Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nektar Therapeutics (formerly Inhale Therapeutic Systems) has developed a pulmonary drug delivery system for insulin [HMR 4006, Exubera]. The rationale behind developing a pulmonary drug delivery system is to ensure that insulin powder is delivered deep into the lungs, where it is easily absorbed into the bloodstream, in a hand-held inhalation device. The device converts the insulin powder particles into an aerosol cloud for the patient to inhale. No propellants are used. The inhaler requires no power source and the clear chamber ensures that the patient knows immediately when all the insulin has been inhaled. Nektar Therapeutics, developers of the inhalation device and formulation process, has licensed the system to Pfizer. Under the terms of the agreement, Pfizer will lead the clinical development of inhaled insulin, while working with Nektar Therapeutics to develop the technology required for packaging the product. Pfizer has an agreement with Hoechst Marion Roussel (now Aventis Pharma) for developing, manufacturing and promoting inhaled insulin. Under the terms of the collaboration, Aventis Pharma will supply recombinant insulin to Nektar Therapeutics to process it into dry powder for incorporation into the inhaler device. Nektar Therapeutics will receive royalties on sales of inhaled insulin marketed by Pfizer and Aventis Pharma, and milestone payments and research support from Pfizer. Aventis Pharma's codename for the product is HMR 4006.Profil, a CRO in Germany, is cooperating with Pfizer/Aventis Pharma in the development of inhaled insulin. In March 2004, Pfizer and Aventis announced that the European Medicines Evaluation Agency (EMEA) accepted the filing of the MAA for inhaled insulin (Exubera) for the treatment of type 1 and type 2 diabetes mellitus. The two companies are working with the US FDA to determine the timing for the submission of the NDA in the US. Pfizer completed five pivotal phase III clinical trials with inhaled insulin in patients with type 1 and type 2 diabetes mellitus in 120 centres worldwide, and will use a fourth prototype inhaler device that is half the size of the first prototype, and has reduced manufacturing costs. Pfizer and its partner, Aventis Pharma, are conducting additional long-term pulmonary safety data studies in patients with type 1 and type 2 diabetes. Pfizer is also conducting phase III clinical trials with inhaled insulin in paediatric patients aged 6-17 years. Nektar Therapeutics is using its Advanced PEGylation technology to develop a dry powder-inhaled polyethylene glycol (PEG) formulation for delivering peptides efficiently across the lungs and to promote prolonged serum concentration of the peptide. PEG is a neutral, water-soluble, nontoxic polymer comprising any number of repeating units of ethylene oxide. PEGylation is designed to increase the size of the active molecule and ultimately improve drug performance by optimising pharmacokinetics, increasing bioavailability, and decreasing immunogenicity and dosing frequency. The investigation has begun with inhaled, long-acting (PEGylated) insulin [inhaled PEG-insulin, PEGylated insulin--Nektar], and is funded by Pfizer. Preclinical results of a dry powder formulation of inhaled PEG-insulin presented at the 63rd Scientific Sessions of the American Diabetes Association (ADA-2003) [June 2003, New Orleans, LA, USA] demonstrated prolonged systemic activity of insulin in dogs. Nektar Therapeutics was granted US patent 5,997,848 on a method for delivering inhalable insulin. The patent covers a method for delivering of 0.5-15 mg of aerosol dry powder insulin per dosing session in 1-4 individual dosages into the deep lung for systemic absorption. The patent does not specify the formulation of insulin or aerosol delivery device. Nektar Therapeutics estimated in June 2002 that Exubera could earn the company potential revenues of >200 million US dollars.
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PMID:Insulin inhalation--Pfizer/Nektar Therapeutics: HMR 4006, inhaled PEG-insulin--Nektar, PEGylated insulin--Nektar. 1513 80

