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Sample records for advanced age diabetes

  1. Advanced glycation end products (AGEs) and diabetic vascular complications.

    PubMed

    Yamagishi, Sho-ichi; Nakamura, Kazuo; Imaizumi, Tsutomu

    2005-02-01

    Diabetic vascular complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Chronic hyperglycemia is essentially involved in the development and progression of diabetic micro- and macroangiopathy. Among various metabolic derangements implicated in the pathogenesis of diabetic vascular complication, advanced glycation end product (AGE) hypothesis is most compatible with the theory of 'hyperglycemic memory'. In this review, we discuss the molecular mechanisms of diabetic vascular complication, specially focusing on AGEs and their receptor (RAGE) system. Several types of AGE inhibitors and their therapeutic implications in this devastating disorder are also discussed here. PMID:18220586

  2. Advanced glycation end products (AGEs) and their receptor (RAGE) system in diabetic retinopathy.

    PubMed

    Yamagishi, Sho-ichi; Nakamura, Kazuo; Matsui, Takanori

    2006-03-01

    Vascular complications are a leading cause of blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. There is a growing body of evidence that formation and accumulation of advanced glycation end products (AGEs) progress during normal aging, and at an extremely accelerated rate in diabetes, thus being involved in the pathogenesis of diabetic vascular complications. Furthermore, the interaction by AGEs of their receptor, RAGE, activates down-stream signaling and evokes inflammatory responses in vascular wall cells. Therefore, inhibition of AGE formation or blockade of the RAGE signaling may be a promising target for therapeutic intervention to prevent diabetic vascular complications. This review discusses the molecular mechanisms of diabetic retinopathy, especially focusing on the AGE-RAGE system. Several types of inhibitors of the AGE-RAGE system and their therapeutic implications are also reviewed here. PMID:16712466

  3. Role of advanced glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of diabetic microangiopathy.

    PubMed

    Yamagishi, S; Takeuchi, M; Inagaki, Y; Nakamura, K; Imaizumi, T

    2003-01-01

    Diabetic vascular complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Chronic hyperglycemia is essentially involved in the pathogenesis of diabetic micro- and macrovascular complications via various metabolic derangements. In this review, we discuss the molecular mechanisms of diabetic retinopathy and nephropathy, especially focusing on advanced glycation end products (AGEs) and their receptor (RAGE) system. Several types of AGE inhibitors and their therapeutic implications in diseases, including diabetic microangiopathy, will be discussed in the next review article. PMID:15224502

  4. Advanced BrainAGE in older adults with type 2 diabetes mellitus.

    PubMed

    Franke, Katja; Gaser, Christian; Manor, Brad; Novak, Vera

    2013-01-01

    Aging alters brain structure and function and diabetes mellitus (DM) may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors, and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain magnetic resonance images (MRI). The "Brain Age Gap Estimation" (BrainAGE) score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM) completed an MRI at 3Tesla, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM) also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001), whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034), whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor alpha (TNFα) levels, lower verbal fluency scores and more severe deprepession. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019) and increased fasting blood glucose levels (r = 0.34, p = 0.025). In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2 DM

  5. Chronic Ingestion of Advanced Glycation End Products Induces Degenerative Spinal Changes and Hypertrophy in Aging Pre-Diabetic Mice

    PubMed Central

    Illien-Jünger, Svenja; Lu, Young; Qureshi, Sheeraz A.; Hecht, Andrew C.; Cai, Weijing; Vlassara, Helen; Striker, Gary E.; Iatridis, James C.

    2015-01-01

    Intervertebral disc (IVD) degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs), cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG)) on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+) or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG). dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions. PMID:25668621

  6. Lysozyme enhances renal excretion of advanced glycation endproducts in vivo and suppresses adverse age-mediated cellular effects in vitro: a potential AGE sequestration therapy for diabetic nephropathy?

    PubMed Central

    Zheng, F.; Cai, W.; Mitsuhashi, T.; Vlassara, H.

    2001-01-01

    BACKGROUND: Lysozyme (LZ), a host-defense protein, contains an 18 amino-acid domain with high affinity binding for sugar-derived proteins or lipids, called advanced glycation endproducts (AGE), that are implicated in diabetes- and age-dependent complications (DC). MATERIALS AND METHODS: A) The effects of LZ on AGE- removal were tested in vivo. LZ was injected (200 ug/day, i.p., X2 weeks) in non-obese diabetic (NOD), db/db (+/+) mice, and non-diabetic, AGE-infused Sprague-Dawley rats. B) LZ: AGE interactions with macrophage-like T1B-183 cells (Mf) and mesangial cells (MC) were tested in vitro. RESULTS: A) In NOD mice, LZ reduced the elevated basal serum AGE (sAGE) (p < 0.05), enhanced urinary AGE (uAGE) excretion by approximately 2-fold (p < 0.01), while it reduced albuminuria (UA), p < 0.005. In db/db mice, LZ infusion also reduced the elevated sAGE (p < 0.05), doubled uAGE excretion (p < 0.05), and decreased UA (p < 0.01). In addition, LZ maintained normal sAGE in normal rats infused with AGE-BSA, as it doubled the urinary AGE (uAGE) clearance (p < 0.01). B) LZ stimulated the uptake and degradation of (125) I-labeled AGE-BSA and (25) I-human serum AGE by Mf, while suppressing AGE-induced TNFalpha and IGF-I production. In MC, LZ suppressed the AGE-promoted PDGF-B, alpha1 type IV collagen, and tenascin mRNA levels, and restored the AGE-suppressed expression and activity of MMP-9, but not MMP-2. CONCLUSION: LZ may act to: a) accelerate renal in-vivo AGE clearance, b) suppress macrophage and mesangial cell- specific gene activation in vitro, and c) improve albuminuria due to diabetes. These data suggest that LZ by sequestering AGEs may protect against diabetic renal damage. PMID:11788787

  7. Advanced glycation end products (AGEs) on the surface of diabetic erythrocytes bind to the vessel wall via a specific receptor inducing oxidant stress in the vasculature: a link between surface-associated AGEs and diabetic complications.

    PubMed Central

    Wautier, J L; Wautier, M P; Schmidt, A M; Anderson, G M; Hori, O; Zoukourian, C; Capron, L; Chappey, O; Yan, S D; Brett, J

    1994-01-01

    Vascular complications are an important cause of morbidity and mortality in patients with diabetes. The extent of vascular complications has been linked statistically to enhanced adherence of diabetic erythrocytes to endothelial cells (ECs) and to the accumulation of a class of glycated proteins termed advanced glycation end products (AGEs). We hypothesized that formation of AGEs on the surface of diabetic erythrocytes could mediate their interaction with ECs leading to binding and induction of vascular dysfunction. Enhanced binding of diabetic erythrocytes to ECs was blocked by preincubation of erythrocytes with anti-AGE IgG or preincubation of ECs with antibodies to the receptor for AGE (RAGE). Immunoblotting of cultured human ECs and immunostaining of normal/diabetic human tissue confirmed the presence of RAGE in the vessel wall. Binding of diabetic erythrocytes to endothelium generated an oxidant stress, as measured by production of thiobarbituric acid-reactive substances (TBARS) and activation of the transcription factor NF-kappa B, both of which were blocked by probucol or anti-RAGE IgG. Erythrocytes from diabetic rats infused into normal rats had an accelerated, early phase of clearance that was prevented, in part, by antibody to RAGE. Liver tissue from rats infused with diabetic erythrocytes showed elevated levels of TBARS, which was prevented by pretreatment with anti-RAGE IgG or probucol. Thus, erythrocyte surface AGEs can function as ligands that interact with RAGE on endothelium. The extensive contact of diabetic erythrocytes bearing surface-associated AGEs with vessel wall RAGE could be important in the development of vascular complications. Images PMID:8052654

  8. Protein glycation, diabetes, and aging.

    PubMed

    Ulrich, P; Cerami, A

    2001-01-01

    Biological amines react with reducing sugars to form a complex family of rearranged and dehydrated covalent adducts that are often yellow-brown and/or fluorescent and include many cross-linked structures. Food chemists have long studied this process as a source of flavor, color, and texture changes in cooked, processed, and stored foods. During the 1970s and 1980s, it was realized that this process, called the Maillard reaction or advanced glycation, also occurs slowly in vivo. Advanced glycation endproducts (AGEs) that form are implicated, causing the complications of diabetes and aging, primarily via adventitious and crosslinking of proteins. Long-lived proteins such as structural collagen and lens crystallins particularly are implicated as pathogenic targets of AGE processes. AGE formation in vascular wall collagen appears to be an especially deleterious event, causing crosslinking of collagen molecules to each other and to circulating proteins. This leads to plaque formation, basement membrane thickening, and loss of vascular elasticity. The chemistry of these later-stage, glycation-derived crosslinks is still incompletely understood but, based on the hypothesis that AGE formation involves reactive carbonyl groups, the authors introduced the carbonyl reagent aminoguanidine hydrochloride as an inhibitor of AGE formation in vivo in the mid 1980s. Subsequent studies by many researchers have shown the effectiveness of aminoguanidine in slowing or preventing a wide range of complications of diabetes and aging in animals and, recently, in humans. Since, the authors have developed a new class of agents, exemplified by 4,5-dimethyl-3-phenacylthiazolium chloride (DPTC), which can chemically break already-formed AGE protein-protein crosslinks. These agents are based on a new theory of AGE crosslinking that postulates that alpha-dicarbonyl structures are present in AGE protein-protein crosslinks. In studies in aged animals, DPTC has been shown to be capable of reverting

  9. A look inside the diabetic brain: Contributors to diabetes-induced brain aging.

    PubMed

    Wrighten, Shayna A; Piroli, Gerardo G; Grillo, Claudia A; Reagan, Lawrence P

    2009-05-01

    Central nervous system (CNS) complications resulting from diabetes is a problem that is gaining more acceptance and attention. Recent evidence suggests morphological, electrophysiological and cognitive changes, often observed in the hippocampus, in diabetic individuals. Many of the CNS changes observed in diabetic patients and animal models of diabetes are reminiscent of the changes seen in normal aging. The central commonalities between diabetes-induced and age-related CNS changes have led to the theory of advanced brain aging in diabetic patients. This review summarizes the findings of the literature as they relate to the relationship between diabetes and dementia and discusses some of the potential contributors to diabetes-induced CNS impairments.

  10. Immunization of AGE-modified albumin inhibits diabetic nephropathy progression in diabetic mice

    PubMed Central

    Mashitah, Musthika Wida; Azizah, Nurona; Samsu, Nur; Indra, Muhammad Rasjad; Bilal, Muhammad; Yunisa, Meti Verdian; Arisanti, Amildya Dwi

    2015-01-01

    Background Diabetic nephropathy (DN) is a serious vascular complication of diabetes and an important cause of end-stage renal disease. One mechanism by which hyperglycemia causes nephropathy is through the formation of advanced glycation end products (AGE). Development of vaccination would be a promising therapy for the future, while to date, anti-AGE therapy is based on medicines that are needed to be consumed lifelong. This study aimed to find out the effect of immunization of AGE-modified albumin against DN pathogenesis in streptozotocin-induced diabetic in mice. Methods We used 24 BALB/c male mice as experimental animals, which were divided into six groups, two nondiabetic groups (negative control and AGE-modified bovine serum albumin [BSA] preimmunized groups) and four streptozotocin-induced diabetic groups (diabetic control group and diabetic preimmunized groups for AGE-BSA, Keyhole limpet hemocyanin (KLH), and AGE-BSA-KLH, respectively). Results Diabetic preimmunized groups for AGE-BSA, KLH, and AGE-BSA-KLH showed amelioration in renal function and histopathology compared with the diabetic control group. Preimmunization also maintained nephrin intensity and decreased serum AGE level, kidney AGE deposition, and kidney cells apoptosis. Conclusion AGE-BSA and AGE-BSA-KLH immunizations inhibit the progression of DN. Our results strengthen the evidence that the anti-AGE antibodies have a protective role against diabetic vascular complication, especially DN. This study provides a basis for the development of DN-based immunotherapy with AGE immunization as a potential candidate. PMID:26346342

  11. AGE restriction in diabetes mellitus: a paradigm shift.

    PubMed

    Vlassara, Helen; Striker, Gary E

    2011-05-24

    Persistently elevated oxidative stress and inflammation precede or occur during the development of type 1 or type 2 diabetes mellitus and precipitate devastating complications. Given the rapidly increasing incidence of diabetes mellitus and obesity in the space of a few decades, new genetic mutations are unlikely to be the cause, instead pointing to environmental initiators. A hallmark of contemporary culture is a preference for thermally processed foods, replete with pro-oxidant advanced glycation endproducts (AGEs). These molecules are appetite-increasing and, thus, efficient enhancers of overnutrition (which promotes obesity) and oxidant overload (which promotes inflammation). Studies of genetic and nongenetic animal models of diabetes mellitus suggest that suppression of host defenses, under sustained pressure from food-derived AGEs, may potentially shift homeostasis towards a higher basal level of oxidative stress, inflammation and injury of both insulin-producing and insulin-responsive cells. This sequence promotes both types of diabetes mellitus. Reducing basal oxidative stress by AGE restriction in mice, without energy or nutrient change, reinstates host defenses, alleviates inflammation, prevents diabetes mellitus, vascular and renal complications and extends normal lifespan. Studies in healthy humans and in those with diabetes mellitus show that consumption of high amounts of food-related AGEs is a determinant of insulin resistance and inflammation and that AGE restriction improves both. This Review focuses on AGEs as novel initiators of oxidative stress that precedes, rather than results from, diabetes mellitus. Therapeutic gains from AGE restriction constitute a paradigm shift.

  12. (Pre)diabetes, brain aging, and cognition.

    PubMed

    S Roriz-Filho, Jarbas; Sá-Roriz, Ticiana M; Rosset, Idiane; Camozzato, Ana L; Santos, Antonio C; Chaves, Márcia L F; Moriguti, Júlio César; Roriz-Cruz, Matheus

    2009-05-01

    Cognitive dysfunction and dementia have recently been proven to be common (and underrecognized) complications of diabetes mellitus (DM). In fact, several studies have evidenced that phenotypes associated with obesity and/or alterations on insulin homeostasis are at increased risk for developing cognitive decline and dementia, including not only vascular dementia, but also Alzheimer's disease (AD). These phenotypes include prediabetes, diabetes, and the metabolic syndrome. Both types 1 and 2 diabetes are also important risk factors for decreased performance in several neuropsychological functions. Chronic hyperglycemia and hyperinsulinemia primarily stimulates the formation of Advanced Glucose Endproducts (AGEs), which leads to an overproduction of Reactive Oxygen Species (ROS). Protein glycation and increased oxidative stress are the two main mechanisms involved in biological aging, both being also probably related to the etiopathogeny of AD. AD patients were found to have lower than normal cerebrospinal fluid levels of insulin. Besides its traditional glucoregulatory importance, insulin has significant neurothrophic properties in the brain. How can clinical hyperinsulinism be a risk factor for AD whereas lab experiments evidence insulin to be an important neurothrophic factor? These two apparent paradoxal findings may be reconciliated by evoking the concept of insulin resistance. Whereas insulin is clearly neurothrophic at moderate concentrations, too much insulin in the brain may be associated with reduced amyloid-beta (Abeta) clearance due to competition for their common and main depurative mechanism - the Insulin-Degrading Enzyme (IDE). Since IDE is much more selective for insulin than for Abeta, brain hyperinsulinism may deprive Abeta of its main clearance mechanism. Hyperglycemia and hyperinsulinemia seems to accelerate brain aging also by inducing tau hyperphosphorylation and amyloid oligomerization, as well as by leading to widespread brain microangiopathy

  13. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes.

    PubMed

    Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

    2008-01-01

    Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs. PMID:18840258

  14. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes

    PubMed Central

    Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

    2008-01-01

    Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs. PMID:18840258

  15. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes.

    PubMed

    Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

    2008-10-07

    Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.

  16. Dietary Advanced Glycation End Products and Aging

    PubMed Central

    Luevano-Contreras, Claudia; Chapman-Novakofski, Karen

    2010-01-01

    Advanced glycation end products (AGEs) are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food) and endogenously (in humans) with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer’s disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research. PMID:22254007

  17. RECENT ADVANCES IN CHILDHOOD DIABETES MELLITUS

    PubMed Central

    Ayoola, O.O.

    2008-01-01

    Diabetes mellitus (DM) is a syndrome characterized by disturbed metabolism of carbohydrate, protein, and fat. It is a chronic metabolic disorder caused by an absolute or relative deficiency of insulin. It presents with very different medical and psychosocial issues in children. Epidemiological studies indicate that there is gradual but steady increase in the incidence of both type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in both developed and developing countries. The manifestations, therapy goals, clinical course, susceptibility to complications of diabetes differ among childhood cases. T1DM accounts for the majority of cases of diabetes in children. Diabetic ketoacidosis may be the initial presentation of T1DM in many children particularly in Africa probably due to low level of awareness. The focus of this review on T1DM is to provide an overview of the major advances in the aetiology, pathogenesis, and clinical management of newly diagnosed children and their subsequent management with the aim of ensuring optimal growth and development as well as preventing acute and chronic complications. The advances in insulin therapy and regimens and the presentation and management of diabetic ketoacidosis are discussed. The prospects for the cure of the disease are also highlighted in this review. PMID:25161448

  18. Semaphorin3a Promotes Advanced Diabetic Nephropathy

    PubMed Central

    Aggarwal, Pardeep K.; Veron, Delma; Thomas, David B.; Siegel, Dionicio; Moeckel, Gilbert; Kashgarian, Michael

    2015-01-01

    The onset of diabetic nephropathy (DN) is highlighted by glomerular filtration barrier abnormalities. Identifying pathogenic factors and targetable pathways driving DN is crucial to developing novel therapies and improving the disease outcome. Semaphorin3a (sema3a) is a guidance protein secreted by podocytes. Excess sema3a disrupts the glomerular filtration barrier. Here, using immunohistochemistry, we show increased podocyte SEMA3A in renal biopsies from patients with advanced DN. Using inducible, podocyte-specific Sema3a gain-of-function (Sema3a+) mice made diabetic with streptozotocin, we demonstrate that sema3a is pathogenic in DN. Diabetic Sema3a+ mice develop massive proteinuria, renal insufficiency, and extensive nodular glomerulosclerosis, mimicking advanced DN in humans. In diabetic mice, Sema3a+ exacerbates laminin and collagen IV accumulation in Kimmelstiel-Wilson-like glomerular nodules and causes diffuse podocyte foot process effacement and F-actin collapse via nephrin, αvβ3 integrin, and MICAL1 interactions with plexinA1. MICAL1 knockdown and sema3a inhibition render podocytes not susceptible to sema3a-induced shape changes, indicating that MICAL1 mediates sema3a-induced podocyte F-actin collapse. Moreover, sema3a binding inhibition or podocyte-specific plexinA1 deletion markedly ameliorates albuminuria and abrogates renal insufficiency and the diabetic nodular glomerulosclerosis phenotype of diabetic Sema3a+ mice. Collectively, these findings indicate that excess sema3a promotes severe diabetic nephropathy and identifies novel potential therapeutic targets for DN. PMID:25475434

  19. Diabetes and Altered Glucose Metabolism with Aging

    PubMed Central

    Kalyani, Rita Rastogi; Egan, Josephine M.

    2013-01-01

    I. Synopsis Diabetes and impaired glucose tolerance affect a substantial proportion of older adults. While the aging process can be associated with alterations in glucose metabolism, including both relative insulin resistance and islet cell dysfunction, abnormal glucose metabolism is not a necessary component of aging. Instead, older adults with diabetes and altered glucose status likely represent a vulnerable subset of the population at high-risk for complications and adverse geriatric syndromes such as accelerated muscle loss, functional disability, frailty, and early mortality. Goals for treatment of diabetes in the elderly include control of hyperglycemia, prevention and treatment of diabetic complications, avoidance of hypoglycemia and preservation of quality of life. Given the heterogeneity of the elderly population with regards to the presence of comorbidities, life expectancy, and functional status, an individualized approach to diabetes management is often appropriate. A growing area of research seeks to explore associations of dysglycemia and insulin resistance with the development of adverse outcomes in the elderly and may ultimately inform guidelines on the use of future glucose-lowering therapies in this population. PMID:23702405

  20. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications.

    PubMed

    Nagai, Ryoji; Murray, David B; Metz, Thomas O; Baynes, John W

    2012-03-01

    This article outlines evidence that advanced glycation end product (AGE) inhibitors and breakers act primarily as chelators, inhibiting metal-catalyzed oxidation reactions that catalyze AGE formation. We then present evidence that chelation is the most likely mechanism by which ACE inhibitors, angiotensin receptor blockers, and aldose reductase inhibitors inhibit AGE formation in diabetes. Finally, we note several recent studies demonstrating therapeutic benefits of chelators for diabetic cardiovascular and renal disease. We conclude that chronic, low-dose chelation therapy deserves serious consideration as a clinical tool for prevention and treatment of diabetes complications.

  1. Diabetes Drug Victoza Might Not Help Advanced Heart Failure Patients

    MedlinePlus

    ... html Diabetes Drug Victoza Might Not Help Advanced Heart Failure Patients Study participants may have been too sick ... to improve heart function in patients with advanced heart failure, a new study finds. The theory for this ...

  2. Epidemiology of diabetes mellitus in old age in Japan.

    PubMed

    Nakano, Tadasumi; Ito, Hideki

    2007-09-01

    Epidemiological studies on diabetes mellitus revealed that the number of patients with diabetes mellitus is gradually increasing in Japan along with development of car society and westernization of food intake. Since prevalence of diabetes mellitus increases with aging, proportion of individuals with diabetes mellitus aged over 60 has exceeded two-third of estimated total number of patients (7.40 million in 2002) in Japan where aging of society is rapidly progressing. Type 2 diabetes mellitus is common in diabetes mellitus in old age, and there are rarely elderly patients with type 1 diabetes mellitus. Prevalence of both diabetic microangiopathy and atherosclerotic vascular diseases is higher in the elderly with diabetes mellitus than in the middle-aged with diabetes mellitus. Furthermore, atherosclerotic vascular diseases (ischemic heart disease, cerebro-vascular disease and peripheral vascular disease) are more prevalent in the elderly with diabetes mellitus than in those without diabetes mellitus. Many studies demonstrated that functional declines, i.e. decreases in activities of daily living, physical activity and cognitive function, deteriorated quality of life in the elderly, and functional declines are more prominent in the elderly with diabetes mellitus than in those without diabetes mellitus. In order to clarify how the elderly patients with diabetes mellitus should be treated to maintain their quality of life, a nationwide randomized controlled intervention study using 1173 Japanese elderly patients with diabetes mellitus is now performing. In summary, number of elderly patients with diabetes mellitus is overwhelmingly increasing in Japan as well as in westernized countries. It is necessary for us to treat the elderly with diabetes mellitus to maintain their function and quality of life. PMID:17644210

  3. Skeletal muscle capillary density and microvascular function are compromised with aging and type 2 diabetes.

    PubMed

    Groen, Bart B L; Hamer, Henrike M; Snijders, Tim; van Kranenburg, Janneau; Frijns, Dionne; Vink, Hans; van Loon, Luc J C

    2014-04-15

    Adequate muscle perfusion is required for the maintenance of skeletal muscle mass. Impairments in microvascular structure and/or function with aging and type 2 diabetes have been associated with the progressive loss of skeletal muscle mass. Our objective was to compare muscle fiber type specific capillary density and endothelial function between healthy young men, healthy older men, and age-matched type 2 diabetes patients. Fifteen healthy young men (24 ± 1 yr), 15 healthy older men (70 ± 2 yr), and 15 age-matched type 2 diabetes patients (70 ± 1 yr) were selected to participate in the present study. Whole body insulin sensitivity, muscle fiber type specific capillary density, sublingual microvascular density, and dimension of the erythrocyte-perfused boundary region were assessed to evaluate the impact of aging and/or type 2 diabetes on microvascular structure and function. Whole body insulin sensitivity was significantly lower at a more advanced age, with lowest values reported in the type 2 diabetic patients. In line, skeletal muscle capillary contacts were much lower in the older and older type 2 diabetic patients when compared with the young. Sidestream darkfield imaging showed a significantly greater thickness of the erythrocyte perfused boundary region in the type 2 diabetic patients compared with the young. Skeletal muscle capillary density is reduced with aging and type 2 diabetes and accompanied by impairments in endothelial glycocalyx function, which is indicative of compromised vascular function. PMID:24577061

  4. Childhood diabetes mellitus: recent advances & future prospects.

    PubMed

    Dejkhamron, Prapai; Menon, Ram K; Sperling, Mark A

    2007-03-01

    Diabetes mellitus (DM) is a metabolic disease characterized by absolute or relative insulin deficiency. Absolute deficiency of insulin most commonly results from an autoimmune destruction of insulin producing cells in the pancreas and in general, the term Type 1 DM (T1DM) is used to denote childhood diabetes associated with autoimmunity and absolute insulin deficiency. The term Type 2 DM (T2DM) is used to denote diabetes resulting from a relative deficiency of insulin when insulin secretion is inadequate to overcome co-existent resistance to insulin action on carbohydrate, protein or fat metabolism; T2DM is most commonly associated with the prototypic insulin resistant state of obesity. In the western hemisphere DM is one of the most prevalent chronic diseases in childhood, whereas the incidence of T1DM in developing countries is significantly less than that in the western hemisphere. Epidemiological studies indicate that there is gradual but steady increase in the incidence of both T1DM and T2DM in both developed and developing countries. This review provides an overview of the major advances in our understanding of the aetiology, pathogenesis, and clinical management of DM in children with the focus being on T1DM. Genetic predisposition, environmental causes, and emerging concepts of the pathogenesis of T1DM such as the accelerator hypothesis are discussed. The goals of treating a child with DM are to achieve normal growth and development with prevention of acute and chronic complications of DM. These goals are achieved by co-ordinated care delivered by a multidisciplinary team focusing on insulin administrations, glucose monitoring, meal planning, and screening for complications. Newer insulin analogues ("designer" insulin) and automated methods of delivery via programmable pumps have revolutionized the care of the child with diabetes. Though T1DM cannot yet be prevented, ongoing trials and strategies aimed at modulating the autoimmune response and the

  5. Childhood diabetes mellitus: recent advances & future prospects.

    PubMed

    Dejkhamron, Prapai; Menon, Ram K; Sperling, Mark A

    2007-03-01

    Diabetes mellitus (DM) is a metabolic disease characterized by absolute or relative insulin deficiency. Absolute deficiency of insulin most commonly results from an autoimmune destruction of insulin producing cells in the pancreas and in general, the term Type 1 DM (T1DM) is used to denote childhood diabetes associated with autoimmunity and absolute insulin deficiency. The term Type 2 DM (T2DM) is used to denote diabetes resulting from a relative deficiency of insulin when insulin secretion is inadequate to overcome co-existent resistance to insulin action on carbohydrate, protein or fat metabolism; T2DM is most commonly associated with the prototypic insulin resistant state of obesity. In the western hemisphere DM is one of the most prevalent chronic diseases in childhood, whereas the incidence of T1DM in developing countries is significantly less than that in the western hemisphere. Epidemiological studies indicate that there is gradual but steady increase in the incidence of both T1DM and T2DM in both developed and developing countries. This review provides an overview of the major advances in our understanding of the aetiology, pathogenesis, and clinical management of DM in children with the focus being on T1DM. Genetic predisposition, environmental causes, and emerging concepts of the pathogenesis of T1DM such as the accelerator hypothesis are discussed. The goals of treating a child with DM are to achieve normal growth and development with prevention of acute and chronic complications of DM. These goals are achieved by co-ordinated care delivered by a multidisciplinary team focusing on insulin administrations, glucose monitoring, meal planning, and screening for complications. Newer insulin analogues ("designer" insulin) and automated methods of delivery via programmable pumps have revolutionized the care of the child with diabetes. Though T1DM cannot yet be prevented, ongoing trials and strategies aimed at modulating the autoimmune response and the

  6. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats

    PubMed Central

    Zakaria, Mohamed Naguib; El-Bassossy, Hany M.; Barakat, Waleed

    2015-01-01

    Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs) is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE), AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE) and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS) complications in STZ-induced (50 mg/kg, IP) diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze), neuronal degeneration (Fluoro-Jade staining), AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde). These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications. PMID:26491434

  7. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats.

    PubMed

    Zakaria, Mohamed Naguib; El-Bassossy, Hany M; Barakat, Waleed

    2015-01-01

    Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs) is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE), AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE) and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS) complications in STZ-induced (50 mg/kg, IP) diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze), neuronal degeneration (Fluoro-Jade staining), AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde). These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications. PMID:26491434

  8. The diabetic foot management - recent advance.

    PubMed

    Sinwar, Prabhu Dayal

    2015-03-01

    Diabetic ulceration of the foot represents a major global medical, social and economic problem. It is the commonest major end-point of diabetic complications. Diabetic neuropathy and peripheral vascular disease are the main etiological factors in foot ulceration and may act alone, together, or in combination with other factors such as microvascular disease, biomechanical abnormalities, limited joint mobility and increased susceptibility to infection. In the diabetic foot, distal sensory polyneuropathy is seen most commonly. The advent of insulin overcame the acute problems of ketoacidosis and infection, but could not prevent the vascular and neurological complications. Management of diabetic neuropathic ulcer by appropriate and timely removal of callus, control of infection and reduction of weight bearing forces. Management of diabetic ischaemic foot are medical management, surgical management and percutaneous transluminal angioplasty of stenosed and occluded lower extremity arteries. Foot ulceration in persons with diabetes is the most frequent precursor to amputation. PMID:25638739

  9. DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy

    PubMed Central

    Kaida, Yusuke; Fukami, Kei; Matsui, Takanori; Higashimoto, Yuichiro; Nishino, Yuri; Obara, Nana; Nakayama, Yosuke; Ando, Ryotaro; Toyonaga, Maki; Ueda, Seiji; Takeuchi, Masayoshi; Inoue, Hiroyoshi; Okuda, Seiya; Yamagishi, Sho-ichi

    2013-01-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. We screened DNA aptamer directed against AGEs (AGEs-aptamer) in vitro and examined its effects on renal injury in KKAy/Ta mice, an animal model of type 2 diabetes. Eight-week-old male KKAy/Ta or C57BL/6J mice received continuous intraperitoneal infusion of AGEs- or control-aptamer for 8 weeks. AGEs-aptamer was detected and its level was increased in the kidney for at least 7 days. The elimination half-lives of AGEs-aptamer in the kidney were about 7 days. Compared with those in C57BL/6J mice, glomerular AGEs levels were significantly increased in KKAy/Ta mice, which were blocked by AGEs-aptamer. Urinary albumin and 8-hydroxy-2′-deoxy-guanosine levels were increased, and glomerular hypertrophy and enhanced extracellular matrix accumulation were observed in KKAy/Ta mice, all of which were prevented by AGEs-aptamer. Moreover, AGEs-aptamer significantly reduced gene expression of RAGE, monocyte chemoattractant protein-1, connective tissue growth factor, and type IV collagen both in the kidney of KKAy/Ta mice and in AGE-exposed human cultured mesangial cells. Our present data suggest that continuous administration of AGEs-aptamer could protect against experimental diabetic nephropathy by blocking the AGEs-RAGE axis and may be a feasible and promising therapeutic strategy for the treatment of diabetic nephropathy. PMID:23630304

  10. Advanced Glycation End Products: A Molecular Target for Vascular Complications in Diabetes.

    PubMed

    Yamagishi, Sho-Ichi; Nakamura, Nobutaka; Suematsu, Mika; Kaseda, Kuniyoshi; Matsui, Takanori

    2015-10-27

    A nonenzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules and subsequently alters their structural integrity and function. This process has been known to progress at an accelerated rate under hyperglycemic and/or oxidative stress conditions. Over a course of days to weeks, early glycation products undergo further reactions such as rearrangements and dehydration to become irreversibly cross-linked, fluorescent and senescent macroprotein derivatives termed advanced glycation end products (AGEs). There is a growing body of evidence indicating that interaction of AGEs with their receptor (RAGE) elicits oxidative stress generation and as a result evokes proliferative, inflammatory, thrombotic and fibrotic reactions in a variety of cells. This evidence supports AGEs' involvement in diabetes- and aging-associated disorders such as diabetic vascular complications, cancer, Alzheimer's disease and osteoporosis. Therefore, inhibition of AGE formation could be a novel molecular target for organ protection in diabetes. This report summarizes the pathophysiological role of AGEs in vascular complications in diabetes and discusses the potential clinical utility of measurement of serum levels of AGEs for evaluating organ damage in diabetes.

  11. Human umbilical cord blood cells and diabetes mellitus: recent advances.

    PubMed

    Reddi, Alluru S; Kothari, Neil; Kuppasani, Kishore; Ende, Norman

    2015-01-01

    Stem cell therapy for patients with diabetes is an area of great interest to both scientists and clinicians. Human umbilical cord blood cells (HUCBCs) are being increasingly used as a source of stem cells for cell-based therapy for diabetes because these cells can differentiate into pancreatic islet β-cells. Administration of HUCBCs has been shown to lower blood glucose levels in diabetic animal models. The use of autologous HUCBC transfusion in type 1 diabetic children has not shown any benefit. However, "Stem Cell Educator" therapy has shown promise in long term lowering of blood glucose levels in both type 1 and type 2 diabetic patients. In this review, we will briefly discuss recent advances in HUCBC therapy in the treatment of diabetes and some of its complications.

  12. Advanced Glycation End Products: A Molecular Target for Vascular Complications in Diabetes

    PubMed Central

    Yamagishi, Sho-ichi; Nakamura, Nobutaka; Suematsu, Mika; Kaseda, Kuniyoshi; Matsui, Takanori

    2015-01-01

    A nonenzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules and subsequently alters their structural integrity and function. This process has been known to progress at an accelerated rate under hyperglycemic and/or oxidative stress conditions. Over a course of days to weeks, early glycation products undergo further reactions such as rearrangements and dehydration to become irreversibly cross-linked, fluorescent and senescent macroprotein derivatives termed advanced glycation end products (AGEs). There is a growing body of evidence indicating that interaction of AGEs with their receptor (RAGE) elicits oxidative stress generation and as a result evokes proliferative, inflammatory, thrombotic and fibrotic reactions in a variety of cells. This evidence supports AGEs’ involvement in diabetes- and aging-associated disorders such as diabetic vascular complications, cancer, Alzheimer’s disease and osteoporosis. Therefore, inhibition of AGE formation could be a novel molecular target for organ protection in diabetes. This report summarizes the pathophysiological role of AGEs in vascular complications in diabetes and discusses the potential clinical utility of measurement of serum levels of AGEs for evaluating organ damage in diabetes. PMID:26605646

  13. Receptor for advanced glycation end products (RAGE): a novel therapeutic target for diabetic vascular complication.

    PubMed

    Yamagishi, Sho-ichi; Nakamura, Kazuo; Matsui, Takanori; Noda, Yoshihiro; Imaizumi, Tsutomu

    2008-01-01

    Diabetic vascular complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Although several hyperglycemia-elicited metabolic and hemodynamic derangements have been implicated in the pathogenesis of diabetic vascular complication, the process of formation and accumulation of advanced glycation end products (AGEs) and their mode of action are most compatible with the theory 'hyperglycemic memory'. Further, there is a growing body of evidence that AGEs and their receptor (RAGE) axis is involved in the pathogenesis of diabetic vascular complication. Indeed, the engagement of RAGE with AGEs is shown to elicit oxidative stress generation and subsequently evoke inflammatory responses in various types of cells, thus playing an important role in the development and progression of diabetic micro- and macroangiopathy. These observations suggest that down-regulation of RAGE expression or blockade of the RAGE downstream signaling may be a promising target for therapeutic intervention in diabetic vascular complication. In this review, we discuss several types of agents that could potentially inhibit RAGE expression or its downstream pathways and their therapeutic implications in diabetic vascular complication. PMID:18289075

  14. Recent advances in nanotechnology for diabetes treatment.

    PubMed

    DiSanto, Rocco Michael; Subramanian, Vinayak; Gu, Zhen

    2015-01-01

    Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to 'closed-loop' insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels (BGLs). 'Closing the loop' between BGL measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed.

  15. Recent Advances in Nanotechnology for Diabetes Treatment

    PubMed Central

    DiSanto, Rocco Michael; Subramanian, Vinayak; Gu, Zhen

    2015-01-01

    Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to “closed-loop” insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels. “Closing the loop” between blood glucose level (BGL) measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed. PMID:25641955

  16. Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications

    SciTech Connect

    Nagai, Rhoji; Murray, David B.; Metz, Thomas O.; Baynes, John

    2012-03-01

    Advanced glycation or glycoxidation end-products (AGE) increase in tissue proteins with age, and their rate of accumulation is increased in diabetes, nephropathy and inflammatory diseases. AGE inhibitors include a range of compounds that are proposed to act by trapping carbonyl and dicarbonyl intermediates in AGE formation. However, some among the newer generation of AGE inhibitors lack reactive functional groups that would trap reaction intermediates, indicating an alternative mechanism of action. We propose that AGE inhibitors function primarily as chelators, inhibiting metal-catalyzed oxidation reactions. The AGE-inhibitory activity of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is also consistent with their chelating activity. Finally, compounds described as AGE breakers, or their hydrolysis products, also have strong chelating activity, suggesting that these compounds also act through their chelating activity. We conclude that chelation is the common, and perhaps the primary, mechanism of action of AGE inhibitors and breakers, and that chronic, mild chelation therapy should prove useful in treatment of diabetes and age-related diseases characterized by oxidative stress, inflammation and increased chemical modification of tissue proteins by advanced glycoxidation and lipoxidation end-products.

  17. Clinical applications of advanced lipoprotein testing in diabetes mellitus

    PubMed Central

    Moin, Danyaal S; Rohatgi, Anand

    2011-01-01

    Traditional lipid profiles often fail to fully explain the elevated cardiovascular risk of individuals with diabetes mellitus. Advanced lipoprotein testing offers a novel means to evaluate dyslipidemia and refine risk estimation. Numerous observational studies have demonstrated a characteristic pattern of elevated levels of small, dense LDL particles, out of proportion to traditional lipid levels, in patients with both diabetes mellitus and the metabolic syndrome. Commonly used glucose and lipid-lowering agents have varied effects in patients with diabetes on both LDL and HDL subfractions. The exact role of advanced lipoprotein testing in patients with diabetes mellitus and the metabolic syndrome remains unclear but may offer improved assessment of cardiovascular risk compared with traditional lipid measurements. PMID:22162979

  18. Advancing Paternal Age and Simplex Autism

    ERIC Educational Resources Information Center

    Puleo, Connor Morrow; Schmeidler, James; Reichenberg, Abraham; Kolevzon, Alexander; Soorya, Latha V.; Buxbaum, Joseph D.; Silverman, Jeremy M.

    2012-01-01

    De novo events appear more common in female and simplex autism spectrum disorder (ASD) cases and may underlie greater ASD risk in older fathers' offspring. This study examined whether advancing paternal age predicts an increase in simplex (n = 90) versus multiplex ASD cases (n = 587) in 677 participants (340 families). Whether or not controlling…

  19. Receptor for Advanced Glycation End Products (RAGE) Deficiency Attenuates the Development of Atherosclerosis in Diabetes

    PubMed Central

    Soro-Paavonen, Aino; Watson, Anna M.D.; Li, Jiaze; Paavonen, Karri; Koitka, Audrey; Calkin, Anna C.; Barit, David; Coughlan, Melinda T.; Drew, Brian G.; Lancaster, Graeme I.; Thomas, Merlin; Forbes, Josephine M.; Nawroth, Peter P.; Bierhaus, Angelika; Cooper, Mark E.; Jandeleit-Dahm, Karin A.

    2008-01-01

    OBJECTIVE—Activation of the receptor for advanced glycation end products (RAGE) in diabetic vasculature is considered to be a key mediator of atherogenesis. This study examines the effects of deletion of RAGE on the development of atherosclerosis in the diabetic apoE−/− model of accelerated atherosclerosis. RESEARCH DESIGN AND METHODS—ApoE−/− and RAGE−/−/apoE−/− double knockout mice were rendered diabetic with streptozotocin and followed for 20 weeks, at which time plaque accumulation was assessed by en face analysis. RESULTS—Although diabetic apoE−/− mice showed increased plaque accumulation (14.9 ± 1.7%), diabetic RAGE−/−/apoE−/− mice had significantly reduced atherosclerotic plaque area (4.9 ± 0.4%) to levels not significantly different from control apoE−/− mice (4.3 ± 0.4%). These beneficial effects on the vasculature were associated with attenuation of leukocyte recruitment; decreased expression of proinflammatory mediators, including the nuclear factor-κB subunit p65, VCAM-1, and MCP-1; and reduced oxidative stress, as reflected by staining for nitrotyrosine and reduced expression of various NADPH oxidase subunits, gp91phox, p47phox, and rac-1. Both RAGE and RAGE ligands, including S100A8/A9, high mobility group box 1 (HMGB1), and the advanced glycation end product (AGE) carboxymethyllysine were increased in plaques from diabetic apoE−/− mice. Furthermore, the accumulation of AGEs and other ligands to RAGE was reduced in diabetic RAGE−/−/apoE−/− mice. CONCLUSIONS—This study provides evidence for RAGE playing a central role in the development of accelerated atherosclerosis associated with diabetes. These findings emphasize the potential utility of strategies targeting RAGE activation in the prevention and treatment of diabetic macrovascular complications. PMID:18511846

  20. Characterization of hearing loss in aged type II diabetics.

    PubMed

    Frisina, Susan T; Mapes, Frances; Kim, SungHee; Frisina, D Robert; Frisina, Robert D

    2006-01-01

    Presbycusis - age-related hearing loss - is the number one communicative disorder and a significant chronic medical condition of the aged. Little is known about how type II diabetes, another prevalent age-related medical condition, and presbycusis interact. The present investigation aimed to comprehensively characterize the nature of hearing impairment in aged type II diabetics. Hearing tests measuring both peripheral (cochlea) and central (brainstem and cortex) auditory processing were utilized. The majority of differences between the hearing abilities of the aged diabetics and their age-matched controls were found in measures of inner ear function. For example, large differences were found in pure-tone audiograms, wideband noise and speech reception thresholds, and otoacoustic emissions. The greatest deficits tended to be at low frequencies. In addition, there was a strong tendency for diabetes to affect the right ear more than the left. One possible interpretation is that as one develops presbycusis, the right ear advantage is lost, and this decline is accelerated by diabetes. In contrast, auditory processing tests that measure both peripheral and central processing showed fewer declines between the elderly diabetics and the control group. Consequences of elevated blood sugar levels as possible underlying physiological mechanisms for the hearing loss are discussed.

  1. [Advances in arterial hypertension and diabetes mellitus].

    PubMed

    Cordero, Alberto; Lekuona, Iñaki; Galve, Enrique; Mazón, Pilar

    2012-01-01

    In 2011, the importance of hypertension and diabetes mellitus as the two main risk factors responsible for the development of cardiovascular disease became clear, as did their significance as major public health issues. Compared with previous years, in which publication of the results of large clinical trials dominated scientific progress, in the last year, the focus has shifted to evidence that novel mechanisms associated with blood pressure, glucose metabolism and diabetes can influence cardiovascular disease. Of particular importance were clinical trials in the area of renal dysfunction, such as the SHARP and ROADMAP trials.

  2. Depletion of reactive advanced glycation endproducts from diabetic uremic sera using a lysozyme-linked matrix.

    PubMed Central

    Mitsuhashi, T; Li, Y M; Fishbane, S; Vlassara, H

    1997-01-01

    Diabetic uremic sera contain excessive amounts of reactive advanced glycation endproducts (AGEs), which accelerate the vasculopathy of diabetes and end-stage renal disease. To capture in vivo-derived toxic AGEs, high affinity AGE-binding protein lysozyme (LZ) was linked to a Sepharose 4B matrix. Initial studies showed that > 80% of 125I-AGE-BSA was retained by the LZ matrix, compared with < 10% retained by a control matrix. More than 60% of AGE-lysine was captured by the LZ matrix, and the LZ-bound fraction retained immunoreactivity and cross-linking activity, but had little intrinsic fluorescence (370/440 nm). After passage through the LZ matrix, AGE levels in diabetic sera (0.37+/-0.04 U/mg) were significantly reduced to a level (0.09+/-0.01 U/mg; n = 10; P < 0. 0001) comparable with the level of normal human serum, whereas total protein absorption was < 3%. The AGE-enriched serum fraction exhibited cross-linking activity, which was completely prevented by aminoguanidine. Among numerous LZ-bound proteins in diabetic uremic sera, three major proteins "susceptible" to AGE modification were identified: the immunoglobulin G light chain, apolipoprotein J (clusterin/SP-40,40), and the complement 3b beta chain. These findings indicate that the LZ-linked AGE affinity column may serve as an efficient method for the depletion of toxic AGEs from sera, including specific AGE-modified proteins that may be linked to altered immunity, lipoprotein metabolism, and accelerated vasculopathy in renal failure patients with or without diabetes. PMID:9259584

  3. The Extract of Aster Koraiensis Prevents Retinal Pericyte Apoptosis in Diabetic Rats and Its Active Compound, Chlorogenic Acid Inhibits AGE Formation and AGE/RAGE Interaction

    PubMed Central

    Kim, Junghyun; Jo, Kyuhyung; Lee, Ik-Soo; Kim, Chan-Sik; Kim, Jin Sook

    2016-01-01

    Retinal capillary cell loss is a hallmark of early diabetic retinal changes. Advanced glycation end products (AGEs) are believed to contribute to retinal microvascular cell loss in diabetic retinopathy. In this study, the protective effects of Aster koraiensis extract (AKE) against damage to retinal vascular cells were investigated in streptozotocin (STZ)-induced diabetic rats. To examine this issue further, AGE accumulation, nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) were investigated using retinal trypsin digests from streptozotocin-induced diabetic rats. In the diabetic rats, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling)-positive retinal microvascular cells were markedly increased. Immunohistochemical studies revealed that AGEs were accumulated within the retinal microvascular cells, and this accumulation paralleled the activation of NF-κB and the expression of iNOS in the diabetic rats. However, AKE prevented retinal microvascular cell apoptosis through the inhibition of AGE accumulation and NF-κB activation. Moreover, to determine the active compounds of AKE, two major compounds, chlorogenic acid and 3,5-di-O-caffeoylquinic acid, were tested in an in vitro assay. Among these compounds, chlorogenic acid significantly reduced AGE formation as well as AGE/RAGE (receptor for AGEs) binding activity. These results suggest that AKE, particularly chlorogenic acid, is useful in inhibiting AGE accumulation in retinal vessels and exerts a preventive effect against the injuries of diabetic retinal vascular cells. PMID:27657123

  4. Cardiovascular KATP channels and advanced aging

    PubMed Central

    Yang, Hua-Qian; Subbotina, Ekaterina; Ramasamy, Ravichandran; Coetzee, William A.

    2016-01-01

    With advanced aging, there is a decline in innate cardiovascular function. This decline is not general in nature. Instead, specific changes occur that impact the basic cardiovascular function, which include alterations in biochemical pathways and ion channel function. This review focuses on a particular ion channel that couple the latter two processes, namely the KATP channel, which opening is promoted by alterations in intracellular energy metabolism. We show that the intrinsic properties of the KATP channel changes with advanced aging and argue that the channel can be further modulated by biochemical changes. The importance is widespread, given the ubiquitous nature of the KATP channel in the cardiovascular system where it can regulate processes as diverse as cardiac function, blood flow and protection mechanisms against superimposed stress, such as cardiac ischemia. We highlight questions that remain to be answered before the KATP channel can be considered as a viable target for therapeutic intervention. PMID:27733235

  5. Comparison of Age of Onset and Frequency of Diabetic Complications in the Very Elderly Patients with Type 2 Diabetes

    PubMed Central

    2016-01-01

    Background The prevalence of type 2 diabetes in elderly people has increased dramatically in the last few decades. This study was designed to clarify the clinical characteristics of type 2 diabetes in patients aged ≥80 years according to age of onset. Methods We reviewed the medical records of 289 patients aged ≥80 years with type 2 diabetes at the outpatient diabetes clinics of Kangwon National University Hospital from September 2010 to June 2014. We divided the patients into middle-age-onset diabetes (onset before 65 years of age) and elderly-onset diabetes (onset at 65+ years of age). Results There were 141 male and 148 female patients. The patients had a mean age of 83.2±2.9 years and the mean duration of diabetes was 14.3±10.4 years. One hundred and ninety-nine patients had elderly-onset diabetes. The patients with elderly-onset diabetes had a significantly lower frequency of diabetic retinopathy and nephropathy, lower serum creatinine levels, lower glycated hemoglobin (HbA1c) levels, and similar coronary revascularization and cerebral infarction rates compared to those with middle-age-onset diabetes. There was no frequency difference in coronary revascularization and cerebral infarction and HbA1c levels between three subgroups (<5, 5 to 15, and ≥15 years) of diabetes duration in elderly onset diabetes. However, both in the elderly onset diabetes and middle-age-onset diabetes, the cumulative incidence of retinopathy was increasing rapidly according to the duration of diabetes. Conclusion We report that individuals with elderly-onset diabetes have a lower frequency of diabetic retinopathy and nephropathy and similar cardiovascular complications compared to those with middle-age-onset diabetes. PMID:27586451

  6. Recent advances in type 1 diabetes.

    PubMed

    Kyi, Mervyn; Wentworth, John M; Nankervis, Alison J; Fourlanos, Spiros; Colman, Peter G

    2015-10-01

    Type 1 diabetes (T1D) is caused by an autoimmune attack on pancreatic beta cells that leads to insulin deficiency. The incidence of T1D in Australia has doubled over the past 20 years. T1D treatment focuses on physiological insulin replacement, aiming for near-normal blood glucose levels. Hypoglycaemia is a significant cause of morbidity and mortality in T1D. Optimal T1D management is complex, and is enhanced by empowering individuals in all aspects of managing diabetes. New technologies, including insulin pumps, continuous glucose monitors and sensor-augmented pumps, can assist people achieve better glycaemic control and reduce the risk of severe hypoglycaemia. Women with T1D can achieve significantly better outcomes during pregnancy and for their infants by planning for their pregnancy and by intensive glycaemic control. Several trials are underway that seek to identify the determinants of autoimmunity and to develop therapies that prevent T1D in at-risk individuals. Pancreatic and islet cell transplants are proven therapies, but are only offered to individuals with diabetes and renal failure (pancreas) or severe hypoglycaemia unawareness (islet cell transplants). Although T1D is still associated with considerable premature mortality, recent findings show that a significant improvement in life expectancy has occurred. PMID:26424063

  7. The renin-angiotensin system and advanced glycation end-products in diabetic retinopathy: impacts and synergies.

    PubMed

    Miller, Antonia G; Zhu, Tong; Wilkinson-Berka, Jennifer L

    2013-11-01

    Diabetic retinopathy is a major cause of vision impairment and blindness and represents a significant health burden throughout the world. There is considerable interest in developing new treatments that retard the progression of diabetic retinopathy from its early to proliferative stages. It could be argued that the absence of an ideal therapy for diabetic retinopathy comes from an incomplete understanding about the biochemical mechanisms that underlie this disease, and their precise impact on specific retinal cell populations. Findings from pre-clinical and clinical studies indicate that both the renin-angiotensin system (RAS) and advanced glycation end-products (AGEs) influence various aspects of diabetic retinopathy. Of interest is growing evidence of cross-talk between the RAS and AGEs pathways. This review will discuss the role of both the RAS and AGEs in diabetic retinopathy, and how the identification of interactions between the two pathways may have implications for the development of new treatment strategies. PMID:23173957

  8. Self–reported diabetes education among Chinese middle–aged and older adults with diabetes

    PubMed Central

    Xu, Hanzhang; Luo, Jianfeng; Wu, Bei

    2016-01-01

    Background To compare self–reported diabetes education among Chinese middle–aged and older adults with diabetes in three population groups: urban residents, migrants in urban settings, and rural residents. Methods We used data from the 2011 China Health and Retirement Longitudinal Study. The sample included 993 participants age 45 and older who reported having diabetes diagnosed from a health professional. We performed multilevel regressions performed to examine the associations between characteristics and different aspects of diabetes education received. Findings Our study shows that 20.24% of the participants received no diabetes education at all. Among those who received information, 46.82% of respondents with diabetes received weight control advice from a health care provider, 90.97% received advice on exercise, 60.37% received diet advice, 35.12% were spoken to smoking control, and only 17.89% of persons were informed of foot care. After controlling socioeconomic factors, life style, number of comorbidities and community factors, we found that compared with migrant population and rural residents, urban residents were more likely to receive diabetes education on diet. Urban residents were also more likely to obtain diabetes education and more aspects of diabetes education comparison with migrants and rural residents. Conclusions Our study suggests diabetes education is a serious concern in China, and a significant proportion of the participants did not receive advice on smoking control and foot care. Rural residents and migrants from rural areas received much less diabetes education compared with urban residents. Efforts to improve diabetes educations are urgently needed in China.

  9. Advances in retinal imaging for diabetic retinopathy and diabetic macular edema.

    PubMed

    Tan, Colin Siang Hui; Chew, Milton Cher Yong; Lim, Louis Wei Yi; Sadda, Srinivas R

    2016-01-01

    Diabetic retinopathy and diabetic macular edema (DME) are leading causes of blindness throughout the world, and cause significant visual morbidity. Ocular imaging has played a significant role in the management of diabetic eye disease, and the advent of advanced imaging modalities will be of great value as our understanding of diabetic eye diseases increase, and the management options become increasingly varied and complex. Color fundus photography has established roles in screening for diabetic eye disease, early detection of progression, and monitoring of treatment response. Fluorescein angiography (FA) detects areas of capillary nonperfusion, as well as leakage from both microaneurysms and neovascularization. Recent advances in retinal imaging modalities complement traditional fundus photography and provide invaluable new information for clinicians. Ultra-widefield imaging, which can be used to produce both color fundus photographs and FAs, now allows unprecedented views of the posterior pole. The pathologies that are detected in the periphery of the retina have the potential to change the grading of disease severity, and may be of prognostic significance to disease progression. Studies have shown that peripheral ischemia may be related to the presence and severity of DME. Optical coherence tomography (OCT) provides structural detail of the retina, and the quantitative and qualitative features are useful in the monitoring of diabetic eye disease. A relatively recent innovation, OCT angiography, produces images of the fine blood vessels at the macula and optic disc, without the need for contrast agents. This paper will review the roles of each of these imaging modalities for diabetic eye disease.

  10. Epidemiology of fracture risk with advancing age.

    PubMed

    Ensrud, Kristine E

    2013-10-01

    Bone loss and structural damage with advancing age lead to skeletal fragility as manifested by low bone mass and deficits in bone geometry, microarchitecture, and material properties. Skeletal fragility, in combination with a greater propensity to fall, results in an increased susceptibility to fractures with aging, known as fragility fractures. Fragility fractures exceed 2 million per year in number and account for nearly 20 billion dollars per year in health care costs in the United States. Advanced age, low bone mass, and previous fracture are strong risk factors for fractures at nearly all skeletal sites, but each type of fracture also has its own set of unique risk factors. Hip fractures are most strongly associated with adverse consequences, but these account for only a minority of fragility fractures. Vertebral fractures comprise the most common manifestation of fragility fracture, but the majority of these fractures are asymptomatic. Most research has focused on the epidemiology of fractures at the hip, vertebrae, and wrist and less is known about other fracture types, which account for 40% of total fragility fractures that are clinically recognized. Future research focused on identification of older adults at high risk of disabling fractures is warranted. PMID:23833201

  11. Antihyperglycemic activity and inhibition of advanced glycation end product formation by Cuminum cyminum in streptozotocin induced diabetic rats.

    PubMed

    Jagtap, A G; Patil, P B

    2010-01-01

    Cuminum cyminum is widely used as a spice in many countries. The aim of the present study was to investigate the effect of methanolic extract of seeds of C. cyminum (CC) on diabetes, oxidative stress and formation of advanced glycated end products (AGE) and obtain comparison with glibenclamide. In vitro studies indicated that CC inhibited free radicals and AGE formation. Treatment of streptozotocin-diabetic rats with CC and glibenclamide for 28 days caused a reduction in blood glucose, glycosylated hemoglobin, creatinine, blood urea nitrogen and improved serum insulin and glycogen (liver and skeletal muscle) content when compared to diabetic control rats. Significant reduction in renal oxidative stress and AGE was observed with CC when compared to diabetic control and glibenclamide. CC and glibenclamide improved antioxidant status in kidney and pancreas of diabetic rats. Diabetic rats showed increase in rat tail tendon collagen, glycated collagen, collagen linked fluorescence and reduction in pepsin digestion. Treatment with CC significantly improved these parameters when compared to diabetic control and glibenclamide group. Though the antidiabetic effect of CC was comparable to glibenclamide it had better effect in controlling oxidative stress and inhibiting the AGE formation, which are implicated in the pathogenesis of diabetic microvascular complications.

  12. Age, race, diabetes, blood pressure, and mortality among hemodialysis patients.

    PubMed

    Myers, Orrin B; Adams, Christopher; Rohrscheib, Mark R; Servilla, Karen S; Miskulin, Dana; Bedrick, Edward J; Zager, Philip G

    2010-11-01

    Observational studies involving hemodialysis patients suggest a U-shaped relationship between BP and mortality, but the majority of these studies followed large, heterogeneous cohorts. To examine whether age, race, and diabetes status affect the association between systolic BP (SBP; predialysis) and mortality, we studied a cohort of 16,283 incident hemodialysis patients. We constructed a series of multivariate proportional hazards models, adding age and BP to the analyses as cubic polynomial splines to model potential nonlinear relationships with mortality. Overall, low SBP associated with increased mortality, and the association was more pronounced among older patients and those with diabetes. Higher SBP associated with increased mortality among younger patients, regardless of race or diabetes status. We observed a survival advantage for black patients primarily among older patients. Diabetes associated with increased mortality mainly among older patients with low BP. In conclusion, the design of randomized clinical trials to identify optimal BP targets for patients with ESRD should take age and diabetes status into consideration.

  13. Regulation of alcohol intake with advancing age.

    PubMed

    York, James L; Welte, John; Hirsch, Judith

    2005-05-01

    Previous surveys of alcohol use in the general population have not gathered sufficient data to allow for estimations of the blood alcohol levels (BACs) routinely achieved in survey participants. Our goal was to assess the influence of age on the estimated peak BAC achieved on typical drinking occasions in a representative sample (n=2,626) of the U.S. adult population. Variables related to the quantity and duration of alcohol consumption on typical drinking occasions were assessed by computer-assisted telephone interview. In addition, the height, weight, age, and gender of subjects were ascertained to be used in equations to predict the volume of distribution of ethanol (total body water). Prediction equations were used to estimate the probable peak BACs achieved during the typical drinking occasion. The survey identified 1,833 subjects ("current drinkers") of 18-89 years, who reported alcohol consumption within the past 12 months. Linear regression analyses performed on data from these "current drinkers" revealed that, for both men and women, there was an age-related decrease in the predicted peak BAC achieved on typical drinking occasions. The approaches used to modify the BAC with advancing age differed slightly for men and women, but both relied heavily upon a reduction in the quantity of consumption.

  14. Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes.

    PubMed Central

    Bucala, R; Tracey, K J; Cerami, A

    1991-01-01

    Nitric oxide (an endothelium-derived relaxing factor) induces smooth muscle relaxation and is an important mediator in the regulation of vascular tone. Advanced glycosylation end products, the glucose-derived moieties that form nonenzymatically and accumulate on long-lived tissue proteins, have been implicated in many of the complications of diabetes and normal aging. We demonstrate that advanced glycosylation products quench nitric oxide activity in vitro and in vivo. Acceleration of the advanced glycosylation process in vivo results in a time-dependent impairment in endothelium-dependent relaxation. Inhibition of advanced glycosylation with aminoguanidine prevents nitric oxide quenching, and ameliorates the vasodilatory impairment. These results implicate advanced glycosylation products as important modulators of nitric oxide activity and endothelium-dependent relaxation. PMID:1991829

  15. Advanced glycation end products as environmental risk factors for the development of type 1 diabetes.

    PubMed

    Yap, Felicia Y T; Kantharidis, Phillip; Coughlan, Melinda T; Slattery, Robyn; Forbes, Josephine M

    2012-04-01

    The globally rising incidence of Type 1 diabetes (T1D) is no longer restricted to individuals with higher risk genotypes, but is now significantly increasing in a population with lower risk genotypes, likely as the result of environmental factors. In this review, we discuss the potential of advanced glycation end products (AGEs) as environmental contributors to the development of T1D. AGEs are nonenzymatically formed protein modifications found in the body, as well as, consumed in our daily diets. To date, many studies have provided evidence of AGE involvement in β cell dysfunction, whether by AGE modification itself or via interaction with AGE receptors. The receptor for AGE (RAGE) and AGE-receptor-1 (AGE-R1) are of particular interest, given that studies have demonstrated the deleterious effects of RAGE modulation and the protection afforded by AGE-R1 in the context of diabetes. More interestingly, we have recently found that two RAGE polymorphism are predictive of T1D in humans while the third is protective. Moreover, soluble RAGE (sRAGE) levels (a circulating competitive inhibitor of RAGE) were greatly reduced at seroconversion to autoantibodies in both children on high risk of T1D background and in an animal model of autoiummune diabetes. Taken together with the fact that AGEs have also shown to be involved in immunomodulation, it is tempting to postulate that dietary AGEs, RAGE and even AGE-R1 could be working synergistically or independently to breach the tightly regulated immune system, providing a missing link in the development of T1D. PMID:22250649

  16. Microvascular complications and diabetic retinopathy: recent advances and future implications.

    PubMed

    Barot, Megha; Gokulgandhi, Mitan R; Patel, Sulabh; Mitra, Ashim K

    2013-03-01

    Retinal microvascular alterations have been observed during diabetic retinopathy (DR) due to the retinal susceptibility towards subtle pathological alterations. Therefore, retinal microvascular pathology is essential to understand the nature of retinal degenerations during DR. In this review, the role of retinal microvasculature complications during progression of DR, along with recent efforts to normalize such alterations for better therapeutic outcome, will be underlined. In addition, current therapeutics and future directions for advancement of standard treatment for DR patients will be discussed. PMID:23464520

  17. Diabetes prevention: Reproductive age women affected by insulin resistance.

    PubMed

    Rezai, Shadi; LoBue, Stephen; Henderson, Cassandra E

    2016-07-01

    In the United States, 29.1 million people are affected by diabetes, of which 95% have type 2 diabetes. There has been a fivefold increase in type 2 diabetes in the latter half of the 20th century, an increase strongly linked to the obesity epidemic in the United States. In addition, insulin resistance affects 86 million Americans, or more than one-third of the adult population, as manifested by impaired fasting glucose tolerance with random glucose values ranging from ⩾100 to <126 mg/dL. In all, 90% of those affected by impaired fasting glucose tolerance or pre-diabetes are unaware of their metabolic derangement. Although impaired fasting glucose tolerance increases one's risk of developing type 2 diabetes, once identified, application of lifestyle changes by affected individuals may avoid or delay the onset of type 2 diabetes. For reproductive age women who are found to have impaired fasting glucose tolerance, lifestyle changes may be an effective tool to diminish the reproductive health consequences of insulin resistance related diseases. PMID:27638898

  18. Technology Use in Transition-Age Patients With Type 1 Diabetes: Reality and Promises.

    PubMed

    Los, Evan; Ulrich, Jenae; Guttmann-Bauman, Ines

    2016-05-01

    Youth with chronic illnesses have the greatest risk for a decline in their health management during transition-age. Because of this demonstrated and well-known issue, research has focused on how to improve the transition of care process. Despite the increasing number of technological devices on the market and the advances in telemedicine modalities available to patients with type 1 diabetes (T1D), the utilization of technology is still suboptimal among patients of transition-age (ages 13-25). This article reviews the available resources, patterns of use in transition-age youth, and explores opportunities to advance technology use in transitioning patients with T1D from pediatric to adult care. PMID:26892506

  19. Proteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation

    PubMed Central

    Kesavan, Suresh K.; Bhat, Shweta; Golegaonkar, Sandeep B.; Jagadeeshaprasad, Mashanipalya G.; Deshmukh, Arati B.; Patil, Harshal S.; Bhosale, Santosh D.; Shaikh, Mahemud L.; Thulasiram, Hirekodathakallu V.; Boppana, Ramanamurthy; Kulkarni, Mahesh J.

    2013-01-01

    The non-enzymatic reaction between glucose and protein can be chemically reversed by transglycation. Here we report the transglycation activity of hydralazine using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in streptozotocin (STZ) induced diabetic mice, as evidenced by decrease in protein glycation, as well as presence of hydralazine-glucose conjugate in urine of diabetic mice treated with hydralazine. Hydralazine down regulated the expression of Receptor for Advanced Glycation End products (RAGE), NADPH oxidase (NOX), and super oxide dismutase (SOD). These findings will provide a new dimension for developing intervention strategies for the treatment of glycation associated diseases such as diabetes complications, atherosclerosis, and aging. PMID:24126953

  20. Proteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation.

    PubMed

    Kesavan, Suresh K; Bhat, Shweta; Golegaonkar, Sandeep B; Jagadeeshaprasad, Mashanipalya G; Deshmukh, Arati B; Patil, Harshal S; Bhosale, Santosh D; Shaikh, Mahemud L; Thulasiram, Hirekodathakallu V; Boppana, Ramanamurthy; Kulkarni, Mahesh J

    2013-10-15

    The non-enzymatic reaction between glucose and protein can be chemically reversed by transglycation. Here we report the transglycation activity of hydralazine using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in streptozotocin (STZ) induced diabetic mice, as evidenced by decrease in protein glycation, as well as presence of hydralazine-glucose conjugate in urine of diabetic mice treated with hydralazine. Hydralazine down regulated the expression of Receptor for Advanced Glycation End products (RAGE), NADPH oxidase (NOX), and super oxide dismutase (SOD). These findings will provide a new dimension for developing intervention strategies for the treatment of glycation associated diseases such as diabetes complications, atherosclerosis, and aging.

  1. The pecking order of skin Advanced Glycation Endproducts (AGEs) as long-term markers of glycemic damage and risk factors for micro- and subclinical macrovascular disease progression in Type 1 diabetes.

    PubMed

    Monnier, Vincent M; Genuth, Saul; Sell, David R

    2016-08-01

    To date more than 20 glycation products were identified, of which ~15 in the insoluble human skin collagen fraction. The goal of this review is to streamline 30 years of research and ask a set of important questions: in Type 1 diabetes which glycation products correlate best with 1) past mean glycemia 2) reversibility with improved glycemic control, 2) cross-sectional severity of retinopathy, nephropathy and neuropathy and 3) the future long-term risk of progression of micro- and subclinical macrovascular disease. The trio of glycemia related glycation markers furosine (FUR)/fructose-lysine (FL), glucosepane and methylglyoxal hydroimidazolone (MG-H1) emerges as extraordinarily strong predictors of existing and future microvascular disease progression risk despite adjustment for both past and prospective A1c levels. X(2) values are up to 25.1, p values generally less than 0.0001, and significance remains after adjustment for various factors such as A1c, former treatment group, log albumin excretion rate, abnormal autonomic nerve function and LDL levels at baseline. In contrast, subclinical cardiovascular progression is more weakly correlated with AGEs/glycemia with X(2) values < 5.0 and p values generally < 0.05 after all adjustments. Except for future carotid intima-media thickness, which correlates with total AGE burden (MG-H1, pentosidine, fluorophore LW-1 and decreased collagen solubility), adjusted FUR and Collagen Fluorescence (CLF) are the strongest markers for future coronary artery calcium deposition, while cardiac hypertrophy is associated with LW-1 and CLF adjusted for A1c. We conclude that a robust clinical skin biopsy AGE risk panel for microvascular disease should include at least FUR/FL, glucosepane and MG-H1, while a macrovascular disease risk panel should include at least FL/FUR, MG-H1, LW-1 and CLF.

  2. The pecking order of skin Advanced Glycation Endproducts (AGEs) as long-term markers of glycemic damage and risk factors for micro- and subclinical macrovascular disease progression in Type 1 diabetes.

    PubMed

    Monnier, Vincent M; Genuth, Saul; Sell, David R

    2016-08-01

    To date more than 20 glycation products were identified, of which ~15 in the insoluble human skin collagen fraction. The goal of this review is to streamline 30 years of research and ask a set of important questions: in Type 1 diabetes which glycation products correlate best with 1) past mean glycemia 2) reversibility with improved glycemic control, 2) cross-sectional severity of retinopathy, nephropathy and neuropathy and 3) the future long-term risk of progression of micro- and subclinical macrovascular disease. The trio of glycemia related glycation markers furosine (FUR)/fructose-lysine (FL), glucosepane and methylglyoxal hydroimidazolone (MG-H1) emerges as extraordinarily strong predictors of existing and future microvascular disease progression risk despite adjustment for both past and prospective A1c levels. X(2) values are up to 25.1, p values generally less than 0.0001, and significance remains after adjustment for various factors such as A1c, former treatment group, log albumin excretion rate, abnormal autonomic nerve function and LDL levels at baseline. In contrast, subclinical cardiovascular progression is more weakly correlated with AGEs/glycemia with X(2) values < 5.0 and p values generally < 0.05 after all adjustments. Except for future carotid intima-media thickness, which correlates with total AGE burden (MG-H1, pentosidine, fluorophore LW-1 and decreased collagen solubility), adjusted FUR and Collagen Fluorescence (CLF) are the strongest markers for future coronary artery calcium deposition, while cardiac hypertrophy is associated with LW-1 and CLF adjusted for A1c. We conclude that a robust clinical skin biopsy AGE risk panel for microvascular disease should include at least FUR/FL, glucosepane and MG-H1, while a macrovascular disease risk panel should include at least FL/FUR, MG-H1, LW-1 and CLF. PMID:27342131

  3. Receptor for Advanced Glycation End Products (RAGE) in Type 1 Diabetes Pathogenesis.

    PubMed

    Leung, Sherman S; Forbes, Josephine M; Borg, Danielle J

    2016-10-01

    The receptor for advanced glycation end products (RAGE) is a novel protein increasingly studied in the pathogenesis of type 1 diabetes (T1D). RAGE is expressed by several immune cell types, including T cells, antigen-presenting cells, endothelial cells, and the endocrine cells of the pancreatic islets. RAGE binds various ligands including advanced glycation end products (AGEs), high-mobility group box protein 1 (HMGB1), S100 proteins, β-amyloid, β-sheet fibrils, and lipopolysaccharide. AGEs are a particularly interesting ligand because their exogenous introduction into the body can be accelerated by the consumption of AGE-rich processed foods. This review will detail RAGE isoforms and its ligands and discuss how RAGE binding on the aforementioned cells could be linked to T1D pathogenesis. PMID:27612847

  4. Treatment of diabetic retinopathy: Recent advances and unresolved challenges

    PubMed Central

    Stewart, Michael W

    2016-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor (VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema (DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation (PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies.

