Diabetes und Depression

Background

One of four patients with type 2 diabetes mellitus (T2DM) has clinically relevant depression. On the other hand, depression increases the risk for T2DM as well as micro- and macrovascular complications.

Objectives

This association may reflect a shared pathophysiology consisting of complex bidirectional interactions, which may influence therapy and prognosis.

Materials and methods

Recent findings, reviews and basic literature are analysed and an update is presented and discussed.

Results

Overall, accumulating evidence indicates a metabolic–mood syndrome with a linkage that includes stress sensitivity, insulin resistance (IR), neurohormonal dysregulation and inflammation. IR alters dopamine turnover and causes depression-like behaviour. Furthermore IR is associated with worse memory performance. Metabolic risk influences neurodevelopment. However, cross-sectional data do not support a genetic association between T2DM and depression.

Conclusions

T2DM may promote depression and interact with neurodevelopment and neurodegeneration. Comorbidity seems to be particularly toxic. Both prevention of T2DM in depressed patients and treatment of depression in T2DM are of considerable significance. Serotonin reuptake inhibition (SSRI) and psychotherapy are effective in the treatment of depression.

     

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.

     

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.

     

The Gut Microbiome as a Target for the Treatment of Type 2 Diabetes

Purpose of Review

The objective of this review is to critically assess the contributing role of the gut microbiota in human obesity and type 2 diabetes (T2D).

Recent Findings

Experiments in animal and human studies have produced growing evidence for the causality of the gut microbiome in developing obesity and T2D. The introduction of high-throughput sequencing technologies has provided novel insight into the interpersonal differences in microbiome composition and function.

Summary

The intestinal microbiota is known to be associated with metabolic syndrome and related comorbidities. Associated diseases including obesity, T2D, and fatty liver disease (NAFLD/NASH) all seem to be linked to altered microbial composition; however, causality has not been proven yet. Elucidating the potential causal and personalized role of the human gut microbiota in obesity and T2D is highly prioritized.

     

Incident Type 2 Diabetes Risk is Influenced by Obesity and Diabetes in Social Contacts: a Social Network Analysis

BACKGROUND

Obesity and diabetes family history are the two strongest risk factors for type 2 diabetes (T2D). Prior work shows that an individual’s obesity risk is associated with obesity in social contacts, but whether T2D risk follows similar patterns is unknown.

OBJECTIVE

We aimed to estimate the relationship between obesity or diabetes in an individual’s social contacts and his/her T2D risk. We hypothesized that obesity and diabetes in social contacts would increase an individual’s T2D risk.

DESIGN

This was a retrospective analysis of the community-based Framingham Offspring Study (FOS).

PARTICIPANTS

FOS participants with T2D status, height and weight, and at least one social contact were eligible for this study (n?=?4797 at Exam 1). Participants’ interpersonal ties, cardiometabolic and demographic variables were available at eight exams from 1971 to 2008, and a T2D additive polygenic risk score was measured at the fifth exam.

MAIN MEASURES

Primary exposures were T2D (fasting glucose?≥?7 mmol/L or taking diabetes medications) and obesity status (BMI?≥?30 kg/m²) of social contacts at a prior exam. Primary outcome was incident T2D in participants.

KEY RESULTS

Incident T2D was associated with having a social contact with diabetes (OR 1.32, p?=?0.004) or with obesity (OR 1.21, p?=?0.004). In stratified analyses, incident T2D was associated with diabetes in siblings (OR 1.64, p?=?0.001) and obesity in spouses (OR 1.54, p =?0.0004). The associations between diabetes and obesity in social contacts and an individual’s incident diabetes risk were stronger in individuals with a high diabetes genetic risk score.

CONCLUSIONS

T2D and obesity in social contacts, particularly siblings and spouses, were associated with an individual’s risk of incident diabetes even after accounting for parental T2D history. Assessing risk factors in an individual’s siblings and spouses can inform T2D risk; furthermore, social network based lifestyle interventions involving spouses and siblings might be a novel T2D prevention approach.

     

Inflammation Markers in Type 2 Diabetes and the Metabolic Syndrome in the Pediatric Population

Purpose of Review

Chronic inflammation, adipokines, and hepatokines have been identified as basis of insulin resistance and β cell failure in animal models. We present our current knowledge concerning the potential relationship between these cytokines, inflammation, metabolic syndrome (MetS), and type 2 diabetes mellitus (T2DM) in the pediatric population.

