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Biomedical subjects

C M Zawacki

Publications and source records attributed to C M Zawacki.

5 recordsLinked to original sources

Does microalbuminuria predict diabetic nephropathy?

OBJECTIVE: To describe risk factors associated with microalbuminuria (MA) in subjects with diabetes, investigate the predictive value of MA as a marker of risk for diabetic nephropathy (DN), and define risk factors associated with the development and progression of MA. RESEARCH DESIGN AND METHODS: We conducted a prospective longitudinal study of 23 diabetic subjects with persistent MA and 209 diabetic subjects without MA who attended diabetes clinics at the University of Michigan Medical Center in 1989 and 1990. Both groups were examined at baseline and after 7 years. At baseline, urinary albumin-to-creatinine ratios were studied in random, first morning, and 24-h urine samples. At follow-up, a 12-h overnight urine sample was collected and analyzed for albumin and creatinine. At baseline, MA was defined by at least two separate urine specimens with albumin-to-creatinine ratios between 30 and 299 microg albumin per milligram of creatinine. RESULTS: MA regressed in 56% of subjects with baseline MA without systematic application of corrective measures and developed in 16% of subjects without baseline MA. The predictive value positive of MA as a marker of risk for DN was 43%, and the predictive value negative was 77%. In the combined cohort, the incidence and progression of MA were significantly associated with poor glycemic control and duration of diabetes between 10 and 14 years. CONCLUSIONS: MA may not be as sensitive and specific a predictor of DN as previously suggested. Other markers of risk for DN are needed for optimal clinical management.

Adolescent↗

Reduced pancreatic polypeptide response to hypoglycemia and amylin response to arginine in subjects with a mutation in the HNF-4alpha/MODY1 gene.

Subjects with the Q268X mutation in the hepatocyte nuclear factor (HNF)-4alpha gene (RW pedigree/maturity-onset diabetes of the young [MODY]-1) have diminished insulin and glucagon secretory responses to arginine. To determine if pancreatic polypeptide (PP) secretion is likewise involved, we studied PP responses to insulin-induced hypoglycemia in 17 RW pedigree members: 6 nondiabetic mutation-negative [ND(-)], 4 nondiabetic mutation-positive [ND(+)], and 7 diabetic mutation-positive [D(+)]. Subjects received 0.08 U/kg body wt human regular insulin as an intravenous bolus to produce moderate self-limited hypoglycemia. PP areas under the curve (PP-AUCs) were compared among groups. With hypoglycemia, the PP-AUC was lower in the D(+) group (14,907 +/- 6,444 pg/ml, P = 0.03) and the ND(+) group (14,622 +/- 6,015 pg/ml, P = 0.04) compared with the ND(-) group (21,120 +/- 4,158 pg/ml). In addition, to determine if the beta-cell secretory defect in response to arginine involves amylin in addition to insulin secretion, we analyzed samples from 17 previously studied RW pedigree subjects. We compared the AUCs during arginine infusions for the 3 groups both at euglycemia and hyperglycemia as well as their C-peptide-to-amylin ratios. The D(+) and ND(+) groups had decreased amylin AUCs during both arginine infusions compared with the ND(-) group, but had similar C-peptide-to-amylin ratios. These results suggest that the HNF-4alpha mutation in the RW/MODY1 pedigree confers a generalized defect in islet cell function involving PP cells in addition to beta- and alpha-cells, and beta-cell impairment involving proportional deficits in insulin and amylin secretion.

Adult↗

Effect of selective screening for gestational diabetes.

