“Draft:Diabetes Remission Clinical Trial”的意思、由来-开放百科全书

{{COI|date=September 2018}}{{cleanup-reorganize|date=September 2018}}Diabetes Remission Clinical Trial (DiRECT)

Until recently, type 2 diabetes was considered a permanent, inevitably progressive, cruelly disabling, disease. Patients were often not made fully aware of its devastating and life-shortening consequences. The concept of remission of diabetes is new, and it brings many major benefits to patients, to their families, and to healthcare services.^[1]

DiRECT is the largest research study ever supported by the charity Diabetes UK, and is considered a landmark trial.^[2] It was the first research study ever to attempt to halt and reverse the disease-process of type 2 diabetes, for overweight people with type 2 diabetes to achieve remission without the need for drugs or surgery.

DiRECT is led by Professor Mike Lean at the University of Glasgow, with Professor Roy Taylor at Newcastle University, following separate successful pilot research at both centres. The NHS “sponsor” of DiRECT is NHS Greater Glasgow and Clyde.^[3]

The results from just over 300 patients in DiRECT showed that almost half of all who attempted the intervention, at their own primary care surgeries, were no longer diabetic after 12 months, and almost 9/10 were no longer diabetic if they lost over 15 kg (2 stones). About half of those on antihypertensive drugs were able to stop them completely.^[4]

DiRECT used an intensive diet and lifestyle programme called Counterweight-Plus, which includes trained professional support with a nutritionally complete formula diet, and then a structured programme for Food Reintroduction, and long-term Weight Loss Maintenance. Counterweight-Plus has been extensively tested, and reliably leads to maintained weight losses of 15 kg or more if people adhere to the programme. As well as remission of diabetes in DiRECT, Counterweight-Plus led to improvements in cholesterol and blood pressure. Half of the patients with high blood pressures before the study were able to stop their antihypertensive drugs. The Counterweight-Plus intervention also resulted in significant improvement in overall Quality of Life.^[4]

The DiRECT study includes detailed analysis of the mechanisms behind type 2 diabetes and its remission. The results confirmed earlier suggestions that the root cause of type 2 diabetes is excess body fat, and specifically fat accumulation in vital organs (liver and pancreas), which is associated with a large waist circumference. This ‘ectopic’ fat accumulation interferes with the functions of the liver to increase glucose release into the blood stream, and pancreas to impair insulin production. These two factors produce type 2 diabetes and all its disabling complications.^[5]

Type 2 diabetes was previously thought to be a permanent and progressive disease, but the DiRECT trial has proved that it is not permanent if action is taken early enough to shed a significant amount of weight. At present the only programme which has evidence for achieving sustained remission of diabetes is Counterweight-Plus. Bariatric surgery can produce non-diabetic blood tests, but the treatment (surgery) must continue and adverse events are common.^[6] Other weight control methods such as meal replacements do not have evidence that they can generate the necessary sustained weight loss in people with type 2 diabetes, who usually fail to lose as much weight as non-diabetic people.^[7] Prevention of weight regain is a major problem, requiring greater research investment in the future.^[8]

Type 2 diabetes affects between 1 in 10 and 1 in 20 (10%-20%) of all adults in UK, Europe and US, and a much greater proportion (up to 1 in 3, 30-40%) of people with Asian origins.^[9]^[10] It is the leading cause of blindness, amputations and kidney failure requiring dialysis.^[11] It accelerates heart disease and dementia.^[12] Type 2 diabetes treatments and complications account for about 10% of total healthcare budgets,^[13] but anti-diabetes drug treatments (approved to lower HbA1c) only delay or reduce the complications.

The top research priority of people with diabetes is to find a cure or method to reverse type 2 diabetes.^[14] DiRECT has shown that remission of type 2 diabetes is now achievable for most patients, and remission should now be the primary target for routine diabetes care, using an evidence-based long-term management programme.^[15]

The DiRECT trial continues until 2020, with funding from Diabetes UK to collect results up to 4 years after weight loss. Updates and new results are posted on www.directclinicaltrial.org.uk

