The paradox between resistance to hypoxia and liability to hypoxic damage in hyperglycemic peripheral nerves. Evidence for glycolysis involvement

Isolated ventral and dorsal rat spinal roots incubated in normal (2.5 mM) or high glucose (25 mM) concentrations or in high concentrations of other hexoses were exposed transiently to hypoxia (30 min) in a solution of low buffering power. Compound nerve action potentials, extracellular direct current potentials, and interstitial pH were continuously recorded before, during, and after hypoxia. Ventral roots incubated in 25 mM D-glucose showed resistance to hypoxia. Dorsal roots, on the other hand, revealed electrophysiological damage by hyperglycemic hypoxia as indicated by a lack of posthypoxic recovery. In both types of spinal roots, interstitial acidification was most pronounced during hyperglycemic hypoxia. The changes in the sensitivity to hypoxia induced by high concentrations of D-glucose were imitated by high concentrations of D-mannose. In contrast, D-galactose, L-glucose, D-fructose, and L-fucose did not have such effects. Resistance to hypoxia, hypoxia-generated interstitial acidification, and hypoxia-induced electrophysiological damage were absent after pharmacological inhibition of nerve glycolysis with iodoacetate. These observations indicate 1) that enhanced anaerobic glycolysis produces resistance to hypoxia in hyperglycemic peripheral nerves and 2) that acidification may impair the function of peripheral axons when anaerobic glycolysis proceeds in a tissue with reduced buffering power

Epidemiology and immunogenetic background of islet cell antibody - positive nondiabetic schoolchildren : Ulm-Frankfurt population study

Islet cell antibodies (ICAs) were determined in a large cohort of white nondiabetic schoolchildren (n = 4287) from a homogenous population in southern Germany. The prevalence of ICA levels greater than or equal to 5 Juvenile Diabetes Foundation (JDF) U was 1.05% (95% confidence interval 0.8-1.4%). Analysis of HLA-DR beta and -DQ beta alleles revealed that the specificities found to be increased in insulin-dependent (type I) diabetic subjects with the same ethnic background were also associated with ICA positivity in the nondiabetic schoolchildren. HLA-DR3 (P less than 0.01) and -DR4 (P less than 0.01) phenotypes and absence of Asp residue (P less than 0.01) at codon 57 of the HLA-DQ beta-chain were significantly increased in ICA+ compared with control subjects. High levels of ICAs, which were categorized as either greater than or equal to 17 or greater than or equal to 30 JDF U, were found to be associated with amino acids other than Asp at position 57 of the HLA-DQ beta-chain. No association of ICA level was found for HLA-DR phenotypes

Cytoplasmic islet cell antibodies recognize distinct islet antigens in IDDM but not in stiff man syndrome

Cytoplasmic islet cell antibodies are well-established predictive markers of IDDM. Although target molecules of ICA have been suggested to be gangliosides, human monoclonal ICA of the immunoglobulin G class (MICA 1-6) produced from a patient with newly diagnosed IDDM recognized glutamate decarboxylase as a target antigen. Here we analyzed the possible heterogeneity of target antigens of ICA by subtracting the GAD-specific ICA staining from total ICA staining of sera. This was achieved 1) by preabsorption of ICA+ sera with recombinant GAD65 and/or GAD67 expressed in a baculovirus system and 2) by ICA analysis of sera on mouse pancreas, as GAD antibodies do not stain mouse islets in the immunofluorescence test. We show that 24 of 25 sera from newly diagnosed patients with IDDM recognize islet antigens besides GAD. In contrast, GAD was the only islet antigen recognized by ICA from 7 sera from patients with stiff man syndrome. Two of these sera, however, recognized antigens besides GAD in Purkinje cells. In patients with IDDM, non-GAD ICA were diverse. One group, found in 64% of the sera, stained human and mouse islets, whereas the other group of non-GAD ICA was human specific. Therefore, mouse islets distinguish two groups of non-GAD ICA and lack additional target epitopes of ICA besides GAD. Longitudinal analysis of 6 sera from nondiabetic ICA+ individuals revealed that mouse-reactive ICA may appear closer to clinical onset of IDDM in some individuals

Employing Visual Analytics to Understand Worldwide Prevalence and Impact of Diabetes Epidemic

