Controlled Type 2 Diabetes Mellitus Patients Research Articles

Serum tumor markers: Can they clinically implicate in type 2 diabetes mellitus?

“Serum tumor markers expression (CA19-9, CA242, and CEA) and its clinical implications in type 2 diabetes mellitus” authored by Meng and Shi presents an observational case-control study investigating the correlation between tumor markers and type 2 diabetes mellitus (T2DM). The study explores the diagnostic accuracy of tumor markers, particularly cancer antigen 19-9 (CA19-9), CA242, and carcinoembryonic antigen, in poorly controlled T2DM patients with hemoglobin A1c levels exceeding 9%, employing receiver operating characteristic curve analysis. Though study offers valuable insights into the potential utility of tumor markers in clinical practice, caution is advised regarding routine tumor marker testing due to challenges such as limited availability and cost. Additionally, the study overlooks potential confounding factors like smoking and alcohol consumption. Variations in CA19-9 and CA242 expression underscore the complex interplay between tumor markers and systemic diseases, warranting further investigation into their diagnostic and prognostic implications. While Meng and Shi represent a significant contribution to the field, more extensive research is needed to fully elucidate the role of tumor markers in diabetes management and beyond.

Effects of prediabetes and type 2 diabetes on cognitive functions.

We aimed to investigate the effect of glycemic impairment in prediabetes on cognitive impairment and the impact of glycemic control on cognitive function in patients with diabetes. This age- and sex-matched case-control study included a total of 80 individuals: 20 patients with prediabetes, 20 patients with well-controlled type 2 diabetes mellitus (T2DM) (HbA1C < %7.5), 20 patients with poorly controlled T2DM (HbA1C >% 7.5), and 20 healthy controls. The poorly controlled T2DM patients performed significantly worse than controls and patients with prediabetes in the verbal memory process test (p = 0.041). In Trail Making Test B, the well-controlled and poorly-controlled groups with diabetes performed significantly worse (p = 0.015) than patients with prediabetes and controls, and in the Wisconsin Card Sorting Test (WCST), all three patient groups performed significantly worse (p = 0.007) than controls. T2DM causes early brain aging and declines cognitive functions since the prediabetic stage. Poor glycemic control in T2DM patients contributes to cognitive impairments, especially in learning.

Serum Activities of Ferritin Among Controlled and Uncontrolled Type 2 Diabetes Mellitus Patients.

BackgroundDiabetes mellitus (DM) is a metabolic disorder characterized by the cells' inefficient utilization of blood glucose. DM occurs in two types: type 1 DM (T1DM) and type 2 DM (T2DM). DM results in increased blood sugar levels attributed to the non-functioning of the insulin-producing islet cells of the pancreas (type 1 DM) and insulin resistance, among other causes. Despite the initiation of treatment, in some people, diabetes remains uncontrolled and, over some time, could cause damage to other organs of the body, including the eyes, heart, and kidneys, among others. Recently, it was observed that iron metabolism and increased activity of serum ferritin (hyperferritinemia) could influence the development of T2DM. This study aims to assess the activities of ferritin among controlled and uncontrolled T2DM patients and compare them with the control group who were non-diabetic.MethodsThe study included 30 controlled and uncontrolled T2DM patients and an equal number of controls. The study was conducted between September and October 2021, and all patients included were those attending the General Medicine outpatient department attached to the RVM Institute of Medical Sciences and Research Centre, Siddipet, Telangana, South India. Blood glucose activities were estimated by the glucose oxidase-peroxidase (GOD-POD) method using the Randox Daytona plus analyzer, and serum ferritin was measured by the chemiluminescence method using the Beckmann Coulter Access 2 instrument.ResultsThe mean age of the cases and the controls was 56.5 years and 46.7 years, respectively. Serum ferritin activities among people with controlled diabetes (73.3±56.6 ng/ml) (p=0.0003) and uncontrolled diabetes (269.8±347.1 ng/ml) (p=0.0006) varied significantly as compared to the controls (40.853±15.55). Glucose activities among controls (82.9±7.4 mg/dl), controlled T2DM patients (120.9±28.6 mg/dl), and uncontrolled T2DM patients (316.06±145.41 mg/dl) also showed significant differences.ConclusionHyperferritinemia is evident among uncontrolled T2DM patients. However, increased serum ferritin activities were also noted among controlled T2DM patients as compared to normal activities observed in the non-diabetic control group.

Comparison of Efficacy of Glimepiride, Alogliptin, and Alogliptin-Pioglitazone as the Initial Periods of Therapy in Patients with Poorly Controlled Type 2 Diabetes Mellitus: An Open-Label, Multicenter, Randomized, Controlled Study.

BackgroundThe choice of an optimal oral hypoglycemic agent in the initial treatment periods for type 2 diabetes mellitus (T2DM) patients remains difficult and deliberate. We compared the efficacy and safety of glimepiride (GLIM), alogliptin (ALO), and alogliptin-pioglitazone (ALO-PIO) in poorly controlled T2DM patients with drug-naïve or metformin failure.MethodsIn this three-arm, multicenter, open-label, randomized, controlled trial, poorly controlled T2DM patients were randomized to receive GLIM (n=35), ALO (n=31), or ALO-PIO (n=33) therapy for 24 weeks. The primary endpoint was change in the mean glycosylated hemoglobin (HbA1c) levels at week 24 from baseline. Secondary endpoints were changes in HbA1c level at week 12 from baseline, fasting plasma glucose (FPG) levels, lipid profiles at weeks 12 and 24, and parameters of glycemic variability, assessed by continuous glucose monitoring for 24 weeks.ResultsAt weeks 12 and 24, the ALO-PIO group showed significant reduction in HbA1c levels compared to the ALO group (–0.96%±0.17% vs. –0.37%±0.17% at week 12; –1.13%±0.19% vs. –0.18%±0.2% at week 24). The ALO-PIO therapy caused greater reduction in FPG levels and significant increase in high-density lipoprotein cholesterol levels at weeks 12 and 24 than the ALO therapy. Compared to low-dose GLIM therapy, ALO-PIO therapy showed greater improvement in glycemic variability. The adverse events were similar among the three arms.ConclusionALO-PIO combination therapy during the early period exerts better glycemic control than ALO monotherapy and excellency in glycemic variability than low-dose sulfonylurea therapy in uncontrolled, drug-naïve or metformin failed T2DM patients.

Adjunctive Er:YAG laser in non-surgical periodontal therapy of patients with inadequately controlled type 2 diabetes mellitus: A split-mouth randomized controlled study.

Limited studies are available comparing the outcomes of non-surgical periodontal therapy (NSPT) with or without adjunctive Er:YAG laser (ERL) in patients with type 2 diabetes mellitus (T2DM). This study evaluated the effects of ERL adjunctive NSPT on single-rooted teeth of inadequately controlled T2DM patients with periodontitis. Twenty-two inadequately controlled T2DM participants with periodontitis were recruited. Adopting a double-blinded split-mouth design and under block randomization, we investigated the effects of ERL in calculus removal then degranulation mode, or a sham treatment, adjunct NSPT, which included two visits of full-mouth root surface debridement delivered within 4-10days, to test or control single-rooted teeth (Wuxi Stomatology Hospital, trial 2017-016). We followed periodontal parameters (plaque %, bleeding on probing [BOP] %, probing pocket depth [PPD], probing attachment level [PAL]) and selected systemic parameters (fasting plasma glucose [FPG], glycosylated hemoglobin [HbA1c%], high sensitivity C-reactive protein) at baseline, one, three, and six months after periodontal treatment. The study was completed as planned. Periodontal parameters, FPG and HbA1c% of the 22 participants appeared significantly improved at six months (p < 0.001). The 44 ERL treated, compared to 44sham treated single-rooted teeth exhibited significant improvement in BOP, mean PPD, and mean PAL at various postoperative follow-up time points (effect size ≥0.44; p < 0.001). No adverse event was reported. Periodontal treatment outcomes in the T2DM patients with inadequate glycemic control were better in the single-rooted teeth received ERL adjunct NSPT. Further studies are warranted to confirm the observations reported in this short-term clinical study.

Vascular effects following intensification of glycemic control in poorly controlled patients with long-standing type 2 diabetes mellitus.

