Insulin Treatment Research Articles

Patient-reported outcome measures for medication treatment satisfaction: a systematic review of measure development and measurement properties

BackgroundMedication Treatment Satisfaction (M-TS) from the patients’ perspective is important for comprehensively evaluating the effect of medicines. The extent to which current patient-reported outcome measures (PROMs) for M-TS are valid, reliable, responsive, and interpretable remains unclear. To assess the measurement properties of existing PROMs for M-TS and to highlight research gaps.MethodsUsing PubMed, Embase (Ovid), Cochrane library (Ovid), IPA (Ovid), PsycINFO, Patient-Reported Outcome and Quality of Life Questionnaires biomedical databases, and four Chinese databases, we performed a systematic search for studies addressing the development and validation of PROMs for M-TS. Based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, pairs of reviewers independently assessed the measurement properties of the PROMs and rated the quality of evidence on the measurement properties of each PROM. (The Open Science Framework registration: https://doi.org/10.17605/OSF.IO/8S5ZM).ResultsThis review identified 69 PROMs for M-TS in 114 studies (four generic, 32 disease-specific, and 33 drug-specific) of which 60 were intended for adults. All provided limited or no information regarding interpretability. Most demonstrated appropriate construct validity including convergent validity (39/69) and discriminative or known-groups validity (40/69) (high to moderate quality of evidence). Only a few provided evidence of sufficient content validity (8/69), structural validity (13/69), and internal consistency (11/69). Of 38 PROMs reporting test–retest reliability, results in 24 provided evidence of satisfactory test–retest reliability (18 with high to moderate, 6 with low to very low quality of evidence). Few PROMs reported responsiveness (16/69). Two generic PROMs (Treatment Satisfaction Questionnaire for Medication initial Version 1.4, TSQM-1.4; Treatment Satisfaction with Medicines Questionnaire, SATMED-Q) and one drug-specific PROM (Insulin Treatment Satisfaction Questionnaire, ITSQ) demonstrated both satisfactory validity and reliability.ConclusionsMost existing PROMs for M-TS require further exploration of measurement properties. Reporting guidelines are needed to enhance the reporting quality of the development and validation of PROMs for M-TS.

Identification and functional characterisation of DNA methylation differences between East- and West-originating Finns

ABSTRACT Eastern and Western Finns show a striking difference in coronary heart disease-related mortality; genetics is a known contributor for this discrepancy. Here, we discuss the potential role of DNA methylation in mediating the discrepancy in cardiometabolic disease-risk phenotypes between the sub-populations. We used data from the Young Finns Study (n = 969) to compare the genome-wide DNA methylation levels of East- and West-originating Finns. We identified 21 differentially methylated loci (FDR < 0.05; Δβ >2.5%) and 7 regions (smoothed FDR < 0.05; CpGs ≥ 5). Methylation at all loci and regions associates with genetic variants (p < 5 × 10−8). Independently of genetics, methylation at 11 loci and 4 regions associates with transcript expression, including genes encoding zinc finger proteins. Similarly, methylation at 5 loci and 4 regions associates with cardiometabolic disease-risk phenotypes including triglycerides, glucose, cholesterol, as well as insulin treatment. This analysis was also performed in LURIC (n = 2371), a German cardiovascular patient cohort, and results replicated for the association of methylation at cg26740318 and DMR_11p15 with diabetes-related phenotypes and methylation at DMR_22q13 with triglyceride levels. Our results indicate that DNA methylation differences between East and West Finns may have a functional role in mediating the cardiometabolic disease discrepancy between the sub-populations.

Educational Interventions for Individuals with Insulin-Treated Type 2 Diabetes Mellitus: A Systematic Review.

