Biopsychosocial Aspects of Weight Management in Type 1 Diabetes: a Review and Next Steps

Purpose of Review

This review aims to summarize the type 1 diabetes (T1D) and weight literature with an emphasis on barriers associated with weight management, the unique T1D-specific factors that impact weight loss success, maladaptive and adaptive strategies for weight loss, and interventions to promote weight loss.

Recent Findings

Weight gain is associated with intensive insulin therapy. Overweight and obese weight status in individuals with T1D is higher than the general population and prevalence is rising. A variety of demographic (e.g., female sex), clinical (e.g., greater insulin needs), environmental (e.g., skipping meals), and psychosocial (e.g., depression, stress) factors are associated with overweight/obese weight status in T1D. Fear of hypoglycemia is a significant barrier to engagement in physical activity. Studies evaluating adaptive weight loss strategies in people with T1D are limited.

Summary

There is a growing literature highlighting the prevalence and seriousness of overweight and obesity among both youth and adults with T1D. There is an urgent need to develop evidence-based weight management guidelines and interventions that address the unique concerns of individuals with T1D and that concurrently address glycemic control.

     

Cannabinoid Receptors in Diabetic Kidney Disease

Purpose of Review

The purpose of this review is to examine and summarize studies assessing the relevance of the endocannabinoid system (ECS) in diabetic kidney disease (DKD).

Recent Findings

Endocannabinoids and endocannabinoid receptors of type 1 (CB1R) and of type 2 (CB2R) are present in the normal kidney. Expression of CB1R and CB2R is altered in experimental DKD. Studies in experimental animals and cultured kidney cells show a beneficial effect of peripheral CB1R blockade and CB2R activation in DKD and an even greater efficacy of a combined treatment.

Summary

Preclinical studies confirm that both CB1R and CB2R are implicated in the pathogenesis of DKD and may represent novel targets for treatment. However, we need to gain a better understanding of the ECS prior to move to human clinical trial.

     

The Landscape of Diabetic Kidney Disease in the United States

Purpose of Review

The purposes of this review are to identify population characteristics of important risk factors for the development and progression of diabetic kidney disease (DKD) in the United States and to discuss barriers and opportunities to improve awareness, management, and outcomes in patients with DKD.

Recent Findings

The major risk factors for the development and progression of DKD include hyperglycemia, hypertension, and albuminuria. DKD disproportionately affects minorities and individuals with low educational and socioeconomic status. Barriers to effective management of DKD include the following: (a) limited patient and healthcare provider awareness of DKD, (b) lack of timely referrals of patients to a nephrologist, (c) low patient healthcare literacy, and (d) insufficient access to healthcare and health insurance.

Summary

Increased patient and physician awareness of DKD has been shown to enhance patient outcomes. Multifactorial and multidisciplinary interventions targeting multiple risk factors and patient/physician education may provide better outcomes in patients with DKD.

     

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.

     

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.

     

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.

     

Systemische Vitamin-D-Wirkung und Typ-2-Diabetes

Background

Type 2 diabetes (T2D) is one of the most important chronic diseases with continuously rising numbers of patients. Vitamin D (VD) has been found to be deficient in several diseases. The 25(OH)D₃ serum level is commonly used as an indicator of the VD status.

Objectives

In order to obtain a balanced overview on associations between VD and T2D, recent publications were reviewed.

Results

Low VD status is associated with an increased incidence of T2D and its micro- and macrovascular complications. VD supplementation reduced insulin resistance in patients with T2D in some interventional studies; in other studies, no improvement was observed.

Conclusion

There is a correlation between VD status and T2D. In several studies VD supplementation in T2D showed significant, positive effects on metabolism, which was not confirmed in others. Due to the heterogeneous designs, these studies are hardly comparable; therefore, further controlled trials with well-defined endpoints are required.

