Effect of Diacerein on Insulin Secretion and Metabolic Control in Drug-Naïve Patients With Type 2 Diabetes: A randomized clinical trial

OBJECTIVE - To assess the effect of diacerein on insulin secretion and metabolic control in drug-naïve patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - A randomized, double-blind, placebo-controlled clinical trial was carried out in 40 drug-naïve adult patients with type 2 diabetes. A metabolic profile including interleukin (IL)-1β, tumor necrosis factor-a, IL-6, and fasting insulin levelswas carried out before the intervention and 2months afterward. A hyperglycemic-hyperinsulinemic clamp technique was performed to assess the phases of insulin secretion and insulin sensitivity. After randomization, 20 patients received diacerein (50mg once daily) for the first 15 days and twice daily for 45 additional days. The remaining patients received placebo. Intra- and intergroup differences were calculated by Wilcoxon signed rank and Mann-Whitney U tests. RESULTS-Therewere significant increases in first (102 ± 63 vs. 130 ± 75 pmol/L; P<0.01), late (219 ± 111 vs. 280 ± 135 pmol/L; P<0.01), and total insulin (178691 vs. 216699pmol/L; P<0.01) secretionswithout changes in insulin sensitivity after diacerein administration. There were significant decreases in fasting glucose (7.9 ± 1.4 vs. 6.8 ± 1.0mmol/L; P<0.01) and in A1C levels (8.3 ± 1.0 vs. 7.0 ± 0.8%; P < 0.001) after diacerein administration. There were no significant changes after placebo administration in the above-mentioned evaluations. CONCLUSIONS - Insulin secretion increased and metabolic control improved after diacerein administration in drug-naïve patients with type 2 diabetes. © 2011 by the American Diabetes Association

The Targeting of Plasmalemmal Ceramide to Mitochondria during Apoptosis

Ceramide is a key lipid mediator of cellular processes such as differentiation, proliferation, growth arrest and apoptosis. During apoptosis, ceramide is produced within the plasma membrane. Although recent data suggest that the generation of intracellular ceramide increases mitochondrial permeability, the source of mitochondrial ceramide remains unknown. Here, we determine whether a stress-mediated plasmalemmal pool of ceramide might become available to the mitochondria of apoptotic cells. We have previously established annexin A1—a member of a family of Ca2+ and membrane-binding proteins—to be a marker of ceramide platforms. Using fluorescently tagged annexin A1, we show that, upon its generation within the plasma membrane, ceramide self-associates into platforms that subsequently invaginate and fuse with mitochondria. An accumulation of ceramide within the mitochondria of apoptotic cells was also confirmed using a ceramide-specific antibody. Electron microscopic tomography confirmed that upon the formation of ceramide platforms, the invaginated regions of the plasma membrane extend deep into the cytoplasm forming direct physical contacts with mitochondrial outer membranes. Ceramide might thus be directly transferred from the plasma membrane to the mitochondrial outer membrane. It is conceivable that this “kiss-of-death” increases the permeability of the mitochondrial outer membrane thereby triggering apoptosis

Hyperinsulinemia in glucose-tolerant women with preeclampsia A controlled study

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Maternal effect of Type 2 diabetes mellitus on insulin sensitivity and metabolic profile in healthy young Mexicans

The objective of this study was to identify the maternal effect of Type 2 diabetes mellitus (T2DM) on insulin sensitivity and metabolic profiles of young healthy, Mexican people (n = 15). A cross-sectional study was performed in these subjects with a family history of T2DM in both first and second degree relatives on the maternal side and 15 control subjects. The following tests were carried out: insulin tolerance test and metabolic profile. Systolic blood pressure and serum uric acid were significantly higher in probands than controls. Insulin sensitivity was not different between either group studied (4.7 ± 0.9 in probands vs 4.5 ± 0.8%/min in controls; p = 0.52). In conclusion: family history of T2DM on the maternal side increased both systolic blood pressure and serum uric acid level in probands, without modification in their insulin sensitivity. Triglycerides concentration had a tendency to be higher in probands than controls

Maternal effect of Type 2 diabetes mellitus on insulin sensitivity and metabolic profile in healthy young Mexicans

The objective of this study was to identify the maternal effect of Type 2 diabetes mellitus (T2DM) on insulin sensitivity and metabolic profiles of young healthy, Mexican people (n = 15). A cross-sectional study was performed in these subjects with a family history of T2DM in both first and second degree relatives on the maternal side and 15 control subjects. The following tests were carried out: insulin tolerance test and metabolic profile. Systolic blood pressure and serum uric acid were significantly higher in probands than controls. Insulin sensitivity was not different between either group studied (4.7 +/- 0.9 in probands vs 4.5 +/- 0.8%/min in controls; p = 0.52). In conclusion: family history of T2DM on the maternal side increased both systolic blood pressure and serum uric acid level in probands, without modification in their insulin sensitivity. Triglycerides concentration had a tendency to be higher in probands than controls

Acute effect of physiologic hyperinsulinaemia on serum leptin concentration in healthy young people

This study aimed to identify the acute effect of a physiologic dose of insulin, enough to produce hyperinsulinaemia similar to that obtained in the postprandial state, on serum lepfin concentrations in healthy young people. A randomised, single blind controlled clinical trial was performed in 45 healthy, non-obese, young volunteers. Serum leptin concentration, uric acid, creatinine levels and lipid profile were determined for all subjects. Insulin suppression test modified with octreotide, used to produce physiologic hyperinsulinaemia, or saline infusion as control, were performed. Steady state insulin (SSI) concentrations were calculated and they represented the hyperinsulinaemia state. Clinical characteristics and laboratory profiles were similar between groups. There was no significant difference between the effect of insulin or saline infusions on the serum leptin concentration. The acute effect of physiologic hyperinsulinaemia did not modify the serum leptin concentration in healthy young people

Comparison of homeostasis model analysis with insulin tolerance test in the assessment of insulin resistance in healthy young people

The aim of this paper was to compare homeostasis model analysis and insulin tolerance test in the assessment of insulin resistance in healthy young people. A cross-sectional study was carried out in 129 healthy non-obese young volunteers. Fasting glucose and serum insulin were measured, homeostasis model analysis calculated and an insulin tolerance test performed. The constant for the rate of serum glucose disappearance calculated with insulin tolerance test was of 4.7 � 0.9%/min and insulin resistance obtained with homeostasis model analysis was of 1.8 � 0.9. Results did not show significant correlation between homeostasis model analysis and insulin tolerance test in the estimation of insulin resistance. In conclusion, the assessment of insulin resistance with homeostasis model analysis was not comparable to that obtained with insulin tolerance test in healthy young people. However, we recommend the use of ITT as a method for estimating insulin resistance in healthy people based on the particular characteristics of this technique

Effect of Fucoidan administration on insulin secretion and insulin resistance in overweight or obese adults

The aim of this article is to evaluate the effect of fucoidan administration on insulin secretion and insulin sensitivity in overweight or obese adults. A randomized, double-blind, placebo-controlled clinical trial was carried out in 25 obese or overweight volunteers. Thirteen patients received an oral dose of 500mg of fucoidan once daily before breakfast and 12 patients received placebo for 3 months. Before and after the intervention, fasting glucose and 2-h postload, total cholesterol, high-density lipoprotein cholesterol, triglycerides, and insulin levels were measured. Low-density lipoprotein cholesterol (LDL-C) and homeostasis model analysis formulas (HOMA) for ?-cell function and insulin resistance were calculated. The results showed a significant decrease in diastolic blood pressure (71.7�12.2 vs. 67.8�13.8mmHg; P<.05) and LDL-C (3.1�0.5 vs. 2.7�0.6mmol/l; P<.01) with increase in insulin levels (60.6�24.0 vs. 78.6�32.4pmol/l; P<.05), HOMA ?-cell (35.0�20.8 vs. 50.6�18.7; P<.05) and HOMA IR (1.9�1.2 vs. 2.6�1.8; P<.05) were observed after fucoidan administration. We conclude that fucoidan administration during a 3-month period in overweight or obese adults decreased diastolic blood pressure and LDL-C concentrations, increasing insulin secretion and insulin resistance. � 2014 Mary Ann Liebert, Inc

A new model to fit glucose concentration during the insulin tolerance test improving the predictive capability to estimate insulin sensitivity [1]

[No abstract available