The Heterogeneity of Reversion to Normoglycemia According to Prediabetes Type is not Explained by Lifestyle Factors.

Background: Healthy lifestyle interventions and drug therapies are proven to have a positive preventative influence on normal glucose regulation in prediabetes. However, little is known on the specific role that these factors play on reversion to normal glycemia according to type of prediabetesMethods: We used data from the Observational prospective cohort study. The Cohort study in Primary Health Care on the Evolution of Patients with Prediabetes from 2012-2015. A total of 1184 individuals aged 30 to 74 years old were included and classified based on the ADA in three mutually exclusive groups using either fasting plasma glucose (FPG) levels (from 100-125 mg/dl, FPG group), HbA1c (5.7%–6.4%, HbA1c group) or both impaired parameters group. Information on lifestyle factors and biochemical parameters were collected at baseline Reversion to normal glucose regulation was calculated at third year of follow-up. Relationship of lifestyle factor and type of prediabetes with reversion were estimated using odds ratios (ORs) with 95% confidence intervals (95% CIs) adjusting by different groups of confounders.Results: Proportion of reversion rates were 31% for FPG group, 31% for HbA1c group and 7.9% for both altered parameters group, respectively. Optimal life style factors such as BMI<25 kg/m2[OR (95% CI): 1.90 (1.20-3.01)], high adherence to Mediterranean diet 1.78 (1.21-2.63) and absence of abdominal obesity 1.70 (1.19-2.43) were the strongest predictors for reversion to normal glucose. However, those did not modify the ORs of reversion to normal glucose. Taking as reference those with both impaired parameters, subjects with FPG impairment (FP group) had an OR of 4.87 (3.10-7.65) and 3.72 (2.39-5.78) for HbA1c group. These estimates remained almost the same after further adjustment for biochemical parameters and lifestyle factors (4.55(2.84-7.28) and 3.09 (1.92- 4.97), respectively).Conclusions: Optimal lifestyle factors showed to be a positive predictor for reversion to normal glucose regulation however, the differences of reversion risk according type of prediabetes are not explained by lifestyle factors.

Lifestyle factors and reversion to normoglycaemia by prediabetes type in PREDAPS study.

Background: Healthy lifestyle interventions and drug therapies are proven to have a positive preventative influence on normal glucose regulation in prediabetes; however, there is little evidence to support the role of these factors according to the various stage of the prediabetes stateAims: This study aims to investigate the role of lifestyle factors on the reversion to normal glucose regulation according to the different stage of the prediabetes state based on most up-to-date American Diabetes Association (ADA) guidelines.Design and Setting: Observational prospective cohort study. The Cohort study in Primary Health Care on the Evolution of Patients with Prediabetes from 2012-2015Methods: A total of 1184 individuals aged 30 to 74 years old were included and classified based on the ADA in three mutually exclusive groups using either fasting plasma glucose (FPG) levels (from 100-125 mg/dl, FPG group), HbA1c (5.7%–6.4%, HbA1c group) or both impaired parameters group. Information on lifestyle factors and biochemical parameters were collected at baseline Reversion to normal glucose regulation was calculated at third year of follow-up. Relationship of lifestyle factor and type of prediabetes with reversion were estimated using odds ratios (ORs) with 95% confidence intervals (CIs) adjusting by different groups of confounders.Results: Proportion of reversion rates were 31% for FPG group, 31% for HbA1c group and 7.9% for both altered parameters group, respectively. Optimal life style factors such as BMI<25 kg/m2[OR (95% CI): 1.90 (1.20-3.01)], high adherence to Mediterranean diet 1.78 (1.21-2.63) and absence of abdominal obesity 1.70 (1.19-2.43) were the strongest predictors for reversion to normal glucose. ORs of reversion to normal glucose were 4.87 (3.10-7.65) for FPG group and 3.72 (2.39-5.78) for HbA1c group, taking as reference those with both impaired parameters. These estimates remained almost the same after further adjustment for biochemical parameters and lifestyle factors.Conclusions: Although optimal lifestyle factors showed to be a positive predictor for reversion to normal glucose regulation, they do not seem to explain the differences according to the type of prediabetes.

MON-586 Gut Hormones Response to 24-H High Carbohydrate Overfeeding Is a Determinant of Metabolic Adaptation to Carbohydrate Intake in Healthy Individuals

