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.

The effect of vildagliptin relative to sulphonylureas in Muslim patients with type 2 diabetes fasting during Ramadan: the VIRTUE study.

AIMS: To assess, in a real-world setting, the effect of vildagliptin compared with sulphonylurea (SU) treatment on hypoglycaemia in Muslim patients with type 2 diabetes mellitus (T2DM) fasting during Ramadan. METHODS: This multinational, non-interventional study, conducted in Asia and the Middle East, included Muslim adult patients with T2DM who received treatment with vildagliptin or SU as add-on to metformin or monotherapy. During a ~16-week observation period, data were collected up to 6 weeks before and 6 weeks after Ramadan fasting. The primary study objective was to compare the proportion of patients with ≥ 1 hypoglycaemic event (HE) during fasting. RESULTS: Of > 1300 patients enrolled in the study, 684 were treated with vildagliptin and 631 with SUs. Significantly fewer patients experienced ≥ 1 HE with vildagliptin compared with those receiving SUs (5.4% vs. 19.8%, respectively; p < 0.001); no vildagliptin-treated patients reported a grade 2 HE, vs. 4 SU-treated patients (p = 0.053). Mean HbA1c changes from baseline were vildagliptin: -0.24%, SUs: +0.02% (p < 0.001). Mean body weight reductions from baseline were vildagliptin: -0.76 kg, SUs: -0.13 kg (p < 0.001). A higher proportion of SU-treated patients experienced adverse events (AEs) compared with vildagliptin (22.8% vs. 10.2%). This difference was driven by hypoglycaemia as the most common AE. CONCLUSIONS: In this real-world study of fasting Muslim patients with T2DM, vildagliptin was associated with significantly fewer hypoglycaemic episodes compared with SU therapy. This outcome is particularly meaningful when viewed in the context of good glycaemic and weight control observed in vildagliptin-treated patients. Vildagliptin was well tolerated in this patient population.

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.

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.

Insulin-like growth factor system abnormalities in hepatitis C-associated osteosclerosis. Potential insights into increasing bone mass in adults.

Hepatitis C-associated osteosclerosis (HCAO) is a rare disorder characterized by a marked increase in bone mass during adult life. Despite the rarity of HCAO, understanding the mediator(s) of the skeletal disease is of great interest. The IGFs-I and -II have potent anabolic effects on bone, and alterations in the IGFs and/or IGF-binding proteins (IGFBPs) could be responsible for the increase in bone formation in this disorder. Thus, we assayed sera from seven cases of HCAO for IGF-I, IGF-II, IGF-IIE (an IGF-II precursor), and IGFBPs. The distribution of the serum IGFs and IGFBPs between their ternary ( approximately 150 kD) and binary (approximately 50 kD) complexes was also determined to assess IGF bioavailability. HCAO patients had normal serum levels of IGF-I and -II, but had markedly elevated levels of IGF-IIE. Of the IGFBPs, an increase in IGFBP-2 was unique to these patients and was not found in control hepatitis C or hepatitis B patients. IGF-I and -II in sera from patients with HCAO were carried, as in the case of sera from control subjects, bound to IGFBP-3 in the approximately 150-kD complex, which is retained in the circulation. However, IGF-IIE was predominantly in the approximately 50-kD complex in association with IGFBP-2; this complex can cross the capillary barrier and access target tissues. In vitro, we found that IGF-II enhanced by over threefold IGFBP-2 binding to extracellular matrix produced by human osteoblasts and that in an extracellular matrix-rich environment, the IGF-II/IGFBP-2 complex was as effective as IGF-II alone in stimulating human osteoblast proliferation. Thus, IGFBP-2 may facilitate the targeting of IGFs, and in particular IGF-IIE, to skeletal tissue in HCAO patients, with a subsequent stimulation by IGFs of osteoblast function. Our findings in HCAO suggest a possible means to increase bone mass in patients with osteoporosis.

Clinical application of the two-layer (University of Wisconsin solution/perfluorochemical plus O2) method of pancreas preservation before transplantation.

