Effect Of Poor Glycemic Control Research Articles

Effect of poor glycemic control on the prevalence and determinants of anemia and chronic kidney disease among type 2 diabetes mellitus patients in Jordan: An observational cross-sectional study.

Anemia and chronic kidney disease (CKD) are common findings in diabetic patients. Lack of glycemic control is associated with increased risk of diabetic complications. This study aimed to determine the effect of poor glycemic control on the prevalence and determinants of anemia and CKD among type 2 diabetes mellitus (T2DM) patients in Jordan. A cross-sectional study design was used in this research. T2DM patients with controlled diabetes (HbA1c ≤7.0%, n = 120) and age-, gender- and body mass index-matched uncontrolled diabetic patients (HbA1c >7.0%, n = 120) were recruited. Blood sample for HbA1c and serum insulin measurement were obtained. Complete blood count and kidney function test results were obtained from the patient's medical records. Anemia was determined according to World Health Organization criteria. A binomial logistic regression was performed to ascertain the effects of age, gender, CKD and glycemic control on the likelihood that participants have anemia. The prevalence of anemia was significantly higher in the uncontrolled T2DM compared to controlled T2DM patients (40% vs 27.5%, OR: 2.14, 95% CI: 1.23, 3.71, P = 0.006). Female patients with uncontrolled T2DM had significantly greater prevalence of anemia compared to male patients with uncontrolled T2DM. The binomial logistic regression analysis showed that age, female gender, and CKD were positively associated with anemia in the multivariate model, while in the univariate model, lack of glycemic control increases the odds of anemia by 1.74 (95% CI: 1.01, 2.99, P = 0.046). Anemia is commonly present among T2DM patients in Jordan and is associated with poor glycemic control especially in females. These results emphasize the necessity of including anemia screening in standard diabetes care to enable early detection and treatment of anemia and to enhance the overall care of diabetic patients.

The effect of poor glycemic control on cognitive function in children and adolescents with type 1 diabetes mellitus: A single-center cross-sectional study (2019-2020).

To investigate the effect of chronic hyperglycemia, hypoglycemia, and diabetic ketoacidosis (DKA) on the cognitive function of children and adolescents with type 1 diabetes mellitus (T1DM), and explore whether early disease onset correlated with cognitive impairment. Children and adolescents with T1DM who attended the Pediatric Diabetes Clinic between January 2019 and 2020, aged between 5-14 years, with a mean of 3 glycated hemoglobin (HbA1c) readings ≥7% (53 mmol/mol) during the study period reflecting a hyperglycemic status and who agreed to participate were interviewed about their history of hypoglycemia and DKA. Participants were personally interviewed by a clinical psychologist to assess their cognitive function using a validated Arabic version of the Stanford-Binet test. Higher mean HbA1c levels were associated with cognitive dysfunction in three verbal domains: fluid reasoning, quantitative reasoning, and working memory. Frequent hypoglycemia negatively affected verbal knowledge. In contrast, significant hypoglycemia affected both verbal and nonverbal domains of cognition, specifically verbal and nonverbal fluid reasoning, knowledge, and working memory. Children with recurrent DKA performed below average in nonverbal fluid reasoning tasks. Additionally, moderate or severe DKA, regardless of its frequency, affected children's overall intelligence quotient. Regardless of disease onset, exposure to glycemic variability subjects children and adolescents to subtle and measurable cognitive dysfunction resulting in significant morbidity.

