Cerebral blood flow and substrate utilization in insulin-treated diabetic subjects

Grill, Valdemar; Gutniak, M.; Björkman, Ola; Lindqvist, M.; Stone‐Elander, Sharon; Seitz, R. J.; Blomqvist, G.; Reichard, Per; Widén, L.

doi:10.1152/ajpendo.1990.258.5.e813

Cited by 40 publications

(31 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Samples were also taken at timed intervals to measure the arterial concentrations of ␤-HB, glucose, lactate, glycerol, and insulin, and also to determine hematocrit, pH, and standard bicarbonate concentration. The different concentrations were determined by standard methods, as described by Grill et al (6).…”

Section: Methodsmentioning

confidence: 99%

Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in nondiabetic subjects and IDDM patients

Blomqvist

Alvarsson²,

Grill

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

Section: Methodsmentioning

confidence: 99%

Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in nondiabetic subjects and IDDM patients

Blomqvist

Alvarsson²,

Grill

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

“…Disease variables were either classified as dichotomous variables (e.g., the presence or absence of a history of severe hypoglycemic episodes) or as continuous variables (e.g., duration of diabetes in years). Studies that assessed the (1,3,18,19,20 -32), b ϭ (18,19,22,27,29, c ϭ (6,18,19,25), d ϭ (3,6,18,20,22,23,25,31), e ϭ (6,18,22,25,29), f ϭ (3,6,18,22,25), g ϭ (6,22,25,29), h ϭ (3,22,25), i ϭ (3,6,18,19,21,22,25,30), j ϭ (20,24,28,29,32), k ϭ (20,27), l ϭ (2,3,21,25,29), m ϭ (18,27,29)...…”

Section: Selection Of Studiesmentioning

confidence: 99%

The Effects of Type 1 Diabetes on Cognitive Performance

et al. 2005

View full text Add to dashboard Cite

OBJECTIVE -To investigate the exact nature and magnitude of cognitive impairments in patients with type 1 diabetes and the possible association with other disease variables, such as recurrent episodes of hypoglycemia and metabolic control.RESEARCH DESIGN AND METHODS -MedLine and PsycLit search engines were used to identify studies on cognitive performance in patients with type 1 diabetes. Effect sizes (Cohen's d), which are the standardized differences between the experimental and the control group, were calculated. In the meta-analysis, a combined d value was calculated, expressing the magnitude of associations across studies.RESULTS -A total of 33 studies were identified that met the inclusion criteria. Compared with nondiabetic control subjects, the type 1 diabetic group demonstrated a significantly lowered performance on the following cognitive domains: intelligence (d ϭ Ϫ0.7), speed of information processing (d ϭ Ϫ0.3), psychomotor efficiency (d ϭ Ϫ0.6), visual (d ϭ Ϫ0.4) and sustained attention (d ϭ Ϫ0.3), cognitive flexibility (d ϭ Ϫ0.5), and visual perception (d ϭ Ϫ0.4). Lowered cognitive performance in diabetic patients appeared to be associated with the presence of microvascular complications but not with the occurrence of severe hypoglycemic episodes or with poor metabolic control.CONCLUSIONS -In patients with type 1 diabetes, cognitive dysfunction is characterized by a slowing of mental speed and a diminished mental flexibility, whereas learning and memory are spared.The magnitude of the cognitive deficits is mild to moderate, but even mild forms of cognitive dysfunction might hamper everyday activities since they can be expected to present problems in more demanding situations. Diabetes Care 28:726 -735, 2005

show abstract

“…Several studies have found that intensively treated patients with type 1 diabetes have cortical metabolic adaptations during hypoglycemia. Positron emission tomography (PET) and arterio-venous difference studies have found that in contrast to control subjects who show a 20 -30% decrease in glucose uptake during moderate hypoglycemia (ϳ2.8 mmol/l), subjects with intensively treated type 1 diabetes show minimal reduction in glucose uptake (5)(6)(7)(8).…”

mentioning

confidence: 99%

“…As early as 1990, Grill et al (7) proposed that this adaptation may largely be due to increased utilization of alternate substrates to glucose, based on the finding that under euglycemic conditions glucose uptake was lower in the subjects with type 1 diabetes. Although glucose is the major substrate supporting metabolism in the central nervous system, under certain conditions, such as starvation, the brain can adapt to use alternative substrates such as ketones and lactate to meet its energy requirements (12)(13)(14).…”

