Continuous Insulin Administration Research Articles

SUN-141 Vitamin D Status and Diabetic Control in Children with Type 1 Diabetes Mellitus

Vitamin D insufficiency is common among children and adolescents, particularly among those with type 1 diabetes mellitus (T1DM). Studies of patients with type 2 diabetes mellitus (T2DM) indicated that treatment of vitamin D deficiency improved glycemic control (Nada & Shaheen, 2017). Additional studies reviewed by Peterson et al. (2014) indicated an association between vitamin D status and insulin sensitivity among obese adolescents. Other studies have investigated the effect of vitamin D on glycemic control in patients with T1DM, but little data is available about insulin sensitivity and vitamin D levels in patients with T1DM. We investigated the association between vitamin D status and diabetes control in children with T1DM. Our study was a retrospective chart review of subjects with T1DM ages 2-21 years evaluated in our pediatric diabetes clinic over the past eight years. We looked specifically at the relationship between vitamin D status, insulin requirement and Hb A1C (A1C). Inclusion criteria were: continuous insulin administration using a pump, at least two determinations of serum levels of 25-hydroxy vitamin D, frequent blood glucose (BG) monitoring and regular follow-up in our diabetes clinic. Patients were included if they had been diagnosed with diabetes for at least 11 months prior to the study, and required ≥ 0.49 units of insulin/kg/day. Subject demographics, A1C levels, and BG levels were recorded. Average daily insulin dose and vitamin D level determined at the corresponding clinic visit were also recorded. Data were analyzed using IBM SPSS statistical software version 24. Thirty-one patients were included in the study, ranging in age from 2.6-17.4 years old. Sixteen subjects (52%) were female and 15 subjects (48%) were male. The proportion of patients whose A1C values improved corresponded to a change in 25-hydroxyvitamin D of ≥ 7.5 ng/mL. An increase in the vitamin D level was associated with a statistically significant decrease in insulin requirement. Our findings suggest that optimization of vitamin D status in patients with T1DM may reduce insulin requirements and improve glycemic control. Reference: 1. Nada et al., Ther Clin Risk Manag. 2017 Jul 7;13:813-820 2. Peterson et al., Ther Adv Endocrinol Metab. 2014 Dec;5(6):166-89

Respiratory failure in a diabetic ketoacidosis patient with severe hypophosphatemia.

Phosphate is essential in regulating human metabolic processes, and severe hypophosphatemia can induce neurologic and hematological complications and result in respiratory failure and cardiac dysfunction. Therefore, correction of severe hypophosphatemia can be pivotal in the management of diabetic ketoacidosis (DKA). We report the case of a 14-year-old female who was diagnosed with type 1 diabetes and referred to our institute for treatment of DKA. Although the patient received fluid and continuous insulin administration according to the current DKA treatment protocol, generalized tonic seizures and cardiac arrest developed. After cardiopulmonary resuscitation, the patient recovered and was stable. Within 16 hours after DKA treatment, the patient developed respiratory failure with severe hypophosphatemia that required mechanical ventilation. Concurrent neurologic evaluation revealed no specific abnormalities. The patient recovered without any complications after correcting the hypophosphatemia. We suggest vigilant monitoring of the phosphate level in DKA patients and active replacement when required.

Impact of the Type of Continuous Insulin Administration on Metabolism in a Diabetic Rat Model

Exogenous insulin is the only treatment available for type 1 diabetic patients and is mostly administered by subcutaneous (SC) injection in a basal and bolus scheme using insulin pens (injection) or pumps (preimplanted SC catheter). Some divergence exists between these two modes of administration, since pumps provide better glycaemic control compared to injections in humans. The aim of this study was to compare the impacts of two modes of insulin administration (single injections of long-acting insulin or pump delivery of rapid-acting insulin) at the same dosage (4 IU/200 g/day) on rat metabolism and tissues. The rat weight and blood glucose levels were measured periodically after treatment. Immunostaining for signs of oxidative stress and for macrophages was performed on the liver and omental tissues. The continuous insulin delivery by pumps restored normoglycaemia, which induced the reduction of both reactive oxygen species and macrophage infiltration into the liver and omentum. Injections controlled the glucose levels for only a short period of time and therefore tissue stress and inflammation were elevated. In conclusion, the insulin administration mode has a crucial impact on rat metabolic parameters, which has to be taken into account when studies are designed.

Continuous insulin administration via complex central venous catheter infusion tubing is another risk factor for blood glucose imbalance. A retrospective study

BackgroundWe assessed the potential impact of infusion tubing on blood glucose imbalance in ICU patients given intensive insulin therapy (IIT). We compared the incidence of blood glucose imbalance in patients equipped, in a nonrandomized fashion, with either conventional tubing or with a multiport infusion device.MethodsWe retrospectively analyzed the nursing files of 35 patients given IIT through the distal line of a double-lumen central venous catheter. A total of 1389 hours of IIT were analyzed for occurrence of hypoglycemic events [defined as arterial blood glucose below 90 mg/dL requiring discontinuation of insulin].ResultsTwenty-one hypoglycemic events were noted (density of incidence 15 for 1000 hours of ITT). In 17 of these 21 events (81%), medication had been administered during the previous hour through the line connected to the distal lumen of the catheter. Conventional tubing use was associated with a higher density of incidence of hypoglycemic events than multiport infusion device use (23 vs. 2 for 1,000 hours of IIT; rate ratio = 11.5; 95% confidence interval, 2.71–48.8; p < 0.001).ConclusionsThe administration of on-demand medication through tubing carrying other medications can lead to the delivery of significant amounts of unscheduled products. Hypoglycaemia observed during IIT could be related to this phenomenon. The use of a multiport infusion device with a limited dead volume could limit hypoglycemia in patients on IIT.

Systems Initiatives Reduce Healthcare-Associated Infections: A Study of 22,928 Device Days in a Single Trauma Unit

"Implementation research" promotes the systematic conversion of evidence-based principles into routine practice to improve the quality of care. We hypothesized a system-based initiative to reduce nosocomial infection would lower the incidence of ventilator-associated pneumonia (VAP), urinary tract infection (UTI), and bloodstream infection (BSI). From January 2006 to April 2008, 7,364 adult trauma patients were admitted, of which 1,953 (27%) were admitted to the trauma intensive care unit and comprised the study group. Tight glycemic control was maintained using a computer algorithm for continuous insulin administration based on every 2-hour blood glucose testing. Centers for Disease Control and Prevention definitions of nosocomial infections were used. Evidence-based infection reduction strategies included the following: a VAP bundle (spontaneous breathing, Richmond Agitation-Sedation Scale, oral hygiene, bed elevation, and deep vein thrombosis/stress ulcer prophylaxis), UTI (expert insertion team and Foley removal/change at 5 days), and BSI (maximum barrier precautions, chlorhexidine skin prep, line management protocol). An electronic dashboard identified the at-risk population, and designated auditors monitored the compliance. Infection rates (events per 1,000 device days) were measured over time and compared annually using Fisher's exact test. The study group had 22,928 device exposure days: 6,482 ventilator days, 9,037 urinary catheter days, and 7,399 central line days. Patient acuity, demographics, and number of device days did not vary significantly year-to-year. Annual infection rates declined between 2006 and 2008, and decreases in UTI and BSI rates were statistically significant (p < 0.05). These decreases pushed UTI and BSI rates below Centers for Disease Control and Prevention norms. Over 28 months, a systems approach to reducing nosocomial infection rates after trauma decreased nosocomial infections: UTI (76.3%), BSI (74.1%), and VAP (24.9%). Our experience suggests that infection reduction requires (1) an evidence-based plan; (2) MD and staff education/commitment; (3) electronic documentation; and (4) auditors to monitor and ensure compliance.

Comparison of the priming effects of pulsatile and continuous insulin delivery on insulin action in man

Insulin is normally secreted in man in regular pulses every 5 to 15 minutes. Disordered pulsation has been demonstrated in several insulin-resistant states and it is unclear whether this represents a primary beta-cell defect contributing to impairment of peripheral insulin action or rather is a consequence of insulin resistance. Basal or near basal insulin administration by pulsatile infusion augments hypoglycemic effect and improves insulin-mediated glucose uptake compared with insulin by continuous infusion. To date no study has examined whether normal basal insulin pulsatility is required to preserve subsequent insulin sensitivity during hyperinsulinemia. We studied the effect of overnight pulsatile versus continuous basal insulin on a subsequent hyperinsulinemic euglycemic clamp. Nineteen normal volunteers (male:female ratio, 17:2; mean age ± SEM, 26.1 ± 2.3 years) were studied on 2 occasions each. Endogenous insulin secretion was inhibited by octreotide (0.43 μg kg −1 · h −1) and replaced overnight at 5.4 mU kg −1 · h −1 either by continuous infusion or in 2-minute pulses every 13 minutes (n = 10) or every 7 minutes (n = 9). Glucagon was replaced at physiological concentration by continuous infusion (30 ng · kg −1 · h −1). Venous plasma glucose overnight was not significantly different between the pulsatile and continuous protocols. After discontinuing the overnight insulin infusion, insulin action was assessed during a hyperinsulinemic euglycemic clamp (1 mU kg −1 · h −1). Glucose infusion rates at steady-state during the hyperinsulinemic clamp were similar between continuous and both frequencies of pulsatile infusion (continuous 44.6 ± 4.3 μmol · kg −1 · min −1 v 13-minute pulsatile 41.7 ± 5.9 μmol · kg −1 · min −1, P = .27; continuous 34.6 ± 2.5 μmol · kg −1 min −1 v 7-minute pulsatile 41.4 ± 3.2 μmol · kg −1 · min −1, P = .08). We conclude that overnight pulsatile compared with continuous insulin administration has no different effect on subsequent peripheral insulin-mediated glucose uptake. A priming effect cannot therefore explain the previously demonstrated association between endogenous insulin pulse frequency and peripheral insulin action.

