Vol 29, No 4 (2022)

Diabetes mellitus type 3c (DM3c) develops as a result of a number of exocrine diseases of the pancreas: chronic pancreatitis, pancreatic ductal adenocarcinoma of the, hemochromatosis, cystic fibrosis, and previous pancreatic surgery. Inflammation and fibrosis in the pancreatic tissue cause damage to both endocrine and exocrine functions, resulting in decreased levels of insulin, glucagon, and exocrine function. The prevalence of DM3c reaches 5-10% among diabetic patients in developed countries. In 1.8% of adults with newly diagnosed diabetes, diabetes can be classified as type 3 diabetes, and individuals with this disease have varying degrees of exocrine and endocrine dysfunction. DM3c, or impaired glucose tolerance, develops in 25-75% of adults with chronic pancreatitis. After acute pancreatitis DM3c develops in a year in 15% of patients, and an even in greater proportion of patients - in 5 years. Pancreatitis increases the risk of pancreatic cancer in diabetic patients, and the highest risk of this cancer occurs in DM3c patients. The incidence of newly diagnosed DM varied depending on the type of surgical intervention: from 9 to 24% after pancreatoduodenal resection (PDR), 3-40% after distal and 0-14% after central pancreatectomy. The type of resection, high preoperative HbAlc and fasting glucose levels, and low pancreatic residual volume after surgery had the strongest associations with new onset DM. Three mandatory criteria for diagnosing DM3c have been identified: the presence of exocrine pancreatic insufficiency, pathological changes during its visualization (endoscopic ultrasound and other instrumental methods), and the absence of autoantibodies to DM1. Minor criteria include impaired β-cell function, low levels of fat-soluble vitamins (A, D, E, and K), lack of insulin resistance, and impaired secretion of incretins and pancreatic polypeptide. It is assumed that the gut microbiome of DM3c patients differs from that of patients with type 1 and type 2 diabetes mellitus. Early recognition of DM3c associated with pancreatic ductal adenocarcinoma improves patient survival. In the presence of unexpressed hyperglycemia and insulin resistance, the appointment of metformin should be considered, since side effects in the form of weight loss and disorders of the gastrointestinal tract are undesirable in DM3c. The main defect in DM3c is insulin deficiency; insulin which is prescribed when oral hypoglycemic therapy has failed, but it may increase the risk of malignancy in addition to weight gain and hypoglycemia. In progressive DM3c, a basal-bolus insulin regimen should be used, with attention paid to education, continuous glycemic monitoring, and the possible use of insulin pumps. Derivatives of oxyntomodulin, an incretin mimetic with an optimal ratio of the effects of activation of glucagon-like peptide-1 and the glucagon receptor, may be promising for the treatment of DM3c. With exocrine insufficiency, replacement therapy with pancreatic enzymes is recommended; treatment with a pancreatic polypeptide appears promising. Islet transplantation has become an established approach to β-cell replacement therapy for the treatment of insulin-deficient diabetes. As an alternative approach, human pluripotent stem cells can provide an unlimited number of cells with the ability to secrete insulin in response to high blood glucose levels. Beta cells, progenitors of pluripotent stem cells, are the best candidate given the availability of encapsulation technology.

Background. The progressive course of type 2 diabetes mellitus (DM2) often necessitates combination therapy with oral antihypergly-cemic agents, and eventually insulin, alone or in combination with other antidiabetic agents, may become necessary to maintain glucose levels. Objective. Reporting of results of the VERTIS CV sub-study. Methods. VERTIS CV is a randomized, double-blind, parallel group, placebo-controlled study of ertugliflozin cardiovascular outcomes. Patients were randomly assigned to placebo and ertugliflozin at a dose of 5 or 15 mg/day. A sub-study included patients receiving a stable dose of insulin >20 IU/day. Of8246patients randomized to VERTIS CV, 1065 were included in the sub-study (68.2% male patients, mean age 64.8±7.8 years; DM2 duration: 16.7±9.0 years; glycosylated hemoglobin (HbA1c): 8.4±1.0%). The main end point was the change in HbA1c level from baseline at 18 weeks. Secondary endpoints were changes in fasting plasma glucose (FPG) level, body weight (BW), proportion of patients with HbA1c <7%, systolic blood pressure (SBP), diastolic blood pressure (DBP), and insulin dose. Results. At 18 week, the mean change from baseline in HbA1c level with ertugliflozin 5 and 15 mg versus placebo (95% CI) was -0.58% (-0.71-0.44) and -0.65% (-0.78--0.51), respectively (P<0.001 for both). Ertugliflozin significantly reduced FPG, BW, and SBP. In women, the incidence of genital fungal infections was higher with ertugliflozin (3.5%) compared with placebo (0.0%). The frequency of symptomatic hypoglycemia was similar in the treatment groups. Conclusion. The addition of ertugliflozin to insulin improved glycemic control, BW, and SBP at 18 weeks in DM2 patients with atherosclerotic cardiovascular disease compared with placebo.

