oxyntomodulin and Sepsis

Type 2 diabetes (T2D) is a common comorbidity in people living with HIV (PLWH). Anti-hyperglycemic treatment in PLWH is still a challenge, and no randomized controlled studies using new glucose-lowering agents are currently available.. A 55-year-old-women was admitted to our Diabetes Unit because of hyperosmolar hyperglycemic state (HHS) and sepsis. The medical history included HIV infection and insulin-treated diabetes. On clinical examination, the lady appeared dehydrated with dry buccal mucosa, tachycardia, altered mental status, genital infection, and fever. On admission, plasma glucose was 54.5 mmol/L, HbA1c 155 mmol/mol, osmolarity 389.4 mOsm/kg, bicarbonate 24.6 mmol/L with no detectable serum ketones. The patient was treated with i.v. fluid and insulin, and antibiotic therapy commenced. Upon HHS and sepsis resolution, a basal-bolus insulin therapy was implemented that was followed by significant improvement of daily glucose profiles and progressive reduction of insulin requirement until complete discontinuation. A low dose of metformin plus linagliptin was started. Since a severe atherosclerotic disease was diagnosed, a GLP-1 receptor agonist, dulaglutide, was added to metformin upon linagliptin withdrawal with maintenance of good glycemic control, treatment adherence and amelioration of quality of life and no side effects.. This case suggests that GLP-1 receptor agonist therapy may be effective and safe for treatment of T2D with high cardiovascular risk in PLWH, supporting the need of clinical trials directly assessing the safety and the efficacy of GLP-1 receptor agonist in these individuals.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Glucose; Glycated Hemoglobin; Heart Disease Risk Factors; HIV Infections; Humans; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Insulin; Linagliptin; Metformin; Middle Aged; Quality of Life; Recombinant Fusion Proteins; Risk Factors; Sepsis

We postulate that high plasma concentrations of gastrointestinal-derived glucagon may be used to identify severe sepsis and correlate with the effect of therapy. Eighteen adult dogs were separated into three groups: Group I-LD100 E. coli alone, group II-LD100 E. coli + tobramycin (TOB) and group III-LD100 E. coli + TOB + methylprednisolone sodium succinate (MPSS). E. coli was infused intravenously for one hour. Each animal was monitored for six hours and observed for a 7-day recovery period. Percent survival (greater than 7 days): I = 0%, II = 17% and III = 83%. Concentrations of gastrointestinal glucagon were 3417 pg/ml in group I, 5167 pg/ml in group II and 1081 pg/ml in group III at six hours after E. coli infusion. In group III these concentration returned to control values by 7 days after E. coli infusion. Increases in gastrointestinal glucagon were more readily induced by E. coli infusion than those of pancreatic glucagon. Gastrointestinal glucagon concentrations were related to the severity of E. coli induced shock and the beneficial effects of MPSS/TOB therapy. Therefore, plasma gastrointestinal glucagon concentrations may be useful in recognizing the presence of severe sepsis and directly related to the beneficial effects of therapy.

Topics: Animals; Dogs; Drug Therapy, Combination; Escherichia coli Infections; Gastrointestinal Hormones; Glucagon-Like Peptides; Methylprednisolone Hemisuccinate; Prognosis; Sepsis; Tobramycin