Self-Management Support Improves Diabetes Outcomes Without Exacerbating Inequities.

INTRODUCTION: Previous research has found an association between low health literacy and poor clinical outcomes in type 2 Diabetes Mellitus (T2DM) patients. We sought to determine if this association can be mitigated by a self-management support (SMS) program provided by trained health workers using a technology assisted menu driven program, called Connection to Health (CTH). METHODS: This study is a secondary analysis from a randomized trial of 2 similar versions of CTH implemented in 12 Northern California community health centers. As part of this, each participant completed a single validated question to assess health literacy. We used unadjusted and adjusted linear regression analyses to determine the extent to which baseline health literacy was predictive of prepost changes in hemoglobin A1c (HbA1c). RESULTS: Of 365 participants for whom prepost HbA1c data were available, HbA1c concentrations declined by an average of 0.76% (from 9.9% to 9.2%, 95% CI (0.53%-1.0%). Almost 114 (31.2%) of the participants had low health literacy, but there was no significant association between health literacy and the reduction in HbA1c concentrations in either the unadjusted or adjusted models, nor did baseline health literacy predict prepost changes in body mass index, medication adherence, exercise, or diet. DISCUSSION: The study found that implementing the CTH program in 2 versions via a randomized clinical trial improved HbA1c concentrations without increasing disparities between participants with high and low health literacy. This suggests CTH-like programs can enhance diabetes outcomes in community health centers without exacerbating inequities for those with low health literacy.

Hb Hebei [α20 (B1) His→Leu; HBA2:C.62A > T]: A Novel Hemoglobin Variant Found during Measurement of Glycated Hemoglobin.

We report a novel hemoglobin (Hb) variant found in a 34-year-old Chinese male during a routine measurement of glycated hemoglobin. The variant resulted in a P3 peak of 27.5% of the total Hb on high performance liquid chromatography (HPLC) with a glycated hemoglobin mode. However, no abnormal Hb peaks were observed in capillary electrophoresis (CE) with 3.1% Hb A2 and 96.9% Hb A. The amino acid substitution was determined by Sanger sequencing as α20 (B1) His→Leu; the corresponding DNA mutation was identified as CAC > CTC at the first position of codon 20 of the α-chain. This is the first description of the mutation, and we have named it Hb Hebei for the region of origin of the proband.

A New Hemoglobin Variant: Hb Tangshan [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)] Detected by MALDI-TOF MS.

In this report we decribed a new α-chain variant found during the measurement of hemoglobin A1c (Hb A1c) using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS). MALDI-TOF MS analysis detected an α-chain variant with a mass of 15,155 Da. However, this Hb variant was not detected during Hb A1c measurement by cation-exchange high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) methods. Sanger sequencing validated the presence of a heterozygous missense mutation [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)]. The observed 28 Da mass difference exactly matches the theoretical mass difference (28 Da) resulting from the substitution of alanine (89.079) with valine (117.133). As this represents the initial documentation of the mutation, we named it Hb Tangshan after the proband's residence.

The dual inhibitor Sacubitril-valsartan ameliorate high-fat high-fructose-induced metabolic disorders in rats superiorly compared to valsartan only.

OBJECTIVES: Sacubitril-valsartan, a recently approved treatment for heart failure, has shown some promise as a possible therapeutic option for diabetes mellitus. It is still not clear whether those beneficial effects are comparable to valsartan effects. In this work, we aimed at investigating Sacubitril-valsartan effect on metabolic changes in a model of high-fat high fructose diet-induced diabetes mellitus, in comparison to the metabolic changes induced by valsartan only. METHODS: Rats were ad libitum fed with either standard chow plus tap water for drinking (controls) or 60% beef tallow and 10% fructose drinking water (diseased) for 11 weeks. Starting in week 9, each group was subdivided into four, namely vehicle, pioglitazone, Sacubitril-valsartan and valsartan. Treatments were administered from weeks 9 to 11, while rats were maintained in their respective diet groups. KEY FINDINGS: Sacubitril-valsartan treatment significantly decreased daily food intake, body weight and epididymal white adipose weight, and normalized insulin and glycosylated haemoglobin in high-fat high fructose. Both valsartan and Sacubitril-valsartan only attenuated the elevated fasting blood glucose levels, glucose, insulin and pyruvate tolerance and increased protein kinase B phosphorylation in diseased rats. CONCLUSIONS: Sacubitril-valsartan may be an effective modulator of diabetes mellitus-associated metabolic aberration, superiorly compared to valsartan only.

