Improvement In Glycemic Control Research Articles

Genetic Evidence for GLP-1 and GIP Receptors as Targets for Treatment and Prevention of MASLD/MASH.

Glucagon-like peptide-1 receptor (GLP1R) agonists and glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists may help treat metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). However, their definitive effects are still unclear. Our study aims to clarify this uncertainty. We utilised conventional Mendelian randomisation (MR) analysis to explore potential causal links between plasma GLP-1/GIP concentrations and MASLD and its related traits. Next, we conducted drug-target MR analysis using highly expressed tissue data to assess the effects of corresponding drug perturbation on these traits. Finally, mediation analysis was performed to ascertain whether the potential causal effect is direct or mediated by other MASLD-related traits. Circulating 2-h GLP-1 and GIP concentrations measured during an oral glucose tolerance test showed hepatoprotective effects on MASLD risk (ORGLP-1 = 0.168 [95% CI 0.033-0.839], p = 0.030; ORGIP = 0.331 [95% CI 0.222-0.494], p = 6.31 × 10-8). GLP1R expression in the blood had a minimal causal effect on MASLD risk, whereas GIPR expression significantly affected MASLD risk (OR = 0.671 [95% CI 0.531-0.849], p = 9.07 × 10-4). Expression levels of GLP1R or GIPR in the blood significantly influenced MASLD-related clinical traits. Mediation analysis revealed that GIPR expression protected against MASLD, even after adjusting for type 2 diabetes or body mass index. GLP-1/GIP receptor agonists offer promise in lowering MASLD/MASH risk. GIP receptor agonists can exert direct and indirect effects on MASLD mediated by weight reduction or glycemic control improvement.

Use of Technology in the Management and Treatment of Prediabetes, A New Era: A Case Report Series

Introduction: The escalating prevalence of prediabetes has positioned it as a silent precursor to a looming public health crisis, particularly as it paves the way for type 2 diabetes mellitus (T2DM). This case series report explores the transformative role of technology, specifically the Sugar Fit’s Diabetes Reversal and Management Program (SDRMP), in the treatment and management of prediabetic patients. Methods: The case series follows the progress of two patients aged 31-44 with prediabetes utilizing the SDRMP to prevent the progression to diabetes. The interventions for both patients involved continuous glucose monitoring, personalized nutrition plans, fitness strategies, and behavioral modifications. The patients also engaged in regular communication with their life coaches through the Sugar Fit application, ensuring ongoing support and adherence to the program. Results: The results revealed significant improvements in glycemic control, lipid profiles, and overall well-being. The first patient, a 44-year-old male, demonstrated a successful return to normal glycemic control in 177 days through a comprehensive approach involving dietary changes, exercise, and lifestyle modifications. The second patient, a 31-year-old male, achieved normal glycemic control in a comparable timeframe, showcasing the effectiveness of the SDRMP. Discussion and Conclusion: These cases demonstrate that patients were able to adhere to the goals of care, preventing the progression of prediabetes to diabetes and improving insulin resistance. The study also underscores the potential impact of technology on public health outcomes, bridging the gap between traditional interventions and the evolving needs of a tech-savvy population. The synergy between healthcare expertise and technological innovation not only arrests the progression of prediabetes but also contributes to a broader societal shift towards metabolic well-being, paving the way for a healthier future. Future monitoring is essential to ensure the maintenance of lifestyle modifications and continued success in preventing diabetes.

Twelve-Month Real-World Use of an Advanced Hybrid Closed-Loop System Versus Previous Therapy in a Dutch Center For Specialized Type 1 Diabetes Care.

