Question

Explain how taking an SGLT-2 inhibitor, along with taking insulin leads to ketoacidosis in people who have Type 2 diabetes. Include all metabolic pathways that are affected, whether directly or indirectly. Also include the organs in which the pathways occur and the hormones that regulate these pathways

Answer 1

SGLT-2 inhibitor (Gliflozins) is used in the treatment of Diabetes Mellitus or Type 2 Diabetes.

These are the medication that has a unique mechanism of lowering blood sugar without taking insulin.

SGLT-2 inhibitor along with taking insulin leads to ketoacidosis in people with Type 2 Diabetes in the following way:

Insulin deficiency leads to reduced glucose utilization and enhanced lipolysis; increased free fatty acids (FFAs) in the liver coupled with high glucagon levels promote FFA oxidation and production of ketone bodies. Thus, in SGLT2-treated type 2 diabetes patients, the lower insulin-to-glucagon ratio stimulates lipolysis augmenting FFA delivery to the liver and resulting in mild stimulation of ketogenesis. If insulin deficiency is more profound, or if carbohydrate availability is drastically restricted, the mild ketosis would evolve toward ketoacidosis.

Metabolic Pathways that are affected are as follow:

Glucose Control: Reduction of HbA1c with SGLT2 inhibitors.

Weight Loss: weight-loss-independent and weight-loss-associated mechanisms contributed to both HbA1c and systolic blood pressure (SBP) lowering with SGLT2 inhibition

Blood Pressure: Reductions in BP are due to the diuretic and volume depletion effects. The longer-term effects are linked to inhibition of the renin-angiotensin system and weight loss.

Lipids: Increase in HDL and LDL cholesterol with no effect on triglycerides.