Design and rationale for the SIB trial: a randomized parallel comparison of semaglutide versus placebo on intestinal barrier function in type 2 diabetes mellitus.

Objective: To describe the rationale and design of the SIB trial, an interventional clinical trial testing the hypothesis that subcutaneous (s.c.) once-weekly semaglutide can improve intestinal permeability and reduce systemic inflammation in participants with type 2 diabetes (T2D) and obesity. Methods: SIB (NCT04979130) is an investigator-initiated, single-center randomized, double-blinded, placebo-controlled clinical study being conducted at the University of Colorado Anschutz Medical Campus. The primary objective of this novel trial is to test the hypothesis that subcutaneous (s.c.) once-weekly semaglutide could improve intestinal permeability and reduce systemic inflammation in participants with T2D and obesity. Eligible participants had a diagnosis of type 2 diabetes, elevated body mass index, and evidence of systemic inflammation. Participants were randomized 1:1 to s.c. semaglutide or placebo. Participants were assessed for intestinal permeability and markers of inflammation at baseline, mid-study, and at the end of the study. Efficacy assessments were based on the analysis of the following: lactulose:mannitol ratio test, serum lipopolysaccharide-binding protein (LBP), fecal calprotectin, inflammatory biomarkers (IL-6, TNF, IL-1, IL-8, hs-CRP), and HbA1c. All participants who enrolled in the trial provided written informed consent after having received written and oral information on the trial. The risks of semaglutide use were minimized by administration according to FDA-labeled use and close monitoring for adverse events. Discussion: SIB is the first study to examine the effects of GLP-1 receptor agonists on intestinal permeability in humans and will provide important data on their impact on systemic inflammation and intestinal permeability in the setting of T2D and obesity.

Should metformin remain the first-line therapy for treatment of type 2 diabetes?

Metformin is a biguanide that is used as first-line treatment of type 2 diabetes mellitus and is effective as monotherapy and in combination with other glucose-lowering medications. It is generally well-tolerated with minimal side effects and is affordable. Although the safety and efficacy of metformin have been well-established, there is discussion regarding whether metformin should continue to be the first choice for therapy as other anti-hyperglycemic medications exhibit additional advantages in certain populations. Despite a long-standing history of metformin use, there are limited cardiovascular outcomes data for metformin. Furthermore, the available studies fail to provide strong evidence due to either small sample size or short duration. Recent data from glucagon-like peptide-1 receptor agonist and sodium-glucose cotransporter-2 inhibitor cardiovascular and renal outcomes trials demonstrated additional protection from diabetes complications for some high-risk patients, which has impacted the guidelines for diabetes management. Post-hoc analyses comparing hazard ratios for participants taking metformin at baseline versus not taking metformin are inconclusive for these two groups. There are no data to suggest that metformin should not be initiated soon after the diagnosis of diabetes. Furthermore, the initiation of newer glycemic-lowering medications with cardiovascular benefits should be considered in high-risk patients regardless of glycemic control or target HbA1c. However, cost remains a major factor in determining appropriate treatment.

Comparative evaluation of adjunctive antibiotics given post periodontal flap surgery.

BACKGROUND: Antibiotics are known to improve clinical parameters in patients with periodontitis, so they should be capable of enhancing the surgical treatment outcome by improving clinical parameters when given adjunctively following periodontal flap surgery. METHODS: Thirty subjects with moderate to severe periodontitis were randomly divided into three groups: Group I: 10 patients without antibiotic prescription after flap surgery, Group II: 10 patients prescribed with metronidazole 400 mg t.i.d. for 14 days, and Group III: 10 patients prescribed with doxycycline 200 mg o.d. as booster dose followed by successive doses of 100 mg o.d. for 21 days. Plaque index (PI), gingival index (GI), pocket probing depth (PPD), and clinical attachment level (CAL) were recorded at baseline, 2 weeks, and 2 months. The mean values and standard deviation values for each parameter were calculated using analysis of variance. Group comparison was done using paired t-and unpaired t-tests. RESULTS: Reduction in PI, GI, PPD, and CAL after 2 weeks and 3 months from baseline in all the three groups was seen; intergroup comparison showed more reduction in PPD and GI and more gain in CAL in Groups II and III after 3 months when compared with Group I. No statistical difference was seen between Groups II and III. CONCLUSION: Within the limits of this study, it can be concluded that antibiotic administration as an adjunct to conventional flap surgery helps in improving clinical parameters.