Complexity of glucose regulation in persons with type 1 diabetes (PWDs) necessitates increased automation of insulin delivery (AID). This study aimed to analyze real-world data over 12 months from PWDs who started using the MiniMed 780G (MM780G) advanced hybrid closed-loop (aHCL) AID system at the Diabeter clinic, focusing on glucometrics and clinical outcomes. Persons with type 1 diabetes switching to the MM780G system were included. Clinical data (e.g. HbA1c, previous modality) was collected from Diabeter's electronic health records and glucometrics (time in range [TIR], time in tight range [TITR], time above range [TAR], time below range [TBR], glucose management indicator [GMI]) from CareLink Personal for a 12-month post-initiation period of the MM780G system. Outcomes were age-stratified, and the MM780G system was compared with previous use of older systems (MM640G and MM670G). Longitudinal changes in glucometrics were also evaluated. A total of 481 PWDs were included, with 219 having prior pump/sensor system data and 334 having monthly longitudinal data. After MM780G initiation, HbA1c decreased from 7.6 to 7.1% (P < .0001) and the percentage of PWDs with HbA1c <7% increased from 30% to 50%. Glucose management indicator and TIR remained stable with mean GMI of 6.9% and TIR >70% over 12 months. Age-stratified analysis showed consistent improvements of glycemic control across all age groups, with older participants achieving better outcomes. Participants using recommended system settings achieved better glycemic outcomes, reaching TIR up to 77% and TTIR up to 55%. Use of MM780G system results in significant and sustained glycemic improvements, consistent across age groups and irrespective of previous treatment modalities.

Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review

The history of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is so long and started in 1835 when Petersen extracted a compound called phlorizin from apple tree bark. About fifty years later, von Mering discovered its glucosuric properties. In the 1980s, it was discovered that the glucosuria resulted from inhibition by phlorizin of glucose reabsorption by the renal tubules, which lowered blood glucose levels in diabetic rats. Nowadays, beyond their glucose-lowering effects, growing evidence suggests significant cardiorenal benefits associated with SGLT2i therapy. Indeed, several clinical trials, including landmark studies such as EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, have demonstrated robust reductions in cardiovascular events, particularly heart failure hospitalizations and cardiovascular mortality, among patients treated with SGLT2i. However, subsequent trials showed that SGLT2i benefits extend beyond the diabetic population, encompassing individuals with and without diabetes. Additionally, SGLT2i exhibit nephroprotective effects, manifesting as a slowing of the progression of chronic kidney disease and a reduction in the risk of end-stage kidney disease. The mechanisms underlying the cardiorenal benefits of SGLT2i are multifactorial and include improvements in glycemic control, reduction in arterial stiffness, modulation of inflammation and oxidative stress, reduction of intraglomerular pression and promotion of natriuresis and diuresis through inhibition of SGLT2 in the luminal brush border of the first segments of the proximal kidney tubule. This narrative review aims to explore the cardiorenal outcomes of SGLT2i, encompassing their mechanisms of action, clinical evidence, safety profile, and implications for clinical practice.

Eighteen-Month Hybrid Closed-Loop Use in Very Young Children With Type 1 Diabetes: A Single-Arm Multicenter Trial.

We aimed to evaluate the longer-term safety and efficacy of hybrid closed-loop (CL) therapy in very young children with type 1 diabetes (T1D). Following a 16-week multinational, randomized crossover trial comparing hybrid CL with sensor-augmented pump (SAP) therapy in 74 very young children aged 1-7 years with T1D, participants were invited to an extension phase using CL for a further 18 months. Outcomes were compared with the primary-phase SAP period and primary-phase CL period. After the primary study phase, 60 participants were eligible to enroll in the extension. Of these, 49 consented (mean ± SD age 6.6 ± 1.5 years) to continue use of CL for 18 months. Percentage time in range (TIR) 3.9-10.0 mmol/L was 8.4 percentage points (95% CI 6.7 to 10.1; P < 0.001) higher, while HbA1c was 0.4% ([5.0 mmol/mol], 95% CI 0.3 to 0.6 [3.7 to 6.2]; P < 0.001) lower during the CL extension phase compared with primary-phase SAP period. At 18 months, mean HbA1c was 6.7 ± 0.5% and TIR was 70 ± 7%, compared with 6.7 ± 0.5% and 71 ± 6% in the primary-phase CL period. Time in hypoglycemia (<3.9 mmol/L) was similar between CL extension phase and both primary-phase SAP (P = 0.31) and CL periods (P = 0.70). There were two severe hypoglycemia events and one other serious adverse event during the extension phase. One unexpected serious adverse device effect occurred. Use of the Cambridge hybrid CL system led to sustained improvements in glycemic control lasting more than 18 months in very young children with T1D.

One-Year Effect of Elexacaftor/Tezacaftor/Ivacaftor Therapy on HbA1c Levels and Insulin Requirement in Patients with Insulin-Dependent Cystic Fibrosis-Related Diabetes: A Retrospective Observational Study.