The aim of the present study was to investigate the effect of intensive antidiabetic therapy on vascular indices in type 2 diabetes mellitus (T2DM) patients. Poorly controlled T2DM patients (n = 62, mean age 64years, T2DM duration 14years, HbA1c ≥ 7.5%) were studied at baseline and following intensive treatment to achieve optimal glycemic control. Brachial artery flow-mediated dilation, carotid-femoral pulse wave velocity, central augmentation index, large and small (C2) artery compliance, carotid intima-media thickness (cIMT), and ankle-brachial index were assessed at baseline and follow-up. HbA1c decreased from 8.8% (8.1, 10.1) (median, interquartile range-IQ) to 7.4% (6.9, 7.8), p < 0.001. Triglycerides and high-sensitivity C-reactive protein levels were decreased by ~ 10% and 50%, respectively (p < 0.05). Maximum cIMT and C2 increased at follow-up (0.97 ± 0.25 to 1.03 ± 0.27mm and 3.3 (2.7, 4.2) to 4.2 (3.2, 5.4) ml/mmHg × 10, respectively, p < 0.05). In subgroup analysis, the observed changes in vascular indices were not affected by diabetes duration, presence of cardiovascular disease, or insulin treatment. In patients with long-standing T2DM, short-term aggressive glycemic control was associated with an improvement of microvascular function (C2) and deterioration of carotid atherosclerosis (IMT) without any effect on the elastic properties of large arteries.

211-OR: Differential Cerebral Blood Flow in Controlled and Uncontrolled Patients with Type 2 Diabetes Mellitus

Introduction: Patients with type 2 diabetes mellitus (T2DM) show variable brain tissue changes and mood and cognitive symptoms, which may result from altered cerebral blood flow (CBF). However, the regional CBF status in controlled and uncontrolled T2DM patients remains unclear, which can be examined with arterial spin labeling (ASL) imaging. Our aim was to examine regional CBF between controlled and uncontrolled T2DM patients using ASL imaging procedures. Methods: We collected hemoglobin A1c (A1C) data and 3D pseudo-continuous ASL data from 32 T2DM patients (16 controlled [A1C &amp;lt; 7%], age, 56.5±6.5 years; BMI, 29.6±6.2 kg/m2; 8 female; 16 uncontrolled [A1C ≥ 7%], age, 57.6±7.5 years; BMI, 30.0±5.1 kg/m2; 11 female) using a 3.0-Tesla MRI. A1C was measured by point-of-care testing. Whole-brain CBF maps were calculated, normalized to a common space, smoothed, and compared between groups (controlled T2DM patients vs. uncontrolled T2DM patients) using analysis of covariance (SPM12; covariates, age and sex; p&amp;lt;0.05). Results: No significant differences in age or sex appeared between groups. Multiple brain areas showed decreased CBF values in the cingulate, caudate, putamen, insula, hippocampus, amygdala, thalamus, hypothalamus, midbrain, cerebellum, prefrontal and frontal, and temporal cortices in uncontrolled T2DM patients over controlled T2DM patients. However, few brain sites in controlled T2DM patients, including the cerebellum, pons, medulla, parahippocampal gyrus, and temporal cortices showed reduced CBF over uncontrolled T2DM patients. Conclusion: Uncontrolled T2DM patients show significant reduction in CBF compared to controlled T2DM in areas that are involved in mood and cognition regulation. The findings suggest that uncontrolled levels may contribute to reduce regional CBF leading to site-specific tissue changes resulting to mood and cognition deficits in the condition. Disclosure S. E. Choi: None. B. Roy: None. M. Freeby: Research Support; Self; Abbott Diabetes, Novo Nordisk Inc. R. Kumar: None. Funding National Institutes of Health (1R01NR017190-03, 3R01NR017190-03S1)

Plasminogen Activator Inhibitor-1 in poorly controlled vs well controlled Type-2 Diabetes Mellitus patients: A case-control study in a district hospital in Ghana.