Recent Findings

Pro-inflammatory cytokines related to insulin resistance and MetS in children are tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, interferon gamma, pigment epithelium-derived factor, chemerin, vaspin, and fetuin A. Anti-inflammatory cytokines associated with insulin resistance and MetS in children are leptin, adiponectin, omentin, fibroblast growth factor (FGF)-21, osteocalcin, and irisin. These anti-inflammatory cytokines are decreased (adiponectin, omentin, and osteocalcin) or increased (leptin, FGF-21, and irisin) in obesity suggesting a resistance state. TNF-α, fetuin A, and FGF-21 are altered in obese children with T2DM suggesting an involvement in β cell failure.

Summary

These cytokines, adipokines, and hepatokines may be able to predict development of MetS and T2DM and have a potential therapeutic target ameliorating insulin resistance.

     

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.

     

Sugar-Sweetened Beverage,Obesity, and Type 2 Diabetes in Children and Adolescents: Policies,Taxation, and Programs

Purpose of Review

Obesity has grown at an alarming rate in children and adolescents. Concurrently, consumption on sugar-sweetened beverages (SSBs) also rose significantly. This review provides an overview of obesity and type 2 diabetes mellitus (T2DM) related to SSBs and current policies restricting SSBs in schools, school-based interventions, and taxation on reducing SSB intake and obesity. We also discuss challenges of and future steps for these initiatives.

Recent Findings

Clinical and epidemiological studies suggest a strong association between SSB intake and obesity and T2DM. School food policies have been initiated at federal, state, and local levels. School-based interventions have shown positive effects on SSB intake and obesity reduction. Taxation on SSBs is promising in combating obesity and in generating revenue. Challenges towards compliance and implementation of the policies and programs exist.

Summary

The relationship between SSB and obesity and T2DM is a complex problem which requires comprehensive solutions. Continued efforts in restricting SSBs in schools are needed. Intervention programs should be tailored to age, gender, language, and culture and involve participation from families and local communities. Taxation can reduce SSB consumption by direct economic incentive, earmarking revenues to support healthy foods, and sending negative message. However, a higher tax rate may be necessary to have a measurable effect on weight.

     

Gender and Sex Differences in Adipose Tissue

Purpose of Review

As the ongoing epidemic of adult and childhood obesity grows, it puts a greater burden on individuals and the healthcare system due to increased prevalence of obesity-associated diseases. An important area that has gained much attention recently is the sex and gender difference related to obesity and associated complications. Basic science and clinical studies have now improved our understanding of obesity and have discovered adipose tissue biology to be key in metabolism.

Recent Findings

There is evidence related to the sex dichotomy in obesity in a variety of areas including adipocyte function, sex hormone effects, genetics, and metabolic inflammation leading to critical differences in adipose tissue biology.

Summary

The sex and gender difference in adipose tissue is a factor that should be considered when studying an individuals’ risk for obesity and metabolic dysfunction. This understanding is important for strategizing treatment and prevention measures.

     

Should Metformin Remain First-Line Medical Therapy for Patients with Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease? An Alternative Approach

Purpose of Review

With recent cardiovascular outcome trial (CVOT) results for antihyperglycemic medications, the treatment algorithm for patients with type 2 diabetes (T2DM) and atherosclerotic vascular disease (ASCVD) requires revision.

Recent Findings

All completed CVOTs have demonstrated CV safety of the tested medications, with some trials demonstrating CV efficacy. While metformin remains the first-line recommended medication for T2DM, 18–37% of the patients enrolled in the completed CVOTs were not treated with metformin, providing substantial power to assess CV outcomes independent of metformin. The safety and tolerability of metformin are indisputable, but there are no robust data proving its efficacy for either macro or microvascular disease outcomes. We should reconsider the primacy of metformin in the management of T2DM in patients with ASCVD.

Summary

This article will review the evidence for CV effects of antihyperglycemic agents (AHAs), and propose an evidence-based treatment algorithm for patients with T2DM and ASCVD.

     

Weight Management in Patients with Type 2 Diabetes: a Multidisciplinary Real-world Approach

Purpose of Review

Obesity and type 2 diabetes (T2D) are closely linked metabolic diseases. Most individuals with T2D are overweight or obese, which raises their cardiovascular risk. The etiology of both diseases is multifaceted, thus requiring a multidisciplinary approach to control them. This review describes the most effective multidisciplinary approach to weight management in patients with T2D in real-world clinical practice.

Recent Findings

Weight management programs in real-world clinical settings lead to long-term weight loss for up to 5 years.

Summary

Multidisciplinary approach to manage obesity and T2D through weight reduction is feasible in real-world clinical practice and is recommended as part of the treatment plan for patients with T2D who are overweight or obese. Recent data demonstrates that multidisciplinary approach to weight management in patients with T2D results in long-term weight loss and is associated with improved cardiovascular risk factors.

