Basal insulin represents an essential tool in the treatment of both type 1 and type 2 diabetes mellitus. The development of insulin analogues has improved the possibilities of diabetes treatment. Despite significant progress in understanding the physiology, chemistry, kinetics and action of insulin, currently available basal insulin products do not optimally mimic the endogenous profile of insulin. Although basal insulin analogues have some advantages over neutral protamine Hagedorn insulin in diabetes treatment, hypoglycaemia remains the main problem in the achievement of optimal glycaemic control in most patients with diabetes. These unmet clinical needs have stimulated the development of new basal insulin analogues with improved pharmacological profiles. This article reviews the specific characteristics of new long-acting insulin analogues to try and understand their benefits and limitations in the improvement of diabetes management and their possibilities in physiologic and safe insulin replacement.

The morbidity and mortality associated with type 2 diabetes have increased over recent years. The causes of death include cardiovascular disease, cancer, infection, kidney disease and diabetic coma. Risk factors for death are a sedentary lifestyle, obesity, smoking, sex, age, duration and severity of diabetes, macro- and microvascular complications and hyper- and hypoglycaemic states. Adequate glycemic control and moderate exercise along with the use of antiplatelet agents (e.g. aspirin), statins, antihypertensives and metformin can reduce mortality. Intensive glucose control was associated with an increased risk of severe hypoglycaemia and death, and surgical intervention increased the risk of death.

Background.

The main aims of the conservative treatment of metabolic obesity (MО) are weight loss and the prevention of type 2 diabetes. Incretin-based drugs are considered to be effective and safe and stimulate insulin secretion via the β-cells of the pancreas, and are widely used to restore impaired glucose tolerance. Bariatric surgery not only significantly reduces BMI but also normalises carbohydrate metabolism in patients with MО over a short period after the operation by increasing the secretion of endogenous incretins.

Aim.

To investigate hormone secretion in the gastroduodenal zone in patients with MО after Roux-en-Y gastric bypass before and after a test meal.

Material and methods.

We studied the plasma levels of insulin, C-peptide, glucagon, ghrelin and incretins (GIP and GLP-1) using flow fluorometry in 28 patients with MO (12 males and 16 females aged 29–63 years). Patients were divided into two groups: those who did not undergo gastric bypass surgeries and those after treatment (18 months).

Results.

We found a postprandial increase in the plasma GIP levels with respect to the baseline values in all subject groups, regardless of whether or not they had type 2 diabetes. A analysis of the levels of postprandial GLP-1 secretion revealed the existence of multidirectional dynamics of this indicator regardless of the presence of type 2 diabetes: an increase, decrease, or no difference in GLP-1 secretion was found compared to the measurements on an empty stomach.

Conclusions.

The postprandial GIP levels increased compared with baseline levels in all groups. The dynamics of the changes in the postprandial GLP-1 levels were multidirectional in patients with MО regardless of the presence of impaired glucose tolerance after Roux-en-Y gastric bypass. A positive correlation was observed between the plasma ghrelin levels and glucagon in all groups.

Despite the increase in the number of hypoglycemic agents, 35%–40% of patients with diabetes are unable to achieve adequate glycemic control. One of the reasons is the genetic heterogeneity of diabetes mellitus, requiring different treatment approaches; however, the individual metabolic features and sensitivity to drugs also affect the therapeutic effectiveness. The review presents the main results of pharmacogenetic research of several antidiabetic drugs: metformin, sulfonylurea, agonists of glucagon-like peptide-1 and thiazolidinediones.

In recent years, actively studied the effect of androgen deficiency on the cardiovascular system, including endothelial function. Genomic effects of testosterone caused by the length of CAG repeats polymorphism in the androgen receptor (AR) gene.

Aim.

To examine the association of the polymorphism in the AR gene and carbohydrate, lipid metabolism, endothelial function in men with type 2 diabetes.

Materials and methods.

