcal vs. 0.0346 mg/dl/kcal, p = 0.014). Serum levels of C-reactive protein and creatine kinase activity were reduced in both groups. CONCLUSION: Eccentric endurance exercise economically improves glucose tolerance and LDL cholesterol. It therefore is a promising new exercise modality for individuals who are not able to participate in more strenuous exercise regimens.

Diabetes as a coronary artery disease risk equivalent: before a change of paradigm?

BACKGROUND: Current guidelines consider diabetes per se as a coronary artery disease (CAD) risk equivalent. We aimed at investigating the contribution of baseline coronary atherosclerosis to the risk of diabetic patients for future vascular events. DESIGN: Prospective cohort study. METHODS: Vascular events were recorded over 4 years in 750 consecutive patients undergoing coronary angiography for the evaluation of stable CAD. RESULTS: From our patients, 244 had neither type 2 diabetes (T2DM) nor significant CAD (i.e. coronary stenoses >or=50%) at the baseline angiography, 50 had T2DM but not significant CAD, 342 did not have T2DM but had significant CAD, and 114 had both T2DM and significant CAD. Nondiabetic patients without significant CAD had an event rate of 9.0%. The event rate was similar in T2DM patients without significant CAD (8.0%, P = 0.951), but higher in nondiabetic patients with significant CAD (24.9%, P<0.001). Patients with T2DM and significant CAD had the highest event rate (43.0%). Importantly, T2DM patients without significant CAD had a significantly lower event rate than nondiabetic patients with significant CAD (P = 0.008). CONCLUSION: T2DM per se is not a CAD risk equivalent. Moderate-risk diabetic patients without significant CAD and very high-risk diabetic patients with significant CAD add up to a grand total of high-risk diabetic patients, this is why diabetes seems to be a CAD risk equivalent in many epidemiological studies.

Factors predicting cardiovascular events in statin-treated diabetic and non-diabetic patients with coronary atherosclerosis.

OBJECTIVE: We aimed at identifying which lipid factors drive vascular risk in statin-treated patients with coronary artery disease (CAD). METHODS: We recorded vascular events over 5.6 years in 491 consecutive statin-treated patients with angiographically proven stable CAD, covering 2750 patient-years. RESULTS: In the total population, low high-density lipoprotein (HDL) cholesterol (standardized adjusted HR 0.73 [0.60-0.89]; p=0.001), low apolipoprotein A1 (0.77 [0.65-0.92]; p=0.003), a small low-density lipoprotein (LDL) particle diameter (0.76 [0.64-0.91]; p=0.002), and high triglycerides (1.20 [1.05-1.38]; p=0.007) predicted vascular events, but not total cholesterol, LDL cholesterol, or apolipoprotein B. Factor analysis in the lipid profiles of our patients revealed an HDL-related factor and an LDL-related factor. Concordant with the results for individual lipid parameters, the HDL-related factor (0.69 [0.58-0.83]; p<0.001) but not the LDL-related factor (p=0.455) predicted vascular events. Patients with type 2 diabetes (T2DM; n=116) were at a higher vascular risk than non-diabetic subjects (38.6% vs. 24.1%; p<0.001), and like in the total population the HDL-related factor (0.59 [0.44-0.77]; p<0.001) but not the LDL-related factor (p=0.591) predicted vascular risk in diabetic patients. CONCLUSIONS: The pattern of low HDL cholesterol, low apolipoprotein A1, small LDL particles, and high triglycerides drives vascular risk in statin-treated coronary patients, particularly in those with T2DM.

Type 2 diabetes but not coronary atherosclerosis is an independent determinant of impaired mobility in angiographied coronary patients.

