Mette Lundgren Nielsen

Enhanced predictive capability of a 1-hour oral glucose tolerance test : A prospective population-based cohort study

OBJECTIVE To examine whether the 1-h blood glucose measurement would be a more suitable screening tool for assessing the risk of diabetes and its complications than the 2-h measurement. RESEARCH DESIGN AND METHODS We conducted a prospective population-based cohort study of 4,867 men, randomly selected from prespecified birth cohorts between 1921 and 1949, who underwent an oral glucose tolerance test with blood glucose measurements at 0, 1, and 2 h. Subjects were followed for up to 39 years, with registry-based recording of events. Discriminative abilities of elevated 1-h (≥8.6 mmol/L) versus 2-h (≥7.8 mmol/L) glucose for predicting incident type 2 diabetes, vascular complications, and mortality were compared using Kaplan-Meier analysis, Cox proportional hazards regression, and net reclassification improvement. RESULTS Median age was 48 years (interquartile range [IQR] 48–49). During follow-up (median 33 years [IQR 24–37]), 636 (13%) developed type 2 diabetes. Elevated 1-h glucose was associated with incident diabetes (hazard ratio 3.40 [95% CI 2.90–3.98], P < 0.001) and provided better risk assessment than impaired glucose tolerance (Harrell concordance index 0.637 vs. 0.511, P < 0.001). Addition of a 1-h measurement in subjects stratified by fasting glucose provided greater net reclassification improvement than the addition of a 2-h measurement (0.214 vs. 0.016, respectively). Finally, the 1-h glucose was significantly associated with vascular complications and mortality. CONCLUSIONS The 1-h blood glucose level is a stronger predictor of future type 2 diabetes than the 2-h level and is associated with diabetes complications and mortality.

Follow-up duration influences the relative importance of OGTT and optimal timing of glucose measurements for predicting future type 2 diabetes

OBJECTIVE To examine the impact of follow-up duration on the incremental prognostic yield of a baseline oral glucose tolerance test (OGTT) for predicting type 2 diabetes and to assess the discrimination ability of blood glucose (BG) obtained at different time points during OGTT. DESIGN A prospective, population-based cohort study (Malmö Preventive Project) with inclusion of subjects from 1974 to 1992. METHODS A total of 5256 men without diabetes, who had BG measured at 0, 20, 40, 60, 90, and 120 min during OGTT (30 g/m2 glucose), were followed for 30 years. Incident type 2 diabetes was recorded using registries. The performance of OGTT added to a clinical prediction model (age, body mass index (BMI), diastolic blood pressure, fasting BG, triglycerides, and family history of diabetes) was assessed using Harrells concordance index (C-index) and integrated discrimination improvement (IDI). RESULTS Median age was 48 years, mean BMI 24.9 kg/m2, and mean fasting BG 4.7 mmol/L. Models with added post-load BG performed better than the clinical model (C-index: P = 0.08 for BG at 120 min at 5 years, otherwise P ≤ 0.045; IDI: P ≥ 0.06 for BG at 60 and 90 min at 5 years, otherwise P ≤ 0.01). With a longer follow-up duration, C-index decreased, and the C-index increase associated with OGTT was attenuated. Models including BG at 60 or 90 min performed significantly better than the model with BG at 120 min, evident beyond follow-up of 10 and 5 years, respectively. CONCLUSIONS OGTT provided incremental prognostic yield for type 2 diabetes prediction. BG measured at 60 or 90 min provided better discrimination than BG at 120 min.

Worsening diastolic function is associated with elevated fasting plasma glucose and increased left ventricular mass in a supra-additive fashion in an elderly, healthy, Swedish population

AIMS To examine whether increasing fasting plasma glucose (FPG) levels were associated with worsening left ventricular (LV) diastolic function, independently of LV mass index (LVMI) in elderly, otherwise healthy subjects. METHODS AND RESULTS We tested cross-sectional associations between echocardiographically determined averaged E/é ratio/diastolic function, LVMI, cardiovascular risk factors, and FPG categorized as normal (NFG), impaired (IFG), and new-onset diabetes mellitus (DM), in 483 men and 208 women aged 56-79 years without overt cardiovascular disease, who received no cardiovascular, anti-diabetic, or lipid-lowering drugs and had a preserved LV ejection fraction >50%. Median E/é was significantly higher among subjects with diabetes than those without (8 vs. 7; p = 0.03), as was the prevalence of grade 2 or 3 diastolic dysfunction (25% vs. 16%; p = 0.02). E/é and diastolic function were significantly associated with LVMI (p ≤ 0.002), but not FPG category, on multivariable analysis. However, interaction analyses revealed that increasing LVMI was primarily associated with worsening diastolic function (higher E/é) in subjects with FPG > 6 mmol/L (β=0.005 for IFG and DM vs. 0.001 for NFG; p = 0.02), whereas increasing systolic blood pressure was primarily associated with worsening diastolic function (higher E/é) in subjects with FPG ≤ 6.9 mmol/L (β = 0.005 for NFG and 0.003 for IFG vs. -0.001 for DM; p=0.001). CONCLUSION Diastolic dysfunction was significantly more prevalent among patients with DM than those without. The importance of LVMI increased, but the importance of systolic blood pressure decreased with higher FPG category.