We examined 88 men, aged 40-65 years (mean age 53±6,4years) with type 2 diabetes. All patients underwent the study of carbohydrate and lipid metabolism, the assessment of vasomotor endothelial function of the brachial artery by ultrasound sonography, were studied biochemical markers of endothelial dysfunction – ICAM-1, VCAM-1, p-selectin, e-selectin, resistin and number of CAG-repeats in the AR gene. Statistical analysis was performed using the application package SPSS 21,0 using regression analysis.

Results.

The number of CAG repeats had a significant positive regression to the level of total testosterone, a weak negative regression of the number of CAG repeats in the AR gene and lipid metabolism: triglycerides, LDL, atherogenic index. The assessment of the brachial artery ultrasonography revealed negative regression of the baseline brachial artery diameter and blood flow velocity in the endothelium-dependent vasodilation. The number of CAG repeats was significantly correlated with the levels of p-selectin and resistin. Thus, increasing the number of CAG repeats in the AR gene via a weakening of sensitivity to androgens leads to disruption of endothelial function in men with type 2 diabetes. Increasing the number of CAG repeats in the AR gene leads to deterioration of linear flow velocity during the test with reactive hyperemia with increasing production of p-selectin and resistin.

Conclusions.

The number of CAG repeats in the AR gene can be regarded as a predictor of the development and progression of cardiovascular lesions in men with type 2 diabetes.

Background.

Over the long disease course of diabetes mellitus (DM), with its demands in terms of everyday self-management of the disease, individual psychological characteristics may be associated with both emotional well-being (WB) and glycaemic control. The former includes various types of coping strategies (CSs) of the patients, which comprise the common ways for patients to overcome difficult situations.

Aim.

To study the relationships between CS and both glycaemic control and emotional WB in patients with Type 1 diabetes (T1D) and Type 2 diabetes (T2D) treated with insulin.

Materials and methods.

The study included 84 patients with T1D and 56 patients with insulin-treated T2D [age, 22.5 ± 3.3 and 61.0 ± 8.9 years; men/women, 29/55 and 11/45; duration of DM, 11.9 ± 5.36 and 11.6 ± 6.2 years and glycated haemoglobin (HbA1c), 9.1% ± 2.2% and 9.0% ± 1.4%, respectively]. The HbA1c levels were determined in all patients. The Strategic Approach to Coping Scale constructed by S. Hobfoll was used to study CS, and emotional WB was assessed based on the severity of anxiety and depression. Further, we used the State-Trait Anxiety Inventory developed by C.D. Spielberger and adapted by Y.L. Khanin and the Center for Epidemiologic Studies Depression Scale. Only Russian validated versions of the questionnaires were used in the study.

Results.

In both groups of patients, ‘Assertive (Persistent) Actions’ was positively associated with emotional WB. In patients with T2D, WB increases when using ‘Cautious Action’ and ‘Social Joining’. The deterioration of emotional WB was associated with ‘Aggressive Actions’ in both groups of patients. In patients with T1D, negative WB was also associated with ‘Avoidance’, while in patients with T2D, negative WB was associated with ‘Instinctive Actions’. In patients with T1D, ‘Instinctive Action’ was associated with higher HbA1c levels. In patients with T2D, ‘Cautious Action’, ‘Avoidance’ and ‘Antisocial Action’ were associated with lower HbA1c levels.

Conclusion.

In patients with T1D and T2D, CSs are associated with both emotional WB and glycaemic control. Emotional WB and lower HbA1c levels are associated with ‘Assertive Action’, ‘Cautious Action’, ‘Avoidance’ and ‘Asocial Action’. Negative WB and higher HbA1c levels are associated with ‘Aggressive Action’ and ‘Instinctive Action’.

Aim.

To study quality of life (QoL) and hypoglycaemic symptoms in patients with type 2 diabetes receiving intensive insulin therapy.

Materials and methods.

