JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2007
Ana Belén Navarro-Sanchez
Abstract Objetives: The purpose of this study was to compare the local efficacy of nonsurgical periodontal therapy between type 2 diabetic and non-diabetic patients and the effect of periodontal therapy on glycaemic control. Background: A complex two-way relationship exists between diabetes mellitus and periodontitis. Material and Methods: After selection, 20 subjects (10 diabetic and 10 non-diabetic) underwent baseline examination, periodontal clinical study and biochemical analysis of gingival crevicular fluid (GCF). After the pre-treatment phase, subgingival scaling and root planing were performed. Subsequently, all subjects continued the maintenance programme and were re-examined at 3 and 6 months. Results: Diabetic and non-diabetic subjects responded well after therapy, showing a very similar progression during the follow-up period. Both groups showed clinically and immunologically significant improvements. Significant reductions were also found in the total volume of GCF and levels of interleukin-1, and tumour necrosis factor- ,. Diabetic subjects showed an improvement in their metabolic control. The change in glycosylated haemoglobin (HbA1C) was statistically significant at 3 and 6 months. Conclusions: The clinical and immunological improvements obtained were accompanied by a significant reduction in HbA1C values in type 2 diabetic subjects. Larger studies are needed to confirm this finding and establish whether periodontal therapy has a significant effect on glycaemic control. [source]

The assessment of regional gut transit times in healthy controls and patients with gastroparesis using wireless motility technology

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010
I. SAROSIEK
Summary Background, Wireless pH and pressure motility capsule (wireless motility capsule) technology provides a method to assess regional gastrointestinal transit times. Aims, To analyse data from a multi-centre study of gastroparetic patients and healthy controls and to compare regional transit times measured by wireless motility capsule in healthy controls and gastroparetics (GP). Methods, A total of 66 healthy controls and 34 patients with GP (15 diabetic and 19 idiopathic) swallowed wireless motility capsule together with standardized meal (255 kcal). Gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT) and whole gut transit time (WGTT) were calculated using the wireless motility capsule. Results, Gastric emptying time, CTT and WGTT but not SBTT were significantly longer in GP than in controls. Eighteen percent of gastroparetic patients had delayed WGTT. Both diabetic and idiopathic aetiologies of gastroparetics had significantly slower WGTT (P < 0.0001) in addition to significantly slower GET than healthy controls. Diabetic gastroparetics additionally had significantly slower CTT than healthy controls (P = 0.0054). Conclusions, In addition to assessing gastric emptying, regional transit times can be measured using wireless motility capsule. The prolongation of CTT in gastroparetic patients indicates that dysmotility beyond the stomach in GP is present, and it could be contributing to symptom presentation. Aliment Pharmacol Ther,31, 313,322 [source]

Diabetic and nondiabetic lumbosacral radiculoplexus neuropathies: New insights into pathophysiology and treatment

MUSCLE AND NERVE, Issue 4 2002
P. James B. Dyck MD
Abstract Diabetic lumbosacral radiculoplexus neuropathy (DLRPN) (also called diabetic amyotrophy) is a well-recognized subacute, painful, asymmetric lower-limb neuropathy that is associated with weight loss and type II diabetes mellitus. Nondiabetic lumbosacral radiculoplexus neuropathy (LRPN) has received less attention. Comparison of large cohorts with DLRPN and LRPN demonstrated that age at onset, course, type and distribution of symptoms and impairments, laboratory findings, and outcomes are similar. Both conditions are lumbosacral radiculoplexus neuropathies that are associated with weight loss and begin focally with pain but that evolve into widespread, bilateral paralytic disorders. Although both are monophasic illnesses, patients have prolonged morbidity from pain and weakness, and many patients become wheelchair-dependent. Although motor-predominant, there is unequivocal evidence that autonomic and sensory nerves are also involved. Cutaneous nerves from patients with DLRPN and LRPN show pathological evidence of ischemic injury (multifocal fiber loss, perineurial thickening and degeneration, neovascularization, microfasciculation, and swollen axons with accumulated organelles) and microvasculitis (mural and perivascular inflammation, separation and fragmentation of mural smooth muscle layers of microvessels and hemosiderin-laden macrophages). Controlled trials with immune-modulating therapies in DLRPN are in progress, and preliminary data suggest that such therapy may be beneficial in LRPN. It is likely that DLRPN and LRPN are immune-mediated neuropathies that should be separated from chronic inflammatory demyelinating polyneuropathy and from systemic necrotizing vasculitis. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000,000, 2002 [source]

ORIGINAL ARTICLE: Glycation Endproducts, Soluble Receptor for Advanced Glycation Endproducts and Cytokines in Diabetic and Non-diabetic Pregnancies

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2009
Magdalena Perty, ska-Marczewska
Problem, Cytokines, advanced glycation end products (AGEs), and their receptor RAGE have been recently suggested to play a role in human pregnancy. In this study, we sought to determine the alterations of plasma AGEs, soluble RAGE (sRAGE), and proinflammatory cytokines in normal pregnancies and those complicated with type 1 diabetes mellitus. Method of study, These parameters were measured in samples from healthy non-pregnant (C), diabetic non-pregnant (D), healthy pregnant (HP), and pregnant diabetic (DP) women. Results, In the first trimester, DP showed lower sRAGE and higher AGEs compared to HP. In the DP group, significant negative correlations were seen between TNF-, and lipopolysaccharide (LPS)-stimulated ,L-6 in the first trimester and sRAGE in the third trimester. LPS-stimulated IL-12 was positively correlated with levels of AGEs in the third trimester. Conclusion, We detected several differences in the levels of AGEs, sRAGE, and proinflammatory cytokines between euglycemic and diabetic pregnancies. [source]

Caspase-1/interleukin-1beta signaling in diabetic retinopathy

ACTA OPHTHALMOLOGICA, Issue 2008
S MOHR
Purpose The pro-inflammatory cytokine, interleukin-1, (IL-1,), is known to induce vascular dysfunction and cell death. Previously, we have shown that caspase-1 activity is increased in retinas of diabetic and galactosemic mice, and diabetic patients. Therefore, we investigated the role of IL-1, and caspase-1 (the enzyme that produces it) in diabetes-induced degeneration of retinal capillaries. Methods First, we determined the effect of agents known to inhibit caspase-1 (minocycline and tetracycline) on IL-1, production and retinal capillary degeneration in diabetic and galactose-fed mice. Diabetic and galactose-fed mice were injected intraperitoneally with minocycline or tetracycline (5mg/kg). Second, we examined the effect of genetic deletion of the IL-1, receptor on diabetes-induced caspase activities and retinal capillary degeneration using IL-1 receptor knock-out mice. Results At 2 months of diabetes, minocycline inhibited hyperglycemia-induced caspase-1 activity and IL-1, production in the retina. Long-term administration of minocycline prevented retinal capillary degeneration in diabetic (6 months) and galactose-fed (13 months) mice. Tetracycline inhibited hyperglycemia-induced caspase-1 activity in vitro, but not in vivo. Mice deficient in the IL-1, receptor were protected from diabetes-induced caspase activation and retinal pathology at 7 months of diabetes. Conclusion These results indicate that the caspase-1/IL-1, signaling pathway plays an important role in diabetes-induced retinal pathology and its inhibition might represent a new strategy to inhibit capillary degeneration in diabetic retinopathy. [source]

Impaired cardiac functional reserve in type 2 diabetic db/db mice is associated with metabolic, but not structural, remodelling

ACTA PHYSIOLOGICA, Issue 1 2010
A. Daniels
Abstract Aim:, To identify the initial alterations in myocardial tissue associated with the early signs of diabetic cardiac haemodynamic dysfunction, we monitored changes in cardiac function, structural remodelling and gene expression in hearts of type 2 diabetic db/db mice. Methods:, Cardiac dimensions and function were determined echocardiographically at 8, 12, 16 and 18 weeks of age. Left ventricular pressure characteristics were measured at 18 weeks under baseline conditions and upon dobutamine infusion. Results:, The db/db mice were severely diabetic already at 8 weeks after birth, showing elevated fasting blood glucose levels and albuminuria. Nevertheless, echocardiography revealed no significant changes in cardiac function up to 18 weeks of age. At 18 weeks of age, left ventricular pressure characteristics were not significantly different at baseline between diabetic and control mice. However, dobutamine stress test revealed significantly attenuated cardiac inotropic and lusitropic responses in db/db mice. Post-mortem cardiac tissue analyses showed minor structural remodelling and no significant changes in gene expression levels of the sarcoplasmic reticulum calcium ATPase (SERCA2a) or ,1-adrenoceptor (,1-AR). Moreover, the phosphorylation state of known contractile protein targets of protein kinase A (PKA) was not altered, indicating unaffected cardiac ,-adrenergic signalling activity in diabetic animals. By contrast, the substantially increased expression of uncoupling protein-3 (UCP3) and angiopoietin-like-4 (Angptl4), along with decreased phosphorylation of AMP-activated protein kinase (AMPK) in the diabetic heart, is indicative of marked changes in cardiac metabolism. Conclusion:, db/db mice show impaired cardiac functional reserve capacity during maximal ,-adrenergic stimulation which is associated with unfavourable changes in cardiac energy metabolism. [source]

Maternal environment affects endogenous virus induction in the offspring of type 1 diabetes model non-obese diabetic mice

CONGENITAL ANOMALIES, Issue 3 2005
Yukiko Kagohashi
ABSTRACT Type 1 diabetes results from the destruction of pancreatic b-cells (insulitis). It is a multifactorial disease involving genetic and environmental factors, including the maternal environment. Viruses have also been implicated in the pathogenesis of human type 1 diabetes as well as in its model non-obese diabetic (NOD) mice during the perinatal period, as endogenous viruses and/or as infectious agents vertically transmitted from mothers. However, the role of virus as genetic or environmental factor and its interaction with other maternal factors remain unclear. In a series of experiments, we transplanted preimplantation-stage NOD embryos into the uterus of recipient Institute of Cancer Research (ICR) mice, which are without diabetic genetic predisposition, and NOD mice, which did not exhibit overt diabetes during the experiment, and designated offspring as NOD/ICR and NOD/NOD, respectively. We previously observed that NOD/ICR offspring developed insulitis significantly earlier than NOD/NOD offspring. To assess the role of viruses in the development of insulitis, we examined the appearance of viral particles and expression of retroviruses between NOD/ICR and NOD/NOD. NOD/ICR showed earlier expression of env region of the xenotropic type C retrovirus by polymerase chain reaction analysis than NOD/NOD, while the retrovirus-like particles were observed in the islet b-cells similarly in both groups by electron microscopy. Serum corticosterone level, which is suggested to enhance retroviral induction, was significantly higher in the ICR than in the NOD surrogate mothers. These findings suggest that the observed virus is endogenous and that maternal environmental factors, including hormone levels, affect the induction of endogenous viruses and cause the earlier onset of insulitis. [source]

Effect of reduced total blood volume on left ventricular volumes and kinetics in type 2 diabetes

