One-year postpartum weight retention and glucose intolerance in women with prediabetes after gestational diabetes.

AIMS: To determine risk factors for 1-year postpartum weight retention (PPWR) and glucose intolerance (prediabetes + diabetes) in women with a previous history of gestational diabetes (GDM) and prediabetes in early postpartum. METHODS: In this exploratory analysis of the MELINDA randomized controlled trial, we report data of 167 women with prediabetes at the 6-16 weeks (early) postpartum oral glucose tolerance test after a recent history of GDM. RESULTS: Of all participants, 45% (75) had PPWR >0 kg at 1-year postpartum. Compared to women without PPWR, women with PPWR had higher gestational weight gain [10.5 ± 6.4 vs. 6.5 ± 4.5 kg, p < 0.001], higher BMI (p < 0.01) and a worse metabolic profile (higher waist circumference, worse lipid profile and more insulin resistance) (all p < 0.05) both in early and late postpartum. Of all women with PPWR, 40.0% developed metabolic syndrome, compared to 18.9% of women without late PPWR (p = 0.003). The only independent predictor for late PPWR was weight retention in early postpartum (p < 0.001). Of all participants, 55.1% (92) had glucose intolerance (84 prediabetes, 8 diabetes) 1-year postpartum. Independent predictors for late postpartum glucose intolerance were lower gestational age at start insulin therapy in pregnancy and delivery by caesarean section (resp. p = 0.044 and 0.014). CONCLUSIONS: In women with a previous history of GDM and prediabetes in early postpartum, PPWR in early postpartum was a strong independent predictor for late PPWR, while earlier start of insulin therapy during pregnancy and delivery by caesarean section were independent predictors of glucose intolerance in late postpartum.

Impact of breastfeeding on risk of glucose intolerance in early postpartum after gestational diabetes.

Aims: To determine the impact of breastfeeding on the risk of postpartum glucose intolerance in women with gestational diabetes. Methods: Sub-analysis of two multi-centric prospective cohort studies (BEDIP-N and MELINDA) in 1008 women with gestational diabetes. Data were collected during pregnancy and at a mean of 12 weeks postpartum. Multivariate logistic regression was used to estimate the effect of breastfeeding on glucose intolerance, with adjustment for ethnicity, education, income, professional activity and BMI. Results: Of all participants, 56.3% (567) breastfed exclusively, 10.1% (102) gave mixed milk feeding and 33.6% (339) did not breastfeed. Mean breastfeeding duration was 3.8 ± 2.4 and 3.7 ± 2.1 months in the breastfeeding and mixed milk feeding groups (p=0.496). The rate of glucose intolerance was lower in both the breastfeeding [22.3% (126)] and mixed milk feeding [25.5% (26)] groups compared to the no breastfeeding group [29.5% (100)], with an adjusted OR of 0.7 (95% CI 0.5-1.0) for glucose intolerance in the breastfeeding group compared to no breastfeeding group and an adjusted OR of 0.7 (95% CI 0.4-1.2) for the mixed milk feeding group compared to the no breastfeeding group. Postpartum, breastfeeding women had a lower BMI, less often postpartum weight retention, lower fasting triglycerides, less insulin resistance and a higher insulin secretion-sensitivity index-2 than the mixed milk feeding and no breastfeeding group. The mixed milk feeding group was more often from an non-White background, had a lower blood pressure and lower fasting triglycerides compared to the no breastfeeding group. Conclusions: Breastfeeding (exclusive and mixed milk feeding) is associated with less glucose intolerance and a better metabolic profile in early postpartum in women with gestational diabetes.

Effectiveness of a blended mobile-based lifestyle intervention in women with glucose intolerance after a recent history of gestational diabetes (MELINDA): a 1-year, prospective, multicentre, randomised controlled trial.

