Insulin Treatment Research Articles

Using Time in Tight Glucose Range as a Health-Promoting Strategy in Preschoolers With Type 1 Diabetes.

Children who develop diabetes in their first years of life risk being exposed to many decades of hyperglycemia, hence having a high risk of early complications and premature death. An additional age-dependent risk is that dysglycemia, especially hyperglycemia, negatively affects the developing brain. In evaluating the outcome of insulin treatment at an individual and group level, cutoff thresholds for glucose values are needed. Time in tight range (TITR) was defined as a measurement of time spent in a state of normoglycemia. The International Society of Pediatric and Adolescent Diabetes recommended that for preschoolers with type 1 diabetes (T1D), either >70% of time with glucose in range 70-180 mg/dL (3.9-10 mmol/L) or >50% of time in a tighter range 70-140 mg/dL (TITR) can be used as continuous glucose monitoring targets. In Sweden, over the past two decades, pediatric diabetes teams set glycemic targets to 70-140 mg/dL (3.9-7.8 mmol/L). Swedish registry data show that >50% of children <7 years old have >50% TITR. The purpose of this review is to share and discuss international knowledge and experiences of working with TITR as a health-promoting strategy in preschoolers with T1D on a structural and individual level. We conclude that as insulin treatment improves, a reasonable goal is to strive for as much time in a state of normoglycemia as possible, and this can easily be explained to families of children with diabetes. For children with access to an experienced health care team and diabetes technologies a currently realistic target can be at least half of the time in normoglycemic range, i.e., TITR >50%.

Insulin mitigates acute ischemia induced atrial fibrillation and sinoatrial node dysfunction ex vivo.

Acute atrial ischemia is a well-known cause of postoperative atrial fibrillation (POAF). However, mechanisms through which ischemia contributes to the development of POAF are not well understood. In this study, ex vivo Langendorff perfusion was used to induce acute ischemia and reperfusion in the heart in order to mimic POAF. Inducibility of atrial fibrillation (AF) was evaluated using programmed electrical stimulation and confirmed with open-atrium optical mapping. Compared to the control group without ischemia, 25 minutes of ischemia substantially increased the incidence of AF. The right atrium was more susceptible to AF than the left atrium. Administering insulin for 30 minutes before ischemia and during reperfusion with 25 minutes of ischemia greatly reduced the vulnerability to AF. However, insulin treatment during reperfusion only did not show substantial benefits against AF. Optical mapping studies showed that insulin mitigates ischemia-induced abnormal electrophysiology, including shortened action potential duration and effective refractory period, slowed conduction velocity, increased conduction heterogeneity, and altered calcium transients. In conclusion, insulin reduced the risk of acute ischemia/reperfusion-induced AF via improving the electrophysiology and calcium handling of atrial cardiomyocytes, which provides a potential therapy for POAF.

Acute hyperglycemia exacerbates neuroinflammation and cognitive impairment in sepsis-associated encephalopathy by mediating the ChREBP/HIF-1α pathway.

Delirium is a prominent symptom of sepsis-associated encephalopathy (SAE) and is highly prevalent in septic patients hospitalized in the intensive care unit, being closely connected with raised mortality rates. Acute hyperglycemia (AH) has been recognized as a separate risk factor for delirium and a worse prognosis in critically sick patients. Nevertheless, the exact contribution of AH to the advancement of SAE is still unknown. This research retrospectively evaluated the connection between blood glucose levels (BGLs) and the incidence of delirium and death rates in septic patients in the ICU of a tertiary comprehensive hospital. In addition, a septic rat model was induced through cecal ligation and puncture (CLP), after which continuous glucose infusion was promptly initiated via a central venous catheter post-surgery to evaluate the potential implications of AH on SAE. Next, septic rats were assigned to four groups based on target BGLs: high glucose group (HG, ≥ 300mg/dL), moderate glucose group (MG, 200-300mg/dL), normal glucose group (NG, < 200mg/dL), and a high glucose insulin-treated group (HI, 200-300mg/dL) receiving recombinant human insulin treatment (0.1IU/kg/min). The sham group (SG) received an equivalent volume of saline infusion and denoted the NG group. The effects of AH on neuroinflammation and cognitive function in septic rats were evaluated using behavioral tests, histopathological examination, TUNEL staining, ELISA, and Western blot. The effects of glucose levels on microglial activation and glucose metabolism following lipopolysaccharide (LPS, 1μg/mL) exposure were assessed using CCK8 assay, qRT-PCR, Western blot, and ELISA. Our findings revealed that AH during sepsis was a separate risk factor for delirium and assisted in predicting delirium occurrence. AH raised the levels of systemic and central inflammatory cytokines in septic rats, promoting neuronal apoptosis, blood-brain barrier disruption, and cognitive impairment. In addition, both in vivo and in vitro, an elevated glucose challenge increased the ChREBP, HIF-1α, glycolytic enzymes, and inflammatory cytokines expressions in microglia after exposure to CLP or LPS. These results collectively suggest that hyperglycemia can exacerbate neuroinflammation and delirium by enhancing microglial glycolysis under septic conditions, potentially mediated by upregulation of the ChREBP/HIF-1α signaling pathway.

