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Signalling mechanisms linking hepatic glucose and lipid metabolism.
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Weickert MO, Pfeiffer AF
Fatty liver and hepatic triglyceride accumulation are strongly associated with obesity, insulin resistance and type 2 diabetes, and are subject to nutritional influences. Hepatic regulation of glucose and lipid homeostasis is influenced by a complex system of hormones, hormonally regulated signalling pathways and transcription factors. Recently, considerable progress has been made in elucidating molecular pathways and potential factors that are affected in insulin-resistant states. In this review we discuss some of the key factors that are involved in both the regulation of glucose and lipid metabolism in the liver. Understanding the molecular network that links hepatic lipid accumulation and impaired glucose metabolism may provide targets for dietary or pharmacological interventions.
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Understanding of diabetes prevention studies: questionnaire survey of professionals in diabetes care.
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, Mühlhauser I, Kasper J, Meyer G
AIMS/HYPOTHESIS: Diabetes prevention studies have reported reductions of diabetes risk by up to 60%. Since the underlying metabolic changes are small, the clinical significance of this effect may be overestimated. The present survey explores the extent to which different formats of presenting study results may influence diabetes healthcare professionals' perceptions of the importance of intervention effects on diabetes risk. SUBJECTS, MATERIALS AND METHODS: Participants of three European diabetes conferences (160 nurse educators, 112 physicians, 27 other professionals) were presented with a questionnaire that included nine items, in which results from three diabetes prevention studies were presented in different ways. RESULTS: Participation rate was 96%. Effects were interpreted as important or very important by 92% (255/276) when results were presented as proportions of subjects with diabetes (14% intervention group, 29% control group), by 87% (248/285) when results were communicated as a risk reduction of 57%, by 39% (110/284) when the corresponding fasting plasma glucose values were presented (mean difference 0.3 mmol/l), and by 18% (52/283) when glycosylated haemoglobin values were used (6.0 vs 6.1%). Corresponding results of the three diabetes prevention studies were rated as being of identical importance by only 23, 13 and 16% of participants, respectively. CONCLUSIONS AND INTERPRETATION: Healthcare professionals rate the benefit of preventive interventions substantially higher when changes in diabetes risk are communicated rather than related glycaemic parameters. Transformation of continuous metabolic data into diagnostic categories may impair understanding of study effects.
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Global gene expression analysis in liver of obese diabetic db/db mice treated with metformin.
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Heishi M, Ichihara J, Teramoto R, Itakura Y, Hayashi K, Ishikawa H, Gomi H, Sakai J, Kanaoka M, Taiji M, Kimura T
AIMS/HYPOTHESIS: Metformin is widely used as a hypoglycaemic reagent for type 2 diabetes. While the reduction of hepatic gluconeogenesis is thought to be a key effect, the detailed molecular mechanism of action of metformin remains to be elucidated. To gain insight into this, we performed a global gene expression profiling study. MATERIALS AND METHODS: We performed DNA microarray analysis to study global gene expression in the livers of obese diabetic db/db mice 2 h after a single administration of metformin (400 mg/kg). RESULTS: This analysis identified 14 genes that showed at least a 1.5-fold difference in expression following metformin treatment, including a reduction of glucose-6-phosphatase gene expression. The mRNA levels of glucose-6-phosphatase showed one of the best correlations with blood glucose levels among 12,000 genes. Enzymatic activity of glucose-6-phosphatase was also reduced in metformin-treated liver. Moreover, intensive analysis of the expression profile revealed that metformin effected significant alterations in gene expression across at least ten metabolic pathways, including those involved in glycolysis-gluconeogenesis, fatty acid metabolism and amino acid metabolism. CONCLUSIONS/INTERPRETATION: These results suggest that reduction of glucose-6-phosphatase activity, as well as suppression of mRNA expression levels of this gene, in liver is of prime importance for controlling blood glucose levels in vivo, at least at early time points after metformin treatment. Our results also suggest that metformin not only affects expression of specific genes, but also alters the expression level of multiple genes linked to the metabolic pathways involved in glucose and lipid metabolism in the liver.
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Current and former smoking increases mortality in patients on peritoneal dialysis.
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Braatvedt GD, Rosie B, Bagg W, Collins J
AIMS: There is limited information on the effects of smoking behaviour on mortality in patients with end-stage renal failure (ESRF).This study aimed to assess the interaction of smoking on death rate in patients with renal failure on dialysis. METHODS: All patients (n=1293) commencing peritoneal dialysis between 1985 and 1995 for renal failure in New Zealand were prospectively followed 6 monthly until 1997 and data entered on the National database. Mortality rates were calculated from the national database and rates in patients with diabetes compared with those without diabetes and in those who did or did not smoke. RESULTS: Follow-up data was available on all patients for a range of 20-40 months. 35% of the patients were clinically classified as having diabetic nephropathy as the cause of renal failure (11% type 1, 24% type 2). Seventeen percent of the total cohort were current smokers, 45% former smokers and 38% lifetime non smokers at dialysis commencement. These rates were similar between patients with diabetes (18% current, 51% former, 32% non-smoker) and those without diabetes (17% current, 42% former, 41% non-smoker). At survey end in 1997, 43% of the patients without diabetes had died compared with 59% of patients with type 1 diabetes (p<0.05) and 62% of patients with type 2 diabetes (p<0.05). The age-adjusted mortality of patients with a history of current or former smoking was higher than non-smokers. Those patients with diabetes and a history of smoking had even higher mortality. CONCLUSIONS: Patients with a current or former history of smoking on peritoneal dialysis are at greatly increased risk of death. A strategy of aggressive smoking cessation efforts should be adopted for these patients at the earliest opportunity.
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Long-term effect of Trigonella foenum graecum and its combination with sodium orthovanadate in preventing histopathological and biochemical abnormalities in diabetic rat ocular tissues.
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Preet A, Siddiqui MR, Taha A, Badhai J, Hussain ME, Yadava PK, Baquer NZ
Trigonella foenum graecum seed powder (TSP) and Sodium Orthovanadate (SOV) have been shown to demonstrate antidiabetic effects by stabilizing glucose homeostasis and carbohydrate metabolism in experimental type-1 diabetes. However their efficacy in controlling histopathological and biochemical abnormalities in ocular tissues associated with diabetic retinopathy is not known. The purpose of this study was to investigate the comparative efficacy of individual as well as combination therapy of TSP and SOV in 8 weeks diabetic rat lens and retina. Retinas and lenses were taken from control, alloxan-induced diabetic rats and diabetic rats treated separately with insulin, 5%TSP, SOV (0.6 mg/ml) and a combined dose of SOV (0.2 mg/ml) and 5%TSP for 60 days. Control and each experimental group had six rats. Alterations in the activities of enzymes HK (hexokinase), AR (aldose reductase), SDH (sorbitol dehydrogenase), G-6-PD (glucose-6-phosphate dehydrogenase), GPx (glutathione peroxidase), GR (glutathione reductase) and levels of metabolites like sorbitol, fructose, glucose, MDA (malondialdehyde) and GSH (reduced glutathione) were measured in the cytosolic fraction of lenses besides measuring blood glucose levels and glycosylated haemoglobin. Histopathological abnormalities were studied in the lens using photomicrography and retina using transmission electron microscopy. Blood glucose, glycosylated haemoglobin levels and polyol pathway enzymes AR and SDH increased significantly causing accumulation of sorbitol and fructose in the diabetic lens and treatment with SOV and TSP significantly (p < 0.05) decreased these to control levels. Similarly, SOV and TSP treatments modulated the activities of HK, G-6-PD, GPx and GR in the rat lens to control values. Ultrastructure of the diabetic retina revealed disintegration of the inner nuclear layer cells with reduction in rough endoplasmic reticulum and swelling of mitochondria in the bipolar cells; and these histopathological events were effectively restored to control state by SOV and TSP treatments. In this study SOV and TSP effectively controlled ocular histopathological and biochemical abnormalities associated with experimental type-1 diabetes, and a combination regimen of low dose of SOV with TSP demonstrated the most significant effect. In conclusion, the potential of SOV and TSP alone or in low dose combination may be considered as promising approaches for the prevention of diabetic retinopathy and other ocular disorders.
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Detection of small-fiber neuropathy by sudomotor testing.
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Low VA, Sandroni P, Fealey RD, Low PA
The symptoms of burning sensation affecting the feet, thought to be due to a distal small-fiber neuropathy (DSFN) affecting somatic unmyelinated fibers, are usually accompanied by vasomotor or sudomotor changes suggestive of involvement of autonomic fibers. We therefore examined the relationship between pattern of anhidrosis and DSFN and its etiology, comparing patients with "pure" DSFN (with normal nerve conduction) to those with clinical DSFN (minor conduction abnormalities). We reviewed 125 cases with a clinical phenotype of DSFN. These patients had distal burning discomfort, variable sensory deficits, and intact motor function. All had undergone assessment with thermoregulatory sweat test (TST), autonomic reflex screen (ARS), and nerve conduction studies and electromyography (NCS/EMG). TST showed a distal pattern of anhidrosis in 74%. The quantitative sudomotor axon reflex test (QSART) was abnormal in 74%, with 80% of those having a length-dependent pattern of anhidrosis/hypohidrosis. In total, 93% of patients had a distal pattern of abnormality on QSART or TST. The Composite Autonomic Severity Score (CASS) was used to quantify the severity and distribution of autonomic deficits: 98% had CASS abnormality (sudomotor, 98%; adrenergic, 43%; cardiovagal, 35%). EMG was normal or showed unrelated abnormalities in 75%. The most common etiologies of DSFN were idiopathic (73%), presumed hereditary (18%), and diabetes (10%). Sudomotor examination is thus a highly sensitive detection tool in DSFN. Autonomic involvement is mainly distal, and additionally may involve adrenergic and the long cardiovagal fibers. Muscle Nerve, 2006.
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A concomitant review of the effects of diabetes mellitus and hypothyroidism in wound healing.
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Ekmektzoglou KA, Zografos GC
This paper reviews the negative impact of diabetes mellitus or hypothyroidism on wound healing, both in experimental and clinical settings. Since both are metabolic disorders of great clinical importance, special attention is given, not only to their pathophysiology, but also to their biochemical and histological effects on tissue integrity and regeneration. Also, special focus is awarded on wound healing of the gastrointestinal tract, i.e. in intestinal anastomosis, and how these disorders can lead to wound dehiscence. Since diabetes mellitus and hypothyroidism can coexist in clinical settings, more research must be directed on their influence on wound healing, considering them as one clinical entity.
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Preliminary Evidence of FABP2 A54T Polymorphism Associated with Reduced Risk of Type 2 Diabetes and Obesity in Women from a German Cohort.
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Fisher E, Li Y, Burwinkel B, Kühr V, Hoffmann K, Möhlig M, Spranger J, Pfeiffer A, Boeing H, Schrezenmeir J, Döring F
The T54 variant of the FABP2 gene has shown an association with the insulin resistance syndrome in some, but not all, studies. Here, we tested the hypothesis that the association between FABP2 A54T genotype and type 2 diabetes (T2DM) is confounded by body mass index (BMI) and is different between the two genders. 192 incident cases of T2DM and 384 sex- and age-matched controls were taken from the EPIC-Potsdam study cohort. Logistic regression analyses revealed that BMI was a strong confounder for diabetes risk association among women. When adjusted for BMI, the homozygous T54 variant was significantly associated with reduced risk of T2DM in women (OR = 0.24, 95 %CI: 0.07 - 0.82), but not in men in the co-dominant inheritance model. Accordingly, HbA (1c) values were significantly lower in women carrying two T54 alleles with BMI regarded as covariate. While accounting for potentially confounding effects, linear trends of increased BMI and leptin values were observed in women according to the presence of T54 alleles. The interaction term (p = 0.04) of continuous BMI and T54-coding genotypes suggested that the T54 variant is an effect-modifier for BMI in females. We conclude that the T54 allele of FABP2 A54T is associated both with higher BMI and reduced risk of T2DM in women from the German EPIC-Potsdam study.