Investigating glycemic control in patients undergoing lower extremity bypass within an enhanced recovery pathway at a single institution

BackgroundEnhanced recovery pathways (ERPs) aim to lower perioperative stress to facilitate recovery. Limited fasting combined with carbohydrate loading is a common ERP element. The effect of limited fasting has not been elucidated in patients with diabetes. Given the known deleterious effects of poor glycemic control in the perioperative period, such as increased rates of surgical site infection, the associations of preoperative limited fasting with perioperative glycemic control and early outcomes after lower extremity bypass (LEB) were investigated. MethodsA single institutional retrospective review of patients who underwent infrainguinal LEB from 2016 to 2022 was performed. The ERP was initiated in May 2018. Patients were stratified by diabetes diagnosis and preoperative hemoglobin A1C (HbA1C) levels. Perioperative glycemic control was compared between the limited fasting and traditional fasting patients (nil per os at midnight). Limited fasting was defined as a clear liquid diet until 2 hours before surgery with recommended carbohydrate loading consisting of 400 cc of a clear sports drink (approximately 30 g of carbohydrates). All limited fasting patients were within the ERP. Early perioperative hyperglycemia (EPH) was defined as blood glucose of >180 mg/dL within the first 24 hours of surgery. Perioperative outcomes such as surgical site infection, readmission, reinterventions, and complications were also compared. ResultsA total of 393 patients were included (limited fasting patients N = 135; traditional fasting patients N = 258). A trend toward EPH was seen in all limited fasting groups. Evaluating limited fasting within diabetic patients revealed that 74.5% of limited fasting-diabetic patients had EPH compared with 49.6% of traditional fasting-diabetic patients (P = .001). When stratified by the HbA1C level, a significantly higher rate of EPH was seen in the HbA1c >8.0% groups, with 90.5% in the limited fasting patients compared with 67.9% in traditional fasting patients (P = .05). Limited fasting-diabetic patients experience a longer postoperative length of stay at 5.0 days (interquartile range: 3, 9) vs 4.0 days (2, 6) in nondiabetic patients (P = .016). ConclusionsERP limited fasting was associated with early perioperative hyperglycemia after LEB, particularly in patients with HbA1C >8.0%. Due to the high prevalence of diabetic patients undergoing LEB under ERP, the role of limited fasting and common glycemic elements of ERP may need to be re-evaluated in this subpopulation.

Hemoglobin A1c Levels Impact Patency and Adverse Limb Events in Diabetics After Revascularization

The effect of poor glycemic control in the perioperative and postoperative period has been reported to be associated with early and late major adverse limb events (MALE); however, these studies were mostly from databases, lacked granular data and long-term outcomes. We examined the long term effects of high hemoglobin A1c level on patency, MALE, limb salvage (LS) and survival after lower extremity revascularization in diabetic patients.

Evaluation of the Impact of Glycemic Control on Mean Platelet Volume and Platelet Activation in Children with Type 1 Diabetes.

The studies evaluating cases with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in the adult population reported hyperreactive platelets and increased activation of prothrombotic factors, resulting in an increased risk of thrombosis. The aim of this study was to evaluate the effects of poor glycemic control and the duration of diabetes on platelet parameters in pediatric population. The study included 366 children, out of which 144 (39.3%) were included in the T1DM group and 222 (60.6%) in the healthy control group. The platelet count, mean platelet volume (MPV), platelet distribution width and plateletcrit values were recorded. The children with T1DM were divided into three groups as per their glycated hemoglobin (HbA1c) levels, good (<7.5%), moderate (7.5-9%) and poor metabolic control (>9%). No significant difference in the MPV level between the T1DM (7.41 ± 1.49 fl) and control (7.15 ± 1.23 fl) groups was observed. However, the MPV levels were significantly higher in the poor glycemic control group than in the healthy control group (p = 0.026). Furthermore, as the duration of diabetes and HbA1c levels increased, the MPV levels also increased (p < 0.001, p = 0.441). This study suggested as the duration of diabetes and HbA1c levels increased, the MPV levels also increases. Evaluation of hematological parameters can be a cheap and useful method in the evaluation of diabetes regulation in patients with diabetes.

Effects of poor glycemic control on mortality and severity of COVID-19 disease.

Most patients with a severe COVID-19 infection have underlying diseases such as hypertension, cardiovascular disorders, and diabetes, and the mortality rate in these patients is higher than in other patients. Reasonable glycemic control is a practical approach to prevent the progression of COVID-19 in patients with diabetes. In this study, we aimed at demonstrating that glycemic control status can be used as a biomarker in predicting the severity of the disease in the early period in diabetic patients with COVID-19. Our retrospective study consisted of 122 patients who referred to Sinop Ayancik State Hospital between April 1, 2020, and April 1, 2021. 40 diabetic patients with poor glycemic control (HbA1C above 7), 40 diabetic patients with reasonable glycemic control (HgA1c below 7), and 42 patients without diabetes were included in the study. The patients' data included in the study were obtained by scanning the retrospective files. These patients' demographic characteristics, clinical features, age, gender, length of stay, hemogram, biochemical, hormonal parameters, HgA1c levels, and atherogenic indexes were calculated and recorded. Study groups were compared in terms of disease severity and mortality. A statistically significant difference was found between mild/severe conditions (p-value < 0.001). 72.5% of those with poor glycemic control, 57.5% of those with reasonable glycemic control, and 26.2% without diabetes had severe diseases. Also, a statistically significant difference was found between the distributions of death rate (p = 0.008). 17.5% of those with poor glycemic control, 5% of those with reasonable glycemic control, and 0% of patients without diabetes died. Our results showed that poor glycemic control was an effective indicator of disease severity and mortality in patients with COVID-19 and could predict disease progression and mortality.

Preoperative Hemoglobin A1c >7.5 Is Associated With Increased Bundled Payment Costs in Total Hip and Knee Arthroplasties.

Studies have shown that patients with diabetes mellitus are at an increased risk for complications and higher episode-of-care costs after total hip (THA) and total knee arthroplasties (TKA), but the effect of poor glycemic control on episode-of-care costs has yet to be addressed in the literature. The purpose of this study was to determine whether patients with a higher preoperative hemoglobin A1c have increased episode-of-care costs in diabetic patients undergoing THA and TKA. We reviewed a consecutive series of 9,511 primary THA and TKA patients between 2015 and 2018. We recorded demographics, medical comorbidities, and hemoglobin A1c for patients with diabetes mellitus. We compared complications, readmissions, and 90-day episode-of-care costs from Medicare claims data across A1c levels. A multivariate logistic regression analysis was done to assess the independent effect of A1c on episode-of-care costs. Diabetic patients (n = 1,042) had higher episode-of-care costs ($20,577 vs $19,414, P < 0.001) than patients without diabetes. Higher stratified A1c levels were associated with increasing mean episode-of-care costs (6.5% to 6.9% = $18,912; 7.0% to 7.49% = $19,832; 7.5% to 7.9% = $20,827; >8% = $21,169). In multivariate analysis, patients with hemoglobin A1c >7.5% had higher episode-of-care costs ($2,331, 95% confidence interval, $511-$4,151, P = 0.012). Those with a hemoglobin A1c >7.5% had increased rates of complications (7% vs 3%, P = 0.049) and readmissions (11% vs 5%, P = 0.020). Hemoglobin A1c levels above 7.5% are associated with increased episode-of-care costs, complications, and readmissions after THA and TKA. Optimizing glycemic control before surgery may improve quality of care and lead to success in Medicare bundled payment models.

Effect of poor glycemic control in cognitive performance in the elderly with type 2 diabetes mellitus: The Mexican Health and Aging Study

