RESUMO
AIMS: LMNA-linked familial partial lipodystrophy type 2 (FPLD2) leads to insulin resistance-associated metabolic complications and cardiovascular diseases. We aimed to characterise the disease phenotype in a cohort of patients carrying an LMNA founder variant. METHODS: We collected clinical and biological data from patients carrying the monoallelic or biallelic LMNA p.(Thr655Asnfs*49) variant (n = 65 and 13, respectively) and 19 non-affected relative controls followed-up in Reunion Island Lipodystrophy Competence Centre, France. RESULTS: Two-thirds of patients with FPLD2 (n = 51) and one-third of controls (n = 6) displayed lipodystrophy and/or lean or android morphotype (P = 0.02). Although age and BMI were not statistically different between the two groups, the insulin resistance index (median HOMA-IR: 3.7 vs 1.5, P = 0.001), and the prevalence of diabetes, dyslipidaemia, and non-alcoholic fatty liver disease were much higher in patients with FPLD2 (51.3 vs 15.8%, 83.3 vs 42.1%, and 83.1 vs 33.3% (all P ≤ 0.01), respectively). Atherosclerosis tended to be more frequent in patients with FPLD2 (P = 0.07). Compared to heterozygous, homozygous patients displayed more severe lipoatrophy and metabolic alterations (lower BMI, fat mass, leptin and adiponectin, and higher triglycerides P ≤ 0.03) and tended to develop diabetes more frequently, and earlier (P = 0.09). Dilated cardiomyopathy and/or rhythm/conduction disturbances were the hallmark of the disease in homozygous patients, leading to death in four cases. CONCLUSIONS: The level of expression of the LMNA 'Reunionese' variant determines the severity of both lipoatrophy and metabolic complications. It also modulates the cardiac phenotype, from atherosclerosis to severe cardiomyopathy, highlighting the need for careful cardiac follow-up in affected patients.
Assuntos
Cardiomiopatias/genética , Lamina Tipo A/genética , Lipodistrofia Parcial Familiar/genética , Doenças Metabólicas/genética , Adulto , Cardiomiopatias/epidemiologia , Estudos de Casos e Controles , Feminino , Efeito Fundador , Frequência do Gene , Heterozigoto , Homozigoto , Humanos , Laminopatias/complicações , Laminopatias/epidemiologia , Laminopatias/genética , Lipodistrofia Parcial Familiar/complicações , Lipodistrofia Parcial Familiar/epidemiologia , Masculino , Doenças Metabólicas/epidemiologia , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Reunião/epidemiologia , Adulto JovemAssuntos
Androgênios/sangue , Tumor de Células da Granulosa/patologia , Hiperandrogenismo/etiologia , Neoplasias Ovarianas/patologia , Idoso , Feminino , Tumor de Células da Granulosa/sangue , Tumor de Células da Granulosa/complicações , Hirsutismo/etiologia , Humanos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/complicaçõesRESUMO
UNLABELLED: OBJECTIVE, METHOD: Chronic kidney disease is a major public health problem. This observational epidemiological study aimed to evaluate the prevalence of proteinuric nephropathy in patients with type 2 diabetes consulting a community-based general practitioner in French overseas departments and territories (DOM-TOM). Screening was carried out with reagent strips Albustix for proteinuria and, in case of trace amounts or a negative result, Microalbustix for microalbuminuria. RESULTS: 91 general practitioners participated in the study with 402 evaluable patients (54% female, mean age 60.1 +/- 11.2 years). The duration of diabetes was 8.9 +/- 6.6 years and mean HbA1c was 7.3 +/- 1.4% (52.2% with HbA1c < or = 7%). Screening was positive for 45.7% of the patients: 23.6% positive for proteinuria with Albustix [95% CI: 19.5-27.8] and 22.1% with Microalbustix. CONCLUSION: Screening with reagent strips revealed that nearly half the patients had proteinuria or albuminuria, thus confirming the high prevalence of nephropathy in type 2 diabetes patients living in the Dom-Tom and illustrating the need for frequent renal function screening in type 2 diabetics in general medicine for the prevention of chronic kidney disease.
