Vol 17, No 1 (2014)

Cover Page
Epidemiology
Current report from Russian Diabetic Retinopathy Register
Lipatov D.V., Aleksandrova V.K., Atarshchikov D.S., Bessmertnaya E.G., Kon I.L., Kuz'min A.G., Smirnova N.B., Tolkacheva A.A., Chistyakov T.A.

Abstract

A pandemic expansion of diabetes mellitus (DM) observed nowadays across the globe is increasingly acknowledged as a disaster by all peoples of the world. Statistical analysis indicates an annual increase in prevalence of DM in Russian Federation that had reached 3 779 423 registered patients by 01.01.2013. Besides the humanitarian aspects, DM poses severe economic challenges for this country ? challenges that stem both from high mortality and growing disability rate due to limb loss, decrease in visual acuity and need for hemodialysis, plaguing many DM patients.
Aim.
To produce an epidemiological evaluation based on the dynamics of prevalence of diabetic retinopathy in the Russian Federation ? nationwide and in individual regions ? across the last 13 years.
Materials and Methods.
Current survey included patients from various regions of the Russian Federation that were examined during epidemiological missions conducted by the federal Endocrinology Research Centre (2000?2009), as well as National Programmes ?Health? (2007) and ?Diabetes ? Learn In Advance? (2012?2013).
Results.
In the Russian Federation registered more than 630,000 patients with different stages of diabetic retinopathy. The prevalence of diabetic retinopathy among adults (18 years and older) with type 1 diabetes is 35.25%, while in type 2 diabetes - 16.67%. On average, this means that almost one in five patients (17.63%) with diabetes have certain eye problems.
Conclusion.
In summary, our data indicate a dramatic growth in the rate of diabetic ocular complications, with a particular increase in proliferative diabetic retinopathy, complicated cataract and neovascular glaucoma. These findings call for an even closer attention to early diagnostics, adequate management and, above everything else, timely prevention of ocular pathologies in patients with DM.
Diabetes mellitus. 2014;17(1):4-7
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Optimizing screening procedures for early detection of glycemic disorders
Misnikova I.V., Dreval A.V., Kovaleva Y.A., Gubkina V.A., Lakeeva T.S.

Abstract

Aim.
To estimate the actual prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in individuals at high risk for T2DM and to develop an optimized stepwise screening procedure.
Materials and Methods.
A mobile diagnostic unit conducted outpatient screening for glycemic disorders. First stage of the survey included distribution of the FINDRISK questionnaire within the target subpopulation. At the second stage, study groups were formed based on the acquired data. Third stage involved clinical evaluation of glucose homeostasis by testing HbA1c levels and performing oral glucose tolerance test (OGTT). Individuals considered at high risk for development of T2DM were referred to specialized educational programs. A total of 2200 subjects were included in the present survey. In 1377 cases OGTT was supplemented with the testing of HbA1c. Statistical processing of the data was performed with Microsoft Excel software utility.
Results.
The interpretation of OGTT results identified 53.5% (n=1176) of study subjects as positive for glycemic disorders: 26.7% (n=587) with T2DM and 26.8% (n=589) with prediabetes, respectively. Impaired glucose tolerance was detected in 12.1% (n=266), impaired fasting glucose ? in 9.1% (n=199), and the combination of these two conditions ? in 5.6% (n=124) of examined individuals, respectively. In 235 subjects (17.1%) T2DM was diagnosed by means of HbA1c testing. 45% of examined individuals (n=620) had HbA1c<5.7%, 37.9% (n=522) showed HbA1c between 5.7% and 6.4%.
Conclusion.
A stepwise procedure allows for higher screening performance in subjects at risk for development of T2DM. Overall prevalence of T2DM, identified either by OGTT or HbA1c testing made up 31,1% of the examined sampling. Results from both methods were in agreement in 39.2% of cases.
Diabetes mellitus. 2014;17(1):8-14
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Pathogenesis
A mathematical model for stratification of LADA risk groups
Tikhonova T.M.

