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Biomedical subjects

T Heise

Publications and source records attributed to T Heise.

At least 37 records · Page 2Linked to original sources

A cross-over evaluation of different methods and devices to measure blood pressure in type 1 diabetic patients with nephropathy.

BACKGROUND: In type 1 diabetic patients with nephropathy, tight blood pressure control has been shown to prevent the progression of the disease. Up until now, self-monitoring, ambulatory and office blood pressure values have not been compared in these patients. Thus, we have evaluated blood pressure values obtained in the office by a physician and at home by self-monitoring with those measured under ambulatory conditions in these patients. Additionally, for blood pressure self-monitoring, three different devices (the sphygmomanometer, upper-arm oscillometer and wrist oscillometer) were compared. METHODS: Twenty-one treated hypertensive type 1 diabetic patients [age 45+/-9 years, duration of diabetes 33+/-12 years (mean+/-SD)] with overt diabetic nephropathy participated in this study. At both baseline and the end of the study, daytime ambulatory blood pressure measurement was performed. Office blood pressure was measured at baseline. Additionally, all the patients measured their blood pressure over a 3-week period using each of the three different devices, in random order, for 1 week. RESULTS: The mean office blood pressure values (135+/-21/85+/-12mmHg) were higher than both the ambulatory (131+/-23/80+/-12, P<0.05) and self-monitoring values (130+/-14/78+/-10; P<0.05 for systolic and P<0.02 for diastolic values). The difference between the ambulatory and self-monitoring values were not statistically significant. Diastolic blood pressure values measured with the oscillometric wrist device showed a trend towards higher values when compared to those measured with the sphygmomanometer and with the oscillometric upper-arm device (P=0.065 for diastolic values). CONCLUSION: Office blood pressure measurements may over-estimate blood pressure in patients with type 1 diabetes and diabetic nephropathy. Because the oscillometric wrist device tends to over-estimate diastolic values, upper-arm devices should be preferred for blood pressure self-monitoring in these patients.

Arm↗

Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo.

OBJECTIVE: To study the pharmacodynamic properties of the subcutaneously injected long-acting insulin analog HOE901 (30 microg/ml zinc) in comparison with those of NPH insulin and placebo. RESEARCH DESIGN AND METHODS: In this single-center double-blind euglycemic glucose clamp study, 15 healthy male volunteers (aged 27 +/- 4 years, BMI 22.2 +/- 1.8 kg/m2) received single subcutaneous injections of 0.4 U/kg body wt of HOE901, NPH insulin, or placebo on 3 study days in a randomized order. The necessary glucose infusion rates (GIRs) to keep blood glucose concentrations constant at 5.0 mmol/l were determined over a 30-h period after administration. RESULTS: The injection of HOE901 did not induce the pronounced peak in metabolic activity observed with NPH insulin (GIRmax 5.3 +/- 1.1 vs. 7.7 +/- 1.3 mg x kg(-1) x min(-1)) (P < 0.05); after an initial rise, metabolic activity was rather constant over the study period. This lack of peak was confirmed by a lower glucose consumption in the first 4 h after injection (area under the curve from 0 to 4 h [AUC(0-4 h)] 1.02 +/- 0.34 vs. 1.48 +/- 0.34 g/kg) (P < 0.001) with HOE901, as compared with NPH insulin. In this single-dose study, the metabolic effect measured over a period of 30 h was lower with HOE901 than with NPH insulin (AUC(0-30 h) 7.93 +/- 1.82 vs. 9.24 +/- 1.29 g/kg) (P < 0.05). CONCLUSIONS: This study shows that the soluble long-acting insulin analog HOE901 induces a smoother metabolic effect than NPH insulin, from which a better substitution of basal insulin requirements may follow.

Adult↗

Intra-individual variability of the metabolic effect of inhaled insulin together with an absorption enhancer.

