Biomedical subjects

Christine Darwin

Publications and source records attributed to Christine Darwin.

7 recordsLinked to original sources

PubMed2006

Measurement of brain metabolites in patients with type 2 diabetes and major depression using proton magnetic resonance spectroscopy.

Type 2 diabetes and major depression are disorders that are mutual risk factors and may share similar pathophysiological mechanisms. To further understand these shared mechanisms, the purpose of our study was to examine the biochemical basis of depression in patients with type 2 diabetes using proton MRS. Patients with type 2 diabetes and major depression (n=20) were scanned along with patients with diabetes alone (n=24) and healthy controls (n=21) on a 1.5 T MRI/MRS scanner. Voxels were placed bilaterally in dorsolateral white matter and the subcortical nuclei region, both areas important in the circuitry of late-life depression. Absolute values of myo-inositol, creatine, N-acetyl aspartate, glutamate, glutamine, and choline corrected for CSF were measured using the LC-Model algorithm. Glutamine and glutamate concentrations in depressed diabetic patients were significantly lower (p<0.001) in the subcortical regions as compared to healthy and diabetic control subjects. Myo-inositol concentrations were significantly increased (p<0.05) in diabetic control subjects and depressed diabetic patients in frontal white matter as compared to healthy controls. These findings have broad implications and suggest that alterations in glutamate and glutamine levels in subcortical regions along with white matter changes in myo-inositol provide important neurobiological substrates of mood disorders.

Adult↗

PubMed2006

Cognitive function in adults with type 2 diabetes and major depression.

The aim of this study was to identify characteristics of neuropsychological functioning among type 2 diabetic adults with and without major depression. Twenty type 2 diabetics with major depression, 20 non-depressed type 2 diabetics and 34 controls without diabetes or depression were compared. A mixed effects repeated measures analysis of covariance indicated significant differences in overall cognitive functioning between diagnostic groups, specifically depressed diabetics demonstrated greater cognitive dysfunction than controls. Further comparisons indicated that depressed diabetics performed significantly worse than non-depressed diabetics in attention/information processing speed. Relative to controls, depressed diabetics performed significantly worse in attention/information processing speed and executive functioning, while there was a trend for non-depressed diabetics to perform worse in executive functioning. These findings suggest that depression negatively impacts cognitive performance among adults with type 2 diabetes, which may have implications for neural circuitry underlying cognitive and mood changes in diabetic patients.

Adult↗

PubMed2006

Feasibility of automating insulin delivery for the treatment of type 1 diabetes.

An automated closed-loop insulin delivery system based on subcutaneous glucose sensing and subcutaneous insulin delivery was evaluated in 10 subjects with type 1 diabetes (2 men, 8 women, mean [+/-SD] age 43.4 +/- 11.4 years, duration of diabetes 18.2 +/- 13.5 years). Closed-loop control was assessed over approximately 30 h and compared with open-loop control assessed over 3 days. Closed-loop insulin delivery was calculated using a model of the beta-cell's multiphasic insulin response to glucose. Plasma glucose was 160 +/- 66 mg/dl at the start of closed loop and was thereafter reduced to 71 +/- 19 by 1:00 p.m. (preprandial lunch). Fasting glucose the subsequent morning on closed loop was not different from target (124 +/- 25 vs. 120 mg/dl, respectively; P > 0.05). Mean glucose levels were not different between the open and closed loop (133 +/- 63 vs. 133 +/- 52 mg/dl, respectively; P > 0.65). However, glucose was within the range 70-180 mg/dl 75% of the time under closed loop versus 63% for open loop. Incidence of biochemical hypoglycemia (blood glucose <60 mg/dl) was similar under the two treatments. There were no episodes of severe hypoglycemia. The data provide proof of concept that glycemic control can be achieved by a completely automated external closed-loop insulin delivery system.

Adult↗

PubMed2005

Cosegregation of albuminuria and blood pressure: the Insulin Resistance Atherosclerosis (IRAS) family study.

BACKGROUND: Albuminuria was shown to be heritable and to share common genetic determinants with blood pressure (BP) in individuals of white ethnicity. Our aim in this study was to examine the familial aggregation of albuminuria and its phenotypic, genetic, and environmental correlations with BP in nondiabetic individuals of Hispanic (HA) and African American (AA) ethnicity. METHODS: The study included 129 large HA and AA families, providing 1405 nondiabetic individuals; those on antihypertensive medications were excluded. The albumin/creatinine ratio (ACR) in a random urine sample was used as a measure of albuminuria. A variance component approach was used in the analysis. RESULTS: After adjusting for age, sex, and body mass index (BMI), the heritabilities of ACR, systolic BP (SBP) and diastolic BP (DBP) were 11%, 26%, and 28%. The phenotypic correlations between ACR and each of SBP and DBP in HA (r = 0.17 and r = 0.16 respectively) and AA (r = 0.26 and r = 0.16) were significant. When partitioned into genetic and environmental factors, the genetic correlations between ACR and each of SBP and DBP were significant in HA (r(g) = 0.49 for each), whereas the environmental correlations were not. Conversely, the genetic correlations between ACR and SBP/DBP were not significant in AA (although with DBP it was not significantly different from that of HA), whereas a significant environmental correlation was observed between ACR and SBP (r(e) = 0.28, P < .001). CONCLUSIONS: Both albuminuria and BP exhibit familial aggregation in nondiabetic HA and AA. In HA, but not in AA, ACR and especially SBP share common genetic determinants. The mechanism of this ethnic heterogeneity is unclear but merits further investigation.