A Statistical Simulation to Evaluate the Robustness of Hb A1c Measurement in the Presence of Quantitative Error.

BACKGROUND: The performance requirements for hemoglobin (Hb) A1c analysis have been questioned as analytic methods have improved. We developed a statistical simulation that relates error to the clinical utility of an oft-used laboratory test, as a means of assessing test performance expectations. METHODS: Finite mixture modeling of the Centers for Disease Control and Prevention-National Health and Nutrition Examination Survey (NHANES) 2017-2020 Hb A1c data in conjunction with Monte Carlo sampling were used to model and simulate a population prior to the introduction of error into the results. The impact of error on clinical utility was assessed by categorizing the results using the American Diabetes Association (ADA) diagnostic criteria and assessing the sensitivity and specificity of Hb A1c under various degrees of error (bias and imprecision). RESULTS: With the current allowable total error threshold of 6% for Hb A1c measurement, the simulation estimated a worst case between 50% and 60% for both test sensitivity and specificity for the non-diabetic category. Similarly, sensitivity and specificity estimates for the pre-diabetic category were 30% to 40% and 60% to 70%, respectively. Finally, estimates for the diabetic category yielded values of 80% to 90% for sensitivity and >90% for specificity. CONCLUSIONS: Bias and imprecision greatly affect the clinical utility of Hb A1c for all patient groups. The simulated error demonstrated in this modeling impacts 3 critical applications of the Hb A1c in diabetes management: the capacity to reliably screen, diagnostic accuracy, and utility in diabetes monitoring.

Hb Alessandria [ß37(C3)Trp→Leu; HBB: c.113G>T]: a Novel Variant on the ß-Globin Chain with Slightly Increased Affinity for Oxygen Detected by Capillary Electrophoresis.

We report a novel mutation on the ß-globin gene in a 68-year-old woman of Sicilian origin living in Alessandria, Italy. This mutation produces a hemoglobin (Hb) variant of Hb A that was detected by the capillary electrophoresis (CE) method during measurement of Hb A1c. The variant Hb did not separate from Hb A using different high performance liquid chromatography (HPLC) instruments. Direct DNA sequencing revealed a G>T transversion at codon 37 and subsequent substitution of a tryptophan residue for a leucine residue. The new Hb variant was named Hb Alessandria [ß37(C3)Trp→Leu; HBB: c.113G>T]. The p50 value was slightly decreased while the stability test at 37 °C in isopropyl alcohol and the main erythrocyte parameters were normal. Overall, the patient appeared clinically normal.

Hb Kirikiriroa [α57(E6)Gly→Cys; HBA1: c.172G>T]: A Novel Unstable α-Globin Variant with Oxidized Derivatives Interfering with Hb A1c.

We report the identification of a novel hemoglobin (Hb) variant [α57(E6)Gly→Cys; HBA1: c.172G>T], to be referred to as Hb Kirikiriroa. The variant was detected in five subjects from two families, with familial relationship established between the families following diagnosis. A persistently elevated Hb A1c over a 1-year period prompted hemoglobinopathy screening in an adolescent male of New Zealand (NZ) European descent (case 1). Capillary electrophoresis (CE) revealed the variant was negatively charged and susceptible to oxidation, with multiple abnormal peaks detected (0.4-5.1% total Hb). Hb A1c analysis by cation exchange high performance liquid chromatography (HPLC) was the first indication of the variant in a pregnant female of NZ European descent (case 2). Cases 1 and 2 had normal complete blood counts. Isopropanol stability testing provided evidence the variant was unstable. We herein describe the characterization of Hb Kirikiriroa and clinical significance of the variant for interference with Hb A1c analysis by CE and cation exchange HPLC.

