Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus.

Background: The role of the immune system in insulin resistance associated with type 2 diabetes has been suggested. Objectives: We assessed the profile of Th1/Th2 cytokines along with the frequencies of immune cells in insulin-treated type 2 diabetic patients (T2DP). Methods: 45 T2D patients and 43 age-matched healthy subjects were selected. Serum concentrations of T-helper type 1 (Th1) and Th2 cytokines and the frequencies of innate and adaptive immunity cells were assessed. Results: T2DP were hyperglycemic and showed high level of insulin, normal levels of triglycerides and total-cholesterol and without any change in HDL-cholesterol.Compared to healthy subjects, T2DP exhibited significant decreased frequencies of neutrophils, without any change in monocytes, eosinophils and natural killer cells. The percentages of total lymphocytes (CD3+) and CD8+-T-cells decreased whereas those of regulatory T-cells increased without any change in CD4+ T-cells in T2DP. Interestingly, the frequencies of effector CD4+-T and B-cells increased in T2DP. Serum concentrations of IL-2, IFN-\u3b3 and IL-4 decreased while IL-10 significantly enhanced in T2DP, suggesting a differentiation of CD4+T helper cells towards IL-10-producing- Teff-cells in these patients. Conclusion: Insulin-treated type 2 diabetes is associated with anti-inflammatory profile consistent with differentiation of CD4+-Th-cells towards IL-10-producing-Teff-cells, concomitant with increased frequencies of Treg and B-cells, and this may probably offer prevention against certain infections or autoimmune/inflammatory diseases

GAD65 antibody prevalence and association with c-peptide, HLA class II alleles in Beninese patients with type 1 diabetes

Background: Antibodies to glutamic acid decarboxylase and particularly their isoforms in 65 kDa are one of markers for the diagnosis of the type 1 diabetes (T1D). The aim of this study is to assess the prevalence of GAD65 antibodies (GAD65Ab) and investigate the association of GAD65Ab with C-peptide values, HLA Class II alleles genotyping. The diagnosis of T1D was set up according to American Diabetes Association criteria.Methods: Radioimmunoassay was used to determine the GAD65Ab and C-peptide values. Class II HLA genotyping was performed in 51 patients with T1D and 51 healthy unrelated as control by using the PCR-SSP method. The sensitivity and specificity of the tests were calculated by standard formula.Results: Result revealed that GAD65Ab were present in 74.5% (38/51) of the patients with T1D. There was no significant difference between the positivity or the negativity of GAD65Ab and gender, onset and duration of diabetes, frequencies of HLA-DR4, HLA-DR3-DR4, HLA-DQB1*0201. However, GAD65Ab values are linked to C-peptide concentration (χ2 =15.73, P=0.0001), the presence of HLA-DR3 (χ2 =9.75, P= 0.002), HLA-DQA1*0501 (χ2 =4.09, P= 0.043) alleles. The GAD65Ab test sensitivity and specificity were 74.5% and 94.1%, respectively. The C-peptide test showed a sensitivity around 82.4 % and 86.3 % for the specificity.Conclusions: GAD65Ab showed to be a valuable early predictive marker and is associated with the risk to develop of T1D

Prévalence et déterminants de l’albuminurie dans le diabète de type 2 chez le sujet noir au Sud du Bénin

