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Biomedical subjects

A Tiengo

Publications and source records attributed to A Tiengo.

At least 19 recordsLinked to original sources

A long-period, violently variable X-ray source in a young supernova remnant.

Observations with the Newton X-ray Multimirror Mission satellite show a strong periodic modulation at 6.67 +/- 0.03 hours of the x-ray source at the center of the 2000-year-old supernova remnant RCW 103. No fast pulsations are visible. If genetically tied to the supernova remnant, the source could either be an x-ray binary, composed of a compact object and a low-mass star in an eccentric orbit, or an isolated neutron star. In the latter case, the combination of its age and period would indicate that it is a peculiar magnetar, dramatically slowed down, possibly by a supernova debris disc. Both scenarios require nonstandard assumptions about the formation and evolution of compact objects in supernova explosions.

Journal Article↗

Educating diabetic patients about insulin use: changes over time in certainty and correctness of knowledge.

AIM: Diabetic patients should understand their disease correctly and be sure of what they know, but certainty is rarely considered by educators. Furthermore little is known about how certainty changes with time after an educational intervention. To clarify this, in 38 patients with type 1 diabetes (0.3-36 years duration) we analysed the effect of a course on insulin use by administering a questionnaire before the course, after the course and 1 and 3 years later. METHODS: Answers, accompanied by a subjective estimate of the degree of certainty, were assigned to mastered knowledge (certainty>or=90%, correctness>or=90%), hazardous knowledge (certainty>or=90%, correctness or=90%) and residual knowledge (total-[mastered+hazardous+uncertain]). Answers were then counted and changes in distribution among areas were analysed by the chi2 test. We also followed the fate of wrong answers. RESULTS: The course increased mastered knowledge, while other types of knowledge decreased. With time mastered knowledge decreased, patients losing both correctness and certainty. The loss affected declarative knowledge, based purely on theory, more than procedural knowledge, which concerns the way things are done. Wrong answers, mostly given with high degree of certainty, were heterogeneous since some became correct after the course, some remained wrong, some became wrong after the course, some became mistaken after having been corrected earlier. CONCLUSIONS: The analysis of certainty helps in evaluating patient's knowledge; programmes tending to improve procedural knowledge are more likely to have long lasting effects; wrong answers need to be considered on a individual basis.

Diabetes Mellitus, Type 1↗

Lower within-subject variability of fasting blood glucose and reduced weight gain with insulin detemir compared to NPH insulin in patients with type 2 diabetes.

AIM: The aim of this study was to compare the efficacy and safety of a basal-bolus insulin regimen comprising either insulin detemir or neural protamine hagedorn (NPH) insulin in combination with mealtime insulin aspart in patients with type 2 diabetes. METHODS: This was a 26-week, multinational, open-label, parallel group trial with 505 patients with type 2 diabetes (mean age, 60.4 +/- 8.6 years; mean BMI, 30.4 +/- 5.3 kg/m(2); mean HbA(1c), 7.9 +/- 1.3%). Patients, randomized 2:1 to insulin detemir or NPH insulin, received basal insulin either once or twice daily according to their pretrial insulin treatment and insulin aspart at mealtimes. RESULTS: After 26 weeks of treatment, significant reductions in HbA(1c) were observed for insulin detemir (0.2%-points, p = 0.004) and NPH insulin (0.4%-points; p = 0.0001); HbA(1c) levels were comparable at study end (insulin detemir, 7.6%; NPH insulin, 7.5%). The number of basal insulin injections administered per day had no effect on HbA(1c) levels (p = 0.50). Nine-point self-measured blood glucose (SMBG) profiles were similar for the two treatment groups (p = 0.58), as were reductions in fasting plasma glucose (FPG) (insulin detemir, 0.5 mmol/l; NPH insulin, 0.6 mmol/l). At study end, FPG concentrations were similar for the two treatment groups (p = 0.66). By contrast, within-subject day-to-day variation in fasting SMBG was significantly lower with insulin detemir (p = 0.021). Moreover, patients receiving insulin detemir gained significantly less body weight than those who were administered NPH insulin (1.0 and 1.8 kg, respectively, p = 0.017). The frequency of adverse events and the risk of hypoglycaemia were comparable for the two treatment groups. CONCLUSIONS: Patients with type 2 diabetes, treated for 26 weeks with insulin detemir plus insulin aspart at mealtimes, experienced comparable glycaemic control but significantly lower within-subject variability and less weight gain compared to patients treated with NPH insulin and insulin aspart. Insulin detemir was well tolerated and had a similar safety profile to NPH insulin.