Background: Women with glucose intolerance after gestational diabetes mellitus (GDM) are at high risk to develop type 2 diabetes. Traditional lifestyle interventions in early postpartum have limited impact. We investigated the efficacy of a blended mobile-based lifestyle intervention in women with glucose intolerance after a recent history of GDM. Methods: Prospective, double-arm, non-masked, multicentre randomised controlled trial (RCT) in which women with glucose intolerance, diagnosed 6-16 weeks after a GDM-complicated pregnancy, were assigned 1:1 to a one-year blended-care, telephone- and mobile-based lifestyle program (intervention) or usual care (control). Primary endpoint was the proportion of women able to achieve their weight goal (≥5% weight loss if prepregnancy BMI ≥ 25 kg/m2 or return to prepregnancy weight if prepregnancy BMI < 25 kg/m2) in the intention-to-treat sample. Key secondary outcomes were frequency of glucose intolerance, diabetes and metabolic syndrome, and lifestyle-related outcomes assessed with self-administered questionnaires. The study was registered in ClinicalTrials.gov (NCT03559621). Findings: Between April 10th 2019 and May 13th 2022, 240 participants were assigned to the intervention (n = 121) or control group (n = 119), of which 167 (n = 82 in intervention and n = 85 in control group) completed the study. Primary outcome was achieved by 46.3% (56) of intervention participants compared to 43.3% (52) in the control group [odds ratio (OR) 1.13, 95% confidence interval (CI) 0.63-2.03, p = 0.680; risk ratio 1.07, 95% CI (0.78-1.48)]. Women in the intervention group developed significantly less often metabolic syndrome compared to the control group [7.3% (6) vs. 16.5% (14), OR 0.40, CI (0.22-0.72), p = 0.002], reported less sedentary behaviour and higher motivation for continuing healthy behaviours. In the intervention group, 84.1% (69) attended at least eight telephone sessions and 70.7% (58) used the app at least once weekly. Interpretation: A blended, mobile-based lifestyle intervention was not effective in achieving weight goals, but reduced the risk to develop metabolic syndrome. Funding: Research fund of University Hospitals Leuven, Novo Nordisk, Sanofi, AstraZeneca, Boehringer-Ingelheim, Lilly.

Beta-HCG Secretion by a Pulmonary Choriocarcinoma in a Male Patient.

Background: Paraneoplastic secretion of beta-subunit of human chorionic gonadotropin (ß-HCG) in pulmonary carcinoma is rare. Case Presentation. A 65-year-old man presented with bilateral gynaecomastia with abnormally high levels of ß-hCG and elevated oestradiol, progesterone, and testosterone levels on April 7, 2023. After excluding testicular malignancy, CT scan of the chest and abdomen revealed bilateral pulmonary lesions. Transthoracic biopsy confirmed malignancy with choriocarcinoma. MRI of the brain showed a solitary brain metastasis, while on a subsequent 18F-FDG PET/CT, no other metastatic lesions were seen. The patient was treated with chemoimmunotherapy carboplatin-etoposide-pembrolizumab with good partial response. Conclusion: Our case of a presumably stage IV dedifferentiated mNSCLC presenting as an extragonadal ß-hCG secreting pulmonary choriocarcinoma is a very rare tumor with a poor prognosis. Its biology, origin, and treatment remain to be elucidated. Cancer genome sequencing is necessary for the identification of the origin and seeking treatment.

Weight retention and glucose intolerance in early postpartum after gestational diabetes.

OBJECTIVES: To determine risk factors for early postpartum weight retention (PPWR) and glucose intolerance (GI) in women with gestational diabetes (GDM). DESIGN & METHODS: Prospective, multicenter (n=8) cohort study in 1201 women with a recent history of GDM. Pregnancy and postpartum characteristics, and data from self-administered questionnaires were collected at the 6-16 weeks postpartum 75g OGTT. RESULTS: Of all participants, 38.6% (463) had moderate (>0 and ≤5 kg) and 15.6% (187) had high (>5kg) PPWR. Independent predictors for early PPWR were excessive gestational weight gain (GWG), lack of breastfeeding, higher dietary fat intake, insulin use during pregnancy, multiparity, lower prepregnancy BMI, and lower education degree. Compared to PPWR <5 kg, women with high PPWR had a more impaired postpartum metabolic profile, breastfed less often, had higher depression rates [23.1% (43) vs. 16.0% (74), p=0.035] and anxiety levels, and lower quality of life. Of all participants, 28.0% (336) had GI [26.1% (313) prediabetes and 1.9% (23) diabetes]. Women with high PPWR had more often GI compared to women without PPWR [33.7% (63) vs. 24.9% (137), p=0.020]. Only 12.9% (24) of women with high PPWR perceived themselves at high risk for diabetes but they were more often willing to change their lifestyle than women with moderate PPWR. CONCLUSIONS: Modifiable risk factors such as lifestyle, prepregnancy BMI, GWG, and mental health can be used to identify a subgroup of women with GDM at the highest risk of developing early PPWR, allowing for a more personalized follow-up.

False positive Herpes Simplex IgM serology in COVID-19 patients correlates with SARS-CoV-2 IgM/IgG seropositivity.

Differentiating COVID-19 from other causes of viral pneumonia, like herpes simplex (HSV), can be complicated by shared clinical and laboratory features. Viral pneumonia is mostly diagnosed based on molecular or serological techniques. Serological immunoassay interferences, often attributed to concurrent appearance of heterologous (viral) immunoglobulins, is well-known, but has not been studied in COVID-19 patients. Following false positive HSV immunoglobulin M (IgM) results in our index patient, 25 other COVID-19 patients were tested for HSV-1/2 IgM with the chemiluminescent Liaison assay and Euroimmun enzyme-linked immunosorbent assay. Forty-five percent of COVID-19 patients tested positive for HSV IgM with Liaison. No HSV indices were positive with Euroimmun enzyme-linked immunosorbent assay, suggesting immunoassay interference. Significant correlation between HSV IgM and SARS-CoV-2 IgM/IgG positivity was found. Adding 0.5% polyvinylpyrrolidone, inhibiting non-specific solid-phase adsorption, abolished interference in 22% of false positive cases, suggesting interference caused by solid-phase reactive IgM. Hence, serologic immunoassay results should be interpreted with caution in COVID-19 patients.

Corticotroph pituitary carcinoma with skeletal metastases masquerading as ectopic ACTH syndrome: a long and winding road to diagnosis.

Summary: Pituitary carcinoma is a rare type of malignancy and only accounts for 0.1-0.2% of all pituitary tumours. Most pituitary carcinomas are hormonally active and they are mostly represented by corticotroph and lactotroph carcinomas. Corticotroph carcinoma can present as symptomatic Cushing's disease or can evolve from silent corticotroph adenoma which is not associated with clinical or biochemical evidence of hypercortisolism. We hereby present a case of a bone-metastasized corticotroph pituitary carcinoma masquerading as an ectopic adrenocorticotropic hormone (ACTH) syndrome in a patient with a history of a non-functioning pituitary macro-adenoma. Our patient underwent two transsphenoidal resections of the primary pituitary tumour followed by external beam radiation therapy. Under hydrocortisone substitution therapy she developed ACTH-dependent hypercortisolism without arguments for recurrence on pituitary MRI and without central-to-peripheral ACTH-gradient on inferior petrosal sinus sampling, both suggesting ectopic production. Ultimately, she was diagnosed with an ACTH-secreting vertebral metastasis originating from the primary pituitary tumour. This case report demonstrates the complex pathophysiology of pituitary carcinoma and the long diagnostic work-up. Certain features in pituitary adenoma should raise the suspicion of malignancy. Learning points: The diagnosis of pituitary carcinoma can only be made based on documented metastasis, therefore, due to the often long latency period between the detection of the primary tumour and the occurrence of metastasis, the diagnostic work-up most often spans over multiple years. Pituitary carcinoma including corticotroph carcinoma is very rare in contrast to pituitary adenoma and only accounts for 0.1-0.2% of all pituitary tumours. Histopathology in pituitary adenoma should certainly accomplish the following goals: accurate tumour subtyping and assessment of tumoural proliferative potential. Repeated recurrence of pituitary adenoma after surgical resection, a discrepancy between biochemical and radiological findings, resistance to medical and radiation therapy, and silent tumours becoming functional are all hallmarks of pituitary carcinoma. Silent corticotroph adenomas are non-functioning pituitary adenomas that arise from T-PIT lineage adenohypophyseal cells and that can express adrenocorticotropic hormone on immunohistochemistry, but are not associated with biochemical or clinical evidence of hypercortisolism. Silent corticotroph adenomas exhibit a more aggressive clinical behaviour than other non-functioning adenomas. Treatment options for corticotroph carcinoma include primary tumour resection, radiation therapy, medical therapy, and chemotherapy. Sometimes bilateral adrenalectomy is necessary to achieve sufficient control of the cortisol excess.

