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Biomedical subjects

O Ziegler

Publications and source records attributed to O Ziegler.

At least 37 records · Page 2Linked to original sources
PubMed2000

No acute response of leptin to an oral fat load in obese patients and during circadian rhythm in healthy controls.

This study was done to elucidate the relationship between postprandial leptin and obesity, and the possible influence of the circadian rhythm on the dynamic leptin response to an oral fat load (OFLT). In experiment 1, we measured the leptin and insulin responses to an oral fat load in 16 non-diabetic obese subjects and in 16 healthy controls, matched for age and gender. In experiment 2, we measured the leptin and insulin responses to an OFLT according to the time of fat load ingestion: 0700 h (diurnal (D) test) or 2200 h (nocturnal (N) test) in nine normal-weight healthy males. Baseline leptin concentration was correlated with the body mass index, body fat mass and percentage of body fat mass in both experiments. The leptin concentrations were higher in women than in men (P<0.001). In experiment 1, the leptin concentrations were higher in obese subjects than in controls, but did not change over time in either group. The plasma insulin concentrations at baseline and during the postprandial state, as well as the area under the curve (AUC) of insulin, were higher in obese subjects than in controls (P<0.05-0. 0001). There was no correlation between postprandial insulin responses and postprandial leptin responses in either obese or control groups. In experiment 2, leptin (D vs N, 2.9+/-1.4 vs 2. 9+/-1.0 ng/ml) and insulin (D vs N, 41+/-18 vs 25+/-9 pmol/l) concentrations were similar at the beginning of the D and N tests after a 10 h fast. The leptin concentrations did not change after D or N tests and were not statistically different for D and N tests. Our results indicate that the leptin concentration in healthy controls and in obese patients is not acutely influenced by a high fat load.

Adult↗
PubMed2000

[Drug treatment of obesity and type 2 diabetes].

Drug therapy of obesity (DTO) has not been extensively used in diabetic patients so far, although excessive adipose mass largely contributes to insulin resistance which characterizes this disease together with insulin secretion failure. Orlistat is the sole currently available treatment, but several other new treatments are under investigation, such as sibutramine already marketed in other countries. Both drugs were found to be efficient in long term studies (1 year). However it is puzzling to note that weight loss induced by the drug as well as during placebo treatment is less pronounced in diabetic patients as compared with non diabetic subjects. Short term studies had already documented a lower response to DTO in diabetic patients by 2-fold. The reasons for this weight loss resistance in diabetics under DTO remain unclear and could be linked with metabolism. A weight loss > or = 5% initial body weight is required to obtain a significant lowering of HbA1c. Weight variations (weight delta > or = 5-10% initial weight) and results on glucose control (HbA1c delta > or = 0.5% after 3 to 6 months, or fasting blood glucose delta > or = 1 mmol/l within a few weeks) allow to define good DTO responders which should preferentially be eligible for this treatment. A decisional diagram is suggested.

Blood Glucose↗
PubMed2000

[Physiopathology of obesity. Dietary factors, and regulation of the energy balance].

Energy balance and macronutrient balance are the cornerstones upon which any theories of obesity must be built. Obesity can only occur when energy intake remains higher than energy expenditure for an extended period of time. However the macronutrient composition of the diet can also affect energy balance. Fat is a key nutrient because it is poorly regulated at both the level of consumption and oxidation. Psychological and behavioural profiles of obese subjects are clearly important because they can affect food choice and eating patterns. The role of eating frequency and circadian distribution of food is still debated. Eating disorders could be implicated in the development of obesity, but it is uncertain whether obesity is a direct result or a cause of the eating disorder. There are strong evidence to suggest that dietary restraint is associated with loss of dietary control and excessive eating. Early stages of fat storage involve expansion of existing adipocytes (hypertrophy) and later stages involve the recruitment of new adipocytes (hyperplasia). The mechanisms controlling the transformation of preadipocyte could also involve specific dietary components such as polyunsaturated fatty acids or proteins. The age of adiposity rebound, that is a risk factor for later obesity has been found significantly younger in children consuming a high protein diet. These factors could be involved during early infancy or even in utero, according to the hypothesis of fetal programming of adult diseases. There is a need for more longitudinal studies on the role of macronutrient composition, food choice or eating disorders, especially among children, teenagers and young adults.

