And HbA1c Research Articles

Protective effects of Artemisia herba-alba in diabetic peripheral artery disease mediated via inhibition of advanced glycation end products

The rationale for undertaking this study is lethality of diabetes mellitus as predicted by 6.7 million deaths in 2021 and immense pharmacological potential of Artemisa herba-alba. The current research examined how Artemisia herba-alba extract (AHE) affects the peripheral artery disease in diabetic rats through lowering of advanced glycation end products (AGEs). The in-vitro AGE inhibiting potential of AHE was determined by spectrofluorimetric method. The blood glucose levels and HbA1c (A1C) of the rats from each group were determined by automatic analyser. The levels of AGEs in vascular smooth muscle cells (VSMCs) of different rat groups were observed through western blotting. Expression of COX-1 and COX-2 were determined by qRT-PCR. The AHE inhibition of AGEs formation was reported in vitro and exhibited an IC50 of 45 μg/mL which was significantly lower than that of standard AGEs inhibitor aminoguanidine (IC50: 60 μg/mL). Analysis of metabolic profiles revealed that AHE normalised the blood glucose, cholesterol, and triglycerides with no apparent changes on Hb1Ac levels. Western blot analysis showed that AHE exhibited protective effects in VSMCs of diabetic rats by inhibiting fabrication of AGEs. Moreover, the manifestation of COX-2 was inhibited by AHE in diabetic rats. However, the expression of COX-1 remained unaltered. Collectively, the results revealed AHE inhibits AGEs formation in vitro and in VSMCs of diabetic rats. These findings point towards the prospective of AHE applications towards the management of diabetic peripheral artery disease.

A Simple and Straightforward Linear Approximation Model of Predicting the Glucose and HbA1C Values to Manage Type 2 Diabetes Based on GH-Method: Math-Physical Medicine (No. 472)

Based on research work over 6.5 years, the author summarized his work results into a set of simple and straightforward linear model to predict approximate, but accurate enough, sensor glucose and HbA1C values. It utilizes both of the linear elastic glucose theory (LEGT) from strength of engineering materials and the first-order interpolation perturbation theory (perturbation) from quantum mechanics to construct various PPG waveforms. To start, he measures his weight in early morning, next he estimates his fasting plasma glucose (FPG) at his wakeup moment, then approximates his breakfast post-prandial plasma glucose (PPG) at 0-minute time instant, and finally applies either LEGT model or perturbation model to construct his daily PPG waveform over a three-hours timeframe. Based on the estimated FPG value and three PPG values, he can then assess his daily average sensor glucose (eAG) and HbA1C (A1C) value on that particular day.

Positivity and indicators of health among African Americans with diabetes.

To examine the utility of the positivity ratio to distinguish differences in psychological and physiological health in African Americans with type 2 diabetes. Study participants (N = 93) were recruited through radio and church announcements and grouped by their positivity ratio. Multivariate analyses showed flourishing individuals had the highest resilience and lowest depressive symptoms and HbA1c (A1C), whereas depressed individuals recorded the lowest resilience and highest depressive symptoms and A1C. Small to large effect sizes were reported. Further support for the utility and generalizability of the positivity ratio was provided. Cultivating positive emotions may improve the health of individuals with type 2 diabetes.

Screening for HbA1c-defined prediabetes and diabetes in an at-risk greek population: Performance comparison of random capillary glucose, the ADA diabetes risk test and skin fluorescence spectroscopy

BackgroundWe examined the accuracy of random capillary glucose (RCG) and two noninvasive screening methods, the ADA diabetes risk test (DRT) and skin fluorescence spectroscopy (SFS) as measured by Scout DS for detecting HbA1c-defined dysglycemia or type 2 diabetes in an at-risk cohort. MethodsSubjects were recruited at two clinical sites for a single non-fasting visit. Each subject had measurements of height, weight and waist circumference. A diabetes score was calculated from skin fluorescence measured on the left forearm. A finger prick was done to measure RCG and HbA1c (A1C). Health questionnaires were completed for the DRT. Increasing dysglycemia was defined as A1C≥5.7% (39mmol/mol) or ≥6.0% (42mmol/mol). Type 2 diabetes was defined as A1C≥6.5% (47.5mmol/mol). Results398 of 409 subjects had complete data for analysis with means for age, body mass index, and waist of 52 years, 27kg/m2 and 90cm. 51% were male. Prevalence of A1C≥5.7%, ≥6.0% and ≥6.5% were 54%, 34% and 12%, respectively. Areas under the curve (AUC) for detection of increasing levels dysglycemia or diabetes for RCG were 63%, 66% and 72%, for the ADA DRT the AUCs were 75%, 76% and 81% and for SFS the AUCs were 82%, 84% and 90%, respectively. For each level of dysglycemia or diabetes, the SFS AUC was significantly higher than RCG or the ADA DRT. ConclusionsThe noninvasive skin fluorescence spectroscopy measurement outperformed both RCG and the ADA DRT for detection of A1C-defined dysglycemia or diabetes in an at-risk cohort.

Long-Term Metformin Use Is Associated With Decreased Risk of Breast Cancer

OBJECTIVETo evaluate whether use of oral hypoglycemic agents is associated with an altered breast cancer risk in women.RESEARCH DESIGN AND METHODSUsing the U.K.-based General Practice Research Database, we conducted a nested case-control analysis among 22,621 female users of oral antidiabetes drugs with type 2 diabetes. We evaluated whether they had an altered risk of breast cancer in relation to use of various types of oral hypoglycemic agents. Case and control patients with a recorded diagnosis of type 2 diabetes were matched on age, calendar time, and general practice, and the multivariate conditional logistic regression analyses were further adjusted for use of oral antidiabetes drugs, insulin, estrogens, smoking BMI, diabetes duration, and HbA1c (A1C).RESULTSWe identified 305 case patients with a recorded incident diagnosis of breast cancer. The mean ± SD age was 67.5 ± 10.5 years at the time of the cancer diagnosis. Long-term use of ≥40 prescriptions (>5 years) of metformin, based on 17 exposed case patients and 120 exposed control patients, was associated with an adjusted odds ratio of 0.44 (95% CI 0.24–0.82) for developing breast cancer compared with no use of metformin. Neither short-term metformin use nor use of sulfonylureas or other antidiabetes drugs was associated with a materially altered risk for breast cancer.CONCLUSIONSA decreased risk of breast cancer was observed in female patients with type 2 diabetes using metformin on a long-term basis.

Translating the A1C Assay

In the clinical management of diabetes, the A1C assay has become indispensable. Used worldwide to monitor chronic glycemia, the assay is an essential tool to determine whether a patient has achieved the core goal of therapy for diabetes: a marked and sustained reduction in plasma glucose to achieve as close to a normal level as can be safely attained. With the publication of the A1c-Derived Average Glucose (ADAG) study in this issue of Diabetes Care (1), the evolution of the A1C assay continues and an important milestone has been reached. To better appreciate this recent report, a brief and admittedly incomplete historical perspective may be useful. It was 60 years ago that Allen et al. (2) showed that hemoglobin A (which makes up about 97% of total hemoglobin) contains three minor components, designated HbA1a, HbA1b, and HbA1c (A1C). In the decades that followed, we learned that a hexose molecule is attached to these components (3) and that hemoglobin A actually has two more minor glycated derivatives. The five altogether comprise ∼5–7% of the HbA molecule (4). In the early course of the biochemical dissection of hemoglobin, Huisman and Dozy (5) noted, virtually in passing, that the level of glycated hemoglobin components was increased in a few individuals they studied who happened to have diabetes. It took 4 more years, however, for Rahbar and colleagues (6,7) to document that diabetes is clearly associated with an elevation in glycated hemoglobin. The Rahbar reports stimulated other investigators to confirm these initial findings and to seek an explanation for how glucose binds to hemoglobin. It was not for another few years, in 1972, that Bunn et al. (8) elegantly showed that the cause of the increased glycated hemoglobin in diabetes, which was predominantly the A1C component, …

Serum and Urinary Nitrites and Nitrates and Doppler Sonography in Children With Diabetes