Mobile-Based Lifestyle Intervention in Women with Glucose Intolerance after Gestational Diabetes Mellitus (MELINDA), A Multicenter Randomized Controlled Trial: Methodology and Design.

The aims of the 'Mobile-based lifestyle intervention in women with glucose intolerance after gestational diabetes mellitus (GDM)' study (MELINDA) are: (1) to evaluate the prevalence and risk factors of glucose intolerance after a recent history of GDM; and (2) to evaluate the efficacy and feasibility of a telephone- and mobile-based lifestyle intervention in women with glucose intolerance after GDM. This is a Belgian multicenter randomized controlled trial (RCT) in seven hospitals with the aim of recruiting 236 women. Women in the intervention group will receive a blended program, based on one face-to-face education session and further follow-up through a mobile application and monthly telephone advice. Women in the control group will receive follow-up as in normal routine with referral to primary care. Participants will receive an oral glucose tolerance test (OGTT) one year after baseline. Primary endpoint is the frequency of weight goal achievement (≥5% weight loss if pre-pregnancy BMI ≥ 25 Kg/m2 or return to pre-gravid weight if BMI < 25 Kg/m2). At each visit blood samples are collected, anthropometric measurements are obtained, and self-administered questionnaires are completed. Recruitment began in May 2019.

Accelerated Progression to Type 1 Diabetes in the Presence of HLA-A*24 and -B*18 Is Restricted to Multiple Islet Autoantibody-Positive Individuals With Distinct HLA-DQ and Autoantibody Risk Profiles.

OBJECTIVE: We investigated the effect of HLA class I risk alleles on disease progression in various phases of subclinical islet autoimmunity in first-degree relatives of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A registry-based group of siblings/offspring (aged 0-39 years) was monitored from single- to multiple-autoantibody positivity (n = 267) and from multiple-autoantibody positivity to clinical onset (n = 252) according to HLA-DQ, -A*24, -B*18, and -B*39 status. Genetic markers were determined by PCR sequence-specific oligotyping. RESULTS: Unlike HLA-B*18 or -B*39, HLA-A*24 was associated with delayed progression from single- to multiple-autoantibody positivity (P = 0.009) but not to type 1 diabetes. This occurred independently from older age (P < 0.001) and absence of HLA-DQ2/DQ8 or -DQ8 (P < 0.001 and P = 0.003, respectively), and only in the presence of GAD autoantibodies. In contrast, HLA-A*24 was associated with accelerated progression from multiple-autoantibody positivity to clinical onset (P = 0.006), but its effects were restricted to HLA-DQ8+ relatives with IA-2 or zinc transporter 8 autoantibodies (P = 0.002). HLA-B*18, but not -B*39, was also associated with more rapid progression, but only in HLA-DQ2 carriers with double positivity for GAD and insulin autoantibodies (P = 0.004). CONCLUSIONS: HLA-A*24 predisposes to a delayed antigen spreading of humoral autoimmunity, whereas HLA-A*24 and -B*18 are associated with accelerated progression of advanced subclinical autoimmunity in distinct risk groups. The relation of these alleles to the underlying disease process requires further investigation. Their typing should be relevant for the preparation and interpretation of observational and interventional studies in asymptomatic type 1 diabetes.

Correction: Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio.

[This corrects the article DOI: 10.1371/journal.pone.0166702.].

Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio.

