Individualized Lifestyle Intervention in Subjects With Prediabetes (PLIS)

• ClinicalTrials.gov Identifier: NCT01947595
• Recruitment Status: Completed
• First Posted: September 20, 2013
• Last Update Posted: August 23, 2017
• Sponsor: University Hospital Tuebingen
• Collaborators: German Diabetes-Center, Leibniz-Institut in Düsseldorf; Endocrinology and Metabolic Diseases, Charité Berlin; German Institute of Human Nutrition; University Hospital Carl Gustav Carus; LMU München, medical clinic IV; University Hospital Heidelberg
• Information provided by (Responsible Party): andreas fritsche, University Hospital Tuebingen

Study Description

Brief Summary:

The purpose of this prospective randomized multicenter intervention study is to determine whether in the prevention of Diabetes an intensified lifestyle intervention is superior to a conventional lifestyle intervention in high risk non-Responder subjects. Further, the intensive phenotyping to determine subgroups with an increased risk for diabetes enables an individualized prevention and therapy of type 2 diabetes mellitus.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus Type 2	Behavioral: intensified lifestyle intervention; Behavioral: normal lifestyle intervention; Behavioral: Single lifestyle advice	Not Applicable

Detailed Description:

The study start with an intensive phenotyping at baseline (initial examination) to determine subjects with prediabetes. These high risk non-Responder are randomized in two arms (intensified vs normal lifestyle intervention)with equal number of subjects (n=250). The results are compared with each other at the end of the study.

The low risk Responder are randomized in two arms (normal vs. once lifestyle intervention = control group) with equal number of subjects (n=250).

After the screening at baseline the 12 month lifestyle intervention starts for lifestyle intervention groups. The different therapy groups are formed as described before. The subjects with intensified lifestyle intervention get 16 consultations, the subjects with normal lifestyle intervention get 8 consultations, the subjects of the control group get one consultation to learn more about a healthier lifestyle. During the whole study there is a continuous supervision from physician and nutritional advisers and the subjects have to document a nutrition and an exercise protocol as well as subjective measurements. At baseline, after 24 weeks and at follow up 1, 2 and 3 years later there is an elaborate metabolic characterization of all subjects (also the Responder groups) a 75 g venous oral glucose tolerance test (OGTT) as well as an analysis of the distribution of body fat confirmed by MR-Imaging and proton magnetic resonance spectroscopy by 3 T whole body imager.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1145 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Prediabetes Lifestyle Intervention Study
• Study Start Date: March 2012
• Actual Primary Completion Date: August 2017
• Actual Study Completion Date: August 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: high risk non-responder, intensified lifestyle intervention; high risk non-responder: A) reduced Insulin secretion (disposition index: (IGI * ISI-Matsuda)< 760); B) insulin resistance (ISI-Matsuda < 9,2); C) elevated liver fat ( MRT > 5,56%); A+B or A+C or B+C or A+B+C	Behavioral: intensified lifestyle intervention; physical activity 6 hours per week, 50% guided activity recorded by an accelerometer (Aipermotion 440); 16 sessions per year with a lifestyle advisor nutritional advice (target weight: 5% less, if BMI > 25kg/m², less than 30% fat per caloric intake, less than 10% fatty acids per caloric intake, more than 15 g fibre per 1000 kcl)
Active Comparator: hight risk non responder, normal lifestyle intervention; high risk non-responder: A) reduced Insulin secretion (disposition index: (IGI * ISI-Matsuda)< 760); B) insulin resistance (ISI-Matsuda < 9,2); C) elevated liver fat ( MRT > 5,56%); A+B or A+C or B+C or A+B+C	Behavioral: normal lifestyle intervention; physical activity 3 hours per week recorded by an accelerometer (Aipermotion 440); 8 sessions per year with a lifestyle advisor nutritional advice (target weight: 5% less, if BMI > 25kg/m², less than 30% fat per caloric intake, less than 10% fatty acids per caloric intake, more than 15 g fibre per 1000 kcl)
Active Comparator: Responder, normal lifestyle intervention; Responder: A) reduced Insulin secretion (disposition index: (IGI * ISI-Matsuda)< 760); B) insulin resistance (ISI-Matsuda < 9,2); C) elevated liver fat ( MRT > 5,56%); No A, only B or C	Behavioral: normal lifestyle intervention; physical activity 3 hours per week recorded by an accelerometer (Aipermotion 440); 8 sessions per year with a lifestyle advisor nutritional advice (target weight: 5% less, if BMI > 25kg/m², less than 30% fat per caloric intake, less than 10% fatty acids per caloric intake, more than 15 g fibre per 1000 kcl)
Active Comparator: Responder, single lifestyle advice (control group); Responder: A) reduced Insulin secretion (disposition index: (IGI * ISI-Matsuda)< 760); B) insulin resistance (ISI-Matsuda < 9,2); C) elevated liver fat ( MRT > 5,56%); No A, only B or C	Behavioral: Single lifestyle advice; - Single Health care advice and lifestyle advice (30 minutes) at the beginning; recommend the individual target weight (5% less, if BMI 25> kg/m²)

Outcome Measures

Primary Outcome Measures :

1. postprandial glycaemia (2h plasma glucose level of the 75 g oral glucose tolerance test (OGTT)) [ Time Frame: one year ]

Secondary Outcome Measures :

1. insulin sensitivity confirmed by 75 g oral glucose tolerance test (OGTT) [ Time Frame: one year ]

   insulin resistance is calculated as follows:

   • Insulinogenic index (IGI) = (I30 - I0) / (G30 - G0)
   • ISIest= 10000/²√ ((G0 x I0) x ((G0+G30+G60+G90+G120)/5) x ((I0+I30+I60+I90+I120)/5))
2. insulin secretion confirmed by 75 g oral glucose tolerance test (OGTT) [ Time Frame: one year ]

   insulin resistance is calculated as follows:

