The Type 2 Deiodinase Thr92Ala Polymorphism Is Associated with Worse Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.
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SUBMITTER: Zhang X
PROVIDER: S-EPMC5061950 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Genetic factors play critical roles in the onset and progression of obesity. Brown adipose tissue (BAT) activity is also critical for adiposity. The objective of this study was to evaluate the prevalence and effects of BAT gene polymorphisms in pediatric obesity. This case-control study included 270 non-obese and 86 obese children. All participants underwent genotyping for type 2 deiodinase (DIO2) Thr92Ala (rs225014). The prevalence of the homozygous Ala/Ala allele of the DIO2 gene in the obese group was 15.1% versus 6.3% in the non-obese group, resulting in an odds ratio (OR) of 3.393 (p = 0.003). The results of this study indicate that the homozygous Ala/Ala allele of the DIO2 gene is associated with an increased risk of pediatric obesity and suggest that pediatric obesity might be suitable for assessing the association with gene polymorphisms related to BAT, especially DIO2 Thr92Ala.
| S-EPMC9600981 | biostudies-literature
Project description:Background Type 2 deiodinase (Dio2) is a selenoenzyme that is mainly expressed in the endoplasmic reticulum of the central nervous system, brown adipose tissue, and placenta and is responsible for outer ring deiodination of thyroxine (T4) to form biologically active triiodothyronine (T3). The Thr92Ala polymorphism of Dio2 has been found to be a potential risk factor for various diseases beyond the hypothalamus-pituitary-thyroid (HPT) axis. Methods We searched the relevant studies in the PubMed, Embase, and Cochrane Library databases and Google Scholar. A systematic review and meta-analysis of studies on the Thr92Ala polymorphism and metabolic parameters beyond the HPT axis (e.g., BMI, fasting glycemic traits, plasma lipid levels, and hypertension risk) were performed. Results Six eligible studies that analyzed the relationship between the Thr92Ala polymorphism and metabolic parameters beyond the thyroid were identified. All selected studies excluded patients with thyroid dysfunction, and diabetic patients were also excluded when fasting glucose and fasting insulin levels were meta-analyzed. The Thr92Ala polymorphism was found to be a significant risk factor for higher BMI (Std. mean difference 0.31 (0.01, 0.60), p = 0.04) and higher fasting glucose levels (Std. mean difference 1.18 (0.05, 2.31), p = 0.04). However, fasting insulin levels, plasma lipid levels, and hypertension risk showed a nonsignificant association with the Thr92Ala polymorphism. Conclusion Compared with euthyroid noncarriers (Thr/Thr), euthyroid Ala92-Dio2 carriers showed increased BMI levels, and Ala92-Dio2 carriers also had higher fasting plasma glucose levels than matched euthyroid nondiabetic noncarriers.
| S-EPMC8516525 | biostudies-literature
Project description:Background: Type 2 Deiodinase (DIO2) converts thyroxine (T4) into the active hormone triiodothyronine (T3). Thr92Ala DIO2 polymorphism has been associated with reduced conversion of T4 into T3 and central nervous system hypothyroidism. However, how Thr92Ala DIO2 polymorphism affects cognitive function is still unclear. Objective: To assess the association between Thr92Ala DIO2 polymorphism and cognitive performance in older adults. Design: Cross-sectional study. Setting: University-based tertiary hospital in Brazil. Patients: > 65-year-old with no limiting clinical disease. Interventions: All participants answered a standard questionnaire before undergoing thyroid function laboratory evaluation and genotyping of the Thr92Ala DIO2 polymorphism. Main Outcomes: Cognitive impairment measured by the Word List Memory task from the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery (CERAD-NB) and the Brief Cognitive Screening Battery (BCSB). Results: A hundred individuals were included. Clinical and laboratory characteristics were similar among DIO2 genotypes (all p > 0.05). No differences were found in the Word List Memory, recall, or recognition tests of the CERAD-NB assuming a recessive model for the Ala/Ala vs. Thr/Ala-Thr/Thr genotypes. Results of Clock Drawing Test, Animal Fluency Test, Mini-Mental State Exam, and Figure Memory Test of the BCSB were similar between groups. Conclusions: These findings suggest that Thr92Ala DIO2 polymorphism is not associated with relevant cognitive impairment in older adults.
