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In the past 2–3 decades, numerous attempts have been made to create an insulin‐secreting β cell line that maintains normal insulin secretion. However, primary β cell cultures have finite life and, therefore, cannot be used for long‐term experiments. The most widely used insulin‐secreting cell lines are Insulinoma‐1, rat insulinoma cell line, hamster pancreatic β cell line, mouse insulinoma, and β tumor cell line. Insulinoma‐derived cell lines show infinite growth in tissue culture but exhibit varying differences in their insulin responsiveness to glucose levels compared to normal β cells. Despite difficulties with β cell cultures, these cell lines have offered some useful insights in diabetes research concerning physiological functions and pathological investigations. In this review, we describe insulinoma cell lines used for drug screening, insulin secretion, cell viability, proliferation, and other relevant cellular functions. In addition, we have also incorporated recently developed human β cell lines. These cell lines have provided some helpful insights into physiological activities and pathology in diabetes research, despite challenges with β cell culturing. We propose that these cell lines could also be explored for screening Ayurvedic Rasayanas and homeopathy preparations for their cytotoxicity and insulin secretagogue activities to have evidence‐based data on alternative and complementary medicines. The easy availability of insulinoma and human β cell lines has facilitated diabetes research in understanding mechanism of action and cytotoxicity of drugs. This review summarizes the applications of existing insulinoma cell lines of rodent origin and newly developed human β cell lines. We highlight the importance of these in examining the cytotoxicity and insulin secretagogue activities of various drugs. Further, we propose that these cell lines could be used as a screening tool for Ayurvedic Rasayanas and homeopathy preparations. [ABSTRACT FROM AUTHOR]

Diabetes is a substantial public health issue, while its prevalence continues to rise worldwide, affecting millions of persons between the ages of 20 and 80, the development of new therapeutic classes improving glycemic control and consequently micro and macrovascular complications are needed. Today, diabetes treatment is daily for life, and should not be interrupted. However, insulin secretagogues medications, and exogenous self-administration of insulin provide efficient antidiabetic effects, but their misuse leads to hypoglycemic complications besides other risks, hence the need to look for other natural products not to use solely but in concert with others types of medications. In this review, we will highlight briefly the pathophysiology of diabetes and its complications, then we will report the main bioactive macromolecules derived from various sources of natural products providing anti-diabetic properties. However, further researches need to be carried out to face the limitations hampering the development of effective natural drugs for diabetes treatment. [Display omitted] • An overview of the pathophysiology of diabetes mellitus. • The potential of macromolecules derived from natural ressources for diabetes treatment. • Mechanisms of action of some natural products. • Limitations of current diabetes therapies with future perspectives to reduce undesirable side effects. [ABSTRACT FROM AUTHOR]

Background: The simplest form of carbohydrate that the human body can utilize efficiently to fuel various functions in our body is glucose. The food that is consumed by us in any form is acted upon by pancreatic juices, bile, and several other digestive enzymes and is converted into its simplest form, which is absorbed by the small intestine and is diffused into the circulatory system; from there, it is transported to other organs via GLUT-2 and GLUT-4 transporters. This process is very important, and so are the hormones involved in it. One such major hormone responsible for glucose homeostasis in the body is insulin. Its malfunction or that of either of its signaling components leads to a metabolic disorder termed "diabetes." Hyperglycemia is a grave condition associated with this complex disease and is of global concern. The impact of this disease can be life threatening if adequate precaution, medication, and therapy are overlooked. A plethora of synthetic drugs are available in the market, and the main goals of these antidiabetic medicines are to improve insulin sensitivity and/or production as well as to lower blood glucose levels. In all cases, frequent use of antidiabetic medication causes several after-effects. Results: Numerous studies in this field demonstrate that antidiabetic phytomolecules are highly effective against diabetes patients and are almost completely without side effects. Almost all classes of phytomolecules have been thoroughly evaluated to develop the noble plant-based drug. Conclusion: The current review discusses diabetes, its classification and management, worldwide occurrence, and the most crucial class of antidiabetic phytomolecules, for example, alkaloids, and terpenenoids as well as the parent molecule responsible for the bioactivity, subclasses, their mechanisms of action, plant sources and part, their superiority over synthetic drug, and new advances in this area. [ABSTRACT FROM AUTHOR]

Background: For ages, botanical medicine has been used in the treatment of diabetes mellitus (DM). Notoginsenoside R1 (NGR1), a Panax notoginseng (Burkill) F.H.Chen metabolite, has been documented to possess antidiabetic action in vivo. However, its precise molecular mechanism of action is not clear. Objectives: We evaluated NGR1's effects on blood glucose in vivo and then evaluated in vitro whether NGR1 has effects on insulin secretion and the probable molecular pathways involved in NGR1-induced insulin secretion. Methods: Diabetes was induced in mice by streptozotocin. Glucose tolerance test was performed before and after NGR1 was administered intraperitoneally to diabetic animals for 4 weeks. Static and perifusion experiments were performed using isolated female BALB/c mouse islets. Preproinsulin (Ins) mRNA expression was measured using q-PCR. Protein expression of PI3K/Akt pathway was assessed using the fully automated Wes™ capillary-based protein electrophoresis. Results: Treatment of diabetic mice with NGR1 improved their glucose intolerance. In vitro , NGR1 increased insulin secretion in a concentration-dependent manner. NGR1 initiated the secretion of insulin at 2 mM glucose and augmented glucose-stimulated insulin secretion which was sustained throughout NGR1 perifusion. NGR1-induced insulin secretion was not altered by a voltage gated calcium channel blocker or protein kinase A inhibitor. NGR1 did not significantly modulate Ins mRNA expression. However, NGR1 significantly increased the levels of phospho-Akt and phopho-p-85. Conclusion: In conclusion, this study has shown that NGR1 ameliorates hyperglycemia in diabetic mice. NGR1 has a direct insulin secretagogue activity on mouse islets, stimulates insulin secretion at both basal and postprandial glucose concentrations, and activates PI3K/Akt pathway to induce insulin secretion. These results suggest that NGR1 may provide an alternative therapy to manage DM. [ABSTRACT FROM AUTHOR]

Transient neonatal diabetes mellitus (TNDM) due to 6q duplication usually presents in the first 4 months of life, resolves before 18 months of life, and recurs in adolescence or adulthood. Insulin is the first-line treatment for chromosome 6–related neonatal diabetes in infancy. While there is no ideal treatment for patients with relapsed TNDM, residual β-cell function after remission of neonatal diabetes indicates a potential role for insulin secretagogues. Patients with 6q24 duplication have been successfully transitioned from insulin to sulfonylureas (SUs) in adolescence. We present the first report to our knowledge of TNDM secondary to a rare 6q23.3 duplication for which reemergence of diabetes was successfully transitioned from insulin to SU treatment. The successful transition to SU improved glycemic control, cost-effectiveness, and overall quality of life, while decreasing occurrence of hypoglycemia. [ABSTRACT FROM AUTHOR]