The aim of the present study was to evaluate serum and urinary nitric oxide (NO) concentrations in children and adolescents with diabetes compared with age-matched healthy control subjects to find out whether Doppler ultrasonography could be used to detect changes in renal resistive indexes (RIs) in children with diabetes and to assess whether there are correlations between these parameters and NO excretion. We studied 42 children with type 1 diabetes and 41 matched healthy control subjects, both divided into prepubertal or pubertal children. Serum and urinary nitrite and nitrate (NO2-+NO3-) concentrations were evaluated as an index of NO production. Doppler ultrasonographic registration of intrarenal RI was performed. Compared with healthy control subjects, children with diabetes had significantly increased concentrations of serum (30.26 +/- 6.52 vs. 24.47 +/- 7.27 mmol/l, P = 0.001) and urinary NO2-+NO3- (345.07 +/- 151.35 vs. 245.86 +/- 80.25 mmol/l, P = 0.002); the same was true for Doppler RI values (0.64 +/- 0.03 vs. 0.60 +/- 0.04, P = 0.035). This occurs in both prepubertal and the pubertal children. A significant positive correlation was found between serum and urinary NO2-+NO3- levels (P = 0.002, r = 0.374). Serum NO2-+NO3- concentrations also correlated positively with Doppler RI (P = 0.032, r = 0.262) and HbA1c (A1C) (P = 0.004, r = 0.329); urinary NO2-+NO3- concentrations correlated positively with A1C (P = 0.001, r = 0.394). Doppler RI correlated positively with A1C (P = 0.000, r = 0.424). This study demonstrates that in children with diabetes, chronic hyperglycemia may act through a mechanism that involves increased NO production and/or action and contributes to generating intrarenal hemodynamic abnormalities, which are detectable by Doppler ultrasonography even in early diabetic nephropathy.

Immunoneutralization of Endogenous Glucagon Reduces Hepatic Glucose Output and Improves Long-Term Glycemic Control in Diabetic ob/ob Mice

In type 2 diabetes, glucagon levels are elevated in relation to the prevailing insulin and glucose levels. The relative hyperglucagonemia is linked to increased hepatic glucose output (HGO) and hyperglycemia. Antagonizing the effects of glucagon is therefore considered an attractive target for treatment of type 2 diabetes. In the current study, effects of eliminating glucagon signaling with a glucagon monoclonal antibody (mAb) were investigated in the diabetic ob/ob mouse. Acute effects of inhibiting glucagon action were studied by an oral glucose tolerance test (OGTT) and by measurement of HGO. In addition, the effects of subchronic (5 and 14 days) glucagon mAb treatment on plasma glucose, insulin, triglycerides, and HbA1c (A1C) levels were investigated. Glucagon mAb treatment reduced the area under the curve for glucose after an OGTT, reduced HGO, and increased the rate of hepatic glycogen synthesis. Glucagon mAb treatment for 5 days lowered plasma glucose and triglyceride levels, whereas 14 days of glucagon mAb treatment reduced A1C. In conclusion, acute and subchronic neutralization of endogenous glucagon improves glycemic control, thus supporting the contention that glucagon antagonism may represent a beneficial treatment of diabetes.

Poor Glucose Control in the Year Before Admission as a Powerful Predictor of Amputation in Hospitalized Patients With Diabetic Foot Ulceration

Although there is a strong association between lower-extremity amputation (LEA) and HbA1c (A1C) in diabetic patients (1,2), little information is available on glucose control in the period preceding and following LEA (3). Our objective was to evaluate the predictors of LEA and to examine the role of blood glucose control during the year before and the year after admission. A total of 122 diabetic patients (82 men and 40 women aged 69.7 ± 10.9 years, disease duration 19.7 ± 10.4 years) consecutively admitted for diabetic foot ulcers to the Medicine Department of United Hospitals of Bergamo between January 2003 and December 2004 were enrolled in our observational study and assigned to one …

Cytotoxin-Associated Gene A Strains ofHelicobacter PyloriRepresent a Risk Factor for the Development of Microalbuminuria in Type 2 Diabetes

The reasons why diabetic patients with microalbuminuria have marked endothelial damage (1,2) and an increased risk of atherosclerosis (3,4) are unclear. Infection with Helicobacter pylori , especially with strains carrying the cytotoxin-associated gene A (CagA), might represent a causal factor, since anti-CagA antibodies elicited by infection may cross-react with endothelial antigens (5), increasing the vascular damage associated with diabetes itself and consequent albumin leakage. Furthermore, infection might induce a persistent systemic inflammatory response, which is a recognized risk factor for atherosclerosis (6). In this study, we investigated the possible pathogenetic role of CagA-positive H. pylori strains in type 2 diabetic patients with microalbuminuria. Consecutive ambulatory patients with a known history of type 2 diabetes who were ≥40 years of age were considered. Data on age, sex, BMI, smoking habit, history of hypertension or hyperlipidemia, disease duration, previous myocardial infarction, previous stroke, and HbA1c (A1C) were collected. Serum level of C-reactive protein (CRP), a marker of systemic inflammation, was measured only in patients without obvious inflammatory conditions. Exclusion criteria were presence of renal failure (creatinine >133 μmol/l), previous H. pylori eradication, and evidence of connective tissue, neoplastic, or hematological disease. Since virtually all peptic ulcers are due to H. pylori (7), and most of them to CagA-positive strains (8), a history of …

A Low Brain Serotonergic Neurotransmission in Children With Type 1 Diabetes Detected Through the Intensity Dependence of Auditory-Evoked Potentials

OBJECTIVE—To determine in children with type 1 diabetes the plasma free fraction of l-tryptophan (FFT) and the intensity-dependent auditory-evoked potentials (IDAEPs) as indicators of possible changes in brain serotonergic neurotransmission. RESEARCH DESIGN AND METHODS—A prospective and comparative study was performed in children with type 1 diabetes and normal control subjects. We measured FFT, bound and total plasma l-tryptophan, neutral amino acids (NAAs), albumin, free fatty acids (FFAs), glucose, and HbA1c(A1C) and recorded IDAEPs with four intensities (40, 60, 90, and 103 dB). RESULTS—The glycemia, A1C, FFAs, and NAAs in plasma were significantly elevated. The FFT and the FFT-to-total l-tryptophan and FFT-to-NAA ratios were reduced. The latencies of N1 and P2 increased at all intensities and the slope of the amplitude/stimulus intensity function (ASF slope) of the N1/P2 component significantly increased. CONCLUSIONS—The decrease of the FFT in plasma and increase in the N1/P2 component amplitude may reflect a functional relationship between the brain serotonergic activity with the N1/P2 changes. The increase of the ASF slope in children with type 1 diabetes suggests that the response of the auditory cortex to sound intensity stimulus may be regulated by the serotonergic tone and that decreased serotonergic neurotransmission may provoke a different behavior of sensory cortices. Therefore, the IDAEP (N1/P2 component) may be an electrophysiological indicator of brain changes of serotonergic neurotransmission in children with type 1 diabetes. These changes may be related to psychoemotional manifestations observed in diabetic children such as anxiety and depression.

A Low Brain Serotonergic Neurotransmission in Children With Type 1 Diabetes Detected Through the Intensity Dependence of Auditory-Evoked Potentials

To determine in children with type 1 diabetes the plasma free fraction of L-tryptophan (FFT) and the intensity-dependent auditory-evoked potentials (IDAEPs) as indicators of possible changes in brain serotonergic neurotransmission. A prospective and comparative study was performed in children with type 1 diabetes and normal control subjects. We measured FFT, bound and total plasma L-tryptophan, neutral amino acids (NAAs), albumin, free fatty acids (FFAs), glucose, and HbA1c(A1C) and recorded IDAEPs with four intensities (40, 60, 90, and 103 dB). The glycemia, A1C, FFAs, and NAAs in plasma were significantly elevated. The FFT and the FFT-to-total L-tryptophan and FFT-to-NAA ratios were reduced. The latencies of N1 and P2 increased at all intensities and the slope of the amplitude/stimulus intensity function (ASF slope) of the N1/P2 component significantly increased. The decrease of the FFT in plasma and increase in the N1/P2 component amplitude may reflect a functional relationship between the brain serotonergic activity with the N1/P2 changes. The increase of the ASF slope in children with type 1 diabetes suggests that the response of the auditory cortex to sound intensity stimulus may be regulated by the serotonergic tone and that decreased serotonergic neurotransmission may provoke a different behavior of sensory cortices. Therefore, the IDAEP (N1/P2 component) may be an electrophysiological indicator of brain changes of serotonergic neurotransmission in children with type 1 diabetes. These changes may be related to psychoemotional manifestations observed in diabetic children such as anxiety and depression.

