Biomedical subjects

C Fanelli

Publications and source records attributed to C Fanelli.

At least 19 recordsLinked to original sources

PubMed2006

A randomized controlled trial to evaluate the efficacy of ultrasound-guided laser photocoagulation for treatment of benign thyroid nodules.

This randomized controlled study was designed to test the efficacy and safety of percutaneous ultrasound (US)-guided laser photocoagulation (PLP) for treatment of subjects with compressive symptoms due to benign thyroid nodules and/or at high surgical risk. Twenty six subjects were randomized to the intervention (no. 13, age 68+/-3 yr, mean+/-SEM) or observation (no. 13, age 71+/-2 yr) groups. In the control group, the volume of nodules did not significantly change over the 30 week period of observation. In the intervention group, median nodule volume at baseline was 8.2 ml (range 2.8-26.9) and was not significantly different from that of the control group. Nodules decreased significantly (p<0.0001) by 22% after 2 weeks (6.5 ml; range 2.4-16.7) and by 44% after 30 weeks (4.6 ml; range 0.69-14.2). Energy given was correlated (p<0.05) with the reduction of thyroid nodule volume. All patients tolerated the treatment well and reported relief from compressive and cosmetic complaints (p<0.05). At the time of enrolment 7/13 (54%) and 6/13 (46%) of patients in the intervention and control groups, respectively, had sub clinical hyperthyroidism. PLP normalized thyroid function at 6 and 30 weeks after treatment. In conclusion, PLP is a promising safe and effective procedure for treatment of benign thyroid nodules in patients at high surgical risk.

Aged↗

PubMed2005

Antioxidant enzymes stimulation in Aspergillus parasiticus by Lentinula edodes inhibits aflatoxin production.

Biosynthesis of aflatoxins, toxic metabolites produced by Aspergillus parasiticus, is correlated to the fungal oxidative stress and cell ageing. In this paper, the mechanism underlying the aflatoxin-inhibiting effect of the Lentinula edodes culture filtrates was studied by analysing their anti-oxidant activity and beta-glucan content. Mushroom beta-glucans are pharmacologically active compounds stimulating anti-oxidant responses in animal cells. L. edodes lyophilised filtrates stimulate A. parasiticus anti-oxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and aflatoxin inhibition was better correlated with beta-glucan content than with anti-oxidant activity of the filtrates. RT-PCR analyses on treated mycelia showed a delay in the activation of aflR, and norA, genes of aflatoxin cluster and a synchronous activation of hsf2-like, a homologue of a yeast transcription factor involved in oxidative stress responses. The first evidence of hsf2-like in A. parasiticus and its activation during aflatoxin biosynthesis is reported. L. edodes filtrates could play a role as external stimulus affecting the anti-oxidant status in the fungal cell that, in turn, leads to aflatoxin inhibition. In the fungal cell, beta-glucans present in the filtrates could stimulate the activation of transcription factors related to anti-oxidant response and anti-oxidant enzyme activity with a contemporaneous delay of aflatoxin genes transcription, which led to a marked reduction of aflatoxin production. This research suggests new perspectives to set suitable strategies against aflatoxins and L. edodes could be considered a promising tool.

Aflatoxins↗

PubMed2004

Meal intake similarly reduces circulating concentrations of octanoyl and total ghrelin in humans.

UNLABELLED: ABSTRACT. Several data show that meal intake and nutritional status regulate circulating ghrelin concentrations in humans. Ghrelin mainly circulates in two different forms: octanoyl and des-octanoyl ghrelin. Most circulating ghrelin is des-octanoyl ghrelin which is considered inactive because it lacks endocrine activity. However, recent evidence suggests that des-octanoyl ghrelin exerts biological activity such as stimulation of adipogenesis, cardiovascular effects and control of cell growth. In healthy humans, although the total ghrelin concentration is known to peak before meals and to be reduced by food intake, no data are available about the octanoyl ghrelin response in the absorptive state. Therefore, after an overnight fast, we compared the effects of a mixed meal ingestion (meal study) or of additional 240 min fasting (control study) on plasma concentrations of octanoyl and total ghrelin in 6 healthy subjects (body mass index: 23 +/- 0.7). At baseline, octanoyl-ghrelin accounted for 3.15 +/- 0.2% of total circulating ghrelin without differences between the two sessions. A similar ratio was maintained in the absorptive state with no differences between the studies and basal values. Compared with control, meal intake significantly suppressed (nadir at 90 min) octanoyl and total ghrelin by 38 +/- 3 and 40 +/- 3% of basal values, respectively. In the meal study, multivariate analysis of variance showed that serum insulin best predicted plasma octanoyl-ghrelin concentrations accounting for 97% of its variation (r2 = -0.97,p = 0.0016). IN CONCLUSION: in healthy humans, octanoyl-ghrelin represents about 3-4% of total circula-ting ghrelin and this ratio is closely maintained in post-absorptive and absorptive states.

