Diabetes mellitus

BACKGROUND: Type 2 diabetes (T2D) is multifactorial disease. NATION epidemiological study may provide the information about the prevalence of T2D and prediabetic state in patients with different risk factor combinations in Russian population.

AIMS: To evaluate the prevalence of T2D and prediabetic state in NATION cohort depending on the amount of diabetes risk factors.

MATERIALS AND METHODS: NATION is an epidemiological, cross-sectional study, designed to assess the prevalence of T2D in Russian adult population, where HbA_1c was used to establish T2D (HbAc≥6,5%) and prediabetes (5,7%≤HbA_1c<6,5%). Patients with T2D were either previously diagnosed or newly diagnosed. Current study presents an additional analysis of NATION cohort focused on the prevalence of T2D and prediabetic state among patients with different risk factor combinations.

RESULTS: T2D and prediabetic state prevalence gradually increased among patients with following risk factors (prevalence of T2D and prediabetes respectively): low physical activity (4,3%, 18,3%), rare fruit and vegetable consumption (4,8%, 18,7%), T2D family history (7,7%, 20,3%), age ≥45 years (9,5%, 31,3%), obesity grade 1 (9,6%, 30,3%), obesity grade 2 (14,6%, 37,8%), obesity grade 3 (20,1%, 39,7%), hypertension (14,7%, 38,2%), history of diabetes during pregnancy (14,1%, 24,7%). Prevalence of T2D with single and multiple risk factors was compared to the prevalence of T2D in young patients (<45 years) without additional diabetes risk factors. Age ≥45 years was associated with 7-fold increase in T2D prevalence; obesity – 8,8-fold; family history – 5,7-fold; hypertension – 10,8-fold (p<0,001 for comparisons of every group with patients <45 years of age without other risk factors). When one patient had several risk factors combined, the prevalence of T2D increased progressively: combination of age ≥45 years and family history led to 10,7-fold rise; combination of age ≥45 years and BMI≥30kg/m² – 11,2-fold; combination of age ≥45 years, family history and BMI≥30kg/m² – 15,3-fold; combination of age ≥45 years, family history, BMI≥30kg/m² and hypertension – 19,1-fold (p<0,001 for comparisons of every group with patients <45 years of age without other risk factors).

CONCLUSIONS: Presence of multiple risk factors, such as age ≥45 years, obesity and hypertension led to progressive increase in the prevalence of T2D and prediabetic state. These data are important to identify patients at the highest risk of T2D among Russian population.

BACKGROUND: Diabetes mellitus leads to disruption of the skin repair processes, but the leading mechanisms of this pathology have not yet been identified. In this regard, in our work, we decided to check how hyperglycaemia affects the process of keratinocyte phenotype changes during wound healing.

AIMS: To study the effect of hyperglycaemia on wound healing and differentiation of keratinocytes in a rat streptozotocin-induced diabetes model.

MATERIALS AND METHODS: Diabetes mellitus was induced in rats by using streptozotocin, 65 mg / kg, intraperitoneally, once. The wound was applied in the supra-scapular region on the 42nd day, after which (after 8, 16, and 24 days) the repair process was evaluated using histological methods. Immunohistochemistry was used to evaluate the expression of cytokeratin-10 and cytokeratin-17.

RESULTS: In rats with diabetes mellitus, wound healing slowed down in the later stages, compared with the control group. In general, wound healing was accompanied by an increase in the expression of cytokeratin-10 in its region compared with intact skin, and contractile keratinocytes activation was disrupted in diabetic rat wounds.

CONCLUSIONS: Hyperglycaemia slightly slows wound healing in rats and impairs contractile keratinocytes activation.

BACKGROUND: According to different studies, diabetes mellitus type 2 (DM2) is associated with higher mortality after undergoing coronary artery bypass grafting (CABG). Perioperative hyperglycaemia, even in non-DM2 patients, is associated with adverse outcomes after CABG. Thus, successful perioperative blood glucose control (BGC) is mandatory to reduce the risk of death and postoperative complications. Nowadays, the most effective method for BGC in the operating room is still unknown.

AIMS: To assess the continuous glucose monitoring (CGM) efficacy in association with insulin pump therapy in patients with coronary artery disease (CAD) and DM2 undergoing CABG in intra- and early postoperative periods.

METHODS: The study involved 97 patients undergoing isolated CABG. Patients were divided into two groups: 48 patients with DM2 and 49 patients without DM2. In both groups of patients, we used CGM in intra- and early postoperative periods (72 hours). In some patients with DM2, CGM was associated with insulin pump therapy (MiniMed Paradigm Veo 554/754) to successfully control postoperative glucose level. Besides commonly used tests (such as HbA_1C and lipid profile), we analysed high sensitive C-reactive protein (hs-CRP) levels before surgery, and then at 1 hour, 12 hours and 7 days after CABG in order to estimate their prognostic value.

RESULTS: During the 48 hours after CABG, there was a trend towards having higher glucose levels in both groups of patients with and without DM2 according to CGM. In patients with DM2, the glucose level was significantly increased (р<0,05). Insulin pump therapy resulted in glycemic control improvement in early follow-up (72 hours). Moreover, there were no hypoglycaemic episodes in patients on insulin pump therapy and also in patients prescribed bolus insulin therapy. We revealed the trend towards lower rate of postpericardiotomy syndrome (PCTS) in patients on insulin pump therapy compared to patients prescribed bolus insulin therapy in the early postoperative period (p=0,1). Hs-CRP level was lower in patients with DM2 who were on insulin pump therapy compared to patients prescribed bolus insulin therapy in the early postoperative period (р<0,05). This most likely confirms that insulin pump therapy decreases systemic inflammatory response.

