An evaluation of postprandial glucose excursions in type 2 diabetic mellitus subjects on Monotard® HM (ge) versus Humulin N® or Humulin L® insulin, each in combination with metformin

Background There is increasing evidence that postprandial hyperglycaemia is implicated in the development of macro- and microvascular diabetic complications. Thus, control of postprandial glucose levels (PPG), in addition to control of fasting blood glucose (FBG), will ensure overall glycaemic control in diabetic patients. This study evaluated the effectiveness of a current anti-diabetic regimen on PPG in patients with type 2 diabetes mellitus. Methods A total of 31 type 2 diabetic subjects on combination treatment of either Humulin N® (HN), Monotard HM (ge)® (M) or Humulin L® (HL) insulin, with metformin, participated in a controlled, prospective, one-day visit study at a tertiary referral state diabetes clinic. The objective was to evaluate the effectiveness of the combination treatment of either M (n = 11) versus HN (n = 10) or HL (n = 10) insulin, each in combination with metformin, on PPG in this study cohort. Each subject was given a standardised meal after completing baseline procedures. Prescribed insulin doses were taken the night prior to the study day and metformin doses were taken with the standardised meal on the following morning, the study day. After completion of the meal, blood glucose levels were determined every half an hour at 0, 30, 60, 90, 120 and 150 minutes, thus providing a postprandial glucose profile for each subject. The data was analysed using ANOVA. Results The study cohort was South African, predominantly of Indian origin (54.8%), with a mean age of 59.2 ± 8 years, and 71% of the cohort was female. The subjects had a mean duration of diabetes of 11.4 ± 6.6 years, with 71% (n = 22) having a positive family history. The study cohort was obese (BMI 32.3 ± 6.2kg/m2, WHR 0.9 ± 0.1). A total of 61.3% (n = 19) of the study cohort was hypertensive, while 29% (n = 9) presented with at least one cardiovascular event and 48.3% (n = 15) had high total cholesterol. On entry to the study, the mean (± SD) FBG (10.3 ± 3.7mmol/l), fructosamine (369.9 ± 78.8￭mol/l) and glycosylated haemoglobin (9 ± 2%) were elevated. Each insulin group, HN, M and HL, was statistically matched for the above-mentioned and was therefore compared. There was no statistically significant difference in the effectiveness of HN, M and HL, each in combination with metformin, on postprandial glucose levels (AUC glucose 0-150 minutes was 2100, 2212.5 and 2362.5mmol.min.l-1, per group respectively). Each insulin group presented with mean postprandial hyperglycaemia (PPH) at all time intervals (30, 60, 90, 120 and 150 minutes). Peak glucose levels were observed at 90 (16mmol/l), 90 (16.9mmol/l) and 60 minutes (17.6mmol/l) for HN, M and HL groups respectively. Since there was no statistically significant difference in PPH between and amongst the insulin groups at 60, 90 and 120 minutes, an approximation of PPG at 60 minutes would not adversely affect the determination of PPG compared to the recommended two hours. Within the HN, M and HL groups, a statistically significant difference in blood glucose levels was observed at 0 and 120 minutes (p = 0.003, 0.009 and 0.019 respectively). Groups with a higher FBG (at 0 minutes) had higher PPG (at 120 minutes), thus showing that the extent of FBG determines the degree of postprandial glycaemia. Conclusion In this study, HN, M and HL, each in combination with metformin, were not effective in controlling postprandial hyperglycaemia. HN was most effective in lowering the postprandial profile, although this was not statistically significant. The current treatment of the study cohort was also reviewed, as both FBG and PPG were not controlled. The use of a combination of short/rapid-acting insulin with a newly- formulated basal insulin is recommended, as both FBG and PPG should be treated to achieve overall glycaemic control. South African Family Practice Vol. 49 (5) 2007: pp. 1

Glycaemic control in people with diabetes following acute myocardial infarction

Diabetes is a highly prevalent disease associated with considerable cardiovascular end organ damage and mortality. Despite significant changes to the management of acute myocardial infarction over the last two decades, people with diabetes remain at risk of complications and mortality following a myocardial infarct for a multitude of reasons, including increased coronary atherosclerosis, associated coronary microvascular dysfunction, and diabetic cardiomyopathy. Dysglycaemia causes significant endothelial dysfunction and upregulation of inflammation within the vasculature and epigenetic changes mean that these deleterious effects may persist despite subsequent efforts to tighten glycaemic control. Whilst clinical guidelines advocate for the avoidance of both hyper- and hypoglcyaemia in the peri-infarct period, the evidence base is lacking, and currently there is no consensus on the benefits of glycaemic control beyond this period. Glycaemic variability contributes to the glycaemic milieu and may have prognostic importance following myocardial infarct. The use of continuous glucose monitoring means that glucose trends and parameters can now be captured and interrogated, and its use, along with newer medicines, may provide novel opportunities for intervention after myocardial infarction in people with diabetes

Thigh fat and muscle each contribute to excess cardiometabolic risk in South Asians, independent of visceral adipose tissue.

