Risk Factor Analysis for Type 2 Diabetes Patients About Hypoglycemia Using Continuous Glucose Monitoring: Results from a Prospective Observational Study.

Introduction: To determine the relationship between hypoglycemia and glucose variability in outpatients with type 2 diabetes mellitus (T2DM). Materials and Methods: The study participants were 999 outpatients with T2DM who used the FreeStyle Libre Pro for continuous glucose monitoring (FLP-CGM). Hypoglycemia was defined as glucose level of <3.0 mM, and the frequency of episodes and duration of hypoglycemia were evaluated by comparing patients who did or did not achieve time-below-range <3.0 mM (TBR<3.0) of <1% of the time. The association of TBR<3.0 and long% coefficient of variation (%CV) with medications used was examined using multivariate analysis with a proportional odds model. Results: The average TBR<3.0 was 0.33% (4.75 min). The TBR<3.0 >1% group comprised 71/999 patients. Patients of the TBR<3.0 >1% group had lower body mass index, longer disease duration, and poorer renal function. For the TBR<3.0 >1% group, the predicted cutoff values were 7.19 mM average glucose (AG), and 30.30% for %CV. When AG <7.19 mM and %CV >30.30% were considered as hypoglycemic risk factors, the frequency and duration of hypoglycemia increased as the risk factor values increased. In multivariate analysis, sulfonylurea (SU) use, insulin use, and low blood glucose index correlated significantly with increased length of TBR<3.0 and %CV, even after adjustment for concomitant diabetes medications. Conclusion: In T2DM, maintaining TBR<3.0 <1% requires to keep AG >7.2 mM and %CV <30%, in addition to comprehensive management of CGM metrics. Since SU and insulin use is associated with prolonged TBR<3.0 and increased %CV, their doses should be adjusted to avoid excessive fall in AG and raising %CV.

Efficacy of combination of Ezetimibe 10 mg and rosuvastatin 2.5 mg versus rosuvastatin 5 mg monotherapy for hypercholesterolemia in patients with type 2 diabetes.

BACKGROUND: Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus, but many of these patients fail to achieve the target LDL-C level. Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin. However, in patients with type 2 diabetes who are already being treated with satins, it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose. Therefore, this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins. METHODS: The subjects were type 2 diabetic patients under treatment with rosuvastatin (2.5 mg daily), who had LDL-C levels ≥80 mg/dL. They were randomly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day (combination group, n = 40) or an increase of the rosuvastatin dose to 5 mg/day (dose escalation group, n = 39). These two groups were compared at baseline and after 12 weeks of treatment. RESULTS: The percent change of LDL-C was -31% in the combination group and -12% in the dose escalation group. Both groups showed a significant decrease, but the decrease was greater in the combination group. In both groups, there was a significant decrease in the levels of small dense LDL-C, oxidized LDL and remnant-like lipoprotein cholesterol. For all of these parameters, the percent changes were greater in the combination group. Only the combination group showed a significant decrease of triglycerides. Multivariate analysis was performed to identify factors associated with reaching an LDL-C level <80 mg/dL. As a result, add-on therapy with ezetimibe was extracted as a factor related to improvement of LDL-C. CONCLUSIONS: Compared with increasing the dose of rosuvastatin, the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients, suggesting that this combination could suppress the progression of atherosclerosis. TRIAL REGISTRATION: UMIN000011005.

Effects of raloxifene on lipid and bone metabolism in postmenopausal women with type 2 diabetes.

Evidence suggests that bone quality is poorer and fracture risk is higher in patients with diabetes, even those with normal bone mineral density. The aim of this study was to determine the effects of raloxifene on lipid, bone, and glucose metabolism in postmenopausal women with type 2 diabetes. The study subjects (144 postmenopausal women aged less than 80 years with type 2 diabetes) were randomly assigned into three groups: no medication, alfacalcidol 1 µg/day, or raloxifene hydrochloride 60 mg/day. The primary endpoint was the change in LDL-C at 6 months. Raloxifene significantly decreased the levels of bone metabolism markers NTX and BAP at 6 months in patients with diabetes. The primary endpoint, LDL-C at 6 months, was significantly lower in the raloxifene group than in the other two groups. However, percent changes in HDL-C were not significantly different among the three groups. Although glucose metabolism was unaffected, homocysteine, a bone quality marker, was significantly decreased at 6 months in the raloxifene group. The percent improvement in LDL-C did not correlate with percent improvement in any bone metabolism or bone quality markers. Raloxifene, unlike estrogen, improved LDL-C and decreased homocysteine, indicating that raloxifene can potentially improve LDL-C as well as bone quality in postmenopausal women with type 2 diabetes.

Successful treatment of osteomalacia caused by renal tubular acidosis associated with Sjögren's syndrome.

A 62-year-old woman was diagnosed with severe osteomalacia caused by renal tubular acidosis associated with Sjögren's syndrome. She was treated with sodium bicarbonate, risedronate, alfacalcidol, and prednisolone (1 mg/kg). By 24 months, renal tubular acidosis was improved and the bone density had normalized. Here we report the successful amelioration of bone lesions through a multidisciplinary approach that improved renal tubular acidosis, with a special focus on treatment of the underlying inflammatory disorder with glucocorticoids.