Assessment of microvascular endothelial function in type 1 diabetes using laser speckle contrast imaging.

OBJECTIVE: To test whether laser speckle contrast imaging (LSCI) coupled with physiological post-occlusive reactive hyperemia (PORH) and pharmacological iontophoresis of acetylcholine (ACh) as local vasodilator stimuli could distinguish between cutaneous microvascular responses of Type 1 Diabetes (T1DM)'s patients with endothelial dysfunction and that of healthy controls. METHODS: Patients with T1DM aged ≥12years completed a clinical-epidemiological questionnaire. Data detailing patients' such as daily insulin dose, duration of diabetes, and use of pharmaceuticals such as antihypertensive drugs and statins that could interfere with endothelial function were obtained. Vascular reactivity was assessed in the forearm by LSCI and PORH at baseline and during iontophoresis of ACh using increasing anodic currents of 30, 60, 90, 120, 150 and 180µA in 10second intervals. RESULTS: This study included 50 patients with T1DM and 30 control subjects. The mean resting flux did not differ between patients and control subjects. T1DM patients exhibited endothelial dysfunction upon challenge with physiological or pharmacological stimuli. The microvascular response to both ACh and PORH (i.e., maximum response at peak and amplitude) were significantly reduced in patients with diabetes compared with control subjects (p<0.001). CONCLUSION: We demonstrated that endothelium-dependent skin microvascular vasodilator responses are significantly impaired in patients with T1DM compared to healthy subjects investigated using LSCI coupled with ACh iontophoresis and PORH. Additionally, we find that LSCI is a promising methodology for studying physiological vascular reactivity in T1DM.

Integrating Biomarkers and Imaging for Cardiovascular Disease Risk Assessment in Diabetes.

Cardiovascular disease (CVD) risk assessment has changed substantially in recent years. While older guidelines considered diabetes a coronary disease risk equivalent, more recent guidelines recommend risk stratification on the basis of global risk scoring to target intensity of therapy. While patients with diabetes as a whole are at greater risk for CVD events, these patients may also benefit from risk stratification based on circulating biomarkers like high-sensitivity C-reactive protein, high-sensitivity cardiac troponin T, and N-terminal pro-B-type natriuretic peptide, as well as newer imaging modalities (coronary artery calcium, carotid intima-media thickness, and myocardial perfusion imaging). The addition of these CVD risk assessment modalities could play an important role for deciding how aggressive a physician should be with pharmacological therapy. Here, we discuss many of the current recommendations of CVD risk assessment in patients with diabetes including newer modalities for CVD risk assessment.

Clinical importance of assessment of type 2 diabetes mellitus with visceral obesity. A Japanese perspective.

Type 2 diabetes mellitus (T2DM) is a complex heterogeneous group of metabolic disorders including hyperglycemia and impaired insulin action and/or insulin secretion. Obesity T2DM has become a serious problem in Japan as in Western countries, with over-eating and physical inactivity. Obese Asians have mild degree of adiposity, compared with Western subjects. Unlike total body fat, body fat distribution, especially excess accumulation of visceral fat, correlates with various diabetogenic, atherogenic, prothrombotic and proinflammatory metabolic abnormalities, which increase the risk of atherosclerotic cardiovascular disease (ACVD). Obese patients with T2DM have poor glycemic control with disordered eating behaviors, and complications of hypertension and dyslipidemia, leading to ACVD. The major therapies in obese T2DM, hyperinsulinemia and low insulin sensitivity, available for weight loss, especially visceral fat reduction, include caloric restriction, physical activity and behavior modification. On the other hand, the major therapies in non-obese T2DM with insufficient insulin secretion, are insulin-secretory agents and injectable insulin. For clinically meaningful prevention/reduction in the rate of future ACVD in T2DM, it may be important to stratify T2DM subjects into those with and without visceral obesity and design specific management protocols for each group.

The assessment of glycemic variability and its impact on diabetes-related complications: an overview.

There is a growing body of evidence that the sole use of hemoglobin A1c is insufficient to adequately reflect the metabolic situation of patients with diabetes mellitus. The risk of developing diabetes-related complications apparently not only depends on the long-term stability of glucose values, but also on the presence or occurrence of short-term glycemic peaks and nadirs lasting for minutes or hours during a day. This leads to the phenomenon of glycemic variability. This article reviews the existing evidence for the clinical relevance of short-term glucose variations and the currently available different means of measuring glycemic variability.

Estimated glucose disposal rate in assessment of the metabolic syndrome and microvascular complications in patients with type 1 diabetes.

