Brain Activation During Working Memory Is Altered in Patients With Type 1 Diabetes During Hypoglycemia

OBJECTIVE To investigate the effects of acute hypoglycemia on working memory and brain function in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Using blood oxygen level–dependent (BOLD) functional magnetic resonance imaging during euglycemic (5.0 mmol/L) and hypoglycemic (2.8 mmol/L) hyperinsulinemic clamps, we compared brain activation response to a working-memory task (WMT) in type 1 diabetic subjects (n = 16) with that in age-matched nondiabetic control subjects (n = 16). Behavioral performance was assessed by percent correct responses. RESULTS During euglycemia, the WMT activated the bilateral frontal and parietal cortices, insula, thalamus, and cerebellum in both groups. During hypoglycemia, activation decreased in both groups but remained 80% larger in type 1 diabetic versus control subjects (P < 0.05). In type 1 diabetic subjects, higher HbA1c was associated with lower activation in the right parahippocampal gyrus and amygdala (R2 = 0.45, P < 0.002). Deactivation of the default-mode network (DMN) also was seen in both groups during euglycemia. However, during hypoglycemia, type 1 diabetic patients deactivated the DMN 70% less than control subjects (P < 0.05). Behavioral performance did not differ between glycemic conditions or groups. CONCLUSIONS BOLD activation was increased and deactivation was decreased in type 1 diabetic versus control subjects during hypoglycemia. This higher level of brain activation required by type 1 diabetic subjects to attain the same level of cognitive performance as control subjects suggests reduced cerebral efficiency in type 1 diabetes

Reduced T2* Values in Soleus Muscle of Patients with Type 2 Diabetes Mellitus

Tissue water transverse relaxation times (T2) are highly sensitive to fluid and lipid accumulations in skeletal muscles whereas the related T2* is sensitive to changes in tissue oxygenation in addition to factors affecting T2. Diabetes mellitus (DM) affects muscles of lower extremities progressively by impairing blood flow at the macrovascular and microvascular levels. This study is to investigate whether T2 and T2* are sensitive enough to detect abnormalities in skeletal muscles of diabetic patients in the resting state. T2 and T2* values in calf muscle of 18 patients with type 2 DM (T2DM), 22 young healthy controls (YHC), and 7 age-matched older healthy controls (OHC) were measured at 3T using multi-TE spin echo and gradient echo sequences. Regional lipid levels of the soleus muscle were also measured using the Dixon method in a subset of the subjects. Correlations between T2, T2*, lipid levels, glycated hemoglobin (HbA1c) and presence of diabetes were evaluated. We found that T2 values were significantly higher in calf muscles of T2DM subjects, as were T2* values in anterior tibialis, and gastrocnemius muscles of T2DM participants. However, soleus T2* values of the T2DM subjects were significantly lower than those of the older, age-matched HC cohort $(22.9\pm 0.5 vs 26.7\pm 0.4 ms, p<0.01)$. The soleus T2* values in the T2DM cohort were inversely correlated with the presence of diabetes (t = −3.46, p<0.001) and with an increase in HbA1c, but not with body mass index or regional lipid levels. Although multiple factors may contribute to changes in T2* values, the lowered T2* value observed in the T2DM soleus muscle is most consistent with a combination of high oxygen consumption and poor regional perfusion. This finding is consistent with results of previous perfusion studies and suggests that the soleus in individuals with T2DM is likely under tissue oxygenation stress

Dapagliflozin Saxagliptin Insulin Study

Simonson DC, Testa MA, Ekholm E, Su M, Vilsboll T, Jabbour S, Lind M. Continuous Glucose Monitoring Profiles and Health Outcomes after Dapagliflozin Plus Saxagliptin vs Insulin Glargine. Journal of Clinical Endocrinology and Metabolism Supplementary Figure