OBJECTIVE: To estimate the percentage of pregnant women who would not be screened and the percentage of women with gestational diabetes mellitus (GDM) who would possibly remain undiagnosed if the American Diabetes Association's (ADA's) new selective screening recommendations are used rather than universal screening for GDM. RESEARCH DESIGN AND METHODS: Since 1987, the University of Michigan Health System has performed universal screening for GDM. In 1997, the ADA recommended that women having all four of the following characteristics need not be screened: age < 25 years, not members of an ethnic/racial group with a high prevalence of diabetes, normal body weight, and no family history of diabetes. We studied a random sample of the 25,118 deliveries at the University of Michigan between 1987 and 1997 to determine the prevalence of these four characteristics in our obstetric population. We also studied the prevalence of these four characteristics in 200 women who were diagnosed with GDM in the Endocrine Testing Unit and delivered at the University of Michigan between 1987 and 1997. RESULTS: Approximately 10-11% of women who delivered possessed all four low-risk characteristics and would not have been screened for GDM according to the new ADA recommendations. Only 4% of women (5 of 141) with GDM who delivered and for whom data on all four characteristics were reported possessed all four low-risk characteristics and would not have been screened. CONCLUSIONS: If the new ADA selective screening recommendations are used, few women with GDM will be missed (4%) but approximately 90% of pregnant women will still need to be screened for GDM.

Adult↗

Is pregnancy in diabetic women associated with folate deficiency?

OBJECTIVE: To determine whether folate metabolism in pregnant diabetic women is significantly different from that in pregnant nondiabetic women, thus predisposing them to having offspring with major congenital anomalies. RESEARCH DESIGN AND METHODS: A total of 31 pregnant diabetic women and 54 pregnant nondiabetic control subjects were studied at their first prenatal visits. Dietary folate intake, serum folate, red blood cell folate, urinary folate, and homocysteine were measured and compared after controlling for folate supplementation. Among diabetic women the relationships among parameters of folate metabolism and glycemic control were also assessed. RESULTS: There were no significant differences between the pregnant diabetic and non-diabetic women for any measures of folate metabolism after accounting for folate supplementation. In addition, among diabetic women, there were no associations among parameters of folate metabolism and glycemic control. CONCLUSIONS: Abnormal folate metabolism does not appear to occur in pregnant diabetic women. It is unlikely that deranged folate metabolism explains the higher incidence of major anomalies in infants of diabetic mothers. These results do not diminish the importance of periconception folate supplementation or preclude other possible scenarios that could restrict folate use by the embryo, leading to congenital anomalies.

Adult↗

Age effects of follicle-stimulating hormone and pulsatile luteinizing hormone secretion across the menstrual cycle of premenopausal women.

To characterize the differential aging response in gonadotropin secretion that occurs before menopause, we assessed pulsatile LH and serial FSH, estradiol (E2), and progesterone (P) concentrations in aging women across the menstrual cycle. We conducted 96 daytime studies during the follicular, midluteal, and late luteal phases of the same menstrual cycle in 32 volunteers, aged 40-50 yr (n = 16) and 19-39 yr (n = 16). Mean cycle length was shorter in the older women (26 +/- 0.4 vs. 27.6 +/- 0.6 days; P = 0.02), but mean plasma E2 and P values were similar in the two age groups. Mean plasma FSH was higher in the older group on all 3 study days. For LH, an age difference was observed during the late luteal phase, when mean plasma LH and pulse amplitude were higher in women over 40 yr of age (mean LH, 6.4 +/- 0.7 vs. 3.0 +/- 0.5 IU/L (P = 0.002); mean amplitude, 4.0 +/- 0.5 vs. 2.8 +/- 0.2 IU/L (P = 0.03)]. Pulse frequency was higher in the older group, but not different from that in younger women on all study days. When the subjects aged 35-39 yr were analyzed as a third age group (n = 8), age effects for mean LH persisted, and pulse frequency was higher in the group over 40 yr of age vs. women under age 35 yr (n = 8) in both the follicular phase (7.1 +/- 0.4 us. 5.6 +/- 0.8; P = 0.03) and late luteal phase (5.8 +/- 0.7 vs. 4.4 +/- 0.3; P = 0.03). Although highly variable, individual patterns of gonadotropin secretion in the women over age 40 yr included a sustained elevation in the FSH/LH ratio as well as a failure to demonstrate slow frequency, high amplitude LH pulses in the midluteal phase. In conclusion, 1) the age-related increase in FSH concentrations in ovulatory women, although more pronounced, is associated with phase-dependent enhancement of pulsatile LH secretion; 2) the higher LH concentrations are brought about by changes in both pulse frequency and amplitude; and 3) these age effects preempt overt reductions in cyclic E2 or P concentrations.

Adolescent↗