Impact Of Poor Glycemic Control Research Articles

The causal effect of HbA1c on white matter brain aging by two-sample Mendelian randomization analysis.

Poor glycemic control with elevated levels of hemoglobin A1c (HbA1c) is associated with increased risk of cognitive impairment, with potentially varying effects between sexes. However, the causal impact of poor glycemic control on white matter brain aging in men and women is uncertain. We used two nonoverlapping data sets from UK Biobank cohort: gene-outcome group (with neuroimaging data, (N = 15,193; males/females: 7,101/8,092)) and gene-exposure group (without neuroimaging data, (N = 279,011; males/females: 122,638/156,373)). HbA1c was considered the exposure and adjusted "brain age gap" (BAG) was calculated on fractional anisotropy (FA) obtained from brain imaging as the outcome, thereby representing the difference between predicted and chronological age. The causal effects of HbA1c on adjusted BAG were studied using the generalized inverse variance weighted (gen-IVW) and other sensitivity analysis methods, including Mendelian randomization (MR)-weighted median, MR-pleiotropy residual sum and outlier, MR-using mixture models, and leave-one-out analysis. We found that for every 6.75 mmol/mol increase in HbA1c, there was an increase of 0.49 (95% CI = 0.24, 0.74; p-value = 1.30 × 10-4) years in adjusted BAG. Subgroup analyses by sex and age revealed significant causal effects of HbA1c on adjusted BAG, specifically among men aged 60-73 (p-value = 2.37 × 10-8). Poor glycemic control has a significant causal effect on brain aging, and is most pronounced among older men aged 60-73 years, which provides insights between glycemic control and the susceptibility to age-related neurodegenerative diseases.

FRI606 Changes In The Pedal Microcirculation Of Diabetic Patients With Poor Glycemic Control Detected Using Non Invasive Optical Imaging

Abstract Disclosure: I.K. Bolakale-Rufai: None. S. French: None. J.C. Arias: None. K. Concha-Moore: None. T. Tan: None. D.G. Armstrong: None. A. Mazhar: Employee; Self; Modulim. C.C. Weinkauf: None. Background: Microvascular disease (MVD) describes systemic changes in the small vessels (∼100 υm diameter) that impair tissue oxygenation and perfusion. Emerging evidence has shown that MVD (which is prevalent in diabetics) is clinically relevant as it synergistically acts with peripheral arterial disease to increase the risk of limb loss by 22.7-fold. Poor glycemic control has been linked to clinical microvascular disease (nephropathy and retinopathy) However, the direct impact of poor glycemic control on the microcirculation of the feet is unknown as there are currently no standardized non-invasive methods used clinically to assess and quantify MVD of the lower limbs. Spatial frequency domain imaging (SFDI) is a novel non-invasive optical technology that can detect and quantify microvascular disease of the foot by measuring the amount of hemoglobin(HbT1) in the capillaries of the superficial dermis up to 1-2mm deep and oxygenation (StO2) in the dermal micro-circulation. We hypothesize that poor glycemic control in DM affects pedal microcirculation and the changes can be detected using the SFDI technology. Methods: 307 patients (600 lower extremity limbs) were prospectively enrolled at a single institution, Banner University Medicine, Tucson, AZ from 2016- 2023. Diabetic patients were stratified into three groups based on their HbA1c level: ≤6.7%, 6.8-9.9%, and ≥10%. Mann U Whitney test and Spearman rank correlation were used in testing the association between HbA1C and SFDI-metrics with p<.05 considered as statistical significance. Results: We included 230 lower limbs belonging to diabetic patients. The mean age of the patients was 61.7 years. Clinical neuropathy and retinopathy were found in 79% and 30.7% of patients, respectively. SFDI-derived biomarkers of microcirculation were compared among diabetics categorized by HbA1C levels. We observed a significant reduction in papillary dermal perfusion (HbT1) as the glycemic control (HbA1C) of the patients worsened (p<0.001). Although tissue oxygenation (StO2) was not statistically different across diabetic groups, the St02/HbT1 ratio which represents the ratio of tissue oxygenation to perfusion, increased with elevated HbA1C levels. This indicated that poorly controlled diabetics had less oxygen being extracted from their poorly perfused micro-circulation. Conclusions: This study suggests that poor glycemic control directly affects the microcirculation of the feet in diabetic patients. The SFDI technology is a promising noninvasive tool to evaluate microvascular disease of the feet and potentially may be utilized clinically to stratify diabetic patients at risk for foot ulceration or limb loss based on glycemic control over time. Presentation: Friday, June 16, 2023

