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Early weight loss following T2DM diagnosis – does the body remember?

8th June 2019, Dr Chee L Khoo

The majority of patients with type 2 diabetes (T2DM) are diagnosed and managed in primary in the early years. We know from the UKPDS that early tight glycaemic control have enduring legacy effects on cardiovascular morbidity and mortality. We also know from the DiRECT trials that significant weight loss when the diabetes duration is short can lead to diabetes remission (1,2). What about weight loss early in the diabetes disease? Does that translate to improvement in cardiovascular outcomes?

We always assume that lifestyle measures of decreased caloric intake and moderate intensity exercises is key to weight loss and thence, improvement in cardiovascular health. The evidence is sparse and conflicting. Many studies have demonstrated that moderate weight loss is associated with reduction in cardiovascular mortality (3). Further, the Swedish Obese Subjects (SOS) study 5 showed reduced rates of cardiovascular events during a mean follow-up of 13.3 years among patients with type 2 diabetes who had undergone bariatric surgery (4). However, the study was not randomised, and the results achieved through surgery cannot be generalized to other methods of weight loss.

However, the Look Ahead trial found that an intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes (5). In fact, the trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years.

We know that early glycaemic control may result in a legacy effect as demonstrated in the UKPDS (6). Can weight loss early after the diagnosis of T2DM result in similar legacy effect for cardiovascular morbidity and mortality? The Diabetes Care in General Practice trial of people with a new diagnosis of diabetes showed no association between 13-year CVD incidence and weight loss achieved through a 6-year intensive intervention [7]. The Retrospective Study of Cardiovascular Events Related to the Use of Glucose-Lowering Drug Treatment in Primary Care (ROSE) cohort study of individuals in Swedish primary care (N = 8486) showed that weight loss in the 18 months following diabetes diagnosis had no protective association with CVD events during a median follow-up time of 4.6 years (8). So, where does that lead us?

The Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)–Cambridge trial had a fresh look at the association of weight change in the year following diabetes diagnosis and 10-year CVD and mortality incidence (9).  24,654 patients from 49 practices in England participated in a diabetes screening program between 2002-2006. 867 participants were diagnosed with T2DM and were cluster randomised to either intensive treatment or usual care (according to UK diabetes management guidelines).

Intensive treatment included more frequent consultations, provision of educational materials and GP-based academic-detailing sessions encouraging earlier use of medication to improve control of risk factors. The outcomes of interest were CVD events and all-cause mortality. The composite CVD outcome included cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, non-traumatic amputation, and revascularisation. They excluded deaths occurring in the year following the assessment of weight change, to reduce the likelihood that weight loss in our study was caused by disease.

Compared with participants who maintained weight, those who lost ≥5% body weight had lower HbA1c, diastolic BP and triacylglycerols at 1 year. At 5 years, these improvements were only apparent among those who had lost ≥10% weight. Losing ≥5% of body weight was associated with a lower hazard of 10-year CVD events compared with maintaining weight (HR 0.52). There were no associations between weight loss and all-cause mortality.

Sulfonylurea use was most common among participants who gained weight. Metformin use comprised the majority of glucose-lowering drug use in this cohort, reducing our concerns of bias related to differential effects of glucose lowering drugs on weight and CVD. Exclusion of participants who reported sulfonylurea use at 1 year did not change any associations.

Most patients diagnosed with T2DM are diagnosed in primary care these days. Moderate weight loss may yield substantial long-term CVD reduction and may be an achievable target in primary care.

References

  1. Lean MEJ, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet 2018; 391: 541
  2. Michael E J Lean, Wilma S Leslie, Alison C Barnes, Naomi Brosnahan, George Thom, Louise McCombie, et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol 2019. Published: March 6, 2019. http://dx.doi.org/10.1016/
  3. National Institutes of Health. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults — the evidence report. Obes Res1998;6:Suppl 2:51S-209S[Erratum, Obes Res 1998;6:464.
  4. Romeo S, Maglio C, Burza MA, et al. Cardiovascular events after bariatric surgery in obese subjects with type 2 diabetes. Diabetes Care2012;35:2613-2617
  5. The Look AHEAD Research Group. Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes. N Engl J Med 2013; 369:145-154 DOI: 10.1056/NEJMoa1212914
  6. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA (2008) 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359(15):1577–1589. https://doi.org/10.1056/NEJMoa0806470
  7. Koster-Rasmussen R, Simonsen MK, Siersma V, Henriksen JE, Heitmann BL, de Fine Olivarius N (2016) Intentional weight loss and longevity in overweight patients with type 2 diabetes: a population-based cohort study. PLoS One 11(1):e0146889. https://doi.org/10.1371/journal.pone.0146889
  8. Piepoli MF, Hoes AW, Agewall S et al (2016) 2016 European guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts): developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 37(29):2315–2381
  9. Jean Strelitz, Amy L. Ahern, Gráinne H. Long, et al. Moderate weight change following diabetes diagnosis and 10 year incidence of cardiovascular disease and mortality. Diabetologia https://doi.org/10.1007/s00125-019-4886-1

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