Large Doses Of Insulin Research Articles

Using insulin pump for glycemic control in patients with severe insulin resistance

BackgroundPatients with type 2 diabetes using a continuous subcutaneous insulin infusion (CSII) often require large doses of insulin and need to change their insulin administration sets frequently. A proposed solution to this problem is to use concentrated insulin in their insulin pump; however, insulin pumps are programmed to administer U-100 insulin. Therefore, these patients are at greater risk of hypoglycemia and are responsible for adjusting daily doses. Case summaryThe solution for our patient encountering this problem was to administer half of his daily basal insulin via subcutaneous injection and allow the CSII to administer the remainder through automated insulin delivery (AID). When this strategy was initiated, the patient’s A1C was > 14%. After 5 months of follow-up, the patient’s A1C was 8.3% and he reported improved quality of life. Practice implicationsThis technique allows patients with high insulin requirements to benefit from AID without the safety risks associated with using concentrated insulin.

Prescribing patterns of adjunctive therapy for the treatment of type 1 diabetes mellitus among Australian endocrinologists.

Many people living with type 1 diabetes (type 1 diabetes mellitus (T1DM)) do not meet glycaemic targets. Adjunctive therapies have both risks and metabolic benefits and may have a role in selected patients. To review the prescribing patterns of adjunctive therapy for the treatment of T1DM diabetes in Australia. We conducted an online survey of Australian endocrinologists and endocrinology registrars. We surveyed the frequency of, motivations and concerns regarding the prescription of metformin, dipeptidyl peptidase-4 (DPP-IV) inhibitors, sodium-glucose transport protein 2 (SGLT-2) inhibitors and glucagon-like peptide 1 receptor agonist (GLP1RA) in T1DM. Fifty-two practitioners participated. Most respondents (94%) had prescribed adjuncts for the treatment of T1DM in some form. Weight (89%), large insulin doses (73%), glycaemic variability (52%), high HbA1c (48%) and the presence of cardiovascular disease (48%) were the most common factors determining the use of adjuncts. The most commonly prescribed adjuncts were metformin (94%) and SGLT-2 inhibitors (65%). Respondents who had never prescribed an SGLT-2 inhibitor (n = 18) reported risk of diabetic ketoacidosis (DKA) (100%), off-label status (39%), lack of evidence (39%), withdrawal of support from the European Medicines Agency (17%) and cost (17%) as factors contributing to their decision. Thirty-one respondents (60%) had prescribed a GLP1RA. Among those who had never prescribed a GLP1RA (n = 21), off-label status (57%), lack of evidence (48%), cost (38%) and expected lack of efficacy (14%) were factors affecting their decision. Only five respondents (10%) had prescribed a DPP-IV inhibitor. Australian endocrinologists commonly prescribe adjuncts to address cardiometabolic concerns in T1DM. DKA risk and off-label status are significant factors contributing to reluctance to prescribe.

1261-P: Prevalence of Nonalcoholic Fatty Liver Disease and Liver Fibrosis in Patients with Type 1 Diabetes

