Intima-Media-Dicke (IMT) und das kardiovaskuläre Risiko bei Patienten mit Typ-1-Diabetes mellitus

Zusammenfassung

Ein wichtiger Surrogatparameter für das erhöhte kardiovaskuläre Krankheitsrisiko des Typ-1-Diabetes ist eine verbreiterte Intima-Media-Schicht (IMT). In Fortsetzung früherer Studien zur Wertigkeit kardiovaskulärer Risikofaktoren war es das Ziel, in dieser Querschnittsstudie an 310 gut charakterisierten Patienten mit Typ-1-Diabetes die Beziehungen der IMT zum kardiovaskulären Risiko und zur Morbidität zu untersuchen. Eine Einteilung der Studienpopulation in Tertilen erfolgte entsprechend der IMT: ≤ 0,06 (Gruppe 0, 120 Patienten): 0,05 ± 0,08; 0,065–0,075 (Gruppe I, 83 Patienten): 0,069 ± 0,029; ≥ 0,08 (Gruppe II, 107 Patienten): 0,094 ± 0,036. Die Studienkohorte hatte ein mittleres Alter von 50,7 Jahren, eine Diabetesdauer von 23,8 Jahren, einen HbA1c von 8,38 % und einen BMI von 27,2 kg / cm². Unter den 107 Patienten mit einer verbreiterten IMT (Gruppe II) waren 62 männliche Patienten (57,9 %, p < 0,01). Diese Patienten hatten ein mittleres Alter von 60,6 Jahren (p < 0,01), eine Diabetesdauer von 29,6 Jahren (p < 0,01), ein Diabetesmanifestationsalter von 30,9 Jahren (p < 0,01), einen BMI von 28,3 kg / cm² (p < 0,01), einen Bauchumfang von 101,9 cm (p < 0,01), einen mittleren systolischen RR von 127 mmHg (p < 0,01) und einen mittleren diastolischen RR von 71 mmHg (p < 0,01). Die Prävalenzen an Hypertonus (92,5 %, p < 0,01), früheren Rauchern (27,4 %, p < 0,05), proliferativer Retinopathie (28,2 %, p < 0,01), Makulopathie (19,0 %, p < 0,05), diabetischem Fußsyndrom (7,5 %, p < 0,05), Neuropathiesymtomen (52,9 %, p < 0,01), HLP (77,4 %, p < 0,01), KHK (30,3 %, p < 0,01) und pAVK (33,6 %, p < 0,01) waren erhöht. In den univariaten Korrelationen bestanden signifikante Beziehungen zu Alter, Diabetesdauer, Diabetesmanifestationsalter, Körpergewicht, BMI, Bauchumfang, Serumkreatinin und systolischem Blutdruck (für alle p < 0,01). Die multiple logistische Korrelation zeigte unabhängige signifikante Beziehungen der verdickten IMT zum männlichen Geschlecht (OR 3,0, p < 0,01), Alter (OR 1,20, p < 0,01), Bauchumfang (OR 1,05, p < 0,05), früheren Rauchen (OR 4,7, p < 0,01), pAVK (OR 4,14, p < 0,01) und Neuropathie (OR 0,12, p < 0,01). Die verbreiterte IMT verdeutlicht beim Typ-1-Diabetes ein erhöhtes kardiovaskuläres Risiko bei erhöhten klassischen und modifizierbaren Risikofaktoren und erhöhter kardiovaskulärer Morbidität. 

