Emilia Ragno

Effects of simvastatin and atorvastatin administration on insulin resistance and respiratory quotient in aged dyslipidemic non-insulin dependent diabetic patients

One hundred and ninety-five aged (mean age: 67+/-4.8 years), non-insulin dependent diabetic patients underwent a randomised single-blind study for investigating the effect of statin administration on insulin resistance and respiratory quotient. After 4 weeks run-in period, all patients were randomised in three groups: placebo (n=67), simvastatin (10 mg/day) (n=61) and atorvastatin (5 mg/day) (n=67). Each treatment period lasted 8 weeks. At the beginning, after the run-in and at the end of the study, insulin resistance was assessed by homeostasis model assessment (HOMA) index, while respiratory quotient (Rq) was evaluated by indirect calorimetry. Statins versus placebo significantly lowered plasma total, LDL-, HDL-cholesterol and triglyceride concentrations and improved insulin resistance and Rq and metabolic control. Atorvastatin had a greater effect than simvastatin on plasma triglyceride concentration (-26.3+/-3.1 vs. -19.7+/-2.8%, P<0.03), HOMA index (-13.1+/-0.6 vs. -9.1+/-0.9%, P<0.05), Rq (5.9+/-0.4 vs. 3.1+/-0.5%, P<0.05) and glycosylated haemoglobin (-11.2+/-0.3 vs. -7. 1+/-0.4%, P<0.05). In the whole group of subjects (n=195) and at the end of the study, changes in plasma triglyceride concentrations were significantly correlated with the change in the HOMA index (r=0.44, P<0.001) and age and BMI adjusted-Rq (r=-0.32, P<0.005). Multivariate analyses demonstrated that decline in plasma triglyceride concentration was a significant determinant for explaining the effect of statin on insulin resistance and Rq. In conclusion our study demonstrates that statin administration is useful for controlling dyslipidemia in NIDDM patients and for improving the metabolic control. With regard to this latter aim, atorvastatin seems to be more powerful than simvastatin.

New aspects of the insulin resistance syndrome: impact on haematological parameters

Abstract.Aim/hypothesis: Previous studies have shown that insulin has an important in vitro role in the regulation of human erythropoiesis. We investigated whether in vivo hyperinsulinaemia/insulin resistance affects haematological parameters. Methods: A total of 608 subjects between 22 and 99 years of age were enrolled in the Chianti study, an epidemiological study of factors affecting mobility in old age. The degree of insulin resistance was assessed using the homeostasis model. Results: We found a correlation between insulin resistance and red blood cell count, (r = 0.14 p < 0.001), plasma haemoglobin (r = 0.16 p < 0.001), haematocrit (r = 0.15 p < 0.001) and plasma iron (r = 0.1 p < 0.05) concentrations. Red blood cell count was also associated with the other biological markers of insulin resistance syndrome. Subjects with higher insulin resistance (4 ° quartile) had higher red blood cell count, plasma triglycerides and low density lipoproteins (LDL) cholesterol concentrations and lower high density lipoproteins (HDL) cholesterol concentrations then subjects at the lowest quartiles of insulin resistance. Insulin resistance and BMI were significant and independent predictors of red blood cell count even when the analysis was adjusted for age, sex, waist-to-hip ratio, plasma iron and drug intake. Conclusion/hypothesis: Our findings provide in vivo evidence of a relation between hyperinsulinaemia/insulin resistance, the main variables of insulin resistance syndrome and erythropoiesis. Increased red blood cell count could be considered as a new aspect of the insulin resistance syndrome that could contribute to the increased risk of developing cardiovascular problems. [Diabetologia (2001) 44: 1232–1237]

Gender specific association of genetic variation in peroxisome proliferator-activated receptor (PPAR)γ-2 with longevity

Long-lived subjects have been shown to have peculiar anthropometric features (i.e. lower body mass index (BMI)) and metabolic parameters (i.e. improved insulin sensitivity). Life style and a genetic background potentially protective against the age-related metabolic derangement might contribute to such a particular phenotype. Peroxisome proliferator-activated receptor (PPAR)gamma-2 is an important regulator of adipose tissue metabolism, insulin sensitivity and inflammatory response. Thus, the potential role of genetic variability at Pro/Ala loci of PPARG gene on longevity was studied in 222 long-lived subjects and 250 aged subjects. We found a different Pro/Ala genotype frequency distribution between long-lived and aged men subjects, long-lived men having an increased frequency of Pro/Ala genotype (20 vs 8.5%); no differences was found when allele and genotype distribution of Pro/Ala gene polymorphism were analyzed in the two age group of women. Interestingly, subjects with Pro/Ala polymorphism had significantly lower BMI than Ala/Ala and Pro/Pro polymorphism. In conclusion, our study demonstrated that paraoxonase Pro/Ala gene polyporphism is associated with human longevity. Such an effect is probably due to the effect of Pro/Ala polymorphism on body composition and appears to be gender specific.

