CONGENITAL GENERALIZED LIPODYSTROPHY AND EXPERIMENTAL LIPOATROPHIC DIABETES IN RABBITS TREATED SUCCESSFULLY WITH FENFLURAMINE

1977 ◽  
Vol 85 (2) ◽  
pp. 436-448 ◽  
Author(s):  
Olav Trygstad ◽  
Irene Foss
Keyword(s):  
Fasting Blood Glucose ◽  
Serum Triglyceride ◽  
Profuse Perspiration ◽  
Congenital Generalized Lipodystrophy ◽  
Lipoatrophic Diabetes ◽  
Serum Triglyceride Concentration ◽  
Daily Dose ◽  
The Central Nervous System ◽  
Increased Sensitivity ◽  
Resistance To Insulin

ABSTRACT Lipoatrophic diabetes has been produced in rabbits by injection of a fraction prepared from the urine from patients with congenital generalized lipodystrophy. Both these conditions are considered to be hypothalamic syndromes. The animals, and a patient with congenital generalized lipodystrophy and latent diabetes were treated with the dopamine receptor blocker, pimozide, for 4 and 17 months, respectively. The results were discouraging even though the patient got a daily dose of 16 mg pimozide. Fenfluramine has a lowering effect on brain serotonin, and peripheral effects on glucose and triglyceride metabolism. This drug improved the general condition of the rabbits with lipoatrophic diabetes, as well as that of the patient with congenital generalized lipodystrophy. The rabbits became normoglycaemic and insulin sensitive. In the patient a normalization of the urinary excretion of the serotonin metabolite 5-OH-indole acetic acid was observed. His voracious hunger and profuse perspiration were reduced, the hyperkeratotic layer of the skin peeled off, and the pigmentations of the skin decreased. There was observed an improvement of ALAT and ASAT, normalization of the fasting blood glucose, and increased sensitivity to exogenous insulin. After 11 months of 200 mg fenfluramine daily addtitional administration of 2 g clofibrate per day produced normalization of the serum triglyceride concentration and a marked reduction of the resistance to insulin. Three more patients with congenital generalized lipodystrophy, two of whom have manifest diabetes, have now started treatment with fenfluramine and are improving. The rabbits got relapse of their lipoatrophic diabetes when the fenfluramine treatment was stopped. It is suggested that a disturbance in the serotonin metabolism of the central nervous system may be of pathogenetic importance in congenital generalized lipodystrophy.

scholarly journals Urinary Paraben Concentration and Its Association with Serum Triglyceride Concentration in 2013-2014 NHANES Participants: A Cross-Sectional Study

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Rebecca Pazos ◽  
Cristina Palacios ◽  
Adriana Campa
Keyword(s):  
Geometric Mean ◽  
Serum Triglyceride ◽  
Health Impact ◽  
Cross Sectional Study ◽  
Urinary Concentration ◽  
Sectional Study ◽  
Cross Sectional ◽  
Endocrine Disrupting ◽  
Serum Triglyceride Concentration ◽  
Hispanic White

Background. Alkyl esters of para-hydroxybenzoic acid, colloquially known as parabens, are types of preservatives found in multiple foodstuffs, pharmaceuticals, and personal care products to which Americans are exposed daily. It is unclear if parabens exhibit endocrine-disrupting properties. Parabens may interact with triglycerides in adipose tissue and impact lipid metabolism. Objective. To evaluate the association between urinary paraben concentrations and serum triglyceride concentrations. Design. A cross-sectional study. Setting. The Mobile Examination Centers affiliated with 2013-2014 NHANES. Participant(s). 827 adults (20 years or older) affiliated with the 2013-2014 NHANES. Intervention(s). None. Main Outcome Measure(s). Triglyceride levels were associated with urinary paraben concentrations (methyl, ethyl, and propyl) using a hierarchical multiple regression, adjusting for ethnicity/race, gender, BMI, and age. Unadjusted results are also reported. Results. The geometric mean of the urinary concentration of methylparaben, ethylparaben, and propylparaben was 57.100, 2.537, and 6.537 ng/ml, respectively. Triglyceride concentrations were inversely associated with methylparaben (β = −0.092, P=0.07), ethylparaben (β = −0.066, P=0.045), and propylparaben (β = −0.076, P=0.025). Being female, non-Hispanic White, and non-Hispanic Black were associated with decreasing triglyceride levels in the presence of methylparaben, ethylparaben, and propylparaben, and age, BMI, and being male were associated with increasing circulating triglycerides. Conclusion. Despite the potential detrimental effects of parabens on triglycerides, our results suggest that urinary excretions of methylparaben, ethylparaben, and propylparaben are associated with lower concentrations of circulating triglycerides in certain populations. Further research is needed to confirm the mechanisms and health impact of this relationship.

Modification of Insulin Resistance

1956 ◽  
Vol 102 (428) ◽  
pp. 576-588 ◽  
Author(s):  
Edward Marley
Keyword(s):  
Deep Coma ◽  
Insulin Dosage ◽  
Insulin Resistant ◽  
Significant Difference ◽  
High Insulin ◽  
Insulin Coma ◽  
The Central Nervous System ◽  
Resistance To Insulin ◽  
High Doses ◽  
Special Instance

Sakel (1938a) drew attention to the difficulty of establishing satisfactory comas in a minority of patients attending for Deep Insulin therapy. This phenomenon has since been confirmed by other workers including Tillim (1938) whose patient received 500 units of insulin without the production of deep coma, by Hall (1940) who reported an instance in which 1,000 units of insulin was equally unsuccessful, by Reznikoff and Scott (1942) who described how neither 120 nor 1,000 units of insulin when injected intravenously produced any significant difference in hypoglycaemia in insulin resistant patients, and more recently by Fogarty (1953) whose case required 5,000 units of insulin for the production even of sopor. Other recorded examples of resistance to massive doses of insulin include those of Bantinget al.(1938) and Tennent (1944).Various explanations of this perverse response to insulin have been formulated, including that of Jones (1939) who proposed that resistance to insulin was both a problem of true insulin insensitivity and also of an anomalous response of the central nervous system to hypoglycaemia. Medunaet al.(1942) preferred to ascribe it to anti-insulin factors in the blood, but a more interesting interpretation derived from Freudenberg (1952) who suggested that if the effects of high insulin dosage employed in insulin coma treatment were regarded as a special instance of a stress response, then the fluctuations and differences in response could be equated in terms of the General Adaptation Syndrome of Selye. High doses were thus an index of an effective “alarm stage” characterized by a discharge from plentiful adrenocortical reserves.

Dietary Sulfur-Containing Amino Acids Are Associated with Higher Prevalence of Overweight/Obesity in Northern Chinese Adults, an Internet-Based Cross-Sectional Study

2018 ◽  
Vol 73 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Yan-chuan Li ◽  
Yu-zheng Li ◽  
Rui Li ◽  
Li Lan ◽  
Chun-long Li ◽  
...  
Keyword(s):  
Amino Acids ◽  
Low Density Lipoprotein ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Postprandial Glucose ◽  
Lipid Profiles ◽  
Model Assessment ◽  
Cross Sectional ◽  
Sulfur Containing

Background/aims: Elevation of plasma sulfur-containing amino acids (SAAs) is generally associated with higher body mass index (BMI) and unfavorable lipid profiles. It is not known how dietary SAAs relate to these associations in humans. Methods: A convenient tool named internet-based dietary questionnaire for Chinese (IDQC) was used to estimate dietary SAAs intake. A total of 936 participants were randomly recruited and asked to complete the IDQC. Furthermore, 90 subjects were randomly selected to perform a subgroup study. The associations between dietary SAAs and prevalence of obesity, lipid profiles, and status of insulin resistance (IR), inflammation and oxidative stress were assessed. Results: Dietary total SAAs and cysteine of overweight/obese participants were significantly higher. Dietary total SAAs and cysteine were positively associated with BMI and waist circumference. Higher dietary total SAAs were associated with higher prevalence of overweight/obesity. Higher dietary total SAAs and cysteine also associated with higher serum triglyceride (total cholesterol), low density lipoprotein, fasting blood glucose, 2 h-postprandial glucose, and homeostasis model assessment of IR. In the subgroup study, positive associations between dietary SAAs and inflammation biomarkers were also observed. Conclusions: Dietary SAAs are associated with higher prevalence of overweight/obesity, unfavorable lipid profiles and status of IR, and inflammation.

