Background and Aims

Type 2 Diabetes (T2D) is a chronic disease that requires continuous medical attention and represents a therapeutic challenge beyond glycemic control. Glucagon-like Peptide-1 receptor analogues (GLP-1) have a favorable effect in modifying cardiovascular risk factors.

Methods

Comparison of three descriptive, retrospective cohort studies, conducted between June-2013 and June-2016, 52 week follow-up, including patients with uncontrolled T2D, with different therapies, who were added to the treatment GLP-1 analogues, in a high complexity center in the city Cali, Colombia. Three specific therapies where compared: Liraglutide 1.8 mg/day; exenatide 2 mg/week, and exenatide 2 mg/week plus dapagliflozin/metformina 10/2000 mg/day, respectively. Repeated measurements were made over time of glycated hemoglobin (A1C), weight, and blood pressure (BP)

Results

Characteristics and results are showed on Table 1. The mean age was 60.6 years. The onset of T2D was 6.2 years. Combination therapy showed an average decrease of: A1C of 1.8% for Liraglutide (IC 95%, 1.52-2.04; P<0.0001), 1.7% for exenatide (IC 95%, 1.45-1.94, p<0.000) and 0.70% for exenatide plus dapagliflozin/metformin (CI 0.58 to 0.82, p <0.001); weight loss of: 5.1 kg, 5.8 kg and 3.04 kg respectively; and decrease of systolic BP of: 6.7mmHg, 15.6 mmHg and 16.3 mmHg, respectively. The largest decrease in A1C occurred between first and second visit and no serious adverse events were observed.

Conclusions

GLP-1 analogues are a favorable therapeutic option for patients with uncontrolled T2D, with beneficial effect on body weight and BP with statistically significant results

Background and Aims

Less than 40% of people with type 2 diabetes mellitus (T2DM) present HbA1c levels <7%. Dapagliflozin has demonstrated an impact on cardiovascular outcomes, weight loss, and a reduction in blood pressure. Evidence that allows evaluating combination therapies is still scarce. We aim to evaluate the effectiveness of the use of dapagliflozin as an intensification therapy in triple therapy for the treatment of patients with uncontrolled T2DM.

Methods

A quasi-experimental study was conducted in 123 adult patients aged over 18 years, diagnosed with uncontrolled type 2 diabetes mellitus, who received dapagliflozin added to their dual base treatment: metformin plus glibenclamide (n = 32), metformin plus saxagliptin (n = 29), metformin plus exenatide (n = 28) and metformin plus insulin (n = 34).

Results

All 123 patients completed the 52-week follow-up. The mean age, according to the study group, fluctuated between 52.8 ± 9.2 and 57.4 ± 5.9 years. 52.8% were women. The Hispanic population represented the largest number of patients in all groups. The mean reduction in the change in differences in HbA_1c values, fasting plasma glucose (FPG), weight and blood pressure during the study period showed a linear trend of decrease from the start at 52 weeks statistically significant ( p-value = <0.001).

Conclusions

The addition of dapagliflozin as an intensification alternative to the dual therapy for uncontrolled type 2 diabetic patients, consistently improved FPG and HbA_1c, body weight and blood pressure, with statistically significant results.

Background and Aims

Less than 40% of people with type 2 diabetes mellitus (T2DM) present HbA1c levels <7%. Dapagliflozin has demonstrated an impact on cardiovascular outcomes, weight loss, and a reduction in blood pressure. Evidence that allows evaluating combination therapies is still scarce. We aim to evaluate the effectiveness of the use of dapagliflozin as an intensification therapy in triple therapy for the treatment of patients with uncontrolled T2DM.

Methods

A quasi-experimental study was conducted in 123 adult patients aged over 18 years, diagnosed with uncontrolled type 2 diabetes mellitus, who received dapagliflozin added to their dual base treatment: metformin plus glibenclamide (n = 32), metformin plus saxagliptin (n = 29), metformin plus exenatide (n = 28) and metformin plus insulin (n = 34).

Results

All 123 patients completed the 52-week follow-up. The mean age, according to the study group, fluctuated between 52.8 ± 9.2 and 57.4 ± 5.9 years. 52.8% were women. The Hispanic population represented the largest number of patients in all groups. The mean reduction in the change in differences in HbA_1cvalues, fasting plasma glucose (FPG), weight and blood pressure during the study period showed a linear trend of decrease from the start at 52 weeks statistically significant ( p-value = <0.001).

Conclusions

The addition of dapagliflozin as an intensification alternative to the dual therapy for uncontrolled type 2 diabetic patients, consistently improved FPG and HbA_1c, body weight and blood pressure, with statistically significant results.

Background and Aims

Diabetes mellitus is a chronic metabolic disorder that is characterized by defects in endogenous insulin secretion or action. Metformin is the first-line drug of choice for the treatment of type 2 diabetes (T2D). It exerts antidiabetic effects by reducing hepatic glucose production and increased peripheral glucose utilization through activation of AMP-activated protein kinase (AMPK). Naringenin, a flavonoid exerts antidiabetic effects by inhibition of gluconeogenesis through upregulation of AMPK, hence metformin-like effects.

To identify AMPK as a potential target of synthetic chalco-naringenin analogs and putative therapeutic applications.

Methods

Chalco-naringenin analogs, were synthesized, characterized by IR, ¹H-NMR and ¹³C-NMR. C2C12 and Chang cells were cultured in dulbecco's modified eagle medium (DMEM). MTT assay was used to determine cell viability and subjection to phospho-AMPKα (Thr172) sandwich ELISA Kit to determine phosphorylation of AMPK.

Results

Chalcones were successfully synthesized and characterized through ¹³C-NMR and ¹H-NMR spectroscopy. Docking scores of the chalcones suggested a good binding affinity of these compounds to AMPK. Cell viability as determined by MTT assays were found to be dose-dependent for all compounds, however 5k exerted reduced cell viability as compared to 5b. The effects of chalcones on AMPK phosphorylation were potentiated by co-treatment with metformin or naringenin.

Conclusions

The chalcones showed potential in expression of AMPK through computational chemistry, however in the in vitro model the effects of chalcones on AMPK were potentiated by metformin and naringenin. The chalcones could further be explored for their potential on AMPK activity in in vivo studies to develop therapeutic targets for the effective management of diabetes.

Background and Aims

Oxidative stress can significantly influence lower extremities microangiopathy development in patients with type 2 diabetes (T2DM). Total cysteine ​​and its various fractions levels can serve as an indicator of the plasma antioxidant potential. Cysteine various fractions levels ​​in patients with T2DM and microangiopathy of the lower extremities was the aim of this research.

Methods

60 men from 55 to 70 years old were examined: 20 patients with T2DM without vascular complications and 40 patients with vascular complications - microangiopathy of the lower extremities of the 1st degree. The control group included 20 healthy men. Methods of high-performance liquid chromatography were used.