To evaluate and synthesize evidence on the impact of educational interventions for individuals with insulin-treated type 2 diabetes mellitus (T2DM). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, five electronic databases (Scopus, PubMed, Medline, CINAHL Plus with Full Text, and Web of Science) were systematically searched in February 2024. The search focused on studies published between 2019 and 2024 that investigated the impact of educational interventions on individuals with insulin-treated T2DM. Reference lists of the included studies were also manually searched. Titles and abstracts were screened for eligibility, and relevant full texts were assessed. Out of 1,032 identified records, 11 studies met the inclusion criteria. According to the data synthesized using a convergent integrated analysis framework, five major themes have emerged: 1) Glycemic control (including subthemes improving HbA1C, decreasing postprandial plasma glucose, and decreasing fasting plasma glucose), 2) Insulin-related complications (including subthemes reducing hypoglycemic events and reducing the size of lipohypertrophy), 3) Knowledge, Attitude, and Practice (including subthemes engaging in self-management, improving insulin injection technique, improving knowledge, and improving attitude toward insulin treatment), 4) Optimal dose of insulin, and 5) Improving quality of life. Educational interventions are crucial for improving diabetes-related outcomes and reducing complications in individuals with insulin-treated T2DM. These interventions enhance knowledge, attitudes, and self-management practices, leading to better glycemic control and quality of life. Healthcare settings should develop and provide tailored educational programs for individuals with insulin-treated T2DM to optimize outcomes and minimize complications.

Exploring potential risk factors for lower limb amputation in people with diabetes-A national observational cohort study in Sweden.

Risk factors for lower limb amputation (LLA) in individuals with diabetes have been under-studied. We examined how 1/demographic and socioeconomic, 2/medical, and 3/lifestyle risk factors may be associated with LLA in people with newly diagnosed diabetes. Using the Swedish national diabetes register from 2007 to 2016, we identified all individuals ≥18years with an incident diabetes diagnosis and no previous amputation. These individuals were followed from the date of diabetes diagnosis to amputation, emigration, death, or the end of the study in 2017 using data from the In-Patient Register and the Total Population Register. The cohort consisted of 66,569 individuals. Information about demographic, socioeconomic, medical, and lifestyle risk factors was ascertained around the time of the first recorded diabetes diagnosis, derived from the above-mentioned registers. Cox proportional hazard models were used to obtain hazard ratios (HR) with 95% confidence intervals (CI). During the median follow-up time of 4years, there were 133 individuals with LLA. The model adjusting for all variables showed a higher risk for LLA with higher age, HR 1.08 (95% CI 1.05-1.10), male sex, HR 1.57 (1.06-2.34), being divorced, HR 1.67 (1.07-2.60), smokers HR 1.99 (1.28-3.09), insulin treated persons HR 2.03 (1.10-3.74), people with low physical activity (PA) HR 2.05 (1.10-3.74), and people with an increased foot risk at baseline HR>4.12. People with obesity had lower risk, HR 0.46 (0.29-0.75). This study found a higher risk for LLA among people with higher age, male sex, who were divorced, had a higher foot risk group, were on insulin treatment, had lower PA levels, and were smokers. No significant association was found between risk for LLA and education level, country of origin, type of diabetes, blood glucose level, hypertension, hyperlipidemia, creatinine level, or glomerular filtration rate. Obesity was associated with lower risk for LLA. Identified variables may have important roles in LLA risk among people with diabetes.

Comparison of the effects of losartan potassium and benazepril in the treatment of hypertensive patients with insulin resistance.

To compare the efficacy of losartan potassium (LP) and benazepril in the treatment of hypertensive patients with insulin resistance (IR). This is a retrospective analysis of the clinical data of 155 hypertensive patients with IR admitted to Shanghai Pudong New Area People's Hospital from March 2021 to March 2023. Of these 76 received LP treatment (LP group), and 79 received benazepril treatment (benazepril group). Blood pressure levels, blood glucose and insulin levels, treatment efficacy, and incidence of adverse reactions before and after the treatment in both groups were compared. After the treatment, diastolic and systolic blood pressure in the two groups significantly decreased compared to pre-treatment levels (P<0.05), with no significant difference between the two groups (P>0.05). After the treatment, levels of fasting plasma glucose (FPG), 2-hours plasma glucose (2hPG), fasting insulin (FINS), 2-hours insulin (2hINS), and insulin sensitivity index (ISI) in both groups significantly decreased compared to pre-treatment levels (P<0.05), with no significant difference between the two groups (P>0.05). There was no significant difference in the total efficacy and the incidence of adverse reactions between the two groups (P>0.05). The efficacy of LP and benazepril in treating hypertension with IR is equivalent. Both are safe and can effectively lower blood sugar and insulin levels, alleviate IR, and lower blood pressure.

Effect of intranasal insulin on perioperative cognitive function in older adults: a randomized, placebo-controlled, double-blind clinical trial.

Postoperative cognitive impairment are common neural complications in older surgical patients and exacerbate the burden of medical care on families and society. A total of 140 older patients who were scheduled for elective orthopaedic surgery or pancreatic surgery with general anaesthesia were randomly assigned to Group S or Group I with a 1:1 allocation. Patients in Group S and Group I received intranasal administration of 400μL of normal saline or 40IU/400μL of insulin, respectively, once daily from 5minutes before anaesthesia induction until 3days postoperatively. Perioperative cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Basic (MoCA-B) at 1day before and 3days after surgery and postoperative delirium (POD) incidence was assessed using the 3-minute Diagnostic Interview for CAM (3D-CAM) on postoperative days 1-3. Serum levels of interleukin-6 (IL-6), tumour necrosis factor α (TNF-α), S100-β and C-reactive protein (CRP) were measured on the first day after surgery. Insulin treatment significantly increased postoperative MMSE and MoCA-B scores in group I than in group S (P < 0.001, P = 0.001, respectively), decreased the incidence of POD within the 3-day postoperative period in Group I than in Group S (10.9% vs 26.6%, P = 0.024), and inhibited postoperative IL-6 and S100-β levels in Group I compared to Group S (P = 0.034, P = 0.044, respectively). Intranasal insulin administration is thus suggested as a potential therapy to improve postoperative cognition in older patients undergoing surgery. However, a more standardized multi-centre, large-sample study is needed to further validate these results.

Comparative efficacy of therapeutic plasma exchange and insulin in hypertriglyceridemia-induced acute pancreatitis.

Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) presents a therapeutic challenge with no currently definitive treatment, including therapeutic plasma exchange (TPE) and insulin. TPE aims to quickly reduce serum triglyceride (TG); however, its efficacy lacks convincing evidence. Intravenous insulin is a promising and convenient alternative, while comparative data is limited. This retrospective, single-center study compared TPE and insulin treatment in HTG-AP patients. The primary outcome measured was the percentage of TG reduction within 48hours of admission. The study included 33 TPE-treated and 56 insulin-treated patients. The TPE groups were more severe than those with medical therapy at baseline characteristics. A trend towards higher TG reduction within 24hours was observed in the TPE group (62.5% [IQR 51.7-83.3] vs. 55.7% [IQR 34.2-74.7], p = 0.038). However, no significant difference in TG reduction at 48hours was found between insulin and TPE groups (83.6% and 81.9%, respectively, p = 0.715). The TPE group exhibited extended hospital stays (10.0 [IQR 7.0-13.5] days vs. 6.0 [4.0-8.7] days, p = 0.001) without any difference in in-hospital mortality or time needed to lower TG below < 11.3mmol/L. In patients with HTG-AP, TPE decreased plasma triglyceride levels faster in the first 24hours than insulin therapy. However, there was no significant advantage after 48hours. Therefore, insulin may be a promising alternative and convenient treatment in carefully selected patients with HTG-AP.

Mechanisms of insulin resistance in type 1 diabetes mellitus: A case of glucolipotoxicity in skeletal muscle.

Insulin resistance (IR), a hallmark of type 2 diabetes mellitus, develops in a significant number of patients with type 1 diabetes mellitus (T1DM) despite the use of insulin therapy to control glycemia. However, little is currently understood regarding the underlying mechanisms of IR in T1DM, especially within the context of chronic insulin treatment. Recent evidence suggests an important influence of glucolipotoxicity in skeletal muscle on insulin sensitivity in T1DM. Thus, this review summarizes our current knowledge regarding impairments in skeletal muscle lipid, glucose, and oxidative metabolism in the development of IR in insulin-treated T1DM.

Long-term GABA Supplementation Regulates Diabetic Gastroenteropathy through GABA Receptor/trypsin-1/PARs/Akt/COX-2 Axis.

