Biphasic insulin aspart 30/70 (BIAsp 30) in the treatment of type 1 and type 2 diabetes

The pharmacological advantages of the rapid-acting analog, insulin aspart, over human insulin have contributed to the widespread prescription of the premix, biphasic insulin aspart 30/70 (BIAsp 30), in type 1 (T1DM) and type 2 diabetes (T2DM). This article reviews the available literature on the pharmacology, efficacy and safety of BIAsp 30 in T1DM and T2DM from an online search of the PubMed database. Following injection, BIAsp 30 reaches higher plasma insulin levels more quickly than human premix or basal insulin, giving effective reduction of postprandial hyperglycemia. In T1DM patients, randomized controlled trials (RCTs) have shown that HbA1c reduction is similar, but postprandial glycemic control is better, with BIAsp 30 than with human insulin regimens. In T2DM patients, lowering of HbA1c and postprandial hyperglycemia with BIAsp 30 compare favorably with optimized oral antidiabetes drug treatment, insulin glargine, and, in obese patients, human premix. An increase in minor hypoglycemia with BIAsp 30 relative to basal insulin has been reported in T2DM patients, but major and nocturnal hypoglycemia rates are generally low. Findings from RCTs in T2DM patients are supported by large observational studies. In summary, BIAsp 30 once to three times daily represents a simple and effective tool for the modern management of diabetes

Type 1 diabetes and cardiovascular disease

The presence of cardiovascular disease (CVD) in Type 1 diabetes largely impairs life expectancy. Hyperglycemia leading to an increase in oxidative stress is considered to be the key pathophysiological factor of both micro- and macrovascular complications. In Type 1 diabetes, the presence of coronary calcifications is also related to coronary artery disease. Cardiac autonomic neuropathy, which significantly impairs myocardial function and blood flow, also enhances cardiac abnormalities. Also hypoglycemic episodes are considered to adversely influence cardiac performance. Intensive insulin therapy has been demonstrated to reduce the occurrence and progression of both micro- and macrovascular complications. This has been evidenced by the Diabetes Control and Complications Trial (DCCT) / Epidemiology of Diabetes Interventions and Complications (EDIC) study. The concept of a metabolic memory emerged based on the results of the study, which established that intensified insulin therapy is the standard of treatment of Type 1 diabetes. Future therapies may also include glucagon-like peptide (GLP)-based treatment therapies. Pilot studies with GLP-1-analogues have been shown to reduce insulin requirements

Flow-mediated-paradoxical vasoconstriction is independently associated with asymptomatic myocardial ischemia and coronary artery disease in type 2 diabetic patients.

International audienceBACKGROUND: To investigate whether flow-mediated dilation (FMD) impairment, which precedes overt atherosclerosis, is associated with silent myocardial ischemia (SMI) and asymptomatic coronary artery disease (CAD) in type 2 diabetes. METHODS: Forearm FMD was measured by ultrasonography in 25 healthy control, 30 non-diabetic overweight or obese patients and 118 asymptomatic type 2 diabetic patients with a high cardiovascular risk profile. SMI (abnormal stress myocardial scintiscan and/or stress dobutamine echocardiogram) and CAD (coronary angiography in the patients with SMI) were assessed in the diabetic cohort. RESULTS: FMD was lower in diabetic patients (median 0.61% (upper limits of first and third quartiles -1.22;3.2)) than in healthy controls (3.95% (1.43;5.25), p < 0.01) and overweight/obese patients (4.25% (1.74;5.56), p < 0.01). SMI was present in 60 diabetic patients, including 21 subjects with CAD. FMD was lower in patients with SMI than in those without (0.12% (-2.3;1.58) vs 1.64% (0;3.69), p < 0.01), with a higher prevalence of paradoxical vasoconstriction (50.0% vs 29.3%, p < 0.05). FMD was also lower in patients with than without CAD (-1.22% (-2.5;1) vs 1.13% (-0.4;3.28), p < 0.01; paradoxical vasoconstriction 61.9% vs 34.4%, p < 0.05). Logistic regression analyses considering the parameters predicting SMI or CAD in univariate analyses with a p value <0.10 showed that paradoxical vasoconstriction (odds ratio 2.7 [95% confidence interval 1.2-5.9], p < 0.05) and nephropathy (OR 2.6 [1.2-5.7], p < 0.05) were independently associated with SMI; and only paradoxical vasoconstriction (OR 3.1 [1.2-8.2], p < 0.05) with CAD. The negative predictive value of paradoxical vasoconstriction to detect CAD was 88.7%. CONCLUSIONS: In diabetic patients, FMD was independently associated with SMI and asymptomatic CAD.Trial registration: Trial registration number NCT00685984

Influence of blood glucose on heart rate and cardiac autonomic function. The DESIR study.

