A. Avignon

Nonfasting Plasma Glucose is a Better Marker of Diabetic Control Than Fasting Plasma Glucose in Type 2 Diabetes

OBJECTIVE To evaluate the relative value of plasma glucose (PG) at different time points in assessing glucose control of type 2 diabetic patients. RESEARCH DESIGN AND METHODS Glycemic profiles, i.e., PG at prebreakfast (8:00 A.M.), prelunch (11:00 A.M.), postlunch (2:00 P.M.), and extended postlunch (5:00 P.M.) times over the same day, were obtained in 66 type 2 diabetic patients on an ambulatory basis. The different time points of PG were compared with a measurement of HbA1c made in a reference laboratory. RESULTS Extended postlunch PG was lower than prebreakfast PG (104 ± 21 vs. 133 ± 35 mg/dl, P < 0.02) in patients demonstrating good diabetic control (HbA1c ≤ 7.0%), was not different from prebreakfast PG (149 ± 47 vs. 166 ± 26 mg/dl, NS) in patients demonstrating fair diabetic control (7.0% < HbA1c ≤ 8.5%), and was higher than prebreakfast PG (221 ± 62 vs. 199 ± 49 mg/dl, P ≤ 0.01) in those demonstrating poor diabetic control (HbA1c ≤ 8.5%). Prebreakfast, prelunch, postlunch, and extended postlunch PG values were all significantly correlated with HbA1c. Multiple linear regression analysis demonstrated that postlunch PG and extended postlunch PG correlated significantly and independently with HbA1c, but that prebreakfast PG and prelunch PG did not. Moreover, postlunch PG and extended postlunch PG demonstrated better sensitivity, specificity, and positive predictive value in predicting poor glycemic control than did prebreakfast PG or prelunch PG. CONCLUSIONS In type 2 diabetes, postlunch PG and extended postlunch PG are better predictors of glycemic control than fasting plasma glucose (FPG). We therefore suggest that they be more widely used to supplement, or substitute for, FPG in evaluating the metabolic control of type 2 diabetic patients.

Assessment of insulin sensitivity from plasma insulin and glucose in the fasting or post oral glucose-load state.

OBJECTIVE: To compare insulin sensitivity indexes derived from plasma insulin (I) and glucose (G) in the basal state (Sib) and at the second hour (I2h and G2h) of an oral glucose tolerance test (OGTT, Si2h) (i) with measurements of insulin sensitivity using the insulin modified frequently sampled intravenous glucose tolerance test (FSIVGTT) [Si(IVGTT)] and (ii) with modelling of fasting glucose and insulin by the homeostasis model assessment (HOMA).SUBJECTS: 47 subjects entered the study. 31 subjects were classified as having normal glucose tolerance (NGT), 10 as having impaired tolerance to glucose (IGT) and six as type 2 diabetes mellitus according to the World Health Organisation (WHO) criteria.MEASUREMENTS: Sib and Si2h were calculated as follows. Sib=108/(I×G×VD), Si2h=108/(I2hr×G2hr×VD) where VD is an estimate of the apparent glucose distribution volume. A third insulin sensitivity index (SiM) was calculated by averaging Sib and Si2h. HOMA was calculated as follows: I/(22.5×e−lnG)RESULTS: Si(IVGTT), Sib, SI2h and SiM were all significantly higher in subjects with NGT than in those with IGT or type 2 diabetes. Si(IVGTT) was highly correlated (P≤0.0001) with the three insulin sensitivity indexes found in the total population, in subjects with NGT and in those with IGT. In type 2 diabetic patients, a significant correlation was only noted when SiM was tested against Si(IVGTT) (P≤0.05). In most circumstances, the associations of Si(IVGTT) with Sib, SI2h and SiM were stronger than the corresponding associations with Ib, I2h or HOMA. SiM was the index that correlated best with Si(IVGTT) in the whole group (r=0.92, P<0.0001) as well as in NGT (r=0.86, P<0.0001), IGT (r=0.96; P<0.0001) and type 2 diabetes (r=0.83, P≤0.05) subgroups.CONCLUSIONS: Calculations of sensitivity indexes from G and I concentrations in the basal state and during a conventional 2 h OGTT appear to be useful for coupling in the same simple and single test both a determination of glucose tolerance and an estimate of insulin sensitivity.

Long-Term Outcome and Disability of Diabetic Patients Hospitalized for Diabetic Foot Ulcers: A 6.5-year follow-up study

OBJECTIVE—The long-term outcome and functional status of subjects hospitalized for diabetic foot ulcers have been poorly studied and thus are the topics of this study. RESEARCH DESIGN AND METHODS—Ninety-four consecutive diabetic subjects hospitalized for diabetic foot ulcers between January 1998 and December 2000 were prospectively followed for mean ± SD 79.5 ± 13.3 months. We calculated rates of primary healing, new ulcers, amputations, mortality, and disability and evaluated the global therapeutic success (GTS) of foot care management as defined by the association of primary healing without recurrence or disability at the end of follow-up. RESULTS—Follow-up was successful in 89 of 94 subjects (63 men and 31 women; age 63.7 ± 10.8 years). Of these, 69 (77.5%) experienced primary healing without major amputation, 39 (43.8%) underwent amputation (24 minor and 15 major), and 46 died (51.7%), including 23 from cardiovascular events. Forty-two of 69 patients who experienced primary healing (60.9%) had ulcer recurrence. At the end of the follow-up period, 25 patients (28.1%) were dependent and 40 subjects (44.9%) had achieved GTS. Multivariate analysis showed the role of age as an independent predictor of GTS (P < 0.05) and of impaired renal function/albuminuria as independent predictors of healing failure, first amputation, and mortality (P < 0.01). CONCLUSIONS—Despite a satisfactory initial healing rate, the global long-term outcome of patients hospitalized for diabetic foot ulcers was poor. Nephropathy appears to be an important predictor of long-term outcome. Further studies are needed to establish recognized criteria for therapeutic success going beyond just the evaluation of healing rate in the management of diabetic foot ulcers.

Grape Polyphenols Prevent Fructose- Induced Oxidative Stress and Insulin Resistance in First-Degree Relatives of Type 2 Diabetic Patients

OBJECTIVE To assess the clinical efficacy of nutritional amounts of grape polyphenols (PPs) in counteracting the metabolic alterations of high-fructose diet, including oxidative stress and insulin resistance (IR), in healthy volunteers with high metabolic risk. RESEARCH DESIGN AND METHODS Thirty-eight healthy overweight/obese first-degree relatives of type 2 diabetic patients (18 men and 20 women) were randomized in a double-blind controlled trial between a grape PP (2 g/day) and a placebo (PCB) group. Subjects were investigated at baseline and after 8 and 9 weeks of supplementation, the last 6 days of which they all received 3 g/kg fat-free mass/day of fructose. The primary end point was the protective effect of grape PPs on fructose-induced IR. RESULTS In the PCB group, fructose induced 1) a 20% decrease in hepatic insulin sensitivity index (P < 0.05) and an 11% decrease in glucose infusion rate (P < 0.05) as evaluated during a two-step hyperinsulinemic-euglycemic clamp, 2) an increase in systemic (urinary F2-isoprostanes) and muscle (thiobarbituric acid–reactive substances and protein carbonylation) oxidative stress (P < 0.05), and 3) a downregulation of mitochondrial genes and decreased mitochondrial respiration (P < 0.05). All the deleterious effects of fructose were fully blunted by grape PP supplementation. Antioxidative defenses, inflammatory markers, and main adipokines were affected neither by fructose nor by grape PPs. CONCLUSIONS A natural mixture of grape PPs at nutritional doses efficiently prevents fructose-induced oxidative stress and IR. The current interest in grape PP ingredients and products by the global food and nutrition industries could well make them a stepping-stone of preventive nutrition.

Antioxidants and glucose metabolism disorders.

Purpose of reviewRecent evidence suggests that oxidative stress is a cornerstone of the metabolic mechanisms by which overfeeding leads to insulin resistance. This review is an update of the most recent arguments in favor of this theory and of the possible role of antioxidants. Recent findingsReactive oxidative species (ROS) are produced by multiple pathways within the cell and are essential for many cellular functions. ROS production is balanced by enzymatic and nonenzymatic antioxidant systems. The perturbation of the pro-oxidant/antioxidant balance can lead to increased oxidative damage of macromolecules, a phenomenon known as ‘oxidative stress’. ROS are involved both in insulin signal transduction and in insulin resistance when produced in excess. Overfeeding, saturated fatty acids, and obesity play a key role in the excessive production of ROS. However, a diet rich in fruits and vegetables, and therefore antioxidants, has demonstrated beneficial effects against oxidative damages and insulin resistance. SummaryExperimental data are in favor of a beneficial role of antioxidants in glucose metabolism, but clinical data in humans are more controversial. Even if a diet rich in fruits and vegetables could provide an optimal mix of antioxidants, it remains unclear whether supplementation with antioxidants alone can reproduce the same effect.

Dietary antioxidants: Do they have a role to play in the ongoing fight against abnormal glucose metabolism?

Overfeeding, an increased intake of saturated fatty acids, and sugary foods are key dietary changes that have occurred in recent decades in addition to the emergence of the obesity epidemic. In addition to an increase in energy storage as fat, these dietary changes are accompanied by an increase in mitochondrial macronutrient oxidation, leading to an excessive free radical production and, hence, oxidative stress. The latter has long been considered a central mechanism linking nutrient overload, insulin resistance, the metabolic syndrome, and diabetes. However, food, through fruit and vegetable consumption, also can be a great source of antioxidants that protect the body against oxidative damage and insulin resistance and thus help cope with the metabolic backlash of the energy-dense Westernized diet. Experimental data are in favor of the beneficial role conveyed by antioxidants in glucose metabolism, but clinical data in humans remain controversial. This review therefore aimed to sort out any underlying discrepancies and provide an overall clear view of the role of antioxidants in the ongoing fight against abnormal glucose metabolism.