The leaves of Annona squamosa (AS) are known for their anti-diabetic properties, although the specific active principles and mechanisms of action remain unidentified. To explore these properties further, various extracts of AS leaves were prepared, including hexane, chloroform, butanol, hexane-washed methanol, total methanol extract, and water decoction. These extracts were characterized and tested for their inhibitory effects on pancreatic á-amylase activity under both in vitro and in vivo conditions. Among the extracts, the hexane extract demonstrated the lowest IC50 value of 0.925 mg/mL, prompting further investigation in a streptozotocin-induced diabetic model. The hypoglycemic response of this extract was correlated with its inhibitory activity against a-amylase in pancreatic homogenates. Different doses of the hexane extract were administered and compared with standard drugs such as acarbose and glimepiride. The results indicated that the hexane extract significantly reduced elevated glucose levels by 41.18±2.46% at a dosage of 100 mg/kg body weight (BW) and by 78.10±1.57% at 400 mg/kg BW. Additionally, it increased serum insulin levels from 8.56±1.42 µU/mL (in the experimental control group) to 16.26±1.20 µU/mL at the higher dosage of 400 mg/kg BW. The extract also inhibited á-amylase activity by 76.69±2.52% at 100 mg/kg BW and by 86.67±2.30% at 400 mg/kg BW. In comparison, glimepiride-treated rats exhibited a significant increase in serum insulin levels without a corresponding inhibition of a-amylase activity. Conversely, acarbose-treated rats showed significant inhibition of a-amylase but did not experience a notable rise in serum insulin levels. These findings suggest that the hexane extract of Annona squamosa leaves acts as both an insulin secretagogue--enhancing insulin secretion--and an inhibitor of pancreatic a-amylase in the small intestine. Consequently, this extract could be beneficial for managing postprandial hyperglycemia in diabetic patients. [ABSTRACT FROM AUTHOR]

Background: In 2019, coronavirus disease 2019 (COVID-19) emerged in China, spreading globally with significant impacts in Japan, including the Delta and Omicron variants. The research identified risk factors such as age, chronic diseases, and lifestyle choices, emphasizing the need for further study on the association between underlying health conditions, treatments, and COVID-19 severity in Japan. Methods: This study used a nationwide medical database to analyze the association between COVID-19 underlying conditions and pharmacological interventions to identify risk factors for disease severity. We examined the Japanese COVID-19 dataset from Medical Data Vision, selecting patients diagnosed with COVID-19 between January 2020 and December 2022. Logistic regression was used to calculate the odds ratios (ORs) for intensive care unit treatment- or ventilator use-related risk factors. Results: Among 650,317 patients (mean age: 52.1 ± 20.9 years; male individuals: 324,127; female individuals: 326,190), factors that significantly increased the severe disease risk (OR [95% confidence interval]) included age > 65 years (1.31 [1.27–1.36]), hypertension (1.34 [1.28–1.41]), cardiovascular disease (1.74 [1.67–1.81]), and use of beta-blockers (2.09 [2.00–2.17]), calcium blockers (1.97 [1.89–2.06]), angiotensin-converting enzyme inhibitors (1.41 [1.33–1.49]), low-dose aspirin (1.38 [1.32–1.45]), and insulin (7.14 [6.87–7.43]). Conversely, factors that reduced the severe disease risk included female sex and the use of sulfonylureas, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide-1 receptor agonists, and alpha-glucosidase inhibitors. Conclusions: Patients using cardiovascular medications faced a higher risk, whereas those receiving diabetes treatment had a lower risk. Appropriate pharmacotherapy and risk factor identification can aid in the prevention of severe COVID-19. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionsTo compare the efficacy and safety of insulin degludec biosimilar B01411 (HS-IDeg) with originator insulin degludec-Tresiba (NN-IDeg) in Chinese patients with type 2 diabetes mellitus (T2DM) who were inadequately controlled on oral antidiabetic drugs (OADs) for at least 3 months.This multicenter, randomized, open-label, parallel-group, active-controlled, phase 3 study enrolled 362 participants with T2DM. Participants were stratified according to whether the insulin secretagogue (sulfonylurea or glinide) had been used before the screening and then randomized 1:1 to receive once-daily subcutaneous injections of HS-IDeg (n = 180) or NN-IDeg (n = 182) for 18 weeks. The primary endpoint was the change from baseline in glycated hemoglobin (HbA1c) to week 18.At week 18, the least squares (LS) mean change in HbA1c from baseline was −1.34% (95% CI −1.47 to −1.21) and −1.25% (95% CI −1.38 to −1.12) with HS-IDeg and NN-IDeg, respectively. The LS mean difference (HS-IDeg minus NN-IDeg) in HbA1c at week 18 was −0.09% (95% CI −0.28 to 0.10), demonstrating non-inferiority of HS-IDeg to NN-IDeg. Participants achieving HbA1c <7.0% at week 18 were 34.5% and 29.5% with HS-IDeg and NN-IDeg, respectively. Mean decreases in fasting plasma glucose and standard deviation of blood glucose were similar between both groups. Safety and tolerability, including hypoglycemia, adverse events, and weight change were similar between both groups. No severe hypoglycemia and no death occurred in the study.HS-IDeg and NN-IDeg demonstrated similar efficacy and safety over 18 weeks of treatment in Chinese patients with T2DM who had inadequate responses to OADs for at least 3 months. [ABSTRACT FROM AUTHOR]

Objective: Maturity onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY. Methods: MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated. Results: A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) HNF1A; 8 (3.6%) HNF4A, 8 (3.6%) KLF11 and 7 (3.1%) HNF1B. The remaining 12 variants were: PDX (n=1), NEUROD1 (n=3), CEL (n=1), INS (n=3), ABCC8 (n= 3) and KJNC11 (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral anti-diabetic treatment. Conclusion: This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the prevalence of inappropriate tight glycemic control in older adults with type 2 diabetes and other chronic conditions in New York City, and to identify factors associated with this practice. Methods: We conducted a retrospective cohort study using the INSIGHT Clinical Research Network. The study population included 11,728 and 15,196 older adults in New York City (age ≥ 75 years) with a diagnosis of type 2 diabetes, and at least one other chronic medical condition, in 2017 and 2022, respectively. The main outcome of interest was inappropriate tight glycemic control, defined as HbA1c <7.0% (<53 mmol/mol) with prescription of at least one high‐risk agent (insulin or insulin secretagogue). Results: The proportion of older adults with inappropriate tight glycemic control decreased by nearly 19% over a five‐year period (19.4% in 2017 to 15.8% in 2022). There was a significant decrease in insulin (27.8% in 2017; 24.3% in 2022) and sulfonylurea (29.4% in 2017; 21.7% in 2022) medication prescription, and increase in use of GLP‐1 agonists (1.8% in 2017; 11.4% in 2022) and SGLT‐2 inhibitors (5.8% in 2017; 25.1% in 2022), among the total population. Factors associated with inappropriate tight glycemic control in 2022 included history of heart failure (adjusted odds ratio [aOR] 1.38), chronic kidney disease ([aOR] 1.93), colorectal cancer ([aOR] 1.38), acute myocardial infarction ([aOR] 1.28), "other" ([aOR] 0.72) or "unknown" ([aOR] 0.72) race, and a point increase in BMI ([aOR] 0.98). Conclusions: We found an encouraging trend toward less use of high‐risk medication strategies for older adults with type 2 diabetes and multiple chronic conditions. However, one in six patients in 2022 still had inappropriate tight glycemic control, indicating a need for continued efforts to optimize diabetes management in this population. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 2-month-old boy diagnosed with diabetic ketoacidosis (DKA) and permanent neonatal diabetes mellitus (PNDM) due to a mutation in the KCNJ11 gene. Topics discussed include the clinical presentation of neonatal diabetes that can mimic sepsis, the importance of genetic testing for proper diagnosis and management, and the treatment approach, which involved insulin therapy followed by oral sulfonylurea.

