Clusters of adipose tissue dysfunction in adults with type 2 diabetes identify those with worse lipidomic profile despite similar glycaemic control.

AIMS: To investigate clusters of adipose tissue dysfunction, that is, with adipose tissue insulin resistance (ADIPO-IR) and large waist circumference (WC), identify a worse lipidomic profile characterised by a high proportion of lipids rich in saturated fatty acids (SFA). MATERIALS AND METHODS: Hierarchical clustering based on WC and ADIPO-IR (calculated as fasting plasma non-esterified fatty acids times fasting plasma insulin, FFA×INS), was performed in 192 adults with overweight/obesity and type 2 diabetes (T2D) treated with metformin (HbA1c = 7.8%). Free fatty acid composition and lipidomic profile were measured by mass spectrometry (GC-MS and LC-MSQTOF). Indexes of fatty acid desaturation (stearoyl-coA desaturase-1 activity, SCD116 = palmitoleic acid/palmitic acid and SCD118 = oleic acid/stearic acid) and of insulin resistance (HOMA-IR) were also calculated. RESULTS: Three clusters were identified: CL1 (ADIPO-IR = 4.9 ± 2.4 and WC = 96±7 cm, mean ± SD), CL2 (ADIPO-IR = 6.5 ± 2.5 and WC = 114 ± 7 cm), and CL3 (ADIPO-IR = 15.0 ± 4.7 and WC = 107 ± 8 cm). Insulin concentrations, ADIPO-IR, and HOMA-IR significantly increased from CL1 to CL3 (all p < 0.001), while fasting glucose concentrations, HbA1c, dietary lipids and caloric intake were similar. Moreover, CL3 showed significantly higher concentrations of monounsaturated free fatty acids, oleic and palmitoleic acids, triglycerides (TAG) rich in saturated FA and associated with de novo lipogenesis (i.e., TAG 46-50), higher SCD116, SCD118, ceramide (d18:0/18:0), and phosphatidylcholine aa(36:5) compared with CL1/CL2 (all p < 0.005). CONCLUSIONS: High ADIPO-IR and large WC identify a worse lipid profile in T2D characterised by complex lipids rich in SFA, likely due to de novo synthesis given higher plasma monounsaturated FFA and increased desaturase activity indexes. REGISTRATION NUMBER TRIAL: ID NCT00700856 https://clinicaltrials.gov.

Compositional profiling and bioefficacy studies of pulses-supplemented isocaloric designer biscuits for recently diagnosed diabetic individuals.

This study addresses global concerns about diabetes mellitus by exploring a novel approach to manage hyperglycemia through pulses-supplemented designer biscuits. Control and designer biscuits were prepared with varying proportions of wheat flour and pulses (chickpea, mungbean). The pulses-supplemented biscuits exhibited increased protein content and reduced readily available carbohydrates. Selected designer biscuits, with 12.5 % incorporation of chickpea and mungbean pulse flour, demonstrated significantly lower glycemic index (69.17 ± 5.01) and higher satiety index (122.19 ± 8.85) compared to control biscuits. These showed 13 % less glycemic index and 9 % higher satiety index as compared to control biscuits. A four-week bio-efficacy trial involving diabetic subjects consuming these biscuits as a routine snack resulted in an 11.45 % decrease in fasting blood glucose and a 19.15 % reduction in random blood glucose levels. Insulin and HDL levels also significantly improved. The study concludes that these designer biscuits possess a hypoglycemic effect, offering a potential dietary intervention for managing diabetes.

Current barriers to initiating insulin therapy in individuals with type 2 diabetes.

