Kay F. McFarland

Nonenzymatic Glucosylation of Serum Proteins in Diabetes Mellitus

The extent of nonenzymatic glucosylation of serum protein in control and diabetic subjects was measured by a chemical procedure using thiobarbituric acid. A mean value of 0.81 (±0.21 SD) nmol glucose per milligram serum protein was observed in the control group. Diabetics displayed elevated levels of glucosylated serum proteins, up to 4 nmol glucose per milligram protein. Glucosylation of serum protein correlated strongly with fasting blood sugar (r = 0.71), percent hemoglobin A1 (r = 0.79), and percent glucosylated albumin (r = 0.99). There was no overlap between control and diabetic groups, i.e., within 3 SD of the mean of controls. These studies indicate that the assay for glucosylated serum protein appears to be an especially sensitive indicator of the degree of hyperglycemia in diabetes.

Risk factors and noncontraceptive estrogen use in women with and without coronary disease

To evaluate the risk factors for coronary disease, 345 women, aged 35 to 59 years, who had undergone coronary arteriography for suspected coronary disease completed a mail questionnaire, telephone interview, or both. Two hundred eight women with angiographically normal coronary arteries constituted the control group, and 137 with a 70% or more occlusion of one or more coronary vessels were classified as having severe coronary occlusive disease. Age-adjusted odds of severe coronary disease based on the logistic regression model for the risk factors evaluated were as follows: smoking, 5.73 (p less than 0.001); diabetes, 5.09 (p less than 0.001); cholesterol level greater than 240 mg/dl, 2.35 (p less than 0.05); a parental history of death from heart disease before age 60 years, 2.03 (p less than 0.05); and estrogen use for 6 months or longer, 0.50 (p less than 0.01). There were no differences with regard to the presence of obesity and a history of hypertension in women with and without coronary disease. These data support the hypothesis that use of noncontraceptive estrogen significantly reduces the risk of severe coronary disease, whereas smoking, an elevated cholesterol level, and a parental history of heart disease all increase the risk of ischemic heart disease in women.

Effect of diabetes and aging on carboxymethyllysine levels in human urine

Carboxymethyllysine (CML) has been identified as a modified amino acid that accumulates with age in human lens proteins and collagen. CML may be formed by oxidation of fructoselysine (FL), the Amadori adduct formed on nonenzymatic glycosylation of lysine residues in protein, or by reaction of ascorbate with protein under autoxidizing conditions. We proposed that measurements of tissue and urinary CML may be useful as indices of oxidative stress or damage to proteins in vivo. To determine the extent to which oxidation of nonenzymatically glycosylated proteins contributes to urinary CML, we measured the urinary concentrations of FL and CML in diabetic (n = 26) and control (n = 28) patients. The urinary concentration of FL correlated strongly with HbA1 measurements and was significantly higher in diabetic compared with control samples (9.2 ± 6.5 and 4.0 ± 2.8 μg/mg creatinine, respectively; P < 0.0001). There was also a strong correlation between the concentrations of CML and FL in both diabetic and control urine (r = 0.67, P < 0.0001) but only a weakly significant increase in the CML concentration in diabetic compared with control urine (1.2 ± 0.5 and 1.0 ± 0.3 μg/mg creatinine, respectively; P = 0.05). The molar ratio of CML to FL was significantly lower in diabetic compared with control patients (0.25 ± 0.12 and 0.43 ± 0.16, respectively; P < 0.0001). The correlation between urinary FL and CML and the increase in CML in diabetic urine suggests that urinary CML is derived in part from autoxidation of FL in nonenzymatically glycosylated proteins, whereas the decreased ratio of CML to FL in diabetic urine suggests that oxidative stress is decreased in diabetes. The ratio of CML to FL showed no correlation with age in either diabetic or control populations, arguing against an increase in oxidative stress to proteins with age.

Changes in Blood Protein Glycosylation During a Diabetes Summer Camp

To evaluate changes in glycemic control during a 2-wk diabetes summer camp program, fasting plasma glucose (FPG), glycosylated hemoglobin (GHb), and glycosylated serum protein (GSP) levels were measured in a group of 36 children at the beginning and end of camp. Average FPG and GHb were unchanged during the 2-wk period, but the average decrease in GSP (7%) was significant (P < 0.005). The results of this study indicate that a measurable improvement in diabetic control occurred in some children during the 2-wk summer camp program.

