Multiple Insulin Injections Research Articles

Type 1 diabetes mellitus; ovarian reserve; anti-Müllerian hormone; ovarian function

BACKGROUND: Prolonged course of diabetes mellitus often leads to the development of vascular complications, insufficiency of ovarian function. The occurrence of diabetes mellitus in women before pregnancy (pregestational diabetes mellitus) it can have various adverse consequences for the mother, fetus, child and the course of pregnancy. Pregnancy planning in women with pregestational diabetes significantly improves the outcomes of pregnancy and childbirth. AIM: The aim of this study was to analyze gonadotropic and ovarian function parameters in patients with type 1 diabetes mellitus depending on the age of onset, duration and compensation level of the disease. MATERIALS AND METHODS: The patients included into this clinical prospective study were divided into two groups. The main group consisted of 216 patients with type 1 diabetes mellitus aged 18 to 39 years (mean age: 27.1 ± 3.1 years). The control group consisted of 30 healthy women of reproductive age. Chemiluminescent immunoassay was used to determine blood serum levels of anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, testosterone, free testosterone, and sex hormone-binding globulin from day 2 to day 5 of the menstrual cycle. Serum progesterone levels were measured on days 20–23 of the menstrual cycle for three consecutive cycles. Glycated hemoglobin levels were also studied in the blood serum of patients with type 1 diabetes mellitus. All the patients underwent pelvic ultrasound examination to assess the cohort of antral follicles and ovarian volume. RESULTS: The average age of menarche in patients with type 1 diabetes mellitus who developed the disease at the age of under 10 years was 14.2 ± 1.2 years. This was higher than in the group of girls with the onset of the disease over the age of 10 years (13.5 ± 1.2 years) and in women of the control group (11.9 ± 1.1 years). When assessing the ovarian reserve in patients with type 1 diabetes mellitus, we found a decrease in anti-Müllerian hormone level and antral follicle count in the group of women with disease onset at the age of under 10 years. We did not find differences in the ovarian reserve parameters in patients depending on disease duration. Normogonadotropic normoprolactinemic ovarian insufficiency was detected in 154 (71.3%) of 216 patients, while the rest 62 (28.7%) women had an ovulatory menstrual cycle. In patients with anovulation, luteal phase deficiency and ovulatory menstrual cycle, we found no differences between the age of development of type 1 diabetes mellitus, its duration, glycated hemoglobin levels, total daily insulin dose and insulin dose per kilogram of body mass. In patients receiving intensive insulin therapy with continuous subcutaneous insulin infusion, glycated hemoglobin level was lower than in those receiving multiple dose insulin injection therapy. CONCLUSIONS: The average age of menarche in patients with type 1 diabetes mellitus is higher than in healthy women. The ovarian reserve parameters in patients with early onset of the disease, before 10 years of age, are lower than in patients who developed type 1 diabetes mellitus after 10 years of age. Duration of pregnancy planning period depends on compensation level of the disease and lasts from six to 12 months. This requires the doctor and patient to prepare for the implementation of reproductive tasks as early as possible, especially in patients whose disease onset occurred in pre-pubertal period.

12201 Ketogenic-diet As A Trigger Of First Episode Diabetic Ketoacidosis In A Woman Living With Type 1 Diabetes Mellitus

Abstract Disclosure: M.E. Chacon Cruz: None. A.N. Gonzalez Bossolo: None. G.J. Mora Osoria: None. A number of dietary patterns have been proposed as an effective method for weight reduction. A keto diet is a strict low-carbohydrate and high-fat diet. The reduction in carbohydrates enables the body to rely on fat as a predominant energy source leading to a state of ketosis. However, a serious but rare complication of the ketogenic diet is ketoacidosis associated with low carbohydrate intake, which should be cautiously monitored in people with a predisposition to the condition, such patient with diabetes mellitus type 1. We report the case of a female patient living with type 1 diabetes mellitus female who developed her first episodes of diabetic ketoacidosis (DKA) as the following the course of ketogenic diet. A 53 y/o Female patient with past medical history diabetes mellitus type 1 and pernicious anemia went emergency department complaining pelvic pain associated with weakness, nausea and vomiting for about 1 day of evolution. Patient also refers that during the past 2 weeks she has been doing a detox and taking some herbal and tea. Other physical examinations were unremarkable except for moderate dehydration. The initial testing revealed patients meet criteria for severe diabetes ketoacidosis (DKA) with a pH: 7.04, CO2 15, serum central bicarbonate in 6 mmol/L and elevated blood glucose in 504 mg/dl and positive urine and serum ketones, C-Peptide less than 0.02 ng/ml. and glycosylated hemoglobin in 8.25%. She was admitted to the intensive care unit and treated with intravenous saline, intravenous insulin infusion, and electrolyte repletion. Blood glucose levels and metabolic acidosis improved. After DKA resolved patient refers that week started with Keto-diet and was restricting carbohydrates. Patient was discharge home with multiple injection insulin and followed by Endocrinologist services in the external clinic for a follow up. This case illustrates the challenges and the importance of dietary history providing clues to the diagnosis. If we had never asked her about her diet, we would not have found the reason that brought her to the DKA. This case demonstrates the development of DKA following ketogenic diet in a patient with type 1 diabetes. It is important for physicians to be aware of this rare potential complication of ketogenic diet which is infrequently reported in literature. Therefore, physicians should be cognizant of the complications and risks, and benefits of the ketogenic diet. Risks and benefits of the ketogenic diet should be discussed with patients before initiation of this diet. The patient was followed in an outpatient clinic with Endocrinologist service for evaluation for an insulin pump. Presentation: 6/1/2024