  5. Treatment of diabetic retinopathy: Recent advances and unresolved challenges.

    PubMed

    Stewart, Michael W

    2016-08-25

    Diabetic retinopathy (DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor (VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema (DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation (PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies. PMID:27625747

  6. Treatment of diabetic retinopathy: Recent advances and unresolved challenges

    PubMed Central

    Stewart, Michael W

    2016-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor (VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema (DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation (PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies. PMID:27625747

  7. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

    PubMed Central

    Li, D.X.; Deng, T.Z.; Lv, J.; Ke, J.

    2014-01-01

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction. PMID:25387669

  8. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts.

    PubMed

    Li, D X; Deng, T Z; Lv, J; Ke, J

    2014-12-01

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80 ± 5.50%, P<0.01) and increased apoptosis (11.31 ± 1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

  9. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts.

    PubMed

    Li, D X; Deng, T Z; Lv, J; Ke, J

    2014-09-19

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

  10. Male biological clock: a critical analysis of advanced paternal age

    PubMed Central

    Ramasamy, Ranjith; Chiba, Koji; Butler, Peter; Lamb, Dolores J.

    2016-01-01

    Extensive research defines the impact of advanced maternal age on couples’ fecundity and reproductive outcomes, but significantly less research has been focused on understanding the impact of advanced paternal age. Yet it is increasingly common for couples at advanced ages to conceive children. Limited research suggests that the importance of paternal age is significantly less than that of maternal age, but advanced age of the father is implicated in a variety of conditions affecting the offspring. This review examines three aspects of advanced paternal age: the potential problems with conception and pregnancy that couples with advanced paternal age may encounter, the concept of discussing a limit to paternal age in a clinical setting, and the risks of diseases associated with advanced paternal age. As paternal age increases, it presents no absolute barrier to conception, but it does present greater risks and complications. The current body of knowledge does not justify dissuading older men from trying to initiate a pregnancy, but the medical community must do a better job of communicating to couples the current understanding of the risks of conception with advanced paternal age. PMID:25881878

  11. The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases.

    PubMed

    Maessen, Dionne E M; Stehouwer, Coen D A; Schalkwijk, Casper G

    2015-06-01

    The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

  12. Effect of advanced glycation end product intake on inflammation and aging: a systematic review.

    PubMed

    Van Puyvelde, Katrien; Mets, Tony; Njemini, Rose; Beyer, Ingo; Bautmans, Ivan

    2014-10-01

    Aging is associated with a chronic low-grade inflammatory status that contributes to chronic diseases such as age-related muscle wasting, kidney disease, and diabetes mellitus. Since advanced glycation end products (AGEs) are known to be proinflammatory, this systematic review examined the relation between the dietary intake of AGEs and inflammatory processes. The PubMed and Web of Science databases were screened systematically. Seventeen relevant studies in humans or animals were included. The intervention studies in humans showed mainly a decrease in inflammation in subjects on a low-AGE diet, while an increase in inflammation in subjects on a high-AGE diet was less apparent. About half of the observational studies found a relationship between inflammatory processes and AGEs in food. When the results are considered together, the dietary intake of AGEs appears to be related to inflammatory status and the level of circulating AGEs. Moreover, limiting AGE intake may lead to a decrease in inflammation and chronic diseases related to inflammatory status. Most of the trials were conducted in patients with chronic kidney disease or diabetes, and thus additional studies in healthy individuals are needed. Further investigation is needed to elucidate the effects of lifetime exposure of dietary AGEs on aging and health.

  13. Advances in management of type 1 diabetes mellitus

    PubMed Central

    Aathira, Ravindranath; Jain, Vandana

    2014-01-01

    Treatment of type 1 diabetes mellitus has always posed a challenge to balance hyperglycemia control with hypoglycemia episodes. The quest for newer therapies is continuing and this review attempts to outline the recent developments. The insulin molecule itself has got moulded into different analogues by minor changes in its structure to ensure well controlled delivery, stable half-lives and lesser side effects. Insulin delivery systems have also consistently undergone advances from subcutaneous injections to continuous infusion to trials of inhalational delivery. Continuous glucose monitoring systems are also becoming more accurate and user friendly. Smartphones have also made their entry into therapy of diabetes by integrating blood glucose levels and food intake with calculated adequate insulin required. Artificial pancreas has enabled to a certain extent to close the loop between blood glucose level and insulin delivery with devices armed with meal and exercise announcements, dual hormone delivery and pramlintide infusion. Islet, pancreas-kidney and stem cells transplants are also being attempted though complete success is still a far way off. Incorporating insulin gene and secretary apparatus is another ambitious leap to achieve insulin independence though the search for the ideal vector and target cell is still continuing. Finally to stand up to the statement, prevention is better than cure, immunological methods are being investigated to be used as vaccine to prevent the onset of diabetes mellitus. PMID:25317246

  14. Advances in management of type 1 diabetes mellitus.

    PubMed

    Aathira, Ravindranath; Jain, Vandana

    2014-10-15

    Treatment of type 1 diabetes mellitus has always posed a challenge to balance hyperglycemia control with hypoglycemia episodes. The quest for newer therapies is continuing and this review attempts to outline the recent developments. The insulin molecule itself has got moulded into different analogues by minor changes in its structure to ensure well controlled delivery, stable half-lives and lesser side effects. Insulin delivery systems have also consistently undergone advances from subcutaneous injections to continuous infusion to trials of inhalational delivery. Continuous glucose monitoring systems are also becoming more accurate and user friendly. Smartphones have also made their entry into therapy of diabetes by integrating blood glucose levels and food intake with calculated adequate insulin required. Artificial pancreas has enabled to a certain extent to close the loop between blood glucose level and insulin delivery with devices armed with meal and exercise announcements, dual hormone delivery and pramlintide infusion. Islet, pancreas-kidney and stem cells transplants are also being attempted though complete success is still a far way off. Incorporating insulin gene and secretary apparatus is another ambitious leap to achieve insulin independence though the search for the ideal vector and target cell is still continuing. Finally to stand up to the statement, prevention is better than cure, immunological methods are being investigated to be used as vaccine to prevent the onset of diabetes mellitus.

  15. Confocal Raman study of aging process in diabetes mellitus human voluntaries

    NASA Astrophysics Data System (ADS)

    Pereira, Liliane; Téllez Soto, Claudio Alberto; dos Santos, Laurita; Ali, Syed Mohammed; Fávero, Priscila Pereira; Martin, Airton A.

    2015-06-01

    Accumulation of AGEs [Advanced Glycation End - products] occurs slowly during the human aging process. However, its formation is accelerated in the presence of diabetes mellitus. In this paper, we perform a noninvasive analysis of glycation effect on human skin by in vivo confocal Raman spectroscopy. This technique uses a laser of 785 nm as excitation source and, by the inelastic scattering of light, it is possible to obtain information about the biochemical composition of the skin. Our aim in this work was to characterize the aging process resulting from the glycation process in a group of 10 Health Elderly Women (HEW) and 10 Diabetic Elderly Women (DEW). The Raman data were collected from the dermis at a depth of 70-130 microns. Through the theory of functional density (DFT) the bands positions of hydroxyproline, proline and AGEs (pentosidine and glucosepane) were calculated by using Gaussian 0.9 software. A molecular interpretation of changes in type I collagen was performed by the changes in the vibrational modes of the proline (P) and hydroxyproline (HP). The data analysis shows that the aging effects caused by glycation of proteins degrades type I collagen differently and leads to accelerated aging process.

  16. Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions

    PubMed Central

    2016-01-01

    Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD.

  17. Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions

    PubMed Central

    2016-01-01

    Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD. PMID:27695506

  18. Carboxymethyl lysine, an advanced glycation end-product, and incident diabetes: a case-cohort analysis of the ARIC Study

    PubMed Central

    Luft, V. C.; Duncan, B. B.; Schmidt, M. I.; Chambless, L. E.; Pankow, J. S.; Hoogeveen, R. C.; Couper, D. J.; Heiss, G.

    2016-01-01

    Aims To verify whether elevated fasting levels of circulating carboxymethyl lysine (CML), an advanced glycation end-product (AGE), predict the development of diabetes in middle-age adults. Methods Using a stratified case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 514 who did not over a median 9 years in the Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses were used to account for the design. Results In weighted analyses, correlation between CML levels and anthropometric, inflammatory or metabolic variables was minimal (Pearson correlations usually <0.10). CML, when modelled as a continuous variable and after adjustment for age, sex, race, centre, parental history of diabetes, body mass index, waist-to-hip ratio, NEFA, oxidized LDL-cholesterol, glomerular filtration rate, smoking, an inflammation score, adiponectin, leptin, insulin, and glucose levels, was associated with increased risk of diabetes (HR=1.35; 95% CI 1.09 – 1.67, for each 100 ng/mL CML increment). Baseline glucose level and race each modified the association (p<0.05 for interaction), which was present only among those with impaired fasting glucose (≥5.6 mmol/l, HR=1.61, 95%CI 1.26 – 2.05) and among whites (HR=1.50, 95%CI 1.13 – 1.99). Conclusions Elevated fasting CML, after adjustment for multiple risk factors for diabetes, predicts the development of incident diabetes, the association being present among those with impaired fasting glucose and in whites. These prospective findings suggest that AGE might play a role in the development of diabetes. PMID:26359784

  19. Research Advances in Aging 1984-1986.

    ERIC Educational Resources Information Center

    National Inst. on Aging (DHHS/NIH), Bethesda, MD.

    The National Institute on Aging (NIA) has, for the past several years, focused attention on a wide range of clinical problems associated with aging, including falls and gait disorders, bone fractures, urinary incontinence, and hypertension. Understanding the causes of and exploring possible treatments for Alzheimer's disease has been another of…

  20. Advances in the topical treatment of diabetic foot ulcers.

    PubMed

    Papanas, N; Eleftheriadou, I; Tentolouris, N; Maltezos, E

    2012-05-01

    The diabetic foot remains a major cause of morbidity worldwide. Even though considerable progress has been achieved over the past years, there is still an urgent need for improvement. While established therapeutic modalities (revascularization, casting and debridement) remain the mainstay of management, there is, therefore, continuous development of new treatment options. This review provides an outlook of advances in topical treatment, including bioengineered skin substitutes (such as Dermagraft, Apligraf, HYAFF, OASIS and Graftjacket), extracellular matrix proteins (such as Hyalofill and E-matrix), as well as miscellaneous further therapeutic adjuncts. Although promising, new therapies should not, for the time being, constitute the basis of management, since clinical experience has not yet confirmed their effectiveness in hard-to-heal diabetic foot ulcers. Furthermore, their cost-effectiveness merits further investigation. Instead, they should only be considered in combination with established treatments or be attempted when these have not been successful. Moreover, we should not be oblivious to the fact that established and emerging treatments need to be practised in the setting of multidisciplinary foot clinics to reduce the number of amputations.

  1. Advanced paternal age and reproductive outcome

    PubMed Central

    Wiener-Megnazi, Zofnat; Auslender, Ron; Dirnfeld, Martha

    2012-01-01

    Women have been increasingly delaying the start of motherhood in recent decades. The same trend is seen also for men. The influence of maternal age on fertility, chromosomal anomalies, pregnancy complications, and impaired perinatal and post-natal outcome of offspring, has been thoroughly investigated, and these aspects are clinically applied during fertility and pregestational counseling. Male aging and reproductive outcome has gained relatively less attention. The purpose of this review is to evaluate updated and relevant literature on the effect of paternal age on reproductive outcome. PMID:22157982

  2. Detection of advanced glycation end products (AGEs) on human skin by in vivo confocal Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Martin, A. A.; Pereira, L.; Ali, S. M.; Pizzol, C. D.; Tellez, C. A.; Favero, P. P.; Santos, L.; da Silva, V. V.; Praes, C. E. O.

    2016-03-01

    The aging process involves the reduction in the production of the major components of skin tissue. During intrinsic aging and photoaging processes, in dermis of human skin, fibroblasts become senescent and have decreased activity, which produce low levels of collagen. Moreover, there is accumulation of advanced glycation end products (AGEs). AGEs have incidence in the progression of age-related diseases, principally in diabetes mellitus and in Alzheimer's diseases. AGEs causes intracellular damage and/or apoptosis leading to an increase of the free radicals, generating a crosslink with skin proteins and oxidative stress. The aim of this study is to detect AGEs markers on human skin by in vivo Confocal Raman spectroscopy. Spectra were obtained by using a Rivers Diagnostic System, 785 nm laser excitation and a CCD detector from the skin surface down to 120 μm depth. We analyzed the confocal Raman spectra of the skin dermis of 30 women volunteers divided into 3 groups: 10 volunteers with diabetes mellitus type II, 65-80 years old (DEW); 10 young healthy women, 20-33 years old (HYW); and 10 elderly healthy women, 65-80 years old (HEW). Pentosidine and glucosepane were the principally identified AGEs in the hydroxyproline and proline Raman spectral region (1000-800 cm-1), in the 1.260-1.320 cm-1 region assignable to alpha-helical amide III modes, and in the Amide I region. Pentosidine and glucosepane calculated vibrational spectra were performed through Density Functional Theory using the B3LYP functional with 3-21G basis set. Difference between the Raman spectra of diabetic elderly women and healthy young women, and between healthy elderly women and healthy young women were also obtained with the purpose of identifying AGEs Raman bands markers. AGEs peaks and collagen changes have been identified and used to quantify the glycation process in human skin.

  3. Diabetes.

    PubMed

    2014-09-23

    Essential facts Type 1 and type 2 diabetes affect 3.2 million people in the UK. Diabetes is associated with serious complications, including heart disease and stroke, which can lead to disability and premature death. It is the leading cause of preventable sight loss in people of working age in the UK. A quarter of people with diabetes will have kidney disease at some point in their lives, and the condition increases the risk of amputation. Good diabetes management has been shown to reduce the incidence of these serious complications. PMID:25227362

  4. Advanced Glycation Endproducts and Bone Material Properties in Type 1 Diabetic Mice.

    PubMed

    Rubin, Mishaela R; Paschalis, Eleftherios P; Poundarik, Atharva; Sroga, Gyna E; McMahon, Donald J; Gamsjaeger, Sonja; Klaushofer, Klaus; Vashishth, Deepak

    2016-01-01

    Fractures, particularly at the lower extremities and hip, are a complication of diabetes. In both type 1 (T1D) and type 2 diabetes (T2D), fracture risk is disproportionately worse than that predicted from the measurement of bone mineral density. Although an explanation for this discrepancy is the presence of organic matrix abnormalities, it has not been fully elucidated how advanced glycation endproducts (AGEs) relate to bone deterioration at both the macroscopic and microscopic levels. We hypothesized that there would be a relationship between skeletal AGE levels (determined by Raman microspectroscopy at specific anatomical locations) and bone macroscopic and microscopic properties, as demonstrated by the biomechanical measures of crack growth and microindentation respectively. We found that in OVE26 mice, a transgenic model of severe early onset T1D, AGEs were increased by Raman (carboxymethyl-lysine [CML] wildtype (WT): 0.0143 ±0.0005 vs T1D: 0.0175 ±0.0002, p = 0.003) at the periosteal surface. These differences were associated with less tough bone in T1D by fracture mechanics (propagation toughness WT: 4.73 ± 0.32 vs T1D: 3.39 ± 0.24 NM/m1/2, p = 0.010) and by reference point indentation (indentation distance increase WT: 6.85 ± 0.44 vs T1D: 9.04 ± 0.77 μm; p = 0.043). Within T1D, higher AGEs by Raman correlated inversely with macroscopic bone toughness. These data add to the existing body of knowledge regarding AGEs and the relationship between skeletal AGEs with biomechanical indices. PMID:27140650

  5. Advanced Glycation Endproducts and Bone Material Properties in Type 1 Diabetic Mice

    PubMed Central

    Rubin, Mishaela R.; Paschalis, Eleftherios P.; Poundarik, Atharva; Sroga, Gyna E.; McMahon, Donald J.; Gamsjaeger, Sonja; Klaushofer, Klaus; Vashishth, Deepak

    2016-01-01

    Fractures, particularly at the lower extremities and hip, are a complication of diabetes. In both type 1 (T1D) and type 2 diabetes (T2D), fracture risk is disproportionately worse than that predicted from the measurement of bone mineral density. Although an explanation for this discrepancy is the presence of organic matrix abnormalities, it has not been fully elucidated how advanced glycation endproducts (AGEs) relate to bone deterioration at both the macroscopic and microscopic levels. We hypothesized that there would be a relationship between skeletal AGE levels (determined by Raman microspectroscopy at specific anatomical locations) and bone macroscopic and microscopic properties, as demonstrated by the biomechanical measures of crack growth and microindentation respectively. We found that in OVE26 mice, a transgenic model of severe early onset T1D, AGEs were increased by Raman (carboxymethyl-lysine [CML] wildtype (WT): 0.0143 ±0.0005 vs T1D: 0.0175 ±0.0002, p = 0.003) at the periosteal surface. These differences were associated with less tough bone in T1D by fracture mechanics (propagation toughness WT: 4.73 ± 0.32 vs T1D: 3.39 ± 0.24 NM/m1/2, p = 0.010) and by reference point indentation (indentation distance increase WT: 6.85 ± 0.44 vs T1D: 9.04 ± 0.77 μm; p = 0.043). Within T1D, higher AGEs by Raman correlated inversely with macroscopic bone toughness. These data add to the existing body of knowledge regarding AGEs and the relationship between skeletal AGEs with biomechanical indices. PMID:27140650

  6. Diabetes death rates among youths aged ≤ 19 years--United States, 1968-2009.

    PubMed

    2012-11-01

    Although diabetes mellitus most often is diagnosed in adulthood, it remains one of the most common serious chronic diseases of childhood. Youths with diabetes are at risk for diabetes-related mortality because of acute complications that can result from the condition, including diabetic ketoacidosis and hypoglycemia. In the United States in 2010, an estimated 215,000 persons aged ≤ 19 years had diagnosed diabetes. Medical care for diabetes has improved considerably in recent decades, leading to improved survival rates. However, recent trends in diabetes death rates among youths aged <10 years and 10-19 years in the United States have not been reported. To assess these trends, CDC analyzed data from the National Vital Statistics System for deaths in the United States with diabetes listed as the underlying cause during 1968-2009. This report highlights the results of that analysis, which found that diabetes-related mortality decreased 61%, from an annual rate of 2.69 per million for the period 1968-1969 to a rate of 1.05 per million in 2008-2009. The percentage decrease was greater among youths aged <10 years (78%) than among youths aged 10-19 years (52%). These findings demonstrate improvements in diabetes mortality among youths but also indicate a need for continued improvement in diabetes diagnosis and care. PMID:23114253

  7. Potential Dual Role of Eugenol in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights

    PubMed Central

    Singh, Priyanka; Jayaramaiah, Ramesha H.; Agawane, Sachin B.; Vannuruswamy, Garikapati; Korwar, Arvind M.; Anand, Atul; Dhaygude, Vitthal S.; Shaikh, Mahemud L.; Joshi, Rakesh S.; Boppana, Ramanamurthy; Kulkarni, Mahesh J.; Thulasiram, Hirekodathakallu V.; Giri, Ashok P.

    2016-01-01

    Medicinally important genus Ocimum harbors a vast pool of chemically diverse metabolites. Current study aims at identifying anti-diabetic candidate compounds from Ocimum species. Major metabolites in O. kilimandscharicum, O. tenuiflorum, O. gratissimum were purified, characterized and evaluated for anti-glycation activity. In vitro inhibition of advanced glycation end products (AGEs) by eugenol was found to be highest. Preliminary biophysical analysis and blind docking studies to understand eugenol-albumin interaction indicated eugenol to possess strong binding affinity for surface exposed lysines. However, binding of eugenol to bovine serum albumin (BSA) did not result in significant change in secondary structure of protein. In vivo diabetic mice model studies with eugenol showed reduction in blood glucose levels by 38% likely due to inhibition of α-glucosidase while insulin and glycated hemoglobin levels remain unchanged. Western blotting using anti-AGE antibody and mass spectrometry detected notably fewer AGE modified peptides upon eugenol treatment both in vivo and in vitro. Histopathological examination revealed comparatively lesser lesions in eugenol-treated mice. Thus, we propose eugenol has dual mode of action in combating diabetes; it lowers blood glucose by inhibiting α-glucosidase and prevents AGE formation by binding to ε-amine group on lysine, protecting it from glycation, offering potential use in diabetic management. PMID:26739611

  8. [Advances in the research of treating refractory diabetic wounds with stem cells].

    PubMed

    Gong, Jiahong; Lu, Shuliang

    2014-12-01

    With the growth of aging society, China has become the country of population with the highest incidence of diabetes in the world. Diabetes leads to pathological changes in vascular and nervous system, rendering the diabetic skin fragile and hard to heal if wounded; in the end most diabetic wounds tend to become chronic skin ulcers. The refractory diabetic wound is the result of various endogenous and exogenous factors. It is a quite complicated pathophysiologic event which lacks an effective and specific therapeutic method in clinic. The use of stem cells could be a new approach of treating diabetic chronic wounds since they have a potential ability of self-renovation and multi-directional differentiation which will promote angiogenesis and wound healing process, thus be beneficial in the care of ischemia diseases of the lower limb. This article reviews basic theory of treating diabetic wound and the changes in microenvironment, and prompts many successful cases in curing refractory diabetic wounds.

  9. Baking, ageing, diabetes: a short history of the Maillard reaction.

    PubMed

    Hellwig, Michael; Henle, Thomas

    2014-09-22

    The reaction of reducing carbohydrates with amino compounds described in 1912 by Louis-Camille Maillard is responsible for the aroma, taste, and appearance of thermally processed food. The discovery that non-enzymatic conversions also occur in organisms led to intensive investigation of the pathophysiological significance of the Maillard reaction in diabetes and ageing processes. Dietary Maillard products are discussed as "glycotoxins" and thus as a nutritional risk, but also increasingly with regard to positive effects in the human body. In this Review we give an overview of the most important discoveries in Maillard research since it was first described and show that the complex reaction, even after over one hundred years, has lost none of its interdisciplinary actuality. PMID:25044982

  10. Detection of galectin-3 and localization of advanced glycation end products (AGE) in human chronic skin wounds.

    PubMed

    Pepe, Daniel; Elliott, Christopher G; Forbes, Thomas L; Hamilton, Douglas W

    2014-02-01

    The matricellular protein galectin-3 (Gal-3) is upregulated in excisional skin repair in rats where it has been shown to modulate the inflammatory phase of repair. Recent research into kidney pathology has implicated Gal-3 as a receptor for advanced glycation end products (AGE), resulting in the binding and clearance of these molecules. AGEs are thought to contribute to defective skin repair in diabetic patients as well as a result of the normal aging process. However, the distribution and localization of Gal-3 and AGEs has never been performed in human chronic skin wound tissue. Using immunohistochemistry, the localization of Gal-3 and AGEs in tissue isolated from chronic wounds and non-involved skin from the same patient was investigated. Of the 16 patients from which tissue was isolated, 13 had type II diabetes, one had type I diabetes and 2 patients without diabetes were also examined. In non-involved dermis, Gal-3 was detected strongly in the epidermis and in the vasculature. However, at the wound edge and in the wound bed, the level of Gal-3 labelling was greatly reduced in both the epidermis and vasculature. Labelling of serial sections for Gal-3 and AGE demonstrated that where Gal-3 immunoreactivity is reduced in the epidermis and vasculature, there is a concomitant increase in the level of AGE staining. Interestingly, similar labelling patterns were evident in diabetic and non-diabetic patients. The results from our study demonstrate an inverse correlation between Gal-3 and AGEs localization, suggesting that Gal-3 may protect against accumulation of AGEs in wound healing.

  11. Diabetes type 2, hypertension and cognitive dysfunction in middle age women.

    PubMed

    Petrova, Marina; Prokopenko, Semen; Pronina, Elena; Mozheyko, Elena

    2010-12-15

    Type 2 diabetes mellitus and hypertension are two widely spread diseases among the adults that are known to be risk factors for vascular disease. They are highly related such that comorbidity is common. The purpose of the present study was to investigate the comorbid effects of type 2 diabetes and hypertension on cognitive decline. One hundred and thirteen patients with type 2 diabetes (women, age 56±7.4 years, diabetes duration 8±6.7 years, hypertension duration 13.4±7.7 years) were assessed for cognitive impairment (CI) in comparison with 27 diabetes patients without hypertension (women, age 53±7.45 years, diabetes duration 4.4±5.6 years), all non-demented at baseline. Patients were screened for cognitive dysfunction with the Mini Mental State Examination (MMSE), a clock-drawing test (CDT) and Frontal Assessment Battery (FAB). We assessed history of DM and hypertension by interview. 87% of women with diabetes and hypertension and 70% of normotensive diabetic patients had cognitive impairment (p=0.0282), of mild and subtle degree. The frequency of alterations in the FAB was higher in subjects with diabetes and hypertension (48%) compared to normotensive diabetic patients (26%) p=0.0402. Our results show that people with diabetes type 2 and hypertension demonstrate greater cognitive changes as compared to normotensive diabetic patients.

  12. Protein-bound advanced glycation endproducts (AGEs) as bioactive amino acid derivatives in foods.

    PubMed

    Henle, T

    2005-12-01

    The Maillard reaction or nonenzymatic browning is of outstanding importance for the formation of flavour and colour of heated foods. Corresponding reactions, also referred to as "glycation", are known from biological systems, where the formation of advanced glycation endproducts (AGEs) shall play an important pathophysiological role in diabetes and uremia. In this review, pathways leading to the formation of individual protein-bound lysine and arginine derivatives in foods are described and nutritional consequences resulting from this posttranslational modifications of food proteins are discussed. PMID:15997413

  13. The Role of AGE/RAGE Signaling in Diabetes-Mediated Vascular Calcification

    PubMed Central

    2016-01-01

    AGE/RAGE signaling has been a well-studied cascade in many different disease states, particularly diabetes. Due to the complex nature of the receptor and multiple intersecting pathways, the AGE/RAGE signaling mechanism is still not well understood. The purpose of this review is to highlight key areas of AGE/RAGE mediated vascular calcification as a complication of diabetes. AGE/RAGE signaling heavily influences both cellular and systemic responses to increase bone matrix proteins through PKC, p38 MAPK, fetuin-A, TGF-β, NFκB, and ERK1/2 signaling pathways in both hyperglycemic and calcification conditions. AGE/RAGE signaling has been shown to increase oxidative stress to promote diabetes-mediated vascular calcification through activation of Nox-1 and decreased expression of SOD-1. AGE/RAGE signaling in diabetes-mediated vascular calcification was also attributed to increased oxidative stress resulting in the phenotypic switch of VSMCs to osteoblast-like cells in AGEs-induced calcification. Researchers found that pharmacological agents and certain antioxidants decreased the level of calcium deposition in AGEs-induced diabetes-mediated vascular calcification. By understanding the role the AGE/RAGE signaling cascade plays diabetes-mediated vascular calcification will allow for pharmacological intervention to decrease the severity of this diabetic complication. PMID:27547766

  14. Recent advances in managing and understanding diabetic nephropathy

    PubMed Central

    Tang, Sydney C.W.; Chan, Gary C.W.; Lai, Kar Neng

    2016-01-01

    Diabetic nephropathy is the commonest cause of end-stage renal disease in most developed economies. Current standard of care for diabetic nephropathy embraces stringent blood pressure control via blockade of the renin-angiotensin-aldosterone system and glycemia control. Recent understanding of the pathophysiology of diabetic nephropathy has led to the development of novel therapeutic options. This review article focuses on available data from landmark studies on the main therapeutic approaches and highlights some novel management strategies. PMID:27303648

  15. Obesity and diabetes in an aging population: time to rethink definitions and management?

    PubMed

    Rothberg, Amy E; Halter, Jeffrey B

    2015-02-01

    Regardless of pathophysiology and diagnostic criteria, the population of older adults with diabetes is highly heterogeneous. As adults with type 2 diabetes age and develop multiple comorbid health conditions, they may experience many challenges to good diabetes care and self-management. Age of diagnosis and duration of diabetes largely determine the likelihood for comorbidity. Treating such a diverse elderly population may result in inadequate glycemic control either because of overtreatment, leading to hypoglycemia, or because of other complications and preexisting comorbidities. It is imperative that treatment decisions are based on patient preferences, unique and likely evolving health status, and longevity.

  16. Diabetes

    MedlinePlus

    ... version of this page please turn Javascript on. Diabetes What is Diabetes? Too Much Glucose in the Blood Diabetes means ... high, causing pre-diabetes or diabetes. Types of Diabetes There are three main kinds of diabetes: type ...

  17. Pentosidine: a molecular marker for the cumulative damage to proteins in diabetes, aging, and uremia.

    PubMed

    Sell, D R; Nagaraj, R H; Grandhee, S K; Odetti, P; Lapolla, A; Fogarty, J; Monnier, V M

    1991-12-01

    Collagen undergoes progressive browning with age and diabetes characterized by yellowing, fluorescence, and cross-linking. The present research was undertaken in order to investigate the nature of the collagen-linked fluorescence. Human collagen was exhaustively cleaved into peptides by enzymatic digestion. Upon purification, a highly fluorescent chromophore was identified and purified from old human collagen. Structure elucidation revealed the presence of an imidazo [4,5-b] pyridinium-type structure acting as a cross-link between arginine, lysine, and a pentose. This advanced glycosylation end-product and protein cross-link results from the reaction of pentoses with proteins and was named pentosidine. Further work indicated that long-term glycosylation of proteins with hexoses also leads to pentosidine formation through sugar fragmentation. The proposed mechanism of pentosidine formation involves the dehydration of the pentose-derived Amadori compound to form an intermediate which is attacked under base catalysis by the guanido group of arginine. The strict requirement for the Amadori rearrangement is uncertain. However, oxidation is definitely involved since pentosidine is not formed in the absence of oxygen. Five-carbon sugars contributing to pentosidine formation could be formed from larger sugars by oxidative fragmentation or from trioses, tetroses, and ketoses by condensation and/or reverse aldol reactions. Pentosidine increases exponentially in human skin at autopsy. Mean age-adjusted skin levels were significantly increased in subjects with uremia and especially in type 1 diabetics with uremia vs. controls. In skin biopsy, levels were significantly elevated in all diabetic (type 1) vs. control subjects. The highest degree of association was with the cumulative grade of diabetic complication (retinopathy, nephropathy, arterial stiffness, and joint stiffness). Pentosidine also forms in various proteins other than collagen, although to a much lesser extent. In

  18. The effects of advanced paternal age on fertility

    PubMed Central

    Kovac, Jason R; Addai, Josephine; Smith, Ryan P; Coward, Robert M; Lamb, Dolores J; Lipshultz, Larry I

    2013-01-01

    Modern societal pressures and expectations over the past several decades have resulted in the tendency for couples to delay conception. While women experience a notable decrease in oocyte production in their late thirties, the effect of age on spermatogenesis is less well described. While there are no known limits to the age at which men can father children, the effects of advanced paternal age are incompletely understood. This review summarizes the current state of knowledge regarding advanced paternal age and its implications on semen quality, reproductive success and offspring health. This review will serve as a guide to physicians in counseling men about the decision to delay paternity and the risks involved with conception later in life. PMID:23912310

  19. Persistence of the effect of birth size on dysglycaemia and type 2 diabetes in old age: AGES-Reykjavik Study.

    PubMed

    von Bonsdorff, Mikaela B; Muller, Majon; Aspelund, Thor; Garcia, Melissa; Eiriksdottir, Gudny; Rantanen, Taina; Gunnarsdottir, Ingibjörg; Birgisdottir, Bryndis Eva; Thorsdottir, Inga; Sigurdsson, Gunnar; Gudnason, Vilmundur; Launer, Lenore; Harris, Tamara B

    2013-08-01

    We studied the effect of birth size on glucose and insulin metabolism among old non-diabetic individuals. We also explored the combined effect of birth size and midlife body mass index (BMI) on type 2 diabetes in old age. Our study comprised 1,682 Icelanders whose birth records included anthropometrical data. The same individuals had participated in the prospective population-based Reykjavik Study, where BMI was assessed at a mean age of 47 years, and in the AGES-Reykjavik Study during 2002 to 2006, where fasting glucose, insulin and HbA1c were measured and homeostasis model assessment for the degree of insulin resistance (HOMA-IR) calculated at a mean age of 75.5 years. Type 2 diabetes was determined as having a history of diabetes, using glucose-modifying medication or fasting glucose of >7.0 mmol/l. Of the participants, 249 had prevalent type 2 diabetes in old age. Lower birth weight and body length were associated with higher fasting glucose, insulin, HOMA-IR and HbA1c among old non-diabetic individuals. Higher birth weight and ponderal index at birth decreased the risk for type 2 diabetes in old age, odds ratio (OR), 0.61 [95 % confidence interval (CI), 0.48-0.79] and 0.96 (95 % CI, 0.92-1.00), respectively. Compared with those with high birth weight and low BMI in midlife, the odds of diabetes was almost five-fold for individuals with low birth weight and high BMI (OR, 4.93; 95 % CI, 2.14-11.37). Excessive weight gain in adulthood might be particularly detrimental to the health of old individuals with low birth weight.

  20. Cardiac H2S Generation Is Reduced in Ageing Diabetic Mice.

    PubMed

    Jin, Sheng; Pu, Shi-Xin; Hou, Cui-Lan; Ma, Fen-Fen; Li, Na; Li, Xing-Hui; Tan, Bo; Tao, Bei-Bei; Wang, Ming-Jie; Zhu, Yi-Chun

    2015-01-01

    Aims. To examine whether hydrogen sulfide (H2S) generation changed in ageing diabetic mouse hearts. Results. Compared to mice that were fed tap water only, mice that were fed 30% fructose solution for 15 months exhibited typical characteristics of a severe diabetic phenotype with cardiac hypertrophy, fibrosis, and dysfunction. H2S levels in plasma, heart tissues, and urine were significantly reduced in these mice as compared to those in controls. The expression of the H2S-generating enzymes, cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase, was significantly decreased in the hearts of fructose-fed mice, whereas cystathionine-β-synthase levels were significantly increased. Conclusion. Our results suggest that this ageing diabetic mouse model developed diabetic cardiomyopathy and that H2S levels were reduced in the diabetic heart due to alterations in three H2S-producing enzymes, which may be involved in the pathogenesis of diabetic cardiomyopathy. PMID:26078817

  1. Cardiac H2S Generation Is Reduced in Ageing Diabetic Mice

    PubMed Central

    Jin, Sheng; Pu, Shi-Xin; Hou, Cui-Lan; Ma, Fen-Fen; Li, Na; Li, Xing-Hui; Tan, Bo; Tao, Bei-Bei; Wang, Ming-Jie; Zhu, Yi-Chun

    2015-01-01

    Aims. To examine whether hydrogen sulfide (H2S) generation changed in ageing diabetic mouse hearts. Results. Compared to mice that were fed tap water only, mice that were fed 30% fructose solution for 15 months exhibited typical characteristics of a severe diabetic phenotype with cardiac hypertrophy, fibrosis, and dysfunction. H2S levels in plasma, heart tissues, and urine were significantly reduced in these mice as compared to those in controls. The expression of the H2S-generating enzymes, cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase, was significantly decreased in the hearts of fructose-fed mice, whereas cystathionine-β-synthase levels were significantly increased. Conclusion. Our results suggest that this ageing diabetic mouse model developed diabetic cardiomyopathy and that H2S levels were reduced in the diabetic heart due to alterations in three H2S-producing enzymes, which may be involved in the pathogenesis of diabetic cardiomyopathy. PMID:26078817

  2. Kinetics, role and therapeutic implications of endogenous soluble form of receptor for advanced glycation end products (sRAGE) in diabetes.

    PubMed

    Yamagishi, Sho-ichi; Matsui, Takanori; Nakamura, Kazuo

    2007-10-01

    Reducing sugars can react non-enzymatically with amino groups of protein to form Amadori products. These early glycation products undergo further complex reaction such as rearrangement, dehydration, and condensation to become irreversibly cross-linked, heterogeneous fluorescent derivatives, termed advanced glycation end products (AGEs). The formation and accumulation of AGEs have been known to progress at an accelerated rate in diabetes. There is a growing body of evidence that AGEs and their receptor (RAGE) axis is implicated in the pathogenesis of diabetic vascular complications. Indeed, the engagement of RAGE with AGEs is shown to elicit oxidative stress generation and subsequently evoke inflammatory responses in various types of cells, thus playing an important role in the development and progression of diabetic micro- and macroangiopathy. Moreover, administration of a recombinant soluble form of RAGE (sRAGE), has been shown to suppress the development of accelerated atherosclerosis in diabetic apolipoprotein E-null mice. These observations suggest that exogenously administered sRAGE may capture and eliminate circulating AGEs, thus protecting against the AGEs-elicited tissue damage by acting as a decoy receptor. Recently, endogenous sRAGE has been identified in humans. However, there is few comprehensive review about the regulation and role of endogenous sRAGE in diabetes. In the former part of this paper, we review the role of the AGE-RAGE system in the pathogenesis of diabetic vascular complications. Then we summarize in the latter part of this review the kinetics and pathophysiological role of endogenous sRAGE in diabetes. We also discuss the possibility that endogenous sRAGE may be a therapeutic target for the prevention of diabetic vascular complications. PMID:17979674

  3. The low-AGE content of low-fat vegan diets could benefit diabetics - though concurrent taurine supplementation may be needed to minimize endogenous AGE production.

    PubMed

    McCarty, Mark F

    2005-01-01

    Increased endogenous generation of advanced glycation endproducts (AGEs) contributes importantly to the vascular complications of diabetes, in part owing to activation of the pro-inflammatory RAGE receptor. However, AGE-altered oligopeptides with RAGE-activating potential can also be absorbed from the diet, and indeed make a significant contribution to the plasma and tissue pool of AGEs; this contribution is especially prominent when compromised renal function impairs renal clearance of AGEs. Perhaps surprisingly, foods rich in both protein and fat, and cooked at high heat, tend to be the richest dietary sources of AGEs, whereas low-fat carbohydrate-rich foods tend to be relatively low in AGEs. Conceivably, this reflects the fact that the so-called "AGEs" in the diet are generated primarily, not by glycation reactions, but by interactions between oxidized lipids and protein; such reactions are known to give rise to certain prominent AGEs, such as epsilonN-carboxymethyl-lysine and methylglyoxal. Although roasted nuts and fried or broiled tofu are relatively high in AGEs, low-fat plant-derived foods, including boiled or baked beans, typically are low in AGEs. Thus, a low-AGE content may contribute to the many benefits conferred to diabetics by a genuinely low-fat vegan diet. Nonetheless, the plasma AGE content of healthy vegetarians has been reported to be higher than that of omnivores - suggesting that something about vegetarian diets may promote endogenous AGE production. Some researchers have proposed that the relatively high-fructose content of vegetarian diets may explain this phenomenon, but there so far is no clinical evidence that normal intakes of fructose have an important impact on AGE production. An alternative or additional possibility is that the relatively poor taurine status of vegetarians up-regulates the physiological role of myeloperoxidase-derived oxidants in the generation of AGEs - in which case, taurine supplementation might be expected to

  4. The low-AGE content of low-fat vegan diets could benefit diabetics - though concurrent taurine supplementation may be needed to minimize endogenous AGE production.

    PubMed

    McCarty, Mark F

    2005-01-01

    Increased endogenous generation of advanced glycation endproducts (AGEs) contributes importantly to the vascular complications of diabetes, in part owing to activation of the pro-inflammatory RAGE receptor. However, AGE-altered oligopeptides with RAGE-activating potential can also be absorbed from the diet, and indeed make a significant contribution to the plasma and tissue pool of AGEs; this contribution is especially prominent when compromised renal function impairs renal clearance of AGEs. Perhaps surprisingly, foods rich in both protein and fat, and cooked at high heat, tend to be the richest dietary sources of AGEs, whereas low-fat carbohydrate-rich foods tend to be relatively low in AGEs. Conceivably, this reflects the fact that the so-called "AGEs" in the diet are generated primarily, not by glycation reactions, but by interactions between oxidized lipids and protein; such reactions are known to give rise to certain prominent AGEs, such as epsilonN-carboxymethyl-lysine and methylglyoxal. Although roasted nuts and fried or broiled tofu are relatively high in AGEs, low-fat plant-derived foods, including boiled or baked beans, typically are low in AGEs. Thus, a low-AGE content may contribute to the many benefits conferred to diabetics by a genuinely low-fat vegan diet. Nonetheless, the plasma AGE content of healthy vegetarians has been reported to be higher than that of omnivores - suggesting that something about vegetarian diets may promote endogenous AGE production. Some researchers have proposed that the relatively high-fructose content of vegetarian diets may explain this phenomenon, but there so far is no clinical evidence that normal intakes of fructose have an important impact on AGE production. An alternative or additional possibility is that the relatively poor taurine status of vegetarians up-regulates the physiological role of myeloperoxidase-derived oxidants in the generation of AGEs - in which case, taurine supplementation might be expected to

  5. Litsea japonica extract inhibits neuronal apoptosis and the accumulation of advanced glycation end products in the diabetic mouse retina

    PubMed Central

    KIM, JUNGHYUN; KIM, CHAN-SIK; LEE, YUN MI; SOHN, EUNJIN; JO, KYUHYUNG; KIM, JIN SOOK

    2015-01-01

    The retinal accumulation of advanced glycation end products (AGEs) is a condition, which is found in diabetic retinopathy. The purpose of the present study was to investigate the protective effect of Litsea japonica extract (LJE) and to elucidate its underlying protective mechanism in model diabetic db/db mice. Male, 7 -week-old db/db mice were treated with LJE (100 or 250 mg/kg body weight) once a day orally for 12 weeks. The expression levels of AGEs and their receptor (RAGE) were subsequently assessed by immunohistochemistry. An electrophoretic mobility shift assay and southwestern histochemistry were used to detect activated nuclear factor κB (NF-κB). The immunohistochemical analysis demonstrated that LJE significantly reduced the expression levels of the AGEs and RAGE in the neural retinas of the db/db mice. LJE markedly inhibited the apop-tosis of retinal ganglion cells. In addition, LJE suppressed the activation of NF-κB. These results suggested that LJE may be beneficial for the treatment of diabetes-induced retinal neurodegeneration, and the ability of LJE to attenuate retinal ganglion cell loss may be mediated by inhibition of the accumulation of AGEs. PMID:25815519

  6. Advanced glycation End-products (AGEs): an emerging concern for processed food industries.

    PubMed

    Sharma, Chetan; Kaur, Amarjeet; Thind, S S; Singh, Baljit; Raina, Shiveta

    2015-12-01

    The global food industry is expected to increase more than US $ 7 trillion by 2014. This rise in processed food sector shows that more and more people are diverging towards modern processed foods. As modern diets are largely heat processed, they are more prone to contain high levels of advanced glycation end products (AGEs). AGEs are a group of complex and heterogeneous compounds which are known as brown and fluorescent cross-linking substances such as pentosidine, non-fluorescent cross-linking products such as methylglyoxal-lysine dimers (MOLD), or non-fluorescent, non-cross linking adducts such as carboxymethyllysine (CML) and pyrraline (a pyrrole aldehyde). The chemistry of the AGEs formation, absorption and bioavailability and their patho-biochemistry particularly in relation to different complications like diabetes and ageing discussed. The concept of AGEs receptor - RAGE is mentioned. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Different methods of detection and quantification along with types of agents used for the treatment of AGEs are reviewed. Generally, ELISA or LC-MS methods are used for analysis of foods and body fluids, however lack of universally established method highlighted. The inhibitory effect of bioactive components on AGEs by trapping variety of chemical moieties discussed. The emerging evidence about the adverse effects of AGEs makes it necessary to investigate the different therapies to inhibit AGEs.

  7. An Emerging Role of Glucagon-Like Peptide-1 in Preventing Advanced-Glycation-End-Product-Mediated Damages in Diabetes

    PubMed Central

    Puddu, Alessandra; Mach, François; Nencioni, Alessio; Viviani, Giorgio Luciano; Montecucco, Fabrizio

    2013-01-01

    Glucagon-like peptide-1 (GLP-1) is a gut hormone produced in the intestinal epithelial endocrine L cells by differential processing of the proglucagon gene. Released in response to the nutrient ingestion, GLP-1 plays an important role in maintaining glucose homeostasis. GLP-1 has been shown to regulate blood glucose levels by stimulating glucose-dependent insulin secretion and inhibiting glucagon secretion, gastric emptying, and food intake. These antidiabetic activities highlight GLP-1 as a potential therapeutic molecule in the clinical management of type 2 diabetes, (a disease characterized by progressive decline of beta-cell function and mass, increased insulin resistance, and final hyperglycemia). Since chronic hyperglycemia contributed to the acceleration of the formation of Advanced Glycation End-Products (AGEs, a heterogeneous group of compounds derived from the nonenzymatic reaction of reducing sugars with free amino groups of proteins implicated in vascular diabetic complications), the administration of GLP-1 might directly counteract diabetes pathophysiological processes (such as pancreatic β-cell dysfunction). This paper outlines evidence on the protective role of GLP-1 in preventing the deleterious effects mediated by AGEs in type 2 diabetes. PMID:23365488

  8. Dysfunctional protection against advanced glycation due to thiamine metabolism abnormalities in gestational diabetes.

    PubMed

    Bartáková, Vendula; Pleskačová, Anna; Kuricová, Katarína; Pácal, Lukáš; Dvořáková, Veronika; Bělobrádková, Jana; Tomandlová, Marie; Tomandl, Josef; Kaňková, Kateřina

    2016-08-01

    While the pathogenic role of dicarbonyl stress and accelerated formation of advanced glycation end products (AGEs) to glucose intolerance and to the development of diabetic complications is well established, little is known about these processes in gestational diabetes mellitus (GDM), a condition pathogenically quite similar to type 2 diabetes. The aims of the present study were (i) to determine plasma thiamine and erythrocyte thiamine diphosphate (TDP) and transketolase (TKT) activity in pregnant women with and without GDM, (ii) to assess relationships between thiamine metabolism parameters and selected clinical, biochemical and anthropometric characteristics and, finally, (iii) to analyse relationship between variability in the genes involved in the regulation of transmembrane thiamine transport (i.e. SLC19A2 and SLC19A3) and relevant parameters of thiamine metabolism. We found significantly lower plasma BMI adjusted thiamine in women with GDM (P = 0.002, Mann-Whitney) while levels of erythrocyte TDP (an active TKT cofactor) in mid-trimester were significantly higher in GDM compared to controls (P = 0.04, Mann-Whitney). However, mid-gestational TKT activity - reflecting pentose phosphate pathway activity - did not differ between the two groups (P > 0.05, Mann-Whitney). Furthermore, we ascertained significant associations of postpartum TKT activity with SNPs SLC19A2 rs6656822 and SLC19A3 rs7567984 (P = 0.03 and P = 0.007, resp., Kruskal-Wallis). Our findings of increased thiamine delivery to the cells without concomitant increase of TKT activity in women with GDM therefore indicate possible pathogenic role of thiamine mishandling in GDM. Further studies are needed to determine its contribution to maternal and/or neonatal morbidity.

  9. Reproduction at an advanced maternal age and maternal health.

    PubMed

    Sauer, Mark V

    2015-05-01

    Advanced age is a risk factor for female infertility, pregnancy loss, fetal anomalies, stillbirth, and obstetric complications. These concerns are based on centuries-old observations, yet women are delaying childbearing to pursue educational and career goals in greater numbers than ever before. As a result, reproductive medicine specialists are treating more patients with age-related infertility and recurrent pregnancy loss, while obstetricians are faced with managing pregnancies often complicated by both age and comorbidities. The media portrayal of a youthful but older woman, able to schedule her reproductive needs and balance family and job, has fueled the myth that "you can have it all," rarely characterizing the perils inherent to advanced-age reproduction. Reproductive medicine specialists and obstetrician/gynecologists should promote more realistic views of the evidence-based realities of advanced maternal age pregnancy, including its high-risk nature and often compromised outcomes. Doctors should also actively educate both patients and the public that there is a real danger of childlessness if individuals choose to delay reproduction.

  10. Recent Advances in Diagnostic Strategies for Diabetic Peripheral Neuropathy

    PubMed Central

    2016-01-01

    Diabetes is an increasing epidemic in Korea, and associated diabetic peripheral neuropathy (DPN) is its most common and disabling complication. DPN has an insidious onset and heterogeneous clinical manifestations, making it difficult to detect high-risk patients of DPN. Early diagnosis is recommended and is the key factor for a better prognosis and preventing diabetic foot ulcers, amputation, or disability. However, diagnostic tests for DPN are not clearly established because of the various pathophysiology developing from the nerve injury to clinical manifestations, differences in mechanisms according to the type of diabetes, comorbidities, and the unclear natural history of DPN. Therefore, DPN remains a challenge for physicians to screen, diagnose, follow up, and evaluate for treatment response. In this review, diagnosing DPN using various methods to assess clinical symptoms and/or signs, sensorineural impairment, and nerve conduction studies will be discussed. Clinicians should rely on established modalities and utilize current available testing as complementary to specific clinical situations. PMID:27246283

  11. Recent advances in exploring the genetic susceptibility to diabetic neuropathy.

    PubMed

    Politi, Cristina; Ciccacci, Cinzia; D'Amato, Cinzia; Novelli, Giuseppe; Borgiani, Paola; Spallone, Vincenza

    2016-10-01

    Diabetic polyneuropathy and cardiovascular autonomic neuropathy are common and disabling complications of diabetes. Although glycaemic control and cardiovascular risk factors are major contributory elements in its development, diabetic neuropathy recognizes a multifactorial influence and a multiplicity of pathogenetic mechanisms. Thus genetic and environmental factors may contribute to its susceptibility, each with a modest contribution, by targeting various metabolic and microvascular pathways whose alterations intervene in diabetic neuropathy pathogenesis. This review is aimed at describing major data from the available literature regarding genetic susceptibility to diabetic neuropathies. It provides an overview of the genes reported as associated with the development or progression of these complications, i.e. ACE, MTHFR, GST, GLO1, APOE, TCF7L2, VEGF, IL-4, GPX1, eNOS, ADRA2B, GFRA2, MIR146A, MIR128A. The identification of genetic susceptibility can help in both expanding the comprehension of the pathogenetic mechanisms of diabetic nerve damage and identifying biomarkers of risk prediction and response to therapeutic intervention.

  12. Skin autofluorescence relates to soluble receptor for advanced glycation end-products and albuminuria in diabetes mellitus.

    PubMed

    Skrha, J; Soupal, J; Loni Ekali, G; Prázný, M; Kalousová, M; Kvasnička, J; Landová, L; Zima, T; Skrha, J

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P < 0.0001). Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r = 0.37, P < 0.02 and r = 0.60, P < 0.0001), but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R (2) = 0.38). Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established.

  13. Skin autofluorescence relates to soluble receptor for advanced glycation end-products and albuminuria in diabetes mellitus.

    PubMed

    Skrha, J; Soupal, J; Loni Ekali, G; Prázný, M; Kalousová, M; Kvasnička, J; Landová, L; Zima, T; Skrha, J

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P < 0.0001). Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r = 0.37, P < 0.02 and r = 0.60, P < 0.0001), but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R (2) = 0.38). Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established. PMID:23671885

  14. Infection susceptibility and immune senescence with advancing age replicated in accelerated aging Lmna(Dhe) mice.

    PubMed

    Xin, Lijun; Jiang, Tony T; Kinder, Jeremy M; Ertelt, James M; Way, Sing Sing

    2015-12-01

    Aging confers increased susceptibility to common pathogens including influenza A virus. Despite shared vulnerability to infection with advancing age in humans and rodents, the relatively long time required for immune senescence to take hold practically restricts the use of naturally aged mice to investigate aging-induced immunological shifts. Here, we show accelerated aging Lmna(Dhe) mice with spontaneous mutation in the nuclear scaffolding protein, lamin A, replicate infection susceptibility, and substantial immune cell shifts that occur with advancing age. Naturally aged (≥ 20 month) and 2- to 3-month-old Lmna(Dhe) mice share near identically increased influenza A susceptibility compared with age-matched Lmna(WT) control mice. Increased mortality and higher viral burden after influenza infection in Lmna(Dhe) mice parallel reduced accumulation of lung alveolar macrophage cells, systemic expansion of immune suppressive Foxp3⁺ regulatory T cells, and skewed immune dominance among viral-specific CD8⁺T cells similar to the immunological phenotype of naturally aged mice. Thus, aging-induced infection susceptibility and immune senescence are replicated in accelerated aging Lmna(Dhe) mice. PMID:26248606

  15. [Advances in research of the mechanism of "covert disorder" in diabetic skin].

    PubMed

    Ge, Xiao-jing; Jiang, Yu-zhi; Zhang, Hong-wei

    2012-02-01

    The diabetic ulceration is not uncommon, and becomes refractory, as the skin in a diabetic patient is relatively thin as well as hypoesthetic and less sensitive to temperature. As there are already preexisting histological and cellular derangement in the skin, healing of the skin injury is difficult, thus resulting in an intractable ulceration. When diabetes is not controlled, the skin contents of sugar and advanced glycation end product accumulate, invoking cellular deformation and accumulation of matrix metalloproteinases (MMP), resulting in an imbalance between MMP and its inhibitors, malfunction of growth factors, and inflammatory reaction. These processes lead to obvious skin thinning, denaturation of connective tissues, thickening of vascular basal membrane, and neuropathy, etc. These pathological alterations could be recognized as "covert disorder" of skin in diabetic patients and may be underlying disorders in producing indolent diabetic ulcers.

  16. [Age-related features of immunocompetent cells of human placenta associated with diabetes mellitus].

    PubMed

    Durnova, A O; Poliakova, V O; Pal'chenko, N A

    2010-01-01

    The immune-competent cells of placenta play the important role in protection of developing fetus against infectious agents; but their dysfunction can lead to development of placental insufficiency that affects health both fetus and mother. The aim of this study was the comparative analysis of presence of immune competent cells in villous chorion of mature placenta, taken from women with diabetes of different age groups. In our study we found three subpopulations of immune cells in villous chorion of mature placenta: natural killer cells (NK), B-lymphocytes and macrophages. Prevailing subpopulation are macrophages, they are detected 1,8 times more often than B-lymphocytes, and 2,3 times more often than NK. The quantity of immune competent cells in groups with diabetes of various types is different. Thus, the greatest number of macrophages was detected in group with diabetes type II of middle age (29-35 years)-- 4.62 +/- 0.93%, B-lymphocytes in group of women with diabetes type I of younger age (18-28 years)--2.50 +/- 0.30%, NK-cells in group with diabetes type I of younger age--1.98 +/- 0,42%. Analysis of received data showed the differences in expression of markers of immune cells in women of different age groups, which brings about the conclusion of various reactance of immune system of women with diabetes depending on age. PMID:21033374

  17. [Melatonin secretion in women of advanced reproductive age].

    PubMed

    Ermolenko, K S; Rapoport, S I; Solov'eva, A V

    2013-01-01

    The patient's age is a key factor determining success of in vitro fertilization. The ovarian reserve and oocyte quality are known to decrease with age. Much attention has been given recently to the role of epiphysis and its hormone, melatonin, in synchronization of daily and seasonal biorhythms in anti-stress protection and neuroregulation of reproductive processes. The aim of our work was to study melatonin levels in infertile women of reproductive age. We also measured sex hormones, anti-Mullerian hormone, FSH, and LH in blood and melatonin sulfate in urine at 8 points (RIA). Women of advanced reproductive age showed markedly reduced melatonin secretion due to functional disorders in the hypothalamic-pituitary-gonadal axis. Results of the study suggest the necessity of prescription of exogenous melatonin to the patients included in assisted reproduction programs for the improvement of their efficacy.

  18. Age and Sex Influence Cystatin C in Adolescents With and Without Type 1 Diabetes

    PubMed Central

    Maahs, David M.; Prentice, Nicole; McFann, Kim; Snell-Bergeon, Janet K.; Jalal, Diana; Bishop, Franziska K.; Aragon, Brittany; Wadwa, R. Paul

    2011-01-01

    OBJECTIVE To compare serum cystatin C levels, a novel biomarker of renal function, in adolescents with and without type 1 diabetes and to determine what factors affect cystatin C levels. RESEARCH DESIGN AND METHODS Cystatin C was measured in youth 12–19 years of age with (n = 259, diabetes duration 9 ± 3 years, HbA1c 8.9 ± 1.6%) and without diabetes (n = 78). Data were compared by diabetes status, and linear regression was used to determine factors affecting cystatin C. RESULTS Cystatin C (0.698 ± 0.083 vs. 0.688 ± 0.127 mg/L, P = 0.40) was similar by diabetes status. In multiple linear regression, cystatin C was associated with age and serum creatinine in nondiabetic subjects and sex, age, and serum creatinine in subjects with diabetes (P < 0.05). CONCLUSIONS These data suggest sex differences and age-related changes in cystatin C in adolescents with type 1 diabetes. An understanding of these changes is needed to determine the potential role of cystatin C as a marker of renal function in this population. PMID:21926294

  19. Impact of Diabetes and Hyperglycemia on Survival in Advanced Breast Cancer Patients

    PubMed Central

    Villarreal-Garza, Cynthia; Shaw-Dulin, Robin; Lara-Medina, Fernando; Bacon, Ludwing; Rivera, Daniel; Urzua, Lorena; Aguila, Christian; Ramirez-Morales, Rebeca; Santamaria, Julieta; Bargallo, Enrique; Mohar, Alejandro; Herrera, Luis A.

    2012-01-01

    Purpose. We examined the impact of diabetes and hyperglycemia on cancer-specific survival of patients with metastatic or recurrent breast cancer (BC). Methods. We performed a retrospective analysis of 265 patients with advanced BC receiving palliative chemotherapy. BC-specific mortality was compared for diabetic and nondiabetic patients as well as for patients that presented hyperglycemia during treatment. Results. No difference was observed between the diabetic and nondiabetic patients in terms of overall survival (OS). A difference in OS was observed between nondiabetic patients and diabetic patients who had hyperglycemia. The OS was greater in diabetic patients with proper metabolic control than diabetic patients with hyperglycemia. The risk of death was higher in patients with mean glucose levels >130 mg/dL during treatment. Several factors were associated with poor OS: tumor stage, hormone-receptor-negative tumors, HER2 negative disease, multiple metastatic sites, presence of visceral metastases, and mean glucose >130 mg/dL. Conclusion. Elevated glucose levels are associated with a poor outcome in diabetic and nondiabetic patients in contrast to patients with normoglycemic levels, conferring an elevated risk of death. According to these results, clinicians should monitor glucose levels during treatment for advanced breast cancer disease and take action to maintain normal glucose levels. PMID:22919369

  20. Advanced glycation end products (AGEs) promote melanogenesis through receptor for AGEs

    PubMed Central

    Lee, Eun Jung; Kim, Ji Young; Oh, Sang Ho

    2016-01-01

    Accumulation of advanced glycation end products (AGEs) is linked with development or aggravation of many degenerative processes or disorders, including aging and atherosclerosis. AGEs production in skin cells is known to promote stiffness and loss of elasticity through their buildup in connective tissue. However, the impact of AGEs has yet to be fully explored in melanocytes. In this study, we confirmed the existence of receptor for AGE (RAGE) in melanocytes in western blot and immunofluorescence along with increased melanin production in ex vivo skin organ culture and in vitro melanocyte culture following AGEs treatment. Cyclic AMP response element-binding protein (CREB) and extracellular signal-regulated kinases (ERK) 1/2 are considered as key regulatory proteins in AGEs-induced melanogenesis. In addition, blockage experiment using anti-RAGE blocking antibody has indicated that RAGE plays a pivotal role in AGE-mediated melanogenesis. Therefore, it is apparent that AGEs, known markers of aging, promote melanogenesis via RAGE. In addition, AGEs could be implicated in pigmentation associated with photoaging according to the results of increased secretion of AGEs from keratinocytes following UV irradiation. AGE-mediated melanogenesis may thus hold promise as a novel mean of altering skin pigmentation. PMID:27293210

  1. Advanced glycation end products (AGEs) promote melanogenesis through receptor for AGEs.

    PubMed

    Lee, Eun Jung; Kim, Ji Young; Oh, Sang Ho

    2016-01-01

    Accumulation of advanced glycation end products (AGEs) is linked with development or aggravation of many degenerative processes or disorders, including aging and atherosclerosis. AGEs production in skin cells is known to promote stiffness and loss of elasticity through their buildup in connective tissue. However, the impact of AGEs has yet to be fully explored in melanocytes. In this study, we confirmed the existence of receptor for AGE (RAGE) in melanocytes in western blot and immunofluorescence along with increased melanin production in ex vivo skin organ culture and in vitro melanocyte culture following AGEs treatment. Cyclic AMP response element-binding protein (CREB) and extracellular signal-regulated kinases (ERK) 1/2 are considered as key regulatory proteins in AGEs-induced melanogenesis. In addition, blockage experiment using anti-RAGE blocking antibody has indicated that RAGE plays a pivotal role in AGE-mediated melanogenesis. Therefore, it is apparent that AGEs, known markers of aging, promote melanogenesis via RAGE. In addition, AGEs could be implicated in pigmentation associated with photoaging according to the results of increased secretion of AGEs from keratinocytes following UV irradiation. AGE-mediated melanogenesis may thus hold promise as a novel mean of altering skin pigmentation. PMID:27293210

  2. Evaluation of autofluorescent property of hemoglobin-advanced glycation end product as a long-term glycemic index of diabetes.

    PubMed

    Gopalkrishnapillai, Bijukumar; Nadanathangam, Vigneshwaran; Karmakar, Nivedita; Anand, Sneh; Misra, Anoop

    2003-04-01

    Current methods for measuring long-term glycemia in patients with diabetes are HbA(1c) and advanced glycation end products (AGEs), which are estimated by phenyl boronate affinity chromatography and competitive enzyme-linked immunosorbent assay, respectively. In this study, we hypothesize that the intrinsic fluorescence property of hemoglobin-AGE (Hb-AGE) may be a simple, accurate, and therefore better index for long-term glycemic status due to its highly specific nature and longer half-life. To establish this contention, in vitro and in vivo experiments were carried out. The former was performed by incubating commercially available hemoglobin with 5 and 20 mmol/l glucose and the latter through experimentally induced (streptozotocin) diabetes in an animal model (male Wistar rats) to identify the new fluorophore formed due to the nonenzymatic glycosylation of hemoglobin. An adduct exhibiting fluorescence at 308/345 nm of excitation/emission wavelengths has been identified and its time-dependent formation established. Under in vitro conditions, the first appearance of the new fluorophore was noticed only after a period of 2 months, whereas under in vivo conditions, it increased significantly after 2 months of hyperglycemia. Consistent with the observations, studies on patients with type 2 diabetes demonstrated an elevated level of this new fluorescent adduct in patients with persisting high levels of plasma glucose for >2 months. Based on the results obtained, Hb-AGE appears to be an efficient fluorescence-based biosensing molecule for the long-term monitoring of glycemic control in diabetes.

  3. Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk

    PubMed Central

    Brand, Judith S.; van der Schouw, Yvonne T.; Onland-Moret, N. Charlotte; Sharp, Stephen J.; Ong, Ken K.; Khaw, Kay-Tee; Ardanaz, Eva; Amiano, Pilar; Boeing, Heiner; Chirlaque, Maria-Dolores; Clavel-Chapelon, Françoise; Crowe, Francesca L.; de Lauzon-Guillain, Blandine; Duell, Eric J.; Fagherazzi, Guy; Franks, Paul W.; Grioni, Sara; Groop, Leif C.; Kaaks, Rudolf; Key, Timothy J.; Nilsson, Peter M.; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sánchez, María-José; Slimani, Nadia; Teucher, Birgit; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L.; Feskens, Edith J.M.; Langenberg, Claudia; Forouhi, Nita G.; Riboli, Elio; Wareham, Nicholas J.

    2013-01-01

    OBJECTIVE Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk. RESEARCH DESIGN AND METHODS Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied. RESULTS Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04–1.69), 1.09 (0.90–1.31), 0.97 (0.86–1.10), and 0.85 (0.70–1.03) for women with menopause at ages <40, 40–44, 45–49, and ≥55 years, respectively, relative to those with menopause at age 50–54 years. The HR per SD younger age at menopause was 1.08 (1.02–1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [1.01–1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05). CONCLUSIONS Early menopause is associated with a greater risk of type 2 diabetes. PMID:23230098

  4. Neuropsychological Impairment in School-Aged Children Born to Mothers With Gestational Diabetes.

    PubMed

    Bolaños, Lourdes; Matute, Esmeralda; Ramírez-Dueñas, María de Lourdes; Zarabozo, Daniel

    2015-10-01

    The aim of this study was to determine whether school-aged children born to mothers with gestational diabetes show delays in their neuropsychological development. Several key neuropsychological characteristics of 32 children aged 7 to 9 years born to mothers with gestational diabetes were examined by comparing their performance on cognitive tasks to that of 28 children aged 8 to 10 years whose mothers had glucose levels within normal limits during pregnancy. The gestational diabetes group showed low performance on graphic, spatial, and bimanual skills and a higher presence of soft neurologic signs. Lower scores for general intellectual level and the working memory index were also evident. Our results suggest that gestational diabetes is associated with mild cognitive impairment. PMID:25814475

  5. Site-specific analysis of advanced glycation end products in plasma proteins of type 2 diabetes mellitus patients.

    PubMed

    Greifenhagen, Uta; Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

    2016-08-01

    Advanced glycation end products (AGEs) are posttranslational modifications formed non-enzymatically from the reaction of carbohydrates and their degradation products with proteins. Accumulation of AGEs is associated with the progression of severe diabetic complications, for example, and elevated tissue levels of AGEs might even predict these pathologies. As AGE formation is often site-specific, mapping of these modification sites may reveal more sensitive and specific markers than the global tissue level. Here, 42 AGE modifications were identified in a bottom-up proteomic approach by tandem mass spectrometry, which corresponded to 36 sites in 22 high to medium abundant proteins in individual plasma samples obtained from type 2 diabetes mellitus (T2DM) patients with long disease duration (>10 years). Major modifications were glarg (11 modification sites) and carboxymethylation (5) of arginine and formylation (8), acetylation (7), and carboxymethylation (7) of lysine residues. Relative quantification of these sites in plasma samples obtained from normoglycemic individuals (n = 47) and patients with T2DM being newly diagnosed (n = 47) or of medium (2-5 years, n = 20) and long disease duration (>10 years, n = 20) did not reveal any significant differences. PMID:27236317

  6. Physicochemical properties of the aging and diabetic sand rat intervertebral disc.

    PubMed

    Ziv, I; Moskowitz, R W; Kraise, I; Adler, J H; Maroudas, A

    1992-03-01

    Hydration, fixed charge density, (FCD) and hydration under various osmotic pressures were compared in young, old, and young diabetic sand rats. This rat is a desert animal that may develop diabetes when fed a regular diet; it is also known to have radiographic and histologic evidence of intervertebral disc (IVD) disease. Forty-five rats and 180 IVD were used in this study; they were divided into three equal groups: young healthy, old healthy, and young diabetics. IVD, cancellous bone, and muscle were sampled from distal lumbar spines. The young diabetic rats (YD) were considerably heavier than the age-matched controls, had higher insulin and glucose levels, and all YD had cataracts. The discs of the young diabetic animals demonstrated decreased hydration, FCD and ability to resist compression under osmotic pressures as compared with the young and healthy discs and were more similar to the discs from old rats. The IVD is the most affected musculoskeletal connective tissue in sand rats with aging and diabetes. The aged and diabetic discs in the sand rat demonstrated changes similar to human changes with regard to lower hydration, FCD, and ability to resist osmotic pressure. Therefore, the sand rat may be a suitable animal model for studying the pathogenesis of disc degeneration.

  7. Oxidative Stress in Aging: Advances in Proteomic Approaches

    PubMed Central

    Ortuño-Sahagún, Daniel; Pallàs, Mercè; Rojas-Mayorquín, Argelia E.

    2014-01-01

    Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual's Quality of Life (QOL). Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS]), which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8), naked mole-rat (Heterocephalus glaber), and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS) and oxidative stress in aging. PMID:24688629

  8. Oxidative stress in aging: advances in proteomic approaches.

    PubMed

    Ortuño-Sahagún, Daniel; Pallàs, Mercè; Rojas-Mayorquín, Argelia E

    2014-01-01

    Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual's Quality of Life (QOL). Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS]), which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8), naked mole-rat (Heterocephalus glaber), and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS) and oxidative stress in aging.

  9. Age and diabetes related changes of the retinal capillaries: An ultrastructural and immunohistochemical study.

    PubMed

    Bianchi, Enrica; Ripandelli, Guido; Taurone, Samanta; Feher, Janos; Plateroti, Rocco; Kovacs, Illes; Magliulo, Giuseppe; Orlando, Maria Patrizia; Micera, Alessandra; Battaglione, Ezio; Artico, Marco

    2016-03-01

    Normal human aging and diabetes are associated with a gradual decrease of cerebral flow in the brain with changes in vascular architecture. Thickening of the capillary basement membrane and microvascular fibrosis are evident in the central nervous system of elderly and diabetic patients. Current findings assign a primary role to endothelial dysfunction as a cause of basement membrane (BM) thickening, while retinal alterations are considered to be a secondary cause of either ischemia or exudation. The aim of this study was to reveal any initial retinal alterations and variations in the BM of retinal capillaries during diabetes and aging as compared to healthy controls. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in diabetic retina.Transmission electron microscopy (TEM) was performed on 46 enucleated human eyes with particular attention to alterations of the retinal capillary wall and Müller glial cells. Inflammatory cytokines expression in the retina was investigated by immunohistochemistry.Our electron microscopy findings demonstrated that thickening of the BM begins primarily at the level of the glial side of the retina during aging and diabetes. The Müller cells showed numerous cytoplasmic endosomes and highly electron-dense lysosomes which surrounded the retinal capillaries. Our study is the first to present morphological evidence that Müller cells start to deposit excessive BM material in retinal capillaries during aging and diabetes. Our results confirm the induction of pro-inflammatory cytokines TNF-α and IL-1β within the retina as a result of diabetes.These observations strongly suggest that inflammatory cytokines and changes in the metabolism of Müller glial cells rather than changes in of endothelial cells may play a primary role in the alteration of retinal capillaries BM during aging and diabetes. PMID:26604209

  10. [Recent advances in the treatment of type 1 diabetes mellitus].

    PubMed

    Schloot, N C; Roden, M; Bornstein, S R; Brendel, M D

    2011-02-01

    INTERVENTIONAL APPROACHES TO BETA CELL PRESERVATION: In a pilot study, initial attempts at primary prevention by preserving islet beta cells have been successful with highly hydrolyzed milk formula in children who are at high genetic risk of diabetes. Attempts at secondary prevention by intranasal application in children with a high-risk HLA genotype and positive islet autoantibodies have been disappointing. But in tertiary prevention anti-inflammatory, antigen-directed and T-cell targeted treatment has been partially successful in slowing down the destruction of beta cells. BIOLOGICAL BETA CELL SUBSTITUTION: Transplantation of a vascularised pancreas or islet cells results in disease regression and the prevention of secondary/tertiary complications of diabetes. A principal aim is the avoidance of frequent, severe hypoglycaemic episodes resulting from markedly reduced awareness of hypoglycaemia or its counter-regulation.

