Health burden in type 2 diabetes and prediabetes in The Maastricht Study.

Mortality in type 2 diabetes, is determined not only by classical complications, but also by comorbidities, and is linked to hyperglycaemia and apparent even in prediabetes. We aimed to comprehensively investigate, in a population-based cohort, health burden defined as the presence of comorbidities in addition to classical complications and cardiometabolic risk factors, in not only type 2 diabetes but also prediabetes. Such population-based study has not been performed previously. Extensive phenotyping was performed in 3,410 participants of the population-based Maastricht Study (15.0% prediabetes and 28.6% type 2 diabetes) to assess presence of 17 comorbidities, six classical complications, and ten cardiometabolic risk factors. These were added up into individual and combined sum scores and categorized. Group differences were studied with multinomial regression analyses adjusted for age and sex. Individuals with type 2 diabetes and prediabetes, as compared to normal glucose metabolism (NGM), had greater comorbidities, classical complications, cardiometabolic risk factors and combined sum scores (comorbidities sum score ≥ 3: frequencies (95% CI) 61.5% (57.6;65.4) and 41.2% (36.5;45.9) vs. 25.4% (23.5;27.4), p-trend < 0.001; classical complications ≥ 2 (26.6% (23.1;30.1; P < 0.001 vs. NGM) and 10.1% (7.8;12.7; P = 0.065 vs NGM) vs. 8.0% (6.9;9.3)); cardiometabolic risk factors ≥ 6 (39.7% (35.9;43.4) and 28.5% (24.5;32.6) vs. 14.0% (12.5;15.6); p-trend < 0.001); combined ≥ 8 (66.6% (62.7;70.5) and 48.4% (43.7;53.1) vs. 26.0%(24.1;28.0), p-trend < 0.001). Type 2 diabetes and prediabetes health burden was comparable to respectively 32 and 14 years of ageing. Our population-based study shows, independently of age and sex, a considerable health burden in both type 2 diabetes and prediabetes, which to a substantial extent can be attributed to comorbidities in addition to classical complications and cardiometabolic risk factors. Our findings emphasize the necessity of comorbidities' awareness in (pre)diabetes and for determining the exact role of hyperglycaemia in the occurrence of comorbidities.

Measures of Left Ventricular Diastolic Function and Cardiorespiratory Fitness According to Glucose Metabolism Status: The Maastricht Study.

Background This cross-sectional study evaluated associations between structural and functional measures of left ventricular diastolic function and cardiorespiratory fitness (CRF) in a well-characterized population-based cohort stratified according to glucose metabolism status. Methods and Results Six hundred seventy-two participants from The Maastricht Study (mean±SD age, 61±9 years; 17.4% prediabetes and 25.4% type 2 diabetes mellitus) underwent both echocardiography to determine left atrial volume index, left ventricular mass index, maximum tricuspid flow regurgitation, average e' and E/e' ratio; and submaximal cycle ergometer test to determine CRF as maximum power output per kilogram body mass. Associations were examined with linear regression adjusted for cardiovascular risk and lifestyle factors, and interaction terms. After adjustment, in normal glucose metabolism but not (pre)diabetes, higher left atrial volume index (per 1 mL/m2), left ventricular mass index (per 1 g/m2.7), maximum tricuspid regurgitation flow (per 1 m/s) were associated with higher CRF (maximum power output per kilogram body mass; ß in normal glucose metabolism 0.015 [0.008-0.023], Pinteraction (pre)diabetes <0.10; 0.007 [-0.001 to 0.015], Pinteraction type 2 diabetes mellitus <0.10; 0.129 [0.011-0.246], Pinteraction >0.10; for left atrial volume index, left ventricular mass index, maximum tricuspid regurgitation flow, respectively). Furthermore, after adjustment, in all individuals, higher average E/e' ratio (per unit), but not average e', was associated with lower CRF (normal glucose metabolism -0.044 [-0.071 to -0.016]), Pinteraction >0.10). Conclusions In this population-based study, structural and functional measures of left ventricular diastolic function were independently differentially associated with CRF over the strata of glucose metabolism status. This suggests that deteriorating left ventricular diastolic function, although of small effect, may contribute to the pathophysiological process of impaired CRF in the general population. Moreover, the differential effects in these structural measures may be the consequence of cardiac structural adaptation to effectively increase CRF in normal glucose metabolism, which is absent in (pre)diabetes.

Associations of (pre)diabetes with right ventricular and atrial structure and function: the Maastricht Study.