Background: Oral semaglutide in older subjects with type 2 diabetes was as effective as in younger subjects, according to phase 3 clinical trials. However, its efficacy can be limited in very aged population, due to the presence of impaired cognitive function and the complex instructions for its use. Here, we investigated its efficacy and safety by further age bracket in older subjects in real-world. Methods: We retrospectively studied subjects > 65 years of age with type 2 diabetes who started oral semaglutide treatment. The primary outcome was the change in glycated hemoglobin (HbA1c) over 6 months. Adverse events and cognitive function were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) and the Hasegawa Dementia Rating Scale-revised (HDS-R). The achievement rate of glycemic targets was evaluated based on the age, health status of subjects and their use of anti-diabetic agents which can cause hypoglycemia, with additional analysis between two subgroups; early (65–74) versus late (≥ 75) older. Furthermore, we evaluated the relationships between their improvements in HbA1c and the baseline characteristics of the subjects, including their cognitive function and insulin secretory capacity. Results: We studied the efficacy of the drug in 24 subjects. Their HbA1c and body weight significantly decreased (− 13.1 ± 7.5 mmol/mol and − 3.0 ± 2.4 kg, respectively; P < 0.01). Although cognitive function was lower in the late older group (r = −0.57, P < 0.01), changes in HbA1c showed no difference between the two subgroups (P = 0.66) and it correlated with the insulin secretory capacity rather than cognitive function (r = −0.49, P < 0.05). Glycemic targets were more likely to be achieved (P < 0.01), but HbA1c excessively decreased in late older subjects who were also using insulin or an insulin secretagogue. The frequency of adverse events was similar to that in the clinical trial, whereas discontinuation of medication were more frequent among the late older subjects (Early; n = 2, Late; n = 4). Conclusions: Oral semaglutide improves the glycemic control of older subjects, but it might be a risk for potential hypoglycemia and discontinuation because of adverse events in subjects of ≥ 75 years. Attention should be paid to insulin secretory capacity and concomitant medications rather than concern about adherence. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is associated with an increased risk of fractures due to deterioration of bone quality, which can be referred to as "diabetic osteodystrophy." Furthermore, the risk of fracture is increased in DM, even if bone mineral density is normal or high and is associated with increased morbidity if a fracture develops. In addition to the pathophysiological mechanisms of DM, diabetesrelated complications and drugs used in the treatment of DM may also affect bone health. Moreover, the increased risk of falling due to microvascular complications, hypoglycemia, and postural hypotension also contributes to the development of fractures. Individuals with DM should be screened for osteoporosis with recommendations similar to those of the general population. When diagnosing osteoporosis and deciding on treatment, it should be kept in mind that DM may be an important risk factor, and lower threshold values of the T score should be used. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) significantly increases the risk of cardiovascular diseases. Despite advances in glycemic control, managing cardiovascular risk remains a critical challenge. This systematic review aims to assess and compare the cardiovascular outcomes associated with three classes of antidiabetic medications: sulfonylureas, Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with T2DM. A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases, including PubMed, Embase, Cochrane Library, and Google Scholar, were searched for relevant studies published between 2019 and 2023. Inclusion criteria were adults (=18 years) with T2DM, studies assessing cardiovascular outcomes with the specified medications, randomized controlled trials, observational studies, or meta-analyses. Two independent reviewers performed data extraction and risk of bias assessments. From the initial 1,543 records, 12 studies were included involving 61,534 patients. As a result, GLP-1 RAs demonstrated favorable cardiovascular safety and efficacy, particularly in reducing major adverse cardiovascular events and all-cause mortality. DPP-4 inhibitors were associated with neutral cardiovascular outcomes but indicated an elevated risk of cardiac failure in some studies. In recent studies, sulfonylureas, previously associated with cardiovascular concerns, showed no consistent evidence of increased cardiovascular risk. These findings highlight the importance of personalized treatment strategies to optimize cardiovascular outcomes in patients with T2DM. [ABSTRACT FROM AUTHOR]

Hypoglycemic medications that could be coadministered with prebiotics and functional foods can potentially reduce the burden of metabolic diseases such as Type 2 Diabetes Mellitus (T2DM). The efficacy of drugs such as metformin and sulfonylureas can be enhanced by the activity of the intestinal microbiome elaborated metabolites. Functional foods such as prebiotics (e.g., oligofruc tose) and dietary fibers can treat a dysbiotic gut microbiome by enhancing the diversity of microbial niches in the gut. These beneficial shifts in intestinal microbiome profiles include an increased abundance of bacteria such as Faecalibacterium prauznitzii, Akkermancia muciniphila, Roseburia species, and Bifidobacterium species. An important net effect is an increase in the levels of luminal SCFAs (e.g., butyrate) that provide energy carbon sources for the intestinal microbiome in crossfeeding activities, with concomitant improvement in intestinal dysbiosis with attenuation of inflammatory sequalae and improved intestinal gut barrier integrity, which alleviates the morbidity of T2DM. Oligosaccharides administered adjunctively with pharmacotherapy to ameliorate T2DM represent current plausible treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Older adults with diabetes mellitus require drug treatment considering their frailty, cognitive function, and hypoglycemia. Objective: We investigated the association between diabetic pharmacologic therapy and both diabetic complications and frailty across eight diabetes-specific outpatient clinics nationwide. Methods: Participants (aged 60–80 years) who had type 2 diabetes and did not require nursing care were included in the study. Basic attributes, patient background, complications, hypoglycemic status, body weight, body composition, blood tests, grip strength, and Kihon Checklist (a frailty index) and self-care scores were obtained. Descriptive statistics, t-test, chi-square test, and regression analyses were employed for evaluation. Results: Overall, 417 participants were included (224 men, 193 women, mean age 70.1 ± 5.4 years, diabetes duration 14.9 ± 10.9 years, body mass index 24.5 ± 3.8, glycated hemoglobin 7.22 ± 0.98%, proportion of individuals with frailty and prefrailty, 19.9% and 41.0%, respectively). All drugs were used more frequently in prefrailty conditions. Each diabetes medication was related to complications, body composition, and frailty, as follows: sulfonylurea (lower hypoglycemia); glinide (severe hypoglycemia, retinopathy, weaker grip strength, high Kihon Checklist score, decreased physical activities); alpha-glucosidase inhibitors (no association); biguanide (high body mass index, high body fat, stronger grip strength); thiazolidinedione (decreased instrumental activities of daily living); dipeptidyl‐peptidase‐4 inhibitors (no association); sodium-glucose cotransporter 2 inhibitors; retinopathy, high body mass index and Kihon Checklist score, and depressive mood); glucagon-like peptide-1 receptor agonists (high body mass index and body fat and poor nutritional status); and insulin preparations (hypoglycemia, retinopathy, neuropathy, nephropathy, cardiovascular diseases, weaker grip strength, and high Kihon Checklist score and physical inactivity). Conclusions: Some formulations, such as glinide, sodium-glucose cotransporter 2 inhibitors, and insulin, are associated with an increased frequency of frailty, warranting careful and individualized diabetes treatment. [ABSTRACT FROM AUTHOR]

