Chronic diabetic complications in patients with MODY3 diabetes

Abstract

MODY3 diabetes, which is caused by a mutation in the hepatocyte nuclear factor-1alpha gene (HNF-1alpha) on chromosome 12, represents a relatively common monogenic form of diabetes in Finland. Age at onset of the disease can vary from 10 to 60 years, but little is known about the natural course of the disease, particularly the development of diabetes-related chronic complications. The availability of genetic markers now allows description of the clinical course of the disease. In order to examine the prevalence of chronic diabetic complications in MODY3, we examined 57 carriers with HNF-1alpha mutations for the presence of micro- and macrovascular complications. Thirty-four percent of the MODY patients had mild and 13% had severe non-proliferative or proliferative retinopathy; this figure did not differ from the figures in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients matched for duration and glycaemic control but not for age. Neither did the prevalence of microalbuminuria differ between MODY3 and IDDM or NIDDM patients (19 vs 24 and 23%). Neuropathy was observed with the same frequency as previously reported in IDDM. Hypertension was less frequent in MODY3 and IDDM than in NIDDM (24.5 and 19 vs 53.7%; p < 0.001). Coronary heart disease was more common in MODY3 than in IDDM (16 vs 4.5%; p < 0.02) but less common than in the older NIDDM patients (33.3%; p < 0.02). In a multiple logistic regression analysis, poor glycaemic control was an independent risk factor for retinopathy (p = 0.03), microalbuminuria (p < 0.04) and neuropathy (p = 0.03). In conclusion, microangiopathic complications are observed with the same frequency in patients with MODY3 diabetes as in IDDM and NIDDM and are strongly related to poor glycaemic control.

Genetic and clinical characteristics of maturity-onset diabetes of the young in Chinese patients

“…These results were in agreement with those reported in other populations. 22,23 On the other hand, over half of the MODYX subjects were overweight, compared to only 24% in the MODY3 subjects. Furthermore, the higher BMI and triglyceride, lower HDL and a higher prevalence of hypertension in MODYX subjects suggested the presence of greater insulin resistance compared to the MODY3 subjects.…”

Genetic testing for maturity onset diabetes of the young: uptake, attitudes and comparison with hereditary non-polyposis colorectal cancer

“…The benefits of correct diagnosis include the possibility to individualise treatment to avoid hypoglycaemia, to recognise the risk in the family and commencement of early treatment with insulin during pregnancy to avoid foetal problems. Although MODY3 has been considered a mild form of diabetes, it can lead to severe microvascular complications depending mainly on the HbA1c level during lifetime [21]. Of note, the glucose tolerance deteriorates in most cases already during the pubertal years [20,22,23], although the diagnosis is often made much later.…”

Maturity Onset Diabetes of the Young 5

“…As complicações microvasculares, particularmente as que envolvem a retina e o rim, são tão comuns nestes doentes como nos restantes diabéticos, sendo por isso, provavelmente, determinadas pelo grau de controlo glicémico. (49) Estudos realizados em pré-diabéticos portadores de mutações em HNF1a e HNF4a demonstraram a deficiente função da célula  como a principal causa de diabetes nestes indivíduos, sem perda de sensibilidade à insulina. (50)(51)(52) É possível distinguir os portadores de HNF1a mutado de HNF4a mutado.…”