The impact of ETI therapy on pulmonary function and nutritional status has been widely studied; the literature on the possible outcomes on glycemic control and insulin requirement in patients affected by CFRD is controversial. The main objective of our study was to evaluate HbA1c levels in patients with cystic fibrosis-related diabetes (CFRD) after one year of therapy with elexacaftor/tezacaftor/ivacaftor (ETI). The secondary objective was to study the changes in the total daily insulin dose (TDD), pulmonary function and metabolism in this population. A retrospective single-center observational study was conducted at the Regional Cystic Fibrosis Centre and Diabetology Centre of IRCCS Istituto Giannina Gaslini. The observation period was divided into four different time points: initiation (T0), 3 months (T3mo), 6 months (T6mo) and 12 months (T12mo) of ETI therapy. Demographic and clinical data were collected. The results were then stratified by genotype (homozygous or heterozygous F508del). Twenty-eight patients with CFRD undergoing insulin therapy were included. TDD (IU) significantly decreased at T3mo and T6mo, but not at T12mo, whereas HbA1c decreased significantly at all three times. The number of hospitalizations and pulmonary exacerbations decreased significantly. We demonstrated both improvement in glycemic control (by means of HbA1c) and insulin requirement in insulin-dependent CFRD patients after one year of ETI treatment.

A-9-Years-Old Female with Diabetes Mellitus Type 1 with Hyperthyroidism

Diabetes Mellitus Type 1 (DMT1) and thyroid disease can occur together, which is defined as a variant of autoimmune polyglandular syndrome type 3. It is known that the action of insulin and thyroid hormones affect cellular metabolism, thyroid hormones contribute to carbohydrate metabolism and pancreatic function. Since the thyroid gland plays a central role in the regulation of metabolism, abnormal thyroid function can have a major impact on the control of diabetes and poor glycemic control can cause alterations in thyroid hormone. A female, 9 years old, with decreased consciousness. Previous medical history, polyuria, increased appetite, and drastic weight loss. She also complained of sweating even in a cold room and was often emotional. On physical examination, there was fever, shortness of breath, tachycardia, and a soft and diffused slightly enlarged thyroid gland, with no bruit on auscultation. Laboratory tests showed blood glucose levels at 739 mg/dL, HbA1c 9.2%, C-peptide 0.2 ng/mL, TSH levels 0.01 µIU/mL, FT4 levels 2.77 ng/dL, the presence of metabolic acidosis, proteinuria, glucosuria, and ketonuria. Thyroid dysfunction will have a negative effect on DM control while poor glucose control will harm the work of thyroid hormones. Improvement in glycemic control and routine insulin injection with the right dose will reduce the risk of diabetic vascular and metabolic complications onset and progression.

12606 Gamification In The Management Of Children And Adolescents With Diabetes: A Systematic Review

Abstract Disclosure: L.C. Hespanhol: None. V. Lins de Menezes: None. P. Souto Maia: None. C.A. Balieiro: None. W. Oliveira Amador: None. R. Lira: None. Background: Educating children and adolescents with diabetes about their own condition presents a significant challenge. Gamification has been proposed as an innovative approach to ease the transition to self-care by engaging and empowering children and adolescents in their diabetes management. Purpose: The purpose of this systematic review is to examine published research on using gamification and technology within diabetes care for young patients. Methods: PubMed, Lilacs and EMBASE were systematically searched in January 2024 to include articles focusing on the use of new virtual technologies to improve the clinical and laboratory conditions of children and adolescents with diabetes. The protocol was registered in PROSPERO (ID: CRD42024499381) adhering to PRISMA recommendations. We assessed the risk of bias using RoB-2 and ROBINS-I. Results: A total of 24 studies were included, of which 7 were randomized trials. Age of participants ranged from 5 to 19 years. We identified five gamification strategies (i.e., applications, video games, minigame, robot, or web game) within seven clinical domains (i.e., psychosocial impairment, glycemic control, autonomy, reduced frequency of error, health lifestyle, nutrition, or knowledge about disease). 246 (27%) patients demonstrated reduced emotional distress and increased enjoyment. Reduction of errors such as hypoglycemia and emergency preparedness was identified in 354 (39%) of patients and improvement in glycemic control measured by HbA1c was described in 277 (30%) of patients. Conclusion: Our systematic review gamification has shown promise in fostering autonomy by providing tools that educate young individuals regarding glycemic control, lifestyle choices, injection practices, carbohydrate counting, and other pertinent aspects of diabetes management. Presentation: 6/1/2024

