Cost-effectiveness of insulin degludec/insulin aspart versus biphasic insulin aspart in Chinese population with type 2 diabetes.

Objective: To evaluate the long-term cost effectiveness of insulin degludec/insulin aspart (IDegAsp) vs. biphasic insulin aspart 30 (BIAsp 30) for the treatment of people with type 2 diabetes mellitus (T2DM) inadequately managed on basal insulin in China. Methods: The CORE (the Center for Outcomes Research) Diabetes Model, which has been published and verified, was used to simulate disease progression and calculate the total direct medical costs, life years (LYs) and quality-adjusted life years (QALYs) over 30 years, from the perspective of Chinese healthcare system. The patient demographic information and clinical data needed for the model were gathered from a phase III treat-to-target clinical trial (NCT02762578) and other Chinese cohort studies. Medical costs on treating diabetes were calculated based on clinical trial and local sources. The diabetes management and complications costs were derived from published literature. A discounting rate of 5% was applied to both health and cost outcomes. And one-way and probabilistic sensitivity analyses were carried out to test the reliability of the results. Results: Compared with BIAsp 30, treatment with IDegAsp was associated with an incremental benefit of 0.001 LYs (12.439 vs. 12.438) and 0.280 QALYs (9.522 vs. 9.242) over a 30-year time horizon, and increased CNY (Chinese Yuan) 3,888 (390,152 vs. 386,264) for total costs. IDegAsp was cost-effective vs. BIAsp 30 therapy with an incremental cost-effectiveness ratio of CNY 13,886 per QALY gained. Results were robust across a range of sensitivity analyses. Conclusion: Compared with BIAsp 30, IDegAsp was a cost-effective treatment option for people with T2DM with inadequate glycemic management on basal insulin in China.

Impact of empagliflozin add-on therapy on quality of life in patients of type 2 diabetes mellitus with hypertension: A prospective study.

Background: Diabetes has a negative impact on patient's quality of life (QoL). Comorbidities and polypharmacy further worsen their QoL. Thus, in addition to glycemic control, assessment of QoL is also gaining importance. Objective: The objective of this study was to evaluate QoL in patients of type 2 diabetes mellitus (T2DM) with hypertension after add-on empagliflozin to triple drug therapy (metformin, teneligliptin, and glimepiride). Materials and Methods: A prospective research was done on T2DM patients with hypertension, who visited a tertiary care referral institute's endocrine outpatient clinic. For 3 months, empagliflozin, 25 mg once daily, was administered as an add-on treatment with metformin, teneligliptin, and glimepiride. In addition to clinical assessment, an Urdu-translated QoL instrument for Indian diabetes patients was used to conduct QoL study. The QoL outcomes prior to empagliflozin add-on were compared with those obtained at the conclusion of the 3 months of treatment. Results: Empagliflozin as an add-on therapy significantly improved various aspects of QoL like role limitation due to physical health, physical endurance, general health, symptom botherness, financial worries, emotional/mental health, and diet satisfaction (P < 0.001). It also improved glycemic and blood pressure parameters significantly. Conclusion: QoL is an essential measure with respect to patient-centered treatment approach. Empagliflozin, as an add-on medication, improved QoL, glycemic parameters and blood pressure in T2DM patients with hypertension. It can be recommended as an add-on, but more research with a larger sample size is required.

[Relationship of carbohydrate metabolism indicators during adjuvant radiotherapy and survival in patients with glioblastoma]. / Vzaimosvyaz' pokazatelei uglevodnogo obmena v period provedeniya ad"yuvantnoi luchevoi terapii i vyzhivaemosti u patsientov s glioblastomoi golovnogo mozga.

Despite the improvement of treatment methods, survival of patients with glioblastoma is still low. Glioblastoma is the most common brain tumor. OBJECTIVE: To study carbohydrate metabolism in patients with glioblastoma during adjuvant external beam radiation therapy and its impact on survival. MATERIAL AND METHODS: The study included 66 patients with glioblastoma (Karnofsky score ≥80%) who underwent hypofractionated adjuvant external beam radiation therapy (single focal dose 2.5-3Gr). Patients received dexamethasone 4-8 mg daily throughout the entire course of irradiation. RESULTS: High level of glycated hemoglobin (HbA1c) was observed in 33.3% of patients with glioblastoma undergoing irradiation. Cumulative survival was 17 months (95% CI 13.7-20.3). Two indicators had a significant negative impact on cumulative survival: age of patients (HR 1.04; 95% CI 1.01-1.08; p=0.02) and level of HbA1c (HR 1.94; 95% CI 1.23-3.06; p=0.005). Cumulative survival was significantly (p=0.022) higher in patients younger 53 years compared to older people (18 months and 14 months, respectively). Cumulative survival was 20 months among patients whose HbA1c did not exceed the upper reference value (<5.8%). Survival was higher (p=0.017) in these ones compared to patients with HbA1c ≥5.8% (13 months). According to multivariate Cox regression model, high HbA1c was the only significant negative predictor of cumulative survival (HR 3.35; 95% CI 1.14-9.81; p=0.027). CONCLUSION: High HbA1c is unfavorable predictor of cumulative survival in patients with glioblastoma and Karnofski score ≥80% undergoing adjuvant hypofractionated irradiation regardless their age.

Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial.

Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P < 0.025). At week 13, the placebo-corrected reduction in HbA1c percentage was -0.53 (95% CI -0.89 to -0.17, nominal P = 0.004) in the 35 mg volagidemab group and -0.49 (95% CI -0.85 to -0.12, nominal P = 0.010) in the 70 mg volagidemab group. No increase in hypoglycemia was observed with volagidemab therapy; however, increases in serum transaminases, low-density lipoprotein (LDL)-cholesterol and blood pressure were observed. Although the primary endpoint did not meet the prespecified significance level, we believe that the observed reduction in HbA1c and tolerable safety profile provide a rationale for further randomized studies to define the long-term efficacy and safety of volagidemab in patients with T1D.

COVID-19 and diabetic ketoacidosis: A case series at an urban district hospital in South Africa.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with an increased prevalence and mortality from diabetic ketoacidosis (DKA) globally. With limited access to specialised care, most patients with DKA in South Africa are managed at district hospital level. This study describes the profile of patients admitted to a district hospital in South Africa with DKA and COVID-19 and examines associated risk factors encountered. METHODS: This was a case series of all patients presenting to a district hospital with DKA and COVID-19 infection between July 2020 and July 2021. Data extracted included patients' demographic profiles, biochemical results, comorbidities and clinical outcomes. RESULTS: The median age of the 10 patients admitted during the study period was 39 years old (±12), six of whom were male. The hemoglobin A1c (HbA1c) values on admission ranged from 9.7 to 13.8. Five of the patients had pre-existing type 2 diabetes mellitus (DM). Four of the known DM patients were on metformin only, and one was on biphasic insulin. Three patients had other pre-existing comorbidities, two patients with hypertension and one with human immunodeficiency virus (HIV). Three patients demised, two of whom were hypoxic on admission. CONCLUSION: Diabetic ketoacidosis appears more commonly in COVID-19 infected patients with type 2 DM and at a young age. Suboptimal glycaemic control was associated with DKA, and hypoxia was a strong predictor for mortality. Treatment inertia was evident in the known DM group, who were on monotherapy despite persistent hyperglycaemia. Greater vigilance is required to detect ketosis in type 2 DM and intensify therapy to improve glycaemic control.

[Comparison of the efficacy of PCSK9 inhibitors and statins on dyslipidemia in patients with type 2 diabetes].

Objective: To compare the efficacy of preprotein convertase subtilisin lysozyme 9 (PCSK9) inhibitors with statins in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 140 patients with T2DM (80 males and 60 females) in the People's Hospital Affiliated to Shandong First Medical University from January 2018 to January 2021 were selected, with a mean age of (55±5) years (41-72 years). The patients were divided into observation group (n=68) and control group (n=72) by the random number table method. Both groups were given conventional treatments such as hypoglycemic drugs, the control group was given statins to regulate lipids, and the observation group was given PCSK9 inhibitors to lower lipids. The differences of low-density lipoprotein cholesterol (LDL-C), interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) expression levels and standard-reaching rate of LDL-C between the two groups were compared. The correlation between serum PCSK9 level and fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and other indicators in T2DM patients was analyzed by Pearson correlation analysis. Results: After treatment, the LDL-C of the observation group was (2.3±0.7) mmol/L, which was lower than that of the control group [(2.7±0.7) mmol/L] (P=0.024); the standard-reaching rate of LDL-C of the observation group was 89.7% (61/68), which was higher than that of the control group [68.1% (49/72)] (P=0.002); the levels of IL-1, IL-6, TNF-, CRP, IL-10 and IL-8 in the observation group after treatment were (27.6±6.6) ng/L, (36.7±6.9) ng/L, (40.1±8.9) ng/L, (7.8±1.8) ng/L, (19.2±3.3) ng/L, (13.7±3.3) ng/L, respectively, which were lower than those in the control group [(30.6±7.9) ng/L, (40.1±7.3) ng/L, (43.4±9.2) ng/L, (10.4±2.5) ng/L, (30.7±3.7) ng/L, (26.8±3.4) ng/L, respectively] (all P<0.05). After treatment, the PCSK9 level in the observation group was (74±13) µg/L, which was lower than that in the control group [(97±14) µg/L] (P<0.001). The level of PCSK9 in T2DM patients was positively correlated with LDL-C, IL-1, IL-6 and TNF-α (r=0.390, 0.433, 0.398 and 0.562, all P<0.05). Conclusion: PCSK9 inhibitors have better lipid-regulating effects in patients with T2DM and can improve the level of inflammation at the same time.

[Type 2 diabetes. Is it possible to achieve the glycemic goal in real life?] / Diabetes Tipo 2 ¿en la vida real es posible lograr la meta glucémica?

INTRODUCTION: Achieving glycemic control in type 2 diabetes(T2D) prevents or delays chronic complications and extends survival. AIM: to analyze metabolic control goals in adults with T2DM, treated by specialists in their usual practice in Argentina, and their relationship with adherence to prescribed medications, different treatment strategies, time of diagnosis, quality of life variables and presence of chronic complications of T2DM. METHODS: cross-sectional design; multicenter study conducted in 28 centers in Argentina during 2018. The sample was selected randomly and systematically. Morisky-Green-Levine and WHO-5 adherence questionnaire for quality of life was applied. History of disease and laboratory markers were analyzed. RESULTS: of 1329 DMT2 cases included, 60.2% achieved the goal. Regarding pharmacological treatment in diabetes: 5.1% were without medication, 47.5% with 1 drug, 34.5% with 2, 12.9% with 3 or more; in turn, with insulin (alone or combined) 38.1%. According to the questionnaire, 68.4% adhered to treatment and 72.6% reached A1C <7%. Among the non-adherents, 27.4% reached the goal. Achieving the glycemic goal was associated with age = 65 years (p < 0.0001), higher adherence score (p < 0.0001), private health insurance (p < 0.0001), and physical activity (p < 0.02). The worst metabolic control was associated with time of DMT2 diagnosis (p <0.0001), insulin therapy (p < 0.0001) and symptoms of depression (p < 0.002) Conclusions: The youngest and most vulnerable presented lower values for adherence; intervening and intensifying the treatment earlier in them would allow better results.

Lograr control glucémico en diabetes tipo 2 (DMT2) previene, o enlentece las complicaciones crónicas y prolonga la supervivencia. Objetivo: analizar metas de control metabólico en adultos con DMT2 tratados por especialistas en Argentina y su relación con la adherencia a la medicación prescrita, las diferentes estrategias de tratamiento, la antigüedad de la enfermedad, las variables de calidad de vida y presencia de complicaciones crónicas de DMT2. Métodos: diseño transversal; estudio multicéntrico realizado en 28 centros de Argentina durante 2018. La muestra se seleccionó en forma aleatoria y sistemática. Se aplicó cuestionario de adherencia Morisky-Green-Levine y OMS-5 para calidad de vida. Se analizaron antecedentes de enfermedad y marcadores de laboratorio. Resultados: de 1329 casos de DMT2 incluidos, el 60.2% logró la meta. Respecto al tratamiento farmacológico en diabetes: el 5.1% estaba sin medicación, 47.5% con 1 fármaco, el 34.5% con 2, el 12.9% con 3 o más; a su vez, con insulina (sola o combinada) el 38.1%. Según cuestionario, adhería al tratamiento el 68.4% y el 72.6% alcanzó A1C < 7%. Entre los no adherentes, alcanzó la meta glucémica el 27.4%. Lograr esta meta se asoció con edad mayor de 65 años (p < 0.0001), mayor score de adherencia (p < 0.0001), tener medicina prepaga (p < 0.0001), y realizar actividad física (p < 0.02). El peor control metabólico se asoció con antigüedad de DMT2 (p < 0.0001), insulinoterapia (p < 0.0001) y síntomas de depresión (p < 0.002) Conclusiones: Los más jóvenes y los más vulnerables presentaron menor adherencia; en ellos intervenir e intensificar tratamiento más tempranamente permitiría mejores resultados.

Comparing the effectiveness of continuous subcutaneous insulin infusion with multiple daily insulin injection for patients with type 1 diabetes mellitus evaluated by retrospective continuous glucose monitoring: A real-world data analysis.

Objective: Regarding the effects and practical application of insulin pumps on patients with type 1 diabetes mellitus (T1DM), the real-world evidence is limited especially concerning the incidence of hypoglycemia. This study aimed to compare the efficacy of continuous subcutaneous insulin infusion (CSII) therapy with multiple daily injection (MDI) therapy on glycemic metrics evaluated by retrospective continuous glucose monitoring (CGM) in Chinese patients with T1DM. Methods: In total, 362 T1DM Chinese patients from the outpatient department of the Second Xiangya Hospital, Central South University, who underwent intensive insulin therapy and used a retrospective CGM system were included in this retrospective cross-sectional study. Comprehensive analysis of clinical and biological features and retrospective CGM derived-metrics was performed on the 362 enrolled T1DM patients who underwent CSII (n = 61) or MDI (n = 301) therapy (defined as 4 or more insulin injections per day). Results: Our findings demonstrated that patients who underwent CSII therapy, compared with those who received MDI therapy, had lower levels of hemoglobin A1c (HbA1c) and fasting blood glucose; moreover, CSII therapy was associated with better glycemic outcomes in terms of increasing time in range (TIR), decreasing time above range (TAR), and achieving CGM-associated targets of TIR ≥70% and TAR <25%. However, patients who underwent CSII therapy did not experience decreasing time below range (TBR), achieving CGM-associated targets of TBR <4%, and reduction of the risk of hypoglycemia as evidenced by comparing TBR and low blood glucose index (LBGI) between the two treatment regimens. The parameters of glycemic variability, such as standard deviation of glucose (SD), mean amplitude glycemic excursion (MAGE), and large amplitude glycemic excursion (LAGE) in T1DM patients who underwent CSII therapy outperformed. Conclusion: Our results provided further evidence that CSII therapy is safe and effective for management of Chinese T1DM patients, which was confirmed by a lower HbA1c level and better CGM-derived metrics but no demonstration of improvment in the risk of hypoglycemia. To achieve more satisfactory glycemic outcomes through the utilization of CSII therapy for Chinese T1DM patients, a strong physician-patient relationship is essential.

