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Content
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Diabetes ~ equivalent to MI
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Dia 3
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Blood pressure and vascular risk in diabetes Best evidence: 2000
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Blood pressure: best evidence 2009
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All-cause mortality
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Dia 7
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Population in ACCORD
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Intensive BP lowering (<120) versus standard BP treatment (<140)
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Intensive BP lowering (<120) is not better than standard BP (<140)
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Intensive BP lowering (<120) is not better than standard BP (<140)
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Aspirin in diabetes
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Belch J et al. BMJ 2008; 337:1030-44.
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Role of glucose in CV-disease
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Dia 15
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Glucose control in ACCORD
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Effect of intensive glucose regulation on major cardiovascular events
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UK General Practice Research Base
1986 –2008
Twee cohorten:
intensivering van orale medicatie
Intensivering naar insuline
Sterfte versus HbA1c decilen
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Survival versus HbA1c (oral treatment)
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Survival versus HbA1c (insulin treatment)
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Atherosclerosis Risk in Communities
(ARIC) study
Populatie-based sample 11,092 persons
No history of diabetes or cardiovascular disease
HbA1c measured in whole blood samples 1990-1992
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Higher HbA1c more CV-disease
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Higher HbA1c more stroke
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Holman R ea. N Engl J Med 2008;359:1577-89.
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Holman R ea. N Engl J Med 2008;359:1577-89.
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Interpretation
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Dia 27
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galega
officinalis
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Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy
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Metformin: evidence and pitfalls
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SU-derivatives
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Pioglitazone versus gliclazide added to metformin
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Time to treatment failure
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Thiazolidine-diones
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Dia 35
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Fracture risk in ADOPT
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Thiazolidine-diones
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Alpha-glucosidase inhibitors
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Diabetes Market Forecast to 2013
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The
incretin concept
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Nauck MA ea. JCEM 1986; 63:492
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Nauck MA ea. JCEM 1986; 63:492
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Incretin effect
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The incretin effect
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“The incretins”
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Incretins (GLP-1 and GIP) Regulate Glucose Homeostasis Through Effects on Islet Cell Function
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After release incretins are rapidly inactivated
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GLP-1 is Rapidly Degraded by the DPP-4 enzyme
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Degradation of incretins can be decreased by inhibition of the DPP-4 enzyme
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Effect of sitagliptin on top of metformin
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Vildagliptin Add-on to Metformin
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Dia 52
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DPP-4 remmers
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When to use incretins?
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Dia 55
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Effects of GLP-1
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General Prescribing Considerations:How It Is Supplied
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Effect of Exenatide on HbA1c (30 Weeks)
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Effect of Exenatide on Body Weight
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Adverse Events
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Insulin compared to GLP-1 analogueChange in HbA1c compared to baseline
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Insulin compared to GLP-1 analogueEffect on weight
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Samenvatting GLP-1 analogen
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Approach after combination therapy
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Dia 65
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Shah ND, et al. NEJM 2010; 363:2081-4.
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DeSouza C ea. Nat Rev Drug Discov 2009; 8:361-7.
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FDA guidance on CV outcome trials
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MACE analysis: Major Adverse Cardiovascular Events
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Best JH et al. Diabetes Care 2010; on line
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CV outcome trials investigating incretin based therapies
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Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy
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