BACKGROUND: The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive function tests such as the proinsulin:C-peptide ratio (PI:C). The present study aims to optimize precision of PI:C measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA), and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release. METHODS: Between-day imprecision (n = 20) and split-sample analysis (n = 95) were used to compare TT-TRFIA (AutoDelfia, Perkin-Elmer) with separate methods for proinsulin (in-house TRFIA) and C-peptide (Elecsys, Roche). High-risk multiple autoantibody-positive first-degree relatives (n = 49; age 5-39) were tested for fasting PI:C, HOMA2-IR and hyperglycemic clamp and followed for 20-57 months (interquartile range). RESULTS: TT-TRFIA values for proinsulin, C-peptide and PI:C correlated significantly (r2 = 0.96-0.99; P<0.001) with results obtained with separate methods. TT-TRFIA achieved better between-day %CV for PI:C at three different levels (4.5-7.1 vs 6.7-9.5 for separate methods). In high-risk relatives fasting PI:C was significantly and inversely correlated (rs = -0.596; P<0.001) with first-phase C-peptide release during clamp (also with second phase release, only available for age 12-39 years; n = 31), but only after normalization for HOMA2-IR. In ROC- and Cox regression analysis, HOMA2-IR-corrected PI:C predicted 2-year progression to diabetes equally well as clamp-derived C-peptide release. CONCLUSIONS: The reproducibility of PI:C benefits from the automated simultaneous determination of both hormones. HOMA2-IR-corrected PI:C may serve as a minimally invasive alternative to the more tedious hyperglycemic clamp test.

Active acromegaly is associated with decreased hs-CRP and NT-proBNP serum levels: insights from the Belgian registry of acromegaly.

OBJECTIVE: Patients with active acromegaly have an increased prevalence of cardiomyopathy and heart failure but a less than expected risk of coronary artery disease, considering the frequent association of diabetes mellitus and hypertension. We examined whether changes in high-sensitive C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) might contribute to this phenomenon. DESIGN AND METHODS: Two hundred patients of the Belgian acromegaly registry (AcroBel) were divided in two groups: active disease (IGF1 Z-score >2; n=95) and controlled disease (IGF1 Z-score ≤2; n=105). Serum levels of hs-CRP and NT-proBNP were measured and correlated with BMI, blood pressure, fasting lipids, fasting glucose and insulin, HbA1c, IGF1, interleukin 6 (IL6), adiponectin, and sE-selectin. In a subset of acromegaly patients, hs-CRP, IL6, and NT-proBNP levels were also compared with those/the values of an age-, gender-, and BMI-matched reference group. RESULTS: Patients with active acromegaly had significantly lower levels of hs-CRP (median (interquartile range), 0.5 mg/l (0.1, 0.9) vs 1.3 mg/l (0.5, 4.1); P<0.001) and NT-proBNP, (47.0 ng/l (26.0, 86.0) vs 71.0 ng/l (43.0, 184.0); P<0.001) compared with patients with controlled acromegaly. Compared with the reference population, hs-CRP was not different in controlled acromegaly but significantly lower in active acromegaly (median, 0.4 mg/l (0.1, 0.8) vs 1.4 mg/l (0.8, 2.9); P<0.001), while NT-proBNP was similar in active acromegaly but significantly higher in controlled acromegaly (66.5 ng/l (40.0, 119.5) vs 50.8 ng/l (26.5, 79.7); P<0.001). CONCLUSIONS: Patients with active acromegaly have significantly lower values of NT-proBNP and hs-CRP compared with patients with controlled disease and even lower values of hs-CRP compared with control subjects.

Modification of hormonal secretion in clinically silent pituitary adenomas.

BACKGROUND: Silent pituitary adenomas are a subtype of adenomas characterized by positive immunoreactivity for one or more hormones classically secreted by normal pituitary cells but without clinical expression, although in some occasions enhanced or changed secretory activity can develop over time. Silent corticotroph adenomas are the classical example of this phenomenon. PATIENTS AND METHODS: A series of about 500 pituitary adenomas seen over a period of 20 years were screened for modification in hormonal secretion. Biochemical and immunohistochemical data were reviewed. RESULTS: Two cases were retrieved, one silent somatotroph adenoma and one thyrotroph adenoma, both without specific clinical features or biochemical abnormalities, which presented 20 years after initial surgery with evidence of acromegaly and hyperthyroidism, respectively. While the acromegaly was controlled by a combination of somatostatin analogs and growth hormone (GH) receptor antagonist therapy, neurosurgery was necessary to manage the thyrotroph adenoma. Immunohistochemical examination demonstrated an increase in the number of thyroid stimulating hormone (TSH)-immunoreactive cells compared to the first tissue. Apparently, the mechanisms responsible for the secretory modifications are different, being a change in secretory capacity in the silent somatotroph adenoma and a quantitative change in the silent thyrotroph adenoma. CONCLUSIONS: These two cases, one somatotroph and one thyrotroph adenoma, are an illustration that clinically silent pituitary adenomas may in rare circumstances evolve over time and become active, as previously demonstrated in silent corticotroph adenomas.

