Autonomic Regulation of Glucose Homeostasis: a Specific Role for Sympathetic Nervous System Activation

Purpose of Review

Cardiometabolic disorders such as obesity, metabolic syndrome and diabetes are increasingly common and associated with adverse cardiovascular outcomes. The mechanisms driving these developments are incompletely understood but likely to include autonomic dysregulation. The latest evidence for such a role is briefly reviewed here.

Recent Findings

Recent findings highlight the relevance of autonomic regulation in glucose metabolism and identify sympathetic activation, in concert with parasympathetic withdrawal, as a major contributor to the development of metabolic disorders and an important mediator of the associated adverse cardiovascular consequences.

Summary

Methods targeting sympathetic overactivity using pharmacological and device-based approaches are available and appear as logical additional approaches to curb the burden of metabolic disorders and alleviate the associated morbidity from cardiovascular causes. While the available data are encouraging, the role of therapeutic inhibition of sympathetic overdrive in the prevention of the metabolic disorders and the associated adverse outcomes requires adequate testing in properly sized randomised controlled trials.

     

Management of Dyslipidemia in Patients with Hypertension,Diabetes, and Metabolic Syndrome

Purpose of Review

The purpose of this review is to discuss dyslipidemia in the various common clinical conditions including hypertension, diabetes mellitus, and metabolic syndrome and review the current therapeutic strategy in these settings.

Recent Findings

Dyslipidemias are common in patients with hypertension, diabetes mellitus, and metabolic syndrome. Epidemiologic studies have shown a strong correlation between serum lipid levels and risk of atherosclerotic cardiovascular disease. Multifactorial intervention strategies aimed at controlling lipids, blood pressure, and blood glucose simultaneously achieve maximal reductions in cardiovascular risk.

Summary

Dyslipidemia and metabolic abnormalities are strongly associated with atherosclerosis and worse cardiovascular outcomes. While pharmacotherapy with statins has been proven to be beneficial for dyslipidemia, lifestyle modification emphasizing weight loss and regular exercise is an essential component of the interventional strategy. The common thread underlying atherosclerosis and metabolic abnormalities is endothelial dysfunction. Improved understanding of the role of endothelium in health and disease can potentially lead to novel therapies that may preempt development of atherosclerosis and its complications.

     

A Review of Data of Findings on Night Shift Work and the Development of DM and CVD Events: a Synthesis of the Proposed Molecular Mechanisms

Purpose of Review

Night shift work has become highly prevalent in our 24/7 societies, with up to 18% of the US work force working alternate shift schedules. However, studies indicate that there may be adverse health effects of chronic night work across diverse populations. These effects are likely due to misalignment of the circadian system with work schedules, mediated by the system’s primary marker melatonin as well as other downstream molecules.

Recent Findings

Melatonin has multiple biologic actions that are relevant to cardiometabolic disease, including modulation of oxidative stress, inflammation, and (via the melatonin receptor) vasoconstriction. Behavioral traits, such as chronotype and meal timing, have recently been shown to interact with the effects of night work on cardiometabolic health.

Summary

Together with recent findings suggesting a role for circadian genes in cardiometabolic risk, the interactions of night shift work and behavioral traits are likely to facilitate novel treatment and prevention approaches for cardiovascular disease and type 2 diabetes, incorporating aspects of clock and timing.

     

Blood Pressure Variability and Autonomic Dysfunction

Purpose of Review

This review considers the relationship between abnormal blood pressure (BP) variability and autonomic dysfunction through an attempt to answer questions about its clinical relevance and pertinence to diabetes and cardiovascular autonomic neuropathy (CAN) and which therapeutic measures can lessen its cardiovascular impact.

Recent Findings

Office, ambulatory, and home BP monitoring identify posture-related, circadian, short-term, and long-term BP variabilities. Abnormal BP variability is a risk marker for organ damage, mortality, and cardiovascular events. Moreover, BP variability changes are common in diabetes and associated with CAN and possibly exacerbated by comorbidities like nephropathy, obstructive sleep apnoea syndrome, and chronic pain. The prognostic role of nondipping and reverse dipping is well documented in diabetes. Some findings suggest the possibility of restoring dipping with the dosage time of antihypertensive agents.

Summary

Diabetes is a favorable scenario for altered BP variability, which might mediate the harmful effects of CAN. Preliminary data suggest the protective effect of targeting BP variability. However, further longitudinal outcome studies are needed. In the meantime, BP variability measures and practical expedients in antihypertensive treatment should be implemented in diabetes.