Insulin is an essential drug in the treatment of diabetes, often necessary for managing hyperglycemia in type 2 diabetes mellitus (T2DM). It should be considered in cases of severe hyperglycemia requiring hospitalization, after the failure of other treatments, in advanced chronic kidney disease, liver cirrhosis, post-transplant diabetes, or during pregnancy. Moreover, in specific patient subgroups, early initiation of insulin is crucial for hyperglycemia control and prevention of chronic complications. Clinical guidelines recommend initiating insulin when other treatments fail, although there are barriers that may delay its initiation. The timing of initiation depends on individual patient characteristics. Typically, insulinization starts by adding basal insulin to the patient's existing treatment and, if necessary, progresses by gradually introducing prandial insulin. Several barriers have been identified that hinder the initiation of insulin, including fear of hypoglycemia, lack of adherence, the need for glucose monitoring, the injection method of insulin administration, social rejection associated with the stigma of injections, weight gain, a sense of therapeutic failure at initiation, lack of experience among some healthcare professionals, and the delayed and reactive positioning of insulin in recent clinical guidelines. These barriers contribute, among other factors, to therapeutic inertia in initiating and intensifying insulin treatment and to patients' non-adherence. In this context, the development of once-weekly insulin formulations could improve initial acceptance, adherence, treatment satisfaction, and consequently, the quality of life for patients. Currently, two once-weekly basal insulins, insulin icodec and basal insulin BIF, which are in different stages of clinical development, may help. Their longer half-life translates to lower variability and reduced risk of hypoglycemia. This review addresses the need for insulin in T2DM, its positioning in clinical guidelines under specific circumstances, the current barriers to initiating and intensifying insulin treatment, and the potential role of once-weekly insulin formulations as a potential solution to facilitate timely initiation of insulinization, which would reduce therapeutic inertia and achieve better early control in people with T2DM.

Protein hydrolysates of Moringa oleifera seed: Antioxidant and antihyperglycaemic potential as ingredient for the management of type-2 diabetes.

New plant proteins with high nutritional quality and biological properties are actively searched worldwide. Moringa oleifera seed protein isolate was prepared from defatted flour and hydrolyzed using four proteases namely trypsin, pepsin, Alcalase, and thermolysin. Then, antioxidant activity and cellular glucose uptake properties of the hydrolysates were assessed. A high degree of hydrolysis was obtained for hydrolysate prepared using trypsin (60.07%), followed by pepsin (57.14%), Alcalase (50.68%), and thermolysin (45.45%). Thermolysin hydrolysate was the most antioxidant efficient (IC50 0.15 and 0.74 mg/mL for 2,2'-azino-bis(acide 3-ethylbenzothiazoline-6-sulfonique) diammonium salt (ABTS) and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, respectively). Trypsin hydrolysate stimulated high glucose uptake by yeast cells (12.34-35.28%). In the absence of insulin, Alcalase hydrolysate was the most efficient for glucose uptake by the muscle, with the rate ranging from 22.03% to 29.93% after 30 min, then from 29.55% to 34.6% after 60 min. The four hydrolysates improved glucose uptake by the muscle in the presence of insulin with the rate ranging from 46.88% to 58.03% after 30 min, and from 50% to 58.18% after 60 min. Therefore, Moringa oleifera seed proteins could be used to prepare peptides as components of functional foods for the management of type-2 diabetes.

Circulating afamin positively correlated with the miR-122 expression and type 2 diabetes mellitus-related phenotype according to the duration of diabetes.

