Injections Of Regular Insulin Research Articles

Innovative cell transplant advancement A Research breakthrough by Chinese doctors for diabetes management

This study presents a groundbreaking advancement in diabetes treatment achieved by Chinese scientists through an innovative cell transplant technique. Traditional diabetes management, typically involving regular insulin injections and constant monitoring, imposes a significant burden on patients. However, this new therapy promises to revolutionize diabetes care. A team of researchers from Shanghai Changzheng Hospital, the Centre for Excellence in Molecular Cell Science under the Chinese Academy of Sciences, and Renji Hospital successfully cured a 59-year-old patient with type-2 diabetes using cell therapy. The patient, whose blood sugar levels remained uncontrolled despite regular insulin injections, underwent a cell transplant in July 2021. Peripheral blood mononuclear cells from the patient were reprogrammed into "seed cells" that act like pancreatic islet cells and then implanted. Within eleven weeks, the patient no longer required insulin injections, and after a year, he stopped all diabetes-related medications. Follow-up examinations confirmed the restoration of pancreatic islet function, and the patient has been insulin-free for 33 months, highlighting the long-term efficacy of the treatment. This therapy harnesses the body's regenerative capabilities, marking a significant milestone in regenerative medicine. The innovative approach not only cures the patient but also offers the potential for preventing diabetes. With China facing a substantial healthcare burden due to its high diabetes prevalence, this technique could significantly alleviate the burden by reducing dependency on lifelong insulin injections.

Description of knowledge, attitudes and practices to maintain oral hygiene as well as gingival index and plaque index in children suffering from type 1 diabetes mellitus

Background: Diabetes mellitus is a chronic disease whose incidence continues to increase throughout the world. Periodontal disease is a complication of diabetes. Poor periodontal health can lead to a variety of serious health problems. Therefore, this research is considered important to determine knowledge, attitudes and practices to maintain oral hygiene as well as gingival index and plaque index in children with type 1 diabetes mellitus. Objectives: To determine the description of knowledge, attitudes and practices to maintain oral hygiene as well as gingival index and plaque index in children with type 1 diabetes mellitus. Method: This research is a cross-sectional observational analytical study consisting of 32 respondents from children suffering from T1DM and members of IKADAR Malang. The instrument used was a questionnaire to measure knowledge, attitudes and practices regarding cleaning teeth and mouth; insulin injection compliance, diet, and physical activity. Hba1c to determine DMT-1 status. Gingival and plaque index. Results and discussions: Respondents with controlled diabetes, good knowledge, attitudes and practices all had healthy gingiva and good PI, namely 3 (15.79%). respondents with regular insulin, good diet and low physical activity all had uncontrolled diabetes, namely 2 (7.14%). Conclusion: The majority of respondents have uncontrolled diabetes, knowledge, attitudes, practices to maintain good oral hygiene, healthy gingiva, and good PI in one unit, namely 9. The majority of respondents have regular insulin injection compliance, moderate diet, low physical activity, and uncontrolled diabetes mellitus status in one unit, namely 17.

A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.

Type 1 Diabetes (T1D) is a chronic autoimmune disease characterized by a gradual destruction of insulin-producing β-cells in the endocrine pancreas due to innate and specific immune responses, leading to impaired glucose homeostasis. T1D patients usually require regular insulin injections after meals to maintain normal serum glucose levels. In severe cases, pancreas or Langerhans islet transplantation can assist in reaching a sufficient β-mass to normalize glucose homeostasis. The latter procedure is limited because of low donor availability, high islet loss, and immune rejection. There is still a need to develop new technologies to improve islet survival and implantation and to keep the islets functional. Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells with high plasticity that can support human pancreatic islet function both in vitro and in vivo and islet co-transplantation with MSCs is more effective than islet transplantation alone in attenuating diabetes progression. The beneficial effect of MSCs on islet function is due to a combined effect on angiogenesis, suppression of immune responses, and secretion of growth factors essential for islet survival and function. In this review, various aspects of MSCs related to islet function and diabetes are described.

