Insulin-treated Group Research Articles

Troxerutin affects nephropathy signaling events in the kidney of type-1 diabetic male rats.

Objective:Nephropathy is known to be the leading cause of kidney failure in diabetic patients. Troxerutin, as a flavonoid component, could provide a novel protective strategy in the prevention of diabetic nephropathy. A large number of reports on the salutary effects of troxerutin inspired us to investigate its effect on the nephropathy signaling events (i.e., expression of TGF-β, miRNA192, and SIP1) in type-1 induced diabetic rats.Materials and Methods:50 male Wistar rats were divided into 5 groups including control group, sham group treated with troxerutin for 4 weeks, diabetic group induced by streptozotocin (STZ) injection, DI group including insulin-treated diabetic animals and DT group treated with troxerutin. Ultimately, rat kidneys were extracted, and the level of miR-192 (using qPCR), transforming growth factor-beta (TGF-β), and smad interacting protein 1 (SIP1) using an ELISA kit, was measured.Results:The level of TGF-β and miRNA192 significantly increased in the diabetic group. However, their expression levels decreased following the administration of troxerutin and insulin (p<0.05) compared to control group. SIP1 was down-regulated in the diabetic group, whereas a spike in the expression levels was observed after troxerutin administration compared to control and troxerutin groups (p<0.05). However, no significant difference was found in the effects of insulin and troxerutin on the level of miR-192, SIP1, and TGF- β. Conclusion:According to the previous literatures, during the progression of nephropathy, TGF-β represses SIP1 (the repression region in the collagen gene) by increasing the expression of miR-192. Ultimately, in this study, diabetes led to up-regulation of TGF-β while troxerutin proved to have a protective effect on the kidney by increasing SIP and lowering miR-192 levels.

Placental expression of endoglin, placental growth factor, leptin, and hypoxia-inducible factor-1 in diabetic pregnancy and pre-eclampsia

Objective To evaluate a level of expression of endoglin (Eng), leptin (Lep), placental growth factor (PlGF), and hypoxia-inducible factor-1alpha (HIF-1α) in placenta among women with pre-eclampsia and diabetes mellitus (DM), considering the method of glycemia correction and preconception care. Materials and methods A retrospective cohort study was conducted. A total of 124 women were divided into following groups: type 1 DM (n = 40), type 2DM (n = 31), gestational DM (n = 33), pre-eclampsia without DM (PE) (n = 10) and the control group (n = 10). The histochemical study was performed by using primary monoclonal antibodies to Eng, PlGF, Lep, and HIF-1α (Abcam, UK). Results The highest level of placental expression of Eng was observed in the PE group (20.34%). The same trend was also typical for T1DM (not planned) and insulin-treated groups: T2DM and GDM. An amount of cell with an PlGF expression was significantly higher in the control group (12.2%), while the lowest was observed in the pre-eclampsia group (1.18%) and T1DM (not planned) (1.26%). The placental leptin expression within each DM group was increased among the patients with unplanned pregnancy and those who received insulin therapy. We observed the lowest Lep expression in the PE group (6.3%). High level of HIF-1α expression was detected in T1DM (not planned) (30.44%) and PE (29.64%) as compared to the control group (11.62%). In T2DM and GDM insulin groups, the HIF-1α expression was significantly higher as compared to diet groups. Conclusion The obtained data show that DM and pre-eclampsia are associated with changes in angiogenic and metabolic placental factor expressions. The degree of changes depends on preconception care and the control of glycemia level during pregnancy.

Short- and long-term cardiovascular outcomes in insulin-treated versus non-insulin-treated diabetes mellitus patients after percutaneous coronary intervention: A systematic review and meta-analysis

