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Biomedical subjects

Lois Jovanovic

Publications and source records attributed to Lois Jovanovic.

At least 19 recordsLinked to original sources
PubMed2006

Reduction in hematocrit level after pioglitazone treatment is correlated with decreased plasma free testosterone level, not hemodilution, in women with polycystic ovary syndrome.

Thiazolidinediones have gained widespread use for the treatment of type 2 diabetes mellitus and other insulin resistance states, including polycystic ovary syndrome (PCOS). In thiazolidinedione-treated patients a small reduction in hemoglobin and hematocrit levels often is observed, and this generally has been attributed to fluid retention. Because testosterone is a hematopoietic hormone, we investigated whether a reduction in plasma free testosterone concentration was associated with the decrease in hemoglobin and hematocrit levels in 22 nondiabetic women (9 with normal glucose tolerance and 13 with impaired glucose tolerance; mean age, 29 +/- 5 years; mean body mass index, 35.6 +/- 5.8 kg/m2) with PCOS who were treated with pioglitazone, 45 mg/d. Before treatment and after 4 months, subjects underwent an oral glucose tolerance test and measurement of total body water content with bioimpedance. Plasma testosterone, androstenedione, dehydroepiandrosterone sulfate, hemoglobin, and hematocrit levels were evaluated at baseline and every month for 4 months. The fasting plasma glucose concentration (98 +/- 9 mg/dL) was unchanged after pioglitazone treatment, whereas the 2-hour plasma glucose concentration declined from 146 +/- 41 to 119 +/- 20 mg/dL (P = .002). Both the free androgen index and the free testosterone levels calculated according to Vermeulen et al decreased significantly (from 14.4 +/- 7.1 to 10.6 +/- 7.8 [P = .02] and from 59.4 +/- 23.4 to 46.6 +/- 23.3 [P = .03], respectively). The plasma androstenedione level declined from 259 +/- 134 to 190 +/- 109 ng/dL (P = .01), whereas the dehydroepiandrosterone sulfate level did not change significantly (from 139 +/- 90 to 127 +/- 84 mug/dL, P = .2 [not significant]). The levels of both hemoglobin (from 13.6 +/- 1.0 to 12.8 +/- 1.1 g/dL, P = .0002) and hematocrit (from 39.7% +/- 2.2% to 37.9% +/- 2.7%, P = .002) fell slightly after 4 months of pioglitazone administration. Collectively, before and after pioglitazone administration, the plasma free testosterone level according to Vermeulen et al correlated positively with the levels of hemoglobin (r = 0.49, P < .0001) and hematocrit (r = 0.40, P < .0001), as well as the free androgen index (r = 0.38 [P < .0003] with hemoglobin and r = 0.29 [P < .006] with hematocrit); the decrement in plasma free testosterone level and free androgen index also correlated with the decrements in the levels of both hemoglobin (r = 0.51 [P = .01] and r = 0.54 [P = .01], respectively) and hematocrit (r = 0.42 [P = .05] and r = 0.50 [P = .02], respectively). Body weight increased from 90.5 +/- 17.3 to 92.4 +/- 18.8 kg after pioglitazone administration (P = .05), as did body fat content (from 42.7 +/- 15.3 to 44.8 +/- 17.1 kg, P = .03), which could explain the increase in weight, because edema did not develop in any of the subjects. Total body water content did not change significantly after pioglitazone administration (from 37.7 +/- 5.0 to 37.8 +/- 4.9 L, P = .68 [not significant]). In summary, pioglitazone treatment is associated with a mild decline in hematocrit or hemoglobin level, which is correlated with the reduction in plasma testosterone level. These results suggest that increased body water content cannot explain the reduction in hematocrit or hemoglobin level in women with PCOS. Further studies are necessary to evaluate whether the same scenario is applicable to normoandrogenic women and individuals with type 2 diabetes mellitus.

Adult↗
PubMed2006

Targeting postprandial hyperglycemia.

