Low Calorie Diet and Diabetes (LCD)

Long-term Metabol Control After Weight Reduction With Low Calorie Diet in Type 2 Diabetes

The primary hypothesis is to investigate whether a low calorie diet for 7 weeks followed by continuous lifestyle advice is an effective option to achieve an improvement in glucose control as measured by HbA1c after 52 and 104 weeks as compared to baseline values in obese type 2 diabetes patients on either tablet or insulin treatment. The secondary hypothesis is to investigate whether the weight reduction therapy also has significant impact on various anthropometric, clinical and metabolic parameters associated with obesity.

Study Overview

• Status: Enrolling by invitation
• Conditions: Obesity; Dyslipidemia; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus Type 2
• Intervention / Treatment: Behavioral: Low calorie diet followed by life style intervention

Detailed Description

This is a prospective study on the impact of low calorie diet followed by a weight maintenance program on 12 and 24 month glucose control in a cohort of patients with obesity and diabetes mellitus. The study will consist of 3 phases:

1. Screening period (up to 12 weeks).
2. Low calorie diet weeks 1-9. Seven weeks of low-calorie diet including 800 kcal/day followed by 2 weeks of gradual introduction of normal diet of eventually 1500-2000 kcal/day, i.e. 600 kcal/day deficit, based on present body weight and sex. At entry of the LCD-period, all medication for diabetes mellitus, with the exception of metformin and insulin, will be removed. During the LCD-period, insulin treatment will gradually be reduced and, if possible, withdrawn. Patients will perform daily self-monitoring of fasting and post-prandial plasma glucose. At each visit, which will take place once a week, the patients will see a physician, a nurse and a dietician. The patients will be given specific advice to increase their physical activity. Patients will remain on medication for dyslipidemia. Blood pressure will be measured at each visit and in case of blood pressure < 110/70 mmHg and/or in case of symptoms associated with hypotension including dizziness, medication for hypertension will be reduced or removed.
3. Weight-maintenance program weeks 10-52.
4. Follow up visits at months 15, 18, 21 and 24.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 14186
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women of age 18-65 years at screening.
2. Diagnosis of type 2 diabetes mellitus.
3. BMI > 30 kg/m2.
4. HbA1c > 52 mmol/mol.
5. Stable weight ± 5% for at least 12 weeks prior to screening.
6. Informed consent must be obtained by each subject before enrollment in the study.

Exclusion Criteria:

1. Pregnant or brest-feeding women or women who are planning to become pregnant or breast-feeding.
2. Type 1 diabetes mellitus or secondary forms of diabetes including pancreatic injury, cushing syndrome etc.
3. Clinically significant diabetic complications
4. Clinically symptomatic gastrointestinal or hepatic disease.
5. History of gastric bypass, antrectomy or small bowel disease.
6. History of pancreatitis.
7. Myocardial infarction within the past six months.
8. Symptomatic ischemic heart disease, heart failure or stroke.
9. Atrial fibrillation.
10. Patients on treatment with warfarin.
11. Diagnosed and/or treated malignancy within the past 5 years.

12. Any of the following laboratory abnormalities at screening:

    • ALT and/or AST > 3 times the upper limit of the normal range.
    • Serum creatinine levels > 130 µmol/l.
    • Clinically significant TSH out of the normal range.
    • Uric acid > 50% above normal level.
13. History of alcohol or other substance abuse within the past 2 years.
14. Psychiatric disease including eating disorder, bulimia nervosa, depression, anxiety, psychotic disease.
15. Potentially unreliable patients and those judged by the investigator to be unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Weight reduction	Behavioral: Low calorie diet followed by life style intervention; Low calorie diet of 800 kcal/day for 7 weeks.; Life style intervention for the remaining study period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in HbA1c (mmol/mol) at 12 and 24 months	12 months and 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in BMI (kg/m2) at 7 weeks, 6,12, and 24 months		7 weeks, 6, 12 and 24 months
Change from Baseline in Liver Fat (Controlled Attenuation Parameter, db/m) at 7 weeks, 6, 12 and 24 months	Liver Fat Measured by Fibroscan	7 weeks, 6, 12 and 24 months
Change from Baseline in Cholesterol (mmo/l) and Triglycerides (mmol/l) at 7 weeks, 6, 12 and 24 months		7 weeks, 6,12 and 24 months
Change from Baseline in 2-hour Glucose (mmol/l) and Insulin (mU/l) by Glucose tolerance test at 7 weeks, 6, 12 and 24 months	Glucose tolerance test: oral administration of 75 g Glucose	7 weeks, 6,12, 24 months

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Investigators: Principal Investigator: Johan Hoffstedt, MD, PhD, Karilonska University Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (ANTICIPATED): February 1, 2024
• Study Completion (ANTICIPATED): August 1, 2025

Study Registration Dates

• First Submitted: July 3, 2015
• First Submitted That Met QC Criteria: July 13, 2015
• First Posted (ESTIMATE): July 15, 2015

Study Record Updates

• Last Update Posted (ACTUAL): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Lipid Metabolism Disorders; Liver Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Liver; Dyslipidemias; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 2015/628-31