AimsThis study aims to assess differences in severity of short-term (<1 year) and long-term (≥1 year) adverse CV outcomes after PCI in insulin-treated vs. non-insulin-treated diabetes mellitus (DM) patients. MethodsA systematic search on Pubmed and Embase led to the incorporation of 29 studies that compared post-percutaneous coronary interventional outcomes in insulin-treated and non-insulin-treated diabetes mellitus. Diabetes mellitus (type 2) was defined as fasting blood glucose (FBG) level of >7.0 mmol/L or with an oral glucose tolerance test (OGTT) level of >11.1 mmol/L at least on two separate occasions. Adverse CV outcomes were assessed in insulin-treated and non-insulin-treated DM after the PCI procedure considered for the analyses were mortality, MACE, TLR, TVR, MI, stent thrombosis, target lesion failure (TLF), and need for-post PCI CABG. Data were pooled and analyzed using Review Manager 5.3, and risk ratios (RR) with respective 95% confidence intervals (CI) were calculated.The statistical analyses were carried out by Review Manager v.5.3, and the data were pooled using a random-effects model. Risk ratios (RRs) with 95% confidence intervals (CI) were reported along with forest plots. The chi-square test was performed to assess for differences between the subgroups. Heterogeneity across studies was evaluated using Higgins I2 statistics. Visual inspection of the funnel plot and Begg's regression test were used to assess publication bias. ResultsA total of 40,527 patients (11742 in the Insulin-treated diabetes mellitus group and 28785 in the non-insulin-treated DM group) who underwent PCI were included. The pooled analysis of short-term follow up outcomes preceding PCI demonstrated a significantly higher risk of mortality (RR = 1.75 [1.24,2.47]; p = 0.002), MI (RR = 1.81[1.14,2.87]; p = 0.01], stent thrombosis (RR = 1.63[1.13, 2.35]; p = 0.009) and target lesion revascularization (TLR) (RR = 1.29[1.02,1.63]; p = 0.03) in insulin-treated DM patients. Similarly, analysis of long-term follow-up studies depicted a significantly higher risk mortality (RR = 1.55 [1.22, 1.97]; p = 0.0003), MI (RR = 1.63 [1.35, 1.97]; p=<0.00001), MACE (R = 1.47 [1.31, 1.65]; p=<0.00001), stent thrombosis (RR = 1.54 [1.19,1.99]; p = 0.001), TLR (RR = 1.40 [1.18, 1.66]; p = 0.0001), target vessel revascularization (TVR) (RR = 1.35 [1.11, 1.64]; p = 0.003) in insulin-treated DM group after PCI versus non-insulin-treated DM patients. ConclusionDespite a tremendous technical success rate of multi-vessel stenting, people living with diabetes who were being treated with insulin had higher long-term, and short-term mortality rates, MI, TLR, TVR, and stroke compared to people living with diabetes who were being treated with means other than insulin and are more prone to detrimental cardiovascular outcomes.

5-Aminolevulinic acid combined with ferrous iron improves glucose tolerance in high-fat diet-fed mice via upregulation of glucose transporter 1.

Decreased mitochondrial metabolism suppresses glucose metabolism, resulting in obesity and diabetes. The present study aimed to investigate mechanisms underlying the 5-aminolevulinic acid (5-ALA) hydrochloride-mediated increase in glucose uptake in high-fat diet (HFD)-fed mice in vivo and C2C12 myotube cells in vitro. C57BL/6N male mice (20 weeks old) were fed either HFD or normal diet (ND) for 4 weeks. A total of five HFD-fed mice were orally administered with 300 mg/kg 5-ALA hydrochloride and 47.1 mg/kg sodium ferrous citrate (SFC; HFD + 5-ALA/SFC), whereas ND and other HFD-fed mice were orally administered with saline. After 4 weeks, these mice were intraperitoneally administered with 2 g/kg glucose and 3.2 mg/kg 2-deoxyglucose (2DG) for intraperitoneal glucose tolerance test (IPGTT) and glucose uptake test. Body weights, plasma glucose levels and the area under the curve of IPGTT were lower in mice treated with HFD + 5-ALA/SFC compared with in those treated with HFD alone. 2DG uptake in the gastrocnemius muscle and heart were more significantly improved in the HFD + 5-ALA/SFC mice compared with the HFD-fed mice. Furthermore, 5-ALA/SFC increased 2DG uptake in C2C12 cells to a similar level to the insulin-treated group. Moreover, it increased glucose transport (GLUT)1 translocation in the plasma membrane by 2.5-fold relative to the controls without affecting GLUT1 expression; however, it had no effect on GLUT4 translocation. Therefore, 5-ALA/SFC enhanced gastrocnemius and cardiac glucose uptake in HFD-fed mice, and upregulated GLUT1 translocation to the plasma membrane, but not GLUT4 in C2C12 myotube cells. Therefore, it could potentially be used as a novel drug for the treatment of diabetes.

Hsa_circ_0054633 association of C peptide is related to IL-17 and TNF-α in patients with diabetes mellitus receiving insulin treatment.

