Individualized Lifestyle Intervention in Subjects With Prediabetes (PLIS)

Prediabetes Lifestyle Intervention Study

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus Type 2
• Intervention / Treatment: Behavioral: intensified lifestyle intervention; Behavioral: normal lifestyle intervention; Behavioral: Single lifestyle advice

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 Type: Interventional
• Enrollment (Actual): 1145
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Deutsches Institut für Ernährungsforschung / Charité Berlin
  • Dresden, Germany
    • University Hospital Dresden
  • Düsseldorf, Germany, 40225
    • Deutsches Diabetes Zentrum
  • Munich, Germany, 80333
    • Technische Universität München (TU Munich)
  • Munich, Germany, 85764
    • Helmholtz Zentrum München
  • Munich, Germany
    • Ludwig-Maximilians-University
  • Tübingen, Germany, 72076
    • University Hospital Tübingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / 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 activityrecorded by an accelerometer (Aipermotion 440); 16 sessions per year with a lifestyle advisornutritional 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 weekrecorded by an accelerometer (Aipermotion 440); 8 sessions per year with a lifestyle advisornutritional 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 weekrecorded by an accelerometer (Aipermotion 440); 8 sessions per year with a lifestyle advisornutritional 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
postprandial glycaemia (2h plasma glucose level of the 75 g oral glucose tolerance test (OGTT))	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
insulin sensitivity confirmed by 75 g oral glucose tolerance test (OGTT)	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))	one year
insulin secretion confirmed by 75 g oral glucose tolerance test (OGTT)	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))	one year
distribution of body fat confirmed by MR-Imaging and proton magnetic resonance spectroscopy by 3 T whole body imager		one year

Other Outcome Measures

Outcome Measure	Time Frame
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	one year
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	one year

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Collaborators: University Hospital Heidelberg; University Hospital Carl Gustav Carus; German Institute of Human Nutrition; German Diabetes-Center, Leibniz-Institut in Düsseldorf; Endocrinology and Metabolic Diseases, Charité Berlin; LMU München, medical clinic IV
• Investigators: Principal Investigator: Andreas Fritsche, Prof. Dr. med, University Hospital Tuebingen; Principal Investigator: Norbert Stefan, Prof.Dr.med., University Hospital Tübingen

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): August 1, 2017
• Study Completion (ACTUAL): August 1, 2017

Study Registration Dates

• First Submitted: June 25, 2013
• First Submitted That Met QC Criteria: September 17, 2013
• First Posted (ESTIMATE): September 20, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 23, 2017
• Last Update Submitted That Met QC Criteria: August 22, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: prevention; lifestyle intervention; diabetes mellitus type 2; impaired glucose tolerance; body fat distribution
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Prediabetic State
• Other Study ID Numbers: DZD-2012