OBJECTIVE: To study the metabolic effect and the variability of the effect elicited by inhalation of 87.2 U insulin powder combined with an absorption enhancer. The metabolic effect was compared with that of 10.2 U regular insulin injected subcutaneously and of 5.5 U regular insulin given intravenously RESEARCH DESIGN AND METHODS: In this single-center open euglycemic glucose clamp study 13 healthy male volunteers received 5 insulin administrations on separate study days: once as an intravenous dose, once as a subcutaneous injection, and 3 times by inhalation, in randomized order. Glucose infusion rates (GIRs) necessary to keep blood glucose concentrations constant at 5.0 mmol/l were determined over an 8-h period after administration. RESULTS: After inhalation of the insulin powder aerosol, the onset of action was substantially more rapid than after subcutaneous insulin injection, and maximal action was reached earlier (86+/-47 vs. 182+/-53 min, P<0.0001). The maximal glucose infusion rate after inhalation of insulin was comparable to that after subcutaneous insulin injection (9.2+/-2.6 vs. 8.8+/-2.8 mg x kg(-1) x min(-1), NS). The metabolic effect in the first 2 h after inhalation was significantly greater than that after subcutaneous insulin injection (amount of glucose infused: 0.88+/-0.25 vs. 0.59+/-0.20 g x kg(-1) x 120 min(-1), P<0.0001). However, the total metabolic effect after inhalation and subcutaneous injection was comparable (2.50+/-0.76 vs. 2.56+/-0.69 g x kg(-1) x 480 min(-1), NS). The relative bioefficacy of inhaled insulin calculated in relation to the data from the subcutaneous insulin application was 12.0+/-3.5% (absolute bioefficacy 10.1+/-3.1%) but was highest in the first 2 h after application (18.5+/-3.7%; absolute bioefficacy 8.2+/-4.1%). The intraindividual variability of the metabolic response induced by insulin inhalation was 14+/-9% for the maximal glucose infusion rate, 15+/-10% for the time-to-maximal effect, and 16+/-12% for the total amount of glucose infused. CONCLUSIONS: This feasibility study shows that inhaled insulin with an absorption enhancer has a pronounced metabolic effect compared with the results of a previous study of inhaled insulin without an enhancer. The intraindividual variability of the metabolic effect was comparable with that of inhaled and subcutaneously injected insulin.

Administration, Inhalation↗

Time-action profile of the soluble, fatty acid acylated, long-acting insulin analogue NN304.

AIMS: To compare the pharmacokinetic and pharmacodynamic properties of subcutaneously injected NN304, a novel long-acting insulin analogue, to NPH-insulin during euglycaemic glucose clamps in 11 healthy volunteers. METHODS: On three study days NN304 was injected in three different doses (0.15, 0.3, 0.6 U/kg body weight), while NPH-insulin (0.3 U/kg) was injected in identical dose on two other days. RESULTS: Injection of NN304 resulted in a linear and proportional increase in total NN304 concentrations (AUC0-1440 min: 0.15 U/kg: 344+/-43, 0.3 U/kg: 666+/-82, 0.6 U/kg: 1295+/-210 nmol/l; P<0.001). Maximal concentrations (609+/-140, 1046+/-283, 2033+/-460 pmol/l; P<0.001) were reached after 4-6 h. The metabolic response (expressed as maximal glucose infusion rates (GIR)) induced by subcutaneous injection of NN304 did not show the pronounced peak seen with NPH-insulin in an identical dose: GIRmax 3.2+/-1.1 vs. 4.4+/-1.8 mg/kg/min (P<0.05 for 0.3 U/kg NN304 vs. NPH-insulin; mean of both study days with NPH-insulin, all others not significant). NN304 also showed a slower onset of action, as indicated by a significantly higher tmax (446+/-162 vs. 359+/-175 min) and lower AUC0-240min (0.5+/-0.3 vs. 0.8+/-0.4 g/kg/240min; P<0.05, respectively). The three different doses of NN304 induced a significantly different glucose consumption in the first 720 min after injection (AUC0-720 min 1.1+/-0.6, 1.9+/-0.8, 1.7+/-0.8 g/kg; P<0.05 for 0.15 U/kg), but not over the whole study period (AUC0-1440 min 1.8+/-1.1, 3.1+/-1.3, 2.8+/-1.4 g/kg). CONCLUSIONS: Injection of NN304 at different doses resulted in an increase in total NN304 concentration in a linear dose-response effect and a more even metabolic effect than NPH-insulin. However, we found no clear dose-response in its metabolic effect.

