Finnish Diabetes Prevention Study Research Articles

Long-term cumulative incidence of clinically diagnosed retinopathy in the Finnish Diabetes Prevention Study.

Lifestyle intervention reduces the incidence of type 2 diabetes (T2D) in people with impaired glucose tolerance. To find out whether participation in the earlier lifestyle intervention had an effect on the occurrence of clinically diagnosed retinopathy during a median of 22 years of follow-up time. The study included 505 individuals from the Finnish Diabetes Prevention Study (DPS) (mean 55, range 40-64 years at the onset of the study) with impaired glucose tolerance who were originally randomized into the intervention (weight loss, healthy diet and physical activity (N=257) and usual care control groups (N=248). The median follow-up was 22 years. Clinical retinopathy diagnoses were obtained from the Finnish national hospital Care Register for Health. Data on glycemic parameters, serum lipids and blood pressure were available from both the intervention (median 4 years) and post-intervention period (until the year 7). No significant difference was found in the cumulative incidence of clinically diagnosed diabetic retinopathy between the original intervention (N=23, 8.9%) and control groups (N=19, 7.7%) during the extended follow-up (Odds ratio: 1.15, 95% confidence interval: 0.61-2.21). A higher cumulative HbA1c was significantly associated with a higher risk of retinopathy (Hazard ratio 1.4; 1.02-1.88, 95% posterior interval, adjusted for group, age and sex). Furthermore, the incidence of retinopathy diagnosis was numerically more common among individuals who had developed diabetes during the follow-up (33/349) compared with those who had not (9/156), however, the comparison was not statistically significant (Odds ratio: 1.86, 95% confidence interval: 0.89-4.28, adjusted for group, age and sex). A higher cumulative HbA1c was significantly associated with a higher risk of retinopathy. No evidence was found for a beneficial effect of a 4-year lifestyle intervention on the long-term occurrence of clinically diagnosed retinopathy during a median of 22-year follow-up.

Genetic risk of type 2 diabetes modifies the association between lifestyle and glycemic health at 5 years postpartum among high-risk women

IntroductionLifestyle interventions are effective in preventing type 2 diabetes, but genetic background may influence the individual response. In the Finnish gestational diabetes prevention study, RADIEL, lifestyle intervention during pregnancy and...

CXADR polymorphism rs6517774 modifies islet autoimmunity characteristics and exhibits sex disparity.

Enteroviral infections have been linked to the development of islet autoimmunity (IA) and type 1 diabetes (T1D), and the coxsackie and adenovirus receptor (CXADR) is one of the ligands used by adenoviruses and enteroviruses for cell internalization. Two CXADR single nucleotide polymorphisms (SNPs), rs6517774 and rs2824404, were previously associated with an increased susceptibility to IA in the international TEDDY study (The Environmental Determinants of Diabetes in the Young). This study aimed to replicate the results by genotyping 2886 children enrolled in the Finnish Diabetes Prediction and Prevention study (DIPP). In our preliminary analysis of the SNPs' allelic distributions, we could not find any association with IA susceptibility. However, a stratified analysis revealed a sex disparity, since the allelic distribution of rs6517774 was different when comparing autoantibody positive females with males; a difference not seen in healthy subjects. By using HLA risk groups and sex as covariates, a Cox regression survival analysis found that the rs6517774 (A/G) SNP was associated with a lower age at seroconversion in females (Female*rs6517774-AA; HR = 1.53, p = 0.002), while introducing a protective effect in males. Accordingly, we propose that rs6517774 alters IA characteristics by modifying the age at seroconversion in a sex-dependent manner. In light of this observation, rs6517774 now joins a limited set on SNPs found to introduce sex-dependent risk effects on the age at IA initiation.

Eating behavior dimensions and 9-year weight loss maintenance: a sub-study of the Finnish Diabetes prevention study

BackgroundBehavioral processes through which lifestyle interventions influence risk factors for type 2 diabetes (T2DM), e.g., body weight, are not well-understood. We examined whether changes in psychological dimensions of eating behavior during the first year of lifestyle intervention would mediate the effects of intervention on body weight during a 9-year period.MethodsMiddle-aged participants (38 men, 60 women) with overweight and impaired glucose tolerance (IGT) were randomized to an intensive, individualized lifestyle intervention group (n = 51) or a control group (n = 47). At baseline and annually thereafter until nine years body weight was measured and the Three Factor Eating Questionnaire assessing cognitive restraint of eating with flexible and rigid components, disinhibition and susceptibility to hunger was completed. This was a sub-study of the Finnish Diabetes Prevention Study, conducted in Kuopio research center.ResultsDuring the first year of the intervention total cognitive (4.6 vs. 1.7 scores; p < 0.001), flexible (1.7 vs. 0.9; p = 0.018) and rigid (1.6 vs. 0.5; p = 0.001) restraint of eating increased, and body weight decreased (−5.2 vs. −1.2 kg; p < 0.001) more in the intervention group compared with the control group. The difference between the groups remained significant up to nine years regarding total (2.6 vs. 0.1 scores; p = 0.002) and rigid restraint (1.0 vs. 0.4; p = 0.004), and weight loss (−3.0 vs. 0.1 kg; p = 0.046). The first-year increases in total, flexible and rigid restraint statistically mediated the impact of intervention on weight loss during the 9-year study period.ConclusionsLifestyle intervention with intensive and individually tailored, professional counselling had long-lasting effects on cognitive restraint of eating and body weight in middle-aged participants with overweight and IGT. The mediation analyses suggest that early phase increase in cognitive restraint could have a role in long-term weight loss maintenance. This is important because long-term weight loss maintenance has various health benefits, including reduced risk of T2DM.

Longitudinal Branched-Chain Amino Acids, Lifestyle Intervention, and Type 2 Diabetes in the Finnish Diabetes Prevention Study.

ContextCirculating branched-chain amino acids (BCAAs) are associated with the risk of type 2 diabetes (T2D).ObjectiveWe examined to what extent lifestyle intervention aiming to prevent T2D interacts with this association and how BCAA concentrations change during the intervention.MethodsWe computed trajectory clusters by k-means clustering of serum fasting BCAAs analyzed annually by mass spectrometry during a 4-year intervention. We investigated whether baseline BCAAs, BCAA trajectories, and BCAA change trajectories predicted T2D and whether BCAAs predicted T2D differently in the intervention (n = 198) and control group (n = 196).ResultsElevated baseline BCAAs predicted the incidence of T2D in the control group (hazard ratio [HR] 1.05 per 10 μmol/L, P = 0.01), but not in the intervention group. BCAA concentration decreased during the first year in the whole cohort (mean −14.9 μmol/L, P < 0.001), with no significant difference between the groups. We identified 5 BCAA trajectory clusters and 5 trajectory clusters for the change in BCAAs. Trajectories with high mean BCAA levels were associated with an increased HR for T2D compared with the trajectory with low BCAA levels (trajectory with highest vs lowest BCAA, HR 4.0; P = 0.01). A trajectory with increasing BCAA levels had a higher HR for T2D compared with decreasing trajectory in the intervention group only (HR 25.4, P < 0.001).ConclusionLifestyle intervention modified the association of the baseline BCAA concentration and BCAA trajectories with the incidence of T2D. Our study adds to the accumulating evidence on the mechanisms behind the effect of lifestyle changes on the risk of T2D.

Abstract 156: Nutrition therapy: Evaluating relevant interactions for therapeutic success

Background: Clinical nutrition services focus on calories and when a patient looses weight, it may result in both fat and protein loss. There is a lacunae in incorporating anthropometric data as part of nutritional services.Aim: To evaluate nutritional therapy in Diabetes with anthropometric data beyond weight.Materials and Methods: A total number of 847 diabetes patients in age group 35-71 years referred to Division of Nutrition, St. John's Medical College Hospital, Bangalore were recruited from 2015 to 2017. Anthropometric measurements including Body-Mass-Index (BMI), Waist-circumference (WC), Waist–Hip Ratio (WHR), Mid-ArmCircumference (MAC) were carried out on the patients on the first visit and subsequently on every other visit. A 24-hour dietary and physical activity recall was done by a nutritionist and a specific individualised plan was provided based on current intake. Wherever applicable paired ‘t’ test & univariate regression analysis were carried out between anthropometric, biochemical and dietary variables. The mean follow up was 12 months.Results: There was a significant positive association between BMI, percent body fat and WC, but not with WHR. On 24-hour dietary recall done during follow up, individuals in all the BMI groups consumed diets that closely matched international dietary recommendations for diabetes in terms of fibre intake, carbohydrate:protein:fat ratio. Patient's blood glucose profiles improved with a decrease in fat intake, without significant weight-loss. The mid-arm-circumference remained same through the study period.Conclusion: Clinical nutrition programs should utilize anthropometric data like WC & MAC along with dietary recall. Appropriate counselling with balanced diet beyond calories should be provided to achieve a decrease in fat mass without a decrease in mid-arm-circumference to maintain the protein mass. This data compares favourably with the Finnish Diabetes Prevention Study (DPS).

