scholarly journals Euglycemic DKA in Patients on SGLT2 Inhibitor and Potentially Ketotic State

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A382-A383
Author(s):  
Maram Khalifa ◽  
Hassaan Aftab ◽  
Vitaly Kantorovich
Keyword(s):  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Physical Exam ◽  
Anion Gap ◽  
Type 2 Dm ◽  
Antihyperglycemic Therapy ◽  
History Of ◽  
L 22 ◽  
Beta Hydroxybutyrate

Abstract Background: With mounting evidence demonstrating improved cardiovascular and renal outcomes with the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors, this class of newest antidiabetic agents is rapidly gaining favor. SGLT2 inhibition lowers the renal threshold for glucose excretion, resulting in renal glycosuria, a shift in substrate utilization from carbohydrate to fat oxidation and hyperglucagonemia and thus poses the risk of developing euglycemic DKA as a rare but serious adverse effect. Clinical Cases: the first case is A 36-year-old female was diagnosed with type 2 DM with an HbA1c of 10% and was started on multi-agent antihyperglycemic therapy including metformin 500 mg BID, extended release exenatide 2 mg once a week and empagliflozin 25 mg once daily which were all initiated simultaneously. 2 days after starting regimen, she complained of nausea, vomiting and was unable to tolerate oral diet and fluids by day 4 which potentially predisposed to starvation ketoacidosis. She presented to the ED with normal vitals, grossly normal physical exam and labs were significant for beta-hydroxybutyrate of over 7 mmol/L (ref range <0.28), bicarbonate of 10 mmol/L (22 - 33), anion gap 25 (7 - 17), arterial pH 7.16 (7.33 - 7.43), serum glucose 111 (7.33 - 7.43). GAD-65 antibody titer was <5 IU/mL (< 5). She was diagnosed with euglycemic DKA, transferred to ICU and started on DKA protocol to which she responded very well. Second patient is A 65 Years old male with past medical history of CAD, HTN, HDL, history of PE/DVT and Type 2 DM was on insulin and jardiance, started ketodiet while continuing taking the jardiance and stopped taking his insulin because his sugars were controlled presented to the ED with abdominal pain, nausea and vomiting, had relatively normal vitals and benign physical exam, labs showed Bicarbonate of 9 mmol/L (22 - 33), anion gap of 31 (7 - 17), venous pH of 7.07 (7.33 - 7.43) glucose was 189 (7.33 - 7.43), beta-hydroxybutyrate of over 7.7 mmol/L (ref range <0.28), patient was admitted to the ICU and started on insulin on DKA protocol Conclusion: SGLT2 inhibitors may be associated with DKA due to their ketogenic effects secondary to enhanced lipolysis and increased glucagon to insulin ratio. although not expected, euglycemic DKA could be much more present in cases where there is predisposition to increase ketones generation w/without appropriate clearance eg. starvation, ketotic diet, AKI, etc. These should be monitored for and the patient needs to be educated about accordingly to prevent both adverse outcomes and potential decrease in drug use if not strongly indicated. also,It would be prudent for prescribing clinicians to advise patients to withhold potentially harming medications temporarily if they cannot maintain adequate oral intake.

scholarly journals A Case of Diabetic Ketoacidosis in a Patient on an SGLT2 Inhibitor and a Ketogenic Diet: A Critical Trio Not to Be Missed

2020 ◽  
Vol 2020 ◽  
pp. 1-3 ◽  
Author(s):  
Samantha Steinmetz-Wood ◽  
Matthew Gilbert ◽  
Katherine Menson
Keyword(s):  
Diabetic Ketoacidosis ◽  
Ketogenic Diet ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Anion Gap ◽  
Low Carbohydrate ◽  
History Of ◽  
Ph Level ◽  
Beta Hydroxybutyrate ◽  
Euglycemic Diabetic Ketoacidosis