In healthy individuals, blood glucose levels in the fasting state are maintained by the continuous basal-level insulin secretion. After a meal, the rise in postprandial glucose (PPG) is controlled by the rapid pancreatic release of insulin, stimulated by both glucose and the intestinal production of the incretins glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1. In diabetic individuals, postprandial insulin secretion is insufficient to suppress an excessive rise in PPG. There is increasing evidence that elevated PPG exerts a more deleterious effect on the vascular system than elevation of fasting plasma glucose. In particular, individuals with normal fasting plasma glucose but impaired glucose tolerance have significantly increased risk of cardiovascular events. With the recognition of the importance of PPG and the availability of new pharmacologic options, management of diabetes will shift to greater attention to PPG levels. The prototype for such an approach is in the treatment of gestational diabetes and diabetic pregnancies where PPG is the primary target of efforts at glycemic control. These efforts have been extremely successful in improving the outlook for diabetic pregnant women. There are many approaches to reduction of PPG; dietary management and promotion of exercise are very effective. Sulfonylureas, meglitinides, metformin, thiazolidinediones, and disaccharidase inhibitors all counteract PPG elevation. The development of glucagon-like peptide 1 agonists such as exendin and dipeptidyl peptidase IV inhibitors such as vildagliptin offers a new approach to suppression of PPG elevation. New semisynthetic insulin analogues permit a more aggressive response to postprandial glucose elevation, with lower risk of hypoglycemia, than with regular insulin. Inhaled insulin also has a rapid onset of action and offers benefits in PPG control. It is proposed that an aggressive treatment approach focusing on PPG, similar to the current standards for diabetic pregancies, be directed at individuals with diabetes and impaired glucose tolerance.

Cardiovascular Diseases↗
PubMed2006

Run-to-run control of blood glucose concentrations for people with Type 1 diabetes mellitus.

Run-to-run control has been applied to several traditional batch processes in the chemical industry. The 24-h cycle of eating meals, measuring blood glucose concentrations, and delivering the correct insulin bolus, with the goal of achieving the optimal blood glucose profile, can be viewed in the same spirit as traditional batch processes such as emulsion polymerization. In this paper, we aim to exploit the "repetitive" nature of the insulin therapy of people with Type 1 diabetes. A run-to-run algorithm is used on a virtual diabetic patient model to control blood glucose concentrations. The insulin input is parameterized into the timing and amount of the dose while the glucose output is parameterized into the maximum and minimum glucose concentrations. Robustness of the algorithm to variations in the meal amount, meal timing, and insulin sensitivity parameter is addressed. In general, the algorithm is able to converge when the meal timing is varied within +/- 40 min. If the meal size is underestimated by approximately 10 grams (g), the algorithm is able to converge within a reasonable time frame for breakfast, lunch, and dinner. If the meal size is overestimated by 20-25 g, the algorithm is able to converge. When random variations in the meal timing and the meal amount are introduced, the variation on the output variables, Gmax and Gmin, scales according to the amount of variation allowed. Along with this, the insulin sensitivity of the virtual patient model is varied. The algorithm is robust for differences in insulin sensitivity less than +/- 50% of the nominal value.

Blood Glucose↗
PubMed2006

Relationship of fasting and hourly blood glucose levels to HbA1c values: safety, accuracy, and improvements in glucose profiles obtained using a 7-day continuous glucose sensor.

OBJECTIVE: In this study, we evaluated the safety and efficacy of 7-day transcutaneous, real-time, continuous glucose monitoring (CGM) in subjects with insulin-requiring diabetes. RESEARCH DESIGN AND METHODS: Eighty-six subjects were enrolled at five U.S. centers. Subjects wore a sensor inserted under the skin of the abdomen for 7 days during each of three consecutive periods. Data were blinded during period 1 and unblinded during periods 2 and 3. RESULTS: Of the 6,811 matched self-monitoring of blood glucose to sensor values prospectively analyzed, 97.2% fell in the Clarke error grid zones A and B, and median absolute relative difference was 11.4%. After unblinding, subjects reduced time spent at <55 mg/dl by 0.3 h/day, reduced time spent at >240 mg/dl by 1.5 h/day, and increased time in the target zone (81-140 mg/dl) by 1.4 h/day (P < 0.05 for all three comparisons). Improvements were seen in both types 1 and 2 diabetes and with use of both multiple daily injections and continuous subcutaneous insulin infusion. Modal day graphs were generated in six groups of subjects based on HbA1c (A1C) ( 10%). Mean glucose levels from midnight to 7:00 a.m. (fasting and dawn phenomenon periods) were only normal for subjects with A1C <or=6%. All other groups were hyperglycemic during this and all periods. Reductions in overall mean glucose were achieved for the four highest A1C groupings with unblinded device use. CONCLUSIONS: This is the first report of a real-time, transcutaneous glucose sensor that functioned for 7 days. The use of CGM in the unblinded phase resulted in improvements in target-range glycemia across all A1C values.