| S-EPMC9144704 | biostudies-literature
Project description:Diabetes mellitus and thyroid disorders are common endocrinopathies, which often occur parallel. Dyslipidemia is very common in both of these conditions. The development of hypothyroidism is well-known in type 1 diabetics, but it was not distinctly understood in type 2 diabetics. Thus we tried to examine the association between type II deiodinase (D2 or DIO2) Thr92Ala single nucleotide gene polymorphism and thyroid function among type 2 diabetes mellitus patients. A total of 130 type 2 diabetics were screened and genotyped for DIO2 Thr92Ala polymorphism. Fasting plasma glucose, Glycosylated haemoglobin, lipid and thyroid profiles, malondialdehyde (MDA) and paraoxonase were estimated according to standard procedures. A significant altered level of thyroid hormones (TH's) was found in Ala/Ala genotype when compared with Thr/Thr or Thr/Ala genotype. DIO2 and T3:T4 ratio significantly decreased, whereas total T4 and thyroid stimulating hormone levels significantly elevated among Ala/Ala genotype (131 ± 30 ng/ml; 0.12 ± 0.05; 7.17 ± 2.05 µg/dl; 4.77 ± 3.1 µIU/ml, respectively) when compared with Thr/Thr + Thr/Ala genotypes (176 ± 33 ng/ml; 0.21 ± 0.05; 5.21 ± 1.1 µg/dl; 2.59 ± 1.61 µIU/ml respectively). Moreover, D2 levels were significantly negatively correlated with TH's levels except total T4 among Ala/Ala genotypes. All the patients were having a poor glycemic control, and their glycemic status was positively correlating with MDA levels. On the other hand, serum paraoxonase activity decreased among Ala/Ala genotype (104 ± 21 vs. 118 ± 18 nmol/min/ml). In conclusion, DIO2 Ala92 homozygous variant found to be associated with altered levels of DIO2, Thyroid profile and paraoxonase. Hence, we recommend to do detail study of genetic factors related to thyroid function and prevent additional diabetic complications.
| S-EPMC4820430 | biostudies-literature
Project description:BackgroundSeveral studies have reported that clinical practice guidelines (CPGs) in a variety of clinical areas are of modest or variable quality. The objective of this study was to evaluate the quality of an international cohort of CPGs that provide recommendations on pharmaceutical management of glycemic control in patients with type 2 diabetes mellitus (DM2).Methods and findingsWe searched the National Guideline Clearinghouse (NGC) on February 15th and June 4th, 2012 for CPGs meeting inclusion criteria. Two independent assessors rated the quality of each CPG using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. Twenty-four guidelines were evaluated, and most had high scores for clarity and presentation. However, scope and purpose, stakeholder involvement, rigor of development, and applicability domains varied considerably. The majority of guidelines scored low on editorial independence, and only seven CPGs were based on an underlying systematic review of the evidence.ConclusionsThe overall quality of CPGs for glycemic control in DM2 is moderate, but there is substantial variability among quality domains within and across guidelines. Guideline users need to be aware of this variability and carefully appraise and select the guidelines that they apply to patient care.
