Novel Strategies for Inducing Glycemic Remission during the Honeymoon Phase of Type 2 Diabetes

Two‐year trial of intermittent insulin therapy vs metformin for the preservation of β‐cell function after initial short‐term intensive insulin induction in early type 2 diabetes

“…The strategy of induction and maintenance therapy tested in the present study is fundamentally different from current algorithms for the management of T2DM. First, whereas current approaches focus on limiting glycaemic exposure, the induction/maintenance paradigm targets the reversibility of β‐cell dysfunction (with glycaemic control envisioned as a downstream consequence thereof) . Notably, this study was conducted in a population whose glycaemic control at baseline (mean HbA1c 6.4%) (46 mmol/mol) would not typically precipitate immediate intervention in practice.…”

“…Inclusion criteria included: age 30 to 80 years inclusive; physician‐diagnosed T2DM of ≤5 years’ duration; treatment with either metformin or lifestyle modification only; serum negativity for anti‐glutamic acid decarboxylase antibodies; and screening glycated haemoglobin (HbA1c) concentration between 6.0% and 9.5% (42 and 80 mmol/mol) inclusive if on no antidiabetic medications or between 5.5% and 9.0% (37 and 75 mmol/mol) inclusive if on metformin (recognizing the broad range of glycaemia that may occur in early T2DM because of reversible β‐cell dysfunction) . Exclusion criteria included previous treatment with any antidiabetic medication other than metformin; renal dysfunction (estimated glomerular filtration rate < 50 mL/min); and liver disease or transaminases >2.5‐fold above normal.…”

“…This ongoing need for treatment intensification is ultimately a reflection of the inability of current regimens to prevent the progressive deterioration of pancreatic β‐cell function that characterizes the natural history of T2DM . Although this deterioration has been perceived at times as an inexorable process, it has recently emerged that there is a reversible element to β‐cell dysfunction early in the course of T2DM . Interestingly, it has been known for over two decades that, when administered in early T2DM, a short course of intensive insulin therapy (IIT) for 2 to 3 weeks can have metabolic benefits that persist well after stopping the therapy that can even include the remission of diabetes .…”

“…Historically, the promise of using short‐term IIT in this way eventually gave way to disappointment when it was realized that the remission that it induces is ultimately temporary, as β‐cell function deteriorates over time after the therapy is stopped . In this context, we have proposed that a therapeutic strategy to consider may be the use of short‐term IIT as “induction therapy” to first improve reversible β‐cell dysfunction, followed by a suitable “maintenance therapy” to preserve this beneficial β‐cell effect . With this perspective, we undertook the present study to evaluate the impact on β‐cell function over 2 years of two potential approaches to maintenance therapy: intermittent courses of short‐term IIT administered every 3 months vs daily metformin.…”

Efficacy of short‑term intensive treatment with insulin pump to improve islet β‑cell function in newly diagnosed type 2 diabetes via inhibition of oxidative stress

“…Under high-glucose conditions, the oxidative stress in pancreatic β-cells increases when a series of cytokines and reactive oxygen species (ROS) are released, triggering the activation of death signaling pathways in islet cells (4). However, early islet β-cell dysfunction is partially reversible and early intensive treatment may control blood glucose levels to protect islet β-cells to achieve the goal of improving the prognosis of patients with type 2 diabetes (5,6). Programs for intensive treatment commonly include the use of insulin pumps for continuous subcutaneous infusion of insulin and short-acting pre-prandial insulin may be added as subcutaneous intermediate-acting or long-term insulin as an injection prior to bedtime.…”