Results from major clinical trials have shown significant cardiorenal-protective benefits of SGLT2 inhibitors in patients with type 2 diabetes (T2DM), leading to increased popularity. A rare but serious side effect of SGLT2 inhibitors is euglycemic diabetic ketoacidosis (EDKA), which presents more covertly but has been described. Identification and report of modifiable risk factors would be an important step in helping clinicians appropriately counsel patients. In this case report, we present DKA in a patient on an SGLT2 inhibitor and ketogenic diet (KD). A 47-year-old male with a history of poorly controlled T2DM on metformin and empagliflozin presented to the emergency department (ED) with several days of pharyngitis, dyspnea, emesis, abdominal pain, and anorexia. Of note, one month prior to this event, he presented to the ED with malaise and was found to have an anion gap of 21, a bicarbonate level of 13 mmol/L, a pH level of 7.22, 3+ ketonuria, and a glucose level of 7 mmol/L (127 mg/dl). Additional workup was negative, and findings were attributed to his KD. His use of empagliflozin was not identified on his medication list. At second presentation, the patient was tachypneic and tachycardic and had mild abdominal tenderness. Labs revealed anion gap 28, bicarbonate 5 mmol/l, pH 6.94, 3+ ketonuria, glucose 14.9 mmol/L (269 mg/dl), and beta-hydroxybutyrate 8.9 mmol/L. The patient was diagnosed with DKA and was treated accordingly. With closure of anion gap, the patient was transitioned to insulin and metformin, and his empagliflozin was discontinued indefinitely. Before prescribing this medication class, physicians should inquire about low-carbohydrate diets given the higher risk for DKA, though knowledge of this risk is still not widespread.

scholarly journals A Rare Case of Metformin Associated Lactic Acidosis in a Type 2 Diabetic Patient With No Known Contraindications for Metformin Prescription - a Diagnostic Conundrum!

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A361-A362
Author(s):  
Rima Gandhi ◽  
Randa Abdelmasih ◽  
Alauddin El-Hag ◽  
Elis Cruz Salcedo
Keyword(s):  
Lactic Acid ◽  
Metabolic Acidosis ◽  
Lactic Acidosis ◽  
Diabetic Patient ◽  
Side Effect ◽  
Anion Gap ◽  
Type 2 Dm ◽  
History Of ◽  
Type 2 Diabetic

Abstract Introduction: Metformin is a biguanide drug primarily inhibits hepatic gluconeogenesis and improves insulin sensitivity. Lactic acidosis is a rare complication of metformin. The incidence of Metformin-associated lactic acidosis (MALA) is 6.3 per 100,000 patient-years. Metformin raises lactate levels by inhibiting the conversion of lactate and pyruvate into glucose, shunting towards anaerobic glycolysis. Although, MALA is a reported side effect, metformin is still identified as the drug of choice for Type 2 DM. Here we present a case of MALA in a Type 2 Diabetic patient to shed light on this controversial dilemma. Case Presentation: A 56-year-old African-American male with Type 2 DM and diabetic retinopathy presented after a fall and generalized weakness. Upon arrival, his blood sugar was 22 mg/dL. Patient was vitally stable with signs of dehydration. Home medications includes Metformin 1000 mg twice daily and Glipizide. Laboratory results showed an anion gap metabolic acidosis of 18 mmol/L, Lactic acid was 6.5 mmol/L with repeat of 7.6 mmol/L. Creatinine was 6.0 mg/dL with a BUN of 89 mg/dL. Baseline creatinine from 1 year prior was 1.3–1.5 mg/dL with GFR of 52 mL/min. Hemoglobin A1c was 5.9%. Sodium bicarbonate infusion in 5% dextrose in water. The patient clinically improved with closure of the anion gap and resolution of the metabolic acidosis. Metformin level was 10 mcg/mL. He was discharged on basal insulin and discontinued Metformin and Glipizide. Discussion: Metformin is the first line treatment of Type 2 DM due to its safety. The most common adverse events of Metformin include nausea, bloating, and diarrhea. MALA is a rare, yet serious side effect with a reported mortality of 45%. Higher mortality was associated with increased age, lower arterial pH, and need for mechanical ventilation and vasopressor medicationsThe following criteria should raise concern for MALA in patients with history of Metformin use; elevated lactate level, high anion gap, severe acidosis, low serum bicarbonate level and a history of renal insufficiency. Our patient met the above criteria. The treatment approach for MALA includes adequate supportive measures and correction of acidosis with the acceleration of lactic acid metabolism. Ultimately, if there is no improvement with the aforementioned strategies, then the next step is elimination of the offending agent by renal excretion or dialysis. Fortunately our patient improved with intravenous hydration and did not require advanced intervention. This case highlights the importance of the early recognition of MALA in a patient with unexplained anion gap acidosis and history of Metformin use as even with no risk factors, an episode of gastroenteritis can be enough to impair renal function which increases the risk of MALA. More importantly, it is crucial to educate patients to withhold Metformin in the setting of acute illness and volume contraction to prevent MALA.

