Maturity-Onset Diabetes of the Young Identified Among Algerian Probands with Early-Onset Diabetes.

AIM: To investigate the prevalence of variants within selected maturity-onset diabetes of the young (MODY)-genes among Algerian patients initially diagnosed with type 1 diabetes (T1D) or type 2 diabetes (T2D), yet presenting with a MODY-like phenotype. METHODS: Eight unrelated patients with early-onset diabetes (before 30 years) and six relatives with diabetes were examined by targeted re-sequencing for variants in genes known to be involved in MODY (HNF1A, GCK, HNF4A, HNF1B, INS, ABCC8, KCNJ1). Clinical data for probands were retrieved from hospital records. RESULTS: A total of 12 variants were identified, of which three were classified as pathogenic and one as a variant of uncertain clinical significance (VUS). Two of the pathogenic variants were found in GCK (p.Gly261Arg and p.Met210Lys, respectively) in one proband each and the remaining pathogenic variant was found in HNF1B (p.Gly76Cys) in a proband also carrying the VUS in HNF1A (p.Thr156Met). CONCLUSION: Variants in known MODY-genes can be the cause of early-onset diabetes in Algerians diagnosed with T1D or T2D among patients presenting with a MODY-like phenotype; thus, genetic screening should be considered.

Metabolic Imbalance and Vitamin D Deficiency in Type 1 Diabetes in the Algerian Population.

BACKGROUND: We aimed to assess Vitamin D levels in patients with Type 1 Diabetes (T1D) and to investigate the correlation between vitamin D and metabolic imbalance. MATERIAL AND METHODS: For our study, we selected thirty-one patients with T1D without complications and fifty-seven healthy controls. Diabetic patients were diagnosed using the criteria of the World Health Organization/American Diabetes Association. Vitamin D, Parathyroid Hormone (PTH), insulin and C peptide assay were performed using chimilunescence. Glucose level, lipid profile, glycated haemoglobin (HbA1c) and ionogram were also analysed. RESULTS: Vitamin D, HbA1c and Gly levels were found to be significant in T1D patients than in controls (P<0.5). However, for PTH, no significant difference was observed (P > 0. 05) and the results show a non-significant difference of total cholesterol potassium, sodium, phosphor and calcium concentration averages. CONCLUSION: Our results indicate that the deficiency of VD is associated with an increased risk of T1DM in Algerian population.

[Incretins-adipocytokines interactions in type 2 diabetic subjects with or without non-alcoholic fatty liver disease: interest of GLP-1 (glucagon-like peptide-1) as a modulating biomarker]. / Interactions incrétines-adipocytokines chez le sujet diabétique de type 2 avec ou sans stéatose hépatique non alcoolique : intérêt du GLP-1 (glucagon-like peptide-1) comme biomarqueur modulateur.

Type 2 diabetes (T2DM) associated with non-alcoholic fatty liver disease (NAFLD) increases cardiovascular risk. Complex and subtle connections are established between hepatic dysfunction and adipose tissue hyperactivity. This relationship is mediated by insulin resistance, dyslipidemia and inflammation. Recently incretins have been involved in this connection including GLP-1 (glucagon-like peptide-1). The aim of this study is to establish interactions between the GLP-1 plasma levels and metabolic syndrome clusters and adipocytokines profile (leptin, adiponectin, resistin, TNFα and IL-6) in diabetic subjects with or without NAFLD. The study was undertaken on 320 adult subjects divided into four groups: NAFLD, DT2, NAFLD+DT2 and control. In all subjects, the metabolic syndrome clusters was investigated according to the NCEP/ATPIII criteria. Insulin resistance was evaluated by the Homa-IR model. The metabolic parameters were determined on Cobas® automated biochemical analysis. The adipocytokines are determined by immunoassay method on Elisa human reader - Biotek ELX 800. The NAFLD has been confirmed by abdominal ultrasound and by histology. Feeding and fasting plasma GLP-1 was assessed by Elisa method. The data revealed that insulin resistance (Homa-IR) is present in all groups. Homa-IR is negatively associated with plasma GLP-1 depletion in the NAFLD, DT2 and NAFLD+DT2 groups. Adiponectin levels are decreased in all groups as for GLP-1. At the opposite, leptin, resistin, TNFα and IL-6 levels show an inverse correlation with GLP-1. This study suggests that plasma GLP-1 can be considered as a transition and evolution biomarker between NAFLD and T2D. GLP-1 accurately reflects metabolic and inflammatory status, both in subjects with NAFLD only or with T2D only, before the diabetes - steatosis stage.

Human Leukocyte Antigens (HLA) Genes Association in Type 1 Diabetic Nephropathy.

BACKGROUND: Diabetic nephropathy is a common worldwide multifactorial disease where involvement of genetic factors is well etablished. The aim of this study was to investigate the HLA genes implication in the development of type 1 diabetic nephropathy. METHODS: We performed a case- control study where one hundred and fifty subjects were examined. Patients were divided in two groups; with and without type 1 diabetic nephropathy. HLA typing was performed using Polymerase Chain Reaction- Sequence Specific Oligonucleotide (PCR- SSO) method. HLA association to clinical phenotype and HLA haplotype analysis was also investigated. RESULTS: HLA B*51 is increased in patients without type 1 diabetic nephropathy (7.14% vs. 0 %, P <0.05, OR= 0), however no other studied alleles seem to have any effect (all P>0.05). Haplotype analysis also does not reveal any significant association, however, A*02-B*18-DRB1*03-DQA1*05- DQB1*03 haplotype shows a tendency to be associated with the development of diabetic nephropathy (P = 0.05). CONCLUSION: These results suggest a protective effect of HLA B*51 allele from type 1 diabetic nephropathy. However, further studies are required in order to clarify its potential implication as a protective marker.

Expert Opinion: Patient Selection for Premixed Insulin Formulations in Diabetes Care.

Premixed insulins are an important tool for glycemic control in persons with diabetes. Equally important in diabetes care is the selection of the most appropriate insulin regimen for a particular individual at a specific time. Currently, the choice of insulin regimens for initiation or intensification of therapy is a subjective decision. In this article, we share insights, which will help in rational and objective selection of premixed formulations for initiation and intensification of insulin therapy. The glycemic status and its variations in a person help to identify the most appropriate insulin regimen and formulation for him or her. The evolution of objective glucometric indices has enabled better glycemic monitoring of individuals with diabetes. Management of diabetes has evolved from a 'glucocentric' approach to a 'patient-centered' approach; patient characteristics, needs, and preferences should be evaluated when considering premixed insulin for treatment of diabetes.Funding: Novo Nordisk, India.

Association of major histocompatibility complex class 1 chain-related gene a dimorphism with type 1 diabetes and latent autoimmune diabetes in adults in the Algerian population.

Major histocompatibility complex class I chain-related gene A (MICA-129) dimorphism was investigated in 73 autoimmune diabetes patients (type 1 diabetes and latent autoimmune diabetes in adults) and 75 controls from Algeria. Only MICA-129 Val allele and MICA-129 Val/Val genotype frequencies were higher among patients than in the control group. Statistical analysis of the estimated extended HLA-DR-DQ-MICA haplotypes shown that individual effects of MICA alleles on HLA-DQ2-DR3-MICA-129 Val/Val and HLA-DQ8-DR4-MICA-129 Val/Val haplotypes were significantly higher in patients than in the control groups. These preliminary data might suggest a relevant role of MICA-129 Val/Val single nucleotide polymorphism (weak/weak binders of NKG2D receptor) in the pathogenesis of T1D and LADA.