  11. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells.

    PubMed

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies. PMID:26907255

  12. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells

    PubMed Central

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies. PMID:26907255

  13. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells.

    PubMed

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.

  14. Diabetes and Pre-Diabetes among Persons Aged 35 to 60 Years in Eastern Uganda: Prevalence and Associated Factors

    PubMed Central

    Mayega, Roy William; Guwatudde, David; Makumbi, Fredrick; Nakwagala, Frederick Nelson; Peterson, Stefan; Tomson, Goran; Ostenson, Claes-Goran

    2013-01-01

    Background Our aim was to estimate the prevalence of abnormal glucose regulation (AGR) (i.e. diabetes and pre-diabetes) and its associated factors among people aged 35-60 years so as to clarify the relevance of targeted screening in rural Africa. Methods A population-based survey of 1,497 people (786 women and 711 men) aged 35-60 years was conducted in a predominantly rural Demographic Surveillance Site in eastern Uganda. Participants responded to a lifestyle questionnaire, following which their Body Mass Index (BMI) and Blood Pressure (BP) were measured. Fasting plasma glucose (FPG) was measured from capillary blood using On-Call® Plus (Acon) rapid glucose meters, following overnight fasting. AGR was defined as FPG ≥6.1mmol L-1 (World Health Organization (WHO) criteria or ≥5.6mmol L-1 (American Diabetes Association (ADA) criteria. Diabetes was defined as FPG >6.9mmol L-1, or being on diabetes treatment. Results The mean age of participants was 45 years for men and 44 for women. Prevalence of diabetes was 7.4% (95%CI 6.1-8.8), while prevalence of pre-diabetes was 8.6% (95%CI 7.3-10.2) using WHO criteria and 20.2% (95%CI 17.5-22.9) with ADA criteria. Using WHO cut-offs, the prevalence of AGR was 2 times higher among obese persons compared with normal BMI persons (Adjusted Prevalence Rate Ratio (APRR) 1.9, 95%CI 1.3-2.8). Occupation as a mechanic, achieving the WHO recommended physical activity threshold, and higher dietary diversity were associated with lower likelihood of AGR (APRR 0.6, 95%CI 0.4-0.9; APRR 0.6, 95%CI 0.4-0.8; APRR 0.5, 95%CI 0.3-0.9 respectively). The direct medical cost of detecting one person with AGR was two US dollars with ADA and three point seven dollars with WHO cut-offs. Conclusions There is a high prevalence of AGR among people aged 35-60 years in this setting. Screening for high risk persons and targeted health education to address obesity, insufficient physical activity and non-diverse diets are necessary. PMID:23967317

  15. Searching for the Kinkeepers: Historian Gender, Age, and Type 2 Diabetes Family History

    ERIC Educational Resources Information Center

    Giordimaina, Alicia M.; Sheldon, Jane P.; Kiedrowski, Lesli A.; Jayaratne, Toby Epstein

    2015-01-01

    Kinkeepers facilitate family communication and may be key to family medical history collection and dissemination. Middle-aged women are frequently kinkeepers. Using type 2 diabetes (T2DM) as a model, we explored whether the predicted gender and age effects of kinkeeping can be extended to family medical historians. Through a U.S. telephone survey,…

  16. When aging-onset diabetes is coming across with Alzheimer disease: comparable pathogenesis and therapy.

    PubMed

    Tang, Jun; Pei, Yijin; Zhou, Guangji

    2013-08-01

    Diabetes mellitus is a metabolic disorder that is characterized by high blood glucose because of the insulin-resistance and insulin-deficiency in Type 2, while the insulin deficiency due to destruction of islet cells in the pancreas in Type 1. The development of Type 2 diabetes is caused by a combination of lifestyle and genetic factors. Aging patients with diabetes are at increased risk of developing cognitive and memory dysfunctions, which is one of the significant symptoms of Alzheimer disease (AD). Also, over 2/3 of AD patients were clinically indentified with impairment of glucose. Cognitive dysfunction would be associated with poor self-care ability in diabetes patients. This review will briefly summarize the current knowledge of the pathogenesis of these two diseases and highlight similarities in their pathophysiologies. Furthermore, we will shortly discuss recent progress in the insulin-targeted strategy, aiming to explore the inner linkage between these two diseases in aging populations.

  17. Biphasic Decline of β-Cell Function with Age in Euglycemic Non-Obese Diabetic (NOD) Mice Parallels Diabetes Onset

    PubMed Central

    Cechin, Sirlene R.; Lopez-Ocejo, Omar; Karpinsky-Semper, Darla; Buchwald, Peter

    2015-01-01

    A gradual decline in insulin response is known to precede the onset of type 1 diabetes (T1D). To track age-related changes in the β-cell function of non-obese diabetic (NOD) mice, the most commonly used animal model for T1D, and to establish differences between those who do and do not become hyperglycemic, we performed a long-term longitudinal oral glucose tolerance test (OGTT) study (10–42 weeks) in combination with immunofluorescence imaging of islet morphology and cell proliferation. We observed a clear biphasic decline in insulin secretion (AUC0–30min) even in euglycemic animals. A first phase (10–28 weeks) consisted of a relatively rapid decline and paralleled diabetes development in the same cohort of animals. This was followed by a second phase (29–42 weeks) during which insulin secretion declined much slower while no additional animals became diabetic. Blood glucose profiles showed a corresponding, but less pronounced change: the area under the concentration curve (AUC0–150min) increased with age, and fit with a bilinear model indicated a rate-change in the trendline around 28 weeks. In control NOD scids, no such changes were observed. Islet morphology also changed with age as islets become surrounded by mononuclear infiltrates, and, in all mice, islets with immune cell infiltration around them showed increased β-cell proliferation. In conclusion, insulin secretion declines in a biphasic manner in all NOD mice. This trend, as well as increased β-cell proliferation, is present even in the NODs that never become diabetic, whereas, it is absent in control NOD scid mice. PMID:26099053

  18. Pathophysiology of diabetic erectile dysfunction: potential contribution of vasa nervorum and advanced glycation endproducts.

    PubMed

    Cellek, S; Cameron, N E; Cotter, M A; Muneer, A

    2013-01-01

    Erectile dysfunction (ED) due to diabetes mellitus remains difficult to treat medically despite advances in pharmacotherapeutic approaches in the field. This unmet need has resulted in a recent re-focus on the pathophysiology, in order to understand the cellular and molecular mechanisms leading to ED in diabetes. Diabetes-induced ED is often resistant to PDE5 inhibitor treatment, thus there is a need to discover targets that may lead to novel approaches for a successful treatment. The aim of this brief review is to update the reader in some of the latest development on that front, with a particular focus on the role of impaired neuronal blood flow and the formation of advanced glycation endproducts.

  19. Pathophysiology of diabetic erectile dysfunction: potential contribution of vasa nervorum and advanced glycation endproducts.

    PubMed

    Cellek, S; Cameron, N E; Cotter, M A; Muneer, A

    2013-01-01

    Erectile dysfunction (ED) due to diabetes mellitus remains difficult to treat medically despite advances in pharmacotherapeutic approaches in the field. This unmet need has resulted in a recent re-focus on the pathophysiology, in order to understand the cellular and molecular mechanisms leading to ED in diabetes. Diabetes-induced ED is often resistant to PDE5 inhibitor treatment, thus there is a need to discover targets that may lead to novel approaches for a successful treatment. The aim of this brief review is to update the reader in some of the latest development on that front, with a particular focus on the role of impaired neuronal blood flow and the formation of advanced glycation endproducts. PMID:22914567

  20. Soft-shelled turtle eggs inhibit the formation of AGEs in the serum and skin of diabetic rats

    PubMed Central

    Yamanaka, Mikihiro; Shirakawa, Jun-ichi; Ohno, Rei-ichi; Shinagawa, Masatoshi; Hatano, Kota; Sugawa, Hikari; Arakawa, Shoutaro; Furusawa, Chisato; Nagai, Mime; Nagai, Ryoji

    2016-01-01

    Although soft-shelled turtle eggs (STE) have been used as a folk medicine for revitalization and the prevention of lifestyle-related diseases, the scientific evidence to support the use of STE in this manner is scarce. To clarify the physiological evidence, STE was administered to diabetic rats and the inhibitory effects on the formation of advanced glycation end-products (AGEs), which are known to increase with the progression of lifestyle-related diseases, were examined. STE and citric acid were administered to diabetic rats for 3 months, and serum Nε-(carboxymethyl)lysine (CML) contents were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although the administration of STE did not affect the body weight, glycoalbumin or ketone body levels, it significantly reduced the serum level of CML. The accumulation of AGEs, which was measured by fluorescence intensity in the auricle skin and the lower gums, was also reduced by the administration of STE to a similar extent to that observed with citric acid. This report provides the first evidence that the oral administration of STE reduces the formation of AGEs, suggesting that one of the health effects of STE may be the inhibition of AGEs formation. PMID:27013779

  1. Soft-shelled turtle eggs inhibit the formation of AGEs in the serum and skin of diabetic rats.

    PubMed

    Yamanaka, Mikihiro; Shirakawa, Jun-Ichi; Ohno, Rei-Ichi; Shinagawa, Masatoshi; Hatano, Kota; Sugawa, Hikari; Arakawa, Shoutaro; Furusawa, Chisato; Nagai, Mime; Nagai, Ryoji

    2016-03-01

    Although soft-shelled turtle eggs (STE) have been used as a folk medicine for revitalization and the prevention of lifestyle-related diseases, the scientific evidence to support the use of STE in this manner is scarce. To clarify the physiological evidence, STE was administered to diabetic rats and the inhibitory effects on the formation of advanced glycation end-products (AGEs), which are known to increase with the progression of lifestyle-related diseases, were examined. STE and citric acid were administered to diabetic rats for 3 months, and serum N (ε)-(carboxymethyl)lysine (CML) contents were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although the administration of STE did not affect the body weight, glycoalbumin or ketone body levels, it significantly reduced the serum level of CML. The accumulation of AGEs, which was measured by fluorescence intensity in the auricle skin and the lower gums, was also reduced by the administration of STE to a similar extent to that observed with citric acid. This report provides the first evidence that the oral administration of STE reduces the formation of AGEs, suggesting that one of the health effects of STE may be the inhibition of AGEs formation. PMID:27013779

  2. Are We in the Same Risk of Diabetes Mellitus? Gender- and Age-Specific Epidemiology of Diabetes in 2001 to 2014 in the Korean Population

    PubMed Central

    Koo, Bo Kyung

    2016-01-01

    In the early 2000s, the prevalence of diabetes in adults aged ≥30 years in Korea was about 9% to 10%, and it remained stable. However, a nationwide survey showed that this prevalence increased over the past few years. After age-standardization using the Korean population of the year 2010, the prevalence of diabetes in adults aged ≥30 years was 10.0% to 10.8% between 2001 and 2012, which increased to 12.5% in 2013 and 11.6% in 2014. During that period, there have been changes in the gender- and age-specific prevalence of diabetes in Korean adults. The prevalence of diabetes in the elderly population increased significantly, while this prevalence in young adults, especially in young women, did not change significantly. The contribution of each diabetic risk factor, such as obesity, β-cell dysfunction, sarcopenia, and socioeconomic status, in developing diabetes has also changed during that period in each gender and age group. For young women, obesity was the most important risk factor; by contrast, for elderly diabetic patients, sarcopenia was more important than obesity as a risk factor. Considering the economic burden of diabetes and its associated comorbidities, a public health policy targeting the major risk factors in each population might be more effective in preventing diabetes. PMID:27273907

  3. Sexuality in advanced age in Jewish thought and law.

    PubMed

    David, Benjamin E; Weitzman, Gideon A

    2015-01-01

    Judaism has a positive attitude to sexual relations within a marriage, and views such sexual relations as important not only for procreation but also as part of the framework of marriage. This is true for any age group, and sexuality is seen as an essential element of marriage for couples of advanced age. In this article, the authors present the views of Jewish law and thought regarding sexuality among older couples. The authors illustrate this using 3 case studies of couples who sought guidance in the area of sexuality. In addition, this area of counseling benefits greatly from an ongoing relationship and dialogue between expert rabbis in the field and therapists treating older Orthodox Jewish patients for sexual dysfunction. The triad relationship of couple, therapist, and rabbi enhances the ability to treat and assist such couples to seek treatment and overcome their difficulties. PMID:24313599

  4. Coming of age: the artificial pancreas for type 1 diabetes.

    PubMed

    Thabit, Hood; Hovorka, Roman

    2016-09-01

    The artificial pancreas (closed-loop system) addresses the unmet clinical need for improved glucose control whilst reducing the burden of diabetes self-care in type 1 diabetes. Glucose-responsive insulin delivery above and below a preset insulin amount informed by sensor glucose readings differentiates closed-loop systems from conventional, threshold-suspend and predictive-suspend insulin pump therapy. Insulin requirements in type 1 diabetes can vary between one-third-threefold on a daily basis. Closed-loop systems accommodate these variations and mitigate the risk of hypoglycaemia associated with tight glucose control. In this review we focus on the progress being made in the development and evaluation of closed-loop systems in outpatient settings. Randomised transitional studies have shown feasibility and efficacy of closed-loop systems under supervision or remote monitoring. Closed-loop application during free-living, unsupervised conditions by children, adolescents and adults compared with sensor-augmented pumps have shown improved glucose outcomes, reduced hypoglycaemia and positive user acceptance. Innovative approaches to enhance closed-loop performance are discussed and we also present the outlook and strategies used to ease clinical adoption of closed-loop systems. PMID:27364997

  5. Cardiac and renal function are progressively impaired with aging in Zucker diabetic fatty type II diabetic rats.

    PubMed

    Baynes, John; Murray, David B

    2009-01-01

    This study investigated the temporal relationship between cardiomyopathy and renal pathology in the type II diabetic Zucker diabetic fatty (ZDF) rat. We hypothesized that changes in renal function will precede the development of cardiac dysfunction in the ZDF rat. Animals (10 weeks old) were divided into four experimental groups: Lean Control (fa/?) LC(n = 7), untreated ZDF rats (n = 7) sacrificed at 16 weeks of age, and LC (n = 7) untreated ZDF rats (n = 9) sacrificed at 36 weeks of age. LV structural/functional parameters were assessed via Millar conductance catheter. Renal function was evaluated via markers of proteinuria and evidence of hydronephrosis. LV mass was significantly less in the ZDF groups at both time points compared to age-matched LC. End diastolic volume was increased by 16% at 16 weeks and by 37% at 36 weeks of age (p < 0.05 vs. LC). End diastolic pressure and end systolic volume were significantly increased (42% and 27%respectively) at 36 weeks of age in the ZDF compared to LC. Kidney weights were significantly increased at both 16 and 36 week in ZDF animals (p < 0.05 vs. LC). Increased urinary albumin and decreased urinary creatinine were paralleled by a marked progression in the severity of hydronephrosis from 16 to 36 weeks of age in the ZDF group. In summary, there is evidence of progressive structural and functional changes in both the heart and kidney, starting as early as 16 weeks,without evidence that one pathology precedes or causes the other in the ZDF model of type II diabetes.

  6. Definition of advanced age in HIV infection: looking for an age cut-off.

    PubMed

    Blanco, José R; Jarrín, Inmaculada; Vallejo, Manuel; Berenguer, Juan; Solera, Carmen; Rubio, Rafael; Pulido, Federico; Asensi, Victor; del Amo, Julia; Moreno, Santiago

    2012-09-01

    The age of 50 has been considered as a cut-off to discriminate older subjects within HIV-infected people according to the Centers for Disease Control and Prevention (CDC). However, the International AIDS Society (IAS) mentions 60 years of age and the Department of Health and Human Services (DHHS) makes no consideration. We aimed to establish an age cut-off that could differentiate response to highly active antiretroviral therapy (HAART) and, therefore, help to define advanced age in HIV-infected patients. CoRIS is an open, prospective, multicenter cohort of HIV adults naive to HAART at entry (January 2004 to October 2009). Survival, immunological response (IR) (CD4 increase of more than 100 cell/ml), and virological response (VR) (HIV RNA less than 50 copies/ml) were compared among 5-year age intervals at start of HAART using Cox proportional hazards models, stratified by hospital and adjusted for potential confounders. Among 5514 patients, 2726 began HAART. During follow-up, 2164 (79.4%) patients experienced an IR, 1686 (61.8%) a VR, and 54 (1.9%) died. Compared with patients aged <25 years at start of HAART, those aged 50-54, 55-59, 60-64, 65-59, and 70 or older were 32% (aHR: 0.68, 95% CI: 0.52-0.87), 29% (aHR: 0.71, 95% CI: 0.53-0.96), 34% (aHR: 0.66, 95% CI: 0.46-0.95), 39% (aHR: 0.61, 95% CI: 0.37-1.00), and 43% (aHR: 0.57, 95% CI: 0.31-1.04) less likely to experience an IR. The VR was similar across all age groups. Finally, patients aged 50-59 showed a 3-fold increase (aHR: 3.58; 95% CI: 1.07-11.99) in their risk of death compared to those aged <30 years. In HIV infection, patients aged ≥50 years have a poorer immunological response to HAART and a poorer survival. This age could be used to define medically advanced age in HIV-infected people.

  7. Age and sex based genetic locus heterogeneity in type 1 diabetes

    PubMed Central

    Paterson, A.; Petronis, A.

    2000-01-01

    BACKGROUND—Two genome scans for susceptibility loci for type 1 diabetes using large collections of families have recently been reported. Apart from strong linkage in both studies of the HLA region on chromosome 6p, clear consistent evidence for linkage was not observed at any other loci. One possible explanation for this is a high degree of locus heterogeneity in type 1 diabetes, and we hypothesised that the sex of affected offspring, age of diagnosis, and parental origin of shared alleles may be the bases of heterogeneity at some loci.
METHODS—Using data from a genome wide linkage study of 356 affected sib pairs with type 1 diabetes, we performed linkage analyses using parental origin of shared alleles in subgroups based on (1) sex of affected sibs and (2) age of diagnosis.
RESULTS—Among the results obtained, we observed that evidence for linkage to IDDM4 on chromosome 11q13 occurred predominantly from opposite sex, rather than same sex sib pairs. At a locus on chromosome 4q, evidence for linkage was observed in sibs where one was diagnosed above the age of 10 years and the other diagnosed below 10 years of age.
CONCLUSIONS—We show that heterogeneity tests based on age of diagnosis, sex of affected subject, and parental origin of shared alleles may be helpful in reducing locus heterogeneity in type 1 diabetes. If repeated in other samples, these findings may assist in the mapping of susceptibility loci for type 1 diabetes. Similar analyses can be recommended in other complex diseases.


Keywords: type 1 diabetes; age of diagnosis; sex; parental origin of alleles PMID:10699054

  8. Inhibition of inflammation by pentosan polysulfate impedes the development and progression of severe diabetic nephropathy in aging C57B6 mice.

    PubMed

    Wu, Jin; Guan, Tian-jun; Zheng, Shirong; Grosjean, Fabrizio; Liu, Weicheng; Xiong, Huabao; Gordon, Ronald; Vlassara, Helen; Striker, Gary E; Zheng, Feng

    2011-10-01

    Inflammation has a key role in diabetic nephropathy (DN) progression. Pentosan polysulfate (PPS) has been shown to decreases interstitial inflammation and glomerulosclerosis in 5/6 nephrectomized rats. Since PPS has an excellent long-term safety profile in interstitial cystitis treatment, and we recently found that old diabetic C57B6 mice develop DN characterized by extensive tubulointerstitial inflammatory lesions that mimics human DN, we examined the effect of PPS on old diabetic mice. We also examined the anti-inflammatory properties of PPS in renal cells in vitro. Diabetes was induced with streptozotocin in 18 months female (early aging) C57B6 mice. Mice were then randomized to receive oral PPS (25 mg/kg/day) or water for 4 months. The effect of PPS on NF-κB activation and on TNFα, high glucose or advanced glycation end products (AGEs) stimulated proinflammatory gene expression in renal cells was examined. We found that PPS treatment preserved renal function, significantly reduced albuminuria, and markedly decreased the severity of renal lesions, including tubulointerstitial inflammation. PPS also reduced upregulation of TNFα and proinflammatory genes in aging diabetic kidneys. Furthermore, PPS suppressed NF-κB, decreased the proinflammatory actions of TNFα, and decreased high glucose and AGEs stimulated MCP-1 production in vitro. Finally, PPS decreased TNFα-induced increase in albumin permeability in podocyte monolayers. In conclusion, PPS treatment largely prevents the development/progression of nephropathy in aging diabetic mice. As this may be mediated by suppression of TNFα, high glucose, and AGE-stimulated NF-κB activation and inflammation in vitro, the in vivo blockade of DN may be due to the anti-inflammatory properties of PPS.

  9. Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss.

    PubMed

    Barber, Alistair J

    2015-06-01

    Diabetic retinopathy (DR) is one of the most common retinal diseases world-wide. It has a complex pathology that involves the vasculature of the inner retina and breakdown of the blood-retinal barrier. Extensive research has determined that DR is not only a vascular disease but also has a neurodegenerative component and that essentially all types of cells in the retina are affected, leading to chronic loss of visual function. A great deal of work using animal models of DR has established the loss of neurons and pathology of other cell types, including supporting glial cells. There has also been an increased emphasis on measuring retinal function in the models, as well as further validation and extension of the animal studies by clinical and translational research. This article will attempt to summarize the more recent developments in research towards understanding the complexities of retinal neurodegeneration and functional vision loss in DR.

  10. Improvements in IVF in women of advanced age.

    PubMed

    Gleicher, Norbert; Kushnir, Vitaly A; Albertini, David F; Barad, David H

    2016-07-01

    Women above age 40 years in the US now represent the most rapidly growing age group having children. Patients undergoing in vitro fertilization (IVF) are rapidly aging in parallel. Especially where egg donations are legal, donation cycles, therefore, multiply more rapidly than autologous IVF cycles. The donor oocytes, however, are hardly ever a preferred patient choice. Since with use of own eggs, live birth rates decline with advancing age but remain stable (and higher) with donor eggs, older patients always face the difficult and very personal choice between poorer chances with own and better chances with donor oocytes. Physician contribution to this decision should in our opinion be restricted to accurate outcome information for both options. Achievable pregnancy and live birth rates in older women are, however, frequently underestimated, thereby mistakenly biasing fertility providers, private insurance companies and even regulatory government agencies. Restriction on access to IVF for older women is then often the consequence. In this review, we summarize the limited published data on best treatments of 'older' ovaries, while also addressing treatment approaches that should be avoided in older women. This focused review, therefore, to a degree is subjective. Research addressing aging ovaries in IVF has been disappointingly sparse, and has in our opinion too heavily concentrated on methods of embryo selection (ES), which, especially in older women, not only fail to improve IVF outcomes, but actually, negatively affect live birth chances. We conclude that, aside from breakthroughs in gamete creation, only pharmacological interventions into early (small growing follicle stages) follicle maturation will offer new potential to positively impact oocyte and embryo quality and, therefore, IVF outcomes. Research, therefore, should be accordingly redirected.

  11. Detection of erythrocytes influenced by aging and type 2 diabetes using atomic force microscope

    SciTech Connect

    Jin, Hua; Xing, Xiaobo; Zhao, Hongxia; Chen, Yong; Huang, Xun; Ma, Shuyuan; Ye, Hongyan; Cai, Jiye

    2010-01-22

    The pathophysiological changes of erythrocytes are detected at the molecular scale, which is important to reveal the onset of diseases. Type 2 diabetes is an age-related metabolic disorder with high prevalence in elderly (or old) people. Up to now, there are no treatments to cure diabetes. Therefore, early detection and the ability to monitor the progression of type 2 diabetes are very important for developing effective therapies. Type 2 diabetes is associated with high blood glucose in the context of insulin resistance and relative insulin deficiency. These abnormalities may disturb the architecture and functions of erythrocytes at molecular scale. In this study, the aging- and diabetes-induced changes in morphological and biomechanical properties of erythrocytes are clearly characterized at nanometer scale using atomic force microscope (AFM). The structural information and mechanical properties of the cell surface membranes of erythrocytes are very important indicators for determining the healthy, diseased or aging status. So, AFM may potentially be developed into a powerful tool in diagnosing diseases.

  12. Evidence of gene-gene interaction and age-at-diagnosis effects in type 1 diabetes.

    PubMed

    Howson, Joanna M M; Cooper, Jason D; Smyth, Deborah J; Walker, Neil M; Stevens, Helen; She, Jin-Xiong; Eisenbarth, George S; Rewers, Marian; Todd, John A; Akolkar, Beena; Concannon, Patrick; Erlich, Henry A; Julier, Cécile; Morahan, Grant; Nerup, Jørn; Nierras, Concepcion; Pociot, Flemming; Rich, Stephen S

    2012-11-01

    The common genetic loci that independently influence the risk of type 1 diabetes have largely been determined. Their interactions with age-at-diagnosis of type 1 diabetes, sex, or the major susceptibility locus, HLA class II, remain mostly unexplored. A large collection of more than 14,866 type 1 diabetes samples (6,750 British diabetic individuals and 8,116 affected family samples of European descent) were genotyped at 38 confirmed type 1 diabetes-associated non-HLA regions and used to test for interaction of association with age-at-diagnosis, sex, and HLA class II genotypes using regression models. The alleles that confer susceptibility to type 1 diabetes at interleukin-2 (IL-2), IL2/4q27 (rs2069763) and renalase, FAD-dependent amine oxidase (RNLS)/10q23.31 (rs10509540), were associated with a lower age-at-diagnosis (P = 4.6 × 10⁻⁶ and 2.5 × 10⁻⁵, respectively). For both loci, individuals carrying the susceptible homozygous genotype were, on average, 7.2 months younger at diagnosis than those carrying the protective homozygous genotypes. In addition to protein tyrosine phosphatase nonreceptor type 22 (PTPN22), evidence of statistical interaction between HLA class II genotypes and rs3087243 at cytotoxic T-lymphocyte antigen 4 (CTLA4)/2q33.2 was obtained (P = 7.90 × 10⁻⁵). No evidence of differential risk by sex was obtained at any loci (P ≥ 0.01). Statistical interaction effects can be detected in type 1 diabetes although they provide a relatively small contribution to our understanding of the familial clustering of the disease. PMID:22891215

  13. The role of pharmacogenetics and advances in gene therapy in the treatment of diabetic retinopathy.

    PubMed

    Agarwal, Aniruddha; Ingham, Sally A; Harkins, Keegan A; Do, Diana V; Nguyen, Quan Dong

    2016-02-01

    Diabetic retinopathy (DR) and its complications such as diabetic macular edema continue to remain a major cause for legal blindness in the developed world. While the introduction of anti-tVEGF agents has significantly improved visual outcomes of patients with DR, unpredictable response, largely due to genetic polymorphisms, appears to be a challenge with this therapy. With advances in identification of various genetic biomarkers, novel therapeutic strategies consisting of gene transfer are being developed and tested for patients with DR. Application of pharmacogenetic principles appears to be a promising futuristic strategy to attenuate diabetes-mediated retinal vasculopathy. In this comprehensive review, data from recent studies in the field of pharmacogenomics for the treatment of DR have been provided. PMID:26807609

  14. The role of pharmacogenetics and advances in gene therapy in the treatment of diabetic retinopathy.

    PubMed

    Agarwal, Aniruddha; Ingham, Sally A; Harkins, Keegan A; Do, Diana V; Nguyen, Quan Dong

    2016-02-01

    Diabetic retinopathy (DR) and its complications such as diabetic macular edema continue to remain a major cause for legal blindness in the developed world. While the introduction of anti-tVEGF agents has significantly improved visual outcomes of patients with DR, unpredictable response, largely due to genetic polymorphisms, appears to be a challenge with this therapy. With advances in identification of various genetic biomarkers, novel therapeutic strategies consisting of gene transfer are being developed and tested for patients with DR. Application of pharmacogenetic principles appears to be a promising futuristic strategy to attenuate diabetes-mediated retinal vasculopathy. In this comprehensive review, data from recent studies in the field of pharmacogenomics for the treatment of DR have been provided.

  15. Plasma levels of advanced glycation endproducts are associated with type 1 diabetes and coronary artery calcification

    PubMed Central

    2013-01-01

    Background Advanced glycation endproducts (AGEs) may play a role in the development of coronary artery calcification (CAC) in type 1 diabetes (T1DM). We studied plasma AGEs in association with T1DM and CAC, and whether or not the latter association could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED). Methods We studied 165 individuals with and 169 without T1DM. CAC was quantified in a CAC score based on CT-scanning. Plasma levels of protein-bound pentosidine, Nϵ-(carboxymethyl)lysine (CML) and Nϵ-(carboxyethyl)lysine (CEL) were measured with HPLC/UPLC with fluorescence detection or tandem-mass spectrometry. Tetrahydropyrimidine (THP) was measured with ELISA, as were HsCRP, and sVCAM-1 and vWF, as markers for LGI and ED, respectively. Associations were analyzed with ANCOVA and adjusted for age, sex, BMI, waist-to-hip ratio, smoking, blood pressure, lipid profile, eGFR and T1DM. Results Individuals with T1DM had higher plasma levels of pentosidine, CML and THP compared with controls; means (95% CI) were 0.69 (0.65-0.73) vs. 0.51 (0.48-0.54) nmol/mmol LYS, p < 0.001; 105 (102–107) vs. 93 (90–95) nmol/mmol LYS, p < 0.001; and 126 (118–134) vs. 113 (106–120) U/mL, p = 0.03, respectively. Levels of pentosidine were higher in individuals with T1DM with a moderate to high compared with a low CAC score, means (95% CI) were 0.81 (0.70-0.93) vs. 0.67 (0.63-0.71) nmol/mmol LYS, p = 0.03, respectively. This difference was not attenuated by adjustment for LGI or ED. Conclusions We found a positive association between pentosidine and CAC in T1DM. These results may indicate that AGEs are possibly involved in the development of CAC in individuals with T1DM. PMID:24134530

  16. Suppression of antioxidant Nrf-2 and downstream pathway in H9c2 cells by advanced glycation end products (AGEs) via ERK phosphorylation.

    PubMed

    Ko, Shun-Yao; Chang, Shu-Shing; Lin, I-Hsuan; Chen, Hong-I

    2015-11-01

    Diabetic cardiomyopathy is related to oxidative stress and correlated with the presence of advanced glycation end products (AGEs). In a clinical setting, AGEs can be detected in patients presenting diabetic cardiomyopathy; however, the underlying mechanism has yet to be elucidated. In our previous study, AGEs increase cell hypertrophy via ERK phosphorylation in a process closely related to ROS production. Thus, we propose that AGEs regulate the antioxidant gene nuclear factor-erythroid 2-related factor (Nrf-2). In H9c2 cells treated with AGEs, the expression of Nrf-2 was reduced; however, ERK phosphorylation was shown to increase. Treatment with H2O2 was also shown to increase Nrf-2 and ERK phosphorylation. In cells pretreatment with ROS scavenger NAC, the effects of H2O2 were reduced; however, the effects of the AGEs remained largely unchanged. Conversely, when cells were pretreated with PD98059 (ERK inhibitor), the expression of Nrf-2 was recovered following treatment with AGEs. Our results suggest that AGEs inhibit Nrf-2 via the ERK pathway; however, this influence is partly associated with ROS. Our finding further indicated that AGEs possess both ROS-dependent and ROS-independent pathways, resulting in a reduction in Nrf-2. This report reveals an important mechanism underlying the regulation of diabetic cardiomyopathy progression by AGEs. PMID:26212730

  17. Cavernous antioxidant effect of green tea, epigallocatechin-3-gallate with/without sildenafil citrate intake in aged diabetic rats.

    PubMed

    Mostafa, T; Sabry, D; Abdelaal, A M; Mostafa, I; Taymour, M

    2013-08-01

    This study aimed to assess the cavernous antioxidant effect of green tea (GT), epigallocatechin-3-gallate (EGCG) with/without sildenafil citrate intake in aged diabetic rats. One hundred and four aged male white albino rat were divided into controls that received ordinary chow, streptozotocin (STZ)-induced aged diabetic rats, STZ-induced diabetic rats on infused green tea, induced diabetic rats on epigallocatechin-3-gallate and STZ-induced diabetic rats on sildenafil citrate added to EGCG. After 8 weeks, dissected cavernous tissues were assessed for gene expression of eNOS, cavernous malondialdehyde (MDA), glutathione peroxidase (GPx), cyclic guanosine monophosphate (cGMP), and serum testosterone (T). STZ-induced diabetic rats on GT demonstrated significant increase in cavernous eNOS, cGMP, GPx and significant decrease in cavernous MDA compared with diabetic rats. Diabetic rats on EGCG demonstrated significant increase in cavernous eNOS, cGMP, GPx and significant decrease in cavernous MDA compared with diabetic rats or diabetic rats on GT. Diabetic rats on EGCG added to sildenafil showed significant increase in cavernous eNOS, cGMP and significant decrease in cavernous MDA compared with other groups. Serum T demonstrated nonsignificant difference between the investigated groups. It is concluded that GT and EGCG have significant cavernous antioxidant effects that are increased if sildenafil is added.

  18. Advanced maternal age and risk perception: A qualitative study

    PubMed Central

    2012-01-01

    Background Advanced maternal age (AMA) is associated with several adverse pregnancy outcomes, hence these pregnancies are considered to be “high risk.” A review of the empirical literature suggests that it is not clear how women of AMA evaluate their pregnancy risk. This study aimed to address this gap by exploring the risk perception of pregnant women of AMA. Methods A qualitative descriptive study was undertaken to obtain a rich and detailed source of explanatory data regarding perceived pregnancy risk of 15 women of AMA. The sample was recruited from a variety of settings in Winnipeg, Canada. In-depth interviews were conducted with nulliparous women aged 35 years or older, in their third trimester, and with singleton pregnancies. Interviews were recorded and transcribed verbatim, and content analysis was used to identify themes and categories. Results Four main themes emerged: definition of pregnancy risk, factors influencing risk perception, risk alleviation strategies, and risk communication with health professionals. Conclusions Several factors may influence women's perception of pregnancy risk including medical risk, psychological elements, characteristics of the risk, stage of pregnancy, and health care provider’s opinion. Understanding these influential factors may help health professionals who care for pregnant women of AMA to gain insight into their perspectives on pregnancy risk and improve the effectiveness of risk communication strategies with this group. PMID:22988825

  19. Toxic action of advanced glycation end products on cultured retinal capillary pericytes and endothelial cells: relevance to diabetic retinopathy.

    PubMed

    Chibber, R; Molinatti, P A; Rosatto, N; Lambourne, B; Kohner, E M

    1997-02-01

    The toxic effects of advanced glycation end products (AGEs) on bovine retinal capillary pericytes (BRP) and endothelial cells (BREC) were studied. AGE-modified bovine serum albumin (AGE-BSA) was toxic to BRP. At a concentration of 500 micrograms/ml it reduced the BRP number to 48 +/- 3% (p < 0.05) of untreated controls, as determined by cell counting with haemocytometer. AGE-BSA was also toxic to bovine aortic endothelial cells (BAEC) reducing cell number to 84 +/- 3.1% of untreated controls. Under similar conditions, low concentrations (62.5 micrograms/ml) of AGE-BSA were mitogenic to BREC increasing the cell proliferation to 156 +/- 11% (p < 0.05) above that of untreated controls. At a higher dose of 500 micrograms/ml AGE-BSA decreased the proliferation of BREC to 85 +/- 6% of untreated controls. Immunoblot analysis demonstrated that BRP and BREC express the p60 AGE-receptor. Retinal capillary bed from the human also stained positively for the p60 AGE-receptor. Addition of 0.25 micrograms/ml of p60 AGE-receptor antibody was able to block the effects of AGE-BSA on BRP and BREC. The level of binding of [125I]-labelled AGE-BSA to the cell surface was small but significant among the three cell types. There was also an increase in the internalized pool of radioligand in BRP and BREC but this was very much lower than in BAEC. In all the cell types the internalized pool of [125I]-labelled AGE-BSA was much larger than the amount associated with the cell surface. Degradation products were not detected in the media over the 24-h incubation of the cells with [125I]AGE-BSA. The binding of [125I]-labelled AGE-BSA to the cell surface was prevented by the addition of p60 AGE-receptor. These results suggest that the interaction of AGE-modified proteins with the membrane-bound AGE-receptor may play an important role in the pathogenesis of diabetic retinopathy.

  20. Sarcopenia: a potential cause and consequence of type 2 diabetes in Australia's ageing population?

    PubMed

    Scott, David; de Courten, Barbora; Ebeling, Peter R

    2016-10-01

    The incidence of type 2 diabetes is increasing in Australia's older adult population. Sarcopenia, the age-related decline in skeletal muscle mass, quality and function, may make a significant but under-appreciated contribution to increasing the risk of type 2 diabetes. As skeletal muscle is the largest insulin-sensitive tissue in the body, low muscle mass in sarcopenia likely results in reduced capacity for glucose disposal. Age-related declines in muscle quality, including increased mitochondrial dysfunction and fat infiltration, are also implicated in skeletal muscle inflammation and subsequent insulin resistance. Prospective studies have shown that low muscle mass and strength are associated with increased risk of incident type 2 diabetes. Prevalent type 2 diabetes also appears to exacerbate progression of sarcopenia in older adults. Recently developed operational definitions and the inclusion of sarcopenia in the International classification of diseases, 10th revision, clinical modification, provide impetus for clinicians to diagnose and treat sarcopenia in older patients. Simple assessments to diagnose sarcopenia can potentially play a role in primary and secondary prevention of type 2 diabetes in older patients. Lifestyle modification programs for older adults with type 2 diabetes, particularly for those with sarcopenia, should incorporate progressive resistance training, along with adequate intakes of protein and vitamin D, which may improve both functional and metabolic health and prevent undesirable decreases in muscle mass associated with weight loss interventions. As some older adults with type 2 diabetes have a poor response to exercise, clinicians must ensure that lifestyle modification programs are appropriately prescribed, regularly monitored and modified if necessary. PMID:27681976

  1. Duration of Abdominal Obesity Beginning in Young Adulthood and Incident Diabetes Through Middle Age

    PubMed Central

    Reis, Jared P.; Hankinson, Arlene L.; Loria, Catherine M.; Lewis, Cora E.; Powell-Wiley, Tiffany; Wei, Gina S.; Liu, Kiang

    2013-01-01

    OBJECTIVE To examine whether the duration of abdominal obesity determined prospectively using measured waist circumference (WC) is associated with the development of new-onset diabetes independent of the degree of abdominal adiposity. RESEARCH DESIGN AND METHODS The Coronary Artery Risk Development in Young Adults Study is a multicenter, community-based, longitudinal cohort study of 5,115 white and black adults aged 18–30 years in 1985 to 1986. Years spent abdominally obese were calculated for participants without abdominal obesity (WC >102 cm in men and >88 cm in women) or diabetes at baseline (n = 4,092) and was based upon repeat measurements conducted 2, 5, 7, 10, 15, 20, and 25 years later. RESULTS Over 25 years, 392 participants developed incident diabetes. Overall, following adjustment for demographics, family history of diabetes, study center, and time varying WC, energy intake, physical activity, smoking, and alcohol, each additional year of abdominal obesity was associated with a 4% higher risk of developing diabetes [hazard ratio (HR) 1.04 (95% CI 1.02–1.07)]. However, a quadratic model best represented the data. HRs for 0, 1–5, 6–10, 11–15, 16–20, and >20 years of abdominal obesity were 1.00 (referent), 2.06 (1.43–2.98), 3.45 (2.28–5.22), 3.43 (2.28–5.22), 2.80 (1.73–4.54), and 2.91 (1.60–5.29), respectively; P-quadratic < 0.001. CONCLUSIONS Longer duration of abdominal obesity was associated with substantially higher risk for diabetes independent of the degree of abdominal adiposity. Preventing or at least delaying the onset of abdominal obesity in young adulthood may lower the risk of developing diabetes through middle age. PMID:23248193

  2. The Effects of Intensive Nutrition Education on Late Middle-Aged Adults with Type 2 Diabetes

    PubMed Central

    Li, Ye; Xu, Meihong; Fan, Rui; Ma, Xiaotao; Gu, Jiaojiao; Cai, Xiaxia; Liu, Rui; Chen, Qihe; Ren, Jinwei; Mao, Ruixue; Bao, Lei; Zhang, Zhaofeng; Wang, Junbo; Li, Yong

    2016-01-01

    Objective: Many patients with type 2 diabetes find it difficult to maintain good glycemic control. Undesirable glycemic control occurs greatly due to deficiencies of nutritional knowledge and difficulty in obtaining dietary prescriptions. The late middle-aged and elder individuals are the main populations that are affected by type 2 diabetes. The main purpose of this study was to investigate whether intensive nutrition education would make benefits for late middle-aged patients with type 2 diabetes. Method: 196 patients between 50 to 65 years old meeting type 2 diabetes criteria and eligible for the program were included in a single-blinded, 30-day centralized management of an education program in China. Participants in the program were randomly divided into a usual nutrition education group or an intensive nutrition education group. The usual nutrition education group was used as a control group and received only basic health advice and principles of diabetic diets at the beginning and the end of the study. Participants in the intensive nutrition education group were arranged to receive intensive nutritional lectures about diabetes for 30 days. The primary outcomes were the changes in weight, body mass index (BMI), fasting plasma glucose (FPG), 2-h postprandial plasma glucose (PG), glycosylated hemoglobin (HbA1c), total glycerin (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c). Results: After 30 days of intervention, FPG, PG, and HbA1c in the treatment group decreased significantly than the control group (p < 0.05). HbA1c reduced significantly by 0.6% in the intervention group. No significant differences in the change of blood lipids were observed between groups. However, TG, TC, and HDL-c made improvements compared with the baseline in the experimental group. Both groups had a reduction in weight and BMI within groups, especially in intensive nutrition education group. However, there was

  3. HbA1c and serum levels of advanced glycation and oxidation protein products in poorly and well controlled children and adolescents with type 1 diabetes mellitus.

    PubMed

    Kostolanská, Jana; Jakus, Vladimír; Barák, L'ubomír

    2009-05-01

    Diabetes mellitus is associated with hyperglycemia and with accelerated non-enzymatic glycation, increased oxidative stress and free radical production. The aim of the present study was to evaluate the levels of proteins glycation and oxidation parameters, compare them between poorly and well controlled children with type 1 diabetes mellitus, and determine the impact of glycemic control on these parameters. Blood and serum were obtained from 81 patients with type 1 diabetes mellitus (DM1) (20 patients had long-term good glycemic control [GGC], 61 patients had long-term poor glycemic control [PGC]). Thirty-one healthy children were used as controls. Fructosamine (FAM) was determined by a spectrophotometric method, HbA1c was measured by LPLC, serum advanced glycation end-products (s-AGEs) were determined fluorimetrically, and advanced oxidation protein products (AOPP) were measured spectrophotometrically. We observed significantly higher FAM, HbA1c, s-AGEs and AOPP levels in the patients with DM1 compared with controls, and significantly higher FAM, HbA1c and sAGEs levels in the PGC group compared with the GGC group. AOPP was higher in the PGC group than in the GGC group, but not significantly. In the PGC group we observed significant correlations between HbA1c and HDL-C (r = -0.306, p = 0.01), HbA1c and s-AGEs (r = 0.486, p < 0.001), and HbA1c and AOPP (r = 0.447, p < 0.01). s-AGEs significantly correlated with triacylglycerols (TAG) (r = 0.537, p < 0.001) and AOPP with HDL-C (r = -0.336, p < 0.05), TAG (r = 0.739, p < 0.001) and s-AGEs (r = 0.577, p < 0.001). In conclusion, our results showed both glycative and oxidative stress are increased in the PGC diabetic group compared with controls, they are linked with glycemic control, and probably contribute to the development of diabetic complications. We suggest that the measurement of not only HbA1c but also s-AGEs and AOPP may be useful to predict the risk of development of diabetic complications.

  4. Acceptance Factors of Mobile Apps for Diabetes by Patients Aged 50 or Older: A Qualitative Study

    PubMed Central

    Reichelt, Julius; Bellmann, Maike; Kirch, Wilhelm

    2015-01-01

    Background Mobile apps for people with diabetes offer great potential to support therapy management, increase therapy adherence, and reduce the probability of the occurrence of accompanying and secondary diseases. However, they are rarely used by elderly patients due to a lack of acceptance. Objective We investigated the question “Which factors influence the acceptance of diabetes apps among patients aged 50 or older?” Particular emphasis was placed on the current use of mobile devices/apps, acceptance-promoting/-inhibiting factors, features of a helpful diabetes app, and contact persons for technical questions. This qualitative study was the third of three substudies investigating factors influencing acceptance of diabetes apps among patients aged 50 or older. Methods Guided interviews were chosen in order to get a comprehensive insight into the subjective perspective of elderly diabetes patients. At the end of each interview, the patients tested two existing diabetes apps to reveal obstacles in (first) use. Results Altogether, 32 patients with diabetes were interviewed. The mean age was 68.8 years (SD 8.2). Of 32 participants, 15 (47%) knew apps, however only 2 (6%) had already used a diabetes app within their therapy. The reasons reported for being against the use of apps were a lack of additional benefits (4/8, 50%) compared to current therapy management, a lack of interoperability with other devices/apps (1/8, 12%), and no joy of use (1/8, 12%). The app test revealed the following main difficulties in use: nonintuitive understanding of the functionality of the apps (26/29, 90%), nonintuitive understanding of the menu navigation/labeling (19/29, 66%), font sizes and representations that were too small (14/29, 48%), and difficulties in recognizing and pressing touch-sensitive areas (14/29, 48%). Furthermore, the patients felt the apps lacked individually important functions (11/29, 38%), or felt the functions that were offered were unnecessary for their own

  5. Advancing age progressively affects obstacle avoidance skills in the elderly.

    PubMed

    Weerdesteyn, Vivian; Nienhuis, Bart; Duysens, Jacques

    2005-01-01

    The ability to adequately avoid obstacles while walking is an important skill that allows safe locomotion over uneven terrain. The high proportion of falls in the elderly that is associated to tripping over obstacles potentially illustrates an age-related deterioration of this locomotor skill. Some studies have compared young and old adults, but very little is known about the changes occurring within different age groups of elderly. In the present study, obstacle avoidance performance was studied in 25 young (20-37 years) and 99 older adults (65-88 years). The participants walked on a treadmill at a speed of 3 km/h. An obstacle was dropped 30 times in front of the left foot at various phases in the step cycle. Success rates (successful avoidance) were calculated and related to the time available between obstacle appearance and the estimated instant of foot contact with the obstacle (available response times or ARTs ranging from 200 to more than 350 ms). In addition, latencies of avoidance reactions, the choice of avoidance strategies (long or short step strategy, LSS or SSS), and three spatial parameters related to obstacle avoidance (toe distance, foot clearance, and heel distance) were determined for each participant. Compared to the young, the older adults had lower success rates, especially at short ARTs. Furthermore, they had longer reaction times, more LSS reactions, smaller toe and heel distances, and larger foot clearances. Within the group of elderly, only the 65-69 year olds were not different from young adults with respect to success rate, despite marked changes in the other parameters measured. In particular, even this younger group of elderly showed a dramatic reduction in the amount of SSS trials compared to young adults. Overall, age was a significant predictor of success rates, reaction times, and toe distances. These parameters deteriorated with advancing age. Finally, avoidance success rates at short ARTs were considerably worse in elderly

  6. Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema.

    PubMed

    Emerson, M Vaughn; Lauer, Andreas K

    2007-01-01

    Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) are the leading causes of vision loss in the industrialized world. The mainstay of treatment for both conditions has been thermal laser photocoagulation, while there have been recent advances in the treatment of CNV using photodynamic therapy with verteporfin. While both of these treatments have prevented further vision loss in a subset of patients, vision improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF aptamer, prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a full-length humanized monoclonal antibody against VEGF, have both shown promising results, with improvements in visual acuity in the treatment of both diseases. VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than all other anti-VEGF therapies, and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering RNA to inhibit VEGF production and VEGF receptor production. Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment and prevention of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Initial results are also encouraging for other growth factors, including pigment epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin, which decreases protein

  7. Diabetic retinopathy - ocular complications of diabetes mellitus

    PubMed Central

    Nentwich, Martin M; Ulbig, Michael W

    2015-01-01

    In industrialized nations diabetic retinopathy is the most frequent microvascular complication of diabetes mellitus and the most common cause of blindness in the working-age population. In the next 15 years, the number of patients suffering from diabetes mellitus is expected to increase significantly. By the year 2030, about 440 million people in the age-group 20-79 years are estimated to be suffering from diabetes mellitus worldwide (prevalence 7.7%), while in 2010 there were 285 million people with diabetes mellitus (prevalence 6.4%). This accounts for an increase in patients with diabetes in industrialized nations by 20% and in developing countries by 69% until the year 2030. Due to the expected rise in diabetic patients, the need for ophthalmic care of patients (i.e., exams and treatments) will also increase and represents a challenge for eye-care providers. Development of optimized screening programs, which respect available resources of the ophthalmic infrastructure, will become even more important. Main reasons for loss of vision in patients with diabetes mellitus are diabetic macular edema and proliferative diabetic retinopathy. Incidence or progression of these potentially blinding complications can be greatly reduced by adequate control of blood glucose and blood pressure levels. Additionally, regular ophthalmic exams are mandatory for detecting ocular complications and initiating treatments such as laser photocoagulation in case of clinical significant diabetic macular edema or early proliferative diabetic retinopathy. In this way, the risk of blindness can considerably be reduced. In advanced stages of diabetic retinopathy, pars-plana vitrectomy is performed to treat vitreous hemorrhage and tractional retinal detachment. In recent years, the advent of intravitreal medication has improved therapeutic options for patients with advanced diabetic macular edema. PMID:25897358

  8. Television viewing time and risk of incident diabetes mellitus: the English Longitudinal Study of Ageing

    PubMed Central

    Smith, L; Hamer, M

    2014-01-01

    Aim To investigate the longitudinal association between television viewing time and risk of incident diabetes mellitus in an elderly sample of adults in England. Methods Analyses of data from the English Longitudinal Study of Ageing. At baseline (2008), participants reported their television viewing time and physical activity level. Diabetes mellitus was recorded from self-reported physician diagnosis at 2-year follow-up. Associations between television viewing time and combined television viewing time and physical activity level with risk of incident diabetes mellitus at follow-up were examined using adjusted logistic regression models. Results A total of 5964 participants (mean ± sd age 65 ± 9 years at baseline, 44% male) were included in the analyses. There was an association between baseline television viewing time and risk of incident diabetes mellitus at 2-year follow-up (≥ 6 h/day compared with <2 h/day; odds ratio 4.27, 95% CI 1.69, 10.77), although the association was attenuated to the null in final adjusted models that included BMI. Participants who were inactive/had high television viewing time at baseline were almost twice as likely to have diabetes mellitus at 2-year follow-up than those who were active/had low television viewing time (fully adjusted odds ratio 1.94, 95% CI 1.02, 3.68), although active participants reporting high television viewing were not at risk. Conclusion Interventions to reduce the incidence of diabetes in the elderly that focus on both increasing physical activity and reducing television viewing time might prove useful. PMID:24975987

  9. Recent advances on the development of wound dressings for diabetic foot ulcer treatment--a review.

    PubMed

    Moura, Liane I F; Dias, Ana M A; Carvalho, Eugénia; de Sousa, Hermínio C

    2013-07-01

    Diabetic foot ulcers (DFUs) are a chronic, non-healing complication of diabetes that lead to high hospital costs and, in extreme cases, to amputation. Diabetic neuropathy, peripheral vascular disease, abnormal cellular and cytokine/chemokine activity are among the main factors that hinder diabetic wound repair. DFUs represent a current and important challenge in the development of novel and efficient wound dressings. In general, an ideal wound dressing should provide a moist wound environment, offer protection from secondary infections, remove wound exudate and promote tissue regeneration. However, no existing dressing fulfills all the requirements associated with DFU treatment and the choice of the correct dressing depends on the wound type and stage, injury extension, patient condition and the tissues involved. Currently, there are different types of commercially available wound dressings that can be used for DFU treatment which differ on their application modes, materials, shape and on the methods employed for production. Dressing materials can include natural, modified and synthetic polymers, as well as their mixtures or combinations, processed in the form of films, foams, hydrocolloids and hydrogels. Moreover, wound dressings may be employed as medicated systems, through the delivery of healing enhancers and therapeutic substances (drugs, growth factors, peptides, stem cells and/or other bioactive substances). This work reviews the state of the art and the most recent advances in the development of wound dressings for DFU treatment. Special emphasis is given to systems employing new polymeric biomaterials, and to the latest and innovative therapeutic strategies and delivery approaches. PMID:23542233

  10. Recent advances on the development of wound dressings for diabetic foot ulcer treatment--a review.

    PubMed

    Moura, Liane I F; Dias, Ana M A; Carvalho, Eugénia; de Sousa, Hermínio C

    2013-07-01

    Diabetic foot ulcers (DFUs) are a chronic, non-healing complication of diabetes that lead to high hospital costs and, in extreme cases, to amputation. Diabetic neuropathy, peripheral vascular disease, abnormal cellular and cytokine/chemokine activity are among the main factors that hinder diabetic wound repair. DFUs represent a current and important challenge in the development of novel and efficient wound dressings. In general, an ideal wound dressing should provide a moist wound environment, offer protection from secondary infections, remove wound exudate and promote tissue regeneration. However, no existing dressing fulfills all the requirements associated with DFU treatment and the choice of the correct dressing depends on the wound type and stage, injury extension, patient condition and the tissues involved. Currently, there are different types of commercially available wound dressings that can be used for DFU treatment which differ on their application modes, materials, shape and on the methods employed for production. Dressing materials can include natural, modified and synthetic polymers, as well as their mixtures or combinations, processed in the form of films, foams, hydrocolloids and hydrogels. Moreover, wound dressings may be employed as medicated systems, through the delivery of healing enhancers and therapeutic substances (drugs, growth factors, peptides, stem cells and/or other bioactive substances). This work reviews the state of the art and the most recent advances in the development of wound dressings for DFU treatment. Special emphasis is given to systems employing new polymeric biomaterials, and to the latest and innovative therapeutic strategies and delivery approaches.

  11. Adverse Effects of Diabetes Mellitus on the Skeleton of Aging Mice.

    PubMed

    Portal-Núñez, Sergio; Ardura, Juan Antonio; Lozano, Daniel; Bolívar, Oskarina Hernández; López-Herradón, Ana; Gutiérrez-Rojas, Irene; Proctor, Alexander; van der Eerden, Bram; Schreuders-Koedam, Marijke; van Leeuwen, Johannes; Alcaraz, María José; Mulero, Francisca; de la Fuente, Mónica; Esbrit, Pedro

    2016-03-01

    In the present study, the possibility that a diabetic (DM) status might worsen age-related bone deterioration was explored in mice. Male CD-1 mice aged 2 (young control group) or 16 months, nondiabetic or made diabetic by streptozotocin injections, were used. DM induced a decrease in bone volume, trabecular number, and eroded surface, and in mineral apposition and bone formation rates, but an increased trabecular separation, in L1-L3 vertebrae of aged mice. Three-point bending and reference point indentation tests showed slight changes pointing to increased frailty and brittleness in the mouse tibia of diabetic old mice. DM was related to a decreased expression of both vascular endothelial growth factor and its receptor 2, which paralleled that of femoral vasculature, and increased expression of the pro-adipogenic gene peroxisome proliferator-activated receptor γ and adipocyte number, without affecting β-catenin pathway in old mouse bone. Concomitant DM in old mice failed to affect total glutathione levels or activity of main anti-oxidative stress enzymes, although xanthine oxidase was slightly increased, in the bone marrow, but increased the senescence marker caveolin-1 gene. In conclusion, DM worsens bone alterations of aged mice, related to decreased bone turnover and bone vasculature and increased senescence, independently of the anti-oxidative stress machinery. PMID:26386012

  12. Adverse Effects of Diabetes Mellitus on the Skeleton of Aging Mice.

    PubMed

    Portal-Núñez, Sergio; Ardura, Juan Antonio; Lozano, Daniel; Bolívar, Oskarina Hernández; López-Herradón, Ana; Gutiérrez-Rojas, Irene; Proctor, Alexander; van der Eerden, Bram; Schreuders-Koedam, Marijke; van Leeuwen, Johannes; Alcaraz, María José; Mulero, Francisca; de la Fuente, Mónica; Esbrit, Pedro

    2016-03-01

    In the present study, the possibility that a diabetic (DM) status might worsen age-related bone deterioration was explored in mice. Male CD-1 mice aged 2 (young control group) or 16 months, nondiabetic or made diabetic by streptozotocin injections, were used. DM induced a decrease in bone volume, trabecular number, and eroded surface, and in mineral apposition and bone formation rates, but an increased trabecular separation, in L1-L3 vertebrae of aged mice. Three-point bending and reference point indentation tests showed slight changes pointing to increased frailty and brittleness in the mouse tibia of diabetic old mice. DM was related to a decreased expression of both vascular endothelial growth factor and its receptor 2, which paralleled that of femoral vasculature, and increased expression of the pro-adipogenic gene peroxisome proliferator-activated receptor γ and adipocyte number, without affecting β-catenin pathway in old mouse bone. Concomitant DM in old mice failed to affect total glutathione levels or activity of main anti-oxidative stress enzymes, although xanthine oxidase was slightly increased, in the bone marrow, but increased the senescence marker caveolin-1 gene. In conclusion, DM worsens bone alterations of aged mice, related to decreased bone turnover and bone vasculature and increased senescence, independently of the anti-oxidative stress machinery.

  13. The influence of age on the management of patients with diabetes in the Israeli population.

    PubMed

    Tirosh, Amit; Stern, Zvi; Mazar, Marianna; Calderon-Margalit, Ronit

    2013-08-01

    The authors' aim was to study the association between age and the quality of community health care of diabetes mellitus (DM). This was a cross-sectional study of patients with DM in the setting of a large health maintenance organization (HMO) in Israel. The population included DM patients aged 40-84 years who were identified at emergency rooms or through the HMO's computerized database. A set of quality care indicators were determined. Logistic regressions were used to estimate the odds ratios (OR) for diabetes care indicators, controlling for age and other potential confounders. Older patients were more likely to be in the target range of glycemic control and to be vaccinated against influenza. Patients older than age 70 years received fewer recommendations for physical activity (OR 0.41, P<0.01) and self-foot examination (OR 0.57, P=0.024). The authors found decreased performance of recommendations for physical activity and self-foot examination, and a higher performance of annual blood tests and immunizations among elderly patients with diabetes.

  14. Age at the time of sulfonylurea initiation influences treatment outcomes in KCNJ11-related neonatal diabetes

    PubMed Central

    Thurber, Brian W.; Carmody, David; Tadie, Elizabeth C.; Pastore, Ashley N.; Dickens, Jazzmyne T.; Wroblewski, Kristen E.; Naylor, Rochelle N.; Philipson, Louis H.; Greeley, Siri Atma W.

    2015-01-01

    Aims/hypothesis Individuals with heterozygous activating mutations of the KCNJ11 gene encoding a subunit of the ATP-sensitive potassium channel (KATP) can usually be treated with oral sulfonylurea (SU) pills in lieu of insulin injections. The aim of this study was to test our hypothesis that younger age at the time of initiation of SU therapy is correlated with lower required doses of SU therapy, shorter transition time and decreased likelihood of requiring additional diabetes medications. Methods We performed a retrospective cohort study using data on 58 individuals with neonatal diabetes due to KCNJ11mutations identified through the University of Chicago Monogenic Diabetes Registry (http://monogenicdiabetes.uchicago.edu/registry). We assessed the influence of age at initiation of SU therapy on treatment outcomes. Results HbA1c fell from an average of 8.5% (69 mmol/mol) before transition to 6.2% (44 mmol/mol) after SU therapy (p < 0.001). Age of initiation of SU correlated with the dose (mg kg−1 day−1) of SU required at follow-up (r = 0.80, p < 0.001). Similar associations were observed across mutation subtypes. Ten participants required additional glucose-lowering medications and all had initiated SU at age 13 years or older. No serious adverse events were reported. Conclusions/interpretation Earlier age at initiation of SU treatment is associated with improved response to SU therapy. Declining sensitivity to SU may be due to loss of beta cell mass over time in those treated with insulin. Our data support the need for early genetic diagnosis and appropriate personalised treatment in all cases of neonatal diabetes. PMID:25877689

  15. Pulsatile Stress in Middle-Aged Patients With Type 1 or Type 2 Diabetes Compared With Nondiabetic Control Subjects

    PubMed Central

    Philips, Jean-Christophe; Marchand, Monique; Scheen, André J.

    2010-01-01

    OBJECTIVE Arterial pulse pressure is considered to be an independent cardiovascular risk factor. We compared pulse pressure during an active orthostatic test in middle-aged patients with type 1 diabetes and with type 2 diabetes and corresponding nondiabetic control subjects. RESEARCH DESIGN AND METHODS Forty patients with type 1 diabetes (mean age 50 years, diabetes duration 23 years, and BMI 23.0 kg/m2) were compared with 40 nonhypertensive patients with type 2 diabetes (respectively, 50 years, 8 years, and 29.7 kg/m2). Patients taking antihypertensive agents or with renal insufficiency were excluded. All patients were evaluated with a continuous noninvasive arterial blood pressure monitoring (Finapres) in standing (1 min), squatting (1 min), and again standing position (1 min). Patients with type 1 or type 2 diabetes were compared with two groups of 40 age-, sex- and BMI-matched healthy subjects. RESULTS Patients with type 1 diabetes and patients with type 2 diabetes showed significantly higher pulse pressure, heart rate, and double product of pulse pressure and heart rate (PP×HR) (type 1: 5,263 vs. 4,121 mmHg/min, P = 0.0004; type 2: 5,359 vs. 4,321 mmHg, P = 0.0023) levels than corresponding control subjects. There were no significant differences between patients with type 1 diabetes and type 2 diabetes regarding pulse pressure (59 vs. 58 mmHg), heart rate (89 vs. 88/min), and PP×HR (5,263 vs. 5,359 mmHg/min). CONCLUSIONS Patients with type 1 diabetes have increased levels of peripheral PP, an indirect marker of arterial stiffness, and PP×HR, an index of pulsatile stress, comparable to those of nonhypertensive patients with type 2 diabetes at similar mean age of 50 years. PMID:20693351

  16. International Forum for the Advancement of Diabetes Research and Care, April 29-30, 2011, Athens, Greece.

    PubMed

    Bolli, Geremia B; Deeb, Larry C; Garg, Satish K; Leahy, John L; Mazze, Roger S; Owens, David R; Riddle, Matthew C; Southerland, Phil; Strock, Ellie S

    2011-09-01

    The International Forum for the Advancement of Diabetes Research and Care brought together distinguished international experts in diabetes to discuss diverse trends and emerging issues in diabetes therapy and management. The plenary sessions on the first day focused on trends in insulin therapy, the role of glucagon-like peptide-1 receptor agonists in diabetes treatment, the relationship between diabetes and cardiovascular risk, and the challenges associated with the development of clinically relevant treatment guidelines. Interactive breakout sessions addressed the following topics: microvascular complications of diabetes; the need for a team approach to patient education; optimal management of Asian people with diabetes; the role of continuous glucose monitoring in assessing glucose variability; and lessons learned from biosimilar drugs. The plenary sessions on the second day covered self-monitoring of blood glucose, treatment and prevention of type 1 diabetes, and future directions for diabetes therapy. The meeting represented an excellent forum for the presentation of new research and the exchange of ideas aimed at improving outcomes for people with diabetes.

  17. International Forum for the Advancement of Diabetes Research and Care, April 29–30, 2011, Athens, Greece

    PubMed Central

    Deeb, Larry C.; Garg, Satish K.; Leahy, John L.; Mazze, Roger S.; Owens, David R.; Riddle, Matthew C.; Southerland, Phil; Strock, Ellie S.

    2011-01-01

    Abstract The International Forum for the Advancement of Diabetes Research and Care brought together distinguished international experts in diabetes to discuss diverse trends and emerging issues in diabetes therapy and management. The plenary sessions on the first day focused on trends in insulin therapy, the role of glucagon-like peptide-1 receptor agonists in diabetes treatment, the relationship between diabetes and cardiovascular risk, and the challenges associated with the development of clinically relevant treatment guidelines. Interactive breakout sessions addressed the following topics: microvascular complications of diabetes; the need for a team approach to patient education; optimal management of Asian people with diabetes; the role of continuous glucose monitoring in assessing glucose variability; and lessons learned from biosimilar drugs. The plenary sessions on the second day covered self-monitoring of blood glucose, treatment and prevention of type 1 diabetes, and future directions for diabetes therapy. The meeting represented an excellent forum for the presentation of new research and the exchange of ideas aimed at improving outcomes for people with diabetes. PMID:21864094

  18. Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model.

    PubMed

    Park, Se Eun; Park, Cheol-Young; Choi, Jung Mook; Chang, Eugene; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki Won; Park, Sung Woo; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo

    2016-01-01

    Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation.

  19. Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model

    PubMed Central

    Park, Se Eun; Choi, Jung Mook; Chang, Eugene; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki Won; Park, Sung Woo; Kang, Eun Seok; Lee, Hyun Chul

    2016-01-01

    Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation. PMID:26894429

  20. Correlates of Physical Activity Among Middle-Aged and Older Korean Americans at Risk for Diabetes

    PubMed Central

    Han, Benjamin; Sadarangani, Tina; Wyatt, Laura C.; Zanowiak, Jennifer M.; Kwon, Simona C.; Trinh-Shevrin, Chau; Lee, Linda; Islam, Nadia S.

    2016-01-01

    Purpose To explore correlates of meeting recommended physical activity (PA) among middle-aged and older Korean Americans at risk for diabetes mellitus (DM). Design and Methods PA patterns and their correlates were assessed among 292 middle-aged and older Korean Americans at risk for DM living in New York City (NYC) using cross-sectional design of baseline information from a diabetes prevention intervention. PA was assessed by self-report of moderate and vigorous activity, results were stratified by age group (45-64 and 65-75), and bivariate analyses compared individuals performing less than sufficient PA and individuals performing sufficient PA. Logistic regression was used to calculate adjusted odds ratios predicting sufficient PA. Findings After adjusting for sex, age group, years lived in United States, marital status, health insurance and body mass index (BMI), sufficient PA was associated with male sex, older age, lower BMI, eating vegetables daily, and many PA-specific questions (lack of barriers, confidence, and engagement). When stratified by age group, male sex and eating vegetables daily was no longer significant among Koreans age 65 to 75 years of age, and BMI was not significant for either age group. Conclusions PA interventions targeting this population may be beneficial and should consider the roles of sex, age, physical and social environment, motivation, and self-efficacy. Clinical Relevance Clinical providers should understand the unique motivations for PA among Korean Americans and recognize the importance of culturally driven strategies to enable lifestyle changes and support successful aging for diverse populations. PMID:26641597

  1. Mobile phone technologies and advanced data analysis towards the enhancement of diabetes self-management.

    PubMed

    Kouris, Ioannis; Mougiakakou, Stavroula; Scarnato, Luca; Iliopoulou, Dimitra; Diem, Peter; Vazeou, Andriani; Koutsouris, Dimitris

    2010-01-01

    Advances in the area of mobile and wireless communication for healthcare (m-Health) along with the improvements in information science allow the design and development of new patient-centric models for the provision of personalised healthcare services, increase of patient independence and improvement of patient's self-control and self-management capabilities. This paper comprises a brief overview of the m-Health applications towards the self-management of individuals with diabetes mellitus and the enhancement of their quality of life. Furthermore, the design and development of a mobile phone application for Type 1 Diabetes Mellitus (T1DM) self-management is presented. The technical evaluation of the application, which permits the management of blood glucose measurements, blood pressure measurements, insulin dosage, food/drink intake and physical activity, has shown that the use of the mobile phone technologies along with data analysis methods might improve the self-management of T1DM.

  2. Hearing Loss as a Function of Aging and Diabetes Mellitus: A Cross Sectional Study

    PubMed Central

    Park, Dong Choon; Kim, MyungGu; Chung, Ji Hyun; Kim, Sang Hoon; Yeo, Seung Geun

    2014-01-01

    Background Although hearing loss may be caused by various factors, it is also a natural phenomenon associated with the aging process. This study was designed to assess the contributions of diabetes mellitus (DM) and hypertension, both chronic diseases associated with aging, as well as aging itself, to hearing loss in health screening examinees. Methods This study included 37,773 individuals who underwent health screening examinations from 2009 to 2012. The relationships between hearing threshold and subject age, hearing threshold at each frequency based on age group, the degree of hearing loss and the presence or absence of hypertension and DM were evaluated. Results The prevalence of hearing loss increased with age, being 1.6%, 1.8%, 4.6%, 14.0%, 30.8%, and 49.2% in subjects in their twenties, thirties, forties, fifties, sixties, and seventies, respectively (p<0.05). Hearing value per frequency showed aging-based changes, in the order of 6000, 4000, 2000, 1000 and 500 Hz, indicating greater hearing losses at high frequencies. The degree of hearing loss ranged from mild to severe. Aging and DM were correlated with the prevalence of hearing loss (p<0.05). There was no statistically significant association between hearing loss and hypertension after adjusting for age and DM. Conclusions The prevalence of hearing loss increases with age and the presence of DM. Hearing loss was greatest at high frequencies. In all age groups, mild hearing loss was the most common form of hearing loss. PMID:25549095

  3. Cardiovascular disease and type 1 diabetes: prevalence, prediction and management in an ageing population

    PubMed Central

    Lee, Siang Ing; Patel, Mitesh; Jones, Christopher M.; Narendran, Parth

    2015-01-01

    Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes mellitus (T1D). However, evidence of its risks and management is often extrapolated from studies in type 2 diabetic (T2D) patients or the general population. This approach is unsatisfactory given that the underlying pathology, demographics and natural history of the disease differ between T1D and T2D. Furthermore, with a rising life expectancy, a greater number of T1D patients are exposed to the cardiovascular (CV) risk factors associated with an ageing population. The aim of this review is to examine the existing literature around CVD in T1D. We pay particular attention to CVD prevalence, how well we manage risk, potential biomarkers, and whether the studies included the older aged patients (defined as aged over 65). We also discuss approaches to the management of CV risk in the older aged. The available data suggest a significant CVD burden in patients with T1D and poor management of CV risk factors. This is underpinned by a poor evidence base for therapeutic management of CV risk specifically for patients with T1D, and in the most relevant population – the older aged patients. We would suggest that important areas remain to be addressed, particularly exploring the risks and benefits of therapeutic approaches to CVD management in the older aged. PMID:26568811

  4. Beneficial effects through aggressive coronary screening for type 2 diabetes patients with advanced vascular complications.

