Patient-perceived benefits and risks of off-label use of SGLT2 inhibitors and GLP-1 receptor agonists in type 1 diabetes: a structured qualitative assessment.

Background: Patients with type 1 diabetes mellitus (T1DM) may have suboptimal glucose control and are interested in the use of adjuvant therapies. Objectives: To determine, from the patients' perspective, the reasons for initiation of glucagon-like peptide 1 receptor agonist (GLP-1RA) and/or sodium glucose cotransporter 2 inhibitor (SGLT2i) in treating T1DM; perceived benefits/side effects, reasons for discontinuation, and willingness to reinitiate therapy. Design: Retrospective chart review with structured telephone interviews. Methods: We identified patients with T1DM treated with a GLP-1RA and/or SGLT2i for >3 months at University of Texas Southwestern Medical Center (Dallas, TX, USA) and Poznan University (Poznan, Poland). We conducted structured telephone interviews regarding their experiences. Results: We interviewed 68 participants treated with GLP-1RA and 82 with SGLT2i. Treatment was initiated for improving glycemic control (as reported by 61.8% versus 81.7% of GLP-1RA and SGLT2i users, respectively), weight loss/appetite suppression (51.4% versus 23.2%) and to reduce insulin requirement (13.2% versus 11%). Most participants (86.8% of GLP-1RA and 89.0% of SGLT2i users) reported ⩾1 benefit attributed to therapy. Reported benefits were improved glycemic control (reported by 58.8% versus 82.9% of GLP-1RA and SGLT2i users, respectively), weight loss/appetite suppression (63.2% versus 30.5%), and reduced insulin requirement (27.9% versus 34.1%). More GLP-1RA users reported side effects versus SGLT2i users (63.2% versus 36.6%); 22.6% discontinued GLP-1RA due to side effects versus 11.0% SGLT2i users. Diabetic ketoacidosis (DKA) was reported by 4.9% of SGLT2i users, but none in GLP-1RA users. Of those who discontinued medication, 60.7% of GLP-1RA versus 56.0% of SGLT2i prior users were willing to reinitiate treatment. Conclusions: Patients with T1DM report initiating adjuvant treatment with GLP-1RA and/or SGLT2i to improve glycemic control and lose weight; most patients reported perceived benefits from these therapies. Side effects (including DKA) are reported more commonly in real life than in clinical trials. Given patient interest in these medications, further studies should evaluate the long-term risk-benefits ratio in larger cohorts.

Better Gingival Status in Patients with Comorbidity of Type 1 Diabetes and Thyroiditis in Comparison with Patients with Type 1 Diabetes and No Thyroid Disease-A Preliminary Study.

Periodontal disease has been postulated as one of the chronic complications of diabetes. The prevalence of autoimmune thyroiditis in type 1 diabetes (T1D) is higher. The aim of the study was to determine the association between the presence of thyroiditis and gingival status in adults with T1D. A total of 264 patients, 119 men aged 18-45, diagnosed with T1D were included. For further analysis, the study group was divided into two subgroups, with or without autoimmune thyroiditis. Gingival status was assessed with the use of gingival indices. Patients diagnosed with T1D and thyroiditis presented lower plaque accumulation (p = 0.01) and lower-grade gingivitis (p = 0.02). Approximal Plaque Index (API) in all study groups correlated positively with age (Rs = 0.24; p = 0.0001), body mass index (BMI) (Rs = 0.22; p = 0.0008), hemoglobin A1c (HbA1c) (Rs = 0.18; p = 0.006), high-sensitivity C-Reactive Protein (hsCRP) (Rs = 0.17; p = 0.009), total cholesterol (T-Chol) (Rs = 0.17; p = 0.01) and negatively with thyroid-stimulating hormone (TSH) (Rs = -0.2; p = 0.02). Stepwise multivariate linear regression analysis indicated TSH, BMI and gender as independent predictors of dental plaque accumulation in patients with T1D. Autoimmune thyroiditis was associated with a lower accumulation of dental plaque and better gingival status in patients with T1D.

