Prevalence and predictors of diabetes distress and depression in people with type 1 diabetes.

Background: People living with diabetes often encounter psychosocial challenges, including diabetes distress and depression. Despite this, little research has focused on the co-occurrence of these conditions. This study aimed to explore the prevalence of depressive symptoms and diabetes distress in people with type 1 diabetes in Kuwait and to identify clinical and demographic factors associated with these conditions. Methods: A total of 832 people with type 1 diabetes (females: 54.1%, mean age: 29 ± 8.5 years), were invited to participate in Dose Adjustment for Normal Eating (DAFNE) course. Diabetes distress was measured using the Problem Areas in Diabetes (PAID) scale and depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9). Depressive symptoms were defined as PHQ-9 scores ≥10. Data on biomedical outcomes, lifestyle factors, and sociodemographic information were collected. Results: The prevalence rates of diabetes distress and depressive symptoms were 27.8% and 38.3%, respectively. Notably, 19.6% of people experienced both conditions. In the regression analysis, PAID scale and PHQ-9 scores were significantly associated, patients with higher score on depressive symptoms scale were more likely to suffer diabetes distress (B= 2.65, p < 0.001). Female sex (odds ratio [OR]= 2.2, 95% CI= 1.5, 3.2), higher hemoglobin A1c levels (OR= 1.6, 95% CI= 1.0, 2.5), obesity (OR= 1.7, 95% CI= 1.1, 2.8), inactivity (OR= 2.4, 95% CI= 1.6, 3.6), microvascular complications (OR= 2.8, 95% CI= 1.5, 5.4), and lipohypertrophy (OR= 1.7, 95% CI= 1.1, 2.5) were associated with greater odds for the co-occurrence of diabetes distress and depressive symptoms (p< 0.05 for all). Conclusion: The majority of people with type 1 diabetes in Kuwait experience both diabetes distress and depressive symptoms. The strong correlation between diabetes distress and depressive symptoms suggests mutual predictability. The co-occurrence of both symptoms is associated with many sociodemographic and clinical factors.

Obesity Treatments to Improve Type 1 Diabetes (OTID): a randomized controlled trial of the combination of glucagon-like peptide 1 analogues and sodium-glucose cotransporter 2 inhibitors-protocol for Obesity Treatments to Improve Type 1 Diabetes (the OTID trial).

BACKGROUND: The guidelines of the American Diabetes Association and European Association for the Study of Diabetes suggest that patients with obesity type 2 diabetics and chronic kidney disease need either glucagon-like peptide 1 receptor analogues or sodium-glucose cotransporter-2 inhibitors. If neither achieve metabolic control, then the recommendation is to combine both drugs. The evidence base for combining glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors is not well researched, and hence, the impact of the guidelines is limited. The aim of this randomized controlled trial is to test the impact of the combination of glucagon-like peptide 1 receptor analogues/sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage, in patients with type 1 diabetes and chronic kidney disease. In addition, we will explore the associated changes in the metabolic pathways with each of the treatments used in this randomized controlled trial. METHODS: In this 6-month randomized control trial, 60 participants aged between 21 and 65 years, with a body mass index above 25 kg/m2, and type 1 diabetics with chronic kidney disease will be randomized to receive 1 of 5 possible treatments: (1) standard care (control), (2) glucagon-like peptide 1 receptor analogues alone, (3) sodium-glucose cotransporter-2 inhibitors alone, (4) combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors and (5) combination of glucagonlike peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors with intensive lifestyle advice. The primary objective will be the percentage change in total body weight from baseline at 6 months. The secondary objectives are to compare the change in glycaemia; blood pressure; dyslipidaemia; albuminuria; proportion of participants reaching weight loss of ≥ 5%, ≥ 10% and ≥ 15%; and change in BMI (kg/m2) from baseline and change in waist circumference (cm). All the experiments will be conducted at the Dasman Diabetes Institute after approval from the local research and ethics committee. DISCUSSION: The present randomized controlled trial aims to investigate the impact of the combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage in patients with type 1 diabetes mellitus and chronic kidney disease, as well as exploring the associated changes in the metabolic pathways with each of the treatments used. This study addresses the current gap in the evidence base regarding the combination of these two drugs, which is particularly relevant given the American Diabetes Association and European Association for the Study of Diabetes guidelines recommending their combined use for patients with obesity, type 2 diabetes, and chronic kidney disease who do not achieve metabolic control with either drug alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05390307 Trial registration date - 25th May 2022.

