We aimed to determine whether diabetes complications, such as kidney disease that may impair acid-base buffering capacity, independently predict the risk of subsequent diabetic ketoacidosis (DKA).

We accessed previously collected 34-year data from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study through public data access. Multivariable Cox proportional hazards models with time-varying exposures and covariates were used to examine the associations of macrovascular disease and early and late stages of neuropathy, nephropathy, and retinopathy, with subsequent DKA occurrence as the outcome.

Of 1,441 participants, 297 experienced 488 DKA events over follow-up. Major adverse cardiovascular events [hazard ratio (HR) 3.16, 95% CI 1.57-6.35, P = 0.001] and late-stage neuropathy, which comprised serious foot ulcer or amputation (HR 1.59, 95% CI 1.04-2.45, P = 0.03) were independently associated with higher DKA risk. Higher risk was also associated with shorter diabetes duration (HR 0.76, 95% CI 0.64-0.91, P = 0.002), female sex (HR 2.04, 95% CI 1.56-2.67, P < 0.001), current insulin pump use (HR 3.04, 95% CI 2.29-4.02, P < 0.001), higher time-updated HbA1c (per additional 1%: HR 1.39, 95% CI 1.29-1.50, P < 0.001), and higher current insulin dose (per 1 additional unit/kg/day: HR 2.32, 95% CI 1.62-3.33, P < 0.001).

A major cardiovascular event, foot ulcer, or amputation confers the greatest risk of future DKA independent of previously recognized risk factors, implying a need to target patients with these events for DKA prevention interventions, such as self-management skills for metabolic control, management of depression, and DKA education.

Diabetes mellitus is currently a priority health issue worldwide, but existing therapies suffer from insufficient donors, inability to provide glucose-dependent endogenous insulin secretion, transplantation risks, and immune rejection. Especially, reported engineered cells are mostly promoter-induced glucose-independent insulin producing cells. Here we constructed a closed-loop of insulin secretion with glucose-dependent IRES to achieve glucose-sensitive endogenous insulin secretion. Those cells successfully reversed hyperglycemia in diabetic mice for at least 60 days after transplantation without any significant immune rejection, demonstrating that our constructed engineered cellular grafts have good biocompatibility. Our findings hold great promise in the field of diabetes treatment and provide a new, glucose-dependent genetic engineering approach to insulin production, which is expected to solve many of the current problems faced in the clinical treatment of diabetes mellitus.

This participant-level exploratory analysis assessed the continuous time spent in glycaemic control and/or with sustained weight reductions with tirzepatide treatment in participants with type 2 diabetes (T2D) from the SURPASS programme.

Participants (N = 6246) from SURPASS 1-5 were randomized to once weekly tirzepatide (5, 10 or 15 mg) or comparator (once weekly placebo, once weekly semaglutide 1 mg, insulin degludec or insulin glargine). Continuous time spent with HbA1c < 7.0% (53 mmol/mol), ≤6.5% (48 mmol/mol) and ≥5% body weight reduction and combined HbA1c ≤ 6.5% (48 mmol/mol) with a ≥5% body weight reduction were assessed through 40 weeks (SURPASS-1, -2, and -5) or 52 weeks (SURPASS-3 and -4). The non-parametric Wilcoxon rank sum test was used to compare the median duration of continuous time spent in control, and logistic regression was used to analyse the proportion of participants achieving glycaemic control and body weight reduction at any time points or at the end of the primary study period.

Median time spent with HbA1c < 7.0% (53 mmol/mol) was 80% (tirzepatide) versus 70% (semaglutide) and 0% (placebo) of the treatment duration in 40-week studies, and 77%-85% (tirzepatide) versus 62% (insulin degludec) and 23% (insulin glargine) of the treatment duration in 52-week studies (p < 0.001). Time spent with HbA1c < 7.0% (53 mmol/mol) was generally similar across all tirzepatide doses in each study. Dose-dependent increases in time spent with ≥5% body weight reduction were observed with tirzepatide (median time spent: 20%-77% with tirzepatide versus 25% with semaglutide 1 mg) (p < 0.001). Tirzepatide-treated participants experienced longer time spent with HbA1c ≤ 6.5% (48 mmol/mol) and ≥5% body weight reduction versus semaglutide (median: 35%-60% vs. 7%) (p < 0.001).

In this post hoc analysis, people with T2D experienced substantially longer continuous time in glycaemic control and more sustained body weight reductions with tirzepatide versus placebo and active comparators.

This article discusses the evolving definitions of transient ischemic attack and minor strokes, highlighting the shared risk factors and the similarities in approach and early management. It emphasizes the importance of early identification and basic workup for these patients, as well as the most effective early antithrombotic therapies to date. The article also emphasizes the significance of controlling risk factors and concludes with a discussion of treatment strategies based on specific stroke etiologies.

When administered in early type 2 diabetes (T2DM), the strategy of 'induction' with short-term intensive insulin therapy (IIT) followed by 'maintenance' with metformin thereafter can yield outstanding glycaemic control, with some patients achieving A1c in the normal range of its assay. We thus sought to identify determinants of sustained normalisation of A1c in response to this treatment strategy.

In this study, adults with T2DM of mean duration 1.7 ± 1.4 years received induction IIT (glargine, lispro) for 3 weeks, followed by metformin maintenance either with or without periodic 2-week courses of IIT every 3 months for 2 years. Sustained glycaemic normalisation was defined by A1c <6.0% at 2 years.

Of 101 participants, 26 achieved A1c <6.0% at 2 years. At baseline, these individuals had lower A1c and fasting glucose than the other participants, along with better beta-cell function. During maintenance therapy from 3 weeks to 2 years, they had greater reduction of adiposity (body mass index: p = 0.02; waist circumference: p = 0.02), hepatic insulin resistance (HOMA-IR: p = 0.02) and ALT (p = 0.005), coupled with relative stabilisation of beta-cell function and glycaemia. On logistic regression analyses, significant independent predictors of normalisation of A1c at 2 years were baseline A1c (adjusted odds ratio [aOR] = 0.01 [95% CI 0.001-0.16], p = 0.001) and the changes in waist circumference (aOR = 0.77 [0.63-0.94], p = 0.012) and ALT (aOR = 0.90 [0.82-0.98], p = 0.019) during maintenance therapy from 3 weeks to 2 years.

While lower baseline A1c and greater reduction in central adiposity predicted A1c <6.0% at 2 years as anticipated, the emergence of greater reduction in ALT as a concomitant determinant highlights the role of the liver in the achievement of sustained glycaemic normalisation.

Children with type 1 diabetes have an increased risk of macrovascular complications. This study used ultra-high frequency ultrasound (UHFUS), enabling differentiation of intima thickness (IT), and media thickness (MT) in peripheral arteries, to examine early peripheral arterial changes in children with type 1 diabetes (CWD).

