Aims/hypothesis
The aims of this study were to evaluate systematically the predictive power of comprehensive metabolomics profiles in predicting the future risk of type 2 diabetes, and to identify a ...panel of the most predictive metabolic markers.
Methods
We applied an unbiased systems medicine approach to mine metabolite combinations that provide added value in predicting the future incidence of type 2 diabetes beyond known risk factors. We performed mass spectrometry-based targeted, as well as global untargeted, metabolomics, measuring a total of 568 metabolites, in a Finnish cohort of 543 non-diabetic individuals from the Botnia Prospective Study, which included 146 individuals who progressed to type 2 diabetes by the end of a 10 year follow-up period. Multivariate logistic regression was used to assess statistical associations, and regularised least-squares modelling was used to perform machine learning-based risk classification and marker selection. The predictive performance of the machine learning models and marker panels was evaluated using repeated nested cross-validation, and replicated in an independent French cohort of 1044 individuals including 231 participants who progressed to type 2 diabetes during a 9 year follow-up period in the DESIR (Data from an Epidemiological Study on the Insulin Resistance Syndrome) study.
Results
Nine metabolites were negatively associated (potentially protective) and 25 were positively associated with progression to type 2 diabetes. Machine learning models based on the entire metabolome predicted progression to type 2 diabetes (area under the receiver operating characteristic curve, AUC = 0.77) significantly better than the reference model based on clinical risk factors alone (AUC = 0.68; DeLong’s
p
= 0.0009). The panel of metabolic markers selected by the machine learning-based feature selection also significantly improved the predictive performance over the reference model (AUC = 0.78;
p
= 0.00019; integrated discrimination improvement, IDI = 66.7%). This approach identified novel predictive biomarkers, such as α-tocopherol, bradykinin hydroxyproline, X-12063 and X-13435, which showed added value in predicting progression to type 2 diabetes when combined with known biomarkers such as glucose, mannose and α-hydroxybutyrate and routinely used clinical risk factors.
Conclusions/interpretation
This study provides a panel of novel metabolic markers for future efforts aimed at the prevention of type 2 diabetes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aims/hypothesis
Recent evidence suggests that oxidative stress may contribute to the pathogenesis of type 2 diabetes. The diet, and especially fruit and vegetables, contains a variety of compounds ...with antioxidant activity, which may have cumulative/synergistic antioxidant effects. The total antioxidant capacity, an index derived from dietary intake, is a single estimate of antioxidant capacity from all dietary antioxidants. The main aim of this study was to investigate the relationship between total antioxidant capacity and risk of type 2 diabetes.
Methods
Among 64,223 women (mean age 52 ± 7 years) from the French E3N-European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 1751 women had validated type 2 diabetes during 15 years of follow-up. The total antioxidant capacity was estimated with the ferric ion-reducing antioxidant power (FRAP) method. Adjusted Cox proportional hazards regression models were used to calculate HRs and 95% CIs for the associations between total antioxidant capacity and type 2 diabetes risk, adjusted for potential confounders.
Results
In multivariable models, higher levels of total antioxidant capacity were associated with a lower risk of type 2 diabetes. Compared with women in the lowest quintile, women in the third, fourth and fifth quintiles for total antioxidant capacity had HRs of 0.74 (95% CI 0.63, 0.86), 0.70 (95% CI 0.59, 0.83) and 0.73 (95% CI 0.60, 0.89), respectively. The inverse association between total antioxidant capacity and risk of type 2 diabetes was linear up to values of 15 mmol/day, after which the effect reached a plateau.
Conclusions/interpretation
Our findings suggest that the total antioxidant capacity may play an important role in reducing the risk of type 2 diabetes in middle-aged women. More studies are warranted to better understand the biological mechanisms underlying this inverse association.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aims/hypothesis
Diet is one of the main lifestyle-related factors that can modulate the inflammatory process. Surprisingly the dietary inflammatory index (DII) has been little investigated in ...relation to type 2 diabetes, and the role of BMI in this relationship is not well established. We studied this association and the role of BMI in the inflammatory process in a large population-based observational study.
