Healthy Ageing, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia.
Diabet Med. 2021 Sep;38(9):e14564. doi: 10.1111/dme.14564. Epub 2021 Apr 16.
Insulin resistance is an under-recognised metabolic defect and cardiovascular risk factor in Type 1 diabetes. Whether metformin improves hepatic, muscle or adipose tissue insulin sensitivity has not been studied in adults with Type 1 diabetes. We initiated the INTIMET study (INsulin resistance in Type 1 diabetes managed with METformin), a double-blind randomised, placebo-controlled trial to measure the effect of metformin on tissue-specific insulin resistance in adults with Type 1 diabetes.
We will study 40 adults aged 20-55 years with Type 1 diabetes (HbA1c 80 mmol/mol [9.5%], fasting C-peptide <0.3 nmol/L) and 20 age-, gender- and body mass index (BMI)-matched controls. Insulin sensitivity will be determined by the two-step hyperinsulinaemic-euglycaemic clamp method with deuterated glucose to document liver, muscle and adipose insulin sensitivity. Subjects with Type 1 diabetes will be randomised to metformin extended-release 1500 mg daily or matched placebo for 26 weeks. The primary outcome is change in hepatic insulin sensitivity, assessed by change in basal rate of appearance (Ra) of glucose and suppression of endogenous glucose production (EGP) during the low-dose stage of the clamp.
The INTIMET study is the first clinical trial to quantify the impact of metformin on liver, muscle and adipose insulin resistance in adults with Type 1 diabetes. This study may identify factors that predict an individual's response to metformin in Type 1 diabetes.
ACTRN12619001440112.
胰岛素抵抗是 1 型糖尿病中一种未被充分认识的代谢缺陷和心血管危险因素。二甲双胍是否能改善 1 型糖尿病患者的肝、肌肉或脂肪组织胰岛素敏感性尚未在成年患者中进行研究。我们启动了 INTIMET 研究（二甲双胍治疗 1 型糖尿病的胰岛素抵抗），这是一项双盲、随机、安慰剂对照试验，旨在测量二甲双胍对 1 型糖尿病成年患者组织特异性胰岛素抵抗的影响。
我们将研究 40 名年龄在 20-55 岁、1 型糖尿病（HbA1c 80mmol/mol[9.5%]，空腹 C 肽 <0.3nmol/L）且年龄、性别和体重指数（BMI）匹配的对照者。采用两步法高胰岛素-正常血糖钳夹技术联合氘标记葡萄糖来测定肝、肌肉和脂肪胰岛素敏感性，以确定胰岛素敏感性。1 型糖尿病患者将被随机分为二甲双胍缓释片 1500mg 每日组或匹配安慰剂组，疗程为 26 周。主要结局是通过钳夹试验中低剂量阶段葡萄糖基础出率（Ra）和内源性葡萄糖生成（EGP）的抑制来评估肝胰岛素敏感性的变化。
INTIMET 研究是首个在 1 型糖尿病成人患者中量化二甲双胍对肝、肌肉和脂肪胰岛素抵抗影响的临床试验。这项研究可能会确定预测个体对 1 型糖尿病中二甲双胍反应的因素。
ACTRN12619001440112。
