Elevated rates of basal hepatic glucose output (bHGO) are significantly correlated with the fasting serum glucose (FSG) level in subjects with non-insulin-dependent diabetes mellitus (NIDDM). This observation suggests that bHGO is a major determinant of the severity of the diabetic state in these subjects. In addition, basal glucagon levels (bGL) are higher in these diabetics than in control subjects, despite the concurrent basal hyperglycemia and hyperinsulinemia, two factors known to suppress glucagon secretion. Although bGL is responsible for sustaining two-thirds of bHGO in normal humans, its role in sustaining elevated rates of bHGO in NIDDM has not been previously defined. To this end, we have studied 13 normal and 10 NIDDM subjects; mean FSG levels were 90 +/- 2 and 262 +/- 21 mg/dl, respectively (P less than .001). The mean fasting serum insulin and glucagon levels were higher in the diabetics than in the controls: 17 +/- 2 vs. 9 +/- 1 microU/ml (P less than .01) and 208 +/- 37 vs. 104 +/- 15 pg/ml (P less than .01), respectively. On separate days, HGO was assessed isotopically (with 3-[3H]glucose) in the basal state and during infusion of somatostatin (SRIF) (600 micrograms/h) alone and in conjunction with replacement infusions of glucose and insulin. The results demonstrate that bHGO is higher in diabetics than in controls (145 +/- 12 vs. 89 +/- 3 mg X m-2 X min-1, P less than .01); during infusion of SRIF alone, HGO was suppressed by 25% (P less than .05) and 34% (P less than .05) of the basal value in controls and diabetics, respectively; when the studies were repeated with glucose levels held constant at or near the FSG level by the glucose-clamp technique, the pattern and degree of HGO suppression was similar to that obtained by infusion of SRIF alone; during isolated glucagon deficiency (SRIF + insulin, 5 mU X m-2 min-1, with serum glucose maintained at basal level), HGO was suppressed by 71 +/- 8% of the basal value in controls (P less than .001) and by 58 +/- 7% in diabetics (P less than .001); and when isolated glucagon deficiency with similar hyperglycemia was created in control subjects, HGO was suppressed by 87% of the basal value.(ABSTRACT TRUNCATED AT 250 WORDS)
We performed a prospective analysis on 14 11q- patients to determine the relationship between the degree of cognitive impairment and relative deletion size. Seventeen measures of cognitive function were assessed. All nine patients with a deletion of at least 12.1 Mb had severe global cognitive impairment, with full-scale IQ <50, whereas all five patients with smaller deletions, ≤11.8 Mb, demonstrated mild cognitive impairment, with a full-scale IQ of 63 or higher (p < 0.001). Among these five patients, the two patients with the larger deletions (11.4, 11.8 Mb) had a selective impairment in freedom from distractability compared to the three patients with smaller deletions (≤9.1 Mb). We propose the presence of a proximal critical region that contains a gene for global cognitive function and a distal critical region that contains a gene essential for auditory attention, which may be necessary for optimizing intellectual function. The proximal critical region is 300 kb and contains three annotated genes. One of these genes, BSX, encodes a brain-specific homeobox protein that in gene-targeted mice has been shown previously to have a role in regulating locomotory behavior via BSX-expressing neurons in the hypothalamus. The distal critical region, ~2.2 Mb, contains 18 annotated genes. One gene in this region, Neurogranin, has been demonstrated previously in mice to be critical for synapse plasticity and long-term potentiation. Taken together, our results implicate the presence of at least two loci in distal 11q that when deleted, cause global and selective deficits in neurocognitive function. These findings have important implications for genetic counseling and potential gene-specific therapies.
Average age at Dx (SD) was 9.02 yr (4.46)yr; 63.9% were Caucasian, 25% Mexican American (MA), 2.9% African American, 0.7% Asian, and 7.3% mixed. Diabetic ketoacidosis rate was more common in MA (44.1%) vs. Caucasians (20.9%) at Dx (p < 0.02). Average body mass index Z-score (BMI-Z) at Dx was -0.28 (39th percentile); 13.5% had BMI > or = 85th percentile, and 7.2% were obese. By 2 wk, and 15-41 d post-Dx, mean weight gain was 9% (5.9) and 12.8% (8), respectively. Mean A1C at Dx, 42-70 and 71-139 d later, was 11.4, 7.6, and 6.9%, respectively. Coinciding with improved glycemic control, by 10 wk, mean BMI-Z reached a plateau of 0.86 (80th percentile). On average, MA were heavier than Caucasians at Dx (p = 0.006), and remained heavier. By 71-139 d, 31.7% had BMI > or = 85th percentile and 15.9% were obese; 47.8% of 2- to 5-yr olds had BMI > or = 85th percentile vs. 22.6% nationally (p < 0.005) CONCLUSIONS: Despite the initial weight loss at Dx of type 1 diabetes, by 10-20 wk post-Dx, almost one third were overweight and obese, more so in MA. In light of the obesity epidemic, closer attention to overall caloric intake in children with new onset diabetes is prudent.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.