scholarly journals A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults

2002 ◽  
pp. 49-57 ◽  
Author(s):  
B Ekman ◽  
T Lindstrom ◽  
F Nystrom ◽  
AG Olsson ◽  
G Toss ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Fasting Blood Glucose ◽  
Dose Titration ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Fasting Insulin ◽  
Control Subjects ◽  
Normal Plasma ◽  
Igf I

OBJECTIVE: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I. DESIGN AND METHODS: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects. RESULTS: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study. CONCLUSIONS: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.

scholarly journals FOXN3 hyperglycemic risk allele and insulin sensitivity in humans

2019 ◽  
Vol 7 (1) ◽  
pp. e000688 ◽  
Author(s):  
Melissa L Erickson ◽  
Santhosh Karanth ◽  
Eric Ravussin ◽  
Amnon Schlegel
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Allele Frequency ◽  
Risk Allele ◽  
Fasting Blood Glucose ◽  
Fat Free Mass ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Allele Carrier ◽  
Euglycemic Hyperinsulinemic Clamp

ObjectiveThe rs8004664 variation within the FOXN3 gene is significantly and independently associated with fasting blood glucose in humans. We have previously shown that the hyperglycemia risk allele (A) increases FOXN3 expression in primary human hepatocytes; over-expression of human FOXN3 in zebrafish liver increases fasting blood glucose; and heterozygous deletion of the zebrafish orthologfoxn3decreases fasting blood glucose. Paralleling these model organism findings, we found that rs8004664 A|A homozygotes had blunted glucagon suppression during an oral glucose tolerance test. Here, we test associations between insulin sensitivity and the rs8004664 variation.Research design and methods92 participants (49±13 years, body mass index: 32±6 kg/m2, 28 with and 64 without type 2 diabetes mellitus) were genotyped at rs8004664. Insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp technique.ResultsThe “A” allele frequency was 59%; the protective (G) allele frequency was 41% (A|A: n=29; G|G: n=12; A|G: n=50). Clamp-measured glucose disposal rate (GDR) was not different by genotype (F=0.046, p=0.96) or by “A” allele carrier (p=0.36). Female G|G homozygotes had better insulin sensitivity compared to female “A” allele carriers (GDR; G|G: 9.9±3.0 vs A|A+A|G: 7.1±3.0 mg/kg fat-free mass+17.7/min; p=0.04). Insulin sensitivity was not different by genotype or by “A” allele carriers.ConclusionThe rs8004664 variation within the FOXN3 gene may modulate insulin sensitivity in women.

scholarly journals Ghrelin test for the assessment of GH status in successfully treated patients with acromegaly

2006 ◽  
Vol 154 (5) ◽  
pp. 659-666 ◽  
Author(s):  
S Pekic ◽  
M Doknic ◽  
D Miljic ◽  
M Joksimovic ◽  
J Glodic ◽  
...  
Keyword(s):  
Gh Deficiency ◽  
Provocation Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Provocative Test ◽  
Gh Secretion ◽  
Control Subjects ◽  
Igf I ◽  
Secretory Capacity ◽  
Igfbp 3

