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1.
Diabetes Metab Syndr ; 17(11): 102899, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37939435

ABSTRACT

AIMS: The aim of this review is to give an update of the recent advances in the pathophysiology, prognosis, diagnosis and treatments of cystic fibrosis-related diabetes (CFRD). METHODS: The literature survey focuses on original and review articles dealing with CFRD between 2006 and 2023, and in particular with: pathophysiology, risk and predictive factors, screening, chronic complications of CFRD, management and the effects of CFTR channel modulator therapies on glucose homeostasis, using PubMed®. RESULTS: The rising prevalence of CFRD is due to prolonged life survival among patients with cystic fibrosis (CF). Advances in the understanding of the pathophysiology highlight the singularity of CFRD. Adherence to diagnostic guidelines remains challenging. Besides the classical OGTT, alternative diagnostic tests are being considered: HbA1c measurement, continuous glucose monitoring (CGM), intermediate measurements of alternative glucose tolerance stages through OGTT and homeostatic model assessment (HOMA). Early treatment of (pre)diabetes in CF patients is mandatory. The advent of CFTR channel modulator therapies have created a paradigm shift in the management of CF: they seem to improve glucose homeostasis, but the mechanism remains unclear. CONCLUSION: CFRD management is an ongoing concern. Optimal care has reduced the negative impact of CFRD on lung function, nutrition, and survival. Increasing prevalence of CFRD and prolonged lifespan lead to more microvascular complications. New screening tools (Hba1c, CGM, HOMA) show potential for better classification of patients. The effect of CFTR modulators on glucose metabolism warrants further research.


Subject(s)
Cystic Fibrosis , Diabetes Mellitus , Glucose Intolerance , Humans , Glucose Intolerance/epidemiology , Cystic Fibrosis/complications , Glycated Hemoglobin , Blood Glucose Self-Monitoring/adverse effects , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Glucose Tolerance Test , Blood Glucose/metabolism , Diabetes Mellitus/diagnosis
2.
Acta Gastroenterol Belg ; 85(2): 346-357, 2022.
Article in English | MEDLINE | ID: mdl-35709779

ABSTRACT

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the evidence of steatosis in the setting of a metabolic risk condition such as type 2 diabetes mellitus (T2DM). Indeed, T2DM and liver steatosis share common pathophysiological mechanisms, and one can lead to the other. MAFLD can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis as well as hepatocellular carcinoma (HCC). Because of the lack / disparity of guidelines for MAFLD screening, which is asymptomatic in its early stages, it is not rare that diabetic patients are belatedly diagnosed with NASH cirrhosis or HCC. We therefore recommend systematic non-invasive tests (NITs) that calculate an estimate of the risk based on readily available anthropometric and biological parameters. These include the fatty liver index (FLI) for steatosis detection and at least one of the following for fibrosis: non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4) or Hepamet fibrosis score (HFS). Indeed, NFS and FIB-4 are the best predictors of liver-related events, while FIB-4 and HFS correlate with overall mortality. Systematic literature review found only few retrospective or cross-sectional studies using NITs for systematic steatosis and fibrosis screening in T2DM patients, with a crucial need for prospective studies. This screening strategy will allow targeted patients to be referred for further liver investigation (e.g. ultrasound, elastometry) and care. Current treatment modalities of MAFLD in T2DM patients range from lifestyle and dietary interventions to specific glucose-lowering drugs that recently showed some benefits regarding MAFLD, such as pioglitazone, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Other treatments are currently under investigation.


