Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

Glycemic control and diabetes complications across health status categories in older adults treated with insulin or insulin secretagogues: The Diabetes & Aging Study.

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.

Investigation of the relationship between the attitudes of patients with type 2 diabetes toward insulin therapy and complementary alternative medicine.

AIM: This study aimed to determine the attitudes of patients with type 2 diabetes toward insulin treatment and complementary alternative medicine and to examine the relationship between them. METHOD: A cross-sectional design was used in the study. A total of 293 patients with type 2 diabetes were included in the study. The study data were collected by using a Descriptive Information Form, Complementary, Alternative and Conventional Medicine Attitude Scale (CACMAS), and the Insulin Treatment Appraisal Scale (ITAS). The factors related to the attitudes of patients with type 2 diabetes toward insulin were examined by using multiple linear regression analysis. RESULTS: It was determined that 36.5% of the patients used CAM, 49.8% received insulin therapy, and that 38.6% received oral antidiabetic treatment. Patients' mean score on the total CACMAS was 106.8 ± 19.7, indicating a moderately positive attitude. Their mean score on the total ITAS was 57.1 ± 11.6, suggesting that they had a negative attitude toward insulin therapy. In regular drug use, negative attitudes toward insulin decreased (ß = -0.151, p < 0.001), and when dissatisfaction with conventional medicine increased, negative attitudes toward insulin increased, as well (ß = -0.432p<0.05). CONCLUSION: While almost all of the patients (93.9%) had a negative attitude toward insulin, they had a moderately positive attitude toward the use of CAM. A significant portion of them (36.5%) stated that they used CAM. There was a weak positive correlation between attitude toward CAM and negative attitude toward insulin.

High-dose insulin should be used before vasopressors/inotropes in calcium-channel blocker toxicity.

High-dose insulin (HDI) therapy with adapted glucose supplementation to maintain euglycaemia has been suggested to treat calcium-channel blocker (CCB) poisonings. Its underlying mechanisms of action are now well documented. We present a narrative review of the published experimental studies, case reports and experts' opinions to support the effectiveness and safety of HDI in the treatment of CCB poisoning. Our review strongly encourages the use of HDI as first-line therapy in CCB-poisoned patients in the presence of cardiovascular compromise, especially if cardiac function impairment has been diagnosed, before, but without delaying, the administration of vasopressors/inotropic drugs.

Laurus nobilis ethanolic extract attenuates hyperglycemia and hyperinsulinemia-induced insulin resistance in HepG2 cell line through the reduction of oxidative stress and improvement of mitochondrial biogenesis - Possible implication in pharmacotherapy.

The aim of this study was to establish the potential effect of Laurus nobilis ethanolic extract on improving insulin sensitivity and protecting liver cells from apoptosis, mitochondrial dysfunction, oxidative stress (OS), and inflammation; all of which considered as major alterations occurring during insulin resistance (IR) as well as diabetes onset, in hyperinsulinemic and hyperglycemic-induced HepG2 cell line. Thereby, L. nobilis ethanolic extract has been first chemically characterized using LC-MS/MS technique. Subsequently, HepG2 cells were pre-treated with an optimal concentration of L. nobilis ethanolic extract for 24 h, and then, subjected to 30 mM D-glucose and 500 nM insulin mixture for another 24 h in order to induce hyperinsulinemia and hyperglycaemia (HI/HG) status. Several parameters such as biocompatibility, hepatotoxicity, reactive oxygen species (ROS), mitochondrial transmembrane potential, dynamics, and metabolism, multicaspase activity, glucose uptake, in addition to genes and proteins expression levels were investigated. The obtained results showed that the bioactive extract of Laurus nobilis increased the number of living cells and their proliferation rate, significantly attenuated apoptosis by modulating pro-apoptotic pathways (p21, p53 and Bax genes), allowed a relative normalization of caspases-activity, and decreased the expression of inflammatory markers including c-Jun, NF-κB and Tlr4 transcripts. L. Nobilis ethanolic extract reduced considerably total intracellular ROS levels in challenged HepG2 cells, and regulated the mitochondrial OXPHOS pathway, demonstrating the potential antioxidant effect of the plant. Ethanolic plant extract increased insulin sensitivity, since an elevated expression of master transcripts responsible for insulin sensitivity including IRS1, IRS2, INSR was found. Taken together, obtained data suggest that L. nobilis ethanolic extract offers new insights in the development of potential antioxidant, insulin sensitizing as well as hepatoprotective drugs.