Results

The level of total cysteine in patients with T2DM without complications decreased (1.76 times) compared to the control group level and relatively increased in T2DM patients with complications (1.16 times to the control group) . The level of the reduced cysteine ​​fraction in patients with complications decreased by 1.75 times to the group without complications. The level of the oxidized fraction increased both in the group without complications (1.88 times) and in the group with complications (2.04 times) relative to the control. The ratio of the reduced fraction to the oxidized fraction decreased by 2.43 times in the group without complications and by 3 times in the group with complications relative to the control.

Conclusions

The content of total cysteine ​​and its reduced fractions significantly decreases in patients with type 2 diabetes with complications in the form of microangiopathy of the lower extremities, which needs to be corrected with antioxidant drugs.

Background and Aims

Therapy of type 2 diabetes mellitus (T2DM) in the last 10 years has associated with the new drugs: glucagon-like peptide-1 receptor agonists (GLP-1ra), inhibitors of dipeptidylpeptidase type 4 (DPP-4i), inhibitors of sodium-glucose cotransporter type 2 (SGLT-2i).

To study modern approaches to therapy initiation in patients with T2DM the data from Moscow segment of Russian Federal Diabetes Register (MSRFDR) was analyzed.

The aim of the study was to analyze the structure of therapy initiation for newly diagnosed in 2018 T2DM based on MSRFDR.

Methods

Materials and methods: a cohort of patients with newly diagnosed in 2018 T2DM was formed from the MSFDR. Age, BMI, HbA1c, proportion of patients with HbA1c <7,0% were evaluated.

Results

Results: MSRFDR contains data of 21.832 patients with newly diagnosed in 2018 T2DM; 597 patients (2,7%) of this group didn’t receive therapy, 19.586 patients (89,7%) were on oral glucose-lowering drugs (OGLDs) and/or GLP-1ra and 1.649 patients (7,6%) – on insulin therapy.

The better glycaemic control parameters were observed on Met and DPP-4i. Glycaemic control parameters were significantly worse in SU and SGLT-2i groups (p<0,05).

Patients on 2 oral glucose-lowering drugs (OGLDs) therapy were divided into 2 groups. Group 1 included patients receiving Met + SU/Glinides (3.704 pts), Group 2 - patients on DPP-4i, GLP-1ra or SGLT-2i therapy (1.031 pts). Glycaemic control parameters were better in Group 2 [НвА1с - 7,5% and 8,1% (p<0,05)].

Conclusions

Conclusion:

1. The proportion of patients with the level of HbA1c<7,0% in the first year of therapy was the highest on OGLD monotherapy (53,1%).

2. Glycaemic control parameters on 2 OGLDs therapy were better if patients used DPP-4i, GLP-1ra or SGLT-2i.

Background and Aims

To investigate the efficacy of a new combination of four elements (Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, Vit. B12) contained in one pill in Diabetic Neuropathy (DN).

Methods

In current prospective, double-blind, placebo-controlled, age In current prospective, double-blind, placebo-controlled, age-matched study, 85 patients with Diabetes Mellitus Type 2 (DMT2), randomized in two groups: group A: n=43 received the pill with the combination of the four elements (SOD, ALA, B12, ACL) and group B: n=42 received placebo. The following methods for detecting DN and Autonomic Neuropathy (DAN) used: MNSI, Cardiovascular Autonomic Reflex Tests (CARTS). We measured using DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. We used a pain (PS) and a quality of life (QL) questionnaire, also.

Results

All values of laboratory tests and indices of measurements between the two groups did not differ at baseline A vs B including HbA1c (7.2±1.2 vs 6.8±1.2% p=0.207, Vit.B12 263±100 vs 299±155 pmol/L p=0.268). The following indices improved significantly in group A (baseline vs final): MNSIQ 6.6±1.6 vs 6.0±1.7 (p=0.003), QL 39.8±10.8 vs 36.2±9.8 (p<0.001), PAIN 20.6±7.9 vs 17.4±7.0 (p<0.001) and SNCV 32.5±23.8 vs 39.4±22.8 m/s (p=0.027), SNAP 6.2±5.1 vs 7.5±6.5 uV (p=0.031) improved significantly. Vit. B12 increased in group A (p<0.001) and was unchanged in group B.

Conclusions

In the current study after 12 months from the administration of the combination with the four elements in one pill in patients with DMT2 (group A), we observed an improvement in all indices of peripheral neuropathy including neurophysiological parameters, Pain and QL except for CARTS.

Background and Aims

Endoplasmic reticulum (ER) stress has been implicated in the loss of function and death of pancreatic β-cells in both types of diabetes. An important istep in the resolution of ER stress is the inhibition of protein synthesis. The aim of study was to determine how protein synthesis is repressed in pancreatic β-cells in response to ER stress by utilising selective translation initiation factor dependency of viral mRNAs. Such knowledge is important for a full understanding of β-cell biology in health and disease and how this might be targeted therapeutically.

Methods

48 h post-transfection the MiIN6 cells incubated for 4 h in the presence or absence of a thapsigargin(1mM).Cap-dependent and indenoedent were determined using the dual-luciferase reporter assay

Protein synthesis measured. by [³⁵S]methionine and trichloroacetic acid method .Data were analysed by two-tailed paired t-tests using GraphPad Prism .

Results

As EMCV translation occurs independently of eIF4E, and pRF (Fig 1)

As HCV translation occurs independently of eIF4E, eIF4B and eIF4A (fig2)

CrPV IRES translationis resistant to ER stress (Fig3).Thus ER stress-induced repression of protein synthesis is caused by the perturbation of an initiation factor or factors.

Treatment with thapsigargin for4,12 and 24 h inhibited protein synthesis , the PERKinhibitor restore it .(fig 4)

Conclusions

This work provides a deeper understanding into how ER stress represses protein synthesis in pancreatic β-cells which may be of importance in designing new anti-diabetogenic strategies.

Background and Aims

It is known how diabetes mellitus can reduce hand and ankle joints range of motion and modify their posture. The aim of this study was to investigate using a new method how diabetes affects hand and foot posture in young Type 1 Diabetes Mellitus (T1DM).

Methods

We enrolled 20 young T1DM patients: (M/F:11/9), mean age 13,8±3,8 yrs, BMI 19,5±4,7 kg/m², diabetes duration 4,6±3,6 yrs, mean HbA1c 8,2±1,2 %, and 46 young subjects practicing soccer and dance: (M/F:30/16), mean age 12,6±2,1 yrs, BMI 18,9±2,6 kg/m². In these subjects, we evaluated hand posture (analysis of frontal plane image of Prayer sign test). In particular, the inclination of the fifth metacarpal and phalanges bones were evaluated in addition to the angles at the metacarpophalangeal and interphalangeal joints. Ankle joint mobility and posture were evaluated (inclinometer and sagittal plane image) with patients on lying and standing position.

Results

The analysis of hand images showed the presence in diabetic patients of a higher extension of the fifth metacarpophalangeal joint (patients: 34,7±11,0°; control: 18,6±8,5°) and higher flexion of the proximal interphalangeal joint (patients: 11,0±5,1°; control: 0,4±9,8°).

In comparison to controls, the patientshowed a higher inclination of the fifth metacarpal joint (42,4±11,2° vs 34,4±8,4°; p<0,005) and a lower inclination of the proximal phalanx (4,9±6,0° vs 15,7±6,1°; p<0,001).

Conclusions

The results of this pilot study indicate that the metacarpophalangeal joint and the proximal interphalangeal joint take a different posture in patients with T1DM. Young patients with T1DM can show from the first years of disease onset abnormal posture of the hand.

Background and Aims

The aim of this study was to evaluate the presence of a relationship between the patients’ social networks (PSN), the daily physical activity performed (PAP)and the metabolic control maintained in young subjects with type 1 diabetes mellitus (T1DM).

Methods

Interviews were conducted in 16 subjects with T1DM(males/females: 7/9), mean age 15,5±3,8 yrs, duration of diabetes 6,6±4,9 yrs, mean HbA1c (baseline) 7,3±1,7% (year before) 7.3±1.6%, body mass index (BMI) 21,6±2,9 kg/m²and in 12 age and BMI matched to healthy control subjects.

Participants were asked to fill in an egocentric social network map, which was divided into 5 areas: family, school, health, leisure and sport activities, other.It was assigned a value ranging from 0 (none) to 5 (maximum) to define importance and frequency of the relationships reported. The PAP was evaluated by the Physical Activity Questionnaire (PAQ-C;PAQ-A).

Results

The analysis of the PSN showed that the frequency reported on the area of leisure and sport activities was significantly lower in the patient group in comparison to controls (4,2±1,8 vs 3,1±1,0; p<0,05). From the analysis of the two groups, the young patients investigated reported to attend significantly fewer sports clubs(3.3±0.8 vs 4.2±0.8, p<0.01) and have less contact with teammates (2.8±1.5 vs 4.2±1.3; p<0.05). However, they mainly attend hospital (2.0±1.1 vs 0.6±0.7; p <0.001) and friendly societies (1.5±1.1 vs 0.1±0.4; p<0.001).

Conclusions

The results of this pilot study showed that the analysis of PSN could contribute to improving knowledge and therefore providing additional information useful for a better management of these patients.

Background and Aims

An exploratory analysis of data from the global Phase 3a PIONEER programme (PIONEER 1–5, 7 and 8 trials) evaluated the efficacy of once daily oral semaglutide 3, 7, 14 mg versus comparators by duration of diabetes at baseline.

Methods

Patients in PIONEER 1–5, 7 and 8 (n=5657) were grouped according to diabetes duration (<5, 5–<10 and ≥10 years) and by trial. In the PIONEER trials, patients received oral semaglutide (3, 7 or 14 mg) or comparator (placebo, empagliflozin, sitagliptin or liraglutide). Endpoints were change from baseline in HbA_1c (%) and body weight (kg) at week 26 (week 52 in PIONEER 7).

Results

At baseline, mean HbA_1c (%) was similar across diabetes duration subgroups within trials, whereas mean body weight was higher and age was lower in the duration <5 years subgroup. Reductions in HbA_1c were generally greater with increasing oral semaglutide dose but were not affected by diabetes duration and there were generally no statistically significant interactions between treatment and diabetes duration (Table). Estimated treatment differences in HbA_1c (%) at week 26 (week 52 in PIONEER 7) were consistent across the diabetes duration subgroups.

Conclusions

Across the PIONEER trials, oral semaglutide improved glycaemic control versus comparators, with an effect that was consistent across subgroups of diabetes duration. These findings support the use of oral semaglutide across a broad population of patients with type 2 diabetes.

Background and Aims

Beeswax venom (BWV) formulation is composed of bee wax (BW) (98.29) and bee venom (BV) (1.71%) possesses various medicinally important molecule lead us to elucidate its antidiabetic property in high-fat diet (HFD) and low dose streptozotocin (STZ) induced type 2 diabetic rats.

Methods

Type 2 diabetes mellitus (T2DM) was induced by feeding HFD for 2 weeks followed by the injection of single dose of 35 mg/kg STZ. After 3 weeks of oral administration of BWV formulation (0.125, 0.250 and 0.500 mg/kg) and metformin (MET) 180mg/kg, the biochemical parameters such as serum glucose, serum insulin, lipid profile, liver marker enzymes was estimated. Furthermore, western blot analysis of liver peroxisome proliferator activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein (C/EBP- β) and CCAAT/enhancer binding protein-alpha (C/EBP-α) was performed. Histological analysis of pancreas was also studied.

Results

Oral administration of BWV formulation (0.125, 0.250 and 0.500 mg/kg) and metformin 180mg/kg significantly reduced the levels of serum glucose, total cholesterol (TC), triglycerides (TG), liver marker enzyme and significantly increased the serum insulin and body weight. Furthermore, BWV formulation treatment enhanced the liver PPAR-γ, C/EBP- β and C/EBP-α protein expression. At the same time histological analysis of pancreas showed significant amelioration of β-cell damage.

Conclusions

Our results suggest that BWV formulation regulated the abnormalities of glucose and lipid metabolism by its PPAR-γ agonist property in HFD low dose induced type 2 diabetic rats.

Background and Aims

Combinations of insulin glargine/lixisenatide (IGlarLixi) or insulin degludec/insulin aspart (IDegAsp) are considered treatment intensification in type 2 diabetes mellitus upon limited response to basal insulin. In the absence of head-to-head trials comparing the efficacy of IGlarLixi and IDegAsp, a meta-analysis based on phase III trials was conducted.

Methods

Two phase III trials (BOOST and LIXILAN) were included in this meta-analysis, with 366 eligible patients on IGlarLixi and 230 eligible patients on IDegAsp. Treatments were primarily compared in terms of estimated treatment difference (ETD) in glycated haemoglobin (HbA1c) change from baseline; in addition to changes in fasting and prandial plasma glucose (FPG and PPG), and self-monitoring blood glucose (SMBG) score changes. Hypoglycaemia incidence and weight changes were described.

Results

In a fixed-effect model controlling for HbA1c, and compared with IDegAsp, IGlarLixi was more effective at reducing levels of HbA1c (ETD 0.53% [95%CI 0.27;-0.79, P<0.0001]), PPG (ETD 2.65% [95%CI 1.96;3.34], P<0.0001), and body weight (ETD 1.73 kg [95%CI 1.09;2.47], P<0.0001). A higher proportion of patients on IGlarLixi achieved glycemic control (ETD 0.40 [95%CI -0.083;0.884], P<0.0001). FPG and SMBG changes were not significantly different between treatment groups.

Patients on IGlarLixi were also more likely to achieve HbA1c<7% than patients on IDegAsp (odds ratio [OR]=0.401 [95%CI -0.083;0.884], P<0.0001), with lower overall incidence of hypoglycaemia (OR=1.328 [95%CI 0.859;1.797], P<0.001).

Conclusions

In this trial meta-analysis, IGlarLixi seemed to be more efficient than IDegAsp in controlling HbA1c and PPG and was associated with greater weight loss and lower incidence of hypoglycaemia.

