Journal articles: 'Type 2 diabetes; Hyperglycaemia' – Grafiati (2024)

Abstract:

How acute hyperglycaemia affects memory functions and functional brain responses in individuals with and without type 2 diabetes is unclear. Our aim was to study the association between acute hyperglycaemia and working, semantic, and episodic memory in participants with type 2 diabetes compared to a sex- and age-matched control group. We also assessed the effect of hyperglycaemia on working memory–related brain activity. A total of 36 participants with type 2 diabetes and 34 controls (mean age, 66 years) underwent hyperglycaemic clamp or placebo clamp in a blinded and randomised order. Working, episodic, and semantic memory were tested. Overall, the control group had higher working memory (mean z-score 33.15 ± 0.45) than the group with type 2 diabetes (mean z-score 31.8 ± 0.44, p = 0.042) considering both the placebo and hyperglycaemic clamps. Acute hyperglycaemia did not influence episodic, semantic, or working memory performance in either group. Twenty-two of the participants (10 cases, 12 controls, mean age 69 years) were randomly invited to undergo the same clamp procedures to challenge working memory, using 1-, 2-, and 3-back, while monitoring brain activity by blood oxygen level–dependent functional magnetic resonance imaging (fMRI). The participants with type 2 diabetes had reduced working memory during the 1- and 2-back tests. fMRI during placebo clamp revealed increased BOLD signal in the left lateral frontal cortex and the anterior cingulate cortex as a function of working memory load in both groups (3>2>1). During hyperglycaemia, controls showed a similar load-dependent fMRI response, whereas the type 2 diabetes group showed decreased BOLD response from 2- to 3-back. These results suggest that impaired glucose metabolism in the brain affects working memory, possibly by reducing activity in important frontal brain areas in persons with type 2 diabetes.

Abstract:

SummaryEpidemiological studies have shown a strong association between type 2 diabetes mellitus and cardiovascular diseases, and hypofibrinolysis may contribute to this phenomenon. The aim of this study was to determine the effect of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor (TAFI). Hyperglycaemia was mimicked in vitro by incubation of TAFI with glyceraldehyde and in vivo by hyperglycaemic clamping of healthy volunteers. The effects of long-term hyperglycaemia in vivo on TAFI were investigated by comparing TAFI from poorly regulated and tightly regulated patients with type 2 diabetes. In vitro glycated TAFI showed an altered migration pattern on SDS-PAGE due to aggregation. Glycated TAFI showed decreased activity after activation by thrombin-thrombomodulin in a glyceraldehyde-dosedependent manner and a reduced anti-fibrinolytic potential. In vivo, no differences in TAFI parameters were found after hyper-glycaemic clamping of healthy volunteers and between tightly and poorly regulated patients with type 2 diabetes. Moreover, TAFI purified from poorly regulated and tightly regulated patients with type 2 diabetes migrated similarly on SDS-PAGE, indicating little or no glycation of the protein. Despite the deleterious effects of glycation of TAFI in vitro on its function, TAFI was neither affected by hyperglycaemic clamping, nor by long-term hyperglycaemia in patients with type 2 diabetes. This is in contrast to fibrinolytic factors as plasminogen-activator inhibitor I and tissue-type plasminogen activator, which are affected. We therefore hypothesise that a normally functioning TAFI under hyperglycaemic conditions may tip the haemostatic balance towards hypofibrinolysis, which may contribute to the development of cardiovascular diseases in type 2 diabetic patients.

Abstract:

The aim of the present study was to assess the level of glycaemic control by the measurement of 24 h blood glucose profiles and standard blood analyses under identical nutritional and physical activity conditions in patients with Type II diabetes and healthy normoglycaemic controls. A total of 11 male patients with Type II diabetes and 11 healthy matched controls participated in a 24 h CGMS (continuous subcutaneous glucose-monitoring system) assessment trial under strictly standardized dietary and physical activity conditions. In addition, fasting plasma glucose, insulin and HbA1c (glycated haemoglobin) concentrations were measured, and an OGTT (oral glucose tolerance test) was performed to calculate indices of whole-body insulin sensitivity, oral glucose tolerance and/or glycaemic control. In the healthy control group, hyperglycaemia (blood glucose concentration >10 mmol/l) was hardly present (2±1% or 0.4±0.2/24 h). However, in the patients with Type II diabetes, hyperglycaemia was experienced for as much as 55±7% of the time (13±2 h over 24 h) while using the same standardized diet. Breakfast-related hyperglycaemia contributed most (46±7%; P<0.01 as determined by ANOVA) to the total amount of hyperglycaemia and postprandial glycaemic instability. In the diabetes patients, blood HbA1c content correlated well with the duration of hyperglycaemia and the postprandial glucose responses (P<0.05). In conclusion, CGMS determinations show that standard measurements of glycaemic control underestimate the amount of hyperglycaemia prevalent during real-life conditions in Type II diabetes. Given the macro- and micro-vascular damage caused by postprandial hyperglycaemia, CGMS provides an excellent tool to evaluate alternative therapeutic strategies to reduce hyperglycaemic blood glucose excursions.

