Diabetes Prevention Study Research Articles

The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study

Intensive lifestyle interventions can reduce the incidence of type 2 diabetes in people with impaired glucose tolerance, but how long these benefits extend beyond the period of active intervention, and whether such interventions reduce the risk of cardiovascular disease (CVD) and mortality, is unclear. We aimed to assess whether intensive lifestyle interventions have a long-term effect on the risk of diabetes, diabetes-related macrovascular and microvascular complications, and mortality. In 1986, 577 adults with impaired glucose tolerance from 33 clinics in China were randomly assigned to either the control group or to one of three lifestyle intervention groups (diet, exercise, or diet plus exercise). Active intervention took place over 6 years until 1992. In 2006, study participants were followed-up to assess the long-term effect of the interventions. The primary outcomes were diabetes incidence, CVD incidence and mortality, and all-cause mortality. Compared with control participants, those in the combined lifestyle intervention groups had a 51% lower incidence of diabetes (hazard rate ratio [HRR] 0.49; 95% CI 0.33-0.73) during the active intervention period and a 43% lower incidence (0.57; 0.41-0.81) over the 20 year period, controlled for age and clustering by clinic. The average annual incidence of diabetes was 7% for intervention participants versus 11% in control participants, with 20-year cumulative incidence of 80% in the intervention groups and 93% in the control group. Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group. There was no significant difference between the intervention and control groups in the rate of first CVD events (HRR 0.98; 95% CI 0.71-1.37), CVD mortality (0.83; 0.48-1.40), and all-cause mortality (0.96; 0.65-1.41), but our study had limited statistical power to detect differences for these outcomes. Group-based lifestyle interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention. However, whether lifestyle intervention also leads to reduced CVD and mortality remains unclear.

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Exercise training with dietary counselling increases mitochondrial chaperone expression in middle-aged subjects with impaired glucose tolerance

BackgroundInsulin resistance and diabetes are associated with increased oxidative stress and impairment of cellular defence systems. Our purpose was to investigate the interaction between glucose metabolism, antioxidative capacity and heat shock protein (HSP) defence in different skeletal muscle phenotypes among middle-aged obese subjects during a long-term exercise and dietary intervention. As a sub-study of the Finnish Diabetes Prevention Study (DPS), 22 persons with impaired glucose tolerance (IGT) taking part in the intervention volunteered to give samples from the vastus lateralis muscle. Subjects were divided into two sub-groups (IGTslow and IGTfast) on the basis of their baseline myosin heavy chain profile. Glucose metabolism, oxidative stress and HSP expressions were measured before and after the 2-year intervention.ResultsExercise training, combined with dietary counselling, increased the expression of mitochondrial chaperones HSP60 and glucose-regulated protein 75 (GRP75) in the vastus lateralis muscle in the IGTslow group and that of HSP60 in the IGTfast group. In cytoplasmic chaperones HSP72 or HSP90 no changes took place. In the IGTslow group, a significant positive correlation between the increased muscle content of HSP60 and the oxygen radical absorbing capacity values and, in the IGTfast group, between the improved VO2max value and the increased protein expression of GRP75 were found. Serum uric acid concentrations decreased in both sub-groups and serum protein carbonyl concentrations decreased in the IGTfast group.ConclusionThe 2-year intervention up-regulated mitochondrial HSP expressions in middle-aged subjects with impaired glucose tolerance. These improvements, however, were not correlated directly with enhanced glucose tolerance.

Random Plasma Glucose in Serendipitous Screening for Glucose Intolerance: Screening for Impaired Glucose Tolerance Study 2

With positive results from diabetes prevention studies, there is interest in convenient ways to incorporate screening for glucose intolerance into routine care and to limit the need for fasting diagnostic tests. The aim of this study is to determine whether random plasma glucose (RPG) could be used to screen for glucose intolerance. This is a cross-sectional study. The participants of this study include a voluntary sample of 990 adults not known to have diabetes. RPG was measured, and each subject had a 75-g oral glucose tolerance test several weeks later. Glucose intolerance targets included diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose(110) (IFG(110); fasting glucose, 110-125 mg/dl, and 2 h glucose < 140 mg/dl). Screening performance was measured by area under receiver operating characteristic curves (AROC). Mean age was 48 years, and body mass index (BMI) was 30.4 kg/m(2); 66% were women, and 52% were black; 5.1% had previously unrecognized diabetes, and 24.0% had any "high-risk" glucose intolerance (diabetes or IGT or IFG(110)). The AROC was 0.80 (95% CI 0.74-0.86) for RPG to identify diabetes and 0.72 (0.68-0.75) to identify any glucose intolerance, both highly significant (p < 0.001). Screening performance was generally consistent at different times of the day, regardless of meal status, and across a range of risk factors such as age, BMI, high density lipoprotein cholesterol, triglycerides, and blood pressure. RPG values should be considered by health care providers to be an opportunistic initial screening test and used to prompt further evaluation of patients at risk of glucose intolerance. Such "serendipitous screening" could help to identify unrecognized diabetes and prediabetes.

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Prediabetes and its Relationship with Obesity in Mexican Adults: The Mexican Diabetes Prevention (MexDiab) Study

Epidemiological data on impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) based on a representative Mexican sample are not available; thus, the objectives of this study were to determine the prevalence and distribution of IFG and IGT, and to establish its relationship with obesity in Mexican adults. We performed a cross-sectional population-based study on a representative sample of Mexican adults aged 30 to 65 years. Anthropometric measurements of obesity that included waist circumference (WC) and total body fat percentage were collected and the body mass index calculated. All subjects also underwent an oral glucose tolerance test. Diagnosis of glucose metabolism disorders was based on criteria of the American Diabetes Association. Prevalence of IFG, IGT, and IFG+IGT was 24.6%, 8.3%, and 10.3%, respectively. The age-adjusted prevalence of IFG (49.5% and 50.5%), IGT (49.1% and 50.9%), and IFG+IGT (57.3% and 42.7%) was similar in men and women. Prevalence of obesity was 45.9% with predominance in women (48.8% versus 42.1%, P = 0.01). A total of 394 (31.0%) individuals were overweight. Among the 550 prediabetic normal weight subjects, 70 (22.4%), 15 (14.2%), and 7 (5.3%) had IFG, IGT, or IFG+IGT. The odds ratio (OR) between WC and IFG (OR 3.1, CI(95%) 1.4-9.7), IGT (OR 3.2, CI(95%) 1.2-9.1), and IFG+IGT (OR 2.8, CI(95%) 1.3-8.2) was higher than the OR of other measurements of obesity. Prevalence of prediabetes in the Mexican adult population is high. WC is the measure of obesity more strongly associated with metabolic glucose disorders. A high proportion of subjects with normal weight exhibit prediabetes.

Determinants for the Effectiveness of Lifestyle Intervention in the Finnish Diabetes Prevention Study

Intensive lifestyle intervention significantly reduced diabetes incidence among the participants in the Finnish Diabetes Prevention Study. We investigated whether and to what extent risk factors for type 2 diabetes and other baseline characteristics of the study participants modified the effectiveness of the lifestyle intervention. Overweight, middle-aged volunteers with impaired glucose tolerance were randomly assigned to intensive lifestyle intervention (n = 265) or to a control group (n = 257) for a median of 4 years. Diabetes status was ascertained annually with repeated oral glucose tolerance testing. Incidence rates of diabetes and hazard ratios (HRs) comparing the intervention group with the control group were calculated by sex and baseline tertiles of age, BMI, waist circumference, plasma glucose concentration at fasting and 2 h after a glucose load, fasting serum insulin and insulin resistance index, and categories of composite baseline Finnish Diabetes Risk Score (FINDRISC). Interactions between the intervention assignment and baseline risk factors on diabetes risk were analyzed. The intervention was most effective among the oldest individuals (HRs 0.77, 0.49, and 0.36 by increasing age tertiles, respectively; P(interaction) = 0.0130) and those with a high baseline FINDRISC (HRs 1.09, 0.84, 0.34, and 0.22 by increasing risk score category, respectively; P(interaction) = 0.0400). The effect of the intervention on diabetes risk was not modified by other baseline characteristics or risk factors. The FINDRISC may be useful in identifying high-risk groups most likely to benefit from intensive lifestyle intervention to prevent type 2 diabetes.

Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome: The Finnish Diabetes Prevention Study

Single nucleotide polymorphisms (SNPs) in the ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL genes were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2D) in the Finnish Diabetes Prevention Study (DPS). In this study, we determined whether polymorphisms in these genes modified the effect of changes in physical activity (PA) on the risk of T2D in the DPS. Moreover, we assessed whether the polymorphisms modified the effect of changes in PA on changes in measures of body fat, serum lipids, and blood pressure during the first year of the follow-up of the DPS. Overweight subjects with IGT (n = 487) were followed for an average of 4.1 years, and PA was assessed annually with a questionnaire. The interactions of the polymorphisms with changes in total and moderate-to-vigorous PA on the conversion to T2D during the 4.1-year follow-up were assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). Univariate analysis of variance was used to assess interactions on changes in continuous variables during the first year of the follow-up. No interaction between the polymorphisms and PA on the conversion to T2D was found. The Leu72Met (rs696217) polymorphism in GHRL modified the effect of moderate-to-vigorous PA on changes in weight and waist circumference, the −501A/C (rs26802) polymorphism in GHRL modified the effect of total and moderate-to-vigorous PA on change in high-density lipoprotein cholesterol, and the Lys109Arg (rs1137100) polymorphism in LEPR modified the effect of total PA on change in blood pressure. In conclusion, genetic variation may modify the magnitude of the beneficial effects of PA on characteristics of the metabolic syndrome in persons with IGT.

Effect of Lifestyle Intervention on the Occurrence of Metabolic Syndrome and its Components in the Finnish Diabetes Prevention Study

The aim of this secondary analysis of the Finnish Diabetes Prevention Study was to assess the effects of lifestyle intervention on metabolic syndrome and its components. A total of 522 middle-aged overweight men and women with impaired glucose tolerance were randomized into an individualized lifestyle intervention group or a standard care control group. National Cholesterol Education Program criteria were used for the definition of metabolic syndrome. At the end of the study, with a mean follow-up of 3.9 years, we found a significant reduction in the prevalence of metabolic syndrome in the intervention group compared with the control group (odds ratio [OR] 0.62 [95% CI 0.40-0.95]) and in the prevalence of abdominal obesity (0.48 [0.28-0.81]). The results suggest that lifestyle intervention may also reduce risk of cardiovascular disease in the long run.

Exercise and cardiovascular risk reduction: time to update the rationale for exercise?

although it is generally accepted that the promotion of exercise accords with clinical best practice, the anecdotal experience of many primary care physicians, cardiologists, and exercise physiologists is that, even when exercise prescriptions are adhered to, risk factors often fail to demonstrate

Long-term repeatability of measures of early insulin secretion derived from an intravenous glucose tolerance test and conversion from impaired glucose tolerance to diabetes

Aim. We assessed the long-term repeatability of the acute insulin response (AIR) and sensitivity index (SI) derived from the frequently sampled intravenous glucose tolerance test (FSIGT).Methods. An FSIGT was performed in 20 women who participated in a 6.5-month rye- and wheat-bread intervention trial, 70 men and women with impaired fasting glycaemia (IFG) or impaired glucose tolerance (IGT) who participated in the Genobin study, and 81 men and women with IGT who participated in the Finnish Diabetes Prevention Study (DPS).Results. The correlation of AIR and SI at base-line with respective values after the 6.5–8.5-month trials was 0.86–0.88 and 0.71–0.84, and before and after 4 years in the DPS substudy, 0.86 and 0.53. In multivariate analyses, AIR (relative risk for a 1-SD change, 0.67; 95% confidence intervals 0.46–0.97) predicted the conversion from IGT to diabetes in the DPS substudy.Conclusion. AIR is highly repeatable even after 4 years of follow-up. The long-term repeatability of SI is moderate. Our findings emphasize the importance of impaired early insulin secretion in the transition from IGT to diabetes, and the high degree of tracking of measures of early insulin secretion derived from the FSIGT.

SNPs in PPARG Associate with Type 2 Diabetes and Interact with Physical Activity

To study the associations of seven single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor gamma (PPARG) gene with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D), and the interactions of the SNPs with physical activity (PA). Overweight individuals with IGT who participated in the Finnish Diabetes Prevention Study (DPS) (N = 479) were followed, on average, 4.2 yr. PA was assessed yearly with a 12-month validated questionnaire. In Cox regression analyses, the rare alleles of rs17036314 and rs1801282 (Pro12Ala) predicted conversion to T2D (P = 0.038 and 0.037, respectively), but only rs17036314 predicted T2D after adjustment for baseline fasting glucose (P = 0.030). The change in the total amount of PA, stratified by median, modified the association of rs17036314 and rs1801282 with the risk of T2D during the intervention (P = 0.002 and 0.031, respectively, for interaction between PA change and genotype); an increase in PA seemed to remove the effect of the risk alleles. The distinct rs1152003 polymorphism interacted with the study group on the conversion to T2D (P = 0.027) and tended to increase the risk of T2D in the intervention group (P = 0.050). No interaction between rs1152003 and the change in PA was found. The rs17036314, rs1801282 (Pro12Ala), and rs1152003 were associated with the risk of T2D in the DPS. Increased PA seemed to decrease the effect of the risk alleles of rs17036314 and rs1801282 on the conversion to T2D. The effect of rs1152003 was modified by other lifestyle changes or the lifestyle intervention as a whole.

Diabetes experts' reasoning about diabetes prevention studies: a questionnaire survey

BackgroundPresentation of results of diabetes prevention studies as relative risk reductions and the use of diagnostic categories instead of metabolic parameters leads to overestimation of effects on diabetes risk. This survey examines to what extent overestimation of diabetes prevention is related to overestimation of prevention of late complications.MethodsParticipants of two postgraduate courses in clinical diabetology in Austria (n = 69) and Germany (n = 31) were presented a questionnaire with 8 items at the beginning of the meetings. All 100 questionnaires were returned with 92 filled in completely. Participants were asked 1) to rate the importance of differently framed results of prevention studies and, for comparison, of the United Kingdom Prospective Diabetes Study (UKPDS), 2) to estimate to what extent late complications could be prevented by the achieved reductions in diabetes risk or HbA1c values, respectively.ResultsPrevention of diabetes by 60% was considered important by 84% of participants and 35% thought that complications could be prevented by ≥ 55%. However, if corresponding HbA1c values were presented (6.0% versus 6.1%) only 19% rated this effect important, and 12% thought that late complications could be prevented by ≥ 55%. The difference in HbA1c of 0.9% over 10 years in the UKPDS was considered important by 75% of participants and 16% thought that complications ('any diabetes related endpoint') were reduced by ≥ 55% (correct answer <15% by 20% participants).ConclusionThe novel key message of this study is that the misleading reporting of diabetes prevention studies results in overestimation of effects on late complications.

Effects of gender and height on the oral glucose tolerance test: the isfahan diabetes prevention study.