| S-EPMC3618153 | biostudies-literature
Project description:BackgroundThe overall evidence base of anti-inflammatory therapies in patients with type 2 diabetes mellitus (T2DM) has not been systematically evaluated. The purpose of this study was to assess the effects of anti-inflammatory therapies on glycemic control in patients with T2DM.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched up to 21 September 2022 for randomized controlled trials (RCTs) with anti-inflammatory therapies targeting the proinflammatory cytokines, cytokine receptors, and inflammation-associated nuclear transcription factors in the pathogenic processes of diabetes, such as interleukin-1β (IL-1β), interleukin-1β receptor (IL-1βR), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB). We synthesized data using mean difference (MD) and 95% confidence interval (CI). Heterogeneity between studies was assessed by I2 tests. Sensitivity and subgroup analyses were also conducted.ResultsWe included 16 RCTs comprising 3729 subjects in the meta-analyses. Anti-inflammatory therapies can significantly reduce the level of fasting plasma glucose (FPG) (MD = - 10.04; 95% CI: -17.69, - 2.40; P = 0.01), glycated haemoglobin (HbA1c) (MD = - 0.37; 95% CI: - 0.51, - 0.23; P < 0.00001), and C-reactive protein (CRP) (MD = - 1.05; 95% CI: - 1.50, - 0.60; P < 0.00001) compared with control, and therapies targeting IL-1β in combination with TNF-α have better effects on T2DM than targeting IL-1β or TNF-α alone. Subgroup analyses suggested that patients with short duration of T2DM may benefit more from anti-inflammatory therapies.ConclusionOur meta-analyses indicate that anti-inflammatory therapies targeting the pathogenic processes of diabetes can significantly reduce the level of FPG, HbA1c, and CRP in patients with T2DM.
| S-EPMC10014557 | biostudies-literature
Project description:Diabetes mellitus (DM) is the ninth leading cause of death worldwide. Mortality from DM is largely attributed to disease complications. Glycemic control of DM patients reduces mortality. Studies indicated that the lack of glycemic control in DM patients could be influenced by the genetic background of the patients. Evidence suggests that adiponectin levels are dysregulated in DM patients with poor glycemic control. Serum adiponectin level is a heritable trait influenced by single nucleotide polymorphisms (SNPs) in the ADIPOQ gene. It is hypothesized that SNPs in ADIPOQ could modify glycemic control in DM patients. To test this hypothesis, 375 type 2 DM (T2DM) patients were recruited. Patients were classified into good vs. poor glycemic control according to hemoglobin A1c levels. Study subjects were genotyped for variations of four SNPs in ADIPOQ (rs17300539, rs266729, rs2241766, and rs1501299). Adiponectin levels were measured from the serum. Our analysis showed that reduced serum adiponectin, a longer duration of treatment, and increased insulin resistance were all significant predictors of poor glycemic control. Moreover, the T allele and the TT genotype of rs2241766 were significantly more frequent in patients with poor glycemic control (P < 0.05). Individuals with the TT genotype of rs2241766 had significantly lower levels of serum adiponectin (P < 0.05). It was concluded that lower levels of serum adiponectin and the T allele of rs2241766 SNP in ADIPOQ were associated with poor glycemic control in T2DM patients.
| S-EPMC9068336 | biostudies-literature
Project description:Long-term durable glycemic control is a difficult goal in the management of type 2 diabetes mellitus (T2DM). We evaluated the factors associated with durable glycemic control in a real clinical setting.We retrospectively reviewed the medical records of 194 new-onset, drug-naïve patients with T2DM who were diagnosed between January 2011 and March 2013, and were followed up for >2 years. Glycemic durability was defined as the maintenance of optimal glycemic control (glycosylated hemoglobin [HbA1c] <7.0%) for 2 years without substitution or adding other glucose-lowering agents. Clinical factors and glycemic markers associated with glycemic durability were compared between two groups: a durability group and a non-durability group.Patients in the durability group had a higher baseline body mass index (26.1 kg/m² vs. 24.9 kg/m²) and lower HbA1c (8.6% vs. 9.7%) than the non-durability group. The initial choice of glucose-lowering agents was similar in both groups, except for insulin and sulfonylureas, which were more frequently prescribed in the non-durability group. In multiple logistic regression analyses, higher levels of education, physical activity, and homeostasis model assessment of ?-cell function (HOMA-?) were associated with glycemic durability. Notably, lower HbA1c (<7.0%) at baseline and first follow-up were significantly associated with glycemic durability (adjusted odds ratio [OR], 7.48; 95% confidence interval [CI], 2.51 to 22.3) (adjusted OR, 9.27; 95% CI, 1.62 to 53.1, respectively), after adjusting for confounding variables including the types of glucose-lowering agents.Early achievement of HbA1c level within the glycemic target was a determinant of long-term glycemic durability in new-onset T2DM, as were higher levels of education, physical activity, and HOMA-?.
