Efficacy and safety of liraglutide compared to sulphonylurea during Ramadan in patients with type 2 diabetes (LIRA-Ramadan): a randomized trial.

AIMS: Compare effects of liraglutide 1.8 mg and sulphonylurea, both combined with metformin, on glycaemic control in patients with type 2 diabetes (T2D) fasting during Ramadan. MATERIALS AND METHODS: In this up to 33-week, open-label, active-controlled, parallel-group trial, adults [glycated haemoglobin (HbA1c) 7%-10% (53-86 mmol/mol); body mass index ≥20 kg/m(2) ; intent to fast] were randomized (1:1) ≥10 weeks before Ramadan to either switch to once-daily liraglutide (final dose 1.8 mg) or continue pre-trial sulphonylurea at maximum tolerated dose, both with metformin. PRIMARY ENDPOINT: change in fructosamine, a validated marker of short-term glycaemic control, during Ramadan. RESULTS: Similar reductions in fructosamine levels were observed for both groups during Ramadan [liraglutide (-12.8 µmol/L); sulphonylurea (-16.4 µmol/L); estimated treatment difference (ETD) 3.51 µmol/L (95% CI: -5.26; 12.28); p = 0.43], despite lower fructosamine levels in the liraglutide group at start of Ramadan. Fewer documented symptomatic hypoglycaemic episodes were reported in liraglutide-treated (2%, three subjects) versus sulphonylurea-treated patients (11%, 18 subjects). No severe hypoglycaemic episodes were reported by either group. Body weight decreased more during Ramadan with liraglutide (ETD: -0.54 kg; 95% CI: -0.94;-0.14; p = 0.0091). The proportion of patients reporting adverse events was similar between groups. Liraglutide led to greater HbA1c reduction [ETD: -0.59% (-6.40 mmol/mol), 95% CI: -0.79; -0.38%; -8.63; -4.17 mmol/mol; p < 0.0001]. CONCLUSIONS: Despite lower fructosamine levels and body weight at the beginning of Ramadan, use of liraglutide showed similar glycaemic improvements, fewer hypoglycaemic episodes and greater body weight reduction compared with sulphonylurea. LIRA-Ramadan provides evidence for liraglutide being safe and efficacious for management of T2D during Ramadan fasting.

The Safety and Benefit of Statins in Liver Cirrhosis: a Review.

Dyslipidemia is a primary, major risk factor for coronary artery disease CAD. The prevalence of dyslipidemia had decreased over the past 30 years, which may in part be explained by the steady increase in the use of lipid-lowering drug therapy, especially statins. Cardiovascular risk has been shown to be greater in liver disease (20% in the liver cirrhosis vs. 12% in the general population), where statins can play an important role as a primary and secondary prevention for CAD. Given patients with chronic liver disease, especially liver cirrhosis are at risk of decreased hepatic clearance, there is concern that this patient population may be at higher risk for complications from statin therapy. Several retrospective studies showed that statin use in chronic liver disease and cirrhosis is safe, and even it was associated with lower mortality and lower rate of hepatic decompensation. This review discusses the safety and the different mechanisms where statins can decrease the rate of complications in liver cirrhosis, including portal hypertension, sepsis and the incidence of hepatocellular carcinoma.

Barriers to the delivery of optimal antidiabetic therapy in the Middle East and Africa.

BACKGROUND: The prevalence of type 2 diabetes is increasing worldwide, but developing nations will bear a disproportionate share of this burden. Countries in the Middle East and Africa are in a state of transition, where marked disparities of income and access to education and healthcare exist, and where the relatively young populations are being exposed increasingly to processes of urbanisation and adverse changes in diet that are fuelling the diabetes epidemic. Optimising diabetes care in these nations is crucial, to minimise the future burden of complications of diabetes. METHODS: We have reviewed the barriers to effective diabetes care with special relevance to countries in this region. RESULTS: The effects of antidiabetic treatments themselves are unlikely to differ importantly in the region compared with elsewhere, but economic inequalities within countries restrict access to newer treatments, in particular. Values relating to family life and religion are important modifiers of the physician-patient interaction. Also, a lack of understanding of diabetes and its treatments by both physicians and patients requires more and better diabetes education, delivered by suitably qualified health educators. Finally, sub-optimal processes for delivery of care have contributed to a lack of proper provision of testing and follow-up of patients in many countries. CONCLUSION: Important barriers to the delivery of optimal diabetes care exist in the Middle East and Africa.

Barriers to the delivery of diabetes care in the Middle East and South Africa: a survey of 1,082 practising physicians in five countries.

AIMS: Developing countries face a high and growing burden of type 2 diabetes. We surveyed physicians in a diverse range of countries in the Middle East and Africa (Egypt, Kingdom of Saudi Arabia, United Arab Emirates, South Africa and Lebanon) with regard to their perceptions of barriers to type 2 diabetes care identified as potentially important in the literature and by the authors. METHODS: One thousand and eighty-two physicians completed a questionnaire developed by the authors. RESULTS: Most physicians enrolled in the study employed guideline-driven care; 80-100% of physicians prescribed metformin (with lifestyle intervention, where there are no contraindications) for newly diagnosed type 2 diabetes, with lifestyle intervention alone used where metformin was not prescribed. Sulfonylureas were prescribed widely, consistent with the poor economic status of many patients. About one quarter of physicians were not undertaking any form of continuing medical education, and relatively low proportions of practices had their own diabetes educators, dieticians or diabetic foot specialists. Physicians identified the deficiencies of their patients (unhealthy lifestyles, lack of education and poor diet) as the most important barriers to optimal diabetes care. Low-treatment compliance was not ranked highly. Access to physicians did not appear to be a problem, as most patients were seen multiple times per year. CONCLUSIONS: Physicians in the Middle East and South Africa identified limitations relating to their patients as the main barrier to delivering care for diabetes, without giving high priority to issues relating to processes of care delivery. Further study would be needed to ascertain whether these findings reflect an unduly physician-centred view of their practice. More effective provision of services relating to the prevention of complications and improved lifestyles may be needed.

The effect of parental intellectual disability status on child protection service worker decision making.

BACKGROUND: There is evidence to suggest that parents with an intellectual disability (ID) constitute a higher proportion of child-protective services (CPS) cases than would be expected based on the prevalence of ID in the general population. Researchers have suggested that the stereotypic assumptions and expectations that CPS workers have about parents with an ID might influence decisions and responses made to such parents. This study examined whether parental ID (having an ID vs. not) had an effect on CPS workers' emotional reactions, attributions and decisions about risk to the child, whether to remove the child and workers' general willingness to help the parent. METHOD: Two hundred and twelve CPS workers read vignettes describing parents who were labelled as either having or not having an ID. Workers responded to the vignettes by making ratings of their emotional reactions, attributions and decisions regarding risk, removal and helping. RESULTS: CPS workers made significantly higher ratings of pity, willingness to help and risk for parents with an ID than for parents without an ID. Lower ratings of anger and disgust were found for parents with an ID than for parents without an ID. Parents' intellectual status did not have a direct effect on workers' attributions or removal decisions. CONCLUSIONS: The results show evidence for the influence of stereotypes regarding parental ID due to its differential effect on CPS workers' emotional reactions and decisions about child risk and their willingness to help.

Optimising the medical management of hyperglycaemia in type 2 diabetes in the Middle East: pivotal role of metformin.

