Abstract
We investigated biological determinants that would associate with the response to a diet and weight loss programme in impaired glucose regulation (IGR) people using sequential window acquisition of all theoretical fragment ion spectra (SWATH) mass spectrometry (MS), a data acquisition method which complement traditional mass spectrometry-based proteomics techniques. Ten women and 10 men with IGR underwent anthropometric measurements and fasting blood tests. SWATH MS was carried out with subsequent immunoassay of specific peptide levels. After a six-month intervention, 40% of participants lost 3% or more in weight, 45% of patients remained within 3% of their starting weight and 15% increased their weight by 3% or more. Hemoglobin A1c (HbA1C) level was reduced with weight loss with improvements in insulin sensitivity. SWATH MS on pre-intervention samples and subsequent principal component analysis identified a cluster of proteins associated with future weight loss, including insulin-like growth factor-II (IGF-II) and Vitamin D binding protein. Individuals who lost 3% in weight had significantly higher baseline IGF-II levels than those who did not lose weight. SWATH MS successfully discriminated between individuals who were more likely to lose weight and potentially improve their sensitivity to insulin. A higher IGF-II baseline was predictive of success with weight reduction, suggesting that biological determinants are important in response to weight loss and exercise regimes. This may permit better targeting of interventions to prevent diabetes in the future.
Highlights
There remains uncertainty as to what are the determinants of progression from impaired glucose regulation (IGR) or pre-diabetes to type 2 diabetes (T2MD) in relation to what may assist in the prediction of response to lifestyle interventions.There is strong evidence to suggest that without any lifestyle or medical intervention, in particular weight loss and physical activity, more than 50% of people with IGR will develop T2DM accompanied by an increased risk of cardiovascular disease and cardiovascular death over a period of 10 years [1]
The descriptive analysis shows the mean age of the participants before the intervention (61.5 ± 4.83, male; 60.2 ± 2.73, female), initial weight (108.2 ± 9.18, male; 94.8 ± 5.16, female), height (175.8 ± 2.85, male; 161.9 ± 2.46, female), hip-waist ratio (1.00 ± 0.02, male; 0.90 ± 0.01, female) and body mass index (BMI) (35.0 ± 2.88, male; 36.2 ± 1.94, female)
We show that a higher insulin-like growth factor-II (IGF-II) is predictive of weight loss
Summary
There remains uncertainty as to what are the determinants of progression from impaired glucose regulation (IGR) or pre-diabetes to type 2 diabetes (T2MD) in relation to what may assist in the prediction of response to lifestyle interventions.There is strong evidence to suggest that without any lifestyle or medical intervention, in particular weight loss and physical activity, more than 50% of people with IGR will develop T2DM accompanied by an increased risk of cardiovascular disease and cardiovascular death over a period of 10 years [1]. In many areas of the UK, people with impaired glucose regulation (IGR) are being identified and they are being offered a lifestyle change through the National Diabetes Prevention Programme (NDPP) [2]. Uk/resources/igt-care-call/) [3], a telephone based modular intervention programme, which has been proven to benefit people with impaired glucose regulation. The disruption of their physiological functions is usually associated with several disease phenotypes. In this sense, the study of these proteins and their functions has been extremely important in order to decipher the cellular mechanisms and organization of particular phenotypes [7,8]
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