This cross-sectional and case-control study performed at the Queen Silvia Children's Hospital, Gothenburg, Sweden included CWD, aged 6-15.99 y/o, diabetes duration ≥5 years, compared to age and sex matched healthy controls. Exclusion criteria included other medical conditions or treatments besides insulin, abnormal examination findings or inability to handle extensive examinations. UHFUS measurements from the radial, dorsal pedal (DP), and carotid arteries as well as blood samples, blood pressure (BP)- and BMI z-score were collected from all study participants, and glucometrics from CWD.

Study inclusion was performed during 02/25/2019-06/28/2022, and a total of 50 CWD, and 41 healthy controls were included in the study. Of these, five CWD and four healthy controls were excluded, resulting in 45 (22 girls (49%), 23 boys (51%)) CWD (12.0 (2.3) y/o) and 37 (19 girls (51%), 18 boys (49%)) healthy controls (11.3 (2.5) y/o) included in data analysis. CWD had a mean HbA1c of 6.6% (48.1 mmol/mol), higher DBP z-scores (p = 0.019), DP IT, DP intima-media thickness (IMT), and radial IT compared with controls (p = 0.003, p = 0.008, and p = 0.002, respectively). Carotid IT was correlated with time in range (r = -0.47, p = 0.014), time in tight range (r = -0.64, p < 0.001), and glucose variability (r = 0.40, p = 0.004) in CWD. Time in tight range and longitudinal HbA1c were the strongest determinants for carotid IT in CWD, and type 1 diabetes diagnosis was the strongest determinant for IT across all arteries.

Children with well-regulated type 1 diabetes show early vascular changes in radial and DP arteries. Regression analyses indicate significant links between IT and hyperglycaemia and type 1 diabetes diagnosis respectively, indicating that structural arterial changes start in the intima. Our findings further emphasise increased time in normoglycemia as the most crucial action to prevent cardiovascular complications in type 1 diabetes. Additional larger studies are needed to confirm and further interpret the meaning of these results.

ALF-agreement, Child Diabetes Foundation, Swedish Diabetes Foundation, and the Sahlgrenska University Hospital Foundations.

Vascular endothelium is integral to the regulation of vascular homeostasis and maintenance of normal arterial function in healthy individuals. Endothelial dysfunction is a significant contributor to the advancement of atherosclerosis, which can precipitate cardiovascular complications. A notable correlation exists between diabetes and endothelial dysfunction, wherein chronic hyperglycemia and acute fluctuations in glucose levels exacerbate oxidative stress. This results in diminished nitric oxide synthesis and heightened production of endothelin-1, ultimately leading to endothelial impairment. In clinical settings, it is imperative to implement appropriate therapeutic strategies aimed at enhancing endothelial function to prevent and manage diabetes-associated vascular complications. Various antidiabetic agents, including insulin, GLP-1 receptor agonists, sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, α-glucosidase inhibitors, thiazolidinediones (TZDs), and metformin, are effective in mitigating blood glucose variability and improving insulin sensitivity by lowering postprandial glucose levels. Additionally, traditional Chinese medicinal compounds, such as turmeric extract, resveratrol, matrine alkaloids, tanshinone, puerarin, tanshinol, paeonol, astragaloside, berberine, and quercetin, exhibit hypoglycemic properties and enhance vascular function through diverse mechanisms. Consequently, larger randomized controlled trials involving both pharmacological and herbal interventions are essential to elucidate their impact on endothelial dysfunction in patients with diabetes. This article aims to explore a comprehensive approach to the treatment of diabetic endothelial dysfunction based on an understanding of its pathophysiology.

Since the arrival of continuous glucose monitoring (CGM), the relationship between the glucose management indicator (GMI) and HbA1c has been a topic of considerable interest in diabetes research. This study aims to explore the association between the GMI/HbA1c ratio and the presence of preclinical carotid atherosclerosis in type 1 diabetes (T1D).

Individuals with T1D and no prior history of cardiovascular disease were recruited from two centers. Carotid ultrasonography was performed using a standardized protocol and carotid plaques were defined as intima-media thickness ≥ 1.5 mm. CGM-derived data were collected from a 14-day report. A GMI/HbA1c ratio < 0.90 was selected to identify "fast-glycator" phenotype.

A total of 584 participants were included (319 women, 54.6%), with a mean age of 48.8 ± 10.7 years and a mean diabetes duration of 27.5 ± 11.4 years. Carotid plaques were present in 231 subjects (39.6%). Approximately 43.7% and 13.4% of participants showed absolute differences of ≥ 0.5 and ≥ 1.0 between 14-day GMI and HbA1c, respectively. Among patients ≥ 48 years, the fast-glycator phenotype was independently associated with presence of plaques (OR 2.27, 95%CI: 1.06-4.87), even after adjusting for non-specific and T1D-specific risk factors and statin treatment. No significant association was observed in younger subjects (p for interaction < 0.05).

Fast-glycator phenotype is independently associated with atherosclerosis in T1D individuals aged ≥ 48 years, suggesting an age-related increase in the glycation risk. These findings highlight the potential of the GMI/HbA1c ratio for cardiovascular risk stratification in this population.

Patients with type 1 diabetes (DM1), even in the setting of adequate glycaemic control, have an excess risk for developing cardiovascular disease. Residual insulin secretion (RIS), measured by detectable C-peptide levels in patients with DM1, might protect against diabetes-related complications. This study aimed to examine the relationship between residual insulin secretion and prognostic markers of cardiovascular complications in patients with DM1.

A total of 137 patients with DM1 were included in this analysis. They were of young age (<45 years), with an established diagnosis of over two years before the study entry and without a history of cardiovascular complications. All patients underwent complete clinical and laboratory evaluation. A c-peptide measurement of ≥0.05 ng/ml was used to identify the presence of RIS. Pulse wave velocity (PWV), cardiac autonomic function assessed both at rest, by total power of heart rate variability and dynamically, by the expiration to inspiration (e/i) index, albumin to creatinine ratio (ACR), and high sensitivity CRP (hs-CRP) were used as predictive biomarkers of cardiovascular complications.

Female participants represented 63.5% of the population [mean age: 29.7 (±8.1) years, mean HbA1c: 7.6% (±1.4), median diabetes duration:15 (10-21) years, median age at diabetes diagnosis: 13 (8-17) years]]. The median value of fasting c-peptide was 0.04 (0.03-0.05) ng/ml, and RIS was detected in 32 patients (23.4%). Patients with RIS had a shorter diabetes duration, an older age at diagnosis and a lower BMI, while no significant association was found between residual c-peptide and age or HbA1c. RIS was significantly associated with lower PWV values [8.1 m/s² (7-8.7) vs 9.2 m/s² (7.8-10.1), p <0,001], higher total power values [1124 Hz (600-3277) vs 577 Hz (207-2091), p <0,001], and higher E/I measurements [1.4 (1.2-1.5) vs. 1.3 (1.2-1.4), p=0.01]. No significant association was noted between RIS and either ACR or hs-CRP. In multivariable linear regression analysis, the association between RIS and lower PWV values remained significant (p= 0.007) regardless of age, sex, diabetes duration or age of diagnosis, blood pressure and BMI. Similarly, residual insulin secretion retained a significant independent association with total power (p= 0.032) and E/I (p=0.045).