Metformin with Versus without Concomitant Probiotic Therapy in Newly Diagnosed Patients with Type 2 Diabetes or Prediabetes: A Comparative Analysis in Relation to Glycemic Control, Gastrointestinal Side Effects, and Treatment Compliance.

BACKGROUND: To evaluate the impact of concomitant use of probiotic BB-12 in metformin-treated patients with type 2 diabetes or prediabetes on glycemic control, metformin-related gastrointestinal side effects, and treatment compliance. METHODS: A total of 156 patients (mean [standard deviation] age: 50.9 [9.9 years], 74.4% females) with newly diagnosed type 2 diabetes or prediabetes were randomly assigned to receive either metformin alone (n = 84, MET group) or metformin plus Bifidobacterium animalis subsp. lactis (BB-12) probiotic (n = 72, MET-PRO group). Data on body mass index (kg/m2), fasting blood glucose (mg/dL), blood lipids, and glycated hemoglobin (HbA1c) levels were recorded at baseline and at the third month of therapy. Data on gastrointestinal intolerance symptoms and treatment noncompliance were also recorded during post-treatment week 1 to week 4. RESULTS: MET-PRO versus MET therapy was associated with a significantly higher rate of treatment compliance (91.7% vs 71.4%, P = .001), greater reduction from baseline HbA1c values (0.9 [0.4-1.6] vs 0.4 [0-1.6] %, P < .001) and lower likelihood of gastrointestinal intolerance symptoms, including abdominal pain (P = .031 to <.001), diarrhea (P = .005 to <.001) and bloating (P = .010 to <.001). Noncompliance developed later (at least 15 days after the therapy) in a significantly higher percentage of patients in the MET group (P = .001 for 15-21 days and P = .002 for 22-28 days). CONCLUSION: In conclusion, the present study proposes the benefit of combining probiotics with metformin in the treatment of patients with T2D or prediabetes in terms of improved glycemic control and treatment adherence rather than correction of dyslipidemia or weight reduction.

The use of metformin for type 2 diabetes prevention: Observational multicenter study from Saudi Arabia.

Background: Patients with prediabetes are at higher risk of developing type 2 diabetes. While intensive lifestyle modification is the primary approach to delaying diabetes, metformin has been shown to be effective, especially among patients younger than 60 years and obese (body mass index (BMI) > 35 kg/m2), patients with fasting blood glucose ≥ 6.1 mmol/L or HbA1c ≥ 6%, and women with history of gestational diabetes. Thus, metformin is now recommended as an option for diabetes prevention by the American Diabetes Association (ADA). The use of metformin among patients with prediabetes in Saudi Arabia and their adherence to the guideline's recommendation for the prevention of type 2 diabetes is unknown. This study aimed to identify the prevalence of metformin use among prediabetes patients overall and patients who are more likely to benefit from metformin use per the ADA guidelines. Methods: A retrospective cohort study was conducted encompassing data from three tertiary care hospitals between January 2015 and June 2019. All patients aged 20 to 70 years with prediabetes (HbA1c of 5.7-6.4%) were included, while patients with an established diagnosis of diabetes, creatinine clearance <45 ml/min, using antihyperglycemic medications other than metformin, or on metformin for other indications were excluded. Prediabetes patients who are most likely to benefit from metformin for type 2 diabetes prevention are those younger than 60 years with a BMI ≥ 35 kg/m2, patients with fasting blood glucose ≥ 6.1 mmol/L or HbA1c ≥ 6%, and women with history of gestational diabetes. This study examined the prevalence of metformin use among all patients with prediabetes, as well as patients who would be more likely to benefit from metformin use per the ADA guidelines. Results: A total of 251 patients were included in this study; 52.2% were female, with a mean age of 47.0 (11.9) years and BMI of 32.3 (6.5) kg/m2, and the median HbA1c at baseline was 5.8% (5.7-6.0). Among the overall sample, 18 patients (7.2%) received metformin for the prevention of type 2 diabetes, 14 of those were from the groups that are more likely to benefit from metformin use per the ADA guidelines (9.9%). Conclusions: Among individuals with prediabetes in Saudi Arabia, metformin use was very low despite the evidence supporting its safety, convenience, and efficacy. Healthcare providers seemed hesitant to medicalize prediabetes; furthermore, the low use of metformin suggests the existence of several barriers that need to be identified and resolved. Increasing providers' knowledge and awareness regarding screening and management of prediabetes is highly encouraged.

Efficacy of Yishen Huashi Granules Combined with Linagliptin Tablets on Blood Glucose and Renal Function in Patients with Type 2 Diabetic Nephropathy.

Objective: To probe into the efficacy of Yishen Huashi granules combined with linagliptin tablets in the treatment of type 2 diabetic nephropathy (DN) and its effect on blood glucose and renal function in patients. Methods: 70 patients with type 2 DN at our hospital between May 2020 and May 2022 were chosen as the research objects and separated into the control group and the research group based on their treatments. With 35 cases in each group, the patients treated with initial therapy and linagliptin tablets were enrolled in the control group, and those who received the above treatments and also Yishen Huashi granules were included in the research group. Their clinical indexes such as blood glucose and renal function were compared with both groups after treatment. Results: After treatment, the research group had remarkably lower fasting blood glucose (FPG), 2 h-postprandial blood glucose (2 h-PBG), and glycosylated hemoglobin A1c (HbA1c) levels than those in the control group (P < 0.05). After treatment, the research group had remarkably lower levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) (P < 0.05) and higher high-density lipoprotein (HDL) levels (P < 0.05) than those in the control group. After treatment, the urinary microalbumin (u-mALB) level was remarkably lower in both groups (P < 0.05) and was distinctly lower in the research group than in the control group (P < 0.05). After treatment, the research group had remarkably lower renal function indexes such as serum creatinine (SCr), blood urea nitrogen (BUN), urinary protein (UPro), and urinary albumin excretion rate (UAER) (P < 0.05) and a higher estimated glomerular filtration rate (eGFR) level (P < 0.05) than those in the control group. The efficacy was evaluated by the traditional Chinese medicine (TCM) syndrome score after treatment. There were no patients in complete remission between both the groups, where slight differences were found in the proportion of significant remission (P > 0.05), with the total effective rate of the research group remarkably higher than that of the control group (P < 0.05). Conclusion: The combination of Yishen Huashi granules and linagliptin tablets can reduce the blood glucose and blood lipid levels in patients with type 2 DN and lower UPro and protect renal function at the same time, which provides a new idea and a method for clinical treatment of type 2 DN with integrated traditional Chinese and Western medicine.

DKA Prevention and Insulin Pumps: Lessons Learned From a Large Pediatric Pump Practice.

PURPOSE: This purpose of the study was to describe recent diabetic ketoacidosis (DKA) incidence data in youth with type 1 diabetes using insulin pumps and the impact of continuous glucose monitors (CGMs) on DKA rates. METHODS: DKA data were obtained through a retrospective chart review of insulin pump users (ages <26 years) between December 2019 and June 2021 in an academic pediatric endocrinology practice where 68% of patients were pump users. RESULTS: Among 591 pump patients, 28 events occurred (3.16 events per 100 patient-years). Mean age was 13.6±3.4 years; 85.7% ranged from 12 to 19 years. Mean A1C was 10.2±2.3%, diabetes duration was 6.1±4.0 years, and 57.1% used CGM. Admission pH levels ranged between 7.0 and 7.31, with 28.6% of events classified as "moderate" and 46.4% "severe." There was no significant difference in the DKA severity between those who wore a CGM and those who did not (ie, pH, serum bicarbonate, mentation alteration, length of stay, intensive care unit admission, and hospital admission). DKA events were attributed to concurrent illness (10.7%), insulin omission (14.3%), pump site failure (57.1%), or other pump malfunctions (14.3%). CONCLUSION: DKA events in pump-treated patients were relatively uncommon; most episodes occurred in adolescents with higher A1C levels, and notably, most events could have been avoided if users followed standard troubleshooting guidelines. Thus, DKA prevention education should be reinforced at each encounter, particularly for teens with higher A1C levels. Moreover, more than 50% of those with DKA episodes wore a CGM, suggesting that pump users using CGM require frequent reinforcement of this education and that the development of such educational materials is critical.

Comparison of Intensive Insulin Versus Oral Regimens on Early Glycemic Control Following Kidney Transplant.

Introduction: Insulin is commonly prescribed to manage early post-kidney transplant hyperglycemia due to its flexibility. Studies comparing the effectiveness of oral therapies on glycemic outcomes remain limited. Project aims: The purpose of this program evaluation was to analyze our experience using oral antiglycemic agents immediately post-kidney transplant, compared to patients managed with insulin monotherapy. Design: This was a single-center, retrospective review of adult kidney transplant recipients with new or worsening hyperglycemia between 01/2014-05/2020. Patients were excluded if they had a prior or combined organ transplant, type 1 diabetes, or were previously on intensive insulin. Patients discharged on oral medications were 1:1 matched to patients receiving intensive insulin based on pre-specified clinical parameters. The primary endpoint was the number of diabetes-related readmissions within 6-months of transplant. Key secondary endpoints included mean serum glucose and hemoglobin A1c levels. Results: Thirty patients prescribed oral therapies were successfully matched to patients receiving intensive insulin. Baseline characteristics were similar between groups, except for more whites in the insulin group. There were no differences in diabetes-related (6.7% vs 3.3%; P = 1.00) or all-cause readmissions within 6-months. Mean serum glucose (P = .99) and hemoglobin A1c (P = .49) levels were also similar between patients receiving oral agents and insulin. However, 7 patients in the oral group were eventually converted to standing insulin. Conclusion: Our experience suggested that the early use of oral antiglycemics post-kidney transplant in select patients can result in similar outcomes relative to insulin. Meticulous follow-up is necessary as one-quarter of patients may require conversion to insulin within 1-month.

