Diabetic microvascular complications as simple indicators of risk for cardiovascular outcomes and heart failure

No abstract available

Cardiovascular and mortality risks in migrant South Asians with type 2 diabetes: are we winning the battle?

Purpose of Review: We seek to describe the relationship between diabetes mellitus and cardiovascular risk in migrant South Asians compared to native white Europeans, and to determine the temporal change in this relationship over recent years. Recent Findings: Recent evidence suggests that the excess mortality risk associated with diabetes is lower in the migrant South Asian population compared with white Europeans. By contrast, South Asians continue to demonstrate elevated cardiovascular morbidity compared to white Europeans, although to a lesser extent than was observed in previous decades. Summary: The excess mortality previously observed in South Asian migrants has attenuated with a lower mortality risk compared to white Europeans observed in several recent studies. We speculate that these findings may relate in part to earlier diabetes diagnosis and more prolonged exposure to cardiovascular risk factor management in the South Asian population. Further study is required to confirm these hypotheses

Type 2 diabetes in migrant south Asians: mechanisms, mitigation, and management

South Asians, particularly when living in high-income countries, are at a substantially elevated risk of type 2 diabetes compared with white Europeans, and typically develop the disease 5–10 years earlier and at a lower BMI. Migrant south Asians seem to be more insulin resistant than white Europeans across the life course and potentially experience β-cell exhaustion at a younger age. Differences in adiposity (high percentage of body fat and high proportion of deep subcutaneous and visceral fat) and skeletal muscle (low percentage of lean mass and low cardiorespiratory fitness) are likely to contribute these factors. No clear evidence is available suggesting genetic factors make a major contribution to the increased risk of diabetes in south Asians, but epigenetic factors might have a role. Irrespective of future mechanistic discoveries, south Asians need to be encouraged and helped—by various culturally appropriate methods—to maintain a high physical activity level and low bodyweight across the life course to prevent diabetes. In clinical terms, cardiovascular risks have attenuated over time in migrant south Asians with diabetes but retinopathy and renal complication risks remain high because of the high levels of glycaemia and rapid glycaemic deterioration noted in this population. We review these aspects and suggest areas for future research

Glycaemic effects of non-statin lipid-lowering therapies

Since the publication of the JUPITER trial, attention has been focused on the adverse glycemic effects of statin therapy. Although the modest increase in the risk of new diabetes mellitus is outweighed by the reduction in cardiovascular events for statins, emerging biochemical and genetic links between lipid metabolism and glycemic control raise the prospect of a broader diabetogenic effect of lipid-lowering therapies. For the novel and powerful PCSK9-inhibitor class available evidence does not support a major glycaemic effect with the results of large scale trials awaited although preliminary genetic data does suggest a link. In contrast, there is clear evidence of a diabetogenic effect for the now outdated but well-studied niacin. For ezetimibe and fibrates, evidence is scarce but currently broadly unconcerning. For now, the glycemic effects of lipid-lowering therapies should have a limited influence on clinical decision-making. Further study in this topical area is needed

Advances in the clinical management of type 2 diabetes: a brief history of the past 15 years and challenges for the future

Remarkable progress has been made in some aspects of diabetes care over the last 15 years, but there have also been a rising number of challenges that differ between high and low-income countries. In high-income countries, a substantial increase in the use of preventative drugs for cardiovascular disease has lowered vascular complications and improved diabetes survival. More recently, new classes of diabetes drugs have emerged that can variably lower cardiovascular outcomes, new-onset heart failure and slow renal decline, thereby meaningfully increasing the diabetes armoury that should help patients to live even longer lives and with fewer complications. At the other end of the disease spectrum, we can now better prevent diabetes in people who are at elevated risk of developing it, whereas other new research has shown that diabetes remission is possible when lifestyle changes are made in the early years after diagnosis. The downside is that more people than ever before have type 2 diabetes, so despite such progress in high-income countries, the absolute burden of disease is rising. Furthermore, it is rising even faster in low and middle-income countries, where rising adiposity is driving a tidal wave of new diabetes cases; yet, healthcare systems are less able to cope, lacking sufficient drugs, trained personnel and integrated care systems. Thus, despite advances, the future challenges from rising diabetes rates worldwide are daunting

