Effects of Metformin Therapy on Pancreatic and Hepatic Fat Content in Patients of Type 2 Diabetes Mellitus
Condition: Type2diabetes
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      A sample size of 15 patients with T2DM visiting Fortis C DOC Hospital will be recruited with
      informed, written consent and will be requested to answer a validated questionnaire in a
      language known to them (English/Hindi). All these patients will undergo 2 weeks diet and
      exercise run in period using standard guidelines. Clinical details will be obtained from the
      case records of the patients. Anthropometry, skinfolds & blood pressure will be recorded as
      mentioned in previous studies from our group (see below for details)18,19. Overweight and,
      obesity will be defined according to predefined guidelines for Asian Indians20. Abdominal
      obesity is defined as waist circumference of ≥ 90 centimetres (cms) in males and ≥ 80 cms in
      females21. Each eligible subject will undergo ultrasonography of liver and pancreas before
      recruitment. Following ultrasonography, patients fulfilling the inclusion will be randomised
      to receive the 10 mg of Dapagliflozin as mentioned previously. Biochemistry, ultrasonography,
      DEXA, MRI, will be performed at baseline and at 4 months post intervention.
    

Detailed description: 
      A chronic metabolic disorder described by continuous hyperglycemia we call Diabetes mellitus
      or DM. this metabolic disorder could be for various reasons like resisting to marginal action
      of insulin, also could be due to diminished secretion of insulin, or maybe both. This Chronic
      hyperglycemia could be responsible for other kinds of abnormalities and therefore damage
      various organs in the patient, sometimes this also could even be life threatening
      complications.

      NAFLD (Nonalcoholic fatty liver disease) has the highest incidence rate among obese and
      diabetic patients. In various studies, it has been found that Type 2 diabetes mellitus (T2DM)
      and nonalcoholic fatty liver disease (NAFLD) exist together which is a metabolic disorder. It
      has been found that the occurrence of NAFLD is 59.67% among T2DM patients with nonalcoholic
      steatohepatitis (NASH), simple steatosis (NAFL), and cirrhosis.

      The studies reveal that NAFLD of 70% is usually found among T2DM patients. It is also
      observed that obesity and insulin resistance is correlated with NAFLD.

      Noninvasive assessment and staging of disease are based on clinical parameters such as age,
      sex, liver function test, platelet count, lipid profile, BMI, and imaging modalities such as
      USG, Fibro-scan (FS), and magnetic resonance imaging mass spectroscopy. Such clinical scoring
      systems and TE are useful in the early detection of NAFLD and predicting fibrosis. The
      principle behind the management of NAFLD with T2DM involves an indirect effect through
      improvement in IR and glycemia and thus is used for the treatment of T2DM as well.

      In addition to this, fatty pancreas is gaining importance from the research point of view.
      Study done by our group also showed that subcutaneous and intra-abdominal obesity, including
      fatty liver and pancreatic volume, were larger in non-obese Asian Indians with type 2
      diabetes than in BMI-matched non-diabetic participants, whereas peripheral subcutaneous
      adiposity was lower. A study done in animal model shows that metformin exerted a beneficial
      effect in limiting beta-proliferation caused by high fat diet (HFD) fed to mice and also
      improved insulin resistance. Another study also showed similar effects of Metformin therapy,
      as it decreased the amount of fat in the liver in parallel with an improvement in the
      metabolic parameters and may, thus, be beneficial for preventing the late consequences of
      NAFLD in newly diagnosed diabetic patients.

      The study mentioned below predicted that Metformin would considerably reduce pancreatic and
      liver fat in T2DM patients. Metformin does not appear to cause or exacerbate liver injury
      and, indeed, is often beneficial in patients with nonalcoholic fatty liver disease.
      Nonalcoholic fatty liver frequently presents with transaminase elevations but should not be
      considered a contraindication to metformin use. Literature evidence of liver disease being
      associated with metformin-associated metabolic acidosis is largely represented by case
      reports.

      A recent study from Korea shows that in patients with type-2 diabetes mellitus, the mean
      FIB-4 score increased from 1.38 to 1.51 (p=0.001) after 2 years of metformin therapy, whereas
      the mean HSI score fell from 27.3 to 26.5 (p=0.001).

      While these studies established that hepatic fat and pancreatic volume are high even in
      non-obese patients with T2DM, we were unable to estimate of hepatic and pancreatic fat
      precisely due to non-availability of advanced fat-imaging MRI software.

      Review of Literature: Effects of SGLT2 Inhibitors and Abdominal Adipose Tissue Depots
      Metformin is an effective agent which helps to achieve better blood glucose control. This
      drug also benefits in the reduction of weight and blood pressure. Metformin results in weight
      loss.

      Effect on Fat Mass:

      Apart from weight loss, Metformin has been shown to reduce fat. It was reported that the use
      of Metformin significantly reduces body weight in T2DM patients on metformin therapy and
      inadequate glycemic control.
    

Intervention name(s): Metformin
Intervention type(s): Drug
Intervention description(s): T2DM patients will be provided with metformin in a specified dose
Intervention MeSH terms: Metformin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention