NPH Insulin Research Articles

Safety and efficacy of insulin detemir vs. insulin NPH in pregnant women with diabetes: a systematic review and meta-analysis.

The relative efficacy and safety of insulin neutral protamine Hagedorn (NPH) and detemir (IDet), in the management of diabetes in pregnancy remains unclear. We sought to conduct an updated systematic review and meta-analysis to study the effect of NPH versus IDet during pregnancy on clinically relevant maternal and fetal outcomes. MEDLINE and Google Scholar were queried from inception till September 2022 for original studies comparing NPH with IDet for management of diabetes during pregnancy. Data was pooled using a random-effects model, to generate risk ratios (RR) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes, along with 95% confidence intervals (CIs). I2 test was used to assess the magnitude of heterogeneity. Sensitivity analysis was conducted to explore the potential source of heterogeneity. As less than ten studies were included in our analysis, funnel plots were not made to evaluate publication bias. A P value of ≤0.05 was considered significant in all cases. Our search of the literature yielded 1087 articles initially, of which seven articles comprising 1396 patients, were included in our analysis. All included articles were of reasonably high methodological quality. Our pooled analysis demonstrates no statistically significant difference between the efficacy of insulin Detemir and insulin NPH as assessed by the HbA1c values from baseline. For safety outcomes, insulin detemir was significantly associated with a greater gestational age at delivery (WMD=0.39, 95%CI: 0.07 to 0.71, P=0.02) and lower incidence of hypoglycemic events (RR=0.64, 95%CI: 0.48 to 0.86, P=0.003) in-contrast to insulin NPH. Our findings demonstrate that both, insulin IDet and insulin NPH have a similar efficacy in reducing HbA1c from baseline. However, insulin detemir was associated with lesser incidence of maternal hypoglycemic events and greater gestational age at delivery, compared to NPH.

Clinical Evidence and Practice-Based Guidelines on the Utility of Basal Insulin Combined Oral Therapy (Metformin and Glimepiride) in the Current Era.

Basal insulin combined oral therapy consisting of insulin and oral anti-diabetic drugs (OADs) is recommended for type 2 diabetes uncontrolled on OADs. There is a lack of clear evidence and recommendations on the combined use of basal insulin analogues to more than one OADs (glimepiride plus metformin) in effective control of glycemic parameters and its safety in terms of reduced hypoglycemic events, weight gain and cardiovascular risk. In this context, a group of clinical experts discussed the utility of basal insulin combined oral therapy with metformin and glimepiride in the current era. The clinical experts discussed and provided their inputs virtually. The expert panel included clinical experts comprising endocrinologists and diabetologists from India and Nepal. The panel thoroughly reviewed existing literature on the subject and proposed clinical evidence and practice-based guidelines. These current clinical practice guidelines highlight the efficacy and safety of basal insulin combination therapy with various available basal insulins including neutral protamine hagedorn, detemir, glargine and degludec in addition to metformin and glimepiride therapy.

Comparison of treatment with insulin detemir and NPH in women with gestational diabetes mellitus: glycemic control and pregnancy outcomes. A retrospective study

PurposeThe objective of this retrospective study was to compare glycemic control, pregnancy outcomes, and neonatal outcomes in women with gestational diabetes mellitus (GDM) treated with (a) insulin detemir and (b) insulin neutral protamine Hagedorn (NPH).MethodsA total of 192 women with GDM were included in the analysis. Ninety-eight women received detemir, while 94 women received NPH. Data regarding medical history, glycemic control, and time and mode of delivery, as well as neonatal outcomes, were recorded.ResultsBaseline characteristics were comparable between the two groups. There were no differences with respect to the week of insulin initiation, total insulin dose, duration of insulin therapy, daily insulin dose/weight in early and late pregnancy, or the number of insulin injections per day. Maternal overall weight gain during pregnancy and weight gain per week did not differ either. The detemir group had slightly lower HbA1c levels at the end of gestation [median: det 5.2% (33 mmol/mol) vs NPH 5.4% (36 mmol/mol), p=0.035). There were no cases of hypoglycemia or allergic reactions in the two groups. There were also no differences regarding neonatal outcomes according to the available data, given that data in some cases were missing.ConclusionThe use of insulin detemir was found to be equally effective and safe compared to NPH in women with GDM.

A UK national survey of enteral feed use in people with diabetes 2022.

Enteral feeding is commonly used to manage a variety of medical conditions in hospitals. For people with diabetes this can present a specific challenge for glucose management. To address gaps in our understanding of modern enteral feeding outcomes and to help with the development of more specific guidance on maintaining glycaemic control, we conducted a national survey on the management of enteral feeding against the standards in the nationally adopted Joint British Diabetes Societies for Inpatient Care (JBDS) guidelines. A questionnaire was developed using the 2018 JBDS guideline as a template this questionnaire was sent out by email to all 220 UK specialist diabetes teams. Databases of Diabetes UK, the Association of British Diabetologists (ABCD) and the Diabetes Inpatient Specialist Nurse UK Group were used. Twenty-six hospitals responded, 11 had guidelines for the management of insulin with enteral feeding. There were three main feed regimens used: continuous 24-h feeding, a single feed with one break in 24 h, or multiple feeds in 24 h. There were five regimens in common use: premixed insulin, isophane insulin, analogue basal insulin, variable rate intravenous insulin or basal bolus insulin. Overall glucose control was poor for all regimens and combinations. Continuous feed showed better glucose control than a single feed with a break, mean (±SD) glucose 12.4 mmol/L (5.6) versus 15.1 mmol/L (6.9) p < 0.005, but no group showed optimal control. Managing diabetes control during enteral feeding remains a challenge. Our survey showed that glucose control during this treatment is suboptimal.

Examining the Effects of Hyperbaric Oxygen Therapy on the Cardiovascular System and Oxidative Stress in Insulin-Treated and Non-Treated Diabetic Rats.

This study explored the effects of hyperbaric oxygen therapy (HBOT) on the cardiovascular system and oxidative stress in streptozotocin-induced diabetic rats. Wistar albino rats were divided into four groups: DM group (diabetic rats), DM+HBOT group (diabetic rats exposed to HBOT for 1 h daily, five days a week, at 2.8 atmosphere absolute (ATA) with 100% oxygen for two weeks), DM+INS group (diabetic rats treated with neutral protamine hagedorn (NPH) insulin at a dosage of 3-5 U/day), and DM+HBOT+INS group (diabetic rats treated with both NPH insulin and HBOT for two weeks). Evaluations included glycemic control, oxidative stress parameters, and cardiac function measurements. NPH insulin treatment reduced blood glucose levels, although normoglycemia was not achieved. The DM+HBOT+INS group demonstrated the lowest pro-oxidative marker levels. NPH insulin treatment improved cardiac function, and combination therapy effectively restored cardiac function in diabetic animals. NPH insulin treatment reduced hyperglycemia and improved cardiac function in diabetic rats. The combined approach of NPH insulin and HBOT resulted in decreased pro-oxidative markers. These findings provide valuable insights for managing cardiovascular complications and oxidative stress in diabetes.

Efficacy of Glargine Insulin Compared with Neutral Protamine Hagedorn Insulin in Patients with Type 2 Diabetes not Controlled with Oral Hypoglycemics: A Cohort Study

Objective: To compare the efficacy of Glargine Insulin with Neutral Protamine Hagedorn (NPH) Insulin in patients with uncontrolled type 2 diabetes with oral hypoglycemic.&#x0D; Study Design: Prospective cohort study.&#x0D; Place and Duration of the Study: Railway Hospital, Rawalpindi Pakistan, from Nov 2020 to Jul 2021.&#x0D; Methodology: All patients aged 30-70 years of either gender, presented with uncontrolled diabetes mellitus on oral hypoglycemic for ≥1 year were enrolled. Patients were divided into Insulin Glargine and injection NPH subcutaneously by lottery method. In both groups, patients were compared for a reduction in HbA1c level after three months of treatment with Insulin. The efficacy was achieved after three months based on a&gt;1% HbA1c level reduction compared to baseline HbA1c.&#x0D; Results: The efficacy of Glargine Insulin was found to be significantly higher, 66(66%), as compared to NPH Insulin, 43(43%) (p-value = 0.002). After adjusting for all other covariates, the efficacy of Glargine Insulin was 3.81 times higher as compared to NPH Insulin (aOR 3.81, 95% CI 1.93-7052). Furthermore, efficacy was 6.95 times higher in patients with ≤25 kg/m2 BMI (aOR 6.95, 95% CI 3.16-15.30), 2.52 times higher in patients with ≤16 years of type 2 diabetes (aOR 2.52, 95% CI 1.30-4.87), 2.77 times higher in patients living in urban areas (aOR 2.77, 95% CI 1.43-5.36).&#x0D; Conclusion: The efficacy of Glargine Insulin was found to be considerably higher than NPH Insulin in patients with type 2 diabetes not controlled with oral hypoglycemia.Keywords: Efficacy, Glargine insulin, NPH insulin, Type 2 diabetes.

Intranasal insulin for COVID-19-related smell loss.

Quantitative (hyposmia and anosmia) and qualitative (phantosmia and parosmia) olfactory disorders are common consequences of COVID-19 infection found in more than 38% of patients even months after resolution of acute disease. SARS-CoV-2 has tropism for angiotensin-converting enzyme 2 (ACE2) in the respiratory system, suggesting that it is the mechanism of damage to the olfactory neuroepithelium and of involvement at the central nervous system. The olfactory bulb is the organ with the highest insulin uptake in the central nervous system. Insulin increases the production of Growth Factors (GF); therefore, in this study, the administration of intranasal insulin is proposed as a viable treatment for olfactory disturbances. The aim of this study was to obtain improvement in olfaction after 4 weeks of intranasal insulin administration in a group of patients presenting chronic olfactory disturbances secondary to COVID-19 infection, quantified using the Threshold, Discrimination, and Identification (TDI) score based on the Sniffin Sticks®. Experimental, longitudinal, prolective and prospective study of patients with a previous diagnosis of COVID-19 in the last 3-18months and who persisted with anosmia or hyposmia. The sample size was calculated with "satulator". The intervention was performed from January to May 2022. Throughout four appointments, a baseline olfactory measurement was obtained using the TDI score based on the Sniffin Sticks® test. In the first three appointments, Gelfoam® cottonoids soaked in 40IU of NPH insulin were placed on the nasal roof of each nostril for 15min. Descriptive statistics, student's paired t test and a multiple linear regression were utilized to ascertain statistical significance of the outcome on the TDI score obtained on the fourth and final appointment. 27 patients were included in the study. Table 1 summarizes the sample characteristics. The results exhibit that 93% of the sample had an improvement. The initial mean TDI score was 67% (63-71) compared to the final mean of 83% (80-86, p < 0.01). TDI subsection analysis is shown in Table 2. There was no significant difference in pre-intervention and post-intervention glucose measurements after the intranasal insulin administration. The administration of intranasal insulin has promising results, pointing towards an alternative of treatment for chronic olfactory disturbances secondary to neuroepithelial damage caused by upper respiratory tract infections. Furthermore, this is the first study to use a three-point assessment of olfaction in post-COVID-19 patients, while using the Sniffin Sticks® TDI score adapted to Latin Spanish.

Refrigerated multi-dose insulin vials remain sterile through 6 months of use.