Background: Afamin is a hepatokine that involves in glucose and lipids metabolism. miR-122 is mainly expressed in liver and involves in lipid and carbohydrate metabolism. This study aimed at investigating the circulating afamin, its correlation with type 2 diabetes mellitus (T2DM) and miR-122 gene expression in T2DM patients and healthy control subjects according to the duration of diabetes. Methods: This case-control study included 220 participants, with 100 individuals serving as controls and 120 individuals diagnosed with type 2 diabetes mellitus (T2DM). The miR-122 gene expression was assessed using real-time PCR. The serum concentration of biochemical parameters such as glucose levels, lipid profile, and small-dense low-density lipoprotein (sdLDL) were measured using colorimetric kits. Circulating afamin and insulin levels were assayed using an ELISA kit. Glycated hemoglobin (HbA1c) was measured using capillary electrophoresis. Results: Circulating afamin level was significantly higher in T2DM patients compared to the control group, (73.8 ± 10.8 vs. 65.9 ± 8.7, respectively; P < 0.001). Similarly, miR122 expression was significantly increased in T2DM patients compared to healthy control subjects (4.24 ± 2.01 vs. 1.00 ± 0.85, respectively; P < 0.001). Among patients diagnosed with T2DM, those with longstanding diabetes (>5 years) exhibited significantly higher levels of circulating afamin and miR-122 expression compared to individuals with a shorter duration of diabetes (≤5 years) (P < 0.05). Circulating afamin levels were significantly correlated with waist circumference, small-dense low-density lipoprotein (sdLDL), fasting blood sugar (FBS), insulin, resistance to insulin, and miR-122 expression, depending on the duration of the disease (P < 0.05). Furthermore, the performance of afamin as a diagnostic marker for T2DM was confirmed through receiver operating characteristic (ROC) analysis, yielding an area under the curve (AUC) of 0.7 (P < 0.001). Conclusions: Circulating afamin involved in the T2DM-related complications and its concentration is positively correlated to the miR-122 expression, especially in patient with longstanding diabetes.

Audit of essential medicine listing and registration status of medicines on standard treatment guidelines in Kenya, Tanzania and Uganda: Case study of malaria, tuberculosis, hypertension and type 2 diabetes mellitus.

Objectives: To determine alignment between national and World Health Organization (WHO) treatment recommendations, medicines prioritisation in country's essential medicines list (EML), and medicines availability in National drug register. Design: An audit of medicines for malaria, tuberculosis, hypertension and type 2 diabetes mellitus listed in the national standard treatment guidelines (STGs) of Kenya, Tanzania and Uganda, as of March 2021, against WHO treatment guidelines, and respective country EML and National drug register. Setting: Not applicable. Participants: None. Main outcome measures: Proportion of medicine in country's STGs that align with WHO treatment recommendations, country's EML and country's drug register. Results: Some disease areas had two sets of treatment guidelines - national STGs and disease-specific treatment guidelines (DSGs) developed at different times with different recommended medicines. Both STGs and DSGs included medicines not recommended by the WHO or not listed on the country EML and drug register. Non-WHO-recommended medicines accounted for 17/68 (25%), 10/57 (18%) and 3/30 (10%) of all STG medicines in Kenya, Tanzania and Uganda, respectively. For tuberculosis, the numbers and proportion of STG medicines listed on the respective national EMLs were 2/6 (33%), 15/19 (79%) and 4/5 (80%) in Kenya, Tanzania and Uganda. All tuberculosis medicines included in Kenya's and Uganda's STGs were registered compared with only 12/19 (63%) tuberculosis medicines in Tanzania's STG. Conclusions: Alignment between treatment guidelines, EMLs and drug registers is crucial for effective national pharmaceutical policy. Research is needed to understand the inclusion of medicines on STGs and DSGs which fall outside WHO treatment guidelines; the non-alignment of some STGs and DSGs, and STGs and DSGs including medicines which are not on country EML and drug register.

Correlation Between Thyroid-Related Hormones and Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients with Normal Thyroid Function: A Retrospective Study.

Purpose: To investigate the correlation between thyroid-related hormones and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM). Patients and Methods: Patients with T2DM admitted to our hospital between January 2023 and June 2023 were retrospectively analyzed. The patients were divided into DR and non-diabetic retinopathy (NDR) groups according to whether DR occurred. Thyroid function-related hormones (TSH, FT3, and FT4), blood glucose indices (FBG and HbA1c), and blood lipid indices (HDL-C, LDL-C, TC, and TG) of the two groups were analyzed by univariate and multivariate logistic regression to explore the risk factors for DR. Pearson correlation analysis and multiple stepwise regression analysis were used to investigate the correlation of TSH or FT3 with FBG, HbA1c, and TG in DR patients. Results: Of the 286 patients with T2DM included in this study, 101 (35.31%) developed DR and 185 (64.69%) did not. High TG, FBG, HbA1c, and TSH and low FT3 levels were independent risk factors for DR in T2DM patients. TSH positively correlated with TG, whereas FT3 negatively correlated with TG and HbA1c in T2DM patients with DR. Conclusion: Higher TSH and lower FT3 in T2DM patients with normal thyroid function may affect glucose and lipid metabolism, thereby increasing the risk of DR.