Background and Aims

Gestational diabetes (GD) is a common pregnancy-related disorder, coupled with altered placental vascular reactivity and has severe consequences for fetal growth. Our previous findings revealed a potentially safe hypoglycemic action of Cinnamaldehyde (Ci) on a rat-model that mimics human GD-pathophysiology. This study aims to provide an integrated approach to unravel placental responses to GD through transcriptional, biochemical and histopathological analyses and how Ci mitigates these effects in comparison to glyburide/metformin-HCl (Gly/Met).

Methods

We used the fatty-sucrosed diet/streptozotocin (FSD/STZ)-rat model of GD. Oral doses of Ci (20 mg/kg) or Gly/Met (0.6+100 mg/kg) were given daily, from one week before mating onwards. On day 20 of pregnancy, maternal and fetal blood was collected for glucose, insulin, erythropoietin (EPO) and hematocrit (Hct) measurements. Placentae were taken for transcriptome, metabolite and enzymatic antioxidant profiling. Also, H&E and PAS-staining were used for histopathological assessments. Fetal liver was excised for iron content evaluation.

Results

Fetuses of GD-group showed a significant drop in Hct level, a 4-fold increase in serum-EPO and 28% reduction of their liver-iron content compared to controls, which indicates fetal hypoxia. Interestingly, both Ci and Gly/Met reduce GD-hyperglycemia but only Ci mitigates fetal hypoxia. Placental transcriptomic changes of diabetic and Gly/Met-treated groups revealed overrepresented pathways of angiogenesis, response to hyperoxia and reactive oxygen species biosynthesis with evidences of O₂-consumption for glucose oxidation. Biochemical assays confirmed these findings. Additionally, Ci prevents distinct structural alterations of diabetic placenta that predominantly include labyrinth hypervascularization and glycogen increment.

Conclusions

Ci counteracts GD-induced fetal hypoxia by improving placental function.

Background and Aims

Adiponectin and its receptors are involved in various physiological regulations including glucose homeostasis and fatty acid oxidation, and adiponectin deficiency is closely related to chronic metabolic diseases.

Methods

A novel peptide agonist to AdipoR1, BHD1028, was designed and evaluated both in vitro and in vivo systems.

Results

BHD1028 facilitated AMPK activation in C2C12 myotube and significantly enhanced glucose uptake (p<0.05) in insulin resistance-induced C2C12 cells.

A glucose lowering profile after single dose of s.c. injecting 50, 100 and 200 μg/Kg of pegylated BHD1028 (PEG-BHD1028) in db/db mice showed significantly lower than that of control animals during a 12-hour period without causing hypoglycemia. Besides, an OGTT was performed in db/db mice following a 1g/Kg of glucose oral load. The treated animals (s.c. injection, 1 and 50 μg/Kg) showed significantly lower glucose (p<0.05) and insulin (p<0.01) levels than control group, indicating an effective glucose homeostasis of PEG-BHD1028 by ameliorating the insulin resistance.

Subchronic effect of the drug following daily s.c. injection of 1, 5, 25, 50 and 200 μg/Kg in db/db mice for 3 weeks showed a significant plasma glucose lowering effect in the group received 50 and 200 μg/Kg from day 16, the weight loss in the range of 6-8% (p<0.01) on day 21 in the animals received 5, 25 and 50 μg/Kg. HbA1c levels of all treated groups were significantly lower than control animals (p<0.05) on day 21.

Conclusions

These results indicate that PEG-BHD1028 could be a potential therapeutic agent for type 2 diabetes, obesity, NASH, and other metabolic diseases.

Background and Aims

Sodium–Glucose Cotransporter Inhibitors (SGLTi) are antidiabetic medications which act by inhibiting tubular glucose reabsorption. EDKA is a serious complication of their use. (HNFN1A)-MODY patients are characterized by reduced tubular glucose reabsorption. A single dose of dapagliflozin, an SGLT2i, has shown to induce higher glycosuria in (HNFN1A)-MODY compare to T2D patients.

Methods

A 51 years old female, diagnosed with (HNFN1A)-MODY at the age of 17, presented to the ER complaining of abdominal pain. She had HbA1c 7,6% and BMI=35,7 Kg/m2 (88 Kg) 45 days ago. Due to peripheral edema, her treatment changed from pioglitazone 45 mg/d, metformin 2000 mg/d and glimepiride 6 mg/d to dapagliflozin/metformin 10/2000/d and dulaglutide 1,5 mg/qw. During this period her SMBG was adequate, she lost 8 Kg and she experienced a remarkable loss of appetite.

Results

On admission, she appeared dehydrated. Laboratory investigation revealed anion gap metabolic acidosis (pH: 6,9), Lact: 2,3 mmol/L, serious ketonuria, CRP: 0,2 mg/dL, blood glucose: 195 mg/dl and HbA1c 7%. She was diagnosed with EDKA and was hospitalized. After acid-base balance and dehydration were restored, and any infection or concomitant illness were excluded, she was discharged two days later, on treatment with insulin glargine 12 iu/d, metformin 2000mg/d and glimepiride 6mg/d. Two months later she continues with the same regimen (c-peptide: fasting 0.822 mg/dL and 6 min post-glucagon 1,38 mg/dL, HbA1c=6,9%).

Conclusions

We attributed this case of EDKA to dapagliflozine. Futhermore, the prone to ketogenesis diet with reduced calories might have played a precipitating role. Clinicians should use SGLT2i with great caution in (HNFN1A)-MODY patients.

Background and Aims

Lipoatrophic diabetes is an exceptional form of diabetes mellitus. His current care in Tunisia is difficult.

Methods

We report the case of a patient with lipoatrophic diabetes associated with schizophrenia.

Results

This is a 28-year-old patient hospitalized for ketotic decompensation of her diabetes. She comes from a consanguineous marriage of second degree, diabetic from then 5 years, with the antecedents of acute pancreatitis with repetition and schizophrenia since two years. No other pathological history, including no antiretroviral therapy. The clinical examination shows a BMI of 22.03 kg / m², a whole height of 95 cm, with partial lipoatrophy that would be installed since adolescence characterized by slender limbs and fat accumulation at the abdominothoracic level, hypertrophy bilateral parotid, acanthosis nigricans, smooth lower hepatomegaly with normal liver function and hepatic steatosis on ultrasound. no associated muscular atrophy. Diabetes is poorly balanced with 13.9% HbA1C complicated with diabetic retinopathy, with insulin requirements of 2 IU / kg / d. The lipidogram shows a hepertriglyceridemia at 16 mmol / L with a fasting opalescent serum. The thyroid status is normal.

Conclusions

Lipoatrophic diabetes is an exceptional entity that is difficult to manage because of the severity of insulin resistance and the lack of standardized therapeutic management. Our patient is a real case with difficulty equilibrium of diabetes despite the increase in doses of insulin, the only available therapy in Tunisia in this case. New therapies must be offered to these patients to balance diabetes and prevent complications.

Background and Aims

Poor glycemic control is type 1 diabetes mellitus patients a common issue. There is an increasing interest for addition of SGLT2 inhibitors to standard insulin treatment in these patients. This study was aimed at exploring the effects of empagliflozin on time in range parameters in overweight type 1 diabetes mellitus patients with poorly controlled glycaemia.

Methods

Ten type 1 diabetes mellitus patients (aged 45.5 ± 1.5 years; duration of diabetes 21.0 ± 3.6 years) received empagliflozin 25 mg daily in addition to standard insulin pump therapy. The continuous glucose monitoring data were analyzed at inclusion and after 12 weeks of treatment with empagliflozin. Several several parameters were determined: time above range (TAR; % of readings >10.1 mmol/L), time below range (TBR; % of readings <3.8 mmol/L) and time in range (TIR; % of reading 3.9-10.0 mmol/L). Paired sample t-test was used for statistical analysis.

Results

The addition of empagliflozin to standard insulin treatment significantly increased the TIR, for up to 1.6-fold, and significantly decreased TAR, for up to 1.2-fold, compared to initial values (both P<0.01). TBR remained unchanged during the study course. HbA1c decreased during treatment with empagliflozin from 7.9 ± 0.2% to 7.1 ± 0.1%. Additionally, a lower glycemic variability was observed.

Conclusions

The addition of empagliflozin to the standard insulin treatment improved glycemic control according to HbA1c and increased time in range in overweight type 1 diabetes mellitus with poorly controlled glycemia. These results emphasize the promising role of SGLT2 inhibitors in type 1 diabetes mellitus patients.

Background and Aims

Using present formulation strategies, insulin and pramlintide are unstable if mixed, and require separate administrations. The disparate pharmacokinetics of insulin and pramlintide following separate subcutaneous administrations does not mimic secretion from the beta-cells and inhibits their potential synergistic effects. Designer excipients that exhibit host-guest supramolecular interactions with protein drugs have potential to improve formulation stability of biologic therapeutics and allow for unprecedented formulation strategies. Here we develop an excipient strategy for simultaneous supramolecular PEGylation of insulin and pramlintide to generate a stable insulin-pramlintide co-formulation that more closely mimics endogenous secretion.

Methods

Protein stability when formulated with curcurbit[7]uril-poly(ethylene glycol) (CB[7]-PEG) was determined using a transmittance assay in order to detect the formation of aggregates that scatter light over time. The formulation pharmacokinetics and pharmacodynamics were evaluated in diabetic rat and pig models. Blood glucose levels are monitored and ELISA is used to measure the pharmacokinetics of the two hormones.

Results

CB[7]-PEG enables stable co-formulation of insulin and pramlintide for over 100 hours under stressed aging conditions where commercial formulations of insulin analogues exhibit only 10 hours of stability. Using diabetic rat and pig models, we demonstrate that co-formulation with CB[7]-PEG modifies the pharmacokinetics of both insulin and pramlintide, increasing the overlap between the time-frame of action of the two hormones, thus mimicking endogenous secretion and restoring meal-time glucagon suppression.

Conclusions

This insulin-pramlintide co-formulation more closely mimics endogenous co-secretion of insulin and amylin from the beta-cells and shows promise as a single administration therapy that could reduce patient burden and enhance diabetes management.

Background and Aims

People have been raised to think that there is a pharmacological cure for everything including chronic diseases such as diabetes which is so complex and damages so many bodily processes. It is for the same reason that others think that it is highly unlikely that such a medical cure will ever be found, and that if such a medicine be found, it would most likely cause other problems that could be even worse. Therefore, this paper will demonstrate how Strategic Poverty Alleviation Systems-SPAS has reinvented traditional foods and ancient/traditional medicinal resources such as organic grain amaranth and traditional healthcare systems and knowledge institutions as to engineer a paradigm shift to move healthcare systems for diabetes from management treatment to curative therapies status.

Methods

Trained communities grow grain amaranth plant genetic resources for food/nutrition and income and SPAS buys part of the surplus to use in making grain amaranth-based nutraceuticals for community members with diabetes and/or its complications with extremely promising results.

Results

These nutraceuticals have previously been given to people of all ages and gender with either type 1 or type 2 diabetes with spectacular results. For instance, within seven days diabetics taking these nutraceuticals are off all medications, and within fourteen days, the condition is completely reversed, together with its complications (e.g. blood glucose stabilizes around 4-6mmol/L permanently).

Conclusions

Substantial attitude shift will be needed as to decolonize the minds and spirit of communities as SPAS model leads the way in moving healthcare systems for diabetes from management treatment to curative therapies.

Background and Aims

Pramlintide, as an adjunct to insulin, improves postprandial blood glucose (ppBG) through delaying gastric emptying, reducing glucagon secretion, and promoting satiety. ADO09 is a co-formulation of pramlintide and a prandial insulin analog stable at pH 4. This double-blind, double-dummy, randomised, cross-over trial compared ADO09 with insulin lispro (LIS) and the separate injections of human insulin and pramlintide (Ins&Pram) in 24 patients with T1D.

Methods

At three dosing visits, participants received ADO09, Ins&Pram and LIS immediately before eating a standardised mixed meal (618 kcal, 53% carbohydrate, 19% protein, 26% fat, 2% fibers) and 1g paracetamol to evaluate the kinetics of gastric emptying. The insulin dose was 7.5 U and the pramlintide dose 45 µg.

Results

Compared with LIS, ADO09 reduced ppBG excursions by more than 95% over the first hour (p<0.0001), by 85% over 2h (p<0.0001) and 41% over 4h (p=0.0052) (Figure). With ADO09, gastric emptying was significantly slower than with LIS (Tmax_paracetamol 2.30±1.49 h vs 0.76±0.73 h, p<0.0001); and endogenous glucagon secretion was inhibited compared to LIS (deltaAUC_glucagon_0-2h 4.2±2.8 vs 11.8±6.2 pmol*h/L, p<0.0001). The effects of ADO09 and Ins&Pram were similar. All treatments were well tolerated and both adverse events (3 with ADO09, 2 with Ins&Pram) and hypoglycaemic events (2 each with ADO09 and Ins&Pram) were rare during the meal test procedures.

Conclusions

ADO09 was well tolerated, had similar effects on gastric emptying and endogenous glucagon secretion as separate injections of Ins&Pram and markedly reduced ppBG compared to LIS. These positive results warrant further investigations with ADO09 for the treatment of T1D.

Background and Aims

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in society, yet few drugs are available that specifically target this disease. Glucagon-like peptide-1 (GLP-1) mimetics were shown to alleviate pathology of non-alcoholic steatohepatitis (NASH), but the underlying mechanism is unknown. Here we aimed to identify mediators of inflammation in the context of NAFLD/NASH and investigate whether they can be targeted by dulaglutide.

Methods

Mice were fed with a diet (SSD) containing high amounts of fat, fructose and cholesterol to induce NASH. Histology was used to quantify liver pathology in animals. Genetically modified mice were used to demonstrate the specific role of immunological mediators in development of pathology. Animals were injected once weekly with dulaglutide or vector control to measure its impact on development of liver fibrosis and inflammation.

Results

SSD-diet induced all stages of NAFLD/NASH, including fibrosis. SSD induced a strong increase of IL-17 producing γδ T cells in liver. δ^-/- mice lacking γδ T cells, or animals with hepatocyte-specific deficiency for the IL-17 receptor showed a strong reduction in liver inflammation and fibrosis. We found that γδ T cells in liver expressed the receptor for GLP-1. Treatment of SSD-fed animals with dulaglutide impaired γδ T cell activation in liver and reduced fibrosis.

Conclusions

Hepatic stress in liver in the context of NAFLD activates γδ T cells. These cells start producing IL-17, which drives hepatic inflammation and fibrosis. Dulaglutide appears to impair γδ T cell activation and initiation of liver inflammation in the context of NAFLD/NASH.

Background and Aims

The use of natural products as a means of treatment for diabetes is currently gaining momentum in Nigeria.Hence this study was aimed at investigating the hypoglycaemic and antioxidant properties of Citrullus lanatus(watermelon)seeds and Moringa oleifera leaves in Alloxan-induced diabetic Wistar rats.A total of thirty rats were divided into six groups of 5 rats each.At the end of the experiment,rats were fasted overnight and blood samples were collected under chloroform anaesthesia for estimation of fasting blood glucose,antioxidant vitaminsA,C,E and fasting lipid profile using standard techniques.

Methods

Total of thirty rats were divided into six groups of 5 rats each.At the end of the experiment,rats were fasted overnight and blood samples were collected under chloroform anaesthesia for estimation of fasting blood glucose,antioxidant vitaminsA,C,E and fasting lipid profile using standard techniques.

Results

The results indicated a significant increase(p<0.05)in blood glucose and a significant decrease(p<0.05)in antioxidant vitamins in diabetic rats compared to non diabetic control.All the rats treated with ethanolic leaf extract of M.oleifera and C.lanatus seeds recorded a significant decrease in glucose level after 14days.Diabetic rats treated with both plants extract recorded a significant increase (P<0.05)in serum antioxidant vitamins.However, vitaminE was not significantly(P>0.05)increased in 200mg Moringa compared to the diabetic control.There were no significant differences (p>0.05)in the lipid profile parameters between the non diabetic control and diabetic group. However,LDL was significantly lower(p<0.05) while HDL was significantly higher(p<0.05)in non diabetic group than the diabetic control group.

Conclusions

These findings indicate that C.lanatus seed and M.oleifera leaves extracts possess hypoglycaemic and antioxidant properties.

Background and Aims

World is moving toward herbal remedies due to the side effects associated with the synthetic drugs utilized in the treatment of diabetes and its complications. The main objective of this study was to highlight the protective effect of Bauhinia variegata (BV) against streptozotocin (STZ) induced diabetic neuropathy and neurodegeneration (DNN).

Methods

Behavioral, biochemical, functional and structural biomarker assessment were done in STZ induced diabetic rats, further treated for 28 days with two dose levels of BV (200 mg/kg and 400 mg/kg).

Results

BV treated diabetic rats showed marked improvement in tail flick latency, pain threshold, locomotion and fall latency period. A significant reduction in glycosylated haemoglobin and blood glucose level was observed by BV in diabetic rats. Greater Antioxidant power of BV showed a rise in Super oxide dismutase, Catalase content and reduced oxidative stress by reducing serum nitrite and lipid peroxidation level; a significant reduction of C-reactive protein and decreased calcium (Ca⁺⁺) content of tissues were observed in diabetic rats which proves antiinflammatory and protective potential of BV. Marked protection was observed in diabetic hippocampal region of brain and sciatic nerve tissues when treated by BV. Antioxidant potential of BV revealed presence of high polar compounds observed in thin layer chromatography (TLC).

Conclusions

Present study strongly suggest the protective effect of Bauhinia variegata in diabetic rats by improving behavioral, biochemical, structural aspects of DNN.

Background and Aims

Semaglutide is a glucagon-like peptide-1 analogue formulated as a once-weekly subcutaneous (s.c.) injection and once-daily oral tablet for type 2 diabetes. Lower bioavailability following oral administration results in more variable semaglutide plasma concentrations versus s.c. administration. Effects of administration route on semaglutide efficacy and gastrointestinal tolerability were investigated.

Methods

Population pharmacokinetic data were compared from four 30-week trials (SUSTAIN 1–3, SUSTAIN-Japan) of once-weekly s.c. semaglutide (0.5, 1.0 mg; N=1552) and six 26-week trials (PIONEER 1–3, 5, 8, 9) of once-daily oral semaglutide (3, 7, 14 mg; N=3003). Differences in baseline HbA_1c, trial population, diabetes duration, race, ethnicity and sex between populations were balanced by propensity score matching. Exposure–response relationships were investigated for changes from baseline in HbA_1c and body weight, and proportion of subjects reporting nausea or vomiting during treatment.

Results

SUSTAIN and PIONEER populations were fairly similar. The exposure range was wider following oral versus s.c. dosing, but with considerable overlap between oral semaglutide (7 and 14 mg) and s.c. semaglutide (0.5 and 1.0 mg), indicating similar exposure levels. HbA_1c and weight reductions, and proportions of subjects reporting nausea or vomiting, were greater with increasing semaglutide exposure (Figure). The main covariate for glycaemic effect was baseline HbA_1c. Exposure–response relationships were consistent across the SUSTAIN and PIONEER datasets, and even more consistent when using propensity-matched data.

Conclusions

Exposure–response relationships for oral and s.c. semaglutide efficacy and tolerability were similar; the greater variability in semaglutide plasma concentrations following oral administration does not impact response.

Background and Aims

This work was designed to study dynamics of the symptoms of chronic painful form of diabetic polyneuropathy under the influence of the short-term treatment with alpha-lipoic acid (Tiogamma) and to identify the predictors of its effectiveness.

Methods

Was done analysis of treatment with alpha-lipoic acid (Tiogamma) for the diabetic polyneuropathy patients with chronic pain. Were studied 135 diabetic polyneuropathy patients with chronic pain (females-69%, males-31%; age - 56,9±11,8, duration of diabetus mellitus 15,8±9,5 years). Range of HbA1c was 8,4±2,3. Was studied dynamics of symptoms. Lipoic acid (Tiogamma) was administered by means of 10 infusions dosed 600 mg each. In order to determine the sensitivity and severity of sensorimotor polyneuropathy, a standard neurological examination was performed with the calculation of the severity of sensory and motor deficits according to the NIS-LL scale. The strength of neuropathic sensations was evaluated by a visual analogue scale (VAS). Treatment was considered effective, when the intensity of symptoms and pain was reduced by 50% or more.

Results

Initially, the average intensity of neuropathic symptoms according to VAS was 5.5 ± 2.6 points. After treatment-3,8±2,1 points. In 55% of patients the treatment was effective. The greatest effect of Tiogamma was noted for seizures, aching pains, tingling, burning and shooting pains. Dynamics of allodynia, hyperalgesia, and negative symptoms was insignificant.

Conclusions

We were able to show the uneven dynamics of different neuropathic sensations by the using Tiogamma.