Molecular alterations of diabetic gastroenteropathy are poorly identified. This study investigates the effects of prolonged GABA supplementation on key protein expression levels of trypsin-1, PAR-1, PAR-2, PAR-3, PI3K, Akt, COX-2, GABAA, and GABAB receptors in the gastric tissue of type 2 diabetic rats (T2DM). To induce T2DM, a 3-month high-fat diet and 35 mg/kg of streptozotocin was used. Twenty-four male Wistar rats were divided into 4 groups: (1) control, (2) T2DM, (3) insulin-treated (2.5 U/kg), and (4)GABA-treated (1.5 g/kg GABA). Blood glucose was measured weekly. The protein expressions were assessed using western blotting. Histopathological changes were examined by H&E and Masson's staining. Diabetic rats show reduced NOS1 and elevated COX-2 and trypsin-1 protein expression levels in gastric tissue. Insulin and GABA therapy restored the NOS1 and COX-2 levels to control values. Insulin treatment increased PI3K, Akt, and p-Akt and, decreased trypsin-1, PAR-1, PAR-2, and PAR-3 levels in the diabetic rats. Levels of GABAA and GABAB receptors normalized following insulin and GABA therapy. H&E staining indicated an increase in mucin secretion following GABA treatment. These results suggest that GABA by acting on GABA receptors may regulate the trypsin-1/PARs/Akt/COX-2 pathway and thereby improve complications of diabetic gastroenteropathy.

Leptin and insulin synergize with PIK3CA mutation to enhance PD-L1 mediated immunosuppression in thyroid cancer

The incidence of thyroid cancer keeps rising and obesity emerges as an important risk factor for thyroid cancer, but the underlying mechanism is far from clear. Here, we hypothesize that leptin and insulin, two hormones closely related to obesity, may contribute to the pathogenesis of thyroid cancer. By using a combination of assays like CRISPR KO, cancer cell-T cell co-culture, ApoLive-Glo™ multiplex assay and syngeneic mouse model, we show that PD-L1 protein levels are increased dose-dependently by leptin or insulin in multiple thyroid cancer cell lines. Leptin and insulin converge to activate the PI3K-AKT pathway to enhance PD-L1 expression and activity. In addition, we use CRISPR KO to generate human thyroid cancer cells expressing WT PIK3CA or PIK3CA-E545K mutant. PIK3CA- E545K mutation makes the thyroid cancer cells to produce more PD-L1 protein upon leptin or insulin treatment. Thus, leptin and insulin synergize with PIK3CA mutation to enhance PD-L1 expression. Dual blockade of leptin and insulin signaling pathways reduces tumor size in a syngeneic mouse model. Our study suggests that understanding the interaction between genetic mutation and obesity is crucial for comprehensively assessing thyroid cancer risk and developing effective treatment strategies.

Liraglutide enhances insulin secretion and prolongs the remission period in adults with newly diagnosed type 1 diabetes (the NewLira study): A randomized, double-blind, placebo-controlled trial.

To test the effect of the glucagon-like peptide-1 receptor agonist, liraglutide, on residual beta-cell function in adults with newly diagnosed type 1 diabetes. In a multicentre, double-blind, parallel-group trial, adults with newly diagnosed type 1 diabetes and stimulated C-peptide of more than 0.2 nmol/L were randomized (1:1) to 1.8-mg liraglutide (Victoza) or placebo once daily for 52 weeks with 6 weeks of follow-up with only insulin treatment. The primary endpoint was the between-group difference in C-peptide area under the curve (AUC) following a liquid mixed-meal test after 52 weeks of treatment. Sixty-eight individuals were randomized. After 52 weeks, the 4-hour AUC C-peptide response was maintained with liraglutide, but decreased with placebo (P = .002). Six weeks after end-of-treatment, C-peptide AUCs were similar for liraglutide and placebo. The average required total daily insulin dose decreased from 0.30 to 0.23 units/kg/day with liraglutide, but increased from 0.29 to 0.43 units/kg/day in the placebo group at week 52 (P < .001). Time without the need for insulin treatment was observed in 13 versus two patients and lasted for 22 weeks (from 3 to 52 weeks) versus 6 weeks (from 4 to 8 weeks) on average for liraglutide and placebo, respectively. Patients treated with liraglutide had fewer episodes of hypoglycaemia compared with placebo-treated patients. The adverse events with liraglutide were predominantly gastrointestinal and transient. Treatment with liraglutide improves residual beta-cell function and reduces the dose of insulin during the first year after diagnosis. Beta-cell function was similar at 6 weeks postliraglutide treatment.

