Brain Glucose Metabolism in Noninsulin-Dependent Diabetes Mellitus: A Study in Pima Indians Using Positron Emission Tomography during Hyperinsulinemia with Euglycemic Glucose Clamp

Abstract

To determine whether insulin or noninsulin-dependent diabetes mellitus affects brain glucose metabolism, brain glucose utilization was studied in the basal state and during hyperinsulinemic euglycemic glucose clamps in nondiabetic and diabetic Pima Indians by positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (18FDG). Glucose utilization in 75 brain areas was determined by analysis of single scans and by least squares estimation of the rate parameters for the FDG model; these data were compared to results in normal caucasian volunteers. No effect of ethnicity or diabetic status on brain glucose utilization was observed. During the hyperinsulinemic clamps (mean insulin, 11,708 +/- 3,026 pmol/L), clearance of 18FDG from blood was accelerated, and accumulation of brain radioactivity was reduced. However, glucose utilization by the brain was identical to results during sham glucose clamps (mean insulin, 204 +/- 56 pmol/L) performed in the same patients. During the studies with hyperinsulinemia, k4 (representing loss of tissue radioactivity) was increased in most brain areas (mean increase, 0.0031 +/- 0.0018 min-1; P less than 0.02). The possible mechanisms for this effect are multiple, and the physiological significance, if any, is unknown. Further studies of the effects of insulin on brain glucose metabolism are needed.

Insulin Resistance and Alzheimer-like Reductions in Regional Cerebral Glucose Metabolism for Cognitively Normal Adults With Prediabetes or Early Type 2 Diabetes

“…In an early FDG-PET study in humans, a small sample of Pima Indians with T2D (n=4) showed no overall differences compared with caucasian participants without T2D 20. Regional differences were not examined, however, and the diabetic group was heterogenous with respect to treatment.…”

Blood-to-Brain Glucose Transport, Cerebral Glucose Metabolism, and Cerebral Blood Flow Are Not Increased After Hypoglycemia

“…It has also been applied to an earlier study in humans showing that neither blood-to-brain glucose transport nor cerebral glucose metabolism is reduced in poorly controlled type 1 diabetes (24). It differs from other PET methods (42)(43)(44) in that it uses both [ 11 C]glucose labeled in the C-1 position and a model that includes a fourth rate constant to account for the egress of […”

Why is learning and memory dysfunction in Type 2 diabetes limited to older adults?

“…Conversely, chronic hyperglycaemia is a de®ning characteristic of Type 2 diabetes, and it is likely that the link between diabetes and CNS dysfunction is mediated by the family of metabolic derangements associated with chronically elevated blood glucose levels [34,35]. Regional cerebral blood¯ow often decreases during chronic (and acute) hyperglycaemia in animals [36], and abnormalities in brain uptake and metabolism of glucose have been reported inconsistently in older adults with Type 2 diabetes [37,38]. Aminergic neurotransmitter pathways (including norepinephrine, dopamine and serotonin) are also known to be affected by diabetes, but again virtually all of these studies have been conducted on animal models of diabetes (for reviews see McCall [39]).…”