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Copyright of Diabetes & Metabolism is the property of Masson Editeur and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Background: Obstructive sleep apnoea syndrome (OSAS), an obesity comorbidity, is an independent risk factor for diabetes (T2DM) and major adverse cardiovascular events (MACE). While OSAS prevalence and association with MACE are well documented in the general population, such information is not available in T2DM. Methods: We analyzed 467 consecutive male T2DM outpatients in whom OSAS was diagnosed through Epworth''s Sleepiness Scale (ESS), overnight oximetry and polysomnography. OSAS (+) (n =43) were compared to OSAS (−) (n =424) regarding cardiovascular (CV) risk factors and/or MACE. Results: Mean (1 SD) age was 64 (12) years, diabetes duration 13 (9) years. Metabolic syndrome prevalence was 77%, HbA1c 7.6 (1.6) %. OSAS prevalence was 9%. There were no differences in age, diabetes duration, smoking, blood pressure and lipids between OSAS (+) and (−). There were significant differences in ESS score, ethanol intake, hypertension, BMI, waist, relative/absolute fat, conicity index, and visceral fat, all significantly higher in OSAS (+). Nasal continuous positive airway pressure was used by 37% of OSAS (+). HOMA hyperbolic product was significantly lower in OSAS (+), as a result of more severe insulin resistance. OSAS (+) were less often in primary prevention (PP) for CV disease than OSAS (−) (43% vs. 66%; p <0.003). MACE and coronary artery disease (CAD) prevalence were 61 and 63% higher in OSAS (+) (61% vs. 38%; p <0.01 and 44% vs. 27%; p <0.03), who showed a higher stroke prevalence (15% vs. 8%; NS). Conclusions: OSAS is frequent in male T2DM patients. With gender and diabetes ruled out as confounders, our results indicate a strong association between OSAS and CV risk factors, such as hypertension, BMI, waist, relative/absolute/visceral fat, conicity, liver steatosis and hypoandrogenicity. Using the T2DM-specific UKPDS calculator, CVD risk estimates were high though not different between OSAS subgroups in primary CV prevention. OSAS patients with T2DM showed a marked increase in MACE/CAD, making a case for aggressive tertiary prevention. [Copyright &y& Elsevier]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background: Ethnicity is a modifying factor affecting the natural history and presentation of T2DM through genetic predisposition and socio-cultural determinants. Among ethnically at-risk subjects are economic migrants from Southern latitudes. In this cross-sectional evaluation, we report the phenotypic characterization of first generation Maghrebian migrants with T2DM, mostly from Morocco, and living in Belgium, with reference to gender-based North-Caucasian Belgian T2DM cohorts. We focused on both the prevalence and determinants of metabolic syndrome (MetS) and its related anthropometry, as well as on the hyperbolic product determinants of glucose homeostasis. Method: Fifty-three Maghrebian patients were compared with 558 North-Caucasian Belgian patients, all suffering from T2DM and consecutively followed at the outpatient clinic of St-Luc Academic Hospital in Brussels. In these two groups, we performed HOMA-modeling of insulin sensitivity (S), β-cell function (β), hyperbolic product (β×S) and (β×S) deficit standardized to lifetime. We also collected anthropometric and biochemical characteristics alongside the prevalence of MetS (AHA/NHLBI criteria), its components, and that of micro- and macrovascular complications. Results: Maghrebians were younger than North-Caucasians, and diagnosed with diabetes a mean 6 years earlier. There were, however, marked gender differences in anthropometry and glucose homeostasis determinants, with significant differences in Maghrebians males with respect to BMI, waist circumference, fat mass, conicity index, fat-free mass or fat-free mass index. The prevalence of hypertension was lower in Maghrebians, and that of AHA/NHLBI-defined metabolic syndrome was not different between cohorts, nor were HOMA-modeled insulin sensitivity (HOMA S). The hyperbolic product (β×S) was significantly lower in Maghrebians males, who had a more severe insulin secretory defect compared with North-Caucasians. Such β×S defect was especially pronounced in males once standardized to lifetime, in keeping with the pharmaco-therapeutic profile, glucose-lowering therapies and poorer metabolic control. Retinopathy was more frequent and severe in Maghrebians. Conclusion: Maghrebians’ true residual β-cell function (β×S) showed accelerated deterioration in T2DM males compared with age-comparable North-Caucasians. Such a faster deterioration hypothesis may easily account for the observed differences in HbA1c and in requirements for glucose-lowering therapies, including insulin monotherapy. [Copyright &y& Elsevier]

Summary: Aims: An unfavourable upregulation of neurohormonal profile is present in type 2 diabetes (T2DM). Little is known regarding neurohormonal profile and cardiovascular (CV) risk in diabetic women in primary prevention. Methods: We therefore explored gender-associated disparities in neurohormonal profile and modeled cardiovascular risk in this population (n =231) and modeled its 10-year risk of lethal and non-lethal coronary heart disease (CHD) and stroke using the UKPDS Risk Engine, a diabetes-specific risk calculator. Results: There were significant differences between female and male patients (n =311) with respect to all measured neurohormones, which were higher in women by a mean 27% for N-terminal pro-atrial natriuretic peptide, 8% for Big endothelin-1 (Big ET-1), 25% for brain natriuretic peptide and 24% for urotensin II. While risk estimates for women were significantly lower than those in males with respect to non-fatal and fatal CHD, fatal CHD, non-fatal and fatal stroke, they were nevertheless worryingly high for females, reaching 68%, 72%, and 76% of the corresponding risks in males. Female patients with T2DM in primary prevention with a high prevalence of hypertension and metabolic syndrome (MetS) exhibit a significant sexual dimorphism in circulating neurohormones. Conclusions: We conclude that these incremental differences may intervene in raising the true CV risk observed in female subjects with diabetes or insulin resistance, or in accruing the predicted risk computed by models such as the UKPDS Risk Engine. [Copyright &y& Elsevier]

