The impact of glucose tolerance state on seropositivity rate after hepatitis B vaccination.

Immunization is recommended for people with diabetes mellitus (DM), but little information is available on their seropositivity rates. To determine the impact of glucose tolerance state on seropositivity rate after hepatitis B vaccination, we included 7645 adult participants from the National Health and Nutrition Examination Survey 2005-2016 who reported three doses of hepatitis B vaccine and were seropositive for anti-hepatitis B surface antibody (≥ 12.0 mIU/mL), after exclusion of those positive for anti-hepatitis B core antibody and/or hepatitis B surface antigen. We classified the states of glucose tolerance as normal glucose tolerance (NGT, 61.68%), abnormal glucose tolerance (AGT, 26.02%), or DM (13.30%). We observed a stepwise decline in hepatitis B seropositivity rate from NGT (53.64%) to AGT (45.52%) to DM (28.84%) (P < 0.0001). We confirmed these results after standardization for age and BMI (P < 0.0001 for all subgroup analyses) and in subgroup analyses by gender and racial/ethnic group. Dysregulated glucose metabolism is associated with a decreased seropositivity rate after hepatitis B vaccination. Our observations suggest that regular follow-up screening for anti-hepatitis B surface antibody, with additional booster vaccination as necessary, is especially important in patients with DM. Whether a similar phenomenon exits for other vaccines, especially COVID-19, remains to be investigated.

Role of hepatitis A virus in diabetes mellitus.

BACKGROUND: Although much information is available regarding hepatitis C virus infection and diabetes, less is known about the relationship between hepatitis A virus (HAV) infection and diabetes. AIM: To examine the roles of HAV in diabetes risk. METHODS: This cross-sectional study population included data from the National Health and Nutrition Examination Survey collected between 2005-2012. Adult subjects (≥ 20 years old) with available body mass index measurements, defined diabetes status, history of HAV vaccination, and HAV serology were included. HAV vaccination was based on self-reported history. Successful HAV immunization was defined as the presence of both vaccination and anti-HAV antibody. HAV infection was defined by the absence of vaccination but presence of anti-hepatitis A antibody. The odds ratio (OR) for diabetes with 95% confidence intervals (95%CI) was calculated for each HAV status and then adjusted for covariates. Sensitivity tests, based on different definitions of diabetes, were performed to verify the results. RESULTS: Among 19942 subjects, 4229 subjects (21.21%) received HAV vaccination and HAV antibody was present in 9224 subjects (46.25%). Although HAV infection was associated with an increased risk of diabetes (OR: 1.13; 95%CI: 1.08-1.18), HAV vaccination was not associated with diabetes (OR: 1.06; 95%CI: 0.95-1.18), and successful HAV immunization had no impact on the risk of diabetes (OR: 1.11; 95%CI: 0.97-1.27). Thus, HAV infection was an unlikely cause of diabetes. Alternatively, in non-vaccinated subjects, diabetes increased the risk of HAV infection by 40% (OR: 1.40, 95%CI: 1.27-1.54). CONCLUSION: An association between HAV infection and diabetes is observed which is best explained by an increased risk of HAV infection in diabetic patients. Diabetic subjects are more susceptible to HAV. Thus, HAV vaccination is highly recommended in diabetic patients.

The Role of Hemoglobin A1C in Diabetes Screening and Diabetic Retinopathy.

Hemoglobin A1C (A1C) is used in various settings. Its performance has not been evaluated systemically. We compared A1C in diagnosis of diabetes with fasting plasma glucose (FPG) and 2-h postchallenged plasma glucose (2hPG) parameters in a cross-sectional cohort in the United Stated. Adult subjects (≥20 years) were identified from the National Health and Nutrition Examination Survey 2005-2016 without a history of diabetes who had BMI, A1C, FPG, and 2hPG (n = 10,416). For comparisons, we calculated the sample weighted prevalence, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with subgroup analyses. For the retinopathy study, diabetic subjects with established diabetes who responded to the question of diabetic retinopathy were evaluated (n = 3907). Compared to the FPG/2hPG criteria, A1C ≥ 48 mmol/mol (6.5%) had a low sensitivity at 25.90%, with specificity 99.70%, PPV 84.70%, and NPV 95.70%. Subgroup analyses revealed a lower sensitivity in males (24.52%); the lowest in non-Hispanic White (21.35%), in the third decade (14.32%), and in the BMI < 22.50 kg/m2 group (7.21%). The prevalence of self-reported diabetic retinopathy increased drastically with an inflection point at A1C 48 mmol/mol (6.5%) from 11.52% to 18.32% (p < 0.0001). A1C ≥ 48 mmol/mol (6.5%) should be cautiously used to diagnose diabetes in certain subgroups due to very low sensitivity in certain groups. With the confirmation of the association of increasing self-reported diabetic retinopathy with A1C ≥ 48 mmol/mol (6.5%), the current A1C cutoff is an acceptable value with the understanding of especially low sensitivity in certain subgroups.