Patient-Centered Care for Obesity: How Health Care Providers Can Treat Obesity While Actively Addressing Weight Stigma and Eating Disorder Risk

Patient-Centered Care for Obesity: How Health Care Providers Can Treat Obesity While Actively Addressing Weight Stigma and Eating Disorder Risk

Serum Levels of Plasmalogens and Fatty Acid Metabolites Associate with Retinal Microangiopathy in Participants from the Finnish Diabetes Prevention Study.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes, and retinal microaneurysms (MA) are one of the first detected abnormalities associated with DR. We recently showed elevated serum triglyceride levels to be associated with the development of MA in the Finnish Diabetes Prevention Study (DPS). The purpose of this metabolomics study was to assess whether serum fatty acid (FA) composition, plasmalogens, and low-grade inflammation may enhance or decrease the risk of MA. Originally, the DPS included 522 individuals (mean 55 years old, range 40–64 years) with impaired glucose tolerance who were randomized into an intervention (n = 265) or control group (n = 257). The intervention lasted for a median of four years (active period), after which annual follow-up visits were conducted. At least five years after stopping the intervention phase of DPS, participants classified as MA negative (n = 115) or MA positive (n = 51) were included in the current study. All these participants were free of diabetes at baseline (WHO 1985) and had high-sensitive C-reactive protein (hs-CRP), serum FA composition, and selected lipid metabolites measured during the active study period. Among the markers associated with MA, the serum plasmalogen dm16:0 (p = 0.006), the saturated odd-chain FA 15.0 (pentadecanoic acid; p = 0.015), and omega-3 very long-chain FAs (p < 0.05) were associated with a decreased occurrence of MA. These associations were independent of study group and other risk factors. The association of high serum triglycerides with the MA occurrence was attenuated when these MA-associated serum lipid markers were considered. Our findings suggest that, in addition to n-3 FAs, odd-chain FA 15:0 and plasmalogen dm16:0 may contribute to a lower risk of MA in individuals with impaired glucose tolerance. These putative novel lipid biomarkers have an association with MA independently of triglyceride levels.

Transgenerational effects of maternal obesity and gestational diabetes on offspring body composition and left ventricle mass: the Finnish Gestational Diabetes Prevention Study (RADIEL) 6‐year follow‐up

To investigate the influence of maternal adiposity and gestational diabetes on offspring body composition and left ventricle mass in early childhood. The observational follow-up study included 201 mother-child pairs, a sub-cohort from the Finnish Gestational Diabetes Prevention Study, who were recruited 6.1 ± 0.5 (mean ± SD) years postpartum, aiming for an equal number of mothers with and without gestational diabetes. Maternal pre-pregnancy BMI (mean ± SD; 30.5 ± 5.6 kg/m2 ) was associated with child body fat percentage [0.26 (95% CI; 0.08, 0.44)% increase in child body fat per 1 kg/m2 increase in pre-pregnancy BMI of mothers with obesity] and was reflected in child BMI Z-score (mean ± SD; 0.45 ± 0.93). Left ventricle mass, left ventricle mass index and left ventricle mass Z-score were not associated with gestational diabetes, pre-pregnancy BMI or child body fat percentage. After adjusting for child sex, body fat percentage, systolic blood pressure, pre-pregnancy BMI and maternal lean body mass, left ventricle mass increased by 3.08 (95% CI; 2.25, 3.91) g for each 1 kg in child lean body mass. Left ventricle mass at 6 years of age is determined predominantly by lean body mass. Maternal pre-gestational adiposity is reflected in child, but no direct association between left ventricle mass and child adiposity or evidence of left ventricle mass foetal programming related to gestational diabetes and maternal adiposity was observed in early childhood.