OBJECTIVE: The objective of the study was to quantify insulin resistance in type 1 diabetes patients by estimated glucose disposal rate (eGDR), according to the presence or absence of the metabolic syndrome, and its relationship with chronic complications. DESIGN: This was a cross-sectional study in 91 patients with type 1 immune-mediated diabetes managed at an outpatient endocrinology clinic. All participants were Caucasians aged 18 yr or older with type 1 diabetes duration of more than 6 months who had completed the study protocol. RESULTS: Twenty-nine patients met metabolic syndrome criteria, yielding a prevalence of 31.9%. Although no differences in insulin requirements were found between diabetic patients with and without metabolic syndrome, lower eGDR levels, indicating greater insulin resistance, were observed in metabolic syndrome patients compared with those without (6.19 +/- 1.5 mg/kg(-1) x min(-1) vs. 9.93 +/- 1.6 mg/kg(-1) x min(-1)) (P < 0.001). An eGDR level less than 8.77 mg/kg(-1) x min(-1) showed 100% sensitivity and 85.2% specificity for metabolic syndrome diagnosis. All patients with diabetes complications had eGDR values below 8.16 mg/kg(-1) x min(-1). eGDR level was significantly lower in patients with diabetic retinopathy (5.97 +/- 1.2 mg/kg(-1) x min(-1)), diabetic neuropathy (5.06 +/- 0.4 mg/kg(-1) x min(-1)), or diabetic nephropathy (5.79 +/- 1.5 mg/kg(-1) x min(-1)) compared with those without (9.38 +/- 2.0 mg/kg(-1) x min(-1), P < 0.001; 9.26 +/- 2.0 mg/kg(-1) x min(-1), P < 0.001; and 9.19 +/- 2.2 mg/kg(-1) x min(-1), P < 0.001). CONCLUSIONS: Insulin resistance is common in type 1 diabetes patients and is associated with microvascular complications. eGDR, as an insulin resistance marker, provides more useful information than other classical variables such as insulin requirements.

An association between ethnicity and cardiovascular outcomes for people with Type 2 diabetes in New Zealand.

AIMS: To investigate the association between ethnicity and risk of first cardiovascular (CV) event for people with Type 2 diabetes in New Zealand. METHODS: A prospective cohort study using routinely collected data from a national primary health care diabetes annual review programme linked to national hospital admission and mortality data. Ethnicity was recorded as European, Maori, Pacific, Indo-Asian, East-Asian or Other. A Cox proportional hazards model was used to investigate factors associated with first CV event. Data was collected from 48,444 patients with Type 2 diabetes, with first data collected between 1 January 2000 and 20 December 2005, no previous cardiovascular event at entry and with complete measurements. Risk factors included ethnicity, gender, socio-economic status, body mass index, smoking, age at diagnosis, duration of diabetes, systolic blood pressure, serum lipids, glycated haemoglobin and urine albumin : creatinine ratio. The main outcome measures were time to first fatal or non-fatal CV event. RESULTS: Median follow-up was 2.4 years. Using combined European and Other ethnicities as a reference, hazard ratios for first CV event were 1.30 for Maori (95% confidence interval 1.19-1.41), 1.04 for Pacific (0.95-1.13), 1.06 for Indo-Asian (0.91-1.24) and 0.73 for East-Asian (0.62-0.85) after controlling for all other risk factors. CONCLUSIONS: Ethnicity was independently associated with time to first CV event in people with Type 2 diabetes. Maori were at 30% higher risk of first CV event and East-Asian 27% lower risk compared with European/Other, with no significant difference in risk for Pacific and Indo-Asian peoples.

Assessment of oxidative stress and endothelial dysfunction in Asian Indians with type 2 diabetes mellitus with and without macroangiopathy.

BACKGROUND: Enhanced oxidative stress coupled with increased expression of adhesion molecules (e.g. VCAM-1, ICAM-1) and decreased nitric oxide (NO) levels are implicated in development of atheromatous vascular lesion in diabetes. The present study addresses the correlation between oxidative stress, vascular cell adhesion molecules-1 (VCAM-1), NO end products and macroangiopathic complications in type 2 diabetes mellitus (DM). DESIGN AND METHODS: The study population consisted of three groups (i) diabetic patients with macroangiopathy (Group I); (ii) diabetic patients without macroangiopathy (Group II) and (iii) healthy controls (Group III) (n = 30, each group). RESULTS: Serum malondialdehyde(MDA) concentration was significantly higher in diabetic patients as compared to controls. Group I had significantly higher malondialdehyde level as compared to Group II (P < 0.05) (5.12 +/- 1.83 micromol/l vs. 4.22 +/- 1.03 micromol/l), suggesting higher oxidative stress in patients with macroangiopathy. Significant reduction in NO end products was observed in diabetic patients compared to controls. Levels of serum NO end products levels were further reduced in patients with macroangiopathy compared to those without macroangiopathy. Group I (971.67 +/- 230.13 ng/ml) and Group II (823.55 +/- 197.74 ng/ml) had significantly higher level of sVCAM-1 compared to healthy controls (541.14 +/- 118.25 ng/ml) (P < 0.001). Also, patients with macroangiopathy had significantly higher levels of sVCAM-1 compared to those without macroangiopathy (P < 0.05). Multiple regression analysis indicated that post-prandial blood glucose, GSH and MDA were independent predictors of sVCAM-1 level (R = 0.690, P = 0.000). CONCLUSION: It can be concluded from the present study that an enhanced oxidative stress coupled with endothelial dysfunction as indicated by reduced activity of NO pathway and enhanced expression of sVCAM-1 play an important intermediary role in the pathogenesis of macrovascular complications in type 2 DM.