This random multistage cross-sectional population survey was undertaken to determine the prevalence of type 2 diabetes mellitus (DM) in subjects aged 25 years and above in India. The study was carried out in 77 centres (42 urban and 35 rural) to reflect the size and heterogeneity of the Indian population. 18,363 (9008 male and 9355 female) subjects were studied. 10,617 (5379 males and 5238 females) were from urban areas and 7746 (3629 males and 4117 females) from rural areas. Blood samples were taken after a fast of 10-12 and 2 h after 75 g of oral glucose. Subjects were categorized as having impaired fasting glycemia (IFG) or DM using the 1997 ADA or having impaired glucose tolerance (IGT) or DM using the 1999 WHO criteria. The age- and gender-standardized prevalence rate for DM using the ADA criteria was 3.6% whilst that using the WHO criteria was 4.3% (P < 0.001). The respective standardized prevalence of DM, using the two criteria was, 4.7 and 5.6%, respectively (P < 0.001) in the urban Indian population and 2.0 and 2.7% (P < 0.02) in the rural Indian population. Using the WHO criteria, 581 subjects were newly diagnosed whilst the ADA criteria newly diagnosed 437 subjects. The respective numbers for the urban population were 425 and 323, and for the rural population were 146 and 114, respectively. The ADA criteria could diagnose 75.2, 76.0 and 73.0% of the subjects who had DM as per the WHO criteria. Of 739 Indian subjects who had IFG, 106 (14.3%) were diagnosed as having DM by the WHO criteria whilst 505 (68.3%) had values compatible with a diagnosis of IGT. Of the 536 urban subjects with IFG, 74 (13.8%) had DM and 350 (65.3%) had IGT using the WHO criteria. Of the 302 rural subjects with IFG, 32 (15.8%) had DM and 155 (76.3%) had IGT using the WHO criteria. 505 (49.9%) of 1012 Indian subjects with IGT as per the WHO criteria had IFG. 350 (47.7%) of 733 urban subjects and 155 (55.5%) of 279 rural subjects with IGT had values compatible with IFG as per the ADA criteria. Type 2 diabetes is a major health problem is India. The use of the ADA criteria would underestimate the prevalence of DM by not diagnosing subjects showing a poor response to a glucose challenge. This along with the discrepancies between subjects showing IGF or IGT could be a challenge to any prevention program.
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PMID:Comparing the ADA 1997 and the WHO 1999 criteria: Prevalence of Diabetes in India Study. 1553 28

This study compared an activation intervention to passive education in a randomized attention-control trial of 232 patients with type 2 diabetes. The activation intervention was based on Expanding Patient Involvement in Care (EPIC) trials, and was compared to time-matched passive education viewing of ADA video-tapes. Patient demographics and clinical characteristics of their diabetes were assessed with questionnaires, active involvement was assessed via ratings of taped interactions between patients and providers, and serum samples were analyzed for HbA1c. Patients in the activation condition were rated as more actively involved in discussions of diabetes self-management, and rated active involvement was predictive of improvement in glycemic control. No effect of the activation intervention was found on HbA1c. Thus, the activation intervention increased the active involvement of patients with type 2 diabetes in visits with practitioners, and active involvement led to improved glycemic control. However, the activation intervention did not improve glycemic control directly.
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PMID:Promoting glycemic control through diabetes self-management: evaluating a patient activation intervention. 1559 Feb 20

In order to determine whether the variations in the calpain-10 gene constitutes risk of type 2 diabetes (T2DM) in Chinese, the frequency of UCSNP-43, 44 in 268 adults newly diagnosed with T2DM (according to the 1999 ADA criteria) and 153 non-diabetic control subjects was investigated. For all subjects, the height, weight, waist-to-hip ratio (W/H) and blood pressure, as well as following parameters were measured: (1) 75-g oral glucose tolerance test with insulin, C-peptide, HbA1c and blood lipid profiles; (2) Genomic DNA extracted from peripheral blood lymphocytes was genotyped for UCSNP-43 (calpain-10-g. 4852 G/A) and UCSNP-44 (calpain-10-g. 4841 T/C) by sequencing a polymerase chain reaction (PCR)-amplified fragment. PCR product was selected by single strand conformation polymorphism (SSCP) and then sequenced. The results showed that there was significant difference between T2DM group and normal control group in allele frequencies, haplotype frequencies, or haplotype combinations of UCSNP-43 and -44 either. But in newly diagnosed T2DM group, it was found that the individuals with the genotype UCSNP-44 T/C + C/C had significantly increased fasting and post-challenge insulin levels (Fins and P2hIns), consistent with reduced insulin sensitivity. In the BMI> 25 subgroup, the differences were even more significant. It was demonstrated that the Calpain-10 gene polymorphism UCSNP-44 was associated with insulin sensitivity and Fins and P2hIns in newly diagnosed T2DM, although Calpain-10 doesn't appear as a major diabetes susceptible gene in this population.
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PMID:Relationship between calpain-10 gene polymorphism and insulin resistance phenotypes in Chinese. 1564 90