     

Population attributable fractions for Type 2 diabetes: an examination of multiple risk factors including symptoms of depression and anxiety

Background

Population attributable fractions (PAFs) are frequently used to quantify the proportion of Type 2 diabetes cases due to single risk factors, an approach which may result in an overestimation of their individual contributions. This study aimed to examine Type 2 diabetes incidence associated with multiple risk factor combinations, including the metabolic syndrome, behavioural factors, and specifically, depression and anxiety.

Methods

Using data from the population-based HUNT cohort, we examined incident diabetes in 36,161 Norwegian adults from 1995 to 2008. PAFs were calculated using Miettinen’s case-based formula, using relative risks estimated from multivariate regression models.

Results

Overall, the studied risk factors accounted for 50.5% of new diabetes cases (78.2% in men and 47.0% in women). Individuals exposed to both behavioural and metabolic factors were at highest risk of diabetes onset (PAF?=?22.9%). Baseline anxiety and depression contributed a further 13.6% of new cases to this combination. Men appeared to be particularly vulnerable to the interaction between metabolic, behavioural and psychological risk factors.

Conclusion

This study highlights the importance of risk factor clustering in diabetes onset, and is the first that we know of to quantify the excess fraction of incident diabetes associated with psychological risk factor interactions.

     

Type 2 Diabetes and Thiazide Diuretics

Purpose of Review

In patients with prediabetes or type 2 diabetes, the use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events, including new-onset diabetes.

Recent Findings

These metabolic disturbances are less marked with low-dose thiazides and, in most but not all studies, with thiazide-like diuretics (chlorthalidone, indapamide) than with thiazide-type diuretics (hydrochlorothiazide). In post hoc analyses of subgroups of patients with hypertension and type 2 diabetes, thiazides resulted in a significant reduction in cardiovascular events, all-cause mortality, and hospitalization for heart failure compared to placebo and generally were shown to be non-inferior to other antihypertensive agents.

Summary

Benefits attributed to thiazide diuretics in terms of cardiovascular event reduction outweigh the risk of worsening glucose control in type 2 diabetes and of new-onset diabetes in non-diabetic patients. Thiazides still play a key role in the management of patients with type 2 diabetes and hypertension.

     

Metabolic syndrome and risk of mortality in middle-aged versus elderly individuals: the Nord-Tr?ndelag Health Study (HUNT)

Aims/hypothesis

Recent reviews indicate that the metabolic syndrome is a risk factor for cardiovascular disease and mortality, but evidence is scarce in elderly individuals. We therefore examined the relationship between the metabolic syndrome and mortality rates among individuals aged 40–59, 60–74 and 75–89 years. We also examined whether the syndrome was associated with mortality rates over and above the Framingham risk score.

Methods

We studied prospectively 6,748 men and women who participated in the Nord-Trøndelag Health Study, Norway, from 1995 to 1997 (HUNT 2) and defined the metabolic syndrome by the International Diabetes Federation criteria.

Results

During 53,617 person-years of follow-up (mean per person, 7.9 years), 955 individuals died, of whom 585 died from cardiovascular disease. Among individuals who were 40–59 years of age at baseline, the presence of the metabolic syndrome was associated with increased relative risk of cardiovascular and total mortality (age- and sex-adjusted hazard ratios 3.97 [95% CI: 2.00–7.88] and 2.06 [1.35–3.13], respectively, equivalent to population-attributable risks of 20.7 and 14.2%, respectively). The Framingham risk score accounted for less than one-third of the effect of metabolic syndrome on mortality rates. After the age of 60 years, the metabolic syndrome was not associated with increased mortality rates. We found a significant interaction between the metabolic syndrome and age on the relative risk of mortality. Results were confirmed in a sub-sample without cardiovascular disease at baseline.

Conclusions/interpretation

The metabolic syndrome is a risk factor for mortality, over and above the Framingham risk score, in middle-aged, but not in elderly individuals.

     

Fettleberdiagnostik bei Diabetes mellitus Typ 2

Definition of terms

Under the term non-alcoholic fatty liver disease (NAFLD) both simple hepatic fat accumulation and non-alcoholic steatohepatitis (NASH) are combined. NASH is associated with liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC).