Hb Kalundborg [ß79(EF3)Asp→Glu; HBB: c.240C>a], a Possible Low-affinity Hemoglobin Variant Detected during Hb A1c Measurement.

A previously unknown hemoglobin (Hb) variant was detected during measurement of glycosylated Hb (Hb A1c) after the introduction of a new high performance liquid chromatography (HPLC) apparatus. Subsequent DNA sequencing revealed a heterozygous single nucleotide substitution at codon 79 (C>A) on the ß-globin gene changing an amino acid [ß79(EF3)Asp→Glu; HBB: c.240C>A]. The new Hb variant was named Hb Kalundborg after the place of origin of the proband. Heterozygosity for this mutation appears to have no clinical significance in itself except for a possibly slightly lower oxygen affinity. However, it interferes with Hb A1c measurement by HPLC, causing a falsely high Hb A1c concentration when using the G11 apparatus with clinical implications possibly to follow.

A New Case of Hb Headington (HBB: c.217A>C) Due to a New DNA Transversion, Found in a Patient with Type 2 Diabetes Mellitus.

We here report a novel case of Hb Headington [ß72(E16)Ser→Arg, HBB: c.217A>C, p.Ser73Arg], in a 68-year-old woman with type 2 diabetes mellitus (T2DM). Glycosylated hemoglobin (Hb) was measured by capillary electrophoresis (CE). The spectrum showed abnormal peaks between the A0 and A2 peaks. DNA sequencing demonstrated a mutation on the HBB gene, which predicted a substitution of serine to arginine at position 73 in the ß-globin chain. Moreover, this amino acid substitution occurs at the same position as Hb Headington [ß72(E16)Ser→Arg, HBB: c.219T>A, p.Ser73Arg], which showed increased oxygen affinity.

Longitudinal progression of diabetes mellitus in Wolfram syndrome: The Washington University Wolfram Research Clinic experience.

OBJECTIVE: (1) Describe the progression of diabetes mellitus over time in an observational study of Wolfram syndrome, a rare, genetic, neurodegenerative disorder, which often includes diabetes mellitus and is typically diagnosed during childhood or adolescence. (2) Determine whether C-peptide could be used as a marker of diabetes progression in interventional trials for Wolfram syndrome. METHODS: N = 44 (25F/19M) participants with genetically confirmed Wolfram syndrome attended the Washington University Wolfram Research Clinic annually from 2010 to 2019. Medical history, physical examinations, blood sampling, and questionnaires were used to collect data about diabetes mellitus and other components of Wolfram syndrome. Beta-cell function was assessed by determination of C-peptide during a mixed meal tolerance test. Random coefficients models evaluated the rate of progression of C-peptide over time, and power analyses were used to estimate the number of subjects needed to detect a change in C-peptide decline during an intervention trial. RESULTS: 93.2% of patients had diabetes mellitus. Mean HbA1c across all study visits was 7.9%. C-peptide significantly decreased with increasing duration of diabetes mellitus (p < 0.0001); an optimal break point in C-peptide decline was identified to occur between 0.1 and 2.3 years after diabetes mellitus diagnosis. Twenty patients per group (active vs. control) were estimated to be needed to detect a 60% slowing of C-peptide decline during the first 2.3 years following diabetes diagnosis. CONCLUSION: C-peptide declines over time in Wolfram syndrome and could potentially be used as a marker of diabetes progression in interventional studies for Wolfram syndrome, especially within the first 2 years after diabetes diagnosis.

Hb Jishui [HBA1: c.225C>G, Codon 74 (GAC>GAG), Asp→Glu]: A Novel α Chain Hemoglobin Variant Detected During Hb A1c Measurement.

Here we report a novel α chain hemoglobin (Hb) variant found in a 74-year-old Chinese male. We accidentally discovered this Hb variant during the measurement of Hb A1c by a capillary electrophoresis (CE) method (Hb A1c program, CapillaryS3 TERA). However, Hb analysis with the Hb program of CapillaryS3 TERA and the VARIANT II™ ß-Thalassemia Short Program showed no indication of the Hb variant. Sanger sequencing revealed a new missense mutation on the HBA1 gene [HBA1: c.225C>G, codon 74 (GAC>GAG), Asp→Glu]. We named it Hb Jishui after the birthplace of the proband.