    PubMed

    Tsujimoto, Tetsuro; Sugiyama, Takehiro; Yamamoto-Honda, Ritsuko; Kishimoto, Miyako; Noto, Hiroshi; Morooka, Miyako; Kubota, Kazuo; Kamimura, Munehiro; Hara, Hisao; Kajio, Hiroshi; Kakei, Masafumi; Noda, Mitsuhiko

    2016-08-01

    Glycemic control alone does not reduce cardiovascular events in patients with type 2 diabetes (T2D), and routine screening of all T2D patients for asymptomatic coronary artery disease (CAD) is not effective for preventing acute cardiac events. We examined the effectiveness of an aggressive screening protocol for asymptomatic CAD in T2D patients with advanced vascular complications.We designed a 3-year cohort study investigating the effectiveness of the aggressive coronary screening for T2D patients with advanced vascular complications and no known coronary events using propensity score adjusted analysis at a national center in Japan. Eligibility criteria included T2D without known coronary events and with any 1 of the following 4 complications: advanced diabetic retinopathy, advanced chronic kidney disease, peripheral artery disease, or cerebrovascular disease. In the aggressive screening group (n = 122), all patients received stress single photon emission computed tomography and those exhibiting myocardial perfusion abnormalities underwent coronary angiography. In the conventional screening group (n = 108), patients were examined for CAD at the discretion of their medical providers. Primary endpoint was composite outcome of cardiovascular death and nonfatal cardiovascular events.Asymptomatic CAD with ≥70% stenosis was detected in 39.3% of patients completing aggressive screening. The proportions achieving revascularization and receiving intensive medical therapy within 90 days after the screening were significantly higher in the aggressive screening group than in the conventional screening group [19.7% vs 0% (P < 0.001) and 48.4% vs 9.3% (P < 0.001), respectively]. The cumulative rate of primary composite outcome was significantly lower in the aggressive screening group according to a propensity score adjusted Cox proportional hazards model (hazard ratio, 0.35; 95% confidence interval, 0.12-0.96; P = 0.04).Aggressive coronary screening for T2D patients

  5. Effects of glucagon-like peptide-1 on advanced glycation endproduct-induced aortic endothelial dysfunction in streptozotocin-induced diabetic rats: possible roles of Rho kinase- and AMP kinase-mediated nuclear factor κB signaling pathways.

    PubMed

    Tang, Song-Tao; Zhang, Qiu; Tang, Hai-Qin; Wang, Chang-Jiang; Su, Huan; Zhou, Qing; Wei, Wei; Zhu, Hua-Qing; Wang, Yuan

    2016-07-01

    Interaction between advanced glycation endproducts (AGEs) and receptor for AGEs (RAGE) as well as downstream pathways leads to vascular endothelial dysfunction in diabetes. Glucagon-like peptide-1 (GLP-1) has been reported to attenuate endothelial dysfunction in the models of atherosclerosis. However, whether GLP-1 exerts protective effects on aortic endothelium in diabetic animal model and the underlying mechanisms are still not well defined. Experimental diabetes was induced through administration with combination of high-fat diet and intraperitoneal injection of streptozotocin. Rats were randomly divided into four groups, including controls, diabetes, diabetes + sitagliptin (30 mg/kg/day), diabetes + exenatide (3 μg/kg/12 h). Eventually, endothelial damage, markers of inflammation and oxidative stress, were measured. After 12 weeks administration, diabetic rats received sitagliptin and exenatide showed significant elevation of serum NO level and reduction of ET-1 as well as inflammatory cytokines levels. Moreover, sitagliptin and exenatide significantly inhibited aortic oxidative stress level and improved aortic endothelial function in diabetic rats. Importantly, these drugs inhibited the protein expression level in AGE/RAGE-induced RhoA/ROCK/NF-κB/IκBα signaling pathways and activated AMPK in diabetic aorta. Finally, the target proteins of p-eNOS, iNOS, and ET-1, which reflect endothelial function, were also changed by these drugs. Our present study indicates that sitagliptin and exenatide administrations can improve endothelial function in diabetic aorta. Of note, RAGE/RhoA/ROCK and AMPK mediated NF-κB signaling pathways may be the intervention targets of these drugs to protect aortic endothelium. PMID:26758998

  6. Physical Disability Trajectories in Older Americans with and without Diabetes: The Role of Age, Gender, Race or Ethnicity, and Education

    ERIC Educational Resources Information Center

    Chiu, Ching-Ju; Wray, Linda A.

    2011-01-01

    Purpose: This research combined cross-sectional and longitudinal data to characterize age-related trajectories in physical disability for adults with and without diabetes in the United States and to investigate if those patterns differ by age, gender, race or ethnicity, and education. Design and Methods: Data were examined on 20,433 adults aged 51…

  7. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

    SciTech Connect

    Matsui, Takanori; Yamagishi, Sho-ichi; Takeuchi, Masayoshi; Ueda, Seiji; Fukami, Kei; Okuda, Seiya

    2009-07-24

    The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}). Although nifedipine did not affect expression levels of PPAR-{gamma}, it increased the PPAR-{gamma} transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-{gamma} activation.

  8. Influence of Age on Incident Diabetes and Cardiovascular Disease in Prostate Cancer Survivors Receiving Androgen Deprivation Therapy

    PubMed Central

    Morgans, Alicia K.; Fan, Kang-Hsien; Koyama, Tatsuki; Albertsen, Peter C.; Goodman, Michael; Hamilton, Ann S.; Hoffman, Richard M.; Stanford, Janet L.; Stroup, Antoinette M.; Resnick, Matthew J.; Barocas, Daniel A.; Penson, David F.

    2015-01-01

    Purpose Observational data suggest that androgen deprivation therapy increases the risk of diabetes and cardiovascular disease. Using data from the population based PCOS we evaluated whether age at diagnosis and comorbidity impact the association of androgen deprivation therapy with incident diabetes and cardiovascular disease. Materials and Methods We identified men with nonmetastatic prostate cancer diagnosed from 1994 to 1995 who were followed through 2009 to 2010. We used multivariable logistic regression models to assess the relationship of androgen deprivation therapy exposure (2 or fewer years, greater than 2 years or none) with incident diabetes and cardiovascular disease, adjusting for age at diagnosis, race, stage and comorbidity. Results Of 3,526 eligible study participants 2,985 without diabetes and 3,112 without cardiovascular disease comprised the cohorts at risk. Androgen deprivation therapy was not associated with an increased risk of diabetes or cardiovascular disease in men diagnosed with prostate cancer before age 70 years. Prolonged androgen deprivation therapy and increasing age at diagnosis in older men was associated with an increased risk of diabetes (at age 76 years OR 2.1, 95% CI 1.0–4.4) and cardiovascular disease (at age 74 years OR 1.9, 95% CI 1.0–3.5). Men with comorbidities were at greater risk for diabetes (OR 4.3, 95% CI 2.3–7.9) and cardiovascular disease (OR 8.1, 95% CI 4.3–15.5) than men without comorbidities. Conclusions Prolonged androgen deprivation therapy exposure increases the risk of cardiovascular disease and diabetes in men diagnosed with prostate cancer who are older than approximately 75 years, especially those with other comorbidities. Older men who receive prolonged androgen deprivation therapy should be closely monitored for diabetes and cardiovascular disease. PMID:25451829

  9. Diabetic retinopathy.

    PubMed

    Wong, Tien Y; Cheung, Chui Ming Gemmy; Larsen, Michael; Sharma, Sanjay; Simó, Rafael

    2016-01-01

    Diabetic retinopathy (DR) is a common complication of diabetes mellitus and is a major cause of vision loss in middle-aged and elderly people. One-third of people with diabetes have DR. Severe stages of DR include proliferative DR, caused by the abnormal growth of new retinal blood vessels, and diabetic macular oedema, in which there is exudation and oedema in the central part of the retina. DR is strongly associated with a prolonged duration of diabetes, hyperglycaemia and hypertension. It is traditionally regarded as a microvascular disease, but retinal neurodegeneration is also involved. Complex interrelated pathophysiological mechanisms triggered by hyperglycaemia underlie the development of DR. These mechanisms include genetic and epigenetic factors, increased production of free radicals, advanced glycosylation end products, inflammatory factors and vascular endothelial growth factor (VEGF). Optimal control of blood glucose and blood pressure in individuals with diabetes remains the cornerstone for preventing the development and arresting the progression of DR. Anti-VEGF therapy is currently indicated for diabetic macular oedema associated with vision loss, whereas laser photocoagulation prevents severe vision loss in eyes with proliferative DR. These measures, together with increasing public awareness and access to regular screening for DR with retinal photography, and the development of new treatments to address early disease stages, will lead to better outcomes and prevent blindness for patients with DR. PMID:27159554

  10. Solution structure of the variable-type domain of the receptor for advanced glycation end products: new insight into AGE-RAGE interaction.

    PubMed

    Matsumoto, Shigeyuki; Yoshida, Takuya; Murata, Hiroko; Harada, Shusaku; Fujita, Naoko; Nakamura, Shota; Yamamoto, Yasuhiko; Watanabe, Takuo; Yonekura, Hideto; Yamamoto, Hiroshi; Ohkubo, Tadayasu; Kobayashi, Yuji

    2008-11-25

    Diabetes is defined by chronic hyperglycemia due to deficiency in insulin action. It has been found that the amount of advanced glycation end products (AGE) from the Maillard reaction between proteins and sugar molecules increases in blood of diabetic patients and furthermore that AGE binding to their cell surface receptor (RAGE) triggers both macrovascular and microvascular impairments to cause diabetic complications. Due to the clinical significance of the vascular complications, RAGE is currently a focus as an attractive target for drug discovery of candidates which interfere with AGE-RAGE binding to prevent the subsequent intracellular signaling related to pathogenical effects. Here, we determined the three-dimensional structure of the recombinant AGE-binding domain by using multidimensional heteronuclear NMR spectroscopy and showed that the domain assumes a structure similar to those of other immunoglobulin V-type domains. The site-directed mutagenesis studies identified the basic amino acids which play a key role in the AGE binding activities. Our results obtained from this study provide new insight into AGE-RAGE interaction. PMID:19032093

  11. Glycated Hemoglobin and Outcomes in Patients with Advanced Diabetic Chronic Kidney Disease

    PubMed Central

    Kuo, I-Ching; Lin, Hugo You-Hsien; Niu, Sheng-Wen; Hwang, Daw-Yang; Lee, Jia-Jung; Tsai, Jer-Chia; Hung, Chi-Chih; Hwang, Shang-Jyh; Chen, Hung-Chun

    2016-01-01

    Diabetes is the major risk factor for end-stage renal disease (ESRD) worldwide. In advanced chronic kidney disease (CKD), less is known about the predictive value of HbA1c. We enrolled 2401 diabetic patients with stage 3–4 and stage 5 CKD, who were classified into 4 groups according to their baseline HbA1c values (<6%, 6%–7%, 7%–9%, and >9%). During the median follow-up of 3 years, 895 patients developed ESRD, and 530 died. In linear regression analysis, higher HbA1c correlated with higher eGFR in patients with stage 5 CKD but not in stage 3–4 CKD. In Cox regression analysis, a trend toward worse clinical outcomes existed when the HbA1c level exceeded 6% in stage 3–4 CKD, but the significance was only observed for >9%. The hazard ratios (HRs) for ESRD, all-cause mortality and combined CV events with mortality in the group of HbA1c >9% were 1.6 (95% CI, 1.07 to 2.38), 1.52 (95% CI, 0.97 to 2.38) and 1.46 (95% CI, 1.02 to 2.09), respectively. This study demonstrates that the higher HbA1c level is associated higher risks for clinical outcomes in diabetic patients with stage 3–4 CKD but not in stage 5 CKD. PMID:26818011

  12. The use of an extract of Hypericum perforatum and Azadirachta indica in advanced diabetic foot: an unexpected outcome

    PubMed Central

    Iabichella, Maria Letizia

    2013-01-01

    This is the first case reporting the results of using an extract of Hypericum flowers (Hypericum perforatum) and neem oil (Azadirachta indica) in foot wounds with exposed bone in a patient with bilateral advanced diabetic ulcers. The effective use of this cheap treatment in patients with diabetic lesions on the feet, if confirmed in a wide controlled study, might allow the caregivers to take care of patients at home. PMID:23413284

  13. The use of an extract of Hypericum perforatum and Azadirachta indica in advanced diabetic foot: an unexpected outcome.

    PubMed

    Iabichella, Maria Letizia

    2013-01-01

    This is the first case reporting the results of using an extract of Hypericum flowers (Hypericum perforatum) and neem oil (Azadirachta indica) in foot wounds with exposed bone in a patient with bilateral advanced diabetic ulcers. The effective use of this cheap treatment in patients with diabetic lesions on the feet, if confirmed in a wide controlled study, might allow the caregivers to take care of patients at home. PMID:23413284

  14. Diabetes

    MedlinePlus

    ... improved with weight-loss surgery. There is no cure for type 1 diabetes. Treating either type 1 diabetes or type 2 ... a life-long disease and there is no cure. Tight control of blood ... diabetes complications. But these problems can occur, even in ...

  15. Experimental induction of type 2 diabetes in aging-accelerated mice triggered Alzheimer-like pathology and memory deficits.

    PubMed

    Mehla, Jogender; Chauhan, Balwantsinh C; Chauhan, Neelima B

    2014-01-01

    Alzheimer's disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD.

  16. Experimental Induction of Type 2 Diabetes in Aging-Accelerated Mice Triggered Alzheimer-Like Pathology and Memory Deficits

    PubMed Central

    Mehla, Jogender; Chauhan, Balwantsinh C.; Chauhan, Neelima B.

    2014-01-01

    Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD. PMID:24121970

  17. Impaired musculoskeletal response to age and exercise in PPARβ(-/-) diabetic mice.

    PubMed

    Fu, He; Desvergne, Beatrice; Ferrari, Serge; Bonnet, Nicolas

    2014-12-01

    Fragility fractures are recognized complication of diabetes, but yet the underlying mechanisms remain poorly understood. This is particularly pronounced in type 2 diabetes in which the propensity to fall is increased but bone mass is not necessarily low. Thus, whether factors implicated in the development of insulin resistance and diabetes directly impact on the musculoskeletal system remains to be investigated. PPARβ(-/-) mice have reduced metabolic activity and are glucose intolerant. We examined changes in bone and muscle in PPARβ(-/-) mice and investigated both the mechanism behind those changes with age as well as their response to exercise. Compared with their wild type, PPARβ(-/-) mice had an accelerated and parallel decline in both muscle and bone strength with age. These changes were accompanied by increased myostatin expression, low bone formation, and increased resorption. In addition, mesenchymal cells from PPARβ(-/-) had a reduced proliferation capacity and appeared to differentiate into more of an adipogenic phenotype. Concomitantly we observed an increased expression of PPARγ, characteristic of adipocytes. The anabolic responses of muscle and bone to exercise were also diminished in PPARβ(-/-) mice. The periosteal bone formation response to direct bone compression was, however, maintained, indicating that PPARβ controls periosteal bone formation through muscle contraction and/or metabolism. Taken together, these data indicate that PPARβ deficiency leads to glucose intolerance, decreased muscle function, and reduced bone strength. On a molecular level, PPARβ appears to regulate myostatin and PPARγ expression in muscle and bone, thereby providing potential new targets to reverse bone fragility in patients with metabolic disturbances.

  18. Current Advances in the Biochemical and Physiological Aspects of the Treatment of Type 2 Diabetes Mellitus with Thiazolidinediones

    PubMed Central

    Alemán-González-Duhart, D.; Tamay-Cach, F.; Álvarez-Almazán, S.

    2016-01-01

    The present review summarizes the current advances in the biochemical and physiological aspects in the treatment of type 2 diabetes mellitus (DM2) with thiazolidinediones (TZDs). DM2 is a metabolic disorder characterized by hyperglycemia, triggering the abnormal activation of physiological pathways such as glucose autooxidation, polyol's pathway, formation of advance glycation end (AGE) products, and glycolysis, leading to the overproduction of reactive oxygen species (ROS) and proinflammatory cytokines, which are responsible for the micro- and macrovascular complications of the disease. The treatment of DM2 has been directed toward the reduction of hyperglycemia using different drugs such as insulin sensitizers, as the case of TZDs, which are able to lower blood glucose levels and circulating triglycerides by binding to the nuclear peroxisome proliferator-activated receptor gamma (PPARγ) as full agonists. When TZDs interact with PPARγ, the receptor regulates the transcription of different genes involved in glucose homeostasis, insulin resistance, and adipogenesis. However, TZDs exhibit some adverse effects such as fluid retention, weight gain, hepatotoxicity, plasma-volume expansion, hemodilution, edema, bone fractures, and congestive heart failure, which limits their use in DM2 patients. PMID:27313601

  19. PARP INHIBITION OR GENE DEFICIENCY COUNTERACT INTRAEPIDERMAL NERVE FIBER LOSS AND NEUROPATHIC PAIN IN ADVANCED DIABETIC NEUROPATHY

    PubMed Central

    Obrosova, Irina G.; Xu, Weizheng; Lyzogubov, Valeriy V.; Ilnytska, Olga; Mashtalir, Nazar; Vareniuk, Igor; Pavlov, Ivan A.; Zhang, Jie; Slusher, Barbara; Drel, Viktor R.

    2011-01-01

    Evidence for important role of poly(ADP-ribose) polymerase (PARP) activation in diabetic complications is emerging. This study evaluated the role for PARP in rat and mouse models of advanced diabetic neuropathy. The orally active PARP inhibitor 10-(4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]anthracen-3-one(GPI-15427, formulated as mesilate salt, 30 mg kg−1d−1 in the drinking water, for 10 weeks after first 2 weeks without treatment) at least partially prevented PARP activation in peripheral nerve and DRG neurons, as well as thermal hypoalgesia, mechanical hyperalgesia, tactile allodynia, exaggerated response to formalin, and, the most important, intraepidermal nerve fiber degeneration in streptozotocin-diabetic rats. These findings are consistent with the lack of small sensory nerve fiber dysfunction in diabetic PARP−/− mice. Furthermore, whereas diabetic PARP+/+ mice displayed ~ 46% intraepidermal nerve fiber loss, diabetic PARP−/− preserved completely normal intraepidermal nerve fiber density. In conclusion, PARP activation is an important contributor to intraepidermal nerve fiber degeneration and functional changes associated with advanced Type 1 diabetic neuropathy. The results support the rationale for development of potent and low toxic PARP inhibitors and PARP inhibitor-containing combination therapies. PMID:17976390

  20. Effect of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione, isolated from Averrhoa carambola L. (Oxalidaceae) roots, on advanced glycation end-product-mediated renal injury in type 2 diabetic KKAy mice.

    PubMed

    Zheng, Ni; Lin, Xing; Wen, Qingwei; Kintoko; Zhang, Shijun; Huang, Jianchun; Xu, Xiaohui; Huang, Renbin

    2013-05-10

    The roots of Averrhoa carambola L. (Oxalidaceae) have a long history of medical use in traditional Chinese medicine for treating diabetes and diabetic nephropathy. 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) was isolated from the tuberous roots of A. carambola L. The purpose of this study was to investigate the beneficial effect of DMDD on the advanced glycation end-product-mediated renal injury in type 2 diabetic KKAy mice with regard to prove its efficacy by local traditional practitioners in the treatment of kidney frailties in diabetics. KKAy mice were orally administrated DMDD (12.5, 25, 50mg/kg body weight/d) or aminoguanidine (200mg/kg body weight/d) for 8 weeks. Hyperglycemia, renal AGE formation, and the expression of related proteins, such as the AGE receptor, nuclear factor-κB, transforming growth factor-β1, and N(ε)-(carboxymethyl)lysine, were markedly decreased by DMDD. Diabetes-dependent alterations in proteinuria, serum creatinine, creatinine clearance, and serum urea-N and glomerular mesangial matrix expansion were attenuated after treatment with DMDD for 8 weeks. The activities of superoxide dismutase and glutathione peroxidase, which are reduced in the kidneys of KKAy mice, were enhanced by DMDD. These findings suggest that DMDD may inhibit the progression of diabetic nephropathy and may be a therapeutic agent for regulating several pharmacological targets to treat or prevent of diabetic nephropathy.

  1. Advanced glycation end products

    PubMed Central

    Gkogkolou, Paraskevi; Böhm, Markus

    2012-01-01

    Aging is the progressive accumulation of damage to an organism over time leading to disease and death. Aging research has been very intensive in the last years aiming at characterizing the pathophysiology of aging and finding possibilities to fight age-related diseases. Various theories of aging have been proposed. In the last years advanced glycation end products (AGEs) have received particular attention in this context. AGEs are formed in high amounts in diabetes but also in the physiological organism during aging. They have been etiologically implicated in numerous diabetes- and age-related diseases. Strategies inhibiting AGE accumulation and signaling seem to possess a therapeutic potential in these pathologies. However, still little is known on the precise role of AGEs during skin aging. In this review the existing literature on AGEs and skin aging will be reviewed. In addition, existing and potential anti-AGE strategies that may be beneficial on skin aging will be discussed. PMID:23467327

  2. [Comparative characteristics of antioxidant status in women with diabetes type 2 of different age groups].

    PubMed

    Ishonina, O G; Mikashinovich, Z I; Olempieva, E V; Kovalenko, T D

    2011-01-01

    The purpose of this study was to evaluate the metabolic processes in women with diabetes mellitus type 2 of different age groups. It is established that hyperglycemia in aged women is characterized by the development of pronounced oxidative stress, which is the result of changes in the primary structure of protein molecules due to non enzymatic glycosylation of amino acid residues in the active sites. It is known that observed depletion of reduced glutathione pool is associated with high risk of genotoxicity, because it correlates with activation of mitochondrial, chromatin dysfunction and fragmentation of the DNA. In addition, hydroperoxides of polyunsaturated fatty acids formation leads to necrosis and apoptosis. It can be assumed that the diabetes mellitus type 2 triggers processes of apoptosis, which leads to the activation of aging programs and increase the mortality of patients. Obviously, the change in the concentration of thiol antioxidants, as well as the change in concentration of LPO molecular products may be one of the criteria for evaluation of aging and the efficiency of the treatment of patients.

  3. Interactions of hearing loss and Diabetes Mellitus in the middle age CBA/CaJ mouse model of presbycusis

    PubMed Central

    Vasilyeva, Olga N.; Frisina, Susan T.; Zhu, Xiaoxia; Walton, Joseph P.; Frisina, Robert D.

    2009-01-01

    Recently, we characterized the more severe nature of hearing loss in aged Type 2 diabetic human subjects. The current study prospectively assessed hearing abilities in middle age CBA/CaJ mice with Type 1 diabetes mellitus (T1DM) (STZ injection) or Type 2 diabetes mellitus (T2DM) (high fat diet), for a period of 6 months. Blood glucose, body weight and auditory tests (Auditory Brainstem Response-ABR, Distortion Product Otoacoustic Emissions-DPOAE) were evaluated at baseline and every 2 months. Tone and broadband noise-burst responses in the inferior colliculus were obtained at 6 months. Body weights of controls did not change over 6 months (~32g), but there was a significant (~5g) decline in the T1DM, while T2DM exhibited ~10g weight gain. Blood glucose levels significantly increased: 3 fold for T1DM, 1.3 fold for T2DM; with no significant changes in controls. ABR threshold elevations were found for both types of diabetes, but were most pronounced in the T2DM, starting as early as 2 months after induction of diabetes. A decline of mean DPOAE amplitudes was observed in both diabetic groups at high frequencies, and for the T2DM at low frequencies. In contrast to ABR thresholds, tone and noise thresholds in the inferior colliculus were lower for both diabetic groups. Induction of diabetes in middle-aged CBA/CaJ mice promotes amplification of age-related peripheral hearing loss which makes it a suitable model for studying the interaction of age-related hearing loss and diabetes. On the other hand, initial results of effects from very high blood glucose level (T1DM) on the auditory midbrain showed disruption of central inhibition, increased response synchrony or enhanced excitation in the inferior colliculus. PMID:19271313

  4. Prevalence of diabetes mellitus in the population aged 40-69 years in Galicia, northwest Spain.

    PubMed

    Muniz, J; Hervada, J; Juane, R; Lopez-Rodriguez, I; Castro-Beiras, A

    1995-11-01

    A cross-sectional study of the prevalence and distribution of diabetes among 40- to 69-year olds in Galicia (NW Spain) is presented. A (R)Reflotron system was used to measure the capillary fasting glucaemia in 1275 subjects randomly chosen from the electoral roll, who also answered a short questionnaire and were weighed and measured. The prevalence of diabetes was 7.5% regardless of sex or habitat (urban or rural), and increased significantly with age. These data are in keeping with the scant available information from other parts of Spain and the world in general. The lack of difference between urban and rural habitats was unexpected in view of previously reported dietary differences between both areas.

  5. Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease in non diabetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiologic studies indicate that the risks for major age-related debilities including coronary heart disease, diabetes, and age-related macular degeneration (AMD) are diminished in people who consume lower glycemic index (GI) diets, but lack of a unifying physiobiochemical mechanism that explains...

  6. What is more damaging to vascular endothelial function: Diabetes, age, high BMI, or all of the above?

    PubMed Central

    Petrofsky, Jerrold S.; Alshammari, Faris; Bains, Gurinder Singh; Khowailed, Iman Akef; Lee, Haneul; Kuderu, Yashvanth Nagarajamurthy; Lodha, Riya D.; Rodrigues, Sophia; Nguyen, Diamond; Potnis, Pooja Ashok; Deshpande, Pooja P.; Yim, Jong Eun; Berk, Lee

    2013-01-01

    Background It is well established that there is a reduction in the skin blood flow (SBF) in response to heat with age and diabetes. While it is known that high BMI creates a stress on the cardiovascular system and increases the risk of all cause of morbidity and mortality, little is known of the effect of high BMI on SBF response to heat. Since diabetes is associated with age and a higher BMI, the interrelationship between age, BMI and SBF needs to be investigated to better understand the contribution diabetes alone has to endothelial impairment. Material/Methods This study examined the SBF to heat in young and old people with low and high BMI and people with diabetes with high BMI to determine the contribution these variables have on SBF. Subjects were ten young and older people with BMI <20 and ten young and older people with BMI >20 and ten subjects with diabetes with BMI >20. The SBF response, above the quadriceps, was determined during a 6 minutes exposure to heat at 44°C. Results Even in young people, SBF after the stress of heat exposure was reduced in subjects with a high BMI. The effect of BMI was greatest in young people and lowest in older people and people with diabetes; in people with diabetes, BMI was a more significant variable than diabetes in causing impairment of blood flow to heat. BMI, for example, was responsible for 49% of the reduction in blood flow after stress heat exposure (R=−0.7) while ageing only accounted for 16% of the blood flow reduction (R=−0.397). Conclusions These results would suggest the importance of keeping BMI low not only in people with diabetes to minimize further circulatory vascular damage, but also in young people to diminish long term circulatory vascular compromise. PMID:23666370

  7. Lifecourse socioeconomic status and type 2 diabetes: the role of chronic inflammation in the English Longitudinal Study of Ageing

    PubMed Central

    Stringhini, Silvia; Zaninotto, Paola; Kumari, Meena; Kivimäki, Mika; Batty, G. David

    2016-01-01

    We examined the association between lifecourse socioeconomic status (SES) and the risk of type 2 diabetes at older ages, ascertaining the extent to which adult lifestyle factors and systemic inflammation explain this relationship. Data were drawn from the English Longitudinal Study of Ageing (ELSA) which, established in 2002, is a representative cohort study of ≥50-year olds individuals living in England. SES indicators were paternal social class, participants’ education, participants’ wealth, and a lifecourse socioeconomic index. Inflammatory markers (C-reactive protein and fibrinogen) and lifestyle factors were measured repeatedly; diabetes incidence (new cases) was monitored over 7.5 years of follow-up. Of the 6218 individuals free from diabetes at baseline (44% women, mean aged 66 years), 423 developed diabetes during follow-up. Relative to the most advantaged people, those in the lowest lifecourse SES group experienced more than double the risk of diabetes (hazard ratio 2.59; 95% Confidence Interval (CI) = 1.81–3.71). Lifestyle factors explained 52% (95%CI:30–85) and inflammatory markers 22% (95%CI:13–37) of this gradient. Similar results were apparent with the separate SES indicators. In a general population sample, socioeconomic inequalities in the risk of type 2 diabetes extend to older ages and appear to partially originate from socioeconomic variations in modifiable factors which include lifestyle and inflammation. PMID:27101929

  8. Adolescents with Type 1 Diabetes – The Impact of Gender, Age, and Health-Related Functioning on Eating Disorder Psychopathology

    PubMed Central

    Wisting, Line; Bang, Lasse; Skrivarhaug, Torild; Dahl-Jørgensen, Knut; Rø, Øyvind

    2015-01-01

    Objective To investigate correlates of eating disorder psychopathology in adolescent males and females with type 1 diabetes. Method A total of 105 adolescents with type 1 diabetes (42% males), aged 12–20 years, were recruited from the Norwegian Childhood Diabetes Registry in this population-based study. All participants were interviewed with the Child Eating Disorder Examination. Additionally, the Brief Illness Perception Questionnaire, the Adolescent Coping Orientation for Problem Experiences and the Beliefs about Medicines Questionnaire were administered to assess health-related functioning. Clinical data were obtained from the Norwegian Childhood Diabetes Registry. Results Significant gender differences were demonstrated in the pattern of correlates of eating disorder pathology. Among females, eating disorder psychopathology was significantly associated with body mass index adjusted for age and gender, age, insulin restriction, coping, illness perceptions, and perceptions of insulin concern. In a regression model, age, illness perceptions, and insulin restriction remained significantly associated with eating disorder psychopathology, explaining 48% of the variance. None of the variables were associated with eating disorder psychopathology among males. Discussion Greater clinical awareness of illness perceptions, attitudes toward insulin, and insulin restriction may potentially decrease the risk of developing eating disorders among female adolescents with type 1 diabetes, and the subsequent increased morbidity and mortality associated with comorbid type 1 diabetes and eating disorders. PMID:26529593

  9. Prevention of Obesity and Type 2 Diabetes with Aged Citrus Peel (Chenpi) Extract.

    PubMed

    Guo, Jingjing; Tao, Hanlin; Cao, Yong; Ho, Chi-Tang; Jin, Shengkang; Huang, Qingrong

    2016-03-16

    Chenpi is the dry peel of the plant Citrus reticulata Blanco after an aging processing. It has been used as an antidigestive and anti-inflammatory traditional medicine, as well as culinary seasoning and dietary supplement, in China. However, its efficacy and underlying scientific mechanism have not been sufficiently investigated. Chenpi is uniquely enriched with a high content of 5-demethylated polymethoxyflavones (5-OH PMFs). The effect of chenpi extract on improving metabolic features was examined using high-fat diet (HFD)-induced obesity/diabetes mouse model. Oral administration of 0.25 and 0.5% chenpi extract in food over 15 weeks markedly prevented HFD-induced obesity, hepatic steatosis, and diabetic symptoms. The beneficial effect is associated with 5'-adenosine monophosphate-activated protein kinase (AMPK) activation in adipose tissue. Our results indicate that 5-OH PMFs-enriched chenpi extract is effective in preventing obesity and type 2 diabetes, and its effect might be related to improvement in lipid metabolism associated with activation of the AMPK pathway. PMID:26912037

  10. Advanced Glycation End Products (AGE) Potently Induce Autophagy through Activation of RAF Protein Kinase and Nuclear Factor κB (NF-κB).

    PubMed

    Verma, Neeharika; Manna, Sunil K

    2016-01-15

    Advanced glycation end products (AGE) accumulate in diabetic patients and aging people because of high amounts of three- or four-carbon sugars derived from glucose, thereby causing multiple consequences, including inflammation, apoptosis, obesity, and age-related disorders. It is important to understand the mechanism of AGE-mediated signaling leading to the activation of autophagy (self-eating) that might result in obesity. We detected AGE as one of the potent inducers of autophagy compared with doxorubicin and TNF. AGE-mediated autophagy is inhibited by suppression of PI3K and potentiated by the autophagosome maturation blocker bafilomycin. It increases autophagy in different cell types, and that correlates with the expression of its receptor, receptor for AGE. LC3B, the marker for autophagosomes, is shown to increase upon AGE stimulation. AGE-mediated autophagy is partially suppressed by inhibitor of NF-κB, PKC, or ERK alone and significantly in combination. AGE increases sterol regulatory element binding protein activity, which leads to an increase in lipogenesis. Although AGE-mediated lipogenesis is affected by autophagy inhibitors, AGE-mediated autophagy is not influenced by lipogenesis inhibitors, suggesting that the turnover of lipid droplets overcomes the autophagic clearance. For the first time, we provide data showing that AGE induces several cell signaling cascades, like NF-κB, PKC, ERK, and MAPK, that are involved in autophagy and simultaneously help with the accumulation of lipid droplets that are not cleared effectively by autophagy, therefore causing obesity.

  11. Ten-year experience in management of diabetic ketoacidosis and ketosis: 140 episodes at pediatric age.

    PubMed

    Yordam, Nuren; Gönç, E Nazli; Kandemir, Nurgün; Alikaşifoğlu, Ayfer; Ozön, Alev

    2005-01-01

    One hundred and forty episodes in 112 patients (58 boys) with diabetic ketoacidosis (96 episodes) and diabetic ketosis (44 episodes) were studied to elucidate the clinical and laboratory risk factors for altered level of consciousness at presentation and to analyze the outcome of a distinct protocol in the treatment of diabetic ketoacidosis. The patients were analyzed according to demographic data and clinical and laboratory findings at admission. The treatment protocol involved use of 0.45% sodium chloride (NaCl) in 2.5% dextrose as the initial fluid therapy following volume expansion. Dextrose content of the fluid was doubled once the serum glucose level fell below 250 mg/dl. The mean ages at presentation with diabetic ketoacidosis and ketosis were 10.3 +/- 4.4 and 10.2 +/- 4.0 years, respectively. Thirty-one percent of patients had altered consciousness at presentation. The level of consciousness correlated negatively with serum bicarbonate level (r=-0.485; p<0.001). A serum bicarbonate level below 15 mmol/L was a risk factor for altered consciousness. There was no correlation between effective osmolality and the level of consciousness. Serum effective osmolality above 320 mOsm/kg H2O did not appear to be a risk factor for altered consciousness. No mortality or any signs of clinical brain edema were observed in patients treated with the distinct treatment protocol. In conclusion, acidosis appears to be the major factor in the pathogenesis of altered consciousness at presentation. Serum effective osmolality does not seem to be a risk factor as suggested previously. Dextrose added to the infusion fluid early in treatment seems to prevent the development of brain edema, and this may be due to a protective effect of higher osmolality in the resultant solution.

  12. Human mortality at very advanced age might be constant.

    PubMed

    Klemera, P; Doubal, S

    1997-11-01

    An attempt was made to identify the course of the mortality rate at the upper tail of human age. The only known data suitable for this purpose were published by Riggs and Millecchia (J.E. Riggs, R.J. Millecchia, Mech. Ageing Dev. 62 (1992) 191-199) and our analysis follows up their results. By means of mathematical elaboration it was proved that these data imply a constant mortality rate (approx. 25% per year) at ages above 113 years for men and above 116 years for women. Indirect arguments supporting the validity of the source data are discussed. Nevertheless, even if the source data are mistaken, we proved they cannot be the product of purely random errors and our results may contribute to the elucidation of the origin of those systematic errors. PMID:9379712

  13. Development, relative validity, and reliability of a food frequency questionnaire for a case-control study on dietary advanced glycation end products and diabetes complications.

    PubMed

    Luevano-Contreras, Claudia; Durkin, Taylor; Pauls, Maria; Chapman-Novakofski, Karen

    2013-12-01

    Dietary advanced glycation end products (dAGEs) could be involved on diabetes complications, yet their quantification is not standardized. The objective of this study was to design a food frequency questionnaire (FFQ) for dAGEs, and to assess its reliability and validity. For the design, data from 30 subjects was used. The final instrument had 90 food items. To measure reliability and validity, 20 participants with type 2 diabetes filled out twice the FFQ (FFQ-T1, FFQ-T2) and 7-day food records (7-dFR). The Shrout-Fleiss coefficient was 0.98 showing good reliability. For validation, the results for the weighted kappa were 0.55 (moderate agreement) for FFQ-T1 and 0.64 (good agreement) for FFQ-T2, and 75% and 80% of subjects respectively were correctly classified into tertiles; Bland-Altman graphics showed no systematic bias. This FFQ is comparable to 7-dFR for measuring dAGEs. To our knowledge, this is the first questionnaire designed to measure specifically dAGEs.

  14. Evaluation of Ischemia-Modified Albumin, Malondialdehyde, and Advanced Oxidative Protein Products as Markers of Vascular Injury in Diabetic Nephropathy

    PubMed Central

    Ahmad, Afzal; Manjrekar, Poornima; Yadav, Charu; Agarwal, Ashish; Srikantiah, Rukmini Mysore; Hegde, Anupama

    2016-01-01

    AIM This study aimed at evaluation of ischemia-modified albumin (IMA), malondialdehyde (MDA), and advanced oxidative protein products (AOPP) as markers of vascular injury in diabetic nephropathy (DN) with derivation of cutoff values for the same. MATERIALS AND METHODS Study population comprised 60 diabetes patients and 30 controls, with diabetes patients further categorized into three groups based on urine albumin/creatinine ratio (UACR) of <30 mg/g (diabetes without microalbuminuria), 30–300 mg/g (early DN), and >300 mg/g of creatinine (overt DN). Serum IMA, MDA, and AOPP were estimated by enzyme-linked immunosorbent assay; HbA1c, serum creatinine, urine albumin, and urine creatinine were estimated using automated analyzers. Statistical analysis was done using analysis of variance, Pearson’s correlation coefficient, and receiver-operating characteristic curve. RESULTS A statistically significant difference was found in the levels of IMA among patients with early DN (154 ng/mL), diabetes without nephropathy (109.4 ng/mL), and healthy controls (45.7 ng/mL), with highest levels in early DN cases. Similar increase was seen in AOPP as well. A significant correlation was observed between IMA and UACR in diabetes without nephropathy (r = 0.448). CONCLUSION The present study postulates serum IMA as a novel biomarker for the assessment of disease progression in diabetes even before microalbuminuria, and a cutoff point ≥99 ng/mL can be used for detection of early DN. PMID:27158221

  15. Transportation and Aging: A Research Agenda for Advancing Safe Mobility

    ERIC Educational Resources Information Center

    Dickerson, Anne E.; Molnar, Lisa J.; Eby, David W.; Adler, Geri; Bedard, Michel; Berg-Weger, Marla; Classen, Sherrilene; Foley, Daniel; Horowitz, Amy; Kerschner, Helen; Page, Oliver; Silverstein, Nina M.; Staplin, Loren; Trujillo, Leonard

    2007-01-01

    Purpose: We review what we currently know about older driver safety and mobility, and we highlight important research needs in a number of key areas that hold promise for achieving the safety and mobility goals for the aging baby boomers and future generations of older drivers. Design and Methods: Through the use of a framework for transportation…

  16. Recommendations for managing cutaneous disorders associated with advancing age.

    PubMed

    Humbert, Philippe; Dréno, Brigitte; Krutmann, Jean; Luger, Thomas Anton; Triller, Raoul; Meaume, Sylvie; Seité, Sophie

    2016-01-01

    The increasingly aged population worldwide means more people are living with chronic diseases, reduced autonomy, and taking various medications. Health professionals should take these into consideration when managing dermatological problems in elderly patients. Accordingly, current research is investigating the dermatological problems associated with the loss of cutaneous function with age. As cell renewal slows, the physical and chemical barrier function declines, cutaneous permeability increases, and the skin becomes increasingly vulnerable to external factors. In geriatric dermatology, the consequences of cutaneous aging lead to xerosis, skin folding, moisture-associated skin damage, and impaired wound healing. These problems pose significant challenges for both the elderly and their carers. Most often, nurses manage skin care in the elderly. However, until recently, little attention has been paid to developing appropriate, evidence-based, skincare protocols. The objective of this paper is to highlight common clinical problems with aging skin and provide some appropriate advice on cosmetic protocols for managing them. A review of the literature from 2004 to 2014 using PubMed was performed by a working group of six European dermatologists with clinical and research experience in dermatology. Basic topical therapy can restore and protect skin barrier function, which relieves problems associated with xerosis, prevents aggravating moisture-associated skin damage, and enhances quality of life. In conclusion, the authors provide physicians with practical recommendations to assist them in implementing basic skin care for the elderly in an integrated care approach. PMID:26929610

  17. Recommendations for managing cutaneous disorders associated with advancing age

    PubMed Central

    Humbert, Philippe; Dréno, Brigitte; Krutmann, Jean; Luger, Thomas Anton; Triller, Raoul; Meaume, Sylvie; Seité, Sophie

    2016-01-01

    The increasingly aged population worldwide means more people are living with chronic diseases, reduced autonomy, and taking various medications. Health professionals should take these into consideration when managing dermatological problems in elderly patients. Accordingly, current research is investigating the dermatological problems associated with the loss of cutaneous function with age. As cell renewal slows, the physical and chemical barrier function declines, cutaneous permeability increases, and the skin becomes increasingly vulnerable to external factors. In geriatric dermatology, the consequences of cutaneous aging lead to xerosis, skin folding, moisture-associated skin damage, and impaired wound healing. These problems pose significant challenges for both the elderly and their carers. Most often, nurses manage skin care in the elderly. However, until recently, little attention has been paid to developing appropriate, evidence-based, skincare protocols. The objective of this paper is to highlight common clinical problems with aging skin and provide some appropriate advice on cosmetic protocols for managing them. A review of the literature from 2004 to 2014 using PubMed was performed by a working group of six European dermatologists with clinical and research experience in dermatology. Basic topical therapy can restore and protect skin barrier function, which relieves problems associated with xerosis, prevents aggravating moisture-associated skin damage, and enhances quality of life. In conclusion, the authors provide physicians with practical recommendations to assist them in implementing basic skin care for the elderly in an integrated care approach. PMID:26929610

  18. Current state of type 1 diabetes immunotherapy: incremental advances, huge leaps, or more of the same?

    PubMed

    Phillips, Brett; Trucco, Massimo; Giannoukakis, Nick

    2011-01-01

    Thus far, none of the preclinically successful and promising immunomodulatory agents for type 1 diabetes mellitus (T1DM) has conferred stable, long-term insulin independence to diabetic patients. The majority of these immunomodulators are humanised antibodies that target immune cells or cytokines. These as well as fusion proteins and inhibitor proteins all share varying adverse event occurrence and severity. Other approaches have included intact putative autoantigens or autoantigen peptides. Considerable logistical outlays have been deployed to develop and to translate humanised antibodies targeting immune cells, cytokines, and cytokine receptors to the clinic. Very recent phase III trials with the leading agent, a humanised anti-CD3 antibody, call into question whether further development of these biologics represents a step forward or more of the same. Combination therapies of one or more of these humanised antibodies are also being considered, and they face identical, if not more serious, impediments and safety issues. This paper will highlight the preclinical successes and the excitement generated by phase II trials while offering alternative possibilities and new translational avenues that can be explored given the very recent disappointment in leading agents in more advanced clinical trials.

  19. Perceptual restoration of degraded speech is preserved with advancing age.

    PubMed

    Saija, Jefta D; Akyürek, Elkan G; Andringa, Tjeerd C; Başkent, Deniz

    2014-02-01

    Cognitive skills, such as processing speed, memory functioning, and the ability to divide attention, are known to diminish with aging. The present study shows that, despite these changes, older adults can successfully compensate for degradations in speech perception. Critically, the older participants of this study were not pre-selected for high performance on cognitive tasks, but only screened for normal hearing. We measured the compensation for speech degradation using phonemic restoration, where intelligibility of degraded speech is enhanced using top-down repair mechanisms. Linguistic knowledge, Gestalt principles of perception, and expectations based on situational and linguistic context are used to effectively fill in the inaudible masked speech portions. A positive compensation effect was previously observed only with young normal hearing people, but not with older hearing-impaired populations, leaving the question whether the lack of compensation was due to aging or due to age-related hearing problems. Older participants in the present study showed poorer intelligibility of degraded speech than the younger group, as expected from previous reports of aging effects. However, in conditions that induce top-down restoration, a robust compensation was observed. Speech perception by the older group was enhanced, and the enhancement effect was similar to that observed with the younger group. This effect was even stronger with slowed-down speech, which gives more time for cognitive processing. Based on previous research, the likely explanations for these observations are that older adults can overcome age-related cognitive deterioration by relying on linguistic skills and vocabulary that they have accumulated over their lifetime. Alternatively, or simultaneously, they may use different cerebral activation patterns or exert more mental effort. This positive finding on top-down restoration skills by the older individuals suggests that new cognitive training methods

  20. Perceptual restoration of degraded speech is preserved with advancing age.

    PubMed

    Saija, Jefta D; Akyürek, Elkan G; Andringa, Tjeerd C; Başkent, Deniz

    2014-02-01

    Cognitive skills, such as processing speed, memory functioning, and the ability to divide attention, are known to diminish with aging. The present study shows that, despite these changes, older adults can successfully compensate for degradations in speech perception. Critically, the older participants of this study were not pre-selected for high performance on cognitive tasks, but only screened for normal hearing. We measured the compensation for speech degradation using phonemic restoration, where intelligibility of degraded speech is enhanced using top-down repair mechanisms. Linguistic knowledge, Gestalt principles of perception, and expectations based on situational and linguistic context are used to effectively fill in the inaudible masked speech portions. A positive compensation effect was previously observed only with young normal hearing people, but not with older hearing-impaired populations, leaving the question whether the lack of compensation was due to aging or due to age-related hearing problems. Older participants in the present study showed poorer intelligibility of degraded speech than the younger group, as expected from previous reports of aging effects. However, in conditions that induce top-down restoration, a robust compensation was observed. Speech perception by the older group was enhanced, and the enhancement effect was similar to that observed with the younger group. This effect was even stronger with slowed-down speech, which gives more time for cognitive processing. Based on previous research, the likely explanations for these observations are that older adults can overcome age-related cognitive deterioration by relying on linguistic skills and vocabulary that they have accumulated over their lifetime. Alternatively, or simultaneously, they may use different cerebral activation patterns or exert more mental effort. This positive finding on top-down restoration skills by the older individuals suggests that new cognitive training methods

  1. Does Accumulation of Advanced Glycation End Products Contribute to the Aging Phenotype?

    PubMed Central

    Nicklett, Emily J.; Ferrucci, Luigi

    2010-01-01

    Background. Aging is a complex multifactorial process characterized by accumulation of deleterious changes in cells and tissues, progressive deterioration of structural integrity and physiological function across multiple organ systems, and increased risk of death. Methods. We conducted a review of the scientific literature on the relationship of advanced glycation end products (AGEs) with aging. AGEs are a heterogeneous group of bioactive molecules that are formed by the nonenzymatic glycation of proteins, lipids, and nucleic acids. Results. Humans are exposed to AGEs produced in the body, especially in individuals with abnormal glucose metabolism, and AGEs ingested in foods. AGEs cause widespread damage to tissues through upregulation of inflammation and cross-linking of collagen and other proteins. AGEs have been shown to adversely affect virtually all cells, tissues, and organ systems. Recent epidemiological studies demonstrate that elevated circulating AGEs are associated with increased risk of developing many chronic diseases that disproportionally affect older individuals. Conclusions. Based on these data, we propose that accumulation of AGEs accelerate the multisystem functional decline that occurs with aging, and therefore contribute to the aging phenotype. Exposure to AGEs can be reduced by restriction of dietary intake of AGEs and drug treatment with AGE inhibitors and AGE breakers. Modification of intake and circulating levels of AGEs may be a possible strategy to promote health in old age, especially because most Western foods are processed at high temperature and are rich in AGEs. PMID:20478906

  2. Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers.

    PubMed

    Chera, Simona; Baronnier, Delphine; Ghila, Luiza; Cigliola, Valentina; Jensen, Jan N; Gu, Guoqiang; Furuyama, Kenichiro; Thorel, Fabrizio; Gribble, Fiona M; Reimann, Frank; Herrera, Pedro L

    2014-10-23

    Total or near-total loss of insulin-producing β-cells occurs in type 1 diabetes. Restoration of insulin production in type 1 diabetes is thus a major medical challenge. We previously observed in mice in which β-cells are completely ablated that the pancreas reconstitutes new insulin-producing cells in the absence of autoimmunity. The process involves the contribution of islet non-β-cells; specifically, glucagon-producing α-cells begin producing insulin by a process of reprogramming (transdifferentiation) without proliferation. Here we show the influence of age on β-cell reconstitution from heterologous islet cells after near-total β-cell loss in mice. We found that senescence does not alter α-cell plasticity: α-cells can reprogram to produce insulin from puberty through to adulthood, and also in aged individuals, even a long time after β-cell loss. In contrast, before puberty there is no detectable α-cell conversion, although β-cell reconstitution after injury is more efficient, always leading to diabetes recovery. This process occurs through a newly discovered mechanism: the spontaneous en masse reprogramming of somatostatin-producing δ-cells. The juveniles display 'somatostatin-to-insulin' δ-cell conversion, involving dedifferentiation, proliferation and re-expression of islet developmental regulators. This juvenile adaptability relies, at least in part, upon the combined action of FoxO1 and downstream effectors. Restoration of insulin producing-cells from non-β-cell origins is thus enabled throughout life via δ- or α-cell spontaneous reprogramming. A landscape with multiple intra-islet cell interconversion events is emerging, offering new perspectives for therapy.

  3. Effects of Aging and Domain Knowledge on Usability in Small Screen Devices for Diabetes Patients

    NASA Astrophysics Data System (ADS)

    Calero Valdez, André; Ziefle, Martina; Horstmann, Andreas; Herding, Daniel; Schroeder, Ulrik

    Technology acceptance has become a key concept for the successful rollout of technical devices. Though the concept is intensively studied for nearly 20 years now, still, many open questions remain. This especially applies to technology acceptance of older users, which are known to be very sensitive to suboptimal interfaces and show considerable reservations towards the usage of new technology. Mobile small screen technology increasingly penetrates health care and medical applications. This study investigates impacts of aging, technology expertise and domain knowledge on user interaction using the example of diabetes. For this purpose user effectiveness and efficiency have been measured on a simulated small screen device and related to user characteristics, showing that age and technology expertise have a big impact on usability of the device. Furthermore, impacts of user characteristics and success during the trial on acceptance of the device were surveyed and analyzed.

  4. The Influence of Autonomic Dysfunction Associated with Aging and Type 2 Diabetes on Daily Life Activities

    PubMed Central

    Petrofsky, Jerrold; Berk, Lee; Al-Nakhli, Hani

    2012-01-01

    Type 2 diabetes (T2D) and ageing have well documented effects on every organ in the body. In T2D the autonomic nervous system is impaired due to damage to neurons, sensory receptors, synapses and the blood vessels. This paper will concentrate on how autonomic impairment alters normal daily activities. Impairments include the response of the blood vessels to heat, sweating, heat transfer, whole body heating, orthostatic intolerance, balance, and gait. Because diabetes is more prevalent in older individuals, the effects of ageing will be examined. Beginning with endothelial dysfunction, blood vessels have impairment in their ability to vasodilate. With this and synaptic damage, the autonomic nervous system cannot compensate for effectors such as pressure on and heating of the skin. This and reduced ability of the heart to respond to stress, reduces autonomic orthostatic compensation. Diminished sweating causes the skin and core temperature to be high during whole body heating. Impaired orthostatic tolerance, impaired vision and vestibular sensing, causes poor balance and impaired gait. Overall, people with T2D must be made aware and counseled relative to the potential consequence of these impairments. PMID:22566994

  5. Middle-Aged Independent-Living African Americans' Selections for Advance Directives: A Case Study

    ERIC Educational Resources Information Center

    McDaniel, Brenda J.

    2013-01-01

    The purpose of this collective embedded qualitative case study was to examine the perspectives of three middle-aged independent-living African Americans who had participated in the process of advance care planning (ACP) and completed at least two advance directives (ADs), a Durable Power of Attorney for Health Care (DPAHC) and a Living Will (LW).…

  6. The prevalences of impaired fasting glucose and diabetes mellitus in working age men of North China: Anshan Worker Health Survey.

    PubMed

    Liu, Lei; Zhou, Chuang; Du, Hang; Zhang, Kai; Huang, Desheng; Wu, Jingyang

    2014-01-01

    To investigate the prevalence of impaired fasting glucose (IFG) and total diabetes mellitus (DM) including known diabetes and newly diagnosed diabetes in working age men of North China. A cross-section study was conducted at health medical center of Ansteel Group Hospital in Anshan city of China. 37,345 males between 20-60 years of age were recruited in this study. Age-standardized prevalence of IFG and total DM in these working age men were 25.3% and 8.4%, respectively. The prevalence of IFG and total DM increased, as the age progressed. After multinomial logit analysis, age, systolic blood pressure, drinking, smoking, overweight and obesity, total cholesterol, triglycerides, serum creatinine and blood urea nitrogen were independent risk factors for both IFG and DM. The prevalence rate of IFG in Anshan male workers was higher compared with mainland China overall. Diabetes-related education and popularization of DM prevention programs should be actively carried out with age increasing. PMID:24824525

  7. Systematic review and meta-analysis of age at menarche and risk of type 2 diabetes.

    PubMed

    Janghorbani, Mohsen; Mansourian, Marjan; Hosseini, Elham

    2014-08-01

    The relation of early menarche with type 2 diabetes mellitus (T2DM) remains inconsistent across studies. The objective of this systematic review and meta-analysis of published population-based observational studies was to assess the association between age at menarche and T2DM risk. We searched online data bases through December 2013 and examined the reference lists of pertinent articles. Summary relative risks (RRs) with 95 % confidence intervals (CIs) were calculated with a random-effects model. A total of 14 effect estimates from 10 eligible studies (three cross-sectional and seven cohort studies) included 315,428 participants and 22,085 cases of T2DM. Compared with the highest or middle category, women in the lowest category of age at menarche had higher risk of T2DM [summary RR (95 % CI) 1.22 (1.17, 1.28)]. These results were consistent between studies that conducted in the United States and in Europe. The association between age at menarche and T2DM was slightly stronger for cohort than for cross-sectional studies. These findings strongly support an association between younger age at menarche and increased risk of T2DM. Age at menarche may help identify women with increased risk of developing T2DM. PMID:24671509

  8. Electrophysiological Advances on Multiple Object Processing in Aging

    PubMed Central

    Mazza, Veronica; Brignani, Debora

    2016-01-01

    EEG research conducted in the past 5 years on multiple object processing has begun to define how the aging brain tracks the numerosity of the objects presented in the visual field for different goals. We review the recent EEG findings in healthy older individuals (age range: 65–75 years approximately) on perceptual, attentional and memory mechanisms-reflected in the N1, N2pc and contralateral delayed activity (CDA) components of the EEG, respectively-during the execution of a variety of cognitive tasks requiring simultaneous processing of multiple elements. The findings point to multiple loci of neural changes in multi-object analysis, and suggest the involvement of early perceptual mechanisms, attentive individuation and working memory (WM) operations in the neural and cognitive modification due to aging. However, the findings do not simply reflect early impairments with a cascade effect over subsequent stages of stimulus processing, but in fact highlight interesting dissociations between the effects occurring at the various stages of stimulus processing. Finally, the results on older adults indicate the occurrence of neural overactivation in association to good levels of performance in easy perceptual contexts, thus providing some hints on the existence of compensatory phenomena that are associated with the functioning of early perceptual mechanisms. PMID:26973520

  9. Electrophysiological Advances on Multiple Object Processing in Aging.

    PubMed

    Mazza, Veronica; Brignani, Debora

    2016-01-01

    EEG research conducted in the past 5 years on multiple object processing has begun to define how the aging brain tracks the numerosity of the objects presented in the visual field for different goals. We review the recent EEG findings in healthy older individuals (age range: 65-75 years approximately) on perceptual, attentional and memory mechanisms-reflected in the N1, N2pc and contralateral delayed activity (CDA) components of the EEG, respectively-during the execution of a variety of cognitive tasks requiring simultaneous processing of multiple elements. The findings point to multiple loci of neural changes in multi-object analysis, and suggest the involvement of early perceptual mechanisms, attentive individuation and working memory (WM) operations in the neural and cognitive modification due to aging. However, the findings do not simply reflect early impairments with a cascade effect over subsequent stages of stimulus processing, but in fact highlight interesting dissociations between the effects occurring at the various stages of stimulus processing. Finally, the results on older adults indicate the occurrence of neural overactivation in association to good levels of performance in easy perceptual contexts, thus providing some hints on the existence of compensatory phenomena that are associated with the functioning of early perceptual mechanisms. PMID:26973520

  10. Interactions of hearing loss and diabetes mellitus in the middle age CBA/CaJ mouse model of presbycusis.

    PubMed

    Vasilyeva, Olga N; Frisina, Susan T; Zhu, Xiaoxia; Walton, Joseph P; Frisina, Robert D

    2009-03-01

    Recently, we characterized the more severe nature of hearing loss in aged Type 2 diabetic human subjects [Frisina, S.T., Mapes, F., Kim, S., Frisina, D.R., Frisina, R.D., 2006. Characterization of hearing loss in aged type II diabetics. Hear. Res. 211, 103-113]. The current study prospectively assessed hearing abilities in middle age CBA/CaJ mice with Type 1 diabetes mellitus (T1DM) (STZ injection) or Type 2 diabetes mellitus (T2DM) (high fat diet), for a period of 6 months. Blood glucose, body weight and auditory tests (Auditory Brainstem Response-ABR, Distortion Product Otoacoustic Emissions-DPOAE) were evaluated at baseline and every 2 months. Tone and broad-band noise-burst responses in the inferior colliculus were obtained at 6 months. Body weights of controls did not change over 6 months (approximately 32 g), but there was a significant (approximately 5 g) decline in the T1DM, while T2DM exhibited approximately 10 g weight gain. Blood glucose levels significantly increased: 3-fold for T1DM, 1.3-fold for T2DM; with no significant changes in controls. ABR threshold elevations were found for both types of diabetes, but were most pronounced in the T2DM, starting as early as 2 months after induction of diabetes. A decline of mean DPOAE amplitudes was observed in both diabetic groups at high frequencies, and for the T2DM at low frequencies. In contrast to ABR thresholds, tone and noise thresholds in the inferior colliculus were lower for both diabetic groups. Induction of diabetes in middle-aged CBA/CaJ mice promotes amplification of age-related peripheral hearing loss which makes it a suitable model for studying the interaction of age-related hearing loss and diabetes. On the other hand, initial results of effects from very high blood glucose level (T1DM) on the auditory midbrain showed disruption of central inhibition, increased response synchrony or enhanced excitation in the inferior colliculus. PMID:19271313

  11. Interactions of hearing loss and diabetes mellitus in the middle age CBA/CaJ mouse model of presbycusis.

    PubMed

    Vasilyeva, Olga N; Frisina, Susan T; Zhu, Xiaoxia; Walton, Joseph P; Frisina, Robert D

    2009-03-01

    Recently, we characterized the more severe nature of hearing loss in aged Type 2 diabetic human subjects [Frisina, S.T., Mapes, F., Kim, S., Frisina, D.R., Frisina, R.D., 2006. Characterization of hearing loss in aged type II diabetics. Hear. Res. 211, 103-113]. The current study prospectively assessed hearing abilities in middle age CBA/CaJ mice with Type 1 diabetes mellitus (T1DM) (STZ injection) or Type 2 diabetes mellitus (T2DM) (high fat diet), for a period of 6 months. Blood glucose, body weight and auditory tests (Auditory Brainstem Response-ABR, Distortion Product Otoacoustic Emissions-DPOAE) were evaluated at baseline and every 2 months. Tone and broad-band noise-burst responses in the inferior colliculus were obtained at 6 months. Body weights of controls did not change over 6 months (approximately 32 g), but there was a significant (approximately 5 g) decline in the T1DM, while T2DM exhibited approximately 10 g weight gain. Blood glucose levels significantly increased: 3-fold for T1DM, 1.3-fold for T2DM; with no significant changes in controls. ABR threshold elevations were found for both types of diabetes, but were most pronounced in the T2DM, starting as early as 2 months after induction of diabetes. A decline of mean DPOAE amplitudes was observed in both diabetic groups at high frequencies, and for the T2DM at low frequencies. In contrast to ABR thresholds, tone and noise thresholds in the inferior colliculus were lower for both diabetic groups. Induction of diabetes in middle-aged CBA/CaJ mice promotes amplification of age-related peripheral hearing loss which makes it a suitable model for studying the interaction of age-related hearing loss and diabetes. On the other hand, initial results of effects from very high blood glucose level (T1DM) on the auditory midbrain showed disruption of central inhibition, increased response synchrony or enhanced excitation in the inferior colliculus.

  12. Incidence of Type 1 Diabetes in Sweden Among Individuals Aged 0–34 Years, 1983–2007

    PubMed Central

    Dahlquist, Gisela G.; Nyström, Lennarth; Patterson, Christopher C.

    2011-01-01

    OBJECTIVE To clarify whether the increase in childhood type 1 diabetes is mirrored by a decrease in older age-groups, resulting in younger age at diagnosis. RESEARCH DESIGN AND METHODS We used data from two prospective research registers, the Swedish Childhood Diabetes Register, which included case subjects aged 0–14.9 years at diagnosis, and the Diabetes in Sweden Study, which included case subjects aged 15–34.9 years at diagnosis, covering birth cohorts between 1948 and 2007. The total database included 20,249 individuals with diabetes diagnosed between 1983 and 2007. Incidence rates over time were analyzed using Poisson regression models. RESULTS The overall yearly incidence rose to a peak of 42.3 per 100,000 person-years in male subjects aged 10–14 years and to a peak of 37.1 per 100,000 person-years in female subjects aged 5–9 years and decreased thereafter. There was a significant increase by calendar year in both sexes in the three age-groups <15 years; however, there were significant decreases in the older age-groups (25- to 29-years and 30- to 34-years age-groups). Poisson regression analyses showed that a cohort effect seemed to dominate over a time-period effect. CONCLUSIONS Twenty-five years of prospective nationwide incidence registration demonstrates a clear shift to younger age at onset rather than a uniform increase in incidence rates across all age-groups. The dominance of cohort effects over period effects suggests that exposures affecting young children may be responsible for the increasing incidence in the younger age-groups. PMID:21680725

  13. Hyperinsulinemia/diabetes, hearing, and aging in the University of Wisconsin calorie restriction monkeys.

    PubMed

    Fowler, Cynthia G; Chiasson, Kirstin Beach; Colman, Ricki J; Kemnitz, Joseph W; Beasley, T Mark; Weindruch, Richard H

    2015-10-01

    The purpose of this study was to determine the effects of hyperinsulinemia/Type 2 diabetes mellitus (HI-T2DM) on hearing impairment using rhesus monkeys to obtain control over diet and lifestyle factors that confound human studies. The study is a retrospective evaluation of rhesus monkeys from the Wisconsin National Primate Research Center (WNPRC) study on caloric restriction and aging. The research questions were the following: 1. Is HI-T2DM related to hearing impairment? 2. If so, what is the site of lesion in the auditory system? and 3. What physiological factors affect the risk of hearing loss in HI-T2DM? Three groups of eight monkeys each were matched by sex and age; the caloric restricted (CR) monkeys had a reduced risk of diabetes, the normal control (NL) group had a normal risk, and the hyperinsulinemia/diabetes (HI-D) group had already developed HI-T2DM. Auditory testing included distortion product otoacoustic emissions (DPOAEs) with f2 frequencies from 2211 to 8837 Hz and auditory brainstem responses (ABRs) obtained with clicks and tone bursts (8, 16, and 32 kHz). DPOAEs had signal-to-noise ratios 8-17 dB larger in the NL group than in the HI-D and CR groups, signifying that cochlear function was best in the NL group. ABR thresholds were 5-8 dB better in the NL group than in the HI-D group, although no significant differences across the groups were evident for the thresholds, latencies, interwave intervals, or amplitudes. Correlations were significant for quadratic relations between body mass index (BMI) and DPOAE, with largest DPOAEs for animals in the middle of the BMI range. ABR thresholds elicited with 16 and 32 kHz signals were significantly correlated, positively with BMI and HbA1c, and negatively with KG (glucose tolerance), SI (insulin sensitivity index) and DI (disposition index). These findings suggest that the hearing loss associated with HI-T2DM is predominantly cochlear, and auditory structures underlying the higher frequencies are at

  14. Hyperinsulinemia/diabetes, hearing, and aging in the University of Wisconsin calorie restriction monkeys.

    PubMed

    Fowler, Cynthia G; Chiasson, Kirstin Beach; Colman, Ricki J; Kemnitz, Joseph W; Beasley, T Mark; Weindruch, Richard H

    2015-10-01

    The purpose of this study was to determine the effects of hyperinsulinemia/Type 2 diabetes mellitus (HI-T2DM) on hearing impairment using rhesus monkeys to obtain control over diet and lifestyle factors that confound human studies. The study is a retrospective evaluation of rhesus monkeys from the Wisconsin National Primate Research Center (WNPRC) study on caloric restriction and aging. The research questions were the following: 1. Is HI-T2DM related to hearing impairment? 2. If so, what is the site of lesion in the auditory system? and 3. What physiological factors affect the risk of hearing loss in HI-T2DM? Three groups of eight monkeys each were matched by sex and age; the caloric restricted (CR) monkeys had a reduced risk of diabetes, the normal control (NL) group had a normal risk, and the hyperinsulinemia/diabetes (HI-D) group had already developed HI-T2DM. Auditory testing included distortion product otoacoustic emissions (DPOAEs) with f2 frequencies from 2211 to 8837 Hz and auditory brainstem responses (ABRs) obtained with clicks and tone bursts (8, 16, and 32 kHz). DPOAEs had signal-to-noise ratios 8-17 dB larger in the NL group than in the HI-D and CR groups, signifying that cochlear function was best in the NL group. ABR thresholds were 5-8 dB better in the NL group than in the HI-D group, although no significant differences across the groups were evident for the thresholds, latencies, interwave intervals, or amplitudes. Correlations were significant for quadratic relations between body mass index (BMI) and DPOAE, with largest DPOAEs for animals in the middle of the BMI range. ABR thresholds elicited with 16 and 32 kHz signals were significantly correlated, positively with BMI and HbA1c, and negatively with KG (glucose tolerance), SI (insulin sensitivity index) and DI (disposition index). These findings suggest that the hearing loss associated with HI-T2DM is predominantly cochlear, and auditory structures underlying the higher frequencies are at

  15. Age-Related Macular Degeneration: Advances in Management and Diagnosis

    PubMed Central

    Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

    2015-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

  16. Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns.

    PubMed

    Habes, M; Janowitz, D; Erus, G; Toledo, J B; Resnick, S M; Doshi, J; Van der Auwera, S; Wittfeld, K; Hegenscheid, K; Hosten, N; Biffar, R; Homuth, G; Völzke, H; Grabe, H J; Hoffmann, W; Davatzikos, C

    2016-01-01

    We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20-90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q<0.001). ABA patterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD. PMID:27045845

  17. Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns

    PubMed Central

    Habes, M; Janowitz, D; Erus, G; Toledo, J B; Resnick, S M; Doshi, J; Van der Auwera, S; Wittfeld, K; Hegenscheid, K; Hosten, N; Biffar, R; Homuth, G; Völzke, H; Grabe, H J; Hoffmann, W; Davatzikos, C

    2016-01-01

    We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20–90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q<0.001). ABA patterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD. PMID:27045845

  18. White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes

    PubMed Central

    Nunley, Karen A.; Ryan, Christopher M.; Orchard, Trevor J.; Aizenstein, Howard J.; Jennings, J. Richard; Ryan, John; Zgibor, Janice C.; Boudreau, Robert M.; Costacou, Tina; Maynard, John D.; Miller, Rachel G.

    2015-01-01

    Objective: Although microvascular complications are common in type 1 diabetes mellitus (T1DM), few studies have quantified the severity, risk factors, and implications of cerebral microvascular damage in these patients. As life expectancy in patients with T1DM increases, patients are exposed to age- and disease-related factors that may contribute to cerebral microvascular disease. Methods: Severity and volume of white matter hyperintensities (WMH) and infarcts were quantified in 97 middle-aged patients with childhood-onset T1DM (mean age and duration: 50 and 41 years, respectively) and 81 non-T1DM adults (mean age: 48 years), concurrent with cognitive and health-related measures. Results: Compared with non-T1DM participants, patients had more severe WMH (Fazekas scores 2 and 3 compared with Fazekas score 1, p < 0.0001) and slower information processing (digit symbol substitution, number correct: 65.7 ± 10.9 and 54.9 ± 13.6; pegboard, seconds: 66.0 ± 9.9 and 88.5 ± 34.2; both p < 0.0001) independent of age, education, or other factors. WMH were associated with slower information processing; adjusting for WMH attenuated the group differences in processing speed (13% for digit symbol, 11% for pegboard, both p ≤ 0.05). Among patients, prevalent neuropathies and smoking tripled the odds of high WMH burden, independent of age or disease duration. Associations between measures of blood pressure or hyperglycemia and WMH were not significant. Conclusions: Clinically relevant WMH are evident earlier among middle-aged patients with childhood-onset T1DM and are related to the slower information processing frequently observed in T1DM. Brain imaging in patients with T1DM who have cognitive difficulties, especially those with neuropathies, may help uncover cerebral microvascular damage. Longitudinal studies are warranted to fully characterize WMH development, risk factors, and long-term effects on cognition. PMID:25904692

  19. Characteristics of first-time fathers of advanced age: a Norwegian population-based study

    PubMed Central

    2013-01-01

    Background The modern phenomenon of delayed parenthood applies not only to women but also to men, but less is known about what characterises men who are expecting their first child at an advanced age. This study investigates the sociodemographic characteristics, health behaviour, health problems, social relationships and timing of pregnancy in older first-time fathers. Methods A cross-sectional study was conducted of 14 832 men who were expecting their first child, based on data from the Norwegian Mother and Child Cohort Study (MoBa) carried out by the Norwegian Institute of Public Health. Data were collected in 2005–2008 by means of a questionnaire in gestational week 17–18 of their partner’s pregnancy, and from the Norwegian Medical Birth Register. The distribution of background variables was investigated across the age span of 25 years and above. Men of advanced age (35–39 years) and very advanced age (40 years or more) were compared with men aged 25–34 years by means of bivariate and multivariate logistic regression analyses. Results The following factors were found to be associated with having the first child at an advanced or very advanced age: being unmarried or non-cohabitant, negative health behaviour (overweight, obesity, smoking, frequent alcohol intake), physical and mental health problems (lower back pain, cardiovascular diseases, high blood pressure, sleeping problems, previous depressive symptoms), few social contacts and dissatisfaction with partner relationship. There were mixed associations for socioeconomic status: several proxy measures of high socioeconomic status (e.g. income >65 000 €, self-employment) were associated with having the first child at an advanced or very advanced age, as were several other proxy measures of low socioeconomic status (e.g. unemployment, low level of education, immigrant background).The odds of the child being conceived after in vitro fertilisation were threefold in men aged 34–39 and fourfold from 40

  20. Advancing the Aging and Technology Agenda in Gerontology

    PubMed Central

    Schulz, Richard; Wahl, Hans-Werner; Matthews, Judith T.; De Vito Dabbs, Annette; Beach, Scott R.; Czaja, Sara J.

