scholarly journals Combination Therapy with Empagliflozin and Insulin Results in Successful Glycemic Control: A Case Report of Uncontrolled Diabetes Caused by Autoimmune Pancreatitis and Subsequent Steroid Treatment

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Miyako Kishimoto ◽  
Kazuhide Yamaoki ◽  
Masayuki Adachi
Keyword(s):  
Magnetic Resonance ◽  
Glycemic Control ◽  
Autoimmune Pancreatitis ◽  
Glucose Transporter ◽  
Sglt2 Inhibitor ◽  
Insulin Dosage ◽  
Diabetic Patients ◽  
Total Dosage ◽  
Prednisolone Therapy ◽  
Glucose Transporter 2

A 66-year-old Japanese male presented with thirst, polyuria, and hemoglobin A1c and postprandial glucose levels (13.1% and 529 mg/dL, respectively) that indicated severe hyperglycemia. Based on his high immunoglobulin G4 level and the results of magnetic resonance imaging and magnetic resonance cholangiopancreatography, we diagnosed him with autoimmune pancreatitis. Insulin was initiated to control his diabetes. One month later, the patient commenced on prednisolone therapy for the treatment of autoimmune pancreatitis, after which his total insulin dosage increased to a maximum of 52 units/day. When the prednisolone dosage was later tapered, the patient’s total dosage of insulin was reduced to 42 units/day. However, he had gained 3.6 kg from the start of prednisolone therapy, and 42 units/day was insufficient for maintaining glycemic control. Thus, empagliflozin, a sodium-dependent glucose transporter 2 (SGLT2) inhibitor, was added. Thereafter, we were able to reduce the patient’s total dosage of insulin; it was eventually discontinued with good glycemic control and weight loss. Such results suggest that the combination of insulin with an SGLT2 inhibitor may be a viable option for the treatment of diabetic patients on prednisolone therapy.

scholarly journals HYPERCALCEMIC PATIENT DIAGNOSED WITH PRIMARY HYPERPARATHYROIDISM AFTER DAPAGLIFLOZIN TREATMENT

2020 ◽  
Vol 6 (6) ◽  
pp. e319-e321
Author(s):  
Pınar Akhanlı ◽  
Sema Hepsen ◽  
Bekir Ucan ◽  
Güleser Saylam ◽  
Erman Cakal
Keyword(s):  
Magnetic Resonance Imaging ◽  
Computed Tomography ◽  
Magnetic Resonance ◽  
Primary Hyperparathyroidism ◽  
Glucose Transporter ◽  
Calcium Excretion ◽  
Resonance Imaging ◽  
Glucose Transporter 2 ◽  
Laboratory Test Results ◽  
The Right

Objective: Hypercalcemia associated with the use of sodium-glucose transporter-2 (SGLT-2) inhibitors is very rare. Only 2 cases have been reported in the current literature. In these cases hypercalcemia occurred with the use of SGLT-2 inhibitors taken with thiazides and excessive calcium salts. We present a case of hypercalcemia and primary hyperparathyroidism diagnosed after dapagliflozin treatment. Methods: We describe the medical history, laboratory test results, parathyroid ultrasound, 4-dimensional computed tomography-magnetic resonance imaging, and histopathology findings of the patient. Results: A 49-year-old man with 5-year history of type 2 diabetes mellitus was found to have hypercalcemia with corrected calcium of 11.28 mg/dL (reference range [RR] is 8.8 to 10.6 mg/dL) 6 months after starting dapagliflozin. Previous records showed normocalcemia for many years. Parathyroid hormone level was 70.8 pg/mL (RR is 15 to 65 pg/mL) and 24-hour urinary calcium excretion level was 492 mg/day (RR is 100 to 300 mg/day). On parathyroid ultrasound, a 4 × 9 × 14-mm hypoechoic lesion inferior to the right thyroid lobe was detected. A 15 × 10 × 9-mm oval lesion was observed in the right paratracheal area. A lesion at T1 vertebra level was also seen on 4-dimensional computed tomography-magnetic resonance imaging. The patient underwent lower right parathyroidectomy. Histopathology confirmed the diagnosis of parathyroid adenoma. The patient was asymptomatic 3 months after the operation with a normal corrected calcium level of 9.2 mg/dL. Conclusions: SGLT-2 inhibitors could have unmasked an underlying mild hyperparathyroidism, as they can increase predisposition to hypercalcemia when used with medications causing it. Volume depletion caused by SGLT-2 inhibitors may also contribute to hypercalcemia. For these reasons, calcium levels should be monitored in patients taking SGLT-2 inhibitors.

scholarly journals Nephroprotection by SGLT2i in CKD Patients: May It Be Modulated by Low-Protein Plant-Based Diets?

