Metabolic Phenotyping in Humans (MetPhe)
Metabolic Characterization of Type 2 Diabetic, Obese, Lean Sedentary and Endurance Trained Individuals in Vivo, ex Vivo and in Vitro
調査の概要
詳細な説明
The aim of the present research proposal is to metabolically phenotype endurance trained athletes, lean and obese sedentary and type 2 diabetic individuals with the following objectives:
- assess metabolic flexibility as measured by a euglycemic-hyperinsulinemic clamp
- measure in vivo mitochondrial function by MRS of phosphocreatine (PCr) recovery
- establish primary myoblast cell lines to correlate with the above in vivo measurements, as well as further explore dietary, pharmacological and genetic manipulations in vitro
- quantify intramyocellular lipid (IMCL) and acetylcarnitine in vivo by MRS
Study population:
A total of 132 male participants (18-70 years) will participate in this study. The first group of 33 participants will be lean endurance-trained athletes, the second group will be lean sedentary control participants, the third group will be sedentary type 2 diabetic participants, and the last group of 33 participants will be obese, non-diabetic sedentary control participants. It is preferred to use male participants in order to minimize variation in the measurements by avoiding confounding factors such as hormones.
Main study parameters/endpoints: The main study parameters are differences in metabolic flexibility as measured by euglycemic-hyperinsulinemic clamp, PCr recovery, IMCL and acetylcarnitines as measured by MRS and establishment of primary myoblast cell lines for future use.
研究の種類
入学 (予想される)
連絡先と場所
研究連絡先
- 名前:Madeleen Bosma, M.S.
- 電話番号:31433884254
- メール:m.bosma@maastrichtuniversity.nl
研究連絡先のバックアップ
- 名前:Bram Brouwers, B.S.
- 電話番号:31433884258
- メール:b.brouwers@maastrichtuniversity.nl
研究場所
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Limburg
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Maastricht、Limburg、オランダ、6200MD
- 募集
- Maastricht University
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コンタクト:
- Madeleen Bosma, M.S.
- 電話番号:31433884254
- メール:m.bosma@maastrichtuniversity.nl
-
主任研究者:
- Lauren M Sparks, PhD
-
主任研究者:
- Madeleen Bosma, M.S.
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副調査官:
- Vera Schrauwen-Hindeling, PhD
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
General Inclusion criteria:
- Male sex
- Generally healthy with specifically no known cardiovascular disease or gastric ulcers, which can affect the study parameters
- Stable dietary habits (no weight loss/gain > 3 kg in the last 6 months)
Group 1, type 2 diabetes participants:
- Ages 40-70 years
- BMI > 30 kg/m2
- Non-insulin dependent type 2 diabetes
- Must be on sulphonylurea (SU)-derivate or metformin therapy for at least six months with a constant dose for at least two months, or on dietary treatment for at least six months
- Well-controlled diabetes: HbA1c < 8%
- No diabetes related co-morbidities like cardiovascular diseases, diabetic foot, polyneuropathy, retinopathy
Group 2, obese healthy control participants:
- Ages 40-70 years
- BMI > 30 kg/m2
- A plasma glucose level lower than 6.1 mmol/L
- No family history of diabetes
- No medication use
- Sedentary lifestyle; No participation in any physical activity for at least 2 years
Group 3, endurance trained athletes:
- Ages 18-35 years
- BMI < 25 kg/m2
- No family history of diabetes
- No medication use
- VO2max > 55ml/kg/min
- Active in competitive endurance-exercise activities, 3 times a week for at least 2 years
- Stable level of training for at least 6 months
Group 4, lean healthy sedentary control participants:
- Ages 18-35 years
- BMI < 25 kg/m2
- No family history of diabetes
- No medication use
- VO2max < 55ml/kg/min
- Plasma glucose < 6.1 mmol/L
- Sedentary lifestyle; No participation in physical activity for more than 1 hour per week for at least 2 years
General Exclusion criteria:
- Regular smokers
- Participation in other studies
- Female sex
- Insulin dependent diabetic individuals
- Participants with diabetes related diseases (diabetic foot, diabetic polyneuropathy, diabetic retinopathy etc.)
- Use of Thiazolidines (glitazone/rosiglitazone/pioglitazone/troglitazone)
- Use of anti-coagulants (not thrombocyte-aggregation inhibitors)
- Aberrant ECG (with signs of ischemia or cardiac failure or arrythmias)
- Weight gain/loss > 3 kg in the last 6 months
- HbA1c < 7.8 in type 2 diabetic individuals
Contraindications for MRS scans:
- Electronic implants such as pacemakers or neurostimulator
- Iron-containing foreign bodies in eyes or brain
- Some hearing aids and artificial (heart) valves which are contraindicated for MRS
- Claustrophobia
- Participants, who do not want to be informed about unexpected medical findings, or do not wish that their physician be informed, cannot participate in the study.
研究計画
研究はどのように設計されていますか?
デザインの詳細
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Euglycemic-hyperinsulinemic clamp for measurement of insulin sensitivity and metabolic flexibility
時間枠:10 hours
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After taking fasting blood samples, a primed constant infusion of glucose is initiated.
Plasma glucose levels are clamped at ~5 mmol/L by variable co-infusion of 20% glucose.
Every 5 minutes, blood is sampled for immediate determination of plasma glucose concentration.
Glucose infusion rate is adjusted to obtain plasma glucose levels of ~5 mmol/L (euglycemia).
A bolus of insulin is then infused.
Before and during steady state, substrate oxidation is measured using an indirect calorimeter, which determines metabolic flexibility.
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10 hours
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Evaluating mitochondrial function through measurement of phosphocreatine (PCr) recovery by phosphorus magnetic resonance spectroscopy (31P-MRS) within the skeletal muscle
時間枠:1.5 hours
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The quantification of energy metabolites (Pi, PCr and ATP) in skeletal muscle will be performed in the v. lateralis at rest, during submaximal knee-extension exercise and during recovery.
The rate at which PCr concentration is restored after exercise is an excellent in vivo measure of skeletal muscle mitochondrial oxidative capacity.
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1.5 hours
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協力者と研究者
捜査官
- スタディディレクター:Patrick Schrauwen, PhD、Maastricht University
- 主任研究者:Lauren M Sparks, PhD、Maastricht University
- 主任研究者:Madeleen Bosma, M.S.、Maastricht University
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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