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.

Liver fibrosis and liver stiffness in patients with obesity and type 1 diabetes.

AIM: To compare hepatic stiffness and fat fraction in patients with obesity and type 1 diabetes (T1D) with type 2 diabetes (T2D) with a similar body mass index (BMI). METHODS: In this prospective cross-sectional study, 90 participants with T1D (BMI 30.5 ± 4.5 kg/m2; diabetes duration 20.5 ± 9.8 years; HbA1c 8.2% ± 1.4%) and 69 with T2D (BMI: 30.8 ± 4.6 kg/m2; diabetes duration: 11.7 ± 7.8 years; HbA1c: 7.3% ± 1.4%) were included. Liver fat fraction and stiffness were examined by magnetic resonance imaging and elastography, respectively. Logistic regressions were used to evaluate associations with biomedical variables. RESULTS: The mean liver stiffness score in patients with obesity and T1D was 2.2 ± 0.5 kPa, while in T2D it was 2.6 ± 0.8 kPa (P < .001). The liver fat fraction in patients with obesity and T1D was 3.7% ± 6.3%, and in T2D it was 10.6% ± 7.9% (P < .001). Metabolic dysfunction-associated steatotic liver disease (MASLD) was present in 13.3% of patients with T1D and in 69.6% of patients with T2D, whereas fibrosis was suggested in 7.8% of patients with T1D and in 27.5% of patients with T2D. Liver stiffness was four times higher in patients with T2D compared with those with T1D (odds ratio = 5.4, 95% confidence interval: 2.1-13.6, P < .001). Aspartate transaminase (AST), alanine transaminase, gamma-glutamyl transferase (GGT), triglycerides and the android-to-gynoid ratio were associated with elevated fat fraction in both cohorts. AST and GGT were associated with elevated liver stiffness in both cohorts. CONCLUSIONS: Patients with obesity and T1D had lower liver fat and liver stiffness compared with those patients with T2D, despite similar levels of BMI, a longer duration of diabetes and worse glycaemic control.

Palmitate Potentiates Lipopolysaccharide-Induced IL-6 Production via Coordinated Acetylation of H3K9/H3K18, p300, and RNA Polymerase II.

IL-6 is elevated in obese individuals and participates in the metabolic dysfunction associated with that condition. However, the mechanisms that promote IL-6 expression in obesity are incompletely understood. Because elevated levels of palmitate and LPS have been reported in obesity, we investigated whether these agents interact to potentiate IL-6 production. In this study, we report that LPS induces higher levels of IL-6 in human monocytes in the presence of palmitate. Notably, the priming effect of palmitate is associated with enhanced p300 binding and transcription factor recruitment to Il6 promoter regions. Gene silencing of p300 blocks this action of palmitate. RNA polymerase II recruitment was also enhanced at the Il6 promoter in palmitate/LPS-exposed cells. Acetylation levels of H3K9 and H3K18 were increased in monocytes treated with palmitate. Moreover, LPS stimulation of palmitate-treated cells led to increased levels of the transcriptionally permissive acetylation marks H3K9/H3K18 in the Il6 promoter compared with LPS alone. The effect of palmitate on LPS-induced IL-6 production was suppressed by the inhibition of histone acetyltransferases. Conversely, histone deacetylase inhibitors trichostatin A or sodium butyrate can substitute for palmitate in IL-6 production. Esterification of palmitate with CoA was involved, whereas ß-oxidation and ceramide biosynthesis were not required, for the induction of IL-6 and H3K9/H3K18 acetylation. Monocytes of obese individuals showed significantly higher H3K9/H3K18 acetylation and Il6 expression. Overall, our findings support a model in which increased levels of palmitate in obesity create a setting for LPS to potentiate IL-6 production via chromatin remodeling, enabling palmitate to contribute to metabolic inflammation.

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.

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.

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.

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.

Technical report: an online international weight control registry to inform precision approaches to healthy weight management.

BACKGROUND: Personalizing approaches to prevention and treatment of obesity will be a crucial aspect of precision health initiatives. However, in considering individual susceptibility to obesity, much remains to be learned about how to support healthy weight management in different population subgroups, environments and geographical locations. SUBJECTS/METHODS: The International Weight Control Registry (IWCR) has been launched to facilitate a deeper and broader understanding of the spectrum of factors contributing to success and challenges in weight loss and weight loss maintenance in individuals and across population groups. The IWCR registry aims to recruit, enroll and follow a diverse cohort of adults with varying rates of success in weight management. Data collection methods include questionnaires of demographic variables, weight history, and behavioral, cultural, economic, psychological, and environmental domains. A subset of participants will provide objective measures of physical activity, weight, and body composition along with detailed reports of dietary intake. Lastly, participants will be able to provide qualitative information in an unstructured format on additional topics they feel are relevant, and environmental data will be obtained from public sources based on participant zip code. CONCLUSIONS: The IWCR will be a resource for researchers to inform improvements in interventions for weight loss and weight loss maintenance in different countries, and to examine environmental and policy-level factors that affect weight management in different population groups. This large scale, multi-level approach aims to inform efforts to reduce the prevalence of obesity worldwide and its associated comorbidities and economic impacts. TRIAL REGISTRATION: NCT04907396 (clinicaltrials.gov) sponsor SB Roberts; Tufts University IRB #13075.

Titratable fixed-ratio combination of basal insulin plus a glucagon-like peptide-1 receptor agonist: A novel, simplified alternative to premix insulin for type 2 diabetes.

Despite novel therapeutic options, many people with type 2 diabetes (T2D) do not achieve their HbA1c targets. Given the progressive nature of T2D, many individuals not controlled with oral therapy will require advancement to injectable therapy using either a glucagon-like peptide-1 receptor agonist (GLP-1 RA), recently recommended as a first option, or traditionally a basal insulin. However, premix insulins remain frequently used, either as initial injectable therapy or as intensification from basal insulin. Premix insulin injections can potentially provide significant glycaemic improvements to basal insulin but at the expense of increased hypoglycaemia and weight gain and the need for multiple daily doses, which may affect treatment adherence. Real-world evidence suggests that glycaemic control often remains suboptimal with premix insulins. Fixed-ratio combinations (FRCs) of basal insulin and GLP-1 RAs provide a novel alternative to premix insulin for therapy intensification. While no direct comparisons between premix insulins and FRCs are available, results from meta-analyses suggest that FRCs may offer better HbA1c reductions, a lower risk of hypoglycaemia and less weight gain compared with premix insulin in a simplified treatment regimen. A head-to-head trial of T2D treatment intensification with premix insulin and a FRC of basal insulin plus a GLP-1 RA is currently in progress, which should help to clarify the outcomes for each treatment option. This review discusses the unmet needs of people with T2D treated with premix insulin and provides evidence supporting FRCs of basal insulin and GLP-1 RAs as an alternative treatment option.

Chia seed (Salvia hispanica L.) supplementation to the diet of adults with type 2 diabetes improved systolic blood pressure: A randomized controlled trial.

BACKGROUND: Functional food ingredients, such as dietary fiber, long-chain polyunsaturated fatty acids, and high-quality protein, have been shown to help control blood glucose concentration and lower high blood pressure (BP), as well as improving other cardiovascular disease risk factors. However, little research has assessed the impacts of consuming chia seeds, which are rich in these nutrients, on metabolic and physiological outcomes, and results are conflicting. AIM: The study aimed to investigate the possible effects of chia seeds on fasting blood glucose, insulin, glycated hemoglobin, BP, lipid profile, body weight, and the inflammatory marker - high-sensitivity C-reactive protein - in people with type 2 diabetes (T2DM). METHODS: Adults with T2DM (n = 42) were randomly assigned equally to the chia seed group, which consumed 40 g/day chia seeds for 12 weeks, or a control group, which did not consume any supplement. Blood samples were collected at baseline and after a 12-week intervention period to assess the study outcomes, such as glycemic control, BP, cardiovascular risk parameters including lipid profile, inflammatory marker, and body weight. RESULTS: Adjusted for gender and baseline values, the chia seed group had systolic BP (SBP) significantly reduced compared to control [t (1) = 2.867, p = 0.007, η 2 p = 0.174]. No differences were observed in any other parameter tested in the chia seed or control group. CONCLUSIONS: People with T2DM and hypertension, maintaining usual dietary consumption, physical activity pattern, and medications, had significantly reduced SBP compared to the control group when having consumed 40 g/d of chia seeds for 12 weeks.

Combination therapy with pioglitazone/exenatide improves beta-cell function and produces superior glycaemic control compared with basal/bolus insulin in poorly controlled type 2 diabetes: A 3-year follow-up of the Qatar study.