In young patients with DM1, free of macrovascular complications, residual insulin secretion is independently associated with more favorable prognostic markers of subclinical atherosclerosis and cardiac autonomic function.

This study aimed to investigate the association between glucose metrics and diabetic retinopathy in type 1 diabetes (T1D) patients using flash continuous glucose monitoring (FGM) systems, including those maintaining glycated hemoglobin (HbA1c) within the target range.

We conducted a cross-sectional study involving 1070 T1D patients utilizing FGM systems. Data on clinical, anthropometric, and socioeconomic characteristics were collected and retinopathy was classified based on international standards.

Patients' mean age was 47.6 ± 15.0 years, with 49.4% of them being females. Within the cohort, 24.8% of patients presented some form of retinopathy. In the analysis involving the entire sample of subjects, male gender (OR = 1.51, p = 0.027), Time Above Range (TAR) > 250 mg/dL (OR = 1.07, p = 0.025), duration of diabetes (OR = 1.09, p < 0.001), smoking (OR = 2.30, p < 0.001), and history of ischemic stroke (OR = 5.59, p = 0.025) were associated with diabetic retinopathy. No association was observed between the coefficient of variation and diabetic retinopathy (p = 0.934). In patients with HbA1c < 7%, the highest quartile of TAR > 250 was independently linked to diabetic retinopathy (OR = 8.32, p = 0.040), in addition to smoking (OR = 2.90, p = 0.031), duration of diabetes (OR = 1.09, p < 0.001), and hypertension (OR = 2.35, p = 0.040).

TAR > 250 mg/dL significantly emerges as a modifiable factor associated with diabetic retinopathy, even among those patients maintaining recommended HbA1c levels. Understanding glucose metrics is crucial for tailoring treatment strategies for T1D patients.

Intraindividual body weight variability (BWV), that is, the degree of weight fluctuations over time, is associated with an increased risk of cardiovascular diseases (CVDs) in multiple settings. The impact of BWV on cardiovascular risk in type 1 diabetes (T1D) remains unclear, despite the issues relative to weight management in individuals with this condition.

Using data from the Swedish National Diabetes Register, we identified individuals with T1D and without CVD at baseline with at least three measurements of body weight taken over three consecutive years. We estimated BWV as quartiles of the standard deviation of weight measures and explored its longitudinal association with the incidence of CVD during a 12.7 ± 4.6 year follow-up through adjusted Cox regression models. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke and all-cause mortality. We modelled the function of risk in relation to the magnitude of BWV, testing also whether weight trends, that is, increasing, stable or decreasing, age, sex and glycaemic control modified the association between BWV and the outcome.

Among the 36 333 individuals with T1D in the register, we identified 19 373 individuals with at least three measures of body weight and without CVD at baseline. Participants with the highest BWV had a 42% increased risk of reaching the primary endpoint compared to those with the lowest BWV (hazard ratio [HR] = 1.42, 95% confidence interval [CI]: 1.24-1.62). In addition, high BWV was significantly associated with a 51% increased risk of all-cause mortality (HR = 1.51, 95% CI: 1.28-1.78), a 37% increased risk of peripheral artery disease (HR = 1.37, 95% CI: 1.06-1.77) and a 55% increased risk of hospitalization for heart failure (HR = 1.55, 95% CI: 1.20-2.01). BWV showed a quasi-linear association with the primary endpoint. No interaction was observed when comparing subgroups for weight trends, sex or degree of glycaemic control. In the subgroup of elderly individuals, the association of BWV with the primary endpoint was no longer significant.

High BWV is associated with an increased risk of CVD and all-cause mortality in individuals with T1D, independently of canonical risk factors. Weight trends, sex and glycaemic control do not modify such association while older age attenuates it.

Diabetic vascular aging is driven by macrophage senescence, which propagates senescence-associated secretory phenotypes (SASP), exacerbating vascular dysfunction. This study utilized a type 2 diabetes mellitus (T2DM) mouse model induced by streptozotocin injection and a high-fat diet to investigate the role of STING in macrophage senescence. Vascular aging markers and senescent macrophages were assessed in vivo, while in vitro, high glucose treatment induced macrophage senescence, enhancing senescence in co-cultured vascular smooth muscle cells. Mechanistic studies revealed that STING activation inhibits autophagy by phosphorylating ULK1 at S757, accelerating senescence. Pharmacological modulation showed that the STING inhibitor H-151 alleviates, while the agonist DMXAA enhances, senescence. These findings highlight the STING-autophagy axis as a critical driver of macrophage senescence, offering insights into the molecular mechanisms of diabetic vascular aging and identifying potential therapeutic targets to mitigate vascular complications in diabetes.

Diabetes is associated with increased atherosclerotic cardiovascular disease (ASCVD) risk, a leading cause of morbidity and mortality. Disordered lipid metabolism is a major contributor to ASCVD risk in diabetes. Dyslipidemia in type 2 diabetes is characterized by hypertriglyceridemia, low HDL cholesterol and the presence of small, dense LDL particles. Statins have demonstrated longstanding benefit for reducing ASCVD risk in individuals with diabetes. Newer agents for add-on therapies to statins are now available for additional cardiovascular risk reduction. In this clinical overview, we review the pathogenesis of dyslipidemia in both types 1 and 2 diabetes and provide an update on the management of lipids in the individual with diabetes. We discuss the importance of appropriate risk stratification, individualized treatment selection, and the need to avoid therapy inertia to mitigate cardiovascular risk. We will also address lipid-related effects of glycemic lowering therapies.

Efforts to improve glycemic control in type 1 diabetes are ongoing. We performed a randomized, double-blind, crossover trial to assess semaglutide as adjunct to automated insulin delivery therapy in adults with type 1 diabetes. At each intervention, participants were titrated up to 1 mg or the maximum tolerated dose of semaglutide or placebo over 11 weeks, followed by the use of an automated insulin delivery system for 4 weeks. The primary outcome was the percentage of time spent in the target glucose range of 3.9-10.0 mmol l-1 during the last 4 weeks of each intervention. Twenty-eight participants were randomized and 24 completed the trial. The primary endpoint was met. Compared to placebo, semaglutide increased time in the target range by a mean 4.8 (s.d. = 7.6) percentage points (P = 0.006), without increasing the time spent below 3.9 mmol l-1 (P = 0.19) or below 3.0 mmol l-1 (P = 0.65). While no diabetic ketoacidosis or severe hypoglycemia occurred during any of the interventions, there were two episodes of recurrent euglycemic ketosis without acidosis during semaglutide use. We conclude that semaglutide improves glycemic control with automated insulin delivery compared to placebo. ClinicalTrials.gov registration: NCT05205928.