Hypofibrinolysis resulting from the up-regulation of plasminogen activator inhibitor-1 (PAI-1) usually occurs in patients with type 2 diabetes mellitus (T2DM), rendering them hypercoagulable. This study assessed the plasma antigen and activity levels of the PAI-1 enzyme in T2DM patients in a district hospital in Ghana. This was a hospital-based case-control study conducted from December 2018 to May 2019 at Nkenkaasu District Hospital. Sixty subjects with T2DM (30 T2DM subjects with good glycemic control and 30 with poor glycemic control), and 30 apparently healthy blood donors were recruited into the study. Blood specimens were collected for complete blood count, lipid profile, PAI-1 Ag and PAI-1 activity levels. A pre-tested questionnaire was used to obtain demographic and clinical information. The data was analyzed using SPSS version 22.0. Elevated PAI-1 Ag and activity levels were observed in the T2DM subjects compared to the healthy controls, with the levels and activity significantly higher (PAI-1 Ag; p< 0.001, PAI-1 activity level; p = 0.004) in the T2DM subjects with poor glycemic control in comparison to those with good glycemic control. A significant positive correlation was observed between HbA1c and PAI-1 enzymes. PAI-1 Ag levels significantly increased along with increased total cholesterol (Β = 0.262, p = 0.033), triglyceride (Β = -0.273, p = 0.034) and HbA1c (Β = 0.419, p = 0.001). Similarly, PAI-1 activity level was associated with total cholesterol (Β = 0.325, p = 0.009), triglyceride (Β = -0.262, p = 0.042), HbA1c (Β = 0.389, p = 0.003) and VLDL-c (Β = -0.227, p = 0.029). PAI-1 antigen/activity is enhanced in poorly controlled Ghanaian T2DM subjects. The hypercoagulable state of the affected individuals put them at higher risk of developing cardiovascular diseases. Good glycemic control to regulate plasma PAI-1 levels is essential during T2DM lifelong management. Markers of fibrinolysis should be assessed in these individuals and appropriate anticoagulants given to prevent thrombosis and adverse cardiovascular diseases.

Systemic conditions of diabetic patients diagnosed with apical periodontitis

ABSTRACT Objective: This study aimed to evaluate the association between glycemic control status in type 2 diabetes mellitus (T2DM) patients and apical periodontitis. Methods: Twenty-seven patients were involved in this study. The survey was based on anamnesis, intra and extra oral examination and radiographic evaluation. Diabetes mellitus information involved type of diabetes and blood glucose analysis. Patients were divided according to their metabolic control status (glycemic controlled and poorly controlled T2DM patients). Results: A higher fasting blood glucose level (p = 0.004) and a higher percentage of HbA1c (p = 0.0001) were demonstrated in poorly controlled T2DM patients when compared to glycemic controlled T2DM. However, the frequency of apical periodontitis and the elapsed time since diabetes mellitus diagnosis were higher in controlled T2DM patients, reaching 64%. Nevertheless, controlled T2DM patients presented a higher number of apical periodontitis cases (p &lt; 0.05). Findings support that controlled patients T2DM presented higher presence of apical periodontitis than poorly controlled T2DM ones. In these patients, the time elapsed since the diagnosis was higher, which may have provided a longer period of oscillation and/or uncontrolled metabolism. Conclusions: Therefore, it might contribute to the development and maintenance of apical periodontitis in glycemic controlled patients of this study.

553-P: Brain Microstructural Tissue Changes in Patients with Controlled and Uncontrolled Type 2 Diabetes

Patients with type 2 diabetes mellitus (T2DM) show brain tissue changes in mood and cognitive control sites. However, it is unclear whether brain microstructural tissue changes differ between patients with controlled (hemoglobin A1c [A1C] &amp;lt;7%) and uncontrolled (A1C ≥ 7%) T2DM. Diffusion tensor imaging (DTI) based mean diffusivity (MD) measures water molecular motion within tissue and shows microstructural changes by values reduced in acute and increased in chronic pathological conditions. Methods: We collected DTI and A1C data from 37 T2DM patients (15 controlled; age 56.4±6.8 years, BMI 29.2±6.2 kg/m2, diabetes duration 6.0±4.8 years, A1C 6.2±0.4%, 7 female; 22 uncontrolled; age 57.2±7.4 years, BMI 30.5±5.1 kg/m2, diabetes duration 15.0±9.0 years, A1C 8.2±1.3%, 14 female) and 12 healthy controls (age 54.3±8.2 years, BMI 25.9±4.6 kg/m2, A1C 5.2±0.4%, 5 male) using a 3.0-Tesla magnetic resonance imaging scanner and point-of-care A1C testing. Whole-brain MD maps were calculated, normalized to a common space, smoothed, and compared between groups (controlled T2DM patients vs. healthy controls; uncontrolled T2DM patients vs. healthy controls) using ANCOVA (SPM12; covariates, age and sex; uncorrected threshold, p&amp;lt;0.005). Results: No significant differences appeared between groups in age or sex. Mean duration of diabetes was significantly different between controlled and uncontrolled T2DM patients (p &amp;lt;0.001). Uncontrolled T2DM patients showed increased MD values in multiple brain areas, including the cingulate, insula, para-hippocampal, hippocampus, cerebellum, basal-forebrain, prefrontal, frontal, and temporal cortices over controlled T2DM patients and healthy controls. Conclusion: Uncontrolled T2DM patients show widespread chronic brain microstructural changes in areas that are involved in mood and cognition regulation. The findings support tight glycemic control to prevent further brain tissue damages in patients with T2DM. Disclosure S.E. Choi: None. B. Roy: None. M. Freeby: Research Support; Self; Abbott, Novo Nordisk Inc. M.A. Woo: None. R. Kumar: None. Funding National Institutes of Health (R01NR017190)

Comparative evaluation of biphasic insulin with metformin and triple oral hypoglycemic agents (OHA) in type 2 diabetes patients

IntroductionThe prevalence of secondary failure to oral hypoglycemic agents among type 2 diabetes mellitus (T2DM) patients ranges from 30 to 60%. The alternative approaches to overcome this issue are either switching to triple oral hypoglycemic agents (OHA) or intensifying the regimen by adding insulin. ObjectiveTo compare the glycemic control achieved with biphasic insulin plus metformin and triple OHA in T2DM patients who were not adequately controlled with two OHA regimen. MethodsA qualitative prospective study was conducted at Asir diabetes center, Abha, KSA. Poorly controlled T2DM patients with two OHA for at least 1 year with glycated hemoglobin (HbA1c) >7.0% were included. Subjects were divided into group I (a third OHA was added to the existing two OHA regimen) and group II (switched over to Biphasic insulin and metformin). At baseline and 3-month intervals, level of HbA1C, Fasting Plasma Glucose (FPG), Postprandial Plasma Glucose (PPG), Blood Pressure (BP), lipid profile and hypoglycemic episodes were obtained and evaluated for one year. Results41.1% of patients were in group I and 58.9% were in group II. At the end of the study, there was a significant reduction in HbA1c in group II subjects comparing to group I (8.18 ± 1.32 vs 8.79 ± 1.81, p = 0.0238). FPG and PPG were improved also in group II. The mean body weight increased from baseline in group II is +4.48 kg and decreased from baseline in group I (−0.46 kg). 11.3% from group I and 23.7% from group II reported hypoglycaemic incidences. ConclusionBiphasic insulin and metformin regimen could be an appropriate therapeutic option for achieving good glycemic control compared with triple OHA in patients with two OHA failure.

Serum Levels of Carbamylated LDL, Nitrotyrosine and Soluble Lectin-like Oxidized Low-density Lipoprotein Receptor-1 in Poorly Controlled Type 2 Diabetes Mellitus.

Carbamylated low-density lipoprotein (cLDL) has profound proatherogenic properties. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been identified as the primary cLDL receptor. The soluble form of LOX-1 (sLOX-1) and 3-nitrotyrosine (NT) have recently been suggested as biomarkers of vascular disease. Although type 2 diabetes mellitus (T2DM) is characterised by an increased atherosclerotic risk, the clinical data on cLDL, NT and sLOX-1 levels in T2DM are limited. To explore the possible role of cLDL, NT and sLOX-1 as potential biomarkers for disease progression and complications in poorly controlled T2DM patients with and without microalbuminuria. The serum concentrations of cLDL, NT and sLOX-1 were measured by ELISA in a cross-sectional study of 60 T2DM patients and 35 nondiabetic controls. Both the normoalbuminuric (n = 34) and the microalbuminuric (n = 26) patients had significantly higher serum levels of cLDL and NT than the healthy controls, but sLOX-1 was only elevated in the microalbuminuric subgroup (p < 0.05). Carbamylated LDL correlated positively with NT in the diabetic subjects (rs = 0.266, p = 0.04) while it correlated with urea only in the control group (rs = 0.475, p = 0.004). The serum concentration of sLOX-1 correlated significantly with fasting glucose (rs = 0.441, p < 0.001), HbA1c (rs = 0.328, p = 0.01) and microalbuminuria (rs = 0.272, p = 0.035) in the whole diabetic cohort. The present study highlights the potential of cLDL, NT and sLOX-1 as possible markers of diabetic complications.

