Carlo Coscelli

A Multicenter Study on the Prevalence of Diabetic Neuropathy in Italy

OBJECTIVE The prevalence of neuropathy, a common complication of diabetes, was determined in diabetic patients recruited from 109 outpatient diabetes clinics in Italy. RESEARCH DESIGN AND METHODS Neuropathy was diagnosed using the Diabetic Neuropathy Index (DNI), a standardized examination developed for use in the outpatient setting. A total of 8,757 diabetic patients were studied, 51.2% men and 48.8% women, with average and median ages of 56 and 58 years, respectively. RESULTS Of the 8,757 patients, 32.3% had neuropathy, defined as a positive score of > 2 points on the DNI. A total of 2,033 (49.6% men and 50.4% women) were administered the Diabetic Neuropathy Score (DNS), the second component of the screening program, by a neurologist. This component consists of a quantitative neurological examination and nerve conduction studies that together provide a summated score. A total of 335 patients (16.5%) were not neuropathic, and 395 (19.4%) had borderline, 453 (22.3%) mild, 592 (29.1%) moderate, and 258 (12.7%) severe neuropathy. The concordance between a positive score on the DNI and a DNS indicating neuropathy was 83.5%. The severity of neuropathy increased with both age and disease duration. Of patients with neuropathy, 64.1% had an average age between 58 and 59 years with a disease duration between 12.4 ± 8.4 years (mild neuropathy) and 15.6 ± 9.7 years (severe neuropathy). CONCLUSIONS Neuropathy is a common complication of diabetes and, in this study, was present in 32.3% of all patients. An increased awareness of the high prevalence of neuropathy can lead to early therapeutic intervention and possible prevention of later neuropathic complications, such as infection and foot ulcers.

Decreased hepatic insulin extraction in subjects with mild glucose intolerance

The fact that hyperinsulinemia occurs in simple obesity and mild glucose intolerance has been well established. Altered hepatic insulin extraction may influence the levels of circulating hormone. The simultaneous measurement of insulin and C-peptide concentrations in peripheral blood enables an in vivo estimation of hepatic insulin removal. To evaluate hepatic insulin extraction, insulin and C-peptide responses to oral glucose were studied in 176 obese and nonobese subjects with normal, impaired, or diabetic glucose tolerance. Insulin levels as well as insulin incremental areas in glucose intolerant subjects were significantly higher than in weight-matched controls. The levels of C-peptide as well as C-peptide incremental areas were only slightly enhanced in subjects with impaired glucose tolerance, whereas they were reduced in subjects with diabetic tolerance. The molar ratios of C-peptide to insulin, both in the fasting state and after ingestion of glucose, as well as the relationship between the incremental areas of the two peptides were used as measures of hepatic insulin extraction. They were significantly reduced in glucose intolerant subjects and, to a lesser extent, in nondiabetic obese subjects. These results indicate that peripheral hyperinsulinemia in subjects with simple obesity or impaired glucose tolerance is a result of both pancreatic hypersecretion and diminished hepatic insulin extraction. In subjects with a more severe degree of glucose intolerance, decreased hepatic insulin removal is the primary cause of hyperinsulinemia.

Relationship between blood pressure and plasma insulin in non-obese and obese non-diabetic subjects

SummaryIn this study, we have measured plasma insulin at fasting and following an oral glucose load and blood pressure after glucose load in 367 (247 non-obese, 120 obese) normotensive and untreated mildly hypertensive subjects. Overall, there was no independent association between fasting plasma insulin levels and blood pressure values. After controlling for age and body weight, a significant relationship between postglucose plasma insulin levels and diastolic blood pressure was found. When non-obese and obese subjects were examined separately, significant relationships were identified between postglucose plasma insulin levels and both systolic and diastolic blood pressure values in the former but not in the latter. A comparison of sex-, age-, and weight-matched hyperinsulinaemic vs normoinsulinaemic subjects showed that the former had significantly higher values of blood pressure only if not obese. These results demonstrate that the plasma insulin response to glucose is independently correlated with blood pressure.

Quality of diabetes care predicts the development of cardiovascular events: results of the AMD-QUASAR study.