Impact of diabetes mellitus on outcome after transcatheter aortic valve replacement: Identifying high-risk diabetic population from the OCEAN-TAVI registry.

OBJECTIVES: To identify the vulnerable diabetic cohort in patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUNDS: Considerable controversy remains about whether specific cohort exists in which presence of diabetes mellitus (DM) carries adverse risk of mortality after TAVR. METHODS: Of the 2588 patients who were enrolled in the OCEAN-TAVI registry, 2526 patients with glycohemoglobin data were analyzed. The individuals were divided into DM and non-DM groups according to previous medical history of DM or using diabetic medicine, and increased HbA1c values (≥6.5%) at baseline. The primary endpoint of this study was 2-year all-cause mortality after TAVR. RESULTS: The follow up rate of clinical outcome at 1-year was 2514/2526 (99.5%) and median follow-up period was 22.5 months. DM group had 699 (27.7%) patients, in which 153 (21.9%) was diagnosed by increased HbA1c levels without previous medical history of DM. Kaplan-Meier curve of 2-year all-cause mortality presented significant difference between patients with and without DM (p = 0.029). In addition, patients with low-density lipoprotein cholesterol (LDL-C) levels > 100 mg/dl and left ventricular ejection fraction (LVEF) < 40% had great risk of mortality after TAVR (LDL-C: hazard ratio [HR] 1.82, p < 0.001; LVEF: HR 2.61, p = 0.002, respectively). CONCLUSIONS: Presence of DM was significantly associated with poor outcome after TAVR and adverse effect of DM was remarkable in patients with relatively higher LDL-C levels and reduced LVEF under 40%. These subtypes may need intensive control of cardiovascular risk factors, including DM, before and after TAVR.

Hb A2-Calderdale [δ2(NA2)His→Asn; HBD: c.7C>A] and Misdiagnosis of Type 2 Diabetes Mellitus Due to Interference with Hb A1c When Using Cation Exchange High Performance Liquid Chromatography: A Case Report.

The Hb A2-Calderdale variant [δ2(NA2)His→Asn, HBD: c.7C>A] was described as a novel variant in 2014. However, a high performance liquid chromatography (HPLC) peak was never identified indicating that this fraction could be 'hiding' somewhere else in the chromatogram. In this case report, we present evidence that the physiochemical properties of Hb A2-Calderdale resemble those of Hb A1c, resulting in a coelution in variant mode on the Tosoh G8 but not the Tosoh G11. This coelution results in an overestimation of Hb A1c and can potentially cause misdiagnosis of type 2 diabetes mellitus (T2DM).

A Novel α-Globin Chain Variant, Hb Nanchang [HBA2: c.46G>A, Codon 15 (GGT>AGT) (Gly→Ser)], Detected by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

Here we report a new α chain variant accidentally discovered during Hb A1c measurement by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) that revealed the presence of a variant α chain with a mass of 15155 Da. However, this hemoglobin (Hb) variant cannot be detected by the first-line methods such as cation exchange high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Sanger sequencing confirmed the presence of a heterozygous missense mutation [HBA2: c.46G>A, codon 15 (GGT>AGT), (Gly→Ser)]. The theoretical mass difference (30 Da) due to the substitution of amino acid glycine to serine matched the actual measured mass difference (29 Da). As this is the first report of the mutation, we named it Hb Nanchang after the place of residence of the proband.

Association between Hb A1c and Severity of COVID-19 Patients.