Influence of Chlorhexidine and Cetylpyridine on Periodontal Status and Indicators of Oxidative Stress in Patients with Type 1 Diabetes.

OBJECTIVE: One of the treatment goals in type 1 diabetes and periodontitis is to address chronic inflammation to prevent the development of neurovascular complications. The aim of this study was to assess the local anti-inflammatory effects of chlorhexidine digluconate and cetylpyridine chloride on periodontal status and indicators of oxidative stress in saliva in patients with type 1 diabetes. MATERIALS AND METHODS: A total of 42 subjects aged 27 (interquartile range, IQR 22-35) years, with type 1 diabetes for a duration of 12 (IQR 9-18) years, and glycated hemoglobin 8.05 (IQR 7.1-9.4)% were included. Patients were examined twice-initially, and after 14 days of using toothpaste with chlorhexidine and cetylpyridine. Clinical examination of gingival tissues was performed. Certain oxidative stress markers (TP, TEAC, TBARS, AOPP) were measured in the saliva samples. RESULTS: There were significant changes in clinical indicators of periodontal status before and after the application of the toothpaste (API before 0.35 (0.24-0.65) vs. API after 0.265 (0.18-0.39), p = 0.03; SBI before 0.07 (0.04-0.15) vs. SBI after 0.035 (0-0.06), p = 0.002; GI before 0.88 (0.46-1) vs. GI after 0.67 (0.25-1), p = 0.0008). The concentration of saliva TBARS decreased (p = 0.00005) and TEAC increased (p = 0.09). CONCLUSION: Proper oral hygiene supported by antibacterial chemicals may improve the periodontal status and reduce inflammation.

Atelocollagen Application in Human Periodontal Tissue Treatment-A Pilot Study.

BACKGROUND: The aim of this study is the clinical observation of gingival tissue condition after atelocollagen injection. METHODS: In 18 patients, 97 gingival class I Miller recessions were divided according to recession height, gingival papillae loss and thickness of gingivae. Atelocollagen (Linerase, 100 mg) was injected into keratinized gingivae twice or thrice, at two-week intervals. RESULTS: Statistically significant changes in gingival recession, amount of gingival papillae loss and thickness of gingiva were observed, after both two and three collagen injections. Although the degree (height) of recession decreased and gingival tissue thickness increased with every injection; there was no difference in gingival papillae loss between second and third collagen injections. CONCLUSIONS: The injectable form of atelocollagen is a promising material for gingival soft tissue regeneration and stimulation and allows for reduction in the number of procedures and support in a variety of surgical scenarios. This is a pilot study that clinically measures the impact of injected atelocollagen on periodontal tissue biotype, including the thickness of gingivae and gingival papillae regeneration.

Insulin resistance is associated with impaired olfactory function in adult patients with type 1 diabetes: A cross-sectional study.

AIM: To investigate whether insulin resistance is a predictor for decreased olfactory function in adult type 1 diabetes patients (T1DM). MATERIALS AND METHODS: The following parameters were examined in the group of 113 T1DM participants: body mass index (BMI), waist-hip ratio (WHR), TG/HDL ratio, glycated hemoglobin (HbA1c ), visceral fat (VF) in body bioimpedance, specific calculators (eGDR, VAI). Bilateral olfactory test score (BOTS) was performed using 12-odour-tests from Sniffin' Sticks. Then participants were allocated to one of two groups: normosmia (10-12 odours identified) or hyposmia/anosmia (0-9 odours). The association between BOTS and insulin resistance indicators was analyzed using: Spearman's rank correlation, multivariate linear regression analysis, and receiver operating characteristic (ROC) curve. RESULTS: 49.6% participants were diagnosed with hyposmia/anosmia, median BOTS was 10. BOTS correlated significantly with: WHR, TG, VF index, TG/HDL ratio, VAI, and eGDR. In multivariate linear regression analysis higher WHR turned out to be statistically significant independent predictor of lower BOTS (ß = -0.36; P = .005) after adjustment for age, sex, TG and peripheral neuropathy (R2 = 0.19; P = .0005). The ROC analysis indicated a WHR cut-off of 0.92 [area under the ROC curve (AUC): 0.737; 95% confidence interval (CI): 0.647-0.828, P < .0001] as the best among evaluated factors significantly affecting hyposmia/anosmia occurrence (sensitivity of this cut-off 0.50 and specificity 0.86). CONCLUSIONS: We have provided evidence of an association between lowered insulin sensitivity expressed in bioelectrical impedance analysis, anthropometrical (WHR), laboratory (TG/HDL ratio) measurements, specific calculators (eGDR, VAI) and deteriorated olfactory function.