Study on the Interaction Between C3 Gene Polymorphism and Environment in Patients with Type 2 Diabetes Combined with Coronary Artery Disease.

Objective: This study was conducted to investigate the combined effect of genetic variation in the C3 gene and environmental factors on the risk of type 2 diabetes mellitus(T2DM) and coronary artery disease(CAD) in a population from Xinjiang, China. Methods: We conducted a hospital-based case-control study with 896 participants (217 with T2DM+CAD and 679 healthy controls). A polymerase chain reaction-ligase detection reaction was used to identify and genotype TagSNPs in the C3 gene, and the influence of the interaction of two SNP loci (rs1047286 and rs11569562) with the environment on T2DM combined with CAD was evaluated through clinical data, statistical analysis of gene frequencies, and the formation of a gene-environment interaction model. Results: We find that rs11569562 GG is an independent protective factor for T2DM and CAD (OR=0.353, p=0.012), and the variants at its locus may be closely associated with Activated Partial Thromboplastin Time (APTT), lipoprotein a (Lp(a)), Apolipoprotein A (APOA), Aspartate Aminotransferase (AST), Aspartate Aminotransferase (ALT) and AST/ALT levels (all P < 0.05); its GG genotype has significantly lower Gensini score and number of stenoses than the GA and AA genotypes. Multifactorial dimensionality reduction (MDR) finds a strong correlation between rs11569562 and AST (antagonistic effect) (4.44%); the role of rs11569562's influence remains strong in terms of the independent effects of each attribute (1.72%). Conclusions: In this study, we find that variants in the C3 gene loci rs11569562 are associated with the incidence of type 2 diabetes mellitus combined with coronary heart disease in a Chinese population. It is expected to be an independent predictor of type 2 diabetes mellitus combined with coronary heart disease in the Chinese population. Rs11569562 may be associated with lipid levels and coagulation molecules. Clinical Trial Registration: This trial registered on in 2014 at the China Clinical Trials Registry (ChiCTR-TRC-14005114).

Type 2 Diabetes, the Epidemic: Trends in Prevalence and Incidence, 2004-2020.

Aims/Hypothesis: Only a few studies reported the incidence of type 2 diabetes (T2D). Understanding recent trends in diabetes is vital for planning future diabetes care. This study updated national trends in the prevalence and incidence of type 2 diabetes (T2D) in the Netherlands from 2004-2020. Methods: The DIAbetes, MANagement and Treatment (DIAMANT) cohort was used. A cross-sectional design with yearly measurements for the study period was used. The prevalence was calculated by dividing the total number of people with T2D by the total number of all residents. The incidence was calculated by dividing new cases of T2D by the resident population at risk during the calendar year of interest. Results: Among men, the prevalence of T2D in the Netherlands increased from 2.3% in 2004 to 6.3% in 2020. Women's prevalence increased from 2.3% in 2004 to 5.3% in 2020. During 2005-2009, the incidence rate for both men and women was relatively stable Between 2010 and 2020, the incidence rate fell about 1.5 per 1000 in both men and women. Conclusion: From 2004-2020, the prevalence of T2D in the Netherlands more than doubled, with a decreasing incidence from 2010 onwards.

