Low Risk Of Hypoglycemia Research Articles

Problems and decisions in the management of type 2 diabetes mellitus: the role of metformin

Studies on the additional properties of metformin continue despite the long period of its use as an antihyperglycemic drug. Metformin is a member of the biguanide class of drugs and is successfully used for many years in type 2 diabetes mellitus patients with normal weight, overweight, and obesity both in monotherapy and in combination with other sugar-lowering drugs. It can be used as a drug for the management of T2DM due to its high sugar-lowering activity, low risk of hypoglycemia when used as monotherapy, neutral effect on weight with its further moderate reduction, good safety profile, and availability for most patients. A decreased peripheral insulin resistance under the influence of metformin leads to increased utilization of glucose in the liver, muscles and adipose tissue, which results in an antihyperglycemic effect and, as a consequence of this, improvement of the disease management, preventing or slowing down the development of late complications of type 2 diabetes mellitus. Metformin has a proven track record as a drug with many positive effects, which was confirmed in numerous studies in patients with various complications of diabetes mellitus and concomitant pathologies. The article presents data on the use of metformin in patients with type 2 diabetes mellitus for the purpose of preventing sarcopenic obesity and managing its symptoms. Metformin presents some features of interest in preventing the development and treatment of non-alcoholic fatty liver disease and polycystic ovary syndrome.

Exendin-4 affects calcium signalling predominantly during activation and activity of beta cell networks in acute mouse pancreas tissue slices.

Tight control of beta cell stimulus-secretion coupling is crucial for maintaining homeostasis of energy-rich nutrients. While glucose serves as a primary regulator of this process, incretins augment beta cell function, partly by enhancing cytosolic [Ca2+] dynamics. However, the details of how precisely they affect beta cell recruitment during activation, their active time, and functional connectivity during plateau activity, and how they influence beta cell deactivation remain to be described. Performing functional multicellular Ca2+ imaging in acute mouse pancreas tissue slices enabled us to systematically assess the effects of the GLP-1 receptor agonist exendin-4 (Ex-4) simultaneously in many coupled beta cells with high resolution. In otherwise substimulatory glucose, Ex-4 was able to recruit approximately a quarter of beta cells into an active state. Costimulation with Ex-4 and stimulatory glucose shortened the activation delays and accelerated beta cell activation dynamics. More specifically, active time increased faster, and the time required to reach half-maximal activation was effectively halved in the presence of Ex-4. Moreover, the active time and regularity of [Ca2+]IC oscillations increased, especially during the first part of beta cell response. In contrast, subsequent addition of Ex-4 to already active cells did not significantly enhance beta cell activity. Network analyses further confirmed increased connectivity during activation and activity in the presence of Ex-4, with hub cell roles remaining rather stable in both control experiments and experiments with Ex-4. Interestingly, Ex-4 demonstrated a biphasic effect on deactivation, slightly prolonging beta cell activity at physiological concentrations and shortening deactivation delays at supraphysiological concentrations. In sum, costimulation by Ex-4 and glucose increases [Ca2+]IC during beta cell activation and activity, indicating that the effect of incretins may, to an important extent, be explained by enhanced [Ca2+]IC signals. During deactivation, previous incretin stimulation does not critically prolong cellular activity, which corroborates their low risk of hypoglycemia.

Automated Insulin Delivery for Pregnant Women With Type 1 Diabetes: Where Do We Stand?

Automated insulin delivery (AID) systems mimic an artificial pancreas via a predictive algorithm integrated with continuous glucose monitoring (CGM) and an insulin pump, thereby providing AID. Outside of pregnancy, AID has led to a paradigm shift in the management of people with type 1 diabetes (T1D), leading to improvements in glycemic control with lower risk for hypoglycemia and improved quality of life. As the use of AID in clinical practice is increasing, the number of women of reproductive age becoming pregnant while using AID is also expected to increase. The requirement for lower glucose targets than outside of pregnancy and for frequent adjustments of insulin doses during pregnancy may impact the effectiveness and safety of AID when using algorithms for non-pregnant populations with T1D. Currently, the CamAPS® FX is the only AID approved for use in pregnancy. A recent randomized controlled trial (RCT) with CamAPS® FX demonstrated a 10% increase in time in range in a pregnant population with T1D and a baseline glycated hemoglobin (HbA1c) ≥ 48 mmol/mol (6.5%). Off-label use of AID not approved for pregnancy are currently also being evaluated in ongoing RCTs. More evidence is needed on the impact of AID on maternal and neonatal outcomes. We review the current evidence on the use of AID in pregnancy and provide an overview of the completed and ongoing RCTs evaluating AID in pregnancy. In addition, we discuss the advantages and challenges of the use of current AID in pregnancy and future directions for research.

