Impact of Body Composition and Exercise on Clinical, Metabolic and Molecular Parameters in Type 2 Diabetics in Qatar

The prevalence of type 2 diabetes (T2DM) is increasing sharply around the world and obesity and sedentary lifestyles are driving the epidemic. Obesity is often, but not always present in patients with T2DM. The primary aim of this study is to understand the impact of the ratio of lean body mass (metabolically active skeletal muscle) to adipose tissue mass on the severity of insulin resistance and pancreatic beta cell dysfunction in non-obese and obese Qatar residents with T2DM. An exercise programme aimed to increase lean mass and aerobic capacity will be initiated for a period 10 weeks in non-obese and obese early onset diabetics who are residents of Qatar. The effect of the exercise programme on total body fat, regional fat distribution and intramuscular and intrahepatic fat content using magnetic resonance imaging (MRI) in these groups of diabetics will be assessed and related to total body insulin sensitivity and β-cell function as measured with the gold standard methods: the euglycemic clamp technique and arginine stimulation. Genetic approaches including candidate gene testing and non-targeted miRNA expression profiling and metabolomics are employed. Physical fitness pre- and post-intervention will also be assessed. The impact of the exercise programme on conventional inflammatory markers, the phenotype of immune cells, metabolic hormones, and markers of oxidative stress, endoplasmic reticulum stress and heat shock response (Hsp-72, Hsp -40/DNAJB3 and Hsp-25) are studied in relation to metabolic changes. Through this study, the contributions of fitness, fatness and exercise training on insulin resistance and beta cell function will be elucidated in Qatari residents with T2DM.


Eligibility Criteria:
Inclusion Criteria:

1. New onset T2DM (\<5 years duration).
2. Aged 18 and 60 years.
3. Residents of Qatar with intention to stay for the duration of the study (approx 4 months)
4. Otherwise healthy or with stable, treated medical conditions (hypertension, hyperlipidemia, hypothyroidism, etc.)
5. Hemoglobin A1c (HbA1c) level \< 8%.
6. "Diet and lifestyle" or metformin or DPP4 inhibitors prescribed for T2DM.
7. Willingness and ability to comply with the exercise protocol and study duration.

Exclusion Criteria:

1. Type 1 Diabetes Mellitus or history of hospitalization for hyperglycemia or suspected ketoacidosis.
2. T2DM prescribed insulin, or any other anti-diabetic agent other than metformin or DDP4 inhibitors.
3. HbA1c ≥8.0%.
4. Body mass index (BMI) ≤ 18.5 kg/m2 (underweight) and ≥ 40 kg/m2 (morbid obese).
5. Reported weight loss or gain (± 2 kg) over the preceding three months;
6. Pregnant or lactating women or women planning to be pregnant during the course of the study.
7. History of regular exercise (the equivalent of 150 minutes of moderate intensity aerobic and/or 2 sessions of resistance training per week) or of a job that demands a similar degree of physical activity within the past 6 months.
8. Use of medications that affect glucose metabolism, glucose tolerance or body weight including oral corticosteroids and atypical anti-psychotics.
9. History of cardiovascular disease including previous myocardial infarction, congestive cardiac failure, valvular heart disease, stroke or the use of medication to alter coagulation including daily aspirin, anti-platelet drugs or any class of anticoagulant or a clinically significant abnormality on electrocardiogram that in the opinion of a consulting cardiologist should prevent participation.
10. History of chronic diseases associated with inflammation and/or the daily use of anti-inflammatory or immunosuppressant medications for arthritis, gout, rheumatologic disorders, inflammatory bowel disease, or viral infections including hepatitis B, C and HIV.
11. History of psychiatric disorders including current clinical depression, schizophrenia, bipolar disorder or subjects with known claustrophobia.
12. History of chronic neurological disorders such as epilepsy, dementia or movement disorders.
13. Hematocrit \<33%.
14. Participation in other research studies that require blood drawing or any medical, nutritional or behavioral intervention.
15. The presence of large ferromagnetic tattoos that may interfere with the MRI determination of body fat.