mentioning

confidence: 99%

“…We and others have previously shown that acetate labeled with the stable isotope 13 C is an effective and relatively low-cost tracer for 13 C magnetic resonance spectroscopy (MRS) studies in humans (17). Analysis of 13 C labeling curves of glutamate, glutamine, and acetate during an infusion of [2][3][4][5][6][7][8][9][10][11][12][13] C]acetate allows determination of acetate transport and metabolism as well as relative rates of the glial and neuronal TCA cycle and glutamate/glutamine cycling to be calculated (18). In the present study, we used 13 C MRS in combination with infusion of [2-13 C] acetate to test the hypothesis that upregulation of transport and utilization of MCAs (acetate, acetoacetate, ␤-hydroxybutyrate, and lactate) in the brains of subjects with type 1 diabetes, who have previously experienced hypoglycemia associated with insulin use, might provide some substrate for energy generation as an alternative to glucose for brain metabolism.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Increased Brain Monocarboxylic Acid Transport and Utilization in Type 1 Diabetes

Mason

Petersen

Lebon³

et al. 2006

Diabetes

116

113

View full text Add to dashboard Cite

We hypothesized that increased capacity for brain utilization of nonglucose substrates (monocarboxylic acids [MCAs]) by upregulation of the MCA transporters may contribute metabolic substrates during hypoglycemia. To test this hypothesis, we assessed brain acetate metabolism in five well-controlled type 1 diabetic subjects and six nondiabetic control subjects using 13 C magnetic resonance spectroscopy during infusions of [2-13 C]acetate during hypoglycemia (ϳ55 mg/dl). Acetate is transported into the brain through MCA transporters that are also used for lactate and ketones. Brain acetate concentrations were over twofold higher in the subjects with diabetes than the control subjects (P ‫؍‬ 0.01). The fraction of oxidative metabolism from acetate (P ‫؍‬ 0.015) and the rate of MCA transport (P ‫؍‬ 0.01) were also approximately twofold higher in the diabetic subjects. We conclude that during hypoglycemia MCA transport in the brain was increased by appoximately twofold in patients with well-controlled type 1 diabetes, as reflected by higher brain acetate concentrations and rates of acetate oxidation. This upregulation would potentially allow a similar twofold increase in the transport of other MCAs, including lactate, during insulininduced hypoglycemia. These data are consistent with the hypothesis that upregulation of MCA transport may contribute to the maintenance of brain energetics during hypoglycemia in patients with type 1 diabetes. Diabetes 55: 929 -934, 2006 U nder normal, nonfasting conditions, oxidation of glucose is the main source of energy for brain function (1). In intensively treated subjects with type 1 diabetes, there is often a loss of both the counterregulatory response and the mild cognitive symptoms before severe cognitive dysfunction (2,3). Both of these adaptations are believed to significantly contribute to hypoglycemic unawareness, which increases the risk of severe hypoglycemia, which may result in seizure or coma (4). The loss of cognitive symptoms is believed to be, at least in part, secondary to adaptations that allow brain energy metabolism to be maintained during moderate hypoglycemia (5). Several studies have found that intensively treated patients with type 1 diabetes have cortical metabolic adaptations during hypoglycemia. Positron emission tomography (PET) and arterio-venous difference studies have found that in contrast to control subjects who show a 20 -30% decrease in glucose uptake during moderate hypoglycemia (ϳ2.8 mmol/l), subjects with intensively treated type 1 diabetes show minimal reduction in glucose uptake (5-8).Several hypotheses have been proposed to explain this metabolic adaption, particularly increased brain glucose transport, based on studies in rat models that showed an increase in glucose transporter activity in rats exposed to prolonged hypoglycemia (rev. in 9), but this concept is controversial. Studies of humans with diabetes have generally not been able to establish a change in transport parameters in poorly controlled and well-controlled patients. The study ...

show abstract

Cerebral blood flow and substrate utilization in insulin-treated diabetic subjects

Cited by 40 publications

References 16 publications

Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in nondiabetic subjects and IDDM patients

Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in nondiabetic subjects and IDDM patients

The Effects of Type 1 Diabetes on Cognitive Performance

Increased Brain Monocarboxylic Acid Transport and Utilization in Type 1 Diabetes

Contact Info

Product

Resources

About