Interesting Life Journey of a Type 1 Diabetes Individual from the Era of Injectable Insulins to the Hybrid Closed-Loop Insulin Pump

Abstract Continuous subcutaneous insulin infusion (CSII) pump has shown good outcomes in individuals with diabetes. An individual with type 1 diabetes (T1D) was diagnosed in 1996 at the age of 14 years with GAD-positive and absent C Peptide reserves confirming the diagnosis. Initially, the individual was started with the conventional treatment for T1D consisting of multiple insulin injections per day, however, with this treatment, there was a wide fluctuation in the blood sugar levels with frequent hyperglycemic and hypoglycemic episodes, and could not achieve strict HbA1c control. In 2019, the treatment was switched to a 620G CSII pump, the fluctuations in blood sugar levels were reduced, but still, there were occasional hyperglycemic and hypoglycemic episodes failing to achieve the target HbA1c control. In 2022, again the treatment was changed to the latest 780G CSII pump termed the artificial pancreas which helped the person with T1D to achieve strict blood sugar level control and excellent ‘Time in Range’ with no hyperglycemic and hypoglycemic episodes and a better quality of life.

Results of a retrospective study of the clinical efficacy and safety of insulin RinFast® in children with type 1 diabetes mellitus

BACKGROUND: The relevance of the study is justified by the fact that in recent years, the original insulin preparations have been replaced with biosimilars in the regions of the Russian Federation, but there are currently few studies describing the use of insulin biosimilars in children with type 1 diabetes mellitus (DM1), both in domestic and foreign sources.AIM: To evaluate the efficacy and safety insulin therapy with RinFast® (GEROPHARM LLC, Russia) as bolus therapy in combination with long-acting insulin and as monotherapy in an insulin pump in children with DM1 in real clinical practice.MATERIALS AND METHODS: The dynamics of HbA1c after 3 and 6 months, the change in daily insulin requirements, the fre quency of episodes of postprandial hyper- and hypoglycemia, adverse reactions at injection sites, the number of patients who reached the target values of HbA1c in children with DM1 who received RinFast® at least 6 months after the original analogue of insulin aspart were evaluated.RESULTS: The study was conducted in 50 children with DM1 from 1 to 18 years old (average age 9.8±4.6 years), with a duration of DM1 of more than 1 year (average duration 3.5±2.1 years), who had glycated hemoglobin (HbA1c) at the beginning of follow-up of no more than 9.5% and received biosimilar RinFast® for at least 6 months after the transfer from the original analogue of insulin aspart. Basic bolus insulin therapy in 36 children was carried out using multiple injections of insulin (MII), in 14 — continuous supply of insulin (NPI) using an insulin pump. The study resulted in HbA1c levels comparable to the baseline 3 and 6 months after the start of therapy with the RinFast® biosimilar (p=0.05), no changes in the daily ­insulin ­requirement (p=0.05) and no increase in the frequency of episodes of postprandial hyper- (p=0.05) and hypoglycemia (p=0.05) and adverse events (p=0.05). High adherence to treatment with the RinFast® biosimilar was noted.CONCLUSION: The results obtained indicate the absence of a clinically significant deterioration in glycemic control indicators after the transfer of children with DM1 to therapy with the RinFast® biosimilar, which makes it possible to use it safely and effectively in this category of patients.

Effect of multiple insulin injections on estrus expression in cross bred cows

Effect of multiple insulin injections on estrus expression in cross bred cows

Functional insulin aspart/insulin degludec-based microneedles for promoting postprandial glycemic control.

