Here, we inform the regression and progression rates of dysglycemia in a set of adults with impaired fasting glucose living in urban centers of Central Mexico. After ~ 2.5 years of follow-up, 22.6% subjects regressed to normoglycemia, 36% remained as impaired fasting glucose and 22.9% progressed to type 2 diabetes. We showed that age, lower BMI, and lower glycemia were the main clinical predictors associated with regression to normoglycemia, and that the addition of metabolomics information did not materially improved the predictive capability of a model that included clinical variables alone. Taken together, our findings may have implications for cardiovascular prevention strategies as they identify a set of clinical features that are associated with less likelihood for developing type 2 diabetes among individuals with impaired fasting glucose.
To our knowledge, this is the first report of the rate of regression in Latin-American populations, a population that is characterized by the high conversation rates from impaired fasting glucose to type 2 diabetes. There are few studies that have focused on regression to normoglycemia despite it is the most common and profitable outcome in the midterm and long-term respectively. Our results allow us to compare the regression rates in Mexicans compared against other populations. The rate found in this study is higher to what was found in an Asian and in a multiethnic cohort at 1 and 10 years of follow-up (15,27). Our findings concurs with data from the Diabetes Prevention Program (DPP) showing that within treatment groups, normoglycemia was attained once in 23% (170/736), 25% (161/647) and 23% (137/607), in intensive life style, metformin, and placebo treatment arms, respectively (17). Our findings reinforce the identification of individuals with impaired fasting glucose to advance the prevention of type 2 diabetes, to overcome the burden of cardiometabolic complications. The identification of the variables that predict a higher likelihood for having regression may be useful to prioritize access to care, particularly in populations where the medical access is limited. Our findings confirm the importance of fasting glucose and BMI in the profile of the subjects who achieve regression to normoglycemia and expand them to age, which has been shown very relevant for maintaining normal glucose levels (28) (29).
A novel contribution of our study is that we investigated the associations of circulating metabolites with regression to normoglycemia. In this study we identified 18 associated with regression to normoglycemia. Metabolites associated with regression to normoglycemia highlight features of lipid content in specific lipoprotein subfractions. We showed that the amount of phospholipids in medium or large LDL particles of free cholesterol in small LDL was associated with lower likelihood to regress to normoglycemia, while lipid components in large HDLc particles were associated with increased likelihood to regress to normoglycemia.
Although, there is lack of information regarding the clinical implications and usability of HDL particles, some evidence describes a negative relationship between the number of large HDL particles and cardiovascular disease, and conversely, a reduced mean HDL size is equally associated with cardiovascular disease in large-scale clinical studies(33). This direction of the effect was confirmed by our study in the associations with insulin sensitivity and secretion where larger HDL particles had a negative association with insulin sensitivity in subject who remained as impaired fasting glucose or regressed to normoglycemia. Our findings support evidence of the clinical usability of a detailed lipid metabolomic profiling and their clinical consequences. Although further studies are needed, HDL composition profile can be used as biomarkers of cardiovascular deterioration even in an early state such as impaired fasting glucose. However, prioritized metabolites marginally improved the predictive capability to regress to normoglycemia suggesting that metabolomic contributions in regression to normoglycemia are more related to the identification of metabolic pathways over prediction.
In our study we found that individuals with low concentrations of albumin at baseline were more likely to regress to normoglycemia, even adjusting for age, BMI and fasting glucose concentrations (p < 0.003). Serum albumin is the main protein of the plasma, its main function is the regulation of the colloidal osmotic pressure of the blood (30). Previous reports show inverse associations with type 2 diabetes-related traits (31)(32). Some differences might lie in the studied sample size, most of studies have been studied the risk of healthy individuals to develop type 2 diabetes, whereas our sample is composed by high-risk subjects with impaired fasting glucose. Therefore, the protective capability conferred by the albumin thought its role as antioxidant might be diminished.
There are several limitations in our study including the use of only one measurement of fasting glucose measurement to define regression to normoglycemia. This limits to identify the inter-individual variability of fasting glucose measurements but has the advantage to reduce costs and possible withdrawals that of future visits imply. Our finding need to be confirmed in an independent cohort and other populations at high risk of type 2 diabetes, with longer follow-up times. We acknowledge that this sample is composed only for Latino subjects, further studies in other high-risk populations are need it. Finally, additional studies to test the treatment response will complement the evidence in regards the usability of these variables.