The Number and Potency of Endothelial Progenitor Cells in Type 2 Diabetes Mellitus Patients

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a metabolic disease, due to the disorder of insulin function, insulin secretion, or both. Long-term hyperglycemia conditions promote endothelial dysfunction precedes to the development of multiple organ dysfunctions. Endothelial progenitor cells (EPCs) and hematopoietic stem cell (HSCs) are the key cellular effectors of postnatal neovascularization and play central role in endothelial dysfunction. However, in T2DM condition, the number of apoptotic HSCs increase, it may cause the reduction in potency and number of EPCs. In diabetes, the circulating EPCs number decrease and their functionality is impaired, but mechanism underlie of this impairement is unknown. The purpose of this study was to examine the relationship duration diabetes with the number and potency of EPC cells in T2DM patients controlled and poorly controlled.METHODS: Thirty-eight T2DM male patients were classified into two group based on Indonesian Society of Endocrinology/Perkumpulan Endokrinologi Indonesia (PERKENI) criteria on T2DM. The first group was a controlled glycemic condition group (hemoglobin A1c (HbA1C) &lt;7.0%) and the second group was a poorly controlled glycemic condition group (HbA1C &gt;7.0%). Cluster of differentiation (CD)34+ and CD133+ expressions were used as specific marker for EPC, while quantified bright aldehyde dehydrogenase (ALDHbr) assay was used to represented the potency of EPCs.RESULTS: This study showed that in poorly controlled T2DM group the number of EPCs was lower by 24.80% (p&lt;0.05) compared to the T2DM controlled group. Similarly, the expression of ALDHbr was lower by 43.07% (p&lt;0.05) in poorly controlled group.CONCLUSION: There was a decrease in the number and potency of EPCs in poorly controlled T2DM patients compared to the controlled T2DM patients. There was also a strong negative correlation between the duration of diabetes and number of EPCs.KEYWORDS: ALDHbr, endothelial progenitor cells, type 2 diabetes mellitus

Current status of dental implants survival and peri-implant bone loss in patients with uncontrolled type-2 diabetes mellitus.

The current review summarizes recent evidence on the impact of type-2 diabetes mellitus (T2DM) on implant dentistry, highlighting the behavior of peri-implant bone. There is no definitive information on the development and course of peri-implant bone loss associated with T2DM; however, poorly controlled T2DM patients present worse outcomes. Nevertheless, dental implants may be a successful therapy for these patients in a manner similar to healthy individuals, when glycemic levels and oral hygiene are strictly maintained. The most recent literature on the impact of T2DM on peri-implant bone loss was reviewed to evaluate the feasibility of dental implant therapy over the time for these patients.

Local and systemic level of adipokines as markers of inflammation in periodontitis and type 2 diabetes mellitus after periodontal therapy

Objective Periodontal disease and diabetes mellitus are common disorders connected mainly by inflammation. While exploring and analyzing the several pathways linking diabetes and periodontitis, adipokines were prominent candidates amongst the biochemical parameters that could elucidate this interrelation. Therefore, the present investigation was conducted to evaluate the effect of nonsurgical periodontal treatment on the glycemic control of well-controlled patients with type 2 diabetes mellitus (T2DM) and chronic periodontitis (CP), as well as on the serum and GCF levels of visfatin, chemerin and adiponectin in systemically healthy subjects with CP, controlled T2DM patients with CP. Patients and methods Serum and GCF samples were collected at baseline and 3 months after therapy to evaluate levels of visfatin, chemerin and adiponectin using enzyme linked immunosorbent assay in all study groups. Group I: 15 healthy individuals. Group II: 30 CP patients. Group III: 30 periodontitis patients with T2DM. Results Significant reduction in serum and GCF levels of both chemerin and visfatin were recorded 3 months after therapy in periodontitis groups. On the contrary, significant elevation of serum and GCF levels of adiponectin were found. There was a direct positive correlation between percent change in serum glycosylated haemoglobin A1c level and serum visfatin and chemerin level and a negative correlation with serum adiponectin level. Conclusion This study demonstrates that serum and GCF levels of chemerin, visfatin and adiponectin play a crucial role in the pathogenesis of periodontitis and diabetes and reinforce the positive effect of periodontal therapy on the glycemic control.