BackgroundCognitive impairment is twice more frequent in elderly with type 2 diabetes mellitus (DM). This study was conducted to determine the association between glycemic control and cognitive performance among community-dwelling elderly persons in Mexico.MethodsCross-sectional study conducted in individuals aged 60 years or elderly participating in the 2012 Mexican Health and Aging Study. Type 2 DM participants were classified in 3 groups according to their glycated hemoglobin levels (HbA1c): < 7% (intensive control), 7–7.9% (standard control) or ≥ 8% (poor control), and cognitive performance: low (CCCE ≤44 points), intermediate (44.1–59.52 points), or high (≥59.53 points). Multinomial logistic regression models were constructed to determine this association.ResultsTwo hundred sixteen community-dwelling adults aged 60 and older with type 2 diabetes were selected. Subjects in the low cognitive performance group were older (69.7 ± 6.6 vs 65.86 ± 5.18 years, p < .001) and had a lower educational level (2.5 ± 2.6 vs 7.44 ± 4.15 years, p < .000) when compared to the high cognitive performance participants. HbA1c ≥ 8% was associated with having low (Odds Ratio (OR) 3.17, 95% CI 1.17–8.60, p = .024), and intermediate (OR 3.23, 95% CI 1.27–8.20, p = .014) cognitive performance; this trend was not found for HbA1c 7.0–7.9% group.The multinomial regression analysis showed that the presence of HbA1c ≥ 8% (poor glycemic control) was associated with low (OR 3.17, 95% CI = 1.17–8.60, p = .024), and intermediate (OR 3.23, 95% CI = 1.27–8.20, p = .014) cognitive performance. After adjusting for confounding variables.ConclusionsGlycemic control with a HbA1c ≥ 8% was associated with worse cognitive performance.

High hemoglobin A1c associated with increased adverse limb events in peripheral arterial disease patients undergoing revascularization

ObjectiveDiabetes and peripheral arterial disease (PAD) are independently associated with increased risk of amputation. However, the effect of poor glycemic control on adverse limb events has not been studied. We examined the effects of poor glycemic control (high hemoglobin A1c level) on the risk of amputation and modified major adverse limb events (mMALEs) after lower extremity revascularization. MethodsPatients undergoing PAD revascularization who had hemoglobin A1c (HbA1c) levels available within 6 months were identified in the Veterans Affairs database of 2003 to 2014 (N = 26,799). The diagnosis of preoperative diabetes mellitus (PreopDM) was defined using diabetes diagnosis codes and evidence of treatment. Amputation and mMALE risk was compared for HbA1c levels using Kaplan-Meier analysis. Cox proportional hazards models were created to assess the effect of high HbA1c levels on amputation and mMALE (adjusted for age, gender, race, socioeconomic status, comorbidities, cholesterol levels, creatinine concentration, suprainguinal or infrainguinal procedure, open or endovascular procedure, severity of PAD, year of cohort entry, and medications) for all patients and stratified by PreopDM. ResultsHigh HbA1c levels were present in 33.2% of the cohort, whereas 59.9% had PreopDM. Amputations occurred in 4359 (16.3%) patients, and 10,580 (39.5%) had mMALE. Kaplan-Meier curves showed the worst outcomes in patient with PreopDM and high HbA1c levels. In the Cox model, incremental HbA1c levels of 6.1% to 7.0%, 7.1% to 8.0%, and >8% were associated with 26% (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.15-1.39), 53% (HR, 1.53; 95% CI, 1.37-1.7), and 105% (HR, 2.05; 95% CI, 1.87-2.26) higher risk of amputation, respectively. Similarly, the risk of mMALE also increased by 5% (HR, 1.05; 95% CI, 0.99-1.11), 21% (HR, 1.21; 95% CI, 1.13-1.29), and 33% (HR, 1.33, 95% CI, 1.25-1.42) with worsening HbA1c levels of 6.1% to 7.0%, 7.1% to 8.0%, and >8%, respectively (vs HbA1c ≤6.0%). In stratified analysis by established PreopDM, the relative risk of amputation or mMALE was much higher with poor glycemic control (HbA1c >7.0%) in patients without PreopDM. ConclusionsPAD patients with worse perioperative glycemic control have a significantly higher risk of amputation and mMALE. Incremental increases in HbA1c levels are associated with higher hazards of adverse limb outcomes independent of PreopDM status. Poor glycemic control (HbA1c >7.0%) in patients without a PreopDM diagnosis carries twice the relative risk of amputation and mMALE than in those with good glycemic control. These results suggest that screening of diabetic status and better management of glycemic control could be a target for improvement of perioperative and long-term outcomes in PAD patients.

Effect of Vildagliptin, Compared to Sitagliptin, on the Onset of Hyperglycemia-Induced Metabolic Memory in Human Umbilical Vein Endothelial Cells

Background: Metabolic memory, the long-term effect of poor glycemic control in the initial stages of diabetes, leads to vascular complications that negatively affect patients’ outcome. As oxidative stress plays a major role in metabolic memory onset, the use of drugs with antioxidant properties may be clinically beneficial. Objectives: To test the effects of two dipeptidyl peptidase-4 inhibitors, vildagliptin and sitagliptin, on hyperglycemia-induced oxidative stress and apoptosis in Human Umbilical Vein Endothelial Cells (HUVECs). Methods: HUVECs were treated with 5 nM vildagliptin or sitagliptin for 1 h, after 21 days of culture under conditions of continuous normal or high glucose (NG and HG, respectively), Oscillating Glucose (OG) or HG/OG memory (HM and OM, respectively). The effects of the two drugs on the following markers of oxidative stress were tested by different techniques: Reactive Oxygen Species (ROS), 8-hydroxy-deoxy-guanosine, 3-nitrotyrosine, thioredoxin-interacting protein (TXNIP) mRNA and PKC-β protein. Moreover, the levels of BCL-2 (anti-apoptotic) and BAX (pro-apoptotic) transcripts and of caspase-3 protein were assayed. Results: In HUVECs, vildagliptin was able to significantly counteract the oxidative stress triggered by OG, HG and memory conditions, as measured by the levels of ROS, DNA and protein damage markers, TXNIP and PKC-β. Also, a significant increase of BCL-2 and decrease of BAX mRNA levels was observed upon OG and HG. Sitagliptin exerted a less evident effect. No significant effect on caspase-3 levels was detected by either drug. Conclusions: Our findings point toward antioxidant and antiapoptotic properties of vildagliptin in HUVECs exposed to HG, OG and metabolic memory conditions, whereas the effects of sitagliptin were less prominent. If these results on the vascular protective effects of vildagliptin will be confirmed, its use may be implemented in the setting of diabetes to prevent the onset of metabolic memory.

High Hemoglobin A1c Associated with Increased Adverse Limb Events in Peripheral Arterial Disease Patients Undergoing Revascularization

Diabetes mellitus (DM) and peripheral arterial disease (PAD) are independently associated with increased risk of amputation. However, the effect of poor glycemic control on adverse limb events has yet to be fully defined. In this study, we examined the effects of poor glycemic control as defined by high hemoglobin A1c (HbA1c ≥ 7.0%) on the risk of amputation and need for subsequent revascularization after lower extremity revascularization. Patients undergoing PAD revascularization who had HbA1c levels available within 6 months before or after revascularization were identified in the VA database from 2003 to 2014 (N = 26,799). The diagnosis of preoperative DM (pre-op DM) was defined using a primary clinic DM diagnosis code, 2 outpatient diagnosis codes or treatment for DM before the revascularization. Major amputation and major adverse limb event (MALE, amputation or need for subsequent revascularization) risk was measured at 30 days, 1 year, and 5 years after revascularization. Cox proportional hazards models were created to assess the effect of high HbA1c on amputation/MALE (adjusted for covariates, including age, sex, race, socioeconomic status, comorbidities, cholesterol levels, creatinine, supra/infrainguinal procedure, open/endovascular procedure and medications) for all patients and stratified on pre-op DM. High HbA1c levels were present in 33.2% of the cohort while 26.5% had pre-op DM. Major amputations occurred in 4359 (16.3%) patients, and 10,580 (39.5%) had MALE in follow-up. Bivariate comparisons showed increased risk of amputation at 30 days, 1 year, and 5 years for patients with high HbA1c (5.8% vs 3.9%, 14.9% vs 9.0% and 21.1% vs 12.2%, respectively; P < .0001). MALE was also similarly higher in patients with high HbA1c at each time point (11.4% vs 8.8%, 32.6% vs 25.6% and 44.4% vs 34.8%, respectively; P < .0001). Kaplan-Meier curves showed worst outcomes in patient with pre-op DM and high HbA1c. In the Cox model, High HbA1c was associated with a 77% higher amputation risk and 33% higher MALE risk compared with patients with normal glycemic control while a preoperative diagnosis of DM was associated with a 53% and 22% increase in amputation and MALE risk as shown in the Table. In stratified analysis the relative risk of amputation/MALE was much higher with poor glycemic control in patients without a preoperative diagnosis of diabetes as compared with those with it (Table). Patients with PAD who have poor perioperative glycemic control (HbA1c ≥7.0%) have a significantly higher risk of amputation and MALE than patients with good glycemic control. Poor glycemic control in patients without a preoperative diagnosis of DM carries twice the relative risk of amputation and MALE than those with good glycemic control. These results suggest that screening of diabetic status and management of glycemic control could be a target for improvement of perioperative and long-term outcomes in patients with PAD.TableCox proportional hazards regression model: hazard ratios (HR) for occurrence of major amputation or major adverse limb events (MALE) with poor glycemic control (HbA1c ≥7%) in peripheral arterial disease (PAD) patients undergoing revascularizationFull modelAmputation, HR (95% confidence interval)MALE, HR (95% confidence interval)Poor glycemic control1.77 (1.65, 1.90)1.33 (1.27, 1.39)Pre-op DM1.53 (1.42, 1.65)1.22 (1.16, 1.28)Stratified by preoperative diagnosis of diabetes mellitus (PreopDM) No diagnosis of pre-op DMPoor glycemic control2.11 (1.92, 2.31)1.43 (1.35, 1.51) Pre-op DM diagnosis presentPoor glycemic control1.34 (1.20, 1.50)1.18 (1.09, 1.28)DM, Diabetes mellitus. Open table in a new tab

