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1. Why Not to Use the Handgrip Test in the Assessment of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes Mellitus?

Author

Körei AE, Kempler M, Istenes I, Vági OE, Putz Z, Horváth VJ, Keresztes K, Lengyel C, Tabák ÁG, Spallone V, and Kempler P

Subjects
Aged, Biomarkers blood, Cross-Sectional Studies, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 diagnosis, Diabetic Nephropathies blood, Diabetic Nephropathies etiology, Diabetic Nephropathies physiopathology, Female, Glycated Hemoglobin metabolism, Humans, Hypertension diagnosis, Hypotension, Orthostatic physiopathology, Male, Middle Aged, Patient Positioning, Predictive Value of Tests, Reflex, Reproducibility of Results, Respiratory Mechanics, Valsalva Maneuver, Autonomic Nervous System physiopathology, Blood Pressure, Cardiovascular System innervation, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 2 complications, Diabetic Nephropathies diagnosis, Hand Strength, Hypertension physiopathology, Neurologic Examination methods
Abstract

Objective: Historically, a set of 5 Cardiovascular Autonomic Reflex Tests (CARTs) were considered to be the gold standard in the assessment of Cardiovascular Autonomic Neuropathy (CAN). However, measuring diastolic Blood Pressure (BP) response to sustained handgrip is omitted in recent guidelines. We aimed to assess the association between the handgrip and the other 4 tests as well as to identify determinants of the handgrip test results in diabetic patients., Patients and Methods: 353 patients with diabetes (DM) were recruited (age: 60.2±7.4 years; female: 57.2%; BMI: 29.3±2.1 kg/m2; DM duration: 15.6±9.9 years; HbA1c: 7.8±1.4% (66 mmol/mol); with type 1 DM: 18.1%). CAN was assessed by 5 CARTs: the deep breathing test, Valsalva ratio, 30/15 ratio, handgrip and orthostatic hypotension test., Results: Sensitivity and specificity of the handgrip test in the diagnosis of definite CAN were 24.6% (95%CI 17.7-33.1%) and 79.4% (95%CI 73.3-84.4%), respectively. Results of the handgrip test did not show any association with those of the deep-breathing test (y=0.004, p=0.563), 30/15 ratio (y=0.282, p=0.357), Valsalva ratio (y=-0.058, p=0.436) and orthostatic hypotension (y=-0.026, p=0.833). Handgrip test abnormality showed an independent association with higher initial diastolic BP (OR 1.05, p=0.0009) and an independent inverse association with the presence of hypertension (OR=0.42, p=0.006)., Conclusion: Our data confirm that the handgrip test should no longer be part of the cardiovascular autonomic testing being highly dependent on hypertensive status and baseline diastolic BP. Exaggerated exercise pressor response is proposed as putative mechanism for the inverse association between abnormal results of the handgrip test and hypertension. Adequate CARTs are important to allow their use in clinical trials and for the prevention of DM-associated complications by initiating early treatment.

Published
2017
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2. Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance.

Author

Putz Z, Németh N, Istenes I, Martos T, Gandhi RA, Körei AE, Hermányi Z, Szathmári M, Jermendy G, Tesfaye S, Tabák ÁG, and Kempler P

Subjects
Autonomic Nervous System Diseases etiology, Blood Glucose metabolism, Body Mass Index, Case-Control Studies, Female, Glucose Intolerance complications, Glycated Hemoglobin metabolism, Heart Rate physiology, Humans, Male, Middle Aged, Autonomic Nervous System Diseases physiopathology, Blood Pressure physiology, Circadian Rhythm physiology, Glucose Intolerance physiopathology
Abstract

