Subcutaneous Insulin Treatment Research Articles

Effects of subcutaneous vs. oral nanoparticle-mediated insulin delivery on hemostasis disorders in type 1 diabetes: A rat model study

Complications associated with Type 1 diabetes (T1D) have complex origins that revolve around chronic hyperglycemia; these complications involve hemostasis disorders, coagulopathies, and vascular damage. Our study aims to develop innovative approaches to minimize these complications and to compare the outcomes of the new approach with those of traditional methods. To achieve our objective, we designed novel nanoparticles comprising covalent organic frameworks (nCOF) loaded with insulin, termed nCOF/Insulin, and compared it to subcutaneous insulin to elucidate the influence of insulin delivery methods on various parameters, including bleeding time, coagulation factors, platelet counts, cortisol plasma levels, lipid profiles, and oxidative stress parameters. Traditional subcutaneous insulin injections exacerbated hemostasis disorder and vascular injuries in streptozotocin (STZ)-induced diabetic rats through increasing plasma triglycerides and lipid peroxidation. Conversely, oral delivery of nCOF/Insulin ameliorated hemostatic disorders and restored the endothelial oxidant/antioxidant balance by reducing lipid peroxidation and enhancing the lipid profile. Our study pioneers the understanding of how STZ-induced diabetes disrupts bleeding time, induces a hypercoagulable state, and causes vascular damage through lipid peroxidation. Additionally, it provides the first evidence for the involvement of subcutaneous insulin treatment in exacerbating vascular and hemostasis disorders in type 1 diabetes (T1D). Introducing an innovative oral insulin delivery via the nCOF approach represents a potential paradigm shift in diabetes management and patient care and promises to improve treatment strategies for type 1 Diabetes.

THU324 Euglycemic Diabetic Ketoacidosis Coinciding With COVID-19 Infection During Pregnancy

Abstract Disclosure: M. Alkhathlan: None. A. Siddiqui: None. Background: Pregnancy is well known to be a diabetogenic and ketogenic state. When coinciding with an acute illness like COVID-19 infection, it can lead to full-blown DKA requiring intervention to reverse ketoacidosis. Complete restoration of normal glycemic status can be achieved after treatment of COVID-19 infection. Clinical case: A 34-year-old, G3 P2 woman who was at 26 weeks gestation with triplet pregnancy presented to the ED with fever, shortness of breath, nausea and vomiting for 3 days. She had gestational hypertension and impaired glucose tolerance during her previous pregnancy, but none during her current pregnancy. She had tested positive for COVID-19 infection at an outpatient evaluation for mild upper respiratory symptoms, two days prior to her presentation. Vital signs in the ER were T 35.3 °C, RR 22, HR 103, BP 121/70, and O2 sat 95% on 4 L/min nasal cannula. Initial laboratory testing showed sodium 132 (135-145), potassium 4.4 (3.5-5.5), bicarb 9 mmol/L (22-29), anion gap 18 mmol/L (5-14), BUN 3 mg/dL (6-23), creatinine 0.43, eGFR > 60, glucose 113 mg/dL (74-109), serum ketones 3.13 mmol/L (0.02-0.27) and lactate 1.6 mmol/L (0.5-2.5). ABG confirmed acidosis with pH of 7.29, and PCO2 was 22. She was diagnosed with euglycemic DKA after ruling out other possible etiologies of high anion gap metabolic acidosis. She received betamethasone by the Obstetrics team and fetal monitoring was initiated. DKA treatment was started with IV insulin, dextrose and close glucose monitoring. She had complete resolution of metabolic acidosis after 34 hours and did not require subcutaneous insulin treatment post-DKA resolution. She was able to tolerate oral diet with significant improvement of all her symptoms. She required only supportive treatment for COVID-19 infection and tested negative on the third day of hospitalization. Conclusion: Pregnancy is a ketogenic state and when superimposed with a significant acute illness of COVID-19, can lead to euglycemic DKA even in the absence of gestational diabetes. Early detection and treatment of ketoacidosis with COVID-19 is critical to avoid fetal and maternal complications or premature delivery. Presentation: Thursday, June 15, 2023

A comparative study using insulin pump therapy and continuous glucose monitoring in newly diagnosed very young children with type 1 diabetes: it is possible to bend the curve of HbA1c.

The target of metabolic control (HbA1c < 7% or 53mmol/mol) recommended by the ADA and ISPAD is attained by 30% of children with Type 1 Diabetes (T1D). Advances in technologies for T1D aim to improve metabolic outcomes and reduce complications. This observational study assesses the long-term outcomes of advanced technologies for treatment of T1D compared to conventional approach started at onset in a group of very young children with T1D. 54 patients with less 4years old at onset of T1D were enrolled and followed for up to 9years after diagnosis. 24 subjects started continuous subcutaneous insulin (CSII) treatment and 30 subjects received MDI therapy from onset. Auxological data, HbA1c and total daily insulin dose (TDD/kg) have been collected at admission and every 4months. HbA1cAUC>6%, rates of acute complications, glycemic variability indices and glucometrics were also recorded. Patients with CSII therapy had significantly lower mean HbA1c values compared to subjects receiving MDI treatment. CSII approach also recorded lower mean HbA1cAUC>6% and TDD/kg than MDI therapy. At the last download data, the time in range (TIR) was higher in patients with CSII and hyperglycemia events were lower. Better glycemic variability indices have been described during CSII therapy, including mean glycemia, standard deviation, coefficient of variation (CV), glycemia risk index (GRI) and high blood glucose index (HBGI). There was no statistically significant difference between frequency of severe hypoglycemia and ketoacidosis episodes between groups. Early initiation of diabetes technologies is safe and able to determine a better long term glycemic control in young children with T1D. It also allows to flatten the trajectory of HbA1c, probably reducing microvascular, macrovascular and neurological complications of diabetes in this very peculiar age group.

Abstract #1493875: Efficacy and Safety of Short-term Continuous Subcutaneous Native GLP-1 Infusion Versus Intensive Insulin (CSII) Treatment in Patients with Newly Diagnosed Type 2 diabetes

Abstract #1493875: Efficacy and Safety of Short-term Continuous Subcutaneous Native GLP-1 Infusion Versus Intensive Insulin (CSII) Treatment in Patients with Newly Diagnosed Type 2 diabetes

Dysregulated growth hormone-insulin-like growth factor-1 axis in adult type 1 diabetes with long duration.

In type 1 diabetes (T1D), dysregulation of the GH-IGF-1 axis has been reported. Whether this is related to upper extremity impairments (UEI) is unknown. Examine differences in GH-IGF-1 axis between T1D on subcutaneous insulin treatment and matched controls without diabetes and possible associations between GH-IGF-1 axis and UEI. Cross-sectional population-based study. Patients with T1D, onset <35years, duration ≥ 20years, <67years old and controls were invited to answer questionnaires and take blood samples. A total of 605 patients with T1D and 533 controls accepted to participate. Fasting levels of IGF-1, IGF-1 Z-score, IGFBP-1, IGFBP-3, C-peptide, GH and UEI. Patients with T1D had lower IGF-1 and IGFBP-3 and higher IGFBP-1 and GH than controls. The difference in IGF-1 persisted with age. Insulin dose was associated with increasing IGF-1 Z-score but even at a very high insulin dose (>1U/kg) IGF-1 Z-score was subnormal compared to controls. IGF-1 Z-score was unaffected by glycaemic control (HbA1c) but increased with residual insulin secretion, (C-peptide 1-99 pmol/L). IGFBP-1 was associated with fasting blood glucose, negatively in controls and positively in patients with T1D probably reflecting insulin resistance and insulin deficiency, respectively. There was no association between lower IGF-1 Z-score and UEI in T1D. In adult T1D with fair glycaemic control, the GH-IGF-1 axis is dysregulated exhibiting GH resistance, low IGF-1 and elevated IGFBP-1. Subcutaneous insulin cannot normalize these changes while endogenous insulin secretion has marked effects on IGF-1 pointing to a role of portal insulin.