scholarly journals A Case of Euglycemic Diabetic Ketoacidosis Following Canagliflozin Therapy

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A358-A358
Author(s):  
Kubra M Tuna ◽  
Randa Abdelmasih ◽  
Ramy Abdelmaseih ◽  
Mrhaf Alsamman ◽  
Joseph Robbins
Keyword(s):  
Fatty Acid ◽  
Metabolic Acidosis ◽  
Blood Glucose ◽  
Side Effects ◽  
Diabetic Ketoacidosis ◽  
Sglt2 Inhibitor ◽  
Oral Intake ◽  
Sglt2 Inhibitors ◽  
Anion Gap

Abstract Introduction: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus (DM). In general, DKA characterized by blood sugar over 250 mg/dL, anion-gap metabolic acidosis, and increased plasma or urine ketones. Approximately 2–3% of DKA patients can present with normal blood glucose levels (less than 250 mg/dl) which called euglycemic DKA. Some of the etiologies of euglycemic DKA include recent use of insulin, low caloric intake, alcoholism, chronic liver disease, and pregnancy. Very rarely, SGLT2 inhibitor use may be responsible for euglycemic DKA. Case Presentation: Here we present a case of 44 years old female with a past medical history of DM type 2 who presented with acute onset of nausea and vomiting. Initial laboratory findings were remarkable for anion gap metabolic acidosis with a blood glucose level of 201 mg/dl. The patient was on long-acting insulin along with Canagliflozin and Metformin therapy over years and reported being compliant with medications. She was treated with intravenous insulin therapy which resolved acidosis as well as symptoms. The patient was discharged with recommendations of discontinuation of Canagliflozin. Discussion: SGLT2 inhibitors are the novel class of oral antidiabetic drugs which widely used due to their favorable cardiovascular and renal outcomes independent of glycemic control. However, their side effects remain a concern. DKA is a rare but serious side effect of SGLT2 inhibitors with an incidence rate of 9.4% in type 1 DM and less than 0.2% in type 2 DM. Patients typically present with euglycemia or low-grade hyperglycemia which results in a diagnostic challenge for treating physicians. SGLT2 inhibitors increase urinary glucose excretion with a subsequent decrease in circulating insulin and an increase in glucagon, rendering a metabolic shift from glucose to fatty acid utilization. During times of intercurrent illness (decreased oral intake, sepsis) or metabolic stress (surgery), decreased carbohydrate intake coupled with the aforementioned changes will result in decreased insulin secretion and increased counter-regulatory hormones including adrenaline and cortisol, promoting lipolysis, fatty acid oxidation, and ketone production by the liver which ultimately leading to euglycemic DKA. Conclusion: SGLT2 inhibitors induced euglycemic DKA treatment is identical to classic DKA with consideration of the lack of hyperglycemia. Appropriate patient counseling to ensure safe SGLT2 inhibitor therapy is crucial, including appropriate holding parameters during concomitant volume-depleting illnesses and decreased oral intake. Timely diagnosis of euglycemic DKA, and recognitions of other rare but lethal side effects to decrease overall morbidity and mortality.

scholarly journals Selecting Patients at Risk of Developing DKA on Gliflozins

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A399-A399
Author(s):  
Jelena Maletkovic
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Sglt2 Inhibitors ◽  
The Third ◽  
The Past ◽  
Type 2 Dm ◽  
Oral Antidiabetic ◽  
History Of

Abstract Background: Since the introduction of gliflozins less than a decade ago we have witnessed how these medications are changing our approach to treating patients with type 2 diabetes mellitus. While recognizing tremendous benefits from these medication we are aware of potentially fatal risks. We present three cases of diabetic keto-acidosis in patients with type 2 diabetes mellitus and no prior history of diabetic emergencies while on SGLT2 inhibitors. Cases: A 58 year old woman with history of type 2 diabetes mellitus for 8 years and history of bulimia was treated with an SGLT2 Inhibitor for 12 months with stable control of diabetes mellitus. After an episode of very low calorie diet for 30 hours the patient was admitted to ICU with findings of diabetic ketoacidosis. She was critically ill but responded to treatment and needed only oral medication for future diabetic control. The second patient was a 49 year old man with type 2 diabetes mellitus and obesity who has been treated with oral antidiabetics for 7 years prior to requiring MDI insulin regimen in the past 3 years. The patient was well controlled in the past one year since introduction of SGLT2 inhibitors to his therapy. After a 2 day episode of eating carb heavy diet and using about 20% of prescribed insulin the patient developed DKA and was admitted to ICU where he needed to be intubated but improved and stabilized over the next few days. The third patient was a 52 year old man with history of type 2 DM for 13 years, well controlled in the past 3 years since SGLT2Is were added to his oral antidiabetic therapy. After one night of binge drinking alcohol with poor calorie intake the patient was diagnosed with DKA. After successful treatment this patient remains on oral antidiabetic medications. Conclusion: SGLT2Is have been prescribed in our clinic with great success since the first introduction of these medications. These are the only three patients who developed DKA on SGLT2 inhibitors in the past 6 years to our knowledge. All three patient had risk factors that were recognized but likely not enough emphasized. The first patient developed DKA during a “starvation phase” of eating disorder, the second one during a short episode of non-compliance with insulin while on a high carb diet and the third one after one episode of binging on alcoholic drinks. When prescribing SGLT2 inhibitors we are turning some patients with classical type 2 DM into ketosis prone diabetics. Eating disorders, extremely low or heavy carbohydrate intake, alcohol consumption and non-compliance with other antidiabetic medications should be subjects that we discuss when starting gliflozins in order to avoid significant risks. While using impressive benefits of these medications we should be aware of their side effects and recognize those that are at risk of serious side effects.

scholarly journals How Novel is Dapagliflozin?

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A385-A386
Author(s):  
Shyamsunder Vachhani ◽  
Gautam Das
Keyword(s):  
Type 2 Diabetes ◽  
Emergency Department ◽  
Blood Glucose ◽  
Discharge Planning ◽  
Rare Complication ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Anion Gap ◽  
Diabetes Clinic

