Giuseppe Lepore

Lipids and Renal Disease

Chronic renal disease is accompanied by characteristic abnormalities of lipid metabolism, which appear as a consequence of nephrotic syndrome or renal insufficiency and are reflected in an altered apolipoprotein profile as well as elevated plasma lipid levels. Experimental and clinical studies have suggested a correlation between the progression of renal disease and dyslipidemia. High cholesterol and triglyceride plasma levels have been demonstrated to be independent risk factors for progression of renal disease in humans. The underlying pathophysiologic mechanisms for the relationship between lipid levels and progression of renal disease are not yet fully understood, although there are data that oxidative stress and insulin resistance may mediate the lipid-induced renal damage. In the animal model, lipid-lowering agents seem to ameliorate glomerular damage, preventing glomerulosclerosis and interstitial fibrosis. Although evidence from clinical studies indicates that statin therapy is associated with significant benefit in individuals with established chronic renal failure, whether lipid reduction can slow the renal functional decline awaits a primary renal outcome lipid-lowering therapy study.

Bolus calculator improves long-term metabolic control and reduces glucose variability in pump-treated patients with Type 1 diabetes

Recently insulin pumps were added with bolus calculator to determine the insulin dose, taking into account current and target blood glucose, carbohydrate intake, carbohydrateto-insulin ratio, insulin sensitivity factor (ISF) and duration of insulin action. Few studies evaluated the clinical usefulness of this tool [1e3]. We evaluated one-year efficacy of bolus calculator on long-term glycemic control and glucose variability in 30 Type 1 diabetic patients (17 males, 13 females, age 44 12 years, duration of diabetes 25 10 years) already treated with continuous subcutaneous insulin infusion (CSII) (duration of CSII 64 14 months) that started using a bolus calculator. All patients, already trained to “carbohydrate counting” and ISF to determine insulin dosing, received a 2-h individual education session before switching from a pump without bolus calculator to a new pump with automated bolus calculator. Physicians set up bolus parameters. ISF was calculated using the ratio 1700/daily insulin dose and subsequently modified (when necessary) based on individual blood glucose measurements. HbA1c, BMI, insulin requirement and severe hypoglycemia were evaluated every three months the year before and after the use of bolus calculator. Three seven-point capillary blood glucose profiles and glucose variability (determined by interstitial glucose concentration measured continuously over 72 h) were assessed one month before and after one-year of bolus calculator usage. Both meal composition and the amount of carbohydrates at breakfast, lunch and dinner were similar on those days. Also duration and intensity of exercise were reproducible. Glucose variability was calculated by continuous overall net glycemic action (CONGA2 and CONGA4), evaluated in the temporal division between day (0700e2300 h) and night (2300e0700 h) [4] and mean of daily differences (MODD) [5]. Data are expressed as mean SD. Differences between means were tested using the paired t test or analysis of variance.

Poor Glucose Control in the Year Before Admission as a Powerful Predictor of Amputation in Hospitalized Patients With Diabetic Foot Ulceration

Although there is a strong association between lower-extremity amputation (LEA) and HbA1c (A1C) in diabetic patients (1,2), little information is available on glucose control in the period preceding and following LEA (3). Our objective was to evaluate the predictors of LEA and to examine the role of blood glucose control during the year before and the year after admission. A total of 122 diabetic patients (82 men and 40 women aged 69.7 ± 10.9 years, disease duration 19.7 ± 10.4 years) consecutively admitted for diabetic foot ulcers to the Medicine Department of United Hospitals of Bergamo between January 2003 and December 2004 were enrolled in our observational study and assigned to one …

The effect of various blood glucose levels on post-glucagon C-peptide secretion in type 2 (non insulin-dependent) diabetes

We investigated how different plasma glucose concentrations could significantly modify the C-peptide response to glucagon. Twenty poorly-controlled (HbA1c 10.2 ± 1.5%) non insulin-dependent (NIDDM) subjects (body mass index 27 ± 1.8), 2 treated with diet alone and 18 with oral hypoglycemic agents were studied. The first day glucagon (1 mg iv) was injected, patients being fasting and untreated. Mean plasma glucose levels were 11.4 ± 1.2 mM. On a second non consecutive day, after an overnight fast, the same patients were connected to a closed-loop insulin infusion system (Betalike, Genoa), their blood glucose concentrations were stabilized within a normoglycemic range (5–5.5 mM) for 2 h and insulin infusion was stopped. The glucagon test was repeated 30 min later. Blood samples were taken 0, 6, 10, 20 min after glucagon injection. In the second test, basal, and 6,10 and 20 min post-glucagon glucose levels were significantly lower (p < 0.001); similarly C-peptide concentrations were significantly reduced both in basal conditions (0.55 ± 0.04 vs 0.37 ± 0.04 nM; p < 0.001) and 6 (0.92 ± 0.06 vs 0.6 ± 0.06; p < 0.001), 10 (0.79 ± 0.06 vs 0.56 ± 0.06; p < 0.001) and 20 min (0.64 ± 0.05 vs 0.44 ± 0.04; p < 0.001) after stimulation. The C-peptide secretion area showed the same trend (49.5 +4.8 vs 32.1 ±5.8; p< 0.001). In conclusion, our data confirms that blood glucose levels modulate the pancreatic insulin secretion; glycémie normalization significantly reduced both basal and post-glucagon C-peptide release.

Continuous Subcutaneous Insulin Infusion Is Better Than Multiple Daily Insulin Injections in Reducing Glucose Variability Only in Type 1 Diabetes With Good Metabolic Control

A possible advantage of continuous subcutaneous insulin infusion (CSII) therapy in type 1 diabetes is the decrease of glucose excursions with respect to multiple daily injections (MDI) of insulin. Few studies investigated this aspect of insulin treatment using continuous glucose monitoring systems (1). The aim of our study was to evaluate whether CSII reduces glucose variability with respect to MDI, in patients with comparable A1C levels. The analysis was conducted in 36 type 1 diabetic patients, treated with CSII (15 male and 21 female subjects, aged 35 ± 12 years, duration of diabetes 16 ± 11 years, A1C 8.3 ± 1.5%) and 77 patients treated with MDI (35 male and 42 female subject, aged 40 ± 15 years, duration of …

Effects of a somatostatin derivative (SMS 201–995) on postprandial hyperglycemia in insulin-dependent diabetics studied by means of a closed-loop device

We studied the effects of a premeal sc injection of an analog of somatostatin (SMS 201–995, Sandoz) on the postprandial glycemic excursions, insulin requirement and hormone profiles (GH, glucagon and C-peptide) in 8 IDDM patients (diabetes duration 14.0 ± 6.5 yr, daily insulin requirement 36 ± 6.4 U) maintained normoglycemic by connecting them to a closed-loop insulin infusion system (Betalike, Genoa). The morning of the test the patients were connected to the Betalike and their glucose levels stabilized for at least 4 h. At 13:00 h the study was begun with a sc injection of 50 μg of SMS 201–995 or placebo (randomly) and a standardized mixed meal (800 Kcal) was given. Blood samples were obtained 0, 15, 30, 60, 120 and 180 min after the injection. Each patient was tested both with SMS 201–995 and placebo. Postmeal glycemic peaks were decreased after SMS 201–995 (119.6 ± 5.4 mg /dl vs 149.1 ± 4.2; p < 0.05) as well as insulin requirements (3.2 ± 0.8 U vs 13.3 ± 1.9; p < 0.01) for the 180 min postprandial period. Similarly, glucagon level was reduced 30 min postprandially (24 ± 6 pg / ml vs 59 ± 24; p < 0.05) and so GH level only 180 min after lunch (p < 0.05). The premeal injection of SMS decreases postprandial glycemic excursions and the corresponding insulin requirement. The action of SMS 201–995 may be mainly mediated by the suppression of postprandial glucagon peak.