Fasting hyperglycaemia blunts the reversal of impaired glucose tolerance after exercise training in obese older adults.
ABSTRACT: Lifestyle modification, consisting of exercise and weight loss, delays the progression from prediabetes to type 2 diabetes (T2D). However, no study has determined the efficacy of exercise training on glucose metabolism in the different prediabetes subtypes.Seventy-six older (65.1 ± 0.6 years) obese adults with impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 9) and combined glucose intolerance (IFG + IGT = CGI; n = 22) were compared with normal glucose tolerant (NGT; n = 15) and T2D (n = 18) groups after 12 weeks of exercise training (60 min/day for 5 days/week at ~85% HR(max)). An oral glucose tolerance test was used to assess glucose levels. Insulin sensitivity (IS; euglycaemic hyperinsulinaemic clamp at 40 mU/m(2)/min), ?-cell function (glucose-stimulated insulin secretion corrected for IS), body composition (hydrostatic weighing/computed tomography scan) and cardiovascular fitness (treadmill VO(2) max) were also assessed.Exercise training reduced weight and increased cardiovascular fitness (p < 0.05). Exercise training lowered fasting glucose levels in IFG, CGI and T2D (p < 0.05) and 2-h glucose levels in IGT, CGI and T2D (p < 0.05). However, 2-h glucose levels were not normalized in adults with CGI compared with IGT (p < 0.05). ?-Cell function improved similarly across groups (p < 0.05). Although not statistically significant, IS increased approximately 40% in IFG and IGT, but only 17% in CGI.The magnitude of improvement in glucose metabolism after 12 weeks of exercise training is not uniform across the prediabetes subtypes. Given the high risk of progressing to T2D, adults with CGI may require more aggressive therapies to prevent diabetes.
Project description:To determine if prediabetes phenotype influences improvements in glucose homeostasis with resistance training (RT).Older, overweight individuals with prediabetes (n = 159; aged 60±5 yrs; BMI 33±4 kg/m2) completed a supervised RT program twice per week for 12 weeks. Body weight and composition, strength, fasting plasma glucose, 2-hr oral glucose tolerance, and Matsuda-Defronza estimated insulin sensitivity index (ISI) were assessed before and after the intervention. Participants were categorized according to their baseline prediabetes phenotype as impaired fasting glucose only (IFG) (n = 73), impaired glucose tolerance only (IGT) (n = 21), or combined IFG and IGT (IFG/IGT) (n = 65).Chest press and leg press strength increased 27% and 18%, respectively, following the 12-week RT program (both p<0.05). Waist circumference (-1.0%; pre 109.3±10.3 cm, post 108.2±10.6 cm) and body fat (-0.6%; pre 43.7±6.8%, post 43.1±6.8%) declined, and lean body mass (+1.3%; pre 52.0±10.4 kg, post 52.7±10.7 kg) increased following the intervention. Fasting glucose concentrations did not change (p>0.05) following the intervention. However, 2-hr oral glucose tolerance improved in those with IGT (pre 8.94±0.72 mmol/l, post 7.83±1.11 mmol/l, p<0.05) and IFG/IGT (pre 9.66±1.11mmol/l, post 8.60±2.00 mmol/l) but not in those with IFG (pre 6.27±1.28mmol/l, post 6.33± 1.55 mmol/l). There were no significant changes in ISI or glucose area under the curve following the RT program.RT without dietary intervention improves 2-hr oral glucose tolerance in individuals with prediabetes. However, the improvements in glucose homeostasis with RT appear limited to those with IGT or combined IFG and IGT.ClinicalTrials.gov: NCT01112709.
Project description:<h4>Objectives</h4>To assess the anthropometric characteristics of normoglycaemic individuals who subsequently developed hyperglycaemia, and to evaluate the validity of these measures to predict prediabetes and diabetes.<h4>Design</h4>A community-based prospective cohort study.<h4>Participants</h4>In total, 1885 residents with euglycaemia at baseline from six communities were enrolled.<h4>Setting</h4>Sichuan, southwest China.<h4>Primary outcome measures</h4>The incidences of prediabetes and diabetes were the primary outcomes.<h4>Methods</h4>The waist-to-height ratio (WHtR), body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) of all participants were measured at baseline and during follow-up. A 75?g glucose oral glucose tolerance test was conducted at each survey.<h4>Results</h4>During a median of 3.00 (IQR: 2.92-4.17) years follow-up, the cumulative incidence of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), IFG combined with IGT (IFG+IGT), and newly diagnosed diabetes mellitus (NDDM) were 8.44%, 18.14%, 8.06% and 13.79%, respectively. WHtR, BMI, WC and WHR were significantly different among subjects who subsequently progressed to isolated IFG or IGT, IFG+IGT or NDDM (p<0.05). The anthropometric characteristics of IFG+IGT subjects were similar to those of the NDDM population (p>0.005). All the baseline anthropometric measurements were useful for the prediction of future prediabetes and NDDM (p<0.05). The optimal thresholds for the four measurements were calculated for the prediction of hyperglycaemia, with a WHtR value of 0.52 performing best to identify isolated IFG or IGT, IFG+IGT and NDDM.<h4>Conclusions</h4>Anthropometric measures, especially WHtR, could be used to predict hyperglycaemia 3 years in advance. Distinct from isolated IFG and IGT, the individuals who developed combined IFG+IGT had identical anthropometric profiles to those who progressed to NDDM.
