Researchers gave food rich in fat to the mouse when they were about eight months and continued until the age of two.
During this study researches have proved that when fatty food could cause inflammation of islets of Langerhans as it has been already seen in some diabetic patients but in this study now it has been confirmed by using the new mouse model. Inflammation of islets has been considered as an important factor that could trigger the risk of diabetes type 2. Studies have shown that dipeptidyl peptidase-4 (DPP4) inhibitors stimulate insulin secretion and increase beta cell mass in rodents.
After 1 month of HFD alone, the mice were given the DPP4 inhibitor vildagliptin for a further 11 months. Beta cell function and glucose tolerance were significantly improved by vildagliptin with both diets. In a unique advanced-aged HFD-induced-obesity mouse model, insulin secretion was improved and the extensive peri-insulitis prevented by chronic DPP4 inhibition. Enter your email address to subscribe to this blog and receive notifications of new posts by email. To see our content at its best we recommend upgrading if you wish to continue using IE or using another browser such as Firefox, Safari or Google Chrome.
The National Institute for Health and Clinical Excellence (NICE) said that Forxiga, or dapagliflozin, was a cost-effective option for type 2 diabetes when used in combination with the older medicine metformin, Reuters reported. Insulin Glargine is basically used as a treatment for Type-1 diabetes, a condition in which the body is not able to produce enough insulin, and as a result, is unable to control the amount of sugar in the blood stream.
In recent clinical trials, a fixed ratio combination of Insulin Glargine along with Lixisenatide, which is a GLP-1 RA was shown to have superior reduction in the average blood glucose levels as compared to past clinical trials.
Insulin Glargine is an analogue of human insulin which has been modified to provide a consistent supply of plasma insulin in those people who have been diagnosed with Type-1 and Type-2 diabetes.
Both Type-1 and Type-2 diabetes can pose major problems for the body, which is one of the reasons why diabetes is called “the silent killer”.
Products currently covered by valid US Patents are offered for R&D use in accordance with 35 USC 271(e) +A13(1). This entry was posted in Anti-Diabetic, Drug Research & Development API, Patent Expiration 2023, Therapeutic Classification and tagged anti-diabetic by admin. Our New BMJ website does not support IE6 please upgrade your browser to the latest version or use alternative browsers suggested below. Objective: To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes. Main outcome measures: Predefined clinical end points, fatal and non-fatal, related to diabetes, deaths related to diabetes, and all cause mortality. Conclusion: Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinically important reduction in the risk of deaths related to diabetes, complications related to diabetes, progression of diabetic retinopathy, and deterioration in visual acuity. Members of the study group are given at the end of the paper.Editorials by Orchard and Mogensen Papers pp 713, 720This paper was prepared for publication by Robert Turner, Rury Holman, Irene Stratton, Carole Cull, Valeria Frighi, Susan Manley, David Matthews, Andrew Neil, Heather McElroy, Eva Kohner, Charles Fox, David Hadden, and David Wright. In the general population treatment to lower blood pressure reduces the incidence of stroke and myocardial infarction, 14 15 particularly in elderly people.
We studied hypertensive patients with type 2 diabetes who had been recruited to the UK prospective diabetes study. Of the 4297 patients recruited to the 20 centres participating in the hypertension in diabetes study, 243 had either died or were lost to follow up before the start of the hypertension study in 1987 (fig 1).
TABLE I Characteristics of patients allocated to tight and less tight control of blood pressure.
Randomisation stratified for those with or without previous treatment for hypertension was performed by the coordinating centre. Captopril was usually started at a dose of 25 mg twice daily, increasing to 50 mg twice daily, and atenolol at a daily dose of 50 mg, increasing to 100 mg if required. Blood pressure (diastolic phase 5) while the patient was sitting and had rested for at least five minutes was measured by a trained nurse with a Copal UA-251 or a Takeda UA-751 electronic auscultatory blood pressure reading machine (Andrew Stephens, Brighouse, West Yorkshire) or with a Hawksley random zero sphygmomanometer (Hawksley, Lancing, Sussex) in patients with atrial fibrillation. At entry to the UK prospective diabetes study and subsequently every three years all patients had a clinical examination which included retinal colour photography, ophthalmoscopy, measurement of visual acuity, assessment of peripheral and autonomic neuropathy, chest radiography, electrocardiography, and measurement of brachial and posterior tibial blood pressure using Doppler techniques.