AIMS: Increases in the prevalence of type 2 diabetes will likely be greater in the Middle East and other developing countries than in most other regions during the coming two decades, placing a heavy burden on regional healthcare resources. METHODOLOGY: Medline search, examination of data from major epidemiological studies in the Middle Eastern countries. RESULTS: The aetiology and pathophysiology of diabetes appears comparable in Middle Eastern and other populations. Lifestyle intervention is key to the management of diabetes in all type 2 diabetes patients, who should be encouraged strongly to diet and exercise. The options for pharmacologic therapy in the management of diabetes have increased recently, particularly the number of potential antidiabetic combinations. Metformin appears to be used less frequently to initiate antidiabetic therapy in the Middle East than in other countries. Available clinical evidence, supported by current guidelines, strongly favours the initiation of antidiabetic therapy with metformin in Middle Eastern type 2 diabetes patients, where no contraindications exist. This is due to its equivalent or greater efficacy relative to other oral antidiabetic treatments, its proven tolerability and safety profiles, its weight neutrality, the lack of clinically significant hypoglycaemia, the demonstration of cardiovascular protection for metformin relative to diet in the UK Prospective Diabetes Study and in observational studies, and its low cost. Additional treatments should be added to metformin and lifestyle intervention as diabetes progresses, until patients are receiving an intensive insulin regimen with or without additional oral agents. CONCLUSIONS: The current evidence base strongly favours the initiation of antidiabetic therapy with metformin, where no contraindications exist. However, metformin may be under-prescribed in the Middle East.

Biphasic insulin aspart 30 treatment improves glycaemic control in patients with type 2 diabetes in a clinical practice setting: experience from the PRESENT study.

AIM: The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study aims to assess the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes mellitus in routine clinical practice. METHODS: This was a 6-month, prospective, multinational, multiethnic observational study involving 21 977 patients from 13 countries (India, Iraq, Jordan, Kuwait, Lebanon, Qatar, Romania, Russia, Saudi Arabia, South Africa, South Korea, Turkey and the United Arab Emirates). The patients were transferred to BIAsp 30 with or without oral antidiabetic drugs (OADs) from prior treatment with OAD (n = 8583), insulin (n = 5942), OAD + insulin (n = 4673) or diet (i.e. treatment naive) (n = 1707). One thousand and seventy-two patients had incomplete or no information on previous treatment. RESULTS: At 3 and 6 months, significant reductions from baseline were observed in the mean haemoglobin A(1c) (HbA(1c)) (-1.33 and -1.81%), fasting plasma glucose (-3.02 and -3.74 mmol/l) and postprandial plasma glucose (-4.76 and -5.82 mmol/l) (p < 0.001). A significantly greater proportion of patients achieved target HbA(1c) of less than 7% at 3 months (15.3%) and 6 months (27.7%) compared with baseline (4.8%) (p < 0.001). Overall, the mean HbA(1c) at 6 months was lowered in patients regardless of prior treatment: -2.15% (OAD), -1.45% (insulin), -1.47% (OAD + insulin) and -2.35% (treatment naive). In the overall cohort, the rate of total hypoglycaemia was reduced from 5.4 events per patient-year at baseline to 2.2 events per patient-year at study end (p < 0.001). Among prior treatment subgroups, the rates of total hypoglycaemia were reduced from 2.5 to 2.1 events per patient-year in the OAD group, from 9.6 to 2.2 events per patient-year in the insulin group and from 7.6 to 2.5 events per patient-year in the OAD + insulin group but were increased from 1.0 to 1.8 events per patient-year in the treatment-naive group (p < 0.001). There were 444 adverse drug reactions (ADRs), including 13 serious ADRs: lipodystrophy (three events), symptoms of generalized hypersensitivity (two events), acute painful neuropathy (one event), worsening of diabetic retinopathy (one event), oedema (one event) and unspecified ADRs (five events). CONCLUSION: The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was effective and safe in patients with poorly controlled type 2 diabetes mellitus.

Biphasic insulin aspart 30 treatment in patients with type 2 diabetes poorly controlled on prior diabetes treatment: results from the PRESENT study.