7518 A Case of Delayed Diagnosis of Acromegaly Associated with Uncontrolled Diabetes

Abstract Disclosure: A. Mahmoudabadi: None. S. Patel: None. Background: Acromegaly is a rare disorder characterized by an excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) levels, typically due to a GH-secreting pituitary adenoma. This consequently leads to complications such as acral and soft tissue overgrowth, visual disturbance, insulin resistance, and dyslipidemia. In this case, we describe a patient who presented to the endocrinology clinic for uncontrolled diabetes and was subsequently diagnosed with acromegaly. Clinical Case: This is a 47-year-old male with a history of heart failure, hypertension, and type 2 diabetes mellitus (DM) who presented to the clinic with uncontrolled DM. He had failed to achieve adequate blood sugar control despite being compliant with metformin, dapagliflozin, and insulin degludec. Physical examination revealed frontal bossing, prognathism, macroglossia, and a deep voice. On further questioning, he had noticed these changes since five years prior. Anthropometry and laboratory tests were as follows: Height, 180 cm; body weight 107.5 kg; body mass index (BMI), 33.05 kg/m2 and A1c level of 15.0%. Suspicion of acromegaly was confirmed based on biochemical and imaging findings. Fasting growth hormone (GH), at 58 mU/L (reference range 0-10), and insulin-like growth factor 1 (IGF-1), at 857 nmol/L (reference range 81-263), were markedly elevated. Pituitary magnetic resonance imaging (MRI) showed a sellar and suprasellar mass (2.6 × 2.2 × 2.2 cm) extending and compressing the optic chiasm. He eventually underwent a transsphenoidal adenomectomy with neurosurgery. Following surgery, his insulin requirements went from a total daily dose of about 100 units to an inpatient dose of 30 units by his last day of admission. Conclusion: Acromegaly is prevalent in less than 3% of patients with DM, but higher rates of DM are seen in acromegalic patients with higher IGF-1 levels and longer duration of disease. The diagnosis of acromegaly can often be delayed due to missed findings on routine physical examination. This can lead to increased morbidity, mortality, and complications such as uncontrolled DM, witnessed in our patient. Surgical management of acromegaly is the mainstay of treatment and can lead to improvement of glycemic control and insulin sensitivity. Fortunately, our patient could undergo surgery, but delayed diagnosis can prevent patients from surgery if the pituitary tumor becomes too large or unresectable. Ultimately, this case highlights the importance of a thorough physical examination and keeping a wide differential diagnosis when evaluating patients with uncontrolled DM, as failure to diagnose acromegaly at an early stage may have devastating consequences on patient outcomes. Presentation: 6/3/2024

Effect of weight-maintaining ketogenic diet on glycemic control and insulin sensitivity in obese T2D subjects

IntroductionLow carbohydrate ketogenic diets have received renewed interest for the treatment of obesity and type 2 diabetes. These diets promote weight loss, improve glycemic control, and reduce insulin resistance. However,...

The status of blood glucose monitoring and its influencing factors in Chinese patients with type 2 diabetes initiating premixed insulin: A prospective real-world study

ObjectiveThis study aimed to assess the current state of self-monitoring of blood glucose (SMBG) in Chinese patients initiating premixed insulin and its influential factors. Research Design and MethodsThis is a single-arm, multi-center, prospective real-world study enrolling a total of 8214 adult patients with type 2 diabetes mellitus (T2DM) newly initiated premixed insulin analogues. Each patient was followed up for 12 weeks, and the data related to SMBG was collected at week 1, week 4, week 8 and week 12, while data related to glycated hemoglobin were collected at week 1 and week 12. The primary outcome was the frequency of SMBG over 12 weeks. ResultsAt week 12, 83.3 % monitored blood glucose at least once, while 20.3 % of participants continued SMBG every week. The average monitoring frequency was 4.78 times/week over the first 4 weeks and 3.33 times/week over 12 weeks. The patients with a higher frequency of SMBG had better control of blood glucose. ConclusionsThis study found that most T2DM patients would take SMBG but the adherence decreased over time. The adherence to SMBG in Chinese T2DM patients was influenced by age, insulin dosage, education level, and diabetes duration. SMBG benefited the improvement of glycemic control.

