medwireNews : Mutations in HNF1A and HNF4A are less likely to be associated with a diagnosis of maturity-onset diabetes of the young (MODY) when discovered incidentally versus in a clinically selected cohort, research suggests.

To investigate its potential for treating GK-MODY, Chow and colleagues carried out a small exploratory study including eight GK-MODY patients and 10 newly diagnosed type 2 diabetes patients.

He added MODY3 accounts for about 70% of all MODY cases.

Adding linagliptin to glimepiride treatment reduces some measures of glycemic variability and improves glycemic control in patients with HNF1A-MODY, indicate findings from the GLIMLINA trial.

Marcus and team found that the key discriminatory clinical feature of MODY was negativity to all four islet autoantibodies, which occurred in 100% of people with MODY versus 11% of those without known MODY.

The authors also report that eight of nine individuals with GCK -MODY stopped all diabetes medication following their genetic diagnosis.

The rate of MODY among these 469 patients was 4.1% when restricted to those carrying variants that were likely or definitely pathogenic.

The researchers initially recruited 24 participants, but two proved to have type 1 diabetes and two maturity-onset diabetes of the young (MODY), leaving 20 people – 13 women and seven men.

Jay Shubrook, Chair of the American Diabetes Association’s Primary Care Advisory Group, outlines what's new in 2018's ADA Standards of Care update. 

Most common types of MODY MODY-1 Familial, and early onset Responds well to SU MODY-2 Second most common form of MODY Can be present at birth or diagnosed early Glucokinase defect Can respond to dietary modification A low carbohydrate diet and not eating carbohydrates first can help MODY-3 Most common form of MODY Hepatocyte nuclear factor-1 defect Responds well to SU Low-dose SU works and maybe also sodium-glucose co-transporter-2 inhibitors MODY-5 Early diabetes plus often cystic kidney disease MODY-8 Exocrine pancreatic insufficiency MODY=monogenic diabetes of youth While there have been few developments in recent years, a recent study published in Nature has found a new genetic mutation that leads to a novel form of MODY [3].

Table 6 [2.7 in SOC 2017] - Most common causes of monogenic diabetes Gene Inheritance Clinical features MODY   GCK AD GCK-MODY: stable, nonprogressive elevated fasting blood glucose; typically does not require treatment; microvascular complications are rare; small rise in 2-h PG level on OGTT (<54 mg/dL [3 mmol/L]) HNF1A AD HNF1A-MODY: progressive insulin secretory defect with presentation in adolescence or early adulthood; lowered renal threshold for glucosuria; large rise in 2-h PG level on OGTT (>90 mg/dL [5 mmol/L]); sensitive to sulfonylureas HNF4A AD HNF4A-MODY: progressive insulin secretory defect with presentation in adolescence or early adulthood; may have large birth weight and transient neonatal hypoglycemia; sensitive to sulfonylureas HNF1B AD HNF1B-MODY: developmental renal disease (typically cystic); genitourinary abnormalities; atrophy of the pancreas; hyperuricemia; gout Neonatal diabetes   KCNJ11 AD Permanent or transient: IUGR; possible developmental delay and seizures; responsive to sulfonylureas INS AD Permanent: IUGR; insulin requiring ABCC8 AD Transient or permanent: IUGR; rarely developmental delay; responsive to sulfonylureas 6q24 ( PLAGL1, HYMA1 ) AD for paternal duplications Transient: IUGR; macroglossia; umbilical hernia; mechanisms include UPD6, paternal duplication or maternal methylation defect; may be treatable with medications other than insulin GATA6 AD Permanent: pancreatic hypoplasia; cardiac malformations; pancreatic exocrine insufficiency; insulin requiring EIF2AK3 AR Permanent: Wolcott-Rallison syndrome: epiphyseal dysplasia; pancreatic exocrine insufficiency; insulin requiring FOXP3 x-linked Permanent: immunodysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome: autoimmune diabetes; autoimmune thyroid disease; exfoliative dermatitis; insulin requiring 6.    

Seventy patients had C-peptide levels of 200–600 pmol/L and included 39 with positive autoantibodies, two of whom also had MODY mutations.

Monogenic diabetes, including maturity-onset diabetes of young (MODY) and type 1 diabetes, are also characterized by family association.

In keeping with other studies from Russia, the majority of MODY mutations were in the GCK gene, present in 34.0% of patients with overt GDM and 13.7% of those with milder GDM.