Aged↗

Role of anti-granulocyte Fab' fragment antibody scintigraphy (LeukoScan) in evaluating bone infection: acquisition protocol, interpretation criteria and clinical results.

Scintigraphy using anti-granulocyte Fab' fragment (LeukoScan) was performed in a series of 220 consecutive patients with suspected bone infection referred to our centre between September 1999 and June 2002. Two protocols were compared for interpreting scans: (1) evaluation of early 4 h imaging alone (protocol A), and (2) evaluation both of early and delayed 24 h imaging (protocol B). Protocol A and protocol B showed equal values of sensitivity (91.9% in patients with diabetic foot and 84.2% in patients with joint prosthesis/peripheral bone implants). Conversely, specificity was higher adopting protocol B than protocol A: 87.5% vs 75.0% in patients with diabetic foot, and 85.7% vs 76.2% in patients with joint prosthesis/peripheral bone implants, respectively. In particular, an improvement in specificity using protocol B was found in those patients with infection and with only a mild LeukoScan uptake in the early 4 h imaging: in these patients an increasing uptake intensity pattern observed in the delayed 24 h imaging was indicative of infection while a decreasing pattern suggested a negative result. Instead, the evidence of a high uptake intensity in the early LeukoScan imaging was a strong indicator of infection and delayed imaging in these cases did not further improve specificity. In conclusion, in our experience, LeukoScan showed high sensitivity in diagnosing bone infection in patients with diabetic foot and joint prosthesis or other peripheral bone implants. Moreover, in patients with an early high LeukoScan uptake intensity further delayed images appears unnecessary for the purpose of diagnosing infection. In contrast in patients with an early mild LeukoScan uptake intensity only, delayed imaging appears to be recommendable for improving specificity.

Adult↗

Effect of sodium intake on blood pressure and albuminuria in Type 2 diabetic patients: the role of insulin resistance.

AIMS/HYPOTHESIS: This study was done to measure the effect of Na+ intake on blood pressure and albuminuria, in relation with insulin sensitivity and kidney haemodynamics, in Type 2 diabetic patients with and without microalbuminuria. METHODS: Type 2 diabetic patients, 20 with microalbuminuria, 21 without, spent two consecutive 7-day periods, one on a high (250 mmol), the other on a low-Na+ (20 mmol) diet. Body weight, 24-h blood pressure and albuminuria were measured at the end of each period. At the end of high-Na+ diet insulin sensitivity (euglycaemic insulin clamp; 2 mU.kg(-1).min(-1)) and kidney haemodynamics were measured in nine patients from each group. RESULTS: Switching from low to high-Na+ diet resulted in an increase in blood pressure (7.4+/-4.7 mmHg; p<0.001), body weight (1.9+/-0.4 kg; p<0.05) and albuminuria [from 80 (31-183) microg/min to 101 (27-965) microg/min; p<0.01) in patients with microalbuminuria. No changes occurred in patients without microalbuminuria. Patients with microalbuminuria also had greater intraglomerular pressure (44+/-1 mmHg vs 36+/-1; p<0.001), calculated from glomerular filtration rate, renal plasma flow, plasma protein concentration and the relationship between pressure and natriuresis. In these patients insulin sensitivity was lower (5.16+/-49 vs 7.36+/-0.63 mg.kg(-1).min(-1); p=0.007). Urinary albumin excretion (r=0.40; p=0.009) and insulin sensitivity (r=-0.59; p=0.01) were correlated with intraglomerular pressure. CONCLUSION/INTERPRETATION: High salt intake increases blood pressure and albuminuria in Type 2 diabetic patients with microalbuminuria. These responses are associated with insulin resistance and increased glomerular pressure. Insulin resistance could contribute to greater salt sensitivity, increased glomerular pressure and albuminuria.

Albuminuria↗

In situ protein Kinase C activity is increased in cultured fibroblasts from Type 1 diabetic patients with nephropathy.