Epidemiological importance

In 2020, NAFLD will be the leading cause for liver transplantation in the USA, with rising financial costs for the healthcare system.

Comorbidities, diagnosis, and treatment

Type 2 diabetes (T2D) and metabolic syndrome (MetS) are important risk factors for the development of NAFLD, whereby these three diseases share similar pathophysiologic conditions, e.g., insulin resistance, obesity, and metabolic inflammation. Due to the rising number of patients with T2D and MetS, clinicians should aim to diagnose NAFLD early in this patient population and if necessary start treatment.

Goal

The aim of this work is to give an overview over the topic of NAFLD and diagnostic approaches in patients with T2D.

     

Diabetes und Hypertonie

Background

Diabetes mellitus is a disease which leads to vascular damage resulting in subsequent severe cardiovascular complications, such as myocardial infarction and stroke. This process is aggravated by coexisting hypertension.

Objective

This analysis gives a review of the latest study results on prognosis, blood pressure targets, drug therapy and interventional therapy in patients with diabetes and hypertension. Selected studies published in recent years with practical relevance for patients with diabetes and hypertension are presented.

Summary

Patients with simultaneous diabetes and hypertension have a poorer prognosis and a higher cardiovascular risk compared to patients with diabetes but without hypertension. Patients with diabetes and hypertension benefit from interventional blood pressure therapy

     

Gut Microbiome in Obesity,Metabolic Syndrome,and Diabetes

Purpose of Review

Obesity and diabetes are worldwide epidemics. There is also a growing body of evidence relating the gut microbiome composition to insulin resistance. The purpose of this review is to delineate the studies linking gut microbiota to obesity, metabolic syndrome, and diabetes.

Recent findings

Animal studies as well as proof of concept studies using fecal transplantation demonstrate the pivotal role of the gut microbiota in regulating insulin resistance states and inflammation.

Summary

While we still need to standardize methodologies to study the microbiome, there is an abundance of evidence pointing to the link between gut microbiome, inflammation, and insulin resistance, and future studies should be aimed at identifying unifying mechanisms.

     

Diabetes und Herz

Background

Diabetes remains a leading risk factor for cardiovascular events.

Current diabetes therapies

For the therapy of type 2 diabetes mellitus metformin is available as the first choice treatment. The decision which anti-diabetic drug should be used for second line therapy is left up to the treating physician. The decision-making process is largely influenced by the results of new cardiovascular outcome trials, which are carried for newly introduced diabetes medications.

Diabetes therapy and cardiovascular risk

Outcome studies for three classes of drugs were presented in the previous year, which are discussed in this article. Furthermore, this article presents recent advances in the possibilities for coronary interventions in patients with diabetes and mechanisms of diabetic cardiomyopathy are discussed.

     

The Impact of Metabolic Syndrome on the Outcome of NASH: Cirrhosis,Hepatocellular Carcinoma,and Mortality

Purpose of Review

In this review, we examine the interaction between the metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) and describe the impact of the features of MS on the most worrisome complications of non-alcoholic steatohepatitis (NASH), (cirrhosis, hepatocellular carcinoma) and, ultimately, on liver-related, cardiovascular, and overall mortality.

Recent Findings

Insulin resistance, obesity, and dyslipidemia in a pro-inflammatory environment have a causal role in hepatic fibrogenesis and oncogenesis in NAFLD patients. Natural history, longitudinal studies confirm the conditions linked to MS as independent predictors of overall-, cardiovascular-, and liver-related mortality.

Summary

Dysmetabolic factors stemming from insulin resistance play a key role in liver damage progression. Obesity, type 2 diabetes (T2DM), dyslipidemia, and arterial hypertension are independent predictors of liver fibrosis and cirrhosis; furthermore, obesity and T2DM play a key role in the development of hepatocellular carcinoma both in cirrhotic and non-cirrhotic NASH patients.

     

Thrombozytenfunktion

Background and objectives

Patients with diabetes mellitus are at increased cardiovascular risk. While arteriosclerotic lesions have long been recognized as the underlying cause, more recent studies suggest alterations in the coagulation system to be equally important in this context.

Materials and methods

A systematic PubMed search was performed.

Results

In patients with diabetes mellitus, alterations in the coagulation system play a pivotal role. This not only contributes to the increased cardiovascular risk but also explains the low or nonresponse to antiplatelet therapy. These alterations in the coagulation system include changes in platelet and fibrin clot function. This is reflected by the recommendation of the 2013 ESC guidelines on antiplatelet therapy in diabetes.

