Salvatore Caputo

Meta-Analysis of Impact of Different Types and Doses of Statins on New-Onset Diabetes Mellitus

Recent reports indicate that statins are associated with an increased risk for new-onset diabetes mellitus (DM) compared with placebo and that this relation is dose dependent. The aim of this study was to perform a comprehensive network meta-analysis of randomized controlled trials (RCTs) investigating the impact of different types and doses of statins on new-onset DM. RCTs comparing different types and doses of statins with placebo were searched for using the MEDLINE, Embase, and Cochrane databases. A search of RCTs pertinent to this meta-analysis covering the period from November 1994 to October 2012 was conducted by 2 independent investigators using the MEDLINE, Cochrane, Google Scholar, and Embase databases as well as abstracts and presentations from major cardiovascular meetings. Seventeen RCTs reporting the incidence of new-onset DM during statin treatment and including a total of 113,394 patients were identified. The RCTs compared either a statin versus placebo or high-dose versus moderate-dose statin therapy. Among different statins, pravastatin 40 mg/day was associated with the lowest risk for new-onset DM compared with placebo (odds ratio 1.07, 95% credible interval 0.86 to 1.30). Conversely, rosuvastatin 20 mg/day was numerically associated with 25% increased risk for DM compared with placebo (odds ratio 1.25, 95% credible interval 0.82 to 1.90). The impact on DM appeared to be intermediate with atorvastatin 80 mg/day compared with placebo (odds ratio 1.15, 95% credible interval 0.90 to 1.50). These findings were replicated at moderate doses. In conclusion, different types and doses of statins show different potential to increase the incidence of DM.

Schizophrenic symptoms and SPECT abnormalities in a coeliac patient : regression after a gluten-free diet

De Santis A, Addolorato G, Romito A, Caputo S, Giordano A, Gambassi G, Taranto C, Manna R, Gasbarrini G (Catholic University, Rome, Italy). Schizophrenic symptoms and SPECT abnormalities in a coeliac patient: regression after a gluten‐free diet (Case Report). J Intern Med 1997; 242: 421–23.

Nonselective Loss of Contrast Sensitivity in Visual System Testing in Early Type I Diabetes

Objective Psychophysical methods in patients with diabetes mellitus reveal deficits of central or foveal vision. Our aim was to evaluate the contrast-sensitivity thresholds in 24 insulin-dependent (type I) diabetic patients with a short disease duration and without retinopathy, taking into account metabolic control. Research Design and Methods The control group consisted of age-matched nondiabetic subjects. None had visual or systemic symptoms. Contrast sensitivity measured at eight different spatial frequencies to sinusoidal bar patterns of 0.6–12.2 cycles/deg can detect functional defects in the spatially sensitive retinal ganglion cells or in higher visual pathways. We performed two different temporal types of contrast-sensitivity testing, dynamic (8 Hz) and static (0 Hz). Results Significant losses with dynamic contrast-sensitivity test at all but the highest spatial frequencies (i.e., 12.2 cycles/deg) were shown, whereas there was significant attenuation of contrast sensitivity at five spatial frequencies (1.0, 1.4, 2.2, 7.1, and 9.6 cycles/deg) in the static mode. Grating losses (<2SD of control means) of contrast sensitivity were found in 33.3% (dynamic) and in 72.9% (static) of eyes of diabetic patients. HbA1c values were positively correlated at variable spatial frequencies (1.0, 1.4, and 2.2 cycles/deg for dynamic test and 0.6, 1.0, 1.4, 2.2, 4.8, and 7.1 cycles/deg for static test). Conclusions Our results suggest an early, generally nonselective neuronal damage of visual pathways that occurs before the onset of clinically detectable retinopathy. The visual deficit may be related directly to the effects of diabetes; repetitive minor hypoglycemic insults may contribute more than a marked hyperglycemic condition to the mechanisms underlying physiological changes along the optic nerve.