Nonalcoholic fatty liver disease (NAFLD) is a common comorbid condition in patients with type 2 diabetes. However, little is known about its prevalence among patients with type 1 diabetes (T1D). We used transient elastography to measure controlled attenuation parameter (CAP) as steatosis indicator and liver stiffness measurement (LSM) as fibrosis indicator. We evaluated 537 patients with T1D: age 49±16 years; 55% females; 81% non-Hispanic whites; BMI 27.6±5.5 kg/m2; diabetes duration 29±15.6 years; A1C 7.1±1.0%; total daily insulin (TDI) 49±28 U/day; ALT 19±10 IU/L; AST 22±8 IU/L. The prevalence of NAFLD (CAP≥274 dB/m) was 28.5% (95% CI 24.6-32.6) and fibrosis (LSM≥7 kPa) 8.4% (95% CI 6-11). Moreover, 4.1% (95%CI 2.6-6.2) of NAFLD had ≥F2 fibrosis (LSM ≥ 8.2 kPa) suggesting nonalcoholic steatohepatitis (NASH). Higher CAP positively correlated with higher BMI (p<0.001); diabetes duration (p<0.01); and TDI (p<0.001). It was common in males (OR 2.1, 95%CI 1.3-3.5, p<0.01). Among those with NAFLD, mean ALT was 21±11 IU/L (p=0.02), AST 22±7 IU/L, BMI 32.7±5.8 kg/m2, and waist circumference (WC) 103±15 cm. Among those with fibrosis, mean ALT was 23±10 IU/L (p=0.01), AST 24±7 IU/L (p=0.03), BMI 31.7±6.4 kg/m2 and WC 104±15 cm. Obesity (BMI >30 kg/m2) and larger WC (>102 cm in men, >88 cm in women) were associated with increased risk for hepatic steatosis (OR 3.1, 95% CI 1.6-6.0, p=0.001; OR 4.0, 95% CI 2.2-7.5, p<0.001, respectively). In conclusion, prevalence of NAFLD and liver fibrosis is considerable among patients with T1D, while liver enzymes are within normal range. Obesity and large waist circumference are associated with increased risk of hepatic steatosis. Independent predictors of NAFLD include: higher BMI, longer diabetes duration, higher TDI and male gender. Screening for NAFLD and liver fibrosis is advisable for patients with T1D irrespective of their liver enzymes, particularly in patients with higher BMI, longer diabetes duration or among those treated with larger insulin dose. Disclosure T.Salah: None. R.Mccarragher: None. L.Demattos: None. M.Tran: None. O.Hamdy: Advisory Panel; Abbott Nutrition, Nemaura Medical, L-Nutra Inc., Twin Health, Consultant; Sanofi, Research Support; Novo Nordisk, Eli Lilly and Company, Gilead Sciences, Inc., Stock/Shareholder; Healthimation. S.Tomah: Employee; Altimmune. M.Al-badri: None. K.Kibaa: None. S.E.Dhaver: None. M.P.Curry: Advisory Panel; Mallinckrodt PLC, Alexion Pharmaceuticals, Inc., Albireo. M.Lai: None. Z.Jiang: Advisory Panel; Olix Pharmaceutical, Research Support; Pfizer Inc., Gilead Sciences, Inc. A.Khater: None.

PSUN140 “Awakening of the Beta Cell©”

Abstract Background Endocrinologists often manipulate hormones by adding medication or replacing hormones that are no longer being produced. However, replacing hormones artificially causes hormone producing cells that are still viable to become suppressed and ultimately shut down. For example, with estrogen, testosterone, or cortisol replacements, the cells responsible for the production become inactive. This study tries to show that the same process affects the beta cells in the pancreas. The more insulin given, the further these beta cells become suppressed, and block natural insulin production. Rather than insulin resistance, our results showed that high dose artificial insulin inhibits the beta cells and prevents natural production. Methods To perform this study, we took a random sample of 13 type 2 diabetics on high doses of insulin. Prior to the study, they were taking over 20 units of bolus prandial insulin 3x daily, and over 50 units of basal insulin 1-2x daily. We reduced their insulin by half, monitored them closely, instructed them to change their lifestyle and follow a proper diabetic diet. Results Out of the 13 patients, 10 of them showed significant improvement on follow-up evaluation. The HbA1c and finger sticks had remained consistent or improved with the reduced dose. This showed the beta cells had been suppressed and were now becoming more responsive. Overall, the patients responded well to the reduction in their high doses of insulin, and it appeared that the pancreas’ beta cells began to naturally produce insulin. Conclusion The results showed that a lifestyle change along with the reduction in insulin was successful in treating patients with Type 2 Diabetes. Like any other hormone, prescribing large doses of insulin has been indirectly suppressing the action of beta cells. This suggests that patients may not be developing insulin resistance, rather their beta cells are losing their functionality. To control their Type 2 diabetes, patients should focus on pursuing a healthy lifestyle and lowering their insulin. Limitations to the study were that the threshold where the beta cells no longer function has not yet been quantified, and patient non-compliance with monitoring and lifestyle changes, resulting in the need for increased insulin. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Rescue effects of insulin on the cytotoxic effects of bitter melon extract in the human breast cancer cells