BackgroundChronic inflammation damaged the islet and resulted in dysfunction of T2D. Circular RNA is stable and better for biomarker in many diseases. Here, we aimed to identify potential circular RNA hsa_circ_0054633 that can be a biomarkers for the effects of insulin therapy in T2D.MethodsIn this retrospective case‐control study, patients were from Li Huili Hospital, Ningbo, China, from February 10, 2019, to August 15, 2019. We included 47 healthy adults, 46 new‐onset T2D with insulin resistance, and 51 patients with insulin therapy. Serum inflammation factors were tested by ELISA assays. We selected hsa_circ_0054633 as a candidate biomarker and measured its concentration in serum by qRT‐PCR. The Pearson correlation test was used to evaluate the correlation between this circRNA and clinical variables.ResultsClinical data indicated that serum C peptide was increased in T2D treatment with insulin. Serum hsa_circ_0054633 was decreased in insulin treatment group. Hsa_circ_0054633 was negative correlated with C peptide (r = −0.2841, p = 0.0433,). IL‐1 and IL‐6, IL‐17, and TNF‐α were higher in T2D patients and decreased after insulin treatment, only IL‐17 and TNF‐α showed a positive correlation to hsa_circ_0054633 (r = 0.4825, p < 0.0001, and r = 0.6190, p < 0.0001). The area under ROC curve was 0.7432, 0.5839, and 0.7573 for Hsa_circ_0054633, C peptide, and their combination.ConclusionHsa_circ_0054633 level was lower in T2D with insulin treatment than untreated and was a negative correlation with C peptide, and positively correlated with IL‐17 and TNF‐α, suggesting that hsa_circ_0054633 may be a potential early indicator of insulin treatment effect to improve inflammation condition.

Geriatri polikliniğine başvuran tip 2 diabetes mellituslu hastalarda kas gücü ve kas kütlesinin vücut kitle indeksi ve insülin tedavisiyle ilişkisi

Aim: The aim of this study was to investigate the hand grip strength and muscle mass of older patients with type 2 diabetes mellitus in relation to body mass index and insulin treatment.&#x0D; &#x0D; Materials and Methods: A total of 123 older patients with diabetes mellitus ≥65 years of age were admitted to geriatric outpatient clinic of a university hospital between October 2015 and October 2019. Demographic data, medical records, laboratory results, hand grip strength and muscle mass were derived from the hospital records, retrospectively.&#x0D; &#x0D; Results: The patients were grouped according to body mass index and usage of insulin treatment. There was a negative correlation between body mass index and hand grip strength (p = 0,002), and a positive correlation between body mass index and muscle mass index (p = 0,001). No significant differences for hand grip strength and muscle mass index were observed between insulin treatment group and non-insulin treatment group.&#x0D; &#x0D; Conclusion: In type 2 diabetes mellitus patients with normal weight and obesity, anthropometric differences should be considered to identify true sarcopenic patients. Assessment of muscle strength, and also evaluation of muscle quality might be more valuable than assessment of muscle mass for those patients

Metformin for gestational diabetes study: metformin vs insulin in gestational diabetes: glycemic control and obstetrical and perinatal outcomes: randomized prospective trial

Gestational diabetes that is not properly controlled with diet has been commonly treated with insulin. In recent years, several studies have published that metformin can lead to, at least, similar obstetrical and perinatal outcomes as insulin. Nevertheless, not all clinical guidelines endorse its use, and clinical practice is heterogeneous. This study aimed to test whether metformin could achieve the same glycemic control as insulin and similar obstetrical and perinatal results, with a good safety profile, in women with gestational diabetes that is not properly controlled with lifestyle changes. The metformin for gestational diabetes study was a multicenter, open-label, parallel arms, randomized clinical trial performed at 2 hospitals in Málaga (Spain), enrolling women with gestational diabetes who needed pharmacologic treatment. Women at the age of 18 to 45 years, in the second or third trimesters of pregnancy, were randomized to receive metformin or insulin (detemir or aspart). The main outcomes were (1) glycemic control (mean glycemia, preprandial and postprandial) and hypoglycemic episodes and (2) obstetrical and perinatal outcomes and complications (hypertensive disorders, type of labor, prematurity, macrosomia, large for gestational age, neonatal care unit admissions, respiratory distress syndrome, hypoglycemia, jaundice). Outcomes were analyzed on an intention-to-treat basis. Between October 2016 and June 2019, 200 women were randomized, 100 to the insulin-treated group and 100 to the metformin-treated group. Mean fasting and postprandial glycemia did not differ between groups, but postprandial glycemia was significantly better after lunch or dinner in the metformin-treated-group. Hypoglycemic episodes were significantly more common in the insulin-treated group (55.9% vs 17.7% on metformin; odds ratio, 6.118; 95% confidence interval, 3.134-11.944; P=.000). Women treated with metformin gained less weight from the enrollment to the prepartum visit (36-37 gestational weeks) (1.35±3.21 vs 3.87±3.50 kg; P=.000). Labor inductions (45.7% [metformin] vs 62.5% [insulin]; odds ratio, 0.506; 95% confidence interval, 0.283-0.903; P=.029) and cesarean deliveries (27.6% [metformin] vs 52.6% [insulin]; odds ratio, 0.345; 95% confidence interval, 0.187-0.625; P=.001) were significantly lower in the metformin-treated group. Mean birthweight, macrosomia, and large for gestational age and babies' complications were not different between treatment groups. The lower cesarean delivery rate for women treated with metformin was not associated with macrosomia, large or small for gestational age, or other complications of pregnancy. Metformin treatment was associated with a better postprandial glycemic control than insulin for some meals, a lower risk of hypoglycemic episodes, less maternal weight gain, and a low rate of failure as an isolated treatment. Most obstetrical and perinatal outcomes were similar between groups.

PENGARUH PEMBERIAN SARI TOMAT (Solanum lycopersicum L) DAN INSULIN TERHADAP KADAR GLUKOSA, KADAR LDL, KADAR KOLESTEROL DAN BERAT BADAN LAHIR TIKUS PUTIH STRAIN WISTAR (Rattus Norvegicus) BUNTING DENGAN MODEL DIABETES MELLITUS TIPE 2

Diabetes Mellitus is a chronic disease caused by abnormal working insulin, insulin secretion or both so that the body tends to have high glucose levels. Type 2 diabetes mellitus can cause elevated levels of LDL and cholesterol. Risks obtained by fetuses with type 2 diabetes can be in the form of macrosomia due to hyperglycemia and hyperinsulin in the body of the fetus. Insulin is the first choice pharmacological therapy for type 2 DM that can be given during pregnancy. Non-pharmacological therapy as recommended by the World Health Organization (WHO) on a healthy diet by increasing consumption of fruits and vegetables. Good fruit consumed for pregnant women with diabetes mellitus (DM) type 2 is tomatoes (Solanum lycopersicum L). The purpose of this study was to determine the administration of tomato extract (Solanum lycopersicum L) and insulin can affect glucose levels, LDL levels, cholesterol levels and birth weight of white wistar galur (Rattus norvegicus) pregnant women with type 2 diabetes mellitus models. experimental design using the pre post test only control group design and post test only control group design. Termination was done on the 17th day of pregnancy and then followed by measurements of LDL levels, cholesterol and birth weight. Data analysis using the One Way Anova test and Kruskal Wallis then continued with the Post Hoc test using. The results showed that there were significant differences between glucose levels, LDL levels, cholesterol levels and BW born in the insulin treatment group and the tomato juice treatment (p value = 0.00 &lt;α = 0.05). The conclusion of giving insulin and tomato juice affects a decrease in glucose levels, LDL levels, cholesterol levels and birth weight.

The Effect of Diabetes Mellitus, Insulin, and Thiazolidinediones on Bone Histomorphometry in Streptozotocin-induced Diabetic Postmenopausal Wistar Rats

Background: Osteoporosis is a metabolic skeletal disease with low bone mass and bone microarchitectural disorganization. Thiazolidinediones (TZD) increase insulin sensitivity through activation of peroxisome proliferator-activated receptor gamma (PPARγ). One of the most important side effects of this drugs is its effects on bone, especially in postmenopausal women. The purpose of this study was to evaluate the effect of diabetes mellitus (DM), insulin, and TZDs on bone in postmenopausal Wistar rats.&#x0D; Methods: Sixteen postmenopausal Wistar rats were divided into four groups: (i) control group, (ii) Streptozotocin-induced DM group without treatment, (iii) Streptozotocin-induced DM group with insulin therapy, and (iv) Streptozotocin-induced DM group receiving rosiglitazone. Pictures of the obtained samples were taken under computer-equipped photo-light microscope, and bone tissue ratios were calculated in an area of 1 mm2. In this area, trabecular thicknesses were measured from six randomly selected regions. In addition, femoral neck regions were determined by measuring the farthest distance.&#x0D; Results: Compared to the control group, trabecular thicknesses were decreased in the uncontrolled DM and rosiglitazone groups. In the rosiglitazone-treated group, trabecular thickness was decreased compared to the uncontrolled DM group. The histological examination of the bones showed that uncontrolled DM and rosiglitazone treatment negatively affected the osteoblast and osteocyte activity. Insulin-treated group had a similar histologic examination compared to the control group.&#x0D; Conclusion: Our study showed that DM had unfavorable effects on bones, and rosiglitazone further exerts this effect. However, the negative effect of DM may be neutralized with the use of insulin.&#x0D; Keywords: diabetes mellitus, bone, osteoporosis, bone histomorphometry, rosiglitazone, insulin, thiazolidinediones

Risk of early mortality and cardiovascular disease according to the presence of recently diagnosed diabetes and requirement for insulin treatment: A nationwide study.