Nanoparticles of Antroquinonol-Rich Extract from Solid-State-Cultured Antrodia cinnamomea Improve Reproductive Function in Diabetic Male Rats.

PURPOSE: To characterize the nanoparticle of antroquinonol from A. cinnamomea and its ameliorative effects on the reproductive dysfunction in the diabetic male rat. MATERIAL AND METHODS: The chitosan-silicate nanoparticle was used as the carrier for the delivery of antroquinonol from solid-state-cultured A. cinnamomea extract (AC). The rats were fed with a high-fat diet and intraperitoneally injected with streptozotocin to induce diabetes. The rats were daily oral gavage by water [Diabetes (DM) and Control groups], three different doses of chitosan-silicate nanoparticle of antroquinonol from solid-state-cultured A. cinnamomea (nano-SAC, NAC): (DM+NAC1x, 4 mg/kg of body weight; DM+NAC2x, 8 mg/kg; and DM+NAC5x, 20 mg/kg), solid-state-cultured AC (DM+AC5x, 20 mg/kg), or metformin (DM+Met, 200 mg/kg) for 7 weeks. RESULTS: The nano-SAC size was 37.68±5.91 nm, the zeta potential was 4.13±0.49 mV, encapsulation efficiency was 79.29±0.77%, and loading capacity was 32.45±0.02%. The nano-SAC can improve diabetes-induced reproductive dysfunction by regulating glucose, insulin, and oxidative enzyme and by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, and sperm count as well as sperm mobility. In testicular histopathology, the seminiferous tubules of A. cinnamomea-supplemented diabetic rats showed similar morphology with the control group. CONCLUSION: The nanoparticle of antroquinonol from Antrodia cinnamomea can be used as an effective strategy to improve diabetes-induced testicular dysfunction.

Treating type 2 diabetes in COVID-19 patients: the potential benefits of injective therapies.

The coronavirus disease 2019 (COVID-19) has been declared as pandemic by the World Health Organization and is causing substantial morbidity and mortality all over the world. Type 2 diabetes, hypertension, and cardiovascular disease significantly increase the risk for hospitalization and death in COVID-19 patients. Hypoglycemia and hyperglycemia are both predictors for adverse outcomes in hospitalized patients. An optimized glycemic control should be pursued in patients with diabetes and SARS-CoV-2 infection in order to reduce the risk of severe COVID-19 course. Both insulin and GLP-1RAs have shown optimal glucose-lowering and anti-inflammatory effects in type 2 diabetic patients and may represent a valid therapeutic option to treat asymptomatic and non-critically ill COVID-19 diabetic patients.

Decreasing Hypoglycemia following Insulin Administration for Inpatient Hyperkalemia.

BACKGROUND: Acute hyperkalemia (serum potassium ≥ 5.1 mEq/L) is often treated with a bolus of IV insulin. This treatment may result in iatrogenic hypoglycemia (glucose < 70 mg/dl). OBJECTIVES: The aims of this study were to accurately determine the frequency of iatrogenic hypoglycemia following insulin treatment for hyperkalemia, and to develop an electronic health record (EHR) orderset to decrease the risk for iatrogenic hypoglycemia. DESIGN: This study was an observational, prospective study. SETTING: The setting for this study was a university hospital. PATIENTS: All nonobstetric adult inpatients in all acute and intensive care units were eligible. INTERVENTION: Implementation of a hyperkalemia orderset (Orderset 1.1) with glucose checks before and then one, two, four, and six hours after regular intravenous insulin administration. Based on the results from Orderset 1.1, Orderset 1.2 was developed and introduced to include weight-based dosing of insulin options, alerts identifying patients at higher risk of hypoglycemia, and tools to guide decision-making based on the preinsulin blood glucose level. MEASUREMENTS: Patient demographics, weight, diabetes history, potassium level, renal function, and glucose levels were recorded before, and then glucose levels were measured again at one, two, four, and six hours after insulin was administered. RESULTS: The iatrogenic hypoglycemia rate identified with mandatory glucose checks in Orderset 1.1 was 21%; 92% of these occurred within three hours posttreatment. Risk factors for hypoglycemia included decreased renal function (serum creatinine >2.5 mg/dl), a high dose of insulin (>0.14 units/kg), and re-treatment with blood glucose < 140 mg/dl. After the introduction of Orderset 1.2, the rate of iatrogenic hypoglycemia decreased to 10%. CONCLUSIONS: The use of an EHR orderset for treating hyperkalemia may reduce the risk of iatrogenic hypoglycemia in patients receiving insulin while still adequately lowering their potassium.