Subject(s)
Carcinoma, Hepatocellular , Diabetes Mellitus, Type 2 , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Sodium-Glucose Transporter 2 Inhibitors , Carcinoma, Hepatocellular/drug therapy , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Glucose/therapeutic use , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/therapy , Liver Neoplasms/drug therapy , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/therapy , Prospective Studies , Retrospective Studies , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
3.
Diabetes Metab Syndr ; 14(2): 65-69, 2020.
Article in English | MEDLINE | ID: mdl-31991294

ABSTRACT

We conducted a prospective observational study to evaluate the medium-term impact of the flash glucose monitoring system (FGM) in a type 1 diabetic population. We included 248 patients, switched from conventional blood glucose monitoring (BGM) to FGM. We evaluated glycaemic control at 2-4 (T1) and 5-11 (T2) months after initiation and at the last available visit (T3, 18 ± 4 months). We asked patients to fill in, at T0 and T2, two questionnaires based on the Diabetes Treatment Satisfaction Questionnaire; and on the Hypoglycaemia Fear Survey. Glycaemic control improved, from 8.1 ± 1.3% at T0 to 7.8 ± 1.2% at T1 (p < 0.001) and remained unchanged after. Average number of controls increased from 3.2 ± 1.2 BGM to 7.7 ± 3.9 at T1 (p < 0.001). We observed a modest decrease in daily insulin doses. We evidenced an increase in mild hypoglycaemic events, especially in well-controlled subjects, but no increase of severe events. Satisfaction score improved from 30.5 ± 7.7 points to 38.3 ± 5.1 points (p = 0.018), was correlated with the reduction in and was higher in less controlled patients at inclusion. "Behaviour" score regarding hypoglycaemias decrease from 5.7 ± 4.1 to 4.4 ± 3.6 points (p < 0.001). In conclusion, this 18-months study trial indicates that using the FGM technology in patients with T1D may improve glycaemic control, in real-life conditions, especially in less controlled patients. FGM was associated with an increase of patients' satisfaction regarding treatment. Hypoglycaemic events, however, were not reduced in frequency. Therefore, the need for an educational team and a structure program in the management of this new technology remains mandatory.


Subject(s)
Diabetes Mellitus, Type 1/blood , Glucose/analysis , Hypoglycemia/prevention & control , Monitoring, Ambulatory/instrumentation , Adult , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/psychology , Female , Follow-Up Studies , Humans , Hypoglycemia/psychology , Male , Middle Aged , Patient Satisfaction , Prospective Studies , Quality of Life
4.
Diabetes Metab ; 46(2): 83-88, 2020 04.
Article in English | MEDLINE | ID: mdl-31055056

ABSTRACT

Insulin degludec is a new ultra-long-action basal insulin. Using treat-to-target protocols, controlled trials have shown comparable HbA1c reductions with insulin degludec and comparators in both type 1 and type 2 diabetes. Most studies identify, however, better control of fasting plasma glucose with insulin degludec vs. either insulin glargine U100 or detemir, and all have consistently demonstrated clinically relevant decreases in (nocturnal) hypoglycaemic episodes. These characteristics have provided added therapeutic value for insulin degludec in clinical practice. Thus, the aim of this review is to discuss, within the context of randomized and observational studies, the clinical effects of insulin degludec use in type 1 and type 2 diabetes.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin, Long-Acting/therapeutic use , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Drug Administration Schedule , Glycated Hemoglobin/analysis , Humans , Observational Studies as Topic , Randomized Controlled Trials as Topic , Treatment Outcome
5.
Diabetes Metab Syndr ; 13(1): 332-336, 2019.
Article in English | MEDLINE | ID: mdl-30641721

ABSTRACT

AIM: We evaluate retrospectively long-term effects of GLP-1 receptor agonists in type 2 diabetic patients treated between 2008 and 2016. METHODS: 131 patients treated by GLP-1 receptor agonists (GLP-1RAs) were included. The objective was to evaluate the evolution of glycated hemoglobin (HbA1c) during a period up to 4 years. The secondary objectives consisted of analysing the long-term effects of treatment on body mass index (BMI), blood pressure and lipids; reporting the proportion of patients who reached HbA1c objectives; estimating the time before treatment failure and determining predictive factors of failure. We also compared twice-daily exenatide to once-daily liraglutide on the major parameters. RESULTS: HbA1c improved significantly, mostly during the first year of treatment (-1.2%), and this effect was maintained after 4 years (-1.4% vs. baseline). At 1 year, 26% and 47% of subjects achieved HbA1c levels <7.0% and 7.5%, respectively. Treatment failure was observed in 51% of patients after a mean duration of GLP-1RA treatment of 50 months. Half of patients had failed after 42 months. Baseline HbA1c greater than 9.0% and male gender were predictive factors of treatment failure. BMI also decreased: -0.9 kg/m2 the first year, -1.9 kg/m2 after 4 years. No significant difference was found between patients treated with exenatide and liragutide over time. CONCLUSIONS: The beneficial effects of GLP-1RAs on HbA1c reached a plateau after the first year of treatment and are maintained at 4 years only in one third of patients. Failure occurred predominantly in men with a baseline HbA1c greater than 9%.


