Influence of migration on characteristics of type 2 diabetes in sub-Saharan Africans.

AIM: This study compared the clinical and biochemical characteristics and microvascular complications found in three groups of type 2 diabetes (T2D) patients: Africans living in Africa; African immigrants living in France; and Caucasians living in France. METHODS: Diagnosed T2D Africans living in Cameroon (n=100) were compared with 98 African migrants diagnosed with T2D after having moved to France, and a group of 199 T2D Caucasian patients living in France. All underwent clinical and biochemical evaluations, and all were assessed for microvascular complications. RESULTS: The median duration of stay of the migrants in France was 15years before being diagnosed with diabetes. Despite similar durations of diagnosis, they were 8.9years younger at the time of diagnosis than Africans living in Cameroon (P<0.001). Caucasians and African immigrants in France had lower HbA1c values than Africans in Cameroon (P<0.001); they were also more aggressively treated for hypertension and dyslipidaemia and, therefore, had significantly lower blood pressure levels and better lipid profiles. Diabetic nephropathy and retinopathy rates were higher in Cameroon than in the two other groups. After adjusting for age, diabetes duration, HbA1c, hypertension and other covariates, only the prevalence of diabetic nephropathy (OR: 5.61, 95% CI: 2.32-13.53; P<0.0001) was higher in Cameroon compared with those living in France. CONCLUSION: Our results suggest that Africans who emigrate to France may develop diabetes earlier than those staying in their home country. However, the latter may be a reflection of late diagnosis of diabetes. Also, the less adequate diabetes and hypertension control in the latter would explain their higher rates of nephropathy. Large-scale cohorts are now warranted to substantiate these observations.

[Propositions for the standardized expression of HbA 1c results]. / Propositions pour l'expression standardisée des résultats d'HbA 1c.

The 2007 international consensus about the standardization of HbA(1c) determination and expression of results is progressively implemented in most countries. In France, a common working group of the Société française de biologie clinique (SFBC) and the Société francophone de diabétologie (SFD) has expressed the following recommendations. HbA(1c) results are expressed in percentage of total hemoglobin and in mmol HbA(1c)/mol Hb, but are not converted into estimated average glucose. A table indicating the correspondence between HbA(1c) and estimated average glucose may be given with the results, subject to precautions of interpretation at the individual level.

Mesenchymal stem cells: Stem cell therapy perspectives for type 1 diabetes.

Mesenchymal stem cells (MSCs) are multipotent non-haematopoietic progenitor cells that are being explored as a promising new treatment for tissue regeneration. Although their immunomodulatory properties are not yet completely understood, their low immunogenic potential together with their effects on immune response make them a promising therapeutic tool for severe refractory autoimmune diseases. Type 1 diabetes is characterized by T cell-mediated autoimmune destruction of pancreatic beta cells. While insulin replacement represents the current therapy for type 1 diabetes, its metabolic control remains difficult, as exogenous insulin cannot exactly mimic the physiology of insulin secretion. Pancreatic or islet transplantation can provide exogenous insulin independence, but is limited by its intrinsic complications and the scarcity of organ donors. In this context, stem cell therapy, based on the generation of insulin-producing cells (IPCs) derived from MSCs, represents an attractive possibility. In this review, we provide a brief characterization of MSC immunomodulatory effects, and present the current experimental evidence for the potential therapeutic efficacy of MSC transplantation in diabetes.

The polymorphism Arg585Gln in the gene of the sterol regulatory element binding protein-1 (SREBP-1) is not a determinant of ketosis prone type 2 diabetes (KPD) in Africans.