Summary: Cystic fibrosis (CF), a common autosomal recessive condition, often involves the CFTR ΔF508 mutation in the homo- or heterozygous state. Due to continuously improving survival rates, a secondary form of diabetes mellitus (cystic fibrosis-related diabetes or CFRD) is now becoming a major comorbidity associated with CF. The etiopathogeny of CFRD is usually ascribed to pancreatic exocrine/endocrine insufficiency which itself correlates with CFTR mutation. While insulin deficiency seems to play the major role in CFRD, a relative insulin resistance component was also proposed. In a local cohort of seventy-six patients with the ΔF508 mutation, we demonstrate using HOMA (Homeostasis Model Assessment) that impairment of the true underlying insulin secretion, as reflected by (B×S), is the hallmark of (pre)diabetes in CF. The initiation of insulin therapy is associated with a significant increase in body mass index as well as a trend towards improvement in lung function. Regular screening for (pre)diabetes in CF should on that ground be performed on a regular basis. [Copyright &y& Elsevier]

Summary: Background: Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) prevalence is increasing in developing countries as a result of urbanization, with widespread access to calorically richer foods. This cross-sectional study aimed at documenting MetS prevalence, the presence of its discrete components and the phenotypic characteristics including HOMA hyperbolic product of 1st generation sub-Saharan African migrants living in Belgium, and at comparing them to those of a reference white Caucasian autochthonous Belgian population with T2DM. Method: 337 Belgian patients were compared with 117 sub-Saharan African patients, all suffering from T2DM. In these two groups, we performed HOMA-modeling of insulin sensitivity (S) and β-cell function (β), as well the hyperbolic product (β × S), and we collected anthropometric and biochemical characteristics alongside the prevalence of MetS (NCEP ATP III), its components, and that of micro- and macro-vascular complications. Results: In the sub-Saharan group, waist circumference was lower, and the lipid profile showed higher HDL and lower triglycerides levels. This ensued a lower prevalence of categorical MetS in this population in male subjects. Diagnosis of T2DM occurred earlier in this sub-Saharan population, and while β × S was higher in those subjects compared with Caucasians, the demographics suggest that lifetime insulin secretion decreases faster in these otherwise less insulin-resistant subjects. Conclusion: In male sub-Saharan African subjects with T2DM, the MetS prevalence is lower than in sub-Saharan females, and lower than that recorded in Belgian diabetic subjects. This difference resulted from lower girth circumference and less atherogenic lipid profile. However, this sub-Saharan population had earlier onset diabetes with concurrent insulin resistance and earlier loss of insulin secretion. [Copyright &y& Elsevier]

Summary: Background and objectives: Insulin modulates key regulators of vascular tone, including endothelin-1 (ET-1), hence insulin resistance (IR) and/or hyperinsulinemia may contribute to the pathogenesis of hypertension and cardiovascular disease (CVD). Imbalance in ET-1/nitric oxide may link IR to CVD. Little is known on the relation between neurohormones, metabolic syndrome (MetS) categories (1–5/5) in type 2 diabetes (T2DM). We therefore sought to assess the relationship between neurohormonal profile, CVD and MetS in a large T2DM cohort, as well as the associations between neurohormones, insulinaemia, insulin sensitivity, CVD markers and events within MetS categories. Methods: In 455 consecutive T2DM patients with or without MetS [MetS (+)/(−)] defined according to AHA/NHLBI, we assessed the following: MetS categories, HOMA-S, circulating Big-endothelin-1 (Big ET-1), natriuretic peptides and macroangiopathy [Macro (+)/(−)]. Results: Big ET-1 was higher by 30%, in MetS (+) (median [IQ range]): 5.2 [4.3–6.0]pgml−1 in MetS (−) (n =75) versus 6.7 [5.2–9.1]pgml−1 in MetS (+) (n =380; P <0.0001). There was a progression in Big ET-1 across MetS scores: 6.3 [5.2–8.5]pgml−1 in MetS (+) 3/5; 6.9 [5.1–9.4]pgml−1 in MetS (+) 4/5 and 7.3 [5.6–9.5]pgml−1 in MetS (+) 5/5 (NS). The incremental difference in Big ET-1 between MetS (+) and MetS (−) was found out both in the absence or presence of macroangiopathy: 4.55 [4.03–5.25]pgml−1 in MetS (−) Macro (−) versus 5.70 [4.60–7.50]pgml−1 in MetS (+) Macro (−) (P <0.0001), and 5.70 [5.20–7.60]pgml−1 in MetS (−) Macro (+) versus 7.60 [5.80–10.13]pgml−1 in MetS (+) Macro (+) (P <0.0001), respectively. Such patterns were not observed with natriuretic peptides. Comparison between MetS (+) Macro (−) versus MetS (−) Macro (+) confirms that such incremental differences should not be solely ascribed to parallel shifts in IR and/or compensatory hyperinsulinaemia. Conclusions: Big ET-1 is raised in T2DM patients with MetS, and its level proceeds stepwise to MetS categories. Elevated Big ET-1 is present in all categories of MetS patients, with or without macroangiopathy. The ascent in Big ET-1 found in MetS (+) without macrovascular disease is of the same magnitude as that conferred by the presence of macroangiopathy. [Copyright &y& Elsevier]