AIMS: We aimed at determining the associations of type 2 diabetes (T2DM) and of angiographically determined coronary artery disease (CAD) with impaired mobility. METHODS: We enrolled 747 consecutive patients undergoing coronary angiography for the evaluation of stable CAD. Mobility was assessed by the standardized timed-up-and-go (TUG) test, a functional test of physical performance. RESULTS: Mobility was impaired (TUG time >10s) in 199 (26.6%) patients. The proportion of subjects with impaired mobility was higher among patients with T2DM than among non-diabetic individuals (40.2% vs. 22.0%; p<0.001), whereas it did not differ significantly between patients with significant coronary stenoses >or=50% and those without such lesions (p=0.802). Multivariate adjustment in logistic regression analyses confirmed that T2DM (adjusted odds ratio (OR)=2.05 [95% CI 1.35-3.11]; p=0.001) but not the presence of significant coronary stenoses (adjusted OR=0.81 [0.55-1.21]; p=0.306) was independently associated with impaired mobility. CONCLUSIONS: T2DM but not coronary atherosclerosis is an independent determinant of impaired mobility in the high risk population of angiographied coronary patients. Mobility enhancing exercise programs are needed for diabetic coronary patients.

Alanine aminotransferase and gamma-glutamyl transferase are associated with the metabolic syndrome but not with angiographically determined coronary atherosclerosis.

BACKGROUND: Recently, elevated liver enzymes have attracted great interest as potential novel markers of cardiovascular risk. Their association with angiographically determined coronary artery disease (CAD) is unknown. METHODS: We enrolled 1000 consecutive patients undergoing coronary angiography for the evaluation of suspected or established stable CAD. The metabolic syndrome (MetS) was defined according to ATP-III criteria; significant CAD was diagnosed in the presence of coronary stenoses with lumen narrowing >or=50%. RESULTS: Serum alanine aminotransferase (ALT), the ALT/aspartate aminotransferase (AST) ratio, and serum gamma-glutamyl transferase (GGT) were significantly higher in patients with the MetS than in subjects without the MetS (34+/-21 vs. 29+/-20 U/l; p<0.001, 1.16+/-0.39 vs. 1.00+/-0.36 U/l, p<0.001; and 53+/-88 vs. 43+/-57 U/l, p=0.001, respectively) but were similar in patients with significant CAD as in those who did not have significant CAD at angiography (p=0.592; p=0.731, and p=0.716, respectively). Analysis of covariance after multivariate adjustment including alcohol consumption confirmed that ALT, ALT/AST ratio, and GGT were significantly and independently associated with the MetS but not with significant CAD. CONCLUSIONS: ALT, the ALT/AST ratio, and GGT are associated with the MetS but not with angiographically determined coronary atherosclerosis.

Type 2 diabetes significantly modulates the cardiovascular risk conferred by the PAI-1 -675 4G/5G polymorphism in angiographied coronary patients.

BACKGROUND: The association of the -675 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene with cardiovascular disease in patients with type 2 diabetes (T2DM) is unknown. METHODS: Genotyping was performed in 672 consecutive Caucasian patients undergoing coronary angiography for the evaluation of stable coronary artery disease (CAD). Vascular events were recorded over 4 years. RESULTS: In non-diabetic subjects (n=524), the homozygous PAI-1 4G4G genotype was significantly associated with significant coronary stenoses>or=50% (adjusted odds ratio (OR) OR=1.84 [1.17-2.92]; p=0.009); however, in T2DM patients (n=148) no such association was observed (OR=0.67 [0.26-1.71]; p=0.401). An interaction term T2DMx4G4G genotype was significant (p=0.006), indicating a significantly stronger association of the polymorphism with CAD in non-diabetic subjects than in patients with T2DM. Also prospectively, the 4G4G genotype conferred an increased risk of vascular events in non-diabetic subjects but not in T2DM patients (hazard ratios 1.76 [1.13-2.74]; p=0.014 and 0.68 [0.30-1.54]; p=0.360, respectively). Again, the interaction T2DMx4G4G genotype was significant (p=0.018). CONCLUSIONS: Presence of T2DM significantly modulates the vascular risk conferred by the PAI-1 -675 4G/5G polymorphism in angiographied coronary patients.