AIM: Ketosis prone type 2 diabetes (KPD) is an atypical form of diabetes described mainly in people of sub-Saharan African origin. Its pathogenesis is unknown, although we have previously described a high prevalence of glucose-6-phosphate-dehydrogenase (G6PD) deficiency in patients with KPD. However, 50% of these deficient patients lacked the G6PD gene mutation. The isoforms of the transcription factor sterol regulatory element binding protein 1 (SREBP-1) are known to stimulate G6PD gene expression, and some polymorphisms in the SREBP-1 gene (SREBF-1) have been described only in Africans. We investigated one of these, the Arg585Gln polymorphism, in a candidate gene approach for KPD. METHODS: We examined the presence of the Arg585Gln polymorphism in SREBF-1 in 217 consecutive unrelated Africans [73 patients with KPD, 80 with classical type 2 diabetes (T2D) and 64 nondiabetic subjects]. Patients underwent clinical and biochemical evaluations, and were assessed for G6PD activity and insulin secretion (glucagon test). RESULTS: There were no differences in frequency of the Arg585Gln polymorphism and the 585Gln allele among the three groups (allele frequency: KPD: 0.089, T2D: 0.031, nondiabetic group: 0.070; P=0.1). When the 585Gln allele frequency was compared separately between patients with KPD and those with T2D, it was significantly higher in the former (P=0.032). There was no difference between carriers and noncarriers of the 585Gln allele regarding G6PD activity and insulin secretion. CONCLUSION: The results of this exploratory study show that the polymorphism Arg585Gln in SREBF-1 is not associated with the KPD phenotype. Further studies in larger populations are needed to confirm our findings.

Hypoglycaemia in patients with type 2 diabetes treated with a combination of metformin and sulphonylurea therapy in France.

CONTEXT: Hypoglycaemia from antihyperglycaemic drugs may have a significant impact on patients' health-related quality of life. Combination use of metformin and a sulphonylurea has become increasingly common; yet, the impact of hypoglycaemia on quality of life in these patients is not well documented. OBJECTIVE: To examine patient-reported experience of hypoglycaemia, worry about hypoglycaemic symptoms and the impact of hypoglycaemia on patients' quality of life associated with use of sulphonylurea co-administered with metformin. DESIGN: This was an observational, cross-sectional, multi-centre study. SETTING: A total of 98 primary care centres in France during October to December 2005. PATIENTS: A total of 400 patients with type 2 diabetes, who were > or = 35 years old and who had been treated with metformin and a sulphonylurea for at least 6 months, completed questionnaires during their usual primary care office visit. MAIN OUTCOME MEASURES: Frequency and severity of hypoglycaemic symptoms in the past 6 months, the Worry subscale of the Hypoglycaemic Fear Survey-II (HFS-II) and the EuroQol-5 Dimensions (EQ-5D) questionnaire. RESULTS: A total of 136 (34%) patients reported experiencing hypoglycaemia, of whom 78 (58%) experienced mild, 40 (30%) experienced moderate and 16 (12%) experienced severe or very severe symptoms. Mean score on the HFS-II Worry scale was higher for patients who reported having hypoglycaemia than for those who did not (19.0 vs. 10.2; p < 0.0001) and increased with severity of hypoglycaemic symptoms. In linear regression analyses, more severe symptoms of hypoglycaemia were significantly associated with higher scores on the HFS-II Worry scale (p = 0.0162) among patients with hypoglycaemic symptoms. Summary scores on the EQ-5D were lower for patients who reported hypoglycaemia than for those who did not (p = 0.0001) and, in multivariate analysis, the experience of hypoglycaemia was negatively associated with the EQ-5D summary score (p < 0.0001). CONCLUSION: The occurrence and severity of hypoglycaemic symptoms were associated with increased patient worry about hypoglycaemia and lower health-related quality of life among type 2 diabetic patients being treated with both metformin and a sulphonylurea.

Gender and neurogenin3 influence the pathogenesis of ketosis-prone diabetes.