Abstract:

Diabetes is a common risk factor for cardiovascular disease. Coronary heart disease and left ventricular dysfunction are more common in diabetic patients than in non-diabetic patients, and diabetic patients benefit less from revascularisation procedures. This increased risk can only partly be explained by the adverse effects of diabetes on established risk factors; hence, a substantial part of the excess risk must be attributable to direct effects of hyperglycaemia and diabetes. In type 2 diabetes, hyperinsulinaemia, insulin resistance and hyperglycaemia have a number of potential adverse effects, including effects on endothelial function and coagulation. Risk factor modification has been shown to reduce the occurrence of cardiovascular events in patients with diabetes; indeed, diabetic patients appear to benefit more in absolute terms than non-diabetic patients. There is thus a strong case for intensive treatment of risk factors, including insulin resistance and hyperglycaemia, in patients with type 2 diabetes.

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Abstract Diabetes mellitus is chronic disorder characterized by hyperglycaemia. Hyperglycaemia induces mitochondrial dysfunction, enhances oxidative stress and thus promotes reactive oxygen species (ROS) production. Earlier studies suggested that reactive oxygen species (ROS) are involved in the pathogenesis of many diseases. Previous studies have revealed that hyperglycaemia changes the functional phenotype of monocytes, macrophages, neutrophils, NK cells and CD8+ T cells. The aim of this study was to investigate whether diabetes affects the functional phenotype of NKT cells. Diabetes mellitus was induced in BALB/c mice by intraperitoneal injection of streptozotocin at a single dose of 170 mg/kg body weight. The number and functional phenotype of splenic NKT cells was assessed by fl ow cytometry, 28 days after diabetes induction. The diabetic condition facilitated the production of antioxidant enzymes, including catalase (p<0.05) and superoxide dismutase. Hyperglycaemia enhanced oxidative stress and thus decreased the number of splenic NKT cells but did not change the percentage of splenic CD3+CD49+ NKT cells that express the activatory receptor NKP46 or produce IFN-γ. However, hyperglycaemia increased the frequency of splenic NKT cells that express KLRG-1 and produce TGF-β, IL-4, and IL-5, and it decreased the frequency of IL-17+ NKT cells. Our study indicates that diabetes mellitus induces oxidative stress and switches the functional phenotype of NKT cells towards type 2 (IL-4 and IL-5 producing NKTs) and regulatory (TGF-β Thproducing NKTs) phenotypes. These findings are correlated with the clinical observation in humans that diabetic patients are more prone to infections and tumours.

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The number of elderly persons with diabetes mellitus type 2 is expected to progressively increase. Management of this category of patients should be individualised and include the adequate correction of hyperglycaemia, prevention of long-term complications, prevention of hypoglycaemia, reduction of cardiovascular mortality and preservation of quality of life. This article summarises basic information on the pathophysiology of carbohydrate metabolism, peculiarities of the course of diabetes and use of antidiabetic drugs in the elderly. Special attention is paid to reviewing the goals of glycaemic control and proposed clinical guidelines.

Abstract:

ObjectivesWith the increasing burden of non-communicable diseases in low-income and middle-income countries, biological risk factors, such as hyperglycaemia, are a major public health concern in Bangladesh. Hyperglycaemia is an excess of glucose in the bloodstream and is often associated with type 2 diabetes mellitus. Nationally representative data of hyperglycaemia prevalence starting from age ≥18 years are currently unavailable for Bangladeshi adults. The objective of this study was to assess the prevalence and determinants of hyperglycaemia among adults in Bangladesh aged ≥18 years.Study designCross-sectional, population-based study.Setting and participantsData for this analysis were collected in November to December 2015, from a population-based nationally representative sample of 1843 adults, aged ≥18 years, from both urban and rural areas of Bangladesh. Demographic information, capillary blood glucose, blood pressure, height, weight, waist circumference and treatment history were recorded.Primary outcome measuresHyperglycaemia was defined as a random capillary blood glucose level of ≥11.1 mmol/L (ie, in the diabetic range) or currently taking medication to control type 2 diabetes, based on self-report.ResultsOverall, the prevalence of hyperglycaemia was 5.5% (95% CI 4.5% to 6.6%) and was significantly higher among urban (9.8%, 95% CI 7.7% to 12.2%) than rural residents (2.8%, 95% CI 1.9% to 3.9%). The age-standardised prevalence of hyperglycaemia was 5.6% (95% CI 4.6% to 6.8%). Among both urban and rural residents, the associated determinants of hyperglycaemia included hypertension and abdominal obesity. About 5% of the total population self-reported have been previously diagnosed with type 2 diabetes; among these adults, over 25% were not taking medications to control their diabetes.ConclusionsOur study found that about 1 in 20 Bangladeshi adults aged ≥18 years have hyperglycaemia. To control and prevent the development of type 2 diabetes, data from this study can be used to inform public health programming and provide descriptive information on surveillance of progress towards controlling diabetes in Bangladesh.