Tobacco smoking decreases clinical symptoms of gingivitis in patients with type 1 diabetes-a cross-sectional study.

OBJECTIVE: Periodontal disease may develop on the background of microvascular complications of diabetes. However, some modifying factors, such as tobacco smoking, should be taken into consideration when assessing risk of development of chronic complications. The aim of the study was the clinical assessment of the periodontal status in patients with type 1 diabetes according to tobacco smoking. SUBJECTS AND METHODS: A total of 362 subjects aged 29 (IQR 22-35) years, type 1 diabetes duration 12 (8-18) years, hemoglobin A1c, HbA1c 8.0 (7.2-9.1)% were included. We used Gingival Index, Approximal Plaque Index, and Sulcus Bleeding Index to assess periodontal health. Patients were divided into two subgroups according to current cigarette smoking. RESULTS: No differences in age, diabetes duration, and chronic complications were found between subgroups. A better metabolic control of diabetes expressed by lower HbA1c (p = 0.00001) and triglyceride levels (p = 0.004) was shown in nonsmokers. Smokers presented significantly lower gingival bleeding, p = 0.009. HbA1c correlated with API in study group (Rs = 0.16; p = 0.002) and in nonsmokers subgroup (Rs = 0.2;p = 0.004), however, not in smoker's subgroup. In multivariable regression analysis, smoking cigarettes (ß = -0.26; p = 0.0002), hs-CRP (ß = 0.15; p = 0.03) and age (ß = -0.19; p = 0.007) occurred to be independent predictors of SBI after adjustment for confounding variables (R2  = 0.13; p = 0.001). CONCLUSIONS: Patients with type 1 diabetes smoking cigarettes presented lower gingival sulcus bleeding and worse metabolic control of diabetes than nonsmoking patients.

Association Between Self-reported Physical Activity and Skin Autofluorescence, a Marker of Tissue Accumulation of Advanced Glycation End Products in Adults With Type 1 Diabetes: A Cross-sectional Study.

PURPOSE: The accumulation of advanced glycation end products (AGEs) in local tissue is an important cause of low-grade inflammation and oxidative stress and is linked to late diabetic complications. Physical activity has various beneficial cardiometabolic effects in type 1 diabetes (T1D) and is associated with lower frequency of chronic complications of diabetes, although the specific mechanisms still remain unclear. The present study determines the association between self-reported physical activity and skin autofluorescence (AF), a marker of tissue accumulation of AGEs in adults with T1D. METHODS: We enrolled 119 patients (63 women), aged 34 years (interquartile range [IQR], 26-41 years), with T1D duration of 17 years (IQR, 12-25 years), glycosylated hemoglobin (HbA1c) of 7.9% (IQR, 7.1%-8.9%) referred to an outpatient diabetes clinic. Patients with diabetes duration of <5 years, age >65 years, concomitant diabetic ketoacidosis, and severe complications that restrict physical activity (eg, diabetic foot, diabetic proliferative retinopathy, blindness) were excluded. Physical activity was measured with the short version of the International Physical Activity Questionnaire (IPAQ-SF), and raw scores were then log-transformed because of non-normality. The accumulation of AGEs in the skin was assessed on the basis of skin AF. Correlations between AF and various laboratory and clinical findings were assessed, and multivariate linear regression analysis was used to examine factors that influenced AGEs. FINDINGS: Skin AF correlated positively with age (Spearman's coefficient [Rs] = 0.47; P < 0.0001), HbA1c (Rs = 0.30; P = 0.001), waist-to-hip ratio (WHR; Rs = 0.23; P = 0.02), and negatively with logIPAQ-SF (Rs = -0.28; P = 0.002). A stepwise multivariable linear regression analysis indicated age (ß = 0.46; P < 0.0001), HbA1c (ß = 0.21; P = 0.01), and logIPAQ-SF score (ß = -0.17; P = 0.04) as predictors of the skin AF after adjustment for sex and WHR (R2 = 0.36; P < 0.0001). IMPLICATIONS: Higher physical activity is related to lower accumulation of AGEs in patients with T1D. Our study provides new insight into the beneficial effects of physical activity in T1D according to tissue accumulation of AGEs.

