Subscribe to RSS
DOI: 10.1055/s-0028-1112136
© Georg Thieme Verlag KG Stuttgart · New York
Optimized Postprandial Glucose Control is Associated with Improved Cardiac/Vascular Function – Comparison of Three Insulin Regimens in Well-controlled Type 2 Diabetes
Publication History
received 24.09.2008
accepted 24.11.2008
Publication Date:
12 February 2009 (online)
![](https://www.thieme-connect.de/media/hmr/200902/lookinside/thumbnails/10.1055-s-0028-1112136-1.jpg)
Abstract
In people with type 2 diabetes (T2DM), hyperglycemia has a negative impact on cardiac function and cardiovascular risk. Beneficial effects of improved postprandial glycemic control have been shown for cardiovascular risk only. To demonstrate these beneficial effects on myocardial function, we investigated well-controlled T2DM patients on three insulin regimens with different impact on postprandial glucose control. For 24 months, 61 T2DM participants in a randomized study had either conventional therapy (CT) with human premixed insulin b.d. (n=20), intensified therapy (ICT) with Lispro at meals and NPH at bedtime (n=24), or supplementary therapy (SIT) with human regular insulin at meals (n=17). Metabolism and cardiovascular function were assessed before and 2 hours after a standardized carbohydrate breakfast (48 g) using tissue Doppler to measure diastolic myocardial function (E′). Age, BMI, dose of insulin, cardiovascular disease, and medication were comparable between the groups. Hb1Ac was comparable with CT, ICT, and SIT (6.6±0.6, 6.2±0.6, and 6.4±0.7%) and so was fasting glucose. Post-meal glucose increment was 60±45 mg/dl with CT, but 15±52 and 8±58 mg/dl with ICT and SIT (p<0.006). E′ was significantly lower (p<0.03) with CT (6.8±1.0 cm/s) vs. ICT (7.7±1.6) and SIT (7.8±1.2 cm/s), and correlated with post-meal glucose (r=−0.2644, p<0.046). Intima-media thickness and arterial stiffness parameters were higher in CT (p<0.04). In T2DM patients, the long-term insulin regimens CT, ICT, and SIT achieved overall good metabolic control with significant differences, however, in postprandial glucose increments. The regimens achieving better post-meal glucose control were associated with better myocardial/vascular function.
Key words
postprandial hyperglycemia - diastolic function - tissue Doppler - type 2 diabetes - insulin therapy
References
- 1 Bartnik M, Malmberg K, Rydén L. Diabetes and the heart: compromised myocardial function – a common challenge. Eur Heart J Suppl. 2003; 5 ((Suppl. B)) B33-B41
- 2 Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999; 22 233-240
- 3 Colette C, Monnier L. Acute glucose fluctuations and chronic sustained hyperglycemia as risk factors for cardiovascular diseases in patients with type 2 diabetes. Horm Metab Res. 2007; 39 683-686
- 4 Hanefeld M, Ceriello A, Schwarz PE, Bornstein SR. The metabolic syndrome – a postprandial disease?. Horm Metab Res. 2006; 38 435-436
- 5 Schwarz PE, Schwarz J, Bornstein SR, Schulze J. Diabetes prevention – from physiology to implementation. Horm Metab Res. 2006; 38 460-464
- 6 Ceriello A, Colagiuri S, Gerich J, Tuomilehto J. Guideline for management of postmeal glucose. Nutr Metab Cardiovasc Dis. 2008; 18 17-33
- 7 Chiasson JL. Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial. Endocr Pract. 2006; 12 ((Suppl. 1)) 25-30
- 8 Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, Kojima Y, Furuyoshi N, Shichiri M. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995; 28 103-117
- 9 Celentano A, Vaccaro O, Tammaro P, Galderisi M, Crivaro M, Oliviero M, Imperatore G, Palmieri V, Iovino V. Early abnormalities of cardiac function in non-insulin-dependent diabetes mellitus and impaired glucose tolerance. Am J Cardiol. 1995; 76 1173-1176
- 10 Fang ZY, Schull-Maede R, Downey M, Prins J, Marwick TH. Determin-ants of subclinical diabetic heart disease. Diabetologia. 2005; 48 394-402
- 11 Mariß K, Guggenberger G, Hepp KD, Hollweck R, Lüddeke HJ, Renner R, Schumm-Draeger PM. Intensified conventional insulin therapy (ICT) versus conventional therapy (CT) in patients with type 2 diabetes (n=150): A 1-year open, randomized therapy study. IDF 2003. Diabetes Metab. 2003; 29 4S7-4S428
- 12 von Bibra H, Thrainsdottir IS, Hansen A, Dounis V, Malmberg K, Rydén L. Tissue Doppler imaging for detection and quantitation of myocardial dysfunction in patients with type 2 diabetes: A methodological study. Diabetes Vasc Dis Res. 2005; 2 483-487
- 13 Inelli P, Sanchez R, Marra F, Esposito R, Galderisi M. The impact of aging on left ventricular longitudinal function in healthy subjects: a pulsed tissue Doppler study. Eur J Echocardiogr. 2008; 9 241-249
- 14 Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997; 30 1527-1533
- 15 Avgeropoulou C, Illmann A, Schumm-Draeger P-M, Kallikazaros J, von Bibra H. Assessment of arterio-ventricular coupling by tissue Doppler and wave intensity in type 2 diabetes. Br J Diabetes Vasc Dis. 2006; 6 271-278