OBJECTIVE -- We sought to determine the clinical phenotype of adolescent/adult patients with cystic fibrosis, according to heterozygosity or homozygosity for cystic fibrosis transmembrane regulator (CFTR) ΔF508 mutation, and to analyze their characteristics according to glucose tolerance status. RESEARCH DESIGN AND METHODS -- A total of 76 cystic fibrosis patients with CFTR ΔF508 mutation (33 heterozygous and 43 homozygous) stratified according to normal glucose tolerance (NGT) (n = 51) or abnormal glucose homeostasis (AGH) (impaired fasting glucose, impaired glucose tolerance, or diabetes; n = 25) had their homeostasis model assessment (HOMA) of β-cell function and of insulin sensitivity and hyperbolic product (β-cell function X insulin sensitivity [B X S]) measured. Pancreatic exocrine insufficiency was inferred from pancreatine requirements. Clinical effects of insulin therapy on weight and lung function were recorded. RESULTS -- AGH was observed in 24 and 40% of heterozygous and homozygous subjects, respectively. AGH patients were older than NGT patients (mean ± SD age 29 ± 10 vs. 23 ± 8 years, P = 0.006), and their β-cell function was lower (93 ± 49 vs. 125 ± 51%, P = 0.011). Insulin sensitivity values were comparable in NGT and AGH patients. A lower B X S product was observed in AGH, although it was nonsignificant when adjusted for error propagation. Pancreatic insufficiency was observed in 52 and 100% of heterozygous and homozygous patients (P = 0.001). CONCLUSIONS -- Pre-diabetes and diabetes represent frequent comorbidities in CFTR ΔF508 mutation in the homozygous or heterozygous states. Impairment of insulin secretion, as shown by HOMA, is an important determinant when compared with the magnitude of compensation from insulin sensitivity. Given the high prevalence of abnormal glucose tolerance, screening for (pre-)diabetes is mandatory. Insulin supplementation in diabetic subjects with CFTR ΔF508 mutation seems a rational therapy for consideration, although this does not preclude that therapy directed toward insulin resistance could also interact. [ABSTRACT FROM AUTHOR]

Summary: Objectives: We sought to use the Discriminant Ratio (DR) method to compare the respective performance of low-density lipoprotein-cholesterol (LDL-C)/high-density lipoprotein (HDL)-C and apolipoprotein B (ApoB)/ApoA1 ratios to rank diabetics according to dyslipidemia severity. Background: ApoB/ApoA1 was proposed as robust alternative to well-established LDL-C/HDL-C in ranking subjects according to their cardiovascular risk, while non-HDL-C was advocated as secondary target in metabolic syndrome. Nevertheless, the discriminatory superiority of these new markers remains unknown in diabetes. Methods: Forty-five subjects with types 1 (n =23) and 2 diabetes (n =22) were studied. Total-, HDL-C and triglycerides were measured by enzymatic assays and ApoB and ApoA1 by immunonephelometry. DR is the ratio of the underlying between-subject standard deviation (S.D.) to the within-subject S.D., calculated from log duplicates sampled on different days. Correlation coefficients between pairs of measurements were adjusted to include an estimate of the underlying correlation, since standard coefficients tend to underestimate the true correlation between tests due to the presence of within-subject variation. Results: Mean values (day 1 (±1S.D.)) were 2.25 (0.87) for LDL-C/HDL-C, and 0.63 (0.20) for ApoB/ApoA1, respectively. The highest DRs were those of total C/HDL-C and non-HDL-C/HDL-C (2.33 and 2.38; p <0.05 and <0.02 versus the DR of LDL-C/HDL-C). The DR of ApoB/ApoA1 (2.12) was non-significantly higher than that of LDL-C/HDL-C (1.45). Conclusions: ApoB/ApoA1 does not provide greater discrimination than LDL-C/HDL-C to rank a diabetic population. The best approach is obtained with total C/HDL-C and new candidate marker non-HDL-C/HDL-C, both easy and cost-effective means to stratify diabetics according to their lipid profile. [Copyright &y& Elsevier]

Summary: Background: It is established from a large corpus of clinical studies that even moderately elevated plasma total homocysteine levels are associated with an increased risk for cardiovascular disease, in non-diabetic and in type 2 diabetic individuals. However, recent prospective interventions trials aimed at decreasing plasma homocysteine concentrations using vitamin supplementation (folic acid, Vitamin B-12, Vitamin B-6) were unable to demonstrate a clear preventive benefit on cardiovascular events. In this view, hyperhomocysteinemia could rather represent a marker of vascular risk than a true risk factor per se, as previously strongly hinted at. Objectives: The aim of this review is to analyse the pro- and contradictory data concerning a potential pathogenic role of hyperhomocysteinemia in the development of atherosclerosis, in particular in patients with type 2 diabetes, who are at high risk of developing macroangiopathy. Conclusions: Hyperhomocysteinemia could be a marker of atherosclerosis rather than a causal factor. [Copyright &y& Elsevier]