Type 1 Diabetes and Periodontal Health.

It is well established that hyperglycemia affects periodontal outcomes. A body of evidence, predominantly over the past 20 years supports significant independent associations between periodontal disease and glycemic control or complications of diabetes. Association between periodontal tissue and hyperglycemia is possible through altered cellular immunity, increased proliferation of bacteria, microangiopathy, and formation of the advanced glycation end products. However, most studies focus solely on patients with type 2 diabetes or diabetes in general. There is still the paucity of data concerning patients with type 1 diabetes (T1D). Here, the authors consider the possible mechanisms linking periodontal disease with diabetes, focusing mainly on T1D and discuss possible diagnostic and therapeutic approaches.

Association of olfactory function with the intensity of self-reported physical activity in adults with type 1 diabetes.

INTRODUCTION    Olfactory function is impaired in patients with type 1 diabetes and can be recognized as a form of diabetic neuropathy. Physical activity has various beneficial effects on type 1 diabetes. OBJECTIVES    The aim of this study was to assess a relation between physical activity and olfactory function in patients with type 1 diabetes. PATIENTS AND METHODS    We enrolled 120 patients with type 1 diabetes referred to an outpatient diabetes clinic. Patients with diabetes duration of less than 5 years, age above 65 years, concomitant diabetic ketoacidosis, and those using drugs affecting nasal mucosa were excluded. The final study sample included 90 patients. A control group comprised 22 healthy participants. Olfactory function was assessed using 12 odor­emitting apens called Sniffin' Sticks. Physical activity was measured using the short version of the International Physical Activity Questionnaire (IPAQ­SF). RESULTS    There was a significant difference in the occurrence of hyposmia between diabetic patients and healthy controls (70.0% vs 45.5%, respectively; P = 0.03). There were no significant differences in IPAQ­SF results between the groups. Moreover, IPAQ­SF results correlated positively with olfactory test scores (r = 0.25; P = 0.02) and negatively with age. Additionally, patients with retinopathy and autonomic neuropathy obtained lower IPAQ­SF scores than patients without those complications. A stepwise multivariable linear regression analysis indicated IPAQ scores, body mass index, and peripheral neuropathy as predictors of the olfactory test score (R = 0.2).  CONCLUSIONS    Our study confirms the beneficial role of physical activity in type 1 diabetes within the structures of the central nervous system.

High-intensity Exercise in Men with Type 1 Diabetes and Mode of Insulin Therapy.

The purpose of this study was to evaluate the impact of high intensity exercise on glucose levels and risk of metabolic decompensation in males with type 1 diabetes (T1D), depending on the method of insulin administration. The study comprised 29 males (aged 25.3±5.1 years; duration of diabetes 10.3±3.2 years) treated with continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injections (MDI). Treadmill exercise test was performed twice in each patient until subjective exhaustion as maximum according to the Borg scale. All the patients achieved ≥85% of the maximal heart rate. Distance during the test was 4 500±1 400 m and 4 473±1 559 m in the MDI and CSII groups, respectively, which was achieved in 31±8 min. During the test and in the 6 h after, no clinically significant episodes of hypoglycemia occurred. Mean glucose levels did not exceed 10 mmol/L in most patients. The risk of the composite endpoint (hypoglycemia<3.8 mmol/L, hyperglycemia≥16.6 mmol/L, ketones≥0.6 mmol/L, and lactate>2.2 mmol/L) was higher in patients treated with MDI than CSII (OR3.75, 95%CI:1.22-11.52, p=0.02). In conclusion, planned high intensity physical effort in men with well-controlled T1D is metabolically safe. CSII shows greater metabolic advantage over MDI during and after high intensity exercise in men with T1D.

Impaired olfactory function is related to the presence of neuropathy in adults with type 1 diabetes.

INTRODUCTION: Olfactory dysfunction is suggested to be a clinical manifestation of central diabetic neuropathy. The aim of the study was to assess olfactory function in adult patients with type 1 diabetes. MATERIALS AND METHODS: A total of 106 patients with type 1 diabetes and 30 healthy subjects were included in the study. We evaluated the metabolic control of diabetes and the presence of chronic complications. Olfactory function was assessed with Sniffin' Sticks. RESULTS: We found a negative correlation between olfactory identification scores and body mass index ( Rs -0.2; p = 0.04) and triglycerides ( Rs = -0.2; p = 0.04). We showed lower olfactory identification scores in neuropathy group versus non-neuropathy group [8 (interquartile range, 7-9) vs 10 (interquartile range, 9-11) points; p = 0.005]. In multivariate linear regression, impaired olfaction was independently associated with neuropathy (beta, -0.3; p = 0.005). In multivariate logistic regression, diabetes duration (odds ratio, 1.06; 95% confidence interval, 1.00-1.11; p = 0.04) and olfactory identification score (odds ratio, 0.61; 95% confidence interval, 0.43-0.85; p = 0.003) were independently associated with neuropathy. CONCLUSION: Olfactory dysfunction is observed in patients with type 1 diabetes and diabetic peripheral neuropathy.

[The assessment of periodontal status in smoking and non-smoking patients with type 1 diabetes].

Chronic microvascular complications of type 1 diabetes relate to small and medium-sized vessels and clinically manifest as retinopathy, nephropathy and neuropathy as well as periodontitis. Cigarette smoking significantly modifies the course of inflammation in subjects without diabetes. The aim of the study was to assess the periodontal status in smoking and non-smoking subjects with type 1 diabetes. Materials and Methods: 115 subjects with type 1 diabetes, median age 32 years (IQR 25-38), median HbA1c 8.3% (7.4-9.4) were included. Assessed gingival indices comprised API, SBI, GI. Results: Smoking cigarettes was more frequent among men compared to women (p = 0.03). API was lower among women compared to men (p = 0.004). There was no correlation between HbA1c and gingival indexes, however, people achieving good metabolic control (HbA1c≤6.5%) had a lower API (p = 0.039). Smokers presented lower SBI compared to non- -smokers (p = 0.03). Conclusions: People with type 1 diabetes smoking cigarettes present lower gingival bleeding compared to non-smokers. In people with poor metabolic control of type 1 diabetes there is an increased accumulation of dental plaque in comparison with well-controlled type 1 diabetic patients.

[Diabetes mellitus and psychiatric diseases]. / Cukrzyca a choroby psychiczne.

Metabolic disorders, especially diabetes mellitus, occur more often in patients diagnosed with psychiatric diseases than in the general population. The suggested reasons include common environmental factors, like a lifestyle leading to obesity and insulin resistance, social and economic status. Moreover, these disorders partially share a common genetic background. The influence of antipsychotic therapy itself also plays an important role. An increased risk of metabolic disorders, like glucose dysregulation, dyslipidemia or weight gain, exists during antipsychotic treatment. These drugs influence the hypothalamic regions controlling food intake, impair the insulin release by beta cells or induce insulin resistance. Therefore the choice of antipsychotic drug should be dependent on the actual patient's metabolic status and his comorbidities. Patients treated with antipsychotics should be screened for several metabolic disorders. Periodic checks for abnormalities of body weight, waist circumference, blood glucose or lipid profile are recommended in these patients. Any abnormality noticed during such a check is the indication for antipsychotic treatment modification and adequate metabolic disorder treatment.