Effects of Insulin Administration in Diabetic Rats on Food and Drink Rhythmic Schedules

In normal rats food and water intakes are associated in terms of time and quantity and their diurnal rhythms are synchronized. Intake behavior in streptozotocin-induced diabetic rats (ID) with marked polyphagia and polydipsia and in diabetic rats with continuous insulin administration (IT) has been studied. The daily percentages of food and water intakes during the dark phase were lower in IT than in control rats (C), being even lower in ID rats. However, all three groups showed circadian rhythmicity in food intake, although with less amplitude in the ID and IT animals compared to the C ones. A loss of the normal circadian rhythm of water intake was observed in the ID rats and although the insulin administration recovered circadian rhythmicity, it did not restore the temporal relations between food and water intakes. These results may indicate that the circadian pattern of water intake is more influenced by insulin than food intake. The daily pattern of this hormone may play an important role in the circadian modulation of the homeostatic mechanisms integrating both intake behaviors.

Lack of Evidence for Improvement in Long-Term Glycemic Control by Pulsatile Insulin Infusion in Streptozocin-Induced Diabetic Baboon

To assess the potential therapeutic use of pulsatile intravenous insulin delivery, five streptozocin-induced diabetic baboons were treated with alternate 3- to 6-wk periods of pulsatile and continuous insulin infusion. Time-averaged insulin concentrations were matched during two pulsatile administration periods (P1 and P2) and an intervening period of continuous insulin administration (C). There were no significant differences among the overall means of four daily glucose determinations performed during the three periods (P1, 5.7 +/- 1 mM; C, 5.6 +/- 0.9 mM; P2, 5.3 +/- 0.9 mM); the mean M value, a measure of the stability of glycemic control (P1, 4 +/- 1.7; C, 3.9 +/- 1.8; P2, 3.6 +/- 1.5); the percentage of glucose values less than 2.8 mM (P1, 13 +/- 8.5%; C, 14 +/- 12%; P2, 13 +/- 9.1%); or the glycosylated hemoglobin levels determined at the end of the P1 and C (7.5 +/- 3.4 and 6.5 +/- 1.8%, respectively [all values are means +/- SD]). Fasting hepatic glucose production was suppressed to a similar degree during pulsatile and continuous insulin infusion (P1, 23 +/- 3 mumol.kg-1.min-1; C, 24 +/- 8 mumol.kg-1.min-1). Arterial glucagon levels were similar during pulsatile and continuous insulin infusion, both in the fasting state (84 +/- 29 and 84 +/- 31 ng/L, respectively) and postprandially (30 +/- 14 and 27 +/- 12 ng/L, respectively). Pulsatile insulin infusion failed to entrain a corresponding glucagon secretory rhythm. These data suggest that the metabolic consequences of long-term pulsatile and continuous insulin infusion in an animal model of human non-insulin-dependent diabetes are comparable.

Advantageous metabolic effects of pulsatile insulin delivery in noninsulin-dependent diabetic patients.