Background. Although diabetes in elderly persons is generally type 2, the metabolic abnormalities associated with aging suggest that elderly persons may differ from younger persons with type 2 diabetes. In addition, nonobese elderly persons with type 2 diabetes show a marked impairment in insulin release accompanied by mild insulin resistance, whereas obese elderly persons have marked insulin resistance in the presence of "adequate" levels of insulin. Other factors that could adversely affect glucose tolerance in aging include drug use, associated disease, and other stressful conditions commonly encountered in geriatric inpatients units. The authors' objectives in this study were 1) to prospectively assess the prevalence of glucose homeostasis abnormalities among elderly hospitalized patients and the degree to which it reflects abnormalities in insulin secretion or insulin sensitivity using homeostasis model assessment of fasting glucose, insulin, and C- peptide; and 2) to define the social, functional, pathologic, and nutritional characteristics of persons with impaired glucose tolerance or diabetes. Methods. Ninety-eight patients underwent a comprehensive geriatric assessment. Determinants of glucose homeostasis were assessed using the homeostasis model assessment, which provides estimates of β-cell function (%B) and insulin sensitivity (%S). Results. Twelve patients (12%) had fasting glucose concentrations greater than 110 mg/dl. Four patients had impaired fasting glucose levels greater than 110 mg/dl but less than 126 mg/dl (IFG group), and 8 patients had levels greater than 126 mg/dl (type 2 diabetes group). Except for a higher proportion of women in the IFG-diabetes group, the latter did not exhibit significant differences in functional, morbidity, or nutritional characteristics compared with the normal glucose tolerance group. The entire cohort (n = 98) presented with a mean (±SD) %B of 71% ± 47% and a mean %S of 208% ± 198%.... [ABSTRACT FROM AUTHOR]

In order to assess insulin sensitivity (IS) and β-cell function (B) in anorexia nervosa (AN) we measured fasting plasma glucose (FPG), immunoreactive insulin and C-peptide levels in 33 consecutive subjects with AN for modelling with Homeostasis Model Assessment (HOMA). Mean (± 1 SD) fasting glucose and insulin levels were 71 ± 10 mg dl[sup -1] and 7.3 ± 2.8 μU ml[sup -1] respectively. Median IS and B (% normal) were 143 (percentile 25–75: 95–194) and 127 (102–157). When subjects were stratified according to median IS, those with high insulin sensitivity were of similar age, AN duration, weight, BMI, and body composition to those with normal IS. However, FPG was significantly lower in the higher insulin sensitivity subgroup (67 ± 11 versus 75 ± 7 mg dl[sup -1] ; p < 0.03), and two patients presented with symptomatic hypoglycaemia. We conclude that patients with AN exhibit a trend toward increased IS, which is not associated with any specific clinical characteristic. In the whole cohort, B was either normal or moderately increased. Copyright © 2002 John Wiley & Sons, Ltd and Eating Disorders Association. [ABSTRACT FROM AUTHOR]

Presents information on a study which determined the distribution of plasma total homocysteine concentration in type 2 diabetes and its relationship to chronic complications and insulin resistance. Methodology; Results of the study; Conclusions.

Adequate comparisons of the relative performance of different tests of beta-cell function are not available. We compared discrimination of commonly used in vivo tests of beta-cell function across a range of glucose tolerance in seven subjects with normal glucose tolerance (NGT), eight subjects with impaired glucose tolerance (IGT), and nine subjects with type 2 diabetes. In random order, each subject underwent two of each of the following tests: 1) frequently sampled 0.3-g/kg intravenous glucose tolerance test (FSIVGTT) with MinMod analysis; 2) homeostasis model assessment (HOMA) from three samples at 5-min intervals with a model incorporating immunoreactive or specific insulin measurements; and 3) continuous infusion of 180 mg x min(-1) x m(-2) glucose with model assessment (CIGMA) of three samples at 50, 55, and 60 min (1-h CIGMA) and at 110, 115, and 120 min (2-h CIGMA). The discrimination of each test was assessed by the ratio of the within-subject SD to the underlying between-subject SD, the discriminant ratio (DR). The degree to which tests measured the same physiological variable was assessed using Pearson's correlation coefficient adjusted for attenuation due to test imprecision. An unbiased line of equivalence, taking into account the imprecision of both tests, was used to compare results. Beta-cell function assessed from HOMA and beta-cell function assessed from CIGMA (CIGMA%beta) (using immunoreactive insulin) had higher DRs than first-phase intravenous glucose tolerance test-derived incremental insulin peak, area, insulin-to-glucose index, and acute insulin response to glucose from FSIVGTT-MinMod. CIGMA%beta (immunoreactive insulin) had the highest DR. FSIVGTT-derived first-phase insulin response tests correlated only moderately with HOMA and CIGMA. Using specific rather than immunoreactive insulin for HOMA and CIGMA did not improve discriminatory power. Simple tests such as HOMA and CIGMA, using immunoreactive insulin, offer better beta-cell function discrimination across subjects with NGT, IGT, and type 2 diabetes than measurements derived from FSIVGTT first-phase insulin response. [ABSTRACT FROM AUTHOR]