The effect of diabetes education on maternal and neonatal outcomes in pregnant women diagnosed with gestational diabetes.

Education during pregnancy is important for the development of the pregnant woman's ability to adapt to change and for a healthy birth. In this study, we aimed to examine the effects of education through a diabetes education program on maternal and newborn health in women diagnosed with gestational diabetes. In our study, we compared the maternal and neonatal health outcomes of pregnant women who participated in the diabetes education program and were diagnosed with gestational diabetes with the outcomes of pregnant women who did not participate in the diabetes education program and were diagnosed with gestational diabetes. The study included patients who were diagnosed with diabetes between 24and 26 weeks gestation at a tertiary education and research hospital and who underwent a 75-gram OGTT test. Age, BMI, parity, method of delivery, weight gain during pregnancy, newborn birth weight, gestational age and Apgar scores were compared. The study included 119 patients and analyzed maternal-neonatal outcomes. There were no statistically significant differences in age (33 ± 5.7 versus 31 ± 5.2), body mass index (BMI) (32.2 vs. 31.2), gravidity, parity, number of miscarriages, mode of delivery, family history of diabetes, smoking, prenatal corticosteroid use, and gestational age at delivery. The HbA1c value (p: 0.013), the total weight gain during pregnancy (p: 0.015), the need for insulin treatment (p: 0.002), and the birth weight (0.005) were significantly higher in the group without diabetes education. In our study, diabetic school education was associated with lower HbA1c levels, less weight gain and less need for insulin therapy. When the results were categorized by insulin use, it was found that in patients using insulin, those who received diabetic school education had fewer macrosomic fetuses, whereas in patients not using insulin, those who received diabetic school education had lower maternal weight gain during pregnancy.

Practice guideline: Statement regarding treatment for suspected slowly progressive type 1 diabetes (SPIDDM; probable) cases (English version).

Insulin treatment should be introduced in patients with slowly progressive type 1 diabetes (SPIDDM; definite), according to the revised diagnostic criteria of SPIDDM (2023). In contrast, SPIDDM (probable) patients are in a non-insulin-dependent state; therefore, a more flexible treatment can be considered, although sulfonylurea agents should be avoided. Insulin treatment has been shown to maintain endogenous insulin secretion capacity in SPIDDM (probable); however, this does not mean that all SPIDDM (probable) patients should use insulin from the early phase. Dipeptidyl peptidase-4 inhibitors and biguanides might be the treatment of choice for SPIDDM (probable), but no evidence exists for other hypoglycemic agents. In any case, careful monitoring of the endogenous insulin secretion capacity should be carried out, and if a decrease in insulin secretion capacity is suspected, a change in treatment should be considered to prevent progression to an insulin-dependent state.

Type 2 diabetes pathway-specific polygenic risk scores elucidate heterogeneity in clinical presentation, disease progression and diabetic complications in 18,217 Chinese individuals with type 2 diabetes.

Type 2 diabetes is a complex and heterogeneous disease and the aetiological components underlying the heterogeneity remain unclear in the Chinese and East Asian population. Therefore, we aimed to investigate whether specific pathophysiological pathways drive the clinical heterogeneity in type 2 diabetes. We employed newly developed type 2 diabetes hard-clustering and soft-clustering pathway-specific polygenic risk scores (psPRSs) to characterise individual genetic susceptibility to pathophysiological pathways implicated in type 2 diabetes in 18,217 Chinese patients from Hong Kong. The 'total' type 2 diabetes polygenic risk score (PRS) was summed by genome-wide significant type 2 diabetes signals (n=1289). We examined the associations between psPRSs and cardiometabolic profile, age of onset, two glycaemic deterioration outcomes (clinical requirement of insulin treatment, defined by two consecutive HbA1c values ≥69 mmol/mol [8.5%] more than 3 months apart during treatment with two or more oral glucose-lowering drugs, and insulin initiation), three renal (albuminuria, end-stage renal disease and chronic kidney disease) outcomes and five cardiovascular outcomes. Although most psPRSs and total type 2 diabetes PRS were associated with an earlier and younger onset of type 2 diabetes, the psPRSs showed distinct associations with clinical outcomes. In particular, individuals with normal weight showed higher psPRSs for beta cell dysfunction and lipodystrophy than those who were overweight. The psPRSs for obesity were associated with faster progression to clinical requirement of insulin treatment (adjusted HR [95% CI] 1.09 [1.05, 1.13], p<0.0001), end-stage renal disease (1.10 [1.04, 1.16], p=0.0007) and CVD (1.10 [1.05, 1.16], p<0.0001) while the psPRSs for beta cell dysfunction were associated with reduced incident end-stage renal disease (0.90 [0.85, 0.95], p=0.0001) and heart failure (0.83 [0.73, 0.93], p=0.0011). Major findings remained significant after adjusting for a set of clinical variables. Beta cell dysfunction and lipodystrophy could be the driving pathological pathways in type 2 diabetes in individuals with normal weight. Genetic risks of beta cell dysfunction and obesity represent two major genetic drivers of type 2 diabetes heterogeneity in disease progression and diabetic complications, which are shared across ancestry groups. Type 2 diabetes psPRSs may help inform patient stratification according to aetiology and guide precision diabetes care.