Objectif: Décrire les facteurs déterminants de l’albuminurie chez le diabétique de type 2.Méthodes: Nous avons mené une étude transversale, prospective à visée descriptive et analytique. Elle s’est déroulée sur une période de 06 mois de février à Août 2014. Ont été inclus les patients diabétiques de type 2 suivis par un spécialiste et ayant fait les dosages nycthéméraux de l’albumine urinaire par la méthode immunoturbidimétrique. Ces dernières sont considérées comme positives à partir de 30 mg/24 h d’albuminurie. La régression logistique, en analyse multivariée, a permis de mesurer l’association entre la survenue de l’albuminurie et ses déterminants.Résultats: Cent quatre-vingt-un (181) patients étaient retenus, 86 présentaient une albuminurie positive (soit 47.5%) avec une sex-ratio de 0,7. L’âge variait de 19 à 85 ans. L’IMC variait entre 18.9 et 56.0 kg/m². L’albuminurie positive chez les patients ayant un diabète déséquilibré, était de 57.4% contre 32.9% des diabétiques équilibrés (p = 0.001). L’albuminurie positive chez les patients hypertendus était de 65.2% contre 36.6% diabétiques normotendus (p < 0.001). L’hypercholestérolémie totale était associée à une albuminurie positive (p = 0.04). L’ancienneté du diabète était également associée à une l’albuminurie positive (p = 0.01).Conclusion: L’hypertension artérielle, l’hypercholestérolémie, l’équilibre du diabète et l’ancienneté du diabète jouent un rôle important dans la survenue de l’albuminurie chez le diabétique de type 2. Un contrôle strict de ces déterminants s’avère indispensable.Objective: To describe albuminuria causal factors among type 2 diabetes patients.Methods: We carried out a cross-sectional retrospective study aimed at describing and analyzing the subject matter. It was conducted over a six-month period from February to August 2014. Type 2 diabetic patients regularly seen by a specialist who underwent immunoturbidimetric assay of urine albumin were included in the study. It was considered positive for albuminuria above 30 mg/24h. The multivariate logistic regression analysis enabled us to measure the association between albuminuria and its determinants.Results: One hundred and eighty one (181) patients were selected, 86 had positive albuminuria (47.5%) and the sex ratio was recorded at 0.7. Age ranged from 19 to 85 years. BMI ranged from 18.9 to 56.0 kg/m². Positive albuminuria among uncontrolled diabetes patients represented 57.4% against 32.9% controlled diabetes patients (p = 0.001). Positive albuminuria among hypertensive patients was 65.2% against 36.6% in normotensive diabetic patients (p < 0.001). Hypercholesterolemia was associated with positive albuminuria (p = 0.04). Diabetes seniority was also associated with positive albuminuria (p = 0.01).Conclusions: Blood pressure, hypercholesterolemia, the control of diabetes and duration of diabetes all played a significant role in occurrence of albuminuria among type 2 diabetic patients. It is important to carry out a thorough check on these determinants.Objectif                                                                                                           Décrire les facteurs déterminants de l’albuminurie chez le diabétique de type 2.Patients et MéthodesNous avons mené une étude transversale, prospective à visée descriptive et analytique. Elle s’est déroulée sur une période de 06 mois de février à Août 2014. Ont été inclus les patients diabétiques de type 2 suivis par un spécialiste et ayant fait les dosages nycthéméraux de l’albumine urinaire par la méthode immunoturbidimétrique. Ces dernières sont considérées comme positives à partir de 30 mg/24 h d’albuminurie.La régression logistique, en analyse multivariée, a permis de mesurer l’association entre la survenue de l’albuminurie et ses déterminants.RésultatsCent quatre-vingt-un (181) patients étaient retenus, 86 présentaient une albuminurie positive (soit 47,5%) avec une sex-ratio de 0,7. L’âge variait de 19 à 85 ans. L’IMC variait entre 18,93 et 56,01 kg/m².L’albuminurie positive chez les patients ayant un diabète déséquilibré, était de 57,4% contre 32,9% des diabétiques équilibrés. (p = 0,001)L’albuminurie positive chez les patients hypertendus était de 65,2% contre 36,6% diabétiques normotendus. (p = 0,000)L’hypercholestérolémie totale était associée à une albuminurie positive. (p = 0,04)L’ancienneté du diabète était également associée à une l’albuminurie positive. (p = 0,01) Conclusion L’hypertension artérielle, l’hypercholestérolémie, l’équilibre du diabète et l’ancienneté du diabète jouent un rôle important dans la survenue de l’albuminurie chez le diabétique de type 2. Un contrôle strict de ces déterminants s’avère indispensabl

Growth factor concentrations and their placental mRNA expression are modulated in gestational diabetes mellitus: possible interactions with macrosomia