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Little is known regarding the role of hyperglycaemia on histone H3 modifications and, in turn, altering the expression of genes during the development of diabetes-associated complications. In the present study, we have investigated the hyperinsulinaemia/hyperglycaemia-induced epigenetic changes and alteration of Fbn1 (fibrillin 1) and Col3A1 (collagen type III α1) gene expression. Insulin resistance and Type 2 diabetes in male Sprague–Dawley rats was developed by feeding rats an HFD (high-fat diet) and administering a low dose of STZ (streptozotocin). Hyperglycaemia induced deacetylation and dephosphorylation of histone H3 in the heart and kidneys of diabetic rats. Furthermore, mRNA expression of Fbn1 and Col3A1 increased in the kidneys and decreased in the heart under hyperglycaemic/hyperinsulinaemic conditions. Similar to mRNA expression, chromatin immunoprecipitation also showed an increase in the level of histone H3 acetylation of the Fbn1 gene, but not of the Col3A1 gene. Our present findings suggests that the change in expression of the Fbn1 gene is epigenetically regulated, but the expression of the Col3A1 gene may either be independent of epigenetic regulation or may involve other histone modifications. We provide the first evidence regarding the role of hyperglycaemia/hyperinsulinaemia in altering histone H3 modifications, which may result in the alteration of extracellular matrix gene expression.

Abstract:

Patients with type 2 diabetes mellitus have an increased risk of cardiovascular (CV) complications. Although hyperglycaemia contributes to the pathogenesis of atherosclerosis and heart failure in these patients, glucose-lowering strategies did not have a significant effect on reducing CV risk, particularly in patients with a long duration of type 2 diabetes mellitus and prevalent CV disease (CVD). Sodium-glucose linked transporter-2 (SGLT2) inhibitors are a new class of anti-hyperglycaemic medications that increase glycaemic control via insulin-dependent mechanism of action associated with increased urinary glucose excretion.In this review, we present an analysis of the Empa-Reg Outcomes investigation, focussed on assessing the CV safety of empagliflozin, an inhibitor of SGLT2. We discuss the impressive results of trials that provide evidence on the cardiac and renal properties of empagliflozin. We present and analyse the current hypothesis on the mechanism of action of glucose-lowering medication, which has such a severe and complex impact on outcomes in patients with type 2 diabetes at high CV risk.

Abstract:

SummaryMegakaryocyte (MK)-derived miRNAs have been detected in platelets. Here, we analysed the expression of platelet and circulating miR-223, miR-26b, miR-126 and miR-140 that might be altered with their target mRNAs in type 2 diabetes mellitus (DM2). MiRNAs were isolated from leukocyte-depleted platelets and plasma samples obtained from 28 obese DM2, 19 non-DM obese and 23 healthy individuals. The effect of hyperglycaemia on miRNAs was also evaluated in MKs using MEG-01 and K562 cells under hyperglycaemic conditions after 8 hours up to four weeks. Quantitation of mature miRNA, pre-miRNAs and target mRNA levels (P2RY12 and SELP) were measured by RT-qPCR. To prove the association of miR-26b and miR-140 with SELP (P-selectin) mRNA level, overexpression or inhibition of these miRNAs in MEG-01 MKs was performed using mimics or anti-miRNAs, respectively. The contribution of calpain substrate Dicer to modulation of miRNAs was studied by calpain inhibition. Platelet activation was evaluated via surface P-selectin by flow cytometry. Mature and pre-forms of investigated miRNAs were significantly reduced in DM2, and platelet P2RY12 and SELP mRNA levels were elevated by two-fold at increased platelet activation compared to controls. Significantly blunted miRNA expressions were observed by hyperglycaemia in MEG-01 and K562-MK cells versus baseline values, while the manipulation of miR-26b and miR-140 expression affected SELP mRNA level. Calpeptin pretreatment restored miRNA levels in hyperglycaemic MKs. Overall, miR-223, miR-26b, miR-126 and miR-140 are expressed at a lower level in platelets and MKs in DM2 causing upregulation of P2RY12 and SELP mRNAs that may contribute to adverse platelet function.Supplementary Material to this article is available online at www.thrombosis-online.com.

Abstract:

Background: Type 2 diabetes mellitus (T2DM) has emerged as a pandemic. It has different complications, both microvascular and macrovascular. Objective: The purpose of this review is to summarize the different types of macrovascular complications associated with T2DM. Methods: A comprehensive review of the literature was performed to identify clinical studies, which determine the macrovascular complications associated with T2DM. Results: Macrovascular complications of T2DM include coronary heart disease, cardiomyopathy, arrhythmias and sudden death, cerebrovascular disease and peripheral artery disease. Cardiovascular disease is the primary cause of death in diabetic patients. Many clinical studies have shown a connection between T2DM and vascular disease, but almost always other risk factors are present in diabetic patients, such as hypertension, obesity and dyslipidaemia. Conclusion: T2DM causes a variety of macrovascular complications through different pathogenetic pathways that include hyperglycaemia and insulin resistance. The association between T2DM and cardiovascular disease is clear, but we need more clinical studies in order to identify the pure effect of T2DM.

Abstract:

Aim: Recent data have suggested that effective control of postprandial blood glucose can reduce the risk of macroangiopathic complications of diabetes, especially cardiovascular risk. 1,5-Anhydro-D-glucitol (1,5-AG) has been proposed as a marker of short-term hyperglycaemic excursions. We aimed to evaluate its usefulness in patients with type 2 diabetes and have attempted to indicate when 1,5-AG monitoring should be used in ordinary diabetes care settings. Methods: The study group consisted of 130 type 2 diabetic patients aged 36–69 years. 1,5-AG plasma level, HbA1c concentrations and daily glucose profile were measured. Mean blood glucose (MBG), M-value were calculated and maximal daily glycaemia (MxG) was established as indicators of short-term hyperglycaemic episodes. Results: 1,5-AG plasma level was negatively and HbA1c was positively correlated with fasting glycaemia (FG), MBG, M-value and MxG. Multivariate regression analysis revealed that 1,5-AG plasma level is determined by MxG only, while FG determined HbA1c concentration in blood. The analysis of 1,5-AG level and HbA1c distributions in well and poorly controlled patients revealed that persons with low HbA1c values may have decreased 1,5-AG plasma level. Conclusion: 1,5-AG plasma level monitoring is the useful method to identify well controlled, exclusively based on HbA1c levels type 2 diabetic patients with transient hyperglycaemia, accordingly patients at high risk of macroangiopathic complications.

Abstract:

The incidence of type 2 diabetes is rapidly rising worldwide leading to an increasing burden of cardiovascular and microvascular complications. The aim of treatment of the condition is to improve quality of life and reduce such complications. To this end, improvement in glucose control remains an important consideration. In recent years, important therapeutic advances have occurred in the management of hyperglycaemia in people with type 2 diabetes. These include the use of dipeptidylpeptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium glucose transporter-2 inhibitors. The latter two classes appear to have some specific beneficial effects on cardiovascular and renal outcomes, independent of their antihyperglycaemic effects. This review aims to outline the current state of diagnosis and management of diabetes for the general physician, with a particular focus on new therapeutic agents for management of glucose in patients with type 2 diabetes.

Abstract:

Twenty-five years ago, the discovery of endothelium-derived relaxing factor opened a door that revealed a new and exciting role for the endothelium in the regulation of blood flow and led to the discovery that nitric oxide (NO) multi-tasked as a novel cell-signalling molecule. During the next 25 years, our understanding of both the importance of the endothelium as well as NO has greatly expanded. No longer simply a barrier between the blood and vascular smooth muscle, the endothelium is now recognized as a complex tissue with heterogeneous properties. The endothelium is the source of not only NO but also numerous vasoactive molecules and signalling pathways, some of which are still not fully characterized such as the putative endothelium-derived relaxing factor. Dysfunction of the endothelium is a key risk factor for the development of macro- and microvascular disease and, by coincidence, the discovery that NO was generated in the endothelium corresponds approximately in time with the increased incidence of type 2 diabetes. Primarily linked to dietary and lifestyle changes, we are now facing a global pandemic of type 2 diabetes. Characterized by insulin resistance and hyperglycaemia, type 2 diabetes is increasingly being diagnosed in adolescents as well as children. Is there a link between dietary-related hyperglycaemic insults to the endothelium, blood flow changes, and the development of insulin resistance? This review explores the evidence for and against this hypothesis.Key words: diabetes, endothelium, hyperglycaemia, insulin, nitric oxide, oxidative stress.