ACTA PHYSIOLOGICA, Issue 1 2010
S. Lalande
Abstract Aim:, Although impaired left ventricular (LV) diastolic function is commonly observed in patients with type 2 diabetes, it remains unclear whether the impairment is caused by altered LV relaxation or changes in LV preload. The purpose of this study was to examine the influence of LV function and LV loading conditions on stroke volume in men with type 2 diabetes. Methods:, Cardiac magnetic resonance imaging scans were performed in eight men with type 2 diabetes and 11 non-diabetic men matched for age, weight and physical activity level. Total blood volume was determined with the Evans blue dye dilution technique. Results:, End-diastolic volume (EDV), the ratio of peak early to late mitral inflow velocity (E/A) and stroke volume were lower in men with type 2 diabetes than in non-diabetic individuals. Peak filling rate and peak ejection rate were not different between diabetic and non-diabetic individuals; however, men with type 2 diabetes had proportionally longer systolic duration than non-diabetic individuals. Heart rate was higher and total blood volume was lower in men with type 2 diabetes. The lower total blood volume was correlated with a lower EDV in men with type 2 diabetes. Conclusions:, Men with type 2 diabetes have an altered cardiac cycle and lower end-diastolic and stroke volume. A lower total blood volume and higher heart rate in men with type 2 diabetes suggest that changes in LV preload, independent of changes in LV relaxation or contractility, influence LV diastolic filling and stroke volume in this population. [source]

The potential of cinnamon to reduce blood glucose levels in patients with type 2 diabetes and insulin resistance

DIABETES OBESITY & METABOLISM, Issue 12 2009
S. Kirkham
Aim: Cinnamon has a long history as an antidiabetic spice, but trials involving cinnamon supplementation have produced contrasting results. The aim of this review was to examine the results of randomized controlled clinical trials of cinnamon and evaluate the therapeutic potential amongst patients with diabetes and insulin-resistant patients, particularly the ability to reduce blood glucose levels and inhibit protein glycation. Methods: A systematic electronic literature search using the medical subject headings ,cinnamon' and ,blood glucose' was carried out to include randomized, placebo-controlled in vivo clinical trials using Cinnamomum verum or Cinnamomum cassia conducted between January 2003 and July 2008. Results: Five type 2 diabetic and three non-diabetic studies (total N = 311) were eligible. Two of the diabetic studies illustrated significant fasting blood glucose (FBG) reductions of 18,29% and 10.3% (p < 0.05), supported by one non-diabetic trial reporting an 8.4% FBG reduction (p < 0.01) vs. placebo, and another illustrating significant reductions in glucose response using oral glucose tolerance tests (p < 0.05). Three diabetic studies reported no significant results. Conclusions: Whilst definitive conclusions cannot be drawn regarding the use of cinnamon as an antidiabetic therapy, it does possess antihyperglycaemic properties and potential to reduce postprandial blood glucose levels. Further research is required to confirm a possible correlation between baseline FBG and blood glucose reduction and to assess the potential to reduce pathogenic diabetic complications with cinnamon supplementation. [source]

Rediscovering bile acid sequestrants

DIABETES OBESITY & METABOLISM, Issue 12 2009
D. S. H. Bell
Aim: In the recently published The Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) mega-trial, rosuvastatin significantly reduced cardiovascular events at the expense of a small but significant increase in the risk of developing type 2 diabetes. The increased risk of new-onset diabetes was in keeping with a recent meta-analysis which suggested that statins, with the possible exception of pravastatin, marginally increase the risk of developing type 2 diabetes. Methods: Although the net effect of rosuvastatin was obviously very positive, we hypothesized that the addition of a bile aid sequestrant to a statin would not only further decrease lipid levels and potentially further decrease cardiovascular events but also protect against the development of diabetes. This is particularly relevant because the bile acid sequestrant, colesevelam, has recently been approved for therapy of diabetes. Results: Colesevelam like other bile acid sequestrants lowers low-density lipoprotein levels by 16% and C-reactive protein by 22% beyond the reductions that occur with statin therapy alone. Bile acid sequestrants confer lipid-lowering, glucose-lowering, and anti-inflammatory benefits, and have been shown to reduce risk of cardiovascular events. Conclusions: Therefore, colesevelam should be the most effective and logical agent to add to a statin in the diabetic and insulin-resistant patient, because in addition to lowering cardiac risk it may prevent the development of diabetes, as well as improving glycaemic control in the established diabetic patient. [source]

DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose tissue

DIABETES OBESITY & METABOLISM, Issue 4 2009
K. Kos
Context:, Dipeptidyl peptidase IV (DPP-IV) inactivates the incretin hormone glucagon-like peptide. It can also affect the orexigenic hormone neuropeptide Y (NPY1,36) which is truncated by DPP-IV to NPY3,36, as a consequence NPY's affinity changes from receptor Y1, which mediates the antilipolytic function of NPY, to other NPY receptors. Little is known whether DPP-IV inhibitors for the treatment of type 2 diabetic (T2DM) patients could influence these pathways. Aims:, To investigate the in vitro effects of NPY with DPP-IV inhibition in isolated abdominal subcutaneous (AbdSc) adipocytes on fat metabolism, and assessment of NPY receptor and DPP-IV expression in adipose tissue (AT). Methods:,Ex vivo human AT was taken from women undergoing elective surgery (body mass index: 27.5 (mean ± s.d.) ± 5 kg/m2, age: 43.7 ± 10 years, n = 36). Isolated AbdSc adipocytes were treated with human recombinant (rh)NPY (1,100 nM) with and without DPP-IV inhibitor (1 M); glycerol release and tissue distribution of DPP-IV, Y1 and Y5 messenger RNA (mRNA) were measured and compared between lean and obese subjects. Results and conclusion:, rhNPY reduced glycerol release, an effect that was further enhanced by co-incubation with a DPP-IV inhibitor [control: 224 (mean ± s.e.) ± 37 ,mol/l; NPY, 100 nM: 161 ± 27 ,mol/l**; NPY 100 nM/DPP-IV inhibitor, 1 M: 127 ± 14 ,mol/l**; **p < 0.01, n = 14]. DPP-IV was expressed in AbdSc AT and omental AT with relative DPP-IV mRNA expression lower in AbdSc AT taken from obese [77 ± 6 signal units (SU)] vs. lean subjects (186 ± 29 SU*, n = 10). Y1 was predominantly expressed in fat and present in all fat depots but higher in obese subjects, particularly the AbdSc AT-depot (obese: 1944 ± 111 SU vs. lean: 711 ± 112 SU**, n = 10). NPY appears to be regulated by AT-derived DPP-IV. DPP-IV inhibitors augment the antilipolytic effect of NPY in AT. Further studies are required to show whether this explains the lack of weight loss in T2DM patients treated with DPP-IV inhibitors. [source]