Background and Aims

A novel ready-to-use liquid stable glucagon rescue pen (GRP; Xeris Pharmaceuticals), was evaluated for preparation time and relief of symptoms during rescue treatment of severe hypoglycemia.

Methods

A Phase 3 non-inferiority, randomized, controlled, single-blind, crossover clinical trial enrolled 132 adults with T1D to compare subcutaneous 1 mg doses of GRP versus powdered glucagon (GHK; Novo Nordisk) to treat insulin-induced severe hypoglycemia. Drug preparation time by trained providers was recorded, and assessments of the overall sensation of hypoglycemia were performed at each treatment visit.

Results

Criteria for non-inferiority were achieved, and all subjects achieved successful plasma glucose recovery. Mean drug preparation time for GRP was significantly faster than GHK (0.79±0.53 minutes, 1.76±0.68 minutes, p<0.001). Subjects administered GRP experienced comparable time to resolution of the overall feeling of hypoglycemia, compared to GHK (15.69±7.43 minutes, 15.32±8.48 minutes, p=0.91). The overall incidence of adverse events (AEs) was comparable in both groups; the most commonly reported AEs were mild to moderate nausea (GRP 42.5%, GHK 44.7%) and vomiting (GRP 12.6%, GHK 13.8%). No SAEs occurred related to GRP.

Conclusions

Prompt neurologic symptom relief is critical in the rescue from severe hypoglycemic emergencies. From decision to treat, GRP resulted in faster delivery of a full glucagon dose and achieved comparable relief from the sensation of hypoglycemia during insulin-induced severe hypoglycemia. GRP achieved successful plasma glucose recovery in a reliable manner, was safe and well tolerated, and had an incidence of nausea and vomiting comparable to GHK. GRP is a viable alternative to currently available GHK.

Background and Aims

Parenteral administration of therapeutic peptides can be associated with generation of anti-drug antibodies (ADAs). The antibodies can be neutralising or non-neutralising, which is of importance for drug safety and efficacy for indications where the peptide is to be administered repeatedly. A special risk for analogues of human peptides is cross reactivity towards the endogenous peptide.

Methods

In the ADA Phase 3 trial, the immunogenicity of dasiglucagon (0.6 mg) was tested. The reference product was GlucaGen® (1 mg). Patients were randomly assigned in a 1:1 ratio to receive 3 SC injections of either dasiglucagon or GlucaGen®, with 1 week between doses. Blood samples for ADA analysis were taken before each of the three doses and 35, 60 and 104 days after the first dose. In total 111 T1DM patients received at least one dose and 102 patients completed all three doses.

Results

The primary endpoint was the overall ADA incidence. No patient had any confirmed treatment-induced or treatment-boosted ADA response at any measuring time after dosing. Nausea and vomiting were the most commonly reported IMP-related AEs, reported with similar frequencies for dasiglucagon and GlucaGen® (nausea: 46% and 43%, vomiting: 21% and 15%, respectively). There were no injection site reactions after dasiglucagon administration, whereas eight injection site reactions in 6 patients were noted in the GlucaGen® group.

Conclusions

In conclusion, dasiglucagon had a low potential for generation of ADAs. The low potential for generation of ADA’s and low potential for injection site reactions are of particular importance for the chronic indications pursued with dasiglucagon.

Background and Aims

Severe hypoglycemia is a feared complication of insulin therapy and requires urgent assistance. Dasiglucagon is a peptide analog of human glucagon, stable in aqueous solution, in development for treatment of severe hypoglycemia via a ready-to-use auto-injector.

Methods

In this pivotal Phase 3 trial, the clinical efficacy and safety of 0.6 mg dasiglucagon were compared to placebo and with reference to GlucaGen®. In total, 168 patients with T1D were randomized (2:1:1) and dosed following induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery, defined as first PG increase ≥20 mg/dL after treatment initiation.

Results

Data showed dasiglucagon 0.6mg rapidly increased PG. The median time to recovery was 10 min for dasiglucagon and 12 and 40 min for GlucaGen® and placebo, respectively. In the dasiglucagon arm, 65% of patients had recovered within 10 min vs 49% of patients receiving GlucaGen®. Similarly after 15 min, 99% of patients treated with dasiglucagon had recovered vs 95% of patients treated with GlucaGen®. Nausea and vomiting were reported with similar frequencies for dasiglucagon and GlucaGen® (nausea: 55% and 53%, vomiting: 23% and 19%, respectively). Injection site reactions 30 minutes post dose were reported in 2%, 7% and 5% of patients in the dasiglucagon, GlucaGen® and placebo groups, respectively.

Conclusions

In conclusion, dasiglucagon 0.6mg was demonstrated to be a fast and effective treatment for severe hypoglycemia. The stability of dasiglucagon in aqueous formulation enables further development of dasiglucagon as a treatment option in the entire spectrum of mild, moderate and severe hypoglycemia.

Background and Aims

Diabetes and other metabolic abnormalities including high triglycerides (TG) are commonly seen comorbid conditions in patients having nonalcoholic fatty liver disease (NAFLD). There is no approved pharmacotherapy for NAFLD and lifestyle therapy plays a major role. Saroglitazar, the world’s first approved dual PPAR α/γ agonist, is approved in India for the treatment of diabetic dyslipidemia. The objective of this case series analysis was to evaluate the safety and effectiveness of saroglitazar 4mg once daily in reducing liver stiffness in patients having diabetic dyslipidemia associated NAFLD

Methods

In this retrospective case series analysis, we identified 10 patients with diabetic dyslipidemia (type 2 diabetes and triglycerides >200 mg/dL at baseline) and NAFLD who were treated with saroglitazar 4mg once daily and the follow-up data were available for 9 months after saroglitazar treatment. At baseline, all patients were on stable antidiabetic and statin therapy. Liver stiffness was measured by using 2D shear wave elastography at baseline and at 9 months follow-up.

Results

We analysed a total of 10 patients (male: female 7:3) with mean baseline HbA1c and TG values were 7.8% and 298.2 mg/dL respectively. The mean baseline SWV value 1.837±0.0691 m/s was reduced significantly to 1.645±0.0844 m/s at 9 month follow-up after saroglitazar treatment. At 9 month follow-up after saroglitazar, HbA1c level was significantly reduced from 7.8±0.343% to 6.9±0.33% (P<0.0001). Serum TG was also significantly reduced from 298.2±35.75 mg/dL to 202.4±13.19 mg/dL (P<0.0001) at 9 month follow-up.

Conclusions

In this study saroglitazar significantly improved liver stiffness along with reduction in liver enzymes and TG values.

Background and Aims

Aim and Objective :

To evaluate the effect of Comprehensive Diabetes Care (CDC) in pre-obese DM patients

To evaluate the effect of CDC on HBa1C, weight

Methods

Methodology :

The study was carried out on 23 out-patient selected from departments (OPDs) at Madhavbaug clinics, identified between April 2017 to July 2017.

