In the pathogenesis of type 1 diabetes, not only insulin hormone deficiency but also inappropriate secretion of counterregulatory hormones are thought to play a part. From this point of view, inhibition of counterregulatory hormones should also be evaluated in the treatment of type 1 diabetes. The cyclic tetradecapeptide hormone somatostatin was first characterized as the major physiological inhibitor of growth hormone release from the pituitary, but it has subsequently been shown to inhibit the release of many other physiologically important compounds, including insulin, glucagon, gastrin, and secretin. Diabetic ketoacidosis (DKA) is a complication of type 1 diabetes, and its management includes insulin, fluid, and electrolyte therapy. Alternative treatments have been investigated in unresponsive patients. As a inhibiting hormone of counterregulatory hormones, somatostatin may be used in the treatment of diabetic ketoacidotic coma. In this study, two diabetic ketoacidotic children who were unresponsive to standard insulin and fluid therapy are discussed; despite appropriate management of fluid and electrolytes, the patients’ blood glucose levels could not be lowered, and they had no clinical improvement. We tried somatostatin infusion therapy in both of these children.

The first patient is an 8-year-old girl who was admitted to our emergency room with a history of polyuria and polydipsia during the last week. She had deep and rapid breathing, loss of consciousness, and acidosis at the time of admission. There was no particular disease in her personal or family history. On physical examination, tachicardia and Kussmaul breathing were present, and severe dehydration was observed. The Glasgow coma scale was 3, with unresponsiveness to either verbal or pain stimulus and loss of consciousness. Leukocytes were markedly increased at peripheral blood smear. Microscopic and bacteriologic examination of urine was normal, but glucose and acetone in urine were quite highly positive. The blood glucose concentration was 1,300 mg/dl. The patient was hospitalized for management of DKA.

The second patient was an 11-year-old boy who had prior complaints of polyuria and polydipsia for the previous 10 days. He was admitted with loss of consciousness, deep and rapid breathing, and acidosis. There was no particular disease in his past or family history. On physical examination, tachicardia and Kussmaul breathing were present, and severe dehydration was observed. The Glasgow coma scale was 3 at admission, with unresponsiveness to either verbal or painful stimulus and loss of consciousness. A peripheral smear revealed markedly increased leukocytes. Microscopic and bacteriologic examination of urine was normal, but glucose and acetone in urine was quite high. The blood glucose level was 1,300 mg/dl, and the other biochemical parameters were in the normal range. The patient was diagnosed as having diabetic ketoacidotic coma and hospitalized.

As the initial therapy, we started 100% oxygen inhalation by face mask and an infusion of 0.9% normal saline (10 ml/kg over 30 min), which was repeated twice. The deficit and maintenance fluids were calculated for fluid treatment (deficit fluid was calculated as the estimated percent dehydration times body weight; maintenance fluid was 60 ml/kg per 24 h in patient 1 and 50 ml/kg per 24 h in patient 2). We then added deficit fluids to 48-h maintenance fluids and replaced this volume over 48 h with 0.9% normal saline. We added 40 mmol/l potassium chloride to each liter of saline infusion. Bicarbonate was not used during the therapy. Insulin was started until shock was successfully reversed and saline/potassium rehydratation regimen was begun. Insulin therapy was started as continuos low-dose intravenous infusion (0.1 units/kg per h). Although sufficient fluid and insulin infusion was begun, the patients did not recover. The total insulin dose was increased by 25%, but in patient 1, at the 20th hour of treatment, blood glucose could not be lowered under 800 mg/dl, and she was still unconscious. In patient 2, at the 15th hour of treatment, blood glucose could not be lowered under 500 mg/dl, and he was also unconscious at that time. Meanwhile, pH was found to be 7.31 and 7.30 in patients 1 and 2, respectively. We have documented that there was no brain edema, electrolyte imbalance, or central nervous system (CNS) infection. Therapy steps were reevaluated for probable mistakes, and the therapy was found to be normal. We started continuous 3.5 μg/kg per h somatostatin asetat (250-μg ampule Stilamin; Serono) infusion. In patient 1, blood glucose dropped to 400 mg/dl, and she regained conscious 4 h after the beginning of somatostatin infusion. In patient 2, blood glucose dropped to 300 mg/dl, and he was conscious 3 h after the beginning of somatostatin infusion. When the blood glucose fell to 270 mg/dl, the infusion was changed to 0.45% saline with 5% glucose. When oral fluids were tolerated and insulin doses were decreased to <0.05 units/kg per h, the insulin infusion and fluid therapy were stopped, and we started subcutaneous insulin therapy. The patients were discharged after completion of therapy and followed-up at our outpatient clinics.

Somatostatin analogs have been used in the treatment of neuroendocrine tumors, vipomas, carcinoid tumors, congenital microvillus atrophy, AIDS-associated diarrhea, gastrointestinal system bleeding, dawn phenomena, and short-small bowel syndrome. The use of somatostatin in type 1 diabetes is not a new phenomenon. Somatostatins have been successfully used in the treatment of diabetes-associated autonomic neuropathy, and they have also been shown to decrease the requirements for insulin (1,2). This effect is via inhibition of ketogenesis and decreasing secretion of glucagon (3). In the literature, there are limited studies about somatostatin use in DKA. It was used in unresponsive and glucagonoma-caused diabetic ketoacidotic coma (4), and it was also used prophylactically in the short term for patients at risk of DKA (3). Yun et al. (5) compared insulin with somatostatin analogs and insulin therapy in DKA. The improvement in hyperglycemia and acidosis was not different, but in the somatostatin-added group, improvement in ketonuria was achieved earlier. The authors concluded that somatostatin analogs were not effective in manifest DKA to control acidosis and hyperglycemia. In a study by Greco et al. (6), acidosis improved earlier when somatostatin analogs were added to insulin therapy. The two presented case subjects reported no benefit, although they had appropriate insulin and fluid therapy. Their biochemical and neurological improvements were delayed, and cerebral edema, hypoglycemia, hypopotassemia, CNS, or any other infections were excluded.

We added somatostatin therapy to inhibit ketogenesis and decrease glucagon secretion. After somatostatin infusion, hyperglycemia improved in both patients, and they were clinically well. Blood glucose levels declined in both patients, and they regained consciousness. Acidosis was also improved a short time after somatostatin therapy.

In conclusion, for patients who do not respond well to standard DKA treatment, somatostatin may be added to the therapy. Counterregulatory hormones may be as effective as insulin in the treatment of DKA. More data and further randomized controlled studies are necessary to expand our findings.

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Address correspondence to Mehmet Bosnak, MD, Department of Pediatrics, Dicle University School of Medicine, Diyarbakir, Turkey. E-mail: