Is regression to normoglycaemia clinically important?
2012; Elsevier BV; Volume: 379; Issue: 9833 Linguagem: Inglês
10.1016/s0140-6736(12)60828-9
ISSN1474-547X
AutoresNatalia Yakubovich, Hertzel C. Gerstein,
Tópico(s)Diabetes Management and Research
ResumoImpaired fasting glucose, impaired glucose tolerance, and type 2 diabetes are metabolic conditions characterised by raised blood glucose concentrations that put people at risk of various serious health outcomes. These concentrations generally rise with time so that patients with impaired fasting glucose or glucose tolerance progress to diabetes, 1 Gerstein HC Santaguida P Raina P et al. Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies. Diabetes Res Clin Pract. 2007; 78: 305-312 Summary Full Text Full Text PDF PubMed Scopus (402) Google Scholar and patients with diabetes need progressively more complex regimens to manage glucose concentrations. Several large randomised controlled trials have shown that diabetes can be prevented or delayed in people with impaired fasting glucose or impaired glucose tolerance by diet, physical activity, and various drugs. Less well understood is the clinical significance of regression of these conditions to normoglycaemia, which has been noted in several trials 2 Perreault L Kahn SE Christophi CA et al. Regression from pre-diabetes to normal glucose regulation in the Diabetes Prevention Program. Diabetes Care. 2009; 32: 1583-1588 Crossref PubMed Scopus (129) Google Scholar , 3 Snehalatha C Mary S Selvam S et al. Changes in insulin secretion and insulin sensitivity in relation to the glycemic outcomes in subjects with impaired glucose tolerance in the Indian Diabetes Prevention Programme-1 (IDPP-1). Diabetes Care. 2009; 32: 1796-1801 Crossref PubMed Scopus (42) Google Scholar , 4 Ramachandran A Snehalatha C Mary S et al. Pioglitazone does not enhance the effectiveness of lifestyle modification in preventing conversion of impaired glucose tolerance to diabetes in Asian Indians: results of the Indian Diabetes Prevention Programme-2 (IDPP-2). Diabetologia. 2009; 52: 1019-1026 Crossref PubMed Scopus (67) Google Scholar , 5 DeFronzo RA Tripathy D Schwenke DC et al. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med. 2011; 364: 1104-1115 Crossref PubMed Scopus (546) Google Scholar , 6 Gerstein HC Yusuf S Bosch J et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006; 368: 1096-1105 Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar , 7 Bosch J Yusuf S Gerstein HC et al. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006; 355: 1551-1562 Crossref PubMed Scopus (652) Google Scholar , 8 Zinman B Harris SB Neuman J et al. Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Lancet. 2010; 376: 103-111 Summary Full Text Full Text PDF PubMed Scopus (173) Google Scholar , 9 Kawamori R Tajima N Iwamoto Y Kashiwagi A Shimamoto K Kaku K Voglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese individuals with impaired glucose tolerance. Lancet. 2009; 373: 1607-1614 Summary Full Text Full Text PDF PubMed Scopus (239) Google Scholar , 10 Chiasson JL Josse RG Gomis R Hanefeld M Karasik A Laakso M Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002; 359: 2072-2077 Summary Full Text Full Text PDF PubMed Scopus (2135) Google Scholar (table). Does regression predict a reduced risk of incident metabolic and vascular diseases, or does it simply reflect glucose fluctuations over time? TableRisk of regression to normoglycaemia in people with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both N Population Length (years) Regression in controls (%) Active treatment Risk of regression* Unless otherwise noted, relative risk of regression to normoglycaemia was calculated from reported proportions of patients achieving normoglycaemia in treatment groups. (95% CI) DPP 2 Perreault L Kahn SE Christophi CA et al. Regression from pre-diabetes to normal glucose regulation in the Diabetes Prevention Program. Diabetes Care. 2009; 32: 1583-1588 Crossref PubMed Scopus (129) Google Scholar † Normoglycaemia was defined on basis of oral glucose tolerance test; fasting plasma glucose cutoffs varied between studies. 