Type 2 diabetes and HbA(1c) are independently associated with wider retinal arterioles: the Maastricht study.

Li W ，Schram MT ，Berendschot TTJM ，Webers CAB ，Kroon AA ，van der Kallen CJH ，Henry RMA ，Schaper NC ，Huang F ，Dashtbozorg B ，Tan T ，Zhang J ，Abbasi-Sureshjani S ，Ter Haar Romeny BM ，Stehouwer CDA ，Houben AJHM ... -  《-》

Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction: The Maastricht Study.

Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes ("ticking clock hypothesis"). Whether a similar phenomenon also applies to microvascular dysfunction is not known. We therefore tested the hypothesis that microvascular dysfunction is already present in prediabetes and is more severe in T2DM. To do so, we investigated the associations of prediabetes, T2DM, and measures of hyperglycemia with microvascular function measured as flicker light-induced retinal arteriolar dilation and heat-induced skin hyperemia. In the Maastricht Study, a T2DM-enriched population-based cohort study (n=2213, 51% men, aged [mean±standard deviation] 59.7±8.2 years), we determined flicker light-induced retinal arteriolar %-dilation (Dynamic Vessel Analyzer), heat-induced skin %-hyperemia (laser-Doppler flowmetry), and glucose metabolism status (oral glucose tolerance test; normal glucose metabolism [n=1269], prediabetes [n=335], or T2DM [n=609]). Differences were assessed with multivariable regression analyses adjusted for age, sex, body mass index, smoking, physical activity, systolic blood pressure, lipid profile, retinopathy, estimated glomerular filtration rate, (micro)albuminuria, the use of lipid-modifying and blood pressure-lowering medication, and prior cardiovascular disease. Retinal arteriolar %-dilation was (mean±standard deviation) 3.4±2.8 in normal glucose metabolism, 3.0±2.7 in prediabetes, and 2.3±2.6 in T2DM. Adjusted analyses showed a lower arteriolar %-dilation in prediabetes (B=-0.20, 95% confidence interval -0.56 to 0.15) with further deterioration in T2DM (B=-0.61 [-0.97 to -0.25]) versus normal glucose metabolism (P for trend=0.001). Skin %-hyperemia was (mean±standard deviation) 1235±810 in normal glucose metabolism, 1109±748 in prediabetes, and 937±683 in T2DM. Adjusted analyses showed a lower %-hyperemia in prediabetes (B=-46 [-163 to 72]) with further deterioration in T2DM (B=-184 [-297 to -71]) versus normal glucose metabolism (P for trend=0.001). In addition, higher glycohemoglobin A1c and fasting plasma glucose were associated with lower retinal arteriolar %-dilation and skin %-hyperemia in fully adjusted models (for glycohemoglobin A1c, standardized B=-0.10 [-0.15 to -0.05], P<0.001 and standardized B=-0.13 [-0.19 to -0.07], P<0.001, respectively; for fasting plasma glucose, standardized B=-0.09 [-0.15 to -0.04], P<0.001 and standardized B=-0.10 [-0.15 to -0.04], P=0.002, respectively). Prediabetes, T2DM, and measures of hyperglycemia are independently associated with impaired microvascular function in the retina and skin. These findings support the concept that microvascular dysfunction precedes and thus may contribute to T2DM-associated cardiovascular disease and other complications, which may in part have a microvascular origin such as impaired cognition and heart failure.

Sörensen BM ，Houben AJ ，Berendschot TT ，Schouten JS ，Kroon AA ，van der Kallen CJ ，Henry RM ，Koster A ，Sep SJ ，Dagnelie PC ，Schaper NC ，Schram MT ，Stehouwer CD ... -  《-》

Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study.

de Ritter R ，Sep SJS ，van der Kallen CJH ，van Greevenbroek MMJ ，de Jong M ，Vos RC ，Bots ML ，Reulen JPH ，Houben AJHM ，Webers CAB ，Berendschot TTJM ，Dagnelie PC ，Eussen SJPM ，Schram MT ，Koster A ，Peters SAE ，Stehouwer CDA ... -  《Cardiovascular Diabetology》

Retinal Vasculometry Associations with Cardiometabolic Risk Factors in the European Prospective Investigation of Cancer-Norfolk Study.

