Subcutaneous Regular Insulin Research Articles

Prevalence of hypophosphatemia in children with diabetic ketoacidosis and treatment with subcutaneous regular insulin. Observational study

To estimate the incidence of hypophosphatemia in children with DKA, treated with subcutaneous regular insulin (IRS), and to explore factors associated with this complication. Prospective, observational study. Patients diagnosed with DKA hospitalized in the general care ward were included. Data on phosphatemia, glycemia, acid-base status, and IRS amount (U/kg) received were recorded at baseline and after 24 h of treatment. Hypophosphatemia was defined as values below 2.5 mg/dl. The correlation between initial phosphate and at 24 h of treatment was evaluated; the incidence of hypophosphatemia at 24 h was expressed as a percentage of the total number of patients. 30 patients were included, 15 were female, mean age 11.4 ± 3.2 years. At 24 h of treatment with IRS, 36.7% (95%CI 22-55%) presented hypophosphatemia, mean value 1.9 ± 1.5 mg/dl. Initial bicarbonate < 10 mmol/L acted as a predictor of hypophosphatemia (OR 7.5; 95%CI 1.4-39.8%; p = 0.01). No patient required intravenous phosphate correction, and no associated clinical complications were observed. In the group studied, the incidence of hypophosphatemia reached 36.7% at 24 hours of treatment. Initial bicarbonate lower than 10 mmol/L was significantly associated with hypophosphatemia. No complications associated with hypophosphatemia were observed.

Treatment of diabetic ketoacidosis with subcutaneous regular insulin in a non-ICU setting is effective and economical: A single-center experience

Treatment of diabetic ketoacidosis with subcutaneous regular insulin in a non-ICU setting is effective and economical: A single-center experience

Evaluation of blood glucose changes with regular versus rapid-acting insulin for hyperglycaemia management in the emergency department.

As emergency department (ED) visits secondary to hyperglycaemia increase, goals should focus on optimising treatment to minimise the length of stay (LOS). Both regular and rapid-acting insulins can effectively treat hyperglycaemia, but have different pharmacokinetic profiles. The purpose of this study is to compare blood glucose (BG) reduction over time in patients receiving subcutaneous regular versus rapid-acting insulin in the ED. This retrospective chart review from 1 January 2018 to 31 December 2020 included adult ED patients with a BG ≥200 mg/dl who received subcutaneous regular insulin or insulin aspart. The primary endpoint was a change in BG immediately before and ≥30 min after insulin administration over time. There were 279 patients included in the study (108 regular insulin and 171 insulin aspart). Change in BG over time was 41.5 mg/dl/h in the regular insulin group and 47 mg/dl/h in the insulin aspart group (P = 0.36). There was no difference in hypoglycaemic events, ED LOS, time from insulin administration to discharge and total change in BG during ED stay. Patients who received regular insulin required less additional insulin doses (8.3% vs. 18.1%, P = 0.02), received a greater volume of intravenous fluids (1629 ml vs. 1280 ml, P = 0.02) and higher weight-based dose for the first insulin dose (0.11 units/kg vs. 0.10 units/kg, P = 0.02). There was no significant difference in BG reduction between insulin types for hyperglycaemic patients treated in the ED. This suggests that regular insulin and rapid-acting insulin have similar efficacy in the treatment of hyperglycaemia in the ED.

Treatment of diabetic ketoacidosis with subcutaneous regular insulin in a non-ICU setting is effective and economical: A single-center experience