Interleukin 37 Role in Diabetic Iraqi Patients: A comparison between patients treated with and without Insulin

Background: Diabetes Mellitus (DM) is defined as a metabolic disorder that is characterized by some clinical features, such as chronic hyperglycemia accompanied by impairment of carbohydrates metabolism, proteins, and lipids. However, relative or absolute insulin deficiency is associated with the high blood glucose levels, which is attributed to the β-cells dysfunction, insulin resistance or could be both. The anti-inflammatory cytokine interleukin-37 (IL-37) negatively regulates inflammation, therefore, reduces inflammation and alters metabolic pathways. It acts by suppressing inflammatory cytokines and chemokines, activation of IL-37 inhibits inflammation and obstructs the infiltration of pro-inflammatory cells, primarily neutrophils and eosinophils. Aim of Study: The estimation of IL 37 and other biochemical parameters in patients with Diabetes mellitus and study its role in the pathogenicity of the disease. Materials and methods: A case-control study design was adopted to study the relationship between Interleukin 37 and insulin treatment in Nasiriyah in the Diabetes and Endocrinology Specialized Center between December 2023 and January 2024. It was conducted on patients with Diabetes Mellitus type 2 (60 patients) divided into two groups (30 patients treated with Insulin injection) and (30 patient treated with oral tab only). On the other hand, 30 people were taken as a control group without Diabetes Mellitus.Result: Patients with diabetes mellitus have been noticed to have higher levels of IL-37 in comparison to the healthy control groups. In general, patients with diabetes mellitus have higher levels of IL-37 compared to three groups, G1, G2, and healthy control groups. Conclusion We demonstrated that serum levels concentration of IL 1b and IL 37 significantly increased in our patients also FBS, HbA1c, Insulin Resistance, HOMO IR, TG, cholesterol, and decrease C- peptide as compared to healthy individuals.

Breast cancer in women with previous gestational diabetes: a nationwide register-based cohort study

BackgroundGestational diabetes mellitus (GDM) is a common pregnancy complication characterized by insulin resistance. A link has been suggested between insulin resistance and breast cancer, which is the most common cancer in women. Hence, women with previous GDM may be at increased risk of developing breast cancer, yet, the existing evidence is conflicting. This study explored the association between GDM and incident breast cancer, including age at cancer diagnosis. Additionally, we investigated the potential impact of severity of insulin resistance during pregnancy and of subsequent diabetes development on the breast cancer risk.MethodsWe conducted a nationwide, register-based cohort study including all women giving birth in Denmark from 1997 to 2018. We defined GDM and breast cancer based on ICD-10 codes. Premenopausal and postmenopausal breast cancer was pragmatically defined as age at outcome < 50 years and ≥ 50 years, respectively. A proxy for severity of insulin resistance during pregnancy was based on insulin treatment; subsequent diabetes was defined as presence of ICD-10 codes and/or antidiabetic medication after pregnancy. The statistical analyses included Cox regression, logistic regression and t-test.ResultsOf 708,121 women, 3.4% had GDM. The median follow-up period was 11.9 years (range 0-21.9). The overall breast cancer risk was comparable in women with and without previous GDM (adjusted hazard ratio 0.96 [95% CI 0.83–1.12]). Premenopausal and postmenopausal breast cancer risk also did not differ; however, women with previous GDM had a breast cancer diagnosis at younger age (42.6 vs. 43.5 years, p-value 0.01). All-cause mortality was similar regardless of GDM history. Severity of insulin resistance during pregnancy and subsequent diabetes did not affect breast cancer risk.ConclusionsThis large, population-based cohort study showed no higher risk of incident breast cancer in women with previous GDM compared to women without previous GDM after a median of almost 12 years of follow-up. This was evident irrespective of menopausal state. The breast cancer risk was not influenced by the severity of insulin resistance during pregnancy and by subsequent diabetes development. Regardless of GDM history, attention towards prevention, early detection and treatment of breast cancer should be prioritized.

