Project description:IntroductionIrisin is a unique myokine with striking effects on regulating insulin sensitivity and energy metabolism. This study aimed to investigate the changes in serum irisin in patients with newly diagnosed type 2 diabetes mellitus (T2DM) following sitagliptin treatment.MethodsThirty-two patients with T2DM were treated with 100 mg/day sitagliptin for 16 weeks. Twenty age-, sex- and body mass index (BMI)-matched healthy subjects were enrolled as the control group. Irisin and metabolic parameters were measured at baseline and after treatment.ResultsPatients with T2DM had lower irisin levels than the controls (10.03 ± 2.06 vs. 13.06 ± 3.10 ng/ml, P < 0.01). Sitagliptin treatment significantly increased serum irisin levels in T2DM patients compared to baseline (11.18 ± 1.91 vs. 10.03 ± 2.06 ng/ml, P < 0.01). Increased irisin levels were associated with decreased fasting blood glucose (FBG) (β = - 0.24, P < 0.05) and glycosylated hemoglobin (HbA1c) (β = - 0.15, P < 0.05).ConclusionsSitagliptin treatment significantly increased serum irisin levels in patients with T2DM, and the increase of the irisin level was associated with decreases of FBG and HbA1c levels. These results suggest that irisin might be involved in the antidiabetic mechanisms of sitagliptin.Trial registrationClinicalTrials.gov identifier NCT04495881.
Project description:This study aimed to examine the effect of a diabetes pay-for-performance (P4P) program on all-cause mortality in patients with newly diagnosed type 2 diabetes mellitus. Using a Taiwanese representative nationwide cohort, we recruited 5478 patients with newly diagnosed type 2 diabetes enrolled in the P4P program within 5 years after a diagnosis of diabetes between January 1, 2002 and December 31, 2010 and individuals not enrolled in the P4P program were recruited as the control group matched 1:1 with the study group. We used multivariate Cox proportional hazard models analysis to investigate the effect of the P4P program and adherence on all-cause mortality. A total of 250 patients died in the P4P group compared to 395 in the control group (mortality rate 104 vs 169 per 10,000 person-years, respectively, P < .0001). The control group also had more comorbidities. Patients enrolled in the P4P program demonstrated significant long-term survival benefits, of which the adjusted hazard ratio (aHR) for all-cause mortality was 0.58 [95% CI (0.48-0.69)]. In the study group, better adherence to the P4P program resulted in a greater reduction in mortality, with aHRs [95% CI] of 0.48 [0.38-0.62] and 0.36 [0.26-0.49] in subjects with a minimum 1-year and 2-year good P4P adherence, respectively. Participating in the P4P program within 5 years after the diagnosis of diabetes resulted in a significant reduction in all-cause mortality, and this effect was particularly pronounced in the patients with better adherence to the P4P program.
Project description:Rationale: Sleep-disordered breathing (SDB) is associated with increased risk of adverse pregnancy outcomes, including gestational diabetes mellitus (GDM). GDM is a significant cause of maternal and infant morbidities. Assessing these risk factors concurrently may facilitate both the identification of women at GDM risk and the initiation of GDM prevention strategies.Objectives: To investigate whether SDB events, including SDB in rapid eye movement (REM) sleep and other sleep parameters, are associated with increased risk of GDM and to evaluate the performance of the models investigating associations between breathing and sleep parameters and GDM risk.Methods: In this case-control study, 46 women with newly diagnosed GDM and 46 healthy control subjects, who were individually matched for age, gestational age, body mass index, race, and parity, completed overnight polysomnographic studies and sleep questionnaires after being screened for GDM during the late-second to mid-third trimesters. Conditional logistic regression analysis was used to identify models investigating associations between risk factors and GDM risk. The Bayesian information criterion (BIC) was employed to compare models; the model with the lowest BIC is preferred.Results: Obstructive sleep apnea (OSA; defined as an apnea-hypopnea index [AHI] >5 events/h) was present in 22% of subjects with GDM and 9% of control subjects (P < 0.001). Women with OSA had a higher GDM risk (odds ratio [OR], 4.71; 95% confidence interval [CI], 1.05-21.04). In individual models, GDM risk was also significantly higher among women with higher overall AHI (events/h OR, 1.81; 95% CI, 1.01-3.27), higher AHI in REM (events/h OR, 2.09; 95% CI, 1.02-4.31), higher oxygen desaturation index greater than or equal to 4% (ODI4; events/h OR, 2.21; 95% CI, 1.03-4.73), and higher Sleep Apnea Symptom Score (OR, 2.72; 95% CI, 1.11-6.69). The percentage of non-REM sleep was significantly associated with decreased risk of GDM (percentage of non-REM sleep OR, 0.88; 95% CI, 0.78-0.99). The BIC supports the conclusion that there is a strong association between AHI in REM and GDM risk compared with the other significant models.Conclusions: SDB events, including REM-related OSA, are linked to increased GDM risk. GDM risk is also influenced by intercorrelated sleep variables.
