Short-term intensive insulin therapy in type 2 diabetes mellitus,pw 50 70cc kit,diabetes mellitus treatment guidelines pdf jama - PDF Books

Canadian Diabetes Care Guide is here to help you stay healthy & help you successfully manage your diabetes. Type 2 diabetes (T2DM) is a chronic complex disease that poses many challenges for the healthcare provider and patient.
Data from the UKPDS (2) trials has indicated the importance of tight metabolic control in delaying or preventing the progression of T2DM complications. The T2DM is a progressive disease characterized by insulin resistance (IR), progressive reduction in ?-cell mass and dysfunction resulting in worsening hyperglycemia over time. Growing evidence suggests that deterioration in ?-cell function occurs before IGT and hyperglycemia become apparent and may be the primary defect in many people with diabetes (11). The evolution of ?-cell dysfunction in T2DM progression has been proposed by Weir (13) in 5 stages.
There are several genetic and environmental factors contributing to the progressive loss of ?-cell function in T2DM. Both Retnakaran (14) and Tibaldi (11) noted that first treating hyperglycemia with insulin may alleviate glucotoxicity and lipotoxicity, which are known to adversely affect ?-cell function and that insulin may exert antiapoptotic effects. Studies show that when short-term intensive insulin therapy (IIT) was implemented early in the course of T2DM, glycemic remission is sometimes induced wherein patients are able to maintain normoglycemia without any anti-diabetic agents.
Studies have shown that, the degree of improvement in response to short-term IIT varies between patients.
Two sets of reviews looking at implementation of short-term IIT early in the course of T2DM by either CSII or MDI were performed at Mt. Clinical studies have consistently shown that short-term IIT improves ?-cell function and that euglycemia can be maintained for a long time after IIT is completed.
Support for the importance of residual underlying ?-cell function observed from the studies of short-term IIT are first, patients who respond positively (achieve sustained euglycemia) have required less exogenous insulin during intensive therapy than their peers, suggestive of a comparatively greater contribution of endogenous insulin secretion. To avoid the increasing ?-cell failure, the complication associated with hyperglycemia and the burden of T2DM, it is desirable to maintain ?-cell function for as long as possible after the timely diagnosis of diabetes.
Contrary to popular perception of both patients and providers, a short-course of IIT can result in significant improvement in QOL and treatment satisfaction, demonstrating the patient acceptability of early insulin therapy.
We are now in the process of accepting participants to join our study and help determine if it is possible to preserve and maintain pancreatic ?-cell dysfunction for longer duration, and change the natural course of T2DM. Haysook Choi, BSc.N, RN, CDE is a registered nurse with nineteen years’ experience as a Diabetes Educator and has dedicated the last nine years to clinical diabetes research.
In 2004 she changed her focus from clinical practice to research in endocrinology and presently works as a research nurse coordinator.
The Canadian Diabetes Care Guide is a digest sized magazine and online resource written by Diabetes Professionals for people with diabetes, Canadian’s being among a growing number of newly diagnosed around the world. Sinai Hospital in Toronto, are currently conducting a clinical trial aimed at preservation of pancreatic ?-cell function and achievement of remission of diabetes through the short-term use of intensive insulin therapy. 80% of Canadians with diabetes will die from cardiovascular disease while others are at high risk for complications and premature death. The UKPDS study (2) has shown that ?-cell function deteriorates progressively over time in people with T2DM, irrespective of lifestyle and pharmacological interventions.
Furthermore, the long term observational studies EDIC (DCCT-10 year follow-up) and UKPDS-10 year follow-up (8), have shown that a “metabolic memory” exists where the benefits of initial tight metabolic control are carried forward for another 10 years even though the control of diabetes was not so intense during the observational period. The most common cause of IR is obesity since there is decreased ability of muscle and fat tissues to take up and metabolize glucose in response to insulin. Stage 1 is ?-cell compensation: insulin secretion increases to maintain normoglycemia to compensate for IR resulting from obesity, physical inactivity and genetic predisposition.