Effects of Lifestyle Interventions That Include a Physical Activity Component in Class II and III Obese Individuals: A Systematic Review and Meta-Analysis

Background In class II and III obese individuals, lifestyle intervention is the first step to achieve weight loss and treat obesity-related comorbidities before considering bariatric surgery. A systematic review, meta-analysis, and meta-regression were performed to assess the impact of lifestyle interventions incorporating a physical activity (PA) component on health outcomes of class II and III obese individuals. Methods An electronic search was conducted in 4 databases (Medline, Scopus, CINAHL and Sportdiscus). Two independent investigators selected original studies assessing the impact of lifestyle interventions with PA components on anthropometric parameters, cardiometabolic risk factors (fat mass, blood pressure, lipid and glucose metabolism), behaviour modification (PA and nutritional changes), and quality of life in adults with body mass index (BMI) ≥ 35 kg/m2. Estimates were pooled using a random-effect model (DerSimonian and Laird method). Heterogeneity between studies was assessed by the Cochran’s chi-square test and quantified through an estimation of the I ². Results Of the 3,170 identified articles, 56 met our eligibility criteria, with a large majority of uncontrolled studies (80%). The meta-analysis based on uncontrolled studies showed significant heterogeneity among all included studies. The pooled mean difference in weight loss was 8.9 kg (95% CI, 10.2–7.7; p < 0.01) and 2.8 kg/m² in BMI loss (95% CI, 3.4–2.2; p < 0.01). Long-term interventions produced superior weight loss (11.3 kg) compared to short-term (7.2 kg) and intermediate-term (8.0 kg) interventions. A significant global effect of lifestyle intervention on fat mass, waist circumference, blood pressure, total cholesterol, LDL-C, triglycerides and fasting insulin was found (p<0.01), without significant effect on HDL-C and fasting blood glucose. Conclusions Lifestyle interventions incorporating a PA component can improve weight and various cardiometabolic risk factors in class II and III obese individuals. However, further high quality trials are needed to confirm this evidence, especially beyond weight loss.

Use of a prostacyclin analogue in cholesterol crystal embolism

The prognosis of cholesterol embolism is often poor, and no treatment is presently available. We report the use of a stable prostacyclin analogue in treating cholesterol embolism in a diabetic patient with arteriopathy. As a sole therapy, it improved cutaneous manifestations and pain, in parallel with an increased transcutaneous oxymetry. We think that prostacyclin analogues are novel candidates for the treatment of cholesterol embolism.

Health-related quality of life and stages of behavioural change for exercise in overweight/obese individuals.

BACKGROUND Stages of change in exercise behaviour have been shown to be associated with health-related quality of life (HRQoL) in overweight/obese adults. However, studies examining this relationship have not used questionnaires specifically designed for such a population. The present study assessed the impact of stages of change (SOC) for exercise, using the transtheoretical model, on the HRQoL, using the quality of life, obesity and dietetics (QOLOD) scale, an obesity-specific QoL questionnaire. Our hypothesis was that the more people are in the advanced stages of behavioural change, the better their HRQoL. METHODS A total of 214 consecutive obese individuals (148 women/66 men, mean age 47.4 ± 14.0 years, BMI 37.2 ± 8.4 kg/m2) were included in the cross-sectional study, and all completed SOC and QOLOD questionnaires. RESULTS Multivariate analysis of covariance (MANCOVA) established significant effects on the overall composite of the five dimensions of the QOLOD (P < 0.001). Analysis of covariance (ANCOVA) further determined the significant effect of SOC in terms of physical impact (P < 0.001) and psychosocial impact (P < 0.01), with marginally significant effects on sex life (P = 0.07), but no impact on comfort with food (P = 0.13) or on the dieting experience (P = 0.13), two dimensions evaluating attitudes toward food. CONCLUSION In obese/overweight individuals, the HRQoL varies with the SOC, with those in the more advanced behavioural stages reporting better HRQoL. However, dimensions related to food showed no differences according to SOC, confirming the complexity of the relationship between exercise and nutrition, and the need for further studies to acquire a more complete understanding of their underlying mechanisms.

Myocardial perfusion imaging and cardiac events in a cohort of asymptomatic patients with diabetes living in southern France

Aims  To assess the association between abnormal stress myocardial perfusion imaging (MPI) and cardiac events (CE) in asymptomatic patients with diabetes and with ≥ 1 additional risk factor. Predictors of abnormal stress MPI were also evaluated.