Immunogenicity, Efficacy, and Safety of Biosimilar Insulin Aspart (MYL-1601D) Compared with Originator Insulin Aspart (Novolog®) in Patients with Type 1 Diabetes After 24 Weeks: A Randomized Open-Label Study.

BACKGROUND: MYL-1601D is a proposed biosimilar of originator insulin aspart, Novolog®/NovoRapid® (Ref-InsAsp-US/Ref-InsAsp-EU). OBJECTIVE: This study assessed the immunogenicity, efficacy, and safety of MYL-1601D with Ref-InsAsp-US in patients with type 1 diabetes mellitus (T1D). METHODS: This was a 24-week, open-label, randomized, phase III study. Patients were randomized 1:1 to mealtime MYL-1601D or Ref-InsAsp-US in combination with insulin glargine (Lantus SoloSTAR®) once daily. The treatment-emergent antibody response (TEAR) rate (defined as patients who were anti-insulin antibody [AIA] negative at baseline and became positive at any timepoint post-baseline or patients who were AIA positive at baseline and demonstrated a 4-fold increase in titer values at any timepoint post-baseline) was the primary endpoint. The study also compared the change from baseline in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), prandial, basal, and total daily insulin, 7-point self-monitored blood glucose (SMBG) profiles, immunogenicity, and adverse events (AEs) including hypoglycemia. RESULTS: In total, 478 patients were included in the intent-to-treat analysis (MYL-1601D: 238; Ref-InsAsp-US: 240) set. The 90% confidence interval (CI) for the primary endpoint was within the pre-defined equivalence margin of ±11.7% and the treatment differences (SE) in TEAR responders between the treatment groups was - 2.86 (4.16) with 90% CI - 9.71 to 3.99. The mean (SD) changes from baseline for HbA1c, FPG, and insulin dosages were similar in both groups at week 24. The safety profiles including hypoglycemia, immune-related events, AEs, and other reported variables were similar between the treatment groups at week 24. CONCLUSIONS: MYL-1601D demonstrated similar immunogenicity, efficacy, and safety profiles to Ref-InsAsp-US in patients with T1D over 24 weeks. CLINICAL TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03760068.

Exercise-Diet Therapy Combined with Insulin Aspart Injection for the Treatment of Gestational Diabetes Mellitus: A Study on Clinical Effect and Its Impact.

Objective: To explore the clinical effect and impact of exercise-diet therapy combined with Insulin Aspart Injection on gestational diabetes mellitus (GDM). Methods: The objects of study were patients with pregestational diabetes mellitus (PGDM) and 62 patients with GDM who were diagnosed by oral glucose tolerance test (OGTT) and insulin release test from February 2017 to February 2019. According to the severity of the disease, enrolled patients were informed to have appropriate exercise and diet control or Insulin Aspart Injection on this basis until the completion of delivery. By using 50 pregnant women with normal glucose as the control, the fasting plasma glucose (FPG), 1-hour postprandial glucose (1hPG), 2-hour postprandial glucose (2hPG), nocturnal glucose, and glycosylated hemoglobin (HbA1c) levels were compared between the PGDM group and the GDM group before and after treatment; besides, further comparison was made in terms of glucose compliance rate, islet B-cell secretory function, and insulin resistance after treatment. The pregnant women were examined by B-ultrasound at 24 and 26 weeks of gestation to check if the fetus had abnormalities in the central nervous system and the heart. Further B-ultrasound examination was performed at 32 and 37 weeks of gestation to check the problems such as polyhydramnios and stillbirth. In addition, a comparative analysis was carried out in terms of the adverse pregnancy outcomes and complications, associated with the comparison of the results after treatment with control group. Results: After treatment, the levels of FPG, 1hPG, 2hPG, nocturnal glucose, and HbA1c were decreased in the PGDM group and GDM group than those before treatment, especially in the GDM group, with significant difference still when compared with the control group (P < 0.05). Statistical analysis revealed that the blood glucose compliance rate in the GDM group was higher than that in the PGDM group, showing a better therapeutic effect. Fasting insulin (FINS) and homeostasis model assessment index for insulin resistance (HOMA-IR) in the GDM group were significantly higher than those in control group, but lower than those in the PGDM group (P < 0.01), while the level of HOMA-ß was lower in the GDM group than that in the control group and higher than that in PGDM (P < 0.01). Further ultrasound examination revealed the presence of fetal cardiac abnormality, polyhydramnios, stillbirth, and problems, showing a higher incidence in the PGDM group but almost nonexistence in the control group. In addition, the incidence of hypertension, macrosomia, premature rupture of membranes, postpartum hemorrhage, and infection were obviously higher in the PGDM group than those in the GDM group and control group (P < 0.05). Conclusion: Exercise-diet therapy combined with Insulin Aspart Injection can effectively control the blood glucose level of pregnant patients with GDM, improve the pregnancy outcome to a certain extent, and ensure the health of pregnant women and fetus, which is worthy of clinical application.

