Patrick Campbell

While multiple studies have linked glycemic variability in midlife to cognitive decline in diabetics, new research from the University of Cambridge suggests high insulin levels and BMI changes in childhood could signal a greater risk of psychosis and depression as a young adult in otherwise healthy patients.

An analysis of data from within the Avon Longitudinal Study of Parents and Children (ALSPAC), investigators suggest results outline the importance of diet and physical activity throughout life as avenues to modify risk of developing psychosis, depression, or other mental health disorders later in life.

"The general assumption in the past has been that some people with psychosis and depression might be more likely to have a poor diet and lower levels of physical exercise, so any adverse physical health problems are a result of the mental disorder, or the treatment for it," said lead investigator Benjamin Perry, PhD, of the University of Cambridge Department of Psychiatry, 

. "In essence, the received wisdom is that the mental disorder comes first. But we've found that this isn't necessarily the case, and for some individuals, it may be the other way around, suggesting that physical health problems detectable from childhood might be risk factors for adult psychosis and depression."

To explore how developmental trajectories of fasting insulin levels and BMI during early life were associated with risks for psychosis and depression later in life, investigators designed their study as an analysis of data from within ALSPAC. A birth cohort study enrolling ALSPAC enrolled more than 14,000 live births born between April 1, 1991 and December 31, 1992.

During ALSPAC, measurements of fasting insulin levels were recorded at ages 9, 15, 18, and 24 years. A total of 5790 participants had data related to fasting insulin levels and were included in the analyses. BMI measurements were recorded at 1, 2, 3, 4, 7, 9, 10, 11, 12, 15, 18, and 24 years. A total of 10,463 participants had data available for BMI. Using the data from the aforementioned patient groups, investigators created 3 distinct trajectories for fasting insulin levels and 5 distinct trajectories for BMI.

For the purpose of analysis, investigators used data related to sex, race/ethnicity, paternal social class, childhood emotional and behavioral problems, and cumulative scores of sleep problems, average calorie intake, physical activity, smoking, and alcohol and substance use in childhood and adolescence as confounders in adjusted analyses. The primary outcomes of interest were psychosis risk and depression risk at 24 years. Of note, psychosis risk was defined by psychotic experiences, psychotic disorder, at-risk mental state status, and negative symptom score while depression risk was measured using the computerized Clinical Interview Schedule-Revised.

Upon analysis, investigators found individuals with persistently high fasting insulin levels were associated with a psychosis at-risk mental state (aOR, 5.01; 95% CI, 1.76-13.19) and psychotic disorders (aOR, 3.22; 95% CI, 1.11-9.90), but not depression (aOR, 1.98; 95% CI, 0.56-7.79). When assessing BMI trajectories, results indicated a puberty-onset major increase in BMI as associated with an increased risk of depression (aOR, 4.46; 95% CI, 2.38-9.87) but not psychosis (aOR, 1.98; 95% CI, 0.56-7.79).

"These findings are an important reminder that all young people presenting with mental health problems should be offered a full and comprehensive assessment of their physical health in tandem with their mental health," added Perry. "Intervening early is the best way to reduce the mortality gap sadly faced by people with mental disorders like depression and psychosis.”

Longitudinal Trends in Childhood Insulin Levels and Body Mass Index and Associations With Risks of Psychosis and Depression in Young Adults

Articles

An analysis of children from the Avon Longitudinal Study of Parents and Children is providing insight into the potential for increased risk of mental health disorders among patients with high insulin levels or high BMI trajectory as a child. 

Insulin Levels, BMI Trajectory Help Predict Risk of Mental Health Disorders Later in Life

Insights from a systematic review and meta-analysis of published and unpublished trial data provide clinicians with an overview of the safety and efficacy of low and very-low carbohydrate diets for remission of 

Results of the analyses, which included data from nearly two dozen randomized trials, suggest pati3nts adhering to a low carbohydrate diet for 6 months could lead to remission of diabetes without increasing risk for adverse events, but investigators also noted this association appeared to fade at the 12-month mark.

“Moderate to low certainty evidence suggests that patients adhering to LCDs for six months may experience greater rates of remission of diabetes without adverse consequences compared with other diets commonly recommended for management of type 2 diabetes (for example, low fat diets),” wrote study investigators.

With an interest in developing a greater understanding of how specific diets influence development and remission of diabetes, a team led by investigators from the Department of Nutrition at Texas A&M University designed the current study as a meta-analysis and systematic review of trials of the CENTRAL, Medline, Embase, CINAHL, CAB, and grey literature sources from inception through August 25, 2020. For the current study, investigators hoped to include all randomized clinical trials evaluation low carbohydrate diets and very low carbohydrate diets for at least 12 weeks in patients with type 2 diabetes.

