Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General Population
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ABSTRACT:
SUBMITTER: Sokooti S
PROVIDER: S-EPMC9323856 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background Type 2 diabetes is increasing worldwide. Traditionally, only hypertriglyceridemia is considered a risk factor. We investigated whether also normal triglycerides prospectively associate with incident type 2 diabetes in healthy subjects. Methods Incident type 2 diabetes was determined in healthy individuals with normal triglyceride levels from a prospective longitudinal cohort study (PREVEND, n = 2085, 11.4-year median follow-up). Results Type 2 diabetes incidence was 3.8%. In linear regression analysis baseline insulin, HOMA-IR, total cholesterol, HDL cholesterol, eGFR, systolic blood pressure (all p < 0.001), glucose, age and creatinine (all p < 0.01) independently associated with triglycerides within the normal range, comparable to what would be expected from associations with increased triglycerides. In Kaplan-Meier analysis sex-stratified tertiles of normal triglycerides prospectively associated with de novo type 2 diabetes (p < 0.001). Cox regression confirmed a significant prospective association independent of HOMA-IR [HR (95% CI), 1.39 (1.12, 1.74), p = 0.002] and several other recognized risk factors. Conclusions Even in healthy subjects without metabolic syndrome increasing triglyceride levels within the normal range confer a continuous increase in type 2 diabetes incidence. These data indicate that virtually everyone could potentially benefit from triglyceride lowering, further encouraging implementation of lifestyle changes in the general population. Supplementary information The online version contains supplementary material available at 10.1186/s12933-022-01530-8.
| S-EPMC9206357 | biostudies-literature
Project description:Aims/hypothesisEarlier studies have shown that skin autofluorescence measured with an AGE reader estimates the accumulation of AGEs in the skin, which increases with ageing and is associated with the metabolic syndrome and type 2 diabetes. In the present study, we examined whether the measurement of skin autofluorescence can predict 4 year risk of incident type 2 diabetes, cardiovascular disease (CVD) and mortality in the general population.MethodsFor this prospective analysis, we included 72,880 participants of the Dutch Lifelines Cohort Study, who underwent baseline investigations between 2007 and 2013, had validated baseline skin autofluorescence values available and were not known to have diabetes or CVD. Individuals were diagnosed with incident type 2 diabetes by self-report or by a fasting blood glucose ≥7.0 mmol/l or HbA1c ≥48 mmol/mol (≥6.5%) at follow-up. Participants were diagnosed as having incident CVD (myocardial infarction, coronary interventions, cerebrovascular accident, transient ischaemic attack, intermittent claudication or vascular surgery) by self-report. Mortality was ascertained using the Municipal Personal Records Database.ResultsAfter a median follow-up of 4 years (range 0.5-10 years), 1056 participants (1.4%) had developed type 2 diabetes, 1258 individuals (1.7%) were diagnosed with CVD, while 928 (1.3%) had died. Baseline skin autofluorescence was elevated in participants with incident type 2 diabetes and/or CVD and in those who had died (all p < 0.001), compared with individuals who survived and remained free of the two diseases. Skin autofluorescence predicted the development of type 2 diabetes, CVD and mortality, independent of several traditional risk factors, such as the metabolic syndrome, glucose and HbA1c.Conclusions/interpretationThe non-invasive skin autofluorescence measurement is of clinical value for screening for future risk of type 2 diabetes, CVD and mortality, independent of glycaemic measures and the metabolic syndrome.