     

Weight Loss and Overactive Bladder

Purpose of Review

We sought to explore the relationship between obesity and overactive bladder (OAB) and to review the available literature that supports weight loss as a means to alter OAB severity and bother.

Recent Findings

Over the past 15 years, several population-based human studies and animal models have identified obesity as a risk factor for the development of OAB. The bariatric surgery literature demonstrates that substantial weight loss following some form of gastric bypass can lead to at least subjective improvement in OAB symptoms. Ongoing research seeks to further elucidate the role of anti-inflammatory agents, anti-oxidants, and β3-receptor agonists in obesity-associated OAB.

Summary

The currently available literature has identified obesity as a risk factor for the development OAB. Data taken from the bariatric surgery literature indicates that surgical weight loss can lead to a significant improvement in OAB severity and bother. Future studies will determine if less dramatic weight changes can lead to significant and sustained changes in OAB parameters. Based on the available literature, clinicians should start to counsel their obese patients with OAB that weight loss can help improve their OAB severity and bother.

     

Anti-MDA5 Antibody Spectrum in Western World

Purpose of Review

Anti-melanoma differentiation-associated gene 5 (anti-MDA5) is a novel and highly specific myositis-associated autoantibody, which defines a unique phenotype among patients with dermatomyositis (DM).

Recent Findings

Anti-MDA5 was originally characterized in Japan in DM patients with hallmark cutaneous features and no proximal muscle weakness and termed clinically amyopathic DM (CADM). Anti-MDA5 has characteristic cutaneous manifestations which include tender palmar papules and cutaneous ulcerations, along with an increased frequency of interstitial lung disease (ILD) that can be rapidly progressive (RPILD) and fatal.

Summary

This review will highlight the clinical significance of anti-MDA5 autoantibodies in Caucasian DM patients.

     

Bariatric Surgery Prior to Total Joint Arthroplasty,Does it Decrease the Risk of Obesity Related Perioperative Complications?

Purpose of Review

The purpose of this review paper is to provide an overview of the relationship between obesity, osteoarthritis, arthroplasty outcomes, and the potential use of bariatric surgery to improve these outcomes.

Recent Findings

Unfortunately, the findings in the currently available literature evaluating the role of bariatric surgery prior to arthroplasty surgery largely rely on retrospective data and their results are somewhat conflicting.

Summary

Future prospective studies are needed to further evaluate whether or not bariatric surgery prior to arthroplasty surgery may be of benefit for patients. Additional research is needed to identify other methods to minimize complications that obese patients are particularly prone to developing following arthroplasty surgery.

     

Prevalence and predictors of delayed gastric emptying among Indian patients with long-standing type 2 diabetes mellitus

Background and Aims

Upper gastrointestinal symptoms are more prevalent among type 2 diabetes mellitus (T2DM) patients. The prevalence of delayed gastric emptying (GE) and factors predictive of it have not been studied in Indian T2DM patients and the present study aimed to study the same.

Methods

This hospital-based cross-sectional study involved adult (age between 18 and 65 years) outpatients with T2DM of ≥5-year duration. Measurements of GE of a labelled standardized solid rice idli meal by gastric emptying scintigraphy (GES), symptoms of delayed GE (by standardized questionnaire) and autonomic function by cardiovascular autonomic function tests (AFTs) were carried out. Thirty healthy subjects served as controls for GES and AFTs.

Results

One hundred and forty T2DM patients (age range: 32–65 years) were studied. Delayed GE was documented in ≈29 % (40/140) and rapid GE in 2 % (3/140) of T2DM patients. Univariate analysis showed significant positive association between delayed GE and duration of DM, body mass index (BMI), HbA1c, retinopathy, peripheral neuropathy, autonomic dysfunction and coronary artery disease (p < 0.05 for all). However, there was no significant correlation of age, sex, symptoms suggestive of gastroparesis and nephropathy with delayed GE. Hypoglycemic episodes were significantly more frequent in those with delayed GE (p < 0.05). Multiple logistic regression analysis revealed only BMI and HbA1c to be significant independent predictors of delayed GE.

Conclusion

Presence and severity of symptoms of gastroparesis did not predict delayed GE. Delayed GE, irrespective of symptoms, was associated with microvascular and macrovascular diabetic complications and increased risk of hypoglycemic episodes. HbA_1c and BMI were independent predictors of delayed GE.

