Bariatric or metabolic surgery provides superior short and long-term resolution rates in subjects with Type-2 Diabetes Mellitus (T2DM) when compared to intense medical therapy. These resolution rates are more evident for so called “stapling or bypass procedures” such as the Roux-Y Gastric Bypass (RYGB) and the bilio-pancreatic diversion (BPD) with duodenal switch (DS). A recent meta-analysis demonstrated that bariatric surgery, specifically RYGB, was able to decrease insulin requirements by more than 50% in subjects with Type-1 diabetes mellitus (T1DM). These results may encourage us to rethink the patho-physiologic mechanisms of T1DM and elucidate different potential treatment options that may result in insulin independence. In contrast to the most common T2DM, where β-cell dysfunction and insulin resistance play a key role, infusion of adult stem cells with immune-modulatory properties may be of assistance to restore self-tolerance and β-cell mass in T1DM, where autoimmunity is responsible for the selective loss of β-cells. Therefore, we propose a novel hypothesis were metabolic surgery in combination with adult stem cell therapy to promote β-cell regeneration may result in insulin independence in T1DM. To our knowledge and up to date such a hypothesis has not been proposed.