921-P: Improved Glycemic Control in Pregnancy Using Continuous Subcutaneous Infusion of Concentrated Insulin

Maternal and fetal complications are high in preexisting uncontrolled type 2 diabetes mellitus (T2DM). There is limited data on the use of concentrated insulin in continuous subcutaneous insulin infusion (CSII) during pregnancy. We report a case of 22-year-old woman G4P0030 with T2DM since 10 years of age who was admitted for preterm premature rupture of membrane at 26 weeks gestation. Preconception HbA1c was 12.1% on metformin, and basal bolus insulin. Severe hyperglycemia following betamethasone administration for fetal lung maturity required insulin drip initially which was transitioned to basal bolus insulin. Despite total daily insulin dose >480 units, glucose control was suboptimal. Decision was made to initiate CSII with basal U-500 concentrated regular insulin and U-100 prandial insulin injections. She was started on Dexcom for CGM and Omnipod Dash with basal rate 1.3 units/hour (6.5 units/hour U-500), insulin sensitivity factor 27 mg/dl (5.4 mg/dl with U-500), carb ratio 1 unit lispro to 2 g. Glycemic control improved as noted in CGM even after adjusting the pregnancy target (70-140mg/dl). Patient delivered a male infant (2090 grams) by emergency C-section at 30 weeks gestation due to preterm labor with fetal malpresentation. She was discharged home with U-100 basal bolus insulin regimen on day 3 postpartum. Concentrated insulin in CSII is effective for uncontrolled T2DM in pregnancy. Disclosure N.Mon: None. S.Krishnasamy: None.

ISPAD Clinical Practice Consensus Guidelines 2022: Ramadan and other religious fasting by young people with diabetes.

ISPAD Clinical Practice Consensus Guidelines 2022: Ramadan and other religious fasting by young people with diabetes.

Evaluation of the Anti-Diabetic Potential of Probiotic Lactobacillus fermentum (PRI 29) Isolated from Cameroonian Fermented Cow Milk in Alloxan Induced Diabetes Type-1 Mice Model

Background: Diabetes remains a global public health concern in the world. Much is known about the burden of type 2 diabetes as opposed to type 1 diabetes mellitus (T1DM) hence underdiagnosis is evident. Diabetes type 1 is often associated with multiple symptoms and patients with type 1 diabetes are left with regular insulin injection as remedy despite odds of the fact that it is sprout by multiple challenges ranging from hypoglycemia, expensive nature and inconveniences. The use of probiotic bacteria appears today as one of safer alternative to alleviate diabetes and symptoms. Aim of the study: This study aims at characterizing potential hypoglycemic probiotic lactic acid bacterium from fermented cow milk and to evaluate its effects on anthropometric parameters of type-1 diabetes mellitus (T1DM) in an alloxan-induced mice model. Methods: The lactic acid bacteria were isolated from samples of Fulani cow milk using pour plating technique on de Man Rogosa and Sharpe (MRS) agar. The isolates were then further characterized phenotypically and molecularly using the 16s rRNA gene sequencing. Type-1 diabetes mellitus was induced in Balb-c mice by administration of 150mg/Kg B.w of alloxan intraperitoneally, twice consecutively. Animals were randomly divided into 6 groups after induction with 150mg/kg of alloxan per body weight except Group I (normal control). Animals were treated with different probiotic doses of concentration: 9x108 CFU/mL, 1.8x109 CFU/mL and 2.7x109CFU/mL respectively and insulin as positive control. MDA, NO levels as well as anti-oxidant levels (SOD, CAT, GSH) were measured from pancreatic homogenate. Results: One isolate (PRI 29) was selected based on its functional properties like resistance to simulated gastro-intestinal stress environment (acid and bile salt tolerance) and absence of hemolytic activity. This probiotic isolate was identified as a strain of Lactobacillus fermentum. The isolate was sensitive to 10 tested antibiotics including vancomycin, Imipenem and Ciprofloxacin. The isolate resisted acid and bile salts since there was no significant difference (p >0.05) between viable count before and after incubation pH 2.5 and bile salts concentration of 0.3 and 0.6%. Administration of probiotic LAB significantly (p<0.001) ameliorated polydipsia and polyphagia. The glucose and oral glucose tolerance levels were ameliorated in probiotics treated groups p<0.05 as compared to the untreated group. Administration of Lactobacillus fermentum strain was capable of significantly ameliorating oxidative stress in LAB treated mice compared to untreated group (p<0.001) demonstrated by decrease in pro-oxidant NO and MDA. The administration of probiotics led to increase in anti-oxidants (SOD, GSH & CAT) to scavenge oxidative stress biomarkers within the mice treated group (p<0.05). Conclusion: The selected Probiotic lactic acid bacterium isolated from cow milk possess antidiabetic and anti -oxidant properties.