To evaluate sterility in refrigerated multi-dose insulin vials through 6 months of routine aspiration. Twelve vials of insulin, six of insulin glargine U100 (Lantus®, 10 mL multi-dose vial, Sanofi, Bridgewater, NJ) containing the preservative metacresol, and six of protamine zinc insulin U40 (ProZinc®, 10 mL multi-dose vial, Boehringer Ingelheim, Duluth, GA) containing the preservative phenol, were refrigerated and aspirated twice daily for 6 months, using a new insulin syringe each time. Three vials of each insulin type were wiped with a single-use alcohol swab before sampling. Three times weekly, aspirated samples were inoculated in Tryptic Soy Broth enrichment media and incubated for evidence of microbial growth. Positive broth was cultured and speciated. Endpoints were microbial vial contamination (defined as three consecutive positive cultures of the same organism) and completion of the six-month study period. Microbial contamination was not identified in any vial throughout the study period. A total of 454 aspirated samples were cultured, one of which exhibited non-repeatable growth of Staphylococcus epidermidis. This vial was prematurely lost to breakage after 59 culture samples (29 after the positive growth). Refrigerated phenol- and metacresol-containing multi-dose insulin products carry minimal risk for iatrogenic infection through 6 months of use, regardless of alcohol swab preparation.

Neonatal and Maternal Outcomes of Insulin Detemir versus Neutral Protamine Hagedorn for Diabetes Mellitus in Pregnancy

Background and objectives: Diabetes in pregnancy can lead to severe neonatal and maternal adverse events. Moreover, there is an increase in GDM prevalence. Therefore, we aimed to compare insulin detemir (IDet) with the neutral protamine Hagedorn (NPH) in diabetic pregnant women. Methods: We searched four electronic databases until August 2021: PubMed, Scopus, Web of Science, and Cochrane. We included randomized controlled studies that compared IDet with NPH in diabetic pregnant women. We extracted both maternal and neonatal outcomes, and used RevMan software to conduct the analysis. Results: A number of five studies were included. The analysis showed a significantly lower risk of hypoglycemic events during pregnancy in the IDet group than the NPH group [RR=0.6, 95% CI [0.43, 0.84], p=0.003], and a higher gestational age (GA) at delivery in the IDet group than the NPH group [MD= 0.28, 95% [0.02, 0.55], p=0.03]. On the other hand, the analysis revealed non-significant differences between IDet and NPH in terms of birth weight, congenital anomalies, neonatal hypoglycemia, preterm delivery, and others. Conclusion: Insulin detemir (IDet) was preferred over neutral protamine Hagedorn (NPH) in terms of showing lower rates of hypoglycemic events during pregnancy and a higher gestational age at delivery. Meanwhile, there were non-significant variations between them when it comes to neonatal outcomes, such as weight at birth, congenital anomalies, or neonatal hypoglycemia.

Increased Apoptosis in Subcortical Regions of The Visual Pathway in Offspring Born to Diabetic Rats.

Diabetes in pregnancy is a prevalent disease that can affect the central nervous system of the fetus by hyperglycemia. This study aimed to investigate the impact of maternal diabetes on neuronal apoptosis in the superior colliculus (SC) and the lateral geniculate nucleus (LGN) in male neonates born to diabetic mothers. In this experimental study, female adult rats were separated into three groups: control, diabetic (induced using an intraperitoneal injection of streptozotocin), and insulin-treated diabetic [diabetes controlled by subcutaneous neutral protamine hagedorn (NPH)-insulin injection]. Male neonates from each group were euthanized on 0, 7, and 14 postnatal days (P0, P7, and P14, respectively), and apoptotic cells were identified using TUNEL staining. The numerical density per unit area (NA) of apoptotic cells was significantly higher in SC and the dorsal LGN (dLGN) in neonates born to the diabetic rats compared to the control group at P0, P7, and P14. However, insulin treatment normalized the number of apoptotic cells. This study demonstrated that maternal diabetes increased apoptosis in dLGN and SC of male neonates at P0, P7, and P14.