Antidiabetic Treatment and Prevention of Ischemic Stroke: A Systematic Review

Background: Diabetes mellitus (DM) is a prevalent disease in the general population and also a well-established risk factor for the development of ischemic stroke. Patients who have been diagnosed with diabetes have a 20% higher risk for developing ischemic stroke in comparison to non-diabetic individuals. The aim of the current systematic review is to provide the latest evidence regarding the association between antidiabetic treatment and the prevention of ischemic stroke. Methods: A comprehensive search in scientific literature databases PUBMED, COCHRANE, and SCOPUS was conducted. The studies that were deemed as eligible for this review were those that examined the clinical benefits of therapeutic strategies in terms of preventing ischemic strokes. Results: A total of 32 studies met the established selection criteria. The included studies showed that pioglitazone treatment significantly reduced the risk for recurrent stroke in patients with DM. Furthermore, in the context of primary prevention, the improvement in glycemic control after treatment with the glucagon-like peptide-1 receptor agonists (GLP-1RA) semaglutide and dulaglutide was associated with a reduction in the risk of ischemic stroke in diabetic subjects. Metformin monotherapy may reduce stroke risk, while dipeptidyl peptidase 4 inhibitors, sodium-glucose co-transporter 2 inhibitors, and insulin do not seem to affect the incidence of stroke. Conclusions: The findings of the present systematic review suggest that pioglitazone and GLP-1RA may decrease the risk of stroke. Further studies are needed to provide additional data regarding the preventive effect of novel antidiabetic drugs, such as dual glucose-dependent insulinotropic polypeptide/GLP-1RA agents, on stroke.

Effects of Physical Activity on Patients With Diabetes Type 2: A Systematic Review

The aim of the research was to collect and to examine the positive effects of various physical activity (PA) programs on individuals with type 2 diabetes mellitus (T2DM). This included a combination of aerobic exercises and resistance training, with varying intensities, in order to compare which approach yielded better outcomes for T2DM management; This systematic review was conducted in line with PRISMA guidelines, focusing on the period from 1991 to 2024. Studies included in this review involved both experimental procedures and questionnaire-based surveys to assess the impact of PA on T2DM patients. The primary outcome was the effect of PA on T2DM, with secondary outcomes including changes in blood pressure, cholesterol levels, and glycemic control; A total of 23 studies, encompassing 1752 participants (515 men, 546 women, and 691 unspecified), met the inclusion criteria. The studies highlighted the positive effects of exercise, such as improvements in glycemic control, insulin sensitivity, and lipid profiles. Most studies recommended a combination of aerobic and resistance exercises performed 3-4 times per week for 30-60 minutes per session; This systematic review confirms that regular PA is instrumental in managing T2DM. Health care providers should integrate PA programs into treatment plans for T2DM patients to optimize glycemic control and overall health outcomes.

NOVOS ANTIDIABÉTICOS E PERSPECTIVAS NO MANEJO DA HIPERGLICEMIA CRÔNICA

The management of type 2 diabetes mellitus (T2DM) has evolved with the emergence of new oral and subcutaneous antidiabetic agents, which aim not only at glycemic control but also at the prevention of systemic complications. This study reviews the effects of new classes of hypoglycemic agents, such as SGLT-2 inhibitors, GLP-1 agonists, and insulin analogs, on chronic hyperglycemia control and complication prevention. An integrative literature review was conducted using the PubMed database, with articles published between 2019 and 2024, selected using the search key: ‘novel antidiabetic drugs’ OR ‘SGLT-2 inhibitors’ AND ‘chronic hyperglycemia’. Clinical trials and systematic reviews with full text in English were included. SGLT-2 inhibitors were found to be effective in reducing cardiovascular and renal events, along with a significant improvement in glycemic control. GLP-1 agonists and new combination therapies also demonstrated reductions in HbA1c levels and improvements in therisk profile for complications such as cardiovascular disease, diabetic nephropathy, and retinopathy. The inclusion of new devices, such as smart pens, has also contributed to individualized patient management. The introduction of new antidiabetic agents, with innovative mechanisms of action, has brought a significant advancement in the treatment of T2DM patients, aiding in complication prevention and optimizing glycemic control. The continued evolution of these therapies promises new perspectives in disease management.