Background: Raised levels of lipoprotein(a) [Lp(a)] are causally associated with incident macroangiopathy and aortic valvular calcification in (non)diabetic subjects. Objective: In type 2 diabetes (T2DM), there is an inverse, J-shaped relationship between elevated Lp(a) and prevalent microangiopathies. This work assessed whether this inverse association also exists in type 1 diabetes (T1DM). Methods: The cardiometabolic phenotype of 357 patients with T1DM was determined, alongside routine lipids, Lp(a), non-Lp(a)-LDL-C, apolipoprotein B100, apolipoprotein A-I, and atherogenic dyslipidemia. Patients in the 1st tertile of Lp(a) ([TI]; n=119; median Lp(a) 6 nmol/L) were compared to those in the 3rd tertile of Lp(a) ([TIII]; n=119; median Lp(a) 100 nmol/L). Results: There were no significant differences between [TI] and [TIII] patients regarding gender, diabetes duration, HbA1c, smoking, BMI, hypertension, GFR, (micro)albuminuria, cerebrovascular disease, routine lipids (total C; LDL-C; HDL-C; TG), apolipoprotein B100, apolipoprotein A-I, non-Lp(a)-LDL-C, and frequency/intensity of statin use. Compared to [TIII], [TI] patients were younger (48 vs. 53 years), had lower body fat (24 vs. 27%), and higher muscle mass (36 vs. 34%; all p<0.05). After adjusting for age, [TIII] had more overall microangiopathy (+37%; 57 vs. 45%) and diabetic retinopathy (+34%; 51 vs. 38%; 0.0441). They also had an increased prevalence of overall macroangiopathy (+211%; 19 vs. 9%; p 0.0265) and coronary artery disease (+250%; 15 vs. 6%; p 0.0238). Among [TIII] patients, 35% were in the highest CV risk category, vs. 16% of [TI] (p 0.0008). Conclusion: In addition to the risk of macrovascular complications, a high level of Lp(a) is associated with an increased frequency of retinal microangiopathy in T1DM patients, contrary to what was observed in T2DM. On the other hand, the frequency of macroangiopathy was increased in T1DM just like in T2DM and nondiabetic patients. Disclosure: S. Van haare heijmeijer: None. M. P. Hermans: None. [ABSTRACT FROM AUTHOR]

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome. [ABSTRACT FROM AUTHOR]

The global obesity epidemic continues to rise worldwide. In this context, unraveling new interconnections between biological systems involved in obesity etiology is highly relevant. Dysregulation of the endocannabinoidome (eCBome) is associated with metabolic complications in obesity. This study aims at deciphering new associations between circulating endogenous bioactive lipids belonging to the eCBome and metabolic parameters in a population of overweight or obese individuals with metabolic syndrome. To this aim, we combined different multivariate exploratory analysis methods: canonical correlation analysis and principal component analysis, revealed associations between eCBome subsets, and metabolic parameters such as leptin, lipopolysaccharide-binding protein, and non-esterified fatty acids (NEFA). Subsequent construction of predictive regression models according to the linear combination of selected endocannabinoids demonstrates good prediction performance for NEFA. Descriptive approaches reveal the importance of specific circulating endocannabinoids and key related congeners to explain variance in the metabolic parameters in our cohort. Analysis of quartiles confirmed that these bioactive lipids were significantly higher in individuals characterized by important levels for aforementioned metabolic variables. In conclusion, by proposing a methodology for the exploration of large-scale data, our study offers additional evidence of the existence of an interplay between eCBome related-entities and metabolic parameters known to be altered in obesity. [ABSTRACT FROM AUTHOR]

Background: The role of herbal products in the prevention of cardiovascular disease requires supporting evidence. This open pilot study assessed the effect of 2-month supplementation of a combination of olive leaf and fruit extracts (Tensiofytol®, Tilman SA, Baillonville, Belgium) in the clinical management of hypertension and metabolic syndrome (MetS). Methods: A total of 663 (pre)-hypertensive patients were enrolled by general practitioners and supplemented for two months with Tensiofytol®, two capsules per day (100 mg/d of oleuropein and 20 mg/d of hydroxytyrosol). Systolic and diastolic blood pressures (SBP/DBP) were measured before and after treatment. Markers of MetS, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose (FG) and waist circumference (WC), were also examined. Results: Significant reductions (p < 0.0001) in SBP/DBP (13 ± 10/7.1 ± 6.6 mmHg) were observed and similarly in pre-diabetic and diabetic patients. Improvements in SBP/DPB were independent of age and gender but greater for elevated baseline SBP/DBP. Tensiofytol® supplementation also significantly improved markers of MetS, with a decrease of TG (11%), WC (1.4%) and FG (4.8%) and an increase of HDL-C (5.3%). Minor side effects were reported in 3.2% patients. Conclusions: This real-life, observational, non-controlled, non-randomized pilot study shows that supplementation of a combination of olive leaf and fruit extracts may be used efficiently and safely in reducing hypertension and MetS markers. [ABSTRACT FROM AUTHOR]

Background: Maternal mortality (MM) remains a real scourge that hits hardest in the poorest regions of the world, particularly those affected by conflict. However, despite this worrying reality, few studies have been conducted about MM ratio in the Democratic Republic of Congo (DRC). The study aimed to describe the trends as well as the epidemiological profile and causes of reported institutional maternal deaths between 2013 and 2022 in Eastern DRC. Methods: A retrospective descriptive study was conducted between March 2023 and August 2023 in eight Health Zones (HZ), five in South Kivu Province (Mwana, Minova, Miti-Murhesa, Kamituga and Idjwi) and three in North Kivu Province (Kirotshe, Karisimbi and Kayna) in the eastern region of the DRC. Our study covers 242 health facilities: 168 health centers (HC), 16 referral health centers (RHCs),50 referral hospitals (RH) and 8 general referral hospitals (GRHs). Data from registers and medical records of maternal deaths recorded in these zones from 2013–2022 were extracted along with information on the number of deliveries and live births. Sociodemographic, clinical parameters, blood and ultrasound tests and suspected causes of death between provinces were assessed. Results: In total, we obtained 177 files on deceased women. Of these, 143 (80.8%) were retained for the present study, including 75 in the 3 HZs of North Kivu and 68 in the 5 HZs of South Kivu. From 2013 to 2022, study sites experienced two significant drops in maternal mortality ratio (MMR) (in 2015 and 2018), and a spike in 2016–2017. Nonetheless, the combined MMR (across study sites) started and ended the 10-year study period at approximately the same level (53 and 57 deaths per 100,000 live births in 2013 and 2022 respectively). Overall, 62,6% of the deaths were reported from secondary hospital. Most deaths were of married women in their thirties (93.5%). Almost half (47.8%) had not completed four antenatal consultations. The main direct causes of death were, in decreasing order of frequency: post-partum haemorrhage (55.2%), uterine rupture (14.0), hypertensive disorders (8.4%), abortion (7.7%) puerperal infections (2.8%) and placental abruption (0.7%). When comparing among provinces, reported abortion-related maternal mortality (14.1% vs 0%) was more frequent in North Kivu than in South Kivu. Conclusion: This study imperatively highlights the need for targeted interventions to reduce maternal mortality. By emphasizing the crucial importance of antenatal consultations, intrapartum/immediate post-partum care and quality of care, significant progress can be made in guaranteeing maternal health and reducing many avoidable deaths. [ABSTRACT FROM AUTHOR]