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The Effect of Oral Glucose Loads on Tissue Metabolism During Angiotensin II Receptor and Beta-receptor Blockade in Obese Hypertensive Subjects.
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Boschmann M, Kreuzberg U, Engeli S, Adams F, Franke G, Klaua S, Scholze J, Weidinger G, Luft FC, Sharma AM, Jordan J
AT1 receptor blockers and ACE inhibitors decrease the risk for new onset diabetes mellitus. The phenomenon could be related to a direct angiotensin II effect on tissue metabolism. To address the issue, we recruited eighteen obese hypertensive patients. Patients were randomized to double-blind treatment with either valsartan (n = 8) or atenolol (n = 10) for thirteen weeks. They underwent an oral glucose tolerance test before and during active treatment, while metabolism was monitored through subcutaneous and intramuscular microdialysis and indirect calorimetry. After glucose ingestion, venous glucose and insulin concentrations increased rapidly while systemic free fatty acid concentrations were suppressed. Dialysate glucose and lactate concentrations increased briskly in adipose tissue and in skeletal muscle. Dialysate glycerol decreased profoundly in both tissues. Respiratory quotient increased markedly after glucose ingestion. These responses were identical at baseline and during active treatment either drug. We conclude that AT1 receptor blockade in obese hypertensive patients has no effect on interstitial glucose supply, lipolysis, and substrate oxidation. One possible explanation is that angiotensin II levels in obese hypertensives are not sufficient to elicit the metabolic changes that have been observed after direct angiotensin II application. The exact mechanism by which inhibition of the renin-angiotensin-aldosterone system decreases the diabetes risk remains unresolved and requires further study.
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Renal amino acid, fat and glucose metabolism in type 1 diabetic and non-diabetic humans: effects of acute insulin withdrawal.
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Moller N, Jensen MD, Rizza RA, Andrews JC, Nair KS
AIMS/HYPOTHESIS: The aim of this study was to test the hypothesis that type 1 diabetes alters renal amino acid, glucose and fatty acid metabolism. MATERIALS AND METHODS: We studied five C-peptide-negative, type 1 diabetic subjects during insulin replacement (glucose 5.6 mmol/l) and insulin deprivation (glucose 15.5 mmol/l) and compared them with six non-diabetic subjects. Leucine, phenylalanine, tyrosine, glucose and palmitate tracers were infused after an overnight fast and samples were obtained from the renal vein, femoral vein and femoral artery. RESULTS: Insulin deprivation significantly increased whole-body fluxes (20-25%) of phenylalanine, tyrosine and leucine, and leucine oxidation (50%). Kidney contributed 5-10% to the whole-body leucine and phenylalanine flux. A net uptake of phenylalanine, conversion of phenylalanine to tyrosine (5 mumol/min) and net release of tyrosine ( approximately 5 mumol/min) occurred across the kidney. Whole-body (three-fold) and leg (two-fold) leucine transamination increased but amino acid metabolism in the kidney did not alter with diabetes or insulin deprivation. Insulin deprivation doubled endogenous glucose production, renal glucose production was unaltered by insulin deprivation and diabetes (ranging between 100 and 140 mumol/min). Renal palmitate exchange was unaltered by insulin deprivation. CONCLUSIONS/INTERPRETATION: In conclusion, kidney postabsorptively accounts for 5-10% of whole-body protein turnover, 15-20% of leucine transamination and 10-15% of endogenous glucose production, and actively converts phenylalanine to tyrosine. During insulin deprivation, leg becomes a major site for leucine transamination but insulin deprivation does not affect renal phenylalanine, leucine, palmitate or glucose metabolism. Despite its key metabolic role, insulin deprivation in type 1 diabetic patients does not alter many of these metabolic functions.
