Prevalence of the missense mutation Gly574Ser in the hepatocyte nuclear factor-1alpha in Africans with diabetes.

BACKGROUND: Clinical presentation and natural history of diabetes are somewhat different in Black Africans compared to Caucasians. This peculiar disease course could be at least partly related to a specific genetic profile that has not been studied in this population. METHODS: Medical backgrounds, anthropometric and biologic parameters were obtained from 69 diabetic subjects in Dakar, Senegal, in 1998. Blood anti GAD and Islet Cell Antibodies were studied, using RIA and immunofluorescence assay. The HNF-1alpha gene was sequenced searching the Gly574Ser mutation, previously described in MODY 3. RESULTS: Among these 69 diabetic patients, 11 (16%) were found to have the G574S mutation affecting the HNF-1alpha. These 11 patients carrying the mutation were compared respectively with the 58 non carriers. Mean age (57.5 yr. +/- 11 vs 51.1 yr. +/- 15) and duration of diabetes (11.9 vs 6.7 yr), were similar in the two groups. BMI was not different in patients with the mutation (26.3 vs 23.3, p=0.06). Metabolic control (Glycosylated hemoglobin) was poor in the two groups (9.5% vs 9.2%). Chronic complications were equally found in the patients, but no mutation carrier had macroangiopathy. None of the anti GAD positive or ICA positive patients had the mutation. CONCLUSIONS: The HNF-1alpha Gly574Ser mutation was found in 16% of cases in a 69 diabetic patients group in Senegal. Diabetes was as severe as in non carriers of mutation. This mutation has been implicated in atypical diabetes of Afro-American children. The study confirms its prevalence in Africans with diabetes.

[Release of Loa loa antigens after treatment with ivermectin]. / Libération d'antigènes de Loa loa après traitement par l'ivermectine.

This study concerns 112 patients of whom 104 were followed up. Microfilaricidal treatment of loaiasis is sometimes followed by severe adverse reactions. Using an immunodiffusion technique and the measure of microfilaraemia by calibrated thick smear, the authors show that the intensity of adverse reactions is proportional to the quantity of microfilariae eliminated by the treatment. The appearance of Loa loa antigens within three days following treatment was evident in 83% of the subjects. Five patients presenting the serious adverse reactions described belonged to this group. However, the precise cause of these adverse reactions, allergic or toxic, has not been demonstrated.

[Hereditary xanthinuria, rare cause of hypo-uric acidemia. 2 cases]. / La xanthinurie héréditaire, cause rare d'hypo-uricémie. 2 observations.

BACKGROUND: Hypouricemia can be observed in uncommon situations as in our two patients with hereditary xanthinuria. CASE REPORTS: In the first case, hereditary xanthinuria was discovered in a 36-year-old man when routine tests revealed hypouricemia. In the second case, a 76-year-old woman, hypouricemia was also a fortuitous discovery. She had major xanthinuria and a radiotranslucid lithiasis in the right kidney. DISCUSSION: Hereditary xanthinuria is characterized by hypouricemia, low urinary urate excretion and increased concentration of xanthine and to a lesser extent hypoxanthine. The disease results from a defect in xanthine oxidase and is considered to be transmitted by autosomal recessive heredity. This rare metabolic disorder is more often asymptomatic and detected by routine chemistry. Development of xanthine lithiasis is directly related to the low solubility of xanthine and is the main complication of the disease, occurring in 30-40% of patients. There is no effective treatment and the only useful measure is to prevent xanthine urolithiasis by maintaining urinary output above 2 l/day.

[Value of scintigraphy using meta-iodo-benzyl-guanidine (MIBG) in the investigation of cardiac autonomic neuropathy in diabetic patients. Comparison with Ewing tests]. / Apport de la scintigraphie à la méta-iodo-benzyl-guanidine (MIBG) dans l'exploration de la neuropathie végétative cardiaque du diabétique. Comparaison avec les tests d'ewing.

UNLABELLED: Cardiac autonomic neuropathy is a frequent complication of diabetes leading to resting tachycardia, postural hypotension, painless myocardial ischaemia, rhythm disturbances and sudden cardiac death. The aim of the study was to evaluate in a diabetic population the sensitivity of two exploration modes of autonomic neuropathy in diabetics: the Ewing tests which are, at present time, the reference method and the (123-I) meta-iodo-benzyl-guanidine (MIBG) single photon emission computed tomography (SPECT) which evaluates the cardiac sympathetic innervation. PATIENTS AND METHODS: 9 male insulin-dependent diabetes mellitus patients were studied. Mean age was 40.7 +/- 15 years and diabetes duration was 10.8 +/- 6 years. None had hypertension or macroangiography as demonstrated by patient's history, clinical examination, rest and exercise electrocardiography and ambulatory blood pressure monitoring. The complications observed were background retinopathy in 2 patients, incipient nephropathy in 3 and a peripheral neuropathy in 1 patient. Ewing tests, i.e. Valsalva maneuver, beat to beat heart rate variation during deep breathing and standing, blood pressure response to standing and to sustained handgrip, were performed. The results were considered as pathologic when the score was over 2. After injection of 10 mCi (123-I) MIBG, planar images were realized at times 1, 2 and 4 hours and SPECT images after 2 hours. The heart/mediastinum uptake ratio was calculated. RESULTS: We noted abnormalities of planar images in 3 patients, SPECT images in 1, and both in 1 patient. None was positive for Ewing tests. CONCLUSION: Although MIBG SPECT will explore only the sympathetic innervation, these preliminary findings suggest that this technique could be more sensitive for the evaluation of cardiac autonomic neuropathy. Nevertheless cost and lack of disponibility of this technique should limit its use.

Epidemiological aspects of diabetes in Cameroon: what is the role of tropical diabetes?

Diabetes is a worldwide public health problem made more acute in Africa by low socio-economic standards. Cases with an unusual clinical course are frequent and probably related to tropical diabetes, a syndrome that has not yet been precisely defined. This study reports the results of a prospective study carried out in Cameroon on 550 diabetic patients attending the Yaounde Central Hospital who were followed between December 1990 and July 1994. They were classified according to WHO criteria into 136 insulin-dependent diabetes mellitus (IDDM) (24.7%), 405 non-insulin- dependent diabetes mellitus (NIDDM) (73.7%) and 9 diabetes secondary to other diseases (1.6%). No cases of malnutrition-related diabetes mellitus (MRDM) were found, but 18 subjects were considered to have so-called "African diabetes". Investigation of the cohort showed epidemiological and clinical features markedly different from those of Caucasian diabetic subjects. The age of onset in IDDM occurred in all age groups, with a mean (+/- SD) close to that of NIDDM (40.9 +/- 4.8 years vs 49 +/- 10.9; P < 0.001). A clear male preponderance was found (M/F sex ratio = 1.63), as it has been reported in most studies from sub-Saharan Africa, in contrast with the slight female predominance noted in the Sahel and Saharan countries. An increased prevalence of young and non-obese NIDDM was also found. Seventy-nine NIDDM cases (19.5%) were detected in individuals under 40 years of age, including 31 with normal weight. Many atypical features were noted: IDDM in obese patients, NIDDM in ketotic subjects and patients with varying insulin requirements, all of which led to difficulties in classifying many diabetic patients according to current practices. All these uncommon features are concordant with the nature of tropical diabetes, including not only MRDM but also African diabetes which occurs in individuals older than MRDM patients who show no signs of malnutrition. Thus, tropical diabetes is apparently a syndrome with aetiological heterogeneity which requires further definition through clinical, genetic and immunological studies.

[Diabetes and travel]. / Diabète et voyages.

With the continuing expansion in international air travel, increasing numbers of diabetic patients consult physicians for advice before going abroad. Careful planning is required taking into account climatic and medical conditions at the destination. Diabetic travelers should pack an appropriate treatment kit and contract special insurance coverage for medical evacuation. Precautions are necessary to limit the effects of motion sickness and time differences on diabetes control and especially the risk of hypoglycemia. Special attention is needed to avoid digestive problems and prevent foot injuries which can lead to serious complications in diabetic patients. Diabetic patients cannot forget their health problem during vacation and must be especially cautious when traveling. However with proper training, the risks of foreign travel can be reduced to acceptable levels.

[Development of blood pressure level over a three years period in non-insulin dependent diabetic subjects according to their microalbuminuria]. / Evolution à trois ans du niveau tensionnel des diabétiques non insulino-dépendants en fonction de leur microalbuminurie.

