Comment on Herring et al. Metabolic Effects of an SGLT2 Inhibitor (Dapagliflozin) During a Period of Acute Insulin Withdrawal and Development of Ketoacidosis in People With Type 1 Diabetes. Diabetes Care 2020;43:2128–2136

Bolli, Geremia B.; Porcellati, Francesca; Lucidi, Paola; Fanelli, Carmine G.

doi:10.2337/dc20-2575

Cited by 4 publications

(3 citation statements)

References 5 publications

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“…These findings add to the accumulating data indicating the safety and efficacy of TTP399 for the treatment of T1D. Similar studies have been performed during an inpatient admission, utilizing intravenous insulin to achieve steady state prior to discontinuation of insulin, 11 but have been criticized for failing to model the insulin deficiency that occurs in the everyday lives of people with T1D 14 . Our study was performed in an outpatient clinical trials unit and was designed to mimic acute insulin withdrawal that would occur in the “real‐world”, such as insulin pump failure.…”

Section: Discussionsupporting

confidence: 52%

“…Similar studies have been performed during an inpatient admission, utilizing intravenous insulin to achieve steady state prior to discontinuation of insulin, 11 but have been criticized for failing to model the insulin deficiency that occurs in the everyday lives of people with T1D. 14 Our study was performed in an outpatient clinical trials unit and was designed to mimic acute insulin withdrawal that would occur in the "real-world", such as insulin pump failure. The study design allowed for observation of BHB concentrations across a clinically meaningful spectrum from normal to levels consistent with DKA.…”

Section: Discussionmentioning

confidence: 99%

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Impact of the hepatoselective glucokinase activator TTP399 on ketoacidosis during insulin withdrawal in people with type 1 diabetes

Klein

Boeder

Freeman

et al. 2022

Diabetes Obesity Metabolism

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Aims: To determine the effect of TTP399, a hepatoselective glucokinase activator, on the risk of ketoacidosis during insulin withdrawal in individuals with type 1 diabetes (T1D).Materials and methods: Twenty-three participants with T1D using insulin pump therapy were randomized to 800 mg TTP399 (n = 12) or placebo (n = 11) for 7 to 10 days. After the treatment period, an insulin withdrawal test (IWT) was performed, during which insulin pumps were removed to induce ketogenesis. The IWT was stopped after 10 hours or if blood glucose reached >399 mg/dL [22.1 mmol/L], if beta-hydroxybutyrate (BHB) was >3.0 mmol/L, or for patient discomfort. The primary endpoint was the proportion of participants who reached BHB concentrations of 1 mmol/L or greater.Results: During the 7-to 10-day treatment period, mean fasting plasma glucose was significantly reduced ( À27.6 vs. À4.4 mg/dL [À1.5 vs. À0.2 mmol/L]; P = 0.03) and there were fewer adverse events, including hypoglycaemia, in the TTP399-treated arm. During the IWT, no differences were observed between TTP399 and placebo in mean serum BHB concentration, mean duration of IWT, or BHB at termination of IWT. However, serum bicarbonate was numerically higher and urine acetoacetate was quantitatively lower in the TTP399-treated participants. As a result of higher bicarbonate values, none of the TTP399-treated participants met the prespecified criteria for diabetic ketoacidosis (DKA), defined as BHB >3 mmol/L and serum bicarbonate <18 mEq/L, compared to 42% of placebo-treated participants.Conclusions: When used as an adjunctive therapy to insulin, TTP399 improves glycaemia without increasing hypoglycaemia in individuals with T1D. During acute insulin withdrawal, TTP399 did not increase BHB concentrations and decreased the incidence of DKA.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Impact of the hepatoselective glucokinase activator TTP399 on ketoacidosis during insulin withdrawal in people with type 1 diabetes

Klein

Boeder

Freeman

et al. 2022

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…The prevalence of DKA in COVID-19 patients has been connected to higher severity of death and length of stay in these patients, according to recent review studies published in 2021 33,34 . The case of a patient who presented with COVID-19 symptoms and was later diagnosed with DKA is presented [35][36][37]…”

Section: Discussionmentioning

confidence: 99%

Diabetes Ketoacidosis Is a Cause of Concern in Sodium-Glucose Co-Transporter-2 Inhibitors Medication

Bhasin

Sharma

YADAV

et al. 2022

Int J Life Sci Pharm Res

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Diabetic ketoacidosis (DKA) is a dangerous complication that can afflict persons with Type 1 and Type 2 diabetes and is caused by a lack of glucose utilization and insulin generation. DKA is diagnosed by observing the anion gap values, blood glucose level, pH, serum bicarbonate level, and so on. DKA is associated with an elevated blood glucose of > 250 mg/dl (16.7 mmol/l) and is diagnosed by observing the values of anion gap, blood glucose level, pH, serum bicarbonate level, and so on. It occurs more frequently in type 1 diabetics with low insulin levels. Sodium-glucose Co-transporter-2 (SGLT-2) inhibitors are a novel family of anti-diabetic medications that lower blood glucose levels and produce glucosuria. The US Food and Drug Administration (USFDA) has issued a drug safety warning about the increased risk of DKA when using SGLT-2 inhibitors. Following the USFDA's warning, the European Medicine Agency reported 101 more cases of ketoacidosis caused by SGLT-2 inhibitors in people with Type 2 Diabetes Mellitus (EMA). According to the American Association of Clinical Endocrinologists, all SGLT-2 inhibitors should be stopped 3-4 days before major surgery and 24 hours before elective surgery. This review article focuses on the metabolism of ketone bodies and many pathophysiologic mechanisms of SGLT-2 inhibitors, which lower insulin/glucagon ratios, promote glucagon secretion from alpha cells, and increase ketones levels by stimulating lipolysis and resulting in ketogenesis. The primary goal of this study is to improve our understanding of a significant consequence of DKA caused by sodium-glucose cotransporter-2 inhibitors in patients with Type 1 and Type 2 diabetes. Psychosocial factors linked to diabetic ketoacidosis in adults with type 1 diabetes, as well as the prevalence of DKA in COVID-19 patients, have been linked to higher severity of mortality and duration of stay in these patients, according to recent research.

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Insulin therapy: a century of continuing progress

Bolli,

Fanelli,

Lucidi

et al. 2023

Insulin

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Comment on Herring et al. Metabolic Effects of an SGLT2 Inhibitor (Dapagliflozin) During a Period of Acute Insulin Withdrawal and Development of Ketoacidosis in People With Type 1 Diabetes. Diabetes Care 2020;43:2128–2136

Cited by 4 publications

References 5 publications

Impact of the hepatoselective glucokinase activator TTP399 on ketoacidosis during insulin withdrawal in people with type 1 diabetes

Impact of the hepatoselective glucokinase activator TTP399 on ketoacidosis during insulin withdrawal in people with type 1 diabetes

Diabetes Ketoacidosis Is a Cause of Concern in Sodium-Glucose Co-Transporter-2 Inhibitors Medication

Insulin therapy: a century of continuing progress

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