Background: The mainstay of treatment for diabetic ketoacidosis (DKA) is the correction of dehydration and hyperglycemia with intravenous fluids and intravenous insulin (IVI). Subcutaneous insulin (SCI) has been tried in a few centers in patients with DKA if the blood pH is &gt;7. In general, IVI is preferred over SCI or intramuscular insulin as its onset is rapid and the dose can be titrated based on patient’s varying blood glucose (BG) levels. However, IVI is associated with higher cost of hospitalizations and resource requirements. Thus, SCI could be an alternative to IVI infusion for DKA to reduce these costs and distress, in children during times of resource constraint such as the COVID-19 pandemic and in other resource-limited settings. Objective: The objective of the study was to compare the cost and efficacy of SCI therapy versus IVI infusion in the treatment of DKA. Materials and methods: A retrospective and cohort study was conducted among children aged 1–15 years admitted with DKA from 2013 to 2014 and treated with IVI and in 2017 treated with SCI at a tertiary hospital. One cohort was treated with IV infusion of regular insulin in intensive care units (ICU) and another cohort was treated with SC regular insulin in pediatric general wards. The main outcomes measured were the overall cost of hospitalization and hours to improvement in the child’s health. The data were analyzed with independent samples t-test with SPSS software. Results: Forty-eight patients admitted with 50 episodes of DKA were analyzed. Baseline characteristics of the two groups were similar in age, sex, BG, serum sodium, and HbA1C levels. The proportion of girls to boys was 13:8 (IV insulin group) and 20:9 (SC insulin group); the daily dose of insulin on day 1 of treatment was 1.2:1 unit/kg/day in IVI: SCI groups. The lowest recorded pH was 6.822 (range 6.822–7.154) and 6.831(range 6.831–7.292) in the IVI and SCI groups. The mean pH was 7.00 ± 0.10 and 7.1 ± 0.12, respectively, in IVI and SCI groups (P = 0.02). Episodes of DKA treated with IVI and SCI groups were 21 and 29, respectively. 23% of patients had severe DKA, 52% had moderate DKA, and 25% had mild DKA. The mean time for improvement in the IVI group was 34.95 ± 14.05 h and 17.23 ± 9.85 h in the SCI group (P = 0.001), respectively. The average cost of hospitalization was Rs. 53712 ± 18813 for IVI therapy and Rs. 14369 ± 5768 for SCI (P = 0.000). There were no major complications in the SCI group compared to the IVI group. Conclusion: DKA was managed effectively in general wards with SCI therapy with pH not being a limiting factor. Earlier studies have used SCI only in patients with a pH of &gt;7. Therapy with SCI was cost-effective and would be useful in resource-poor settings.

673-P: Successful Use of Dexcom G6 in Neonate with SGA and Chromosome 6q24-Related Transient Neonatal Diabetes Mellitus

Blood glucose in neonates with diabetes is variable due to frequent feeding, inexact exogenous insulin dosing and dynamic physiology. Rapid glucose fluctuation makes continuous glucose monitoring (CGM) ideal. We describe the successful use of CGM in an infant with small for gestational age (SGA) and chromosome 6q24-related transient neonatal diabetes mellitus, diagnosed by methylation study. A term male weighing 2650g (5th%) was born following uncomplicated pregnancy and delivery. Glucose checked per SGA-protocol revealed rising glucoses from initial 78 to &amp;gt;300 mg/dL over 24 hours. Hyperglycemia managed with insulin drip until transitioned to subcutaneous dilute regular insulin (U-concentration) administered q6 hours (every other feed) . Trial of sulfonylurea titrated to maximum dose was ineffective.Initially glucoses checked hourly while on insulin drip and transitioned to every 3 hours once on subcutaneous insulin. Dexcom G6 placed in lateral thigh without incident on DOL and impermeable dressing applied to prevent soiling.CGM values were generally within 10% of heelstick POC values though specific MARD was not calculated. In the 7 days prior to CGM placement, there were POC glucoses &amp;lt;80 mg/dL; in the 7 days after placement, there were none. Anecdotally, numerous times the CGM trend provided advanced notice of impending hypoglycemia and was able to be treated proactively (treatment decisions based on confirmatory heelstick) . The subject was discharged home on DOL 20.In followup, insulin degledec 0.5 unit/day was added and total prandial insulin requirements varied from 0-1 unit per day (total daily insulin dose approx. 0.1-0.3 units/kg/day) . By age 2.5 months weight was 6.1 kg (38th%) . CGM ambulatory glucose profile demonstrated mean glucose 185 mg/dL, &amp;lt;70 mg/dL &amp;lt;1%, 71-250 88%, &amp;gt;250 11%. In summary, Dexcom G6 CGM was successfully used in an infant with SGA and neonatal diabetes to optimize glucose control while minimizing hypoglycemia risk. Disclosure E.A. Los: Advisory Panel; Medtronic. K. Wise: None. J. Welsh: Employee; Dexcom, Inc.

Novel Route of Inhaled Insulin for Diabetes Treatment

Diabetes is a chronic condition characterised by insufficient insulin secretion and hyperglycemia as a result. Microvascular and macrovascular disease are two types of diabetic complications that are affected by good diabetes management. Many diabetics rely on subcutaneous insulin injections or continuous infusions to keep their blood sugar levels under control. Insulin delivery via new routes Since the 1920s, subcutaneous insulin has been used to treat diabetes; nevertheless, despite a variety of formulations, intensive insulin therapy including many daily injections has not acquired universal clinical approval. The search for a successful, well-tolerated nonenteral method for delivering insulin began in the 1920s, and has included ocular, buccal, rectal, vaginal, and other routes. Given that insulin injection therapy is burdensome for many patients, novel insulin administration routes are of interest in the diabetes sector. The use of inhalation to administer insulin to the lungs will be discussed in this review. Inhaled insulin's safety as well as efficacy in contrast to subcutaneous insulin in diverse diabetic populations are discussed. Until recently, many researchers considered that noninvasively given insulin had too low a bioavailability to be useful in clinical practise. Inhaled insulin, on the other hand, appears to be an effective, well-tolerated, and noninvasive alternative to subcutaneous regular insulin, according to a growing body of research. Importantly, inhaled insulin has a more physiological insulin profile than injectable insulin.

Subcutaneous regular insulin use for the management of diabetic ketoacidosis in resource limited setting.

The standard recommendation of insulin therapy for patients with DKA is the administration of slow continuous intravenous (IV) regular insulin. Currently subcutaneous insulin is being recommended as an alternative treatment of DKA in mild and moderate cases in resource-limited settings. The purpose of this study was to assess the effectiveness and safety of six-hourly subcutaneous regular insulin use for the treatment of DKA among children with type one diabetes mellitus. A retrospective cohort study was conducted among 224 DKA episodes which occurred in 161 children who were treated at St. Paul's Hospital Millennium Medical College in Addis Ababa, Ethiopia, from November 2015 to November 2020. Majority (68.8%) of the episodes occurred in newly diagnosed cases. The median time for urinary ketones clearance was 24h. DKA severity was found to be the only significant predictor of time to DKA resolution. Only 13 (5.8%) were treated at the pediatric intensive care unit (PICU), and 27 (12.1%) developed complications during management. No death or neurological complications observed. The six-hourly subcutaneous regular insulin use was found to be safe and effective alternative to slow IV insulin infusion for the treatment of DKA in a non PICU setting. As it resulted in minimum morbidity and no mortality, we recommend its use in the treatment of DKA irrespective of its severity. It can also decrease the health care cost and patients' inconvenience.

A Diabetic Woman with Insulin Injection Abscesses

A 50-year-old diabetic woman developed multiple abscesses after daily injections of subcutaneous regular human insulin. Initial cultures from the draining fluid revealed no organisms, and the patient was unresponsive to multiple courses of antibiotics including doxycycline, amoxicillin/clavulanic acid, and intravenous vancomycin and piperacillin/tazobactam. After consulting dermatology, the patient underwent punch biopsy and tissue culture. The tissue culture grew mycobacterium fortuitum after 22 days of incubation. The patient was diagnosed with non-tuberculous mycobacterial infection and began to improve after treatment with ciprofloxacin. Non-tuberculous mycobacteria are common in the environment, although systemic manifestations of infection are rare in healthy individuals. In this paper, we discuss the risk factors, diagnostic methods, and treatment recommendations for these types of infections.