<p>Abstract</p> <p>Background</p> <p>Gestational diabetes mellitus (GDM) is a form of diabetes that occurs during pregnancy. GDM is a well known risk factor for foetal overgrowth, termed macrosomia which is influenced by maternal hypergycemia and endocrine status through placental circulation. The study was undertaken to investigate the implication of growth factors and their receptors in GDM and macrosomia, and to discuss the role of the materno-foeto-placental axis in the <it>in-utero </it>regulation of foetal growth.</p> <p>Methods</p> <p>30 women with GDM and their 30 macrosomic babies (4.75 ± 0.15 kg), and 30 healthy age-matched pregnant women and their 30 newborns (3.50 ± 0.10 kg) were recruited in the present study. Serum concentrations of GH and growth factors, <it>i.e</it>., IGF-I, IGF-BP3, FGF-2, EGF and PDGF-B were determined by ELISA. The expression of mRNA encoding for GH, IGF-I, IGF-BP3, FGF-2, PDGF-B and EGF, and their receptors, <it>i.e</it>., GHR, IGF-IR, FGF-2R, EGFR and PDGFR-β were quantified by using RT-qPCR.</p> <p>Results</p> <p>The serum concentrations of IGF-I, IGF-BP3, EGF, FGF-2 and PDGF-B were higher in GDM women and their macrosomic babies as compared to their respective controls. The placental mRNA expression of the growth factors was either upregulated (FGF-2 or PDGF-B) or remained unaltered (IGF-I and EGF) in the placenta of GDM women. The mRNA expression of three growth factor receptors, <it>i.e</it>., IGF-IR, EGFR and PDGFR-β, was upregulated in the placenta of GDM women. Interestingly, serum concentrations of GH were downregulated in the GDM women and their macrosomic offspring. Besides, the expression of mRNAs encoding for GHR was higher, but that encoding for GH was lower, in the placenta of GDM women than control women.</p> <p>Conclusions</p> <p>Our results demonstrate that growth factors might be implicated in GDM and, in part, in the pathology of macrosomia via materno-foeto-placental axis.</p

Prevalence and Risk Factors of Diabetes Mellitus in the Adult Population of Porto-Novo (Benin)

Introduction: The aim of this study was to determine the prevalence and risk factors of diabetes mellitus in the adult population of Porto-Novo. Methods: A cross-sectional study with random sampling, stratified cluster, was used. Fasting blood glucose was measured in capillary blood (Accu-Chek Active). Diabetes mellitus was defined as fasting glucose ≥ 1.26 g/L, and fasting hyperglycemia in non-diabetic fasting glucose ≥ 1.10 and < 1.26 g/L. Results: The survey involved 240 individuals. The sex ratio was 0.48. The mean age was 46 ± 13 years (range 25 - 80 years). The prevalence of hyperglycemic patients was 7.9%. The prevalence of diabetes was 6.7%, including 3.3% of unknown diabetes, half of diabetics. The prevalence of fasting hyperglycemia without diabetes was 1.2%. The risk factors for diabetes type 2 onset were a family history of diabetes (p = 0.017), older age (p = 0.003), hypertension (p = 0.005) and abdominal obesity (NCEP: p = 0.044; FID: p = 0.001). Conclusion: These high figures confirm the increasing prevalence of diabetes mellitus in Benin, documented in many developing countries

Impact cardiovasculaire des incrétino-mimétiques chez le diabétique de type 2 : le point en 2015

Les incrétino-mimétiques (agonistes du récepteur du glucagon-like peptide-1 [GLP-1] et inhibiteurs de la dipeptidylpeptidase IV [DPP-4]) occupent aujourd’hui une place importante dans la stratégie de traitement du diabète de type 2 (DT2). Sachant le risque élevé de complications cardiovasculaires dans le DT2, il est essentiel pour les cliniciens de s’assurer de la sécurité cardiovasculaire de ces deux nouvelles classes de médicaments. Le but de cet article est de proposer, sur base d’une revue exhaustive de la littérature, un état des lieux des effets cardiovasculaires des agonistes du récepteur du GLP-1 et des inhibiteurs de la DPP-4. À ce stade de nos connaissances, la littérature scientifique suggère, globalement, une sécurité cardiovasculaire. Cela étant, les études à long terme devront le confirmer et, en particulier, préciser le risque éventuel de décompensation cardiaque sous inhibiteurs de la DPP-4.[Collateral cardiovascular effects of incretinomimetics in patients with type 2 diabetes: State of the art in 2015] Incretinomimetics (GLP-1 receptor agonists and DPP-4 inhibitors) are nowadays an important therapeutic approach in patients with type 2 diabetes (T2D). In view of the increased risk of cardiovascular morbimortality in T2D, it is essential for clinicians to evaluate the safety of these new drugs in this field. The aim of this paper is to review, on the basis of recent scientific literature, cardiovascular effects of GLP-1 receptor agonists and DPP-4 inhibitors. Up to now, experimental and clinical studies suggest rather a cardiovascular safety of these drugs. However, long term well designed studies should confirm this particular aspect and in particular precise if DPP-4 inhibitors are associated or not with an increased risk of congestive heart failure