One thousand patients with type 2 diabetes receiving intensive insulin therapy for at least 6 months were enrolled in this multicenter observational study. The mean age of patients was 61.1 years (range, 29–84 years) and the male/female ratio was 265/735. All patients completed the SF-36® questionnaire and the Comprehensive Symptom Profile-Diabetes Mellitus Hypoglycemia Module. For group comparisons, we used unpaired t-tests or Mann–Whitney tests and general linear models. To compare categorical variables, the χ2 test and Fisher’s exact test were used.

Results.

The patients with type 2 diabetes receiving intensive insulin therapy demonstrated heterogeneity in terms of QoL. More than half of the patients had mild QoL impartment while nearly one third experienced significant QoL impairment. The following factors had the most pronounced negative impact on QoL: late diabetic complications, concomitant diseases, poor glycemic control and type of hypoglycaemia. QoL parameters were lower in patients with hypoglycaemic episodes than in those without (p <0.01), but in patients with mild hypoglycaemia it was similar to those without. The most pronounced disturbances in QoL occurred in patients with severe and nocturnal hypoglycaemia (p <0.05). The hypoglycaemic symptoms with the greatest burden on QoL were dizziness, morning weakness, eye problems, nightmares or crying out during sleep, distress, loss of energy and sleep disturbances. Correlation between the severity of fear of hypoglycaemia and QoL was also demonstrated. Higher the fear of hypoglycaemia, the more impaired was social functioning, mental health, vitality and general health.

Conclusion.

Assessment of QoL and hypoglycaemic symptoms in patients with type 2 diabetes receiving intensive insulin therapy reveals the need for a patient-centred approach in treatment and for a comprehensive evaluation of treatment outcomes.

Aim.

The aim of our cross-sectional study was to evaluate the nutrition (or diet) habits of people with type 2 diabetes mellitus (DM) in the urban population (45–69 years) of Novosibirsk.

Materials and methods.

We included 1,041 people with DM and 8,095 people without DM in this study. The nutrition data were obtained via a population survey using a questionnaire to assess the frequency of food consumption within the framework of HAPIEE, an international project.

Results.

The prevalence of DM was 11.4% in this study population. The nutrition intake analysis showed that carbohydrate consumption in both men and women with DM was significantly lower compared with that in those without DM, while fat and protein intake were significantly higher. In men with type 2 DM, the proportions of black bread, vegetables, dairy products and meat in the diet were significantly higher, while the proportions of white bread and sweets in the diet were significantly lower compared with their counterparts without DM. Women with DM also had significantly higher proportions of black bread, vegetables, dairy products, meat and fish in the diet and lower proportions of white bread, potatoes and sweets in the diet than the controls. The proportions of fruit, eggs and alcohol intake did not differ between the groups for both men and women. In men, there was also no difference in the proportions of potatoes, vegetables and fish intake between the groups.

Conclusion.

The diets of both patients with DM and the general population in Novosibirsk are not well balanced.

Aim.

To assess the relationship of glucose variability (GV) and renal function in patients with type 2 diabetes on basal-bolus insulin therapy.

Materials and methods.

We observed 101 females with type 2 diabetes, aged 47–79 years, with a glomerular filtration rate (GFR) >30 mL/min/1.73 m2. Insulin was combined with metformin in 45 of these women. The mean glucose and standard deviation, continuous overlapping net glucose action, lability index, J-index, low blood glucose index (LBGI), high blood glucose index (HBGI), M-value and mean absolute glucose (MAG) were calculated based on the results of blinded continuous glucose monitoring. The prevalence of episodes of low interstitial glucose (<3.9 and 2.8 mmol/L) of at least 20-min duration was estimated.

Results.

Patients with a GFR of 30–44 mL/min/1.73 m2 had significantly lower HBGI, J-index, MAG and M-value compared with those with better filtration (all p < 0.05); LBGI was not dependent on GFR. The GFR values were weakly and positively correlated with HBGI, J-index, M-value and MAG. Multiple regression analysis showed that GFR is an independent predictor of MAG (p = 0.04). No significant differences were found in the prevalence of episodes of low interstitial glucose between patients with different GFR ranges.

Conclusions.

GV parameters are related to renal function in type 2 diabetic women on basal-bolus insulin therapy. Patients with stage 3b chronic kidney disease have reduced GV, predominantly in the hyperglycaemic band, compared with those with better filtration.

Aim.

To evaluate the morphological and immunohistochemical features of granulation tissue formation in patients with diabetic foot syndrome.

Materials and methods.

We analysed the histological (light microscopy) and immunohistochemical (CD31, CD68, osteopontin, MMP-9 and TIMP-1) features of tissue repair processes in patients with diabetes mellitus. The study involved 63 patients with diabetic foot syndrome after surgical debridement.

Results.

We found severe intercellular oedema, poorly organised extracellular matrix, small amounts of fibroblast-like cells and expressed inflammatory infiltration, along with the presence of young granulation tissue. According to the results of the immunohistochemical studies, there were a moderate number of macrophages (immunopositive with antibodies to CD68), intense staining of MMP-9 and weak staining of TIMP-1 and osteopontin.

Conclusion.

According to the findings of the histological and immunohistochemical studies, tissue repair processes in patients with diabetes mellitus are decelerated.

Aim.

To evaluate the use of orthopaedic shoes in patients with diabetes with foot ulcers and/or previous minor amputations or Charcot arthropathy (CA) and factors influencing this use.

Patients and methods.

One hundred twenty-one patients with diabetes (55 men and 66 women; 36 in the inactive stage of CA) were included. A questionnaire based on footwear was used to evaluate patients’ compliance. Daily activity and the severity of the foot deformities were recorded. Further, foot geometry and forefoot and midfoot circumferences were measured.

Results.

Fifty-eight patients did not use orthopaedic shoes. Users and non-users did not differ in terms of gender and type of diabetes. The causes of refusal included ill-fitting shoes (56%), ugly appearance (11%), traumatisation with shoes (11%), inability to walk (5%) and other causes (17%). The percentages of patients in each category of deformity severity were mild (41.2%), moderate (37%) and severe (54%. Frequency of refusal of CA vs non-CA patients: 72.2% and 43.5%; with severe deformities,70.8% vs 34%; with moderate deformities, 83.3% vs 57.2% (p < 0.05 for all). In patients with CA, the only significant parameter was the difference in the circumference of the midfoot between the affected and non-affected foot; in CA users and non-users, this parameter was 1.93 ± 1.25 vs 0.70 ± 0.83 cm, respectively (р = 0.01).

Conclusions.

The high frequency of refusing to wear orthopaedic shoes is related to severe foot deformities and the inability to accommodate them in off-the-shelf footwear. Most of the patients used orthopaedic shoes for outdoor use, but the frequency of use was low. Shoe compliance did not depend on gender but increased with ageing, low levels of daily activity and in patients with severe deformities. Patients with CA are characterised with extremely low compliance. In this group, foot parameters and other objective parameters did not rely on footwear compliance.

The evidence for DPP-4 inhibitors effectiveness at the late stages of type 2 diabetes mellitus (T2DM) are still growing. This is particularly important for those patients who receive insulin without adequately glycemic control. This publication provides the overview of studies which demonstrate high efficacy of Vildagliptin in reducing the blood glucose level in patients with hight duration of T2DM and insulin therapy. DPP-4 inhibitors normalize basal and postprandial glucagon secretion with pancreas α-cells that helps to provide better glycemic control and to reduce a risk of hypoglycemia. Besides, there are very interesting data for Vildagliptin to reduce insulin requirement in T2DM patients in addition to HbA1clevel decrease.

Aim:

The aim of this study was to evaluate the efficacy and safety of the new ultra-long-acting insulin degludec (Tresiba®) in the treatment of type 2 diabetes in routine clinical practice.

Methods:

This primary health care clinical observational study included 20 insulin-naïve type 2 diabetic patients (mean age: 57.2 years, range: 54.4–61.5 years), who were inadequately controlled on maximum tolerated doses of oral antidiabetic drugs (OADs) and in whom baseline insulin therapy with ultra-long-acting insulin degludec was initiated. The duration of treatment was 6 months. The list of procedures met the ‘Standard of primary medical care in non-insulin-dependent diabetes mellitus’, as approved by the Ministry of Health of the Russian Federation (12.28.2012 №1581-n). Quality of life was assessed using the SF-36 questionnaire. All patients provided written consent before participating in the study.

Results:

In the outpatient setting, insulin degludec was well tolerated by all the patients. During the observational period, there were no events of symptomatic hypoglycaemia confirmed by self-measured plasma glucose (blood glucose level <3.9 mmol/l). At the end of the observational period, HbA1c, fasting plasma glucose level (FPG) and postprandial (2 h after a meal) plasma glucose level (PPG) had decreased. Despite the fact that most of the patients had poor baseline glycaemic control, after 6 months of degludec therapy, 45% of the participants achieved a target HbA1c of <7.0%, and 45% achieved a target HbA1c of <8.0%. Improved glycaemic control was associated with increased quality of life scores on both physical and mental health components.

Conclusion:

In this primary health care clinical observational study, the initiation of insulin degludec in type 2 diabetes patients with poor glycaemic control on OADs was associated with the achievement of effective glycaemic control. In addition, it had a good safety profile, and it improved quality of life scores and adherence to the treatment.

Aim.

To assess morphological changes of retinal layers and optical density of macular pigment in patients with diabetic macular edema (DME) for the diagnostic criterion of pathological process.

Materials and methods.

31 patients were divided in two groups. The first group (A) included 19 patients with DME (20 eyes), the second group (B) – 12 patients (20 eyes) without retinal pathology. Both groups were comparable with regard to age. Parameter estimation was conducted with the use of following methods: optical coherence tomography (OCT) of the macular area of the retina; fundus photography with the measurement of macular pigment optical density (MPOD); microperimetry.

Results.

OCT analysis showed that the inner nuclear and plexiform layers of retina were the most involved in pathological process and revealed significant differences in increase of mean retinal thickness in comparison with the control group. Analysis of MPOD revealed a significant reduction of all parameters in group A compared with the control group. On the basis of microperimetry of the central area of retina in group A light sensitivity indicators were reduced by an average of 9 dB and equaled 9.85 ± 0.09 dB. The analysis showed gross violations of retinal structure and distribution of optical density of macular pigment in patients with DME. Correlation analysis of retinal thickness, functional light sensitivity and optical density of macular pigment traced a strong connection (r = -0.93; p <0.05) between the indices of retinal thickness and MPOD.

Conclusions.

Diabetic macular edema showed a sharp decrease in optical density of macular pigment determined by deficiency of lutein and zeaxantin. A correlation between quantitative indicator of optical density of macular pigment and area of edema was established. Light sensitivity was significantly reduced in the central part of the retina.

Most of the questions regarding vascular and rheological regulation related to normal health and disorders of carbohydrate metabolism remain unclear, which is important in the pathogenesis of angiopathy. Consequently, in the literature, there is no information about the function of endothelial vasomotion during occlusion. The present study investigated early postmenopausal women, when clinical, metabolic, and hemodynamic disturbances often manifest.

Aim.

To study the association between clinical and biochemical indicators of endothelial microcirculation in naturally postmenopausal women with different carbohydrate metabolism statuses.

Materials and methods.

We surveyed 94 postmenopausal women who were divided into three groups based on their carbohydrate metabolism status: group 1, type 2 diabetes mellitus (n = 52); group 2, prediabetes (n = 16); group 3, normoglycemia (n = 26). The following indicators were assessed: lipid profiles and anthropometric fasting plasma glucose, glycated hemoglobin, vascular endothelial growth factor (VEGF), and endothelin-1 levels. Microcirculation was evaluated by laser Doppler flowmetry (LDF). Statistical analysis was performed using SPSS software (version 17.0).

Results.

LDF parameters in group 3 were significantly different from group 1 during occlusion and reperfusion and also from group 2 in basal blood flow. During occlusion, the frequency of microcirculation oscillation was higher in group 1, whereas the amplitude of oxygen saturation oscillation was lower in group 3 than those in group 2. VraEr and Vra/mEr indicators during reperfusion in group 1 and VrfEf during basal blood flow in group 2 were higher than those in group 3; Vr parameters reflect the contribution of fluctuations in the relative erythrocyte volume in the probed area of skin to the modulation of vascular tone. In group 1, occlusal LDF indicators correlated with waist circumference, whereas VEGF, lipid profile parameters, and reperfusion parameters, VraEr correlated with systolic blood pressure and lipid profile. In group 2, VrfEf inversely correlated with VEGF levels, and in group 3, the frequency of microcirculation oscillation inversely correlated with endothelin-1 levels.

Conclusions.

We revealed the associations of metabolic, anthropometric, and hemodynamic factors as well as biochemical markers of endothelial dysfunction with microcirculation parameters in various modes of endothelial activity (basal, occlusion, and reperfusion) in postmenopausal women according to their carbohydrate metabolism status; we also describe the effect of age on microvasculature vasomotion.

Aim.

The haemodynamics of patients with diabetes mellitus 2 during acute ischaemic stroke and their connection with the recovery of neurological deficit has been inadequately studied.

Materials and Methods.

We studied the blood pressure dynamics of 183 patients with mild-to-moderate acute ischaemic stroke receiving antihypertensive therapy, depending on whether or not they had type 2 diabetes mellitus.

Results.

In patients with diabetes, high blood pressure persisted during the first week, mainly because of the diastolic index, and they had a more rapid decline in blood pressure in the second week than those without diabetes. However, reaching the target blood pressure of <160/100 mmHg was faster in patients with diabetes, regardless of the intensity of antihypertensive therapy. Although diabetes significantly correlated with the efficiency of recovery of neurological deficit, it also showed a tendency to frequent functional impairment in patients with diabetes than those without diabetes.

Conclusions.

The results suggest that patients with diabetes and hypertension require less aggressive treatment, particularly in the second week of hospitalization. This may affect the efficiency of recovery of functional deficits. Further study of blood pressure dynamics and their relation to functional recovery of neurological deficit is required during the acute period after an ischaemic stroke in patients with diabetes.

The results from the analysis of the ADVANCE trial and post-intervention program ADVANCE-ON are presented in this article. These studies are dedicated to study the effect of intensive glycemic control on the incidence of micro- and macrovascular events in patients with type 2 diabetes mellitus and evaluation of long-term results of intensive glycemic control. We discuss the progress of views on the impact of glycemic control on the development of cardiovascular complications. According to the analysis of the research results, gliclazide MR is safe in patients with type 2 diabetes at high risk for cardiovascular complications.

Incretin hormones are important for normal pancreatic islet function and glucose homeostasis. Sensitivity to glucose of the α- and β-cells of the pancreas is diminished in type 2 diabetes mellitus (T2DM), leading to impaired insulin secretion, insulin resistance due to elevated glucagon levels in hyperglycaemia and impaired glucagon counterregulation in hypoglycaemia. In addition, T2DM is associated with increased lipotoxicity-induced insulin resistance. This article is a comprehensive review of the safety and efficacy of vildagliptin in patients with T2DM and evaluates the extra-pancreatic effects of incretin-based therapies. Clinical evidence has proven that vildagliptin effectively decreases HbA1c with a low risk of hypoglycaemia and is weight neutral. Vildagliptin also suppresses postprandial triglyceride (TG)-rich lipoprotein levels after ingestion of fat-rich meals and reduces fasting lipolysis, suggesting inhibition of fat absorption and reduced TG stores in non-fat tissues.

Aims.

Insulin degludec (IDeg) is a novel insulin analogue that, following subcutaneous injection, forms soluble multihexamers, resulting in an ultra-long duration of action, which is two-fold longer than that of insulin glargine (IGlar). We present data from Russian cohorts of two multinational, open-label, treat-to-target phase 3 trials that investigated the efficacy and safety of IDeg and IGlar administered once daily.

Materials and methods.

The BEGIN Basal–Bolus Type 1 trial was a 52-week study comparing IDeg (n = 45) to IGlar (n = 16), both 100 U/mL, and in combination with insulin aspart in patients with type 1 diabetes (T1D). The BEGIN LOW VOLUME trial compared IDeg (200 U/mL; n = 27) to IGlar (100 U/mL; n = 28) over 26 weeks in insulin-naïve patients with type 2 diabetes (T2D) inadequately controlled with oral antidiabetic drugs. The primary outcome of both studies was the non-inferiority of IDeg to IGlar, as assessed by HbA1c level reduction at the trial end.

Results.

In patients with T1D, HbA1c level reductions at the trial end were 0.42% (IDeg) and 0.22% (IGlar). The rates of confirmed hypoglycaemia (plasma glucose level < 3.1 mmol/L or severe) were lower in IDeg than in IGlar [17.83 vs. 22.87 events/patient/year exposure (PYE), respectively]. The rates of nocturnal-confirmed hypoglycaemia were lower for IDeg than for IGlar (2.24 vs. 4.77 events/PYE, respectively). Severe episodes occurred in >10% of patients in both treatment groups, with rates per PYE of 0.12 (IDeg) and 0.06 (IGlar). In patients with T2D, HbA1c levels decreased by 1.17% (IDeg) and 1.26% (IGlar) at the trial end. The rates of confirmed hypoglycaemia were comparable in IDeg and IGlar (0.52 vs. 0.44 events/PYE, respectively). The rates of nocturnal-confirmed hypoglycaemia were lower for IDeg than for IGlar (0.18 vs. 0.28 events/PYE, respectively). No severe episode occurred in either treatment group. In both studies, IDeg was well tolerated with no difference in safety between the two analogues investigated.

Conclusions.

In both T1D and T2D, IDeg provided similar glycaemic control to IGlar, with a lower risk of nocturnal hypoglycaemia.

This article describes the academic works of the N.P. Kravkov (1865–1924), a prominent Russian pharmacologist, on the study of the endocrine glands.

In N.P. Kravkov’s laboratory, via experiments on rabbits and dogs, a method of isolating the pancreas and extracting its perfusate was developed based on passing Ringer-Locke’s solution through the vessels of the isolated gland. It was discovered that the perfusate contains a substance that reduces the level of glucose in the blood of healthy animals and, in large doses, causes hypoglycaemic coma. N.P. Kravkov called this substance pancreotoxin.

The experiments of N.P. Kravkov’s followers on the isolated hearts of animals showed that, for a heart in the normal condition, pancreotoxin decelerates the heartbeat and reduces the amplitude of contractions, whereas for the heart tired above a certain threshold, the opposite effect is observed.

The study of the blood vessels in isolated ears of rabbits and the eyes of frogs revealed antagonism between pancreotoxin and adrenalin: pancreotoxin weakens the vasoconstrictive effect of adrenalin and reduces its influence on the size of the pupil in frogs. It was also shown that passing the perfusate containing pancreotoxin through the adrenal gland increases the secretion of adrenalin.

Later, pancreotoxin was obtained in the dried form and used to prepare a drug prescribed to patients with diabetes in hospitals.

From its properties, pancreotoxin turned out to be insulin. It should be noted that the news that insulin had been isolated from the pancreas by the Canadian researchers F. Banting and C. Best reached Russia only after the researchers in N.P. Kravkov’s laboratory had extracted and studied pancreotoxin from isolated pancreases. Thus, N.P. Kravkov and foreign researchers discovered this hormone independently.

In experiments on the isolated adrenal glands of cattle, N.P. Kravkov and his collaborators obtained the perfusate containing an adrenalin-like substance produced in the medulla of the adrenal gland and a muscarine-like substance produced by the suprarenal cortex.

The research by N.P. Kravkov and his followers on the physiology, pathology and pharmacology of the glands of internal secretion at the beginning of the 20th century has proved to be of great importance for the development of endocrinology in Russia.