Uncontrolled hypertension is associated with coronary artery calcification and electrocardiographic left ventricular hypertrophy: a case-control study.

We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population, and evaluate the association between CAC and LVH in patients with uncontrolled hypertension. Cases were patients with uncontrolled hypertension, whereas the controls were random individuals from the general population without cardiovascular disease. CAC score was assessed using a non-contrast computed tomographic scan. LVH was evaluated using the Sokolow–Lyon voltage combination and Cornell voltage-duration product, respectively. Associations between CAC, LVH and traditional cardiovascular risk factors were tested by means of ordinal, conditional and classic binary logistic regression models. We found that uncontrolled hypertension was independently associated with both an ordinal CAC score category (odds ratio (OR) 3.9 (95% CI, 1.6–9.1), P=0.002), the presence of CAC score>99 (OR 4.5 (95% CI, 1.4–14.7), P=0.01) and electrocardiographic LVH (OR 10.1 (95% CI, 3.4–30.2), P<0.001) on both univariate and multivariable analyses. There was, however, no correlation between CAC and LVH. The lack of an association between CAC and LVH suggests that they are markers of different complications of hypertension and may have independent predictive values. Patients with both CAC and LVH may be at higher risk than those in whom only one of these markers is present.

Factors associated with diagnostic discrepancy for left ventricular hypertrophy between electrocardiography and echocardiography

Abstract Objective: To investigate the influence of cardiovascular risk factors, including fasting plasma glucose (FPG), on the association between electrocardiographic (ECG) and echocardiographic left ventricular hypertrophy (LVH) in an elderly population. Methods: We tested cross-sectional associations between electrocardiographic and echocardiographic LVH, defining LVH according to the Sokolow-Lyon voltage combination, Cornell voltage-duration product, or left ventricular mass index (LVMI). Differences between standardized LVMI and Sokolow-Lyon voltage combination or Cornell voltage-duration product (absolute value/cut-off value for LVH) were used as outcome variables in order to identify explanatory variables associated with diagnostic discrepancies between ECG and echocardiography. Results: Of the 1382 subjects included, 77% did not display any signs of LVH, 6% had LVH defined by ECG only, 13% had LVH defined by echocardiography only, and 5% had LVH on both ECG and echocardiography. Older subjects and those with higher blood pressure and RWT were more likely to have a relatively greater LVMI on echocardiography than that predicted on ECG (odds ratio: 1.65 per 10 years (95% confidence interval (CI): 1.27-2.15), p = .0002, odds ratio: 1.17 per 10 mmHg (95% CI: 1.09-1.25), p < .0001, and odds ratio: 1.21 per 0.10 (95% CI: 1.02-1.42), p = .03). In addition, discrepancy was also seen in females and subjects receiving antihypertensive medication (odds ratio: 1.41 (95% CI: 1.04-1.89), p = .03 and odds ratio: 1.41 (95% CI: 1.06-1.87), p = .02), but FPG did not independently influence discrepancy between ECG and echocardiography. Conclusion: Age, blood pressure, female sex, greater RWT and use of antihypertensive medication were associated with a greater risk of non-consistency between LVH determined by ECG and echocardiography.

4B.07: BASELINE CARDIAC TROPONIN T LEVELS ARE ELEVATED IN SUBJECTS WITH UNTREATED DIABETES MELLITUS: A CROSS-SECTIONAL STUDY.

