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Adult-onset diabetes [keywords]
- Comparison of UV spectrophotometry and high performance liquid chromatography methods for the determination of repaglinide in tablets. [Journal Article]
- Pharm Methods 2012 Jul; 3(2):68-72.
Repaglinide is a miglitinide class of antidiabetic drug used for the treatment of type 2 diabetes mellitus. A fast and reliable method for the determination of repaglinide was highly desirable to support formulation screening and quality control.UV spectrophotometric and reversed-phase high performance liquid chromatography (RP-HPLC) methods were developed for determination of repaglinide in the tablet dosage form.The UV spectrum recorded between 200 400 nm using methanol as solvent and the wavelength 241 nm was selected for the determination of repaglinide. RP-HPLC analysis was carried out using Agilent TC-C18 (2) column and mobile phase composed of methanol and water (80:20 v/v, pH adjusted to 3.5 with orthophosphoric acid) at a flow rate of 1.0 ml/min. Parameters such as linearity, precision, accuracy, recovery, specificity and ruggedness are studied as reported in the International Conference on Harmonization (ICH) guidelines.The developed methods illustrated excellent linearity (r(2) > 0.999) in the concentration range of 5-30 μg/ml and 5-50 μg/ml for UV spectrophotometric and HPLC methods, respectively. Precision (%R.S.D < 1.50) and mean recoveries were found in the range of 99.63-100.45% for UV spectrophotometric method and 99.71-100.25% for HPLC method which shows accuracy of the methods.The developed methods were found to be reliable, simple, fast, accurate and successfully used for the quality control of repaglinide as a bulk drug and in pharmaceutical formulations.
- Prediction of morbidity and mortality in patients with type 2 diabetes. [Journal Article]
- PeerJ 2013.:e87.
Introduction.The objective of this study was to create a tool that accurately predicts the risk of morbidity and mortality in patients with type 2 diabetes according to an oral hypoglycemic agent. Materials and Methods. The model was based on a cohort of 33,067 patients with type 2 diabetes who were prescribed a single oral hypoglycemic agent at the Cleveland Clinic between 1998 and 2006. Competing risk regression models were created for coronary heart disease (CHD), heart failure, and stroke, while a Cox regression model was created for mortality. Propensity scores were used to account for possible treatment bias. A prediction tool was created and internally validated using tenfold cross-validation. The results were compared to a Framingham model and a model based on the United Kingdom Prospective Diabetes Study (UKPDS) for CHD and stroke, respectively. Results and Discussion. Median follow-up for the mortality outcome was 769 days. The numbers of patients experiencing events were as follows: CHD (3062), heart failure (1408), stroke (1451), and mortality (3661). The prediction tools demonstrated the following concordance indices (c-statistics) for the specific outcomes: CHD (0.730), heart failure (0.753), stroke (0.688), and mortality (0.719). The prediction tool was superior to the Framingham model at predicting CHD and was at least as accurate as the UKPDS model at predicting stroke.
Conclusions.We created an accurate tool for predicting the risk of stroke, coronary heart disease, heart failure, and death in patients with type 2 diabetes. The calculator is available online at http://rcalc.ccf.org under the heading "Type 2 Diabetes" and entitled, "Predicting 5-Year Morbidity and Mortality." This may be a valuable tool to aid the clinician's choice of an oral hypoglycemic, to better inform patients, and to motivate dialogue between physician and patient.
- Association Between Remission of Macroalbuminuria and Preservation of Renal Function in Patients With Type 2 Diabetes Mellitus With Overt Proteinuria. [JOURNAL ARTICLE]
- Diabetes Care 2013 Jun 18.
OBJECTIVEStudies on the rate of remission of macroalbuminuria in patients with type 2 diabetes mellitus (T2DM) and the effects of reduction in albuminuria on renal prognosis in a primary care setting are absolutely lacking.RESEARCH DESIGN AND
METHODSA total of 211 T2DM patients with albuminuria ≥300 mg/g were enrolled in a prospective observational study (mean of 4.5 years). The incidence of patients with remission of macroalbuminuria at every 1-year study time point after starting intensified diabetes treatment and the factors associated with remission were evaluated. The association of reduction in albuminuria with renal events (doubling of serum creatinine and end-stage renal disease) was also investigated.
RESULTSDuring the 5-year study period, remission to microalbuminuria occurred in 116 patients and the 5-year cumulative incidence was 58.3%. Notably, most cases (82.8%) obtained remission at the 1-year study time point. The remission rate increased with achieving therapeutic targets for blood pressure and blood glucose. Remission and reduction in albuminuria of ≥50% were associated with preservation of renal function. In particular, patients who obtained both remission and 50% reduction at the 1-year study time point exhibited a significantly reduced risk for renal events as compared with those with no remission and no reduction (adjusted hazard ratio 0.30 [95% CI 0.12-0.76]).