Project description:INTRODUCTION: Single nucleotide polymorphisms (SNPs) in approximately 40 genes have been associated with an increased risk for type 2 diabetes (T2D) in genome-wide association studies. It is not known whether a similar genetic impact on the risk of prediabetes (impaired glucose tolerance [IGT] or impaired fasting glycemia [IFG]) exists. METHODS: In our cohort of 1442 non-diabetic subjects of European origin (normal glucose tolerance [NGT] n?=?1046, isolated IFG n?=?142, isolated IGT n?=?140, IFG+IGT n?=?114), an impact on glucose homeostasis has been shown for 9 SNPs in previous studies in this specific cohort. We analyzed these SNPs (within or in the vicinity of the genes TCF7L2, KCNJ11, HHEX, SLC30A8, WFS1, KCNQ1, MTNR1B, FTO, PPARG) for association with prediabetes. RESULTS: The genetic risk load was significantly associated with the risk for IGT (p?=?0.0006) in a model including gender, age, BMI and insulin sensitivity. To further evaluate potential confounding effects, we stratified the population on gender, BMI and insulin sensitivity. The association of the risk score with IGT was present in female participants (p?=?0.008), but not in male participants. The risk score was significantly associated with IGT (p?=?0.008) in subjects with a body mass index higher than 30 kg/m(2) but not in non-obese individuals. Furthermore, only in insulin resistant subjects a significant association between the genetic load and the risk for IGT (p?=?0.01) was found. DISCUSSION: We found that T2D genetic risk alleles cause an increased risk for IGT. This effect was not present in male, lean and insulin sensitive subjects, suggesting a protective role of beneficial environmental factors on the genetic risk.
Project description:This study investigated the clinical characteristics and associated risk factors of prediabetes in the southwestern region of Korea. A total of 323 subjects from 13 prediabetes studies were included in the data analysis. Subjects with prediabetes were divided into the following subtypes: (1) normal glucose tolerance (NGT) with HbA1c 5.7%-6.4%; (2) isolated impaired fasting glucose (I-IFG); (3) isolated impaired glucose tolerance (I-IGT); and (4) combined I-IFG and I-IGT (C-IFG/IGT). Clinical and biochemical variables were compared among subtypes, and multivariate logistic regression analysis was used to identify risk factors for prediabetes subtypes. The overall proportion of subjects with NGT, I-IFG, I-IGT and C-IFG/IGT was 8.4%, 20.7%, 33.1% and 37.8%, respectively. In men, C-IFG/IGT was the most common subtype, while in women, I-IGT was the most common. The parameters related to dysglycemia, atherosclerosis and liver dysfunction were higher in subjects in the C-IFG/IGT subtype than in other subtypes. Multiple linear regression analysis revealed independent risk factors for increased FPG, 2h-PPG and HbA1c levels. This study identified the clinical features and independent risk factors for prediabetes subtypes.
Project description:AIMS:To identify socioeconomic, behavioral and clinical factors that are associated with prediabetes according to different prediabetes definition criteria. METHODS:Analyses use pooled data of the population-based Cooperative Health Research in the Region of Augsburg (KORA) studies (n?=?5312 observations aged???38 years without diabetes). Prediabetes was defined through either impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or elevated HbA1c according to thresholds of the American Diabetes Association. Explanatory variables were regressed on prediabetes using generalized estimating equations. RESULTS:Mean age was 58.4 years; 50% had prediabetes (33% had IFG, 16% IGT, and 26% elevated HbA1c, 10% fulfilled all three criteria). Age, obesity, hypertension, low education, unemployment, statutory health insurance, urban residence and physical inactivity were associated with prediabetes. Male sex was a stronger risk factor for IFG (OR?=?2.5; 95%-CI: 2.2-2.9) than for IGT or elevated HbA1c, and being unemployed was a stronger risk factor for IGT (OR?=?3.2 95%-CI: 2.6-4.0) than for IFG or elevated HbA1c. CONCLUSIONS:The overlap of people with IFG, IGT and elevated HbA1c is small, and some factors are associated with only one criterion. Knowledge on sociodemographic and socioeconomic risk factors can be used to effectively target interventions to people at high risk for type 2 diabetes.