AIMS/HYPOTHESIS: To verify whether individual susceptibility to diabetic nephropathy resides in an intrinsic difference in Protein Kinase C (PKC) activity. METHODS: We compared the effect of different glucose concentrations on PKC activity, PKC isoform expression and diacylglycerol (DAG) content in cultured fibroblasts from 14 Type 1 diabetic patients who developed nephropathy with those in cells from 14 patients without nephropathy. We recruited 14 normal subjects as control patients. Forearm skin fibroblasts were cultured in either normal (5 mmol/l) or high (20 mmol/l) glucose concentrations. RESULTS: In normal glucose, in situ PKC activity was higher in Type 1 patients with nephropathy (10.1+/-1.4 pmol/min/mg protein; p<0.01) than in those without (6.8+/-0.8) and the normal control subjects (6.3+/-0.5). This difference was due to increased concentrations of PKCalpha isoform in the membrane fraction of fibroblasts from patients with nephropathy. DAG content was also higher in cells from Type 1 patients with nephropathy. Incubation in high glucose concentration caused a further increase in PKC activity and DAG content in quiescent fibroblasts from patients with diabetic nephropathy, with no significant changes in cells from diabetic patients without nephropathy and normal control subjects. CONCLUSION/INTERPRETATION: Differences in PKC activation could contribute to the individual susceptibility to renal damage in Type 1 diabetic patients.

Adult↗

Moderate alcohol consumption, glucose metabolism and lipolysis: the effect on adiponectin and tumor necrosis factor alpha.

Moderate alcohol consumption has a cardioprotective effect on coronary artery disease. Among the beneficial effects of alcohol, a suppression of the plasma free fatty acid (FFA) concentration has been shown but the mechanism which accounts for this action is not clear. We assessed whether moderate alcohol intake affects plasma adiponectin levels and tumor necrosis factor (TNF)-alpha, two regulators of lipolysis. Oral glucose tolerance tests were performed twice on 22 volunteers: "the alcohol study" and "control study". In the former, red wine was sipped to maintain steady state alcohol concentration. Samples for plasma glucose, insulin, FFA, adiponectin, and TNF-alpha concentrations were obtained. In the latter, tap water was sipped. Insulin action has been assessed by the Oral Glucose Insulin Sensitivity (OGIS) Model. The mean blood alcohol concentration was 5+/-2 mg/dl. No differences were observed between the two studies in the OGIS (406+/-19 ml x min(-1) x m(-2) with alcohol and 402+/-20 without, respectively). Baseline FFA levels were lower in the alcohol study; however, post-glucose inhibition was comparable. No differences in the TNF-alpha and adiponectin responses were observed. A significant correlation was observed between the OGIS index and the fasting adiponectin level (r=0.589, p<0.0001). Moderate red wine intake improves post-glucose FFA profiles but does not modify the plasma concentrations of both TNF-alpha and of adiponectin concentrations: the latter is significantly and positively associated to the insulin action. Further studies are needed to clarify the antilipolytic effect of moderate alcohol intake.

Adiponectin↗

Visceral obesity is characterized by impaired nitric oxide-independent vasodilation.

BACKGROUND: Endothelial dysfunction has been described in obesity. This study examines the impact of visceral obesity on nitric oxide-independent relaxation in the human forearm. METHODS AND RESULTS: In ten viscerally obese and ten matched controls forearm blood flow (FBF) was measured by venous occlusion plethysmography during intrabrachial infusion of: (1) sodium nitroprusside; (2) bradykinin, before and after inhibition of vasoactive prostaglandins and nitric oxide; (3) potassium; (4) ouabain (Na(+)/K(+)ATPase inhibitor) alone or (5) in combination with BaCl(2)(K(IR)inhibitor). Baseline FBF and endothelium-independent vasodilatation were similar in the two groups. In obese patients, bradykinin-induced increase of FBF was significantly less than in controls (P<0.01). Irrespective of prostaglandins and nitric oxide inhibition, bradykinin response was lower in the viscerally obese. Intrabrachial potassium determined a significantly blunted response (P<0.05). Ouabain caused a similar, moderate decrease in basal FBF in the two groups; the coinfusion of BaCl(2)caused a more intense decline in FBF which was significantly relevant in obese (-24+/-5%, P<0.01). CONCLUSIONS: In obese patients there is a blunted nitric oxide-independent relaxation determined by a decreased response of inwardly rectifying potassium channels.

