Glycemic control: Risk factors, quality of life, workforce participation, and mortality among US adults with type 2 diabetes

Despite research showing the benefits of glycemic control, it remains suboptimal among adults with diabetes in the United States. Possible reasons include unaddressed risk factors as well as lack of awareness of its immediate and long term consequences. The objectives of this study were to, using cross-sectional data, (1) ascertain the association between suboptimal (Hemoglobin A1c (HbA1c) .7%), borderline (HbA1c 7-8.9%), and poor (HbA1c .9%) glycemic control and potentially new risk factors (e.g. work characteristics), and (2) assess whether aspects of poor health and well-being such as poor health related quality of life (HRQOL), unemployment, and missed-work are associated with glycemic control; and (3) using prospective data, assess the relationship between mortality risk and glycemic control in US adults with type 2 diabetes. Data from the 1988-1994 and 1999-2004 National Health and Nutrition Examination Surveys were used. HbA1c values were used to create dichotomous glycemic control indicators. Binary logistic regression models were used to assess relationships between risk factors, employment status and glycemic control. Multinomial logistic regression analyses were conducted to assess relationships between glycemic control and HRQOL variables. Zero-inflated Poisson regression models were used to assess relationships between missed work days and glycemic control. Cox-proportional hazard models were used to assess effects of glycemic control on mortality risk. Using STATA software, analyses were weighted to account for complex survey design and non-response. Multivariable models adjusted for socio-demographics, body mass index, among other variables. Results revealed that being a farm worker and working over 40 hours/week were risk factors for suboptimal glycemic control. Having greater days of poor mental was associated with suboptimal, borderline, and poor glycemic control. Having greater days of inactivity was associated with poor glycemic control while having greater days of poor physical health was associated with borderline glycemic control. There were no statistically significant relationships between glycemic control, self-reported general health, employment, and missed work. Finally, having an HbA1c value less than 6.5% was protective against mortality. The findings suggest that work-related factors are important in a person’s ability to reach optimal diabetes management levels. Poor glycemic control appears to have significant detrimental effects on HRQOL.^

Biomimetic modeling of the nitrogen-centered radical postulated to occur during the inhibition of ribonucleotide reductases by 2'-azido-2'-deoxynucleotides

Ribonucleotide reductases (RNR) are essential enzymes that catalyze the reduction of ribonucleotides to 2'-deoxyribonucleotides, which is a critical step that produces precursors for DNA replication and repair. The inactivation of RNR, logically, would discontinue producing the precursors of the DNA of viral or cancer cells, which then would consequently end the cycle of DNA replication. Among different compounds that were found to be inhibitors of RNR, 2'-azido-2'-deoxynucleotide diphosphates (N3NDPs) have been investigated in depth as potent inhibitors of RNR. Decades of investigation has suggested that the inactivation of RNR by N3NDPs is a result of the formation of a nitrogen-centered radical (N·) that is covalently attached to the nucleotide at C3' and cysteine molecule C225 [3'-C(R-S-N·-C-OH)]. Biomimetic simulation reactions for the generation of the nitrogen-centered radicals similar to the one observed during the inactivation of the RNR by azionuclotides was investigated. The study included several modes: (i) theoretical calculation that showed the feasibility of the ring closure reaction between thiyl radicals and azido group; (ii) synthesis of the model azido nucleosides with a linker attached to C3' or C5' having a thiol or vicinal dithiol functionality; (iii) generation of the thiyl radical under both physiological and radiolysis conditions whose role is important in the initiation on RNR cascades; and (iv) analysis of the nitrogen-centered radical species formed during interaction between the thiyl radical and azido group by electron paramagnetic resonance spectroscopy (EPR). Characterization of the aminyl radical species formed during one electron attachment to the azido group of 2'-azido-2'-deoxyuridine and its stereospecifically labelled 1'-, 2'-, 3'-, 4'- or 5,6-[2H 2]-analogues was also examined. This dissertation gave insight toward understanding the mechanism of the formation of the nitrogen-centered radical during the inactivation of RNRs by azidonucleotides as well as the mechanism of action of RNRs that might provide key information necessary for the development of the next generation of antiviral and anticancer drugs.

Glycemic Control: Risk Factors, Quality of Life, Workforce Participation, and Mortality Among US Adults with Type 2 Diabetes

Despite research showing the benefits of glycemic control, it remains suboptimal among adults with diabetes in the United States. Possible reasons include unaddressed risk factors as well as lack of awareness of its immediate and long term consequences. The objectives of this study were to, using cross-sectional data, 1) ascertain the association between suboptimal (Hemoglobin A1c (HbA1c) ≥7%), borderline (HbA1c 7-8.9%), and poor (HbA1c ≥9%) glycemic control and potentially new risk factors (e.g. work characteristics), and 2) assess whether aspects of poor health and well-being such as poor health related quality of life (HRQOL), unemployment, and missed-work are associated with glycemic control; and 3) using prospective data, assess the relationship between mortality risk and glycemic control in US adults with type 2 diabetes. Data from the 1988-1994 and 1999-2004 National Health and Nutrition Examination Surveys were used. HbA1c values were used to create dichotomous glycemic control indicators. Binary logistic regression models were used to assess relationships between risk factors, employment status and glycemic control. Multinomial logistic regression analyses were conducted to assess relationships between glycemic control and HRQOL variables. Zero-inflated Poisson regression models were used to assess relationships between missed work days and glycemic control. Cox-proportional hazard models were used to assess effects of glycemic control on mortality risk. Using STATA software, analyses were weighted to account for complex survey design and non-response. Multivariable models adjusted for socio-demographics, body mass index, among other variables. Results revealed that being a farm worker and working over 40 hours/week were risk factors for suboptimal glycemic control. Having greater days of poor mental was associated with suboptimal, borderline, and poor glycemic control. Having greater days of inactivity was associated with poor glycemic control while having greater days of poor physical health was associated with borderline glycemic control. There were no statistically significant relationships between glycemic control, self-reported general health, employment, and missed work. Finally, having an HbA1c value less than 6.5% was protective against mortality. The findings suggest that work-related factors are important in a person’s ability to reach optimal diabetes management levels. Poor glycemic control appears to have significant detrimental effects on HRQOL.