Single-center Evaluation of Safety & Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Solid Organ Transplantation.

Introduction: Given the negative outcomes associated with uncontrolled diabetes mellitus, non-insulin therapies with glycemic, cardiovascular, and weight-loss benefits in the general population, such as the glucagonlike peptide-1 receptor agonists (GLP1-RA) have become a more alluring therapeutic option in transplant populations. However, limited evidence exists to demonstrate its safety and efficacy in solid organ transplant. Methods: This program evaluation included adult kidney, liver, lung transplant recipients initiated on a GLP1-RA for diabetes mellitus management for a minimum of 3 months, had at least one follow-up visit after starting therapy, and had at least one hemoglobin A1c (HbA1c) level drawn between 3-12 months after GLP1-RA initiation. Outcomes were assessed at time of initiation of GLP1-RA (baseline) and 3-12 months post-initiation. Nadir values between 3-12 months were utilized to assess outcomes. Results: One-hundred eighteen patients met study inclusion criteria. Seventy-percent of patients received a kidney transplant, 19.5% received a liver transplant, and 6.8% received a lung transplant. A statistically significant difference was observed in median fasting blood glucose and HbA1c at baseline to 3-12-month nadir (P < 0.0001). A significant weight loss benefit was also observed. The rate of adverse drug reactions was low. Seven-percent of patients experienced nausea, 4.2% developed pancreatitis, and 7.1% reported having had at least one hypoglycemic event. Discussion: This is the largest study evaluating GLP1-RA in organ transplantation and demonstrates GLP1-RA is both safe and effective. Further assessment on long-term use of these agents on cardiovascular and renal outcomes is still needed.

Pain Allaying Epalrestat-Loaded Lipid Nanoformulation for the Diabetic Neuropathic Pain Interventions: Design, Development, and Animal Study.

BACKGROUND: Diabetic peripheral neuropathy is the most common complication of diabetes mellitus. Epalrestat, an aldose reductase inhibitor, has been approved for clinical therapy for diabetic peripheral neuropathic pain. In the present study, solid lipid-based nanoparticles are used for oral administration of epalrestat (E-SLN) and evaluated against diabetic neuropathic pain in a rat model. METHODS: Experimental diabetes in rats was induced by a single dose of streptozotocin (STZ) administration. The therapeutic efficiency of Epalrestat nanoparticles (0.25, 0.50, 1, and 5 mg/kg) in diabetic rats was studied. STZinduced diabetic rats were treated with different doses of E-SLN for 8 weeks. The nanoparticles were orally administered at a single dose in rats, and the various parameters related to peripheral neuropathy were evaluated and compared with the bare drug. The blood glucose level was estimated by standard glucometer, HbA1c, triglycerides, total cholesterol, and liver function test (ALT and AST) were analyzed by blood samples collected from retro-orbital plexus. Oxidative stress markers and Na+K+ATPase, TNF-α, and IL-1ß levels were measured in the homogenate of sciatic nerves. Behavioral tests were also performed by the hot plate method and tail-flick method. RESULTS: E-SLN synthesized by the micro-emulsification method was 281 ± 60 nm in size, and encapsulation efficacy was found to be 88 ± 2%. Optimized E-SLN were characterized and found to be optimum in size, spherical shape, decent encapsulation efficiency, stable at acidic gastric pH, and suitable for oral delivery. E-SLNs did not significantly reverse the STZ-induced elevated blood glucose level (FBS and PPBS), HbA1c, triglycerides, and total cholesterol but significantly improved TNF-α, IL-1ß, and increased Na+K+ATPase levels, oxidative stress marker and ALT, AST in the treated rat group as compared with the diabetic group. Doses of E-SLN, i.e. 0.5, 1.0, 2.5, and 5 mg/kg, significantly increased the tail-flick latency time and hot plate response time in a dose-dependent manner compared with the diabetic group. CONCLUSION: Thus, it is suggested that E-SLN were equally effective and less hepatotoxic compared with the standard treatment of epalrestat. To the best of our knowledge, we, for the first time, propose the orally deliverable E-SLN that ameliorates STZ-induced diabetes neuropathic pain effectively as compared with conventional epalrestat.

