Definition Incidence, and Prevalence of Maturity Onset Diabetes of Young (MODY)

Maturity-onset diabetes of the young (MODY) refers to a category of monogenic impairments that contain a dominant and inherited type of diabetes which does not depend on insulin (Anik et.al. 2015, pg. 252). It mostly occurs in the adolescents and the youth before they reach twenty-five years. The population which is highly at risk consists of young people who are below twenty-years. The condition is viewed as a rare factor that results in diabetes whereby it is mostly mistaken for either the Type 1 diabetes or the Type 2 diabetes. It is also quite challenging to distinguish MODY from the two forms of diabetes. It results in the dysfunction of the b-cell. Its incidence accounts for about one percent for all forms of diabetes and hence rare. Diagnosis presents the need for providing adequate personalized care with respect to the genetic etiology in addition to enabling the prognostication among the family members (Anik et.al. 2015, pg. 252).

Pathogenesis and genetics in general, subgroups, clinical signs, diagnostic criteria, and treatment.

The genes associated with MODY include; HNF1A, GCK, and HNF4A. The mutations that interfere with the HNF1A gene are viewed as the most prevalent causes of MODY from a global perspective. The gene contains ten exons by which the mutations reduce the rate of the transportation of glucose and metabolism. Gardner and Tai (2012, pg. 102 ) state, These HNF1A mutations demonstrate a high penetrance, with 63% of carriers developing diabetes by 25 years of age, 79% by 35 years of age, and 96% by 55 years of age. The scholars further explain that the place of mutation determines the age at which diagnosis takes place. They state, those with mutations in the terminal exons (810) are diagnosed on average eight years earlier than those with mutations in exons 16, (Gardner & Tai 2012, pg. 102). The dysfunction of the b-cell is viewed to take place before the occurrence of diabetes in the mutation carriers present in the HNF1A gene (Gardner & Tai 2012, pg. 104). The mutation carriers in the HNF1A gene are viewed to contain an insulinogenic index which is quite low despite the bold glucose being in the expected range. The carriers also have a lower response to insulin in comparison to the non-mutation carriers which are also in the same category. Due to the progressive aspect of MODY, individuals with the HNF1A mutations are viewed to be at high risk of experiencing macrovascular and microvascular problems as the individuals suffering from Type 1 and Type 2 diabetes. The rate of hypertension is viewed to be at par with the Type 1 diabetes. The viewpoint is that MODY patients with HNF1A mutations have raised HDL-C levels which can be a distinguishing feature between Type 2 diabetes and MODY. For Type 2 diabetes the HDL-C levels are low. Mutations in the GCK gene also result in MODY whereby those with mutations which are heterozygous exhibit mild and stable hyperglycemia that demonstrate a bit of weakening with time. Gardner and Tai (2012, pg. 104) state, Patients are generally asymptomatic, and hyperglycemia is commonly discovered during routine screening, for example during pregnancy or through insurance medicals. The HNF4A mutations are viewed to be less prevalent when compared to monogenic diabetes caused by GCK and HNF1A mutations. The HNF4A mutations occur similarly as the HNF1A mutations whereby the b-cell dysfunction is progressive, and most patients acquire diabetes when they are twenty-five years of age. The subgroups of MODY are identified as per the genetic mutation (Gardner & Tai 2012, pg. 104). There exists the HNF1A-MODY, GCK-MODY, and HNF4A-MODY. The clinical signs associated with the condition include; insulin independence, the presence of diabetes in the family history, the lack of autoantibodies present in the pancreatic antigens, the production of endogenous insulin, and the absence of ketoacidosis during the omission of insulin after the diagnosis of diabetes. The features are viewed to be atypical for patients with Type 1 diabetes and therefore increasing the chances of the occurrence of MODY (Pihoker et.al. 2013, pg. 4060).

The diagnosis of MODY is affiliated with the type of mutation which also applies to the treatment. The treatment of HNF1A-MODY includes small intake of a category of tablets referred to as sulphonylureas instead of taking in insulin. The intake of the drugs has been useful whereby patients who have taken them are viewed to have stayed for more than three years without requiring the injection of insulin (Gardner & Tai 2012, pg. 104). For the GCK, due to the mild hyperglycemia, treatment is not necessary. Treatment only applies during pregnancy whereby insulin is required to limit the excess growth of the fetus. It also applies if the fetus is at risk of acquiring the condition. Due to the progressive nature of the b-cell dysfunction, treatment is necessary for the HNF1A-MODY. The treatment involves low dosages of sulphonylureas; about twelve percent (Gardner & Tai 2012, pg. 104).

