Clinical trial NCT02498990: Low Calorie Diet and Diabetes
Official title: Long-term Metabol Control After Weight Reduction With Low Calorie Diet in Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Diabetes Mellitus Type 2
Dyslipidemia
Non-alcoholic Fatty Liver Disease
Obesity
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2015-07-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 During the LCD-period, insulin treatment will gradually be reduced and, if possible, withdrawn.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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline in HbA1c (mmol/mol) at 12 and 24 months
timeFrame: 12 months and 24 months
Secondary outcomes:
measure: Change from Baseline in BMI (kg/m2) at 7 weeks, 6,12, and 24 months
timeFrame: 7 weeks, 6, 12 and 24 months
measure: Change from Baseline in Liver Fat (Controlled Attenuation Parameter, db/m) at 7 weeks, 6, 12 and 24 months
timeFrame: 7 weeks, 6, 12 and 24 months
measure: Change from Baseline in Cholesterol (mmo/l) and Triglycerides (mmol/l) at 7 weeks, 6, 12 and 24 months
timeFrame: 7 weeks, 6,12 and 24 months
measure: 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
timeFrame: 7 weeks, 6,12, 24 months
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Karilonska University Hospital
name: Johan Hoffstedt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: