Xuesi Wan

Attitudes Toward Diabetes Affect Maintenance of Drug-Free Remission in Patients With Newly Diagnosed Type 2 Diabetes After Short-Term Continuous Subcutaneous Insulin Infusion Treatment

OBJECTIVE Short-term intensive insulin treatment in patients with newly diagnosed type 2 diabetes can improve β-cell function and insulin sensitivity, which results in long-term remission without need for further antidiabetes medication. Patient attitudes toward their disease were assessed using the Diabetes Care Profile (DCP) tool to evaluate the potential impact on maintaining long-term remission. RESEARCH DESIGN AND METHODS Newly diagnosed patients with type 2 diabetes were recruited and treated with continuous subcutaneous insulin infusion (CSII) for 2–3 weeks. They were also invited to participate in diabetes self-management intervention during hospitalization and complete a DCP questionnaire on attitudes toward diabetes at baseline and 3, 6, and 12 months after suspension of CSII. RESULTS Near normoglycemia was achieved by 118 patients after short-term CSII, with 65 remaining in drug-free remission for >1 year. They had significantly better glycemic control and greater restoration of acute insulin response after CSII as well as higher educational attainment compared with patients experiencing relapse. They also achieved higher scores in positive attitude, (belief in) importance of care, care ability, self-care adherence, and less negative attitude. Differences between the two groups became greater over time. Cox proportional hazards model analysis indicated that greater self-care adherence (hazard ratio 0.184, P < 0.001) and homeostasis model assessment of insulin resistance before treatment (0.854, P = 0.053) were independent predictors for long-term remission, whereas elevated 2-h postprandial plasma glucose after CSII (1.156, P = 0.015) was a risk factor for relapse. CONCLUSIONS Attitudes toward diabetes affect long-term drug-free remission in newly diagnosed patients with type 2 diabetes after short-term CSII.

Impact of Vitamin D on Chronic Kidney Diseases in Non-Dialysis Patients: A Meta-Analysis of Randomized Controlled Trials

Background and Objectives Recent studies have supported a role for both newer and more established vitamin D compounds in improving proteinuria, although systematic evaluation is lacking. Furthermore, concerns remain regarding the influence of vitamin D on the progression of renal function. We analyzed the efficacy and safety of vitamin D in non-dialysis patients and compared the use of newer versus established vitamin D compounds by performing a meta-analysis of randomized controlled trials. Design A literature search of PubMed (1975 to September, 2012), EMBASE.com (1966 to September, 2012) and Ovid EBM Reviews (through September, 2012) was conducted. Results Eighteen studies were eligible for final inclusion; of these, six explored the effects of vitamin D on proteinuria, twelve studied the effects of supplementation on renal function, and fifteen discussed the incidence of hypercalcemia. Compared to the placebo or no interference, both the newer and established vitamin D sterols reduced proteinuria to a similar extent (RR, 2.00; 95% CI, 1.42 to 2.81). No decrease in the glomerular filter rate was observed (SMD, −0.10; 95%CI, −0.24 to 0.03), and the risk for dialysis initiation was 1.48 (95% CI, 0.54 to 4.03) with vitamin D treatment. Additionally, there was an increased risk of hypercalcemia for patients treated with either newer or established vitamin D compounds as compared with the controls (RR, 4.78; 95% CI, 2.20 to 10.37). The head-to-head studies showed no differences in the effects of either newer or established compounds on proteinuria or the risk of hypercalcemia. No serious adverse events were associated with the administration of vitamin D. Conclusions Vitamin D therapy appears to decrease proteinuria and have no negative influence on renal function in non-dialysis patients. But the occurrence of hypercalcemia should be evaluated when vitamin D is provided. No superiority for newer versus established vitamin D analogue is found.

Short-Term Continuous Subcutaneous Insulin Infusion Combined with Insulin Sensitizers Rosiglitazone, Metformin, or Antioxidant α-Lipoic Acid in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

BACKGROUND Short-term continuous subcutaneous insulin infusion (CSII) in patients with newly diagnosed type 2 diabetes has been proved effective in improving metabolic control and β-cell function, thus inducing long-term drug-free remission. A randomized controlled trial was conducted to investigate whether CSII in combination with rosiglitazone, metformin, or α-lipoic acid separately brings about extra benefits. PATIENTS AND METHODS One hundred sixty patients with newly diagnosed type 2 diabetes were randomized to one of four treatment groups: CSII alone, CSII in combination with rosiglitazone or metformin for 3 months, or CSII with α-lipoic acid intravenous infusion for 2 weeks. Duration of CSII treatment was identical in the four groups. Glucose and lipid profiles, homeostasis model assessment (HOMA) indices, acute insulin response (AIR), intramyocellular lipid (IMCL) level, and malondialdehyde level were compared before and after intervention. RESULTS The near-normoglycemia rate at the third month in CSII alone and that in combination with rosiglitazone, metformin, or α-lipoic acid was 72.5%, 87.5%, 90%, and 75%, respectively (metformin group vs. CSII alone, P=0.045). The metformin group achieved euglycemia in a shorter time (2.6 ± 1.3 vs. 3.7 ± 1.8 days, P=0.020) with less daily insulin dosage and was more powerful in lowering total cholesterol, increasing AIR and HOMA β-cell function, whereas reduction of IMCL in the soleus was more obvious in the rosiglitazone group but not in the metformin group. The efficacy of combination with α-lipoic acid was similar to that of CSII alone. CONCLUSIONS Short-term CSII in combination with rosiglitazone or metformin is superior to CSII alone, yet the efficacy of the two differs in some way, whereas that with α-lipoic acid might not have an additive effect.

Increased 1,5-anhydroglucitol predicts glycemic remission in patients with newly diagnosed type 2 diabetes treated with short-term intensive insulin therapy.

BACKGROUND Short-term intensive insulin therapy has been shown to induce long-term glycemic remission in patients with newly diagnosed type 2 diabetes. However, predictors of remission are still uncertain. This study was conducted to evaluate whether changes of 1,5-anhydroglucitol (1,5AG) and fructosamine (FA) could be a predictor of remission. SUBJECTS AND METHODS Newly diagnosed drug-naive patients with type 2 diabetes (n = 64) were enrolled. After baseline assessments, continuous subcutaneous insulin infusion (CSII) was administered in all patients until euglycemia was achieved and maintained for another 2 weeks. Patients were subsequently followed monthly for 3 months. 1,5AG and FA were measured before and after therapy and at 1-month follow-up. RESULTS After CSII, A1C and FA decreased from baseline, whereas 1,5AG increased. 1,5AG was higher at 1-month follow-up (11.5 ± 4.1 vs. 6.7 ± 2.8 mg/L, P<0.001), whereas FA was lower (273.1 ± 56.1 vs. 316.2 ± 39.3 μmol/L, P = 0.021) in the remission group. Stepwise logistic regression analysis showed that 1,5AG at 1-month follow-up rather than FA was an independent predictor of remission after adjusting for other confounders (odds ratio 1.56, 95% confidence interval [CI] 1.15-2.12, P = 0.004). The area under the curve of the receiver operating characteristic curve analysis was 0.85 (95% CI 0.75-0.96, P<0.001). The optimal cutoff point for 1,5AG at 1-month follow-up was 8.9 mg/L (specificity, 83.3%; sensitivity, 78.6%). CONCLUSIONS Improvement of 1,5AG predicts maintenance of glycemic remission after intensive insulin therapy in patients with newly diagnosed type 2 diabetes.

Adverse effect of metformin therapy on serum vitamin B12 and folate: Short-term treatment causes disadvantages?

Diabetes is a global public health challenge that imposes heavy burdens on communities and individuals. Metformin, the first-line medication for diabetes, has the superiority of reducing risk of macrovascular diseases, all-cause mortality and even possibly cancers. Recent observational studies, however, have demonstrated that long-term metformin therapy increases the probability of vitamin B12 and folate deficiency, and might contribute to the progression of diabetic peripheral neuropathy. Despite metformin is widely used and extensively studied, randomized controlled trials performed to explore the effects of metformin on vitamin B12 and folate are limited. Besides, whether short-term treatment causes vitamin deficiency is a pending issue. We postulate that even a few-month treatment with metformin results in the decrease of vitamin B12 and folate. However, supplementation of vitamin B12 rather than the combination of vitamin B12 and folate might be profitable based on the mechanism of metformin on vitamins in patients with type 2 diabetes. This viewpoint differs from those of majority that a combined supplementation of vitamin B12 and folate is inclined to be advised.

Fufang Xue Shuan Tong capsules inhibit renal oxidative stress markers and indices of nephropathy in diabetic rats

Fufang Xue Shuan Tong (FXST) capsules, a traditional Chinese medicine, have been used to treat diabetic nephropathy for many years. FXST has been shown to attenuate elevated levels of oxidative stress in the retina of diabetic rats. However, whether FXST protects kidneys through the same mechanism(s) remains unclear. In this study, diabetes was induced in rats by administration of a high-fat diet and low-dose streptozotocin. Rats were administered low (450 mg/kg/day), middle (900 mg/kg/day) or high (1800 mg/kg/day) doses of FXST orally for 3 months. Another group was administered 50 mg/kg/day orally for the same period. The results indicated that all doses of FXST reduced urinary protein excretion and creatinine clearance and ameliorated the diabetic nephropathy-related mesangial matrix expansion. However, only middle and high doses of FXST prevented glomerular hypertrophy in diabetic rats, and the high dose showed the greatest inhibitory effect with regard to mesangial matrix expansion. Furthermore, superoxide dismutase activities were significantly elevated, whereas malondialdehyde levels were significantly reduced in the renal cortex following FXST treatment. The kidney-protective role of FXST is not inferior to that of captopril, one of the most commonly used drugs for the treatment of diabetic nephropathy. In conclusion, FXST retards the progression of diabetic nephropathy, while high-dose FXST shows the most prominent effect in counteracting the pathological changes of diabetic nephropathy. The renoprotective action of FXST is induced by the reduction of oxidative stress in diabetic nephropathy.

Insulin requirement profiles of short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes and its association with long-term glycemic remission

AIMS To investigate the insulin requirement profiles during short-term intensive continuous subcutaneous insulin infusion (CSII) in patients with newly diagnosed type 2 diabetes and its relationship with long-term glycemic remission. METHODS CSII was applied in 104 patients with newly diagnosed type 2 diabetes. Daily insulin doses were titrated and recorded to achieve and maintain euglycemia for 2 weeks. Measurements of blood glucose, lipid profiles as well as intravenous glucose tolerance tests were performed before and after the therapy. Afterwards, patients were followed up for 1 year. RESULTS Total daily insulin dose (TDD) was 56.6±16.1IU at the first day when euglycemia was achieved (TDD-1). Thereafter, TDD progressively decreased at a rate of 1.4±1.0IU/day to 36.2±16.5IU at the end of the therapy. TDD-1 could be estimated with body weight, FPG, triglyceride and waist circumference in a multiple linear regression model. Decrement of TDD after euglycemia was achieved (ΔTDD) was associated with reduction of HOMA-IR (r=0.27, P=0.008) but not with improvement in β cell function. Patients in the lower tertile of ΔTDD had a significantly higher risk of hyperglycemia relapse than those in the upper tertile within 1 year (HR 3.4, 95%CI [1.4, 8.4], P=0.008). CONCLUSIONS There is a steady decline of TDD after euglycemia is achieved in patients with newly diagnosed type 2 diabetes treated with CSII, and ΔTDD is associated with a better long-term glycemic outcome.

Angiopoietin-like protein 8/betatrophin correlates with hepatocellular lipid content independent of insulin resistance in non-alcoholic fatty liver disease patients

To explore angiopoietin‐like protein 8 (ANGPTL‐8) levels, and its association with hepatocellular lipid content (HCL) and insulin resistance in patients with different extents of non‐alcoholic fatty liver disease (NAFLD).

Glucose metabolism, insulin sensitivity and β-cell function in type A insulin resistance syndrome around puberty: a 9-year follow-up.

Diabetes mellitus is thought to be progressive. Insufficient insulin secretion in compensation for insulin resistance leads to glucose intolerance. A previously reported proband with type A insulin resistance syndrome and her younger twin brothers with and without the R1174W missense mutation in the insulin receptor gene were followed for 9 years to study the progression of glucose metabolism, insulin sensitivity, and β-cell function around puberty. Five-hour OGTT was performed in them at each visit. Areas under the curves of glucose, insulin and C-peptides, insulinogenic index, AIR, and Homa indices were assessed. Intramyocellular lipids (IMCLs) were quantified in the proband and compared to those of 12 nondiabetic subjects, 118 newly diagnosed type 2 diabetic patients. The proband maintained normal HbA1c (27-37 mmol/mol) and fasting plasma glucose (3.7-4.5 mmol/l), and her glucose tolerance ameliorated over years. The probands Homa-IR decreased into adulthood, while her Homa-B, insulinogenic index, AIR, AUCs of insulin, and C-peptide decreased accordingly. Homa-B to Homa-IR ratios stayed significantly higher than normal. Homa-B, AUCs of insulin, and C-peptide of the twin brothers increased in response to the increment of Homa-IR as they entered middle and late puberty. The changes were more dramatic in the twin brothers carrying the mutation. IMCLs of the proband were lower than those of the nondiabetic counterparts and were disproportional for the degree of insulin resistance. Our longitudinal data of type A insulin resistance syndrome around puberty provide significant information for the study of insulin secretion in compensation for insulin resistance.

Vitamin D and its receptor regulate lipopolysaccharide-induced transforming growth factor-β, angiotensinogen expression and podocytes apoptosis through the nuclear factor-κB pathway.

To investigate the effects of vitamin D and its receptor on cytokines expression and podocytes apoptosis.