Research in context What is already known about this subject? Many studies have reported the increasing prevalence of type 2 diabetes (T2D). However, only a few studies reported the incidence.In a recent systematic review of all these studies, the incidence fell in over a third of the most high-income populations and increased in a minority of populations. Data from the Netherlands were included, but they date back to 1996.Understanding recent trends in diabetes, the prevalence and incidence are vital for planning future diabetes care.What is the key question? To update national trends in the prevalence and incidence of T2D in the Netherlands for 2004-2020.What are the new findings? During 2004-2020, the prevalence of T2D in the Netherlands more than doubled, with a decreasing incidence from 2010 onwards.How might this impact on clinical practice in the foreseeable future? It demonstrates the effectiveness of preventive strategies, public health education and awareness campaigns contributing to this trend.

Targeting metabolic-associated fatty liver disease in diabetic kidney disease: A call to action.

Nonalcoholic fatty liver disease or metabolic-associated fatty liver disease (MAFLD) is a common condicion with increasing prevalence and incidence, specially in patients with type 2 diabetes mellitus (T2DM). Both cardiovascular and renal disease are clearly increased in these patients, particularly in those with diabetic nephropathy. In the liver-heart-kidney-metabolic axis, the common pathophysiological basis of MAFLD, cardiovascular disease (CVD), chronic kidney disease (CKD), and T2DM is the same. The clinical relationship between all of them is clear and is multidirectional: MAFLD may precede the development of cardiovascular and renal disease, and may also worsen the prognosis of these complications once developed. In this review we emphasize the importance of targeting MAFLD in Diabetic kidney disease, with the goal of detecting high-risk patients in order to improve their prognosis.

Enhancing type 2 diabetes treatment through digital plans of care - a randomized controlled trial: evaluation of change in patient reported outcome measures.

BACKGROUND: We investigated how a personalized care-planning software and linked mobile-app may aid people to self-manage their type 2 diabetes (T2D) more effectively. RESEARCH DESIGN AND METHODS: People with T2D and glycated hemoglobin (HbA1c) greater than 58 mmol/mol (7.5%) were randomized to either an intervention group receiving a personalized care plan, or the control group receiving usual care. Quality of life (QoL) was measured for both groups using validated questionnaires and one-on-one interviews with a subset of 12 participants from each group. RESULTS: QoL for the active treatment group increased, by their EQ -5D-5 L score increasing on average by 0.046, whereas it decreased for the control group on average by 0.009. The EQ Visual Analogue Score (VAS) of the intervention group also increased by 8.2%, whereas the control group had a reduction in EQ VAS score of 2.8% (p = 0.008 for difference). CONCLUSION: In this prospective RCT, the findings point to how the provision of personalized care plans can result in an improvement in individuals' self-rated QoL. This may lead to longer term health benefits.

Metformin: Past, Present, and Future.

PURPOSE OF REVIEW: This review provides the most recent update of metformin, a biguanide oral antihyperglycemic drug used as a first-line treatment in type 2 diabetes mellitus. RECENT FINDINGS: Metformin continues to dominate in the world of antidiabetics, and its use will continue to rise because of its high efficiency and easy availability. Apart from type 2 diabetes, research is exploring its potential in other conditions such as cancer, memory loss, bone disorders, immunological diseases, and aging. Metformin is the most prescribed oral antidiabetic worldwide. It has been in practical use for the last six decades and continues to be the preferred drug for newly diagnosed type 2 diabetes mellitus. It reduces glucose levels by decreasing hepatic glucose production, reducing intestinal glucose absorption, and increasing insulin sensitivity. It can be used as monotherapy or combined with other antidiabetics like sulfonylureas, DPP-4 inhibitors, SGLT-2 inhibitors, or insulin, improving its efficacy. Metformin can be used once or twice daily, depending on requirements. Prolonged usage of metformin may lead to abdominal discomfort, deficiency of Vitamin B12, or lactic acidosis. It should be used carefully in patients with renal impairment. Recent studies have explored additional benefits of metformin in polycystic ovarian disease, gestational diabetes mellitus, cognitive disorders, and immunological diseases. However, more extensive studies are needed to confirm these additional benefits.

