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Background: The objective of this study was to assess the feasibility of using blood spots collected by finger sticks and dried on filter paper for measuring Hemoglobin A1c (HbA1c) by a new method to assess long term glycemic control. Blood spots offer advantages of short collection time, low invasiveness, reduction of sample volume, ability to obtain repeated measures and ease of sample storage. Methods: Forty subjects contributed a blood spot sample from a finger stick and a blood sample through venipuncture. The blood spots obtained from finger sticks on a filter paper were air-dried for 4 hours at room temperature after collection. Using an automated dried blood spot (DBS) puncher, 6.0 mm blood disks were obtained for testing and rehydrated in assay buffer. All samples were tested in parallel. Samples were evaluated for the presence of HbA1C using conventional commercial kits based on an immuno-turbidimetric assay in whole blood modified for use in dried blood spots. Results: A positive correlation (R²= 0.93) was found in HbA1c levels from the blood spot and whole blood samples. The HbA1c levels obtained from blood spots (5.41 ± 1.06%; Assay range 3.36%- 12.02%) were similar to those derived from whole blood samples (5.44 ± 1.68%; Assay range 4.92%-12.29%). The extracted samples showed good stability for 8 days when stored at 4°C. The between assay CV ranged between 5.25%- 14.79% and the within run variation was between 4.28%- 10.33%. Conclusion: We conclude that in our assay, HbA1c levels obtained from blood spot samples correlate well with values obtained from standard whole blood assays. The design of the assay and nature of the samples also make this method suitable for screening programs that consist of self-sampling for better management of chronic glycemia and its complications. [ABSTRACT FROM AUTHOR]

Intensive IV insulin therapy is currently recommended for the treatment of hyperglycemia in the surgical intensive care unit (SICU). We conducted a prospective randomized clinical trial to compare 2 protocols for titration of IV insulin in patients after cardiovascular or Wansplant surgery. We used the Glucommander, a computer-based algorithm, vs. a paper protocol adapted from the University of Leuven ICU. 93 patients (Paper n=46 and Glucommander n=47) with a mean age of 60 (20-90) were enrolled prior to cardiovascular or transplant surgery. 43% had a prior history of diabetes. The specific surgeries were: 28 patients-renal transplant for end stage renal disease (ESRD), 3 patients- liver transplant, 41 patients- coronary bypass, 17 patients- valve replacement and 4 patients-aneurysm repair. All patients were begun on IV insulin infusion when post-operative blood glucose (BG) was > 120 mg/dl. Both protocols call for hourly bedside testing of BG and IV insulin titration. BG target range was 80-120 mg/dl. We compared BG control achieved in the SICU for up to 200 hours. The median duration of IV insulin therapy was the same for both groups: 21 hours (3-200). The median time to reach the target range for BG was 5.2 hours-paper protocol and 4.1 hours-Glucommander protocol p=.06. The percentage of total BG readings in the target range was 48% for paper and 58% for Glucommander p=.009. The overall percentage of hypoglycemia (BG readings.< 60 mg/dl) was: paper-l.7% of all readings and Glucommander- 1.1% of all readings. Of these only 0.2% of all readings in each group were less than 50 mg/dl. However the percentage of BG readings< 60 mg/dl was higher, 2.3%, in the transplant group (90% ESRD) as compared with 1.0% in the cardiovascular group (8% ESRD). The percentage of BG readings < 60 mg/dl in the subset of 31 transplant patients was greater with paper 3.6% vs. Glucommander 0.8% p=.05. The mean frequency of BG testing was similar: every 1.4 hours with paper vs. 1.1 hours with Glucommander. In conclusion the Glucommander achieves a BG of 80-120 mg/dl somewhat faster and maintains BG in this target range significantly better than our paper protocol. Additionally the Glucommander was associated with less hypoglycemia especially in a population of patients with ESRD who are at the highest risk for hypoglycemia while treated with IV insulin. It is possible that the Glucommander and other computerized protocols will be able to achieve similar improved glycemic outcomes in other inpatient populations. [ABSTRACT FROM AUTHOR]

Glucose-6-phosphatase (G6Pase) is a multicomponent system located in the endoplasmic reticulum comprising a catalytic subunit and transporters for glucose-6-phosphate, inorganic phosphate, and glucose. We have recently cloned a novel gene that encodes an islet-specific G6Pase catalytic subunit-related protein (IGRP) (Ebert et al., Diabetes 48:543-551, 1999). To begin to investigate the molecular basis for the islet-specific expression of the IGRP gene, a series of truncated IGRP-chloramphenicol acetyltransferase (CAT) fusion genes were transiently transfected into the islet-derived mouse betaTC-3 and hamster insulinoma tumor cell lines. In both cell lines, basal fusion gene expression decreased upon progressive deletion of the IGRP promoter sequence between -306 and -66, indicating that multiple promoter regions are required for maximal IGRP-CAT expression. The ligation-mediated polymerase chain reaction footprinting technique was then used to compare trans-acting factor binding to the IGRP promoter in situ in betaTC-3 cells, which express the endogenous IGRP gene, and adrenocortical Y1 cells, which do not. Multiple trans-acting factor binding sites were selectively identified in betaTC-3 cells that correlate with regions of the IGRP promoter identified as being required for basal IGRP-CAT fusion gene expression. The data suggest that hepatocyte nuclear factor 3 may be important for basal IGRP gene expression, as it is for glucagon, GLUT2, and Pdx-1 gene expression. In addition, binding sites for several trans-acting factors not previously associated with islet gene expression, as well as binding sites for potentially novel proteins, were identified. [ABSTRACT FROM AUTHOR]

Analyses by anion exchange chromatography indicate that heparan sulfate proteoglycans isolated from the livers of experimentally diabetic rats have a reduced net negative charge as compared with heparan sulfate proteoglycans from control rats. In contrast, the size of the normal and diabetic proteoglycans are indistinguishable as are the size of individual polysaccharide chains when compared by gel chromatography. The reduced net negative charge of heparin sulfate from diabetic rats is shown to be caused by a reduced number of sulfate groups present in the diabetic heparan sulfate. Results are presented suggesting that one of the biosynthetic enzymes; the N-deacelylase, which tentatively has been identified as a regulatory enzyme affecting the sulfate content of the polysaccharide chains, may be inhibited in the diabetic rat.

The article discusses that the representative immunoblot images in the above-cited paper may have been duplicated, authors Iria Nieto-Vázquez and Sonia Fernández-Veledo have decided to voluntarily retract the article.

This article discusses the relationship between the gut microbiota and type 2 diabetes. While research has shown that there are differences in the gut microbiota between individuals with and without diabetes, there is still much to be understood about this complex area of biology. The article highlights the interest in this topic and its potential impact on clinical medicine. The authors also mention a partnership with the Novo Nordisk Foundation to fund further research and expert forums on key topics related to diabetes. The article concludes by stating that the goal of these initiatives is to advance the understanding and treatment of diabetes. [Extracted from the article]

Evaluation of insulin secretory capacity is essential to understand the pathophysiologic condition of individuals with diabetes and assess the efficacy of drugs used in the treatment of this disease. The 1-mg i.v. glucagon stimulation test (GST) is widely used to evaluate residual β-cell function; we previously reported that GST assessment of insulin secretory capacity is useful in assessing the efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs). However, recent reports have indicated that pharmacologic concentrations of glucagon stimulate insulin secretion through GLP-1 receptors, confounding the issue. The current studies were undertaken to reassess the reliability of the GST for evaluation of insulin secretory capacity under GLP-1RAs and dipeptidyl peptidase 4 inhibitors (DPP-4is). Our first study included individuals receiving GLP-1RA treatment, evaluated by the GST before and after treatment. Although the fasting C-peptide response (CPR) levels were elevated after treatment, the induction of insulin secretion by glucagon was significantly reduced. Our second study compared glucagon-induced insulin secretion between DPP-4i users and nonusers, assessed by the GST after propensity score matching. Although the fasting CPR levels were similar in the two investigations, glucagon-induced insulin secretion was significantly lower with DPP-4i use. These results suggest that the GST might underestimate insulin secretory capacity under incretin-based therapy. Article Highlights: The current studies were undertaken to reassess the reliability of the 1-mg i.v. glucagon stimulation test (GST) for evaluation of insulin secretory capacity under glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) and dipeptidyl peptidase 4 inhibitors (DPP-4is). We aimed to determine whether the amount of insulin secretion induced by pharmacologic glucagon stimulation is reduced under these incretin-based therapies, because they both act through GLP-1 receptors. We found that GLP-1RA and DPP-4i treatments significantly reduced insulin secretion on the GST. The GST underestimates insulin secretory capacity under incretin-based therapy by a novel regulatory system of glucagon and GLP-1 signaling in β-cells. [ABSTRACT FROM AUTHOR]

Muscle sn -1,2-diacylglycerol (DAG) and C18:0 ceramide accumulation in sarcolemmal and mitochondrial compartments have been proposed to regulate muscle insulin sensitivity. Here, we evaluated whether weight loss-induced improvements in insulin sensitivity were associated with changes in muscle sn -1,2-DAG and ceramide content in people with obesity and type 2 diabetes. We measured skeletal muscle insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose tracer infusion, and skeletal muscle sn -1,2-DAG and ceramide contents by using liquid chromatography–tandem mass spectrometry after subcellular fractionation and DAG isomer separation in 14 adults with obesity and type 2 diabetes before and after marked (18.6 ± 2.1%) weight loss. Whole-body insulin sensitivity doubled after weight loss. Sarcolemmal sn -1,2-DAG and C18:0 ceramide contents after weight loss were not different from values before weight loss. In contrast, mitochondrial-endoplasmic reticulum (ER) C18:0 ceramide content decreased by ∼20% after weight loss (from 2.16 ± 0.08 to 1.71 ± 0.13 nmol/g, P < 0.005). These results suggest a decrease in muscle mitochondrial-ER C18:0 ceramide content could contribute to the beneficial effect of weight loss on skeletal muscle insulin sensitivity. Article Highlights: Importance of changes in muscle sn -1,2-diacylglycerols (DAG) or C18:0 ceramide in mediating the beneficial effects of weight loss on muscle insulin sensitivity in people is not known. We examined whether weight loss–induced increases in muscle insulin sensitivity in people with obesity and type 2 diabetes are accompanied by changes in muscle sn -1,2-DAG or C18:0 ceramide. Weight loss improved muscle insulin sensitivity, which was accompanied by a 20% decrease in mitochondrial–endoplasmic reticulum C18:0 ceramide without a change in sarcolemmal C18:0 ceramide or sn -1,2-DAG. These results suggest that decreased muscle mitochondrial–endoplasmic reticulum C18:0 ceramide content contributes to the beneficial effect of weight loss on muscle insulin sensitivity. [ABSTRACT FROM AUTHOR]