2020 ◽  
Vol 7 ◽  
Author(s):  
Adamasco Cupisti ◽  
Domenico Giannese ◽  
Diego Moriconi ◽  
Claudia D'Alessandro ◽  
Massimo Torreggiani ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Glucose Transporter ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Type 2 Diabetic Patients ◽  
Low Protein ◽  
Glucose Transporter 2 ◽  
Ckd Stage ◽  
Single Nephron ◽  
End Stage

Sodium-glucose-transporter 2 inhibitors (SGLT2i) are a new class of anti-diabetic drugs that in large trials such as CREDENCE have shown also a reduction of glomerular hyperfiltration and albuminuria in type 2 diabetic patients. Hence, the interest toward SGLT2i is focused toward this potential nephroprotective effect, in order to reduce the progression to overt nephropathy, and it seems to be confirmed in the most recent DAPA-CKD trial. This is the reason why the indication for SGLT2i treatment has been extended to chronic kidney disease (CKD) patients with eGFR up to 30 ml/min, namely with CKD stage 1–3. In patients with CKD stage 3 to 5, the most recent KDIGO guidelines recommend low-protein diet and plant-based regimens to delay end-stage kidney disease (ESKD) and improve quality of life. Similarly to SGLT2i, low-protein diets exert renal-protective effects by reducing single nephron hyperfiltration and urinary protein excretion. Beyond the glomerular hemodynamic effects, both protein restriction and SGLT2i are able to restore autophagy and, through these mechanisms, they may exert protective effects on diabetic kidney disease. In this perspective, it is likely that diet may modulate the effect of SGLT2i in CKD patients. Unfortunately, no data are available on the outcomes of the association of SGLT2i and low-protein and/or vegan diets. It is therefore reasonable to investigate whether CKD patients receiving SGLT2i may have further advantages in terms of nephroprotection from the implementation of a low-protein and/or plant-based diet or whether this association does not result in an additive effect, especially in vascular nephropathies.

New Quinazoline-Sulfonylurea Conjugates: Design, Synthesis and Hypoglycemic Activity

2019 ◽  
Vol 15 (6) ◽  
pp. 634-647
Author(s):  
Sahar M. Abou-Seri ◽  
AlShaimaa M. Taha ◽  
Mona A. Mohamed ◽  
Nour M. Abdelkader
Keyword(s):  
Glucose Transporter ◽  
Insulin Level ◽  
Diabetic Animal ◽  
Pancreatic Tissue ◽  
Diabetic Rats ◽  
Hypoglycemic Effect ◽  
Diabetic Patients ◽  
Design Synthesis ◽  
Bioisosteric Replacement ◽  
Glucose Transporter 2

Background:Sulphonylureas are the oldest and commonly used to treat diabetic patients, but its efficacy declines by time. It was reported that quinazoline nucleus exhibits a potent hypoglycemic effect in diabetic animal models.Objective:The current study aimed to synthesize new quinazoline-sulfonylurea conjugates and evaluate their hypoglycemic effects in alloxan-induced diabetic rats.Methods:The conjugates were synthesized by bioisosteric replacement of 5-chloro-2-methoxybenzamide moiety in glibenclamide or 1,3-dioxo-3,4-dihydroisoquinoline moiety in gliquidone with 6,7-dimethoxy-4-oxoquinazoline moiety (compounds 4a-4d, 9b-9c and 10b-10d). Diabetes was induced in rats by a single i.p. administration of alloxan, followed by treatment with the synthesized conjugates (5mg/kg Body weight).Results:All conjugates showed hypoglycemic effects with different efficacy indicated by the reduction in blood glucose and elevation of insulin levels. Moreover, these conjugates up-regulated the expression of pancreatic glucose transporter 2, muscle glucose transporter 4, and insulin receptor substrate-1 genes, compared to the diabetic group. A normal pancreatic tissue pattern was noticed in diabetic rats treated with compounds 9b, 9c, and 10c.Conclusion:Conjugation of sulfonylurea with quinazoline (especially 9b, 9c, 10c) possessed a significant hypoglycemic effect through improving blood insulin level and insulin action and consequently increased the glucose uptake by the skeletal muscles.