The objective of the study was to determine the clinical characteristics and mortality of patients with hyperglycaemic hyperosmolar syndrome (HHS) and diabetic ketoacidosis (DKA) at a Jamaican tertiary care hospital. In a retrospective study of 1560 admissions for diabetes during the period 1998-2002, 980 dockets were reviewed and 164 individuals met the ADA diagnostic criteria for DKA or HHS. Patients with HHS were older than DKA patients (64.5 years [95% CI: 60.7-68.4] versus 35.9 years [95% CI: 30.2-41.6]), but were not more likely to be non-compliant with medications, infected, or male. Overall, 24% had a mixed DKA/HHS syndrome. Most DKA patients had type 2 diabetes (62%). Only 2% of HHS and 6% of DKA/HHS patients had type 1 diabetes. Syndrome specific mortality was: DKA 6.7%, HHS 20.3%, and DKA/HHS 25% (p for trend=0.013). Mortality increased significantly with age, especially in patients > or =50 years. Significant univariate predictors of mortality were altered mental status on admission, co-existing medical disease, increasing age, older age at onset of diabetes, acute stressors, and DKA/HHS. In multivariate models, only altered mental status was significant (OR=3.59; 95% CI: 1.24-10.41). Hence, hyperglycaemic crises in a Jamaican tertiary care hospital are associated with significant mortality especially in patients who are older or with altered mental status.
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PMID:Predictors of hyperglycaemic crises and their associated mortality in Jamaica. 1645 89

We have investigated the role of haptoglobin gene polymorphisms in 129 type 2 diabetic patients and 87 non-diabetic subjects, classified by the ADA criteria, in Ghana. The diabetic subjects were recruited consecutively from the National Diabetic Management and Research Center of the University of Ghana Medical School, Korle-Bu, Accra, Ghana and were categorized by their haptoglobin phenotypes. The haptoglobin 2 allele was determined to be a risk factor for type 2 diabetes in Ghana (OR = 6.1, 95% CI = 1.8-21.2; P = .0.001) while the Hp1 allele appeared protective (OR = 0.56, 95% CI = 0.31-1.0; P = .06). The deleterious role of the Hp2 allele was further evidenced by the reduced risk associated with Hp2-1M mutant heterozygotes, who produce less Hp2 protein than the normal Hp2-1 heterozygote. (OR = 0.52, 95% CI = 0.27-1.0; P = 0.06). The subjects with the homozygous Hp2 allele were also hypertensive and overweight. There was no difference (p > 0.05) in the levels of triglycerides, total cholesterol, LDL and HDL between diabetic subjects with different haptoglobin phenotypes. We conclude that hypertensive and overweight individuals with the Hp2-2 phenotype in Ghana are at a high risk of developing type 2 diabetes and may require a more aggressive management.
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PMID:Haptoglobin 2-2 phenotype is a risk factor for type 2 diabetes in Ghana. 1673 96

This study examines relationships between patient reported outcomes (PROs) and clinical outcomes in Type 2 diabetes mellitus (T2DM). Patients at the outpatient clinics of a university hospital completed measures of generic health status (SF-12), diabetes-specific quality of life (Audit of Diabetes Dependent Quality of Life - ADDQoL), and depressive symptoms (Center for Epidemiologic Studies Depression - CES-D). Patient reported data were merged with a retrospective collection of clinical and utilization data, including HbA1C, from electronic medical records. A Charlson comorbidity score, diabetes complications score, BMI, and total number of ER and hospital visits were calculated. Usable response rate was 44.3% (n = 385). Patients were dichotomized into glycemic control levels based on the ADA recommended A1C level < 7.0, vs. >or= 7.0. The ADDQoL, PCS-12, and MCS-12 scores were separately examined as dependent variables using hierarchical regression models, with glycemic control as the primary explanatory variable, and controlling for demographics and clinical variables including comorbidities and complications. Glycemic control was not a significant predictor in any regression model. Obesity was a significant predictor leading to poorer PCS-12 and MCS-12 scores, while depressive symptoms significantly resulted in lower PCS-12, MCS-12 and ADDQoL scores. These and other factors related to self-management behaviors may contribute to a greater understanding of how to intervene with patients with T2DM. The use of such PROs alongside biomedical measures such as A1C is recommended.
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PMID:Quality of life, health status and clinical outcomes in Type 2 diabetes patients. 1703 3

The epidemic of type 2 diabetes in the latter part of the 20th and early 21st centuries and the recognition that achieving specific glycemic goals can substantially reduce morbidity, have made effective treatment of hyperglycemia a top priority. In addition, strict control of the multiple, classical and emergent cardiovascular risk factors are also important. Diabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. The development of new classes of blood glucose-lowering medications such as glitazones to supplement the classical therapies such as sulfonylureas and metformin has increased oral treatment options for type 2 diabetes. Combined therapy of two oral agents is the essential axis of type 2 diabetic patients. Early insulin therapy in combined therapy is presently an option according to ADA-2007 Standards.
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PMID:[Pharmacological recommendations in the daily metabolic control of diabetes mellitus type 2. The role of the new insulins]. 1768 72