The effects of lipid-lowering drug therapy on cardiovascular responsiveness in type 2 diabetic patients

DIABETES OBESITY & METABOLISM, Issue 1 2006
Laurence Guy HowesArticle first published online: 18 MAR 200
Type 2 diabetes is associated with a high prevalence of dyslipidaemia and a high incidence of cardiovascular disease. Lipid lowering therapy with HMG Co-A reductase inhibitors (statins) reduce the risk of cardiovascular events in type 2 diabetic and non-diabetic patients, effects which are believed to be partly due to improvements in vascular function. The aetiology of abnormal vascular function in type 2 diabetics is likely to be multifactorial and the pattern of vascular dysfunction in type 2 diabetes may differ from that which occurs in non-diabetic patients with dyslipidaemia. Abnormalities in endothelium derived hyperpolarising factor (EDHF) mediated vasodilation in resistance vessels may be more prominent in both type 1 and type 2 diabetes than in non-diabetic patients with endothelial dysfunction. The effects of lipid lowering therapy on vascular responsiveness may differ in type 2 diabetic patients from those found in non-diabetic patients. Statin therapy does not appear to improve responses to endothelial dependent vasodilators in type 2 diabetics, but may alter the ratio between nitric oxide (NO) and EDHF mediated responses. Fibrate therapy improves flow mediated dilation of brachial arteries in type 2 diabetic patients, but only appears to improve endothelium dependant vasodilator responses in resistance vessels when given in conjunction with co-enzyme Q. [source]

Effects of short-term metformin treatment on insulin sensitivity of blood glucose and free fatty acids

DIABETES OBESITY & METABOLISM, Issue 1 2004
S. Iannello
Aim:, Based on the known effect of metformin (MET) in improving insulin sensitivity in type 2 diabetes, with the scope to focus the effects on glycaemic and free fatty acids (FFA) levels, we studied the effects of a short-term treatment with this drug in obese subjects and obese patients with diabetes or family history of diabetes (FHD). We used a method to allow us to evaluate the possible difference of insulin sensibility with regard to the insulin action on glycaemia and blood FFA, both in the basal state and during oral glucose tolerance test (OGTT). Methods:, Insulin sensitivity was investigated before and after MET treatment (850 mg bid for 10 days) in seven obese subjects with normal glucose tolerance and without FHD and 13 obese patients with diabetes (n = 7) or FHD (n = 6). By using specifically designed formulae, we calculated four insulin-sensitivity indices (ISI) from basal level (b) and area values (a) (during OGTT) of insulinaemia, glycaemia (gly) or FFA (ffa), namely: ISI (gly)-b, ISI (gly)-a, ISI (ffa)-b and ISI (ffa)-a. Results:, In patients with diabetes or FHD, MET improved ISI (gly)-b (0.79 ± 0.06 vs. 0.59 ± 0.07, p < 0.001) and ISI (gly)-a (0.69 ± 0.09 vs. 0.51 ± 0.07, p < 0.05), whereas only minor changes occurred for ISI (ffa)-b and ISI (ffa)-a. In contrast, in simple obese subjects, MET induced further deterioration of both ISI (gly)-a (0.47 ± 0.07 vs. 0.64 ± 0.10, p < 0.01) and ISI (ffa)-a (0.43 ± 0.07 vs. 0.55 ± 0.08, p < 0.05). Fasting level and total area of lactate were high in the obese patients and were not affected by MET. A statistically significant increase (p < 0.01), however, was observed for the ,decremental' area of lactate in obese subjects with diabetes or FHD, which might probably contribute to the reduction of insulin resistance induced by the drug in these patients. Conclusions:, Although the low number of subjects studied precludes absolute conclusions, data would suggest that MET improved ISI towards glucose but not towards FFA, in the diabetic and ,prediabetic' obese patients, whereas worsened it in the obese subjects without FHD. Therefore, the effects of MET would not be secondary to changes of FFA but rather to a primary action of MET on glucose metabolism. Thus, utilization of MET to treat the insulin resistance in obesity is indicated only in the presence of alterations of glucose metabolism or FHD. [source]

Relationship of glucose regulation to changes in weight: a systematic review and guide to future research

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2010
Ching-Ju Chiu
Abstract Although weight gain and obesity are risk factors for poor glucose regulation, the relationship, if any, of glucose regulation to changes in weight is not well understood. The purpose of this study was to conduct a systematic review of research examining the relationship of glucose regulation to changes in weight in human-based studies and to provide guidelines for future research in this area. We searched electronic databases and reference sections of relevant articles, including both diabetic and non-diabetic populations, to locate all the literature published before February 2010, and then conducted a systematic review across studies to compare the research designs and findings. The 22 studies meeting our criteria for review generally supported the relationship of glucose regulation to changes in weight. Three studies reported that poor glucose regulation is associated with weight gain; 12 studies concluded that poor glucose regulation is associated with weight loss; 5 showed complex relationships depending on age, sex, or race/ethnicity; and 2 suggested no relationship. The diverse findings may imply that the direction (negative or positive) of the relationship may depend on specific conditions. More research focused on different subpopulations may provide more definitive information supplemental to the current preliminary findings. Recommendations regarding future research in this particular area are provided in the discussion. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Coxsackievirus B4 and type 1 diabetes pathogenesis: contribution of animal models

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2009
H. Jaïdane
Abstract The role of enteroviruses, in particular type B coxsackieviruses (CV-B), in type 1 diabetes (T1D) pathogenesis is supported by epidemiological, clinical and experimental observations. The investigation of T1D pathogenesis benefits from the contribution of animal models called spontaneously diabetic. Among these animals the non-obese diabetic (NOD) mouse and the bio-breeding diabetes-prone (BBDP) rat present a genetic susceptibility manifested by the expression of an autoimmune diabetes similar to the pathology observed in human beings. Other models whose genetic predisposition is less known are of considerable contribution as well. Numerous major observations relative to several aspects of T1D pathogenesis in the context of CV-B infections, such as susceptibility, diabetogenicity, pancreatotropism, mechanisms of , cells destruction and others, have been deduced thanks to investigations with animal models. Despite their limits, these models are necessary in improving our knowledge of the role of enteroviruses, like CV-B4, in the pathogenesis of T1D, and the recent advances ensuing from their contribution may have important therapeutic and preventive spin-offs. Copyright © 2009 John Wiley & Sons, Ltd. [source]

,-Lipoic acid reduces congenital malformations in the offspring of diabetic mice

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2009
Y. Sugimura
Abstract Background The mechanism of diabetes-induced congenital malformation remains to be elucidated. It has been reported that ,-lipoic acid (LA) prevents neural tube defects (NTDs) in offsprings of rats with streptozotocin-induced diabetes. Here, we evaluate the protective effect of LA against diabetic embryopathy, including NTDs, cardiovascular malformations (CVMs), and skeletal malformations, in mice. Methods Female mice were rendered hyperglycemic using streptozotocin and then mated with normal male mouse. Pregnant diabetic or non-diabetic mice were treated daily with either LA (100 mg/kg body weight) or saline between gestational days 0 and 18. On day 18, fetuses were examined for congenital malformations. Results Plasma glucose levels on day 18 were not affected by LA treatment. No congenital malformations were observed either in the saline-treated or LA-treated non-diabetic group. In the saline-treated diabetic group, 39% of fetuses had external malformations and 30% had NTDs. In the LA-treated diabetic group, the corresponding proportions were 11 and 8%, respectively. LA treatment also decreased the incidence of CVMs from 30,3% and of skeletal malformations from 29,6%. Conclusions We conclude that LA can reduce NTDs, CVMs and skeletal malformations in the offspring of diabetic mice at term delivery. Copyright © 2009 John Wiley & Sons, Ltd. [source]

C-peptide constricts pancreatic islet arterioles in diabetic, but not normoglycaemic mice

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2008
Lina Nordquist
Abstract Background Pancreatic islet blood flow is regulated separately from that of the exocrine pancreas, and a consistent finding during impaired glucose tolerance is an increased blood perfusion. The aim of the present study was to investigate whether C-peptide affects pancreatic islet arterioles in normal and diabetic mice. Materials and Methods Control and diabetic C57-Bl mice were studied after 2 weeks of alloxan-induced diabetes. Islet arterioles were dissected and microperfused with Dulbecco's modified Eagle medium (DMEM) solution. The effect of luminal application of mouse C-peptide was investigated. Results C-peptide reduced the diameter of islet arterioles from diabetic mice (,10 ± 4%, P < 0.05) compared to base-line values, whilst arterioles from normoglycaemic animals did not respond to C-peptide (P = 0.2). Conclusion These findings suggest a role for C-peptide in the regulation of islet blood flow, especially during conditions with impaired glucose tolerance. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Viral infections as potential triggers of type 1 diabetes

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2007
Nienke van der Werf
Abstract During the last decades, the incidence of type 1 diabetes (T1D) has increased significantly, reaching percentages of 3% annually worldwide. This increase suggests that besides genetical factors environmental perturbations (including viral infections) are also involved in the pathogenesis of T1D. T1D has been associated with viral infections including enteroviruses, rubella, mumps, rotavirus, parvovirus and cytomegalovirus (CMV). Although correlations between clinical presentation with T1D and the occurrence of a viral infection that precedes the development of overt disease have been recognized, causalities between viruses and the diabetogenic process are still elusive and difficult to prove in humans. The use of experimental animal models is therefore indispensable, and indeed more insight in the mechanism by which viruses can modulate diabetogenesis has been provided by studies in rodent models for T1D such as the biobreeding (BB) rat, nonobese diabetic (NOD) mouse or specific transgenic mouse strains. Data from experimental animals as well as in vitro studies indicate that various viruses are clearly able to modulate the development of T1D via different mechanisms, including direct ,-cell lysis, bystander activation of autoreactive T cells, loss of regulatory T cells and molecular mimicry. Data obtained in rodents and in vitro systems have improved our insight in the possible role of viral infections in the pathogenesis of human T1D. Future studies will hopefully reveal which human viruses are causally involved in the induction of T1D and this knowledge may provide directions on how to deal with viral infections in diabetes-susceptible individuals in order to delay or even prevent the diabetogenic process. Copyright © 2007 John Wiley & Sons, Ltd. [source]

The role of taurine in diabetes and the development of diabetic complications

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2001
Svend Høime Hansen
Abstract The ubiquitously found ,-amino acid taurine has several physiological functions, e.g. in bile acid formation, as an osmolyte by cell volume regulation, in the heart, in the retina, in the formation of N -chlorotaurine by reaction with hypochlorous acid in leucocytes, and possibly for intracellular scavenging of carbonyl groups. Some animals, such as the cat and the C57BL/6 mouse, have disturbances in taurine homeostasis. The C57BL/6 mouse strain is widely used in diabetic and atherosclerotic animal models. In diabetes, the high extracellular levels of glucose disturb the cellular osmoregulation and sorbitol is formed intracellularly due to the intracellular polyol pathway, which is suspected to be one of the key processes in the development of diabetic late complications and associated cellular dysfunctions. Intracellular accumulation of sorbitol is most likely to cause depletion of other intracellular compounds including osmolytes such as myo -inositol and taurine. When considering the clinical complications in diabetes, several links can be established between altered taurine metabolism and the development of cellular dysfunctions in diabetes which cause the clinical complications observed in diabetes, e.g. retinopathy, neuropathy, nephropathy, cardiomyopathy, platelet aggregation, endothelial dysfunction and atherosclerosis. Possible therapeutic perspectives could be a supplementation with taurine and other osmolytes and low-molecular compounds, perhaps in a combinational therapy with aldose reductase inhibitors. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Parallel increase of plasma apoproteins C-II and C-III in Type 2 diabetic patients

DIABETIC MEDICINE, Issue 7 2009
S. Béliard
Abstract Aims, To determine plasma levels of apoprotein (apo) C-II and apoprotein C-III in Type 2 diabetic patients and to examine the clinical and biological factors that are associated with elevated apoC concentrations. Methods, We measured apoC-II and apoC-III in total plasma and in non-high-density lipoprotein fractions by an immunoturbidimetric assay in 88 Caucasian Type 2 diabetic patients and in 138 healthy control subjects. Results, Plasma levels of both apoC-II and apoC-III were increased in Type 2 diabetic patients. The clinical conditions associated with an increase of plasma apoC-II and apoC-III were abdominal obesity, body mass index, poor glycaemic control and lack of insulin treatment. However, when multivariate analysis was used, plasma apoCs levels correlated with triglyceride levels only. The apoC-III/apoC-II ratio was similar in the Type 2 diabetic and control subjects. Conclusions, Our study shows the parallel increase of apoC-II and C-III in Type 2 diabetic patients. This parallel increase is related to hypertriglyceridaemia only. [source]

Are symptoms of depression more common in diabetes?

DIABETIC MEDICINE, Issue 11 2008
Results from the Heinz Nixdorf Recall study
Abstract Aims To estimate the association between depressive symptoms and Type 2 diabetes, as well as previously undetected diabetes, in a large population-based sample in Germany and to determine associated variables. Methods We used baseline data on 4595 participants (age 45,75 years, 50.2% women) from the German Heinz Nixdorf Recall study, a population-based, prospective cohort study which started in 2000. Diabetes mellitus was assessed by self report (physician diagnosis or medication), undiagnosed diabetes based on blood glucose levels. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale short form (cut-off , 15 points). We fitted multiple logistic regression models. Results The prevalence of diagnosed and previously undetected diabetes was 9.3% (95% confidence interval 8.2,11.6) and 7.6% (6.6,8.8) in men and 6.0% (5.1,7.1) and 3.2% (2.5,4.0) in women, respectively. Compared with non-diabetic women, the prevalence of depressive symptoms was not significantly different in diabetic women (age-adjusted odds ratio, 95% confidence interval 1.48; 0.98,2.24) and women with undiagnosed diabetes (0.67; 0.33,1.36). In men, the prevalence of depressive symptoms tended to be lower in diabetic than in non-diabetic subjects (0.62; 0.35,1.09), but the depressive symptoms were significantly less frequent in men with undiagnosed diabetes (0.30; 0.13,0.70). The pattern remained after further adjustment. Significant associations with depressive symptoms were found for co-morbidities and living without a partner in both women and in men, and for body mass index and activity level in women only. Conclusions After adjustment for relevant covariates, the association between depressive symptoms and Type 2 diabetes was heterogenous in our population-based study. In subjects with undiagnosed diabetes, however, depressive symptoms were less frequent in men. Co-morbidities and psychosocial conditions are strongly associated with depressive symptoms. [source]

Plasma triglycerides and LDL cholesterol are related in a parabolic fashion in the general population and patients with Type 2 diabetes mellitus: long-term follow-up results from the Hoorn study

DIABETIC MEDICINE, Issue 9 2008
M. C. G. J. Brouwers
Abstract Aims Low-density lipoprotein cholesterol (LDL-C) levels are often fairly normal in Type 2 diabetes mellitus (DM). We anticipated that a parabolic relation between plasma triglycerides and LDL-C, as previously demonstrated in familial combined hyperlipidaemia (FCHL), might account for this phenomenon. Methods Our hypothesis was tested in 1343 subjects derived from the general population who were studied on two occasions 6 years apart (the Hoorn study). Three groups were constructed depending on plasma triglycerides: group A (individuals with both measurements below 1.5 mmol/l), group B (one measurement below and one above 1.5 mmol/l) and group C (both measurements above 1.5 mmol/l). Diabetes status was ascertained by an oral glucose tolerance test. Results In a mixed linear model, a significant, positive relation between triglycerides and LDL-C was observed for males in group A (,a = 0.5, P < 0.001) and group B (,b = 0.2, P < 0.001), whereas a significant negative relation was found for males in group C (,c = ,0.2, P = 0.003). The regression slopes did not differ between diabetic and non-diabetic subjects. Similar results were obtained for women, with the exception that the relation was not significantly negative in group C (,c = ,0.1, P = 0.4). Conclusion Plasma triglcyerides and LDL-C are related in a parabolic fashion, not only in FCHL, but also in the general population and Type 2 DM. These findings aid our interpretation of typical dyslipidaemia and the effects of treatment that are frequently observed in hypertriglyceridaemic states. [source]

Interaction of the G182C polymorphism in the APOA5 gene and fasting plasma glucose on plasma triglycerides in Type 2 diabetic subjects

DIABETIC MEDICINE, Issue 12 2005
Y.-D. Jiang
Abstract Aim Apolipoprotein AV (APOA5) is an important determinant of plasma triglyceride concentration. This study aimed to investigate the relationship of an amino acid substitution at position 182 (G182C) of the apolipoprotein AV (APOA5) gene with triglyceride concentration in a Taiwanese population. Methods This study enrolled two cohorts: non-diabetic subjects (112 males and 89 females) aged 50.3 ± 11.0 years (mean ± sd) and diabetic subjects (106 males and 96 females) aged 62.1 ± 10.3 years. The relationship between the G182C polymorphism (rs 2075291) and plasma triglycerides was examined. Demographic and metabolic parameters including age, sex, body mass index, fasting plasma glucose and total cholesterol were also obtained. Results The G182C polymorphism was a determinant of plasma triglycerides in both non-diabetic (P = 0.022) and diabetic (P = 0.003) groups, independent of age, gender, fasting plasma glucose, body mass index and total cholesterol. In the diabetic group, this genetic polymorphism interacts significantly (P = 0.032) with fasting plasma glucose concentration on plasma triglycerides after adjustment for age, sex, body mass index and total cholesterol. Conclusions In conclusion, the G182C polymorphism of the APOA5 gene affects plasma triglycerides in both non-diabetic and diabetic populations. The observed interaction of gene and glycaemic control further indicates a multifactorial nature of clinical phenotypes in subjects with Type 2 diabetes. Diabet. Med. (2005) [source]

Peroxisome proliferator-activated receptor-, co-activator-1, (PGC-1,) gene polymorphisms and their relationship to Type 2 diabetes in Asian Indians

DIABETIC MEDICINE, Issue 11 2005
K. S. Vimaleswaran
Abstract Aims The objective of the present investigation was to examine the relationship of three polymorphisms, Thr394Thr, Gly482Ser and +A2962G, of the peroxisome proliferator activated receptor-, co-activator-1 alpha (PGC-1,) gene with Type 2 diabetes in Asian Indians. Methods The study group comprised 515 Type 2 diabetic and 882 normal glucose tolerant subjects chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The three polymorphisms were genotyped using polymerase chain reaction,restriction fragment length polymorphism (PCR,RFLP). Haplotype frequencies were estimated using an expectation,maximization (EM) algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. Results The three polymorphisms studied were not in linkage disequilibrium. With respect to the Thr394Thr polymorphism, 20% of the Type 2 diabetic patients (103/515) had the GA genotype compared with 12% of the normal glucose tolerance (NGT) subjects (108/882) (P = 0.0004). The frequency of the A allele was also higher in Type 2 diabetic subjects (0.11) compared with NGT subjects (0.07) (P = 0.002). Regression analysis revealed the odds ratio for Type 2 diabetes for the susceptible genotype (XA) to be 1.683 (95% confidence intervals: 1.264,2.241, P = 0.0004). Age adjusted glycated haemoglobin (P = 0.003), serum cholesterol (P = 0.001) and low-density lipoprotein (LDL) cholesterol (P = 0.001) levels and systolic blood pressure (P = 0.001) were higher in the NGT subjects with the XA genotype compared with GG genotype. There were no differences in genotype or allelic distribution between the Type 2 diabetic and NGT subjects with respect to the Gly482Ser and +A2962G polymorphisms. Conclusions The A allele of Thr394Thr (G , A) polymorphism of the PGC-1 gene is associated with Type 2 diabetes in Asian Indian subjects and the XA genotype confers 1.6 times higher risk for Type 2 diabetes compared with the GG genotype in this population. [source]

Association of aldose reductase gene Z+2 polymorphism with reduced susceptibility to diabetic nephropathy in Caucasian Type 1 diabetic patients

DIABETIC MEDICINE, Issue 8 2004
M. Lajer
Abstract Aims The Z,2 allele of the (AC)n polymorphism in the aldose reductase gene (ALR2) confers increased risk of microvascular diabetic complications, whereas the Z+2 allele has been proposed to be a marker of protection. However data are conflicting. Therefore, we investigated whether this polymorphism is associated with diabetic nephropathy and retinopathy in Type 1 diabetes mellitus in a large case,control study and a family-based analysis. Methods A total of 431 Type 1 diabetic patients with diabetic nephropathy and 468 patients with longstanding Type 1 diabetes and persistent normoalbuminuria were genotyped for the case,control study. In addition, 102 case trios and 98 control trios were genotyped for a family-based study. Results Thirteen different alleles were identified. In the case,control study, the Z+2 allele frequency was significantly higher in the normoalbuminuric diabetic than in patients with diabetic nephropathy (0.17 vs. 0.11, P = 0.008), suggesting a protective function of the Z+2 allele. No significant increase in the frequency of the putative risk allele Z,2 was found in patients with diabetic nephropathy vs. controls (0.39 vs. 0.36). No association with diabetic retinopathy was found. Although the results of the transmission of the Z,2 and Z+2 alleles in the independent family-based study were consistent with the association study, the number of informative families was limited and thus differences were not statistically significant. Conclusions The Z+2 allele of the ALR2 promoter polymorphism is associated with a reduced susceptibility to diabetic nephropathy in Danish Type 1 diabetic patients, suggesting a minor role for the polyol pathway in the pathogenesis of diabetic kidney disease. No association of the ALR2 polymorphism with diabetic retinopathy was found. [source]

