go here alt="Goldin" class="lazy lazy-hidden alignright size-full wp-image-716" width="220">As such, metformin is the most commonly used oral antihyperglycemic agent in the U.
However, based on the release of newer agents over the recent past, some have suggested that the Biology Empa Past Papers approach to disease management should be based upon identification of its etiology and correcting the underlying biological disturbances. That is, we should use interventions that normalize or at least ameliorate the recognized derangements in physiology that drive the clinical manifestation of disease, in this circumstance, hyperglycemia.
Thus, it is argued that therapeutic interventions that target glycemia but do not correct the underlying pathogenic disturbances are unlikely to result in a sustained benefit on the disease process.
F212 June 2010
In our field, there is an evolving debate regarding the suggested first step in diabetes management and a call for a new paradigm. Given the current controversy, we provide a Point-Counterpoint debate on this issue.
In the point narrative below that precedes the counterpoint narrative, Drs.
Abdul-Ghani and DeFronzo provide their argument that a treatment approach for type 2 diabetes based upon correcting the underlying pathophysiological abnormalities responsible for the development of hyperglycemia provides the best therapeutic strategy.
Such an approach requires a change in the recommendation for first-line therapy from metformin to a GLP-1 receptor Biology Empa Past Papers. In the counterpoint narrative that follows Drs.
Therapeutic interventions that simply target hyperglycemia but do not correct the underlying pathogenic disturbances are unlikely to result in a sustained reduction in HbA 1c.
Hyperglycemia is a manifestation of these eight pathophysiological abnormalities. Nonetheless, the current recommended approach in T2D management still focuses on lowering source plasma glucose concentration rather than correcting the underlying metabolic abnormalities that cause the hyperglycemia 2 — 4.
Therefore, it is not surprising that current therapeutic guidelines 2 — 4 do not result in a sustained HbA 1c reduction 5 — 8. Biology Empa Past Papers this Point-Counterpoint, we argue that it is time to apply the modern concepts of clinical practice to diabetes management and base therapy on Biology Empa Past Papers.
The etiology of T2D is complex and involves multiple pathophysiological disturbances involving multiple organs 1 Fig. Insulin resistance is also associated with multiple metabolic abnormalities, e. Each individual component of the insulin resistance syndrome, as well as the basic molecular etiology of the insulin resistance 25is causally related to the development of atherosclerotic cardiovascular disease CVD and contributes to the increased risk for CVD in T2D patients.
Further, T2D patients have elevated fasting plasma glucagon levels that fail to suppress normally after a meal and enhanced hepatic sensitivity to glucagon 2829in part due to resistance to GLP-1 2630 ; these pathophysiological abnormalities can be reversed with GLP-1 RA therapy 26 Recent evidence suggests that gut stimulation of GLP-1 secretion by the L cells is an important mechanism via which metformin suppresses hepatic glucose production 43 Thus, reducing CVD risk is a high priority in T2D management, and reduction in blood pressure and correction of diabetic dyslipidemia are essential components of diabetes management.
Numerous clinical trials have demonstrated that antidiabetes agents that reduce plasma glucose without altering other cardiovascular risk factors fail to reduce CVD risk in T2D patients. Conversely, antidiabetes medications that in addition to lowering the plasma glucose concentration also improve cardiovascular risk factors, e.
Thus, these agents should be favored over agents that lower plasma glucose but have no effect on cardiovascular risk factors or CVD, e. This suggests the GLP-1 RAs may have a direct beneficial action to slow the atherosclerotic process, independent of their effect to reduce glycemia and improve traditional cardiovascular risk factors Not all antidiabetes agents are equal in their ability to reduce cardiovascular risk.
GLP-1 RAs correct six members of the Ominous Octet, whereas the only known action of metformin is to inhibit hepatic glucose production 61 Fig. Contrary to common belief, metformin is not an insulin sensitizer in muscle or adipocytes 61 — 63 in the absence of weight loss, which is a frequent occurrence in patients treated with the biguanide Fig.