AIM: To examine the long-term efficacy of thiazolidinedione plus a glucagon-like peptide-1 receptor agonist versus basal-bolus insulin on glycaemic control and beta-cell function in patients with poorly controlled type 2 diabetes (T2D) on metformin plus sulphonylurea. MATERIALS AND METHODS: Three hundred and thirty-one patients with poorly controlled T2D were recruited over 3 years and were followed for an additional year. Subjects received a 75 g oral glucose tolerance test (OGTT) at baseline and at study end. After completing the baseline OGTT, subjects were randomized to receive either pioglitazone plus weekly exenatide (combination therapy) or basal/bolus insulin (insulin therapy) to maintain an HbA1c of less than 7.0%. The primary outcome of the study was the difference in HbA1c at study end between the two treatment groups. RESULTS: Both therapies caused a robust decrease in HbA1c. However, combination therapy caused a greater decrement (-1.1%, P < .0001) than insulin therapy, and more subjects in the combination therapy group (86%) achieved the American Diabetes Association goal of glycaemic control (HbA1c < 7.0%) than those in the insulin therapy group (44%) (P < .0001). Both therapies improved insulin secretion. However, the improvement in insulin secretion with combination therapy was 2.5-fold greater (P < .001) than with insulin therapy (50%). Insulin therapy caused more weight gain and hypoglycaemia. CONCLUSION: Both combination therapy and insulin therapy effectively reduced HbA1c in poorly controlled T2D on multiple oral agents. However, combination therapy produced a greater improvement in insulin secretion and decrease in HbA1c with a lower risk of hypoglycaemia.

TNF-α in Combination with Palmitate Enhances IL-8 Production via The MyD88- Independent TLR4 Signaling Pathway: Potential Relevance to Metabolic Inflammation.

Elevated levels of IL-8 (CXCL8) in obesity have been linked with insulin resistance and type 2 diabetes (T2D). The mechanisms that lead to the profound production of IL-8 in obesity remains to be understood. TNF-α and saturated free fatty acids (FFAs) are increased in obese humans and correlate with insulin resistance. Hence, we sought to investigate whether the cooccurrence of TNF-α and FFAs led to increase the production of IL-8 by human monocytes. We found that co-stimulation of human monocytes with palmitate and TNF-α led to increased IL-8 production as compared to those stimulated with palmitate or TNF-α alone. The synergistic production of IL-8 by TNF-α/palmitate was suppressed by neutralizing anti- Toll like receptor 4 (TLR4) antibody and by genetic silencing of TLR4. Both MyD88-deficient and MyD88-competent cells responded comparably to TNF-α/Palmitate. However, TIR-domain-containing adapter-inducing interferon (TRIF) inhibition or interferon regulatory transcription factor 3 (IRF3) knockdown partly blocked the synergistic production of IL-8. Our human data show that increased adipose tissue TNF-α expression correlated positively with IL-8 expression (r = 0.49, P = 0.001). IL-8 and TNF-α correlated positively with macrophage markers including CD68, CD163 and CD86 in adipose tissue. These findings suggest that the signaling cross-talk between saturated fatty acid palmitate and TNF-α may be a key driver in obesity-associated chronic inflammation via an excessive production of IL-8.

Diabetes and TelecommunicationS (DATES) study to support self-management for people with type 2 diabetes: a randomized controlled trial.

BACKGROUND: The increasing prevalence of type 2 diabetes and suboptimal glycaemic control in Kuwait requires novel, wide-reaching, low-cost interventions to motivate and mobilise individuals towards more effective self-management. More than 2 million people in Kuwait own mobile phones. We will test whether automated personalised health text messages based on principles of motivational interviewing and are responsive to biodata delivered remotely is potentially effective in improving glycaemic control compared to usual care. METHODS: This is a two-arm parallel single-blind randomised controlled trial of 572 individuals with type 2 diabetes in Kuwait. We will develop a culturally appropriate database of text messages supporting positive lifestyle changes in type 2 diabetes. A computer programme will deliver over 400 text messages over a 12-month period using algorithms which provide participants with information on diet and physical activity as well as personalised messages regarding motivators to change behaviours. Individuals aged 18-75 years with established type 2 diabetes who are fluent in Arabic or English and officially resident in Kuwait will be identified via screening of hospital diabetes clinic and primary care practices and invited to participate. A sample of 572 participants will be randomised to usual care or usual care plus the DATES text message intervention. Randomisation will be conducted by an independent Clinical Trials Unit and researchers collecting baseline and outcome data will be blinded to treatment allocation. The primary outcome is change in HbA1c and weight at 12 months in both study arms. Secondary outcomes will include changes in physical activity, fasting lipids and quality of life in both study arms. DISCUSSION: The potential of mobile phones in improving diabetes self-care in settings with a high prevalence of diabetes and widespread mobile phone usage has face validity. Mobile phones and text messaging are an understudied virtual communication media which can deliver discrete focused psychological support to motivate and enable diabetes self-care changes. TRIAL REGISTRATION: ISRCTN10342151 . 11/03/2015.