This study was done to compare the actions of pulsatile and continuous insulin administration in eight noninsulin-dependent diabetic patients. Human insulin was delivered in a pulsatile manner (1.3 mU/kg.min for 2 min, followed by 11 min during which no insulin was infused) or continuously (0.2 mU/kg.min) for 325 min. Endogenous hormone secretion was inhibited by somatostatin (125 micrograms/h), and glucagon was replaced at rate of 3.5 micrograms/h. Under these conditions plasma C-peptide levels fell progressively to extremely low values at the end of the experiment. Continuous insulin infusion resulted in steady plasma insulin levels, averaging 86 pmol/L, while during intermittent insulin administration plasma insulin levels were 5.7 and 158 pmol/L before and 3 min after the start of the insulin injection, respectively. Basal plasma glucagon [mean 158 +/- 11 (+/- SE) vs. 163 +/- 21 ng/L; P = NS] levels were similar on both occasions. During replacement peripheral plasma glucagon levels were no different whatever the mode of insulin administration, nor did they differ from the basal values. The mean plasma glucose concentrations were similar before both studies and rose to 9.5 and 8.6 mmol/L in the first 65 min during continuous and pulsatile insulin administration, respectively. In contrast, during the last 65 min, plasma glucose averaged 6.2 mmol/L during both studies. The glucose infusion rate initially increased, but then rapidly fell to values close to zero at the end of the first 65 min during the continuous insulin infusion, whereas during this time it averaged 0.59 +/- 0.10 mg/kg.min (32.5 +/- 5.5 mumol/kg.min) during pulsatile insulin administration. In the last 65 min the glucose infusion rate was significantly higher during pulsatile than during continuous insulin delivery. Furthermore, pulsatile rather than continuous insulin administration significantly reduced plasma triglyceride, very low density lipoprotein triglyceride, and FFA levels and increased high density lipoprotein cholesterol and apolipoprotein-B levels. We conclude that pulsatile insulin delivery has advantageous metabolic effects compared to continuous hormone administration in patients with noninsulin-dependent diabetes mellitus.

Efficacy of pulsatile versus continuous insulin administration on hepatic glucose production and glucose utilization in type I diabetic humans.

To evaluate the role of pulsatile insulin administration, hepatic glucose production (HGP) and utilization were studied in type I diabetic patients in the fasting state and during a euglycemic insulin (1 mU X kg-1 X min-1 i.v.) clamp with continuous and pulsatile insulin administration. In the latter study, insulin was infused at twice the continuous rate with 3-min-on/7-min-off intervals, thereby reducing total insulin delivery by 40%. The restraining effect of pulsatile insulin on basal HGP (1.91 +/- 0.35 mg X kg-1 X min-1) was equipotent to continuous insulin exposure (1.80 +/- 0.17 mg X kg-1 X min-1). During the insulin-clamp studies, HGP was equally suppressed by pulsed (0.62 +/- 0.12 mg X kg-1 X min-1) as by continuous insulin infusion (0.63 +/- 0.12 mg X kg-1 X min-1). Insulin-stimulated glucose utilization was not significantly altered in either study (2.55 +/- 0.27 vs. 2.92 +/- 0.23 mg X kg-1 X min-1). When in further studies the total insulin dose given during the pulsatile study was infused continuously (0.6 mU X kg-1 X min-1), HGP in the basal state and residual HGP during the insulin-clamp study were 25-30% higher than in the pulsatile experiments, whereas glucose utilization was not significantly different. In conclusion, by reducing total hormone delivery by up to 40%, but given in a pulsatile fashion, insulin is equally potent in controlling HGP as continuous insulin administration. This greater efficacy of pulsatile exposure in suppressing HGP is accompanied by an equipotent effect on glucose utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of pulsatile versus continuous insulin administration on hepatic glucose production and glucose utilization in type I diabetic humans

Efficacy of pulsatile versus continuous insulin administration on hepatic glucose production and glucose utilization in type I diabetic humans

Studies on the pathogenesis of the dawn phenomenon in insulin-dependent diabetic patients

To assess the role of hormonal factors in the pathogenesis of the dawn phenomenon, nocturnal (9:00 pm to 9 am) concentrations of blood glucose, free insulin, and counterregulatory hormones were determined in eight insulin-dependent diabetic patients under feedback-controlled and continuous insulin infusions after previous blood glucose normalization. Under feedback control, mean insulin requirements, necessary for maintenance of euglycemia rose significantly in the early morning (11:00 pm to 3 am: 8.4 ± 1.4; 5 am to 9 am: 12.6 ± 1.5 mU/kg/h; P < 0.01). Mean free-insulin concentrations did not increase simultaneously. Correspondingly, mean insulin-clearance rates under continuous insulin infusion were higher in the morning (11:00 am to 3 am: 359 ± 58; 5 am to 9 am: 459 ± 72 mL/min/m 2; P < 0.05). Increases of insulin clearance rates were most marked (>15%) in patients whose blood glucose rose during continuous insulin administration. Glucagon and norepinephrine concentrations were stable throughout both parts of the study. Cortisol and growth hormone exhibited the known nocturnal rhythms. Epinephrine levels were at the lower limit of detection at night and rose to normal basal concentrations at 9:00 am. We conclude that increases of insulin clearance rates may be an important factor for the development of the dawn phenomenon while the role of most counter-regulatory hormones is still uncertain.

Artificial Devices for Continuous Insulin Administration: An Outlook

Artificial Devices for Continuous Insulin Administration: An Outlook