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August 27th, 2011 admin Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. We have conducted a meta-analysis of genome-wide association tests of ~2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. Nine SNPs at eight loci were associated with proinsulin levels (P < 5 x 10–8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 x 10–4), improved β-cell function (P = 1.1 x 10–5), and lower risk of T2D (odds ratio 0.88; P = 7.8 x 10–6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.
Diabetes Journal publish ahead of print articles
Posted in Diabetes Signs 
Tags: associated, Association, Common, Diabetes, fasting, GenomeWide, Identifies, Insights, Into, Levels, Nine, Pathophysiology, Proinsulin, Provides, Type, Variants 
No Comments » August 23rd, 2011 admin In mice 4F, an apolipoprotein A-I mimetic peptide that restores HDL function prevents diabetes-induced atherosclerosis. We sought to determine whether HDL function is impaired in type 2 diabetic (T2D) patients and whether 4F treatment improves HDL function in T2D patient plasma in vitro.
HDL anti-inflammatory function was determined in 93 T2D patients and 31 control subjects as the ability of test HDLs to inhibit LDL-induced monocyte chemotactic activity in human aortic endothelial cell monolayers. The HDL antioxidant properties were measured using a cell-free assay that uses dichlorofluorescein diacetate. Oxidized fatty acids in HDLs were measured by liquid chromatography–tandem mass spectrometry. In subgroups of patients and control subjects, the HDL inflammatory index was repeated after incubation with L-4F.
The HDL inflammatory index was 1.42 ± 0.29 in T2D patients and 0.70 ± 0.19 in control subjects (P < 0.001). The cell-free assay was impaired in T2D patients compared with control subjects (2.03 ± 1.35 vs. 1.60 ± 0.80, P < 0.05), and also HDL intrinsic oxidation (cell-free assay without LDL) was higher in T2D patients (1,708 ± 739 vs. 1,233 ± 601 relative fluorescence units, P < 0.001). All measured oxidized fatty acids were significantly higher in the HDLs of T2D patients. There was a significant correlation between the cell-free assay values and the content of oxidized fatty acids in HDL fractions. L-4F treatment restored the HDL inflammatory index in diabetic plasma samples (from 1.26 ± 0.17 to 0.71 ± 0.11, P < 0.001) and marginally affected it in healthy subjects (from 0.81 ± 0.16 to 0.66 ± 0.10, P < 0.05).
In patients with T2D, the content of oxidized fatty acids is increased and the anti-inflammatory and antioxidant activities of HDLs are impaired.
Posted in Diabetes Signs Tags: AntiInflammatory, antioxidant, Diabetes, HDLs, Impaired, Properties, Type No Comments » August 19th, 2011 admin Previous studies have noted a specific association between type 1 diabetes and insufficient levels of vitamin D, as well as polymorphisms within genes related to vitamin D pathways. Here, we examined whether serum levels or genotypes of the vitamin D-binding protein (VDBP), a molecule key to the biologic actions of vitamin D, specifically associate with the disorder.
A retrospective, cross-sectional analysis of VDBP levels used samples from 472 individuals of similar age and sex distribution, including 153 control subjects, 203 patients with type 1 diabetes, and 116 first-degree relatives of type 1 diabetic patients. Single nucleotide polymorphism (SNP) typing for VDBP polymorphisms (SNP rs4588 and rs7041) was performed on this cohort to determine potential genetic correlations. In addition, SNP analysis of a second sample set of banked DNA samples from 1,502 type 1 diabetic patients and 1,880 control subjects also was used to determine genotype frequencies.
Serum VDBP levels were highest in healthy control subjects (median 423.5 µg/mL [range 193.5–4,345.0; interquartile range 354.1–586]), intermediate in first-degree relatives (402.9 µg/mL [204.7–4,850.0; 329.6–492.4]), and lowest in type 1 diabetic patients (385.3 µg/mL [99.3–1,305.0; 328.3–473.0]; P = 0.003 vs. control subjects). VDBP levels did not associate with serum vitamin D levels, age, or disease duration. However, VDBP levels were, overall, lower in male subjects (374.7 µg/mL [188.9–1,602.0; 326.9–449.9]) than female subjects (433.4 µg/mL [99.3–4,850.0; 359.4–567.8]; P < 0.0001). It is noteworthy that no differences in genotype frequencies of the VDBP polymorphisms were associated with serum VDBP levels or between type 1 diabetic patients and control subjects.
Serum VDBP levels are decreased in those with type 1 diabetes. These studies suggest that multiple components in the metabolic pathway of vitamin D may be altered in type 1 diabetes and, collectively, have the potential to influence disease pathogenesis.
Posted in Diabetes Signs Tags: associated, DBinding, Diabetes, Levels, Protein, Reduced, Serum, Type, Vitamin No Comments » July 25th, 2011 admin Circulating levels of soluble receptor for advanced glycation end products (sRAGE) likely comprises both a secreted isoform (esRAGE) and wild-type RAGE cleaved from the cell membrane. Both sRAGE and esRAGE have been proposed as biomarkers of cardiovascular disease (CVD) but prospective data are limited. We examined the relationship of sRAGE and esRAGE to incident coronary heart disease (CHD) and stroke in type 2 diabetic patients followed for 3.9 years in a trial of atorvastatin: the Collaborative Atorvastatin Diabetes Study (CARDS).
We used a nested case control design sampling all incident cases of CVD with available plasma and randomly selecting three control subjects, who were free of CVD throughout follow-up, per case. Analysis was by Cox regression with adjustment for treatment allocation and relevant covariates.
sRAGE and esRAGE were strongly correlated ( = 0.88) and were both higher in those with lower BMI (P < 0.001), higher adiponectin (P < 0.001), lower eGFR (P = 0.009), and white ethnicity (P < 0.001). Both sRAGE and esRAGE were associated with incident CHD events, independently of treatment allocation and the above factors; hazard ratio (HR) = 1.74 (95% CI 1.25–2.41; P = 0.002) for a doubling of the sRAGE level; HR = 1.45 (1.11–1.89; P = 0.006) for a doubling of the esRAGE level. There was no significant association with stroke; HR for sRAGE = 0.66 (0.38–1.14). Atorvastatin, 10 mg daily, did not alter sRAGE.
Higher levels of sRAGE and esRAGE are associated with incident CHD but not stroke in type 2 diabetes.
Posted in Diabetes Signs Tags: Advanced, Analysis, Biomarkers, CARDS, Coronary, Diabetes, Disease, Endogenous, Endproducts, from, Glycation, Heart, Patients, Predictive, Receptor, Risk, Secretory, Soluble, Total, Trial, Type No Comments » July 23rd, 2011 admin Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced that it has initiated a Phase 1 clinical study for ISIS-PTP1BRx, an antisense drug for the treatment of type 2 diabetes targeting protein tyrosine phosphatase-1B, PTP-1B. ISIS-PTP1BRx is designed to increase the body’s sensitivity to the natural hormone insulin, resulting in better glucose control for patients with type 2 diabetes…
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Posted in Diabetes Signs Tags: Diabetes, Initiates, Isis, ISISPTP1BRx, Phase, Study, Treat, Type No Comments » July 18th, 2011 admin 
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Posted in Diabetes Signs Tags: Before, Children, Controlling, Diabetes, Diagnose, Effectively, Even, Managing, Preventing, starts, Symptoms, Tips, Type, Women No Comments » May 25th, 2011 admin Question by Slippery Sally!: If its early type 1 diabetes would she have “normal” numbers too?
My 10 year old was diagnosed with “pre-diabetes” but from what I have been reading and the answers I have been getting here say it could be early signs of Type 1 diabetes. The “honeymoon” phase I think they said. We have taken a few bs readings and she has had normal fasting readings. Her fastings have been in the 80′s and 90′s which from my research are normal. Her after dinner numbers have been over 150 most of the time. The highest we have seen so far is 168 but have had a few readings in the 160′s and 150′s. So could it be that she is a Type 1 diabetic in the early stages even though she has some normal readings?
