Effective prevention of cardio-metabolic diseases starts as early as possible, preferably by lifestyle adjustments, and should be intensified according to increasing risk status of the patient. Understanding the individual patient’s risk status is fundamental in this progression. On the other hand, lifestyle measures should be compatible with daily routines and social life of the patient in order to achieve long-term adherence, and they should be feasible for health care providers. One strategy to achieve this is to limit the more time- and labour-intensive interventions to patients at higher risk.
Fritsche et al. test this concept in a systematic manner in their recent study . They investigate two risk phenotypes of pre-diabetes: a high risk and a low risk phenotype, defined based on insulin secretion, insulin sensitivity and liver fat content (Figure). The high risk group had been shown before to include patients with beta cell dysfunction and/or insulin resistant non-alcoholic fatty liver disease (NAFLD)  and to respond to conventional lifestyle interventions less frequently . It was therefore argued that these patients might specifically benefit from an intensified intervention. Within the one-year study duration, patients of the “conventional” group received eight counselling sessions in total and were advised to exercise three hours per week. Patients of the “intensified” group received 16 coaching sessions withing the one year with advice to exercise 6 hours weekly. Feedback on physical activity was given based on patients’ accelerometer data, personal diet and exercise protocols and weight loss achieved. Patients of the control group received only one initial session on lifestyle measures.
Within the high risk group, intensive lifestyle intervention led to greater changes in glucose levels at two hours post-challenge glucose values in the OGGT - the primary study endpoint - than conventional lifestyle intervention group . Within the low risk group, there was no difference in the primary endpoint between patients receiving conventional lifestyle intervention and the control group. However, low risk participants receiving conventional lifestyle did achieve normal glucose tolerance during the three years of follow-up more frequently than patients of the control group.
Also regarding secondary outcome parameters (BMI, insulin sensitivity, liver fat content, Framingham 10-year-cardiovascular-risk), patients within the high risk group benefitted more from intensified therapy than from conventional therapy, with the exception of insulin secretion. Interestingly, these changes in liver fat content and insulin sensitivity were independent of change in body weight in the high-risk participants. In low-risk subjects, only BMI and fasting glucose improved with conventional lifestyle intervention as compared to controls, with no differences for the other secondary endpoints.
Overall, improvement in postprandial glucose metabolism was associated with meeting an aggregated index of lifestyle goals (diet, exercise, weight). Among patients receiving conventional therapy, a higher percentage of low risk participants met aggregated lifestyle behavioural goals than among high risk participants. Meeting aggregated lifestyle goals was similar between intensified and conventional therapy among high risk patients, with more individuals reaching exercise goals in the conventional group, and more individuals reaching weight goals in the intensified intervention group. Of note amount of recommended exercise was six hours per week in the intensified versus three hours per week in the conventional lifestyle intervention group.
While the study focussed on glucose metabolism, with cardiovascular risk only as a secondary outcome, the overall concept of intensified treatment for patients in higher risk categories - specifically represented by more frequent counselling intervals and combined with feedback on patients behaviour - are important concepts for transferring lifestyle interventions from study settings into clinical routine. Those “presence” feedback sessions may be combined with face-to-face telemonitoring sessions to save travelling time while still allowing for personal feedback. It appears especially important not to stop counselling sessions, as we have learned from Look AHEAD that weight loss achievements get lost after the stop of frequent counselling sessions .
Moreover, changes of liver fat content and insulin sensitivity were independent of change in body weight in the high-risk population, underlining the pleiotropic effects of exercise, especially glucose uptake by the trained skeletal muscle. In contrast, earlier and more recent meta-analyses had observed associations between loss of liver fat and body weight loss [5, 6]. Hence, better characterization specifically of phenotypes at higher cardio-metabolic risk and their individual response to lifestyle interventions is warranted.
Figure: a high risk and a low risk phenotype, defined based on insulin secretion, insulin sensitivity and liver fat content