Combined treatment with melatonin and insulin improves glycemic control, white adipose tissue metabolism and reproductive axis of diabetic male rats

AimsMelatonin treatment has been reported to be capable of ameliorating metabolic diabetes-related abnormalities but also to cause hypogonadism in rats. We investigated whether the combined treatment with melatonin and insulin can improve insulin resistance and other metabolic disorders in rats with streptozotocin-induced diabetes during neonatal period and the repercussion of this treatment on the hypothalamic-pituitary-gonadal axis. Main methodsAt the fourth week of age, diabetic animals started an 8-wk treatment with only melatonin (0.2 mg/kg body weight) added to drinking water at night or associated with insulin (NHP, 1.5 U/100 g/day) or only insulin. Animals were then euthanized, and the subcutaneous (SC), epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Hypothalamus was collected for gene expression and blood samples were collected for biochemical assays. Key findingsThe treatment with melatonin plus insulin (MI) was capable of maintaining glycemic control. In epididymal (EP) and subcutaneous (SC) adipocytes, the melatonin plus insulin (MI) treatment group recovered the insulin responsiveness. In the hypothalamus, melatonin treatment alone promoted a significant reduction in kisspeptin-1, neurokinin B and androgen receptor mRNA levels, in relation to control group. SignificanceCombined treatment with melatonin and insulin promoted a better glycemic control, improving insulin sensitivity in white adipose tissue (WAT). Indeed, melatonin treatment reduced hypothalamic genes related to reproductive function.

Transition from intravenous insulin to subcutaneous long-acting insulin in critical care patients on enteral or parenteral nutrition

Background and aimsThe optimal initial dose of subcutaneous (SC) insulin after intravenous (IV) infusion is controversial, especially in patients receiving continuous enteral nutrition (EN) or total parenteral nutrition (TPN). The aim of this study was to evaluate the strategy used at our hospital intensive care unit (ICU) in patients switched from IV insulin to SC insulin glargine while receiving EN or TPN. Design and methodsA retrospective analysis was made of 27 patients on EN and 14 on TPN switched from IV infusion insulin to SC insulin. The initial dose of SC insulin was estimated as 50% of the daily IV insulin requirements, extrapolated from the previous 12h. A corrective dose of short-acting insulin (lispro) was used when necessary. ResultsMean blood glucose (BG) level during SC insulin treatment was 136±35mg/dL in the EN group and 157±37mg/dL in the TPN group (p=0.01). In the TPN group, mean BG was >180mg/dL during the first three days after switching, and a 41% increase in the glargine dose was required to achieve the target BG. In the EN group, mean BG remained <180mg/dL throughout the days of transition and the dose of glargine remained unchanged. ConclusionsIn the transition from IV to SC insulin therapy, initial insulin glargine dose estimated as 50% of daily IV insulin requirements is adequate for patients on EN, but inadequate in those given TPN.

Transition from intravenous insulin to subcutaneous long-acting insulin in critical care patients on enteral or parenteral nutrition

Background and aimsThe optimal initial dose of subcutaneous (SC) insulin after intravenous (IV) infusion is controversial, especially in patients receiving continuous enteral nutrition (EN) or total parenteral nutrition (TPN). The aim of this study was to evaluate the strategy used at our hospital intensive care unit (ICU) in patients switched from IV insulin to SC insulin glargine while receiving EN or TPN. Design and methodsA retrospective analysis was made of 27 patients on EN and 14 on TPN switched from IV infusion insulin to SC insulin. The initial dose of SC insulin was estimated as 50% of the daily IV insulin requirements, extrapolated from the previous 12h. A corrective dose of short-acting insulin (lispro) was used when necessary. ResultsMean blood glucose (BG) level during SC insulin treatment was 136±35mg/dL in the EN group and 157±37mg/dL in the TPN group (p=0.01). In the TPN group, mean BG was >180mg/dL during the first three days after switching, and a 41% increase in the glargine dose was required to achieve the target BG. In the EN group, mean BG remained <180mg/dL throughout the days of transition and the dose of glargine remained unchanged. ConclusionsIn the transition from IV to SC insulin therapy, initial insulin glargine dose estimated as 50% of daily IV insulin requirements is adequate for patients on EN, but inadequate in those given TPN.

A suitable palpation technique allows to identify skin lipohypertrophic lesions in insulin-treated people with diabetes.