NEW INSIGHTS INTO THE THIAZOLIDINEDIONES AS AN ADD-ON THERAPY TO METFORMIN AND GLIMEPIRIDE IN PATIENTS WITH UNCONTROLLED TYPE 2 DIABETES MELLITUS

Diabetes mellitus is a complex metabolic disorder that requires multifaceted management, including frequent blood glucose monitoring, polypharmacy, and timely therapeutic adjustments. Thiazolidinediones have been proposed as an effective add-on therapy to existing regimens to improve glycemic control in patients with Type 2 Diabetes Mellitus (T2DM). Objective: To evaluate the effectiveness of Thiazolidinediones as add-on therapy in diabetic patients already taking metformin and glimepiride. Methods: This observational, comparative, and follow-up cohort study was conducted in a tertiary care hospital in Pakistan. A total of 90 patients with poorly controlled T2DM were enrolled and randomly divided into two groups: Group A (n=45) received standard oral therapy with metformin and glimepiride, while Group B (n=45) received metformin, glimepiride, and Thiazolidinediones. The study outcomes included changes in Hemoglobin A1c (HbA1c), fasting blood sugar (FBS), and body mass index (BMI) throughout the study. Statistical analyses were performed using appropriate methods, with significance at p &lt; 0.05. Results: The addition of Thiazolidinediones in Group B resulted in superior glycemic control compared to Group A. Group B exhibited a 16.1% reduction in HbA1c versus an 8.2% reduction in Group A (p &lt; 0.05). FBS levels decreased by 28.8% in Group B compared to a 14.6% decrease in Group A (p &lt; 0.05). Additionally, BMI decreased by 1.5% in Group B, whereas Group A showed a slight increase of 0.06% (p &lt; 0.05). Significantly, the addition of Thiazolidinediones did not exacerbate the toxicity of the existing drug regimen. Conclusion: The study demonstrates that Thiazolidinediones, when added to standard therapy with metformin and glimepiride, offer significant improvements in glycemic control without additional toxicity. This combination therapy may be a beneficial strategy for managing poorly controlled Type 2 diabetes mellitus in the Pakistani population.

Long-Term Glycemic Control Improvement After the Home and Self-Care Program for Patients With Type 1 Diabetes: Real-World-Based Cohort Study.

The prevalence of type 1 diabetes (T1D) is increasing worldwide, with a much higher proportion of adult patients. However, achieving stable glycemic control is difficult in these patients. After periodic implementation of structured education for patients with T1D through the Home and Self-Care Program, a pilot home health care project promoted by the Korean government, we evaluated the program's effects on glycemic control. This study was conducted from April 2020 to March 2023. We analyzed 119 participants with T1D aged >15 years. Nursing and nutrition education were provided separately up to 4 times per year, with physician consultation up to 6 times per year. A distinguishing feature of this study compared with previous ones was the provision of remote support using a general-purpose smartphone communication app offered up to 12 times annually on an as-needed basis to enhance the continuity of in-person education effects. Patients were followed up on at average intervals of 3 months for up to 24 months. The primary end point was the mean difference in glycated hemoglobin (HbA1c) at each follow-up visit from baseline. For continuous glucose monitoring (CGM) users, CGM metrics were also evaluated. The mean HbA1c level of study participants was 8.6% at baseline (mean duration of T1D 10.02, SD 16.10 y). The HbA1c level reduction in participants who received at least 1 structured educational session went from 1.63% (SD 2.03%; P<.001; adjustment model=1.69%, 95% CI 1.24%-2.13% at the first follow-up visit) to 1.23% (SD 1.31%; P=.01; adjustment model=1.28%, 95% CI 0.78%-1.79% at the eighth follow-up visit). In the adjustment model, the actual mean HbA1c values were maintained between a minimum of 7.33% (95% CI 7.20%-7.46% at the first follow-up visit) and a maximum of 7.62% (95% CI 7.41%-7.82% at the sixth follow-up visit). Among CGM users, after at least 1 session, the mean time in the target range was maintained between 61.59% (adjusted model, 95% CI 58.14%-65.03% at the second follow-up visit) and 54.7% (95% CI 50.92%-58.48% at the eighth follow-up visit), consistently staying above 54.7% (corresponding to an HbA1c level of <7.6%). The mean time below the target range (TBR) also gradually improved to the recommended range (≤4% for TBR of <70 mg/dL and ≤1% for TBR of <54 mg/dL). The Home and Self-Care Program protocol for glycemic control in patients with T1D is effective, producing significant improvement immediately and long-term maintenance effects, including on CGM indexes.