Euglycemic Diabetic Ketoacidosis in a Diabetic Patient Treated with SGLT2 Inhibitor

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Lavrynenko O ◽  
◽  
Santos H ◽  
Garza A ◽  
Qazi R ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Diabetic Ketoacidosis ◽  
Glucose Transporter ◽  
Sglt2 Inhibitor ◽  
Anion Gap ◽  
Laboratory Evaluation ◽  
Intravenous Insulin ◽  
Glucose Transporter 2 ◽  
Life Threatening ◽  
History Of

Diabetic Ketoacidosis (DKA) is a life - threatening complication and must be diagnosed and treated promptly and aggressively. The classic triad of DKA is hyperglycemia (Blood Glucose (BG) >250mg/dl; anion gap metabolic acidosis (pH <7.30 and bicarbonate <18mEq/L); and ketonemia. With Food and Drug Administration (FDA) approval of the sodium - glucose transporter 2 inhibitors (SGLT2i), DKA can occur with BG levels below 200mg/dl and has been defined as Euglycemic DKA (EuDKA). Due to the absence of hyperglycemia, the diagnosis of EuDKA is challenging and often delayed. This 60-year-old diabetic male, treated with Empagliflozin and pioglitazone, presented with diarrhea and abdominal pain, which started 20 days ago. He was admitted with dehydration and diagnosis of colitis. On admission laboratory evaluation revealed metabolic acidosis with elevated anion gap of 18mEq/L, bicarbonate of 19mEq/L, and BG of 146mg/dL. There was no history of ingestion of alcohol, salicylates, methanol, ethylene glycol and nothing to suggest lactic acidosis. The plasma creatinine was 0.79mg/dl. On the following day, he developed an increase in the anion gap to 22mEq/L and further decrease in bicarbonate to 13mEq/L, and serum ketones were detected. The patient was treated for EuDKA in ICU with intravenous insulin, dextrose (to prevent hypoglycemia), and normal saline with resolution of his symptoms and EuDKA in 3 days. With the widespread use of SGLT2i, physicians need to have a high suspicion of EuDKA in patients who present with an unexplained anion gap acidosis without or only modest elevation in BG concentration.

scholarly journals Molecular Mechanisms of SGLT2 Inhibitor on Cardiorenal Protection

2020 ◽  
Vol 21 (21) ◽  
pp. 7833
Author(s):  
Yi-Chou Hou ◽  
Cai-Mei Zheng ◽  
Tzung-Hai Yen ◽  
Kuo-Cheng Lu
Keyword(s):  
Diabetes Mellitus ◽  
Vascular Tone ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Clinical Evidence ◽  
Sglt2 Inhibitor ◽  
Cardiac Protection ◽  
Glucose Transporter 2 ◽  
Glucose Reabsorption ◽  
Molecular Aspects

The development of sodium-glucose transporter 2 inhibitor (SGLT2i) broadens the therapeutic strategies in treating diabetes mellitus. By inhibiting sodium and glucose reabsorption from the proximal tubules, the improvement in insulin resistance and natriuresis improved the cardiovascular mortality in diabetes mellitus (DM) patients. It has been known that SGLT2i also provided renoprotection by lowering the intraglomerular hypertension by modulating the pre- and post- glomerular vascular tone. The application of SGLT2i also provided metabolic and hemodynamic benefits in molecular aspects. The recent DAPA-CKD trial and EMPEROR-Reduced trial provided clinical evidence of renal and cardiac protection, even in non-DM patients. Therefore, the aim of the review is to clarify the hemodynamic and metabolic modulation of SGLT2i from the molecular mechanism.

scholarly journals The Role of SGLT2 Inhibitor on the Treatment of Diabetic Retinopathy

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Wenjun Sha ◽  
Song Wen ◽  
Lin Chen ◽  
Bilin Xu ◽  
Tao Lei ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Glucose Transporter ◽  
Early Stage ◽  
Sglt2 Inhibitor ◽  
Research Field ◽  
Research Progress ◽  
Diabetic Microangiopathy ◽  
Control Blood Glucose ◽  
Glucose Transporter 2 ◽  
Prevention And Treatment