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Association Between Functional FABP2 Promoter Haplotype and Type 2 Diabetes.
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Li Y, Fisher E, Klapper M, Boeing H, Pfeiffer A, Hampe J, Schreiber S, Burwinkel B, Schrezenmeir J, Döring F
Fatty acid-binding protein 2 (FABP2) is a cytosolic protein expressed exclusively in epithelial cells of the small intestine. Some, albeit not conclusive, evidence indicates that the Thr-allele of FABP2 Ala54Thr polymorphism is associated with type 2 diabetes. More recently, common FABP2 promoter polymorphisms have shown association with postprandial increase of triglycerides, body composition and plasma lipid levels. Therefore, we reasoned that variants in the FABP2 promoter may also predispose to type 2 diabetes mellitus. In our Caucasian study population, we found three SNPs and three insertion-deletion polymorphisms that are in complete linkage disequilibrium defining promoter haplotype A and B within 1kb 5' of the FABP2 initiation codon. Haplotype calculations indicated that the FABP2 promoter and Ala54Thr variants were strongly linked. Functional analysis of promoter fragments demonstrated that haplotype difference is caused by polymorphisms within 260 bp downstream of the FABP2 initiation codon. Using a prospective case-control study nested within the EPIC-Potsdam cohort of 192 incident type 2 diabetes cases and 384 sex-/age-matched controls, male subjects carrying the FABP2 haplotype B allele showed significantly decreased risk of type 2 diabetes when adjusted for BMI (OR = 0.50, 95 % CI = 0.28 - 0.87, p < 0.05) and additional covariates (OR = 0.42, 95 % CI 0.22 - 0.81, p < 0.01). Further adjustment for the Ala54Thr polymorphism revealed an OR of 0.18 (95 % CI 0.06 - 0.49, p < 0.001). Similarly, Ala/Ala homozygote males carrying the promoter haplotype B had decreased risk (0.33, 0.11 - 0.94, p < 0.05) of type 2 diabetes after stratification for the Ala54Thr polymorphism. FABP2 promoter haplotypes or genotype combinations defined by the promoter and Ala54Thr polymorphism were not associated with BMI, body fat, leptin, HbA (1c), total cholesterol or HDL. In conclusion, our findings suggest that the functional FABP2 promoter haplotype may contribute to type 2 diabetes in a sex-specific manner.
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Upper gastrointestinal sensory-motor dysfunction in diabetes mellitus.
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Zhao J, Frokjaer JB, Drewes AM, Ejskjaer N
Gastrointestinal (GI) sensory-motor abnormalities are common in patients with diabetes mellitus and may involve any part of the GI tract. Abnormalities are frequently sub-clinical, and fortunately only rarely do severe and life-threatening problems occur. The pathogenesis of abnormal upper GI sensory-motor function in diabetes is incompletely understood and is most likely multi-factorial of origin. Diabetic autonomic neuropathy as well as acute suboptimal control of diabetes has been shown to impair GI motor and sensory function. Morphological and biomechanical remodeling of the GI wall develops during the duration of diabetes, and may contribute to motor and sensory dysfunction. In this review sensory and motility disorders of the upper GI tract in diabetes is discussed; and the morphological changes and biomechanical remodeling related to the sensory-motor dysfunction is also addressed.
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Simvastatin maintains steady patterns of GFR and improves AER and expression of slit diaphragm proteins in type II diabetes.