This review evaluates the current evidence on the safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with type 2 diabetes mellitus (T2DM) fasting during Ramadan. All studies included in the review were conducted in Asia and the Middle East. Overall, the evidence suggests that SGLT2 inhibitors are a safe and effective treatment option for most T2DM patients fasting during Ramadan. The average incidence of symptomatic hypoglycemia is 12.5%, but ranges from 0.7% to 27%, depending on the study population and concomitant use of other medications. The risk of hypoglycemia is increased when SGLT2 inhibitors are used in combination with insulin and/or sulfonylureas. Therefore, patients taking SGLT2 inhibitors in combination with insulin and/or sulfonylureas can take steps to mitigate this risk, such as having their insulin and/or sulfonylurea doses adjusted and being closely monitored for hypoglycemia. Patients taking SGLT2 inhibitors may be at increased risk of dehydration. To mitigate the risk of dehydration, patients should be advised to consume adequate fluids during the fast-breaking hours. Further research is warranted to validate these findings and extend their applicability to high-risk populations and other regions of the world. Plain Language Summary: Safety and effectiveness of sodium-glucose co-transporter 2 inhibitors on glycemic control in patients with type 2 diabetes mellitus fasting during Ramadan: a review This review delves into the existing evidence regarding the safety and efficacy of sodium-glucose co-transporter 2 (SGLT2) inhibitors for patients with type 2 diabetes mellitus (T2DM) who observe Ramadan fasting. The studies reviewed were conducted exclusively in Asia and the Middle East. Overall, the gathered evidence suggests that SGLT2 inhibitors constitute a safe and effective treatment option for most T2DM patients fasting during Ramadan. While a slightly elevated risk of dehydration compared to other medications may exist, this is generally well-tolerated. To mitigate the risk of dehydration, patients should be advised to consume adequate fluids during the fast-breaking hours. However, further research is warranted to validate these findings and extend their applicability to high-risk populations and other world regions. [ABSTRACT FROM AUTHOR]

Background: Achieving good glycaemic control is essential to reducing the risk of diabetes complications. Insulin is the most effective therapy for achieving good glycaemic control; however, it is associated with a higher risk of hypoglycaemia, especially with human insulin. This study aimed to evaluate the efficacy of intensification from human to analogue insulin and its added cost. Methods: This retrospective study was conducted at the Hospital Universiti Sains Malaysia (HUSM). Patients with type 2 diabetes mellitus (T2DM) who underwent intensification for at least 3 months from human to analogue insulin were included in this study. The patients' medical records, haemoglobin A1c (Hba1c) and fasting blood sugar (FBS) were retrieved. The total cost pre- and post-intensification of insulin was obtained from the pharmacy database. Differences in HbA1c, FBS and total insulin cost pre- and post-intensification were analysed. Results: A total of 163 patients with T2DM who had intensification from human to analogue insulin were included in this study. HbA1c and FBS levels were significantly lower in analogue insulin. However, the differences were not clinically significant, as the mean reduction in HbA1c was less than 0.5%. Meanwhile, the total costs of analogue insulin for 3 months were higher. Conclusion: There were no clinically significant improvements in patients' HbA1c and FBS after the intensification of insulin, despite the extra costs spent. Hence, it is vital to choose the right group of patients to receive an insulin analogue to maximise its benefit but at the most optimal cost. [ABSTRACT FROM AUTHOR]

Since diabetes and its complications have been thought to exaggerate cardiorenal disease, resulting in a short lifespan, we investigated causes of death and lifespans in individuals with and without diabetes at a Japanese community general hospital during the period from 2011 to 2020. Causes of death and age of death in individuals with and those without diabetes were compared, and associations between medications used and age of death were statistically analyzed. A total of 2326 deaths were recorded during the 10-year period. There was no significant difference between the mean ages of death in individuals with and those without diabetes. Diabetic individuals had higher rates of hepato-pancreatic cancer and cardio-renal failure as causes of death. The prescription rates of antihypertensives, antiplatelets, and statins in diabetic individuals were larger than those in non-diabetic individuals. Furthermore, the use of sulfonyl urea or glinides and insulin was independently and inversely associated with the age of death. In conclusion, individuals with diabetes were treated with comprehensive pharmaceutical interventions and had life spans comparable to those of individuals without diabetes. This study's discovery of an inverse relationship between the use of insulin secretagogues or insulin and the age of death suggests that the prevention of life-threatening hypoglycemia is crucial for individuals with diabetes. [ABSTRACT FROM AUTHOR]

There are now an estimated five million people living with diabetes in the UK, most have type 2 diabetes. The COVID-19 pandemic affected access to care, led to delays in diagnoses of diabetes and many people with diabetes experienced a deterioration in their diabetes control. This article provides guidance on how nurses can work with people at risk of diabetes to prevent diabetes, to induce remission and how to use medication to treat diabetes. [ABSTRACT FROM AUTHOR]

A 74-year-old patient with type 2 diabetes mellitus received basal-bolus insulin, insulin secretagogues, and sodium glucose transporter 2 (SGLT2) inhibitors. After immune checkpoint inhibitor treatment for lung cancer, he suffered from depressed consciousness with a urinary ketone body (3+). When all hypoglycemic treatments were discontinued, his serum blood glucose remained at 121 mg/dL. He was diagnosed with euglycemic diabetic ketosis. Endocrine loading tests revealed isolated adrenocorticotropic hormone (ACTH) deficiency as an immune-related adverse event. It was suggested that euglycemic diabetic ketosis was induced by the self-suspension of insulin and insulin secretagogues, adrenal insufficiency, SGLT2 inhibitors, and carbohydrate intake shortage. [ABSTRACT FROM AUTHOR]

With the deepening of aging in China, the prevalence of diabetes in older people has increased noticeably, and standardized diabetes management is critical for improving clinical outcomes of diabetes in older people. In 2021, the National Center of Gerontology, Chinese Society of Geriatrics, and Diabetes Professional Committee of Chinese Aging Well Association organized experts to write the first guideline for diabetes diagnosis and treatment in older people in China, the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2021 Edition). The guideline emphasizes that older patients with diabetes are a highly heterogeneous group requiring comprehensive assessment and stratified and individualized management strategies. The guideline proposes simple treatments and de‐intensified treatment strategies for older patients with diabetes. This edition of the guideline provides clinicians with practical and operable clinical guidance, thus greatly contributing to the comprehensive and full‐cycle standardized management of older patients with diabetes in China and promoting the extensive development of clinical and basic research on diabetes in older people and related fields. In the past 3 years, evidence‐based medicine for older patients with diabetes and related fields has further advanced, and new treatment concepts, drugs, and technologies have been developed. The guideline editorial committee promptly updated the first edition of the guideline and compiled the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition). More precise management paths for older patients with diabetes are proposed, for achieving continued standardization of the management of older Chinese patients with diabetes and improving their clinical outcomes. [ABSTRACT FROM AUTHOR]

Stem cell-derived islets (SC-islets) are not only an unlimited source for cell-based therapy of type 1 diabetes but have also emerged as an attractive material for modeling diabetes and conducting screening for treatment options. Prior to SC-islets becoming the established standard for disease modeling and drug development, it is essential to understand their response to various nutrient sources in vitro. This study demonstrates an enhanced efficiency of pancreatic endocrine cell differentiation through the incorporation of WNT signaling inhibition following the definitive endoderm stage. We have identified a tri-hormonal cell population within SC-islets, which undergoes reduction concurrent with the emergence of elevated numbers of glucagon-positive cells during extended in vitro culture. Over a 6-week period of in vitro culture, the SC-islets consistently demonstrated robust insulin secretion in response to glucose stimulation. Moreover, they manifested diverse reactivity patterns when exposed to distinct nutrient sources and exhibited deviant glycolytic metabolic characteristics in comparison to human primary islets. Although the SC-islets demonstrated an aberrant glucose metabolism trafficking, the evaluation of a potential antidiabetic drug, pyruvate kinase agonist known as TEPP46, significantly improved in vitro insulin secretion of SC-islets. Overall, this study provided cell identity dynamics investigation of SC-islets during prolonged culturing in vitro, and insights into insulin secretagogues. Associated advantages and limitations were discussed when employing SC-islets for disease modeling.