Abstract

Aim.
To stratify risk groups via discriminant analysis based on the most clinically relevant indications of LADA onset derived from medical history.
Materials and Methods.
Present study included 141 patients with diabetes mellitus (DM) of whom 65 had preliminary diagnosis of LADA, 40 patients were diagnosed with type 1 diabetes mellitus (T1DM) and 36 ? with type 2 diabetes mellitus (T2DM). Discriminant analysis was performed to evaluate the differences between the clinical onsets in study groups.
Results.
Aside from torpid onset with early evidence for insulin resistance, clinical characteristics of LADA included diagnosis during random examination, progressive loss of body mass, hyperglycemia greater than 14 mmol/L at the diagnosis and, possibly, ketonuria without history of acute ketoacidosis.
Conclusion.
Discriminant analysis is beneficial in stratifying risk groups for the development of LADA.

Diabetes mellitus. 2014;17(1):15-20
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Hormonal, metabolic and genetic predictors of metformin efficacy in patients with diabetes mellitus and cancer
Bershteyn L.M., Vasil'ev D.A., Ievleva A.G., Poroshina T.E., Imyanitov E.N.

Abstract

Aims.
  1. To compare hormonal and metabolic profile of type 2 diabetes mellitus patients (T2DM) with or without neoplastic processes with the data from screening for SNPs affecting sensitivity to metformin.
  2. To compare the abovementioned parameters including relevant genotype frequency in patients with positive and negative response to metformin.
Materials and Methods.
A total of 167 patients, all female, aged 43 to 88 years in menopause no shorter than 1 year, with or without history of T2DM were enrolled in this study. 156 patients underwent genetic screening for SNPs that were previously suggested as relevant to metformin efficacy. 55 patients received metformin 1000-1700 g daily with hormonal and metabolic monitoring and assessment of surrogate antineoplastic markers (such as endometrial thickness and mammographic density of mammary glands).
Results.
There was no unifying hormonal or metabolic phenotype for patients with given metformin-associated SNPs. However, we observed a certain trend for alterations in HOMA-IR and plasma estradiol levels. Dyslipidemia and elevated estradiol levels were positively associated with both types of positive response to metformin ? ?metabolic? and ?antineoplastic? ? though the latter was observed less frequently. Our data suggests that among 8 studied SNPs, the OCT1_R61C genotype (organic cation transporter-1) carriers require more close attention.
Conclusion.
Larger studies are required for further elucidation of the genetic background for metformin action in patients with various forms of cancer.
Diabetes mellitus. 2014;17(1):21-28
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Markers for hepatic autoimmune disorders in patients with type 1 diabetes mellitus
Derevyanko O.S., Dalantaeva N.S., Ivanova O.N., Goncharov N.P., Nikonova T.V., Smirnova O.M.

Abstract

Aim.
To assess the occurrence of autoantibodies characteristic of autoimmune hepatitis in patients with type 1 diabetes mellitus (T1DM), and to analyze clinical features of positive subjects.
Materials and Methods.
. 84 patients (39 male, 45 female) with T1DM were subdivided into two groups and underwent biochemical, immunologic and instrumental examination.
Results.
Markers for hepatic autoimmune disorders were found to be highly prevalent in patients with T1DM, even in those asymptomatic according to clinical and instrumental diagnostic methods.
Conclusion.
 Our data suggests that T1DM patients are at higher risk of corresponding, though possibly asymptomatic autoimmune disorders.
Diabetes mellitus. 2014;17(1):29-33
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Cardiology
Effects of diabetes compensation by various classes of antihyperglycemic agents on endovascular intervention outcomes in patients with type 2 diabetes mellitus
Michurova M.S., Kononenko I.V., Smirnova O.M., Kalashnikov V.Y.

Abstract

Introduction of drug-eluting stents for percutaneous coronary interventions opened novel options for treating coronary heart disease (CHD) in patients with diabetes mellitus. However, mortality and myocardial infarction rates are still higher among diabetes patients. They also require repeated revascularization of the target vessel more often than euglycemic individuals do. Current review discusses possible effects of diabetes compensation by various classes of antihyperglycemic agents on endovascular intervention outcomes.
Diabetes mellitus. 2014;17(1):34-40
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Assessment of carotid intima-media thickness in patients with type 2 diabetes mellitus and arterial hypertension
Bondar' I.A., Demin A.A., Shabel'nikova O.Y., Onyanova V.A.

Abstract

Aim.
 Atherosclerosis is one of the most important complications of type 2 diabetes mellitus (T2DM). In the present study, we aimed to assess the carotid intima-media thickness in type 2 diabetes patients with the arterial hypertension (AH) comorbidity.
Materials and Methods.
 96 patients with T2DM and AH (30M/66F, aged 53.4?5.4 years, duration of diabetes 7.7?7.5 years) and 30 hypertensive patients without diabetes (12M/18F, aged 53.1?6.0 years) were enrolled in this study. Stiffness indices for right and left common carotid arteries were assessed with noninvasive ultrasound method in both groups.
Results.
Difference in the intima-media thickness was statistically significant between diabetic and euglycemic patients (1.26?0.17 mm vs. 1.10?0.14 mm, respectively; p<0.01). Data from patients with diabetes duration less than 1 year was not significantly different from euglycemic controls (1.20?0.20 mm vs. 1.10?0.14 mm, respectively; p>0.05), in contrast with their counterparts with longer experience of T2DM (1.27?0.17 mm vs. 1.10?0.14 mm; p<0.05). In patients with AH and T2DM, intima-media thickness positively correlated with systolic blood pressure (r=0.521, p<0.01), duration of diabetes (r=0.203, p<0.05), fasting plasma glucose (r=0.215, p<0.05) and plasma HDL (r=-0.288, p<0.05). In euglycemic patients with AH we observed a correlation between the intima-media thickness and systolic blood pressure (r=0.284, p<0.05).
Conclusion.
Our data indicate that patients with AH and T2DM exhibit more profound alterations in the intima-media compared to their hypertensive but euglycemic counterparts. The increase in intima-media thickness in DM patients depends not only on the level of systolic blood pressure, but also on the duration of diabetes, on fasting plasma glucose and on plasma levels of HDL.
Diabetes mellitus. 2014;17(1):41-46
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Chronic Kidney Disease
Insulin resistance as a systemic player in renal pathology: a review
Tyuzikov I.A.

Abstract

Current review provides a multifaceted analysis of epidemiological, clinical and experimental evidence for insulin resistance as a systemic player in the development of renal pathology. We discuss both established and potential mechanisms for this effect. Aside from being a marker for glycemic disorders, insulin resistance was shown to be an independent predictor of renal pathology, including such chronic conditions as urolithiasis, renal cysts and malignant renal neoplasms. Early detection and correction of insulin resistance is a promising approach to diagnostics, treatment and prevention of renal pathology.
Diabetes mellitus. 2014;17(1):47-56
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Diabetic foot
Effects of growth factors and cytokins on soft tissue regeneration in patients with diabetes mellitus
Zaytseva E.L., Tokmakova A.Y.

Abstract

Delayed wound healing is characteristic of a glycemic disorder and often results in trophic ulcer formation, ? a process still poorly understood but likely multifaceted. Current review addresses latest reports from cellular and molecular studies of soft tissue regeneration in patients with diabetes mellitus.
Diabetes mellitus. 2014;17(1):57-62
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Genetic and cellular techniques emerge as promising modalities for the treatment of diabetic foot syndrome
Konenkov V.I., Klimontov V.V.

Abstract

Two patient groups potentially to benefit most from these novel methods are patients with critical lower limb ischemia (CLLI) in whom angiosurgery is not indicated, and patients with trophic ulcers resistant to conventional therapy. A series of clinical trials has shown positive effects of transferring VEGF, HIF-1, FGF, PDGF, HGF and certain other growth factor genes to stimulate blood vessel formation and healing of diabetic ulcers. Autologous transplantation of mononuclear bone marrow and peripheral blood cells, endothelial progenitor cells, mesenchymal stem cells and stromal cell of the adipose tissue has also demonstrated its clinical potential in patients with diabetes mellitus and CLLI. Randomized clinical trials report beneficial effects of gene and cell therapy on such surrogate endpoints as ischemic index, rest pain and ulcer healing, though data on amputation rates is controversial. Further studies are necessary to determine optimal dosage and route of administration of biological agents and predictors of their efficacy, as well as long-term safety of these novel treatment modalities.
Diabetes mellitus. 2014;17(1):63-69
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Diagnosis, control, treatment
Comparative evaluation of several parameters of glycemic homeostasis in patients with functional pituitary adenomas
Mikityuk .R., Khizhnyak O.O., Sulima T.N.

Abstract

Aim.
To investigate glycemic homeostasis in patients with acromegaly and hyperprolactinaemia due to functional pituitary adenoma.
Materials and Methods.
We enrolled 48 patients with somatotropinoma (Group 1), 19 patients with somatomammotropinoma (Group 2) and 24 patients with prolactinoma (Group 3) with no history of glycemic disorders. Median age was 48.63?9.98 years; median disease duration was 13.1?6.9 years. The comparison group was composed of overweight or obese patients (n=75). We conducted a comparative analysis of glycemic parameters (Glc0, immunoreactive insulin, HOMA2_S%, HOMA2_B% и HOMA2_IR, Ssum and S under isolated segments of the glycemic curve). We also tested their correlation with plasma levels of growth hormone, prolactin and IGF-1.
Results.
We detected hyperinsulinemia (>20 ?U/mL) in 35.1% of participants from Group 1, 33.3% and 25% from groups 2 and 3, respectively. There was no statistically significant difference between glycemic parameters of the study groups, though patients were mildly insulin resistant (HOMA2_IR 1.88 to 2.38 units) independantly from tumour secretory activity. Groups 1 and 2 were characterized by significantly higher fasting blood glucose levels vs. comparison group (though still within the reference values), and glucose homeostasis was maintained with lower activity of pancreatic ?-cells. Average Ssumanalysis showed lower glucose tolerance in groups 1 and 2 vs. Group 3. Median S values under isolated glycemic curve segments were significantly higher than in comparison group. Plasma levels of growth hormone did not correlate with Ssum and S parameters in groups 1 and 2. There was a linear correlation between Ssum and plasma IGF-1 levels in patients from Group 1 (r=0.45; p=0.006). We also noted that Ssum had a non-linear correlation with plasma prolactin levels in patients from Group 3 (r=0.41; p<0.05).
Conclusion.
Postprandial area under the glycemic curve has positive linear association with plasma IGF-1 (but not growth hormone) in patients with somatotropinoma.
Diabetes mellitus. 2014;17(1):70-74
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Hypoglycemia in type 2 diabetes patients treated with insulin: the advantages of continuous glucose monitoring
Klimontov V.V., Tsiberkin A.I., Fazullina O.N., Prudnikova M.A., Tyan N.V., Konenkov V.I.