Effect of maternal lifestyle intervention on metabolic health and adiposity of offspring: Findings from the Finnish Gestational Diabetes Prevention Study (RADIEL)

AimTo assess in women at high risk of gestational diabetes mellitus (GDM) the effect of a lifestyle intervention on the metabolic health of their offspring around 5 years after delivery. MethodsFor the original Finnish gestational diabetes prevention study (RADIEL), 720 women with a prepregnancy body mass index (BMI)≥30kg/m2 and/or previous GDM were enrolled before or during early pregnancy and allocated to either an interventional (n=126) or conventional (n=133) care group. The present 5-year follow-up substudy assessed the metabolic health outcomes of their offspring. Age- and gender-standardized residuals of metabolic health components (waist circumference, mean arterial pressure, high-density lipoprotein and triglyceride levels, and fasting insulin/glucose ratio) were also combined to determine the accumulation of metabolic effects. Body composition was assessed by electrical bioimpedance. ResultsOffspring of women in the intervention group had a less optimal metabolic profile after the 5-year follow-up compared with offspring in the usual care group (P=0.014). This difference in metabolic health was primarily related to lipid metabolism, and was more prominent among boys (P=0.001) than girls (P=0.74). Neither GDM, gestational weight gain, prepregnancy BMI, offspring age nor timing of randomization (before or during pregnancy) could explain the detected difference, which was also more pronounced among the offspring of GDM pregnancies (P=0.010). Offspring body composition was similar in both groups (P>0.05). ConclusionThe lifestyle intervention aimed at GDM prevention was associated with unfavourable metabolic outcomes among offspring at around 5 years of age.

902-P: Effectiveness of Evidence-Based Diabetes Prevention Program in Adults at High Risk of Developing Type 2 Diabetes: A Systematic Review and Meta-analysis

Objective: This systematic review aimed to establish a specific evidence-base of diabetes prevention programs for adults at high risk of developing type 2 diabetes (T2D) based on either the Diabetes Prevention Program (DPP) or the Finnish Diabetes Prevention Study (DPS). Methods: The bibliographic databases: Medline, Ovid, Embase, CINAHL, Scopus, Web of Science, Joanna Brigg Institute Library, Cochrane Central Register of Controlled Trials, and grey literature were searched for published articles in the English language from January 1996 to December 2018. This review included only RCTs conducted in community settings focusing on adults at high risk of T2D, utilizing an intervention based on either the DPP or DPS and measuring the incidence of T2D as an outcome. Results: Of 4,964 identified records, eight studies met all inclusion criteria and were suitable for meta-analysis. The meta-analysis revealed positive effects of programs based on either DPP or DPS on prevention T2D in adults at high risk. The pooled incidence rate of T2D in the intervention group was 47% lower than those in the control group (95% CI 9%, 69%). Attending lifestyle change program achieved a pooled mean weight loss of 2.10 kg (95% CI -3.45, -0.74) which was significantly higher than those of the control group. Data in physical activity, dietary and HbA1c were not commonly reported. Although the feasibility of the prevention program was established, this review found a lack of data in enablers and barriers in implementing a diabetes prevention program. Conclusion: The effectiveness of T2D prevention program based on either the DPP or DPS delivered in community settings is evidenced, and the reduction in cumulative incidence of T2D was reported. Nonetheless, further research on enables and barriers associated with increasing physical activity and improving healthy eating is warranted to help sustain the optimal outcomes of the pragmatic diabetes prevention program. Disclosure K.H. Wechkunanukul: None. F. Benton: None. J. McGill: None. S. Ullah: None.

Overview of Type 2 Diabetes Prevention Recommendations

The article reviews international recommendations for the prevention of type 2 diabetes. The recommendations are based on the results of several large-scale randomized clinical trials, including the Diabetes Prevention Program (DPP) and (DPPOS), the Finnish Diabetes Prevention Study (DPS) and the Diabetes Prevention Study (DaQing study), which demonstrate that lifestyle changes / behavioral therapy and the use of metformin are very effective methods of primary prevention of diabetes.According to the conclusions from the DPP study: the most effective way of primary prevention is an intensive lifestyle change, which mainly consists of reducing body weight> 7%, following a strict low-calorie diet with fat restriction and moderate physical activity lasting for 150 minutes per week. Patients' compliance (especially for a long time) with measures to intensively change their lifestyle is low. In a social environment, the implementation of this method is extremely difficult. It was noted that metformin proved to be as effective as intensive lifestyle modification in individuals under the age of 45 years with severe obesity (BMI ≥ 35 kg / m2). Thus, the author concludes: the patients' commitment to a set of measures aimed at changing their lifestyle is low. Metformin therapy leads to a stable reduction in the risk of diabetes. In addition, metformin, in accordance with the findings of the UKPDS study, reduces the risk of development of cardiovascular disease.