UNLABELLED: The purpose of this study is to compare over a three year period blood pressure modifications of type 2 diabetic subjects who suffer of incipient nephropathy to those who remain unharmed of this complication. PATIENTS AND METHOD: This study population is composed of 83 normotensive (BP < 140/90 mmHg) type 2 diabetic patients not receiving cardio-vascular treatment and unharmed of nephropathy (microalbuminuria inferior to 30 mg/24 hours). An evaluation of the diabetes mellitus is undertaken at a three year interval (A0 and A3). These 83 subjects are distributed in two groups according to the 24 hours microalbuminuria rate at A3. In group I (n = 60), patients whose rate is lower than 30 mg/24 hours and in group II (n = 23), patients whose microalbuminuria is over 30 mg. For these two groups, the following elements are compared at A0 and A3: body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), serum creatinine, cholesterol and triglycerides. RESULTS: The two groups do not differ in age (57.1 +/- 12 vs 53.8 +/- 16.4 years), duration of diabetes mellitus (11.7 +/- 8.6 vs 13.3 +/- 10.4 years) or body mass index (25.9 +/- 3.8 vs 26.2 +/- 4 kg/m2). At the time of the initial evaluation at A0, none of the studied parameters shows a significant difference between the two populations. Comparison of statements undertaken at A3 shows that blood pressure of Group II patients is higher than in group I, but the difference is only significant for systolic blood pressure (132 +/- 12 vs 139 +/- 11 mmHg; p < 0.01). The balance of diabetes mellitus, serum creatinine and lipid levels do not differ between these two groups. The blood pressure level of Group I doesn't differ significantly at A0 and A3 (128 +/- 11 vs 132 +/- 12 mmHg for SBP; 77 +/- 9 vs 78 +/- 7 mmHg for DBP). On the contrary, patients who develop a nephropathy see their blood pressure increase, but only SBP has a significant risk (128 +/- 12 vs 139 +/- 11 mmHg; p < 0.01). Apparition of a microalbuminuria and increase of blood pressure of Group II are not accompanied by a significant variation of serum creatinine. CONCLUSION: This study shows that for normotensive type 2 diabetic patients the transition from normo to microalbuminuria is associated with increases in systollic blood pressure. This blood pressure modification occur early, contemporary of the apparition of microalbuminuria, but relationship of causality between this two factors remains to be specified.

[Prevalence of hypertension in a black African diabetic population]. / Prévalence de l'hypertension artérielle dans une population de diabétiques africains.

BACKGROUND: It has been established that hypertension prevalence rate was higher in American Blacks than Whites or Mexicans. And hypertension is more frequent in diabetics. The prevalence of hypertension among diabetic African Blacks is not well documented. METHODS: A total of 550 diabetic patients attending to Central Hospital of Yaounde (Cameroon) were followed between 1990 and 1994. The 1993 WHO criteria were used to define hypertension (systolic blood pressure (SBP) > or = 140 or diastolic blood pressure (DBP) > or = 90 mmHg. We also have considered as hypertensive patients being treated with an antihypertensive medication before inclusion. All quantitative data are given as means +/- SD. RESULTS: For the whole study population characteristics were: age (at inclusion): 54.2 +/- 12.8 yrs: sex distribution: 341 men for 209 women (sex ratio: 1.63:1); known duration of diabetes: 5.7 +/- 5.6 yrs; Body Mass Index (BMI): 24.4 +/- 4.8 kg/m2. They are dividing into 136 IDDM, 405 NIDDM and 9 other types. In normotensive patients, blood pressure levels were: SBP 117 +/- 11 and DBP 75 +/- 8 mmHg, while in hypertensive: SBP 156 +/- 23 and DBP 95 +/- 13 mmHg. The difference between normo and hypertensive diabetics was significant (p > or = 0.001). Characteristics of hypertensive group were: age: 57 +/- 11.2 yrs, sex repartition 229 men for 136 women (sex ratio: 1.68:1), BMI: 24.9 +/- 4.8 kg/m2, diabetes classification: 63 IDDM, 297 NIDDM and 5 other types. According to recent WHO criteria (140/90) 365 subjects/550 were found to have high blood pressure, giving an overall prevalence of hypertension of 66.4% in the study population. Using former WHO definition (160/95) the prevalence was 42.2%. There was no statistical difference for prevalence between male (67.2%) and female (65.1%). But the difference was strongly significant (p < 0.001) between IDDM (46.3%) and NIDDM (73.3%). DISCUSSION: Hypertension prevalence studies in Africa have shown varying results (2.5-30%), with higher rates in urban than rural population. In African studies hypertension prevalence rates in diabetes were reported in the range 13-44%. The result of the present study is very near the high limit of known data in Africa. CONCLUSION: Such a prevalence rate of 66.4% in this Cameroonian diabetic population appears to be high, particularly in patients with NIDDM. These considerations bring to light the question of sensitiveness of African Blacks to hypertension when exposed to high blood pressure risk factors such as inadequate food and diabetes.

