Hidden chronic metabolic acidosis of diabetes type 2 (CMAD): Clues, causes and consequences.

Interpretation of existing data revealed that chronic metabolic acidosis is a pathognomic feature for type 2 diabetes (T2D), which is described here as "chronic metabolic acidosis of T2D (CMAD)" for the first time. The biochemical clues for the CMAD are summarised in the following; low blood bicarbonate (high anionic gap), low pH of interstitial fluid and urine, and response to acid neutralization, while the causes of extra protons are worked out to be; mitochondrial dysfunction, systemic inflammation, gut microbiota (GM), and diabetic lung. Although, the intracellular pH is largely preserved by the buffer system and ion transporters, a persistent systemic mild acidosis leaves molecular signature in cellular metabolism in diabetics.

Sex-Biased Expression of Genes Allocated in the Autosomal Chromosomes: Blood LC-MS/MS Protein Profiling in Healthy Subjects.

Background: Sex and gender have a large impact in human health and disease prediction. According to genomic/genetics, men differ from women by a limited number of genes in Y chromosome, while the phenotypes of the 2 sexes differ markedly.

Methods: In this study, serum samples from six healthy Bahraini men and women were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS).

Plasma IL-6, TREM1, uPAR, and IL6/IL8 biomarkers increment further witnessing the chronic inflammation in type 2 diabetes.

Objectives: Type 2 diabetes (T2D) is known to be associated with chronic inflammation, but the inflammatory regulators/markers are not exactly defined and the link between them remains undetermined. The objective of this study is to identify these markers by testing traditional (IL6 & IL8) and non-traditional (TREM1 & uPAR) inflammatory markers.

Methods: Data and blood samples were obtained from 114 T2D and 74 non-diabetic Kuwaiti subjects attending health facilities in Kuwait.

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Background: Although obesity and T2DM comorbidity is too frequent, the molecular basis of diabetic obesity is largely unexplained and barely investigated.

Materials: Cross-sectional studies were conducted in Kingdom of Saudi Arabia (KSA) in 2013 and Kuwait in 2019. Fasting blood samples were obtained from a total of 216 T2DM patients (104 from KSA) and 193 nondiabetic subjects (93 from KSA) after their consents.

Diabetic sarcopenia: metabolic and molecular appraisal.

Myopathy is the missing slot from the routine clinical checkup for diabetic complications. Similarly, its pathophysiological, metabolic, and molecular bases are insufficiently explored. In this review, the above issues are highlighted with a focus on skeletal muscle atrophy (also described as diabetic sarcopenia), in contrast to the normal histological, physiological, and molecular features of the muscles.

Diabetes mellitus tendino-myopathy: epidemiology, clinical features, diagnosis and management of an overlooked diabetic complication.

Tendino-myopathy, an unexplored niche, is a non-vascular unstated T2DM complication, which is largely disregarded in clinical practice, thus, we aim to explore it in this review. Literature search using published data from different online resources. Epidemiologically, reported prevalence varies around 10-90%, which is marked variable and unreliable.

Hormonal and metabolic profiles of obese and nonobese type 2 diabetes patients: implications of plasma insulin, ghrelin, and vitamin D levels.

Unlabelled: Type 2 diabetes (T2D) is associated with obesity whereas loss of weight is a feature of the disease; however, the two states are not mutually exclusive. Obesity is linked with changes in hormonal activity and overall body metabolism.

Materials And Methods: In this study, 408 T2D patients were recruited in three distinct studies conducted in Bahrain, Saudi Arabia, and Kuwait in three different intervals between 2001 and 2019.

Analogous telomeres shortening and different metabolic profile: hypertension versus hypertension/type 2 diabetes mellitus comorbidity.

Background: Eukaryotes chromosomal ends are capped and protected by telomeres, which are noncoding DNA repeats synthesized by telomerase enzyme. The telomerase enzyme is a nucleoprotein encoded by and genes. Naturally, the length of the telomeres shortens with each cell cycle but the shortening is fastened in certain age-related diseases like hypertension (HTN) and type 2 diabetes mellitus (T2DM).

The influence of TERC, TERT and ACYP2 genes polymorphisms on plasma telomerase concentration, telomeres length and T2DM.

Telomeres are duplex tandem repeats of DNA sequence 5'-TTAGGG-3' at chromosomal ends synthesized by telomerase enzyme (TE). Telomeres length (TL) shortening is associated with age and age-related disorders. Recently, we demonstrated marked leukocytes TL (LTL) shortening in T2DM.

Shortening of the leucocytes' telomeres length in T2DM independent of age and telomerase activity.

Aims: This study aimed to examine the role of plasma telomerase (TE), plasma insulin, patient's age and disease duration in determination of the leucocytes' telomeres length (LTL) in T2DM.

Methods: Blood samples from Kuwaiti patients with T2DM (110) and non-diabetic subjects (94) were analyzed by SYBR Green Quantitative PCR for estimation of the Absolute Human Telomere Length and by ELISA for estimation of the TE activity and insulin level. The body mass index (BMI) and HOMA-IR were calculated.

Gender-Dependent Association of Vitamin D Deficiency with Obesity and Hypercholesterolemia (LDLC) in Adults.

Background: Obesity, dyslipidemia and vitamin D deficiency are growing health problems in the Arabian Gulf region. Their association with each other is yet to be clarified.

Methods: Three-hundred and fourteen Bahraini adults, 164 males and 150 females comparable in median age (34.

Association of TATA box-binding protein-associated factor RNA polymerase I subunit C (TAF1C) with T2DM.

Proteins differential expression in type 2 diabetes mellitus (T2DM) can be due to etiological factors or pathological changes, such proteins can be utilized as biomarkers. Identification of a marker protein out of thousands became a feasible task during the proteomics era by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, blood samples were obtained from 80 Bahraini subjects with and without T2DM, a subset was used for proteomic analysis by LC-MS/MS, while all samples were used for ELISA analysis of 3 proteins, TATA-box binding protein-associated factor RNA polymerase-1-C (TAF1C), ceruloplasmin (CERP) and fibronectin (FN).

LC‑MS/MS proteomic analysis revealed novel associations of 37 proteins with T2DM and notable upregulation of immunoglobulins.

Type 2 diabetes mellitus (T2DM) is a disease associated with a number of metabolic disturbances, including protein metabolism. In the present study, blood samples were obtained from Bahraini subjects, including 6 patients with T2DM and 6 age‑ and sex‑matched, non‑diabetic, healthy controls. Depleted and non‑depleted sera were prepared from the collected blood, and the global protein expression changes were evaluated by liquid chromatography tandem mass spectrometry.

Leu72Met and Other Intronic Polymorphisms in the GHRL and GHSR Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population.

Background: Ghrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associations raise the issue of 'which SNPs in which populations.

Independent associations of polymorphisms in vitamin D binding protein (GC) and vitamin D receptor (VDR) genes with obesity and plasma 25OHD3 levels demonstrate sex dimorphism.

We investigated a possible association between polymorphisms in vitamin D binding protein (GC) and vitamin D receptor (VDR) genes and obesity in Bahraini adults. For this purpose, 406 subjects with varying body mass indexes (BMIs) were selected. Plasma levels of 25-hydroxyvitamin D3 (25OHD3) were measured by chemiluminescence immunoassay.

Lack of significant influence for FcγRIIa-RH131 or hemoglobin AA/AS polymorphisms on immunity and susceptibility to uncomplicated malaria and existence of marked linkage between the two polymorphisms in Daraweesh.

Malaria signature on human genome is marked by several gene polymorphisms. HemoglobinAS (HbAS) is known to protect against severe malaria, but barely proved to protect against uncomplicated malaria (UM). Similarly, the influence of FcγRIIa-RH131 polymorphism on malaria is controversial.