Perceptions and Experiences of People with Obesity and Type 2 Diabetes Around Appetite and Eating Behaviors: A Qualitative Study.

INTRODUCTION: Chronic weight management and treatments for type 2 diabetes (T2D) involve a combination of lifestyle-based (diet, exercise) and pharmaceutical interventions. In people with obesity or T2D, understanding the impact of drivers/triggers on appetite and eating behaviors can be crucial to successful medical management. This study aimed to characterize perceptions and experiences regarding appetite and eating behaviors among people with obesity or T2D and identify drivers/triggers of food choices. METHODS: This non-interventional, cross-sectional, qualitative study utilized semi-structured concept elicitation interviews to explore the perceptions of people with obesity and/or T2D around appetite, eating behaviors and drivers/triggers of food choices. Adult US residents (≥ 18 years) with stable body weight (± 5 kg) in the 3 months preceding participation were included in the study. RESULTS: Forty-five participants (obesity: n = 15; overweight: n = 10; T2D: n = 20) were interviewed. Interviews were audio-recorded and transcribed verbatim for analysis. A subset of participants described eating behaviors on smartphone-based app tasks over 5 days. Most (> 96%) discussed the influence of hunger, cravings and satiety on food choices. Participants identified 22 drivers/triggers (including health, 95.6%; culture/heritage, 93.3%; location, 91.1%; stress, 88.8%). Participants also discussed associations between drivers/triggers and eating behavior concepts (appetite, hunger, cravings, satiety, motivation/determination). A conceptual model illustrating eating behavior concepts and related drivers/triggers was developed. The concept elicitation interviews identified a multitude of drivers and triggers and characterized the association of such drivers/triggers with seven core patient-reported concepts encompassing eating behaviors. CONCLUSION: The findings build upon existing models of factors influencing food choices. Findings confirm prior research regarding impact of drivers/triggers on food choice in people with obesity and T2D and indicate underlying disease state does not appear to influence eating behaviors in people with stable body weight.

Diagnosis and Risk Factors of Prediabetes and Diabetes in People Living with HIV- Evaluation of Clinical and Microbiome Parameters.

Diabetes is more common among people living with HIV (PLWH), as compared with healthy individuals. In a prospective multicenter study (N = 248), we identified normoglycemic (48.7%), prediabetic (44.4%) and diabetic (6.9%) PLWH. HbA1c and fasting blood glucose (FBG) sensitivity in defining dysglycemia was 96.8%, while addition of oral glucose tolerance test led to reclassification of only 4 patients. Inclusion of 93 additional PLWH with known DM enabled identification of multiple independent predictors of dysglycemia or diabetes: older age, higher BMI, Ethiopian origin, HIV duration, lower integrase inhibitor exposure and advanced disease at diagnosis. Shotgun metagenomic microbiome analysis revealed 4 species that were significantly expanded with hyperglycemia/hyperinsulinemia, and 2 species that were differentially more prevalent in prediabetic/diabetic PLWH. Collectively, we uncover multiple potential host and microbiome predictors of altered glycemic status in PLWH, while demonstrating that FBG and HbA1C likely suffice for diabetes screening. These potential diabetic predictors merit future prospective validation.

Patterns of initial and first-intensifying antidiabetic drug utilization among patients with type 2 diabetes mellitus in Scotland, 2010-2020: A retrospective population-based cohort study.