Ketosis-prone diabetes (KPD) is a phenotypically defined form of diabetes characterized by male predominance and severe insulin deficiency. Neurogenin3 (NGN3) is a proendocrine gene, which is essential for the fate of pancreatic beta cells. Mice lacking ngn3 develop early insulin-deficient diabetes. Thus, we hypothesized that gender and variants in NGN3 could predispose to KPD. We have studied clinical and metabolic parameters according to gender in patients with KPD (n = 152) and common type 2 diabetes (T2DM) (n = 167). We have sequenced NGN3 in KPD patients and screened gene variants in T2DM and controls (n = 232). In KPD, male gender was associated with a more pronounced decrease in beta-cell insulin secretory reserve, assessed by fasting C-peptide [mean (ng/ml) +/- s.d., M: 1.1 +/- 0.6, F: 1.5 +/- 0.9; p = 0.02] and glucagon-stimulated C-peptide [mean (ng/ml) +/- s.d., M: 2.2 +/- 1.1, F: 3.1 +/- 1.7; p = 0.03]. The rare affected females were in an anovulatory state. We found two new variants in the promoter [-3812T/C (af: 2%) and -3642T/C (af: 1%)], two new coding variants [S171T (af: 1%) and A185S (af: 1%)] and the variant already described [S199F (af: 69%)]. These variants were not associated with diabetes. Clinical investigation revealed an association between 199F and hyperglycaemia assessed by glycated haemoglobin [HbA1c (%, +/-s.d.) S199: 12.6 +/- 1.6, S199F: 12.4 +/- 1.4 and 199F: 14.1 +/- 2.2; p = 0.01]. In vitro, the P171T, A185S and S199F variants did not reveal major functional alteration in the activation of NGN3 target genes. In conclusion, male gender, anovulatory state in females and NGN3 variations may influence the pathogenesis of KPD in West Africans. This has therapeutic implications for potential tailored pharmacological intervention in this population.

An unusual somatotropin and thyreotropin secreting pituitary adenoma efficiently controlled by Octreotide and Pegvisomant.

We describe the first case of a 36 year-old male patient with a somatotropin and thyreotropin secreting pituitary adenoma, co-treated by a long-acting releasing somatostatin analog (Octreotide) and a GH receptor antagonist (Pegvisomant). The patient normalized his biological disease activity reflected by hormone levels but his tumor size remained unchanged as measured by MRI. The co-treatment was well tolerated and induced a synergic effect on IGF1 levels that allowed us to use low doses of both therapies.

Hyperglycaemia acutely decreases circulating dehydroepiandrosterone levels in healthy men.

OBJECTIVE: This study was conducted in order to evaluate the effect of glucose-insulin homeostasis on adrenal steroids and was designed to separate the effects of hyperglycaemia from those of insulin. DESIGN: Eight healthy men aged 22.6 +/- 3.4 (SD) underwent an 80 mU/m2/min hyperinsulinaemic euglycaemic 100-min clamp, a 200-min graded glucose infusion at 2-16 mg/kg/min and a measurement of fat mass. MEASUREMENTS: Circulating glucose, insulin and adrenal steroid levels including dehydroepiandrosterone (DHEA) were determined before and during both infusion tests. Steroid variations in relation to insulinaemia and glycaemia were analysed using univariate, multivariate tests and nonlinear mixed models. RESULTS: Hyperinsulinaemia induced no significant modification of adrenal steroid levels. By contrast, hyperglycaemia decreased all adrenal steroids except DHEA-sulphate by 47-66%. The drop occurred early, averaging 51% for 17OH pregnenolone and 57% for DHEA at the 80th minute of glucose infusion, whereas blood glucose was 7.1 +/- 1.2 mmol/1. This effect was independent of insulinaemia, fat mass and waist circumference. Thus, we estimated models that could best predict steroid variations according to blood glucose. At thresholds defining impaired fasting glycaemia and diabetes, the estimated decrease in DHEA was 40% and 45%, respectively, culminating at 60% at 9.3 mmol/1 glycaemia, with no detectable further decrease. CONCLUSIONS: Our data suggest that hyperglycaemia dramatically decreases adrenal androgen levels in men, possibly by acting at early steps of synthesis, independently of insulinaemia and fat mass.

Absence of exercise-induced variations in adiponectin levels despite decreased abdominal adiposity and improved insulin sensitivity in type 2 diabetic men.