BackgroundLipohypertrophy (LH) is a major complication of subcutaneous insulin treatment brought about by multiple overlapping injections and/or needle reuse. It is responsible for unacceptable glucose oscillations due to a high rate of hypoglycaemic episodes and rebound glucose spikes. Skin ultrasound scans (USS), the gold standard for its detection, is too expensive for screening purposes.AimsTo define a structured method allowing health professionals (HPs) to identify LH lesions as inexpensively and correctly as possible.MethodsOut of 129 insulin-treated people with diabetes identified by USS as having LH lesions, only 40 agreed to participate in the study (24 females, age 54 ± 15 years, daily insulin dosage 57 ± 12 IU). Each was blindly examined by four well trained and four non-trained HPs according to a standard method involving repeated well codified maneuvers.ResultsA specific training allowed inexperienced HPs to acquire high diagnostic accuracy in identifying LH lesions independent of site, size, shape, and even BMI. This kind of training also allowed to reach a 97 % consistency rate among HPs as compared to USS, while the lack of training was associated with a wide variability and inconsistency of identification results.ConclusionsDiabetes teams should follow systematically the simple procedure reported in this paper for the diagnosis of LH and try to get it further implemented and progressively refined in large scale studies. This would have a major impact on patient education in terms of (1) correct injection technique and (2) ability to identify lesions early enough to prevent poor metabolic outcome.

Effects of intraperitoneal insulin versus subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus.

AimsElevated sex hormone-binding globulin (SHBG) concentrations have been described in patients with type 1 diabetes mellitus (T1DM), probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII), or subcutaneous (SC), influences SHBG concentrations among T1DM patients.MethodsPost hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (±13) years, diabetes duration 23 (±11) years, and hemoglobin A1c (HbA1c) 8.7 (±1.1) (72 (±12) mmol/mol). As secondary outcomes, testosterone, 17-β-estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were analyzed.ResultsEstimated mean change in SHBG was −10.3nmol/L (95% CI: −17.4, −3.2) during CIPII and 3.7nmol/L (95% CI: −12.0, 4.6) during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was −6.6nmol/L (95% CI: −17.5, 4.3); −12.7nmol/L (95% CI: −25.1, −0.4) for males and −1.7nmol/L (95% CI: −24.6, 21.1) for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; −15.8nmol/L (95% CI: −24.2, −7.5) and −8.3nmol/L (95% CI: −14.4, −2.2), respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2U/L (95% CI: 0.1, 2.2) among males.ConclusionsSHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids.

MiRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes.

Background. The use of miRNAs as biomarkers for Type 1 Diabetes (T1D) risk is attractive as T1D is usually diagnosed in front of acute symptoms. As miR-375 is highly expressed in the endocrine pancreas, we postulated that its circulating level might reflect beta cell alterations and might be altered in the blood of T1D patients recently diagnosed. Methods. Sera were obtained from 22 T1D children at onset of the disease, before subcutaneous insulin treatment, and from 10 nondiabetic pediatric controls. MiR-375 seric level was quantified by stem-loop RT-PCR-based assay. MiRNAs regulations in isolated human islets in response to high glucose concentrations were determined by TaqMan Low-Density Array. Results. The abundance of miR-375, among the 410 miRNAs detected in human islets, mirrored its well-established role in rodent islet biology. Upregulated miRNAs targeted genes involved in islet homeostasis and regulation of beta cell mass. Downregulated miRNAs, including miR-375, were involved in pancreas secretion and protein turnover. Seric level of miR-375 was lower in T1D children versus age-matched controls, without any correlations with HbA1c, glycaemia, and number of autoantibodies. Conclusion. Altered circulating level of miR-375 at onset of T1D might be a general biomarker of metabolic alterations and inflammation associated with the disease.

After 6 years of intraperitoneal insulin administration IGF-I concentrations in T1DM patients are at low-normal level

ObjectiveLow concentrations of insulin-like growth factor-I (IGFI) have been reported in type 1 diabetes mellitus (T1DM), suggested to be due to low insulin concentrations in the portal vein. The aim was to describe the long-term course of IGFI concentrations among T1DM subjects treated with continuous intraperitoneal (IP) insulin infusion (CIPII). DesignNineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) insulin therapy in 2006 were followed until 2012. IGF-I measurements were performed at the start of the 2006 study, after the 6month SC- and CIPII treatment phase in 2006 and during CIPII therapy in 2012. Z-scores were calculated to compare the IGF-I concentrations with age-specific normative range values of a non-DM reference population. ResultsIn 2012, IGF-I Z-scores (−0.7; 95% confidence interval −1.3, −0.2) were significantly higher than at the start of the 2006 study (−2.5; −3.3, −1.8), the end of the SC (−2.0; −2.6, −1.5) and CIPII (−1.6; −2.1, −1.0) treatment phase with a mean difference of: 1.8 (0.9, 2.7), 1.3 (0.5, 2.1) and 0.8 (0.1, 1.6), respectively. ConclusionAfter 6years of treatment with CIPII, IGF-I concentrations among T1DM patients increased to a level that is higher than during prior SC insulin treatment and is in the lower normal range compared to a non-DM reference population. The results of this study suggest that long-term IP insulin administration influences the IGF system in T1DM.

