Insulin resistance is present in European non-diabetic relatives of Type 2 diabetic patients. The insulin resistance is independent of degree of obesity and is restricted solely to the pathway of non-oxidative glucose metabolism. Diabet. Med. 18, 533-540 (2001)

With the aim of investigating glucose-mediated glucose disposal (glucose effectiveness [GE]) in 15 (3 female and 12 male subjects) insulin-resistant normoglycemic relatives of patients with type 2 diabetes (DM2), and 15 age-, sex-, and BMI-matched control subjects without a family history of DM2, we performed 2 studies: 1) a 5-h euglycemic near-normoinsulinemic pancreatic clamp with somatostatin (360 µg/h), insulin (0.25 mU · kg -1 · min -1 ), glucagon (0.5 ng · kg -1 · min -1 ), growth hormone (6 ng · kg -1 · min -1 ), and tritiated glucose infusion and indirect calorimetry; and 2) on a separate day, an identical 5-h clamp but at hyperglycemia (~12 mmol/l) over the last 2 h. Fasting plasma insulin (PI) concentrations were elevated in the relatives compared with control subjects (49 ± 6 vs. 32 ± 5 pmol/l, P < 0.04), whereas plasma glucose (PG) was not (5.6 ± 0.1 vs. 5. (1), and several studies have demonstrated decreased insulin sensitivity (2-6), impaired activation of muscle glycogen synthase by insulin (5,6), and subtle defects of insulin secretion (2,4,7) in such subjects. Most recently, we demonstrated increased glucosemediated glucose disposal at basal insulin in insulin-resistant normoglycemic first-degree relatives of patients with DM2 (2), using the Bergman minimal model (8). From the latter study, we hypothesized that the increase in glucose sensitivity (S g ) might be a novel compensatory mechanism by which these relatives maintain normal glucose tolerance (2). This scenario was consistent with an earlier large-scale longitudinal follow-up study in normoglycemic relatives of 2 parents with DM2 in whom a decreased S g and decreased insulin sensitivity (S i ) both predicted an increased risk of future development of diabetes (9). In contrast, Doi et al. (10) noted a decreased S g with normal S i and decreased first-phase insulin secretion in normoglycemic relatives of Japanese DM2 patients. However, the estimation of S g may be influenced by the extent of the acute insulin secretory response, i.e., the lower the first-phase insulin response, the lower the S g (11-13). Concern has also been expressed as to whether the minimal model technique using unlabeled glucose accurately measures S g (14,15).Glucose-mediated glucose disposal is an important factor controlling glucose tolerance (16,17), but which metabolic pathways are involved is uncertain (18)(19)(20). Acute hyperglycemia itself is known to enhance peripheral glucose uptake (19-24) associated with enhanced glucose oxidation and gluFrom the Diabetes Research Centre

Moderate but clinically obtainable improvement of metabolic control in patients with type 1 diabetes seems to reduce the loss of Mg, increase serum HDL cholesterol, and decrease serum triglycerides. The decrease in serum triglycerides was associated with the change in serum total Mg concentration. These reductions in Mg loss and serum triglycerides might reduce the risk of developing cardiovascular disease in patients with type 1 diabetes.

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Background [18F]-fluorodeoxyglucose-positron emission tomography / computed tomography ([18F]FDG-PET/CT) has been implemented sporadically in hospital settings as the standard of care examination for recurrent breast cancer. We aimed to explore the clinical impact of implementing [18F]FDG-PET/CT for patients with clinically suspected recurrent breast cancer and validate the diagnostic accuracy. Methods Women with suspected distant recurrent breast cancer were prospectively enrolled in the study between September 2017 and August 2019. [18F]FDG-PET/CT was performed, and the appearance of incidental benign and malignant findings was registered. Additional examinations, complications, and the final diagnosis were registered to reflect the clinical consequence of such findings. The diagnostic accuracy of [18F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard. Results [18F]FDG-PET/CT reported breast cancer metastases in 72 of 225 women (32.0%), and metastases were verified by biopsy in 52 (52/225, 23.1%). Prior probability and posterior probability of a positive test for suspected metastatic cancer and incidental malignancies were 27%/85% and 4%/20%, respectively. Suspected malignant incidental findings were reported in 46 patients (46/225, 20.4%), leading to further examinations and final detection of nine synchronous cancers (9/225, 4.0%). These cancers originated from the lung, thyroid, skin, pancreas, peritoneum, breast, kidney, one was malignant melanoma, and one was hematological cancer. False-positive incidental malignant findings were examined in 37/225 patients (16.4%), mainly in the colon (n = 12) and thyroid gland (n = 12). Ten incidental findings suspicious for benign disease were suggested by [18F]FDG-PET/CT, and further examinations resulted in the detection of three benign conditions requiring treatment. Sensitivity, specificity, and AUC-ROC for diagnosing distant metastases were 1.00 (0.93-1.0), 0.88 (0.82-0.92), and 0.98 (95% CI 0.97-0.99), respectively.Conclusion [18F]FDG-PET/CT provided a high posterior probability of positive test, and a negative test was able to rule out distant metastases in women with clinically suspected recurrent breast cancer. One-fifth of patients examined for incidental findings detected on [18F]FDG-PET/CT were diagnosed with clinically relevant conditions. Further examinations of false-positive incidental findings in one of six women should be weighed against the high accuracy for diagnosing metastatic breast cancer.Trial registration: Clinical.Trials.gov. NCT03358589. Registered 30 November 2017 - Retrospectively registered, http://www.ClinicalTrials.gov