Aims/IntroductionWe estimated the hazards of cardiovascular diseases (CVDs) and early all‐cause mortality in Korean adults according to the presence of recently diagnosed type 2 diabetes (type 2 diabetes for <5 years) and insulin use.Materials and MethodsWe used the Korean National Health Insurance Service–National Sample Cohort database (2002–2015) for this longitudinal population‐based study. Among adults aged ≥40 years without baseline CVD, individuals without diabetes or with recently diagnosed type 2 diabetes were selected (N = 363,919). The hazard ratios (HRs) for myocardial infarction (MI), stroke, and all‐cause mortality during follow‐up were analyzed according to three groups categorized by the presence of type 2 diabetes and insulin use.ResultsWithin a mean 7.8 years, there were 5,275 MIs, 7,220 strokes, and 15,834 deaths. The hazards for outcomes were higher in the insulin‐treated type 2 diabetes group than in the non‐diabetes group [HR (95% CI): 2.344 (1.870–2.938) for MI, 2.420 (1.993–2.937) for stroke, and 3.037 (2.706–3.407) for death], higher in the non‐insulin‐treated type 2 diabetes group than in the non‐diabetes group [HR (95% CI): 1.284 (1.159–1.423) for MI, 1.435 (1.320–1.561) for stroke, and 1.135 (1.067–1.206) for death], and higher in the insulin‐treated type 2 diabetes group than in the non‐insulin‐treated type 2 diabetes group [HR (95% CI): 1.914 (1.502–2.441) for MI, 1.676 (1.363–2.060) for stroke, and 2.535 (2.232–2.880) for death].ConclusionsRecently diagnosed type 2 diabetes patients showed increased risks of incident CVDs and premature mortality, and insulin‐treated group demonstrated an additional increase in the risks of these outcomes in adults with recently diagnosed type 2 diabetes, suggesting the need for intensified cardio‐protective interventions for adults with insulin‐treated type 2 diabetes.

Local insulin application has a dose-dependent effect on lumbar fusion in a rabbit model.

The purpose of this study was to determine if locally applied insulin has a dose-responsive effect on posterolateral lumbar fusion. Adult male New Zealand White rabbits underwent posterolateral intertransverse spinal fusions (PLFs) at L5-L6 using suboptimal amounts of autograft. Fusion sites were treated with collagen sponge soaked in saline (control, n=11), or with insulin at low (5 or 10 units, n=13), mid (20 units, n=11), and high (40 units, n=11) doses. Rabbits were euthanized at 6weeks. The L5-L6 spine segment underwent manual palpation and radiographic evaluation performed by two fellowship trained spine surgeons blinded to treatment. Differences between groups were evaluated by analysis of variance on ranks followed by post-hoc Dunn's tests. Forty-three rabbits were euthanized at the planned 6weeks endpoint, while three died or were euthanized prior to the endpoint. Radiographic evaluation found bilateral solid fusion in 10%, 31%, 60%, and 60% of the rabbits from the control and low, mid, and high-dose insulin-treated groups, respectively (p<0.05). As per manual palpation, 7 of 10 rabbits in the mid-dose insulin group were fused as compared to 1 of 10 rabbits in the control group (p<0.05). This study demonstrates that insulin enhanced the effectiveness of autograft to increase fusion success in the rabbit PLF model. The study indicates that insulin or insulin-mimetic compounds can be used to promote bone regeneration.

Diabetes Type 1 Negatively Influences Leydig Cell Function in Rats, Which is Partially Reversible By Insulin Treatment.

Type 1 diabetes mellitus (T1DM) is associated with impaired spermatogenesis and lower testosterone levels and epididymal weight. However, the underlying processes in the testis are unknown and remain to be elucidated. Therefore, the present study focused on the effects of T1DM on testicular function in a spontaneously diabetic rat model. BB/OKL rats after diabetes manifestation were divided into 3 groups: those without insulin treatment and insulin treatment for a duration of 2 and of 6 weeks. Anthropometrical data, circulating levels of gonadotrophins, testosterone, and inhibin B were measured. Intratesticular testosterone, oxidative stress, inflammation, and apoptosis were analyzed. Key enzymes of steroidogenesis were evaluated in the testis. Untreated diabetic rats had significantly lower serum follicle-stimulating hormone and luteinizing hormone levels. Serum and intratesticular testosterone levels significantly decreased in untreated diabetic rats compared to healthy controls. Key markers of Leydig cell function were significantly downregulated at the RNA level: insulin-like factor 3 (Insl3) by 53% (P = .006), Star by 51% (P = .004), Cyp11A1 by 80% (P = .003), 3Beta-Hsd2 by 61% (P = .005), and Pbr by 52% (P = .002). In the insulin-treated group, only Cyp11A1 and 3Beta-Hsd2 transcripts were significantly lower. Interestingly, the long-term insulin-treated group showed significant upregulation of most steroidogenic enzymes without affecting testosterone levels. Tumor necrosis factor α and apoptosis were significantly increased in the long-term insulin-treated rats. In conclusion T1DM, with a severe lack of insulin, has an adverse action on Leydig cell function. This is partially reversible with well-compensated blood glucose control. Long-term T1DM adversely affects Leydig cell function because of the process of inflammation and apoptosis.