Insulin aspart (IAsp) and insulin degludec (IDeg), as the third generation of insulin, have a faster onset time or a more durable action period, which may simulate the secretion of insulin under physiological conditions. Microneedles (MNs) are transdermal delivery devices that may allow diabetic patients to easily deploy transdermal insulin therapy while considerably reducing injection pain. In this study, we investigated the combination of dissolving MNs with IAsp or IDeg therapy as an alternative to daily multiple insulin injections, aiming to improve glycemic control and patient compliance. Mechanical properties of the MNs, structural stability of insulin encapsulated in the MNs, and transdermal application characteristics were studied to assess the practicality of insulin-loaded MNs for diabetes therapy. In vivo experiments conducted on diabetic rats demonstrated that the IAsp- and IDeg-loaded MNs have comparable blood glucose control abilities to that of subcutaneous injections. In addition, the therapeutic properties of insulin-loaded MNs under diverse dietary conditions and application strategies were further investigated to provide new information to support future clinical trials. Taken together, the proposed MNs have the potential to improve balances between glycemic control, hypoglycemia risk, and convenience, providing patients with simpler regimens. STATEMENT OF SIGNIFICANCE: 1. The fabricated functional insulin-loaded dissolving microneedles closely matched the glucose rise that occurs in response to meals, demonstrating promising alternatives for multiple daily insulin injections. 2. The hypoglycemic properties of insulin microneedles were investigated under diverse dietary conditions and application strategies, yielding new information to support future clinical trials. 3. Molecular dynamics simulations were utilized to study the interactions between the insulin and microneedle matrix materials, providing a strategy for theoretically understanding drug stability as well as the release mechanism of drug-loaded microneedles.

2023 Clinical Practice Guidelines for Diabetes

The Committee on Clinical Practice Guidelines of the Korean Diabetes Association updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the eighth edition in May 2023. We performed a comprehensive systematic review of recent clinical trials and evidence suitable for the Korean population that could be applicable to real-world practice. These guidelines were developed to enable all healthcare providers including physicians, diabetes experts, and certified diabetes educators nationwide to best care for individuals with diabetes in a clinical practice setting. The recommendations for screening, medical nutrition therapy, pharmacologic therapy for adults with type 2 diabetes, and obesity, hypertension, and lipid management were revised and updated. The use of real-time continuous glucose monitoring (CGM) devices was recommended for adults with type 1 diabetes and adults with type 2 diabetes treated with multiple insulin injections, and additional CGM metrics were added to the blood glucose control target.

Pharmacoepidemiological analysis of type 1 diabetes mellitus insulin therapy (According to the Moscow segment of the State Register of Diabetes Mellitus)

BACKGROUND: When developing programs for state reimbursement of the cost of medical services and medicines, when providing assistance to patients suffering from type 1 diabetes mellitus (DM1), data based on the results of pharmacoepide-miological studies (FEI) conducted in real clinical practice of treating patients are needed. The obtained results of the analysis of drug consumption allow us to study the most commonly used insulin therapy regimens and their compliance with modern clinical recommendations. Calculations of the weighted average cost of conducting hypoglycemic therapy in DM1 can be used for further pharmacoeconomical calculations, including analysis of the medical and social cost of the disease.AIM: To conduct a pharmacoepidemiological analysis of the consumption of insulin preparations according to the ATX /DDD methodology, to study the modes of insulin administration and the ratio of the weighted average cost of insulin therapy components per 1 patient with DM1 per year in the outpatient practice of treatment with the introduction of insulin in the mode of multiple injections of insulin (MII) and during continuous subcutaneous insulin infusion (CSII).MATERIALS AND METHODS: A retrospective continuous cohort analytical pharmacoepidemiological study was conducted on the basis of the SRDM database (status as of 01/01/2020), in which 17,617 patients with T1DM aged 18 years and older were registered at the time of the study.RESULTS: 90% of patients received analogues of human insulin in the MII mode using syringe pens, 8.6% used the CSII mode. In 34.5% of patients with DM1 HbA1c was <7%, the proportion of patients with HbA1c >8% was 28%. The average cost of insulin therapy per 1 person per year was 54,977 rubles. The cost of basal insulin treatment per 1 patient per year was approximately 1.5 times higher than the cost of bolus insulin during insulin therapy in the MII mode (33,960 rubles and 21,017 rubles, respectively). The weighted average cost of insulin per 1 patient per year for CSII was 31,822 rubles.CONCLUSION: The majority of patients with DM1 in the study cohort received analogues of human insulin in the basic bolus mode of MII using syringe pens, which corresponds to existing clinical recommendations. The proportion of patients achieving the goals of glycemic control is comparable to the data obtained on the basis of registers of diabetic patients in other economically developed countries

Efficacy and safety of different insulin infusion methods in the treatment of total parenteral nutrition-associated hyperglycemia: a systematic review and network meta-analysis.

