Optimized Postprandial Glucose Control is Associated with Improved Cardiac/Vascular Function – Comparison of Three Insulin Regimens in Well-controlled Type 2 Diabetes

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.

Impact of glycemic control with sitagliptin on the 2-year progression of arterial stiffness: a sub-analysis of the PROLOGUE study

“…On the other hand, controversial results have been reported about the effect of glycemic control on the arterial stiffness [6, 21]. In the overall subject population in this study, the HbA1c value decreased from 6.9 to 6.7%, however, this small reduction of the HbA1c value was not associated with any significant reduction of the arterial stiffness.…”

“…Some studies have reported that the treatment of diabetes is associated with a reduction of the arterial stiffness [6–9]. Recently, new orally administered dipeptidyl peptidase 4 (DPP-4) inhibitors have become available for the treatment of diabetes [10].…”

Clinical Update: Cardiovascular Disease in Diabetes Mellitus

“…350 Therefore, HbA 1c is only one indicator of risk for microvascular complications of diabetes, and whether HbA 1c is a valid surrogate endpoint for macrovascular disease risk remains uncertain. Investigation into new risk markers that account for factors not captured by HbA 1c that may impact risk of complications 59,351,352 and risk prediction models including these new putative factors is needed. 353 …”

Control of Postprandial Glucose Levels with Insulin in Type 2 Diabetes

“…23 Patients with well-controlled T2DM received either conventional therapy (premixed RHI twice daily; n = 20), intensifi ed therapy (prandial fast-acting insulin analog and NPH insulin at bedtime; n = 24), or supplementary therapy (additional RHI at meals; n = 17). All 3 regimens achieved overall good glycemic control, but PPG excursions were signifi cantly lower in patients receiving intensifi ed or supplementary therapy.…”