Associations of multi-locus polymorphisms in an immune network with susceptibility to uncomplicated Plasmodium falciparum malaria in Daraweesh village, Eastern Sudan.

Susceptibility to uncomplicated malaria (UM), as to other forms of the disease, is genetically determined. Over 9-years of clinical and parasitological follow up of inhabitants of Daraweesh, in Eastern Sudan, the relative susceptibility to UM was estimated in terms of number of episodes experienced by each individual. Previously, we reported that the levels of IgG2 and IgG3 to Pf332-C231 malaria antigen are negatively correlated with number of malaria episodes.

Validation of PCR for detection and characterization of parasitaemia in massive splenomegaly attributed clinically to malaria infection.

In this study, 101 patients with massive splenomegaly (MS) and 41 with moderate splenomegaly (MoS) from Kassala, Eastern Sudan, were included. The patients were recruited during a peak and the end of a malaria season and during a dry season between 2007 and 2008. Based on clinical findings and exclusion of other causes of MS, the former patients were presumed to be infected with malaria parasite; thus, the condition was termed as massive malarial splenomegaly (MMS).

Raised plasma insulin level and homeostasis model assessment (HOMA) score in cerebral malaria: evidence for insulin resistance and marker of virulence.

Objective: To study the glycaemic profile of patients with severe malaria (SM).

Methods: For this purpose, 110 SM patients were recruited. Pre-treatment random blood glucose and plasma insulin were measured in a subset of donors.

Towards a noninvasive approach to malaria diagnosis: detection of parasite DNA in body secretions and surface mucosa.

Invasive procedures for diagnostic or therapeutic purposes bear a relative risk of transmission of serious blood-borne infectious disease. In this study, a noninvasive approach to malaria diagnosis using polymerase chain reaction (PCR) for the detection of parasite DNA in saliva, buccal mucosa and urine (alternative samples) was examined. Saliva, buccal mucosa and urine samples were collected simultaneously with blood samples from 93 patients with microscopically confirmed Plasmodium falciparum infection.

Prospects of intermittent preventive treatment of adults against malaria in areas of seasonal and unstable malaria transmission, and a possible role for chloroquine.

Chloroquine (CQ) is outmoded as an antimalarial drug in most of the malarial world because of the high resistance rate of parasites. The parasite resistance to CQ is attributed to pfcrt/pfmdr1 gene mutations. Recent studies showed that parasites with mutations of pfcrt/pfmdr1 genes are less virulent, and that those with dhfr/dhps mutations are more susceptible to host immune clearance; the former and latter mutations are linked.

Clustering of malaria treatment failure (TF) in Daraweesh: hints for host genetic susceptibility to TF with emphasis on immune-modulating SNPs.

In malaria, drug resistance and treatment failure (TF) are not synonymous, although are escalating together. Over 9 years of surveillances for malaria morbidity and TF in Daraweesh village in eastern Sudan (1991-2004), 136 donors (15-78 years) from 43 households, treated for 278 malaria episodes and had experienced 46 incident of TF, were included in this study. Blood obtained from the donors in 2005, was used for measurement of IgG subclasses against Pf332-C231 antigen and GM/KM allotyping and for genotyping of the donors for; FcgammaRIIA 131 (HH, RH, RR), CRP 286 (C View Article and Find Full Text PDF

Age-dependent association between IgG2 and IgG3 subclasses to Pf332-C231 antigen and protection from malaria, and induction of protective antibodies by sub-patent malaria infections, in Daraweesh.

The certainty of the protective role of acquired immunity in malaria is the major drive for malaria vaccine development. In this study, we measured the levels of total IgG and IgG subclasses to four candidate malaria vaccine antigens; MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231, in plasma obtained from a cohort of 136 donors from Daraweesh in Sudan. The cohort was followed for malaria infection for 9 years.