Erythrocyte oxidative stress in clinical management of diabetes and its cardiovascular complications.

Diabetes mellitus is a chronic disease in its own right and is also regarded as a cardiovascular risk factor as well as a cardiovascular disease, due to its ability to progress to a stage of cardiovascular co-morbidity. The pathophysiology of cardiovascular complications in diabetes is reported to involve hyperglycaemia-induced oxidative stress. The erythrocyte has an array of endogenous antioxidants involved in quenching oxidant production and the exponential chain reactions in diabetes. When the erythrocyte is oxidatively stressed, as demonstrated by depleted reduced glutathione and/or increased malondialdehyde in its cell membrane, the risk of diabetes progression and its cardiovascular sequelae, including atherosclerosis and coronary artery disease, is increased. Virtually all studies that determined erythrocyte malondialdehyde and glutathione in diabetes show consistently increased and reduced levels, respectively. Furthermore, cardiovascular complications of diabetes are reported to commence at the prediabetes stage. Current coronary artery disease screening programmes based on the presence of two or more risk factors are failing to identify those with increased risk of diabetes and cardiovascular complications, thereby limiting early interventions. Screening that includes erythrocyte oxidative stress determination may provide an additional marker for both preclinical and advanced disease. In this review, a concise description of the involvement of erythrocyte oxidative stress in diabetes mellitus and its cardiovascular sequelae is presented. Antioxidant action and interaction in the erythrocyte are also described, with emphasis on why current coronary artery disease screening markers cannot be regarded as erythrocyte oxidative stress markers.

IRIS II study: the IRIS II score--assessment of a new clinical algorithm for the classification of insulin resistance in patients with Type 2 diabetes.

AIMS: With the increasing availability of new drugs for the treatment of insulin resistance in patients with Type 2 diabetes, simple methods for their identification is an important challenge. The aim of our study was to compute a new algorithm for estimating insulin resistance in a routine clinical setting. METHODS: Clinical data and blood samples were collected from 4265 Type 2 diabetic patients from 149 clinical sites. A clinical algorithm to estimate insulin resistance was developed by stepwise multiple regression analysis. The new generated score was compared with the HOMAIR-score, calculated from fasting insulin and glucose levels measured in a central laboratory. In a subgroup of 48 patients, the score was verified against a frequently sampled intravenous glucose tolerance test with subsequent modified minimal model analysis according to Bergman. RESULTS: Multiple regression analysis revealed fasting blood glucose, BMI, triglycerides and HDL as the most powerful predictors of insulin resistance which were used for further computation of the IRIS II score. A significant overall correlation was found between the HOMAIR-score and the new clinical IRIS II score (r = 0.42; P < 0.0001). Compared with HOMAIR, the new score revealed a specificity of 0.95, a sensitivity of 0.34 and a positive predictive value of 0.95. This was in good agreement with the subset analysis of the intravenous glucose tolerance test, where a sensitivity of 0.37 and a specificity of 0.85 of the IRIS II score was calculated. Patients with insulin resistance according to the IRIS II score revealed an increased odds ratio for overall vascular complications (1.28; 1.11-1.46; P < 0.001). CONCLUSIONS: The new IRIS II score can identify insulin resistance in Type 2 diabetic patients with high predictive value and high specificity.

[Prevalence and management of arterial hypertension in diabetic patients treated with insulin]. / Prévalence et prise en charge de l'hypertension artérielle chez les diabétiques traités par insuline.

In small series of selected hypertensive diabetic patients the short-term benefit of antihypertensive treatments is well documented. The purpose of this study was to analyse the management of arterial hypertension in a cohort of 612 insulin-treated diabetic out-patients routinely and consecutively examined in a diabetologic clinic between January 1, 1985 and April 1, 1986. The prevalence of arterial hypertension (i.e. patients with blood pressure values greater than or equal to 160 and/or 95 mmHg or on antihypertensive treatment) was 38 per cent (232 patients). One hundred and eighty-two patients (29.7 per cent) received an antihypertensive treatment (one drug 78 per cent, two drugs 17 per cent, three drugs 5 per cent). In decreasing order of frequency these drugs were: beta-blockers, diuretics, central acting agents, angiotensin-converting enzyme inhibitors and calcium antagonists. In treated hypertensive diabetic patients the mean +/- SD systolic blood pressure (157.1 +/- 19.1 mmHg) and diastolic pressure (85.3 +/- 9.3 mmHg) remained higher than in patients without antihypertensive treatment (133.4 +/- 17.2 and 77.8 +/- 8.3 mmHg respectively). One hundred and forty-two diabetic patients still had blood pressure values greater than or equal to 160 and/or 95 mmHg during visits; 92 were on antihypertensive treatment, 50 were untreated. In hypertensive diabetic patients the mean total glycosylated haemoglobin (HbA1) level was higher than in normotensive diabetic patients (9 +/- 1.6 versus 8.6 +/- 1.8; P less than 0.05). Hypertensive insulin-treated diabetics are the most seriously ill patients, they are under inadequate care. Wrong choice of antihypertensive drugs, incorrect goals of blood pressure reduction, lack of information and education to improve compliance were the main reasons for the poor results of this study.