Abstract

Aims.
 To determine the incidence and risk factors for hypoglycemia in elderly insulin-treated type 2 diabetes mellitus (T2DM) patients by means of continuous glucose monitoring (CGM).
Materials and Methods.
 We observed seventy-six hospitalized patients with T2DM, aged 65 to 79 years. Treatment with basal insulin (n=36), premixed insulin (n=12) or basal-bolus insulin regimen (n=28) was followed by metformin (n=44), glimepiride (n=14) and dipeptidyl peptidase-4 inhibitors (n=14). 2-days CGM with retrospective data analysis was performed in all patients. During CGM, three fasting and three 2-h postprandial finger-prick glucose values were obtained daily with portable glucose meter.
Results.
 Hypoglycemia (identified as blood glucose <3.9 mmol/l) was registered in 17 (22%) patients by glucose meter and in 55 (72%) patients by CGM. Most of the CGM-registered hypoglycemic events (72%) were not recognized by patients. Nocturnal hypoglycemic events were revealed in 48 subjects (63%). Patients with hypoglycemia had lower interstitial glucose (median, 25?75 percentile: 7.0, 6.4?8.3 vs. 8.3, 7.4?8.5 mmol/l, p=0.01) and higher glucose variability (2.5, 1.9?3.1 vs. 1.8, 1.4?2.2 mmol/l, respectively; p=0.0008). There was no significant difference between the groups regarding daily insulin dose, HbA1c or T2DM duration. In a model of stepwise discriminant analysis, age, duration of insulin therapy, mean interstitial glucose levels and glycemic variability showed associations with hypoglycemia (accuracy rate 97.5%, p=0.005).
Conclusion.
The unrecognized hypoglycemia is a common complication in elderly T2DM patients on insulin therapy. Compared to conventional blood glucose monitoring, two-day CGM is superior in detection of asymptomatic hypoglycemia in this patient group. Age, duration of insulin therapy, mean glucose levels and glucose variability were associated with hypoglycemic events in elderly patients with T2DM.
Diabetes mellitus. 2014;17(1):75-80
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Lecture
Clinical implementetion of vildagliptin: data from recent studies comparing incretin-based medications
Biryukova E.V.

Abstract

The introduction of DPP-4 inhibitors substantially increased therapeutic options for type 2 diabetes mellitus (T2DM). The unique mechanism of action allows using these agents both as monotherapy and in combination with conventional anti-diabetes drugs. Evidence base for efficacy and safety of DPP-4 inhibitors deepens every year, but to date only a few studies addressed direct comparison between individual agents within this pharmacological class.
Current article presents data from the studies comparing vildagliptin with other DPP-4 inhibitors, as well as GLP-1 agonists.
Diabetes mellitus. 2014;17(1):81-84
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Letters
Comments to: ?Type 2 diabetes mellitus ? time to change the concept?
Udovichenko O.V.

Abstract

Authors of the paper ?Diabetes mellitus ? time to change the concept? (Diabetes Mellitus, 2013; №1: 91) address weight-reduction treatment modalities (including bariatric surgery) as the pivotal approach to type 2 diabetes management. While acknowledging the importance of weight loss in patients with type 2 diabetes mellitus (T2DM), this short letter aims to advise the endocrinology community against viewing bariatric surgery as the ultimate solution of all challenges of T2DM.
Diabetes mellitus. 2014;17(1):85-86
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Response to Comment on ?Type 2 diabetes mellitus ? time to change the concept?
Levit S., Filippov Y.I., Gorelyshev A.S.

Abstract

In this short letter, we comment on the major points of the response to our previous paper. In particular, we provide further clarification of our position on the issue of bariatric surgery, on principal pharmacological approaches to the management of type 2 diabetes mellitus and on the cause-effect interplay between obesity and development of type 2 diabetes.
Diabetes mellitus. 2014;17(1):87-88
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Memorable events
Vasily Baranov (1899?1988). On 115th anniversary of the prominent scientist?s birth
Patrakeeva E.M.

Abstract

Vasily Baranov was a distinguished scientist in the field of endocrinology, many of whose studies remain relevant today. He was blessed with a long and productive life filled with passion for work and insightful research. The task of an accurate depiction of his legacy within the boundaries of a single article is quite challenging, as his works encompassed a wide spectrum of scientific, medical and organizational problems.
Diabetes mellitus. 2014;17(1):89-92
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