AIM: To evaluate the utilization and prescribing patterns of antidiabetic drugs (ADDs) for patients with type 2 diabetes mellitus (T2DM) at treatment initiation and first intensification. METHODS: A retrospective cohort study was performed using linked routinely collected data of patients with T2DM who received ADDs between January 2010 and December 2020 in Scotland. The prescribing patterns were quantified using frequency/percentages, absolute/relative change, and trend tests. RESULTS: Overall, 145 909 new ADD users were identified, with approximately 91% (N = 132 382) of patients receiving a single ADD at first treatment initiation. Metformin was the most often prescribed monotherapy (N = 118 737, 89.69%). A total of 50 731 patients (39.40%) who were started on metformin (N = 46 730/118 737, 39.36%) or sulphonylurea (SU; N = 4001/10 029, 39.89%) monotherapy had their treatment intensified with one or more additional ADD. Most initial-metformin (45 963/46 730; 98.36%) and initial-SU users (3894/4001; 97.33%) who added further drugs were intensified with single ADDs. SUs (22 197/45 963; 48.29%) were the most common first-intensifying monotherapy after initial metformin use, but these were replaced by sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2019 (SGLT2 inhibitors: 2039/6065, 33.62% vs. SUs: 1924/6065, 31.72%). Metformin was the most frequently added monotherapy to initial SU use (2924/3894, 75.09%). Although the majority of patients received a single ADD, the use of combination therapy significantly increased over time. Nevertheless, there was a significant increasing trend towards prescribing the newer ADD classes (SGLT2 inhibitors, dipeptidyl peptidase-4 inhibitors) as monotherapy or in combination compared with the older ones (SUs, insulin, thiazolidinediones) at both drug initiation and first intensification. CONCLUSIONS: An overall increasing trend in prescribing the newer ADD classes compared to older ADDs was observed. However, metformin remained the most commonly prescribed first-line ADD, while SGLT2 inhibitors replaced SUs as the most common add-on therapy to initial metformin use in 2019.

Cardiovascular health metrics defined by Life's Essential 8 scores and subsequent macrovascular and microvascular complications in individuals with type 2 diabetes: A prospective cohort study.

AIM: To investigate the association between cardiovascular health metrics defined by Life's Essential 8 (LE8) scores and vascular complications among individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: This prospective study included 11 033 participants with T2D, all devoid of macrovascular diseases (including cardiovascular and peripheral artery disease) and microvascular complications (e.g. diabetic retinopathy, neuropathy and nephropathy) at baseline from the UK Biobank. The LE8 score comprised eight metrics: smoking, body mass index, physical activity, non-high-density lipoprotein cholesterol, blood pressure, glycated haemoglobin, diet and sleep duration. Cox proportional hazards models were established to assess the associations of LE8 scores with incident macrovascular and microvascular complications. RESULTS: During a median follow-up of 12.1 years, we identified 1975 cases of incident macrovascular diseases and 1797 cases of incident microvascular complications. After adjusting for potential confounders, each 10-point increase in the LE8 score was associated with an 18% lower risk of macrovascular diseases and a 15% lower risk of microvascular complications. Comparing individuals in the highest and lowest quartiles of LE8 scores revealed hazard ratios of 0.55 (95% confidence interval 0.47-0.62) for incident macrovascular diseases, and 0.61 (95% confidence interval 0.53-0.70) for incident microvascular complications. This association remained robust across a series of sensitivity analyses and nearly all subgroups. CONCLUSION: Higher LE8 scores were associated with a lower risk of incident macrovascular and microvascular complications among individuals with T2D. These findings underscore the significance of adopting fundamental strategies to maintain optimal cardiovascular health and curtail the risk of developing diabetic vascular complications.

Immunogenicity, efficacy, and safety of biosimilar insulin glargine (Gan & Lee glargine) compared with originator insulin glargine (Lantus®) in patients with type 2 diabetes after 26 weeks' treatment: A randomized open label study.