Influence of Diabetes Mellitus on Neurological Recovery in Older Patients With Cervical Spinal Cord Injury Without Bone Injury: A Retrospective Multicenter Study.

Retrospective study. To investigate the impact of diabetes mellitus on neurological recovery and determine the relationship between moderate-severe diabetes and neurological recovery in patients with cervical spinal cord injury (CSCI) without bone injury. A retrospective study was conducted on 389 consecutive patients aged ≥65 years with CSCI without bone injury across 33 medical institutes. The patients were divided into a nondiabetic group (n = 270) and a diabetic group (n = 119). Neurological outcomes were compared between the two groups through propensity score matching. The impact of moderate-severe diabetes (defined as hemoglobin A1c ≥ 7.0% or requiring insulin treatment) on neurological recovery was evaluated through multiple linear regression analysis. Propensity score matching revealed no significant differences between the diabetic and nondiabetic groups in terms of American Spinal Injury Association (ASIA) impairment scale grade and mean total ASIA motor scores (AMS) at 6 months post-injury. Multiple linear regression analysis indicated that age on admission (B = -0.34; 95% confidence interval [CI], -0.59 to -0.08; P = 0.01), dementia (B = -16.50; 95% CI, -24.99 to -8.01; P < 0.01), and baseline total AMS (B = -0.62; 95% CI, -0.72 to -0.51; P < 0.01) were negative predictors of neurological recovery at 6 months post-injury. The presence of moderate-severe diabetes did not influence neurological recovery at 6 months post-injury. Diabetic patients with CSCI without bone injury achieved improvements in neurological function comparable to those of nondiabetic patients. Moderate-severe diabetes did not affect neurological recovery in patients with CSCI without bone injury.

Comparison of clinical characteristics, microvascular complications and inflammatory markers in type 2 diabetic patients under insulin versus metformin treatment: A cross-sectional study at Karbala Diabetic Center, Iraq.

Type 2 diabetes mellitus (T2DM) is a major global health issue associated with chronic inflammation, which contributes to both disease progression and its complications, including cardiovascular and microvascular disorders. Key inflammatory markers such as tumor necrosis factor-alpha, interleukin-6 (IL-6), E-selectin, and P-selectin are elevated in T2DM patients and are implicated in the development of these complications. Understanding how treatments such as insulin and metformin affect these markers is crucial for improving therapeutic strategies in T2DM. This study investigated the effects of insulin and metformin on these inflammatory markers in T2DM patients. This was a cross-sectional study involving patients with diabetes on insulin (group A), metformin only (group B), and healthy controls (group C). Participants were enrolled from the Diabetic Center in Karbala, Iraq and underwent clinical assessments including ophthalmologic examinations. Fasting blood glucose, HbA1c and lipids levels were assessed. The levels of inflammatory markers (IL-6 and TNF-α), and adhesion molecules (sE-selectin and sP-selectin) were measured using Enzyme-Linked Immunosorbent Assay (ELISA). The study included 522 patients with diabetes: 356 receiving insulin (group A), 70 receiving metformin (group B) and 96 healthy controls (group C). T2DM patients treated with insulin exhibited significantly more microvascular complications than those treated with metformin. Higher rates of retinopathy (64.3% vs 11.4%) and neuropathy (69.9% vs 11.4%) were observed in the insulin group, whereas the incidence of nephropathy did not differ significantly (14.6% vs 11.4%). Inflammatory markers were lower in the insulin group: TNF-α levels were 3-fold lower and IL-6 levels were 8-fold lower. Conversely, sE-selectin levels were 1.5-fold higher in the insulin group, and sP-selectin levels were 1.4-fold higher in the metformin group. This study highlights distinct differences in inflammatory markers and systemic complications between T2DM patients treated with insulin and those treated with metformin alone. Further research is needed to explore the mechanisms underlying these observations and optimize treatment strategies for T2DM patients.

Automated insulin delivery systems in elderly patients with brittle type 2 diabetes

