BackgroundFoot complications are considered to be a serious consequence of diabetes mellitus, posing a major medical and economical threat. Identifying the extent of this problem and its risk factors will enable health providers to set up better prevention programs. Saudi National Diabetes Registry (SNDR), being a large database source, would be the best tool to evaluate this problem.MethodsThis is a cross-sectional study of a cohort of 62,681 patients aged ≥25 years from SNDR database, selected for studying foot complications associated with diabetes and related risk factors.ResultsThe overall prevalence of diabetic foot complications was 3.3% with 95% confidence interval (95% CI) of (3.16%–3.44%), whilst the prevalences of foot ulcer, gangrene, and amputations were 2.05% (1.94%–2.16%), 0.19% (0.16%–0.22%), and 1.06% (0.98%–1.14%), respectively. The prevalence of foot complications increased with age and diabetes duration predominantly amongst the male patients. Diabetic foot is more commonly seen among type 2 patients, although it is more prevalent among type 1 diabetic patients. The Univariate analysis showed Charcot joints, peripheral vascular disease (PVD), neuropathy, diabetes duration ≥10 years, insulin use, retinopathy, nephropathy, age ≥45 years, cerebral vascular disease (CVD), poor glycemic control, coronary artery disease (CAD), male gender, smoking, and hypertension to be significant risk factors with odds ratio and 95% CI at 42.53 (18.16–99.62), 14.47 (8.99–23.31), 12.06 (10.54–13.80), 7.22 (6.10–8.55), 4.69 (4.28–5.14), 4.45 (4.05–4.89), 2.88 (2.43–3.40), 2.81 (2.31–3.43), 2.24 (1.98–2.45), 2.02 (1.84–2.22), 1.54 (1.29–1.83), and 1.51 (1.38–1.65), respectively.ConclusionsRisk factors for diabetic foot complications are highly prevalent; they have put these complications at a higher rate and warrant primary and secondary prevention programs to minimize morbidity and mortality in addition to economic impact of the complications. Other measurements, such as decompression of lower extremity nerves, should be considered among diabetic patients.

Ghrelin is a 28-amino acid (aa) stomach-derived peptide discovered in 1999 as the endogenous ligand for growth hormone secretagogue-receptor (GHS-R). Ghrelin-producing cells constitute a distinct group of endocrine cells dispersed throughout the gastric mucosa and to a lesser extent in the small intestine and the endocrine pancreas. Ghrelin plasma levels rise during fasting and chronic caloric restriction to stimulate food intake and fat storage and to prevent life-threatening falls in blood glucose. Plasma ghrelin levels decrease after a meal is consumed and in conditions of energy surplus (such as obesity). Ghrelin has emerged as a key player in the regulation of appetite and energy homeostasis. Ghrelin achieves these functions through binding the ghrelin receptor GHS-R in appetite-regulating neurons and in peripheral metabolic organs including the endocrine pancreas. Ghrelin levels are negatively correlated with body mass index (BMI) and insulin resistance. In addition, ghrelin secretion is impaired in obesity and insulin resistance. Several studies highlight an important role for ghrelin in glucose homeostasis. Genetic, immunological, and pharmacological blockade of ghrelin signaling resulted in improved glucose tolerance and insulin sensitivity. Furthermore, exogenous ghrelin administration was shown to decrease glucose-induced insulin release and increase glucose level in both humans and rodents. GHS-R was shown to be expressed in pancreatic β-cells and ghrelin suppressed insulin release via a Ca2+-mediated pathway. In this review, we provide a detailed summary of recent advances in the field that focuses on the role of insulin and insulin resistance in the regulation of ghrelin secretion and on the role of ghrelin in glucose-stimulated insulin secretion (GSIS).