Higher-Than-Conventional Subcutaneous Regular Insulin Doses Following Diabetic Ketoacidosis in Children and Adolescents

Objective:To evaluate the effect of initial insulin dosage on glycemic control in the first 48 hours of subcutaneous regular insulin therapy after resolution of diabetic ketoacidosis (DKA).Methods:Records of patients with DKA hospitalized in the past 3 years [n=76, median age=10.0 (6.0-12.0) years, Male/Female: 44/32] were reviewed. The patients were designated into two groups according to distribution of starting doses of subcutaneous insulin. Group 1 (n=28) received a median dose of 1.45 U/kg/day (1.41-1.5) and group 2 (n=48) a median dose of 0.96 U/kg/day (0.89-1). Clinical and laboratory data were analyzed.Results:Median, minimum, and maximum blood glucose levels of Group 1 in the first 48 hours of treatment were significantly lower than that of Group 2 [213 (171-242) vs. 255 (222-316), p=<0.001; 102 (85-151) vs. 129 (105-199), p=0.004; and 335 (290-365) vs. 375 (341-438), p=0.001, respectively]. The number of patients who experienced hypoglycemia (<70 mg/dL) were similar [Group 1, 5 (17.9%) vs. Group 2, 4 (8.3%), p=0.276] and none had severe hypoglycemia. In Group 1, the ratio of blood glucose levels within the target range (100-200 mg/dL) were higher (37.5% vs. 12.5%) and the number of results >200 mg/dL were lower (50% vs. 81.3%) compared to Group 2 (p=0.001 and p<0.001, respectively).Conclusion:After resolution of DKA, a higher initial dose of 1.4-1.5 U/kg/day regular insulin is associated with better glycemic control in children and adolescents without an increase in risk of hypoglycemia.

Hyperglycemia in critical patients: Determinants of insulin dose choice.

To identify factors that can determine the choice of intermittent subcutaneous regular insulin dose in critically ill patients with hyperglycemia. Cross-sectional study in a general adult ICU with 26 beds, data collected between September and October 2014. The variables analyzed were: sex, age, previous diagnosis of diabetes mellitus, use of corticosteroids, use of lactulose, sepsis, fasting, enteral nutrition, use of dextrose 5% in water, NPH insulin prescription and blood glucose level. Patients with one or more episodes of hyperglycemia (blood glucose greater than 180 mg/dL) were included as a convenience sample, not consecutively. Those with continuous insulin prescription were excluded from analysis. We included 64 records of hyperglycemia observed in 22 patients who had at least one episode of hyperglycemia. The median administered subcutaneous regular human insulin was 6 IU and among the factors evaluated only blood glucose levels were associated with the choice of insulin dose administered. Clinical characteristics such as diet, medications and diagnosis of diabetes mellitus are clearly ignored in the decision-making regarding insulin dose to be administered for glucose control in critically ill patients with hyperglycemia.

Subcutaneous regular insulin for the treatment of diabetic ketoacidosis in children.

Diabetic ketoacidosis (DKA) treatment protocols vary, however low-dose intravenous administration of regular insulin is the standard care for replacing insulin in most centers. Few studies, the majority in adults, demonstrated subcutaneous injection of rapid-acting insulin every 1-2 hours to be a valid alternative. To evaluate the efficacy and safety of subcutaneous regular insulin administered every 4 hours in pediatric DKA in a clinical setting. A retrospective chart review was conducted. Charts of all children treated with subcutaneous regular insulin for DKA and pH ≥ 7.0, between 2007 and 2010, were reviewed. Seventy-six DKA episodes in 52 patients were included. Data regarding clinical characteristics, response to treatment, and the occurrence of complications were analyzed. DKA episodes in patients with new-onset diabetes and in those with established diabetes were compared. Mean age was 11.6 ± 4.0 yr. Eighteen episodes occurred in children with new-onset diabetes. In all episodes, our protocol resulted in recovery from DKA. Median time to DKA resolution (pH > 7.30, HCO3 > 15) was 10.3 (5.5, 14.2) h. The median total insulin dose was 0.05 (0.04, 0.06) (unit/kg/h). During DKA treatment, hypoglycemia occurred in one episode and hypokalemia, mostly mild, was documented in 14. No cardiac arrhythmias, incidents of cerebral edema, or mortality occurred. Subcutaneous regular insulin administered every 4 hours is an effective and safe alternative for the insulin treatment of DKA with pH > 7.0 in children. Such treatment has the potential to simplify insulin administration when compared to either intravenous regular insulin or q1-2 hour subcutaneous rapid insulin and reduce both patient inconvenience and admission costs.