Blood Glucose↗
PubMed2006

Improvement in glycemic excursions with a transcutaneous, real-time continuous glucose sensor: a randomized controlled trial.

OBJECTIVE: Hypoglycemia and wide glucose excursions continue to be major obstacles to achieving target HbA(1c) values and the associated reductions in long-term complications (and economic costs) in people with insulin-treated diabetes. In this study we evaluated the accuracy, safety, and clinical effectiveness of a continuous glucose-sensing device. RESEARCH DESIGN AND METHODS: A total of 91 insulin-requiring patients with type 1 (n = 75) and type 2 (n = 16) diabetes were enrolled in this multicenter randomized study. Subjects wore a transcutaneous, 3-day, continuous glucose-sensing system for three consecutive 72-h periods. Subjects were randomly assigned (1:1 ratio) to either a control group (continuous glucose data not provided) or a display group (continuous glucose data not provided during period 1 but displayed during periods 2 and 3). During periods 2 and 3, patients in the display group had real-time access to sensor glucose values, could review glucose trends over the preceding 1, 3, and 9 h, and were provided with high (> or = 200 mg/dl) and low (< or = 80 mg/dl) alerts and a low (< or = 55 mg/dl) alarm. Sensors were inserted by patients, and both groups used (or wore) the system during daily activities. Device accuracy was assessed by comparing continuous glucose values to paired self-monitoring of blood glucose (SMBG) meter readings. Clinical effectiveness was evaluated by analyzing between-group (control vs. display, periods 2 and 3) and within-group (display, period 1 vs. period 3) differences in time spent in high, low, and target (81-140 mg/dl) glucose zones. RESULTS: When prospective, real-time sensor values were compared with SMBG values, 95.4% of 6,767 paired glucose values fell within Clarke error grid A and B zones. Pearson's correlation coefficient was 0.88, and mean and median absolute relative differences were 21.2 and 15.9%, respectively. No systematic bias was detected at any of the prespecified glucose levels (50, 80, 100, 150, and 200 mg/dl). When compared with control subjects, the display group spent 21% less time as hypoglycemic (<55 mg/dl), 23% less time as hyperglycemic (> or = 240 mg/dl), and 26% more time in the target (81-140 mg/dl) glucose range (P < 0.001 for each comparison). Nocturnal (10:00 p.m. to 6:00 a.m.) hypoglycemia, as assessed at two thresholds, was also reduced by 38% (<55 mg/dl; P < 0.001) and 33% (55-80 mg/dl; P < 0.001) in the display group compared with control subjects. CONCLUSIONS: We conclude that real-time continuous glucose monitoring for periods up to 72 h is accurate and safe in insulin-requiring subjects with type 1 and type 2 diabetes. This study demonstrates that availability of real-time, continuously measured glucose levels can significantly improve glycemic excursions by reducing exposure to hyperglycemia without increasing the risk of hypoglycemia, which may reduce long-term diabetes complications and their associated economic costs.

Adult↗
PubMed2006

The fidgety fetus hypothesis: fetal activity is an additional variable in determining birth weight of offspring of women with diabetes.

OBJECTIVE: To determine whether some offspring of women with diabetes are intrinsically more active than others in utero and whether those who are active are able to normalize their birth weight despite maternal hyperglycemia. RESEARCH DESIGN AND METHODS: We conducted a three-phase study to view the relationship between fetal movements and subsequent birth weight in women with diabetes. Phase I was designed to assess maternal perception of fetal movements in a population of 10 women with diabetes. To improve our fetal monitoring techniques, in phase II we analyzed fetal movements using the Card Guard home fetal monitoring device (CG 900P) in a population of 13 women with gestational diabetes mellitus (GDM). To apply our observations of fetal movements to a larger population, during phase III we conducted a retrospective analysis of fetal monitoring strips (HP 8041A) from 46 women with GDM to examine the relationship between fetal heart rate (FHR) accelerations and percentile birth weight, corrected for gestational age. RESULTS: Phase I confirmed that there is little variability in fetal movements (i.e., fetal kicks did not significantly deviate from one another on a day-to-day basis). In phase II, the fetal monitoring strips illustrated that the active fetuses (defined as > or = 4 FHR accelerations in a 20-min period) were always active, and the inactive fetuses were always inactive. The mean birth weight percentile, corrected for gestational age, in the active group was 37 vs. 63% in the inactive group (P = 0.05). In phase III, the fetal monitoring strips showed an inverse correlation between the mean number of FHR accelerations and the birth weight of the fetus, corrected for gestational age. The mean birth weight percentile in the active group was 37 vs. 62% in the inactive group (P = 0.0017). CONCLUSIONS: The fetus appears to play a role in determining its own destiny. Increased fetal activity may minimize the impact of hyperglycemia on subsequent birth weight. The inactive fetus appears to be at a higher risk for glucose-mediated macrosomia.

