Phenotypic Responses to a Lifestyle Intervention Do Not Account for Inter-Individual Variability in Glucose Tolerance for Individuals at High Risk of Type 2 Diabetes
Gráinne O’DonoghueAileen KennedyGregers S. AndersenBernadette CarrStephen ClearyEóin DurkanHeidi DavisKristine FærchPaula FitzpatrickHelena KennyNoel McCaffreyJavier MonederoEnda MurphyJohn NooneTommi SuvitaivalTanja ThyboMichael J. WheelerDorte VistisenJohn J. NolanDonal J. O’Gorman
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Background: Lifestyle interventions have been shown to delay or prevent the onset of type 2 diabetes among high risk adults. A better understanding of the variability in physiological responses would support the matching of individuals with the best type of intervention in future prevention programmes, in order to optimize risk reduction. The purpose of this study was to determine if phenotypic characteristics at baseline or following a 12 weeks lifestyle intervention could explain the inter-individual variability in change in glucose tolerance in individuals with high risk for type 2 diabetes. Methods: In total, 285 subjects with normal glucose tolerance (NGT, FINDRISC score > 12), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were recruited for a 12 weeks lifestyle intervention. Glucose tolerance, insulin sensitivity, anthropometric characteristics and aerobic fitness were measured. Variability of responses was examined by grouping participants by baseline glycemic status, by cluster analysis based on the change in glucose tolerance and by Principal Component Analysis (PCA). Results: In agreement with other studies, the mean response to the 12 weeks intervention was positive for the majority of parameters. Overall, 89% improved BMI, 80% waist circumference, and 81% body fat while only 64% improved fasting plasma glucose and 60% 2 h glucose. The impact of the intervention by glycaemic group did not show any phenotypic differences in response between NGT, IFG, and IGT. A hierarchical cluster analysis of change in glucose tolerance identified four sub-groups of "responders" (high and moderate) and "non-responders" (no response or deteriorated) but there were few differences in baseline clincal and physiological parameters or in response to the intervention to explain the overall variance. A further PCA analysis of 19 clinical and physiological univariables could explain less than half (48%) of total variability. Conclusion: We found that phenotypic characteristics from standard clinical and physiological parameters were not sufficient to account for the inter-individual variability in glucose tolerance following a 12 weeks lifestyle intervention in inidivuals at high risk for type 2 diabetes. Further work is required to identify biomarkers that complement phenotypic traits and better predict the response to glucose tolerance.Keywords:
Impaired fasting glucose
Background: The racial variation in genetic susceptibility of Type2 diabetes mellitus is well established. The stages of impaired fasting glucose (IFG) and/or Impaired glucose tolerance (IGT) (collectively known as ‘prediabetic stages) are combined to be intermediate in the natural history of diabetes, but their genetic susceptibility are still a matter of investigation. Family study is the primary step to explore genetic susceptibility. In particular, there has been no study in Bangladesh related to genetics of prediabetes. Objectives: The present study aimed to explore the genetic susceptibility of prediabetes in Bangladeshi population by observing the clustering of dysglycemia in first degree relatives of prediabetes. Methodology: The study was designed as an experimental group comparison study. Newly detected prediabetic subjects (isolated IFG, IGT, IFG+IGT) were collected from BIRDEM OPD and reconfirmed by OGTT following WHO guidelines and sub grouped. Relatives of the prediabetes, up to first generation, were included as cases and termed as R-IFG (first degree relatives of IFG), R-IGT (first degree relatives of IGT), R-IFG-IGT (first degree relatives of IFG-IGT) corresponding to the subgroups of prediabetes. Each relative underwent an OGTT following the same guideline. Blood glucose was measured by glucose oxidase method. Results: Different types of prediabetic subjects (IFG, IGT, IFG+IGT) and their first degree relatives (R_IFG, R_IGT, R_IFG+IGT) were studied. Among 41 first degree relatives of IFG (R_IFG), 2 (4.9%) had IFG, 4 (9.8%) had IGT, 1 (2.4%) had combined IFG+IGT, 5 (12.5%) had T2 DM and 29 (70.7%) had normoglycemia. Among 116 first degree relatives of IGT (R_IGT) none (0.00%) had IFG, 15 (12.9%) had IGT, 2 (1.7%) had combined IFG+IGT, 22 (19%) had diabetes and 77 (66.4%) having absolutely normal OGTT reports. Among 76 first degree relatives of IFG+IGT (R_IFG+IGT), 2 (2.6%) had IFG, 4 (5.3%) had IGT, 1 (1.3%) had combined IFG+IGT, 19 (25%) had diabetes and 50 (65.8%) were normoglycemic. Conclusion: Clustering of pre-diabetes and diabetes is present in families of prediabetic subjects and they should be taken as a major target for primary prevention of these disorders. Key words: Prediabetes; IFG; IGT; IFG+IGT; First degree relatives; Glucose intolerance. DOI: 10.3329/jbsp.v29i1.7167J Bangladesh Coll Phys Surg 2011; 29:21-26