Genipin and insulin combined treatment improves implant osseointegration in type 2 diabetic rats

BackgroundType 2 diabetes mellitus (T2DM) has a harmful effect on the stability and osseointegration of dental implants. T2DM induces mitochondrial damage by inhibiting AMPK signaling, resulting in oxidative stress and poor osteogenesis in the peri-implant bone area. Genipin is a major component of gardenia fruits with strong antioxidant, anti-inflammation, and antidiabetic actions, and it also can activate mitochondrial quality control via the AMPK pathway. The purpose of this study was to investigate the effects of genipin and insulin treatment on implant osseointegration in T2DM rats and explore the underlying mechanisms.MethodsStreptozotocin-induced diabetic rats received implant surgery in their femurs and were then assigned to five groups that were subjected to different treatments for three months: control group, T2DM group, insulin-treated T2DM group (10 IU/kg), genipin-treated T2DM group (50 mg/kg), and the genipin and insulin combination-treated T2DM group. Then, we regularly assessed the weight and glucose levels of the animals. Rats were euthanized at 3 months after the implantation procedure, and the femora were harvested for microscopic computerized tomography analysis, biomechanical tests, and different histomorphometric assessment.ResultsThe results indicated that the highest blood glucose and oxidative stress levels were measured for the T2DM group, resulting in the poorest osseointegration. The combination-treated T2DM group mitigated hyperglycemia and normalized, reactivated AMPK signaling, and alleviated oxidative stress as well as reversed the negative effect of osseointegration. There were beneficial changes observed in the T2DM-genipin and T2DM-insulin groups, but these were less in comparison to the combination treatment group.ConclusionOur study suggests that treatment with genipin in combination with insulin could be an effective method for promoting implant osseointegration in T2DM rats, which may be related to AMPK signaling.

Apps and the Woman With Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) affects 1–45% of pregnancies depending on the population and diagnostic criteria selected (1). A meta-analysis with 12 randomized controlled trials (RCTs) showed that GDM management improves pregnancy outcomes (2). GDM management involves counseling, dietary modification, physical activity, glucose monitoring, and, where glycemic thresholds are exceeded, supplemental pharmacological therapies. Implementation varies, with possible consequences for the pregnancy outcomes. For example, the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) and Maternal–Fetal Medicine Units Network (MFMUN) RCTs, the two largest GDM treatment trials, differed in their insulin use (20% vs. 8%, respectively) and outcomes (3,4). Within the MFNUM RCT, the median glucose achieved was 10–12 mg/dL (0.6 mmol/L) higher in the insulin-treated than the non–insulin-treated group, particularly after dinner, when 50% of the self–blood glucose monitoring results were over the target glucose (median glucose was 120 mg/dL [6.7 mmol/L]). The more self–blood glucose monitoring results occur above target, the greater the chance of an adverse pregnancy outcome. In one study, adverse outcomes occurred in 25% vs. 60% of births among those with none vs. >30% above-target results, respectively (5). There are multiple barriers to GDM management for women with GDM (6). Besides a range of socioeconomic, service, and access barriers, women may experience misunderstanding or confusion over the advice provided, as well as a range of emotional and psychological challenges. Meanwhile, the increasing number of women with GDM (7) has created greater pressure on health care providers to streamline their services with different models of care, often sharing management with non–diabetes service staff (8). New technologies …

Impact of Treatment with Metformin in Comparison with Insulin in Gestational Diabetes in Libyan Population a Randomized Controlled Study.

Background:The aim of this study was the comparison of the glycemic control and maternal outcomes in women affected with gestational diabetes mellitus (GDM) managed with metformin versus insulin.Materials and Methods:The participants included in this study were 140 women diagnosed with GDM. They were randomized into two groups, women included in the first group were treated with metformin and the women of the second group were managed with insulin.Results:The glycemic control was similar in both the treatment arms and the only noteworthy difference was found in the mean fasting blood glucose, which was significantly higher in the women receiving insulin as compared to the women receiving metformin. There were no substantial differences in the maternal outcome with the use of metformin compared to insulin in women with GDM.Conclusion:The incidence of operative delivery was higher in metformin-treated group, whereas the hospital admission rate was considerably elevated in insulin-treated group.