Methods
A total of 70,991 women from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l’Education Nationale) cohort study were followed for 20 years. Incident type 2 diabetes cases were identified using diabetes-specific questionnaires and drug reimbursement insurance databases, and 3292 incident cases were validated. The DII was derived from a validated food frequency questionnaire. Multivariable Cox regression models estimated HRs and 95% CIs between DII and incident type 2 diabetes. Interactions were tested between DII and BMI on incident type 2 diabetes and a mediation analysis of BMI was performed.
Results
Higher DII scores, corresponding to a higher anti-inflammatory potential of the diet, were associated with a lower risk of type 2 diabetes. Compared with the 1st quintile group, women from the 2nd quintile group (HR 0.85 95% CI 0.77, 0.94) up to the 5th quintile group (HR 0.77 95% CI 0.69, 0.85) had a lower risk of type 2 diabetes before adjustment for BMI. There was an interaction between DII and BMI on type 2 diabetes risk (
p
Interaction
< 0.0001). The overall association was partly mediated by BMI (58%).
Conclusions/interpretation
Our findings suggest that a higher anti-inflammatory potential of the diet is associated with a lower risk of type 2 diabetes, and the association may be mediated by BMI. These results may improve our understanding of the mechanisms underlying the role of diet-related anti-inflammation in the pathogenesis of type 2 diabetes in women. Further studies are warranted to validate our results and evaluate whether the results are similar in men.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Despite its well-documented relation with visceral adiposity (VAT) and cardiometabolic risk (CMR), whether waist circumference (WC) should be measured in addition to body mass index (BMI) remains ...debated. This study tested the relevance of adding WC to BMI for the estimation of VAT and CMR. In the International Study of Prediction of Intra-abdominal Adiposity and Its Relationship with Cardiometabolic Risk/Intra-abdominal Adiposity, 297 physicians recruited 4,504 patients (29 countries). Both BMI and WC were measured, whereas VAT and liver fat were assessed by computed tomography. A composite CMR score was calculated. From the 4,109 patients included in the present analyses (20 ≤ BMI < 40 kg/m2 , 47% women), about 30% displayed discordant values for WC and BMI quintiles, despite a strong correlation between the 2 anthropometric variables (r = 0.87 and r = 0.84 for men and women, respectively, p <0.001). Within each single BMI unit, VAT and WC showed substantial variability between subjects (mean difference between 90th and 10th percentiles: 175 cm2 /16 cm and 137 cm2 /18 cm for VAT/WC in men and women, respectively). Within each BMI category, increasing gender-specific WC tertiles were associated with significantly higher VAT, liver fat, and with a more adverse CMR profile. In conclusion, this large international cardiometabolic study highlights the frequent discordance between BMI and WC, driven by the substantial variability in VAT for a given BMI. Within each BMI category, WC was cross-sectionally associated with VAT, liver fat, and CMR factors. Thus, WC allows a further refinement of the CMR related to any given BMI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Aims/hypothesis
The objective of this study was to evaluate the relationship of ABO blood type (A, B, AB and O), Rhesus factor (positive or negative) and a combination of the two (ABO × Rhesus) with ...type 2 diabetes mellitus risk.
Methods
In total, 82,104 women from the large prospective E3N cohort were followed between 1990 and 2008. Multivariate Cox regression models were used to estimate HRs and 95% CIs.
Results
Those with either the A (HR 1.10 95% CI 1.02, 1.18) or B (HR 1.21 95% CI 1.07, 1.36) group were at increased risk of type 2 diabetes mellitus compared with those with the O group. The association with the AB group did not reach statistical significance (HR 1.17 95% CI 0.99, 1.39). There was no difference in type 2 diabetes mellitus risk between Rhesus positive and negative groups (HR 0.96 95% CI 0.88, 1.05). When the universal donors (O
−
) were taken as the reference category, we observed an increased risk for both A
+
(HR 1.17 95% CI 1.02, 1.35) and A
−
(HR 1.22 95% CI 1.03, 1.45) individuals. The greatest increase in risk was seen for those with the B
+
blood group (HR 1.35 95% CI 1.13, 1.60). We also observed a greater type 2 diabetes mellitus risk for those with the AB
+
group (HR 1.26 95% CI 1.02, 1.57). Adjustment for fasting plasma glucose and lipid concentrations in a case–control subsample did not alter the associations.