AIM: To evaluate the equivalence of immunogenicity, safety and efficacy of Gan & Lee (GL) Glargine (Basalin®; Gan & Lee Pharmaceutical) with that of the reference product (Lantus®) in adult participants with type 2 diabetes mellitus. METHODS: This was a phase 3, multicenter, open-label, equivalence trial conducted across 57 sites. In total, 567 participants with type 2 diabetes mellitus were randomized in a 1:1 ratio to undergo treatment with either GL Glargine or Lantus® for 26 weeks. The primary endpoint was the proportion of participants in each treatment arm who manifested treatment-induced anti-insulin antibodies (AIA). Secondary endpoints included efficacy and safety metrics, changes in glycated haemoglobin levels, and a comparative assessment of adverse events. Results were analysed using an equivalence test comparing the limits of the 90% confidence interval (CI) for treatment-induced AIA development to the prespecified margins. RESULTS: The percentages of participants positive for treatment-induced glycated haemoglobin by week 26 were similar between the GL Glargine (19.2%) and Lantus® (21.3%) treatment groups, with a treatment difference of -2.1 percentage points and a 90% CI (-7.6%, 3.5%) (predefined similarity margins: -10.7%, 10.7%). The difference in glycated haemoglobin was -0.08% (90% CI, -0.23, 0.06). The overall percentage of participants with any treatment-emergent adverse events was similar between the GL Glargine (80.1%) and Lantus® (81.6%) treatment groups. CONCLUSIONS: GL Glargine was similar to Lantus® in terms of immunogenicity, efficacy, and safety, based on the current study.

Evaluating the global impact of low physical activity on type 2 diabetes: Insights from the global burden of disease 2019 study.

AIM: We aimed to assess the global implications of low physical activity (LPA) on type 2 diabetes mellitus (T2DM) by utilizing data from the Global Burden of Disease (GBD) 2019. METHODS: The analysis was conducted by examining the age-standardized disability-adjusted life years (DALYs) rates over a 30-year period. To assess the trends, we utilized estimated annual percentage changes (EAPCs). RESULTS: The study revealed a notable increase in the burden of DALYs attributable to T2DM resulting from LPA, with an EAPC of 0.84 (95% confidence interval 0.78-0.89). Among the regions examined, Oceania showed the highest burden, whereas Eastern Europe exhibited the lowest burden. Specifically, within the Central Asia region, a considerable increase in T2DM-LPA DALYs was observed, with an EAPC of 3.18 (95% confidence interval 3.01-3.36). The burden associated with T2DM-LPA DALYs was found to be similar between genders and increased across all age groups, peaking in the 80-84 years. Furthermore, there was a clear association between the socio-demographic index (SDI) and the age-standardized DALYs rate. Regions categorized as low-middle and middle SDI experienced a substantial rise in burden. CONCLUSION: This study highlights a substantial increase in the T2DM-LPA DALYs in low-middle and middle SDI regions, as well as among individuals aged 80-84 years. These findings emphasize the importance of implementing comprehensive global health interventions that promote physical activity, particularly targeting high-risk populations and regions.

Effect of type 2 diabetes on cardiac arrhythmias in patients with obstructive hypertrophic cardiomyopathy.

AIMS: Type 2 diabetes (T2D), a prevalent cardiovascular disease, is linked with cardiac arrhythmias such as atrial fibrillation (AF) and ventricular arrhythmia. This study evaluated T2D's impact on these arrhythmias in patients with obstructive hypertrophic cardiomyopathy (OHCM). METHODS AND MATERIALS: We retrospectively analyzed the data of 75 patients with OHCM and T2D from two medical centers in China from 2011 to 2020. A propensity score-matched cohort of 150 patients without T2D was also analyzed. RESULTS: Altogether, 225 patients were included. The prevalence of supraventricular tachycardia (SVT), AF, and non-sustained ventricular tachycardia (NSVT) was higher in patients with HCM and T2D than in those without T2D. Multivariate logistic regression showed T2D as an independent risk factor for SVT (odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.01-3.58, P = 0.04), AF (OR = 2.68, 95% CI = 1.27-5.67, P = 0.01), and NSVT (OR = 2.18, 95% CI = 1.04-4.57, P = 0.04). Further analysis identified fasting glucose and glycosylated hemoglobin levels as independent risk factors for AF and NSVT in patients with T2D. CONCLUSIONS: T2D independently increases the risk of cardiac arrhythmias (SVT, AF, NSVT) in OHCM patients. Furthermore, fasting glucose and glycosylated hemoglobin levels independently heighten AF and NSVT risk in OHCM patients with T2D.