Abstract

Increased IMT is an important surrogate parameter for increased cardiovascular morbidity. In continuation of previous studies, it was the aim of present cross-sectional study to evaluate the relationship of IMT with cardiovascular risk and morbidity in a cohort of 310 well characterized type 1 diabetic patients. According to IMT, patients were divided into tertiles: ≤ 0.06 (group 0, 120 patients): 0.05 ± 0.08; 0.065 – 0.075 (group I, 83 patients): 0.069 ± 0.029; ≥ 0.08 (group II, 107 patients): 0.094 ± 0.036. The study population had a mean age of 50.7 years, diabetes duration of 23.8 years, HbA1c of 8.38 %, and BMI of 27.2 kg / cm². Among the 107 patients of group II 62 patients were of male sex (57.9 %, p < 0.01). These patients were characterized by a mean age of 60.6 years (p < 0.01), mean diabetes duration of 29.6 years (p < 0.01), mean age of disease manifestation of 30.9 years (p < 0.01), BMI of 28.3 (p < 0.01), mean waist circumference of 101.9 cm (p < 0.01), mean systolic BP of 127 mmHg (p < 0.01), mean diastolic BP of 71 mmHg (p < 0.01). There were increased prevalences of hypertension (92.5 %, p < 0.01), smoking history (27.4 %, p < 0.05), proliferative retinopathy (28.2 %, p < 0.01), maculopathy (19.0 %, p < 0.05), diabetic foot syndrome (7.5 %, p < 0.05), diabetic neuropathy (52.9 %, p < 0.01), hyperlipoproteinemia (77.4 %, p < 0.01), coronary artery disease (30.3 %, p < 0.01), and peripheral vascular disease (33.6 %, p < 0.01). As shown by univariate correlation analysis (Spearman’ Rho) IMT was significantly related to age, diabetes duration, age of diabetes manifestation, body weight, BMI, waist circumference, serum creatinine and systolic blood pressure (for all p < 0.01). In multiple logistic regression analysis IMT was independently associated with male sex (OR 3.0, p < 0.01), age (OR 1.2, p < 0.01), waist circumference (OR 1.05, p < 0.05), smoking history (OR 4.7, p < 0.01), peripheral arterial disease (OR 4.1, p < 0.01), and neuropathy (OR 0.12, p < 0.01). In type 1 diabetes, increased IMT was found to be associated with cardiovascular risk as indicated by both increased concentrations of classic and modifiable atherosclerosis risk factors, and cardiovascular morbidity. 

Schlüsselwörter

Intima-Media-Dicke - Typ-1-Diabetes mellitus - kardiovaskuläres Risiko - kardiovaskuläre Erkrankungen

Key words

intima-media-thickness - type 1 diabetes mellitus - cardiovascular risk - cardiovascular morbidity