Consistent with this, following intravenous administration of 11 C-metformin, none of the biguanide can be detected in muscle Because the GLP-1 RAs cause significant weight loss, they also improve insulin sensitivity in muscle.
The major mechanism of action of metformin to reduce glycemia is inhibition of hepatic gluconeogenesis 6162 Fig. Effect of metformin on glycemic control, insulin secretion, and insulin sensitivity in T2D. The primary effect via which metformin reduces the HbA 1c in T2D is related to the suppression of hepatic glucose production HGP via inhibition of gluconeogenesis FPG, fasting plasma glucose. Effect of metformin on HbA 1c. Moreover, a beneficial effect on cardiovascular events was not observed in other clinical studies with metformin, i.
To the contrary, subjects receiving metformin in ADOPT experienced more cardiovascular events than subjects receiving glyburide, although this difference was not statistically significant.
This emphasizes the problem of interpreting results Biology Empa Past Papers studies that are read article underpowered to detect clinically significant differences in cardiac event rates. Further, and unlike those with metformin, the GI side effects usually are mild to moderate, waning over the first 4—6 weeks of initiating therapy. The percentage of patients who discontinue long-acting GLP-1 RAs because of GI side effects is significantly lower than that of metformin However, intermediate-acting metformin requires multiple daily dosing, whereas two long-acting GLP-1 RAs exenatide and dulaglutide are available as weekly injections and a third semaglutide is under review by the U.
Food and Drug Administration. A subcutaneously implanted osmotic mini pump that continuously delivers exenatide for 6 months is expected to be approved within the next year 69and an oral formulation of the GLP-1 RA semaglutide is in phase 3 trials 70 and is anticipated to be available within 3—4 years. Lastly, metformin is generic and inexpensive, whereas GLP-1 RAs are still under patent and, therefore, expensive.
Moreover, liraglutide Victoza is expected to become generic Biology Empa Past Papers the end ofand this should significantly reduce its cost. A cost-effective analysis is beyond the scope of this discussion, and the appropriate long-term, clinical, real-world studies to perform such an analysis are not available.
However, a recent cost analysis for the treatment of T2D patients in the U. It remains to be determined whether, on a long-term basis, the use of GLP-1 RAs, which in addition to causing a durable reduction in the plasma glucose concentration thereby decreasing microvascular complications also reduce cardiovascular events, will be cost-effective.
In summary, the currently available clinical and scientific evidence Table 2 is overwhelmingly in favor of the use of GLP-1 RAs over metformin as first-line therapy in newly diagnosed T2D patients. No other Biology Empa Past Papers conflicts of interest relevant to this article were reported. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
More information is available at http: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email Biology Empa Past Papers. Skip to main content. Diabetes Care Aug; more info 8: Pathophysiology of T2D The etiology of T2D is complex and involves multiple pathophysiological disturbances involving multiple organs 1 Fig.
View inline View popup. Figure 2 Not all antidiabetes agents are equal in their ability to reduce cardiovascular risk. Figure 3 Effect of metformin on glycemic control, insulin secretion, and insulin sensitivity in T2D.
Footnotes See accompanying article, p.
From the triumvirate to the ominous octet: Diabetes ; Management of hyperglycemia in type 2 diabetes, Diabetes Care ; Consensus statement of the American Association of Clinical Endocrinology and American College of Endocrinology on the comprehensive type 2 diabetes algorithm— executive summary. Endocr Pract ; Global Guideline for Type 2 Diabetes.
Brussels, BelgiumInternational Diabetes Federation, p. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy.
This page contains past papers for AQA A-Level Biology Units for GCE from to Below are all the AQA A Level Biology Question Papers and Mark Schemes available for download. Biology and Disease papers The variety of living organisms. BackgroundThe effects of empagliflozin, an inhibitor of sodium–glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in. Original Article. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. Bernard Zinman, M.D., Christoph Wanner, M.D., John M. . Animated Science News. Dear Users, It has been a busy year with many developments on the elearning front. I have been waiting .
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