Bitter melon extract (BME) is known to inhibit breast cancer cells proliferation. Due to the high metabolic rate of cancer cells, we hypothesized that low glucose levels are detrimental to cell survivability and that BME exerts a cytotoxic effect by altering the ability of a cell to utilize glucose. Through this study, we seek to investigate if insulin is capable of mitigating the cytotoxic effects of BME and provide a “rescue effect”.Fresh bitter melons were purchased from an Asian grocery store and the extract (BME) was prepared, centrifuged, and filter sterilized. The MCF‐7 cells were cultured in the DMEM medium (normal or low glucose) with either 1% or 2 % BME (v/v) and in the presence or absence of insulin at various doses [50ng/mL, 100ng/mL, 200ng/mL]. After culturing cells for 24 hours in standard DMEM complete medium, BME and insulin were added to corresponding wells and pictures of cultures were taken every 24 hours for 2 days. After the 2 days, cell viability was then assessed using an MTT colorimetric assay at 620 nm.BME dose‐dependently inhibited MCF‐7 cell viability. Insulin demonstrated a rescue effect and increased the cell viability despite the addition of BME. Insulin also dose‐dependently enhanced MCF‐7 cell viability to an extent when added alone. Following were the % absorbance values with increasing doses of insulin. All values are relative to control (without any addition of BME or Insulin) considered as 100% and corrected for absorbance of DMEM alone; [DMEM only – 38.33%, 1% BME – 34.33%, 0% BME + 200ng Insulin – 49.87%, 1% BME + 50ng Insulin – 39.53%, 1% BME + 100ng Insulin – 39.97%, 1% BME + 200ng Insulin – 41.70%]. The 1% BME (bitter melon extract) is the positive control in our studies as our lab have found BME to be toxic to MCF‐7 cells. The same trial was repeated with 2% BME in order to better visualize the cytotoxic effects of BME and further demonstrate the subsequent rebound in cell viability following addition of insulin. All values are relative to control (without any addition of BME or Insulin) considered as 100% and corrected for absorbance of DMEM alone; [DMEM only – 58.87%, 2% BME – 17.07%, 0% BME + 200ng Insulin – 63.97%, 2% BME + 50ng Insulin – 55.70%, 2% BME + 100ng Insulin – 55.43%, 2% BME + 200ng Insulin – 59.30%].When we treated cells with increasing doses of insulin, an enhanced rescue effect was seen as reflected by the increasing absorbance values. We further tested the effects of BME and insulin by culturing the cells in low glucose DMEM. The raw data is included in the abstract due to space limitation.Our data indicates the addition of insulin is capable of rescuing cells from the cytotoxic effects of BME. Insulin seems to be capable of mitigating the cytotoxic effects of BME and, in some cases, even enhancing the viability of cells despite the prior treatment with BME. The relatively diminished rescue effect with 200ng of insulin and 2% BME may be due to the inherent strain the cells were already experiencing with BME. The high dose of insulin, coupled with the strain of attempting to replicate in sub‐optimal conditions, may have led to cells that were incapable of meeting the metabolic demand placed by the large dose of insulin and subsequent influx of glucose. Further study may be warranted to discover the threshold of benefit that insulin can provide and amount of glucose necessary for, or detrimental to, cell survival.

The role of sodium-glucose cotransporter 2 inhibitors in the treatment of type 2 diabetes: from clinical research to real practice

In type 2 diabetes mellitus (T2DM), the development and progression of cardiovascular diseases occurs, which allows it to be considered as a cardiorenal metabolic syndrome. This should be taken into account when choosing hypoglycemic drugs. Patients with T2DM receiving insulin therapy often have a long history of diabetes, cardiovascular disease, chronic kidney disease, obesity, and need to be prescribed high doses of insulin and/or complex insulin therapy regimens to maintain glycemic control, which does not always lead to the achievement of target levels of glycemia and glycated hemoglobin (HbA1c). Adding to any insulin therapy regimen drugs from the class of sodium-glucose cotransporter type 2 inhibitors (SGLT-2), which have proven their cardio- and renoprotective properties, seems to be a rational combination in patients with T2DM and may have a number of advantages. The article presents 4 clinical examples of dapagliflozin administration, a drug from the SGLT2 class, to patients who are on insulin therapy, having T2DM with a long history (10–26 years), as well as cardiovascular diseases, chronic kidney disease, and obesity. Dapagliflozin administration allowed to improve glycemic control, to stabilize the insulin dose, as well as reduce body weight without increasing the frequency of serious episodes of hypoglycemia in patients who initially received large doses of insulin. In the long term, we can expect reduction of the progression of cardiovascular risks and the risks of hospitalization due to existing complications of the disease.

2195-PUB: Use of U500 Insulin in External Pump for Insulin-Resistant Diabetic Patients: A French Experience