Ventricular bigeminy and trigeminy caused by hypophosphataemia during diabetic ketoacidosis treatment: a case report.

BACKGROUND: Hypophosphatemia has many causes, and is often encountered during DKA (Diabetic Ketoacidosis) treatment. However, it rarely requires clinical intervention. CASE PRESENTATION: Ventricular arrhythmia was observed in a 10-year-old girl with newly diagnosed type 1 diabetes mellitus and hypophosphatemia while undergoing treatment for ketoacidosis. Oral phosphate supplementation ceased ventricular arrhythmia almost completely. CONCLUSIONS: The clinical signs of hypophosphatemia are potentially life-threatening. Therefore, physicians should be vigilant when treating patients who are at risk of hypophosphatemia. Severe hypophosphatemia accompanied by clinical symptoms requires oral or intravenous supplementation of phosphate.

Fully closed-loop insulin delivery in inpatients receiving nutritional support: a two-centre, open-label, randomised controlled trial.

BACKGROUND: Glucose management is challenging in patients who require nutritional support in hospital. We aimed to assess whether fully closed-loop insulin delivery would improve glycaemic control compared with conventional subcutaneous insulin therapy in inpatients receiving enteral or parenteral nutrition or both. METHODS: We did a two-centre (UK and Switzerland), open-label, randomised controlled trial in adult inpatients receiving enteral or parenteral nutrition (or both) who required subcutaneous insulin therapy. Patients recruited from non-critical care surgical and medical wards were randomly assigned (1:1) using a computer-generated minimisation schedule (stratified by type of nutritional support [parenteral nutrition on or off] and pre-study total daily insulin dose [<50 or ≥50 units]) to receive fully closed-loop insulin delivery with faster-acting insulin aspart (closed-loop group) or conventional subcutaneous insulin therapy (control group) given in accordance with local clinical practice. Continuous glucose monitoring in the control group was masked to patients, ward staff, and investigators. Patients were followed up for a maximum of 15 days or until hospital discharge. The primary endpoint was the proportion of time that sensor glucose concentration was in target range (5·6-10·0 mmol/L), assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01774565. FINDINGS: Between Feb 8, 2018, and Sept 21, 2018, 90 patients were assessed for eligibility, of whom 43 were enrolled and randomly assigned to the closed-loop group (n=21) or the control group (n=22). The proportion of time that sensor glucose was in the target range was 68·4% [SD 15·5] in the closed-loop group and 36·4% [26·6] in the control group (difference 32·0 percentage points [95% CI 18·5-45·5; p<0·0001]). One serious adverse event occurred in each group (one cardiac arrest in the control group and one episode of acute respiratory failure in the closed-loop group), both of which were unrelated to study interventions. There were no adverse events related to study interventions in either group. No episodes of severe hypoglycaemia or hyperglycaemia with ketonaemia occurred in either study group. INTERPRETATION: Closed-loop insulin delivery is an effective treatment option to improve glycaemic control in patients receiving nutritional support in hospital. FUNDING: Diabetes UK, Swiss National Science Foundation, National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Trust, and European Foundation for the Study of Diabetes.

Severe Hypoglycemia Due to Cryptic Insulin Use in a Bodybuilder.

BACKGROUND: Bodybuilding is a demanding sport, which requires high-volume, high-resistance weight training and augmented nutritional intake, toward an increase of overall body muscle mass accompanied by an overall decrease of body fat percentage and mass. Among bodybuilders, the use of various legal and illegal supplements is common. These supplements may be naturally occurring or man-made. CASE REPORT: We discuss the case of a 30-year-old male bodybuilder presenting with coma due to severe hypoglycemia from unknown cause, necessitating iterative glucose infusions, which was subsequently found to be related to cryptic insulin injections. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In strength athletes, especially amateurs, the recourse to performance-enhancement drugs (e.g., insulin) is frequent. Beyond the specificity of care required for surreptitious insulin intoxication, emergency physicians should be alert to the possibility that exogenous insulin has been injected for use as an ergogenic aid by bodybuilders and others seeking to increase their body muscle mass when they encounter a patient with a decreased level of consciousness and treatment-refractory hypoglycemia. Moreover, in case of suspicion of such intoxication, the use of other illegal supplements should be screened, due to potentially associated risks of complication.