Project description:<h4>Context</h4>People with prediabetes are at high risk of developing diabetes.<h4>Objective</h4>The objective of this study was to determine the pathogenesis of fasting and postprandial hyperglycemia in prediabetes.<h4>Design</h4>Glucose production, gluconeogenesis, glycogenolysis, and glucose disappearance were measured before and during a hyperinsulinemic clamp using [6,6-(2)H2]glucose and the deuterated water method corrected for transaldolase exchange.<h4>Setting</h4>The study was conducted at the Mayo Clinic Clinical Research Unit.<h4>Participants</h4>Subjects with impaired fasting glucose (IFG)/normal glucose tolerance (NGT) (n = 14), IFG/impaired glucose tolerance (IGT) (n = 18), and normal fasting glucose (NFG)/NGT (n = 16) were studied.<h4>Intervention</h4>A hyperinsulinemic clamp was used.<h4>Outcome measures</h4>Glucose production, glucose disappearance, gluconeogenesis, and glycogenolysis were measured.<h4>Results</h4>Fasting glucose production was higher (P < .0001) in subjects with IFG/NGT than in those with NFG/NGT because of increased rates of gluconeogenesis (P = .003). On the other hand, insulin-induced suppression of glucose production, gluconeogenesis, glycogenolysis, and stimulation of glucose disappearance all were normal. Although fasting glucose production also was increased (P = .0002) in subjects with IFG/IGT, insulin-induced suppression of glucose production, gluconeogenesis, and glycogenolysis and stimulation of glucose disappearance were impaired (P = .005).<h4>Conclusions</h4>Fasting hyperglycemia is due to excessive glucose production in people with either IFG/NGT or IFG/IGT. Both insulin action and postprandial glucose concentrations are normal in IFG/NGT but abnormal in IFG/IGT. This finding suggests that hepatic and extrahepatic insulin resistance causes or exacerbates postprandial glucose intolerance in IFG/IGT. Elevated gluconeogenesis in the fasting state in IFG/NGT and impaired insulin-induced suppression of both gluconeogenesis and glycogenolysis in IFG/IGT suggest that alteration in the regulation of these pathways occurs early in the evolution of type 2 diabetes.
Project description:We developed a multinomial probit model with singular value decomposition for testing a large number of single nucleotide polymorphisms (SNPs) simultaneously, using maximum likelihood estimation and permutation. The method was validated by simulation. We simulated 1000 SNPs, including 9 associated with disease states, and 8 of the 9 were successfully identified. Applying the method to study 32 genes in our Mexican-American samples for association with prediabetes through either impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), we found 3 genes (SORCS1, AMPD1, PPAR) associated with both IGT and IFG, while 5 genes (AMPD2, PRKAA2, C5, TCF7L2, ITR) with the IGT mechanism only and 6 genes (CAPN10, IL4,NOS3, CD14, GCG, SORT1) with the IFG mechanism only. These data suggest that IGT and IFG may indicate different physiological mechanism to prediabetes, via different genetic determinants.
