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临床试验/NCT02075567
NCT02075567已完成不适用

Exercise and Blood Glucose Levels in Patients With Type I Diabetes - a Pilot Study

Medical University of Graz0 个研究点目标入组 7 人开始时间: 2014年1月1日最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
发起方
入组人数
7
主要终点
Number of Participants with no Adverse Events as a Measure of Safety and Tolerability

研究概览

简要总结

Background: During and after exercise there is a twofold stimulation of glucose transporter type 4 in type 1 diabetes mellitus (T1DM) caused by an exogenous insulin injection and muscle contraction. In case of no insulin reduction before exercise and/or an additional carbohydrate supplement patients with T1DM would become hypoglycemic. There are no specific data dependent on individual exercise intensities and strategies of bolus insulin reduction. The aim of the present study is to avoid hypoglycemia during and after exercise and to calculate a critical time where blood glucose would decrease to 50% of baseline by a pre exercise standardized insulin regimen during standardized cycle ergometer exercises dependent on different modes, intensities and energy expenditures as well as counter regulatory hormones.

Methods/design: Participants consist of 7 male subjects aged 18 to 35 years with T1DM (fasting C-peptide (≤ 0.3 nmol/l), HbA1c ≤ 64 mmol/mol). After a four-weeks basal insulin adaptation of ultralong-acting basal insulin (Novo Nordisk) each subject will perform a maximal incremental cycle ergometer exercise test with a reduction of short time insulin of 40% to determine the individual aerobic/anaerobic threshold called first/second lactate turn point (LTP1, LTP2). Four constant load and three high intensity intermittent cycle ergometer exercise tests (30min) will be performed at 5% Pmax below and above LTP1 and LTP2 (at 5% above LTP2 no high intensity intermittent cycle ergometer exercise test) with a reduction of short time insulin doses (standardized breakfast-four hours before each test) of 25% at 5% Pmax below LTP1 and 50% at 5% Pmax above LTP1 and 75% at 5% Pmax below and above LTP2 with one week interception between testing. 24h before testing subjects will be fitted with a continuous glucose monitoring system for at least 48h. Primary outcomes include blood glucose decrease from baseline during constant load tests, energy expenditure during testing, 24h CGMS measurements and hormones catecholamines, cortisol, glucagon and insulin growth factor 1. Secondary outcome measurements include heart rate, lactate and respiratory gas exchange values.

Discussion: If the results confirm the hypothesis, this study could be one of the first recommendations for T1DM patients, how to adapt bolus insulin dose individually before defined exercises without the risk hypoglycemia during and after exercise.

详细描述

1.1. Pathophysiology of type 1 diabetes mellitus

Type 1 diabetes mellitus (T1DM) is an metabolic disease with insulin deficiency and a dysfunctional release of counter regulatory hormone glucagon. In the pathogenesis of T1DM autoantibodies to insulin (IAA), Glutamic Acid Decarboxylase Antibody (GADA) , islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) can be detected. In absence of endogen produced insulin the translocating glucose transporters (GLUT) cannot be activated (excepted insulin insensitive GLUT-2 in liver, β-cells of pancreas, kidneys and small intestine and GLUT-4 while muscle contraction) (Jensen & Richter 2012). The GLUT translocate to the cell surface and import glucose into the cell for metabolism or glycogen storage by glucose-6-phosphatase (G-6-P). For that reason in patients with T1DM exogenous insulin must be injected by intensified insulin therapy or insulin pump therapy. This exogenous insulin docks on the insulin receptor, the insulin receptor substrate (IRS) reacts with G-proteins (guanine nucleotide-binding proteins) on the phosphatidylinositide-3 kinase (PI-3 kinase) and activates GLUT. Furthermore without insulin there is a deficient carbohydrate metabolism while glycogen synthesis, glycogenolysis, gluconeogenesis and glycolysis.

Dependent on dysfunctional insulin release there is also failure in counter regulatory glucagon reaction. In T1DM is no decrease of insulin release while hypoglycemia and thus no increase of α-cell glucagon secretion. So in T1DM there are less endogenous opportunities to avoid hypoglycemia.

1.2. Physiology of type 1 diabetes mellitus in sports

It's already known that in T1DM and non type 1 diabetes mellitus (nT1DM) during and after physical activity the glucose utilization increases. During exercise glucose degradation rate in blood plasma increases by enhanced translocating GLUT-4 through skeletal muscles contractions caused by an increase of calcium (Ca2+), adenosine triphosphate (ATP) turnover, AMP-activated protein kinase (AMPK), founding member of a family of proteins sharing a 180- to 200-amino acid (TBC1D1/4), endothelial nitric oxide synthase (eNOS), p38 mitogen-activated protein kinases (p38 MAPK) and sucrose nonfermenting AMPK-related kinase (SNARK).

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Single Group
主要目的
Health Services Research
盲法
None

入排标准

年龄范围
18 Years 至 35 Years(Adult)
性别
Male
接受健康志愿者

入选标准

  • Subjects must give their signed and dated informed consent before any trial-related activities. Trial-related activities are any procedure that would not have been performed during normal management of the subject
  • Male subjects with T1DM with duration ≥12 month
  • Age ≥ 18 to ≤ 35 years, both inclusive
  • HbA1c ≤ 64 mmol/mol
  • Fasting C-peptide ≤ 0.3 nmol/l
  • Treatment with intensified insulin therapy or insulin pump therapy
  • No diabetic long term complications
  • No other physical and/or mental disease

排除标准

  • Previous participation in this trial
  • History of any illness or disease that, in the opinion of the Investigator might confound the results of the trial
  • Use of drugs, which may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia
  • Current addiction to alcohol or substances of abuse as determined by the investigator
  • Known or suspected allergy to trial products or related products
  • Any condition that the investigator feels would interfere with the trial participation or evaluation of data

结局指标

主要结局

Number of Participants with no Adverse Events as a Measure of Safety and Tolerability

时间窗: 30min

Blood Glucose decrease from baseline during and after constant load and high intensity intermittent cycle ergometer exercise tests before standardized Bolus Insulin regimen

次要结局

  • Hormonal Response(Starting point, middle and End point (30min))

研究者

发起方
Medical University of Graz
申办方类型
Other
责任方
Principal Investigator
主要研究者

Pieber Thomas, MD

Prof. Dr.

Medical University of Graz

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