Daily Intake and Serum Levels of Copper, Selenium and Zinc According to Glucose Metabolism: Cross-Sectional and Comparative Study.

Trace elements play an important role in metabolism. We compared the daily intake and serum concentrations of copper (Cu), selenium (Se), and zinc (Zn) across a spectrum of glucose tolerance status in a representative U.S. population. Daily intake and serum concentrations of Cu, Zn and Se in 5087 adults from the 2011-2016 National Health and Nutrition Examination Survey (NHANES) were examined and compared to normal (NGT) and abnormal (AGT) glucose tolerance and the presence of diabetes mellitus (DM). Other than Zn deficiency (21.15%), the prevalence of Zn, Se, and Cu excess and Se and Cu deficiency were low (<4.00%). As compared to the NGT group, Cu and Se supplementation was higher in the AGT and DM groups (p < 0.0001 for all). Serum Se and Zn, but not Cu, concentrations were highly correlated with daily intake (p < 0.0001 for both). As compared to the NGT group, serum Cu concentration was highest in the AGT group (p = 0.03), serum Se concentration was highest in the DM group (p < 0.0001), and serum Zn concentration was highest in the AGT group (p < 0.0001). Serum Se and Zn concentration was correlated with daily Se and Zn intake. Even within the reference range for serum Cu, Se, and Zn concentrations, a higher serum concentration of Cu, Se, and Zn was associated with abnormal glucose metabolism. Although the casual relationship remains to be elucidated, these data suggest caution in Cu, Se and Zn supplementation in non-deficient individuals.

Conundrum of vitamin D on glucose and fuel homeostasis.

As an endocrine hormone, vitamin D plays an important role in bone health and calcium homeostasis. Over the past two decades, the non-calcemic effects of vitamin D were extensively examined. Although the effect of vitamin D on beta cell function were known for some time, the effect of vitamin D on glucose and fuel homeostasis has attracted new interest among researchers. Yet, to date, studies remain inconclusive and controversial, in part, due to a lack of understanding of the threshold effects of vitamin D. In this review, a critical examination of interventional trials of vitamin D in prevention of diabetes is provided. Like use of vitamin D for bone loss, the benefits of vitamin D supplementation in diabetes prevention were observed in vitamin D-deficient subjects with serum 25-hydroxyvitamin D < 50 nmol/L (20 ng/mL). The beneficial effect from vitamin D supplementation was not apparent in subjects with serum 25-hydroxyvitamin D > 75 nmol/L (30 ng/mL). Furthermore, no benefit was noted in subjects that achieved serum 25-hydroxyvitamin D > 100 nmol/L (40 ng/mL). Further studies are required to confirm these observations.

Hypovitaminosis D is Associated with Psoriasis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Psoriasis is a chronic inflammatory and immune-mediated skin disease that affects over 7.2 million U.S. adults. Current treatment has improved clinical outcomes. Vitamin D is believed to affect the proliferation and regeneration of keratinocytes; therefore, its deficiency is a possible risk factor; however, there is still no definite evidence. The objective of this study was to synthesize existing data on the relationship between hypovitaminosis D and psoriasis. METHODS: A meta-analysis of relevant studies was conducted by doing a comprehensive search in the MEDLINE, EMBASE, and the Cochrane Central Register through July 2018 to identify relevant cohort studies and to assess serum 25-hydroxyvitamin D (25(OH)D) levels in adults with psoriasis. The primary outcome was the mean difference in serum 25(OH)D level between psoriatic patients and controls. RESULTS: The initial search identified 107 articles. Only ten studies met the criteria for full-paper review. Meta-analysis was conducted from ten prospective cohort studies involving 6,217 controls and 693 cases. The pooled mean difference in serum 25(OH)D level between psoriatic patients and controls was -6.13 ng/ml (95% CI, -10.93 to -1.32, p-value = 0.01). The between-study heterogeneity (I2) was 98%, p < 0.00001. CONCLUSION: Our meta-analysis was the first study to establish the relation between vitamin D and psoriasis. The result found a significant relationship between low 25(OH) D levels and psoriasis, but did not establish a causal relationship. Further studies will be required to establish whether vitamin D supplementation benefits patients with psoriasis.