Abstract:

Abstract Context: The Australian Institute of Health and Welfare (AIHW) health survey in 2018 demonstrated that mortality rates from diabetes in remote and very remote areas were twice as high compared to those in the urban regions. Moreover, diabetic patients in the lowest socioeconomic areas were more than twice as likely to die from the disease and its associated complications than those living in the highest socioeconomic areas (77 and 33 per 10,000 respectively) [1]. These health disparities prompted a closer look into the quality of local inpatient diabetes management in order to identify the changes required to improve diabetes care in a rural community. Methods: A retrospective audit assessing all adult patients (aged over 18) with diabetes between August and October 2019 who attended treatment in one rural health centre in Queensland, Australia was conducted. Information was obtained from paper based patient records, especially the state-wide insulin subcutaneous order and blood glucose chart. Results: There were 122 diabetic inpatients during the study period. 9 were excluded due to poor documentation on the details of diabetes or insulin management. Men comprised 62% (n = 75) of the patients and the chronicity of diabetes in the majority of the patients was either unknown or undocumented (n = 90). Type 2 diabetes represented 87% (n = 106) of the hospitalisations. There were 64 hospitalisations with diabetes or diabetic related complications as the principal diagnoses. Among these, 7% (n = 8) were due to diabetic ketoacidosis (DKA), hyperosmolar hyperglycaemic state (HHS) or severe hyperglycaemia with ketosis, while 2 patients (1.7%) presented with hypoglycaemia. The majority (32%, n = 36) of the diabetic related complications were due to an underlying infection. Throughout inpatient stay, half (50.4%, n = 57) of the patients experienced one or more hyperglycaemic episodes and 14% (n = 16) experienced at least one hypoglycaemic events. The prevalence of inappropriate management of hyperglycaemia during this period was observed to be 21%. This was due to prescription errors i.e. usual insulin not prescribed (n = 7), erroneous insulin type (n = 3) and unsigned order (n = 4). Persistent hyperglycaemia, defined locally by blood glucose level (BGL) &gt; 12 mmol/L was not managed ideally in 10 patients due to either lack of communication between staffs and physicians or failure to make changes when notifications were relayed. Patients were followed up until the discharge phase. Nearly half (41.8%, n = 51) of the patients were found to have no clearly documented follow up plans albeit the limitations of paper based clinical records should be taken into account. Conclusion: The management of diabetes in the rural communities can be challenging. Communication between the different layers of healthcare providers is imperative to ensure hyperglycaemia among hospitalised patients is not mismanaged. Clear documentation of insulin doses and BGL levels on paper records as well as regular education and shared clinical experience on insulin titration in response to abnormal BGL levels by clinicians are strategies to improve diabetes care. Reference: 1. Australian Institute of Health and Welfare. 2021. Diabetes, Type 2 Diabetes - Australian Institute Of Health And Welfare. [online] Available at: &lt;https://www.aihw.gov.au/reports/diabetes/diabetes/contents/hospital-care-for-diabetes/type-2-diabetes&gt; [Accessed 6 January 2021].

Abstract:

Depression is twice as common in type 2 diabetes as in the general population and is associated with adverse health outcomes. Growing evidence suggest that type 2 diabetes and depression share biological mechanisms. This brief commentary discusses current understanding of shared biological pathways, focussing on hyperglycaemia, (micro)vascular dysfunction, and low-grade inflammation. Although there is accumulating evidence that these pathways are involved in the link between type 2 diabetes and depression, direct evidence of their temporal associations is lacking because of a paucity of longitudinal studies that focus on the pathobiology of both type 2 diabetes and depression.

Abstract:

This is a case report of a 55-year-old man with Type 2 Diabetes Mellitus who presented with progressive breathlessness, chest pain and hyperglycaemia. An initial impression of a chest infection was made. Management was initiated with antibiotics, but this was unsuccessful, and he continued to desaturate. A screen for Coronavirus Disease of 2019 (COVID-19) returned positive. There was no prodrome of fever or flu-like illness or known contact with a patient known to have COVID-19. This case is instructive as he didn’t fit the typical case definition for suspected COVID-19. There is significant community spread in Ghana, therefore COVID-19 should be a differential diagnosis in patients who present with hyperglycaemia and respiratory symptoms in the absence of a febrile illness. Primary care doctors must have a high index of suspicion in cases of significant hyperglycaemia and inability to maintain oxygen saturation.Patients known to have diabetes and those not known to have diabetes may develop hyperglycaemia subsequent to COVID-19. A high index of suspicion is crucial for early identification, notification for testing, isolation, treatment, contact tracing and possible referral or coordination of care with other specialists. Early identification will protect healthcare workers and patients alike from cross-infection.

Abstract:

Spironolactone prevents vascular remodelling in diabetes by reducing oxidative stress, hypertrophy and cell proliferation in the vascular wall. Thus, MR (mineralocorticoid receptor) antagonism is effective in the prevention of hyperglycaemia-associated vascular injury, reducing organ damage and increasing survival of diabetic patients.