1851-PUB: Intractable Diabetic Ketoacidosis with Enfortumab Vedotin

Enfortumab Vedotin (EV) is an antibody-drug conjugate for metastatic urothelial carcinoma. Hyperglycemia and diabetic ketoacidosis (DKA) have been reported in patients using EV. The incidence increases with higher BMI. The one case report available on the association between EV and DKA resulted in development of multiorgan failure and death. This case, however, describes a positive outcome with recovery from DKA. We present a case of a 59 year-old Caucasian woman with morbid obesity, prediabetes and recurrent metastatic urothelial cell carcinoma who presented with hyperglycemia after 2 doses of EV. Labs were indicative of DKA without an infectious etiology. She was admitted to the ICU for intravenous insulin drip treatment. Hyperglycemia and ketosis persisted despite using a maximum insulin drip rate of 60 units/hour. Starvation ketosis was a factor, so a diet was started. On day 2, NPH insulin and prandial lispro were added along with the insulin drip, resulting in a total daily insulin dose of 1660 units. Nevertheless, hyperglycemia persisted. U-500 regular insulin was initiated and by day 4, the patient received a total of 2940 units of insulin in one day with normalized serum ketones. Insulin drip requirements decreased with blood glucose controlled solely on subcutaneous insulin. She remained euglycemic, so U-500 insulin was switched to daily glargine. Eventually, she was off all insulin and maintained blood glucose below 130 mg/dL. Work up for insulin resistance included a C-peptide of 42.6 ng/mL (normal 1.1-4.4) with glucose of 230 mg/dL, negative glutamic acid decarboxylase 65 and insulin antibodies, and a glucagon level of 213 pg/mL (normal ≤80) with glucose of 220 mg/dL. Although the mechanism by which EV causes hyperglycemia is not known, this case illustrates that hyperglycemia was due to severe insulin resistance associated with EV. Understanding this, along with glycemic effects of targeted therapies with Vedotin are necessary to investigate the causal mechanism and treatment for EV related hyperglycemia/DKA. Disclosure A.Elahi: None. J.Duron: None. T.Porter: None.

990-P: Estimating the National Costs of T2DM in the UK within the Context of Contemporary Guidelines

Background: The updated National Institute for Health and Care Excellence (NICE) type 2 diabetes (T2D) guidelines extend the recommendation of SGLT2 inhibitors (SGLT2i) for hyperglycaemia management to include their use in those with atherosclerotic cardiovascular disease (ASCVD), chronic heart failure (HF), chronic kidney disease (CKD) or high CVD risk. Our study estimates the potential cost consequence in the UK of the broad positioning of SGLT2i within updated guidelines (NG28-2022) versus previous guidelines (NG28-2015). Methods: The Cardiff T2D model was used to project lifetime outcomes and costs for T2D patients across established UK treatment pathways including metformin, sulfonylurea, DPP-4 inhibitors and NPH insulin with or without SGLT2i combination to reflect former vs. updated guidelines. Analyses were conducted in four subgroups (ASCVD, HF with reduced ejection fraction (HFrEF), CKD, high CVD risk). Projected outcomes were extrapolated to national level using population estimates from NICE’s guideline companion resource impact report. Results: Predicted lifetime costs for 1.7 Mn SGLT2i eligible T2D patients in the UK were estimated at £87.1 Bn with NG28-2022 compared to £101.7 Bn with NG28-2015. Net savings associated with NG28-2022 management of £14.56 Bn were attributable to comorbid CKD (£5.09 Bn), high CVD risk (£4.77 Bn), ASCVD (£3.96 Bn) and comorbid HFrEF (£0.74 Bn). Overall net savings were predicted despite an increase in pharmacy costs of £5.57 Bn. Changes in metabolic parameters and reduction in cardiovascular and kidney progression rates were predicted to prevent 20183 myocardial infarction events, 66651 HF events and 140303 events of end stage kidney failure. The magnitude of savings was a combination of event reductions and the number of eligible patients in subgroups. Conclusion: Our study indicates that uptake of SGLT2 inhibitors in line with NICE guidelines has the potential to improve health and be cost saving despite an increase in pharmacy costs. Disclosure P.Mcewan: Other Relationship; AstraZeneca. V.Foos: Other Relationship; AstraZeneca. R.Martin: Employee; AstraZeneca. J.Chen: Employee; AstraZeneca, Eli Lilly and Company.