Associations of serum indolepropionic acid, a gut microbiota metabolite, with type 2 diabetes and low-grade inflammation in high-risk individuals

We recently reported using non-targeted metabolic profiling that serum indolepropionic acid (IPA), a microbial metabolite of tryptophan, was associated with a lower likelihood of developing type 2 diabetes (T2D). In the present study, we established a targeted quantitative method using liquid chromatography with mass spectrometric detection (HPLC-QQQ-MS/MS) and measured the serum concentrations of IPA in all the participants from the Finnish Diabetes Prevention Study (DPS), who had fasting serum samples available from the 1-year study follow-up (n = 209 lifestyle intervention and n = 206 control group). Higher IPA at 1-year study was inversely associated with the incidence of T2D (OR [CI]: 0.86 [0.73–0.99], P = 0.04) and tended to be directly associated with insulin secretion (β = 0.10, P = 0.06) during the mean 7-year follow-up. Moreover, IPA correlated positively with dietary fiber intake (g/day: r = 0.24, P = 1 × 10−6) and negatively with hsCRP concentrations at both sampling (r = − 0.22, P = 0.0001) and study follow-up (β = − 0.19, P = 0.001). Thus, we suggest that the putative effect of IPA on lowering T2D risk might be mediated by the interplay between dietary fiber intake and inflammation or by direct effect of IPA on β-cell function.

Serum adiponectin/Ferritin ratio in relation to the risk of type 2 diabetes and insulin sensitivity

AimsBody iron inhibits the metabolism of adiponectin, an insulin sensitizing adipokine. We investigated the relationships of baseline and average of 4-year change in values of serum adiponectin (sA), serum ferritin (sF) and sA/sF ratio on type 2 diabetes (T2D) risk and insulin sensitivity (Matsuda ISI) and secretion (disposition index; DI30). MethodsProspective analyses were conducted in participants with impaired glucose tolerance of the Finnish Diabetes Prevention Study (n = 516) recruited in 1993–1998. Cox and linear regression analyses were used to investigate the associations of sA, sF and sA/sF ratio, as continuous variables, with incident T2D, Matsuda ISI, and DI30. ResultsDuring the mean follow-up of 8.2 years, 157 incident T2D cases occurred (intervention group, n = 65 and control group, n = 92). In adjusted models, baseline sA and sA/sF ratio were inversely associated with T2D risk (HR = 0.49, 95% CI 0.31–0.76, P = 0.002 and HR = 0.83, 95% CI 0.70–0.99, P = 0.044, respectively). Furthermore, a direct association was observed with Matsuda ISI (β=0.13, 95% CI 0.03–0.22, P = 0.009, for sA and β=0.04, 95% CI 0.01–0.07, P = 0.035, for sA/sF ratio) during the average 4-year follow-up. The changes in sA and sA/sF ratio were also inversely associated with T2D risk (HR = 0.36, 95% CI 0.20–0.63, P < 0.001 and HR = 0.76, 95% CI 0.62–0.92, P = 0.006, respectively), and directly with Matsuda ISI (β=0.27, 95% CI 0.17–0.38, P < 0.001, for sA and β=0.07, 95% CI 0.03–0.11, P < 0.001, for sA/sF ratio). No consistent associations were found with DI30. ConclusionsBaseline levels and changes during the follow-up in sA and sA/sF ratio are related to T2D risk and insulin sensitivity.

Reducing the Risk of Developing Diabetes.

Reducing the Risk of Developing Diabetes.

Diabetes prevention in the real world: Insights from the JDPP and J-DOIT1.