The emergence of obesity in type 1 diabetes.

Obesity, a chronic low-grade inflammatory disease represented by multifactorial metabolic dysfunctions, is a significant global health threat for adults and children. The once-held belief that type 1 diabetes is a disease of people who are lean no longer holds. The mounting epidemiological data now establishes the connection between type 1 diabetes and the subsequent development of obesity, or vice versa. Beyond the consequences of the influx of an obesogenic environment, type 1 diabetes-specific biopsychosocial burden further exacerbates obesity. In the course of obesity management discussions, recurring challenges surfaced. The interplay between weight gain and escalating insulin dependence creates a vicious cycle from which patients struggle to break free. In the absence of weight management guidelines and regulatory approval for this population, healthcare professionals must navigate the delicate balance between benefits and risks. The gravity of this circumstance highlights the importance of bringing these topics to the forefront. In this Review, we discuss the changing trends and the biopsychosocial aspects of the intersection between type 1 diabetes and obesity. We highlight the evidence supporting the therapeutic means (i.e., exercise therapy, nutritional therapy, adjunct pharmacotherapy, and bariatric surgery) and directions for establishing a more robust and safer evidence-based approach.

Optimizing an mHealth Program to Promote Type 2 Diabetes Prevention in High-Risk Individuals: Cross-Sectional Questionnaire Study.

BACKGROUND: We evaluated the outcomes of a pilot SMS text messaging-based public health campaign that identified social networking nodes and variations of response rates to develop a list of variables that could be used to analyze and develop an outreach strategy that would maximize the impact of future public health campaigns planned for Kuwait. Computational analysis of connections has been used to analyze the spread of infectious diseases, dissemination of new thoughts and ideas, efficiency of logistics networks, and even public health care campaigns. Percolation theory network analysis provides a mathematical alternative to more established heuristic approaches that have been used to optimize network development. We report on a pilot study designed to identify and treat subjects at high risk of developing type 2 diabetes mellitus in Kuwait. OBJECTIVE: The aim of this study was to identify ways to optimize efficient deployment of resources and improve response rates in a public health campaign by using variables identified in this secondary analysis of our previously published data (Alqabandi et al, 2020). This analysis identified key variables that could be used in a computational analysis to plan for future public health campaigns. METHODS: SMS text message screening posts were sent inviting recipients to answer 6 questions to determine their risk of developing type 2 diabetes mellitus. If subjects agreed to participate, a link to the Centers for Disease Control and Prevention prediabetes screening test was automatically transmitted to their mobile devices. The phone numbers used in this campaign were recorded and compared to the responses received through SMS text messaging and social media forwarding. RESULTS: A total of 180,000 SMS text messages through 5 different campaigns were sent to 6% of the adult population in Kuwait. A total of 260 individuals agreed to participate, of which 153 (58.8%) completed the screening. Remarkably, 367 additional surveys were received from individuals who were not invited by the original circulated SMS text messages. These individuals were invited through forwarded surveys from the original recipients after authentication with the study center. The original SMS text messages were found to successfully identify influencers in existing social networks to improve the efficacy of the public health campaign. CONCLUSIONS: SMS text messaging-based health care screening campaigns were found to have limited effectiveness alone; however, the increased reach through shared second-party forwarding suggests the potential of exponentially expanding the reach of the study and identifying a higher percentage of eligible candidates through the use of percolation theory. Future research should be directed toward designing SMS text messaging campaigns that support a combination of SMS text message invitations and social networks along with identification of influential nodes and key variables, which are likely unique to the environment and cultural background of the population, using percolation theory modeling and chatbots.

Corrigendum: A comparison of physical activity, muscle strength, and sleep between people with type 2 diabetes in Kuwait and he UK: a cross sectional study.

[This corrects the article DOI: 10.3389/fendo.2022.1067227.].

Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a complicated condition related to type 2 diabetes mellitus (T2D). ANGPTL8 is a hepatic protein highlighted as a risk factor for DN in patients with T2D; additionally, recent evidence from DN studies supports the involvement of growth hormone/IGF/IGF-binding protein axis constituents. The potential link between ANGPTL8 and IGFBPs in DN has not been explored before. Here, we assessed changes in the circulating ANGPTL8 levels in patients with DN and its association with IGFBP-1, -3, and -4. Our data revealed a significant rise in circulating ANGPTL8 in people with DN, 4443.35 ± 396 ng/mL compared to 2059.73 ± 216 ng/mL in people with T2D (p < 0.001). Similarly, levels of IGFBP-3 and -4 were significantly higher in people with DN compared to the T2D group. Interestingly, the rise in ANGPTL8 levels correlated positively with IGFBP-4 levels in T2DM patients with DN (p < 0.001) and this significant correlation disappeared in T2DM patients without DN. It also correlated positively with serum creatinine and negatively with the estimated glomerular filtration rate (eGFR, All < 0.05). The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and IGFBP4 was 0.76 (0.69-0.84), p < 0.001, and the specificity was 85.9%. In conclusion, our results showed a significant increase in ANGPTL8 in patients with DN that correlated exclusively with IGFBP-4, implicating a potential role of both proteins in the pathophysiology of DN. Our findings highlight the significance of these biomarkers, suggesting them as promising diagnostic molecules for the detection of diabetic nephropathy.

The effect of timing of remotely supervised exercise on glucose control in people with type 1 diabetes during Ramadan: A randomised crossover study.

AIM: The aim of the current study was to compare glucose responses when remotely supervised exercise was performed before or after breaking the fast, during Ramadan, in people with type 1 diabetes. METHODS: People with type 1 diabetes were recruited to this randomised cross over design study, which took place in Kuwait during Ramadan in 2021-2022. Interstitial glucose was measured using continuous glucose monitors during a baseline week of normal activity and during weeks where remotely supervised exercise was performed, three times per week, either before (afternoon) or after (evening) breaking the fast, in a randomised crossover design. Exercise involved resistance and aerobic exercise and was supervised during a video call. RESULTS: Thirty-two participants were recruited to the study (age 34(9) years and BMI 26(4)kg/m2). Mean interstitial glucose levels were lower on exercise days, compared to equivalent days in the baseline week, during both afternoon (8.6(1.8) mmol/L vs 9.1(1.4) mmol/L, p = 0.035) and evening (8.7(1.8) mmol/L vs 9.6(1.8) mmol/L, p < 0.001) exercise weeks. Mean glucose levels were lower the day after exercise, relative to both baseline (p < 0.001) and exercise (p = 0.011) days, in the evening exercise week only. CONCLUSIONS: Remotely supervised exercise performed during Ramadan can safely reduce interstitial glucose levels and may be of greater benefit when performed in the evening, further work is required to confirm this in a larger trial.

Association between alleles, haplotypes, and amino acid variations in HLA class II genes and type 1 diabetes in Kuwaiti children.

Type 1 diabetes (T1D) is a complex autoimmune disorder that is highly prevalent globally. The interactions between genetic and environmental factors may trigger T1D in susceptible individuals. HLA genes play a significant role in T1D pathogenesis, and specific haplotypes are associated with an increased risk of developing the disease. Identifying risk haplotypes can greatly improve the genetic scoring for early diagnosis of T1D in difficult to rank subgroups. This study employed next-generation sequencing to evaluate the association between HLA class II alleles, haplotypes, and amino acids and T1D, by recruiting 95 children with T1D and 150 controls in the Kuwaiti population. Significant associations were identified for alleles at the HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci, including DRB1*03:01:01, DQA1*05:01:01, and DQB1*02:01:01, which conferred high risk, and DRB1*11:04:01, DQA1*05:05:01, and DQB1*03:01:01, which were protective. The DRB1*03:01:01~DQA1*05:01:01~DQB1*02:01:01 haplotype was most strongly associated with the risk of developing T1D, while DRB1*11:04-DQA1*05:05-DQB1*03:01 was the only haplotype that rendered protection against T1D. We also identified 66 amino acid positions across the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes that were significantly associated with T1D, including novel associations. These results validate and extend our knowledge on the associations between HLA genes and T1D in Kuwaiti children. The identified risk alleles, haplotypes, and amino acid variations may influence disease development through effects on HLA structure and function and may allow early intervention via population-based screening efforts.

The effect of home-based resistance exercise training in people with type 2 diabetes: A randomized controlled trial.