Adipose Tissue↗
PubMed1999

Glycation of apolipoprotein E impairs its binding to heparin: identification of the major glycation site.

The increased glycation of plasma apolipoproteins represents a possible major factor for lipid disturbances and accelerated atherogenesis in diabetic patients. The glycation of apolipoprotein E (apoE), a key lipid-transport protein in plasma, was studied both in vivo and in vitro. ApoE was shown to be glycated in plasma very low density lipoproteins of both normal subjects and hyperglycemic, diabetic patients. However, diabetic patients with hyperglycemia showed a 2-3-fold increased level of apoE glycation. ApoE from diabetic plasma showed decreased binding to heparin compared to normal plasma apoE. The rate of Amadori product formation in apoE in vitro was similar to that for albumin and apolipoproteins A-I and A-II. The glycation of apoE in vitro significantly decreased its ability to bind to heparin, a critical process in the sequestration and uptake of apoE-containing lipoproteins by cells. Diethylenetriaminepentaacetic acid, a transition metal chelator, had no effect on the loss of apoE heparin-binding activity, suggesting that glycation rather than glycoxidation is responsible for this effect. In contrast, glycation had no effect on the interaction of apoE with amyloid beta-peptide. ApoE glycation was demonstrated to be isoform-specific. ApoE(2) showed a higher glycation rate and the following order was observed: apoE(2)>apoE(4)>apoE(3). The major glycated site of apoE was found to be Lys-75. These findings suggest that apoE is glycated in an isoform-specific manner and that the glycation, in turn, significantly decreases apoE heparin-binding activity. We propose that apoE glycation impairs lipoprotein-cell interactions, which are mediated via heparan sulfate proteoglycans and may result in the enhancement of lipid abnormalities in hyperglycemic, diabetic patients.

Aged↗
PubMed1999

[Insulin in the treatment of type 2 diabetes].

Insulin use in NIDDM is a frequent situation. Many acute clinical circumstances justify a transient insulin therapy including ketoacidosis decompensation or hyperosmolar state and severe intercurrent diseases. The problem is more complex when glycemic control is no longer obtained despite maximal doses of oral treatment. Type 2 diabetes is then defined as an insulin-requiring diabetes. There is actually no consensus, but lots of arguments advocate an intensive insulin therapy based on multiple daily injections in this clinical state. However, when patient's overweight is important or if the clinical context is unfavourable, conventional insulin therapy or combined treatment using bedtime insulin and daytime oral agents may be tried.

Blood Glucose↗
PubMed1999

Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine.

BACKGROUND: Very-low-calorie diets are a well established method to achieve substantial short-term weight loss in obese patients, but long-term maintenance of the weight loss is very disappointing. A combined very-low-calorie diet and pharmacologic approach could be an effective means of prolonging its benefits. PATIENTS AND METHODS: Eligible patients had a body-mass index greater than 30 kg/m2; those who lost 6 kg or more during a 4-week treatment with a very-low-calorie diet were randomly assigned to 1 year of treatment with sibutramine (10 mg) or identical placebo. RESULTS: In an intention-to-treat analysis, mean (+/-SD) absolute weight change at 1 year (or study endpoint) was -5.2 (+/-7.5) kg in the 81 patients in the sibutramine group and +0.5 (+/-5.7) kg in the 78 patients in the placebo group (P = 0.004). When compared with their weight at study entry (before the very-low-calorie diet), 86% of patients in the sibutramine group had lost at least 5% of their weight, compared with only 55% of those in the placebo group (P <0.001) at the study endpoint. Similarly, at month 12, 75% of subjects in the sibutramine group maintained at least 100% of the weight loss achieved with a very-low-calorie diet, compared with 42% in the placebo group (P <0.01). CONCLUSION: Following a very-low-calorie diet, sibutramine is effective in maintaining and improving weight loss for up to 1 year.

Adult↗
PubMed1999

Delayed changes in postprandial lipid in young normolipidemic men after a nocturnal vitamin A oral fat load test.