   • Insulinogenic index (IGI) = (I30 - I0) / (G30 - G0)
   • ISIest= 10000/²√ ((G0 x I0) x ((G0+G30+G60+G90+G120)/5) x ((I0+I30+I60+I90+I120)/5))
3. distribution of body fat confirmed by MR-Imaging and proton magnetic resonance spectroscopy by 3 T whole body imager [ Time Frame: one year ]

Other Outcome Measures:

1. metabolic and genetic characterization to determine the risk of type 2 diabetes confirmed by case history, clinical examination, venous blood sampling, DNA isolation, standardised questionnaires, bio-electric impedance analysis (BIA)and ergospirometry [ Time Frame: one year ]
2. metabolic and genetic characterization to determine the non-response to lifestyle intervention confirmed by case history, clinical examination, venous blood sampling, DNA isolation, standardised questionnaires,BIA, ergospirometry [ Time Frame: one year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• impaired fasting glucose (IFG)

  • fasting blood glucose 99-126 mg/dl

and/or

• impaired glucose tolerance (IGT)

  • 75 g OGTT 120 minutes: 139-200 mg/dl

Exclusion Criteria:

• current pregnancy or breastfeeding
• BMI > 45 kg/m²
• Diabetes mellitus Typ 1 or 2
• serious disease e.g symptomatic coronary heart disease
• serious symptomatic malignant disease (weight loss > 10% within the last 6 month)
• severe liver or kidney disease ( an increase in transaminases > 3 times than the upper limit of the standardized range, GFR < 50 ml/min/1,73m²)
• systemic infection (CRP > 1 mg/dl)
• severe mental illness
• drug abuse
• treatment with steroids
• potentially incompliant subjects

• exclusion criteria for magnetic resonance tomography

  • any kind of metal in or on the body:

    • cardiac pacemakers
    • prosthetic heart valves
    • metal prosthesis
    • magnetic implanted metallic parts
    • contraceptive coil
    • metal fragments/ grenade shrapnel
    • fixed braces
    • acupuncture needles
    • insulin pump
    • intraport etc.
    • Field strength > 3 Tesla further tattoos, permanent make-up
  • persons with limited thermosensory or heightened sensitivity to heating
  • persons where cardiovascular disease cannot be ruled out by examination
  • persons with heightened sensitivity to loud noise or diseases of the ear
  • used closed whole body scanner: claustrophobia

Additional for spirometry

• acute coronary syndrome
• higher cardiac arrhythmia
• decompensated heart failure
• acute carditis
• pulmonary embolism
• acute deep leg vein thrombosis ( phlebothrombosis)
• hyperthyroidism (TSH)
• hypokalemia

Contacts and Locations

Locations

Germany

Deutsches Institut für Ernährungsforschung / Charité Berlin

Berlin, Germany

University Hospital Dresden

Dresden, Germany

Deutsches Diabetes Zentrum

Düsseldorf, Germany, 40225

Technische Universität München (TU Munich)

Munich, Germany, 80333

Helmholtz Zentrum München

Munich, Germany, 85764

Ludwig-Maximilians-University

Munich, Germany

University Hospital Tübingen

Tübingen, Germany, 72076

Sponsors and Collaborators

University Hospital Tuebingen

German Diabetes-Center, Leibniz-Institut in Düsseldorf

Endocrinology and Metabolic Diseases, Charité Berlin

German Institute of Human Nutrition

University Hospital Carl Gustav Carus

LMU München, medical clinic IV

University Hospital Heidelberg

Investigators

• Principal Investigator: Andreas Fritsche, Prof. Dr. med; University Hospital Tuebingen
• Principal Investigator: Norbert Stefan, Prof.Dr.med.; University Hospital Tübingen

More Information

Additional Information:

Click here for more information about this study: research in the DZD --> klinische Studien 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wagner R, Eckstein SS, Fritsche L, Prystupa K, Horber S, Haring HU, Birkenfeld AL, Peter A, Fritsche A, Heni M. Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health. Front Endocrinol (Lausanne). 2022 Jun 29;13:892677. doi: 10.3389/fendo.2022.892677. eCollection 2022.

Fritsche A, Wagner R, Heni M, Kantartzis K, Machann J, Schick F, Lehmann R, Peter A, Dannecker C, Fritsche L, Valenta V, Schick R, Nawroth PP, Kopf S, Pfeiffer AFH, Kabisch S, Dambeck U, Stumvoll M, Bluher M, Birkenfeld AL, Schwarz P, Hauner H, Clavel J, Seissler J, Lechner A, Mussig K, Weber K, Laxy M, Bornstein S, Schurmann A, Roden M, de Angelis MH, Stefan N, Haring HU. Different Effects of Lifestyle Intervention in High- and Low-Risk Prediabetes: Results of the Randomized Controlled Prediabetes Lifestyle Intervention Study (PLIS). Diabetes. 2021 Dec;70(12):2785-2795. doi: 10.2337/db21-0526. Epub 2021 Sep 16.

• Responsible Party: andreas fritsche, Prof. Dr. med. Andreas Fritsche, University Hospital Tuebingen
• ClinicalTrials.gov Identifier: NCT01947595
• Other Study ID Numbers: DZD-2012
• First Posted: September 20, 2013
• Last Update Posted: August 23, 2017
• Last Verified: August 2017

Keywords provided by andreas fritsche, University Hospital Tuebingen:

diabetes mellitus type 2; impaired glucose tolerance; lifestyle intervention; body fat distribution; prevention

Additional relevant MeSH terms:

Diabetes Mellitus; Prediabetic State; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases