Get Permission
Rev Diabet Stud, 2011, 8(3):432-440 DOI 10.1900/RDS.2011.8.432

Metabolic Memory and Individual Treatment Aims in Type 2 Diabetes – Outcome-Lessons Learned from Large Clinical Trials

Cristina Bianchi, Stefano Del Prato

Department of Endocrinology and Metabolism, Section of Diabetes and Metabolic Diseases, University of Pisa, Italy
Address correspondence to: Stefano Del Prato, e-mail:

Manuscript submitted October 26, 2011; accepted October 30, 2011.

Keywords: antihyperglycemic therapy, cardiovascular risk, glycemic control, glycemic legacy, macrovascular, microvascular complication, type 2 diabetes, UKPDS


Reducing the burden of long-term complications in type 2 diabetic patients remains a major task, and represents a huge challenge. Whilst tight glycemic control has been shown to reduce the risk of microvascular complications, controversy remains regarding the benefit of intensive treatment in relation to the prevention of cardiovascular events. Recent large trials (including ACCORD, ADVANCE, and VADT) were unable to show a significant impact of glycemic control on cardiovascular events. Also, it has been argued that these trials included patients with a long duration of the disease, and with previous unsatisfactory glycemic control. Chronic exposure to hyperglycemia may cause a kind of negative metabolic memory, and thereby reduce the potential impact of good glycemic control. This concept has been corroborated by the UKPDS which recruited only subjects with newly diagnosed diabetes and without prior cardiovascular events. In these patients, early achievement of glycemic control translated into a long-term reduction of the risk of micro- and macrovascular complications. This observation prompted the UKPDS investigators to propose a positive "glycemic legacy", supporting the need for early and appropriate treatment of hyperglycemia and associated metabolic disturbances. This should be feasible now through the selection of individual targets and personalized pharmacologic treatments. In doing so, the potential risks of intensive treatment might then be avoided.

Fulltext: HTML , PDF (302KB)

This article has been cited by other articles:

Efficacy and safety of repaglinide/metformin fixed-dose combination tablet in the treatment of type 2 diabetic patients

Wang X, Chen Q, Lyu X, Ye S, Jiang Z, Ni H, Wang W, Li K, Tang X, Yang J, Zhang X, Yu J, Zhang L, Zhang X, Zhong L, Li Q, Yang W

Chin J Endocrinol Metab 2014. 30(11):954-959

Insulin or surgery?

Blüher M

Chirurg 2014. 85(11):957-962

Differential transcriptional and posttranslational transcription factor 7-like regulation among nondiabetic individuals and type 2 diabetic patients

Pradas-Juni M, Nicod N, Fernandez-Rebollo E, Gomis R

Mol Endocrinol 2014. 28(9):1558-1570

The Role of MicroRNAs in Diabetic Complications - Special Emphasis on Wound Healing

Moura J, Borsheim E, Carvalho E

Genes (Basel) 2014. 5(4):926-956

Glycemic exposure, glycemic control, and metabolic karma in diabetic complications

Thomas MC

Adv Chronic Kidney Dis 2014. 21(3):311-317

Association among subclinical hypothyroidism, TSH levels and microvascular complications in Type 2 diabetic patients

Gao F, Poulle NP, Zafar MI, Shafqat RA

IOSR J Dent Med Sci 2014. 13(3):1-6

10-year incidence of diabetes and associated risk factors in Greece: the ATTICA study (2002-2012)

Koloverou E, Panagiotakos DB, Pitsavos C, Chrysohoou C, Georgousopoulou EN, Pitaraki E, Metaxa V, Stefanadis C, ATTICA Study Group

Rev Diabet Stud 2014. 11(2):181-189

Impact of bariatric surgeries on diabetes outcomes

Muscelli E, Muscelli Alecrim H

Rev Soc Bras Clin Med 2014. 12(2):1-11

Antiglycation Activity of Iridoids and Their Food Sources

West BJ, Uwaya A, Isami F, Deng S, Nakajima S, Jensen CJ

Int J Food Sci 2014. 2014:276950

Role of metabolic surgery in less obese or non-obese subjects with type 2 diabetes: influence over cardiovascular events

Cohen R, Caravatto PP, Petry T, Cummings D

Curr Atheroscler Rep 2013. 15(10):355

The continuing need for drug development and clinical trials in type 2 diabetes and its complications: introduction to the RDS Special Issue

Raz I, Gallwitz B

Rev Diabet Stud 2011. 8(3):288-292