The neutral result of the PROMINENT trial has led to questions about the future for pemafibrate. This commentary discusses possible reasons for the lack of benefit observed in the trial. There were, however, indicators suggesting therapeutic potential in microvascular ischaemic complications associated with peripheral artery disease, with subsequent analysis showing reduction in the incidence of lower extremity ischaemic ulceration or gangrene. Reassurance about the safety of pemafibrate, together with emerging data from PROMINENT and experimental studies, also suggest benefit with pemafibrate in non-alcoholic fatty liver disease (alternatively referred to as metabolic dysfunction-associated steatotic liver disease) and microangiopathy associated with diabetes, which merit further study. [ABSTRACT FROM AUTHOR]

Background: The usefulness of C-reactive protein (CRP) to predict cardiovascular disease (CVD) in type 2 diabetes (T2DM) remains controversial. As many factors linked to obesity can modulate CRP in T2DM, we comprehensively revisited the cardiometabolic phenotype of patients with normal or raised CRP, taking into account the sexual dimorphism of its serum value.Methods: 1005 T2DM patients (651 males, 354 females; macroangiopathy 38%; coronary artery disease 26%; microangiopathy 47%) were divided depending on whether CRP level was ≤ or >3 mg/L. Thirty percent of men (n = 195) and 39% of women (n = 137) had raised CRP. Their cardiometabolic phenotype and presence of micro- and macrovascular complications were compared to those with normal CRP.Results: In both gender, patients with elevated CRP had higher body mass index, waist circumference, fat mass, visceral fat, insulinemia, HbA1c, and lower muscle mass and insulin sensitivity. They had more atherogenic dyslipidemia, higher non-HDL-C and apolipoprotein B100, and more lipoprotein(a) (+59% in men and +38% in women). In both sexes, there was no difference between patients with normal or high CRP regarding overall macroangiopathy (42% vs. 45% [men]; 27% vs. 28% [women]), coronary and peripheral artery disease, or stroke. Only in men, microangiopathy was more prevalent when CRP was raised (61% vs 44%; p < 0.0001).Conclusions: This study shows major sex-related differences in microangiopathies in T2DM patients with high CRP levels. The latter are unrelated to prevalent CVD despite an unfavorable metabolic phenotype. By contrast, increased CRP may represent an extended biomarker of microvascular risk in men with T2DM. [ABSTRACT FROM AUTHOR]

Background: Older patients with type 2 diabetes mellitus represent a heterogeneous group in terms of metabolic profile. It makes glucose-lowering-therapy (GLT) complex to manage, as it needs to be individualised according to the patient profile. This study aimed to identify and characterize subgroups existing among older patients with diabetes. Methods: Retrospective observational cohort study of outpatients followed in a Belgian diabetes clinic. Included participants were all aged ≥75 years, diagnosed with type 2 diabetes, Caucasian, and had a Homeostasis Model Assessment (HOMA2). A latent profile analysis was conducted to classify patients using the age at diabetes diagnosis and HOMA2 variables, i.e. insulin sensitivity (HOMA2%-S), beta-cell-function (HOMA2%-β), and the product between both (HOMA2%-βxS; as a measure of residual beta-cell function). GLT was expressed in defined daily dose (DDD). Results: In total, 147 patients were included (median age: 80 years; 37.4% women; median age at diabetes diagnostic: 62 years). The resulting model classified patients into 6 distinct cardiometabolic profiles. Patients in profiles 1 and 2 had an older age at diabetes diagnosis (median: 68 years) and a lesser decrease in HOMA2%-S, as compared to other profiles. They also presented with the highest HOMA2%-βxS values. Patients in profiles 3, 4 and 5 had a moderate decrease in HOMA2%-βxS. Patients in profile 6 had the largest decrease in HOMA2%-β and HOMA2%-βxS. This classification was associated with significant differences in terms of HbA1c values and GLT total DDD between profiles. Thus, patients in profiles 1 and 2 presented with the lowest HbA1c values (median: 6.5%) though they received the lightest GLT (median GLT DDD: 0.75). Patients in profiles 3 to 5 presented with intermediate values of HbA1c (median: 7.3% and GLT DDD (median: 1.31). Finally, patients in profile 6 had the highest HbA1c values (median: 8.4%) despite receiving the highest GLT DDD (median: 2.28). Other metabolic differences were found between profiles. Conclusions: This study identified 6 groups among patients ≥75 years with type 2 diabetes by latent profile analysis, based on age at diabetes diagnosis, insulin sensitivity, absolute and residual β-cell function. Intensity and choice of GLT should be adapted on this basis in addition to other existing recommendations for treatment individualisation. [ABSTRACT FROM AUTHOR]

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk. [ABSTRACT FROM AUTHOR]