Acylation↗

Measurement of insulin sensitivity: influence of potassium supply during euglycaemic glucose clamps in healthy volunteers.

Insulin sensitivity can be quantitatively measured by the hyperinsulinaemic euglycaemic glucose clamp technique. Infusion of insulin during the clamp procedure leads to a decline of kalaemia unless potassium is supplied. We investigated whether supplementation of potassium during euglycaemic glucose clamps influences insulin sensitivity. In a randomised study the insulin sensitivity index (S(I)) was determined with two-step hyperinsulinaemic (insulin infusion rates 0.25 (step 1) and 1.0 mU kg(-1) min(-1) (step 2)) euglycaemic (5.0 mmol L(-1)) glucose clamps in 20 healthy male volunteers on two different study days. On one day blood potassium was kept constant by means of a variable i.v. potassium chloride infusion ("eukalaemic potassium clamp"), whereas on the other day the decline in blood potassium was monitored only. Without potassium supply kalaemia decreased from basal levels of 4.35 +/- 0.18 mval L(-1) to 4.25 +/- 0.17 (step 1) and further to 3.88 +/-0.14 mval L(-1) (step 2 (mean +/- SD)). Without and with potassium supply the insulin sensitivity index measured was comparable (S1 10.6 +/- 3.6 vs. 9.5 +/- 3.5 ml min(-1) m2 per microU ml(-1), n.s.; glucose infusion rates 3.6+/-1.6/12.6 +/- 2.6 (step 1/step 2) vs. 3.7 +/- 1.5/12.2 +/- 2.7 mg kg(-1) min(-1), n.s.). In conclusion, this study shows that potassium supply during hyperinsulinaemic euglycaemic glucose clamps in healthy subjects does not influence the insulin sensitivity index.

Adult↗

Lack of effects of the beta3-adrenoreceptor agonist UL-TG 307 on insulin sensitivity and insulin secretion in Type 2 diabetic patients.

The effects of a novel beta3-adrenoreceptor agonist, UL-TG 307, on insulin sensitivity and insulin secretion, lipid metabolism, and body weight were investigated. Thirteen diet treated male Type 2 diabetic patients participated in a randomized, double-blind, placebo controlled cross-over trial with two 14 day administration periods with placebo and UL-TG 307 (24 mg daily). After each administration period insulin secretion was assessed by means of an OGTT and insulin sensitivity was measured by an hyperinsulinaemic euglycaemic glucose clamp. Lipid metabolism was evaluated by measuring non-esterified fatty acid, glycerol, and triglyceride serum concentrations at the end of each administration period. Treatment with UL-TG 307 did not improve insulin sensitivity (insulin sensitivity index (S(I)): UL-TG 307 2.5 -/+ 0.6 (mean +/- SD) vs. placebo 2.2 +/- 0.8 ml/min*m2 per microU/ml) nor increased insulin secretion (area under the serum insulin profile AUC0-240/plasma glucose AUC0-240: UL-TG 307 8.8 +/- 7.4 vs. placebo 8.3 +/- 6.4 microU/ ml/mmol/l). No differences in lipid metabolism, metabolic control, and body weight were observed. We conclude that two weeks' administration of the beta3-adrenoreceptor agonist UL-TG 307 in a daily dose of 24 mg did not lead to any significant effect in diet treated type 2 diabetic patients.

Adrenergic beta-Agonists↗

Insulin sensitivity in patients with essential hypertension: no influence of the ACE inhibitor enalapril.