BACKGROUND: The two-layer method [University of Wisconson solution (UW)/perfluorochemical plus O2] for pancreas preservation has been demonstrated to be superior to simple UW storage alone in the canine model. For the first time, we applied the two-layer method to clinical whole-pancreas transplantation. METHODS: Pancreases were placed in the two-layer method in 10 cases and UW alone in 44 cases before transplant. The mean cold ischemic time was 16.5 hr in the two-layer group versus 18.1 hr in the UW group (P=NS). We compared the condition of graft at the time of reperfusion, and then 3 months posttransplant graft function and complications. RESULTS: At the time of reperfusion, no grafts in the two-layer group were edematous, compared with 10(23.3%) of 43 in the UW group (P=0.18). Seven (70%) of 10 grafts in the two-layer group obtained the best overall quality score, compared with 24(57.1%) of 42 in the UW group (P=0.72). Nine (90%) of 10 recipients in the two-layer group became insulin-independent during hospitalization, compared with 31(70.5%) of 44 in the UW group (P=0.26). Time to insulin independence was no different between the two groups. No pancreas grafts preserved by the two-layer method suffered acute rejection. Conclusions. The two-layer preservation method is feasible in human clinical transplantation. It was at least equivalent and may be superior to UW alone in both morphologic and functional assessment of the transplanted pancreas.

Glycated hemoglobin in insulinoma.

OBJECTIVE: To determine whether preoperative levels of glycated hemoglobin (GHb) are lower in patients with functioning insulinoma and, if so, whether a distinct separation of GHb values from those in control subjects might serve for diagnosis. METHODS: We examined preoperative GHb in consecutive patients (who had this measurement done) with surgically confirmed insulinoma for the period 1983 (when the current method became available for routine use) through 1996. Hemoglobin A(1) (HbA(1)) was measured by the Isolab Glyc-Affin Test System (normal range, 4 to 7%). We studied 64 patients with insulinoma (40 women and 24 men; median age, 47.5 years; age range, 21 to 79) and 38 control subjects (25 women and 13 men; median age, 42.5 years; age range, 20 to 83) considered not to have a hypoglycemic disorder on the basis of normal results of a supervised 72-hour fast. RESULTS: HbA(1) was significantly lower in patients with insulinoma (median, 4.7%; range, 2.7 to 6.9%) than in control subjects (median, 5.3%; range, 4.1 to 6.4%) (P<0.001, two-tailed rank sum test). Among 15 patients with insulinoma treated with diazoxide preoperatively, HbA(1) was higher (median, 4.8%; range, 4.2 to 6.9%) than in patients not treated with diazoxide (median, 4.6%; range, 2.7 to 5.7%), although the difference was not statistically significant (P = 0.08). CONCLUSION: Because of considerable overlap in HbA(1) values, no GHb value was diagnostic for insulinoma; however, 16 of 64 patients (25%) with insulinoma had HbA(1) values below the lowest value (4.1%) in control subjects. Thus, HbA(1) values less than 4.1% in patients with possible insulinoma are strongly indicative of that disorder.

Insular thyroid carcinoma in adolescents: a potentially lethal endocrine malignancy.

BACKGROUND: Insular thyroid carcinoma is intermediate in aggressiveness between well differentiated and anaplastic thyroid carcinomas. METHODS: The authors describe two children with insular thyroid carcinoma who had markedly different outcomes. In the first case, a girl age 15 years, 2 months presented with a large pulsatile mass in the right thyroid lobe. In the second case, a girl age 16 years, 3 months presented after total thyroidectomy was performed elsewhere for confirmed pTNM Stage I insular thyroid carcinoma. RESULTS: In Case 1, total thyroidectomy was performed, and histologic examination revealed insular thyroid carcinoma with lymph node involvement. Six weeks postoperatively, neck masses reappeared. There was significant radioactive iodine uptake in the thyroid bed and in a palpable right supraclavicular lymph node; this was associated with an increased serum thyroglobulin level. Ultrasound-guided biopsy of the lymph node confirmed recurrent insular carcinoma, and neck dissection was performed. Six weeks later, there was 0.35% iodine uptake in the neck, and the patient was treated with 300 mCi of (131)I. She had no signs of recurrence when last seen 22 months postoperatively. In Case 2, the patient was given 29.9 mCi of (131)I for remnant ablation. Four months postoperatively, fine-needle aspiration biopsy of a high jugular lymph node demonstrated recurrence. The patient was given 200 mCi of (131)I but had no significant response. Right modified neck dissection was performed, followed by external beam radiation. Despite aggressive treatment with a further 500 mCi of (131)I, progressive lung and mediastinal metastases developed, followed by brain metastasis. The patient died 31 months after the initial diagnosis. CONCLUSIONS: Insular thyroid carcinoma may occur and behave aggressively in children. Vigorous initial surgical and radioactive iodine treatments are warranted.