Antidiabetic effects of Psidium x durbanensis Baijnath & Ramcharun ined. (Myrtaceae) leaf extract on streptozotocin-induced diabetes in rats

Ethnopharmacological relevancePsidium guajava L. leaves are used to treat diabetes in South African folkloric medicine and in other parts of the world. Psidium x durbanensis Baijnath & Ramcharun ined. (PD) is a natural sterile hybrid and congener of Psidium guajava that is expected to share the medicinal properties of the genus Psidium and is widely distributed in South Africa.Aim of the study: This study investigates the antioxidant, antidiabetic effects, and mechanisms of action of hydro-methanolic leaf extracts of PD on streptozotocin-induced diabetes in rats. Material and methodsPhytochemical constituents of hydro-methanolic extract of PD were analyzed by gas chromatography-mass spectrometry (GC-MS). Male Wistar rats 250–300 g body weight (BW) were rendered diabetic after a single intraperitoneal injection with streptozotocin, 45 mg/kg BW. The diabetic rats were treated with hydro-methanolic (20:80 v/v) leaf extracts of PD (400 mg/kg/BW) or subcutaneous injections of regular insulin (2.0U/kg/BW, bid) for 56 days. The body weights of the animals were recorded daily. Fasting blood glucose, glucose tolerance tests, and insulin resistance index were measured. The effects of the extracts on total superoxide dismutase, catalase, and reduced glutathione activities, histopathology, and gene expression of insulin receptor substrate 1 and glucose transporter 4 were determined in the liver, pancreas, and gastrocnemius muscles of the rats. ResultsIn the acute toxicity studies, there were no signs of toxicity observed for PD up to 2000 mg/kg BW doses. Diabetic animals showed significant weight loss, elevated and reduced fasting blood glucose and insulin, respectively, impaired glucose tolerance and diminished antioxidant enzymes’ activities compared to controls. Treatment with PD hydro-methanolic leaf extracts improved body weight, glucose tolerance, insulin resistance, and antioxidant enzymes but not plasma insulin in diabetic animals compared to controls, respectively. GC-MS analysis identified organic acids, alcohols, vitamins, terpenoids, and esters in the extracts. Treatment with PD improved glucose uptake by stimulating mRNA expression of GLUT 4 in gastrocnemius muscles of diabetic animals compared to the untreated control and also restored histological aberrations in the pancreas and liver of diabetic rats compared with the untreated control rats. ConclusionCollectively, the present study suggests that treatment with PD leaf extracts significantly ameliorated diabetes symptoms and oxidative stress in rats, and these effects may be linked to the bioactive phytoconstituents present in the plant. This study further suggests that PD improves insulin resistance by increasing glucose uptake in gastrocnemius muscles in an insulin-independent manner.