PurposeGeriatric diabetes is complicated by the frailty of this population, and hypoglycemia with insulin is not uncommon in these patients. Automated Insulin Delivery (AID) systems may provide better glycemic control in elderly patients with brittle type 2 diabetes. MethodsThirty-four patients (≥ 60 years) including cancer patients with brittle diabetes were switched to an AID system from multiple-dose insulin (MDI) treatment. HbA1c level, weight, total daily insulin requirement, and C-peptide, creatinine, and lipids were followed for at least six months. ResultsThere were 34 patients (14 male, 41.2 %) with a median age of 67 (IQR 63.0–75.5). Six patients (17.6 %) were on chemotherapy and/or steroids (Ch/S). The patients’ initial median HbA1c % was 9.3 (IQR 7.6–11.0), c-peptide level was 0.9 (IQR 0.5–2.2) ng/mL, and median total daily insulin dose was 41 IU (IQR 32–53).Six months after the patients were switched to an AID system their HbA1c % decreased to 7.1 (IQR 6.5–8.1), p < 0.001 and c-peptide increased to 1.21 (IQR 0.2–1.7) ng/mL, p = 0.878. Total insulin dose decreased with AID systems [32 IU (IQR 23.9–37.8)), p < 0.001].There was a decrease in median HbA1c % in patients on Ch/S [8.7 (IQR 7.0–11.5) to 6.9 (IQR 6.3–9.2)] however it didn’t reach statistical significance p = 0.225. Total insulin dose also decreased without statistical significance [33 IU (IQR 41–28) to 28 (IQR 23–35), p = 0.173].The mean time in range (TIR) percent of the patients with AID systems were as follows; <54 mg/dL was 0.5 %, 56–70 mg/dL was 1.3 %, 70–180 mg/dL was 64.8 %, >180 mg/dL was 26.7 % and > 250 mg/dL was 6.7 %. ConclusionAlthough AID systems are tested mostly in young type 1 patients our results show that elderly patients with brittle type 2 diabetes also benefit from an AID system. Even in very frail patients such as cancer patients, improvement can be seen.

Economic Evaluation of Once-Weekly Insulin Icodec from Italian NHS Perspective.

Icodec, once-weekly basal insulin, aims to simplify therapy management by reducing injection frequency for diabetic patients. The efficacy and safety of icodec were evaluated in the ONWARDS clinical development program. This study evaluates icodec economic and quality of life impact from the Italian National Healthcare System (NHS) perspective. A pharmacoeconomic study was developed to assess the once-weekly insulin icodec value, highlighting its potential to decrease needle use while improving adherence and quality of life. In the base case, a differential cost and cost-utility analysis over one year compared to once-daily insulin degludec were developed. Based on the comparison with degludec, a scenario analysis was planned between icodec and the mix of basal insulins available on the market. Economic evaluations included drug and administration costs, needles, and impact on adherence. The cost-utility analysis measured the utility associated with the weekly injection compared to the daily ones, resulting in an incremental cost-effectiveness ratio (ICER), measured as Δ€/ΔQALY (Quality Adjusted Life Years). To assess the robustness of the results, a deterministic one-way sensitivity analysis and a probabilistic sensitivity analysis were carried out. At an annual cost 25% higher than degludec, considering the economic benefits generated by the needle use reduction (-€51.10) and adherence improvement (-€54.85), once-weekly icodec grants no incremental cost and even potential savings per patient. Furthermore, icodec reported a utility advantage (0.023). It achieved a dominant incremental cost-effectiveness ratio (ICER) compared to degludec. The comparison with the mix of basal insulins also reported a cost-effectiveness profile. Sensitivity tests conducted confirmed the robustness of the findings, highlighting the key drivers of the analysis. Icodec represents a new therapeutic option to simplify basal insulin treatment. It also improves the patient's management and his quality of life, without increasing the economic burden for the Italian NHS, while guaranteeing an excellent cost-effectiveness profile.

IMPLEMENTATION AND OUTCOME OF A PROTOCOL-BASED TREATMENT FOR DIABETIC KETOACIDOSIS IN A TERTIARY CARE PEDIATRIC EMERGENCY DEPARTMENT

BackgroundThe standardization of clinical practice in emergency treatment of diabetic ketoacidosis (DKA) is a prerequisite for improving patient care. For this purpose, a standardized DKA protocol incorporating a two-bag system has been implemented since January 2020 in our center. ObjectivesTo assess the impact of the development and utilization of the standard treatment pathway for DKA on patient outcomes. MethodsThis retrospective cohort study involved patients diagnosed with DKA and admitted to the pediatric emergency department (PED). The entire period of the study was from January 2017 to September 2022. Patients with DKA managed before and after implementation of the protocol were compared in terms of clinical outcomes. ResultsOut of 145 patients, 77 (53%) patients were in the pre-protocol group, 68 (47%) were in the protocol group. Age, sex, and severity of DKA were similar between the groups. Implementation of the protocol resulted in shorter resolution time of acidosis and ketosis (p = 0.007, p < 0.001, respectively), higher correction rates of bicarbonate and blood ketones (p = 0.003, p < 0.001, respectively), shorter duration of IV insulin treatment (p = 0.008), more appropriate potassium dosage administrating to IV fluids (p < 0.001), lower incidence of hypokalemia, hypophosphatemia, and hypoglycemia (p = 0.008, p = 0.002, p = 0.036, respectively), and smaller number of IV bags use (p < 0.001). ConclusionImplementation of a protocol-based pathway for DKA involving a two-bag system provided earlier correction of ketoacidosis, decreased the risk of complications, and reduced resource utilization in the PED.