Bexagliflozin as an Adjunct Therapy to Diet and Exercise to Improve Glycaemic Control in Adults with Type 2 Diabetes.

Type 2 diabetes (T2D) is one of the leading causes of morbidity and mortality worldwide. Currently, over 10.5% of the adult population has been diagnosed with T2D, and almost 12% of total health expenditure is spent exclusively on T2D management globally. Sodium-glucose cotransporter-2 inhibitors are a relatively new class of oral antidiabetic agents that act by inhibiting renal sodium and glucose reabsorption. Except for their glucose-l owering effects, they have been associated with a more significant weight loss and blood pressure reduction and a lower risk of hypoglycaemia than other commonly prescribed antidiabetic drugs. On 20 January 2023, bexagliflozin became the fifth orally administered sodium-glucose transporter 2 inhibitor to be approved by the US Food and Drug Administration for the treatment of T2D as an adjunct therapy to diet and exercise in the USA after dapagliflozin, canagliflozin, empagliflozin and ertugliflozin. This review aims to discuss the current evidence on the efficacy and safety of bexagliflozin, which provides an important alternative treatment option for patients with T2D.

Expert eValuation of Efficacy and Rationality of Vildagliptin "EVER-Vilda": An Indian Perspective.

Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor is effective in reducing HbA1c levels in patients with type 2 diabetes (T2DM) when administered as monotherapy, dual or triple combination therapy. In India, Vildagliptin is commonly prescribed in T2DM patients because it reduces mean amplitude of glycemic excursion (MAGE), has lower risk of hypoglycemia and is weight neutral. Early combination therapy with vildagliptin and metformin is effective and well-tolerated in patients with T2DM, regardless of age or ethnicity. In view of already existing data on vildagliptin and the latest emerging clinical evidence, a group of endocrinologists, diabetologists and cardiologists convened for an expert group meeting to discuss the role and various combinations of vildagliptin in T2DM management. This practical document aims to guide Physicians and Specialists regarding the different available strengths and formulations of vildagliptin for the initiation and intensification of T2DM therapy.

Comparison of GLP-1 Receptor Agonists, SGLT-2 Inhibitors, and DPP-4 Inhibitors as an Add-On Drug to Insulin Combined With Oral Hypoglycemic Drugs: Umbrella Review.

Background: The objective was to evaluate the efficacy of the combination of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter 2 inhibitor (SGLT-2i) in the treatment of Type 2 diabetes with poor efficacy of basic insulin and metformin/sulfonylurea by umbrella review. Materials and Methods: Forming the data of publication of each database through 13 September 2022, PubMed, EMBASE, and Cochrane Library were surveyed. Results: A total of seven meta-analyses were included in the umbrella review. The combination of GLP-1 RA (WMD -3.41 [-5.61, -1.21], p = 0.002), SGLT-2i (WMD -5.34 [-9.56, -1.13], p = 0.013), and DPP-4i (WMD -5.56 [-7.39, -3.73], p ≤ 0.001) can significantly reduce HbA1c levels, respectively. The combination of GLP-1 RA (WMD -1.55 [-2.92, -0.18], p = 0.027), SGLT-2i (WMD -2.96 [-6.68, 0.77], p = 0.12), and DPP-4i (WMD -2.05 [-2.82, -1.28], p ≤ 0.001) can significantly reduce fasting plasma glucose (FPG) levels, respectively. The combination of GLP-1 RA (WMD -3.24 [-5.14, -1.34], p < 0.001) can significantly reduce body weight of Type 2 diabetes mellitus (T2DM). The dose of basic insulin in diabetes patients after combined use of GLP-1 RA (WMD -2.74 [-4.26, -1.22], p ≤ 0.001) was significantly reduced. The combination use of GLP-1 RAs (OR 1.28 [1.05, 1.56], p = 0.017) increases the risk of hypoglycemia. Conclusions: The combination of GLP-1 RAs, DPP-4i, and SGLT-2i can effectively lower HbA1c and FPG in T2DM patients who have poor therapeutic effects on basic insulin combined with metformin/sulfonylureas, respectively. Compared to placebo, GLP-1 RAs can significantly reduce body weight and basic insulin dosage, while DPP-4i and SGLT-2i have a lower risk of hypoglycemia. Trial Registration: CRD42023410345.

Tratamento de diabetes mellitus tipo 2 em um sagui-de-orelha-preta (Callithrix penicillata)

ABSTRACT: Type-2 diabetes mellitus (T2DM) is characterized by defects in insulin secretion and combined peripheral resistance to the hormone. Several non-human primates (NHP) species develop T2DM, mainly captive animals with reduced physical activity and incorrect feeding. This case report describes the T2DM treatment of a black-eared marmoset (Callithrix penicillata) by diet reformulation and metformin oral administration. An adult female was diagnosed with T2DM after hyperglycemia and high serum fructosamine associated with glycosuria and obesity. Metformin hydrochloride (125mg/animal, orally, q24h) associated with feeding intervention was started. After 26 days, a significant reduction in weight, glycemia, and serum fructosamine could be observed, showing satisfactory results for the adopted therapy. Metformin is considered a safe drug for T2DM treatment due to its low hypoglycemia risk. The new diet consisted of sweet potato, squash, and varied fruits offered twice daily. In addition, thawed-mice newborns, egg whites, and small portions of pelleted primate food. In the present report, metformin use, associated with a low glycemic index diet, was effective in treating this particular marmoset and may present a potential for T2DM treatment in other NHPs.

Umbilical artery cord blood glucose predicted hypoglycemia in gestational diabetes mellitus and other at-risk newborns

BackgroundTo explore the value of umbilical artery cord blood glucose (UACBG) in predicting hypoglycemia in gestational diabetes mellitus (GDM) and other at-risk newborns, and to provide a cut-off UACBG value for predicting hypoglycemia occurrence.MethodsIn this prospective study, we enrolled at-risk infants delivered vaginally, including neonates born to mothers with GDM, premature, macrosomic, and low birth weight. We separated the infants into GDM group and other at-risk group. All subjects underwent UACBG measurement during delivery. Neonatal peripheral blood glucose measurement was performed at 0.5 and 2 h after birth. The predictive performance of UACBG for neonatal hypoglycemia was assessed using receiver operating characteristic curve (ROC), area under curve (AUC), sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV).Results916 newborns were included, with 538 in GDM group and 378 in other at-risk group. 85 neonates were diagnosed hypoglycemia within 2 h after birth, including 36 belonging to GDM group and 49 to other at-risk group. For hypoglycemia prediction within 2 h, the best cut-off of UACBG was 4.150 mmol/L, yielding an AUC of 0.688 (95% CI 0.625–0.751) and a NPV of 0.933. In detail, the AUC was 0.680 in GDM group (95% CI 0.589–0.771), with the optimal cut-off of 4.150 mmol/L and a NPV of 0.950. In other at-risk group, the AUC was 0.678(95% CI 0.586–0.771), the best threshold was 3.950 mmol/L and the NPV was 0.908. No significant differences were observed between GDM group and other at-risk group in AUC at 0.5 h, 2 h and within 2 h.ConclusionsUACBG has a high NPV for predicting neonatal hypoglycemia within 2 h after birth. It was implied that individuals with cord blood glucose levels above the threshold were at lower risk for hypoglycemia. UACBG monitoring provides evidence for subsequent classified management of hypoglycemia.