This study aimed to examine the relationship between Hb A1c levels and the clinical course of coronavirus-19 (COVID-19) patients. Sixty-six COVID-19(+) patients with high Hb A1c and 46 with average Hb A1c and 30 COVID-19(-) patients with average Hb A1c were included. Hb A1c levels and parameters examined in COVID-19(+) patients were compared between groups, and correlation analysis was performed between these parameters and Hb A1c levels. The effect of Hb A1c levels on intensive care unit (ICU) admission and mortality rate in COVID-19 patients was analyzed with the χ2 test. It was observed that hemoglobin (Hb) and arterial oxygen saturation (SaO2) levels of the COVID-19 (+) groups was lower than the COVID-19 (-) group, while ferritin, D-dimer, procalcitonin (PCT), and C-reactive protein (CRP) levels were higher. The COVID-19 (+) group with high Hb A1c had higher lactate dehydrogenase (LDH), PCT and D-dimer levels than the other two groups, while Hb, partial arterial oxygen pressure (PaO2) levels were lower. The Hb A1c levels of the COVID-19 (+) groups were positively correlated with absolute neutrophil count (ANC), LDH, PCT and (K+) levels, while negatively correlated with Hb and PaO2 levels. Hb A1c was found to be associated with the inflammation process, coagulation disorders and low PaO2 in COVID-19 patients. The COVID-19 patients with high Hb A1c levels had a higher mortality rate than other COVID-19 patients. Using Hb A1c measurements with other prognostic markers would contribute to the patient's risk of death assessment.

Quantifying Worsened Glycemic Control During the COVID-19 Pandemic.

AIMS: We hypothesized that glycemic control in outpatients, measured by HbA1c, was worse during the early months of the COVID-19 pandemic than in 2019. We sought to quantify how much worse and to determine if social determinants of health were associated with these differences. MATERIALS AND METHODS: Data were extracted from the electronic medical records of 2 cohorts of patients seen in the family medicine clinic of a southeastern academic health center. Three hundred patients with baseline HbA1c results as well as HbA1c results in May 2019 or May 2020 were evaluated. RESULTS: The groups had similar mean baseline HbA1c (7.65, SD = 1.50 for 2019; 7.61, SD = 1.71 for 2020; P = .85). Mean May HbA1c decreased from baseline in 2019 (7.19, SD = 1.45) but rose in 2020 (7.63, SD = 1.73), a statistically significant difference (P < .01). Controlling for age, gender, race, and insurance status, HbA1c in May 2020 (meanadj = 7.73) was significantly higher than in May 2019 (meanadj = 7.16). CONCLUSIONS: During the early months of the COVID-19 pandemic, glycemic control in our patient population was significantly worse than during the same period in 2019 (mean HbA1c difference = 0.57). Contrary to our expectations, we did not find associations between patient demographic variables and glycemic control, including race.

The Interaction between Hb A1C and Selected Genetic Factors in the African American Population in the USA.

BACKGROUND: The global prevalence of diabetes mellitus has been growing in recent decades and the complications of longstanding type 2 diabetes continue to place a burden on healthcare systems. The hemoglobin A1c (Hb A1c) content of the blood is used to assess an individual's degree of glycemic control averaged over 2 to 3 months. In the USA, diabetes is the seventh leading cause of death. Black, indigenous, people of color (BIPOC) are disproportionately affected by diabetes compared to non-Hispanic whites. There are many reports of interaction of Hb A1c and hematologic conditions that have a high prevalence in the Black population; some of these effects are contradictory and not easily explained. This review attempts to document and categorize these apparently disparate effects and to assess any clinical impact. METHODS: Hb A1C can be determined by a variety of techniques including cation-exchange chromatography, electrophoresis, immunoassays, and affinity chromatography. The amount of Hb A1c present in a patient specimen depends not only on blood glucose but is strongly influenced by erythrocyte survival and by structural variations in the globin chains. Sickling hemoglobinopathies are well-represented in the USA in African Americans and the effects of these hemoglobin disorders as well as G6PD deficiency is examined. CONCLUSION: Hb A1c measurement should always be performed with a cautious approach. The laboratory scientist should be aware of possible pitfalls in unquestioningly determining Hb A1c without a consideration of hematologic factors, both inherited and acquired. This presents a challenge as often times, the laboratory is not aware of the patient's race.

The Effect of a Customized Nutrient-Profiling Approach on the Glycated Hemoglobin Levels of Patients With Type 2 Diabetes: Quasi-Experimental Study.