To systematically evaluate the efficacy and safety of different insulin infusion methods in the treatment of total parenteral nutrition (TPN)-associated hyperglycemia based on published literature and the data of completed clinical trials using a network meta-analysis. A comprehensive search of PubMed, Elsevier, Web of Science, EMBASE, Medline, clinicaltrials.gov, Cochrane Library, and three Chinese databases (Wanfang Data, China National Knowledge Infrastructure, and SINOMED) up to December 15, 2022, was performed to collect information on different insulin infusion methods used for the treatment of TPN-associated hyperglycemia, and the Cochrane systematic review method was used to screen the literature, evaluate the quality of the included literature, and extract clinical characteristics for a network meta-analysis. Clinical outcomes included mean blood glucose (MBG), hypoglycemia, hospital length of stay, hyperglycemia, surgical site infection (SSI) and mean total daily insulin. A total of 21 articles, including 1,459 patients, were included to analyze 6 different routes of insulin infusion, including continuous intravenous insulin infusion (CVII), continuous subcutaneous insulin infusion (CSII), subcutaneous glargine insulin (s.c. GI), the addition of regular insulin to the PN mixture (RI-in-PN), multiple subcutaneous insulin injections (MSII) and 50% of insulin administered as RI-in-PN + 50% of insulin administered as s.c. GI (50% RI-in-PN + 50% s.c. GI). The results of the network meta-analysis showed that MSII was the least effective in terms of MBG, followed by CVII. The 6 interventions were basically equivalent in terms of the hypoglycemia incidence. In terms of the length of hospital stay, patients in the CVII group had the shortest hospital stay, while the MSII group had the longest. CVII was the best intervention in reducing the incidence of hyperglycemia. The incidence of SSI was the lowest in the CSII and CVII groups, and the mean daily insulin dosage was the lowest in the CVII group. Current literature shows that for the treatment of TPN-associated hyperglycemia, CVII is the most effective, reducing the incidence of hyperglycemia and shortening the length of hospital stay without increasing the incidence of hypoglycemia. MSII has the worst efficacy, leading to a higher MBG and longer hospital stay, and RI-in-PN, CSII, s.c. GI and 50% RI-in-PN + 50% s.c. GI are better in terms of efficacy and safety and can be substituted for each other. https://www.crd.york.ac.uk/prospero/, identifier CRD42023439290.

Visually controlled pulsatile release of insulin from chitosan poly-acrylic acid nanobubbles triggered by focused ultrasound

Insulin therapy is the most effective way to control the blood glucose value of diabetic patients. The most effective administration route for insulin is subcutaneous injection because bioavailability for non-injection administration is low and unstable. However, patients often need a multiple daily insulin injection regimen to control basal and postprandial blood glucose, which causes various complications. Controlled pulsatile drug release technology using ultrasound as an external stimulus source is a very promising method to avoid multiple injections of insulin. However, most of the drug-loaded microbubbles used for ultrasound-mediated treatment have a short half-life, which limits their use in controlled pulsatile drug release. More importantly, how to control insulin release is still a challenge. In this paper, chitosan poly-acrylic acid nanobubbles as drug carriers of insulin were prepared to achieve a visually controlled pulsatile release of insulin triggered by focused ultrasound. The experimental results in vivo demonstrated that nanobubbles were stable enough to achieve long-term visualization for 7 days after intramuscular injection in rats. Under the guidance of ultrasound imaging, it is visible to find the position and observe the gray values change of nanobubbles. Thus, when triggered by focused ultrasound, the amount of insulin could be accurately pulsatile released from nanobubbles. In vivo experiments in rats showed that the visually controlled pulsatile release of insulin could be achieved for a long time, up to 3 consecutive days. The blood glucose level could be repeatedly reduced by focused ultrasound irradiation with just one injection. Our research provided a promising way for visually controlled pulsatile release of insulin, which would significantly reduce the injection frequency of insulin.

Switching from Multiple Insulin Injections to a Fixed Combination of Degludec and Liraglutide in Patients with Type 2 Diabetes Mellitus: Results from the Simplify Study After 6Months.

This study aimed to evaluate the effectiveness and safety of switching from basal bolus insulin treatment (BBIT) to a fixed combination of insulin degludec and liraglutide (IDegLira) in patients with type 2 diabetes mellitus (T2DM) who had preserved insulin secretion but inadequate glucose control. The study also aimed to assess the feasibility of implementing this therapeutic approach in common clinical practice settings. This was a non-randomized, open-label, multicenter, prospective, single-arm study involving 234 patients with T2DM who were receiving BBIT. Inclusion criteria were duration of diabetes mellitus > 60months, stable total daily dose of insulin (TDDI) ranging from > 20 to < 70IU/day (approx. > 0.3 to < 0.7IU/kg body weight/day), C-peptide levels > 10% above the lower limit, HbA1c levels > 7% and < 10% (Diabetes Control and Complications Trial), and body mass index > 25kg/m2. The primary endpoints were changes in glycated hemoglobin (HbA1c) and body weight at week 28 after treatment switching. Secondary endpoints included changes in the 7-point glycemic profile, hypoglycemia frequency, blood pressure, blood lipids, liver enzymes, insulin dose, and a patient questionnaire focusing on treatment satisfaction, concerns and impact on daily activities. A subgroup of 55 patients underwent continuous glucose monitoring (CGM) with the evaluation of CGM-derived parameters, such as time in range (TIR), time above range (TAR), time below range (TBR), hypoglycemia, and glucose variability. A significant decrease in HbA1c (8.6% vs. 7.6%; p < 0.0001) and body weight (97.8 vs. 94.0kg; p < 0.0001) was observed at week 28 after treatment switching. Significant improvements were also seen in all measurements of the 7-point glycemic profile (p < 0.0001), reduction in the number of hypoglycemia episodes per patient, and the proportion of patients with at least one hypoglycemia event (p < 0.001). Furthermore, there was a significant decrease in daily insulin dose (55.6 vs. 32.7IU/day; p < 0.0001), as well as improvements in blood pressure, blood lipids, and liver enzymes (gamma glutamyl transferase and alanine aminotransferase). The subgroup of patients who underwent CGM showed a significant increase in TIR (57.9% vs. 69.0%; p < 0.01) and a decrease in TAR (40.1% vs. 28.8%; p < 0.01), while TBR, hypoglycemia (number of episodes per patient and proportion of patients), and glucose variability did not change significantly. The results of this study suggest that switching from BBIT to IDegLira in patients with T2DM and preserved insulin secretion can simplify treatment without compromising glycemic control. The switch to IDegLira was associated with significant improvements in various glucose control parameters, including HbA1c, glycemic profile, hypoglycemia, insulin doses, and CGM-derived parameters TIR and TAR. Additionally, it led to significant reductions in body weight, blood pressure, lipid profile, and liver enzyme levels. Switching to IDegLira may be considered a safe and beneficial approach in clinical practice settings, offering metabolic and individual advantages.

The use of stem cells and 3D bioprinting of pancreatic islets in the treatment of type 1 diabetes mellitus: history and perspectives

Type 1 diabetes mellitus (DM) is a disease characterized by hyperglycemia due to an absolute insulin deficiency caused by autoimmune destruction of insulin-producing β-cells. The disease occurs at a young age, is characterized by a labile course, a tendency to ketoacidosis and leads to the development of vascular complications that contribute to disability and early death of patients. To date, insulin therapy is the only treatment for type 1 diabetes. However, this method of treatment is not perfect. Patients need to adjust their diet, conduct frequent glycemic control and multiple injections of insulin. In this regard, the search for more effective methods of treating type 1 diabetes continues. The transformation of stem cells as a potential source of αand β-cells and their transplantation to the patient seems promising. However, it is not enough to simply obtain α- and β-cells from any stem cell. An important role is played by the interaction between the cells of the pancreatic islets. Currently, attempts are being made to develop functional in vitro models of pancreatic islets in which the cellular microenvironment would be completely preserved. The possibility of culturing and monitoring cells in a permeable three-dimensional microenvironment has been demonstrated. Combining different types of cells with each other in biologically suitable protein hydrogels allows the formation of spatial tissue systems. Cell microvascularization is also important, which is critical for adequate glucose homeostasis. 3D bioprinting can help ensure proper cell distribution in the scaffold and help reduce hypoxia through vascularization. 3D bioprinting technology will solve the problems of creating a natural environment for pancreatic islets with extracellular matrix and vasculature, since this technology will help to create organs in fully controlled conditions in vitro. However, this technology is still developing and further research is required in this direction.

Clinical and HLA genotype analysis of immune checkpoint inhibitor-associated diabetes mellitus: a single-center case series from China.

To investigate the clinical characteristics and HLA genotypes of patients with immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) in China. We enrolled 23 patients with ICI-DM and 51 patients with type 1 diabetes (T1D). Clinical characteristics of the patients were collected. HLA-DRB1, HLA-DQA1, and HLA-DQB1 genotyping was conducted via next-generation sequencing. The ICI-DM patients had a male predominance (70.6%), a mean body mass index (BMI) of 21.2 ± 3.5 kg/m2, and a mean onset of ICI-DM in 5 (IQR, 3-9) cycles after ICI therapy. Most (78.3%) ICI-DM patients were treated with anti-PD-1, 78.3% presented with diabetic ketoacidosis, and all had low C-peptide levels and received multiple insulin injections. Compared to T1D patients, ICI-DM patients were significantly older (57.2 ± 12.4 vs 34.1 ± 15.7 years) and had higher blood glucose but lower HbA1c levels (P<0.05). Only two (8.7%) ICI-DM patients were positive for islet autoantibodies, which was lower than that in T1D patients (66.7%, P<0.001). A total of 59.1% (13/22) of ICI-DM patients were heterozygous for an HLA T1D risk haplotype, and DRB1*0901-DQA1*03-DQB1*0303 (DR9) and DRB1*0405-DQA1*03-DQB1*0401 were the major susceptible haplotypes. Compared to T1D, the susceptible DR3-DQA1*0501-DQB1*0201 (DR3) and DR9 haplotypes were less frequent (17.7% vs 2.3%; P=0.011 and 34.4% vs 15.9%; P=0.025), whereas the protective haplotypes (DRB1*1101-DQA1*05-DQB1*0301 and DRB1*1202-DQA1*0601-DQB1*0301) were more frequent in ICI-DM patients (2.1% vs 13.6%; P=0.006 and 4.2% vs 15.9%; P=0.017). None of the ICI-DM patients had T1D-associated high-risk genotypes DR3/DR3, DR3/DR9, and DR9/DR9. Among the 23 ICI-DM patients, 7 (30.4%) presented with ICI-associated fulminant type 1 diabetes (IFD), and 16 (69.6%) presented with ICI-associated type 1 diabetes (IT1D). Compared to IT1D patients, IFD patients exhibited marked hyperglycemia and low C-peptide and HbA1c levels (P<0.05). Up to 66.7% (4/6) of IFD patients were heterozygous for reported fulminant type 1 diabetes susceptibility HLA haplotypes (DRB1*0405-DQB1*0401 or DRB1*0901-DQB1*0303). ICI-DM shares similar clinical features with T1D, such as acute onset, poor islet function and insulin dependence. However, the lack of islet autoantibodies, the low frequencies of T1D susceptibility and high frequencies of protective HLA haplotypes indicate that ICI-DM represents a new model distinct from classical T1D.