Is dermolipectomy effective in improving insulin action and lowering inflammatory markers in obese women

Objective  Obesity is a major risk factor for coronary heart disease, and surgical treatment of obese patients as part of a multidisciplinary approach seems to provide faster results than diet therapy. The aim of this study was to evaluate the effect of dermolipectomy on insulin action and inflammatory markers in 20 obese women.

Evidence for reduction of pro-atherosclerotic properties in platelets from healthy centenarians.

The aim of the present study was to investigate if aging is associated with platelet membrane modifications possibly related with cellular activation and hyperaggregability and if platelets from centenarians show different properties which might play a role in successful aging and longevity. Platelet plasma membranes were obtained from 60 healthy subjects, divided into four groups according to the age range: (1) 21-39 years; (2) 40-59 years; (3) 60-79 years; (4) centenarians (>/=100 years). Both centenarians and control subjects were submitted to the following inclusion criteria: liver, kidney, and thyroid function tests within the normal range; absence of history of diabetes, hypertension or coronary heart disease; no signs of edema or dehydration; no drug or vitamin supplement in the 4 weeks before the study; absence of Alzheimers disease or secondary dementia. The following determinations were performed: lipid peroxide levels (Lp) evaluated by the measurement of thiobarbituric acid (TBA) reactivity, fluidity studied by the fluorescence anisotropy of the probe 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), Na(+)/K(+)-ATPase activity measured by the method of Kitao and Hattori, and sialic acid (SA) content evaluated by the periodate-thiobarbituric acid method. Centenarians showed: (i) Lp concentrations lower than elderly subjects; (ii) increased Na(+)/K(+)-ATPase activity compared with adult and elderly subjects; (iii) higher TMA-DPH anisotropy than elderly subjects; (iv) SA content similar to the young and adult groups.The present work found deep platelet membrane modifications in centenarians compared with elderly subjects. These changes are likely associated with a decreased platelet activation and therefore might exert a protective role against cardiovascular accidents, as platelet activation is a key event in the initiation and progression of arteriosclerosis.

Residual C-peptide secretion and endothelial function in patients with Type II diabetes.

Recent studies have demonstrated that C-peptide exerts beneficial effects on endothelial function. To investigate the relationship between residual pancreatic C-peptide secretion and endothelial function in patients with well controlled or poorly controlled Type II diabetes, we studied 100 patients with Type II diabetes that were free from diabetic neuropathy. In all patients, insulin resistance, residual pancreatic C-peptide secretion, endothelial function and oxidative stress were investigated using the homoeostasis model assessment (HOMA) index, glucagon bolus test, brachial reactivity, Trolox equivalent antioxidant capacity (TEAC) and thiobarbituric acid-reacting substances (TBARS). The patients were categorized into quartiles on the basis of plasma HbA(1c) (glycated haemoglobin) concentration. Analysis of the data showed significant increases in plasma glucose concentration, HOMA index, microalbuminuria and TBARS, and significant decreases in plasma C-peptide, AUC (area under the curve) plasma C-peptide and TEAC, through the different quartiles (from the lowest to the highest HbA(1c) concentration). With regard to parameters of endothelial function, changes in diameter showed a significant declining trend through the different quartiles. Endothelial-dependent changes in diameter were independently and significantly associated with AUC C-peptide levels, TEAC and TBARS. In conclusion, our study demonstrated that patients with Type II diabetes with good residual C-peptide secretion are better protected from endothelial dysfunction that those with poor C-peptide secretion.

Relationship between autonomic cardiac activity, b-cell function, anthropometrics and metabolic indices in type II diabetics

objective Recent studies have demonstrated that C‐peptide exerts beneficial effects on the diabetic state, including improvements in kidney and nerve function. Thus, we investigated the effect of residual pancreatic C‐peptide secretion on the cardiac autonomic nervous system in well‐ and poorly controlled type II diabetic patients.