Adult↗

PubMed2004

Elevated serum parathyroid hormone concentration in eucalcemic patients after parathyroidectomy for primary hyperparathyroidism and its relationship to vitamin D profile.

Elevation of serum parathyroid hormone (PTH) level in eucalcemic patients after parathyroidectomy for primary hyperparathyroidism has been described in up to 40% of patients, but little is known about its etiology or clinical significance. To better understand the cause of this phenomenon, we studied 49 patients without renal dysfunction or osteomalacia who underwent parathyroidectomy for primary hyperparathyroidism. Patients were categorized into 2 groups based on their serum PTH and calcium levels after parathyroidectomy: (1) elevated PTH with eucalcemia (n = 21), (2) normal PTH with eucalcemia (n = 28). Elevation of serum PTH with eucalcemia after parathyroidectomy occurred in 43% of patients. Patients in group 1 had significantly higher preoperative and postoperative mean serum PTH levels and significantly lower postoperative serum levels of 1,25(OH)(2)D(3), 1,25(OH)(2)D(3)/25(OH)D(3) ratio, and 1,25(OH)(2)D(3)/PTH ratio compared with patients in group 2. Serum PTH in group 1 patients normalized as early as 3 months, but remained elevated in some patients for more than 4 years, and was not associated with development of recurrent hypercalcemia. Normalization of serum PTH in group 1 patients was associated with significant increase in 1,25(OH)(2)D(3) and 1,25(OH)(2)D(3)/PTH ratio. Our data suggest that elevation of serum PTH in eucalcemic patients after parathyroidectomy is a frequently reversible state of resistance of the kidneys to PTH-mediated 1-alpha hydroxylation of 25(OH)D(3) and does not signify subsequent recurrence of hyperparathyroidism.

Bone Density↗

PubMed2004

Evaluation of insulin sensitivity and beta-cell function indexes obtained from minimal model analysis of a meal tolerance test.

Modeling analysis of glucose, insulin, and C-peptide following a meal has been proposed as a means to estimate insulin sensitivity (S(i)) and beta-cell function from a single test. We compared the model-derived meal indexes with analogous indexes obtained from an intravenous glucose tolerance test (IVGTT) and hyperglycemic clamp (HGC) in 17 nondiabetic subjects (14 men, 3 women, aged 50 +/- 2 years [mean +/- SE], BMI 25.0 +/- 0.7 kg/m(2)). S(i) estimated from the meal was correlated with S(i) estimated from the IVGTT and the HGC (r = 0.59 and 0.76, respectively; P < 0.01 for both) but was approximately 2.3 and 1.4 times higher (P < 0.05 for both). The meal-derived estimate of the beta-cell's response to a steady-state change in glucose (static secretion index) was correlated with the HGC second-phase insulin response (r = 0.69; P = 0.002), but the estimated rate-of-change component (dynamic secretion index) was not correlated with first-phase insulin release from either the HGC or IVGTT. Indexes of beta-cell function obtained from the meal were significantly higher than those obtained from the HGC. In conclusion, insulin sensitivity and beta-cell indexes derived from a meal are not analogous to those from the clamp or IVGTT. Further work is needed before these indexes can be routinely used in clinical and epidemiological studies.

Blood Glucose↗

PubMed2003

Modeling beta-cell insulin secretion--implications for closed-loop glucose homeostasis.

Glucose sensing and insulin delivery technology can potentially be linked to form a closed-loop insulin delivery system. Ideally, such a system would establish normal physiologic glucose profiles. To this end, a model of beta-cell secretion can potentially provide insight into the preferred structure of the insulin delivery algorithm. Two secretion models were evaluated for their ability to describe plasma insulin dynamics during hyperglycemic clamps (humans; n=7), and for their ability to establish and maintain fasting euglycemia under conditions simulated by the minimal model. The first beta-cell model (SD) characterized insulin secretion as a static component that had a delayed response to glucose, and a dynamic component that responded to the rate of increase of glucose. The second model (PID) described the response in terms of a proportional component without delay, an integral component that adjusted basal delivery in proportion to hyper/hypoglycemia, and a derivative component that responded to the rate of glucose change. Both models fit the beta-cell response during the clamp, and established fasting euglycemia under simulated closed-loop conditions; however, the SD model did not maintain euglycemia following simulated changes in insulin sensitivity or glucose appearance, whereas the PID model did. The PID model was more stable under the simulated closed-loop conditions. Both the SD and PID models described beta-cell secretion in response to a rapid increase in glucose. However, the PID model could maintain fasting euglycemia and was more stable under closed-loop conditions, and thus is more suited for such conditions.

Algorithms↗