Improvement of mild and more serious hypoglycemia in patients with DM type 1 and type 2 after introduction of Continuous Glucose monitoring in Internal Medicine Residency Clinic

We are describing our experience of introducing Continuous Glucose Monitoring (CGM) for the first time as far as we know not in specialized endocrine clinic, but in Internal Medicine Residency Clinic in USA. The 25- patients we included in the trial were with type 2 Diabetes Mellitus (DM 2) -85% and Type 1 DM (DM1)-15%. They were treated with multiple injections of Insulin per day and were self-Monitoring their blood glucose (SMBG) 4 times a day. Their HbA1c was in the beginning of the trial was 9.5-to 14%. Before the introduction of the CGM the patients were spending 1 hour and 14 minutes a day having mild hypoglycemia- between 69-54 mg/dl-4.75% and more significant hypoglycemia- less than 54 mg/dl 29 min a day-3.01%. The CGM was started in the Clinic by the CGM team. In the CGM team were actively participating a10- Internal medicine and Transitional Year Residents under the supervision of board-Certified Endocrinologist who was a member of the clinic also. The CGM used was Dexcom G6. The goal of the project was to show that not only in specialized centers, but in General Internal Medicine Residency clinic we can not only improve the control of DM type 1 and type 2 in those 25- patients but most importantly reduce the time they had hypoglycemia. The Internal Medicine and Transitional year Residents were actively involved in the project. They were educating the patients before starting the CGM on their die and how to adjust their Insulin at home based on written instruction materials and treat their low blood sugar. The patients were called at least once a week by Internal Medicine Clinic representative of the CGM team with instructions how to adjust their Insulin, treat their hypoglycemia and to counsel them about their diet and physical activity. The patients had scheduled appointment to the clinic once a month. After the glucotoxicity from the initial high blood sugar was overcomed by using the appropriate dose of Insulin the control of the diabetes was achieved with reduction of HbA1c to 7.04% mean from 11.21% before the introduction of the CGM. With the help of the CGM the time spent by the patients with BS less than 70 mg/dl decreased from 1 hour and 14 minutes per day-4.75% to 11 minutes per day-0.78% and the time spend with blood sugar less than 54 mg/dl per day decreased from 29 minutes-3.01% to 3 minute per day-0.25%. Both values after the introduction of CGM were within the American Diabetic Association (ADA) standards- mild hypoglycemia goal of less than 4 % and more significant hypoglycemia goal of less than 1 % per day. Four of the patients were able to have excellent control of their DM 2 without any low blood glucose only on per oral antidiabetic medications and or GLP1-RAG. Our experience showed that introduction of CGM instead of SMBG in General Internal Medicine residency Clinic can help a lot of patients with DM type 1 and type 2 on multiple injections of insulin per day to reduce mild and more serious hypoglycemia and improve their blood sugar control with Insulin. Also, we showed that this can be done safely in General Internal Residency clinic and not only in specialized endocrine clinics which can be adopted in other Internal Medicine residency Clinics in USA. This also significantly improves the education and experience with the CGM devise of our Internal Medicine and Transitional Year Medical Residents.

Improvement of time in range and glucose management indicator in Type 1 and Type 2 Diabetes Mellitus patients after introduction of continuous Glucose monitoring in internal medicine residency clinic