Baseline diabetes as a way to predict CV outcomes in a lipid-modifying trial: A meta-analysis of 330,376 patients from 47 landmark studies

Background: Diabetes is a major cardiovascular risk factor. However, its influence on the rate of occurrence of cardiovascular (CV) events during a clinical trial that included a diabetes subgroup has not yet been quantified. Aims: To establish equations relating baseline diabetes prevalence and incident CV events, based on comparator arms data of major lipid-modifying trials. Methods: Meta-analysis of primary outcomes (PO) rates of key prospective trials, for which the baseline proportion of diabetics was reported, including studies having specifically reported CV outcomes within their diabetic subgroups. Results: 47 studies, representing 330,376 patients (among whom 124,115 diabetics), were analyzed as regards the relationship between CV outcomes rates (including CHD) and the number of diabetics enrolled. Altogether, a total of 18,445 and 16,156 events occurred in the comparator and treatment arms, respectively. There were significant linear relationships between diabetes prevalence and both PO and CHD rates (%/year): y = 0.0299*x + 3.12 [PO] (p = 0.0128); and y = 0.0531*x + 1.54 [CHD] (p = 0.0094), baseline diabetes predicting PO rates between 3.12 %/year (no diabetic included) and 6.11 %/year (all patients diabetic); and CHD rates between 1.54 %/year (no diabetic) and 6.85 %/year (all patients diabetic). The slopes of the equations did not differ according to whether they were derived from primary or secondary prevention trials. Conclusions: Absolute and relative CV risk associated with diabetes at inclusion can be readily predicted using linear equations relating diabetes prevalence to primary outcomes or CHD rates

Do high ferritin levels confer lower cardiovascular risk in men with Type 2 diabetes?

Aims High ferritin levels are associated with insulin resistance and liver steatosis, both thought of as emerging cardiovascular risk factors. The association between ferritin and cardiovascular disease is poorly documented in cardiometabolic states with higher cardiovascular risk, such as diabetes and metabolic syndrome. We therefore characterized a cohort of males with Type 2 diabetes mellitus (T2DM) according to ferritin levels and prevalent macroangiopathy. Methods The presence of overall macroangiopathy, peripheral and/or coronary artery disease was documented in 424 consecutive T2DM males, who were divided according to ferritin quartiles (Q) as follows: QI-III, normal ferritin (NF; n = 318), mean +/- 1 sd ferritin 133 +/- 72 ng/ml; and QIV patients, high ferritin (HF; n = 106), ferritin 480 +/- 228 ng/ml. Results Age, age at diabetes diagnosis, smoking, ethanol intake, body mass index, waist circumference, blood pressure and presence of metabolic syndrome did not differ between groups. However, the prevalence of macroangiopathy was unexpectedly much lower in patients with high ferritin, as follows: 25% vs. 43% for overall macroangiopathy; 7% vs. 16% for peripheral artery disease; and 16% vs. 31% for coronary artery disease (P = 0.0009, P = 0.0140 and P = 0.0035, respectively, vs. NF patients). Insulin resistance index and prevalence of liver steatosis were higher in HF compared with NF patients as follows: 2.17% vs. 1.89% and 78% vs. 64% (P = 0.0345 and P = 0.0059, respectively). Liver enzymes (aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase) were significantly higher in HF, by 33%, 42% and 72%, respectively (all P < 0.0002), suggesting a higher prevalence of steatohepatitis. Glycated haemoglobin, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, urate, high-sensitivity C-reactive protein and albuminuria were not different between groups. Conclusions Our results demonstrate that T2DM males with high ferritin levels exhibit a markedly decreased prevalence of macroangiopathy, despite more severe insulin resistance and higher markers of steatohepatitis. High ferritin levels and/or steatosis may thus paradoxically confer a lowered cardiovascular risk in diabetic males

The normal-weight type 2 diabetes phenotype revisited.