This editorial comments on the article by Haider et al. [ABSTRACT FROM AUTHOR]

The article focuses on the limitations of using A1C as a diagnostic and monitoring tool for diabetes, highlighting cases of misdiagnosis due to analytical interference. Topics include the impact of conditions affecting erythrocyte turnover on A1C, potential interference with hemoglobin variants, and the importance of critically interpreting A1C results.

The search for solid solutions of class-two insulin secretagogues, tolbutamide and chlorpropamide, reveals a rare case of monotropic polymorphism for the mixed crystals. At any stoichiometry, two crystal forms are isolated that are kinetically stable at room temperature from a few months to over a year. Dissolution tests certify the solubility advantage of the solid solutions over the pure drugs as well as their physical mixture, suggesting a potential application as a highly soluble co-drug formulation. [ABSTRACT FROM AUTHOR]

Background: For older adults with type 2 diabetes (T2D) treated with insulin or sulfonylureas, Endocrine Society guideline recommends HbA1c between 7% to <7.5% for those in good health, 7.5% to <8% for those in intermediate health, and 8% to <8.5% for those in poor health. Our aim was to examine associations between attained HbA1c below, within (reference), or above recommended target range and risk of complication or mortality. Methods: Retrospective cohort study of adults ≥65 years old with T2D treated with insulin or sulfonylureas from an integrated healthcare delivery system. Cox proportional hazards models of complications during 2019 were adjusted for sociodemographic and clinical variables. Primary outcome was a combined outcome of any microvascular or macrovascular event, severe hypoglycemia, or mortality during 12‐month follow‐up. Results: Among 63,429 patients (mean age: 74.2 years, 46.8% women), 8773 (13.8%) experienced a complication. Complication risk was significantly elevated for patients in good health (n = 16,895) whose HbA1c was above (HR 1.97, 95% CI 1.62–2.41) or below (HR 1.29, 95% CI 1.02–1.63) compared to within recommended range. Among those in intermediate health (n = 30,129), complication risk was increased for those whose HbA1c was above (HR 1.45, 95% CI 1.30–1.60) but not those below the recommended range (HR 0.99, 95% CI 0.89–1.09). Among those in poor health (n = 16,405), complication risk was not significantly different for those whose HbA1c was below (HR 0.98, 95% CI 0.89–1.09) or above (HR 0.96, 95% CI 0.88–1.06) recommended range. Conclusions: For older adults with T2D in good health, HbA1c below or above the recommended range was associated with significantly elevated complication risk. However, for those in poor health, achieving specific HbA1c levels may not be helpful in reducing the risk of complications. See related editorial by Green and Lee in this issue. [ABSTRACT FROM AUTHOR]

We previously developed, synthesized and tested light‐activated sulfonylureas for optical control of KATP channels and pancreatic beta cell activity in vitro and in vivo. Such technology relies on installation of azobenzene photoswitches onto the sulfonylurea backbone, affording light‐dependent isomerization, alteration in ligand affinity for SUR1 and hence KATP channel conductance. Inspired by molecular dynamics simulations and to further improve photoswitching characteristics, we set out to develop a novel push‐pull closed ring azobenzene unit, before installing this on the sulfonylurea glimepiride as a small molecule recipient. Three fine‐tuned, light‐activated sulfonylureas were synthesized, encompassing azetidine, pyrrolidine and piperidine closed rings. Azetidine‐, pyrrolidine‐ and piperidine‐based sulfonylureas all increased beta cell Ca2+‐spiking activity upon continuous blue light illumination, similarly to first generation JB253. Notably, the pyrrolidine‐based sulfonylurea showed superior switch OFF performance to JB253. As such, third generation sulfonylureas afford more precise optical control over primary pancreatic beta cells, and showcase the potential of pyrrolidine‐azobenzenes as chemical photoswitches across drug classes. [ABSTRACT FROM AUTHOR]

During the last decade, the landscape of type 2 diabetes (T2D) management has been completely transformed, moving from a glucose-centric perspective to a holistic approach that also takes into account weight control and organ protection. Dipeptidyl peptidase-4 inhibitors (DPP4i) are oral agents that have been used for the treatment of T2D for almost 20 years. Although they present an excellent safety profile, including the risk of hypoglycemia, they lack the spectacular cardiorenal benefits and weight-loss effects of the newer antidiabetic agents. This poses the question of whether they still deserve a place in the arsenal of drugs against T2D. In this article, we use a hypothetical case scenario to illustrate possible patient profiles where DPP4i could prove useful in the clinical setting. We discuss the advantages and disadvantages of the category, focusing on glycemic control, weight management, and cardiorenal protection, which are the pillars of modern T2D management, also considering its safety profile and cost-effectiveness. We conclude that in most cases, DPP4i present a more favorable risk–benefit ratio compared to sulfonylureas, which are still widely prescribed throughout the world. We also suggest that future research should clarify the reasons behind the contradictory findings between human and animal studies on cardiorenal effects of the class and identify subgroups of patients who would derive most benefit with DPP4i treatment. [ABSTRACT FROM AUTHOR]

The article comments on a study which showed that people who may benefit the most from treatment deintensification are less likely to be willing to take less type 2 diabetes medication. Topics covered include the dependence of willingness on the type of medication like insulin or sulfonylurea, the uncertainty of most older patients in reducing the dose of one or more of their medicines, and medication issues via patient-provider interaction.

See the Reply by Lee et al. in this issue. [ABSTRACT FROM AUTHOR]

Background: Sulfonylureas are oral glucose‐lowering medications positioned as a second‐line therapy for type 2 diabetes. Evidence relating them to cognitive decline has been mixed. The objective was to determine whether sulfonylurea use was associated with a differential risk of dementia compared with dipeptidyl peptidase‐4 (DPP4) inhibitor use. Methods: Using administrative data from residents in Ontario, Canada, adults aged ≥66 years who were new users of a sulfonylurea or a DPP4 inhibitor from June 14, 2011, to March 31, 2021 entered this population‐based retrospective cohort study. Dementia was ascertained using a validated algorithm for Alzheimer's disease and related dementias. Propensity‐score weighted Cox proportional hazards models were used to obtain adjusted hazard ratios (aHR) and confidence intervals (CI) for time to incident dementia. The observation window started at 1 year after cohort entry to mitigate protopathic bias due to delayed diagnosis. The primary analysis used an intention‐to‐treat exposure definition. A separate propensity‐score weighted analysis was conducted to explore within‐class differences in dementia risk among sulfonylurea new users selected from the primary cohort. Results: Among 107,806 DPP4 inhibitor new users and 37,030 sulfonylurea new users, sulfonylureas compared with DPP4 inhibitors were associated with a higher risk of dementia (18.4/1000 person‐years; aHR [95% CI] = 1.09 [1.04–1.15]) over a mean follow‐up of 4.82 years from cohort entry. Glyburide compared to gliclazide exhibited a higher dementia risk (aHR [95% CI] = 1.17 [1.03–1.32]). Conclusion: New use of a sulfonylurea especially glyburide was associated with a higher dementia risk compared with new use of a DPP4 inhibitor in older adults with diabetes. See related Editorial by Lee et al. in this issue. [ABSTRACT FROM AUTHOR]