Implementation of subcutaneous insulin protocol for non-critically ill hospitalized patients in Andalusian tertiary care hospitals

Abstract Introduction In 2009, the Andalusian Society of Endocrinology and Nutrition designed a protocol for subcutaneous insulin treatment in hospitalized non-critically ill patients (HIP). Objective To analyze implementation of HIP at tertiary care hospitals from the Andalusian Public Health System. Method A descriptive, multicenter study conducted in 8 tertiary care hospitals on a random sample of non-critically ill patients with diabetes/hyperglycemia (n = 306) hospitalized for ≥48 h in 5 non-surgical (SM) and 2 surgical (SQ) departments. Type 1 and other specific types of diabetes, pregnancy and nutritional support were exclusion criteria. Results 288 patients were included for analysis (62.5% males; 70.3 ± 10.3 years; 71.5% SM, 28.5% SQ). A scheduled subcutaneous insulin regimen based on basal-bolus-correction protocol was started in 55.9% (95%CI: 50.5–61.2%) of patients, 63.1% SM vs 37.8% SQ (p Conclusions Strategies are needed to improve implementation of the inpatient subcutaneous insulin protocol, particularly in surgical departments. Sliding scale insulin is still the most common alternative to insulin regimen based on basal-bolus-correction scheduled insulin. Metabolic control assessment during hospitalization should be encouraged.

Effectiveness of a nurse-managed protocol to prevent hypoglycemia in hospitalized patients with diabetes.

Background. Hypoglycemia due to inadequate carbohydrate intake is a frequent complication of insulin treatment of diabetic in-patients. Objective. To assess the effectiveness of a nurse-managed protocol to prevent hypoglycemia during subcutaneous insulin treatment. Design. Prospective pre-post-intervention study. Methods. In 350 consecutive diabetic in-patients the incidence of hypoglycemia (blood glucose < 70 mg/dL) during subcutaneous insulin treatment was assessed before (phase A) and after (phase B) the protocol was adopted to permit (1) the patient to opt for substitutive food to integrate incomplete carbohydrate intake in the meal; (2) in case of lack of appetite or repeatedly partial intake of the planned food, prandial insulin administered at the end of the meal to be related to the actual amount of carbohydrates eaten; (3) intravenous infusion of glucose during prolonged fasting. Results. Eighty-four patients in phase A and 266 in phase B received subcutaneous insulin for median periods of, respectively, 7 (Q1–Q3 6–12) and 6 days (Q1–Q3 4–9). Hypoglycemic events declined significantly from 0.34 ± 0.33 per day in phase A to 0.19 ± 0.30 in phase B (P > 0.001). Conclusions. A nurse-managed protocol focusing on carbohydrate intake reduced the incidence of hypoglycemia in patients with diabetes receiving subcutaneous insulin in hospital.

Implementación del protocolo hospitalario de insulinización subcutánea para pacientes no críticos en hospitales andaluces de tercer nivel