CONCLUSIONS: Thus, we demonstrated the CGM feasibility, safety and efficacy in association with insulin pump therapy in patients with DM2 undergoing CABG.

Patients with diabetes mellitus (DM), which is a key factor in the development of kidney diseases, are increasingly competing for limited healthcare resources. Diabetic kidney disease (DKD) remains a significant cause of end-stage renal failure in the patients of many countries and is also associated with a high risk of cardiovascular pathology and mortality. The variety of clinical phenotypes of DKD in patients with type 2 diabetes mellitus (DM2) occurring due to a variety of pathogenetic factors and the characteristics of the evolution of complications under the influence of contemporary therapeutic methods, has been a special subject of discussion in recent years. Optimal control of the level of glycaemia and hypertension and timely blockade of the renin–angiotensin–aldosterone system do not provide sufficient protection for the kidneys. Over the recent decade, the nephroprotective potential of a group of modern anti-hyperglycaemic agents, i.e., glucagon-like peptide 1 receptor agonists (GLP1 RA) has been actively discussed. GLP1 RA have proven to be quite effective in controlling glycaemia and metabolic syndrome components (weight, systolic blood pressure and lipid profile) and in significantly reducing the risk of the primary, three-component endpoint (major adverse cardiac events: cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) according to large studies on cardiovascular safety. The renal effects of GLP1 RA are attributed to a wide range of direct and indirect effects of glucagon-like peptide-1 on renal structures and functions owing to their anti-inflammatory, anti-oxidant and anti-apoptotic properties.

Research results show that poor glycemic control and recurrent episodes of severe hypoglycaemia are associated with a decrease in cognitive function in elderly people with type 2 diabetes mellitus (T2DM). On the other hand, patients with diabetes mellitus associated with cognitive impairment/dementia are most at risk of developing hypoglycaemic conditions. It is obvious that the relationship between hypoglycaemia and dementia is very complex and has a mutually aggravating nature.

Studies also show that individuals of older age groups with diabetes and cognitive impairment have a high risk of developing hypoglycaemic conditions, such as unwanted side effects from glucose-lowering therapy. In this case, of particular interest is the question that is being actively studied at the present time, which is concerning the effect of different groups of glucose-lowering antidiabetic drugs on the cognitive status and the rate of cognitive decline in diabetic patients with cognitive impairment.

In this review, we attempted to summarise, systematise, and present data available in the literature concerning the effect of hypoglycaemia on the risk of cognitive impairment and dementia in elderly and senile patients with type-2 diabetes, as well as the degree of participation in this process of of various groups of sugar-lowering antidiabetic drugs.

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus (DM). As DR progresses, it could be complicated with a significant decrease or complete loss of vision. It is the leading cause of blindness in the working-age population and, according to global estimates, occurs in one in every three patients with diabetes. DR has been studied for more than 160 years, and the implementation of retinal laser coagulation into clinical practice in the 20th century, and then vascular endothelial growth factor (VEGF) inhibitors in the 21th century, allowed us to influence vascular proliferation in DR and reduce the risk of vision loss from diabetic macular oedema (DME). However, these tools can only stop the progression of DR at the stages with risk of complications with vision loss, and prevention – screenings and the impact on risk factors (hyperglycaemia, arterial hypertension, and dyslipidemia) – remains as the main method of management of DR. Possible new risk factors (hypodynamy, obesity, body weight deficiency, and obstructive sleep apnoea syndrome) attract a lot of attention, and there is ongoing research for early markers of DR in the fundus, which could allow more active influence on the pathological process in its early stages. This review focuses on epidemiology, history of research, proven and possible risk factors, and current and promising approaches to the prevention and treatment of DR, including accurate, less traumatic laser techniques (PASCAL, NAVILAS, and D-MPL), and intravitreal antiangiogenic drugs in studies.

According to key diabetic studies, the early use of metformin glucose lowering therapy is associated with a reduced risk of developing micro- and, in the long term, 10-year follow-up, macrovascular complications and cardiovascular mortality. Short-term studies results on combined glucose lowering therapy with metformin suggests that combination therapy can have several advantages on the one side from the effectiveness of glycemic control and on another side from positive effect on the development of complications of type 2 diabetes. The question of the start time of combined hypoglycemic therapy remains open. According to the results of recent large-scale studies, real world evidence data, careful glycemic control during the first year from the moment of diagnosis of type 2 diabetes is crucial for further management of the disease and slow the progression of complications.

However, due to the fact that the clinical benefits of early combination therapy were not demonstrated in randomized clinical trials, this approach, despite the theoretical background, was not recommended for widespread use in international guidelines for the treatment diabetes patients. Russian algorithms on the treatment diabetes patients recommend combined glucose lowering therapy at the start of treatment at a HbA1c level of 1% higher than the target.

A 5-year VERIFY study results were demonstrated long-term sustained glycemic control in combination with vildagliptin + metformin prescribed for native diabetes patients with relatively low HbA1c values, as well as the advantages of this approach in comparison with the standard strategy for phased intensification of monotherapy. The results of the VERIFY study provided a wealth of information to discuss early treatment intensification, the clinical benefits of this approach and a possible review of the treatment strategy for native diabetes patients.