Table 1.

Biomarkers used in relation to T2DM

Biomarker	Target	Change in T2DM	Advantages	Disadvantages	Examples of BIPED* classification
HbA1C	Blood glucose	Elevated	Easy and fast to measure.		B, D:
			No restrictions prior to measurement.		Used as the Gold standard for diagnosis and monitoring of T2DM [29]
					E: HbA1C↓
					Sulphonylureas+ Rosaglitazone [53]
					Prioglitazone [54]
					Balaglitazone and Pioglitazone [55]
					Liraglutide and Sitagliptin [56]
					DDP-IV inhibitor LC 15–0444 [57]
Fasting plasma glucose (FPG)	Blood glucose	Elevated	Easy and fast to measure.	Require patients to be fasting prior to sampling	B, D:
					Used in the diagnosis and monitoring of T2DM [29]
					E: FPG ↓
					Sulphonylureas+ Rosaglitazone [53]
					Prioglitazone [54]
					Balaglitazone and Pioglitazone [55]
					Liraglutide and Sitagliptin [56]
					DDP-IV inhibitor LC 15–0444 [57]
Oral glucose tolerance test (OGTT) or Post-prandial glucose	Blood glucose clearance	Glucose clearance: Impaired	OGTT: Accurate assessment of functional glucose clearance by liver or peripheral tissues	Two hour test.	B, D:
					Used in the diagnosis and monitoring of T2DM [29]
		Post prandial glucose: Elevated	Post-prandial glucose: A less time-consuming method to assess glucose clearance than OGTT	Time consuming test for the patient.	E: Improved OGTT
					Prioglitazone [54]
					E: Post prandial glucose ↓
					Balaglitazone and Pioglitazone [55]
Pro-insulin	Β-cell stress/dysfunction	Elevated	Only current marker to assess β-cell dysfunction	Usually combined with additional tests: Fasting insulin, C-peptide	E: pro-insulin ↓
Split pro-insulin			Proinsulin not directly influenced by therapeutic injections of insulin		Exenatide [58]
Pro-insulin/Insulin ratio					E: Split pro-insulin ↓
					Prioglitazone [54]
					E: Split pro-insulin →
					Gliclazide [54]
					E: pro-insulin/insulin ratio ↓
					Liraglutide and Sitagliptin [56]
					Exenatide [58]
Fasting Insulin	Β-cell functionality	Elevated in early stages of disease development.	Short half life of insulin	Fasting insulin levels changes with the stages of pathogenesis of T2DM	E: Fasting Insulin ↑
		Decreased in late stages of T2DM		Injections with insulin is used as treatment in T2DM	Gliclazide [54]
					Chlorpropamide [59]
					Glibenclamide [59]
					Insulin [59]
					E: Fasting Insulin →
					Exenatide [58]
					Liraglutide and Sitagliptin [56]
					E: Fasting Insulin ↓
					Sulphonylureas+ Rosaglitazone [53]
					Prioglitazone [54]
					Metformin [59]
C-peptide	Total insulin secretion	Elevated in early stages of disease development.	Half life: C-peptide		E: C-peptide ↓
		Decreased in late stages of T2DM	> Insulin. Improved assessment of total insulin secretion		Sulphonylureas+Rosaglitazone [53]
			C-peptide not directly influenced by therapeutic injections of insulin		Prioglitazone [54]
					DDP-IV inhibitor LC 15–0444 [57]
					E: C-peptide ↑
					Liraglutide and Sitagliptin [56]
					Gliclazide [54]

*BIPED (Burden of disease, Investigative, Prognostic, Efficacy of intervention, Diagnostic).