Adult↗

PubMed2003

Circulating ghrelin levels of visceral obese men are not modified by a short-term treatment with very low doses of GH replacement.

Ghrelin, the endogenous ligand for the GH secretagogue-receptor (GHS-R), in addition to its GH-releasing action, has orexigenic and adipogenic properties. These characteristics make ghrelin a potential hormone involved in the pathogenesis of obesity. Ghrelin levels are decreased in obese humans and it is unknown whether this decrease is responsible for the blunted GH secretion reported in visceral obesity. Since only few data are available on the potential feedback regulation by GH on systemic ghrelin concentrations, it remains to be established whether the correction of circulating GH concentrations in obese individuals affects ghrelin concentrations. To answer this question, we measured plasma ghrelin levels after a week of administration of low doses of recombinant human GH (rhGH) in a randomized, double-blind, placebo (PL)-controlled trial. This study was originally designed to evaluate the effects of GH replacement on lipid kinetics in visceral obese men. Six adult men with abdominal/visceral obesity (age 42+/-3 yr, body weight 107 +/- 10 kg, BMI 33 +/- 1 kg/m2, waist circumference 111 +/- 3 cm, mean +/- SE) were evaluated in the basal state (BS) and after one week of treatment with subcutaneous bedtime injections of either PL, 2.5 (GH2.5) or 3.3 (GH3.3) pg/kg/die of rhGH. In comparison to BS either PL, GH2.5 or GH3.3 did not significantly modify circulating ghrelin concentrations (p = 0.77). In contrast, a significant increase of serum GH (p = 0.0028), IGF-I (p = 0.0033) and whole body rate of lipolysis (p = 0.038, GH2.5; p = 0.009, GH3.3) occurred, in comparison to BS or PL, after GH2.5 and GH3.3, without differences between the two treatments. These data demonstrate that in abdominal/visceral obese men a short-term treatment with very low doses of rhGH replacement, sufficient to augment the rate of lipolysis, do not modify circulating ghrelin levels.

Adult↗

PubMed2003

Genetic diversity and population structure of the Italian fungi belonging to the taxa Pleurotus eryngii (DC.:Fr.) Quèl and P. ferulae (DC.:Fr.) Quèl.

A study using allozymes and PCR fingerprinting was conducted to estimate the genetic diversity of Italian populations of two economically important cultivated fungal taxa, Pleurotus eryngii and P. ferulae. Very little is known about the genetic diversity distribution pattern of these taxa. Heterozygote deficiency was observed at few loci; in fact the inbreeding coefficients were not high, which demonstrates that mechanisms restrain the inbreeding act at the local level. Estimates of genetic differentiation indicated a pattern of greater variation within, rather than between, populations. These results were supported by AMOVA analysis, which attributed a low proportion of the total genetic variation to large geographical scale divergence, and indicated that most of the genetic diversity was because of differences within populations. This distribution pattern of genetic variation of P. eryngii and P. ferulae populations seems to be the result of high gene flow, by efficient basidiospore dispersal, and outcrossing mechanisms, which restrain inbreeding within populations.

DNA Fingerprinting↗

PubMed2001

Comparison of PRE-dilatation vs direct stenting in coronary treatment using the Medtronic AVE S670 Coronary Stent System (the PREDICT trial).