GH replacement in hypopituitarism improves lipid profile and quality of life independently of changes in obesity variables.

OBJECTIVE: GH deficiency (GHD) in adults is characterized by elevated body mass index (BMI), increased waist girth (WG) and increased fat mass (FM). Information about how these indicators of obesity affect the lipid profile and quality of life (QoL) of GHD subjects is scarce. It is also unclear how changes in these indicators brought about by GH replacement influence lipids and QoL. DESIGN AND METHODS: Adult GHD subjects from the Pfizer International Metabolic Database were grouped according to BMI (n=291 with BMI <25 kg/m(2), n=372 with BMI 25-30 kg/m(2), n=279 with BMI >30 kg/m(2)), WG (n=508 with normal WG, n=434 with increased WG) and FM (n=357) and according to changes in these variables after 1 year of GH replacement. Serum IGF-I concentrations, lipid concentrations and QoL using the QoL Assessment of GHD in Adults questionnaire were assessed at baseline and after 1 year of treatment. RESULTS: At baseline, total and low-density lipoprotein (LDL) cholesterol were similarly elevated in the BMI and WG groups, but high-density lipoprotein (HDL) cholesterol decreased and triglycerides increased with increasing BMI and WG. QoL was progressively poorer with increasing BMI and WG. After 1 year of GH replacement, total and LDL cholesterol and QoL improved in all BMI, WG and FM groups. CONCLUSIONS: Variables of obesity adversely affect the already unfavourable lipid profile in GHD subjects by decreasing HDL cholesterol, but do not counteract the positive effect of GH replacement on LDL cholesterol. Similarly, QoL is influenced by obesity, but responds equally well to GH treatment independent of BMI, WG and FM.

Remission of acromegaly following long-term therapy with cabergoline: report of two cases.

Dopamine agonists are effective in some patients with acromegaly and in this condition treatment is considered to be chronic. We describe two acromegalic patients who responded adequately to the long-acting dopamine agonist cabergoline, but surprisingly maintained normal GH and IGF-I levels once therapy was discontinued after 42 and 76 months because of possibly related side effects. A 32-year-old woman with mild acromegaly (IGF-I: 423 microg/l, GH after OGTT: 2.5 microg/l, adenoma 4 mm) was treated with cabergoline as primary therapy and reached safe GH levels (2 microg/l or less) and normal IGF-I levels with 3.5 mg cabergoline weekly. After 42 months of therapy the patient experienced a progressive decrease of libido, which she attributed to the intake of cabergoline. After stopping medication, serum levels of GH and IGF-I remained normal during the following 2.5 years. A 53-year-old man with moderate acromegaly (serum IGF-I: 547 microg/l, GH after OGTT: 5.9 microg/l, adenoma 7 mm) preferred cabergoline as primary therapy. Serum GH levels below 2 microg/l and normal levels of IGF-I were obtained with 3.5 mg cabergoline weekly. When the patient experienced severe stomach pains after 76 months of treatment, cabergoline was held responsible and discontinued. Serum GH and IGF-I did not increase again and stayed at the same level during a follow-up of 5.5 years. These two cases demonstrate that acromegalic patients with a good response to cabergoline may occasionally remain in remission after stopping therapy. This phenomenon has previously only been described in patients with a prolactinoma.

Optimalization and cost management of lanreotide-Autogel therapy in acromegaly.