Objective: Posttreatment assessment of disease activity and definition of cure of acromegaly, using measurement of GH secretion, remains problematic. Furthermore, with our efforts to achieve tight biochemical control of the disease it is foreseeable that a proportion of patients may be rendered GH deficient, thus requiring testing for GH deficiency. The aim of our study was to evaluate residual GH secretion in cured patients with acromegaly. Design and methods: At baseline, circulating GH, IGF-I, IGFBP-3, leptin and lipid (cholesterol and tri-glycerides) levels were measured in 33 acromegalic patients nine years after treatment with surgery of whom 6 were additionally irradiated. Two tests were performed: the GH suppression test - oral glucose tolerance test (OGTT) and the GH provocation test - ghrelin test (1 μg/kg i.v. bolus) and the results were compared with 11 age- and sex-matched control subjects. Results: According to the consensus criteria (normal IGF-I levels and post-OGTT GH nadir <1 μg/l), 21 treated acromegalic patients were cured, 6 had discordant IGF-I and GH nadir values during OGTT, while 6 had persistent acromegaly. After the GH provocative test with ghrelin (cut-off for severe GH deficiency is GH <3 μg/l), we detected 9 severely GH deficient patients (GHD) among 21 cured acromegalic patients. Mean GH peak (±s.e.m.) response to the ghrelin test in GHD acromegalics was significantly lower compared with acromegalics with sufficient GH secretory capacity and control subjects (1.2 ± 0.2 μg/l vs 20.1 ± 2.4 μg/l vs 31.1 ± 2.5 μg/l respectively, P<0.0001). Mean IGF-I and IGFBP-3 levels were not different between GHD and GH-sufficient cured acromegalics. Leptin levels and body mass index (BMI) were significantly higher in GHD male acromegalics compared with GH-sufficient male acromegalics. GHD female acromegalics tended to have higher BMIs while leptin levels were not different. Conclusions: The assessment of residual GH secretory capacity by the GH provocation test is necessary in the long-term follow-up of successfully treated acromegalics since a large proportion of these patients are rendered GH deficient.

scholarly journals GESTATIONAL DIABETES MELLITUS

2012 ◽  
Vol 19 (04) ◽  
pp. 462-468
Author(s):  
M. IKRAM ◽  
SYED HAIDER HASAN ALAM ◽  
SHAFQAT MUKHTAR ◽  
M. Saeed
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Gestational Diabetes Mellitus ◽  
Glucose Tolerance Test ◽  
Fasting Blood Glucose ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance

Introduction: Gestational diabetes mellitus is common disorder in pregnancy. It is associated with adverse pregnancy outcome. There is no consensus regarding the optimal approach to screening of gestational diabetes mellitus. The present study has tried toobserve the value of fasting blood glucose in screening of gestational diabetes. Objective: To determine the frequency of patients in whomfasting blood glucose and 100gm glucose tolerance show agreement for screening of gestational diabetes mellitus at 24 -28 wks. Studydesign: Comparative cross sectional study. Settings: The study was conducted at Gynecology and Obstetrics department Shaikh ZayedFederal Post Graduate Institute Lahore. Duration of study with dates: 6 months from 12Nov 2010 to 11 May 2011. Material and method: Thestudy included 135 booked patients with positive family history of diabetes mellitus. All patients underwent fasting blood glucose at 24-28 weeksof gestation, regardless of results of fasting blood glucose on next visit they underwent 100g oral glucose tolerance test (OGTT). The agreementbetween fasting blood glucose and 100g oral glucose tolerance test was calculated in frequency and percentages. Results: The mean age ofwomen in studied population was 27.15±3.70.Out of 135 patients 86.7 %( 117) showed agreement between results of fasting blood glucose and100g OGTT while 13.31 %( 18) showed no agreement between both of the tests. Conclusions: Fasting blood glucose is a good screeningoption for gestational diabetes mellitus along with positive history. It provides a simple, cheap and more practical test for screening of gestationaldiabetes mellitus. However diagnostic confirmation with 100g OGTT should be done.

scholarly journals An evolving spectrum of diabetes in a woman with GCK-MODY

2019 ◽  
Vol 2019 ◽  
Author(s):  
Aoife Garrahy ◽  
Matilde Bettina Mijares Zamuner ◽  
Maria M Byrne
Keyword(s):  
Blood Glucose ◽  
Fasting Glucose ◽  
Autoimmune Diabetes ◽  
Post Partum ◽  
Fasting Blood Glucose ◽  
Oral Glucose ◽  
List Type ◽  
Latent Autoimmune Diabetes ◽  
Frequent Episodes ◽  
First Case