    2015-01-01

    Interest in technology for older adults is driven by multiple converging trends: the rapid pace of technological development; the unprecedented growth of the aging population in the United States and worldwide; the increase in the number and survival of persons with disability; the growing and unsustainable costs of caring for the elderly people; and the increasing interest on the part of business, industry, and government agencies in addressing health care needs with technology. These trends have contributed to the strong conviction that technology can play an important role in enhancing quality of life and independence of older individuals with high levels of efficiency, potentially reducing individual and societal costs of caring for the elderly people. The purpose of this “Forum” position article is to integrate what we know about older adults and technology systems in order to provide direction to this vital enterprise. We define what we mean by technology for an aging population, provide a brief history of its development, introduce a taxonomy for characterizing current technology applications to older adults, summarize research in this area, describe existing development and evaluation processes, identify factors important for the acceptance of technology among older individuals, and recommend future directions for research in this area. PMID:25165042

  1. Advancing the Aging and Technology Agenda in Gerontology.

    PubMed

    Schulz, Richard; Wahl, Hans-Werner; Matthews, Judith T; De Vito Dabbs, Annette; Beach, Scott R; Czaja, Sara J

    2015-10-01

    Interest in technology for older adults is driven by multiple converging trends: the rapid pace of technological development; the unprecedented growth of the aging population in the United States and worldwide; the increase in the number and survival of persons with disability; the growing and unsustainable costs of caring for the elderly people; and the increasing interest on the part of business, industry, and government agencies in addressing health care needs with technology. These trends have contributed to the strong conviction that technology can play an important role in enhancing quality of life and independence of older individuals with high levels of efficiency, potentially reducing individual and societal costs of caring for the elderly people. The purpose of this "Forum" position article is to integrate what we know about older adults and technology systems in order to provide direction to this vital enterprise. We define what we mean by technology for an aging population, provide a brief history of its development, introduce a taxonomy for characterizing current technology applications to older adults, summarize research in this area, describe existing development and evaluation processes, identify factors important for the acceptance of technology among older individuals, and recommend future directions for research in this area.

  2. A prospective observational study of quality of diabetes care in a shared care setting: trends and age differences (ZODIAC-19)

    PubMed Central

    van Hateren, Kornelis J J; Drion, Iefke; Kleefstra, Nanne; Groenier, Klaas H; Houweling, Sebastiaan T; van der Meer, Klaas; Bilo, Henk J G

    2012-01-01

    Objective The Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study was initiated in 1998 to investigate the effects of shared care for patients with type 2 diabetes mellitus (T2DM) in the Netherlands, and to reduce the number of diabetes-related complications. Benchmarking the performance of diabetes care was and is an important aspect of this study. We aimed to investigate trends in diabetes care, within the ZODIAC study for a wide variety of quality indicators during a long follow-up period (1998–2008), with special interest for different age groups. Design Prospective observational cohort study. Setting Primary care, Zwolle, The Netherlands. Participants Patients with T2DM. Methods A dataset of quality measures was collected annually during the patient's visit to the practice nurse or general practitioner. Linear time trends from 1998 to 2008 were estimated using linear mixed models in which we adjusted for age and gender. Age was included in the model as a categorical variable: for each follow-up year all participants were categorised into the categories <60, 60–75 and >75 years. Differences in trends between the age categories were investigated by adding an interaction term to the model. Results The number of patients who were reported to participate increased in the period 1998–2008 from 1622 to 27 438. All quality indicators improved in this study, except for body mass index. The prevalence albuminuria decreased in an 11-year-period from 42% to 21%. No relevant differences between the trends for the three age categories were observed. During all years of follow-up, mean blood pressure and body mass index were the lowest and highest, respectively, in the group of patients <60 years (data not shown). Conclusions Quality of diabetes care within the Dutch ZODIAC study, a shared care project, has considerably improved in the period 1998–2008. There were no relevant differences between trends across various age categories

  3. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

    PubMed Central

    Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M.; Mahmoudi, Morteza; De Rooij, Felix W. M.; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

    2015-01-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs. PMID:26337083

  4. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans.

    PubMed

    Rahimi, Mehran; Vinciguerra, Manlio; Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M; Mahmoudi, Morteza; De Rooij, Felix W M; Sijbrands, Eric; Peppelenbosch, Maikel P; Rezaee, Farhad

    2015-10-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs.

  5. Effects of ageing and experimental diabetes on insulin-degrading enzyme expression in male rat tissues.

    PubMed

    Kochkina, Ekaterina G; Plesneva, Svetlana A; Vasilev, Dmitrii S; Zhuravin, Igor A; Turner, Anthony J; Nalivaeva, Natalia N

    2015-08-01

    Due to an increasing life expectancy in developing countries, cases of type 2 diabetes and Alzheimer's disease (AD) in the elderly are growing exponentially. Despite a causative link between diabetes and AD, general molecular mechanisms underlying pathogenesis of these disorders are still far from being understood. One of the factors leading to cell death and cognitive impairment characteristic of AD is accumulation in the brain of toxic aggregates of amyloid-β peptide (Aβ). In the normally functioning brain Aβ catabolism is regulated by a cohort of proteolytic enzymes including insulin-degrading enzyme (IDE) and their deficit with ageing can result in Aβ accumulation and increased risk of AD. The aim of this study was a comparative analysis of IDE expression in the brain structures involved in AD, as well as in peripheral organs (the liver and kidney) of rats, during natural ageing and after experimentally-induced diabetes. It was found that ageing is accompanied by a significant decrease of IDE mRNA and protein content in the liver (by 32 and 81%) and brain structures (in the cortex by 58 and 47% and in the striatum by 53 and 68%, respectively). In diabetic animals, IDE protein level was increased in the liver (by 36%) and in the striatum (by 42%) while in the brain cortex and hippocampus it was 20-30% lower than in control animals. No significant IDE protein changes were observed in the kidney of diabetic rats. These data testify that ageing and diabetes are accompanied by a deficit of IDE in the brain structures where accumulation of Aβ was reported in AD patients, which might be one of the factors predisposing to development of the sporadic form of AD in the elderly, and especially in diabetics.

  6. Diabetes

    MedlinePlus

    ... to develop type 2 diabetes later in life. Polycystic ovary syndrome Polycystic ovary syndrome (PCOS) is a condition that occurs when an imbalance ... to form on the ovaries. Women who have PCOS are at an increased risk of developing type ...

  7. The Effect of Adverse Housing and Neighborhood Conditions on the Development of Diabetes Mellitus among Middle-aged African Americans

    PubMed Central

    Schootman, Mario; Andresen, Elena M.; Wolinsky, Fredric D.; Malmstrom, Theodore K.; Miller, J. Philip; Yan, Yan; Miller, Douglas K.

    2015-01-01

    The authors examined the associations of observed neighborhood (block face) and housing conditions with the incidence of diabetes by using data from 644 subjects in the African-American Health Study (St. Louis area, Missouri). They also investigated five mediating pathways (health behavior, psychosocial, health status, access to medical care, and sociodemographic characteristics) if significant associations were identified. The external appearance of the block the subjects lived on and housing conditions were rated as excellent, good, fair, or poor. Subjects reported about neighborhood desirability. Self-reported diabetes was obtained at baseline and 3 years later. Of 644 subjects without self-reported diabetes, 10.3% reported having diabetes at the 3-year follow-up. Every housing condition rated as fair-poor was associated with an increased risk of diabetes, with odds ratios ranging from 2.53 (95% confidence interval: 1.47, 4.34 for physical condition inside the building) to 1.78 (95% confidence interval: 1.03, 3.07 for cleanliness inside the building) in unadjusted analyses. No association was found between any of the block face conditions or perceived neighborhood conditions and incident diabetes. The odds ratios for the five housing conditions were unaffected when adjusted for the mediating pathways. Poor housing conditions appear to be an independent contributor to the risk of incident diabetes in urban, middle-aged African Americans. PMID:17625220

  8. Habitual sugar intake and cognitive function among middle-aged and older Puerto Ricans without diabetes.

    PubMed

    Ye, Xingwang; Gao, Xiang; Scott, Tammy; Tucker, Katherine L

    2011-11-01

    Intake of added sugars, mainly fructose and sucrose, has been associated with risk factors for cognitive impairment, such as obesity, the metabolic syndrome and type 2 diabetes. The objective of this analysis was to examine whether habitual intakes of total sugars, added sugars, sugar-sweetened beverages or sweetened solid foods are associated with cognitive function. The present study included 737 participants without diabetes, aged 45-75 years, from the Boston Puerto Rican Health Study, 2004-9. Cognitive function was measured with a battery of seven tests: Mini-Mental State Examination (MMSE), word list learning, digit span, clock drawing, figure copying, and Stroop and verbal fluency tests. Usual dietary intake was assessed with a validated FFQ. Greater intakes of total sugars, added sugars and sugar-sweetened beverages, but not of sugar-sweetened solid foods, were significantly associated with lower MMSE score, after adjusting for covariates. Adjusted OR for cognitive impairment (MMSE score < 24) were 2.23 (95 % CI 1.24, 3.99) for total sugars and 2.28 (95 % CI 1.26, 4.14) for added sugars, comparing the highest with lowest intake quintiles. Greater intake of total sugars was also significantly associated with lower word list learning score. In conclusion, higher sugar intake appears to be associated with lower cognitive function, but longitudinal studies are needed to clarify the direction of causality.

  9. Fetuin-A and Incident Diabetes Mellitus in Older Persons: The Health Aging and Body Composition (Health ABC) Study

    PubMed Central

    Ix, Joachim H.; Wassel-Fyr, Christina; Kanaya, Alka; Vittinghoff, Eric; Johnson, Karen C.; Koster, Annemarie; Cauley, Jane A.; Harris, Tamara B.; Cummings, Steven R.; Shlipak, Michael G.

    2009-01-01

    Context Fetuin-A is a hepatic secretory protein that binds the insulin receptor in muscle and fat and inhibits insulin action, in vitro. In prior cross-sectional studies in humans, higher fetuin-A was associated with insulin resistance. However, the longitudinal association of fetuin-A with incident diabetes mellitus is unknown. Objective To determine whether fetuin-A levels are associated with incident diabetes in older persons Design, Setting, and Participants Observational study among 3,075 well-functioning persons aged 70 to 79 years. In this case-cohort study, we retrospectively measured fetuin-A in baseline serum among 406 randomly selected participants without prevalent diabetes, and all participants who developed incident diabetes during 6-years of follow-up. Main Outcome Measure Incident diabetes mellitus. Results Incident diabetes developed in 135 participants (10.1 cases/1,000 person-years) over 6-years. Participants with fetuin-A levels within the highest tertile (>0.97 g/L) had more than two times higher risk of incident diabetes (adjusted Hazard Ratio [HR] 2.41; 95% Confidence Interval [CI] 1.28–4.53; P<0.01) compared to subjects in the lowest tertile (≤0.76 g/L) in models adjusted for age, sex, race, waist circumference, body weight, physical activity, blood pressure, fasting glucose, HDL cholesterol, triglycerides, and CRP levels. The association was not affected by adipocytokine levels, but was moderately attenuated by adjustment for visceral adiposity (adjusted HR of highest vs. lowest tertile 1.72; 95% CI 0.98–3.05; P=0.06). Conclusions Among well functioning older persons, serum fetuin-A is a novel risk factor for incident diabetes that is independent of markers of insulin resistance commonly available in clinical practice, and may be partially mediated through visceral adiposity. PMID:18612115

  10. The role of collagen crosslinks in ageing and diabetes - the good, the bad, and the ugly

    PubMed Central

    Snedeker, Jess G.; Gautieri, Alfonso

    2014-01-01

    Summary The non-enzymatic reaction of proteins with glucose (glycation) is a topic of rapidly growing importance in human health and medicine. There is increasing evidence that this reaction plays a central role in ageing and disease of connective tissues. Of particular interest are changes in type-I collagens, long-lived proteins that form the mechanical backbone of connective tissues in nearly every human organ. Despite considerable correlative evidence relating extracellular matrix (ECM) glycation to disease, little is known of how ECM modification by glucose impacts matrix mechanics and damage, cell-matrix interactions, and matrix turnover during aging. More daunting is to understand how these factors interact to cumulatively affect local repair of matrix damage, progression of tissue disease, or systemic health and longevity. This focused review will summarize what is currently known regarding collagen glycation as a potential driver of connective tissue disease. We concentrate attention on tendon as an affected connective tissue with large clinical relevance, and as a tissue that can serve as a useful model tissue for investigation into glycation as a potentially critical player in tissue fibrosis related to ageing and diabetes. PMID:25489547

  11. Impact of the advances in age on the gastrointestinal microflora of beagle dogs.

    PubMed

    Benno, Y; Nakao, H; Uchida, K; Mitsuoka, T

    1992-08-01

    The gastrointestinal microflora of male beagle dogs in two different age groups; I) less than month 12 of age, and II) more than year 11 of age, was compared. No detectable difference occurred on the microflora of stomach, duodenum, jejunum, and ileum in both dogs. Large bowel (cecum, colon and rectum) microflora in both dogs yielded the different microbial populations. In all regions of large bowel, the levels of bacteroides, eubacteria, peptostreptococci, bifidobacteria, lactobacilli, and staphylococci in the elderly dogs were lower than those in the younger animals, whereas the numbers of Clostridium perfringens and streptococci in the elderly animals were higher than those in the youngers. The high incidence of lecithinase-negative clostridia was observed with advances in age, but not that of spiral shaped rods. The result of this study shows that the advances in age of beagle dogs yield some changes in the microbial population of large bowel in the animals.

  12. State of Health and Quality of Life of Women at Advanced Age.

    PubMed

    Pinkas, Jarosław; Gujski, Mariusz; Humeniuk, Ewa; Raczkiewicz, Dorota; Bejga, Przemysław; Owoc, Alfred; Bojar, Iwona

    2016-01-01

    BACKGROUND Evaluation of the state of health, quality of life, and relationship between the level of the quality of life and health status in a group of women at advanced age (90 and more years) in Poland. MATERIAL AND METHODS The study was conducted in 2014 in an all-Polish sample of 870 women aged 90 and over. The research instruments were: the author's questionnaire, and standardized tests: Katz index of independence in Activities of Daily Living (ADL), Abbreviated Mental Test Score (AMTS), The World Health Organization Quality of Life (WHOQOL) - BREF. The results of the study were statistically analyzed using significant t test for mean and regression analysis. RESULTS The majority of women at advanced age suffered from chronic pain (76%) and such major geriatric problems as hypoacusis (81%), visual disturbances (69%) and urinary incontinence (60%), the minority - fall and fainting (39%) as well as stool incontinence (17%), severe functional and cognitive impairment (24% and 10% respectively). Women at advanced age assessed positively for overall quality of life (mean 3.3 on 1-5 scale), social relationships (3.5) and environment (3.2), but negatively - general, physical and psychological health (2.7, 2.7 and 2.8 respectively). The presence of chronic pain and major geriatric problems: urinary and stool incontinences, falls and fainting, visual disturbances and hypoacusis significantly decreases overall quality of life, general, physical and psychological health, social relationships and environment of women at advanced age. Overall quality of life, general, physical and psychological health, social relationships and environment correlate to functional and cognitive impairments of women at advanced age. CONCLUSIONS Quality of life of women at advanced age decreased if chronic pain, major geriatric problems as well as functional and cognitive impairments occur. PMID:27580565

  13. Influence of neighbourhood socioeconomic position on the transition to type II diabetes in older Mexican Americans: the Sacramento Area Longitudinal Study on Aging

    PubMed Central

    Garcia, Lorena; Lee, Anne; Zeki Al Hazzouri, Adina; Neuhaus, John M; Aiello, Allison; Elfassy, Tali; Haan, Mary N

    2016-01-01

    Objective To examine the influence of neighbourhood socioeconomic position (NSEP) on development of diabetes over time. Design A longitudinal cohort study. Setting The data reported were from the Sacramento Area Latino Study on Aging, a longitudinal study of the health of 1789 older Latinos. Participants Community-dwelling older Mexican Americans residing in the Sacramento Metropolitan Statistical Area. Main outcome Multistate Markov regression were used to model transitions through four possible states over time: 1=normal; 2=pre-diabetic; 3=diabetic; and 4=death without diabetes. Results At baseline, nearly 50% were non-diabetic, 17.5% were pre-diabetic and nearly 33% were diabetic. At the end of follow-up, there were a total of 824 people with type 2 diabetes. In a fully adjusted MSM regression model, among non-diabetics, higher NSEP was not associated with a transition to pre-diabetes. Among non-diabetics, higher NSEP was associated with an increased risk of diabetes (HR=1.66, 95% CI 1.14 to 2.42) and decreased risk of death without diabetes (HR: 0.56, 95% CI 0.33 to 0.96). Among pre-diabetics, higher NSEP was significantly associated with a transition to non-diabetic status (HR: 1.22, 95% CI 0.99 to 1.50). Adjusting for BMI, age, education, physical activity, smoking, alcohol consumption, medical insurance and nativity did not affect this relationship. Conclusions Our findings show that high NSEP poses higher risk of progression from normal to diabetes compared with a lower risk of death without diabetes. This work presents a possibility that these associations are modified by nativity or culture. PMID:27515749

  14. Susceptibility of Diabetic Rats to Pulmonary and Systemic Effects of Inhaled Photochemically-Aged Atmosphere and Ozone (O3)

    EPA Science Inventory

    Susceptibility of Diabetic Rats to Pulmonary and Systemic Effects of Inhaled Photochemically-Aged Atmosphere and Ozone (O3)MC Schladweiler1, SJ Snow2, QT Krantz1, C King1, JD Krug2, N Modak2, A Henriquez3, V Bass4, DJ Miller3, JE Richards1, EH Boykin1, R Jaskot1, MI Gilmour1 and ...

  15. Monograph series on aging-related diseases: VIII. Non-insulin-dependent diabetes mellitus (NIDDM)

    PubMed

    Barceló, A

    1996-01-01

    Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia and by disturbances of carbohydrate, fat and protein metabolism. Diabetes mellitus is associated with absolute or relative deficiency in the secretion and/or action of the hormone insulin.

  16. Mortality Measurement at Advanced Ages: A Study of the Social Security Administration Death Master File

    PubMed Central

    Gavrilov, Leonid A.; Gavrilova, Natalia S.

    2011-01-01

    Accurate estimates of mortality at advanced ages are essential to improving forecasts of mortality and the population size of the oldest old age group. However, estimation of hazard rates at extremely old ages poses serious challenges to researchers: (1) The observed mortality deceleration may be at least partially an artifact of mixing different birth cohorts with different mortality (heterogeneity effect); (2) standard assumptions of hazard rate estimates may be invalid when risk of death is extremely high at old ages and (3) ages of very old people may be exaggerated. One way of obtaining estimates of mortality at extreme ages is to pool together international records of persons surviving to extreme ages with subsequent efforts of strict age validation. This approach helps researchers to resolve the third of the above-mentioned problems but does not resolve the first two problems because of inevitable data heterogeneity when data for people belonging to different birth cohorts and countries are pooled together. In this paper we propose an alternative approach, which gives an opportunity to resolve the first two problems by compiling data for more homogeneous single-year birth cohorts with hazard rates measured at narrow (monthly) age intervals. Possible ways of resolving the third problem of hazard rate estimation are elaborated. This approach is based on data from the Social Security Administration Death Master File (DMF). Some birth cohorts covered by DMF could be studied by the method of extinct generations. Availability of month of birth and month of death information provides a unique opportunity to obtain hazard rate estimates for every month of age. Study of several single-year extinct birth cohorts shows that mortality trajectory at advanced ages follows the Gompertz law up to the ages 102–105 years without a noticeable deceleration. Earlier reports of mortality deceleration (deviation of mortality from the Gompertz law) at ages below 100 appear to be

  17. Cilostazol attenuates the severity of peripheral arterial occlusive disease in patients with type 2 diabetes: the role of plasma soluble receptor for advanced glycation end-products.

    PubMed

    Liu, Jhih-Syuan; Chuang, Tsung-Ju; Chen, Jui-Hung; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Lin, Tsung-Kun; Hsiao, Fone-Ching; Hung, Yi-Jen

    2015-08-01

    Recent studies have demonstrated that the plasma soluble receptor for advanced glycation end-products (sRAGE) play a major role in developing macrovascular complications of type 2 diabetes, including peripheral arterial occlusion disease (PAOD). Cilostazol is an antiplatelet, antithrombotic agent, which has been used for the treatment of PAOD. We hypothesized that cilostazol attenuates the severity of PAOD in patients with type 2 diabetes through the augmentation of plasma sRAGE. Ninety type 2 diabetic patients with PAOD defined as intermittent claudication with ankle-brachial index (ABI) ≦0.9 were recruited for an open-labeled, placebo-controlled study for 52 weeks with oral cilostazol 100 mg twice daily (n = 45) or placebo (n = 45). Fasting plasma sRAGE, endothelial variables of E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), and inflammatory markers of high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF-α) were determined. After completely the 52-week treatment program, the ABI values were elevated in cilostazol group (P < 0.001). The plasma sRAGE was significantly increased (P = 0.007), and hsCRP, sVCAM, and E-selectin concentrations were significantly decreased (P = 0.028, <0.001 and <0.001, respectively) with cilostazol treatment. In a partial correlation analysis with adjustments for sex and age, the net change of sRAGE significantly correlated with the change of ABI in the cilostazol group (P = 0.043). In a stepwise multiple regression model, only the change with regards to sRAGE was significantly associated with the change of ABI (P = 0.046). Our results suggest that cilostazol may effectively attenuate the severity of PAOD in patients with type 2 diabetes. Plasma sRAGE plays a role as an independent predictor for improving the index of PAOD.

  18. Cilostazol attenuates the severity of peripheral arterial occlusive disease in patients with type 2 diabetes: the role of plasma soluble receptor for advanced glycation end-products.

    PubMed

    Liu, Jhih-Syuan; Chuang, Tsung-Ju; Chen, Jui-Hung; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Lin, Tsung-Kun; Hsiao, Fone-Ching; Hung, Yi-Jen

    2015-08-01

    Recent studies have demonstrated that the plasma soluble receptor for advanced glycation end-products (sRAGE) play a major role in developing macrovascular complications of type 2 diabetes, including peripheral arterial occlusion disease (PAOD). Cilostazol is an antiplatelet, antithrombotic agent, which has been used for the treatment of PAOD. We hypothesized that cilostazol attenuates the severity of PAOD in patients with type 2 diabetes through the augmentation of plasma sRAGE. Ninety type 2 diabetic patients with PAOD defined as intermittent claudication with ankle-brachial index (ABI) ≦0.9 were recruited for an open-labeled, placebo-controlled study for 52 weeks with oral cilostazol 100 mg twice daily (n = 45) or placebo (n = 45). Fasting plasma sRAGE, endothelial variables of E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), and inflammatory markers of high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF-α) were determined. After completely the 52-week treatment program, the ABI values were elevated in cilostazol group (P < 0.001). The plasma sRAGE was significantly increased (P = 0.007), and hsCRP, sVCAM, and E-selectin concentrations were significantly decreased (P = 0.028, <0.001 and <0.001, respectively) with cilostazol treatment. In a partial correlation analysis with adjustments for sex and age, the net change of sRAGE significantly correlated with the change of ABI in the cilostazol group (P = 0.043). In a stepwise multiple regression model, only the change with regards to sRAGE was significantly associated with the change of ABI (P = 0.046). Our results suggest that cilostazol may effectively attenuate the severity of PAOD in patients with type 2 diabetes. Plasma sRAGE plays a role as an independent predictor for improving the index of PAOD. PMID:25666934

  19. [ADVANCE-ON Trial; How to Achieve Maximum Reduction of Mortality in Patients With Type 2 Diabetes].

    PubMed

    Kanorskiĭ, S G

    2015-01-01

    Of 10,261 patients with type 2 diabetes who survived to the end of a randomized ADVANCE trial 83% were included in the ADVANCE-ON project for observation for 6 years. The difference in the level of blood pressure which had been achieved during 4.5 years of within trial treatment with fixed perindopril/indapamide combination quickly vanished but significant decrease of total and cardiovascular mortality in the group of patients treated with this combination for 4.5 years was sustained during 6 years of post-trial follow-up. The results can be related to gradually weakening protective effect of perindopril/indapamide combination on cardiovascular system, and are indicative of the expedience of long-term use of this antihypertensive therapy for maximal lowering of mortality of patients with diabetes. PMID:26164995

  20. Contact allergy to topical medicaments becomes more common with advancing age: an age-stratified study.

    PubMed

    Green, Carl M; Holden, Catherine R; Gawkrodger, David J

    2007-04-01

    Eczema is common in the elderly people who often use topical medicaments. Previous studies in the elderly people have noted allergic positive patch tests in between 43% and 64% of those tested. We set out to assess whether medicament contact allergies are more common in elderly patients. We undertook a retrospective age-stratified study of all patients patch tested at the Royal Hallamshire Hospital, Sheffield, between January 1994 and July 2005. We confirmed that contact allergy to topical medicaments is more common in those aged more than 70 years compared with the younger age groups. There was no sex difference. The commonest problematic allergen types found in medicaments were fragrances and preservatives. The most frequent individual allergens were fragrance mix, Myroxylon pereirae, lanolins, local anaesthetic agents, neomycin and gentamicin, and tixocortol pivolate. The pattern of medicament contact allergens was similar to that of the younger age groups except that multiple allergic positives were more frequent and sensitivities to local anaesthetics and Myroxylon pereirae were proportionally more common. Elderly patients were more likely to have multiple contact allergies than the younger ones. Care needs to be taken when prescribing topical medicaments to elderly patients with eczema, especially for preparations that contain perfumes, lanolins, and local anaesthetics.

  1. Pharmacologic management of types 1 and 2 diabetes mellitus and their complications in women of childbearing age.

    PubMed

    Mukherjee, Mimi S; Coppenrath, Valerie A; Dallinga, Bree A

    2015-02-01

    The numbers of women of childbearing age with pregestational diabetes mellitus (diabetes existing before pregnancy) are increasing, primarily because more patients are developing type 2 diabetes at younger ages. The teratogenicity associated with hyperglycemia in early pregnancy is well documented, and tight glucose control minimizes the risk of congenital malformation. Preconception planning is essential; thus contraception that does not worsen complications of diabetes is desirable. In addition, because contraceptives are not 100% effective, the treatment of elevated blood glucose levels, hypertension, and dyslipidemia in these women requires consideration of unplanned pregnancy. We summarized the literature to aid clinicians in choosing individualized treatment that minimizes risk in case pregnancy occurs and maximizes benefit in preventing the complications of diabetes. In women with well-controlled diabetes without vascular disease, all contraceptive methods are safe. Intrauterine devices are recommended due to their minimal effects on risk factors for diabetic complications and their lack of reliance on patient adherence for efficacy. Among insulins, the insulin analogs-insulin lispro, insulin aspart, and insulin detemir-offer patients greater convenience than regular insulin and NPH insulin, and they are safe in case of unplanned pregnancy. Of the noninsulin agents, glyburide and metformin are the safest during pregnancy, but many of the other agents pose minimal risk as long as they are withdrawn during early pregnancy. The risks and benefits of angiotensin-converting enzyme inhibitors in women with compelling indications must be weighed individually. In hypertensive patients at a high risk for unplanned pregnancy, nifedipine should be considered due to literature supporting its safety during early pregnancy. Pravastatin is recommended for women with dyslipidemia who are using effective contraception because there have been no reports of birth defects with

  2. State of Health and Quality of Life of Women at Advanced Age

    PubMed Central

    Pinkas, Jarosław; Gujski, Mariusz; Humeniuk, Ewa; Raczkiewicz, Dorota; Bejga, Przemysław; Owoc, Alfred; Bojar, Iwona

    2016-01-01

    Background Evaluation of the state of health, quality of life, and the relationship between the level of the quality of life and health status in a group of women at an advanced age (90 years of age and older) in Poland. Material/Methods The study was conducted in 2014 in an all-Polish sample of 870 women aged 90 years and older. The research instruments were: the authors’ questionnaire and several standardized tests: Katz Index of Independence in Activities of Daily Living (Katz ADL), Abbreviated Mental Test Score (AMTS), and the World Health Organization Quality of Life (WHOQOL)-BREF. The results of the study were statistically analyzed using significant t-test for mean and regression analysis. Results The majority of women at an advanced age suffered from chronic pain (76%) and major geriatric problems such as hypoacusis (81%), visual disturbances (69%) and urinary incontinence (60%); the minority of women at an advanced age suffered from falls and fainting (39%), stool incontinence (17%), severe functional impairment (24%), and cognitive impairment (10%). On a scale of 1 to 5, women at an advanced age assessed positively for overall quality of life (mean 3.3), social relationships (3.5), and environment (3.2), but negatively for general health, physical health, and psychological health (2.7, 2.7, and 2.8, respectively). The presence of chronic pain and geriatric problems, including urinary and stool incontinences, falls and faint ing, visual disturbances and hypoacusis, significantly decreased overall quality of life; general health, physical health, psychological health, social relationships, and environment. Overall quality of life, general health, physical health, psychological health, social relationships, and environment was correlated with functional and cognitive impairments. Conclusions Quality of life of women at an advanced age decreased if chronic pain, major geriatric problems, or functional or cognitive impairments occurred. PMID:27580565

  3. The Benefits, Limitations, and Cost-Effectiveness of Advanced Technologies in the Management of Patients With Diabetes Mellitus

    PubMed Central

    Vigersky, Robert A.

    2015-01-01

    Background: Hypoglycemia mitigation is critical for appropriately managing patients with diabetes. Advanced technologies are becoming more prevalent in diabetes management, but their benefits have been primarily judged on the basis of hemoglobin A1c. A critical appraisal of the effectiveness and limitations of advanced technologies in reducing both A1c and hypoglycemia rates has not been previously performed. Methods: The cost of hypoglycemia was estimated using literature rates of hypoglycemia events resulting in hospitalizations. A literature search was conducted on the effect on A1c and hypoglycemia of advanced technologies. The cost-effectiveness of continuous subcutaneous insulin infusion (CSII) and real-time continuous glucose monitors (RT-CGM) was reviewed. Results: Severe hypoglycemia in insulin-using patients with diabetes costs $4.9-$12.7 billion. CSII reduces A1c in some but not all studies. CSII improves hypoglycemia in patients with high baseline rates. Bolus calculators improve A1c and improve the fear of hypoglycemia but not hypoglycemia rates. RT-CGM alone and when combined with CSII improve A1c with a neutral effect on hypoglycemia rates. Low-glucose threshold suspend systems reduce hypoglycemia with a neutral effect on A1c, and low-glucose predictive suspend systems reduce hypoglycemia with a small increase in plasma glucose levels. In short-term studies, artificial pancreas systems reduce both hypoglycemia rates and plasma glucose levels. CSII and RT-CGM are cost-effective technologies, but their wide adoption is limited by cost, psychosocial, and educational factors. Conclusions: Most currently available technologies improve A1c with a neutral or improved rate of hypoglycemia. Advanced technologies appear to be cost-effective in diabetes management, especially when including the underlying cost of hypoglycemia. PMID:25555391

  4. Suggested mechanism for the selective excretion of glucosylated albumin. The effects of diabetes mellitus and aging on this process and the origins of diabetic microalbuminuria.

    PubMed

    Kowluru, A; Kowluru, R; Bitensky, M W; Corwin, E J; Solomon, S S; Johnson, J D

    1987-11-01

    In previous studies in the Sprague-Dawley rat, Williams and coworkers reported the phenomenon of selective urinary excretion of glucosylated albumin (editing, i.e., the percent glucosylation of urinary albumin is more than that of plasma albumin) by the mammalian kidney. Ghiggeri and coworkers subsequently found that the extent of editing is reduced in human diabetics. Moreover, the reduction in editing in diabetes correlates inversely with levels of microalbuminuria. We also find reduction in the extent of editing in diabetic humans. We find a striking inverse correlation not only with the magnitude of microalbuminuria but also with the extent of plasma albumin glucosylation. In contrast, we found little correlation between the reduction in editing and the duration of diabetes in human subjects. Stz induced diabetes in the Sprague-Dawley rat is associated with a striking and rapid reduction in editing which develops virtually with the same kinetics exhibited by the appearance of hyperglycemia. This loss of editing is rapidly reversed by daily administration of insulin but not by aldose reductase inhibitors. Mannitol infusion in anesthetized Wistar rats resulted in an increase in urine volume, GFR, and microalbuminuria, and was also accompanied by a marked reduction in editing. This reduction was rapidly reversed by a cessation of mannitol infusion. We propose here that glucosylated albumin (in contrast to unmodified albumin) is not reabsorbed by the proximal tubule, and thus, is preferentially excreted in the urine. We postulate that the increase in GFR which emerges as a consequence of increased plasma osmolality in diabetes mellitus delivers more albumin to the proximal tubule than can be reabsorbed. This results in a dilution of excreted glucosylated albumin molecules by excreted unmodified albumin, which appears as the early microscopic albuminuria of diabetes. Paradoxically, the fall in apparent editing is accompanied by an absolute increase in the total

  5. Mindful Sustainable Aging: Advancing a Comprehensive Approach to the Challenges and Opportunities of Old Age.

    PubMed

    Nilsson, Håkan; Bülow, Pia H; Kazemi, Ali

    2015-08-01

    The primary aim of this article is to present a new concept called mindful sustainable aging (MSA), which is informed by mindfulness practices that support the physical, the mental, and especially, the social and the existential dimensions of old life. The concept of MSA is discussed and compared with four influential psychosocial theories in the field of gerontology, i.e., activity theory, disengagement theory, successful aging theory and gerotranscendence theory. The article ends with reviewing research on how mindfulness practice can help to manage, diminish and/or improve a number of serious physical conditions that are common among older people. The potential of mindfulness when it comes to facilitating for older adults in their quest for spiritual and existential meaning is discussed extensively throughout the article.

  6. Mindful Sustainable Aging: Advancing a Comprehensive Approach to the Challenges and Opportunities of Old Age

    PubMed Central

    Nilsson, Håkan; Bülow, Pia H.; Kazemi, Ali

    2015-01-01

    The primary aim of this article is to present a new concept called mindful sustainable aging (MSA), which is informed by mindfulness practices that support the physical, the mental, and especially, the social and the existential dimensions of old life. The concept of MSA is discussed and compared with four influential psychosocial theories in the field of gerontology, i.e., activity theory, disengagement theory, successful aging theory and gerotranscendence theory. The article ends with reviewing research on how mindfulness practice can help to manage, diminish and/or improve a number of serious physical conditions that are common among older people. The potential of mindfulness when it comes to facilitating for older adults in their quest for spiritual and existential meaning is discussed extensively throughout the article. PMID:27247673

  7. Usefulness of Photodynamic Diagnosis and Therapy using Talaporfin Sodium for an Advanced-aged Patient with Inoperable Gastric Cancer (a secondary publication)

    PubMed Central

    Oinuma, Takeshi

    2014-01-01

    Background and aims: In Japan the rise in the average life expectancy has caused an increase in the proportion of the population who are classed as geriatric. Accordingly, the number of elderly people being treated for cancer is increasing concomitantly. However, with the increase in age, the numbers of prior complications also increase. This is especially so in the advanced-aged patients, defined in Japan as those over the age of 85. Such complications may be too high risk for radical surgery and a less invasive treatment is warranted. Photodynamic therapy (PDT) is a noninvasive treatment approved by the Japanese National Health Insurance for the treatment of early stage superficial type esophageal and gastric cancers, early stage uterine cervical cancers and dysplasia, and early and advanced lung cancer. We report herein on the efficacy of palliative PDT using talaporfin sodium (Laserphyrin®) for a case of inoperable gastric cancer. Material and methods: The patient was an 87-year-old-man, a diabetic with histories of diabetic nephropathy, cerebral infarction and myocardial infarction. This patient was first diagnosed as having gastric cancer in 2007 but surgery and chemotherapy were contraindicated due to his poor physical status and poor renal function, respectively, owing to the anticipated side effects. The patient was referred to our institution after hearing of PDT in 2009. He was treated with 1 course of porfimer sodium PDT and 3 courses of talaporfin sodium PDT with photodynamic diagnosis (PDD) during the period from September, 2009 to June, 2011. Results: The massive gastric cancer located in the cardia was successfully treated with 4 PDT sessions without any serious complications; therefore the patient was able to orally ingest food until his death due to natural causes other than the cancer, in October, 2011. Conclusion: Talaporfin sodium PDT is safe and effective treatment for advanced-aged patients suffering from inoperable gastric cancer. PMID

  8. Lifestyle, nutrient intake, iron status, and pregnancy outcome in pregnant women of advanced maternal age.

    PubMed

    Bae, Hyun Sook

    2011-02-01

    The purpose of this study was to investigate how advanced maternal age influences lifestyle, nutrient intake, iron status, and pregnancy outcomes in pregnant women. The subjects of this study were 112 pregnant women who were receiving prenatal care at gynecologists located in Seoul. The subjects were divided into two groups according to their ages: those over age 35 were the advanced age group of pregnant women (AP) and those under age 35 were the young age group of pregnant women (YP). General factors, nutrient intakes, iron status, and pregnancy outcomes of the two groups were then compared. It was found that 72.5% of the YP group and 51.2% of the AP group had pre-pregnancy alcohol drinking experience; indicating that the YP group had more pre-pregnancy alcohol consumption than the AP group (P < 0.05). The only difference found in nutrient intake between the two groups was their niacin intakes which were 16.83 ± 8.20 mg/day and 13.76 ± 5.28 mg/day, respectively. When gestational age was shorter than 38.7 weeks, the average infant birth weight was 2.95 ± 0.08 kg, and when gestational age was longer than 40 weeks, it averaged at about 3.42 ± 0.08 kg. In other words, as gestational age increased, infant birth weight increased (P < 0.0001), and when maternal weight increased more than 15 kg, the infant birth weight increased significantly (P < 0.05). In conclusion, in order to secure healthy human resources, with respect to advanced aged women, it is necessary to intervene by promoting daily habits that consist of strategic increases in folate and calcium intake along with appropriate amounts of exercise.

  9. Surface exposure dating of Little Ice Age ice cap advances on Disko Island, West Greenland

    NASA Astrophysics Data System (ADS)

    Lane, Timothy; Jomelli, Vincent; Rinterknecht, Vincent; Brunstein, Daniel; Schimmelpfennig, Irene; Swingedouw, Didier; Favier, Vincent; Masson-Delmotte, Valerie

    2015-04-01

    Little Ice Age (LIA: 1200-1920 AD) glacier advances in Greenland often form the most extensive positions of Greenland Ice Sheet (GrIS) ice cap and margins since the Early Holocene. Across Greenland these advances are commonly represented by un-vegetated moraines, usually within 1-5 km of the present ice margin. However, chronological constraints on glacier advances during this period are sparse, meaning that GrIS and ice cap behavior and advance/retreat chronology remains poorly understood during this period. At present the majority of ages are based on historical accounts, ice core data, and radiocarbon ages from proglacial threshold lakes. However, developments in the accuracy and precision of surface exposure methods allow dating of LIA moraine boulders, permitting an opportunity to better understand of ice dynamics during this period. Geomorphological mapping and surface exposure dating (36Cl) were used to interpret moraine deposits from the Lyngmarksbræen on Disko Island, West Greenland. A Positive Degree Day (PDD) model was used to estimate Equilibrium Line Altitude (ELA) and mass balance changes for two distinct paleo-glacial extents. Three moraines (M1, M2, and M3) were mapped in the field, and sampled for 36Cl surface exposure dating. The outermost moraine (M1) was of clearly different morphology to the inner moraines, and present only in small fragments. M2 and M3 were distinct arcuate termino-lateral moraines within 50 m of one another, 1.5 km from the present ice margin. The weighted average of four 36Cl ages from M1 returned an early Holocene age of 8.4 ± 0.6 ka. M2 (four samples) returned an age of 0.57 ± 0.04 ka (1441 AD) and M3 (four samples) returned an age of 0.28 ± 0.02 ka (1732 AD). These surface exposure ages represent the first robustly dated Greenlandic ice cap moraine sequence from the LIA. The two periods of ice cap advance and marginal stabilisation are similar to recorded periods of LIA GrIS advance in west Greenland, constrained

  10. Cosmogenic 10Be constraints on Little Ice Age glacial advances in the eastern Tian Shan, China

    NASA Astrophysics Data System (ADS)

    Li, Yanan; Li, Yingkui; Harbor, Jon; Liu, Gengnian; Yi, Chaolu; Caffee, Marc W.

    2016-04-01

    Presumed Little Ice Age (LIA) glacial advances, represented by a set of fresh, sharp-crested, boulder covered and compact moraines a few hundred meters downstream from modern glaciers, have been widely recognized in the Central Asian highlands. However, few studies have constrained the formation ages of these moraines. We report 31 10Be exposure ages from presumed LIA moraines in six glacial valleys in the Urumqi River headwater area and the Haxilegen Pass area of the eastern Tian Shan, China. Our results reveal that the maximum LIA glacial extent occurred mainly around 430 ± 100 yr, a cold and wet period as indicated by proxy data from ice cores, tree rings, and lake sediments in Central Asia. We also dated a later glacial advance to 270 ± 55 yr. However, 10Be exposure ages on several presumed LIA moraines in front of small, thin glaciers are widely scattered and much older than the globally recognized timing of the LIA. Historical topographic maps indicate that most glaciers were more extensive in the early 1960s, and two of our 10Be sample sites were located close to the ice front at that time. Boulders transported by these small and thin glaciers may be reworked from deposits originally formed prior to the LIA glacial advances, producing apparently old and widely scattered exposure ages due to varied nuclide inheritance. Other published ages indicated an earlier LIA advance around 790 ± 300 yr in the easternmost Tian Shan, but in our study area the more extensive advance around 430 ± 100 yr likely reworked or covered deposits from this earlier event.

  11. Evaluation of the antioxidant and anti-glication effects of the hexane extract from Piper auritum leaves in vitro and beneficial activity on oxidative stress and advanced glycation end-product-mediated renal injury in streptozotocin-treated diabetic rats.

    PubMed

    Perez Gutierrez, Rosa Martha; Flores Cotera, Luis B; Gonzalez, Adriana Maria Neira

    2012-10-09

    The aim of this study was to investigate the antioxidant activity of hexane extracts from leaves of Piper auritum (HS). Eight complementary in vitro test methods were used, including inhibition of DPPH· radicals, nitric oxide, superoxide anion, ion-chelating, ABTS, oxygen radical absorbance capacity, β-carotene bleaching and peroxy radical scavenging. The results indicated that HS possesses high antioxidant activity. To add to these finding we tested the effect against oxidative stress in liver, pancreas and kidney in diabetic rats. Low levels of SOD, CAT, GPx and GSH in diabetic rats were reverted to near normal values after treatment with HS. These results suggest that P. auritum prevents oxidative stress, acting as a suppressor of liver cell damage. Given the link between glycation and oxidation, we proposed that HS might possess significant in vitro antiglycation activity. Our data confirmed the inhibitory effect of HS on bovine serum albumin, serum glycosylated protein, glycation of LDL, and glycation hemoglobin. The effect of HS on diabetic renal damage was investigated using streptozotocin-induced diabetic rats. The oral administration of HS at a dose of 200 and 400 mg/kg body weight/day for 28 days significantly reduced advanced glycation endproduct (AGE) formation, elevated renal glucose and thiobarbituric acid-reactive substance levels in the kidneys of diabetic rats. This implies that HS would alleviate the oxidative stress under diabetes through the inhibition of lipid peroxidation. These findings indicate that oxidative stress is increased in the diabetic rat kidney and that HS can prevent renal damage associated with diabetes by attenuating the oxidative stress.

  12. THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM

    EPA Science Inventory

    THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM (CHC13). A McDonald, Y M Sey and J E Simmons. NHEERL, ORD, U.S. EPA, RTP, NC.
    Disinfection, by chlorination or by ozonation followed by treatment with either chlorine or chloramine, of water containi...

  13. Advances in Disentangling Age, Cohort, and Time Effects: No Quadrature of the Circle, but a Help

    ERIC Educational Resources Information Center

    Masche, J. Gowert; van Dulmen, Manfred H. M.

    2004-01-01

    Based on Schaie's (1965) general developmental model, various data-driven and theory-based approaches to the exploration and disentangling of age, cohort, and time effects on human behavior have emerged. This paper presents and discusses an advancement of data-driven interpretations that stresses parsimony when interpreting the results of…

  14. Short term exercise induces PGC-1α, ameliorates inflammation and increases mitochondrial membrane proteins but fails to increase respiratory enzymes in aging diabetic hearts.

    PubMed

    Botta, Amy; Laher, Ismail; Beam, Julianne; Decoffe, Daniella; Brown, Kirsty; Halder, Swagata; Devlin, Angela; Gibson, Deanna L; Ghosh, Sanjoy

    2013-01-01

    PGC-1α, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1α is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1α on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1α without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFα) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1α such as NRF-1 and several respiratory genes. Such mismatch between PGC-1α and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1α expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1α mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age.

  15. Spousal support and food-related behavior change in middle-aged and older adults living with type 2 diabetes.

    PubMed

    Beverly, Elizabeth A; Miller, Carla K; Wray, Linda A

    2008-10-01

    One of the most challenging diabetes-related behavior changes is adhering to a healthful diet. Drawing on the social cognitive theory and social support literature, this qualitative study explores how spousal support influences dietary changes following a diagnosis of type 2 diabetes in middle-aged and older adults. The purpose of this study was to determine how aspects of the spousal relationship translate into behavior changes, specifically adherence to a healthful diet. Analyses revealed five core themes related to dietary adherence: control over food, dietary competence, commitment to support, spousal communication, and coping with diabetes. The themes can be categorized within two key social cognitive theory constructs: reinforcement and self-efficacy. Implications from the focus group data can inform the development of more effective, targeted nutrition messages and programs to provide specific knowledge and skills.

  16. Non-albuminuric renal disease among subjects with advanced stages of chronic kidney failure related to type 2 diabetes mellitus.

    PubMed

    Boronat, Mauro; García-Cantón, César; Quevedo, Virginia; Lorenzo, Dionisio L; López-Ríos, Laura; Batista, Fátima; Riaño, Marta; Saavedra, Pedro; Checa, María D

    2014-03-01

    Urinary albumin excretion has been consistently found to be normal in a significant number of subjects with early stages of diabetic kidney disease. This study was aimed to estimate the prevalence and characteristics of non-albuminuric chronic kidney disease associated with type 2 diabetes mellitus among subjects who reach advanced stages of renal failure. Study population was composed of incident patients with advanced chronic kidney disease (glomerular filtration rate <30 mL/min) related to type 2 diabetes in a tertiary hospital from Gran Canaria (Spain) during a period of 2 years. Subjects were classified as normoalbuminuric (urinary albumin-to-creatine ratio [UACR] <30 mg/g), microalbuminuric (UACR ≥30 and <300 mg/g), or proteinuric (UACR ≥300 mg/g). Of 78 eligible patients, 21.8% had normoalbuminuria, 20.5% had microalbuminuria, and 57.7% had proteinuria. Individuals with normoalbuminuria were mostly women and had a lower prevalence of smoking and polyneuropathy than subjects with microalbuminuria or proteinuria. They also presented greater measures of body mass index and waist circumference, higher values of total and LDL cholesterol, and lower values of HbA1c and serum creatinine than subjects with microalbuminuria or proteinuria. Multivariate analysis demonstrated that female sex (positively) and HbA1c and polyneuropathy (negatively) were independently associated with absence of albuminuria. In conclusion, around 20% of subjects with diabetes-related advanced chronic kidney disease, characteristically women, have normal urinary albumin excretion. HbA1c and polyneuropathy are inversely related to this non-albuminuric form of nephropathy.

  17. Chemical modification of proteins by lipids in diabetes.

    PubMed

    Baynes, John W

    2003-09-01

    Advanced glycation and lipoxidation end-products (AGE/ALE) increase in tissue proteins with age and at an accelerated rate in diabetes. This Review focuses on the nature and source of AGEs/ALEs and the factors affecting their formation in tissue and plasma proteins. Lipids are identified as an important source of chemical modification of proteins in diabetes, and the role of diabetes, dyslipidemia and renal disease in formation of AGEs/ALEs is reviewed. The article concludes with a discussion of ELISA assays for AGEs/ALEs and the merits of measuring AGEs/ALEs in the clinical laboratory.

  18. Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).

    PubMed

    Iyengar, Sudha K; Sedor, John R; Freedman, Barry I; Kao, W H Linda; Kretzler, Matthias; Keller, Benjamin J; Abboud, Hanna E; Adler, Sharon G; Best, Lyle G; Bowden, Donald W; Burlock, Allison; Chen, Yii-Der Ida; Cole, Shelley A; Comeau, Mary E; Curtis, Jeffrey M; Divers, Jasmin; Drechsler, Christiane; Duggirala, Ravi; Elston, Robert C; Guo, Xiuqing; Huang, Huateng; Hoffmann, Michael Marcus; Howard, Barbara V; Ipp, Eli; Kimmel, Paul L; Klag, Michael J; Knowler, William C; Kohn, Orly F; Leak, Tennille S; Leehey, David J; Li, Man; Malhotra, Alka; März, Winfried; Nair, Viji; Nelson, Robert G; Nicholas, Susanne B; O'Brien, Stephen J; Pahl, Madeleine V; Parekh, Rulan S; Pezzolesi, Marcus G; Rasooly, Rebekah S; Rotimi, Charles N; Rotter, Jerome I; Schelling, Jeffrey R; Seldin, Michael F; Shah, Vallabh O; Smiles, Adam M; Smith, Michael W; Taylor, Kent D; Thameem, Farook; Thornley-Brown, Denyse P; Truitt, Barbara J; Wanner, Christoph; Weil, E Jennifer; Winkler, Cheryl A; Zager, Philip G; Igo, Robert P; Hanson, Robert L; Langefeld, Carl D

    2015-08-01

    Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD. PMID:26305897

  19. Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).

    PubMed

    Iyengar, Sudha K; Sedor, John R; Freedman, Barry I; Kao, W H Linda; Kretzler, Matthias; Keller, Benjamin J; Abboud, Hanna E; Adler, Sharon G; Best, Lyle G; Bowden, Donald W; Burlock, Allison; Chen, Yii-Der Ida; Cole, Shelley A; Comeau, Mary E; Curtis, Jeffrey M; Divers, Jasmin; Drechsler, Christiane; Duggirala, Ravi; Elston, Robert C; Guo, Xiuqing; Huang, Huateng; Hoffmann, Michael Marcus; Howard, Barbara V; Ipp, Eli; Kimmel, Paul L; Klag, Michael J; Knowler, William C; Kohn, Orly F; Leak, Tennille S; Leehey, David J; Li, Man; Malhotra, Alka; März, Winfried; Nair, Viji; Nelson, Robert G; Nicholas, Susanne B; O'Brien, Stephen J; Pahl, Madeleine V; Parekh, Rulan S; Pezzolesi, Marcus G; Rasooly, Rebekah S; Rotimi, Charles N; Rotter, Jerome I; Schelling, Jeffrey R; Seldin, Michael F; Shah, Vallabh O; Smiles, Adam M; Smith, Michael W; Taylor, Kent D; Thameem, Farook; Thornley-Brown, Denyse P; Truitt, Barbara J; Wanner, Christoph; Weil, E Jennifer; Winkler, Cheryl A; Zager, Philip G; Igo, Robert P; Hanson, Robert L; Langefeld, Carl D

    2015-08-01

    Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.

  20. Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND)

    PubMed Central

    Kretzler, Matthias; Keller, Benjamin J.; Adler, Sharon G.; Best, Lyle G.; Bowden, Donald W.; Burlock, Allison; Chen, Yii-Der Ida; Cole, Shelley A.; Comeau, Mary E.; Curtis, Jeffrey M.; Divers, Jasmin; Drechsler, Christiane; Duggirala, Ravi; Elston, Robert C.; Guo, Xiuqing; Huang, Huateng; Hoffmann, Michael Marcus; Howard, Barbara V.; Ipp, Eli; Kimmel, Paul L.; Klag, Michael J.; Knowler, William C.; Kohn, Orly F.; Leak, Tennille S.; Leehey, David J.; Li, Man; Malhotra, Alka; März, Winfried; Nair, Viji; Nelson, Robert G.; Nicholas, Susanne B.; O’Brien, Stephen J.; Pahl, Madeleine V.; Parekh, Rulan S.; Pezzolesi, Marcus G.; Rasooly, Rebekah S.; Rotimi, Charles N.; Rotter, Jerome I.; Schelling, Jeffrey R.; Seldin, Michael F.; Shah, Vallabh O.; Smiles, Adam M.; Smith, Michael W.; Taylor, Kent D.; Thameem, Farook; Thornley-Brown, Denyse P.; Truitt, Barbara J.; Wanner, Christoph; Weil, E. Jennifer; Winkler, Cheryl A.; Zager, Philip G.; Igo, Robert P.; Hanson, Robert L.; Langefeld, Carl D.

    2015-01-01

    Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD. PMID:26305897

  1. Bone Turnover Does Not Reflect Skeletal Aging in Older Hispanic Men with Type 2 Diabetes

    NASA Technical Reports Server (NTRS)

    Rianon, N.; McCormick, J.; Ambrose, C.; Smith, S. M.; Fisher-Hoch, S.

    2016-01-01

    The paradox of fragility fracture in the presence of non-osteoporotic bone mineral density in older patients with type 2 diabetes mellitus (DM2) makes it difficult to clinically predict fracture in this vulnerable group. Serum osteocalcin (OC), a marker of bone turnover, increases with normal skeletal aging indicating risk of fracture. However, OC has been reported to be lower in patients with DM2. An inverse association between higher glycated hemoglobin levels (HbA1c) and lower serum OC in older DM2 patients triggered discussions encouraging further investigation. A key question to be answered is whether changes in glucose metabolism is responsible for bone metabolic changes, ultimately leading to increased risk of fragility fractures in DM2 patients. While these studies were conducted among Caucasian and Asian populations, this has not been studied in Hispanic populations who suffer from a higher prevalence of DM2. The Cameron County Hispanic Cohort (CCHC) in Texas is a homogeneous Hispanic cohort known to have high prevalence of DM2 (30%). Our preliminary data from this cohort reported OC levels lower than the suggested threshold for fragility fracture in post-menopausal women. We further investigated whether bone turnover in older CCHC adults with DM2 show a normal pattern of skeletal aging. Samples and data were obtained from a nested cohort of 68 (21 men and 47 women) Hispanic older adults (=50 years) who had a diagnosis of DM2. Given high prevalence of uncontrolled DM2 in this cohort, we divided population into two groups: i) poor DM2 control with HbA1c level =8 (48% men and 38% women) and ii) good DM2 control with HbA1c level <8). A crosssectional analysis documented associations between serum OC and age adjusted HbA1c levels. There was no direct association between age and OC concentrations in our study. Higher HbA1c was associated with lower serum OC in men (odds ratio -6.5, 95% confidence interval -12.7 to - 0.3, p < 0.04). No significant associations

  2. Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat.

    PubMed

    Son, Kuk Hui; Son, Myeongjoo; Ahn, Hyosang; Oh, Seyeon; Yum, Yoonji; Choi, Chang Hu; Park, Kook Yang; Byun, Kyunghee

    2016-08-19

    Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly.

  3. Android Adiposity and Lack of Moderate and Vigorous Physical Activity Are Associated With Insulin Resistance and Diabetes in Aging Adults

    PubMed Central

    Al Snih, Soham; Serra-Rexach, José A.; Burant, Charles

    2015-01-01

    Background. Physical inactivity and excess adiposity are thought to be interdependent “lifestyle” factors and thus, many older adults are at exaggerated risk for preventable diseases. The purposes of this study were to determine the degree of discordance between body mass index (BMI) and adiposity among adults older than 50 years, and to determine the extent to which direct measures of adiposity, and objectively measured sedentary behavior (SB) and physical activity (PA) are associated with insulin resistance (IR) or diabetes. Methods. A population representative sample of 2,816 individuals, aged 50–85 years, was included from the combined 2003–2006 National Health and Nutrition Examination Survey (NHANES) datasets. BMI, percent body fat (%BF) and android adiposity as determined by dual energy x-ray absorptiometry, objectively measured SB and PA, established markers of cardiometabolic risk, IR, and type 2 diabetes were analyzed. Results. Approximately 50% of the men and 64% of the women who were normal weight according to BMI had excessive %BF. Adults with the least SB and greatest moderate and vigorous PA exhibited the healthiest cardiometabolic profiles, whereas adults with the greatest SB and lowest activity had highest risk. Greater android adiposity stores were robustly associated with IR or diabetes in all adults, independent of SB and activity. Among men, less moderate-to-vigorous PA was associated with IR or diabetes; whereas among women, less lifestyle moderate activity was associated with IR or diabetes. Conclusions. Android adiposity and low moderate and vigorous PA are the strongest predictors of IR or diabetes among aging adults. PMID:25711528

  4. Burden of Hypertension and Diabetes among Urban Population Aged ≥ 60 years in South Delhi: A Community Based Study

    PubMed Central

    Goswami, Anil Kumar; Gupta, Sanjeev Kumar; Kalaivani, Mani; Pandav, Chandrakant S.

    2016-01-01

    Introduction India is going through a demographic transition, and the number of elderly is expected to increase both in absolute numbers, as well as in proportion. The elderly are one of the most vulnerable and high–risk group in terms of health status in any society, and more so for non- communicable diseases. Aims To estimate the prevalence of diabetes and hypertension among elderly persons and association with socio-demographic variables; & to assess the awareness, treatment and control status of those with diabetes and hypertension. Materials and Methods A cross-sectional community based study was carried out in a resettlement colony of South-east Delhi in Dakshinpuri Extension, Dr. Ambedkar Nagar. Elderly persons aged 60 years and above were selected by cluster random sampling. Information about self-reported diseases, socio-demographic variables was collected; fasting blood sugar and blood pressure were measured. Prevalence of diabetes and hypertension were calculated and association was tested by Chi-square test. Multivariate logistic regression analysis was used. Results A total of 710 elderly persons participated in the study. Diabetes was seen in 24.0% and 67% were hypertensive. Isolated hypertension was detected in 25.9%. No statistically significant difference by gender (p=0.11), age (p=0.16), education (p=0.31) and economic dependency (p=0.28), was seen in both diabetes and hypertension. Out of 167 persons with diabetes, 62.3% were on treatment and 33.6% were under control; while out of 477 hypertensives, 41% were under treatment and only one-third of them had their blood pressure under control. Conclusion This study highlighted a significant burden of non-communicable diseases amongst elderly persons in a low-middle class community in Delhi. It also showed the lack of awareness about their disease conditions and need for screening, diagnostic and treatment services at the primary level. PMID:27134900

  5. Neighborhood conditions, diabetes, and risk of lower-body functional limitations among middle-aged African Americans: A cohort study

    PubMed Central

    2010-01-01

    Background The relationship between presence of diabetes and adverse neighborhood and housing conditions and their effect on functional decline is unclear. We examined the association of adverse neighborhood (block face) and housing conditions with incidence of lower-body functional limitations among persons with and those without diabetes using a prospective population-based cohort study of 563 African Americans 49-65 years of age at their 2000-2001 baseline interviews. Methods Participants were randomly sampled African Americans living in the St. Louis area (response rate: 76%). Physician-diagnosed diabetes was self reported at baseline interview. Lower-body functional limitations were self reported based on the Nagi physical performance scale at baseline and the three-year follow-up interviews. The external appearance of the block the respondent lived on and five housing conditions were rated by study interviewers. All analyses were done using propensity score methods to control for confounders. Results 109 (19.4%) of subjects experienced incident lower-body functional limitations at three-year follow-up. In adjusted analysis, persons with diabetes who lived on block faces rated as fair-poor on each of the five conditions had higher odds (7.79 [95% confidence interval: 1.36-37.55] to 144.6 [95% confidence interval: 4.45-775.53]) of developing lower-body functional limitations than the referent group of persons without diabetes who lived on block faces rated as good-excellent. At least 80 percent of incident lower-body functional limitations was attributable to the interaction between block face conditions and diabetes status. Conclusions Adverse neighborhood conditions appear to exacerbate the detrimental effects on lower-body functioning associated with diabetes. PMID:20507573

  6. Implications of advancing paternal age: does it affect offspring school performance?

    PubMed

    Svensson, Anna C; Abel, Kathryn; Dalman, Christina; Magnusson, Cecilia

    2011-01-01

    Average paternal age is increasing in many high income countries, but the implications of this demographic shift for child health and welfare are poorly understood. There is equivocal evidence that children of older fathers are at increased risk of neurodevelopmental disorders and reduced IQ. We therefore report here on the relationship between paternal age and a composite indicator of scholastic achievement during adolescence, i.e. compulsory school leaving grades, among recent birth cohorts in Stockholm County where delayed paternity is notably common. We performed a record-linkage study comprising all individuals in Stockholm County who finished 9 years of compulsory school from 2000 through 2007 (n = 155,875). Data on school leaving grades and parental characteristics were retrieved from administrative and health service registers and analyzed using multiple linear regression. Advancing paternal age at birth was not associated with a decrease in school leaving grades in adolescent offspring. After adjustment for year of graduation, maternal age and parental education, country of birth and parental mental health service use, offspring of fathers aged 50 years or older had on average 0.3 (95% CI -3.8, 4.4) points higher grades than those of fathers aged 30-34 years. In conclusion, advancing paternal age is not associated with poorer school performance in adolescence. Adverse effects of delayed paternity on offspring cognitive function, if any, may be counterbalanced by other potential advantages for children born to older fathers.

  7. [Technological advances in the treatment of type 1 diabetes in pediatric patients].

    PubMed

    Tubiana-Rufi, N

    2013-12-01

    The most recent innovations serving pediatric type 1 diabetes patients are the insulin pump and its new functions and continuous glucose measurement, which, associated with the pump, foreshadows the artificial pancreas. Strictly controlling glycemia in type 1 diabetes is necessary to prevent complications, but the main side effect is the risk of frequent episodes of hypoglycemia, most particularly severe hypoglycemia.

  8. Mobile Applications for Diabetics: A Systematic Review and Expert-Based Usability Evaluation Considering the Special Requirements of Diabetes Patients Age 50 Years or Older

    PubMed Central

    Quade, Mandy; Kirch, Wilhelm

    2014-01-01

    Background A multitude of mhealth (mobile health) apps have been developed in recent years to support effective self-management of patients with diabetes mellitus type 1 or 2. Objective We carried out a systematic review of all currently available diabetes apps for the operating systems iOS and Android. We considered the number of newly released diabetes apps, range of functions, target user groups, languages, acquisition costs, user ratings, available interfaces, and the connection between acquisition costs and user ratings. Additionally, we examined whether the available applications serve the special needs of diabetes patients aged 50 or older by performing an expert-based usability evaluation. Methods We identified relevant keywords, comparative categories, and their specifications. Subsequently, we performed the app review based on the information given in the Google Play Store, the Apple App Store, and the apps themselves. In addition, we carried out an expert-based usability evaluation based on a representative 10% sample of diabetes apps. Results In total, we analyzed 656 apps finding that 355 (54.1%) offered just one function and 348 (53.0%) provided a documentation function. The dominating app language was English (85.4%, 560/656), patients represented the main user group (96.0%, 630/656), and the analysis of the costs revealed a trend toward free apps (53.7%, 352/656). The median price of paid apps was €1.90. The average user rating was 3.6 stars (maximum 5). Our analyses indicated no clear differences in the user rating between free and paid apps. Only 30 (4.6%) of the 656 available diabetes apps offered an interface to a measurement device. We evaluated 66 apps within the usability evaluation. On average, apps were rated best regarding the criterion “comprehensibility” (4.0 out of 5.0), while showing a lack of “fault tolerance” (2.8 out of 5.0). Of the 66 apps, 48 (72.7%) offered the ability to read the screen content aloud. The number of

  9. Rediscovering the classic osteopathic literature to advance contemporary patient-oriented research: A new look at diabetes mellitus

    PubMed Central

    Licciardone, John C

    2008-01-01

    Patient care experiences represent opportunities for establishing theories, testable hypotheses, and data to assess the potential use of osteopathic manipulative treatment in various disease conditions. The re-analysis of Bandeen's 1949 raw data described herein summarizes the effects of osteopathic manipulative treatment involving pancreatic stimulatory and inhibitory techniques in diabetic and non-diabetic patients seen over a 25-year period of clinical practice. Bandeen's data demonstrate a reduction in blood glucose levels at 30 and 60 minutes following pancreatic stimulation in 150 diabetic patients, and an elevation in blood glucose levels at 30 and 60 minutes following pancreatic inhibition in 40 non-diabetic patients. Such patient-oriented research conducted during the classic era of osteopathy in the United States provides a foundation and data for generating hypotheses about the potential mechanisms of action of osteopathic manipulative treatment. Osteopathic investigators would be well-served to rediscover the classic osteopathic literature to help advance contemporary evidence-based medicine. PMID:18644129

  10. Proactive gait strategies to mitigate risk of obstacle contact are more prevalent with advancing age.

    PubMed

    Muir, B C; Haddad, J M; Heijnen, M J H; Rietdyk, S

    2015-01-01

    The purposes of this study were to determine if healthy older adults adopt strategies to decrease the likelihood of obstacle contact, and to determine how these strategies are modified as a function of advancing age. Three age groups were examined: 20-25 yo (N = 19), 65-79 yo (N = 11), and 80-91 yo (N = 18). Participants stepped over a stationary, visible obstacle on a walkway. Step length and gait speed progressively decreased with advancing age; the shorter step length resulted in closer foot placement to the obstacle and an associated increased risk of obstacle contact. Lead (first limb to cross the obstacle) and trail (second) limb trajectories were examined for behavior that mitigated the risk of contact. (1) Consistent trail foot placement before the obstacle across all ages allowed space and time for the trail foot to clear the obstacle. (2) To avoid lead limb contact due to closer foot placement before and after the obstacle, the lead toe was raised more vertically after toe-off, and then the foot was extended beyond the landing position (termed lead overshoot) and retracted backwards to achieve the shortened step length. Lead overshoot progressively increased with advancing age. (3) Head angle was progressively lower with advancing age, an apparent attempt to gather more visual information during approach. Overall, a series of proactive strategies were adopted to mitigate risk of contact. However, the larger, more abrupt movements associated with a more vertical foot trajectory and lead overshoot may compromise whole body balance, indicating a possible trade-off between risk of contact and stability.

  11. Timing of Complementary Food Introduction and Age at Diagnosis of Type 1 Diabetes: the SEARCH Nutrition Ancillary STUDY (SNAS)

    PubMed Central

    Crume, Tessa L.; Crandell, Jamie; Norris, Jill M.; Dabelea, Dana; Fangman, Mary T.; Pettitt, David J.; Dolan, Lawrence; Rodriguez, Beatriz L.; O'Connor, Rebecca; Mayer-Davis, Elizabeth J.

    2015-01-01

    The association between timing of complementary food introduction and age at diagnosis of type 1 diabetes was investigated among 1077 children in the SEARCH for Diabetes in Youth study. Age at diagnosis was 5-month earlier for children introduced to sugar-sweetened beverages (SSB) in the first 12 months of life compared to those who were not (9.0 ± 0.2 vs. 9.5 ± 0.1; p=0.02), independent of HLA-risk status. Analyses stratified by HLA-risk status found that children with a high risk HLA genotype had an earlier age at diagnosis if they were introduced to fruit juice in the first year of life (mean age of diagnosis=9.3 ± 0.1, 9.1 ± 0.1 and 9.6 ± 0.2 for introduction at ≤ 6 months, between 7 and 11 months, and ≤12 months, respectively; p=0.04). Introduction of SSB in the first year of life may accelerate onset of type 1 diabetes independent of HLA-risk status. PMID:25117987

  12. Effects of combined lipoic acid and pyridoxine on albuminuria, advanced glycation end-products, and blood pressure in diabetic nephropathy.

    PubMed

    Noori, Nazanin; Tabibi, Hadi; Hosseinpanah, Farhad; Hedayati, Mehdi; Nafar, Mohsen

    2013-01-01

    This study was designed to investigate the effects of combined administration of lipoic acid and pyridoxine on albuminuria, oxidative stress, blood pressure, serum advanced glycation end-products, nitric oxide (NO), and endothelin-1 in patients with diabetic nephropathy. Thirty-four patients were randomly assigned to either a supplement group or a placebo group. The patients in the supplement group received 800 mg lipoic acid and 80 mg pyridoxine daily for 12 weeks, whereas the placebo group received corresponding placebos. Urinary albumin, serum malondialdehyde (MDA), and systolic blood pressure decreased significantly in the supplement group compared to the placebo group (p < 0.05). Serum NO increased in the supplement group compared to the placebo group (p < 0.05). Serum pentosidine and carboxymethyl lysine decreased significantly in the supplement group at the end of week 12 compared to baseline (p < 0.05). No statistically significant differences were observed between the two groups in mean changes of serum endothelin-1, glucose, and diastolic blood pressure. The present study indicates that combined administration of lipoic acid and pyridoxine improves albuminuria in patients with diabetic nephropathy by reducing oxidative stress, advanced glycation end-products, and systolic blood pressure. The reduction in microalbuminuria may be of benefit in retarding the progression of diabetic nephropathy.

  13. Gait pattern alterations in older adults associated with type 2 diabetes in the absence of peripheral neuropathy--results from the Baltimore Longitudinal Study of Aging.

    PubMed

    Ko, Seung-uk; Stenholm, Sari; Chia, Chee W; Simonsick, Eleanor M; Ferrucci, Luigi

    2011-10-01

    Diabetes may impact gait mechanics before onset of frank neuropathies and other associated threats to mobility. This study aims to characterize gait pattern alterations of type 2 diabetic adults without peripheral neuropathy during walking at maximum speed (fast-walking) as well as at self-selected speed (usual-walking). One-hundred and eighty-six participants aged 60-87 from the Baltimore Longitudinal Study of Aging (BLSA) able to walk unassisted and without peripheral neuropathy were classified as non-diabetic (N=160) or having type 2 diabetes (N=26). Gait parameters from the fast-walking and usual-walking tests were compared between participants with and without type 2 diabetes. Participants with diabetes had a shorter stride length for fast-walking (p=0.033) and a longer percentage of the gait cycle with the knee in 1st flexion for both fast- and usual-walking (p=0.033, and 0.040, respectively) than non-diabetic participants. Participants with diabetes exhibited a smaller hip range of motion in the sagittal plane during usual-walking compared to non-diabetics (p=0.049). During fast-walking, participants with diabetes used lower ankle generative mechanical work expenditure (MWE) and higher knee absorptive MWE compared to non-diabetic persons (p=0.021, and 0.018, respectively). These findings suggest that individuals with type 2 diabetes without overt peripheral neuropathy exhibit altered and less efficient gait patterns than non-diabetic persons. These alterations are more apparent during walking at a maximum speed indicating that maximum gait testing may be useful for identifying early threats to mobility limitations in older adults with type 2 diabetes.