Background: We previously demonstrated that short-term (24h) changes in carbohydrate (CARBOX) or fat oxidation rates in response to overfeeding diets with different macronutrient content are highly correlated within an individual, suggesting the existence of human metabolic phenotypes (carbohydrate vs. fat oxidizers). Gut hormones have a role in feeding and substrate oxidation, thus we investigated if the changes in gut hormones concentration during overfeeding diets or fasting explain the degree of metabolic flexibility in healthy humans.Methods: While residing in our clinical research unit, 67 healthy, weight-stable volunteers (37±10y, BMI: 26±4 kg/m2, body fat: 28±10%; mean±SD, 54 men) with normal glucose regulation had 24-h EE measurements in a whole-room indirect calorimeter during energy balance (EB, diet: 50% carbohydrate, 20% protein), three overfeeding diets, and fasting in a crossover design. The overfeeding diets (200% of weight-maintaining energy requirements) included diets with 20%-protein [50%-carbohydrate (SOF), 75%-carbohydrate (CNP), and 60%-fat (FNP)]. Metabolic flexibility was determined by the difference between respiratory quotient (RQ) during overfeeding/fasting from EB conditions. Plasma GLP-1, PYY, PP, and total ghrelin concentrations were measured by ELISA after an overnight fast the morning of and after each diet. Results: PYY increased after all overfeeding diets (3.4±13.1, 7.0±16.2, and 7.6±14.4 pg/mL; all p&lt;0.05, SOF, CNP and FNP respectively) and decreased with fasting (-11.6±14.2 pg/mL; p&lt;0.001). GLP-1 increased after fasting (2.7±5.8 pg/mL; p&lt;0.001) and FNP (1.3±4.5 pg/mL; p=0.02) and decreased with CNP (-0.9±6.3 pg/mL; p=0.04). PP only increased after fasting (92.8±133.4 pg/mL; p&lt;0.001), while ghrelin decreased with SOF (-31.3±108 pg/mL; p=0.02) and CNP (-43.1±120 pg/dL; p=0.005) but not with FNP (p=0.51). After adjustment for body composition and other known EE determinants, no hormonal changes were associated with the change in 24-h EE in any diet (all p&gt;0.05); however, during CNP greater decreases in GLP1, PYY, and Ghrelin were associated with less increase in 24-h RQ (all r&gt;0.25; all p&lt;0.05) while greater decrease in PP was associated with larger increase in 24-h RQ (r=-0.31, p=0.01). Specifically, greater increase in CARBOX during CNP was positively associated with the changes in GLP-1 (r=0.30; p=0.02) and Ghrelin (r=0.32, p=0.01). In a linear model, only the change in GLP-1, PP, and Ghrelin concentrations during CNP were independent predictors of the change in RQ [β=0.003; -0.0001; and 0.000006 per 1 pg/mL increase each, p=0.008; 0.02 and 0.02 respectively], after accounting for age and sex. Conclusion: In a carbohydrate rich environment, individuals with normal glucose regulation who maintain GLP-1 and ghrelin levels are better adapted to metabolize this type of diet.

Regression from prediabetes to normal glucose regulation: State of the science

Prediabetes, an intermediate stage between normal glucose regulation and type 2 diabetes, is diagnosed based on documentation of impaired fasting glucose, impaired glucose tolerance, or a hemoglobin A1c level of 5.7–6.4%. Individuals with prediabetes have increased risks for the development of type 2 diabetes and multiple vascular complications. Randomized controlled trials have demonstrated the feasibility of preventing progression from prediabetes to type 2 diabetes, using lifestyle or pharmacological interventions. Lifestyle modification has a sustained effect on diabetes prevention, whereas medications lose efficacy when discontinued. Few studies have pre-specified reversal of prediabetes as the primary outcome. There is emerging evidence that reversal of prediabetes (i.e. restoration of normal glucose regulation) confers significant protection from future diabetes and complications, including premature death, during long-term follow-up. Current lifestyle intervention protocols have been more effective in preventing progression from prediabetes to type 2 diabetes than restoring normal glucose regulation; thus, interventions that prevent type 2 diabetes in people with prediabetes do not always reverse prediabetes. Given the compelling benefits of restoration of normal glucose regulation, specific protocols for reversal of prediabetes need to be developed and tested. The design of such protocols requires a deeper understanding of the pathobiology of prediabetes and early glucose dysregulation. The present review focuses on those studies that have assessed the impact of interventions on regression of the prediabetes state and restoration of normal glucose regulation. Furthermore, we discuss alterations in adiposity, glucoregulatory mechanisms, metabolomics, inflammatory markers, and other factors that predict the initial escape from normoglycemia. Such knowledge could inform the future development of novel, refined, and targeted interventions for the reversal prediabetes/early dysglycemia and restoration of normal glucose regulation. Impact statement Prediabetes increases the risks of future type 2 diabetes (T2D) and vascular complications, risks that can be prevented by restoring normal glucose regulation (NGR). Few studies have pre-specified reversal of prediabetes and restoration of NGR as primary outcome, and current approaches that prevent T2D in people with prediabetes do not always reverse the prediabetes. The present review focuses on studies that have assessed reversal of the prediabetes, and discusses known and emerging predictors of prediabetes. We argue that fuller knowledge of such predictors could inform the discovery of novel, targeted interventions for reversing prediabetes.

Lifestyle factors and reversion to normoglycaemia by prediabetes type in PREDAPS study.