In Tibaldi’s (11) review, the acquired factors such as, glucotoxicity from chronic exposure to hyperglycemia can prompt ?-cell apoptosis from glucose-induced toxicity causing continuous decline of ?-cell function in T2DM. Therefore timing may be an important factor when initiating insulin to improve ?-cell function: early initiation of intensive insulin therapy appears to delay the progression of ?-cell dysfunction. Sinai Hospital with 34 participants with a mean duration of T2DM of 5.9 years underwent 4-8 weeks of IIT, with a 4-h meal test administered at baseline and at 1 day post-IIT. Sinai Hospital, Toronto.   The goal of this treatment strategy was achievement of “glycemic remission” wherein patients could maintain normal glucose levels without any antihyperglycemic medication after cessation of the short course of IIT. Second, when receiving IIT early in the course of T2DM, very little hypoglycemia is experienced despite targeting near-normal glycemic control. Studies have shown that early IIT in early T2DM can increase insulin sensitivity at both skeletal muscle and liver where its effects include suppression of hepatic gluconeogenesis and reduction in liver fat content, improved ?-cell function and reduction in IR. The inclusion criteria for this study are: T2DM for 0-5 year, on metformin only or lifestyle to treat diabetes. Intensive blood-glucose control with sulfonylurea or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Diabetes Management in Canada:  Baseline results of the Group Practice Diabetes Management Study. Glycemic control and morbidity in the Canadian primary care setting (results of the diabetes in Canada evaluation study). What’s so tough about taking insulin?  Addressing the problem of psychological insulin resistance in type 2 diabetes. Beta-cell function declines within the first year postpartum in women with recent glucose intolerance in pregnancy.


Short-term intensified insulin treatment in type 2 diabetes: long-term effects on ?-cell function. Effect of intensive insulin therapy on ?–cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomized parallel-group trial. Determinants of reversibility of beta-cell dysfunction in response to short-term intensive insulin therapy in patients with early type 2 diabetes. Short-term intensive insulin therapy in type 2 diabetes mellitus: a systemic review and meta-analysis. Whether it’s patients in British Columbia, diabetics in Ontario, diabetics in Quebec or in Maritimes, the guide helps cover the basics of monitoring, moving towards a healthy lifestyle and diet. Through this study, participants will gain greater knowledge about diabetes and the impacts of lifestyle management on their glucose level.
Not only is diabetes a personal challenge for people with the disease, it is also a tremendous financial burden for society as a whole. This study also showed that only a fraction of pancreatic islet function remained at the time of diagnosis. In ACCORD (9) and ADVANCE (10) trial, the participant’s glucose control at baseline of the study was poor and likely not at optimal levels for some time before entry in the trial. Not all patients with IR will develop diabetes, however, as long as their ?-cells can compensate by producing extra insulin to meet their metabolic needs and, since IR is relatively stable over the course of T2DM, it is unlikely to account for the continued long-term progressive nature of T2DM. Thus, there may be a window of opportunity for treatment where intensive insulin therapy may slow or prevent further progression of T2DM.
In Retnakaran et al.’s review (14), the vast majority of these newly diagnosed patients were able to achieve this “glycemic remission” (80-97%). Additionally, there is heterogeneity in the patient response as seen by varying durations of the euglycemia period post IIT. This is very different from the usual experience in clinical practice setting where there is an increased risk of hypoglycemia as one approaches normoglycemia when administering insulin therapy late in the course of disease. Thus, insulin therapy needs to be introduced at an early stage in the natural history of T2DM, when sufficient ?-cell mass remains to enable functional improvement with the alleviation of reversible glucotoxicity and lipotoxicity.