OBJECTIVE The QUASAR (Quality Assessment Score and Cardiovascular Outcomes in Italian Diabetes Patients) study aimed to assess whether a quality-of-care summary score predicted the development of cardiovascular (CV) events in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In 67 diabetes clinics, data on randomly selected patients were extracted from electronic medical records. The score was calculated using process and outcome indicators based on monitoring, targets, and treatment of A1C, blood pressure, LDL cholesterol, and microalbuminuria. The score ranged from 0 to 40. RESULTS Overall, 5,181 patients were analyzed; 477 (9.2%) patients developed a CV event after a median follow-up of 28 months. The incidence rate (per 1,000 person-years) of CV events was 62.4 in patients with a score of <15, 41.0 in those with a score between 20 and 25 and 36.7 in those with a score of >25. Multilevel analysis, adjusted for clustering and case-mix, showed that the risk to develop a new CV event was 84% higher in patients with a score of <15 (incidence rate ratio [IRR] = 1.84; 95% confidence interval [CI] 1.29–2.62) and 17% higher in those with a score between 15 and 25 (IRR = 1.17; 95% CI 0.93–1.49) compared with those with a score of >25. Mean quality score varied across centers from 16.5 ± 7.5 to 29.1 ± 6.3. When the score was tested as the dependent variable, it emerged that 18% of the variance in the score could be attributed to setting characteristics. CONCLUSIONS Our study documented a close relationship between quality of diabetes care and long-term outcomes. A simple score can be used to monitor quality of care and compare the performance of different centers/physicians.

Influence of the menstrual cycle on glucose tolerance and insulin secretion

To evaluate the impact of the menstrual cycle on glucose tolerance and insulin secretion, in the present study we have measured the plasma concentrations of glucose, insulin, and C-peptide during a 2-hour oral glucose tolerance test in 110 healthy, nonobese, regularly menstruating women. Fifty-five women were in the follicular phase, and 55 were in the luteal phase of the cycle. The two groups were well matched for age and body weight. Plasma concentrations of glucose, insulin, and C-peptide either in the fasting state or after the oral glucose load did not differ in the two groups. These results suggest that in nondiabetic women the menstrual cycle has no major effect on glucose tolerance and insulin secretion and that the phase of the menstrual cycle should not be considered in programming and interpreting an oral glucose tolerance test.

Lack of effect of intravenous metformin on plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in non-diabetic subjects

A study was carried out to evaluate the acute effect of an intravenous injection of metformin on the fasting plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in 15 non-diabetic subjects. Metformin (1 g) was administered as a bolus in a peripheral vein and blood was sampled 2, 5, 10, 15 and 30 minutes after the drug injection. No significant change in fasting concentration of glucose nor in C-peptide, insulin, glucagon and growth hormone fasting levels was noticed. It is concluded that metformin does not possess an acute direct hypoglycaemic effect in non-diabetic subjects and does not acutely affect the basal activity of endocrine pancreas and pituitary gland in releasing insulin, glucagon and growth hormone.

Importance of premeal injection time in insulin therapy: Humalog Mix25 is convenient for improved post-prandial glycemic control in type 2 diabetic patients with Italian dietary habits

Abstract.We investigated the use, in a short period, of Humalog Mix25 (Mix25) in a twice-daily administration regimen compared to a twice-daily injection therapy with Humulin 30/70 (30/70) in diabetic patients with Italian dietary habits. We studied 33 type 2 diabetic patients aged 59.1±8.1 years, BMI 29.8±2.7 kg/m2, duration of diabetes and insulin therapy of 14.4±9.8 and 4.2±4.6 years, respectively. After a 4-day leadin period of twice-daily human insulin 30/70 treatment, patients were randomized to one of two treatment sequences: (1) a twice-daily regimen with Mix25 just 5 minutes before the morning and evening meals for 12 days, followed by a twicedaily therapy with human insulin 30/70 given 30 minutes before the morning and evening meals for an additional 12 days; or (2) the alternate sequence. Each patient underwent a mixed meal test: Humulin 30/70 was administered 30 minutes before the meal, while Mix25 was given 5 minutes before. The 2-hour post-prandial glucose concentration after breakfast was significantly lower during treatment with Mix25 than with Humulin 30/70 (157±43.2 vs. 180±43.2 mg/dl, p<0.05). The glycemic excursion after dinner on Mix25 treatment was significantly lower than with Humulin 30/70 (12.2±48.01 vs. 35.5±36.92 mg/dl, p<0.05). AUCglucose after Mix25 was lower than after Humulin 30/70. Glycemia after test meal was significantly lower with Mix25 than with Humulin 30/70. Insulin and free insulin concentrations after the test meal were significantly higher with Mix25 in comparison to Humulin 30/70. AUC serum insulin and free insulin curves after Mix25 were significantly higher than after Humulin 30/70 (p=0.028 and p=0.005, respectively). Twice-daily injections of Humalog Mix25, compared to human insulin 30/70 in type 2 diabetic patients with Italian dietary habits, provide improved and lasting post-prandial glycemic control, with the great convenience of the injection just before the meal.