Literatur

• 1 Krolewski A S, Kosinski E J, Warram J H et al. Magnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus.  Am J Cardiol. 1987;  59 750-755
• 2 Libby P, Nathan D M, Abraham K et al. Report of the National Heart, Lung, and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases Working Group on Cardiovascular Complications of Type 1 Diabetes Mellitus.  Circulation. 2005;  111 3489-3493
• 3 Orchard T J, Costacou T, Kretowski A et al. Type 1 diabetes and coronary artery disease.  Diabetes Care. 2006;  29 2528-2538
• 4 Soedamah-Muthu S S, Fuller J H, Mulnier H E et al. High risk of cardiovascular disease in patients with type 1 diabetes in the U.K.: a cohort study using the general practice research database.  Diabetes Care. 2006;  29 798-804
• 5 Krolewski A S, Warram J H, Christlieb A R et al. The changing natural history of nephropathy in type 1 diabetes.  Am J Med. 1985;  78 785-794
• 6 Tuomilehto J, Borch-Johnsen K, Molarius A et al. Incidence of cardiovascular disease in type 1 (insulin-dependent) diabetic subjects with and without diabetic nephropathy in Finland.  Diabetologia. 1998;  41 784-790
• 7 Retnakaran R, Zinman B. Type 1 diabetes, hyperglycemia and the heart.  Lancet. 2008;  371 1790-1799
• 8 Beckman J A, Creager M A, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management.  JAMA. 2002;  287 2570-2581
• 9 Vinik A I, Maser R E, Mitchell B D et al. Diabetic autonomic neuropathy.  Diabetes Care. 2003;  26 1553-1579
• 10 Maser R E, Mitchell B D, Vinik A I et al. The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis.  Diabetes Care. 2003;  26 1895-1901
• 11 Orchard T J, Lloyd C E, Maser R E et al. Why does diabetic autonomic neuropathy predict IDDM mortality? An analysis from the Pittsburgh Epidemiology of Diabetes Complications Study.  Diabetes Res Clin Pract. 1996;  34 (suppl) 165-171
• 12 Poornima I G, Parikh P, Shannon R P. Diabetic cardiomyopathy: the search for a unifying hypothesis.  Circ Res. 2006;  98 596-605
• 13 Boudina S, Abel E D. Diabetic cardiomyopathy revisited.  Circulation. 2007;  115 3213-3223
• 14 Soedamah-Muthu S S, Fuller J H, Mulnier H E et al. All-cause mortality rates in patients with type 1 diabetes mellitus compared with a non-diabetic population from the UK general practice research database, 1992–1999.  Diabetologia. 2006;  49 660-666
• 15 Laing S P, Swerdlow A J, Slater S D et al. Mortality from heart disease in a cohort of 23 000 patients with insulin-treated diabetes.  Diabetologia. 2003;  46 760-765
• 16 Dahl-Jorgensen K, Larsen J R, Hanssen K F. Atherosclerosis in childhood and adolescent type1 diabetes: early disease, early treatment?.  Diabetologia. 2005;  48 1445-1453
• 17 Larsen J, Brekke M, Sandvik L et al. Silent coronary atheromatosis in type 1 diabetic patients and its relation to long-term glycemic control.  Diabetes. 2002;  51 2637-2641
• 18 Valsania P, Zarich S W, Kowalchuk G J et al. Severity of coronary artery disease in young patients with insulin-dependent diabetes mellitus.  Am Heart J. 1991;  122 695-700
• 19 Pajunen P, Taskinen M R, Nieminen M S et al. Angiographic severity and extent of coronary artery disease in patients with type 1 diabetes mellitus.  Am J Cardiol. 2000;  86 1080-1085
• 20 Nathan D M, Cleary P A, Backlund J Y et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes.  N Engl J Med. 2005;  353 2643-2653
• 21 Cleary P A, Orchard T J, Genuth S et al. The effect of intensive glycemic treatment on coronary artery calcification in type 1 diabetic participants of the Diabetes Control and Complications Trial / Epidemiology of Diabetes Interventions and Complications (DCCT / EDIC) Study.  Diabetes. 2006;  55 3556-3565
• 22 Lehto S, Rönnemaa T, Pyörälä K et al. Poor glycemic control predicts coronary heart disease events in patients with type 1 diabetes without nephropathy.  Arterioscler Thromb Vasc Biol. 1999;  19 1014-1019
• 23 Larsen J R, Brekke M, Bergengen L et al. Mean HbA1c over 18 years predicts carotid intima media thickness in women with type 1 diabetes.  Diabetologia. 2005;  48 776-779
• 24 Nathan D M, Lachin J, Cleary P et al. Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus.  N Engl J Med. 2003;  348 2294-2303
• 25 Orchard T J, Olson J C, Erbey J R et al. Insulin-resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study.  Diabetes Care. 2003;  26 1374-1379