Visual acuity was measured with Snellen charts until 1989, after which ETDRS (early treatment of diabetic retinopathy study) charts22 were used to assess best corrected vision, with current refraction or through a pinhole. Twenty one clinical end points were predefined in the study protocol.22 All available clinical information was gathered for possible end points—for example, copies of admission notes, operation records, death certificates, and necropsy reports. Secondary outcome analyses of four additional aggregates of clinical end points were used to assess the effect of treatments on different types of vascular disease. Since a patient could in sequence have different end points, he or she could be included in more than one end point category.
Analysis was on an intention to treat basis, comparing patients allocated to tight and less tight blood pressure control. Hypoglycaemia was determined from the number of patients allocated to a treatment and continuing with it who had one or more minor or major hypoglycaemic episodes each year. Both the UK prospective diabetes study and hypertension in diabetes study received ethical approval from the appropriate committee in each centre and conformed with the guidelines of the Declarations of Helsinki (1975 and 1983).
The data monitoring and ethics committee examined the end points every six months to consider halting or modifying the study according to predetermined guidelines. The median follow up to death, the last known date at which vital status was known, or to the end of the trial was 8.4 years. In the group assigned to tight control of blood pressure patients took their allocated treatment for 77% of the total person years and did not take antihypertensive treatments for 6% of the total person years. Figure 3 shows the increasing number of antihypertensive agents required to maintain blood pressure lower than target levels. Patients allocated to tight compared with less tight control of blood pressure had a 24% reduction in risk of developing any end point related to diabetes, (P=0.0046) (figs 4 and 5). Patients in the group assigned to tight blood pressure control compared with those in the other group had a 32% reduction in risk of mortality from diseases substantially increased by diabetes (P=0.019), two thirds of which were cardiovascular diseases. The group assigned to tight blood pressure control had a non-significant reduction in risk of 21% in the aggregate end point for myocardial infarction (table 2 and fig 7). When all macrovascular diseases were combined, including myocardial infarction, sudden death, stroke, and peripheral vascular disease, the group assigned to tight blood pressure control had a 34% reduction in risk compared with the group assigned to less tight control (P=0.019). The group assigned to tight blood pressure control had a 37% reduction in risk of microvascular disease compared with the less tight group (P=0.0092) (figs 4 and 7).
There was a 56% reduction in risk of heart failure (P=0.0043) (fig 8) in the tight control group compared with the less tight control group. Neuropathy—The surrogate indices of neuropathy and autonomic neuropathy were not significantly different between the two groups. There was no significant difference between the groups in the proportion of patients who developed surrogate indices for macrovascular disease. This paper reports that patients with hypertension and type 2 diabetes assigned to tight control of blood pressure achieved a significant reduction in risk of 24% for any end points related to diabetes, 32% for death related to diabetes, 44% for stroke, and 37% for microvascular disease.
Retinopathy —The was a 34% reduction in the rate of progression of retinopathy by two or more steps using the modified ETDRS final scale. Currently developed mouse model is considered as the most accurate model to investigate the actions of different drugs on the diabetic body in comparison to past studies. We generally get the disease in middle age when we start to put on weight and live a more sedentary, and more stressful, life. All the mice become fatty and overweight and suffer a rapid rise in their blood sugar levels.
They were still obese, but had normal blood sugar, were otherwise healthy and lived longer”, said Bilal Omar. Even if it is too early to draw parallels with the diet of humans, it makes it doubtful whether a high-fat diet over a long period should be recommended, as in the LCHF diet”, said Professor Bo Ahren, another of the researchers behind the study. However, in these models hyperglycaemia has been induced early on in life and the treatment periods have been short. At multiple time points throughout the study, OGTTs were performed and beta cell area and long-term survival were evaluated. In contrast, in spite of the long treatment period, beta cell area was not significantly different between vildagliptin-treated mice and controls.
The improved survival rates for obese mice chronically treated with vildagliptin suggest that chronic DPP4 inhibition potentially results in additional quality-adjusted life-years for individuals with type 2 diabetes, which is the primary goal of any diabetes therapy.
Stem cells Could Be A Better Option For Type 1 Diabetes, Research SaysDiabetes is a disorder of pancreas in which there is increased level of sugar. It is also used for the treatment of Type-2 diabetes where the body is unable to use insulin normally. Overall, the fixed ratio combination showed to have a safety profile which reflected those of insulin Glargine and Lixisentide.
Rest assured you will get premium quality API products along with the continuous support of our team throughout the R&D process. While the drug could also be used for other medical conditions it is not to be used by patients who are experiencing diabetic ketoacidosis. Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography. 16 17 In patients with type 1 diabetes who have microalbuminuria or overt nephropathy strict control of blood pressure reduces urinary albumin excretion and deterioration in renal function. 22 23 General practitioners were asked to refer patients aged 25-65 with newly diagnosed diabetes to 23 participating centres. Other agents were added if the control criteria were not met in the group assigned to tight control despite maximum allocated treatment or in the group assigned to less tight control without drug treatment. At each visit plasma glucose concentration, blood pressure, and body weight were measured, and treatments to control blood pressure and blood glucose concentration were noted and adjusted if target values were not met. The first reading was discarded and the mean of the next three consecutive readings with a coefficient of variation below 15% was used in the study, with additional readings if required.