Information (Digital) Rights of Children, Illegally Displaced from the Ukrainian Territory During Wartime: Mechanisms of International Legal Protection

This scientific publication is designed to prove that mechanisms of child protection in armed conflicts established by international legal instruments as well as local regulations and investigated in this paper are not sufficient to sustain the Russian aggression. It is necessary to introduce new stringent standards as an immediate and effective response from the international community to the abduction of every child. Children in the occupied territories have the right to always communicate with their parents, receive psychological and medical help. In all circumstances, children have the right to liberty and security of person, the right to know their origins, keep their personal documents and receive education in their mother tongue. The main objective of this scientific publication is to research the international legal experience on protection of information (digital) rights of children unlawfully removed from the territory of their residence during wartime or living in the occupied territories as well as to suggest improvements to the current legislation. The authors conclude that to reach the adequate level of protection of information (digital) rights of children illegally removed from the Ukrainian territory during the war or living in the occupied territories, the global transformation of legislation is necessary, primarily in terms of inclusive protection of children, effective prevention of violence and practical involvement of children in peace processes. We recommend fundamentally revising the personal data protection of children surviving in hostile environment, taken into captivity or living on the occupied territories. International legal instruments adopted within the subsequent institutional reforms should not only establish declarative statements, but also penalties for violation of the humanitarian law. Further steps are: establishment of the database on children living in the military action zones and on children taken as prisoners or living in the occupied territories; ensure the unimpeded access of parents to this database; provide means of contact between children and parents, including mobile connection. It is also necessary to ensure the right of children in captivity or under occupation to communication and education in their mother tongue; to prevent adoption of captured children or children residing in occupied territories according to simplified procedure and to prohibit the use of children as means of exchange. Moreover, it is vital to ensure the accountability of war criminals, prohibit the use of child labor and involvement of children in hostilities, prohibit the use of children as human shields, provide children with psychological and medical help and prohibit any forms of discrimination against children or persons with special needs that are held captive or live under occupation. Children and persons who need regular insulin injections, dialysis, radiation or chemotherapy should be provided with the adequate medical care.

One hundred years after the discovery of insulin: a new revolution for patients living with type 1 diabetes?

The year 2021 saw the 100-year celebration of the discovery of insulin as a treatment for type 1 diabetes, saving lives of people previously condemned by the disease. However, insulin replacement, so different from physiological secretion, remains a challenge. Until the 1990s, people living with type 1 diabetes were treated with two injections of intermediate insulin and prandial regular insulin injections. Their kinetics led to frequent hypoglycemia, justifying meals taken at fixed times, with fixed amount of carbohydrates avoiding fast sugars. The development of rapid and then long acting insulin analogues in the 1990s and 2000s and the principle of patient empowerment have reduced these constraints by introducing the notion of functional insulin therapy, dissociating meals managed by rapid insulins from basal insulin (= insulin for living). Meals can be taken at variable times, with variable carbohydrate content and without food restrictions. But the revolution started 5 years ago, with the development of continuous glucose monitoring systems, freeing the patient from blood glucose controls, coupled thereafter to an insulin pump driven by artificial intelligence in the very recent hybrid closed-loop systems. These systems showed significant glucose control improvement, together with reduction of both the time spent in hypoglycemia and the mental burden on the individual, pending a cure for the disease for the next century.

A Phase 2 Evaluation of a Novel Co-Formulation of Pramlintide and Regular Insulin to Improve Postprandial Glycemic Control in Adults with Type 1 Diabetes (T1D)