| S-EPMC6323092 | biostudies-literature
Project description:While it is established that psychosocial stress increases the risk of developing diabetes mellitus (DM), two key knowledge gaps remain: 1) the neurobiological mechanisms that are involved in mediating that risk, and 2) the role, if any, that adiposity plays in that mechanism. We tested the hypotheses that: 1) metabolic activity in the amygdala (AmygA), a key center involved in the neurobiological response to stress, associates with subsequent DM risk, and 2) this association is independent of adiposity. AmygA and adipose tissue volumes were measured, and serial blood assessments for DM were obtained in 232 subjects who underwent combined 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) imaging. Higher baseline AmygA predicted subsequent, new-onset DM, independently of adiposity and other DM risk factors. Furthermore, higher adiposity only increased DM risk in the presence of higher AmygA. In a separate cross-sectional cohort, higher AmygA associated with higher insulin resistance. Accordingly, the current study shows, for the first time, that activity in a stress-responsive neural region predicts the onset of DM. Further, we observed that this neurobiological activity acts independently of, but also synergistically with adiposity to increase DM risk. These findings suggest novel therapeutic targets to help manage and possibly prevent DM.
| S-EPMC6398601 | biostudies-literature
Project description:BackgroundEarly detection and risk factor control prevent chronic kidney disease (CKD) progression. Evaluation of peripheral autonomic dysfunction may detect incident cardiovascular-renal events in type 2 diabetes (T2D).MethodsSUDOSCAN, a non-invasive tool, provides an age-adjusted electrochemical skin conductance (ESC) composite score incorporating hands/feet ESC measurements, with a score ≤53 indicating sudomotor dysfunction. A consecutive cohort of 2833 Chinese adults underwent structured diabetes assessment in 2012-13; 2028 participants without preexisting cardiovascular disease (CVD) and CKD were monitored for incident cardiovascular-renal events until 2015.ResultsIn this prospective cohort {mean age 57.0 [standard deviation (SD) 10.0] years; median T2D duration 7.0 [interquartile range (IQR) 3.0-13.0] years; 56.1% men; 72.5% never-smokers; baseline ESC composite score 60.7 (SD 14.5)}, 163 (8.0%) and 25 (1.2%) participants developed incident CKD and CVD, respectively, after 2.3 years of follow-up. The adjusted hazard ratios (aHRs) per 1-unit decrease in the ESC composite score for incident CKD, CVD and all-cause death were 1.02 [95% confidence interval (CI) 1.01-1.04], 1.04 (1.00-1.07) and 1.04 (1.00-1.08), respectively. Compared with participants with an ESC composite score >53, those with a score ≤53 had an aHR of 1.56 (95% CI 1.09-2.23) for CKD and 3.11 (95% CI 1.27-7.62) for CVD, independent of common risk markers. When added to clinical variables (sex and duration of diabetes), the ESC composite score improved discrimination of all outcomes with appropriate reclassification of CKD risk.ConclusionsA low ESC composite score independently predicts incident cardiovascular-renal events and death in T2D, which may improve the screening strategy for early intervention.
| S-EPMC6680097 | biostudies-literature
Project description:BackgroundType 2 diabetes is associated with both impaired insulin action at target tissues and impaired insulin secretion in pancreatic beta cells. Mitochondrial dysfunction may play a role in both insulin resistance and impaired insulin secretion. Plasma creatine has been proposed as a potential marker for mitochondrial dysfunction. We aimed to investigate the association between plasma creatine and incident type 2 diabetes.MethodsWe measured fasting plasma creatine concentrations by nuclear magnetic resonance spectroscopy in participants of the general population-based PREVEND study. The study outcome was incident type 2 diabetes, defined as a fasting plasma glucose ≥7.0 mmol/L (126 mg/dl); a random sample plasma glucose ≥11.1 mmol/L (200 mg/dl); self-report of a physician diagnosis or the use of glucose-lowering medications based on a central pharmacy registration. Associations of plasma creatine with type 2 diabetes were quantified using Cox proportional hazards models and were adjusted for potential confounders.ResultsWe included 4735 participants aged 52 ± 11 years, of whom 49% were male. Mean plasma creatine concentrations were 36.7 ± 17.6 µmol/L, with lower concentrations in males than in females (30.4 ± 15.1 µmol/L vs. 42.7 ± 17.7 µmol/L; p for difference <.001). During 7.3 [6.2-7.7] years of follow-up, 235 (5.4%) participants developed type 2 diabetes. Higher plasma creatine concentrations were associated with an increased risk of incident type 2 diabetes (HR per SD change: 1.27 [95% CI: 1.11-1.44]; p < .001), independent of potential confounders. This association was strongly modified by sex (p interaction <.001). Higher plasma creatine was associated with an increased risk of incident type 2 diabetes in males (HR: 1.40 [1.17-1.67]; p < .001), but not in females (HR: 1.10 [0.90-1.34]; p = .37).ConclusionFasting plasma creatine concentrations are lower in males than in females. Higher plasma creatine is associated with an increased risk of type 2 diabetes in males.