Apelin is a peptide hormone that binds to a class A GPCR (the apelin receptor/APJ) to regulate various bodily systems. Upon signal peptide removal, the resulting 55-residue isoform, proapelin/apelin-55, can be further processed to 36-, 17-, or 13-residue isoforms with length-dependent pharmacological properties. Processing was initially proposed to occur intracellularly. However, detection of apelin-55 in extracellular fluids indicates that extracellular processing may also occur. To test for this, apelin-55 was applied exogenously to HEK293A cells overexpressing proprotein convertase subtilisin kexin 3 (PCSK3), the only apelin processing enzyme identified thus far, and to differentiated 3T3-L1 adipocytes, which endogenously express apelin, PCSK3 and other proprotein convertases. Analysis of culture media constituents from each cell type by high performance liquid chromatography-mass spectrometry and western blot demonstrated a time-dependent decrease in apelin-55 levels. This decrease was partially, but not fully, attenuated by PCSK inhibitor treatment in both cell lines. Comparison of the resulting apelin-55-derived peptide profile between the two cell lines demonstrated distinct processing patterns, with apelin-36 production apparent in 3T3-L1 adipocytes vs. detection of the prodomain of a shorter isoform (likely the apelin-13 prodomain, observed after additional proteolytic processing) in PCSK3-transfected HEK293A cells. Extracellular processing of apelin, with distinct cell type dependence, provides an alternative mechanism to regulate isoform-mediated physiological effects of apelin.

BACKGROUND: Diabetic ketoacidosis (DKA) is well-known to be associated with increased levels of inflammatory markers including cytokines. Interestingly, an elevated white blood count (WBC) has been associated with a higher prevalence of acute and chronic diabetes metabolic complications, including DKA, and micro- and macrovascular complications (Tong et al., 2004; Xu et al., 2013). However, very few studies have looked at the relationship between WBC differential and the severity of DKA. For instance, a study looking at platelet-to-lymphocyte ratio found it to be a significant predictor of mortality in DKA patients admitted to the intensive care unit (Liu et al., 2016). Aim: The goal of the present study is to investigate the relationship between the WBC differential and the severity of DKA. Method: This study was conducted at Dalhousie University-affiliated hospitals in Nova Scotia, Canada. Ethics approval was obtained. The medical records of 646 emergency visits for 338 patients between November 2015 to December 2018 with a provisional diagnosis of DKA were retrospectively reviewed. 84 records were excluded due to non-anion gap metabolic acidosis, and 66 were excluded due to radiological or microbiological evidence of infection (positive urine, stool or blood cultures, pneumonia, etc.). Only the first set of blood investigations were analyzed to avoid post-treatment changes in blood composition. WBC differential (neutrophils, basophils, eosinophils, immature granulocyte, lymphocytes, metamyelocytes, monocytes, and myelocytes) and severity of DKA based on pH value (mild: 7.25–7.30, moderate: 7.24-7.00, and severe: <7.00) were analyzed. Result: A total of 496 visits for 277 patients were analyzed, with about 1:1.2 male-to-female ratio and median age of 36.5 years (range 18–90 years), with no significant differences in sex or age in relation to the severity of DKA (P-value= 0.68 and 0.16, respectively). Leukocytosis (WBC >11 x10(9)/L) was seen in 65% (n=314). 32% (n=158) had mild DKA, while 56% (n=273) and 1% (n=57) had moderate and severe DKA, respectively. With increased severity of DKA, higher WBC count and hemoglobin levels were observed (P-value= 0.002 and 0.037, respectively). This is not unexpected due to hemoconcentration. However, monocytes, immature granulocytes, and basophils (percentage unit of the total WBC) increased with the severity of DKA (P-value: 0.004, <0.001, and <0.001, respectively). On the other hand, lymphocytes displayed an inverse relationship to DKA severity (P-value: 0.015). In contrast, eosinophils & neutrophils had no significant correlation to the DKA severity (P-value= 0.96, and 0.44, respectively). Conclusion: The WBC differential (namely, monocytes, immature granulocytes, basophils, & lymphocytes) is associated with the severity of DKA. We propose that the WBC differential be further studied as a prognostic indicator in patients with DKA.

Glucagonomas are rare pancreatic neuroendocrine tumors (pNETs), malignant in 80% of cases, thus highlighting the importance of early diagnosis and treatment. Primary manifestations are diabetes, dermatosis, depression, weight loss, and deep vein thrombosis. Unlike other pNETs, glucagonomas are associated with a higher incidence of thromboembolic events, often resulting in death. We present the case of a glucagonoma patient whose primary manifestation was cerebral sinus venous thrombosis (CS-VT). Early diagnosis enabled curative resection. The purpose of this paper is to review the underlying mechanisms associated with increased coagulopathy in glucagonomas.