Abstract:

Incretin hormones are important for normal pancreatic islet function and glucose homeostasis. Sensitivity to glucose of the α- and β-cells of the pancreas is diminished in type 2 diabetes mellitus (T2DM), leading to impaired insulin secretion, insulin resistance due to elevated glucagon levels in hyperglycaemia and impaired glucagon counterregulation in hypoglycaemia. In addition, T2DM is associated with increased lipotoxicity-induced insulin resistance. This article is a comprehensive review of the safety and efficacy of vildagliptin in patients with T2DM and evaluates the extra-pancreatic effects of incretin-based therapies. Clinical evidence has proven that vildagliptin effectively decreases HbA1c with a low risk of hypoglycaemia and is weight neutral. Vildagliptin also suppresses postprandial triglyceride (TG)-rich lipoprotein levels after ingestion of fat-rich meals and reduces fasting lipolysis, suggesting inhibition of fat absorption and reduced TG stores in non-fat tissues.

Abstract:

Type 2 diabetes mellitus is the result of interaction between genetic and environmental factors, leading to heterogeneous and progressive pancreaticβ-cell dysfunction. Overweight and obesity are major contributors to the development of insulin resistance and impaired glucose tolerance. The inability ofβcells to secrete enough insulin produces type 2 diabetes. Abnormalities in other hormones such as reduced secretion of the incretin glucagon-like peptide 1 (GLP-1), hyperglucagonemia, and raised concentrations of other counterregulatory hormones also contribute to insulin resistance, reduced insulin secretion, and hyperglycaemia in type 2 diabetes. Clinical-overt and experimental cortisol excess is associated with profound metabolic disturbances of intermediate metabolism resulting in abdominal obesity, insulin resistance, and low HDL-cholesterol levels, which can lead to diabetes. It was therefore suggested that subtle abnormalities in cortisol secretion and action are one of the missing links between insulin resistance and other features of the metabolic syndrome. The aim of this paper is to address the role of glucocorticoids on glucose homeostasis and to explain the relationship between hypercortisolism and type 2 diabetes.

Abstract:

Vascular complications are major causes of morbidity and mortality in type 2 diabetes patients. Mitochondrial reactive oxygen species (ROS) generation and a lack of efficient antioxidant machinery, a result of hyperglycaemia, mainly contribute to this problem. Although advances in therapy have significantly reduced both morbidity and mortality in diabetic individuals, diabetes-associated vascular complications are still one of the most challenging health problems worldwide. New healing options are urgently needed as current therapeutics are failing to improve long-term outcomes. Particular effort has recently been devoted to understanding the functional relationship between chromatin structure regulation and the persistent change in gene expression which is driven by hyperglycaemia and which accounts for long-lasting diabetic complications. A detailed investigation into epigenetic chromatin modifications in type 2 diabetes is underway. This will be particularly useful in the design of mechanism-based therapeutics which interfere with long-lasting activating epigenetics and improve patient outcomes. We herein provide an overview of the most relevant mechanisms that account for hyperglycaemia-induced changes in chromatin structure; the most relevant mechanism is called “metabolic memory.”

Abstract:

Previous studies have postulated the association between oxidative stress and Type 2 diabetes. Considering the long pre-diabetic period with IGR (impaired glucose regulation) and its high risk of developing diabetes, to test this hypothesis, we have investigated oxidative stress pathways and DNA damage in patients with IGR and newly diagnosed Type 2 diabetes. The study population consisted of 92 subjects with NGT (normal glucose tolerance), 78 patients with IGR and 113 patients with newly diagnosed diabetes. Plasma MDA (malondialdehyde) and TAC (total antioxidative capacity) status, erythrocyte GSH content and SOD (superoxide dismutase) activity were determined. A comet assay was employed to evaluate DNA damage. Compared with subjects with NGT, patients with IGR had reduced erythrocyte SOD activity. Patients with diabetes had a higher plasma MDA concentration, but a lower plasma TAC level and erythrocyte SOD activity, than the NGT group. Correlation analysis revealed a strong positive association between IR (insulin resistance) and MDA concentration, but negative correlations with TAC status and SOD activity. With respect to β-cell function, a positive association with TAC status and an inverse correlation with GSH respectively, were observed. The comet assay revealed slight DNA damage in patients with IGR, which was increased in patients with diabetes. Significant correlations were observed between DNA damage and hyperglycaemia, IR and β-cell dysfunction. In conclusion, the results of the present study suggest that hyperglycaemia in an IGR state caused the predominance of oxidative stress over antioxidative defence systems, leading to oxidative DNA damage, which possibly contributed to pancreatic β-cell dysfunction, IR and more pronounced hyperglycaemia. This vicious circle finally induced the deterioration to diabetes.

