R. Le Moli

A simplified diagnostic test for ambulatory screening of peripheral diabetic neuropathy

The reliability and reproducibility of Michigan Neuropathy Screening Instrument (MNSI), a recently proposed simple test for ambulatory screening of peripheral diabetic neuropathy (PDN), was evaluated on 80 diabetic patients. MNSI was carried out by two diabetologists and repeated after a week. It consisted of the sum of scores varying from 0 to 1 for each abnormality revealed in foot appearance, achilles reflexes presence and vibratory threshold (VPT) by tuning fork (maximum score = 8). Then patients had to go to neurologist for PDN diagnosis by a quantitative neurological examination and electrophysiological evaluation, the so named Michigan Diabetic Neuropathy Score (MDNS) and the results compared with MNSI score according to one of the two observers. The inter-observer reproducibility of MNSI was 88.75% the within observer reproducibility was 95 and 94%, respectively, for each observer with good correlation between the two measurements (P < 0.001). The MNSI score of 2.5 as a cut-off appeared to be reliable for ambulatory screening of suspected PDN (false positive and false negative = 2.5%; specificity and sensitivity = 75% and 78.6%, respectively). In conclusion MNSI by using 2.5 score as cut-off may be considered a rapid, simple, reproducible and reliable test for rapid ambulatory screening of PDN from the diabetologists.

Long-term octreotide treatment reduced hyperinsulinemia, excess body weight and skin lesions in severe obesity with acanthosis nigricans

A boy affected by severe obesity (kg 117, Body Mass Index 37 kg/m2) and acanthosis nigricans, was treated with octreotide for 150 days (50 μg × three daily subcutaneous administrations). Before treatment the patient showed an exaggerated insulin (IRI) and C-peptide (CPR) response to a standard meal with a lowering in after-meal CPR/IRI molar ratio. During octreotide treatment both IRI and CPR response was reduced but CPR/IRI molar ratio rised after meal indicating an increase in hepatic insulin removal. Body weight and acanthosis nigricans were sharply reduced during treatment and the reduction was still maintained six months after the cessation of therapy. Furthermore, IRI and CPR response, as well as the behaviour of CPR/IRI molar ratio, remained within normal range. In conclusion long-term octreotide treatment has been able to correct hyperinsulinemia and to reduce body weight and acanthosis nigricans.

The tall cell variant of papillary thyroid carcinoma: Clinical and pathological features and outcomes

Background: The tall cell variant (TCV) is a relatively rare variant of papillary thyroid cancer. Since a controversy exists whether or not the TCV has a worse outcome, the aim of our study was to retrospectively compare the clinicopathological features and outcomes in a group of TCV patients and a larger group of patients with classical papillary thyroid carcinoma (cPTC). Subjects and methods: Data from 30 TCV and 293 cPTC patients were analyzed. Among the 293 cPTC, we also selected a “high-risk” cPTC group (no.=103) that was treated with the same protocol used for the TCV patients. All data were managed by Cox analysis. Results: Compared to all cPTC patients, TCV subjects displayed only a significantly higher rate of extrathyroid extension. At multivariate analysis, TCV was not an independent variable for the prediction of a high risk of persistent/recurrent disease. At the last follow-up observation, there was no difference in the disease status between the TCV and all cPTC patients. Moreover, “high-risk” cPTC patients had a significant increase in persistent/recurrent disease. Conclusions: In our study, although the TCV histotype is associated with a higher prevalence of extrathyroid extension, it is characterized by an outcome that is not significantly different from that of all cPTC patients and is more favorable than that of “high-risk” cPTC patients. Only those TCV patients classified as “high risk” based on specific pathological and clinical features, according to current guidelines, should be treated aggressively, such as with a total thyroidectomy, neck lymph node dissection or ablative radioiodine treatment.

Effects of octreotide on glycaemic control, glucose disposal, hepatic glucose production and counterregulatory hormones secretion in type 1 and type 2 insulin treated diabetic patients

We studied the effects of continuous subcutaneous infusion of octreotide (100 micrograms/day for 5 days) on glycaemic values, counterregulatory hormones secretion, hepatic glucose production (HGP) and glucose disposal during an euglycaemic clamp in 7 C-peptide-negative type 1 diabetic patients and 7 C-peptide positive insulin-treated type 2 diabetic patients. In type 1, but not type 2 diabetic patients, octreotide significantly reduced glycaemic values (P < 0.005) and also diminished HGP during an euglycaemic clamp (P < 0.05). However, insulin stimulated global glucose uptake remained unchanged. GH, glucagon, IGF-I, IGFBP-3 levels, were significantly lowered by octreotide in both type 1 and type 2 diabetic patients whereas cortisol and epinephrine remained unmodified. Moreover in type 2 diabetic patients both basal (P < 0.05) and after-meal (P < 0.01) C-peptide secretion was reduced by octreotide. These data point to different metabolic effects of octreotide in type 1 versus type 2 diabetic patients with the drug only being able to reduce glycaemic values and HGP in the former but not in the latter subjects. The failure of octreotide to diminish glycaemic values and HGP in type 2 diabetic patients in spite of its ability to lower GH and glucagon may probably depend on temporary blockage of residual endogenous insulin secretion induced by octreotide administration.

Effect of octreotide on insulin requirement, hepatic glucose production, growth hormone, glucagon and c-peptide levels in type 2 diabetic patients with chronic renal failure or normal renal function

Aim of this study was to investigate whether octreotide, a synthetic somatostatin analogue that inhibits growth hormone, insulin and glucagon secretion and improves glycaemic control in insulin dependent diabetic patients was able to exert similar effects in insulin treated type 2 diabetic patients with chronic renal failure who have high plasma glucagon levels. For this purpose saline or octreotide was randomly administered by continuous subcutaneous infusion (100 mcg/daily) in addition to usual insulin treatment for 5 days to six type 2 insulin treated diabetic patients with chronic renal failure and to six type 2 patients with normal renal function, as a control group. At day 3 of insulin plus saline or insulin plus octreotide treatment, total glucose uptake and hepatic glucose production (HGP) were investigated during an euglycemic clamp; at day 5 GH, glucagon and C-peptide plasma levels were evaluated. Octreotide treatment lowered endogenous insulin secretion (evaluated by C-Peptide levels assay), GH and glucagon in all patients, but caused a significant reduction of daily insulin requirement (32 +/- 14 I.U. vs 41 +/- 19 I.U., P<0.02) only in patients with renal failure. HGP was significantly (P<0.05) lowered in patients with renal failure but glucose uptake remained unchanged. The lowering effect of octreotide on insulin requirement in diabetic patients with renal failure in spite of the contemporaneous inhibition on insulin secretion could be explained on the basis of the greater reduction of glucagon levels which are very elevated in these patients as compared to patients with normal renal function. The lowering of glucagon could decrease HGP and, consequently, insulin requirement.

Effect of octreotide on blood glucose and counterregulatory hormones in insulin-dependent diabetic patients: the role of dose and route of administration

Objective: The role of the dose and route of administration of octreotide in addition to insulin on daily blood glucose, growth hormone, glucagon, cortisol and adrenaline profiles in 7 insulin-dependent diabetic patients have been studied. Octreotide was administered either as multiple subcutaneous injections (50 μg three times daily, total dose 150 μg) or by continuous subcutaneous infusion of lower 62.5 μg 24/h and 112.5 μg 24/h. Results:Blood glucose and growth hormone concentrations were lowered by octreotide in a similar manner regardless of the route of administration and dose. Glucagon concentrations at 12 and 16 h were reduced by all octreotide doses, but fasting at 20, 24 and 04 h concentrations were lowered only by 113 μg given by continuous infusion. Cortisol and adrenaline concentrations were not modified. Conclusions:Thus, low doses of octreotide administered by continuous infusion in addition to standard insulin treatment displayed the same hypoglycaemic effect as larger doses given by multiple injections without causing adverse-effects or hypoglycaemic episodes.

Different effects of octreotide by continuous night infusion at increasing rate or by evening injections at different times on morning hyperglycemia and growth hormone levels in insulin-dependent diabetic patients

The effect of octreotide on morning hyperglycemia and GH levels was evaluated in eight insulin-dependent diabetic patients. Octreotide (50 mcg) was administered through subcutaneous injections at different hours (20: 00, 22: 00 and 24: 00h) or through continuous subcutaneous night infusion from midnight to 08: 00 at increasing rate between 03: 00 and 08: 00h. After octreotide injection at midnight we noticed a sharp decrease of both glycemia (p<0.005) and GH (p<0.05) at 04: 00h, but not at 08: 00h. Only the night continuous infusion at increasing rate was able to reduce glycemia and GH at 04: 00 and at 08: 00h (p<0.001 and p<0.01 respectively). The injections of octreotide at 20: 00 and 22: 00h lowered GH values at 24: 00h (p<0.01 and p<0.05 vs insulin alone) but did not show any signicant effect on blood glucose levels and GH at 04: 00 and 08: 00h. In conclusion, only the continuous subcutaneous night infusion of octreotide at increasing rate during the last hours of the night was able to reduce simultaneously morning hyperglycemia and GH levels in insulin-dependent diabetic patients, whereas evening subcutaneous injections at different times did not show any appreciable effect.

Lack of pharmacological effect of subcutaneous octreotide in an insulin-dependent diabetic patient: Reversal after mixing with aprotinin

Octreotide, a synthetic analogue of somatostatin, may improve metabolic control and reduce GH and glucagon levels in insulin-dependent diabetic patients. We report hereto the case of an insulin-dependent diabetic patient in whom the subcutaneous continuous infusion of octreotide (150 μg/daily for six days) resulted ineffective on blood glucose levels, GH and glucagon. However, when octreotide was administered mixed together with aprotinin — an inhibitory of proteolytic enzymes (10.000 I.U. daily), it had lowering effect on blood glucose levels, GH and glucagon. We suggest the possibility that a local subcutaneous enzymatic degradation of octreotide may have occurred and that this degradation was blocked by aprotinin.