AIM: The safety and efficacy of biphasic insulin aspart (BIAsp30) were evaluated in patients uncontrolled on previous treatment (human insulin +/- oral hypoglycaemic agent [OHA] or OHA only) in routine clinical practice. METHODS: This was a large, multi-national, multicentre, prospective, 6-month study in type 2 diabetes mellitus patients who were prescribed BIAsp30. Changes in glycated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), proportion who achieved target HbA(1c) < 7% and rate of hypoglycaemic episodes were assessed. This paper evaluates outcomes in patients by diabetes duration (< 5, 5-10, 10-20 or >/= 20 years) stratified by prior therapy. RESULTS: After 6 months of treatment, glycaemia improved significantly across the duration subgroups. The improvement was better in insulin-naïve group versus prior insulin group: HbA(1c) decreased approximately 2.2%-points versus approximately 1.6%-points, FPG decreased approximately 4.5 mmol/L versus approximately 2.9 mmol/L and PPPG decreased approximately 6.8 mmol/L versus approximately 5.0 mmol/L. Target HbA(1c) was achieved by about one in four patients although insulin-naïve patients achieved this at comparatively lower BIAsp30 dose. Body weight remained relatively unchanged. Hypoglycaemic episodes appeared to be more frequent in the prior insulin group which decreased during the treatment period. CONCLUSIONS: According to this observational study, in clinical practice, initiating or transferring uncontrolled patients to biphasic insulin aspart improved glycaemic control without using a strict insulin algorithm.

Transferring type 2 diabetes patients with uncontrolled glycaemia from biphasic human insulin to biphasic insulin aspart 30: experiences from the PRESENT study.

AIM: The Physician's Routine Evaluation of Safety and Efficacy of NovoMix* 30 Therapy (PRESENT) aims to assess the safety and efficacy of biphasic insulin aspart (BIAsp30) used in routine clinical practice. METHODS: This was a large, multi-national, multi-centre, prospective, 6-month study in type 2 diabetes mellitus patients who were prescribed BIAsp30. Efficacy endpoints included changes in HbA(1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), and proportion who achieved target HbA(1c) < 7%. Changes from baseline were analysed using paired t-test. Safety endpoints were incidence and rate of hypoglycaemic episodes. A subgroup of patients previously uncontrolled (HbA(1c) > or = 7.0%) on biphasic human insulin (BHI) were analysed. RESULTS: Glycaemia improved significantly (mean +/- SD): HbA(1c) by 1.58 +/- 1.69% points (from 9.32 +/- 1.64% to 7.70 +/- 1.29%), FPG by 2.92 +/- 3.71 mmol/L and PPPG by 4.75 +/- 4.87 mmol/L. The incidence of hypoglycaemic episodes decreased over time, from 38.7% (baseline) to 20.8% (6 months). Episodes were mostly minor (reduced from 37.7 to 20.6% at 6 months), occurring during the day (reduced from 31.5 to 17.1% at 6 months). Major episodes were less frequently reported (reduced from 5.0 to 0.4% at 6 months). The rate of hypoglycaemia (episodes/patient year) from baseline to end of study decreased over time for overall (8.9-2.2), major (0.7-0.1), minor (8.2-2.2) and nocturnal (2.9-0.5) episodes. CONCLUSIONS: In this observational study, in the type 2 diabetes mellitus patients who were poorly controlled on BHI, glycaemia improved when transferred to BIAsp30, and a lower incidence or rate of hypoglycaemia was observed in these patients.

Insulin therapy during Ramadan fast for Type 1 diabetes patients.