The natural history of type 1 diabetes (T1D) evolves from stage 1 (islet autoimmunity with normoglycemia; ICD-10 diagnostic code E10.A1) to stage 2 (autoimmunity with dysglycemia; E10.A2) and subsequent clinical stage 3 (overt hyperglycemia), which is commonly the first time of referral. Autoantibody testing can diagnose T1D at its preclinical stages 1-2 and lead to earlier initiation of care, particularly for first-degree relatives of people living with T1D, who are at higher genetic risk. Preclinical T1D screening and monitoring aims to avoid inaugural ketoacidosis and prolong preservation of endogenous insulin secretion, thereby improving glycemic control and reducing long-term morbidity. Moreover, early management can help coping with T1D and correct modifiable risk factors (obesity, sedentary lifestyle). New treatments currently under clinical deployment or trials also offer the possibility of delaying clinical progression. All these arguments lead to the proposition of a national screening and care pathway open to interested first-degree relatives. This pathway represents a new expertise to acquire for healthcare professionals. By adapting international consensus guidance to the French specificities, the proposed screening strategy involves testing for ≥ 2 autoantibodies (among IAA, anti-GAD, anti-IA-2) in relatives aged 2-45 years. Negative screening (∼95 % of cases) should be repeated every 4 years until the age of 12. A management workflow is proposed for relatives screening positive (∼5 % of cases), with immuno-metabolic monitoring by autoantibody testing, OGTT, glycemia and/or HbA1c of variable frequency, depending on T1D stage, age, patient preference and available resources, as well as the definition of expert centers for preclinical T1D.

Several epidemiological studies have appreciated the impact of "duration" and "level" of hyperglycemia on the initiation and development of chronic complications of diabetes. However, glycemic profiles could not fully explain the presence/absence and severity of diabetic complications. Genetic issues and concepts of "hyperglycemic memory" have been introduced as additional influential factors involved in the pathobiology of late complications of diabetes. In the extended phase of significant diabetes randomized, controlled clinical trials, including DCCT/EDIC and UKPDS, studies have concluded that the quality of glycemic or metabolic control at the early time around the diabetes onset could maintain its protective or detrimental impact throughout the following diabetes course. There is no reliable indication of the mechanism by which the transient exposure to a given glucose concentration level could evoke a consistent cellular response at target tissues at the molecular levels. Some biological phenomena, such as the production and the concentration of advanced glycation end products (AGEs), reactive oxygen species (ROS) and protein kinase C (PKC) pathway activations, epigenetic changes, and finally, the miRNAs-mediated pathways, may be accountable for the development of hyperglycemic memory. This work summarizes evidence from previous experiments that may substantiate the hyperglycemic memory soundness by its justification in molecular terms.

The extent of the performance and utility of scores for the risk of cardiovascular disease (CVD) in persons with type 1 diabetes (T1DM) largely remains unclear.

The purpose of this study was to synthesize data on the performance of CVD risk scores in people living with T1DM.

This study is a systematic review and meta-analysis. PubMed and EMBASE were searched through December 31, 2023. The included studies: 1) were retrospective, prospective, or cross-sectional in design; 2) included persons with T1DM; 3) assessed CVD outcomes; and 4) had data on at least on CVD risk score. Measures of calibration and discrimination qualitatively summarized. Measures of discrimination were combined using random-effects models stratified by type of risk model.

In a meta-analysis of observational studies of CVD risk scores in T1DM individuals, including 11 studies and 73,664 participants (mean age of 34 years, mainly White individuals and male [55%]), we evaluated 12 CVD risk prediction models (7 T1DM-specific, 1 type 2 diabetes-specific, and 4 general population models). Most risk scores had a moderate to excellent discrimination (C-statistic: 0.73-0.85) and predicted CVD risk well when compared to actual clinical events. CVD risk scores specifically developed in T1DM individuals exhibited a higher discriminative performance-pooled C-statistic of 0.81 vs 0.75 for risk scores developed in the general population or those with type 2 diabetes and also showed a better calibration.

Among individuals with T1DM, CVD risk models had a moderate to excellent discrimination, with a better discrimination and accuracy for T1DM-specific scores.

Background and Objectives: Insulin resistance (IR) is the most important factor involved in the pathogenesis of type 2 diabetes but may also develop in type 1 diabetes (T1DM). Developing IR in patients with T1DM may generate a burden in achieving glycemic targets and may deteriorate the overall prognosis. This review aims to describe the pathogenesis of IR in T1DM, summarize the common associations of IR with other conditions in patients with T1DM, describe the consequences of developing IR in these patients, and present the interventions that target IR in people with T1DM. Results: The occurrence of IR in T1DM is multifactorial; however, it is frequently linked to overweight or obesity and sedentary lifestyle. Besides impairments in glycemic control and increased insulin requirements, the presence of IR is associated with an increased cardiovascular risk in patients with T1DM. Considering that patients with T1DM are insulin-treated, IR may be evaluated only using surrogate biomarkers, the most frequently used being the estimated glucose disposal rate. The most important interventions that are shown to be feasible in improving insulin sensitivity in patients with T1DM are lifestyle optimizations, including nutrition therapy or physical activity and pharmacotherapy with metformin, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and thiazolidinediones. Conclusions: Targeting the improvement of IR in patients with T1DM is a key element in achieving optimal glycemic control, as well as improving the overall patient's prognosis besides glycemic control.

Cardiovascular disease (CVD) and diabetes mellitus are prominent public health concerns in Saudi Arabia owing to their increasingly high prevalence and burden. Based on this, the Saudi Heart Association (SHA) set out to develop an official position statement on CVD and diabetes mellitus, with a focus on the prevention and management of these conditions and relevant special populations in the context of Saudi Arabia.

A multidisciplinary panel of experts met under the auspices of the SHA in a series of meetings to review and discuss available evidence on the prevention and management of comorbid CVD and diabetes mellitus. Specialized subcommittees reviewed the data and offered context-specific recommendations (taking into account Saudi population characteristics, local healthcare system, available resources and medical expertise), which were later approved by the full expert panel.

The prevalence of diabetes mellitus and CVD is alarming in the Saudi Arabian population. Diabetes mellitus and CVD are interconnected on several levels, including cellular and molecular events as well as epigenetic and genetic mechanisms. Screening for CVD is a priority for patients with diabetes and concomitant risk factors. The expert panel also recommends aggressive management of high blood pressure and dyslipidemia in addition to lifestyle changes and achieving glycemic targets for the prevention of CVD in patients with diabetes. Some glucose-lowering drug classes, namely SGLT2-inhibitors and GLP-1 receptor agonists, offer significant benefits on the level of cardiovascular risk reduction and are thus a powerful addition to the clinical management armamentarium in CVD and diabetes. Special consideration is also advised for patient populations with distinct clinical presentation and needs, such as coronary artery disease, heart failure, and chronic kidney disease, among others.

Metabolic abnormalities such as central obesity, insulin resistance, dyslipidaemia and hypertension, often referred to as 'the metabolic syndrome' (or 'combined metabolic abnormalities'), are increasingly being identified in people living with type 1 diabetes, accelerating the risk for CVD. As a result, in recent years, treatment in people living with type 1 diabetes has shifted to improving overall metabolic health rather than glucose control alone. In Belgium, diabetes care for people living with type 1 diabetes is centrally organised. The Initiative for Quality Improvement and Epidemiology in Diabetes, imposed by the Belgian health insurance system, has systematically collected data from patients on intensive insulin therapy treated in all 101 diabetes clinics in Belgium since 2001. The aim of this real-world study is to describe the evolution of treatment and metabolic health, including the prevalence of obesity and combined metabolic abnormalities, in people living with type 1 diabetes over the past 20 years, and to compare the treatment and prevalence of complications between those with and without combined metabolic abnormalities.

