Biokinetics of buccal spray insulin in patients with type 1 diabetes

Metabolism. 2005 Jul;54(7):930-4. Biokinetics of buccal spray insulin in patients with type 1 diabetes. Pozzilli P, Manfrini S, Costanza F, Coppolino G, Cavallo MG, Fioriti E, Modi P. Source Department of Endocrinoplogy and Diabetes, University Campus Bio-Medico, Rome, Italy. [email protected] Abstract OBJECTIVE: To evaluate the metabolic effect of buccal spray insulin compared with subcutaneous regular insulin in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: This study compared plasma glucose, insulin, and C-peptide levels in 18 patients with type 1 diabetes treated with subcutaneous regular or buccal spray insulin on 2 consecutive mornings. On day 1, patients were treated with their usual subcutaneous regular insulin regimens. On day 2, patients received buccal spray insulin. In the morning of both days 1 and 2, patients received a standard meal of 630 kJ. No intermediate or long-acting insulin was administered to patients on the morning of the test. Blood samples were collected for up to 4 hours for biokinetic analysis. In a subset of 3 patients, premeal buccal spray insulin was administered for 2 entire consecutive days. In these patients, glucose levels were monitored using the glucose sensor monitoring system. RESULTS: Overall, there were no statistically significant differences in glucose, insulin, or C-peptide levels measured after administration of subcutaneous vs buccal spray insulin. However, at 90 and 120 minutes after subcutaneous regular insulin administration, significantly higher insulin levels and more prolonged hypoglycemic effect were detected compared with buccal spray insulin administration. In the 3 patients who received 1 day of regular and 2 entire days of buccal spray insulin, no significant differences were observed in glucose levels during the 3 days of glucose sensor monitoring. CONCLUSIONS: Insulin administered via the buccal spray formulation is as effective as the subcutaneous route in lowering blood glucose levels

A case of pheochromocytoma with negative MIBG scintigraphy, PET-CT and genetic tests (VHL included) and a rare case of post-operative erectile dysfunction

BACKGROUND: Pheochromocytoma (Ph) is a rare catecholamine-secreting neuroendocrine tumour that arises from the chromaffin cells of the adrenal medulla. Ph usually presents with symptoms including paroxysmal headache, sweating, palpitations, and hypertension. CLINICAL CASE: During a computed tomography (CT) scan in a normotensive 49-year-old man, an incidentaloma of 4.5 cm was detected. Hypercortisolism was excluded after the dexamethasone suppression test, levels of DHEAS all falling within the normal range. After a 24-h urine collection, normal urinary metanephrines and a 4-fold higher level compared to the normal range of urinary normetanephrines were observed. Cortisoluria levels were within the normal range. Multiple endocrine neoplasia type 2 (MEN 2) was also excluded. Before the adrenalectomy, 123I meta-iodobenzylguanidine scintigraphy (MIBG) and 18F-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG PET)/CT were performed and were both negative. Histological examination confirmed the laboratory diagnosis of Ph. Genetic screening to evaluate the SDHB, SDHD, RET, CDKN1B, and VHL genes was requested in order to test for Von Hippel Lindau disease, but unexpectedly all of these were negative. On follow-up after surgery, the patient presented normal urinary catecholamines. However, after Ph removal, he reported frequent episodes of erectile dysfunction (ED) despite non-use of any antihypertensive medications and in the absence of any other precipitating factors, such as hormonal imbalance. CONCLUSIONS: This is a case report in which, in a normotensive patient with Ph, both MIBG and FDG PET-CT were negative, as were also genetic exams, including VHL, this underlining the difficulties in diagnosing this condition; furthermore, a rare case of ED occurred after surgery

Biomarkers of response to alpha-lipoic acid ± palmitoiletanolamide treatment in patients with diabetes and symptoms of peripheral neuropathy

PURPOSE: To evaluate the effect of oral alpha-lipoic acid (ALA) ± palmitoyl-ethanolamide (PEA) on neuropathic symptoms in patients with diabetic peripheral neuropathy (DPN) and to identify factors related to the efficacy of the treatment. METHODS: This is a retrospective observational pilot study evaluating 49 patients with diabetes and positive Neuropathy Symptoms Score (NSS). Clinical and biochemical variables, including NSS, were compared between untreated patients and patients treated with oral 600 mg/day ALA ± 600 mg/day PEA at baseline (first occurrence of NSS ≥ 3) and at least 2 months after baseline. Number of days between treatment initiation and symptoms' relief and related factors were also investigated. RESULTS: Thirty subjects were treated with ALA ± PEA and 19 subjects did not receive any specific treatment for neuropathy symptoms. Follow-up visits occurred after 98 ± 46 days. NSS significantly decreased in patients treated with ALA ± PEA (5.4 ± 1.3 at baseline vs. 1.7 ± 2.4 at follow-up, p < 0.001), but not in untreated patients (p = 0.164). Subjects treated with ALA ± PEA reported a mean time from treatment initiation to symptoms' relief of 18.4 ± 9.0 days. The number of days of treatment needed for symptoms' relief was inversely related to HDL-cholesterol levels (r = -0.503, p = 0.010) and to eGFR (r = -0.428, p = 0.033), whereas there was no significant relationship between time to symptoms' relief and age, HbA1c, lipid profile and the severity of symptoms at baseline. CONCLUSIONS: This study documents that oral administration of ALA ± PEA helps in controlling neuropathy symptoms in diabetes. Moreover, our data show that higher HDL-c levels and better renal function are associated to a faster therapeutic effect, suggesting them as biomarkers of response to therapy with ALA ± PEA

Antibodies to oxidized insulin improve prediction of type 1 diabetes in children with positive standard islet autoantibodies

BACKGROUND: Antibodies to posttranslationally modified insulin (oxPTM-INS-Ab) are a novel biomarker of type 1 diabetes (T1D). Here, we evaluated whether oxPTM-INS-Ab can improve T1D prediction in children with positive standard islet autoantibodies (AAB). METHODS: We evaluated sensitivity, specificity, accuracy, and risk for progression to T1D associated with oxPTM-INS-Ab and the standard islet AAB that include insulin (IAA), GAD (GADA), and tyrosine phosphatase 2 (IA-2A) in a cohort of islet AAB-positive (AAB+ ) children from the general population (median follow-up 8.8 years). RESULTS: oxPTM-INS-Ab was the most sensitive and specific autoantibody biomarker (74% sensitivity, 91% specificity), followed by IA-2A (71% sensitivity, 91% specificity). GADA and IAA showed lower sensitivity (65% and 50%, respectively) and specificity (66% and 68%, respectively). Accuracy (AUC of ROC) of oxPTM-INS-Ab was higher than GADA and IAA (P = 0.003 and P = 0.017, respectively), and similar to IA-2A (P = 0.896). oxPTM-INS-Ab and IA-2A were more effective than IAA for detecting progr-T1D when used as second-line biomarker in GADA+ children. Risk for diabetes was higher (P = 0.03) among multiple AAB+ who were also oxPTM-INS-Ab+ compared with those who were oxPTM-INS-Ab- . Importantly, when replacing IAA with oxPTM-INS-Ab, diabetes risk increased to 100% in children with oxPTM-INS-Ab+ in combination with GADA+ and IA-2A+ , compared with 84.37% in those with IAA+ , GADA+ , and IA-2A+ (P = 0.04). CONCLUSIONS: Antibodies to oxidized insulin (oxPTM-INS-Ab), compared with IAA which measure autoantibodies to native insulin, improve T1D risk assessment and prediction accuracy in AAB+ children

The utility of assessing C-peptide in patients with insulin-treated type 2 diabetes: a cross-sectional study

Aims We aimed at evaluating residual β-cell function in insulin-treated patients with type 2 diabetes (T2D) while determining for the first time the difference in C-peptide level between patients on basal–bolus compared to those on the basal insulin scheme, considered as an early stage of insulin treatment, together with assessing its correlation with the presence of complications. Methods A total of 93 candidates with T2D were enrolled in this cross-sectional study and were categorized into two groups based on the insulin regimen: Basal–Bolus (BB) if on both basal and rapid acting insulin, and Basal (B) if on basal insulin only, without rapid acting injections. HbA1c, fasting C-peptide concentration and other metabolic parameters were recorded, as well as the patient medical history. Results The average fasting C-peptide was 1.81 ± 0.15 ng/mL, and its levels showed a significant inverse correlation with the duration of diabetes (r = -0.24, p = 0.03). Despite similar disease duration and metabolic control, BB participants displayed lower fasting C-peptide (p &lt; 0.005) and higher fasting glucose (P = 0.01) compared with B patients. Concentrations below 1.09 ng/mL could predict the adoption of a basal–bolus treatment (Area 0.64, 95%CI:0.521–0.759, p = 0.038, sensitivity 45% and specificity 81%). Conclusions Insulin-treated patients with long-standing T2D showed detectable level of fasting C-peptide. Measuring the β-cell function may therefore guide toward effective therapeutic options when oral hypoglycemic agents prove unsuccessful

Treatment of reactive hypoglycemia with the macrobiotic Ma-pi 2 diet as assessed by continuous glucose monitoring: The MAHYP randomized crossover trial

BACKGROUND AND AIMS: Nutritional therapy is recommended for management of reactive hypoglycemia (RH), a condition characterized by hypoglycemia that occurs within four hours after a meal. The macrobiotic Ma-Pi 2 diet improves glycemic control in subjects with type 2 diabetes. We explored the effect of this diet on outcomes in non-diabetic individuals with RH. MATERIALS AND METHODS: Twelve subjects with RH were randomized to the Ma-Pi 2 diet for three days and a control diet for three days in a randomized crossover design. Subjects received snacks on two days out of each three-day period only, and were monitored using continuous glucose monitoring. The 24-h period was divided into daytime (08:00-22:30h [subdivided into 'daytime without snacks' and 'daytime with snacks']) and night-time (22:31-07:59h). The effects of the two diets on the number of RH events (blood glucose 180mg/dL (4.4mmol/L) were determined. RESULTS: There were significantly fewer RH events on the Ma-Pi 2 diet than the control diet during daytime without snacks (-2.5 events; 95% CI: -7.5, 0.0; P=0.022) and daytime with snacks (-4.25 events; 95% CI: -7.5; -2.0; P=0.013) but no difference at night. The percentage of glucose readings in the interval 71-80mg/dL (3.9-4.4mmol/L) was significantly higher on the control diet during daytime with and without snacks (P=0.03 for both), while the percentage of glucose readings in the interval 91-100mg/dL (5.1-5.6mmol/L) was significantly higher on the Ma-Pi 2 diet during daytime without snacks (P=0.02). CONCLUSIONS: The macrobiotic Ma-Pi 2 diet reduced blood glucose excursions during the day, thereby facilitating glycemic control in subjects with RH. The Ma-Pi 2 diet represents an effective nutritional tool for management of RH

Pancreatic scintigraphy with 99mTc-interleukin-2 at diagnosis of type 1 diabetes and after 1 year of nicotinamide therapy

[Epub ahead of print] PMID: 1791827