     

Risk factors for non-alcoholic fatty liver disease are common in patients with non-B non-C hepatocellular carcinoma in India

Aim of the study

The aim of the study was to analyze the prevalence of risk factors for non-alcoholic fatty liver disease (NAFLD) in patients with non-B non-C hepatocellular carcinoma (HCC).

Methods

Between June 2012 and November 2014, patients with HCC, negative for hepatitis B surface antigen and hepatitis C virus antibody, were included in this study. All patients were assessed for risk factors for NAFLD such as diabetes mellitus (DM), hypertension, dyslipidemia, metabolic syndrome, and obesity.

Results

Forty-seven patients with non-B non-C HCC (males, 37; age, 60±10 years; mean±SD) were studied. Model for end-stage liver disease score was 11±4. Twenty-five patients were in Child’s class A. History of significant alcohol intake was noted in 11 (23%) patients. Prevalence of risk factors for NAFLD were obesity 24 (51%), DM 22 (47%), metabolic syndrome 21 (45%), hypertension 16 (34%), and dyslipidemia 13 (28%). Forty (85%) patients had at least one risk factor for NAFLD. The mean duration of at least one NAFLD risk factor was 7.5 years, prior to diagnosis of HCC. Thirteen (28%) patients were positive for anti-HBc; however, none of the study patients had detectable HBV DNA in blood.

Conclusions

Eighty-five percent of the patients with non-B non-C HCC had at least one risk factor for NAFLD. None of the study patients had occult hepatitis B infection. NAFLD is emerging as the major etiological contributing factor for non-B non-C HCC in India.

     

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.

     

Surgical Issues in NASH: Bariatric Surgery and Liver Transplantation

Purpose of Review

The rising prevalence of obesity in general and non-alcoholic steatohepatitis (NASH) specifically as an indication for liver transplantation has occurred in parallel with an increase in the consideration and performance of bariatric surgery before and after liver transplantation. We review the impact and relative merits of bariatric surgery before, during, and after liver transplantation.

Recent Findings

The sleeve gastrectomy approach has several practical advantages over other forms of weight loss surgery and has been shown to improve metabolic parameters. Bariatric surgical procedures inevitably affect immunosuppression pharmacokinetics, with the least impact being observed following sleeve gastrectomy. In the non-transplant setting, bariatric surgery has been shown to be an effective therapy for histological features of NASH.

Summary

When compared to lifestyle changes alone, bariatric surgery performed during or after liver transplantation results in sustained weight loss and improved metabolic parameters associated with liver disease, cardiovascular risk, and overall mortality. Further studies are needed to confirm which surgical procedures, timing, and NASH patients will receive most benefit.

     

Altered glucose profiles and risk for hypoglycaemia during oral glucose tolerance testing in pregnancies after gastric bypass surgery

Aims/hypothesis

A history of gastric bypass surgery can influence the results of the OGTT recommended during pregnancy. Therefore, we compared OGTT glucose kinetics and pregnancy outcome between pregnant gastric bypass patients and BMI-matched, lean and obese controls.

Methods

Medical records were used to collect data on glucose measurements during the 2 h 75 g OGTT as well as on pregnancy and fetal outcome for 304 women (n?=?76 per group, matched for age and date of delivery).

Results

Women after bariatric surgery had lower fasting glucose levels compared with lean, obese and BMI-matched controls, and showed altered postprandial glucose kinetics, including a rise at 60 min followed by hypoglycaemia with serum glucose of <3.34 mmol/l (which occurred in 54.8%). Moreover, their risk of pre-eclampsia or gestational hypertension was reduced, with an increased risk of delivering small for gestational age infants.

Conclusions/interpretation

Alternative strategies to accurately define impaired glucose metabolism in pregnancies after bariatric surgery should be explored.

     

An Overview of Metabolic Phenotyping in Blood Pressure Research

Purpose of the Review

This review presents the analytical techniques, processing and analytical steps used in metabolomics phenotyping studies, as well as the main results from epidemiological studies on the associations between metabolites and high blood pressure.

Recent Findings

A variety of metabolomic approaches have been applied to a range of epidemiological studies to uncover the pathophysiology of high blood pressure. Several pathways have been suggested in relation to blood pressure including the possible role of the gut microflora, inflammatory, oxidative stress, and lipid pathways. Metabolic changes have also been identified associated with blood pressure lowering effects of diets high in fruits and vegetables and low in meat intake. However, the current body of literature on metabolic profiling and blood pressure is still in its infancy, not fully consistent and requires careful interpretation.

Summary

Metabolic phenotyping is a promising approach to uncover metabolic pathways associated with high blood pressure and throw light into the complex pathophysiology of hypertension.