Background: Healthy lifestyle interventions and drug therapies are proven to have a positive preventative influence on normal glucose regulation in prediabetes; however, there is little evidence to support the role of these factors according to the various stage of the prediabetes state. Aims : This study aims to investigate the role of lifestyle factors on the reversion to normal glucose regulation according to the different stage of the prediabetes state based on most up-to-date American Diabetes Association (ADA) guidelines. Design and Setting: Observational prospective cohort study. The Cohort study in Primary Health Care on the Evolution of Patients with Prediabetes from 2012-2015 Methods: A total of 1184 individuals aged 30 to 74 years old were included and classified based on the ADA in three mutually exclusive groups using either fasting plasma glucose (FPG) levels (from 100-125 mg/dl, FPG group), (HbA 1c (5.7%–6.4%, HbA1c group) or both impaired parameters group. Information on lifestyle factors and biochemical parameters were collected at baseline Reversion to normal glucose regulation was calculated at third year of follow-up. Relationship of lifestyle factor and type of prediabetes with reversion were estimated using odds ratios (ORs) with 95% confidence intervals (CIs) adjusting by different groups of confounders. Results: Proportion of reversion rates were 31% for FPG group, 31% for HbA1c group and 7.9% for both altered parameters group, respectively. Optimal life style factors such as BMI<25 kg/m 2 [OR (95% CI): 1.90 (1.20-3.01)], high adherence to Mediterranean diet 1.78 (1.21-2.63) and absence of abdominal obesity 1.70 (1.19-2.43) were the strongest predictors for reversion to normal glucose. ORs of reversion to normal glucose were 4.87 (3.10-7.65) for FPG group and 3.72 (2.39-5.78) for HbA1c group, taking as reference those with both impaired parameters. These estimates remained almost the same after further adjustment for biochemical parameters and lifestyle factors. Conclusions: Although optimal lifestyle factors showed to be a positive predictor for reversion to normal glucose regulation, they do not seem to explain the differences according to the type of prediabetes.

How Family Physicians Practice the Principle of Remission Along the Glycemic Continuum

Introduction Recent evidence reveals that diabetes and prediabetes (preDM) can be reversed to normal glucose regulation (NGR) through significant weight loss, but how physicians clinically identify the principles of partial and complete remission of diabetes is largely unknown. Methods As part of the cross-sectional omnibus survey conducted in March 2019 at a professional annual meeting in the United States, physician participants answered case scenario questions about the diagnosis and documentation of patients with preDM and type 2 diabetes (T2DM). Results Of the registered conference attendees, 387 (72.7%) responded. When presented with the initial case of preDM, 201 physicians (70.8%) selected R73.03 Prediabetes. In a follow-up encounter with improved lab results, 118 physicians (58.7%) indicated that they would not chart any diabetes-related code and 62 (30.8%) would chart preDM again. When presented with the case of T2DM, 256 physicians (90.1%) indicated E11.0–E11.9 Type 2 Diabetes. In the follow-up encounter, only 38 (14.8%) coded a diagnosis reflecting remission from T2DM to prediabetes and 211 (82.4%) charted T2DM. Conclusion Physicians may be reluctant to document diabetes regression as there is little evidence for long-term outcomes and “downgrading” the diagnosis in the medical record may cause screenings to be missed. Documenting this regression in the medical record should communicate the accurate point on the continuum of glucose intolerance with both the patient and the care team.

Lifestyle factors and reversion to normoglycaemia by prediabetes type in PREDAPS study.

Background There is little evidence on how healthy lifestyle factors can explain the variation in the proportion of patients reverting to normal glucose regulation according to type of prediabetesAims To study the role of lifestyle factors on the reversion to normal glucose regulation according to type of prediabetes.Design and Setting Observational prospective cohort study. The Cohort study in Primary Health Care on the Evolution of Patients with Prediabetes from2012-2015Methods Participants were classified, according to the definition established by ADA using either fasting plasma glucose (FPG) levels between 100-125 mg/dL or HbA1c between 39-47 mmol/mol (5.7%–6.4%), in three groups. Reversion to normal glucose regulation was calculated at third year of follow-up. Relationship of lifestyle factor and type of prediabetes with reversion was estimated by means of Odds Ratios (OR) using three sequential models.Results Proportion of reversion rates were 31% for FPG group, 31% for HbA1c group and 7.9% for both altered parameters group, respectively. BMI<25 kg/m2[OR (95% CI): 1.90 (1.20-3.01)], high adherence to Mediterranean diet 1.78 (1.21-2.63) and absence of abdominal obesity 1.70 (1.19-2.43) were the strongest lifestyle predictors for reversion. Compared with those with both altered parameters, OR of reversion of prediabetes was 4.87 (3.10-7.65) for FPG group and 3.72 (2.39-5.78) for HbA1c group. These estimates remained almost the same after further adjustment for biochemical parameters and lifestyle factors.Conclusions Although optimal lifestyle factors showed to be a positive predictor, those do not seem to explain the differences according to the type of prediabetes.