Objective: Cardiac troponins are biomarkers of myocardial injury and serve both diagnostic and prognostic purposes. Even mild elevations represent subclinical myocardial damage in the general population. The objective of this study was to investigate the relationship between glucometabolic status and cardiac troponin T in middle-aged or older apparently healthy subjects. Design and method: We examined cross-sectional associations between high-sensitivity cardiac troponin T (hsTnT) and FPG categorized as normal fasting glucose (NFG: FPG</=6.0mmol/L), impaired fasting glucose (IFG: FPG 6.1–6.9mmol/L), and diabetes mellitus (DM: FPG>/=7.0mmol/L), in 535 men and 226 women aged 56–79 years without overt cardiovascular disease who received no cardiovascular, antidiabetic or lipid lowering drugs, using multiple linear regression analysis. Results: FPG category (r = 0.159; p < 0.001) was positively correlated with hsTnT. Mean hsTnT levels increased significantly with worsening glucometabolic status (NFG: 7.55 ng/L +/- standard deviation 3.99 ng/L; IFG: 8.09 ng/L +/- 6.81 ng/L; DM: 10.28 ng/L +/- 7.55 ng/L; p < 0.001). Levels were significantly higher in subjects with DM compared to NFG (p < 0.001) and IFG (p = 0.005), but there was no significant difference between subjects with NFG and IFG (p = 0.26). After adjusting for age and sex, FPG category remained significantly predictive of hsTnT (B = 1.08 [95% confidence interval (CI), 0.56–1.59]; p < 0.001). After further adjusting for traditional cardiovascular risk factors, cystatin C levels, and electrocardiographic left ventricular hypertrophy (LVH) defined by the Sokolow-Lyon index and/or Cornell voltage-duration product, FPG category remained significantly associated with hsTnT (B = 0.87 [95% CI, 0.35–1.39]; p = 0.001), independently of age (B = 0.29 [95% CI, 0.22–0.36]; p < 0.001), sex (B = 2.08 [95% CI, 1.20–2.95]; p < 0.001), systolic blood pressure (B = 0.032 [95% CI, 0.012–0.051]; p = 0.001), and cystatin C (B = 3.69 [95% CI, 1.60–5.79]; p = 0.001). There was a significant interaction between FPG category and age (NFG: B = 0.22 [95% CI, 0.16–0.29]; IFG: B = 0.33 [95% CI, 0.18–0.48]; DM: B = 0.41 [95% CI, 0.20–0.62]; p = 0.03). Conclusions: In middle-aged or older apparently healthy subjects, untreated DM was associated with higher levels of hsTnT, independently of traditional cardiovascular risk factors. The importance of age increased with worsening glucometabolic status.

One-hour glucose value as a long-term predictor of cardiovascular morbidity and mortality: the Malmö Preventive Project

OBJECTIVE To examine the predictive capability of a 1-h vs 2-h postload glucose value for cardiovascular morbidity and mortality. DESIGN Prospective, population-based cohort study (Malmö Preventive Project) with subject inclusion 1974-1992. METHODS 4934 men without known diabetes and cardiovascular disease, who had blood glucose (BG) measured at 0, 20, 40, 60, 90 and 120 min during an OGTT (30 g glucose per m2 body surface area), were followed for 27 years. Data on cardiovascular events and death were obtained through national and local registries. Predictive capabilities of fasting BG (FBG) and glucose values obtained during OGTT alone and added to a clinical prediction model comprising traditional cardiovascular risk factors were assessed using Harrells concordance index (C-index) and integrated discrimination improvement (IDI). RESULTS Median age was 48 (25th-75th percentile: 48-49) years and mean FBG 4.6 ± 0.6 mmol/L. FBG and 2-h postload BG did not independently predict cardiovascular events or death. Conversely, 1-h postload BG predicted cardiovascular morbidity and mortality and remained an independent predictor of cardiovascular death (HR: 1.09, 95% CI: 1.01-1.17, P = 0.02) and all-cause mortality (HR: 1.10, 95% CI: 1.05-1.16, P < 0.0001) after adjusting for various traditional risk factors. Clinical risk factors with added 1-h postload BG performed better than clinical risk factors alone, in predicting cardiovascular death (likelihood-ratio test, P = 0.02) and all-cause mortality (likelihood-ratio test, P = 0.0001; significant IDI, P = 0.0003). CONCLUSION Among men without known diabetes, addition of 1-h BG, but not FBG or 2-h BG, to clinical risk factors provided incremental prognostic yield for prediction of cardiovascular death and all-cause mortality.

Impact of fasting glucose on electrocardiographic left ventricular hypertrophy in an elderly general population

Abstract Objective. To evaluate relationships between fasting plasma glucose (FPG), other cardiovascular risk markers and left ventricular hypertrophy (LVH) as detected by electrocardiography. Methods. Subjects were selected randomly from groups defined by FPG. Traditional risk markers were assessed. LVH was defined by either Cornell voltage–duration product (CP) or Sokolow–Lyon voltage combination (SL), and univariate and multivariable regressions were performed in search of explanatory factors for the presence of LVH and the values of CP and SL. Results. Of the 1759 subjects included, 1007 had a history of cardiovascular disease and/or medical treatment, while 752 subjects appeared to be healthy. We found an independent association between FPG and LVH (odds ratio 1.152, p = 0.042] as well as continuous CP (beta = 0.126, p = 0.007) in healthy men. As expected, we found an association between systolic blood pressure and LVH (odds ratio 1.020, p < 0.001) among healthy subjects, but only in subjects with FPG < 6 mmol/l (p = 0.04 for interaction). Conclusions. We found an independent association between FPG and LVH in healthy men, and no potentiating effect by FPG on the impact of hypertension.