PROGNOSIS OF DIFFERENTIATED THYROID CARCINOMA IN PATIENTS WITH GRAVES DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Objective: It is still controversial whether differentiated thyroid carcinoma (DTC) in patients with Graves disease (GD) can be more aggressive than non-Graves DTC. We conducted a systematic review and meta-analysis to examine the association between GD and prognosis in patients with DTC. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2019. We included published studies that compared the risk of mortality and prognosis between DTC patients with GD and those with non-GD. Data from each study were combined using the random-effects model. Results: Twenty-five studies from February 1988 to May 2018 were included (987 DTC patients with GD and 2,064 non-Graves DTC patients). The DTC patients with GD had a significantly higher risk of associated multifocality/multicentricity (odds ratio, 1.45; 95% confidence interval, 1.04 to 2.02; I2, 6.5%; P = .381) and distant metastasis at the time of cancer diagnosis (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; I2, 0.0%; P = .497), but this was not associated with DTC-related mortality and recurrence/persistence during follow-up. Conclusion: Our meta-analysis demonstrates a statistically significant increased risk of multifocality/multicentricity and distant metastasis at the time of cancer diagnosis in DTC patients with GD than those without GD. Abbreviations: CI = confidence interval; DTC = differentiated thyroid carcinoma; GD = Graves disease; LN = lymph node; OR = odds ratio; PTC = papillary thyroid carcinoma; TC = thyroid carcinoma; TSAb = thyroid-stimulating antibody; TSH = thyroid-stimulating hormone.

Adherence to Guideline Recommendations in Patients with Thyroid Nodules.

INTRODUCTION: Thyroid nodules are common and fine-needle aspiration (FNA) biopsy is the standard of care for work-up to exclude thyroid cancer. In this study, we examined the discrepancy between daily practice and recommended diagnostic approach for management of thyroid nodules, based on history taking, laboratory, and imaging studies. METHODS: This was a retrospective chart review of 199 patients who had ultrasound-guided fine needle aspiration (UGFNA) performed at a Midwest academic medical center from January 2010 to December 2011. The quality measures were selected based on recommended clinical practice guidelines, including family history, history of neck radiation, neck symptoms, TSH test, and thyroid ultrasound. RESULTS: The majority of patients were Caucasian females. Family history of thyroid cancer and childhood neck radiation exposure were documented in 79 subjects (40%) and 76 subjects (38%), respectively. Neck symptoms were documented in most subjects, including dysphonia (56.8%), dysphagia (69.9%), and dyspnea (41.2%). Most subjects had a TSH measured and an ultrasound performed prior to biopsy (75% and 86%, respectively). CONCLUSIONS: It appears there is a gap between current patient care and clinical practice guidelines for management of thyroid nodules. Clinical history and ultrasound features for risk stratification of UGFNA were lacking, which could reflect physicians' unfamiliarity with the guidelines. As thyroid nodules are common, enhancing knowledge of the current guidelines could improve appropriate work-up. Further studies are needed to identify factors associated with the poor compliance with clinical guidelines in management of thyroid nodules.

Viral Hepatitis and Diabetes: Clinical Implications of Diabetes Prevention Through Hepatitis Vaccination.

Viral hepatitis has been posited to play a role in the development of type 2 diabetes. Thus, prevention of viral hepatitis through vaccination has the potential to reduce the burden of type 2 diabetes. We have shown that successful hepatitis B vaccination reduces the risk of diabetes by 33 %. Although diabetes can be prevented by behavior modification and pharmaceutical agents, these require significant personal commitment and cost. In contrast, diabetes prevention through hepatitis B vaccination would require little personal commitment and relatively low cost. In this review, we discuss hepatitis viruses A, B, and C and their interaction with diabetes; explore the potential underlying mechanisms and potential for hepatitis vaccination to reduce diabetes; and estimate the medical expense savings that would result from such an intervention. Given the projected increase of diabetes prevalence in the developing regions, where hepatitis B is endemic, exploration of such an intervention is very timely.

Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration.

To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m(2), P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained.

Association of insulin resistance with serum ferritin and aminotransferases-iron hypothesis.