Effect of Black Tea Consumption on Intracellular Cytokines, Regulatory T Cells and Metabolic Biomarkers in Type 2 Diabetes Patients.

The present study was undertaken to evaluate the effects of black tea intake on inflammatory cytokines and metabolic biomarkers in Type 2 diabetes mellitus (T2DM). Thirty patients with T2DM were randomly assigned either to a High Intake (HI) group, consuming three cups (600 mL) of black tea per day; and a Low Intake (LI) group, administered 1 cup (200 mL) per day, each during a 12-week period. Intracellular cytokine expression, regulatory T cells (Treg), glycemic and lipid profiles were measured at baseline and following the tea intake period. Tea consumption correlated with major effects measured in peripheral blood of subjects that included significantly reduced glycated hemoglobin (HbA1c) levels, along with increased regulatory T cells CD3+ CD4+ CD25+ FOXP3, CD3+ CD4+ IL-10+ cells (an immunosuppressive phenotype), reduced (pro-inflammatory) CD3+ CD4+ IL-17+ cells and reduced Th1-associated CD3+ CD4+ IFN-Υ+ cells. Tea consumption was also observed to abolish the significance of an inverse correlation between total serum cholesterol and representation of CD4+ IL-4+ T cells, which may reflect protection against atopy-related oxidative stress. Outcomes of this study describe both advantages and limitations to consumption of black tea as an aid to sustained health maintenance by persons at-risk for TD2M and related obesity-associated metabolic syndromes.

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.

Reformulating ice cream to improve postprandial glucose response: an opportunity for industry to create shared value.

Ultra-processed foods are associated with metabolic dysfunction and driving chronic diseases. The Metabolic Matrix is a tool used to reformulate products to promote positive metabolic outcomes. The Kuwait Danish Dairy Company (KDD) has used this tool to develop a no-added-sugar products. This clinical trial tested the glycaemic response of a no-added-sugar ice cream in individuals with type 2 diabetes. The hypothesis was that the no-added-sugar ice cream would have a substantially better postprandial glycemic response than conventional ice cream in patients with type 2 diabetes. In this randomized cross over designed study, postprandial glycemic response was measured after 300 grams of no-added-sugar ice cream or normal ice cream was consumed. Despite similar composition and palatability, the postprandial responses were better with the no-added sugar ice cream, albeit that the natural sugar in the product still resulted in a marked postprandial glycaemic response. This finding emphasizes the necessity of clearly communicating to both patients and healthcare professionals that "no-added-sugar" does not equate to "zero total sugar." The path to improved metabolic health involves not only product improvement but also transparent messaging to enable informed dietary choices. Reformulation resulting in palatable no-added sugar products provides an opportunity for companies to Create Shared Value by addressing the important social problems such as obesity and type 2 diabetes, by creating scalable solutions, that are profitable. Clinical trial registration:ClinicalTrials.gov, identifiers NCT06135935.

Association of Physical Activity and Sleep Metrics with Depression in People with Type 1 Diabetes.