Data of only those patients were included who had received the scheduled 6 sitting of CDC in a span of 90 days. In this study, the variables [HbA1c, body weight, body mass index (BMI), dependency on medications] were assessed on day 1 and day 90 of Comprehensive Diabetes Care CDC.

The patients were already on prescribed concomitant medications. CDC Program consisting of panchkarma procedures namely Whole Body Snehan (external oleation) and Swedan (passive heat therapy) with PRDA was given to the patients

Results

Result :

Out of the 23 patients, majority (15) were males.

The mean HbA1c measured at day 90 was significantly lesser than that on day 1 (7.12±1.07 vs 8.53±0.89, p<0.001).

The mean weight of the patients was reduced significantly on day 90 when compared to day 1. (62.40±7.82 vs 67.17±7.44, p<0.001).

The mean BMI was significantly reduced on day 90 when compared to the baseline (24.75±2.18 vs 27.0±1.41, p<0.001).

The abdominal girth was significantly reduced on day 90 compared to baseline (87.69±7.89 vs 93.05±7.90,p<0.001). Dependency on concomitant medicines was also reduced.

Conclusions

madhavbaug cdc program helps to reduce dowm Hba1c naturally

Background and Aims

Adequate management of refractory pain developed in chronic diabetic neuropathic pain is one of the most difficult and debatable problem in the modern palliative care. The goal of our study was management of chronic diabetic neuropathic pain.

Methods

An experimental study on refractory pain was conducted in a number of palliative clinics on 81 randomly selected patients with diabetic neuralgia, 59% of which participated in the previous double-blind randomized controlled trial in which Pregabalin was used in different dosage regimen. Short-Form McGill Pain Ques–tionnaire (SF-MPQ) along with VAS were employed. The patients were enrolled based on the screening criteria – chronic pain intensity minimum 40 mm by VAS. 90% of the study subjects were classified as refractory to Gabapentin and Tricyclic Antidepressants. 63% suffered with severe pain. Pregabalin was used in a fixed dose of 150-600 mg/day, that was changing by necessity.

Results

Study findings showed effectiveness of Pregabalin in the treatment of neuropathic refractory pain. It was more effective, then combination of Gabapentin and Tricyclic Antidepressants. Effectiveness of Pregabalin was similar in patients, receiving and non-receiving concomitant gabapentin. In 1/3 of patients pain was relieved by > 50% and it was stable during 17 month-observation period. After 17 month-duration treatment with Pregabalin proportion of patients with severe pain significantly reduced (from 63% to 23%).

Conclusions

Based on our study effectiveness of Pregabalin in the treatment of neuropathic refractory pain is reliably high

Background and Aims

A previously healthy girl was diagnosed with antibody-negative DM at the age of 5 years. New generation sequencing showed a double heterozygous mutation of the WFS1 gene. Comorbidity screening showed initial optic nerve involvement at magnetic resonance imagine (MRI) and optical coherence tomography (OCT) evaluation.

Methods

Liraglutide (LG) was identified as the most promising disease-modifying candidate with the safest pediatric profile and was started at age 8 years.

Results

After 6 months treatment with LG 1.2 mg/day:basal and peak Cpeptide (ng/mL) at the mixed meal tolerance test improved from 0.14 (blood glucose 109 mg/dL) and 0.31 (blood glucose 211 mg/dL) to 0.19 (blood glucose 95 mg/dL) and 0.4 (blood glucose 93 mg/dL) respectively. Glucose time in range improved from 66% (time in hypoglycemia 2%) to 78% (time in hypoglycemia < 1%). Daily insulin needs reduced from 0.4U/Kg to 0.3U/Kg. OCT did not show significant progression in retinal nerve fiber layer (right 71-74 micron, left 68-68 micron) and ganglion cell-inner plexiform layer thickness (right 70-68 micron, left 69-69 micron). No significant gastrointestinal symptoms were reported.

Conclusions

GLP-1R agonists are potential drugs in WS because of their role in decreasing ER stress in both -cells and neurons. Only one LG-treated WS patient has been reported in literature. This is, to our knowledge, the first reported pediatric cases of WS treated with LG with apparent improvement in C-peptide and stabilisation of OCT parameters at 6 months and no adverse events. Longer and larger population RCT studies are warranted prior to it becoming used in routine care.

Background and Aims

Nasal glucagon (NG), a ready-to-use drug-device combination for the treatment of severe hypoglycemia (SH), contains 3 mg glucagon dry powder that is absorbed through the nasal mucosa. A clinical trial (CT) and a real-world study (RWS) examined efficacy, effectiveness, and tolerability of NG in reversing hypoglycemia in children with type 1 diabetes (T1D).

Methods

Post hoc analyses were performed using data from participants, 4 to 17 years old, whose insulin-induced nadir blood glucose (BG) reached ≤70 mg/dL (CT) or whose baseline BG reached <54 mg/dL (RWS). Treatment success was defined as ≥25 mg/dL BG increase from nadir within 30 min of glucagon treatment (CT) or return to normal status from neuroglycopenic symptoms within 30 min of NG treatment (RWS).

Results

In the CT, NG (n=16) and injectable glucagon (IG) (n=12) achieved treatment success in 100% of participants, in mean times (excluding glucagon preparation) of 14 min and 13 min, respectively. Nadir BG was 63 mg/dL for NG and 62 mg/dL for IG. Incidences of NG and IG adverse events (AE) were similar for nausea and vomiting; headache and nasal symptoms occurred more frequently with NG than IG. In the RWS, NG resolved all 17 events (mean baseline BG=49 mg/dL) within 30 min (mean time=14 min). NG administration was considered easy or very easy during 16 of 17 events. The most common reported adverse symptoms were nasal discomfort, headache and watering eyes.

Conclusions

NG is an effective, well-tolerated and easy-to-use treatment for SH in children with T1D.

Background and Aims

The search for new effective ways to treat diabetes is one of the most important problems of medicine. The purpose of study was to determine the levels of lipid peroxidation, oxidative modification of proteins, the content of nitric oxide, Schiff bases and the state of the thiol-disulfide system in the mitochondrial fraction and the total homogenate of the tissue of the liver of the white rat in alloxan diabetes and treatment with taurine.

Methods

The study was conducted on outbred white rats. Alloxan diabetes is caused by the administration of 40 mg / kg of alloxan. Lipid peroxidation was determined by the method of Barkovsky EV. Oxidative modification of proteins was determined by the method of Dubinin et al. The amount of protein was determined according to Lowry. Glutathione peroxidase activity was determined by the reduction of hydrogen peroxide and lipid hydroperoxide in the presence of GSH. The optical density of the Schiff bases was determined at a wavelength of 400 nm.

Results

Studies have shown that alloxan diabetes is characterized by the activation of free radical oxidation processes, as well as a decrease in glutathione content and a decrease in the activity of glutathione-containing enzymes. Introduction of taurine leads to a decrease in the content of lipid peroxidation products, partial normalization of the oxidative modification of proteins and Schiff bases in the common liver homogenate of rats with alloxan diabetes.

Conclusions

Thus, we can conclude that the administration of taurine to rats with alloxan diabetes leads to the normalization of oxidative processes.