Hospital outcome of acute myocardial infarction in patients with and without diabetes mellitus

DIABETIC MEDICINE, Issue 2 2004
W. Otter
Abstract Aims To assess hospital mortality and morbidity in diabetic and non-diabetic patients with acute myocardial infarction and to compare the results between the two groups. Methods All patients admitted in 1999 to the intensive care unit of the Schwabing City Hospital with diagnosis of acute myocardial infarction were assessed for hospital mortality and co-morbidity. Results Three hundred and thirty patients with acute myocardial infarction were admitted. Of those, 126 (38%) were diabetic and 204 (62%) were non-diabetic patients. Mortality within 24 h after admission was 13.5% in diabetic patients and 5.4% in non-diabetic patients (P < 0.01). Mortality during entire hospitalization was higher in diabetic than in non-diabetic patients (29.4% vs. 16.2%; P = 0.004). Diabetic patients were resuscitated more frequently than non-diabetic patients (24% vs. 11%, P < 0.01). In diabetic patients, heart rate at admission was increased (91 ± 27 vs. 82 ± 23/min; P < 0.01) and presence of angina pectoris was reported less frequently (59% (n = 72) vs. 82% (n = 167); P < 0.001). Preceding myocardial infarction, microalbuminuria, peripheral artery disease and arterial hypertension were more frequent in diabetic than in non-diabetic patients. Diabetic patients demonstrated higher C-reactive protein (CRP) levels than non-diabetic patients (91.4 ± 78.2 mg/l vs. 45.2 ± 62.4 mg/l; P < 0.001). Conclusions In diabetic patients with acute myocardial infarction, early hospital mortality is increased and signs of cardiac autonomic dysfunction and microangiopathy are detected more frequently than in non-diabetic patients. The need for advanced treatment strategies early in the course of diabetic patients with myocardial infarction is emphasized. Diabet. Med. 21, 183,187 (2004) [source]

How should peripheral neuropathy be assessed in people with diabetes in primary care?

DIABETIC MEDICINE, Issue 5 2003
A population-based comparison of four measures
Abstract Aims To test the accuracy of four measures of peripheral diabetic neuropathy in a primary care population. Methods Type 2 diabetic (n = 544) and 544 non-diabetic participants aged 45,76 years were randomly selected from general practice registers. Neuropathy was assessed using vibration threshold (VT) and scores for light touch, thermal sense and modified Michigan Neuropathy Screening Instrument questionnaire. These measures were assessed for variation with diabetes status, age, diabetes duration, HbA1c, and presence of retinopathy and nephropathy. Light touch, thermal sense and questionnaire scores were assessed against VT using ROC curve analysis. Results Only VT and light touch were different between diabetic and non-diabetic groups (P = 0.02 and < 0.0001, respectively). All measures were significantly associated with diabetes duration and retinopathy, and all except questionnaire score (P = 0.14) with age. None was associated with nephropathy and only questionnaire score was associated with HbA1c (P = 0.033). VT varied as expected across scores of light touch (,2 = 41.65, P = 0.0001), thermal sense (,2 = 15.86, P = 0.015) and questionnaire (,2 = 21.22, P = 0.047). Area under the curve values for light touch, thermal and questionnaire scores were 0.72 (95% confidence interval (CI) 0.63, 0.82), 0.63 (95% CI 0.52, 0.73) and 0.64 (95% CI 0.53, 0.74), respectively. Conclusions All measures had associations with risk factors for neuropathy, but light touch score (monofilament) had the strongest association with vibration threshold (the chosen gold standard) and thus appeared the most appropriate tool for use in primary care, because of its validity and simplicity of use. Diabet. Med. 20, 368,374 (2003) [source]

The Houssay phenomenon, another clue to Sheehan's syndrome in a diabetic

DIABETIC MEDICINE, Issue 9 2002
M. Hadithi
No abstract is available for this article. [source]

Transforming growth factor-beta 1, 2, 3 and receptor type I and II in diabetic foot ulcers

DIABETIC MEDICINE, Issue 6 2002
E. B. Jude
Abstract Aims To study the distribution of transforming growth factor-beta (TGF-,) 1, 2 and 3, and TGF-, receptor types I and II in diabetic foot ulcers, diabetic skin and normal skin by immunohistochemistry, immunofluorescence and Western blotting. We also compared the TGF-,s with those of chronic venous ulcers. Methods Skin biopsies were obtained from the leg or the foot of non-diabetic and diabetic subjects, and from the edge of diabetic foot ulcers and chronic venous ulcers. Distribution (by immunofluorescence and immunocytochemistry) of TGF-, 1, 2 and 3 and TGF-, receptors (RI and RII) was done by staining 8-µm skin sections using appropriate antibodies. Protein levels of TGF-, were measured by Western blot analysis. Results TGF-,3 expression was increased in the epithelium at the edge of diabetic foot ulcers, being more intense than diabetic and normal skin (P = 0.03, 0.02, respectively), as was its expression in venous ulcers compared with normal skin. However, TGF-,1 expression was not increased in diabetic foot ulcers and chronic venous ulcers, and was comparable to diabetic and normal skin. There was also no increase for the receptors in diabetic foot ulcers. Conclusion The lack of TGF-,1 up-regulation in both diabetic foot ulcers and venous ulcers may explain the impaired healing in these chronic wounds, and could represent a general pattern for chronicity. [source]