Use of large insulin doses is more frequent in diabetes due to an increase in the prevalence of severe obesity worlwide. Insulin-associated treatments such as metformin or GLP-1 receptor agonists (GLP-1RA) can help and use of insulin concentrated at 500 IU/ml (U500) has been associated with an improve in glycemic control in previous studies including severe insulin resistant patients. We report our experience of U500 in subjects with high HbA1c despite insulin pump therapy (CSII) combined or not with metformin and/or GLP-1RA. Eighteen T2D and 3 T1D were studied (13M and 8F), age: 59.5 ± 9.6 years, diabetes duration : 18.8 ± 9.8 years. Eight subjects used metformin and 7 used GLP-1RA (5 used metformin and GLP-1RA). Treatment with U500 was carried out during a 5-day hospitalization. Metformin and/or GLP-1RA were continued or not during the follow-up according to the decision of the patient’s diabetologist. Mean duration of follow-up was 9 months. A decrease in HbA1c was found (initial vs. final) : 9.4 ± 1.2% vs. 8.5 ± 1.3% (p =0.05). No change was found for weight : 123.9 ± 26.4 kg vs. 121.0 ± 30.3 kg (NS), BMI : 41.5 ± 7.2 kg/m2 vs. 40.2 ± 7.3kg/m2 (NS), daily total insulin needs (U100 equivalent) : 198.4 ± 70.5 IU vs. 228 ± 121 IU (NS), basal needs : 81.8 ± 29.2 IU vs. 87 ± 36 IU (NS) and prandial needs : 116.5 ± 61.3 IU vs. 143 ± 110 IU (NS). No changes were found for lipidic parameters as total cholesterol (TC) : 1.85 ± 1.10 g/l vs. 1.80 ± 0.92 g/l (NS), HDL-C : 0.36 ± 0.08 g/l vs. 0.31 ± 0.06 g/l (NS), LDL-C : 0.83 ± 0.32 g/l vs. 0.71 ± 0.30 g/l (NS) and TG : 3.98 ± 7.56 g/l vs. 3.4 ± 5.3 g/l (NS). No change in use of metformine and/or GLP-1RA and no side effect were found during the follow-up. Conclusion: In our practice, use of U500 in insulin-resistant patients treated with CSII is well tolerated and is associated with a decrease in HbA1c despite no change in weight or daily insulin needs. Evolution of glycemic variability (including TIR and hypoglycemias) using continuous glucose monitoring is currently being analyzed. Disclosure Y. Oualit: None. D. Pâris: Board Member; Self; Novo Nordisk Inc. Consultant; Self; Eli Lilly and Company, Sanofi-Aventis. L. Kessler: Consultant; Self; Lilly Diabetes, Medtronic, Novartis Pharma K.K., Novo Nordisk A/S, Vertex Pharmaceuticals. T. Bahougne: None. N. Jeandidier: Consultant; Self; Sanofi-Aventis. Research Support; Self; Lilly Diabetes. L. Meyer: Board Member; Self; Abbott, Lilly Diabetes, Novo Nordisk A/S.

A case of type B insulin resistance presenting at a district general hospital

Abstract Type B insulin resistance is a rare autoimmune condition with just over 100 cases described in the literature. We describe here the case of a young female who presented to our district general hospital with a rapid onset of profound insulin resistance not ameliorated by intensive insulin therapy.A previously fit and well 30‐year‐old woman was referred to hospital for hyperglycaemia without ketosis and clinical features consistent with diabetes. She had a normal BMI and no family history of note. Initially, treatment with oral medication was prescribed but due to a worsening of hyperglycaemia and HbA1c over the next few days, insulin therapy was introduced. It was quickly recognised that large doses of insulin given via subcutaneous and intravenous routes had little effect on her blood glucose with levels remaining well above 20mmol/L at maximum therapy.The presence of acanthosis nigricans along with cutaneous stigmata of connective tissue disease was noted and the case was referred to a specialist centre for further testing due to apparent severe insulin resistance. Antibody testing and further investigations were conducted revealing a final diagnosis of type B insulin resistance with an associated new diagnosis of systemic lupus erythematosus.Treatment of this patient's diabetes with immunosuppressive medication has been commenced with the hope of inducing remission. Copyright © 2020 John Wiley & Sons.

Incidence of severe hypoglycemia and its association with serum adiponectin in Japanese patients with type1 and insulin-treated type2 diabetes: The Fukuoka Diabetes Registry.

Aims/IntroductionThe incidence of severe hypoglycemia and its risk factors including an insulin‐sensitizing adipokine, adiponectin, were prospectively investigated in Japanese patients with type 1 or insulin‐treated type 2 diabetes.Materials and MethodsA total of 207 participants with type 1 diabetes (mean age 55 years) and 1,396 with insulin‐treated type 2 diabetes (mean age 65 years) from the local diabetes registry were followed for 5 years (follow‐up rate 99%). Severe hypoglycemia was defined as events requiring the assistance of others for recovery from hypoglycemia.ResultsThe incidence of severe hypoglycemia was 9.2 per 100 person‐years in those with type 1 diabetes, and 2.3 per 100 person‐years in those with insulin‐treated type 2 diabetes, respectively. For type 1 diabetes, the risk was significant in those with a history of severe hypoglycemia within the previous year, slow eating and higher serum adiponectin (the highest vs the lowest in quartile hazard ratio 2.36, 95% confidence interval 1.22–4.69). For insulin‐treated type 2 diabetes, the risk included age ≥65 years, history of severe hypoglycemia within the previous year, alcohol consumption ≥60 g/day, larger insulin dose and higher serum adiponectin (the highest vs the lowest in quartile, hazard ratio 2.95, 95% confidence interval 1.22–4.69). For all participants, the incidence of severe hypoglycemia increased along with serum adiponectin (age‐ and sex‐adjusted hazard ratio 1.65 per 1 standard deviation increase of log serum adiponectin, 95% confidence interval 1.45–1.87).ConclusionsThe incidence of severe hypoglycemia was prospectively determined, and the association between severe hypoglycemia and higher serum adiponectin was observed in Japanese patients with type 1 and insulin‐treated type 2 diabetes.