Current stent delivery systems make primary stenting (stent placement without predilatation) possible, but few controlled trials have been performed to evaluate the success, safety, cost saving, and potential benefit of this approach in reducing late restenosis. The Comparison of PRE-Dilatation Versus Direct Stenting In Coronary Treatment using the Medtronic AVE S670 Coronary Stent System trial was a 399-patient study comparing results with the Medtronic-AVE S670 stent to objective performance criteria based on prior approved stents, with subrandomization to direct stenting versus stenting after balloon predilatation. Overall, results with the S670 stent showed excellent success and safety, with delivery success of 99%, a 14-day adverse event rate of 6.8% (including 6.5% non-Q-wave myocardial infarction), and favorable angiographic (20%) and clinical (12%) restenosis rates. Direct stenting was successful in 92% of cases, with a 99.5% secondary success rate including additional pretreatment of initially unsuccessful direct-stenting attempts, and no increase in complications. There were modest ( approximately 10%) savings in fluoroscopy time, contrast use, and a decrease in angioplasty balloon use (0.6 vs 1.3 balloons/case), but no reduction in clinical or angiographic restenosis. Patients treated later in the study, with a device that had less balloon extension beyond the edges of the stent, had slightly lower angiographic restenosis rates (19% vs 23%). In conclusion, the S670 stent showed excellent overall performance. Although direct stenting was safe and highly successful, it offered only modest cost savings, and no reduction in late restenosis compared with stenting after predilatation.

Catheterization↗

PubMed2001

Oxidative stress, growth factor production and budding in potato tubers during cold storage.

In order to verify the role played by oxidation in the budding of potato tubers (Solanum tuberosum L. cv. Kennebec), the physiological events occurring below bud at 4 degrees C have been studied for a period of 6 months. The low temperature storage induced an increase in the degree of unsaturation and a decrease in the ratio of saturated/unsaturated fatty acids of membrane polar lipids with a subsequent increase of lipid hydroperoxides (LOOH). Cold stress increased both enzymatic antioxidative activities (superoxide dismutase, SOD, E.C.1.15.1.1; catalase, CAT, E.C.1.11.1.6), and alpha-tocopherol levels thus protecting membrane's polyunsaturated lipids. Between 0 and 15 days of storage SOD/CAT ratio, alpha-tocopherol, LOOH levels and the degree of lipid unsaturation showed strong variations. After 30 to 120/150 days the antioxidative system seemed to reach a homeostasis different from that of time 0, accompanied by a constant increase of indole-3-acetic acid (IAA) after 60 days. The antioxidative system, after 150 days, lost its efficiency while LOOH levels were maintained higher than time 0 and IAA concentration was sufficient to allow sprouting.

Catalase↗

PubMed2000

Solid-state (13)C CP MAS NMR spectroscopy of mushrooms gives directly the ratio between proteins and polysaccharides.

The solid-state (13)C CP MAS NMR technique has the potential of monitoring the chemical composition in the solid state of an intact food sample. This property has been utilized to study mushrooms of different species (Pleurotus ostreatus, Pleurotus eryngii, Pleurotus pulmunarius, and Lentinula edodes), already characterized by chemical analyses for protein and dietary fiber components. Solid-state (13)C CP MAS NMR spectroscopy reveals a large difference in the ratio between the glucidic and the proteic resonances probably depending on the mushroom species. An accurate inspection by model compounds and suitable mixtures of proteins and saccharides gives a methodology to interpret these experimental data. A good correlation (R(2) = 0.93; R(2) = 0.81) has been obtained by comparing the NMR data with the results of the chemical analyses. The results suggest the possibility to perform a taxonomic study and/or a nutritional study on the basis of the ratio between protein and polysaccharide levels determined by NMR or chemical methodologies.

Agaricales↗

PubMed2000

Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro.

To compare the pharmacokinetics/dynamics of the long-acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-peptide-negative type 1 diabetic patients were studied on four occasions during an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U/kg glargine or NPH insulin (random sequence, crossover design). On two subsequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U x kg(-1) x 24 h(-1)) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of IV insulin >50%) was earlier with NPH (0.8 +/- 0.2 h), CSII (0.5 +/- 0.1 h), and ultralente (1 +/- 0.2 h) versus glargine (1.5 +/- 0.3 h) (P < 0.05) (mean +/- SE). End of action (defined as an increase in plasma glucose >150 mg/dl) occurred later with glargine (22 +/- 4 h) than with NPH (14 +/- 3 h) (P < 0.05) but was similar with ultralente (20 +/- 6 h). NPH and ultralente exhibited a peak concentration and action (at 4.5 +/- 0.5 and 10.1 +/- 1 h, respectively) followed by waning, whereas glargine had no peak but had a flat concentration/action profile mimicking CSII. Interindividual variability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in different treatments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultralente are both peak insulins. Duration of action of ultralente is greater, but intersubject variability is also greater than that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mimics CSII, the gold standard of basal insulin replacement.

Adult↗

PubMed2000

Early physiological and cytological events induced by wounding in potato tuber.

The response of potato tuber (Solanum tuberosum L. cv. Kennebec) to mechanical wounding was investigated at different times. Changes in the levels of indole-3-acetic acid (IAA), polyunsaturated fatty acids (PUFAs) and lipid hydroperoxides (LOOHs) were monitored up to 120 min after wounding and related to the cytological events occurring up to 24 h. Twenty minutes after injury, an increase in IAA and LOOH levels and a decrease in the levels of PUFAs was observed. Wounding induced mitoses in differentiated (parenchyma) cells starting at 120 min, and promoted an increase of mitotic activity in the meristematic cells (procambium and bud dome), after 360 min. The inhibition of the increase in LOOHs and IAA by lipoxygenase (LOX) inhibitors, as well as the ability of in vitro peroxidated linoleic acid to enhance IAA production, suggest a close relationship among lipoperoxidation, IAA and mitotic activity in the response of potato tuber cells to injury, resulting in a specific growth response, i.e. bud growth and periderm formation.

Fatty Acids, Unsaturated↗

PubMed2000

Sertoli cell-induced reversal of adult rat pancreatic islet beta-cells into fetal-like status: potential implications for islet transplantation in type I diabetes mellitus.

BACKGROUND: Clinical success of pancreatic islet allograft (TX) for the therapy of diabetes mellitus is hampered by several pitfalls, primarily including the restricted availability of donor tissue and the immune- and/or non-immune-related TX's early loss, with the latter not necessarily being prevented by the host's general immunosuppression. Finally, adult islet beta-cells normally exhibit minimal proliferation capacity, which would not permit restoration of an eventually declining TX mass. METHODS: To address the limited beta-cell growth capacity, we have examined whether in vitro co-culturing adult rat islets (I) with prepubertal homologous Sertoli cells (SC) would stimulate I beta-cell expansion. SC-derived effects on the islets were studied in vitro, both morphologically (confocal laser microscopy) and functionally (glucose-stimulated insulin release). We have also preliminarily examined the in vivo impact of microencapsulated SC + I co-cultures on TX in diabetic mice. RESULTS: In vitro, we observed that SCs promoted significant beta-cell replication, as I beta-cell mitotic activity increased from 1% to greater than 8%, which coincided with the adult elements reversing into fetal-like status. This finding was coupled with significantly greater insulin release either in basal or in response to glucose, as compared with controls. CONCLUSIONS: Addition of SC to islets promotes reversal of the adult beta-cell elements into fetal-like conditions, thereby providing a new, potentially powerful tool that could significantly enhance the functional performance of islet TX in diabetic recipients.

Animals↗

PubMed1999

Magnetic fields increase cell survival by inhibiting apoptosis via modulation of Ca2+ influx.

Static magnetic fields with intensities starting from 6 gauss (6x10(-4) tesla, T) were found to decrease in an intensity-dependent fashion, reaching a plateau at 6 x 10(-3) T, the extent of cell death by apoptosis induced by several agents in different human cell systems. This is not due to a change in the mode of cell death (i.e., to necrosis) or to a delay of the process itself; rather, the presence of magnetic fields allows the indefinite survival and replication of the cells hit by apoptogenic agents. The protective effect was found to be mediated by the ability of the fields to enhance Ca2+ influx from the extracellular medium; accordingly, it was limited to those cell systems where Ca2+ influx was shown to have an antiapoptotic effect. Magnetic fields thus might interfere with human health by altering/restoring the equilibrium between cell death and proliferation; indeed, the rescue of damaged cells may be the mechanism explaining why magnetic fields that are not mutagenic per se are often able to increase mutation and tumor frequencies.

Animals↗

PubMed1999

Glutathione depletion causes cytochrome c release even in the absence of cell commitment to apoptosis.

