[Show abstract][Hide abstract] ABSTRACT: Long-standing type 1 diabetes is associated with deficits on neurocognitive testing that suggest central white matter dysfunction. This study investigated whether diffusion tensor imaging (DTI), a type of magnetic resonance imaging that measures white matter integrity quantitatively, could identify white matter microstructural deficits in patients with long-standing type 1 diabetes and whether these differences would be associated with deficits found by neurocognitive tests.
Twenty-five subjects with type 1 diabetes for at least 15 years and 25 age- and sex-matched control subjects completed DTI on a 3.0 Tesla scanner and a battery of neurocognitive tests. Fractional anisotropy was calculated for the major white matter tracts of the brain.
Diabetic subjects had significantly lower mean fractional anisotropy than control subjects in the posterior corona radiata and the optic radiation (P < 0.002). In type 1 diabetic subjects, reduced fractional anisotropy correlated with poorer performance on the copy portion of the Rey-Osterreith Complex Figure Drawing Test and the Grooved Peg Board Test, both of which are believed to assess white matter function. Reduced fractional anisotropy also correlated with duration of diabetes and increased A1C. A history of severe hypoglycemia did not correlate with fractional anisotropy.
DTI can detect white matter microstructural deficits in subjects with long-standing type 1 diabetes. These deficits correlate with poorer performance on selected neurocognitive tests of white matter function.
[Show abstract][Hide abstract] ABSTRACT: Mechanisms responsible for hypoglycemia unawareness remain unknown. Previously, we found that patients with type 1 diabetes and hypoglycemia unawareness had increased brain glucose concentrations as measured by (1)H-magnetic resonance spectroscopy (MRS) compared with controls measured under the same metabolic condition, suggesting that an alteration in brain glucose transport and/or metabolism may play a role in the pathogenesis of hypoglycemia unawareness. To determine whether the brain glucose concentration is altered in normal subjects subjected to recurrent hypoglycemia, we compared the brain glucose concentrations measured in healthy subjects after three episodes of hypoglycemia to blunt the counterregulatory response over 24 hr and compared this value with that measured at a time remote from the antecedent hypoglycemia protocol. Sixteen subjects (9 M/7 F, age 36 +/- 10 years, mean +/- SD) underwent three hypoglycemic clamps for 30 min at 8 AM (0 hr), 5 PM (9 hr), and 7 AM (24 hr). After the third hypoglycemic clamp, subjects underwent a hyperglycemic clamp during which brain glucose concentration was measured by MRS at 4 T. Brain glucose concentration after repeated hypoglycemia was not different from the brain glucose concentration measured in the same subjects during a control study (5.1 +/- 0.8 vs. 4.5 +/- 0.5 mumol/g wet weight, respectively, P = 0.05). These observations suggest that brain glucose transport or metabolism is not altered following short episodes of recurrent hypoglycemia in healthy human volunteers.
Preview · Article · Nov 2005 · Journal of Neuroscience Research
[Show abstract][Hide abstract] ABSTRACT: Hyperglycemia and diabetes alter the function and metabolism of many tissues. The effect on the brain remains poorly defined, but some animal data suggest that chronic hyperglycemia reduces rates of brain glucose transport and/or metabolism. To address this question in human beings, we measured glucose in the occipital cortex of patients with poorly controlled diabetes and healthy volunteers at the same levels of plasma glucose using proton magnetic resonance spectroscopy. Fourteen patients with poorly controlled diabetes (hemoglobin A 1c = 9.8% +/- 1.7%, mean +/- SD) and 14 healthy volunteers similar with respect to age, sex, and body mass index were studied at a plasma glucose of 300 mg/dL. Brain glucose concentrations of patients with poorly controlled diabetes were lower but not statistically different from those of control subjects (4.7 +/- 0.9 vs 5.3 +/- 1.1 micromol/g wet wt; P = .1). Our sample size gave 80% power to detect a difference as small as 1.1 micromol/g wet wt. We conclude that chronic hyperglycemia in diabetes does not alter brain glucose concentrations in human subjects.
[Show abstract][Hide abstract] ABSTRACT: Although it is well established that recurrent hypoglycemia leads to hypoglycemia unawareness, the mechanisms responsible for this are unknown. One hypothesis is that recurrent hypoglycemia alters brain glucose transport or metabolism. We measured steady-state brain glucose concentrations during a glucose clamp to determine whether subjects with type 1 diabetes and hypoglycemia unawareness may have altered cerebral glucose transport or metabolism after exposure to recurrent hypoglycemia. We compared 14 subjects with diabetes and hypoglycemia unawareness to 27 healthy control subjects. Brain glucose concentrations were measured under similar metabolic conditions using in vivo (1)H nuclear magnetic resonance (NMR) spectroscopy at 4 Tesla during a hyperglycemic clamp (plasma glucose = 16.7 mmol/l) with somatostatin and insulin. Subjects with type 1 diabetes and hypoglycemia unawareness had significantly higher brain glucose concentrations compared to that in controls under the same conditions (5.5 +/- 0.3 vs. 4.7 +/- 0.1 micromol/g wet weight, P = 0.016). These data suggest that changes in brain glucose transport or metabolism may occur as a result of recurrent hypoglycemia.
Preview · Article · Jan 2005 · Journal of Neuroscience Research