Rabson Mendenhall Syndrome; a Case Report and Review of Literature

Genetic disease is caused by a gene change. Genetic disease is one of the types of diseases affecting the personal, family and social life. One of the types of genetic disease is Rabson Mendenhall Syndrome. The Rabson Mendenhall Syndrome (RMS) was first described by Rabson and Menden-hall in 1956. Rabson Mendenhall syndrome is an extremely rare genetic disorder with autosomal recessive inheritance of unknown prevalence that is estimated to affect less than 1 per million people worldwide characterized by severe insulin resistance. The present study is a case report of a patient with Rabson Mendenhall Syndrome in Iran. A 6 year old girl presented with severe hyperglycemia and loss of consciousness and acidosis. In spite of taking large doses of insulin, her sugars were uncontrolled. She had severe acanthosis nigricans. There was associated growth retardation, dental dysplasia, distent abdomen, emaciated extremities and clitoromegaly. In last admission with diabetic ketoacidosis she was treated with intravenous fluids, insulin drip, metformin and also pioglitazone, antibiotics and other supportive treatments as needed, but unfortunately after few days this treatments could not save her and patient expired. There is no complete cure for the condition and the current treatments are difficult and not very promising.

SUN-164 Use of Metformin, Premixed Insulin, and Glucagon-Like Peptide-1 Receptor Agonist as a Therapeutic Approach for Uncontrolled Type 2 Diabetes Mellitus

Background: Large doses of basal insulin may do little to improve glycemic. Adding pre-prandial insulin increases the number of injections and complicates treatment. Simplifying medication regimen by decreasing injections may improve compliance and lead to improved Hemoglobin A1c (HbA1c). Traditionally once prandial insulin is added, oral medications and other injectable insulin sparing agents are stopped except metformin. There are no published studies on use of Glucagon-like peptide-1 receptor agonists (GLP-1 RA) with prandial insulin or premixed insulin. The purpose of this retrospective review was to assess if changing patients with long history of poorly controlled diabetes on large doses of basal insulin with or without pre-prandial insulin to premixed insulin, GLP-1 RA and metformin improved glycemic control over 12 months. Methods: We conducted a retrospective cohort study of adult patients with Type 2 Diabetes (T2DM) who presented to our outpatient medical center between January 1, 2000 and November 1, 2017. We selected all patients who were given premixed insulin and a form of GLP-1 RA simultaneously with or without metformin with no other diabetic medication and had at least a 3 month follow-up HbA1c. We reviewed HbA1c, weight and cumulative daily insulin dose over 12 months. We collected all demographic data as well as adverse events. Results: 32 patients met inclusion criteria with 31 of the 32 patients having 12 month HbA1c data. Average duration of T2DM was 14.2 (SD 7.1) years. Mean HbA1c at baseline was 10.5% (SD 2.1). By 6 months mean HbA1c had declined to 8.6% (SD 2.1). At 12 months mean HbA1c change was -2.3 (SD 2.38, [95% CI: -3.183 to -1.437]; p = < 0.0001). At 12 months cumulative insulin dose was -34.9 units less than total initial insulin (SD 58.9 [95% CI: -56.55 to -13.32]; P = 0.0025). Average weight loss was -3.3 LBS (SD 20.1 [95% CI: -10.73 to 4.151]; p= 0.373). After 12 months 23% (7/31) of patients had HbA1c ≤ 7% and 61% (19/31) had HbA1c ≤ 8%. Of note 5 additional patients stopped regimen after <3 months, 3 for nausea, 1 for pancreatitis and 1 for skin reaction. Conclusion: Despite cumulative daily dose of insulin decreasing, using metformin, premixed insulin and GLP-1 RA in a historically difficult to control population with T2DM, improved glycemic over duration of 12 months. Prospective randomized studies need to be done to assess the benefit of this unique combination of available medication therapy.