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Tonolo G, Velussi M, Brocco E, Abaterusso C, Carraro A, Morgia G, Satta A, Faedda R, Abhyankar A, Luthman H, Nosadini R
The factors determining the course of glomerular fitration rate (GFR) and albumin excretion rate (AER) and the expression of mRNA of slit diaphragm (SD) and podocyte proteins in microalbuminuric, hypertensive type II diabetic patients are not fully understood. GFR, AER, and SD protein mRNA were studied in 86 microalbuminuric, hypertensive, type II diabetics at baseline and after 4-year random double-blind treatment either with 40 mg simvastatin (Group 1) or with 30 g cholestyramine (Group 2) per day. Both groups had at baseline a GFR decay per year in the previous 2-4 years of 3 ml/min/1.73 m(2). Both Groups 1 and 2 showed a significant decrease of low-density lipoprotein cholesterol levels after simvastatin and cholestyramine treatment (P<0.01). No change from base line values was observed as for hs-C-reactive protein and interleukin-6. A significant decrease of 8-hydroxydeoxyguanosine urinary excretion was observed after simvastatin treatment. GFR did not change from baseline with simvstatin, whereas a decrease was observed with cholestyramine treatment (simvastatin vs cholestyramine: -0.21 vs -2.75 ml/min/1.73 m(2), P<0.01). AER decreased in Group 1 (P<0.01), but not in Group 2 patients. Real-time polymerase chain reaction measurement of mRNA SD proteins (CD2AP, FAT, Actn 4, NPHS1, and NPHS2) significantly increased in kidney biopsy specimens after simvastatin, but not cholestyramine treatment. Simvastatin, but not cholestyramine, 4-year treatment maintains steady patterns of GFR, and improves AER and expression of SD proteins in type II diabetes, despite similar hypocholesterolemic effects in circulation.Kidney International advance online publication, 17 May 2006; doi:10.1038/sj.ki.5001515.
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New insights in the treatment of ANCA-associated systemic vasculitis.
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Sinico RA, Sabadini E
The prognosis of untreated ANCA-associated systemic vasculitis (AASV) is poor with up to 90% of patients dying within 2 years. The combination of prednisone and cyclophosphamide is now established as the treatment of choice and leads to control of the disease in 80-90% of the patients. Such treatment has turned these acutely fatal diseases into chronic relapsing disorders with accumulating drug-related morbidity in over 50% of the patients, including diabetes, bladder and lympho-proliferative malignancy and infertility. Treatment of AASV can be divided into three phases: therapy for induction of remission, for maintenance of remission and therapy for refractory and relapsing disease. In addition, the treatment must be tailored to the stage and severity of the disease and a new classification of AASV was introduced: localized vasculitis, early systemic vasculitis, generalized vasculi-tis, severe renal vasculitis and refractory vasculitis. Different randomized clinical trials have been performed with the aim of optimizing the existing therapeutic regimens: some of these have been concluded, others are still ongoing. Newer therapeutic approaches are currently being tested and have involved the use of mycophenolate mofetil, anti tumour necrosis factor (TNF) drugs (anti TNF antibody infliximab and humanized soluble TNF receptor etanercept), monoclonal anti- lymphocyte antibody (anti-CD20). These new alternative therapies could be used in patients with frequent relapses, in patients who fail to achieve remission with standard induction therapy and in those with severe side effects due to cumu-lative doses of cyclophosphamide.
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The association of serum total sialic acid/total protein ratio with diabetic parameters in young type 1 diabetic patients.
