681 research outputs found
Metformin:A Narrative Review of Its Potential Benefits for Cardiovascular Disease, Cancer and Dementia
The biguanide metformin has been used as first-line therapy in type 2 diabetes mellitus (T2DM) treatment for several decades. In addition to its glucose-lowering properties and its prevention of weight gain, the landmark UK Prospective Diabetes Study (UKPDS) demonstrated cardioprotective properties in obese T2DM patients. Coupled with a favorable side effect profile and low cost, metformin has become the cornerstone in the treatment of T2DM worldwide. In addition, metformin is increasingly being investigated for its potential anticancer and neuroprotective properties both in T2DM patients and non-diabetic individuals. In the meantime, new drugs with powerful cardioprotective properties have been introduced and compete with metformin for its place in the treatment of T2DM. In this review we will discuss actual insights in the various working mechanisms of metformin and the evidence for its beneficial effects on (the prevention of) cardiovascular disease, cancer and dementia. In addition to observational evidence, emphasis is placed on randomized trials and recent meta-analyses to obtain an up-to-date overview of the use of metformin in clinical practice
Microvascular Dysfunction Is Associated With a Higher Incidence of Type 2 Diabetes Mellitus A Systematic Review and Meta-Analysis
Objective-Recent data support the hypothesis that microvascular dysfunction may be a potential mechanism in the development of insulin resistance. We examined the association of microvascular dysfunction with incident type 2 diabetes mellitus (T2DM) and impaired glucose metabolism by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic. Methods and Results-We searched Medline and Embase for articles published up to October 2011. Prospective cohort studies that focused on microvascular measurements in participants free of T2DM a baseline were included. Pooled relative risks were calculated using random effects models. Thirteen studies met the inclusion criteria for this meta-analysis. These studies focused on T2DM or impaired fasting glucose, not on impaired glucose tolerance. The pooled relative risks for incident T2DM (3846 cases) was 1.25 (95% confidence interval, 1.15; 1.36) per 1 SD greater microvascular dysfunction when all estimates of microvascular dysfunction were combined. In analyses of single estimates of microvascular dysfunction, the pooled relative risks for incident T2DM was 1.49 (1.36; 1.64) per 1 SD higher plasma soluble E-selectin levels; 1.21(1.11; 1.31) per 1 SD higher plasma soluble intercellular adhesion molecule-1 levels; 1.48 (1.03; 2.12) per 1 SD lower response to acetylcholine-mediated peripheral vascular reactivity; 1.18 (1.08; 1.29) per 1 SD lower retinal arteriole-to-venule ratio; and 1.43 (1.33; 1.54) per 1 logarithmically transformed unit higher albumin-to-creatinine ratio. In addition, the pooled relative risks for incident impaired fasting glucose (409 cases) was 1.15 (1.01-1.31) per 1 SD greater retinal venular diameters. Conclusion-These data indicate that various estimates of microvascular dysfunction were associated with incident T2DM and, possibly, impaired fasting glucose, suggesting a role for the microcirculation in the pathogenesis of T2DM. (Arterioscler Thromb Vasc Biol. 2012;32:3082-3094.