Noninsulin medication therapy for hospitalized patients with diabetes mellitus.

PURPOSE: Published evidence regarding the role of noninsulin antidiabetic therapies in glycemic management of hospitalized patients with diabetes mellitus is reviewed. SUMMARY: The American Diabetes Association recommends against the routine use of noninsulin antidiabetic therapies during hospitalization and supports insulin use instead. There are significant risks associated with insulin therapy, including hypoglycemia, and use of alternative therapies may be considered in hospitalized patients. A MEDLINE literature search was conducted to find articles on studies evaluating the use of noninsulin antidiabetic therapies in the inpatient setting; all full-text English-language publications presenting observational and randomized clinical trial data on the topic of interest were considered for inclusion in the review, with 9 publications selected for review. The majority of the reviewed research focused on incretin-based therapies, and favorable safety and efficacy outcomes were reported with the use of dipeptidyl peptidase-4 (DPP-4) inhibitors. The available evidence indicates that the use of other noninsulin medications, including glucagon-like peptide-1 receptor agonists and sulfonylureas, to achieve and maintain glycemic control in the inpatient setting may be limited by adverse effects. CONCLUSION: Optimal glycemic control in hospitalized patients with diabetes is necessary to avoid adverse effects. Insulin therapy is currently the primary medication recommended for this patient population. DPP-4 inhibitors have been demonstrated to be safe and effective for use in the inpatient setting in patients with well-controlled diabetes. Further research is needed to help define the role of noninsulin medications in the inpatient setting.

Intranasal glucagon for hypoglycaemia in diabetic patients. An old dream is becoming reality?

In 1983 it was shown that glucagon administered intranasally (IN) was absorbed through the nasal mucosa and increased blood glucose in healthy subjects. Shortly thereafter, it was shown that IN glucagon counteracts with hypoglycaemia in insulin-treated diabetic patients. In spite of this evidence, IN glucagon was not developed by any pharmaceutical company before 2010, when renewed interest led to intensive evaluation of a possible remedy for hypoglycaemia in insulin-treated diabetic adults and children. IN glucagon is now being developed as a needle-free device that delivers glucagon powder for treatment of severe hypoglycaemia; the ease of using this device stands in stark contrast to the difficulties encountered in use of the current intramuscular glucagon emergency kits. Studies have demonstrated the efficacy, safety and ease-of-use of this IN glucagon preparation, and suggest IN glucagon as a promising alternative to injectable glucagon for treating severe hypoglycaemia in children and adults who use insulin. This would meet the unmet medical need for an easily administered glucagon preparation.

High dose insulin for beta-blocker and calcium channel-blocker poisoning.

BACKGROUND/OBJECTIVES: High dose insulin (HDI) is a standard therapy for beta-blocker (BB) and calcium channel-blocker (CCB) poisoning, however human case experience is rare. Our poison center routinely recommends HDI for shock from BBs or CCBs started at 1U/kg/h and titrated to 10U/kg/h. The study objective was to describe clinical characteristics and adverse events associated with HDI. METHODS: This was a structured chart review of patients receiving HDI for BB or CCB poisoning with HDI defined as insulin infusion of ≥0.5U/kg/h. RESULTS: In total 199 patients met final inclusion criteria. Median age was 48years (range 14-89); 50% were male. Eighty-eight patients (44%) were poisoned by BBs, 66 (33%) by CCBs, and 45 (23%) by both. Median nadir pulse was 54 beats/min (range 12-121); median nadir systolic blood pressure was 70mmHg (range, 30-167). Forty-one patients (21%) experienced cardiac arrest; 31 (16%) died. Median insulin bolus was 1U/kg (range, 0.5-10). Median starting insulin infusion was 1U/kg/h (range 0.22-10); median peak infusion was 8U/kg/h (range 0.5-18). Hypokalemia occurred in 29% of patients. Hypoglycemia occurred in 31% of patients; 50% (29/50) experienced hypoglycemia when dextrose infusion concentration ≤10%, and 30% (31/105) experienced hypoglycemia when dextrose infusion concentration ≥20%. CONCLUSIONS: HDI, initiated by emergency physicians in consultation with a poison center, was feasible and safe in this large series. Metabolic abnormalities were common, highlighting the need for close monitoring. Hypoglycemia was more common when less concentrated dextrose maintenance infusions were utilized.

