This document discusses biomarkers in diabetes, including:
1. Biomarkers can help improve understanding of disease processes, predict disease severity and complications, and monitor treatment efficacy.
2. Liver enzymes like ALT and GGT, inflammatory markers like CRP and IL-6, and adipokines like adiponectin have been implicated in diabetes pathogenesis.
3. Simple risk scores combining basic measures like HbA1c and lipids can effectively predict diabetes, though more research is still needed on novel biomarkers.
3. WHAT IS A BIOMARKER?
Objectively measured indicators or normal
or abnormal physiological processes of an
organism
4. WHAT SHOULD A BIOMARKER
DO?
Improve the understanding of a disease process
Predict disease severity / complication
Improve treatment targeting
Monitor treatment efficacy
6. BIOMARKERS AND DIABETES
PATHOGENESIS
Broadly reflect these putative mechanisms of diabetes development
Role of hepatic fat
Inflammation and diabetes
Association and causality
Adiponectin
Vitamin D
9. LIVER FAT SURROGATES
USED AS MARKERS
ALT
Men in the top quarter (> 29 U⁄ l) of baseline ALT vs.those in bottomquarter (< 17 U⁄ l) had an
adjusted odds ratio of 2.04 (95% CI 1.16–3.58) for incident diabetes in the West of Scotland
Coronary Prevention Study (WOSCOPS)
Sattar N e al. Diabetes 2004; 53: 2855–2860.
10. ALT & INCIDENT DIABETESNewdiabetes
>29 U/l => double risk of diabetes
< 17 U/l
17-21 U/l
22 – 28 U/l
0%
1%
2%
3%
4%
5%
0 1 2 3 4 5
Years
Sattar et al, Diabetes Nov 2004
11. LIVER FAT SURROGATES
USED AS MARKERS
GGT
Bilirubin
PAI -1
tPA All have been implicated as the prediction markers
SHBG
Ferritin
CRP
12. INFLAMMATION
The causality is not clear
Intervention studies will serve as the litmus test
Several molecules like
CRP
IL-6
Have been implicated in the pathogenesis
13. INFLAMMATION
AND DIABETES
Sattar N. Biomarkers for diabetes prediction, pathogenesis or pharmacotherapy guidance? Past, present and future possibilities. Diabet Med. 2012 Jan;29(1):5-13.
14. FACTORS IMPLICATED BY
EPIDEMIOLOGY
Adiponectin
Endogenous insulin sensitizer
Increased adiponectin – increased all cause mortality- The “adiponectin
paradox”
More data needed
Vitamin D
Deficiency supposed to cause diabetes
Data weak
Controversial
18. PRINCIPLES TO PONDER
No need of perfection
Simple risk scores can get us far
Need to combine CVD and diabetes risk screening
HbA1c enters the arena!
19. Simple risk score at booking:
i.e. no bloods AUROC 82%
HDL-c, t-PA added AUROC
(86%) & IDI
BUT CRP, adiponectin NO
predictive value
21. 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, BMI
ADD HbA1c to non-fasting lipids, U&Es, LFTs
Low risk:
General advice
Rescreen in 3 years ≥6.0 - 6.4%
Diabetes
High risk:
Lifestyle advice, weight loss
Rescreen in 1 year
Preiss, Khunti, Sattar: (Diab Med Jan 2011)
≥6.5%<6.0%
22. BIOMARKERS IN PREDICTION
OF INCIDENT DIABETES
Too 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.
24. 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. TG
genetics, and retinopathy risk) but also treatment responses
(phenotype/genotype)
30. NOVEL BIOMARKERS
Plasmin-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, and
other novel biomarkers for diabetic retinopathy: the multi-ethnic study of atherosclerosis. Diabetes Care. 2009
Sep;32(9):1704-9.
#Sasongko MB, Wong TY, Nguyen TT, Shaw JE, Jenkins AJ, Wang JJ. Novel versus traditional risk markers for
diabetic retinopathy. Diabetologia. 2012 Mar;55(3):666-70
35. TRADITIONAL VS NOVEL
BIOMARKERS
“Only 50 % of the identified biomarkers were regarded valid due to
modest methodological quality and frequent lack of adjustment for
traditional risk factors. More rigorous evaluation of novel biomarkers
is advocated to assess clinical applicability.”
Validity of Biomarkers Predicting the Onset and the Progression of
Nephropathy in Patients with Type 2 Diabetes: A Systematic Review
Merel E. Hellemons 1*, Julia Kerschbaum 2*, Stephan J.L. Bakker 1, Hannes
Neuwirt 2, Bernd Mayer 3, Gert Mayer 2, Dick de Zeeuw 1 Hiddo J. Lambers
Heerspink 1, Michael Rudnicki 2
36. Plasma hsCRP, E-selectin, TPA, vWF and triglycerides
significantly predicted onset or progression of nephropathy in
studies combining normoalbuminuric and microalbuminuric
patients.
Validity of Biomarkers Predicting the Onset and the Progression of
Nephropathy in Patients with Type 2 Diabetes: A Systematic Review
Merel E. Hellemons 1*, Julia Kerschbaum 2*, Stephan J.L. Bakker 1,
Hannes Neuwirt 2, Bernd Mayer 3, Gert Mayer 2, Dick de Zeeuw 1 Hiddo
J. Lambers Heerspink 1, Michael Rudnicki 2
37. UNMET NEEDS
Biomarkers to predict the progression
to insulin therapy
Biomarkers to predict differential
response to theapy