Primary care NPs are central to the management of diabetes mellitus, which carries with it the risk of hypoglycemia. Fully understanding risk factors, prevention strategies, and treatment assist in reducing hypoglycemic events. This article details hypoglycemia, risk factors for hypoglycemia, prevention strategies, and appropriate treatment plans. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes (T2D) is a well‐recognised cardiovascular disease (CVD) risk factor, and recent guidelines for the management of T2D include consideration of CVD risk. Aim: To assess whether contemporary clinical management of Australians with T2D is in accord with recent national and international guidelines. Methods: This Australia‐specific analysis of the CAPTURE study, a non‐interventional, cross‐sectional study included adults diagnosed with T2D ≥180 days prior to providing informed consent and visiting primary or specialist care. Main outcome measures were the use of blood glucose‐lowering medications (BGLMs), BGLMs with proven cardiovascular benefits and other CVD medications, stratified by CVD status and care setting. Results: Of 824 Australian participants in the CAPTURE sample, 332 (40.3%) had CVD. Oral BGLMs were used by 83.9% of all participants, most commonly metformin (76.0%), dipeptidyl peptidase‐4 inhibitors (28.8%), sodium‐glucose cotransporter‐2 inhibitors (SGLT2is; 21.8%) and sulfonylureas (21.7%). Insulin was used by 29.2% of participants. BGLMs with proven CV benefit were used by 22.6%; glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) were less commonly used than SGLT2is in all CVD groups, but these drug classes were more often prescribed in specialist than primary care (SGLT2is 25.4 vs 20.7%, GLP‐1 RAs 3.2 vs 0.8% respectively). Use of non‐BGLMs for CVD risk reduction appeared consistent with guidelines. Conclusions: Use of BGLMs with CVD benefits appears low in Australia, irrespective of CVD status. This likely reflects the delay in translation of clinical evidence into contemporary care and prescribing restrictions. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes is more prevalent among Aboriginal and Torres Strait Islander Peoples, especially those living in rural than urban areas. However, little is known about how diabetes is managed in different settings. Objective: To investigate differences in the prevalence of diabetes and the prescription of antidiabetic medications for Aboriginal and/or Torres Strait Islander Peoples living in urban or rural Australia. Design: Cross‐sectional study using de‐identified electronic medical records of 29,429 Aboriginal and/or Torres Strait Islander adults (60.4% females; mean age 45.2 ± 17.3 years) regularly attending 528 'mainstream' Australian general practices (MedicineInsight) in 2018. Findings: The prevalence of diabetes was 16.0%, and it was more frequent among those living in rural areas (22.0; 95% CI 19.3–24.4) than inner regional (17.6%; 95% CI 16.0–19.2) or major cities (15.8%; 95% CI 14.7–17.0; p < 0.001). The highest prevalence of diabetes was for males living in rural settings (25.0%). Of those with diabetes, 71.6% (95% CI 69.0–74.0) were prescribed antidiabetics, with a similar frequency in urban and rural areas (p = 0.291). After adjustment for sociodemographics, the only difference in diabetes management was a higher prescription of sulfonylureas in rural areas than in major cities (OR 1.39; 1.07–1.80). Discussion: The prevalence of diabetes was similar to other national data, although we found it was more frequent amongst Aboriginal and/or Torres Strait Islander males, especially those from rural areas. Conclusion: Despite current recommendations, one‐in‐four Indigenous Australians with diabetes were not prescribed antidiabetics. The clinical significance of more frequent prescriptions of sulfonylureas in rural locations remains unclear. [ABSTRACT FROM AUTHOR]

Insulin therapy is indispensable for achieving glycemic control in all patients with type 1 diabetes mellitus and many patients with type 2 diabetes mellitus. Insulin injections are associated with negative connotations in patients owing to administration discomfort and adverse effects such as hypoglycemia and weight gain. Insulin administered orally can overcome these limitations by providing a convenient and effective mode of delivery with a potentially lower risk of hypoglycemia. Oral insulin mimics the physiologic process of insulin secretion, absorption into the portal circulation, and subsequent peripheral delivery, unlike the subcutaneous route that results in peripheral hyperinsulinemia. Insulin tregopil (IN-105), a new generation human recombinant insulin, methoxy (polyethylene glycol) hexanoyl human recombinant insulin, is developed by Biocon as an ultra-fast onset short-acting oral insulin analog. This recombinant oral insulin is a single short-chain amphiphilic oligomer modified with the covalent attachment of methoxy-triethylene-glycol-propionyl moiety at Lys-β29-amino group of the B-chain via an amide linkage. Sodium caprate, an excipient in the insulin tregopil formulation, is a permeation enhancer that increases its absorption through the gastrointestinal tract. Also, meal composition has been shown to non-significantly affect its absorption. Several global randomized, controlled clinical trials have been conducted in type 1 and type 2 diabetes patients towards the clinical development of insulin tregopil. The formulation shows post-prandial glucose control that is more effective than placebo throughout the meal period; however, compared with an active comparator insulin aspart, the post-prandial control is more effective mainly in the early post-meal period. It shows a good safety profile with a lower incidence of clinically significant hypoglycemia. This review covers the overall clinical development of insulin tregopil establishing it as an ultra-fast onset, short-acting oral insulin analog for optimizing post-prandial glucose. [ABSTRACT FROM AUTHOR]

Background: Sodium‐glucose cotransporter‐2 inhibitor (SGLT2I) use has increased among community‐dwelling populations, but little is known about how clinicians have prescribed them for US nursing home (NH) residents. We described the adoption of SGLT2Is by prescribers caring for long‐stay NH residents by clinician specialty and over time, compared with sulfonylureas, an older diabetes medication class. Methods: We conducted a retrospective cohort study of prescribers of SGLT2Is and sulfonylureas for all long‐stay US NH residents aged 65 years or older (2017–2019). Using 100% of Medicare Part D claims linked to prescriber characteristics data, we identified all dispensings of SGLT2Is and sulfonylureas for long‐stay NH residents and their associated prescribers. We described the distribution of prescriber specialties for each drug class over time as well as the number of NH residents prescribed SGLT2s versus sulfonylureas. We estimated the proportions of prescribers who prescribed both drug classes versus only sulfonylureas or only SGLT2Is. Results: We identified 36,427 unique prescribers (SGLT2I: N = 5811; sulfonylureas: N = 35,443) for 117,667 NH residents between 2017 and 2019. For both classes, family medicine and internal medicine physicians accounted for most prescriptions (75%–81%). Most clinicians (87%) prescribed only sulfonylureas, 2% prescribed SGLT2Is only, and 11% prescribed both. Geriatricians were least likely to prescribe only SGLT2Is. We observed an increase in the number of residents with SGLT2I use from n = 2344 in 2017 to n = 5748 in 2019. Conclusions: Among NH residents, most clinicians have not incorporated SGLT2Is into their prescribing for diabetes, but the extent of use is increasing. Family medicine and internal medicine physicians prescribed the majority of diabetes medications for NH residents, and geriatricians were the least likely to prescribe only SGLT2Is. Future research should explore provider concerns regarding SGLT2I prescribing, particularly adverse events. [ABSTRACT FROM AUTHOR]

