Mody 2

MODY is the acronym for "Maturity-onset Diabetes of the Young" and describes a group of autosomal-dominantly inherited, genetically heterogeneous, not always insulin-dependent forms of diabetes. The MODY forms of diabetes are caused by various disorders of beta cell function in the pancreas. The body weight of MODY patients is usually normal. Neither are any of the autoimmune phenomena characteristic of type 1 diabetes observed. Rare are other associated organ dysplasias (eyes, pancreas, intestine).

In MODY2, the second most common form of MODY, the gene for the enzyme glucokinase is mutated. As a result, the measurement function for glucose concentration is disturbed and insulin release from beta cells is delayed. MODY 2 patients show persistent, mild hyperglycaemia (Gregory JM et al. 2019). MODY type 2 is often only discovered by chance during routine diagnostics, e.g. during screening examinations in pregnancy or in the case of impaired glucose tolerance.

Mody 2 is caused by >40 previously known mutations in the glucokinase gene (GCK) (Aykut A et al. 2018). The different genotypes are all characterized by an identical phenotype (Liu L et al. 2018).

According to a larger study on 99 MODY 2 patients, no typical diabetic late complications of the heart, vessels or kidneys occur. The only consequence of lifelong MODY hyperglycaemia is an increased rate of retinopathies, which are, however, significantly less pronounced than in type 2 diabetics (Steele AM et al.2014).

MODY2 does not usually require medication (see MODY2 and pregnancy). In this respect, the course of the diabetes can be described as mild. It is stable over years. An adapted diet and physical activity is sufficient for non-pregnant women (Dickens LT et al. 2019).

1. Aykut A et al (2018) Analysis of the GCK gene in 79 MODY type 2 patients: A multicenter Turkish study, mutation profile and description of twenty novel mutations. Genes 641:186-189.
2. Delvecchio M et al (2017) Diabetes Study Group of the Italian Society of Pediatric Endocrinology and Diabetes (ISPED). Monogenic Diabetes Accounts for 6.3% of Cases Referred to 15 Italian Pediatric Diabetes Centers During 2007 to 2012 J Clin Endocrinol Metab 102:1826-1834.
3. Gregory JM et al (2019) Iatrogenic Hyperinsulinemia, Not Hyperglycemia, Drives Insulin Resistance in Type 1 Diabetes as Revealed by Comparison to GCK-MODY (MODY2). Diabetes. doi: 10.2337/db19-0324.
4. Hosokawa Y et al (2019) Pregnancy outcome of Japanese patients with glucokinase-maturity-onset diabetes of the young. J Diabetes Investig doi: 10.1111/jdi.13046.

5. Liu L et al (2018) Insights into pathogenesis of five novel GCK mutations identified in Chinese MODY patients. metabolism. J metabolism 89:8-17. doi: 10.1016/j.metabol.2018.09.004.

6. Steele AM et al(2014) Prevalence of vascular complications among patients with glucokinase mutations and prolonged, mild hyperglycemia. JAMA 311:279-286.