Impaired fasting glucose
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It is well established that individuals who have prediabetes either impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) have high risk to develop diabetes. However, it is unclear whether the rate of progression to diabetes is different between these two categories. Lifestyle modification has been recommended for diabetes prevention in these high-risk groups. However, given the differences in their pathophysiology, it is possible that these subtypes of prediabetes condition may have different responses to lifestyle modification. The present review was to summarize the risk of progression to diabetes and the effectiveness of lifestyle intervention for diabetes prevention in individuals who have isolated IGT or isolated IFG or combined. The risk of progression to diabetes is highest in combined IFG and IGT subtype. Individuals who have isolated IFG by the American Diabetes Association criteria (100 to 125 mg/dl) has lower risk of progression to diabetes than those with World Health Organization criteria (110 to 125 mg/dl) and the latter has similar or higher risk of incident diabetes than those with isolated IGT. Lifestyle modification is most effective in individuals with IGT (with or without IFG) but is less effective in those with isolated IFG. In conclusion, The risk of progression to diabetes and the effectiveness of lifestyle intervention for diabetes prevention are disparate between prediabetes subtypes. Given the paucity of diabetes prevention data in individuals with isolated IFG, more studies dedicated to this subtype is required. Keywords: Impaired fasting glucose, Impaired glucose tolerance, Prediabetes, Type 2 diabetes, Lifestyle intervention, Diabetes prevention DOI: doi.org/10.35755/jmedassocthai.2020.08.11222 Received 26 Feb 2020 | Revised 7 May 2020 | Accepted 8 May 2020
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Background The American Diabetes Association (ADA) 2003 diagnostic criteria divide impaired glucose tolerance (IGT) into isolated impaired glucose tolerance with normal fasting glucose (I-IGT, IGT+NFG) and impaired glucose tolerance combined with impaired fasting glucose (IGT+IFG), while the World Health Organization (WHO) 1999 criteria do not. The aim of this meta-analysis was to evaluate whether IGT should be divided into I-IGT (IGT+NFG) or IGT+IFG according to their risk of progression to type 2 diabetes. Methods The MEDLINE and EMBASE were searched to identify prospective cohort studies published in English prior to April 18, 2020. Review Manager 5.3 was used to calculate the pooled risk ratios (RRs) and 95% confidence intervals (CIs) as summary statistics for each included study. Results Sixteen eligible studies ( n = 147,006) were included in the analysis. The subsequent incidence of type 2 diabetes was lower in the I-IGT (IGT+NFG) group than in the IGT+IFG group (0.45 [95% CI 0.37, 0.55] according to WHO 1999 criteria and 0.59 [95% CI 0.54, 0.66] according to ADA 2003 criteria). It was higher in the I-IFG, I-IGT (IGT+NFG), and IGT+IFG groups than in the normoglycemic group (95% CI of 5.53 [3.78, 8.08], 5.21 [3.70, 7.34], and 11.87 [7.33, 19.20] according to the WHO 1999 criteria and 95% CI of 2.66 [2.00, 3.54], 3.34 [2.81, 3.97], and 6.10 [4.72, 7.88] according to the ADA 2003 criteria). In general, the incidence of diabetes in the IGT+IFG group was the highest in the prediabetic population. Conclusions The present meta-analysis suggested that the established WHO diagnostic criteria for IGT should be revised to separately identify individuals with IGT+NFG or IGT+IFG.
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To evaluate the risk of diabetes in subjects with impaired fasting glycemia (IFG) as compared with impaired glucose tolerance (IGT) and normal glucose tolerance.Men (1223) and women (1370) aged 45-64 years and free of diabetes at baseline were followed-up for 10 years, with 26 737 person years accumulated. The incident diabetic cases were identified through the national Drug Register and the Hospital Discharge Register.During the 10 years of follow-up, 53 (4.3%) men and 47 (3.4%) women developed diabetes. IFG alone defined 22 (15.5/1000 person years) diabetic cases, which was higher than for subjects with normal fasting glucose. Subjects with isolated IGT identified an additional 34 cases (155% more) which could not be defined by IFG alone. The area under the ROC curve was larger for 2-h glucose (0.77, 95% CI 0.72-0.82) than for fasting glucose (0.65, 0.58-0.71). The multivariate adjusted Cox hazard ratio was higher for isolated IGT (3.9, 95% CI 2.4-6.2) than for isolated IFG (2.3, 0.9-5.7) as compared with subjects with neither IFG nor IGT.Both IFG and IGT are risk predictors for diabetes, but IGT defines a much larger target population for prevention.
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The concept of impaired fasting glucose(IFG) was firstly raised in 1997,and the fasting glucose level of the diagnostic criteria of IFG was lowered from 6.1 mmol/L to 5.6 mmol/L in 2003 by ADA. Both IFG and impaired glucose tolerance(IGT) have higher risk of diabetes than normal glucose tolerance, but they also have many different profiles, such as their prevalence in different sex and races, their state of insulin secretion and insulin resistance, their relationship with vascular diseases and the incidence and mortality of vascular diseases. So some actions should be taken for IFG and IGT based on their pathophysiology.
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To assess the usefulness of erythrocyte glycated haemoglobin (HbA1C) as a screening tool to identify those subjects with impaired fasting glycaemia (IFG) who do not have impaired glucose tolerance (IGT) or diabetes mellitus (DM) on a 75 g oral glucose tolerance test (OGTT). Design and methods All subjects undergoing an OGTT had HbA1C measured at baseline. Receiver operator characteristics analysis was used to identify optimal HbA1C cut-off values for diagnosing and excluding IGT and DM.We studied 140 subjects (69 women) with IFG (fasting capillary plasma glucose between 6.1-6.9 mmol/L). Using World Health Organisation criteria, 27 had isolated IFG, 56 had IGT and 57 had DM. HbA1C was higher (P < 0.001) in patients with DM (6.8 +/- 0.93%) when compared with those with IGT (6.3 +/- 0.68%) and isolated IFG (6.2 +/- 0.30%), but HbA1C was similar in those with IGT and isolated IFG. There was no HbA1C cut-off value differentiating isolated IFG from IGT or DM. None of the subjects with isolated IFG had HbA1C concentration of >6.8%, but 76% and 54% subjects with IGT and DM, respectively, had HbA1C of < or =6.8%.HbA1C measurement is of limited value in differentiating isolated IFG, IGT and DM in subjects with IFG. It cannot be used to identify which subjects with IFG do not require an OGTT.
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Prediabetes can be defined by the presence of impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), or glycated haemoglobin (HbA1c) to identify individuals at increased risk of developing type 2 diabetes (T2D). The World Health Organization (WHO, 1999) and the American Diabetes Association (ADA, 2003) utilise different cut-off values for IFG (WHO: 6.1–6.9 mmol/L; ADA: 5.6–6.9 mmol/L) but the same cut-off values for IGT (7.8–11.0 mmol/L). This review investigates whether there are differences in prevalence of IFG, IGT, and combined IFG&IGT between ethnicities, in particular Asian Chinese and European Caucasians. In total, we identified 19 studies using the WHO1999 classification, for which the average proportional prevalence for isolated (i)-IFG, i-IGT, and combined IFG&IGT were 43.9%, 41.0%, and 13.5%, respectively, for Caucasian and 29.2%, 49.4%, and 18.2%, respectively, for Asian. For the 14 studies using ADA2003 classification, the average proportional i-IFG, i-IGT, and combined IFG&IGT prevalences were 58.0%, 20.3%, and 19.8%, respectively, for Caucasian; 48.1%, 27.7%, and 20.5%, respectively, for Asian. Whilst not statistically different, there may be clinically relevant differences in the two populations, with our observations for both classifications indicating that prevalence of i-IFG is higher in Caucasian cohorts whilst i-IGT and combined IFG&IGT are both higher in Asian cohorts.
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It is well established that individuals who have prediabetes either impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) have high risk to develop diabetes. However, it is unclear whether the rate of progression to diabetes is different between these two categories. Lifestyle modification has been recommended for diabetes prevention in these high-risk groups. However, given the differences in their pathophysiology, it is possible that these subtypes of prediabetes condition may have different responses to lifestyle modification. The present review was to summarize the risk of progression to diabetes and the effectiveness of lifestyle intervention for diabetes prevention in individuals who have isolated IGT or isolated IFG or combined. The risk of progression to diabetes is highest in combined IFG and IGT subtype. Individuals who have isolated IFG by the American Diabetes Association criteria (100 to 125 mg/dl) has lower risk of progression to diabetes than those with World Health Organization criteria (110 to 125 mg/dl) and the latter has similar or higher risk of incident diabetes than those with isolated IGT. Lifestyle modification is most effective in individuals with IGT (with or without IFG) but is less effective in those with isolated IFG. In conclusion, The risk of progression to diabetes and the effectiveness of lifestyle intervention for diabetes prevention are disparate between prediabetes subtypes. Given the paucity of diabetes prevention data in individuals with isolated IFG, more studies dedicated to this subtype is required. Keywords: Impaired fasting glucose, Impaired glucose tolerance, Prediabetes, Type 2 diabetes, Lifestyle intervention, Diabetes prevention
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Impaired fasting glucose
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Fasting glucose
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