Objective: Pramlintide co-administration, used in conjunction with prandial insulin, has substantial clinical benefits to improve post-prandial glucose excursions, glycemic variability (GV) and time in range (TIR), but is associated with an increased injection burden that adversely affects adherence and persistence. A novel, fixed-ratio co-formulation of pramlintide and regular insulin (XP-3924) was evaluated in a phase 2 single injection study measuring XP-3924 pharmacokinetics (PK), glucose pharmacodynamics (PD), and its effects upon overall glycemic control. Methods: This was a Phase 2 randomized, open-label, active comparator-controlled, three-period cross-over study, which enrolled 18 adults with T1D to compare the PK and PD, glycemic affects and safety and tolerability of a single dose of XP-3924, to co-administration of regular insulin (Humulin® R) and pramlintide (Symlin®), and to an injection of regular insulin (RI) alone. Subjects were randomly allocated to a sequence of three treatments: XP-3924 (with 50% insulin reduction based their insulin to carbohydrate ratio), RI, or co-administration (RI with 50% insulin reduction plus a comparable pramlintide dose, co-administered as separate injections). The study drugs were administered subcutaneously 30 minutes before a 75-gram oral glucose challenge and glucose levels were monitored for 6 hours. Results: XP-3924 treatment resulted in a 62.3% reduction of hyperglycemia (blood glucose AUC0-3 hr >180 mg/dL) after the glucose challenge when compared to RI (p<0.001), and exhibited comparable postprandial glycemic control to that of the co-administration. After the oral glucose challenge, the mean absolute change in blood glucose and was less in XP-3924 when compared to both co-administration and to RI (197.7±70.74 mg/dL, 230.5±162.39 mg/dL, 254.2±195.21 mg/dL, respectively), as well as GV as defined by the comparison of the intrasubject coefficient of variation of plasma glucose readings across study treatments (53.3%, 62.1%, 71.0%, respectively). The PK of Pramlintide in XP-3924 when compared to co-administration, exhibited longer median Tmax [40.5 (range 21.0–150.0) minutes versus 10.0 (range 10.0–24.0) minutes, respectively], and comparable AUC0-360. The incidence and severity of treatment emergent adverse events (e.g., injection site reactions, minimal nausea and vomiting) was comparable across all treatment arms with no drug-related serious adverse events. Conclusion: XP-3924 was well tolerated and significantly improved post-prandial glucose excursions and glycemic variability compared to regular insulin. XP-3924 also exhibited a favorable PK and PD profile and may be a viable alternative to insulin and pramlintide co-administration to improve treatment adherence and overall glycemic control, especially after meals, addressing an unmet need in the clinical care of people with type 1 diabetes.

New approach to deep diabetic foot ulcer (DFU) treatment-potential of secretome from Wharton’s jelly mesenchymal stem cell therapy

Diabetic foot ulcer is one of the complications of chronic diabetes in the form of lesions in deep tissue and associated neurological disorders and peripheral vascular disease in the lower limbs. DFU has a significant impact on the health and quality of life of patients and their families. The effect that is often felt is ranging from pain, loss of function and mobility, depression, difficulty and anxiety, shame, social isolation, the financial burden of extended hospital stays and chronic morbidity, or even amputation to death. This case report reports the case of a 64-year-old man with DFU grade 3 and has been advised to undergo a finger amputation surgery by a surgeon to prevent infection, and the finger is predicted to be untenable. After intervention with a single dose, intracutaneous injection of Secretome from-Placental Wharton Jelly Stem Cell (SC-PWJSC), regular insulin, and control Sugar Blood Glucose. There is a very significant wound repair. Patients reported being satisfied with this treatment.

2205-PUB: New Strategy for Treating Diabetes with Traditional Chinese Medicine

Introduction: Diabetes is a group of metabolic disorders characterized by high blood glucose in patients. In spite of numerous progresses have been achieved in diabetes research and care, it is still challenging to cure diabetes. The objective of this study was to explore a new approach to treat diabetes with Traditional Chinese Medicine. Materials and Method: The Traditional Chinese Medicine used in this study was a natural bio-product(s) (NBP) which has been used for humans for several hundred years. This NBP was dried and grinded into powders and capsulated (patent pending). Based on the degree of severity determined by OGTT data analysis, patients took 4.5g - 30g of this NBP orally per day for 3 to 24 months, and might take prescribed medicines (Gliclazide MR, Metformin, and/or Saxagliptin) at the initial stage of therapy. Starting on the first day of therapy, the patients discontinued the insulin injection if they had relied on it. Results: The patients ranged from 34 yo to 73 yo (mean=55.6 yo, n=18). Before therapy, six of 18 patients were on a regular insulin injection with various dosages, and the mean HbA1c was 7.65 (SD=1.97, n=18). After therapy (without any insulin injection) for an average of 231 days (97-748 days), the mean HbA1c was 6.61 (SD=0.86, n=18). The difference was statistically different (t-test, p=0.008). Ten of 18 patients were on western medicines for an average of 77 days while the rest took NBP only. The insulin resistance (estimated by HOMA-IR) decreased and the disposition index (estimated at 2-h OGTT) increased in 12 of the 18 patients. Discussion and Conclusion: This NBP can effectively control plasma glucose level by reducing the insulin resistance and enhancing the beta cell functions. However, its exact mechanism is not clear, partially because this NBP is a compound which may affect multiple systems simultaneously. This method might not be suitable for all patients with T2DM. Further studies are needed in order to fully understand its mechanisms for controlling plasma glucose level. Disclosure X. Hua: Board Member; Self; CYX Biotechnology Ltd. A.Y. Huang: Research Support; Self; CYX Biotechnology Co.