Measurement of Nonenzymatically Glucosylated Serum Protein by an Improved Thiobarbituric Acid Assay

We describe here some useful modifications of the thiobarbituric acid (TBA) assay for measurement of nonenzymatic glucosylation of serum protein. The modified assay minimizes interference by glucose without a lengthy dialysis step, and does not require an independent blank determination. These modifications should make the TBA assay more convenient for evaluating glycemic control in diabetes. Serum protein is first precipitated with cold ethanol to remove endogenous glucose. The protein is then hydrolyzed in an oxalic acid solution to release glucose as hydroxymethylfurfural (HMF). The HMF is reacted with TBA to form a chromophore which is extracted into isobutanol for spectrophotometric analysis (lambda max = 435 nm). The absorbance at 435 nm is corrected by subtracting a blank reading at 500 nm, and the nmol HMF released is determined using a standard curve prepared with pure HMF. Normal values of this assay for both adults and children are 0.38 +/- 0.10 nmol HMF/mg serum protein (means +/- 2 SD). When the assay was applied to serum samples from a group of 39 Type I diabetic children more than 90% of the children exceeded the normal range of the assay.

Purpose in life and self-actualization in agency-supported caregivers.

When families cannot serve as full-time caregivers for severely, mentally ill family members, agency-supported caregivers provide an alternative to chronic hospitalization. Caregivers who provide 24 hour per day care experience caregiver burden; they also find rewards and meaning in their work. The purpose of this study is to observe positive experiences of paid caregivers for seriously, mentally ill individuals, especially the meaning or purpose it gives their lives and the self-fulfilment or self-actualization that caregiving provides. The caregivers in this study possessed a high purpose in life suggesting that caregiving may give meaning to life. Also, the caregivers of these individuals with severe, mental illness tend to be highly other-oriented (altruistic), an external focus that may decrease their own self-awareness. Thus, caregivers who provide continuous residential care may benefit from therapeutic interventions designed to reinforce self-care skills.

The Relationship of Maternal Age on Gestational Diabetes

This study was performed to examine the relationship between maternal age and serum glucose levels during pregnancy, and to determine if glucose screening could be eliminated in very young women without significantly compromising the detection rate of gestational diabetes mellitus. All women between the 24th and 28th wk of gestation who were followed in a university-affiliated prenatal clinic had a screening glucose level drawn 1 h after ingesting 50 g glucose. Those who had a 1-h serum glucose of > 150 mg/dl subsequently underwent a 3-h glucose tolerance test. There was a progressive increase in screening serum glucose levels and a significantly higher incidence of diabetes with increasing maternal age. Only 4% of women < 20 yr had a positive screen and 8% of these had gestational diabetes. If screening had not been done in those < 20 yr, only 5% (2/36) of women with gestational diabetes would not have been detected.

Gender-Related Values and Medical Specialty Choice

During orientation, all 74 first-year medical students at the University of South Carolina responded to a survey about their preferences regarding specialty, work hours, leisure-time activities, and the quality they most valued in their own physician. More women than men listed a primary care specialty as their specialty choice. The men indicated a desire to work longer hours than the women, whereas a greater proportion of the women than men chose to spend their leisure time with family and friends. This study suggests that these gender-related values may influence practice choices.

Neonatal Mortality in Infants of Diabetic Mothers

To assess the effects of an educational program emphasizing detection and tight control of maternal glucose levels during pregnancy, the management and outcome of all pregnancies complicated by diabetes mellitus delivered at a county hospital during two time periods, 1978–1980 and 1981–1983, are compared. The prevalence of diabetes during pregnancy was 1.4% between 1978 and 1980 and 2.6% between 1981 and 1983 (P < 0.01). The perinatal death rate decreased for infants of diabetic mothers from 100 per thousand deliveries in 1978–1980 to 32 per thousand in 1981–1983 (P < 0.02). The perinatal death rate for infants of mothers with gestational diabetes was nearly the same as the perinatal death rate for all neonates born in the state in 1981–1983. Congenital anomalies followed by stillbirths were the most frequent causes of perinatal death.