| S-EPMC8048485 | biostudies-literature
Project description:OBJECTIVE:We tested whether an elevation in the serum proinsulin-to-C-peptide ratio (PI:C), a biomarker of ?-cell endoplasmic reticulum (ER) dysfunction, was associated with progression to type 1 diabetes. RESEARCH DESIGN AND METHODS:Fasting total PI and C levels were measured in banked serum samples obtained from TrialNet Pathway to Prevention (PTP) participants, a cohort of autoantibody-positive relatives without diabetes of individuals with type 1 diabetes. Samples were obtained ?12 months before diabetes onset from PTP progressors in whom diabetes developed (n = 60), and were compared with age-, sex-, and BMI-matched nonprogressors who remained normoglycemic (n = 58). PI:C ratios were calculated as molar ratios and were multiplied by 100% to obtain PI levels as a percentage of C levels. RESULTS:Although absolute PI levels did not differ between groups, PI:C ratios were significantly increased in antibody-positive subjects in whom there was progression to diabetes compared with nonprogressors (median 1.81% vs. 1.17%, P = 0.03). The difference between groups was most pronounced in subjects who were ?10 years old, where the median progressor PI:C ratio was nearly triple that of nonprogressors; 90.0% of subjects in this age group within the upper PI:C quartile progressed to the development of diabetes. Logistic regression analysis, adjusted for age and BMI, demonstrated increased odds of progression for higher natural log PI:C ratio values (odds ratio 1.44, 95% CI 1.02, 2.05). CONCLUSIONS:These data suggest that ?-cell ER dysfunction precedes type 1 diabetes onset, especially in younger children. Elevations in the serum PI:C ratio may have utility in predicting the onset of type 1 diabetes in the presymptomatic phase.
| S-EPMC5001142 | biostudies-literature
Project description:Background and Purpose- Fatigue is a common symptom among stroke survivors and in general practice. However, the clinical significance of fatigue and its relationship to incident stroke is unclear. The aim of this study was to examine the relationship between self-reported fatigue and the incidence of stroke in a general population. Methods- This was a prospective, population-based study. The study population was 15 654 men and women aged 39 to 79 years recruited in 1993 to 1997 and followed till March 2016. Fatigue was assessed at 18 months after baseline using the vitality domain of the Short Form 36 questionnaire. Cox proportional hazard models were constructed to describe the prospective relationship between baseline fatigue and incident stroke adjusting for age, sex, systolic blood pressure, cholesterol, physical activity, smoking status, alcohol consumption, fruit and vegetable consumption, diabetes mellitus, body mass index, vitamin supplement use, education level, Townsend deprivation index, and occupational social class. Incident stroke was ascertained using death certificates and hospital record linkage data. Results- Through 249 248 person-years of follow-up, 1509 incident strokes occurred. Participants who reported the highest level of fatigue (quartile 4) were more likely to be women, to be multimorbid, and to perceive their health as fair or poor. We observed ≈50% relative risk increase in stroke risk (hazard ratio, 1.49 [95% CI, 1.29-1.71]) in those who reported the highest level of fatigue compared with those who reported the lowest level of fatigue (Q4 versus Q1). This relationship remained unaltered regardless of anemia status, the presence or absence of chronic bronchitis, thyroid dysfunction, or depression. Conclusions- Self-report fatigue assessed by the vitality domain of the Short Form 36 questionnaire predicts the risk of future stroke at the general population level. Identifying and addressing stroke risk factors in those who report fatigue in general practice may have substantial benefit at the population level.