Impaired fasting glucose (IFG) is more prevalent in men, whereas impaired glucose tolerance (IGT) is more prevalent in women. To determine whether gender difference in the prevalence of glucose intolerance is related to height. A cross-sectional study of 2,368 first-degree relatives (FDR) of patients with type 2 diabetes was conducted between years 2003 to 2005. All participants (614 men and 1754 women) were in the age range 30-60 years, and were FDR of consecutive patients from outpatient clinics at Isfahan Endocrine and Metabolism Research Centre, Iran. All subjects underwent a standard 75 g 2-h oral glucose tolerance test (OGTT). Weight, height, waist and hip circumference, and glycated haemoglobin were also measured. IGT was more common amongst women (OR 0.66; 95% CI 0.51, 0.87),whereas diabetes (OR 1.31; 95% CI 0.96, 1.78), and IFG (OR 1.41; 95% CI 1.10, 1.80) was more common amongst men. Women had a lower mean fasting plasma glucose (FPG) (p < 0.001), but showed higher 2hPG, and FPG-2hPG increase (p < 0.001). The gender difference in mean 2hPG and FPG-2hPG increase, was not evident after adjustment for height. Negative correlation to height was observed in 2hPG and FPG-2hPG increase, both in men and women (p < 0.001), but height showed little association with FPG. Women had higher mean 2hPG and FPG-2hPG increase, but showed a lower FPG level than men. The inverse association between height and 2hPG and FPG-2hPG increase may be explained by gender difference.

Do Group Education Classes Targeting Impaired Glucose Tolerance (IGT) Population Improve the 75 gram Oral Glucose Tolerance Test (OGTT)

The primary purpose of this study is to determine if the MSH IGT class can assist patients to make healthy lifestyle changes that will decrease their risk of developing type 2 diabetes. Outcome measures included: 2 hour 75 gram Oral Glucose Tolerance Test (OGTT), weight, waist circumference and increased activity. The two pioneering studies, (Diabetes Prevention Program and the Finnish Diabetes Prevention Study) in the area of IGT demonstrated that diabetes can be prevented/delayed if lifestyle changes occur, and the 75 gram OGTT results reverts back to normal value.

Prevention of Type 2 diabetes: fact or fiction?

The growing prevalence of Type 2 diabetes with its high morbidity and excess mortality is imposing a heavy burden on healthcare systems. Because of the magnitude of the problem, obviating diabetes has been a long-standing dream. In the last decade, a number of intervention strategies have been shown to be effective for the prevention of diabetes in high-risk populations with prediabetes. Seven studies have now confirmed that lifestyle modifications, including weight-reducing diets and exercise programs, are very effective in precluding or delaying Type 2 diabetes in high-risk populations with impaired glucose tolerance (IGT). Two major trials are the Diabetes Prevention Study (n = 522) from Finland and the Diabetes Prevention Program (n = 3234) from the US. Both studies have shown that intensive lifestyle intervention could reduce the progression of IGT to diabetes by 58%. Furthermore, four currently-available drugs have been established as being effective in preventing diabetes in subjects with prediabetes. The Diabetes Prevention Program revealed that metformin 850 mg b.i.d. reduced the risk of diabetes by 31%. The STOP-NIDDM (Study To Prevent Non-Insulin-Dependent Diabetes Mellitus) trial (n = 1429) showed that acarbose 100 mg t.i.d. with meals decreased the incidence of diabetes by 36% when the diagnosis was based on 2 oral glucose tolerance tests. The XENDOS (Xenical in the Prevention of Diabetes in Obese Subjects) study examined the use of orlistat, an antiobesity drug, as an adjunct to an intensive lifestyle modification program in obese non-diabetic subjects. Orlistat treatment resulted in a 37% decline in the development of diabetes. More recently, the DREAM (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication) study (n = 5269) demonstrated that rosiglitazone at 8 mg once/day in subjects with prediabetes (IGT and/or impaired fasting glucose) was effective in reducing the risk of diabetes by 60%. It can be concluded that Type 2 diabetes can be prevented or delayed through lifestyle modifications and/or pharmacologic interventions. This is a fact.

Exercise Training for Diabetes: The “Strength” of the Evidence

Editorials18 September 2007Exercise Training for Diabetes: The “Strength” of the EvidenceWilliam E. Kraus, MD and Benjamin D. Levine, MDWilliam E. Kraus, MDFrom Duke University Medical Center, Durham, NC 27710, and Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas and University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75231.Search for more papers by this author and Benjamin D. Levine, MDFrom Duke University Medical Center, Durham, NC 27710, and Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas and University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75231.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-147-6-200709180-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Exercise is an essential component in the treatment of diabetes mellitus. Lifestyle factors affect the prevention, development, and treatment of diabetes mellitus and its close relation, the metabolic syndrome (1). The Finnish Diabetes Prevention Study (2) and the Diabetes Prevention Program (3) tested lifestyle interventions that included a physical activity program. Both studies showed the power of exercise, nutrition, and weight loss to prevent diabetes mellitus in at-risk individuals.However, exercise comes in several flavors, and the clinician should think critically about the effects of different types of exercise training. It is useful to think of exercise training as a ...

