Deep tissue biopsy vs. superficial swab culture monitoring in the microbiological assessment of limb-threatening diabetic foot infection.

AIMS: The results of ulcer swabbing vs. deep tissue biopsy have been compared prospectively in 29 diabetic patients with limb-threatening foot infection, to investigate the effectiveness and reliability of each method, and to evaluate whether any of the two could be more suitable for the microbiological follow-up of severe lesions. METHODS: Microbiological samples were collected by using both methods at fixed intervals after therapy commencement (i.e. at day 0, 7, 14, and 30). Statistical comparison was performed between the results of each sampling procedure after the end of follow-up. RESULTS: At enrolment, the mean number of isolates per patient was 2.34 by swabbing and 2.07 by tissue biopsy sampling; the rate of isolation for anaerobes with the two methods was 35% and 25%, respectively; no statistical differences could be observed between the two procedures in terms of either species or frequency of isolation. Anaerobic species were never detected after the first 2 weeks of appropriate treatment, and those ulcers which were still active at day 30 yielded almost exclusively Gram-positive bacteria. At the end of follow-up, deep tissue cultures appeared to exhibit a higher diagnostic sensitivity with respect to swabs. CONCLUSIONS: Swabbing and deep tissue cultures appear to be equally reliable for the initial monitoring of antimicrobial treatment in severe diabetic foot infection. However, our experience seems to suggest that deep tissue might be more sensitive than swabbing for monitoring those isolates that have been selected for antibiotic resistance, i.e. those from ulcers that are still active after 30 days of treatment.

Randomized prospective controlled trial of recombinant granulocyte colony-stimulating factor as adjunctive therapy for limb-threatening diabetic foot infection.

Adult diabetic patients admitted to our Diabetes Center from September 1996 to January 1998 for severe, limb-threatening foot infection were consecutively enrolled in a prospective, randomized, controlled clinical study aimed at assessing the safety and efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF) (lenograstim) as an adjunctive therapy for the standard treatment of diabetic foot infection. Forty patients, all of whom displayed evidence of osteomyelitis and long-standing ulcer infection, were randomized 1:1 to receive either conventional treatment (i.e., antimicrobial therapy plus local treatment) or conventional therapy plus 263 microg of G-CSF subcutaneously daily for 21 days. The empiric antibiotic treatment (a combination of ciprofloxacin plus clindamycin) was further adjusted, when necessary, according to the results of cultures and sensitivity testing. Microbiologic assessment of foot ulcers was performed by both deep-tissue biopsy and swab cultures, performed at enrollment and on days 7 and 21 thereafter. Patients were monitored for 6 months; the major endpoints (i.e., cure, improvement, failure, and amputation) were blindly assessed at weeks 3 and 9. At enrollment, both patient groups were comparable in terms of both demographic and clinical data. None of the G-CSF-treated patients experienced either local or systemic adverse effects. At the 3- and 9-week assessments, no significant differences between the two groups could be observed concerning the number of patients either cured or improved, the number of patients displaying therapeutic failure, or the species and number of microorganisms previously yielded from cultures at day 7 and day 21. Conversely, among this small series of patients the cumulative number of amputations observed after 9 weeks of treatment appeared to be lower in the G-CSF arm; in fact, only three patients (15%) in this group had required amputation, whereas nine patients (45%) in the other group had required amputation (P = 0.038). In conclusion, the administration of G-CSF for 3 weeks as an adjunctive therapy for limb-threatening diabetic foot infection was associated with a lower rate of amputation within 9 weeks after the commencement of standard treatment. Further clinical studies aimed at precisely defining the role of this approach to this serious complication of diabetes mellitus appear to be justified.

A comparison of preconstituted, fixed combinations of low-dose glyburide plus metformin versus high-dose glyburide alone in the treatment of type 2 diabetic patients.

In the present study we assessed and compared the effectiveness and safety of preconstituted, fixed, combinations of low-dose glyburide plus metformin with higher-dose glyburide monotherapy in patients with type 2 diabetes. This randomized, double-blind, cross-over study comprised 40 patients. After a 30-day run-in period of dietary treatment, patients received combined glyburide (5, 7.5 or 10 mg/day) and metformin (800, 1,200 or 1,600 mg/day) as preconstitued, fixed combinations, or glyburide alone (5, 10 or 15 mg/day). The dose was increased stepwise so as to have 1 (T1), 2 (T2) and 3 (T3) months of treatment for any given regimen (6 months in total). After 2 weeks of washout (T4), the groups were then crossed over (T5, T6, T7 periods). Body weight, fasting plasma glucose, HbA(1c), blood lactate, total cholesterol and HDL-cholesterol, and triglycerides were measured at the beginning and end of T1 and T5, and end of T2, T3, T6 and T7; postprandial plasma glucose, fasting and postprandial plasma insulin and C-peptide were evaluated at the beginning of T1 and T5, and end of T3 and T7. At these latter time points additional assessments included routine clinical chemistry measurements, ECG, and ophthalmoscopic examination. Statistical analysis was performed by the paired Student's t-test and analysis of variance for cross-over studies. Thirty-three patients completed the study. Fasting plasma glucose, postprandial plasma glucose and HbA(1c) levels improved significantly during combined treatment with glyburide at lower doses plus metformin. This effect was achieved without any major change of insulin and C-peptide concentrations. Circulating lactate concentrations increased during the regimen including metformin, but they remained well within the reference values for normal subjects. Plasma total cholesterol and triglycerides levels remained substantielly unchanged throughout the study, whereas HDL-cholesterol concentrations increased slightly, but significantly, with glyburide plus metformin therapy. Routine clinical chemistry measurements, ECG and ophthalmoscopic examinations did not change during the study. These results demonstrate that improved metabolic control can be achieved with preconstituted, fixed combinations of low-dose glyburide plus metformin in patients with type 2 diabetes, compared to higher doses of the sulphonylurea alone.

A study on lymphocyte subpopulation in diabetic mothers at delivery and in their newborn.

Despite the importance of immunological aspects in pregnancy, until now few studies have been reported on the cellular immune modifications of diabetic pregnancy and on the newborn of diabetic mothers. Therefore, we thought it of interest to evaluate cell immunity in diabetic pregnant women and in their newborn children. Fourteen pregnant women with Type 1 diabetes (T1DM), mean age (+/-SD) 30-4 yr, mean disease duration (+/-SD) 12+/-5 yr, 15 with gestational diabetes mellitus (GDM) (mean age 33+/-6 yr), and 21 healthy pregnant women (mean age 29+/-4 yr) were studied and their metabolic and immunological parameters were evaluated. Fifty newborn babies were examined for immunological evaluation. Mean fasting plasma glucose and HbA1c values were higher in T1DM and GDM patients than in controls. Total lymphocyte subsets were higher in T1DM and GDM patients, although there were no significant differences between the percentual values. In children of T1DM and GDM mothers absolute lymphocyte values were increased, whereas the natural killer (NK) subset had decreased values in both absolute and percentual terms. Our work shows that, with respect to healthy controls, both GDM and T1DM mothers have a significant increase in total lymphocytes, and newborns have a reduced number of NK lymphocytes. Lower numbers of NK lymphocytes are probably related to altered production of lymphokines during foetal life and may also represent a real immune deficit in monitoring against viral infections.

Myocardial dysfunction and adrenergic cardiac innervation in patients with insulin-dependent diabetes mellitus.

BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) is associated with an increased incidence of heart failure due to several factors, and in some cases a specific cardiomyopathy has been suggested. OBJECTIVES: This study sought to assess the mechanisms of exercise-induced left ventricular (LV) dysfunction in asymptomatic patients with IDDM in the absence of hypertensive or coronary artery disease. METHODS: Fourteen consecutive patients with IDDM were enrolled (10 men, 4 women; mean [+/- SD] age 28.5 +/- 6 years); 10 healthy subjects matched for gender (7 men, 3 women) and age (28.5 +/- 3 years) constituted the control group. LV volume, LV ejection fraction (LVEF) and end-systolic wall stress were calculated by two-dimensional echocardiography at rest and during isometric exercise. LV contractile reserve was assessed by post-extrasystolic potentiation (PESP) obtained by transesophageal cardiac electrical stimulation and dobutamine infusion. Myocardial iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to assess adrenergic cardiac innervation. RESULTS: Diabetic patients were classified into group A (n = 7), with an abnormal LVEF response to handgrip (42 +/- 7%), and group B (n = 7), with a normal response (72 +/- 8%). Baseline LVEF was normal in both group A and B patients (60 +/- 6% vs. 61 +/- 7%, p = NS). In group A patients, the LV circumferential wall stress-LVEF relation showed an impairment in LVEF disproportionate to the level of LV afterload. No significant changes in LVEF occurred during dobutamine (60 +/- 6% vs. 64 +/- 10%, p = NS), whereas PESP significantly increased LVEF (60 +/- 6% vs. 74 +/- 6%, p < 0.001); PESP at peak handgrip normalized the abnormal LVEF (42 +/- 7% vs. 72 +/- 5%, p < 0.001); and MIBG uptake normalized for body weight or for LV mass was lower than that in normal subjects (1.69 +/- 0.30 vs. 2.98 +/- 0.82 cpm/MBq per g, p = 0.01) and group B diabetic patients (vs. 2.79 +/- 0.94 cpm/MBq per g, p = 0.01). Finally, a strong linear correlation between LVEF at peak handgrip and myocardial MIBG uptake normalized for LV mass was demonstrated in the study patients. CONCLUSIONS: Despite normal contractile reserve, a defective blunted recruitment of myocardial contractility plays an important role in determining exercise LV dysfunction in the early phase of diabetic cardiomyopathy. This abnormal response to exercise is strongly related to an impairment of cardiac sympathetic innervation.