Adult↗

Continuous subcutaneous insulin infusion (CSII) in the Veneto region: efficacy, acceptability and quality of life.

AIM: To study the effect of continuous subcutaneous insulin infusion (CSII) on metabolic control and well-being in patients with Type 1 diabetes. METHODS: Efficacy, safety and interference with everyday life associated with CSII were studied retrospectively in 138 diabetic patients from the Veneto region treated for 7.4 +/- 0.4 years. RESULTS: Glycosylated haemoglobin decreased during the first year of CSII from 9.3 +/- 0.2% to 7.9 +/- 0.1% (P < 0.0001), and then remained unchanged. Serious hypoglycaemia decreased from 0.31 +/- 0.07/year to 0.09 +/- 0.02/year (P < 0.003), as did ketoacidosis (from 0.41 +/- 0.12/year to 0.11 +/- 0.03/year, P < 0.013). During the first year of therapy daily insulin requirement decreased from 49 +/- 1 to 42 +/- 2 U/day (P < 0.0001) and did not change thereafter. The number of out-patient consultations and hospital admissions per year also decreased significantly. CSII was associated with a progressive increase of body weight (P < 0.05) and with 0.2 +/- 0.04 infections/patient per year at the infusion site. Infection was rated as mild in 72%, moderate in 18%, severe in 10%. Patients reported that CSII improved metabolic control (71%), sense of well-being (41%), and allowed more freedom (40%). Quality of life, assessed using the DQOL, after 7 years of CSII was rated as good by patients (score of 73.0 +/- 1.8 on a scale from 0 to 100). CONCLUSIONS: This retrospective analysis suggests that CSII improves metabolic control in Type 1 diabetic patients, reduces hypoglycaemic and ketoacidotic events, is well accepted, allows a good quality of life and decreases out-patient consultations and hospital admissions.

Administration, Cutaneous↗

Diabetic ketosis activates lymphomonocyte-inducible nitric oxide synthase.

AIMS: Inappropriate production of nitric oxide (NO) may be responsible for the haemodynamic disturbances of diabetic ketoacidosis. We investigated whether this metabolic condition is associated with increased plasma nitrate (the stable oxidation product of NO) levels and NO synthase gene expression in lymphomonocytes. RESEARCH DESIGN AND METHODS: Plasma nitrate concentrations, lymphomonocyte-inducible nitric oxide synthase (iNOS) gene expression, tumour necrosis factor-alpha (TNF-alpha) and soluble thrombomodulin were measured in 11 Type 1 diabetic patients at baseline, during mild ketosis and after euglycaemia was re-established. RESULTS: During diabetic ketosis plasma nitrate concentrations were higher (18 (16-21) vs. 9 (7-11) micro mol/l; (95% lower-upper confidence interval) P < 0.05) than at baseline. At baseline lymphomonocyte iNOS mRNA expression and iNOS protein levels were undetectable, but in ketosis both were increased (both at P < 0.0001). After recovery from ketosis, NO3 concentration, iNOS mRNA, and iNOS expression (270 +/- 36%, mean +/- sd) decreased but not significantly. No significant changes were observed in either TNF-alpha or soluble thrombomodulin levels between the three conditions. CONCLUSIONS: Diabetic ketosis is associated with increased nitrate levels and the activation of iNOS expression in circulating lymphomonocytes, but it does not affect either the proinflammatory cytokine TNF-alpha or a marker of endothelial dysfunction such as thrombomodulin. Our data support the hypothesis that, during diabetic ketosis, alterations in NO homeostasis are present in circulating lymphomonocytes.

Adult↗

Glycaemic control and microvascular complications in a large cohort of Italian Type 1 diabetic out-patients.