Catecholamines production by kidney tissue and mesangial cell culture is differentially modulated by diabetes.

Introduction:According to the International Diabetes Federation, the number of people with diabetes mellitus may reach 700 million in 2045. Catecholamines are involved in the regulation of several kidney functions. This study investigates the effects of hyperglycemia on catecholamines' metabolism in kidney tissue from control, diabetic, and insulin-treated diabetic rats, both in vivo and in vitro.Methods:Male Wistar-Hannover rats were randomized into: control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by a single injection of streptozotocin, and diabetic treated group also received insulin. After 60 days, blood and kidney tissue from all groups were collected for catecholamines' quantification and mesangial cells culture.Results:diabetic rats had lower body weight, hyperglycemia, and increase water intake and diuresis. Additionally, diabetes promoted a sharp decrease in creatinine clearance compared to control group. Regarding the whole kidney extracts, both diabetic groups (treated and non-treated) had significant reduction in norepinephrine concentration. In mesangial cell culture, catecholamines' concentration were lower in the culture medium than in the intracellular compartment for all groups. Norepinephrine, epinephrine, and dopamine medium levels were increased in the diabetic group.Conclusion:The major finding of the present study was that 8 weeks of diabetes induction altered the kidney catecholaminergic system in a very specific manner, once the production of catecholamines in the excised kidney tissue from diabetic rats was differentially modulated as compared with the production and secretion by cultured mesangial cells.

Associations Between Glucose Tolerance, Insulin Secretion, Muscle and Fat Mass in Cystic Fibrosis.

Background:A frequent comorbidity in cystic fibrosis (CF) is CF related diabetes (CFRD) caused by a gradual decline in insulin secretion. The reduction in the anabolic hormone, insulin, might explain the weight loss that precedes onset of CFRD. We investigated the association between muscle and fat mass in relation to glucose tolerance and insulin function.Methods:In a cross-sectional study with CF patients (⩾18 years), we conducted an oral glucose tolerance test and dual energy X-ray absorptiometry scan (DXA). Based on plasma glucose, glucose tolerance was defined as normal (NGT): 1-hour <11.1 mmol/L and 2-hour <7.8 mmol/L, impaired (IGT): 2-hour ⩾7.8 and <11.1 mmol/L or CFRD: 2-hour ⩾11.1 mmol/L. Insulin resistance (HOMA-IR) was derived from fasting levels of plasma glucose and plasma insulin, and fat-free and fat mass index (kg/m2) from DXA. Associations were evaluated using linear regression models adjusted for age, sex, and pancreas insufficiency.Results:Among 79 CF patients with exocrine pancreas insufficiency, impairment of glucose tolerance corresponded to reduced insulin secretion. In the IGT group the fat-free mass index (FFMI) was 1.2 kg/m2 (95% CI: [−2.3, −0.03] kg/m2, P = .044) lower compared to the NGT group. FFMI increased insignificantly by 0.4 kg/m2 (95% CI: [−0.6, 1.5] kg/m2, P = .422) among the insulin-treated CFRD group compared to IGT. Fat mass index (FMI) was not different between groups but tended to decrease with glucose tolerance impairment. For each 100 pmol/L increase in fasting insulin FFMI increased by 1.77 kg/m2 (95% CI: [0.21, 3.33] kg/m2/pmol/L/100) and FMI increased by 6.15 kg/m2 (95% CI: [3.87, 8.44] kg/m2/pmol/L/100). In multivariate analyses, HOMA-IR was positively associated with FFMI (β = 0.5 kg/m2/HOMA-IR, 95% CI: [0.08, 0.92] kg/m2/HOMA-IR, P = .021) and FMI (β = 1.5 kg/m2/HOMA-IR, 95% CI: [0.87, 2.15] kg/m2/HOMA-IR, P < .001).Conclusions:Muscle mass was significantly lower among participants with impaired glucose tolerance (IGT), while muscle mass was normalized among those treated with insulin.