Conclusions

This article provides an overview of pathophysiological alterations in coagulation of patients with diabetes mellitus and the recommended antiplatelet therapy in the presence of coronary artery disease.

     

Sex differences in the prevalence of metabolic syndrome and its components in hypopituitary patients: comparison with an age- and sex-matched nationwide control group

Purpose

Hypopituitary patients have a reduced life expectancy owing to cardiovascular events. We investigated the prevalence of metabolic syndrome in hypopituitary patients for a follow-up period of at least 1 year in comparison with an age- and sex-matched nationwide control group.

Methods

A total of 515 patients with hypopituitarism who visited Seoul National University Hospital between January 2000 and December 2010 were included. Data for an age- and sex-matched control group were obtained from the Korean National Health and Nutrition Examination Surveys (KNHANES) (n = 1545). Metabolic syndrome was defined according to the modified National Cholesterol Education Program (NCEP-ATPIII).

Results

The prevalence of metabolic syndrome did not differ significantly between the hypopituitary and control groups for men (34.9 versus 30.3 %), but the risk of metabolic syndrome was higher in hypopituitary women than in controls (39.8 versus 28.5 %). In both sexes, the risks of central obesity and dyslipidemia were higher in the hypopituitary group than in the control group. Men had lower risks of hypertension and hyperglycemia in the hypopituitary group, which attenuated the risk of metabolic syndrome. Age greater than 40 years and obesity (BMI ≥25 kg/m²) contributed to a higher risk of metabolic syndrome.

Conclusions

The metabolic syndrome prevalence was higher in the hypopituitry group than in the control group in Korean women, and this was attributed to an increased risk of central obesity and dyslipidemia. Accordingly, early intervention to reduce metabolic syndrome needed in hypopituitary patients, i.e. women.

     

Financial Incentives and Diabetes Disease Control in Employees: A Retrospective Cohort Analysis

Background

Many employers offer worksite wellness programs, including financial incentives to achieve goals. Evidence supporting such programs is sparse.

Objective

To assess whether diabetes and cardiovascular risk factor control in employees improved with financial incentives for participation in disease management and for attaining goals.

Design

Retrospective cohort study using insurance claims linked with electronic medical record data from January 2008–December 2012.

Participants

Employee patients with diabetes covered by the organization’s self-funded insurance and propensity-matched non-employee patient comparison group with diabetes and commercial insurance.

Intervention

Financial incentives for employer-sponsored disease management program participation and achieving goals.

Main Measures

Change in glycosylated hemoglobin (HbA1c), low-density lipoprotein (LDL), systolic blood pressure (SBP), and weight.

Results

A total of 1092 employees with diabetes were matched to non-employee patients. With increasing incentives, employee program participation increased (7 % in 2009 to 50 % in 2012, p?<?0.001). Longitudinal mixed modeling demonstrated improved diabetes and cardiovascular risk factor control in employees vs. non-employees [HbA1c yearly change ?0.05 employees vs. 0.00 non-employees, difference in change (DIC) p <0.001]. In their first participation year, employees had larger declines in HbA1c and weight vs. non-employees (0.33 vs. 0.14, DIC p?=?0.04) and (2.3 kg vs. 0.1 kg, DIC p?<?0.001), respectively. Analysis of employee cohorts corresponding with incentive offerings showed that fixed incentives (years 1 and 2) or incentives tied to goals (years 3 and 4) were not significantly associated with HbA1c reductions compared to non-employees. For each employee cohort offered incentives, SBP and LDL also did not significantly differ in employees compared with non-employees (DIC p?>?0.05).

Conclusions

Financial incentives were associated with employee participation in disease management and improved cardiovascular risk factors over 5 years. Improvements occurred primarily in the first year of participation. The relative impact of specific incentives could not be discerned.

     

Independent associations between a metabolic syndrome severity score and future diabetes by sex and race: the Atherosclerosis Risk In Communities Study and Jackson Heart Study

Aims/hypothesis

The study aimed to assess for an association between the degree of severity of the metabolic syndrome and risk of type 2 diabetes beyond that conferred by the individual components of the metabolic syndrome.