Key role of postchallenge hyperglycemia for the presence and extent of coronary atherosclerosis: an angiographic study.

BACKGROUND: The associations between impaired glucose tolerance (IGT) and postchallenge diabetes with the presence and extent of angiographically characterized coronary atherosclerosis are unclear. MATERIALS AND METHODS: We enrolled 1040 consecutive Caucasian patients undergoing coronary angiography for the evaluation of coronary artery disease (CAD). An oral 75-g glucose tolerance test was performed in patients without previously diagnosed diabetes. RESULTS: From our patients, 394 had normal glucose tolerance (NGT), 190 impaired glucose tolerance (IGT), 90 isolated postchallenge diabetes (postchallenge glucose >or=200 mg/dl), and 366 type 2 diabetes previously established or newly diagnosed on the basis of fasting glucose (conventional diabetes). Coronary atherosclerosis was more frequent in patients with IGT, isolated postchallenge diabetes, or conventional diabetes when compared to NGT subjects (87.9, 95.6, 89.1 versus 80.7%; p=0.030, 0.001, 0.043, respectively). The prevalence of significant coronary stenoses >or=50%, compared to NGT subjects (57.4%), was similar in IGT patients (59.5%; p=0.628), but significantly higher in patients with isolated postchallenge diabetes (77.8%; p=0.001) or conventional diabetes (68.0%; p=0.002). Also the number of significant stenoses compared to NGT subjects was similar in IGT patients, but significantly higher in those with isolated postchallenge or conventional diabetes. These results were confirmed after multivariate adjustment. CONCLUSIONS: Abnormal glucose tolerance is strongly and independently associated with angiographically characterized coronary atherosclerosis. In IGT, non-significant coronary atherosclerosis is more frequent than in NGT; the prevalence and number of significant stenoses increases when postchallenge diabetes evolves.

Relationship between the adipose-tissue hormone resistin and coronary artery disease.

BACKGROUND: Data on the cardiovascular risk associated with the adipose-tissue-related hormone resistin are scarce. METHODS: We measured serum resistin and established vascular risk factors in 547 consecutive patients (age 63+/-10 years) undergoing coronary angiography for the evaluation of stable coronary artery disease. Prospectively, we recorded major coronary events and cumulative vascular events over 4 years. RESULTS: 60% of our patients had significant coronary stenoses with a lumen narrowing > or =50%. Serum resistin was moderately but significantly correlated with age (r=0.139; p=0.001), high-sensitivity C-reactive protein (hsCRP; r=0.228; p<0.001) and decreasing renal function (r=0.240; p<0.001). However, there was no significant difference of serum resistin between patients with CAD and those in whom angiography did not show CAD (4.5 [3.1-5.8] vs. 4.3 [3.4-5.3] ng/ml; p=0.545) and between patients with > or =50% coronary narrowings and those without such lesions (4.5 [3.2-5.9] vs. 4.3 [3.1-5.5] ng/ml; p=0.265). Prospectively, Cox regression analyses neither indicated an association between serum resistin and major coronary events nor between serum resistin and cumulative vascular events. CONCLUSIONS: Among coronary patients serum resistin is significantly correlated with hsCRP, age and decreasing renal function but resistin is neither associated with the presence of significant coronary stenoses nor with the incidence of future vascular events.

Low serum adiponectin is independently associated with both the metabolic syndrome and angiographically determined coronary atherosclerosis.