OBJECTIVE: We investigated the effect of an intensive training program on fasting leptin and adiponectin levels. METHODS: Sixteen middle-aged men with type 2 diabetes were randomly assigned to either a training or control group. The training program consisted of 8 weeks of supervised endurance exercise (75% VO(2peak), 45 min) twice a week, with intermittent exercise (five 2 min exercises at 85% VO(2peak) separated by 3 min exercises at 50% VO(2peak)) once a week, on an ergocycle. RESULTS: Training decreased abdominal fat by 44%, increased mid-thigh muscle cross-sectional area by 24%, and improved insulin sensitivity by 58% without significant change in body weight. Compared with controls, no significant variation in leptin or adiponectin levels was observed. However, in the trained group, change in adiponectin correlated with change in body weight (Spearman rank correlation, r(s):-0.76, P=0.03) but not with insulin sensitivity or abdominal adiposity variations. CONCLUSIONS: An 8 week intensive training program inducing a marked reduction in abdominal fat and increase in insulin sensitivity does not affect adiponectin and leptin levels in men with type 2 diabetes.

Adrenal insufficiency and diabetes mellitus secondary to the use of topical corticosteroids for cosmetic purpose.

We report a case of symptomatic topical corticosteroid-induced adrenal insufficiency and diabetes in a 46-yr old HIV 1 positive woman of African descent. Topical Betamethasone dipropionate 0.05%-containing creams were used for the purpose of bleaching over a 2 month period prior to the acute episode. She recovered from her acute onset diabetes with ketosis and adrenal insufficiency a few months after withdrawal of corticosteroids. Despite possible discussion about pathophysiology of diabetes because acute-onset remitting diabetes is not rare in patients of African descent, and diabetes may occur in patients taking anti-retroviral treatments, no other cause of a hypothalamo-pituitary-adrenal axis disorder was found. This case suggests that chronic use of high dose topical corticosteroid containing creams should be ruled out in patients presenting with Hypothalamo-Pituitary-Adrenal hypofunction.

Marital status and family size of type 1 diabetic patients in a French cohort.

OBJECTIVE: To compare the marital status, the number of offspring and the cumulative incidence of type 1 diabetes in offspring of type 1 diabetic men and women. METHODS: From the database of patients attending our department, we reviewed the files of all the 352 subjects aged >=40 years with type 1 diabetes and compared male and female patients for whom age, age at diagnosis of diabetes, marital status, socio-economic status, number and age of offspring, diagnosed type 1 diabetes in the offspring could be obtained from patient's record and/or direct interview (86 males and 78 females). RESULTS: In this population, 73% of women and 81% of men were married or living a marital life (NS), and 35% of women versus 8% of men had no offspring (P<0.0001). The proportion of parents with 2 offspring or more was 43% in females and 61% in males (p=0.03) and was not related to the socio-economic status. The number of offspring with diagnosed type 1 diabetes was small (8/229) and did not show significant association with gender of the parent, with a cumulative incidence of 3.2 and 3.7% in offspring of type 1 diabetic mothers and fathers respectively. CONCLUSION: Type 1 diabetic women born before 1960 had fewer children than men. In this cohort, there was no difference in the cumulative incidence of type 1 diabetes in offspring of type 1 diabetic men and women despite reduced family size in women.

Metabolic and immunogenetic prediction of long-term insulin remission in African patients with atypical diabetes.

AIMS: We aimed to characterize a cohort of 'atypical' diabetic patients of sub-Saharan African origin and to analyse possible determinants of long-term remission. METHODS: Over 6 years, we studied the clinical and therapeutic profile of 42 consecutive patients undiagnosed or untreated prior to inclusion presenting with cardinal features of diabetes mellitus. We measured insulin secretion and sensitivity at inclusion. Immunogenetic (anti-GAD, anti-ICA and HLA class II) markers of Type 1 diabetes were compared with a 90-non-diabetic unrelated adult African population. RESULTS: Twenty-one ketonuric patients (age 42 +/- 9 (sd) years; body mass index (BMI) 26 +/- 3 kg/m2) were initially insulin-treated (IT), and 21 non-ketonuric patients (age 38 +/- 8 years; BMI 26 +/- 5 kg/m2) had oral and/or diet therapy (NIT). Insulin could be discontinued in 47.6% (10/21) IT with adequate glycaemic control (HbA1c 6.7 +/- 1.3%), while insulin was secondarily started in 38.1% (8/21) NIT in expectation of better control. The initial basal (odds ratio (OR) 9.1, 95% confidence interval (CI) 1.3-64.4) and stimulated C-peptide (OR 8.17, 95% CI 1.5-44.1) were independently associated with remission. Insulin resistance was present in all the groups, more marked in the insulin-treated NIT. Anti-GAD antibodies and ICA were rare, but 38.1% IT vs. 1.1% controls had Type 1 diabetes HLA susceptibility haplotypes (P < 0.001) without significant difference between the subgroups. CONCLUSION: Prolonged discontinuation of insulin is frequent in African diabetic patients initially presenting with signs of insulinopenia. In our patients, long-term insulin therapy was not associated with immunogenetic markers of Type 1 diabetes. The initial measure of insulin secretion seemed a good predictor of long-term remission.