Intranasal Insulin Reduces White Matter Hyperintensity Progression in Association with Improvements in Cognition and CSF Biomarker Profiles in Mild Cognitive Impairment and Alzheimer\u2019s Disease

BackgroundIntranasally administered insulin has shown promise in both rodent and human studies in Alzheimer’s disease; however, both effects and mechanisms require elucidation.ObjectiveWe assessed the effects of intranasally administered insulin on white matter health and its association with cognition and cerebral spinal fluid biomarker profiles in adults with mild cognitive impairment or Alzheimer’s disease in secondary analyses from a prior phase 2 clinical trial (NCT01767909).DesignA randomized (1:1) double-blind clinical trial.SettingTwelve sites across the United States.ParticipantsAdults with mild cognitive impairment or Alzheimer’s disease.InterventionParticipants received either twice daily placebo or insulin (20 IU Humulin R U-100 b.i.d.) intranasally for 12 months. Seventy-eight participants were screened, of whom 49 (32 men) were enrolled.MeasurementsChanges from baseline in global and regional white matter hyperintensity volume and gray matter volume were analyzed and related to changes in cerebral spinal fluid biomarkers, Alzheimer’s Disease Assessment Scale-Cognition, Clinical Disease Rating-Sum of Boxes, Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale, and a memory composite.ResultsThe insulin-treated group demonstrated significantly reduced changes in white matter hyperintensity volume in deep and frontal regions after 12 months, with a similar trend for global volume. White matter hyperintensity volume progression correlated with worsened Alzheimer’s disease cerebral spinal fluid biomarker profile and cognitive function; however, patterns of correlations differed by treatment group.ConclusionIntranasal insulin treatment for 12 months reduced white matter hyperintensity volume progression and supports insulin’s potential as a therapeutic option for Alzheimer’s disease.

Associating Insulin Instillation with Negative Pressure Wound Therapy Reduces Insulin Resistance in Diabetic Patients with Infected Foot Wounds

In this work we investigated whether a joint treatment with insulin instillation and negative pressure wound therapy (NPWT) would reduce insulin resistance (IR) in diabetic patients with infected diabetic foot ulcers (DFUs) and improve their healing. We also studied the effects of insulin+NPWT treatment on the inflammatory response coupled with wound healing. Seventy-five diabetic patients with infected DFUs were recruited and randomly divided into equal (n=25) groups treated respectively with NPWT alone, NPWT+insulin, and conventional dressings (controls). Thereafter, the ulcers’ healing progress was assessed. The serum levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-2 (IL-2), and Interleukin-6 (IL-6) were measured at 1 day before and at 7, 14, and 21 days after each treatment using specific double-antibody sandwich enzyme-linked immunosorbent assays (ELISA). Serum glucose was measured via a glucose-oxidase method, and serum insulin via radioimmunoassay. In each patient, IR was appraised via the Homeostasis Model Assessment (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). Our results showed that at 7, 14 and 21 days post-treatment, with respect to the control group the two NPWT-treated groups had (i) significantly (p &lt; 0.05) lower serum levels of TNF-α, IL-2 and IL-6; (ii) a significantly (p &lt; 0.01) greater reduction in IR; and (iii) significantly (p &lt; 0.05) higher wound healing rates. Moreover, at 14- and 21-days post-treatment, the NPWT+insulin-treated group had a significantly (p &lt; 0.05) higher wound healing rate than the NPWT alone-treated group. In conclusion, the combined NPWT+insulin instillation treatment gave superior results by improving wound healing, decreasing inflammation at the wounds surface, and reducing IR in diabetic patients with infected DFUs.

Type1 diabetes management and outcomes: A multicenter study in Thailand.

Aims/IntroductionThe Thai Type 1 Diabetes and Diabetes Diagnosed Before Age 30 Years Registry, Care and Network was established in 2014 and involved 31 hospitals. The objective of the registry was to evaluate glycemic control and complications of patients with type 1 diabetes.Materials and MethodsPatients’ demographics, clinical data, frequencies of daily self‐monitoring of blood glucose (SMBG), glycemic control and complications were collected.ResultsAmong the 1,907 type 1 diabetes patients, the mean age was 21.2 ± 11.3 years. The mean glycated hemoglobin level was 9.35 ± 2.41%, with significant variations among age groups (P < 0.001). Conventional insulin treatment and intensive insulin treatment were used in 43 and 57% of patients, respectively. Mean glycated hemoglobin levels were significantly higher in patients treated with conventional insulin treatment compared to those treated with intensive insulin treatment (9.63 ± 2.34 vs 9.17 ± 2.46%, P = 0.002). Compared to the conventional insulin treatment group, significantly more patients in the intensive insulin treatment group achieved good glycemic control (P < 0.001), and fewer had diabetic retinopathy (P = 0.031). The prevalence of microvascular complications increased significantly with age (P < 0.001). Multivariate analysis showed good glycemic control to be associated with age 25 to <45 years, intensive insulin treatment with SMBG three or more times daily and diabetes duration of 1 to <5 years.ConclusionsMost Thai type 1 diabetes patients were not meeting the recommended glycemic target. As a result of this study, the national program to improve the quality of diabetes treatment and education has been implemented, and the results are ongoing.