Age-Specific Advantages of Continuous Subcutaneous Insulin Infusion as Compared With Multiple Daily Injections in Pediatric Patients: One-year follow-up comparison by matched-pair analysis

In the past years, treatment with continuous subcutaneous insulin infusion (CSII) has been increasingly used in younger age-groups of patients with type 1 diabetes, and several studies have reported advantages of CSII, but little information is based on case-controlled analyses (1,2). Although short-term effects of CSII were described (3), there is no clear evidence whether its use leads to a continuous improvement of glycemic control. In order to evaluate long-term effects, we performed a matched-pair analysis comparing the outcome in young patients with CSII versus multiple daily injection (MDI) over 1 year of treatment under routine conditions representative of a pediatric diabetes clinic. Fifty-nine of 85 patients starting on CSII from 2001 to 2004 with treatment duration of at least 1 year were eligible. The control cohort was comprised of 580 patients treated with MDI within the same time period. Fifty-two matched pairs could be identified fulfilling the matching criteria: sex, age (± 1 year), diabetes duration (± 1 year), and HbA1c (A1C) level (± 0.3%) at study entry (start of CSII). In the case of multiple matched MDI subjects, only the subject closest to A1C and diabetes duration was selected. Patients with MDI received treatment based on the basal-bolus principle and had 3.5 ± 0.9 injections per day. Forty-one patients (79%) used NPH, eight …

Age-Specific Advantages of Continuous Subcutaneous Insulin Infusion as Compared With Multiple Daily Injections in Pediatric Patients

In the past years, treatment with continuous subcutaneous insulin infusion (CSII) has been increasingly used in younger age-groups of patients with type 1 diabetes, and several studies have reported advantages of CSII, but little information is based on case-controlled analyses (1,2). Although short-term effects of CSII were described (3), there is no clear evidence whether its use leads to a continuous improvement of glycemic control. In order to evaluate long-term effects, we performed a matched-pair analysis comparing the outcome in young patients with CSII versus multiple daily injection (MDI) over 1 year of treatment under routine conditions representative of a pediatric diabetes clinic. Fifty-nine of 85 patients starting on CSII from 2001 to 2004 with treatment duration of at least 1 year were eligible. The control cohort was comprised of 580 patients treated with MDI within the same time period. Fifty-two matched pairs could be identified fulfilling the matching criteria: sex, age (± 1 year), diabetes duration (± 1 year), and HbA1c (A1C) level (± 0.3%) at study entry (start of CSII). In the case of multiple matched MDI subjects, only the subject closest to A1C and diabetes duration was selected. Patients with MDI received treatment based on the basal-bolus principle and had 3.5 ± 0.9 injections per day. Forty-one patients (79%) used NPH, eight …

Biofeedback-Assisted Relaxation in Type 2 Diabetes

The objective of this randomized controlled study was to determine the effects of biofeedback and relaxation on blood glucose and HbA1c (A1C) in patients with type 2 diabetes. Patients with type 2 diabetes were randomized to either 10 sessions of biofeedback (electromyograph and thermal) and relaxation or 3 sessions of education. All sessions were individual. A total of 39 participants were entered, and 30 completed the 3-month protocol. Average blood glucose, A1C, forehead muscle tension, and peripheral skin temperature were assessed, and inventories measuring depression and anxiety were administered pre-randomization and after completion of treatment/control. Biofeedback and relaxation were associated with significant decreases in average blood glucose, A1C, and muscle tension compared with the control group. At 3-month follow-up, the treatment group continued to demonstrate lower blood glucose and A1C. Both groups decreased scores on the depression and anxiety inventories. Patients with depression had higher blood glucose levels and tended to drop out of the study. This study supports the use of biofeedback and relaxation in patients with type 2 diabetes for up to 3 months after treatment. Further research is necessary to determine the long-term effects of biofeedback and the effects of mood on patients' responses to treatment.