The oral fat load tests (OFLT) used to study postprandial lipemia are generally conducted during the day. A nocturnal fat load test could be convenient and physiologically more appropriate. We have therefore compared the lipemic responses of 9 normolipidemic young men to OFLT given at 2200 h (nocturnal) and at 0700 h (diurnal). Triglyceride and retinyl palmitate concentrations were measured for 10 h. Peak plasma concentrations or areas under curves (AUC) for triglyceride after the diurnal and nocturnal tests were not significantly different [2.17 +/- 0.78 (diurnal) vs. 2.04 +/- 0.87 mmol/L (nocturnal) and 13.12 +/- 4.45 (diurnal) vs. 13.74 +/- 5.79 mmol/(L. h) (nocturnal)]. Peak plasma concentrations and AUC retinyl palmitate for the two tests were not different [1.71 +/- 0.69 (diurnal) vs. 1.42 +/- 0.66 mg/L (nocturnal) and 7.17 +/- 3.98 (diurnal) vs. 6.63 +/- 4.23 mg/(L. h) (nocturnal)]. The diurnal triglyceride peak occurred significantly earlier (4.3 +/- 1.2 h) than the nocturnal peak (5.8 +/- 1.7 h, P < 0.05). We have developed a model using only three sample time points to predict AUC [triglyceride at 0 h, triglyceride at average peak-time (4 h for diurnal and 6 h for nocturnal tests), and triglyceride at 10 h], thus reducing the number of blood samples. The predicted AUC was well correlated with the total AUC after nocturnal OFLT (r = 0.98, P < 0.0001). The nocturnal test appeared to be well tolerated by the subjects. The three-point simplified protocol may well be suitable for studies on large groups of subjects.

Adult↗
PubMed1999

Diagnosis of lipid malabsorption in patients with chronic pancreatitis: a new indirect test using postprandial plasma apolipoprotein B-48.

OBJECTIVE: This study was done to evaluate a new test for fat malabsorption caused by chronic pancreatitis. Postprandial plasma apolipoprotein B-48 was measured as an indicator of the intestinal assimilation of exogenous lipid. METHODS: Twenty-three patients with chronic pancreatitis, including 19 insulin-treated diabetic patients, were compared with 14 healthy subjects and seven type-1 diabetic patients. Each was given a test meal containing 40 g lipid; the triglyceride apolipoprotein B-48 concentrations in chylomicrons were determined 240 min later. RESULTS: The postprandial chylomicron apolipoprotein B-48 concentrations in the three groups were statistically different at 240 min: pancreatitis versus controls, p < 0.01, and pancreatitis versus type-1 diabetes subjects, p < 0.01. The delta plasma apo B-48, the change in apolipoprotein B-48 between 0 and 240 min, was significantly smaller in chronic pancreatitis patients than in controls (p < 0.001) and type-1 diabetes subjects (p < 0.001). The sensitivity of the test was better than 89% for a delta apo B-48 threshold value of 0.42 mg/dl. CONCLUSIONS: This new indirect test is relatively simple to use and could be practical for evaluating exogenous lipid malabsorption due to chronic pancreatitis.

Adult↗
PubMed1999

Comparison of metabolic deterioration between insulin analog and regular insulin after a 5-hour interruption of a continuous subcutaneous insulin infusion in type 1 diabetic patients.

An interruption of continuous sc insulin infusion (CSII) of the insulin analog lispro should result in a more rapid metabolic deterioration of type 1 diabetic patients because of its pharmacokinetic characteristics. We analyzed the metabolic changes occurring during a 5-h interruption of CSII and the 5 h after restarting the pump in 10 type 1 diabetic patients. The study was a randomized, cross-over, open label design comparing insulin analog [Lispro (LP)] and regular insulin [Velosuline (VE)]. Plasma glucose, free insulin, glucagon, betahydroxybutyrate (beta-OHB), and nonesterified fatty acids (NEFA) were measured every hour from 0700 h (time zero) to 1700 h (600 min). After stopping CSII, the plasma glucose level was significantly higher in the LP group than in the VE group (P < 0.05-0.01). The plasma free insulin level decreased significantly with the two treatments, but was significantly lower with LP than with VE (P < 0.05-0.01). Plasma NEFA increased more rapidly and was significantly higher in the LP group than in the VE group (P < 0.01-0.05). Plasma beta-OHB increased earlier with LP, but was not statistically different between the treatments. After restarting the pump, plasma glucose decreased with LP, but continued to increase with VE, and the plasma free insulin peak occurred earlier and was greater with LP than with VE (P < 0.05). Plasma NEFA and beta-OHB levels decreased significantly with the two treatments, but more dramatically with LP treatment. Thus, a short interruption of Lispro in CSII is associated with an earlier, greater metabolic deterioration, but Lispro corrected this metabolic deterioration more effectively.