     

Fat Versus Carbohydrate-Based Energy-Restricted Diets for Weight Loss in Patients With Type 2 Diabetes

Purpose of Review

The prevalence of combined obesity and diabetes has increased dramatically in the last few decades. Although medical and surgical weight management are variably effective in addressing this epidemic, it is essential to parallel these strategies with a hypocaloric diet comprising the appropriate macronutrient composition to induce weight loss, enhance glycemic control, and improve cardiovascular risk factors. This review reports the current evidence of the role of carbohydrates and fat-based diets for weight management in patients with combined type 2 diabetes (T2D) and obesity.

Recent Findings

Low-carbohydrate diets were shown to decrease postprandial glucose levels whereas high-carbohydrate, low-fat diets are considered cardio-protective.

Summary

A diet with an optimal macronutrient composition remains uncertain for patients with combined T2D and obesity. Further research is still needed to define the best dietary composition that achieves the maximum benefits on weight management, glycemic control, and cardiovascular risk factors.

     

Shared Genetic Contribution of Type 2 Diabetes and Cardiovascular Disease: Implications for Prognosis and Treatment

Purpose of Review

The increased cardiovascular disease (CVD) risk in subjects with type 2 diabetes (T2D) is well established. This review collates the available evidence and assesses the shared genetic background between T2D and CVD: the causal contribution of common risk factors to T2D and CVD and how genetics can be used to improve drug development and clinical outcomes.

Recent Findings

Large-scale genome-wide association studies (GWAS) of T2D and CVD support a shared genetic background but minimal individual locus overlap.

Summary

Mendelian randomisation (MR) analyses show that T2D is causal for CVD, but GWAS of CVD, T2D and their common risk factors provided limited evidence for individual locus overlap. Distinct but functionally related pathways were enriched for CVD and T2D genetic associations reflecting the lack of locus overlap and providing some explanation for the variable associations of common risk factors with CVD and T2D from MR analyses.

     

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.

     

Factors Associated with HIV Testing among African American Female Adolescents in Juvenile Detention Centers

Background

Little is known about sexual and psychosocial factors associated with HIV testing among detained African American female adolescents—an understudied group at risk for HIV.

Methods

188 detained African American female adolescents completed assessments on HIV testing, sexual risk behaviors, and psychosocial factors.

Results

Unprotected vaginal sex, history of STI-positivity or pregnancy, higher STI knowledge, and lower partner availability were associated with a higher likelihood of ever being tested for HIV.

Discussion

HIV testing is the gateway to important services for high-risk HIV-positive and HIV-negative adolescents. More research is needed to address barriers and to inform programmatic changes to increase testing among youth.

     

Role of the Immune System in Diabetic Kidney Disease

Purpose of Review

The purpose of this review is to examine the proposed role of immune modulation in the development and progression of diabetic kidney disease (DKD).

Recent Findings

Diabetic kidney disease has not historically been considered an immune-mediated disease; however, increasing evidence is emerging in support of an immune role in its pathophysiology. Both systemic and local renal inflammation have been associated with DKD. Infiltration of immune cells, predominantly macrophages, into the kidney has been reported in a number of both experimental and clinical studies. In addition, increased levels of circulating pro-inflammatory cytokines have been linked to disease progression. Consequently, a variety of therapeutic strategies involving modulation of the immune response are currently being investigated in diabetic kidney disease.

Summary

Although no current therapies for DKD are directly based on immune modulation many of the therapies in clinical use have anti-inflammatory effects along with their primary actions. Macrophages emerge as the most likely beneficial immune cell target and compounds which reduce macrophage infiltration to the kidney have shown potential in both animal models and clinical trials.

     

Advances in the Genetics of Youth-Onset Type 2 Diabetes

Purpose of Review

To provide an update on knowledge the role of genetics in youth-onset type 2 diabetes (T2D).