Abstract Introduction: Dapagliflozin is one of the novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors and is used in the treatment of patients with type 2 diabetes. Diabetes Ketoacidosis (DKA) is defined by the triad of hyperglycaemia, anion-gap acidosis, and increased plasma ketones. Euglycemic DKA is an uncommon form of ketoacidosis which is characterized by metabolic acidosis with a pH <7.3 and a serum bicarbonate of <18mEq/L, ketosis, and a blood glucose level of <200 mg/dl. This can be caused by SGLT2 inhibitors. Euglycemic diabetes ketoacidosis is a rare complication that occurs in patient taking SGLT2 inhibitors. Here we describe a patient with euglycemic DKA. The incidence of DKA associated with dapagliflozin has been reported to be < 0.1%. Case Presentation: This 55 years old gentleman has past medical history of obesity, type 2 diabetes (since age of 27 yrs.), hypercholesterolemia, hypertension and osteoarthritis. He recently suffered from myocardial infarction discharged 2 days back and presented to emergency department with central chest pain radiating to both arms in the morning. ECG reported as normal and venous blood gas showed pH- 7.10, pCo2- 3.84, pO2- 5.54, glucose- 10, lactate-1.8, bicarbonate- 8.5, base excess 19.2, anion gap 25. And dapagliflozin was stopped as a part of discharge planning and followed up in our diabetes clinic. Urine dipstick revealed Glucose +2, ketone +4, pH 5. He was diagnosed to be suffering from euglycemic diabetic ketoacidosis & treated as per protocol. When he recovered from DKA his insulin was optimised and dapagliflozin was stopped as a part of discharge planning and was followed up in our diabetes clinic. Discussion: In patients on dapagliflozin, cases of euglycemic diabetes ketoacidosis are increasingly being reported. Diagnosis of euglycemic diabetes ketoacidosis can be easily missed in the emergency department due to absence of marked hyperglycemia, often leading to delayed diagnosis and treatment. Mechanism of action of dapagliflozin is by selectively inhibiting the transporter protein SGLT2 in the renal proximal, which prevents glucose reabsorption and subsequently induces the elimination of filtered glucose via urine, the process is known as ‘glycuresis’ which reduces the blood glucose levels. SGLT-2 inhibitors should be initiated by a clinician cautiously and only after adequately weighing the risks and benefits of treatment. It is advisable to do urine test on patient taking dapagliflozin on admission which will help diagnose euglycemic DKA early. To prevent this potentially dangerous complication, patients taking SGLT2 inhibitors who become ill should discontinue the medication, undergo ketone evaluation, and start basal insulin, if ketones are positive. In addition, patients should be educated to stop their SGLT2 inhibitor at least 1 week prior to elective procedures.

scholarly journals AB0420 RISK OF DEVELOPING TYPE 2 DIABETES MELLITUS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1510.2-1510
Author(s):  
L. Kondrateva ◽  
T. Popkova ◽  
E. Nasonov ◽  
A. Lila
Keyword(s):  
Abdominal Obesity ◽  
Lupus Erythematosus ◽  
Antihypertensive Drugs ◽  
Control Group ◽  
Systemic Lupus ◽  
Type 2 Dm ◽  
History Of ◽  
Systemic Rheumatic Diseases ◽  
Very High