BACKGROUND: We aimed at investigating serum adiponectin in patients with the metabolic syndrome (MetS), in patients with angiographically diagnosed coronary artery disease (CAD), and in patients who had both, the MetS and CAD. METHODS: We enrolled 687 consecutive patients undergoing coronary angiography for the evaluation of CAD. RESULTS: From our patients, 178 had neither the MetS (Adult Treatment Panel III definition) nor significant CAD (MetS-/CAD-), 91 had the MetS, but not significant CAD (MetS+/CAD-), 251 did not have the MetS but had significant CAD (MetS-/CAD+), and 167 had both, the MetS and significant CAD (MetS+/CAD+). Serum adiponectin was highest (12.1+/-8.3 microg/ml) in MetS-/CAD- subjects. It was significantly lower in MetS+/CAD- (9.5+/-7.3 microg/ml; p=0.001) and in MetS-/CAD+ patients (9.2+/-5.3 microg/ml; p<0.001) and lowest in MetS+/CAD+ patients (6.7+/-3.8 microg/ml) in whom it was significantly lower than in MetS-/CAD-, MetS+/CAD-, and MetS-/CAD+ patients (p<0.001 for all comparisons). In analysis of covariance the MetS and significant CAD proved associated with serum adiponectin in a mutually independent manner. CONCLUSIONS: Low serum adiponectin is independently associated with both the MetS and coronary atherosclerosis.

The -11377 C>G promoter variant of the adiponectin gene, prevalence of coronary atherosclerosis, and incidence of vascular events in men.

No prospective data demonstrating an association between the -11377 C > G adiponectin gene promoter variant and cardiovascular risk are available. We therefore prospectively evaluated the cardiovascular risk associated with adiponectin gene single nucleotide polymorphisms (SNPs) including SNP -11377 in a consecutive series of men undergoing coronary angiography. We recorded vascular events over four years in 402 men undergoing coronary angiography for the evaluation of coronary artery disease. No significant associations of SNPs +276 G > T and +45 T > G with serum adiponectin, with significant coronary stenoses >50%, or with vascular events were observed. However, for SNP -11377 C > G, serum adiponectin levels significantly decreased (p(trend) = 0.003), and the prevalence of significant coronary stenoses significantly increased from the CC over the GC to the GG genotype (p(trend) = 0.004). Prospectively, the risk of vascular events significantly increased from the CC over the CG to the GG genotype of this SNP (adjusted hazard ratios 1.555 [0.957 - 2.525] and 2.309 [1.067 - 4.998], respectively; p(trend) = 0.014). The -11377 C > G adiponectin gene promoter variant is i) associated with decreased serum adiponectin levels, ii) correlated with the presence of coronary atherosclerosis and iii) significantly predictive of vascular events among men undergoing coronary angiography.

Relationship between glomerular filtration rate and the adipokines adiponectin, resistin and leptin in coronary patients with predominantly normal or mildly impaired renal function.

BACKGROUND: Due to their molecular weight, it is possible that the adipokines adiponectin, resistin and leptin accumulate when glomerular filtration rate (GFR) is decreased. In reduced renal clearance, altered serum concentrations of these proteins might affect cardiovascular risk. The objective of the study was to investigate the relationship between adipokine concentrations and GFR. METHODS: The association between GFR, as determined by the abbreviated MDRD equation, and the concentrations of the adipokines adiponectin, resistin and leptin was assessed in a cohort of coronary patients (n=538; 363 male, 165 female). After calculation of correlations between GFR and adipokine concentrations, the association was further assessed by analysis of covariance following adjustment for age, gender, BMI, presence of type 2 diabetes, presence of hypertension, history of smoking as well as for serum lipid concentrations. RESULTS: Mean GFR in our study population was 68.74+/-15.27 ml/min/1.73 m(2). 74.3% of the patients had a GFR >60 ml/min/1.73 m(2), 24% of the patients had a GFR between 30 and 60 ml/min/1.73 m(2), and 1.7% of the patients had a GFR <30 ml/min/1.73 m(2). There were significant inverse correlations between adiponectin (r=-0.372; p<0.001), resistin (r=-0.227; p<0.001) and leptin (r=-0.151; p=0.009) concentrations and GFR. After multivariate adjustment, the associations remained significant for adiponectin and resistin. Subgroup analysis in patients with GFR >60 ml/min/1.73 m(2) showed a significant correlation between GFR and adiponectin as well as leptin concentrations. However, after adjustment, these associations no longer were significant. CONCLUSIONS: There is an independent association between GFR and the serum concentrations of adiponectin and resistin. However, this association is not present at GFR >60 ml/min/1.73 m(2). This finding suggests that adipokine concentrations in mildly impaired and normal renal function are influenced by factors other than GFR.

Evaluation of two fully automated novel enzyme-linked immunosorbent assays for the determination of human adiponectin in serum.

BACKGROUND: In contrast to RIA, recently available ELISAs provide the potential for fully automated analysis of adiponectin. To date, studies reporting on the diagnostic characteristics of ELISAs and investigating on the relationship between ELISA- and RIA-based methods are rare. METHODS: Thus, we established and evaluated a fully automated platform (BEP 2000; Dade-Behring, Switzerland) for determination of adiponectin levels in serum by two different ELISA methods (competitive human adiponectin ELISA; high sensitivity human adiponectin sandwich ELISA; both Biovendor, Czech Republic). Further, as a reference method, we also employed a human adiponectin RIA (Linco Research, USA). Samples from 150 patients routinely presenting to our cardiology unit were tested. RESULTS: ELISA measurements could be accomplished in less than 3 h, measurement of RIA had a duration of 24 h. The ELISAs were evaluated for precision, analytical sensitivity and specificity, linearity on dilution and spiking recovery. In the investigated patients, type 2 diabetes, higher age and male gender were significantly associated with lower serum adiponectin concentrations. Correlations between the ELISA methods and the RIA were strong (competitive ELISA, r=0.82; sandwich ELISA, r=0.92; both p<0.001). However, Deming regression and Bland-Altman analysis indicated lack of agreement of the 3 methods preventing direct comparison of results. The equations of the regression lines are: Competitive ELISA=1.48 x RIA-0.88; High sensitivity sandwich ELISA=0.77 x RIA+1.01. CONCLUSIONS: Fully automated measurement of adiponectin by ELISA is feasible and substantially more rapid than RIA. The investigated ELISA test systems seem to exhibit analytical characteristics allowing for clinical application. In addition, there is a strong correlation between the ELISA methods and RIA. These findings might promote a more widespread use of adiponectin measurements in clinical research.

Adult Treatment Panel III 2001 but not International Diabetes Federation 2005 criteria of the metabolic syndrome predict clinical cardiovascular events in subjects who underwent coronary angiography.

OBJECTIVE: The International Diabetes Federation (IDF) has recently established a worldwide consensus definition of the metabolic syndrome. No prospective data are available on the cardiovascular risk associated with this new metabolic syndrome definition. RESEARCH DESIGN AND METHODS: In a prospective study of 750 coronary patients, we recorded vascular events over 4 years. RESULTS: From our patients, 37.3% (n = 280) had the metabolic syndrome according to the Adult Treatment Panel III (ATPIII) definition and 45.5% (n = 341) according to the IDF definition. The metabolic syndrome as defined by the ATPIII criteria significantly predicted vascular events (adjusted hazard ratio 1.745 [95% CI 1.255-2.427]; P = 0.001), but the metabolic syndrome as defined by IDF criteria did not (1.189 [0.859-1.646]; P = 0.297). Accordingly, event-free survival was significantly lower among patients who fulfilled the ATPIII but not the IDF criteria than among those who met the IDF but not the ATPIII criteria (P = 0.012). The metabolic syndrome as defined by ATPIII criteria remained significantly predictive of vascular events after adjustment for type 2 diabetes but not after additional adjustment for the metabolic syndrome components high triglycerides and low HDL cholesterol. These lipid traits in turn proved significantly predictive of vascular events even after adjustment for the metabolic syndrome. CONCLUSIONS: The ATPIII definition of the metabolic syndrome confers a significantly higher risk of vascular events than the IDF definition. However, among angiographied coronary patients, even the ATPIII definition of the metabolic syndrome does not provide prognostic information beyond its dyslipidemic features.

The metabolic syndrome, insulin resistance, and cardiovascular risk in diabetic and nondiabetic patients.

CONTEXT: The contribution of insulin resistance per se to the vascular risk conferred by the metabolic syndrome (MetS) is not known; conversely, it is uncertain whether insulin resistance confers vascular risk beyond the entity of the MetS. OBJECTIVE: The objective of this study was to investigate the impact of the MetS (Adult Treatment Panel III criteria) and insulin resistance (as estimated by the homeostasis model assessment index) on the incidence of vascular events. DESIGN AND PATIENTS: This was a prospective cohort study enrolling 750 consecutive patients undergoing coronary angiography for the evaluation of coronary artery disease. SETTING: The study was performed at a tertiary care clinical research center. MAIN OUTCOME MEASURE: The main outcome measure was the incidence of vascular events over 2.3 yr. RESULTS: Both the MetS and insulin resistance predicted vascular events after controlling for non-MetS risk factors [hazard ratio (HR), 2.74 (95% confidence interval, 1.71-4.39; P < 0.001) and 1.51 (1.24-1.84; P < 0.001), respectively]. After additional adjustment for insulin resistance, the MetS remained significantly predictive of vascular events [HR, 2.69 (1.57-4.64); P < 0.001], and conversely, insulin resistance remained significantly predictive of vascular events despite adjustment for the MetS [standardized HR, 1.41 (1.14-1.75); P = 0.002]. Additional adjustment for the presence of type 2 diabetes revealed that both the MetS [adjusted HR, 2.57 (1.47-4.51); P = 0.001] and homeostasis model assessment of insulin resistance [standardized adjusted HR, 1.37 (1.09-1.73); P = 0.007] significantly predicted vascular events independent from diabetes status. CONCLUSIONS: Both the MetS and insulin resistance are strong and mutually independent predictors of vascular risk among angiographed coronary patients.

Is atherosclerosis in diabetes and impaired fasting glucose driven by elevated LDL cholesterol or by decreased HDL cholesterol?

OBJECTIVE: To evaluate the atherogenicity of lipids in coronary patients with normal fasting glucose (NFG), impaired fasting glucose (IFG), and type 2 diabetes. RESEARCH DESIGN AND METHODS: Serum lipid values, the presence of angiographic coronary artery disease (CAD) at baseline, and the incidence of vascular events over 2.3 years were recorded in 750 consecutive patients undergoing coronary angiography. RESULTS: Triglycerides significantly (P < 0.001) increased and HDL cholesterol (P < 0.001) as well as LDL particle diameter (P < 0.001) significantly decreased from subjects with NFG <5.6 mmol/l (n = 272) over patients with IFG > or =5.6 mmol/l (n = 314) to patients with type 2 diabetes (n = 164). Factor analysis revealed two factors in the lipid profiles of our patients: triglycerides, HDL cholesterol, apolipoprotein A1, and LDL particle diameter loaded high on an HDL-related factor, and total cholesterol, LDL cholesterol, and apolipoprotein B loaded high on an LDL-related factor. In patients with type 2 diabetes, the HDL-related factor (odds ratio 0.648 [95% CI 0.464-0.904]; P = 0.011), but not the LDL-related factor (0.921 [0.677-1.251]; P = 0.597), was associated with significant coronary stenoses > or =50%. Consistently, in the prospective study, the HDL-related factor (0.708 [0.506-0.990]; P = 0.044), but not the LDL-related factor (1.362 [0.985-1.883]; P = 0.061), proved significantly predictive for vascular events in patients with type 2 diabetes. CONCLUSIONS: The low HDL cholesterol/high triglyceride pattern is associated with the degree of hyperglycemia. In coronary patients with type 2 diabetes, this pattern correlates with the prevalence of CAD and significantly predicts the incidence of vascular events.