Therapeutic Effect of Quadruple Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus Who Have Insulin Limitations

Background: Insulin therapy is the treatment of choice in type 2 diabetes mellitus (T2DM) patients who are not achieving glycemic goals despite triple oral hypoglycemic agent (OHA) combination therapy. However, there is still no additional treatment option for patients who cannot afford insulin therapy or who have various clinical limitations. The purpose of this study was to evaluate the clinical efficacy and safety of four OHA combination therapy in poorly controlled T2DM patients who could not afford insulin therapy. Methods: Forty-seven T2DM patients were enrolled according to the following criteria: 1) glycosylated hemoglobin [HbA1c] > 8.5%, 2) ongoing treatment with 3 OHA combination therapy (metformin, sulfonylurea, dipeptidyl peptidase-4 inhibitor), or 3) combined limitations for applying insulin therapy. Patients were given the fourth OHA (pioglitazone) in addition to their previous treatment for 12 months. We evaluated changes in HbA1c, body weight, hypoglycemic events, and side effects. Results: At study completion, mean HbA1c and fasting plasma glucose were significantly reduced from 9.6% to 8.04% and from 198.4 mg/dL to 161.5 mg/dL, respectively (P < 0.001). Mean body weight was significantly increased from 66.7 kg to 69.3 kg. Hypoglycemia and side effects were observed 18 times and only 3 cases showed abnormal liver function tests or edema. In addition, subjects with higher initial HbA1c levels and HOMA-beta showed an independent association with a greater reduction in HbA1c. Conclusion: The 4 OHA combination therapy is effective and safe when insulin is not feasible.

Glimepiride as Add-on Therapy in Type 2 Diabetic Patients with Metformin Monotherapy: A Real-Life Study from Egypt

AbstractBackground: Adding glimepiride to metformin mono-therapy was reported to improve the glycemic status of patients with type 2 diabetes mellitus (T2DM), with tolerable safety profile.Aim of Work: The present real-life study aimed to inves-tigate the safety and effectiveness of glimepiride add-on therapy in poorly controlled T2DM patients with metformin monotherapy.Patients and Methods: In the present prospective study, we included 1050 poorly controlled T2DM patients from Egypt, and for whom the investigators decided to prescribe glimepiride in addition to metformin. Glimepiride was added to patients uncontrolled on metformin monotherapy for at least three months despite reaching the maximally tolerated dose. Regimen doses were decided by the investigators to reflect the in-practice approach. We followed the included patients for at three months and safety outcomes were measured throughout the study period.Results: After three months of treatment, the mean HbA1c level decreased by 1.54% (95% CI: –1.61 to –1.46%), with a mean percentage reduction of 16.3% (p<0.001). In addition, 31.7% of the included patients achieved the targeted HbA1c level <7%. The total number of adverse events was 15 adverse events occurred in 11 patients. Ten episodes of non-serious hypoglycemia were recorded.Conclusion: The present real-life study confirms the efficacy of glimepiride add-on therapy to metformin mono-therapy among poorly controlled T2DM patients from Egypt. Moreover, glimepiride/metformin regimen exhibits well-tolerable safety profile.

Crestal Bone Loss Around Submerged and Non-Submerged Dental Implants in Individuals with Type-2 Diabetes Mellitus: A 7-Year Prospective Clinical Study

Objective: In establishing an evidence-based rationale for the optimal use of implant therapy in patients with type 2 diabetes mellitus (T2DM), it is essential to first understand the impact of glycemic control on early healing and the success of dental implants. The objective of this study was to evaluate crestal bone loss (CBL) and stability around submerged and non-submerged dental implants in Saudi patients with well- and poorly controlled T2DM. Subject and Methods: Thirty-five patients with well-controlled T2DM (24 males and 11 females) and 32 poorly controlled T2DM patients (19 males and 13 females) were included. CBL was measured on digital radiographs; resonance frequency analysis (RFA) measurements were made for each implant at the time of fixture placement and at 3 months in both the groups. A p value less than 0.05 was considered statistically significant. Results: A total of 124 dental implants were placed. Mean RFA values between baseline and 3 months in poorly controlled T2DM patients was statistically significant (p = 0.048). CBL at first year (p = 0.047), second year (p = 0.041), third year (p = 0.046), and seventh year (p = 0.035) was significantly worse in poorly controlled T2DM. CBL around non-submerged dental implants showed statistically significant differences at all time-intervals (p < 0.05). Conclusion: Poorly controlled T2DM patients present worse peri-implant bone outcomes as compared to patients with well-controlled T2DM. We suggest that the predictability of successful dental implant therapy outcomes depends on the maintenance of optimal haemoglobin A1c levels.

Plasma levels of free fatty acids correlate with type 2 diabetes mellitus.

Free fatty acids (FFA) mediate adverse metabolic effects such as downregulated carbohydrate metabolisms, providing causal links between obesity and the development of type 2 diabetes mellitus (T2DM). Here, we investigated the plasma concentrations of FFA alone and in combination with protein glycation as potential diagnostic and prognostic biomarkers of T2DM. EDTA-plasma obtained from 48 newly diagnosed male T2DM patients, 48 long-term controlled (24 male and 24 female) T2DM patients, 20 prediabetic male T2DM patients and two age-matched control cohorts (48 non-diabetic (ND) men; 24 male and 24 female ND partipants) were analysed for a set of clinical parameters including FFA. Glycation sites were quantified after tryptic digestion using tandem mass spectrometry. Median plasma concentrations of FFA were almost three-fold higher in samples obtained from newly diagnosed (long-term controlled) T2DM patients than in those obtained from the control group, providing diagnostic sensitivity (SN) of 92% (85%) and specificity (SP) of 90% (88%). When combined with the glycation level of lysine-141 of haptoglobin, diagnostic accuracy improved further for newly diagnosed (SN, 94%; SP 96%) and long-term controlled (SN, 85%; SP, 94%) T2DM patients (HbA1c: SN, 88%; SP, 96%). A prospective pilot study evaluating the prognostic value revealed initially low FFA levels for pre-diabetic patients that increased in the following four years in patients whose prediabetic state worsened or who developed T2DM. FFA levels are elevated in newly diagnosed and long-term controlled T2DM patients, providing high diagnostic accuracy of 87% and 91%, respectively, which improved further when combined with the glycation degree of lysine-141 in haptoglobin. Additionally, FFA showed higher mean fold-changes than HbA1c or FPG in subjects developing T2DM, indicating higher sensitivity towards the progression of the disease.

Comparison of non-insulin antidiabetic agents as an add-on drug to insulin therapy in type 2 diabetes: a network meta-analysis

We aimed to evaluate the comparative efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), or thiazolidinedione (TZD) as an adjunctive treatment in patients with poorly controlled type 2 diabetes mellitus (T2DM) on insulin therapy. We searched Medline, Embase, the Cochrane Library, and ClinicalTrials.gov through April 2016. Bayesian network meta-analyses were performed with covariate adjustment. The primary outcome was the change in glycated hemoglobin A1c (HbA1c) from baseline. Fifty randomized controlled trials covering 15,494 patients were included. GLP-1RA showed the greatest HbA1c-lowering effect compared to the control (−0.84%; 95% credible interval, −1.00% to −0.69%), followed by TZD (−0.73%; −0.93 to −0.52%), SGLT2i (−0.66%; −0.84% to −0.48%), and DPP4i (−0.54%; −0.68% to −0.39%). SGLT2i showed the greatest fasting plasma glucose reduction. GLP-1RA and SGLT2i showed greater body weight reduction, whereas TZD increased body weight. TZD was ranked the highest in terms of insulin dose reduction. The risk of hypoglycemia was increased with TZD or GLP-1RA. The study provides the best available evidence on the comparative efficacy and safety of non-insulin anti-diabetic agents on top of pre-existing insulin therapy for inadequately controlled T2DM patients.