  14. Women Are Diagnosed with Type 2 Diabetes at Higher Body Mass Indices and Older Ages than Men: Korea National Health and Nutrition Examination Survey 2007-2010

    PubMed Central

    2014-01-01

    Background Many epidemiologic studies have shown that women with type 2 diabetes have an increased risk of developing cardiovascular disease compared with men with diabetes. The aim of this study is to elucidate whether disparities of adiposity, age and insulin resistance (IR) at the time of diabetes diagnosis exist between women and men in the adult Korean population. Methods Data from The Korea National Health and Nutrition Examination Survey, performed in Korea from 2007 to 2010, were used. In the survey, anthropometric data and blood samples were obtained during a fasting state. IR and β-cell function were calculated using the homeostasis model assessment (HOMA-IR and HOMA-β, respectvely). Results The mean age of diabetes diagnosis was 58.5 years in women and was 55.1 years in men (P=0.015). The mean body mass index (BMI) of newly diagnosed diabetes subjects was 26.1 kg/m2 in women and 25.0 kg/m2 in men (P=0.001). The BMI was inversely related to age in both genders, and the higher BMI in women than men was consistent throughout all age groups divided by decade. The HOMA-IR in women with diabetes is higher than in men with diabetes (7.25±0.77 vs. 5.20±0.32; P=0.012). Conclusion Korean adult women are diagnosed with type 2 diabetes at higher BMI and older age than men and are more insulin-resistant at the time of diabetes diagnosis. This may help explain why women with diabetes have an increased risk of developing cardiovascular disease after the diagnosis of diabetes, compared to men. PMID:24627831

  15. Lack of association of CFD polymorphisms with advanced age-related macular degeneration

    PubMed Central

    Zeng, Jiexi; Chen, Yuhong; Tong, Zongzhong; Zhou, Xinrong; Zhao, Chao; Wang, Kevin; Hughes, Guy; Kasuga, Daniel; Bedell, Matthew; Lee, Clara; Ferreyra, Henry; Kozak, Igor; Haw, Weldon; Guan, Jean; Shaw, Robert; Stevenson, William; Weishaar, Paul D.; Nelson, Mark H.; Tang, Luosheng

    2010-01-01

    Purpose Age-related macular degeneration (AMD) is the most common cause of irreversible central vision loss worldwide. Research has linked AMD susceptibility with dysregulation of the complement cascade. Typically, complement factor H (CFH), complement factor B (CFB), complement component 2 (C2), and complement component 3 (C3) are associated with AMD. In this paper, we investigated the association between complement factor D (CFD), another factor of the complement system, and advanced AMD in a Caucasian population. Methods Six single nucleotide polymorphisms (SNPs), rs1683564, rs35186399, rs1683563, rs3826945, rs34337649, and rs1651896, across the region covering CFD, were chosen for this study. One hundred and seventy-eight patients with advanced AMD and 161 age-matched normal controls were genotyped. Potential positive signals were further tested in another independent 445 advanced AMD patients and 190 controls. χ2 tests were performed to compare the allele frequencies between case and control groups. Results None of the six SNPs of CFD was found to be significantly associated with advanced AMD in our study. Conclusions Our findings suggest that CFD may not play a major role in the genetic susceptibility to AMD because no association was found between the six SNPs analyzed in the CFD region and advanced AMD. PMID:21139680

  16. Relationship of decrease in fecundity with advancing age to structural changes in mouse endometrium

    PubMed Central

    SHIMIZU, KIYOSHI; YAMADA, JINZO

    2000-01-01

    The aim of this study was to determine whether a relationship exists between decrease in fecundity and structural changes in the antimesometrial endometrium of the mouse. Fecundity was calculated as the number of animals showing a placental sign/number of copulated animals ×100 (%). Structural changes in the endometrium were examined by electron microscopy. A negative correlation between age and fecundity was found. Fecundity was 50% at 7 mo of age. At this age, amorphous material appeared in the region between the basement membrane deep to the luminal epithelium and the subepithelial cells. This material was sometimes attached to the basement membrane. It increased in amount with advancing age, as fecundity decreased. The structure of the uterine luminal epithelial cells did not alter with age. The results indicated that decrease in fecundity with advancing age is correlated with the appearance of amorphous material beneath the basal lamina of the endometrial epithelium. It is suggested that this could impair communication between the luminal epithelium and the endometrial stroma, which plays an important role in implantation. PMID:10697293

  17. Beyond Diabetes: Does Obesity-Induced Oxidative Stress Drive the Aging Process?

    PubMed Central

    Salmon, Adam B.

    2016-01-01

    Despite numerous correlative data, a causative role for oxidative stress in mammalian longevity has remained elusive. However, there is strong evidence that increased oxidative stress is associated with exacerbation of many diseases and pathologies that are also strongly related to advanced age. Obesity, or increased fat accumulation, is one of the most common chronic conditions worldwide and is associated with not only metabolic dysfunction but also increased levels of oxidative stress in vivo. Moreover, obesity is also associated with significantly increased risks of cardiovascular disease, neurological decline and cancer among many other diseases as well as a significantly increased risk of mortality. In this review, we investigate the possible interpretation that the increased incidence of these diseases in obesity may be due to chronic oxidative stress mediating segmental acceleration of the aging process. Understanding how obesity can alter cellular physiology beyond that directly related to metabolic function could open new therapeutic areas of approach to extend the period of healthy aging among people of all body composition. PMID:27438860

  18. Pomegranate (Punicagranatum) juice decreases lipid peroxidation, but has no effect on plasma advanced glycated end-products in adults with type 2 diabetes: a randomized double-blind clinical trial

    PubMed Central

    Sohrab, Golbon; Angoorani, Pooneh; Tohidi, Maryam; Tabibi, Hadi; Kimiagar, Masoud; Nasrollahzadeh, Javad

    2015-01-01

    Introduction Diabetes mellitus characterized by hyperglycemia could increase oxidative stress and formation of advanced glycated end-products (AGEs), which contribute to diabetic complications. The purpose of this study was to assess the effect of pomegranate juice (PJ) containing natural antioxidant on lipid peroxidation and plasma AGEs in patients with type 2 diabetes (T2D). Materials and methods In a randomized, double-blind, placebo-controlled trial, 44 patients (age range 56±6.8 years), T2D were randomly assigned to one of two groups: group A (PJ, n=22) and group B (Placebo, n=22). At the baseline and the end of 12-week intervention, biochemical markers including fasting plasma glucose, insulin, oxidative stress, and AGE markers including carboxy methyl lysine (CML) and pentosidine were assayed. Results At baseline, there were no significant differences in plasma total antioxidant capacity (TAC) levels between the two groups, but malondialdehyde (MDA) decreased levels were significantly different (P<0.001). After 12 weeks of intervention, TAC increased (P<0.05) and MDA decreased (P<0.01) in the PJ group when compared with the placebo group. However, no significant differences were observed in plasma concentration of CML and pentosidine between the two groups. Conclusions The study showed that PJ decreases lipid peroxidation. Therefore, PJ consumption may delay onset of T2D complications related to oxidative stress. PMID:26355954

  19. Histopathological lesions in the pancreas of the BB Wistar rat as a function of age and duration of diabetes.

    PubMed

    Wright, J; Yates, A; Sharma, H; Thibert, P

    1985-01-01

    Pancreatic histopathology was studied in 121 BBWd, 43 BBWnd, and 33 Wistar rats. Insulitis was the most common inflammatory lesion in both BBW and BBWnd rats. The incidence was inversely associated with age and with duration of diabetes in BBWd rats, but there was no age-related pattern in BBWnd rats. Small end-stage islets were typical of BBWd rats but were not seen in BBWnd rats. Several BBWd rats showed hyperplastic islets months after the onset of diabetes, a pattern that is also seen in a small percentage of human JOD patients. Several non-specific exocrine inflammatory lesions occurred in both BBWd and BBWnd rats: acute and/or chronic pancreatitis, eosinophilic infiltrates, granulomatous lesions and acute and/or chronic interstitial inflammation. Only chronic interstitial inflammation was seen in outbred Wistar rats. PMID:3882779

  20. Histopathological lesions in the pancreas of the BB Wistar rat as a function of age and duration of diabetes.

    PubMed

    Wright, J; Yates, A; Sharma, H; Thibert, P

    1985-01-01

    Pancreatic histopathology was studied in 121 BBWd, 43 BBWnd, and 33 Wistar rats. Insulitis was the most common inflammatory lesion in both BBW and BBWnd rats. The incidence was inversely associated with age and with duration of diabetes in BBWd rats, but there was no age-related pattern in BBWnd rats. Small end-stage islets were typical of BBWd rats but were not seen in BBWnd rats. Several BBWd rats showed hyperplastic islets months after the onset of diabetes, a pattern that is also seen in a small percentage of human JOD patients. Several non-specific exocrine inflammatory lesions occurred in both BBWd and BBWnd rats: acute and/or chronic pancreatitis, eosinophilic infiltrates, granulomatous lesions and acute and/or chronic interstitial inflammation. Only chronic interstitial inflammation was seen in outbred Wistar rats.

  1. Younger Dryas Age advance of Franz Josef Glacier in the Southern Alps of New Zealand

    SciTech Connect

    Denton, G.H. ); Hendy, C.H. )

    1994-06-03

    A corrected radiocarbon age of 11,050 [+-] 14 years before present for an advance of the Franz Josef Glacier to the Waiho Loop terminal moraine on the western flank of New Zealand's Southern Alps shows that glacier advance on a South Pacific island was synchronous with initiation of the Younger Dryas in the North Atlantic region. Hence, cooling at the beginning of the Younger Dryas probably reflects global rather than regional forcing. The source for Younger Dryas climatic cooling may thus lie in the atmosphere rather than in a North Atlantic thermohaline switch. 36 refs., 2 figs., 1 tab.

  2. Probit Models to Investigate Prevalence of Total Diagnosed and Undiagnosed Diabetes among Aged 45 Years or Older Adults in China

    PubMed Central

    Yin, Minghui; Augustin, Balekouzou; Shu, Chang; Qin, Tingting; Yin, Ping

    2016-01-01

    The aims of this study are to identify the most important predictors of total diagnosed and undiagnosed diabetes and estimate the mean change in the predicted probability among aged 45+ adults in China. We used baseline data collected from 2011 wave of the China Health and Retirement Longitudinal Study (CHARLS) (n = 9,513). First, we estimated the prevalence of diagnosed, measured, total diagnosed, and undiagnosed diabetes. Second, we used probit models to determine whether individual attributes, socioeconomic characteristics and behavioral health factors, including smoking, alcohol consumption, obesity, central obesity, are associated with total diagnosed and undiagnosed diabetes. We also consider other factors, including contact with medical system, hypertension and urban/rural settings. Third, we estimated average marginal effects of variables in probit models. Among Chinese people aged 45+, the prevalence of diagnosed, measured, total diagnosed and undiagnosed diabetes were 5.8% (95%CI, 5.3%-6.3%), 14.7% (95%CI, 14.0%-15.4%), 17.0% (95%CI, 16.3%-17.7%), 11.3% (95%CI, 10.6%-12.0%), respectively. The probability of total diagnosed diabetes is 3.3% (95% CI, 1.2%-5.3%) and 10.2% (95% CI, 7.0%-13.5%) higher for overweight and obesity than normal BMI, 5.0% (95% CI, 3.0%-7.1%) higher for central obesity than normal waist circumference, 5.4% (95% CI, 3.7%-7.0%) higher for hypertensive than normotensive and 1.8% (95% CI, 0.8%- 2.7%) higher in urban areas than in rural areas, respectively. The probability of undiagnosed diabetes is 2.7% (95% CI, 1.2%-4.2%) and 7.2% (95% CI, 4.7%-9.6%) higher for overweight and obesity than normal BMI, 2.6% (95% CI, 0.9%-4.4%) higher for central obesity than normal waist circumference and 2.6% (95% CI, 1.2%-4.0%) higher for hypertensive than normotensive, respectively, and -1.5% (95% CI, -2.5% to -0.5%) lower for individuals who were in contact with the medical system. Greater focus on prevention of diabetes is necessary for obesity

  3. [Diabetes mellitus and aging as a risk factor for cerebral vascular disease: epidemiology, pathophysiology and prevention].

    PubMed

    Cantú-Brito, Carlos; Mimenza-Alvarado, Alberto; Sánchez-Hernández, Juan José

    2010-01-01

    Older patients with diabetes have a high risk of vascular complications. They have an increase of approximately 3 times for developing stroke compared with subjects without diabetes. In addition, up to 75-80% of deaths in diabetic patients are associated with major cardiovascular events including stroke. The risk of stroke is high within 5 years of diagnosis for type 2 diabetes is 9% (mortality 21%), that is more than doubles the rate for the general population. From observational registries in a collaborative stroke study in Mexico, we analyzed clinical data, risk factors, and outcome of 1182 diabetic patients with cerebral ischemia, with focus in elderly subjects. There was a high frequency of hyperglycemia during the acute phase of stroke: the median value was 140 mg/dL and 40% had values higher than 180 mg/dL. Clinical outcome was usually unfavorable in elderly stroke patients with diabetes: case fatality rate was 30% at 30 days and survivors had moderate to severe disability, usually as consequence of the propensity to develop more systemic medical complications during hospital stay. Primary stroke prevention studies in patients with diabetes reveal that tight control of glucose is not associated with reduction in stroke risk. Therefore, proper control of other vascular risk factors is mandatory in patients with diabetes, in particular of arterial hypertension.

  4. [Diabetes mellitus and aging as a risk factor for cerebral vascular disease: epidemiology, pathophysiology and prevention].

    PubMed

    Cantú-Brito, Carlos; Mimenza-Alvarado, Alberto; Sánchez-Hernández, Juan José

    2010-01-01

    Older patients with diabetes have a high risk of vascular complications. They have an increase of approximately 3 times for developing stroke compared with subjects without diabetes. In addition, up to 75-80% of deaths in diabetic patients are associated with major cardiovascular events including stroke. The risk of stroke is high within 5 years of diagnosis for type 2 diabetes is 9% (mortality 21%), that is more than doubles the rate for the general population. From observational registries in a collaborative stroke study in Mexico, we analyzed clinical data, risk factors, and outcome of 1182 diabetic patients with cerebral ischemia, with focus in elderly subjects. There was a high frequency of hyperglycemia during the acute phase of stroke: the median value was 140 mg/dL and 40% had values higher than 180 mg/dL. Clinical outcome was usually unfavorable in elderly stroke patients with diabetes: case fatality rate was 30% at 30 days and survivors had moderate to severe disability, usually as consequence of the propensity to develop more systemic medical complications during hospital stay. Primary stroke prevention studies in patients with diabetes reveal that tight control of glucose is not associated with reduction in stroke risk. Therefore, proper control of other vascular risk factors is mandatory in patients with diabetes, in particular of arterial hypertension. PMID:21222313

  5. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes

    PubMed Central

    Bacos, Karl; Gillberg, Linn; Volkov, Petr; Olsson, Anders H; Hansen, Torben; Pedersen, Oluf; Gjesing, Anette Prior; Eiberg, Hans; Tuomi, Tiinamaija; Almgren, Peter; Groop, Leif; Eliasson, Lena; Vaag, Allan; Dayeh, Tasnim; Ling, Charlotte

    2016-01-01

    Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26–74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D. PMID:27029739

  6. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes.

    PubMed

    Bacos, Karl; Gillberg, Linn; Volkov, Petr; Olsson, Anders H; Hansen, Torben; Pedersen, Oluf; Gjesing, Anette Prior; Eiberg, Hans; Tuomi, Tiinamaija; Almgren, Peter; Groop, Leif; Eliasson, Lena; Vaag, Allan; Dayeh, Tasnim; Ling, Charlotte

    2016-03-31

    Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D.

  7. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes.

    PubMed

    Bacos, Karl; Gillberg, Linn; Volkov, Petr; Olsson, Anders H; Hansen, Torben; Pedersen, Oluf; Gjesing, Anette Prior; Eiberg, Hans; Tuomi, Tiinamaija; Almgren, Peter; Groop, Leif; Eliasson, Lena; Vaag, Allan; Dayeh, Tasnim; Ling, Charlotte

    2016-01-01

    Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D. PMID:27029739

  8. Obesity and diabetes genes are associated with being born small for gestational age: Results from the Auckland Birthweight Collaborative study

    PubMed Central

    2010-01-01

    Background Individuals born small for gestational age (SGA) are at increased risk of rapid postnatal weight gain, later obesity and diseases in adulthood such as type 2 diabetes, hypertension and cardiovascular diseases. Environmental risk factors for SGA are well established and include smoking, low pregnancy weight, maternal short stature, maternal diet, ethnic origin of mother and hypertension. However, in a large proportion of SGA, no underlying cause is evident, and these individuals may have a larger genetic contribution. Methods In this study we tested the association between SGA and polymorphisms in genes that have previously been associated with obesity and/or diabetes. We undertook analysis of 54 single nucleotide polymorphisms (SNPs) in 546 samples from the Auckland Birthweight Collaborative (ABC) study. 227 children were born small for gestational age (SGA) and 319 were appropriate for gestational age (AGA). Results and Conclusion The results demonstrated that genetic variation in KCNJ11, BDNF, PFKP, PTER and SEC16B were associated with SGA and support the concept that genetic factors associated with obesity and/or type 2 diabetes are more prevalent in those born SGA compared to those born AGA. We have previously determined that environmental factors are associated with differences in birthweight in the ABC study and now we have demonstrated a significant genetic contribution, suggesting that the interaction between genetics and the environment are important. PMID:20712903

  9. Exendin-4 Reduces Ischemic Brain Injury in Normal and Aged Type 2 Diabetic Mice and Promotes Microglial M2 Polarization

    PubMed Central

    Larsson, Martin; Mallard, Carina; Nathanson, David; Nyström, Thomas; Sjöholm, Åke; Johansson, Maria E.; Patrone, Cesare

    2014-01-01

    Exendin-4 is a glucagon-like receptor 1 agonist clinically used against type 2 diabetes that has also shown neuroprotective effects in experimental stroke models. However, while the neuroprotective efficacy of Exendin-4 has been thoroughly investigated if the pharmacological treatment starts before stroke, the therapeutic potential of the Exendin-4 if the treatment starts acutely after stroke has not been clearly determined. Further, a comparison of the neuroprotective efficacy in normal and aged diabetic mice has not been performed. Finally, the cellular mechanisms behind the efficacy of Exendin-4 have been only partially studied. The main objective of this study was to determine the neuroprotective efficacy of Exendin-4 in normal and aged type 2 diabetic mice if the treatment started after stroke in a clinically relevant setting. Furthermore we characterized the Exendin-4 effects on stroke-induced neuroinflammation. Two-month-old healthy and 14-month-old type 2 diabetic/obese mice were subjected to middle cerebral artery occlusion. 5 or 50 µg/kg Exendin-4 was administered intraperitoneally at 1.5, 3 or 4.5 hours thereafter. The treatment was continued (0.2 µg/kg/day) for 1 week. The neuroprotective efficacy was assessed by stroke volume measurement and stereological counting of NeuN-positive neurons. Neuroinflammation was determined by gene expression analysis of M1/M2 microglia subtypes and pro-inflammatory cytokines. We show neuroprotective efficacy of 50 µg/kg Exendin-4 at 1.5 and 3 hours after stroke in both young healthy and aged diabetic/obese mice. The 5 µg/kg dose was neuroprotective at 1.5 hour only. Proinflammatory markers and M1 phenotype were not impacted by Exendin-4 treatment while M2 markers were significantly up regulated. Our results support the use of Exendin-4 to reduce stroke-damage in the prehospital/early hospitalization setting irrespectively of age/diabetes. The results indicate the polarization of microglia/macrophages towards the M2

  10. Microsurgical varicocelectomy for infertile couples with advanced female age: natural history in the era of ART.

    PubMed

    O'Brien, Jeanne H; Bowles, Ben; Kamal, Khaled M; Jarvi, Keith; Zini, Armand

    2004-01-01

    Varicocele represents the most common cause of male infertility, and most reports indicate that varicocelectomy has a beneficial effect on male fertility and pregnancy outcome. Assisted reproductive technologies (ARTs) are an alternative to varicocelectomy for the management of couples with a varicocele. The age of the female partner is important in the decision-making process; however, the true influence of female age on pregnancy outcome following varicocelectomy or ART in these couples is unknown. We evaluated the outcomes of 2 cohorts of infertile men with a varicocele and a female partner 35 years of age or older; one group selected varicocelectomy and the other a nonsurgical approach. We reviewed a group of consecutive infertile men who underwent microsurgical varicocelectomy and whose partners are 35 years of age or older (n = 110). We also reviewed a consecutive group of men with varicoceles who elected not to have surgery and whose partners are 35 years of age or older (n = 94). The outcome measures included changes in semen parameters, pregnancy rates (assisted and unassisted), and use of ART. The surgical and nonsurgical groups had comparable semen parameters and female ages. Mean sperm concentration and motility increased significantly after varicocelectomy (P < .05). At a mean of 30 months follow-up, 35% of couples in the surgical group achieved a spontaneous pregnancy and an additional 6% achieved a pregnancy via ART (20% of this group attempted ART). In the nonsurgical group, 25% achieved a spontaneous pregnancy and an additional 16% achieved a pregnancy with ART (40% of this group attempted ART). This study on the natural history of infertile men with varicocele and advanced female age suggests that the surgical and nonsurgical approaches offer comparable pregnancy outcome (combined assisted and unassisted pregnancy rates are about 40%). Overall, these data suggest that varicocelectomy is an acceptable option for couples with advanced female age

  11. Bone Formation is Affected by Matrix Advanced Glycation End Products (AGEs) In Vivo.

    PubMed

    Yang, Xiao; Mostafa, Ahmed Jenan; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu

    2016-10-01

    Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Although previous evidence shows that the accumulation of AGEs in bone matrix may impose significant effects on bone cells, the effect of matrix AGEs on bone formation in vivo is still poorly understood. To address this issue, this study used a unique rat model with autograft implant to investigate the in vivo response of bone formation to matrix AGEs. Fluorochrome biomarkers were sequentially injected into rats to label the dynamic bone formation in the presence of elevated levels of matrix AGEs. After sacrificing animals, dynamic histomorphometry was performed to determine mineral apposition rate (MAR), mineralized surface per bone surface (MS/BS), and bone formation rate (BFR). Finally, nanoindentation tests were performed to assess mechanical properties of newly formed bone tissues. The results showed that MAR, MS/BS, and BFR were significantly reduced in the vicinity of implant cores with high concentration of matrix AGEs, suggesting that bone formation activities by osteoblasts were suppressed in the presence of elevated matrix AGEs. In addition, MAR and BFR were found to be dependent on the surrounding environment of implant cores (i.e., cortical or trabecular tissues). Moreover, MS/BS and BFR were also dependent on how far the implant cores were away from the growth plate. These observations suggest that the effect of matrix AGEs on bone formation is dependent on the biological milieu around the implants. Finally, nanoindentation test results indicated that the indentation modulus and hardness of newly formed bone tissues were not affected by the presence of elevated matrix AGEs. In summary, high concentration of matrix AGEs may slow down the bone formation process in vivo, while imposing little effects on bone mineralization.

  12. Sleepwalking Into Infertility: The Need for a Public Health Approach Toward Advanced Maternal Age.

    PubMed

    Lemoine, Marie-Eve; Ravitsky, Vardit

    2015-01-01

    In Western countries today, a growing number of women delay motherhood until their late 30s and even 40s, as they invest time in pursuing education and career goals before starting a family. This social trend results from greater gender equality and expanded opportunities for women and is influenced by the availability of contraception and assisted reproductive technologies (ART). However, advanced maternal age is associated with increased health risks, including infertility. While individual medical solutions such as ART and elective egg freezing can promote reproductive autonomy, they entail significant risks and limitations. We thus argue that women should be better informed regarding the risks of advanced maternal age and ART, and that these individual solutions need to be supplemented by a public health approach, including policy measures that provide women with the opportunity to start a family earlier in life without sacrificing personal career goals. PMID:26575814

  13. Sleepwalking Into Infertility: The Need for a Public Health Approach Toward Advanced Maternal Age.

    PubMed

    Lemoine, Marie-Eve; Ravitsky, Vardit

    2015-01-01

    In Western countries today, a growing number of women delay motherhood until their late 30s and even 40s, as they invest time in pursuing education and career goals before starting a family. This social trend results from greater gender equality and expanded opportunities for women and is influenced by the availability of contraception and assisted reproductive technologies (ART). However, advanced maternal age is associated with increased health risks, including infertility. While individual medical solutions such as ART and elective egg freezing can promote reproductive autonomy, they entail significant risks and limitations. We thus argue that women should be better informed regarding the risks of advanced maternal age and ART, and that these individual solutions need to be supplemented by a public health approach, including policy measures that provide women with the opportunity to start a family earlier in life without sacrificing personal career goals.

  14. Advancing maternal age and trisomy screening: the practice challenges of facilitating choice and gaining consent.

    PubMed

    Birt, Maria

    2015-12-01

    Antenatal screening for chromosomal anomalies such as Trisomy 13, 18 and 21 (Patau's, Edward's and Down's syndrome respectively) is offered to all pregnant women in the first two trimesters.This article explores the varying considerations of consent for this type of screening, particularly in relation to women of advancing age who are at increased risk of carrying a pregnancy affected by a trisomy. The practical challenges or barriers of gaining valid, meaningful informed consent are discussed. PMID:26753259

  15. Proteome-wide alterations on adipose tissue from obese patients as age-, diabetes- and gender-specific hallmarks

    PubMed Central

    Gómez-Serrano, María; Camafeita, Emilio; García-Santos, Eva; López, Juan A.; Rubio, Miguel A.; Sánchez-Pernaute, Andrés; Torres, Antonio; Vázquez, Jesús; Peral, Belén

    2016-01-01

    Obesity is a main global health issue and an outstanding cause of morbidity and mortality predisposing to type 2 diabetes (T2DM) and cardiovascular diseases. Huge research efforts focused on gene expression, cellular signalling and metabolism in obesity have improved our understanding of these disorders; nevertheless, to bridge the gap between the regulation of gene expression and changes in signalling/metabolism, protein levels must be assessed. We have extensively analysed visceral adipose tissue from age-, T2DM- and gender-matched obese patients using high-throughput proteomics and systems biology methods to identify new biomarkers for the onset of T2DM in obesity, as well as to gain insight into the influence of aging and gender in these disorders. About 250 proteins showed significant abundance differences in the age, T2DM and gender comparisons. In diabetic patients, remarkable gender-specific hallmarks were discovered regarding redox status, immune response and adipose tissue accumulation. Both aging and T2DM processes were associated with mitochondrial remodelling, albeit through well-differentiated proteome changes. Systems biology analysis highlighted mitochondrial proteins that could play a key role in the age-dependent pathophysiology of T2DM. Our findings could serve as a framework for future research in Translational Medicine directed at improving the quality of life of obese patients. PMID:27160966

  16. Age dependence of glucose tolerance in adult KK-Ay mice, a model of non-insulin dependent diabetes mellitus.

    PubMed

    Chakraborty, Goutam; Thumpayil, Sherin; Lafontant, David-Erick; Woubneh, Wolde; Toney, Jeffrey H

    2009-11-01

    Yellow KK mice carrying the 'yellow obese' gene Ay are a well established polygenic model for human non-insulin dependent diabetes mellitus. These animals develop marked adiposity and decreased glucose tolerance relative to their control littermates, KK mice. The authors monitored glucose tolerance in KK-Ay mice over time and observed a significant (Page-dependent improvement (13.3% by 175 d of age and 36.4% by 212 d of age, relative to 85 d of age). During the same time period, body weight and food and water consumption were relatively constant. The authors also measured plasma levels of endocrine hormones that are important in diabetes. Levels of insulin were approximately 8 times higher and levels of amylin 3 times higher in 220-d-old KK-Ay mice than in 180-d-old mice, whereas levels of glucagon-like peptide 1, glucagon and leptin remained relatively constant. These findings suggest that KK-Ay mice undergo an age-dependent improvement of glucose tolerance when maintained on a normal diet for 25 weeks or longer, due in part to increases in plasma levels of insulin and amylin.

  17. Proteome-wide alterations on adipose tissue from obese patients as age-, diabetes- and gender-specific hallmarks.

    PubMed

    Gómez-Serrano, María; Camafeita, Emilio; García-Santos, Eva; López, Juan A; Rubio, Miguel A; Sánchez-Pernaute, Andrés; Torres, Antonio; Vázquez, Jesús; Peral, Belén

    2016-01-01

    Obesity is a main global health issue and an outstanding cause of morbidity and mortality predisposing to type 2 diabetes (T2DM) and cardiovascular diseases. Huge research efforts focused on gene expression, cellular signalling and metabolism in obesity have improved our understanding of these disorders; nevertheless, to bridge the gap between the regulation of gene expression and changes in signalling/metabolism, protein levels must be assessed. We have extensively analysed visceral adipose tissue from age-, T2DM- and gender-matched obese patients using high-throughput proteomics and systems biology methods to identify new biomarkers for the onset of T2DM in obesity, as well as to gain insight into the influence of aging and gender in these disorders. About 250 proteins showed significant abundance differences in the age, T2DM and gender comparisons. In diabetic patients, remarkable gender-specific hallmarks were discovered regarding redox status, immune response and adipose tissue accumulation. Both aging and T2DM processes were associated with mitochondrial remodelling, albeit through well-differentiated proteome changes. Systems biology analysis highlighted mitochondrial proteins that could play a key role in the age-dependent pathophysiology of T2DM. Our findings could serve as a framework for future research in Translational Medicine directed at improving the quality of life of obese patients. PMID:27160966

  18. Screening of Undiagnosed Hypothyroidism in Elderly Persons with Diabetes according to Age-Specific Reference Intervals for Serum Thyroid Stimulating Hormone and the Impact of Antidiabetes Drugs.

    PubMed

    Fontes, Rosita; Teixeira, Patricia de Fatima Dos Santos; Vaisman, Mario

    2016-01-01

    Background. Studies have suggested that hypothyroidism is more frequent in the elderly with diabetes mellitus. However, an adaptation of TSH levels to age should be considered in this assessment. Some antidiabetes drugs reportedly interfere with TSH levels. The objectives of this study were to evaluate the prevalence of undiagnosed hypothyroidism in patients with diabetes and the influence of antidiabetes drugs. Material and Methods. 1160 subjects, 60 years and older (751 with diabetes), were studied; results were compared according to diabetes treatment and with persons without diabetes. TSH, FT4, antithyroperoxidase, fasting glucose, and HbA1c were measured. Results and Discussion. 6.4% of patients with diabetes had hypothyroidism, a higher prevalence compared with persons without diabetes (5.1%), but lower than observed in many studies. The use of age-specific TSH reference interval (RI) could explain this difference. Patients taking metformin (MTF) had TSH (showed in medians) slightly lower (2.8 mU/L) than those not on MTF (3.3 mU/L), p < 0.05. MTF doses influenced TSH levels. Conclusions. The use of specific TSH RI could avoid the misdiagnosis of hypothyroidism in elderly with diabetes. Patients in use of MTF as single drug had lower TSH than those using other medications and persons without diabetes. PMID:27403442

  19. Screening of Undiagnosed Hypothyroidism in Elderly Persons with Diabetes according to Age-Specific Reference Intervals for Serum Thyroid Stimulating Hormone and the Impact of Antidiabetes Drugs

    PubMed Central

    Teixeira, Patricia de Fatima dos Santos; Vaisman, Mario

    2016-01-01

    Background. Studies have suggested that hypothyroidism is more frequent in the elderly with diabetes mellitus. However, an adaptation of TSH levels to age should be considered in this assessment. Some antidiabetes drugs reportedly interfere with TSH levels. The objectives of this study were to evaluate the prevalence of undiagnosed hypothyroidism in patients with diabetes and the influence of antidiabetes drugs. Material and Methods. 1160 subjects, 60 years and older (751 with diabetes), were studied; results were compared according to diabetes treatment and with persons without diabetes. TSH, FT4, antithyroperoxidase, fasting glucose, and HbA1c were measured. Results and Discussion. 6.4% of patients with diabetes had hypothyroidism, a higher prevalence compared with persons without diabetes (5.1%), but lower than observed in many studies. The use of age-specific TSH reference interval (RI) could explain this difference. Patients taking metformin (MTF) had TSH (showed in medians) slightly lower (2.8 mU/L) than those not on MTF (3.3 mU/L), p < 0.05. MTF doses influenced TSH levels. Conclusions. The use of specific TSH RI could avoid the misdiagnosis of hypothyroidism in elderly with diabetes. Patients in use of MTF as single drug had lower TSH than those using other medications and persons without diabetes. PMID:27403442

  20. Autogenous brachio-cephalic arterio-venousautogenous brachio-cephalic arterio-venous fistulae: effect of age, diabetes,fistulae: effect of age, diabetes, atherosclerosis, and anticoagulation on theatherosclerosis, and anticoagulation on the long-term outcomelong-term outcome.

    PubMed

    Papalois, Vassilios E; Ndzengue, Albert; Choi, Peter; Hakim, Nadey S

    2008-01-01

    Age, diabetes, and generalized atherosclerosis are thought to be limiting factors forAge, diabetes, and generalized atherosclerosis are thought to be limiting factors for creating an autogenous arterio-venous fistula (AVF) unlike the use of anticoagulants. Wecreating an autogenous arterio-venous fistula (AVF) unlike the use of anticoagulants. We retrospectively assessed the effect of these factors on the outcome of 75 autogenousretrospectively assessed the effect of these factors on the outcome of 75 autogenous brachio-cephalic AVFs created between January 1, 2002 and August 31, 2005. Differentbrachio-cephalic AVFs created between January 1, 2002 and August 31, 2005. Different groups of patients were compared and the longevity of the AVFs was calculated. Fifty-twogroups of patients were compared and the longevity of the AVFs was calculated. Fifty-two percent of the patients were >65 years old, 41.3% werepercent of the patients were >65 years old, 41.3% were diabetic, 48% were arteriopaths,diabetic, 48% were arteriopaths, and 41.3% were not using anticoagulants. The maximum follow-up was 35 months (mean,and 41.3% were not using anticoagulants. The maximum follow-up was 35 months (mean, 11.2 +/- 10.3 months; median, 7 months). The success rate of the operation was 93.3% (mean 11.2 +/- 10.3 months; median, 7 months). The success rate of the operation was 93.3% (70 patent AVFs); 79.3% of the AVFs were functioning at 35 months. Age >65 years old,patent AVFs); 79.3% of the AVFs were functioning at 35 months. Age >65 years old, diabetes, generalized atherosclerosis, and the lack of use of anticoagulants were notdiabetes, generalized atherosclerosis, and the lack of use of anticoagulants were not associated with an increased rate of technical failures or a decreased long-term patencyassociated with an increased rate of technical failures or a decreased long-term patency rate of the AVFs.rate of the AVFs. PMID:19731852

  1. Changes in splicing factor expression are associated with advancing age in man.

    PubMed

    Holly, Alice C; Melzer, David; Pilling, Luke C; Fellows, Alexander C; Tanaka, Toshiko; Ferrucci, Luigi; Harries, Lorna W

    2013-09-01

    Human ageing is associated with decreased cellular plasticity and adaptability. Changes in alternative splicing with advancing age have been reported in man, which may arise from age-related alterations in splicing factor expression. We determined whether the mRNA expression of key splicing factors differed with age, by microarray analysis in blood from two human populations and by qRT-PCR in senescent primary fibroblasts and endothelial cells. Potential regulators of splicing factor expression were investigated by siRNA analysis. Approximately one third of splicing factors demonstrated age-related transcript expression changes in two human populations. Ataxia Telangiectasia Mutated (ATM) transcript expression correlated with splicing factor expression in human microarray data. Senescent primary fibroblasts and endothelial cells also demonstrated alterations in splicing factor expression, and changes in alternative splicing. Targeted knockdown of the ATM gene in primary fibroblasts resulted in up-regulation of some age-responsive splicing factor transcripts. We conclude that isoform ratios and splicing factor expression alters with age in vivo and in vitro, and that ATM may have an inhibitory role on the expression of some splicing factors. These findings suggest for the first time that ATM, a core element in the DNA damage response, is a key regulator of the splicing machinery in man.

  2. The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: an observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial

    PubMed Central

    Blomster, Juuso I; Woodward, Mark; Zoungas, Sophia; Hillis, Graham S; Harrap, Stephen; Neal, Bruce; Poulter, Neil; Mancia, Giuseppe; Chalmers, John; Huxley, Rachel

    2016-01-01

    Objectives In general populations, the adverse effects of smoking on coronary risk have been demonstrated to be greater in women than in men; whether this is true for individuals with diabetes is unclear. Design Cohort study. Setting 20 countries worldwide participating in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial. Participants 11 140 patients with type 2 diabetes aged ≥55 years and in cardiovascular risk at the time of randomisation. Primary and secondary outcome measures Major cardiovascular events (death from cardiovascular disease, non-fatal stroke or non-fatal myocardial infarction (MI)), all cardiovascular events (major cardiovascular event or peripheral arterial disease or transient ischaemic attack), and all-cause mortality. Secondary outcome measures were major coronary events (fatal and non-fatal MI), major cerebrovascular events (fatal and non-fatal stroke), nephropathy (new or worsening renal disease), and all cancer. Results At baseline, 6466 (56% women) participants were never-smokers, 1550 (28% women) were daily smokers and 3124 (21% women) were former smokers. Median follow-up time was 5 years. In Cox regression models after multiple adjustments, compared with never smoking, daily smoking was associated with increased risk of all primary and secondary outcomes with the exception of major cerebrovascular disease. Only for major coronary events was there any evidence of a stronger effect in women than in men (ratio of the adjusted HRs women:men; 1.64 (0.83 to 3.26) p=0.08). For all other outcomes considered, the hazards of smoking were similar in men and women. Quitting smoking was associated with a 30% reduction in all-cause mortality (p=0.001) in both sexes. Conclusions In individuals with diabetes, the effects of smoking on all major forms of cardiovascular disease are equally as hazardous in women and men with the possible exception of major coronary events

  3. Barriers to eye care among people aged 40 years and older with diagnosed diabetes, 2006-2010.

    PubMed

    Chou, Chiu-Fang; Sherrod, Cheryl E; Zhang, Xinzhi; Barker, Lawrence E; Bullard, Kai McKeever; Crews, John E; Saaddine, Jinan B

    2014-01-01

    OBJECTIVE We examine barriers to receiving recommended eye care among people aged ≥40 years with diagnosed diabetes. RESEARCH DESIGN AND METHODS We analyzed 2006-2010 Behavioral Risk Factor Surveillance System data from 22 states (n = 27,699). Respondents who had not sought eye care in the preceding 12 months were asked the main reason why. We categorized the reasons as cost/lack of insurance, no need, no eye doctor/travel/appointment, and other (meaning everything else). We used multinomial logistic regression to control for race/ethnicity, education, income, and other selected covariates. RESULTS Among adults with diagnosed diabetes, nonadherence to the recommended annual eye examinations was 23.5%. The most commonly reported reasons for not receiving eye care in the preceding 12 months were "no need" and "cost or lack of insurance" (39.7 and 32.3%, respectively). Other reasons were "no eye doctor," "no transportation" or "could not get appointment" (6.4%), and "other" (21.5%). After controlling for covariates, adults aged 40-64 years were more likely than those aged ≥65 years (relative risk ratio [RRR] = 2.79; 95% CI 2.01-3.89) and women were more likely than men (RRR = 2.33; 95% CI 1.75-3.14) to report "cost or lack of insurance" as their main reason. However, people aged 40-64 years were less likely than those aged ≥65 years to report "no need" (RRR = 0.51; 95% CI 0.39-0.67) as their main reason. CONCLUSIONS Addressing concerns about "cost or lack of insurance" for adults under 65 years and "no perceived need" among those 65 years and older could help improve eye care service utilization among people with diabetes. PMID:24009300

  4. Earlier age at menarche is associated with higher diabetes risk and cardiometabolic disease risk factors in Brazilian adults: Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

    PubMed Central

    2014-01-01

    Objectives Early menarche has been linked to higher risk of type 2 diabetes in Western and Asian societies, yet whether age at menarche is associated with diabetes in Latin America, where puberty and diabetes may have different life courses, is unknown. We tested the hypothesis that earlier menarche is associated with higher diabetes risk in Brazilian adults. Methods We used data from 8,075 women aged 35-74 years in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who had complete information on age at menarche, diabetes status, and covariates. Diabetes was defined based on self-reported physician diagnosis, medication use, and laboratory variables (fasting glucose, 2-hour glucose, and glycated hemoglobin). Poisson regression was used to generate risk ratios (RR) and 95% confidence intervals (CI). Results Menarche onset < 11 years [vs. 13-14 years (referent)] was associated with higher risk of diabetes (RR = 1.34; 95% CI: 1.14-1.57) after adjusting for sociodemographic factors, maternal education, maternal and paternal diabetes, and birth weight. This persisted after further control for BMI at age 20 years and relative leg length. Additionally, among those not taking diabetes medications, earlier menarche [<11 years vs. 13-14 years (referent)] was associated with higher % glycated hemoglobin (p < 0.001), alanine aminotransferase (p < 0.001), triglycerides (p < 0.001), C-reactive protein (p = 0.003), waist circumference (p < 0.001), and BMI measured at baseline exam (p < 0.001). Conclusion These findings support the hypothesis that earlier menarche is associated with greater risk for adult diabetes and cardiometabolic disease in the Brazilian context. PMID:24438044

  5. Reduction of diabetic foot ulcer healing times through use of advanced treatment modalities.

    PubMed

    Mulder, Gerit; Tenenhaus, Mayer; D'Souza, Gehaan F

    2014-12-01

    Diabetic wounds are a major health care problem associated with delayed healing and high amputation rates. This review systematically evaluated newer wound care therapies for the treatment of diabetic wounds. More recent means of approaching diabetic foot ulcers include various dressings, off-loading shoes, and bioengineered skin constructs and growth factors. Electrical stimulation, phototherapy, electromagnetic fields, and shockwave therapy have been further proposed as potential treatments. A brief overview of these treatments is presented using peer-reviewed evidenced-based literature. A review of the literature demonstrated that treatment of diabetic wounds has focused on either prevention of the wounds in the form of off-loading shoes or adequate protective dressings or on direct treatment of wounds with bioengineered skin constructs, growth factors, or medical devices that accelerate wound healing. The authors' conclusion, following extensive literature review, is that although excellent national and international guidelines exist regarding suggested approaches to the treatment of the diabetic foot ulcer, there is no definitive or universal consensus on the choice of specific treatment modalities. The importance of optimizing comorbidities and the disease state, hemodynamics, local and peripheral skin and wound care, and metabolic challenges while reducing biological and bacterial burden and minimizing trauma remain the primary approach, followed by choice of the most appropriate treatment material or product.

  6. Translating Advances from the Basic Biology of Aging into Clinical Application

    PubMed Central

    Kirkland, James L.

    2013-01-01

    Recently, lifespan and healthspan have been extended in experimental animals using interventions that are potentially translatable into humans. A great deal of thought and work are needed beyond the usual steps in drug development to advance these findings into clinical application. Realistic pre-clinical and clinical trials paradigms need to be devised. Focusing on subjects with symptoms of age-related diseases or frailty or who are at imminent risk of developing these problems, measuring effects on short-term, clinically relevant outcomes, as opposed to long-term outcomes such as healthspan or lifespan, and developing biomarkers and outcome measures acceptable to regulatory agencies will be important. Research funding is a major roadblock, as is lack of investigators with combined expertise in the basic biology of aging, clinical geriatrics, and conducting investigational new drug clinical trials. Options are reviewed for developing a path from the bench to the bedside for interventions that target fundamental aging processes. PMID:23237984

  7. Risk of Malignant Neoplasms of Kidney and Bladder in a Cohort Study of the Diabetic Population in Taiwan With Age, Sex, and Geographic Area Stratifications.

    PubMed

    Chen, Hua-Fen; Chen, Shwe-Winn; Chang, Ya-Hui; Li, Chung-Yi

    2015-09-01

    Diabetes has been reported to increase the risk of malignant neoplasms of kidney and bladder, but the studies' results are still inconclusive. Age, sex, and geographical area-specific incidence and relative risks of above neoplasms are also scarce in the literature. We prospectively investigated the age, sex, geographical area-specific incidence and relative risks of kidney and bladder neoplasms in diabetic population of Taiwan. Diabetic patients (n = 615,532) and age- and sex-matched controls (n = 614,871) were linked to inpatient claims (2000-2008) to identify the admissions for malignant neoplasm of kidney (International Classification of Diagnosis, 9th version, Clinical Modification: 189) and bladder (International Classification of Diagnosis, 9th version, Clinical Modification: 188). The person-year approach with Poisson assumption was used to evaluate the incidence density. We also estimated the age, sex, and geographical area-specific relative risks of above malignancy in relation to diabetes with Cox proportional hazard regression model. The overall incidence density of malignant neoplasm of kidney for diabetic men and women were 3.87 and 4.28 per 10,000 patient-years, respectively; the corresponding figures for malignant neoplasm of bladder were 5.73 and 3.25 per 10,000 patient-years. Compared with the controls, diabetic men were at significantly increased hazards of kidney (covariate adjusted hazard ratio [aHR]: 1.31, 95% confidence interval [CI] 1.18-1.46) and bladder aHR: 1.13, 95% CI 1.04-1.23). Diabetic women, on the contrary, only experienced significantly elevated hazard of kidney neoplasm (aHR: 1.14, 95% CI 1.04-1.26). Diabetic men aged >65 years showed the most significantly increased hazard of developing neoplasm of kidney (aHR: 1.40) and bladder (aHR: 1.13). The most significantly increased hazard of kidney neoplasm was noted for women diabetic patients aged >65 years. There was also a significant interactive effect of geographic area

  8. Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring.

    PubMed

    Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

    2014-08-01

    While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span.

  9. Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring.

    PubMed

    Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

    2014-08-01

    While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. PMID:24661622

  10. Interactive effects of vascular risk burden and advanced age on cerebral blood flow

    PubMed Central

    Bangen, Katherine J.; Nation, Daniel A.; Clark, Lindsay R.; Harmell, Alexandrea L.; Wierenga, Christina E.; Dev, Sheena I.; Delano-Wood, Lisa; Zlatar, Zvinka Z.; Salmon, David P.; Liu, Thomas T.; Bondi, Mark W.

    2014-01-01

    Vascular risk factors and cerebral blood flow (CBF) reduction have been linked to increased risk of cognitive impairment and Alzheimer's disease (AD); however the possible moderating effects of age and vascular risk burden on CBF in late life remain understudied. We examined the relationships among elevated vascular risk burden, age, CBF, and cognition. Seventy-one non-demented older adults completed an arterial spin labeling MR scan, neuropsychological assessment, and medical history interview. Relationships among vascular risk burden, age, and CBF were examined in a priori regions of interest (ROIs) previously implicated in aging and AD. Interaction effects indicated that, among older adults with elevated vascular risk burden (i.e., multiple vascular risk factors), advancing age was significantly associated with reduced cortical CBF whereas there was no such relationship for those with low vascular risk burden (i.e., no or one vascular risk factor). This pattern was observed in cortical ROIs including medial temporal (hippocampus, parahippocampal gyrus, uncus), inferior parietal (supramarginal gyrus, inferior parietal lobule, angular gyrus), and frontal (anterior cingulate, middle frontal gyrus, medial frontal gyrus) cortices. Furthermore, among those with elevated vascular risk, reduced CBF was associated with poorer cognitive performance. Such findings suggest that older adults with elevated vascular risk burden may be particularly vulnerable to cognitive change as a function of CBF reductions. Findings support the use of CBF as a potential biomarker in preclinical AD and suggest that vascular risk burden and regionally-specific CBF changes may contribute to differential age-related cognitive declines. PMID:25071567

  11. The Age-Specific Quantitative Effects of Metabolic Risk Factors on Cardiovascular Diseases and Diabetes: A Pooled Analysis

    PubMed Central

    Farzadfar, Farshad; Stevens, Gretchen A.; Woodward, Mark; Wormser, David; Kaptoge, Stephen; Whitlock, Gary; Qiao, Qing; Lewington, Sarah; Di Angelantonio, Emanuele; vander Hoorn, Stephen; Lawes, Carlene M. M.; Ali, Mohammed K.; Mozaffarian, Dariush; Ezzati, Majid

    2013-01-01

    Background The effects of systolic blood pressure (SBP), serum total cholesterol (TC), fasting plasma glucose (FPG), and body mass index (BMI) on the risk of cardiovascular diseases (CVD) have been established in epidemiological studies, but consistent estimates of effect sizes by age and sex are not available. Methods We reviewed large cohort pooling projects, evaluating effects of baseline or usual exposure to metabolic risks on ischemic heart disease (IHD), hypertensive heart disease (HHD), stroke, diabetes, and, as relevant selected other CVDs, after adjusting for important confounders. We pooled all data to estimate relative risks (RRs) for each risk factor and examined effect modification by age or other factors, using random effects models. Results Across all risk factors, an average of 123 cohorts provided data on 1.4 million individuals and 52,000 CVD events. Each metabolic risk factor was robustly related to CVD. At the baseline age of 55–64 years, the RR for 10 mmHg higher SBP was largest for HHD (2.16; 95% CI 2.09–2.24), followed by effects on both stroke subtypes (1.66; 1.39–1.98 for hemorrhagic stroke and 1.63; 1.57–1.69 for ischemic stroke). In the same age group, RRs for 1 mmol/L higher TC were 1.44 (1.29–1.61) for IHD and 1.20 (1.15–1.25) for ischemic stroke. The RRs for 5 kg/m2 higher BMI for ages 55–64 ranged from 2.32 (2.04–2.63) for diabetes, to 1.44 (1.40–1.48) for IHD. For 1 mmol/L higher FPG, RRs in this age group were 1.18 (1.08–1.29) for IHD and 1.14 (1.01–1.29) for total stroke. For all risk factors, proportional effects declined with age, were generally consistent by sex, and differed by region in only a few age groups for certain risk factor-disease pairs. Conclusion Our results provide robust, comparable and precise estimates of the effects of major metabolic risk factors on CVD and diabetes by age group. PMID:23935815

  12. [Type 1 diabetes mellitus: most recent advances in its pathogenesis and treatment].

    PubMed

    Zóka, András; Somogyi, Anikó; Firneisz, Gábor

    2012-07-01

    The incidence and prevalence of diabetes mellitus is globally increasing. The causes of this trend are relatively obvious in the case of type 2 diabetes. In contrast, in case of type 1 diabetes the amount of available data is continuously growing, but the causes are not so well defined. The genetic risk, especially related to the MHC genes is well known, and the increasing amount of data underlines the role of additional risks due to non-MHC genetic polimorphisms. Hopefully, they will provide the basis for future diagnostic and therapeutic approaches. There is increasing knowledge about the pathophysiological aspects including the role of immunological disregulation (balance of autotolerance, role of regulatory T-cells) and environmental triggers (nutrients, viruses). Information on the entero-insular axis and the β-cell protective role of incretin hormones might offer an opportunity for new therapeutic strategies. In this paper, the authors try to summarize some current aspects of the pathomechanism and related therapeutic approaches.

  13. [Osteoporosis in diabetes].

    PubMed

    Kumeda, Yasuro

    2008-05-01

    The diabetes is at great risk of the osteoporosis, and the bone fragility unrelated to bone density forms the pathological conditions peculiar to diabetes. The factor participating in diabetic osteoporosis has a state of insulin action deficiency, a hyperglycemic state, diabetic complications, and so on. An osteoblastic cell function is deteriorated and the number of that is decreased by the absolute and relative insulin deficiency, and sustained hyperglycemia also decreases an osteoblastic cell function still more. Furthermore, the osteoclast-related bone resorption is also promoted through sorbitol accumulation in the cell by the hyperglycemia state. The expression of transcription factors regulating osteoblastic cell differentiation is restrained, and the apoptosis of those cells is promoted. As a result, osteoplasty is obstructed. In the bone, AGEs (advanced glycation endproducts) is produced in excess, and bone fragility is promoted by the ratio of the AGEs bridging with the collagen rising. The complications of diabetes, such as visual disorder and the neuropathy, raise the risk of the fall in the diabetic osteoporosis patient, therefore, they will have more chance of fractures. PMID:18445876

  14. Relationship Between Skin Intrinsic Fluorescence—an Indicator of Advanced Glycation End Products—and Upper Extremity Impairments in Individuals With Diabetes Mellitus

    PubMed Central

    Shah, Kshamata M.; Clark, B. Ruth; McGill, Janet B.; Lang, Catherine E.; Maynard, John

    2015-01-01

    Background Accumulation of advanced glycation end products (AGEs) is thought to contribute to limited joint mobility in people with diabetes mellitus (DM), but the relationships among AGEs, shoulder structural changes, movement, and disability are not understood. Objective The purpose of this study was to determine the differences and relationships among skin intrinsic fluorescence (SIF), a proxy measure of AGEs, biceps and supraspinatus tendon thickness, upper extremity movement, and disability in groups with and without DM. Design This was a cross-sectional, case-control study. Methods Fifty-two individuals participated: 26 with type 2 DM and 26 controls matched for sex, age, and body mass index. The main outcome measures were: SIF; biceps and supraspinatus tendon thickness; 3-dimensional peak shoulder motion; and Disability of the Arm, Shoulder and Hand (DASH) questionnaire scores. Results Mean SIF measurements were 19% higher in the DM group compared with the control group (P<.05). Biceps tendons (mean and 95% confidence interval [CI]) (4.7 mm [4.4, 5.0] versus 3.2 mm [2.9, 3.5]) and supraspinatus tendons (6.4 mm [5.9, 6.8] versus 4.9 mm [4.4, 5.3]) were thicker and peak humerothoracic elevation (139° [135°, 146°] versus 150° [146°, 155°]) and glenohumeral external rotation (35° [26°, 46°] versus 51° [41°, 58°]) were reduced in the DM group compared with the control group (P<.05). In the DM group, SIF was correlated to biceps tendon thickness, DASH score, and shoulder motion (r=.44–.51, P<.05). The SIF score and shoulder strength explained 64% of the DASH scores (P<.01). Limitations Because this was a cross-sectional study design, a cause-effect relationship could not be established. Conclusions Accumulation of AGEs in the connective tissues of individuals with DM appears to be associated with increased tendon thickness and decreased shoulder joint mobility and upper extremity function. Physical therapists should be aware of these possible

  15. RECENT INCIDENCE OF TYPE 1 DIABETES MELLITUS IN MONTENEGRO: A SHIFT TOWARD YOUNGER AGE AT DISEASE ONSET.

    PubMed

    Samardžić, Mira; Martinović, Milica; Nedović-Vuković, Mirjana; Popović-Samardžić, Milena

    2016-03-01

    In the last several decades, a great number of studies have pointed to a dramatic increase of type 1 diabetes mellitus (T1DM) incidence in the whole world, especially in younger age groups. Therefore, the aim of the study was to assess changes in the age distribution at onset of T1DM in Montenegro children aged < 15 years during a 15-year period (1997-2011) and analyze the seasonal pattern. Primary case ascertainment was from diabetes register, secondary and tertiary independent data sources were hospital case records and register of children receiving free test stripes in pharmacy. Standardized incidence rates were calculated using the Poisson regression. Case ascertainment was 100% complete using the capture-recapture method. The mean age-standardized incidence was 18.6/100,000 (95% CI: 13.0-24.1) from 2007 to 2011 compared with 13.4/100,000 95% CI, 11.5-15.5) from 1997 to 2006. The incidence of T1DM increased predominantly in younger age groups. Relative increase of incidence per 5-year period was largest in boys aged 0-4 and 5-9 years: 64.7% (95% CI: 20.6-10.7; p = 0.004) and 52.8% (95% CI: 16.9-88.8; p = 0.004), respectively. Seasonality in monthly case counts of T1DM was apparent. The greatest number of cases were diagnosed during autumn and winter months. In conclusion, the onset of T1DM was found to occur at an ever younger age in Montenegro children. Our results indicated a seasonal pattern of the disease onset.

  16. RECENT INCIDENCE OF TYPE 1 DIABETES MELLITUS IN MONTENEGRO: A SHIFT TOWARD YOUNGER AGE AT DISEASE ONSET.

    PubMed

    Samardžić, Mira; Martinović, Milica; Nedović-Vuković, Mirjana; Popović-Samardžić, Milena

    2016-03-01

    In the last several decades, a great number of studies have pointed to a dramatic increase of type 1 diabetes mellitus (T1DM) incidence in the whole world, especially in younger age groups. Therefore, the aim of the study was to assess changes in the age distribution at onset of T1DM in Montenegro children aged < 15 years during a 15-year period (1997-2011) and analyze the seasonal pattern. Primary case ascertainment was from diabetes register, secondary and tertiary independent data sources were hospital case records and register of children receiving free test stripes in pharmacy. Standardized incidence rates were calculated using the Poisson regression. Case ascertainment was 100% complete using the capture-recapture method. The mean age-standardized incidence was 18.6/100,000 (95% CI: 13.0-24.1) from 2007 to 2011 compared with 13.4/100,000 95% CI, 11.5-15.5) from 1997 to 2006. The incidence of T1DM increased predominantly in younger age groups. Relative increase of incidence per 5-year period was largest in boys aged 0-4 and 5-9 years: 64.7% (95% CI: 20.6-10.7; p = 0.004) and 52.8% (95% CI: 16.9-88.8; p = 0.004), respectively. Seasonality in monthly case counts of T1DM was apparent. The greatest number of cases were diagnosed during autumn and winter months. In conclusion, the onset of T1DM was found to occur at an ever younger age in Montenegro children. Our results indicated a seasonal pattern of the disease onset. PMID:27333720

  17. Protective role of sulphoraphane against vascular complications in diabetes.

    PubMed

    Yamagishi, Sho-Ichi; Matsui, Takanori

    2016-10-01

    Context Diabetes is a global health challenge. Although large prospective clinical trials have shown that intensive control of blood glucose or blood pressure reduces the risk for development and progression of vascular complications in diabetes, a substantial number of diabetic patients still experience renal failure and cardiovascular events, which could account for disabilities and high mortality rate in these subjects. Objective Sulphoraphane is a naturally occurring isothiocyanate found in widely consumed cruciferous vegetables, such as broccoli, cabbage and Brussels sprouts, and an inducer of phase II antioxidant and detoxification enzymes with anticancer properties. We reviewed here the protective role of sulphoraphane against diabetic vascular complications. Methods In this review, literature searches were undertaken in Medline and in CrossRef. Non-English language articles were excluded. Keywords [sulphoraphane and (diabetes, diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, diabetic complications, vascular, cardiomyocytes, heart or glycation)] have been used to select the articles. Results There is accumulating evidence that sulphoraphane exerts beneficial effects on vascular damage in both cell culture and diabetic animal models via antioxidative properties. Furthermore, we have recently found that sulphoraphane inhibits in vitro formation of advanced glycation end products (AGEs), suppresses the AGE-induced inflammatory reactions in rat aorta by reducing receptor for AGEs (RAGE) expression and decreases serum levels of AGEs in humans. Conclusion These findings suggest that blockade of oxidative stress and/or the AGE-RAGE axis by sulphoraphane may be a novel therapeutic strategy for preventing vascular complications in diabetes. PMID:26841240

  18. Association of advanced age with concentrations of uraemic toxins in CKD.

    PubMed

    Rroji, Merita; Eloot, Sunny; Dhondt, Annemie; Van Biesen, Wim; Glorieux, Griet; Neirynck, Nathalie; Vandennoortgate, Nele; Liabeuf, Sophie; Massy, Ziad; Vanholder, Raymond

    2016-02-01

    To our knowledge, there are no studies on advanced chronic kidney disease (CKD) analysing the impact of ageing on serum concentrations of uraemic toxins while adjusting for renal function. Knowledge of this feature, however, could influence prognostic assessment and therapeutic decision-making, e.g. about when to start dialysis or how intensive it should be. Indeed, the slowing down of metabolism with age may result in lower uraemic toxin concentrations, hence reducing their toxic effects. In this case, a later start of dialysis or less intensive dialysis may become justified in an already fragile population that might enjoy a better quality of life without a survival disadvantage with conservative treatment. We assessed the impact of advancing age on uraemic solute concentrations [blood, urea, nitrogen (BUN), uric acid, creatinine, asymmetric and symmetric dimethylarginine (ADMA and SDMA), β2-microglobulin and a large array of protein-bound solutes] by matching 126 maintenance haemodialysis patients subdivided into two age-groups, younger vs. older (using the median as cut-off: 72 years). Concentrations were compared after age stratification and were matched with patient and dialysis characteristics. In addition, 93 non-dialysed CKD patients (median as cut-off: 70 years), with a comparable average estimated glomerular filtration rate (eGFR) between younger and older age-groups, were analysed. In haemodialysis patients, carboxy-methyl-furanpropionic acid (CMPF) levels were markedly higher and BUN and uric acid borderline lower in the older age-group. All other solutes showed no difference. At multifactor analysis, the concentration of several uraemic toxins was associated with residual renal function and protein intake in the overall haemodialysis group and the younger group, but the association with most solutes, especially those protein-bound, was lost in the older age-group. No differences were found in non-dialysed CKD patients. It was concluded that in this

  19. Age Disparity in Palliative Radiation Therapy Among Patients With Advanced Cancer

    SciTech Connect

    Wong, Jonathan; Xu, Beibei; Yeung, Heidi N.; Roeland, Eric J.; Martinez, Maria Elena; Le, Quynh-Thu; Mell, Loren K.; Murphy, James D.

    2014-09-01

    Purpose/Objective: Palliative radiation therapy represents an important treatment option among patients with advanced cancer, although research shows decreased use among older patients. This study evaluated age-related patterns of palliative radiation use among an elderly Medicare population. Methods and Materials: We identified 63,221 patients with metastatic lung, breast, prostate, or colorectal cancer diagnosed between 2000 and 2007 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Receipt of palliative radiation therapy was extracted from Medicare claims. Multivariate Poisson regression analysis determined residual age-related disparity in the receipt of palliative radiation therapy after controlling for confounding covariates including age-related differences in patient and demographic covariates, length of life, and patient preferences for aggressive cancer therapy. Results: The use of radiation decreased steadily with increasing patient age. Forty-two percent of patients aged 66 to 69 received palliative radiation therapy. Rates of palliative radiation decreased to 38%, 32%, 24%, and 14% among patients aged 70 to 74, 75 to 79, 80 to 84, and over 85, respectively. Multivariate analysis found that confounding covariates attenuated these findings, although the decreased relative rate of palliative radiation therapy among the elderly remained clinically and statistically significant. On multivariate analysis, compared to patients 66 to 69 years old, those aged 70 to 74, 75 to 79, 80 to 84, and over 85 had a 7%, 15%, 25%, and 44% decreased rate of receiving palliative radiation, respectively (all P<.0001). Conclusions: Age disparity with palliative radiation therapy exists among older cancer patients. Further research should strive to identify barriers to palliative radiation among the elderly, and extra effort should be made to give older patients the opportunity to receive this quality of life-enhancing treatment at the end

  20. Obesity and Life Expectancy with and without Diabetes in Adults Aged 55 Years and Older in the Netherlands: A Prospective Cohort Study

    PubMed Central

    Ligthart, Symen; Peeters, Anna; Hofman, Albert; Nusselder, Wilma; Franco, Oscar H.

    2016-01-01

    Background Overweight and obesity are associated with increased risk of type 2 diabetes. Limited evidence exists regarding the effect of excess weight on years lived with and without diabetes. We aimed to determine the association of overweight and obesity with the number of years lived with and without diabetes in a middle-aged and elderly population. Methods and Findings The study included 6,499 individuals (3,656 women) aged 55 y and older from the population-based Rotterdam Study. We developed a multistate life table to calculate life expectancy for individuals who were normal weight, overweight, and obese and the difference in years lived with and without diabetes. For life table calculations, we used prevalence, incidence rate, and hazard ratios (HRs) for three transitions (healthy to diabetes, healthy to death, and diabetes to death), stratifying by body mass index (BMI) at baseline and adjusting for confounders. During a median follow-up of 11.1 y, we observed 697 incident diabetes events and 2,192 overall deaths. Obesity was associated with an increased risk of developing diabetes (HR: 2.13 [p < 0.001] for men and 3.54 [p < 0.001] for women). Overweight and obesity were not associated with mortality in men and women with or without diabetes. Total life expectancy remained unaffected by overweight and obesity. Nevertheless, men with obesity aged 55 y and older lived 2.8 (95% CI −6.1 to −0.1) fewer y without diabetes than normal weight individuals, whereas, for women, the difference between obese and normal weight counterparts was 4.7 (95% CI −9.0 to −0.6) y. Men and women with obesity lived 2.8 (95% CI 0.6 to 6.2) and 5.3 (95% CI 1.6 to 9.3) y longer with diabetes, respectively, compared to their normal weight counterparts. Since the implications of these findings could be limited to middle-aged and older white European populations, our results need confirmation in other populations. Conclusions Obesity in the middle aged and elderly is associated

  1. Age-Period-Cohort Analysis of 1990–2003 Incidence Time Trends of Childhood Diabetes in Italy

    PubMed Central

    Bruno, Graziella; Maule, Milena; Merletti, Franco; Novelli, Giulia; Falorni, Alberto; Iannilli, Antonio; Iughetti, Lorenzo; Altobelli, Emma; d'Annunzio, Giuseppe; Piffer, Silvano; Pozzilli, Paolo; Iafusco, Dario; Songini, Marco; Roncarolo, Federico; Toni, Sonia; Carle, Flavia; Cherubini, Valentino

    2010-01-01

    OBJECTIVE To investigate age-period-cohort effects on the temporal trend of type 1 diabetes in children age 0–14 years in Italian registries. RESEARCH DESIGN AND METHODS This report is based on 5,180 incident cases in the period 1990–2003 from the Registry for Type 1 Diabetes Mellitus in Italy (RIDI). Multilevel (random intercept) Poisson regression models were used to model the effects of sex, age, calendar time, and birth cohorts on temporal trends, taking into account the registry-level variance component. RESULTS The incidence rate was 12.26 per 100,000 person-years and significantly higher in boys (13.13 [95% CI 12.66–13.62]) than in girls (11.35 [10.90–11.82]). Large geographical variations in incidence within Italy were evident; incidence was highest in Sardinia, intermediate in Central-Southern Italy, and high in Northern Italy, particularly in the Trento Province, where the incidence rate was 18.67 per 100,000 person-years. An increasing temporal trend was evident (2.94% per year [95% CI 2.22–3.67]). With respect to the calendar period 1990–1992, the incidence rates increased linearly by 15, 27, 35, and 40% in the following time periods (P for trend < 0.001). With respect to the 1987–1993 birth cohort, the incidence rate ratio increased approximately linearly from 0.63 (95% CI 0.54–0.73) in the 1975–1981 cohort to 1.38 (1.06–1.80) in the 1999–2003 cohort. The best model, however, included sex, age, and a linear time trend (drift). CONCLUSIONS Large geographical variations and an increasing temporal trend in diabetes incidence are evident among type 1 diabetic children in Italy. Age-period-cohort analysis shows that the variation over time has a linear component that cannot be ascribed to either the calendar period or the birth cohort. PMID:20566665

  2. Recent advances in the use of metformin: can treating diabetes prevent breast cancer?

    PubMed

    Hatoum, Diana; McGowan, Eileen M

    2015-01-01

    There is substantial epidemiological evidence pointing to an increased incidence of breast cancer and morbidity in obese, prediabetic, and diabetic patients. In vitro studies strongly support metformin, a diabetic medication, in breast cancer therapy. Although metformin has been heralded as an exciting new breast cancer treatment, the principal consideration is whether metformin can be used as a generic treatment for all breast cancer types. Importantly, will metformin be useful as an inexpensive therapy for patients with comorbidity of diabetes and breast cancer? In general, meta-analyses of clinical trial data from retrospective studies in which metformin treatment has been used for patients with diabetes and breast cancer have a positive trend; nevertheless, the supporting clinical data outcomes remain inconclusive. The heterogeneity of breast cancer, confounded by comorbidity of disease in the elderly population, makes it difficult to determine the actual benefits of metformin therapy. Despite the questionable evidence available from observational clinical studies and meta-analyses, randomized phases I-III clinical trials are ongoing to test the efficacy of metformin for breast cancer. This special issue review will focus on recent research, highlighting in vitro research and retrospective observational clinical studies and current clinical trials on metformin action in breast cancer. PMID:25866793

  3. Recent advances in understanding the anti-diabetic actions of dietary flavonoids.

    PubMed

    Babu, Pon Velayutham Anandh; Liu, Dongmin; Gilbert, Elizabeth R

    2013-11-01

    Flavonoids are polyphenolic compounds that are abundant in fruits and vegetables, and increasing evidence demonstrates a positive relationship between consumption of flavonoid-rich foods and disease prevention. Epidemiological, in vitro and animal studies support the beneficial effects of dietary flavonoids on glucose and lipid homeostasis. It is encouraging that the beneficial effects of some flavonoids are at physiological concentrations and comparable to clinically-used anti-diabetic drugs; however, clinical research in this field and studies on the anti-diabetic effects of flavonoid metabolites are limited. Flavonoids act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, hepatocytes, adipocytes and skeletal myofibers. Flavonoids may exert beneficial effects in diabetes by (i) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (ii) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (iii) reducing insulin resistance, inflammation and oxidative stress in muscle and fat and (iv) increasing glucose uptake in skeletal muscle and white adipose tissue. This review highlights recent findings on the anti-diabetic effects of dietary flavonoids, including flavan-3-ols, flavanones, flavonols, anthocyanidins, flavones and isoflavones, with particular emphasis on the studies that investigated the cellular and molecular mechanisms involved in the beneficial effects of the compounds.

  4. Recent advances in understanding the anti-diabetic actions of dietary flavonoids

    PubMed Central

    Babu, Pon Velayutham Anandh; Liu, Dongmin; Gilbert, Elizabeth R.

    2013-01-01

    Flavonoids are polyphenolic compounds that are abundant in fruits and vegetables and increasing evidence demonstrates a positive relationship between consumption of flavonoid-rich foods and disease prevention. Epidemiological, in vitro and animal studies support the beneficial effects of dietary flavonoids on glucose and lipid homeostasis. It is encouraging that the beneficial effects of some flavonoids are at physiological concentrations and comparable to clinically-used anti-diabetic drugs; however, clinical research in this field and studies on the anti-diabetic effects of flavonoid metabolites are limited. Flavonoids act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, hepatocytes, adipocytes, and skeletal myofibers. Flavonoids may exert beneficial effects in diabetes by (i) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells, (ii) improving hyperglycemia through regulation of glucose metabolism in hepatocytes, (iii) reducing insulin resistance, inflammation and oxidative stress in muscle and fat, and (iv) increasing glucose uptake in skeletal muscle and white adipose tissue. This review highlights recent findings on the anti-diabetic effects of dietary flavonoids, including flavan-3-ols, flavanones, flavonols, anthocyanidins, flavones, and isoflavones, with particular emphasis on the studies that investigated the cellular and molecular mechanisms involved in the beneficial effects of the compounds. PMID:24029069

  5. Patient-provider communication and trust in relation to use of an online patient portal among diabetes patients: The Diabetes and Aging Study.