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KurtoÄŸlu S, Atabek ME, Muhtaroglu S, Keskin M
Sialic acid is a terminal component of the non-reducing end of carbohydrate chains of glycoproteins and glycolipids. The purpose of this study was to estimate serum total sialic acid (TSA) concentrations and serum TSA/serum total protein (TP) ratios in young type 1 diabetic subjects and to investigate their association with diabetes-related parameters in that population. Twentyfour young type 1 diabetic patients and 20 healthy controls were enrolled in this study. Serum TSA and serum TSA/TP ratio were measured in both groups. Moreover, we looked for correlation among serum TSA, serum TSA/TP ratio and clinically relevant parameters such as urinary albumin excretion, blood pressure, diabetes duration, HbA1c, daily insulin dose, serum lipids and magnesium in type 1 diabetic patients. Serum TSA concentrations and serum TSA/TP ratio showed no statistical difference between patients and controls (p>0.05). While serum TSA concentrations only correlated with urinary albumin excretion (r=0.44, p=0.028), serum TSA/TP ratio correlated with diastolic blood pressure (r=0.48, p=0.015), diabetes duration (r=0.46, p=0.022) and urinary albumin excretion (r=0.53, p=0.007) in the diabetic subjects. We concluded that serum TSA/TP ratio might be a better indicator than serum TSA as an index of diabetic complications.
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Safety and Efficacy of Low-dose Pioglitazone (7.5 mg/day) vs. Standard-dose Pioglitazone (15 mg/day) in Japanese Women with Type 2 Diabetes Mellitus.
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Majima T, Komatsu Y, Doi K, Shigemoto M, Takagi C, Fukao A, Corners J, Nakao K
It is well known that pioglitazone, a potent thiazolidinedione, improves metabolic control. However, weight gain or peripheral edema may be of major clinical concern when using this agent. The purpose of our study was to prospectively evaluate the effects of low-dose pioglitazone (7.5 mg/day) on metabolic control, weight gain and the incidence of edema compared with a standard dose of pioglitazone (15.0 mg/day) in patients with type 2 diabetes mellitus (T2DM). Ninety-five Japanese female patients (mean age 58.410.4 years) with newly diagnosed T2DM were selected for this study. They were randomly divided into the following 2 groups according to therapy regimens, and examined every month for 6 months after diagnosis. Group A consisted of 54 patients treated with low-dose pioglitazone orally; Group B, the control-group, consisted of 41 patients treated with standard-dose pioglitazone orally. The incidence of peripheral edema was significantly much lower in group A (2/54) than in group B (11/41) (p=0.0014). In addition, % change of body weight during the 6-month treatment in group A was significantly less than that in group B (p<0.0001). On the other hand, the % change of biochemical parameters including HbA1c did not differ significantly between group A and group B, although glucose and lipid control significantly improved from baseline in both groups. Our results demonstrate the safety and efficacy of low-dose pioglitazone, suggesting that it could be another good choice of treatment for Japanese women with T2DM.
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Thyroid dysfunction and thyroid autoimmunity in Saudi type 2 diabetics.
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Akbar DH, Ahmed MM, Al-Mughales J
Diabetes mellitus and thyroid disease are common endocrine disorders in the general population. To investigate the association between thyroid dysfunction, thyroid autoimmunity and Saudi type 2 diabetics, a random sample of 100 Saudi type 2 diabetics and 100 age- and sex-matched controls were studied. The mean age was 54 years for diabetics and 55 years for controls while the male:female ratios were 1:1.6 and 1:14 respectively. GAD65ab were found in 26% diabetics and 2% controls (p=0.001). Thyroid autoimmunity were detected in 10% diabetics vs. 5% controls (p=0.05), while thyroid dysfunction was found in 16% and 7% respectively (p=0.03). In GAD65ab-positive diabetics, thyroid autoimmunity was observed in 27% vs. 4% GAD65ab-negative diabetics (p=0.02) and thyroid dysfunction was reported in 42% and 7% respectively. We conclude that thyroid dysfunction and autoimmunity are common in Saudi type 2 diabetics. Further studies are needed on the cost effectiveness of thyroid screening in diabetics.
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Feasibility of correction of insulin insufficiency after autotransplantation of splenic tissue in duodenopancreatectomy.