3-Hydroxybutyric Acid↗
PubMed1999

Increased ability of LDL from normolipidemic type 2 diabetic women to generate peroxides.

BACKGROUND: We assessed the ability of LDL from 30 type 1 diabetic patients (18 men, 12 women), 65 type 2 diabetic patients (35 men, 30 women), and 35 controls (19 men, 16 women) to generate peroxides. The men and women in the diabetic groups were studied separately and matched for age, body mass index, duration of diabetes, glycohemoglobin, and conventional lipid characteristics according to the presence or absence of hyperlipidemia. METHODS: The ability of LDL to form peroxides was assessed by measuring the thiobarbituric acid-reactive substances corrected for LDL-cholesterol [ratio of malondialdehyde (MDA) to LDL-cholesterol]. LDL particle size was expressed as the ratio of LDL-cholesterol to apolipoprotein B (LDL-cholesterol/apoB). RESULTS: The MDA/LDL-cholesterol ratio was higher in type 1 and type 2 diabetic patients with hyperlipidemia than in controls. The MDA/LDL-cholesterol ratio was also higher in type 2 normolipidemic women than in controls (P <0.01). The LDL-cholesterol/apoB ratio was lower in type 2 diabetic women than in type 2 diabetic men (P <0.05). The MDA/LDL-cholesterol ratio was negatively correlated with the LDL-cholesterol/apoB ratio (r = -0.78, P <0.001) in hyperlipidemic type 1 (not type 2) diabetic patients. In normolipidemic type 2 diabetic patients, the MDA/LDL-cholesterol ratio was also negatively correlated with the LDL-cholesterol/apoB ratio (r = -0.75, P <0.001) because of the highly significant negative correlation in type 2 diabetic women (r = -0.89, P <0.01). CONCLUSIONS: LDL from well-controlled type 2 diabetic women is smaller and more prone to form peroxides. This could explain why diabetic women are at greater risk of cardiovascular disease.

Adult↗
PubMed1999

Severity of diabetic retinopathy is linked to lipoprotein (a) in type 1 diabetic patients.

To determine the relationship between plasma Lp(a) concentration and the risk of developing diabetic retinopathy, 341 Type 1 diabetic patients underwent an annual retinal fluorescein angiography and were assigned to one of 3 groups according to the stage of their diabetic retinopathy: no retinopathy (NR), non-proliferative diabetic retinopathy (N-PDR), or proliferative diabetic retinopathy (PDR). One hundred and twenty-three Type 1 diabetic patients had no retinopathy, 188 had N-PDR and 30 had PDR. The ages of the three groups and the duration of diabetes were significantly different. Hypertension, microalbuminuria and diabetic nephropathy were more frequent in PDR than in NR or N-PDR (p < 0.0001). Plasma HbA1c was higher in PDR than in NR or N-PDR (p < 0.01). Type 1 patients who had been diabetic for at least 20 years included 30 NR, 108 N-PDR and 24 PDR. Type 1 diabetic patients with PDR had microalbuminuria and macroproteinuria more frequently than other patients (p < 0.0001 and 0.01, respectively). Type 1 diabetic patients with PDR had the highest median plasma Lp(a) and the highest frequency of Lp(a) above 30 mg/dl (p < 0.05). Multivariate analysis carried out in Type 1 diabetic patients with a duration of diabetes of at least 20 years showed that microproteinuria, HbA1c and Lp(a) accounted significantly for 21% of variance in retinal status. Lp(a) above 30 mg/dl was related to the risk of developing PDR (OR = 8.40, p < 0.05). Lipoprotein(a) appears to be associated with the severity of diabetic retinopathy in Type 1 diabetic patients, and particular attention should be paid to those with Lp(a) above 30 mg/dl and pre-proliferative retinopathy.