Methylglyoxal and glyoxalase I in atherosclerosis
Abstract Cardiovascular disease, caused predominantly by atherosclerotic plaque rupture, remains one of the leading causes of death. However, the mechanism of plaque rupture remains largely unknown. Recent studies have linked high metabolic activity in inflamed atherosclerotic plaques to the development of plaque rupture. AGEs (advanced glycation end-products) are known to be formed as a result of high metabolic activity and are higher in rupture-prone than stable plaques. Furthermore, AGEs seem to be more than mere markers of metabolic activity, as recent studies have elucidated that AGEs and their major precursor, MG (methylglyoxal), may have an important role in the progression of atherosclerosis and plaque rupture. MG can be detoxified by Glo1 (glyoxalase I), thereby preventing the accumulation of MG and MG-derived AGEs. In the present review, data concerning MG, Glo1 and AGEs in the context of plaque phenotype are discussed
Evidence for genetic factors explaining the association between birth weight and low-density lipoprotein cholesterol and possible intrauterine factors influencing the association between birth weight and high-density lipoprotein cholesterol: Analysis in twins
Recent studies have demonstrated an association between low weight at birth and an atherogenic lipid profile in later life. To examine the influences of intrauterine and genetic factors, we investigated 53 dizygotic and 61 monozygotic adolescent twin pairs. Regression analysis demonstrated that low birth weight was associated with high levels of total cholesterol, low-density lipoprotein (LDL) cholesterol and apolipoprotein B (-0.17 mmol/liter per kg, P = 0.07; -0.18 mmol/liter per kg, P = 0.04; and -0.07 g/liter per kg, P = 0.02, respectively) and with low levels of high-density lipoprotein (HDL) cholesterol (+0.04 mmol/liter per kg, P = 0.1), after adjustment for age, sex, and body mass index. Intrapair differences in birth weight were significantly associated with differences in total cholesterol, LDL cholesterol, and apolipoprotein B in dizygotic twins after adjustment for differences in current body mass index (-0.49 mmol/liter per kg, P = 0.02; -0.51 mmol/liter per kg, P = 0.01; and -0.10 g/liter per kg, P = 0.04, respectively), demonstrating that the larger the difference in birth weight, the higher these risk factors in the twin with the lower birth weight, compared with the cotwin with the higher birth weight. In monozygotic twins, however, the associations between intrapair differences in birth weight and differences in total cholesterol, LDL cholesterol, and apolipoprotein B were in the opposite direction (+0.32 mmol/liter per kg, P = 0.03; +0.23 mmol/liter per kg, P = 0.08; and +0.06 g/liter per kg, P = 0.04, respectively). The association between intrapair differences in birth weight and differences in HDL cholesterol was not significant in dizygotic twins (+0.04 mmol/liter per kg, P = 0.6) and of borderline significance in monozygotic twins (+0.11 mmol/liter per kg, P = 0.05). These data suggest that genetic factors account for the association of low birth weight with high levels of total cholesterol, LDL cholesterol, and apolipoprotein B, whereas intrauterine factors possibly play a role in the association between birth weight and HDL cholesterol
Association between arterial stiffness, cerebral small vessel disease and cognitive impairment: A systematic review and meta-analysis
Arterial stiffness may be a cause of cerebral small vessel disease and cognitive impairment. We therefore performed a systematic review and meta-analysis of studies on the association between stiffness, cerebral small vessel disease and cognitive impairment. For the associations between stiffness (i.e. carotid-femoral pulse wave velocity (cfPWV), brachial-ankle PVVV (baPWV), carotid stiffness and pulse pressure) on the one hand and cerebral small vessel disease and cognitive impairment on the other, we identified 23 (n = 15,666/20 cross-sectional; 1 longitudinal; 2 combined cross-sectional/longitudinal) and 41 studies (n= 57,671/26 cross-sectional; 11 longitudinal; 4 combined cross-sectional/longitudinal), respectively. Pooled analyses of cross-sectional studies showed that greater stiffness was associated with markers of cerebral small vessel disease with odds ratios, per +1 SD, of 1.29-1.32 (
Endoplasmic reticulum stress-induced apoptosis in the development of diabetes: is there a role for adipose tissue and liver?
Diabetes mellitus (DM) is a multifactorial chronic metabolic disease characterized by hyperglycaemia. Several different mechanisms have been implicated in the development of the disease, including endoplasmic reticulum (ER) stress. ER stress is increasingly acknowledged as an important mechanism in the development of DM, not only for β-cell loss but also for insulin resistance. Accumulating evidence suggests that ER stress-induced apoptosis may be an important mode of β-cell loss and therefore important in the development of diabetes. Recent data also suggest a role of ER stress-induced apoptosis in liver and adipose tissue in relation to diabetes, but more extensive studies on human adipocyte and hepatocyte (patho)physiology and ER stress are needed to identify the exact interactions between environmental signals, ER stress and apoptosis in these organs
The association of early life socioeconomic conditions with prediabetes and type 2 diabetes: results from the Maastricht study
markdownabstractBackground: Using cross-sectional data from The Maastricht Study, we examined the association of socioeconomic conditions in early life with prediabetes and T2DM in adulthood. We also examined potential mediating pathways via both adulthood socioeconomic conditions and adult BMI and health behaviours.