Total pancreatectomy: Experience within an integrated health care system.

e16269 Background: Total pancreatectomy (TP) is most used for pancreatic adenocarcinoma (PC) but also for main duct intra-ductal papillary mucinous neoplasm. The authors report on a retrospective study of 61 patients who underwent TP in an integrated healthcare system. Methods: A retrospective review was performed of all patients treated with TP between January 2012 and December 2022. Patient demographics, tumor characteristics, treatment modalities, and mean overall survival (OS) were evaluated. Results: An intra-operative positive pancreatic neck margin for cancer or high-grade dysplasia was the most common indication for TP in 77% (47/61) of patients. The mean OS for patients with pancreatic cancer was 18 months, however, patients with a pre-op diagnosis of IPMN had a mean OS of 50 months. Multivariate analysis of PC without IPMN showed that neoadjuvant and NPH insulin were associated with a decrease in overall survival ( p&lt; .05). Overall HbA1c were higher in patients after one year after surgery for patients taking NPH (8.6) as opposed to an insulin pump (7.6) or Lantus (7.6) but not significant ( p= .346). Mean OS for patients with PC and type of insulin used was statistically significant at 24.4 months vs 13.1 months respectively for Lantus vs NPH ( p= .033). Conclusions: Conversion to TP for positive neck margins did not improve survival in patients who receive neoadjuvant chemotherapy but may be helpful in patients with IPMN. Blood sugar control after one year was similar among the various indication groups as well the type of insulin use. Although Lantus insulin was associated with improved overall survival for patients with pancreatic cancer, the exact reason is unclear and requires further studies.

Estimation of biphasic isophane insulin 30/70 by using validated RP-HPLC technique

Estimation of biphasic isophane insulin 30/70 by using validated RP-HPLC technique

Achievement of Target Glycemic Goal with Simple Basal Insulin Regimen in Women with Gestational Diabetes: A Prospective Cohort Study.

There is little evidence concerning the need to treat gestational diabetes (GDM) in the same way as pregestational diabetes. We evaluated the efficacy of the simple insulin injection (SII) regimen for achieving the target glucose goal without increasing adverse perinatal outcomes in singleton pregnant women with GDM. All subjects underwent self-monitoring of blood glucose (SMBG), and insulin therapy was indicated according to the SMBG profile. Insulin was initially started with the SII regimen, in which one daily injection of NPH insulin before breakfast was used, and another NPH injection was added at bedtime, if necessary. We used the target glucose as <95 mg/dL at fasting and <120 mg/dL postprandial and accepted <130 mg/dL for the latter. If the target glucose did not reach with the regimen, we switched to the multiple daily injection (MDI) with additional prandial insulin aspart. We compared the SMBG profile before delivery as well as the perinatal outcomes between the SII and MDI groups. Among 361 women (age 33.7 years, nullipara 41%, prepregnancy body mass index 23.2 kg/m2) with GDM, 59%, 18%, and 23% were in the diet-alone, SII, and MDI groups, respectively. Consequently, regarding women requiring insulin therapy, 43% were treated with the SII regimen throughout pregnancy. The severity of baseline hyperglycemia according to the SMBG data at baseline was the MDI>the SII>the diet group. The rate of achieving target glucose levels before delivery in the SII group at fasting, postprandial < 120 mg/dL and <130 mg/dL were 93%, 54% and 87%, respectively, which were similar to that in the MDI group (93%, 57%, and 93%, respectively), with no significant differences in perinatal outcomes. In conclusion, more than 40% of women with GDM requiring insulin therapy achieved the target glucose goal with this simple insulin regimen without any increase in adverse effects.