| S-EPMC5583406 | biostudies-other
Project description:BackgroundVeterans with evidence of homelessness have high rates of mental health and substance abuse disorders, but chronic medical conditions such as diabetes are also prevalent.ObjectiveWe aimed to determine the impact of homelessness on glycemic control in patients with type 2 diabetes mellitus.DesignLongitudinal analysis of a retrospective cohort.SubjectsA national cohort of 1,263,906 Veterans with type 2 diabetes. Subjects with evidence of homelessness were identified using a combination of diagnostic and administrative codes.Main measuresOdds for poor glycemic control using hemoglobin A1C (HbA1C) cutoff values of 8 % and 9 %. Homeless defined as a score based on the number of indicator variables for homelessness within a veterans chart.Key resultsVeterans with evidence of homelessness had a significantly greater annual mean HbA1C?? 8 (32.6 % vs. 20.43 %) and HbA1C?? 9 (21.4 % vs. 9.9 %), tended to be younger (58 vs. 67 years), were more likely to be non-Hispanic black (39.1 %), divorced (43 %) or never married (34 %), to be urban dwelling (88.8 %), and to have comorbid substance abuse (46.7 %), depression (42.3 %), psychoses (39.7 %), liver disease (18.8 %), and fluid/electrolyte disorders (20.4 %), relative to non-homeless veterans (all p?<?0.0001). Homelessness was modeled as an ordinal variable that scored the number of times a homelessness indicator was found in the Veterans medical record. We observed a significant interaction between homelessness and race/ethnicity on the odds of poor glycemic control. Homelessness, across all racial-ethnic groups, was associated with increased odds of uncontrolled diabetes at a cut-point of 8 % and 9 % for hemoglobin A1C ; however, the magnitude of the association was greater in non-Hispanic whites [8 %, OR 1.55 (1.47;1.63)] and Hispanics [8 %, OR 2.11 (1.78;2.51)] than in non-Hispanic blacks [8 %, OR 1.22 (1.15;1.28)].ConclusionsHomelessness is a significant risk factor for uncontrolled diabetes in Veterans, especially among non-Hispanic white and Hispanic patients. While efforts to engage homeless patients in primary care services have had some success in recent years, these data suggest that broader efforts targeting management of diabetes and other chronic medical conditions remain warranted.
| S-EPMC5071286 | biostudies-literature
Project description:Type 2 diabetes mellitus (DM) is a major cardiovascular (CV) risk factor and, as such, is considered a coronary artery disease risk equivalent. Although glycemic control is associated with decreased CV events epidemiologically, many prospective clinical trials have failed to conclusively demonstrate that aggressive glycemic control improves the CV prognosis of patients with type 2 DM, especially those with long-standing DM. Many therapies for type 2 DM with widely divergent mechanisms of action are available. Some of these drugs, in addition to their glucose-lowering actions, have properties that may reduce or increase CV events. Agents that lower both insulin resistance and postprandial hyperglycemia while at the same time avoiding hypoglycemia may be beneficial for CV health. This article reviews the evidence regarding the use of these agents and appropriate glycemic control targets for improving the adverse CV prognosis associated with type 2 DM. We conducted a systematic review of English articles using MEDLINE and the Cochrane Controlled Trials Register (1970-2010) using the following search terms: cardiovascular disease, randomized trials, hypoglycemia, and insulin resistance.
| S-EPMC3031437 | biostudies-literature