OBJECTIVE: To compare fat distribution and associations between fat depots and cardiometabolic traits in South Asians and Europeans. METHODS: Five hundred and fourteen South Asians and 669 Europeans, aged 56-86. Questionnaires, record review, blood testing, and coronary artery calcification scores provided diabetes and clinical plus subclinical coronary heart disease (CHD) diagnoses. Abdominal visceral (VAT) and subcutaneous adipose tissue, thigh subcutaneous adipose tissue (TSAT), intermuscular and intramuscular thigh fat and thigh muscle were measured by CT. RESULTS: Accounting for body size, South Asians had greater VAT and TSAT than Europeans, but less thigh muscle. Associations between depots and disease were stronger in South Asians than Europeans. In multivariable analyses in South Asians, VAT was positively associated with diabetes and CHD, while TSAT and thigh muscle were protective for diabetes, and thigh muscle for CHD. Differences in VAT and thigh muscle only partially explained the excess diabetes and CHD in South Asians versus Europeans. Insulin resistance did not account for the effects of TSAT or thigh muscle. CONCLUSIONS: Greater VAT and TSAT and lesser thigh muscle in South Asians contributed to ethnic differences in cardiometabolic disease. Effects of TSAT and thigh muscle were independent of insulin resistance

Hyperglycemia Has a Greater Impact on Left Ventricle Function in South Asians Than in Europeans

OBJECTIVE Diabetes is associated with left ventricular (LV) diastolic and systolic dysfunction. South Asians may be at particular risk of developing LV dysfunction owing to a high prevalence of diabetes. We investigated the role of diabetes and hyperglycemia in LV dysfunction in a community-based cohort of older South Asians and white Europeans. RESEARCH DESIGN AND METHODS Conventional and Doppler echocardiography was performed in 999 participants (542 Europeans and 457 South Asians aged 58–86 years) in a population-based study. Anthropometry, fasting bloods, coronary artery calcification scoring, blood pressure, and renal function were measured. RESULTS Diabetes and hyperglycemia across the spectrum of HbA1c had a greater adverse effect on LV function in South Asians than Europeans (N-terminal-probrain natriuretic peptide β ± SE 0.09 ± 0.04, P = 0.01, vs. −0.04 ± 0.05, P = 0.4, P for HbA1c/ethnicity interaction 0.02), diastolic function (E/e′ 0.69 ± 0.12, P < 0.0001, vs. 0.09 ± 0.2, P = 0.6, P for interaction 0.005), and systolic function (s′ −0.11 ± 0.06, P = 0.04, vs. 0.14 ± 0.09, P = 0.1, P for interaction 0.2). Multivariable adjustment for hypertension, microvascular disease, LV mass, coronary disease, and dyslipidemia only partially accounted for the ethnic differences. Adverse LV function in diabetic South Asians could not be accounted for by poorer glycemic control or longer diabetes duration. CONCLUSIONS Diabetes and hyperglycemia have a greater adverse effect on LV function in South Asians than Europeans, incompletely explained by adverse risk factors. South Asians may require earlier and more aggressive treatment of their cardiometabolic risk factors to reduce risks of LV dysfunction

Feasibility of Estimation of Aortic Wave Intensity Using Non-invasive Pressure Recordings in the Absence of Flow Velocity in Man

Background: Wave intensity analysis provides valuable information on ventriculo-arterial function, hemodynamics, and energy transfer in the arterial circulation. Widespread use of wave intensity analysis is limited by the need for concurrent measurement of pressure and flow waveforms. We describe a method that can estimate wave intensity patterns using only non-invasive pressure waveforms (pWIA). Methods: Radial artery pressure and left ventricular outflow tract (LVOT) flow velocity waveforms were recorded in 12 participants in the Southall and Brent Revisited (SABRE) study. Pressure waveforms were analyzed using custom-written software to derive the excess pressure (P xs ) which was scaled to peak LVOT velocity and used to calculate wave intensity. These data were compared with wave intensity calculated using the measured LVOT flow velocity waveform. In a separate study, repeat measures of pWIA were performed on 34 individuals who attended two clinic visits at an interval of ≈1 month to assess reproducibility and reliability of the method. Results: P xs waveforms were similar in shape to aortic flow velocity waveforms and the time of peak P xs and peak aortic velocity agreed closely. Wave intensity estimated using pWIA showed acceptable agreement with estimates using LVOT velocity tracings and estimates of wave intensity were similar to values reported previously in the literature. The method showed fair to good reproducibility for most parameters. Conclusion: The P xs is a surrogate of LVOT flow velocity which, when appropriately scaled, allows estimation of aortic wave intensity with acceptable reproducibility. This may enable wider application of wave intensity analysis to large studies

Cardiovascular Risk Factors from Early Life Predict Future Adult Cardiac Structural and Functional Abnormalities: A Systematic Review of the Published Literature

Background: Clinical practice evaluates cardiovascular risk based on current risk factor (RF) levels [Blood pressure (BP), body mass index (BMI) and glycaemic control] largely disregarding previous risk-factor history over the totality of the life course. RFs are related to contemporaneous echocardiographic measures of cardiac structure and function which in turn are independently related to cardiovascular morbidity and mortality in cross-sectional studies. However, the effect of lifetime or earlier RF history on future echocardiographic changes has never been systematically examined. Methods: A systematic review of the published literature identified 24 studies relating either earlier BP, BMI, glycaemic control or a combination to future cardiac structure and/or function. Results: The majority of studies showed that elevated BP and BMI in earlier life and greater cumulative burden of these factors resulted in worse cardiac structure up to 24 years later. Studies examining glycaemic control as a RF were few, but poorer glycaemic control in young adults was associated with increased future left ventricular mass. While only 5 papers related RFs to future cardiac function, all RFs were positively associated with worse future diastolic function. Conclusions: BP, BMI and glycaemic control measures in childhood, adolescence and early adulthood and subsequent longitudinal trajectories of BP and BMI are predictive of future abnormalities in cardiac structure and function. Lifetime RF history should be used to inform clinical practice. Further research is required to enable the identification of any sensitive periods in the life course to enable prevention when it is most likely to be effective

Ethnic differences in cross-sectional associations between impaired glucose regulation, identified by oral glucose tolerance test or HbA1c values, and cardiovascular disease in a cohort of European and South Asian origin

Aims We contrasted impaired glucose regulation (prediabetes) prevalence, defined according to oral glucose tolerance test or HbA1c values, and studied cross-sectional associations between prediabetes and subclinical/clinical cardiovascular disease (CVD) in a cohort of European and South Asian origin. Methods For 682 European and 520 South Asian men and women, aged 58–85 years, glycaemic status was determined by oral glucose tolerance test or HbA1c thresholds. Questionnaires, record review, coronary artery calcification scores and cerebral magnetic resonance imaging established clinical plus subclinical coronary heart and cerebrovascular disease. Results Prediabetes was more prevalent in South Asian participants when defined by HbA1c rather than by oral glucose tolerance test criteria. Accounting for age, sex, smoking, systolic blood pressure, triglycerides and waist–hip ratio, prediabetes was associated with coronary heart disease and cerebrovascular disease in European participants, most obviously when defined by HbA1c rather than by oral glucose tolerance test [odds ratios for HbA1c-defined prediabetes 1.60 (95% CI 1.07, 2.39) for coronary heart disease and 1.57 (95% CI 1.00, 2.51) for cerebrovascular disease]. By contrast, non-significant associations were present between oral glucose tolerance test-defined prediabetes only and coronary heart disease [odds ratio 1.41 (95% CI 0.84, 2.36)] and HbA1c-defined prediabetes only and cerebrovascular disease [odds ratio 1.39 (95% CI 0.69, 2.78)] in South Asian participants. Prediabetes defined by HbA1c or oral glucose tolerance test criteria was associated with cardiovascular disease (defined as coronary heart and/or cerebrovascular disease) in Europeans [odds ratio 1.95 (95% CI 1.31, 2.91) for HbA1c prediabetes criteria] but not in South Asian participants [odds ratio 1.00 (95% CI 0.62, 2.66); ethnicity interaction P = 0.04]. Conclusions Prediabetes appeared to be less associated with cardiovascular disease in the South Asian than in the European group. These findings have implications for screening, and early cardiovascular prevention strategies in South Asian populations

Adverse effect of diabetes and hyperglycaemia on arterial stiffness in Europeans, South Asians, and African Caribbeans in the SABRE study

OBJECTIVES: Ethnic minority groups in the UK experience marked differences in cardiovascular disease risk. We investigated differences in arterial central haemodynamics, stiffness, and load in a tri-ethnic population-based cohort. METHODS: A total of 1312 participants (70 ± 6 years) underwent echocardiography and measurement of brachial and central blood pressure to assess central arterial haemodynamics including central pulse pressure (cPP), arterial stiffness [cPP/stroke volume (SV)], systemic vascular resistance (SVR), and load (Ea). RESULTS: Brachial and central SBPs were similar in all ethnic groups. Compared with Europeans, cPP, cPP/SV, and Ea were higher in South Asians. In contrast, cPP/SV was lower in African Caribbeans despite higher mean arterial pressure, higher SVR, and higher diabetes prevalence. cPP/SV and Ea remained significantly higher in South Asians and significantly lower in African Caribbeans after multivariate adjustment. Diabetes and higher HbA1c were more strongly associated with higher cPP/SV in South Asians than in Europeans (Pinteraction = 0.045 and 0.005, respectively); higher HbA1c was also more strongly associated with increased Ea in South Asians than Europeans (Pinteraction = 0.01). There was no evidence of an interaction between glycaemia and cPP/SV in African Caribbeans. CONCLUSIONS: Compared with Europeans, South Asians have unfavorable arterial function. Diabetes and hyperglycaemia have a more deleterious effect on cPP/SV and Ea in South Asians. In contrast, African Caribbeans have more favourable arterial function than Europeans and South Asians. These differences may contribute to the differential ethnic rates of cardiovascular disease