Methods

We assessed HRs for an Adult Treatment Panel III (ATP-III) metabolic syndrome score (ATP-III MetS) and a sex- and race-specific continuous metabolic syndrome severity z score related to incident diabetes over a median of 7.8 years of follow-up among participants of two observational cohorts, the Atherosclerosis Risk in Communities study (n = 10,957) and the Jackson Heart Study (n = 2137).

Results

The ATP-III MetS had an HR for incident diabetes of 4.36 (95% CI 3.83, 4.97), which was attenuated in models that included the individual metabolic syndrome components. By contrast, participants in the fourth quartile of metabolic syndrome severity (compared with the first quartile) had an HR of 17.4 (95% CI 12.6, 24.1) for future diabetes; in models that also included the individual metabolic syndrome components, this remained significant, with an HR of 3.69 (95% CI 2.42, 5.64). There was a race × metabolic syndrome interaction in these models such that HR was greater for black participants (5.30) than white participants (2.24). When the change in metabolic syndrome severity score was included in the hazard models, this conferred a further association, with changes in metabolic syndrome severity score of ≥0.5 having a HR of 2.66 compared with changes in metabolic syndrome severity score of ≤0.

Conclusions/interpretation

Use of a continuous sex- and race-specific metabolic syndrome severity z score provided an additional prediction of risk of diabetes beyond that of the individual metabolic syndrome components, suggesting an added risk conferred by the processes underlying the metabolic syndrome. Increases in this score over time were associated with further risk, supporting the potential clinical utility of following metabolic syndrome severity over time.

     

Role of Mineralocorticoid Receptors in Obstructive Sleep Apnea and Metabolic Syndrome

Purpose of Review

This review will summarize recent developments in the research on the mineralocorticoid receptor and its impact on obstructive sleep apnea and metabolic syndrome.

Recent Findings

Aldosterone excess plays an important role in the association between resistant hypertension and obstructive sleep apnea. The prevalence of obesity is increasing rapidly worldwide and is especially common among patients with obstructive sleep apnea, resistant hypertension, and metabolic syndrome, suggesting probable mechanistic links between these three conditions. Mineralocorticoid receptor expression is increased in obese individuals, which may contribute to the common association between obesity and hyperaldosteronism. Mineralocorticoid receptor blockers reduce the severity of obstructive sleep apnea among resistant hypertension patients.

Summary

A large body of literature demonstrates a strong association between obesity, hyperaldosteronism, resistant hypertension, and sleep apnea, including specific benefit of treatment with mineralocorticoid receptor blockers for these separate disorders.

     

Vascular and Endothelial Function in Youth with Type 2 Diabetes Mellitus

Purpose of Review

This review aims to discuss the burden of type 2 diabetes in youth and summarize the studies that have utilized noninvasive techniques to assess early vascular disease in youth with type 2 diabetes.

Recent Findings

Noninvasive imaging modalities provide researchers with tools to investigate the vasculature in adolescents with type 2 diabetes. The data published to date consistently show adolescents with type 2 diabetes have greater vascular thickness and stiffness and worse endothelial function compared to their obese and lean peers.

Summary

As the prevalence of type 2 diabetes continues to increase adolescent youth, there is concern adolescents with type 2 diabetes are at risk to develop early onset cardiovascular disease and complications. Future studies need to address treatments that have the potential to improve or reverse vascular dysfunction and decrease the rate of cardiovascular disease and complications.

     

Prostate Cancer Survivorship: Prevention and Treatment of the Adverse Effects of Androgen Deprivation Therapy

BACKGROUND

More than one-third of the estimated 2 million prostate cancer survivors in the United States receive androgen deprivation therapy (ADT). This population of mostly older men is medically vulnerable to a variety of treatment-associated adverse effects.

MEASUREMENTS AND RESULTS

Androgen-deprivation therapy (ADT) causes loss of libido, vasomotor flushing, anemia, and fatigue. More recently, ADT has been shown to accelerate bone loss, increase fat mass, increase cholesterol and triglycerides, and decrease insulin sensitivity. Consistent with these adverse metabolic effects, ADT has also recently been associated with greater risks for fractures, diabetes and cardiovascular disease.

CONCLUSION

Primary care clinicians and patients should be aware of the potential benefits and harms of ADT. Screening and intervention to prevent treatment-related morbidity should be incorporated into the routine care of prostate cancer survivors. Evidence-based guidelines to prevent fractures, diabetes, and cardiovascular disease in prostate cancer survivors represent an important unmet need. We recommend the adapted use of established practice guidelines designed for the general population.