Conclusions/interpretation
This study suggests that people with the O blood type have a lower risk of developing type 2 diabetes mellitus. Therefore, blood group should be investigated in future clinical and epidemiological studies on diabetes, and further pathophysiological research is needed to determine why individuals with blood type O have a lower risk of type 2 diabetes mellitus.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aims/hypothesis
The aim of this work was to examine whether synergistic associations with mortality exist for BMI and fasting blood glucose (FBG) and to identify FBG–BMI combined subgroups with ...higher mortality according to sex and age.
Methods
A total of 15,149,275 Korean adults participated in health examinations during 2003–2006 and were followed up until December 2018. Mortality HRs of 40 FBG–BMI combined groups were assessed by Cox proportional hazards models.
Results
During a mean 13.7 years of follow-up, 1,213,401 individuals died. A J-shaped association was seen between FBG and all-cause mortality for all BMI categories. Those with BMI <20 kg/m
2
had the highest mortality for any given FBG level, followed by those with BMI 20–22.4 kg/m
2
. The detrimental effect of elevated FBG was greater among leaner individuals than more corpulent individuals. Moreover, the synergistic adverse effects of hyperglycaemia and leanness was stronger in younger adults than in older adults. Compared with the reference group (overweight with normoglycaemia), age- and sex-adjusted HRs of the leanest with normoglycaemia (BMI <20 kg/m
2
and FBG 4.4–5.2 mmol/l), overweight with diabetes (BMI 25–27.4 kg/m
2
and FBG ≥10.0 mmol/l) and leanest with diabetes (BMI <20 kg/m
2
and FBG ≥10.0 mmol/l) were 1.29, 2.59 and 11.18, respectively, in those aged 18–44 years and 1.56, 1.72 and 2.87, respectively, in those aged 75–99 years. The identification of BMI–FBG subgroups associated with higher mortality was not straightforward, illustrated by the group with FBG 6.1–6.9 mmol/l and BMI 20–22.4 kg/m
2
having a similar or higher mortality compared with the group with FBG 7.0–9.9 mmol/l and BMI ≥22.5 kg/m
2
. In women aged <45 years with FBG <6.9 mmol/l, those with BMI ≥27.5 kg/m
2
had the highest mortality, whereas individuals with BMI <20 kg/m
2
had the highest mortality for each given FBG level in other age and sex groups.
Conclusions/interpretation
Leanness and hyperglycaemia interact together to increase mortality in a supra-multiplicative manner, especially in younger adults; the interactions of BMI, FBG, sex and age with mortality are complex.
Graphical abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Purpose
To evaluate three partial nephrectomies (PN) procedures: open (OPN), standard laparoscopy (LPN), and robot-assisted laparoscopy (RAPN), for the risk of initial complications and ...rehospitalization for two years after the surgery.
Materials and methods
From the French national hospital database (PMSI-MCO), every hospitalization in French hospitals for renal tumor PN in 2016–2017 were extracted. Complications were documented from the initial hospitalization and any rehospitalization over two years. Chi-square and ANOVA tests compared the frequency of complications and length of initial hospitalization between the three surgical procedures. Relative risks (RR) and 95% confidence intervals were computed.
Results
The 9119 initial hospitalizations included 4035 OPN, 1709 LPN, and 1900 RAPN; 1475 were excluded as the laparoscopic procedure performed was not determined. The average length of hospitalization was 8.1, 6.2, and 4.5 days for OPN, LPN, and RAPN, respectively. Compared to OPN, there were fewer complications at the time of initial hospitalization for the mini-invasive procedures: 29% for OPN vs. 20% for LPN (0.70 0.63;0.78) and 12% for RAPN (RR=0.43, 95%CI 0.38;0.49). For RAPN compared to LPN, there were fewer haemorrhages (RR=0.55 0.43;0.72), anemia (0.69 {0.48;0.98), and sepsis (0.51 0.36;0.71); during follow up, there were fewer urinary tract infections (0.64 0.45;0.91) but more infectious lung diseases (1.69 1.03;2.76). Over the two-year postoperative period, RAPN was associated with fewer acute renal failures (RR=0.73 0.55;0.98), renal abscesses (0.41 0.23;0.74), parietal complications (0.69 0.52;0.92) and urinary tract infections (0.54 0.40;0.73) than for OPN.