AIM: To investigate the relationship of iron indices with diabetes mellitus (DM) in those without hemochromatosis. METHODS: This cross-sectional study examined data collected during the Third National Health and Nutrition Examination Survey (NHANES III). Only those who fasted properly and were not anemic with transferrin saturation < 45% were included (n = 6849). Insulin sensitivity and beta cell function were calculated from fasting glucose and insulin concentrations. Indices of iron metabolism were examined in the presence or absence of DM. We examined the relationship of insulin sensitivity and beta cell function with serum ferritin concentration. The influence of C-reactive protein and liver enzymes was also investigated. RESULTS: Serum ferritin concentration was significantly higher in diabetic subjects (P = 0.0001 to < 0.000001). The difference remained significant after adjustment for age, body mass index, alcohol consumption, and mineral/iron supplement (P = 0.03 to < 0.000001). In those who did not take insulin, serum ferritin concentration was negatively associated with insulin sensitivity (P = 0.05 to 0.00001), but not with beta cell function. The alanine aminotransferase was correlated with serum ferritin concentration (P = 0.02 to < 0.000001) but not with insulin sensitivity, suggesting the role of the liver in iron-associated insulin resistance. CONCLUSION: As most of diabetes is type 2 diabetes and insulin resistance is a cardinal feature of type 2 diabetes, disordered iron metabolism could play a role in the pathogenesis of insulin resistance and type 2 diabetes through its effect on liver function.

The Impact of Hepatitis B Vaccination Status on the Risk of Diabetes, Implicating Diabetes Risk Reduction by Successful Vaccination.

BACKGROUND: The liver plays a key role in fuel metabolism. It is well established that liver disease is associated with an increased risk for diabetes mellitus. Hepatitis C virus infection has been known to increase the risk of diabetes. However, much less is known about the role of hepatitis B virus (HBV) infection in diabetes. We examined the association of diabetes based on the vaccination status for HBV. METHODS: In this cross-sectional study, we included adult subjects (≥20 y/o) with HBV serology available from the National Health and Nutrition Examination Survey 2005-2010. Diabetes was defined as established diabetes or fasting plasma glucose concentration ≥7.0 mmol/L, 2-hour plasma glucose concentration ≥11.1 mmol/L, or HbA1c ≥ 47.5 mmol/mol (6.5%). Vaccination was based on the reported history and immunization was determined by HBV serology. The odds ratio (OR) with 95% confidence intervals (95% CI) were calculated with consideration of the following covariates: age, gender, BMI, ethnic/racial group, current smoker, current alcohol consumption, family history of diabetes, poverty index, and education. RESULTS: This study included 15,316 subjects. Among them, 2,320 subjects was immunized based the HBV serology. Among 4,063 subjects who received HBV vaccination, successful vaccination was only noted in 39% of subjects. The HBV vaccination was not associated with diabetes (OR: 1.08, 95%CI: 0.96-1.23). Serology evidence of HBV immunization was associated with a reduced OR of diabetes (0.75, 95%CI: 0.62-0.90). Successful HBV vaccination was also associated with a reduced OR of diabetes (0.67, 95%CI: 0.52-0.84). CONCLUSIONS: Although our study shows the association of HBV vaccination with the reduced odds of diabetes by 33%, a prospective study is warranted to confirm and examine the impact of HBV vaccination in prevention of diabetes.

Clinical implication of fasting and post-challenged plasma glucose in diagnosis of diabetes mellitus.

Fasting plasma glucose (FPG) is the preferred test in diagnosis of diabetes mellitus (DM) to 2-h post-challenged plasma glucose (2hPG). There is little information available on the comparison between FPG and 2hPG diagnostic criteria. This study included adult participants (≥18 years old) of the NHANES 2005-2010 with FPG, 2hPG, and BMI measured. Subjects with established DM were excluded. The sensitivity of FPG and 2hPG diagnostic criteria was compared as the main outcome measure. Among 5,782 subjects, 476 subjects (8.23 %) were diagnosed with DM by either FPG, 2hPG, or both criteria. Among the subjects meeting the criterion of FPG, those with 2hPG <200 mg/dL were younger (57 ± 16 vs. 61 ± 15 years old, P < 0.05, mean ± STD) and less obese (30.81 ± 7.89 vs. 32.71 ± 6.68 kg/m(2), P < 0.05) as compared to those with 2hPG ≥200 mg/dL. Among the subjects meeting the criterion of 2hPG, those with FPG <126 mg/dL were more female (55.41 vs. 39.88 %, P < 0.0002), less obese (29.24 ± 5.83 vs. 32.71 ± 6.68 kg/m(2), P < 0.000001), lower diastolic blood pressure (67 ± 12 vs. 71 ± 14 mmHg, P < 0.02), and less family history of DM (36.35 vs. 48.47 %, P < 0.02) as compared to those with FPG ≥126 mg/dL. The sensitivity of diagnosis of DM was only 41.37 % for FPG criterion, while it was 66.53 % for 2hPG criterion. Thus, compared to 2hPG criterion, FPG criterion had a lower sensitivity detecting new cases of DM. The use of FPG criterion would more likely result in underdiagnosing DM, especially in female and less obese subjects, as compared to the use of 2hPG criterion.