Fluorometric estimation of triglycerides in serum by a modification of the method of Bucolo and David.

1977 ◽  
Vol 23 (2) ◽  
pp. 286-288 ◽  
Author(s):  
E B Rietz ◽  
G G Guilbault
Keyword(s):  
Blood Serum ◽  
Spectrophotometric Method ◽  
Serum Triglyceride ◽  
Excitation Wavelength ◽  
Free Glycerol ◽  
Fluorometric Method ◽  
Nadh Fluorescence ◽  
Instrument Response ◽  
Serum Triglyceride Concentration

Abstract An enzymic, flurometric method is described for determination of triglycerides (and glycerol) in blood serum, a modification of the method of Bucolo and David [Clin. Chem. 19, 476 (1973)]. Commercially available reagent kits are used. The rate of disappearance of NADH fluorescence at 460 nm (excitation wavelength, 365 nm) is monitored and related to serum triglyceride concentration, corrected for the content of free glycerol. We compared the results obtained fluorometrically to the ultraviolet spectrophotometric Boehringer Neutral Fat method used at Gentofte Hospital, Copenhagen. Instrument response and concentration were linearly related in the range 0.27 to 2.7 mmol of triglycerides per liter of serum with the fluorometric method. The CV was 0.9% for the fluorometric method, 3.7% for the spectrophotometric procedure. The fluorometric method requires less reagents, time, and calculations than does the spectrophotometric method.

scholarly journals Human sex hormone-binding globulin does not provide metabolic protection against diet-induced obesity and dysglycemia in mice

2018 ◽  
Vol 7 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Yael Sofer ◽  
Nava Nevo ◽  
Michal Vechoropoulos ◽  
Gabi Shefer ◽  
Etty Osher ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fasting Blood Glucose ◽  
Serum Triglyceride ◽  
Tolerance Test ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Wild Type ◽  
Diet Induced Obesity ◽  
Increased Risk

Background Sex hormone-binding globulin (SHBG) is the main transporter of sex hormones in most vertebrates. Low SHBG levels have been linked to increased risk for diabetes and metabolic syndrome. Polymorphisms of the SHBG gene linked to low SHBG protein levels also strongly predicted increased risk of type 2 diabetes, thus raising the possibility that SHBG may play a role in the pathogenesis of insulin resistance and diabetes. Aim To examine whether expression of human SHBG in mice may ameliorate the development of diabetes and metabolic syndrome in response to a high-fat diet (HFD). Methods Transgene mice expressing a human SHBG transgene (SHBG+) (N = 10/11; males/females) and their wild type littermates (N = 12/8; males/females) were fed HFD for 4.5 months. Results HFD induced comparable obesity in control and SHBG+ mice. Male transgenes had higher muscle mass after 2–3.5 months HFD (0.43 ± 0.028 (n = 4) vs 0.38 ± 0.053 g (n = 7), P = 0.05). Fasting blood glucose, as well as insulin or HOMA-IR, was not different in transgenic vs wild-type males after 4–5 months HFD. Female transgenes had higher fasting glucose (152 ± 29 (n = 7) vs 115 ± 27 mg/dL, P = 0.01 (n = 8)), but mean insulin and HOMA-IR were not different. Likewise, insulin tolerance test and intra-peritoneal glucose tolerance test (GTT) were not different. Finally, SHBG+ mice were not different from controls in terms of liver enzymes, serum triglyceride levels and blood pressure. Conclusion In mice with diet-induced obesity, human SHBG did not protect against development of obesity or dysglycemia.

Triglyceride levels and risk of type 2 diabetes mellitus: a longitudinal large study

2016 ◽  
Vol 64 (2) ◽  
pp. 383-387 ◽  
Author(s):  
Amani Beshara ◽  
Eytan Cohen ◽  
Elad Goldberg ◽  
Pearl Lilos ◽  
Moshe Garty ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Impaired Fasting Glucose ◽  
Triglyceride Level ◽  
Fasting Glucose ◽  
Fasting Blood Glucose ◽  
Serum Triglyceride ◽  
Stepwise Logistic Regression ◽  
Serum Triglyceride Level ◽  
Normal Range ◽  
Wide Range

The relationship between triglyceridemia and diabetes mellitus remains unclear. This study evaluated the risk of diabetes and impaired fasting glucose associated with a wide range of triglyceride levels. A longitudinal retrospective study was carried out employing data from a screening center between the years 2000 and 2012. Inclusion criteria were absence of diabetes at baseline and attendance at the center at least twice over a 5-year period. Participants were divided by fasting blood glucose level (normal/impaired) at the first visit. A total of 5085 participants were eligible for the study. Of the 4164 normoglycemic participants at baseline, 40 (0.96%) had diabetes and 998 (24%) had impaired fasting glucose by the end of the study. On stepwise logistic regression analysis, every 10 mg/dL increase in triglyceride level significantly increased the risk of diabetes by 4% and of impaired fasting glucose by 2% (p<0.001). This association held true even when rising triglyceride levels remained within the accepted normal range (<150 mg/dL, p<0.001). Sustained increments in serum triglyceride level, even within the accepted normal range, are an independent risk factor for diabetes mellitus and impaired fasting glucose in normoglycemic participants.

scholarly journals Cerebrospinal fluid ceftazidime kinetics in patients with external ventriculostomies.

1996 ◽  
Vol 40 (3) ◽  
pp. 763-766 ◽  
Author(s):  
R Nau ◽  
H W Prange ◽  
M Kinzig ◽  
A Frank ◽  
A Dressel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
High Performance ◽  
Elimination Half ◽  
Daily Dose ◽  
Order Of Magnitude ◽  
The Central Nervous System ◽  
Occlusive Hydrocephalus ◽  
A Minor

Ceftazidime has proven to be effective for the treatment of bacterial meningitis caused by multiresistant gram-negative bacteria. Since nosocomial central nervous system infections are often accompanied by only a minor dysfunction of the blood-cerebrospinal fluid (CSF) barrier, patients with noninflammatory occlusive hydrocephalus who had undergone external ventriculostomy were studied (n = 8). Serum and CSF were drawn repeatedly after the administration of the first dose of ceftazidime (3 g over 30 min intravenously), and concentrations were determined by high-performance liquid chromatography by using UV detection. The concentrations of ceftazidime in CSF were maximal at 1 to 13 h (median, 5.5 h) after the end of the infusion and ranged from 0.73 to 2.80 mg/liter (median, 1.56 mg/liter). The elimination half-lives were 3.13 to 18.1 h (median, 10.7 h) in CSF compared with 2.02 to 5.24 h (median, 3.74 h) in serum. The ratios of the areas under the concentration-time curves in CSF and serum (AUCCSF/AUCS) ranged from 0.027 to 0.123 (median, 0.054). After the administration of a single dose of 3 g, the maximum concentrations of ceftazidime in CSF were approximately four times higher than those after the administration of 2-g intravenous doses of cefotaxime (median, 0.44 mg/liter) and ceftriaxone (median, 0.43 mg/liter) (R. Nau, H. W. Prange, P. Muth, G. Mahr, S. Menck, H. Kolenda, and F. Sörgel, Antimicrob. Agents Chemother. 37:1518-1524, 1993). The median AUCCSF/AUCS ratio of ceftazidime was slightly below that of cefotaxime (0.12), but it was 1 order of magnitude above the median AUCCSF/AUCS of ceftriaxone (0.007) (Nau et al., Antimicrob. Agents Chemother. 37:1518-1524, 1993). The concentrations of ceftazidime observed in CSF were above the MICs for most Pseudomonas aeruginosa strains. However, they are probably not high enough to be rapidly bactericidal. For this reason, the daily dose should be increased to 12 g in cases of P. aeruginosa infections of the central nervous system when the blood-CSF barrier is minimally impaired.

Sign in / Sign up

Export Citation Format

Share Document