Chronic taurine supplementation ameliorates oxidative stress and Na+K+ATPase impairment in the retina of diabetic rats

Summary. This study evaluates the effect of 4 months supplementation with 2% and 5% taurine (w/w) on the retina of diabetic rats. In non-diabetic rats, taurine does not modify glycemia, body weight, retinal conjugated dienes (CD), lipid hydroperoxide (LP), and Na+K+ATPase activity. In diabetic rat, at 2, 4, 8, 16 weeks following the onset of diabetes, retinal CD and LP are significantly and progressively increased, while pump activity is gradually and significantly reduced. In taurine supplemented diabetic rats, glycemia is not affected but lipid peroxidation is significantly decreased. Finally, taurine preserves ATPase activity being 5% more effective than 2% taurine. We conclude that taurine supplementation ameliorates biochemical retinal abnormalities caused by diabetes, thereby suggesting that taurine may have a role in the prevention of retinal changes in diabetes.

Detection of inner retina dysfunction by steady-state focal electroretinogram pattern and flicker in early IDDM

The effects of diabetes on the neural retina before the onset of clinically detectable retinopathy can be investigated with electrophysiological methods. Our aim was to detect early retinal dysfunctions in 60 patients with insulin-dependent diabetes mellitus (IDDM) and with a short duration of disease. We used the steady-state focal (9° field size) electroretinogram (ERG) of the macula in response to luminance modulation of a uniform field (flicker ERG) or to counterphase-modulated sinusoidal gratings (pattern ERG). The harmonic analysis of flicker ERG and pattern ERG yielded three main components: a first and a second harmonic to flicker (1F and 2F, respectively) and a second harmonic to pattern (2P). The 1F is believed to be correlated to photoreceptor activity, whereas 2F and 2P represent different subsets of generators in the inner retina. Results of focal ERG in IDDM patients with no or early retinopathy were compared with age-matched control subjects. Mean 2F and 2P amplitudes were significantly reduced in IDDM patients compared with the control group (P = 0.0001 by analysis of variance). 2P but not 2F amplitude was significantly more reduced in patients with retinopathy than in those without retinopathy (P < 0.05). 2F but not 2P phase abnormalities were observed in some patients. 2F and 2P alterations were slightly correlated with metabolic control (r = 0.22, P = 0.02) and disease duration (r = 0.28, P = 0.003). 1F was not significantly altered in IDDM patients. Our results suggest that early diabetes causes selective neurosensory deficits of inner retina layers, whereas the photoreceptors appear unaffected.

Effect of carbohydrate counting and medical nutritional therapy on glycaemic control in Type 1 diabetic subjects: a pilot study.

Diabet. Med. 27, 477–479 (2010)

Evidence for Early Impairment of Macular Function With Pattern ERG in Type I Diabetic Patients

The electroretinogram (ERG) elicited by alternating gratings at constant mean luminance (pattern ERG) is a focal response reflecting the activity of the directly stimulated retinal area. In addition, pattern ERG is related, unlike the flash ERG, to ganglion cell activity. Therefore, this technique may be used to evaluate the integrity of inner retinal layers in the macular region. In this study, the steady-state pattern ERG, in response to alternating gratings (1.7 cycles/deg spatial frequency; 9° field size) temporally modulated at 8 Hz, was recorded in 42 type I (insulin-dependent) diabetic patients with zero to four microaneurysms on fluorescein angiography and a duration of disease <11 yr. No patient had concomitant ocular or systemic complications. Mean pattern-ERG amplitude was significantly reduced in patients compared with age-matched control subjects (analysis of variance, F = 25.6, P < 0.0001). Significant differences were observed between control and diabetic subjects without retinopathy (Scheffe Ftest, P < 0.0001), between control and retinopathic subjects (Scheffe F test, P < 0.0001), and between diabetic patients without retinopathy and those with early retinopathy (Scheffé F test, P < 0.02). Pattern-ERG amplitude was inversely correlated with duration of diabetes (r = 0.22, P < 0.05). Our results suggest a macular dysfunction in early diabetes resulting from metabolic and/or vascular injuries in the neurosensory retina.