We demonstrate here that the release of mature cytochrome c from mitochondria is a cellular response to the depletion of glutathione, the main intracellular antioxidant, independently from the destiny of the cells, i.e., apoptosis or survival. On the one hand, cytosolic cytochrome c was detected in cells where the inhibition of glutathione synthesis led to glutathione depletion without impairing viability or in tight concomitance with glutathione depletion prior to puromycin-induced apoptosis. Removal of the apoptogenic agent prior to apoptosis, but after glutathione extrusion and cytochrome c release, led to recovery of preapoptotic cells, which resume healthy features, i.e., restoration of normal glutathione levels and disappearance of cytosolic cytochrome c. On the other hand, in an example of apoptosis occurring without glutathione depletion, no translocation of cytochrome c from mitochondria to cytosol was detected. Unlike the other instances of apoptosis, in this case caspase 3 was not activated, thus suggesting the following oxidant-related apoptotic pathway: glutathione depletion, cytochrome c release, and caspase 3 activation. These results show that cytochrome c release is not a terminal event leading cells to apoptosis, but rather is the consequence of a redox disequilibrium that, under some circumstances, may be associated with apoptosis.

Apoptosis↗

PubMed1998

Rescue of cells from apoptosis by inhibition of active GSH extrusion.

Cells induced to apoptosis extrude glutathione in the reduced form concomitantly with (U937 cells) or before (HepG2 cells) the development of apoptosis, much earlier than plasma membrane leakage. Two specific inhibitors of carrier-mediated GSH extrusion, methionine or cystathionine, are able to decrease apoptotic GSH efflux across the intact plasma membrane, demonstrating that in these cell systems GSH extrusion occurs via a specific mechanism. While decreasing GSH efflux, cystathionine or methionine also decrease the extent of apoptosis. They fail to exert anti-apoptotic activity in cells previously deprived of GSH, indicating that the target of the protection is indeed GSH efflux. The cells rescued by methionine or cystathionine remained viable after removal of the apoptogenic inducers and were even able to replicate. This shows that a real rescue to perfect viability and not just a delay of apoptosis is achieved by forcing GSH to stay within the cells during apoptogenic treatment. All this evidence indicates that extrusion of reduced glutathione precedes and is responsible for the irreversible morphofunctional changes of apoptosis, probably by altering the intracellular redox state without intervention of reactive oxygen species, thus giving a rationale for the development of redox-dependent apoptosis under anaerobic conditions.

Apoptosis↗

PubMed1997

Late post-prandial hypoglycaemia as the sole presenting feature of secreting pancreatic beta-cell adenoma in a subtotally gastrectomized patient.

In this paper we describe for the first time late post-prandial hypoglycaemia as the sole presenting feature of an insulinoma in a patient who had previously undergone subtotal gastrectomy. The symptoms of hypoglycaemia always occurred 1-3 h after meals, not in the fasting state. Because of the history of gastrectomy and because post-prandial hypoglycaemia was reproduced by an oral glucose tolerance test, the diagnosis of reactive hypoglycaemia was made. Eighteen months later a fasting test was performed: venous plasma glucose decreased from 3.8 mmol/l to 2.7 mmol/l between 14 and 20 h of fast while plasma immunoreactive insulin did not decrease and plateaued at 185 pmol/l. Plasma C-peptide (0.9 nmol/l) and proinsulin (70 pmol/l, split 64, 65) were also elevated. All islet hormones increased in response to i.v. glucose and were suppressed after diazoxide. Although pre-operative procedures were negative in localizing an insulinoma, the patient underwent an operation and an insulinoma was detected at the body level of the pancreas. Thus, insulinoma should be considered in the differential diagnosis of reactive hypoglycaemia in gastrectomized patients. Response of islet hormones to glucose and their suppression by diazoxide are evidence of a secreting insulinoma even in the absence of preoperative localization of the pancreatic adenoma.

Blood Glucose↗

PubMed1997

Long-term intensive therapy of IDDM patients with clinically overt autonomic neuropathy: effects on hypoglycemia awareness and counterregulation.