IntroductionIn 2009, the Andalusian Society of Endocrinology and Nutrition designed a protocol for subcutaneous insulin treatment in hospitalized non-critically ill patients (HIP). ObjectiveTo analyze implementation of HIP at tertiary care hospitals from the Andalusian Public Health System. MethodA descriptive, multicenter study conducted in 8 tertiary care hospitals on a random sample of non-critically ill patients with diabetes/hyperglycemia (n=306) hospitalized for ≥48hours in 5 non-surgical (SM) and 2 surgical (SQ) departments. Type 1 and other specific types of diabetes, pregnancy and nutritional support were exclusion criteria. Results288 patients were included for analysis (62.5% males; 70.3±10.3 years; 71.5% SM, 28.5% SQ). A scheduled subcutaneous insulin regimen based on basal-bolus-correction protocol was started in 55.9% (95%CI: 50.5-61.2%) of patients, 63.1% SM vs. 37.8% SQ (P<.05). Alternatives to insulin regimen based on basal-bolus-correction included sliding scale insulin (43.7%), diet (31.3%), oral antidiabetic drugs (17.2%), premixed insulin (1.6%), and others (6.2%). For patients previously on oral antidiabetic drugs, in-hospital insulin dose was 0.32±0.1IU/kg/day. In patients previously on insulin, in-hospital insulin dose was increased by 17% [-13-53], and in those on insulin plus oral antidiabetic drugs, in-hospital insulin dose was increased by 26.4% [-6-100]. Supplemental insulin doses used for<40IU/day and 40-80IU/day were 72.2% and 56.7% respectively. HbA1c was measured in 23.6% of patients (95CI%: 18.8-28.8); 27.7% SM vs. 13.3% SQ (P<.05). ConclusionsStrategies are needed to improve implementation of the inpatient subcutaneous insulin protocol, particularly in surgical departments. Sliding scale insulin is still the most common alternative to insulin regimen based on basal-bolus-correction scheduled insulin. Metabolic control assessment during hospitalization should be encouraged.

Report of a 7 year case–control study of continuous intraperitoneal insulin infusion and subcutaneous insulin therapy among patients with poorly controlled type 1 diabetes mellitus: Favourable effects on hypoglycaemic episodes

AimsContinuous intraperitoneal insulin infusion (CIPII) is a last-resort treatment option for patients with type 1 diabetes mellitus (T1DM) who fail to reach adequate glycaemic control with subcutaneous (SC) insulin therapy. Aim was to compare the long-term effects of CIPII and SC insulin therapy among patients with T1DM in poor glycaemic control. MethodsPatients in which CIPII was initiated in 2006 were compared with a control group of T1DM patients who continued SC therapy. Linear mixed models were used to calculate differences between the baseline (2006) and final (2013) measurements within and between groups. ResultsA total of 95 patients of which 21 were using CIPII and 74 using SC insulin were included. Within the CIPII group, the number of hypoglycaemic episodes decreased with −5 (95% CI −8 to −3) per 2 weeks while it remained stable among SC patients. Over time, only the number of hypoglycaemic episodes decreased more with CIPII as compared to SC insulin treatment (difference: −6 (95% CI −9 to −4)). There were no differences between treatment groups regarding clinical parameters and quality of life scores over time. Pump or catheter dysfunction led to ketoacidosis in 6 patients: 2 using CIPII and 4 SC insulin. ConclusionsAfter 7 years of follow-up, there is a persistent decline of hypoglycaemic events among CIPII treated T1DM patients. Besides less hypoglycaemic episodes with CIPII therapy, there are no differences between long-term CIPII and SC insulin therapy.

Systematic review: continuous intraperitoneal insulin infusion with implantable insulin pumps for diabetes mellitus

Continuous intraperitoneal insulin infusion (CIPII) with implantable insulin pumps (IIPs) is a treatment option for diabetes, which is not widely utilized nor freely accessible in clinical practice. The aim of this study was to summarize available evidence on use of IIPs for CIPII for diabetes treatment, since its introduction to clinical use on the following outcomes: HbA1c, hypoglycaemic events, and complications of treatment. complications of diabetes and treatment satisfaction. Following the procedure for a systematic review this paper may contribute to a balanced evaluation of the need and effectiveness of IIPs. A pre-specified, registered protocol (CRD42012002150) was followed. Studies investigating all diabetes populations and types of IIPs were considered eligible. The sensitive search strategy was developed in collaboration with a clinical librarian and contents experts. PUBMED, MEDLINE, CENTRAL EMBASE, trial registries, and other databases were searched. References were screened independently by two authors, and decisions on study selection were recorded. Of the 1,703 references screened, 362 were assessed as potentially eligible. Ninety-four were identified as studies using IIPs. Fifteen papers, together reporting on four-randomized trials, and eight cohorts were included. Narrative analysis is provided, and data tables are available. CIPII by way of IIPs is effective in lowering HbA1c levels and reducing hypoglycaemic events. Superiority of IIP treatment is likely related to patient characteristics, one subgroup being patients unable to acquire satisfactory glycaemic control with subcutaneous insulin treatment. Higher treatment satisfaction was also reported for this subgroup. For these patients, risk of morbidity may be considered acceptable. Patients' perspectives, influence on quality of life, and possible other outcomes should also be considered important factors in weighing individual benefits and risks. A more uniform method of reporting would help strengthen the evidence base.