Cost calculation for a flash glucose monitoring system for UK adults with type 1 diabetes mellitus receiving intensive insulin treatment.

AIMS: To estimate the costs associated with a flash glucose monitoring system as a replacement for routine self-monitoring of blood glucose (SMBG) in patients with type 1 diabetes mellitus (T1DM) using intensive insulin, from a UK National Health Service (NHS) perspective. METHODS: The base-case cost calculation was created using the maximum frequency of glucose monitoring recommended by the 2015 National Institute for Health and Care Excellence guidelines (4-10 tests per day). Scenario analyses considered SMBG at the frequency observed in the IMPACT clinical trial (5.6 tests per day) and at the frequency of flash monitoring observed in a real-world analysis (16 tests per day). A further scenario included potential costs associated with severe hypoglycaemia. RESULTS: In the base case, the annual cost per patient using flash monitoring was £234 (19%) lower compared with routine SMBG (10 tests per day). In scenario analyses, the annual cost per patient of flash monitoring compared with 5.6 and 16 SMBG tests per day was £296 higher and £957 lower, respectively. The annual cost of severe hypoglycaemia for flash monitoring users was estimated to be £221 per patient, compared with £428 for routine SMBG users (based on 5.6 tests/day), corresponding to a reduction in costs of £207. CONCLUSIONS: The flash monitoring system has a modest impact on glucose monitoring costs for the UK NHS for patients with T1DM using intensive insulin. For people requiring frequent tests, flash monitoring may be cost saving, especially when taking into account potential reductions in the rate of severe hypoglycaemia.

Mindfulness and fear of hypoglycaemia in parents of children with Type 1 diabetes: results from Diabetes MILES Youth - The Netherlands.

AIMS: To identify the sociodemographic and clinical correlates of fear of hypoglycaemia among parents of children (aged 4-18 years) with Type 1 diabetes and to examine the relationships between parental fear of hypoglycaemia, mindfulness and mindful parenting. METHODS: Sociodemographic, self-reported clinical and psychological data were extracted from the cross-sectional Diabetes MILES Youth - The Netherlands dataset. Questionnaires included the Hypoglycaemia Fear Survey - Parent Worry (parental fear of hypoglycaemia), the Freiburg Mindfulness Inventory - Short version (mindfulness) and the Interpersonal Mindfulness in Parenting Scale (mindful parenting). RESULTS: A total of 421 parents (359 mothers) participated. Hierarchical linear regression analyses showed that greater parental fear of hypoglycaemia was related to younger parental age, low educational level, non-Dutch nationality, more frequent blood glucose monitoring, and less general mindfulness. Adding mindful parenting to the model negated the previous contribution of general mindfulness. In this model, lower mindful parenting was related to greater parental fear of hypoglycaemia. In particular, parents with an increased ability to be less judgemental of themselves as parents and less reactive to emotions within parenting interactions reported less fear of hypoglycaemia. In total, 21% of the variance in parental fear of hypoglycaemia was explained. CONCLUSION: Parental fear of hypoglycaemia was associated largely with parental characteristics, including non-modifiable sociodemographics (i.e. age, education, nationality) and modifiable psychological factors (i.e. mindful parenting). These findings suggest that it is important to further explore mindfulness-based interventions for parents to reduce fear of hypoglycaemia next to interventions to reduce hypoglycaemia.

Glycemic Variability and Insulin Needs in Patients with Type 1 Diabetes Mellitus Supplemented with Vitamin D: A Pilot Study Using Continuous Glucose Monitoring System.

BACKGROUND: Recent studies suggest that glycemic variability could influence the risk of complications in Type 1 Diabetes Mellitus (T1DM). There are no data about the action of Vitamin D (VD) on glycemic variability. Our pilot study aims to evaluate glycemic variability and insulin needs in patients with T1DM supplemented with VD. METHODS: 22 Patients received doses of 4000 and 10000 IU/day of cholecalciferol for 12 weeks, according to the patient's baseline VD levels and underwent continuous glucose monitoring system. RESULTS: Correlations were found between percentage variation (Δ) of glycemia standard deviation (ΔSDG), calculated using continuous glucose monitoring, with Δ of basal (r = 0.6; p <0.01) and total insulin dose (r = 0.6; p <0.01). Correlations between VD status after supplementation and Δ of prandial (r = 0.5; p <0.05) and total insulin dose (r = 0.4; p <0.05) were found, suggesting that the dose of insulin needed by patients is lower when VD status is better. We divided patients in two subgroups: SDG improved (subgroup 1; N = 12 (55%)) and SDG worsened (subgroup 2; N = 10 (45%)). Group 1, compared to subgroup 2, required a lower insulin dose (Δbasal insulin dose = -8.0 vs. 6.3%; p <0.05) and had a lower frequency of hypoglycemia (27% vs. 64%, hypoglycemias/days evaluated; p <0.01). CONCLUSION: Our study suggests a relation between VD supplementation, improved glycemic variability, lower insulin needs and lower frequency of hypoglycemia in patients with T1DM.