Aims: To assess circadian blood pressure variability in people with impaired glucose tolerance and a healthy control population., Methods: Seventy-five people with impaired glucose tolerance and 40 healthy volunteers (frequency matched on 10-year age bands and sex) underwent a detailed neurological assessment. Autonomic neuropathy was detected by the five standard cardiovascular autonomic tests and heart rate variability was characterized by the triangle index. Diurnal indices were assessed by 24-h ambulatory blood pressure monitoring. Systolic and diastolic diurnal indices were defined as: (mean daytime blood pressure - mean night-time blood pressure) × 100/mean daytime blood pressure., Results: Mean 24-h systolic and diastolic blood pressure was significantly higher in the group with impaired glucose tolerance compared with the control group [126 ± 12 (mean ± SD) vs. 117 ± 10, 75 ± 7 vs. 71 ± 6 mmHg, both P < 0.05). Systolic and diastolic diurnal indices and heart rate variability triangular index were significantly lower in people with impaired glucose tolerance compared with control subjects (9.1 ± 7.8 vs. 13.2 ± 5.4, 14.5 ± 9.7 vs. 18.4 ± 7.1 mmHg, 28.0 ± 8.4 vs. 39.5 ± 9.3, all P < 0.05). Differences in mean diastolic blood pressure, heart rate variability triangular index and the frequency of non-dippers between those with impaired glucose tolerance and control subjects seemed to be independent of BMI and the presence of cardiovascular autonomic neuropathy, as simultaneous adjustment for BMI and cardiovascular autonomic neuropathy had no major effect on the results., Conclusion: Our data suggest that people with impaired glucose tolerance have increased diastolic blood pressure and abnormal circadian blood pressure regulation, independent of obesity and the presence of cardiovascular autonomic neuropathy., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

Published
2013
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3. Methods of investigation for cardiac autonomic dysfunction in human research studies.

Author

Bernardi L, Spallone V, Stevens M, Hilsted J, Frontoni S, Pop-Busui R, Ziegler D, Kempler P, Freeman R, Low P, Tesfaye S, and Valensi P

Subjects
Cardiovascular Diseases physiopathology, Diagnostic Tests, Routine, Humans, Sensitivity and Specificity, Autonomic Nervous System physiopathology, Baroreflex physiology, Blood Pressure physiology, Cardiovascular Diseases diagnosis, Diabetic Neuropathies diagnosis, Heart Rate physiology
Abstract

This consensus document provides evidence-based guidelines regarding the evaluation of diabetic cardiovascular autonomic neuropathy (CAN) for human research studies; the guidelines are the result of the work of the CAN Subcommittee of the Toronto Diabetic Neuropathy Expert Group. The subcommittee critically reviewed the limitations and strengths of the available diagnostic approaches for CAN and the need for developing new tests for autonomic function. It was concluded that the most sensitive and specific approaches currently available to evaluate CAN in clinical research are: (1) heart rate variability, (2) baroreflex sensitivity, (3) muscle sympathetic nerve activity, (4) plasma catecholamines, and (5) heart sympathetic imaging. It was also recommended that efforts should be undertaken to develop new non-invasive and safe CAN tests to be used in clinical research, with higher sensitivity and specificity, for studying the pathophysiology of CAN and evaluating new therapeutic approaches., (Copyright © 2011 John Wiley & Sons, Ltd.)

Published
2011
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4. Blood pressure response to standing in the diagnosis of autonomic neuropathy: are initial (supine) values of importance.

Author

Istenes I, Keresztes K, Tündik A, Hermányi Z, Putz Z, Vargha P, Kertész T, Emery C, Gandhi R, Tesfaye S, and Kempler P

Subjects
Adult, Case-Control Studies, Female, Humans, Male, Supine Position physiology, Systole physiology, Autonomic Nervous System Diseases diagnosis, Blood Pressure physiology, Diabetic Neuropathies diagnosis
Published
2007
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5. Coronary flow reserve, insulin resistance and blood pressure response to standing in patients with normoglycaemia: is there a relationship?

Author

Nemes A, Lengyel C, Forster T, Várkonyi TT, Takács R, Nagy I, Kempler P, Lonovics J, and Csanády M

Subjects
Adult, Blood Glucose metabolism, Echocardiography, Female, Homeostasis physiology, Humans, Male, Middle Aged, Blood Pressure physiology, Coronary Circulation physiology, Insulin Resistance physiology
Abstract