Antidiabetic phytodrug from Maerua angolensis DC: Formulation, standardization, in vitro and in vivo evaluations

Maerua angolensis is a shrub or small tree widely distributed in tropical Africa. The plant materials are used for various ethnomedicinal applications across the region, including the prevention and treatment of diabetes. This study was aimed to evaluate the antidiabetic potential of formulated freeze-dried aqueous extract of Maerua angolensis leaves using standard in vitro and in vivo experimental models. Infusion extract of the plant's powdered dried leaves was prepared, the resultant extract was freeze-dried and formulated (denoted FIEMa). The physicochemical, quantitative and qualitative phytochemical constituents of FIEMa were determined using analytical techniques (UV-visible and HPLC). The antidiabetic activity of the reconstituted formulation was investigated using in vitro and in vivo models. The in vitro activity was assessed using Phosphomolybdenum assay and DPPH (2,2-Diphenyl-1-picrylhydrazyl) radical scavenging activity for antioxidant effect, and α-amylase inhibition and α- glycosidase inhibition assays. The assays of the normoglycemic, oral glucose load tolerance, and single-dose alloxan (150 mg/kg) induced diabetes in rats were used for in vivo antidiabetic activity. The results show that FIEMa contains valuable phytochemicals. It exhibited antioxidant effect, α-amylase and α- glucosidase inhibition activities. FIEMa did not significantly reduce blood glucose levels (BGL) in normoglycemic mice but produced a significant reduction of BGL in the oral glucose tolerance test. In alloxan-induced diabetic rats, significant reductions of BGL were observed in groups treated with high doses of FIEMa in the single-dose study and from the second week onwards in the repeated dose study. It also exhibited less reduction in body weight compared to the control group. The findings indicate that FIEMa has an antidiabetic activity, low risk of hypoglycemia, and body weight loss. The valuable phytochemicals plausibly mediate this effect, especially the dominant betulinic acid detected in FIEMa, most likely acting in synergy.

Reversible acute blindness in suspected metformin-associated lactic acidosis: a case report

BackgroundMetformin is commonly used for the treatment of type 2 diabetes mellitus. Its multiple advantages include low risk of hypoglycemia, weight neutrality, low cost, and cardioprotective and anti-inflammatory effects. Renal insufficiency is one of the contraindications for its use. Inadvertent prescription in patients with renal insufficiency may lead to metformin-associated lactic acidosis, which brings a high risk of mortality. The early recognition and management of metformin-associated lactic acidosis are essential.Case reportWe present the case of a 58-year-old Hui woman with a history of type 2 diabetes mellitus with nephropathy and heart disease for which she was treated with metformin, insulin, and heart medications. She developed nausea, vomiting, anion gap metabolic acidosis due to hyperlactatemia, and acute kidney injury. She was hospitalized to receive intravenous hydration and correction of metabolic acidosis after she suddenly developed blindness. The diagnostic workup ruled out central causes and her symptoms resolved briefly after continuous venovenous hemodialysis was initiated, confirming the diagnosis of metformin-associated lactic acidosis.ConclusionsMetabolic disruption can cause acute blindness. Metabolic acidosis in a patient with a history of metformin intake should suggest the possibility of metformin-associated lactic acidosis, which must be treated immediately, without waiting for the results of other examinations, especially in patients with sudden blindness. Further study of reversible blindness-associated severe metabolic acidosis is needed.

Diabetes Mellitus in Acute Coronary Syndrome.

The global prevalence of diabetes mellitus (DM) has led to a pandemic, with significant microvascular and macrovascular complications including coronary artery disease (CAD), which worsen clinical outcomes and cardiovascular prognosis. Patients with both acute coronary syndrome (ACS) and DM have worse prognosis and several pathophysiologic mechanisms have been implicated including, insulin resistance, hyperglycemia, endothelial dysfunction, platelet activation and aggregations as well as plaque characteristics and extent of coronary lesions. Therefore, regarding reperfusion strategies in the more complex anatomies coronary artery bypass surgery may be the preferred therapeutic strategy over percutaneous coronary intervention while both hyperglycemia and hypoglycemia should be avoided with closed monitoring of glycemic status during the acute phase of myocardial infraction. However, the best treatment strategy remains undefined. Non-insulin therapies, due to the low risk of hypoglycemia concurrently with the multifactorial CV protective effects, may be proved to be the best treatment option in the future. Nevertheless, evidence for the beneficial effects of glucagon like peptide-1 receptor agonists, dipeptidyl-peptidase 4 inhibitors and sodium glycose cotransporter 2 inhibitors, despite accumulating, is not robust and future randomized control trials may provide more definitive data.