Direct medical costs unequivocally related to diabetes in Italian specialized centers.

This study estimated the resource utilization and direct medical costs in Italian diabetes centers (DCs). Hospital admissions for major chronic complications were not considered since DCs deliver primary care and follow up only complications unequivocally related to diabetes-acute complications and diabetic foot. The multicenter, prospective, observational study involving 31 Italian DCs included a total of 1,910 patients classified into eight prognostic groups by type of diabetes (types 1 and 2), metabolic control (HbA1c >7.5%, HbA1c ≤7.5%) and age (≤60, >60). The average total cost of type 1 diabetes per patient per year ranged from € 762 in group 2 (age ≤60, HbA1c >7.5%) to € 1,060 in group 4 (age >60, HbA1c >7.5%), and that the cost of type 2 diabetes from € 423 in group 5 (age ≤60, HbA1c ≤7.5%) to € 613 in group 8 (age >60, HbA1c >7.5%). The study brought to light the wide variability in the single cost components across clinically defined groups of patients. The cost of diabetes management in the strict sense was significantly affected by the type of diabetes and metabolic control.

Combined sulphonylurea-biguanide therapy for non-insulin dependent diabetics. Metabolic effects of glibenclamide and metformin or phenformin in newly diagnosed obese patients

SummaryFasting, pre-prandial and post-prandial blood glucose levels and blood lactate, blood pyruvate, serum cholesterol, serum triglycerides and body weight were measured in 30 obese, newly diagnosed, non-insulin-dependent diabetics at the end of 4 subsequent periods of different regimens, each lasting for 5 days. In the first period, patients remained on free diet; in the second period, a hypocaloric diet (20 kcal/kg IBW) was followed; in the third period, glibenclamide (2.5 mg 3-times daily) was added to hypocaloric diet. During the last period, the patients were divided into two groups: Group A (15 patients) received, in addition to diet and glibenclamide, phenformin (25 mg 3-times daily) and Group B (15 patients) received, in addition to diet and glibenclamide, metformin (500 mg 3-times daily). Five similar patients served as controls and, at the end of the free-diet period, were put on hypocaloric diet and continued this regimen throughout the study period. The results showed that biguanides allowed...

Possible roles of insulin, glucagon, growth hormone and free fatty acids in the pathogenesis of insulin resistance of subjects with chronic liver diseases

SummaryIn the present investigation, insulin sensitivity and fasting levels of insulin, C-peptide, glucagon, growth hormone and free fatty acids were estimated and correlated in a population of individuals suffering from liver cirrhosis or chronic hepatitis. Insulin sensitivity, assessed by glucose disappearance rate after intravenous bolus injection of insulin, was reduced but not significantly different from controls in subjects with chronic persistent hepatitis, while it was significantly reduced in individuals suffering from chronic active hepatitis or liver cirrhosis. Insulin, glucagon, growth hormone, and free fatty acid fasting levels were higher than in healthy subjects in individuals with liver cirrhosis or chronic active hepatitis but not in subjects with chronic persistent hepatitis. C-peptide concentrations did not differ from controls in subjects with liver disease. Significant negative correlations occurred between coefficients of insulin sensitivity and fasting concentrations of insulin, glucagon, growth hormone and free fatty acids, but not with fasting levels of C-peptide. Positive relationships were present between fasting levels of free fatty acids and both glucagon and growth hormone concentrations. These results show that, unlike subjects with liver cirrhosis and chronic active hepatitis, individuals suffering from chronic persistent hepatitis do not differ from healthy subjects in insulin sensitivity and fasting levels of insulin, glucagon, growth hormone, and free fatty acids. Moreover, they suggest that both hyperinsulinemia and high concentrations of counterregulatory substances might play a role in the pathogenesis of insulin resistance in subjects suffering from chronic liver disease.