Type 2 diabetes (T2D) is associated with increased risks of morbidity and mortality. Diabetes prevention is an urgent issue in Japan. The Finnish Diabetes Prevention Study and US Diabetes Prevention Program revealed that intensive lifestyle intervention can prevent or delay the development of T2D in high‐risk populations. Translational research varies in hospitals, primary care, communities, the workplace, and other settings. Translational research is feasible but less effective. There have been no long‐term follow‐ups. The outcome of the studies was mainly weight changes. The Japan Diabetes Prevention Program (JDPP) is a trial to test the efficacy of a lifestyle intervention program, which carried out in a primary healthcare setting using existing resources. The Japan Diabetes Outcome Trial‐1 (J‐DOIT1) is a nationwide telephone‐delivered lifestyle intervention in a real‐world setting. This review will focus on the effectiveness of a diabetes prevention program (recruitment, target population, method of intervention, and evaluation) in the real world and insights from the JDPP and J‐DOIT1.

Alterations in fatty acid metabolism in response to obesity surgery combined with dietary counseling

Background:The effects of obesity surgery on serum and adipose tissue fatty acid (FA) profile and FA metabolism may modify the risk of obesity-related diseases.Methods:We measured serum (n=122) and adipose tissue (n=24) FA composition and adipose tissue mRNA expression of genes regulating FA metabolism (n=100) in participants of the Kuopio Obesity Surgery Study (KOBS, age 47.2±8.7 years, BMI 44.6±6.0, 40 men, 82 women) before and one year after obesity surgery. As part of the surgery protocol, all the subjects were instructed to add sources of unsaturated fatty acids, such as rapeseed oil and fatty fish, into their diet. The results were compared with changes in serum FA composition in 122 subjects from the Finnish Diabetes Prevention study (DPS) (age 54.3±7.1 years, BMI 32.2±4.6, 28 men, 94 women).Results:The proportion of saturated FAs decreased and the proportion of n-3 and n-6 FAs increased in serum triglycerides after obesity surgery (all P<0.002). Weight loss predicted changes in quantitative amounts of saturated FAs, monounsaturated FAs, n-3 and n-6 FAs in triglycerides (P<0.002 for all). Moreover, the changes in adipose tissue FAs reflected the changes in serum FAs, and some of the changes were associated with mRNA expression of elongases and desaturases in adipose tissue (all P<0.05). In line with this the estimated activity of elongase (18:1 n-7/16:1 n-7) increased significantly after obesity surgery in all lipid fractions (all P<4 × 10−7) and the increase in the estimated activity of D5D in triglycerides was associated with higher weight loss (r=0.415, P<2 × 10−6). Changes in serum FA profile were similar after obesity surgery and lifestyle intervention, except for the change in the absolute amounts of n-3 FAs between the two studies (P=0.044).Conclusions:Beneficial changes in serum and adipose tissue FAs after obesity surgery could be associated with changes in endogenous metabolism and diet.

Fasting serum hippuric acid is elevated after bilberry (Vaccinium myrtillus) consumption and associates with improvement of fasting glucose levels and insulin secretion in persons at high risk of developing type 2 diabetes.

Urinary hippuric acid has been proposed as a biomarker for fruit, vegetable, and polyphenol consumption. We assessed how serum hippuric acid changes after a bilberry-enriched diet (BB; high anthocyanin intake) and another berry diet including strawberries, raspberries, and cloudberries (SRC; lower anthocyanin intake) and how these changes associate with insulin and glucose metabolism. Hippuric acid was measured with LC-QTOF-MS metabolite profiling analysis from fasting serum samples at baseline and after an 8-week intervention in 47 individuals with features of the metabolic syndrome who were randomized to either a BB diet (n=15), an SRC diet (n=20) or a control diet (n=12). Fasting serum hippuric acid increased significantly (3.5-fold, p=0.001) only in the BB group and correlated with changes in fasting plasma glucose concentration (r = -0.54, p<0.05) and insulin secretion (r = 0.59, p<0.05). These associations were confirmed in the Finnish Diabetes Prevention Study (n=198). Fasting serum hippuric acid is increased after consumption of anthocyanin-rich bilberries, and may contribute to the beneficial effect of bilberry consumption through its associations with better glycemic control and β-cell function.

Erratum. Gestational Diabetes Mellitus Can Be Prevented by Lifestyle Intervention: The Finnish Gestational Diabetes Prevention Study (RADIEL). A Randomized Controlled Trial. Diabetes Care 2016;39:24-30.

In the above-mentioned article, the sentence, “In addition, participants with GDM before 20 weeks of gestation were excluded from this study” was added to the end of the second paragraph in …

Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study

Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of β-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.