    PubMed

    Lyles, Courtney R; Sarkar, Urmimala; Ralston, James D; Adler, Nancy; Schillinger, Dean; Moffet, Howard H; Huang, Elbert S; Karter, Andrew J

    2013-01-01

    Patient-provider relationships influence diabetes care; less is known about their impact on online patient portal use. Diabetes patients rated provider communication and trust. In this study, we linked responses to electronic medical record data on being a registered portal user and using secure messaging (SM). We specified regression models to evaluate main effects on portal use, and subgroup analyses by race/ethnicity and age. 52% of subjects were registered users; among those, 36% used SM. Those reporting greater trust were more likely to be registered users (relative  risk (RR)=1.14) or SM users (RR=1.29). In subgroup analyses, increased trust was associated with being a registered user among white, Latino, and older patients, as well as SM use among white patients. Better communication ratings were also related to being a registered user among older patients. Since increased trust and communication were associated with portal use within subgroups, this suggests that patient-provider relationships encourage portal engagement.

  6. Successful aging: Advancing the science of physical independence in older adults.

    PubMed

    Anton, Stephen D; Woods, Adam J; Ashizawa, Tetso; Barb, Diana; Buford, Thomas W; Carter, Christy S; Clark, David J; Cohen, Ronald A; Corbett, Duane B; Cruz-Almeida, Yenisel; Dotson, Vonetta; Ebner, Natalie; Efron, Philip A; Fillingim, Roger B; Foster, Thomas C; Gundermann, David M; Joseph, Anna-Maria; Karabetian, Christy; Leeuwenburgh, Christiaan; Manini, Todd M; Marsiske, Michael; Mankowski, Robert T; Mutchie, Heather L; Perri, Michael G; Ranka, Sanjay; Rashidi, Parisa; Sandesara, Bhanuprasad; Scarpace, Philip J; Sibille, Kimberly T; Solberg, Laurence M; Someya, Shinichi; Uphold, Connie; Wohlgemuth, Stephanie; Wu, Samuel Shangwu; Pahor, Marco

    2015-11-01

    The concept of 'successful aging' has long intrigued the scientific community. Despite this long-standing interest, a consensus definition has proven to be a difficult task, due to the inherent challenge involved in defining such a complex, multi-dimensional phenomenon. The lack of a clear set of defining characteristics for the construct of successful aging has made comparison of findings across studies difficult and has limited advances in aging research. A consensus on markers of successful aging is furthest developed is the domain of physical functioning. For example, walking speed appears to be an excellent surrogate marker of overall health and predicts the maintenance of physical independence, a cornerstone of successful aging. The purpose of the present article is to provide an overview and discussion of specific health conditions, behavioral factors, and biological mechanisms that mark declining mobility and physical function and promising interventions to counter these effects. With life expectancy continuing to increase in the United States and developed countries throughout the world, there is an increasing public health focus on the maintenance of physical independence among all older adults. PMID:26462882

  7. Ameliorating Effect of Akebia quinata Fruit Extracts on Skin Aging Induced by Advanced Glycation End Products

    PubMed Central

    Shin, Seoungwoo; Son, Dahee; Kim, Minkyung; Lee, Seungjun; Roh, Kyung-Baeg; Ryu, Dehun; Lee, Jongsung; Jung, Eunsun; Park, Deokhoon

    2015-01-01

    The accumulation of free radicals and advanced glycation end products (AGEs) in the skin plays a very important role in skin aging. Both are known to interact with each other. Therefore, natural compounds or extracts that possess both antioxidant and antiglycation activities might have great antiageing potential. Akebia quinata fruit extract (AQFE) has been used to treat urinary tract inflammatory disease in traditional Korean and Chinese medicines. In the present study, AQFE was demonstrated to possess antioxidant and antiglycation activity. AQFE protects human dermal fibroblasts (HDFs) from oxidative stress and inhibits cellular senescence induced by oxidative stress. We also found that AQFE inhibits glycation reaction between BSA and glucose. The antiglycation activity of AQFE was dose-dependent. In addition, the antiglycation activity of AQFE was confirmed in a human skin explant model. AQFE reduced CML expression and stimulated fibrillin-1 expression in comparison to the methyglyoxal treatment. In addition, the possibility of the extract as an anti-skin aging agent has also been clinically validated. Our analysis of the crow’s feet wrinkle showed that there was a decrease in the depth of deep furrows in RI treated with AQFE cream over an eight-week period. The overall results suggest that AQFE may work as an anti-skin aging agent by preventing oxidative stress and other complications associated with AGEs formation. PMID:26569300

  8. Ameliorating Effect of Akebia quinata Fruit Extracts on Skin Aging Induced by Advanced Glycation End Products.

    PubMed

    Shin, Seoungwoo; Son, Dahee; Kim, Minkyung; Lee, Seungjun; Roh, Kyung-Baeg; Ryu, Dehun; Lee, Jongsung; Jung, Eunsun; Park, Deokhoon

    2015-11-12

    The accumulation of free radicals and advanced glycation end products (AGEs) in the skin plays a very important role in skin aging. Both are known to interact with each other. Therefore, natural compounds or extracts that possess both antioxidant and antiglycation activities might have great antiageing potential. Akebia quinata fruit extract (AQFE) has been used to treat urinary tract inflammatory disease in traditional Korean and Chinese medicines. In the present study, AQFE was demonstrated to possess antioxidant and antiglycation activity. AQFE protects human dermal fibroblasts (HDFs) from oxidative stress and inhibits cellular senescence induced by oxidative stress. We also found that AQFE inhibits glycation reaction between BSA and glucose. The antiglycation activity of AQFE was dose-dependent. In addition, the antiglycation activity of AQFE was confirmed in a human skin explant model. AQFE reduced CML expression and stimulated fibrillin-1 expression in comparison to the methyglyoxal treatment. In addition, the possibility of the extract as an anti-skin aging agent has also been clinically validated. Our analysis of the crow's feet wrinkle showed that there was a decrease in the depth of deep furrows in RI treated with AQFE cream over an eight-week period. The overall results suggest that AQFE may work as an anti-skin aging agent by preventing oxidative stress and other complications associated with AGEs formation.

  9. Extracellular superoxide dismutase deficiency impairs wound healing in advanced age by reducing neovascularization and fibroblast function

    PubMed Central

    Fujiwara, Toshihiro; Duscher, Dominik; Rustad, Kristine C.; Kosaraju, Revanth; Rodrigues, Melanie; Whittam, Alexander J.; Januszyk, Michael; Maan, Zeshaan N.; Gurtner, Geoffrey C.

    2016-01-01

    Advanced age is characterized by impairments in wound healing, and evidence is accumulating that this may be due in part to a concomitant increase in oxidative stress. Extended exposure to reactive oxygen species (ROS) is thought to lead to cellular dysfunction and organismal death via the destructive oxidation of intra-cellular proteins, lipids and nucleic acids. Extracellular superoxide dismutase (ecSOD/SOD3) is a prime antioxidant enzyme in the extracellular space that eliminates ROS. Here, we demonstrate that reduced SOD3 levels contribute to healing impairments in aged mice. These impairments include delayed wound closure, reduced neovascularization, impaired fibroblast proliferation and increased neutrophil recruitment. We further establish that SOD3 KO and aged fibroblasts both display reduced production of TGF-β1, leading to decreased differentiation of fibroblasts into myofibroblasts. Taken together, these results suggest that wound healing impairments in ageing are associated with increased levels of ROS, decreased SOD3 expression and impaired extracellular oxidative stress regulation. Our results identify SOD3 as a possible target to correct age-related cellular dysfunction in wound healing. PMID:26663425

  10. Driving with diabetes: precaution, not prohibition, is the proper approach.

    PubMed

    Kohrman, Daniel B

    2013-03-01

    Safety issues posed by driving with diabetes are primarily related to severe hypoglycemia, yet some public authorities rely on categorical restrictions on drivers with diabetes. This approach is misguided. Regulation of all drivers with diabetes, or all drivers using insulin, ignores the diversity of people with diabetes and fails to focus on the subpopulation posing the greatest risk. Advances in diabetes care technology and understanding of safety consequences of diabetes have expanded techniques available to limit risks of driving with diabetes. New means of insulin administration and blood glucose monitoring offer greater ease of anticipating and preventing hypoglycemia, and thus, limit driving risk for persons with diabetes. So too do less sophisticated steps taken by people with diabetes and the health care professionals they consult. These include adoption and endorsement of safety-sensitive behaviors, such as testing before a drive and periodic testing on longer trips. Overall, and in most individual cases, driving risks for persons with diabetes are less than those routinely tolerated by our society. Examples include freedom to drive in dangerous conditions and lax regulation of drivers in age and medical cohorts with elevated overall rates of driving mishaps. Data linking specific diabetes symptoms or features with driving risk are quite uncertain. Hence, there is much to recommend: a focus on technological advances, human precautions, and identifying individuals with diabetes with a specific history of driving difficulty. By contrast, available evidence does not support unfocused regulation of all or most drivers with diabetes.

  11. Earlier Age of Onset of Chronic Hypertension and Type 2 Diabetes Mellitus After a Hypertensive Disorder of Pregnancy or Gestational Diabetes Mellitus.

    PubMed

    Heida, Karst Y; Franx, Arie; van Rijn, Bas B; Eijkemans, Marinus J C; Boer, Jolanda M A; Verschuren, Monique W M; Oudijk, Martijn A; Bots, Michiel L; van der Schouw, Yvonne T

    2015-12-01

    A prospective cohort study was conducted to assess the impact of a history of hypertensive disorder of pregnancy (HDP) or gestational diabetes mellitus (GDM) on the risk and age of onset of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease (CVD) later in life, independent of hypertension and T2D. Between 1993 and 1997, 22 265 ever-pregnant women were included from the European Prospective Investigation into Cancer and Nutrition-NL study, aged 20 to 70 years at baseline. Details on complications of pregnancy and known hypertension were obtained by questionnaire. Blood pressure was measured at enrollment. Participants were followed for the occurrence of CVD events. Data were analyzed using ANCOVA, multivariable logistic regression, and Cox proportional hazard (with HDP and GDM as time-dependent variables for T2D and CVD) models. At enrollment, women with a HDP reported diagnosis of hypertension 7.7 years earlier (95% confidence interval [CI] 6.9-8.5) and women with GDM reported diagnosis of T2D 7.7 years earlier (95% CI 5.8-9.6) than women without pregnancy complications. After adjustment for potential confounders, HDP was associated with presence of hypertension at enrollment (odds ratio 2.12, 95% CI 1.98-2.28) and onset of CVD later in life (hazard ratio 1.21, 95% CI 1.10-1.32). After including the intermediates hypertension and T2D in the model, the risk of CVD later in life decreased (hazard ratio 1.09, 95% CI 1.00-1.20). GDM was associated with an increased risk of developing T2D later in life (hazard ratio 3.68, 95% CI 2.77-4.90), but not with risk of CVD. HDP and GDM have a substantial impact on the risk of CVD and are potentially important indicators for preventive cardiovascular risk management.

  12. Association between age at menarche and diabetes in Korean post-menopausal women: results from the Korea National Health and Nutrition Examination Survey (2007-2009).

    PubMed

    Hwang, Eunjung; Lee, Kyong Won; Cho, Yoonsu; Chung, Hye Kyung; Shin, Min-Jeong

    2015-01-01

    Early menarche is known to be associated with diabetes, however this association remains controversial. Our study aimed to investigate the possible association between age at menarche and diabetes prevalence in post-menopausal Korean women. This study included 3,254 post-menopausal Korean women aged 50-85 years from the Korea National Health and Nutrition Examination Survey IV (KNHANES 2007-2009). Logistic regression analyses were used to estimate odds ratios (ORs) for diabetes prevalence. Levels of biochemical markers were compared according to groups by age at menarche. Women in the earlier menarche age group (10-12 years) showed higher levels of fasting blood glucose (FBG) and scores of homeostatic model assessment in the insulin resistance (HOMA-IR) index than other groups (p <0.05). After adjusting for potential confounding factors, early age at menarche was significantly associated with a higher prevalence of diabetes (OR 1.86, 95% confidence intervals [CI] 1.07-3.23). The observed association remained significant despite additional adjustment for body mass index and waist circumference (OR 1.82, 95% CI 1.03-3.23) and despite further adjustments for FBG levels and HOMA-IR index (OR 2.25, 95% CI 1.11-4.55). Our findings strengthen the hypothesis that younger age at menarche is associated with increased diabetes prevalence in the Korean population.

  13. Risk Factors for Macro- and Microvascular Complications among Older Adults with Diagnosed Type 2 Diabetes: Findings from The Irish Longitudinal Study on Ageing

    PubMed Central

    McHugh, Sheena M.; Fitzgerald, Anthony P.; Buckley, Claire M.; Canavan, Ronan J.

    2016-01-01

    Objective. To explore risk factors for macro- and microvascular complications in a nationally representative sample of adults aged 50 years and over with type 2 diabetes in Ireland. Methods. Data from the first wave of The Irish Longitudinal Study on Ageing (TILDA) (2009–2011) was used in cross-sectional analysis. The presence of doctor diagnosis of diabetes, risk factors, and macro- and microvascular complications were determined by self-report. Gender-specific differences in risk factor prevalence were assessed with the chi-squared test. Binomial regression analysis was conducted to explore independent associations between established risk factors and diabetes-related complications. Results. Among 8175 respondents, 655 were classified as having type 2 diabetes. Older age, being male, a history of smoking, a lower level of physical activity, and a diagnosis of high cholesterol were independent predictors of macrovascular complications. Diabetes diagnosis of 10 or more years, a history of smoking, and a diagnosis of hypertension were associated with an increased risk of microvascular complications. Older age, third-level education, and a high level of physical activity were protective factors (p < 0.05). Conclusions. Early intervention to target modifiable risk factors is urgently needed to reduce diabetes-related morbidity in the older population in Ireland. PMID:27294152

  14. Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic β-Cell Mass in Middle-Aged Obese Diabetic Mice

    PubMed Central

    Alkhalidy, Hana; Moore, William; Zhang, Yanling; Wang, Aihua; Ali, Mostafa; Suh, Kyung-Shin; Zhen, Wei; Cheng, Zhiyong; Jia, Zhenquan; Hulver, Matthew

    2015-01-01

    Insulin resistance and a progressive decline in functional β-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significantly ameliorated hyperglycemia, hyperinsulinemia, and circulating lipid profile, which were associated with the improved peripheral insulin sensitivity in middle-aged obese mice fed a high-fat (HF) diet. Kaempferol treatment reversed HF diet impaired glucose transport-4 (Glut4) and AMP-dependent protein kinase (AMPK) expression in both muscle and adipose tissues from obese mice. In vitro, kaempferol increased lipolysis and prevented high fatty acid-impaired glucose uptake, glycogen synthesis, AMPK activity, and Glut4 expression in skeletal muscle cells. Using another mouse model of T2D generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved islet β-cell mass. These results demonstrate that kaempferol may be a naturally occurring anti-diabetic agent by improving peripheral insulin sensitivity and protecting against pancreatic β-cell dysfunction. PMID:26064984

  15. Learning to bypass the central bottleneck: declining automaticity with advancing age.

    PubMed

    Maquestiaux, François; Laguë-Beauvais, Maude; Ruthruff, Eric; Hartley, Alan; Bherer, Louis

    2010-03-01

    Does advancing age reduce the ability to bypass the central bottleneck through task automatization? To answer this question, the authors asked 12 older adults and 20 young adults to first learn to perform an auditory-vocal task (low vs. high pitch) in 6 single-task sessions. Their dual-task performance was then assessed with a psychological refractory period paradigm, in which the highly practiced auditory-vocal task was presented as Task 2, along with an unpracticed visual-manual Task 1. Converging evidence indicated qualitative differences in dual-task performance with age: Whereas the vast majority of young adults bypassed the bottleneck, at most 1 of the 12 older adults was able to do so. Older adults are either reluctant to bypass the bottleneck (as a matter of strategy) or have lost the ability to automatize task performance. PMID:20230138

  16. Habitual sugar intake and cognitive function among middle-aged and older Puerto Ricans without diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Intake of added sugars, mainly fructose and sucrose, has been associated with risk factors for cognitive impairment, such as obesity, the metabolic syndrome and type 2 diabetes. The objective of this analysis was to examine whether habitual intakes of total sugars, added sugars, sugar-sweetened bev...

  17. Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, attenuates diabetes-induced renal damage through the advanced glycation end product-related pathway in db/db mice.

    PubMed

    Park, Chan Hum; Yokozawa, Takako; Noh, Jeong Sook

    2014-08-01

    This study was conducted to examine whether oligonol, a low-molecular-weight polyphenol derived from lychee fruit, has an ameliorative effect on diabetes-induced alterations, such as advanced glycation end product (AGE) formation or apoptosis in the kidneys of db/db mice with type 2 diabetes. Oligonol [10 or 20 mg/(kg body weight · d), orally] was administered every day for 8 wk to prediabetic db/db mice, and its effect was compared with vehicle-treated db/db and normal control mice (m/m). The administration of oligonol decreased the elevated renal glucose concentrations and reactive oxygen species in db/db mice (P < 0.05). The increased serum urea nitrogen and creatinine concentrations, which reflect renal dysfunction in db/db mice, were substantially lowered by oligonol. Oligonol reduced renal protein expression of NAD(P)H oxidase subunits (p22 phagocytic oxidase and NAD(P)H oxidase-4), AGEs (except for pentosidine), and c-Jun N-terminal kinase B-targeting proinflammatory tumor necrosis factor-α (P < 0.05). Oligonol improved the expressions of antiapoptotic [B-cell lymphoma protein 2 (Bcl-2) and survivin] and proapoptotic [Bcl-2-associated X protein, cytochrome c, and caspase-3] proteins in the kidneys of db/db mice (P < 0.05). In conclusion, these results provide important evidence that oligonol exhibits a pleiotropic effect on AGE formation and apoptosis-related variables, representing renoprotective effects against the development of diabetic complications in db/db mice with type 2 diabetes.

  18. Effects of Age, Gender, BMI, and Anatomical Site on Skin Thickness in Children and Adults with Diabetes

    PubMed Central

    Derraik, José G. B.; Rademaker, Marius; Cutfield, Wayne S.; Pinto, Teresa E.; Tregurtha, Sheryl; Faherty, Ann; Peart, Jane M.; Drury, Paul L.; Hofman, Paul L.

    2014-01-01

    Objective We aimed to assess the effects of age, sex, body mass index (BMI), and anatomical site on skin thickness in children and adults with diabetes. Methods We studied 103 otherwise healthy children and adolescents with type 1 diabetes aged 5–19 years, and 140 adults with type 1 and type 2 diabetes aged 20–85 years. The thicknesses of both the dermis and subcutis were assessed using ultrasound with a linear array transducer, on abdominal and thigh skin. Results There was an age-related thickening of both dermis (p<0.0001) and subcutis (p = 0.013) in children and adolescents. Girls displayed a substantial pubertal increase in subcutis of the thigh (+54%; p = 0.048) and abdomen (+68%; p = 0.009). Adults showed an age-related decrease in dermal (p = 0.021) and subcutis (p = 0.009) thicknesses. Pubertal girls had a thicker subcutis than pubertal boys in both thigh (16.7 vs 7.5 mm; p<0.0001) and abdomen (16.7 vs 8.8 mm; p<0.0001). Men had greater thigh dermal thickness than women (1.89 vs 1.65 mm; p = 0.003), while the subcutis was thicker in women in thigh (21.3 vs 17.9 mm; p = 0.012) and abdomen (17.7 vs 9.8 mm; p<0.0001). In boys, men, and women, both dermis and subcutis were thicker on the abdomen compared to thigh; in girls this was only so for dermal thickness. In both children and adults, the skin (dermis and subcutis) became steadily thicker with increasing BMI (p<0.0001). Conclusions Skin thickness is affected by age, pubertal status, gender, BMI, and anatomical site. Such differences may be important when considering appropriate sites for dermal/subcutaneous injections and other transdermal delivery systems. PMID:24466182

  19. Recent Advances in Nanotechnology-Based Diagnosis and Treatments of Diabetes.

    PubMed

    Rao, Pasupuleti Visweswara; Gan, Siew Hua

    2015-01-01

    Nanotechnology is a field encompassing nanostructures, nanomaterials and nanoparticles, which are of increasing importance to researchers and industrial players alike. Nanotechnology addresses the construction and consumption of substances and devices on the nanometer scale. Nanomedicine is a new field that combines nanotechnology with medicine to boost human health care. Nanomedicine is an interdisciplinary field that includes various areas of biology, chemistry, physics and engineering. The most important problems related to diabetes management, such as self-monitoring of blood glucose levels and insulin injections, can now be conquered due to progress in nanomedicine, which offers glucose nanosensors, the layer-by-layer technique, carbon nanotubes, quantum dots, oral insulins, microspheres, artificial pancreases and nanopumps. In this review, the key methodological and scientific characteristics of nanomedicine related to diabetes treatment, glucose monitoring and insulin administration are discussed.

  20. Diabetes treatment in 2025: can scientific advances keep pace with prevalence?

    PubMed Central

    2012-01-01

    Despite the known benefits of a healthy lifestyle, many individuals find it hard to maintain such a lifestyle in our modern world, which facilitates sedentary behavior and overeating. As a consequence, the prevalence of type 2 diabetes mellitus is predicted to increase dramatically over the coming years. Will developments in treatments be able to counteract the resulting impact on morbidity and mortality? The various lines of research can be grouped into three main categories: technological, biological, and pharmacological. Technological solutions are focused on the delivery of insulin and glucagon via an artificial pancreas, and components of the system are already in use, suggesting this option may well be available within the next 10 years. Of the biological solutions, pancreas transplants seem unlikely to be used widely, and islet cell transplants have also been hampered by a lack of appropriate donor tissue and graft survival after transplant. However, significant progress has been made in these areas, and additional research suggests manipulating other cell types to replace beta cells may be a viable option in the longer term. The last category, pharmacological research, appears the most promising for significantly reducing the burden of type 2 diabetes mellitus. In recent years, research has concentrated on reducing blood glucose, and the increasing pace of research has been reflected in a growing number of antidiabetic agents. In the past few years, studies of the complementary approach of protecting cells from the damaging effects of high blood glucose have also been reported, as has research into the control of energy intake and energy expenditure. Evidence from studies of dietary restriction and bariatric surgery suggests it may be possible to reset metabolism to effectively cure diabetes, and research into pharmacological agents that could selectively restore energy balance is currently the most exciting prospect for future treatments for people with

  1. Advanced glycation end product 3 (AGE3) suppresses the mineralization of mouse stromal ST2 cells and human mesenchymal stem cells by increasing TGF-β expression and secretion.

    PubMed

    Notsu, Masakazu; Yamaguchi, Toru; Okazaki, Kyoko; Tanaka, Ken-ichiro; Ogawa, Noriko; Kanazawa, Ippei; Sugimoto, Toshitsugu

    2014-07-01

    In diabetic patients, advanced glycation end products (AGEs) cause bone fragility because of deterioration of bone quality. We previously showed that AGEs suppressed the mineralization of mouse stromal ST2 cells. TGF-β is abundant in bone, and enhancement of its signal causes bone quality deterioration. However, whether TGF-β signaling is involved in the AGE-induced suppression of mineralization during the osteoblast lineage remains unknown. We therefore examined the roles of TGF-β in the AGE-induced suppression of mineralization of ST2 cells and human mesenchymal stem cells. AGE3 significantly (P < .001) inhibited mineralization in both cell types, whereas transfection with small interfering RNA for the receptor for AGEs (RAGEs) significantly (P < .05) recovered this process in ST2 cells. AGE3 increased (P < .001) the expression of TGF-β mRNA and protein, which was partially antagonized by transfection with RAGE small interfering RNA. Treatment with a TGF-β type I receptor kinase inhibitor, SD208, recovered AGE3-induced decreases in osterix (P < .001) and osteocalcin (P < .05) and antagonized the AGE3-induced increase in Runx2 mRNA expression in ST2 cells (P < .001). Moreover, SD208 completely and dose dependently rescued AGE3-induced suppression of mineralization in both cell types. In contrast, SD208 intensified AGE3-induced suppression of cell proliferation as well as AGE3-induced apoptosis in proliferating ST2 cells. These findings indicate that, after cells become confluent, AGE3 partially inhibits the differentiation and mineralization of osteoblastic cells by binding to RAGE and increasing TGF-β expression and secretion. They also suggest that TGF-β adversely affects bone quality not only in primary osteoporosis but also in diabetes-related bone disorder.

  2. Plain-water intake and risk of type 2 diabetes in young and middle-aged women1234

    PubMed Central

    Pan, An; Malik, Vasanti S; Schulze, Matthias B; Manson, JoAnn E; Willett, Walter C

    2012-01-01

    Background: The replacement of caloric beverages such as sugar-sweetened beverages (SSBs) and fruit juices with noncaloric beverages such as plain water has been recommended for diabetes prevention. Objective: We evaluated the relation of plain-water intake and the substitution of plain water for SSBs and fruit juices with incident type 2 diabetes (T2D) in US women. Design: We prospectively followed 82,902 women in the Nurses’ Health Study II who were free of diabetes, cardiovascular disease, or cancer at baseline. Diet, including various beverages, was assessed by using validated food-frequency questionnaires and updated every 4 y. Incident T2D was confirmed by using a validated supplementary questionnaire. We used a 4-y lagged analysis to minimize reverse causation (ie, increased water consumption that was due to early stage of diabetes). Results: During 1,115,427 person-years of follow-up, we documented 2718 incident T2D cases. Plain-water intake was not associated with T2D risk in the multivariable-adjusted model that included age, BMI, diet, and lifestyle factors; RRs (95% CIs) across categories (<1, 1, 2–3, 4–5, and ≥6 cups/d) were 1.00, 0.93 (0.82, 1.05), 0.93 (0.83, 1.05), 1.09 (0.96, 1.24), and 1.06 (0.91, 1.23), respectively (P-trend = 0.15). We estimated that the replacement of 1 serving SSBs and fruit juices/d by 1 cup plain water/d was associated with 7% (3%, 11%) and 8% (2%, 13%) lower risk of T2D, respectively. Conclusions: Plain-water intake, per se, was not significantly associated with risk of T2D. However, substitution of plain water for SSBs or fruit juices was estimated to be associated with modestly lower risk of T2D. PMID:22552035

  3. Successful Aging: Advancing the Science of Physical Independence in Older Adults

    PubMed Central

    Anton, Stephen D.; Woods, Adam J.; Ashizawa, Tetso; Barb, Diana; Buford, Thomas W.; Carter, Christy S.; Clark, David J.; Cohen, Ronald A.; Corbett, Duane B.; Cruz-Almeida, Yenisel; Dotson, Vonetta; Ebner, Natalie; Efron, Philip A.; Fillingim, Roger B.; Foster, Thomas C.; Gundermann, David M.; Joseph, Anna-Maria; Karabetian, Christy; Leeuwenburgh, Christiaan; Manini, Todd M.; Marsiske, Michael; Mankowski, Robert T.; Mutchie, Heather L.; Perri, Michael G.; Ranka, Sanjay; Rashidi, Parisa; Sandesara, Bhanuprasad; Scarpace, Philip J.; Sibille, Kimberly T.; Solberg, Laurence M.; Someya, Shinichi; Uphold, Connie; Wohlgemuth, Stephanie; Wu, Samuel Shangwu; Pahor, Marco

    2015-01-01

    The concept of ‘Successful Aging’ has long intrigued the scientific community. Despite this long-standing interest, a consensus definition has proven to be a difficult task, due to the inherent challenge involved in defining such a complex, multi-dimensional phenomenon. The lack of a clear set of defining characteristics for the construct of successful aging has made comparison of findings across studies difficult and has limited advances in aging research. The domain in which consensus on markers of successful aging is furthest developed is the domain of physical functioning. For example, walking speed appears to be an excellent surrogate marker of overall health and predicts the maintenance of physical independence, a cornerstone of successful aging. The purpose of the present article is to provide an overview and discussion of specific health conditions, behavioral factors, and biological mechanisms that mark declining mobility and physical function and promising interventions to counter these effects. With life expectancy continuing to increase in the United States and developed countries throughout the world, there is an increasing public health focus on the maintenance of physical independence among all older adults. PMID:26462882

  4. Biological Effects Induced by Specific Advanced Glycation End Products in the Reconstructed Skin Model of Aging.

    PubMed

    Pageon, Hervé; Zucchi, Hélène; Dai, Zhenyu; Sell, David R; Strauch, Christopher M; Monnier, Vincent M; Asselineau, Daniel

    2015-01-01

    Advanced glycation end products (AGEs) accumulate in the aging skin. To understand the biological effects of individual AGEs, skin reconstructed with collagen selectively enriched with N(ɛ)-(carboxymethyl)-lysine (CML), N(ɛ)-(carboxyethyl)-lysine (CEL), methylglyoxal hydroimidazolone (MG-H1), or pentosidine was studied. Immunohistochemistry revealed increased expression of α6 integrin at the dermal epidermal junction by CEL and CML (p<0.01). Laminin 5 was diminished by CEL and MG-H1 (p<0.05). Both CML and CEL induced a robust increase (p<0.01) in procollagen I. In the culture medium, IL-6, VEGF, and MMP1 secretion were significantly decreased (p<0.05) by MG-H1. While both CEL and CML decreased MMP3, only CEL decreased IL-6 and TIMP1, while CML stimulated TIMP1 synthesis significantly (p<0.05). mRNA expression studies using qPCR in the epidermis layer showed that CEL increased type 7 collagen (COL7A1), β1, and α6 integrin, while CML increased only COL7A1 (p<0.05). MG-H1-modified collagen had no effect. Importantly, in the dermis layer, MMP3 mRNA expression was increased by both CML and MG-H1. CML also significantly increased the mRNAs of MMP1, TIMP1, keratinocyte growth factor (KGF), IL-6, and monocyte chemoattractant protein 1 (MCP1) (p<0.05). Mixed effects were present in CEL-rich matrix. Minimally glycoxidized pentosidine-rich collagen suppressed most mRNAs of the genes studied (p<0.05) and decreased VEGF and increased MCP1 protein expression. Taken together, this model of the aging skin suggests that a combination of AGEs tends to counterbalance and thus minimizes the detrimental biological effects of individual AGEs. PMID:26309782

  5. Factors Influencing the Prognosis of Octogenarians with Aortic Stenosis in the Advanced Aging Societies.

    PubMed

    Liang, Shuai; Yamaguchi, Kazuto; Yoshitomi, Hiroyuki; Ito, Saki; Nakashima, Ryuma; Sugamori, Takashi; Endo, Akihiro; Takahashi, Nobuyuki; Tanabe, Kazuaki

    2016-01-01

    Objective The recognition of clinical symptoms is critical to developing an effective therapeutic strategy for aortic valve stenosis (AS). Although AS is common, little is known about the factors influencing the natural history of AS patients who are 80 years of age older in advanced aging societies. We investigated the natural history and indications for valve procedures in AS patients of 80 years of age or older. Methods The medical records of 108 consecutive AS patients (moderate grade or higher) who are 80 years of age or older (mean age, 84.2±3.9 years; female, 65 patients) were reviewed to investigate their symptoms, the development of congestive heart failure, the incidence of referral for aortic valve replacement and death. The median duration of follow-up was 9 months (interquartile range, 2 to 25 months). Results The probability of remaining free of events (valve replacement and death) was 29±13% in all patients. There was no significant difference in the aortic valve area of the symptomatic and asymptomatic patients (0.85±0.28 cm(2) vs. 0.88±0.25 cm(2), p=0.59). The aortic valve (AV) velocity and AV area index were predictors of subsequent cardiac events (p<0.05). Conclusion The severity of AS was the only factor to affect the prognosis of AS patients who were 80 years old of age or older. It is necessary to frequently monitor the subjective symptoms of such patients and to objectively measure the AV area. PMID:27580533

  6. Diabetes mellitus--advances and challenges in human β-cell proliferation.

    PubMed

    Wang, Peng; Fiaschi-Taesch, Nathalie M; Vasavada, Rupangi C; Scott, Donald K; García-Ocaña, Adolfo; Stewart, Andrew F

    2015-04-01

    The treatment of diabetes mellitus represents one of the greatest medical challenges of our era. Diabetes results from a deficiency or functional impairment of insulin-producing β cells, alone or in combination with insulin resistance. It logically follows that the replacement or regeneration of β cells should reverse the progression of diabetes and, indeed, this seems to be the case in humans and rodents. This concept has prompted attempts in many laboratories to create new human β cells using stem-cell strategies to transdifferentiate or reprogramme non-β cells into β cells or to discover small molecules or other compounds that can induce proliferation of human β cells. This latter approach has shown promise, but has also proven particularly challenging to implement. In this Review, we discuss the physiology of normal human β-cell replication, the molecular mechanisms that regulate the cell cycle in human β cells, the upstream intracellular signalling pathways that connect them to cell surface receptors on β cells, the epigenetic mechanisms that control human β-cell proliferation and unbiased approaches for discovering novel molecules that can drive human β-cell proliferation. Finally, we discuss the potential and challenges of implementing strategies that replace or regenerate β cells.

  7. Alterations in Mouse Hypothalamic Adipokine Gene Expression and Leptin Signaling following Chronic Spinal Cord Injury and with Advanced Age

    PubMed Central

    Bigford, Gregory E.; Bracchi-Ricard, Valerie C.; Nash, Mark S.; Bethea, John R.

    2012-01-01

    Chronic spinal cord injury (SCI) results in an accelerated trajectory of several cardiovascular disease (CVD) risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF), resistin (Rstn), long-form leptin receptor (LepRb) and suppressor of cytokine-3 (SOCS3) gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER) stress and activation of the uncoupled protein response (UPR) as a biological hallmark of leptin resistance. We observe the activation of the ER stress/UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions. PMID:22815920

  8. The AGE-RAGE Axis and Its Relationship to Markers of Cardiovascular Disease in Newly Diagnosed Diabetic Patients

    PubMed Central

    Villegas-Rodríguez, Ma. Etzabel; Uribarri, Jaime; Solorio-Meza, Sergio E.; Fajardo-Araujo, Martha E.; Cai, Weijing; Torres-Graciano, Sofía; Rangel-Salazar, Rubén; Wrobel, Kazimierz; Garay-Sevilla, Ma. Eugenia

    2016-01-01

    Aim The purpose of the study was the simultaneous measurement of all the different components of the AGE-RAGE axis as well as several non-invasive markers of cardiovascular disease (CVD) in a cohort of newly diagnosed diabetic patients. Materials and Methods In 80 newly diagnosed diabetic patients we measured serum carboxymethyllysine (CML), soluble RAGE (sRAGE) and peripheral mononuclear (PMNC) RAGE and AGER1 mRNA together with ICAM-1, VCAM-1, and malondialdehyde (MDA). We also assessed cardiovascular function by measurement of flow-mediated vasodilation (FMD), intima-media thickness (IMT) and arterial stiffness. Univariant correlation analysis was used to determine correlation between the variables in the study and multiple regression analysis was used to examine the association between the AGE-RAGE axis components and FMD, IMT and arterial stiffness. Results Serum CML correlated positively with sRAGE, PMNC RAGE, HOMA-IR, ICAM-1, VCAM-1 and MDA, but inversely with PMNC AGER1. sRAGE and RAGE was positively correlated with AGER; IMT was positively correlated with HOMA-IR, ICAM-1, VCAM-1, MDA, and sRAGE and arterial stiffness had correlation with HOMA-IR, ICAM-1, VCAM-1, MDA, CML, sRAGE, AGER1 and RAGE. In multivariate analysis we found a significant relationship between CML with PMNC RAGE, HOMA-IR; sRAGE with VCAM-1 and MDA; PMNC RAGE with PMNC AGER1and CML; PMNC AGER1 with PMNC RAGE; FMD with sRAGE, CML and HbA1c; IMT with sRAGE, and arterial stiffness with sRAGE, sCML and AGER1 Conclusions We found significant and strong associations between the different components of the AGE-RAGE axis and also found significant association between AGE-RAGE axis markers, especially sRAGE with several noninvasive markers of cardiovascular disease risk. sRAGE, an easily measured parameter in blood, may potentially be used as a surrogate marker of AGEs-RAGE in patients with diabetes. PMID:27434539

  9. Ultrasonic Stimulation of Mouse Skin Reverses the Healing Delays in Diabetes and Aging by Activation of Rac1.

    PubMed

    Roper, James A; Williamson, Rosalind C; Bally, Blandine; Cowell, Christopher A M; Brooks, Rebecca; Stephens, Phil; Harrison, Andrew J; Bass, Mark D

    2015-11-01

    Chronic skin-healing defects are one of the leading challenges to lifelong well-being, affecting 2-5% of populations. Chronic wound formation is linked to age and diabetes and frequently leads to major limb amputation. Here we identify a strategy to reverse fibroblast senescence and improve healing rates. In healthy skin, fibronectin activates Rac1 in fibroblasts, causing migration into the wound bed, and driving wound contraction. We discover that mechanical stimulation of the skin with ultrasound can overturn healing defects by activating a calcium/CamKinaseII/Tiam1/Rac1 pathway that substitutes for fibronectin-dependent signaling and promotes fibroblast migration. Treatment of diabetic and aged mice recruits fibroblasts to the wound bed and reduces healing times by 30%, restoring healing rates to those observed in young, healthy animals. Ultrasound treatment is equally effective in rescuing the healing defects of animals lacking fibronectin receptors, and can be blocked by pharmacological inhibition of the CamKinaseII pathway. Finally, we discover that the migration defects of fibroblasts from human venous leg ulcer patients can be reversed by ultrasound, demonstrating that the approach is applicable to human chronic samples. By demonstrating that this alternative Rac1 pathway can substitute for that normally operating in the skin, we identify future opportunities for management of chronic wounds.

  10. IL12RB2 Gene Is Associated with the Age of Type 1 Diabetes Onset in Croatian Family Trios

    PubMed Central

    Pehlić, Marina; Vrkić, Dina; Škrabić, Veselin; Jerončić, Ana; Stipančić, Gordana; Urojić, Anita Špehar; Marjanac, Igor; Jakšić, Jasminka; Kačić, Zrinka; Boraska, Vesna; Zemunik, Tatijana

    2012-01-01

    Background Common complex diseases are influenced by both genetic and environmental factors. Many genetic factors overlap between various autoimmune diseases. The aim of the present study is to determine whether four genetic variants known to be risk variants for several autoimmune diseases could be associated with an increased susceptibility to type 1 diabetes mellitus. Methods and Findings We genotyped four genetic variants (rs2358817, rs1049550, rs6679356, rs9865818) within VTCN1, ANXA11, IL12RB2 and LPP genes respectively, in 265 T1DM family trios in Croatian population. We did not detect association of these polymorphisms with T1DM. However, quantitative transmission disequilibrium test (QTDT, orthogonal model) revealed a significant association between the age of onset of T1DM and IL12RB2 rs6679356 variant. An earlier onset of T1DM was associated with the rs6679356 minor dominant allele C (p = 0.005). The association remained significant even after the Bonferroni correction for multiple testing and permutation. Conclusions Variants originally associated with juvenile idiopathic arthritis (VTCN1 gene), sarcoidosis (ANXA11 gene), primary biliary cirrhosis (IL12RB2 gene) and celiac disease (LPP gene) were not associated with type 1 diabetes in our dataset. Nevertheless, association of IL12RB2 rs6679356 polymorphism with the age of T1DM onset suggests that this gene plays a role in defining the time of disease onset. PMID:23152861

  11. Immunohistochemical localization of GAP-43 in rat and human sympathetic nervous system--effects of aging and diabetes.

    PubMed

    Schmidt, R E; Spencer, S A; Coleman, B D; Roth, K A

    1991-06-28

    The neuronal 43 kDa growth associated peptide (GAP-43) is expressed in conditions of embryonic growth, axonal regeneration, and, to a limited degree, within the central nervous system as an indicator of synaptic plasticity. Although much is known about the expression of GAP-43 in cultured sympathetic neurons, information concerning the existence, immunolocalization and response of GAP-43 to experimental injury is not available for intact sympathetic ganglia in vivo. In this study we have characterized the in situ distribution and identity of GAP-43 in adult rat and human prevertebral and paravertebral sympathetic ganglia using immunohistochemical and biochemical methods. Antisera to GAP-43 intensely labeled intraganglionic presynaptic axons and synapses terminating on neurons of normal adult rat and human sympathetic ganglia in situ. There was minimal GAP-43 immunoreactivity of principal sympathetic neuron perikarya, proximal dendrites and initial axonal segments. The immunohistologic appearance of GAP-43 was unchanged in the ganglia of aged and diabetic rats and elderly humans, conditions in which presynaptic terminal axons and synapses show evidence of chronic degeneration, regeneration and neuroaxonal dystrophy, an unusual ultrastructural alteration which may represent disordered synaptic plasticity. Radioimmunoassay of ganglionic GAP-43 is comparable in young adult, aged and diabetic rat prevertebral or paravertebral sympathetic ganglia. Double immunolocalization of NPY (which labeled markedly swollen dystrophic axons) and GAP-43 in human sympathetic ganglia using a sequential immunogold-silver/fluorescence technique demonstrated that typical dystrophic axons contain little GAP-43.

  12. Ultrasonic stimulation of mouse skin reverses the healing delays in diabetes and aging by activation of Rac1

    PubMed Central

    Roper, James A; Williamson, Rosalind C; Bally, Blandine; Cowell, Christopher AM; Brooks, Rebecca; Stephens, Phil; Harrison, Andrew J; Bass, Mark D

    2015-01-01

    Chronic skin healing defects are one of the leading challenges to lifelong wellbeing, affecting 2-5% of populations. Chronic wound formation is linked to age and diabetes and frequently leads to major limb amputation. Here we identify a strategy to reverse fibroblast senescence and improve healing rates. In healthy skin, fibronectin activates Rac1 in fibroblasts, causing migration into the wound bed and driving wound contraction. We discover that mechanical stimulation of skin with ultrasound can overturn healing defects by activating a calcium/CamKinaseII/Tiam1/Rac1 pathway that substitutes for fibronectin-dependent signaling and promotes fibroblast migration. Treatment of diabetic and aged mice recruits fibroblasts to the wound bed and reduces healing times by 30%, restoring healing rates to those observed in young, healthy animals. Ultrasound treatment is equally effective in rescuing the healing defects of animals lacking fibronectin receptors, and can be blocked by pharmacological inhibition of the CamKinaseII pathway. Finally, we discover that the migration defects of fibroblasts from human venous leg ulcer patients can be reversed by ultrasound, demonstrating that the approach is applicable to human chronic samples. By demonstrating that this alternative Rac1 pathway can substitute for that normally operating in skin, we identify future opportunities for management of chronic wounds. PMID:26079528

  13. Advantage of a low glycemic index and low phosphate diet on diabetic nephropathy and aging-related diseases.

    PubMed

    Taketani, Yutaka; Shuto, Emi; Arai, Hidekazu; Nishida, Yuka; Tanaka, Rieko; Uebanso, Takashi; Yamamoto, Hironori; Yamanaka-Okumura, Hisami; Takeda, Eiji

    2007-08-01

    Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in Japan and other Westernized countries. Over 50% of the ESRD patients die from cardiovascular events. Cardiovascular disease (CVD) in ESRD patients with diabetes mellitus (DM) are implicated in the endothelial dysfunction caused by hyperglycemia, hyperlipidemia, and hypertension, and in the vascular calcification of intimal and medial arterial blood vessels caused by hyperphosphatemia. Therefore, dietary control of hyperglycemia and hyperphosphatemia should play an important role in the management of ESRD patients with DM. Furthermore, recent findings suggest that high concentrations of serum phosphate, even if within the normal range, may be a risk factor for CVD and mortality. An in vivo study using klotho knockout mice and fibroblast growth factor 23 (FGF-23) knockout mice has revealed that correction of hyperphosphatemia and hypervitaminosis D could ameliorate the premature aging-like phenotype. A low glycemic index and low phosphate diet may provide an advantage in the prevention of aging-related diseases in healthy individuals as well as in those with chronic kidney disease.

  14. Accurate assessment of early gestational age in normal and diabetic women by serum human placental lactogen concentration.

    PubMed

    Whittaker, P G; Aspillaga, M O; Lind, T

    1983-08-01

    Serum human placental lactogen (hPL) and human chorionic gonadotropin (hCG) were assayed and fetal crown-rump length (CRL) was determined by sonar in three groups of pregnant women--35 with uncomplicated pregnancies, 13 with insulin-dependent diabetes mellitus, and 21 who represented a general pregnancy population. Each patient had a regular cycle and recorded last menstrual period, ovulated spontaneously, and was delivered of a single live baby. Serum hPL concentrations within the range 0.01-0.80 microU/ml in patients in the first group gave estimates of gestation with an SD of 6.3 days which was the same as the SD derived from CRL measurements. When the hPL regression equation was applied to the diabetic mothers the difference between the gestational age estimated from hPL and that estimated from LMP had a mean value of - 0.9 days with an SD of 6.2 days; this difference was not significantly different from zero. The third group of patients had a mean difference between hPL and LMP derived gestational age of 0.7 days (+/- 6.7 SD). Serum hPL offers a method of estimating gestation sufficiently precise to be used as a practical alternative to sonar measurements of CRL.

  15. Polyphenol isolated from Corni Fructus, 7-O-galloyl-D-sedoheptulose, modulates advanced glycation endproduct-related pathway in type 2 diabetic db/db mice.

    PubMed

    Park, Chan Hum; Noh, Jeong Sook; Tanaka, Takashi; Roh, Seong-Soo; Lee, Jang Cheon; Yokozawa, Takako

    2015-06-01

    7-O-Galloyl-D-sedoheptulose (GS) is the bioactive polyphenol isolated from the low-molecular-weight fraction of Corni Fructus (Cornus officinalis Sieb. et Zucc.). The present study was conducted to examine whether GS has an ameliorative effect on the liver of type 2 diabetic db/db mice. GS (20 or 100 mg/kg body weight/day, per os) was administered every day for 6 weeks to db/db mice, and its effect was compared with vehicle-treated db/db and m/m mice. The administration of GS decreased the elevated serum glucose, leptin, insulin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), resistin, and hepatic functional parameters, and reduced the increased fluorescent advanced glycation endproducts (AGEs) and reactive oxygen species in the liver. The db/db mice exhibited the up-regulation of receptor for AGEs (RAGE) and AGE-related proteins; however, GS treatment significantly reduced those expressions. Moreover, the augmented expressions of oxidative stress- and inflammation-related proteins, phospho-extracellular-signal regulated kinase 1/2, phospho-c-Jun N-terminal kinase, nuclear factor-kappa B, activator protein-1, monocyte chemotactic protein-1, intracellular adhesion molecule-1, TNF-α, and IL-6, were down-regulated by GS administration. Hematoxylin-eosin staining showed that the increased hepatocellular damage in the liver of db/db mice improved with GS administration. The present results support the evidence for GS ameliorating hepatic damage through the RAGE-mediated inflammation pathway.

  16. Cannon ball appearance on radiology in a middle-aged diabetic female

    PubMed Central

    Kshatriya, Ravish; Patel, Viral; Chaudhari, Sanjay; Patel, Purvesh; Prajapati, Dhaval; Khara, Nimit; Paliwal, Rajiv; Patel, Sateesh

    2016-01-01

    Pulmonary tuberculosis is commonly presented as cavitary lesion and infiltrations. It commonly involves upper lobe. Lower lobe involvement is less common. Various atypical presentations of tuberculosis on radiology are reported like mass, solitary nodule, multi lober involvement including lower lobes. Atypical presentations are more commo in patients with immunocompromised conditions like Diabetes Mellitus, anemia, renal failure, liver diseases, HIV infection, malignancy, patients on immunosuppressive therapy. Cannon ball presentation of pulmonary tuberculosis is extremely rare and not so common. Common causes of cannon ball presentation in lung are metastasis, fungal infections, Wegener's grannulomatosis, sarcoidosis, etc. We report here a case of middle year female with diabetes mellitus presented with atypical symptoms with cannon ball appearance on radiology and found to be of tuberculosis in origin. Thus any patients with immunocompromised condition can present with atypical manifestation of tuberculosis either clinically or radiologicaly in high endemic countries for tuberculosis. PMID:27625459

  17. Cannon ball appearance on radiology in a middle-aged diabetic female

    PubMed Central

    Kshatriya, Ravish; Patel, Viral; Chaudhari, Sanjay; Patel, Purvesh; Prajapati, Dhaval; Khara, Nimit; Paliwal, Rajiv; Patel, Sateesh

    2016-01-01

    Pulmonary tuberculosis is commonly presented as cavitary lesion and infiltrations. It commonly involves upper lobe. Lower lobe involvement is less common. Various atypical presentations of tuberculosis on radiology are reported like mass, solitary nodule, multi lober involvement including lower lobes. Atypical presentations are more commo in patients with immunocompromised conditions like Diabetes Mellitus, anemia, renal failure, liver diseases, HIV infection, malignancy, patients on immunosuppressive therapy. Cannon ball presentation of pulmonary tuberculosis is extremely rare and not so common. Common causes of cannon ball presentation in lung are metastasis, fungal infections, Wegener's grannulomatosis, sarcoidosis, etc. We report here a case of middle year female with diabetes mellitus presented with atypical symptoms with cannon ball appearance on radiology and found to be of tuberculosis in origin. Thus any patients with immunocompromised condition can present with atypical manifestation of tuberculosis either clinically or radiologicaly in high endemic countries for tuberculosis.

  18. Cannon ball appearance on radiology in a middle-aged diabetic female.

    PubMed

    Kshatriya, Ravish; Patel, Viral; Chaudhari, Sanjay; Patel, Purvesh; Prajapati, Dhaval; Khara, Nimit; Paliwal, Rajiv; Patel, Sateesh

    2016-01-01

    Pulmonary tuberculosis is commonly presented as cavitary lesion and infiltrations. It commonly involves upper lobe. Lower lobe involvement is less common. Various atypical presentations of tuberculosis on radiology are reported like mass, solitary nodule, multi lober involvement including lower lobes. Atypical presentations are more commo in patients with immunocompromised conditions like Diabetes Mellitus, anemia, renal failure, liver diseases, HIV infection, malignancy, patients on immunosuppressive therapy. Cannon ball presentation of pulmonary tuberculosis is extremely rare and not so common. Common causes of cannon ball presentation in lung are metastasis, fungal infections, Wegener's grannulomatosis, sarcoidosis, etc. We report here a case of middle year female with diabetes mellitus presented with atypical symptoms with cannon ball appearance on radiology and found to be of tuberculosis in origin. Thus any patients with immunocompromised condition can present with atypical manifestation of tuberculosis either clinically or radiologicaly in high endemic countries for tuberculosis. PMID:27625459

  19. Paediatric diabetes.

    PubMed

    Kalra, Sanjay

    2013-09-01

    Diabetes does not spare any section of society, and its prevalence in the paediatric and adolescent age group is rising. This review highlights the etiological and clinical features of childhood diabetes, including secular changes in epidemiology. It discusses the aspects of non pharmacological and pharmacological therapy which are unique to the paediatric age group, and explores current use of novel therapeutic modalities. The article calls for modulation of the psychological environment of the child with diabetes, to help improve his or her quality of life, and sensitizes physicians to take proactive, affirmative action to address the special needs of children with type1 diabetes. PMID:24601207

  20. Role of Pro-Inflammatory Cytokines and Biochemical Markers in the Pathogenesis of Type 1 Diabetes: Correlation with Age and Glycemic Condition in Diabetic Human Subjects

    PubMed Central

    Zubair, Swaleha; Ajmal, Mohd; Siddiqui, Sheelu Shafiq; Moin, Shagufta; Owais, Mohammad

    2016-01-01

    Background Type 1 diabetes mellitus is a chronic inflammatory disease involving insulin producing β-cells destroyed by the conjoined action of auto reactive T-cells, inflammatory cytokines and monocytic cells. The aim of this study was to elucidate the status of pro-inflammatory cytokines and biochemical markers and possible correlation of these factors towards outcome of the disease. Methods The study was carried out on 29 T1D subjects and 20 healthy subjects. Plasma levels of oxidative stress markers, enzymatic and non-enzymatic antioxidants were estimated employing biochemical assays. The levels of pro-inflammatory cytokines such as by IL-1β & IL-17 in the serum were determined by ELISA, while the expression of TNF-α, IL-23 & IFN-γ was ascertained by qRT-PCR. Results The onset of T1D disease was accompanied with elevation in levels of Plasma malondialdehyde, protein carbonyl content and nitric oxide while plasma vitamin C, reduced glutathione and erythrocyte sulfhydryl groups were found to be significantly decreased in T1D patients as compared to healthy control subjects. Activity of antioxidant enzymes, superoxide dismutase, catalase, glutathione reductase and glutathione-s-transferase showed a significant suppression in the erythrocytes of T1D patients as compared to healthy subjects. Nevertheless, the levels of pro-inflammatory cytokines IL-1β and IL-17A were significantly augmented (***p≤.001) on one hand, while expression of T cell based cytokines IFN-γ, TNF-α and IL-23 was also up-regulated (*p≤.05) as compared to healthy human subjects. Conclusion The level of pro-inflammatory cytokines and specific biochemical markers in the serum of the patient can be exploited as potential markers for type 1 diabetes pathogenesis. The study suggests that level of inflammatory markers is up-regulated in T1D patients in an age dependent manner. PMID:27575603

  1. Pathophysiology of Diabetic Retinopathy

    PubMed Central

    Tarr, Joanna M.; Kaul, Kirti; Chopra, Mohit; Kohner, Eva M.; Chibber, Rakesh

    2013-01-01

    Diabetes is now regarded as an epidemic, with the population of patients expected to rise to 380 million by 2025. Tragically, this will lead to approximately 4 million people around the world losing their sight from diabetic retinopathy, the leading cause of blindness in patients aged 20 to 74 years. The risk of development and progression of diabetic retinopathy is closely associated with the type and duration of diabetes, blood glucose, blood pressure, and possibly lipids. Although landmark cross-sectional studies have confirmed the strong relationship between chronic hyperglycaemia and the development and progression of diabetic retinopathy, the underlying mechanism of how hyperglycaemia causes retinal microvascular damage remains unclear. Continued research worldwide has focussed on understanding the pathogenic mechanisms with the ultimate goal to prevent DR. The aim of this paper is to introduce the multiple interconnecting biochemical pathways that have been proposed and tested as key contributors in the development of DR, namely, increased polyol pathway, activation of protein kinase C (PKC), increased expression of growth factors such as vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), haemodynamic changes, accelerated formation of advanced glycation endproducts (AGEs), oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and subclinical inflammation and capillary occlusion. New pharmacological therapies based on some of these underlying pathogenic mechanisms are also discussed. PMID:24563789

  2. HbA1c Alone Is a Poor Indicator of Cardiometabolic Risk in Middle-Aged Subjects with Pre-Diabetes but Is Suitable for Type 2 Diabetes Diagnosis: A Cross-Sectional Study

    PubMed Central

    Millar, Seán R.; Perry, Ivan J.; Phillips, Catherine M.

    2015-01-01

    Objectives Glycated haemoglobin A1c (HbA1c) measurement is recommended as an alternative to fasting plasma glucose (FPG) for the diagnosis of pre-diabetes and type 2 diabetes. However, evidence suggests discordance between HbA1c and FPG. In this study we examine a range of metabolic risk features, pro-inflammatory cytokines, acute-phase response proteins, coagulation factors and white blood cell counts to determine which assay more accurately identifies individuals at increased cardiometabolic risk. Materials and Methods This was a cross-sectional study involving a random sample of 2,047 men and women aged 46-73 years. Binary and multinomial logistic regression were employed to examine risk feature associations with pre-diabetes [either HbA1c levels 5.7-6.4% (39-46 mmol/mol) or impaired FPG levels 5.6-6.9 mmol/l] and type 2 diabetes [either HbA1c levels >6.5% (>48 mmol/mol) or FPG levels >7.0 mmol/l]. Receiver operating characteristic curve analysis was used to evaluate the ability of HbA1c to discriminate pre-diabetes and diabetes defined by FPG. Results Stronger associations with diabetes-related phenotypes were observed in pre-diabetic subjects diagnosed by FPG compared to those detected by HbA1c. Individuals with type 2 diabetes exhibited cardiometabolic profiles that were broadly similar according to diagnosis by either assay. Pre-diabetic participants classified by both assays displayed a more pro-inflammatory, pro-atherogenic, hypertensive and insulin resistant profile. Odds ratios of having three or more metabolic syndrome features were also noticeably increased (OR: 4.0, 95% CI: 2.8-5.8) when compared to subjects diagnosed by either HbA1c (OR: 1.4, 95% CI: 1.2-1.8) or FPG (OR: 3.0, 95% CI: 1.7-5.1) separately. Conclusions In middle-aged Caucasian-Europeans, HbA1c alone is a poor indicator of cardiometabolic risk but is suitable for diagnosing diabetes. Combined use of HbA1c and FPG may be of additional benefit for detecting individuals at highest odds of

  3. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson’s Disease

    PubMed Central

    Claassen, Daniel O.; Dobolyi, David G.; Isaacs, David A.; Roman, Olivia C.; Herb, Joshua; Wylie, Scott A.; Neimat, Joseph S.; Donahue, Manus J.; Hedera, Peter; Zald, David H.; Landman, Bennett A.; Bowman, Aaron B.; Dawant, Benoit M.; Rane, Swati

    2016-01-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson’s disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson’s Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2nd, or 3rd order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning. PMID:27330836

  4. Recent Demographic Developments in France: Relatively Low Mortality at Advanced Ages

    PubMed Central

    Prioux, France; Barbieri, Magali

    2013-01-01

    France had 65.3 million inhabitants as of 1 January 2012, including 1.9 million in the overseas départements. The population is slightly younger than that of the European Union as a whole. Population growth continues at the same rate, mainly through natural increase. There are now more African than European immigrants living in France. Fertility was practically stable in 2011 (2.01 children per woman), but the lifetime fertility of the 1971–1972 cohorts reached a historic low in metropolitan France (1.99 children per woman), nevertheless remaining among the highest in Europe. Abortion levels remained stable and rates among young people are no longer increasing. The marriage rate is falling and the divorce rate has stabilized (46.2 divorces per 100 marriages in 2011). The risk of divorce decreases with age, but has greatly increased among the under-70s over the last decade. Life expectancy at birth (78.4 years for men, 85.0 for women) has continued to increase at the same rate, mainly thanks to progress at advanced ages. Among European countries, France has the lowest mortality in the over-65 age group, but it ranks less well for premature mortality. PMID:24285939

  5. Advances in the treatment of type 2 diabetes: impact of dulaglutide.

    PubMed

    Thompson, Angela M; Trujillo, Jennifer M

    2016-01-01

    The purpose of this review is to provide a review of current data of the most recently approved glucagon-like peptide (GLP)-1-receptor agonist, dulaglutide, in the treatment of type 2 diabetes. To complete this, a PubMed search was performed to identify manuscripts published from 1947 to July 2015. The search terms "Trulicity", "dulaglutide", and "LY2189265" were utilized, and publications were included if they evaluated the pharmacology, pharmacokinetics, efficacy, safety, or patient-reported outcomes of dulaglutide. Dulaglutide is a GLP-1 receptor agonist that mimics endogenous GLP-1, the hormone produced in response to food intake. Modifications have been made to the molecule to delay breakdown and allow for once-weekly dosing. Dulaglutide has been studied as monotherapy and in combination with several agents, including metformin, glimepiride, pioglitazone, and insulin lispro. Dulaglutide has demonstrated superior efficacy compared to placebo, metformin, insulin glargine, sitagliptin, and twice-daily exenatide. It was found to be noninferior to liraglutide. The most common adverse effects in clinical studies were gastrointestinal-related adverse events, and patient satisfaction was high with the use of dulaglutide. Dulaglutide is an appealing option for the treatment of type 2 diabetes, based on its once-weekly dosing, A1c lowering comparable to liraglutide, weight reduction comparable to exenatide, and a similar adverse-effect profile to other GLP-1 receptor agonists. PMID:27217788

  6. Advances in the treatment of type 2 diabetes: impact of dulaglutide

    PubMed Central

    Thompson, Angela M; Trujillo, Jennifer M

    2016-01-01

    The purpose of this review is to provide a review of current data of the most recently approved glucagon-like peptide (GLP)-1-receptor agonist, dulaglutide, in the treatment of type 2 diabetes. To complete this, a PubMed search was performed to identify manuscripts published from 1947 to July 2015. The search terms “Trulicity”, “dulaglutide”, and “LY2189265” were utilized, and publications were included if they evaluated the pharmacology, pharmacokinetics, efficacy, safety, or patient-reported outcomes of dulaglutide. Dulaglutide is a GLP-1 receptor agonist that mimics endogenous GLP-1, the hormone produced in response to food intake. Modifications have been made to the molecule to delay breakdown and allow for once-weekly dosing. Dulaglutide has been studied as monotherapy and in combination with several agents, including metformin, glimepiride, pioglitazone, and insulin lispro. Dulaglutide has demonstrated superior efficacy compared to placebo, metformin, insulin glargine, sitagliptin, and twice-daily exenatide. It was found to be noninferior to liraglutide. The most common adverse effects in clinical studies were gastrointestinal-related adverse events, and patient satisfaction was high with the use of dulaglutide. Dulaglutide is an appealing option for the treatment of type 2 diabetes, based on its once-weekly dosing, A1c lowering comparable to liraglutide, weight reduction comparable to exenatide, and a similar adverse-effect profile to other GLP-1 receptor agonists. PMID:27217788

  7. Cable aging and condition monitoring of radiation resistant nano-dielectrics in advanced reactor applications

    SciTech Connect

    Duckworth, Robert C; Aytug, Tolga; Paranthaman, Mariappan Parans; Kidder, Michelle; Polyzos, Georgios; Leonard, Keith J

    2015-01-01

    Cross-linked polyethylene (XLPE) nanocomposites have been developed in an effort to improve cable insulation lifetime to serve in both instrument cables and auxiliary power systems in advanced reactor applications as well as to provide an alternative for new or retro-fit cable insulation installations. Nano-dielectrics composed of different weight percentages of MgO & SiO2 have been subjected to radiation at accumulated doses approaching 20 MRad and thermal aging temperatures exceeding 100 C. Depending on the composition, the performance of the nanodielectric insulation was influenced, both positively and negatively, when quantified with respect to its electrical and mechanical properties. For virgin unradiated or thermally aged samples, XLPE nanocomposites with 1wt.% SiO2 showed improvement in breakdown strength and reduction in its dissipation factor when compared to pure undoped XLPE, while XLPE 3wt.% SiO2 resulted in lower breakdown strength. When aged in air at 120 C, retention of electrical breakdown strength and dissipation factor was observed for XLPE 3wt.% MgO nanocomposites. Irrespective of the nanoparticle species, XLPE nanocomposites that were gamma irradiated up to the accumulated dose of 18 MRad showed a significant drop in breakdown strength especially for particle concentrations greater than 3 wt.%. Additional attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy measurements suggest changes in the structure of the XLPE SiO2 nanocomposites associated with the interaction of silicon and oxygen. Discussion on the relevance of property changes with respect to cable aging and condition monitoring is presented.

  8. Clinical profile of patients with advanced age and inflammatoric dilated cardiomyopathy on endomyocardial biopsy

    PubMed Central

    Ohlow, Marc-Alexander; Chen, Ting-Hui; Schmidt, Andreas; Saenger, Joerg; Lauer, Bernward

    2015-01-01

    Background Endomyocardial biopsy (EMB) is an important tool when patients with inflammatoric cardiomyopathy (DCMi) are evaluated. We aimed to assess the clinical profile of elderly patients with DCMi on EMB. Methods Retrospective study of all consecutive patients hospitalized from January 2007 to December 2011 with clinical suspicion of DCMi undergoing EMB. Patients with evidence of DCMi on EMB (Group 1 ≥ 70 years, n = 85; Group 3 < 70 years; n = 418) were compared to patients of the same age group without evidence of DCMi on EMB (Group 2 ≥ 70 years, n = 45; Group 4 < 70 years; n = 147). Results Among 24,275 patients treated at our institution during the study period, 695 had clinical suspicion of DCMi and underwent EMB; 503 (2.1%) patients had DCMi on EMB. There were more male patients in Group 1, mean age was 74 ± 2.8 years, mean ejection fraction was 38% ± 14%. On presentation, signs of hemodynamic compromise (NYHA functional class III/IV, low cardiac output/index, and low cardiac power index) were more frequent in Group 1. EMB revealed viral genome in 78% of the patients, parvovirus B19 (PVB) was frequently encountered in both age groups (Group 1: 69.4% vs. Group 2: 59.6%); detection of more than one viral genome was more frequent in Group 1 (21.2% vs. 11.2%; P = 0.02) whereas the extent of immune response was significantly lower in individuals with advanced age. Conclusions In patients ≥ 70 years with DCMi on EMB signs of hemodynamic compromise, detection of multiple viral genomes together with an overall lower extent of immune response were more frequently observed. PMID:26788036

  9. Effects of Sevelamer Carbonate on Advanced Glycation End Products and Antioxidant/Pro-Oxidant Status in Patients with Diabetic Kidney Disease

    PubMed Central

    Yubero-Serrano, Elena M.; Woodward, Mark; Poretsky, Leonid; Vlassara, Helen

    2015-01-01

    Background and objectives The primary goals were to re-examine whether sevelamer carbonate (SC) reduces advanced glycation end products (AGEs) (methylglyoxal and carboxymethyllysine [CML]), increases antioxidant defenses, reduces pro-oxidants, and improves hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Secondary goals examined albuminuria, age, race, sex, and metformin prescription. Design, setting, participants, & measurements This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM (HbA1c >6.5%) and stages 2–4 DKD (urinary albumin/creatinine ratio ≥200 mg/g) treated with SC (1600 mg) or calcium carbonate (1200 mg), three times a day, without changing medications or diet. Statistical analyses used linear mixed models adjusted for randomization levels. Preselected subgroup analyses of sex, race, age, and metformin were conducted. Results SC lowered serum methylglyoxal (95% confidence interval [CI], −0.72 to −0.29; P<0.001), serum CML (95% CI, −5.08 to −1.35; P≤0.001), and intracellular CML (95% CI, −1.63 to −0.28; P=0.01). SC increased anti-inflammatory defenses, including nuclear factor like-2 (95% CI, 0.58 to 1.29; P=0.001), AGE receptor 1 (95% CI, 0.23 to 0.96; P=0.001), NAD-dependent deacetylase sirtuin-1 (95% CI, 0.20 to 0.86; P=0.002), and estrogen receptor α (95% CI, 1.38 to 2.73; P ≤0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95% CI, −1.56 to −0.72; P≤0.001) and the receptor for AGEs (95% CI, −0.58 to 1.53; P≤0.001). There were no differences in HbA1c, GFR, or albuminuria in the overall group. Subanalyses showed that SC lowered HbA1c in women (95% CI, −1.71 to −0.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged <65 years (95% CI, −1.15 to −0.07; P=0.03, interaction P=0.02) and non-Caucasians (95% CI, −1.11 to −0.22; P=0.003, interaction P≤0.001), whereas

  10. Effect of age and Blood Pressure on Surrogate Markers of Atherosclerosis in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Kulkarni, Namrata Bindurao; Ganu, Meghana Ulhas; Godbole, Sanjay Ganesh

    2014-01-01

    Background: Increased arterial stiffness may be an important path- way linking diabetes mellitus to increased cardiovascular risk. Aim: The study was conducted to assess the surrogate markers of arterial stiffness in patients with Type 2 diabetes mellitus (T2DM), and compare with age-matched hypertensive and healthy controls. Also the effect of age and blood pressure on these markers was evaluated. Settings and Design: This cross-sectional study was carried out at a tertiary care hospital in West India. Methods: After a detailed medical history and anthropometric evaluation, all the participants were subjected to measurements of Arterial Stiffness Index (ASI), Pulse Wave Velocity (PWV), and Augmentation Index (AIx) using a non-invasive oscillometric method. The four study groups consisted of patients with T2DM (>5 years) along with hypertension, newly diagnosed patients with T2DM (<2years) without hypertension, hypertensive controls, and healthy controls. Results: PWV, ASI, AIx were elevated in patients with T2DM compared to healthy controls (p<0.05). Patients with T2DM above 60 years had higher carotid-femoral PWV, ASI and AIx than those below 60 years (p<0.05). ASI and AIx were significantly increased in patients with T2DM with hypertension having systolic BP > 140 mmHg compared to those with systolic BP < 140 mmHg. A very strong correlation between PWV and AIx in patients with T2DM and hypertensive controls was observed. Conclusion: This study reveals that markers of arterial stiffness (PWV, ASI, AIx) were increased significantly in patients with T2DM compared to healthy controls. Age and systolic blood pressure had significant influence on these markers. Thus, oscillometric markers have potential utility in identifying subclinical atherosclerosis in patients with T2DM. PMID:25120969

  11. Intensive Weight Loss Intervention in Individuals Ages 65 Years or Older: Results from the Look AHEAD Type 2 Diabetes Trial

    PubMed Central

    Espeland, Mark A.; Rejeski, W. Jack; West, Delia S.; Bray, George A.; Clark, Jeanne M.; Peters, Anne L.; Chen, Haiying; Johnson, Karen C.; Horton, Edward S.; Hazuda, Helen P.

    2013-01-01

    OBJECTIVES To compare the relative effects of four years of intensive lifestyle intervention on weight, fitness, and cardiovascular disease risk factors among older versus younger individuals DESIGN A randomized controlled clinical trial SETTING 16 US clinical sites PARTICIPANTS Individuals with type 2 diabetes: 1,053 aged 65–76 years and 4,092 aged 45–64 years INTERVENTIONS An intensive behavioral intervention designed to promote and maintain weight loss through caloric restriction and increased physical activity compared to a condition of diabetes support and education. MEASUREMENTS Standardized assessments of weight, fitness (based on graded exercise testing), and cardiovascular disease risk factors RESULTS Across four years, older individuals had greater intervention-related mean weight losses than younger participants, 6.2% versus 5.1% (interaction p=0.006) and comparable relative mean increases in fitness, 0.56 versus 0.53 metabolic equivalents (interaction p=0.72). These benefits were seen consistently across subgroups of older adults formed by many demographic and health factors. Among a panel of age-related health conditions, only self-reported worsening vision was associated with poorer intervention-related weight loss in older individuals. The intensive lifestyle intervention produced mean increases in high density lipoprotein cholesterol (2.03 mg/dl; p<0.001) and decreases in glycated hemoglobin (0.21%; p<0.001) and waist girth (3.52 cc; p<0.001) across 4 years that were at least as large in older compared to younger individuals. CONCLUSION Intensive lifestyle intervention targeting weight loss and increased physical activity is effective in overweight and obese older individuals to produce sustained weight loss and improvements in fitness and cardiovascular risk factors. PMID:23668423

  12. The relation of chronic cardiovascular diseases and diabetes mellitus to perceived health, and the moderating effects of sex and age.