We studied the effect of an ACE inhibitor (Enalapril [ENA], 10 mg o.d.) and a calcium-channel blocker (Nitrendipine [NIT], 20 mg o.d.) on insulin sensitivity in a double-blind cross-over study. Insulin sensitivity was measured by a two-step hyperinsulinemic euglycemic clamp. Serum potassium concentrations were kept constant during the clamp procedure by means of a variable potassium infusion. Twenty patients with essential hypertension (age 35+/-12 years [mean+/-SD], BMI 31.9+/-5.0 kg m2, initial blood pressure 152+/-10/99+/-6 mmHg) were treated with ENA or NIT for 4 weeks, respectively, with a wash-out period of 3 weeks. No carry-over effects or period effects were observed. Both drugs induced a comparable decline in systolic and diastolic blood pressure (ENA - 15+/-9/ - 13+/-8 mmHg, NIT -16+/-8/- 12+/-6 mmHg). No significant change in body weight occurred with both treatments (ENA -0.4+/-2.0; NIT 0.6+/-1.1 kg). Neither drug had a significant impact on any parameter of insulin sensitivity measured (e.g. insulin sensitivity index SI: ENA 5.2+/-2.0 [basal 5.1+/-2.2], NIT 5.8+/-3.0 [basal SI 5.1+/-2.4) mi/min x m2/microU/ml). In conclusion, no significant differences between ENA and NIT on insulin sensitivity were observed. The reduction of blood pressure had no apparent effect on insulin sensitivity.

Adult↗

Value of blood pressure self-monitoring as a predictor of progression of diabetic nephropathy.

OBJECTIVE: To determine the impact of self-monitoring of blood pressure values (BP(S)) as compared with office blood pressure measurements (BP(O)) on the progression of diabetic nephropathy. DESIGN: Long-term, follow-up cohort study. SUBJECTS AND METHODS: Hypertensive, type 1 diabetic patients with overt diabetic nephropathy were investigated. Patients initially participated in a hypertension treatment and teaching programme including extensive advice on blood pressure self-monitoring. Self-monitoring and office blood pressure values were continuously assessed during the entire follow-up period. Progression of diabetic nephropathy over the study period was individually assessed as the mean decline of glomerular filtration rate (GFR) per patient per year. Baseline and follow-up parameters were included in stepwise multiple regression analyses with the decline of GFR per year as the dependent variable. RESULTS: Seventy-seven type 1 diabetic patients (37 women, 40 men) were followed for a mean period of 6.2 +/- 2.8 years (mean +/- SD; range 2-12) resulting in a total of 481 patient-years. During the follow-up period, mean BP(O) decreased from 166/95 at baseline to 154/89 mmHg during follow-up, and mean BP(S) fell from 159/93 to 138/83 mmHg. The mean decline of GFR was 4.1 +/- 5.6 ml/min per year. Loss of kidney function was significantly correlated with proteinuria, blood pressure and glycosylated haemoglobin values. In the multiple regression analyses, BP(S) predicted the loss of renal function better than BP(O) (R2 = 0.52 versus 0.42). The simple correlation between BP(S) and GFR decline was higher compared to BP(O) and GFR (r = -0.42; P < 0.0001 versus -0.33; P < 0.004). CONCLUSION: Blood pressure self-monitoring values are a better predictor of progression of diabetic nephropathy when compared with office blood pressure measurements.

Adult↗

Hepatitis B virus RNA-binding proteins associated with cytokine-induced clearance of viral RNA from the liver of transgenic mice.