AIMS: To evaluate the effects of pragmatic home-based resistance exercise training on glycated haemoglobin (HbA1c) as well as muscle strength and body composition in people with type 2 diabetes. MATERIALS AND METHODS: People with type 2 diabetes were randomized (1:1) to usual care or usual care plus home-based resistance exercise for 32 weeks. The changes in HbA1c, body composition, physical function, quality of life, continuous glucose monitoring and liver fat were compared by randomized group using linear regression. RESULTS: This study recruited 120 participants (female: n = 46 [38%], age 60.2 (9.4) years, BMI 31.1 (5.4) kg.m-2 ), 64 to intervention and 56 to usual care. Intention to treat analysis revealed no effect on HbA1c (difference in difference: -0.4 mmol/mol, 95% confidence interval [CI]: -3.26, 2.47; p = 0.78) but the intervention increased the number of push-ups (3.6 push-ups, 95% CI: 0.8, 6.4), arm lean mass (116 g, 95% CI: 6, 227) and leg lean mass (438 g, 95% CI 65, 810) and decreased liver fat (-1.27%, 95% CI -2.17, -0.38), with no differences in other outcomes. Per-protocol analysis revealed similar results. CONCLUSIONS: Home-based resistance exercise is unlikely to lower HbA1c in people with type 2 diabetes but may be of benefit for maintaining muscle mass and function and reducing liver fat.

Are we ready for the next pandemic? Lessons learned from healthcare professionals' perspectives during the COVID-19 pandemic.

Background: The mental health and wellbeing of people watching the Corona Virus Disease 2019 (COVID-19) pandemic unfold has been discussed widely, with many experiencing feelings of anxiety and depression. The state of mental health of medical staff on the frontlines providing care should be examined; medical staff are overworked to meet the demands of providing care to the rise in cases and deterioration in capacity to meet demands, and this has put them under great psychological pressure. This may lead to an increase in medical errors, affect quality of care, and reduce staff retention rates. Understanding the impact the pandemic has had on healthcare professionals is needed to provide recommendations to prepare for future crises. Objectives: To be able to meet the needs of the medical workforce on the frontlines and inform psychological support interventions and strategies for future pandemics, we aim to identify and explore the psychological impact of COVID-19 in Kuwait on healthcare professionals in close contact with patients. Methods: Using semi-structured interviews, we conducted interviews between February and July 2021 with 20 healthcare professionals across Ministry of Health hospitals who were part of COVID teams. Interviews were transcribed verbatim, and analysis was conducted using principles of thematic framework analysis. Results: Three themes emerged to help prepare future healthcare frontline workers on an individual, organizational, and national level: enhance self-resilience, a better-equipped workforce and healthcare environment, and mitigate stigma and increase public awareness. Conclusion: The results have assisted in highlighting areas of improvement to support the healthcare workforce in the current environment, as well as better prepare them for future pandemics. The findings have also provided insight to recommend targeted interventions. These should improve the psychological wellbeing and help in supporting healthcare professionals to reduce burnout, continue effective care of patients, and enhance resilience.

Effect of COVID-19 vaccine on blood glucose metrics in Arabic people with type 1 diabetes.

Introduction: People with diabetes are at a higher risk for coronavirus disease-19 (COVID-19) and hence are prioritized for vaccination. The aim of the current study was to investigate the effects of COVID-19 vaccination on blood glucose control in Arabic people with type 1 diabetes (T1D). Secondary aim was to compare the responses between the two vaccines approved for use in Kuwait. Method: This retrospective study compared ambulatory glucose metrics, using a continuous glucose monitoring device, measured for 14 days before, and 7 days and 14 days after, the first and second dose of the COVID-19 vaccine in Arabic people with Type 1 diabetes (T1D). We also explored possible links with vaccine type and other clinical characteristics. Glucose metrics calculated were time in range (TIR, 3.9-10 mmol/L), time above range (TAR, 10.1- 13.9 mmol/L or >13.9 mmol/L), time below range (TBR, 3- 3.9 mmol/L or <3 mmol/L) and glucose variability (CV). Results: We enrolled 223 participants in the study. Over the 7 days period after the first vaccination dose there was a decrease in TIR (mean difference (SD) -1.9% ± 14.8%; p = 0.05) and increase in TAR >10 mmol/L (2.2% ± 15.9%; p = 0.04), with no effects on TBR. These effects were not seen after the second dose or 14 days after either dose. There was a decrease in CV over the 7 days period after the first (-1.2% ± 7.4%; p = 0.02) and second vaccine doses (-1.1% ± 6.9%; p = 0.03), with no effects noted 14 days after either dose. In subgroup analysis similar effects on TIR and TAR were also seen in those who had received the viral vector-based vaccine, but not the mRNA-based vaccine, although the decrease in CV was seen in those who had received the mRNA based vaccine but not the viral vector-based vaccine. Conclusion: We found a temporary impairment in glucose control in the first 7 days, particularly among individuals receiving viral vector vaccines. The group receiving mRNA vaccine was likely to experience an increase in glucose levels above the target range. However, the temporary change in metrics appears to return to pre-vaccination levels after one-week post-vaccination. The effects on glycemic parameters were more neutral after the second dose.