Objective: This study aimed to investigate the association of physical activity and sleep metrics, measured via wrist-worn accelerometers, with depression in people with type 1 diabetes. Patients and Methods: People with type 1 diabetes were recruited from the Dasman Diabetes Institute in Kuwait and were invited to wear a wrist-worn accelerometer device for 7 days. Mean physical activity (overall acceleration), inactivity, light activity, moderate activity, vigorous activity, the distribution of physical activity intensity (intensity gradient), sleep duration and sleep efficiency were quantified from the accelerometer data. The associations of these metrics with depression were investigated using multiple linear regression. Results: A total of 551 people with type 1 diabetes (age 33.1 (9.5) years) were included. Overall physical activity (B = -0.09, CI = -0.14 to -0.04), moderate intensity activity (B = -0.02, CI = -0.02 to -0.01), vigorous intensity activity (B = -0.16, CI = -0.27 to -0.05), and the intensity gradient (B = -2.11, CI = -3.51 to -0.72) were negatively associated with depression score (p < 0.01) and these associations remain significant even after adjustment for age, sex, diabetes duration, and BMI. However, sleep duration and efficiency were not associated with depression. After mutual adjustment overall physical activity (B = -0.07, CI = -0.12 to -0.01), but not the intensity gradient (B = -0.90, CI = -2.47 to 0.68), remained associated with depression. Conclusion: Overall, moderate and vigorous physical activity, and the intensity gradient were associated with lower symptoms of depression. Overall physical activity, rather than the distribution of activity intensity, appears more important in depression. This information can help guide physical activity interventions to improve depression in people with type 1 diabetes.

Seasonal differences in physical activity, sedentary behaviour, and sleep patterns in people with type 1 diabetes in Kuwait.

AIMS: The main aim of the current study was to measure physical activity, sedentary behaviors and sleep levels across the different seasons in people with type 1 diabetes in Kuwait. METHODS: A prospective cross-sectional study was conducted from August 2021 to September 2022. Physical activity and sleep metrics were measured over a 7-day period with a wrist-worn accelerometer (GENEActiv). Overall physical activity was measured as a Euclidean Norm Minus One in milli gravitational units (mg). Accelerometer metrics were compared across the seasons and between the sex. RESULTS: A total of 784 people with type 1 diabetes participated. Mean daily physical activity was 25.2 mg (SD = 7.3). Seasonal differences were seen in overall physical activity (p = 0.05), inactivity (p = 0.04), light activity (p = 0.001), the intensity gradient (p = 0.001) and sleep efficiency (p = 0.02). Poorer metrics were generally seen in Spring and Summer. Overall physical activity, moderate and vigorous physical activity, and inactivity were significantly higher in males compared to females (p ≤ 0.02). Females had a longer sleeping duration (p = 0.02), and higher sleep efficiency (p = 0.04) and light physical activity (p = 0.01). Overall physical activity and the intensity gradient were negatively associated with HbA1c (both p = 0.01). CONCLUSIONS: Physical activity levels were generally low and sleep poor in people with type 1 diabetes in Kuwait and these varied by sex and season. The current data are useful to target and develop interventions to improve physical activity and glycemic control.

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.

Sour cherry seed kernel extract increases heme oxygenase-1 expression and decreases representation of CD3+ TNF-α+ and CD3+IL-8+ subpopulations in peripheral blood leukocyte cultures from type 2 diabetes patients.

The present study evaluates a hypothesis that sour cherry (Prunus cerasus) seed extracts (SCE) modulate CD3+ T lymphocyte activity in ways predictive of potential for uses of SCE in management of inflammatory diseases. Peripheral blood mononuclear cells (PBMC) from 12 type 2 diabetes (T2DM) patients and eight healthy control subjects were cultured 24 h with 100 ng/ml lipopolysaccharide (LPS) to increase inflammatory signaling and co-incubated with 0.5-100 µg/ml SCE. Cultures were evaluated by two-color flow cytometry for percent representation of CD3+ IL8+ and CD3+TNF-α cells which express interleukin-8 (IL-8), and tumor necrosis factor-α, (TNF-α+) respectively, and by enzyme-linked immunoassay for lymphocyte-associated heme oxygenase-1 (HO-1, known to be induced by SCE). SCE dosage ranges of 0.5-100 µg/ml in cell cultures significantly suppressed LPS-increased CD3+TNF-α+ and CD3+IL8+ representation from all participants (p < 0.05), with greater pharmacological effect noted in suppression of CD3+TNF-α+ noted in cells from T2DM patients versus healthy control subjects. These effects correlated with increased HO-1 expression in SCE-treated PBMC from all subjects (p < 0.05). Since TNF-α and IL-8 are diagnostic/prognostic biomarkers for many inflammatory syndromes, the capacity of SCE to down-regulate representation of cells that express them suggests potential for therapeutic use of SCE in T2DM and other diseases.