Cardiovascular diseases continue to be the main cause of death in most industrialized countries. Endothelial dysfunction, a systemic process, is the earliest known marker of atherosclerosis and has become a major focus in acute ischemic disorders. We are investigating the hypothesis that, in these diseases, microvascular and endothelial dysfunctions occur simultaneously and precede the onset of macrovascular disease. We studied, to our knowledge for the first time in the same subjects, microvascular and endothelial functions in 11 patients with type 2 diabetes. 36 metabolic syndrome patients (NCEP-ATPIII criteria) and 25 young obese women matched with healthy controls. Micro vascular morphology and hemodynamics were evaluated non-invasively by means of nailfold videocapillaroscopy. Red blood cell velocity (RBCV, mm/s) was measured at rest and after release from 60 s of arterial occlusion (RBCVmax, mm/s) at the finger base, along with the time to reach RBCVmax (TRBCVmax, s), by video analysis with Cap Image software. Venous occlusion plethysmography was performed after intra-arterial infusions of acetylcholine and sodium nitroprusside to assess endo thelial-dependent and -independent vasodilation, respectively. We found similar results in the three groups of subjects, namely a significant decrease in RBCVmax, an increase in TRBCVmax, and a decrease in endothelial-dependent vasodilation. These findings clearly demonstrate that the two dysfunctions occur simultaneously in these groups of patients. Several mechanisms which could impair micro vascular and endothelial functions are associated with insulin resistance, and drugs that act on insulin resistance might thus be beneficial. Metformin, given to 16 first-degree relatives of patients with type 2 diabetes mellitus, who had the metabolic syndrome and normal glucose tolerance (ADA criteria), improved endothelial-dependent vasodilation and microcirculatory function. Rosiglitazone, given to 18 patients with the metabolic syndrome, enhanced vascular responses by improving endothelial function and increasing adiponectin levels. Increased triglyceride storage is often associated with insulin resistance, contributing to free fatty acid (FFA) overexposure. The two drugs tested here stimulate AMP-activated protein kinase, which promotes FFA oxidation and thus reduces oxidative stress, and might therefore attenuate endothelial lipotoxicity. The results strongly suggest that targeting micro vascular and endothelial dysfunctions in patients with metabolic disorders might help to prevent cardiovascular events, and warrant long-term clinical trials.
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PMID:[Vascular dysfunction in metabolic disorders: evaluation of some therapeutic interventions]. 1807 49

Sufficient evidence exists in relation to the association in clinical practice between disorders in the metabolism of glucose, lipoproteins, insulin action, arterial hypertension and centrally-distributed obesity. This association is named Metabolic Syndrome. Despite the existence thereof had been questioned by the ADA and EASD, it is a useful tool affording the possibility of identifying individuals at high risk of developing cardiovascular disease. Metabolic syndrome and/or its individual components are associated with a high incidence rate of cardiovascular disease. Obesity and a sedentary lifestyle are underlying risk factors along this syndrome's pathway to disease, changes in living habits therefore being a first-line intervention in the prevention and treatment of insulin resistance, hyperglycemia, aterogenic dyslipemia and arterial hypertension. Weight loss and exercise are the keys to the overall plan, one of the most important non-pharmacological cardiovascular risk reduction strategies however still being diet. Epidemiological studies have found a high intake of simple sugars, of foods having a glycemic index and of diets with a high glycemic load to be associated to insulin resistance, type II diabetes mellitus, hypertriglyceridemia and low HDL-cholesterol figures. Los saturated fat intake in favor of polyunsaturated and monounsaturated fatty acids has been implied in a reduction of the incidence of type II diabetes mellitus and dyslipemia, although the debate is ongoing. Unrefined grain fiber in the diet has been beneficial in reducing the risk of diabetes. Among the diet patterns, the Mediterranean diet has been related to a lower incidence of diabetes and a reduction in the risk of death. Studies for intervention in the prevention of type II diabetes have suggested low-fat diets (reducing saturated and trans-fats), with a high degree of fiber and low glycemic index. Clinical trials have shown diets with small amounts of carbohydrates, low glycemic index and the Mediterranean and DASH diets to be beneficial in reducing aterogenic dyslipemia. There is currently no good evidence for choosing diets with restricted carbohydrates. On the other hand, different guides recommend low-calorie diets with a low content in saturated fats, trans-fats, cholesterol and sugars in favor the eating fruits, green vegetables, unrefined grains and fish.
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PMID:[Nutrition and metabolic syndrome]. 1827 53


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