phosphocreatine and Prediabetic-State

In older adults, type-2 diabetes mellitus (T2DM) impacts cognition and increases dementia risk. Prior studies suggest that impaired neuroplasticity may contribute to the cognitive decline in T2DM, but the underlying mechanisms of altered neuroplasticity are unclear. We investigated the relationship of the concentration of glutamatergic metabolites with measures of cortical plasticity in older adults across the spectrum of glucose intolerance/insulin resistance.. Forty adults (50-87 years: 17-T2DM, 14-pre-diabetes, 9-controls) underwent magnetic resonance spectroscopy to quantify glutamate and other key metabolites within a 2 cm. Group differences were observed in relative concentrations of glutamine (p = .028), glucose (p = .008), total cholines (p = .048), and the glutamine/glutamate ratio (p = .024). Cortical plasticity was reduced in both T2DM and pre-diabetes groups relative to controls (p-values < .05). Only the T2DM group showed a significant positive association between glutamate concentration and plasticity (r = .56, p = .030).. Neuroplastic mechanisms are already impaired in pre-diabetes. In T2DM, reduced cortico-motor plasticity is associated with lower cortical glutamate concentration.. Impaired plasticity in T2DM is associated with low glutamatergic metabolite levels. The glutamatergic neurotransmission system constitutes a potential therapeutic target for cognitive problems linked to plasticity-related deficiencies in T2DM.

Topics: Aged; Aged, 80 and over; Aging; Aspartic Acid; Creatine; Diabetes Mellitus, Type 2; Female; Glucose; Glucose Intolerance; Glutamic Acid; Glutamine; Glutathione; Glycerylphosphorylcholine; Humans; Inositol; Insulin Resistance; Magnetic Resonance Spectroscopy; Male; Middle Aged; Motor Cortex; Neuronal Plasticity; Phosphocreatine; Phosphorylcholine; Prediabetic State; Theta Rhythm; Transcranial Magnetic Stimulation

Several lines of evidence support a potential role of skeletal muscle mitochondrial dysfunction in the pathogenesis of insulin resistance and/or type 2 diabetes. However, it remains to be established whether mitochondrial dysfunction represents either cause or consequence of the disease. We examined in vivo skeletal muscle mitochondrial function in early and advanced stages of type 2 diabetes, with the aim to gain insight in the proposed role of mitochondrial dysfunction in the aetiology of insulin resistance and/or type 2 diabetes.. Ten long-standing, insulin-treated type 2 diabetes patients, 11 subjects with impaired fasting glucose, impaired glucose tolerance and/or recently diagnosed type 2 diabetes, and 12 healthy, normoglycaemic controls, matched for age and body composition and with low habitual physical activity levels were studied. In vivo mitochondrial function of the vastus lateralis muscle was evaluated from post-exercise phosphocreatine (PCr) recovery kinetics using (31)P magnetic resonance spectroscopy (MRS). Intramyocellular lipid (IMCL) content was assessed in the same muscle using single-voxel (1)H MRS.. IMCL content tended to be higher in the type 2 diabetes patients when compared with normoglycaemic controls (P=0.06). The(31)P MRS parameters for mitochondrial function, i.e. PCr and ADP recovery time constants and maximum aerobic capacity, did not differ between groups.. The finding that in vivo skeletal muscle oxidative capacity does not differ between long-standing, insulin-treated type 2 diabetes patients, subjects with early stage type 2 diabetes and sedentary, normoglycaemic controls suggests that mitochondrial dysfunction does not necessarily represent either cause or consequence of insulin resistance and/or type 2 diabetes.

Topics: Adenosine Diphosphate; Blood Glucose; Diabetes Mellitus, Type 2; Glucose Intolerance; Humans; Insulin Resistance; Magnetic Resonance Spectroscopy; Middle Aged; Mitochondrial Diseases; Models, Biological; Muscle, Skeletal; Phosphocreatine; Phosphorus Isotopes; Prediabetic State; Severity of Illness Index

In spontaneously diabetic BB rats, the effect of chronically maintained blood glucose levels on the degree of energy failure and brain pH change during an ischemic insult, and on subsequent recovery after reperfusion, was studied with in vivo 31P magnetic resonance spectroscopy. Short duration forebrain ischemia (10-min carotid occlusion plus hypotension of 50 mmHg) was induced in diabetic and nondiabetic male BB rats whose blood glucose levels were maintained with insulin. Spectra were obtained in 1-min blocks before, during, and for 1 h after ischemia. Before ischemia, hypoglycemic (blood glucose less than 3 mM) diabetic rats had an increased Pi peak intensity, with no significant pH change, compared with other groups. During ischemia, the rate and extent of hydrolysis of high-energy phosphate metabolites (as measured by an increase in Pi) decreased, and the severity of tissue acidosis increased as preischemia blood glucose concentration increased. Among hyperglycemic BB rats, similar ischemia-induced changes were found for subgroups with blood glucose levels of 13.7 +/- 1.2 and 20.3 +/- 0.6 mM, in keeping with the known decrease in hexose binding sites associated with chronic hyperglycemia. Decline in PCr level during ischemia was not significantly different between groups. With reperfusion, both Pi and pH values rapidly returned to preischemia values. PCr levels, however, did not recover in hyperglycemic diabetic animals, with the degree of residual impairment dependent on the preischemia glucose level. Results suggest that optimal management of diabetes may lessen the degree of injury within the ischemic penumbra in diabetic patients who suffer a stroke.

Topics: Analysis of Variance; Animals; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 1; Hydrogen-Ion Concentration; Ischemic Attack, Transient; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Phosphorus; Prediabetic State; Prosencephalon; Rats; Rats, Inbred BB; Reperfusion