Continuous glucose monitoring (CGM)-derived time in range (TIR) correlates with Glucose management indicator(GMI) which correlates with hemoglobin A1c (HbA1c) among patients with type 1 and type 2 diabetes mellitus. Compare to HbA1c it has better correlation with glucose control, because HbA1c can be influenced by conditions like anemia, Chronic kidney disease, Cirrhosis of the liver etc. With our current project we wanted to introduce CGM not in specialized endocrine clinic, but in Internal medicine Residency clinic. The CGM team had 12 Internal Medicine and Transitional year Residents who were functioning under the supervision of Board Certified Endocrinologist who was a member of the clinic also. Twenty Five patients -85% with type 2 DM and 15% with type 1 DM on multiple injections of Insulin per day-3-4, self-monitored their blood Glucose(SMBG). They were given CGM- Dexcom G6 in the clinic. In the first 2- weeks after the switch the TIR of the blood glucose of the patients-70-180 mg/dl was 18%. Their average blood glucose was 286 mg/dl, GMI was 11.21%. During then first 2- weeks after initiation of CGM the patients were educated in length by our CGM team about their diet, physical activity, how to adjust their Insulin based on their blood glucose levels as well as how to treat the hypoglycemia. Members of the CGM team were contacting the patients twice a week to adjust patients treatment with Insulin and other per oral antidiabetic medications and or injectable – GLP1-RAG if needed after consultation with the Endocrinologist in the clinic based on the shared information between the clinic and the patients. Once a month the patients were seen in the clinic by member of the CGM team as well. The patients were followed for 2- years. After 3- months on CGM and followed for the 2 years thereafter the patients TIR improved from 18 % to 74%, GMI decreased from 11.21% to 7.04% and the average blood glucose decreased from 286 mg/dl to 158 mg/dl. There was also significant reduction of the hypoglycemia. Twenty percent of the patients were able to discontinue their Insulin and be treated only with oral antidiabetic medications plus/minus GLP1-RAG and have GMI less than 7%. We have showed that targeted TIR – above 70% which has been associated recently with diabetic micro and macrovascular complications in diabetic patients can be achieved not only in specialized endocrine clinics , but in Internal Medicine residency clinic and can be adopted by other Internal Medicine Residency programs in USA.

ПОМПОВАЯ ИНСУЛИНОТЕРАПИЯ: ОПЫТ И ПЕРСПЕКТИВЫ ИСПОЛЬЗОВАНИЯ У ДЕТЕЙ С САХАРНЫМ ДИАБЕТОМ 1 ТИПА В АМБУЛАТОРНЫХ УСЛОВИЯХ

The study is based on the results of determining the level of HbA1c and analyzing the medical records of 47 pediatric patients with type 1 diabetes registered with a pediatric endocrinologist, when comparing groups of children on pump insulin therapy and on the regime of multiple daily insulin injections. The results showed that all 100% of patients know the features of the diet in diabetes mellitus, and only 20 patients (42.5%) adhere to the diet strictly. 15 people (83.3%) in the comparison group regularly use the XE system in the main group – 9 people (31%, p &lt; 0.001). A diary of self-control on nutrition and glucose control is regularly kept by 12 people (66.7%) in the main group and 10 patients in the comparison group (34.1%, p = 0.032). The observed averages of HbA1c were comparable in these groups Treatment with multiple insulin injections or continuous subcutaneous insulin infusion had no significant differences among different age groups of children in achieving HbA1c targets on an outpatient basis. In achieving glycemic targets in children and adolescents with T1DM, the constant use of a continuous glucose monitoring system has been proven. The clinical benefit of pump insulin therapy before therapy with multiple daily injections is to reduce the number of episodes of acute complications of T1DM: severe hypoglycemia and diabetic ketoacidosis.

Real-time continuous glucose monitoring: a review

Continuous glucose monitoring (CGM) is preferably recommended for diabetic patients with Type 1, Gestational, and Type 2 diabetes via multiple insulin injections. There is an increasing awareness about its use, even among patients without Diabetes. This review aims to assess the indications, benefits, and future perspectives of CGM. We searched PubMed, MEDLINE, and the first 100 articles in Google Scholar, for articles published in English and assessed the indications, benefits, and recent updates on CGM. The search criteria were limited to articles published from 2013 to November 2022. The keywords such as CGM, indications, benefits, and updates were used. CGM is recommended for use among both types of Diabetes through continuous insulin injections. In addition, CGM is beneficial to patients with gestational diabetes mellitus and patients that experience frequent hypoglycemic attacks. Although CGM is imperative for diabetic patients, the cost is a major limiting factor. There is an increasing awareness about the use of CGM among patients without Diabetes to avoid Diabetes, improve life quality, and enhance mental and physical health. The effects of CGM on HbA1c might be conflicting. However, it improved time in the range, microvascular complications, and fetus and mother complications.

Взаимосвязь показателей вариабельности гликемии и нарушений сердечного ритма у пациентов с сахарным диабетом 1 типа