Impact of triple transmembrane regulator therapy on glucose metabolism in cystic fibrosis related diabetes during clinical practice

AimsTo evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on Cystic Fibrosis Related Diabetes (CFRD) glycemic control and insulin treatment in patients with CFRD during clinical practice. MethodsWe carried out a retrospective observational study of 23 adult patients with CFRD who started treatment with ETI. They had, at least, one F508del mutation. Data were collected before ETI initiation and 3, 6, and 12 months after. ResultsGlycemic control measured by HbA1c significantly improved by 0.3 % (0.1–0.5) after 3 months of ETI therapy (p = 0.004) and kept this improvement during follow-up (p < 0.001). The proportion of patients needing multiple daily injections of insulin was reduced by 16 % (p = 0.023). Total daily insulin dose dropped by 0.12 (0.05–0.18) UI/kg/day (p < 0.001). Data derived from Flash Continuous Glucose Monitoring (CGM) for patients treated with insulin stayed unchanged after insulin reduction, except for a significant 8 % (0.3–15.6) increase in the Time In Tight Range (TITR) between 70 and 140 mg/dL (p = 0.043). ConclusionETI therapy impacted CFRD in clinical practice reducing insulin needs and improving glycemic control measured by HbA1c and CGM. The improvements can be observed from the first 3 months of treatment.

A Review of Stage 0 Biomarkers in Type 1 Diabetes: The Holy Grail of Early Detection and Prevention?

Type 1 diabetes mellitus (T1D) is an incurable autoimmune disease characterized by the destruction of pancreatic islet cells, resulting in lifelong dependency on insulin treatment. There is an abundance of review articles addressing the prediction of T1D; however, most focus on the presymptomatic phases, specifically stages 1 and 2. These stages occur after seroconversion, where therapeutic interventions primarily aim to delay the onset of T1D rather than prevent it. This raises a critical question: what happens before stage 1 in individuals who will eventually develop T1D? Is there a "stage 0" of the disease, and if so, how can we detect it to increase our chances of truly preventing T1D? In pursuit of answers to these questions, this narrative review aimed to highlight recent research in the field of early detection and prediction of T1D, specifically focusing on biomarkers that can predict T1D before the onset of islet autoimmunity. Here, we have compiled influential research from the fields of epigenetics, omics, and microbiota. These studies have identified candidate biomarkers capable of predicting seroconversion from very early stages to several months prior, suggesting that the prophylactic window begins at birth. As the therapeutic landscape evolves from treatment to delay, and ideally from delay to prevention, it is crucial to both identify and validate such "stage 0" biomarkers predictive of islet autoimmunity. In the era of precision medicine, this knowledge will enable early intervention with the potential for delaying, modifying, or completely preventing autoimmunity and T1D in at-risk children.

Male Akita diabetic mice develop underactive bladder independent of NLRP3 that can be prevented with blood glucose control

Aim:Diabetic bladder dysfunction (DBD) is the most common diabetic complication. Patients present with overactive symptoms, underactive symptoms, or both. While strict glucose control may be expected to reverse DBD, prior studies have not been supportive. However, we hypothesize that strict control, soon after hyperglycemia appears, can prevent DBD development. Moreover, 50% of adult diabetics are poorly-controlled and it is unknown how this effects development of DBD. Thus, we investigated the effect of early glucose control (poor and strict) on DBD in male Akita diabetic mice (type 1). NLRP3-induced inflammation is critical to development of DBD in female Akita. Therefore, we also hypothesized that targeting NLRP3 may control or prevent DBD in male Akita, especially in a poorly-controlled population. Methods:Akita mice (±NLRP3) were stratified into uncontrolled, poorly-controlled and strictly-controlled diabetic groups using insulin treatment (0, 0.125 or 0.25 U/day). Mice were assessed at 15 weeks for blood glucose, HbA1c, Evans blue dye extravasation (a marker of capillary permeability/inflammation) and bladder function. Results:Blood glucose was elevated in diabetics, reduced in an insulin dose-dependent manner, and not affected by NLRP3 deletion. HbA1c levels followed a similar course but were more sensitive to insulin levels. Evans blue dye extravasation was prevented with glucose control and absent in NLRP3−/− mice. Diabetics exhibited signs of underactive bladder (increased void volume, decreased frequency) that was attenuated in the uncontrolled group but absent in the well-controlled group. Deleting NLRP3 did not affect voiding function. Conclusion:Male Akita mice develop an underactive-like bladder, independent of NLRP3, which can be prevented with glucose control.