An Intelligent Nanoscale Insulin Delivery System.

Insulin injection relies on strict blood glucose monitoring. However, existing techniques and algorithms for blood glucose monitoring cannot be completed in a timely way. In this study, we have developed a new intelligent glucose-sensitive insulin delivery system to stabilize blood glucose levels in the body. This system does not require real-time detection of blood glucose. First, we successfully synthesized a nanoscale material called PAM-PAspPBA-b-PEG by using chemical methods. We then conducted TEM, DLS, and 1H-NMR analyses to characterize the physicochemical properties, such as size, molecular composition, and configuration of the nanomaterial. We verified the glucose responsibility of the insulin loading nanoscale material in vitro and evaluated its safety and effect on mice in vivo. Results showed that insulin-loaded PAM-PAspPBA-b-PEG is glucose-sensitive, safer and more effective than regular insulin injection. This study provides a basis for future development of smart insulin delivery systems.

Oral lactate intensifies insulin toxicity during severe insulin-induced hypoglycemia in mice

ABSTRACT We investigated whether oral lactate could prevent seizures and deaths in mice with severe hypoglycemia induced by a high dose of insulin. For this purpose, mice were fasted for 15 h and then given an intraperitoneal injection of regular insulin (5.0 U/kg or 10.0 U/kg). Immediately after insulin injection, the mice received an oral dose of saline (control), glucose (5.5 mmol/kg), or lactate (18.0 mmol/kg). Glucose and lactate levels were measured in the blood and brain before and after the seizures began. Glucose and lactate delayed (p < 0.05) the onset of seizures associated with severe insulin-induced hypoglycemia. Elevated (p < 0.05) brain levels of lactate were associated with an absence of seizures in mice that received glucose or lactate, suggesting that lactate could prevent convulsions associated with severe insulin-induced hypoglycemia. However, the same oral dose of lactate that delayed the onset of convulsions also increased the mortality rate. In contrast, diazepam (3.0 mg/kg) prevented seizures and markedly decreased the frequency of death during severe insulin-induced hypoglycemia. The results demonstrated that in contrast to oral glucose, oral lactate intensifies insulin toxicity.

Acetylcholine precursor, citicoline (cytidine 5'-diphosphocholine), reduces hypoglycaemia-induced neuronal death in rats.

Citicoline (cytidine 5'-diphosphocholine) is an important precursor for the synthesis of neuronal plasma membrane phospholipids, mainly phosphatidylcholine. The administration of citicoline serves as a choline donor for the synthesis of acetylcholine. Citicoline has been shown to reduce the neuronal injury in animal models with cerebral ischaemia and in clinical trials of stroke patients. Citicoline is currently being investigated in a multicentre clinical trial. However, citicoline has not yet been examined the context of hypoglycaemia-induced neuronal death. To clarify the therapeutic impact of citicoline in hypoglycaemia-induced neuronal death, we used a rat model with insulin-induced hypoglycaemia. Acute hypoglycaemia was induced by i.p. injection of regular insulin (10Ukg-1 ) after overnight fasting, after which iso-electricity was maintained for 30minutes. Citicoline injections (500mg/kg, i.p.) were started immediately after glucose reperfusion. We found that post-treatment of citicoline resulted in significantly reduced neuronal death, oxidative injury and microglial activation in the hippocampus compared to vehicle-treated control groups at 7days after induced hypoglycaemia. Citicoline administration after hypoglycaemia decreased immunoglobulin leakage via blood-brain barrier disruption in the hippocampus compared to the vehicle group. Citicoline increased choline acetyltransferase expression for phosphatidylcholine synthesis after hypoglycaemia. Altogether, the present findings suggest that neuronal membrane stabilisation by citicoline administration can save neurones from the degeneration process after hypoglycaemia, as seen in several studies of ischaemia. Therefore, the results suggest that citicoline may have therapeutic potential to reduce hypoglycaemia-induced neuronal death.