2528 IFG+IGT 3 NA LifestyleMetformin 2·05 (1·66–2·53)1·25 (0·99–1·58) Indian DPP-1 3 Snehalatha C Mary S Selvam S et al. Changes in insulin secretion and insulin sensitivity in relation to the glycemic outcomes in subjects with impaired glucose tolerance in the Indian Diabetes Prevention Programme-1 (IDPP-1). Diabetes Care. 2009; 32: 1796-1801 Crossref PubMed Scopus (42) Google Scholar 531 IGT 2·5 24·1% LifestyleMetforminLifestyle+metformin 1·48 (0·99–2·22)1·27 (0·85–1·89)1·31 (0·87–1·95) Indian DPP-2 4 Ramachandran A Snehalatha C Mary S et al. Pioglitazone does not enhance the effectiveness of lifestyle modification in preventing conversion of impaired glucose tolerance to diabetes in Asian Indians: results of the Indian Diabetes Prevention Programme-2 (IDPP-2). Diabetologia. 2009; 52: 1019-1026 Crossref PubMed Scopus (67) Google Scholar 407 IGT 3 32·3% Lifestyle+pioglitazone 1·27 (0·98–1·65) ACT NOW 5 DeFronzo RA Tripathy D Schwenke DC et al. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med. 2011; 364: 1104-1115 Crossref PubMed Scopus (546) Google Scholar † Normoglycaemia was defined on basis of oral glucose tolerance test; fasting plasma glucose cutoffs varied between studies. 602 IGT 2·4 28% Pioglitazone 1·71 (1·33–2·19) DREAM 6 Gerstein HC Yusuf S Bosch J et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006; 368: 1096-1105 Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar , 7 Bosch J Yusuf S Gerstein HC et al. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006; 355: 1551-1562 Crossref PubMed Scopus (652) Google Scholar † Normoglycaemia was defined on basis of oral glucose tolerance test; fasting plasma glucose cutoffs varied between studies. 5269 IFG+/–IGT 3 30·3%38·2% RosiglitazoneRamipril 1·71 (1·57–1·87) ‡ Hazard ratio of regression to normoglycaemia was provided in publication. 1·16 (1·07–1·27) ‡ Hazard ratio of regression to normoglycaemia was provided in publication. CANOE 8 Zinman B Harris SB Neuman J et al. Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Lancet. 2010; 376: 103-111 Summary Full Text Full Text PDF PubMed Scopus (173) Google Scholar † Normoglycaemia was defined on basis of oral glucose tolerance test; fasting plasma glucose cutoffs varied between studies. 207 IGT 3·9 53·1% Rosiglitazone+metformin 1·50 (1·21–1·86) Kawamori et al 9 Kawamori R Tajima N Iwamoto Y Kashiwagi A Shimamoto K Kaku K Voglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese individuals with impaired glucose tolerance. Lancet. 2009; 373: 1607-1614 Summary Full Text Full Text PDF PubMed Scopus (239) Google Scholar † Normoglycaemia was defined on basis of oral glucose tolerance test; fasting plasma glucose cutoffs varied between studies. 1780 IGT 0·9 51·5% Voglibose 1·54 (1·36–1·75) ‡ Hazard ratio of regression to normoglycaemia was provided in publication. STOP-NIDDM 10 Chiasson JL Josse RG Gomis R Hanefeld M Karasik A Laakso M Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002; 359: 2072-2077 Summary Full Text Full Text PDF PubMed Scopus (2135) Google Scholar 1429 IFG+IGT 3·3 31% Acarbose 1·14 (0·98–1·33) NA=not available. * Unless otherwise noted, relative risk of regression to normoglycaemia was calculated from reported proportions of patients achieving normoglycaemia in treatment groups. † Normoglycaemia was defined on basis of oral glucose tolerance test; fasting plasma glucose cutoffs varied between studies. ‡ Hazard ratio of regression to normoglycaemia was provided in publication. Open table in a new tab NA=not available. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes StudyWe conclude that prediabetes is a high-risk state for diabetes, especially in patients who remain with prediabetes despite intensive lifestyle intervention. Reversion to normal glucose regulation, even if transient, is associated with a significantly reduced risk of future diabetes independent of previous treatment group. Full-Text PDF
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