Project description:Six oral medication classes have been approved by the Food and Drug Administration for the treatment of type 2 diabetes. Although all of these agents effectively lower blood glucose, the evidence supporting their impact on other clinical events is variable. There also are substantial cost differences between agents. We aimed to evaluate temporal trends in the use of specific drugs for the initial management of type 2 diabetes and to estimate the economic consequences of non-recommended care.We studied a cohort of 254,973 patients, aged 18 to 100 years, who were newly initiated on oral hypoglycemic monotherapy between January 1, 2006, and December 31, 2008, by using prescription claims data from a large pharmacy benefit manager. Linear regression models were used to assess whether medication initiation patterns changed over time. Multivariate logistic regression models were constructed to identify independent predictors of receiving initial therapy with metformin. We then measured the economic consequences of prescribing patterns by drug class for both patients and the insurer.Over the course of the study period, the proportion of patients initially treated with metformin increased from 51% to 65%, whereas those receiving sulfonylureas decreased from 26% to 18% (P<.001 for both). There was a significant decline in the use of thiazolidinediones (20.1%-8.3%, P<.001) and an increase in prescriptions for dipeptidyl peptidase-4 inhibitors (0.4%-7.3%, P<.001). Younger patients, women, and patients receiving drug benefits through Medicare were least likely to initiate treatment with metformin. Combined patient and insurer spending for patients who were initiated on alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, or dipeptidyl peptidase-4 inhibitors was $677 over a 6-month period compared with $116 and $118 for patients initiated on metformin or a sulfonylurea, respectively, a cost difference of approximately $1120 annually per patient.Approximately 35% of patients initiating an oral hypoglycemic drug did not receive recommended initial therapy with metformin. These practice patterns also have substantial implications for health care spending.
Project description:BackgroundThe negative impact of diabetes mellitus is well recognized, yet little is known about the effect of this disease on the liver, an organ susceptible to nonalcoholic fatty liver disease related to insulin resistance. We evaluated whether adults with newly diagnosed diabetes were at increased risk of serious liver disease.MethodsWe used administrative health databases for the province of Ontario (1994-2006) to perform a population-based matched retrospective cohort study. The exposed group comprised 438 069 adults with newly diagnosed diabetes. The unexposed comparison group--those without known diabetes--consisted of 2 059 708 individuals, matched 5:1 to exposed persons, by birth year, sex and local health region. We excluded individuals with pre-existing liver or alcohol-related disease. The primary study outcome was the subsequent development of serious liver disease, namely, liver cirrhosis, liver failure and its sequelae, or receipt of a liver transplant.ResultsThe incidence rate of serious liver disease was 8.19 per 10 000 person-years among those with newly diagnosed diabetes and 4.17 per 10 000 person-years among those without diabetes. The unadjusted hazard ratio was 1.92 (95% confidence interval [CI] 1.83-2.01). After adjustment for age, income, urban residence, health care utilization and pre-existing hypertension, dyslipidemia, obesity and cardiovascular disease, the hazard ratio was 1.77 (95% CI 1.68-1.86).InterpretationAdults with newly diagnosed diabetes appeared to be at higher risk of advanced liver disease, also known as diabetic hepatopathy. Whether this reflects nonalcoholic fatty liver disease or direct glycemic injury of the liver remains to be determined.