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.

Clinical study on local application of low-dose insulin for promoting wound healing after operation for deep burns.

Transplanted free skin flaps are often needed to treat deep burns; their survival, however, is less than optimal. This study examined whether local low-dose insulin injections can promote flap survival and wound healing after surgery. A total of 165 patients who underwent free skin flap transplantation for simple deep burns were enrolled in the study and divided into 5 groups of 33 patients each: Blank control group (no local subcutaneous drug injections), saline control group (saline injections), low-dose insulin group (0.5 units regular insulin injections), medium-dose group (1.0 units regular insulin injections) and high-dose group (2.0 units regular insulin injections). Wound healing and flap survival conditions were assessed and compared among groups. The best wound healing rate found was that of the low-dose insulin injection group where all the parameters measured improved significantly: The healing time was shorter; the blood flow volume, the flap survival, the number of fibroblasts and new vessels increased; the re-epithelialization occurred faster; the infiltration of inflammatory cells was reduced; the expression levels of heat shock protein-90, vascular endothelial growth factor, transforming growth factor-β and interleukin-1 were higher; and the plasma glucose levels only fluctuated slightly. The results clearly demonstrate that a local low-dose insulin regime after flap transplantation can accelerate the healing time and improve the surgical outcome without exerting detrimental secondary effects on the glucose plasma level of deep burn patients.

Evaluation of an Insulin Sensitivity Index from the Short Intravenous Glucose Tolerance Test

The aim of this analysis was to compare insulin sensitivity indices calculated from a short (50 min), insulin‐modified intravenous glucose tolerance test (IVGTT; Tura SI) to that from a full 180 min IVGTT using minimal model analysis (MM SI), as well as the Matsuda Index (M‐SI) from a 120 min liquid meal tolerance test (Maki et al. Diabetes Tech Ther 2011;13:661–6). The IVGTT included glucose (0.3 g/kg, t = 0 min) and regular human insulin (0.03 U/kg; t = 20 min) injection with samples collected at frequent intervals over 180 min. Tura SI was calculated as the fractional glucose disappearance rate/average increment in plasma insulin, both from 10–50 min. The MINMOD MILLENNIUM program (v6.02) was used to calculate MM SI. Subjects were overweight or obese men (n = 8) and women (n = 16) without diabetes who agreed to participate in a substudy after completing a dietary intervention trial. Mean ± SEM MM SI was 3.94 ± 3.38 × 10−4 L*min−1*mU−1, age was 48.9 ± 2.0 y and body mass index was 30.8 ± 0.6 kg/m2. Pearson correlation coefficients were: Tura SI with MM SI r = 0.963, Tura SI with M‐SI r = 0.803, and MM SI with M‐SI r = 0.776, all p &lt; 0.001. Thus, Tura SI from the first 50 min of an insulin‐modified IVGTT correlates very strongly with 180 min MM SI (reference method), and the relationship between Tura SI with M‐SI was similar in magnitude to that between MM SI and M‐SI. These results suggest that the short IVGTT may be used as a less costly and time‐consuming alternative to the 180 min IVGTT for assessment of whole‐body insulin sensitivity.Support or Funding InformationIngredion, Westchester, IL

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.

Characterization of stability and inflammatory response to alginate encapsulated islets in the omentum pouch model

Characterization of stability and inflammatory response to alginate encapsulated islets in the omentum pouch model