Aims: To establish the relationships between coronary flow reserve, cardiovascular autonomic function, and insulin resistance characterized by the homeostasis model assessment insulin resistance score in patients with normal carbohydrate metabolism according to the World Health Organization (WHO) and American Diabetes Association (ADA) criteria, and with morphologically normal epicardial coronary arteries., Methods: Twenty-five patients [12 women and 13 men, mean (sd) age: 53 +/- 11 years] with normal coronary angiography were enrolled into the study. Coronary flow reserve was measured during stress transoesophageal echocardiography. Autonomic dysfunction was assessed by means of five standard cardiovascular reflex tests. The fasting serum glucose and insulin levels were determined and the homeostasis assessment model insulin resistance score was calculated., Results: In patients with normal carbohydrate metabolism, negative correlations were observed between the coronary flow reserve and both the serum insulin level (r = -0.445, P = 0.026) and the homeostasis assessment model insulin resistance score (r = -0.449, P = 0.024). The systolic blood pressure response to standing also correlated with the coronary flow reserve (r = -0.519, P = 0.011). The heart rate response to deep breathing, the Valsalva ratio, the 30/15 ratio and the sustained handgrip test results were not correlated with the coronary flow reserve., Conclusions: Our data suggest the possible role of insulin resistance and early sympathetic nerve dysfunction in the development of decreased coronary flow reserve in patients without diabetes mellitus or impaired glucose tolerance.

Published
2005
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7. Peripheral and Autonomic Neuropathy Status of Young Patients With Type 1 Diabetes Mellitus at the Time of Transition From Pediatric Care to Adult-Oriented Diabetes Care

Author

Anna Vágvölgyi, Ágnes Maróti, Mónika Szűcs, Csongor Póczik, Dóra Urbán-Pap, István Baczkó, Attila Nemes, Éva Csajbók, Krisztián Sepp, Péter Kempler, Andrea Orosz, Tamás Várkonyi, and Csaba Lengyel

Subjects
health care transition, autonomic neuropathy, type 1 diabetes mellitus, peripheral sensory neuropathy, blood pressure, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

IntroductionThe prevalence of neuropathic lesions in young patients with type 1 diabetes mellitus (T1DM) at the time of transition from pediatric care to adult-oriented diabetes care is poorly studied. A comparative study with healthy volunteers to assess the possible neuropathic condition of this special population and to identify the potential early screening needs has not been performed yet. The results may provide important feedback to pediatric diabetes care and a remarkable baseline reference point for further follow up in adult diabetes care.Patients and MethodsTwenty-nine young patients with T1DM [age: 22.4 ± 2.9 years; HbA1c: 8.5 ± 2.1%, diabetes duration: 12.2 ± 5.8 years; (mean ± SD)] and 30 healthy volunteers (age: 21.5 ± 1.6 years; HbA1c: 5.3 ± 0.3%) were involved in the study. Autonomic function was assessed by standard cardiovascular reflex tests. Complex peripheral neuropathic testing was performed by Neurometer®, Neuropad®-test, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests.ResultsT1DM patients had significantly higher diastolic blood pressure than controls (80 ± 9 vs. 74 ± 8 mmHg, p < 0.01), but there was no significant difference in systolic blood pressure (127 ± 26 vs. 121 ± 13 mmHg). Cardiovascular reflex tests had not revealed any significant differences between the T1DM patients and controls. No significant differences with Neurometer®, Neuropad®-test, and Monofilament® were detected between the two groups. The vibrational sensing on the radius on both sides was significantly impaired in the T1DM group compared to the controls with Rydel-Seiffer tuning fork test (right: 7.5 ± 1.0 vs. 7.9 ± 0.3; left: 7.5 ± 0.9 vs. 7.9 ± 0.3, p < 0.05). The Tiptherm®-test also identified a significant impairment in T1DM patients (11 sensing failures vs. 1, p < 0.001). In addition, the neuropathic complaints were significantly more frequently present in the T1DM patient group than in the controls (9 vs. 0, p < 0.01).ConclusionIn this young T1DM population, cardiovascular autonomic neuropathy and cardiac morphological alterations could not be found. However, Rydel-Seiffer tuning fork and Tiptherm®-tests revealed peripheral sensory neurological impairments in young T1DM patients at the time of their transition to adult diabetes care.

Published
2021
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9. Protein intake and urinary albumin excretion rates in the EURODIAB IDDM Complications Study

Author

Toeller, M, Buyken, A, Heitkamp, G, Brämswig, S, Mann, J, Milne, R, Gries, F. A, Keen, H, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Roussipenessi, D, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Strachinariu, R, Nicolau, A, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, B, Cronin, Cc, Humphreys, M, Klischan, A, Forst, T, Schumacher, W, Rottiers, R, Priem, H, Deschoolmeester, Mj, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Eltedewever, Bm, Nunescorrea, J, Boavida, J, Carvalho, R, Afonso, Mj, Monteiro, M, Mitchell, DAVID ROSS, Jepson, E, Mchardyyoung, S, Fuller, Jh, Betteridge, Dj, Milne, M, Thompson, T, Michel, G, Wirion, R, Paquet, S, Hornick, H, Boulton, Ajm, Ashe, H, Fernando, Djs, Curwell, J, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Marchi, Manuel, Mehnert, H, Nuber, A, Janka, H, Nichting, M, Standl, E, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Baclet, N, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, R, Nannipieri, M, Manfredi, S, Bertolotto, A, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Careddu, G, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, Sivieri, P., R, Carta, Q, Petraroli, G, Papazoglu, N, Goutzourela, M, Manes, C, Bensoussan, D, Fallas, Mc, Fallas, P, Dhanaeus, C, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Branzi, P, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Strohner, H, Just, M, Walford, S, Wardle, Henio, Ev, S, Cooke, H, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, Vrhovac, V., Toeller, M, Buyken, A, Heitkamp, G, Bramswig, S, Mann, J, Milne, R, Gries, Fa, Keen, H, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Roussipenessi, D, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Strachinariu, R, Nicolau, A, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, B, Cronin, Cc, Humphreys, M, Klischan, A, Forst, T, Schumacher, W, Rottiers, R, Priem, H, Deschoolmeester, Mj, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Eltedewever, Bm, Nunescorrea, J, Boavida, J, Carvalho, R, Afonso, Mj, Monteiro, M, David, R, Jepson, E, Mchardyyoung, S, Fuller, Jh, Betteridge, Dj, Milne, M, Thompson, T, Michel, G, Wirion, R, Paquet, S, Hornick, H, Boulton, Ajm, Ashe, H, Fernando, Dj, Curwell, J, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Marchi, M, Mehnert, H, Nuber, A, Janka, H, Nichting, M, Standl, E, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Baclet, N, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, R, Nannipieri, M, Manfredi, S, Bertolotto, A, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Careddu, G, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglu, N, Goutzourela, M, Manes, C, Bensoussan, D, Fallas, Mc, Fallas, P, Dhanaeus, C, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Branzi, P, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Strohner, H, Just, M, Walford, S, Wardle, Ev, Henio, S, Cooke, H, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, and Vrhovac, V

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Urinary system, Physiology, Albuminuria, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Diabetic Nephropathies, Dietary Proteins, Europe, Female, Humans, Middle Aged, Nephropathy, Protein intake, urinary albumin, Diabetic nephropathy, Excretion, Diabetes mellitus, Internal medicine, Diabetes Mellitus, Internal Medicine, Medicine, Proteinuria, business.industry, medicine.disease, Endocrinology, Blood pressure, medicine.symptom, business, Type 1, Kidney disease
Abstract

For people with insulin-dependent diabetes mellitus (IDDM) renal disease represents a life-threatening and costly complication. The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to determine the prevalence of renal complications and putative risk factors in stratified samples of European individuals with IDDM. The present study examined the relationship between dietary protein intake and urinary albumin excretion rate (AER). Food intake was assessed centrally by a standardized 3-day dietary record. Urinary AER was determined in a central laboratory from a timed 24-h urine collection. Complete data were available from 2696 persons with IDDM from 30 centres in 16 European countries. In individuals who reported protein consumption less than 20 % of total food energy intake, mean AER was below 20 μg/min. In those in whom protein intake constituted more than 20 %, mean AER increased, a trend particularly pronounced in individuals with hypertension and/or poor metabolic control. Trends reached statistical significance for intakes of total protein (% of energy, p = 0.01) and animal protein (% of energy, p = 0.02), while no association was seen for vegetable protein (p = 0.83). These findings support the current recommendation for people with diabetes not to exceed a protein intake of 20 % of total energy. Monitoring and adjustment of dietary protein appears particularly desirable for individuals with AER exceeding 20 μg/min (approximately 30 mg/24 h), especially when arterial pressure is raised and/or diabetic control is poor. [Diabetologia (1997) 40: 1219–1226]