Effect of poor glycemic control on arterial stiffness in pregnancy

Effect of poor glycemic control on arterial stiffness in pregnancy

Relationship of Cardiac Structure and Function to Cardiorespiratory Fitness and Lean Body Mass in Adolescents and Young Adults with Type 2 Diabetes

To investigate the relationships of cardiac structure and function with body composition and cardiorespiratory fitness (CRF) among adolescents with type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth study. Cross-sectional evaluation of 233 participants (median age 18.3 [min-max 12.4-24.2] years, 63% females, median hemoglobin A1c 6.8%) who had echocardiography measurements of left ventricular (LV) mass, ejection fraction, left atrial dimensions, LV diastolic function (early transmitral flow velocity to early mitral annular velocity ratio from tissue Doppler imaging), and right ventricular function (tricuspid annular plane systolic excursion [TAPSE]) and body composition (dual-energy x-ray absorptiometry) and CRF (cycle ergometry determination of physical work capacity at heart rate of 170 beats per minute). LV mass correlated positively with CRF (r = 0.5, P < .0001), lean body mass (LBM) (r = 0.7, P < .0001), and fat mass (FM) (r = 0.2, P = .00047); LV ejection fraction did not. Early transmitral flow velocity to early mitral annular velocity was positively related to FM (r = 0.14, P = .03) and % body fat (r = 0.18, P = .007), and left atrial internal diameter correlated with FM (r = 0.4, P < .0001), LBM (r = 0.3, P < .001), and CRF (r = 0.2, P = .0033). TAPSE weakly correlated with CRF (r = 0.2, P = .0014) and LBM (r = 0.13, P < .05) but not with FM. In multivariable regression analyses, LBM (β = 2.13, P < .0001) and CRF (β = 0.023, P = .008) were related to LV mass independent of race, sex, age, hemoglobin A1c, hypertension, smoking, and diabetes medications. CRF (β = 0.0002, P = .0187) and hemoglobin A1c (β = -0.022, P = .0142) were associated with TAPSE. In youth with type 2 diabetes, LV size is related to physical fitness. LV ejection fraction is within normal limits. LV diastolic function is inversely related to FM. Greater fitness may counteract adverse effects of poor glycemic control on right ventricular function. ClinicalTrials.gov:NCT00081328.

Epigenetic regulation of glucose-stimulated osteopontin (OPN) expression in diabetic kidney

Diabetes nephropathy (DN) is the leading cause of end stage renal disease and it affects up to 40% of diabetic patients. In addition to hyperglycemia, genetic factors are thought to contribute to the development of DN, but few if any genetic factors have been convincingly linked to DN. Other possible mechanisms may involve epigenetic regulation of glucose-stimulated gene activity which was suggested to explain long-term effects of poor glycemic control on risk of diabetic complications, often referred to as metabolic memory. Osteopontin (OPN) is one of the genes upregulated in kidneys from diabetic mouse models as well as humans with DN, and suggested to play an important role in the pathogenesis of DN. In this study, we demonstrated that OPN gene expression is upregulated in the kidneys of a hyperglycemia diabetes mouse model SUR1-E1506K, and glucose-stimulated OPN gene expression is strongly associated with increases in activating histone marks H3K9ac, H3K4me1 and H3K4me3 and decrease in inactivating mark H3K27me3 in the promoter region of OPN gene. These findings were replicated in human mesangial cells treated with high glucose. Further proof for the involvement of histone acetylation and methylation in glucose-induced changes in OPN gene expression was obtained by manipulating histone modifications thereby OPN gene expression by histone deacetylase (HDAC) inhibitor trichostatin A and histone methyltransferase (HMT) inhibitor MM-102. We conclude that glucose is a potent inducer of histone acetylation and methylation, which in turn leads to upregulation of OPN gene expression. Treatment targeting histone marks may therefore represent an alternative method to protect kidneys from deleterious effects of glucose.

Impairment of long-term potentiation in the hippocampus of alcohol-treated OLETF rats

Type 2 diabetes and chronic heavy alcohol consumption each have been known to be associated with the impairment of hippocampus-dependent cognitive functions. Although both conditions often coexist clinically and there is accumulated evidence of a relationship between the two, the combined effect on hippocampal long-term potentiation (LTP) has not yet been investigated. We compared the effect of type 2 diabetes itself with that of type 2 diabetes with chronic heavy alcohol consumption on the hippocampal LTP using Otsuka Long-Evans Tokushima Fatty (OLETF) rat model, which resembles the characteristics of human type 2 diabetes. Ten of 16-week-old male OLETF rats were randomized into two treatment groups according to weight: the OLETF–Alcohol (O–A, n = 5) and the OLETF–Control (O–C, n = 5). The rats in the O–A group were fed Lieber-DeCarli Regular EtOH over a 10-week period and the amount of alcohol consumption was 8.42 ± 2.52 g/kg/day. To ensure the effect of poor glycemic control on LTP, intraperitoneal glucose tolerance test was performed after a 10-week treatment. The hippocampal LTP was measured by extracellular field excitatory post-synaptic potentials at Shaffer collateral (SC) synapses in the CA1 region. Although the O–A group showed significantly lower fasting and postprandial glucose ( P < 0.01 and P = 0.02, respectively), the hippocampal LTP was more significantly attenuated in the O–A group than the O–C group ( P = 0.032). The results of this study suggested that chronic heavy alcohol consumption could potentiate the impairment of hippocampal LTP in individuals with impaired glucose tolerance or early type 2 diabetes, even though it did not aggravate, but did improve glycemic control. Clinical attention to chronic heavy drinking will be required in preventing cognitive impairment in individuals with type 2 diabetes.

Vitamin B6: Beyond Adequacy

There is good agreement concerning average requirements and reference intakes for vitamin B6but less agreement over safe upper levels from supplements. High-dose supplements cause sensory nerve damage. Supplements of vitamin B6have been advocated for treatment of the premenstrual syndrome, with little evidence of efficacy. There are plausible mechanisms for an antidepressant action and protection against steroid hormone—dependent cancers but no evidence from clinical trials. Pyridoxamine reduces the glycation of proteins and so could be beneficial in preventing the adverse effects of poor glycemic control in diabetes. There are plausible mechanisms for an antihypertensive action but only suggestive evidence from small intervention trials. There is no evidence that supplements of vitamin B6have any beneficial effect in hyperhomocysteinemia. There is neither a plausible mechanism nor any evidence from controlled trials for any effect of supplements of vitamin B6in preventing a decline in cognitive function with aging, amelioration of dementia or autism, or improvement of the carpal tunnel syndrome.

Preaxial hallucal polydactyly as a marker for diabetic embryopathy

Diabetes is the most common endocrinologic complication during pregnancy, and poor control can lead to a variety of congenital anomalies in the fetus. However, it is often difficult to differentiate between diabetes-related anomalies and an underlying genetic syndrome. In the 1990s it was proposed that preaxial hallucal polydactyly, particularly when proximally placed, was a distinguishing feature of diabetic embryopathy. We summarize the clinical findings in 18 patients (five previously reported in abstract form) with diabetic embryopathy and preaxial hallucal polydactyly to determine which features are most suggestive of diabetic embryopathy. All 18 patients had preaxial hallucal polydactyly (seven bilateral, 11 unilateral), of which 15 patients had proximal implantation of the extra hallux. Further skeletal findings included the following: segmentation anomalies of the spine, equinovarus deformity of the feet, tibial hemimelia, hip dysplasia, and femoral hypoplasia. Upper limb malformations were rare. Eleven of the 18 mothers had prepregnancy insulin-dependent diabetes, while one mother had prepregnancy type 2 diabetes that required insulin therapy in the 3(rd) trimester. Five mothers had gestational diabetes that required insulin and one mother had gestational diabetes that was controlled by diet. The majority of mothers had poorly controlled diabetes during the pregnancy. Proximally placed preaxial hallucal polydactyly, particularly when coupled with segmentation anomalies of the spine and tibial hemimelia, is highly suggestive of diabetic embryopathy. Varying degrees of diabetes in the mothers point to a possible genetic predisposition interacting with the teratogenic effects of poor glycemic control leading to specific limb anomalies.

Diabetic osteopahty and vitamin K

Diabetes mellitus is considered as a risk factor for fractures, and there are some reports showing that metabolic effects of poor glycemic control resulted in lower bone turnover. Previous studies have revealed that this reduction of bone turnover increases bone fragility, independently of bone mineral density, so that the mechanisms of diabetic osteopahty seem to be more closely related to bone quality than bone quantity. The mechanisms of the preventive effect on fractures by vitamin K treatment should be related to amelioration of bone quality via increasing amounts of carboxylated osteocalcin. Therefore, administration of vitamin K(2) (menatetrenone) to the patients with diabetic osteopathy will be beneficial in order to improve the impaired bone quality and to reduce fracture risk.

Bone Loss and Bone Turnover in Diabetes

There have been conflicting reports about the effect of diabetes on bone density. In 1978, we studied 109 patients, 46 with type I and 63 with type II diabetes; approximately 12 years later we restudied 35 of the 66 surviving patients. In the original study, radial bone density did not differ significantly between patients with either type of diabetes but was significantly lower than in nondiabetic control subjects. In eight osteopenic patients, bone formation rate and other histological indexes of osteoblast recruitment and function were markedly depressed compared with those in nondiabetic control subjects. In patients remeasured approximately 2.5 years (41 patients) and approximately 12.5 years (35 patients) after baseline, bone loss had continued at the expected rate in patients with type I diabetes, with maintenance of the same deficit, but was slower than expected in patients with type II diabetes, such that the initial deficit had been completely corrected. In six of the eight patients who had undergone bone biopsy, one with type I and five with type II diabetes, the mean bone mineral density z-score of the spine and femoral neck approximately 12 years later was > 0 and in one subject was significantly higher than normal at both sites. Based on these data and on previous studies, we propose that in patients with diabetes, low bone formation retards bone accumulation during growth, metabolic effects of poor glycemic control lead to increased bone resorption and bone loss in young adults, and low bone turnover retards age-related bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)