Conclusions
Conservative renal surgery is associated with postoperative morbidity related to the surgical procedure fashion. Mini-invasive procedures, especially robot-assisted surgery, had fewer complications and shorter hospital lengths of stay
Purpose
In France, transurethral resection of the prostate (TURP) is still the most commonly used surgical treatment for medium sized benign prostatic hyperplasia (BPH), but the Holmium Laser ...Enucleation of the Prostate (HoLEP) and laser vaporization procedures are becoming more common. For these three surgical procedures, we evaluate the initial complications, the short term (3 months) and the 4–12-month postoperative complications necessitating re-hospitalization.
Methods
From the French national hospital data base (PMSI-MCO), all hospitalizations for BPH treatment in 2018 were extracted. We document the complications during the initial hospitalization and any subsequent rehospitalizations during the one-year postoperative period.
Results
In 2018, 67,220 patients were treated for BPH: 46,242 TURP, 13,509 HoLEP and 7469 laser vaporization. Age and anticoagulation medications were similar for men treated by the three procedures, but TURP patients were more often hypertensive. Infections and hemorrhagic complications were the most common complications at the initial hospitalization: 17%, 10%, 13% for infections and 15%, 8.1%, 11% for hemorrhagic complications respectively, and TURP performed worse than the other two procedures at the initial hospitalization. During the first three months and then the subsequent nine months, there were fewer complications than initially, with little difference between the three procedures, all differences being less than 1%.
Conclusion
Laser vaporization techniques led to fewer complications. However, the PMSI-MCO only registers complications during hospitalizations. This study should be extended to non-hospitalized, more minor complications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We recently described a human blood microbiome and a connection between this microbiome and the onset of diabetes. The aim of the current study was to assess the association between blood microbiota ...and incident cardiovascular disease.
D.E.S.I.R. is a longitudinal study with the primary aim of describing the natural history of the metabolic syndrome and its complications. Participants were evaluated at inclusion and at 3-, 6-, and 9-yearly follow-up visits. The 16S ribosomal DNA bacterial gene sequence, that is common to the vast majority of bacteria (Eubac) and a sequence that mostly represents Proteobacteria (Pbac), were measured in blood collected at baseline from 3936 participants. 73 incident cases of acute cardiovascular events, including 30 myocardial infarctions were recorded. Eubac was positively correlated with Pbac (r = 0.59; P<0.0001). In those destined to have cardiovascular complications, Eubac was lower (0.14±0.26 vs 0.12±0.29 ng/µl; P = 0.02) whereas a non significant increase in Pbac was observed. In multivariate Cox analysis, Eubac was inversely correlated with the onset of cardiovascular complications, (hazards ratio 0.50 95% CI 0.35-0.70) whereas Pbac (1.56, 95%CI 1.12-2.15) was directly correlated.
Pbac and Eubac were shown to be independent markers of the risk of cardiovascular disease. This finding is evidence for the new concept of the role played by blood microbiota dysbiosis on atherothrombotic disease. This concept may help to elucidate the relation between bacteria and cardiovascular disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE: Water intake alters vasopressin secretion. Recent findings reveal an independent association between plasma copeptin, a surrogate for vasopressin, and risk of diabetes. RESEARCH DESIGN AND ...METHODS: Participants were 3,615 middle-aged men and women, with normal baseline fasting glycemia (FG), who were recruited in a 9-year follow-up study. Odds ratios (ORs) and 95% CIs for the incidence of hyperglycemia (FG ≥6.1 mmol/L or treatment for diabetes) were calculated according to daily water intake classes based on a self-administered questionnaire. RESULTS: During follow-up, there were 565 incident cases of hyperglycemia. After adjustment for confounding factors, ORs (95% CIs) for hyperglycemia associated with classes of water intake (<0.5 L, n = 677; 0.5 to <1.0 L, n = 1,754; and >1.0 L, n = 1,184) were 1.00, 0.68 (0.52–0.89), and 0.79 (0.59–1.05), respectively (P = 0.016). CONCLUSIONS: Self-reported water intake was inversely and independently associated with the risk of developing hyperglycemia.
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