CONCLUSIONSRemission of macroalbuminuria occurs frequently and is associated with the preservation of renal function in T2DM patients. The initial adequate diabetes treatment aimed at reducing albuminuria may lead to improved renal prognosis in the primary care setting.
- Changes in Red Meat Consumption and Subsequent Risk of Type 2 Diabetes Mellitus: Three Cohorts of US Men and Women. [JOURNAL ARTICLE]
- JAMA Intern Med 2013 Jun 17.:1-8.
IMPORTANCE Red meat consumption has been consistently associated with an increased risk of type 2 diabetes mellitus (T2DM). However, whether changes in red meat intake are related to subsequent T2DM risk remains unknown.
OBJECTIVETo evaluate the association between changes in red meat consumption during a 4-year period and subsequent 4-year risk of T2DM in US adults. DESIGN AND SETTING Three prospective cohort studies in US men and women. PARTICIPANTS We followed up 26 357 men in the Health Professionals Follow-up Study (1986-2006), 48 709 women in the Nurses' Health Study (1986-2006), and 74 077 women in the Nurses' Health Study II (1991-2007). Diet was assessed by validated food frequency questionnaires and updated every 4 years. Time-dependent Cox proportional hazards regression models were used to calculate hazard ratios with adjustment for age, family history, race, marital status, initial red meat consumption, smoking status, and initial and changes in other lifestyle factors (physical activity, alcohol intake, total energy intake, and diet quality). Results across cohorts were pooled by an inverse variance-weighted, fixed-effect meta-analysis. MAIN OUTCOMES AND MEASURES Incident T2DM cases validated by supplementary questionnaires.
RESULTSDuring 1 965 824 person-years of follow-up, we documented 7540 incident T2DM cases. In the multivariate-adjusted models, increasing red meat intake during a 4-year interval was associated with an elevated risk of T2DM during the subsequent 4 years in each cohort (all P < .001 for trend). Compared with the reference group of no change in red meat intake, increasing red meat intake of more than 0.50 servings per day was associated with a 48% (pooled hazard ratio, 1.48; 95% CI, 1.37-1.59) elevated risk in the subsequent 4-year period, and the association was modestly attenuated after further adjustment for initial body mass index and concurrent weight gain (1.30; 95% CI, 1.21-1.41). Reducing red meat consumption by more than 0.50 servings per day from baseline to the first 4 years of follow-up was associated with a 14% (pooled hazard ratio, 0.86; 95% CI, 0.80-0.93) lower risk during the subsequent entire follow-up through 2006 or 2007.
CONCLUSIONSAND RELEVANCE Increasing red meat consumption over time is associated with an elevated subsequent risk of T2DM, and the association is partly mediated by body weight. Our results add further evidence that limiting red meat consumption over time confers benefits for T2DM prevention.
- Serum uric acid in relation to serum 1,5-anhydroglucitol levels in patients with and without type 2 diabetes mellitus. [JOURNAL ARTICLE]
- Clin Biochem 2013 Jun 15.
OBJECTIVES:The aim of this study was to examine the relationship between serum levels of uric acid (UA) and 1,5-anhydroglucitol (1,5-AG) in elderly subjects (60 years or older; mean age, 73.0 ± 7.2 years) with and without type 2 diabetes mellitus (DM).
METHODS:Subjects with DM (n = 97) and without DM (n = 360) were recruited from among our outpatients (estimated glomerular filtration rate ≥ 45 ml/min/1.73 m(2), and urine protein equivalent to < 1.0 g/l), and a cross-sectional study was performed with simple linear regression and stepwise multiple linear regression analyses.
RESULTS:The mean serum UA levels of men were significantly higher than those of women in both groups. The mean serum 1,5-AG levels of men were significantly higher than those of women in the non-DM group. There were positive correlations (indicated by Pearson's correlation coefficients) between serum UA levels and 1,5-anhydroglucitol levels in all patients and in both men and women. Simple linear regression and multiple linear regression analyses showed that the serum 1,5-AG levels were significantly and positively correlated with the serum UA level in both the non-DM group and the DM group. In the non-DM group, HbA1c levels, as well as 1,5-AG levels, were positively correlated with serum UA levels. Furthermore, the correlation between 1,5-AG and UA levels was stronger in subjects with DM than in subjects without DM.
CONCLUSIONS:These results suggest that the serum 1,5-AG level is an independent factor associated with serum UA levels in the nondiabetic state, as in DM.