PI3KR1 and AKT1 in largemouth bass (Micropterus salmoides): molecular cloning, characterization, and its involvement in the alleviation of hepatic glycogen deposition caused by insulin inclusion in vitro.

In this study, the full-length cDNA sequences of the phosphatidylinositol-3-kinase p85 alpha (PI3KR1) and serine/threonine kinase 1 (AKT1) genes in largemouth bass (Micropterus salmoides) were obtained using the rapid amplification of cDNA ends (RACE) method. Sequence analysis revealed that the cloned sequences of PI3KR1 and AKT1 are 4170 bp and 3672 bp in length, with open reading frames (ORFs) of 1389 bp and 1422 bp encoding 462 and 473 amino acids, respectively. Sequence alignment and evolutionary tree analysis indicated their close relationship to other teleosts, especially those with similar feeding habits. Tissue distribution demonstrated widespread distribution of both genes in various tissues, with the highest abundance in the liver. Further results found that the upregulation of the expression of p-PI3KR1, p-AKT1, p-FoxO1, and GLUT2 proteins by insulin, while suppressing the expression of the total FoxO1 protein, effectively triggers a significant activation of the PI3KR1-AKT1 insulin signaling pathway. Meanwhile, the mRNA levels of the key glycolytic genes, including glucokinase (gk), pyruvate kinase (pk), and phosphofructokinase liver type (pfkl), have been enhanced evidently. In contrast, the expression of gluconeogenic genes such as phosphoenolpyruvate carboxykinase (pepck), glucose-6-phosphatase catalytic subunit (g6pc), and fructose-1,6-bisphosphatase-1 (fbp1) has been notably down-regulated. In addition, insulin treatment promoted the phosphorylation of glycogen phosphorylase (PYGL) and the dephosphorylation of glycogen synthase (GS), and the glycogen content in the insulin-treated group was remarkably reduced compared to the control group. Overall, our study indicates that the activation of PI3KR1-AKT1 insulin signaling pathway represses the hepatic glycogen deposition via the regulation of glycolysis and gluconeogenesis, which provides some new insights into nutritional strategy to effectively regulate the glucose metabolism in carnivorous fish.

Neonatal outcomes of gestational diabetes mellitus (GDM) mothers: A cross-sectional study comparing medical nutritional therapy, metformin, and insulin treatments at a tertiary care centre

Gestational Diabetes Mellitus (GDM) poses a rising global health challenge, affecting 10-14.3% of pregnant women. This study aimed to investigate and compare neonatal outcomes among mothers with GDM treated with Medical Nutritional Therapy (MNT), metformin, and insulin at a tertiary care center. Understanding the impact of these treatments on neonatal outcomes is crucial for optimal care.Conducted at a tertiary care center in Chennai, India, this cross-sectional study included 160 GDM mothers identified through medical records from December 2021 to December 2023. Inclusion criteria covered women aged 18 and above, experiencing singleton pregnancies, diagnosed with GDM, and maintaining regular follow-up. Data analysis included birth weight, Apgar scores, neonatal hypoglycemia, and preterm birth rates. Multinomial logistic regression determined adjusted odds ratios.The study analyzed the distribution of perinatal factors among 160 neonates, revealing that 41.3% were delivered vaginally, while 58.8% were through cesarean section. The majority were preterm, with 118 being appropriate for gestational age.Neonatal Intensive Care Unit (ICU) admission was noted in 34.4% of cases, while 62.7% did not. Neonatal hypoglycemia was observed in 36.3% of cases, and seizures were present in 19.4%. Apgar scores were low in 23.8% of cases.A multinomial logistic analysis found that the Metformin, Insulin, and Metformin + Insulin groups had significantly higher odds of having a Cesarean section compared to the diet-only group. However, the Metformin group had lower odds of preterm birth, NICU admission, neonatal hypoglycemia, seizures, and AGA. The Metformin group had higher odds of LGA and Apgar score &amp;#60;7 at both the 1st and 5th minutes. No significant differences were found in the odds of preterm birth, NICU admission, or seizures between the diet-only and Metformin groups.This pioneering South Indian study of 160 neonates born to GDM mothers compared different treatment options. Metformin, alone or with insulin, showed comparable neonatal outcomes to insulin. Caution in GDM deliveries is recommended for optimal well-being. The study emphasizes the need for further research considering maternal outcomes as potential confounders to comprehensively understand GDM treatments and neonatal outcomes.

Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes.

Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus (T2DM), that is, patients who have insulin resistance, obesity, and other cardiovascular risk factors, suggesting that the presence of glutamic acid decarboxylase (anti-GAD65), islet antigen 2 (anti-IA2), and zinc transporter 8 (anti-Zn8T) antibodies could have deleterious effects on beta cell function, causing failure and earlier requirement for insulin treatment. To evaluate anti-GAD65, anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of T2DM. This was a case-control study in patients with clinically diagnosed with T2DM (68 cases and 64 controls with and without early insulin dependence respectively), male and female, aged 12-18 years. Somatometry, blood pressure, glucose, insulin, C-peptide, glycated hemoglobin A1c, and lipid profiles were assessed. ELISA was used to measure anti-GAD65, anti-IA2, and anti-Zn8T antibodies. Descriptive statistics, Pearson's χ 2 test, Student's t test, and logistic regression was performed. P < 0.05 was considered statistically significant. There were 132 patients (53.8% female), with a mean age was 15.9 ± 1.3 years, and there was a disease evolution time of 4.49 ± 0.88 years. The presence of anti-GAD65, anti-IA2, and anti-Zn8T positivity was found in 29.5%, 18.2%, and 15.9%, respectively. Dividing the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity: anti-GAD65 odds ratio (OR): 2.42 (1.112-5.303, P = 0.026); anti-IA2: OR: 1.55 (0.859-2.818, P = 0.105); and anti-Zn8T: OR: 7.32 (2.039-26.279, P = 0.002). Anti-GAD65 positivity was high in our study. Anti-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype, leading to an increased risk of early insulin dependence.

Health Outcome Changes in Individuals With Type 1 Diabetes After a State-Level Insulin Copayment Cap

Many insulin users ration doses due to high out-of-pocket costs. Starting January 2020 with Colorado, 25 states and the District of Columbia enacted laws that cap insulin copayments. To estimate the association of Colorado's $100 copayment cap with out-of-pocket spending, medication adherence, and health care services utilization for diabetes-related complications. In this cohort study using Colorado's All-Payer Claims Database, nonelderly insulin users with type 1 diabetes were analyzed from January 2019 to December 2020. Outcome changes were compared in the prepolicy and postpolicy period among individuals continuously enrolled in state-regulated and non-state-regulated plans using difference-in-differences regressions. Subgroup analyses were conducted based on individuals' prepolicy spending (low: never ≥$100 out-of-pocket vs high: ≥$100 out-of-pocket cost at least once). Data were analyzed from June 2023 to May 2024. Enrollment in state-regulated health insurance plans subject to the copayment cap legislation. Adherence to basal and bolus insulin treatment was evaluated using the proportion of days covered measure, out-of-pocket spending reflected prescription cost for a 30-day supply, and health care utilization for diabetes-related complications was identified using primary diagnosis codes from medical claims data. The panel included 1629 individuals with type 1 diabetes (39 096 person-months), of which 924 were male (56.7%), 540 (33.1%) had 1 or more comorbidities, and the mean (SD) age was 40.6 (15.9) years. Overall, the copayment cap was associated with out-of-pocket spending declines of $17.3 (95% CI, -$27.3 to -$7.3) for basal and $11.5 (95% CI, -$24.7 to $1.7) for bolus insulins and increases in adherence of 3.2 (95% CI, 0.0 to 6.5) percentage points for basal and 3.3 (95% CI, 0.3 to 6.4) percentage points for bolus insulins. Changes in adherence were associated with increases within the prepolicy high-spending group (basal, 9.9; 95% CI, 2.4 to 17.4 percentage points; bolus, 13.0; 95% CI, 5.1 to 20.9 percentage points). The policy was also associated with a mean reduction of -0.09 (95% CI, -0.16 to -0.02) medical claims for diabetes-related complications per person per month among high spenders, a 30% decrease. In this cohort study of Colorado's insulin copayment cap among individuals with type 1 diabetes, the policy was associated with an overall decline in out-of-pocket spending, an increase in medication adherence, and a decline in claims for diabetes-related complications only among insulin users who spent more than $100 in the prepolicy period at least once.

β-cell function and long-term glycemic control in patients newly diagnosed with type 2 diabetes with moderate hyperglycemia after a 6-month course of basal insulin therapy

AimsTo evaluate whether treatment with insulin is advantageous compared with oral anti-diabetic drugs (OAD) for patients newly diagnosed with type 2 diabetes with moderate hyperglycemia. MethodsPatients newly diagnosed with type 2 diabetes with moderate hyperglycemia were recruited and randomized to receive insulin, metformin or sitagliptin treatment. The oral glucose tolerance test (OGTT) was performed before treatment and 6 months thereafter. The primary outcome was the glycohemoglobin (HbA1c) level change. For the secondary efficacy analysis, the β-cell function and insulin sensitivity were calculated from the OGTT, as was the proportion of subjects who reached the treatment target (HbA1c level < 7.0 % or < 6.5 %) at 6 months. ResultsWe randomized 50 patients to the three groups and 32 patients who received the allocated treatment were analyzed. The change of HbA1c level in the insulin, metformin, and sitagliptin groups was − 2.06 ± 1.37 %, −0.43 ± 0.32 %, and − 1.62 ± 0.92 %, respectively. This change was smallest in the metformin group. There was no significant difference in the changes or final HbA1c levels between the insulin and sitagliptin groups. The treat-to-target (HbA1c level < 7.0 %) rates in the insulin, metformin and sitagliptin were 75 %, 50 % and 100 %, respectively. The treat-to-target rates were not significantly different among the three groups. The insulin secretion indices, including the Matsuda index and HOMA-IR, indicated that the groups did not differ after 6 months of therapy. ConclusionA 6-month course of basal insulin therapy did not benefit patients newly diagnosed with diabetes with moderate hyperglycemia in terms of insulin sensitivity or insulin secretion.

The Prescription and Safety of Oral Antidiabetic Drugs in Outpatients with Type 2 Diabetes Mellitus: An Observational, Retrospective, Multicenter Study on the Role of Adherence in a Real-Life Primary Care Setting

Introduction: Type 2 diabetes mellitus (T2DM) is a common disease burdened with significant morbidity and mortality. Despite the substantial number of new available drug treatments, adherence to therapy and adverse drug reactions (ADRs) are the major constraint in the management of this disease. We evaluated the use, the adherence, and the safety of antidiabetic drugs in patients with T2DM. Methods: We performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners in Catanzaro (Calabria, Italy). Drug adherence was measured considering the packages of antidiabetic drugs prescribed at the time of admission, after three months, and 1 year later. ADRs were evaluated using the Naranjo probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study, we evaluated 12,170 medical records of seven general practitioners. The most prescribed drug was metformin alone (28.4%) or with other oral antidiabetics (19.6%) and then insulin (n: 354; men 190, women 164). Logistic regression showed an association between T2DM less than or equal to 5 years and low adherence (p = 0.023). During the study, we recorded 26 ADRs that were correlated with sex (women) and insulin treatment. Conclusions: this real-life study shows that patients with T2DM have a high adherence, probably related to their having a low number of ADRs.