Depiction of the elements of decision-making used to determine appropriate efforts to achieve glycaemic targets. Greater concerns about a particular domain are represented by increasing height of the ramp. Thus, characteristics/predicaments towards the left justify more stringent efforts to lower HbA1c, whereas those towards the right are compatible with less stringent efforts. Where possible, such decisions should be made in conjunction with the patient, reflecting his or her preferences, needs and values. This ‘scale’ is not designed to be applied rigidly but to be used as a broad construct to help guide clinical decisions. Adapted with permission from Ismail-Beigi et al [ref 20]
Fig. 2C should be considered when the goal is to minimize costs. This reflects prevailing costs in the North America and Europe in early 2012; costs of certain drugs may vary considerably from country to country and as generic formulations become available.
Fig. 2A should be considered when the goal is to avoid hypoglycemia. Note that "hidden" agents may obviously still be used when required, but additional care is needed to avoid adverse events. Here, the risk of hypoglycemia when using the hidden agents will be, in part, dependent on the baseline degree of hyperglycemia, the treatment target, and the adequacy of patient education.
Fig. 2B should be considered when the goal is to avoid weight gain. Note that "hidden" agents may obviously still be used when required, but additional care is needed to avoid adverse events. Here, the chances of weight gain when using the hidden agents will be mitigated by more rigorous adherence to dietary recommendations and optimal dosing.
In the VADT study, hypoglycaemia, together with HbA 1c levels, HDL levels, age and a history of prior events, was a major predictor of cardiovascular mortality Reference: Duckworth W ( VADT): results. 2008. Available from http:// webcasts.prous.com/netadmin/webcast_viewer/Preview.aspx?type=0&lid=3853, Accessed: 20 Oct 2009.
Hypoglycemic events may trigger inflammation by inducing the release of C-reactive protein (CRP), IL-6, and vascular endothelial growth factor (VEGF). Hypoglycemia also induces increased platelet and neutrophil activation. The sympathoadrenal response during hypoglycemia increases adrenaline secretion and may induce arrhythmias and increase cardiac workload. Underlying endothelial dysfunction leading to decreased vasodilation may also contribute to cardiovascular risk. Desouza CV et al. Hypoglycemia, Diabetes, and Cardiovascular Events. Diabetes Care. 2010; 33: 1389-1394.
Episodes of hypoglycemia, even asymptomatic episodes, impair defenses against subsequent hypoglycemia by causing hypoglycemia-associated autonomic failure (HAAF), the clinical syndromes of defective glucose counterregulation and hypoglycemia unawareness, and therefore a vicious cycle of recurrent hypoglycemia. The shift of the glycemic thresholds for sympathoadrenal responses to lower plasma glucose concentrations caused by recent antecedent hypoglycemia (or by sleep or prior exercise) could be the result of alterations in the peripheral afferent or efferent components of the autonomic nervous system or within the CNS. Cryer PE. Mechanisms of sympathoadrenal failure and hypoglycemia in diabetes. J. Clin. Invest. 2006;116:1470–1473
Model of ischemia-induced neovascularization in normal and high glucose. A, In the presence of normal glucose concentration, ischemia-stabilized HIF-1α forms heterodimers with ARNT which bind the coactivator p300. This complex binds to the hypoxia response element (HRE) and activates expression of genes required for neovascularization. B, High glucose–induced methylglyoxal (MG) modifies HIF-1α and p300, inhibiting complex binding to the HREs of genes required for neovascularization. Data are from Thangarajah et al34 and Ceradini et al.35 (Illustration Credit: Ben Smith/Cosmocyte).
• Almost everyone has heard the saying, “Ifyou want to keep a friend, never talk aboutreligion or politics.” In regard to thespecific management of type 2 diabetes,we can alter this phrase somewhat andsuggest, “If you want to keep a colleague,never talk about diabetes guidelines!”06:02:07DIABETES CARE, VOLUME 35, JUNE 2012 1201為了保有同事情誼不要討論糖尿病治療指引
•糖尿病的藥物治療策略1.依據證據醫學 ( 降血糖效果： A1C)來選藥2.依據病理生理學來矯正3.Patient-CenteredADA-EASD Position StatementManagement of Hyperglycemia in T2DM: APatient-Centered ApproachDiabetes Care April 2012
ADA consensus statementDCCT and UKPDS ： a strong correlationbetween mean A1C levels over time and thedevelopment and progression of retinopathy andnephropathy=> it is reasonable to judge and compare bloodglucose–lowering medications, as well ascombinations of such agents, primarily on thebasis of their capacity to decrease and maintainA1C levels and according to their safety, specificside effects, tolerability, ease of use, andexpense.Diabetes Care 32:193–203, 2009小血管病變的證據醫學：向 A1C 看齊
Pharmacology and Therapeutics 124 (2009) 113-138明日之星?明日之星?GLP-1 mimeticsDPP-4 inhibitor
KEY POINTS• Glycemic targets & BG-lowering therapies must beindividualized.• Diet, exercise, & education: foundation of any T2DMtherapy program• Unless contraindicated, metformin = optimal 1st-linedrug.• After metformin, data are limited.with 1-2 other oral / injectable agents is reasonable;minimize side effects.• Ultimately, many patients will require insulin therapyalone / in combination with other agents to maintain BGcontrol.• All treatment decisions should be made in conjunctionwith the patient (focus on preferences, needs & values.)• Comprehensive CV risk reduction - a major focus oftherapy.Diabetes Care, Diabetologia. 19 April 2012Combination therapy
Metformin + other OADs 的降血糖效果和低血糖風險Adapted from: Phung, et al. JAMA. 2010;303(14):1410–1418
AACE 2010Goals as priorities in the selection of medications• Inclusion of major classes of FDA-approved glycemicmedication, including incretin-based therapies• Minimizing risk and severity of hypoglycemia• Minimizing risk and magnitude of weight gain• Consideration of both fasting and postprandialglucose levels as end points• In many cases, delaying pharmacotherapy to allow for lifestylemodifications is inappropriate because these interventions are usually notadequate• Consideration of total cost of therapy to the individual andsociety at large, including costs related to medications, glucose monitoringrequirements, hypoglycemic events, drug-related adverse events, andtreatment of diabetes-associated complications• The major cost is related to the treatment of the complications of diabetes. Webelieve that identification of the safest and most efficacious agents is essential.
• Age: Older adults– Reduced life expectancy– Higher CVD burden– Reduced GFR– At risk for adverse events from polypharmacy– More likely to be compromised fromhypoglycemiaLess ambitious targetHbA1c <7.5–8.0% if tighter targets not easily achievedFocus on drug safetyLess ambitious targetHbA1c <7.5–8.0% if tighter targets not easily achievedFocus on drug safety
老人有沒有效？a pooled analysis of five monotherapy trials comparing the effects of 24 weeksof vildagliptin treatment in younger (<65 years, n = 1231) and older (>65 years, n= 238) patientsDiabetes Obes Metab. 2011;13:55–64.
老人安不安全？SYE-adj, subject year exposure-adjustedHosp Pract (Minneap). 2011 Feb;39(1):7-21.