- 16 Sugawara M, Niki K, Furuhata H, Ohnishi S, Suzuki S. Relationship between the pressure and diameter of the carotid artery in humans. Heart Vessels. 2000; 15 49-51
- 17 Henry RM, Kostense PJ, Spjikerman AM, Dekker JM, Nijpels G, Heine RJ, Kamp O, Westerhof N, Bouter LM, Stehouwer CDL. Arterial stiffness increases with deteriorating glucose tolerance status: the Hoorn Study. Circulation. 2003; 107 2089-2095
- 18 Simon A, Gariepy J, Chironi G Megnien JL, Levenson J. Intima-media thickness: a new tool for diagnoses and treatment of cardiovascular risk. J Hypertens. 2002; 20 159-169
- 19 Ceriello A, Quagliaro L, Piconi L, Assaloni R, Da Ros R, Maier A, Esposito K, Giugliano D. Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes. 2004; 53 701-710
- 20 Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress by acute fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006; 295 1681-1687
- 21 Pistrosch F, Koehler C, WildbrettJ, HanefeldM. Relationship between diurnal glucose levels and HbA1c in type 2 diabetes. Horm Metab Res. 2006; 38 455-459
- 22 Yu CM, Sanderson JE, Marwick TH, Oh JK. Tissue Doppler Imaging. A new prognosticator for cardiovascular disease. J Am Coll Cardiol. 2007; 49 1903-1914
- 23 Hansen A, Johansson BL, Warren C, von Bibra H. C-peptide exerts beneficial effects on myocardial blood flow and function in patients with type 1 diabetes. Diabetes. 2002; 51 3077-3082
- 24 Dounis V, Siegmund T, Jensen J, Hansen A, Schumm-Draeger PM, von Bibra H. Global myocardial perfusion and diastolic function are impaired to a similar extent in patients with type 2 diabetes mellitus and in patients with coronary artery disease- evaluation by contrast echocardiography and pulsed tissue Doppler. Diabetologia. 2006; 49 2729-2740
- 25 Miyashita T, Okano Y, Takaki H, Satoh T, Kobayashi Y, Goto Y. Relation between exercise capacity and left ventricular systolic versus diastolic function during exercise in patients after myocardial infarction. Coronary Artery Disease. 2001; 12 217-225
- 26 Bella JN, Palmieri V, Roman MJ, Liu JE, Welty TK, Lee ET, Fabsitz RR, Howard BV, Devereux RB. Mitral ratio of peak early to late diastolic filling velocity as a predictor of mortality in middle-aged and elderly adults. The Strong Heart Study. Circulation. 2002; 105 1928-1933
- 27 Vinereanu D, Nicolaides E, Boden L, Payne N, Jones CJ, Fraser A. Conduit arterial stiffness is associated with impaired left ventricular function. Heart. 2003; 89 449-450
- 28 Irribarren C, Karter AJ, Go AS, Ferrara A, Liu JY, Sidney S, Selby JV. Glycemic control and heart failure among adult patients with diabetes. Circulation. 2001; 103 2668-2673
- 29 von Bibra H, Hansen A, Dounis V, Bystedt T, Malmberg K, Rydén L. Insulin based improved metabolic control augments myocardial diastolic function and perfusion in patients with type 2 diabetes mellitus. Heart. 2004; 90 1483-1484
- 30 von Bibra H, Siegmund T, Hansen A, Jensen J, Schumm-Draeger PM. Improved myocardial function by improved metabolic control in patients with type 2 diabetes mellitus. Dtsch Med Wochenschr. 2007; 132 729-734
- 31 Brownlee M. The pathophysiology of diabetic complications: a unifying mechanism. Diabetes. 2005; 54 1615-1625
- 32 Diamant M, Lamb HJ, Groeneveld Y, Endert EL, Smit JW, Bax JJ Romijn JA, de Roos A, Radder JK. Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus. J Am Coll Cardiol. 2003; 42 328-335
- 33 Kim J, Montagnani M, Kon Koh K, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction – molecular and pathophysiological mechanisms. Circulation. 2006; 113 1888-1904
- 34 Bellin C, de Wiza DH, Wiernsperger NF, Rösen P. Generation of reactive oxygen species by endothelial and smooth muscle cells: Influence of hyperglycemia and metformin. Horm Metab Res. 2006; 38 732-739
- 35 Major-Pedersen A, Ihlemann N, Hermann TS, Christiansen B, Kveiborg B, Domingueez H, Nielsen D, Rak-Madsen C, Svendsen OL, Kober L, Torp-Pedersen C. Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: is stimulation of first phase insulin secretion beneficial for the endothelial function?. Horm Metab Res. 2008; 40 607-613
- 36 Schalkwijk CG, Brouwers O, Stehouwer CDA. Modulation of insulin action by advanced glycation endproducts: A new player in the field. Horm Metab Res. 2008; 40 614-619
- 37 von Bibra H, Ceriello A, Siegmund T, Schumm-Draeger PM. Postprandial hyperglycemia induced oxidative stress generation is associated with cardiovascular dysfunction in patients with type 2 diabetes – assessed by pulsed tissue Doppler and Wave-Intensity. Diabetologia. 2008; 51 ((Suppl. 1)) 30ab
Correspondence
Prof. H. von Bibra
Klinikum Bogenhausen, Städt. Klinikum München GmbH
Englschalkingerstr. 77
81925 München
Germany
Phone: +49/89/9270 21 18
Fax: +49/89/9270 21 16
Email: von-Bibra@extern.lrz-muenchen.de