    PubMed

    Ho, Sai Yin; Mak, Kwok Kei; Thomas, G Neil; Schooling, Mary; Fielding, Richard; Janus, Edward D; Lam, Tai Hing

    2007-10-01

    This study investigates the relation of five chronic cardiovascular diseases and diabetes mellitus (DM) to perceived health, and the moderating effects of sex and age. In a community-based cross-sectional telephone survey in Hong Kong, 7730 Chinese aged 25-74 were interviewed in 1994-1996. The odds ratio for poor perceived health associated with each condition was calculated adjusting for age, sex and education. Subjects free from the six conditions were treated as the comparison group. Hypertension, angina, DM, coronary heart disease (CHD) and stroke were significantly associated with poor perceived health. The odds ratio of poor perceived health was significantly greater in men than in women for having more than one condition among DM, CHD and stroke (p=0.02), and insignificantly greater for stroke, CHD and angina. The odds ratios were significantly greater in the young (25-39) versus the old (60-74) for DM (p=0.008) in men and women combined, and for having either DM, CHD or stroke in men (p=0.02). These findings suggest that the relation of DM, CHD and stroke with poor perceived health tends to be stronger in men and younger adults. These findings have implications for health care workers and home carers who need to appreciate that the same condition may have a different perceived impact on persons of different sex and age, and be sensitive to their varying needs.

  13. Marfanoid habitus, inguinal hernia, advanced bone age, and distinctive facial features: a new collagenopathy?

    PubMed

    Mégarbané, André; Hanna, Nadine; Chouery, Eliane; Jalkh, Nadine; Mehawej, Cybel; Boileau, Catherine

    2012-05-01

    We report on two sibs, a girl, and a boy, with tall stature, long, and triangular faces, prominent foreheads with high frontal hairlines, telecanthus, downward slanting of the palpebral fissures, ptosis of the eyelids, everted lower eyelids, large ears, long noses, full, and everted vermilions, highly arched and narrow palates, tooth crowding, thin and long uvulae, coloboma of the alae, hyperextensible joints, long digits, positive thumb signs, flat feet, slightly diminished muscle strength, myopia, astigmatia, inguinal hernia, and vesical diverticula. Total body X-rays showed the presence of advanced bone age in both sibs and bilateral hallux valgus in the girl. Array-CGH did not reveal any pathological CNV. Molecular analysis of FBN1, FBN2, TGFBR1, TGFBR2, and CHST14 gene was normal, and SNP linkage analysis excluded more candidate genes. Differential diagnoses and the possibility that we might be reporting on a hitherto unreported syndrome are discussed.

  14. Cadmium, type 2 diabetes, and kidney damage in a cohort of middle-aged women

    SciTech Connect

    Barregard, Lars; Bergström, Göran; Fagerberg, Björn

    2014-11-15

    Background: It has been proposed that diabetic patients are more sensitive to the nephrotoxicity of cadmium (Cd) compared to non-diabetics, but few studies have examined this in humans, and results are inconsistent. Aim: To test the hypothesis that women with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) have higher risk of kidney damage from cadmium compared to women with normal glucose tolerance (NGT). Methods: All 64-year-old women in Gothenburg, Sweden, were invited to a screening examination including repeated oral glucose tolerance tests. Random samples of women with DM, IGT, and NGT were recruited for further clinical examinations. Serum creatinine was measured and used to calculate estimated glomerular filtration rate (eGFR). Albumin (Alb) and retinol-binding protein (RBP) were analyzed in a 12 h urine sample. Cadmium in blood (B-Cd) and urine (U-Cd) was determined using inductively coupled plasma mass spectrometry. Associations between markers of kidney function (eGFR, Alb, and RBP) and quartiles of B-Cd and U-Cd were evaluated in models, including also blood pressure and smoking habits. Results: The mean B-Cd (n=590) was 0.53 µg/L (median 0.34 µg/L). In multivariable models, a significant interaction was seen between high B-Cd (upper quartile, >0.56 µg/L) and DM (point estimate +0.40 mg Alb/12 h, P=0.04). In stratified analyzes, the effect of high B-Cd on Alb excretion was significant in women with DM (53% higher Alb/12 h, P=0.03), but not in women with IGT or NGT. Models with urinary albumin adjusted for creatinine showed similar results. In women with DM, the multivariable odds ratio (OR) for microalbuminuria (>15 mg/12 h) was increased in the highest quartile of B-Cd vs. B-Cd quartiles 1–3 in women with DM (OR 4.2, 95% confidence interval 1.1–12). No such effect was found in women with IGT or NGT. There were no associations between B-Cd and eGFR or excretion of RBP, and no differences between women with DM, IGT, or NGT

  15. Increased Expression of Tissue Factor and Receptor for Advanced Glycation End Products in Peripheral Blood Mononuclear Cells of Patients With Type 2 Diabetes Mellitus with Vascular Complications

    PubMed Central

    Buchs, A. E.; Kornberg, A.; Zahavi, M.; Aharoni, D.; Zarfati, C.; Rapoport, M. J.

    2004-01-01

    The aim of the study was to determine the correlation between the expression of tissue factor (TF) and the receptor for advanced glycation end products (RAGEs) and vascular complications in patients with longstanding uncontrolled type 2 diabetes (T2D). TF and RAGE mRNAs as well as TF antigen and activity were investigated in 21 T2D patients with and without vascular complications. mRNA expression was assessed by reverse transcriptase–polymerase chain reaction (RT-PCR) in nonstimulated and advanced glycation end product (AGE) albumin–stimulated peripheral blood mononuclear cells (PBMCs). TF antigen expression was determined by enzyme-linked immunosorbent assay (ELISA) and TF activity by a modified prothrombin time assay. Basal RAGE mRNA expression was 0.2 ± 0.06 in patients with complications and 0.05 ± 0.06 patients without complications (P = .004). Stimulation did not cause any further increase in either group. TF mRNA was 0.58 ± 0.29 in patients with complications and 0.21 ± 0.18 in patients without complications (P = .003). Stimulation resulted in a nonsignificant increase in both groups. Basal TF activity (U/106 PBMCs) was 18.4 ± 13.2 in patients with complications and 6.96 ± 5.2 in patients without complications (P = .003). It increased 3-fold in both groups after stimulation (P = .001). TF antigen (pg/106 PBMCs) was 33.7 ± 28.6 in patients with complications, 10.4 ± 7.8 in patients without complications (P = .02). Stimulation tripled TF antigen in both groups of patients (P = .001). The RAGE/TF axis is up-regulated inT2Dpatients with vascular complications as compared to patients without complications. This suggests a role for this axis in the pathogenesis of vascular complications in T2D. PMID:15203887

  16. Centenarians as super-controls to assess the biological relevance of genetic risk factors for common age-related diseases: a proof of principle on type 2 diabetes.

    PubMed

    Garagnani, Paolo; Giuliani, Cristina; Pirazzini, Chiara; Olivieri, Fabiola; Bacalini, Maria Giulia; Ostan, Rita; Mari, Daniela; Passarino, Giuseppe; Monti, Daniela; Bonfigli, Anna Rita; Boemi, Massimo; Ceriello, Antonio; Genovese, Stefano; Sevini, Federica; Luiselli, Donata; Tieri, Paolo; Capri, Miriam; Salvioli, Stefano; Vijg, Jan; Suh, Yousin; Delledonne, Massimo; Testa, Roberto; Franceschi, Claudio

    2013-05-01

    Genetic association studies of age-related, chronic human diseases often suffer from a lack of power to detect modest effects. Here we propose an alternative approach of including healthy centenarians as a more homogeneous and extreme control group. As a proof of principle we focused on type 2 diabetes (T2D) and assessed /genotypic associations of 31 SNPs associated with T2D, diabetes complications and metabolic diseases and SNPs of genes relevant for telomere stability and age-related diseases. We hypothesized that the frequencies of risk variants are inversely correlated with decreasing health and longevity. We performed association analyses comparing diabetic patients and non-diabetic controls followed by association analyses with extreme phenotypic groups (T2D patients with complications and centenarians). Results drew attention to rs7903146 (TCF7L2 gene) that showed a constant increase in the frequencies of risk genotype (TT) from centenarians to diabetic patients who developed macro-complications and the strongest genotypic association was detected when diabetic patients were compared to centenarians (p_value = 9.066*10⁻⁷). We conclude that robust and biologically relevant associations can be obtained when extreme phenotypes, even with a small sample size, are compared.

  17. Recommendations for age-appropriate education of children and adolescents with diabetes and their parents in the European Union.

    PubMed

    Martin, Delphine; Lange, Karin; Sima, Alexandra; Kownatka, Dagmar; Skovlund, Søren; Danne, Thomas; Robert, Jean-Jacques

    2012-09-01

    Education is the keystone of diabetes care, and structured self-management education is the key to a successful outcome. Existing guidelines provide comprehensive guidance on the various aspects of education and offer general and organizational principles of education, detailed curricula at different ages and stages of diabetes, and recommendations on models, methods, and tools to attain educative objectives. The International Society for Pediatric and Adolescent Diabetes guidelines give the most elaborate and detailed descriptions and recommendations on the practice of education, which other national guidelines address on specific aspects of education and care. The aim of the work package on education developed by Better Control in Paediatric and Adolescent Diabetes in the European Union: Working to Create Centers of Reference (SWEET) project was not to generate new guidelines but to evaluate how the existing guidelines were implemented in some pediatric diabetes reference centers. The SWEET members have completed a questionnaire that elaborates on the many aspects of delivery of education. This survey highlights a profound diversity of practices across centers in Europe, in terms of organization as well as the practices and the content of initial and continuing education. A toolbox is being developed within SWEET to facilitate exchanges on all aspects of education and to establish a process of validation of materials, tools, written structured age-adjusted programs, and evaluation procedures for the education of children and adolescents with diabetes.

  18. Antioxidant capacity and structural changes of human serum albumin from patients in advanced stages of diabetic nephropathy and the effect of the dialysis.

    PubMed

    Rosas-Díaz, Marisol; Camarillo-Cadena, Menandro; Hernández-Arana, Andrés; Ramón-Gallegos, Eva; Medina-Navarro, Rafael

    2015-06-01

    Changes in the antioxidant capacity of albumin and alterations of the albumin structural conformation were examined in patients in advanced stages of diabetes nephropathy. Human serum albumin was purified from diabetic patients in pre-dialysis (glomerular filtration rate [GFR] between 15 and 29 ml min(-1) 1.73 m(-2)) and those in dialysis (GFR ≤ 15 ml min(-1) 1.73 m(-2)) and then compared with albumin from patients with a normal GFR (>90 ml min(-1) m(-2)). We evaluated the antioxidant capacity of albumin using an enhanced chemiluminescence-based assay and thiol group content, and the structural changes were evaluated by circular dichroism and fluorescence spectroscopy. The antioxidant capacity and thiol content of albumin from patients in advanced stages of diabetic nephropathy were markedly reduced. The circular dichroism spectra showed a mean albumin α-helix content reduction from 44 to 37 % and from 44 to 30 % between the control group and pre-dialysis and dialysis patients, respectively. Additionally, the fluorescence intensity was reduced by 4.2 and 13 % for the groups 4 and 5, respectively, in relation with the control. These data provide evidence for the partial denaturation of albumin and exacerbated oxidative stress among patients in advanced stages of diabetes nephropathy before and even after dialysis.

  19. Age of the crowfoot advance in the Canadian Rocky Mountains. A glacial event coeval with the Younger Dryas oscillation

    SciTech Connect

    Reasoner, M.A.; Rutter, N.W. ); Osborn, G. )

    1994-05-01

    A suite of sediment core samples was recovered from two lakes, Crowfoot and Bow lakes, that are adjacent to the Crowfoot moraine type locality, to identify and radiocarbon date sediments related to the Crowfoot advance. The Crowfoot moraine system, widely recognized throughout northwestern North America, represents a glacial advance that is post-Wisconsin and pre-Mazama tephra in age. An interval of inorganic sediments bracketed by accelerator mass spectrometry radiocarbon ages of ca. 11,330 and 10,100 [sup 14]C yr B.P. is associated with the Crowfoot moraine. The Crowfoot advance is therefore approximately synchronous with the European Younger Dryas cold event (ca. 11,000-10,000 [sup 14]C yr B.P.). Furthermore, the termination of the Crowfoot advance also appears to have been abrupt. These findings illustrate that the climatic change responsible for the European Younger Dryas event extended beyond the northern Atlantic basin and western Europe. Equilibrium-line altitude (ELA) depressions associated with the Crowfoot advance are similar to those determined for the Little Ice Age advance, whereas Younger Dryas ELA depressions in Europe significantly exceed Little Ice Age ELA depressions. 26 refs., 3 figs., 1 tab.

  20. Type 2 diabetes: genetic data sharing to advance complex disease research.

    PubMed

    Flannick, Jason; Florez, Jose C

    2016-09-01

    As with other complex diseases, unbiased association studies followed by physiological and experimental characterization have for years formed a paradigm for identifying genes or processes of relevance to type 2 diabetes mellitus (T2D). Recent large-scale common and rare variant genome-wide association studies (GWAS) suggest that substantially larger association studies are needed to identify most T2D loci in the population. To hasten clinical translation of genetic discoveries, new paradigms are also required to aid specialized investigation of nascent hypotheses. We argue for an integrated T2D knowledgebase, designed for a worldwide community to access aggregated large-scale genetic data sets, as one paradigm to catalyse convergence of these efforts. PMID:27402621

  1. Quantitative assessment of oscillatory components in blood circulation: classification of the effect of aging, diabetes, and acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Bernjak, Alan; Stefanovska, Aneta; Urbancic-Rovan, Vilma; Azman-Juvan, Katja

    2005-04-01

    The human cardiovascular system is a complex system with the pumping activity of the heart as the main generator of oscillations. Besides the heartbeat there are several other oscillatory components which determine its dynamics. Their nonlinear nature and a weak coupling between them both require special treatment while studying this system. A particular characteristic of the oscillatory components is their frequency fluctuations in time. Consequently, their interactions also fluctuate in time. Therefore the wavelet transform is applied to trace the oscillatory components in time, and specific quantitative measures are introduced to quantify the contribution of each of the oscillatory components involved on the time scale of up to three minutes. Oscillatory components are then analysed from signals obtained by simultaneous measurements of blood flow in the microcirculation, ECG, respiration and blood pressure. Based on quantitative evaluation of the oscillatory components related to (I) the heart beat (0.6-2Hz), (II) respiration (0.145-0.6Hz), (III) intrinsic myogenic activity (0.052-0.145Hz), (IV) sympathetic activity (0.021-0.052Hz), (V, VI) endothelial related activity (0.0095-0.021Hz, 0.005 - 0.0095 Hz), 30-minutes recording taken on 109 healthy subjects, 75 patients with diabetes, and 82 patients after acute myocardial infarction (AMI) were analysed. Classification of the effect of ageing, diabetes and AMI from blood flow signals simultaneously recorded in the skin of four extremities, the heart rate and heart rate variability from R-R intervals will be presented and discussed.

  2. A Priori Attitudes Predict Amniocentesis Uptake in Women of Advanced Maternal Age: A Pilot Study.

    PubMed

    Grinshpun-Cohen, Julia; Miron-Shatz, Talya; Rhee-Morris, Laila; Briscoe, Barbara; Pras, Elon; Towner, Dena

    2015-01-01

    Amniocentesis is an invasive procedure performed during pregnancy to determine, among other things, whether the fetus has Down syndrome. It is often preceded by screening, which gives a probabilistic risk assessment. Thus, ample information is conveyed to women with the goal to inform their decisions. This study examined the factors that predict amniocentesis uptake among pregnant women of advanced maternal age (older than 35 years old at the time of childbirth). Participants filled out a questionnaire regarding risk estimates, demographics, and attitudes on screening and pregnancy termination before their first genetic counseling appointment and were followed up to 24 weeks of gestation. Findings show that women's decisions are not always informed by screening results or having a medical indication. Psychological factors measured at the beginning of pregnancy: amniocentesis risk tolerance, pregnancy termination tolerance, and age risk perception affected amniocentesis uptake. Although most women thought that screening for Down syndrome risk would inform their decision, they later stated other reasons for screening, such as preparing for the possibility of a child with special needs. Findings suggest that women's decisions regarding amniocentesis are driven not only by medical factors, but also by a priori attitudes. The authors believe that these should be addressed in the dialogue on women's informed use of prenatal tests. PMID:26065331

  3. Advanced age brings a greater reliance on visual feedback to maintain balance during walking.

    PubMed

    Franz, Jason R; Francis, Carrie A; Allen, Matthew S; O'Connor, Shawn M; Thelen, Darryl G

    2015-04-01

    We implemented a virtual reality system to quantify differences in the use of visual feedback to maintain balance during walking between healthy young (n=12, mean age: 24 years) and healthy old (n=11, 71 years) adults. Subjects walked on a treadmill while watching a speed-matched, virtual hallway with and without mediolateral visual perturbations. A motion capture system tracked center of mass (CoM) motion and foot kinematics. Spectral analysis, detrended fluctuation analysis, and local divergence exponents quantified old and young adults' dynamic response to visual perturbations. Old and young adults walked normally with comparable CoM spectral characteristics, lateral step placement temporal persistence, and local divergence exponents. Perturbed visual flow induced significantly larger changes in mediolateral CoM motion in old vs. young adults. Moreover, visual perturbations disrupted the control of lateral step placement and compromised local dynamic stability more significantly in old than young adults. Advanced age induces a greater reliance on visual feedback to maintain balance during waking, an effect that may compensate for degradations in somatosensation. Our findings are relevant to the early diagnosis of sensory-induced balance impairments and also point to the potential use of virtual reality to evaluate sensory rehabilitation and balance training programs for old adults.

  4. Aging and a long-term diabetes mellitus increase expression of 1 α-hydroxylase and vitamin D receptors in the rat liver.

    PubMed

    Vuica, Ana; Ferhatović Hamzić, Lejla; Vukojević, Katarina; Jerić, Milka; Puljak, Livia; Grković, Ivica; Filipović, Natalija

    2015-12-01

    Diabetes mellitus (DM) is a metabolic disorder associated with serious liver complications. As a metabolic chronic disease, DM is very common in the elderly. Recent studies suggest ameliorating effects of vitamin D on metabolic and oxidative stress in the liver tissue in an experimental model of DM. The aim of this study was to investigate the expression of vitamin D receptors (VDRs) and 1α-hydroxylase, the key enzyme for the production of active vitamin D form (calcitriol) in the liver during long-term diabetes mellitus type 1 (DM1) in aging rats. We performed immunohistochemical analysis of liver expression of 1α-hydroxylase and VDRs during aging in long-term streptozotocin-induced DM1. 1α-Hydroxylase was identified in the monocyte/macrophage system of the liver. In addition to the nuclear expression, we also observed the expression of VDR in membranes of lipid droplets within hepatocytes. Aging and long-term DM1 resulted in significant increases in the number of 1α-hydroxylase immunoreactive cells, as well as the percentage of strongly positive VDR hepatocytes. In conclusion, the liver has the capacity for active vitamin D synthesis in its monocyte/macrophage system that is substantially increased in aging and long-term diabetes mellitus. These conditions are also characterized by significant increases in vitamin D receptor expression in hepatocytes. The present study suggests that VDR signaling system could be a potential target in prevention of liver complications caused by diabetes and aging.

  5. Variation in the UCP2-UCP3 gene cluster predicts the development of type 2 diabetes in healthy middle-aged men.

    PubMed

    Gable, David R; Stephens, Jefferey W; Cooper, Jackie A; Miller, George J; Humphries, Steve E

    2006-05-01

    The impact of the UCP2 -866G>A and UCP3 -55C>T variants on prospective risk of type 2 diabetes was examined over 15 years in 2,936 healthy middle-aged men (mean age 56 years). Conversion to diabetes (n = 169) was associated with higher BMI, blood pressure, cholesterol, triglycerides and C-reactive protein. The hazard ratio (HR) for diabetes of a BMI >30 kg/m(2) was 3.96 (95% CI 2.87-5.47). Homozygosity for the UCP2A or UCP3T alleles accelerated the onset of diabetes, with significant differences in risk of diabetes at 10 years (HR [95% CI] UCP2AA vs. GA+GG 1.94 [1.18-3.19], P = 0.009; UCP3TT vs. CC+ CT 2.06 [1.06-3.99], P = 0.03) but less so at 15 years (UCP2AA 1.42 [0.92-2.19], P = 0.1; UCP3TT 1.57 [0.87-2.04], P = 0.13). Men who were homozygous for both UCP2AA and UCP3TT (1.5% of men) had a risk for diabetes at 10 years of 4.20 (1.70-10.37), P = 0.002. These genotype effects were additive with obesity, and men with a BMI >30 kg/m(2) and this genotype combination had a 10-year risk of diabetes of 19.23 [5.63-63.69], P < 0.0001. Functional promoter variants UCP2 and UCP3 increase the prospective risk of diabetes. Although the mechanism of the UCP2 effect is likely to be caused by increased expression in the pancreas and subsequent reduced insulin secretion, the mechanism of the UCP3 effect is currently unknown. Both effects are exacerbated by obesity.

  6. Advanced life events (ALEs) that impede aging-in-place among seniors.

    PubMed

    Lindquist, Lee A; Ramirez-Zohfeld, Vanessa; Sunkara, Priya; Forcucci, Chris; Campbell, Dianne; Mitzen, Phyllis; Cameron, Kenzie A

    2016-01-01

    Despite the wishes of many seniors to age-in-place in their own homes, critical events occur that impede their ability to do so. A gap exists as to what these advanced life events (ALEs) entail and the planning that older adults perceive is necessary. The purpose of this study was to identify seniors' perceptions and planning toward ALEs that may impact their ability to remain in their own home. We conducted focus groups with 68 seniors, age ≥65 years (mean age 73.8 years), living in the community (rural, urban, and suburban), using open-ended questions about perceptions of future heath events, needs, and planning. Three investigators coded transcriptions using constant comparative analysis to identify emerging themes, with disagreements resolved via consensus. Subjects identified five ALEs that impacted their ability to remain at home: (1) Hospitalizations, (2) Falls, (3) Dementia, (4) Spousal Loss, and (5) Home Upkeep Issues. While recognizing that ALEs frequently occur, many subjects reported a lack of planning for ALEs and perceived that these ALEs would not happen to them. Themes for the rationale behind the lack of planning emerged as: uncertainty in future, being too healthy/too sick, offspring influences, denial/procrastination, pride, feeling overwhelmed, and financial concerns. Subjects expressed reliance on offspring for navigating future ALEs, although many had not communicated their needs with their offspring. Overcoming the reasons for not planning for ALEs is crucial, as being prepared for future home needs provides seniors a voice in their care while engaging key supporters (e.g., offspring). PMID:26952382

  7. Age- and Sex-related Prevalence and Drug Utilization Pattern in the Management of Type 2 Diabetes Mellitus and its Comorbidity with Cardiovascular Diseases: A Comparative Study.

    PubMed

    Das, S; Haroled Peter, P L; Bhavani, M Lakshmi; Naresh, P; Ramana, M V

    2015-01-01

    A cross-sectional study of 250 cases of type 2 diabetes management was conducted in a governmental tertiary care hospital of urban south India to determine the comparative prevalence of type 2 diabetes and its comorbidity with cardiovascular diseases in diabetic population, core drug use indicators and drug utilization pattern in the management of diabetics entirely and with cardiovascular diseases. Highest prevalent age group for type 2 diabetes/cardiovascular diseases (greater incidence in female than male) was 51-60 years. The 62.8% prevalence of cardiovascular diseases in the diabetic population ascertained in the study could provide an evidence-based rationale for the World Health Organization guidelines for the management of hypertension in type 2 diabetics. Incidence of polypharmacy (6.06, the mean number of total drug products prescribed); 59.26% of encounters prescribed antibiotics; 17.6 and 18.5 min of average consultation and dispensing time, respectively; 100% of drugs actually dispensed and adequately labeled; 81.26% of patients having knowledge of correct dosage and average drug cost of Indian Rupees 145.54 per prescription were the core drug use indicators found mainly. Moreover, drugs prescribed from the Essential Drug List were more than 90% and thereby indicated the drug use in this set-up quite rational. Around 71.09% of cardiovascular agents prescribed by generic name revealed the cost effective medical care. Among the agents in type 2 diabetes management, Actrapid(®) (35.43%) was the highest. Among the cardiovascular agents prescribed, lasix (19.37%) was the highest. Cardiovascular agents prescribed orally by 76.48% signified the good prescription habit indicating the improved patients' adherence to the treatment. The present study emphasizes the need of early detection of hypertension as a preliminary diagnostic parameter of cardiovascular diseases in diabetics and appropriate management through concomitant therapy of cardiovascular drugs to

  8. Age- and Sex-related Prevalence and Drug Utilization Pattern in the Management of Type 2 Diabetes Mellitus and its Comorbidity with Cardiovascular Diseases: A Comparative Study.

    PubMed

    Das, S; Haroled Peter, P L; Bhavani, M Lakshmi; Naresh, P; Ramana, M V

    2015-01-01

    A cross-sectional study of 250 cases of type 2 diabetes management was conducted in a governmental tertiary care hospital of urban south India to determine the comparative prevalence of type 2 diabetes and its comorbidity with cardiovascular diseases in diabetic population, core drug use indicators and drug utilization pattern in the management of diabetics entirely and with cardiovascular diseases. Highest prevalent age group for type 2 diabetes/cardiovascular diseases (greater incidence in female than male) was 51-60 years. The 62.8% prevalence of cardiovascular diseases in the diabetic population ascertained in the study could provide an evidence-based rationale for the World Health Organization guidelines for the management of hypertension in type 2 diabetics. Incidence of polypharmacy (6.06, the mean number of total drug products prescribed); 59.26% of encounters prescribed antibiotics; 17.6 and 18.5 min of average consultation and dispensing time, respectively; 100% of drugs actually dispensed and adequately labeled; 81.26% of patients having knowledge of correct dosage and average drug cost of Indian Rupees 145.54 per prescription were the core drug use indicators found mainly. Moreover, drugs prescribed from the Essential Drug List were more than 90% and thereby indicated the drug use in this set-up quite rational. Around 71.09% of cardiovascular agents prescribed by generic name revealed the cost effective medical care. Among the agents in type 2 diabetes management, Actrapid(®) (35.43%) was the highest. Among the cardiovascular agents prescribed, lasix (19.37%) was the highest. Cardiovascular agents prescribed orally by 76.48% signified the good prescription habit indicating the improved patients' adherence to the treatment. The present study emphasizes the need of early detection of hypertension as a preliminary diagnostic parameter of cardiovascular diseases in diabetics and appropriate management through concomitant therapy of cardiovascular drugs to

  9. Increasing burden, younger age at onset and worst metabolic control in migrant than in Italian children with type 1 diabetes: an emerging problem in pediatric clinics.

    PubMed

    Cadario, Francesco; Cerutti, Franco; Savastio, Silvia; Rabbone, Ivana; Tumini, Stefano; Bruno, Graziella

    2014-04-01

    To assess burden and clinical features of type 1 diabetes in migrant with respect to Italian children. Prevalent children with type 1 diabetes were identified through a multicenter study, including 46 pediatric outpatients diabetic clinics. A nested case-control study was also performed, comparing features at diabetes onset and after 1 year of insulin treatment in 84 migrants and 75 Italian children with onset in 2011, matched for age and sex. Out of 7,812 children cared for by pediatric diabetologists, 761 (10%) were migrant and 548 of them were born in Italy. Age at diagnosis was lower in migrants born in Italy (5.1 years, interquartile range (IQR) 2.2-7.7) than in those born in their original countries (7.8 years, IQR 5.3-10.3) and in Italians (9.8 years, IQR 5.9-13.0, p < 0.001). At diabetes onset, migrants had lower frequencies of positivities of markers of β-cell autoimmunity (96 vs. 99.5%, p < 0.01), higher values of weight loss (11 vs. 7%, p < 0.01), HbA1c (70 vs. 58 mmol/mol, p < 0.001), and insulin requirement (0.70 ± 0.03 vs. 0.63 ± 0.10 UI/kg/die, p = 0.05) and lower levels of 25-OH vitamin D3 (15.0 ± 2.8 vs. 20.8 ± 1.3, p = 0.03). Moreover, they experienced higher frequencies of hospitalizations during the first year of disease (19.2 vs. 2.7%, p < 0.001). Burden of type 1 diabetes in migrant children is increasing in Italy, with younger age at onset and different clinical features than in Italian children. Higher hospitalization rates and poorer glycemic control over the first year underline that approach to diabetes care in migrants needs to be improved. PMID:24065151

  10. Diabetes, Depressive Symptoms, and Inflammation in Older Adults: Results from the Health, Aging, and Body Composition Study

    PubMed Central

    Doyle, Todd A.; de Groot, Mary; Harris, Tamara; Schwartz, Frank; Strotmeyer, Elsa S.; Johnson, Karen C.; Kanaya, Alka

    2013-01-01

    Objective Up-regulated levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) are common to both type 2 diabetes mellitus (T2DM) and elevated depressive symptoms, yet little attention has been given to the biological mechanisms associated with these co-morbidities. This study examined the association between inflammation and both T2DM and elevated depressive symptoms. Methods Baseline data were analyzed from 3,009 adults, aged 70–79, participating in the Health, Aging, and Body Composition Study. Diabetes was assessed per self-report, medication use, fasting glucose and/or glucose tolerance tests. Elevated depressive symptoms were categorized using the Center for Epidemiologic Studies Depression scale (cut-score≥20). Log-transformed IL-6, TNF-α, and CRP were analyzed using ANCOVA. Results Participants with T2DM and elevated depressive symptoms (T2DM+DEP n=14) demonstrated significantly (p<.05) higher IL-6 compared to (T2DM Only n=628), (DEP Only n=49), and (No T2DM or DEP n=2,067) groups following covariate adjustment. Similarly, participants with T2DM+DEP (n=14) had significantly (p<.05) higher CRP, after covariate adjustment, compared to DEP Only (n=50) and No T2DM or DEP groups (n=2,153). No association was observed for TNF-α. Conclusions These findings provide evidence that inflammation is associated with T2DM and elevated depressive symptoms. Participants with T2DM+DEP demonstrated the highest IL-6 levels compared to all other groups. Greater CRP levels were also observed in T2DM, but not elevated depressive symptoms, which may suggest that differential associations between T2DM and depressive symptoms exist for various inflammatory markers. Further investigation into these associations could aid in understanding the biological pathways underlying both T2DM and depressive symptoms. PMID:24182629

  11. Pancreas transplant for diabetes mellitus.

    PubMed

    Kerr, Hannah R; Hatipoglu, Betul; Krishnamurthi, Venkatesh

    2015-11-01

    Pancreas transplant is an option for patients with type 1 diabetes and for some patients with type 2 diabetes and advanced diabetic kidney disease. The procedure has a high success rate, and performing it earlier in the course of diabetes could help prevent or reverse the long-term complications of diabetes.

  12. Dietary advanced glycation end products restriction diminishes inflammation markers and oxidative stress in patients with type 2 diabetes mellitus

    PubMed Central

    Luévano-Contreras, Claudia; Garay-Sevilla, Ma. Eugenia; Wrobel, Kazimierz; Malacara, Juan M.; Wrobel, Katarzyna

    2013-01-01

    The augmented consumption of dietary advanced glycation end products (dAGEs) has been associated with increased oxidative stress and inflammation, however, there is insufficient information over the effect on insulin resistance. The objective of the present study is to investigate the effect of dAGEs restriction on tumor necrosis factor-α (TNF-α), malondialdehyde, C-reactive protein (CRP), and insulin resistance in DM2 patients. We carried out a randomized 6 weeks prospective study in two groups of patients: subjects with a standard diet (n = 13), vs low dAGEs (n = 13). At the beginning and the end of study, we collected anthropometric measurements, and values of circulating glucose, HbA1c, lipids, insulin, serum AGEs, CRP, TNF-α and malondialdehyde. Anthropometric measurements, glucose, and lipids were similar in both groups at base line and at the end of the study. Estimation of basal dAGEs was similar in both groups; after 6 weeks it was unchanged in the standard group but in the low dAGEs group decreased by 44% (p<0.0002). Changes in TNF-α levels were different under standard diet (12.5 ± 14.7) as compared with low dAGEs (−18.36 ± 17.1, p<0.00001); changes in malondialdehyde were different in the respective groups (2.0 ± 2.61 and −0.83 ± 2.0, p<0.005) no changes were found for insulin levels or HOMA-IR. In conclusion, The dAGEs restriction decreased significantly TNF-α and malondialdehyde levels. PMID:23341693

  13. Dietary advanced glycation end products restriction diminishes inflammation markers and oxidative stress in patients with type 2 diabetes mellitus.

    PubMed

    Luévano-Contreras, Claudia; Garay-Sevilla, Ma Eugenia; Wrobel, Kazimierz; Malacara, Juan M; Wrobel, Katarzyna

    2013-01-01

    The augmented consumption of dietary advanced glycation end products (dAGEs) has been associated with increased oxidative stress and inflammation, however, there is insufficient information over the effect on insulin resistance. The objective of the present study is to investigate the effect of dAGEs restriction on tumor necrosis factor-α (TNF-α), malondialdehyde, C-reactive protein (CRP), and insulin resistance in DM2 patients. We carried out a randomized 6 weeks prospective study in two groups of patients: subjects with a standard diet (n = 13), vs low dAGEs (n = 13). At the beginning and the end of study, we collected anthropometric measurements, and values of circulating glucose, HbA1c, lipids, insulin, serum AGEs, CRP, TNF-α and malondialdehyde. Anthropometric measurements, glucose, and lipids were similar in both groups at base line and at the end of the study. Estimation of basal dAGEs was similar in both groups; after 6 weeks it was unchanged in the standard group but in the low dAGEs group decreased by 44% (p<0.0002). Changes in TNF-α levels were different under standard diet (12.5 ± 14.7) as compared with low dAGEs (-18.36 ± 17.1, p<0.00001); changes in malondialdehyde were different in the respective groups (2.0 ± 2.61 and -0.83 ± 2.0, p<0.005) no changes were found for insulin levels or HOMA-IR. In conclusion, The dAGEs restriction decreased significantly TNF-α and malondialdehyde levels.

  14. Age at type 2 diabetes onset and glycaemic control: results from the National Health and Nutrition Examination Survey (NHANES) 2005–2010

    PubMed Central

    Berkowitz, Seth A.; Meigs, James B.; Wexler, Deborah J.

    2013-01-01

    Aims/hypothesis We tested the hypothesis that age younger than 65 years at type 2 diabetes diagnosis is associated with worse subsequent glycaemic control. Methods A cross-sectional analysis of data from participants in the 2005–2010 National Health and Nutrition Examination Survey was performed. For adults with self-reported diabetes, we dichotomised age at diabetes diagnosis as younger (<65 years) vs older (≥65 years). The primary outcome of interest was HbA1c >9.0% (75 mmol/mol). Secondary outcomes were HbA1c >8.0% (64 mmol/mol) and >7.0% (53 mmol/mol). We used multivariable logistic regression for analysis. Results Among 1,438 adults with diabetes, a higher proportion of those <65 years at diagnosis compared with those ≥65 at diagnosis had an HbA1c >9.0% (14.4% vs 2.5%, p<0.001). After adjustment for sex, race/ethnicity, education, income, insurance, usual source of care, hyperglycaemia medication, duration of diabetes, family history, BMI and waist circumference, age <65 years at diagnosis remained significantly associated with greater odds of HbA1c > 9.0% (OR 3.22, 95% CI 1.54, 6.72), HbA1c > 8.0% (OR 2.72, 95% CI 1.43, 5.16) and HbA1c >7.0% (OR 1.92, 95% CI 1.18, 3.11). The younger group reported fewer comorbidities, but were less likely to report good health (OR 0.54, 95% CI 0.36, 0.83). Conclusions/interpretation Younger age at type 2 diabetes diagnosis is significantly associated with worse subsequent glycaemic control. Because patients who are younger at diagnosis have fewer competing comorbidities and complications, safe, aggressive, individualised treatment could benefit this higher-risk group. PMID:23995472

  15. Female reproductive dysfunction during ageing: role of methylglyoxal in the formation of advanced glycation endproducts in ovaries of reproductively-aged mice.

    PubMed

    Tatone, C; Carbone, M C; Campanella, G; Festuccia, C; Artini, P G; Talesa, V; Focarelli, R; Amicarelli, F

    2010-01-01

    Reproductive dysfunction with ageing has been so far extensively characterized in terms of depletion of ovarian follicles and reduced ability to produce gametes competent for fertilization. Nevertheless, molecular mechanisms underlying this process are still poorly understood. In the present study we addressed the hypothesis that methylglyoxal (MG), a major precursor of Advanced Glycation Endproducts (AGE), may contribute to molecular damage occurring during ovarian ageing. Our results showed that the biochemical activity of glyoxalase 1, the main component of the MG scavenging system, is significantly decreased in ovaries from reproductively-aged mice in comparison with the young group. This effect was associated with decreased expression at protein and RNA level of this enzyme and increased intraovarian level of MG. MG-arginine adducts argpyrimidine as detected with a specific antibody was found to accumulate with ageing in specific ovarian compartments. Separation of ovarian proteins by 2D gels and Western blotting revealed an approximate 30-fold increase in the extent of protein glycation in aged ovaries along with the appearance of eight argpyrimidine modified proteins exclusive for the aged group. In conclusion, the present results show that impaired MG detoxification causing relevant damage to the ovarian proteome might be one of the mechanisms underlying reproductive ageing and/or ageing-like ovarian diseases.

  16. High HDL-C prevalence is common in type 1 diabetes and increases with age but is lower in Hispanic individuals.

    PubMed

    Alessa, Thamer; Szeto, Angela; Chacra, Walid; Mendez, Armando; Goldberg, Ronald B

    2015-01-01

    High HDL-cholesterol (HDL-C) based on the 85th percentile of the 2009-2010 National Health and Education Survey (NHANES) was present in more than a third of 194 unselected subjects with type 1 diabetes (T1D). Age was associated with an increase and Hispanic ethnicity with a decrease in the prevalence of high HDL-C.

  17. Gestational Age, Infant Birth Weight, and Subsequent Risk of Type 2 Diabetes in Mothers: Nurses' Health Study II

    MedlinePlus

    ... Birth Weight, and Subsequent Risk of Type 2 Diabetes in Mothers: Nurses’ Health Study II Navigate This ... as 10 pounds or more at term. Gestational diabetes In the NHSII 1989 baseline questionnaire and subsequent ...

  18. Cost-Utility Analyses of Cataract Surgery in Advanced Age-Related Macular Degeneration

    PubMed Central

    Ma, Yingyan; Huang, Jiannan; Zhu, Bijun; Sun, Qian; Miao, Yuyu; Zou, Haidong

    2016-01-01

    ABSTRACT Purpose To explore the cost-utility of cataract surgery in patients with advanced age-related macular degeneration (AMD). Methods Patients who were diagnosed as having and treated for age-related cataract and with a history of advanced AMD at the Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, were included in the study. All of the participants underwent successful phacoemulsification with foldable posterior chamber intraocular lens implantation under retrobulbar anesthesia. Best-corrected visual acuity (BCVA) and utility value elicited by time trade-off method from patients at 3-month postoperative time were compared with those before surgery. Quality-adjusted life years (QALYs) gained in a lifetime were calculated at a 3% annual discounted rate. Costs per QALY gained were calculated using the bootstrap method, and probabilities of being cost-effective were presented using a cost-effectiveness acceptability curve. Sensitivity analyses were performed to test the robustness of the results. Results Mean logarithm of the minimum angle of resolution BCVA in the operated eye increased from 1.37 ± 0.5 (Snellen, 20/469) to 0.98 ± 0.25 (Snellen, 20/191) (p < 0.001); BCVA in the weighted average from both eyes (=75% better eye + 25% worse eye) was changed from 1.13 ± 0.22 (Snellen, 20/270) to 0.96 ± 0.17 (Snellen, 20/182) (p < 0.001). Utility values from both patients and doctors increased significantly after surgery (p < 0.001 and p = 0.007). Patients gained 1.17 QALYs by cataract surgery in their lifetime. The cost per QALY was 8835 Chinese yuan (CNY) (1400 U.S. dollars [USD]). It is cost-effective at the threshold of 115,062 CNY (18,235 USD) per QALY in China recommended by the World Health Organization. The cost per QALY varied from 7045 CNY (1116 USD) to 94,178 CNY (14,925 USD) in sensitivity analyses. Conclusions Visual acuity and quality of life assessed by utility value improved significantly after surgery

  19. Dating the Little Ice Age Advance of Jakobshavn Isbrae, Greenland, Using Pro-glacial Lake Sediments.

    NASA Astrophysics Data System (ADS)

    Stewart, H. A.; Briner, J. P.; Csatho, B. M.

    2009-05-01

    The Greenland Ice Sheet's (GIS) largest and fastest outlet glacier, Jakobshavn Isbrae, is one of the most significant contributors to GIS mass loss, draining an estimated 6.5% of the GIS area (Rignot and Kanagaratnam, 2006). Jakobshavn Isbrae has retreated significantly since the Little Ice Age (LIA, ca. 1250- 1900; Csatho et al., 2008), and continues to exhibit rapid changes in velocity and ice calving front position (Joughin et al., 2004). However, it is unknown for how long Jakobshavn Isbrae was at or near its extensive LIA position because there is a lack of chronological control on the LIA advance phase. We collected sediment cores from lakes just beyond the LIA margin to constrain the time when the advancing glacier's silt-laden meltwater entered the lake basins. Sediment cores from South Oval and Ice Boom lakes (informal names), which no longer receive glacial meltwater from Jakobshavn Isbrae because it has retreated out of their catchments, contain gyttja/glacial-silt/gyttja sequences that represent their non-glacial/pro-glacial/non-glacial histories. One additional site, ice-dammed Lake Morten (informal name), completely drained sometime between 1985 and 2001 AD. Outcrops of laminated sediments in the lake basin overly an intact tundra landscape. Four AMS radiocarbon dates from macrofossils immediately below the LIA sediments from the three lake basins reveal that Jakobshavn Isbrae reached its LIA maximum extent between 530±10 and 370±60 cal yr BP (1400-1640 AD). Furthermore, the continuous nature of the LIA-sediment units in all sites indicates that Jakobshavn Isbrae remained at or near its LIA maximum position between 1400-1640 AD and into the 20th century. Finally, pre-LIA organic-rich sediments at all sites continue uninterrupted down to basal sediments deposited during regional deglaciation in the Early Holocene. AMS radiocarbon ages on macrofossils from basal sediments at all sites range from 7220±40 to 8130±60 cal yr BP. We therefore interpret

  20. Diabetic Pets

    MedlinePlus

    ... made by a veterinarian. Because older dogs and cats are more likely to develop age-related diseases ... cataracts, which commonly develop in diabetic dogs and cats. Other problems that can occur include hind leg ...

  1. Association of vascular endothelial growth factor -634G/C and receptor for advanced glycation end products G82S gene polymorphisms with diabetic retinopathy

    PubMed Central

    Kamal, Asmaa; Abu Eleinen, Khaled; Siam, Ibrahem

    2016-01-01

    AIM To investigate the association of receptor for advanced glycation end products (RAGE) G82S and vascular endothelial growth factor (VEGF) -634 G/C gene polymorphisms with diabetic retinopathy (DR). METHODS Our cross-sectional study included 61 diabetic patients, 12 of them had proliferative diabetic retinopathy (PDR), 15 had non proliferative diabetic retinopathy (NPDR), 34 had no diabetic retinopathy (NDR) and 61 healthy controls. Participants were tested for RAGE G82S and VEGF -634 G/C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. RESULTS We found a significant association between VEGF -634 G/C polymorphism and PDR as PDR patients had increased incidence of VEGF -634 CC genotype compared to NDR patients [odds ratio for CC vs (GC+GG)=6.5, 95% CI=1.5-27.8, P=0.021]. Also VEGF -634 CC genotype and C allele were significantly higher in the PDR than in NPDR patients, which is a novel finding in our study (P=0.024, 0.009 respectively). The mean triglycerides level was significantly higher in diabetic patients with CC genotype (P=0.01) as compared to patients with other genotypes. All cases and control subjects were of the same heterozygous RAGE 82G/S genotype. CONCLUSION Patients carrying VEGF -634 C polymorphism have a higher risk of PDR development, so VEGF -634 G/C polymorphism could be used as a predictive marker for PDR in diabetic patients. We could not find a significant association between RAGE G82S polymorphism and DR. PMID:27588263

  2. How does diabetes accelerate Alzheimer disease pathology?

    PubMed

    Sims-Robinson, Catrina; Kim, Bhumsoo; Rosko, Andrew; Feldman, Eva L

    2010-10-01

    Diabetes and Alzheimer disease (AD)-two age-related diseases-are both increasing in prevalence, and numerous studies have demonstrated that patients with diabetes have an increased risk of developing AD compared with healthy individuals. The underlying biological mechanisms that link the development of diabetes with AD are not fully understood. Abnormal protein processing, abnormalities in insulin signaling, dysregulated glucose metabolism, oxidative stress, the formation of advanced glycation end products, and the activation of inflammatory pathways are features common to both diseases. Hypercholesterolemia is another factor that has received attention, owing to its potential association with diabetes and AD. This Review summarizes the mechanistic pathways that might link diabetes and AD. An understanding of this complex interaction is necessary for the development of novel drug therapies and lifestyle guidelines aimed at the treatment and/or prevention of these diseases.

  3. Age-dependent increases in tau phosphorylation in the brains of type 2 diabetic rats correlate with a reduced expression of p62.

    PubMed

    Jung, Hyun-Jung; Kim, Yoon-Jeong; Eggert, Simone; Chung, Kwang Chul; Choi, Kyeong Sook; Park, Sun Ah

    2013-10-01

    Aging increases the co-incidence of Alzheimer's disease (AD) and type 2 diabetes (T2DM). However, the critical factors that contribute to the age-related increase in AD-T2DM comorbidity have yet to be clarified. In this study, aging effects and their relationship to AD-related pathology and T2DM as well as the underlying mechanisms of this process were investigated using obese rats with chronic T2DM. Tau pathology and its associated signaling pathways in the brain were compared between Otsuka Long-Evans Tokushima Fatty (OLETF) rats and corresponding non-diabetic controls at various ages. Tau phosphorylation at AD-related epitopes, including Thr212, Thr231, Ser262, and Ser396, increased with age in the soluble brain extracts of chronic OLETF rats and were accompanied by synaptic protein loss. There was also a marked age-dependent accumulation of polyubiquitinated substances in diabetic rats. Accordingly, tau proteins were highly polyubiquitinated in aged OLETF rats and a strong degree of co-localization existed between p-tau and ubiquitin in these neurons. In addition, the mRNA and protein levels of p62, a known cargo molecule that transports polyubiquitinated tau to proteasomal and autophagic degradation systems, decreased robustly with age in OLETF rats and there was an inverse correlation between protein levels of p62 and p-tau. The impaired degradation of polyubiquitinated p-tau due to age- and T2DM-dependent decreases in p62 transcription is a primary mechanism underlying increased AD-like pathology in a T2DM rat model as age increases. These results provide novel insight into the mechanisms supporting the age-related increase in AD-T2DM comorbidity.

  4. Advanced paternal age increases the risk of schizophrenia and obsessive–compulsive disorder in a Chinese Han population

    PubMed Central

    Wu, Yuejing; Liu, Xiang; Luo, Hongrong; Deng, Wei; Zhao, Gaofeng; Wang, Qiang; Zhang, Lan; Ma, Xiaohong; Liu, Xiehe; Murray, Robin A.; Collier, David A.; Li, Tao

    2012-01-01

    Using the Structured Clinical Interview for DSM-IV, patient and non-patient version (SCID-P/NP), this study investigated 351 patients with schizophrenia, 122 with obsessive–compulsive disorder (OCD), and 238 unrelated healthy volunteers in a Chinese Han population. The relative risks posed by advanced paternal age for schizophrenia and OCD in offspring were computed under logistic regression analyses and adjusted for the participant's sex, age and co-parent age at birth. Compared to the offspring with paternal age of 25–29 years old, the relative risks rose from 2.660 to 10.183 in the paternal age range of 30–34 and ≥ 35. The relative risks for OCD increased from 2.225 to 5.413 in 30–34 and ≥ 35. For offspring with paternal age of < 25, the odds ratios of developing schizophrenia and OCD were 0.628 and 0.289 respectively, whereas an association between increased maternal age and risk for schizophrenia/OCD was not seen. Interaction analysis showed an interaction effect between paternal age and maternal age at birth. Such a tendency of risk affected by parental age for schizophrenia and OCD existed after splitting out the data of early onset patients. Sex-specific analyses found that the relative risks for schizophrenia with paternal age of 30–34 and ≥ 35 in male offspring were 2.407 and 10.893, and in female offspring were 3.080 and 9.659. The relative risks for OCD with paternal age of 30–34 and ≥ 35 in male offspring were 3.493 and 7.373, and in female offspring 2.005 and 4.404. The mean paternal age of schizophrenia/OCD patients born before the early 1980s was much greater than that of patients who were born after then. The findings illustrated that advanced paternal age is associated with increased risk for both schizophrenia and OCD in a Chinese Han population, prominently when paternal age is over 35. Biological and non-biological mechanisms may both be involved in the effects of advanced paternal age on schizophrenia and OCD. PMID

  5. Does advancing male age influence the expression levels and localisation patterns of phospholipase C zeta (PLCζ) in human sperm?

    PubMed Central

    Yeste, Marc; Jones, Celine; Amdani, Siti Nornadhirah; Yelumalai, Suseela; Mounce, Ginny; da Silva, Sarah J. Martins; Child, Tim; Coward, Kevin

    2016-01-01

    Socio-economic factors have led to an increasing trend for couples to delay parenthood. However, advancing age exerts detrimental effects upon gametes which can have serious consequences upon embryo viability. While such effects are well documented for the oocyte, relatively little is known with regard to the sperm. One fundamental role of sperm is to activate the oocyte at fertilisation, a process initiated by phospholipase C zeta (PLCζ), a sperm-specific protein. While PLCζ deficiency can lead to oocyte activation deficiency and infertility, it is currently unknown whether the expression or function of PLCζ is compromised by advancing male age. Here, we evaluate sperm motility and the proportion of sperm expressing PLCζ in 71 males (22–54 years; 44 fertile controls and 27 infertile patients), along with total levels and localisation patterns of PLCζ within the sperm head. Three different statistical approaches were deployed with male age considered both as a categorical and a continuous factor. While progressive motility was negatively correlated with male age, all three statistical models concurred that no PLCζ–related parameter was associated with male age, suggesting that advancing male age is unlikely to cause problems in terms of the sperm’s fundamental ability to activate an oocyte. PMID:27270687

  6. Effects of gender, age, and diabetes duration on dietary self-care in adolescents with type 1 diabetes: a Self-Determination Theory perspective.

    PubMed

    Austin, Stéphanie; Senécal, Caroline; Guay, Frédéric; Nouwen, Arie

    2011-09-01

    This study tests a model derived from Self-Determination Theory (SDT) (Deci and Ryan, 2000) to explain the mechanisms by which non-modifiable factors influence dietary self-care in adolescents with type 1 diabetes (n = 289). SEM analyses adjusted for HbA1c levels revealed that longer diabetes duration and female gender were indicative of poorer dietary self-care. This effect was mediated by contextual and motivational factors as posited by SDT. Poorer autonomy support from practitioners was predominant in girls with longer diabetes duration. Perceived autonomous motivation and self-efficacy were indicative of greater autonomy support, and led to better dietary self-care.

  7. [Effect of age on the prevalence of diabetes mellitus in Spain between 2001 and 2012].

    PubMed

    Jiménez Mejías, Eladio; Olvera Porcel, María C; Amezcua Prieto, Carmen; Olmedo-Requena, Rocío; Martínez Ruiz, Virginia; Jiménez Moleón, José Juan

    2014-06-01

    Objetivo: Valorar el efecto de la edad sobre el incremento en la prevalencia de DM en España entre 2001 y 2012. Métodos: Partiendo de las prevalencias de DM de las Encuestas Nacionales de Salud realizadas en España en 2001, 2006 y 2012 y de la distribución etaria de la población, se calcularon, mediante método directo, las prevalencias ajustadas por edad para cada año, tomando como población de referencia la de 2006. Asimismo, se calcularon los incrementos porcentuales crudos y ajustados para el periodo total y para los subperíodos 2001-2006 y 2006-2012. Resultados: El 12,5% del incremento en la prevalencia cruda de DM es atribuible al envejecimiento poblacional durante el período total. Aunque las tendencias son diferentes en los dos subperíodos considerados, las prevalencias ajustadas también muestran una tendencia creciente. Conclusiones: Además del envejecimiento poblacional, existen otros factores responsables del incremento en las tasas de diabetes en España en 2001-2012 que es preciso conocer.

  8. Diabetes mellitus Type II and cognitive capacity in healthy aging, mild cognitive impairment and Alzheimer's disease.

    PubMed

    Degen, Christina; Toro, Pablo; Schönknecht, Peter; Sattler, Christine; Schröder, Johannes

    2016-06-30

    While diabetes mellitus (DM) Type II has repeatedly been linked to Alzheimer´s disease (AD) and mild cognitive impairment (MCI), longitudinal research is scarce and disease duration has not always been taken into account. In a birth cohort born between 1930 and 1932 we investigated the influence of DM Type II and disease duration on neuropsychological functioning (memory/learning, attention, verbal fluency, visuospatial thinking and abstract thinking) across 14 years. Subjects who developed MCI or AD performed significantly poorer on all neuropsychological tests applied. While significant main effects DM Type II did not arise, its presence led to a significant deterioration of performance in the digit symbol test and visuospatial thinking over time. Additionally, in visuospatial thinking this change was more pronounced for individuals suffering from MCI/AD. We found that, as a concomitant disease DM Type II does not affect memory functioning, which is typically compromised in MCI and early AD. Rather, it may lead to deficits in cognitive flexibility and visuospatial thinking. DM Type II can be considered a frequent comorbid condition which can aggravate the course of MCI and AD. In this respect it may serve as a model for other comorbid conditions in AD. PMID:27082868

  9. Diabetes mellitus Type II and cognitive capacity in healthy aging, mild cognitive impairment and Alzheimer's disease.

    PubMed

    Degen, Christina; Toro, Pablo; Schönknecht, Peter; Sattler, Christine; Schröder, Johannes

    2016-06-30

    While diabetes mellitus (DM) Type II has repeatedly been linked to Alzheimer´s disease (AD) and mild cognitive impairment (MCI), longitudinal research is scarce and disease duration has not always been taken into account. In a birth cohort born between 1930 and 1932 we investigated the influence of DM Type II and disease duration on neuropsychological functioning (memory/learning, attention, verbal fluency, visuospatial thinking and abstract thinking) across 14 years. Subjects who developed MCI or AD performed significantly poorer on all neuropsychological tests applied. While significant main effects DM Type II did not arise, its presence led to a significant deterioration of performance in the digit symbol test and visuospatial thinking over time. Additionally, in visuospatial thinking this change was more pronounced for individuals suffering from MCI/AD. We found that, as a concomitant disease DM Type II does not affect memory functioning, which is typically compromised in MCI and early AD. Rather, it may lead to deficits in cognitive flexibility and visuospatial thinking. DM Type II can be considered a frequent comorbid condition which can aggravate the course of MCI and AD. In this respect it may serve as a model for other comorbid conditions in AD.

  10. Bone Aging by Advanced Glycation End Products: A Multiscale Mechanical Analysis.

    PubMed

    Ganeko, K; Masaki, C; Shibata, Y; Mukaibo, T; Kondo, Y; Nakamoto, T; Miyazaki, T; Hosokawa, R

    2015-12-01

    The quality and quantity of mandibular bone are essential prerequisites for osseointegrated implants. Only the Hounsfield unit on preoperative computed tomography is currently used as a clinical index. Nevertheless, a considerable mismatch occurs between bone quality and the Hounsfield unit. Loss of bone toughness during aging has been accepted based on empirical evidence, but this concept is unlikely evidence based at the level of mechanical properties. Nonenzymatic bone matrix cross-links associated with advanced glycation end products predominate as a consequence of aging. Thus, loss of tissue integrity could diminish the bone toughening mechanism. Here, we demonstrate an impaired bone toughening mechanism caused by mimicking aging in rabbits on a methionine-rich diet, which enabled an enhanced nonenzymatically cross-linked bone matrix. A 3-point bending test revealed a greater reduction in femoral fracture resistance in rabbits on a methionine-rich diet, despite higher maximum and normalized breaking forces (287.3 N and 88.1%, respectively), than in rabbits on a normal diet (262.2 N and 79.7%, respectively). In situ nanoindentation on mandibular cortical bone obtained from rabbits on a methionine-rich diet did not enable strain rate-dependent stiffening and consequent large-dimensional recovery during rapid loading following constant displacement after a rapid-load indentation test as compared with those in rabbits on a normal diet. Such nanoscale structure-function relationships dictate resistance to cracking propagation at the material level and allow for the overall bone toughening mechanism to operate under large external stressors. The strain-dependent stiffening was likely associated with strain-energy transfer to the superior cross-linked bone matrix network of the normal diet, while the reduction in the enzymatically cross-linked matrix in bone samples from rabbits on a methionine-rich diet likely diminished the intrinsic bone toughening mechanism. The

  11. Altered serum glyceraldehyde-derived advanced glycation end product (AGE) and soluble AGE receptor levels indicate carbonyl stress in patients with schizophrenia.

    PubMed

    Takeda, Mayu; Ohnuma, Tohru; Takeuchi, Masayoshi; Katsuta, Narimasa; Maeshima, Hitoshi; Takebayashi, Yuto; Higa, Motoyuki; Nakamura, Toru; Nishimon, Shohei; Sannohe, Takahiro; Hotta, Yuri; Hanzawa, Ryo; Higashiyama, Ryoko; Shibata, Nobuto; Gohda, Tomohito; Suzuki, Yusuke; Yamagishi, Sho-ichi; Tomino, Yasuhiko; Arai, Heii

    2015-04-23

    Recent cross-sectional and longitudinal studies indicate that measurements of peripheral blood carbonyl stress markers such as the advanced glycation end product (AGE) pentosidine and the reactive carbonyl-detoxifying B6 vitamin pyridoxal could be used as therapeutic biological markers in subpopulations of schizophrenia patients. Glyceraldehyde-derived AGEs (Glycer-AGE) have strong neurotoxicity, and soluble receptors for AGEs (sRAGE) may ameliorate the effects of AGEs. In the present study, we measured Glycer-AGEs and sRAGE levels to determine their potential as diagnostic, therapeutic, or clinical biological markers in patients with schizophrenia. After enrollment of 61 admitted Japanese patients with acute schizophrenia and 39 healthy volunteers, 54 patients were followed up from the acute stage to remission. Serum biomarkers were measured in blood samples taken before breakfast using competitive enzyme-linked immunosorbent assays, and Glycer-AGEs were significantly higher and sRAGE levels were significantly lower in patients with acute schizophrenia than in healthy controls. Glycer-AGEs/sRAGE ratios were also higher in schizophrenia patients and were stable during the clinical course. Furthermore, discriminant analyses confirmed that Glycer-AGEs and Glycer-AGEs/sRAGE ratios are significant diagnostic markers for schizophrenia, and distinguished between patients and healthy controls in 70.0% of cases. However, these markers of carbonyl stress were not correlated with clinical features, including disease severity, or with daily chlorpromazine doses. These data indicate the potential of Glycer-AGEs, RAGEs, and their relative ratios as diagnostic markers for patients with schizophrenia.

  12. Normative Scores and Factor Structure of the Profile of Mood States for Women Seeking Prenatal Diagnosis for Advanced Maternal Age.

    ERIC Educational Resources Information Center

    Tunis, Sandra L.; And Others

    1990-01-01

    A sample of pregnant women (N=705) was given the monopolar version of the Profile of Mood States (POMS) in prenatal counseling for advanced maternal age to develop normative data and to determine the factor structure of the POMS for this group of women in the first trimester of pregnancy. (SLD)

  13. The Social Structuring of Mental Health over the Adult Life Course: Advancing Theory in the Sociology of Aging

    ERIC Educational Resources Information Center

    Clarke, Philippa; Marshall, Victor; House, James; Lantz, Paula

    2011-01-01

    The sociology of aging draws on a broad array of theoretical perspectives and social theories from several disciplines, but rarely has it developed its own theories or theoretical perspectives. We build on past work to further advance and empirically test a model of mental health framed in terms of structural theorizing and situated within the…

  14. Back Translation: An Emerging Sophisticated Cyber Strategy to Subvert Advances in "Digital Age" Plagiarism Detection and Prevention

    ERIC Educational Resources Information Center

    Jones, Michael; Sheridan, Lynnaire

    2015-01-01

    Advances have been made in detecting and deterring the student plagiarism that has accompanied the uptake and development of the internet. Many authors from the late 1990s onwards grappled with plagiarism in the digital age, presenting articles that were provoking and established the foundation for strategies to address cyber plagiarism, including…

  15. Incidence of type 1 (insulin-dependent) diabetes mellitus in subjects 0-14 years of age in the Comunidad of Madrid, Spain.

    PubMed

    Serrano Ríos, M; Moy, C S; Martín Serrano, R; Minuesa Asensio, A; de Tomás Labat, M E; Zarandieta Romero, G; Herrera, J

    1990-07-01

    A retrospective, population-based registry was established in the Comunidad of Madrid, Spain (total population: 4,780,572; under age 15: 1,105,243) to investigate the epidemiology of Type 1 (insulin-dependent) diabetes mellitus. Included were all cases diagnosed with diabetes between 1985 and 1988, with age onset less than 15 years, and using insulin at discharge from hospital. Using the capture-recapture method employing hospital records as the primary source and membership files of the Spanish Diabetic Association as the secondary source, the ascertainment was 90%. The overall annual incidence was estimated to be 11.3/100,000 (Poison 95% confidence interval: 10.3-12.4). There was no temporal increase in incidence, nor was there a significant sex difference in incidence rates, either overall or by year. The seasonal onset pattern showed the highest incidence in winter (December-February) and lowest in summer (June-August) (r = 7.36, p less than 0.05). The age-adjusted (world standard) incidence of 10.9/100,000 was inconsistent with the hypothesis of a north-south gradient in diabetes risk.

  16. Advancing Paternal Age Is Associated with Deficits in Social and Exploratory Behaviors in the Offspring: A Mouse Model

    PubMed Central

    Mill, Jonathan; Fernandes, Cathy; Schalkwyk, Leonard C.; Buxbaum, Joseph D.; Reichenberg, Abraham

    2009-01-01

    Background Accumulating evidence from epidemiological research has demonstrated an association between advanced paternal age and risk for several psychiatric disorders including autism, schizophrenia and early-onset bipolar disorder. In order to establish causality, this study used an animal model to investigate the effects of advanced paternal age on behavioural deficits in the offspring. Methods C57BL/6J offspring (n = 12 per group) were bred from fathers of two different ages, 2 months (young) and 10 months (old), and mothers aged 2 months (n = 6 breeding pairs per group). Social and exploratory behaviors were examined in the offspring. Principal Findings The offspring of older fathers were found to engage in significantly less social (p = 0.02) and exploratory (p = 0.02) behaviors than the offspring of younger fathers. There were no significant differences in measures of motor activity. Conclusions Given the well-controlled nature of this study, this provides the strongest evidence for deleterious effects of advancing paternal age on social and exploratory behavior. De-novo chromosomal changes and/or inherited epigenetic changes are the most plausible explanatory factors. PMID:20041141

  17. Using technology to advance type 1 diabetes care among women during the reproductive years and in pregnancy.

    PubMed

    Polsky, Sarit; Giordano, Dominique; Voelmle, Mary K; Garcetti, Rachel; Garg, Satish K

    2016-05-01

    The prevalence of diabetes is increasing globally. Technology to improve care among individuals with diabetes is constantly being developed. Women living with Type 1 Diabetes Mellitus (T1DM) have unique challenges affecting their glucose control relating to menstrual cycles, pregnancy, and menopause. The purpose of this review is to examine the literature related to the use of technology to help women with T1DM manage their diabetes during the reproductive years, pregnancy, and beyond. Continuous subcutaneous insulin infusion (CSII) therapy can provider equivalent or better glucose control when compared with multiple daily injections (MDI), with less hypoglycemia, diabetic ketoacidosis, and weight gain. The CSII therapy has features that could help improve glucose control over the menstrual cycle, menopause, and pregnancy, although the most studied of these stages is pregnancy. Continuous glucose monitoring (CGM) can be combined with any insulin delivery system (MDI or CSII) to provide data on glucose values every few minutes and show glucose trends over time. CGM introduction can highlight glucose variability for women with T1DM, may be beneficial during pregnancy, and can reduce hypoglycemia. Sensor-augmented pump therapy and hybrid artificial pancreas (closed-loop) systems are promising tools that improve outcomes among individuals with diabetes. The use of modern technology to improve glucose and metabolic control among menopausal women with diabetes has not been well studied. Internet and phone-based technologies are emerging as important tools that may help with diabetes self-care for women living with diabetes. PMID:26924774

  18. Age- and Sex-Specific Relationships between Household Income, Education, and Diabetes Mellitus in Korean Adults: The Korea National Health and Nutrition Examination Survey, 2008-2010

    PubMed Central

    Kim, So-Ra; Han, Kyungdo; Choi, Jin-Young; Ersek, Jennifer; Liu, Junxiu; Jo, Sun-Jin; Lee, Kang-Sook; Yim, Hyeon Woo; Lee, Won-Chul; Park, Yong Gyu; Lee, Seung-Hwan; Park, Yong-Moon

    2015-01-01

    Background To investigate the effects of age and sex on the relationship between socioeconomic status (SES) and the prevalence and control status of diabetes mellitus (DM) in Korean adults. Methods Data came from 16,175 adults (6,951 men and 9,227 women) over the age of 30 who participated in the 2008-2010 Korea National Health and Nutrition Examination Survey. SES was measured by household income or education level. The adjusted odds ratios (ORs) and corresponding 95% confidence intervals (95% CI) for the prevalence or control status of diabetes were calculated using multiple logistic regression analyses across household income quartiles and education levels. Results The household income-DM and education level-DM relationships were significant in younger age groups for both men and women. The adjusted ORs and 95% CI for diabetes were 1.51 (0.97, 2.34) and 2.28 (1.29, 4.02) for the lowest vs. highest quartiles of household income and education level, respectively, in women younger than 65 years of age (both P for linear trend < 0.05 with Bonferroni adjustment). The adjusted OR and 95% CI for diabetes was 2.28 (1.53, 3.39) for the lowest vs. highest quartile of household income in men younger than 65 (P for linear trend < 0.05 with Bonferroni adjustment). However, in men and women older than 65, no associations were found between SES and the prevalence of DM. No significant association between SES and the status of glycemic control was detected. Conclusions We found age- and sex-specific differences in the relationship of household income and education with the prevalence of DM in Korea. DM preventive care is needed for groups with a low SES, particularly in young or middle-aged populations. PMID:25622031

  19. Effects of advancing age on the hypothalamic-pituitary-ovarian axis of the female white-footed mouse (Peromyscus leucopus).

    PubMed

    Steger, R W; Peluso, J J; Huang, H H; Hodson, C A; Leung, F C; Meites, J; Sacher, G

    1980-08-01

    Peromyscus leucopus, with an average lifespan of 48 months, showed unchanged levels of serum luteinizing hormone (LH), estradiol, progesterone, and pituitary LH and prolactin, between the ages of 12 and 48 months. Hypothalamic LH-releasing hormone (LHRH), norepinephrine and dopamine also remained unchanged with advancing age. Ovarian and uterine weight decreased with age, although the changes in uterine weight were not statistically significant. These data indicate that the hypothalamic-pituitary-ovarian axis remains intact with increasing age, accounting for the maintenance of fertility in these animals. The lack of significant changes in these parameters is in very marked contrast to those in the aging laboratory mouse and rat, which show derangements in their reproductive systems midway through their lifespans.

  20. Oxidative Stress and Adipocyte Biology: Focus on the Role of AGEs

    PubMed Central

    Boyer, Florence; Vidot, Jennifer Baraka; Dubourg, Alexis Guerin; Rondeau, Philippe; Essop, M. Faadiel

    2015-01-01

    Diabetes is a major health problem that is usually associated with obesity, together with hyperglycemia and increased advanced glycation endproducts (AGEs) formation. Elevated AGEs elicit severe downstream consequences via their binding to receptors of AGEs (RAGE). This includes oxidative stress and oxidative modifications of biological compounds together with heightened inflammation. For example, albumin (major circulating protein) undergoes increased glycoxidation with diabetes and may represent an important biomarker for monitoring diabetic pathophysiology. Despite the central role of adipose tissue in many physiologic/pathologic processes, recognition of the effects of greater AGEs formation in this tissue is quite recent within the obesity/diabetes context. This review provides a brief background of AGEs formation and adipose tissue biology and thereafter discusses the impact of AGEs-adipocyte interactions in pathology progression. Novel data are included showing how AGEs (especially glycated albumin) may be involved in hyperglycemia-induced oxidative damage in adipocytes and its potential links to diabetes progression. PMID:25878764

  1. Physiological responses and RPE during underwater treadmill walking in women of middle and advanced age.

    PubMed

    Shono, T; Fujishima, K; Hotta, N; Ogaki, T; Ueda, T; Otoki, K; Teramoto, K; Shimizu, T

    2000-07-01

    The purpose of this study was to examine the physiological responses and RPE during water walking using the Flowmill, which has a treadmill at the base of a water flume, in order to obtain basic data for prescribing water walking for people of middle and advanced age. Twenty healthy female volunteers with an age of 59.1 +/- 5.2 years took part in this study. They belonged to the same swimming club and regularly swam and exercised in water. Walking in water took place in the Flowmill. Subjects completed four consecutive bouts of 4 min duration at progressively increasing speeds (20, 30, 40 and 50 m/min) with 1 min rest between each bout. In addition, water velocity was adjusted to the walking speed of each bout. Subjects were instructed to swing both arms in order to maintain their balance during walking in water. The water depth was to the level of the xiphoid process and the water temperature was 30.31 +/- 0.08 degrees C. Both heart rate (HR) and oxygen uptake (VO2) increased exponentially as walking speed increased. HR was 125 +/- 15 bpm, and VO2 was 18.10 +/- 2.72 ml/kg.min-1 during walking in water at 50 m/min, which was the highest speed. The exercise intensity at this speed was equivalent to 5.2 +/- 0.8 Mets. The relationship between HR and VO2 during walking in water showed a highly significant linear relationship in each subject. There was also a highly significant linear relationship in the mean HR and VO2 of all subjects. Blood lactate concentration (LA) measured at rest and immediately after each bout was 1.1 +/- 0.4 mmol/l at rest, 1.0 +/- 0.2 mmol/l at 20 m/min, 1.0 +/- 0.3 mmol/l at 30 m/min, 1.1 +/- 0.2 mmol/l at 40 m/min, and 2.4 +/- 0.7 mmol/l at 50 m/min. LA at 50 m/min was significantly higher than at rest and at the other speeds. The relationship between HR and RPE during walking in water showed a highly significant linear relationship. The relationship between walking speed and energy expenditure calculated from VO2 and the respiratory exchange

  2. Which health-relate