For the purpose of analysis, low carbohydrate diets were defined as fewer than 130 grams per day or less than 26% of a 2000 kilocalorie per day diet and very low carbohydrate diets were defined as less than 10% of calories from carbohydrates. The primary outcomes of interest were the remission of diabetes, weight loss, HbA1c, fasting glucose, and adverse events. Investigators defined remission of diabetes as an HbA1c less than 6.5% or a fasting glucose of less than 7.0 mmol/L. Secondary outcomes of interest included health-related quality of life and biochemical laboratory data. All outcomes were indecently screened, exacted, and assessed for risk of bias and GRADE certainty of evidence at 6 and 12 months of follow-up.

The investigators’ search returned 15,759 citations, which resulted ini the identification of 23 trials for inclusion in their systematic review and meta-analysis. These 23 trials included 1357 participants and 40.6% of outcomes within these trials were judged to be at low risk of bias.

When assessing outcomes at 6 months, low carbohydrate diets were associated with higher rates of diabetes remission than control diets (Risk Difference, 0.32; 95% CI, 0.17-0.47; 8 studies, n=264, I2=58%). Investigators pointed out a smaller, non-significant association was found when assessing remission without medication use.

When assessing outcomes at 12 months, investigators noted data on remission was sparse and observed effects on remission were small or indicated trivial increase in risk of diabetes. Investigators pointed out large improvements were seen when examining weightless, triglycerides, and insulin sensitivity at 6 months, but these effects declined when assessed at 12 months. In an analysis of subgroup assessments, investigators determined very low carbohydrate diets were less effective than low carbohydrate diets for weight loss at 6 months, but noted this effect was explained by diet adherence.

“Considering this and a recent systematic review of cohort studies suggesting that long term LCDs are associated with increased mortality, clinicians might consider short term LCDs for management of type 2 diabetes, while actively monitoring and adjusting diabetes medication as needed,” wrote investigators.

Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data

A systematic review and meta-analysis of 23 trials suggest adhering to a low carbohydrate diet for a 6-month period could facilitate remission of diabetes and lead to reductions in body weight. 

Study Suggests Short-Term Low Carb Diet Could Induce Diabetes Remission

Questionnaires from more than 400 patients with 

 are offering clinicians further insight into how the ongoing pandemic has impacted diabetics in regard to glycemic control, body weight, and stress levels.

Results of the study describe a situation where diabetics have experienced increases in stress, anxiety, and body weight, but no deterioration of glycemic control in patients with type 1 and type 2 diabetes during lockdown periods.

“We show that in people with relatively well controlled type 1 and type 2 diabetes the COVID-19 pandemic and lockdown measures increased stress and resulted in weight gain and less physical exercise during this short observational period. However, despite these factors no deterioration in glycemic control was observed,” wrote investigators.

To learn more about the effects of lockdown measures on various aspects of diabetes management, investigators from Leiden University Medical Center designed the current study as a short-term observational cohort study of patients treated at the outpatient diabetes clinic at the medical center. For inclusion in the study, patients needed to be at least 18 years of age and be sufficient enough in Dutch to perform fingerpicks and complete an online questionnaire.

Of note, patients were excluded if they were pregnant, diagnosed with a malignancy within the previous 6 months, were receiving immunotherapy or chemotherapy, or were admitted to a hospital or rehabilitation center. In total, 435 people were identified for inclusion in the current study—280 with type 1 diabetes and 155 with type 2 diabetes.

Of the 435 patients included in the study, 76.8% were using a basal-bolus regimen and 8.3% were using basal insulin only. In comparison to their counterparts with type 1 diabetes, patients with type 2 diabetes were on average 12.3 years older and had a higher BMI. Of the 435 included in the study, 399 completed the questionnaire on daily routines, physical activity, psychological stress, glycemic control, and medication use. For the purpose of analysis, HbA1c measurements during the lockdown were compared with the last known HbA1c prior to lockdown.

During the lockdown, 34.1% of respondents reported elevated stress—33.6% of type 1 diabetics and 35.1% of type 2 diabetics. Additionally, 27.3% of all participants reported increased levels of anxiety—27.5% of type 1 diabetics and 26.9% of type 2 diabetics. In analyses, changes in perceived stress was associated with a change in HbA1c (95% CI, 0.015-0.38; 

=.034) but changes in anxiety levels were not associated with changes in HbA1c.

When assessing exercise and weight gain, investigators found 40.9% of patients reported weight gain and 45.7% reported getting less exercise during the pandemic. Investigators noted 12% of respondents reported losing weight and 10% reported more exercise. In an analysis, change in exercise or weight gain was not associated with changes in HbA1c.

