Effects of alpha-glucosidase-inhibiting drugs on acute postprandial glucose and insulin responses: a systematic review and meta-analysis

Background/objectives: Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase-inhibiting (AGI) drugs on acute PPG and PPI responses. Methods: We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental PPG and PPI levels were calculated as outcomes. Meta-analyses, stratified by diabetes state, were performed by using random effects models. Results: The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (−1.5 mmol/l mean PPG [95% CI −1.9, −1.1] by acarbose, and −1.6 [−1.9, −1.4] by miglitol) as compared to individuals without diabetes (−0.4 [95% CI −0.5, −0.3] by acarbose, and −0.6 [−0.8, −0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43−54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes. Conclusions: The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by AGI drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions

Reducing postprandial glucose in dietary intervention studies and the magnitude of the effect on diabetes-related risk factors: a systematic review and meta-analysis

Purpose: Reducing postprandial hyperglycemia has beneficial effects on diabetesrelated risk factors, but the magnitude of the reduction needed to achieve such an effect is unknown. To quantify the relationship of acute glucose and insulin postprandial responses with longer-term effects on diabetes-related risk factors by performing a systematic review and meta-analysis of dietary intervention studies. Methods: We systematically searched EMBASE and MEDLINE. Dietary intervention studies among any human population aiming to reduce postprandial glycaemia, with actual measures of postprandial glucose (PPG) and/or insulin (PPI) as acute exposures (incremental area under the curve, iAUC) as well as markers of glucose metabolism (fasting glucose, HbA1c) and insulin sensitivity (fasting insulin, HOMA-IR) after at least 4 weeks of diet intervention as outcomes, were included. Meta-analyses were performed for the effects on acute exposures and on diabetes-related risk factors. The relationship between changes in acute exposures and changes in risk factor outcomes was estimated by meta-regression analyses. Results: Out of the 13004 screened papers, 14 papers with 14 comparisons were included in the quantitative analysis. The dietary interventions acutely reduced mean PPG (mean difference (MD), -0.27 mmol/l; 95% CI, -0.41 to -0.14) but not mean PPI (MD, -7.47 pmol/l; 95% CI, -16.79 to 1.86). No significant overall effects on fasting glucose and insulin. HbA1c was reduced by -0.20% (95%CI -0.35 to -0.05). Changes in acute PPG were significantly associated with changes in fasting plasma glucose (FPG) (per 10% change in PPG: β = 0.085 (95% CI, 0.003, 0.167), k=14), but not with fasting insulin (β = 1.20 (95% CI, -0.32, 2.71), k=12). Changes in acute PPI were not associated with changes in FPG (per 10% change in PPI: β = -0.017 (95% CI, -0.056, 0.022), k=11). Conclusions: Only a limited number of postprandial glucose lowering dietary intervention studies measured acute postprandial exposures to PPG/PPI during the interventions. In this small heterogeneous set of studies, an association was found between the magnitude of the acute postprandial responses and the change in fasting glucose but no other outcomes. More studies are needed to quantify the relationship between acute postprandial changes and long-term effects on risk factors

Reducing postprandial glucose in dietary intervention studies and the magnitude of the effect on diabetes-related risk factors: a systematic review and meta-analysis

Purpose: Reducing postprandial hyperglycemia has beneficial effects on diabetes-related risk factors, but the magnitude of the reduction needed to achieve such an effect is unknown. The purpose of the study was to quantify the relationship of acute glucose and insulin postprandial responses with longer-term effects on diabetes-related risk factors by performing a systematic review and meta-analysis of dietary intervention studies. Methods: We systematically searched EMBASE and MEDLINE. Dietary intervention studies among any human population aiming to reduce postprandial glycemia, with actual measures of postprandial glucose (PPG) and/or insulin (PPI) as acute exposures (incremental area under the curve, iAUC) as well as markers of glucose metabolism (fasting glucose, HbA1c) and insulin sensitivity (fasting insulin, HOMA-IR) after at least 4 weeks of diet intervention as outcomes were included. Meta-analyses were performed for the effects on acute exposures and on diabetes-related risk factors. The relationship between changes in acute exposures and changes in risk factor outcomes was estimated by meta-regression analyses. Results: Out of the 13,004 screened papers, 13 papers with 14 comparisons were included in the quantitative analysis. The dietary interventions acutely reduced mean PPG [mean difference (MD), − 0.27 mmol/l; 95% CI − 0.41 to − 0.14], but not mean PPI (MD − 7.47 pmol/l; 95% CI − 16.79 to 1.86). There were no significant overall effects on fasting glucose and insulin. HbA1c was reduced by − 0.20% (95% CI − 0.35 to − 0.05). Changes in acute PPG were significantly associated with changes in fasting plasma glucose (FPG) [per 10% change in PPG: β = 0.085 (95% CI 0.003, 0.167), k = 14], but not with fasting insulin [β = 1.20 (95% CI − 0.32, 2.71), k = 12]. Changes in acute PPI were not associated with changes in FPG [per 10% change in PPI: β = − 0.017 (95% CI − 0.056, 0.022), k = 11]. Conclusions: Only a limited number of postprandial glucose-lowering dietary intervention studies measured acute postprandial exposures to PPG/PPI during the interventions. In this small heterogeneous set of studies, an association was found between the magnitude of the acute postprandial responses and the change in fasting glucose, but no other outcomes. More studies are needed to quantify the relationship between acute postprandial changes and long-term effects on risk factors