- Brain metabolite changes in patients with type 2 diabetes and cerebral infarction using proton magnetic resonance spectroscopy. [JOURNAL ARTICLE]
- Int J Neurosci 2013 Jun 19.
Abstract The aim of this study was to investigate the possible brain metabolic alterations in patients with type 2 diabetes mellitus (T2-DM) and cerebral infarction using proton magnetic resonance spectroscopy (MRS). Thirty four patients with type 2 diabetes mellitus and cerebral infarction (DMCI) were scanned along with thirty three patients with non-diabetic cerebral infarction (NDCI) on a 1.5-T MRI/MRS imager. Voxels were placed in the infarcted area and the contralateral normal area in the basal ganglia. N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr and lactate (Lac)/Cr ratios were calculated. Cerebral NAA/Cr ratios in the infarcted area were lower than those in the contralateral normal area of the NDCI group. There was a significant decrease in NAA/Cr in the infarcted area of the DMCI group as compared to the infarcted area of the NDCI group. NAA/Cr ratios in the contralateral normal area of DMCI group were lower than those of the NDCI group. Lac/Cr ratios were increased in the infarcted area of both the DMCI group and NDCI group, and Lac/Cr ratios tended to be higher in the infarcted area of the DMCI group than those of the NDCI group. HbA1c levels were negatively correlated with NAA/Cr ratios. The study suggested that the metabolite changes were different between DMCI patients and NDCI patients, which may provide important information in the treatment of DMCI.
- Exercise to preserve beta cell function in recent-onset type 1 diabetes mellitus (EXTOD) - a study protocol for a pilot randomized controlled trial. [JOURNAL ARTICLE]
- Trials 2013 Jun 18; 14(1):180.
BACKGROUND:Exercise has a beta cell preserving effect in patients with type 2 diabetes. This benefit of exercise has not been examined in type 1 diabetes. Significant beta cell function is present at the time of diagnosis of type 1 diabetes and therefore studies of beta cell preservation are ideally conducted immediately after diagnosis.Many of the variables required to design and power such a study are currently unknown. The aim of EXTOD is to obtain the information required to design a formal study of exercise and beta cell preservation in newly diagnosed patients with type 1 diabetes.
METHODS:Barriers to exercise will initially be assessed in a qualitative study of newly diagnosed patients. Then, sixty newly diagnosed adult type 1 diabetes patients will be randomized to either conventional treatment or exercise, stratified on beta cell function and fitness. The exercise group will be encouraged to increase their level of activity to a minimum of 150 minutes of moderate to vigorous intensity exercise per week, aiming for 240 minutes per week of exercise for 12 months. Beta cell function will be measured by meal-stimulated C peptide. Primary outcomes are recruitment, adherence to exercise, loss to follow-up, and exercise levels in the non-intervention arm (contamination). The secondary outcome of the study is rate of loss of beta cell function.
DISCUSSION:The outcomes of the EXTOD study will help define the barriers, uptake and benefits of exercise in adults newly diagnosed with type 1 diabetes. This information will enable design of a formal study to assess the effect of exercise on beta cell preservation in newly diagnosed patients with type 1 diabetes.Trial registration: Current controlled trials ISRCTN91388505.
- Glucagon-like peptide-1 (GLP-1) and protective effects in cardiovascular disease: a new therapeutic approach for myocardial protection. [JOURNAL ARTICLE]
- Cardiovasc Diabetol 2013 Jun 18; 12(1):90.
Glucagon-like peptide-1 (GLP-1) is a member of the proglucagon incretin family implicated in the control of appetite and satiety. GLP-1 has insulinotropic, insulinomimetic, and glucagonostatic effects, thereby exerting multiple complementary actions to lower blood glucose in subjects with type 2 diabetes mellitus. A major advantage over conventional insulin is the fact that the insulinotropic actions of GLP-1 are dependent upon ambient glucose concentration, mitigating the risks of hypoglycemia. Recently, the crucial role of GLP-1 in cardiovascular disease has been suggested in both preclinical and clinical studies. The experimental data indicate GLP-1 and its analogs to have direct effects on the cardiovascular system, in addition to their classic glucoregulatory actions. Clinically, beneficial effects of GLP-1 have also been demonstrated in patients with myocardial ischemia and heart failure. GLP-1 has recently been demonstrated to be a more effective alternative in treating myocardial injury. This paper provides a review on the current evidence supporting the use of GLP-1 in experimental animal models and human trials with the ischemic and non-ischemic heart and discusses their molecular mechanisms and potential as a new therapeutic approach.
- Differences Between Diabetes Patients Who Are Interested or Not in the Use of a Patient Web Portal. [JOURNAL ARTICLE]
- Diabetes Technol Ther 2013 Jun 18.