In regard to glycemic control, there was improvements among those in the highest HbA1c tertile in both type 1 (-0.39% [-4.3 mmol/mol], 

 <.0001) and type 2 (-0.62% [-6.8 mmol/mol], 

=.0036) diabetics. Further analysis indicated time in range was higher (60.5% vs 63.4%; 

=.0009) and time above range was lower (34.6% vs 32.1%; 

 <.003) during the lockdown period than in the pre-lockdown period for the entire study cohort.

“Our short-term observational study shows that lockdown measures resulted in increased levels of perceived stress, weight gain and less exercise in both people with relatively well-controlled type 1 and type 2 diabetes, however this did not negatively impact glycemic control,” wrote investigators.

Increased stress, weight gain and less exercise in relation to glycemic control in people with type 1 and type 2 diabetes during the COVID-19 pandemic

An analysis of data from questionnaires sent to more than 400 patients from a diabetes clinic in Europe gives insight into the impact of lockdown measures on body weight, HbA1c control, and perceived levels of stress and anxiety. 

Lockdowns Led to Increases in Weight, Anxiety But Improved Glucose Control in Diabetes Patients

Research from a team at the University of Sheffield and Sheffield Teaching Hospitals suggests use of denosumab could drastically reduce the number of revision procedures following hip replacements.

Results of the study indicate use of the osteoporosis therapy could help prevent the incidence of osteolysis and was able to eliminate approximately 90% of the cells responsible for bone loss in patients who were scheduled to have revision hip surgery.

"For decades scientists have been looking for a therapy that will help to protect vulnerable areas of bone and prevent revision surgery which not only has huge cost implications for the NHS, but also causes pain and reduces mobility for patients," said Mark Wilkinson, MBChB, PhD, a professor in the University of Sheffield's Department of Oncology and Metabolism, 

. "This study is a significant breakthrough as we've demonstrated there is a drug, already available and successful in the treatment of osteoporosis, which has the potential to prevent up to half of all revised replacement surgeries which are caused by osteolysis.”

With revision surgery posing a serious risk to patients and creating an additional cost burden, Wilkinson and a team of colleagues set out to establish whether any existing therapies could mitigate the impact of osteolysis in a clinical trial. The current study was designed as a phase 2 trial examining use of the human monoclonal antibody denosumab on osteolytic lesion activity in patients undergoing revision total hip arthroplasty surgery.

For their double-blind, placebo-controlled, proof of concept superiority trial, investigators enrolled patients aged 30 years and older and scheduled for revision surgery for symptomatic, radiographically confirmed osteolysis. These patients were randomized in a 1:1 ratio to subcutaneous denosumab at a 60 mg dose or placebo therapy. The primary outcome of the trial was the between-group difference in osteoclast number per millimeter of bone surface of biopsies taken from the osteolytic membrane–bone interface at surgery 8 weeks later, which was measured using quantitative histomorphometry in all patients who underwent revision surgery.

From December 12, 2012 through June 24, 2018, investigators assessed 51 patients for eligibility and 24 were ultimately included in the study. Investigators noted 2 of the 24 patients had their revision surgery cancelled for unrelated reasons and 22 patients were included in the final analyses. Of the 22 included, 12 were randomized to placebo therapy and 10 were assigned to the denosumab group. Of note, exclusion criteria for the study included currently using or having a history of using oral bisphosphonate, having an eGFR less than 30, and being pregnant or breast feeding, among others.

Upon analysis, results indicated there were 83% fewer osteoclasts at the osteolysis membrane-bone interface in the denosumab group compared to the placebo group (median, 0.05 per mm [IQR, 0.11] vs 0.30 mm [0.40]; 

=.011). There were no deaths or treatment-related serious adverse events observed during the study. Overall, 7 adverse events, including one severe adverse events, occurred among 4 of the 11 patients randomized to denosumab. Among those in the placebo arm, 10 adverse events, including 3 severe adverse events, occurred in 5 of 13 patients randomized to placebo therapy.

"It is very clear from our bone biopsies and bone imaging that the injection stops the bone absorbing the micro-plastic particles from the replacement joint and therefore could prevent the bone from being eaten away and the need for revision surgery,” Wilkinson added.

Effect of denosumab on osteolytic lesion activity after total hip arthroplasty: a single-centre, randomised, double-blind, placebo-controlled, proof of concept trial,

A phase 2 trial from investigators in the UK suggests use of denosumab, a human monoclonal antibody, could drastically reduce the rate of revision procedures after hip replacements. 

Patrick Campbell

Articles

Insulin Levels, BMI Trajectory Help Predict Risk of Mental Health Disorders Later in Life

Study Suggests Short-Term Low Carb Diet Could Induce Diabetes Remission

Lockdowns Led to Increases in Weight, Anxiety But Improved Glucose Control in Diabetes Patients

Osteoporosis Therapy Could Cut Need for Revision Procedures Following Hip Replacements