OS 27-06 INDEPENDENT PROGNOSTIC VALUE OF LEFT VENTRICULAR MASS, DIASTOLIC FUNCTION, AND FASTING PLASMA GLUCOSE: A POPULATION-BASED COHORT STUDY.

Objective: To explore the independent prognostic value of left ventricular (LV) mass, diastolic function, and fasting plasma glucose (FPG) for the prediction of incident cardiac events in a random population sample. Design and Method: 415 women and 999 men aged 56–79 years, included between 2002-2006, underwent echocardiography based on groups defined by FPG, i.e. normal (NFG): FPG ⩽ 6.0 mmol/L; impaired (IFG): FPG 6.1–6.9 mmol/L; and diabetes mellitus (DM): FPG ≥ 7.0 mmol/L, self-reported DM, and/or on anti-diabetic drugs. Additive prognostic value of FPG category and echocardiography (LV mass index (LVMI), LV hypertrophy (LVH), averaged E/é, and diastolic function graded as normal, grade 1, or grade 2 + 3 diastolic dysfunction) to a prediction model with traditional cardiovascular (CV) risk factors was assessed using Cox proportional hazards regression. Cardiac events were defined as myocardial infarction, coronary revascularization, or heart failure. Results: 37 % were classified as NFG, 26 % as IFG, and 37 % as DM. Median LVMI and E/é were 86 [74–102] g/m2 and 8 [6–10], respectively. Over a median follow-up time of 7.8 [7.2–8.7] years, 181 events occurred. The simple prediction model included age, gender, systolic blood pressure, heart rate, previous CV disease, and use of CV medication. Addition of averaged E/é (likelihood-ratio c2 11.69, p < 0.001) or LVMI (likelihood-ratio c2 4.52, p = 0.03) significantly improved the model, whereas FPG category did not (likelihood-ratio c2 0.48, p = 0.79). Furthermore, we detected significant interactions between both FPG category and LVH (likelihood-ratio c2 9.93, p = 0.007) and FPG category and diastolic function (likelihood-ratio c2 11.65, p = 0.02) for prediction of cardiac events. Conclusions: LVMI and E/é, but not FPG category provided additional adverse prognostic value on top of traditional CV risk factors. The combination of both glucometabolic and echocardiographic abnormalities was associated with a progressively greater risk of cardiac events.

Hemodynamic and metabolic factors in the prediction of diastolic dysfunction

Objective: To explore possible hemodynamic and metabolic determinants of diastolic dysfunction in a random population sample. Design and method: We examined associations between hemodynamic factors (systolic blood pressure (SBP), heart rate (HR)), metabolic factors (fasting insulin, fasting plasma glucose, 2-hour glucose during oral glucose tolerance test (OGTT), oral disposition index (DIo), and Homeostatic Model Assessment (HOMA) derived indices of beta-cell function (HOMA-2B), insulin sensitivity (HOMA-2S), and insulin resistance (HOMA-2IR)), other traditional cardiovascular risk factors, and later detection of grade 2 or 3 diastolic dysfunction (DD) in 243 men and 22 women aged 28 to 57 years at the time of inclusion, using binary logistic regression analysis. Study subjects came from a random population based sample and were included 1974–1992, whilst the echocardiography was performed 2002–2006. Results: After a mean follow-up time of 27 years, grade 2 or 3 diastolic dysfunction was detected in 34% (n = 89) of subjects. In univariate analyses (significance level 0.05), diastolic dysfunction was associated with age, sex, heart rate, systolic blood pressure, fasting insulin levels, 2-hour glucose levels, HOMA-2B, HOMA-2S, HOMA-2IR, and the time elapsed between inclusion and echocardiography. In multivariable analysis (significance level 0.20), sex (odds ratio (OR) = 6.08 (95% confidence interval (CI), 1.26–29.25); p = 0.02), heart rate (OR = 1.02 (95% CI, 0.996–1.05); p = 0.1), HOMA-2B (OR = 1.01 (95% CI, 1.00–1.01); p = 0.051), and time span (OR = 1.84 (95% CI, 1.73–1.96); p = 0.01), remained significantly associated with diastolic dysfunction, whereas age was forced into the model (OR = 1.03 (95% CI, 0.96–1.11); p = 0.41). We did not detect any significant interactions between HOMA-2B and other variables in the prediction of diastolic dysfunction. Conclusions: In a binary logistic regression model adjusted for age, sex, and time, HOMA-2B was significantly associated with the development of grade 2 or 3 diastolic dysfunction. It is suggested that subjects with increased HOMA-2B values may be at greater cardiovascular risk.