Research digest: new horizons in heart failure therapy

No abstract available

Management of lipid abnormalities in patients with diabetes

Purpose of Review: To describe lipid abnormalities in diabetes, when they occur and the evidence base for lipid management with established and new drugs to prevent diabetes complications. We also discuss how to manage statin intolerance. Recent Findings: Statins remain first-line therapy in patients with diabetes, though newer therapies to reduce LDL-C have emerged, including ezetimibe as an add-on therapy to statins, and injectable PCSK9 inhibitors, both of which are safe and effective in diabetes. Emerging evidence suggests a need to consider lipid-lowering therapies more often in younger patients with both type 1 and type 2 diabetes. Summary: Statins remain the cornerstone of lipid management in diabetes but other options are increasing. There is also now evidence for better managing apparent statin intolerance. Notably, younger patients lose the most life years from their diabetes, an observation that future guidelines need to consider

Applying metabolomics to cardiometabolic intervention studies and trials: past experiences and a roadmap for the future

Metabolomics and lipidomics are emerging methods for detailed phenotyping of small molecules in samples. It is hoped that such data will: (i) enhance baseline prediction of patient response to pharmacotherapies (beneficial or adverse); (ii) reveal changes in metabolites shortly after initiation of therapy that may predict patient response, including adverse effects, before routine biomarkers are altered; and( iii) give new insights into mechanisms of drug action, particularly where the results of a trial of a new agent were unexpected, and thus help future drug development. In these ways, metabolomics could enhance research findings from intervention studies. This narrative review provides an overview of metabolomics and lipidomics in early clinical intervention studies for investigation of mechanisms of drug action and prediction of drug response (both desired and undesired). We highlight early examples from drug intervention studies associated with cardiometabolic disease. Despite the strengths of such studies, particularly the use of state-of-the-art technologies and advanced statistical methods, currently published studies in the metabolomics arena are largely underpowered and should be considered as hypothesis-generating. In order for metabolomics to meaningfully improve stratified medicine approaches to patient treatment, there is a need for higher quality studies, with better exploitation of biobanks from randomized clinical trials i.e. with large sample size, adjudicated outcomes, standardized procedures, validation cohorts, comparison witth routine biochemistry and both active and control/placebo arms. On the basis of this review, and based on our research experience using clinically established biomarkers, we propose steps to more speedily advance this area of research towards potential clinical impact

Ethnic specific obesity cut-offs for diabetes risk: cross-sectional study of 490, 288 UK Biobank participants

OBJECTIVE To compare the relationship between adiposity and prevalent diabetes across ethnic groups in the UK Biobank cohort and to derive ethnic-specific obesity cutoffs that equate to those developed in white populations in terms of diabetes prevalence.<p></p> RESEARCH DESIGN AND METHODS UK Biobank recruited 502,682 U.K. residents aged 40–69 years. We used baseline data on the 490,288 participants from the four largest ethnic subgroups: 471,174 (96.1%) white, 9,631 (2.0%) South Asian, 7,949 (1.6%) black, and 1,534 (0.3%) Chinese. Regression models were developed for the association between anthropometric measures (BMI, waist circumference, percentage body fat, and waist-to-hip ratio) and prevalent diabetes, stratified by sex and adjusted for age, physical activity, socioeconomic status, and heart disease.<p></p> RESULTS Nonwhite participants were two- to fourfold more likely to have diabetes. For the equivalent prevalence of diabetes at 30 kg/m2 in white participants, BMI equated to the following: South Asians, 22.0 kg/m2; black, 26.0 kg/m2; Chinese women, 24.0 kg/m2; and Chinese men, 26.0 kg/m2. Among women, a waist circumference of 88 cm in the white subgroup equated to the following: South Asians, 70 cm; black, 79 cm; and Chinese, 74 cm. Among men, a waist circumference of 102 cm equated to 79, 88, and 88 cm for South Asian, black, and Chinese participants, respectively.<p></p> CONCLUSIONS Obesity should be defined at lower thresholds in nonwhite populations to ensure that interventions are targeted equitably based on equivalent diabetes prevalence. Furthermore, within the Asian population, a substantially lower obesity threshold should be applied to South Asian compared with Chinese groups.<p></p&gt