Post-pancreatitis diabetes mellitus, pancreatic cancer-related diabetes, and cystic fibrosis-related diabetes are often underappreciated. As a result, a substantial proportion of people with these sub-types of diabetes receive antidiabetic medications that may be suboptimal, if not harmful, in the context of their underlying disease of the exocrine pancreas. The present article delineates both classical (biguanides, insulin, sulfonylureas, α-glucosidase inhibitors, thiazolidinediones, and meglitinides) and newer (glucagon-like peptide-1 receptor agonists, amylin analogs, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors, D2 receptor agonists, bile acid sequestrants, and dual glucagon-like peptide-1 receptor and glucose-dependent insulinotropic polypeptide receptor co-agonists) therapies and provides recommendations for managing people with diabetes of the exocrine pancreas based on the most up-to-date clinical evidence. Also, several emerging directions (lipid-enriched pathways, Y4 receptor agonism, glucagon-like peptide-1 and glucagon receptor co-agonism) are presented with a view to informing the process of new drug discovery and development. [ABSTRACT FROM AUTHOR]

Diabetes medications may modify the risk of certain cancers. We systematically searched MEDLINE, Embase, Web of Science, and Cochrane CENTRAL from 2011 to March 2021 for studies evaluating associations between diabetes medications and the risk of breast, lung, colorectal, prostate, liver, and pancreatic cancers. A total of 92 studies (3 randomized controlled trials, 64 cohort studies, and 25 case–control studies) were identified in the systematic review, involving 171 million participants. Inverse relationships with colorectal (n = 18; RR = 0.85; 95% CI = 0.78–0.92) and liver cancers (n = 10; RR = 0.55; 95% CI = 0.46–0.66) were observed in biguanide users. Thiazolidinediones were associated with lower risks of breast (n = 6; RR = 0.87; 95% CI = 0.80–0.95), lung (n = 6; RR = 0.77; 95% CI = 0.61–0.96) and liver (n = 8; RR = 0.83; 95% CI = 0.72–0.95) cancers. Insulins were negatively associated with breast (n = 15; RR = 0.90; 95% CI = 0.82–0.98) and prostate cancer risks (n = 7; RR = 0.74; 95% CI = 0.56–0.98). Positive associations were found between insulin secretagogues and pancreatic cancer (n = 5; RR = 1.26; 95% CI = 1.01–1.57), and between insulins and liver (n = 7; RR = 1.74; 95% CI = 1.08–2.80) and pancreatic cancers (n = 8; RR = 2.41; 95% CI = 1.08–5.36). Overall, biguanide and thiazolidinedione use carried no risk, or potentially lower risk of some cancers, while insulin secretagogue and insulin use were associated with increased pancreatic cancer risk. [ABSTRACT FROM AUTHOR]

Pemafibrate, a novel selective peroxisome proliferator-activated receptor modulator, has beneficial effects on lipid metabolism. However, its effects on glucose metabolism in individuals with type 2 diabetes (T2DM) remain to be fully clarified. This was a subanalysis of the PARM-T2D study, a multicenter prospective observational study on the use of pemafibrate versus conventional therapy for 52 weeks in subjects with T2DM complicated with hypertriglyceridemia. The subanalysis included participants who did not change their treatment for diabetes and did not receive insulin or insulin secretagogues during the study period. Changes in glucose metabolism markers, including homeostatic model assessment (HOMA2) scores and disposition index, were assessed. A total of 279 participants (141 in the pemafibrate group; 138 in the control group) met the criteria for the subanalysis. There were no significant changes in HbA1c during the 52-week study period in both groups. However, the pemafibrate group showed significant improvements versus the control group for insulin resistance assessed by HOMA2-R (−0.15 versus 0.08; estimated treatment difference −0.23 (95% confidence interval −0.44, −0.02); p = 0.03) and maintenance of β-cell function assessed by disposition index (0.015 versus −0.023; estimated treatment difference 0.037 (95% confidence interval 0.005, 0.069); p = 0.02). Correlation analyses showed that improvements in HOMA2-R and disposition index were significantly associated with improvements in lipid abnormalities and γ-glutamyl transpeptidase. In conclusion, pemafibrate reduced insulin resistance and maintained β-cell function in subjects with T2DM and hypertriglyceridemia, presumably by improving lipid profiles and lipid-related hepatocyte stress. [ABSTRACT FROM AUTHOR]

Background and Objectives: The objective is to evaluate medication adherence level (MA) and the relevant determinants of MA among patients with type 2 diabetes mellitus (T2DM) monitored in ambulatory settings by general practitioners. Materials and Methods: A cross-sectional study was conducted among patients with T2DM monitored in a GP practice in Sofia, Bulgaria (September–December 2022). All patients were interviewed according to a predesigned questionnaire after granting informed consent. MA level was evaluated through the Morisky–Green four-item questionnaire, and health-related quality of life was evaluated by EQ-5D-5L and VAS (visual analogue scale). Data were aggregated and statistically evaluated. Results: The total number of observed patients was 93. Around 48.4% of patients were female, and 90.3% of patients were between 50 and 80 years of age. Multimorbidity was identified among 70% (n = 65) of the respondents. High and medium levels of MA were revealed in 64.51% and 33.3% of respondents, respectively. Patients treated with insulin secretagogues were most adherent to the therapy (n = 83.3%) in comparison with the other treatment groups. The onset of the disease, professional status, age, gender, number of therapies, and quality of life did not affect the level of MA (p > 0.05). VAS scores among nonsmokers (VAS = 63.16 ± 20.45 vs. 72.77 ± 14.3) and non-consumers of alcohol (VAS = 63.91 ± 19.34 vs. VAS = 72.54 ± 15.98) were statistically significant lower (p < 0.05). A significant related factor for MA was years lived with diabetes (OR = 3.039, 95% CI 1.1436–8.0759, p = 0.0258). The longer the disease duration, the more the odds for a high MA level increased. Conclusions: The number of nonadherent diabetic patients in Bulgaria is low, which might be evidence of patients' concern about their own health and understanding about the importance of prescribed therapy. Further comprehensive study with additional patients is required to confirm the results and investigate the predicting factors for a high level of MA. [ABSTRACT FROM AUTHOR]

Aim: To assess whether the beta‐cell function of inpatients undergoing antidiabetic treatment influences achieving time in range (TIR) and time above range (TAR) targets. Materials and Methods: This cross‐sectional study included 180 inpatients with type 2 diabetes. TIR and TAR were assessed by a continuous glucose monitoring system, with target achievement defined as TIR more than 70% and TAR less than 25%. Beta‐cell function was assessed by the insulin secretion‐sensitivity index‐2 (ISSI2). Results: Following antidiabetic treatment, logistic regression analysis showed that lower ISSI2 was associated with a decreased number of inpatients achieving TIR (OR = 3.10, 95% CI: 1.19‐8.06) and TAR (OR = 3.40, 95% CI: 1.35‐8.55) targets after adjusting for potential confounders. Similar associations still existed in those participants treated with insulin secretagogues (TIR: OR = 2.91, 95% CI: 0.90‐9.36, P =.07; TAR, OR = 3.14, 95% CI: 1.01‐9.80) or adequate insulin therapy (TIR: OR = 2.84, 95% CI: 0.91‐8.81, P =.07; TAR, OR = 3.24, 95% CI: 1.08‐9.67). Furthermore, receiver operating characteristic curves showed that the diagnostic value of the ISSI2 for achieving TIR and TAR targets was 0.73 (95% CI: 0.66‐0.80) and 0.71 (95% CI: 0.63‐0.79), respectively. Conclusions: Beta‐cell function was associated with achieving TIR and TAR targets. Stimulating insulin secretion or exogenous insulin treatment could not overcome the disadvantage of lower beta‐cell function on glycaemic control. [ABSTRACT FROM AUTHOR]