A prevalence survey of diabetes in Mauritania.

OBJECTIVE: To perform an epidemiological study of the prevalence of diabetes in Mauritania, West Africa, with little data available on diabetes in West Africa. RESEARCH DESIGN AND METHODS: The study was performed with a representative sample of the Mauritanian population. A random selection of the study population (n = 744) was drawn by a cluster sampling method. Screening for diabetes was made by capillary blood glucose (CBG) measurement, using strips analyzed by reflectance meter. Criteria for the diagnosis of diabetes were those of the World Health Organization (WHO). RESULTS: The survey performed a screening of 744 subjects whose sex distribution was 307 men and 437 women. Their mean age was 34.6 +/- 15.2 years, and their mean BMI was 22.7 +/- 5.1 kg/m2, with a significant difference for BMI between men (20.0 +/- 2.9 kg/m2) and women (24.3 +/- 5.5 kg/m2). According to the study criteria, we found 14 diabetic patients (4 men, 10 women). The crude prevalence of diabetes was 1.88% (95% CI 0.90-2.86). The difference in prevalence by sex was 1.30% (95% CI 0.00-2.60) for men and 2.29% (95% CI 0.89-3.43) for women. For the truncated 30- to 64-year-old age-group, the crude prevalence was 2.84%; the age-adjusted prevalence for the same 30- to 64-year-old age-group, using the standardized age distribution of Segi (10), was 2.61%. CONCLUSIONS: With a crude prevalence of diabetes of 1.88% and an age-adjusted prevalence of 2.61%, Mauritania may be classified among the countries with a low prevalence of diabetes, a finding which is not surprising, considering the low level of development of this region of Africa.

[Prolactinoma and pregnancy. Six cases and review of the literature]. / Prolactinome et grossesse. Mise au point à propos de 6 observations.

Prolactinoma is the most frequent of secreting pituitary adenomas. It is often discovered among women of childbearing-age presenting an association of amenorrhea and galactorrhea. Data in the literature from large series indicate the current risks of interaction between prolactinoma and pregnancy. Risks have been overestimated in the past and it is now recognized that pregnancy can be allowed providing strict follow-up is assured. Dopaminergic drugs have no teratogenic side-effects and are known to allow tumoral control and recovery of fertility in the majority of cases. The use of these medications explains the reduction of indications for surgery. Microprolactinomas are highly influenced by pregnancy and can even lead to tumor retrogression. Macroprolactinomas give complications more often, and require a good tumor control and a rigorous follow-up.

[Diabetes in Cameroon. Classification difficulties in Africa]. / Etude du diabète au Cameroun. Les difficultés de classification en Afrique.

Diabetes is a major health problem in Africa where management is complicated by poor socioeconomic conditions. Atypical presentations of diabetes appear to be common in tropical countries although there is still little accurate data in this regard. We describe 550 diabetic patients treated in Cameroon between December 1990 and July 1994. According to WHO criteria 136 of these patients (24.7%) were classified as insulin-dependent (IDDM), 405 (73.5%) as non-insulin-dependent (NIDDM), and 9 as secondary diabetes (1.6%) related to other diseases. There were no cases of malnutrition-related diabetes but 18 patients (3%) met the criteria for "African diabetes" defined by Cuisinier-Raynal. Study of this cohort revealed several differences with diabetic populations in industrialized countries. Insulin-dependent diabetes was observed in all age groups with a mean age of onset 40.0 +/- 14.8 years which is close to the mean age of onset of non-insulin-dependent diabetes (49 +/- 10.9 years). The overall M/F sex ratio was 1.63 demonstrating a clear-cut male predominance. There was a high incidence of non-insulin-dependent diabetes in young, non-obese subjects. In many cases classification was difficult because insulin requirements fluctuated greatly. The incidence of obesity in non-insulin-dependent diabetic patients was lower than in industrialized countries. These findings suggest the existence of a tropical diabetes syndrome unrelated to malnutrition. Thus African diabetes appears to be another aspect of the disease which has a variety of heterogeneous etiologic features that cannot be classified on the basis of available data. The current WHO system does not take atypical African diabetes into account.