Conventional insulin vs insulin infusion therapy in acute coronary syndrome diabetic patients.

To evaluate the impact on glucose variability (GLUCV) of an nurse-implemented insulin infusion protocol when compared with a conventional insulin treatment during the day-to-day clinical activity. We enrolled 44 type 2 diabetic patients (n = 32 males; n = 12 females) with acute coronary syndrome (ACS) and randomy assigned to standard a subcutaneous insulin treatment (n = 23) or a nurse-implemented continuous intravenous insulin infusion protocol (n = 21). We utilized some parameters of GLUCV representing well-known surrogate markers of prognosis, i.e., glucose standard deviation (SD), the mean daily δ glucose (mean of daily difference between maximum and minimum glucose), and the coefficient of variation (CV) of glucose, expressed as percent glucose (SD)/glucose (mean). At the admission, first fasting blood glucose, pharmacological treatments (insulin and/or anti-diabetic drugs) prior to entering the study and basal glycated hemoglobin (HbA1c) were observed in the two groups treated with subcutaneous or intravenous insulin infusion, respectively. When compared with patients submitted to standard therapy, insulin-infused patients showed both increased first 24-h (median 6.9 mmol/L vs 5.7 mmol/L P < 0.045) and overall hospitalization δ glucose (median 10.9 mmol/L vs 9.3 mmol/L, P < 0.028), with a tendency to a significant increase in first 24-h glycaemic CV (23.1% vs 19.6%, P < 0.053). Severe hypoglycaemia was rare (14.3%), and it was observed only in 3 patients receiving insulin infusion therapy. HbA1c values measured during hospitalization and 3 mo after discharge did not differ in the two groups of treatment. Our pilot data suggest that no real benefit in terms of GLUCV is observed when routinely managing blood glucose by insulin infusion therapy in type 2 diabetic ACS hospitalized patients in respect to conventional insulin treatment.

Difficult Management of Glucose Homeostasis in a 21-Month-Old Child With Type 1 Diabetes and Unknown Glutaric Aciduria Type I: A Case Report

A 21-month-old boy with previously diagnosed type 1 diabetes was admitted to our unit, presenting with glycometabolic failure (pH 7.30; base excess −11.9 mmol/L; blood glucose 17.3 mmol/L; HbA1c 10.4% [90 mmol/mol]; glycosuria; and ketonuria). During physical examination he was dehydrated and pale and presented with axial hypotonia with hyposthenia, poor head control, hypotonic legs, and hyporeflexia. His neurological clinical status became compromised after the diagnosis of type 1 diabetes when he was 15 months old. During hospitalization, the management of blood glucose homeostasis was difficult because of a high level of glycemic variability. Hypo- and hyperglycemic episodes were associated with acute encephalopathic crises characterized by hypotonia, dyskinetic movements, difficulty swallowing, and episodes of opisthotonus with no loss of consciousness. For better control of blood glucose, subcutaneous insulin treatment was …

Short‐term subcutaneous insulin treatment delays but does not prevent diabetes in NOD mice

Despite encouraging results in the NOD mouse, type 1 diabetes prevention trials using subcutaneous insulin have been unsuccessful. To explain these discrepancies, 3-week-old NOD mice were treated for 7 weeks with subcutaneous insulin at two different doses: a high dose (0.5 U/mouse) used in previous mouse studies; and a low dose (0.005 U/mouse) equivalent to that used in human trials. Effects on insulitis and diabetes were monitored along with immune and metabolic modifications. Low-dose insulin did not have any effect on disease incidence. High-dose treatment delayed but did not prevent diabetes, with reduced insulitis reappearing once insulin discontinued. This effect was not associated with significant immune changes in islet infiltrates, either in terms of cell composition or frequency and IFN-γ secretion of islet-reactive CD8(+) T cells recognizing the immunodominant epitopes insulin B(15-23) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)(206-214). Delayed diabetes and insulitis were associated with lower blood glucose and endogenous C-peptide levels, which rapidly returned to normal upon treatment discontinuation. In conclusion, high- but not low-dose prophylactic insulin treatment delays diabetes onset and is associated with metabolic changes suggestive of β-cell "rest" which do not persist beyond treatment. These findings have important implications for designing insulin-based prevention trials.