BACKGROUND: Lanreotide-Autogel is a depot formulation of the somatostatin analog lanreotide used in the treatment of acromegaly. We investigated whether prolonging or shortening the interval between injections would offer any benefit. SUBJECTS AND METHODS: The interval was prolonged from once every 4 weeks to once every 6 weeks when patients (n=9) had normal IGF-I and GH concentrations. When patients (n=12) had still elevated IGF-I or GH on the maximal dose of 120 mg every 4 weeks, the interval was shortened to once every 3 weeks. Serum IGF-I and GH were measured after 12 and 24 weeks to allow for dose adaptation. Symptoms and tumor volume were evaluated at baseline and after 36 weeks. RESULTS: In seven of the nine subjects with normal IGF-I and GH, the interval could be extended to 6 weeks without loosing efficacy on IGF-I (195 vs 213 microg/l; not significant, NS) and GH concentrations (1.4 vs 1.3 microg/l; NS). The weekly dose could significantly be reduced (from 23.3 to 17.8 mg; P=0.002). In only 1 of the 12 not-controlled patients, reducing the interval to once every 3 weeks induced normalization of IGF-I and GH. CONCLUSION: In subjects whose acromegaly is well controlled using lanreotide-Autogel, prolonging the time interval between injections can often be increased 4 to 6 weeks without loss of efficacy, thereby improving the subject's comfort and reducing the cost of treatment. On the other hand, in subjects whose acromegaly is not controlled on a dose of 120 mg every 4 weeks, reducing the interval to every 3 weeks is rarely beneficial.

Impact of diabetes mellitus on the relationships between iron-, inflammatory- and oxidative stress status.

BACKGROUND: Diabetes is an inflammatory condition associated with iron abnormalities and increased oxidative damage. We aimed to investigate how diabetes affects the interrelationships between these pathogenic mechanisms. METHODS: Glycaemic control, serum iron, proteins involved in iron homeostasis, global antioxidant capacity and levels of antioxidants and peroxidation products were measured in 39 type 1 and 67 type 2 diabetic patients and 100 control subjects. RESULTS: Although serum iron was lower in diabetes, serum ferritin was elevated in type 2 diabetes (p = 0.02). This increase was not related to inflammation (C-reactive protein) but inversely correlated with soluble transferrin receptors (r = - 0.38, p = 0.002). Haptoglobin was higher in both type 1 and type 2 diabetes (p < 0.001) and haemopexin was higher in type 2 diabetes (p < 0.001). The relation between C-reactive protein and haemopexin was lost in type 2 diabetes (r = 0.15, p = 0.27 vs r = 0.63, p < 0.001 in type 1 diabetes and r = 0.36, p = 0.001 in controls). Haemopexin levels were independently determined by triacylglycerol (R(2) = 0.43) and the diabetic state (R(2) = 0.13). Regarding oxidative stress status, lower antioxidant concentrations were found for retinol and uric acid in type 1 diabetes, alpha-tocopherol and ascorbate in type 2 diabetes and protein thiols in both types. These decreases were partially explained by metabolic-, inflammatory- and iron alterations. An additional independent effect of the diabetic state on the oxidative stress status could be identified (R(2) = 0.5-0.14). CONCLUSIONS: Circulating proteins, body iron stores, inflammation, oxidative stress and their interrelationships are abnormal in patients with diabetes and differ between type 1 and type 2 diabetes.

Time course of oxidative stress status in the postprandial and postabsorptive states in type 1 diabetes mellitus: relationship to glucose and lipid changes.

OBJECTIVE: The aim of this study was to compare oxidative stress status (OSS) with blood glucose and lipid changes during the fasting, postprandial and postabsorptive phases in type 1 diabetes mellitus. METHODS: Twenty-three patients on intensive insulin treatment received a standard fat-rich breakfast and lunch. OSS was monitored at fasting (F), just after the post-breakfast glycemia peak (BP) (identified by continuous subcutaneous glucose monitoring), 3.5-h post-breakfast (B3.5), just after the post-lunch peak (LP), just after the post-lunch dale (LD) and 5 hours after lunch (L5). RESULTS: Whereas whole blood glutathione and plasma protein thiols increased in the postprandial period (from 6.52 +/- 1.20 (F) to 7.08 +/- 1.45 micromol/g Hb (BP), p = 0.005), ascorbate decreased gradually from 44 +/- 17 (F) to 39 +/- 19 micromol/L (LD), p = 0.015. Retinol and alpha-tocopherol also decreased from 27.1 +/- 7.0 (F) to 25.3 +/- 5.2 micromol/L (BP), p = 0.005. Uric acid decreased later, from 213 +/- 77 (BP) to 204 +/- 68 micromol/L (B3.5), p = 0.01, but then increased in LP (231 +/- 70 micromol/L) and LD to values higher than F (215 +/- 64, micromol/L, p = 0.01). Malondialdehyde increased gradually from 1.02 +/- 0.36 (F) to a maximum of 1.14 +/- 0.40 micromol/L (LP). In the postabsorptive phase (L5) all parameters except for thiols reverted to fasting concentrations. CONCLUSIONS: In type 1 diabetes lipid peroxidation increases during the postprandial phase in parallel to glucose and triglyceride changes. Blood antioxidants, however, followed diverse patterns of change.