Simulation and qualitative analysis of glucose variability, mean glucose, and hypoglycemia after subcutaneous insulin therapy for stress hyperglycemia.

BackgroundThe critically ill can have persistent dysglycemia during the “subacute” recovery phase of their illness because of altered gene expression; it is also not uncommon for these patients to receive continuous enteral nutrition during this time. The optimal short-acting subcutaneous insulin therapy that should be used in this clinical scenario, however, is unknown. Our aim was to conduct a qualitative numerical study of the glucose-insulin dynamics within this patient population to answer the above question. This analysis may help clinicians design a relevant clinical trial.MethodsEight virtual patients with stress hyperglycemia were simulated by means of a mathematical model. Each virtual patient had a different combination of insulin resistance and insulin deficiency that defined their unique stress hyperglycemia state; the rate of gluconeogenesis was also doubled. The patients received 25 injections of subcutaneous regular or Lispro insulin (0-6 U) with 3 rates of continuous nutrition. The main outcome measurements were the change in mean glucose concentration, the change in glucose variability, and hypoglycemic episodes. These end points were interpreted by how the ultradian oscillations of glucose concentration were affected by each insulin preparation.ResultsSubcutaneous regular insulin lowered both mean glucose concentrations and glucose variability in a linear fashion. No hypoglycemic episodes were noted. Although subcutaneous Lispro insulin lowered mean glucose concentrations, glucose variability increased in a nonlinear fashion. In patients with high insulin resistance and nutrition at goal, “rebound hyperglycemia” was noted after the insulin analog was rapidly metabolized. When the nutritional source was removed, hypoglycemia tended to occur at higher Lispro insulin doses. Finally, patients with severe insulin resistance seemed the most sensitive to insulin concentration changes.ConclusionsSubcutaneous regular insulin consistently lowered mean glucose concentrations and glucose variability; its linear dose-response curve rendered the preparation better suited for a sliding-scale protocol. The longer duration of action of subcutaneous regular insulin resulted in better glycemic-control metrics for patients who were continuously postprandial. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units; if present, their clinical effects should be evaluated.

Peri operative diabetic management using subcutaneous regular insulin as sliding scale and alberti regimen of glucose insulin potassium infusion - comparative study

Background The management of diabetic patient during the peri-operative period can be a problem to the anaesthesiologist. Many of worker have used short acting regular insulin using sliding scale which starts before operation and continue in post operatively. Alberti and Thomas proposed a simple regimen using a cotinuous intravenous infusion of an glucose insulin potassium (GIK) solution which is administered during the prei-operative period. Objectives The aim of the study is to observe the rise of blood sugar in diabetic patients per and post operatively and to detrermine the more acceptable method of controlling blood sugar amongst two predetermined methods. Methods A total of 80 patients of ASA II &amp; III were randomly selected. They were divided into the following groups. Group A. forty patients were randomly allocated to the treatment of thrice daily subcutaneous injections of short acting regular insulin by sliding scale. Group B. Forty patients were randomly allocated to continuous glucose insulin potassium treatment (GIK). Pre-operative blood glucose was controlled with thrice daily subcutaneous injection of short acting regular insulin. Result The two groups were comparable in demographic data. The blood glucose of group A was raised at mid operation, after 8 hours, 16 hours and 24 hours of operation more than the group B and it were statistically significant. Serum potassium level of the two group did not show any significant difference. The study showed that group B can produce satisfactory blood sugar and serum potassium control than group A. It is safe, simple and less expensive and can be apply in any situation. Conclusion Due to the large number of diabetic patients undergoing surgery and probable complications associated with diabetes, careful perioperave evaluations and management are required in these patients. To select an appropriate interventional strategy depends on the patient, the associated diabetic complications and type of surgery. Chronic diabetic complications can influence surgery and anesthetic conditions. Hence, appropriate risk stratification, optimal blood glucose and suitable interventional strategy are necessary. Glucose insulin potassium infusion can minimize metabolic disturbances during surgery. DOI: http://dx.doi.org/10.3329/jbsa.v26i1.19816 Journal of Bangladesh Society of Anaesthesiologists 2013; 26(1): 45-51