Published
1997

10. Fibrinogen and von Willebrand factor in IDDM: relationships to lipid vascular risk factors, blood pressure, glycaemic control and urinary albumin excretion rate: the EURODIAB IDDM Complications Study

Author

Greaves, M, Malia, Rg, Goodfellow, K, Mattock, M, Stevens, Lk, Stephenson, Jm, Fuller, Jh, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Giorgino, R, Cignarelli, M, Decicco, Ml, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, D, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, Jb, Cronin, Cc, Whyte, Ae, Cleary, Pe, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Rottiers, R, Priem, H, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Brachter, J, Nunescorrea, J, Boavida, J, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Djs, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Janka, Hu, Nuber, A, Mehnert, H, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Crepaldi, G, Nosadini, R, Segato, T, Midena, E, Cipollina, Mr, Fedele, D, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, Roberto, Nannipieri, Monica, Manfredi, S, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Perin, Pc, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Skazagar, G, Kontogiannis, I, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Hughes, S, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, Keen, H, Navelesi, R, Sjolie, Ak, Viberti, Gc, Ward, J, Partridge, T, John, Wg, Collins, A, Dredge, A, Sharp, R, Kohner, E, Aldington, S, Cockley, S., Greaves, M, Malia, Rg, Goodfellow, K, Mattock, M, Stevens, Lk, Stephenson, Jm, Fuller, Jh, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Giorgino, R, Cignarelli, M, Decicco, Ml, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, D, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, Jb, Cronin, Cc, Whyte, Ae, Cleary, Pe, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Rottiers, R, Priem, H, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Brachter, J, Nunescorrea, J, Boavida, J, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Dj, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, Francesco, Janka, Hu, Nuber, A, Mehnert, H, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Crepaldi, G, Nosadini, R, Segato, T, Midena, E, Cipollina, Mr, Fedele, D, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, R, Nannipieri, M, Manfredi, S, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Perin, Pc, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Skazagar, G, Kontogiannis, I, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Hughes, S, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, Keen, H, Navelesi, R, Sjolie, Ak, Viberti, Gc, Ward, J, Partridge, T, John, Wg, Collins, A, Dredge, A, Sharp, R, Kohner, E, Aldington, S, and Cockley, S.

Subjects
Blood Glucose, Male, Glycated Hemoglobin A, Endocrinology, Diabetes and Metabolism, Blood lipids, Blood Pressure, Fibrinogen, Body Mass Index, Risk Factors, biology, Smoking, von Willebrand factor, fibrinogen, The EURODIAB IDDM Study, Europe, Cholesterol, Cardiovascular Diseases, Female, medicine.symptom, medicine.drug, Type 1, Adult, medicine.medical_specialty, HDL, LDL, Von Willebrand factor, Internal medicine, Diabetes mellitus, von Willebrand Factor, Internal Medicine, medicine, Diabetes Mellitus, Humans, Albuminuria, Cholesterol, HDL, Cholesterol, LDL, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Diabetic Angiopathies, Triglycerides, Glycated Hemoglobin, business.industry, Vascular disease, medicine.disease, Blood pressure, Endocrinology, biology.protein, Microalbuminuria, business
Abstract

The interrelationships between fibrinogen, von Willebrand factor, a marker of vascular endothelial cell damage, and serum lipids were explored in well-characterised subjects with insulin-dependent diabetes mellitus. The 2091 subjects were enrolled into a cross-sectional, clinic-based study of complications, from 16 European countries: the EURODIAB IDDM Complications study. The anticipated significant relationships between both plasma fibrinogen and plasma von Willebrand factor concentrations and age and glycaemic control, and between fibrinogen and body mass index, were noted. Fibrinogen, adjusted for age and glycated haemoglobin concentration, was also related to smoking habits and was higher in the quartiles with highest systolic and diastolic blood pressures. There was a clustering of vascular risk factors, with a positive relationship between plasma fibrinogen and serum triglyceride concentrations in both genders and between fibrinogen and total cholesterol in males. An inverse relationship between fibrinogen and high density lipoprotein cholesterol was also apparent in males. A prominent feature was a positive relationship between both fibrinogen and von Willebrand factor and albumin excretion rate (p < 0.001 and p < 0.003 respectively) in those with retinopathy but not in these without this complication. In view of previous observations on blood pressure and albuminuria in these subjects the findings are consistent with the hypothesis that microalbuminuria and increased plasma von Willebrand factor are due to endothelial cell perturbation in response to mildly raised blood pressure in subjects with retinopathy. Fibrinogen may also contribute to microvascular disease and its relationships to lipid vascular risk factors suggest a possible pathogenic role in arterial disease in diabetes.