References

1. ^McCombie, L., Leslie, W., Taylor, R., Kennon, B., Sattar, N. and Lean, M.E.J. (2017) Beating type 2 diabetes into remission. British Medical Journal, 358, j4030. (doi:10.1136/bmj.j4030)
2. ^{{cite web|url=https://www.diabetes.org.uk/research/research-round-up/research-spotlight/research-spotlight-low-calorie-liquid-diet|title=Research spotlight – putting Type 2 diabetes into remission|website=Diabetes UK|accessdate=14 September 2018}}
3. ^Leslie WS, Ford I, Sattar N, Hollingsworth KG, Adamson A, Sniehotta FF, McCombie L, Brosnahan, N, Ross H, Mathers JC, Peters C, Thom G, Barnes A, Kean S, McIlvenns Y, RodriguesA, Rehackova L, Zhyzhneuskaya S, Taylor R, Lean MEJ. The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial. BMC Fam Pract.2016 Feb 16;17:20. doi: 10.1186/s12875-016-0406-2
4. ^¹Lean MEJ, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamsson AJ, Sniehotta FF,Mathers JC, Ross HM, McIlvenna Y, Stefanetti R, Trenell M, Welsh P, Kean S, Ford I, McConnachie A,Sattar N, Taylor R. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018 Feb 10;391(10120):541-551. doi: 10.1016/S0140-6736(17)33102-1. Epub 2017 Dec 5
5. ^Taylor R, Al-Mrabeh, Zhyzhneuskaya S, Peters C,Barnes AC, Aribisala BS, Hollingworth KG, Mathers JC, Sattar N, Lean MEJ . Remission of Human Type 2 Diabetes Requires Decrease in Liver and Pancreas Fat Content but Is Dependent upon Capacity for β Cell Recovery. Cell Metab. 2018 Aug 2. pii: S1550-4131(18)30446-7. doi: 10.1016/j.cmet.2018.07.003. [Epub ahead of print]
6. ^Meier JJ, Butler AE, Galasso R, Butler PC. Hyperinsulinemic hypoglycemia after gastric bypass surgery is not accompanied by islet hyperplasia or increased beta-cell turnover. Diabetes Care. 2006 Jul;29(7):1554-9> 7. ^Leslie WS, Taylor R, Harris L, Lean MEJ. Weight losses with low-energy formula diets in obese patients with and without type 2 diabetes: systematic review and meta-analysis. Int J Obes (Lond). 2017 Jun;41(6):997. doi: 10.1038/ijo.2017.46. Epub 2017 Mar 14
8. ^Lean MEJ & Hankey CR. Keeping it off: the challenge of weight loss maintenance. Lancet Diabetes Endocrinol. 2018 Jan 19. pii: S2213-8587(17)30405-9. doi: 10.1016/S2213-8587(17)30405-9. [Epub ahead of print}
9. ^{{cite web|url=http://www.who.int/diabetes/global-report/en/|title=Global report on diabetes|website=World Health Organization|accessdate=14 September 2018}}
10. ^Guariquita L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014 Feb;103(2):137-49. doi: 10.1016/j.diabres.2013.11.002. Epub 2013 Dec 1
11. ^Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlogge AW,Malanda B. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018 Apr;138:271-281. doi: 10.1016/j.diabres.2018.02.023. Epub 2018 Feb 26
12. ^Biessels GJ, Strachan MV, Visseren FL, Kappelle LJ Whitmer RA. Dementia and cognitive decline in type 2 diabetes and pre-diabetic stages: towards targeted interventions. Lancet Diabetes Endocrinol. 2014 Mar;2(3):246-55. doi: 10.1016/S2213-8587(13)70088-3. Epub 2013 Oct 18
13. ^Hex N, Bartlett C, Wright D, Taylor M, Varley D. Estimating the current and future costs of Type 1 and Type 2 diabetes in the UK, including direct health costs and indirect societal and productivity costs. Diabet Med. 2012 Jul;29(7):855-62. doi: 10.1111/j.1464-5491.2012.03698
14. ^{{cite journal |vauthors=Finer S, Robb P, Cowan K, etal|date=2018|title=Setting the top 10 research priorities to improve the health of people with Type 2 diabetes: a Diabetes UK-James Lind Alliance Priority Setting Partnership. |journal=Diabet Med |volume=35 (7) |pages=862-870|url=http://qmro.qmul.ac.uk/xmlui/handle/123456789/42144}}
15. ^Lean MEJ, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamsson AJ, Sniehotta FF, Mathers JC, Ross HM, McIlvenna Y, Stefanetti R, Trenell M, Welsh P, Kean S, Ford I, McConnachie A, Sattar N, Taylor R. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018 Feb 10;391(10120):541-551. doi: 10.1016/S0140-6736(17)33102-1. Epub 2017 Dec 5