Hepatitis B virus (HBV) gene expression is downregulated in the liver of HBV transgenic mice by a posttranscriptional mechanism that is triggered by the local production of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) during intrahepatic inflammation (hepatitis). The molecular basis for this antiviral effect is unknown. In this study, we identified three HBV RNA-binding liver nuclear proteins (p45, p39, and p26) the relative abundance of which correlates with the abundance of HBV RNA in response to the induction of IFN-gamma and TNF-alpha. All three proteins bind to a 91-bp element located at the 5' end of a previously defined posttranscriptional regulatory element that is thought to mediate the nuclear export of HBV RNA. The presence of p45 correlates directly with the presence of HBV RNA, being detectable under baseline conditions when the viral RNA is abundant and undetectable when the viral RNA disappears in response to IFN-gamma and TNF-alpha. In contrast, p26 is inversely related to HBV RNA, being detectable only when the viral RNA disappears following cytokine activation. Finally, p39 is constitutively expressed, and its abundance and mobility appear to be slightly increased by cytokine activation. These results suggest a model in which hepatocellular HBV RNA content might be controlled by the stabilizing and/or destabilizing influences of these RNA-binding proteins whose activity is regulated by cytokine-induced signaling pathways.

Animals↗

La autoantigen specifically recognizes a predicted stem-loop in hepatitis B virus RNA.

We recently identified three nuclear proteins (p45, p39, and p26) that bind to a 91-nucleotide (nt) RNA element between nt 1243 and 1333 in hepatitis B virus (HBV) RNA, and we showed that these proteins and HBV RNA are regulated coordinately by gamma interferon and tumor necrosis factor alpha. Purification and sequence analysis of tryptic peptides obtained from p39 revealed sequence homology to the mouse La protein. Immunoprecipitation experiments showed that p45, p39, and p26 were recognized by anti-La-specific antiserum, indicating that p45 is the full-length La protein and that p39 and p26 are likely to be proteolytic La cleavage products. Furthermore, in competition experiments we found that all three La proteins bind, in a phosphorylation-dependent manner, to the same predicted stem-loop structure located between nt 1275 and 1291 of HBV, with Kds of approximately 1.0 nM. Collectively, these results support the notion that the La protein may contribute to HBV RNA stability, constitutively and in response to inflammatory cytokines.

Amino Acid Sequence↗

Influence of continuous combined estradiol-norethisterone acetate preparations on insulin sensitivity in postmenopausal nondiabetic women.

OBJECTIVE: Estrogen-progestogen replacement therapy (HRT) may be associated with deterioration of insulin sensitivity in comparison to estrogens alone, which tend to improve insulin sensitivity in postmenopausal women. Insulin sensitivity with the use of continuous combined 17-beta estradiol/norethisterone acetate (E2/NETA) preparations has not been examined before in postmenopausal women. DESIGN: In a double-blind randomized parallel study, we evaluated the effect of 2 mg E2/1 mg NETA (high dose E2/NETA), 1 mg E2/0.5 mg NETA (low dose E2/NETA), or placebo (P) on the insulin sensitivity index (SI) in three groups (18 women/group) of postmenopausal nondiabetic women (follicle stimulating hormone [FSH] > 40 mIU/mL, mean +/- SD) aged 56 +/- 3 years, BMI 25 +/- 4 kg/m2, cholesterol 233 +/- 42 mg/dL, and triglycerides 87 +/- 36 mg/dL. Insulin sensitivity was measured by means of a two-step hyperinsulinemic euglycemic glucose clamp (insulin infusion rate, 0.25 and 1.0 mU/kg/min for 120 min each) at baseline and after 3 months of daily administration of high dose E2/NETA, low dose E2/NETA, or P. Analysis was performed assuming equivalence of start-end changes of insulin sensitivity among treatment groups (Anderson-Hauck test). RESULTS: SI was 7.7 +/- 2.9, 7.5 +/- 3.4, 6.8 +/- 2.2 at baseline and 6.3 +/- 3.0, 7.9 +/- 2.5, 7.1 +/- 3.1 mL/min/m2 per mu U/mL 3 months after the administration of high dose E2/NETA, low dose E2/NETA, and P, respectively. The low dose E2/NETA group had start-to-end changes of SI which were equivalent to the P group (0.4 [95% confidence interval [CI] -0.8; 1.7] vs. 0.4 [-0.3; 1.0]) (p = 0.02). For the high dose E2/NETA group, equivalence could not be shown with either the P (p = 0.89) or with the low dose E2/NETA group (p = 0.90). SI within the high dose E2/NETA group decreased by -1.5 (95% CI -2.7; -0.2) mL/min/m2 per mu U/mL. HbAlc decreased from 5.3 +/- 0.3 to 5.1 +/- 0.3% within the high dose E2/NETA group (p < 0.03) and remained unchanged within the low dose E2/NETA and P group. Fasting plasma glucose, fasting serum insulin, and C-peptide, as well as triglycerides and BMI were comparable among the groups at baseline and after 3 months. Total cholesterol decreased by 12% and 8% in women treated with high dose and low dose E2/NETA (p < 0.02), respectively, and remained unchanged within the P group. CONCLUSIONS: These results indicate that 3 months use of a low dose continuous E2/NETA preparation does not change insulin sensitivity in postmenopausal women. At high dose of E2/NETA, a modest decrease seems possible. The effects of E2/NETA on other parameters of carbohydrate and lipid metabolism are neutral or favorable.