[Modification of hemorheological parameters in microvascular complications of diabetes]. / Modification des paramètres hemorhéologiques au cours des complications microangiopathiques du diabète.

The aim of the present study was to assess the possible modifications in the parameters of red cell aggregation and blood and plasma viscosity in 92 diabetic patients compared to 82 non diabetic control subjects. Based on the presence of microalbuminuria (> 30 mg/24 h) and/or retinopathy each group of diabetic patients was divided into two subgroups. This study shows increased red cell aggregation and blood viscosity among diabetic patients with microangiopathy. There was a very good correlation between fibrinogen level and the different rheological measurements. The results of this study confirm the importance of the blood rheology abnormalities observable in diabetes. These disorders increase peripheral vascular resistances and ischemia and therefore worsen diabetic nephropathy and retinopathy.

[Secondary effects of the treatment of hypermicrofilaremic loiasis using ivermectin]. / Effets secondaires du traitement de la loase hypermicrofilarémique par l'ivermectine.

In the last ten years ivermectin appeared an efficient and safe alternative to diethylcarbamazine which is known to induce severe adverse reactions in loiasis, including encephalitis. After these results, large scale ivermectin treatments against onchocerciasis were carried out in Central Africa where loiasis is also endemic; and seven cases of severe reaction were reported in Cameroon since 1991, during these mass ivermectin treatments. In order to study adverse reactions in patients harbouring high load of Loa loa microfilariae (mf), we realized careful hospital based treatment in 112 patients with more than 3,000 mf/ml (ml) blood. Patients received once 200 micrograms ivermectin per kilogram at day 0 (D0). Clinical examination was made daily during the four following days (D1 to D4). Blood and urine samples were analysed before treatment and at D1 and D3. Lumbar puncture was made at D1 for 39 patients with more than 10,000 mf/ml; at D3 for the 49 following patients without consideration for the level of parasitaemia, and at D0 and D3 for ten voluntary patients. For analysis the patients were distributed in 3 groups according to initial parasitaemia: the first group included 50% out of the patients, those whose parasitaemia was fewer than 15,000 mf/ml blood; the second group included 25% patients whose parasitaemia was between 15,000 and 30,000 mf/ml; the third group included the last 25% patients whose parasitaemia was higher than 30,000 mf per ml blood. Adverse reactions were observed in 71% out of the patients. Symptoms described were fever, pruritus, headache, arthralgia. Most symptoms appeared 24 to 36 hours after treatment. Temperature increased significantly in group 3. Microfilaraemia decreased by 85% in the 3 groups during the 4 days following treatment. C-reactive-protein increased dramatically after treatment in all patients (p < 10(-4)). Some patients presented blood in urine in three groups but haematuria reached 35% of patients in group 3. Proteinuria is noted among 33% of all patients but 20% in group 1 and 2 versus 70% in group 3. Loa loa mf were observed in urine of half the patients, but in low amounts (< 10 mf per 50 ml urine). In cerebro-spinal fluid (CSF), some mf appeared at D1 or D3 in people heavily infected with Loa loa, reaching 80% of the patients of group 3. LP made at D0 in ten patients with parasitaemia higher than 30,000 mf/ml blood confirmed that CSF was naturally microfilaria free before treatment. One patient presented severe troubles with fever, asthenia and conscience troubles beginning at D3, reactive coma at D4, renal impairment with transitory anuria; progressive improvement in 2 weeks and complete recovery at D22; he presented 102 mf/ml CSF at D6. The study confirmed that ivermectin treatment is generally well tolerated. Among people with high Loa loa parasitaemia the symptoms after treatment are frequent but mild. However severe cases with conscience troubles are possible, and may occur in about 1% of subjects with more than 3,000 mf/ml blood. Severity of adverse reactions was linked to level of parasitaemia before treatment. The critical parasitaemia level which could lead to expect serious adverse effects seems to be 30,000 ml/ml blood. These informations should induce carefulness to carry out large scale treatments against filariosis in endemic areas of Loa loa.