The participants will be supported throughout insulin therapy to gain confidence in their ability to work with this treatment, thus counteracting psychological insulin resistance and resulting in more effective healthcare. Diabetes currently costs our healthcare system and our economy $11.7 billion and will cost Canadians about $16 billion annually by 2020 (1). Currently, T2DM is usually managed by a stepwise introduction of lifestyle interventions, oral agents alone and in combination, and finally insulin. Instead, the development of T2DM is caused by the inability of ?-cells to adequately compensate for IR, which may be a consequence of ?-cell dysfunction and ?-cell loss (11). In his study, women with gestational diabetes and those with gestational impaired glucose tolerance exhibited declining ?-cell function in the first year postpartum despite stable rates of dysglycemia 3-12 months postpartum. Stage 2 is stable ?-cell adaptation: glucose levels start to rise due to loss of ?-cell mass and initial disruption of ?-cell function. The Primary end point was the time of glycemic remission and remission rate at 1 year after short-term IIT. Sinai Hospital sought to characterize the determinants of improvements in ?–cell function in response to short-term IIT in early T2DM. Furthermore, euglycemia persisted for 1 year in about 40% of the subjects from these studies and has continued for up to 2 years or longer in some cases. Retnakaran et al (14) propose that predictors of a positive response to short-term IIT can be divided into 3 groups based on their timing.  1.
This is likely because only ?-cells can finely regulate insulin secretion to achieve normal glycemic control without hypoglycemia (14). Sinai Hospital reported significant improvements in physical functioning, general health, general mental health, global health perception, and diabetes worry and treatment satisfaction (19). Unfortunately, existing management protocols have failed to achieve and maintain the glycemic levels necessary to provide optimal healthcare for people with diabetes (3, 4, 5). Clear evidence exists of the importance of tight glucose control and a good “metabolic memory” in the prevention and delayed progression of chronic diabetes cardiovascular complications.
Thus, ?-cell dysfunction progresses in the early stages of postpartum in women with a history of gestational dysglycemia and is likely a pathophysiologic factor contributing to the development of T2DM. Another factor is lipotoxicity due to increased circulating free fatty acid and dyslipidemia that are commonly seen in patients with diabetes, especially obese individuals with abdominal adiposity. From this study, it was concluded that the clinical response to short-term IIT is variable, consistent with the heterogeneity of T2DM. Sixty-three patients with mean 3.0 years duration of T2DM underwent 4 weeks of IIT with a 75gm oral glucose tolerance test administered at baseline and 1-day post-IIT.
Baseline predictors: better glycemic control, higher late-phase insulin secretion and shorter duration of diabetes may all reflect greater residual ?-cell function. However, studies have also shown that euglycemia achieved after short-term IIT in early T2DM is temporary and glucose levels eventually rise. Furthermore, due to many factors, oral antihyperglycemic agents were preferred instead of insulin injections even when insulin therapy was clearly the optimal treatment option. This study provided the unique opportunity to identify a patient population where the early evolution of ?-cell dysfunction unfolds prior to the development of diabetes or pre-diabetes.


In healthy individuals, elevated free fatty acids may also increase IR and typically prompt enhanced insulin secretion. The responders who achieved positive response to the short-term IIT had, at baseline, higher c-peptide and lower glucose levels during the latter stages (180-240 minutes) of the meal test than the non-responders. Overall, these clinical studies have demonstrated that short-term IIT can have long-lasting effects on glycemic control in patients with newly diagnosed T2DM.
Additionally, higher BMI and IR may indicate a greater contribution of secretory stress (rather than ?-cell failure alone) leading to the development of T2DM in the setting of greater residual ?-cell function relative to those with non-obese T2DM. We also know that the “metabolic memory” exists, thus another reason for regaining glycemic control early on before much of ?-cell mass and function is lost. Sinai Hospital, Toronto on a study that aims to preserve pancreatic ?-cell function and achieve remission of diabetes through the short-term use of intensive insulin therapy. Our current culture and healthcare set-up thus produces “psychological insulin resistance” as patients and health care providers fear insulin initiation (6, 7).