Patients with Type 1 diabetes (T1D) are normally exempt from the Ramadan fast; however, some patients insist on following the fast, often without the approval of their physicians. The aim of this study is to provide patients with T1D, who insist on fasting, with the most appropriate insulin regimen during the month of Ramadan. Seventeen patients with T1D who insisted on fasting were studied. Prior to Ramadan, the intermediate insulin was changed to ultralente in all patients. The total dose of insulin given to fasting patients by the end of Ramadan (45.7 +/- 14.4 U/day) was less than the total dose of insulin given before fasting (52.8 +/- 13.1 U/day) p<0.05. The ultralente and regular insulin constituted 70 and 30%, respectively, of the total insulin dose by the end of Ramadan, divided equally between Suhur (before sunrise) and Iftar (after sunset). There was no change in the glycosylated hemoglobin before and after fasting. Patients were instructed to break their fast after any episode of hypoglycemia. There were no severe daytime hypoglycemia episodes. We recommend that patients with T1D wishing to fast be switched to long acting insulin such as ultralente. The total insulin dose should consist of around 85% of their initial insulin dose and it should be composed of around 70% ultralente and 30% rapid insulin, divided equally between Suhur and Iftar.

Host and environmental factors defining the epidemiology of type 1 diabetes mellitus in a group of Lebanese children and young adults.

The effect of a number of host and environmental factors on the onset of type 1 diabetes mellitus (DM1) in a group of Lebanese children and young adults was studied. Results showed that DM1 in a group of 253 patients presented no gender preference and that the age of onset was similar in both genders. The overall body mass index reflected good metabolic control. HbA1c had a mean value of 8.98%, suggesting poor glucose control. Family history of DM1 and type 2 diabetes mellitus as well as consanguinity in patients' families were not different from those reported in the literature. Finally, onset of DM1 showed seasonal variation, peaking during winter months. DM1 showed a higher prevalence of onset among children born first and a decreased incidence as birth order increased. This study provides valuable data for the diagnosis, control and prevention of DM1 in children.

Leptin levels in patients with type 1 diabetes receiving intensive insulin therapy compared with those in patients receiving conventional insulin therapy.

Several reports suggest that insulin may have a role in the regulation of serum leptin levels, and this is related to the fact that serum leptin levels generally indicate the amount of body fat. Studies show that leptin levels are low in newly diagnosed patients with Type-1 diabetes (T1 DM) and increase after institution of insulin therapy. This study was designed to test whether serum leptin levels are higher in patients receiving intensive insulin therapy (IIT) compared to conventional insulin therapy (CIT). Young patients with T1 DM were studied, 23 on IIT and 23 on CIT. The patients were matched for age (19+/-3 and 20+/-5 yr, respectively), duration of diabetes (8+/-5 and 10+/-6 yr, respectively) and BMI (24+/-4 and 23+/-3 kg/m2, respectively). Leptin levels were higher in IIT compared to CIT (13+/-12 vs 7+/-7 ng/ml, respectively, p<0.05). The results of this study demonstrate that patients on IIT have higher leptin levels than patients on CIT. This increase in leptin level in IIT patients is independent of changes in bw and is probably due to the stimulatory effect of insulin on leptin production.

Type-2 diabetes family history delays the onset of type-1 diabetes.

Type-1 diabetes (T1D) is an autoimmune disease leading to insulin deficiency. Its occurrence is influenced by genetic and environmental factors. The human leukocyte antigen (HLA) region on chromosome 6 accounts for 45% of the genetic susceptibility for the disease, mainly the HLA-DQB1*0201 and HLA-DQB1*0302 alleles. Among the environmental factors involved, early exposure to cow's milk seems to be a trigger. In this study, we investigated the occurrence of T1D in 253 Lebanese Caucasian patients, in relation to HLA-DQB1*0201, HLA-DQB1*0302, HLA-DQB1*0602, gender, and early exposure to cow's milk, as well as to family history of T1D and type-2 diabetes (T2D). Our genetic analysis results show that in the patients studied, 77% and 40% were positive for BQ1*0201 and BQ1*0302, respectively. As for BQ1*0602, only 0.8% of patients were positive for this T1D protective allele, compared with 24% among the controls. Furthermore, our results did not show any gender preference of the disease or any effects of early intake of cow's milk on the age at onset of T1D. When family history of T2D or T1D was studied, our results show a novel finding whereby an immediate family history of T2D, but not T1D, delays the age at onset of T1D.

Improved pituitary function after V-P shunt insertion in pseudotumor cerebri.