BACKGROUNDS: The role of right ventricular (RV) and atrial (RA) structure and function, in the increased heart failure risk in (pre)diabetes is incompletely understood. The purpose of this study is to investigate the associations between (pre)diabetes and RV and RA structure and function, and whether these are mediated by left ventricular (LV) alterations or pulmonary pressure. METHODS: Participants of the Maastricht Study; a population-based cohort study (426 normal glucose metabolism (NGM), 142 prediabetes, 224 diabetes), underwent two-dimensional and tissue Doppler echocardiography. Multiple linear regression analyses with pairwise comparisons of (pre)diabetes versus NGM, adjusted for cardiovascular risk factors, and mediation analyses were used. RESULTS: In general, differences were small. Nevertheless, in individuals with prediabetes and diabetes compared to NGM; RA volume index was lower (both p < 0.01, ptrend < 0.01), RV diameter was lower (both p < 0.01, ptrend < 0.01) and RV length was significantly smaller in diabetes (p = 0.67 and p = 0.03 respectively, ptrend = 0.04), TDI S'RV was lower (p = 0.08 and p < 0.01 respectively, ptrend < 0.01), TDI E'RV was lower (p = 0.01 and p = 0.02 respectively, ptrend = 0.01) and TDI A'RV was lower (p < 0.01 and p = 0.07 respectively, ptrend = 0.04). Only the differences in RA volume index (7.8%) and RV diameter (6.2%) were mediated by the maximum tricuspid gradient, but no other LV structure and function measurements. CONCLUSIONS: (Pre)diabetes is associated with structural RA and RV changes, and impaired RV systolic and diastolic function, independent of cardiovascular risk factors. These associations were largely not mediated by indices of LV structure, LV function or pulmonary pressure. This suggests that (pre)diabetes affects RA and RV structure and function due to direct myocardial involvement.

Cross-Sectional Associations Between Cardiac Biomarkers, Cognitive Performance, and Structural Brain Changes Are Modified by Age.

Objective- NT-proBNP (N-terminal pro-B-type natriuretic peptide) and cardiac troponin T (cTNT) are associated with cognitive performance. Whether this extends to individuals <60 years of age is unclear. We investigated whether age modified the associations between NT-proBNP and cTNT and cognitive performance and structural brain changes. Approach and Results- In 3011 individuals (60±8 years; 49% women), NT-proBNP and cTNT, memory, information processing speed and executive functioning, grey matter (GM) and white matter, and white matter hyperintensity (WMH) volumes were determined. We used regression, adjusted for educational level, cardiovascular factors, and lifestyle factors, to test whether cross-sectional associations between biomarkers and cognitive performance and structural brain changes were modified by age (<60 versus ≥60 years). ≥60 years, higher NT-proBNP was associated with lower memory (ß [SD] per 10-fold higher level [95% confidence interval (CI)], -0.11 [-0.22 to -0.00]), information processing speed (-0.12 [95% CI, -0.21 to -0.03]), executive functioning (-0.12 [95% CI, -0.22 to -0.03]), and smaller GM (ß [mL] per 10-fold higher level, -6.89 [95% CI, -11.58 to -2.20]). Additionally, higher cTNT was associated with lower memory (-0.33 [95% CI, -0.53 to -0.12]) and information processing speed (-0.17 [95% CI, -0.3 to -0.01]); with smaller GM (-16.07 [95% CI, -24.90 to -7.24]) and greater WMH (10ß WMH per 10-fold higher level, 0.31 [95% CI, 0.10-0.52]). <60 years, NT-proBNP and cTNT were not associated with cognitive performance ( Pinteraction, <0.10). In contrast, higher NT-proBNP was associated with smaller GM (-7.43 [95% CI, -11.70 to -3.16]) and greater WMH (0.13 [95% CI, 0.01-0.25]; Pinteraction,>0.10). Higher cTNT was associated with greater WMH (0.18 [95% CI, -0.01 to 0.37]; Pinteraction,>0.10) but not with GM (0.07 [95% CI, -6.87 to 7.02]; Pinteraction, <0.10). Conclusions- Biomarkers of cardiac injury are continuously associated with structural brain changes in both older and younger individuals but with poorer cognitive performance only in older individuals. These findings stress the continuous nature of the heart-brain axis in the development of cognitive impairment.

The systolic-diastolic difference in carotid stiffness is increased in type 2 diabetes: The Maastricht Study.

OBJECTIVE: In type 2 diabetes (T2D), increased arterial stiffening results from accelerated arterial wall matrix remodeling. The associated structural alterations modify the pressure dependency of arterial stiffness, which can be quantified by the systolic-diastolic difference in carotid pulse wave velocity (δPWV). We evaluated the association between T2D and δPWV as marker for matrix remodeling and whether δPWV may contain additional information beyond carotid stiffness (cPWV). METHODS: In 746 individuals from The Maastricht Study, 415 with normal glucose metabolism; 126 with prediabetes; and 205 with T2D, carotid pulse wave velocity (cPWV) and δPWV were determined by ultrasonography and tonometry. Multiple linear regression analyses were used to investigate associations of glucose metabolism status (with normal glucose metabolism as reference) with cPWV and δPWV, adjusting for age, sex, mean arterial pressure, prior cardiovascular disease, estimated glomerular filtration rate and smoking, and δPWV or cPWV as appropriate. RESULTS: After adjustment for age, sex, mean arterial pressure, prior cardiovascular disease, estimated glomerular filtration rate and smoking, T2D was associated with greater cPWV [ß (95% confidence interval) 0.376 (0.119; 0.632)] and δPWV [0.301 (0.013; 0.589)]. After additional adjustment for δPWV or cPWV, associations of T2D with cPWV and δPWV were attenuated [0.294 (0.048; 0.539) and 0.173 (-0.103; 0.449), respectively]. Prediabetes was not associated with either cPWV or δPWV. CONCLUSION: The systolic-diastolic difference in carotid stiffness is increased in T2D, but not prediabetes. Importantly, the association was not abolished by carotid stiffness, which suggests that systolic-diastolic difference in carotid stiffness carries additional information regarding arterial matrix remodeling.