Retinal colour photographs of four standard 30° fields per eye (nasal, disc, macula, and temporal to macular fields) were taken plus stereophotographs of the macula. Copies of these, without reference to the patient's allocated or actual treatment, were formally presented to two independent physicians who allocated an appropriate code from the ninth revision of the international classification of diseases (ICD-9) if the criteria for any particular clinical end point had been met. These were myocardial infarction (fatal or non-fatal myocardial infarction or sudden death), stroke (fatal or non-fatal stroke), amputation or death from peripheral vascular disease, and microvascular complications (retinopathy requiring photocoagulation, vitreous haemorrhage, and fatal or non-fatal renal failure).
Patients allocated to tight control with angiotensin converting enzyme inhibitors or ? blockers were pooled in this paper for analysis.
These included a difference of three or more standard deviations by log rank test in the rate of deaths related to diabetes or deaths related to diabetes and major illness between the group assigned to tight control and that assigned to less tight control or between the group given captopril and that given atenolol.22 One of the stopping criteria was attained immediately before the scheduled end of the study. The vital status was known at the end of the trial in all patients except 14 (1%) who had emigrated and a further 33 patients (3%) who could not be contacted in the last year of the study for assessment of clinical end points. In the other group patients did not take any antihypertensive treatments for 43% of the total person years; they took an angiotensin converting enzyme inhibitor for 11% of the total person years and a ? blocker for 9%.
At nine years 29% of those assigned to tight blood pressure control required three or more agents in comparison with 11% of patients in the other group.
This group also had a 44% reduction in risk of stroke, fatal and non-fatal, compared with the group assigned to less tight blood pressure control (P=0.013).
This was partly because fewer patients required retinal photocoagulation, but the risk was still significantly reduced when retinal photocoagulation was excluded (data not shown). The cause of death in one patient in the group assigned to less tight control of blood pressure was attibuted to hypoglycaemia. Our new middle-aged mouse model has enabled us to study long-term physiological effects of the development and treatment of type 2 diabetes in a completely new way”, said Bilal Omar, one of the researchers behind the study. To explore the long-term effects of DPP4 inhibition on insulin secretion and beta cell mass, we have generated a high-fat diet (HFD)-induced-obesity model in mice of advanced age (10 months old). Mice of advanced age chronically fed an HFD displayed clear and extensive pancreatic inflammation and peri-insulitis, mainly formed by CD3-positive T cells, which were completely prevented by vildagliptin treatment.
Insulin Glargine is a synthetic version of insulin which is long lasting and works by replacing the insulin which is naturally produced by the body in order to move sugar from the blood to other parts of the body, where it is stored and used for energy. According to the researchers, the meeting of the primary objectives of this clinical trial showcases the clinical value of Insulin Glargine.
Those who have Type-2 diabetes are unable to use insulin in the proper way, resulting in an increase of sugar in the blood. 18 19 Lowering blood pressure also decreases albuminuria in type 2 diabetes,20 but whether it also reduces the risk of end stage renal disease or of cardiac disease is not known.
Patients were enrolled on the basis of the mean of three blood pressure measurements taken at consecutive clinic visits.
The suggested sequence was frusemide 20 mg daily (maximum 40 mg twice daily), slow release nifedipine 10 mg (maximum 40 mg) twice daily, methyldopa 250 mg (maximum 500 mg) twice daily, and prazosin 1 mg (maximum 5 mg) thrice daily.
If treatments and target blood pressures were not in accord with the protocol, the coordinating centre sent letters about affected patients to the clinical centres requesting appropriate action.
Monthly quality assurance measurements have shown the mean difference between Takeda and Hawksley machines to be 1 (4) mm Hg or less.
Every year a fasting blood sample was taken to measure glycated haemoglobin (haemoglobin A1c), plasma creatinine concentration, and concentrations of urea, immunoreactive insulin, and insulin antibodies; random urine samples were taken for measurement of albumin concentration. They are compared in the accompanying paper.29 Life table analyses were performed with log rank tests, and hazard ratios were obtained from Cox's proportional hazards models and used to estimate relative risks. Change in diabetic retinopathy was defined as a change of two steps (one step in both eyes or two or more steps in one eye) with a scale from the worse eye to the better eye that included retinal photocoagulation or vitreous haemorrhage as the most serious grade. The mean differences in systolic and diastolic pressures were 10 (95% confidence interval 9 to 12) mm Hg and 5 (4 to 6) mm Hg respectively.