Aged↗

Intramuscular versus subcutaneous injection of soluble and lispro insulin: comparison of metabolic effects in healthy subjects.

The aim of this study was to compare the glucodynamic effects of soluble insulin and the rapid acting insulin analogue insulin lispro after subcutaneous (s.c.) and intramuscular (i.m.) injection. Twelve healthy male volunteers (age 26.8 +/- 1.7 years, BMI 23.2 +/- 2.3 kg m(-2); mean +/- SD) participated in this single-centre, open-labelled, euglycaemic glucose clamp study on four different days. Soluble insulin or insulin lispro (0.2 U kg(-1)) were injected s.c. or i.m. into the thigh by syringe. The glucodynamic effects were assessed by registering the glucose infusion rates necessary to maintain blood glucose at 5.0 mmol l(-1) for the subsequent 420 min. Intramuscular injection of soluble insulin led to an earlier peak of metabolic action when compared to s.c. administered soluble insulin (tmax 138 +/- 29 vs 179 +/- 34 min; p < 0.05). The maximal metabolic effect and metabolic activity during the first 2 h after i.m. and s.c. injection of soluble insulin were comparable (GIRmax 9.7 +/- 2.3 vs 7.8 +/- 2.3 mg kg(-1) min(-1); n.s., AUC0-120min 0.60 +/- 0.18 vs 0.50 +/- 0.15 g kg(-1) 120 min; n.s.). Subcutaneous administration of insulin lispro led to a metabolic effect resembling that induced by i.m. application of soluble insulin (tmax 116 +/- 26 vs 138 +/- 29 min; n.s., GIRmax 11.1 +/- 2.3 mg vs 9.7 +/- mg kg(-1) min(-1); n.s.). However, the overall metabolic response during the first 2 h after injection was higher with s.c. insulin lispro (AUC0-120min 0.81 +/- 0.26 vs 0.60 +/- 0.18 g kg(-1) 120 min; p < 0.05). The glucodynamic activity of i.m. applied insulin lispro was comparable to that of lispro s.c.. Following i.m. injection of soluble insulin, the metabolic activity peaked more rapidly than with s.c. administration. In contrast, the metabolic effect of insulin lispro was similar with either route. The time-action profile of i.m. injected soluble insulin lies between that of s.c. applied soluble insulin and insulin lispro.

Adult↗

Simulated postaggression metabolism in healthy subjects: metabolic changes and insulin resistance.