Endogenous hyperinsulinemic hypoglycemia (EHH) is a rare condition with an incidence of approximately 4-6 per million person-years and comprises a group of disorders causing hyperinsulinemic hypoglycemia without exogenous administration of insulin or its secretagogues. In adults, most cases (approximately 90%) are secondary to a single insulinoma. Other causes include insulinoma in the context of multiple endocrine neoplasia type 1 (approximately 5% of cases) and non-insulinoma pancreatogenous hypoglycemia syndrome, which is estimated to account for 0.5-5% of all cases. Recently, an entity called insulinomatosis has been described as a novel cause of EHH in adults. The characteristic feature of insulinomatosis is the synchronous or metachronous occurrence of multiple pancreatic neuroendocrine tumors expressing exclusively insulin. While most cases arise sporadically, there is recent evidence that autosomal dominant inheritance of mutations in the v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) gene can cause a familial form of insulinomatosis. In these families, EHH is paradoxically associated with the occurrence of diabetes mellitus within the same family. This review summarizes the current clinical, biochemical, imaging and genetic knowledge of this disease. [ABSTRACT FROM AUTHOR]

The stimulus-secretion coupling of a glucose-induced release is generally attributed to the metabolism of the hexose in the β-cells in the glycolytic pathway and the citric acid cycle. Glucose metabolism generates an increased cytosolic concentration of ATP and of the ATP/ADP ratio that closes the ATP-dependent K+-channel at the plasma membrane. The resultant depolarization of the β-cells opens voltage-dependent Ca2+-channels at the plasma membrane that triggers the exocytosis of insulin secretory granules. The secretory response is biphasic with a first and transient peak followed by a sustained phase. The first phase is reproduced by a depolarization of the β-cells with high extracellular KCl maintaining the KATP-channels open with diazoxide (triggering phase); the sustained phase (amplifying phase) depends on the participation of metabolic signals that remain to be determined. Our group has been investigating for several years the participation of the β-cell GABA metabolism in the stimulation of insulin secretion by three different secretagogues (glucose, a mixture of L-leucine plus L-glutamine, and some branched chain alpha-ketoacids, BCKAs). They stimulate a biphasic secretion of insulin accompanied by a strong suppression of the intracellular islet content of gamma-aminobutyric acid (GABA). As the islet GABA release simultaneously decreased, it was concluded that this resulted from an increased GABA shunt metabolism. The entrance of GABA into the shunt is catalyzed by GABA transaminase (GABAT) that transfers an amino group between GABA and alpha-ketoglutarate, resulting in succinic acid semialdehyde (SSA) and L-glutamate. SSA is oxidized to succinic acid that is further oxidized in the citric acid cycle. Inhibitors of GABAT (gamma-vinyl GABA, gabaculine) or glutamic acid decarboxylating activity (GAD), allylglycine, partially suppress the secretory response as well as GABA metabolism and islet ATP content and the ATP/ADP ratio. It is concluded that the GABA shunt metabolism contributes together with the own metabolism of metabolic secretagogues to increase islet mitochondrial oxidative phosphorylation. These experimental findings emphasize that the GABA shunt metabolism is a previously unrecognized anaplerotic mitochondrial pathway feeding the citric acid cycle with a β-cell endogenous substrate. It is therefore a postulated alternative to the proposed mitochondrial cataplerotic pathway(s) responsible for the amplification phase of insulin secretion. It is concluded the new postulated alternative suggests a possible new mechanism of β-cell degradation in type 2 (perhaps also in type 1) diabetes. [ABSTRACT FROM AUTHOR]

This article provides practical tips for advising people with type 2 diabetes on how to engage in regular exercise safely and effectively. Its focus is on individuals who wish to exceed the minimum physical activity recommendation of 150 minutes/week of moderate-intensity exercise or even compete in their chosen sport. Health care professionals who work with such individuals must have a basic understanding of glucose metabolism during exercise, nutritional requirements, blood glucose management, medications, and sport-related considerations. This article reviews three key aspects of individualized care for physically active people with type 2 diabetes: 1) initial medical assessment and pre-exercise screenings, 2) glucose monitoring and nutritional considerations, and 3) the combined glycemic effects of exercise and medications. [ABSTRACT FROM AUTHOR]

This editorial comments on the article by Lipska et al. in this issue. [ABSTRACT FROM AUTHOR]

The article discusses the significant impact of obesity on diabetes management and the advancements in pharmacotherapy aimed at addressing both conditions. Topics include the development of incretin mimetics and their advantages in treating obesity and diabetes; the introduction of tirzepatide as a dual agonist that shows improved outcomes over traditional GLP-1 agonists; and the ongoing clinical trials assessing the effectiveness of retatrutide.

Background: The comparative safety of sulfonylureas (SUs) in nursing home (NH) residents remains understudied despite widespread use. We compared the effects of three SU medications and initial SU doses on adverse glycemic and cardiovascular events among NH residents. Methods: This national retrospective cohort study linked Medicare claims with Minimum Data Set 2.0 assessments for long‐stay NH residents aged ≥65 years between January 2008 and September 2010. Exposures were the SU medication initiated (glimepiride, glipizide, or glyburide) and doses (standard or reduced). One‐year outcomes were hospitalizations or emergency department visits for severe hypoglycemia, heart failure (HF), stroke, and acute myocardial infarction (AMI). After the inverse probability of treatment and inverse probability of censoring by death weighting, we estimated hazard ratios (HR) using Cox regression models with robust 95% confidence intervals (CI). Results: The cohort (N = 6821) included 3698 new glipizide, 1754 glimepiride, and 1369 glyburide users. Overall, the mean (standard deviation) age was 81.4 (8.2) years, 4816 (70.6%) were female, and 5164 (75.7%) were White non‐Hispanic residents. The rates of severe hypoglycemia were 30.3 (95% CI 22.3–40.1), 49.0 (95% CI 34.5–67.5), and 35.9 (95% CI 22.2–54.9) events per 1000 person‐years among new glipizide, glimepiride, and glyburide users, respectively (glimepiride versus glipizide HR 1.6, 95% CI 1.0–2.4, p = 0.04; glyburide versus glipizide HR 1.2, 95% CI 0.7–1.9, p = 0.59). The rates of severe hypoglycemia were 27.1 (95% CI 18.6–38.0) and 42.8 (95% CI 33.6–53.8) events per 1000 person‐years among new users of reduced and standard SU doses, respectively (HR 2.2, 95% CI 1.4–3.5, p < 0.01). Rates of HF, stroke, and AMI were similar between medications and doses. Conclusions: Among long‐stay NH residents, new use of glimepiride and standard SU doses resulted in higher rates of severe hypoglycemic events. Cardiovascular outcomes may not be affected by the choice of SU medication or dose. [ABSTRACT FROM AUTHOR]