Plasma insulin is required for the increase in plasma angiopoietin-like protein 8 in response to nutrient ingestion.

BACKGROUND: Plasma levels of angiopoietin-like protein 8 (ANGPTL8) are regulated by feeding and they increase following glucose ingestion. Because both plasma glucose and insulin increase following food ingestion, we aimed to determine whether the increase in plasma insulin and glucose or both are responsible for the increase in ANGPTL8 levels. METHODS: ANGPTL8 levels were measured in 30 subjects, 14 with impaired fasting glucose (IFG), and 16 with normal fasting glucose (NFG); the subjects received 75g glucose oral Glucose tolerance test (OGTT), multistep euglycaemic hyperinsulinemic clamp and hyperglycaemic clamp with pancreatic clamp. RESULTS: Subjects with IFG had significantly higher ANGPTL8 than NGT subjects during the fasting state (p < 0.05). During the OGTT, plasma ANGPTL8 concentration increased by 62% above the fasting level (p < 0.0001), and the increase above fasting in ANGPTL8 levels was similar in NFG and IFG individuals. During the multistep insulin clamp, there was a dose-dependent increase in plasma ANGPTL8 concentration. During the 2-step hyperglycaemic clamp, the rise in plasma glucose concentration failed to cause any change in the plasma ANGPTL8 concentration from baseline. CONCLUSIONS: In response to nutrient ingestion, ANGPTL8 level increased due to increased plasma insulin concentration, not to the rise in plasma glucose. The incremental increase above baseline in plasma ANGLPTL8 during OGTT was comparable between people with normal glucose tolerance and IFG.

Association Between Depression, Diabetes Self-Care Activity and Glycemic Control in an Arab Population with Type 2 Diabetes.

Purpose: Poor self-care behavior and depression are associated with worse glycemic control, but the relationship between these variables is poorly reported. The present study aimed to describe self-care behaviors and explore the association between depression, self-care and glycemic control in people with type 2 diabetes in an Arab population. Patients and Methods: This study recruited 446 patients with type-2 diabetes from an outpatient clinic in Kuwait and completed assessments of diabetes self-care using the Summary of Diabetes Self-Care Activities (SDSCA) questionnaire and depression using the Patients Health Questionnaire-9 (PHQ-9) scales. Multiple linear regression models were used to determine the associations between depression, self-care behaviors and glycemic control. Results: Self-care behaviors were highest for medication taking (92.9%), an average for foot care (61.4%), blood glucose testing (60%) and healthy diet (55.7%), and lowest for exercise (27.1%). Depression, poor self-care activities and poor HbA1c levels were inter-correlated in univariate analysis (p< 0.03). In regression analysis, following healthful eating (B= -0.27, p< 0.001), general eating plan (B= -0.21, p= 0.01), more space carbohydrates evenly throughout the day (B= - 0.17, p= 0.03) and exercise at least 30 minutes (B= -0.17, p= 0.02) behaviors were associated with better HbA1c levels. However, depression was associated with poor scores of following a general eating plan (B= -0.20, p= 0.03), space carbohydrates evenly throughout the day (B= -0.21, p= 0.05), and exercising at least 30 minutes (B= -0.24, p= 0.03) behaviors. Depression scores were also associated with poor HbA1c levels (B= 0.32, p= 0.03). However, this association no longer persists after mutual adjustment with following a healthy diet (B= 0.14, p= 0.38) and exercise (B = 0.26, p = 0.08) behaviors. Conclusion: Self-care activity was less than fifty percent in people with type 2 diabetes and higher activity was associated with better glycemic control. However, depression adversely affects self-care behaviors. To maintain and achieve glycemic control, diabetes educators might motivate people with type 2 diabetes to enhance their self-care activities, particularly those with depression symptoms and poor compliance with self-care activities.

Glucagon-like peptide-1 agonists combined with sodium-glucose cotransporter-2 inhibitors reduce weight in type 1 diabetes.