The diagnosis of cystic fibrosis-related diabetes (CFRD) faces several challenges. We propose a novel screening algorithm to alleviate the burden of cystic fibrosis (CF). Through a retrospective cross-sectional single-centre study, HbA1c and HOMA2 indices were assessed in multiple models as alternative diagnostic tools from OGTT data. We sought to establish specific thresholds for CFRD screening with oral glucose tolerance test (OGTT) as gold standard. We evaluated various straightforward or sequential approaches, in terms of diagnostic accuracy while also quantify the potential reduction in OGTTs through these different methods. HOMA indices were recovered in 72 patients. We devised a composite index that combines HbA1c and HOMA-B: Diabetes Predicting Index in cystic fibrosis (DIPIc) = (HbA1c(%) × 3.455) – (HOMA-B(%) × 0.020) – 19.294. This index yields the highest screening accuracy according to receiver-operating characteristics curves. Using a stepwise algorithm that incorporates DIPIc decreases the requirement for annual OGTTs. A CFRD exclusion cutoff less than −1.7445 (sensitivity 98 %), in conjunction with a CFRD diagnostic threshold greater than 0.4543 (specificity 98 %) allows for 71 % OGTT sparing. The composite index DIPIc is a suitable, less invasive screening method for CFRD, which enables to avoid many OGTTs. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a study on the variability of insulin sensitivity indices (ISIs) result based on various insulin immunoassays.

Coronary artery disease (CAD) is a major cardiovascular (CV) complication in type 2 diabetes (T2DM) populations with metabolic syndrome (MS) phenotype, while T2DM is increasingly recognized as a major co-morbidity in CAD patients. It is not established whether those overlapping populations share a similar macrovascular phenotype. We therefore compared the clinical and biochemical characteristics of patients with both T2DM and CAD followed either in the cardiac or diabetes out/inpatient clinics. From a cohort of 385 patients with T2DM and CAD, we analyzed 314 patients followed in the cardiology clinic (CC) and compared this group to 71 patients followed in the diabetes clinic (DC) from the same university hospital. Data are expressed as means (1SD) or proportions (%). Age, sex, family CV history, blood pressure, smoking exposure and aspirin use were similar in both groups, as were BMI, abdominal circumference and MS (ATP III definition) prevalence. MS severity was lesser in CC, 38% of whom scored at the lowest (3/5) category vs. 18% in DC (p<0.05). The CC group was less often treated with statins/fibrates (44/13 vs. 63/40%), glitazones (2 vs. 10%) and insulin (20 vs. 60%), and more often with beta-blockers (74 vs. 61%) as compared to the DC group (all p<0.05). HbA1c and serum creatinine were higher in DC (8.0 vs. 7.4% and 1.38 vs. 1.12 mg/dL respectively; p<0.05). LDL-C was lower in DC (102 vs. 116 mg/dL), while triglycerides were higher (211 vs. 174 mg/dL; p<0.05). BNP [27 (45) vs. 16 (15)] and Big-ET-1 [9.3 (4.8) vs. 7.7 (2.9)] were higher in CC than in DC (p<0.05). Peripheral artery disease was more prevalent in DC as compared to CC (28 vs. 17%; p<0.05), as a result of a markedly higher stroke prevalence recorded in DC (24 vs. 8% in CC; p<0.001). Our results indicate that patients with both CAD and T2DM followed in the diabetes clinic have a markedly higher stroke prevalence than those followed in the cardiology clinic, despite similar conventional risk factors such as BMI, blood pressure, smoking exposure and family CV history. This unexpected and unreported divergence warrants further investigations regarding established and putative stroke determinants in these seemingly overlapping populations. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Familial hypercholesterolaemia (FH) is an autosomal dominant lipoprotein disorder characterized by significant elevation of low-density lipoprotein cholesterol (LDL-C) and markedly increased risk of premature cardiovascular disease (CVD). Because of the very high coronary artery disease risk associated with this condition, the prevalence of FH among patients admitted for CVD outmatches many times the prevalence in the general population. Awareness of this disease is crucial for recognizing FH in the aftermath of a hospitalization of a patient with CVD, and also represents a unique opportunity to identify relatives of the index patient, who are unaware they have FH. This article aims to describe a feasible strategy to facilitate the detection and management of FH among patients hospitalized for CVD. Methods A multidisciplinary national panel of lipidologists, cardiologists, endocrinologists and cardio-geneticists developed a three-step diagnostic algorithm, each step including three key aspects of diagnosis, treatment and family care. Results A sequence of tasks was generated, starting with the process of suspecting FH amongst affected patients admitted for CVD, treating them to LDL-C target, finally culminating in extensive cascade-screening for FH in their family. Conceptually, the pathway is broken down into 3 phases to provide the treating physicians with a time-efficient chain of priorities. Conclusions We emphasize the need for optimal collaboration between the various actors, starting with a "vigilant doctor" who actively develops the capability or framework to recognize potential FH patients, continuing with an "FH specialist", and finally involving the patient himself as "FH ambassador" to approach his/her family and facilitate cascade screening and subsequent treatment of relatives. Highlights • A strategy to facilitate the detection and management of FH among patients hospitalized for CVD. [ABSTRACT FROM AUTHOR]