| S-EPMC7611120 | biostudies-literature
Project description:BackgroundSubtle impairments in left ventricular (LV) function and geometry are common findings in individuals with diabetes. However, whether these impairments precede the development of diabetes mellitus (DM) is not entirely clear.MethodsEchocardiograms from 1710 individuals from the general population free of prevalent diabetes mellitus were analyzed. Left ventricular (LV) concentric geometry was defined as either LV concentric remodeling or LV concentric hypertrophy as directed in contemporary guidelines. The severity of LV concentricity was assessed by relative wall thickness (RWT) calculated as posterior wall thickness (PWT) indexed to left ventricular internal diameter at end diastole (LVIDd) (RWT = 2 * PWT/LVIDd). End-point was incident DM.ResultsMedian follow-up time was 12.6 years (IQR: 12.0-12.8 years). Follow-up was a 100%. A total of 55 participants (3.3%) developed DM during follow-up. At baseline, the prevalence of a concentric LV geometric pattern was significantly higher (41.8% vs 20.3%, p < 0.001) in individuals who developed DM during follow-up. In a final multivariable model adjusting for established DM risk factors including HbA1c, BMI and plasma glucose, LV concentric geometry and RWT remained significantly associated with incident DM (LV concentric geometry: HR 1.99, 95% CI 1.11-3.57, p = 0.021) (RWT: HR 1.41, 95% CI 1.06-1.86, p = 0.017, per 0.1 increase). This association remained despite adjustment for established risk factors for DM.ConclusionAltered LV geometry may precede the development of DM. LV concentric geometry determined by echocardiography and the severity of LV concentricity evaluated as RWT are associated with incident DM in the general population.
| S-EPMC6427881 | biostudies-literature
Project description:We developed two novel sperm epigenetic clocks by applying Super Learner, an ensemble machine learning algorithm, to predict age from sperm EPIC array DNA methylation data via individual CpG sites and differentially methylated regions (DMRs). Overall, our cox model showed that one-year increase in our developed sperm epigenetic age (SEA) was associated with up to 15% reduction in couples time-to-pregnancy (TTP).
2022-07-06 | GSE185445 | GEO
Project description:OBJECTIVE:Most previous studies on cardiovascular health (CVH) and incident type 2 diabetes (T2D) have used a single measure of CVH, and none have investigated the association with impaired fasting glucose (IFG). We examined the association between changes in CVH and incident T2D and IFG. RESEARCH DESIGN AND METHODS:Within the Whitehall II study, CVH was examined every 5 years from 1991/93 until 2015/16. Subjects with 0-2, 3-4, and 5-6 ideal metrics of CVH from the American Heart Association were categorized as having low, moderate, or high CVH, respectively. RESULTS:There were 6,234 participants (mean age 49.8 ± 6.0 years, 70% male) without prior cardiovascular disease and T2D, including 5,015 who were additionally free from IFG at baseline. Over a median follow-up of 24.8 (interquartile range 24.0-25.2) years, 895 and 1,703 incident cases of T2D and IFG occurred, respectively. Change in CVH between 1991/93 and 2002/04 was calculated among 4,464 participants free from CVD and T2D and among 2,795 participants additionally free from IFG. In multivariate analysis, compared with those with stable low CVH, risk of T2D was lower in those with initially high CVH (hazard ratio [HR] 0.21; 95% CI 0.09, 0.51), those who had persistently moderate CVH or changed from moderate to high CVH (moderate-moderate/high; HR 0.53; 95% CI 0.41, 0.69), low-moderate/high (HR 0.62; 95% CI 0.45, 0.86), and moderate-low (HR 0.74; 95% CI 0.56, 0.98). Results were similar for IFG, but the effect sizes were smaller. CONCLUSIONS:Compared with stable low CVH, other patterns of change in CVH were associated with lower risk of T2D and IFG.
| S-EPMC7364667 | biostudies-literature