Nutritional Epidemiology

During the Prevention of type 2 diabetes session at the Nordic Nutrition Conference 2020 (14-16 December), it was made clear that prevention of type 2 diabetes is highly achievable, as has been proven in some important studies over the past decades. Below follows a summary of a few of those studies. 

Finnish DPS study

The Finnish Diabetes Prevention Study (DPS) was among the first diabetes prevention trials ever made (1). In the study, 523 individuals with impaired glucose tolerance were recruited between 1993-1998. Individuals were randomized to a lifestyle intervention group or a control group. Study participants had seven sessions with a nutritionist during the first year, and four per year for the remaining of the study. The lifestyle intervention was constituted by the following goals and advice: 

1. Weight reduction: 5% or more
2. Fat intake <30E%
3. Saturated fat intake <10E% 
4. Fiber ≥ 15 g per 1000 kcal
5. Exercise: moderate ≥ 30 min/day 

The incidence of diabetes was 58% lower in the intervention group than in the control group after an average 3.2 years (1). These results are in line with those of the three other diabetes prevention trials from the same era: 

1. US Diabetes Prevention Program (n=3234 recruited 1991-1996) could see that incidence was reduced by 58% with the lifestyle intervention and 31% with the metformin intervention compared to the control group after an average of 2.8 years (2). 
2. Da Qing Diabetes Study (n=577 recruited 1986) could see decreased incidence in type 2 diabetes in the diet group, physical activity group and the diet+physical activity group (36-53%) compared to control after 6 years (3). 
3. Indian Diabetes Prevention Programme, (n=531 recruited 2001-2002) showed that lifestyle management and metformin treatment reduced the type 2 diabetes equally (ca 28%) compared to control after 3 years (4). 

From these studies, it became evident that type 2 diabetes can be prevented with lifestyle modifications. 

DIRECT study

The DIRECT (Diabetes Remission Clinical Trail) study had their focus on reversing newly diagnosed diabetic patients rather than on diabetes prevention. Their objective was based on that other studies have indicated that a 15 kg weight loss could normalise life expectancy in individuals with type 2 diabetes. 

In the DIRECT study, 298 patients who have been diagnosed with type 2 diabetes maximum 6 years ago were taken out of their medications and instead started a 3 months low calorie diet with total diet replacement. After three months, participants were gradually reintroduced to solid foods for two months and after that followed 24 months of weight maintenance. All of this was performed within the primary health care setting. 

After 1 year, 46% in the intervention group had achieved remission (5), and at 2 years, 36% were in remission (6). In line with this were a wide range of other health markers improved in the intervention group, and the magnitude of improvements was related to the amount of weight lost and maintained.

This study indicates how plausible type 2 diabetes remission actually is within the primary health care, as long as we have enough resources to focus on this issue. Most excitingly is that this is currently being implemented within the primary health care in the UK. 

PREVIEW study

The PREVIEW (PREventing Diabetes through Interventions in Europe and the World) is a multi-center randomized controlled trial where individuals with prediabetes were included (7). The interventions started with a two months weight loss phase using a low-calorie diet (as in DIRECT). After that, the goal was to compare to different dietary regimens for weight loss maintenance for 34 months; one considered a standard diabetes preventing diet and another with higher protein content and lower glycaemic index (GI) based on the successful results from the DiOGenes study (8). So, a high protein-low GI diet was compared to a moderate protein-medium GI diet and both of these diets were paired with either a high or moderate intensive physical activity scheme, resulting in four different intervention arms. 

The study started in 2013 and was finished in 2018, and the main results were recently published (7). A total of 2326 individuals were recruited to the study, but to continue to the weight maintenance phase, a minimum of 8% weight loss was necessary. This was achieved by 80% of the participants (n=1857). Among these, 3,1% developed type 2 diabetes during the three year long study. This was much lower than expected, indicating that the interventions were effective in reducing the type 2 diabetes incidence. Further, there was no difference in incidence between the different intervention groups. Weight loss and various measures of glucose homeostasis were also the same in all groups, with the exception for normoglycemia that was significantly less achieved in the high protein-low GI diet with high intensity training. But why this is, is difficult to explain. 

So overall, both dietary regimes were effective in reducing type 2 diabetes risk, and the incidence were much lower than expected. However, of major concern are indications of a limited adherence to the interventions, especially to the high protein intake, and a rather high drop-out rate, 26% year 1 and 41 % year 3, equally distributed between intervention groups. 

Conclusion

All three presentations during this session of the Nordic Nutrition Conference 2020 indicated how the ability to prevent or revert type 2 diabetes using diet and lifestyle interventions is constantly higher than we expect. The successful actions for tackling type 2 diabetes, in for example primary health care, have now been shown time after time. So, one can certainly wonder why more is not implemented? Why isn’t more done when we know of many alternative ways in how to prevent type 2 diabetes? And luckily, the research indicates that it is not the details that are important (for example whether protein intake is 15 or 25E%), it’s about getting enough encouraging visits and phone calls to keep the intervention going. We don’t need difficult expert dietary advice, we need simple weight loss advice for healthy living, but we need them often and with engagement from the health care. 

1. Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. The New England journal of medicine 2001;344(18):1343-50. doi: 10.1056/nejm200105033441801.
2. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. The New England journal of medicine 2002;346(6):393-403. doi: 10.1056/NEJMoa012512.
3. Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes care 1997;20(4):537-44. doi: 10.2337/diacare.20.4.537.
4. Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V, Indian Diabetes Prevention P. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia 2006;49(2):289-97. doi: 10.1007/s00125-005-0097-z.
5. Lean MEJ, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The Lancet 2018;391(10120):541-51. doi: 10.1016/s0140-6736(17)33102-1.
6. Lean MEJ, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, 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. The Lancet Diabetes & Endocrinology 2019;7(5):344-55. doi: 10.1016/s2213-8587(19)30068-3.
7. Raben A, Vestentoft PS, Brand-Miller J, Jalo E, Drummen M, Simpson L, Martinez JA, Handjieva-Darlenska T, Stratton G, Huttunen-Lenz M, et al. The PREVIEW intervention study: Results from a 3-year randomized 2 x 2 factorial multinational trial investigating the role of protein, glycaemic index and physical activity for prevention of type 2 diabetes. Diabetes Obes Metab 2020. doi: 10.1111/dom.14219.
8. Larsen TM, Dalskov SM, van Baak M, Jebb SA, Papadaki A, Pfeiffer AF, Martinez JA, Handjieva-Darlenska T, Kunešová M, Pihlsgård M, et al. Diets with high or low protein content and glycemic index for weight-loss maintenance. The New England journal of medicine 2010;363(22):2102-13. doi: 10.1056/NEJMoa1007137.