Screening, evaluation and management of depression in people with diabetes in primary care.

Family physicians are responsible for diagnosing and treating the majority of people with type 2 diabetes mellitus and co-morbid depression. As a result of the impact of co-morbid depression on patient self-care and treatment outcomes, screening for depression in the context of a structured approach to case management and patient follow up is recommended in people with diabetes and cardiovascular disease. This review summarizes the need for improved recognition and treatment of depression in diabetes; and makes expert recommendations with regard to integrating screening tools and therapies into a busy family or general medical practice setting.

Steady-state pattern electroretinogram in insulin-dependent diabetics with no or minimal retinopathy

Steady-state pattern electroretinogram (PERG) in response to sinusoidal gratings (1.7 c/deg spatial frequency; 9 × 9 deg field size) temporally modulated (sinusoidally) at 8 Hz were recorded in 40 insulin-dependent diabetics and 28 age-matched normal subjects. Visual acuity was ⩾ 20/20 in all 40 patients; 31 (62 eyes) showed no sign of retinopathy and nine (18 eyes) showed a few microaneurysms on fluorescein angiography. Insulin-dependent diabetics showed a significant reduction in the PERG mean amplitude as compared with age-matched control subjects (one-way analysis of variance: p < 0.0001). Significant differences were observed between normals and diabetics without retinopathy (Scheffé test: p < 0.0001), normals and diabetics with early retinopathy (Scheffé test: p < 0.0001), no retinopathy and early retinopathy patients (Scheffé test: p < 0.05). In diabetics without retinopathy multi-factorial analysis of variance revealed a significant effect of age of onset of the disease (p < 0.01) and an interaction effect between age of onset and duration (p < 0.001) on PERG amplitude. These results suggest a possible use of the steady-state PERG to detect early macular dysfunction in insulin-dependent diabetics.

Association Between Osteoprotegerin G1181C and T245G Polymorphisms and Diabetic Charcot Neuroarthropathy: A case-control study

OBJECTIVE Charcot neuroarthropathy is a disabling complication of diabetes. Although its pathogenesis remains unknown, we suppose that genetics may play a relevant role. RESEARCH DESIGN AND METHODS We performed a case-control study with 59 subjects with diabetic Charcot neuroarthropathy (Ch group), 41 with diabetic neuropathy without Charcot neuroarthropathy (ND group), and 103 healthy control subjects (H group) to evaluate the impact of two single nucleotide polymorphisms (SNPs) of the osteoprotegerin gene (G1181C and T245G) on the risk of Charcot neuroarthropathy. RESULTS Regarding the SNPs of G1181C, we found a significant linkage between the G allele and Charcot neuroarthropathy (Ch vs. ND, odds ratio [OR] 2.32 [95% CI 1.3–4.1], P = 0.006; Ch vs. H, 2.10 [1.3–3.3], P = 0.002; and ND vs. H, 0.90 [0.7–1.9], P = 0.452); similarly, we found a linkage with the G allele of T245G (Ch vs. ND, 6.25 [2.2–19.7], P < 0.001; Ch vs. H, 3.56 [1.9–6.7], P = 0.001; and ND vs. H, 0.54 [0.6–5.7], P = 0.304), supporting a protective role for the allele C and T, respectively. For this reason we investigated the frequency of the protective double homozygosis CC + TT (7% in Ch) that was significantly lower in Ch compared with H (0.18 [0.06–0.5], P = 0.002) and with ND (0.17 [0.05–0.58], P = 0.006), whereas there was no difference between H and ND (1.05 [0.43–2.0], P = 0.468). In a multivariate logistic backward regression model, only weight and the lack of CC and TT genotypes were independently associated with the presence of Charcot neuroarthropathy. CONCLUSIONS This is the first study that shows an association between genetic regulation of bone remodeling and Charcot neuroarthropathy.