Modern Insulin, Device, and Technology: Tips For Clinicians

Insulin has been a lifesaving treatment for people with diabetes since its discovery in 1921. However, the way insulin is delivered evolved over time. Modern insulin, devices, and technology have transformed the management of diabetes and improved the quality of life for millions of people worldwide.Modern insulins are designed to match the needs of people with diabetes better. Traditional insulins, such as regular and NPH insulin, have a delayed onset and peak, making it difficult to manage blood sugar levels. Newer insulins, such as rapid-acting insulin analogs like aspart, glulisine, and lispro, have a faster onset and shorter duration of action, allowing for greater dosing and timing flexibility. Long-acting insulin analogs, like glargine and detemir, provide more consistent blood sugar control and less hypoglycemia risk.Insulin delivery devices have also advanced significantly. The most common device is the insulin pen, which looks like a large pen and uses disposable insulin cartridges. The pen has replaced traditional syringes and vials for many people with diabetes, offering greater convenience and ease of use. Insulin pumps are also becoming more popular, especially among people with type 1 diabetes. A pump delivers insulin through a catheter inserted under the skin, which can be programmed to provide a continuous infusion of insulin or a bolus dose before meals.Technological advancements have also revolutionized diabetes management. Continuous glucose monitoring (CGM) systems use a small sensor inserted under the skin to measure glucose levels every few minutes, providing real-time data to help people make more informed decisions about insulin dosing and food choices. Some CGM systems also offer alerts for high and low blood sugar levels, making it easier to avoid dangerous fluctuations. Automated insulin delivery systems, also known as closed-loop systems or artificial pancreas systems, use CGM data to automatically adjust insulin delivery, reducing the burden of constant monitoring and decision-making for people with diabetes.In summary, modern insulin, devices, and technology have greatly improved the management of diabetes, allowing for better blood sugar control and a better quality of life for people with diabetes. As technology continues to advance, the future of diabetes management looks promising. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 191

Maternal diabetes decreases the expression of GABAAα1, GABAB1, and mGlu2 receptors in the visual cortex of male rat neonates

AimsThis study examines the impact of maternal diabetes on the expression of GABAB1, GABAAα1, and mGlu2 receptors in the primary visual cortex layers of male rat newborns.Main Methods: In diabetic group (Dia), diabetes was induced in adult female rats using an intraperitoneal dose of Streptozotocin (STZ) 65 (mg/kg). Diabetes was managed by daily subcutaneous injection of NPH insulin in insulin-treated diabetic group (Ins). Control group (Con) received normal saline intraperitoneally rather than STZ. Male offspring born to each group of female rats were euthanized via CO2 inhalation at P0, P7, and P14 days after delivery and the expression of GABAB1, GABAAα1, and mGlu2 receptors in their primary visual cortex was determined using immunohistochemistry (IHC).Key Findings: The expression of GABAB1, GABAAα1, and mGlu2 receptors increased gradually with age in the male offspring born to Con group while the highest expression was detected in layer IV of the primary visual cortex. In Dia group newborns, the expression of these receptors was significantly reduced in all layers of the primary visual cortex at every three days. Insulin treatment in diabetic mothers restored the expression of these receptors to normal levels in their newborns. SignificanceThe study indicates that diabetes reduces the expression of GABAB1, GABAAα1, and mGlu2 receptors in the primary visual cortex of male offspring born to diabetic rats at P0, P7, and P14. However, insulin treatment can counteract these effects.

Long-acting insulin analogues and the risk of diabetic retinopathy among patients with type 2 diabetes: A population-based cohort study.