Subject(s)
Biomarkers/analysis , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/therapeutic use , Blood Glucose/analysis , Diabetes Mellitus, Type 2/metabolism , Female , Follow-Up Studies , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged , Prognosis , Retrospective Studies
8.
Br J Dermatol ; 171(1): 155-61, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24506139

ABSTRACT

BACKGROUND: A few case reports suggest that incretin-based therapies could improve psoriasis in patients with type 2 diabetes, the mechanism(s) of which remain unclear. OBJECTIVES: To determine the effects after 16-20 weeks of treatment with a glucagon-like peptide (GLP)-1 analogue on clinical severity and histopathological aspects of psoriasis in patients with type 2 diabetes, and to examine the presence of γδ T cells and the expression of interleukin (IL)-17 in psoriasis before and after treatment. METHODS: Seven patients with type 2 diabetes and psoriasis were followed. Psoriasis Area and Severity Index (PASI) was measured at baseline (T0) and after 7 ± 1 (T1) and 18 ± 2 (T2) weeks' treatment with exenatide/liraglutide. The histopathological pattern of psoriasis, and flow cytometry and immunological data (γδ T-cell percentage and IL-17 expression) were obtained from psoriatic and control sites. RESULTS: The mean PASI decreased from 12·0 ± 5·9 to 9·2 ± 6·4 (P = 0·04). Histological analysis showed a reduction in epidermal thickness after treatment. The dermal γδ T-cell percentage was higher in psoriatic lesions than in control specimens (P = 0·03), as was IL-17 expression (P = 0·018). A reduction of γδ T cells from 6·7 ± 4·5% to 2·7 ± 3·8% (P = 0·05) was demonstrated in the six patients with improved/unchanged PASI. A correlation between PASI and γδ T-cell percentage evolution during therapy (T2-T0) was noted (r = 0·894, P = 0·007). IL-17 was reduced in the four patients with the highest PASI reductions. CONCLUSIONS: The administration of a GLP-1 analogue improved clinical psoriasis severity in patients with type 2 diabetes. This favourable outcome was associated with a decrease of dermal γδ T-cell number and IL-17 expression. Further studies are needed to establish long-term efficacy in (diabetic) patients with psoriasis.


Subject(s)
Diabetes Mellitus, Type 2/complications , Glucagon-Like Peptide 1/analogs & derivatives , Hypoglycemic Agents/therapeutic use , Incretins/therapeutic use , Peptides/therapeutic use , Psoriasis/drug therapy , Venoms/therapeutic use , Adult , Chronic Disease , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/immunology , Exenatide , Female , Glucagon-Like Peptide 1/therapeutic use , Humans , Interleukin-17/metabolism , Liraglutide , Lymphocyte Count , Male , Middle Aged , Prospective Studies , Psoriasis/complications , Psoriasis/immunology , Severity of Illness Index , Skin/immunology , T-Lymphocytes/metabolism , Treatment Outcome
9.
Acta Clin Belg ; 67(4): 250-4, 2012.
Article in English | MEDLINE | ID: mdl-23019799

ABSTRACT

The aim of this multicentre and observational study was to evaluate in a real life setting glycated haemoglobin A1(c), (HbA1c) as well as body weight outcomes in patients with type 2 diabetes in whom insulin was initiated after unsatisfactory response to exenatide, combined with maximal dosages of metformin and a sulfonylurea. We included 81 patients. In 56 patients, data were available after 6-8 and in 42 after 9-12 month's follow-up. Age and duration of diabetes were 57 +/- 11 and 11 +/- 6 years, respectively. Body mass index (BMI) was 32.4 +/- 6.9 kg/m2. Insulin was initiated with a basal insulin injection (22%), premixed insulin injections (48%) or a basal prandial scheme (30%). In the 6-8 and 9-12 month's cohorts, HbA(1c) decreased from 9.3 +/- 1.4 to 8.2 +/- 1.2% and from 9.3 +/- 1.3 to 8 +/- 1.1%, respectively (p < 0.0001). However, only 9 and 12% of subjects reached a target HbA(1c) of less than 7.0%, respectively. About half of the patients had HbA(1c) levels equal or higher than 8.0%. Insulin doses were progressively increased during the follow-up period. Insulin treatment was associated with a significant body weight increase (5-7 kg) (p < 0.0001). In conclusion, a high proportion of patients remained above the HbA(1c) targets after 6-12 month's treatment, despite a progressive increase in insulin dosages. Insulin treatment was associated with a marked weight gain.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Peptides/therapeutic use , Venoms/therapeutic use , Weight Gain , Diabetes Mellitus, Type 2/blood , Exenatide , Female , Glycated Hemoglobin/analysis , Humans , Male , Metformin/administration & dosage , Middle Aged
10.
Diabetes Metab ; 38(1): 86-8, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22227407

ABSTRACT

CONTEXT AND AIM: Psoriasis is an immune-mediated skin disorder frequently associated with obesity and type 2 diabetes (T2D). This report is of a clinically significant improvement in psoriasis lesions in a patient with T2D during treatment with a GLP-1 receptor agonist (exenatide). OBSERVATION: A 61-year-old male patient (BMI: 25.5 kg/m(2)) with T2D treated with metformin and sulphonylureas had also complained, since 1980, of extensive psoriasis that required multiple steroid-based treatments [Psoriasis Area and Sensitivity Index (PASI) score: 11]. In September 2008, his diabetes treatment was intensified with exenatide (Byetta(®)) to improve poor glycaemic control. The patient, as expected, lost weight and reduced HbA(1c) levels from 65 mmol/mol to 56 mmol/mol. However, after just 1 month of treatment with exenatide, the patient also reported a dramatic improvement in psoriatic plaques that was confirmed at the 1-year follow-up (PASI: estimated at 3-4). Withdrawal of exenatide was associated with weight gain, deterioration of glycaemic control and deterioration of psoriasis (PASI:>10). After reinstating exenatide treatment, the patient again reported a prompt improvement in psoriasis (PASI: 3.1). CONCLUSION: There was a major and rapid improvement in psoriasis in our patient with T2D following treatment with exenatide. A possible mechanism might be through direct modulation of the immune system by GLP-1 receptor agonists.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Natural Killer T-Cells/metabolism , Peptides/therapeutic use , Psoriasis/drug therapy , Receptors, Glucagon/agonists , Venoms/therapeutic use , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/immunology , Dose-Response Relationship, Drug , Exenatide , Glucagon-Like Peptide-1 Receptor , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/pharmacology , Male , Middle Aged , Natural Killer T-Cells/drug effects , Natural Killer T-Cells/immunology , Peptides/pharmacology , Psoriasis/blood , Psoriasis/immunology , Treatment Outcome , Venoms/pharmacology
11.
Acta Clin Belg ; 67(6): 411-5, 2012.
Article in English | MEDLINE | ID: mdl-23340146

ABSTRACT

OBJECTIVE: We prospectively analysed HbA1c changes after 12 months of exenatide therapy and determined which baseline clinical and/or biological factors predict response. RESEARCH DESIGN AND METHODS: Open-label cohort of 41 subjects with type 2 diabetes (56% male) poorly-controlled on maximally-tolerated oral dual therapy. Age (mean ± 1SD) was 60 ± 10 years, and known diabetes duration 11 ± 8 years (mean ± 1SD). Biometric changes in weight, body mass index (BMI), waist circumference (WC), HOMA modeling (Homeostasis Model Assessment) of ß-cell function (HOMA-B) and insulin sensitivity (HOMA-S) as well as in HbA1c were assessed at baseline, and after 6 or 12 months exenatide therapy. Patients were divided into three groups: goal-achievers (GA, n = 15), defined as achieving HbA1c ≤ 7.5% (58 mmol/mol) at 12 months; nongoal- achievers (NGA, n = 16; HbA1c > 7.5% (58 mmol/mol) at 12 months); and primary failure to exenatide therapy (early lack of efficacy; PF, n = 9). Non-responders represented the combined NGA plus PF patients. RESULTS: The addition of exenatide to maximally-tolerated oral dual therapy led to target HbA1c attainment (≤ 7.5% (58 mmol/mol) at 1 year) in 37% of cases, associated with reduction in weight, BMI and waist circumference. GA were older than non-responders (64 ± 9 vs. 57 ± 10 years, p = 0.032). Diabetes duration was comparable. Baseline HbA1c was significantly lower in GA (8.3 ± 0.9 vs. 9.5 ± 0.9% in non-responders; p < 0.001). Baseline HOMA-B and HOMA-S were comparable, while HOMA product (BxS) was higher in GA (17 ± 6 vs. 14 ± 6% in non- responders, p = 0.04). At 12 months, HbA1c reached 7.0 ± 0.6% in GA vs. 9.0 ± 1.3% in non-responders. Weight, BMI and waist circumference decreased in both groups. In GA and non-responders, there was a marked relationship between baseline HbA1c and absolute decrement in HbA1c over the study period. Logistic regression demonstrated that baseline HbA1c was the strongest predictor for target attainment following exenatide therapy (p < 0.001), with age to a lesser degree (p = 0.089). CONCLUSION: Baseline HbA1c is a major predictor of response to exenatide treatment, defined as target HbA1c (≤ 7.5%, 58 mmol/mol) attainment. The lower the baseline HbA1c, the greater the likelihood of reaching the target HbA1c at 12 months, even though patients with higher baseline HbA1c benefited from the largest absolute reduction in HbA1c levels.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Peptides/therapeutic use , Venoms/therapeutic use , Anthropometry , Belgium , Biometry , Exenatide , Female , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/administration & dosage , Insulin Resistance , Male , Middle Aged , Peptides/administration & dosage , Prospective Studies , Treatment Failure , Venoms/administration & dosage , Weight Loss/drug effects
12.
Acta Clin Belg ; 66(5): 387-9, 2011.
Article in English | MEDLINE | ID: mdl-22145277

ABSTRACT

Hemiballism-hemichorea is characterized by non-patterned and involuntary unilateral movements. It is a rare clinical sign unmasking type 2 diabetes mellitus, mostly in elderly patients. We report the clinical and neuroimaging findings of a patient admitted for hemiballism-hemichorea of the right upper limb, leading to the diagnosis of type 2 diabetes. We hereby describe clinical and neuroimaging findings. After initiation of treatment and restoration of euglycaemia, we note a complete remission of the initial neurological symptoms.


Subject(s)
Brain/pathology , Diabetes Complications/diagnosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Dyskinesias/etiology , Aged, 80 and over , Brain/diagnostic imaging , Chorea/etiology , Diabetes Complications/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Female , Functional Laterality , Humans , Hypoglycemic Agents/therapeutic use , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Treatment Outcome
13.
Horm Metab Res ; 43(4): 287-91, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21264796

ABSTRACT

We studied a 55-year old woman presenting with features of Cushing's syndrome associated with metabolic abnormalities including severe hypertension and type 2 diabetes. Urinary free cortisol excretion was within normal limits, but an unusual diurnal cortisol rhythm was observed with low morning and high postprandial levels, associated with the absence of cortisol suppression after dexamethasone, suggesting the possibility of GIP-dependent Cushing's syndrome. The diagnosis was confirmed by further investigations, showing significant plasma cortisol responses after a mixed meal test and after oral, but not intravenous glucose administration, as well as ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH). An aberrant increase in cortisol was also observed after glucagon and terlipressin injections. The patient was first treated with octreotide 100-250 µg thrice daily for 6 months, then with the new multi-ligand somatostatin analogue (SOM 230) 450-900 µg twice daily for 3 months. Although inducing a significant acute suppression of post-prandial cortisol response, both drugs had no effects on the clinical and metabolic abnormalities associated with Cushing's syndrome and new tests performed at the end of each treatment period confirmed escape of post-meal cortisol suppression to therapy. The patient finally underwent a bilateral adrenalectomy, which markedly improved her medical condition and allowed in vitro confirmation by real time RT-PCR quantification of a high aberrant expression of GIP receptor mRNA in adrenal tissue. This case report illustrates the lack of sustained efficacy of somatostatin analogues on GIP-dependent Cushing's syndrome, independent of their affinity for the different somatostatin receptor subtypes.


Subject(s)
Cushing Syndrome/drug therapy , Gastric Inhibitory Polypeptide/metabolism , Octreotide/administration & dosage , Somatostatin/analogs & derivatives , Adrenalectomy , Cushing Syndrome/genetics , Cushing Syndrome/metabolism , Cushing Syndrome/surgery , Female , Humans , Middle Aged , Receptors, Gastrointestinal Hormone/genetics , Receptors, Gastrointestinal Hormone/metabolism , Somatostatin/administration & dosage
14.
Diabetes Metab ; 36(5): 381-8, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20598606

ABSTRACT

AIM: The study objective was to analyze, in everyday practice, the long-term metabolic effects of exenatide (for 9 and 12 months) in patients with type 2 diabetes not responding to treatments with metformin and sulphonylurea at maximum dosages. METHODS: A total of 299 type 2 diabetics were recruited from 14 centres specializing in diabetes care across Belgium. Main study endpoints were changes in HbA(1c), weight and waist circumference, and tolerability and compliance. Two patient cohorts were analyzed for effectiveness, with data available at 9 (n=90) and 12 (n=94) months of follow-up. RESULTS: Significant decreases in HbA(1c) of -1.3% and -1.6% were observed in the 9- and 12-month cohorts, respectively (P<0.001). The decrease in HbA(1c) was greater in patients with higher baseline levels (P<0.001), and the response was independent of baseline weight, body mass index (BMI), age, gender and diabetes duration. A progressive reduction of weight (4.9 kg) was also observed in the two cohorts at 9 and 12 months (P<0.001), with greater weight loss in patients with higher baseline BMI (P=0.046) and in female subjects (P=0.025). Waist circumference also decreased from baseline to endpoints. A correlation was observed between reduction in HbA(1c) and weight loss (P=0.019). Side effects, mainly of gastrointestinal origin, were reported in 33% (93/284 patients in the safety cohort). The rate of hypoglycaemia was 3.5%. Treatment was discontinued in 27% of patients (n=77) mainly due to drug inefficacy (53%, n=41) or adverse events (26%, n=20), or both (8%, n=6). CONCLUSION: Exenatide leads to long-term improvement of glycaemic control as well as weight loss in a majority of patients not responding to combined oral drug therapy in real-world clinical practice. However, no baseline factors predictive of response could be identified. Exenatide can be considered an effective treatment option in such patients, including those with high baseline HbA(1c) and long duration of diabetes.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Peptides/therapeutic use , Venoms/therapeutic use , Aged , Body Mass Index , Diabetes Mellitus, Type 2/blood , Exenatide , Female , Gastrointestinal Diseases/chemically induced , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/epidemiology , Male , Middle Aged , Peptides/adverse effects , Retrospective Studies , Time Factors , Treatment Outcome , Venoms/adverse effects , Waist Circumference , Weight Loss
15.
Diabetes Metab ; 36(4): 293-8, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20447851

ABSTRACT

OBJECTIVE: This study aimed to determine whether or not the improvement of glycaemic control with 6-month exenatide therapy in type 2 diabetic patients with secondary failure to combined oral therapy is related to amelioration of ß-cell function and/or insulin sensitivity and their combined product. RESEARCH DESIGN AND METHODS: Thirty-three patients with type 2 diabetes were investigated. Their ß-cell function and insulin sensitivity were measured using Homoeostasis Model Assessment [HOMA-B, HOMA-S and HOMA hyperbolic product (BxS)]. Additional endpoints included changes in weight, HbA(1c) and plasma adiponectin, as well as baseline clinical and biological characteristics, as potential predictors of HbA(1c) response. RESULTS: After 6 months, unadjusted HOMA-B increased from 33 ± 24% to 43 ± 23% (P=0.0210), whereas there was no significant change in HOMA-S (from 58 ± 35% to 61 ± 40%). The hyperbolic product increased by a relative 70% (from 15 ± 7% to 22 ± 15%; P=0.0055). Body mass index decreased from 32.2 ± 5.1 kg/m(2) to 31.0 ± 4.8 kg/m(2) (P<0.0001) and HbA(1c) from 8.8 ± 1.0% to 7.6 ± 1.2% (P<0.0001). No change was observed in adiponectin concentrations. Higher baseline HbA(1c) values were a significant predictor of therapeutic response. CONCLUSION: Exenatide significantly increased HOMA-B and hyperbolic product over a 6-month treatment period with no overall change in insulin sensitivity, despite weight loss. Thus, improved ß-cell function rather than increased insulin sensitivity accounts for the bulk of HbA(1c) reduction following 6 months of exenatide treatment.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin-Secreting Cells/metabolism , Insulin/metabolism , Peptides/therapeutic use , Venoms/therapeutic use , Adult , Aged , Biomarkers/blood , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/metabolism , Drug Administration Schedule , Exenatide , Female , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacology , Male , Middle Aged , Peptides/administration & dosage , Peptides/pharmacology , Predictive Value of Tests , Risk Factors , Time Factors , Treatment Outcome , Venoms/administration & dosage , Venoms/pharmacology
16.
Acta Clin Belg ; 64(1): 49-55, 2009.
Article in English | MEDLINE | ID: mdl-19317241

ABSTRACT

AIM: PREDICTIVE (Predictable Results and Experience in Diabetes Through Intensification and Control to Target: an International Variability Evaluation) is a multi-national study designed to evaluate the safety and efficacy of insulin detemir (Levemir) in "real world" medical practice. The aim of the study is to report the PREDICTIVE results of the Belgian type 1 diabetic cohort. METHODS: Two hundred and thirty-two patients treated with a basal-bolus insulin scheme were considered for analysis. Seventy-eight percent of those patients were previously treated with insulin glargine as a basal insulin, while 22% received NPH, before switching to Levemir. RESULTS: Mean age and duration of diabetes were 45 +/- 15 and 18 +/- 13 years, respectively (means +/- SD). HbA1C was 8.3 +/- 1.2%. We observed (at weeks 12 and 26 after baseline) a significant reduction in all hypoglycaemic events including major hypoglycaemias after switching to detemir (p < 0.0007). There was no change in HbA1C. Fasting blood glucose decreased from 170 +/- 49 to 158 +/- 45 mg/dl at week 26 (p < 0.009), while fasting blood glucose variability was reduced from 69 +/- 35 to 57 +/- 30 mg/dl at week 26 (p < 0.0001). Total insulin doses increased during the trial from 0.74 +/- 0.28 to 0.82 +/- 0.14 U/kg/day (p < 0.0001). No weight gain was observed during the study. Patient's satisfaction increased significantly (from 6.3 +/- 1.5 to 7.2 +/- 1.6 at week 26, p < 0.0007). CONCLUSION: This report from the Belgian cohort of PREDICTIVE extends the safety and efficacy data of insulin detemir in type 1 diabetic patients treated with a basal-bolus insulin scheme.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/analogs & derivatives , Adult , Belgium , Female , Follow-Up Studies , Humans , Insulin/therapeutic use , Insulin Detemir , Insulin, Long-Acting , Male , Middle Aged , Treatment Outcome
17.
Diabetes Metab ; 34(1): 62-7, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18069029