Transcription factor ETV4 plays a critical role in the development of non-alcoholic fatty liver disease

The Angiopoietin-like 4 (ANGPTL4) and ETS Variant Transcription Factor 4 (ETV4) are involved in the metabolic transition and carcinogenesis in the liver. However, the role of ETV4 in the development of non-alcoholic fatty liver disease (NAFLD) is currently unknown. Our study reveals that ETV4 expression was upregulated in the diet-induced non-alcoholic fatty liver disease, and plays a critical role in the dysregulated lipid metabolism. We demonstrate a mechanism by which ANGPTL4 regulates lipid homeostasis via involving the AMPK/ETV4 axis. Transient knockdown of ETV4 abolished the ANGPTL4-induced expression of Srebp1c, Acc and Fasn. Insulin treatment potentially increased the physical association of ETV4 with SREBP1, and promotes nuclear translocation and transcriptional activity of SREBP1. In addition, we show that combined therapy with omega-3 fatty acids and diacylglycerol O-acyltransferase inhibitor 1 (DGAT1) inhibitor (A-922500) counteracted the ANGPTL4-ETV4 axis-induced lipogenesis in vitro, and in vivo in obese mice via activation of GPR120-βarrestin2-AMPK pathway. Finally, we demonstrate that targeted pharmacologic therapy using GalNac-ETV4 siRNA that specifically inhibits ETV4 gene expression in the liver protects against diet-induced NAFLD, obesity and dyslipidemia. Hence, our study reveal previously unrecognized role of ETV4 in the NAFLD, and provides rationale targeting ETV4 to treat NAFLD.

Post-COVID syndrome and type 2 diabetes mellitus in Kazakhstan: clinical manifestations and vaccine efficacy.

In this article, we report the results of a survey investigating post-coronavirus disease 2019 (COVID-19) syndrome in patients with type 2 diabetes mellitus and the impacts of vaccination on long-term manifestations. From February 2022 to April 2023, a survey of patients with type 2 diabetes and people without diabetes who were treated for a coronavirus infection was conducted in Kazakhstan. Participants were invited via social media to voluntarily participate in this study. A total of 417 surveys were included in this study, comprising 212 patients with type 2 diabetes and 205 without diabetes. We compared persistent complaints after recovery in patients with and without diabetes mellitus (DM), as well as vaccination status. The results of this study on self-reported symptoms of prolonged COVID show that more than half of those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Kazakhstan have at least one persistent symptom after recovery. Based on the list of prolonged COVID-19 symptoms reported by patients with type 2 DM (T2DM), exertional dyspnoea, fatigue, respiratory discomfort, headaches, and sleep disturbances are among the most common ongoing conditions, and in many cases last more than 3 months after COVID-19. Patients with T2DM experience more severe and prolonged symptoms than those without diabetes. Additionally, vaccination lowers COVID-19 hospitalization risk and decreases the need for adjusting hypoglycemic therapy, such as insulin treatment, after recovering from SARS-CoV-2 infection.

Gestational diabetes and pregnancy outcome in Kurdish, Somali and general population in Finland

Abstract Gestational diabetes (GDM) increases the risk of type II diabetes and cardiovascular morbidity later in life but GDM incidence in women from different cultural backgrounds varies. This study aims to examine treatment of GDM and pregnancy outcomes in Somali, Kurdish and general population women. Patient data of 312 Kurdish, 254 Somali and 508 general population women was collected from Turku University Hospital records from 2008 to 2019. The general population was selected by randomization with matching year, BMI, age, and parity. Singleton deliveries after 34th gestational week with no prior diabetes mellitus were included. Descriptive and comparison analyses (SPSS, version 29.0) were used to identify associations between ethnic background and pregnancy outcomes in women with GDM. The incidence of GDM was 22 % (CI 95 % 17-27) in Somali, 36 % (CI 95 % 31-42) in Kurdish, and 16 % (CI 95 % 13-19) in the general population women. Kurdish women had medication for GDM more often (43 % CI 95 % 34-53) than the Somali (22 % CI 95 % 11-33) and general population women (18 % CI 95 % 9-26). Metformin was more commonly used among Kurdish (30 % CI 95 % 22-39) compared to the general population (12 % CI 95 % 4-18) and Somali women (13 % CI 95 % 4-22). There was no difference in insulin or combined metformin and insulin treatment between the groups. In GDM group, vaginal deliveries were more common in general population (89 % CI % 81-95) than in Somali women (67 % CI % 64-81). Induction of labour (indication GDM or other) and instrumental vaginal delivery rates were similar between the groups. Newborns of all Somali women had a lower weight (SD -0.3 CI 95 % -0.7 - -0.2) compared to the general population (SD 0 CI 95 % -0.1 - 0.3). The prevalence of GDM was increased and dietary treatment decreased in Kurdish women compared to the general population in Finland. In the future, the treatment of GDM should be adjusted to better optimize the care for different cultural background women. Key messages • Kurdish women have increased incidence of GDM and less dietary treatment compared to the general population with similar risk factors. The pregnancy outcomes remain good in all groups. • With Somali women, the birth weight of the child is lower despite GDM status. This might direct clinicians to underestimate the effect of GDM when considering individual treatment.

Insulin Stabilization Designs for Enhanced Therapeutic Efficacy and Accessibility.

ConspectusInsulin has remained indispensable in the treatment of diabetes since it was first discovered in 1921. Unlike small molecular drugs, insulin and other protein drugs are prone to degradation when exposed to elevated temperatures, mechanical agitation during transportation, and prolonged storage periods. Therefore, strict cold-chain management is crucial for the insulin supply, requiring significant resources, which can limit the access to insulin, particularly in low-income areas. Moreover, although insulin formulations have advanced tremendously in the last century, insulin treatment still imposes a challenging regimen and provides suboptimal outcomes for the majority of patients. There is an increasing focus on pursuing improved pharmacology, specifically on safer, more user-friendly insulin therapies that minimize the self-management burden. These challenges underscore the need for developing novel insulin formulations with improved stability that are compatible with advanced insulin therapy.Insulin stabilization can be achieved through either chemical modification of insulin or formulation component design. Inspired by insulin-like peptides from invertebrates, we have developed novel stable insulin analogs based on a fundamental understanding of the insulin receptor engagement for insulin bioactivity. We created a novel four-disulfide insulin analog with high aggregation stability and potency by introducing a fourth disulfide bond between a C-terminal extended insulin A-chain and residues near the C-terminus of the B-chain. In an effort to stabilize insulin in its monomeric state to develop ultrafast-acting insulin with rapid absorption upon injection, we have developed a series of structurally miniaturized yet fully active insulin analogs that do not form dimers due to the lack of the canonical B-chain C-terminal octapeptide. Additionally, our study provided strategies for expanding the scope of cucurbit[7]uril (CB[7])-assisted insulin stabilization by engineering safe and biodegradable CB[7]-zwitterionic polypeptide excipients. We also explored insulin N-terminal substitution methods to achieve pH-dependent insulin stabilization without prolonging the duration of action.This Account describes our exploration of engineering stable insulin analogs and formulation design strategies for stabilizing insulin in aqueous solutions. Beyond conventional stabilization strategies for insulin injections, the unmet challenges and recent innovations in insulin stabilization are discussed, addressing the growing demand for alternative, less invasive routes of insulin administration. Additionally, we aim to provide a thorough overview of insulin stabilization from the perspective of commercially available insulin drugs and common pharmaceutical engineering practices in the industry. We also highlight unresolved insulin stabilization challenges and ongoing research strategies. We anticipate that further emphasis on collective efforts of protein engineering, pharmaceutical formulation design, and drug delivery will inform the development of stable and advanced insulin therapy.

Diabetes mellitus and adverse clinical events in patients with atrial fibrillation: implications of insulin treatment: a report from the GLORIA-AF Registry Phase III

Abstract Background Atrial Fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations has not been fully elucidated, especially in relation to insulin use. Purpose To analyze the associations between DM and the risk of clinical adverse events in patients with AF, and second, explore the impact of insulin treatment in these patients. Methods We studied patients with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-years follow-up. Clinical events included all-cause death, major bleeding, myocardial infarction (MI), stroke, thromboembolism (TE), and major adverse cardiovascular events (MACE). MACE was defined as a composite of stroke, MI and major bleeding. Kaplan-Meier curves were used to estimate the cumulative incidence of clinical events. Multivariable cox regression models with subgroups were used to estimate the association between DM and the risk of mortality and clinical events. Results A total of 15,861 AF patients were included (mean age 70.00 ± 10,21 years old; 55% male, 20% Asia), of which 3,666 had DM (mean age 70.04 ± 9.54 years old; 59% male, 21% Asia). Kaplan-Meier curves showed that AF patients with DM had higher cumulative hazard of all outcomes, including all-cause death (OR: 1.56, 95%CI: 1.38-1.77), CVD (OR: 1.72, 95%CI: 1.44-2.06), major bleeding (OR: 1.4, 95%CI: 1.17-1.67), stroke (OR: 1.29, 95%CI: 1.04-1.61), TE (OR: 1.26, 95%CI:1.02-1.56), MI (OR: 1.88, 95%CI: 1.48-2.39) and MACE (OR: 1.61, 95%CI: 1.41-1.84). After adjustment by prior disease and drugs, the outcomes of stroke (OR: 1.19, 95%CI: 0.95-1.49) and TE (OR: 1.22, 95%CI: 0.98-1.52) showed not significant. Subgroup analysis found that increased risks of stroke were found in female (OR: 1.43, 95%CI: 1.03-1.98, Pinteraction = 0.062) and non-Asian patients (OR: 1.39, 95%CI: 1.06-1.82, Pinteraction = 0.175) with DM. For all cause death, subgroup results were similar with overall patients. In addition, insulin use increased the risk of all cause death (OR: 1.82, 95%CI: 1.45-2.29), CVD (OR: 1.70, 95%CI: 1.22-2.37), major bleeding (OR: 1.54, 95%CI: 1.08-2.18), MI (OR: 1.72, 95%CI: 1.12-2.64), MACE (OR: 1.65, 95%CI: 1.28-2.11) in patients with AF and DM. Multivariable model showed similar result. Conclusions DM was independently associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF. Insulin use was associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF and DM.Figure 1Figure 2

Twelve-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with type 1 diabetes mellitus

Abstract Background Individuals diagnosed with type 1 diabetes mellitus (T1DM) exhibit indications of vascular and endothelial dysfunction earlier in comparison to healthy individuals. Evidence shows that SGLT-2 inhibitors (SGLT-2i) have a beneficial impact on cardiovascular health in individuals with type 2 diabetes mellitus (T2DM). We investigated the effects of dapagliflozin on endothelial and cardiovascular function in patients with T1DM. Methods We recruited in total 40 patients with T1DM and pour glycemic control who were treated with insulin and received dapagliflozin (n=20) or intensification of insulin treatment (n=20) (control group). We measured at baseline and at twelve months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical) b) Central systolic blood pressure (cSBP) c) Perfused boundary region (PBR) of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness) and d) Left ventricular global longitudinal strain (GLS) using speckle-tracking echocardiography. Results At baseline, patients among the two groups had similar age, sex, HbA1c and markers of endothelial and cardiovascular function (p&amp;gt;0.05). After 12 months of treatment, patients who received dapagliflozin displayed an improvement in PBR5–25 (−16%, p&amp;lt;0.05), in PWV (−9.3%, p&amp;lt;0.05), in cSBP (−6%, p&amp;lt;0.05) and in GLS (+4%, P&amp;lt;0.05) compared to baseline. However, no statistically significant changes in PBR5–25, in PWV, in cSBP and in GLS were observed after intensification of insulin treatment (PBR5–25: +0.4%, PWV: -1%, cSBP: −2%, GLS: −1% at 4 months, P&amp;gt;0.05), despite a similar HbA1c reduction (Table 1). Changes of PBR after one year treatment with dapagliflozin correlated with a concomitant reduction of PWV and cSBP (P&amp;lt;0.05). Conclusions Twelve months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with T1DM, independently of glycemic control.

Tests employed in the psychometric validation of the Insulin Treatment Appraisal Scale (ITAS) in T2DM patients; a systematic review of the literature

BackgroundPsychological Insulin Resistance (PIR) and negative perceptions regarding insulin treatment are noteworthy challenges in T2DM management, which hinder the timely initiation of insulin treatment. To get past these obstacles a reliable tool is required to evaluate patients’ perspectives on insulin administration. Our study aims to conduct a comprehensive systematic review to evaluate the validity and reliability of different validation tests used in the psychometric validation of the ITAS in T2DM patients.MethodsA literature search was carried out, using PubMed, Google Scholar, EMBASE, Cochrane Library and Science Direct. Only those studies assessing content validity, construct validity, concurrent validity, discriminant validity, internal consistency reliability (Cronbach’ α), and items-total correlation were retrieved.ResultsA total of 14 studies illustrated the validity and reliability of ITAS in T2DM patients. Content validity results of S-CVI was 0.97, and I-CVI was 0.8–1.00. Construct validity with factor loading was greater than the threshold value of 0.3. The concurrent validity of ITAS vs. PAID, WHO-5, and SPI was 0.35 (P < 0.05), −0.14 (P < 0.05), and 0.80 (P < 0.001) respectively. The mean difference between insulin and non-insulin group was significant (P < 0.001) showing reliable discriminant validity. Reported results of Cronbach’s α for the main scale (0.79–0.89), subscale-1 (0.72–0.9), and subscale-2 (0.61–0.89) showed “good to excellent” internal consistency reliability of ITAS. Item-total correlation results for the main scale, subscale-1, and subscale-2 were (0.40–0.82), (0.31–0.74) and (0.34–0.58) respectively. Test-retest reliability of ITAS was 0.571–0.87.ConclusionsStudy findings confirm the robustness of various validation tests utilized in the psychometric validation of ITAS in T2DM patients. ITAS is a well-validated and reliable tool for determining the perspectives, PIR, and changes in patients’ perception over time and it can be used to overcome hurdles in the timely initiation of insulin treatment in T2DM patients.