To determine whether the use of long-acting insulin analogues is associated with an increased risk of incident diabetic retinopathy (DR) among patients with type 2 diabetes. Using data from the Clinical Practice Research Datalink Aurum, this retrospective, population-based cohort study included patients with type 2 diabetes who initiated a long-acting insulin analogue (glargine, detemir, degludec) or Neutral Protamine Hagedorn (NPH) insulin. The primary outcome was incident DR. We used Cox proportional hazards models with inverse probability of treatment weighting to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DR with insulin analogues versus NPH insulin. There were 66 280 new users of long-acting insulin analogues and 66 173 new users of NPH insulin. The incidence rate of DR was 101.7 per 1000 person-years (95% CI, 98.7-104.8) for insulin analogues and 93.2 (95% CI, 90.0-96.5) per 1000 person-years for NPH insulin. Compared with the current use of NPH insulin, insulin analogues were not associated with the risk of incident DR (HR 1.04, 95% CI, 0.99-1.09). The adjusted HRs were 0.84 (95% CI, 0.66-1.07) for proliferative DR and 1.02 (95% CI, 0.97-1.08) for non-proliferative DR. Compared with NPH insulin, long-acting insulin analogues were not associated with the risk of incident DR among patients with type 2 diabetes. This finding provides important reassurance regarding the safety of long-acting insulin analogues with respect to incident DR.

An Unreported homozygous variant within Lipopolysaccharide responsive beige-like anchor (LRBA) gene in a child exhibiting with infantile type 1 diabetes mellitus

We report a patient who was born at term as the first son of consanguineous Saudi parents. He developed IDDM at the age of 7 months; the initial symptoms included fever and vomiting. The laboratory findings indicated pronounced ketoacidosis, initial fluid replacement with normal saline, followed by continuous IV insulin infusion. After a while, the baby was out of DKA. Our endocrinologist advised us to start administering S/C insulin NPH 1 unit BID. Fortunately, we suspected a primary immune deficiency acer a few days from the first presentation. The WES revealed A homozygous likely pathogenic variant was identified in the LRBA gene. The result is consistent with a genetic diagnosis of autosomal recessive CVID type 8 with autoimmunity. The LRBA protein regulates the expression of CTLA-4, which is a potent immune checkpoint receptor expressed by activated and regulatory by the T-cells. CTLA-4 blocks the stimulation/proliferation of T-cells and modulates immune responses.

The effect ofcold atmospheric plasma (NO) alone and incombination with NPH insulin onthe full-thickness excisional wound healing inadiabetic rat model.

This study was planned toinvestigate analternative treatment modality indiabetic wound healing. Inthis experimental study, the efficacy ofboth cold atmospheric plasma/nitric oxide (NO) and NPH insulin ointment, recently known tohave beneficial effects onwound healing, was investigated indiabetic wound healing. Twenty-four (24) diabetic rats were divided into four groups DC, DI, DNO and DINO (diabetic control, diabetic insulin, diabetic nitric oxide, diabetic insulin+ nitric oxide groups). Notreatment was applied tothe DC group, NPH insulin was applied tothe DI group, CAP/NO was applied tothe DNO group, and CAP/NO+ NPH insulin was applied tothe DINO group once daily for 14days. The wound area reduction and the wound contraction rate were calculated onthe basis ofthe tissue sections taken, and histopathological and genetic analyses were carried out. Compared tothe control group, exogenous NO gas was found tobe apotent antibacterial agent inthe diabetic wound healing, causing areduction inthe wound area (P=0.034), anincreased contraction rate (P=0.021), epithelialisation (P=0.02), collagen organisation (P=0.006) and areduction inthe number ofinflammatory cells (P=0.002). Asignificant increase inthe expression ofIL-8 mRNA was observed (P=0.026). Itwas concluded that NPH insulin alone contributes towound healing, but itis not necessary touse ittogether with exogenous NO gas.