Postprandial glucose monitoring in type 1 diabetes mellitus: use of a continuous subcutaneous monitoring device.

BACKGROUND: Pre-prandial glucose gives insufficient information on glycemic excursions throughout the day. We aimed to test a continuous subcutaneous glucose-monitoring device (GlucoDay) to describe postprandial glucose changes. METHODS: In 23 T1DM patients, 24-h GlucoDay registrations were started about 14 h before receiving a standard breakfast B and 3 h later lunch L. RESULTS: The 3-min glucose values were computed into parameters describing the postprandial changes after B and L. Two-hour glucose was higher after B (243 +/- 69 vs 180 +/- 79 mg/dL after L, p < 0.0001). Maximum glycemia (313 +/- 105 mg/dL after B and 304 +/- 119 after L, p < 0.0001) was higher and was reached after 78 and 57 min respectively. Three-hour AUC was higher but 30-min AUC was lower after B (5725 +/- 2414 vs 7488 +/- 2208 min mg/dL after L, p = 0.004). Glucose spikes (maximum peak minus fasting plasma glucose) were similar after B and L but the difference between maximum and minimum values was smaller after B (165 +/- 110 vs 219 +/- 115 mg/dL after L, p = 0.020). Duration of hyperglycemic periods >200, 140 or 126 mg/dL were not different after B or L, but time spent at glucose <100 mg/dL was longer after L (p < 0.0001). CONCLUSIONS: These results illustrate the use of subcutaneous glucose registration to characterize postprandial glycemia patterns in T1DM. Application of such methods to evaluate this and other clinical situations in DM can lead to therapeutic and dietary adjustments and ultimately improve glycemic control.

Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes: a randomized clinical trial.

OBJECTIVE: Insulin detemir is a soluble long-acting basal insulin analog designed to overcome the limitations of conventional basal insulin formulations. Accordingly, insulin detemir has been compared with NPH insulin with respect to glycemic control (HbA1c, prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration. RESEARCH DESIGN AND METHODS: People with type 1 diabetes (n = 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin. Insulin detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDet(morn+bed)) or at a 12-h interval (IDet(12h)). NPH insulin was administered before breakfast and at bedtime. Mealtime insulin was given as the rapid-acting insulin analog insulin aspart. RESULTS: With both insulin detemir groups, clinic fasting plasma glucose was lower than with NPH insulin (IDet(12h) vs. NPH, -1.5 mmol/l [95% CI -2.51 to -0.48], P = 0.004; IDet(morn+bed) vs. NPH, -2.3 mmol/l (-3.32 to -1.29), P < 0.001), as was self-measured prebreakfast plasma glucose (P = 0.006 and P = 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P = 0.046; 32%, P = 0.002; respectively) compared with NPH insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDet(morn+bed) group (P < 0.001). Although HbA1c for each insulin detemir group was not different from the NPH group, HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference -0.18% [-0.34 to -0.02], P = 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P < 0.001). The NPH group gained weight during the study, but there was no change in weight in either of the insulin detemir groups (IDet(12h) vs. NPH, -0.8 kg [-1.44 to -0.24], P = 0.006; IDet(morn+bed) vs. NPH, -0.6 kg [-1.23 to -0.03], P = 0.040). CONCLUSIONS: Overall glycemic control with insulin detemir was improved compared with NPH insulin. The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person's needs.