BACKGROUND: Type 2 diabetes (T2DM) is associated with obesity, insulin resistance and the metabolic syndrome (MetS). In non-diabetic populations, features of metabolic obesity (MO) are observed in a minority of normal-weight (NW) subjects. The cardiometabolic status of metabolically obese but normal-weight (MONW) individuals has not yet been phenotyped in T2DM. PATIENTS AND METHODS: Prevalence and features of MONW were analyzed in 1244 T2DM patients, in whom MONW was identified as a BMI <25.0 and a MetS score ≥3/5. Among NW (n=262; 21%), those without MetS (n=152; NW-MetS[-]) were compared to NW-MetS[+] (n=110; i.e. 42% of NW and 9% of all T2DM). RESULTS: There were no differences between groups in age; gender; diabetes duration; smoking; BP; and LDL-C. NW-MetS[+] had higher BMI; waist; fat mass; visceral fat; liver steatosis and HbA1c, and lower insulin sensitivity. Non-right-handedness was twice-higher (18%) in NW-MetS[-]. NW-MetS[+] had higher apoB100 and triglycerides, and lower HDL-C and LDL size. Macroangiopathy was present in 39% of NW-MetS[+] vs. 22% of NW-MetS[-], as coronary (23% vs. 14%) or peripheral artery disease (14% vs. 5%) and TIA/stroke (15% vs. 7%). Microangiopathy was present in 54% of NW-MetS[+] vs. 32% of NW-MetS[-], as retinopathy (25% vs. 13%); neuropathy (29% vs. 18%); and albuminuria (39% vs. 20%). CONCLUSIONS: MONW among T2DM represents a significant minority (about 1 in 10). Their cardiometabolic phenotype deserves attention due to multiple comorbidities, including a twice-higher prevalence of micro-/macrovascular damage in patients wrongly perceived at lower risk due to normal BMI. Unexpectedly, non-right-handedness was over-represented among metabolically healthy patient

Fatty liver and atherogenic dyslipidemia have opposite effects on diabetic micro- and macrovascular disease.

BACKGROUND AND AIMS: Non-alcoholic fatty liver (FL) is comorbid with obesity, metabolic syndrome and type 2 diabetes. Atherogenic dyslipidaemia (AD), frequent in FL, is associated with risk of micro- and macrovascular complications. Given the paradoxical ocular protection of FL in T2DM, we studied how FL modulates micro- and macrovascular complications as a function of AD. METHODS: Cross-sectional factorial analysis of 744 diabetic patients in whom FL, identified by ultrasonography, was present in 68%. AD, defined by low HDL-C plus elevated TG, was present in 45%. Four groups were analysed as regards cardiometabolic features, micro-/macroangiopathies, cataract and ocular hypertonia: FL[-]AD[-] (n = 171); FL[-]AD[+] (n = 66); FL[+]AD[-] (n = 235); and FL[+]AD[+] (n = 272). RESULTS: Age, gender and glycemic control were similar across groups. Prevalence of overall macroangiopathy and coronary artery disease were higher in patients with AD, irrespective of FL. Overall macroangiopathy was higher, by 64% in FL[-]AD[+] and by 38% in FL[+]AD[+]. Coronary artery disease was higher, by 128%, in FL[-]AD[+], and by 67%, in FL[+]AD[+]. (Micro)albuminuria was more frequent (+55%) in FL[-] AD[+] compared to FL[-] AD[-]. Retinopathy prevalence was 35% in FL[-], unaffected by AD. Retinopathy frequency was much lower in FL[+], irrespective of AD, decreased by -47% in FL[+]AD[-] and -32% in FL[+]AD[+] (vs. FL[-]AD[-]). Ocular hypertonia was present in 13%, and its prevalence was also markedly lower (-31%) in FL[+]. Cataract frequency was 29%, also lesser in FL[+] (24% vs. 39%), irrespective of AD. CONCLUSIONS: Multi-level eye protection in diabetes is linked to non-alcoholic fatty liver independently of atherogenic dyslipidemia