We analysed data on adults (≥16 years old) living with type 1 diabetes, who were diagnosed at age ≤45 years and who had a diabetes duration ≥1 year, collected between 2001 and 2022. The evolution of HbA1c, BMI, LDL-cholesterol, systolic BP, lipid-lowering therapy and antihypertensive therapy over time was analysed. The prevalence of individual and multiple metabolic abnormalities according to various definitions of the metabolic syndrome/combined metabolic abnormalities was analysed, and the association between combined metabolic abnormalities and metabolic health indicators, complications and treatment was investigated in the 2022 data.

The final dataset consisted of 26,791 registrations of adults living with type 1 diabetes collected between 2001 and 2022. Although glycaemic and lipid control generally improved over time, the prevalence of obesity strongly increased (12.1% in 2001 vs 21.7% in 2022, p<0.0001), as did the presence of combined metabolic abnormalities (WHO criteria: 26.9% in 2001 vs 42.9% in 2022 in women, p<0.0001; 30.4% in 2001 vs 52.1% in 2022 in men, p<0.0001; WHO criteria without albuminuria: 22.3% in 2001 vs 40.6% in 2022 in women, p<0.0001; 25.1% in 2001 vs 49.2% in 2022 in men, p<0.0001; NCEP-ATPIII criteria: 39.9% in 2005 vs 57.2% in 2022 in women, p<0.0001; 40.8% in 2005 vs 60.9% in 2022 in men, p<0.0001; IDF criteria: 43.9% in 2005 vs 59.3% in 2022 in women, p<0.001; 33.7% in 2005 vs 50.0% in 2022 in men, p<0.0001). People with combined metabolic abnormalities had higher glucose levels compared to those without combined metabolic abnormalities (HbA1c >58 mmol in men: 48.9% vs 36.9%; HbA1c >58 mmol in women: 53.3% vs 41.1%, p<0.0001). People with combined metabolic abnormalities were more often treated with adjunct therapies such as metformin, sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists. In both men and women, the presence of combined metabolic abnormalities was strongly related to the presence of eye complications, peripheral neuropathy, chronic kidney disease and CVD, corrected for age, diabetes duration and HbA1c.

Overweight, obesity and combined metabolic abnormalities are increasingly being identified in people living with type 1 diabetes, further accelerating the risk of microvascular and macrovascular complications. Early identification of the presence of combined metabolic abnormalities should enable therapeutic interventions to be modified towards multifactorial approaches, with attention to education on avoidance of overweight (e.g. dietary counselling) in addition to strict glycaemic control and intensification of use of antihypertensive agents and statins. Use of adjunct therapies in this population as a tool should be explored more thoroughly to reduce risk of complications.

To assess the effect of comorbidities, risk classification for chronic kidney disease (CKD) according to albuminuria and eGFR, HbA1c and LDL-cholesterol levels on all-cause mortality in patients with type 1 diabetes (DM1).

The study included all 45,801 DM1 patients from the Finnish Diabetes Registry during 2018-2022. Mortality of patients with DM1 was compared with mortality in non-diabetic population in Finland by estimating standardized mortality rates (SMRs). Poisson regression model was used to estimate the effect of risk factors on the SMR.

A total of 2469 patients died during follow-up. SMR for the total cohort was 1.84 (95 % CI 1.77-1.92) peaking at the age of 30-49 years. The coverage of HbA1c values was 98 %, that of LDL-cholesterol 94 %, and U-ACR and eGFR 80 %. In a multivariate analysis, assessing the effect on mortality, the rate ratio for end-stage renal disease was 2.66, cardiovascular diseases 1.92, mental and behavioural disorders 1.64, foot complications 1.51, high or very high risk for CKD 3.64, LDL-cholesterol ≥2.6 mmol/l 1.33, and HbA1c ≥8 % (64 mmol/mol) 1.27.

There's substantial excess mortality due to DM1 in Finland. Interventions should focus on addressing both renal and cardiovascular risk factors but also pay more attention to mental health.

In an aging population, the prevalence and burden of diabetes mellitus, diabetic retinopathy, and vision-threatening diabetic macular edema (DME) are only expected to rise around the world. Similarly to other complications of diabetes mellitus, DME requires long-term management. This article aims to review the current challenges associated with the long-term management of DME, opportunities to improve outcomes for patients, and to develop a treat-to-target strategy based on macular morphology. At present, intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard of care for the management of DME; however, best-achievable vision outcomes with treatment are reliant on frequent injections and close monitoring, which are difficult to maintain in current clinical practice because of the burden this imposes on patients. Achieving and maintaining good vision with treatment are the most important factors for patients with DME. Landmark trials have shown that vision gains with anti-VEGF therapy are typically accompanied by anatomical improvements (e.g., reductions in retinal thickness); therefore, multimodal imaging measures of macular morphology are often used in patients with DME to guide real-world treatment decisions. We would like to propose a hypothetical treat-to-target algorithm to guide physicians on treatment strategies for the long-term management of DME. Alternative measures of retinal fluid (e.g., persistence, stability, location) may be stronger predictors of visual acuity in DME, although further research is required to confirm whether alternate quantifiable biomarkers such as subretinal fluid and intraretinal fluid volumes can be used as a biomarker of clinical improvement. Identifying novel biomarkers and treatments that target neuroinflammation and neurodegeneration, improving patient-physician communication around treatment adherence, and using treat-to-target measures may help to ensure that the long-term benefits of treatment are realized.

Achieving an ideal glycemic control in children and adolescents with type 1 diabetes mellitus (T1DM) is both a difficult and challenging process. We aim to highlight the expected factors contributing to inadequate glycemic control in children and adolescents with T1DM in a sample of Iraqi children and adolescents.

This was a descriptive cross-sectional study that recruited 247 T1DM patients aged < 18 years & disease duration ≥ 1 year. Data collected included socio-demographic & clinical characteristics with recent HbA1c value. Each patient was examined for signs of puberty and any lipodystrophy at insulin injection sites. Factors studied using Independent-Samples T-Test, One way ANOVA & Multivariable logistic regression.

Of the 247 patients, 108 (43.7%) were males, and 139 (56.3%) were females. The mean & SD of the age of patients was 10.13 ± 3.85 years. The Mean & SD of the recent HbA1c level was 9.43 ± 2.56. HbA1c ≤ 7.5 was achieved in 27.1% of patients. Using Multivariable logistic regression to study the association between variable factors and inadequate glycemic control, showed a significant association with higher odds in terms of the older age of the patient, maternal illiteracy, presence of recurrent diabetic ketoacidosis (DKA) episodes, absence of carb counting, and presence of lipodystrophy. Higher HbA1c was also associated significantly with puberty, rural residency, poor socioeconomic status, DKA presentation, and using regular + NPH insulin regimen.