Hypoglycemia secondary to factitious hyperinsulinism in a foster care adolescent - a case report of munchausen syndrome in a community hospital emergency department setting

BackgroundFactitious disorder causing hypoglycemia is a psychiatric condition in which patients deliberately use blood sugar lowering medications to cause severe symptoms for the purposes of hospitalization or other primary gains.Case presentationWe report a case of factitious hypoglycemia in a 19-year-old foster care adolescent female who presented to the Emergency Department with recurrent hypoglycemic episodes, to the degree that the patient required large amounts of dextrose and further management by intensive care unit hospitalization. Further inquiry revealed that the patient intentionally injected herself with large doses of insulin for the purposes of seeking hospital admission.ConclusionFactitious disorder in the setting of recurrent hypoglycemia episodes may warrant a psychiatric referral and appropriate discharge follow-up to avoid multiple hospitalizations. Presentation in a non-diabetic patient from insulin use is a type of illness that is a challenge for emergency department physicians to appropriately diagnose and treat. Classic findings include a low blood sugar level, suppressed C-peptide level, and an inappropriately elevated insulin level. Recognizing these psychiatric presentations is crucial in order to stabilize patients and prevent unnecessary testing.

Insulin Pump in Difficult to Control Type 2 Diabetes: A Single Center, Five Years' Experience.

ObjectiveDue to a progressive decline in beta-cell function, a considerable number of patients with type 2 diabetes mellitus (T2D) ultimately require multiple daily injections of large doses of insulin for glycemic control. Majority of studies have reported only short-term benefits of continuous subcutaneous insulin infusion (CSII) using an insulin pump in T2D. Our five-year follow-up data of CSII in T2D is one of the few studies showing persistent benefit in glucose control in this population.Research design and methodsWe did a chart review of patients treated with an insulin pump for five years. Inclusion criteria were: type 2 diabetes, 18–75 years of age, glycosylated hemoglobin (HbA1c) more than 6.5% (48 mmol/mol) on multiple doses of insulin (MDI > four injections per day) or more than 100 units of insulin/day, wide glycemic excursions, and intractable hypoglycemia. We identified a total of 13 patients. The primary endpoint was change in HbA1c from baseline to five years. We also reviewed the difference in weight, basal insulin requirements, hypoglycemia, and patient satisfaction questionnaire at one year. Exclusion criteria were: type 1 diabetes (T1D) and pregnancy.ResultsThe HbA1c at five years was found to be 7.72% (61 mmol/mol) compared to a baseline of 8.89% (74 mmol/mol), p-value 0.0076. We did not find any increased risk of severe hypoglycemia, weight gain, and insulin requirement.ConclusionsThe beneficial effect of insulin pump persisted for five years of follow-up, suggesting it as a valuable treatment option for difficult to treat T2D.

Combination of Premixed Insulin with Glucagon-Like Peptide-1 Receptor Agonist (GLP-1) for Uncontrolled Type 2 Diabetes Mellitus (T2DM) Patients

Background: Despite multiple therapeutic options for people with T2DM, 48% of people do not achieve Hemoglobin A1c (HbA1c) goal. GLP-1 receptor agonists may be beneficial to patients with T2DM who are on large insulin doses and are obese. GLP-1 receptor agonists are often used with oral medications and/or basal insulin. GLP-1 agents are not typically used with those on prandial insulin. Clinical cases: We present 2 cases of uncontrolled T2DM whose HbA1c significantly improved on GLP-1 and daily mixed insulin. Patient A is a 62 y/o M with T2DM for 15 years, weight of 112 kg (BMI 35), HbA1c of 10.2% (diabetes ref range &amp;gt; 6.4%), on 65u insulin detemir BID (total daily insulin 0.9 u/kg). HbA1c decreased to 7.1% by 2 month on dulaglutide 1.5mg weekly, insulin Humalog mix 75/25 45u BID (total daily insulin 0.8u/kg) and metformin ER 1000mg BID. HbA1c at 12 months was 6.1% and weight 112kg (BMI 35). Patient B is a 61 y/o F with T2DM for 17 years, weight of 92 kg (BMI 35), HbA1c of 10.9%, on 50u insulin glargine BID and not adherent to her insulin lispro (total daily insulin 1.6 u/kg). HbA1c decreased to 6.3% at 2 month on dulaglutide 1.5 mg weekly, insulin Novolog mix 70/30 30u BID (total daily insulin 0.7u/kg) and metformin ER 500mg BID. HbA1c at 12 months was 6.6%, and weight decreased to 87kg (BMI 34). Discussion: Our patients were on metformin and high dose insulin without HbA1c improvement. Their regimens were changed to once weekly GLP-1 agonists with mixed insulin which showed improved and sustained glycemic control after one year without major hypoglycemic events. Conclusion: These cases highlight the potential utility of GLP-1 receptor agonist therapy in combination with mixed insulin for patients with uncontrolled T2DM on high dose insulin. We hypothesize that increased compliance may be an import factor but further research needs to be completed. Disclosure S. Fazeli: None. N. Ehrhardt: None.