Advanced Hybrid Closed-Loop System Achieves and Maintains Recommended Time in Range Levels for Up To 2 Years: Predictors of Best Efficacy.

Aim: To evaluate the long-term efficacy, up to 2 years, of an advanced hybrid closed-loop (AHCL) system and to assess predictors of best results of the therapy. Methods: We retrospectively evaluated 296 adults with type 1 diabetes mellitus [mean age 42.8 ± 16.5 years, men 42.9%, duration of diabetes 22.5 ± 12.8 years, body mass index 24.9 ± 4.7 kg/m2, baseline glycated hemoglobin (HbA1c) 63.4 ± 12.2 mmol/mol (8.0 ± 1.1%) ] who used the MiniMed™ 780G system. Demographic and clinical data were recorded. Continuous glucose monitoring (CGM)-derived metrics and insulin requirement were analyzed from the 4 weeks before and from every quarter after the switch to the AHCL system. Results: In the first quarter of AHCL treatment, all CGM metrics improved. Time in range (TIR) increased from 58.1 ± 17.5% to 70.3 ± 9.5% (P < 0.0001). The improvement lasted for up to 2 years of observation regardless of previous insulin therapies. Throughout the period of observation, 53.4% of participants achieved mean TIR >70%, 92.6% mean time below range <4%, and 46% mean glucose management indicator <53 mmol/mol (7.0%). At univariable logistic regression older age, lower baseline HbA1c and insulin requirement were associated with mean TIR >70%. At multivariable analysis, lower HbA1c remained independently associated with a better glycemic control. However, mean TIR increased more in participants with a higher baseline HbA1c. Conclusions: Switching to an AHCL leads to a rapid improvement in glycemic control lasting for up to 24 months along with a low risk for hypoglycemia, confirming the safety of the system. Lower baseline HbA1c was the main predictor of better efficacy of therapy, although higher baseline HbA1c was associated with the greatest improvement in mean TIR.

FRI657 Case Series On GLP-1 Receptor Agonist Related Acute Pancreatitis

Abstract Disclosure: A.U. Kulkarni: None. V. Mehta: None. M. Renzu: None. K. Pereira: None. M.A. Rather: None. Introduction: Acute pancreatitis (AP) has now become one of the leading causes of GI related hospital admissions in the United States. With increasing use of GLP-1 Receptor Agonists (GLP-1 RA) in T2DM and obesity, they are now being identified as one such class of drugs which can cause AP. We present this case series to discuss these adverse effects. Case 1: A 50 yo AA male with a history of T2DM and hypertension presented with acute severe epigastric pain, nausea and vomiting for 5 days. Vitals were stable. On physical exam, tenderness in the RUQ was noted. Labs revealed lipase of 313 U/l (11-82 U/l), BG of 213 mg/dL, HbA1c 11.3, normal LFT and lipid panel. Blood EtOH was negative. He denied tobacco, alcohol, and illicit drug use. CT abdomen showed acute interstitial edematous pancreatitis without cholelithiasis or choledocholithiasis. Liver ultrasound showed hepatic steatosis. He noted recent initiation of Semaglutide 6 months ago which was stopped 3 weeks prior to this visit due to abdominal discomfort. Previous Dulaglutide therapy was also discontinued due to GI intolerance. Home medication for DM otherwise included metformin and basal insulin. Case 2: A 68 yo AA woman with a history of T2DM, hypothyroidism presented after a week of severe epigastric pain, radiating to her back, with nausea and vomiting. Labs showed lipase 593 U/l (11-82 U/l), BG of 427 mg/dl, HbA1c of 10. Social history was non-contributory. CT Abdomen showed AP and no gallstones or bile duct dilatation. LFTs and lipid panel were unremarkable. Chart review noted prior admission for AP a month ago. Her home medications were basal Insulin and Dulaglutide (4 yrs). Drug induced AP from Dulaglutide was suspected. Lack of clinical improvement after 3 days of management prompted RUQ ultrasound, which was prematurely terminated due to pain during the scan. Subsequent CCK-HIDA was negative for acute cholecystitis but noted low gallbladder EF. Thus dulaglutide was identified as a potential trigger along with gallbladder dysmotility as a possible etiology for her recurrent AP. Both patients were managed with IV fluids, NPO diet and morphine. They were instructed to stop GLP-1 RA and discharged with PCP follow-up. Discussion: GLP-1 RA are now being widely used due to low risk of hypoglycemia and weight loss. Clinical trials with GLP-1 RA have shown mild, asymptomatic increase in lipase, amylase levels as well as rare incidences of AP. This has been attributed to the stimulation of pancreatic beta cells and exocrine duct cells leading to acinar cell hypertrophy, proinflammatory cytokine induction, causing pancreatic injury. Though drug-induced AP is uncommon and is a diagnosis of exclusion, detailed history taking, medication review and investigating for all other causes is of utmost importance. A good understanding of the drugs associated with AP should alert the physician to identify these agents and promptly discontinue them to prevent further complications. Presentation: Friday, June 16, 2023

LIVE INDIA: Effectiveness of Gla-100 in a Post hoc Pooled Analysis of FINE ASIA and GOAL Registries.

Real-world evidence on insulin glargine 100U/ml (Gla-100) initiation in Indian type 2 diabetes mellitus (T2DM) individuals is limited. The present study aimed to evaluate the effectiveness of Gla-100 in insulin-naïve T2DM participants from India. This post hoc analysis includes real-world data of insulin-naïve Indian participants with T2DM who started Gla-100 treatment in two Asian registries: FINE ASIA and GOAL. Changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), body weight, insulin dose, and incidence of hypoglycemia from baseline to 6months were assessed. A total of 955 participants with T2DM were identified and analyzed. The mean [standard deviation (SD)] age and duration of diabetes were 54.7 (9.8) years and 9.8 (6.3) years, respectively. Mean HbA1c and FPG were significantly reduced after 6months of Gla-100 treatment [-2.07 (1.4) %; -94.4 (65.2) mg/dl, respectively]. HbA1c targets of < 7.0% and < 7.5% were achieved by 292 (30.6%) and 589 (61.7%) study participants, respectively. The overall incidence of hypoglycemia was low (n = 52; 5.4%); only two participants (0.2%) reported severe hypoglycemia. Insulin was titrated with a mean (SD) increment of 2.5 (5.6) U/day after 6months, leading to a mean Gla-100 dose of 18.2 (8.9) U/day. Mean body weight remained unchanged from baseline to 6months (- 0.1kg). In routine clinical practice, Gla-100 significantly improved glycemic parameters after 6months of treatment with a low risk of hypoglycemia and no weight change in participants with T2DM.

Glycemic and Economic Outcomes in Elderly Patients with Type2 Diabetes Initiating Dulaglutide Versus Basal Insulin in a Real-World Setting in the United States: The DISPEL-Advance Study.

Treatments like glucagon-like peptide-1 receptor agonists carry low hypoglycemia risk and are recommended for elderly patients with type2 diabetes (T2D), while some routine treatments, like insulin, increase hypoglycemia risk. The DISPEL-Advance (Dulaglutide vs Basal InSulin in Injection Naïve Patients with Type2 Diabetes: Effectiveness in ReaL World) study compared glycemic outcomes, healthcare resource utilization, and costs in elderly patients with T2D who initiated treatment with dulaglutide versus those initiating treatment with basal insulin. This observational, retrospective cohort study used data from the Optum Research Database. Medicare Advantage patients (≥ 65years) with T2D were assigned to dulaglutide or basal insulin cohorts based on pharmacy claims and propensity score matched on demographic and baseline characteristics. Change in HbA1c, 12-months follow-up HbA1c, and follow-up all-cause and diabetes-related healthcare resource utilization and costs were compared. Propensity score matching yielded well-balanced cohorts with 1891 patients each (mean age: dulaglutide, 72.09years; basal insulin, 72.56years). The dulaglutide cohort had significantly greater mean HbA1c reduction from baseline to follow-up than basal insulin cohort (- 0.95% vs - 0.69%; p < 0.001). The dulaglutide cohort had significantly lower mean all-cause and diabetes-related medical costs (all-cause: $8306 vs $12,176; diabetes-related: $4681 vs $7582 respectively; p < 0.001) and lower mean all-cause total costs ($18,646 vs $20,972, respectively; p = 0.007) than basal insulin cohort. The dulaglutide cohort had significantly lower all-cause and diabetes-related total costs per 1% change in HbA1c than basal insulin cohort (all-cause: $19,729 vs $30,334; diabetes-related: $12,842 vs $17,288, respectively; p < 0.001). Elderly patients with T2D initiating dulaglutide had greater HbA1c reduction, lower mean all-cause medical and total costs, lower diabetes-related medical costs, and lower total all-cause and diabetes-related costs per 1% change in HbA1c than patients initiating basal insulin. Future studies assessing medications that do not increase hypoglycemia risk could help inform therapeutic strategies in elderly patients.

Exercise-induced hematuria exacerbated by improper hydration, low RBC MCV and dapagliflozin use

BackgroundDapagliflozin is a reversible, highly potent, and selective Sodium-Glucose Co-Transporter-2 inhibitor indicated for the treatment of type 2 diabetes. It is generally well tolerated, with a low risk of hypoglycaemia and diabetic ketoacidosis. Case presentationWe report a new adverse effect of dapagliflozin in a form of a transient hematuria, presenting in a 54-years-old male patient with type 2 diabetes after exercise and insufficient hydration. The process of hematuria in the patient is strongly linked with initial period of treatment. ConclusionDapagliflozin appears to have a rare adverse effect in the form of transient hematuria. Exercise, insufficient hydration, and low RBC MCV may play a role in such episodes.

Results of a 12-month follow-up of patients with type 2 diabetes mellitus after hospitalization with COVID-19: gliclazide MR use in the hospital and metabolic status at the posthospital stage

BACKGROUND: The role of antidiabetic drugs in inpatient with COVID-19 and type 2 diabetes mellitus (T2DM) is usually considered in the context of target glycemiа maintaining. Except for insulin therapy sulfonylurea may be used in moderate COVID-19. The use of original gliclazide MR has advantages due to low risk of hypoglycemia and established cardio- and nephroprotective effects. But it is not clear whether the choice of antidiabetic drugs during hospitalization may affect patient’s condition in post-COVID period.AIM:. To assess the 12-month dynamics of carbohydrate metabolism in patients with T2DM after hospitalization for COVID-19 considering the character of hypoglycemic therapy in the hospital and the use of gliclazide MRMATERIALS AND METHODS: A 12-month prospective study was performed; T2DM patients were observed after hospitalization for COVID-19. They received in hospital: 1) original gliclazide MR (Diabeton MR, n=20) and 2) insulin (control group, n=20). Changes in antidiabetic therapy, glycemic control and biochemical tests were assessed at baseline and after 3, 6, 12 months. RESULTS: In the main and control groups the intensification of T2DM therapy was observed: the proportion of patients without hypoglycemic drugs decreased within a year by 3.0 (p = 0.001) and 2.8 (p =0.010) times respectively. Mean HbA1c values,the dynamics of inflammation markers and transaminases in both groups were similar (p&gt;0.05 at all visits). Blood creatinine was at baseline 82.9±18.67 and 120.9±45.52 µmol/l (p=0.010), after 3 months — 88.0±18.77 and 104, 5±17.99 µmol/l (p=0.024), after 6 months — 89.3±12.17 and 97.5±9.03 µmol/l (p=0.072), after 12 months — 86.7±10.50 and 93.9±16.76 µmol/l (p=0.16). According to the data obtained during «3 months» visit, the dose of original gliclazide MR was directly correlated with the improvement in renal function in terms of glomerular filtration rateGFR (R=0,59, р=0,010). In addition, there was a close-to-significance correlation between continued gliclazide MR at visit 3 and improvement in GFR at visit 6 (R=0.31, p=0.076).CONCLUSION: The post-hospital period in patients with COVID-19 and T2DM was characterized by a tendency to hyperglycemia and increased need for hypoglycemic therapy. The use of original gliclazide MR by in patients with moderate COVID-19 and T2DM is appropriate and safe in terms of clinical and metabolic parameters dynamics during long-term post-hospital follow-up. When original gliclazide MR is continued during the post-hospital period its nephroprotective properties may contribute to the process of renal functions normalization which should be confirmed by further research.

Risk factors for hypoglycemia in patients with type 2 diabetes mellitus after intensive insulin therapy and blood glucose monitoring strategy.

To explore the risk factors for hypoglycemia in patients with type 2 diabetes mellitus (T2DM) after intensive insulin therapy and the blood glucose monitoring strategy. A total of 172 T2DM patients diagnosed from March 2019 to March 2021 were randomly divided into training (n=115) and test sets (n=57), and given intensive insulin therapy. After treatment, the training set was divided into hypoglycemia (n=35) and non-hypoglycemia groups (n=80). Univariate and multivariate logistic regression analyses were performed. Then 120 patients were divided into instantaneous scanning glucose test system monitoring (observation) and glucometer monitoring (control) groups. The diagnostic values of the two methods were validated using receiver operator characteristic curves. Course of disease, body mass index, fasting C-peptide and creatinine were independent risk factors for hypoglycemia, while instantaneous scanning glucose test system monitoring and glucometer monitoring were protective factors (P<0.05). The model had high predictive value. The observation group had shorter time of blood glucose reaching the standard, smaller insulin dose, and lower risk of hypoglycemia than those of the control group (P<0.05). During intensive insulin therapy by multiple subcutaneous injections, the clinical effect of instantaneous scanning glucose test system on T2DM patients is better than that of glucometer.

The effect of GLP-1 receptor agonist lixisenatide on experimental diabetic retinopathy.

Glucagon-like peptide-1 receptor agonists are effective treatments for type 2 diabetes, effectively lowering glucose without weight gain and with low risk for hypoglycemia. However, their influence on the retinal neurovascular unit remains unclear. In this study, we analyzed the effects of the GLP-1 RA lixisenatide on diabetic retinopathy. Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats, acellular capillaries and pericytes (quantitative retinal morphometry), neuroretinal function (mfERG), macroglia (GFAP western blot) and microglia (immunohistochemistry) quantification, methylglyoxal (LC-MS/MS) and retinal gene expressions (RNA-sequencing) were determined. The antioxidant properties of lixisenatide were tested in C. elegans. Lixisenatide had no effect on glucose metabolism. Lixisenatide preserved the retinal vasculature and neuroretinal function. The macro- and microglial activation was mitigated. Lixisenatide normalized some gene expression changes in diabetic animals to control levels. Ets2 was identified as a regulator of inflammatory genes. In C. elegans, lixisenatide showed the antioxidative property. Our data suggest that lixisenatide has a protective effect on the diabetic retina, most likely due to a combination of neuroprotective, anti-inflammatory and antioxidative effects of lixisenatide on the neurovascular unit.

A safe approach to the treatment of type 2 diabetes in elderly patients

Introduction. Type 2 diabetes is a significant medical problem. The solution to this problem lies not only in lowering the patient’s blood glucose level, but also in preventing the complications of diabetes, influencing insulin resistance and normalizing body weight.Aim. To develop an effective and safe treatment regimen for elderly women with type 2 diabetes, which is aimed at compensating carbohydrate metabolism, improving lipid metabolism and anthropometric parameters.Materials and methods. The study involved 80 women with type 2 diabetes aged 60 to 74 years, who were divided into 2 groups of 40 people. Group 1 included patients with type 2 diabetes receiving traditional therapy for type 2 diabetes. Patients of the group 2 received the method of treatment developed by us, including, in addition to the traditional regimen, the drug Subetta®, cholecalciferol drops. All women collected complaints and anamnesis, assessed anthropometric parameters, glucose, glycated hemoglobin, vitamin D, lipid profile.Results. All patients with type 2 diabetes initially were not compensated for carbohydrate metabolism, had abdominal obesity, atherogenic dyslipidemia, and vitamin D deficiency. Anthropometric parameters significantly improved, glucose and HbA1c levels decreased to target values in patients of group 2 after 6 months against the background of the use of Subetta® and cholecalciferol. Also in this group, the indicators of lipid metabolism improved: the levels of cholesterol, LDL, triglycerides decreased, and the levels of HDL increased. Vitamin D levels reached target range. No episodes of hypoglycemia were recorded.Conclusions. The addition of Subetta® and cholecalciferol to the treatment of patients with type 2 diabetes contributed to the achievement of target indicators of carbohydrate metabolism, improved lipid profile, and weight loss. This method of treatment is well tolerated and has a low risk of hypoglycemia, which is especially important for elderly patients.