In the current study, inadequate glycemic control was induced by many factors, Strategies should be applied to control these factors to minimize the prospective risks of macro-vascular complications linked to T1DM in children & adolescents.

The online version contains supplementary material available at 10.1007/s40200-024-01442-2.

Since the introduction of insulin therapy, it has become apparent that type 1 diabetes (T1D) is accompanied by long-term microvascular and macrovascular complications. In the context of the many benefits of continuous glucose monitoring (CGM), there remain opportunities to study the large amount of data now available in order to maximise its potential in the endeavour to reduce the occurrence of diabetes tissue complications in the longer term.

Continuous glucose monitoring values were downloaded for 89 type 1 diabetes mellitus (T1D) individuals for up to 18 months from 2021 to 2023. Data for patient demographics was also taken from the patient record which included Sex, Date of Birth, and Date of Diagnosis. The recorded laboratory glycated haemoglobin (HbA1c) test results were also recorded. The glucose management index (GMI) was calculated from average glucose readings for 18 months using the formula GMI (%) = (0.82 - (Average glucose/100)). This was then adjusted to give GMI (mmol/mol) = 10.929 * (GMI (%) - 2.15). Average Glucose Fluctuation (AGF) was calculated by adding up the total absolute change value between all recorded results over 18 months and dividing by the number of results minus one. The % Above Critical Threshold (ACT) was calculated by summing the total number of occurrences for each result value. A cumulative 95% limit was then applied to identify the glucose value that only 5% of results exceeded in the overall population. Using this value, we estimated the percentage of total tests that were above the Critical Threshold (ACT).

The mean age of the participants was 42.6 years, and the mean duration of T1D was 18.4 years. A total of 3.22 million readings were analysed, yielding an average blood glucose level of 10.3 mmol/l and a GMI of 57.2 mmol/mol. There was a strong correlation between GMI and measured HbA1c (r2 = 0.82). However, there were patients who had an above-critical threshold (ACT) of 4-10% at a GMI of 60 mmol/mol or less. The percentage average value at the time of day (%AVTD) was applied to all blood glucose readings at each 15-min interval throughout the day, averaged over 18 months. The %AVTD of GMI (overall average 57.2 mmol/mol) increased after midday, dipped at 18:00, and peaked at 22:00. The %AVTD of AGF (overall average 0.60 mmol/l) showed higher change rates after 09:00 declining at the end of the day. The %AVTD of ACT peaked at 22:00, with those having the highest %ACT showing an additional peak at 15:00.

We have shown here that the percentage glucose results above 18 mmol/l (top 5% of distribution) increased exponentially above 54 mmol/mol HbA1c. The %AVTD is introduced as a useful measure. Our data indicate that over the 24-h period, improvement in metabolic control could be focussed on the afternoon and evening, when there are higher-than-average levels of GMI, a higher-than-average degree of glucose change, and higher-than-average risks of being above the critical threshold. In conclusion, a measure of glycaemic variation based on the amplitude of glucose change to a population mean could be used to provide valuable clinical insights into glucose change over a 24-h period.

Microvascular and macrovascular complications in type 1 diabetes (T1D) may be linked to endothelial stress due to glycaemic variability. Continuous glucose monitoring systems (CGMs) provide new opportunities to quantify this variability, utilising the amplitude of glucose change summated over time. The aim of this study was to examine whether this determination of glucose variability (GV) is associated with microvascular clinical sequelae.

Continuous glucose monitoring values were downloaded for 89 type 1 diabetes mellitus (T1D) individuals for up to 18 months from 2021 to 2023. Data for patient demographics was also taken from the patient record which included Sex, Date of Birth, and Date of Diagnosis. The recorded laboratory glycated haemoglobin (HbA1c) test results were also recorded. The glucose management index (GMI) was calculated from average glucose readings for 18 months using the formula GMI (%) = (0.82-(Average glucose/100)). This was then adjusted to give GMI (mmol/mol) = 10.929 * (GMI (%) - 2.15). Average Glucose Fluctuation (AGF) was calculated by adding up the total absolute change value between all recorded results over 18 months and dividing by the number of results minus one. The % Above Critical Threshold (ACT) was calculated by summing the total number of occurrences for each result value. A cumulative 95% limit was then applied to identify the glucose value that only 5% of results exceeded in the overall population. Using this value, we estimated the percentage of total tests that were above the Critical Threshold (ACT).

Results for the 89 individuals (44 men and 45 women) were analysed over 18 months. The mean age of participants was 43 years and the mean duration of diabetes was 18 years. A total of 3.22 million readings were analysed, giving an average of 10.3 mmol/L blood glucose. Those with the largest change in glucose from reading to reading, summated over time, showed the greatest change in eGFR of 3.12 ml/min/1.73 m2 (p = 0.007). People with a higher proportion of glucose readings > 18 mmol/L showed a fall in eGFR of 2.8 ml/min/1.73 m2 (p = 0.009) and experienced higher rates of sight-threatening retinopathy (44% of these individuals) (p = 0.01) as did 39% of individuals in the highest tertile of glucose levels (p = 0.008).

Those individuals with T1D in the highest tertile of reading-to-reading glucose change showed the greatest change in eGFR. Those with a higher proportion of glucose readings > 18 mmol/L also showed a fall in eGFR and experienced higher rates of sight-threatening retinopathy, as did people with higher mean glucose. Discussions with T1D individuals could reflect on how the percentage recorded glucose above a critical level and degree of change in glucose are important in avoiding future tissue complications.

Cardiovascular autonomic neuropathy (CAN) is an under-recognised yet highly prevalent microvascular complication of diabetes. CAN affects approximately 20% of people with diabetes, with recent studies highlighting the presence of CAN in prediabetes (impaired glucose tolerance and/or impaired fasting glucose), indicating early involvement of the autonomic nervous system. Understanding of the pathophysiology of CAN continues to evolve, with emerging evidence supporting a potential link between lipid metabolites, mitochondrial dysfunction and genetics. Recent advancements, such as streamlining CAN detection through wearable devices and monitoring of heart rate variability, present simplified and cost-effective approaches for early CAN detection. Further research on the optimal use of the extensive data provided by such devices is required. Despite the lack of specific pharmacological interventions targeting the underlying pathophysiology of autonomic neuropathy, several studies have suggested a favourable impact of newer glucose-lowering agents, such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, where there is a wealth of clinical trial data on the prevention of cardiovascular events. This review delves into recent developments in the area of CAN, with emphasis on practical guidance to recognise and manage this underdiagnosed condition, which significantly increases the risk of cardiovascular events and mortality in diabetes.

We assessed the impact of intermittently scanned continuous glucose monitoring (isCGM) compared with blood glucose monitoring (BGM) on rates of hospitalization for metabolic and vascular complications of diabetes and on HbA1c levels for adults with type 1 diabetes.

This retrospective study using data from the Swedish National Diabetes Register and the Swedish National Patient Register comprised adults with type 1 diabetes and an isCGM initiation date after 1 June 2017 and matched control individuals using BGM. Hospital admission rates were calculated per 100 person-years of follow-up.