Pseudotumor Cerebri is a disease of cerebrospinal fluid pressure regulation. This disease has also been associated with endocrine disorders like Cushing's syndrome, hypoparathyroidism, hypothyroidism, hyperthyroidism and Addison's disease. In this paper we report a 30-year-old male patient with hypoparathyroidism presenting with pseudotumor cerebri and diminished anterior pituitary function that improved after a ventricular-peritoneal (VP) shunt insertion.

The DD genotype of the ACE gene polymorphism is associated with diabetic nephropathy in the type-1 diabetics.

Genetic factors are involved in the development of diabetic nephropathy in type-1 diabetes. We are examining the association of the angiotensin-converting enzyme (ACE), insertion/deletion (I/D) polymorphism with the presence of diabetic nephropathy in type-1 diabetic patients. 52 type-1 diabetic patients with diabetic nephropathy (30 with either microalbuminuria or macroalbuminuria and 22 with end stage renal disease on dialysis) were compared with 10 type-1 diabetic patients with normoalbuminuria and duration of disease longer than 15 years and 27 non-diabetic healthy subjects. We found that the D-allele frequency was higher in patients with nephropathy than in the healthy and normoalbuminuric controls. There was an association in the DD polymorphism of the ACE gene with patients with diabetic nephropathy and not with the control subjects. We conclude that the DD genotype of ACE gene polymorphism is associated with diabetic nephropathy in patients with type-1 diabetes mellitus.

Characterization of insulin-resistance: role of receptor alteration in insulin-dependent diabetes mellitus, essential hypertension and cardiac hypertrophy.

Insulin-resistance is associated with a number of disease states such as diabetes, syndrome X, and hypertension. These situations may be coupled to insulin-resistance through the insulin signaling system as a common pathway. The purpose of this study was to investigate the receptor binding alterations in streptozotocin-induced diabetic rats, spontaneously hypertensive rats and aortocaval shunted rats (eccentric cardiac hypertrophy). A physical model describing a 1:1 stoichiometry of ligand binding with its receptor is proposed describing reversible binding of [(125)I]insulin or [(125)I]IGF-1 at the microvascular endothelial as well as with the cardiac myocytes after CHAPS-treatment. Analysis of the collected effluents are curve-fitted with a conservation equation and a first-order Bessel function which allowed the calculation of the forward binding constants (k(n)), the reversible constants (k(-n)), the dissociation constants (k(d)) and the residency time constants (tau). The results showed that streptozotocin-induced diabetic rats showed insulin-resistance through alterations in the kinetics of insulin receptor binding. The normotensive controls of the spontaneously hypertension rats (SHR) carry themselves insulin-resistant receptors whose binding to insulin worsens in the hypertensive SHR. Negative cooperativity between insulin-like growth factor IGF-1 and insulin receptors could be a causative factor predisposing for insulin-resistance in the aortocaval shunted rats to insulin resistance. The defects may be occurring at the receptor level in insulin-dependent diabetes mellitus, Wistar-Kyoto rats and spontaneously hypertensive rats. In conclusion, alterations in the kinetics of insulin binding to its receptor seem to play a central role for the initiation of insulin-resistance during the various pathophysiological states.

Preventing burnout in professionals and paraprofessionals who work with child abuse and neglect cases: a cognitive behavioral approach to supervision.

Professionals and paraprofessionals who treat children and families where child maltreatment has occurred are subject to many strains. This article focuses on the potential for burnout in such work. It discusses strategies in supervision to combat early manifestations of burnout and to prevent its full-blown occurrence. A cognitive-behavioral framework is used to help supervisors identify the sources of strain, the maladaptive, and inflexible assumptions regarding their own capacities as professionals and their own views of families that these strains may violate, and ways to work with supervisees to reduce the impact these violations have. It also addresses supervisors' own reactions to the high level of needs such families and children present and the strain on the supervisory relationship they produce. Institutionally based and systemic issues are highlighted.