Postaggression metabolism (PAM) is difficult to study in critically ill patients. The objective of this study was to simulate PAM in healthy subjects to quantify insulin sensitivity under these conditions. Six healthy men (age, 24 +/- 1 years; body mass index, 22.0 +/- 0.7 kg/m2 [mean +/- SE]) received an intravenous (i.v.) infusion of insulin-counteracting hormones (epinephrine 100 ng/kg/min, glucagon 16 ng/kg/min, hydrocortisone 5 microg/kg/min, and growth hormone [GH]-releasing hormone 50 microg/h) for 4 hours in addition to glucose (270 mg/kg/h). Control experiments used glucose only. In additional experiments, insulin sensitivity was measured by a two-step hyperinsulinemic glucose clamp with and without concomitant hormone infusion (insulin infusion rate, 2.5 and 5.0 mU/kg/min for hormone infusion or 1.0 and 2.5 mU/kg/min for control experiments). Plasma stress hormones reached levels comparable to severe PAM (epinephrine, 1,085 +/- 89 pg/mL; glucagon, 1,100 +/- 114 pg/mL; cortisone, 1,004 +/- 32 ng/mL; and GH, 20.6 +/- 6.1 pg/mL) in the hormone infusion experiment. This resulted in hyperglycemia and hyperinsulinemia (steady-state blood glucose, 19.7 +/- 0.4 mmol/L; serum insulin, 352 +/-8 pmol/L) in comparison to the control experiments with glucose infusion only (maximal blood glucose 7.2 +/- 0.8 mmol/L; serum insulin, 110 +/- 16 pmol/L). The insulin sensitivity index (S(I)) was 88% +/- 6% lower during hormone infusion (0.6 +/- 0.4 mL/min/m2/microU/min) compared with the control experiments (4.5 +/- 1.3 mL/min/m2/microU/min). Infusion of insulin-counteracting hormones at high doses allows simulation of the changes in carbohydrate metabolism observed in PAM in healthy subjects. The observed profound decrease in insulin sensitivity explains the hyperglycemia observed in nondiabetic critically ill patients. With this experimental setup, standardized investigations of therapeutic interventions in PAM should be possible.

Adult↗

Implications of the traditional and the new ACSM physical activity recommendations on weight reduction in dietary treated obese subjects.

OBJECTIVE: To assess the acceptance of the traditional American College of Sports Medicine (ACSM) exercise recommendation (20-60 min of vigorous exercise at least three times per week) and of the new, broader Centers for Disease Control (CDC)/ACSM physical activity recommendation (30 min of moderate intensity activities on most days of the week) in an obese population and to elucidate the implications of meeting these recommendations on weight reduction during dietary treatment. DESIGN: Prospective dietary intervention study of 1000 kcal diet daily. SUBJECTS: 109 obese subjects (age: 45.6 +/- 13.1 y, body mass index (BMI): 38.1 +/- 6.0 kg/m2, (Female/Male: 81/19%) MEASUREMENTS: The time spent in moderate (3-6 MET, metabolic equivalents) and vigorous (6-10 MET) physical activities was assessed by use of the Stanford-7-Day-Physical-Activity-Recall-Questionnaire, with subsequent allocation of the subjects to one of three physical activity groups: meeting the traditional recommendation (TR), the new recommendation (NR) or neither of both (SED, sedentary subjects). Physical activity level, physical activity energy expenditure, total energy expenditure (based upon the questionnaire) and resting metabolic rate (by standard equation) were estimated at baseline. Body weight was determined at baseline and after a mean of 16.3 weeks of dietary treatment. RESULTS: The new, broader recommendation was met by twice as many of the obese subjects (34%) as was the traditional recommendation (17%). Weight reduction at follow up (-8.2 +/- 6.5 kg, 16.3 +/- 4.3 weeks, mean +/- s.d.) was positively correlated with the physical activity level at baseline (r = 0.49, P < 0.001). Meeting either the traditional or the new recommendation was associated with greater weight loss [-11.9 +/- 8.5 kg (TR) and -10.1 +/- 6.4 kg (NR), respectively, not statistically significant (NS)] as compared to being sedentary [-6.5 +/- 5.2 kg (SED), P < 0.05 vs both NR and TR]. CONCLUSIONS: Not only participation in vigorous exercise, but also regular engagement in moderate intensity physical activities, as recently recommended by the CDC/ACSM, predicts greater weight reduction during dietary treatment, compared to being sedentary. The new, broader physical activity recommendation appears to be more readily accepted by obese subjects than the former ACSM recommendation on exercise training.

Adult↗

Electrocardiographic changes during insulin-induced hypoglycemia in healthy subjects.

Hypoglycemia is associated with alterations of the ECG, a phenomenon which might be used for the development of a hypoglycemia detection device. We investigated the reproducibility and magnitude of ECG alterations during insulin-induced hypoglycemia in nine healthy volunteers. The subjects were studied twice with an identical study protocol on two different study days. During hypoglycemia frequent ECG recordings were done with a conventional 12 lead ECG. S.c. injection of 0.15 U/kg of regular insulin induced a fourfold increase in insulinemia on both study days as well as a mean decline in blood glucose by 1.6 mmol/l to a minimum of 2.8 mmol/l within 60 min after injection. Blood potassium levels declined by a mean of 0.25 mmol/l to minimal values of 3.69 mmol/l. On both study days, a progressive flattening of the T-waves was observed during the experiments. R-waves remained constant leading to an increase in RT ratios by at least 50% in comparison to baseline values. These changes were most pronounced in leads I, V3, V5 and V6. The magnitude and reproducibility of the observed ECG changes during hypoglycemia may allow the development of a hypoglycemia detection device.

Adult↗

Non-evidence-based concepts are still established in the treatment of IDDM.

Medicine is and always has been full of unproven concepts. However, when they are frequently used in clinical practice, they seem established and are therefore seldom questioned. In his book 'Follies and fallacies in medicine' (Glasgow, The Tarragon Press, 1989) Peter Skrabanek clearly proposed a way to improve the quality of medicine by being chronically skeptical towards all 'established' concepts. By citing Bertold Brecht he proposed 'scepticemia' as a major tool to speed up the progress in medicine: 'The chief cause of poverty in science is imaginary wealth. The chief aim of science is not to open a door to infinite wisdom but to set a limit to infinite error.' In this article we will try to analyze the evidence of the three so-called cornerstones of diabetes therapy diet, exercise and insulin--with regard to their efficacy in reaching the goals of treatment in type 1 (insulin-dependent) diabetes.

Diabetes Mellitus, Type 1↗

Insulin resistance and the effect of insulin on blood pressure in essential hypertension.

The aim of this study was to investigate the effect of 2 weeks of insulin administration on blood pressure and to simultaneously measure insulin sensitivity and insulin-induced vasodilatation in obese hypertensive patients. In a prospective, randomized, double-blind, crossover study (study 1), 23 obese, untreated, nondiabetic, hypertensive patients received either neutral protamine Hagedorn (NPH) insulin (0.3 U/kg body wt per day) or placebo subcutaneously for 2 weeks (washout period, 2 weeks). Office and 24-hour blood pressure values were measured at the beginning and end of each treatment period. In an open-label study (study 2), 8 obese hypertensive patients and 10 healthy control subjects underwent a 3-step hyperinsulinemic, euglycemic glucose clamp (step 1, 0.5; step 2, 2.5; step 3, 5.0 mU x kg(-1) x min(-1) [120 minutes each]). Leg blood flow (LBF) was measured by venous occlusion plethysmography. Insulin administration decreased mean+/-SD office blood pressure from 131+/-13 to 128+/-12 mm Hg (placebo, 132+/-13 and 132+/-13 mm Hg; P<0.05 between final examinations) and mean+/-SD 24-hour blood pressure by -3.3+/-6.9 mm Hg (placebo, +0.7+/-4.6 mm Hg; P<0.05). Insulin infusion increased LBF significantly in the healthy controls but not in obese insulin-resistant hypertensive subjects. Obese hypertensive patients are resistant to the effects of insulin with regard to both glucose uptake and vasodilatation. Administration of insulin exerts a small blood pressure-lowering effect in these patients. These data strongly argue against the postulated pressor action of insulin in essential hypertension.

Administration, Cutaneous↗