Diabetes Mellitus

Type 2 diabetes is a global public health crisis that threatens the economies of all nations. There are 2 primary forms of diabetes, insulin-dependent (IDDM) or type-1 and non-insulin dependent (NIDDM) or type-2. In Type-1 DM there is a deficit of insulin caused by autoimmune destruction of β-cells. Therefore the only treatment in the type-1 DM is exogenous administration of insulin or beta cell transplantation. On the other hand in the Type-2 DM, which is also the commonest diabetes phenotype, there is an inherent insulin resistance of peripheral tissues, which indirectly leads to insulin depletion in the latter stages.

Peripheral insulin resistance pervades the glucose entry into tissue resulting in hyperglycaemia. Hyperglycaemia then signals the beta cells to enhance insulin secretion causing a parallel hyperinsulenimia state. This then gradually leads to β-cell exhaustion and dysfunction, and eventually instigates loss of β-cell mass by apoptosis. Recently, de- differentiation of mature insulin-producing β-cells to a “naïve” status has been reported as a novel mechanism of β-cell failure in Type-2 DM. Insulin resistance along with progressive beta cell β-cell failure /depletion may induce uncontrolled hyperglycaemia which does not respond to exogenous insulin. Therefore, although, diabetes is manageable disease and studies have shown that strict blood glucose control decreases the incidence of secondary complications of diabetes, euglycemia is difficult to achieve with current methods of exogenous insulin replacement.

The only definite way to treat Insulin requiring type-2 DM is Langerhans cells transplantation. However, limitations include the short supply of donor of pancreas, the paucity of experienced islet isolation teams, side effects of immunosuppressant, and poor long-term results. Second intriguing possibility is induction of endogenous damaged beta cells.

The field of regenerative medicine has rapidly evolved, paving the way for novel therapeutic interventions through cellular therapies and tissue engineering approaches. The remarkable plasticity of different cell subsets obtained from human embryonic and adult tissues from disparate sources (including bone marrow, umbilical cord, amniotic fluid, placenta, and adipose tissue) has sparked research endeavours evaluating use of these cells for numerous conditions such as graft versus host disease, and immunological inflammatory diseases of nervous system, CVS and GIT. Its role in management of diabetes and its complications also seems to be promising. Human clinical trials have shown that stem cells can result in significant decrease in the insulin dose requirement along with improvement in the stimulated C-peptide levels in type 2 diabetes mellitus.

In our present study, we want to evaluate the safety and efficacy of autologous bone marrow derived stem cells after super selective intra-arterial implantation in gastro duodenal artery through trans femoral route in patients with Type 2 Diabetes.

Assessment of treatment safety will be based on incidence of any treatment emergent/treatment associated adverse events prior to discharge and at 1, 3, 6 and 12 months post Stem Cell therapy.

Changes in Insulin requirement, fasting C-peptide, glucagon stimulated C-Peptide and glycosylated haemoglobin will be evaluated for assessment of efficacy of treatment.

Insulin requirement: Change in Insulin requirement will be evaluated as more than 50 % reduction in dose of insulin from the insulin dose before the stem cell therapy and at 1, 3, 6 and 12 months post Stem Cell therapy.

C-peptide: This is commonly used in preference to insulin measurement when assessing β-cell function in clinical practice. In patients on insulin, C-peptide measurement is better marker of actual production of insulin by beta cells. To measure beta-cell function, the C peptide will be measured 15 minutes before, just before and 6 minutes after intravenous administration of 1 mg glucagon injection. C-peptide measurement will be done 1, 3, 6 and 12 months post Stem Cell therapy. Measurement of C-peptide will indicate how well your beta cells have revived after treatment.

Glycosylated Haemoglobin: Change in HbA1c as compared to baseline at the end of 1, 3, 6 and 12 months of Stem Cell therapy. Glycosatedhaemoglobin will indicate the diabetes control levels.
Lipid levels: Change in lipid levels as compared to baseline at the end of 1, 3, 6 and 12 months of Stem Cell therapy

We will be treating your Diabetes from mononuclear fraction stem cells derived from the bone marrow taken from iliac crest. There is enough evidence to show that super selective administration of bone marrow derived mononuclear fraction has potential to reverse uncontrolled diabetes. Treatment can be either done in India or Trinidad.

We will be doing femoral catheterization and super selective intra-arterial injection of bone marrow derived mononuclear cells into gastro duodenal artery.

The treatment length would be as follows: Intra-arterial injection of bone marrow derived stem cells once with follow-up of another 7 days as direct observation before the discharge.

Our staff members will follow you up in accordance to the study protocols. Each study protocol will be discussed with you. We will also collaborate with your diabetologist to monitor your blood sugar levels and titrate your Insulin requirement to ensure optimal glucose control. Our medical staff will be monitoring your insulin, C-peptide, glycosylated haemoglobin and lipid levels at 1, 3, 6 and 12 months after treatment.