Background: Although there are already success stories, population health management in Belgium is still in its infancy. A health system transformation approach such as population health management may be suited to address the public health issue of atherosclerotic cardiovascular disease, as this is one of the main causes of mortality in Belgium. This article aims to raise awareness about population health management in Belgium by: (a) eliciting barriers and recommendations for its implementation as perceived by local stakeholders; (b) developing a population health management approach to secondary prevention of atherosclerotic cardiovascular disease; and (c) providing a roadmap to introduce population health management in Belgium. Methods: Two virtual focus group discussions were organized with 11 high-level decision makers in medicine, policy and science between October and December 2021. A semi-structured guide based on a literature review was used to anchor discussions. These qualitative data were studied by means of an inductive thematic analysis. Results: Seven inter-related barriers and recommendations towards the development of population health management in Belgium were identified. These related to responsibilities of different layers of government, shared responsibility for the health of the population, a learning health system, payment models, data and knowledge infrastructure, collaborative relationships and community involvement. The introduction of a population health management approach to secondary prevention of atherosclerotic cardiovascular disease may act as a proof-of-concept with a view to roll out population health management in Belgium. Conclusions: There is a need to instill a sense of urgency among all stakeholders to develop a joint population-oriented vision in Belgium. This call-to-action requires the support and active involvement of all Belgian stakeholders, both at the national and regional level. [ABSTRACT FROM AUTHOR]

Nebivolol is a BP-lowering drug that combines β-blocking with vascular NO-release, ensuring peripheral vasodilation with lesser peripheral resistance. This unique dual action provides higher intra-class tolerability, making it a suitable choice for hypertensive subjects with type 2 diabetes (T2DM) as mono-or add-on therapy. No assessment is yet available on the potential impact of nebivolol's properties on Quality of Life (QoL), efficacy and tolerability in non-diabetic and in T2DM hypertensive subjects. The QoLaN Study included 1620 poorly-controlled hypertensive subjects (followed by 133 GPs) in whom nebivolol was introduced as monotherapy (n=587), add-on (n=460) or switch (n=421), or compared with a control group (n=152). The multicentre, prospective, open trial had a 2-month mean follow-up and this analysis of QoLaN compares 370 non-diabetic (NDH) and 90 T2DM (T2H) hypertensive subjects in whom nebivolol was introduced as add-on therapy, with graded questionnaire's assessment of QoL (at entry and after 2 months) related to modifiable items potentially affected by BP-lowering therapy. NDH and T2H had similar age (64 (12) years; mean (ISD)), age at hypertension diagnosis, sex ratio, systolo/diastolic BP values pre-nebivolol (NDH : 162/96 (16/8) vs. 162/95 (14/9) mm Hg in T2H) and post-nebivolol BP decrements (at 2-month : NDH: -23/-13 (16/8) vs. -25/-14 (15/9) mm Hg in T2H). Both in NDH and T2H groups, the following items were favorably-unfavorably rated (% of subjects at 2-month): headache: 39-10 (NDH) and 43-11 (T2H); fatigue: 59-6 (NDH) and 51-13 (T2H); coughing: 28-6 (NDH) and 11-9 (T2H); peripheral edema: 19-8 (NDH) and 30-11 (T2H); dyspnoea: 18-6 (NDH) and 9-11 (T2H); satisfaction with sexual life: 28-12 (NDH) and 33-19 (T2H); satisfaction with professional life: 30-15 (NDH) and 39-20 (T2H); and satisfaction with current BP therapy: 58-14 (NDH) and 47-15 (T2H). The QoLaN study demonstrates that adding nebivolol in GP practices to poorly-controlled hypertensive subjects brings about a marked improvement in BP values, both in non-diabetic and in T2DM subjects, alongside beneficial shifts in the ratings of a QoL questionnaire pertaining to modifiable items affected by BP-lowering therapy. [ABSTRACT FROM AUTHOR]

The aim of the study is (1) to determine the clinical phenotype of adolescent and adult patients with cystic fibrosis (CF), according to heterozygnsity or homozygosity for CFTR gene ΔF 508 mutation, and (2) to analyse their characteristics according to glucose tolerance status. Seventy-six CF patients with CFTR gene ΔF 508 mutation including 33 heterozygous and 43 homozygous individuals were studied. They were stratified according to normal (NGT, n = 51) or abnormal (AGH; prediabetes [IFG-IGT] or diabetes, n = 25) glucose homeostasis status. We measured using HOMA (Homeostasis Model Assessment) the β-cell function (HOMA-B) and insulin sensitivity (HOMA-S), allowing for defining a [BxS] product. Pancreatic exocrine insufficiency was inferred from requirements for oral pancreatic supplementation. Clinical effects of insulin therapy on weight and lung function were also recorded. An AGH was observed in 24 and 40% of heterozygous and homozygous subjects respectively. Patients with AGH were older than those with NGT (29 ± 10 vs. 23 ± 8 years, mean ± SD; p=8.006) and their B function was lower (93 ± 49 vs. 125 ± 51%, p=0.011). HOMA-S values were comparable in NGT and AGH individuals. A lower hyperbolic BxS product was observed in AGH, although non-significant when adjusted for error propagation. Pancreatic insufficiency was observed in 52 and 100% of ΔF 508 hetero- and homozygous patients respectively, (p=0.001). In subjects With AGH, HbA[sub 1C] was lowered from 7,3 ± 1,3 to 6,8 ± 1,2% after insulin therapy. This treatment also significantly improved nutritional status (p=0.030) and lung function (p=0.046). Prediabetes and diabetes represent frequent co-morbidities in young adults who carry the CFTR gene ΔF 508 mutation in the homozygous or heterozygous state. Impairment of insulin secretion, as shown by HOMA, is a hallmark of this condition, in the absence of common-type insulin resistance. Given the high prevalence of abnormal glucose tolerance, screening for (pre) diabetes is mandatory. Insulin supplementation in diabetic CFTR gene ΔF 508 subjects seems a rational therapy based on pathophysiological mechanism as well as on response to therapy. [ABSTRACT FROM AUTHOR]