Diabetic retinopathy (DR) is one of the most serious complications of diabetic microangiopathy. DR has an early onset and is not easy to detect. When visual impairment occurs, the optimal period for therapy is often missed. Therefore, the prevention and treatment of DR should start from the early stage of diabetes. Sodium-dependent glucose transporter 2 inhibitor (SGLT2i) is a new antidiabetic drug which is mainly used in clinical practice to control blood glucose of patients with type 2 diabetes prone to develop chronic heart failure. Recent studies have found that SGLT2 is also expressed in the human retina. Now, the prevention and treatment of diabetic retinopathy with SGLT2i while reducing blood sugar has become a new research field. Hence, this article reviewed the recent therapeutic and research progress of SGLT2 in the treatment of diabetic retinopathy.

scholarly journals Effects of GLP-1RA and SGLT2i, Alone or in Combination, on Mouse Models of Type 2 Diabetes Representing Different Disease Stages

2021 ◽  
Vol 22 (21) ◽  
pp. 11463
Author(s):  
Masao Koike ◽  
Hitoki Saito ◽  
Genta Kohno ◽  
Masahiro Takubo ◽  
Kentaro Watanabe ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Fatty Liver ◽  
Glucose Transporter ◽  
Hepatic Lipid Accumulation ◽  
Beneficial Effects ◽  
Glucose Transporter 2 ◽  
Combined Use ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 receptor agonist (GLP-1RA) and sodium-dependent glucose transporter 2 inhibitor (SGLT2i), in addition to lowering glucose, have pleiotropic effects on the heart, kidneys, and liver. These drugs have thus come into widespread use for treating type 2 diabetes (T2DM). However, mechanistic comparisons and effects of combining these drugs have not been adequately studied. Employing diet-induced obese (DIO) mice and db/db mice as models of the early and advanced stages of T2DM, we evaluated effects of single or combined use of liraglutide (a GLP-1RA) and ipragliflozin (a SGLT2i). Treatments with liraglutide and/or ipragliflozin for 28 days improved glycemic control and reduced hepatic lipid accumulation similarly in DIO mice. In contrast, in db/db mice, despite similar favorable effects on fatty liver, liraglutide exerted no beneficial effects on glycemic control. Improved glycemic control in db/db mice treated with ipragliflozin was accompanied by increased pancreatic β-cell area and insulin content, both of which tended to rise further when ipragliflozin was combined with liraglutide. Our data suggest that liraglutide is more efficient at an earlier stage and ipragliflozin can be effective in both stages. In addition, their combined use is a potential option for treating advanced stage diabetes with fatty liver disease.

scholarly journals Euglycemic Diabetic Ketoacidosis in Concurrent Very Low-carbohydrate Diet and Sodium-glucose Transporter-2 Inhibitor Use: A Case Report

2020 ◽  
Vol 4 (2) ◽  
pp. 185-188
Author(s):  
Matthew Earle ◽  
Brian Ault ◽  
Caitlin Bonney
Keyword(s):  
Case Report ◽  
Diabetic Ketoacidosis ◽  
Weight Control ◽  
Glucose Transporter ◽  
Diabetic Patients ◽  
Low Carbohydrate Diet ◽  
Ketogenic Diets ◽  
Glucose Transporter 2 ◽  
Low Carbohydrate ◽  
Euglycemic Diabetic Ketoacidosis

Introduction: With the incredibly high incidence of Type 2 Diabetes in the current population of emergency department patients, it is critical for clinicians to understand the possible complications of the treatment of this disease. Medication like canagliflozin are more common to encounter on patient’s home medication lists and clinicians should be aware of how these medications, alone or combined with dietary modifications, can result in significant pathology and even mortality if not appropriately treated. Case Report: We report a case of a patient with type II diabetes mellitus who presented with euglycemic diabetic ketoacidosis in the setting of concurrent use of canagliflozin, a sodium-glucose transporter-2 (SGLT-2) inhibitor, and strict adherence to a low-carbohydrate ketogenic diet for weight control. Discussion: Euglycemic ketoacidosis has previously been observed in both diabetic and non-diabetic patients following strict ketogenic diets, as well as in diabetic patients being treated with SGLT-2 inhibitors. Conclusion: As more patients choose ketogenic diets for weight control and diabetes management, clinicians should be aware of this potentially life-threatening complication in patients concurrently taking SGLT-2 inhibitors.