Best answer:
Answer by Frosty
Type 1 diabetics produce no to very trace amounts of insulin, certainly not enough to have a normal range for fasting if after meal (2 hours after) the blood sugar readings are in the 160′s. I know that the treatment for diabetes can be different for children so if you are having any questions the doctors would be best to help you to learn what would apply to your daughter. But this does not seem to me that she is more than pre-diabetic from what info you have given. Diabetes affects people in many ways and it is virtuously impossible to make a generalized statement on it without knowing all of the background for her case. With the research and self education that you are doing, I know that she will be able to fight this disease effectively. Best of luck and remember that your doctor will be most happy with helping you to learn more.
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May 19th, 2011 admin Type 1 diabetes leads to impairments in growth, function, and regenerative capacity of skeletal muscle; however, the underlying mechanisms have not been clearly defined.
With the use of Ins2WT/C96Y mice (model of adolescent-onset type 1 diabetes), muscle regeneration was characterized in terms of muscle mass, myofiber size (cross-sectional area), and protein expression. Blood plasma was analyzed for glucose, nonesterified fatty acids, insulin, and plasminogen activator inhibitor-1 (PAI-1). PAI-039, an effective inhibitor of PAI-1, was orally administered to determine if PAI-1 was attenuating muscle regeneration in Ins2WT/C96Y mice.
Ins2WT/C96Y mice exposed to 1 or 8 weeks of untreated type 1 diabetes before chemically induced muscle injury display significant impairments in their regenerative capacity as demonstrated by decreased muscle mass, myofiber cross-sectional area, myogenin, and Myh3 expression. PAI-1, a physiologic inhibitor of the fibrinolytic system and primary contributor to other diabetes complications, was more than twofold increased within 2 weeks of diabetes onset and remained elevated throughout the experimental period. Consistent with increased circulating PAI-1, regenerating muscles of diabetic mice exhibited excessive collagen levels at 5 and 10 days postinjury with concomitant decreases in active urokinase plasminogen activator and matrix metalloproteinase-9. Pharmacologic inhibition of PAI-1 with orally administered PAI-039 rescued the early regenerative impairments in noninsulin-treated Ins2WT/C96Y mice.
Taken together, these data illustrate that the pharmacologic inhibition of elevated PAI-1 restores the early impairments in skeletal muscle repair observed in type 1 diabetes and suggests that early interventional studies targeting PAI-1 may be warranted to ensure optimal growth and repair in adolescent diabetic skeletal muscle.
Posted in Diabetes Signs Tags: Activator, Diabetic, Inhibition, Inhibitor1, Mice, Muscle, Plasminogen, Regeneration, Restores, Skeletal, Type, Untreated No Comments » May 17th, 2011 admin Question by Esmee S: How often is “frequent urination for type 1 diabetes?”?
I’m doing a research project on Type 1 Diabetes (Juvenile Diabetes) and I need to know symptoms. One thing I need to write is how often “frequent urinaton” is. Like, once an hour, twice an hour, once every two hours, ect. Help, please! This is worth 75% of my overall Science grade.
Best answer:
Answer by m88b
frequent urination (polyuria)…. before i was diagnosed with type 1 i would go at least once an hour…but i would go twice an hour a lot too….a few times it was every 15 minutes..and i was getting up 4 or 5 times a night to go (this was between midnight and about 10am)
another symptom is being tired ALL the time. i would sleep for 12 hours and still feel really tired when i got up.
unexplained weight loss is another symptom. i lost 40lbs in 2 months
being really hungry (polyphagia) is another one. i dont remember having this symptom…i was the opposite…i basically lost my appitite for food…all i wanted was something to drink
being thirsty (polydipsia) is another symptom. however much u drink it seems u can never quench your thirst. i could drink two 20oz bottles of water in 15 minutes and still feel super thirsty
anything else? the three P’s are the main ones (polyuria, polyphagia and polydipsia)….but theres almost always more symptoms that go along with them..ya wanna know those to?
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