Abstract:

Background. Despite the fact that there is an increasingly effective armoury of medications to treat diabetes, many people continue to have substantially elevated blood glucose levels. The purpose of this study was to explore what the barriers to diabetes management are in a cohort of people with diabetes and poor glycaemic control. Methods. Qualitative semistructured interviews were carried out with 10 people with diabetes who had known diabetes and a recent HbA1c of >11.3% (100 mmol/mol) to explore their experiences of barriers to diabetes self-management and glycaemic control. Results. Barriers to diabetes management were based around two key themes: biopsychosocial factors and knowledge about diabetes. Specifically, financial concerns, social stigma, medication side effects, and cognitive impairment due to hyperglycaemia were commonly reported as barriers to medication use. Other barriers included a lack of knowledge about their own condition, poor relationships with healthcare professionals, and a lack of relevant resources to support diet and weight loss. Conclusion. People with diabetes with poor glycaemic control experience many of the same barriers as those reported elsewhere, but also experience issues specifically related to their severe hyperglycaemia. Management of diabetes could be improved via the increased use of patient education and availability of locally relevant resources.

Abstract:

Aims. We compared the demographic profile and clinical characteristics of individuals with new onset steroid-induced diabetes (NOSID) to Type 2 diabetes (T2DM) patients with and without steroid treatment. Methods. The demographic profile and clinical characteristics of 60 individuals who developed NOSID were examined and matched to 60 type 2 diabetes patients receiving steroid therapy (T2DM+S) and 360 diabetic patients not on steroids (T2DM) for age, duration of diabetes, HbA1c, gender, and ethnicity. Results. Patients who developed NOSID had less family history of diabetes (P≤0.05) and were less overweight (P≤0.02). NOSID was more commonly treated with insulin. Despite a matching duration of diabetes and glycaemic control, significantly less retinopathy was found in the group of patients with NOSID (P<0.03). Conclusions. It appears that steroid treatment primarily precipitated diabetes in a group of individuals otherwise less affected by risk factors of diabetes at that point in time, rather than just opportunistically unmasking preexisting diabetes. Furthermore, the absence of retinopathy suggests that patients with NOSID had not been exposed to long periods of hyperglycaemia. However, the impact of the underlying conditions necessitating steroid treatment and concomitant medications such as immunosuppressants on diabetes development remain to be defined.

Abstract:

This case study aims to discuss the unusual forms of hyperthyroidism presentation, the nonspecific symptoms and precipitating events. A 70-year-old male was taken to the emergency department for hyperglycaemia, nausea, vomiting and altered mental status with a week of evolution. He had a past medical history of type 2 diabetes, hypertension and dyslipidemia. He had no history of any recent intercurrent illness or infection. At the emergency room, besides hyperglycaemia, ketonemia and slightly elevated C-reactive protein, the basic laboratory panel workup was normal, as was the head computed tomography. He was admitted for metabolic compensation and to study the altered neurological status. During hospitalisation, despite the good glycemic control, he had no improvements in neurological status. At day four of hospitalisation, thyrotoxicosis with thyroid storm criteria was diagnosed. He started on adequate treatment with complete clinical recovery. The associated morbidity and mortality of thyroid storm requires immediate recognition and treatment. Elderly patients are frequently misdiagnosed or diagnosed later due to fewer and less pronounced signs and symptoms.

Abstract:

Background: Type 2 diabetes mellitus (T2DM) is a chronic, non communicable, multisystem disease that has reached epidemic proportions. Chronic exposure to hyperglycaemia affects the microvasculature, eventually leading to diabetic nephropathy, retinopathy and neuropathy with high impact on the quality of life and overall life expectancy. Sexual dysfunction is an often-overlooked microvascular complication of T2DM, with a complex pathogenesis originating from endothelial dysfunction. Objective: The purpose of this review is to present current definitions, epidemiological data and risk factors for diabetic retinopathy, nephropathy, neuropathy and sexual dysfunction. We also describe the clinical and laboratory evaluation that is mandatory for the diagnosis of these conditions. Method: A comprehensive review of the literature was performed to identify data from clinical studies for the prevalence, risk factors and diagnostic methods of microvascular complications of T2DM. Results: Diabetic nephropathy and retinopathy affect approximately 25% of patients with T2DM; diabetic neuropathy is encountered in almost 50% of the diabetic population, while the prevalence of erectile dysfunction ranges from 35-90% in diabetic men. The duration of T2DM along with glycemic, blood pressure and lipid control are common risk factors for the development of these complications. Criteria for the diagnosis of these conditions are well established, but exclusion of other causes is mandatory. Conclusion: Early detection of microvascular complications associated with T2DM is important, as early intervention leads to better outcomes. However, this requires awareness of their definition, prevalence and diagnostic modalities.

Abstract:

The prevalence of type 2 diabetes mellitus is expected to rise in the frail elderly population, which will have significant consequences for the health economy. Symptoms of hypoglycaemia can be subtle in the elderly. Hypoglycaemia accounts for more hospital admissions than hyperglycaemia. Treatment targets are set based on the risk of adverse events resulting from treatment and the benefits expected from tighter glycaemic control. The different medications available are discussed including the different types of insulin, in particular relation to usage in older adults. The choice of therapy is based on the targets, comorbidities and the characteristics of each antidiabetic agent. Deintensification of therapy should be considered in patients who experience adverse effects. Treatment guidelines should be formulated based on the above principles, as many current guidelines do not incorporate deintensification of therapy.