Objective: To study indicators of glycemic variability (GV) and their relationship with cardiac arrhythmias in patients with type 1 diabetes mellitus according to glucocardiomonitoring data. Design: Cross-sectional study. Materials and methods. The study included 72 patients with type 1 diabetes without previously diagnosed cardiovascular pathology. Of these, 34 patients received insulin pump therapy, 38 received multiple insulin injections. The average age of patients was 39.7 ± 15.9 years, the average duration of type 1 diabetes was 15.4 ± 10.8 years. The level of glycated hemoglobin (HbA1c) was determined in patients, and according to continuous glucose monitoring (CGM), GV indices were calculated: SD (standard deviation), CONGA (continuous overall net glycemic action), LI (lability index), MAGE (mean amplitude of glycemic excursions), MAG (mean absolute glucose). Simultaneously with CGM, Holter monitoring of the electrocardiogram was carried out: heart rate (HR), the presence and time of occurrence of arrhythmias, variability of the corrected QT interval (QTc), and the presence of ischemic changes were assessed. A correlation analysis of the relationships between GV levels and heart rhythm disorders was carried out. Results. Regardless of the type of insulin therapy, GV indicators in patients with type 1 diabetes were higher than the reference values for healthy individuals. Only 19 (26%) patients reached the target HbA1c level. In 62 (86%) people, various heart rhythm disturbances were registered, in 30 (42%) of patients there was a decrease in the circadian index (CI) of heart rate, and in 14 (19%) there was a prolongation of the QTc interval. The results of the correlation analysis showed that with an increase in GV, the HR CI decreased and the frequency of supraventricular and ventricular extrasystoles increased. Conclusion. The detected changes in heart rhythm against the background of increased GV in patients with type 1 diabetes indicate a high risk of developing a cardiovascular process. Strict glycemic control and normalization of GV can better reduce the risk of cardiac arrhythmia and the development of DCAN in patients with type 1 diabetes. Keywords: type 1 diabetes mellitus, glycemic variability, cardiovascular disease, diabetic cardiovascular autonomic neuropathy

Diabetes Control in the Community, Under the Management of a Diabetes-Clinic Nurse Specialist, and the Effect of a Parallel Diabetologist Advice.

Nurses play a key role in managing care and educating people with diabetes in various healthcare systems worldwide, while physicians play this role in others. In addition, some healthcare systems authorize specialist nurses to change patient dose regimens. Therefore, we examined diabetes outcomes in the community by the management of a diabetes-clinic nurse only versus parallel management with a diabetologist. Retrospective data were collected for 100 consecutive people with diabetes registered in a community clinic with a diabetes-clinic nurse specialist as a case manager from 1/2018. About half of the patients selected received parallel advice from a diabetologist. Inclusion criteria included poor control of type 2 diabetes (HbA1c above 9%). Patients using an insulin pump, glucose sensor technologies, or multiple injection insulin programs were excluded. One hundred people with diabetes who met the study criteria were included in the study, 64 males and a mean age of 60.03 ± 11.11. In a follow-up of 161.31 ± 68.65 days, HbA1c levels decreased by 3.17% ± 1.95% and did not change in a further follow-up of 162.36 ± 72.75 days. Significant improvement was also observed in controlling the other risk factors examined. Parallel consultation with a diabetologist and the nurse's use of her authority for dose modifications showed no differences in all parameters. Logistic regression for analyzing the effect of the variables related to the patient showed only a moderate effect. Access to professional services remains a significant challenge for healthcare systems in long-term diabetes control. Monitoring poorly controlled people with diabetes with the help of a diabetes-clinic nurse specialist in the community clinic significantly improved diabetes and risk factors control and persisted long after the intervention. Healthcare systems should consider expanding the service of the diabetes-clinic nurse specialist in the community. Further studies will be required to examine the results in different patient subgroups.

Case report about treatment of the patient with DM Type 2 on multiple injections of insulin who with the help of continuous glucose monitoring (CGM) improved and was controlled only on anti-diabetic pills and GLP1 - RAG

We would like to describe a patient who was treated for decompensated Diabetes Mellitus Type 2(DM type 2) with Multiple Injections of Insulin per day. His HbA1c while when he visited our clinic was above 14 %. He was self-monitoring his Blood sugar at home (SMBG) 4- times a day. He was treated only with Metformin ER in the past. The CGM was started in Internal Medicine Residency Clinic. The patient start sharing his CGM data with the clinic through Dexcom G6 CGM and compatible I phone. The patient was educated on diet, how to adjust his insulin at home based on written instruction material. Moreover, the patient was called at least once a week by the Medicine Clinic professional how to adjust his insulin and to counsel him about his diet and physical activity. The patient had scheduled appointment to the clinic at least once a month. After the glucotoxicity from the initial high blood sugar was managed by using the appropriate dose of insulin, the insulin dosages started to decrease in our patient. DM type 2 was well controlled with GMI less than 7% after starting the CGM. During the clinic visits, the morning fasting C- peptide of the patient was increased which we attribute due to his morbid obesity. These gave us the opportunity to start the patients on per oral antidiabetic medications and injectable GLP-1 receptor agonists (GLP-1-RAG). The patient’s DM type 2 control was maintained 3-6 months after stopping the insulin with Glucose management index (GMI) which approximates HbA1c less than 7%. Our experience with this patient showed that introduction of CGM instead of SMBG in the General Internal Medicine Residency Clinic can help patients with DM type 2 to improve their blood sugar control with Insulin and eventually stop the Insulin and start therapy with oral antidiabetic agents and or injectable GLP-1 -RAG. Also, we showed that this can be done safely in General Internal Medicine Residency clinic and not only in specialized clinics.