Real-world evidence concerning clinical and economic outcomes of switching to insulin glargine 300 units/mL vs other basal insulins in patients with type 2 diabetes using basal insulin.

This retrospective cohort study compared real-world clinical and healthcare-resource utilization (HCRU) data in patients with type 2 diabetes using basal insulin (BI) who switched to insulin glargine 300 units/mL (Gla-300) or another BI. Data from the Predictive Health Intelligence Environment database 12 months before (baseline) and 6 months after (follow-up) the switch date (index date, March 1, 2015 to May 31, 2016) included glycated haemoglobin A1c (HbA1c), hypoglycaemia, HCRU and associated costs. Baseline characteristics were balanced using propensity score matching. Change in HbA1c from baseline was similar in both matched cohorts (n = 1819 in each). Hypoglycaemia incidence and adjusted event rate were significantly lower with Gla-300. Patients switching to Gla-300 had a significantly lower incidence of HCRU related to hypoglycaemia. All-cause and diabetes-related hospitalization and emergency-department HCRU were also favourable for Gla-300. Lower HCRU translated to lower costs in patients using Gla-300. In this real-world study, switching to Gla-300 reduced the risk of hypoglycaemia in patients with type 2 diabetes when compared with those switching to another BI, resulting in less HCRU and potential savings of associated costs.

Colecalciferol regula os parâmetros hematológicos e a produção de citocinas pró-inflamatórias renais em camundongos diabéticos e nas células RAW 264. 7 / Colecalciferol regulates haematological parameters and the production of renal proinflammatory cytokines in diabetic mice and RAW 264. 7 cells

Os efeitos causados pelo tratamento em conjunto da insulina e do colecalciferol em indivíduos diabéticos não estão completamente elucidados. O presente trabalho avaliou o efeito de ambos os hormônios nos rins, no fígado, no coração e nos parâmetros hematológicos de camundongos machos (C57BL/6) sadios e diabéticos, bem como a ação do colecalciferol (in vitro) na resposta imunológica desenvolvida pelas células RAW 264.7 e pelos macrófagos peritoneais (MP) após estímulo com lipopolissacarídeo (LPS). Após dez dias da administração da aloxana (60 mg/kg), animais diabéticos exibiram redução do ganho de peso corporal e hiperglicemia quando comparados aos animais que receberam salina. No sétimo dia do período experimental, foi verificado que animais diabéticos que não receberam nenhum hormônio, em relação aos não diabéticos, exibiram redução do peso corporal, dos níveis de hemoglobina (Hb), hematócrito, hematimetria, insulina, TNF-α e IL-6 (coração) e aumento da glicemia, da relação peso corpóreo/peso rim esquerdo, das concentrações séricas de ureia, creatinina, Fosfatase Alcalina (FAL), Lactato desidrogenase (LDH) e lactato, fator de necrose tumoral (TNF)-α, interleucina (IL)-6 e IL-10 (no rim); o tratamento com insulina (1 UI/300 mg/dL glicemia), em relação aos animais diabéticos não tratados, promoveu aumento do peso corporal, das concentrações séricas de insulina e redução da glicemia, das concentrações séricas de ureia e da razão TNF-α/IL-10 (coração); o tratamento com colecalciferol (800 UI/dia), em relação aos animais diabéticos não tratados, promoveu aumento das concentrações séricas de 25-hidroxicolecalciferol [25(OH)D], Hb, hematócrito, hematimetria, IL-10 (coração) e reduziu IL-6, IL-10, TNF-α e EPO (rim); os animais diabéticos tratados com insulina, em relação aos animais diabéticos suplementados com colecalciferol apresentaram aumento do peso corpóreo, de ureia sérica, IL-6 e TNF-α (coração) e redução da glicemia, das concentrações séricas de lactato, de IL-6, TNF-α, IL-10 e EPO (rim); os animais -que receberam ambos os hormônios, em relação aos animais tratados com insulina, apresentaram aumento sérico de insulina e lactato; os animais diabéticos que receberam ambos os hormônios, em relação aos animais diabéticos tratados com colecalciferol, exibiram aumento sérico de 25(OH)D, de insulina, além da redução das concentrações de IL-10, da razão de TNF-α/IL-10 e TNF-α/IL-6 (coração); animais diabéticos que receberam ambos os hormônios, em relação aos diabéticos não suplementados com colecalciferol, exibiram: aumento de insulina sérica e redução das concentrações séricas de ureia e das razões renal e hepática de TNF-α/IL-6; células RAW 264.7 estimuladas pelo LPS e tratadas com 100 nM colecalciferol exibiram maior expressão da CYP27B1 e redução na liberação de mediadores inflamatórios quando comparadas ao grupo estimulado pelo LPS. Entretanto, não foi observado o mesmo efeito nos MP. Em conjunto, os resultados sugerem que: 1) em animais diabéticos, o colecalciferol pode modular parâmetros hematológicos e que a insulina pode melhorar a função renal, bem como a recuperação do peso corporal; 2) o colecalciferol pode ser metabolizado pelas células RAW 264.7 e modular a resposta imunológica desencadeada pelo LPS

The effects caused by the treatment of insulin and cholecalciferol in diabetic subjects are not completely elucidated. The present study evaluated the effect of both hormones on the kidneys, liver, heart and hematological parameters of healthy and diabetic male mice (C57BL/6), as well as the action of cholecalciferol (in vitro) on the immune response developed by the cells RAW 264.7 and peritoneal macrophages (MP) after stimulation with lipopolysaccharide (LPS). After ten days of alloxan administration (60 mg/kg), diabetic animals exhibited a reduction in body weight gain and hyperglycemia when compared to animals that received saline. On the seventh day of the experimental period, it was verified that diabetic animals that did not receive any hormones, in relation to non-diabetics, showed reduction of body weight, hemoglobin (Hb), hematocrit, hematimetry, insulin, TNF-α and IL- 6 (heart) and increased glycemia, body weight / left kidney weight, serum urea, creatinine, Phosphatase Alkaline, lactate dehydrogenase (LDH) and lactate levels, tumor necrosis factor (TNF) interleukin (IL) -6 and IL-10 (in the kidney); diabetic mice treated with insulin (1 IU / 300 mg/dL glycemia) in relation to untreated diabetic animals promoted increased body weight, serum insulin levels and blood glucose lowering, serum urea levels and TNF-α ratio / IL-10 (heart); diabetic animals treated with cholecalciferol (800 IU/day), in relation to untreated diabetic animals, exhibited increased serum levels of 25-hydroxycholecalciferol [25 (OH) D], Hb, hematocrit, hematimetry, IL-10 (heart) and reduced IL-6, IL-10, TNF-α and EPO (kidney);insulin-treated diabetic animals compared to diabetic animals supplemented with cholecalciferol exhibited an increase of body weight, serum urea, IL-6 and TNF-α (heart) and a reduction of glycaemia, serum lactate levels, IL-6, TNF- α, IL-10 and EPO (kidney); animals that received both hormones, compared to animals treated with insulin exhibited an increase of insulin and lactate serum levels; diabetic animals that received both hormones, compared to diabetic animals treated with cholecalciferol, exhibited an increase of 25(OH)D and insulin serum levels, and a reduction of IL-10, TNF-α/IL-10 and TNF-α/IL-6 ratios (heart); diabetic animals that received both hormones, compared to diabetic animals not supplemented with cholecalciferol, exhibited an increase of insulin and reduced urea serum levels and reduced renal and hepatic TNF-α/IL-6 ratios; LPS-stimulated RAW 264.7 cells and treated with 100 nM cholecalciferol exhibited greater CYP27B1 expression and reduced release of inflammatory mediators when compared to the LPS-stimulated group. However, the same effect was not observed in PM. Taken together, the results suggest that: 1) in diabetic animals, cholecalciferol may modulate hematological parameters and that insulin may improve renal function as well as recovery of body weight; 2) cholecalciferol can be metabolized by RAW 264.7 cells and modulate the immune response triggered by LPS