• 26 Zander E, Heinke P, Allwardt C et al. Zur Bedeutung des Hypertonus bei Typ-1-diabetischen Patienten mit Normoalbuminurie.  Diabetes und Stoffwechsel. 2004;  13 131-138
• 27 Reindel J, Zander E, Heinke P et al. Metabolisches Syndrom bei Patienten mit Diabetes mellitus Typ 1: Auswirkungen auf das kardiovaskuläre Risikoprofil und die kardiovaskuläre Morbidität.  Herz. 2004;  29 463-469
• 28 Zander E, Allwardt C, Heinke P et al. Das kardiovaskuläre Risiko des Typ1-Diabetes: Koronare Herzkrankheit und periphere arterielle Durchblutungsstörungen.  Diabetes und Stoffwechsel. 2005;  14 119-126
• 29 Standl E, Tschöpe D. Diabetes mellitus und Herz. Praxisleitlinien der DDG.  Diabetes und Stoffwechsel. 2002;  11 (Suppl. 2) 22-24
• 30 Haslbeck M. Diagnose und Therapie der sensomotorischen diabetischen Neuropathie.  Diabetes und Stoffwechsel. 2002;  11 (Suppl. 2) 25-27
• 31 Haslacher C. Diabetische Nephropathie.  Diabetes und Stoffwechsel. 2002;  11 (Suppl. 2) 17-19
• 32 Deckert T, Poulsen J E, Larsen M. Prognosis of diabetes with diabetes onset before the age of thirty-one. II. Factors influencing the prognosis.  Diabetologia. 1978;  14 371-377
• 33 Dorman J S, Laporte R E, Kuller L H et al. The Pittsburgh Insulin-Dependent Diabetes Mellitus (IDDM) Morbidity and Mortality Study: mortality results.  Diabetes. 1984;  33 271-276
• 34 Moss S E, Klein R, Klein B E. Cause-specific mortality in a population-based study of diabetes.  Am J Public Health. 1991;  81 1158-1162
• 35 Bosnyak Z, Nishimura R, Hagan Hughes M et al. Excess mortality in black compared with white patients with type 1 diabetes: an examination of underlying causes.  Diabet Med. 2005;  22 1636-1641
• 36 Diabetes Epidemiology Research International Mortality Study Group . International evaluation of cause-specific mortality in IDDM.  Diabetes Care. 1991;  14 55-60
• 37 Andersen A R, Christiansen J S, Andersen J K et al. Diabetic nephropathy in type 1 (insulin-dependent) diabetes: an epidemiological study.  Diabetologia. 1983;  25 496-501
• 38 Maahs D M, Rewers M. Mortality and renal disease in type 1 Diabetes mellitus – Progress made, more to be done.  J Clin Endocrinol Metab. 2006;  91 3757-3759
• 39 Pambianco G, Costacou T, Ellis D et al. The 30-year natural history of type 1 diabetes complications: the Pittsburgh Epidemiology of Diabetes Complications Study experience.  Diabetes. 2006;  55 1463-1469
• 40 Stadler M, Auinger M, Anderwald C et al. Long-term mortality and incidence of renal dialysis and transplantation in type 1 Diabetes mellitus.  J Clin Endocrinol Metab. 2006;  91 3814-3820
• 41 Klein B E, Klein R, McBride P E et al. Cardiovascular disease, mortality, and retinal microvascular characteristics in type 1 diabetes: Wisconsin epidemiologic study of diabetic retinopathy.  Arch Intern Med. 2004;  164 1917-1924
• 42 Soedamah-Muthu S S, Chaturvedi N, Toeller M et al. Risk factors for coronary heart disease in type 1 diabetic patients in Europe: the EURODIAB Prospective Complications Study.  Diabetes Care. 2004;  27 530-537
• 43 Juutilainen A, Lehto S, Rönnemaa T et al. Similarity of the impact of type 1 and type 2 diabetes on cardiovasacular mortality in middle-aged subjects.  Diabetes Care. 2008;  31 714-719
• 44 Shankar A, Klein R, Klein B E et al. Association between glycosylated hemoglobin level and cardiovascular and all-cause mortality in type 1 diabetes.  Am J Epidemiol. 2007;  166 393-402
• 45 Monnier L, Mas E, Ginet C et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes.  JAMA. 2006;  295 1681-1687
• 46 Williams D, Erbey J, Becker D et al. Can clinical factors estimate insulin resistance in type 1 diabetes?.  Diabetes. 2000;  49 626-632
• 47 Jensen T, Borch-Johnsen K, Kofoed-Enevoldsen A et al. Coronary heart disease in young type 1 (insulin-dependent) diabetic patients with and without nephropathy: incidence and risk factors.  Diabetologia. 1987;  30 144-148
• 48 May O, Arildsen H, Damsgaard E M et al. Cardiovascular autonomic neuropathy in insulin-dependent diabetes mellitus: prevalence and estimated risk of coronary heart disease in general population.  J Inter Med. 2000;  248 483-491
• 49 Bain S C, Gill G V, Dyer P H et al. Characteristics of type 1 diabetes over 50 years duration (the Golden Years Cohort).  Diabet Med. 2003;  20 808-811