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Timerbulatov VM, Faiazov RR, Khasanov AG, Rakhmatullin SI, Timerbulatov SV, Saiapov MM
Autotransplantation of splenic tissue in two patients after total duodenopancreatectomy and splenectomy for trauma of the duodenum and pancreas has demonstrated positive results and stable compensation of insulin insufficiency in two cases. Experimental studies of autotransplantation of splenic tissue carried out on 20 cats and 100 rats with pancreatectomy- and alloxan-induced diabetes demonstrated good results too. This method may be regarded as the variant of repair therapy with stromal stem-cells of the spleen.
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The restorative effects of pulsed infrared light therapy on significant loss of peripheral protective sensation in patients with long-term type 1 and type 2 diabetes mellitus.
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Arnall DA, Nelson AG, López L, Sanz N, Iversen L, Sanz I, Stambaugh L, Arnall SB
Pulsed infrared light therapy (PILT) has been shown to increase peripheral sensation in diabetic patients with diabetic peripheral neuropathy (DPN). However, most studies last for very short periods, with the subjects receiving only 6-20 treatments. The purpose of this study was to evaluate the effectiveness of an eight-week course of PILT in reversing long-standing, profound DPN in patients with type 1 and type 2 diabetes. Twenty-two subjects with a diagnosis of type 1 (n=2) or type 2 (n=20) diabetes participated in the study. PILT was administered to one foot chosen at random with the other foot serving as a within-subject control (no treatment). Patients underwent 24 treatments (3 times/week, for eight weeks) for 30 min per treatment. Changes in peripheral protective sensation (PPS) were measured using Semmes-Weinstein monofilaments (SWM) ranging from 3.7 to 6.48. PILT improved PPS even in patients with long-standing chronic neuropathies whose initial pre-study sensation was not measurable with a 200-g SWM. PILT significantly improves PPS. While the exact mechanism of action is not understood, infrared light may improve peripheral neuropathies by improving foot perfusion by stimulating nitric oxide production.
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Association of cigarette smoking and tar and nicotine intake with development of type 2 diabetes mellitus in men and women from the general population: the MONICA/KORA Augsburg Cohort Study.
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Meisinger C, Döring A, Thorand B, Löwel H
AIMS/HYPOTHESIS: We examined sex-specific associations between cigarette smoking and incident type 2 diabetes mellitus in Germany. SUBJECTS, MATERIALS AND METHODS: The study was based on 5,470 men and 5,422 women (aged 25-74 years) without diabetes who participated in one of the three population-based MONICA Augsburg surveys between 1984 and 1995. Incident cases of type 2 diabetes were assessed using follow-up questionnaires. Hazard ratios (HRs) were estimated from Cox proportional hazard models. RESULTS: Up to 31 December 2002 a total of 409 cases of incident type 2 diabetes among men and 263 among women were registered. The number of cigarettes and the nicotine and tar consumption per day were associated with a significantly increased risk of type 2 diabetes among men, but not among women; this could be due to the low power of the study in women. After multivariable adjustment, the HRs for type 2 diabetes compared with never-smokers were 1.48, 2.03 and 2.10 for men smoking 1 to 14, 15 to 19 and >/=20 cigarettes/day (p for trend <0.0001) and 1.25, 1.34 and 1.37 for women smoking 1 to 9, 10 to 19 and >/=20 cigarettes/day (p for trend 0.0985). Compared with never-smokers, the HRs for increasing tar intake in men (1-167, 168-259 and >/=260 mg/day) were 1.45, 2.32 and 2.07 (p for trend <0.0001); the respective HRs in women (1-89, 90-194 and >/=195 mg/day) were 1.18, 1.57 and 1.24 (p for trend 0.1159). CONCLUSIONS/INTERPRETATION: Cigarette smoking is an important modifiable risk factor of type 2 diabetes particularly in men from the general population.
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