Published
1997

11. Cardiovascular disease and its risk factors in IDDM in Europe

Author

Koivisto VA, Stevens LK, Mattock M, Ebeling P, Muggeo M, Stephenson J, IdziorWalus B, Karamanos B, Tountas C, Kofinis A, Petrou K, Katsilambros N, Cignarelli M, Giorgino R, DeGeco ML, Ramunni I, IonescuTirgoviste C, Iosif CM, Pitei C, Buligescu S, Tamas G, Kerenyi Z, Ahmed AM, Toth J, Kempler P, Muntoni S, Songini M, Stabilini M, Fossarello M, Pintus S, Ferris B, Cronin CC, Toeller M, Klischan A, Forst T, Gries FA, Wagener W, Rottiers R, Priem H, Sinisalo M, Solnica B, SzopinskaCiba L, Solnica K, Krans M, Lemkes HHPJ, Jansen JJ, NunesCorrea J, Rogado C, Boavida JM, Correia LG, Michel G, Wirion R, Boulton AJM, Ashe H, Fernando DJS, Pozza G, Slaviero G, Comi B, Fattor F, Janka HU, Nuber A, Mehnert H, BenSoussan D, Fallas MC, Fallas P, Jepson E, McHardyYoung S, Fuller JH, Betteridge DJ, Milne M, Crepaldi C, Nosadini R, Cathelineau G, Cathelineau BV, Jellal M, Grodner N, Feiss PG, Santeusanio F, Rosi G, Cagini C, Marino C, Navalesi R, Penno G, Miccoli R, Nannipieri M, Stefano M, Ghirlanda G, Controneo P, Manto A, Teodonio C, Minnella A, Ward JD, Tesfaye S, Mody C, Rudd C, Molinatti GM, Vitelli F, Porta M, Pagano GF, Estivi P, Sivieri R, Carta Q, Petraroli G, Papazoglou N, Manes G, Triantaphyllou G, Ioannides A, Cacciatori V, Bellavere F, Galante P, Gemma ML, Irsigler K, Abrahamian H, Gurdet C, Hornlein B, Willinger C, Walford S, Wardle EV, Roglic G, Resman Z, Metelko Z, Skrabalo Z, Keen H, Sjolie AK, Viberti GC, Ward J, John G, Collins A, Sharp R., BANDELLO , FRANCESCO, Koivisto, Va, Stevens, Lk, Mattock, M, Ebeling, P, Muggeo, M, Stephenson, J, Idziorwalus, B, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, C, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferris, B, Cronin, Cc, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Wagener, W, Rottiers, R, Priem, H, Sinisalo, M, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, M, Lemkes, Hhpj, Jansen, Jj, Nunescorrea, J, Rogado, C, Boavida, Jm, Correia, Lg, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Dj, Pozza, G, Slaviero, G, Comi, B, Fattor, F, Bandello, Francesco, Janka, Hu, Nuber, A, Mehnert, H, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Fuller, Jh, Betteridge, Dj, Milne, M, Crepaldi, C, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, R, Nannipieri, M, Stefano, M, Ghirlanda, G, Controneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, Keen, H, Sjolie, Ak, Viberti, Gc, Ward, J, John, G, Collins, A, and Sharp, R.

Subjects
medicine.medical_specialty, Cross-sectional study, Endocrinology, Diabetes and Metabolism, Population, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Cardiovascular disease, EURODIAB IDDM study, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Risk factor, education, Advanced and Specialized Nursing, education.field_of_study, business.industry, medicine.disease, 3. Good health, Endocrinology, Blood pressure, Albuminuria, Metabolic syndrome, medicine.symptom, business
Abstract