The proportion of patients taking nifedipine was 32% in the group assigned to less tight blood pressure control and 31% and 40% in the group assigned to tight blood pressure control taking captopril and atenolol respectively. The trend to protection against microvascular disease and death related to diabetes became evident within the first three years of allocation to tight control (figs 4–7). The trend for reduced risk of fatal and non-fatal renal failure was non-significant (fig 8). At nine years of follow up the group assigned to tight blood pressure control had a 47% reduction in risk of a decrease in vision by three or more lines in both eyes measured with an ETDRS chart (P=0.004) (fig 9). There was no significant difference in plasma creatinine concentration or in the proportion of patients who had a twofold increase in plasma creatinine concentration between the two groups. There was no difference between the allocations for other surrogate indices of macrovascular disease. While the pancreas does make more insulin at the beginning to make up for the loss, over time, it is unable to keep up and cannot make enough insulin to keep blood glucose levels at a normal range. 16 25 26 Randomisation produced balanced numbers of patients allocated to the various glucose and blood pressure treatment combinations for the UK prospective diabetes study and hypertension in diabetes study.
Retinal photographs were assessed at a central grading centre by two independent assessors for the presence or absence of diabetic retinopathy. If agreement was not possible the information was submitted to a panel of two further independent assessors for final arbitration. Visual loss was defined as the best vision in either eye, deteriorating by three lines on an ETDRS chart. Cross sectional blood pressure in patients with data at each year were similar to the data in patients with nine years of follow up. There was no significant difference in the incidence of death from accidents, cancer, other specified causes or unknown causes. After nine years of follow up 29% of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures. Of the 1544 hypertensive patients, 252 were excluded and 144 patients did not enter the study. In the text relative risks are quoted as risk reductions and significance tests were two sided.
Insulin also helps move glucose (blood sugar) into cells, where it can be stored and used for energy.
Alzheimer’s Could Be Type 3 Diabetes, An Emerging RelationshipDifferent research studies have shown a clear association between diabetes and Alzheimer’s disease. Physicians recorded hypoglycaemic episodes as minor if the patient was able to treat the symptoms unaided and as major if third party or medical intervention was necessary. For aggregate end points 95% confidence intervals are quoted, whereas for single end points 99% confidence intervals are quoted to allow for potential type 1 errors. Similarly, 99% confidence intervals were used to assess surrogate end points that were measured at triennial visits. Enhanced ?-cell function and anti-inflammatory effect after chronic treatment with the dipeptidyl peptidase 4 inhibitor vildagliptin in an advanced age diet induced obesity mouse model.” 2013. Mean (SD), geometric mean (1 SD interval), or median (interquartile range) values are quoted for the biometric and biochemical variables, with values from Wilcoxon, t, or ?2 tests for comparisons. The overall values for blood pressure during a period were assessed for each patient as the mean during that period and for each allocation as the mean of patients with data in the allocation. Control of blood pressure was assessed in patients allocated to the two groups who had data at nine years of follow up. A type 1 diabetes diet is designed to provide maximum nutrition, while limiting sugar, carbohydrates, and sodium. Without proper diet, exercise, and insulin therapy, a person with type 1 diabetes could suffer adverse health effects. Health complications associated with this type of diabetes include: vision problems high blood pressure, which increases risk for heart attack, stroke, and poor circulation kidney damage nerve damage skin sores and infections, which can cause pain and may lead to tissue death Following proper dietary guidelines can help mitigate the difficulties of type 1 diabetes, keep your health free from complications, and make your life better overall. A nutritionist or dietitian can help you come up with meal plans, and create a diet that works for you in the long term. Having a well-stocked kitchen or carrying healthy snacks with you can cut down on unnecessary sugar, carbohydrates, sodium, and fat that can spike blood sugar. To maintain blood sugar levels, dont skip meals, and try to eat around the same time each day. Fruits Fruits are natural sources of sugar and should be counted as carbohydrates if youre using a diet plan. These include: most green leafy vegetables asparagus beets carrots celery cucumber onions peppers sprouts tomatoes Always choose fresh or frozen vegetables without added salt or sauces.
Carbohydrates can come in the form of beans, starchy vegetables, fruit juices, pasta, or bread.
Fruits, vegetables, nuts, and other foods travel easily and are great to have on hand when you need them.
Insulin treatment in diabetes mellitus journal|
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