Reducing postprandial glucose in dietary intervention studies and the magnitude of the effect on diabetes-related risk factors: a systematic review and meta-analysis

Purpose: Reducing postprandial hyperglycemia has beneficial effects on diabetesrelated risk factors, but the magnitude of the reduction needed to achieve such an effect is unknown. To quantify the relationship of acute glucose and insulin postprandial responses with longer-term effects on diabetes-related risk factors by performing a systematic review and meta-analysis of dietary intervention studies. Methods: We systematically searched EMBASE and MEDLINE. Dietary intervention studies among any human population aiming to reduce postprandial glycaemia, with actual measures of postprandial glucose (PPG) and/or insulin (PPI) as acute exposures (incremental area under the curve, iAUC) as well as markers of glucose metabolism (fasting glucose, HbA1c) and insulin sensitivity (fasting insulin, HOMA-IR) after at least 4 weeks of diet intervention as outcomes, were included. Meta-analyses were performed for the effects on acute exposures and on diabetes-related risk factors. The relationship between changes in acute exposures and changes in risk factor outcomes was estimated by meta-regression analyses. Results: Out of the 13004 screened papers, 14 papers with 14 comparisons were included in the quantitative analysis. The dietary interventions acutely reduced mean PPG (mean difference (MD), -0.27 mmol/l; 95% CI, -0.41 to -0.14) but not mean PPI (MD, -7.47 pmol/l; 95% CI, -16.79 to 1.86). No significant overall effects on fasting glucose and insulin. HbA1c was reduced by -0.20% (95%CI -0.35 to -0.05). Changes in acute PPG were significantly associated with changes in fasting plasma glucose (FPG) (per 10% change in PPG: β = 0.085 (95% CI, 0.003, 0.167), k=14), but not with fasting insulin (β = 1.20 (95% CI, -0.32, 2.71), k=12). Changes in acute PPI were not associated with changes in FPG (per 10% change in PPI: β = -0.017 (95% CI, -0.056, 0.022), k=11). Conclusions: Only a limited number of postprandial glucose lowering dietary intervention studies measured acute postprandial exposures to PPG/PPI during the interventions. In this small heterogeneous set of studies, an association was found between the magnitude of the acute postprandial responses and the change in fasting glucose but no other outcomes. More studies are needed to quantify the relationship between acute postprandial changes and long-term effects on risk factors

Effects of Alpha-Glucosidase Inhibiting Drugs on Acute Postprandial Glucose and Insulin Responses: a Systematic Review and Meta-Analysis

Background/Objectives: Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase inhibiting (AGI) drugs on acute postprandial glucose and insulin responses. Methods: We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental postprandial glucose and insulin levels were calculated as outcomes. Metaanalyses, stratified by diabetes state, were performed by using random effects models. Results: The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (-1.5 mmol/l mean PPG [95%CI -1.9, -1.1] by acarbose, and -1.6 [-1.9, -1.4] by miglitol) as compared to individuals without diabetes (-0.4 [95%CI -0.5, - 0.3] by acarbose, and -0.6 [-0.8, -0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43-54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes. Conclusions: The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by alpha-glucosidase inhibiting drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions.</p

Phenotypic and lifestyle determinants of HbA1c in the general population-The Hoorn Study

AIM: To investigate the relative contribution of phenotypic and lifestyle factors to HbA1c, independent of fasting plasma glucose (FPG) and 2h post-load glucose (2hPG), in the general population. METHODS: The study populations included 2309 participants without known diabetes from the first wave of the Hoorn Study (1989) and 2619 from the second wave (2006). Multivariate linear regression models were used to analyze the relationship between potential determinants and HbA1c in addition to FPG and 2hPG. The multivariate model was derived in the first wave of the Hoorn Study, and replicated in the second wave. RESULTS: In both cohorts, independent of FPG and 2hPG, higher age, female sex, larger waist circumference, and smoking were associated with a higher HbA1c level. Larger hip circumference, higher BMI, higher alcohol consumption and vitamin C intake were associated with a lower HbA1c level. FPG and 2hPG together explained 41.0% (first wave) and 53.0% (second wave) of the total variance in HbA1c. The combination of phenotypic and lifestyle determinants additionally explained 5.7% (first wave) and 3.9% (second wave). CONCLUSIONS: This study suggests that, independent of glucose, phenotypic and lifestyle factors are associated with HbA1c, but the contribution is relatively small. These findings contribute to a better understanding of the low correlation between glucose levels and HbA1c in the general population

Phenotypic and lifestyle determinants of HbA1c in the general population-The Hoorn Study.

AIM:To investigate the relative contribution of phenotypic and lifestyle factors to HbA1c, independent of fasting plasma glucose (FPG) and 2h post-load glucose (2hPG), in the general population. METHODS:The study populations included 2309 participants without known diabetes from the first wave of the Hoorn Study (1989) and 2619 from the second wave (2006). Multivariate linear regression models were used to analyze the relationship between potential determinants and HbA1c in addition to FPG and 2hPG. The multivariate model was derived in the first wave of the Hoorn Study, and replicated in the second wave. RESULTS:In both cohorts, independent of FPG and 2hPG, higher age, female sex, larger waist circumference, and smoking were associated with a higher HbA1c level. Larger hip circumference, higher BMI, higher alcohol consumption and vitamin C intake were associated with a lower HbA1c level. FPG and 2hPG together explained 41.0% (first wave) and 53.0% (second wave) of the total variance in HbA1c. The combination of phenotypic and lifestyle determinants additionally explained 5.7% (first wave) and 3.9% (second wave). CONCLUSIONS:This study suggests that, independent of glucose, phenotypic and lifestyle factors are associated with HbA1c, but the contribution is relatively small. These findings contribute to a better understanding of the low correlation between glucose levels and HbA1c in the general population

Size and shape of the associations of glucose, HbA1c, insulin and HOMA-IR with incident type 2 diabetes: the Hoorn Study

AIMS/HYPOTHESIS: Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA1c, fasting insulin and HOMA-IR with incident type 2 diabetes mellitus. METHODS: The study population included 1349 participants aged 50-75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations. RESULTS: After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA1c, 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA1cwith incident diabetes were non-linear, rising more steeply at higher values. CONCLUSIONS/INTERPRETATION: FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA1c, HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers

Risicobenadering voor de Nederlandse zoetwatervoorziening : methode ontwikkeling en toepassing op drie casestudies in Nederland

In 2016 is door twee deelprojecten gezamenlijk gewerkt aan het verder ontwikkelen en toepassen van de risicobenadering voor droogte in Nederland. Het gaat enerzijds om KPP DPZW IA economie (Kennis voor het Primaire Proces, Deltaprogramma Zoetwater, Instrumentarium Afwegingen, onderdeel economie, hierna IA economie) en anderzijds om het Nederlandse droogtedeel van het Horizon2020 project IMPREX (IMproving PRedictions and management of hydrological EXtremes, hierna IMPREX). Dit rapport beschrijft de resultaten van de twee deelprojecten zoals uitgevoerd in 2016. Hoofdstuk 2 presenteert de analyse van de landelijke toepasbaarheid. Hoofdstuk 3 richt zich op de methodiek en de ontwikkelde tools. Hoofdstuk 4 beschrijft de resultaten voor onzekerheid rondom waterbeschikbaarheid in het Hoofdwatersysteem en mogelijkheden om extremen in beeld te brengen. Daarna worden de twee regionale casestudies beschreven in aparte hoofdstukken. In hoofdstuk 7 worden algemene conclusies gepresenteerd