Background. Thyroid function disorders are often detected in comorbid patients, including in patients with chronic kidney disease (CKD). A decrease in the functional activity of the thyroid gland is associated with dysproteinemia, atherogenic dyslipidemia, electrolyte and nitrogen metabolism disorders. Recommendations for the detection and treatment of thyroid dysfunction in CKD patients have not yet been developed. Objective. Evaluation of the effect of levothyroxine replacement therapy on blood lipid profile and estimated glomerular filtration rate (eGFR) in patients with subclinical hypothyroidism and various CKD stages. Methods. 457 patients with various CKD stages were examined. Subclinical hypothyroidism (SHT) was revealed in 73 (16%) patients. SHT was associated with severe disorders of protein metabolism due to a decrease in the total protein (P=0.031) and albumin (P=0.047) levels, a significant increase in daily proteinuria (P=0.002), a decrease in the total calcium level (P=0.002), an increase in phosphorus inorganic (P=0.011) and chloride (P=0.017) levels, atherogenic dyslipidemia (increased total cholesterol (p<0.001), low-density lipoproteins; (P=0.045) and very low-density lipoproteins (P=0.025) levels). Patients were then randomized to treatment with levothyroxine (n=36) and observation (n=36). Statistical analysis was carried out using the StatTech v. 2.6.1. Results. After re-examination of patients in the treatment group at 6 months, there was a significant decrease in the thyroid-stimulating hormone (P<0.001), total cholesterol (P<0.001), low-density lipoproteins (P<0.001), creatinine (P=0.002), urea (P= 0.001) levels, and increased fT3 (P=0.028), fT4 (P=0.002), eGFR (P=0.003), and albumin (P=0.019) levels. In the observation group, a significant decrease in the high-density lipoprotein (P=0.010), thyroid-stimulating hormone (P=0.001) and total protein (P=0.045) levels over time was noted. Conclusion. SHT in CKD patients was associated with disorders of protein and lipid metabolism, abnormalities in the electrolyte levels. Replacement therapy with levothyroxine in CKD patients with SHT led to a significant improvement in blood lipids, eGFR, a decrease in creatinine and urea, and an increase in albumin levels.

Background. Psoriasis against the background of carbohydrate metabolism disorders has a severe course and significantly worsens the quality of life and prognosis of patients. For this reason, the task of modern health care is to develop new affordable diabetes screening tools for early diagnosis and selection of rational therapy. Objective. Evaluation of the predictive value (effectiveness) of the diabetes screening questionnaire for predicting diabetes mellitus in patients with psoriasis in comparison with traditional scoring methods for diagnosing diseases. Methods. The study involved 410 patients with various forms of psoriasis, who were admitted in the Dermatology Department of the Novosibirsk Regional Clinical Dermatovenerologic Dispensary. As a quantitative measure of the effect when comparing relative indicators, we used the odds ratio, defined as the ratio of the probability of an event occurring in a group exposed to a risk factor to the probability of an event occurring in the control group. Multiple logistic regression (MLR) was used to obtain a predictive model for the presence/absence of diabetes in patients with psoriasis. Results. The accuracy of the obtained model DEWS1&2 + Diabetes Prediction Score Table in patients with psoriasis was 85.6%. Conclusion. The recognition of psoriasis as a systemic disease characterized by chronic inflammation, a widespread dysimmune background, and a dysmetabolic environment allows to expand the preventive and therapeutic approach to psoriasis.

This article discusses the clinical case of managing a patient with type 1 diabetes mellitus, initially treated with multiple injections of first-generation insulin analogues. On this therapy, disease control was unsatisfactory. There were episodes of postprandial hypoglycemia 3 hours after eating. HbAlc level - 8.2%; the patient was 54% of the time in the target glycemic range, 3% of the time - in the hypoglycemic range, and 43% of the time - in the hyperglycemic range. After switching to the last generation insulin analogue (superfast-acting insulin aspart), it was possible to avoid episodes of postprandial hypoglycemia. Subsequently, episodes of nocturnal hypoglycemia occurred, which were managed by switching the patient from two injections of a first-generation basal insulin analogue to one injection of a last-gen-eration basal insulin analogue (degludec). The combined use of the last generation analogues made it possible to achieve normoglycemia without episodes of hypoglycemia (HbAlc - 6.3%, time spent in the target range - 71%, time spent in the hypoglycemic range - 0%).