ABSTRACT

It is now emerging that, in patients who are at high risk for cardiovascular complications and, in particular, those with diabetes, the occurrence of late restenosis and thrombosis after treatment of coronary artery disease with drug-eluting stents is higher than earlier reports have suggested. Therefore, the aim of this study was to assess the prevalence of in-stent restenosis in a cohort of consecutive patients with diabetes treated for coronary disease in 2005 with drug-eluting stents [either sirolimus (58%) or paclitaxel (42%)]. The duration of follow-up was 9.0+/-3.4 months [mean+/-1 standard deviation (S.D.)]. A total of 154 patients (type 2 diabetes: 91%) were included in the study (age: 66+/-10 years), and the total number of implanted stents was 184. Two subjects died from cardiac causes, while myocardial infarction and (un)stable angina were observed in 3 (2%) and 39 (25%) patients, respectively. In-stent restenosis, appraised by angiography, was observed in 17 individuals (11%) after a mean follow-up of five months. Mean HbA(1c) in patients with restenosis was 7.6+/-1.8%. There was no difference in the rate of restenosis with sirolimus-(n=8) compared with paclitaxel-(n=9) eluting stents. Male gender, oral therapy for diabetes and stent diameter were predictors of in-stent restenosis. In conclusion, even over a medium-term period, in-stent restenosis remains a potential risk for coronary diabetic patients treated with drug-eluting devices.


Subject(s)
Coronary Restenosis/epidemiology , Coronary Stenosis/therapy , Diabetic Angiopathies/therapy , Drug-Eluting Stents , Sirolimus/therapeutic use , Aged , Cohort Studies , Coronary Restenosis/mortality , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 2/therapy , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Retrospective Studies , Survival Analysis , Treatment Outcome
18.
Acta Clin Belg ; 61(3): 127-33, 2006.
Article in English | MEDLINE | ID: mdl-16881561

ABSTRACT

The aim of our study was to analyse the quality of metabolic and blood pressure control in a cohort of 101 patients with type 2 diabetes (54 males; 47 females), previously followed in primary care settings and admitted for the first time to the diabetes centres of Saint-Luc (n=66) or Mont-Godinne (n=35) University Hospitals. Age and (known) duration of diabetes were 64 +/-12 and 6 +/- 7 years (mean +/- SD), respectively. Body mass index was 31 +/- 7 kg/m2. Systolic and diastolic blood pressures were 140 +/-12 and 81 +/-11 mmHg. Homeostasis model assessment (HOMA) showed insulin sensitivity at 63 +/-32% and P-cell function at 49 +/- 44% (n=34). Forty-seven percent of patients received either diet alone or combined with an oral antidiabetic monotherapy. Seven-teen percent of all patients were on insulin monotherapy or associated with oral drugs. HbAlc was 9.0 +/- 2.3%, with 22% of patients within HbAlc targets of < or = 7%. Only a subset of patients reached international targets of care in terms of blood pressure and lipidic profile, despite antihypertensive and lipid-lowering agents in 62% and 36% of patients, respectively. Forty-five percent of individuals had at least one diabetes-related long-term complication. In view of this unsatisfactory control, our results suggest that "anti-diabetic" treatment should be intensified earlier in primary care settings.


Subject(s)
Blood Glucose/metabolism , Blood Pressure/physiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Lipids/blood , Aged , Blood Pressure Determination , Diagnostic Tests, Routine , Female , Follow-Up Studies , Glycated Hemoglobin/metabolism , Humans , Male , Patient Admission , Prognosis , Retrospective Studies , Severity of Illness Index
19.
Acta Clin Belg ; 57(3): 148-53, 2002.
Article in French | MEDLINE | ID: mdl-12212356

ABSTRACT

The aim of this study was to report the clinical characteristics of 13 patients with Hürthle carcinoma. In the vast majority of them, disease was suspected by a palpable thyroid nodule. The results of preoperative examination (scintigraphy, ultrasonography, thyroglobulin) are also discussed as well as the pathological aspects and follow-up characteristics after total thyroidectomy.


Subject(s)
Adenoma, Oxyphilic/pathology , Thyroid Neoplasms/pathology , Adenoma, Oxyphilic/diagnosis , Adenoma, Oxyphilic/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/surgery , Thyroidectomy
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