Everolimus resolving hypoglycemia, producing hyperglycemia, and necessitating insulin use in a patient with diabetes and nonresectable malignant insulinoma.

OBJECTIVE: To present a case of management of refractory hypoglycemia due to malignant insulinoma with use of everolimus, resulting in recurrent insulin-requiring diabetes. METHODS: This report describes a case of a nonresectable malignant insulinoma in a 78-year-old patient with long-standing type 2 diabetes mellitus. Endogenous hyperinsulinism was confirmed by a fasting test, which revealed a glucose level of 35 mg/dL and an insulin value of 23.7 µIU/mL. Endoscopic ultrasonography, magnetic resonance imaging, and computed tomography identified a pancreatic mass, infiltration of the superior mesenteric vein, and metastatic lesions in the liver. RESULTS: After chemoembolization of the metastatic lesions, hypoglycemia recurred, despite combined treatment with somatostatin analogues, dexamethasone, and diazoxide. Everolimus, an orally administered mammalian target of rapamycin, was used at a daily dose of 5 mg. After 6 months, the hypoglycemia was controlled, and the patient presented with a C-peptide level of 0.2 ng/mL and secondary hyperglycemia that necessitated insulin treatment. CONCLUSION: The orally administered drug everolimus controlled hypoglycemia due to a malignant insulinoma in a patient with prior insulin-requiring diabetes. Secondary hyperglycemia was an acceptable drug effect (to the patient and managing physicians), in light of the complex and often poorly tolerated treatments available for this rare condition.

Pauta óptima de administración de insulina detemir en sujetos diabéticos tipo 1 con mal control metabólico / Optimal timing of insulin detemir injection in patients with type 1 diabetes and poor metabolic control

Objetivo El objetivo de este estudio fue comparar diversos regímenes de administración de la insulina detemir (IDet) en pacientes con diabetes tipo I y mal control metabólico.Material y métodosEstudio abierto aleatorizado de 24 semanas de duración. Se incluyeron 39 pacientes con diabetes mellitus (DM) tipo I aleatorizados a una inyección de IDet antes de la comida (14,24±00,36[±SD]h) o IDet antes de acostarse (23,19±0,42h). Si no se alcanzaban los objetivos de glucemia, se cambió a la pauta con 2 inyecciones (IDet-12h). En las comidas se administró insulina aspart.ResultadosEn la semana 24 solamente un 12,2% de los pacientes permanecían en el grupo IDet antes de acostarse y un 30,3% en el grupo IDet antes de la comida. El 57,5% restantes pasaron al grupo de IDet-12h. No hubo diferencias entre el grupo de IDet antes de la comida e IDet antes de acostarse. Un subanálisis incluyendo los 3 grupos demostró un mejor control metabólico en el grupo IDet antes de la comida (hemoglobina glicosilada (HbA1c) 7,1±0,2 vs. 7,6±0,4 y 8,1±0,2%, en IDet antes de la comida, IDet antes de acostarse e IDet-12h, respectivamente; p<0,05). El valor de HbA1c inferior a 7%, fue alcanzado en un 30,3% de los pacientes, un 15,2% en el grupo IDet antes de la comida, un 3,3% en el grupo IDet antes de acostarse y 11,5% en grupo IDet-12h. No se encontraron diferencias entre los grupos del tratamiento respecto a la calidad de vida.ConclusiónUna inyección de IDet administrada antes de la comida podría mejorar el control metabólico. Sin embargo, la mayoría de pacientes requiere 2 inyecciones de IDet (AU)