The purpose of this cross-sectional study was to evaluate the degree of metabolic control, the prevalence of microvascular complications (nephropathy, retinopathy, and peripheral neuropathy) and their association with risk factors for cardiovascular diseases in all adult Type 1 diabetic out-patients attending 2 Diabetes Clinics of Northern Italy over 12 months. A total of 458 patients (mean age 37 +/- 12 yr, duration of diabetes 15.3 +/- 10.6 yr, BMI 23.2 +/- 3.1 kg/m2) were studied. Clinical characteristics and microvascular complications were evaluated. The proportion of patients with a good glycaemic control (HbA1c < 7%) was 14.7%. Nephropathy was observed in 24.4%, retinopathy in 41%, peripheral neuropathy in 23.7%. The prevalence of hypertension was 30.3%. Microvascular complications were associated with age, duration of diabetes, systolic blood pressure, creatinine, triglycerides and cholesterol plasma levels. Mean HbA1c was 8.5 +/- 1.6. Patients with HbA1c levels < 7% presented a lower prevalence of complications and lower levels of cholesterol, triglycerides, systolic blood pressure than patients with HbA1c > 9%. Our study indicates that an acceptable metabolic control is achieved in a too low proportion of Type 1 diabetic patients, even under multiple insulin injections. The association of poor metabolic control and microalbuminuria identifies a group of patients at higher risk of diabetic complications.

Adult↗

Serum protein profiles of patients with pancreatic cancer and chronic pancreatitis: searching for a diagnostic protein pattern.

In this study, 13 sera from patients with pancreatic cancer, 9 from chronic pancreatitis and 10 from healthy subjects were analyzed by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The MALDI mass spectra revealed the presence of several low molecular weight peptides, among which some were detected only in the sera from both pathological conditions. On the other hand many peptides were observed only in control sera, and were absent in the sera from the two diseases. Therefore, MALDI analysis of the low molecular weight fraction (<10 000 Da) of sera from patients with pancreatic diseases enabled us to identify the presence of some disease-related signals and also some signals characteristic of normal subjects.

Aged↗

Combination of continuous subcutaneous infusion of insulin and octreotide in Type 1 diabetic patients.

The effect of 7 day continuous subcutaneous infusion of octreotide (200 microg day(-1)) was evaluated in seven insulin-pump treated Type 1 diabetic patients (age 43+/-1.5 year; BMI 25.1+/-0.7 kg m(-2); HbA(1c) 7.4+/-0.3%). A 24-h metabolic and hormonal profile, and a euglycaemic hyperinsulinaemic clamp (0.25, 0.5, 1.0 mg kg(-1) min(-1)), with [3H]glucose infusion and indirect calorimetry, were performed before and after a 7-day octreotide infusion. Mean 24-h plasma glucose was similar before and after octreotide (9.7+/-0.8 vs. 9.1+/-1.0 mmol l(-1)) but insulin requirement dropped by 45% (49+/-4 vs. 27+/-2 U day(-1); P<0.01). Both 24-h plasma hGH and glucagon were suppressed by octreotide (1.85+/-0.35 vs. 0.52+/-0.04 microg l(-1), and 117+/-23 vs. 102+/-14 ng l(-1), respectively). Glucose utilisation increased after octreotide (insulin 0.5 mU kg(-1) min(-1) clamp 3.09+/-0.23 vs. 4.19+/-0.19 mg kg(-1) min(-1); 1 mU kg(-1) min(-1) clamp 5.64+/-0.61 vs. 7.93+/-0.57 mg kg(-1) min(-1); both P<0.05) and endogenous glucose production was similarly suppressed. Glucose oxidation was not affected by octreotide, while the improvement in glucose storage (insulin 1.0 mU kg(-1) min(-1) clamp 3.89+/-0.60 vs. 5.64+/-0.67 mg kg(-1) min(-1), P<0.05) entirely accounted for the increase in glucose disposal. Endogenous glucose production was more effectively suppressed at the two lower insulin infusion rates (P>0.05). Energy expenditure declined after octreotide. Continuous subcutaneous octreotide infusion suppresses counterregulatory hormones, increases insulin-mediated glucose metabolism by enhancing glucose storage, and reduces energy expenditure. These results support a role for counterregulatory hormones in the genesis of insulin resistance and the catabolic state of Type 1 diabetes.

Adult↗

Gemfibrozil improves insulin sensitivity and flow-mediated vasodilatation in type 2 diabetic patients.

BACKGROUND: Endothelial dysfunction is an early feature of atherosclerosis. The relationship between insulin action and hypertriglyceridaemia on endothelial function is still debated. MATERIALS AND METHODS: This study was designed to determine the effect of a 3 month treatment with Gemfibrozil (GF) on flow-mediated vasodilatation and insulin sensitivity. Ten type 2 diabetic patients were randomised in crossover, double blind fashion, either to GF, 600 mg b.i.d. or placebo, for 12 weeks. Lipid profile, low-density lipoprotein (LDL) distribution and flotation properties, insulin action and flow-mediated vasodilatation (FMD) by brachial artery ultrasound, were assessed. RESULTS: GF decreased serum triglyceride (TG) concentration with an absolute difference of 1.79 +/- 1.28 mmol L-1 (P < 0.0016) between active treatment and placebo, and significantly increased serum high-density lipoprotein (HDL) cholesterol (P = 0.0233). No differences were observed in total, intermediate-density lipoproteins (IDL), LDL cholesterol concentration and LDL peak buoyancy between treatments. GF also improved SI, an index of insulin action (P = 0.005). The FMD was 7 +/- 3% in the baseline condition, 7 +/- 2% during placebo and 14 +/- 3% after GF (P < 0.006). CONCLUSIONS: GF treatment improves both insulin action and flow-mediated vasodilatation in type 2 diabetic patients. The reduction of TG concentration allows the simultaneous correction of two important components of the metabolic syndrome.

Aged↗

Insulin infusion normalizes fasting and post-prandial albumin and fibrinogen synthesis in Type 1 diabetes mellitus.

AIMS: The effect of metabolic control on hepatic synthesis of plasma proteins in Type 1 diabetes mellitus (T1DM), in the post-absorptive and post-prandial state, is not known. METHODS: We measured fractional synthetic rates (FSR) of albumin and fibrinogen in six insulin-infused T1DM patients and in five to nine control subjects, before and for approx. 4 h after a mixed liquid meal. Phenylalanine tracer precursor/product relationships and steady-state conditions were used. In the post-absorptive state, patients were studied in near euglycaemic conditions after an overnight intravenous insulin infusion. During the meal (approx. 11 kcal/kg), the insulin infusion rate was increased to maintain plasma glucose concentrations below approx. 10 mmol/l. RESULTS: Post-absorptive FSR of albumin (5.7 +/- 0.6%/day) and fibrinogen (11.3 +/- 0.6%/day) in T1DM were similar to control values (6.4 +/- 0.9 and 13.1 +/- 1.1, respectively). After the meal, albumin FSR increased (P = 0.0032 by anova) in both groups (T1DM, to 14.4 +/- 2.7%/day; controls, to 18.2 +/- 3.7%/day). Fibrinogen FSR also increased (P = 0.0048 by anova) in both the T1DM (to 18.2 +/- 2.6) and the control subjects (to 27.3 +/- 6.2). There was no difference between T1DM and control subjects in the post-prandial FSR of both proteins. CONCLUSIONS: Albumin and fibrinogen FSR in T1DM can be maintained within near-normal ranges by insulin infusion under post-absorptive and post-prandial conditions.

Adult↗

Teaching and training programme on carbohydrate counting in Type 1 diabetic patients.

Carbohydrates (CHO) are a major determinant of post-prandial blood glucose in the diet of people with Type 1 diabetes mellitus, but patients frequently fail to evaluate CHO food content. Poor education is thought to contribute heavily to this failure. Our aim was to plan and evaluate a simple educational program to improve dietary knowledge and teach how to count CHO in Type 1 diabetic subjects. Forty-eight patients (age 27+/-1 yr, diabetes duration 11+/-1 yr, HbA1c 9%) attended 4 interactive meetings held at monthly intervals. The targets of the course were: 1) to identify sources of CHO, fats and proteins; 2) to count CHO and to split them among meals; 3) to assume CHO-rich foods without changing daily calorie or carbohydrate intake; 4) to modify the diet so as to correct hypoglycaemic events. To evaluate the effect of the course, patients completed a 7-day food record and answered a questionnaire covering the targets of the course at baseline, at the end of the course and 7 months later. After the course dietary knowledge improved significantly. The number of patients who weighed foods, estimated CHO food content and correctly distributed CHO among meals also increased. After the course patients reacted better when faced with hypoglycaemia. The knowledge acquired persisted 7 months after the end of the course. Therefore, we conclude that a simple teaching program can improve diet knowledge in Type 1 diabetics and establish a sustained habit of counting CHO.

Adolescent↗

Left ventricular mass in type 2 diabetes mellitus. A study employing a simple ECG index: the Cornell voltage.

Both type 2 diabetes mellitus (DM2) and left ventricular hypertrophy are associated with an increased risk of cardiovascular diseases (CVD). A strong association between hyperinsulinemia, which is the hallmark of DM2 and of insulin resistance syndrome (a cohort of metabolic abnormalities such as DM2, dyslipidemia, hyperuricemia, obesity, hypertension, hyperfibrinogenemia), and left ventricular (LV) hypertrophy was found in several studies. We studied 140 consecutive (both normo- and hypertensive) DM2 patients to determine a possible link between metabolic features and the degree of LV mass, calculated by the ECG method of Cornell voltage. The Cornell voltage value was 12.9+/-0.5 mm in the DM2 population as a whole, and 13.6+/-0.7 vs 11.7+/-0.9 mm (p=NS) in hypertensive and normotensive DM2 subgroups, respectively. Among all the metabolic parameters taken into account, the multivariate analysis shows that the fasting plasma insulin level is the strongest independent predictor of LV mass, both in the whole population (p=0.0005) and in the normo (p=0.0460) and hypertensive DM2 (p=0.0184) subgroups.

Adult↗

Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and type I diabetic subjects.

AIMS/HYPOTHESIS: We have previously shown that lactate protects brain function during insulin-induced hypoglycaemia. An adaptation process could, however, not be excluded because the blood lactate increase preceded hypoglycaemia. METHODS: We studied seven healthy volunteers and seven patients with Type I (insulin-dependent) diabetes mellitus with a hyperinsulinaemic (1.5 mU.kg-1.min-1) stepwise hypoglycaemic clamp (4.8 to 3.6, 3.0 and 2.8 mmol/l) with and without Na-lactate infusion (30 mumol.kg-1.min-1) given after initiation of hypoglycaemic symptoms. RESULTS: The glucose threshold for epinephrine response was similar (control subjects 3.2 +/- 0.1 vs 3.2 +/- 0.1, diabetic patients = 3.5 +/- 0.1 vs 3.5 +/- 0.1 mmol/l) in both studies. The magnitude of the response was, however, blunted by lactate infusion (AUC; control subjects 65 +/- 28 vs 314 +/- 55 nmol/l/180 min, zenith = 2.6 +/- 0.5 vs 4.8 +/- 0.7 nmol/l, p < 0.05; diabetic patients = 102 +/- 14 vs 205 +/- 40 nmol/l/180 min, zenith = 1.4 +/- 0.4 vs 3.2 +/- 0.3 nmol/l, p < 0.01). The glucose threshold for symptoms was also similar (C = autonomic 3.0 +/- 0.1 vs 3.0 +/- 0.1, neuroglycopenic = 2.8 +/- 0.1 vs 2.9 +/- 0.1 mmol/l, D = autonomic 3.2 +/- 0.1 vs 3.2 +/- 0.1, neuroglycopenic 3.1 +/- 0.1 vs 3.2 +/- 0.1 mmol/l) but peak responses were significantly attenuated by lactate (score at 160 min C = 2.6 +/- 1 vs 8.8 +/- 1, and 0.4 +/- 0.4 vs 4.8 +/- 1, respectively; p = 0.02-0.01, D = 1.3 +/- 0.5 vs 6.3 +/- 1.7, and 2.3 +/- 0.6 vs 5.7 +/- 1.1 p = 0.07-0.02). Cognitive function deteriorated in both studies at similar glucose thresholds (C = 3.1 +/- 0.1 vs 3.0 +/- 0.1, D = 3.2 +/- 0.1 vs 3.3 +/- 0.2 mmol/l). Although in normal subjects a much smaller impairment was observed with lactate infusion (delta four-choice reaction time at 160 min = 22 +/- 12 vs 77 +/- 31 ms; p = 0.02), in Type I diabetic patients lactate infusion was associated with an improvement in cognitive dysfunction (0.2 +/- 0.4 vs -38 +/- 0.2 delta ms, p = 0.0001). CONCLUSION/INTERPRETATION: A blood lactate increase after the development of hypoglycaemic symptoms reduces counterregulatory and symptomatic responses to insulin-induced hypoglycaemia and favours brain function rescue both in normal and diabetic subjects. These findings confirm that lactate is an alternative substrate to glucose for cerebral metabolism under hypoglycaemic conditions.

Acclimatization↗