Recent Findings

The prevalence in youth of T2D, once thought to be exclusively a disease of adults, has increased by over 35% since 2001. Youth with T2D tend to have higher rates of complications, more aggressive disease, with more rapid loss of beta-cell function and a less favorable response to treatment than adults. Obesity is the most important risk factor for T2D, and the rise in childhood overweight and obesity appears responsible for the dramatic increase in T2D in youth. However, some obese children do not develop T2D, consistent with genetic differences in susceptibility to the disease in the setting of obesity and insulin resistance, currently far less well characterized in youth than in adults. Recent studies have begun to show associations of several established adult T2D genetic risk variants with youth-onset T2D and related glycemic quantitative traits, including the strongest known cross-population T2D genetic contributor TCF7L2. Maturity-onset diabetes of the young (MODY), a diabetes subtype distinct from type 1 diabetes (T1D) and T2D, is now known to result from a highly penetrant gene mutation in one of several genes. MODY has been shown to account for or contribute to at least 4.5% of clinically diagnosed T2D, even among those who are overweight or obese, impacting treatment decisions. The recently formed ProDiGY (Progress in Diabetes Genetics in Youth) Consortium is using genome-wide association studies and whole exome sequencing to understand the genetic architecture of T2D in youth, including how it differs from that of adults.

Summary

The limited amount of research conducted to date on the genetics of youth-onset T2D, which tends to be a more aggressive disease than adult T2D, suggests some overlap with genes involved in adult T2D and a sizeable influence of highly penetrant monogenic diabetes variants. The ProDiGY Consortium is expected to provide a more comprehensive understanding of youth T2D genetics.

     

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.

     

Family-Based Interventions Targeting Improvements in Health and Family Outcomes of Children and Adolescents with Type 1 Diabetes: a Systematic Review

Purpose of Review

A systematic review was conducted of family-based interventions to improve glycemic control, adherence, and psychosocial outcomes in children and adolescents with type 1 diabetes (T1D). Electronic databases were searched for randomized controlled trials (RCTs) published since the seminal Diabetes Control and Compliance Trial (DCCT). Interventions are summarized and findings reviewed to help guide clinical practice and future research.

Recent Findings

Twenty-five RCTs are reviewed. The majority of studies (n?=?15) focused on interventions targeting both children and adolescents and their caregivers and were delivered in diabetes clinics, outpatient settings, mental health clinics, or participants’ homes.

Summary

Family-based interventions for youth with T1D appear effective at improving diabetes and family-centered outcomes. Additional research is needed to examine the pathways to improvement in glycemic control, as outcomes were mixed. Future research should also involve measures beyond HbA1c given new markers for sustained health improvement and outcomes are being explored.

     

External Validation of a Tool Predicting 7-Year Risk of Developing Cardiovascular Disease,Type 2 Diabetes or Chronic Kidney Disease

Background

Chronic cardiometabolic diseases, including cardiovascular disease (CVD), type 2 diabetes (T2D) and chronic kidney disease (CKD), share many modifiable risk factors and can be prevented using combined prevention programs. Valid risk prediction tools are needed to accurately identify individuals at risk.

Objective

We aimed to validate a previously developed non-invasive risk prediction tool for predicting the combined 7-year-risk for chronic cardiometabolic diseases.

Design

The previously developed tool is stratified for sex and contains the predictors age, BMI, waist circumference, use of antihypertensives, smoking, family history of myocardial infarction/stroke, and family history of diabetes. This tool was externally validated, evaluating model performance using area under the receiver operating characteristic curve (AUC)—assessing discrimination—and Hosmer–Lemeshow goodness-of-fit (HL) statistics—assessing calibration. The intercept was recalibrated to improve calibration performance.

Participants

The risk prediction tool was validated in 3544 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab).

Key Results

Discrimination was acceptable, with an AUC of 0.78 (95% CI 0.75–0.81) in men and 0.78 (95% CI 0.74–0.81) in women. Calibration was poor (HL statistic: p?<?0.001), but improved considerably after intercept recalibration. Examination of individual outcomes showed that in men, AUC was highest for CKD (0.85 [95% CI 0.78–0.91]) and lowest for T2D (0.69 [95% CI 0.65–0.74]). In women, AUC was highest for CVD (0.88 [95% CI 0.83–0.94)]) and lowest for T2D (0.71 [95% CI 0.66–0.75]).