The International Diabetes Federation (IDF) has declared diabetes to be one of the largest global health emergencies of the 21st century (International Diabetes Federation). IDF estimates about 415 million adults have diabetes currently and about 318 million adults having impaired glucose tolerance, making them highly susceptible to develop diabetes. As per the estimate in the year 2012, 29.1 million Americans, or 9.3% of the population, had diabetes, and diabetes was the 7th leading cause of death in the United States (American Diabetes Association). Also, the United States has the 3rd largest number of confirmed cases of diabetes after China and India (Albert Einstein College of Medicine). Diabetes is dangerous because it engenders gradual long-term complications like cardiovascular disease, nerve and kidney damage, blindness, hearing loss, and Alzheimer’s disease (Mayoclinic). In this study, we employ visual analytics to analyze and understand the prevalence and impact of diabetes worldwide and within the United States. Our analysis uncovers countries and the counties in the United States that are at higher risk of diabetes, where preventive measures and early detection can help save lives and reduce medical expenses

Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks?

In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice

Assessing the effectiveness of a clinic-based diabetes management program in a community setting

Diabetes in the United States occurs in approximately 8% of adults.[i] Diabetes, if not treated, can lead to many health problems such as blindness or loss of physical functioning, sometimes leading to amputation. However, Type 2 diabetes can be cured or kept under control through effective diabetes management. Many Type 2 diabetes patients let their diabetes become out of control through at risk behaviors, such as smoking, and poor diet, which in turn can lead to a worsening of their condition. With effective disease management, patients can avoid more severe effects of the disease and have higher quality of life. Joslin Diabetes Center operates a diabetes management program called “Why WAIT”. Why Wait is a medically managed clinic-based program to teach Type 2 diabetes patients how to control and manage their diabetes. Joslin Diabetes Center has modified this program and initiated it in a community setting. Here I evaluate whether the community-based program can have similar outcomes to the clinic-based one. The modified community based program was at the Wang YMCA Center and involved seven participants who had full disclosure of the program in a hope to improve their diabetes management. Outcomes measured were Hemoglobin A1c, weight loss, and patient satisfaction collected through participant surveys and program staff. Bringing the Why Wait medically managed clinic-based program into a community setting at the Wang YMCA brings better benefits to the population of Type 2 diabetes patients through increased patient satisfaction. [i] Diabetes.niddk.nih.gov (2011). National Diabetes Statistics, 2011 - National Diabetes Information Clearinghouse. [online] Retrieved from: http://diabetes.niddk.nih.gov/dm/pubs/statistics/index.aspx#fast [Accessed: 21 Mar 2013]

Care, Education, protection – the Associação Protectora dos Diabéticis de Portugal goes from strength to strength

The Portuguese Diabetes Association is the world’s oldest diabetes association and a senior Member Association of the International Diabetes Federation. From the moment it was founded, early in the 20th century, to the present day, the Associação has been driven by a single overarching objective: to improve the quality of life of people with diabetes. Involved nationally in diabetes advocacy and the provision of education, as well as the delivery of care, APDP has become a key player in the healthcare arena in Portugal and its activities reach many thousands of people with diabetes

SGLT2 Inhibitors and the Diabetic Kidney

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether SGLT2 inhibitors, in addition to their glycemic and blood pressure benefits, may provide nephroprotective effects

Developing Comprehensive Diabetes Education Materials for Structured Patient Education Programs in Primary Care Setting

Diabetes education is a key factor for a successful diabetes care. Comprehensive diabetes education materials for conducting structured diabetes education programs were rarely found in primary care setting in Indonesia. There was a need for developing new, comprehensive diabetes education materials for low-literate readers. Developing these education materials followed standard steps in developing print materials, and took account tips for writing low literacy materials for poor readers. The new diabetes education materials consisted of ten various leaflets, also printed as14 posters and 14 x-banners. The ten diabetes leaflets were pre-tested to 5 people with type 2 diabetes (T2D). After minor revisions, the leaflets were printed and distributed to 88 people with T2D attending two structured diabetes education programs in Yogyakarta City. These 88 people were requested to evaluate the leaflets using an evaluation form consisting of four items on language usage, font size, use of pictures, and diabetes information with a 1-10 rating scale; and an open-ended question for improvement. Descriptive statistics were used to analyze the results. Most participants thought that the leaflets were easy to understand and read, interesting, and simple. Majority of participants (79.7%) gave favorable comments without providing suggestions for improvement, such as: “The diabetes leaflets are already good and easy to understand” One third of the participants gave suggestions for improvement. The comprehensive diabetes leaflets developed were well received and highly appreciated by people with T2D attending diabetes education programs