Hyperosmolar nonketotic coma at the onset of type I diabetes in a child.

A 12 yr-old child without any past medical history of diseases was admitted to hospital for sopor and polyuria. At admission he was markedly dehydrated. Blood glucose was 72 mmol/l, sodium 154 mmol/l, osmolarity 381 mOsm/Kg, urinary ketons were negative. He was rehydrated with hypotonic saline and treated with insulin. The osmolality and sodium initially increased to 176 mmol/l and 408 mOsm/Kg respectively and progressively decreased to normal levels. Serum transaminases increased to GOT 336 and GPT 209 U/l in the first days of treatment and normalized after 15 days. The anti-islet antibodies were positive. The non ketotic hyperosmolar coma and Type I diabetes is rare in children but this possibility must be kept in mind especially when some familial or psychological problems are present as in our case.

A study on lymphocyte subpopulations in diabetic pregnant women and their newborn.

We studied the lymphocyte subpopulations in 14 pregnant women with type 1 insulin-dependent diabetes mellitus (IDDM), mean age (+/- SD) 30 +/- 4 years, mean disease duration 12 +/- 5 years, in 14 with gestational diabetes mellitus (GDM) (mean age 33 +/- 6 years) and 21 matched healthy pregnant controls (C), when the subjects delivered, and in their newborn. The GDM and IDDM mothers show a significant increase (p < 0.05) of lymphocytes in comparison with C (GDM 1.83 +/- 0.5 x 10(9)/l, IDDM 1.6 +/- 0.68 x 10(9)/l, C 1.06 +/- 0.45 x 10(9)/l lymphocytes), which has repercussion on lymphocyte subpopulations absolute values. The newborn of GDM mothers have an increase of lymphocytes T-activated (0.6 +/- 0.3 vs 0.3 +/- 0.2%; p < 0.05) and a reduction of NK lymphocytes than C (8.9 +/- 9 vs 15.5 +/- 7.6%; p < 0.05). The newborn of IDDM mothers show a significant reduction of NK lymphocytes than C (10 +/- 6 vs 15.5 +/- 7.6%; p < 0.05). So in newborn of diabetic mothers there is a deficit of natural immunity at birth which has to be evaluated by follow-up study.

[Home care for the diabetic within the limits of project--object: pilot project integrated into the health education of the diabetic. Veneto Region]. / L'assistenza domiciliare al diabetico nell'ambito del progetto-obiettivo: progetto pilota integrato per la tutela della salute del diabetico, Regione Veneto.

Twenty one district-nurses working in 13 districts were handed a questionnaire (one questionnaire for each patient), to collect data on nursing interventions and main problems of the 382 diabetic patients cared for. The diabetic patients are a very demanding population with a mean age of 78 years; 314 (82%) have a comorbidity, 272 (71%) severe limits on their physical functioning and 233 (61%) the diabetic foot; 183 patients (47%) are not capable of taking autonomous decisions. The nursing interventions for these patients are both technical (drawing blood samples, diagnostic exams) and educational on how to manage and monitor self-administration of insulin (31 patients, 10%), on self monitoring techniques (116 patients, 30%), on alimentation in general and change in food habits (289 patients, 94.1%). The role of the nurse in promoting patients' independence and in preventing complications is highlighted.

A study on the hyperinsulinism of late pregnancy.

Much research has demonstrated that in late pregnancy glucose administration causes a marked increase of peripheral insulin levels. To ascertain whether this particular increase is due to increased insulin secretion and/or to reduced hepatic insulin removal, we measured blood glucose, plasma C-peptide and plasma insulin during OGTT in 7 nonpregnant women and in 20 nondiabetic women at third trimester of gestation and 60-90 days after delivery. The C-peptide/insulin molar ratio was calculated for all subjects. Data obtained showed that both plasma insulin and C-peptide response to oral glucose is considerably higher in women at third trimester of pregnancy as compared with that observed in the same subjects after delivery and in nonpregnant women. The basal (overnight fasting) C-peptide/insulin molar ratio did not differ significantly between pregnant and nonpregnant women. After the oral glucose load the molar ratio was sharply reduced in all groups of subjects, but the overall decrease in the pregnant women in the three hours following oral glucose was considerably greater than in postpartum and in nonpregnant women. The increased plasma C-peptide response clearly indicates that in pregnancy oral glucose-induced hyperinsulinism is caused by increased insulin release from pancreatic B-cells. Moreover, the marked overall decrease of the C-peptide/insulin molar ratio suggests, even if it does not definitely prove, that hyperinsulinism after glucose in late pregnancy may be a consequence not only of increased insulin secretion, but also of decreased hepatic extraction of insulin.

