Endocrine Abstracts

Diabetes arising in young adulthood has a wide differential diagnosis, including autoimmune and genetic causes as well as young onset type 2 diabetes (YT2D). Specific features may be associated with each of these groups, but they cannot be differentiated from YT2D by mode of presentation. Family history, clinical characteristics and laboratory investigations provide complementary strategies to help dissect different known aetiologies.

We studied 268 UK Caucasians with apparent YT2D (diagnosed 18-45 years, not treated with permanent insulin for 6 months) and used a combination of clinical and laboratory testing to detect those with specific causes for diabetes.

On clinical assessment one subject was found to have familial partial lipodystrophy. 13 subjects who fulfilled traditional MODY diagnostic criteria (family member diagnosed <25 yrs, autosomal dominant inheritance) were excluded from the analysis.

Glutamic acid decarboxylase antibodies (GADA) indicating autoimmune diabetes were found in 23 (9%) subjects.

GADA -ve subjects were screened for common variants in the mitochondrial genome (A3243G) and Hepatocyte Nuclear Factor (HNF)-1alpha gene (P-291fsinsC). Lean subjects (BMI<28 kg/m²) or those with maternal history of diabetes were tested for A3243G. One subject was identified with classical maternally inherited diabetes and deafness. All subjects were screened for P-291 fsinsC, but no mutations were found.

Subjects were then selected for sequencing of the HNF-1alpha gene on the basis of absence of features of insulin resistance: BMI<28 kg/m², no dyslipidaemia and no hypertension. 2 out of 15 subjects had mutations: a novel missense mutation A501T, cosegregating with diabetes and the previously reported missense mutation R583Q.

In summary, 10% of subjects were found to have a defined aetiology, rising to 20% of lean subjects. Finding a specific aetiology will guide management and allow the risk to relatives to be estimated. We conclude that investigating young adults with apparent type 2 diabetes, particularly those with features of beta-cell dysfunction, is clinically worthwhile.