Summary Coexistence of autoimmune diabetes and maturity-onset diabetes of the young (MODY) is rare. We report the first case of coexisting latent autoimmune diabetes of adulthood (LADA) and glucokinase (GCK) MODY. A 32-year-old woman was treated with insulin for gestational diabetes at age 32 years; post-partum, her fasting blood glucose was 6.0 mmol/L and 2-h glucose was 11.8 mmol/L following an oral glucose tolerance test, and she was maintained on diet alone. Five years later, a diagnosis of LADA was made when she presented with fasting blood glucose of 20.3 mmol/L and HbA1C 125 mmol/mol (13.6%). GCK-MODY was identified 14 years later when genetic testing was prompted by identification of a mutation in her cousin. Despite multiple daily insulin injections her glycaemic control remained above target and her clinical course has been complicated by multiple episodes of hypoglycaemia with unawareness. Although rare, coexistence of latent autoimmune diabetes of adulthood and monogenic diabetes should be considered if there is a strong clinical suspicion, for example, family history. Hypoglycaemic unawareness developed secondary to frequent episodes of hypoglycaemia using standard glycaemic targets for LADA. This case highlights the importance of setting fasting glucose targets within the expected range for GCK-MODY in subjects with coexisting LADA. Learning points: We report the first case of coexisting latent autoimmune diabetes of adulthood (LADA) and GCK-MODY. It has been suggested that mutations in GCK may lead to altered counter-regulation and recognition of hypoglycaemia at higher blood glucose levels than patients without such mutation. However, in our case, hypoglycaemic unawareness developed secondary to frequent episodes of hypoglycaemia using standard glycaemic targets for LADA. This case highlights the importance of setting fasting glucose targets within the expected range for GCK-MODY in subjects with coexisting LADA to avoid hypoglycaemia.

scholarly journals Contributions of Prenatal Exposures and Child Lifestyle to Insulin Sensitivity

2020 ◽  
Vol 105 (7) ◽  
pp. 2413-2421
Author(s):  
Jasmin M Alves ◽  
Jennifer Zink ◽  
Ting Chow ◽  
Shan Luo ◽  
Britni R Belcher ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Sensitivity ◽  
Vigorous Physical Activity ◽  
Lifestyle Factors ◽  
Total Sugar ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Prenatal Exposures ◽  
Added Sugar ◽  
Prepregnancy Bmi

Abstract Context Prenatal exposures and lifestyle factors are important for metabolic health. Objective Determine how prenatal exposures to maternal obesity and/or gestational diabetes mellitus (GDM) and childhood lifestyle factors independently contribute to child insulin sensitivity. Design and Participants Ninety children aged 7 to 11 years (56% girls, 60% exposed to GDM), born at Kaiser-Permanente Southern California, completed an oral glucose tolerance test (OGTT) as part of the BrainChild Study. Matsuda insulin sensitivity index (ISI) was used to estimate insulin sensitivity. Participants completed two 24-hour dietary recalls, and daily energy intake (EI), dietary added sugar, and total sugar were calculated. The 3-day physical activity recall determined the average minutes per day of moderate to vigorous physical activity (MVPA) and the average minutes per day spent sedentary. Maternal prepregnancy body mass index (BMI) and GDM status were extracted from electronic medical records. Main Outcome Measure Matsuda-ISI. Results Linear regression showed that children who spent more time in MVPA had better ISI (β = 0.33; P = 0.001), and results remained after adjustment for maternal prepregnancy BMI, GDM exposure, child age, sex, daily EI, dietary added sugar (β = 0.34; P = 0.001), and further adjustment for child adiposity (β = 0.29; P = 0.001). Time spent sedentary, maternal prepregnancy BMI, GDM exposure, dietary added sugar, total sugar, and EI were not associated with ISI. Conclusions Physical activity was the only predictor of ISI at this age, suggesting that engaging in physical activity during childhood is beneficial for insulin sensitivity and may ameliorate future risk for metabolic disease.

scholarly journals Elevated Circulating Fetuin-B Levels Are Associated with Insulin Resistance and Reduced by GLP-1RA in Newly Diagnosed PCOS Women

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Mani Mokou ◽  
Shan Yang ◽  
Bin Zhan ◽  
Shan Geng ◽  
Kejia Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Metabolic Diseases ◽  
Polycystic Ovary ◽  
Fasting Blood Glucose ◽  
Resistance Index ◽  
Oral Glucose ◽  
Healthy Women ◽  
Tnf Α