Methods: Of the 3263 participants (aged 40-75 years), 493 had prediabetes and 906 were diagnosed with T2DM. By using logistic regression analyses, the associations and possible mediating pathways were examined.
Results: Participants with low early life socioeconomic conditions had a 1.56 times higher odds of prediabetes (95% confidence interval (CI) = 1.21-2.02) and a 1.61 times higher odds of T2DM (95% CI = 1.31-1.99). The relation between low early life socioeconomic conditions and prediabetes was independent of current socioeconomic conditions (OR = 1.38, 95% CI = 1.05-1.80), whereas the relation with T2DM was not independent of current socioeconomic conditions (OR = 1.10, 95% CI = 0.87-1.37). BMI party mediated the association between early life socioeconomic conditions and prediabetes.
Conclusions: Socioeconomic inequalities starting in early life were associated with diabetes-related outcomes in adulthood and suggest the usefulness of early life interventions aimed at tackling these inequalities
Erratum to: Plasma levels of matrix metalloproteinase-2, -3, -10, and tissue inhibitor of metalloproteinase-1 are associated with vascular complications in patients with type 1 diabetes: the EURODIAB Prospective Complications Study
Endothelial Dysfunction Plays a Key Role in Increasing Cardiovascular Risk in Type 2 Diabetes The Hoorn Study
In the pathogenesis of cardiovascular events, interaction between risk factors has seldom been identified. However, endothelial dysfunction on the one hand and type 2 diabetes mellitus, impaired glucose metabolism (IGM), and insulin resistance on the other may act synergistically (ie, interact) in the development of cardiovascular disease. We therefore investigated the interaction between endothelial dysfunction and type 2 diabetes mellitus, IGM, and insulin resistance with regard to risk of cardiovascular events. In a prospective population-based cohort (n=445; 69 years; 55% women; 23% type 2 diabetes mellitus, 28% IGM [by design]), endothelial dysfunction (brachial artery flow-mediated dilatation), glucose tolerance (oral glucose tolerance test), and insulin sensitivity (homeostasis model assessment for insulin resistance [HOMA2-IR]) were determined. After a median follow-up of 7.6 years, 106 participants had had a cardiovascular event. After adjustments, 1 SD less flow-mediated dilatation was associated with cardiovascular events in type 2 diabetes mellitus (hazard ratio 1.69 [95% confidence interval, 1.14-2.52]) and IGM (1.50 [0.95-2.37]) and among those in the highest HOMA2-IR tertile (1.92 [1.42-2.60]), but not in normal glucose metabolism (0.85 [0.63-1.16]) or among those in the lower 2 HOMA2-IR tertiles combined (0.85 [0.65-1.12]). Interaction between flow-mediated dilatation and type 2 diabetes mellitus, IGM, or insulin resistance was present on an additive (relative excess risk caused by interaction >0) and on a multiplicative scale (P interactio
The renewable energy and energy efficiency potential of Waitakere City : a thesis presented in partial fulfilment of the requirements for the degree of Masters of Technology in Energy Management at Massey University
Electricity restrictions and blackouts have occurred in Waitakere City in the past and are likely to occur again in the future unless the city can become more self reliant by meeting, at least in part, the increasing energy requirements for what is one of the fastest growing cities in New Zealand. In this study the potentials for energy conservation, energy efficiency and renewable energy resources have been broadly quantified and assessed using desktop analysis of publicly available data for stationary final use energy systems (i.e. excluding transportation) within the geographical area of Waitakere City and adjoining waters.
It was found that energy efficiency and energy conservation measures can consistently and predictably achieve overall energy savings and reduce daily and seasonal peak demand.
The best renewable energy resource potential exists with solar and geothermal for heating applications and wave, offshore and inshore wind and tidal currents for electricity generation. There is very limited potential for hydro and bioenergy systems beyond what already exists. PV solar and land based wind power generation are currently only feasible for limited off-grid applications.
This scoping study confirms the achievability of the vision expressed in Waitakere City Council's "Long Term Council Community Plan" (LTCCP) that by 2020 " Waitakere City will be an energy cell, not an energy sink. Air quality supports good health". A range of flagship projects have been identified to progress the achievement of this vision. Waitakere City Council can use this report as part of the development of a comprehensive energy management plan
- …