Impact of poor glycemic control upon clinical outcomes after radical prostatectomy in localized prostate cancer

To evaluate the clinical impact of preoperative glycemic status upon oncological and functional outcomes after radical prostatectomy in patients with localized prostate cancer, we analyzed the data of 2664 subjects who underwent radical prostatectomy with preoperative measurement of hemoglobin A1c within 6 months before surgery. The possible association between high hemoglobin A1c (≥ 6.5 ng/dL) and oncological/functional outcomes was evaluated. Among all subjects, 449 (16.9%) were categorized as the high hemoglobin A1c group and 2215 (83.1%) as the low hemoglobin A1c group. High hemoglobin A1c was associated with worse pathological outcomes including extra-capsular extension (HR 1.277, 95% CI 1.000–1.630, p = 0.050) and positive surgical margin (HR 1.302, 95% CI 1.012–1.674, p = 0.040) in multi-variate regression tests. Kaplan–Meier analysis showed statistically shorter biochemical recurrence-free survival in the high hemoglobin A1c group (p < 0.001), and subsequent multivariate Cox proportional analyses revealed that high hemoglobin A1c is an independent predictor for shorter BCR-free survival (HR 1.135, 95% CI 1.016–1.267, p = 0.024). Moreover, the high hemoglobin A1c group showed a significantly longer incontinence-free survival than the low hemoglobin A1c group (p = 0.001), and high preoperative hemoglobin A1c was also an independent predictor for longer incontinence-free survival in multivariate Cox analyses (HR 0.929, 95% CI 0.879–0.981, p = 0.008). The high preoperative hemoglobin A1c level was independently associated with worse oncological outcomes and also with inferior recovery of urinary continence after radical prostatectomy.

Risk for developing perianal abscess in type 1 and type 2 diabetes and the impact of poor glycemic control

PurposeThe primary aim of this study was to see whether perianal abscess rate differs between patients with type 1 and type 2 diabetes. A secondary aim was to determine whether poor glycemic control increases the risk for perianal abscess.MethodsData from the Swedish National Diabetes Registry and the Swedish National Patient Registry between January 2008 and June 2015 were matched. The risk for anal abscess was evaluated in univariate and multivariate analyses with type of diabetes, HbA1c level, BMI, and various diabetes complications as independent factors.ResultsPatients with type 1 diabetes had a lower rate of perianal abscess than patients with type 2 diabetes when adjusted for HbA1c, sex, and age (OR 0.65; 95% CI 0.57–0.73). The risk for perianal abscess increased with higher HbA1c. Incidence of perianal abscess was also elevated in diabetes patients with complications related to poor glycemic control such as ketoacidosis and coma (OR 2.63; 95% CI 2.06–3.35), gastroparesis, and polyneuropathy (OR 1.81; 95% CI 1.41–2.32).ConclusionsThe prevalence of perianal abscess was higher among patients with type 2 diabetes than those with type 1, suggesting that metabolic derangement may be more important than autoimmune factors. Poor glycemic control was associated with higher risk for perianal abscess.

The impact of poor glycemic control on lipid profile variables in children with type 1 diabetes mellitus.

BACKGROUND:Type 1 diabetes mellitus (T1DM) and its related comorbidities are considered an important health issue. This study aimed to evaluate the impact of glycemic control on lipid profile variables in children with T1DM.MATERIALS AND METHODS:This study included 274 children (≤19 years of age) with T1DM who had referred to the outpatient clinics of endocrinology in Emam-Hossein Hospital of Isfahan, Iran. Based on American Diabetes Association criteria, patients were divided into two groups including optimal glycemic control (OGC) and poor glycemic control (PGC). Mean lipid level and frequencies of lipid profile abnormalities between the two studied groups were compared.RESULTS:Mean age of the studied population was 13 ± 5.9 years and 133 (48.5%) were boys. A total of 162 (59.1%) and 112 (40.9%) patients had PGC and OGC, respectively. Hypercholesterolemia was the most common dyslipidemia in both groups (33 [29.1%] of OGC and 63 [39.1%] of PGC patients). The frequency of high low-density lipoprotein (LDL) was significantly higher in patients with PGC than those with OCG (P = 0.007). The frequencies of hypercholesterolemia, hypertriglyceridemia, and low levels of high-density lipoprotein were also higher in PGC group, but did not reach the significant threshold.CONCLUSION:It is suggested that glycemic control is in association with lipid profile abnormality in patients with T1DM. High LDL was significantly more frequent in patients with PGC than those with OGC. It is recommended to investigate the role of glycemic control on other cardiometabolic risk factors of T1DM patients. Our findings could be used for planning preventative strategies for reducing T1DM-related cardiovascular disease.

Impact of hemoglobin A1c levels on asymptomatic bacteriuria in type 2 diabetes mellitus

Background: Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. Infections occur more commonly in patients with DM due to the hyperglycemic medium that increases the virulence of pathogen. Aims and Objectives: The present study was aimed to determine the impact of poor glycemic control as a risk factor for symptomatic urinary tract infection (UTI) in diabetic patients with asymptomatic bacteriuria (ASB) during follow-up. Materials and Methods: This was a cross-sectional observational study conducted at Vinayaka Missions Medical College on diabetic patients. Hemoglobin Alc (HbA1c) was quantified spectrophotometrically using HbA1c test kits. All participants were instructed strictly to collect midstream urine sample. Urine samples collected from participants were inoculated on blood agar and MacConkey agar and incubated for overnight at 370°C. If growth occurs, organism was identified by standard microbiological procedures. Symptomatic UTI surveillance was done by instructing participants to contact research personnel if any new symptom/symptoms occurred (follow-up period 3 months) that suggested UTI. Results: A total of 225 participants were included in the study and categorized as diabetic (n = 175) and non-diabetic as control group (n = 50). A total of 107 diabetic patients had

Sedentary behavior as a risk factor for cognitive decline? A focus on the influence of glycemic control in brain health

Cognitive decline leading to dementia represents a global health burden. In the absence of targeted pharmacotherapy, lifestyle approaches remain the best option for slowing the onset of dementia. However, older adults spend very little time doing moderate to vigorous exercise and spend a majority of time in sedentary behavior. Sedentary behavior has been linked to poor glycemic control and increased risk of all-cause mortality. Here, we explore a potential link between sedentary behavior and brain health. We highlight the role of glycemic control in maintaining brain function and suggest that reducing and replacing sedentary behavior with intermittent light-intensity physical activity may protect against cognitive decline by reducing glycemic variability. Given that older adults find it difficult to achieve current exercise recommendations, this may be an additional practical strategy. However, more research is needed to understand the impact of poor glycemic control on brain function and whether practical interventions aimed at reducing and replacing sedentary behavior with intermittent light intensity physical activity can help slow cognitive decline.

Impact of poor glycemic control of type 2 diabetes mellitus on serum prostate-specific antigen concentrations in men.

BackgroundTo evaluate the impact of poor glycemic control of type 2 diabetes mellitus (T2DM) on serum prostate-specific antigen (PSA) concentrations in men.MethodsWe performed a prospective analysis of 215 consecutive patients affected by erectile dysfunction (ED). ED was evaluated using the IIEF-5 questionnaire and the poor glycemic control (PGC) of T2DM was assessed according to the HbA1c criteria (International Diabetes Federation). Patients were divided into PGC group (HbA1c ≥ 7%) and control group (CG) (HbA1c < 6%). Correlations between serum HbA1c levels and various variables were evaluated and multivariate logistic regression analyses were carried out to identify variables for PGC.ResultsWe compared 110 cases to 105 controls men ranging from 44 to 81 years of age, lower PSA concentrations were observed in men with PGC (PGC mean PSA: 0.9 ng/dl, CG mean PSA: 2.1 ng/dl, p < 0.001). Also mean prostate volume was 60% was smaller among men with PGC compared with men with CG (PGC mean prostate volume: 26 ml, CG prostate volume: 43 ml, p < 0.001). A strong negative correlation was found between serum HbA1c levels and serum PSA (p < 0.001 and r = −0.665) concentrations in men with PGC. We also found at the multivariate logistic regression model that PSA, prostate volume and peak systolic velocity were independent predictors of PGC.ConclusionOur results suggest that there is significant impact of PGC on serum PSA levels in T2DM. Poor glycemic control of type 2 diabetes was associated with lower serum PSA levels and smaller prostate volumes.

PDB71 - Investigating the Short-Term Impact of Poor Glycemic Control on the daily lives of People with type 2 Diabetes

Investigating the short-term impact of poor glycemic control on the daily lives of people with type 2 diabetes

Identification of De Novo Synthesized and Relatively Older Proteins

OBJECTIVEThe accumulation of old and damaged proteins likely contributes to complications of diabetes, but currently no methodology is available to measure the relative age of a specific protein alongside assessment of posttranslational modifications (PTM). To accomplish our goal of studying the impact of insulin deficiency and hyperglycemia in type 1 diabetes upon accumulation of old damaged isoforms of plasma apolipoprotein A-1 (ApoA-1), we sought to develop a novel methodology, which is reported here and can also be applied to other specific proteins.RESEARCH DESIGN AND METHODSTo label newly synthesized proteins, [ring-13C6]phenylalanine was intravenously infused for 8 h in type 1 diabetic participants (n = 7) during both insulin treatment and 8 h of insulin deprivation and in nondiabetic participants (n = 7). ApoA-1 isoforms were purified by two-dimensional gel electrophoresis (2DGE) and assessment of protein identity, PTM, and [ring-13C6]phenylalanine isotopic enrichment (IE) was performed by tandem mass spectrometry.RESULTSFive isoforms of plasma ApoA-1 were identified by 2DGE including ApoA-1 precursor (pro-ApoA-1) that contained the relatively highest IE, whereas the older forms contained higher degrees of damage (carbonylation, deamidation) and far less IE. In type 1 diabetes, the relative ratio of IE of [ring-13C6]phenylalanine in an older isoform versus pro-ApoA-1 was higher during insulin deprivation, indicating that de novo synthesized pro-ApoA-1 more rapidly accumulated damage, converting to mature ApoA-1.CONCLUSIONSWe developed a mass spectrometry–based methodology to identify the relative age of protein isoforms. The results demonstrated accelerated oxidative damage to plasma ApoA-1, thus offering a potential mechanism underlying the impact of poor glycemic control in type 1 diabetic patients that affects a patient's risk for vascular disease.

Glycemic control and cardiovascular disease in chronic kidney disease

Diabetes increases cardiovascular (CV) risk to a similar extent as myocardial infarction. Epidemiologic data support the same concept for the presence of Stage 3 (ie, glomerular filtration rate of < 60 mL/min) or higher nephropathy without diabetes. The most common cause of end-stage kidney disease requiring dialysis is diabetes. Hence, CV risk is highest among those with kidney disease and diabetes. Glycemic control in the context of CV risk reduction among patients with kidney disease has not been the focus of any specific trial; however, secondary analyses of trials, primarily in type 1 diabetes, have looked at this issue. Nevertheless, the outcome data are sparse. What can be said, however, is that failure to achieve reasonable glycemic control (ie, glycated hemoglobin < 7.5%) is associated with a higher risk of CV events and hospitalizations for CV events and infections among those with advanced kidney disease. The impact of poor glycemic control on kidney disease progression has not been well studied and should be the focus of future studies.

Hypothalamic-Pituitary-Adrenal Axis Dysregulation and Memory Impairments in Type 2 Diabetes

There is evidence of both hypothalamic-pituitary-adrenocortical (HPA) axis and cognitive dysfunction in type 2 diabetes mellitus (T2DM). However, the exact nature and the associations between these abnormalities remain unclear. The aim of the study was to characterize the nature of the HPA dysregulation in T2DM and ascertain whether impaired cognition in T2DM could be attributed to these abnormalities. A cross-sectional study was performed, contrasting matched groups on HPA axis function and cognition by using the combined dexamethasone (DEX)/CRH test and a neuropsychological battery assessing declarative and working memory, attention, and executive function. The study was conducted in a research clinic in an academic medical center. Participants were volunteers functioning in the cognitively normal range. We studied 30 middle-aged individuals with T2DM, on average 7.5 yr since diabetes diagnosis, and 30 age-, gender-, and education-matched controls. Basal cortisol levels, cortisol levels during the DEX/CRH test, and performance on neuropsychological tests were measured. Individuals with T2DM had elevated basal plasma cortisol levels, higher levels after DEX suppression, and a larger response to CRH (all P <or= 0.005). Among individuals with T2DM, cortisol levels during the DEX/CRH test were positively associated with glycosylated hemoglobin (P = 0.05), independent of age, body mass index, hypertension, and dyslipidemia. Diabetic subjects showed cognitive impairments restricted to declarative memory. Across all subjects, declarative memory was inversely associated with cortisol levels; however, these associations were subsumed by glycemic control (glycosylated hemoglobin). HPA hyperactivity and declarative memory deficits are present in T2DM. Both alterations may reflect the negative impact of poor glycemic control on the hippocampal formation.

Glycemic control and radiographic manifestations of pulmonary tuberculosis in patients with type 2 diabetes mellitus

Background: Diabetes mellitus (DM) is a risk factor for tuberculosis (TB) and may modify its presenting features. Atypical radiologic images of pulmonary TB are common in DM. Many studies have compared the radiological manifestations of TB between patients with and without DM. Aim of the Study: To study the impact of poor glycemic control on radiographic manifestations of the newly diagnosed smear-positive pulmonary TB patients with type 2 DM. Materials and Methods: In a tertiary care hospital, 70 patients newly diagnosed with smear-positive pulmonary TB and with coexisting type 2 DM were enrolled. Glycemic control was assessed by glycosylated hemoglobin (HbA1 C ). A pretreatment chest radiograph was read independently by two qualified pulmonologists blinded to patients' diabetic status. Films with any discordant reading were read by a third reader. Radiological lesions on chest radiograph were classified into minimal, moderately advanced and far advanced as per American Thoracic Society criteria. Results: Of 70 patients, 47 (67.1%) had their HbA1c level ΃7%. Patients with poor glycemic control (HbA1c ΃7%) were more likely to have lower lung field involvement (29.8% vs. 13.04%; P < 0.01), far advanced lesions (40% vs. 4%; P < 0.001) and cavitary disease on chest radiograph (76.6% vs. 43.4% P < 0.05). Conclusion: Poor glycemic control significantly influences radiographic manifestations of pulmonary TB in patients with DM. Uncontrolled diabetics seem to have multiple and large cavities. Also isolated lower lung field involvement is more common in uncontrolled diabetics than in optimal control patients. High index of suspicion is, therefore, required in uncontrolled diabetics when radiological patterns are atypical.