Conclusions

Validation of our previously developed tool showed robust discriminative performance across populations. Model recalibration is recommended to account for different disease rates. Our risk prediction tool can be useful in large-scale prevention programs for identifying those in need of further risk profiling because of their increased risk for chronic cardiometabolic diseases.

     

Ultra-Deep Genomic Sequencing of HCV NS5A Resistance-Associated Substitutions in HCV/HIV Coinfected Patients

Background and Aims

The prevalence of naturally occurring HCV-NS5A resistance-associated substitutions (RAS) to DAA drugs might affect the response to treatment in HCV/HIV coinfected subjects. There are limited data on the frequency of HCV-NS5A naturally occurring drug-RAS at baseline in HCV/HIV coinfected patients when ultra-deep sequencing methodologies are applied.

Methods

HCV-NS5A-RAS were evaluated among 25 subjects in each group. Patients were matched by age, gender, and hepatic fibrosis stage category to control for selection bias.

Results

Within subtype 1a, RAS were observed in 28% of HCV monoinfected and 48% of HCV/HIV coinfected subjects. More patients in the HCV/HIV coinfected group had clinically relevant mutations to DAA directed at NS5A.

Conclusion

While the clinical significance of this observation may be limited in highly drug adherent populations, some HCV/HIV coinfected persons may be at greater risk of viral resistance if suboptimal dosing occurs.

     

Presence of the posterior pituitary bright spot sign on MRI in the general population: a comparison between 1.5 and 3T MRI and between 2D-T1 spin-echo- and 3D-T1 gradient-echo sequences

Purpose

To describe the prevalence of the posterior pituitary bright spot (PPBS) in the general population on 1.5 and 3T MRI examinations and on 2D-T1 spin-echo (SE) and 3D-T1 gradient-echo (GE) sequences.

Materials and methods

1017 subjects who received an MRI of the brain for aspecific neurological complaints were included. MRI was performed on 1.5T in 64.5% and on 3T in 35.5% of subjects. Presence of the PPBS was evaluated on sagittal 2D T1-SE echo images with slice thickness 3 mm in 67.5% and on sagittal 3D T1-GE with slice thickness 0.9 mm in 32.5% of subjects.

Results

The PPBS was detectable in 95.9% of subjects. After correction for sex and age, no statistically significant difference could be seen concerning PPBS detection between 1.5 and 3T MRI examinations (p?=?0.533), nor between 2D T1-SE and 3D T1-GE sequences (p?=?0.217). There was a statistically significant association between increasing age and the absence of the PPBS (p?<?0.001). The PPBS could not be identified in 6.2% of male subjects, compared to 2.2% of female subjects (p?=?0.01).

Discussion

Absence of the PPBS can be seen in 4.1% of patients undergoing MRI of the brain for non-endocrinological reasons. Neither field-strength nor the use of a thick-sliced 2D T1-SE versus a thin-sliced 3D T1-GE sequence influenced the detectability of the PPBS. There is a statistically significant association between increasing age and male sex and the absence of the PPBS.

     

Sleep in Type 1 Diabetes: Implications for Glycemic Control and Diabetes Management

Purpose of Review

To highlight recent findings from studies of sleep in type 1 diabetes (T1D), with a focus on the role of sleep in self-management, the cognitive and psychosocial outcomes related to sleep disturbances, and factors associated with sleep disturbances specific to T1D.

Recent Findings

People with T1D experience higher rates of sleep disturbances than people without diabetes, and these disturbances have negative implications for glycemic control and diabetes management, as well as psychosocial and cognitive outcomes. Inconsistent sleep timing (bedtime and wake time) has emerged as a potential target for interventions, as variability in sleep timing has been linked with poorer glycemic control and adherence to treatment. Sleep-promoting interventions and new diabetes technology have the potential to improve sleep in people with T1D.

Summary

Sleep is increasingly considered a critical factor in diabetes management, but more multi-method and longitudinal research is needed. We emphasize the importance of sufficient and consistent sleep for people with T1D, and the need for providers to routinely assess sleep among patients with T1D.