Adult↗
PubMed1998

Blood glucose control on Sunday in IDDM patients: intensified conventional insulin therapy versus continuous subcutaneous insulin infusion.

We have assessed the capacity of continuous subcutaneous insulin infusion (CSII) to maintain good blood glucose metabolic control on Sundays, when waking is delayed, with reference to intensified conventional insulin therapy by multiple daily injections (MDI). The study lasted 3 weeks, including 3 week-ends. A total of 20 IDDM patients were selected for metabolic control: ten were treated by CSII and ten by MDI. Blood glucose was determined at least three times a day (fasting on waking, pre-lunch and pre-dinner). The times of blood glucose determinations and their values were recorded in a memory reflectance meter. Waking, the first blood glucose measurement and the first insulin injection (MDI) or bolus (CSII) were about 1 h later on Sundays than on a weekday (44 +/- 4 min in MDI group, P < 0.04; and 59 +/- 7 min in CSII group, P < 0.02). The times of the pre-lunch and pre-dinner blood glucose determinations were not significantly different. The mean waking and pre-lunch blood glucose values of the MDI group were higher on Sundays (11.5 +/- 3.8 and 9.7 +/- 4.5 mmol/l) than on weekdays (8.7 +/- 2.3 and 7.1 +/- 2.5 mmol/1)(P < 0.01). The pre-prandial blood glucose levels of the CSII group on Sundays and weekdays were not statistically different at any time. Changes in the waking time and the subsequent delay in the first insulin bolus on Sunday may alter blood glucose control in patients on MDI, but CSII allows such changes without any glycemic side effects.

Adult↗
PubMed1998

[The "second atherogenic phenotype" or the role of insulin resistance in vascular risk].

LDL cholesterol is the principal vascular risk factor but it is not the only one. Paradoxically, the atherogenic role of triglycerides or that of metabolic abnormalities of triglyceride-rich lipoproteins has been underestimated. It is convenient to use the term "second atherogenic phenotype" for those phenotypes associating a hypertriglyceridaemia, a low HDL-cholesterol, a moderate increase in LDL cholesterol composition (the small dense LDL). Insulin resistance could be the common denominator of these different abnormalities, increasing the production of triglyceride-rich lipoproteins and decreasing their catabolism. In this concept which remains hypothetical, insulin resistance would appear to be a vascular risk factor. Its role could be direct or indirect by the many risk factors described in the syndrome X. The taking into account of this second atherogenic phenotype of hyperlipidaemia has obvious therapeutic implications because of the choice of diet and treatment. Though stains represent the treatment of choice of high LDL cholesterol, the fibrates are useful in the treatment of hypertriglyceridaemia, low HDL-cholesterol and small and dense LDL. Therapeutic trials comparing the efficacy of statins and fibrates with respect to cardiovascular and global mortality should provide future information in this debate.

Arteriosclerosis↗
PubMed1998

Lipoatrophic diabetes mellitus treated by continuous subcutaneous insulin infusion.

This case report evaluated continuous subcutaneous insulin infusion (CSII) in a 50-year-old Caucasian woman who suffered from partial lipodystrophy and severely insulin-resistant diabetes mellitus. Intensive insulin therapy (three daily injections) failed to provide good metabolic control (HbA1c ranging from 10 to 12%). Even though the patient had very thin subcutaneous tissue, CSII was initiated and proved highly efficient, improving blood glucose control considerably (HbA1c ranging from 7.5 to 8.5%), but with no decrease in the daily insulin requirement (2 IU/kg/day). Plasma triglycerides were also greatly improved (from 16.5 to 3.7 mmol/l). Thus, this study indicates that CSII is suitable for patients with lipoatrophy and insulin-resistant diabetes mellitus.

Adolescent↗