We identified 11,822 adults with type 1 diabetes and an isCGM index date after 1 June 2017 and HbA1c baseline values 3-8 months prior to the index date. Compared with 3,007 BGM users, isCGM users had a significantly lower relative risk of hospitalization for hypoglycemia (0.32; 95% CI 0.14, 0.74), diabetic ketoacidosis (0.55; 0.35, 0.87), stroke (0.48; 0.37, 0.64), acute myocardial infarction (0.64; 0.46, 0.91), atrial fibrillation (0.59; 0.38, 0.94), heart failure (0.25; 0.16, 0.39), peripheral vascular disease (0.21; 0.07, 0.62), kidney disease (0.48; 0.35, 0.66), or hospitalization for any reason (0.32; 0.29, 0.35). Compared with BGM users, change in mean HbA1c for isCGM users was -0.30% (-3.3 mmol/mol) at 6 months and -0.24% (-2.6 mmol/mol) at 24 months (both P < 0.001).

This study shows that adults with type 1 diabetes in Sweden who initiate isCGM have significantly reduced hospitalization rates for acute diabetes events, kidney disease, and cardiovascular complications, along with improved glucose control, compared with BGM users.

To investigate the association of diabetes duration with cardiovascular disease (CVD) risk and to examine the relationship between lipid levels and CVD risk over the duration.

Using the Korean National Health Insurance Service Cohort database, we identified 2 359 243 subjects with type 2 diabetes aged ≥ 20 years in 2015 to 2016. Baseline lipid levels and diabetes duration were evaluated and followed up until December 2020 (mean follow-up, 3.9 years). Subjects were categorized according to diabetes duration (new-onset, < 5 years, 5-9 years, or ≥ 10 years). We analyzed the new-onset diabetes group with low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL as the reference group. The hazard ratios (HRs) and 95% CIs of myocardial infarction (MI) and ischemic stroke (IS) were estimated using a Cox proportional hazards model adjusted for potential confounders.

During follow-up, 45 883 cases of MI and 53 538 cases of IS were identified. The risk of MI or IS began to increase at LDL-C ≥ 160 mg/dL in the new-onset diabetes group, and at LDL-C ≥ 130 mg/dL in the group with diabetes duration < 5 years. Among subjects with diabetes duration of 5 to 9 years, LDL-C levels of 100-129 mg/dL, 130-159 mg/dL, and ≥ 160 mg/dL were significantly associated with the risk of MI (HR [95% CI] 1.13 [1.04-1.22], 1.28 [1.17-1.39], and 1.58 [1.42-1.76], respectively). MI risk in the diabetes duration ≥ 10 years group was increased by 16%, even in the LDL-C 70-99 mg/dL population (HR [95% CI] 1.16 [1.08-1.25]).

This population-based longitudinal study revealed that the LDL-C cutoff level for increasing the risk of CVD varied with diabetes duration and that the target LDL-C level should depend on the duration.

Aim: To examine the oral health of children and adolescents with and without diabetes mellitus. Background: Diabetes mellitus is the most common metabolic disease in childhood and demonstrates an increasing incidence. Many children live with gingivitis as a precursor to periodontitis. If left untreated, it can cause the development of periodontitis. The links between periodontitis and diabetes mellitus are known but have been little studied in the age group of children and adolescents. Materials and Methods: Clinical examination and collection of sulcus fluid from participants aged 5 to 21 years was performed. The following data were collected: demographic variables, caries prevalence, DMF-T, VPI, PUFA, salivary flow rate, HbA1c, PSI, and the concentration of IL-1β, IL-6, MMP-8, and TNF-α. Results: Patients with diabetes mellitus showed a significantly lower salivary flow rate with higher concentrations of MMP-8 and IL-1β. The data indicate that at this age, regular visits to the dentist are of great importance for the promotion of oral health in children and adolescents regardless of diabetes and that patients with diabetes mellitus in particular benefit from prevention, as they belong to the periodontitis risk group. Conclusions: Patients with low salivary flow rates and increased inflammatory mediators are high-risk patients for whom dental preventive measures play a major role.

To characterize and stratify health-related quality of life in individuals with type 1 diabetes (T1D) using body mass index (BMI) and clustering analysis.

Baseline data on individuals with T1D were pooled from two studies. A post hoc analysis of health-related quality of life, measured using the 36-item Short-Form questionnaire, was performed, referenced to the 2010 US general population. Descriptive statistics were presented for the pooled cohort and per BMI category. K-means clustering was performed. One-way analysis of variance was conducted to examine differences in clinical characteristics between clusters.

The pooled cohort consisted of 2256 individuals with T1D (age: 45.4 ± 15.0 years, BMI: 26.2 ± 4.6 kg/m2, diabetes duration: 22.7 ± 13.5 years). All quality-of-life domains were slightly lower than 50(the general population's mean), except for vitality. Individuals with a BMI ≥30 kg/m2 reported lower scores for bodily pain, physical functioning, general health, and vitality. A first cluster with a high and a second cluster with a low quality of life were identified, with significant differences in the mental (Cluster 1: 53.8 ± 6.8 vs. Cluster 2: 39.5 ± 10.7; p < 0.001) and physical component summary scores (Cluster 1: 49.6 ± 6.3 vs. Cluster 2: 35.2 ± 12.0; p < 0.001), which exceeded differences found between BMI categories.

In our population of people living with T1D, higher BMI may have adversely impacted physical domains of quality of life, but larger differences between the high- and low-quality-of-life cluster indicate that more factors play a role.

The real-world benefits of continuous glucose monitoring (CGM) in the broad type 2 diabetes (T2D) population are not well studied. Our study evaluated the impact of CGM use on health care resource utilization over 12 months in adults with T2D.

This retrospective cohort analysis used Optum's de-identified Market Clarity data of >79 million people to evaluate CGM use in people with T2D who were treated with non-insulin (NIT), basal insulin (BIT) and prandial insulin therapy (PIT). The primary outcomes were changes in all-cause hospitalizations, acute diabetes-related hospitalizations and acute diabetes-related emergency room visits during the 6- and 12-month post-index period following transition from blood glucose monitoring to CGM. A pre-specified subgroup analysis assessed glucose control and medication changes among people with T2D over 1 year.

The analysis included 74 679 adults with T2D (NIT; n = 25 269), (BIT; n = 16 264) and (PIT; n = 33 146). Significant reductions in all-cause hospitalizations, acute diabetes-related hospitalizations and acute diabetes-related emergency room visits were observed in the 6-month post-index period that were sustained during the 6-12 month post-index period (NIT, -10.1%, -31.0%, -30.7%; BIT, -13.9%, -47.6%, -28.2%; and PIT, -22.6%, -52.7%, -36.6%, respectively). A subgroup analysis of 6030 people showed mean glycated haemoglobin reductions at approximately 3 months, which were also sustained throughout the post-index period: NIT, -1.1 (0.05)%; BIT, -1.1 (0.06)%; and PIT, -0.9 (0.04)%, p < 0.0001.

CGM use in real-life across different therapeutic regimens in adults with T2D was associated with reductions in health care resource utilization with improved glucose control over 1 year.