The loss of the first phase and a decrease in the second phase of prandial insulin secretion is one of the earliest signs of defective ?-cell function as impaired glucose tolerance (IGT). However, persistently elevated free fatty acids and chronic hyperglycemia may contribute to progressive ?-cell failure (?-cell lipotoxicity) in patients with diabetes or those predisposed to developing diabetes. This reflects late-phase insulin secretion and was the strongest predictors of the improvement in ?–cell function following short-term IIT (16).
Overall, the study population experienced an increase in ?–cell function, with a third of participants improving ?–cell function by at least ?25%. In Kramer et al.’s meta-analyses (18), in patients with newly diagnosed T2DM, short-term IIT is associated with improvement in ?-cell function and IR. Oxidative stress and pancreatic inflammation caused by hyperglycemia is likely involved in ?-cell dysfunction as well. These participants also had greater changes in reduction of fasting glucose, A1C, ALT, AST and IR.
Factors that emerge during treatment: the faster achievement of glycemic targets and lower requirements for exogenous insulin. Stage 3 is transient unstable early decompensation:  glucose levels rise rapidly to the diabetic levels of stage 4. Medications such as some sulfonylureas and glucocorticoids may also promote the progression of ?-cell dysfunction or even possibly ?-cell death.
Additionally, the decline in IR and improved lipid profile without use of lipid-adjusting agents were also indicators of the reduction in glucotoxicity. At baseline, the third of participants with greatest improvement in ?–cell function had higher fasting glucose, higher A1C, and lower ?–cell function.
Baseline characteristics associated with glycemic remission were increased BMI and decreased fasting plasma glucose, as well as low post-intensive insulin therapy fasting plasma glucose and post-challenge glucose.
The increase in glucose concentration likely worsens glucotoxic effects on ?-cells leading to less efficient insulin secretion.
All treatment groups achieved high rates of initial euglycemia but the insulin therapy group was associated with significantly higher rates of remission and preservation of first-phase insulin secretion after 1 year.
Thus, their poor glycemic control at baseline may be reflective of more pronounced effects of glucotoxicity resulting in the greatest improvements in ? –cell function from IIT.
The baseline factors indentified as predictors of remission are possibly indicative of increased underlying residual ?–cell function (eg, after elimination of the glucotoxic effects of hyperglycemia). Stage 4 is stable decompensation: there is ?-cell mass reduction and more severe ?-cell dysfunction and rapid increase in glucose levels.
This suggests that more profound ?–cell rest by IIT is likely to go beyond glucose-lowering effects and could possibly have extended benefits such as anti-inflammatory and anti-apoptosis effects. Upon further analyses, the reversibility of ?–cell dysfunction was achieved in only those participants where IIT yielded an improvement in IR.
The high BMI could be a marker for increased ?–cell mass available for recovery as results from post-mortem studies show that obesity increases ?–cell mass in both diabetic and non-diabetic individuals. Those that are apparent immediately after treatment: greater improvement in ?-cell function from that which was observed at baseline has been a consistent predictor of the response to short-term insulin therapy in previous studies. Thus, early intensive glycemic control by IIT as compared to OAD, could provide a more beneficial type of ?–cell rest and reduce excessive secretory demands on damaged ?–cells by affecting the metabolic memory, impeding the progression from metabolic abnormalities to irreversible cellular alterations.
Hence, decline in IR may be a key determinant of improvement of ?–cell function in response to short-term IIT, suggesting a fundamental contribution of IR to the reversible component of ?–cell dysfunction in early T2DM. These effects might further alter the natural history of diabetes and prevent or reduce the development and progression of diabetes-related complications. This will help to identify which patients are most likely to respond to IIT and the pathophysiology underlying this effect. For example, people with T2DM can move from stage 4 to stage 1 or 2, for example, individuals with T2DM who undergo gastric reduction surgery.
In order to stop the progression of T2DM from one stage to next it is necessary to minimize ?-cell loss and preserve remaining ?-cell function.



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