International audienceOBJECTIVES:   To evaluate in a general population, the relationships between dysglycaemia, insulin resistance and metabolic variables, and heart rate, heart rate recovery and heart rate variability. METHODS:   Four hundred and forty-seven participants in the Data from an Epidemiological Study on the Insulin Resistance syndrome (DESIR) study were classified according to glycaemic status over the preceding 9 years. All were free of self-reported cardiac antecedents and were not taking drugs which alter heart rate. During five consecutive periods: rest, deep breathing, recovery, rest and lying to standing, heart rate and heart rate varability were evaluated and compared by ANCOVA and trend tests across glycaemic classes. Spearman correlation coefficients quantified the relations between cardio-metabolic risk factors, heart rate and heart rate varability. RESULTS:   Heart rate differed between glycaemic groups, except during deep breathing. Between rest and deep-breathing periods, patients with diabetes had a lower increase in heart rate than others (P(trend) < 0.01); between deep breathing and recovery, the heart rate of patients with diabetes continued to increase, for others, heart rate decreased (P(trend) < 0.009). Heart rate was correlated with capillary glucose and triglycerides during the five test periods. Heart rate variability differed according to glycaemic status, especially during the recovery period. After age, sex and BMI adjustment, heart rate variability was correlated with triglycerides at two test periods. Change in heart rate between recovery and deep breathing was negatively correlated with heart rate variability at rest, (r=-0.113, P < 0.05): lower resting heart rate variability was associated with heart rate acceleration. CONCLUSIONS:   Heart rate, but not heart rate variability, was associated with glycaemic status and capillary glucose. After deep breathing, heart rate recovery was altered in patients with known diabetes and was associated with reduced heart rate variability. Being overweight was a major correlate of heart rate variability

Atherosclerotic cardiovascular disease risk stratification and management in type 2 diabetes: review of recent evidence-based guidelines

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality and morbidity in individuals with type 2 diabetes mellitus (T2DM). Accordingly, several scientific societies have released clinical practice guidelines to assist health professionals in ASCVD risk management in patients with T2DM. However, some recommendations differ from each other, contributing to uncertainty about the optimal clinical management of patients with T2DM and established ASCVD or at high risk for ASCVD. Thus, the purpose of this paper is to discuss recent evidence-based guidelines on ASCVD risk stratification and prevention in patients with T2DM, in terms of disparities and similarities. To close the gap between different guidelines, a multidisciplinary approach involving general practitioners, endocrinologists, and cardiologists may enhance the coordination of diagnosis, therapy, and long-term follow-up of ASCVD in patients with T2DM

A REAPPRAISAL OF LOWER TO MIDDLE PALAEOLITHIC BONE RETOUCHERS FROM SOUTHEASTERN FRANCE (MIS 11 TO 3)

International audienceIn southeastern France, many Final Acheulean/Early Middle Palaeolithic and Middle Palaeolithic assemblages have yielded bone retouchers. The oldest are dated to the Middle Pleistocene: from MIS 11 at Terra Amata; MIS 9 at Orgnac 3; and MIS 6-7 at Payre F, Sainte-Anne I and Le Lazaret. However, this early evidence of bone tool use only concerns a few dozen pieces among thousands of faunal and lithic remains. These re-touchers indicate behavioural changes from MIS 11-9 onwards in southeastern France, associated with a mosaic of technological and subsistence changes that became more common during the Middle Palaeolithic. The frequency of these bone artefacts increases during MIS 7, becoming much more numerous after MIS 5, sometimes totaling more than a hundred items at one site, such as Saint-Marcel Cave. Bone retoucher frequency is still highly variable throughout the Middle Palaeolithic and seems to be determined by the type of occupation and activities rather than the associated lithic technologies. This broad, regional comparative analysis contributes to a better understanding of the technical behaviour developed by Neanderthals, as well as their Middle Pleistocene ancestors, and their ability to recover and use bones