Web-Based Care Management in Patients With Poorly Controlled Diabetes

To assess the effects of web-based care management on glucose and blood pressure control over 12 months in patients with poorly controlled diabetes. For this study, 104 patients with diabetes and HbA(1c) (A1C) > or =9.0% who received their care at a Department of Veterans Affairs medical center were recruited. All participants completed a diabetes education class and were randomized to continue with their usual care (n = 52) or receive web-based care management (n = 52). The web-based group received a notebook computer, glucose and blood pressure monitoring devices, and access to a care management website. The website provided educational modules, accepted uploads from monitoring devices, and had an internal messaging system for patients to communicate with the care manager. Participants receiving web-based care management had lower A1C over 12 months (P < 0.05) when compared with education and usual care. Persistent website users had greater improvement in A1C when compared with intermittent users (-1.9 vs. -1.2%; P = 0.051) or education and usual care (-1.4%; P < 0.05). A larger number of website data uploads was associated with a larger decline in A1C (highest tertile -2.1%, lowest tertile -1.0%; P < 0.02). Hypertensive participants in the web-based group had a greater reduction in systolic blood pressure (P < 0.01). HDL cholesterol rose and triglycerides fell in the web-based group (P < 0.05). Web-based care management may be a useful adjunct in the care of patients with poorly controlled diabetes.

Is Physician Gender Associated With the Quality of Diabetes Care?

This study examines the association between physician gender and diabetes quality of care. We examined the association between the gender of primary care physicians (n = 1,686) and the quality of diabetes care they provided to their patients participating in the Translating Research Into Action for Diabetes (TRIAD) study. Main outcome measures were diabetes processes of care including receipt of dilated retinal exams, urine microalbumin/protein testing, foot exams, lipid and HbA(1c) (A1C) testing, recommendation to take aspirin, and influenza vaccination over 1 year. Intermediate outcomes included blood pressure, A1C, LDL levels, and patient satisfaction. Hierarchical regression models accounted for clustering within provider groups and health plans and adjusted for patient age, gender, race, income, education, diabetes treatment and duration, and health status, along with physician age, years of practice, and specialty. Compared with male physicians (n = 1,213), female physicians (n = 473) were younger, had more recently completed training, and were more often internists. Patients of female physicians (n = 4,585) were more often women and younger than patients of male physicians (n = 1,783). In adjusted analyses, patients of female physicians were slightly more likely to receive lipid measurements (predicted probability 1.09 [95% CI 1.02-1.15]) and A1C measurements (1.02 [1.00-1.05]) and were slightly more likely to have an LDL <130 mg/dl (1.05 [1.00-1.10]). Patients of female physicians received similar quality of care compared with patients of male physicians.

The Early Natural History of Nephropathy in Type 1 Diabetes

Predictors of albumin excretion rate (AER) abnormalities could provide earlier indicators of diabetic nephropathy risk. Data from the Natural History Study, a prospective 5-year observation of renal structure and function in young type 1 diabetic patients, were examined for predictors of AER patterns in normoalbuminuric type 1 diabetic patients. Included were 170 patients (96 females) (aged 16.7 +/- 5.9 years, duration of diabetes 8.0 +/- 4.3 years) with normal blood pressure, normoalbuminuria (AER <20 microg/min), and eight or more follow-up visits over 5 years. AER, blood pressure, and HbA1c (A1C) were determined quarterly and glomerular filtration rate (GFR) annually. Persistent microalbuminuria (PMA) was defined as 20-200 microg/min in two of three consecutive values within 6-12 months. Four different AER patterns were identified. Group 1 (n = 99): all values <20 microg/min. Group 2 (n = 49): intermittent levels >20 microg/min but not meeting microalbuminuria criteria. Group 3 (n = 14): PMA during follow-up but normoalbuminuria at study exit. Group 4 (n = 8): microalbuminuria at study exit. Group 4 (497 +/- 95 nm, P < 0.01) and group 3 (464 +/- 113 nm, P = 0.03) patients had greater baseline glomerular basement membrane (GBM) width versus group 1 (418 +/- 67 nm). Baseline GFR in group 4 (163 +/- 37 ml.min(-1). 1.73 m(-2)) was higher than group 1 (143 +/- 28 ml.min(-1) . 1.73 m(-2), P = 0.04). A1C was higher in group 2 (9.0 +/- 1.2%) than group 1 (8.4 +/- 1.1%, P = 0.008). Thus, greater increases in GBM width and GFR were predictors of PMA. Since 64% of the patients that developed microalbuminuria reverted to normoalbuminuria, the risk of diabetic nephropathy as defined by current microalbuminuria criteria is unclear.