Adult↗
PubMed2005

Run-to-run control of meal-related insulin dosing.

BACKGROUND: This study was designed to determine if it was feasible to use a run-to-run algorithm to improve postprandial glucose concentrations in individuals with type 1 diabetes mellitus (T1DM). METHODS: Fourteen subjects were recruited for this 10-week study. During the initial phases of the study, the following information was derived for each subject: basal insulin infusion rates, insulin-to-carbohydrate ratios, insulin correction factors for hyperglycemia, and insulin sensitivities. During the final phases, the algorithm was used to suggest preprandial insulin doses, with a goal of bringing the postprandial glucose into a predetermined target range within 3-7 days. RESULTS: In the single-meal phase (phase 5), 33% of the subject-meal responses were convergent in 3-4 days to a clinically acceptable range, 33% always stayed in range, and 33% had divergent responses, incorrect sensitivities, and/or other mitigating circumstances. In the three-meal phase (phase 6), 41% of the subject-meal responses were convergent in 3-4 days to a clinically acceptable range, 26% were always in range, and 33% had divergent responses, incorrect sensitivities, and/or other mitigating circumstances. CONCLUSIONS: Overall, we were able to safely demonstrate that run-to-run control can be used to manage meal-related insulin in subjects with T1DM.

Algorithms↗
PubMed2005

Decreasing the risk of diabetic retinopathy in a study of case management: the California Medi-Cal Type 2 Diabetes Study.

OBJECTIVE: Diabetic retinopathy affects >60% of people with type 2 diabetes during the first 2 decades of the disease and is ameliorated by good glycemic control. This study tested whether intensive diabetes case management could prevent or delay diabetic retinopathy in patients with established type 2 diabetes. RESEARCH DESIGN AND METHODS: This study was part of a randomized, controlled clinical trial of diabetes case management in type 2 diabetes in southern California counties serving low income ethnic minority populations. Subjects were randomized to intervention (diabetes case management) or control (traditional treatment) groups. Subjects with at least two retinal photographs (n = 149) were included in this analysis to assess the effect of intervention on development or progression of diabetic retinopathy. RESULTS: Progression of retinopathy in the intervention group was not significantly less than in the control group (P = 0.226). However, those in the intervention group with no evidence of retinopathy at baseline were less likely to develop diabetic retinal changes (5/48) during a mean follow-up of 23.1 months than those in the control group (10/34, chi(2) = 4.805, P = 0.028). This difference remained significant in a logistic regression model that controlled for potential confounders (odds ratio 5.35 [95% CI 1.14-25.12]). CONCLUSIONS: This study shows that a relatively short duration of case management instituted before the onset of clinically identifiable retinopathy significantly diminished the risk of developing retinopathy in patients with type 2 diabetes. The findings also emphasized the retinal disease burden in this population, with development and progression of retinopathy occurring in <2 years.

Adult↗
PubMed2005

Elevated pregnancy losses at high and low extremes of maternal glucose in early normal and diabetic pregnancy: evidence for a protective adaptation in diabetes.

OBJECTIVE: Early pregnancy losses increase with marked hyperglycemia in diabetic pregnancy. However, mean loss rates do not differ from those of nondiabetic pregnancy. This observation might be explained by increased fetal losses at the extremes of glycemia in diabetic and nondiabetic pregnancy. To test this hypothesis, we examined relationships of proximate measures of prior glycemia, glycated protein and fructosamine, to pregnancy loss. RESEARCH DESIGN AND METHODS: A total of 389 diabetic and 429 nondiabetic pregnant subjects participated in the Diabetes In Early Pregnancy study. Glycated protein and fructosamine measurements were standardized as multiples of control values for each center (Z score). The logarithm of odds of pregnancy loss were plotted against Z scores and tested by logistic models. RESULTS: Mean pregnancy loss rates were 12% in diabetic and 13% in normal pregnancies. However, over six intervals of glycated protein in diabetic pregnancy, fetal loss rates at the upper and lower extremes (24 and 33%, respectively) were approximately threefold higher than the four intervening rates (8-14%). The odds ratio of pregnancy loss for these extreme intervals to the intervening intervals is 3.0 (P = 0.01). Nondiabetic losses showed a similar pattern. In confirmation, logit pregnancy losses were increased in a J-shaped curve at the glycemic extremes in normal (P < 0.019) and diabetic (P < 0.015) pregnancy. The upper glycemic extreme in diabetic pregnancy was two- to fivefold higher than in control pregnancy. CONCLUSIONS: Pregnancy losses are increased at the extremes of glycemia in both normal and diabetic pregnancy but at higher levels in diabetic pregnancy. The data suggest defensive adaptations against hyperglycemia in diabetic pregnancy.

Abortion, Spontaneous↗
PubMed2005

Efforts to improve subsequent treatment of cardiovascular risk factors in older patients with diabetes hospitalized for a cardiac event.

OBJECTIVE: To improve the treatment of risk factors of cardiovascular disease (CVD) for older patients with diabetes after a cardiac event by using a low-literacy reminder card describing these risk factors in community settings. STUDY DESIGN: A multicenter, randomized, interventional study. METHODS: Patients aged 55 years or older with diabetes hospitalized with an acute myocardial infarction, congestive heart failure exacerbation, or unstable angina were eligible to enter the study. Control and experimental patients were recruited from 4 sites and were enrolled in the study before discharge from the hospital. Experimental subjects received education and a reminder card describing risk factors of CVD. They were instructed to discuss the risk factors described on the reminder card with their primary care physician on their first appointment after discharge. Control subjects did not receive any intervention but were given consent to be able to review their charts. RESULTS: One hundred sixty patients completed the study, 82 in the control group and 78 in the experimental group. At the end of the study there was no difference in blood pressure control, lipid levels, and glycosylated hemoglobin levels between the control and experimental patients. Aspirin use and ACE inhibitor use were found to be significantly higher in the control group (P = .001 and .03, respectively). CONCLUSIONS: Reminder cards given to patients to discuss with their primary care providers in community settings did not improve process measures of CVD risk in patients with documented CVD and diabetes. Other approaches will be needed to improve the treatment of risk factors in these high-risk patients.

Aged↗
PubMed2004

Advances in diabetes for the millennium: diabetes in minorities.

Diabetes shows an increased prevalence among minority groups, including Asians, African Americans, Hispanics, Native Americans, and Pacific Islanders. The sedentary lifestyle and high-fat diet of modern industrialized societies promote obesity at an early age. There is a strong correlation between the development of diabetes and increased visceral adiposity in American minority groups. This review focuses on the 2 largest minority groups in the United States, African Americans and Hispanics. The risk of diabetes is 20% to 50% greater in African American men and twice as great in African American women as well as twice as high in Hispanic adults than in whites. Furthermore, the prevalence of diabetes-associated complications, such as retinopathy and amputations, is 50% to 100% higher in African Americans and Hispanics. The unfavorable consequences of diabetes in African American and Hispanic individuals do not seem to be due to inherent biological differences. Rather, it appears that differences in medical care and self-management of diabetes may be the major factor. The key to improving outcomes in these minority groups lies in enhancement of communication to overcome barriers to self-care. It is important to better understand the cultural milieu in minority communities to enhance patient involvement in their own management. Where this has been done, marked improvements in diabetes healthcare have occurred.

Black or African American↗
PubMed2004

Advances in diabetes for the millennium: diabetes in women.

Diabetes mellitus may afflict men and women equally, but the suffering associated with diabetes when it appears in a woman affects every aspect of her life. As a young child, her growth and development as well as her emotional and intellectual functioning may be impaired. In addition, her puberty may be delayed or premature, and when she is ready for childbearing, her health may preclude a successful pregnancy and/or her chances of bearing a healthy child may be poor to impossible. With the advent of insulin and treatment programs to improve glucose control, the diabetic woman now has an opportunity to lead a near-normal life. As devices have automated insulin delivery and as the use of self-blood glucose monitoring has assisted in deriving a protocol of safely normalizing blood glucose, the health of a diabetic woman now is equal to her nondiabetic sister. This review outlines the rationale of programs of normalized glycemia for diabetic women and suggests strategies to achieve success.

Adolescent↗