What is prediabetes?

Prediabetes implies that the blood sugar level is high when compared to the normal level. However, the level is not high for a person to be diagnosed with Type 2 diabetes (Mayo Clinic 2017, n.p.). When an individual does not make changes in his or her lifestyle, he or she is likely to acquire Type 2 diabetes. An individual with prediabetes is likely to suffer from the damages associated with diabetes particularly when it comes to the kidneys, blood vessels, and the heart. The condition affects both children and adults. The risk factors associated with prediabetes include the presence of diabetes in the family history, race where children from the minority groups are at high risks, low birth weight and being born to a mother infected by gestational diabetes. Nonetheless, it is not necessarily for one to acquire Type 2 diabetes especially developing a healthy lifestyle (Mayo Clinic 2017, n.p.).

What are the diagnostics criteria?

The diagnosis of prediabetes is associated with Glycated hemoglobin (A1C) test. The test is used to determine the average level of blood sugars in an individual after two or three months (Mayo Clinic 2017, n.p.). An A1C level which is below 5.7% is viewed as normal. An A1C level which lies between 5.7% and 6.4% is viewed as prediabetes. An A1C level which shows 6.5% and above after two consecutive tests are viewed as Type 2 diabetes. It is important to note that conditions such hemoglobin imbalance and pregnancy may result in inaccurate results (Mayo Clinic 2017, n.p.).

What is the current consensus of managing prediabetes?

The current consensus of managing prediabetes entails normalizing the levels of glucose and delaying or preventing the development of diabetes and other microvascular complications. The management involves taking part in a therapeutic lifestyle management that includes various modifications of ones lifestyle (Garber et.al. 2008, pg. 934). Some of the modifications include; self-monitoring by the patient, adequate reinforcement, and stimulus control in addition to adequate cognitive strategies. An individual may also take part in Medical Nutrition Therapy (MNT) that includes managing one's weight, appropriate intake of weight, consistency in the daily intake of carbohydrates and limiting the intake of sucrose. Also, physical activity is highly encouraged to reduce the risks of obtaining heart problems (Handelsman et.al. 2015, pg. 3).

References

Anik, A., Catli, G., Abaci, A., & Bober, E., 2015, Maturity-onset diabetes of the young (MODY): an update, Journal of Pediatric and Endocrinal metabolism, 28(3-4), 251-263. doi: 10.1515/jpem-2014-0384.

Garber AJ, Handelsman Y, Einhorn D, Bergman DA, Bloomgarden ZT, Fonseca V, et al. 2008, Diagnosis and management of prediabetes in the continuum of hyperglycemia: when do the risks of diabetes begin? A consensus statement from the American College of Endocrinology and the American Association of Clinical Endocrinologists, Endocrine Practice, 14, 933-46.

Gardner, S.L., & Tai, E.S., 2012, Clinical features and treatment of maturity onset diabetes of the young (MODY), Diabetes Metabolic Syndrome Obesity: Targets and Therapy, 5, 101108.

Handelsman Y, Bloomgarden ZT, Grunberger G, Umpierrez G, Zimmerman RS, Bailey TS, et al., 2015, American Association of Clinical Endocrinologists and American College of Endocrinology: clinical practice guidelines for developing a diabetes mellitus comprehensive care plan, Endocrine Practice, 21, 1-87.

Mayo Clinic (2017). Prediabetes - Diagnosis. [online] Mayo Clinic. Available at: http://www.mayoclinic.org/diseases-conditions/prediabetes/diagnosis-treatment/diagnosis/dxc-20270049 [Accessed 9 Sep. 2017].Pihoker, C. et.al, 2013, Prevalence, Characteristics and Clinical Diagnosis of Maturity Onset Diabetes of the Young Due to Mutations in HNF1A, HNF4A, and Glucokinase: Results From the Search for Diabetes in Youth, The Journal of Clinical Endocrinology and Metabolism, 98(10): 40554062.