Postprandial Dosing of Bolus Insulin in Patients with type 1 Diabetes: a Cross-sectional Study Using Data From the T1d Exchange Registry

To assess the prevalence and characteristics of patients with type 1 diabetes (T1D) who dose bolus insulin postprandial (PostP) versus preprandial (PreP). Data for this cross-sectional study were obtained from 21,533 participants in the T1D Exchange Registry. Data were drawn from the enrollment questionnaire. Patients who dosed 'immediately before meal' or 'several minutes before meal' were classified as PreP. Patients who dosed 'during meal' or 'after meal' were classified as PostP. Data reported (PostP vs. PreP) are mean ± SD and percentage, as appropriate. After exclusion of patients who did not answer the dose-timing question or who selected 'not given regularly' or 'depends on glucose level prior to meal,' (4,229 of 25,762), 21,533 patients were included in the study. Ninety-nine percent of patients used rapid-acting insulin analogues; 32% dosed insulin PostP. Compared to PreP, children <18 years of age dosing PostP were characterized by higher glycated hemoglobin (HbA1c) (8.7 ± 1.5% [72 ± 16.4 mmol/mol] vs. 8.4 ± 1.7% [68 ± 18.6 mmol/mol]), larger insulin dose (1.2 ± 0.7 IU/kg/day vs. 1.1 ± 0.7 IU/kg/day), greater prevalence of history of hypoglycemia, and diabetic ketoacidosis. Adults who dosed PostP were characterized by younger age (33.0 ± 15.3 years vs. 39.5 ± 16.6 years), higher HbA1c (8.3 ± 1.5% [67 ± 16.4 mmol/mol] vs. 7.8 ± 1.5% [62 ± 16.4 mmol/mol]), and larger insulin dose (1.0 ± 0.6 IU/kg/day vs. 0.9 ± 0.5 IU/kg/day) than PreP. This study reveals that a large proportion of patients dose bolus insulin PostP. Despite the use of current rapid-acting insulin analogues, patients who dose PostP are characterized by poorer glycemic control in all patients and a greater prevalence of history of severe hypoglycemia and diabetic ketoacidosis in children. BMI = body mass index; CGM = continuous glucose monitoring; DKA = diabetic ketoacidosis; HbA1c = glycated hemoglobin; PostP = postprandial; PreP = preprandial; SMBG = self-monitored blood glucose; T1D = type 1 diabetes.

Development and Implementation of a U-500 Regular Insulin Program in a Federally Qualified Health Center.

According to the 2014 National Diabetes Statistics Report (1), 29.1 million people in the United States (9.3% of the population) have diabetes; 28.7% of adults >18 years of age use insulin alone or in combination with oral medications (1). Nearly 35% of U.S. adults are obese, and this rate has steadily increased during the past 20 years (2). With the growing number of adults with diabetes and increasing rates of obesity, there is an increased prevalence of insulin resistance and thus a need for large daily doses of insulin for glycemic control. U-500 regular (U-500R) insulin has been used for decades but has gained popularity in the past 10 years as a result of the increase in obesity and insulin resistance. The potency of U-500R insulin is five times greater than U-100 insulins; 1 mL of U-500R contains 500 units of insulin compared to 1 mL of standard U-100 insulin, which contains 100 units. The concentrated U-500R is advantageous for patients who are severely insulin resistant, requiring large doses of U-100 insulin because altered insulin absorption and leakage can occur when large volumes are injected, which reduces efficacy (3,4). To enhance U-100 insulin efficacy, practitioners often split the dose when the volume exceeds 40–60 units per dose. However, from the patient perspective, needing two injections to administer a single dose may be undesirable. For this reason, converting a patient requiring high doses of insulin from U-100 to U-500R could be considered because this option would decrease volume by 80% while still delivering the required number of units. The pharmacokinetic characteristics of U-500R appear to fall between those of NPH insulin and U-100 regular insulin and allow U-500R to provide both basal and mealtime insulin coverage (5). Because of its pharmacokinetic properties, delayed peak effect, and prolonged duration of …