Background:Patients with systemic lupus erythematosus (SLE) have higher than in general population prevalence of diabetes mellitus (DM). Hyperinsulinemia is a predictor of developing type 2 DM, however routine measurement of insulin levels for DM risk assessment is uncomfortable in daily clinical practice. International Diabetes Federation recommends the use of patient questionnaires to quickly identify people who may be at a higher risk of DM development.Objectives:To determine the 10-years risk of developing type 2 DM in SLE patients using dedicated questionnaire - Finnish Type 2 Diabetes Risk Assessment Form (FINDRISK) data.Methods:The study included 92 SLE patients without DM (83 women, 9 men, 39 [34; 47] years old). The median disease duration was 6 [2,14] years, SLEDAI-2K was 4[2;8]. SLE pts were treated with glucocorticoids (GC) (89%) and hydroxychloroquine (78%), immunosuppressive drugs (28%) and biological agents (10%). The control group consisted of 88 subjects without systemic rheumatic diseases, inflammatory arthritis or DM, matched by age and sex with SLE patients. Eight items of FINDRISK questionnaire (age, overweight, abdominal obesity, family history of diabetes, physical inactivity, eating habits, history of antihypertensive drugs treatment, history of hyperglycemia) were taken into account to calculate the total risk score (TS). The risk of developing DM within following 10 years is regarded as low (1%) or slightly elevated (4%) with TS ≤11 points, as moderate (17%), high (33%) or very high (50%) with TS ≥12 points.Results:The risk of developing DM was low or slightly elevated in 65 (71%) SLE pts and moderate, high or very high in 27 (29%) pts. The difference was significant compared with the control group, in which 76 (86%) subjects had a low or slightly elevated risk and 12 (14%) had a moderate, high or very high risk (p=0,01). The number of risk factors (4[2;5]) and the median TS of SLE pts (9[5;12] points) were higher than values in control subjects (3[2,4] factors and 6[3;9] points, respectively) (p<0,01 for both). DM risk factors profiles were similar in two groups, except for higher prevalence of abdominal obesity (66% vs 41%, p<0,01) and history of antihypertensive drugs treatment (57% vs 17%, p<0,01) in SLE. There were positive correlations between TS and CRP levels (r=0,25, p=0,02), SLICC (r=0,36, p<0,01), HAQ (r=0,29, p<0,01), and negative correlations between TS and SLEDAI-2K (r= -0,32, p<0,01), glomerular filtration rate by CKD-EPI (r=-0,23, p=0,03). Current GC use had no influence on TS values in SLE.Conclusion:Patients with SLE were more likely than individuals without systemic rheumatic diseases to have a moderate, high and very high risk of developing DM, and therefore, required interventions to prevent the metabolic disease. Increased risk of developing DM was associated with most common traditional factors, especially by abdominal obesity and regular use of antihypertensive drugs that can be considered a kind of equivalent to the presence of hypertension. Curtain contribution of inflammation, lupus activity and irreversible damage index can’t be ignored. Clarification of SLE-specific phenomena in DM pathogenesis requires further research.Disclosure of Interests: :None declared

scholarly journals SGLT2 inhibitors and the risk of diabetic ketoacidosis among adults with Type 2 Diabetes: A systematic review and meta-analysis

2021 ◽  
Author(s):  
Michael Colacci ◽  
John Fralick ◽  
Ayodele Odutayo ◽  
Michael Fralick
Keyword(s):  
Diabetic Ketoacidosis ◽  
Observational Studies ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Controlled Trials ◽  
Absolute Rate ◽  
Randomized Controlled

Importance: The risk of diabetic ketoacidosis (DKA) with sodium-glucose cotransporter-2 (SGLT2) inhibitors is unclear. Objective: To examine the risk of DKA with SGLT2 inhibitors in both observational studies and large clinical trials. Data Sources: Searches of PubMed, EMBASE and CENTRAL (inception to 15 April 2019) without language restrictions; conference proceedings; and reference lists. Study Selection: Randomized controlled trials and observational studies that quantified the rate of diabetic ketoacidosis with an SGLT2 inhibitor in comparison to another diabetes medication or placebo. Data Extraction and Synthesis: Two independent investigators abstracted study data and assessed the quality of evidence. Data were pooled using random effects models with the Hartung-Knapp-Sidik-Jonkman method. Main Outcome and Measures: Absolute event rates and hazard ratios for diabetic ketoacidosis were extracted from each study. Results: Seven randomized trials encompassing 42,375 participants and five cohort studies encompassing 318,636 participants were selected. Among the 7 randomized controlled trials, the absolute rate of DKA among patients randomized to an SGLT2 inhibitor ranged from 0.6 to 2.2 events per 1000 person years. Four randomized trials were included in the meta-analysis, and compared to placebo or comparator medication, SGLT2 inhibitors had a 2.4-fold higher risk of DKA (Relative Risk [RR] = 2.46 [95% CI, 1.16-5.21]; I2 = 0%; P = 0.54). Among the 5 observational studies, the absolute rate of DKA associated with SGLT2 inhibitor use ranged from 0.6 to 4.9 per 1000 person years and a 1.7-fold higher rate of DKA compared to another diabetes medication (RR = 1.74 [95% CI, 1.01-2.93]; I2 = 45%; P = 0.12). Conclusions and Relevance: In adults with type 2 diabetes, SGLT2 inhibitors increase the risk of DKA in both observational studies and large randomized clinical trials. Registration: CRD42019146855 Funding Source: None

scholarly journals Impact of sodium–glucose cotransporter 2 inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease with normoalbuminuria

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Akinobu Nakamura ◽  
Hideaki Miyoshi ◽  
Hiraku Kameda ◽  
Kumiko Yamashita ◽  
Yoshio Kurihara
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Creatinine Ratio ◽  
Sodium Glucose Cotransporter ◽  
Clinical Records

Abstract Background We compared the effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease (CKD) classified by degree of albuminuria. Methods A retrospective review of the clinical records of Japanese participants with type 2 diabetes (age > 20 years; SGLT2 inhibitor treatment > 2 years; estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) was conducted. Based on the urinary albumin-to-creatinine ratio (UACR) or urinary protein-to-creatinine ratio (UPCR) at the start of SGLT2 inhibitor administration, participants were categorized into three groups: normoalbuminuria (A1; UACR < 30 mg/g Cr or UPCR < 0.15 g/g Cr), microalbuminuria (A2; UACR 30 to < 300 mg/g Cr or UPCR 0.15 to < 0.50 g/g Cr), and macroalbuminuria (A3; UACR ≥ 300 mg/g Cr or UPCR ≥ 0.50 g/g Cr). The study outcome was a comparison of the rates of change in renal function evaluated by eGFR at 2 years after starting SGLT2 inhibitor among the three groups. Results A total of 87 participants (40 females, 47 males) were categorized into three groups: A1 (n = 46), A2 (n = 25), and A3 (n = 16). eGFR was similarly decreased at 2 years before starting SGLT2 inhibitor in all three groups. However, the decline in eGFR was ameliorated at 2 years after starting SGLT2 inhibitor, and eGFR was rather increased in the A1 and A2 groups. Interestingly, the rate of change in eGFR at 2 years after starting SGLT2 inhibitor in the A1 group was significantly higher than that in the A3 group. Conclusions These results demonstrate that more favorable effects of SGLT2 inhibitors on renal function were observed in participants with type 2 diabetes and CKD with normoalbuminuria compared with those with macroalbuminuria. Trial registration UMIN-CTR: UMIN000035263. Registered 15 December 2018

scholarly journals Potential Impact on Lipoprotein Subfractions in Type 2 Diabetes

2019 ◽  
Vol 12 ◽  
pp. 117955141986681 ◽  
Author(s):  
Yuka Kamijo ◽  
Hideto Ishii ◽  
Tomohiko Yamamoto ◽  
Kunihisa Kobayashi ◽  
Hiroyuki Asano ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Sglt2 Inhibitor ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
Lipoprotein Subfractions ◽  
Cholesterol Levels

