MON-LB110 A Phase 2 Evaluation of a Ready-To-Use Liquid Stable Continuous Subcutaneous Glucagon Infusion for the Treatment of Hypoglycemia Associated Autonomic Failure (original) (raw)
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Medicine
Rationale: Deranged liver function is a common finding among patients with diabetes mellitus. We report a case of liver biopsyproven glycogenic hepatopathy (GH) in a patient with long-standing poorly controlled type 1 diabetes (DM1), presented with recurrent transaminitis. Patient concerns: A 28-year-old Chinese woman was noted to have deranged liver function with transaminases elevated to more than 15 times the upper limit of normal. Diagnosis: She had underlying long-standing poorly controlled DM1. Blood tests including hepatitis serology and autoimmune panel were negative. Liver biopsy confirmed the diagnosis of GH, showing an increase in glycogen deposition with intact liver parenchymal architecture, and no inflammation or significant fibrosis. Interventions: Her glycemic control was optimized. Outcomes: Her transaminase levels normalized upon subsequent follow-up with improved glycemic control. Lessons: GH is suspected when transaminase flare occurs in patients with poorly controlled DM1, usually with exaggerated hemoglobin A1c levels, especially after drug-induced, viral, autoimmune and metabolic liver diseases are excluded. The gold standard of diagnosis is liver biopsy. When diagnosis of GH is ascertained, the mainstay of treatment is to optimize glycemic control. Typically, the transaminases may become normal within days to months after improvement of glycemic control. Compared to non-alcoholic fatty liver disease, GH is associated with favorable prognosis and runs a benign course, making this differentiation clinically important. Abbreviations: ALT = alanine aminotransferase, AST = aspartate aminotransferase, DM1 = type 1 diabetes, GH = glycogenic hepatopathy, HbA1c = haemoglobin A1c, NAFLD = non-alcoholic fatty liver disease, NR = normal range, ULN = upper limit of normal.
Gastroenterologia Japonica, 1989
A cooperative study was conducted to determine the efficacy of one week of treatment with infusion of 1 mg glucagon and 10 units insulin twice daily in severe acute hepatitis. Ninty-eight patients with either prothrombin time less than 60% or thrombotest or hepaplastin test less than 50% of normal were randomly assigned to hormone or placebo treatment. SGOT and SGPT values dropped after treatment with a gradual decrease or increase in total serum bilirubin or cholesterol levels similarly in both groups receiving hormone or placebo. Deranged prothrombin time improved more rapidly in the hormone group than in the placebo group. Glucagon and insulin infusion may stimulate recovery of the liver from injury.
Treatment of fulminant hepatic failure with insulin and glucagon
Digestive Diseases and Sciences, 1991
Fulminant hepatic failure (FHF) is a severe, lifethreatening disorder. Previous studies have suggested that intravenous prostaglandin treatment may improve survival in FHF. The present study was performed to further investigate the possible benefit of intravenous prostaglandin E 1 (PGE 1) for patients with FHF. A total of 18 patients, all excluded as candidates for hepatic transplantation, were studied. Thirteen of 18 participated in a randomized, double-blind, placebo-controlled trial. PGE 1 was administered by continuous infusion at a dose of 10 to 40 g/h as tolerated. After 48 hours of blinded treatment, 3 of 7 patients randomized to placebo were converted to open-label PGE 1 for lack of biochemical and/or clinical improvement. Mean values for alanine transaminase, aspartate transaminase, total bilirubin, prothrombin time, factor V percent, factor VII percent, hepatic encephalopathy score, days from onset of symptoms to initiation of treatment, and cause of FHF were similar between treatment groups. Ten of 18 patients (55%) enrolled in this trial survived. However , survival was not different between PGE 1-(60%) and placebo (50%) treated patients. The greatest predictor of survival was the number of days from onset of symptoms to hospitalization, which was significantly (P ؍ .002) shorter for survivors (3.3 v 12.4 days), regardless of PGE 1 treatment. Six of 8 patients (75%) who began PGE 1 therapy and 4 of 5 placebo-treated patients (80%) hospitalized within 10 days of onset of symptoms survived. By contrast, all 5 patients who were hospitalized and subsequently began PGE 1 treatment 10 days or longer after the onset of symptoms died. We conclude that early recognition and hospitalization is the most important factor in reduction of mortality from FHF. It is unclear whether PGE 1 treatment is beneficial when administered during this period. However, it is apparent that PGE 1 was not effective for treatment of FHF if treatment started more than 10 days after onset of this clinical syndrome.
Case reports in gastroenterology
Glycogen hepatopathy (GH), characterized by reversible transaminitis and hepatomegaly, results from excessive accumulation of glycogen in hepatocytes. GH has been well described in the literature as a rare cause of transaminitis in children and young patients with uncontrolled type 1 diabetes mellitus and has rarely been reported in type 2 diabetic patients. Hyperglycemia and hyperinsulinemia are believed to be a metabolic substrate for hepatic glycogen accumulation and in order to cause glycogen hepatotoxicity. We present the case of a 54-year-old woman with poorly controlled insulin-dependent type 2 diabetes who was hospitalized twice within 1 month with diabetic ketoacidosis/hyperosmolar hyperglycemic state and reversible transaminitis. Interestingly, she had normal liver function tests performed at the time of admission and transaminitis was noted 1 day later, after she was treated with high doses of intravenous insulin therapy. Subsequently, liver enzymes recovered to normal le...