Management of blood glucose during enteral nutrition in critical patients

To investigate an effective and safe protocol for enteral nutrition (EN) patients permitting successfully transmit insulin administration from venous pump-in to subcutaneous injection. A prospective randomized control study was conducted. Critical patients admitted to intensive care unit (ICU) of Beijing Tongren Hospital from September 2008 to February 2009 were randomly divided into two groups when the energy provided by EN up to half of the total energy requirement. Experiment group (n=44): the protocol was applied for insulin glargine and regular insulin injection; control group (n=43): protocol was applied for subcutaneous regular insulin injection. Target glucose range was 4.4-7.8 mmol/L (80-140 mg/dl). If blood glucose ≥11.1 mmol/L was maintained twicely, the approach of insulin administration would convert from subcutaneous injection to venous pump-in using the computerized glucose control protocol. If the infusion rate of insulin was less than 3 U/h and lasted more than 6 hours, blood glucose ≤7.8 mmol/L, insulin administration was switched to subcutaneous injection again. The general information and all glucose regulation data were recorded for analysis. The two groups did not differ at baseline for the general information, mean blood glucose and the glucose variation. A total of 1689 blood glucose records were analyzed. The mean blood glucose in experiment group, and was significantly lower than that in control group(7.58±1.17 mmol/L vs. 9.40±1.74 mmol/L, P<0.05). The rate of glucose values within target range in experiment group was significantly higher than that in control group [49.72% (534/1074) vs. 35.61% (219/615), P<0.01]. The glucose standard deviation (SD) in experiment group was significantly lower than that in control group (1.89±0.52 mmol/L vs. 2.17±0.94 mmol/L, P<0.05). The number of measurements needed per patient per day was significantly reduced in experiment group compared with control group (7.51±1.31 vs. 8.15±0.97, P<0.05). The ratio of patients converted to venous pump-in was significantly decreased in experiment group compared with control group (9.09% vs. 44.19%, P<0.01). Hypoglycemia (≤3.3 mmol/L) did not different between experiment group and control group [0.74% (8/1074) vs. 0.49% (3/615), P=0.75]. Compared with the conventional subcutaneous insulin injection protocol, this protocol with insulin glargine combined regular insulin subcutaneous injection can control the glucose level effectively during EN in critical patients. The glucose variation and the numbers of measurements were significantly reduced by this protocol. It is helpful for the insulin transmission from venous pump-in to subcutaneous injection.

Buccal insulin spray for prandial therapy of Type 1 and Type 2 diabetes

SUMMARY Current insulin therapy has some shortcomings, some related to the route of delivery. Subjects with diabetes are still reluctant to initiate/intensify insulin therapy or intentionally omit insulin injections. The buccal spray formulation represents an alternative way of insulin delivery, which offers the advantage of injection-free administration and an improved time-action profile with respect to subcutaneous regular human insulin. Data indicate that the buccal insulin spray is mostly absorbed and the main metabolic effect is obtained in the first 2 h after its application. This article reviews the data from clinical trials published so far, regarding the pharmacology, safety and efficacy and points out the advantages that this formulation may bring in clinical practice.

New Insulin Analogues and Perioperative Care of Patients with Type 1 Diabetes

While insulin remains the mainstay of managing type 1 diabetes, much has changed over the last 15 years. These changes should help in managing patients with type 1 diabetes during the perioperative period. More flexible insulin therapy has three components: (1) basal, (2) prandial and (3) corrective. Many patients, particularly younger patients, are using genetically modified recombinant human insulin analogues. Two of these analogues, aspart and lispro insulin, are rapid-acting with faster onset and offset than subcutaneous regular insulin, allowing both prandial and corrective boluses. Other insulin analogues, particularly glargine and possibly detemir have a flat profile of up to 24 hours, providing improved basal insulin delivery. Basal insulin can also be provided by a continuous subcutaneous infusion of rapid-acting insulin via a computerised pump that also provides boluses on demand. There is little evidence to help choose the best management of patients with type 1 diabetes during surgery. Some authors still recommend glucose-potassium-insulin infusions for all patients with type 1 diabetes. We challenge this approach, given the flexibility of the newer insulin analogues and delivery systems. We suggest that for many procedures, patients' usual regimens can be maintained in the perioperative period, providing less disruption and, possibly, greater safety. Both hyperglycaemia and hypoglycaemia reflect poor management: we suggest a target glucose range of 5 to 10 mmol/l. The importance of frequently measuring blood glucose and appropriate responses cannot be overemphasised.