Introduction: Recently, the sodium-glucose cotransporter2 (SGLT2) inhibitor empagliflozin has been shown to lower cardiovascular risk among diabetic patients. It is intriguing that some SGLT2 inhibitors have been found to increase low-density lipoprotein (LDL) cholesterol levels, while the relevance to high-density lipoprotein (HDL) cholesterol is unknown. Although the inhibitory effect of SGLT2 inhibitors on glucose reabsorption may accelerate compensatory lipid metabolism and subsequently reduce body weight and affect the lipid profile, much remains unclear about this mechanism. Therefore, we conducted this study to investigate in detail how canagliflozin affects lipoprotein fractions including LDL and HDL subclasses. Materials and Methods: This study is a multicenter prospective study. The participants were patients with 22 type 2 diabetes (60.7 ± 11.6 years, 59.1% of men) who had HbA1c ⩾ 7.0% and consented to participate in the study. They were administered 100 mg canagliflozin orally once per day. Biochemistry test and cholesterol levels of 20 lipoprotein fractions (G1-G20) using high performance liquid chromatography methods were examined before and after 12 weeks of treatment period. Results: Significant decreases were observed in the participants’ body weight (69.7 to 67.9 kg, P < .001), systolic blood pressure (129.3 to 119.5 mm Hg, P < .01), and HbA1c (8.5% to 7.4%, P < .001). Cholesterol levels in the 20 lipoprotein fractions increased for very large HDL (G14, G15) and large HDL (G16) ( P < .05). Conclusions: Reduction in body weight, improvement of blood glucose levels, and increases in very large HDL and large HDL subclasses were observed after canagliflozin treatment. These beneficial changes might contribute to subsequent suppression of cardiovascular outcomes.

scholarly journals Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Tanaka ◽  
F Soga ◽  
K Tatsumi ◽  
Y Mochizuki ◽  
H Sano ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Function ◽  
Myocardial Function ◽  
Sglt2 Inhibitor ◽  
Left Ventricular ◽  
Sglt2 Inhibitors ◽  
Prospective Multicenter Study ◽  
Lv Diastolic Function

Abstract Background Type 2 diabetes mellitus (T2DM) has come to be considered an independent predictor of mortality, and also a contributor to the development of heart failure (HF) with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Left ventricular (LV) longitudinal myocardial dysfunction as assessed in terms of lower global longitudinal strain (GLS), has been identified even in T2DM patients with preserved LV ejection fraction (LVEF), and should be considered the first marker of a preclinical form of DM-related cardiac dysfunction, leading to HFpEF. Sodium glucose cotransporter type 2 (SGLT2) inhibitors represent a new class of anti-hyperglycemic agents for T2DM, but the effect of SGLT2 inhibitors on LV longitudinal myocardial function in T2DM patients with HF remains uncertain. To examine this effect, as well as the association of LV longitudinal myocardial function with LV diastolic function after administration of SGLT2 inhibitor in T2DM patients with stable HF, we analyzed data from our previous prospective multicenter study, in which we investigated the effect of SGLT2 inhibitor on LV diastolic functional parameters of T2DM patients with stable HF at five institutions in Japan. Methods Our previous trial was a prospective multicenter study of 58 T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least one antidiabetic drugs other than SGLT2 inhibitors started the administration of 5 mg/day of dapagliflozin. Echocardiography was performed at baseline and 6 months after administration of dapagliflozin. LV diastolic function was defined as the ratio of mitral inflow E to mitral e' annular velocities (E/e'). LV longitudinal myocardial function was assessed as GLS based on the current guidelines. Results E/e' significantly decreased from 9.3 to 8.5 cm/s 6 months after administration of dapagliflozin (p=0.020) as previously described, while GLS showed significant improvement from 15.5±3.5% to 16.9±4.1% (p&lt;0.01) 6 months after administration of dapagliflozin. Furthermore, improvement of GLS in HFpEF patients was more significant from 17.0±1.9% to 18.7±2.0% (p&lt;0.001), compared to that in HFrEF patients from 11.3±3.8% to 11.8±4.6% (p=0.13). It was noteworthy that multiple regression analysis showed that the change in GLS after administration of dapagliflozin was the only independent determinant parameter for the change in E/e' after administration of dapagliflozin. Conclusion Dapagliflozin was found to be associated with improvement of LV longitudinal myocardial function, which led to further improvement of LV diastolic function of T2DM patients with stable HF. GLS-guided management may thus lead to improved management of T2DM patients with stable HF. Representative case Funding Acknowledgement Type of funding source: None

Sign in / Sign up

Export Citation Format

Share Document