Long-term TNF-alpha therapy for preserving beta cell function in new onset type 1 diabetes: a case report

BackgroundType 1 diabetes mellitus (T1D) is an autoimmune disease caused by destruction of pancreatic islet beta-cells. There is significant residual beta-cell function, measured through circulating C-peptide, present at the time of T1D diagnosis but this subsequently decreases with time. Higher residual beta-cell function at diagnosis associates with better glycaemic control and less glucose variability, and later in the disease course with less hypoglycaemia, lower glucose variability and fewer microvascular complications. There is therefore value in preserving residual beta cell function in new onset T1D Immunotherapeutic agents can protect residual beta-cell function in type 1 diabetes. However, clinical trials of such agents, whilst demonstrating C-peptide preservation in short term studies, have yet to be taken forward into routine clinical care due to concerns around safety and long-term efficacy. Here we report the case of a gentleman with newly diagnosed T1D whose glycaemic control and insulin requirement improved whilst on a five year infusion programme of infliximab, a monoclonal antibody against TNF-alpha, for colitis.Case presentationA 52-year-old White Caucasian man was diagnosed with T1D in August 2018. Glucose was 25.6 mmol/L, HbA1c was 98mmol/mol and GAD antibodies were strongly positive. HbA1c marginally improved to 91mmol/mol following initiation of insulin detemir 5 units at night and 1:10 g of insulin aspart (November 2018). In June 2019, he developed rectal bleeding and abdominal pain. Following colonoscopy, he was diagnosed with “indeterminate colitis” and commenced on 6-weekly infusions of 400-450 mg infliximab. Thus far, he has received 32 doses and achieved colitis remission. Following infliximab initiation there was increased frequency of mild-moderate hypoglycaemia and he was gradually weaned off and discontinued detemir in June 2020. Since then, HbA1c improved from 57mmol/mol in August 2019 to 52mmol/mol in April 2022, remaining stable at 51mmol/mol. His most recent HbA1c is 54mmol/mol in February 2024. His c-peptide was 550pmol/L in October 2022 and 442pmol/L in February 2024, suggesting well-preserved beta-cell function almost 6 years post-diagnosis.ConclusionsOur patient’s improvement in glycaemic control can be explained by immunomodulation and C peptide preservation from infliximab. With the growing focus on type 1 diabetes disease modulation and working towards an ‘insulin free T1D’, our findings strengthen the evidence base for the repurposing of and long-term treatment with anti-TNF-α agents to preserve beta-cell function in new onset T1D.

The Endogenous Inhibitor of CETP, apoC1, Remains Ineffective In Vivo after Correction of Hyperglycemia in People with Type 1 Diabetes.

ApolipoproteinC1 (apoC1) is the main physiological inhibitor of the cholesterol ester transfer protein (CETP). Increased CETP activity is associated with macrovascular complications in patients with type 1 diabetes (T1D). ApoC1 has lost its ability to inhibit CETP in patients with T1D, and in vitro glycation of apoC1 increases CETP activity, suggesting that hyperglycemia could be a factor implicated in the loss of the inhibitory effect of apoC1 on CETP. Thus, we aimed to see whether improvement of glycemic control might restore apoC1 inhibitory effect on CETP. We studied 98 patients with T1D and HbA1c > 9% at baseline and 3 months after improvement of glycemic control by a medical intervention (insulin introduction or changes in multi-injection therapy or pump therapy introduction/therapeutic education for all patients). CETP activity was assessed by a radioactive method and plasma apoC1 levels were measured by ELISA. The different isoforms of apoC1 were determined by mass spectrometry. CETP activity was not significantly modified after improvement of glycemic control, despite a significant reduction in mean HbA1c (8.7 ± 1.7 vs. 10.8 ± 2, p < 0.0001). No association between plasma apoC1 and CETP activity was observed in patients with T1D at baseline, nor at 3 months, even in the subgroup of patients with optimal control (3-month HbA1c < 7%). We did not find any glycated form of apoC1 using mass spectrometry in people with T1D. Hyperglycemia in vivo does not seem to be a major factor implicated in the loss of apoC1 ability to inhibit CETP activity observed in T1D. Other factors, such as qualitative abnormalities of lipoproteins, could be involved. Our data emphasize the fact that hyperglycemia is not the only factor involved in lipid abnormalities and macrovascular complications in T1D. Clinical trial reg. no. NCT02816099 ClinicalTrials.gov.