Predictive value of cardiac autonomic neuropathy in diabetic patients with or without silent myocardial ischemia

WSTĘP. Celem badania było ustalenie wartości predykcyjnej niemego niedokrwienia mięśnia sercowego (SMI, silent myocardial ischemia) i neuropatii układu autonomicznego serca (CAN, cardiac autonomic neuropathy) u chorych na cukrzycę bez objawów choroby niedokrwiennej serca. MATERIAŁ I METODY. Do badania włączono 120 chorych na cukrzycę, którzy nie przebyli zawału serca i u których wcześniej nie rozpoznano dławicy piersiowej, z prawidłowym zapisem elektrokardiograficznym (EKG) z 12 odprowadzeń oraz z co najmniej dwoma dodatkowymi czynnikami ryzyka. Nieme niedokrwienie mięśnia sercowego rozpoznawano na podstawie elektrokardiograficznej próby wysiłkowej, scyntygrafii mięśnia sercowego z zastosowaniem talu201 po obciążeniu dipirydamolem i 48-godzinnego monitorowania EKG. Neuropatię układu autonomicznego serca wykrywano za pomocą standaryzowanych badań oceniających zmienność rytmu serca. Dokładne dane z trwającej 3-7 lat (średnio 4,5 roku) obserwacji uzyskano od 107 osób. WYNIKI. U 33 chorych (30,7%) stwierdzono SMI. U 33 spośród 75 zbadanych osób (38,9%) wykryto CAN, a u 11 z nich doszło do poważnych incydentów sercowych. Spośród tych 75 chorych poważne incydenty sercowe występowały podobnie często w grupach SMI+ i SMI- (odpowiednio 6 incydentów u 25 osób vs. 5 u 50 osób), natomiast były znacznie częstsze w grupie CAN+ niż CAN- (odpowiednio 8 u 33 vs. 3 u 42 osób, p = 0,04), z ryzykiem względnym wynoszącym 4,16 (95% CI 1,01-17,19). Największą częstość analizowanych incydentów obserwowano u chorych z SMI i CAN (u 5 z 10 osób). Po skorygowaniu względem SMI stwierdzono istotną zależność między CAN a poważnymi incydentami sercowymi (p = 0,04). WNIOSKI. W przypadku chorych na cukrzycę bez objawów choroby niedokrwiennej serca, CAN wydaje się lepszym parametrem zwiastującym możliwość wystąpienia poważnych incydentów wieńcowych niż SMI. Ryzyko związane z wystąpieniem CAN jest niezależne od występowania SMI i jest najwyższe, gdy CAN i SMI obserwuje się u tego samego pacjenta.INTRODUCTION. The aim of this study was to determine the predictive value of silent myocardial ischemia (SMI) and cardiac autonomic neuropathy (CAN) in asymptomatic diabetic patients. MATERIAL AND METHODS. We recruited 120 diabetic patients with no history of myocardial infarction or angina, a normal 12-lead electrocardiogram (ECG), and two or more additional risk factors. SMI assessment was carried out by means of an ECG stress test, a thallium-201 myocardial scintigraphy with dipyridamole, and 48-h ECG monitoring. CAN was searched for by standardized tests evaluating heart rate variations. Accurate follow-up information for 3&#8211;7 years (mean 4.5) was obtained in 107 patients. RESULTS. There was evidence of SMI in 33 patients (30.7%). CAN was detected in 33 of the 75 patients (38.9%) who were tested, and a major cardiac event occurred in 11 of them. Among these 75 patients, the proportion of major cardiac events in the SMI+ patients was not significantly higher than that in the SMI&#8211; patients (6 of 25 vs. 5 of 50 patients), whereas it was significantly higher in the CAN+ patients than in the CAN&#8211; patients (8 of 33 vs. 3 of 42 patients; P = 0.04), with a relative risk of 4.16 (95% CI 1.01&#8211;17.19) and was the highest in the patients with both SMI and CAN (5 of 10 patients). After adjusting for SMI, there was a significant association between CAN and major cardiac events (P = 0.04). CONCLUSIONS. In asymptomatic diabetic patients, CAN appears to be a better predictor of major cardiac events than SMI. The risk linked to CAN appears to be independent of SMI and is the highest when CAN is associated with SMI