LIVER FAT SURROGATESUSED AS MARKERSALT Men in the top quarter (> 29 U⁄ l) of baseline ALT vs.those in bottomquarter (< 17 U⁄ l) had anadjusted odds ratio of 2.04 (95% CI 1.16–3.58) for incident diabetes in the West of ScotlandCoronary Prevention Study (WOSCOPS)Sattar N e al. Diabetes 2004; 53: 2855–2860.
ALT & INCIDENT DIABETESNewdiabetes>29 U/l => double risk of diabetes< 17 U/l17-21 U/l22 – 28 U/l0%1%2%3%4%5%0 1 2 3 4 5YearsSattar et al, Diabetes Nov 2004
LIVER FAT SURROGATESUSED AS MARKERSGGTBilirubinPAI -1tPA All have been implicated as the prediction markersSHBGFerritinCRP
INFLAMMATIONThe causality is not clearIntervention studies will serve as the litmus testSeveral molecules like CRP IL-6Have been implicated in the pathogenesis
INFLAMMATIONAND DIABETESSattar N. Biomarkers for diabetes prediction, pathogenesis or pharmacotherapy guidance? Past, present and future possibilities. Diabet Med. 2012 Jan;29(1):5-13.
FACTORS IMPLICATED BYEPIDEMIOLOGYAdiponectin Endogenous insulin sensitizer Increased adiponectin – increased all cause mortality- The “adiponectinparadox” More data neededVitamin D Deficiency supposed to cause diabetes Data weak Controversial
Combined Cardiovascular risk / Diabetes screening:Current cardiovascular risk assessment questions:Age, gender, prior CVD, family Hx CVD, smoking, ethnicity, social deprivation (post code)Simple measurements:Blood pressure, BMIADD HbA1c to non-fasting lipids, U&Es, LFTsLow risk:General adviceRescreen in 3 years ≥6.0 - 6.4%DiabetesHigh risk:Lifestyle advice, weight lossRescreen in 1 yearPreiss, Khunti, Sattar: (Diab Med Jan 2011)≥6.5%<6.0%
BIOMARKERS IN PREDICTIONOF INCIDENT DIABETESToo many to know!Salomaa V, Havulinna A, Saarela O, Zeller T, Jousilahti P, Jula A, Muenzel T, Aromaa A, Evans A, Kuulasmaa K, Blankenberg S.Thirty-one novel biomarkers as predictors for clinically incident diabetes. PLoS One. 2010 Apr 9;5(4):e10100.
BIOMARKERS – COMPLICATIONS /TREATMENT GUIDANCE?1. To better predict CVD & microvascular & other complications?2. Predict declining beta cell function/ progression to insulin?3. Help predict differential response to therapies?4. Combine with genetics to determine not only causal pathways (e.g. TGgenetics, and retinopathy risk) but also treatment responses(phenotype/genotype)
NOVEL BIOMARKERSPlasmin-α2-antiplasmin complex (PAP)*Fibrinogen*ApoAI#Retinal arteriolar tortuosity#*Nguyen TT, Alibrahim E, Islam FM, Klein R, Klein BE, Cotch MF, Shea S, Wong TY. Inflammatory, hemostatic, andother novel biomarkers for diabetic retinopathy: the multi-ethnic study of atherosclerosis. Diabetes Care. 2009Sep;32(9):1704-9.#Sasongko MB, Wong TY, Nguyen TT, Shaw JE, Jenkins AJ, Wang JJ. Novel versus traditional risk markers fordiabetic retinopathy. Diabetologia. 2012 Mar;55(3):666-70
DIABETIC RETINOPATHY- DOWE NEED MARKERS?Old New
TRADITIONAL VS NOVELBIOMARKERS“Only 50 % of the identified biomarkers were regarded valid due tomodest methodological quality and frequent lack of adjustment fortraditional risk factors. More rigorous evaluation of novel biomarkersis advocated to assess clinical applicability.”Validity of Biomarkers Predicting the Onset and the Progression ofNephropathy in Patients with Type 2 Diabetes: A Systematic ReviewMerel E. Hellemons 1*, Julia Kerschbaum 2*, Stephan J.L. Bakker 1, HannesNeuwirt 2, Bernd Mayer 3, Gert Mayer 2, Dick de Zeeuw 1 Hiddo J. LambersHeerspink 1, Michael Rudnicki 2
Plasma hsCRP, E-selectin, TPA, vWF and triglyceridessignificantly predicted onset or progression of nephropathy instudies combining normoalbuminuric and microalbuminuricpatients.Validity of Biomarkers Predicting the Onset and the Progression ofNephropathy in Patients with Type 2 Diabetes: A Systematic ReviewMerel E. Hellemons 1*, Julia Kerschbaum 2*, Stephan J.L. Bakker 1,Hannes Neuwirt 2, Bernd Mayer 3, Gert Mayer 2, Dick de Zeeuw 1 HiddoJ. Lambers Heerspink 1, Michael Rudnicki 2
UNMET NEEDSBiomarkers to predict the progressionto insulin therapyBiomarkers to predict differentialresponse to theapy