To test the hypothesis that hypoglycemia unawareness and impaired counterregulation are reversible after meticulous prevention of hypoglycemia in IDDM patients with diabetic autonomic neuropathy (DAN), 21 patients (8 without DAN [DAN-]; 13 with DAN [DAN+]; of the latter, 7 had orthostatic hypotension [DAN+PH+] and 6 did not [DAN+PH-]) and 15 nondiabetic subjects were studied during stepped hypoglycemia (plateau plasma glucose decrements from 5.0 to 2.2 mmol/l) before and 6 months after prevention of hypoglycemia (intensive therapy). After 6 months, frequency of mild hypoglycemia decreased from approximately 20 to approximately 2 episodes/patient-month while HbA1c increased from 6.2 +/- 0.3 to 6.9 +/- 0.2% (P < 0.05). Responses of adrenaline improved more in DAN- patients (from 1.17 +/- 0.12 to 2.4 +/- 0.22 nmol/l) than in DAN+PH- (from 0.75 +/- 0.25 to 1.56 +/- 0.23 nmol/l) and DAN+PH+ patients (from 0.80 +/- 0.24 to 1.15 +/- 0.27 nmol/l, P < 0.05) but remained lower than in nondiabetic subjects (4.9 +/- 0.37 nmol/l, P < 0.05), whereas glycemic thresholds normalized only in DAN-, not DAN+. Autonomic symptoms of hypoglycemia improved but remained lower in DAN- (6.2 +/- 0.6) than in nondiabetic subjects (8.1 +/- 1.1) and lower in DAN+PH+ (4 +/- 0.8) than in DAN+PH- subjects (5.1 +/- 0.8, P < 0.05), whereas neuroglycopenic symptoms normalized (NS). Cognitive function deteriorated less before than after prevention of hypoglycemia (P < 0.05). Thus, intensive therapy with emphasis on preventing hypoglycemia reverses hypoglycemia unawareness in DAN+ patients despite marginal improvement of adrenaline responses, results in low frequency of hypoglycemia despite impaired counterregulation, and maintains HbA1c in the range of intensive therapy. We conclude that DAN, long IDDM duration per se, and antecedent recent hypoglycemia contribute to different extents to impaired adrenaline responses and hypoglycemia unawareness.

Adult↗

PubMed1997

A pharmacodynamic study of morphine and its glucuronide metabolites after single morphine dosing in cancer patients with pain.

Eleven morphine naïve patients with cancer-related pain were given a single dose of either intravenous morphine (n = 5) or oral morphine (n = 6). Blood sampling was performed over a 24-hr period and serial pain assessments were made using a categorical scale. Plasma samples were analyzed for morphine, morphine-6-glucuronide (M-6-G), morphine-3-glucuronide (M-3-G), and normorphine using high-performance liquid chromatography. In neither the intravenous nor oral group was there a correlation between analgesia duration and the half-lives of morphine and M-6-G. There was no correlation between the time to peak analgesia and time to peak concentration for morphine or M-6-G. There was no significant difference in absolute concentrations of M-6-G or M-3-6 nor in the ratio of M-3-G to M-6-G at peak analgesia versus relapse.

Administration, Oral↗

PubMed1996

Long-term intensive insulin therapy in IDDM: effects on HbA1c, risk for severe and mild hypoglycaemia, status of counterregulation and awareness of hypoglycaemia.

UNLABELLED: The present studies were designed to assess the percentage of HbA1c, frequency, and awareness of hypoglycaemia (H) during long-term intensive therapy (IT) of insulin-dependent diabetes mellitus (IDDM). From 1981 to 1994, 112 IDDM patients were on IT. HbA1c was 7.17 +/- 0.16% (non-diabetic subjects 3.8-5.5%), the frequency of severe H 0.01 +/- 0.009 episodes/patient-year, frequency of mild symptomatic H 35.6 +/- 2.9 episodes/patient-year. IDDM patients with HbA1c < or = 5.5% (Group I, n = 10), between 6.1-7.0% (Group II, n = 12), and > or = 7.6% (Group III, n = 11) were studied to assess responses of counterregulatory hormones, symptoms and cognitive function during experimental, stepped H. Compared to 18 non-diabetic subjects, Group I exhibited high thresholds (plasma glucose had to decrease more than normal to evoke responses), and impaired responses of adrenaline, unawareness of H and delayed onset of cognitive dysfunction at the lowest glycaemic plateau (2.3 mmol/l). Group II had normal thresholds and responses, whereas Group III had low thresholds. Frequency of mild H was higher in Group I (54.5 +/- 1.9 episodes/patient-year) than in Group II and III (33.7 +/- 3.5 and 20.4 +/- 2.5 episodes/patient-year, respectively, p < 0.001) and correlated with percentage of HbA1c (r = -0.82). IN CONCLUSION: IT can maintain near-normal HbA1c and is compatible with low frequency of severe H. However, if HbA1c is less than 6.0%, mild, symptomatic H is excessively frequent and causes impaired counterregulation and H unawareness. Efforts should be made not only to maintain HbA1c < or = 7.0%, but also to prevent, recognize and reverse iatrogenic H unawareness during long-term IT of IDDM by maintaining HbA1c > 6.0%.

3-Hydroxybutyric Acid↗