The double glucagon test, a new liver function test
Postgraduate Medical Journal, 1971
Summary A double glucagon test was performed in 100 patients and seventeen control subjects. Two intravenous doses of glucagon (1 mg) were administered at a 1-hr interval. Glucose was determined before the first injection and 20, 25 and 30 min after both doses, and the increases after each successive dose were added up. In normal persons, the total increase in glycaemia was higher in the second than in the first hour and reached at least 110 mg. Normal values were found in cases of obstructive jaundice, cholelithiasis and adult diabetes, and abnormal values in patients with infective hepatitis, liver congestion and cirrhosis. The double glucagon test was found to be very useful for the differential diagnosis of liver cell impairment and hepatic obstruction.
Hypoglycaemia due to Autoimmunity
2022
endocrinologist because of recently discovered symptomatic hyperthyroidism, where T4 and T3 were elevated, TSH was nearly undectable, ultrasound of the neck confirmed diffuse homogenous hypodensity, of the thyroid gland with no retrosternal extension, nuclear scan confirmed uniform uptake of isotope consistent with graves' disease. Antibodies testing showed high Anti-Thyroperoxidase antibodies at 1500 iu/ml (less than 9 iu/ml) TSH receptor antibody was elevated at 130iu/l (1.75iu/l), thyroglobulin antibody (TgAB) 500iu/ml (less than 100 iu/ml), Thyroid stimulating immunoglobulin antibody (TSI) 700%(less than 130%). Hyperthyroidism was confirmed to be due to graves' disease, reexamining the patient revealed early clubbing and pretibial myxedema with no eye signs, patient opted to start on medication and declined radioactive iodine, patient was prescribed Methimazole (Tapazole) 30 mg daily and follow-up with repeat thyroid testing in 8 weeks, Patient improved clinically, repeated thyroid function showed chemical and serological improvement, Methimazole tapered to 15 mg daily, patient discharged back to GP for follow up and follow up with specialist in one year time. Three months later patient experienced a syncopal episode lasted for 10 minutes when she had severe dizziness, sweating and confusion, ambulance was called, blood sugar was 3.5 mmol/L at that time, other vital signs showed blood pressure 130/60, no fever, heart rate 120/min regular, ECG did not show any arrythmia, patient recovered back to normal after given 50ml, 20% dextrose. On arrival to hospital, patient was Asymptomatic with normal vital signs, metabolic panel which included blood sugar, calcium, phosphate, Mg, were all normal, Troponin I and high sensitive troponin were negative, D dimer was negative for her age, CT head was unremarkable, Patient denied taking any medication whether prescribed or from over the counter, CXR was normal, septic screen was ordered. Patient offered to stay overnight in the hospital but she preferred to go home. Two days later patient started to have shaking for one minute and lost consciousness, ambulance was called, Blood sugar found to be 2.5mmol/L, 100 ml 10% dextrose infusion was administered. On arrival to Hospital, patient was almost back to normal, physical examination in ED showed normal vital signs, neurological examination did not show any neurologic deficit, examination of the heart, lung and abdomen were absolutely normal, ECG was sinus with no ST-T changes, urgent CT Head did not show any acute pathology, patient admitted to medical department for more investigation and observation. The following investigations were performed, CXR, X ray abdomen, Full blood count, inflammatory markers, fasting Blood sugar pre-prandial and postprandial blood sugar with breakfast, lunch and dinner, Liver Function tests, metabolic panel, troponin,
Diabetologia, 1979
The portal vein was catheterized via the umbilical vein under local anaesthesia in 10 nondiabetic subjects about to undergo exploratory laparotomy and in 8 patients with liver cirrhosis. Immunoreactive insulin (IRI) and glucagon (IRG) were assayed in portal and peripheral blood before and during IV infusion of glucose (0.33 g/kg) or arginine (25 g). Basal peripheral plasma (IRI) levels were raised in cirrhotic patients (19 + 2 versus 10 _+ I gU/ml; P < 0.001). Basal portal insulin values, however, did not differ in the two groups. After glucose cirrhotic patients had higher peripheral insulin concentrations, compared to controls, significant at 45 and 60 minutes. In contrast portal insulin levels were higher in controls than in cirrhotics by 1 minute (403 + 43 versus 158 • 38 ~tU/ml; P < 0.001) and remained so for the 60 minutes of study. Similarly, after arginine cirrhotics had significantly higher peripheral insulin concentrations and lower portal concentrations than controls. Peak portal vein insulin levels were delayed in cirrhotics (168 __+ 16 ~tU/ml at 3 min) compared with controls (413 + 25 ,uU/ml at 1 min). In the basal state both portal and peripheral glucagon levels were higher in cirrhotics than control subjects. Unlike in controls, 1V glucose did not suppress glucagon secretion in cirrhotic patients. Peripheral plasma glucagon concentrations after arginine were also consistently higher in cirrhotics than controls, but unlike insulin portal venous glucagon levels were also raised (1800 _+ 360 pg/ml, cirrhotics; 960 _+ 87 pg/ml, controls; P < 0.001; 1 min after arginine infusion). We conclude that insulin secretion is decreased in liver cirrhosis and that the peripheral hyperinsulinaemia observed reflects diminished hormone metabolism. The high plasma glucagon levels observed in cirrhotic patients are the result of pancreatic hypersecretion of glucagon.