Project description:There is growing evidence that diabetes mellitus (DM) is an important risk factor for tuberculosis (TB). A significant number of DM patients have poor glycemic control. This study was carried out to find the impact of poor glycemic control on newly diagnosed smear-positive pulmonary tuberculosis patients with type-2 diabetes mellitus in a tertiary care hospital.In a hospital-based prospective study, newly diagnosed smear-positive pulmonary TB with DM patients were classified as poorly controlled diabetes (HBA1C?7%) and optimal control diabetics (HbA1c<7%). Patients were started on anti-TB treatment and followed for 2 years for severity and treatment outcome. ANOVA was used for numerical variables in the univariable analysis. Logistic regression analysis was used for multivariable analysis of treatment outcome. The significance level was kept at a P?0.05.A total of 630 individuals who met the inclusion criteria were analyzed; of which 423 patients had poor glycemic control (PGC) and 207 patients had optimal glycemic control (OGC). The average HbA1c was 10±2.6 and 5±1.50 in the PGC and OGC groups, respectively. The mean symptom score was significantly higher in the PGC group compared with patients in the OGC group (4.55±0.80 vs. 2.70±0.82, P<0.001). PGC was associated with more extensive lung disease, lung cavitation, and positive sputum smear at the baseline. In PGC, sputum smears were significantly more likely to remain positive after 2 months of treatment. PGC patients had significantly higher rates of treatment failure (adj. OR 0.72, 95% CI 0.58-0.74, P<0.001) and relapse (adj. OR 2.83, 95% CI 2.60-2.92, P<0.001).Poor glycemic control is associated with an increased risk of advanced and more severe TB disease in the form of lung cavitations, positive sputum smear, and slower smear conversion. It has a profound negative effect on treatment completion, cure, and relapse rates in patients with pulmonary tuberculosis.
Project description:Early identification of individuals with elevated risk of developing diabetes mellitus, followed by the implementation of effective prevention interventions can delay the onset of the disease and related complications. In this regard, recent studies have shown that miRNAs are useful as early markers of certain disease types, including diabetes. We used high throughput sequencing to assess miRNA expression profiles from whole blood of 12 individuals with screen-detected diabetes, 12 with prediabetes and 12 with normal glucose tolerance, matched for age, blood pressure, smoking and body mass index. We identified a total of 261 (57 novel) differentially expressed miRNA profiles between the study groups. Comparison of the miRNA expression profiles between prediabetess and diabetes revealed 25 common miRNA, but highlighted some interesting differences. For instance, three miRNAs (miR-126-3p, miR-28-3p miR-486-5p) were dysregulated in prediabetes compared to screen-detected diabetes. Target gene analysis showed thousands of potential genes and KEGG pathway analysis revealed 107 significant pathways of which some are involved signal transduction, cell-cell communications, cell growth and death, immune response, endocrine system and metabolic diseases. This first detailed African study has shown both known and novel differentially expressed miRNAs in relation to glucose tolerance.
Project description:PurposeLittle is known about the relationship between brain-derived neurotrophic factor (BDNF) gene polymorphisms and psychiatric symptoms in diabetes patients. We investigated the effects of BDNF Val/66/Met polymorphism, glucose status, psychological susceptibility, and resilience on anxiety and depression symptoms in patients newly diagnosed with type 2 diabetes mellitus (T2DM).Materials and methodsWe examined biochemical factors and BDNF polymorphism in 89 patients who were newly diagnosed with T2DM. Psychiatric symptoms were investigated with the Hospital Anxiety and Depression Scale (HADS), and the Connor-Davidson Resilience Scale (CD-RISC) and Impact of Event Scale (IES) were used to assess psychological resilience and susceptibility to psychological distress, respectively. Logistic regression analyses were conducted to investigate factors associated with psychiatric symptoms.ResultsWe determined that 62 patients (70%) were Met-carriers. No significant differences were found between the Val/Val homozygous and Met-carrier groups regarding age, sex, body mass index, and clinical factors related to glycemic control and lipid profiles. HADS-anxiety and HADS-depression scores and IES factor scores were higher in the Met-carrier than the Val/Val homozygous group. Hemoglobin A1c (HbA1c) level was significantly inversely correlated with the severity of depressive symptoms. Resilience factors showed significant inverse correlations, and IES factors showed positive correlations with depressive symptom severity. In the logistic regression analysis model, depressive symptoms were significantly associated with HbA1c and BDNF polymorphism, whereas only the hyperarousal factor of the IES scale was associated with anxiety.ConclusionDepressive symptoms are associated with the presence of the Met-carriers and lower HbA1c in patients newly diagnosed with T2DM.
Project description:BACKGROUND: Genetic variability of the major subunit (CACNA1E) of the voltage-dependent Ca(2+) channel Ca(V)2.3 is associated to risk of type 2 diabetes, insulin resistance and impaired insulin secretion in nondiabetic subjects. The aim of the study was to test whether CACNA1E common variability affects beta cell function and/or insulin sensitivity in patients with newly diagnosed type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: In 595 GAD-negative, drug naïve patients (mean ± SD; age: 58.5 ± 10.2 yrs; BMI: 29.9 ± 5 kg/m(2), HbA1c: 7.0±1.3) with newly diagnosed type 2 diabetes we: 1. genotyped 10 tag SNPs in CACNA1E region reportedly covering ?93% of CACNA1E common variability: rs558994, rs679931, rs2184945, rs10797728, rs3905011, rs12071300, rs175338, rs3753737, rs2253388 and rs4652679; 2. assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp and beta cell function by state-of-art modelling of glucose/C-peptide curves during OGTT. Five CACNA1E tag SNPs (rs10797728, rs175338, rs2184945, rs3905011 and rs4652679) were associated with specific aspects of beta cell function (p<0.05-0.01). Both major alleles of rs2184945 and rs3905011 were each (p<0.01 and p<0.005, respectively) associated to reduced proportional control with a demonstrable additive effect (p<0.005). In contrast, only the major allele of rs2253388 was related weakly to more severe insulin resistance (p<0.05). CONCLUSIONS/SIGNIFICANCE: In patients with newly diagnosed type 2 diabetes CACNA1E common variability is strongly associated to beta cell function. Genotyping CACNA1E might be of help to infer the beta cell functional phenotype and to select a personalized treatment.
Project description:AimsWe investigated quantitative expression, mutual aggregation and relation with hyperglycemia of insulin resistance (IR) and beta-cell dysfunction (BCD) in newly diagnosed type 2 diabetes.MethodsWe assessed IR with euglycemic hyperinsulinemic clamp and BCD with modelled glucose/C-peptide response to oral glucose in 729 mostly drug-naïve patients. We measured glycated hemoglobin, pre-prandial, post-prandial and meal-related excursion of blood glucose.ResultsIR was found in 87.8% [95% confidence intervals 85.4-90.2] and BCD in 90.0% [87.8-92.2] of subjects, ranging from mild to moderate or severe. Approximately 20% of subjects had solely one defect: BCD 10.8% [8.6-13.1] or IR 8.6% [6.6-10.7]. Insulin resistance and BCD aggregated in most subjects (79.1% [76.2-82.1]). We arbitrarily set nine possible combinations of mild, moderate or severe IR and mild, moderate or severe BCD, finding that each had a similar frequency (∼10%). In multiple regression analyses parameters of glucose control were related more strongly with BCD than with IR.ConclusionsIn newly-diagnosed type 2 diabetes, IR and BCD are very common with a wide range of expression but no specific pattern of aggregation. Beta-cell dysfunction is likely to play a greater quantitative role than IR in causing/sustaining hyperglycemia in newly-diagnosed type 2 diabetes.