Œdème insulinique au cours d’une glycogénose hépatique

IntroductionHepatic glycogenosis is a rare syndrome, which includes poorly controlled diabetes mellitus, hepatomegaly, delayed puberty, and growth delay. Insulin edema is sometimes associated. Case reportAn 18-year-old woman presented with diffuse edema, hepatomegaly, amenorrhea, uncontrolled diabetes, and elevated transaminases and cholestasis. Hepatic ultrasonography and abdominal computed tomographic scan confirmed the hepatomegaly. The liver biopsy showed a massive glycogenosis and the diagnosis of hepatic glycogenosis was confirmed. Too large doses of insulin were responsible of diffuse edema. Diabetes equilibration and diminution of insulin intakes allow correction of this disorder. ConclusionExcess of insulin can lead to excessive hepatic glycogen storage by activation of glycogenosis enzymes. Biological manifestations consist on elevated liver enzymes and hyperlactatemia. There is a link between administration of high dose of insulin and edema. Hepatic glycogenosis should be suspected when diabetes is uncontrolled and be considered as a differential diagnosis of steatosis. It may be associated and revealed by insulin edema directly related to excessive insulin intakes.

Optimal Dose and Method of Administration of Intravenous Insulin in the Management of Emergency Hyperkalemia: A Systematic Review.

Background and ObjectivesHyperkalemia is a common electrolyte disorder that can result in fatal cardiac arrhythmias. Despite the importance of insulin as a lifesaving intervention in the treatment of hyperkalemia in an emergency setting, there is no consensus on the dose or the method (bolus or infusion) of its administration. Our aim was to review data in the literature to determine the optimal dose and route of administration of insulin in the management of emergency hyperkalemia.Design, Setting, Participants, & MeasurementsWe searched several databases from their date of inception through February 2015 for eligible articles published in any language. We included any study that reported on the use of insulin in the management of hyperkalemia.ResultsWe identified eleven studies. In seven studies, 10 units of regular insulin was administered (bolus in five studies, infusion in two studies), in one study 12 units of regular insulin was infused over 30 minutes, and in three studies 20 units of regular insulin was infused over 60 minutes. The majority of included studies were biased. There was no statistically significant difference in mean decrease in serum potassium (K+) concentration at 60 minutes between studies in which insulin was administered as an infusion of 20 units over 60 minutes and studies in which 10 units of insulin was administered as a bolus (0.79±0.25 mmol/L versus 0.78±0.25 mmol/L, P = 0.98) or studies in which 10 units of insulin was administered as an infusion (0.79±0.25 mmol/L versus 0.39±0.09 mmol/L, P = 0.1). Almost one fifth of the study population experienced an episode of hypoglycemia.ConclusionThe limited data available in the literature shows no statistically significant difference between the different regimens of insulin used to acutely lower serum K+ concentration. Accordingly, 10 units of short acting insulin given intravenously may be used in cases of hyperkalemia. Alternatively, 20 units of short acting insulin may be given as a continuous intravenous infusion over 60 minutes in patients with severe hyperkalemia (i.e., serum K+ concentration > 6.5 mmol/L) and those with marked EKG changes related to hyperkalemia (e.g., prolonged PR interval, wide QRS complex) as an alternative to 10 units of short acting insulin. Because the risk of hypoglycemia is increased with using large insulin doses, sufficient glucose (60 grams with the administration of 20 units of insulin and 50 grams with the administration of 10 units) should be given to prevent hypoglycemia, and plasma glucose should be frequently monitored.

Oral insulin (human, murine, or porcine) does not prevent diabetes in the non-obese diabetic mouse

Studies have shown oral insulin prevents type 1 diabetes (T1D) in mouse models, however human trials were inconclusive. We tested the ability of different insulins to prevent T1D in non-obese diabetic mice. Mice received oral insulin or PBS twice weekly and disease was monitored. Contrary to previous studies, no insulin tested showed significant ability to prevent T1D, nor did testing of linked suppression in a delayed type hypersensitivity model have reproducible effect. To investigate delivery of antigen within the GI tract, blue dye was fed to mice. Dye traveled 5–8cm from stomach to small intestine within 10s, suggesting orally administered antigen may not get digested in the stomach in mice. Insulin incubated with jejunum extracts was instantly digested. Thus, in humans large doses of insulin may be required to achieve tolerance as antigen may be more vulnerable to digestion in the stomach even before reaching the small intestine.

Medication safety strategies worth sharing with hospital pharmacists

Improving medication safety is at the forefront of most hospital pharmacists'minds. This complex issue has numerous facets and nuances,and nearly endless opportunities for pharmacists to jump in and makeinterventions that change hospital policy resulting in better, safer care.