Effects of 12-weeks resistance training and vitamin E supplementation on aminotransferases, CTRP-2, and CTRP-9 levels in males with nonalcoholic fatty liver disease: a double-blind, randomized trial

BackgroundNonalcoholic fatty liver disease (NAFLD) involves excessive liver fat accumulation and is closely linked to oxidative stress, which contributes to liver inflammation and damage. This study aimed to evaluate how interventions such as resistance training (RT) and vitamin E supplementation (VES) can modulate markers of NAFLD and key proteins regulating glucose and lipid metabolism, such as C1Q/TNF-related proteins (CTRPs).MethodsForty participants with NAFLD (mean age: 32.4 ± 8.2 years) were randomly assigned to one of four groups for 12 weeks: placebo (PLB), VES, PLB + RT, and VES + RT. VES was administered at 800 IU/day in a double-blind manner. The RT regimen included eight exercises at 60–80% of one-repetition maximum (1RM), with three sets of 8–12 repetitions, performed three times per week. Pre- and post-intervention assessments included body composition, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lipid profile, glycemic control, CTRP-2, CTRP-9, and 1RM evaluations.ResultsFollowing the interventions, there was a significant improvement in body composition, lipid profile, glycemic control, and 1RM indices in the exercise groups compared to non-exercise groups (p < 0.05). AST and ALT levels decreased in all groups (p < 0.05) compared to the PLB group. There was also a significant difference between the VES + RT group and both the VES and PLB + RT groups (p < 0.05). CTRP-2 and CTRP-9 levels decreased in the exercise groups compared to non-exercise groups (p < 0.05), and their changes showed a marked correlation with body composition, lipid profile, and glycemic control indices (p < 0.05).ConclusionsThis study highlights the benefits of RT on various health parameters among NAFLD patients. While adding VES to RT resulted in greater decreases in aminotransferases, it did not provide further improvements in other variables. Additionally, enhancements in body composition, lipid profile, and glycemic control indices were possibly associated with decreased levels of CTRPs.Trial registrationRegistered retrospectively in the Iranian Registry of Clinical Trials (IRCT20220601055056N1) on December 21, 2023. Access at https://irct.behdasht.gov.ir/trial/69231.

Beneficial effect of oral semaglutide for type 2 diabetes mellitus in patients with metabolic dysfunction-associated steatotic liver disease: A prospective, multicentre, observational study.

To evaluate the efficacy and safety of oral semaglutide for type 2 diabetes mellitus (T2DM) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This was a single-arm, multicentre, prospective study. Among 80 consecutive patients with MASLD and T2DM who newly received oral semaglutide, 70 completed 48-week oral semaglutide treatment as scheduled and were included in an efficacy analysis. Dose adjustments of oral semaglutide were determined by each physician while monitoring efficacy and adverse events. Significant improvements in body weight, liver enzymes, lipid profile, and glycaemic control were found at 48 weeks compared with baseline values (all p < 0.01). Controlled attenuation parameter values significantly decreased from baseline to 48 weeks (p < 0.01). Changes in alanine aminotransferase concentrations (r = 0.37, p < 0.01) and controlled attenuation parameter values (r = 0.44, p < 0.01) were significantly correlated with changes in body weight. Liver fibrosis markers, such as type IV collagen 7S, Wisteria floribunda agglutinin-positive Mac-2-binding protein, fibrosis-4 index, and liver stiffness measurement, significantly decreased from baseline to 48 weeks (all p < 0.01). The most common adverse events were Grades 1-2 transient gastrointestinal symptoms, such as nausea (23 patients, 28.8%), dyspepsia (12, 15.0%) and appetite loss (4, 5.0%). Oral semaglutide treatment for T2DM in patients with MASLD leads to an improvement in liver steatosis and injury, surrogate markers of fibrosis, diabetic status, and lipid profile, and reduces body weight.