OBJECTIVE: This study evaluated whether adding sodium-glucose cotransporter-2 inhibitors (SGLT2i) and/or glucagon-like peptide-1 receptor agonists (GLP1-RA) to insulin reduced weight and glycemia in people with type 1 diabetes. METHODS: This retrospective analysis of electronic health records evaluated 296 people with type 1 diabetes over 12 months after medications were first prescribed. Four groups were defined: control n = 80, SGLT2i n = 94, GLP1-RA n = 82, and combination of drugs (Combo) n = 40. We measured changes at 1 year in weight and glycated hemoglobin (HbA1c). RESULTS: The control group did not have changes in weight or glycemic control. The mean (SD) percentage weight loss after 12 months was 4.4% (6.0%), 8.2%  (8.5%), and 9.0% (8.4%) in the SGLT2i, GLP1-RA, and Combo groups, respectively (p < 0.001). The Combo group lost the most weight (p < 0.001). The HbA1c reduction was 0.4% (0.7%), 0.3% (0.7%), and 0.6% (0.8%) in the SGLT2i, GLP1-RA, and Combo groups, respectively (p < 0.001). The Combo group had the biggest improvements in glycemic control and total and low-density lipoprotein cholesterol compared with baseline (all p < 0.01). Severe adverse events were similar between all the groups, with no increased risk of diabetic ketoacidosis. CONCLUSIONS: The SGLT2i and GLP1-RA agents on their own improved body weight and glycemia, but combining the medications resulted in more weight loss. Treatment intensification appears to result in benefits with no difference in severe adverse events.

Metabolic and Vascular Risk Factor Variability Over 25 Years Relates to Midlife Brain Volume and Cognition.

BACKGROUND: Metabolic and vascular risk factors (MVRF) are associated with neurodegeneration and poor cognition. There is a need to better understand the impact of these risk factors on brain health in the decades that precede cognitive impairment. Longitudinal assessments can provide new insight regarding changes in MVRFs that are related to brain imaging features. OBJECTIVE: To investigate whether longitudinal changes in MVRF spanning up to 25 years would be associated with midlife brain volume and cognition. METHODS: Participants were from the CARDIA study (N = 467, age at year 25 = 50.6±3.4, female/male = 232/235, black/white = 161/306). Three models were developed, each designed to capture change over time; however, we were primarily interested in the average real variability (ARV) as a means of quantifying MVRF variability across all available assessments. RESULTS: Multivariate partial least squares that used ARV metrics identified two significant latent variables (partial correlations ranged between 0.1 and 0.26, p < 0.01) that related MVRF ARV and regional brain volumes. Both latent variables reflected associations between brain volume and MVRF ARV in obesity, cholesterol, blood pressure, and glucose. Subsequent bivariate correlations revealed associations among MVRF factors, aggregate brain volume and cognition. CONCLUSION: This study demonstrates that MVRF variability over time is associated with midlife brain volume in regions that are relevant to later-life cognitive decline.

A randomised crossover trial: Exploring the dose-response effect of carbohydrate restriction on glycaemia in people with well-controlled type 2 diabetes.

BACKGROUND: Trials investigating the role of carbohydrate restriction in the management of glycaemia in type 2 diabetes (T2D) have been confounded by multiple factors, including degree of calorie restriction and dietary protein content, as well as by no clear definition of a low-carbohydrate diet. The present study aimed to provide insight into the relationship between carbohydrate restriction and glycaemia by testing the effect of varying doses of carbohydrate on continuous glucose concentrations within a range of intakes defined as low-carbohydrate at the same time as controlling for confounding factors. METHODS: This was a randomised crossover trial in participants with T2D (HbA1c: 6.6 ± 0.6%, 49 ± 0.9 mmol mol-1 ) testing five different 6-day eucaloric dietary treatments with varying carbohydrate content (10%, 15%, 20%, 25%, and 30% kcal). Diets exchanged %kcal from carbohydrate with fat, keeping protein constant at 15% kcal. Daily self-weighing was employed to ensure weight stability throughout each treatment arm. Between dietary treatments, participants underwent a washout period of at least 7 days and were advised to maintain their habitual diet. Glycaemic control was assessed using a continuous glucose monitoring device. RESULTS: Twelve participants completed the study. There were no differences in 24-h and post-prandial sensor glucose concentrations between the 30 and 10%kcal doses (7.4 ± 1.1 mmol L-1 vs. 7.6 ± 1.3 mmol L-1 [p = 0.28] and 8.1 ± 1.5 mmol L-1 vs. 8.5 ± 1.4 mmol L-1 [p = 0.28], respectively). In our exploratory analyses, we did not find any dose-response relationship between carbohydrate intake and glycaemia. A small amount of weight loss occurred in each treatment arm (range: 0.4-1.1 kg over the 6 days) but adjusting for these differences did not influence the primary or secondary outcomes. CONCLUSIONS: Modest changes in dietary carbohydrate content in the absence of weight loss at the same time as keeping dietary protein intake constant do not appear to influence glucose concentrations in people with well-controlled T2D. SUMMARY: This study randomised people with T2D to receive five different doses of carbohydrate from 10% to 30% of calories in random order to see what effect it had on their blood glucose.

