Advances in cystic fibrosis-related diabetes: Current status and future directions.

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.

1-h post-load plasma glucose for detecting early stages of prediabetes.

Prediabetes is a very prevalent condition associated with an increased risk of developing diabetes and/or other chronic complications, in particular cardiovascular disorders. Early detection is therefore mandatory since therapeutic interventions may limit the development of these complications. Diagnosis of prediabetes is currently based on glycemic criteria (fasting plasma glucose (PG), and/or glycemia at 120 min during a 75 g oral glucose tolerance test (OGTT) and/or glycated hemoglobin (HbA1c). Accumulating longitudinal evidence suggests that a 1-hour PG ≥155 mg/dl (8.6 mmol/l) during the OGTT is an earlier marker of prediabetes than fasting PG, 2-h post-load PG, or HbA1c. There is substantial evidence demonstrating that the 1-h post-load PG is a more sensitive predictor of type 2 diabetes, cardiovascular disease, microangiopathy and mortality compared with conventional glucose criteria. The aim of this review is to highlight the paramount importance of detecting prediabetes early in its pathophysiological course. Accordingly, as recommended by an international panel in a recent petition, 1-h post-load PG could replace current criteria for diagnosing early stages of "prediabetes" before prediabetes evolves as conventionally defined.

Impact of flash glucose monitoring on glycaemic control and quality of life in patients with type 1 diabetes: A 18-month follow-up in real life.

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.

Current status of insulin degludec in type 1 and type 2 diabetes based on randomized and observational trials.

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.

Long-term effects of GLP-1 receptor agonists in type 2 diabetic patients: A retrospective real-life study in 131 patients.

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%.

Predicting factors of hypoglycaemia in elderly type 2 diabetes patients: Contributions of the GERODIAB study.

The burden of hypoglycaemia is important, particularly in elderly type 2 diabetes (T2D) patients. Unfortunately, however, few studies are available concerning this population. GERODIAB is a prospective, multicentre, observational study that aims to describe the 5-year morbidity and mortality of 987 T2D patients aged 70 years and older. After analyzing the frequency of and factors associated with hypoglycaemia in the 6 months prior to study inclusion, it was found that hypoglycaemia was associated with retinopathy, lower levels of LDL cholesterol and altered mini-Geriatric Depression Scale (GDS) scores.

Improvement of psoriasis during glucagon-like peptide-1 analogue therapy in type 2 diabetes is associated with decreasing dermal γδ T-cell number: a prospective case-series study.

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.

Diabetes and cancer: a 2013 synopsis.

Diabetes, in particular type 2 diabetes, and cancer are two diseases that appear to be associated. Numerous epidemiological studies indicate indeed that diabetes increases the incidence of several tumors. Chronic hyperglycemia and/or insulin resistance with compensatory hyperinsulinemia could account for the association. On the other hand, the interpretation of the link between diabetes and cancer could be influenced by therapeutical interferences. Considering all these data together, cancer should be considered as a "new potential complication" of diabetes and integrated in the follow-up of diabetic subjects.

Glycemic control and weight changes in patients with type 2 diabetes intensified to three insulin regimens after therapeutic failure to exenatide.

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.

[Knowledge of the general population about hypertension and diabetes mellitus in South Kivu, Democratic Republic of Congo]. / Connaissances de la population générale sur l'hypertension artérielle et le diabète sucré au Sud-Kivu, République démocratique du Congo.

BACKGROUND: In the Democratic Republic of Congo (DRC), a country in a post-conflict period, high priority cannot be given to non-communicable diseases other than to emergencies. This certainly involves inadequacy in raising awareness for prevention of these diseases. OBJECTIVE: To evaluate the level of knowledge of the Congolese general population on hypertension and diabetes mellitus. METHODS: Responses to a questionnaire from 3% of the general population aged 15 and older in the city of Bukavu and two rural areas: Hombo and Walungu (South Kivu, eastern DRC), recruited after stratification by ward in the city of Bukavu and a group of prone villages were expected. The questions focused on identification, testing, causes, complications and treatment of hypertension and diabetes mellitus. RESULTS: Of the 7770 respondents, screening for hypertension and diabetes mellitus affected only 14.9% and 7.3% of subjects respectively. Knowledge of these two conditions was generally low in the general population, although better in the subgroups of patients and those with higher socioeconomic level (P<0.05). Use of the medias was also associated with better knowledge (P<0.05). CONCLUSIONS: This study shows that knowledge about hypertension and diabetes mellitus and their testing in South Kivu is low. It is imperative that the Congolese government includes non-communicable diseases in its priorities of the millennium. Similarly, the WHO should actively contribute to screening for them in low-income countries.

Improvement of psoriasis during exenatide treatment in a patient with diabetes.

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.

Predictive factors associated with primary failure to exenatide and non goal attainment in patients with type 2 diabetes.

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.

Hemiballism revealing type 2 diabetes in an elderly: clinical and neuroimaging findings and etiopathogenic links.

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.

Exenatide improves weight loss insulin sensitivity and ß-cell function following administration to a type 2 diabetic HIV patient on antiretroviral therapy.

The use of retroviral drugs in the treatment of infection by human immunodeficiency virus (HIV) is associated, especially for first generations, with side effects such as lipodystrophy, fatty liver and insulin resistance, which may trigger secondary diabetes or worsen existing diabetes. The use of Glucagon-Like Peptide-1 in obese patients with type 2 diabetes on HIV retroviral as an alternative to insulin therapy is not documented; we report the case of a 47-year-old treated with exenatide when insulin was discontinued. During the first year of treatment, exenatide, in combination with metformin and repaglinide, led to a weight loss of 14 kg and fat mass and waist circumference were respectively reduced from 31 to 25.5% and from 114 to 103 cm. Homeostatic model assessment (HOMA) was used to calculate ß-cell secretion which increased from 50 to 78% and insulin sensitivity which increased from 28 to 51%, reflecting a decrease in HbA(1c) by 1.9%. Exenatide may be a new therapeutic option for HIV-infected type 2 diabetes patients undergoing retroviral therapy.

One-year metabolic outcomes in patients with type 2 diabetes treated with exenatide in routine practice.

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.

Six-month exenatide improves HOMA hyperbolic product in type 2 diabetic patients mostly by enhancing beta-cell function rather than insulin sensitivity.

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.

Insulin detemir in routine clinical practice: a 26-week follow-up in type 1 diabetic patients from the Belgian PREDICTIVE Cohort.

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.