Sodium-glucose cotransporter 1 inhibition and gout: Mendelian randomisation study.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce serum urate, but their efficacy depends on renal function which is often impaired in people with gout. SGLT1 is primarily expressed in the small intestine and its inhibition may be a more suitable therapeutic target. We aimed to investigate the association of genetically proxied SGLT1i with gout risk, serum urate levels and cardiovascular safety using Mendelian randomisation (MR). METHODS: Leveraging data from a genome-wide association study of 344,182 individuals in the UK Biobank, we identified a missense variant in the SLC5A1 gene that associated with glycated haemoglobin (HbA1c) to proxy SGLT1i. Outcome genetic data comprised 13,179 gout cases and 750,634 controls, 457,690 individuals for serum urate levels, and up to 977,323 individuals for cardiovascular safety outcomes. We applied the Wald ratio method and investigated potential genetic confounding using colocalization. RESULTS: The rs17683430 missense variant was selected to instrument SGLT1i. Genetically proxied SGLT1i was associated with 75% reduction in gout risk (OR 0.25; 95%CI 0.06, 0.99; p = 0.048) and 32.0 µmol/L reduction in serum urate (95%CI -56.7, -7.3; p = 0.01), per 6.7 mmol/mol reduction in HbA1c. SGLT1i was associated with increased levels of low-density lipoprotein cholesterol (0.37 mmol/L; 95%CI 0.17, 0.56; p = 0.0002) but not risk of coronary heart disease, stroke, or chronic kidney disease. Colocalization did not suggest that results are attributable to genetic confounding. CONCLUSION: SGLT1 inhibition may represent a novel therapeutic option for preventing gout in people with or without comorbid diabetes. Randomised trials are needed to formally investigate efficacy and safety.

The long-term effect of mTOR inhibition on lipid and glucose metabolism in tuberous sclerosis complex: data from the Dutch TSC registry.

BACKGROUND: MTOR inhibition is an effective treatment for many manifestations of tuberous sclerosis complex. Because mTOR inhibition is a disease modifying therapy, lifelong use will most likely be necessary. This study addresses the long-term effects of mTOR inhibitors on lipid and glucose metabolism and aims to provide better insight in the incidence and time course of these metabolic adverse effects in treated TSC patients. METHODS: All patients who gave informed consent for the nationwide TSC Registry and were ever treated with mTOR inhibitors (sirolimus and/or everolimus) were included. Lipid profiles, HbA1c and medication were analysed in all patients before and during mTOR inhibitor treatment. RESULTS: We included 141 patients, the median age was 36 years, median use of mTOR inhibitors 5.1 years (aimed serum levels 3.0-5.0 µg/l). Total cholesterol, LDL- and HDL-cholesterol levels at baseline were similar to healthy reference data. After start of mTOR inhibition therapy, total cholesterol, LDL-cholesterol and triglycerides increased significantly and were higher compared to healthy reference population. Mean total cholesterol levels increased by 1.0 mmol/L after 3-6 months of mTOR inhibition therapy but did not increase further during follow-up. In this study, 2.5% (3/118) of patients developed diabetes (defined as an HbA1c ≥ 48 mmol/mol) during a median follow-up of 5 years. CONCLUSIONS: Hypercholesterolemia is a frequent side effect of mTOR inhibition in TSC patients, and predominantly occurs within the first year of treatment. Although hyperglycemia is a frequent side effect in other indications for mTOR inhibition, incidence of diabetes mellitus in TSC patients was only 2.5%. This may reflect the difference of mTOR inhibition in patients with normal mTOR complex pathway function versus patients with overactive mTOR complex signaling due to a genetic defect (TSC patients).

Evaluation of Diabetes Mellitus Type 2 Control in Home-Based Primary Care Patients Managed by Clinical Pharmacy Specialists.

Purpose To evaluate the impact of pharmacist-led diabetes care in a Home-Based Primary Care (HBPC) setting. Methods This was a single-center, retrospective, cohort chart review in HBPC veterans with diabetes mellitus type 2 (DMII) at Columbia VA Health Care System. A sample size of 80 patients was calculated to meet power of 80% and a P-value of less than 0.05 was used to determine clinical significance. The primary outcome was mean hemoglobin A1C (HgbA1C) change after up to 18 months of Clinical Pharmacy Specialist (CPS) diabetes-led care stratified by baseline HgbA1C. Secondary outcomes included change in the number of diabetes medications and doses per day stratified by baseline HgbA1C. Results One hundred twelve patients were included in the final analysis based on inclusion and exclusion criteria. The mean absolute HgbA1C reduction was 0.51%, 95% CI -0.20 to -0.82 from 8.1% at baseline. For the subgroup analyses, patients with baseline HgbA1C less than 8.5%, had a nonsignificant increase in their HgbA1C, while patients with HgbA1C 8.5% or more showed significant reductions in HgbA1C (P < 0.05). Patients with baseline HgbA1C less than 6.5% had a significant decrease of 0.52, 95% CI -0.18 to -0.87 and patients with baseline HgbA1C 6.5% or more had a nonsignificant increase in the number of diabetes medications (P > 0.05). Patients with baseline HgbA1C of less than 7.5% and 9.5% or more had a decrease in the number of diabetes medication doses with results being significant for patients with HgbA1C less than 6.5%, 95% CI -0.58 to -1.89. Conclusion The results of this study suggest that HBPC CPSs are improving glycemic control in HBPC veterans while simplifying diabetic regimens with attention to hypoglycemic risk reduction.