OBJECTIVE To study the prevalence of cardiovascular disease (CVD), its risk factors, and their associations in IDDM patients in different European countries. RESEARCH DESIGN AND METHODS The prevalence of CVD (a past history or electrocardiogram abnormalities) and its risk factors were examined in a cross-sectional study in 3,250 IDDM patients from 16 European countries (EURODIAB IDDM Complications Study). The patients were examined in 31 centers and were stratified between centers for age, sex, and duration of diabetes. The mean ± SD duration of diabetes was 14.7 ± 9.3 years. RESULTS The prevalence of CVD was 9% in men and 10% in women. The prevalence increased with age (from 6% in patients 15–29 years old to 25% in patients 45–59 years old) and with duration of diabetes. The between-center variation for the whole population was from 3 to 19%. In both sexes, fasting triglyceride concentration was higher and HDL cholesterol lower in those patients with CVD than in those without. In men, duration of diabetes was longer, waist-to-hip ratio greater, and hypertension more common in patients with CVD. In women, a greater BMI was associated with increased prevalence of CVD. There was no association between insulin dose, HbA1c level, age-adjusted rate of albumin excretion, or smoking status and CVD. Waist-to-hip ratio, particularly in men, was positively associated with age, age-adjusted HbA1c, prevalence of smoking, daily insulin dose, albumin excretion rate, and fasting triglyceride concentrations. CONCLUSIONS The overall prevalence of CVD in these IDDM patients was ∼ 10%, increasing with age and duration of diabetes and with a sixfold variation between different European centers. CVD prevalence was most strongly associated with elevated triglyceride and decreased HDL cholesterol concentrations. CVD was also associated with albuminuria, but when adjusted by age, this association vanished. Increasing waist-to-hip ratio was associated with a number of adverse characteristics, particularly in IDDM men, reflecting the metabolic syndrome previously described in other populations.

Published
1996

12. BLOOD-PRESSURE, RETINOPATHY AND URINARY ALBUMIN EXCRETION IN IDDM - THE EURODIAB IDDM COMPLICATIONS STUDY

Author

Stephenson, Jm, Fuller, Jh, Viberti, Gc, Sjolie, Ak, Navalesi, R, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Giorgino, R, Cignarelli, M, Decicco, M, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, D, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, Jb, Cronin, Cc, Whyte, Ae, Cleary, Pe, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Wagener, W, Rottiers, R, Priem, H, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Brachter, J, Nunescorrea, J, Boavida, J, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Djs, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Mehnert, H, Nuber, A, Janka, H, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Penno, G, Miccoli, Roberto, Nannipieri, Monica, Manfredi, S, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Perin, Pc, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Skazagar, G, Kontogiannis, I, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Hughes, S, Roglic, G, Resman, Z, Metelko, Z, and Skrabalo, Z.

Subjects
Adult, Male, medicine.medical_specialty, THE EURODIAB IDDM COMPLICATIONS STUDY, Endocrinology, Diabetes and Metabolism, Urology, Blood Pressure, Nephropathy, Diabetic nephropathy, Diastole, Reference Values, Risk Factors, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Confidence Intervals, Prevalence, Albuminuria, Humans, Age of Onset, Proteinuria, Diabetic Retinopathy, business.industry, Diabetic retinopathy, medicine.disease, Europe, Endocrinology, Blood pressure, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Female, medicine.symptom, business, Retinopathy
Abstract

Several studies have shown an association between blood pressure and nephropathy, but few have been large enough to examine whether, or how, this relation is influenced by retinopathy. We have therefore examined the independent relations of blood pressure to urinary albumin excretion and retinopathy in a cross-sectional observational study of over 3000 insulin-dependent diabetic patients (the EURODIAB IDDM Complications Study). The relation of blood pressure to urinary albumin excretion differed strikingly between patients with (46%) and without (54%) retinopathy. In those with retinopathy, mean urinary albumin excretion rate was normal (20 micrograms/min) below median diastolic pressure (75 mmHg) and increased steeply (p0.001) with blood pressure above this level. However, in patients without retinopathy, mean albumin excretion rate was normal across the range of diastolic pressure. This finding could not be explained by differences in glycaemic control or duration of diabetes between patients with and without retinopathy. These data identify a subgroup of patients whose high risk of nephropathy may reflect abnormal renal vulnerability to mildly raised blood pressure. Retinopathy is a close correlate of this vulnerability. Detection of even mild retinopathy, together with raised blood pressure, may be important in assessing nephropathy risk.

Published
1995

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