The glucose lowering effect of an oral insulin (Capsulin) during an isoglycaemic clamp study in persons with type 2 diabetes

Randomized, open, single-centre, two-way crossover study comparing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of subcutaneous (sc) regular human insulin (Actrapid) and oral insulin in a capsule form (Capsulin). Sixteen persons (12 males) with type 2 diabetes on oral hypoglycaemic agents (OHAs) participated. Mean (s.d.) age 60.2 (5.5) years, BMI 28.3 (3.4) kg/m(2), haemoglobin A(1c) (HbA(1c)) 7.4% (1.1). Two 6-h isoglycaemic glucose clamp studies were conducted 11 days apart. All subjects received in random order 12U sc Actrapid on one clamp study day and either 150U or 300U Capsulin (Cap) on the other day. Glucose infusion rates (GIRs), plasma insulin and C-peptide concentrations were determined throughout each 6-h isoglycaemic clamp. Between the clamp study days, all patients received 150U Capsulin twice daily, dropping all their standard OHAs apart from metformin. Self-monitored blood glucose (SMBG) levels were taken four times a day between the clamp study days. Administration of either Actrapid or Capsulin (150 and 300U) increased GIRs reaching a maximum values at approximately 280-330 min. Overall values for maximum GIR values were higher for Actrapid than either dose of Capsulin (p < 0.05). The significantly greater systemic insulin concentrations following Actrapid were reflected in the AUC(0-6 h) (910 +/- 270 vs. 472 +/- 245 pmol h/L; 950 +/- 446 vs. 433 +/- 218 pmol h/L; both p < 0.05 for Actrapid vs. 150U Capsulin and 300U Capsulin respectively). No difference was observed between 150U and 300U Capsulin. During the repeat-dosing period, good safety and tolerability were observed with Capsulin, and SMBG levels remained stable. At the poststudy visit, significant falls in HbA(1c), weight and triglycerides were observed. Administration of the oral insulin Capsulin preparation demonstrated a significant hypoglycaemic action over a period of 6 h associated with only a small increase in circulating plasma insulin concentrations.

PROMAXX® inhaled insulin: safe and efficacious administration with a commercially available dry powder inhaler

We investigated the pharmacokinetic (PK) and pharmacodynamic (PD) properties of recombinant human insulin inhalation powder (RHIIP), manufactured with PROMAXX technology, which allows formation of uniform protein microspheres. Thirty healthy male subjects [age 30 +/- 1 years (mean +/- s.e.), body mass index 24.2 +/- 0.3 kg/m(2)] in a randomized crossover study received 10 IU subcutaneous regular human insulin (SCIns) and 6.5 mg of RHIIP [187 IU, Cyclohaler dry powder inhaler (DPI)] under euglycaemic glucose clamp conditions. Subjects were trained to inhale RHIIP with a flow rate of 90 +/- 30 l/min prior to dosing. Inhalation of RHIIP was well tolerated with no episode of cough or shortness of breath. RHIIP showed a faster onset of action than SCIns [time to reach 10% of total area under the glucose infusion rate (GIR) curves 73 +/- 2 vs. 95 +/- 3 min, time to maximal metabolic effect (T(max)GIR) 173 +/- 13 vs. 218 +/- 9 min, both p < 0.0001]. Duration of action (371 +/- 11 vs. 366 +/- 7 min) and total metabolic effect (AUCGIR0-10 h 2734 +/- 274 vs. 2482 +/- 155 mg/kg) were comparable. PK results were in accordance with the PD findings. Relative bioavailability (BA) of RHIIP was 12 +/- 2%, and relative biopotency (BP) was 6 +/- 1%. PROMAXX technology allowed for safe and efficacious administration of RHIIP to the deep lung with an off-the-shelf DPI. RHIIP showed a fast onset of action and BA/BP comparable to that reported for other inhaled insulin formulations using specifically designed inhalers. Improvements in the insulin delivery technique might allow to optimize drug application in all cases with even higher BA/BP with RHIIP.