We investigated whether a short period of tightly controlled low-carbohydrate diet (LCD) leads to higher time in range without increasing the associated risks in children and young people with diabetes (CYPwD).

Thirty-five (CYPwD) were recruited into this randomized controlled cross-over study (20 female; 20 CSII; age 14.5 ± 2.9 years; HbA1c 48.9 ± 9.4 mmol/mol). The interventions were five and five weeks of ready-made food box deliveries of isocaloric diets in random order: either LCD (94.5 ± 4.7 g/day) or recommended carbohydrate diet (RCD) (191 ± 19.2 g/day). The outcomes were continuous glucose monitoring parameters, anthropometric, laboratory and quality of life (QoL) data.

Time in range was significantly higher in the LCD than in the RCD period (77.1 % vs. 73.8 %, P=0.008). Times in hyperglycemia and average glycaemia were significantly lower in the LCD. There was no difference between the diets in time in hypoglycemia or glycemic variability. The subjects' body weight and BMI were significantly lower during the LCD. There was no significant difference in the LDL-cholesterol levels. No significant differences were observed in the self-assessed QoL.

Short-term LCD led to an improvement of glycemic parameters without increasing time in hypoglycemia, disturbing the lipid profile or negatively affecting the quality of life of CYPwD.

Patients with peripheral artery disease and generalized atherosclerosis are at high risk of cardiovascular and limb complications, affecting both quality of life and longevity. Lower limb atherosclerotic disease is associated with high cardiovascular morbidity and mortality and adequate management is founded on treatments involving patient-dependent factors, such as lifestyle changes, and physician-dependent factors, such as clinical treatment, endovascular treatment, or conventional surgery. Medical management of peripheral artery disease is multifaceted, and its most important elements are reduction of cholesterol level, antithrombotic therapy, control of arterial blood pressure, control of diabetes, and smoking cessation. Adhesion to this regime can reduce complications related to the limbs, such as chronic limb-threatening ischemia, that can result in amputation, and the systemic complications of atherosclerosis, such as stroke and myocardial infarction.

Metabolic memory (MM) is a major factor in the delayed wound healing observed in diabetic patients. While "Nocardia rubrum cell wall skeleton" (Nr-CWS) is utilized to enhance macrophage proliferation in immune diseases, its impact on MM wounds in diabetes is unclear. This study demonstrates that transient hyperglycemia leads to prolonged damage in vascular endothelial cells by decreasing METTL3 expression, leading to decreased RNA methylation and impaired cellular metabolism. Remarkably, Nr-CWS application increases METTL3 levels in these cells, facilitating the recovery of cell function. Further in vivo and in vitro analyses demonstrate that transient hyperglycemia-induced reduction in METTL3 hinders RNA methylation of the downstream gene Cds2, impacting mitochondrial function and energy metabolism and consequently reducing angiogenic capacity in endothelial cells. This impairment significantly influences diabetic wound healing. Our findings highlight the profound impact of transient hyperglycemia on wound healing, establishing METTL3 as a significant role in vascular complications of diabetes. This study not only elucidates the pathophysiological mechanisms behind MM in diabetic wounds but also suggests Nr-CWS as a potential therapeutic agent, offering a novel approach for treating diabetic wounds.

The increasing prevalence of diabetes in the United States continues to drive a steady rise in health care resource utilization, especially emergency department visits and all-cause hospitalizations, and the associated costs.

To investigate the impact of continuous glucose monitoring (CGM) on emergency department visits and all-cause hospitalizations among Medicaid beneficiaries with type 2 diabetes (T2D) treated with multiple daily insulin injections (MDIs) or basal insulin therapy (BIT) in a real-world setting.

In this retrospective, 12-month analysis, we used the Inovalon Insights claims dataset to evaluate the effects of CGM acquisition on emergency department visits and all-cause hospitalizations in the Managed Medicaid population. The analysis included 44,941 beneficiaries with T2D who were treated with MDIs (n = 35,367) or BIT (n = 9,574). Primary outcomes were changes in the number of emergency department visits and all-cause hospitalizations following 6 months after acquisition of CGM (post-index period) compared with 6 month prior to CGM acquisition (pre-index period). The first claim for CGM was the index date. Inclusion criteria were as follows: aged younger than 65 years, diagnosis of T2D, claims for short- or rapid-acting insulin (MDI group) or basal insulin (not rapid-acting) (BIT group), acquisition of a CGM device between January 1, 2017, and September 30, 2022, and continuous enrollment in their health plan throughout the pre-index and post-index periods.

In the MDI group, all-cause inpatient hospitalization rates decreased from 3.25 to 2.29 events/patient-year (hazard ratio = 0.12; 95% CI = 0.11-0.13; P < 0.001) and emergency department visit rates decreased from 2.15 to 1.86 events/patient-year (hazard ratio = 0.52; 95% CI = 0.50-0.53; P < 0.001). In the BIT group, all-cause inpatient hospitalization rates decreased from 1.63 to 1.39 events/patient-year (hazard ratio = 0.11; 95% CI = 0.09-0.12; P < 0.001) and emergency department visit rates decreased from 1.60 to 1.43 events/patient-year (hazard ratio = 0.47; 95% CI = 0.44-0.50; P < 0.001).

Acquisition of CGM is associated with significant reductions in emergency department visits and all-cause hospitalizations among people with T2D treated with MDIs or BIT.

The pathophysiological mechanisms of cardiovascular disease and microvascular complications in diabetes have been extensively studied, but effective methods of prevention and treatment are still lacking. In recent years, DNA methylation, histone modifications, and non-coding RNAs have arisen as possible mechanisms involved in the development, maintenance, and progression of micro- and macro-vascular complications of diabetes. Epigenetic changes have the characteristic of being heritable or deletable. For this reason, they are now being studied as a therapeutic target for the treatment of diabetes and the prevention or for slowing down its complications, aiming to alleviate the personal and social burden of the disease.This review addresses current knowledge of the pathophysiological links between diabetes and cardiovascular complications, focusing on the role of epigenetic modifications, including DNA methylation and histone modifications. In addition, although the treatment of complications of diabetes with "epidrugs" is still far from being a reality and faces several challenges, we present the most promising molecules and approaches in this field.

Autologous arteriovenous fistula (AVF) is preferred in hemodialysis patients. Maintaining its patency is a critical problem. This study aimed to create a nomogram model for predicting 1-year primary patency of AVF. Consequently, a total of 414 patients were retrospectively enrolled and randomly allocated to training and validation cohorts. Risk factors were identified by multivariable logistic regression and used to create a nomogram model. Performance of the model was evaluated by receiver operating characteristic (ROC) curve, Hosmer-Lemeshow test, and calibration curve. The results suggested that diameter of cephalic vein, low-density lipoprotein, glycosylated hemoglobin (%), and C-reactive protein were risk factors which could predict the patency of AVF. Area under ROC curves for training and validation cohorts were 0.771 and 0.794, respectively. Calibration ability was satisfactory in both cohorts. Therefore, present nomogram model could predict the 1-year primary patency of AVF.