A comparison of physical activity, muscle strength, and sleep between people with type 2 diabetes in Kuwait and the UK: A cross-sectional study.

Background: The aim of the current study was to determine the prevalence of low muscle strength and to evaluate physical activity and sleep characteristics in people with type 2 diabetes in Kuwait. Additionally, equivalent data from the UK Biobank cohort were compared. Methods: People with type 2 diabetes from the UK Biobank (n = 23,570) and Kuwaiti cohorts (n = 3,135) were included in this cross-sectional study. Self-reported sleep, physical activity, and muscle strength were compared between the cohorts, using linear and logistic regression, with adjustments for age, sex, and duration of diabetes. Results: Physical activity levels (-937 (-1,097, -851) Met-min/week: standardized B-coefficient -0.42 (-0.47, -0.37)) and grip strength (3.2 (-3.58, -2.82) kg: standardized B-coefficient (-0.29 (-0.32, -0.26)) were lower in the Kuwaiti cohort, and the odds of having short sleep (OR 1.32 (1.19,1.46), being classed as inactive (OR 8.70 (7.59, 9.98), and having muscle weakness (OR 1.88 (1.69, 2.09) were higher. These analyses were adjusted for age, sex, and duration of diabetes. Conclusions: The aim of the current study was to determine the prevalence of low muscle strength and to evaluate physical activity and sleep characteristics in people with type 2 diabetes in Kuwait. Additionally, equivalent data from the UK Biobank cohort were compared.

Fatal COVID-19 is Associated with Reduced HLA-DR, CD123 or CD11c Expression on Circulating Dendritic Cells.

Purpose: Severe coronavirus disease 2019 (COVID-19) is linked to insufficient control of viral replication and excessive inflammation driven by an unbalanced immune response. Plasmacytoid dendritic cells (pDCs) are specialized in the rapid production of interferons in response to viral infections, and can also prime and activate T-cells. Conventional DCs (cDCs) are critical for the elimination of viral infections owing to their specialized ability to prime and activate T cells. We assessed the frequency and phenotype of pDCs and cDCs in survivors and non-survivors of COVID-19. Patients and methods: Patients with COVID-19 were enrolled, and 22 were included in this study. Peripheral whole blood was obtained during the 2nd week of illness, stained with antibodies specific for lineage markers, human leukocyte antigen-DR isotype (HLA-DR), CD11c, and CD123, and analyzed by flow cytometry. Patients were followed-up during hospital admission and grouped into survivors (n=17) and non-survivors (n=5) of COVID-19. Results: The ratio of pDCs to pre-cDCs was significantly lower (P=0.0005) in non-survivors compared to survivors. The frequency of pDCs was significantly higher than cDC2-like cells (P=0.0002) and pre-cDCs (P<0.0001) in survivors but not in non-survivors. HLA-DR expression level on pDCs and cDC2-like cells was lower in non-survivors compared to survivors (P=0.02 and P=0.058, respectively), and HLA-DR was inversely correlated with disease severity rating (pDCs: r= -0.47, P=0.027; cDC2-like cells: r= -0.45, P=0.037). CD123 expression level on pDCs was significantly lower (P=0.038) in non-survivors compared to survivors, and CD123 was inversely correlated with disease severity rating (r=-0.5, P=0.016). CD11c expression level on cDC2-like cells was significantly lower (P=0.03) in non-survivors compared to survivors, and CD11c was inversely correlated with disease severity rating (r=-0.47, P=0.025). Conclusion: A lower frequency of pDCs compared to other circulating DCs, and lower expression levels of HLA-DR, CD123 or CD11c on DCs is associated with fatal COVID-19.