Abstract:

Pancreatic bi-hormones insulin and glucagon are the Yin and Yang in the regulation of glucose metabolism and hom*oeostasis. Insulin is synthesized primarily by pancreatic β-cells and is released in response to an increase in blood glucose levels (hyperglycaemia). By contrast, glucagon is synthesized by pancreatic α-cells and is released in response to a decrease in blood glucose (hypoglycaemia). The principal role of glucagon is to counter the actions of insulin on blood glucose hom*oeostasis, but it also has diverse non-hyperglycaemic actions. Although Type 1 diabetes is caused by insulin deficiency (insulin-dependent) and can be corrected by insulin replacement, Type 2 diabetes is a multifactorial disease and its treatment is not dependent on insulin therapy alone. Type 2 diabetes in humans is characterized by increased insulin resistance, increased fasting blood glucose, impaired glucose tolerance and the development of glomerular hyperfiltration and microalbuminuria, ultimately leading to diabetic nephropathy and end-stage renal disease. Clinical studies have suggested that an inappropriate increase in hyperglycaemic glucagon (hyperglucagonaemia) over hypoglycaemic insulin (not insulin deficiency until advanced stages) plays an important role in the pathogenesis of Type 2 diabetes. However, for decades, research efforts and resources have been devoted overwhelmingly to studying the role of insulin and insulin-replacement therapy. By contrast, the implication of glucagon and its receptor signalling in the development of Type 2 diabetic metabolic syndromes and end-organ injury has received little attention. The aim of this review is to examine the evidence as to whether glucagon and its receptor signalling play any role(s) in the pathogenesis of Type 2 diabetic renal injury, and to explore whether targeting glucagon receptor signalling remains only a theoretical antidiabetic strategy in Type 2 diabetes or may realize its promise in the future.

Abstract:

Type 2 diabetes is a pandemic disease with an incidence that has risen steadily over recent decades. Experimental evidence in animals has demonstrated that intestinal bypass surgery of the upper small intestine, particularly the duodenum, has an important role in glucose hom*oeostasis. Furthermore, Roux-en-Y bypass performed as bariatric surgery has shown to correct hyperglycaemia from the first postoperative days in obese diabetic patients. Therefore, on the basis of these considerations, duodenal mucosal resurfacing was studied in type 2 diabetes patients as a minimally invasive procedure that could offer an alternative treatment for these patients. Further studies, and particularly large controlled trials, are needed to determine the place of this procedure in the treatment of type 2 diabetes as well as other metabolic diseases such as non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.

Abstract:

The majority of people with diabetes have type 2 diabetes (T2D), where hyperglycaemia occurs because the islet β-cells are unable to secrete enough insulin, usually in the context of insulin resistance that arises because of fat mass expansion. There are a range of pharmacotherapies in current use to treat T2D and pharmaceutical companies are actively engaged in the development of novel therapies for better glucose control. Ligands that target G-protein-coupled receptors (GPCRs) are obvious candidates because they are used successfully for a wide range of disorders and GLP-1 receptor agonists, which are a relatively recent class of diabetes therapy, have proved to be very effective in treating T2D. We provide here an overview of current successes, some drawbacks and future possibilities for GPCR-based T2D therapies.

Abstract:

Background: Diabetes is a group of disorders characterized by high blood glucose levels. Disturbances in serum electrolytes sodium (Na+), potassium (K+) and chloride (Cl‑) is found in diabetes. The objective of the study was to investigate the disturbances in concentrations of serum electrolytes in hyperglycaemic crisis, uncontrolled non – insulin dependent diabetes mellitus patients: early detection and treatment of such abnormalities, leading to better quality of life of patients.Methods: Data was collected prospectively over a period of 1 year and analyzed retrospectively. Of the 131 subjects included in the study, two groups were formed; 60 hyperglycaemic diabetes mellitus patients and 71 healthy volunteer as controls. Biochemical analysis for Na+, K+, Cl- was performed by ISE method using Easy – lyte automatic electrolyte analyzer. The random glucose levels were estimated by direct Hexokinase enzymatic method using Cobas Interga 400. Unpaired t-test was done to find out the difference between the two paired groups and Pearson's correlation was calculated to know the correlations between electrolytes and random glucose levels.Results: In uncontrolled diabetes mellitus, increase in serum Na+ and Cl- levels were observed to be highly significant (p<0.001, respectively) while that of K+ showed significant (p<0.05) alterationsConclusions: The study demonstrated significant association of Na+, K+ and Cl- with hyperglycaemia in patients with hyperglycaemic crisis in uncontrolled type 2 diabetes mellitus. So, electrolytes should be measured during the treatment of type 2 diabetes mellitus.