Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes
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TLDR
It is believed that the most important consideration is to select antidiabetes agents that correct specific pathophysiologic disturbances present in T2DM and that have complementary mechanisms of action.Abstract:
Two general approaches to the treatment of type 2 diabetes mellitus (T2DM) have been advocated. 1 ) A “guideline” approach that advocates sequential addition of antidiabetes agents with “more established use” (1); this approach more appropriately should be called the “treat to failure” approach, and deficiencies with this approach have been discussed (2). And 2 ) a “pathophysiologic” approach using initial combination therapy with agents known to correct established pathophysiologic defects in T2DM (3). Within the pathophysiologic approach, choice of antidiabetes agents should take into account the patient’s general health status and associated medical disorders. This individualized approach, which we refer to as the ABCD(E) of diabetes treatment (4), has been incorporated into the updated American Diabetes Association (ADA) guidelines (5).
Even though physicians must be cognizant of these associated conditions (ABCDE) when initiating therapy in newly diagnosed T2DM patients, we believe that the most important consideration is to select antidiabetes agents that correct specific pathophysiologic disturbances present in T2DM and that have complementary mechanisms of action. Although it has been argued that the pathogenesis of T2DM differs in different ethnic groups (6), evidence to support this is weak. Although the relative contributions of β-cell failure and insulin resistance to development of glucose intolerance may differ in different ethnic groups (6), the core defects of insulin resistance in muscle/liver/adipocytes and progressive β-cell failure (3) are present in virtually all T2DM patients and must be treated aggressively to prevent the relentless rise in HbA1c that is characteristic of T2DM.
In subsequent sections, we provide a review of the natural history of T2DM, specific pathophysiologic abnormalities responsible for T2DM, currently …read more
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Journal ArticleDOI
Type 2 diabetes mellitus.
Ralph A. DeFronzo,Ele Ferrannini,Leif Groop,Robert R. Henry,William H. Herman,Jens J. Holst,Frank B. Hu,C. Ronald Kahn,Itamar Raz,Gerald I. Shulman,Donald C. Simonson,Marcia A. Testa,Ram Weiss +12 more
TL;DR: The greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications.
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Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial
TL;DR: Exenatide plus dapagliflozin was significantly superior to either drug alone for all secondary efficacy endpoints, with greater reductions in fasting plasma and postprandial glucose, more patients with an HbA1c less than 7·0%.
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Mechanisms of Diabetes-Induced Liver Damage: The role of oxidative stress and inflammation
TL;DR: This review summarises the biochemical, histological and macromolecular changes that contribute to oxidative liver damage among diabetic individuals.
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The Time Is Right for a New Classification System for Diabetes: Rationale and Implications of the β-Cell–Centric Classification Schema
Stanley Schwartz,Solomon Epstein,Barbara E. Corkey,Struan F.A. Grant,James R. Gavin,Richard B. Aguilar +5 more
TL;DR: An urgent call is issued for the review of the current DM classification system toward the consensus on a new, more useful system that obviates the inherent and unintended confusions.
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Long-term Sustainability of Diabetes Prevention Approaches: A Systematic Review and Meta-analysis of Randomized Clinical Trials.
J. Sonya Haw,Karla I. Galaviz,Audrey Straus,Alysse J. Kowalski,Matthew J. Magee,Mary Beth Weber,Jingkai Wei,K.M. Venkat Narayan,Mohammed K. Ali +8 more
TL;DR: In adults at risk for diabetes, LSM and medications (weight loss and insulin-sensitizing agents) successfully reduced diabetes incidence, suggesting that interventions to preserve effects are needed.
References
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Journal ArticleDOI
Maximum Tubular Reabsorption Capacity for Glucose and Renal Hemodynamics during Rapid Hypertonic Glucose Infusion in Normal and Diabetic Subjects
TL;DR: It is demonstrated that the maximum tubular reabsorption capacity for glucose (Tmo) is significantly increased in young patients with diabetes of short duration and GFR is also significantlyIncreased in diabetics.
Journal ArticleDOI
IS THE COMBINATION OF SULFONYLUREAS AND METFORMIN ASSOCIATED WITH AN INCREASED RISK OF CARDIOVASCULAR DISEASE OR ALL-CAUSE MORTALITY? A Meta-Analysis of Observational Studies
TL;DR: The combination therapy of metformin and sulfonylurea significantly increased the RR of the composite end point of cardiovascular hospitalization or mortality irrespective of the reference group, however, there were no significant effects of this combination therapy on either CVD mortality or all-cause mortality alone.
Journal ArticleDOI
Effects of Rosiglitazone, Glyburide, and Metformin on β-Cell Function and Insulin Sensitivity in ADOPT
Steven E. Kahn,John M. Lachin,Bernard Zinman,Steven M. Haffner,R. Paul Aftring,Gitanjali Paul,Barbara G. Kravitz,William H. Herman,Giancarlo Viberti,Rury R. Holman +9 more
TL;DR: The favorable combined changes in β-cell function and insulin sensitivity over time with rosiglitazone appear to be responsible for its superior glycemic durability over metformin and glyburide as initial monotherapy in type 2 diabetes.
Journal ArticleDOI
Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005.
TL;DR: The incretin mimetics, administered by sc injection, have demonstrated lasting improvement in HbA1c in patients insufficiently treated with conventional oral therapy, and their use has been associated with steady weight loss for up to 2 years.
Journal ArticleDOI
Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study
Bernard Zinman,Bernard Zinman,Stewart B. Harris,Jan Neuman,Hertzel C. Gerstein,Ravi Retnakaran,Janet Raboud,Janet Raboud,Ying Qi,Anthony J. Hanley +9 more
TL;DR: Low-dose combination therapy with rosiglitazone and metformin was highly effective in prevention of type 2 diabetes in patients with impaired glucose tolerance, with little effect on the clinically relevant adverse events of these two drugs.
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