Effects of minoxidil 2% vs. cyproterone acetate treatment on female androgenetic alopecia: a controlled, 12-month randomized trial.

BACKGROUND: Hormone studies have demonstrated the androgen-dependent character of female androgenetic alopecia, but there have been few controlled studies of therapies for alopecia in women. OBJECTIVES: To compare topical minoxidil 2% and cyproterone acetate in the treatment of female alopecia. METHODS: Sixty-six women with female-pattern alopecia were randomly assigned for 12 cycles into two groups, 33 received two local applications (2 mL day-1) of topical minoxidil 2% plus combined oral contraceptive and 33 received cyproterone acetate 52 mg day-1 plus ethinyl oestradiol 35 microg for 20 of every 28 days. RESULTS: A mean reduction of 2.4 +/- 6.2 per 0.36 cm2 in hairs of diameter > 40 microm was observed in the cyproterone acetate group (P = 0.05) and a mean increase of 6.5 +/- 9 per 0.36 cm2 in the minoxidil group (P < 0.001). Comparison of the total number of hairs at 12 months and the body mass index (BMI) revealed a borderline positive correlation in the cyproterone acetate group (r = 0.39, P = 0.06) and a negative correlation in the minoxidil group (r = -0.42, P < 0.05). No significant difference was observed in the total number of hairs among cyproterone acetate patients according to the presence or absence of other symptoms of hyperandrogenism, whereas in the minoxidil group, the total number of new hairs was higher in patients with isolated alopecia (Delta = 8.1; P < 0.05). Variations in scalp seborrhoea were significant in both groups, but the result was better (for acne and hirsutism as well) in the cyproterone acetate group than in the minoxidil group (P < 0.001). CONCLUSIONS: Minoxidil treatment was more effective in the absence of other signs of hyperandrogenism, hyperseborrhoea, and menstrual cycle modifications when the BMI was low, and when nothing argued in favour of biochemical hyperandrogenism. Cyproterone acetate treatment was more effective when other signs were present and when the BMI was elevated, factors that favoured a diagnosis of biochemical hyperandrogenism.

[Acne in adult women: data from a national study on the relationship between type of acne and markers of clinical hyperandrogenism]. / Acné de la femme adulte.

INTRODUCTION: The role of hyperandrogenism in acne occurring or persisting in adult women is controversial. Studies reported have often been carried out in hospital settings. The aim of this nationwide prospective and descriptive study was to evaluate the frequency of clinical hyperandrogenism in a large number of adult acneic women visiting dermatologists in a non-hospital setting. PATIENTS AND METHODS: Three hundred and fifteen dermatologists completed clinical questionnaires concerning the next five female patients with acne at their private practices. These patients had to be between 25 and 45 years of age. The questionnaire covered patients' demographic characteristics, medical history, gynaecological status and acne history. Patients' acne, seborrhea and cycle disorders were described, as well as other signs suggesting hyperandrogenism, such as hirsutism and alopecia. RESULTS: A total of 1 135 questionnaires were analyzed. Nearly 50 p. 100 of the patients had major scalp or facial seborrhea, 18.4 p. 100 hirsutism, 7 p. 100 alopecia and 32.2 p. 100 menstrual cycle abnormalities. When these signs were present, acne was more often retentional, with more scarring and more widespread. CONCLUSION: This prospective study in a large number of patients in a non-hospital setting shows that acne in adult women is frequently associated with clinical hyperandrogenism.

Diabetes in Africans. Part 2: Ketosis-prone atypical diabetes mellitus.