Effect of nonsurgical periodontal therapy on thyroid stimulating hormone in hypothyroid patients with periodontal diseases.

BACKGROUND: The endocrine and the immune system demonstrate a mutual relationship under pathophysiologic conditions. Thyroid hormone plays an important role in the regulation of normal growth and development. Although there is proven bidirectional influence of systemic diseases on periodontium, there are fewer studies on the effect of periodontal therapy on the hormone levels. This study aims to assess the effect of nonsurgical periodontal therapy (NSPT) on serum thyroid stimulating hormone (TSH) levels in hypothyroid patients with periodontal diseases. MATERIALS AND METHODS: A total of 30 randomly chosen subjects of which 15 known hypothyroidism patients (13 females and 2 males) who were under medication for the same and 15 healthy individuals were enrolled into the study. Clinical parameters and serum TSH levels were recorded at baseline in both the groups, whereas TSH levels were recorded again at 3 months after NSPT in hypothyroid patients. Intergroup comparison was carried out by Tukey Kramer multiple comparisons test and the difference in variables was analyzed using one-way analysis of variance. RESULTS: Mean values of TSH in hypothyroid patients 3.48 ± 1.41 µIU/ml showed significant reduction to 2.31 ± 1.24 µIU/ml (P ≤ 0.05) at 3 months follow up of NSPT. Clinical parameters improved significantly in both the groups after NSPT (P ≤ 0.05). Alveolar bone loss was greater in hypothyroid patients than the control group at baseline. CONCLUSION: NSPT plays a major role in improving periodontal conditions by reducing inflammatory markers and thereby influencing the thyroid hormone. Thus, immune system serves as an important link between thyroid dysfunction and periodontal diseases.

Comparison of serum erythropoietin levels in smokers and nonsmokers with periodontitis: A biochemical study.

AIMS: This study was carried out to compare serum erythropoietin (Epo) levels in smokers and nonsmokers with periodontitis. MATERIALS AND METHODS: Fifty-one subjects of both sexes (age range: 30-65 years) with chronic periodontitis (CP) participated in this study. Seventeen patients with generalized CP, nonsmokers without anemia were included in Group I (control group), 17 patients with generalized CP, nonsmokers with anemia were included in Group II, and 17 patients who were smokers, having generalized CP were included in Group III. Peripheral blood samples were obtained and assessed for the number of erythrocytes (total red blood cell [TRBC]), hemoglobin (Hb), and Epo levels. STATISTICAL ANALYSIS USED: One-way analysis of variance and Tukey-Kramer multiple comparisons test to assess the statistical difference between groups. RESULTS: Epo levels varied considerably between the 3 groups. Highest values of Epo were seen in Group III with mean Epo value = 42.81 ± 15, followed by Group II Epo value = 35.21 ± 10.9, then Group I Epo value = 22.06 ± 4.19. Smokers in Group III with CP showed more prevalence toward higher values of Hb% (mean Hb = 12.06 ± 0.84) while there was no statistical difference in the values of TRBC values among the 3 groups (Group I TRBC value = 3.87 ± 0.38, Group II TRBC value = 4.01 ± 0.83, and Group III TRBC value = 3.88 ± 0.45). CONCLUSION: Periodontitis patients were seen to have lower Epo values further strengthening the hypothesis that CP may lead to anemia of chronic disease. In smokers, higher Hb values were seen with higher Epo levels. It indicates that periodontitis individually and along with smoking may affect anemic status of smokers. Thus, Epo levels may be better means to assess anemic status of smokers than relying only on Hb values.

Non-familial cherubism: A case report with its surgical management.

Cherubism is an autosomal-dominant inherited syndrome; it starts in early childhood and involutes by puberty. It is characterized by excessive bone degradation of the jaws and development of fibrous tissue masses. Non-familial cherubism is a rare entity, which needs to be documented. This paper describes the findings of non-familial cherubism. An 11-year-old male patient reported with bilateral swellings of the jaws and unerupted teeth. Extensive gingival overgrowth, cherubic facial appearance, multilocular osteolytic lesions in radiographs and family history lead to the diagnosis of non-familial cherubism. Treatment included full mouth excision of the gingival tissue by gingivectomy with both manual instrumentation and electrosurgery. Patient is being monitored and recalled for frequent follow-ups. Dental practitioners need to be alert with patients presenting with gingival overgrowth.