An oral sulfonylurea in the treatment of transient neonatal diabetes mellitus

Background: Neonatal diabetes mellitus (NDM) is rare, with a prevalence of ∼1 in 500,000 infants worldwide. NDM may be caused by several different genetic abnormalities, and might either be transient (TNDM) or permanent. Until recently, clinical management of most permanent types of NDM required lifelong subcutaneous insulin treatment. However, due to activating mutations in the genes that encode the adenosine triphosphate—sensitive K+ channel, some permanent types of NDM have been found to be amenable to oral sulfonylurea therapy. TNDM can last for a median of 12 weeks and completely resolve by 18 months. Although TNDM is typically treated with subcutaneous insulin, this mode of therapy might be difficult for some caregivers.Case summary: A small for gestational age male infant born at term developed NDM on day of life (DOL) 3. No other factors, such as sepsis, infection, or dextrose-containing intravenous fluids, that could have accounted for the hyperglycemia were present. In addition, there was no family history of DM or hyper-glycemic disorders. The patient was initially treated with subcutaneous regular insulin (0.25 U at a concentration of 10 U/L) q4h PRN for blood glucose concentrations >200 mg/dL. However, due to persistent blood glucose concentration fluctuations, a continuous insulin infusion (0.05 U/kg/h) was started on DOL 7. Because subcutaneous insulin injections could not be administered by the parents outside of the hospital, oral sulfonylurea therapy was attempted. A glyburide oral suspension, prepared by dissolving half of a 1.25-mg tablet in 1 mL of preservative-free, sterile water, was started at 0.2 mg/kg/d in 2 divided doses. The suspension was prepared immediately prior to each dose and was administered via syringe during feedings. On DOL 21, the patient's NDM was managed solely with an oral sulfonylurea, target blood glucose concentrations of 150 to 250 mg/dL were achieved with glyburide 0.7 mg/kg/d in 2 divided doses, and insulin administration was no longer required. On DOL 25, the glyburide dosage was decreased to 0.5 mg/kg/d in 2 divided doses. On DOL 27, the patient was discharged on the same dosage. The patient's NDM subsequently resolved by DOL 49.Conclusion: An oral sulfonylurea was a useful treatment option in the management of TNDM in this patient.

Pharmacokinetics and Pharmacodynamics of Intranasal Insulin Spray (Nasulin™) Administered to Healthy Male Volunteers: Influence of the Nasal Cycle

The pharmacokinetics and pharmacodynamics of a Bentley Pharmaceuticals proprietary intranasal (IN) insulin formulation (Nasulin) were studied in healthy volunteers. Thirteen fasting healthy male volunteers received five doses of medication (one dose of 4 international units [IU] subcutaneous (SC) regular insulin and four doses of 25 IU IN insulin) at least 48 h apart. Serum insulin, serum C-peptide, and plasma glucose were measured in the 4 h after dosing. Profiles were compared for IN insulin spray following administration into the dominant nostril (more open at time of dosing) and into the nondominant nostril (less open at time of dosing). The formulation was generally well tolerated. A rise in serum insulin levels accompanied by a decrease in plasma glucose was seen following all doses. For IN doses, peak insulin levels were generally attained in 10-20 min and remained elevated for approximately 40-50 min; the resultant effect on glucose peaked at 40 min and waned approximately 2 h postdosing. As reported in other studies, the interindividual response to insulin was variable. The comparative absorption of IN insulin relative to SC insulin was 12.0% (dominant nostril) or 15.4% (nondominant nostril) over 2 h. This increased somewhat if sneezers and volunteers with moderately blocked nostrils were removed from the analysis. This IN formulation was generally well tolerated and relatively well absorbed. While both insulin data (maximal plasma concentration and area under the plasma concentration time curve) and glucose data (% fall) support a trend toward better absorption from the nondominant nostril, this did not reach statistical significance. Nasulin can be administered without reference to the nasal cycle.