To examine associations between retinal vessel morphometry and cardiometabolic risk factors in older British men and women. Retinal imaging examination as part of the European Prospective Investigation into Cancer-Norfolk Eye Study. Retinal imaging and clinical assessments were carried out in 7411 participants. Retinal images were analyzed using a fully automated validated computerized system that provides novel measures of vessel morphometry. Associations between cardiometabolic risk factors, chronic disease, and retinal markers were analyzed using multilevel linear regression, adjusted for age, gender, and within-person clustering, to provide percentage differences in tortuosity and absolute differences in width. Retinal arteriolar and venular tortuosity and width. In all, 279 802 arterioles and 285 791 venules from 5947 participants (mean age, 67.6 years; standard deviation [SD], 7.6 years; 57% female) were analyzed. Increased venular tortuosity was associated with higher body mass index (BMI; 2.5%; 95% confidence interval [CI], 1.7%-3.3% per 5 kg/m2), hemoglobin A1c (HbA1c) level (2.2%; 95% CI, 1.0%-3.5% per 1%), and prevalent type 2 diabetes (6.5%; 95% CI, 2.8%-10.4%); wider venules were associated with older age (2.6 μm; 95% CI, 2.2-2.9 μm per decade), higher triglyceride levels (0.6 μm; 95% CI, 0.3-0.9 μm per 1 mmol/l), BMI (0.7 μm; 95% CI, 0.4-1.0 per 5 kg/m2), HbA1c level (0.4 μm; 95% CI, -0.1 to 0.9 per 1%), and being a current smoker (3.0 μm; 95% CI, 1.7-4.3 μm); smoking also was associated with wider arterioles (2.1 μm; 95% CI, 1.3-2.9 μm). Thinner venules were associated with high-density lipoprotein (HDL) (1.4 μm; 95% CI, 0.7-2.2 per 1 mmol/l). Arteriolar tortuosity increased with age (5.4%; 95% CI, 3.8%-7.1% per decade), higher systolic blood pressure (1.2%; 95% CI, 0.5%-1.9% per 10 mmHg), in females (3.8%; 95% CI, 1.4%-6.4%), and in those with prevalent stroke (8.3%; 95% CI, -0.6% to 18%); no association was observed with prevalent myocardial infarction. Narrower arterioles were associated with age (0.8 μm; 95% CI, 0.6-1.0 μm per decade), higher systolic blood pressure (0.5 μm; 95% CI, 0.4-0.6 μm per 10 mmHg), total cholesterol level (0.2 μm; 95% CI, 0.0-0.3 μm per 1 mmol/l), and HDL (1.2 μm; 95% CI, 0.7-1.6 μm per 1 mmol/l). Metabolic risk factors showed a graded association with both tortuosity and width of retinal venules, even among people without clinical diabetes, whereas atherosclerotic risk factors correlated more closely with arteriolar width, even excluding those with hypertension and cardiovascular disease. These noninvasive microvasculature measures should be evaluated further as predictors of future cardiometabolic disease.

Owen CG ，Rudnicka AR ，Welikala RA ，Fraz MM ，Barman SA ，Luben R ，Hayat SA ，Khaw KT ，Strachan DP ，Whincup PH ，Foster PJ ... -  《-》

Retinal microvascular associations with cardiometabolic risk factors differ by diabetes status: results from the UK Biobank.

The aim of the study was to examine the association of retinal vessel morphometry with BP, body composition and biochemistry, and to determine whether these associations differ by diabetes status. The UK Biobank ocular assessment included 68,550 participants aged 40-70 years who underwent non-mydriatic retinal photography, BP and body composition measurements, and haematological analysis. A fully automated image analysis program provided measurements of retinal vessel diameter and tortuosity. The associations between retinal vessel morphology and cardiometabolic risk factors by diabetes status were examined using multilevel linear regression, to provide absolute differences in vessel diameter and percentage differences in tortuosity (allowing for within-person clustering). A total of 50,233 participants (a reduction from 68,550) were included in these analyses. Overall, those with diabetes had significantly more tortuous venules and wider arteriolar diameters compared with those without. Associations between venular tortuosity and cardiometabolic risk factors differed according to diabetes status (p interaction <0.01) for total fat mass index, HbA1c, C-reactive protein, white cell count and granulocyte count. For example, a unit rise in white cell count was associated with a 0.18% increase (95% CI 0.05, 0.32%) in venular tortuosity for those without diabetes and a 1.48% increase (95% CI 0.90, 2.07%) among those with diabetes. For arteriolar diameter, significant interactions were evident for systolic BP, diastolic BP, mean arterial pressure (MAP) and LDL-cholesterol. For example, a 10 mmHg rise in systolic BP was associated with a -0.92 μm difference (95% CI -0.96 to -0.88 μm) in arteriolar diameter for those without diabetes, and a -0.58 μm difference (95% CI -0.76 to -0.41 μm) among those with diabetes. No interactions were observed for arteriolar tortuosity or venular diameters. We provide clear evidence of the modifying effect of diabetes on cardiometabolic risk factor associations with retinal microvascular architecture. These observations suggest the occurrence of preclinical disease processes, and may be a sign of impaired autoregulation due to hyperglycaemia, which has been suggested to play a pivotal role in the development of diabetes-related microvascular complications. The data supporting the results reported here are available through the UK Biobank ( https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access ).

Tapp RJ ，Owen CG ，Barman SA ，Strachan DP ，Welikala RA ，Foster PJ ，Whincup PH ，Rudnicka AR ，UK Biobank Eyes and Vision Consortium ... -  《-》