BACKGROUND: Presently, dietary management approaches are mostly oriented toward using calorie-counting and diet-tracking tools that draw our attention away from the nutritional value of our food. To improve individuals' dietary behavior, primarily that of people with type 2 diabetes, a simple technique is needed to increase their understanding of the nutritional content of their food. OBJECTIVE: This study aimed to design, develop, and evaluate a customized nutrient-profiling tool called EasyNutrition. EasyNutrition was built to introduce the new concept of nutrient profiling by applying the Intelligent Nutrition Engine, an algorithm that we developed for ranking different food recipes based on their nutritional value. This study also aimed to investigate the efficacy of EasyNutrition in lowering glycated hemoglobin (HbA1c) levels and improving dietary habits among people with type 2 diabetes. METHODS: We evaluated the utility of EasyNutrition using design science research in three sequential stages. This paper has elaborated on the third stage to investigate the efficacy of EasyNutrition in managing type 2 diabetes. A quasi-experimental study was conducted in a diabetes treatment center (n=28). The intervention group utilized EasyNutrition over 3 months, whereas participants in the control group utilized the standard of care provided by the center. Dietary habits and HbA1c levels were measured to capture any change before and after experimenting with EasyNutrition. RESULTS: The intervention group (n=9) exhibited a statistically significant change between the pre- and postexposure results of their HbA1c (t9=2.427; P=.04). Their HbA1c dropped from 8.13 to 6.72. This provided preliminary evidence of the efficacy of using a customized nutrient-profiling app in reducing HbA1c for people with type 2 diabetes. CONCLUSIONS: This study adds to the evidence base that a nutrient-profiling strategy may be a modern adjunct to diabetes dietary management. In conjunction with reliable dietary education provided by a registered dietician, EasyNutrition may have some beneficial effects to improve the dietary habits of people with type 2 diabetes.

A New α Chain Variant, Hb Heilongjiang (HBA2: c.49A>C), Found During Hb A1c Measurement.

We here report a new hemoglobin (Hb) variant found in a Chinese woman. The presence of the Hb variant can be easily recognized by HbA1c procedures based on ion exchange high performance liquid chromatography (HPLC) or capillary electrophoresis (CE) techniques. DNA sequencing revealed a new point mutation (HBA2: c.49A>C) at codon 16, resulting in an amino acid substitution from lysine to glutamine. Moreover, the Hb variant affected Hb A1c determination by VARIANT II Turbo 2.0 and D100. We named the new Hb variant Hb Heilongjiang for the birthplace of the proband.

Importance of Hemoglobin A1c Levels for the Detection of Post-Surgical Infection Following Single-Level Lumbar Posterior Fusion in Patients with Diabetes.

OBJECTIVE: Several studies have reported that patients with diabetes mellitus (DM) are vulnerable to infection. However, the mechanism underlying this remains unclear. We hypothesized that preoperative blood glucose levels in patients with DM may be a risk factor for surgical site infection (SSI). We aimed to investigate the relationship between hemoglobin A1c (HbA1c) level and SSI incidence following single-level spinal fusion surgery. METHODS: Patients with DM who underwent single-level lumbar posterior fusion surgery were retrospectively reviewed. Ninety-two patients were included and classified into the SSI and SSI-free groups. Clinical data with demographic findings were obtained and compared. The HbA1c cut-off value was defined using receiver operating characteristic (ROC) and area under the curve (AUC) analyses, which showed a significantly increased SSI risk. Potential variables were verified using multiple logistic regression analysis. RESULTS: Among the enrolled patients, 24 had SSI and 68 did not within 1 year. The preoperative HbA1c level was higher in patients with SSI (6.8%) than in the non-infected patients (6.0%; p=0.008). ROC analysis showed that if the HbA1c level is higher than 6.9%, the risk of SSI significantly increases (p=0.003; AUC, 0.708; sensitivity, 62.5%; specificity, 70.6%). The preoperative HbA1c level was significantly correlated with SSI incidence, after adjusting for potential variables (p=0.008; odds ratio, 4.500; 95% confidence interval, 1.486-13.624). CONCLUSION: The HbA1c level, indicating glycemic control, in patients with DM may be a risk factor for SSI in single-level lumbar spine posterior fusion.