Endocrine-Related Resources from the National Institutes of Health

Endocrine-Related Resources from the National Institutes of Health

Increased physical activity is a cornerstone in the prevention of type 2 diabetes in high-risk individuals

To the Editor: We read with interest the review by Yates et al. [1] and the corresponding editorial by Carnethon [2]. We agree with most of the interpretations and conclusions, but feel that the authors may have underestimated the current evidence on the role of physical activity in the prevention of type 2 diabetes in individuals with impaired glucose tolerance. The only trial published thus far on the prevention of type 2 diabetes that has included a separate arm of exercise only is the Da Qing IGT and Diabetes Study [3]. We agree with Yates et al. [1] that physical activity was poorly documented in the Chinese study. Therefore, we disagree with their conclusion that higher levels of physical activity at baseline are likely to explain why the rate of type 2 diabetes development was lower in the exercise arm than in the control arm. Rather, it only raises the possibility. Yates et al. [1] stated that in the trials reported, only small changes in physical activity were found, also referring to the 9 min/day increase in moderate to vigorous physical activity reported in the intervention group of the Finnish Diabetes Prevention Study (DPS) [4]. We do not agree that 1 h/week of moderate to vigorous physical activity is insubstantial. Quite the opposite—we found a shift in physical activity from inactive to active in the intervention group of the DPS. The percentage of sedentary individuals (<1 h/week of moderate to vigorous physical activity) decreased from 37 to 15%, and those engaging in at least 2.5 h/week increased from 41 to 62% [4]. This is likely to result in substantial health benefits. We relied on self-reported data on physical activity, collected through a validated questionnaire. The rapid development of physical activity monitors will make objective measurement of physical activity more feasible in future trials. Yates et al. [1] interpreted the Finnish DPS data to suggest that it provided evidence for a protective effect only of large changes in physical activity. We also reported that individuals who engaged in at least 2.5 h/week of brisk walking or other forms of moderate to vigorous physical activity were 44–69% less likely to develop diabetes than Diabetologia (2007) 50:2607–2608 DOI 10.1007/s00125-007-0805-y

Physical activity modifies the effect of SNPs in theSLC2A2(GLUT2) andABCC8(SUR1) genes on the risk of developing type 2 diabetes

Single nucleotide polymorphisms (SNPs) in two genes regulating insulin secretion, SLC2A2 (encoding GLUT2) and ABCC8 (encoding SUR1), were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in the Finnish Diabetes Prevention Study (DPS). We determined whether physical activity (PA), assessed annually with a questionnaire, modified the association of SNPs in SLC2A2 and ABCC8 with the conversion to T2D in the combined intervention and control groups of the DPS. Finnish overweight subjects with IGT (N = 479) were followed for an average of 4.1 yr. The interaction of the SNPs with the change in PA on the conversion to T2D was assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). The carriers of the common homozygous genotype of rs5393, rs5394, or rs5404 of SLC2A2 and rs3758947 of ABCC8 who were in the lower third of the change in moderate-to-vigorous PA during the follow-up had a 2.6- to 3.7-fold increased risk of developing T2D compared with the upper third, whereas the rare allele carriers seemed to be unresponsive to changes in moderate-to-vigorous PA (for the interaction of genotype with change in PA, P = 0.022-0.027 for the SNPs in SLC2A2, and P = 0.007 for rs3758947). We conclude that moderate-to-vigorous PA may modify the risk of developing T2D associated with genes regulating insulin secretion (SLC2A2, ABCC8) in persons with IGT.