Diabetes is increasing with ageing and changes in lifestyle in populations of African ancestry as described in the first part of this review. Apart from classical type 1 and Type 2 diabetes, atypical presentations are observed in these populations, especially "tropical" and "ketosis-prone" atypical diabetes. Ketosis-prone atypical diabetes that has been classified by ADA as idiopathic Type 1 diabetes or Type 1b is the most common atypical form. It is characterised by an acute initial presentation with severe hyperglycaemia and ketosis, as classical Type 1 diabetes. In the subsequent clinical course after initiation of insulin therapy, prolonged remission is often possible with cessation of insulin therapy and maintenance of appropriate metabolic control. Metabolic studies showed a markedly blunted insulin secretory response to glucose, partially reversible with the improvement of blood glucose control. Variable levels of insulin resistance are observed, especially in obese patients. Pancreatic B-cell autoimmunity is an exceptional finding. Association with type 1 susceptibility HLA alleles is variable. The molecular mechanisms underlining the insulin secretory dysfunction are still to be understood and may involve gluco-lipotoxicity processes, glucagon dysregulation, effect of stress, or may be genetically determined. The present review summarises the available clinical and metabolic features and suggests some pathogenetic hypotheses and principles of management for the ketosis-prone atypical diabetes of the Africans.

[Feminine acne: dermatologic disease or endocrine disease?]. / Acné féminine: maladie dermatologique ou maladie endocrinienne?

Acne is a problem of the pilo-sebaceous follicle caused by the conjunction of three factors: seborrhea, follicle obstruction, and follicle inflammation. The key element, seborrhea, is under androgenic control. Acne in women is also influenced by developments and modifications in genital life, as well as by hormonal contraceptive and replacement therapies. Acne is rare prior to puberty, when it may indicate endocrine disease. At puberty, acne is quasi-physiological, because of the relative hyperandrogenism induced by the andrenarche preceding pubarche, as well as by the relative shortage of estrogens and progesterone during the first menstrual cycles. Other signs of hyperandrogenism, such as menstrual cycle difficulties and excess weight, which favor a hormonal origin, must be sought in cases of persistent or late-onset acne in adults. There is a mirror image of puberty during the peri-menopausal period, but with decreased seborrhea, so acne is rare. Finally, a tumoral origin must be sought in the rare cases of acne occurring after menopause. Hormonal investigation of acne should not be systematic, but is justified during prepuberty when other symptoms are associated with acne that resists well-conducted dermatological treatment. The therapeutic approach should be primarily dermatological, but hormone-oriented treatment should be considered when such therapy fails, or in the presence of other signs of hyperandrogenism. Sometimes the association of isotretinoin and an anti-androgen treatment are necessary to effectively treat such acne. Finally, particular attention must be paid to contraceptive therapies and hormone treatments, which can induce or aggravate acne, especially during the peri-menopausal period.

Prolonged immune deficiency following allogeneic stem cell transplantation: risk factors and complications in adult patients.

To evaluate the long-term immune reconstitution after allogeneic haematopoietic stem cell transplantation (SCT), we prospectively screened standard immune parameters in a series of 105 patients, at a median time of 15 months after SCT. Analysing lymphoid phenotypes, in vitro immune functions and immunoglobulin levels, we found that, more than 1 year post SCT, cellular and humoral immunity was still altered in a significant number of patients. CD4+ T cells were < 200/microl in one third of patients, and the CD4/CD8 ratio was still reversed in 78% of patients. Almost all patients showed positive T-cell responses against mitogens, but antigen-specific proliferation assays identified 20% to 80% of non-responders. B-cell counts were reconstituted in 61% of the patients, but levels of total immunoglobulins were still low in 59%. In multivariate analyses, human leucocyte antigen (HLA) disparity between donor and recipient and chronic graft-versus-host disease were the leading causes affecting immune reconstitution. Interestingly, cytomegalovirus (CMV) infections were strongly associated with normal CD8+ T-cell counts. Studying the impact of impaired immune reconstitution on the rate of infections occurring in the 6 years following screening, we identified three parameters (low B-cell count, inverted CD4/CD8 ratio, and negative response to tetanus toxin) as significant risk factors for developing such late infections.