Metabolic effects of physical training in subjects with oral glucose intolerance.

A group of normal weight subjects with oral glucose intolerance was studied for 4 months before, during, and after a physical training program (8 km/day/run). There were no significant differences in weight, basal blood glucose, lactate, and total cholesterol during and after training as compared with before training. Serum triglycerides significantly (P less than 0.05) decreased during the training period, and cholesterol-HDL significantly (P less than 0.01) increased during and after the physical program. Our data show that in previously inactive subjects with oral glucose intolerance physical training improves serum lipid patterns and thereby reduces atherosclerotic risk.

Metabolic and endocrine responses to a standard mixed meal. A physiologic study.

In order to study endocrine and metabolic responses to normal food ingestion, 8 'healthy' subjects received a standard mixed meal which reflected the composition of Western diet (CHO 47%, protein 23%, fat 26%, alcohol 4%), in 20 min. Before and after the meal, in each subject glucose, lactate, FFA, insulin, C-peptide, glucagon and HGH were determined. The results showed that glycemic and insulinemic responses were not very different from those observed after the classical oral glucose tolerance test. Plasma FFA and blood lactate decreased progressively after the meal. Plasma glucagon and HGH showed opposite changes: pancreatic glucagon rose and HGH slightly declined after composite food ingestion.

The effect of propranolol on hypoglycaemia. Observations in five insulinoma patients.

Five hypoglycaemic hyperinsulinaemic patients (three with proven benign insulinoma, one with proven metastasizing insulinoma, one with probable insulinoma not found at surgery) were treated with propranolol for a variable time ranging from two weeks to one year. Three patients showed favourable clinical results and a significant increase of the mean basal blood glucose level was found while two patients showed no improvement of the frequency of neuroglycopenic episodes and no significant increase of their mean blood glucose level. No patient showed a significant decrease in mean basal IRI concentration. A decrease of insulinaemic responses was observed during oral and intravenous glucose tolerance tests, a prolonged fast, and tolbutamide and glucagon tests performed in some patients. The results suggest that propranolol may induce in certain patients an improvement of basal clinical status through not understood effects (probably hepatic), which leave the peripheral concentrations of insulin unchanged, whereas inhibition of insulin secretion may represent the main way by which the improvement of metabolic situation during physiological or pharmacological stimulation may have been achieved.

Effect of chlorpromazine on blood glucose and plasma insulin in man.

In three groups of normal subjects and in one group of patients with latent diabetes mellitus a study has been made of the effects of chlorpromazine (CPZ) on blood glucose and plasma insulin. CPZ 75 mg/day for 7 days did not alter the plasma insulin response after oral glucose; nor did CPZ 50 mg/day for 7 days affect the glucose assimilation rate or insulin response to glucose injection. Infusion of CPZ 50 mg in 60 min slightly increased the basal blood glucose level but had no significant effect on basal plasma insulin. The insulin/glucose ratio after the end of the infusion was significantly higher than during the period of infusion of the drug. In latent diabetic patients CPZ infusion significantly diminished the insulin/glucose ratio during an intravenous glucose tolerance test. These results suggest that, whereas prolonged treatment with low doses of CPZ did not modify glucose tolerance and glucose-stimulated pancreatic response, higher acute doses of the drug may induce hyperglycaemia and can inhibit insulin secretion both in normal man and in patients with latent diabetes mellitus.

Hypoglycaemia induced by adrenal gland neoplasia (Anderson's syndrome) : report of a case.

A patient with hypoglycaemia associated with an adrenal neoplasia (Anderson's syndrome) is reported. Endocrinological investigation showed increased secretion of cortisol and catecholamines as well as an increased urinary steroid excretion along with profound inhibition of both basal and stimulated insulin secretion. During IVGTT, Conard's coefficient was reduced. The hyperglycemic response to glucagon injection was blunted, suggesting that liver glycogen stores were decreased or unavailable.

Medical treatment of endogenous organic hyperinsulinism.

There are several situations in which medical therapy of hyperinsulinism induced by islet cell tumors or hyperplasia is necessary and at present we have at our disposal several drugs which are capable of reducing endogenous hyperinsulinism. They are: -Streptozotocin, which represents today the most useful therapeutic agent for beta cell carcinoma therapy; -Diazoxide, which represents the drug of first choice for the treatment of most hypoglycemic syndromes caused by islet cell adenoma or hyperplasia; -Propranolol, Chlorpromazine, Diphenylhydantoin, which may be regarded as a useful alternative to diazoxide, although they are capable of giving rather inconstant results. These drugs may today effectively substitute for corticosteroids and glucagon in the medical treatment of almost every chronic hyperinsulinemic hypoglycemic syndrome, including malignant beta cell carcinoma.