scholarly journals The residual cardiorenal risk in type 2 diabetes

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Dario Giugliano ◽  
Maria Ida Maiorino ◽  
Giuseppe Bellastella ◽  
Katherine Esposito
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Glucose Transporter ◽  
Major Adverse Cardiovascular Events ◽  
World Population ◽  
Dipeptidyl Peptidase 4 ◽  
Cardiovascular Outcome Trials ◽  
Glucose Transporter 2 ◽  
Dipeptidyl Peptidase 4 Inhibitors

AbstractIn this commentary, we introduce the concepts of removed and residual risks in conditioning thecardiorenal outlook of patients with type 2 diabetes (T2D). The removed cardiorenal risk represents the risk of progression of CV events (major adverse cardiovascular events, MACE; heart failure, HF) and diabetes kidney disease (DKD) taken away by optimal glycemic control or the use of newer antihyperglycemic drugs (glucagon-like peptide-1 receptor agonists, GLP-1RA, andsodium-glucose transporter-2 inhibitors, SGLT-2i) in patients with T2D, as demonstrated by the results of intensive glucose lowering trials (IGT) and cardiovascular outcome trials (CVOT). IGT have shown that successful glycemic control has modest benefits, as the removed cardiorenal risk ranges from 9% for MACE, to 20% for progression of DKD and to 0% for HF. The removed risk of MACE is 13% for GLP-1RA and 12% for SGLT-2i. However, SGLT-2i, as compared with GLP-1RA, removed twofold more risk (39% vs 17%) for kidney outcomes and fourfold more risk (33% vs 9%) for HF. Dipeptidyl peptidase-4 inhibitors have no clinically important cardiorenal benefits, as residual risk is 99% for MACE, 100% for kidney outcomes (excluding new albuminuria), and 100% for HF. Although the results of some real world, population-based cohort studies suggest the possibility that the cardiorenal protection afforded by newer antihyperglycemic drugs is additive to that of optimal glycemic control, only specific randomized controlled trials could answer this question.

scholarly journals SGLT2 inhibitors therapy protects glucotoxicity-induced β-cell failure in a mouse model of human KATP-induced diabetes trough mitigation of oxidative and ER stress

2021 ◽  
Author(s):  
Zeenat A. Shyr ◽  
Zihan Yan ◽  
Alessandro Ustione ◽  
Erin M. Egan ◽  
Maria S. Remedi
Keyword(s):  
Er Stress ◽  
Glucose Transporter ◽  
Cell Function ◽  
Cell Mass ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Insulin Content ◽  
Β Cell ◽  
Glucose Transporter 2 ◽  
Β Cell Function

AbstractProgressive loss of pancreatic β-cell functional mass and anti-diabetic drug responsivity are classic findings in diabetes, frequently attributed to compensatory insulin hypersecretion and β-cell exhaustion. However, loss of β-cell mass and identity still occurs in mouse models of human KATP-gain-of-function induced Neonatal Diabetes Mellitus (NDM), in the absence of insulin secretion. Here we studied the mechanisms underlying and temporal progression of glucotoxicity-induced loss of functional β-cell mass in NDM mice, and the effects of sodium-glucose transporter 2 inhibitors (SGLT2i) therapy. Upon tamoxifen induction of transgene expression, NDM mice developed severe diabetes followed by an unexpected loss of insulin content, decreased proinsulin processing and proinsulin accumulation at 2-weeks of diabetes. This was accompanied by a marked increase in β-cell oxidative and ER stress, without changes in islet cell identity. Strikingly, early treatment with the SGLT2 inhibitor dapagliflozin restored insulin content, decreased proinsulin:insulin ratio and reduced oxidative and ER stress. However, despite reduction of blood glucose, dapagliflozin therapy was ineffective in restoring β-cell function in NDM mice when tit was initiated at >40 days of diabetes, when loss of β-cell mass and identity had already occurred. These results have important clinical implications as they demonstrate that: i) hyperglycemia per se, and not insulin hypersecretion, drives β-cell failure in diabetes, ii) recovery of β-cell function by SGLT2 inhibitors is through reduction of oxidative and ER stress, iii) SGLT2 inhibitors revert/prevent β-cell failure when used in early stages of diabetes, but not when loss of β-cell mass/identity already occurred, iv) common execution pathways underlie loss and recovery of β-cell function in different forms of diabetes.

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