Background. Previous studies have suggested that Fetuin-B seems to be a secreted adipokine related to metabolic diseases. However, the results have been inconsistent. Here, our objective is to investigate the changes in circulating Fetuin-B levels in women with polycystic ovary syndrome (PCOS) and analyze the association of Fetuin-B and insulin resistance (IR). Methods. The current study is comprised of a cross-sectional study and a series of interventional studies. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp (EHC) were engaged to assess glucose tolerance and insulin sensitivity. Serum Fetuin-B levels were determined by ELISA. Results. Serum Fetuin-B and TNF-α levels were markedly increased in women with PCOS compared to healthy women. Circulating Fetuin-B was positively associated with body mass index, waist-to-hip ratio, the percentage of body fat (FAT%), systolic blood pressure, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, 2 h blood glucose after glucose overload, fasting insulin, 2 h insulin after glucose overload, HOMA-insulin resistance index (HOMA-IR), the area under the curve for insulin (AUCi), AUCg, and TNF-α, while negatively associated with M value and follicular stimulating hormone (FSH). During the EHC, Fetuin-B levels were found to be significantly increased in PCOS women. After a glucose challenge, serum Fetuin-B levels in healthy women were significantly increased. Lipid infusion reduced serum Fetuin-B levels in 30 healthy subjects. After six months of glucagon-like peptide-1 receptor agonist (GLP-1RA) intervention, serum Fetuin-B concentrations in PCOS women markedly decreased following ameliorated IR. Conclusion. Our results indicate that Fetuin-B may be a biomarker of IR in individuals with PCOS. This trial is registered with ChiCTR-IIR-16007901.

scholarly journals The Role of Untimed Blood Glucose in Screening for Gestational Diabetes Mellitus in a High Prevalent Diabetic Population

Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Sarah Cuschieri ◽  
Johann Craus ◽  
Charles Savona-Ventura
Keyword(s):  
Blood Glucose ◽  
Gestational Diabetes ◽  
Pregnant Women ◽  
Fasting Blood Glucose ◽  
Diabetes Type 2 ◽  
Obstetric Outcomes ◽  
Oral Glucose ◽  
Stepwise Logistic Regression ◽  
Operating Characteristics ◽  
Screening Protocol

Global prevalence increase of diabetes type 2 and gestational diabetes (GDM) has led to increased awareness and screening of pregnant women for GDM. Ideally screening for GDM should be done by an oral glucose tolerance test (oGTT), which is laborious and time consuming. A randomized glucose test incorporated with anthropomorphic characteristics may be an appropriate cost-effective combined clinical and biochemical screening protocol for clinical practice as well as cutting down on oGTTs. A retrospective observational study was performed on a randomized sample of pregnant women who required an OGTT during their pregnancy. Biochemical and anthropomorphic data along with obstetric outcomes were statistically analyzed. Backward stepwise logistic regression and receiver operating characteristics curves were used to obtain a suitable predictor for GDM without an oGTT and formulate a screening protocol. Significant GDM predictive variables were fasting blood glucose (p=0.0001) and random blood glucose (p=0.012). Different RBG and FBG cutoff points with anthropomorphic characteristics were compared to carbohydrate metabolic status to diagnose GDM without oGTT, leading to a screening protocol. A screening protocol incorporating IADPSG diagnostic criteria, BMI, and different RBG and FBG criteria would help predict GDM among high-risk populations earlier and reduce the need for oGTT test.

Body mass index and ovarian function are associated with endocrine and metabolic abnormalities in women with hyperandrogenic syndrome

2008 ◽  
Vol 158 (5) ◽  
pp. 711-719 ◽  
Author(s):  
S Cupisti ◽  
N Kajaia ◽  
R Dittrich ◽  
H Duezenli ◽  
M W Beckmann ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Density Lipoprotein ◽  
Sex Hormone Binding Globulin ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Metabolic Abnormalities ◽  
Insulin Levels ◽  
Homeostatic Model

BackgroundThe aim of this study was to evaluate associations of clinical features, such as hirsutism, polycystic ovaries (PCOs), ovulatory dysfunction, and body mass index (BMI) ≥25 kg/m2, with metabolic abnormalities in hyperandrogenic women.MethodsHirsutism was based on the modified Ferriman–Gallwey score. Ovulatory function was classified as eumenorrhea, oligomenorrhea and amenorrhea, and PCOs were assessed using the ultrasound criteria recommended in the Rotterdam definition. An oral glucose tolerance test was performed. Different insulin resistance (IR) indices were calculated.ResultsHirsute women had significantly higher BMI, DHEA sulfate (DHEAS) and free androgen index (FAI), and significantly lower values for sex hormone-binding globulin (SHBG). Women with amenorrhea were younger in comparison to women with eumenorrhea and had significantly higher values for fasting insulin (FI) and 1- and 2-h insulin levels; lower values for glucose to insulin ratio (GIR), quantitative insulin sensitivity check index (QUICKI), and SHBG. Women with PCO had significantly higher levels of LH and low-density lipoprotein (LDL), whereas high-density lipoprotein (HDL) levels were significantly lower. Women with a BMI ≥25 kg/m2 had significantly higher values for age, fasting plasma glucose, FI, and 1- and 2-h glucose and insulin levels, homeostatic model for assessment of IR (HOMA-IR), homeostatic model for assessment of B-cell function (HOMA-B), and FAI, whereas their GIR, insulin sensitivity index, QUICKI, SHBG, and HDL were significantly lower.ConclusionsIn women with hyperandrogenic syndrome, BMI≥25 kg/m2 and amenorrhea appear to be associated with severe endocrine and metabolic abnormalities.

TIMING OF ACUTE PASSIVE HEATING ON GLUCOSE TOLERANCE AND BLOOD PRESSURE IN PEOPLE WITH TYPE 2 DIABETES: A RANDOMIZED, BALANCED CROSSOVER, CONTROL TRIAL

2021 ◽  
Author(s):  
Thomas Joseph James ◽  
Jo Corbett ◽  
Michael H. Cummings ◽  
Sharon Allard ◽  
John S. Young ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Microvascular Dysfunction ◽  
Oral Glucose ◽  
Passive Heating ◽  
Chronic Hyperglycemia

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia and progressive insulin resistance, leading to macro and microvascular dysfunction. Passive heating has potential to improve glucose homeostasis and act as an exercise mimetic. We assessed the effect of acute passive heating before or during an oral glucose tolerance test (OGTT) in people with T2DM. Twelve people with T2DM were randomly assigned to 3 conditions:1) 3 h OGTT (CON); 2) 1 h passive heating (40 °C water) 30 min before an OGTT (HOT-OGTT); and 3) 1 h passive heating (40 °C water) 30 min after commencing an OGTT (OGTT-HOT). Blood [glucose], insulin sensitivity, extracellular heat shock protein 70 (eHSP70), total energy expenditure (TEE), heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) were recorded. Passive heating did not alter blood [glucose] (CON, 1,677 (386) a.u.; HOT-OGTT, 1,797 (340) a.u.; OGTT-HOT, 1,662 (364) a.u.; P = 0.28), insulin sensitivity (P = 0.15), or SBP (P = 0.18), but did increase [eHSP70] in both heating conditions (CON, 203.48 (110.81) pg·mL-1; HOT-OGTT, 402.47 (79.02) pg·mL-1; OGTT-HOT, 310.00 (60.53) pg·mL-1; P < 0.001), increased TEE (via fat oxidation) in the OGTT-HOT condition (CON, 263 (33) kcal; HOT-OGTT, 278 (40) kcal; OGTT-HOT, 304 (38) kcal; P = 0.001), increased HR in both heating conditions (P < 0.001) and reduced DBP in OGTT-HOT condition (P < 0.01). Passive heating in close proximity to a glucose challenge does not alter glucose tolerance but does increase [eHSP70] and TEE, and reduce blood pressure in people with T2DM.

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