GLYCOGENIC HEPATOPATHY: A COMPLICATION OF UNCONTROLLED DIABETES
OBJECTIVE: To describe a case of hepatomegaly and elevated transaminases in a patient with glycogenic hepatopathy (GH) as a complication of uncontrolled diabetes. METHODS: Clinical, laboratory, and pathological information are described. RESULTS: An 18-year-old male with uncontrolled type 1 diabetes and recurrent diabetic ketoacidosis (DKA) presented with abdominal distention and severe hyperglycemia. Physical examination revealed massive hepatomegaly. Laboratory evaluation showed anion-gap metabolic acidosis, ketonuria, and markedly elevated aspartate and alanine amino transaminases (AST = 1,162 IU/L and ALT = 598 IU/L, respectively). Despite resolution of DKA with insulin infusion, transaminases continued to increase (peak AST = 3,725 U/L, ALT = 1,049 U/L) with no signs of liver failure (normal coagulation profile and albumin level). Abdominal ultrasonography revealed an enlarged liver with moderate echogenicity, consistent with steatosis. Extensive evaluation for causes of hepatitis including toxic, autoimmune, genetic, and infectious diseases was unrevealing. Liver biopsy showed no signs of nonalcoholic fatty liver disease (NAFLD), such as fibrosis, steatosis, or portal inflammation. However, swollen hepatocytes with glycogen accumulation consistent with GH were seen. CONCLUSION: GH can present as hepatomegaly and elevated liver transaminases in patients with uncontrolled diabetes. Clinicians should consider GH in patients with uncontrolled diabetes after ruling out other common causes. Liver ultrasound cannot differentiate this condition from the more commonly seen NAFLD. Although liver biopsy remains a gold standard, evaluation with magnetic resonance imaging may be considered as a less invasive alternative in the appropriate clinical setting.
Expression of angiotensin-converting enzyme 2 and its end product angiotensin 1-7 is increased in diabetic atheroma: implications for inflammation and neovascularization
AIMS: The angiotensin-converting enzyme 2 (ACE2) and its end product angiotensin 1-7 (Ang1-7) are key counterregulatory proteins to offset the deleterious effects of angiotensin II. ACE2 is decreased in diabetic kidney disease but overexpressed in metabolically active atheroma. We tested the hypothesis that ACE2 is increased in diabetic peripheral atheroma, concomitantly with Ang1-7, angiotensin II receptor 1 (AT1R), proinflammatory cytokines, macrophage infiltration, and plaque neovascularization. METHODS AND RESULTS: Peripheral atherectomy plaques collected from 12 diabetic (DM) and 12 non-DM patients were immunostained for ACE2, Ang1-7, AT1R, and proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Macrophage infiltration and neovascularization were counted using double-label immunochemistry with CD68/CD3 and CD34, respectively. Quantification was performed blindly by randomly counting positively stained cells in 20 high-power fields using previously validated methods. Tissue content of ACE2, Ang1-7, and AT1R was increased in DM when compared to non-DM (P<.0001). IL-6 and TNF-alpha were also increased in DM when compared to non-DM (P<.0001), as well as macrophage infiltration score and neovessel counting (P<.0001). CONCLUSION: Expression of ACE2 and its end product Ang1-7 is increased in DM atheroma, along with overexpression of AT1R, IL6, TNF-alpha, macrophage infiltration, and neovascularization. These results suggest that the renin-angiotensin system counterregulatory pathway may be preserved in metabolically active atheroma, offering potential targets for future therapies in diabetic atherosclerosis.