Project description:<h4>Background</h4>We have previously found regional differences in the prevalence of known type 2 diabetes between northeastern and southern Germany. We aim to also provide prevalence estimates for prediabetes (isolated impaired fasting glucose (i-IFG), isolated glucose intolerance (i-IGT), combined IFG and IGT) and unknown type 2 diabetes for both regions.<h4>Methods</h4>Prevalence (95%CI) of prediabetes (i-IFG: fasting glucose 5.6-6.9 mmol/l; i-IGT: 2 h postchallenge glucose 7.8-11.0 mmol/l, oral glucose tolerance test (OGTT), ? 8 h overnight fasting) and unknown diabetes were analyzed in two regional population-based surveys (age group 35-79 years): SHIP-TREND (Study of Health in Pomerania (northeast), 2008-2012) and KORA F4 (Cooperative Health Research in the region of Augsburg (south), 2006-2008). Both studies used similar methods, questionnaires, and identical protocols for OGTT. Overall, 1,980 participants from SHIP-TREND and 2,617 participants from KORA F4 were included.<h4>Results</h4>Age-sex-standardized prevalence estimates (95%CI) of prediabetes and unknown diabetes were considerably higher in the northeast (SHIP-TREND: 43.1%; 40.9-45.3% and 7.1%; 5.9-8.2%) than in the south of Germany (KORA F4: 30.1%; 28.4-31.7% and 3.9%; 3.2-4.6%), respectively. In particular, i-IFG (26.4%; 24.5-28.3% vs. 17.2%; 15.7-18.6%) and IFG+IGT (11.2%; 9.8-12.6% vs. 6.6%; 5.7-7.5%) were more frequent in SHIP-TREND than in KORA. In comparison to normal glucose tolerance, the odds of having unknown diabetes (OR, 95%CI: 2.59; 1.84-3.65) or prediabetes (1.98; 1.70-2.31) was higher in the northeast than in the south after adjustment for known risk factors (obesity, lifestyle).<h4>Conclusions</h4>The regional differences of prediabetes and unknown diabetes are in line with the geographical pattern of known diabetes in Germany. The higher prevalences in the northeast were not explained by traditional risk factors.
Project description:To examine the relationship between hormones involved in bone remodeling and glucose metabolism alterations in prediabetes.Individuals (n = 43) with NGT (BMI = 31.1 ± 1.1 kg/m2) and individuals (n = 79) with impaired glucose regulation (IGR) (BMI = 31.9 ± 1.2 kg/m2) including subjects with IFG, IGT, and IFG-IGT underwent OGTT and DXA. Osteopontin (OPN), osteocalcin (OCN), osteoprotegerin (OPG), and PTH levels were measured at fasting. Beta-cell function was calculated using C-peptide deconvolution. Dynamic indexes of insulin sensitivity were calculated from OGTT. A subgroup underwent to a euglycemic hyperinsulinemic clamp with 3-3H-glucose to estimate the endogenous glucose production (EGP) and insulin-mediated body glucose disposal (TGD/SSPI).OPN was higher in IGR compared to NGT (5.3 ± 0.5 vs. 3.3 ± 0.2 ?g/mL; p = 0.008) and in isolated IGT compared to IFG and IFG-IGT (6.3 ± 0.5 vs. 4.5 ± 0.3 and 5.4 ± 0.5 ?g/mL; p = 0.02). OCN was similar in IFG and NGT but lower in IGT and IFG-IGT compared to NGT (7.2 ± 0.3 and 5.4 ± 0.2 vs. 8.3 ± 0.3 ng/mL; p < 0.01). OPN was positively correlated with HbA1c, fasting and 2 h plasma glucose and PTH. OCN was negatively correlated with body fat, 2 h plasma glucose, insulin and positively correlated with Stumvoll index. OPG correlated with TGD/SSPI (r = - 0.29; p < 0.05), EGP, and hepatic insulin resistance index in IGR (r = 0.51, r = 0.43; p < 0.01). There was no correlation between PTH and insulin sensitivity or Beta-cell function parameters.In prediabetes, hormones known to be involved in bone remodeling may affect glucose metabolism before overt T2DM occurs with tissue-specific mechanisms.
Project description:Objective:To investigate the association between the hypertriglyceridemic waist (HTGW) phenotype and prediabetes in Chinese adults aged 40 years and older. Methods:12757 adults (4101 men and 8656 women) without diabetes or cardiovascular and cerebrovascular diseases, free of using lipid-modified agents, were enrolled in this cross-sectional study. The HTGW phenotype was defined as elevated serum triglyceride concentrations and enlarged waist circumference. A two-hour post 75?g oral glucose tolerance test was performed in all participants. Multiple logistic regression analysis was used to evaluate the relationship of the HTGW phenotype with prediabetes. Results:Individuals with the HTGW phenotype had a higher adjusted odds ratio (OR: 1.70; 95% CI: 1.48-1.95) of prediabetes than those without the phenotype. There existed a strong relationship of the HTGW phenotype with impaired glucose tolerance (IGT) (OR: 1.83; 95% CI: 1.57-2.13), but not with impaired fasting glucose (IFG) (OR: 0.87; 95% CI: 0.65-1.17). Only women with the HTGW phenotype are significantly associated with the combined IFG and IGT (OR: 1.83; 95% CI: 1.28-2.62). Conclusions:The HTGW phenotype was a useful risk indicator and a practical screening tool to benefit in the early diagnosis and intervention for prediabetes, particularly for IGT and the combined IFG and IGT.