Aim To compare different administration times of insulin detemir (IDet) in patients with type 1 diabetes and poor metabolic control.Material and MethodsThis 24-week open study included 39 people with type 1 diabetes mellitus (DM) randomized to one injection of IDet before lunch (mean 14.24±00.36 (±SD) h) or at bedtime (23.19±0.42h). Whenever target glycemia levels were not reached, the regimen was switched to insulin therapy with two injections (IDet-12h). Insulin aspart was used before main meals.ResultsAt week 24, only 12.2% of patients remained in the IDet bedtime group and 30.3% in the IDet before lunch group. The remaining 57.5% joined the IDet-12h group. There were no differences between the IDet before lunch and IDet bedtime groups. A subanalysis including the three groups demonstrated better metabolic control in the IDet before lunch group (glycosylated hemoglobin (HbA1c) 7.1±0.2 vs. 7.6±0.4 and 8.1±0.2% in IDet before-lunch, IDet bedtime and IDet-12h, respectively; p<0.05). An HbA1c value below 7% was achieved in 30.3% of the patients: 15.2% in the IDet before-lunch group, 3.3% in the IDet bedtime group and 12.2% in IDet-12h group. Quality of life did not differ among treatment groups.ConclusionsOne injection of IDet administered before lunch could improve metabolic control. However, most patients required two injections of IDet(AU)

[Optimal timing of insulin detemir injection in patients with type 1 diabetes and poor metabolic control]. / Pauta óptima de administración de insulina detemir en sujetos diabéticos tipo 1 con mal control metabólico.

AIM: To compare different administration times of insulin detemir (IDet) in patients with type 1 diabetes and poor metabolic control. MATERIAL AND METHODS: This 24-week open study included 39 people with type 1 diabetes mellitus (DM) randomized to one injection of IDet before lunch (mean 14.24 + or - 00.36 (+ or - SD) h) or at bedtime (23.19 + or - 0.42 h). Whenever target glycemia levels were not reached, the regimen was switched to insulin therapy with two injections (IDet-12h). Insulin aspart was used before main meals. RESULTS: At week 24, only 12.2% of patients remained in the IDet bedtime group and 30.3% in the IDet before lunch group. The remaining 57.5% joined the IDet-12h group. There were no differences between the IDet before lunch and IDet bedtime groups. A subanalysis including the three groups demonstrated better metabolic control in the IDet before lunch group (glycosylated hemoglobin (HbA1c) 7.1 + or - 0.2 vs. 7.6 + or - 0.4 and 8.1 + or - 0.2% in IDet before-lunch, IDet bedtime and IDet-12h, respectively; p<0.05). An HbA1c value below 7% was achieved in 30.3% of the patients: 15.2% in the IDet before-lunch group, 3.3% in the IDet bedtime group and 12.2% in IDet-12h group. Quality of life did not differ among treatment groups. CONCLUSIONS: One injection of IDet administered before lunch could improve metabolic control. However, most patients required two injections of IDet.

Hemoglobin Glycosylation Index is not related with blood glucose.

OBJECTIVE: Accurate assessment of blood glucose control is essential to prevent chronic complications in diabetes. Hemoglobin Glycosylation Index (HGI) quantifies the degree to which individuals demonstrate a HbA(1C) higher or lower than average for the population. This study has aimed to assess the relationship between HGI and blood glucose. METHODS: 25 type 1 diabetes subjects (12 men and 13 women), 22.0+/-5.2 (17-34) years old, were instructed to self-monitor glucose with the One Touch Profile capillary glucose meter. HbA(1C) was determined and self-monitored blood glucose levels were studied every 3 months. Diabetic patients were monitored for 3-9 months and 62 measurements of HbA(1C) were included. HbA(1C) was measured by HPLC. Mean blood glucose (MBG) was calculated from self-monitored blood glucose records. A linear regression was calculated between HbA(1C) and MBG during the 60 days before sampling to determine HbA(1C). For each diabetic patient's MBG, a predicted HbA(1C) was calculated from the population regression equation. HGI was then calculated as HGI=observed HbA(1C)-predicted HbA(1C). Blood glucose was analyzed within target range (WTR), below target range (BTR) and above target range (ATR) according to The European Diabetes Policy Group Consensus for type 1 diabetes. RESULTS: A good linear regression between HbA(1C) and MBG was observed (r=.71, r(2)=.497, P=.000). No correlation was found between HGI and the percentage of WTR, BTR or ATR values. Moreover, the percentage of self-monitored blood glucose ATR and BTR was the same for high glycosylators (HGI<0 and ATR: 56.2+/-20.9%; HGI<0 and BTR: 34.5+/-17.5%) as for low glycosylators (HGI>0 and ATR: 52.8+/-25.5%; HGI>0 and BTR: 25.1+/-15.0%). CONCLUSIONS: HGI is determined for both physiological factors and blood glucose. A prospective study is necessary to assess whether HGI, together with HbA(1C), can predict the incidence and severity of chronic complications in diabetic patients.

Insulin-Induced Normoglycemia Reduces Islet Number Needed to Achieve Normoglycemia after Allogeneic Islet Transplantation in Diabetic Mice.

The Edmonton protocol established that insulin independence could be reached with the transplantation of an appropriate number of islet cells. However, to effect a cure, islets from two or three pancreases are needed. The aim of this study was to examine whether normoglycemia, with insulin treatment before and after transplantation, reduces the islet number needed to achieve normoglycemia in allogeneic islet transplantation. Swiss mice were used as donors and recipients. Diabetes was induced by IP administration of streptozotocin (180 mg/kg BW). Diabetic mice were transplanted with 300 (n = 16), 400 (n = 16), or 500 (n = 16) islets under the left kidney capsule. For every group, half the animals were kept normoglycemic with insulin treatment from day 4 before transplantation to day 10 after transplantation. At the end of the study, all normoglycemic mice were given an IP glucose tolerance test (IPGTT). For statistical analysis, paired or unpaired Student's t-test or ANOVA was used. Only insulin-treated mice achieved normoglycemia by the end of the study (37.5% of animals transplanted with 400 islets and 50% transplanted with 300 or 500 islets). At the end of the study, normoglycemic mice transplanted with 300 allogeneic islets showed better glycosylated hemoglobin (HbA1C) than did normoglycemic mice transplanted with 500 islets (300 islets: 2.7 ± 0.2%; 500 islets: 3.6 ± 0.2%; p < 0.05). After the IPGTT, insulin-treated mice transplanted with 500 islets showed abnormal glucose tolerance; however, insulin-treated mice transplanted with 300 or 400 islets showed normal glucose tolerance. Insulin treatment reduced the islet number needed to achieve normoglycemia in allogeneic islet transplantation. The HbA1C and IPGTT results suggest that transplanting smaller numbers of allogeneic islets improves ß-cell function; some studies suggest that this may be due to lower immunogenicity, hypoxia, and inflammation.

Insulin-induced normoglycemia reduces islet number needed to achieve normoglycemia after allogeneic islet transplantation in diabetic mice.

The Edmonton protocol established that insulin independence could be reached with the transplantation of an appropriate number of islet cells. However, to effect a cure, islets from two or three pancreases are needed. The aim of this study was to examine whether normoglycemia, with insulin treatment before and after transplantation, reduces the islet number needed to achieve normoglycemia in allogeneic islet transplantation. Swiss mice were used as donors and recipients. Diabetes was induced by i.p. administration of streptozotocin (180 mg/kg BW). Diabetic mice were transplanted with 300 (n = 16), 400 (n = 16), or 500 (n = 16) islets under the left kidney capsule. For every group, half the animals were kept normoglycemic with insulin treatment from day 4 before transplantation to day 10 after transplantation. At the end of the study, all normoglycemic mice were given an i.p. glucose tolerance test (IPGTT). For statistical analysis, paired or unpaired Student's t-test or ANOVA was used. Only insulin-treated mice achieved normoglycemia by the end of the study (37.5% of animals transplanted with 400 islets and 50% transplanted with 300 or 500 islets). At the end of the study, normoglycemic mice transplanted with 300 allogeneic islets showed better glycosylated hemoglobin (HbA1C) than did normoglycemic mice transplanted with 500 islets (300 islets: 2.7 +/- 0.2%; 500 islets: 3.6 +/- 0.2%; p < 0.05). After the IPGTT, insulin-treated mice transplanted with 500 islets showed abnormal glucose tolerance; however, insulin-treated mice transplanted with 300 or 400 islets showed normal glucose tolerance. Insulin treatment reduced the islet number needed to achieve normoglycemia in allogeneic islet transplantation. The HbA1C and IPGTT results suggest that transplanting smaller numbers of allogeneic islets improves beta-cell function; some studies suggest that this may be due to lower immunogenicity, hypoxia, and inflammation.